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 血清同型半胱氨酸（Hcy）水平与慢性肾脏病（CKD）的进展相关,但中年人群的非线性关联研究较少,本研究旨在寻找慢性肾脏病危险因素。方法 本研究基于NHANES 1996—2006年数据,纳入5 361例45~65岁参与者,以估算肾小球滤过率（eGFR）<60 mL/（min·1.73 m²）和尿白蛋白/肌酐比值（uACR）≥30 mg/g评估肾功能下降。结果 通过逻辑回归及平滑曲线拟合分析发现,Hcy每升高1 µmol/L,eGFR降低的风险增加8%（OR=1.08,95%CI：1.06~1.10）,uACR升高的风险增加2%（OR=1.02,95%CI：1.00~1.04）。非线性分析显示,Hcy对eGFR的阈值效应拐点为13.4 µmol/L（拐点左侧OR=1.59,95%CI：1.49~1.70;右侧无显著关联）。亚组分析表明,性别、高血压、糖尿病等协变量无交互作用,然而,在敏感性分析中,糖尿病患者中Hcy与eGFR降低的关联更强（交互P=0.015 8）。结论 本研究提示,控制Hcy水平或可延缓美国中年人群（尤其是糖尿病患者）的肾功能衰退。

Objective Elevated serum homocysteine（Hcy）levels are linked to chronic kidney disease（CKD）progression,yet the nonlinear relationship in middle-aged populations remains underexplored．Methods This study analyzed data from 5 361 participants aged 45-65 years in the NHANES 1996-2006 cohort．Renal dysfunction was defined as an estimated glomerular filtration rate（eGFR）<60 mL/min/1.73 m² and urinary albumin-to-creatinine ratio（uACR）≥30 mg/g．Results Logistic regression and smoothed curve fitting revealed that each 1 µmol/L increase in Hcy elevated the risk of reduced eGFR by 8%（OR=1.08,95% CI：1.06-1.10）and uACR by 2%（OR=1.02,95% CI：1.00-1.04）．A nonlinear threshold effect was identified at 13.4 µmol/L,with a stronger association below this threshold（OR=1.59,95% CI：1.49-1.70）and no significant effect above it．Subgroup analyses showed no interactions with gender or hypertension,but a stronger Hcy-eGFR association was observed in diabetics（interaction P=0.0158）．Conclusions These findings suggest that controlling Hcy levels may mitigate renal decline,particularly in diabetic populations,warranting further causal investigations．

目的 探讨代谢综合征(metabolic syndrome, MS)(指包括高血压,糖尿病,高脂血症和腹型肥胖的一组综合征)在中国南方老年病人的患病率、及其与心血管事件和痴呆关系。方法 本研究为一个中国南方老年人代谢综合征的横断面研究。我们采集了患者的病史、人口学和生化资料。对比生化资料、心血管事件、痴呆等疾病在MS组和非MS组中的差异,并使用Logistic回归分析来寻找MS的独立影响因子。结果 本研究共纳入206例患者。其中有92(44.66%)例患者符合代谢综合征的诊断标准。女性在MS组中35例(38.04%)明显高于在非MS组中28例(24.56%)。整体年龄(86.74± 6.10),在MS组(86.37±5.74)和非MS组(87.04±6.38)对比中无统计学意义。生化资料对比中,白细胞[(7.46±2.38) vs (6.46±2.35),P=0.003]和血肌酐[94.50(68.50, 129.33) vs 78.00(64.50, 99.75),P=0.004]在MS组中较高。Logistics单因素回归分析及多因素回顾分析提示白细胞、血肌酐和女性为MS的独立风险因子。心肌梗塞(35例,38.04%和心绞痛(28例, 24.56%)在MS组中明显高于非MS组中心肌梗塞(10例,8.77%)和心绞痛(39例,34.21%),两组比较有统计学意义,Logistics回归分析发现MS是心肌梗塞和心绞痛的独立影响因子;但是心衰和中风在两组对比中无统计学差别。痴呆(包括老年性痴呆和血管性痴呆)在MS组中明显低于非MS组:26例(28.26%)vs 50例(43.86%),提示MS可能对痴呆有预防作用。结论 MS在中国南方老年患者中普遍存在,女性、白细胞、血肌酐为MS的独立影响因子;MS是心肌梗塞和心绞痛的独立影响因子;MS中痴呆明显低于非MS组,可能对痴呆有预防保护性作用。

Objective To study the prevalence and correlation between the metabolic syndrome MS (including hypertension, diabetes, hyperlipidemia and obesity) with cardiovascular and dementia in the elderly people of south China. Methods This cross-sectional research studied metabolic syndrome of the elderly in south China. We collected the demographics and chemotic data and compared them in MS and non-MS group. And Logistic regression was used to analyze the independent factor of MS and the relationship between MS and the cardiovascular disease and dementia. Results This study included 206 patients and 92 (44.66%) of them were diagnosed as MS. 35 patients (38.04%) in MS group were female and 28 female cases (24.56%) in non-MS group. The mean age of the sample was (86.74±6.10) and the comparison between the MS group (86.37±5.74) and non-MS group (87.04±6.38) was not significantly different. White blood cell (WBC) (7.46±2.38 vs 6.46±2.35,P=0.003) and serum creatinine (Scr) was significantly [94.50(68.50,129.33) vs 78.00(64.50, 99.75),P=0.004]in MS group versus in non-MS group. Single factor and Multinomial logistic regression found WBC, serum creatinine and female gender were the independent risk factors of MS. Myocardial infarction (35, 38.04%) and angina (28, 24.56%) were significantly higher in MS group than that in non-MS group (10, 8.77%) and (39, 34.21%), respectively, with P<0.05. Logistic regression found MS was an independent risk factor of myocardial infarction and angina but not in heart failure and stroke. Dementia (including Alzheimer disease and vascular dementia) was found lower in MS group (26, 28.26%) than that in non-MS group (50, 43.86%), the difference was significant and this means MS could be protective for dementia. Conclusion MS is prevalent in the elderly of south China. Female gender, WBC and Scr were independent factors of MS; MS was the independent risk factor of myocardial infarction and angina; dementia was significantly lower in MS group, implying MS could be protective to dementia.

       目的   血清同型半胱氨酸（Hcy）水平与慢性肾脏病（CKD）的进展相关，但中年人群的非线性关联研究较少，本研究旨在寻找慢性肾脏病危险因素。方法   本研究基于NHANES 1996—2006年数据，纳入5 361例45~65岁参与者，以估算肾小球滤过率（eGFR）＜60 mL/（min·1.73 m² ）和尿白蛋白/肌酐比值（uACR）≥30 mg/g评估肾功能下降。结果   通过逻辑回归及平滑曲线拟合分析发现，Hcy每升高1 µmol/L，eGFR降低的风险增加8%（OR=1.08，95%CI：1.06~1.10），uACR升高的风险增加2%（OR=1.02，95%CI：1.00~1.04）。非线性分析显示，Hcy对eGFR的阈值效应拐点为13.4 µmol/L（拐点左侧OR=1.59，95%CI：1.49~1.70；右侧无显著关联）。亚组分析表明，性别、高血压、糖尿病等协变量无交互作用，然而，在敏感性分析中，糖尿病患者中Hcy与eGFR降低的关联更强（交互P=0.015 8）。结论   本研究提示，控制Hcy水平或可延缓美国中年人群（尤其是糖尿病患者）的肾功能衰退。

        Objective   Elevated serum homocysteine（Hcy）levels are linked to chronic kidney disease（CKD）progression，yet the nonlinear relationship in middle-aged populations remains underexplored．Methods  This  study analyzed data from 5 361 participants aged 45–65 years in the NHANES 1996–2006 cohort．Renal dysfunction was defined as an estimated glomerular filtration rate（eGFR）＜60 mL/min/1.73 m²  and urinary albumin-to-creatinine ratio（uACR）≥30 mg/g．Results  Logistic regression and smoothed curve fitting revealed that each 1 µmol/L increase in Hcy elevated the risk of reduced eGFR by 8%（OR=1.08，95% CI：1.06–1.10）and uACR by 2%（OR=1.02，95% CI：1.00–1.04）．A nonlinear threshold effect was identified at 13.4 µmol/L，with a stronger association below this threshold（OR=1.59，95% CI：1.49–1.70）and no significant effect above it．Subgroup analyses showed no interactions with gender or hypertension，but a stronger Hcy-eGFR association was observed in diabetics（interaction P=0.0158）．Conclusions  These findings suggest that controlling Hcy levels may mitigate renal decline，particularly in diabetic populations，warranting further causal investigations．