类风湿关节炎治疗方案研究
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摘要
一、背景
类风湿性关节炎(RA)是一种以关节的慢性炎症为主要表现的自身免疫性疾病,是临床多发病、疑难病,致残率较高。西医强调尽早使用控制疾病的抗风湿药和联合用药,以控制或延缓病情的发展,防止骨质破坏,但由于至今尚未发现真正的能控制疾病发展的药物,加上西药严重的毒副作用,致使RA的治疗十分棘手。RA属于中医痹病中的旭痹,中医治疗痹病具有疗法众多、疗效肯定、毒副作用少的特点,已显示出一定的优势。但由于中医药治疗RA的临床研究存在着不少问题,导致研究结论的真实性和可重复性受到影响,难以科学、客观地评价中医药治疗RA的疗效,也远不能反映出中医治疗RA的优势。随着中医药临床研究水平的不断提高,以及临床流行病学/DME方法在中医药领域中的广泛应用和我国GCP规范的实施,迫切需要将中医药对RA己显示出较好临床疗效的治疗方案进行更深入的研究,探讨中医药治疗RA的能体现中医优势的优化方案,不仅有利于提高中医药治疗RA的临床水平,使之能被国际医药界所接受,而且对于中医药临床研究水平的提高具有普遍的指导意义。
二、目的
本课题根据尪痹病证特点,采用辨病+辨证相结合的综合治疗方案,通过多中心、随机对照临床试验和盲法评价的方法,与国内外公认的、经典的西医综合治疗方案进行对比,采用国际公认的疗效判断标准(ACR-20),引用HAQ量表进行患者生活质量的评价,结合中医证候疗效评价及骨质变化等指标,对中医综合治疗方案进行观察和评价,为提高类风湿关节炎这一难治性疾病的临床疗效进行了有益的探索,弥补当前类风湿关节炎治疗中的不足,规范类风湿关节炎的中医治疗方案,提高类风湿关节炎的中医治疗水平,以期能在全国推广和应用,并能使国际医药界所接受。
三、方法
本研究为多中心、随机对照的临床试验,来自全国九个研究单位的522例患者被纳入研究,病例分组采用各中心控制的简单随机化方法,研究中采用了单盲与第三者评价的方法。治疗组为中医综合治疗方案,即在使用雷公藤多甙片、益肾蠲痹丸治疗的基础上,根据中医证型的不同分别加用寒湿痹颗粒、湿热痹颗粒、寒热痹颗粒和尫痹颗粒;对照组为西医综合治疗方案,即非甾体抗炎药扶他林缓释片加慢作用药甲氨喋呤、柳氮磺胺吡啶。观察疗程为半年。本研究对方案依从性较好的329例活动期病例进行了有效性观察,对所有接受治疗病例510例(505例+5例)进行了安全性观察。有效性观察包括主要疗效指标:ACR-20、X线改变、中医证候疗效;次要疗效指标:症状/体征、主观指标、实验室指标、生存质量HAQ量表等,并进行了多中心效应分析、分层分析等。安全性观察主要包括不良事件及实验室指标异常的分析。
Background:Rheumatoid Arthritis (RA) is one sort of autoimmunity disease manifested as chronic arthral inflammation with high disabled ratio. In order to control aggravation of the disease and avert the damage of bone joints, Western medicine emphasizes the use of anti-rheumatism drugs and the combined use with other drugs. Unfortunately, up to the present, there is no ideal drug to be able to satisfactorily control the development of the disease. And to make things worse, the western medical drugs are full of side effects, so the therapy of RA is very intractability. According to the traditional Chinese Medicine (TCM) RA belongs to the diseases of Wang-bi. Compared with treatment with west medicine, TCM has some advantages in treatment of RA, which are characterized as multiple therapeutics, affirmative curative effects and fewer side effects.Since there exist in the clinical research of the TCM on RA a lot of questions which influences the validity and reliability of the studies and so it is hard to precisely evaluate the curative effect of the TCM and manifest its advantages. With the improvement of clinic research, and the wide-spread apply of Clinical Epidemiology Measure/DME in TCM and GCP normative put in practice in our country, It is urgently needed to have further studies on those TCM treatment prescription which have showed pretty good clinical therapeutic effects, in order to find out the better treatment plans which can manifest the advantages of TCM. So these studies are good not only to improve the treating level of TCM on RA, which would be accepted by the medical world, but also to have the general directing meaning to improve clinical research of TCM.Objective:Based on characteristics of the wangbi, the study, adopting the integration treatment plans of disease oriented and symptom oriented
diagnosis of TCM, and via the means of polycentric and random comparison clinic experimentation and blind evaluate, contrasting with classical and accepted western integration project, using the standard curative effect estimate criterion (ACR-20), quoting HAQ measuring scale to evaluate patient' s life quality , uniting the guidelines of the evaluation of the curative effect of TCM and osseous change, observed and evaluated the TCM treatment plans, so as to improve the clinic curative effect on RA, which is still a refractory disease. It would also make up the shortage of RA therapy at present, make a norm for TCM treatment plans and improve therapeutic levels of RA. Hopefully the treatment would be nationally spread and applied, and internationally accepted.Method:The study was a clinic test of multi-center and random contrast, 522 patients coming from 9 study units in the country were grouped by simple randomization methods. During the course of study single blind and independence evaluations were adopted. The reatment group was TCM treatment plan, namely based on the use of tripterygium glycosides , YISHENJUANBIWAN, and the treatment varied according to different types of symptom, so there were such different treatment plans as Hanshibi granule, Shirebi granule, hanrebi granule and wangbi granule; contrast group was western medical integration therapy, namely NSAID diclofenac sodium sustained release tablets, DMARD- MTX and SASP. The period of treatment was half a year. The studies observed 329 activity cases that had good compliance with the research project, surveyed the security of 510 cases (505+5) that received therapy. Validity observation included the main index of the curative effect: ACR-20, X-ray, the therapeutic effect on symptom of TCM; the secondary index: symptom/body signs, subjective index, laboratory index, survival quality HAQ measure scale and so on. At the same time multi-center domino effect analysis, delamination analysis and so on were undertaken. Security observations mostly included bad events and analysis of the laboratory abnormal indexes.Result:1. Analysis of the main curative effect index :ACR improvement rate between treatment and contrast groups: by means of PP method the results showed that the difference is not of statistics significance (P>0. 05) between two groups after 12weeks and 24weeks. By ITT
means the difference had no significance (P>0. 05) after 24weeks.X-ray improvement rate between two groups: compared with before, X-ray grading difference was statistically of significance ( Z=-2. 11, p=0. 04) after 24 weeks , TCM group excelled western medical group in X-ray improvement.The comparison of the curative effect of TCM symptoms: there was not of statistics significance in the availability rate between the two groups after 12 、 24weeks (P >0. 05). There was also not of statistics significance at any time according to inefficacy ,availability, apparent effect, clinic heal (P >0.05) .2. Analysis of the secondary curative effect index:(1) Symptom/sign (rest pain, tenderness count, tenderness index, swollen count, swollen index, morning numb, mean grasp force of two hands and walking time of 20 meters):Every time point after treatment was compared with baseline, the result showed: difference of tenderness count in 2 weeks, mean grasp force of two hands in 2, 4 weeks, walking time of 20 meters in 2, 4 weeks with baseline had no significance(P>0. 05). Other indexes at each time point was better compared with baseline. The difference had statistics significance (P<0. 01 或 P<0. 05) .The two groups were compared after treatment, and the results showed: the difference on rest pain had statistics significance in 2、 16and 24weeks(P<0. 05). The western medical group was superior to TCM group. At other time points, no change of other indexes could be found.(2) Subjective index analysis (evaluation coming from patients, doctors) ① Compared with baseline at the every time point after treatment:both the indexes were improved, the difference of which was of statistics significance (P<0. 01);② The change between two groups between the time points after treatment: the difference had no statistics significance (P>0. 05) .(3) Laboratory index analysis (ESR、 CRP 、 RF 、 IgA 、 IgG 及 IgM)① Compared with baseline: after 12 weeks , ESR、 IgA and IgG had someimprovement in the TCM group, and the difference had statistics significance(P<0.01, P<0. 05); after 24 weeks, ESR、 CRP、 RF 、 IgA 、 IgG and IgM wereall improved, the difference of which were of statistics significance (P<0. 01,P<0. 05); compared with baseline, after 12、 24 weeks, the indexes of the western
medical group were decreased, and the difference had statistics significance (P<0.01, P<0.05) .(2) Compared with two groups after treatment: for RF after 12 weeks and ESR after 24 weeks, the decrease in the western medical group excelled that of the TCM group, the difference had statistics significance (P<0. 01, P<0. 05), other difference had no statistics significance (P>0. 05) . (4) Living quality HAQ analysis① Comparison between mean HAQ of the two groups with baseline: after 12、 24 weeks, HAQ score was improved, and the difference had statistics significance (P<0.01, P<0. 05) .② HAQ mean value between two groups after therapy: the difference had no statistics significance between each week (P>0.05), which meant similar improvement of HAQ in the two groups. 3. Security analysisIn the respect of security, bad events and the abnormality of laboratory index were analyzed. The results were mainly manifested as followings:(1) With the exception of the similarity in the abnormal reaction frequency of alimentary canal symptonu kidney function and abnormal menstruation among the three groups, the frequency of the blood system , liver damage and other abnormal reactions in the TCM group was lower than that of the western medical group.(2) In the respects of the person—time of abnormal liver function that first set in and the degree of abnormality, the TCM group was lower to the other two groups.(3) Considering the patient number of abnormal menstruation that first set in every week, in 2, 4> 12week the TCM group was slightly lower than the western medical group, while the TCM group was a little higher than the western medical group in other weeks.Concluusion:TCM integration plan could effectively inhibit the inflammation, and the effect was similar to that of generally accepted western medicine therapy, the effects of which were manifested as improving joint functions, reducing the pain and swelling, promoting life quality. And what' s more, TCM treatment had some potential value in the respect of delaying the development of RA.In the respects of improving and controlling the inflammation, the
类风湿性关节炎(RA)是一种以关节的慢性炎症为主要表现的自身免疫性疾病,是临床多发病、疑难病,致残率较高。西医强调尽早使用控制疾病的抗风湿药和联合用药,以控制或延缓病情的发展,防止骨质破坏,但由于至今尚未发现真正的能控制疾病发展的药物,加上西药严重的毒副作用,致使RA的治疗十分棘手。RA属于中医痹病中的旭痹,中医治疗痹病具有疗法众多、疗效肯定、毒副作用少的特点,已显示出一定的优势。但由于中医药治疗RA的临床研究存在着不少问题,导致研究结论的真实性和可重复性受到影响,难以科学、客观地评价中医药治疗RA的疗效,也远不能反映出中医治疗RA的优势。随着中医药临床研究水平的不断提高,以及临床流行病学/DME方法在中医药领域中的广泛应用和我国GCP规范的实施,迫切需要将中医药对RA己显示出较好临床疗效的治疗方案进行更深入的研究,探讨中医药治疗RA的能体现中医优势的优化方案,不仅有利于提高中医药治疗RA的临床水平,使之能被国际医药界所接受,而且对于中医药临床研究水平的提高具有普遍的指导意义。
二、目的
本课题根据尪痹病证特点,采用辨病+辨证相结合的综合治疗方案,通过多中心、随机对照临床试验和盲法评价的方法,与国内外公认的、经典的西医综合治疗方案进行对比,采用国际公认的疗效判断标准(ACR-20),引用HAQ量表进行患者生活质量的评价,结合中医证候疗效评价及骨质变化等指标,对中医综合治疗方案进行观察和评价,为提高类风湿关节炎这一难治性疾病的临床疗效进行了有益的探索,弥补当前类风湿关节炎治疗中的不足,规范类风湿关节炎的中医治疗方案,提高类风湿关节炎的中医治疗水平,以期能在全国推广和应用,并能使国际医药界所接受。
三、方法
本研究为多中心、随机对照的临床试验,来自全国九个研究单位的522例患者被纳入研究,病例分组采用各中心控制的简单随机化方法,研究中采用了单盲与第三者评价的方法。治疗组为中医综合治疗方案,即在使用雷公藤多甙片、益肾蠲痹丸治疗的基础上,根据中医证型的不同分别加用寒湿痹颗粒、湿热痹颗粒、寒热痹颗粒和尫痹颗粒;对照组为西医综合治疗方案,即非甾体抗炎药扶他林缓释片加慢作用药甲氨喋呤、柳氮磺胺吡啶。观察疗程为半年。本研究对方案依从性较好的329例活动期病例进行了有效性观察,对所有接受治疗病例510例(505例+5例)进行了安全性观察。有效性观察包括主要疗效指标:ACR-20、X线改变、中医证候疗效;次要疗效指标:症状/体征、主观指标、实验室指标、生存质量HAQ量表等,并进行了多中心效应分析、分层分析等。安全性观察主要包括不良事件及实验室指标异常的分析。
Background:Rheumatoid Arthritis (RA) is one sort of autoimmunity disease manifested as chronic arthral inflammation with high disabled ratio. In order to control aggravation of the disease and avert the damage of bone joints, Western medicine emphasizes the use of anti-rheumatism drugs and the combined use with other drugs. Unfortunately, up to the present, there is no ideal drug to be able to satisfactorily control the development of the disease. And to make things worse, the western medical drugs are full of side effects, so the therapy of RA is very intractability. According to the traditional Chinese Medicine (TCM) RA belongs to the diseases of Wang-bi. Compared with treatment with west medicine, TCM has some advantages in treatment of RA, which are characterized as multiple therapeutics, affirmative curative effects and fewer side effects.Since there exist in the clinical research of the TCM on RA a lot of questions which influences the validity and reliability of the studies and so it is hard to precisely evaluate the curative effect of the TCM and manifest its advantages. With the improvement of clinic research, and the wide-spread apply of Clinical Epidemiology Measure/DME in TCM and GCP normative put in practice in our country, It is urgently needed to have further studies on those TCM treatment prescription which have showed pretty good clinical therapeutic effects, in order to find out the better treatment plans which can manifest the advantages of TCM. So these studies are good not only to improve the treating level of TCM on RA, which would be accepted by the medical world, but also to have the general directing meaning to improve clinical research of TCM.Objective:Based on characteristics of the wangbi, the study, adopting the integration treatment plans of disease oriented and symptom oriented
diagnosis of TCM, and via the means of polycentric and random comparison clinic experimentation and blind evaluate, contrasting with classical and accepted western integration project, using the standard curative effect estimate criterion (ACR-20), quoting HAQ measuring scale to evaluate patient' s life quality , uniting the guidelines of the evaluation of the curative effect of TCM and osseous change, observed and evaluated the TCM treatment plans, so as to improve the clinic curative effect on RA, which is still a refractory disease. It would also make up the shortage of RA therapy at present, make a norm for TCM treatment plans and improve therapeutic levels of RA. Hopefully the treatment would be nationally spread and applied, and internationally accepted.Method:The study was a clinic test of multi-center and random contrast, 522 patients coming from 9 study units in the country were grouped by simple randomization methods. During the course of study single blind and independence evaluations were adopted. The reatment group was TCM treatment plan, namely based on the use of tripterygium glycosides , YISHENJUANBIWAN, and the treatment varied according to different types of symptom, so there were such different treatment plans as Hanshibi granule, Shirebi granule, hanrebi granule and wangbi granule; contrast group was western medical integration therapy, namely NSAID diclofenac sodium sustained release tablets, DMARD- MTX and SASP. The period of treatment was half a year. The studies observed 329 activity cases that had good compliance with the research project, surveyed the security of 510 cases (505+5) that received therapy. Validity observation included the main index of the curative effect: ACR-20, X-ray, the therapeutic effect on symptom of TCM; the secondary index: symptom/body signs, subjective index, laboratory index, survival quality HAQ measure scale and so on. At the same time multi-center domino effect analysis, delamination analysis and so on were undertaken. Security observations mostly included bad events and analysis of the laboratory abnormal indexes.Result:1. Analysis of the main curative effect index :ACR improvement rate between treatment and contrast groups: by means of PP method the results showed that the difference is not of statistics significance (P>0. 05) between two groups after 12weeks and 24weeks. By ITT
means the difference had no significance (P>0. 05) after 24weeks.X-ray improvement rate between two groups: compared with before, X-ray grading difference was statistically of significance ( Z=-2. 11, p=0. 04) after 24 weeks , TCM group excelled western medical group in X-ray improvement.The comparison of the curative effect of TCM symptoms: there was not of statistics significance in the availability rate between the two groups after 12 、 24weeks (P >0. 05). There was also not of statistics significance at any time according to inefficacy ,availability, apparent effect, clinic heal (P >0.05) .2. Analysis of the secondary curative effect index:(1) Symptom/sign (rest pain, tenderness count, tenderness index, swollen count, swollen index, morning numb, mean grasp force of two hands and walking time of 20 meters):Every time point after treatment was compared with baseline, the result showed: difference of tenderness count in 2 weeks, mean grasp force of two hands in 2, 4 weeks, walking time of 20 meters in 2, 4 weeks with baseline had no significance(P>0. 05). Other indexes at each time point was better compared with baseline. The difference had statistics significance (P<0. 01 或 P<0. 05) .The two groups were compared after treatment, and the results showed: the difference on rest pain had statistics significance in 2、 16and 24weeks(P<0. 05). The western medical group was superior to TCM group. At other time points, no change of other indexes could be found.(2) Subjective index analysis (evaluation coming from patients, doctors) ① Compared with baseline at the every time point after treatment:both the indexes were improved, the difference of which was of statistics significance (P<0. 01);② The change between two groups between the time points after treatment: the difference had no statistics significance (P>0. 05) .(3) Laboratory index analysis (ESR、 CRP 、 RF 、 IgA 、 IgG 及 IgM)① Compared with baseline: after 12 weeks , ESR、 IgA and IgG had someimprovement in the TCM group, and the difference had statistics significance(P<0.01, P<0. 05); after 24 weeks, ESR、 CRP、 RF 、 IgA 、 IgG and IgM wereall improved, the difference of which were of statistics significance (P<0. 01,P<0. 05); compared with baseline, after 12、 24 weeks, the indexes of the western
medical group were decreased, and the difference had statistics significance (P<0.01, P<0.05) .(2) Compared with two groups after treatment: for RF after 12 weeks and ESR after 24 weeks, the decrease in the western medical group excelled that of the TCM group, the difference had statistics significance (P<0. 01, P<0. 05), other difference had no statistics significance (P>0. 05) . (4) Living quality HAQ analysis① Comparison between mean HAQ of the two groups with baseline: after 12、 24 weeks, HAQ score was improved, and the difference had statistics significance (P<0.01, P<0. 05) .② HAQ mean value between two groups after therapy: the difference had no statistics significance between each week (P>0.05), which meant similar improvement of HAQ in the two groups. 3. Security analysisIn the respect of security, bad events and the abnormality of laboratory index were analyzed. The results were mainly manifested as followings:(1) With the exception of the similarity in the abnormal reaction frequency of alimentary canal symptonu kidney function and abnormal menstruation among the three groups, the frequency of the blood system , liver damage and other abnormal reactions in the TCM group was lower than that of the western medical group.(2) In the respects of the person—time of abnormal liver function that first set in and the degree of abnormality, the TCM group was lower to the other two groups.(3) Considering the patient number of abnormal menstruation that first set in every week, in 2, 4> 12week the TCM group was slightly lower than the western medical group, while the TCM group was a little higher than the western medical group in other weeks.Concluusion:TCM integration plan could effectively inhibit the inflammation, and the effect was similar to that of generally accepted western medicine therapy, the effects of which were manifested as improving joint functions, reducing the pain and swelling, promoting life quality. And what' s more, TCM treatment had some potential value in the respect of delaying the development of RA.In the respects of improving and controlling the inflammation, the
引文
[1] 张乃峥.中国风湿病学的建立与发展.中华内科杂志,1992;31(8):498.
[2] 蒋明.加强类风湿关节炎的临床研究.中华医学杂志,1998;78(3):165～166.
[3] 唐福林.加强对类风湿关节炎早期诊断的实验研究.中华风湿病学杂志,1998;2(1):1～2.
[4] 蒋明,朱立平,林孝义.风湿病学(上册).北京:金盾出版社,1996;第一版,889～913.
[5] 张胜桃,钱宗杰,何培根.类风湿关节炎的治疗进展.医药导报,1999:18(5):303～305.
[6] 于孟学,王迎学,施全胜.类风湿性关节炎发病机理.基础医学与临床,1998:18(4).1～8.
[7] Harris ED. The rationale for combination therapy of rheumatoid arthritis based on pathonphsiology. J Rheumat. 1996; 23(Suppl 44): 2
[8] 叶霜,孙凌云.类风湿关节炎药物治疗进展.中华风湿病学杂志,2000;4(2):111～113.
[9] 焦树德.焦树德临床经验辑要.北京:中国医药科技出版社,1998,第一版,84～109.
[10] 邓翠娥,吴斯金.雷公藤医药作用研究进展.时珍国医国药,2000;11(4):370～371.
[11] 谢洁行,吕薇.雷公藤有效成分与其主要药效关系的探索.吉林中医药,1997;(4):43～44.
[12] 周嘉陵,朱琦,杨晓凌,等.雷公藤制剂副作用的观察.中国中西医结合杂志,1999:19(2):77～79.
[13] 刘强,周莉玲,李锐.雷公藤制剂研究概况.中国药学杂志,1997:32(2):68.
[14] 朱良春.医学微言.北京:人民卫生出版社,1998,第一版经,69～74.
[15] 杨明信.碥石集·痹症研究的回顾和展望.吉林:吉林科学技术出版社,第一版,1999,62～67.
[16] 董明心.益肾蠲痹丸治疗类风湿性关节炎.中国民间疗法,1999,(6):25～26.
[17] 吕爱平,王安民,曾晓莲.益肾蠲痹丸对大鼠实验性痹证影响的病理学研究.中医杂志,1988:(6):49.
[18] 王承德,冯兴华,姜泉,等.痹病系列药Ⅲ期临床总结.中国中医风湿病杂志,2001:4(3):25～49.
[19] 宏宇科技开发有限公司开发.中华医典光盘.湖南:湖南电子音像出版社,2003.
[20] 张海文,赵锡银.调和营卫法治疗类风湿关节炎的体会.中医药学报,1998;26(6):33.
[21] 顾玉蓉,童伯良.重用附子为主治疗重型类风湿关节炎30例.安徽中医学院学报,1996;15(3):25-26.
[22] 祝源隆.活血通络法治疗类风湿关节炎83例.四川中医,1996;14(6):26.
[23] 王风材,王元广,刘绍才.以解毒通络为主治疗类风湿关节炎60例.吉林中医药,1997;17(4):6-7.
[24] 徐桂荣,桑亚雄,徐德茹.益肾温经通痹汤治疗尪痹60例.光明中医,1995;(3):52-54.
[25] 徐玲,田侃明.脾胃学说在治疗类风湿关节炎中的应用.陕西中医,1999;20(4):178-179.
[26] 蒋绍义.益肾活血法治疗类风湿性关节炎的体会.中医杂志,1997:(12):721～722.
[27] 李梢,王永炎.类风湿关节炎从“络”辨治的理论体系初探.中医杂志,2002;43(2):85-88.
[28] 邹伯琦.辨治类风湿性关节炎33例的体会.江西中医药,1995;26(2):26.
[29] 王继学.辨证分型论治类风湿性关节炎48例疗效观察.安徽中医临床杂志,1997;9(2):82-83.
[30] 施旭光,宋述财.辨证治疗类风湿性关节炎57例疗效.现代中西医结合杂志,1999;8(9):1463-1464.
[31] 田文士.类风湿性关节炎的分期辨治体会.河北中医,2002;24(5):350-351.
[32] 宋安尼.重剂黄芪结合分型治疗类风湿性关节炎21例.云南中医中药杂志,1998;19(3):27.
[33] 田河水,李向录.桂枝芍药知母汤加减治疗类风湿性关节炎136例疗效观察.中国中医基础医学杂志,2002;8(8):63.
[42] 李现林.经方治疗类风湿性关节炎114例.国医论坛,1995;10(6):23.
[39] 雷琨美.应用经方乌头汤治疗痹证42例临床体会.云南中医学院学报,1999;22(1):42-43,50.
[40] 史晓,陈建军.风1号合防己黄芪汤治疗类风湿性关节炎46例.南京中医药大学学报,1998;14(1):55.
[41] 程金仓,周海兰,韩梅.黄芪桂枝五物汤加味治疗类风湿性关节炎活动期30例。安 徽中医学院学报,1999;18(2):13-14.
[34] 杨中杰.桂枝芍药知母汤加减治疗急生期类风浊湿性关节炎280例.河南中医药学刊,1999;14(2)46-47.
[35] 邱联群.桂枝芍药知母汤为主治疗类风湿病45例.湖南中医药导报,2000;6(10):22-23.
[36] 王吕成.桂枝芍药知母汤加减治疗类风湿性关节炎34例.四川中医,2000;18(5):22-23.
[37] 房莉萍.桂枝芍药知母汤加减治疗类风湿性关节炎近期疗效观察.江苏中医,2000;21(4):11-12.
[38] 安欣欣.桂枝芍药知母汤治疗类风湿性关节炎48例观察.甘肃中医,2001;14(1):31-32.
[43] 李春英.麻黄加术汤治疗寒湿痹96例疗效观察.黑龙江中医药,2000;(5)12-13.
[44] 吴洋.加味桂枝附子汤治疗寒湿痹证220例临床观察.中国中医药信息杂志,2000;7(2):61.
[45] 周端求.尪痹汤治疗类风湿性关节炎105例临床观察.光明中医,1996;11(4):36-38.
[46] 钱国忠,蔡建成.雷公藤合剂治疗类风湿性关节炎150例疗效观察.浙江中医学院学报,1996;20(6):11-12.
[47] 包丽德.寒湿痹汤治疗风湿寒痹102例.广西中医药,1996;19(6):8-9.
[48] 王慧杰,李保朝.加味风湿净治疗类风湿性关节炎366例.长春中医学院学报,2001;17(1):26.
[49] 郭淑云.康痹胶囊治疗类风湿性关节炎82例临床观察.中国中医药信息杂志,1998:5(4):37-38.
[50] 李家昌,魏雪梅.活血通络止痛饮治疗痹证30例疗效观察.中医药研究,1998;14(1):13-14.
[51] 刘维,王慧,左芳,等.活血清痹方治疗类风湿关节炎60例疗效观察.中国中西医结合杂志,1998:18(12):748.
[52] 陈龙全,张国安,何军.复方竹节参片治疗风湿类疾病218例临床观察.时珍国医国药,1998;9(5):391～392.
[53] 王焕禄,边宝生.清利搜通汤治疗类风湿性关节炎35例临床观察.北京中医,1998;17(5):50-51.
[54] 袁玉红.关于蠲痛丸治疗类风湿性关节炎93例.河北中医,1999;21(10)8-9.
[55] 李瑞琳,刘沛霖.雷公藤缓释片治疗类风湿性关节炎的临床及实验研究.中国中西医结合杂志,1996;16(1):10-13.
[56] 张欣.毛青藤治疗类风湿关节炎1524例临床分析.甘肃中医,1996;9(3):22-23.
[57] 张立亭,张鸣鹏.山苍子根和山苍子治疗类风湿关节炎的临床研究.山东中医杂志,1998;17(12):537-539.
[58] 聂志伟,路通.蚂蚁制剂治疗类风湿关节炎的疗效对比观察.辽宁中医杂志,1995,22(7):304.
[59] 石金桥,张玉亭.温针壮督法治疗类风湿性关节炎疗效观察.针灸临床杂志,1996;12(4):19.
[60] 邓金峰.蜂针治疗类风湿性关节炎53例临床观察.针灸临床杂志,1996;12(7):52～53.
[61] 高雪,高文斌.化痰通络液导入治疗类风湿性关节炎60例疗效观察.中国中医药科技,1998;5(5):316.
[62] 章兴元,王玉明.抗风灵药酒治疗类风湿性关节炎77例临床观察.现代中西医结合杂志,1999;8(7):1084.
[63] 刘东周,冯建华.中药蜡疗治疗痹症的临床研究.山东中医药大学学报,1997;21(6):430-433.
[64] 日洋姑,葛振强.蒸熏治疗类风湿关节炎46例.新疆中医药,2002;20(5):24.
[65] 娄玉钤.娄多峰论治痹病精华.天津:天津科技翻译出版社,1994,第一版,1.
[66] 叶任高主编.内科学.北京:人民卫生出版社,2000,第五版:900.
[67] 中华人民共和国卫生部制定发布.中药新药治疗痹病的临床研究指导原则.北京:中华人民共和国卫生部,1993,第一辑:210-213.
[68] 郑筱萸主编.中药新药治疗类风湿性关节炎的临床研究指导原则.北京:中国医药科技出版社,2002,第一版,5:115-119.
[69] 国家中医药管理局.中医病证诊断疗效标准.南京:南京大学出版社,1994,第一版,7:29-30.
[70] 1988年全国中西医结合风湿类疾病学术会议拟订的诊断标准.实用中医风湿病学,北京:人民卫生出版社,1996,456.
[71] M.L.L. PREVOO. MODIFIED DISEASE ACTIVITY SCORES THAT INCLUDE TWENTY-EIGHT-JOINT COUNTS, ARTHRITIS & RHEUMATISM. 1995; (1): 46.
[72] 李竹.新编实用医学统计方法与技能.北京:中国医药科技出版社,1997,第1版:
[2] 蒋明.加强类风湿关节炎的临床研究.中华医学杂志,1998;78(3):165～166.
[3] 唐福林.加强对类风湿关节炎早期诊断的实验研究.中华风湿病学杂志,1998;2(1):1～2.
[4] 蒋明,朱立平,林孝义.风湿病学(上册).北京:金盾出版社,1996;第一版,889～913.
[5] 张胜桃,钱宗杰,何培根.类风湿关节炎的治疗进展.医药导报,1999:18(5):303～305.
[6] 于孟学,王迎学,施全胜.类风湿性关节炎发病机理.基础医学与临床,1998:18(4).1～8.
[7] Harris ED. The rationale for combination therapy of rheumatoid arthritis based on pathonphsiology. J Rheumat. 1996; 23(Suppl 44): 2
[8] 叶霜,孙凌云.类风湿关节炎药物治疗进展.中华风湿病学杂志,2000;4(2):111～113.
[9] 焦树德.焦树德临床经验辑要.北京:中国医药科技出版社,1998,第一版,84～109.
[10] 邓翠娥,吴斯金.雷公藤医药作用研究进展.时珍国医国药,2000;11(4):370～371.
[11] 谢洁行,吕薇.雷公藤有效成分与其主要药效关系的探索.吉林中医药,1997;(4):43～44.
[12] 周嘉陵,朱琦,杨晓凌,等.雷公藤制剂副作用的观察.中国中西医结合杂志,1999:19(2):77～79.
[13] 刘强,周莉玲,李锐.雷公藤制剂研究概况.中国药学杂志,1997:32(2):68.
[14] 朱良春.医学微言.北京:人民卫生出版社,1998,第一版经,69～74.
[15] 杨明信.碥石集·痹症研究的回顾和展望.吉林:吉林科学技术出版社,第一版,1999,62～67.
[16] 董明心.益肾蠲痹丸治疗类风湿性关节炎.中国民间疗法,1999,(6):25～26.
[17] 吕爱平,王安民,曾晓莲.益肾蠲痹丸对大鼠实验性痹证影响的病理学研究.中医杂志,1988:(6):49.
[18] 王承德,冯兴华,姜泉,等.痹病系列药Ⅲ期临床总结.中国中医风湿病杂志,2001:4(3):25～49.
[19] 宏宇科技开发有限公司开发.中华医典光盘.湖南:湖南电子音像出版社,2003.
[20] 张海文,赵锡银.调和营卫法治疗类风湿关节炎的体会.中医药学报,1998;26(6):33.
[21] 顾玉蓉,童伯良.重用附子为主治疗重型类风湿关节炎30例.安徽中医学院学报,1996;15(3):25-26.
[22] 祝源隆.活血通络法治疗类风湿关节炎83例.四川中医,1996;14(6):26.
[23] 王风材,王元广,刘绍才.以解毒通络为主治疗类风湿关节炎60例.吉林中医药,1997;17(4):6-7.
[24] 徐桂荣,桑亚雄,徐德茹.益肾温经通痹汤治疗尪痹60例.光明中医,1995;(3):52-54.
[25] 徐玲,田侃明.脾胃学说在治疗类风湿关节炎中的应用.陕西中医,1999;20(4):178-179.
[26] 蒋绍义.益肾活血法治疗类风湿性关节炎的体会.中医杂志,1997:(12):721～722.
[27] 李梢,王永炎.类风湿关节炎从“络”辨治的理论体系初探.中医杂志,2002;43(2):85-88.
[28] 邹伯琦.辨治类风湿性关节炎33例的体会.江西中医药,1995;26(2):26.
[29] 王继学.辨证分型论治类风湿性关节炎48例疗效观察.安徽中医临床杂志,1997;9(2):82-83.
[30] 施旭光,宋述财.辨证治疗类风湿性关节炎57例疗效.现代中西医结合杂志,1999;8(9):1463-1464.
[31] 田文士.类风湿性关节炎的分期辨治体会.河北中医,2002;24(5):350-351.
[32] 宋安尼.重剂黄芪结合分型治疗类风湿性关节炎21例.云南中医中药杂志,1998;19(3):27.
[33] 田河水,李向录.桂枝芍药知母汤加减治疗类风湿性关节炎136例疗效观察.中国中医基础医学杂志,2002;8(8):63.
[42] 李现林.经方治疗类风湿性关节炎114例.国医论坛,1995;10(6):23.
[39] 雷琨美.应用经方乌头汤治疗痹证42例临床体会.云南中医学院学报,1999;22(1):42-43,50.
[40] 史晓,陈建军.风1号合防己黄芪汤治疗类风湿性关节炎46例.南京中医药大学学报,1998;14(1):55.
[41] 程金仓,周海兰,韩梅.黄芪桂枝五物汤加味治疗类风湿性关节炎活动期30例。安 徽中医学院学报,1999;18(2):13-14.
[34] 杨中杰.桂枝芍药知母汤加减治疗急生期类风浊湿性关节炎280例.河南中医药学刊,1999;14(2)46-47.
[35] 邱联群.桂枝芍药知母汤为主治疗类风湿病45例.湖南中医药导报,2000;6(10):22-23.
[36] 王吕成.桂枝芍药知母汤加减治疗类风湿性关节炎34例.四川中医,2000;18(5):22-23.
[37] 房莉萍.桂枝芍药知母汤加减治疗类风湿性关节炎近期疗效观察.江苏中医,2000;21(4):11-12.
[38] 安欣欣.桂枝芍药知母汤治疗类风湿性关节炎48例观察.甘肃中医,2001;14(1):31-32.
[43] 李春英.麻黄加术汤治疗寒湿痹96例疗效观察.黑龙江中医药,2000;(5)12-13.
[44] 吴洋.加味桂枝附子汤治疗寒湿痹证220例临床观察.中国中医药信息杂志,2000;7(2):61.
[45] 周端求.尪痹汤治疗类风湿性关节炎105例临床观察.光明中医,1996;11(4):36-38.
[46] 钱国忠,蔡建成.雷公藤合剂治疗类风湿性关节炎150例疗效观察.浙江中医学院学报,1996;20(6):11-12.
[47] 包丽德.寒湿痹汤治疗风湿寒痹102例.广西中医药,1996;19(6):8-9.
[48] 王慧杰,李保朝.加味风湿净治疗类风湿性关节炎366例.长春中医学院学报,2001;17(1):26.
[49] 郭淑云.康痹胶囊治疗类风湿性关节炎82例临床观察.中国中医药信息杂志,1998:5(4):37-38.
[50] 李家昌,魏雪梅.活血通络止痛饮治疗痹证30例疗效观察.中医药研究,1998;14(1):13-14.
[51] 刘维,王慧,左芳,等.活血清痹方治疗类风湿关节炎60例疗效观察.中国中西医结合杂志,1998:18(12):748.
[52] 陈龙全,张国安,何军.复方竹节参片治疗风湿类疾病218例临床观察.时珍国医国药,1998;9(5):391～392.
[53] 王焕禄,边宝生.清利搜通汤治疗类风湿性关节炎35例临床观察.北京中医,1998;17(5):50-51.
[54] 袁玉红.关于蠲痛丸治疗类风湿性关节炎93例.河北中医,1999;21(10)8-9.
[55] 李瑞琳,刘沛霖.雷公藤缓释片治疗类风湿性关节炎的临床及实验研究.中国中西医结合杂志,1996;16(1):10-13.
[56] 张欣.毛青藤治疗类风湿关节炎1524例临床分析.甘肃中医,1996;9(3):22-23.
[57] 张立亭,张鸣鹏.山苍子根和山苍子治疗类风湿关节炎的临床研究.山东中医杂志,1998;17(12):537-539.
[58] 聂志伟,路通.蚂蚁制剂治疗类风湿关节炎的疗效对比观察.辽宁中医杂志,1995,22(7):304.
[59] 石金桥,张玉亭.温针壮督法治疗类风湿性关节炎疗效观察.针灸临床杂志,1996;12(4):19.
[60] 邓金峰.蜂针治疗类风湿性关节炎53例临床观察.针灸临床杂志,1996;12(7):52～53.
[61] 高雪,高文斌.化痰通络液导入治疗类风湿性关节炎60例疗效观察.中国中医药科技,1998;5(5):316.
[62] 章兴元,王玉明.抗风灵药酒治疗类风湿性关节炎77例临床观察.现代中西医结合杂志,1999;8(7):1084.
[63] 刘东周,冯建华.中药蜡疗治疗痹症的临床研究.山东中医药大学学报,1997;21(6):430-433.
[64] 日洋姑,葛振强.蒸熏治疗类风湿关节炎46例.新疆中医药,2002;20(5):24.
[65] 娄玉钤.娄多峰论治痹病精华.天津:天津科技翻译出版社,1994,第一版,1.
[66] 叶任高主编.内科学.北京:人民卫生出版社,2000,第五版:900.
[67] 中华人民共和国卫生部制定发布.中药新药治疗痹病的临床研究指导原则.北京:中华人民共和国卫生部,1993,第一辑:210-213.
[68] 郑筱萸主编.中药新药治疗类风湿性关节炎的临床研究指导原则.北京:中国医药科技出版社,2002,第一版,5:115-119.
[69] 国家中医药管理局.中医病证诊断疗效标准.南京:南京大学出版社,1994,第一版,7:29-30.
[70] 1988年全国中西医结合风湿类疾病学术会议拟订的诊断标准.实用中医风湿病学,北京:人民卫生出版社,1996,456.
[71] M.L.L. PREVOO. MODIFIED DISEASE ACTIVITY SCORES THAT INCLUDE TWENTY-EIGHT-JOINT COUNTS, ARTHRITIS & RHEUMATISM. 1995; (1): 46.
[72] 李竹.新编实用医学统计方法与技能.北京:中国医药科技出版社,1997,第1版:
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