目的  压疮是指由于组织受压时间过长引起的严重并发症，2025年的数据显示，压疮在活动受限患者中发生率高。机体代谢紊乱可能会引起压疮，但是否与血清代谢物有因果影响，暂不明确。方法   本文运用孟德尔随机化（MR）方法评价血清代谢物与压疮间风险因素，基于MR方法评价血清代谢物和压疮的因果联系，分别纳入由欧洲人群全基因组关联研究（GWAS）。压疮：FinnGen R10，3 167例；血清代谢物：EMBL-EBI数据库16种代谢物数据作为研究样本；筛选条件：工具变量筛选条件［P＜5×10^-8，连锁不平衡聚类r ² ＜0.001，kb=10 000，F统计量＞10（公式：F=R² ×N-2/1-R² ）］；主要分析方法：使用（IVW）法，辅助采用加权中位数法（WM）、MR-Egger回归法校验；用Benjamini-Hochberg法进行多重检验校正（FDR＜0.05为有统计学意义）。结果  共鉴定出10种代谢物与压疮存在关联（P＜0.01），经FDR校正后4种：代谢物18：2/20：4n6的水平升高（P＜0.000 2）2-Oxopeptide的作用相反，降低压疮的风险（OR=0.73，95%CI：0.59~0.92，P=0.011）；琥珀酸可增加压疮的风险（OR=1.13，95%CI：1.03~1.24，P=0.018）；甘氨酸/丙氨酸比值降低压疮风险（OR=0.849，95%CI：0.76~0.93，P=0.022）。稳定性分析证明上述发现是可信的、稳健的（heterogeneity：P＞0.05，pleoitropy：P＞0.05）。结论  血清代谢物通过调控炎症反应、影响微循环障碍以及干预能量代谢途径，参与压疮的发生发展，可作为构建压疮风险的模型以及制定相关干预策略为压疮评估、治疗、预防提供因果层面的理论依据。

      Objective  Pressure ulcer（PU）is a serious complication caused by prolonged tissue compression．Data of 2025 shows that PUs have a high incidence among patients requiring long-term bed rest．Metabolic disorders may contribute to PU development，but whether serum metabolites causally affect PU risk remains unclear．Methods  this study employed the Mendelian randomization（MR）method to evaluate whether serum metabolites are risk factors for PU．To assess the causal relationship between serum metabolites and PU，data from Genome-Wide Association Studies（GWAS）of European populations were included：PU data from FinnGen R10（3 167 cases）and data on 16 serum metabolites from the EMBL-EBI database．Instrumental variable screening criteria were as follows：P＜5×10^-8，linkage disequilibrium clustering（r ² ＜0.001，kb=10，000），and F-statistic ＞10（Formula：F=［R² ×N-2］/［1-R² ］）．The inverse variance weighting（IVW）method was used as the primary analytical approach，supplemented by the weighted median（WM）method and MR-Egger regression for verification．The Benjamini-Hochberg method was applied for multiple test correction（FDR＜0.05 was considered statistically significant）．Results  A total of 10 metabolites were identified to be associated with PU（P＜0.01），and 4 remained significant after FDR correction：elevated levels of metabolite 18：2/20：4n6（P＜0.0002）；2-Oxopeptide exerted an opposite effect，reducing PU risk（OR=0.73，95%CI：0.59-0.92，P=0.011）；succinic acid increased PU risk（OR=1.13，95%CI：1.03-1.24，P=0.018）；and the glycine/alanine  ratio  reduced PU risk（OR=0.849，95%CI：0.76-0.93，P=0.022）．Stability analysis（PH-TauNE［novel pleiotropy test］） confirmed that the above findings were credible and robust（heterogeneity：P＞0.05，pleiotropy：P＞0.05）．Conclusions  Serum metabolites are involved in the occurrence and development of PU by regulating inflammatory responses，affecting microcirculatory disorders，and interfering with energy metabolism pathways．They can provide causal theoretical basis for constructing PU risk prediction models，formulating relevant intervention strategies，and guiding PU treatment，prevention，and assessment．

       目的   探讨溶酶体相关膜蛋白3（LAMP3）与肾癌发病风险之间的因果关系，为肾癌的分子致病机制提供新的理论依据。方法   基于全基因组关联研究（GWAS）数据，采用孟德尔随机化分析方法，评估LAMP3基因表达与肾癌的因果关系。并通过GEPIA2分析LAMP3表达对肾癌总体生存期（OS）及无病生存期（DFS）的关系。结果  LAMP3基因变异与肾癌风险呈正相关，提示LAMP3的表达可能增加肾癌的发病风险。此外，GEPIA2分析进一步显示，LAMP3的高表达与肾癌患者的低总体生存期（OS）及无病生存期（DFS）显著相关。结论   本研究通过孟德尔随机化分析探讨了LAMP3基因表达与肾癌的因果关系，结果表明LAMP3可能是肾癌的潜在致病因子，并与肾癌预后相关。这为肾癌的分子致病机制研究提供了重要的理论依据，并为未来的生物标志物和靶向治疗策略的开发提供了新的思路。

        Objective  To investigate the causal  relationship  between LAMP3 expression and  renal cancer  risk  using Mendelian randomization analysis，providing a theoretical basis for understanding the molecular mechanisms underlying renal cancer．Methods  This study utilized data from genome-wide association studies（GWAS）and employed Mendelian randomization analysis to assess the causal relationship between LAMP3 gene expression and renal cancer．Additionally，GEPIA2 was used to examine the association between LAMP3 expression and overall survival（OS）and disease-free survival（DFS）in renal cancer patients．Results  Variants in the LAMP3 gene were positively correlated with renal cancer risk，suggesting that LAMP3 expression may increase the likelihood of developing renal cancer．Furthermore，GEPIA2 analysis  revealed that high expression of LAMP3 was significantly associated with lower OS and DFS in renal cancer patients．Conclusions  This study explored the causal  relationship between LAMP3 gene expression and renal cancer through Mendelian randomization analysis．The results indicate that LAMP3 may be a potential pathogenic factor in renal cancer and is associated with poor prognosis．These findings provide important theoretical insights into the molecular mechanisms of  renal cancer and offer new perspectives for the development of biomarkers and targeted therapeutic strategies in the future．

      目的   采用两样本孟德尔随机化以及Meta分析研究趋化因子C-X3-C基序配体1（CX3CL1）表达水平与系统性红斑狼疮（SLE）发病风险的因果关系。方法   获取CX3CL1表达水平与SLE的全基因组关联研究（GWAS）数据，将单核苷酸多态性（SNP）作为工具变量并选择敏感的SNPs进行分析。通过逆方差加权法（IVW）、加权中位数法（WM）、MR-Egger回归法进行两样本MR分析，以OR值评估CX3CL1表达水平与SLE之间的因果关系，并对结果进行异质性和多效性检验。最后利用R软件Meta包进行Meta分析。利用coloc包进行共定位分析。结果   纳入9个SLE作为结局变量，其中4个变量ebi-a-GCST90018917（OR=2.14，95%CI：1.50~3.06），ebi-a-GCST003156（OR=2.25，95%CI：1.00~5.06），ebi-a-GCST90014238（OR=3.02，95%CI：1.54~5.94），finn-b-SLE_NOS（OR=1.81，95%CI：1.01~3.22）表明CX3CL1表达水平与SLE之间存在因果关系。关于 OR 95% CI 的森林图显示 SLE 患者的CX3CL1表达水平显著高于健康人群（OR=1.87，95%CI：1.53~2.29，P＜0.001）。共定位分析结果提示CX3CL1表达水平和SLE表型之间有共享的遗传变异位点（rs170364）。结论  CX3CL1表达水平与SLE存在正向因果关系，CX3CL1表达水平的升高使得SLE的发病风险升高。

       Objective  To investigate the causal  relationship  between CX3CL1 levels and the  risk of  systemic lupus erythematosus（SLE）using two-sample Mendelian randomization and Meta-analysis methods．Methods  Genome-Wide Association Study（GWAS）data for CX3CL1 levels and SLE were obtained．Single nucleotide polymorphisms（SNPs）were used as instrumental variables，and sensitive SNPs were selected for analysis．Two-sample Mendelian  randomization was performed using the inverse variance weighted（IVW）method，weighted median（WM）method，and MR-Egger  regression to evaluate the causal relationship between CX3CL1 levels and SLE，with OR values assessing this relationship．Heterogeneity and pleiotropy tests were conducted on the results．Meta-analysis was performed using the Meta package in R software，and colocalization analysis was conducted using the coloc package．Results  Nine SLE outcomes were included as outcome variables，with four variables（ebi-a-GCST90018917［OR=2.14，95%CI：1.50-3.06］，ebi-a-GCST003156［OR=2.25，95%CI：1.00-5.06］，ebi-a-GCST90014238［OR=3.02，95%CI：1.54-5.94］，finn-b-SLE_NOS［OR=1.81，95%CI：1.01-3.22］）indicating a causal relationship between CX3CL1 expression levels and SLE．The forest plot for OR 95%CI showed that CX3CL1 expression levels in SLE patients were significantly higher than in healthy individuals（OR=1.87［95%CI：1.53-2.29］，P＜0.001）．Colocalization analysis suggested that there was shared genetic variation sites（rs170364）between CX3CL1 expression levels and SLE phenotype．Conclusions  There is a positive causal relationship between CX3CL1 expression levels and SLE，with increased CX3CL1 levels elevating the risk of developing SLE．

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．