基于关联规则挖掘仝小林院士《脾瘅新论》用药规律

The prescription rule analysis of the New Theory on Spleen Dampness Syndrome by Academician TONG Xiaolin

目的采用医案数据挖掘的方法对《脾瘅新论》中脾瘅虚损阶段医案的基本特征、用药特色、组方规律、药症关系等进行分析。方法收集《脾瘅新论——代谢综合征的中医认识及治疗》2004年1月—2016年12月脾瘅虚损阶段病例,采集医案中患者基本信息、临床症状体征、实验室检查、中西医诊断、治法、方药等。采用Epidata 3.1数据管理软件建立医案数据库,采用SPSS Modeler 14.2统计软件中提供的Apriori算法对药物与药物、药物与症状、药物与西医指标进行关联规则分析。结果(1)共纳入医案51个,所涉证型17种,频次≥3的前三位有痰瘀互结、胸阳痹阻,脾气虚弱、瘀血阻络,脾虚内热、经络湿寒;治法14种,频次≥3的前三位有通阳泄浊、豁痰宣痹,健脾益气、化痰通络,温阳益气、散寒通痹;处方15首,频次≥3的前三位有黄芪桂枝五物汤、瓜蒌薤白半夏汤、干姜黄芩黄连人参汤;共用药物83味,药物总频数476次,频次≥15的有黄连、黄芪、酒大黄、鸡血藤、生姜、黄芩、桂枝。(2)药物-药物关联规则按支持度≥15%,置信度=100%,分析出二阶关联规则7条,三阶关联规则7条,四阶关联规则6条,其中各关联规则排名第一的分别是:“黄芩→黄连”“干姜+黄芩→黄连”“白芍+桂枝+鸡血藤→黄芪”;药物-症状关联规则按支持度≥5%,置信度=100%,分析出二阶关联规则8条,三阶关联规则31条,四阶关联规则30条,其中各关联规则排名第一的是:“黄芪→肢体水肿”“桂枝+鸡血藤→肢体麻木疼痛”和“桂枝+鸡血藤+黄芪→肢体麻木疼痛”;药物-西医指标二阶关联规则按支持度≥5%,置信度=100%,分析出二阶关联规则5条,三阶关联规则16条,四阶关联规则16条,其中各关联规则排名第一的分别是:“秦皮→尿酸”“黄连+干姜→糖化血红蛋白”和“黄连+干姜+黄芩→糖化血红蛋白”。结论通过关联规则分析方法客观量化地展示了仝小林院士治疗脾瘅病虚损阶段医案的药物-药物、药物-症状和药物-理化指标的组合规律,脾瘅虚损阶段使用“态靶”辨证方法,药物组合以“小方”为特色,用药针对患者症状体征(“症靶”)及西医指标(“标靶”)。该研究可为进一步研究仝小林院士的学术思想和用药经验提供参考。

Objective To analyze the basic characteristics,drug features,prescription rules,and drug-symptom relationships of patients in the splenic deficiency and impairment stage,by data mining of medical records under the New Theory on Spleen Dampness Syndrome(Pi Dan Xin Lun,《脾瘅新论》).Methods Medical records listed in the“New Theory on Spleen Dampness Syndrome-Under-standing and Treatment of Metabolic Syndrome from the Perspective of Traditional Chinese Medicine”,and which were diagnosed with the spleen dampness syndrome at the splenic de-ficiency and impairment stage,during January 2004 and December 2016 were selected.These patients’data,including basic information,clinical symptoms,laboratory examination res-ults,traditional Chinese medicine(TCM)and western medicine diagnoses,treatment meth-ods,prescriptions,etc.,were collected.The collected data were subsequently compiled into a medical record database using the Epidata 3.1 data management software,followed by the use of Apriori algorithm provided in the SPSS Modeler 14.2 statistical software to investigate the association rules between drug-drug,drug-symptom,and drug-western medicine indices.Results(i)A total of 51 medical records were included,involving 17 types of syndromes.Among them,the top three with frequency≥3 included“Phlegm and blood stasis,and thoracic obstruction”“Deficiency-weakness of the spleen Qi,and static blood blocking collat-erals”,and“Deficiency-weakness of the spleen Qi,and static blood blocking collaterals”.Al-ternatively,of the 14 treatment methods,the top three treatments with frequency of≥3 in-cluded“Activating Yang and eliminating turbidity,and removing phlegm and dredging chan-nel blockage”“Strengthening the spleen and benefiting Qi,and eliminating phlegm to activ-ate the channels”,and“Warming Yang and benefiting Qi,and expelling cold to remove ob-structions”.Among the 15 prescriptions,the top three used with frequency≥3 included Huangqi Guizhi Wuwu Tang(黄芪桂枝五物汤),Gualou Xiebai Banxia Tang(瓜蒌薤白半夏汤),and Ganjiang Huangqin Huanglian Renshen Tang(干姜黄芩黄连人参汤).Lastly,of the 83 drugs used for a total of 476 times,those with frequency≥15 included Huanglian(Coptid-is Rhizoma),Huangqi(Astragali Radix),Jiudahuang(Wine-processed Rhei Radix et Rhizoma),Jixueteng(Spatholobi Caulis),Shengjiang(Zingiberis Rhizoma Recens),Huangqin(Scutellariae Radix),and Guizhi(Cinnamomi Ramulus).(ii)For the drug-drug associations,under the criteria of support≥15%and confidence=100%,seven second-order association rules,seven third-order rules,and six fourth-order roles were identified.The top-ranking rule of each was“Huangqin(Scutellariae Radix)→Huanglian(Coptidis Rhizoma)”“Ganjiang(Zingiberis Rhizoma)+Huangqin(Scutellariae Radix)→Huanglian(Coptidis Rhizoma)”,and“Baishao(Paeoniae Radix Alba)+Guizhi(Cinnamomi Ramulus)+Jixueteng(Spatho-lobi Caulis)→Huangqin(Scutellariae Radix)”,respectively.Alternatively,the drug-symptom associations were analyzed under the criteria of support≥5%and confidence=100%,which derived eight second-order association rules,31 third-order rules,and 30 fourth-order rules.The top-ranking association rule of each order was“Huangqi(Astragali Radix)→Limb ed-ema”“Guizhi(Cinnamomi Ramulus)+Jixueteng(Spatholobi Caulis)→Limb numbness and pain”,and“Guizhi(Cinnamomi Ramulus)+Jixueteng(Spatholobi Caulis)+Huangqi(As-tragali Radix)→Limb numbness and pain”,respectively.Similarly,the drug-western medi-cine index associations were investigated under the criteria of support≥5%and confidence=100%,and five second-order association rules,16 third-order rules,and 16 fourth-order rules were identified.In this category,the top-ranking association rule of each order was“Qinpi(Fraxini Cortex)→Uric acid”“Huanglian(Coptidis Rhizoma)+Ganjiang(Zingiberis Rhizoma)→Glycated hemoglobin”,and“Huanglian(Coptidis Rhizoma)+Ganjiang(Zing-iberis Rhizoma)+Huangqin(Scutellariae Radix)→Glycated hemoglobin”,respectively.Conclusion Through association rule mining,this study objectively and quantitatively demonstrated the drug-drug,drug-symptom,and drug-physicochemical index associations of patients with the spleen dampness syndrome at the splenic deficiency and impairment stage treated by Academician TONG Xiaolin.The results indicated that treatment for these patients adopted the“state-target”syndrome differentiation method.The drug combination was characterized by“small prescriptions”,targeting both the patient’s symptoms and signs(syndrome target)and western medicine indices(treatment target).This study could provide references for future research on the academic thoughts and medical experience of Academi-cian TONG Xiaolin.