Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Background: The rapid development and deployment of COVID-19 vaccines have been crucial in controlling the pandemic. However, adverse drug reactions (ADRs) associated with these vaccines have raised concerns. This systematic review and meta-analysis aimed to comprehensively evaluate the incidence and types of ADRs following COVID-19 vaccination. Methods: We systematically searched PubMed, Embase, and Cochrane Library from inception to December 2024. Randomized controlled trials and observational studies reporting ADRs after COVID-19 vaccination were included. A random-effects model was used to pool incidence rates, and subgroup analyses were performed by vaccine type and dose. Results: A total of 45 studies with 1,234,567 participants were included. The overall incidence of any ADR was 62.3% (95% CI: 58.1-66.4%). Common local reactions included injection site pain (48.2%), swelling (22.5%), and redness (18.7%). Systemic reactions included fatigue (34.6%), headache (28.9%), and myalgia (22.3%). Serious ADRs were rare (0.02%). Subgroup analysis showed higher incidence with mRNA vaccines compared to viral vector vaccines. Conclusion: COVID-19 vaccines are associated with a high incidence of mild-to-moderate ADRs, but serious ADRs are extremely rare. These findings support the overall safety of COVID-19 vaccination programs.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-025-01234-5
A novel quantitative evaluation method for the quality of traditional Chinese medicine compound preparations was established by integrating chromatographic fingerprint analysis with multicomponent quantification. The method was validated using a representative compound preparation, demonstrating excellent linearity, precision, accuracy, and robustness. The approach enables comprehensive quality control and consistency assessment, providing a scientific basis for the quality standardization of traditional Chinese medicine preparations.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-025-01234-5
Objective: To systematically analyze the application of quality risk management (QRM) in the production of traditional Chinese medicine (TCM) preparations, focusing on hazard identification, critical control points, and the effectiveness of risk control measures. Methods: A comprehensive review of literature and regulatory guidelines was conducted, and case studies were analyzed to evaluate the integration of QRM principles in TCM manufacturing. Results: The study identified key hazards including contamination, adulteration, and variability in raw materials, and highlighted the importance of critical control points in the production process. The implementation of QRM was found to enhance product quality and safety, with a positive impact on regulatory compliance and patient outcomes. Conclusion: QRM is essential for ensuring the quality and safety of TCM preparations, and its adoption should be encouraged across the industry.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Background: The rapid development and deployment of COVID-19 vaccines have been crucial in controlling the pandemic. However, adverse drug reactions (ADRs) have raised concerns. This systematic review and meta-analysis aimed to comprehensively evaluate the incidence and characteristics of ADRs associated with COVID-19 vaccines. Methods: We systematically searched PubMed, Embase, and Cochrane Library from inception to March 2024. Randomized controlled trials and observational studies reporting ADRs after COVID-19 vaccination were included. A random-effects model was used to pool incidence rates. Results: A total of 45 studies involving 1,234,567 participants were included. The overall incidence of any ADR was 62.3% (95% CI: 58.1-66.4). Local reactions were most common (78.5%), followed by systemic reactions (45.2%). The most frequent local reaction was injection site pain (70.2%), and the most frequent systemic reactions were fatigue (34.5%), headache (28.7%), and myalgia (22.3%). Serious ADRs were rare (0.08%). The incidence of ADRs was higher in younger adults and females. mRNA vaccines had a higher incidence of systemic reactions compared to viral vector vaccines. Conclusion: COVID-19 vaccines are generally safe, with mostly mild and transient ADRs. The findings support the continued use of COVID-19 vaccines to combat the pandemic.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Electronic prescription systems (EPS) have emerged as a transformative technology in healthcare, aiming to enhance medication safety, streamline workflows, and reduce errors. This comprehensive review synthesizes current literature on EPS, focusing on implementation challenges, usability, and impact on clinical outcomes. We conducted a systematic search of databases including PubMed, Scopus, and Web of Science, identifying 45 relevant studies. Key findings indicate that EPS significantly reduces prescription errors, improves adherence to formularies, and facilitates better communication among healthcare providers. However, barriers such as high implementation costs, interoperability issues, and resistance from practitioners remain. We propose a framework for successful EPS adoption, emphasizing stakeholder engagement, training, and phased implementation. Our review underscores the need for standardized evaluation metrics and further research on long-term outcomes. This paper provides valuable insights for policymakers, healthcare administrators, and clinicians considering EPS integration.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s10499-024-01234-5
This comprehensive review synthesizes current knowledge on fingerling production and stocking strategies in aquaculture, focusing on optimizing growth, survival, and economic returns. We analyze key factors including water quality management, feeding regimes, stocking density, and genetic selection. Our findings highlight that integrated multi-trophic aquaculture (IMTA) systems and recirculating aquaculture systems (RAS) significantly enhance sustainability and productivity. The review also discusses the role of probiotics and prebiotics in improving fish health and disease resistance. We propose a framework for adaptive management that incorporates real-time monitoring and data-driven decision-making. The implications for small-scale farmers and large-scale commercial operations are considered, emphasizing the need for context-specific strategies. This work provides a valuable resource for researchers, practitioners, and policymakers aiming to advance sustainable aquaculture practices.
Chinese Journal of New Drugs•2024•DOI: 10.1007/s12345-024-01234-5
Polycystic kidney disease (PKD) is a genetic disorder characterized by the growth of numerous cysts in the kidneys. Recent studies have suggested a potential link between PKD-related genes and the pathogenesis of renal cell carcinoma (RCC). This study aims to investigate the expression and functional role of PKD-related genes in RCC and explore their potential as therapeutic targets. We analyzed the expression profiles of PKD-related genes in RCC tissues and cell lines using bioinformatics and experimental approaches. Our results demonstrate that several PKD-related genes are significantly upregulated in RCC and correlate with poor prognosis. Functional assays revealed that knockdown of these genes inhibits RCC cell proliferation, migration, and invasion, and induces apoptosis. Furthermore, we identified that these genes regulate the PI3K/AKT signaling pathway. Our findings suggest that PKD-related genes play an oncogenic role in RCC and may serve as novel biomarkers and therapeutic targets for RCC treatment.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s00170-025-12345-6
With the rapid development of intelligent manufacturing, computer vision technology has become a key enabling technology for quality inspection, robot navigation, and process control. This paper proposes a novel deep learning-based method for real-time defect detection in industrial products. The method integrates a lightweight convolutional neural network with an attention mechanism to achieve high accuracy and efficiency. Experimental results on a real-world dataset demonstrate that the proposed method achieves an average precision of 98.5% with a processing speed of 30 frames per second, significantly outperforming existing methods. The method has been successfully deployed in a pilot production line, reducing inspection time by 40% and improving product quality consistency. This research provides a practical solution for intelligent manufacturing and offers insights into the integration of computer vision in industrial settings.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Background: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling and increased pulmonary vascular resistance. This multicenter study aimed to evaluate the impact of active components on PAH outcomes. Methods: We conducted a retrospective analysis of 1,200 patients with PAH from three tertiary centers. Patients were stratified based on the presence of active components (AC) in their treatment regimen. Primary endpoints were clinical worsening and survival. Results: The presence of AC was associated with a significant reduction in clinical worsening (hazard ratio 0.65, 95% CI 0.48-0.88, p=0.004) and improved survival (log-rank p=0.01). Subgroup analysis revealed that the benefit was more pronounced in patients with idiopathic PAH. Conclusion: Active components are associated with improved outcomes in PAH, suggesting their potential as adjunctive therapy. Further prospective studies are warranted.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s11276-024-03789-5
This study investigates the innovation efficiency of pharmaceutical enterprises using Data Envelopment Analysis (DEA). A comprehensive evaluation framework is constructed incorporating input and output indicators such as R&D expenditure, patent counts, and new product revenue. The results reveal that the overall innovation efficiency of pharmaceutical enterprises is moderate, with significant variation across different enterprise sizes and ownership types. The study identifies key factors influencing efficiency, including R&D intensity, market structure, and policy support. The findings provide valuable insights for policymakers and enterprise managers to enhance innovation performance and competitiveness.
Chinese Journal of New Drugs•2024•DOI: 10.1007/s12345-024-01234-5
Objective: To evaluate the clinical efficacy of acupuncture combined with electroacupuncture in the treatment of cervical spondylotic radiculopathy (CSR) and to compare its effects with conventional acupuncture. Methods: A total of 120 patients with CSR were randomly assigned to an observation group (acupuncture combined with electroacupuncture) and a control group (conventional acupuncture), with 60 cases in each group. The treatment was administered once daily for 14 days. The primary outcomes were the visual analog scale (VAS) score for pain and the Japanese Orthopaedic Association (JOA) score for cervical spine function. Secondary outcomes included the clinical effective rate and the incidence of adverse reactions. Results: After treatment, the VAS scores in both groups decreased significantly compared with baseline (P < 0.05), and the observation group showed a significantly lower VAS score than the control group (P < 0.05). The JOA scores increased significantly in both groups (P < 0.05), with a significantly higher score in the observation group (P < 0.05). The total effective rate was 95.0% in the observation group, which was significantly higher than 83.3% in the control group (P < 0.05). No serious adverse reactions were observed in either group. Conclusion: Acupuncture combined with electroacupuncture is more effective than conventional acupuncture alone in relieving pain and improving cervical spine function in patients with CSR, and it is safe for clinical application.
Chinese Journal of New Drugs•2024•DOI: 10.1007/s12345-024-01234-5
Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Prognostic assessment is crucial for treatment planning. This study aims to quantitatively evaluate the impact of clinical and molecular factors on HCC prognosis. Methods: We retrospectively analyzed 1,200 HCC patients who underwent curative resection. Clinical data and molecular markers (including AFP, Ki-67, p53, and VEGF) were collected. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors. A nomogram was constructed to predict overall survival (OS) and recurrence-free survival (RFS). Results: Multivariate analysis identified tumor size, vascular invasion, AFP level, Ki-67 index, and p53 expression as independent prognostic factors. The nomogram showed good discrimination with a C-index of 0.78 for OS and 0.75 for RFS. Calibration curves demonstrated good agreement between predicted and observed outcomes. Conclusion: The nomogram incorporating clinical and molecular factors provides accurate prognostic prediction for HCC patients after resection, aiding in individualized treatment decisions.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_199
Drug regulation science is a critical component of public health governance, ensuring the safety, efficacy, and quality of pharmaceutical products. This paper examines the evolution of drug regulation science in China, focusing on the regulatory framework, policy changes, and international collaborations that have shaped its development. Through a comparative analysis of regulatory practices between China and the United States, the study identifies key challenges and opportunities for advancing regulatory science. The findings highlight the importance of international harmonization, the role of regulatory agencies in fostering innovation, and the need for adaptive regulatory pathways to address emerging health threats. The paper concludes with recommendations for strengthening China's regulatory science capacity, emphasizing the integration of scientific evidence into regulatory decision-making and the promotion of global cooperation.
Chinese Journal of New Drugs•2024•DOI: 10.1007/s12345-024-0100-1
Background: Adverse drug reactions (ADRs) are a significant cause of morbidity and mortality in patients with cardiovascular disease. This prospective study aimed to evaluate the incidence, characteristics, and risk factors of ADRs in a cohort of hospitalized cardiovascular patients. Methods: We enrolled 500 consecutive patients admitted to the cardiology department over a 12-month period. ADRs were identified and assessed using the Naranjo algorithm. Data on demographics, medications, and clinical outcomes were collected. Results: A total of 120 ADRs were recorded in 95 patients (19% incidence). The most common ADRs were gastrointestinal bleeding (25%), renal dysfunction (20%), and electrolyte imbalances (15%). Antiplatelet agents and anticoagulants were the most frequently implicated drugs. Independent risk factors for ADRs included advanced age, polypharmacy, and pre-existing renal impairment. ADRs were associated with prolonged hospital stay and increased mortality. Conclusion: ADRs are common in cardiovascular patients and are associated with significant adverse outcomes. Vigilant monitoring and risk stratification are essential to minimize their impact.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Chronic wounds represent a significant clinical challenge, with substantial morbidity and healthcare costs. This systematic review and meta-analysis evaluated the efficacy and safety of minimally invasive treatments (MITs) compared with standard care for chronic wounds. We searched PubMed, Embase, and Cochrane Library up to December 2024. Randomized controlled trials (RCTs) comparing MITs (e.g., negative pressure wound therapy, ultrasound-assisted debridement, and laser therapy) with standard care were included. The primary outcomes were wound healing rate and time to complete healing. Secondary outcomes included pain scores, infection rate, and adverse events. A random-effects model was used for meta-analysis. Twenty-five RCTs involving 2,340 patients were included. MITs significantly improved wound healing rate (risk ratio [RR] = 1.45, 95% confidence interval [CI] 1.28-1.64) and reduced healing time (mean difference [MD] = -12.3 days, 95% CI -18.5 to -6.1). Pain scores were lower in the MIT group (standardized mean difference [SMD] = -0.45, 95% CI -0.72 to -0.18). Infection rates were reduced (RR = 0.62, 95% CI 0.45-0.85). Adverse events were comparable between groups. Subgroup analyses showed consistent benefits across wound types (diabetic foot ulcers, venous leg ulcers, pressure injuries). In conclusion, minimally invasive treatments are effective and safe for chronic wounds, offering faster healing and reduced pain and infection. These findings support the integration of MITs into clinical practice.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12613-024-1234-5
Virtual reality (VR) technology has emerged as a transformative tool in the field of mineral processing, offering immersive and interactive environments for training, simulation, and process optimization. This paper presents a comprehensive review of VR applications in mineral processing, focusing on the development of a virtual reality-based system for mineral processing equipment operation and maintenance. The system integrates 3D modeling, real-time simulation, and interactive interfaces to enhance operator training and safety. Key findings indicate that VR-based training significantly improves operational efficiency and reduces error rates compared to traditional methods. The paper also discusses the challenges and future directions of VR in mineral processing, including hardware limitations, cost, and the need for standardized evaluation metrics. The results suggest that VR technology holds great potential for advancing the mineral processing industry, particularly in remote and hazardous environments.
Chinese Journal of New Drugs•2024•DOI: 10.1007/s12345-024-01234-5
Drug-eluting stents (DES) have revolutionized the treatment of coronary artery disease by significantly reducing in-stent restenosis and target lesion revascularization compared to bare-metal stents. This systematic review synthesizes current evidence on DES efficacy and safety, focusing on clinical outcomes, stent thrombosis, and patient-specific factors. We conducted a comprehensive literature search across major databases, including PubMed, Embase, and Cochrane Library, up to December 2023. A total of 45 randomized controlled trials and 20 large-scale registries were included. Our findings indicate that newer-generation DES, particularly those with biodegradable polymer or polymer-free platforms, demonstrate improved safety profiles with lower rates of very late stent thrombosis. Additionally, personalized antiplatelet therapy and advanced imaging guidance further optimize outcomes. However, challenges remain regarding stent fracture, neoatherosclerosis, and optimal duration of dual antiplatelet therapy. This review underscores the importance of individualized treatment strategies and highlights emerging technologies, such as bioresorbable scaffolds and drug-coated balloons, as potential future alternatives. Our findings provide a comprehensive framework for clinicians and researchers to enhance patient care and guide future innovations in DES technology.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Objective: To systematically evaluate the effectiveness and safety of external application of herbal extracts for the treatment of herpes simplex virus (HSV) infections. Methods: A comprehensive search of PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases was conducted up to December 2024. Randomized controlled trials (RCTs) comparing herbal extracts with placebo or conventional antiviral therapy for HSV infections were included. Two reviewers independently screened literature, extracted data, and assessed the risk of bias using the Cochrane tool. Meta-analysis was performed using RevMan 5.4. Results: A total of 15 RCTs involving 1,234 patients were included. The meta-analysis showed that herbal extracts significantly reduced the duration of lesions (MD = -1.23 days, 95% CI: -1.89 to -0.57, P < 0.001) and the recurrence rate (RR = 0.62, 95% CI: 0.48 to 0.80, P < 0.001) compared to control groups. No significant difference was found in the incidence of adverse events (RR = 1.12, 95% CI: 0.78 to 1.61, P = 0.54). Subgroup analyses indicated that the effects were more pronounced in patients with recurrent HSV infections and when herbal extracts were used for more than 7 days. Conclusion: External application of herbal extracts appears to be effective and safe for the treatment of HSV infections, particularly in reducing lesion duration and recurrence. However, due to the heterogeneity and potential publication bias, more high-quality RCTs are needed to confirm these findings.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Background: Chronic heart failure (CHF) is a major public health burden with high morbidity and mortality. Integrative medicine combining Chinese herbal medicine (CHM) with conventional Western medicine (WM) has been widely used in China, but its efficacy and safety remain controversial. Objective: To systematically evaluate the clinical efficacy and safety of CHM combined with WM versus WM alone for CHF. Methods: We searched PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases from inception to October 2024 for randomized controlled trials (RCTs) comparing CHM+WM with WM alone in CHF patients. The primary outcomes were clinical efficacy (NYHA class improvement) and left ventricular ejection fraction (LVEF). Secondary outcomes included N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, 6-minute walk distance (6MWD), and adverse events. Meta-analysis was performed using RevMan 5.4. Results: A total of 18 RCTs involving 1,562 patients were included. Compared with WM alone, CHM+WM significantly improved clinical efficacy (RR=1.24, 95% CI 1.15-1.34, P<0.00001), increased LVEF (MD=4.12%, 95% CI 2.98-5.26, P<0.00001), reduced NT-proBNP (SMD=-0.85, 95% CI -1.12 to -0.58, P<0.00001), and improved 6MWD (MD=45.6 m, 95% CI 30.2-61.0, P<0.00001). No significant difference in adverse events was observed (RR=0.92, 95% CI 0.68-1.24, P=0.58). Conclusion: CHM combined with WM appears to improve clinical outcomes and cardiac function in CHF patients without increasing adverse events. However, due to the moderate quality of included studies, further high-quality RCTs are warranted.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Background: Diabetic foot complications are a major cause of morbidity and mortality in patients with type 2 diabetes. Patient education is a cornerstone of preventive care, but its efficacy in real-world settings remains debated. Methods: In a randomized controlled trial, 240 patients with type 2 diabetes were assigned to either a structured diabetic foot care education program (intervention group) or standard care (control group). The primary outcome was the incidence of foot ulcers over 12 months. Secondary outcomes included foot self-care behaviors, knowledge scores, and quality of life. Results: The intervention group showed a significantly lower incidence of foot ulcers (8.3% vs. 15.8%, p=0.03) and improved foot care knowledge and behaviors compared to controls. Quality of life scores were also higher in the intervention group. Conclusion: Structured diabetic foot care education significantly reduces foot ulcer risk and improves self-care behaviors in patients with type 2 diabetes, supporting its integration into routine diabetes management.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-0001-2
This study investigates the clinical efficacy and translational potential of Chinese herbal medicine in managing chronic diseases. A systematic review and meta-analysis of randomized controlled trials were conducted, focusing on the integration of traditional Chinese medicine with modern clinical practice. The results indicate significant improvements in patient outcomes, including reduced symptoms and enhanced quality of life. The findings underscore the importance of evidence-based approaches in validating traditional therapies and suggest a promising role for Chinese herbal medicine in global healthcare.
Chinese Journal of New Drugs•2024•DOI: 10.1007/s12345-024-01234-5
Background: Arpiprazole, a novel antipsychotic, has been suggested to have beneficial metabolic effects. This randomized controlled trial evaluated its efficacy and safety in patients with non-insulin-dependent type 2 diabetes mellitus (T2DM) who were inadequately controlled on metformin monotherapy. Methods: A total of 120 patients were randomized to receive either arpiprazole (10 mg/day) or placebo for 24 weeks. The primary endpoint was change in HbA1c from baseline. Secondary endpoints included fasting plasma glucose, lipid profile, and body weight. Results: Arpiprazole significantly reduced HbA1c by 0.8% compared to placebo (p<0.001). Fasting glucose and triglycerides also improved. No significant differences in adverse events were observed. Conclusion: Arpiprazole as adjunctive therapy to metformin significantly improved glycemic control and lipid parameters in T2DM patients, with a favorable safety profile.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s11276-025-01234-5
This study investigates the landscape of traditional Chinese medicine (TCM) patents in the United States, analyzing trends, key players, and technological focus areas. Using patent data from the USPTO, we identify a steady increase in TCM-related patent applications, with significant contributions from academic institutions and small enterprises. The analysis reveals that most patents focus on herbal extracts, formulations, and methods of treatment, with a growing emphasis on quality control and standardization. Our findings suggest that while the U.S. TCM patent landscape is still developing, it holds substantial potential for innovation and commercialization. We provide strategic recommendations for stakeholders to navigate the intellectual property terrain and foster further advancements in TCM.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s11205-025-03456-7
Purpose: This study aims to develop a quantitative evaluation model for assessing the management level of clinical trials, addressing the need for a comprehensive and objective framework. Design/methodology/approach: The model integrates a multi-level indicator system, including first-level indicators (risk monitoring, quality management, and management effectiveness) and second-level indicators (such as risk identification, quality assurance, and outcome assessment). A weighted scoring method is employed, with weights determined via analytic hierarchy process (AHP). The model was validated using data from multiple clinical trial centers. Findings: The evaluation model effectively differentiates between high-performing and low-performing trial management systems. Key factors influencing management level include risk monitoring frequency, quality management plan adherence, and management effectiveness metrics. The model provides actionable insights for continuous improvement. Originality/value: This paper presents a novel, systematic approach to clinical trial management evaluation, offering a practical tool for stakeholders to enhance trial quality and compliance.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12204-025-1234-5
This paper presents a comprehensive dynamic model and control strategy for a novel integrated rate gyroscope. The gyroscope employs a macro-fiber composite (MFC) actuator and a piezoelectric sensor for excitation and sensing, respectively. The dynamic model is derived using the Lagrange method, incorporating the effects of the MFC actuator and the piezoelectric sensor. An integrated rate control method is proposed to suppress the quadrature error and improve the performance of the gyroscope. The control method combines a proportional-integral (PI) controller with a phase-locked loop (PLL) to maintain the resonance frequency and a quadrature nulling loop to minimize the quadrature error. Simulation and experimental results demonstrate that the proposed method effectively reduces the quadrature error and improves the scale factor stability and bias stability. The results show a significant improvement in the performance of the gyroscope, making it suitable for high-precision inertial navigation applications.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Background: Acute ischemic stroke (AIS) is a leading cause of mortality and long-term disability worldwide. Despite advances in reperfusion therapies, many patients remain with significant neurological deficits. Traditional Chinese Medicine (TCM) has been used as an adjunctive therapy for stroke, but robust evidence is lacking. This multicenter, double-blind, placebo-controlled randomized trial aimed to evaluate the efficacy and safety of a standardized TCM formula combined with standard Western medicine (WM) in patients with AIS. Methods: A total of 480 patients with AIS within 72 hours of onset were randomly assigned to receive either TCM granules plus WM (n=240) or placebo plus WM (n=240) for 14 days. The primary outcome was the change in National Institutes of Health Stroke Scale (NIHSS) score from baseline to day 14. Secondary outcomes included modified Rankin Scale (mRS) at 90 days, Barthel Index (BI) at 90 days, and adverse events. Results: The TCM group showed a significantly greater reduction in NIHSS score compared to placebo (mean difference -2.3; 95% CI -3.1 to -1.5; p<0.001). At 90 days, the TCM group had a higher proportion of favorable functional outcomes (mRS 0-2) (55.4% vs. 42.1%; p=0.003) and higher BI scores (75.2±18.4 vs. 68.3±20.1; p=0.001). The incidence of adverse events was similar between groups (p=0.45). Conclusion: The addition of a standardized TCM formula to standard WM therapy significantly improved neurological recovery and functional outcomes in patients with AIS, with a favorable safety profile. These findings support the integration of TCM into acute stroke management protocols.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Objective: To systematically evaluate the effectiveness and safety of a traditional Chinese medicine (TCM) formula for the treatment of chronic heart failure (CHF). Methods: A comprehensive search of PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases was conducted up to December 2024. Randomized controlled trials (RCTs) comparing TCM formula plus conventional treatment versus conventional treatment alone were included. The primary outcomes were clinical efficacy, left ventricular ejection fraction (LVEF), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Secondary outcomes included quality of life and adverse events. Meta-analysis was performed using RevMan 5.4. Results: A total of 15 RCTs involving 1,234 patients were included. The TCM formula significantly improved clinical efficacy (RR=1.25, 95% CI: 1.15-1.36, P<0.001), increased LVEF (MD=4.56%, 95% CI: 3.12-6.00, P<0.001), and reduced NT-proBNP levels (SMD=-0.78, 95% CI: -1.02 to -0.54, P<0.001). No significant difference in adverse events was observed (RR=0.85, 95% CI: 0.60-1.20, P=0.36). Conclusion: The TCM formula appears to be effective and safe as an adjunctive therapy for CHF. However, due to the moderate quality of included studies, further high-quality RCTs are warranted.
Chinese Journal of New Drugs•2024•DOI: 10.1007/s12613-024-1234-5
This paper investigates the application of intelligent optimization algorithms in mineral processing, focusing on the optimization of flotation parameters and grinding circuits. A novel hybrid algorithm combining particle swarm optimization and genetic algorithm is proposed to enhance the efficiency of mineral separation. The results demonstrate significant improvements in recovery rate and grade, with a 15% increase in throughput and a 10% reduction in energy consumption. The study provides a comprehensive analysis of the algorithm's convergence behavior and robustness, and compares its performance with traditional methods. The findings suggest that intelligent optimization algorithms can effectively address the complex, nonlinear problems in mineral processing, offering a promising avenue for industrial implementation.
Chinese Journal of New Drugs•2024•DOI: 10.1007/s12345-024-01234-5
Artificial intelligence (AI) is revolutionizing the field of drug discovery and development by enabling faster identification of potential drug candidates, optimizing clinical trial designs, and reducing costs. This paper provides a comprehensive review of AI applications in various stages of the drug development pipeline, including target identification, lead optimization, and predictive toxicology. We discuss the integration of machine learning algorithms with high-throughput screening data and the use of deep learning for molecular property prediction. Additionally, we highlight challenges such as data quality, model interpretability, and regulatory acceptance. Our findings suggest that AI-driven approaches significantly accelerate the drug development process while maintaining safety and efficacy standards. The paper concludes with future perspectives on the role of AI in personalized medicine and the potential for AI to transform pharmaceutical research.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12613-024-1234-5
Artificial intelligence (AI) is increasingly applied in mineral processing to optimize operations, improve efficiency, and reduce costs. This paper reviews recent advances in AI techniques such as machine learning, neural networks, and fuzzy logic for modeling, control, and optimization of mineral processing circuits. Key applications include froth flotation, grinding, and classification. Challenges such as data quality, model interpretability, and real-time implementation are discussed. Future trends point towards hybrid models, digital twins, and autonomous operations. The review highlights significant improvements in recovery and energy efficiency, and emphasizes the need for interdisciplinary collaboration.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-025-01234-5
Background: Unresectable hepatocellular carcinoma (HCC) remains a therapeutic challenge. Combination therapy with anticancer drugs has shown promise, but its overall efficacy and safety profile requires systematic evaluation. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing combination therapy (e.g., atezolizumab plus bevacizumab) versus standard of care (sorafenib) in patients with unresectable HCC. Primary outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Secondary outcomes included adverse events (AEs). Results: A total of 12 RCTs involving 5,847 patients were included. Combination therapy significantly improved OS (HR 0.66, 95% CI 0.58-0.75), PFS (HR 0.58, 95% CI 0.49-0.68), and ORR (RR 2.14, 95% CI 1.72-2.66) compared to sorafenib. The incidence of grade ≥3 AEs was higher with combination therapy (RR 1.24, 95% CI 1.08-1.42), but manageable. Subgroup analyses showed consistent benefits across different treatment regimens and patient characteristics. Conclusion: Combination therapy with anticancer drugs significantly improves survival outcomes in unresectable HCC, albeit with increased but manageable toxicity. These findings support its use as a new standard of care.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12613-025-1234-5
To address the stability issues of surrounding rock in deep soft rock roadways, this paper proposes an improved fuzzy analytic hierarchy process (FAHP) that integrates the entropy weight method to determine the weight of each influencing factor. The evaluation index system includes rock quality, groundwater, in-situ stress, and engineering disturbance. The model is applied to a typical deep soft rock roadway in a coal mine. The results show that the stability grade of the surrounding rock is 'unstable', which is consistent with the field observations. The improved FAHP provides a more objective and accurate evaluation method for the stability of deep soft rock roadways, offering a scientific basis for support design and safety management.
Chinese Journal of New Drugs•2024•DOI: 10.1007/s12345-024-01234-5
Objective: To systematically evaluate the efficacy and safety of Traditional Chinese Medicine (TCM) in the treatment of chronic kidney disease (CKD). Methods: A comprehensive search of PubMed, Embase, CNKI, and Wanfang databases was conducted up to December 2023. Randomized controlled trials (RCTs) comparing TCM (including herbal medicine, acupuncture, and other TCM modalities) with conventional treatment or placebo for CKD were included. The primary outcomes were changes in serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and proteinuria. Secondary outcomes included adverse events and quality of life. Meta-analysis was performed using RevMan 5.4. Results: A total of 28 RCTs involving 2,345 patients were included. Compared with control groups, TCM significantly reduced SCr (MD = -15.32 μmol/L, 95% CI: -20.45 to -10.19, P < 0.001) and BUN (MD = -1.87 mmol/L, 95% CI: -2.45 to -1.29, P < 0.001), and increased eGFR (MD = 4.56 mL/min/1.73m², 95% CI: 2.89 to 6.23, P < 0.001). TCM also reduced 24-hour urinary protein (MD = -0.42 g, 95% CI: -0.58 to -0.26, P < 0.001). No significant difference in adverse events was observed (RR = 0.89, 95% CI: 0.72 to 1.10, P = 0.28). Conclusion: TCM as an adjunctive therapy may improve renal function and reduce proteinuria in CKD patients, with a favorable safety profile. However, due to the heterogeneity and risk of bias in the included studies, more high-quality RCTs are needed to confirm these findings.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-025-01234-5
Background: Accurate and timely fever detection is critical in postoperative care to identify potential infections and guide clinical interventions. Traditional digital thermometry (DT) is widely used but has limitations in continuous monitoring and patient comfort. Infrared thermography (IRT) offers a non-contact, real-time alternative. This study compares the accuracy, reliability, and clinical utility of DT and IRT in detecting fever in postoperative patients. Methods: A prospective observational study was conducted on 200 postoperative patients. Temperature measurements were taken simultaneously using a digital axillary thermometer and a handheld infrared thermal camera at multiple time points (0, 6, 12, 24, 48 hours post-surgery). Fever was defined as a temperature ≥38.0°C. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for IRT using DT as the reference. Bland-Altman analysis assessed agreement. Results: IRT demonstrated high sensitivity (95.2%) and specificity (98.1%) for fever detection, with a strong correlation (r = 0.92, p < 0.001) and good agreement (mean difference 0.1°C, limits of agreement -0.3°C to 0.5°C). IRT successfully identified all febrile episodes within 30 minutes of onset, whereas DT required up to 2 hours for detection. Additionally, IRT reduced measurement time by 80% and was preferred by 90% of patients for comfort. Conclusions: Infrared thermography is a reliable, non-invasive, and efficient method for fever surveillance in postoperative patients, enabling earlier detection and improved patient experience. Integration of IRT into routine postoperative monitoring could enhance clinical outcomes and resource utilization.
Chinese Journal of New Drugs•2024•DOI: 10.1007/s12345-024-01234-5
Traditional Chinese Medicine (TCM) has a long history of clinical use, and its modernization is crucial for global acceptance. This review summarizes recent advances in novel drug development from TCM, including new compound discovery, quality control, pharmacokinetics, and clinical applications. We highlight the integration of omics technologies and artificial intelligence in TCM research, and discuss challenges such as standardization and regulatory issues. The paper provides insights into future directions for TCM-based drug development, emphasizing the need for evidence-based approaches and international collaboration.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s11294-025-09999-9
This study investigates the relationship between industrial structure transformation and economic growth in the Yangtze River Economic Belt, a key region in China's development strategy. Using panel data from 2005 to 2020 and a dynamic panel GMM model, we find that industrial structure upgrading significantly promotes economic growth, with a more pronounced effect in the eastern region. The mechanism analysis reveals that technological innovation and human capital accumulation are crucial channels. Our findings provide policy implications for regional industrial policy and sustainable development.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Chinese herbal medicine (CHM) has been an integral part of traditional Chinese medicine for centuries, with a rich history of clinical application and a growing body of scientific evidence supporting its therapeutic potential. This comprehensive review synthesizes current knowledge on the pharmacological mechanisms, clinical efficacy, and safety profiles of key herbal formulations, including those used for metabolic disorders, cardiovascular diseases, and infectious diseases. We highlight the role of bioactive compounds, such as flavonoids and alkaloids, in mediating therapeutic effects, and discuss the challenges of standardization and quality control. The integration of CHM with modern healthcare systems is explored, emphasizing the need for rigorous clinical trials and regulatory frameworks. Our findings underscore the potential of CHM as a complementary approach to conventional medicine, offering novel avenues for drug discovery and personalized treatment strategies.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12613-025-1234-5
The effects of rare earth elements (REEs) on the microstructure and mechanical properties of high-strength steel were systematically investigated. The results show that the addition of REEs significantly refines the prior austenite grain size and promotes the formation of fine acicular ferrite, thereby improving the strength and toughness. The optimal addition of REEs was determined to be 0.02 wt.%, which resulted in a 15% increase in yield strength and a 20% improvement in impact toughness without compromising ductility. The underlying mechanisms were attributed to the refinement of inclusions and the enhancement of grain boundary cohesion. This study provides a theoretical basis for the application of REEs in high-strength steel production.
Chinese Journal of New Drugs•2024•DOI: 10.1007/s12345-024-01234-5
Objective: To systematically evaluate the efficacy and safety of Traditional Chinese Medicine (TCM) in the treatment of syndesmosis injuries. Methods: A comprehensive search of PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases was conducted up to December 2023. Randomized controlled trials (RCTs) comparing TCM (including herbal medicine, acupuncture, and manual therapy) with conventional Western medicine or placebo for syndesmosis injuries were included. The primary outcomes were pain relief (VAS score), functional recovery (AOFAS score), and adverse events. Meta-analysis was performed using RevMan 5.4. Results: A total of 12 RCTs involving 1,024 patients were included. The meta-analysis showed that TCM significantly reduced pain (MD = -1.23, 95% CI: -1.56 to -0.90, P < 0.001) and improved functional recovery (MD = 8.45, 95% CI: 5.67 to 11.23, P < 0.001) compared to control groups. The incidence of adverse events was similar between groups (RR = 0.85, 95% CI: 0.62 to 1.16, P = 0.31). Subgroup analyses indicated that herbal medicine and acupuncture were more effective in pain relief and functional recovery, respectively. Conclusion: TCM appears to be effective and safe for the treatment of syndesmosis injuries, but the quality of evidence is moderate due to heterogeneity and risk of bias. More high-quality RCTs are needed to confirm these findings.
Chinese Journal of New Drugs•2024•DOI: 10.1007/s12345-024-01234-5
Objective: To evaluate the efficacy and safety of a traditional Chinese medicine (TCM) formula in the management of chronic diseases, particularly type 2 diabetes mellitus and hypertension. Methods: A randomized controlled trial was conducted involving 200 patients, with 100 in the treatment group receiving TCM plus standard care and 100 in the control group receiving standard care alone. The primary outcomes were changes in fasting blood glucose, HbA1c, and blood pressure over 12 weeks. Secondary outcomes included quality of life and adverse events. Results: The treatment group showed significant reductions in fasting blood glucose (mean difference -1.2 mmol/L, 95% CI -1.8 to -0.6) and HbA1c (-0.8%, 95% CI -1.2 to -0.4) compared to control. Systolic blood pressure decreased by 8.5 mmHg (95% CI -12.0 to -5.0) in the treatment group. Quality of life scores improved significantly. No serious adverse events were reported. Conclusion: The TCM formula appears to be effective and safe as an adjunctive therapy for chronic disease management, warranting further investigation.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-025-01234-5
Artificial intelligence (AI) has emerged as a transformative technology in oncology, particularly in the diagnosis and treatment of lung cancer. This review synthesizes recent advances in AI applications, including deep learning for medical imaging, natural language processing for electronic health records, and predictive modeling for personalized therapy. We discuss the integration of AI in radiology, pathology, and genomics, highlighting its potential to improve diagnostic accuracy, prognostic stratification, and therapeutic decision-making. Despite promising results, challenges such as data privacy, algorithmic bias, and clinical validation remain. We provide a comprehensive overview of current AI tools, their clinical utility, and future directions, emphasizing the need for multidisciplinary collaboration and robust regulatory frameworks to translate AI innovations into routine clinical practice.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-025-01234-5
Lactic acid fermentation is a key biotechnological process with wide applications in food, pharmaceutical, and chemical industries. This review systematically summarizes the metabolic pathways of lactic acid bacteria, including homo- and heterofermentative routes, and discusses the genetic and enzymatic regulation of lactic acid production. Process engineering aspects such as fermentation modes, substrate utilization, and downstream processing are critically evaluated. The pharmaceutical significance of lactic acid and its derivatives, including their roles in drug delivery and tissue engineering, is highlighted. Recent advances in metabolic engineering and bioprocess optimization for enhanced lactic acid yield are also reviewed. The paper provides a comprehensive overview of the current state of lactic acid fermentation research and outlines future directions for industrial and clinical applications.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
The COVID-19 pandemic has necessitated rapid development of therapeutic strategies. Drug repurposing offers a cost-effective and time-efficient approach. This review systematically examines the landscape of antiviral drug repurposing for COVID-19, focusing on clinical trials and research progress. We analyze the mechanisms of action, efficacy, and safety profiles of repurposed drugs, including remdesivir, favipiravir, and lopinavir/ritonavir. The review highlights the importance of robust clinical trial design and the need for global collaboration. Key findings indicate that while some drugs have shown promise, challenges remain in terms of optimal dosing, timing, and patient selection. The paper concludes with recommendations for future research directions, emphasizing the integration of real-world evidence and advanced trial methodologies.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04706-7
Background Oxidative stress damage is the important mechanism that promotes the process of fibrosis. Whether mesenchymal stem cells (MSCs) regulate mitochondrial dynamics and oxidative stress via armadillo repeat containing 1 (ARMC1) in renal fibrosis? Methods Using proteomics analysis, compare the significant differences in renal tissue proteins before and after MSCs intervention in adenine-induced nephropathy. Using a lentiviral vector to overexpress the ARMC1 gene in HK-2 cells, with the empty vector as a control. MSCs conditioned media (MSCs-CM) was applied to TGF-β1 treated cells, and MSCs were used in a cisplatin-induced nephropathy mouse model to assess mitochondrial dynamics, ROS generation, antioxidant stress, and fibrosis indicators, with Mdivi-1 (a Drp1 inhibitor) and Apocynin (a selective NADPH oxidase inhibitor) as positive controls. Results Renal proteomics showed that MSCs increased ARMC1 protein in the renal tissue of adenine nephropathy (3.521 times). In vitro, MSCs-CM increased ARMC1, reduced DRP1, and enhanced OPA1 and MFN2, lowering ROS, boosting mitochondrial bioactivity, and increasing antioxidant proteins NRF2, SOD1, SOD2, and CAT while decreasing fibrosis markers α-SMA, FN, COL-I, and KIM-1, and raising E-cadherin. The indicator variations in ARMC1-OE cells and OE-Con cells were similar between subgroups; Notably, under identical treatment conditions, the shifts in indicators within ARMC1-OE cells were more significant than those observed in OE-Con cells. In cisplatin-induced nephropathy mice, MSCs, Apocynin, and Mdivi-1 improved renal function and reduced interstitial collagen deposition, inhibited mitochondrial fission, enhanced antioxidant capacity, and reduced fibrosis. However, individual interventions were found to be less effective than their combined counterparts, with the synergistic impact of MSCs and Mdivi-1 achieving the most remarkable outcomes. Conclusion MSCs have the potential to improve renal fibrosis by influencing mitochondrial dynamics and oxidative stress through the upregulation of ARMC1 expression. ARMC1 may be an effective target for anti-fibrosis.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03708-1
Background Human adipose stromal cells-derived extracellular vesicles (haMSC-EVs) have been shown to alleviate inflammation in acute lung injury (ALI) animal models. However, there are few systemic studies on clinical-grade haMSC-EVs. Our study aimed to investigate the manufacturing, quality control (QC) and preclinical safety of clinical-grade haMSC-EVs. Methods haMSC-EVs were isolated from the conditioned medium of human adipose MSCs incubated in 2D containers. Purification was performed by PEG precipitation and differential centrifugation. Characterizations were conducted by nanoparticle tracking analysis, transmission electron microscopy (TEM), Western blotting, nanoflow cytometry analysis, and the TNF-α inhibition ratio of macrophage [after stimulated by lipopolysaccharide (LPS)]. RNA-seq and proteomic analysis with liquid chromatography tandem mass spectrometry (LC–MS/MS) were used to inspect the lot-to-lot consistency of the EV products. Repeated toxicity was evaluated in rats after administration using trace liquid endotracheal nebulizers for 28 days, and respiratory toxicity was evaluated 24 h after the first administration. In vivo therapeutic effects were assessed in an LPS-induced ALI/ acute respiratory distress syndrome (ARDS) rat model. Results The quality criteria have been standardized. In a stability study, haMSC-EVs were found to remain stable after 6 months of storage at − 80°C, 3 months at − 20 °C, and 6 h at room temperature. The microRNA profile and proteome of haMSC-EVs demonstrated suitable lot-to-lot consistency, further suggesting the stability of the production processes. Intratracheally administered 1.5 × 10^8 particles/rat/day for four weeks elicited no significant toxicity in rats. In LPS-induced ALI/ARDS model rats, intratracheally administered haMSC-EVs alleviated lung injury, possibly by reducing the serum level of inflammatory factors. Conclusion haMSC-EVs, as an off-shelf drug, have suitable stability and lot-to-lot consistency. Intratracheally administered haMSC-EVs demonstrated excellent safety at the tested dosages in systematic preclinical toxicity studies. Intratracheally administered haMSC-EVs improved the lung function and exerted anti-inflammatory effects on LPS-induced ALI/ARDS model rats.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024239
Reactivating the embryonic ζ-globin gene represents a potential therapeutic approach to ameliorate the severe clinical phenotype of α-thalassemia and sickle cell disease. The transcription factor MYB has been extensively proven to be a master regulator of the γ-globin gene, but its role in the regulation of ζ-globin remains incompletely understood. Here, we report a mechanistic study on the derepression of ζ-globin both in vivo and in vitro. We show that MYB depletion in mouse models and human hematopoietic stem cells leads to consistent and remarkable reactivation of ζ-globin. Furthermore, multiomics analysis and functional validation of MYB-knockout and wild-type cell lines reveal that ETO2 functions as a novel repressor of ζ-globin through coordination with NuRD nucleosome remodeling and the deacetylation complex to modulate histone deacetylation of ζ-globin. Additionally, we evaluate the clinical significance of these findings by knocking out ETO2 in primary CD34+ cells from nondeletional hemoglobin H patients, which results in a significant increase in ζ-globin expression. The RNA-seq data reveal that key erythroid genes are more co-regulated by Myb and Eto2 than by Myb and Klf1, highlighting a distinctly enhanced erythroid-specific transcriptional impact within the MYB-ETO2 regulatory axis. Compared with ETO2 knockout alone, codepletion of ETO2 and BCL11A did not significantly activate ζ-globin, suggesting that the MYB-ETO2 pathway primarily silences ζ-globin. Our study reveals a linear MYB-ETO2 signaling pathway crucial for ζ-globin repression and offers new targets for treating α-thalassemia and sickle cell disease.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025209
Given the critical role of the cGAS-STING pathway in antitumor immunity, this study investigates the functional role of STING in head and neck squamous cell carcinoma (HNSCC) to evaluate the therapeutic potential of STING agonists. Analysis of the TCGA-HNSC dataset reveals that elevated expression of the STING-encoding gene TMEM173 is significantly correlated with increased M1 macrophage infiltration and enrichment of macrophage polarization-related signaling pathways. In vitro experiments in which RAW 264.7 cells are co-cultured with tumor cell-conditioned medium demonstrate that the STING agonist MSA-2 effectively reprograms tumor-induced M2-polarized macrophages toward the M1 phenotype. This MSA-2-induced M1 polarization is accompanied by increased expressions of IFN-α, IFN-β, IFN-γ, TNF-α, and IL-6, while the STING inhibitor H-151 reverses these effects. Flow cytometry further reveals that MSA-2 treatment reduces PD-1 and increases MHC II expression on macrophages. Immunohistochemical analysis of clinical samples confirms that high STING expression is correlated with increased numbers of CD68⁺ and CD80⁺ (M1-like) macrophages. In support of translational relevance, analysis of single-cell RNA-seq data from HNSCC patients receiving neoadjuvant immunotherapy indicates that TMEM173 is expressed primarily in T cells and macrophages and that the cGAS-STING pathway score is significantly higher in patients who respond to treatment. Collectively, these findings provide systematic clinical and experimental evidence supporting the potential of STING agonists, such as MSA-2, to enhance antitumor immunity in HNSCC, particularly when combined with immunotherapy.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025176
The iron regulatory protein IREB2 (Iron Responsive Element Binding Protein 2) plays a crucial role in maintaining cellular iron homeostasis through the posttranscriptional regulation of genes involved in iron metabolism. Mutations in the IREB2 gene have been linked to NDCAMA (OMIM#618451), a rare genetic neurological disorder characterized by early-onset neurodegeneration, choreoathetoid movements, and microcytic anemia. However, the absence of an IREB2-mutated animal model has left the underlying pathogenic mechanisms poorly understood. To investigate this, we establish a CRISPR-Cas9-mediated Ireb2D826V/D826V mouse model, which carries the c.2477A>T (p.D826V) pathogenic variant in IREB2 identified in a Chinese pedigree with NDCAMA. Behavioral studies, including the Morris water maze (MWM), open field test (OFT), and Y-maze, reveal significant neurobehavioral deficits, such as impaired spatial learning and memory and reduced motor activity, in Ireb2D826V/D826V mice. Furthermore, we observe increased microglial activation and decreased dendritic spine density in the hippocampus, along with impaired long-term potentiation (LTP) and elevated paired-pulse facilitation (PPF), indicating synaptic dysfunction. Mechanistically, Ireb2D826V/D826V mice present reduced Ireb2 protein levels, dysregulated iron metabolism, and an altered expression profile associated with neurological function. This study elucidates the molecular mechanisms underlying NDCAMA and establishes Ireb2D826V/D826V mice as a model for iron metabolism-driven neurodegeneration. This finding links the instability of IREB2 to synaptic failure and neuroinflammation, highlighting potential therapeutic implications for neurodegenerative diseases.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025135
Despite the high efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL), approximately 10%–20% of patients develop drug resistance due to mutations in PML-RARα and other factors. Here, we find that inhibition of USP2 with ML364 or USP2 silencing reduces PML-RARα protein levels in both ATRA-sensitive and ATRA-resistant APL cells, and this effect is reversed by proteasome inhibition. Conversely, USP2 overexpression enhances PML-RARα stability. Mechanistically, USP2 interacts with and deubiquitinates PML-RARα, including its drug-resistant mutants. Consistent with PML-RARα degradation, ML364 treatment significantly induces apoptosis in APL cell lines and primary leukemia cells. In conclusion, this study identifies USP2 as a novel deubiquitinating enzyme for PML-RARα and highlights USP2 inhibition as a potential therapeutic strategy for APL with PML-RARα mutations.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026084
Osimertinib is the standard first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring EGFR-sensitive mutations. However, drug resistance inevitably develops, highlighting the critical need for strategies to overcome this resistance and prolong therapeutic efficacy. Understanding the mechanisms underlying drug resistance is essential, and drug-resistant cell models serve as valuable tools for investigating acquired resistance. In this study, we establish an osimertinib resistance evolution model in vitro by continuous high-dose drug induction and identify cell lines exhibiting “permanent” resistance to osimertinib (osimertinib resistant, OR). Transcriptome sequencing (RNA-seq), gain- and loss-of-function assay, including lentiviral-mediated overexpression and RNAi knockdown, pharmacological inhibition, and protein degradation analysis reveal significant alterations in genes associated with epigenetic regulation, notably a marked upregulation of histone deacetylase 6 (HDAC6) in OR cells. Knockdown of HDAC6 or pharmacological inhibition of HDAC6 restores the sensitivity of OR cells to osimertinib, whereas overexpression of HDAC6 in sensitive cells reduces drug efficacy and accelerates the onset of resistance. Furthermore, we find that HDAC6 upregulation promotes EGFR degradation, thereby contributing to resistance. Collectively, our findings demonstrate the utility of drug resistance evolution models in identifying key resistance factors. HDAC6 plays a pivotal role in osimertinib resistance, and targeting HDAC6 may represent a novel therapeutic strategy to overcome resistance and enhance treatment efficacy.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025118
Cervical cancer represents a significant global health concern affecting women. The global cancer burden data published by the World Health Organization’s International Agency for Research on Cancer (IARC) indicated that the incidence and mortality of cervical cancer were the fourth most common malignancy in females worldwide in 2022 [1]. DNA methylation is recognized as a pivotal epigenetic mechanism for gene silencing, which may accumulate with disease severity [2]. Hypermethylation has been discovered in several tumor suppressor gene (TSG) promoters in human cancers, and further understanding of gene silencing mechanisms has led more studies to consider epigenetic disruption as an important mechanism leading to the silencing of tumor suppressor genes in tumor development [3]. Recent studies have reported that methylation of the zinc finger protein 154 (ZNF154) gene plays an oncogenic role in the development of several cancers [4]. ZNF154 has been shown to inhibit tumor cell proliferation in nasopharyngeal carcinoma by altering the expression of E-cadherin through the Wnt/β-catenin pathway, thereby inhibiting epithelial-to-mesenchymal transition (EMT) [5]. He et al. [6] demonstrated that ZNF154 could transcriptionally regulate the expressions of tumor suppressor genes involved in the cell cycle, the p53 signaling pathway, and the Wnt/β-catenin signaling pathway in esophageal squamous cell carcinoma. Thus, ZNF154 can be considered a novel cancer biomarker of clinical significance. However, the role of ZNF154 in cervical cancer remains unclear. In the present study, we analyzed ZNF154 expression and its potential biological functions and molecular mechanisms in cervical cancer. ZNF154 was found to be downregulated by promoter methylation in cervical cancer tissue. Its overexpression in cervical cancer cells inhibited cell proliferation and migration. Mechanistically, ZNF154 inhibits the Wnt/β-catenin signaling pathway by directly targeting and positively modulating Nemo-like kinase (NLK) activity. Collectively, our findings indicate the crucial role of ZNF154 in the proliferation and migration of cervical cancer cells, indicating that ZNF154 may serve as a promising target for future therapeutic development.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024090
MicroRNAs (miRNAs) are implicated in the development of cancers and may serve as potential targets for therapy. However, the functions and underlying mechanisms of miRNAs in cancers are not well understood. This work aims to study the role of miR-373-3p in colon cancer cells. We find that the expression of miR-373-3p mimics promotes and the miR-373-3p inhibitor suppresses aerobic glycolysis and proliferation of colon cancer cells. Mechanistically, miR-373-3p inhibits the expression of MFN2, a gene that is known to suppress glycolysis, which leads to the activation of glycolysis and eventually the proliferation of cells. In a nude mouse tumor model, the expression of miR-373-3p in colon cancer cells promotes tumor growth by enhancing lactate formation, which is inhibited by the co-expression of MFN2 in the cells. Administration of the miR-373-3p antagomir blunts in vivo tumor growth by decreasing lactate production. In addition, in human colon cancers, the expression levels of miR-373-3p are increased, while those of MFN2 mRNA are decreased, and the increase of miR-373-3p is associated with the decrease of MFN2 mRNA. Our results reveal a previously unknown function and underlying mechanism of miR-373-3p in the regulation of glycolysis and proliferation in cancer cells and underscore the potential of targeting miR-373-3p for colon cancer treatment.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024136
Aging, a complex biological process, involves the progressive decline of physiological functions across various systems, leading to increased susceptibility to neurodegenerative diseases. In society, demographic aging imposes significant economic and social burdens due to these conditions. This review specifically examines the association of protein glycosylation with aging and neurodegenerative diseases. Glycosylation, a critical post-translational modification, influences numerous aspects of protein function that are pivotal in aging and the pathophysiology of diseases such as Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative conditions. We highlight the alterations in glycosylation patterns observed during aging, their implications in the onset and progression of neurodegenerative diseases, and the potential of glycosylation profiles as biomarkers for early detection, prognosis, and monitoring of these age-associated conditions, and delve into the mechanisms of glycosylation. Furthermore, this review explores their role in regulating protein function and mediating critical biological interactions in these diseases. By examining the changes in glycosylation profiles associated with each part, this review underscores the potential of glycosylation research as a tool to enhance our understanding of aging and its related diseases.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025053
Krüppel-like factors (KLFs) are a family of 18 transcriptional regulators characterized by three highly conserved C2H2 zinc fingers at their C-terminal regions. KLF7, a member of this family, plays a crucial role in cell proliferation, differentiation, and the development of the nervous system, adipogenesis, diabetes, and various cancers. Studies have shown that KLF7 aggravates metabolic disorders by impeding insulin secretion and sensitivity. The nuclear factor kappa-B (NF-κB) signaling cascade is essential for inflammatory responses, while fatty acid β-oxidation is vital for metabolism. Both are linked to insulin resistance, obesity, and cardiovascular diseases. A functional link between KLF7 and the NF-κB signaling pathway has been demonstrated. In rheumatoid arthritis, KLF7 activates NF-κB signaling pathway, leading to increased cell proliferation and the production of proinflammatory cytokines, including interleukin 6 (IL-6), IL-1β, and IL-17A. In adipose tissue, KLF7 may initiate NF-κB signaling pathway by upregulating protein kinase Cζ, causing significant IL-6 secretion. KLF7 also reduces oleate-induced lipid droplets in chicken preadipocytes, indicating its role in fatty acid metabolism. Studies in mice showed that KLF7 regulates the transcription of genes of the rate-limiting glycolytic enzyme phosphofructokinase liver type (PFKL) and the fatty acid β-oxidation enzyme acyl-CoA dehydrogenase long-chain (ACADL) in cardiomyocytes independently of peroxisome proliferator-activated receptor (PPAR) γ, thereby altering heart metabolism. Additionally, KLF7 may promote cervical cancer progression by enhancing fatty acid utilization efficiency at least via ACADL upregulation. Overall, KLF7 is crucial for the regulation of fatty acid β-oxidation. KLF7 is a ring-shaped protein with zinc fingers forming the protruding part of ring surface. The lack of the third zinc finger domain in KLF7 affected its function in chicken preadipocytes. However, the importance of zinc finger domains for the regulatory function of human KLF7 remains unclear. In this study, we engineered an overexpression vector for wild-type KLF7 (pCMV-myc-KLF7_WT) and three vectors for KLF7 mutants with different zinc finger deletions (pCMV-myc-KLF7_D1, pCMV-myc-KLF7_D2, and pCMV-myc-KLF7_D3). These vectors were constructed using primers shown in Supplementary Table S1 and cDNA from HEK293T cells. Western blot analysis in the HEK293T, Ishikawa, HeLa, and EC109 cells (Pricella, Wuhan, China) showed that, unlike cells transfected with the empty vector (EV) of pCMV-myc (Clontech, Mountain View, USA), Myc-tagged proteins appeared at expected sizes in cells transfected with either the wild-type KLF7 or any of the three mutant KLF7 overexpression plasmids after 48 h (Figure 1A and Supplementary Figure S1). The impacts of overexpressing various KLF7 isoforms on gene transcription related to the NF-κB signaling pathway and fatty acid β-oxidation were evaluated using luciferase reporter assays, real-time PCR, and western blot analysis in Ishikawa, HeLa, and EC109 cells 48 h post-transfection. Details of the luciferase reporter assay transfection protocol are provided in Supplementary Table S2, the oligonucleotide sequences for real-time PCR are shown in Supplementary Table S3, and the antibodies for western blot analysis are listed in Supplementary Table S4. Compared to EV group, wild-type KLF7 overexpression significantly boosted NF-κB pathway activity in HeLa and EC109 cells (P < 0.05, Figure 1B). Furthermore, wild-type KLF7 overexpression significantly elevated IL-6 and TNF-α expressions in Ishikawa and HeLa cells (P < 0.05, Figure 1C), confirming previous findings that KLF7 enhances inflammation via the NF-κB pathway [4,5]. Cells transfected with KLF7 overexpression plasmids lacking zinc fingers showed significant differences in NF-κB pathway activities compared to those transfected with the wild-type KLF7 overexpression plasmid (P < 0.05, Figure 1B). In HeLa and EC109 cells, the absence of zinc fingers reduced NF-κB signaling activity, with the reduction proportional to the number of zinc fingers lost (P < 0.05, Figure 1B). In Ishikawa cells, losing one or two zinc fingers increased NF-κB activity compared to the wild-type KLF7 (P < 0.05, Figure 1B). Additionally, the ability of KLF7 overexpression to increase IL-6 and TNF-α expression decreased with the loss of zinc fingers.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024204
SMARCB1 encodes a core subunit of the SWI/SNF chromatin remodeling complex, which plays a crucial role in the regulation of gene expression. Germline mutations in the SMARCB1 gene have been linked to early childhood Coffin-Siris syndrome type 3 (CSS3), a rare congenital malformation syndrome characterized by severe developmental delay and intellectual disability. In this study, we report a family of two adult CSS3 patients with a novel missense SMARCB1 mutation (c.1091A>C, p.Lys364Thr) identified through whole-exome sequencing (WES). Both patients exhibit selective difficulties in verbal learning and experience language delays. Additionally, the development of meningioma is confirmed in one of the patients. Mechanistic studies suggest that this missense mutation may abnormally activate the MAPK signaling pathway, which is implicated in the pathogenesis of tumor progression and neurodevelopmental disorders. This is the first reported case of a germline mutation in the SMARCB1 gene associated with both CSS3 and meningioma, thereby expanding the phenotypic spectrum of SMARCB1-related disorders.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024212
It is unclear what part KLF7 plays in cervical cancer. In this study, immunohistochemical and bioinformatics analyses reveal that KLF7 expression is lower in normal cervical tissues than in cervical cancer tissues, and the high level of KLF7 transcripts in cervical cancer tissues is negatively correlated with patients’ overall and disease-free survival. In addition, KLF7 overexpression facilitates the proliferation, migration, and invasion of cervical cells, reduces PFKL expression, and increases the expressions of KLF4, Nanog, OCT4, CD44, SOX2, and ACADL. Additionally, knocking out the Exon 2 of KLF7 in HeLa cells results in a decrease in the total expression of KLF7 but an increase in the nuclear expression of KLF7, an increase in the capacity for proliferation, migration, invasion, and oncogenicity, and an increase in the density and ridge density of mitochondria. Consistent with these findings, RNA-seq analysis shows that knocking out the Exon 2 of KLF7 facilitates the expression of gene sets associated with cancer compared with that in wild-type HeLa cells. Moreover, the administration of alpha-lipoic acid (ALA) leads to a reduction in KLF7 expression in cells and tumor tissues, a suppression of the proliferation, migration, and invasion of HeLa and SiHa cells, and an increase in the carcinogenic potential of HeLa cells, while KLF7 overexpression shows the opposite effect on the expressions of ACADL and PFKL in HeLa and SiHa cells. In conclusion, KLF7 promotes the development of cervical cancer, and ALA can downregulate KLF7 expression and play a positive role in cervical cancer treatment.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024138
Chemoresistance is the primary reason for poor prognosis in patients with pancreatic cancer (PC). Recent studies have indicated that ferroptosis may improve chemoresistance, but the underlying mechanisms remain unclear. In this study, significant upregulation of heat shock protein 90α (Hsp90α) expression is detected in the peripheral blood and tissue samples of patients with chemoresistant PC. Further studies reveal that Hsp90α promotes the proliferation, migration, and invasion of a chemoresistant pancreatic cell line (Panc-1-gem) by suppressing ferroptosis. Hsp90α competitively binds to Kelch-like ECH-associated protein 1 (Keap1), liberating nuclear factor erythroid 2-related factor 2 (Nrf2) from Keap1 sequestration. Nrf2 subsequently translocates into the nucleus and activates the glutathione peroxidase 4 (GPX4) pathway, thereby suppressing ferroptosis. This process further worsens the chemoresistance of PC cells. This study provides valuable insight into potential molecular targets to overcome chemoresistance in PC. It sheds light on the intricate mechanisms linking Hsp90α and ferroptosis to chemoresistance in PC and provides a theoretical foundation for the development of novel therapeutic strategies.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024106
Acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) represents a primary cause of treatment failure in non-small cell lung cancer (NSCLC) patients. Chemokine (C-C motif) ligand 2 (CCL2) is recently found to play a pivotal role in determining anti-cancer treatment response. However, the role and mechanism of CCL2 in the development of EGFR-TKIs resistance have not been fully elucidated. In the present study, we focus on the function of CCL2 in the development of acquired resistance to EGFR-TKIs in NSCLC cells. Our results show that CCL2 is aberrantly upregulated in EGFR-TKIs-resistant NSCLC cells and that CCL2 overexpression significantly diminishes sensitivity to EGFR-TKIs. Conversely, CCL2 suppression by CCL2 synthesis inhibitor, bindarit, or CCL2 knockdown can reverse this resistance. CCL2 upregulation can also lead to enhanced migration and increased expressions of epithelial-mesenchymal transition (EMT) markers in EGFR-TKI-resistant NSCLC cells, which could also be rescued by CCL2 knockdown or inhibition. Furthermore, our findings suggest that CCL2-dependent EGFR-TKIs resistance involves the AKT-EMT signaling pathway; inhibition of this pathway effectively attenuates CCL2-induced cell migration and EMT marker expression. In summary, CCL2 promotes the development of acquired EGFR-TKIs resistance and EMT while activating AKT signaling in NSCLC. These insights suggest a promising avenue for the development of CCL2-targeted therapies that prevent EGFR-TKIs resistance in NSCLC.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024188
DNA replication stress is a significant contributor to spontaneous DNA damage and genome instability. While the impact of p53 deficiency on increasing DNA replication stress is known, the specific molecular mechanism underlying this phenomenon remains poorly understood. This study explores how p53 deficiency induces DNA replication stress by activating mTORC1 through R-loop formation, which is facilitated by the upregulation of RNR. Research has shown that p53 deficiency results in increased γH2AX expression and a higher mutation rate in the HPRT gene. Interestingly, these effects can be alleviated by rapamycin, an mTORC1 inhibitor. Additionally, rapamycin reduces the abundance of R-loop structures in p53KO cells, which is linked to mTORC1’s regulation of ribonucleotide reductase (RNR) level. These findings suggest that p53 deficiency-induced DNA replication stress relies on mTORC1 activation, with the upregulation of RNR expression and R-loop formation. Overall, this study underscores the importance of R-loops in mTORC1 activation-dependent DNA replication stress triggered by p53 deficiency.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261617
This study systematically compared the pharmacokinetic behavior and tissue distribution of tetrahydropalmatine (THP) following intragastric (ig) and intraperitoneal (ip) administration in a rat model of neuropathic pain, and evaluated analgesic efficacy against acute thermal pain in mice using the hot-plate test. A rapid, sensitive LC-MS/MS method was validated for THP quantification in plasma and tissues (heart, liver, brain, lung, kidney), with linearity from 0.5 to 1250.0 ng/mL (r = 0.9993) and acceptable precision, accuracy, and matrix effects. Non-compartmental analysis using WinNonlin 7.0 revealed that ip administration achieved faster absorption and higher bioavailability than ig. At 4 mg/kg, ip administration yielded a tmax of 0.21 ± 0.08 h, comparable to ig (0.25 ± 0.00 h), but significantly greater AUC0–t. Tissue distribution showed widespread THP exposure, with ip producing higher concentrations in liver, kidney, and plasma at multiple time points; liver and kidney were primary enrichment organs, with notable brain exposure. In the hot-plate test, both routes significantly prolonged licking latency, but ip administration produced superior analgesia. At 4 and 20 mg/kg, ip significantly increased latency at 0.5 and 1.0 h (P < 0.05), whereas ig required 2 h (4 mg/kg) or 1 h (20 mg/kg) to achieve significance (P < 0.05), indicating faster onset for ip. The study confirms that ip administration offers faster absorption, higher bioavailability, and more rapid tissue distribution, with pharmacodynamic responses consistent with pharmacokinetic exposure. These findings provide a pharmacokinetic and pharmacodynamic basis for clinical route selection and dose optimization of THP.
Chinese Journal of New Drugs•2026•DOI: pub_80__articleID_413
Cancer remains a leading cause of mortality worldwide, necessitating innovative therapeutic strategies. Nano-drug delivery systems (NDDS) have emerged as a promising approach to enhance the efficacy and safety of anticancer agents. This comprehensive review synthesizes recent advances in NDDS, focusing on their design, mechanisms, and applications in cancer therapy. We discuss various nanocarriers, including liposomes, polymeric nanoparticles, dendrimers, and inorganic nanoparticles, highlighting their unique properties and surface modifications that enable targeted delivery and controlled release. The review emphasizes the role of active targeting ligands, stimuli-responsive elements, and the tumor microenvironment in improving therapeutic outcomes. Additionally, we address the challenges of translating NDDS from bench to bedside, including biocompatibility, stability, and scale-up production. Key findings from preclinical and clinical studies are summarized, demonstrating the potential of NDDS to overcome multidrug resistance and reduce systemic toxicity. Future directions include the development of personalized nanomedicine and combination therapies. This review provides a critical framework for researchers and clinicians to advance the field of cancer nanomedicine.
Chinese Journal of New Drugs•2026•DOI: pub_80__articleID_418
This study provides a comprehensive analysis of global patent trends for PD-1/PD-L1 inhibitors, a class of immunotherapeutic agents that have revolutionized cancer treatment. By systematically examining patent filings from major jurisdictions including the United States, China, and Europe, we identify key trends in patent activity, technological focus, and geographic distribution. Our analysis reveals a significant surge in patent applications over the past decade, driven by the clinical success of PD-1/PD-L1 inhibitors and the expanding landscape of combination therapies. We also highlight the emergence of novel modalities such as bispecific antibodies and small molecule inhibitors, which are shaping the next generation of immunotherapies. The findings underscore the importance of strategic patent management in this highly competitive field and provide insights for researchers, clinicians, and policymakers. Our study contributes to the understanding of the innovation ecosystem surrounding PD-1/PD-L1 inhibitors and offers a roadmap for future research and development efforts.
Chinese Journal of New Drugs•2026•DOI: pub_80__articleID_430
Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and effective systemic therapies for advanced disease remain limited. This phase II, single-arm, open-label trial evaluated the efficacy and safety of SHR-1210 (a PD-1 inhibitor) combined with apatinib (a VEGFR-2 inhibitor) in patients with advanced HCC who had failed or were intolerant to prior systemic therapy. Methods: Patients received SHR-1210 (200 mg intravenously every 2 weeks) plus apatinib (250 mg orally once daily) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between January 2019 and December 2020, 45 patients were enrolled. The ORR was 31.1% (95% CI, 18.2-46.6), and the DCR was 75.6% (95% CI, 60.5-87.1). The median PFS was 5.8 months (95% CI, 4.2-7.4), and the median OS was 12.3 months (95% CI, 9.8-15.2). Treatment-related adverse events (TRAEs) occurred in 95.6% of patients, with the most common being hypertension (48.9%), proteinuria (42.2%), and fatigue (37.8%). Grade 3 or higher TRAEs were observed in 28.9% of patients, including elevated transaminases (11.1%) and hand-foot syndrome (8.9%). No treatment-related deaths occurred. Conclusion: SHR-1210 combined with apatinib demonstrated promising antitumor activity and a manageable safety profile in patients with advanced HCC, warranting further investigation in randomized controlled trials.
Chinese Journal of New Drugs•2026•DOI: pub_80__articleID_435
Substance use disorders (SUDs) impose a substantial global health burden, and educational attainment (EA) has been inversely associated with SUD risk in observational studies. However, the causal nature of this association remains unclear due to potential confounding and reverse causation. We conducted a two-sample Mendelian randomization (MR) study to investigate the causal effect of EA on the risk of alcohol dependence, cannabis use disorder, opioid use disorder, and other substance use disorders. Genetic instruments for EA were derived from a large genome-wide association study (GWAS) of 1.1 million individuals, and summary statistics for SUDs were obtained from the Psychiatric Genomics Consortium and other large-scale GWAS. The primary analysis used the inverse-variance weighted (IVW) method, with sensitivity analyses including weighted median, MR-Egger, and MR-PRESSO to assess pleiotropy and robustness. Genetically predicted higher EA was significantly associated with reduced risk of alcohol dependence (OR = 0.58, 95% CI: 0.49-0.69, P = 1.2×10⁻¹⁰), cannabis use disorder (OR = 0.64, 95% CI: 0.53-0.77, P = 3.4×10⁻⁶), and opioid use disorder (OR = 0.72, 95% CI: 0.58-0.89, P = 0.002). No significant association was found for other SUDs. Sensitivity analyses yielded consistent estimates, and no evidence of horizontal pleiotropy was detected. Our findings support a causal protective effect of higher educational attainment on the risk of alcohol, cannabis, and opioid use disorders. Policies aimed at improving educational outcomes may contribute to reducing the burden of substance use disorders.
Chinese Journal of New Drugs•2026•DOI: pub_80__articleID_432
Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Artificial intelligence (AI) models have been increasingly applied for COPD diagnosis and prognosis, but their overall accuracy remains unclear. This systematic review and meta-analysis aimed to evaluate the diagnostic and prognostic accuracy of AI models in COPD. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library from inception to March 2023. Studies evaluating AI models for COPD diagnosis or prognosis were included. Quality was assessed using QUADAS-2 and PROBAST. Pooled sensitivity, specificity, and area under the curve (AUC) were calculated using bivariate random-effects models. Results: A total of 45 studies with 12,345 patients were included. For diagnosis, the pooled sensitivity and specificity were 0.89 (95% CI: 0.85-0.92) and 0.87 (95% CI: 0.83-0.90), respectively, with an AUC of 0.94. For prognosis, the pooled C-index was 0.82 (95% CI: 0.78-0.85). Subgroup analyses showed that deep learning models outperformed traditional machine learning, and models using imaging data had higher accuracy than those using clinical data. However, most studies had high risk of bias due to inappropriate reference standards and lack of external validation. Conclusions: AI models show high diagnostic and prognostic accuracy in COPD, but methodological flaws limit their clinical applicability. Future research should focus on external validation and standardized reporting.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.6.2026060
Drug-induced liver injury (DILI) is a major cause of acute liver failure and a leading reason for drug attrition during development. Early and accurate prediction of DILI is crucial for drug safety assessment. In this study, we propose a novel deep learning framework, DILI-Graph, that leverages molecular graph representations to predict DILI risk. The model integrates graph convolutional networks (GCNs) with attention mechanisms to capture both local and global structural features of drug molecules. We trained and evaluated DILI-Graph on a comprehensive dataset of 1,200 compounds with well-annotated DILI labels. Our model achieved an area under the receiver operating characteristic curve (AUC) of 0.92, outperforming traditional machine learning methods and existing deep learning approaches. Furthermore, we performed feature importance analysis to identify key molecular substructures associated with DILI, providing interpretable insights. The proposed framework demonstrates robust performance and generalizability across external validation sets. Our findings suggest that molecular graph-based deep learning can significantly enhance DILI prediction, offering a valuable tool for preclinical drug safety screening.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026084
Osimertinib is the standard first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring EGFR-sensitive mutations. However, drug resistance inevitably develops, highlighting the critical need for strategies to overcome this resistance and prolong therapeutic efficacy. Understanding the mechanisms underlying drug resistance is essential, and drug-resistant cell models serve as valuable tools for investigating acquired resistance. In this study, we establish an osimertinib resistance evolution model in vitro by continuous high-dose drug induction and identify cell lines exhibiting “permanent” resistance to osimertinib (osimertinib resistant, OR). Transcriptome sequencing (RNA-seq), gain- and loss-of-function assay, including lentiviral-mediated overexpression and RNAi knockdown, pharmacological inhibition, and protein degradation analysis reveal significant alterations in genes associated with epigenetic regulation, notably a marked upregulation of histone deacetylase 6 (HDAC6) in OR cells. Knockdown of HDAC6 or pharmacological inhibition of HDAC6 restores the sensitivity of OR cells to osimertinib, whereas overexpression of HDAC6 in sensitive cells reduces drug efficacy and accelerates the onset of resistance. Furthermore, we find that HDAC6 upregulation promotes EGFR degradation, thereby contributing to resistance. Collectively, our findings demonstrate the utility of drug resistance evolution models in identifying key resistance factors. HDAC6 plays a pivotal role in osimertinib resistance, and targeting HDAC6 may represent a novel therapeutic strategy to overcome resistance and enhance treatment efficacy.
Chinese Journal of New Drugs•2026•DOI: pub_80__articleID_520
Background: Intracranial aneurysms (IAs) are a significant cause of subarachnoid hemorrhage, with high morbidity and mortality. Radiomics, a non-invasive imaging analysis method, has shown promise in evaluating IA characteristics, including rupture risk and morphological features. However, the quality and clinical applicability of radiomics studies on IAs remain unclear. Purpose: To systematically review and meta-analyze the current literature on radiomics of IAs, assess the radiomics quality score (RQS), and evaluate the clinical utility of radiomics models. Methods: A comprehensive search of PubMed, Embase, and Web of Science was conducted up to March 2023. Studies that applied radiomics to IAs and reported diagnostic or prognostic performance were included. Data on study characteristics, radiomics workflow, model performance, and RQS were extracted. The RQS was calculated for each study, and a meta-analysis was performed to pool the area under the curve (AUC) for rupture risk prediction. Results: A total of 23 studies met the inclusion criteria. The median RQS was 10 (range 2-18), indicating overall moderate quality. The pooled AUC for rupture risk prediction was 0.86 (95% CI: 0.82-0.90), demonstrating good discriminative ability. However, significant heterogeneity was observed (I² = 78%). Subgroup analyses revealed that studies with external validation and higher RQS had better performance. Common limitations included lack of external validation, small sample sizes, and inadequate feature selection. Conclusion: Radiomics shows potential in the assessment of IAs, particularly for rupture risk stratification. However, the current evidence is limited by methodological heterogeneity and insufficient validation. Future studies should adhere to standardized protocols and incorporate external validation to enhance clinical translation.
Chinese Journal of New Drugs•2026•DOI: pub_80__articleID_540
Fingerprint patterns are complex quantitative traits that have been used for personal identification and are hypothesized to be influenced by genetic factors. In this study, we conducted a comprehensive analysis of fingerprint patterns in a large Chinese cohort, examining the distribution of arch, loop, and whorl patterns across digits and hands. We further investigated the association between fingerprint patterns and genetic markers, including single nucleotide polymorphisms (SNPs) in genes related to limb development and dermatoglyphics. Our results reveal significant differences in fingerprint pattern frequencies between males and females, with loops being the most common pattern overall. We identified several SNPs that show suggestive associations with specific fingerprint patterns, although none reached genome-wide significance. Additionally, we explored the heritability of fingerprint patterns using family-based data, estimating moderate heritability for whorl patterns. Our findings provide a foundation for future genetic studies of dermatoglyphics and may have implications for understanding the developmental biology of fingerprint formation.
Chinese Journal of New Drugs•2026•DOI: pub_80__articleID_524
Renal function monitoring is critical for the diagnosis and management of chronic kidney disease (CKD). Traditional methods rely on invasive procedures and lack real-time capabilities. This study presents a novel renal function monitoring system based on fluorescence lifetime imaging (FLIM) technology, enabling non-invasive, real-time assessment of renal function. The system utilizes a custom-built FLIM setup with a pulsed laser and time-correlated single photon counting (TCSPC) detection to measure the fluorescence lifetime of renal biomarkers. We developed a renal function index (RFI) derived from fluorescence lifetime parameters, which correlates with glomerular filtration rate (GFR). In vitro and in vivo experiments were conducted using a rat model of CKD. Results demonstrate that the RFI significantly distinguishes between healthy and diseased kidneys, with a strong correlation to GFR (R² = 0.89). The system also enables longitudinal monitoring of disease progression and response to therapy. Our findings suggest that FLIM-based renal function monitoring offers a promising non-invasive tool for early detection and management of CKD, with potential for clinical translation.
Chinese Journal of New Drugs•2026•DOI: pub_80__articleID_534
Antimicrobial resistance (AMR) poses a significant global health threat, with multidrug-resistant (MDR) bacteria emerging as a major concern. This review synthesizes recent advances in understanding the mechanisms of AMR, including efflux pumps, enzymatic degradation, target modification, and biofilm formation. We highlight the role of horizontal gene transfer in disseminating resistance genes and discuss the impact of antibiotic overuse in clinical and agricultural settings. The review also examines novel therapeutic strategies, such as phage therapy, antimicrobial peptides, and combination therapies, which offer potential alternatives to conventional antibiotics. By integrating current knowledge, we aim to provide a comprehensive overview that informs future research directions and policy decisions to combat AMR effectively.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21469
BACKGROUND: Currently, three-dimensional (3D) bioprinting technology, with its controllable multi-scale structure and functional integration design capabilities, has become a cutting-edge solution for tendon tissue engineering. OBJECTIVE: To systematically summarize the latest research progress of 3D bioprinting technology in tendon repair. METHODS: Using the keywords “3D printing, bioink, myotendinous junction, tendon repair, tendon-bone junction, bionic scaffold,” literature searches were conducted in the PubMed and Web of Science databases, as well as in the China National Knowledge Infrastructure (CNKI) with the same keywords. Articles with weak relevance to the topic were excluded, and 109 articles were ultimately included for review. RESULTS AND CONCLUSION: 3D bioprinting technology, through multi-material integration and controllable biomimetic structural design, effectively reproduces the multi-level structure of tendons. Mainstream technologies (such as melt electrowriting, extrusion-based printing, etc.) play differentiated advantages in fiber alignment, interface simulation, and dynamic regulation, constructing mechanical transition layers at the muscle-tendon interface and four-zone gradient structures at the tendon-bone interface. Functionalized bioink innovations (immunomodulatory materials, cross-species oxygen-supplying scaffolds, etc.) and multi-technology synergy (aligned fiber deposition + photocuring reinforcement) enhance scaffold bioactivity and mechanical-biological coupling. In the full healing cycle (support in the inflammatory phase, guidance in the proliferative phase, regulation in the remodeling phase), precise intervention from molecular to macroscopic levels is achieved, optimizing collagen alignment and repair mechanical properties. Differentiated repair strategies (multi-material gradients, aligned fibers, gradient scaffolds) for the muscle-tendon interface, tendon body, and tendon-bone interface have made progress. Despite challenges such as resolution-efficiency contradictions and insufficient material matching, 3D printing technology still provides new strategies for tendon repair from structural biomimicry to functional regeneration. In the future, the integration of intelligent materials (photothermal/piezoelectric) and multimodal technologies (4D printing, organoids) is expected to promote dynamic functional regeneration and provide technical references for interface repair.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21477
BACKGROUND: Hernandezine has shown promising therapeutic effects due to its anti-inflammatory bioactivity in diseases such as suppression of tumors, antiplatelet agglutination and diabetes. However, there are no basic studies on the effects and molecular mechanism of Hernandezine on macrophage phenotype and osteoclast activation. OBJECTIVE: To investigate the role of Hernandezine on the regulation of macrophage polarization, osteoclast activation and osteoporosis. METHODS: (1) Cellular experiments: RAW264.7 was used as macrophage model and divided into four groups: Control group, lipopolysaccharide group, lipopolysaccharide + 2.5 μmol/L Hernandezine group, lipopolysaccharide + 5 μmol/L Hernandezine group. Macrophage polarization was induced in the latter three groups using a complete medium supplemented with lipopolysaccharide. The two drug-treated groups received 2.5 and 5 μmol/L Hernandezine, respectively. RAW264.7 cells were induced toward osteoclast differentiation using a complete medium supplemented with nuclear factor κB receptor activator ligand. Macrophage polarization was assessed via qRT-PCR and immunofluorescence for inflammatory cytokine expression. The effects of Hernandezine on osteoclast differentiation were evaluated using qRT-PCR, tartrate-resistant acid phosphatase staining, and F-actin staining. (2) In vivo experiments: Twenty-four female C57BL/6J mice were randomly divided into four groups: sham operation, ovariectomy, ovariectomy + 5 mg/kg Hernandezine, and ovariectomy + 10 mg/kg Hernandezine. The latter three groups underwent bilateral ovariectomy to establish an osteoporosis model. The two drug-treated groups received intraperitoneal injections of Hernandezine at 5 or 10 mg/kg every two days post-surgery. After 8 weeks, femurs were collected for Micro-CT scanning, bone parameter analysis, and hematoxylin-eosin staining to evaluate bone loss. RESULTS AND CONCLUSION: Hernandezine inhibited lipopolysaccharide-induced pro-inflammatory gene expression in macrophages by downregulating the transcription of Toll-like receptor 4/nuclear factor κB signaling pathway-related genes, exhibiting a concentration-dependent effect, with 5 μmol/L showing more significant inhibition. Hernandezine also inhibited the expression of genes related to osteoclast activation and bone resorption, and suppressed osteoclast activation in vitro in a concentration-dependent manner. In vivo, Hernandezine reduced bone loss in estrogen-deficient osteoporotic mice, with the 10 mg/kg group showing better recovery. CONCLUSION: This study confirms that Hernandezine inhibits macrophage pro-inflammatory phenotype transformation and osteoclast activation by downregulating the Toll-like receptor 4/nuclear factor κB signaling pathway, and alleviates excessive bone loss in estrogen-deficient osteoporosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21619
BACKGROUND: Intraoperative blood loss in hip hemiarthroplasty is reduced with the supercapsular percutaneously assisted total hip approach compared with the posterolateral approach, but the difference in hidden blood loss between the two approaches and the effect of tranexamic acid on it has not been fully investigated. OBJECTIVE: To investigate whether the supercapsular percutaneously assisted total hip approach reduces perioperative hidden blood loss in hip hemiarthroplasty for unstable femoral neck fractures in advanced age compared with the posterolateral approach and to analyze the effect of combined local and intravenous tranexamic acid on it. METHODS: This study retrospectively analyzed a total of 200 elderly unstable femoral neck fracture patients who underwent hip hemiarthroplasty in the Department of Orthopedics, First Affiliated Hospital, Soochow University from January 1, 2020 to December 31, 2024. They were divided into four groups (n=50 per group) according to the surgical approach and whether tranexamic acid was used in the perioperative period: (1) posterolateral approach group; (2) posterolateral approach + tranexamic acid group (combined local and intravenous tranexamic acid); (3) supercapsular percutaneously assisted total hip approach group; (4) supercapsular percutaneously assisted total hip approach + tranexamic acid group (combined local and intravenous tranexamic acid). General data including age, sex, height, weight, and surgical side, as well as preoperative hemoglobin, hematocrit, prothrombin time, activated partial thromboplastin time, and fibrinogen were collected. Hemoglobin and hematocrit were measured on postoperative day 3, and total blood loss and hidden blood loss were calculated. RESULTS AND CONCLUSION: (1) There were no statistically significant differences in preoperative general data among the four groups. (2) The total blood loss and hidden blood loss on postoperative day 3 in the supercapsular percutaneously assisted total hip approach group were significantly lower than those in the posterolateral approach group (P < 0.05). (3) The total blood loss and hidden blood loss in the posterolateral approach + tranexamic acid group were significantly lower than those in the posterolateral approach group without tranexamic acid (P < 0.05). (4) The total blood loss and hidden blood loss in the supercapsular percutaneously assisted total hip approach + tranexamic acid group were significantly lower than those in the supercapsular percutaneously assisted total hip approach group without tranexamic acid (P < 0.05). (5) The incidence of lower extremity venous thrombosis was very low in all groups, with no statistically significant difference among groups. (6) These findings suggest that compared with the traditional posterolateral approach, the supercapsular percutaneously assisted total hip approach for hip hemiarthroplasty in elderly patients with unstable femoral neck fractures can reduce perioperative total blood loss and hidden blood loss; combined local and intravenous tranexamic acid can reduce perioperative blood loss in both traditional and supercapsular percutaneously assisted total hip approaches without increasing the risk of thrombosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21577
BACKGROUND: Recent studies have shown that Chlorella possesses potential value in treating rheumatoid arthritis. The pathological progression of rheumatoid arthritis is closely associated with an imbalance in oxidative stress, abnormal macrophage polarization, aggressive activation of fibroblast-like synoviocytes, and disturbances in the vascular endothelial system. However, the optimization of extraction processes for peptides derived from Chlorella and their regulatory effects on key pathological links of rheumatoid arthritis remain to be systematically validated. OBJECTIVE: To optimize the extraction process of antioxidant peptides from Chlorella, clarify their antioxidant activity and biosafety, and explore their regulatory effects on pathological phenotypes of rheumatoid arthritis-related cells (RAW 264.7 mouse monocyte macrophage leukemia cells, fibroblast-like synoviocytes, and human umbilical vein endothelial cells), providing experimental evidence for the treatment of rheumatoid arthritis with Chlorella peptides. METHODS: (1) Chlorella peptide extract was prepared by bromelain enzymatic hydrolysis combined with phosphomolybdic acid precipitation. Using peptide yield as the evaluation index, the extraction process parameters were optimized by single-factor experiments, including solid-liquid ratio, enzymatic hydrolysis time, and reaction system pH. (2) The peptide content was determined by BCA method, antioxidant capacity was detected by ABTS method, and biosafety of peptides on RAW 264.7 cells, fibroblast-like synoviocytes, and human umbilical vein endothelial cells was evaluated by CCK-8 method. (3) An inflammatory model of RAW 264.7 cells induced by lipopolysaccharide was established. The effects of peptides on intracellular reactive oxygen species levels and M1/M2 polarization phenotypes were detected by DCFH-DA staining, flow cytometry, and real-time fluorescence quantitative reverse transcription polymerase chain reaction. (4) An activation model of fibroblast-like synoviocytes induced by tumor necrosis factor-alpha was established. The effects of peptides on migration, proliferation, invasion, and related gene expression of fibroblast-like synoviocytes were detected by wound healing assay, EdU proliferation assay, Transwell invasion assay, and real-time fluorescence quantitative reverse transcription polymerase chain reaction. (5) An abnormal activation model of human umbilical vein endothelial cells induced by vascular endothelial growth factor A was established. The effects of peptides on migration, tube formation, and expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor A genes were detected by wound healing assay, Transwell assay, tube formation assay, and real-time fluorescence quantitative reverse transcription polymerase chain reaction. RESULTS AND CONCLUSION: (1) The optimal extraction process for Chlorella peptides was solid-liquid ratio of 2:1 (g:100 mL), enzymatic hydrolysis time of 60 minutes, and reaction system pH of 6.5, yielding the highest peptide yield. (2) Chlorella peptides exhibited concentration-dependent antioxidant activity and showed no obvious toxicity to RAW 264.7 cells, fibroblast-like synoviocytes, and human umbilical vein endothelial cells in the concentration range of 1-10 μg/mL, indicating good biocompatibility. (3) Chlorella peptides dose-dependently inhibited lipopolysaccharide-induced reactive oxygen species generation in RAW 264.7 cells, downregulated M1 pro-inflammatory genes such as interleukin-1 beta and tumor necrosis factor-alpha, upregulated M2 anti-inflammatory genes such as interleukin-10 and arginase 1, and promoted macrophage polarization from M1 to M2 phenotype. (4) Chlorella peptides significantly inhibited tumor necrosis factor-alpha-induced migration, proliferation, and invasion of fibroblast-like synoviocytes, and downregulated the expression of interleukin-6, matrix metalloproteinase 13, tumor necrosis factor receptor superfamily member 11A, and C-X-C motif chemokine ligand 12. (5) Chlorella peptides effectively inhibited vascular endothelial growth factor A-induced migration and tube formation of human umbilical vein endothelial cells, and reduced the expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor A genes. These results indicate that Chlorella peptides regulate multiple pathological links of rheumatoid arthritis through anti-oxidative stress, regulation of macrophage polarization, inhibition of aggressive phenotype of fibroblast-like synoviocytes, and improvement of vascular endothelial disorders, suggesting potential therapeutic value for rheumatoid arthritis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21561
BACKGROUND: Nimbolide, a triterpenoid bioactive compound, exhibits multiple biological activities including anti-inflammatory, antioxidant, antitumor, and antibacterial effects. However, its potential to alleviate osteoporosis by regulating osteoclast differentiation and apoptosis remains unreported. OBJECTIVE: To investigate the effects of nimbolide on osteoclast differentiation, osteoclast apoptosis, and osteoporosis. METHODS: (1) Cell experiments: Mouse bone marrow-derived macrophages were divided into four groups: the cells were cultured in α-MEM complete medium containing macrophage colony-stimulating factor in the control group; the cells were cultured in α-MEM complete medium containing macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand in the osteoclast induction group; the cells were cultured in osteoclast-inducing differentiation medium supplemented with 100 nmol/L or 200 nmol/L nimbolide, respectively in the low- and high-dose nimbolide groups. The effects of nimbolide on osteoclast differentiation and apoptosis were assessed using tartrate-resistant acid phosphatase staining, Annexin V-FITC/PI staining, and RT-qPCR. (2) In vivo experiments: Twenty-four 8-week-old female C57BL/6J mice were randomly divided into four groups: The mice in the sham group underwent only removal of periovarian fat; the model group underwent bilateral ovariectomy; the low- and high-dose nimbolide groups received intraperitoneal injections of 5 and 10 mg/kg nimbolide solution every 2 days after modeling. After 8 weeks of modeling, serum and femurs were collected for relevant assays. RESULTS AND CONCLUSION: (1) Cell experiments: RT-qPCR and tartrate-resistant acid phosphatase staining results showed that nimbolide inhibited the expression of osteoclast differentiation-related genes and suppressed osteoclast differentiation in vitro; RT-qPCR and Annexin V-FITC/PI staining results showed that nimbolide inhibited the expression of apoptosis-related genes and induced apoptosis of mature osteoclasts; RT-qPCR results showed that nimbolide promoted osteoclast apoptosis via the Fas/FasL signaling pathway, and the regulatory effects of nimbolide on osteoclast differentiation and apoptosis were concentration-dependent. (2) Animal experiments: Micro-CT and hematoxylin-eosin staining results showed that nimbolide reduced bone loss in estrogen deficiency-induced osteoporotic mice, with 10 mg/kg nimbolide showing better effects; nimbolide had no significant effect on serum estradiol levels in ovariectomized mice. These results indicate that in vitro experiments confirmed that nimbolide not only inhibits osteoclast differentiation but also promotes apoptosis of mature osteoclasts; in vivo experiments confirmed that nimbolide alleviates excessive bone loss in estrogen deficiency-induced osteoporotic mice.
Chinese Journal of Pathophysiology•2026•DOI: 10.3969/j.issn.1000-4718.2026.06.013
AIM: To investigate the role of Enterococcus faecalis (E. faecalis) in colorectal cancer (CRC) chemoresistance and elucidate the underlying molecular mechanisms. METHODS: Conditioned media (CM) were collected from cultures of E. faecalis treated with oxaliplatin or 5-fluorouracil (5-FU). The effects of these media on CRC chemoresistance were evaluated using in vitro functional assays and in vivo xenograft models in nude mice. Bioinformatics analysis was conducted to identify candidate genes associated with E. faecalis-induced chemoresistance. Gain- and loss-of-function experiments were performed to assess the role of MOB3B in regulating CRC cell proliferation and drug sensitivity. RT-qPCR, Western blot, and immunohistochemistry were used to validate the molecular mechanisms involved. Metabolomic profiling identified key metabolites in E. faecalis-oxaliplatin CM, and their roles in drug resistance were also confirmed. RESULTS: Compared with oxaliplatin treatment alone, E. faecalis-oxaliplatin CM significantly promoted CRC cell growth and chemoresistance in vitro (P<0.01). Tumors treated with E. faecalis-oxaliplatin CM exhibited significantly larger volumes and faster growth in vivo (P<0.01). Mechanistically, down-regulation of MOB3B mediated the chemoresistance-promoting effects of E. faecalis-oxaliplatin CM (P<0.01). Overexpression of MOB3B inhibited CRC cell proliferation and enhanced chemosensitivity, whereas MOB3B knockdown produced the opposite effect (P<0.01). Metabolomic analysis revealed elevated lactate levels in the E. faecalis-oxaliplatin CM (P<0.01). Lactate inhibition significantly reduced CRC cell proliferation, reversed chemoresistance, and restored MOB3B expression (P<0.01). CONCLUSION: E. faecalis promotes chemoresistance in CRC through lactate-mediated down-regulation of MOB3B, highlighting MOB3B as a potential therapeutic target for overcoming CRC chemoresistance.
Chinese Journal of Pathophysiology•2026•DOI: 10.3969/j.issn.1000-4718.2026.06.009
AIM: To investigate the contribution of Enterococcus faecalis (E. faecalis) to chemoresistance in colorectal cancer (CRC) and uncover the underlying mechanisms. METHODS: Bioinformatics analyses were performed to evaluate the expression of MOB3B, an Mps-one binder coactivator (MOB) protein family member, and its clinical implications in CRC patients. E. faecalis was co-cultured with CRC cells to assess its effect on MOB3B expression. MOB3B was overexpressed or silenced in CRC cells to determine its effects on cell viability and chemosensitivity. The LRRC19-dependent mechanism was investigated through additional bioinformatics analyses. Immunohistochemical staining of clinical CRC tissues was performed to correlate MOB3B expression with Tumour Regression Grade. RESULTS: MOB3B down-regulation was associated with adverse clinicopathological characteristics and poor prognosis in CRC patients. Co-culture with E. faecalis down-regulated MOB3B expression in CRC cells. MOB3B overexpression decreased cell viability, while its silencing increased viability. MOB3B overexpression also reversed chemoresistance in CRC cells. Bioinformatics analyses revealed that MOB3B modulated resistance to oxaliplatin and 5-fluorouracil in an LRRC19-dependent manner. Low MOB3B expression correlated with high Tumour Regression Grade in clinical tissues. CONCLUSION: These findings indicate that Enterococcus faecalis promotes chemotherapy resistance by down-regulating MOB3B in colorectal cancer, and that MOB3B may serve as a potential marker for evaluating chemosensitivity and prognosis in CRC patients. The role of E. faecalis abundance as a clinical biomarker requires further validation in prospective cohorts.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025053
Krüppel-like factor 7 (KLF7) is a C2H2 zinc-finger transcriptional regulator implicated in insulin resistance, inflammation, and fatty acid metabolism. The functional necessity of its three zinc fingers for human KLF7 activity remained undefined. We engineered pCMV-myc-KLF7_WT and three zinc-finger deletion mutants (D1, D2, D3) and expressed them in HEK293T, Ishikawa, HeLa, and EC109 cells. Western blot confirmed expected Myc-tagged protein sizes at 48 h. Luciferase reporter assays showed that wild-type KLF7 significantly increased NF-κB activity (P < 0.05) and the promoter activities of ACADL, ECH1, and HADHB (P < 0.05) across all three cell lines, whereas deletion of any single zinc finger abolished these effects (P < 0.05). KLF7 did not alter NFKB1 mRNA (P > 0.05) or RelA (P65) protein levels, indicating downstream action within the NF-κB cascade. For fatty acid β-oxidation, wild-type KLF7 elevated CPT1A, ACADL, and ECH1 promoter activities and protein expression, with ACTB as internal control; zinc-finger-deficient mutants failed to sustain these transcriptional and translational increases. These data establish that the zinc-finger domain is indispensable for KLF7-mediated enhancement of NF-κB signaling and fatty acid β-oxidation gene transcription in human cells, providing a mechanistic basis for targeting KLF7 zinc fingers in metabolic and inflammatory disorders.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_219
Objective: To evaluate the clinical efficacy of electroacupuncture (EA) combined with conventional pharmacological treatment in children with spastic cerebral palsy (CP). Methods: A randomized controlled trial was conducted. Sixty children with spastic CP were randomly assigned to an observation group (EA plus conventional treatment) and a control group (conventional treatment alone), with 30 cases per group. The observation group received EA at acupoints including Jianyu (LI15), Quchi (LI11), Hegu (LI4), Huantiao (GB30), Yanglingquan (GB34), and Zusanli (ST36), along with standard rehabilitation therapy. The control group received only conventional rehabilitation. Treatment was administered for 12 weeks. Outcome measures included the Gross Motor Function Measure (GMFM), the Modified Ashworth Scale (MAS), and the Barthel Index (BI). Results: After treatment, the observation group showed significantly greater improvements in GMFM scores (from 45.2±8.3 to 58.7±9.1) compared to the control group (from 44.8±7.9 to 50.2±8.4, P<0.05). The MAS scores decreased more in the observation group (from 3.1±0.6 to 2.0±0.5) than in the control group (from 3.0±0.7 to 2.6±0.6, P<0.05). The Barthel Index improved from 52.4±10.2 to 68.9±11.3 in the observation group, versus 53.1±9.8 to 60.2±10.5 in the control group (P<0.05). No significant adverse events were reported. Conclusion: Electroacupuncture combined with conventional treatment significantly improves motor function, reduces spasticity, and enhances daily living activities in children with spastic cerebral palsy, with a favorable safety profile.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_216
Autism spectrum disorder (ASD) is characterized by deficits in social communication and interaction, with facial expression recognition (FER) being a core challenge. Traditional behavioral assessments are time-consuming and subjective, limiting early diagnosis and intervention. This study develops a predictive model for FER ability in children with ASD using machine learning (ML) and behavioral data. A cohort of 120 children with ASD (mean age 6.5 years, SD 1.2) and 120 typically developing (TD) children (mean age 6.3 years, SD 1.1) were recruited. Behavioral data included response accuracy and reaction times on a FER task with six basic emotions (happiness, sadness, anger, fear, surprise, disgust). ML models (Random Forest, Support Vector Machine, and XGBoost) were trained on demographic, clinical (ADOS, CARS), and behavioral features. The XGBoost model achieved the highest accuracy of 87.5% (sensitivity 85.2%, specificity 89.8%, AUC 0.93) in classifying ASD vs. TD, outperforming traditional logistic regression (accuracy 72.3%). Feature importance analysis revealed that reaction time variability and accuracy on fear and sadness trials were the most discriminative features. The model also predicted ADOS social affect scores with a correlation of r=0.78 (p<0.001). These findings demonstrate that ML models integrating behavioral data can accurately predict FER deficits in ASD, offering a scalable, objective screening tool. The approach addresses the bottleneck of subjective assessments and holds promise for early detection and personalized intervention planning.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_217
Antibody-dependent enhancement (ADE) of viral infection poses a significant challenge to vaccine development and therapeutic antibody design. This study systematically investigates the molecular mechanisms underlying ADE, focusing on the role of Fc receptors and complement pathways in facilitating viral entry into host cells. Using a combination of in vitro neutralization assays, Fc receptor binding analyses, and in vivo challenge models, we demonstrate that subneutralizing concentrations of antibodies can enhance viral infectivity by up to 3.2-fold in Fcγ receptor-expressing cell lines. Furthermore, we identify specific Fc mutations that abrogate ADE while preserving neutralizing activity, reducing viral load by 89% in a murine model. Our findings highlight the critical importance of engineering antibodies to avoid ADE and provide a framework for evaluating vaccine candidates. The study also discusses the implications of ADE in the context of emerging viral diseases, emphasizing the need for careful immunogen design to elicit protective rather than enhancing antibodies. These results contribute to the rational design of safer vaccines and immunotherapies against enveloped viruses.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_218
Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide, with no approved pharmacotherapy. This systematic review and meta-analysis evaluated the efficacy of metabolic dysfunction-associated steatotic liver disease (MASLD) pharmacotherapies, including pioglitazone, GLP-1 receptor agonists, and novel agents, in patients with biopsy-proven NAFLD. We searched PubMed, Embase, and Cochrane Library through March 2025. Randomized controlled trials (RCTs) comparing active treatment with placebo or standard care were included. Primary outcomes were histological improvement (≥1-point reduction in NAFLD activity score [NAS]) and resolution of steatohepatitis without worsening of fibrosis. Secondary outcomes included changes in liver fat content, serum alanine aminotransferase (ALT), and body weight. Meta-analysis used random-effects models. We identified 12 RCTs (n=1,847). Pioglitazone significantly improved NAS (mean difference [MD] -1.2, 95% CI -1.8 to -0.6, p<0.001) and resolved steatohepatitis (RR 2.1, 95% CI 1.4-3.1). GLP-1 receptor agonists reduced liver fat (MD -4.5%, p<0.01) and ALT (MD -15 U/L, p<0.001). Novel agents, including resmetirom, showed promising effects on fibrosis (MD -0.3 stage, p=0.02). Adverse events were generally mild, with gastrointestinal symptoms most common. These findings support the use of MASLD pharmacotherapies in NAFLD, particularly pioglitazone and GLP-1 receptor agonists, though long-term safety and cost-effectiveness require further investigation.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_214
This study evaluates the innovation efficiency and overall performance of China's pharmaceutical manufacturing listed companies using a three-stage Data Envelopment Analysis (DEA) model and Tobit regression. Data from 2015 to 2019 were analyzed, encompassing 120 listed companies. The first-stage DEA revealed that the average innovation efficiency was 0.72, indicating significant room for improvement. After adjusting for environmental factors and statistical noise in the second stage, the third-stage DEA showed that the average efficiency increased to 0.85, suggesting that environmental variables such as government subsidies, market competition, and firm size significantly influenced efficiency. Specifically, government subsidies had a positive impact, while market competition had a negative effect. The Tobit regression further identified that R&D intensity, firm size, and ownership structure were significant determinants of innovation efficiency. The results indicate that the pharmaceutical industry in China has not yet achieved optimal innovation efficiency, and there is considerable heterogeneity among firms. The study recommends that policymakers should tailor support mechanisms to firm-specific characteristics, and managers should focus on enhancing R&D productivity and commercializing innovations. The findings provide empirical evidence for improving innovation efficiency in the pharmaceutical sector, contributing to the broader goal of industrial upgrading and sustainable development.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_212
Background: Trifluridine/tipiracil (TAS-102) plus bevacizumab (BEV) has shown promising activity in refractory metastatic colorectal cancer (mCRC). However, real-world data from Chinese populations are limited. Methods: This multicenter retrospective cohort study included 112 patients with mCRC who received TAS-102 plus BEV (n=56) or TAS-102 monotherapy (n=56) between January 2018 and December 2022. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: Median PFS was significantly longer in the combination group (5.6 months vs. 3.2 months; hazard ratio [HR] 0.58; 95% CI 0.38-0.89; p=0.012). Median OS was also improved (12.3 months vs. 8.9 months; HR 0.64; 95% CI 0.42-0.98; p=0.041). ORR was 12.5% in the combination group versus 5.4% in the monotherapy group (p=0.18), while DCR was 67.9% versus 46.4% (p=0.021). Grade ≥3 adverse events occurred in 41.1% of combination patients versus 33.9% of monotherapy patients (p=0.43); the most common were neutropenia (23.2% vs. 17.9%) and fatigue (12.5% vs. 10.7%). No treatment-related deaths occurred. Conclusions: TAS-102 plus bevacizumab significantly improved PFS and OS compared with TAS-102 monotherapy in Chinese patients with refractory mCRC, with a manageable safety profile. These findings support the use of this combination in clinical practice.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_215
The proliferation of chronic diseases necessitates precise and adaptive drug delivery systems. Conventional open-loop infusion protocols lack real-time feedback, leading to suboptimal therapeutic outcomes and increased risk of adverse events. This study presents a closed-loop drug delivery management system (CDDS) leveraging Internet of Things (IoT) architecture to enable real-time monitoring, data-driven decision-making, and automated dosage adjustment. The system integrates a wireless sensor network for continuous physiological monitoring (e.g., heart rate, blood pressure, glucose levels), a central control unit employing a proportional-integral-derivative (PID) algorithm for dose calculation, and an actuation module for precise drug administration. In a simulated clinical environment, the CDDS achieved a steady-state error of less than 2% and a response time of under 3 seconds for setpoint changes. The system demonstrated robust performance across a range of drug delivery scenarios, maintaining physiological parameters within target ranges for 95% of the operational time. Furthermore, the closed-loop architecture reduced manual intervention requirements by 80% compared to conventional protocols. The IoT-enabled platform also facilitated secure data transmission and remote monitoring, with a packet loss rate of less than 0.1% over a 24-hour continuous operation. These results indicate that the proposed CDDS offers a viable, scalable solution for personalized drug delivery, potentially improving therapeutic efficacy and patient safety in clinical settings.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_213
This multicenter, randomized, controlled trial evaluated the efficacy and safety of adjuvant chemotherapy with S-1 in patients with stage II/III gastric cancer following curative resection. A total of 1,025 patients were randomized to receive either S-1 (80 mg/m²/day on days 1-28 every 5 weeks for 1 year) or observation. The primary endpoint was 3-year disease-free survival (DFS). Secondary endpoints included overall survival (OS), safety, and quality of life. At a median follow-up of 38.5 months, the 3-year DFS rate was significantly higher in the S-1 group (72.3%) compared to the observation group (61.7%) (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.55-0.84; p < 0.001). The 3-year OS rate was also improved (82.4% vs. 74.6%; HR 0.72; 95% CI 0.56-0.93; p = 0.012). Grade 3/4 adverse events occurred in 28.4% of S-1 patients, with neutropenia (12.3%), anorexia (8.7%), and diarrhea (5.2%) being most common. Treatment adherence was high, with 78.6% of patients completing the full 1-year course. Subgroup analyses demonstrated consistent benefit across tumor stages and histological types. These findings support S-1 as a standard adjuvant therapy for stage II/III gastric cancer in Asian populations, offering a well-tolerated oral alternative to intravenous regimens.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_211
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and neuronal loss. Current therapeutic strategies remain largely symptomatic, underscoring the urgent need for effective preventive interventions. This consensus, formulated by a multidisciplinary panel of Chinese experts, evaluates the potential of granulocyte colony-stimulating factor (G-CSF) and its receptor (G-CSFR) as a preventive target for AD. Preclinical studies have demonstrated that G-CSF promotes neurogenesis, modulates neuroinflammation, and enhances synaptic plasticity, thereby mitigating AD-related pathology. The consensus synthesizes evidence from animal models and preliminary clinical observations, highlighting the role of G-CSFR-mediated signaling in neuroprotection. Key recommendations include the consideration of G-CSF as an adjunctive preventive strategy in high-risk populations, with careful monitoring of hematological parameters. The panel emphasizes the need for large-scale, randomized controlled trials to establish definitive clinical efficacy and safety. This consensus provides a framework for future research and clinical practice, aiming to bridge the gap between bench and bedside in AD prevention.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_239
Poly(lactic acid) (PLA) composites reinforced with cellulose nanofibers (CNFs) were prepared via melt blending followed by injection molding. CNFs were surface-modified with a silane coupling agent to improve interfacial adhesion. The effects of CNF content (0–5 wt%) on mechanical properties, thermal stability, and dynamic mechanical behavior were systematically investigated. Tensile strength increased from 58.2 MPa (neat PLA) to 72.4 MPa at 3 wt% CNF, a 24.4% improvement, while Young's modulus rose from 2.1 GPa to 3.0 GPa (42.9% increase). Flexural strength and modulus also improved significantly. Thermal stability, assessed by TGA, showed that the temperature at 5% weight loss (T5%) increased from 315°C to 338°C at 3 wt% CNF, indicating enhanced thermal resistance. DMA revealed a notable increase in storage modulus and a shift in glass transition temperature (Tg) from 58°C to 63°C, suggesting restricted polymer chain mobility due to strong CNF-PLA interactions. SEM micrographs confirmed uniform dispersion of CNFs at low loadings, with agglomeration observed at 5 wt%. The optimal CNF content was determined to be 3 wt%, providing a balance between mechanical reinforcement and processability. These findings demonstrate that surface-modified CNFs are effective bio-based reinforcing agents for PLA, offering a sustainable route to high-performance biodegradable composites for packaging and automotive applications.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_238
The therapeutic landscape of HER2-positive breast cancer remains constrained by the emergence of resistance to trastuzumab and the limited blood-brain barrier penetration of antibody-drug conjugates. This study introduces an engineered exosome platform (Exo-HER2) that co-delivers a HER2-targeting peptide and a microRNA-21 inhibitor, achieving dual suppression of oncogenic signaling and restoration of tumor suppressor networks. In vitro assays demonstrated a 72.4% reduction in HER2 phosphorylation (p < 0.001) and a 3.2-fold increase in apoptosis in SK-BR-3 cells compared to trastuzumab alone. In vivo, using an orthotopic xenograft model, systemic administration of Exo-HER2 resulted in a 68.5% tumor volume reduction (p < 0.01) and a 45.6% decrease in Ki-67 proliferation index. Notably, the exosome platform exhibited 8.7-fold higher blood-brain barrier penetration than free trastuzumab, as quantified by fluorescence imaging. Proteomic and transcriptomic analyses of tumor microenvironments revealed a 2.4-fold increase in CD8+ T cell infiltration and a 1.8-fold reduction in M2 macrophage polarization, indicating robust immunogenic modulation. Pharmacokinetic profiling showed a circulation half-life of 12.6 hours and a 5.2-fold higher tumor accumulation than the free drug. These findings establish Exo-HER2 as a versatile and potent therapeutic strategy, addressing key limitations of current HER2-targeted therapies and offering a promising avenue for clinical translation.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_234
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with complex molecular heterogeneity limiting therapeutic efficacy. Nuclear receptors (NRs) are transcription factors that regulate key metabolic and proliferative pathways, yet their role in HCC progression is not fully elucidated. Here, we performed a comprehensive multi-omics analysis integrating transcriptomic, proteomic, and phosphoproteomic data from 120 HCC tumor and adjacent non-tumor tissues. We identified 28 NRs significantly dysregulated in tumors, with 12 showing >2-fold change (p < 0.01). Notably, constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2) were upregulated in 85% of tumors, correlating with poor overall survival (hazard ratio = 2.3, p = 0.003). Functional studies using CRISPR-Cas9 knockout in HCC cell lines demonstrated that CAR knockout reduced cell proliferation by 45% and migration by 60% (p < 0.001). Mechanistically, CAR directly bound to the promoter of the multidrug resistance gene ABCB1, increasing its expression by 3.5-fold. Furthermore, we developed a NR-based prognostic signature comprising 5 NRs that stratified patients into high- and low-risk groups with distinct 5-year survival rates (32% vs. 78%, p < 0.0001). Our findings reveal a critical role for NR signaling in HCC aggressiveness and drug resistance, and provide a novel prognostic tool. Targeting NRs, particularly CAR, may represent a promising therapeutic strategy for HCC.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_236
This randomized controlled trial evaluated the efficacy and safety of combined antihypertensive therapy in patients with coronary heart disease (CHD) and hypertension. A total of 240 patients were randomized to receive either combination therapy (amlodipine 5 mg plus perindopril 4 mg) or monotherapy (amlodipine 5 mg) for 24 weeks. The primary endpoint was the change in systolic blood pressure (SBP) from baseline to week 24. Secondary endpoints included diastolic blood pressure (DBP), heart rate, adverse events, and laboratory parameters. Results showed that combination therapy reduced SBP by 23.5 mmHg (from 158.2±12.3 to 134.7±8.9 mmHg) compared to 18.2 mmHg (from 157.8±11.9 to 139.6±9.2 mmHg) with monotherapy (p<0.01). DBP reductions were 12.4 mmHg and 9.8 mmHg, respectively (p<0.05). The combination group achieved target BP (<140/90 mmHg) in 82.5% of patients versus 65.0% in the monotherapy group (p<0.01). Adverse events were comparable between groups (12.5% vs 10.8%, p>0.05), with no serious adverse events. Laboratory tests showed no significant changes in renal function, electrolytes, or liver enzymes. In conclusion, combination therapy with amlodipine and perindopril provides superior blood pressure control without increasing adverse events in CHD patients, supporting its use as an effective strategy for hypertension management in this high-risk population.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_237
This study investigates the spatiotemporal dynamics of nitrogen dioxide (NO2) and ozone (O3) interactions across multiple urban monitoring sites. Continuous measurements were conducted over a 12-month period, capturing hourly concentrations of NO2, O3, and related meteorological parameters. Results reveal a pronounced inverse correlation between NO2 and O3, with correlation coefficients ranging from -0.72 to -0.85 across sites. The ozone formation regime was identified as VOC-limited in urban core areas, transitioning to NOx-limited in suburban zones. Diurnal profiles show that O3 peaks occur 3-4 hours after NO2 minima, indicating photochemical production. Statistical analysis using a generalized additive model explained 78% of O3 variability, with NO2 contributing 34% and temperature 22%. The study further delineates the impact of weekend effects, where reduced NO2 emissions lead to a 12% increase in O3 concentrations due to VOC-limited chemistry. These findings underscore the need for coordinated control of NOx and VOC emissions to mitigate O3 pollution. The data provide a robust basis for refining air quality models and informing policy decisions aimed at reducing secondary pollutant formation in urban environments.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_254
This prospective phase II trial evaluated the efficacy and safety of neoadjuvant chemotherapy combined with anti-PD-1 immunotherapy in patients with resectable non-small cell lung cancer (NSCLC). A total of 30 patients with stage IIIA NSCLC received two cycles of platinum-based chemotherapy plus pembrolizumab (200 mg) prior to surgery. The primary endpoint was major pathological response (MPR), defined as ≤10% viable tumor cells in the resected specimen. Secondary endpoints included pathological complete response (pCR), overall response rate (ORR), and safety. Results demonstrated an MPR rate of 60% (18/30) and a pCR rate of 33.3% (10/30). The ORR was 70% (21/30) by RECIST 1.1. Grade 3 or higher treatment-related adverse events occurred in 20% of patients, with no treatment-related deaths. The combination regimen showed promising antitumor activity with manageable toxicity, supporting further investigation in larger randomized trials.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_229
Traditional Chinese Medicine (TCM) has been widely used for centuries, yet its complex chemical composition and mechanisms of action remain inadequately characterized. This systematic review synthesizes current evidence on the chemical constituents, pharmacological activities, and quality control methods of TCM, with a focus on the 'yt|' compound. A comprehensive literature search identified 28 relevant studies. Key findings indicate that the primary active components include flavonoids, alkaloids, and saponins, which exhibit anti-inflammatory, antioxidant, and anticancer properties. Notably, the compound demonstrated significant efficacy in reducing tumor growth by 45% in vitro and 30% in vivo, with an IC50 of 12.5 μM. Quality control analyses revealed that high-performance liquid chromatography (HPLC) fingerprinting can reliably distinguish authentic samples from adulterants, with a similarity index above 0.95. Furthermore, the review highlights the importance of standardization in TCM, as variations in cultivation and processing significantly affect bioactivity. The integration of metabolomics and network pharmacology has advanced our understanding of the multi-target mechanisms of TCM. However, challenges remain in establishing robust quality standards and clinical evidence. This review underscores the potential of TCM as a source of novel therapeutic agents and calls for rigorous scientific validation to support its global acceptance.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_232
Drug-induced liver injury (DILI) remains a leading cause of drug attrition and post-marketing withdrawals. Traditional preclinical models often fail to predict human hepatotoxicity accurately. Here, we developed a novel hepatic spheroid model using primary human hepatocytes and evaluated its transcriptomic and functional responses to a panel of known hepatotoxicants. We integrated high-content imaging, biochemical assays, and RNA-seq data to train machine learning classifiers for DILI prediction. Our model achieved an area under the receiver operating characteristic curve (AUC) of 0.92 (95% CI: 0.88-0.96) on a validation set of 150 compounds, outperforming conventional 2D cultures (AUC=0.78) and animal models (AUC=0.71). Key predictive biomarkers included genes involved in oxidative stress, mitochondrial dysfunction, and bile acid transport. The spheroid model exhibited enhanced sensitivity for detecting cholestatic and steatotic hepatotoxicants, with a positive predictive value of 89% for compounds causing severe DILI. Our findings demonstrate that combining physiologically relevant 3D liver models with machine learning offers a robust platform for early DILI risk assessment, potentially reducing late-stage drug failures and improving patient safety.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_231
Non-small cell lung cancer (NSCLC) exhibits heterogeneous clinical trajectories, necessitating robust predictive models for personalized therapy. We integrated transcriptomic, genomic, and clinical data from 1,024 NSCLC patients (cohort A: 612, cohort B: 412) to develop a machine learning framework for overall survival (OS) and progression-free survival (PFS) prediction. Using a random survival forest algorithm with 500 trees and 10-fold cross-validation, we achieved a concordance index (C-index) of 0.78 (95% CI: 0.74-0.82) for OS and 0.75 (95% CI: 0.71-0.79) for PFS in the validation cohort. Key predictive biomarkers included tumor mutation burden (TMB), PD-L1 expression, and specific immune cell infiltration signatures. The model stratified patients into high- and low-risk groups with median OS of 18.2 vs. 42.6 months (p < 0.001). Furthermore, we identified a 15-gene immune-related signature that independently predicted response to immune checkpoint inhibitors (AUC = 0.82). Our findings demonstrate that integrating multi-omics data with clinical parameters significantly improves prognostic accuracy over clinical variables alone (C-index improvement: +0.12). This framework offers a clinically actionable tool for treatment stratification and trial design.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_253
This study presents a novel electrochemical sensor employing AL.CY.cL as the sensing material for the detection of neurotransmitters. The sensor exhibits high sensitivity and selectivity, with a detection limit of 0.5 μM for dopamine and 0.8 μM for serotonin. The linear range spans from 1 μM to 100 μM for both analytes, with correlation coefficients exceeding 0.99. The sensor demonstrates excellent reproducibility (RSD < 5%) and stability over 30 days. Interference studies show negligible response to ascorbic acid and uric acid at physiological concentrations. The sensor was successfully applied to real sample analysis in artificial cerebrospinal fluid, achieving recovery rates between 95% and 105%. The AL.CY.cL-based sensor offers a promising platform for rapid, cost-effective neurotransmitter monitoring, potentially enabling point-of-care diagnostics and real-time neurochemical monitoring.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_246
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with high recurrence and drug resistance rates. This study integrates multi-omics data (genomics, transcriptomics, proteomics) and machine learning algorithms to identify novel therapeutic targets and prognostic biomarkers. We analyzed 450 HCC samples from public databases and our cohort, applying LASSO and random forest feature selection to identify a 12-gene signature associated with overall survival (p < 0.001). Functional experiments demonstrated that knockdown of the top candidate gene, TPX2, reduced cell proliferation by 45% and migration by 60% in vitro. Drug resistance analysis revealed that TPX2 overexpression confers resistance to sorafenib (IC50 increased from 2.5 μM to 8.2 μM). Furthermore, we developed a nomogram integrating clinical factors and the gene signature, achieving a C-index of 0.82 (95% CI: 0.78-0.86) for predicting 5-year survival. Our findings provide a robust framework for personalized therapy and risk stratification in HCC.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_249
Benign prostatic hyperplasia (BPH) is a common urological condition in aging men, often managed with combination therapy. This randomized controlled trial evaluated the efficacy and safety of a combined traditional Chinese medicine (TCM) and Western medicine regimen versus Western medicine alone in patients with moderate-to-severe BPH. A total of 120 patients were randomized to receive either combination therapy (TCM formula plus tamsulosin) or tamsulosin monotherapy for 12 weeks. The primary outcome was the change in International Prostate Symptom Score (IPSS). Secondary outcomes included peak urinary flow rate (Qmax), post-void residual volume (PVR), and prostate volume. Results showed that the combination group had a significantly greater reduction in IPSS (mean change -8.2 vs -5.4, p<0.01) and improvement in Qmax (+4.5 mL/s vs +2.8 mL/s, p<0.05) compared to the control group. PVR decreased by 32 mL in the combination group versus 18 mL in the control group (p<0.05). Prostate volume reduction was modest but not statistically significant. Adverse events were mild and comparable between groups. The combination of TCM and tamsulosin demonstrated superior symptomatic relief and urinary flow improvement without additional safety concerns, suggesting a beneficial role for integrative therapy in BPH management.