Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03654-y
Background Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) plays a pivotal role in inducing metabolic inflammation in diabetes. Additionally, the NOD1 ligand disrupts the equilibrium of bone marrow-derived hematopoietic stem/progenitor cells, a process that has immense significance in the development of diabetic retinopathy (DR). We hypothesized that NOD1 depletion impedes the advancement of DR by resolving bone marrow dysfunction. Methods We generated NOD1−/−-Akita double-mutant mice and chimeric mice with hematopoietic-specific NOD1 depletion to study the role of NOD1 in the bone marrow–retina axis. Results Elevated circulating NOD1 activators were observed in Akita mice after 6 months of diabetes. NOD1 depletion partially restored diabetes-induced structural changes and retinal electrical responses in NOD1−/−-Akita mice. Loss of NOD1 significantly ameliorated the progression of diabetic retinal vascular degeneration, as determined by acellular capillary quantification. The preventive effect of NOD1 depletion on DR is linked to bone marrow phenotype alterations, including a restored HSC pool and a shift in hematopoiesis toward myelopoiesis. We also generated chimeric mice with hematopoietic-specific NOD1 ablation, and the results further indicated that NOD1 had a protective effect against DR. Mechanistically, loss of hematopoietic NOD1 resulted in reduced bone marrow-derived macrophage infiltration and decreased CXCL1 and CXCL2 secretion within the retina, subsequently leading to diminished neutrophil chemoattraction and NETosis. Conclusions The results of our study unveil, for the first time, the critical role of NOD1 as a trigger for a hematopoietic imbalance toward myelopoiesis and local retinal inflammation, culminating in DR progression. Targeting NOD1 in bone marrow may be a potential strategy for the prevention and treatment of DR.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.15.20261504
This study establishes an integrated strategy for rapid screening of pancreatic lipase (PPL) inhibitors from Rheum palmatum and elucidates their anti-obesity mechanisms. Fe3O4@SiO2@PPL magnetic nanoparticles were synthesized via chemical co-precipitation, Stöber method, and cross-linking, and characterized by FTIR, SEM, and XRD. Ligand fishing from a 30% ethanol extract specifically captured four compounds: chrysophanol-8-O-β-D-glucopyranoside, aloe-emodin, rhein, and chrysophanol. In vitro enzyme assays confirmed that chrysophanol and aloe-emodin exhibited potent PPL inhibition with IC50 values of 67.03 and 85.86 µmol/L, respectively. Molecular docking revealed that these active components form hydrogen bonds and hydrophobic interactions with key amino acid residues of PPL, consistent with experimental inhibition. Network pharmacology identified 150 overlapping targets between the active compounds and obesity, with five core targets: EGFR, AKT1, SRC, HSP90AA1, and BCL2. Pathway enrichment analysis highlighted the HIF-1 signaling pathway and lipid and atherosclerosis pathway as principal mechanisms. The developed 'material screening–computational validation–network prediction' platform offers a robust tool for high-throughput discovery of natural PPL inhibitors and provides methodological reference for multi-target mechanistic studies of traditional Chinese medicine.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261614
Aging-related sarcopenia remains a clinical challenge due to limited effective interventions. This study systematically evaluated the therapeutic potential of the iridoid fraction from Morinda officinalis and elucidated its mechanism via the PI3K/Akt/mTOR pathway. Using monotropein and deacetylasperulosidic acid as markers, extraction was optimized with 60% ethanol under heated reflux, yielding the highest iridoid content. Purification employed H103 macroporous resin with water as eluent, achieving maximal recovery. In vitro, the fraction significantly ameliorated D-galactose-induced C2C12 myotube atrophy (P < 0.001) and promoted myotube differentiation (P < 0.05, 0.01, 0.001), as evidenced by MYHC expression. In vivo, D-galactose-accelerated aging mice treated with the fraction exhibited increased limb grip strength and hindlimb muscle mass-to-body weight ratio (P < 0.05, 0.01, 0.001), along with expanded cross-sectional area of tibialis anterior and gastrocnemius muscles (P < 0.01, 0.001). Transcriptomic and network pharmacology analyses implicated the PI3K/Akt pathway. Western blotting and qRT-PCR confirmed upregulation of key proteins and genes (PIK3CA, AKT1, mTOR) in the pathway (P < 0.05, 0.01, 0.001), while the PI3K inhibitor LY294002 reversed these effects (P < 0.05). These findings demonstrate that the iridoid fraction from M. officinalis mitigates aging-related sarcopenia through PI3K/Akt/mTOR signaling, providing a promising candidate for clinical translation.
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_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 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•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: cast_zgxyzz_1236731781232251260
Background: Iron deficiency anemia (IDA) is a global health concern, and intravenous iron preparations are increasingly used. Ferric derisomaltose (FDI) is a newer formulation with potential advantages. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of FDI compared with other iron therapies or placebo in treating IDA. Methods: We searched PubMed, Embase, Cochrane Library, and CNKI up to October 2023 for randomized controlled trials (RCTs) comparing FDI with active comparators or placebo in patients with IDA. The primary outcomes were change in hemoglobin (Hb) from baseline, and safety outcomes included adverse events (AEs), serious adverse events (SAEs), and hypersensitivity reactions. Data were pooled using random-effects models. Results: A total of 15 RCTs involving 3,452 patients were included. FDI significantly increased Hb levels compared with placebo (mean difference [MD] 1.2 g/dL, 95% CI 0.8-1.6) and was non-inferior to other intravenous iron formulations (MD 0.1 g/dL, 95% CI -0.2 to 0.4). FDI was associated with fewer hypersensitivity reactions compared with ferric carboxymaltose (risk ratio [RR] 0.3, 95% CI 0.1-0.9). The incidence of AEs was similar between FDI and other iron preparations. Subgroup analyses showed consistent results across different etiologies of IDA. Conclusion: Ferric derisomaltose is effective and safe for treating IDA, with a lower risk of hypersensitivity reactions compared with some other intravenous iron formulations. These findings support its use in clinical practice.
Chinese Journal of New Drugs•2025•DOI: cast_zgxyzz_1236731784289907521
A comprehensive analytical method was developed and validated for the simultaneous determination of multiple bioactive components in traditional Chinese medicine (TCM) formulations. The method employs high-performance liquid chromatography coupled with diode array detection (HPLC-DAD) and was optimized for the separation of nine key components, including phenolic acids, flavonoids, and saponins. Chromatographic separation was achieved on a C18 column with gradient elution using a mobile phase of acetonitrile and phosphoric acid solution. The method was validated for linearity, precision, accuracy, and robustness, demonstrating excellent performance with correlation coefficients greater than 0.999. The limits of detection and quantification ranged from 0.02 to 0.15 μg/mL and 0.05 to 0.50 μg/mL, respectively. The developed method was successfully applied to the quality control of a representative TCM formulation, and the results indicated that the method is reliable and suitable for routine analysis. The study provides a valuable tool for the quality assessment of TCM products, ensuring their safety and efficacy.
Chinese Journal of New Drugs•2025•DOI: cast_zgxyzz_1236731781714596256
Background: The inflammatory burden index (IBI), derived from C-reactive protein (CRP) and albumin, has emerged as a prognostic biomarker in various cancers. However, its role in non-small cell lung cancer (NSCLC) remains unclear. Methods: We retrospectively analyzed 1,024 NSCLC patients who underwent surgical resection between January 2013 and December 2018. The IBI was calculated as CRP × albumin. Optimal cutoff values were determined by X-tile software. Patients were divided into high and low IBI groups. Univariate and multivariate Cox regression analyses identified independent prognostic factors. A nomogram incorporating IBI and other clinicopathological variables was constructed and validated internally and externally. Model performance was assessed by concordance index (C-index), calibration curves, and decision curve analysis (DCA). Results: The optimal cutoff for IBI was 0.36. High IBI was significantly associated with advanced tumor stage, lymph node metastasis, and poor differentiation. Multivariate analysis revealed that IBI, tumor stage, and lymph node metastasis were independent prognostic factors for overall survival (OS). The nomogram achieved a C-index of 0.72 (95% CI: 0.68-0.76) in the training cohort and 0.70 (95% CI: 0.65-0.75) in the validation cohort. Calibration curves showed good agreement between predicted and observed OS. DCA demonstrated that the nomogram provided a net clinical benefit. Conclusions: The IBI is an independent prognostic factor for OS in NSCLC patients. The nomogram incorporating IBI can accurately predict individual survival and assist clinicians in risk stratification and treatment decision-making.
Chinese Journal of New Drugs•2025•DOI: cast_zgxyzz_1236731785313317742
Background: Heart failure with recovered ejection fraction (HFrecEF) is a distinct phenotype with unclear clinical characteristics and prognosis. Methods: We prospectively enrolled 1,234 patients with heart failure and reduced ejection fraction (HFrEF) from January 2015 to December 2018. After optimal medical therapy, 312 patients (25.3%) achieved recovery of left ventricular ejection fraction (LVEF) to ≥50% and were classified as HFrecEF. Clinical characteristics, medication use, and outcomes were compared with those who remained HFrEF. The primary outcome was a composite of all-cause death and heart failure hospitalization. Results: Compared with HFrEF patients, HFrecEF patients were younger, more likely to be female, had a higher prevalence of hypertension and atrial fibrillation, and had a shorter duration of heart failure. They had lower baseline levels of NT-proBNP and smaller left ventricular dimensions. Over a median follow-up of 3.2 years, HFrecEF patients had a significantly lower risk of the primary outcome (adjusted HR 0.45, 95% CI 0.32-0.63, p<0.001). However, 23.4% of HFrecEF patients experienced deterioration of LVEF during follow-up, and these patients had a worse prognosis compared with those who maintained recovery. Independent predictors of LVEF deterioration included ischemic etiology, diabetes, and non-adherence to guideline-directed medical therapy. Conclusions: HFrecEF is associated with a better prognosis than HFrEF, but a substantial proportion of patients may experience LVEF deterioration. Continued optimization of medical therapy and close monitoring are essential for this population.
Chinese Journal of New Drugs•2025•DOI: cast_zgxyzz_1236731781714596256
A rapid, sensitive, and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of isavuconazole in human plasma. Sample preparation involved a simple protein precipitation with acetonitrile. Chromatographic separation was achieved on a C18 column using a gradient elution with a mobile phase consisting of 0.1% formic acid in water and acetonitrile. The method was validated over a linear range of 5.00-5000 ng/mL with a lower limit of quantification of 5.00 ng/mL. The intra- and inter-run precision (relative standard deviation, RSD) were less than 8.5% and 9.2%, respectively, and accuracy (relative error, RE) ranged from -3.2% to 4.5%. The method was successfully applied to a pharmacokinetic study in healthy Chinese volunteers after oral administration of isavuconazole. The key pharmacokinetic parameters, including maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and area under the plasma concentration-time curve (AUC), were determined. The results demonstrated that the method is suitable for therapeutic drug monitoring and pharmacokinetic studies of isavuconazole.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_236
Background: High-intensity focused ultrasound (HIFU) is a non-invasive therapeutic modality for uterine fibroids. However, its efficacy and safety compared with conventional surgery remain debated. Methods: In this multicenter, randomized, controlled trial, we randomly assigned 200 women with symptomatic uterine fibroids to undergo HIFU ablation (n=100) or myomectomy (n=100). The primary endpoint was the reduction in fibroid volume at 6 months. Secondary endpoints included symptom severity score, quality of life, and adverse events. Results: At 6 months, the mean reduction in fibroid volume was 45.2% in the HIFU group versus 58.7% in the surgery group (P<0.001). Symptom severity scores improved significantly in both groups, with no significant difference between groups (P=0.32). Quality of life scores were comparable. Adverse events were fewer in the HIFU group (12% vs. 28%, P=0.004). Conclusion: HIFU is a safe and effective alternative to surgery for symptomatic uterine fibroids, offering comparable symptomatic relief with fewer adverse events, despite a smaller reduction in fibroid volume.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_158
Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder with increasing global prevalence. Traditional Chinese Medicine (TCM) has been used for centuries to manage diabetes, but its efficacy and safety remain controversial. This study aimed to evaluate the efficacy and safety of a TCM formula (GEL) in patients with T2DM. Methods: A randomized, double-blind, placebo-controlled trial was conducted. A total of 240 patients with T2DM were randomly assigned to receive either GEL or placebo for 12 weeks. The primary outcome was the change in HbA1c levels from baseline. Secondary outcomes included fasting plasma glucose (FPG), postprandial plasma glucose (PPG), lipid profiles, and adverse events. Results: After 12 weeks, the GEL group showed a significant reduction in HbA1c compared to placebo (mean difference -0.8%, 95% CI -1.2 to -0.4, p<0.001). FPG and PPG also decreased significantly in the GEL group. No serious adverse events were reported. Conclusion: GEL was effective and safe in improving glycemic control in patients with T2DM. Further studies are warranted to confirm these findings and explore the underlying mechanisms.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_190
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with late diagnosis contributing to poor prognosis. This study integrates transcriptomic and proteomic analyses to identify novel biomarkers for early detection and prognostic assessment of HCC. Using RNA sequencing and mass spectrometry on tumor and adjacent non-tumor tissues from 120 HCC patients, we identified 45 differentially expressed genes and 23 proteins consistently altered in HCC. Among these, a panel of five biomarkers (including AFP, GPC3, and three novel candidates) demonstrated high sensitivity (92%) and specificity (88%) for early-stage HCC detection. Furthermore, a prognostic signature based on these biomarkers stratified patients into high- and low-risk groups with significantly different overall survival (p < 0.001). Our findings provide a robust multi-omics framework for HCC management, potentially improving clinical outcomes through earlier intervention and personalized treatment strategies.