基于辨证论治的“证代偶联”临床疗效评价方法研究

Based on the study of 'the research on characteristic of the zheng with microvascular complications of diabetes' of National Tenth Five-Year Project, 'the research on Individual clinical evaluation of the zheng' of National Eleventh Five-Year Plan and 'the research on metabonomics of Yang deficiency with diabetic retinopathy' of National Natural Science Foundation, the study takes diabetes as research object , introduces the n-of-1 trial design ideas, in view of the dynamic change of diabetes basic syndromes Qi and Yin deficiency and it's partial/accompanying symptoms, set up the dynamic syndrome differentiation and treatment group, basic syndrome treatment group and non-syndrome differentiation and treatment group, through individual evaluation, group analysis, metabolic network construction、correlation analysis ,study the connotation of biology of syndrome and metabolic related differences, reveal the relationship between the dynamic changes of the syndrome and metabolomics, and then clear the static and dynamic association between syndrome and metabolomics; on the basis of the established diabetes syndrome-metabolomics data warehouse ,using neural networks, decision tree and other data analysis techniques, establish diabetes 'Syndrome-Metabolism Coupling' dynamic and static correlation model, determine the key evaluation index system of dynamic changes of the diabetes qi and Yin deficiency, ultimately establish the syndrome differentiation and treatment embodied 'Syndrome metabolomics efficacy evaluation'(Syndrome-Metabolism)., promot the objective and standardization of TCM clinical efficacy evaluation.

在国家十五攻关"糖尿病微血管病变证候特征研究"及十一五支撑计划"证候个体化临床评价研究"及自然科学基金"糖尿病视网膜病变阳虚病机的代谢组学研究"在基础上，以糖尿病为研究对象，采用单样本随机对照试验（n-of-1）设计思路，针对糖尿病基本证型气阴两虚及其偏/兼证动态变化，设立动态辨证论治、基本证型治疗和非辨证证论治疗组，动态采集受试者的证候、代谢组学和疾病信息，通过个体评价、群体分析，代谢网络构建、相关性分析研究证候及相关差异代谢物的生物学内涵，揭示证候与代谢组学动态变化之间的关系，进而明确证候代谢组学之间的动静态关联；在建立糖尿病证候-代谢数据仓库的基础上，运用神经网络、决策树等数据分析技术，建立糖尿病"证候代谢组偶联"动态及静态关联模型，确定糖尿病气阴两虚动态变化关键评价指标体系，最终确立体现辨证论治的"证候代谢组学疗效评价法"（证代法），推动中医临床评价客观化和标准化。

摘要.本研究分为三部分，第一部分以糖尿病及其微血管并发症为研究对象，共采集99例正常人，96例2型糖尿病患者，114例各期糖尿病视网膜病变患者，43例各期糖尿病肾病患者的证候信息及血清和尿液样本，运用GC-MS技术研究不同疾病患者的代谢组学差异。结果显示正常人、糖尿病、糖尿病视网膜病变及糖尿病肾病患者血清、尿液代谢组特征存在显著差异。第二部分在第一部分的基础上全面采集不同疾病患者的证候信息，将证候与代谢组学数据相关联，结果显示糖尿病及其微血管并发症基本证型气阴两虚及其偏/兼证患者间代谢组特征存在显著差异，初步明确了糖尿病及其微血管并发症相关证候的生物学基础。第三部分糖尿病视网膜病变为研究对象，采用单样本随机对照试验（n-of-1）设计思路，针对糖尿病视网膜病变基本证型气阴两虚及其偏/兼证动态变化，设立动态辨证论治和非辨证证论治疗组，动态采集受试者的证候、代谢组学和疾病信息，通过个体评价、群体分析，代谢网络构建、相关性分析研究证候及相关差异代谢物的生物学内涵，结果显示动态辨证论治组患者的代谢组学特征及证候特征较非辨证证论治疗组改善更为明显，提示动态辨证论治疗效优于非辨证证论。