中医药临床系统生物学是为适应中医药临床研究和转化医学的需要，以推动“系统-系统”模式的中医药现代化和国际化为目标，在中医药整体观和系统论指导下，整合运用多种系统生物学技术，通过对病、证诊疗方法和药物临床合理应用方法的创新研究来为临床服务，提高临床诊治水平的学科。针对现行研究中存在的“方、证、病割裂，基因、蛋白质、代谢物分离”等问题，我们提出构建以多层面生物标志物群为特征的临床系统生物学研究体系。整合的生物标志物群包括中医证候指标、临床生化及影像学指标、系统生物学标志物群多个层面，系统生物学指标包含基因、蛋白质、代谢物多个层次的标志物群。建立的整合生物标志物体系可应用于疾病早期预警、临床诊治、指导个性化用药、疾病预后以及药物评价。以近年来我们开展的糖尿病肾病中医药临床系统生物学研究为例，开展了包含中医证候指标和临床病理生化指标研究，还包括整体代谢指纹特征谱以及七大类百余种磷脂、15 种脂肪酸、21种嘌呤嘧啶、8 种硫醇氨基酸的定量指标和14 种糖尿病肾病相关基因在内的系统生物学研究，初步得出整合生物标志物群（IBS），应用于糖尿病肾病气阴两虚证的辅助诊断和糖肾方临床疗效评价，可为系统生物学应用于中医药临床研究和实践应用提供参考。以临床疗效为导向的中医药现代化研究是中医药发展的最佳途径。

Under the guidance of holism and systematic theory, clinical systems biology was proposed in order to accommodate the needs of traditional Chinese medicine (TCM) clinical research and translational medicine, which aims at promoting the modernization and internationalization of TCM with the "system-to-system" research mode. It was expected to enhance the level of diagnosis and treatment of diseases based on integrating various systems biology technology. And some innovation researches on the diagnosis and treatment methods of disease and syndrome, together with the method of drug rational application in clinic should be carried out in order to serve for clinic better. Considering the present problems in researches, such as "the formula, disease, and syndrome exist in isolation of their respective", as well as "the separation of gene, protein, metabolites as research subjects", the clinical systems biology research system should be constructed which characterized by multi -level biomarker group. The integrated biomarker system should be composed of multi-level indicators, including TCM syndrome indicators, clinic biomedical indicators, imaging indexes as well as systems biology biomarker groups. And the systems biology biomarker groups should contain multi-level biomarkers, such as gene, protein and metabolites. The established integrated biomarker system can be applied to early warning of disease, clinical diagnosis and treatment, personalized medicine, disease prognosis as well as the efficacy evaluation. The recently TCM clinical systems biology research on diabetic nephropathy of our group was used as an example in this paper to introduce the proposed idea. The tentative integrated biomarker system (IBS) has been discovered and screened on the basis of TCM syndrome indicators, clinic biomedical indicators, together with some systems biology biomarkers, which obtained by metabolic profiling analysis, quantitative analysis of fifteen fatty acids, twenti-one purine and pyrimidine and eight mercaptan amino acid, as well as the fourteen diabetic nephropathy related gene. The established IBS can be used for the auxiliary diagnosis of diabetic nephropathy with Qi and Yin deficiency as well as the efficacy evaluation of Tangshen formula. The refered research would provide relevant reference material for the application of systems biology on TCM clinic research and practice. Clinically directive strategies on modernization research of traditional Chinese medicine should be the best way for the development of TCM.

国家自然科学基金重点项目（81130066）：基于整体观的中药复方（糖肾方）“系统-系统”的现代基础研究，负责人：罗国安。