乌头汤和白虎加桂枝汤来自《金匮要略》，分别为治寒痹、热痹代表方，临床治疗类风湿性关节炎（RA）疗效确切，但作用原理不明。本项目遵循“以方测证”和“以证验方”的思路 ，采用有别于以往单纯的还原分析模式，将宏观、微观多层次信息挖掘与融合，采用“计算与验证相配合、组学数据与传统药理学结果相印证、多组分药物体内过程与方剂物质基础相对应”的研究策略，将来自临床样本的全基因组表达谱分析数据和网络计算结果进行整合，获得RA寒、热病证分子网络靶标。在此基础上，比较乌头汤和白虎加桂枝汤候选靶标分别对RA寒、热病证分子网络的干预潜能，揭示其矫正不同病证失衡网络的作用机制。同时，通过多维度多层次的体内外方法，进一步明确其关键药效靶标和物质基础。相关研究结果将有助于揭示基于“病-证-方”关联的方剂科学内涵并指导临床实践，为同病异治机制研究提供新策略，对中医药基础理论的创新发展及现代中药新药研制也意义重大。

Wutou decoction and Baihu guizhi decoction, both recorded in “Synopsis of Golden Chamber”, are separately representative formulae in arthromyodynia with cold and hot pattern therapy. In clinics, definite therapeutic effects could be achieved when these two formulae are used for the treatment of rheumatoid arthritis (RA). However, the underlying mechanisms remain unclear. Following the thread of “syndrome differentiation through formula effect assessments” and “formula effect evaluation through syndrome differentiation”, this project integrates the whole genome expression profiling data from clinical samples and network computing results to obtain the molecular network targets of RA and RA cold/hot patterns by conducting data mining and fusion at both macroscopic and microscopic multi-levels, which are distinct from the simple regression analysis model previously. In the precise, this strategy is performed by the combination of calculation and verification, the confirmation of proteomics data and traditional pharmacology results, and the correspondence of in vivo process of multi-component medicines and material base of formulae. On this basis, the action mechanisms of the rectification of formulae on different disease-syndrome imbalance networks are revealed, by comparing the potential interventions of candidate targets of wutou decoction and Baihu guizhi decoction on the molecular networks of RA and RA cold/hot patterns. Meanwhile, this multi-dimension and multi-level in vivo and in vitro approach also further elucidates key pharmacodynamics-associated targets and material base of these formulae. The relevant research results could be beneficial to reveal the complex scientific connotation of formulae that are based on “disease-syndrome-formula” relations, provide guidance to the clinical practice, present a new strategy for the studies of treating the same disease with different medicines” theories, and notably, make a difference to the innovation development of basic theories of traditional Chinese medicines, as well as the researches and production of modern Chinese drugs.