环境因素与类风湿关节炎（rheumatoid arthritis，RA）的发生发展关系密切，但作用机制仍不清楚；我们前期和国内外的研究显示，RA寒热证的分类与气候、地域分布相关，但RA证候相关的生物学基础亟待研究。本研究在前期研究的基础上，以表观遗传学的重要修饰-羟甲基化（5hmC）为切入点，从表观遗传学角度将环境因素、RA寒热证分类及温阳通络方对寒证RA的作用效应机制有机联系起来，通过hMeDIP-seq和mRNA-seq技术检测寒热证及治疗前后的RA患者外周血单个核细胞基因5hmC和相应基因表达谱的变化，采用生物信息学分析联合实验验证的方法，筛选区分RA寒热证的关键基因/生物标志物及温阳通络方作用靶点，以期能揭示RA寒热证的分子生物学基础，同时阐述温阳通络方治疗寒证RA“病-证-方”对应的科学内涵。

The environmental factors are closely related to the occurrence and development of rheumatoid arthritis, but the mechanism is still unclear. The classification of RA cold and heat syndrome is related to climate and geographical distribution. However, the biological basis of RA syndrome is urgently needed to research. On the basics of DNA hydroxymethylation, We combined organically the environmental factors, RA cold and heat syndrome and the mechanism of wen-yang-tong-luo formula to treat RA, and detected the expression of 5hmC and mRNA of peripheral blood mononuclear cells in patients with RA and before and after treatment by hMeDIP-seq and mRNA-seq. According to the change of 5hmC and mRNA, bioinformatics analysis and experimental validation method will be used to screen the key genes / biomarkers and therapeutic target of wen-yang-tong-luo formula. This study will reveal the molecular basis of RA cold and heat syndrome, at the same time it will explain the etiological therapeutic mechanism of wen-yang-tong-luo formula.