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

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[Development and validation of a risk assessment model for interstitial lung disease in patients with rheumatoid arthritis]. [类风湿关节炎患者间质性肺病风险预测模型的建立和验证]。
Xiuyuan Xu, Dan Liang, Weiwei Ye, Mengru Guo, Jianwei Xiao, Rongsheng Wang, Dongyi He
{"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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Gut-brain-joint axis in rheumatoid arthritis: from microeco-logical disturbance to multi-target synergy]. [基于肠脑关节轴的类风湿关节炎干预策略:从微生态干扰到多靶点协同]。
Shenlong Yi, Qiwang He, Yanan Li, Bijiang Wan
{"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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Research progress on the application of telitacicept in rheumatism and autoimmune diseases]. 泰利他塞普在风湿性免疫疾病中的应用研究进展
Xue Wang, Yihuai Xu, Guixia Tong, Hongxia Zhang
{"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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Endogenous neddylation in B cells regulates immune responses in mice]. [小鼠B细胞内源性伪泛素化调节免疫反应]。
Xin Jin, Luyao Zhu, Lizhi Zhang, Tianhang Chen, Mingqian Zhou
{"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<sup>cre</sup></i><sup>/</sup><i><sup>+</sup>Ube2m<sup>fl</sup></i><sup>/</sup><i><sup>fl</sup></i>) were generated using the Cre-LoxP system, with littermate <i>Ube2m<sup>fl</sup></i><sup>/</sup><i><sup>fl</sup></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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Haploinsufficiency of A20 in a family caused by a heterozygous deletion in the TNFAIP3 gene]. [一个家族中由TNFAIP3基因杂合缺失引起的A20单倍不足]。
Cuili Yi, Jihong Xiao
{"title":"[Haploinsufficiency of A20 in a family caused by a heterozygous deletion in the <i>TNFAIP3</i> gene].","authors":"Cuili Yi, Jihong Xiao","doi":"10.3724/zdxbyxb-2025-0545","DOIUrl":"10.3724/zdxbyxb-2025-0545","url":null,"abstract":"<p><p>The proband was a 3-year-4-month-old boy who had experienced recurrent diarrhea, fever, joint swelling and pain for more than a year accompanied by oral and perianal ulcers. Gastrointestinal endoscopy revealed multiple colorectal ulcers. The proband's 36-year-old father had a three-year history of oral ulcers and a one-year history of recurrent diarrhea; gastroscopy showed chronic non-atrophic gastritis with erosion and duodenitis, while colonoscopy was unremarkable. Whole exome sequencing revealed that the proband and his parents had no pathogenic single nucleotide variants or small insertions/deletions. Subsequent copy number variation analysis identified a heterozygous deletion of exons 2-9 in the tumor necrosis factor-α-induced protein 3 (TNFAIP3) gene in both the proband and his father, which was confirmed by quantitative PCR. Based on the clinical manifestations and genetic findings, the proband and his father were diagnosed with haploinsufficiency of A20 (HA20). Therefore, in patients with suspected HA20 presenting early-onset Behçet's syndrome-like manifestations, copy number variation analysis should be performed when whole exome sequencing fails to detect single nucleotide variants or small insertions/deletions in the <i>TNFAIP3</i> gene.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"332-337"},"PeriodicalIF":0.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Advances in the clinical management of acute severe ulcerative colitis]. 急性重度溃疡性结肠炎的临床治疗进展
Wenyi Shao, Ying Zhou, Feng Xu
{"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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Clinical characteristics and outcomes of children with rheu-matoid factor-positive polyarticular juvenile idiopathic arthritis]. [类风湿因子阳性儿童多关节幼年特发性关节炎的临床特点及结局分析]。
Yue Zhou, Jianqiang Wu, Meiping Lu
{"title":"[Clinical characteristics and outcomes of children with rheu-matoid factor-positive polyarticular juvenile idiopathic arthritis].","authors":"Yue Zhou, Jianqiang Wu, Meiping Lu","doi":"10.3724/zdxbyxb-2025-0574","DOIUrl":"10.3724/zdxbyxb-2025-0574","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To compare the clinical characteristics and outcomes between patients with rheumatoid factor (RF)-positive and RF-negative polyarticular juvenile idiopathic arthritis (pJIA).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A retrospective analysis was conducted on clinical data of 131 children diagnosed with pJIA at the Children's Hospital, Zhejiang University School of Medicine from January 2019 to January 2025. Patients were divided into an RF-positive group (&lt;i&gt;n&lt;/i&gt;=59) and an RF-negative group (&lt;i&gt;n&lt;/i&gt;=72) based on serum RF status. Disease activity was assessed using the Juvenile Arthritis Disease Activity Score-27 (JADAS-27). All patients were followed for at least 6 months, with a maximum follow-up duration of 6 years. Clinical features, laboratory findings, and outcomes were compared between the two groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among the 131 pJIA patients, 122 (93.1%) had high disease activity at baseline. Compared with the RF-negative group, the RF-positive group had a higher proportion of females (58.3% &lt;i&gt;vs&lt;/i&gt;. 84.7%, &lt;i&gt;P&lt;/i&gt;&lt;0.01), an older age at onset (7.14±3.98 years &lt;i&gt;vs&lt;/i&gt;. 8.86±4.02 years, &lt;i&gt;P&lt;/i&gt;&lt;0.05), and a higher prevalence of interstitial lung disease (4.2% &lt;i&gt;vs&lt;/i&gt;. 23.7%, &lt;i&gt;P&lt;/i&gt;&lt;0.01). The most frequently affected joints were the wrist in the RF-positive group, and the knee joints in the RF-negative group. At baseline, serum levels of IL-2, IL-6, IL-10, and tumor necrosis factor-α were significantly higher in the RF-positive group than those in the RF-negative group (all &lt;i&gt;P&lt;/i&gt;&lt;0.05). A total of 101 patients (77.1%) received biologic-targeted therapies, 46 (78.0%) in RF-positive group, and 55 (76.4%) in RF-negative group. Among them, 23 RF-positive patients (50.0%) and 12 RF-negative patients (21.8%) required two or more biologic-targeted drugs. RF positivity was identified as an independent risk factor for the use of two or more biologic-targeted drugs (OR=3.232, 95%CI: 1.109-9.421, &lt;i&gt;P&lt;/i&gt;&lt;0.05). Both groups showed significant reductions in JADAS-27 scores at 3, 6, 12, 24, 36, 48, 60, 72 months after treatment initiation compared with baseline (all &lt;i&gt;P&lt;/i&gt;&lt;0.01), with no significant differences in JADAS-27 scores or remission rates between the two groups at any follow-up time point (all &lt;i&gt;P&lt;/i&gt;&gt;0.05). The median time to achieve first clinical remission after treatment was 24 months in both groups (&lt;i&gt;P&lt;/i&gt;&gt;0.05). No significant differences were observed in remission rates or the proportion of patients requiring two or more biologic-targeted drugs among different types of biologic-targeted drugs (all &lt;i&gt;P&lt;/i&gt;&gt;0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Children with RF-positive pJIA showed higher baseline inflammatory status and a higher incidence of pulmonary involvement, yet they achieved comparable remission rates to those with RF-negative pJIA. Biologic-targeted therapies may contribute to improved remission rates and outcomes, but RF-positive patients may require switching or","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"285-293"},"PeriodicalIF":0.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Research progress of the ULBP-NKG2D axis in autoimmune diseases]. ULBPs-NKG2D轴在自身免疫性疾病中的研究进展
Jiani Ma, Jing Wu, Yanliang Jin
{"title":"[Research progress of the ULBP-NKG2D axis in autoimmune diseases].","authors":"Jiani Ma, Jing Wu, Yanliang Jin","doi":"10.3724/zdxbyxb-2025-0692","DOIUrl":"10.3724/zdxbyxb-2025-0692","url":null,"abstract":"<p><p>The activating receptor natural killer group 2 member D (NKG2D) and its ligands, the UL16-binding protein (ULBP), play pivotal roles in autoimmune diseases, characterized by multidimensional regulatory features. This review employs a three-dimensional framework of \"ligand supply-ligand fate-receptor regulation\" to analyze the research progress of the ULBP-NKG2D axis in autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, multiple sclerosis, and Crohn disease. In systemic lupus erythematosus, the axis involves both peripheral immune suppression (driven by receptor internalization) and local tissue immune attack, collectively shaping the complex pathology. In rheumatoid arthritis, the core pathological dysre-gulation of the axis is concentrated in the inflammatory synovial microenvironment: membrane-bound ligands derived from synovial fibroblasts directly drive the cytotoxicity of local effector cells, exacerbating joint inflammatory damage, while these ligands may be cleaved by a disintegrin and metalloprotease 10 (ADAM10) into soluble forms that enter the circulation and mediate peripheral immunosuppression. In type 1 diabetes, pancreatic β cells directly trigger NKG2D-mediated immune killing by upregulating membrane-bound ULBP proteins. In multiple sclerosis, astrocyte-derived ULBP4, in both membrane-bound and soluble forms, enhances the migration and pro-inflammatory capacity of effector cells. In Crohn disease, endoplasmic reticulum stress induces widespread ULBP expression in intestinal epithelial and endothelial cells, collectively mediating immune cell recruitment and amplifying local inflammation. This review also summarizes the current status of innovative drugs targeting the NKG2D receptor and their clinical translation progress, aiming to provide a reference for unraveling the complex immunopathology and developing precision immunotherapy strategies.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"352-363"},"PeriodicalIF":0.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Association of metabolic syndrome and its components with gout: an analysis based on a large-scale health survey database]. [代谢综合征及其成分与痛风的关系:基于大型健康调查数据库的分析]。
Jianbin Li, Wei Liu
{"title":"[Association of metabolic syndrome and its components with gout: an analysis based on a large-scale health survey database].","authors":"Jianbin Li, Wei Liu","doi":"10.3724/zdxbyxb-2025-0660","DOIUrl":"10.3724/zdxbyxb-2025-0660","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the association of metabolic syndrome (MetS) and its components with gout.</p><p><strong>Methods: </strong>This study utilized data from 28 130 adults aged ≥18 years in the National Health and Nutrition Examination Survey (NHANES) 2007-2018, among whom 1279 were identified as gout patients. Logistic regression was used to assess the associations of MetS and its components with gout. Restricted cubic spline (RCS) models were employed to examine non-linear dose-response relationships between metabolic indicators and gout. Subgroup analyses were performed by age, sex, and body mass index (BMI), with interaction effects evaluated using the Wald test by including multiplicative interaction terms in the logistic regression models.</p><p><strong>Results: </strong>The prevalence of MetS was substantially higher in individuals with gout than in those without (66.9% <i>vs</i>. 33.3%). After adjusting for age, sex, BMI, smoking, and alcohol consumption, MetS was independently associated with gout (OR=2.55, 95%CI: 1.55-4.20, <i>P</i><0.01), with central obesity (OR=2.44, 95%CI: 1.55-3.85, <i>P</i><0.01) and hypertension (OR=1.70, 95%CI: 1.04-2.78, <i>P</i><0.05) showing the strongest associations. RCS analysis revealed J-shaped associations for BMI and fasting glucose, accelerating positive associations for waist circumference, mean systolic blood pressure, and triglyceride levels, and U-shaped associations for mean diastolic blood pressure and low-density lipoprotein cholesterol (LDL-C) levels (all <i>P</i><0.05). High-density lipoprotein cholesterol (HDL-C) showed a significant non-linear association, with the OR value of gout generally decreasing as HDL-C levels increased (<i>P</i><0.05). Subgroup analyses indicated that the association of MetS with gout was significantly stronger in females than that in males (OR: 5.07 <i>vs.</i> 2.34, interaction <i>P</i><0.05), and the association of diabetes with gout was more pronounced in those aged ≥50 years (OR=4.58) and in non-obese individuals (OR=5.21) (both interaction <i>P</i><0.01).</p><p><strong>Conclusions: </strong>MetS is independently associated with gout, exhibiting significant non-linear dose-response characteristics and population heterogeneity.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"311-320"},"PeriodicalIF":0.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Expression of Notch signaling pathway in children with Henoch-Schönlein purpura and its correlation with inflam-matory cytokines]. [Henoch-Schönlein紫癜患儿Notch信号通路的表达及其与炎症因子的相关性]。
Huishan Chen, Feng Li, Ying Tang, Ping Zeng
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