目的   免疫球蛋白A肾病（IgAN）与炎症性肠病（IBD）的相互作用机制尚未阐明。本研究旨在解析IBD与IgAN共病的关键特征基因及核心信号通路，以揭示肠－肾轴的分子调控网络。方法   于GEO数据库获取IBD（GSE75214）和IgAN（GSE93798）基因表达谱，筛选差异表达基因（DEGs）。通过蛋白互作网络（PPI）和拓扑算法（MCC、MNC、Degree、EPC等）识别核心特征基因，并结合公共数据库（CTD、DISEASES和GeneCards）和单细胞转录组测序（GSE171314）进行验证。通过Nephroseq数据库验证基因表达与临床表型的相关性。结果   共筛选出17个IBD-IgAN共病DEGs，PPI网络分析等确定以FOS、EGR1、CXCL2和JUNB为核心特征基因。功能富集分析显示白细胞介素-17（IL-17）信号通路显著激活。单细胞测序验证FOS、EGR1、CXCL2和JUNB基因在IgAN特异性高表达，并通过Nephroseq数据库验证其与尿蛋白和估算的肾小球滤过率下降（eGFR）显著相关。结论  本研究揭示IBD与IgAN共享IL-17通路异常激活及FOS、EGR1、CXCL2和JUNB的基因网络，为开发基于肠－肾轴调控的靶向治疗策略提供理论依据。

       Objective  The complex interplay between immunoglobulin A nephropathy（IgAN）and inflammatory bowel disease（IBD）remains poorly understood．This  study  aimed to identify  key  cross-talk  genes  and  pivotal  signaling pathways shared between IBD and IgAN，thereby elucidating the molecular regulatory network underlying the gut-kidney axis．Methods  Transcriptomic datasets for IBD（GSE75214）and IgAN（GSE93798）were retrieved from the GEO database．Differentially expressed genes（DEGs）were screened，and shared DEGs were intersected．Protein-protein interaction（PPI）networks were constructed using STRING and Cytoscape，with topological algorithms applied to identify hub genes．Gene expression profiles were validated through（CTD，DISEASES and GeneCards）and single-cell RNA sequencing（GSE171314）and the Nephroseq database，focusing on clinical correlations with proteinuria and estimated glomerular filtration rate（eGFR）．Results  Seventeen shared DEGs were identified between IBD and IgAN．PPI network analysis revealed FOS，EGR1，CXCL2 and JUNB as core hub genes．Functional enrichment analysis demonstrated significant activation of the interleukin-17（IL-17）signaling pathway．Single-cell sequencing confirmed the specific upregulation of these genes in renal tubular epithelial cells of IgAN patients，which was further validated to correlate with proteinuria and eGFR decline．Conclusions  IBD and  IgAN share aberrant activation of the IL-17 pathway and a co-regulatory gene network involving FOS，EGR1，CXCL2 and JUNB，providing a theoretical foundation for developing therapeutic strategies centered on the gut-kidney axis．

目的 评估调脂药物靶点所介导的脂质表型（HMGCR、PCSK9和NPC1L1）与高血压肾病风险之间潜在的因果相关性。方法 使用来自欧洲人群公开可获得的全基因组关联研究（GWAS）汇总数据进行孟德尔随机化（MR）分析。采用与低密度脂蛋白胆固醇（LDL-C）相关的遗传变异,根据选定的调脂药物靶基因筛选工具变量,使用逆方差加权法作为主要MR分析方法,并进行敏感性分析确保结果的稳健性。结果 基因预测的LDL-C水平与较高的高血压肾病风险相关（OR=1.19,95% CI：1.03~1.38,P=0.021）。较高的HMGCR介导的LDL-C水平与高血压肾病风险存在正向因果相关性（OR=4.08,95% CI：2.86~5.81;P<0.001）。然而,PCSK9和NPC1L1介导的LDL-C水平与高血压肾病风险无相关性。Cochran Q检验、MR-PRESSO检测和MR-Egger截距测试显示工具变量之间不存在异质性或水平多效性。结论 HMGCR介导的LDL-C与高血压肾病的发病风险存在因果相关性,针对HMGCR基因的他汀类药物在高血压肾病的防治中可能具有潜在益处。

Objective To assess the potential causal relationship between lipid phenotypes mediated by lipid-lowering drug targets（HMGCR,PCSK9 and NPC1L1）and the risk of hypertensive nephropathy．Methods Mendelian randomization（MR）analysis was conducted using summary data from publicly available European ancestry genome-wide association studies（GWAS）．Genetic variants associated with low-density lipoprotein cholesterol（LDL-C）were used as instrumental variables based on selected lipid-lowering drug target genes screening tools．Inverse variance weighting was selected as the main MR analysis method,with sensitivity analyses conducted to ensure the robustness of the results．Results Genetically predicted LDL-C levels were associated with a higher risk of hypertensive nephropathy（OR=1.19,95% CI：1.03~1.38,P=0.021）．Higher LDL-C levels mediated by HMGCR were positively causally related to increased risk of hypertensive nephropathy（OR=4.08,95% CI：2.86~5.81;P<0.001）．However,LDL-C levels mediated by PCSK9 and NPC1L1 showed no significant association with the risk of hypertensive nephropathy．Cochran’s Q test,MR-PRESSO,and MR-Egger intercept tests showed no heterogeneity or horizontal pleiotropy among instrumental variables．Conclusions The findings of this study support the causal relationship between LDL-C mediated by HMGCR and increased risk of hypertensive nephropathy,suggesting potential benefits of statin therapy for hypertensive nephropathy．

目的 探讨ε-3多不饱和脂肪酸在胃肠道肿瘤患者化疗后的胃肠道毒性及生活质量的作用。方法 在研究前经过化疗筛选,按照WHO化疗副反应在2级或者以上的50名住院的胃癌或者直结肠癌患者,随机分为对照组(单纯化疗)(n=25)和研究组(化疗加ε-3多不饱和脂肪酸)(n=25),两组的化疗方案均为化疗筛选的方案。预防性每天静脉使用ε-3多不饱和脂肪酸 200 mg,连续5天,记录评估胃肠道并发症,如恶心、呕吐和腹泻,以及KPS评分、血清白蛋白、IL-2、IFN-γ和CRP。结果 与对照组比较,恶心、呕吐和腹泻评分、IL-2、IFN-γ和CRP低于于对照组,相反,生活质量评分研究组高于对照组,差异有统计学意义(P<0.05)。结论 预防性使用ε-3多不饱和脂肪酸能够减轻胃肠道肿瘤患者化疗后的胃肠道毒性症状、降低全身炎症因子反应并改善生活质量。

Objective To explore the effect omega-3polyunsaturated fatty acid omega-3 FA on clinical manifestations of gastrointestinal toxicity and quality of life (QOL) induced by chemotherapy for patients with gastric or colorectal cancer. Methods After screening chemotherapy, Fifty patients with gastric or colorectal cancer, according to developing WHO side-effect grading system of grade 2 or higher were randomly divided into either control group (n=25) or omega-3 FAs group (n=25) during next cycle of chemotherapy. In the control group, the patients received the same chemotherapy regimens as screening cycle and in the omega-3 FA group, received chemotherapy and omega-3 FAs. Prophylactic intravenous 200 mL /d was given for 5 days. The gastrointestinal complications such as nausea,vomiting or diarrhoea and Karnofsky performance status(KPS ),IL-2,IFN-γandCRP,ect, were evaluated respectively. Results Compared with the control group, the scores of nausea vomiting and diarrhea and IL-2,IFN-γor CRP levels decreased , significantly,on the contrary, the score of QOL increased. There was significantly statistical difference (P<0.05). Conclusion Prophylactic intravenous omega-3 FA can ameliorate clinical manifestations of gastrointestinal toxicity and systemic inflammatory response syndrome(SIRS) induced by chemotherapy and improve QOL for patients with gastric or colorectal cancer.