名中医诊疗经验研究：阳虚型失眠症中医诊疗方案的初步构建与优化
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摘要
失眠症是症状严重,病程慢性化,复发率高,躯体、心理、社会功能明显受损,严重影响病人生活质量的一种疾病。中医药对此病治疗有独特的疗效和优势。长期以来,中医学界普遍认为失眠病机总属阳盛阴虚,阳不入阴。治疗常以滋阴清热、宁心安神为主,遣方用药多用寒凉之品,鲜有从阳虚论治者。可是由于人体禀赋的差异、病程的久暂以及施治的失当,阴阳的偏盛偏衰常互相易移,所以临床实际发现有相当部分久治不愈的病人,迭进养阴安神之品无效而转投温补之品常能取得佳效。原因何在?是否是忽略了阳气亏虚的原因?值得深入研究探讨。
名中医在中医理论方面有坚实的基础,对中医理论的本质认识和内涵把握多有独到之处,在临床实践方面有丰富的经验,治疗效果较为突出,可以说,名中医一定程度上代表了中医药的理论和实践精华,他们的诊治经验和理论认识值得关注。目前对于名中医诊治经验的研究,主要限于对名中医经验理论的介绍和大量的医案报道以及临床科研观察等。这些虽然对名中医诊治经验的传承和推广运用起到了一定的作用,但由于其尚未形成结构完整,临床诊疗要素齐备,可供大家临床重复验证与优化的规范化诊疗方案,特别是一些临床思辨过程中的潜在信息和隐性规律的缺如,如适应症的准确全面表述、判定依据与方法、主要矛盾的关系把握等内容,所以很大程度上制约了诊疗经验规范标准化、持续优化、规模化应用等的实现。为此,探索有效的研究方法整理、继承名中医诊疗经验,将无形的经验变成可以供大家操作使用的规范标准的诊疗方案,是值得我们研究的方向。
广东省中医院拥有自己的一批名中医,同时有许多跟师全国名老中医的中青年医生,因此通过对我院名中医失眠症诊疗经验总结分析,确定优化中医药诊疗方案,具有良好的基础和可行性。
研究目的：
本研究鉴于上述研究背景考虑,拟以我院名中医诊疗经验为起点,选择阳虚型失眠症为研究载体,探索性应用定性研究方法(包括内容分析法、文献研究、个体访谈法)构建阳虚型失眠症中医诊疗方案；参考国际上“非随机研究”设计原则,进行可双向分析的前瞻性非随机临床试验,初步对诊疗方案进行验证与优化,旨在为表明该方案潜在的效能和进一步研究的前景提供客观的试验依据,同时为名中医诊疗经验的规范标准化和规模化推广应用提供一定的思路和启示。
研究内容与方法：
本研究为探索性研究,采用定性研究与定量研究相结合的研究方法。具体内容包括：
1.根据本研究目的,结合研究人员现有的失眠(不寐)相关专业理论基础,编制《从阳虚论治失眠相关文献中医专业特征信息采集表》,应用文献计量学、内容分析法等方法,系统收集、评析中医期刊文献中从阳虚论治失眠的专业认识,一定程度上明确阳虚失眠的辨治规律,为下一步阳虚型失眠症中医诊疗方案的构建进行初步的理论准备；
2.在前期文献研究基础上,紧密围绕研究主题,采用定性访谈法对广东省中医院内具有相关专业知识背景(主要是对阳虚型失眠症诊治有深刻理论认识和丰富实践经验)的中医专家进行半结构化访谈,以了解和获取该专家个人诊疗阳虚型失眠症方面的有效经验,初步构建专家个体失眠症中医诊疗方案,为下一步该诊疗方案的进一步验证和优化奠定基础;
3.按照“临床试验研究”诊治评价的要求,在充分重视和细化对象、干预、效应等三个方面的“特征”、“要素”前提下,进行严格的前瞻性病例组观察,试验设计时全面记录对疗效有影响的因素,进行诊疗方案的有效性与安全性初步评价,同时进行有效、无效组病例的对比,比较其初诊时病症因素间的差异,为个体化用药指导、进一步优化诊疗方案的辨识依据等提供客观试验依据。
研究结果：
1.“从阳虚论治失眠”中医期刊文献内容评析
1.1从阳虚论治失眠的中医辨治思路：中医辨病思维的文献占了较大比例(45%,27/60),包括辨病因病机(25%,15/60)、辨病机(13%,8/60)、辨病因(7%,4/60),其次是辨病结合辨证(42%,25/60),主要为辨病机结合脏腑辨证(30%,18/60),而单纯辨证思维所占例较之非常少(7%,4/60)。说明从阳虚论治失眠更多的是强调辨病论治。
1.2从阳虚论治失眠的辨病治疗结果中“阳不入阴,阴阳失交”(48%,13/27)和“阳气亏虚,神失所养”(33%,9/27)占了较高比例；辨病结合辨证治疗的结果中“心肾不交,水火不济”(48%,12/25)和“阳虚阴盛,虚阳浮越,或上扰心神,或心神失养”(24%,6/25)所占比例较高；4篇辨证治疗的文献中,以脏脏辨证和脏腑辨证结合气血津液辨证为主,归类后主要辨证结果有脾胃气亏损、脾阳虚衰、肾阳不足、脾肾两虚、心脾两虚、脾胃虚寒、湿郁不化、心肾不交。
1.3大部分文献明确提及了从阳虚论治失眠的中医辨治依据。关于具体辨治依据角度,从文献篇次频数由高到低依次是阳虚症状及舌脉象,伤阳(气)因素,病程久(久治不愈),既往用药史以及排除因素。
1.4半数以上研究者从阳虚论治失眠所用治法是温阳安神法,其次是温阳补益和温阳劫阴,而温阳祛湿(痰)、温阳解表、温阳理血相对少用。
1.5从阳虚论治失眠使用最多的方是桂枝汤类占35.4%(17/48)；其次为自拟方占22.9%(11/48)、四逆汤类占18.8%(9/48)和肾气丸类,占14.6%(7/48)。超过50％以上文献报道从阳虚论治失眠常用药物依次为附子、甘草、桂枝、龙骨、牡蛎、茯苓、人参、白术。
2.基于定性访谈法的专家个体诊疗方案的构建研究
2.1诊断辨识
辨识分类：阳不入阴,心肾失交：(1)阴阳相对失衡：①生化乏源(肾阳虚)；②阴寒格拒元阳；(2)升降失常：①肝胆失疏；②肺气不降；③中焦枢转不利；(3)窍道经络不通：①痰湿阻遏：②瘀血阻络
2.2干预方案
治则治法：扶阳抑阴,运转枢机,引导气机升降。处方用药：主方：四逆汤加桂枝甘草龙骨牡蛎汤加减；方药：熟附子(先煎)15-30g,干姜15-30g,炙甘草30-60g；桂枝10-15g,龙骨、牡蛎(先煎)各30g。煎服法：先煎熟附子、龙骨、牡蛎30-40分钟,再纳余药同煎1小时。晨间9-10时及午间16-17时温服。
3.阳虚型失眠症中医诊疗方案的初步验证与优化研究
3.1诊疗方案的有效性与安全性初步评价(正向分析)
3.1.1干预前后综合疗效评估
干预后第1月总有效率为37.5%,干预后第2月总有效率为70%,停药后随访第1月总有效率仍为70%。提示干预后第1月已有部分患者开始起效,但总体有效率不高,至干预后第2月总有效率有一个突增,达到起效高峰,停药后随访发现,其总有效率并不没因停药而下降。
3.1.2干预前后匹兹堡睡眠指数(PSQI)和失眠严重程度指数(ISI)评分比较
与干预前比较,干预后患者PSQI总分和七成分评分均有所降低,差异有统计学意义(P<0.05)。其中睡眠障碍因子分在干预前2月期间评分有所下降,但没达到统计学意义(P>0.05),而停药后随访第1月评分下降差异有显著性(P<0.05)。初步分析这可能与中药作用具有累积效应有关。催眠药物因子分下降呈动态波动,在干预后第1月及停药后随访第1月评分下降均未达到统计学意义(P>0.05),而在干预后第2月时评分却有显著性差异(P<0.05)。提示其中有部分患者在中药干预后第2月其催眠药物有所减停,但停止中药干预后又有所反复。与干预前比较,干预后1、2月及停药后随访第1月ISI评分均有下降,差异有显著性意义(P<0.01)。
3.1.3干预前后睡眠客观评估(睡眠监测)比较
与干预前比较,干预后客观睡眠效率和觉醒次数差异有统计学意义(P<0.05)。客观入睡潜伏期和觉醒时间差异接近统计学意义边缘(P=0.07,P=0.06)。而客观睡眠时间和睡眠结构差异均无统计学意义(P>0.05)。初步提示该诊疗方案具有显著改善客观睡眠效率、觉醒次数的作用,部分改善客观入睡潜伏期和觉醒时间的作用(考虑样本量不够),而对客观睡眠时间及睡眠结构无影响。3.1.4干预前后焦虑(SAS)和抑郁自评量表(SDS)及生存质量评分(WHO-BREF)比较
与干预前比较,干预后第1、2月及停药随访第1月患者SAS和SDS评分均明显降低,差异有显著性意义(P<0.01)。与干预前比较,干预后第1、2月及停药随访第1月患者生存质量各领域评分均有改善,差异有显著性意义(P<0.05)。3.1.5镇静催眠药减停及不良反应情况
13例初诊同时服用西药,疗程结束后有3例完全停药,2例由原来1粒/晚减至1粒/周,3例由原来2粒/晚减至1粒/晚,5例西药量维持不变。治疗期间,患者坚持每1～2周复诊,2例患者服药后出现一过性身痒、皮疹、右手大鱼际处脱皮,水泡现象,但均可以耐受,续服药后症状可消失。3.2诊疗方案疗效与病症信息的相关性分析(反向分析)3.2.1有效与无效病例分组情况
本研究以停药后随访第1月疗效进行有效与无效病例分组,其中有效组=痊愈+显效+有效,共28例,其余为无效病例组,共12例。3.2.2有效与无效组间初诊病症信息变量差异比较
通过单因素探索性分析,对有效病例与无效病例初诊时病症信息(包括中医四诊信息、病史特征和各量表评分)间的差异进行比较,采用Pearsonχ2检验或Fisher确切概率,以P<0.05作为入选模型的标准,共纳入变量11个。其中平素怕冷、精神疲乏、烦(急)躁、心悸心慌、畏寒、肢冷、口渴喜热饮、多汗变量与疗效成正相关,而焦虑、便秘、舌尖红变量与疗效呈负相关。提示如果辨识依据中有平素怕冷、精神疲乏、烦(急)躁、心悸心慌、畏寒、肢冷、口渴喜热饮、多汗,且排除焦虑、便秘、舌尖红情况时,运用该方案治疗阳虚型失眠症疗效可能较佳。将单因素探索性分析所纳入的变量进一步行二分类logistic回归分析,以有效和无效二分类为应变量,以上述11个病症信息变量为自变量,筛选自变量的方法为逐步法(纳入标准P<0.05,剔除标准P>0.1)。最后纳入方程的变量为烦(急)躁和畏寒,且有显著性差别(P<0.05),提示该诊疗方案使用的核心辨识依据可能为烦(急)躁和畏寒。
研究结论：
1.本研究通过系统收集、评析从阳虚论治失眠的中医期刊文献,发现中医对阳虚失眠辨治积累了一定的理论认识和实践经验,一定程度上拓展了失眠症的诊治思路,但是从文献数量来看,其总体认识不足。
2.本研究通过探讨,认为对专家个体进行比较深入的半结构访谈,是定性研究在中医临床研究领域的初次应用,初步显示了定性访谈法在构建中医专家个体诊疗方案过程中的适用性,为今后名中医诊疗经验的规范标准化及规模化推广应用提供了一定的思路和参考。
3.初步获得了结构完整,临床诊疗要素齐备,可供临床重复验证与优化的阳虚型失眠症中医诊疗方案。研究表明,以圆运动理论为指导,采用扶阳抑阴,运转枢机,引导气机升降为治法的阳虚型失眠症中医诊疗方案疗效较为可观,具有其临床适用价值,值得进一步探索与证实及临床推广运用。
Backgroud
Insomnia is serious, duration of symptoms, the high recurrence rate physical, psychological, social function significantly impaired and seriously influencing the quality of life of patients of a kind of disease. Traditional Chinese medicine(TCM) treatment of this disease has a unique effect and advantages. For a long time, TCM scholars have generally agreed that the pathogenesis of insomnia is always over-abundant yin with deficient yang, yang does not enter the yin. Treatment on this disease often give priority to nourishing yin and clear heat、tranquilizing the mind, herbal prescription more of the goods with cold, few of according to the ruler from deficient yang. However, Because the differences of human endowments, long or temporary course of disease and misconduct, yin and yang of partial flourishing and failure often easily convert to one another, so there are a substantial part of patients suffering insomnia whose disorders treatment often got good effect by herbal prescription of the goods of warming supplement when poor treatment effect of their disorders by prescription of much the goods of nourish yin and tranquilizing the mind in clinical practice. Why?It is the reason for neglect-ing yang deficiency?It is worthy of deep research and exploration.
TCM experts in TCM theory has a solid foundation, essence of TCM theory to grasp are unique, In clinical practice has a wealth of experience, the treatment effect is more prominent.So to speak, Chinese medicine experts to some extent represents the essence of theory and practice of medicine, diagnosis and treatment of their experience and theoretical understanding are worthy of being concerned.The present study of TCM experts experience of diagnosis and treatment is mainly limited to the description of the TCM experts experiential theory and a lot of medical case reports and clinical resear-ch. these have played certain role in the inheritance and promotion of TCM experts experience of diagnosis and treatment, However, Because of absence of its structural integrity, the clinical diagnosis and treatment elements, repeat for all clinical validation and optimization of standarded diagnosis and treatment programs, In particular, absence of potential information and rules, such as accurate and comprehensive statement of indication, determine the basis and method, grasp the relation between the principal contradicton and so on, it was largely restricted to implement continuous optimization, large-scale applications of specification clinic experience. Therefore, exploring the effective research methods sorting, inherited Chinese Medicine Clinic experience, converting intangible experience to become the standarded opera-tional diagnosis and treatment program, is worthy of our research direction.
Guangdong Provincial Hospital of TCM has its own TCM experts, while a lot of the middle-aged of TCM doctors who learn from national noted old TCM doctors, therefore by summarizing and analyzing the experience of insomnia diognosis and treatment,it has good basis and feasiability to determine the optimization of Traditional Chinese medical diognosis and treatment.
Objectives
The background of the above to be considered, this study plan to take the TCM experts'experience of diagnosis and treatment in our hospital as a starting point,will chose yang deficiency insomnia as the object of study, exploratorily applicate qualitative research methods(including content analysis, literature review, individual interviews) to construct the TCM diagnosis and treatment program of yang deficiency insomnia; Reference to the international "non-randomized study" design principle, to be two-way analysis of prospective non-randomized clinical trial, initial verification and optimization of the diagnosis and treatment is designed to show the potential effectiveness of the program and the prospects for further research to provide an objective test evidence, while to provide some ideas and inspiration for TCM experts'experience of standardization and large-scale application.
Methods
The study is exploratory research, which adopt Qualitative research and quantitative research combination of research methods. The concrete content includes:
1. According to objectives of the study, combined the existing insomnia (BuMei) related theoretical basis of researchers,《Related literature of treatment on insomnia from yang deficiency characteristics of TCM profession information collection form》was formatted, adopting bibliometrics、content analysis and other methods, systematic collecting and analyzing profession congnition with diagnosis and treatment on insomnia from yang deficiency in TCM periodical literature, summarized the law on diagnosis and treatment on yang deficiency insomnia, in order to make theoretical preparation for the initial construction of TCM diagnosis and treatment program of yang deficiency insomnia.
2. Based on previous studies in the literature, closely around the research topic, using qualitative interviews to execute semistructured interviews with expert with relevant profession background (who mainly have a deep theoretical congnition and rich practical experience in diagnosis and treatment on yang deficiency insomnia),to understand and get the expert in personal effective experience of diagnosis and treatment yang deficiency insomnia, initially construct expert individual TCM program of diagnosis and treatment insomnia, for the next step of laying the foundation for further verification and optimization of the diagnosis and treatment.
3. In accordance with the requirements of "clinical trial" treatment evaluation, under the premise of objects、inervention、effects of three aspects of the "features"、"elements" in full attention and refining, taking prospective case strict set of observations, recording comprehensive influen-tial factors on the efficacy when trial was designed, initially evaluate the treatment program's efficacy and safety, meanwhile compare first diagnostic fators dfferences with effective and ineffective cases, in order to guide the individual medication, and provide the evidence for further optimization of diagnosis and treatment programs.
Result
1."The treatment of insomnia from yang deficiency" Content Analysis of Chinese Periodical Literature
1.1 The TCM ideas about diagnosis and treatment on insomnia:literature about TCM differentiation of disease accounted for a larger proportion (45%,27/60), including differentiation of etiology and pathogenesis (25%,15/60), disting-uishing the pathogenesis (13%,8/60), distinguishing the cause (7%,4/60), and the followed is about differentiation of diseases and TCM syndrome (42%,25/60), mainly is how to distinguish the pathogenesis with syndrome differentiation of viscera(30%,18/60), and purely ideas of differentiation of syndrome are in a very small share of cases (7%,4/60). It shows that the treatment of insomnia from the yang deficiency emphasizes more on disease differentiation.
1.2 The results of differentiation diseases of treatment insomnia from yang deficiency shows that " Yang can not insert into yin, yin and yang are failure to connect" (48%,13/27) and "Deficiency of Yang Qi, lost the support of spirit" (33%,9/27) which accounted for a high proportion; while the results of differentiation of diseases and TCM syndrome showed that "disharmony between heart and kidney, disturbance of the regulation between water and fire" (48%,12/25) and "Deficiency of Yang and excess of Yin, upward floating of asthenia-yang, or the disturbance of spirit, or spirit dystrophy" (24%,6/25) is in a high proportion;from these 4 literature about differentiation and treatment, we cold see Syndrome Differentiation of Visceral and Qi, blood, fluid and water are main classification. After classification, Qi deficiency of stomach and spleen, spleen yang deficiency failure, deficiency of kidney yang, deficiency of spleen and kidney, deficiency of heart and spleen, stomach and spleen deficiency, damp accumulated, disharmony between heart and kidney.
1.3 Most of literature refers the evidences of TCM diagnosis and treatment on insomnia from yang deficiency. Based on the specific point of view, we can see the frequency of literature in descending order are symptoms and tongue and pulse of yang deficiency, yang (Qi) wounded factors, course long (long treatment), past medication history and the removal factors.
1.4 More than half of the researchers choose the insomnia treatment prin ciple of warming yang and tranquilizing mind from the yang deficiency. Th e followed is warming yang and invigorating principle and warming yang an d expelling yin principle. However, less application of warming yang and e xpelling damp (phlegm) principle, warming yang and relieving the exterior sydrome principle, warming yang and regulating the blood principle relat ively.
1.5 On the treatment of insomnia from the yang deficiency, the prescription which used most is Gui Zhi Tangs accounted for 35.4%(17/48); and the followed by 22.9% from the intended prescription (11/48), Si Ni Tangs accounted for 18.8%(9/48) and Shen Qi pills which accounting for 14.6%(7/48).Over 50% reported in the literature on the treatment of insomnia from yang deficiency shows that commonly used drugs were Fu Zhi, Gan Cao, Gui Zhi, Long Gu, Mu Li, FU Ling, Ren Sheng, Bai shu.
2.Construction of individual diagnosis and treatment program based on qualitative interviews on expert
2.1 Diagnosis of differentiation
Differentiation Category:yang can not insert into yin, disharmony between heart and kidney:(1)relative imbalance of yin and yang:①biochemical lack of sources (deficiency);②excessive yin hinders yang; (2)movements disorders:①liver and gall bladder loss sparse;②disturbances of pulmonary Qi;③turn negative in the middle heater;(3)Meridian barrier:①phlegm and dampness obstruct;②blood stasis 2.2 intervention programs
Therapeutic Governing principle:support yang and inhibit yin, regulate the pivot and guide the Qi to ascend and descend. Prescription drugs:the main prescription is:Si Ni Tang and Gui Zhi Gan Cao Long Gu Mu Li Tang; Recipe: Shou Fu ZHi(cook first) 15-30g, Gan Jiangl5-30g, Gan Cao30-60g, Long Gu30g, Mu Li30g;decoction method:first cooked Shou Fu Zhi、Long Gu and Mu Li 30-40 minutes, then add other drugs to cook together for 1 hour. Take the warm soup in 9-10 am and 4-5 pm.
3. Study on initial verification and optimization for TCM diagnosis and treatment program of Yang deficiency insomnia
3.1 The efficacy and safety initial evaluation of the diagnosis and treatment program(forward analysis)
3.1.1 Comprehensive efficacy evaluation before and after Intervention
Total effective rate was 37.5% after one month treatment, while total effective rate was 70% after two months treatment. The total effective rate was still 70% after stopping treatment. The research showed some patients felt better after the first month treatment, but total effective rate was not high, which was increasing after two months treatment and reached the highest. Follow-up found that the total effective rate did not decline due to withdrawal.
3.1.2 PSQI and ISI sores before and after intervention
Comparing with the pre-intervention total score of PSQI and scores of seven factors, the scores of post-intervention was lower and there was a significance difference (P<0.05). Sleep disorders scores decreased during the first two months intervention, but did not reach statistical significance (P> 0.05), while the scores decline reach significance difference during after stopping treatment(P<0.05). It maybe relate to the accumulation effect of Chinese herbs. Hypnotic drugs factor scores decreased as dynamic fluctuations, the scores of after one month treatment and one month follow-ups did not reach statistical significance(P> 0.05). However, there was a significant difference after two months treatment (P<0.05). It indicated that some patients decreased the dose of hypnotic drugs after two months intervention, but the dose of hypnotic drugs were given again. Comparing with the pre-intervention, ISI scores of first、second month treatment and after stopping intervention decreased, and it reached the statistical difference (P<0.01) 3.1.3 Comparison of objective assessment of sleep before and after inter-vention (sleep monitoring)
Compared with pre-intervention, the objective sleep efficiency and arousal times are statistically different (P<0.05). Objective differences in sleep latency and waking time were close to the edge of statistical significance (P=0.07, P=0.06).And objective sleep time and sleep structure was no significant difference(P>0.05). It indicated that the therapy greatly improved objective sleep efficiency and reduced the arousal, partially improved objective falling-sleep time and awake time(considering inadequate sample size), but no effect on objective sleeping time and the sleep structure. 3.1.4 Comparisons of SAS, SDS and Life Quality Assessment before and after intervention
Compared with pre-intervention, SAS and SDS scores of post-intervention were obviously decreased and there was a significant difference (P< 0.01). Compared with pre-intervention, results of Life Quality Assessment were improved during the first and second months intervention and after stopping intervention and there was a significant difference (P<0.05) 3.1.5 Reduction and stop of sedative hypnotics and adverse effects
13 patients take western medicine at the initial session,3 of them stopped using western medicine after the TCM treatment,2 of them reduced to the dose to 1 pill per week from 1 pill per night, and 3 of them reduced the dose to 1 pill per night from 2 pill per night,5 of them kept the same dose. During the treatment, patients insist seeing the doctor once one or two week,2 patients had transient body itching, rash, peeling at the right hand thenar, blisters phenomenon, but all the symptoms disappeared when continuing receiving the treatment. 3.2 Correlation analysis of efficacy of diagnosis and treatment programs and diseases information. (Backward analysis) 3.2.1 Effective and ineffective cases of grouping
In this study, groupings were made since the first month follow-ups after the treatment. There were two groups, one is the efficacy group the other is none efficacy group. And the efficacy group included 28 cases of cured patients, markedly efficacy and efficacy. None efficacy group had 12 cases. 3.2.2 Comparisons of the disease information difference of efficacy group and none efficacy group
Through the single factor analysis, this study compared the information difference of initial treatment between the two groups. The information included four TCM diagnostic informations, previous history and all the assessment surveys.11 variables were brought into equation by Pearsonx2 test or Fisher test P<0.05. The results presented that symptoms of cold, mental fatigue, irritability, palpitations, chills, cold extremities, thirst hot drink and sweating were positive related to the efficacy, while the symptoms of anxiety, constipation and red tip tongue were negative related to the efficacy. It indicated that the efficacy would be better treating yang deficency insomnia using the diagnosis and treatment program when symptoms of cold, mental fatigue, irritability dryness, palpitations, chills, cold extremities, thirst hot drink and sweating appeared and no symptoms of anxiety, constipation and red tip tongue. After the logistic regression analysis of containing single factor, efficacy variable and none efficacy variable were set as the dependent variable, above 11 disease information setting as the independent variable. The variable selection method is stepwise (Inclusion criteria P<0.05, exclusion criteria P>0.1). The variable of irritability and chills was included in the final formula, and it indicated a significant difference (P<0.05). It showed the core evidence of differentiation for treatment program was irritability and chills.
Conclusions:
1. In this study, the systematic collection, analysis of the treatment of insomnia from the yang deficiency treatment relating Chinese medicine journal articles, found that Traditional Chinese medicine on the treatment of yang deficiency insomnia and the accumulation of a theoretical knowledge and practical experience. It expanded to some extent the diagnosis and treatments for insomnia. However, the number of the relating articles were not high, Its overall cognition is insufficiency.
2. This study explored the opinion of experts for more in-depth individual semi-structured interviews were the first time of Qualitative Research in clinical TCM fields. It indicated the advantages of using qualitative research of TCM specialty and provides some ideas and references for future standardization and large-scale application of TCM experts'clinical experience.
3. This study initially obtained complete structre, the clinical diagnosis and treatment elements, suitable for clinical repetitive validation and optimi-zation of TCM diagnois and treatment program of yang deficiency insomnia. The results showed that the circular movement theory, suppression ying while strengthening yang, cardinal running and guide air-lift method for the treatment of Chinese medicine clinics in the treatment of yang deficency insomnia are more significant effect. It had the clinical application value, worthy of further exploration and confirmation, and clinically promoting the use.
名中医在中医理论方面有坚实的基础,对中医理论的本质认识和内涵把握多有独到之处,在临床实践方面有丰富的经验,治疗效果较为突出,可以说,名中医一定程度上代表了中医药的理论和实践精华,他们的诊治经验和理论认识值得关注。目前对于名中医诊治经验的研究,主要限于对名中医经验理论的介绍和大量的医案报道以及临床科研观察等。这些虽然对名中医诊治经验的传承和推广运用起到了一定的作用,但由于其尚未形成结构完整,临床诊疗要素齐备,可供大家临床重复验证与优化的规范化诊疗方案,特别是一些临床思辨过程中的潜在信息和隐性规律的缺如,如适应症的准确全面表述、判定依据与方法、主要矛盾的关系把握等内容,所以很大程度上制约了诊疗经验规范标准化、持续优化、规模化应用等的实现。为此,探索有效的研究方法整理、继承名中医诊疗经验,将无形的经验变成可以供大家操作使用的规范标准的诊疗方案,是值得我们研究的方向。
广东省中医院拥有自己的一批名中医,同时有许多跟师全国名老中医的中青年医生,因此通过对我院名中医失眠症诊疗经验总结分析,确定优化中医药诊疗方案,具有良好的基础和可行性。
研究目的：
本研究鉴于上述研究背景考虑,拟以我院名中医诊疗经验为起点,选择阳虚型失眠症为研究载体,探索性应用定性研究方法(包括内容分析法、文献研究、个体访谈法)构建阳虚型失眠症中医诊疗方案；参考国际上“非随机研究”设计原则,进行可双向分析的前瞻性非随机临床试验,初步对诊疗方案进行验证与优化,旨在为表明该方案潜在的效能和进一步研究的前景提供客观的试验依据,同时为名中医诊疗经验的规范标准化和规模化推广应用提供一定的思路和启示。
研究内容与方法：
本研究为探索性研究,采用定性研究与定量研究相结合的研究方法。具体内容包括：
1.根据本研究目的,结合研究人员现有的失眠(不寐)相关专业理论基础,编制《从阳虚论治失眠相关文献中医专业特征信息采集表》,应用文献计量学、内容分析法等方法,系统收集、评析中医期刊文献中从阳虚论治失眠的专业认识,一定程度上明确阳虚失眠的辨治规律,为下一步阳虚型失眠症中医诊疗方案的构建进行初步的理论准备；
2.在前期文献研究基础上,紧密围绕研究主题,采用定性访谈法对广东省中医院内具有相关专业知识背景(主要是对阳虚型失眠症诊治有深刻理论认识和丰富实践经验)的中医专家进行半结构化访谈,以了解和获取该专家个人诊疗阳虚型失眠症方面的有效经验,初步构建专家个体失眠症中医诊疗方案,为下一步该诊疗方案的进一步验证和优化奠定基础;
3.按照“临床试验研究”诊治评价的要求,在充分重视和细化对象、干预、效应等三个方面的“特征”、“要素”前提下,进行严格的前瞻性病例组观察,试验设计时全面记录对疗效有影响的因素,进行诊疗方案的有效性与安全性初步评价,同时进行有效、无效组病例的对比,比较其初诊时病症因素间的差异,为个体化用药指导、进一步优化诊疗方案的辨识依据等提供客观试验依据。
研究结果：
1.“从阳虚论治失眠”中医期刊文献内容评析
1.1从阳虚论治失眠的中医辨治思路：中医辨病思维的文献占了较大比例(45%,27/60),包括辨病因病机(25%,15/60)、辨病机(13%,8/60)、辨病因(7%,4/60),其次是辨病结合辨证(42%,25/60),主要为辨病机结合脏腑辨证(30%,18/60),而单纯辨证思维所占例较之非常少(7%,4/60)。说明从阳虚论治失眠更多的是强调辨病论治。
1.2从阳虚论治失眠的辨病治疗结果中“阳不入阴,阴阳失交”(48%,13/27)和“阳气亏虚,神失所养”(33%,9/27)占了较高比例；辨病结合辨证治疗的结果中“心肾不交,水火不济”(48%,12/25)和“阳虚阴盛,虚阳浮越,或上扰心神,或心神失养”(24%,6/25)所占比例较高；4篇辨证治疗的文献中,以脏脏辨证和脏腑辨证结合气血津液辨证为主,归类后主要辨证结果有脾胃气亏损、脾阳虚衰、肾阳不足、脾肾两虚、心脾两虚、脾胃虚寒、湿郁不化、心肾不交。
1.3大部分文献明确提及了从阳虚论治失眠的中医辨治依据。关于具体辨治依据角度,从文献篇次频数由高到低依次是阳虚症状及舌脉象,伤阳(气)因素,病程久(久治不愈),既往用药史以及排除因素。
1.4半数以上研究者从阳虚论治失眠所用治法是温阳安神法,其次是温阳补益和温阳劫阴,而温阳祛湿(痰)、温阳解表、温阳理血相对少用。
1.5从阳虚论治失眠使用最多的方是桂枝汤类占35.4%(17/48)；其次为自拟方占22.9%(11/48)、四逆汤类占18.8%(9/48)和肾气丸类,占14.6%(7/48)。超过50％以上文献报道从阳虚论治失眠常用药物依次为附子、甘草、桂枝、龙骨、牡蛎、茯苓、人参、白术。
2.基于定性访谈法的专家个体诊疗方案的构建研究
2.1诊断辨识
辨识分类：阳不入阴,心肾失交：(1)阴阳相对失衡：①生化乏源(肾阳虚)；②阴寒格拒元阳；(2)升降失常：①肝胆失疏；②肺气不降；③中焦枢转不利；(3)窍道经络不通：①痰湿阻遏：②瘀血阻络
2.2干预方案
治则治法：扶阳抑阴,运转枢机,引导气机升降。处方用药：主方：四逆汤加桂枝甘草龙骨牡蛎汤加减；方药：熟附子(先煎)15-30g,干姜15-30g,炙甘草30-60g；桂枝10-15g,龙骨、牡蛎(先煎)各30g。煎服法：先煎熟附子、龙骨、牡蛎30-40分钟,再纳余药同煎1小时。晨间9-10时及午间16-17时温服。
3.阳虚型失眠症中医诊疗方案的初步验证与优化研究
3.1诊疗方案的有效性与安全性初步评价(正向分析)
3.1.1干预前后综合疗效评估
干预后第1月总有效率为37.5%,干预后第2月总有效率为70%,停药后随访第1月总有效率仍为70%。提示干预后第1月已有部分患者开始起效,但总体有效率不高,至干预后第2月总有效率有一个突增,达到起效高峰,停药后随访发现,其总有效率并不没因停药而下降。
3.1.2干预前后匹兹堡睡眠指数(PSQI)和失眠严重程度指数(ISI)评分比较
与干预前比较,干预后患者PSQI总分和七成分评分均有所降低,差异有统计学意义(P<0.05)。其中睡眠障碍因子分在干预前2月期间评分有所下降,但没达到统计学意义(P>0.05),而停药后随访第1月评分下降差异有显著性(P<0.05)。初步分析这可能与中药作用具有累积效应有关。催眠药物因子分下降呈动态波动,在干预后第1月及停药后随访第1月评分下降均未达到统计学意义(P>0.05),而在干预后第2月时评分却有显著性差异(P<0.05)。提示其中有部分患者在中药干预后第2月其催眠药物有所减停,但停止中药干预后又有所反复。与干预前比较,干预后1、2月及停药后随访第1月ISI评分均有下降,差异有显著性意义(P<0.01)。
3.1.3干预前后睡眠客观评估(睡眠监测)比较
与干预前比较,干预后客观睡眠效率和觉醒次数差异有统计学意义(P<0.05)。客观入睡潜伏期和觉醒时间差异接近统计学意义边缘(P=0.07,P=0.06)。而客观睡眠时间和睡眠结构差异均无统计学意义(P>0.05)。初步提示该诊疗方案具有显著改善客观睡眠效率、觉醒次数的作用,部分改善客观入睡潜伏期和觉醒时间的作用(考虑样本量不够),而对客观睡眠时间及睡眠结构无影响。3.1.4干预前后焦虑(SAS)和抑郁自评量表(SDS)及生存质量评分(WHO-BREF)比较
与干预前比较,干预后第1、2月及停药随访第1月患者SAS和SDS评分均明显降低,差异有显著性意义(P<0.01)。与干预前比较,干预后第1、2月及停药随访第1月患者生存质量各领域评分均有改善,差异有显著性意义(P<0.05)。3.1.5镇静催眠药减停及不良反应情况
13例初诊同时服用西药,疗程结束后有3例完全停药,2例由原来1粒/晚减至1粒/周,3例由原来2粒/晚减至1粒/晚,5例西药量维持不变。治疗期间,患者坚持每1～2周复诊,2例患者服药后出现一过性身痒、皮疹、右手大鱼际处脱皮,水泡现象,但均可以耐受,续服药后症状可消失。3.2诊疗方案疗效与病症信息的相关性分析(反向分析)3.2.1有效与无效病例分组情况
本研究以停药后随访第1月疗效进行有效与无效病例分组,其中有效组=痊愈+显效+有效,共28例,其余为无效病例组,共12例。3.2.2有效与无效组间初诊病症信息变量差异比较
通过单因素探索性分析,对有效病例与无效病例初诊时病症信息(包括中医四诊信息、病史特征和各量表评分)间的差异进行比较,采用Pearsonχ2检验或Fisher确切概率,以P<0.05作为入选模型的标准,共纳入变量11个。其中平素怕冷、精神疲乏、烦(急)躁、心悸心慌、畏寒、肢冷、口渴喜热饮、多汗变量与疗效成正相关,而焦虑、便秘、舌尖红变量与疗效呈负相关。提示如果辨识依据中有平素怕冷、精神疲乏、烦(急)躁、心悸心慌、畏寒、肢冷、口渴喜热饮、多汗,且排除焦虑、便秘、舌尖红情况时,运用该方案治疗阳虚型失眠症疗效可能较佳。将单因素探索性分析所纳入的变量进一步行二分类logistic回归分析,以有效和无效二分类为应变量,以上述11个病症信息变量为自变量,筛选自变量的方法为逐步法(纳入标准P<0.05,剔除标准P>0.1)。最后纳入方程的变量为烦(急)躁和畏寒,且有显著性差别(P<0.05),提示该诊疗方案使用的核心辨识依据可能为烦(急)躁和畏寒。
研究结论：
1.本研究通过系统收集、评析从阳虚论治失眠的中医期刊文献,发现中医对阳虚失眠辨治积累了一定的理论认识和实践经验,一定程度上拓展了失眠症的诊治思路,但是从文献数量来看,其总体认识不足。
2.本研究通过探讨,认为对专家个体进行比较深入的半结构访谈,是定性研究在中医临床研究领域的初次应用,初步显示了定性访谈法在构建中医专家个体诊疗方案过程中的适用性,为今后名中医诊疗经验的规范标准化及规模化推广应用提供了一定的思路和参考。
3.初步获得了结构完整,临床诊疗要素齐备,可供临床重复验证与优化的阳虚型失眠症中医诊疗方案。研究表明,以圆运动理论为指导,采用扶阳抑阴,运转枢机,引导气机升降为治法的阳虚型失眠症中医诊疗方案疗效较为可观,具有其临床适用价值,值得进一步探索与证实及临床推广运用。
Backgroud
Insomnia is serious, duration of symptoms, the high recurrence rate physical, psychological, social function significantly impaired and seriously influencing the quality of life of patients of a kind of disease. Traditional Chinese medicine(TCM) treatment of this disease has a unique effect and advantages. For a long time, TCM scholars have generally agreed that the pathogenesis of insomnia is always over-abundant yin with deficient yang, yang does not enter the yin. Treatment on this disease often give priority to nourishing yin and clear heat、tranquilizing the mind, herbal prescription more of the goods with cold, few of according to the ruler from deficient yang. However, Because the differences of human endowments, long or temporary course of disease and misconduct, yin and yang of partial flourishing and failure often easily convert to one another, so there are a substantial part of patients suffering insomnia whose disorders treatment often got good effect by herbal prescription of the goods of warming supplement when poor treatment effect of their disorders by prescription of much the goods of nourish yin and tranquilizing the mind in clinical practice. Why?It is the reason for neglect-ing yang deficiency?It is worthy of deep research and exploration.
TCM experts in TCM theory has a solid foundation, essence of TCM theory to grasp are unique, In clinical practice has a wealth of experience, the treatment effect is more prominent.So to speak, Chinese medicine experts to some extent represents the essence of theory and practice of medicine, diagnosis and treatment of their experience and theoretical understanding are worthy of being concerned.The present study of TCM experts experience of diagnosis and treatment is mainly limited to the description of the TCM experts experiential theory and a lot of medical case reports and clinical resear-ch. these have played certain role in the inheritance and promotion of TCM experts experience of diagnosis and treatment, However, Because of absence of its structural integrity, the clinical diagnosis and treatment elements, repeat for all clinical validation and optimization of standarded diagnosis and treatment programs, In particular, absence of potential information and rules, such as accurate and comprehensive statement of indication, determine the basis and method, grasp the relation between the principal contradicton and so on, it was largely restricted to implement continuous optimization, large-scale applications of specification clinic experience. Therefore, exploring the effective research methods sorting, inherited Chinese Medicine Clinic experience, converting intangible experience to become the standarded opera-tional diagnosis and treatment program, is worthy of our research direction.
Guangdong Provincial Hospital of TCM has its own TCM experts, while a lot of the middle-aged of TCM doctors who learn from national noted old TCM doctors, therefore by summarizing and analyzing the experience of insomnia diognosis and treatment,it has good basis and feasiability to determine the optimization of Traditional Chinese medical diognosis and treatment.
Objectives
The background of the above to be considered, this study plan to take the TCM experts'experience of diagnosis and treatment in our hospital as a starting point,will chose yang deficiency insomnia as the object of study, exploratorily applicate qualitative research methods(including content analysis, literature review, individual interviews) to construct the TCM diagnosis and treatment program of yang deficiency insomnia; Reference to the international "non-randomized study" design principle, to be two-way analysis of prospective non-randomized clinical trial, initial verification and optimization of the diagnosis and treatment is designed to show the potential effectiveness of the program and the prospects for further research to provide an objective test evidence, while to provide some ideas and inspiration for TCM experts'experience of standardization and large-scale application.
Methods
The study is exploratory research, which adopt Qualitative research and quantitative research combination of research methods. The concrete content includes:
1. According to objectives of the study, combined the existing insomnia (BuMei) related theoretical basis of researchers,《Related literature of treatment on insomnia from yang deficiency characteristics of TCM profession information collection form》was formatted, adopting bibliometrics、content analysis and other methods, systematic collecting and analyzing profession congnition with diagnosis and treatment on insomnia from yang deficiency in TCM periodical literature, summarized the law on diagnosis and treatment on yang deficiency insomnia, in order to make theoretical preparation for the initial construction of TCM diagnosis and treatment program of yang deficiency insomnia.
2. Based on previous studies in the literature, closely around the research topic, using qualitative interviews to execute semistructured interviews with expert with relevant profession background (who mainly have a deep theoretical congnition and rich practical experience in diagnosis and treatment on yang deficiency insomnia),to understand and get the expert in personal effective experience of diagnosis and treatment yang deficiency insomnia, initially construct expert individual TCM program of diagnosis and treatment insomnia, for the next step of laying the foundation for further verification and optimization of the diagnosis and treatment.
3. In accordance with the requirements of "clinical trial" treatment evaluation, under the premise of objects、inervention、effects of three aspects of the "features"、"elements" in full attention and refining, taking prospective case strict set of observations, recording comprehensive influen-tial factors on the efficacy when trial was designed, initially evaluate the treatment program's efficacy and safety, meanwhile compare first diagnostic fators dfferences with effective and ineffective cases, in order to guide the individual medication, and provide the evidence for further optimization of diagnosis and treatment programs.
Result
1."The treatment of insomnia from yang deficiency" Content Analysis of Chinese Periodical Literature
1.1 The TCM ideas about diagnosis and treatment on insomnia:literature about TCM differentiation of disease accounted for a larger proportion (45%,27/60), including differentiation of etiology and pathogenesis (25%,15/60), disting-uishing the pathogenesis (13%,8/60), distinguishing the cause (7%,4/60), and the followed is about differentiation of diseases and TCM syndrome (42%,25/60), mainly is how to distinguish the pathogenesis with syndrome differentiation of viscera(30%,18/60), and purely ideas of differentiation of syndrome are in a very small share of cases (7%,4/60). It shows that the treatment of insomnia from the yang deficiency emphasizes more on disease differentiation.
1.2 The results of differentiation diseases of treatment insomnia from yang deficiency shows that " Yang can not insert into yin, yin and yang are failure to connect" (48%,13/27) and "Deficiency of Yang Qi, lost the support of spirit" (33%,9/27) which accounted for a high proportion; while the results of differentiation of diseases and TCM syndrome showed that "disharmony between heart and kidney, disturbance of the regulation between water and fire" (48%,12/25) and "Deficiency of Yang and excess of Yin, upward floating of asthenia-yang, or the disturbance of spirit, or spirit dystrophy" (24%,6/25) is in a high proportion;from these 4 literature about differentiation and treatment, we cold see Syndrome Differentiation of Visceral and Qi, blood, fluid and water are main classification. After classification, Qi deficiency of stomach and spleen, spleen yang deficiency failure, deficiency of kidney yang, deficiency of spleen and kidney, deficiency of heart and spleen, stomach and spleen deficiency, damp accumulated, disharmony between heart and kidney.
1.3 Most of literature refers the evidences of TCM diagnosis and treatment on insomnia from yang deficiency. Based on the specific point of view, we can see the frequency of literature in descending order are symptoms and tongue and pulse of yang deficiency, yang (Qi) wounded factors, course long (long treatment), past medication history and the removal factors.
1.4 More than half of the researchers choose the insomnia treatment prin ciple of warming yang and tranquilizing mind from the yang deficiency. Th e followed is warming yang and invigorating principle and warming yang an d expelling yin principle. However, less application of warming yang and e xpelling damp (phlegm) principle, warming yang and relieving the exterior sydrome principle, warming yang and regulating the blood principle relat ively.
1.5 On the treatment of insomnia from the yang deficiency, the prescription which used most is Gui Zhi Tangs accounted for 35.4%(17/48); and the followed by 22.9% from the intended prescription (11/48), Si Ni Tangs accounted for 18.8%(9/48) and Shen Qi pills which accounting for 14.6%(7/48).Over 50% reported in the literature on the treatment of insomnia from yang deficiency shows that commonly used drugs were Fu Zhi, Gan Cao, Gui Zhi, Long Gu, Mu Li, FU Ling, Ren Sheng, Bai shu.
2.Construction of individual diagnosis and treatment program based on qualitative interviews on expert
2.1 Diagnosis of differentiation
Differentiation Category:yang can not insert into yin, disharmony between heart and kidney:(1)relative imbalance of yin and yang:①biochemical lack of sources (deficiency);②excessive yin hinders yang; (2)movements disorders:①liver and gall bladder loss sparse;②disturbances of pulmonary Qi;③turn negative in the middle heater;(3)Meridian barrier:①phlegm and dampness obstruct;②blood stasis 2.2 intervention programs
Therapeutic Governing principle:support yang and inhibit yin, regulate the pivot and guide the Qi to ascend and descend. Prescription drugs:the main prescription is:Si Ni Tang and Gui Zhi Gan Cao Long Gu Mu Li Tang; Recipe: Shou Fu ZHi(cook first) 15-30g, Gan Jiangl5-30g, Gan Cao30-60g, Long Gu30g, Mu Li30g;decoction method:first cooked Shou Fu Zhi、Long Gu and Mu Li 30-40 minutes, then add other drugs to cook together for 1 hour. Take the warm soup in 9-10 am and 4-5 pm.
3. Study on initial verification and optimization for TCM diagnosis and treatment program of Yang deficiency insomnia
3.1 The efficacy and safety initial evaluation of the diagnosis and treatment program(forward analysis)
3.1.1 Comprehensive efficacy evaluation before and after Intervention
Total effective rate was 37.5% after one month treatment, while total effective rate was 70% after two months treatment. The total effective rate was still 70% after stopping treatment. The research showed some patients felt better after the first month treatment, but total effective rate was not high, which was increasing after two months treatment and reached the highest. Follow-up found that the total effective rate did not decline due to withdrawal.
3.1.2 PSQI and ISI sores before and after intervention
Comparing with the pre-intervention total score of PSQI and scores of seven factors, the scores of post-intervention was lower and there was a significance difference (P<0.05). Sleep disorders scores decreased during the first two months intervention, but did not reach statistical significance (P> 0.05), while the scores decline reach significance difference during after stopping treatment(P<0.05). It maybe relate to the accumulation effect of Chinese herbs. Hypnotic drugs factor scores decreased as dynamic fluctuations, the scores of after one month treatment and one month follow-ups did not reach statistical significance(P> 0.05). However, there was a significant difference after two months treatment (P<0.05). It indicated that some patients decreased the dose of hypnotic drugs after two months intervention, but the dose of hypnotic drugs were given again. Comparing with the pre-intervention, ISI scores of first、second month treatment and after stopping intervention decreased, and it reached the statistical difference (P<0.01) 3.1.3 Comparison of objective assessment of sleep before and after inter-vention (sleep monitoring)
Compared with pre-intervention, the objective sleep efficiency and arousal times are statistically different (P<0.05). Objective differences in sleep latency and waking time were close to the edge of statistical significance (P=0.07, P=0.06).And objective sleep time and sleep structure was no significant difference(P>0.05). It indicated that the therapy greatly improved objective sleep efficiency and reduced the arousal, partially improved objective falling-sleep time and awake time(considering inadequate sample size), but no effect on objective sleeping time and the sleep structure. 3.1.4 Comparisons of SAS, SDS and Life Quality Assessment before and after intervention
Compared with pre-intervention, SAS and SDS scores of post-intervention were obviously decreased and there was a significant difference (P< 0.01). Compared with pre-intervention, results of Life Quality Assessment were improved during the first and second months intervention and after stopping intervention and there was a significant difference (P<0.05) 3.1.5 Reduction and stop of sedative hypnotics and adverse effects
13 patients take western medicine at the initial session,3 of them stopped using western medicine after the TCM treatment,2 of them reduced to the dose to 1 pill per week from 1 pill per night, and 3 of them reduced the dose to 1 pill per night from 2 pill per night,5 of them kept the same dose. During the treatment, patients insist seeing the doctor once one or two week,2 patients had transient body itching, rash, peeling at the right hand thenar, blisters phenomenon, but all the symptoms disappeared when continuing receiving the treatment. 3.2 Correlation analysis of efficacy of diagnosis and treatment programs and diseases information. (Backward analysis) 3.2.1 Effective and ineffective cases of grouping
In this study, groupings were made since the first month follow-ups after the treatment. There were two groups, one is the efficacy group the other is none efficacy group. And the efficacy group included 28 cases of cured patients, markedly efficacy and efficacy. None efficacy group had 12 cases. 3.2.2 Comparisons of the disease information difference of efficacy group and none efficacy group
Through the single factor analysis, this study compared the information difference of initial treatment between the two groups. The information included four TCM diagnostic informations, previous history and all the assessment surveys.11 variables were brought into equation by Pearsonx2 test or Fisher test P<0.05. The results presented that symptoms of cold, mental fatigue, irritability, palpitations, chills, cold extremities, thirst hot drink and sweating were positive related to the efficacy, while the symptoms of anxiety, constipation and red tip tongue were negative related to the efficacy. It indicated that the efficacy would be better treating yang deficency insomnia using the diagnosis and treatment program when symptoms of cold, mental fatigue, irritability dryness, palpitations, chills, cold extremities, thirst hot drink and sweating appeared and no symptoms of anxiety, constipation and red tip tongue. After the logistic regression analysis of containing single factor, efficacy variable and none efficacy variable were set as the dependent variable, above 11 disease information setting as the independent variable. The variable selection method is stepwise (Inclusion criteria P<0.05, exclusion criteria P>0.1). The variable of irritability and chills was included in the final formula, and it indicated a significant difference (P<0.05). It showed the core evidence of differentiation for treatment program was irritability and chills.
Conclusions:
1. In this study, the systematic collection, analysis of the treatment of insomnia from the yang deficiency treatment relating Chinese medicine journal articles, found that Traditional Chinese medicine on the treatment of yang deficiency insomnia and the accumulation of a theoretical knowledge and practical experience. It expanded to some extent the diagnosis and treatments for insomnia. However, the number of the relating articles were not high, Its overall cognition is insufficiency.
2. This study explored the opinion of experts for more in-depth individual semi-structured interviews were the first time of Qualitative Research in clinical TCM fields. It indicated the advantages of using qualitative research of TCM specialty and provides some ideas and references for future standardization and large-scale application of TCM experts'clinical experience.
3. This study initially obtained complete structre, the clinical diagnosis and treatment elements, suitable for clinical repetitive validation and optimi-zation of TCM diagnois and treatment program of yang deficiency insomnia. The results showed that the circular movement theory, suppression ying while strengthening yang, cardinal running and guide air-lift method for the treatment of Chinese medicine clinics in the treatment of yang deficency insomnia are more significant effect. It had the clinical application value, worthy of further exploration and confirmation, and clinically promoting the use.
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