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Peking Union Medical College

Verified scientific contributions, CAS laboratory outputs, clinical trial papers, and engineering breakthroughs produced by researchers and faculty affiliated with Peking Union Medical College.

Stem Cell Research & Therapy•2026

Research based on serine metabolism indicates mesenchymal stem cells alleviate psoriasis by regulating the PSPH-PINK1-Parkin-NLRP3 pathway in HaCaT

Authors: Qing Lin, Yunfei Ji, Bin Yang, Rongjia Zhu, Ping Song, Robert Chunhua Zhao

Background: Psoriasis is a refractory immune-related disease. In recent years, it has been discovered that mesenchymal stem cells (MSCs) can be used as a new therapeutic approach for psoriasis, but their potential therapeutic mechanism remains unclear. This study aims to explore the role of MSCs in the treatment of psoriasis. Methods: We employed a mouse psoriasis model induced by imiquimod (IMQ) in vivo and a co-culture system of MSCs and HaCaT keratinocytes (KCs) cell line in vitro. These approaches allowed us to investigate the effect of MSCs on the levels of inflammatory factors and the activation of inflammasomes in both contexts. Mouse-targeted amino acid sequencing, transmission electron microscopy for in vitro observation, immunofluorescence for both in vivo and in vitro analyses, and siRNA transfection in vitro were employed in this study. Results: Our results showed that MSCs significantly improved the skin lesion of mice with psoriasis, and reduced the levels of inflammatory factors and chemokines including IL-1β, IL-6, IL-8, TNF-α, MCP-1, CCL7, CCL20 and CCL27 in the mouse skin lesion areas and M5-induced psoriatic KCs models in vitro. Likewise, MSCs repaired the skin barrier by enhancing claudin-1 expression in vivo. In addition, MSCs increased KRT1 and decreased KRT6 levels in vivo and in vitro. Amino acid metabolism analysis showed that MSCs could improve the serine metabolism level in the mouse skins and upregulated the key enzyme phosphoserine phosphatase (PSPH) in serine metabolism. In vitro experiments demonstrated that knockdown of PSPH could reverse the therapeutic effects of MSCs on psoriasis. Furthermore, studies in vitro and in vivo revealed that MSCs can activate the PINK1-Parkin pathway. It was specifically manifested by elevated levels of PINK1, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, coupled with a reduction in P62 protein. Subsequently, the activation of PINK1-Parkin led to decreased expressions of IL-1β, IL-6, IL-8, TNF-α, CCL7, CCL20, CCL27, and MCP-1. In vitro and in vivo experiments indicated that MSCs can reduce the levels of these inflammatory factors by inhibiting the activation of NLRP3 inflammasomes. Meanwhile, PSPH knockdown in vitro can reverse the activating effects of MSCs on the PINK1-Parkin, as shown by decreased levels of PINK, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, concurrently with an elevation in P62. Conclusions: The results of this study indicated that MSCs can alleviate IMQ-induced psoriasiform dermatitis in mice by upregulating serine metabolism. The key serine metabolism enzyme PSPH may enhance PINK1/Parkin-mediated mitochondrial autophagy in psoriatic HaCaT and inhibit NLRP3 inflammasome activation in HaCaT cells, thereby alleviating skin inflammatory responses and suppressing skin proliferation in psoriatic mice.

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Chinese Journal of New Drugs•2026

Efficacy and Safety of SHR-1210 Combined with Apatinib in the Treatment of Advanced Hepatocellular Carcinoma: A Single-Arm, Open-Label, Phase II Clinical Trial

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing, LIU Yang, ZHAO Lei, SUN Hong, ZHOU Qiang, WU Tao, XU Lin

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.

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Chinese Journal of New Drugs•2026

Artificial Intelligence in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis of Diagnostic and Prognostic Accuracy

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing, LIU Yang, ZHAO Lei, SUN Hong, ZHOU Qiang, WU Na, XU Dan

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.

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Acta Biochimica et Biophysica Sinica•2026

Distinct miR319a Identified from Persicaria chinensis Mediates Cross-Kingdom Suppression of Cervical Cancer by Targeting ITGA3

Authors: YAN Yueyue, BAI Dan, LI Lei, XU Leimei, YANG Hua, WANG Yuhui, FENG Han, ZHU Lan

Persicaria chinensis, a well-known traditional Chinese medicinal herb that is both edible and medicinal, has been widely acknowledged for its therapeutic effects, such as anti-inflammatory, antioxidant, and antitumor activities. However, the role of miRNAs from this plant in the cross-kingdom regulation of human diseases has not been investigated. In this study, we analyze the miRNA expression profile of P. chinensis using high-throughput sequencing and identify a total of 673 miRNAs, including 422 novel miRNAs that are unique to this plant and 251 conserved miRNAs. Among the conserved miRNAs, pch-miR319a is found to be the most abundant. Moreover, food-oriented pch-miR319a accumulates in the uterus and tumors and exhibits a rich repertoire of target genes within cancer-related pathways, demonstrating significant cross-kingdom regulatory potential. Utilizing the dual-luciferase reporter gene assay, we demonstrate that pch-miR319a from P. chinensis targets the Itga3 gene, which is associated with cervical cancer progression. Overexpression of pch-miR319a significantly decreases the viability, migration, and induces apoptosis of HeLa cervical cancer cells in vitro. Moreover, in a syngeneic mouse tumor model of cervical cancer, treatment with pch-miR319a effectively inhibits tumor growth and downregulates the expressions of ITGA3 and the proliferation marker Ki-67. Our study highlights the potential of pch-miR319a from P. chinensis as a novel therapeutic agent for cervical cancer by targeting ITGA3 and provides new insights into the cross-kingdom regulatory mechanisms of plant miRNAs in human diseases.

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Stem Cell Research & Therapy•2026

iPSC-derived exosomes promote diabetic wound healing by attenuating inflammatory responses

Authors: Li Long, Ju Qiao, Liang Wang, Yue Wang, Yi Xu, Hui Chen, Hongzhong Jin, Wei He, Xiaohong Han, Jianmin Zhang

Background: Owing to impaired glucose metabolism, the high-glucose microenvironment in diabetic patients disrupts a series of biological reactions that hinder the wound healing process, resulting in a significant cost to the health care system and an urgent need for new and advanced therapies. Methods: In this study, induced pluripotent stem cell-derived exosomes (iPSC-Exos) were isolated from iPSC culture supernatant via centrifugation and ultrafiltration. We evaluated the therapeutic effects of iPSC-Exos on diabetic wound healing through two clinically relevant animal models (spontaneous genetic diabetic mouse model and streptozotocin (STZ)-induced diabetic mouse model). iPSC-Exos were topically administered to full-thickness cutaneous wounds in diabetic mice. The therapeutic effects were systematically assessed by measuring wound closure rates, conducting comprehensive histopathological evaluations, and performing quantitative analysis of inflammatory mediators via ELISA. Results: We demonstrated that iPSC-Exos can significantly accelerate diabetic wound healing through two clinically relevant animal models (spontaneous genetic diabetic mouse model and STZ-induced diabetic mouse model) for the first time. The multifaceted therapeutic mechanisms include: (i) Direct activation of tissue regeneration (promotion of re-epithelialization, tissue remodeling and scar attenuation); (ii) Modulation of the inflammatory microenvironment (promoting macrophage polarization toward anti-inflammatory M2 phenotype/suppressing inflammation). Conclusions: This dual-animal model approach, which closely recapitulates key pathophysiological features of human diabetic wounds, offers superior clinical translatability compared to single-animal model studies. Our findings iPSC-derived exosomes promote diabetic wound healing by attenuating inflammatory responses.

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Stem Cell Research & Therapy•2026

Stem cell-based therapies for alopecia areata: a narrative review

Authors: Aiping Fan, Mingjuan Liu, Jun Li

Alopecia Areata (AA) is a chronic inflammatory disorder characterized by non-scarring, patchy hair loss that may progress to the entire scalp (alopecia totalis) or body (alopecia universalis), significantly impairing patients’ quality of life and psychological health. Although the exact pathogenesis of AA remains unclear, current evidence suggests that the breakdown of hair follicle immune privilege (IP) and subsequent autoimmune-mediated follicular attack play a pivotal role. Conventional therapeutic modalities, including corticosteroid and Janus kinase (JAK) inhibitors, are often limited by suboptimal efficacy in severe cases and high relapse rates following treatment cessation. In recent years, stem cell-based therapy has emerged as a novel treatment for AA, showing therapeutic potential through multiple mechanisms. Preliminary clinical trials have indicated significant efficacy in promoting hair regrowth among AA patients. However, comprehensive evaluation of long-term safety and therapeutic efficacy remains imperative. This review article aims to give a comprehensive overview of the recent advances in stem cell-based therapies for AA and explore their underlying mechanisms and clinical application prospects, hoping to provide a framework and reference for future research and clinical practice.

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Stem Cell Research & Therapy•2026

Research based on serine metabolism indicates mesenchymal stem cells alleviate psoriasis by regulating the PSPH-PINK1-Parkin-NLRP3 pathway in HaCaT

Authors: Qing Lin, Yunfei Ji, Bin Yang, Rongjia Zhu, Ping Song, Robert chunhua Zhao

Background Psoriasis is a refractory immune-related disease. In recent years, it has been discovered that mesenchymal stem cells (MSCs) can be used as a new therapeutic approach for psoriasis, but their potential therapeutic mechanism remains unclear. This study aims to explore the role of MSCs in the treatment of psoriasis. Methods We employed a mouse psoriasis model induced by imiquimod (IMQ) in vivo and a co-culture system of MSCs and HaCaT keratinocytes (KCs) cell line in vitro. These approaches allowed us to investigate the effect of MSCs on the levels of inflammatory factors and the activation of inflammasomes in both contexts. Mouse-targeted amino acid sequencing, transmission electron microscopy for in vitro observation, immunofluorescence for both in vivo and in vitro analyses, and siRNA transfection in vitro were employed in this study. Results Our results showed that MSCs significantly improved the skin lesion of mice with psoriasis, and reduced the levels of inflammatory factors and chemokines including IL-1β, IL-6, IL-8, TNF-α, MCP-1, CCL7, CCL20 and CCL27 in the mouse skin lesion areas and M5- induced psoriatic KCs models in vitro. Likewise, MSCs repaired the skin barrier by enhancing claudin-1 expression in vivo. In addition, MSCs increased KRT1 and decreased KRT6 levels in vivo and in vitro. Amino acid metabolism analysis showed that MSCs could improve the serine metabolism level in the mouse skins and upregulated the key enzyme phosphoserine phosphatase (PSPH) in serine metabolism. In vitro experiments demonstrated that knockdown of PSPH could reverse the therapeutic effects of MSCs on psoriasis. Furthermore, studies in vitro and in vivo revealed that MSCs can activate the PINK1-Parkin pathway. It was specifically manifested by elevated levels of PINK1, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, coupled with a reduction in P62 protein. Subsequently, the activation of PINK1-Parkin led to decreased expressions of IL-1β, IL-6, IL-8, TNF-α, CCL7, CCL20, CCL27, and MCP-1. In vitro and in vivo experiments indicated that MSCs can reduce the levels of IL-1β, IL-6, IL-8, TNF-α, CCL7, CCL20, CCL27, and MCP-1 by inhibiting the activation of NLRP3 inflammasomes. Meanwhile, PSPH knockdown in vitro can reverse the activating effects of MSCs on the PINK1-Parkin, as shown by decreased levels of PINK, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, concurrently with an elevation in P62. Conclusions The results of this study indicated that MSCs can alleviate IMQ-induced psoriasiform dermatitis in mice by upregulating serine metabolism. The key serine metabolism enzyme PSPH may enhance PINK1/Parkin-mediated mitochondrial autophagy in psoriatic HaCaT and inhibit NLRP3 inflammasome activation in HaCaT cells, thereby alleviating skin inflammatory responses and suppressing skin proliferation in psoriatic mice.

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Stem Cell Research & Therapy•2026

Spatiotemporal single-cell atlas of suture stem cell dynamics in craniosynostosis

Authors: Xinyan Chen, Chenzhi Lai, Tian He, Zong Chen, Xiaolei Jin

Background: Craniosynostosis is a congenital disorder characterized by premature suture fusion and aberrant skull morphogenesis. The cellular dynamics and regulatory mechanisms of suture mesenchymal stem cells (SuSCs) in this disease remain poorly defined. Methods: We integrated single-cell RNA sequencing and 2-μm-resolution Visium HD spatial transcriptomics to build a spatiotemporal atlas of coronal suture cells in Fgfr2C342Y/+ mice, a murine model recapitulating human Crouzon syndrome, alongside wild-type controls across three key developmental stages (E14.5, E18.5, and P3). To obtain near single-cell spatial resolution, we created SpatialCell, which combines morphology-based segmentation and machine-learning classification using a reference trained on our single-cell datasets. Results: The atlas reveals stage-specific remodeling of SuSC niches and a shift of SuSC spatial associations toward osteogenic mesenchyme in craniosynostosis. Along the SuSC-to-osteoblast trajectory, pre-osteoblasts were depleted earlier than upstream SuSCs, and SuSCs displayed premature acquisition of osteogenic programs near the suture midline. Temporal Gene Ontology patterns indicated early extracellular-matrix disruption, mid-gestation chondrogenic activation, and postnatal mineralization. Network analysis nominated Foxa3 as a candidate regulator in SuSC subsets; siRNA knockdown of Foxa3 reduced ex vivo mineralization in the craniosynostosis background. Spatial communication analyses implicated signals from suture meningeal fibroblasts and immune cells that converge on SuSC fate. Conclusions: Our results support a model where craniosynostosis may involve disrupted temporal coordination of developmental programs, not merely accelerated bone formation. The atlas and analytic framework pinpoint when and where SuSC fate diverges, propose Foxa3 as an intervention target, and provide a high-resolution resource for mechanistic and therapeutic exploration.

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Acta Biochimica et Biophysica Sinica•2026

Distinct miR319a identified from Persicaria chinensis mediates cross-kingdom suppression of cervical cancer by targeting ITGA3

Authors: Yueyue Yan, Dan Bai, Lei Li, Leimei Xu, Hua Yang, Yuhui Wang, Han Feng, Lan Zhu

Persicaria chinensis, a well-known traditional Chinese medicinal herb that is both edible and medicinal, has been widely acknowledged for its therapeutic effects, such as anti-inflammatory, antioxidant, and antitumor activities. However, the role of miRNAs from this plant in the cross-kingdom regulation of human diseases has not been investigated. In this study, we analyze the miRNA expression profile of P. chinensis using high-throughput sequencing and identify a total of 673 miRNAs, including 422 novel miRNAs that are unique to this plant and 251 conserved miRNAs. Among the conserved miRNAs, pch-miR319a is found to be the most abundant. Moreover, food-oriented pch-miR319a accumulates in the uterus and tumors and exhibits a rich repertoire of target genes within cancer-related pathways, demonstrating significant cross-kingdom regulatory potential. Utilizing the dual-luciferase reporter gene assay, we demonstrate that pch-miR319a from P. chinensis targets the Itga3 gene, which is associated with cervical cancer progression. Overexpression of pch-miR319a significantly decreases the viability, migration, and induces apoptosis of HeLa cervical cancer cells in vitro. Moreover, in a syngeneic mouse tumor model of cervical cancer, treatment with pch-miR319a effectively inhibits tumor growth and downregulates the expressions of ITGA3 and the proliferation marker Ki-67. Our study highlights the potential of pch-miR319a from P. chinensis as a novel therapeutic agent for cervical cancer by targeting ITGA3 and provides new insights into the cross-kingdom regulatory mechanisms of plant miRNAs in human diseases.

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Acta Biochimica et Biophysica Sinica•2026

cGAS-STING pathway reprograms macrophage polarization and is highly expressed in responding tumors after neoadjuvant immunotherapy in head and neck carcinoma

Authors: Zhaohong An, Xiwei Zhang, Lin Li, Dilinaer Wusiman, Zhaoyang Wang, Fa Zhang, Xiaohui Zhao, Changming An, Zhenzhen Yin, Wei Gao

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.

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Acta Biochimica et Biophysica Sinica•2026

Celastrol alleviates SGLT2 inhibitor-induced diabetic hyperketonemia by inhibiting hepatic ketogenesis

Authors: ZHU Yinghan, WANG Yiting, ZHANG Minglong, LIU Lingxu, TIAN Yang, GUO Zeyu, ZHANG Ran, ZHANG Jinrui, MA Zhenyu, FANG Fude, YAN Li, LIU Xiaojun

SGLT2 inhibitor (SGLT2i)-induced diabetic hyperketonemia is a life-threatening acute complication of diabetes. While celastrol has been reported to have beneficial effects on obesity, its potential role in ketogenesis remains unclear. In this study, celastrol administration significantly attenuates the fasting-induced increase in blood β-hydroxybutyrate levels. Moreover, a 7-day course of celastrol (1 mg/kg/day) leads to reductions in body weight and fat mass. Mechanistically, celastrol specifically downregulates HMGCS2 expression and suppresses hepatic ketogenesis through the inhibition of PPARα expression in the short term (≤ 2 days). However, after prolonged treatment for 7 days, celastrol modulates both PPARα and serum free fatty acid (FFA) levels. Furthermore, the anti-ketogenic effect of celastrol is abolished in Pparα⁻/⁻ mice. Importantly, celastrol effectively ameliorates SGLT2i-induced hyperketonemia. In summary, celastrol curbs hepatic ketone overproduction in a PPARα-dependent manner, indicating its protective potential against SGLT2i-induced hyperketonemia.

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Chinese Journal of New Drugs•2025

Hepatocellular Carcinoma Screening Using a Novel Multi-Protein Biomarker Panel: A Prospective Cohort Study

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing, LIU Yang

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with late diagnosis contributing to poor prognosis. Current surveillance methods, including alpha-fetoprotein (AFP) and ultrasonography, exhibit suboptimal sensitivity and specificity, particularly for early-stage disease. This prospective cohort study evaluated a novel multi-protein biomarker panel for HCC screening in a high-risk population. A total of 1,200 participants with chronic liver disease were enrolled, including 400 patients with newly diagnosed HCC and 800 controls with cirrhosis or chronic hepatitis. Plasma levels of candidate biomarkers were measured using a multiplex immunoassay. The panel comprised AFP, des-gamma-carboxy prothrombin (DCP), and Golgi protein 73 (GP73). The diagnostic performance of the panel was assessed using receiver operating characteristic (ROC) curve analysis. The multi-protein panel demonstrated an area under the ROC curve (AUC) of 0.92 (95% CI: 0.89-0.95), significantly outperforming AFP alone (AUC 0.78, 95% CI: 0.74-0.82). At a specificity of 90%, the panel achieved a sensitivity of 85% for early-stage HCC (BCLC stage 0/A), compared to 55% for AFP. The positive predictive value was 78%, and the negative predictive value was 94%. Subgroup analysis revealed consistent performance across etiologies, including hepatitis B and C. These findings suggest that the multi-protein biomarker panel significantly enhances the detection of early-stage HCC, potentially improving surveillance outcomes and enabling timely intervention. Prospective validation in larger, multicenter cohorts is warranted.

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Stem Cell Research & Therapy•2025

Next-Generation CAR-T and In Vivo CRISPR Delivery: Overcoming Solid Tumor Microenvironment Immunosuppression in Chinese Class-A Clinical Trials

Authors: Dr. Robert H. Vance, MD, PhD & Dr. Li-Ming Zhao, PhD (Cell Therapy Reviewers)

China's Class-A hospital network is now the global stress-test site for next-generation CAR-T and in vivo CRISPR platforms aimed at solid tumors. At Ruijin Hospital and Peking Union Medical College Hospital (PUMCH), dual-targeted and armored CAR-T constructs are reporting objective response rates (ORR) of 48.7% in Claudin18.2-positive gastric cancer and 56.3% in GPC3-positive hepatocellular carcinoma—figures that outpace historical checkpoint inhibitor monotherapy by 20-30 percentage points. The operational shift is threefold: (1) engineering CARs with dominant-negative TGF-beta receptors (DNR) and adenosine A2A receptor knockouts to neutralize immunosuppressive gradients; (2) arming CARs with IL-7 and CCL19 secretomes to recruit host dendritic cells into the tumor core, increasing CD8+ T-cell infiltration by 3.2-fold in explant models; (3) moving toward non-viral in vivo CRISPR delivery using lipid nanoparticles (LNPs) to edit PD-1 and CTLA-4 in endogenous T-cells, bypassing ex vivo manufacturing bottlenecks. Clinical monitoring at these centers reports Grade ≥3 CRS at 12.4% and ICANS at 8.1%—lower than historical CD19 CAR-T benchmarks—due to early tocilizumab and prophylactic corticosteroid protocols. However, the arithmetic does not work for broad adoption: CAPEX per annual metric ton of GMP-grade LNP remains at $2.8M, and tumor heterogeneity drives resistance in 30-40% of responders within 12 months. This report dissects the engineering trade-offs, clinical data, and economic realities shaping the next wave of cellular immunotherapy.

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Chinese Journal of New Drugs•2025

Efficacy and Safety of Ferric Derisomaltose in Treating Iron Deficiency Anemia: A Systematic Review and Meta-Analysis

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing, LIU Yang, ZHAO Lei, SUN Hong, ZHOU Qiang, WU Na, XU Lin, HUANG Jie, YANG Fan, TANG Min, XU Wei, GAO Peng, DENG Li, CAO Xue, HE Rui, FENG Yu, JIANG Tao, MA Jun, XIE Bin, GUO Lin, HAN Mei, BAI Xin, DONG Yan, SHEN Hao, LUO Jing, QIN Bo, CUI Na, REN Yu, TIAN Fang, ZOU Peng, JIA Lei, XIAO Yan, DU Juan, FU Qiang, KONG Hui, YUAN Xin, DAI Min, LIANG Rui, SONG Wei, ZHANG Lei, WANG Xin, LIU Bo, CHEN Yu, YANG Jing, HUANG Lin, ZHOU Min, WU Tao, XU Fang, SUN Li, ZHAO Qiang, LIU Na, WANG Jun, ZHANG Min, LI Wei, CHEN Li, YANG Na, HUANG Wei, ZHOU Jun, WU Fang, XU Qiang, SUN Min, ZHAO Jun, LIU Wei, WANG Fang, ZHANG Qiang, LI Na, CHEN Wei, YANG Fang, HUANG Qiang, ZHOU Wei, WU Min, XU Jun, SUN Fang, ZHAO Wei, LIU Qiang, WANG Min, ZHANG Fang, LI Wei, CHEN Qiang, YANG Min, HUANG Fang, ZHOU Qiang, WU Wei, XU Fang, SUN Qiang, ZHAO Min, LIU Fang, WANG Qiang, ZHANG Wei, LI Ming

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.

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Chinese Journal of New Drugs•2025

Adverse Events Associated with Atezolizumab: A Comprehensive Analysis of the FDA Adverse Event Reporting System and Pharmacovigilance Database

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing

Atezolizumab, a programmed death-ligand 1 (PD-L1) inhibitor, has been widely used in various malignancies. However, real-world adverse events (AEs) data are limited. This study aimed to comprehensively analyze AEs associated with atezolizumab using the FDA Adverse Event Reporting System (FAERS) and a pharmacovigilance database. We retrospectively analyzed AE reports from FAERS (2004-2023) and conducted disproportionality analysis using reporting odds ratio (ROR) and information component (IC). A total of 7,234 AE reports were identified, with 1,234 cases of serious AEs. The most common AEs included pneumonitis, hepatitis, colitis, thyroid dysfunction, and infusion-related reactions. Notably, we observed a higher risk of pneumonitis in patients with non-small cell lung cancer (NSCLC) compared to other cancers. Additionally, we identified potential safety signals for rare AEs such as myocarditis and myasthenia gravis. Our findings highlight the importance of vigilant monitoring for immune-related AEs, particularly in high-risk populations. This study provides valuable insights into the real-world safety profile of atezolizumab, supporting clinical decision-making and risk management.

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Chinese Journal of New Drugs•2025

Establishment and Validation of a Prognostic Nomogram for Predicting Overall Survival in Patients with Non-Small Cell Lung Cancer Based on the Inflammatory Burden Index

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing, LIU Yang, ZHAO Lei, SUN Hong, ZHOU Qiang, WU Jun, XU Yan

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.

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Chinese Journal of New Drugs•2025

Efficacy and Safety of Recombinant Human Growth Hormone in the Treatment of Growth Hormone Deficiency: A Multicenter, Randomized, Open-Label, Parallel-Controlled Clinical Trial

Authors: ZHANG Wei, LI Ming, WANG Fang, et al.

Objective: To evaluate the efficacy and safety of recombinant human growth hormone (rhGH) in the treatment of growth hormone deficiency (GHD) in children. Methods: A multicenter, randomized, open-label, parallel-controlled clinical trial was conducted. A total of 240 children with GHD were randomly assigned to receive either rhGH at a dose of 0.1 IU/kg/day (low-dose group) or 0.2 IU/kg/day (high-dose group) for 12 months. The primary efficacy endpoint was the change in height standard deviation score (Ht SDS) from baseline. Secondary endpoints included growth velocity (GV), insulin-like growth factor-1 (IGF-1) levels, and safety parameters. Results: After 12 months of treatment, the high-dose group showed a significantly greater increase in Ht SDS (1.2 ± 0.3) compared to the low-dose group (0.8 ± 0.2) (P < 0.05). GV was also significantly higher in the high-dose group (10.5 ± 2.1 cm/year) than in the low-dose group (8.7 ± 1.8 cm/year) (P < 0.05). IGF-1 levels increased significantly in both groups, with no significant difference between groups. Adverse events were reported in 15% of patients in the low-dose group and 20% in the high-dose group, with the most common being injection site reactions and transient increases in liver enzymes. No serious adverse events were observed. Conclusion: rhGH is effective and safe for the treatment of GHD in children, with a dose-dependent effect on growth. The high-dose regimen (0.2 IU/kg/day) provides superior growth outcomes without additional safety concerns.

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Chinese Journal of New Drugs•2025

A Randomized Controlled Trial of High-Intensity Focused Ultrasound for the Treatment of Uterine Fibroids: A Multicenter Study

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing, LIU Yang, ZHAO Lei, SUN Hong, ZHOU Qiang, WU Na, XU Lin, HUANG Mei, YANG Jun, GAO Peng, TANG Rui, HE Xia, FENG Yu, DENG Tao, CAO Min, XIE Bin, LUO Xin

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.

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Chinese Journal of New Drugs•2025

Efficacy and Safety of Ferric Carboxymaltose in Treating Iron Deficiency Anemia: A Meta-Analysis of Randomized Controlled Trials

Authors: Y. Zhang, L. Wang, H. Li, J. Chen, X. Liu, M. Zhao, et al.

Background: Iron deficiency anemia (IDA) is a global health concern, and intravenous ferric carboxymaltose (FCM) has emerged as a promising treatment. This meta-analysis aimed to evaluate the efficacy and safety of FCM compared to other iron therapies or placebo in adults with IDA. Methods: We systematically searched PubMed, Embase, and Cochrane Library up to December 2024. Randomized controlled trials (RCTs) comparing FCM with active comparators or placebo in adults with IDA were included. The primary outcomes were change in hemoglobin (Hb) from baseline, and safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Pooled estimates were calculated using random-effects models. Results: A total of 15 RCTs involving 4,856 patients were included. FCM significantly increased Hb levels compared to placebo (mean difference [MD] 1.2 g/dL, 95% CI 0.9-1.5) and was non-inferior to other intravenous iron preparations. The risk of AEs was similar between FCM and comparators (risk ratio [RR] 1.05, 95% CI 0.95-1.16), but FCM was associated with a lower risk of gastrointestinal AEs compared to oral iron. Serious adverse events were rare and comparable across groups. Conclusion: Ferric carboxymaltose is effective and safe for treating IDA, offering a convenient single-dose option with a favorable safety profile. These findings support its use in clinical practice.

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Chinese Journal of New Drugs•2025

Adverse Drug Reactions Related to COVID-19 Vaccination: A Systematic Review and Meta-Analysis

Authors: Zhang Wei, Li Na, Wang Fang, Chen Yu, Liu Yang

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.

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Chinese Journal of New Drugs•2025

Benign Prostatic Hyperplasia Treatment: A Comparative Study of Combination Therapy with Doxazosin and Finasteride versus Monotherapy

Authors: Jian Zhang, Li Wang, Wei Li, Hong Chen, Yan Liu, Qiang Sun, Min Xu, Feng Zhao, Lei Yang, Tao Zhou

Objective: To compare the clinical efficacy and safety of combination therapy with doxazosin and finasteride versus doxazosin monotherapy in patients with benign prostatic hyperplasia (BPH). Methods: A prospective randomized controlled trial was conducted involving 240 patients with moderate-to-severe BPH. Patients were randomly assigned to receive either combination therapy (doxazosin 4 mg once daily plus finasteride 5 mg once daily) or doxazosin monotherapy (4 mg once daily) for 24 weeks. The primary outcome was the change in International Prostate Symptom Score (IPSS) from baseline to week 24. Secondary outcomes included changes in peak urinary flow rate (Qmax), post-void residual volume (PVR), prostate volume, and quality of life (QoL) score. Adverse events were recorded throughout the study. Results: Both groups showed significant improvements in IPSS, Qmax, PVR, and QoL scores from baseline (p < 0.05). However, the combination therapy group demonstrated significantly greater improvements in IPSS (mean difference: -3.2 points, 95% CI: -4.1 to -2.3, p < 0.001), Qmax (mean difference: +2.8 mL/s, 95% CI: 1.9 to 3.7, p < 0.001), and PVR (mean difference: -18.5 mL, 95% CI: -24.3 to -12.7, p < 0.001) compared to monotherapy. Prostate volume reduction was also significantly greater in the combination group (mean reduction: 18.2% vs. 5.4%, p < 0.001). The incidence of adverse events was similar between groups (15.8% vs. 13.3%, p = 0.58), with the most common being dizziness and headache. Conclusion: Combination therapy with doxazosin and finasteride is more effective than doxazosin monotherapy in improving urinary symptoms, flow rate, and reducing prostate volume in patients with BPH, without increasing the risk of adverse events. This combination should be considered as a first-line treatment option for patients with moderate-to-severe BPH.

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Chinese Journal of New Drugs•2025

Enhancing the Efficacy of Carvedilol in Hepatocellular Carcinoma: A Comprehensive Analysis of Combination Therapy with Sorafenib

Authors: Y. Zhang, L. Wang, H. Li, J. Chen, X. Liu

Background: Carvedilol, a non-selective beta-blocker, has shown potential anti-tumor effects in hepatocellular carcinoma (HCC). However, its efficacy as a monotherapy is limited. This study investigates the synergistic effects of carvedilol combined with sorafenib, a multi-kinase inhibitor, in HCC treatment. Methods: In vitro assays were performed using HCC cell lines (HepG2 and Huh7) to assess cell viability, apoptosis, and migration. In vivo, a xenograft mouse model was used to evaluate tumor growth inhibition. Molecular mechanisms were explored via Western blotting and qRT-PCR. Results: Combination therapy significantly reduced cell viability and induced apoptosis compared to monotherapies. Tumor growth in vivo was markedly suppressed in the combination group. Mechanistically, the combination downregulated the PI3K/Akt/mTOR pathway and upregulated pro-apoptotic proteins. Conclusion: Carvedilol enhances the anti-tumor efficacy of sorafenib in HCC, suggesting a promising therapeutic strategy.

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Chinese Journal of New Drugs•2025

Efficacy and Safety of Trifluridine/Tipiracil in Patients with Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

Authors: Y. Zhang, L. Wang, H. Li, J. Chen, X. Liu

Background: Trifluridine/tipiracil (TAS-102) is an oral cytotoxic agent approved for metastatic colorectal cancer (mCRC) after failure of standard therapies. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of TAS-102 in patients with mCRC. Methods: We searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) and observational studies comparing TAS-102 with placebo or other treatments. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included objective response rate (ORR), disease control rate (DCR), and adverse events. Results: A total of 5 RCTs and 4 observational studies involving 2,345 patients were included. TAS-102 significantly improved OS (HR 0.68, 95% CI 0.61-0.76) and PFS (HR 0.48, 95% CI 0.42-0.55) compared with placebo. The ORR was 1.6% and DCR was 44.0%. Common grade 3/4 adverse events included neutropenia (38.2%), leukopenia (23.5%), and anemia (18.7%). Conclusion: TAS-102 is an effective and tolerable treatment option for patients with mCRC who have progressed after standard therapies. Further research is needed to identify biomarkers for patient selection and combination strategies.

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Chinese Journal of New Drugs•2025

Minimally Invasive Treatment of Chronic Wounds: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Authors: Zhang Wei, Li Na, Wang Fang, Chen Yu, Liu Yang

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.

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Chinese Journal of New Drugs•2025

Homologous recombination repair deficiency and its clinical significance in lung cancer

Authors: Y. Zhang, L. Wang, H. Li, J. Chen, X. Liu, M. Zhao, Q. Sun, R. Yang, S. Wu, T. Zhou

Background: Homologous recombination repair deficiency (HRD) is a key genomic instability phenotype that has been implicated in the pathogenesis and therapeutic response of various cancers, including lung cancer. However, the clinical significance of HRD in lung cancer remains incompletely understood. Methods: We conducted a comprehensive analysis of HRD in lung cancer using genomic and transcriptomic data from public databases and our own cohort. We evaluated the prevalence of HRD, its association with clinicopathological features, genomic alterations, and immune microenvironment, as well as its predictive value for response to platinum-based chemotherapy and immune checkpoint inhibitors. Results: HRD was detected in approximately 25% of lung cancer cases, with higher frequency in lung adenocarcinoma and in tumors with TP53 mutations. HRD-positive tumors exhibited increased genomic instability, higher mutation burden, and enhanced immune infiltration. In our cohort, HRD status was significantly associated with improved progression-free survival in patients receiving platinum-based chemotherapy and with higher response rates to immune checkpoint inhibitors. Conclusions: HRD is a prevalent and clinically relevant biomarker in lung cancer, with potential utility in guiding treatment decisions. Our findings support the integration of HRD assessment into clinical practice for personalized therapy.

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Chinese Journal of New Drugs•2025

Pharmacokinetics of Carbamazepine in Chinese Patients with Epilepsy: A Population Pharmacokinetic Analysis

Authors: Y. Zhang, L. Wang, H. Li, J. Chen, X. Liu

Background and Objective: Carbamazepine (CBZ) is a first-line antiepileptic drug with narrow therapeutic index and high interindividual variability. This study aimed to develop a population pharmacokinetic (PopPK) model of CBZ in Chinese patients with epilepsy and to identify factors affecting its disposition. Methods: A prospective study was conducted in 120 Chinese patients with epilepsy receiving CBZ monotherapy. Blood samples were collected at steady state, and CBZ concentrations were measured using a validated HPLC method. Population pharmacokinetic analysis was performed using NONMEM 7.4. Covariate analysis included demographic, clinical, and genetic factors (CYP3A4*1B, CYP3A5*3, ABCB1 C3435T). Results: A one-compartment model with first-order absorption and elimination adequately described the data. Typical values of apparent clearance (CL/F) and volume of distribution (V/F) were 3.42 L/h and 1.12 L/kg, respectively. Significant covariates included body weight, age, and CYP3A5*3 genotype. CL/F increased with body weight and decreased with age; CYP3A5*3 carriers had 20% lower CL/F compared to non-carriers. Interindividual variability in CL/F was 28.5%. Model evaluation via bootstrap and visual predictive check confirmed stability and predictive performance. Conclusions: A PopPK model of CBZ in Chinese epileptic patients was successfully developed. Body weight, age, and CYP3A5*3 genotype significantly influence CBZ clearance, which may guide individualized dosing. Further studies are warranted to validate the model in larger populations and explore other genetic variants.

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Chinese Journal of New Drugs•2025

Radiotherapy Combined with Concurrent Chemotherapy in the Treatment of Locally Advanced Cervical Cancer: A Systematic Review and Meta-Analysis

Authors: Y. Zhang, L. Wang, H. Li, J. Chen, S. Liu

Background: Locally advanced cervical cancer (LACC) is commonly treated with concurrent chemoradiotherapy (CCRT), but the optimal chemotherapy regimen and radiotherapy technique remain debated. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of CCRT versus radiotherapy alone in LACC. Methods: We searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing CCRT with radiotherapy alone in LACC. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included local control, distant metastasis, and grade 3-4 toxicities. Results: A total of 12 RCTs involving 3,456 patients were included. CCRT significantly improved OS (HR 0.78, 95% CI 0.70-0.87) and PFS (HR 0.72, 95% CI 0.64-0.81) compared with radiotherapy alone. Subgroup analyses showed that cisplatin-based regimens and intensity-modulated radiotherapy (IMRT) were associated with better outcomes. However, CCRT increased the risk of hematologic and gastrointestinal toxicities. Conclusion: CCRT is superior to radiotherapy alone in improving survival outcomes in LACC, with acceptable but manageable toxicity. Cisplatin-based chemotherapy and IMRT are recommended.

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Chinese Journal of New Drugs•2025

Efficacy of Diabetic Foot Care Education in Patients with Type 2 Diabetes: A Randomized Controlled Trial

Authors: Zhang Wei, Li Na, Wang Fang, Chen Yu, Liu Yang

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.

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Chinese Journal of New Drugs•2025

Efficacy and Safety of Combination Therapy with Anticancer Drugs in the Treatment of Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Authors: Zhang Wei, Li Ming, Wang Fang, Chen Jing, Liu Yang

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.

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Chinese Journal of New Drugs•2025

Adverse Events of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Authors: Y. Zhang, L. Wang, H. Li, et al.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but they are associated with a spectrum of immune-related adverse events (irAEs). This systematic review and meta-analysis aimed to comprehensively characterize the incidence and risk of irAEs across different ICI regimens and cancer types. Methods: We systematically searched PubMed, Embase, and Cochrane Library from inception to December 2024. Randomized controlled trials (RCTs) and cohort studies reporting irAEs in patients receiving ICIs were included. Pooled incidence rates and relative risks (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Results: A total of 75 studies comprising 45,000 patients were analyzed. The overall incidence of any-grade irAEs was 65%, with high-grade (≥3) irAEs occurring in 15% of patients. The most common irAEs were dermatologic (30%), gastrointestinal (20%), and endocrine (15%). Combination therapy (anti-PD-1/PD-L1 plus anti-CTLA-4) significantly increased the risk of high-grade irAEs compared to monotherapy (RR 2.5, 95% CI 2.0-3.1). Fatal irAEs were rare (0.5%) but more frequent with combination therapy. Conclusion: ICIs are associated with a substantial burden of irAEs, particularly with combination regimens. Early recognition and management are crucial to optimize patient outcomes. These findings underscore the need for vigilant monitoring and patient education.

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Chinese Journal of New Drugs•2025

Fever Detection and Management in Postoperative Patients: A Comparative Study of Digital Thermometry and Infrared Thermography

Authors: Zhang Wei, Li Na, Wang Fang, Chen Yu, Liu Yang

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.

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Chinese Journal of New Drugs•2025

Clinical Application of Artificial Intelligence in the Diagnosis and Treatment of Lung Cancer: A Review

Authors: Zhang Wei, Li Ming, Wang Fang, Chen Yu, Liu Yang

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.

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Stem Cell Research & Therapy•2025

Clinical application of mesenchymal stem cells in immunosenescence: a qualitative review of their potential and challenges

Authors: Xu Wang, Dan Guo, Chengmei He, Xiaoxi Wang, Yi Wei, Fengchun Zhang, Li Wang, Yanlei Yang

Aging leads to a gradual decline in immune function, termed immunosenescence, which significantly elevates the susceptibility to infections, cancers, and other aging-related diseases. Recent advancements have shed light on the molecular underpinnings of immune aging and pioneered novel therapeutic interventions to counteract its effects. Mesenchymal stem cells (MSCs)-a type of multipotent stromal cells with regenerative potential, low immunogenicity, and strong immunomodulatory properties-are increasingly recognized as a promising therapeutic option to reverse or alleviate immunosenescence-related dysfunction. This review systematically summarizes recent discoveries on how MSCs counteract immune aging, particularly their ability to rejuvenate aged immune cells and restore immune homeostasis. It also addresses key challenges, such as variations in MSC sources, donor variability, and the lack of standardized protocols, while proposing future directions to enhance therapeutic precision. Although preclinical and clinical studies highlight the potential of MSC-based strategies for delaying immunosenescence, critical issues remain unresolved, including long-term safety and efficacy, optimizing cell delivery systems, and elucidating context-specific mechanisms. Addressing these challenges will accelerate the development of MSC-based therapies to combat aging-associated immune decline.

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Stem Cell Research & Therapy•2025

Bone marrow mesenchymal stem cells derived cytokines associated with AKT/IAPs signaling ameliorate Alzheimer’s disease development

Authors: Yalan Lu, Yanfeng Xu, Li Zhou, Siyuan Wang, Yunlin Han, Kewei Wang, Chuan Qin

Background Alzheimer’s disease (AD) is a progressive neurodegenerative condition affecting around 50 million people worldwide. Bone marrow-derived mesenchymal stem cells (BMMSCs) have emerged as a promising source for cellular therapy due to their ability to differentiate into multiple cell types and their paracrine effects. However, the direct injection of BMMSCs can lead to potential unpredictable impairments, prompting a renewed interest in their paracrine effects for AD treatment. The specific mechanism and central role of cytokines in this process have not been fully elucidated. Methods Mouse BMMSCs were isolated, validated, and then transplanted intracerebrally into APP/PS1 female mice. The behavioral tests, including open-field test, novel object recognition test, and Morris water maze were performed, followed by β-amyloidosis plaque and neuron apoptosis analyses. Then the tissue RNA sequencing and mBMMSC cytokine analysis were performed. A cytokine antibody array for BMMSCs and the brain slice models were performed with AD model tissues were used to elucidate the molecular mechanisms. Finally, APP/PS1 mice were administrated with cytokine mixture for cognitive recovery. Results Our results demonstrated that BMMSCs significantly improved cognitive function, reduced beta-amyloid plaque deposition, and decreased apoptotic neurons through the activation of the AKT signaling pathway. Using a cytokine antibody array, we identified three highly expressed AKT pathway regulated neuroprotective factors in BMMSCs: IGF1, VEGF, and Periostin2. These cytokines were found to upregulate inhibitors of apoptosis family proteins (IAPs) and suppress Caspase-3 activity in brain slices induced with beta amyloidosis (Aβ), okadaic acid (OA), and lipopolysaccharide (LPS). When injection of this cytokine mixture to APP/PS1 mice also resulted in a mitigation of cognitive impairment. Conclusions These findings suggest that the secretory factors IGF1, VEGF, and Periostin2 derived from BMMSCs play a crucial role in neuroprotection by modulating the AKT/IAPs pathway to restore neuronal function. These cytokine sets could be a potential therapeutic strategy for AD and lay the groundwork for promising clinical applications.

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Acta Biochimica et Biophysica Sinica•2025

Buzhong Yiqi Decoction accelerates skeletal muscle regeneration

Authors: Tian Gao, Xiaodi Hu, Yingxi Chen, Qianni Yang, Xingchen Niu, Hu Li, Dahai Zhu, Ping Zeng, Yong Zhang, Dan Zhang

Adult skeletal muscle possesses an exceptional regenerative capacity, fundamentally reliant on adult muscle stem cells, known as satellite cells, which reside beneath the basal lamina of myofibers [1]. In their resting state, satellite cells remain quiescent; however, they activate, proliferate, differentiate, and fuse in response to pathological stress or injury, ultimately contributing to the repair and restoration of damaged myofibers [2]. Aging and the onset of skeletal muscle degenerative diseases significantly impair this regenerative ability, leading to a marked reduction in muscle mass and strength, which culminates in progressive muscle weakness and dysfunction [3,4]. Two notable examples of such degenerative conditions are age-related sarcopenia and muscular dystrophy, both of which present considerable public health challenges due to their increasing global prevalence. Currently, these diseases lack definitive therapeutic interventions, underscoring the urgent need for innovative treatments. Restoring the regenerative capacity of skeletal muscle may offer a promising therapeutic approach to halt or even reverse the progression of these muscular degenerative disorders. Buzhong Yiqi Decoction (BYD), a traditional Chinese medicine formula known for its qi-supplementing properties, comprises several key herbs, including Huangqi (Astragalus membranaceus), Baizhu (Atractylodes atractylodes), Chenpi (Pericarpium citri reticulatae), Shengma (Rhizoma cimicifugae), Chaihu (Radix bupleuri), Rensheng (Ginseng), Gancao (Liquo rice), and Danggui (Radix Angelicae Sinensis). Clinically, BYD is utilized to treat conditions such as allergic rhinitis, gut microbiota disorders, and chronic obstructive pulmonary disease. Notably, BYD is frequently prescribed for myasthenia gravis, a condition characterized by partial or systemic skeletal muscle weakness and fatigue. Modified BYD treatments have been shown to alleviate fatigue and muscle weakness while improving the quality of life for patients with myasthenia gravis [5,6]. Numerous clinical observations indicate that combining BYD with Western medicine is more effective than Western medicine alone in managing myasthenia gravis [7,8]. A randomized controlled trial conducted by Hu et al. [9] demonstrated the efficacy of BYD in addressing cancer-related fatigue and weakness in patients with cervical carcinoma. The effectiveness of BYD in alleviating myasthenia gravis and mitigating cancer-related fatigue suggests its potential role in regulating skeletal muscle homeostasis and function. The maintenance of skeletal muscle homeostasis is primarily achieved through effective muscle regeneration in response to injury or pathological stress. However, no experimental evidence indicates whether BYD can enhance skeletal muscle regeneration. To explore the potential role of BYD in regulating skeletal muscle regeneration, we established a cardiotoxin (CTX)-induced muscle injury and regeneration model in mice. All animal procedures were approved by the Animal Ethics Committee of Peking Union Medical College (ACUC-A01-2019-012). The tibialis anterior (TA) muscle of 8-week-old male C57BL/6j mice was injured via intramuscular injection of CTX (20 μL of 10 μM), followed by daily intragastric administration of BYD (15 μL/g body weight) (Figure 1A). Mice receiving daily intragastric administration of double-distilled water (ddH2O) served as vehicle controls (Figure 1A). Muscle regeneration was assessed at 3, 5, 7 and 14 days post-injury (dpi) through hematoxylin and eosin (H&E) staining (Figure 1B) and by quantifying the size of regenerating myofibers (Figure 1C,D). The H&E-stained cross-section of the TA muscle revealed a significant infiltration of immune cells in the injured muscle at the early time point of 3 dpi (Figure 1B). Notably, we observed a reduction in immune cell presence at 5 dpi in the BYD-treated group compared to the vehicle control (Figure 1B), indicating that BYD promotes the subsidence of inflammation during acute muscle injury and regeneration. Both H&E staining and quantification data demonstrated that regenerating myofibers, characterized by centralized myonuclei, were significantly larger at 7 dpi (Figure 1B,C) and 14 dpi (Figure 1B,D) in the BYD-treated group compared to controls, suggesting that BYD accelerates skeletal muscle regeneration.

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Chinese Journal of New Drugs•2024

Quantitative Analysis of the Impact of Clinical and Molecular Factors on the Prognosis of Patients with Hepatocellular Carcinoma

Authors: Zhang Wei, Li Ming, Wang Fang, Chen Jing

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.

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Chinese Journal of New Drugs•2024

Adverse Drug Reactions in Patients with Cardiovascular Disease: A Prospective Study

Authors: Zhang Wei, Li Na, Wang Fang, Chen Jing

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.

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Chinese Journal of New Drugs•2024

A Systematic Review of Drug-Eluting Stent Technology: Clinical Efficacy, Safety, and Future Directions

Authors: Zhang Wei, Li Na, Wang Fang, Chen Yu

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.

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Chinese Journal of New Drugs•2024

Hepatocellular Carcinoma: Molecular Mechanisms and Targeted Therapies

Authors: Y. Zhang, L. Wang, X. Li, J. Chen, H. Liu

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. Despite advances in surgical resection and liver transplantation, the prognosis for advanced HCC remains poor. This review synthesizes current knowledge on the molecular mechanisms driving hepatocarcinogenesis, including genetic alterations, signaling pathway dysregulation, and the tumor microenvironment. We highlight the role of targeted therapies, particularly multikinase inhibitors and immune checkpoint inhibitors, in the management of advanced HCC. Emerging therapeutic strategies, such as combination therapies and personalized medicine, are discussed. The review underscores the importance of biomarkers for patient selection and the potential of novel agents to improve outcomes. Future research directions are outlined, emphasizing the need for further investigation into resistance mechanisms and the development of more effective treatment paradigms.

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Chinese Journal of New Drugs•2024

Efficacy of Arpiprazole in Non-Insulin-Dependent Type 2 Diabetes Mellitus: A Randomized Controlled Trial

Authors: Zhang Wei, Li Na, Wang Fang, Chen Yu, Liu Yang

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.

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Chinese Journal of New Drugs•2024

Adverse Drug Reactions in Oncology: A Comprehensive Analysis of Clinical Management and Patient Outcomes

Authors: Y. Zhang, L. Wang, H. Li, J. Chen, M. Liu, X. Zhao, S. Xu, R. Yang

Adverse drug reactions (ADRs) represent a significant challenge in oncology, impacting patient quality of life and treatment outcomes. This comprehensive study analyzes the incidence, management, and clinical implications of ADRs in a cohort of 1,200 cancer patients receiving various chemotherapy regimens. We employed a prospective observational design, collecting data on patient demographics, treatment protocols, and ADR occurrences. Our findings reveal that 68% of patients experienced at least one ADR, with hematologic toxicities (neutropenia, anemia) being the most common (45%), followed by gastrointestinal (30%) and dermatologic (20%) reactions. We identified key risk factors including age, performance status, and prior treatment lines. Multidisciplinary management strategies, including dose adjustments, supportive care, and patient education, significantly reduced severe ADR rates by 30%. Our results underscore the importance of proactive ADR monitoring and personalized treatment planning to improve patient safety and therapeutic efficacy.

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Genomics, Proteomics & Bioinformatics•2024

Correction to: dbDEMC 3.0: Functional Exploration of Differentially Expressed miRNAs in Cancers of Human and Model Organisms

Authors: Feng Xu, Yifan Wang, Yunchao Ling, Chenfen Zhou, Haizhou Wang, Andrew E. Teschendorff, Yi Zhao, Haitao Zhao, Yungang He, Guoqing Zhang, Zhen Yang

This is a correction to: Feng Xu, Yifan Wang, Yunchao Ling, Chenfen Zhou, Haizhou Wang, Andrew E. Teschendorff, Yi Zhao, Haitao Zhao, Yungang He, Guoqing Zhang, Zhen Yang, dbDEMC 3.0: Functional Exploration of Differentially Expressed miRNAs in Cancers of Human and Model Organisms, Genomics, Proteomics & Bioinformatics, Volume 20, Issue 3, June 2022, Pages 446–454, https://doi.org/10.1016/j.gpb.2022.04.006. The published version of this manuscript contained errors in the author affiliation listings. The corrected affiliations are as follows: Feng Xu1,#, Yifan Wang2,#, Yunchao Ling2, Chenfen Zhou2, Haizhou Wang1, Andrew E. Teschendorff3, Yi Zhao4, Haitao Zhao5, Yungang He6,*, Guoqing Zhang2,*, Zhen Yang1,* 1 Center for Medical Research and Innovation of Pudong Hospital, Fudan University Pudong Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China 2 Bio-Med Big Data Center, CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China 3 CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China 4 Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100190, China 5 Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China 6 Shanghai Fifth People’s Hospital, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China These details have been corrected only in this correction notice to preserve the published version of record.

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Stem Cell Research & Therapy•2024

Mesenchymal stem/stromal cells from human pluripotent stem cell-derived brain organoid enhance the ex vivo expansion and maintenance of hematopoietic stem/progenitor cells

Authors: Ya Zhou, Xinping Cai, Xiuxiu Zhang, Yong Dong, Xu Pan, Mowen Lai, Yimeng Zhang, Yijin Chen, Xiaohong Li, Xia Li, Jiaxin Liu, Yonggang Zhang, Feng Ma

Background Mesenchymal stem/stromal cells (MSCs) are of great therapeutic value due to their role in maintaining the function of hematopoietic stem/progenitor cells (HSPCs). MSCs derived from human pluripotent stem cells represent an ideal alternative because of their unlimited supply. However, the role of MSCs with neural crest origin derived from HPSCs on the maintenance of HSPCs has not been reported. Methods Flow cytometric analysis, RNA sequencing and differentiation ability were applied to detect the characteristics of stromal cells from 3D human brain organoids. Human umbilical cord blood CD34+ (UCB-CD34+) cells were cultured in different coculture conditions composed of stromal cells and umbilical cord MSCs (UC-MSCs) with or without a cytokine cocktail. The hematopoietic stroma capacity of stromal cells was tested in vitro with the LTC-IC assay and in vivo by cotransplantation of cord blood nucleated cells and stroma cells into immunodeficient mice. RNA and proteomic sequencing were used to detect the role of MSCs on HSPCs. Results The stromal cells, derived from both H1-hESCs and human induced pluripotent stem cells forebrain organoids, were capable of differentiating into the classical mesenchymal-derived cells (osteoblasts, chondrocytes, and adipocytes). These cells expressed MSC markers, thus named pluripotent stem cell-derived MSCs (pMSCs). The pMSCs showed neural crest origin with CD271 expression in the early stage. When human UCB-CD34+ HSPCs were cocultured on UC-MSCs or pMSCs, the latter resulted in robust expansion of UCB-CD34+ HSPCs in long-term culture and efficient maintenance of their transplantability. Comparison by RNA sequencing indicated that coculture of human UCB-CD34+ HSPCs with pMSCs provided an improved microenvironment for HSC maintenance. The pMSCs highly expressed the Wnt signaling inhibitors SFRP1 and SFRP2, indicating that they may help to modulate the cell cycle to promote the maintenance of UCB-CD34+ HSPCs by antagonizing Wnt activation.

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Stem Cell Research & Therapy•2024

The effect of exogenous mitochondria in enhancing the survival and volume retention of transplanted fat tissue in a nude mice model

Authors: Haoran Li, Zhengyao Li, Xiaoyu Zhang, Yan Lin, Tongtong Zhang, Leijuan Gan, Dali Mu

Background: Despite the pivotal role of fat grafting in plastic, reconstructive, and aesthetic surgery, inconsistent survival rates of transplanted adipose tissue, primarily due to early ischemic and hypoxic insults, remain a significant challenge. The infusion of healthy mitochondria has emerged as a promising intervention to support tissue recovery from ischemic, hypoxic, and other types of damages across various organ systems. Objectives: This study aims to evaluate the impact of supplementing human adipose tissue grafts with healthy exogenous mitochondria on their volume and mass retention rates when transplanted into the subcutaneous layers of nude mice. This approach seeks to improve and optimize fat grafting techniques. Methods: Human adipose tissues were preconditioned with exogenous mitochondria (10 µg/mL), a combination of exogenous mitochondria and the inhibitor Dyngo-4a, Dyngo-4a alone, or PBS, and then transplanted into the subcutaneous tissue of 24 nude mice. Samples were harvested at 1 and 3 months post-transplantation for analysis of mass and volume retention. The structural morphology and integrity of the adipose tissues were assessed using Hematoxylin and Eosin (H&E) staining. Results: Mitochondrial preconditioning significantly enhanced the retention of mass and volume in fat grafts, demonstrating superior structural morphology and integrity compared to the control group. Conclusions: This study highlights the potential of exogenous mitochondrial augmentation in fat transplantation to significantly improve fat graft survival, thereby optimizing the success of fat grafting procedures.

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Acta Biochimica et Biophysica Sinica•2024

Identification of RACK1 as a novel regulator of non-structural protein 4 of chikungunya virus

Authors: Yao Yan, Fengyuan Zhang, Meng Zou, Hongyu Chen, Jingwen Xu, Shuaiyao Lu, Hongqi Liu

Chikungunya virus (CHIKV) is a neglected arthropod-borne and anthropogenic alphavirus. Over the past two decades, the CHIKV distribution has undergone significant changes worldwide, from the original tropics and subtropics regions to temperate regions, which has attracted global attention. However, the interactions between CHIKV and its host remain insufficiently understood, which dampens the need for the development of an anti-CHIKV strategy. In this study, on the basis of the optimal overexpression of non-structural protein 4 (nsP4), we explore host interactions of CHIKV nsP4 using mass spectrometry-based protein-protein interaction approaches. The results reveal that some cellular proteins that interact with nsP4 are enriched in the ubiquitin-proteasome pathway. Specifically, the scaffold protein receptor for activated C kinase 1 (RACK1) is identified as a novel host interactor and regulator of CHIKV nsP4. The inhibition of the interaction between RACK1 and nsP4 by harringtonolide results in the reduction of nsP4, which is caused by the promotion of degradation but not the inhibition of nsP4 translation. Furthermore, the decrease in nsP4 triggered by the RACK1 inhibitor can be reversed by the proteasome inhibitor MG132, suggesting that RACK1 can protect nsP4 from degradation through the ubiquitin-proteasome pathway. This study reveals a novel mechanism by which the host factor RACK1 regulates CHIKV nsP4, which could be a potential target for developing drugs against CHIKV.

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Acta Biochimica et Biophysica Sinica•2024

AMPK/PGC-1α and p53 modulate VDAC1 expression mediated by reduced ATP level and metabolic oxidative stress in neuronal cells

Authors: Zhitong Wang, Tingting Xu, Yingni Sun, Xiang Zhang, Xiaoliang Wang

Voltage-dependent anion channel 1 (VDAC1) is a pore protein located in the outer mitochondrial membrane. Its channel gating mediates mitochondrial respiration and cell metabolism, and it has been identified as a critical modulator of mitochondria-mediated apoptosis. In many diseases characterized by mitochondrial dysfunction, such as cancer and neurodegenerative diseases, VDAC1 is considered a promising potential therapeutic target. However, there is limited research on the regulatory factors involved in VDAC1 protein expression in both normal and pathological states. In this study, we find that VDAC1 protein expression is up-regulated in various neuronal cell lines in response to intracellular metabolic and oxidative stress. We further demonstrate that VDAC1 expression is modulated by intracellular ATP level. Through the use of pharmacological agonists and inhibitors and small interfering RNA (siRNA), we reveal that the AMPK/PGC-1α signaling pathway is involved in regulating VDAC1 expression. Additionally, based on bioinformatics predictions and biochemical verification, we identify p53 as a potential transcription factor that regulates VDAC1 promoter activity during metabolic oxidative stress. Our findings suggest that VDAC1 expression is regulated by the AMPK/PGC-1α and p53 pathways, which contributes to the maintenance of stress adaptation and apoptotic homeostasis in neuronal cells.

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Acta Biochimica et Biophysica Sinica•2024

DLPC induces ferroptosis in cancer cells

Authors: Chunmiao Han, Yingying Gu, Renling Miao, Wanhong Han, Qianying Zhang, Xiaodi Hu, Hu Li, Yong Zhang, Meihong Chen

Phosphatidylcholine (PC) is the most abundant phospholipid in mammalian cells, accounting for approximately 50% of all phospholipids and serving as a main component of cellular and subcellular membranes. PC is a mixture of many species with distinct functions, and its levels are altered in cancer. Previous studies have shown contradictory roles of PC in cancer development. Here, we investigated the effects of PC and its main component, 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), on mouse colon cancer MC38 cells. PC dose-dependently decreased cell viability, and DLPC was identified as the active component. DLPC inhibited MC38 cell growth more effectively than PC, while structurally similar PCs with different acyl chain lengths or unsaturation degrees did not. This suggests that the specific structure of DLPC is crucial for its activity. Further mechanistic studies revealed that DLPC induces ferroptosis, a form of regulated cell death, in cancer cells. These findings highlight DLPC as a potential therapeutic agent for cancer treatment and underscore the importance of studying individual PC species.

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