近年来中药不良反应特别是传统无毒中药的肝毒性问题屡有报道，引起人们对中药安全性的严重担忧，与此同时其肝毒性的客观性在业内外也存在巨大争议。如何科学认知传统无毒中药的毒副作用已成为本领域最具挑战性的国际性难题。既往研究多拘泥于从药物角度寻找毒性物质及致毒机制，对可能由患者机体因素差异介导的中药肝毒性鲜有关注和研究。为此近年来申请者提出并建立基于临床功效的中药安全性评价策略和方法体系。本项目利用302医院丰富的药物性肝病临床资源，以风湿骨病治疗中成药—壮骨关节丸为研究载体，应用药物流行病学、网络药（毒）理学、药物基因组学等技术方法，以免疫调控为切入点，系统阐明机体病证因素与中药肝损伤易感性关系、毒性相关物质基础及损伤机制，筛查可能的易感人群及生物标志物，为临床对症治疗和安全用药提供科学依据和对策。在上述基础上，建立并完善基于临床病证的中药毒与效整合评价模式和方法，推动临床中药学的创新发展。

In recent years, adverse reactions of traditional Chinese medicine (TCM), especially nontoxic TCM, has been reported repeatedly, which has caused a matter of growing concern about the safety of TCM, while there is an argument about the objectivity of the hepatotoxicity. The issue “how to cognize the side effects of nontoxic TCM” has become one of the most challenging international problems in TCM safety research field. Previous research has mainly inquired the toxic substances and mechanism from the drugs, and few attentions has been paid to the organic factor-mediated drug induced liver injury. In recent years, the applicant proposed and established the safety evaluation strategy and method of traditional Chinese medicine based on clinical efficacy. This project select Zhuanggu Guanjie Pill, the Chinese medicine for the treatment of rheumatoid bone diseases, as the research subject and apply medicine epidemiology, network pharmacology (toxicology), pharmacogenomics and other technical methods to clarify the relationship between the immune factors and the liver injury susceptibility, and to screen susceptible populations and biomarkers with plentiful resources of drug-induced liver injury in 302 Hospital, in order to provide a scientific basis for the clinical safety of medication. On the basis of the study, the integrated evaluation method with toxicity and efficacy of TCM based on clinical disease and syndromes would be established and perfected for the development of the TCM toxicology theory.