目的：揭示共同性外斜视(XT)内直肌中关键的氧化应激相关基因和通路。

方法：对XT患者和正常对照者的内直肌标本进行RNA测序，应用包括差异表达基因的鉴定、功能富集分析、蛋白质互作网络构建和受试者工作特征曲线评估的生物信息学分析氧化应激相关的差异表达基因和通路。关键枢纽基因通过逆转录定量聚合酶链反应(RT-qPCR)进行验证。

结果：本研究纳入XT患者24例\〖男6例，女18例，年龄29.5(21.5，42.5)岁\〗，正常对照组14例\〖男4例，女10例，年龄42.0(28.0，55.0)岁\〗。共鉴定出319个氧化应激相关差异基因，功能富集分析显示其与活性氧代谢过程、对氧化应激的反应以及p53信号通路等显著相关。蛋白质-蛋白质互作网络分析确定了5个枢纽基因(IL6，TNF，CD4，PTPRC，ITGAM)。受试者工作特征曲线评估表明，CD4、PTPRC和ITGAM的表达水平对XT组和正常对照组的分类具有较高的准确性(AUC>0.9)； IL6和TNF的表达水平对XT组和对照组的分类呈现一定的准确性(0.7TNF、CD4和IL6在XT内直肌的显著差异表达(均P<0.05)。

结论：氧化应激可能在XT的发病机制中发挥重要作用，枢纽基因的发现为研究XT发病的分子机制提供了新的方向。

METHODS:RNA sequencing was performed on MR muscle specimens obtained from XT patients and healthy controls.Comprehensive bioinformatics, including the identification of oxidative stress-related differentially expressed genes(OSRDEGs), functional enrichment analysis, protein-protein interaction(PPI)network construction, and receiver operating characteristic(ROC)curve were used to analyze OSRDEGs and signaling pathways. Key hub genes were validated using reverse transcription-quantitative polymerase chain reaction(RT-qPCR).

RESULTS:A total of 24 XT patients \〖6 males, 18 females, age 29.5(21.5, 42.5)y\〗 and 14 healthy controls \〖4 males, 10 females, age 42.0(28.0, 55.0)y\〗 were enrolled.A total of 319 OSRDEGs were identified. Functional enrichment analysis revealed significant associations with the reactive oxygen species metabolic process, response to oxidative stress, and the p53 signaling pathway. PPI network analysis identified five hub genes(IL6, TNF, CD4, PTPRC,and ITGAM).ROC curve analysis demonstrated high diagnostic accuracy of CD4, PTPRC, and ITGAM(AUC>0.9)in distinguishing XT patients from healthy controls, while IL6 and TNF showed moderate diagnostic accuracy(0.7TNF,CD4, and IL6(all P<0.05).

CONCLUSION:Oxidative stress may play a vital role in the pathogenesis of XT. The identified hub genes provide new directions for investigating the molecular mechanisms underlying XT.