基于复杂生物网络技术的慢性萎缩性胃炎湿热证诊断模型构建

Chronic atrophic gastritis is a common and intractable disease of the digestive system. Because of it has a certain possibility of canceration, which attracted much attention from academic. Traditional Chinese medicine has a unique advantage for this disease. The incidence of Dampness-Heat syndrome in the disease is more than 70%, which throughout the whole process of the disease. However, the macroscopic syndrome differentiation of Dampness-Heat syndrome based on the four diagnostic methods is subjective, while microscopic syndrome differentiation based on systematic biology is a useful supplement. Therefore, based on the previous studies, this research proposes the hypothesis that "based on the macroscopic four diagnostic information and the biological complex network of gut microflora, tongue coat and urine metabolic markers, it is helpful for the accurate diagnosis and treatment of Dampness syndrome." This study intends to make use of multidisciplinary crossover techniques such as gut microbiology and metabonomics to build a diagnostic model combining macroscopic four diagnostic information and microscopic indices of typical Dampness-Heat syndrome of chronic atrophic gastritis based on complex biological network technology. The result of the research will be helpful for the accurate diagnosis of Dampness-Heat syndrome, And the development of automatic diagnosis system with independent intellectual property rights.

慢性萎缩性胃炎是消化系统常见的疑难病症，因其存在一定癌变概率，而备受学术界关注，中医药对其治疗具有独特的优势。湿热证在该病中患病率在70%以上，贯穿于该病的始终。但基于四诊信息的湿热证宏观辨证主观性强，而基于系统生物学的微观辨证是其有益的补充。因此，本课题在前期研究基础上，提出假说“基于宏观四诊信息和肠道菌群微生态及舌苔、尿液代谢标志物共同构成的生物复杂网络有助于湿热证的精准诊疗”。本研究拟借助肠道微生物组学和代谢组学等多学科交叉技术，基于复杂生物网络技术构建慢性萎缩性胃炎典型湿热证的宏观四诊信息和微观指标结合的诊断模型，为湿热证精准诊断和个体化诊疗奠定理论和方法学基础，为开发自动辅助诊断系统提供有益的积累。

慢性萎缩性胃炎是胃癌的癌前疾病，我国的发病率约为25.8%，中医药对其治疗具有独特的优势。脾胃湿热证为慢性萎缩性胃炎临床常见证候，贯穿于该病的始终。本研究借助微生物组学、代谢组学、生物信息学等多学科交叉技术和方法，共完成四方面研究内容，①收集典型慢性萎缩性胃炎脾胃湿热证、脾胃虚寒证及健康对照组有效粪便样本174例，有效舌苔样本102例；②基于多种数据挖掘方法对脾胃湿热证宏观症状（体征）进行主症筛选，共获得7个主症，其中正相关4个（苔黄、苔腻、舌色红、苔厚），预测准确率为89.4%；③基于16SrRNA高通量测序和超高液相色谱-质谱联用技术（LC-MS）进行肠道菌群、粪便代谢物、舌苔菌群及其代谢物检测，并运用随机森林和ROC曲线对差异物质进行筛选和诊断效果评价，发现慢性萎缩性胃炎脾胃湿热证最具潜力的诊断标志物为1个肠道菌群（放线菌属），3个粪便代谢物（壬二酸、9-十六碳烯酸、十五酸），3个舌苔菌属（g__TM7x、嗜血杆菌、梭菌属）和3个舌苔代谢物（苯乙酸、吲哚乙酸、对羟基苯乙酸），这些诊断标志物对脾胃湿热证诊断具有一定的灵敏度和特异度；④基于共线性网络对慢性萎缩性胃炎脾胃湿热证宏观症状（体征）和微观诊断标志物进行关联分析，并构建了脾胃湿热证宏观症状（体征）与肠道菌群、粪便代谢物、舌苔菌群及其代谢物诊断标志物结合的复杂网络。本研究为脾胃湿热证精准诊断和个体化诊疗奠定理论和方法学基础，为开发具有自主知识产权的自动辅助诊断系统提供有益的积累。共发表标注论文18篇，标注期刊论文11篇，其中SCI收录2篇，CSCD收录9篇；标注会议论文7篇，EI收录1篇；主编专著1部，获得发明专利1项；参加国内外学术会议8次，受邀大会报告6次，培养毕业研究生5名，获得学术会议优秀论文奖一等奖2名，二等奖1名，优秀奖2名。