Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences最新文献

{"title":"[Application of polygenic risk score-based comprehensive breast cancer risk assessment in preimplantation embryo selection for a <i>BRCA1</i> mutation carrier].","authors":"Yinghui Ye, Xiaoling Hu, Kai Yan, Jialing Yu, Yulin Chen, Yangyun Zou, Qiong Luo, Dan Zhang, Yimin Zhu, Hefeng Huang","doi":"10.3724/zdxbyxb-2025-0898","DOIUrl":"10.3724/zdxbyxb-2025-0898","url":null,"abstract":"<p><p>A patient, whose family carried a <i>BRCA1</i>: c.5154G>A pathogenic variant, had experienced infertility for three years and sought assisted reproductive technology. We constructed a breast cancer polygenic risk score (PRS)-313 model by integrating genetic data from breast cancer patients and controls in the UK Biobank with Asian population-specific single nucleotide polymorphism weights. Following controlled ovarian stimulation, embryo culture, and biopsy, the embryos were tested for the <i>BRCA1</i> pathogenic variant. By integrating the breast cancer PRS‑313 score and family history of breast cancer, a comprehensive breast cancer risk assessment was obtained for each embryo. Based on these assessments, together with chromosomal testing results and embryonic development status, the most suitable embryo was selected for transfer. The patient achieved a successful pregnancy and delivered a live-born infant who did not carry the <i>BRCA1</i>: c.5154G>A mutation.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"475-482"},"PeriodicalIF":0.0,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148139266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[<i>Cuscuta chinensis</i> Lam. reduces oxidative injury in Alzheimer<b>'</b>s disease model cells].","authors":"Deyu Li, Xin Liu, Yunwei Lu, Guran Yu","doi":"10.3724/zdxbyxb-2025-0418","DOIUrl":"10.3724/zdxbyxb-2025-0418","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the protective effect of <i>Cuscuta chinensis</i> Lam. against oxidative injury in an Alzheimer's disease (AD) cell model, as well as the related molecular mechanism.</p><p><strong>Methods: </strong>Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to analyze and identify the chemical components of <i>Cuscuta chinensis</i> Lam.. An oxidative injury model was established in HT22 neuronal cells treated with Aβ_1-42. Cell viability was measured by CCK-8 assay, and apoptosis was detected by Annexin V-FITC/PI double staining. Intracellular reactive oxygen species (ROS) levels were detected using the DCFH-DA probe, and the expression of antioxidant- and apoptosis-related proteins was examined by Western blotting.</p><p><strong>Results: </strong>A total of 381 chemical components were identified from <i>Cuscuta chinensis</i> Lam., among which astragalin, hyperoside, kaempferol, and quercetin were the main constituents. Cell experi-ments showed that <i>Cuscuta chinensis</i> Lam. at concentrations of 0.50, 0.75, and 1.00 mg/mL increased the viability of Aβ_1-42‑treated HT22 cells, decreased the apoptosis rate, inhibited ROS excessive accumulation, upregulated the expression of the antioxidant-related proteins heme oxygenase-1 and NQO1, downregulated the expression of the apoptosis-related protein cytochrome C, and reduced the ratios of activated caspase-3/caspase-3 and BAX/Bcl-2.</p><p><strong>Conclusions: </strong><i>Cuscuta chinensis</i> Lam. may attenuate oxidative injury in AD model cells by activating the endogenous antioxidant defense system and inhibiting the mitochondrial-dependent apoptotic pathway.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"404-413"},"PeriodicalIF":0.0,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148200145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Research progress on vascular endothelial growth factor C in meningeal lymphatic vessel-mediated clearance of amyloid β-protein].","authors":"Zhaoxie Yu, Yao Wang, Yanan Li, Feng Shen, Yanchun Wang","doi":"10.3724/zdxbyxb-2025-0549","DOIUrl":"10.3724/zdxbyxb-2025-0549","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the abnormal deposition of amyloid β-protein (Aβ) as a core pathological feature. Meningeal lymphatic vessels are crucial for Aβ clearance, and their dysfunction accelerates AD progression. Vascular endothelial growth factor C (VEGF-C), through activation of vascular endothelial growth factor receptor 3 and downstream pathways, synergistically promotes lymphangiogenesis, enhances lymphatic permeability, and regulates lymphatic fluid flow, thereby improving Aβ clearance efficiency. Genetic factors and aging-related declines in VEGF-C further impair meningeal lymphatic function, creating a vicious cycle. This review summarizes the mechanisms by which VEGF-C regulates the structure and function of meningeal lymphatic to promote Aβ clearance, synthesizes the evidence that genetic factors and aging contribute to meningeal lymphatic dysfunction through their effects on VEGF-C, and discusses the prospects of individualized intervention strategies for Alzheimer's disease based on VEGF-C-mediated modulation of meningeal lymphatics, aiming to provide insights for AD prevention and treatment.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"383-390"},"PeriodicalIF":0.0,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[DOT1L controls neuronal amyloid precursor protein expres-sion via the p38 MAPK-mediated mitochondrial dynamics homeostasis axis].","authors":"Yumin Zhang, Feiyu Zhu, Xiaotian Wu, Zhansong Li, Peng Huang, Yanpan Gao, Linghui Zeng","doi":"10.3724/zdxbyxb-2025-0706","DOIUrl":"10.3724/zdxbyxb-2025-0706","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To investigate the regulatory role of epigenetic regulator disruptor of telomeric silencing 1-like (DOT1L) and its mediated histone H3 lysine 79 (H3K79) methylation in modulating neuronal amyloid precursor protein (APP) expression, and to elucidate the underlying mechanisms involving mitochondrial dynamics homeo-stasis and the upstream p38 mitogen-activated protein kinase (p38 MAPK).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Alzheimer's disease (AD) models were established using APP/presenilin-1 (APP/PS1) double-transgenic mice and N2a cells overexpressing the human Swedish mutant APP (N2a-APPswe). Immunofluorescence staining was employed to assess DOT1L expression and localization in mouse brain tissues. N2a-APPswe cells were treated with the DOT1L-specific inhibitor EPZ5676 and divided into four groups: blank control, solvent control, DOT1L inhibitor, and DOT1L inhibitor plus p38 agonist (&lt;i&gt;Gynostemma pentaphyllum&lt;/i&gt; extract). Western blotting was performed to measure the phosphorylation levels of DRP1 at Ser616 and Ser637, the levels of autophagy-related proteins p62 and the LC3-Ⅱ/LC3-Ⅰ ratio, the phosphorylation level of p38 MAPK, as well as the expression of APP and APP-processing proteins BACE1 and PS1. Reverse transcription quantitative polymerase chain reaction was used to detect mRNA levels of APP and genes involved in mitochondrial fission and fusion. Proteomics data were systematically analyzed through Gene Ontology analysis, WikiPathways enrichment analysis, and STRING protein-protein interaction network analysis to identify key signaling pathways. Mitochondrial network morphology was evaluated by Mito-Tracker fluorescence staining to measure average branch length.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;DOT1L expression was significantly reduced in neurons of APP/PS1 mice compared to wild-type controls. DOT1L inhibition led to decreased H3K79 dimethylation levels (&lt;i&gt;P&lt;/i&gt;&lt;0.01), accompanied by a marked increase in APP protein expression (&lt;i&gt;P&lt;/i&gt;&lt;0.01), although APP mRNA levels were reduced (&lt;i&gt;P&lt;/i&gt;&lt;0.01). Proteomics analysis revealed that differentially expressed proteins were highly enriched in the mitochondrial electron transport chain. Compared with the solvent control, the DOT1L inhibitor group showed inhibited mitochondrial fission, as evidenced by decreased p-DRP1 (Ser616), increased p-DRP1 (Ser637), downregulated &lt;i&gt;MIEF1&lt;/i&gt; mRNA, upregu-lated &lt;i&gt;MFN1&lt;/i&gt; mRNA (all &lt;i&gt;P&lt;/i&gt;&lt;0.05), and increased average mitochondrial branch length (&lt;i&gt;P&lt;/i&gt;&lt;0.05), along with reduced phosphorylation level of p38 MAPK (&lt;i&gt;P&lt;/i&gt;&lt;0.05). Co-administration of the p38 agonist significantly reversed these mitochondrial dynamics abnormalities (all &lt;i&gt;P&lt;/i&gt;&lt;0.05) and attenuated the abnormally elevated protein levels of APP, BACE1, and PS1 (all &lt;i&gt;P&lt;/i&gt;&lt;0.05) compared to the DOT1L inhibitor group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;DOT1L maintains normal mitochondrial fission and functional homeostasis through regulation of the p38 MA","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"391-403"},"PeriodicalIF":0.0,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148377275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Mechanism of Bushen Yijing Formula improving cognitive function in Alzheimer<b>'</b>s disease model mice].","authors":"Zhezuo Zhang, Deyu Li, Jing Liu, Lei Lu, Wenhui Cai, Guruan Yu","doi":"10.3724/zdxbyxb-2025-0747","DOIUrl":"10.3724/zdxbyxb-2025-0747","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To explore the mechanism of Bushen Yijing Formula (BSYJF) in the treatment of Alzheimer's disease (AD) through an integrated approach combining transcriptomics, network pharmacology, and molecular docking.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Twelve specific pathogen-free male C57BL/6 mice, aged 6 months, were used in this study. Among them, four wild-type mice served as the normal control group, and eight amyloid precursor protein (APP)/presenilin 1 (PS1) double-transgenic mice were randomly divided into a model control group and a BSYJF group, with four mice in each group. Mice in the BSYJF group were orally administered 8.56 mL/kg BSYJF by gavage once daily, while those in the model control and normal control groups received an equal volume of normal saline by gavage. All treatments were continued for 12 consecutive weeks. Cognitive function and hippocampal amyloid β-protein (Aβ) deposition were assessed using behavioral tests and immunohisto-chemistry. Mouse brain tissue samples were subjected to transcriptomic sequencing to identify differentially expressed genes (DEGs). Functional enrichment analyses were performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). In parallel, active compounds of BSYJF were screened via the TCMSP and PubChem databases, and AD-related targets were retrieved from GeneCards and other disease databases. Core targets were identified by intersecting these targets with transcriptomic DEGs. Molecular docking and molecular dynamics simulations were employed to evaluate binding affinity between active compounds and core targets, and quantitative polymerase chain reaction (qPCR) was used to validate expression changes of core target genes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;BSYJF treatment improved cognitive function and reduced hippocampal Aβ deposition in APP/PS1 mice. Transcriptomic analysis revealed 73 DEGs between the model and BSYJF groups. GO analysis identified enrichment in 281 biological processes, 104 cellular components, and 120 molecular functions. KEGG analysis highlighted 110 pathways, and GSEA supplemented 322 enriched gene sets, many related to the immune system, neurodegenerative diseases, and signaling pathways such as Th17 cell differentiation and NF-κB. Integrated analysis with network pharmacology prioritized 10 core targets. Molecular docking and molecular dynamics simulations indicated strong structural stability and binding affinity of BSYJF bioactive constituents to these core targets. qPCR results confirmed that BSYJF down-regulated the expression of &lt;i&gt;Aurkb&lt;/i&gt;, &lt;i&gt;Nr1i3&lt;/i&gt;, and &lt;i&gt;Ttk&lt;/i&gt;, while upregulating &lt;i&gt;Apob&lt;/i&gt; and &lt;i&gt;Ces1d&lt;/i&gt;, consistent with the transcriptomic findings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;BSYJF may regulate immune-inflammatory responses and alleviate neuronal damage through a multi-component, multi-target, and multi-pathway approach, thereby improving cognitive function i","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"437-448"},"PeriodicalIF":0.0,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Development and validation of a risk assessment model for interstitial lung disease in patients with rheumatoid arthritis].","authors":"Xiuyuan Xu, Dan Liang, Weiwei Ye, Mengru Guo, Jianwei Xiao, Rongsheng Wang, Dongyi He","doi":"10.3724/zdxbyxb-2025-0507","DOIUrl":"10.3724/zdxbyxb-2025-0507","url":null,"abstract":"<p><strong>Objectives: </strong>To develop and validate a risk assessment model for interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>A retrospective study analyzed clinical data from 312 patients with RA treated at Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between January 1, 2021 and June 30, 2024. Patients were divided into an RA-only group and an RA-ILD group based on the presence of ILD. Demographic characteristics, laboratory test results, clinical manifestations, disease activity scores, medication history, joint X-ray findings, and traditional Chinese medicine (TCM) syndrome types were collected as potential predictors. Variables were screened using univariable analysis and LASSO regression, and binary logistic regression was used to build the model and construct a nomogram using the rms package in R software. The discrimination and clinical utility of this model were assessed via receiver operating characteristic (ROC) and decision curves, and calibration was evaluated using Bootstrap-resampled (1000 iterations) calibration curves. A LightGBM machine learning model was also developed based on the selected predictors, and its performance was evaluated using ROC and precision-recall (PR) curves. Five-fold cross-validation was employed to further assess the robustness of the predictors.</p><p><strong>Results: </strong>Multivariate logistic regression identified sex, age, anti-cyclic citrullinated peptide (CCP) antibody, disease activity score in 28 joints (DAS28) based on erythrocyte sedimentation rate (ESR), Krebs von den Lungen-6 (KL-6), international normalized ratio (INR), activated partial thromboplastin time (APTT), and methotrexate use as independent predictors of RA-ILD (all <i>P</i><0.05). The model showed excellent discrimination with an area under the curve (AUC) of 0.976. Calibration curves showed strong agreement between predicted and observed probabilities, with an optimism-corrected slope approaching unity (0.9973). Decision curve analysis demonstrated a high net clinical benefit. The LightGBM model yielded an ROC AUC of 0.8464 and a PR AUC of 0.9417. In five-fold cross-validation, all ROC AUC values were greater than 0.65.</p><p><strong>Conclusions: </strong>The developed risk assessment model for ILD in patients with RA indicates high predictive ability and clinical utility.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"294-302"},"PeriodicalIF":0.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Gut-brain-joint axis in rheumatoid arthritis: from microeco-logical disturbance to multi-target synergy].","authors":"Shenlong Yi, Qiwang He, Yanan Li, Bijiang Wan","doi":"10.3724/zdxbyxb-2025-0569","DOIUrl":"10.3724/zdxbyxb-2025-0569","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and bone destruction, accompanied by gut microbiota dysbiosis, neuroimmune dysfunction, and systemic inflammatory amplification. Increasing evidence from the gut-joint axis indicates that microbial dysbiosis disrupts intestinal barrier integrity, enhances permeability, and promotes the translocation of microbial products and antigens, thereby triggering systemic inflammation and autoimmune responses. Meanwhile, alterations in microbial metabolites, including short-chain fatty acids, bile acids, and tryptophan derivatives, drive disease progression by regulating mucosal homeostasis, inflammatory resolution, and the Th17 cells/Tr cells balance. Persistent dysbiosis further activates peripheral immunity and promotes the recruitment of pro-inflammatory cells and mediators to the synovium, resulting in synovial hyperplasia, cartilage degradation, and bone erosion. Concurrently, gut-derived metabolic signals, vagal afferents, and immune mediators modulate central nervous system function and neuroinflammation, whereas brain-derived stress responses regulate intestinal barrier function, microbial composition, and gut immune homeostasis via the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system, collectively exacerbating systemic inflammation. Thus, a dynamic cross-system network linking the gut, brain, and joints is established, involving neural pathway coupling, immune cell migration and recruitment, endocrine regulation, and metabolic messenger- and inflammatory axis-mediated interactions. Microbiota-directed strategies restore microbial homeostasis and barrier integrity to reduce the initiation of inflammation; metabolic interventions rebalance immune and bone homeostasis through key signaling pathways, e.g., tryptophan and short-chain fatty acid pathways; neuroimmune regulation attenuates inflammatory amplification via the cholinergic anti-inflammatory pathway and HPA axis modulation; and multi-target approaches integrate the advantages of microbiota, metabolism, neural, and local inflammatory control to improve therapeutic efficacy. This review elucidates RA from the integrated perspective of the gut-brain-joint axis, providing mechanistic insights into systemic inflammation and supporting the development of novel therapeutic strategies.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"338-351"},"PeriodicalIF":0.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Research progress on the application of telitacicept in rheumatism and autoimmune diseases].","authors":"Xue Wang, Yihuai Xu, Guixia Tong, Hongxia Zhang","doi":"10.3724/zdxbyxb-2025-0587","DOIUrl":"10.3724/zdxbyxb-2025-0587","url":null,"abstract":"<p><p>Traditional treatment regimens for rheumatism and autoimmune diseases are associated with significant adverse effects, and some patients have a limited response, leading to poor prognosis. Telitacicept, a biologic agent and fusion protein targeting B cell activating factor (BAFF) and a proliferation inducing ligand (APRIL), offers a novel therapeutic strategy for refractory rheumatism and autoimmune diseases. Clinical trials have shown promising efficacy and safety. In systemic lupus erythematosus, telitacicept reduces disease activity and facilitates glucocorticoid sparing, with favorable outcomes also observed in pediatric patients. In Sjögren's syndrome, telitacicept achieves sustained improvement in clinical symptoms and disease activity. In rheumatoid arthritis, telitacicept improves the response rates for the American College of Rheumatology 20% improvement criteria (ACR20) and for the American College of Rheumatology 50% improvement criteria (ACR50) while significantly reducing glucocorticoid requirements. In IgA vasculitis, studies focused on patients with renal involvement, and showed efficacy in reducing proteinuria in both adults and children. In myasthenia gravis, telitacicept reduces disease severity and improves quality of life. Additionally, telitacicept has shown preliminary therapeutic potential in IgG4-related disease and granulomatosis with polyangiitis, warranting further investigation. Existing clinical data indicate a favorable overall safety profile for telitacicept. However, attention should be paid to long-term risks of infection, decreased immunoglobulin levels, potential resistance mechanisms, and its efficacy and safety in special populations. This review summarizes recent research progress on the use of telitacicept in rheumatism and autoimmune diseases, aiming to provide a reference for its clinical application.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"364-372"},"PeriodicalIF":0.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Endogenous neddylation in B cells regulates immune responses in mice].","authors":"Xin Jin, Luyao Zhu, Lizhi Zhang, Tianhang Chen, Mingqian Zhou","doi":"10.3724/zdxbyxb-2025-0646","DOIUrl":"10.3724/zdxbyxb-2025-0646","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the regulatory role of endogenous neddylation in B cell-mediated immune responses.</p><p><strong>Methods: </strong>B cell-specific <i>Ube2m</i> knockout mice (<i>CD19^cre</i>^/<i>⁺Ube2m^fl</i>^/<i>^fl</i>) were generated using the Cre-LoxP system, with littermate <i>Ube2m^fl</i>^/<i>^fl</i>mice serving as normal controls. Mice were immunized with thymus-independent antigens 4-hydroxy-3-nitrophenylacetyl (NP)-lipopoly saccharide (LPS) and 2,4-dinitrophenyl (DNP)-Ficoll, as well as thymus-dependent antigens NP-chicken gamma globulin (CGG) and DNP-keyhole limpet hemocyanin (KLH). Serum levels of specific antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to determine the proportions of splenic germinal center B cells, splenic plasma cells, and bone marrow plasma cells in mice immunized with NP-LPS or NP-CGG. Statistical analyses were performed to assess differences in immune responses among the groups.</p><p><strong>Results: </strong>Compared with controls, <i>Ube2m</i>-deficient mice showed significantly lower levels of anti-NP immunoglobulin (Ig)G2a, IgG2b, IgG2c, and IgG3 after NP-LPS immunization, and reduced levels of all anti-DNP IgG subclasses after DNP-Ficoll immunization (all <i>P</i><0.05), with no significant change in IgM levels. The proportions of total splenic germinal center B cells, total bone marrow plasma cells, and NP-specific plasma cells were also significantly decreased after NP-LPS immunization (all <i>P</i><0.01). Following immunization with NP-CGG or DNP-KLH, <i>Ube2m</i> knockout mice exhibited reduced levels of anti-NP or anti-DNP IgM and all IgG subclasses (all <i>P</i><0.05), with antigen-dependent differences in the timing and extent of antibody reduction. After NP-CGG immunization, the proportions of total splenic plasma cells, NP-specific plasma cells, and NP-specific germinal center B cells were markedly decreased (all <i>P</i><0.01).</p><p><strong>Conclusions: </strong>Endogenous neddylation deficiency in B cells broadly impairs immune responses to both thymus-independent and thymus-dependent antigens in mice, and its regulatory effects are antigen-dependent.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"321-331"},"PeriodicalIF":0.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Advances in the clinical management of acute severe ulcerative colitis].","authors":"Wenyi Shao, Ying Zhou, Feng Xu","doi":"10.3724/zdxbyxb-2025-0382","DOIUrl":"10.3724/zdxbyxb-2025-0382","url":null,"abstract":"<p><p>Acute severe ulcerative colitis (ASUC) is a critical emergency life-threatening complication of inflammatory bowel disease. A subset of patients fails to respond to first-line intravenous corticosteroid therapy and requires timely salvage treatment. Previously, guidelines recommended infliximab and cyclosporine as the main salvage therapies; however, recent years have witnessed clinical advances. Accelerated and intensified dosing regimens of infliximab, compared with standard dosing, may help patients with high inflammatory burden and hypoalbuminemia achieve earlier clinical and biochemical remission. Among small molecule Janus kinase inhibitors, tofacitinib as an adjunct to intravenous corticosteroids has been shown to improve short-term clinical response rates, while upadacitinib has shown promising efficacy as a salvage therapy when intravenous corticosteroids, standard or intensified infliximab are ineffective. For patients unresponsive to monotherapy or those with extraintestinal manifestations, dual-targeted therapy, through multi-pathway synergistic blockade, achieves superior clinical, endoscopic, and biochemical outcomes compared to monotherapy, providing new evidence-based support for treatment optimization. In addition, exclusive enteral nutrition and hyperbaric oxygen therapy play important roles in the comprehensive management of ASUC by modulating the gut microbiota and promoting mucosal healing, respectively. This review summarizes the therapeutic outcomes and limitations of these emerging pharmacological agents or regimens in the clinical treatment of ASUC, aiming to provide a reference for optimizing clinical management strategies for ASUC.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"373-380"},"PeriodicalIF":0.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}