基于复杂网络与互信息的聂莉芳教授治疗原发性肾病综合征经验研究
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摘要
原发性肾病综合征(PNS)为临床常见疑难病,其病程迁延,呈进行性发展,部分患者逐渐发展为肾衰竭,严重影响患者的生存质量,给患者和社会带来了极大的痛苦和负担。西医使用激素及免疫抑制剂治疗,但副作用较大,同时部分患者呈现对激素的反抗性而无效。中医药治疗有一定的优势与特色,部分患者单纯运用中药即可控制病情。对于在外院已用激素的患者,一方面可以协同提高疗效,另一方面可以顺利地撤减激素,并且减轻激素的副作用。本研究通过临床资料的回顾性分析和运用数据挖掘中的互信息和复杂网络分析,旨在总结导师治疗PNS的学术思想和临证经验,为进一步规范中医辨证论治、提高临床疗效提供可靠依据。
原发性肾病综合征的现代医学研究
通过西医文献的研究,阐述了原发性肾病综合征的概述、发病机制(细胞免疫及体液免疫机制、水肿机制)、治疗(水肿的治疗、免疫抑制剂及其他治疗)等方面的研究进展。
国内著名中医诊治经验概述
通过对文献的整理和分析,总结了多位中医名家的经验,从病名、病因病机、诊断及辨证、治疗、调养等几方面进行概述。肾病综合征归属于中医学“水肿”等范畴,属本虚标实、虚实夹杂之病,脾肾虚损是病机关键,湿、瘀是主要邪气,感染是加重、复发的重要因素,其治疗则是从不同的角度切入而施以辨证论治。
聂莉芳教授治疗原发性肾病综合征经验概述
治疗思路与程序：能中不西,先中后西,运用中药,减撤西药；先治水肿,后治蛋白尿；分阶段治疗。
治疗经验：(1)分阶段论治：水肿突出阶段,注重调理脾胃,降逆止呕,健脾利水,协调水、气、血的关系,配合食疗法。蛋白尿持续阶段：健脾益气以升清,益气滋肾以固精。大量激素使用阶段、激素撤减阶段：配合中医药辨证治疗。(2)分型论治：分气虚水停、阳虚水停、阴虚水停、气滞水停、湿热内蕴、血瘀水停论治。
病例一般特征
病例来自中国中医科学院西苑医院肾内科2007年1月～2012年1月病房住院期间经导师诊治及导师专家门诊诊治的PNS患者,共161例,410诊次。男女比例1.875：1。其中膜性肾病22例,微小病变10例,系膜增生12例,系膜毛细血管1例,局灶节段性肾小球硬化3例,未行肾活检113例。
中医证候分析
本研究纳入病例出现频数为20%以上的症状依次为：神疲乏力、蛋白尿、双下肢水肿、舌淡暗、腰膝酸软、头晕、纳差、眠差、便秘、苔薄黄、舌红、咽痛、咳嗽、舌有瘀斑、脉沉涩、脉细数、心悸、腹胀。中医辨证分型,气阴两虚最为多见(30.05%),其次为血瘀水停(20.73%),阴虚火旺(15.61%),脾胃虚弱(11.95%),气滞水停(8.54%)。
聂莉芳教授治疗经验挖掘
本研究纳入病例使用频数为10%以上的方剂依次为：当归芍药散(23.41%)、参芪地黄汤(18.54%)、香砂六君子汤(12.44%)、知柏地黄汤(11.95%)、五皮饮(10.24%)。使用频数为50%以上的中药为：茯苓(89.51%)、芡实(82.44%)、生黄芪(79.76%)、金银花(78.05%)、丹参(70%)、太子参(66.1%)、冬瓜皮(65.37)、泽泻(57.8%)、白术(51.95%)。
根据互信息、复杂网络分析,总结导师治疗本病经验
(1)扶正祛邪,标本兼顾,缓则治本,急则治标。益气养阴为最常用的治法。(2)脾肾为本,整体调治。治肾,常以六味地黄汤加减灵活应用,注重调理脾胃。(3)重视活血利水。擅用当归芍药散。(4)方证相应,抓主症选方,但见一症便是,不必悉具,可大大提高临床诊治效率和准确度。(5)随症加减用药,用药平和,轻清灵动,既避免大辛大热伤津耗液,亦避免大苦大寒伤脾败胃,务以临床实效为是。(6)处方立法灵活,用药配伍精妙,重视气、血、阴、阳之间的关系,补中有通,补泻结合,补而不滞。
创新点：1.首次运用中医复杂分析系统数据挖掘软件,对证型-方剂、症状-方剂、症状-中药,进行互信息相关分析方法,从大量的、模糊的数据中集中挖掘导师聂莉芳教授治疗肾病综合征的处方用药规律。
2.运用中医复杂分析系统数据挖掘软件,首次对主要证型所用中药进行复杂网络分析,从大量的、模糊的数据中集中总结导师聂莉芳教授治疗肾病综合征的经验。
Primary nephrotic syndrome (PNS) is a kind of common clinical difficult disease. It has a lingering course and some patients develop to renal failure gradually. So it seriously affects the quality of life of patients and has brought great pain and burden to patients and society. Western medicine use corticosteroids and immunosuppressive to treat, but with serious side effects, while some patients presenting for corticosteroids resistance and invalid. However Traditional Chinese Medicine (TCM) has certain advantages and characteristics, some patients only using Chinese herbs can control illness. On one hand, TCM can collaborate to improve efficacy. On the other hand, it can help to withdrawal of corticosteroids and reduce the side effects of corticosteroids. By retrospective analysis of clinical data, this study applies data mining such as mutual information and complex network analysis to conclude my supervisor's academic idea and clinical experience of treatment of NS. It will provide a reliable basis to further standardize the TCM diagnosis and treatment and improve the clinical efficacy.
Modern Medical Research of Nephrotic Syndrome
By overview of Western medicine literature, it elaborates the research progress of the outline, pathogenesis (cellular immunity and humoral immune mechanisms, edema mechanism), treatment (edema, immunosuppressive agents and other treatment) of the nephrotic syndrome.
Overview of Professor Nie Lifang's Experience of Diagnosis and Treatment of TCM
Through the collation and analysis of the literature, the experience of modern TCM masters is summarized and overviewed from such areas as the name of disease, etiology and pathogenesis, diagnosis and syndrome differentiation, treatment and recuperation. NS attributes to "Edema" and other areas in TCM. It is rooted defficiency-symptomed excess and mixed with defficiency and excess. Deficiency of spleen and kidney is the pathogenesis, dampness. Blood stasis is the main evil. Infection is an important factor of deterioration and recurrence. The treatment principle is differential treatment from different points of view.
Outline of The Treatment Experience of Professor Nie Lifang
Treatment ideas and procedures:choosing rather Chinese medicine than western medicine, choosing Chinese medicine first, then western medicine, using Chinese medicine, withdrawaling western medicine; treating edema first, then proteinuria; treatment varies in different stage.
Treatment experience:(1) Treatment in different stage:In prominent Edema stage, it should be payed attention to regulating spieen and stomach, strengthening spleen to induce diuresis, coordinating relationship of qi, blood and water and with diet therapy. In continuous proteinuria stage, it is important to invigorate spleen and replenish qi to send up essential substance, enrich qi and nourish Kidney to secure essence. In large steroid using stage and steroid withdrawal phase, differential treatment of TCM should be accompanied.(2) Treatment in different syndrom type: treatment should be given according to qi deficiency and dropsy, yang deficiency and dropsy, yin deficiency and dropsy, qi stagnation and dropsy, retention of damp-heat and blood stasis and dropsy.
General Characteristics of Cases
The cases are NS patients diagnosed and treated by my supervisor during January,2007to January2012, a total of161cases,410clinic times. The ratio of male to female is1.875:1. Among them,10cases of minimal change disease,12cases of mesangial proliferation,1case of mesangiocapillary glomerulonephritis,3cases of focal segmental glomerulus sclerosis and22cases of membranous nephropathy,113cases without renal biopsy.
Analysis of TCM Syndrome
The symptoms of which the frequency is more than20%in this study are in order: spiritlessness and fatigue, proteinuria, lower extremity edema, pale dark tongue, listless of waist and knees, dizziness, anorexia, constipation, yellow thin fur, reddened tongue, sore throat, cough, ecchymosis on the tongue, sunken and astringent pulse, thin and rapid pulse, palpitations and abdominal distension. TCM syndrome types, dual deficiency of qi and yin is the most common in the main syndrome (57.76%), followed by blood stasis and dropsy (20.73%), dficiency of spleen and stomach (11.95%), qi stagnation and dropsy (8.54%).
Mining of The Treatment Experience of Professor Nie Lifang
The prescriptions of which the frequency is more than10%in this study are in order:Dangguishaoyao powder (23.41%), Shenqidihuang decoction (18.54%), Xiangshaliujunzi decoction (12.44%), Zhibaidihuang decoction (11.95%), Wupi drink (10.24%). The herb of which the frequency is more than50%is as follows: Poria (Fuling)(89.51%), Euryale Ferox (Qianshi)(82.44%), Radix Astragali Seu Hedysari (Shenghuangqi)(79.76%), Flos Lonicerae (Jinyinhua)(78.05%), Radix Salviae Miltiorrhizae (Danshen)(70%), Radix Pesudostellariae (Taizishen)(66.1%), White Gourd Peel (Dongguapi)(65.37%), Rnizoma Alismatis (Zexie)(57.8%), Atractylodes Macrocephala (51.95%).
By mutual information and complex network analysis, I concluded the experience of my supervisor in treating NS as follows:(1) Syndrome differentiation and treatment in different phase, the main treatment in chronic deferral phase (deficiency stage) to strenthen the root vital qi. Strenthening qi and tonifying yin is the most common method.(2) With spleen and kidney as the root, the treatment is overall. To treat kidney, modified Liuwei Dihuang decoction is commonly used. Regulation of spleen and stomach is payed attention to.(3) The method of activating blood and promoting diuresis is payed attention to and Dangguishaoyao powder is often used.(4) Correspondence of syndrome and prescription. Select formula through grasping the main symptoms. One typical symptom is enough for symptom differentiation which can greatly improve the efficiency and accuracy of clinical diagnosis and treatment.(5) Herb modification with symptoms, calm, light and agile, which avoids too hot and fragrant to damage fluid and too bitter and cold to hurt spleen and stomach, all for the clinical effect.(6) Agile method and prescription, exquisite herb compatibility.Relationship between qi, blood, yin and yang is payed attention to. Tonifying is combined with dredging and eliminating the pathogen, with no stagnation.
By the use of mutual information and complex network to analyze the law of syndrome differenciation and prescription of my supervisor will help to find the law of clinical treatment and to promote effective herbs. That will help to conclude the experience of old famous TCM doctors further scientificly and systematicly, then to inherit and carry forward.
Innovation:1. For the first time by the use of traditional Chinese medicine complex analysis system data mining software, syndrome-prescription, symptoms, symptom-traditional Chinese medicine prescription for mutual information, correlation analysis method, from the massive, fuzzy data mining mentor professor Nie Lifang treatment of nephrotic syndrome in the prescription drug law.2. By the use of traditional Chinese medicine complex analysis system data mining software, for the first time on the main syndromes of traditional Chinese medicine used in complex network analysis, from the massive, fuzzy data summary of tutor Professor Nie Lifang treatment of nephrotic syndrome experience.
原发性肾病综合征的现代医学研究
通过西医文献的研究,阐述了原发性肾病综合征的概述、发病机制(细胞免疫及体液免疫机制、水肿机制)、治疗(水肿的治疗、免疫抑制剂及其他治疗)等方面的研究进展。
国内著名中医诊治经验概述
通过对文献的整理和分析,总结了多位中医名家的经验,从病名、病因病机、诊断及辨证、治疗、调养等几方面进行概述。肾病综合征归属于中医学“水肿”等范畴,属本虚标实、虚实夹杂之病,脾肾虚损是病机关键,湿、瘀是主要邪气,感染是加重、复发的重要因素,其治疗则是从不同的角度切入而施以辨证论治。
聂莉芳教授治疗原发性肾病综合征经验概述
治疗思路与程序：能中不西,先中后西,运用中药,减撤西药；先治水肿,后治蛋白尿；分阶段治疗。
治疗经验：(1)分阶段论治：水肿突出阶段,注重调理脾胃,降逆止呕,健脾利水,协调水、气、血的关系,配合食疗法。蛋白尿持续阶段：健脾益气以升清,益气滋肾以固精。大量激素使用阶段、激素撤减阶段：配合中医药辨证治疗。(2)分型论治：分气虚水停、阳虚水停、阴虚水停、气滞水停、湿热内蕴、血瘀水停论治。
病例一般特征
病例来自中国中医科学院西苑医院肾内科2007年1月～2012年1月病房住院期间经导师诊治及导师专家门诊诊治的PNS患者,共161例,410诊次。男女比例1.875：1。其中膜性肾病22例,微小病变10例,系膜增生12例,系膜毛细血管1例,局灶节段性肾小球硬化3例,未行肾活检113例。
中医证候分析
本研究纳入病例出现频数为20%以上的症状依次为：神疲乏力、蛋白尿、双下肢水肿、舌淡暗、腰膝酸软、头晕、纳差、眠差、便秘、苔薄黄、舌红、咽痛、咳嗽、舌有瘀斑、脉沉涩、脉细数、心悸、腹胀。中医辨证分型,气阴两虚最为多见(30.05%),其次为血瘀水停(20.73%),阴虚火旺(15.61%),脾胃虚弱(11.95%),气滞水停(8.54%)。
聂莉芳教授治疗经验挖掘
本研究纳入病例使用频数为10%以上的方剂依次为：当归芍药散(23.41%)、参芪地黄汤(18.54%)、香砂六君子汤(12.44%)、知柏地黄汤(11.95%)、五皮饮(10.24%)。使用频数为50%以上的中药为：茯苓(89.51%)、芡实(82.44%)、生黄芪(79.76%)、金银花(78.05%)、丹参(70%)、太子参(66.1%)、冬瓜皮(65.37)、泽泻(57.8%)、白术(51.95%)。
根据互信息、复杂网络分析,总结导师治疗本病经验
(1)扶正祛邪,标本兼顾,缓则治本,急则治标。益气养阴为最常用的治法。(2)脾肾为本,整体调治。治肾,常以六味地黄汤加减灵活应用,注重调理脾胃。(3)重视活血利水。擅用当归芍药散。(4)方证相应,抓主症选方,但见一症便是,不必悉具,可大大提高临床诊治效率和准确度。(5)随症加减用药,用药平和,轻清灵动,既避免大辛大热伤津耗液,亦避免大苦大寒伤脾败胃,务以临床实效为是。(6)处方立法灵活,用药配伍精妙,重视气、血、阴、阳之间的关系,补中有通,补泻结合,补而不滞。
创新点：1.首次运用中医复杂分析系统数据挖掘软件,对证型-方剂、症状-方剂、症状-中药,进行互信息相关分析方法,从大量的、模糊的数据中集中挖掘导师聂莉芳教授治疗肾病综合征的处方用药规律。
2.运用中医复杂分析系统数据挖掘软件,首次对主要证型所用中药进行复杂网络分析,从大量的、模糊的数据中集中总结导师聂莉芳教授治疗肾病综合征的经验。
Primary nephrotic syndrome (PNS) is a kind of common clinical difficult disease. It has a lingering course and some patients develop to renal failure gradually. So it seriously affects the quality of life of patients and has brought great pain and burden to patients and society. Western medicine use corticosteroids and immunosuppressive to treat, but with serious side effects, while some patients presenting for corticosteroids resistance and invalid. However Traditional Chinese Medicine (TCM) has certain advantages and characteristics, some patients only using Chinese herbs can control illness. On one hand, TCM can collaborate to improve efficacy. On the other hand, it can help to withdrawal of corticosteroids and reduce the side effects of corticosteroids. By retrospective analysis of clinical data, this study applies data mining such as mutual information and complex network analysis to conclude my supervisor's academic idea and clinical experience of treatment of NS. It will provide a reliable basis to further standardize the TCM diagnosis and treatment and improve the clinical efficacy.
Modern Medical Research of Nephrotic Syndrome
By overview of Western medicine literature, it elaborates the research progress of the outline, pathogenesis (cellular immunity and humoral immune mechanisms, edema mechanism), treatment (edema, immunosuppressive agents and other treatment) of the nephrotic syndrome.
Overview of Professor Nie Lifang's Experience of Diagnosis and Treatment of TCM
Through the collation and analysis of the literature, the experience of modern TCM masters is summarized and overviewed from such areas as the name of disease, etiology and pathogenesis, diagnosis and syndrome differentiation, treatment and recuperation. NS attributes to "Edema" and other areas in TCM. It is rooted defficiency-symptomed excess and mixed with defficiency and excess. Deficiency of spleen and kidney is the pathogenesis, dampness. Blood stasis is the main evil. Infection is an important factor of deterioration and recurrence. The treatment principle is differential treatment from different points of view.
Outline of The Treatment Experience of Professor Nie Lifang
Treatment ideas and procedures:choosing rather Chinese medicine than western medicine, choosing Chinese medicine first, then western medicine, using Chinese medicine, withdrawaling western medicine; treating edema first, then proteinuria; treatment varies in different stage.
Treatment experience:(1) Treatment in different stage:In prominent Edema stage, it should be payed attention to regulating spieen and stomach, strengthening spleen to induce diuresis, coordinating relationship of qi, blood and water and with diet therapy. In continuous proteinuria stage, it is important to invigorate spleen and replenish qi to send up essential substance, enrich qi and nourish Kidney to secure essence. In large steroid using stage and steroid withdrawal phase, differential treatment of TCM should be accompanied.(2) Treatment in different syndrom type: treatment should be given according to qi deficiency and dropsy, yang deficiency and dropsy, yin deficiency and dropsy, qi stagnation and dropsy, retention of damp-heat and blood stasis and dropsy.
General Characteristics of Cases
The cases are NS patients diagnosed and treated by my supervisor during January,2007to January2012, a total of161cases,410clinic times. The ratio of male to female is1.875:1. Among them,10cases of minimal change disease,12cases of mesangial proliferation,1case of mesangiocapillary glomerulonephritis,3cases of focal segmental glomerulus sclerosis and22cases of membranous nephropathy,113cases without renal biopsy.
Analysis of TCM Syndrome
The symptoms of which the frequency is more than20%in this study are in order: spiritlessness and fatigue, proteinuria, lower extremity edema, pale dark tongue, listless of waist and knees, dizziness, anorexia, constipation, yellow thin fur, reddened tongue, sore throat, cough, ecchymosis on the tongue, sunken and astringent pulse, thin and rapid pulse, palpitations and abdominal distension. TCM syndrome types, dual deficiency of qi and yin is the most common in the main syndrome (57.76%), followed by blood stasis and dropsy (20.73%), dficiency of spleen and stomach (11.95%), qi stagnation and dropsy (8.54%).
Mining of The Treatment Experience of Professor Nie Lifang
The prescriptions of which the frequency is more than10%in this study are in order:Dangguishaoyao powder (23.41%), Shenqidihuang decoction (18.54%), Xiangshaliujunzi decoction (12.44%), Zhibaidihuang decoction (11.95%), Wupi drink (10.24%). The herb of which the frequency is more than50%is as follows: Poria (Fuling)(89.51%), Euryale Ferox (Qianshi)(82.44%), Radix Astragali Seu Hedysari (Shenghuangqi)(79.76%), Flos Lonicerae (Jinyinhua)(78.05%), Radix Salviae Miltiorrhizae (Danshen)(70%), Radix Pesudostellariae (Taizishen)(66.1%), White Gourd Peel (Dongguapi)(65.37%), Rnizoma Alismatis (Zexie)(57.8%), Atractylodes Macrocephala (51.95%).
By mutual information and complex network analysis, I concluded the experience of my supervisor in treating NS as follows:(1) Syndrome differentiation and treatment in different phase, the main treatment in chronic deferral phase (deficiency stage) to strenthen the root vital qi. Strenthening qi and tonifying yin is the most common method.(2) With spleen and kidney as the root, the treatment is overall. To treat kidney, modified Liuwei Dihuang decoction is commonly used. Regulation of spleen and stomach is payed attention to.(3) The method of activating blood and promoting diuresis is payed attention to and Dangguishaoyao powder is often used.(4) Correspondence of syndrome and prescription. Select formula through grasping the main symptoms. One typical symptom is enough for symptom differentiation which can greatly improve the efficiency and accuracy of clinical diagnosis and treatment.(5) Herb modification with symptoms, calm, light and agile, which avoids too hot and fragrant to damage fluid and too bitter and cold to hurt spleen and stomach, all for the clinical effect.(6) Agile method and prescription, exquisite herb compatibility.Relationship between qi, blood, yin and yang is payed attention to. Tonifying is combined with dredging and eliminating the pathogen, with no stagnation.
By the use of mutual information and complex network to analyze the law of syndrome differenciation and prescription of my supervisor will help to find the law of clinical treatment and to promote effective herbs. That will help to conclude the experience of old famous TCM doctors further scientificly and systematicly, then to inherit and carry forward.
Innovation:1. For the first time by the use of traditional Chinese medicine complex analysis system data mining software, syndrome-prescription, symptoms, symptom-traditional Chinese medicine prescription for mutual information, correlation analysis method, from the massive, fuzzy data mining mentor professor Nie Lifang treatment of nephrotic syndrome in the prescription drug law.2. By the use of traditional Chinese medicine complex analysis system data mining software, for the first time on the main syndromes of traditional Chinese medicine used in complex network analysis, from the massive, fuzzy data summary of tutor Professor Nie Lifang treatment of nephrotic syndrome experience.
引文
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