[摘 要] 目的：基于加权基因共表达网络分析（WGCNA）探讨贝沙罗汀治疗双打击淋巴瘤（DHL）的分子机制，为DHL治疗提供潜在靶点和实验依据。方法：从基因表达综合数据库（GEO）下载GSE44164和GSE43677表达谱数据集，筛选出差异表达基因（DEG）。采用WGCNA识别与DHL相关的基因模块，构建蛋白质相互作用（PPI）网络以筛选关键基因。通过药物预测平台EpiMed进行关联分析以确定DHL的潜在靶向治疗药物。利用CCK-8法和WB法检测贝沙罗汀对DHL细胞增殖及关键蛋白表达的影响，通过流式细胞术评估贝沙罗汀诱导细胞凋亡的效果。结果：WGCNA识别出与DHL高度相关的碧绿色模块，在PPI网络中筛选出10个枢纽基因，包括COL1A2、COL3A1、MMP2、COL5A2、DCN、BGN、FN1、MMP9、FBN1和LUM。药物关联分析确定贝沙罗汀为潜在治疗药物。体外实验显示，贝沙罗汀显著抑制U2932细胞活力（P < 0.05）、促进细胞凋亡（P < 0.001）、下调细胞中c-Myc和COL1A2的表达（均P < 0.05）。结论：贝沙罗汀可能通过抑制c-Myc信号通路及调控细胞外基质相关基因发挥抗DHL作用，其体内疗效及联合治疗潜力需进一步验证。

Objective : To study the differential expression and diagnostic value of miR-26a-5p and miR-151a-3p in plasma exosomes of tuberculosis. Methods : Differentially expressed miRNAs ( miR-26a-5p and miR-151a-3p) in tuberculosis exosomes were identified through bioinformatics website．Furthermore，70 tuberculosis patients (tuber- culosis group) and 58 healthy subjects ( healthy control group) were selected for clinical validation : Plasma exo- somes，extracted by differential centrifugation，were identified by Western blot，transmission electron microscopy， nanoparticle tracking analysis．The expression levels of miR-26a-5p and miR-151a-3p in plasma exosome were de- tected by RT-qPCR in the tuberculosis group and the control group．The diagnostic value of miR-26a-5p and miR- 151a-3p in tuberculosis was evaluated by ROC curve. Results : The characteristics of exosomes were identified by transmission electron microscopy，nanoparticle tracking analysis and Western blot，which showed that plasma exo- somes were extracted successfully．In clinical validation，the internal and external parameters were calibrated sim- ultaneously，the expression level of miR-26a-5p in plasma exosome of patients with tuberculosis was lower than that in control group (P＜0. 000 1) ，and the expression level of miR-151a-3p in plasma exosome of patients with tuber- culosis was higher than that in control group (P＜0. 000 1) ，which were consistent with the bioinformatics results. As a diagnostic marker，taking internal reference as the benchmark，the AUC of plasma exosome miR-26a-5p and miR-151a-3p for tuberculosis differentiation was 0. 872 and 0. 709，the AUC of the combined miR-26a-5p and miR- 151a-3p was 0. 915 (P ＜0. 000 1 ) ． Taking external reference as the benchmark ，the AUC of plasma exosomes miR-26a-5p and miR-151a-3p were 0. 829 and 0. 854 respectively ，the AUC of the combined miR-26a-5p and miR-151a-3p was 0. 911 (P＜0. 000 1) ． Conclusion The expression level of plasma exosome-derived miR-26a- 5p decreases in tuberculosis patients and the expression levelof miR-151a-3p increases，and the clinical diagnostic efficiency of bothis high，which may be a potential biomarker for the diagnosis of tuberculosis.

[摘 要] 目的：采用生物信息学方法分析E3泛素连接酶（HECW2）在胃腺癌组织中的表达及其临床意义，为寻找胃腺癌诊断和预后生物标志物提供新的线索。方法：用R语言分析HECW2在泛癌中的表达及其与泛癌预后的关系。借助UCSC Xena、HPA、Kaplan-Meier Plotter等数据库分析HECW2在胃腺癌组织中的表达及其与临床病理特征之间的关系。采用WB法检测中国人胃腺癌组织及其癌旁组织中HECW2蛋白水平以验证数据库中的分析结果。借助TIMER和Cibersort数据库分析HECW2与胃腺癌免疫浸润的关系。通过LinkedOmics数据库对胃腺癌中HECW2进行GO功能分析和KEGG信号通路富集分析及相关性基因分析。结果：生物信息学分析结果表明，33种不同类型肿瘤中，包括胃腺癌在内的12种肿瘤中HECW2呈显著高表达（均P<0.05），WB法结果显示，中国人胃腺癌组织中HECW2也呈显著高表达（P<0.05）。HECW2表达水平越高，胃腺癌患者OS越短，包括CD4+ T细胞、巨噬细胞、中性粒细胞和树突状细胞在内的免疫细胞浸润丰度越高（均P˂0.01）。此外，HECW2相关信号通路主要富集于细胞外基质受体相互作用、黏着斑、细胞黏附和氧化磷酸化等生理病理过程（均P˂0.01）。结论：HECW2在胃腺癌组织中呈显著高表达且其与胃腺癌预后不良和免疫细胞浸润密切相关，有成为胃腺癌预后标志物和治疗靶点的潜力。