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摘要： Inflammatory skin diseases (ISDs) exhibit varying prevalence across different ancestry background and geographical regions. Genetic research for complex ISDs has predominantly centered on European Ancestry (EurA) populations and genetic effects on immune cell responses but generally failed to consider contributions from other cell types in skin. Here, we utilized 273 genetic signals from seven different ISDs: acne, alopecia areata (AA), atopic dermatitis (AD), psoriasis, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and vitiligo, to demonstrate enriched IL1 signaling in keratinocytes, particularly in signals with higher risk allele frequencies in the African ancestry. Using a combination of ATAC-seq, Bru-seq, and promoter capture Hi-C, we revealed potential regulatory mechanisms of the acne locus on chromosome 2q13. We further demonstrated differential responses in keratinocytes upon IL1β stimulation, including the pro-inflammatory mediators CCL5, IL36G, and CXCL8. Taken together, our findings highlight IL1 signaling in epidermal keratinocytes as a contributor to ancestry-related differences in ISDs. : ISD-associated loci highlight IL-1 signaling enrichment in African ancestry. Multi-omics reveals regulatory mechanisms at 2q13 for acne.

关键词： endometrial carcinoma   prognosis   immunohistochemistry   anti-tumor immunity   qPCR  

摘要： Introduction Endometrial Carcinoma (UCEC) is a prevalent malignant tumor within the female reproductive system. HLA-DMB, the beta chain of the non-classical MHC class II protein HLA-DM, has been implicated in the progression of various cancers. However, its role in the development of endometrial carcinoma remains unclear. Therefore, we conducted a preliminary exploration of the prognostic value and potential mechanisms of HLA-DMB in uterine corpus endometrial carcinoma (UCEC).Methods The differential expression of HLA-DMB was analyzed in 554 tumor samples and 35 normal samples obtained from the TCGA database. The differential expression of HLA-DMB across various cancers, along with immune infiltration analysis, was conducted using the TIMER2.0 database. Additionally, the expression of HLA-DMB in endometrial carcinoma was examined in the GEPIA2 database, along with its relationship to prognosis. Furthermore, TISIDB was utilized to predict the relationships between HLA-DMB and various immune enhancement factors as well as immunosuppressive factors. Gene Ontology (GO) analysis and Gene Set Enrichment Analysis (GSEA) were employed to explore the signaling pathways associated with HLA-DMB in endometrial cancer. Univariate COX regression analysis was performed to identify prognostic factors for endometrial carcinoma (EC), and a multivariate COX proportional hazards regression model was used to confirm that HLA-DMB can serve as an independent prognostic factor for EC. The protein interaction network of HLA-DMB was constructed using the STRING database, and the chemical drugs related to HLA-DMB were predicted through the CTD database. Finally, the expression of HLA-DMB was validated by qPCR and *** The expression of HLA-DMB at both mRNA and protein levels is significantly higher in UCEC tissues compared to normal tissues. Prognostic analyses indicate that increased expression of HLA-DMB correlates with improved patient prognosis, suggesting its pote

关键词： 丙型肝炎病毒   单克隆抗体   噬菌体展示   抗体库   多肽表位   酶联免疫吸附试验   灵敏度   特异性  

摘要： [目的]旨在筛选并制备出体外诊断试剂用人源丙型肝炎病毒(HCV)特异性单克隆抗体。[方法]从感染丙型肝炎病毒的患者全血中提取总RNA,构建噬菌体文库;通过噬菌体展示技术筛选抗HCV核心抗原抗体,阳性克隆经测序后构建全人源抗体,最后对人源HCV单克隆抗体进行纯化制备及双抗体夹心法检测性能评估。[结果]通过噬菌体展示技术成功筛选出4株针对HCV核心抗原的单克隆抗体;其中优选45#、91#抗体配对检测50份阴性血清样本和50份阳性血清样本,检测灵敏度为96%,特异性为98%。[结论]通过噬菌体展示技术成功获得4株人源丙型肝炎病毒单克隆抗体,在HCV抗原的检测中具有应用的潜力,为丙肝抗原诊断试剂盒原材料的开发奠定了基础。

关键词： cartilage degeneration   interleukin-6 receptor   JAK2 signaling   osteoarthritis   senescent cells  

摘要： Osteoarthritis (OA) is an age-related degenerative joint disease, prominently influenced by the pro-inflammatory cytokine interleukin-6 (IL-6). Although elevated IL-6 levels in joint fluid are well-documented, the uneven cartilage degeneration observed in knee OA patients suggests additional underlying mechanisms. This study investigates the role of interleukin-6 receptor (IL-6R) in mediating IL-6 signaling and its contribution to OA progression. Here, significantly elevated IL-6R expression is identified in degenerated cartilage of OA patients. Further, in vivo experiments reveal that intra-articular injection of recombinant IL-6R protein or activation of gp130 (Y757F mutation) accelerates OA progression. Conversely, knockout of IL-6R or JAK2, as well as treatment with a JAK inhibitor, alleviates OA symptoms. Mechanistically, chondrocytes derived from degenerative cartilage exhibit impaired nuclear localization of SOX9, a key regulator of cartilage homeostasis. JAK inhibition stabilizes SIRT1, reduces SOX9 acetylation, and thereby facilitates SOX9 nuclear localization, promoting cartilage repair. Additionally, the JAK inhibitor-induced apoptosis in p21-positive senescent cells, and their targeted clearance successfully alleviates OA in p21-3MR mice. In conclusion, these findings reveal a novel mechanism by which inhibiting the IL-6R/JAK2 pathway can alleviate OA. Furthermore, this study proposes targeting p21-positive senescent cells as a new therapeutic strategy for OA.

关键词： 慢性乙型肝炎   乙肝病毒载量   肝功能   肝纤维化   T淋巴细胞亚群  

摘要： 目的 分析慢性乙型肝炎（CHB）患者乙肝病毒（HBV）-DNA载量与其肝功能、肝纤维化程度和T淋巴细胞亚群水平,并分析各指标的相关性。方法 选取2023年4月-2024年4月于山东公共卫生临床中心收治的122例C HB患者为研究对象,根据HBV-DNA载量分为高载量组（n=48,HBV-DNA载量≥10～5 copies/ml）和低载量组（n=74,HBV-DNA载量<10～5 copies/ml）。检测血清HBV-DNA载量、血清谷草转氨酶（AST）、谷丙转氨酶（ALT）、总胆红素（TBIL）、透明质酸（HA）、层黏连蛋白（LN）、Ⅲ型前胶原（PCⅢ）和Ⅳ型胶原（CⅣ）水平。结果 高载量组CHB患者ALT、AST和TBILL分别为（113.84±11.63）、（95.65±9.78）和（60.24±7.37）U/L.均高于低载量组（P<0.05）。高载量组CHB患者HA、LN、PCⅢ和CⅣ分别为（436.21±41.52）、（244.85±31.48）、（314.39±28.71）和（85.31±20.92） ng/ml均高于低载量组（P<0.05）。高载量组CD3+、CD4+和CD4+/CD8+低于低载量组（P<0.05）,CD8+高于低载量组（P=0.001）。CHB患者ALT、AST、TBIL、HA、LN、PCⅢ、CⅣ和CD8+水平均与HBV-DNA载量呈正相关（r=0.522、0.513、0.494、0.421、0.456、0.503、0.418、0.311,P均<0.05）,CD3+、CD4+和CD4+/CD8+水平与HBV-DNA载量呈负相关（r=-0.346、-0.454、-0.492,P均<0.001）。结论 CHB患者HBV-DNA载量越高,可能与患者肝功能越差、肝纤维化程度重和免疫功能低有关。

关键词： 瓜蒌红花甘草汤   带状疱疹病毒感染   炎症   免疫   疼痛介质  

摘要： 目的 探讨瓜蒌红花甘草汤对带状疱疹病毒感染患者中医症候、T淋巴细胞亚群及微炎症状态的影响,并评估治疗安全性。方法 选取黑龙江中医药大学附属第一医院2020年12月-2023年12月收治的120例带状疱疹病毒感染患者,分为常规组（阿昔洛韦治疗）和联合组（阿昔洛韦+瓜蒌红花甘草汤治疗）,各60例,两组均治疗2周。比较两组治疗2周后的临床疗效,症状控制时间,治疗前和治疗2周后的证候积分、T淋巴细胞亚群水平、疼痛介质及微炎症状态,治疗期间不良反应情况。结果 治疗2周后,联合组疗效优于常规组（P=0.028）。治疗2周后,两组主、次证评分、中医证候总分、CD8+、血清环氧化酶-2（COX-2）、C-反应蛋白（CRP）水平均降低,且联合组以上指标分别为（6.01±0.66）分、（3.96±0.41）分、（9.97±1.01）分、（25.26±3.02）%、（22.16±2.36）ng/ml、（8.62±0.87） mg/L,较常规组更低（P<0.05）;CD3+、CD4+、CD4+/CD8+、血清β-内啡肽（β-EP）、白细胞介素（IL）-2水平在两组治疗2周后升高,且联合组以上指标分别为（68.29±6.56）%、（43.03±4.42）%、1.70±0.26、（129.93±13.02）μg/L、（13.96±1.40）pg/ml,高于常规组（P<0.05）。联合组止痛、止疱、结痂及脱痂时间均短于常规组（P<0.05）。两组治疗期间的不良反应发生率差异无统计学意义（P=0.509）。结论 瓜蒌红花甘草汤治疗带状疱疹病毒感染能有效地改善患者免疫功能,缓解疼痛介质及微炎症状态指标,进而有利于控制临床症状和提高临床疗效,且安全性良好。

关键词： Acute Pancreatitis (AP)   C-Reactive protein (CRP)   Procalcitonin (PCT)   Interleukin-6 (IL-6)   Neutrophil-to-lymphocyte ratio (NLR)   Triglyceride-glucose index (TyG Index)  

摘要： To evaluate the clinical utility of PCT, CRP, IL-6, NLR, and TyG index in improving the early diagnosis and severity assessment of acute pancreatitis (AP). This retrospective study included 137 AP patients and 30 healthy controls from Hunan Provincial People's Hospital (January 2021-September 2023). Univariate and multivariate logistic regression analyses assessed the associations between biomarkers and severe acute pancreatitis (SAP). Receiver operating characteristic (ROC) curves, DeLong test, and Bonferroni correction were used to evaluate predictive performance. Model robustness was validated via 5-fold cross-validation. PCT, CRP, IL-6, NLR, and TyG index levels were significantly elevated in AP patients compared to controls (P < 0.001) and correlated with disease severity (P < 0.05). CRP and NLR levels differed significantly among mild, moderate, and severe AP (P < 0.01). Alcohol consumption and hyperlipidemia were significantly linked to AP severity (P for trend < 0.0001). Multivariate analysis identified hyperlipidemia (OR = 3.030, P = 0.040), CRP (OR = 1.011, P < 0.001), and NLR (OR = 1.078, P = 0.020) as independent SAP predictors. The combined model of CRP + NLR + TyG achieved the highest AUC (0.882, sensitivity = 77.2%, specificity = 88.5%), though it was not significantly better than CRP + NLR or CRP + TyG models (P > 0.05). 5-fold cross-validation confirmed consistent performance (mean AUC = 0.817 +/- 0.118). PCT, CRP, IL-6, NLR, and TyG index are valuable in diagnosing and assessing AP prognosis. Hyperlipidemia, CRP, and NLR are reliable independent predictors of SAP. Combining multiple biomarkers enhances diagnostic precision and provides guidance for personalized treatment strategies in AP.

关键词： Anti-TNF   antibody formation   inflammatory bowel disease   loss of response   Saudi Arabia  

摘要： Background: The emergence of tumor necrosis factor inhibitors (anti-TNF) has considerably changed the management of inflammatory bowel disease (IBD) in patients who do not respond to traditional therapies. This study assesses the prevalence of anti-TNF drug levels (DLs) and antibodies (ATAbs) in patients with IBD in Saudi Arabia and explores their associations with IBD type and prior anti-TNF failure. Methods: This cross-sectional study included patients aged 14-75 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC), treated with anti-TNF medications at King Fahad Medical City over January 2016 to December 2022. Data were analyzed using descriptive statistics, Mann-Whitney U test, Kruskal-Wallis test, Pearson's Chi-squared test, and multinomial logistic regression. Results: Among 392 patients with IBD (median age, 31 years), 75.8% were diagnosed with CD and 24.2% with UC. Anti-TNF levels were subtherapeutic in 27.0% patients, therapeutic in 21.5%, and supratherapeutic in 51.5%. ATAbs were negative in 73.1% patients, weakly positive in 9.8%, and positive in 17.1%. Subtherapeutic anti-TNF levels were significantly associated with positive ATAbs (P < 0.001). Prior anti-TNF therapy failure was observed in 37.2% cases, with 15.3% showing immunogenicity. No significant demographic differences were noted across ATAbs groups. Conclusion: We highlight the prevalence of subtherapeutic and supratherapeutic anti-TNF levels among patients with IBD in Saudi Arabia and their association with ATAbs. The findings underscore the importance of monitoring anti-TNF DLs and ATAbs to optimize treatment outcomes in IBD management. Future research should focus on the longitudinal impact of these factors and explore genetic predictors of treatment response.

关键词： Interleukin-1   collagen VII   cytokines   fibrosis   pseudosyndactyly