北京地区男男性接触者（MSM）艾滋病症证分布规律的研究
|
摘要
艾滋病全称为获得性免疫缺陷综合征(acquired immunodeficiency syndrome, AIDS),该病由感染人免疫缺陷病毒(human immunodeficiency virus, HIV)而引起,导致被感染者免疫功能的部分或完全丧失,继而发生多系统、多器官、多病原体的复合感染(机会性感染)和肿瘤等,临床表现形式多种多样。该病传播速度快、死亡率高,目前仍无法治愈,但由于抗病毒疗法(HAART)的出现,使本病成为一种慢性可控性疾病。
在中医学整体观念和辨证论治的指导下,从90年代开始,进行了中医药治疗艾滋病的临床实践,取得了一定的临床疗效。但是,对于艾滋病中医证候方面的研究起步较晚,不同感染途径、不同地域、不同病期艾滋病患者的中医证候类型和演变规律尚不清楚,证候分类只见于临床医生的一般性临床总结文章中,缺乏大规模、系统的、前瞻性的艾滋病中医证候研究结果。因此,有必要对艾滋病的证候分类和证候演变规律进行研究,为更好地进行艾滋病的中医辨证论证,提高临床疗效奠定基础。
目的
探讨北京地区男男性接触者(MSM)艾滋病症状、证型分布规律以及与临床分期、免疫功能的相关性。
方法
本研究是国家科技重大专项“艾滋病中医证候学研究”(课题号：2008ZX10005-001)的一部分,主要由三部分组成：第一部分文献研究,主要围绕艾滋病的症状、证候进行文献检索、分析、提炼；第二部分主要阐述艾滋病中医四诊信息采集表的研制过程,包括艾滋病四诊信息采集表的内容、结构、条目池的确立；研制艾滋病四诊信息采集表的技术路线以及调查表的维度、信度、效度分析等。第三部分主要阐述北京地区男男性接触者(MSM)艾滋病症证分布规律以及与临床分期、免疫功能的相关性研究,同时探讨PRO量表在症证研究中的应用。现简要阐述如下：
结果
第一部分文献研究
共检索出有关艾滋病的中医研究方面的文献近500余篇。其中涉及中医证候研究的共44篇,所有的文献中有证型记载的文献很少,而且每篇文献的辨证方法不同,有按照五脏分型,有按三焦辨证,结果出现了不同表述的证型143种之多,同时出现两次的表述的只有21种,其中无症状期证型主要涉及14个,湿热内蕴、气郁痰凝、气阴两虚、肝郁气滞等,AIDS期主要涉及12个,湿热内蕴、痰热蕴肺、气郁痰凝、痰瘀互结等。症状条目相对比较集中,所有文献关注的症状基本相同,出现频率比较高的有乏力、发热、皮疹、咳嗽、腹泻等。
第二部分艾滋病四诊信息采集表的研制
本部分主要阐述艾滋病四诊信息采集表的研制过程,包括拟研制的内容及研究的技术路线；艾滋病四诊信息采集表的构架及条目池的构建；条目筛选、规范以及信、效度分析。
1艾滋病四诊信息采集表的构建
根据文献研究结果,以《中药新药指导原则》、《中医诊断学》以及《中华人民共和国国家标准GB/T 16751.2-1997》为依据构建条目,初步形成调查表的框架。
2专家咨询
第一轮专家咨询采用函审与访谈的形式相结合请中国中医科学院从事艾滋病工作10年以上的专家对调查表提出针对调查表的结构,条目设置,提出意见和建议。发出23份问卷,回收22份,少数进行了访谈。专家意见汇总简要如下(详见附件)：根据专家意见条目按照脏腑进行设置,细化条目6条,增加条目5条。
第二轮采用专家问卷形式,备选条目来源于上一轮专家咨询经统计、讨论、整理、规范后保留的症状。根据专家经验判断症状在艾滋病病程中临床出现频率的高低,以及对病程发展的重要性角度考虑,作为筛选条目的依据之一。根据各个症状出现频率以及特异性进行排序,综合考虑删除症状如下：瘀斑、骨蒸。
3条目的规范
对已筛选出的条目进行规范,力求用语的标准化。症状的规范化包括症状术语及其内涵的规范、症状严重程度量化分级的规范、症状辨证学意义的规范三方面的内容。根据《中华人民共和国·中医临床诊疗术语》进行症状术语及其内涵的规范共有8条进行了拆分,10条进行了规范表述,删除了4条。在症状的量化分级方面依据症状的性质特征、出现频率、出现情境、持续时间、伴随的其它症状、对药物的依赖程度、与外界刺激的关系及对日常生活影响程度等项目中的一项或多项划分轻、中、重。症状辨证学意义的规范如：腹痛的性质,大便的性状等。
4信度、效度
内部信度、分半信度以及结构效度均可。
第三部分北京地区男男性接触者(MSM)艾滋病症证分布规律的研究
1症状分布规律
总体印象：以乏力、健忘、烦躁、性欲减退、情绪抑郁、腰膝酸痛等症状为主,与文献研究比较存在一定的差异,发热、咳嗽、腹泻等症状检出率不高,考虑可能与生活条件和感染途径有关,同时提示男男性接触者(MSM)艾滋病主要涉及肝、脾、肾等脏腑,肺系症状相对较少；50%以上的患者有烦躁、情绪抑郁等情志异常表现。
四种途径获得的症状信息的对比研究(文献研究、专家咨询、临床调查、PRO量表)：文献研究与专家咨询的结果比较一致,与临床调查、PRO量表有一定的差别,排名前十位的症状中,本次调查中没有文献以及专家咨询中出现的腹泻、发热、咳嗽等,出现了情志方面的症状。分析原因可能由于文献研究、专家对有偿采供血感染的患者关注比较多,没有针对男男性接触人群的研究。
2证型分布规律
总体印象：以气虚为内因(检出率41.3%),累及阴阳,兼有精亏,火(热)、湿邪为外因,兼有气滞、痰、饮、瘀血。病位在脾,以肝脾为主,累及肺肾,多以里证为主。舌象：以暗红舌、黄厚腻苔多见,伴有齿痕、瘀斑,与文献报告的艾滋病人气虚血瘀,夹杂湿热的病机特点基本一致。脉象以细脉为主,滑脉,弦脉次之；无力脉较多；说明艾滋病是一种慢性消耗性疾病,兼夹肝郁、痰湿。
三种方法判断证型的研究：
根据临床医生经验判断：以湿热内蕴为主,兼有气郁痰凝、痰热阻肺等证型同时伴有脾气虚弱、气阴两虚、气虚血瘀多见。初步印象以正虚邪实,虚实夹杂。
判别分析判断：以虚证偏多,虚中夹实,例数>10的证型一共有15种,其中12种为虚证。但实邪集中在肝胆湿热,湿热蕴脾,血瘀等证,与医生经验判断一致。
因子分析：从提取的因子看,以脾系为主,涉及肝脾、肺脾以及脾肾,兼有心系症状,初步表明艾滋病病情复杂,涉及多个脏腑。
以上三种方法判断的证型分布情况存在一定的差异,还需要进一步的探讨,但是对艾滋病本质的认识是一致的。
3临床分期与症证分布规律的相关性
3.1症状
无症状期患者以口渴喜饮、乏力、性欲减退、健忘、烦躁等症状为主,出现频率≥50%的症状有5个。AIDS患者以乏力、口渴喜饮、健忘、烦躁、头面浮肿、情绪抑郁、夜尿增多、腰膝酸痛等症状为主,出现频率≥50%的症状有8个。与无症状期相比,检出率≥50%的症状增多,如头面浮肿、夜尿增多、腰膝酸痛等,提示病情由浅入深,随着病情的加重,症状增多。
3.2证型
无症状期单证和复合证比例相差不多,艾滋病期则以复合证为主,有的甚至出现三证以上的复合。三种方法综合分析,无症状期以邪实为主,病位在脾胃,以脾虚为主,少涉及肾系症状；艾滋病期以正虚为主,病位及肝肾,肾气不足,肾阴亏虚表现明显。
4免疫功能与症证型分布规律的相关性
4.1症状
4.1.1 19例CD4+>500/mm3的患者以性欲减退、乏力、健忘、腰膝酸痛、自汗等症状出现较多,频率≥50%的有5个症状,提示病人病情稳定,症状出现较少。
4.1.2 16例CD4+351-500/mm3的患者以乏力、口渴喜饮、烦躁、健忘、小便短黄等症状出现较多,频率≥50%的有15个症状；这部分病人还没有西药干预,随着CD4+细胞的下降,症状增多,本期患者是中医药干预的最佳时期。
4.1.3 38例CD4+201-350/mm3的患者以乏力、口渴喜饮、烦躁、健忘、性欲减退、情绪抑郁等症状出现较多,频率≥50%的有6个症状。这部分病人多数已经开始服用西药,病情得到控制,症状出现较少。
4.1.4 7例CD4+≤200/mm3的患者以乏力、口渴喜饮、口臭、情绪抑郁、腰膝酸痛、头面浮肿等症状出现较多,频率≥50%的有16个症状,乏力检出率达到100%,病位及肾,病情严重。
4.2证型
4.2.1 CD4+细胞计数与气郁痰凝的检出率呈负相关,相关系数-0.326,(P<0.001)；与气阴两虚检出率成正相关,相关系数0.712(P<0.001),脾气虚弱型患者CD4+细胞计数最高(434.75±170.51),肾阴虚型患者CD4+细胞计数最低(331.20±153.94)。初步提示,疾病的早期首先侵犯脾脏,出现正邪斗争的表现,随着疾病的发展进而侵犯肝肾,导致气血阴阳的亏虚。
4.2.2肝胆湿热、胃热炽盛型的患者CD8+细胞计数比较高,均在1000/mm3以上,随着疾病的进展,CD8+细胞计数也呈逐渐下降的趋势。
4.2.3 CD45RA+细胞计数与证型关系与CD4+细胞基本一致,脾气虚弱者CD45RA+计数较高。
5 PRO量表的应用
本研究同步采用“艾滋病四诊信息采集表”和“PRO量表”,由临床医生和患者分别填写,力求能够客观、真实反映患者情况,两个量表之间可以相互验证,互为补充。本次结果显示,PRO量表与艾滋病四诊信息采集表的结果基本相同,多以脾系症状为主,情志方面的改变明显。
结论
北京地区男男性接触者(MSM)艾滋病症状分布规律：以乏力、健忘、烦躁、性欲减退、情绪抑郁、腰膝酸痛等症状为主,与文献研究比较存在一定的差异,发热、咳嗽、腹泻等症状检出率不高,考虑可能与生活条件和感染途径有关,同时提示男男性接触者(MSM)艾滋病主要涉及肝、脾、肾等脏腑,肺系症状相对较少；50%以上的患者有烦躁、情绪抑郁等情志异常表现。
北京地区男男性接触者(MSM)艾滋病证型分布规律：以气虚为内因(检出率41.3%),累及阴阳,兼有精亏,火(热)、湿邪为外因,兼有气滞、痰、饮、瘀血。病位在脾,以肝脾为主,累及肺肾,多以里证为主。舌象：以暗红舌、黄厚腻苔多见,伴有齿痕、瘀斑,与文献报告的艾滋病人气虚血瘀,夹杂湿热的病机特点基本一致。脉象以细脉为主,滑脉,弦脉次之；无力脉较多；说明艾滋病是一种慢性消耗性疾病,兼夹肝郁、痰湿。
Background
The full name of AIDS is acquired immune deficiency syndrome, which is caused by human immunodeficiency virus infection, resulting in immune function partial or complete loss, and followed multi-system, multi-organ, multi-pathogen complex infection (opportunistic infection), and tumors. Clinical manifestations of AIDS can be various. AIDS is a disease with a high mortality and rapid spreading. Although this disease can not be cured, it has become a chronic controllable disease with antiviral therapy used.
We have done a lot of clinical research, and achieved good clinical results in the guidance of conception of holism and treatment based on syndrome differentiation, yet a complete system of treating AIDS in TCM is not formed because of hysteretic work in this area. Researches in symptoms and signs, at present, are limited to clinicians' experience and clinical summary. Because of lack of comparability and objectivity, it is difficult to generalize and evaluate. Therefore, researching characteristic and variation of symptoms and signs of AIDS is a currently pressing problem.
Objective
This research is aims to research distribution of syndrome differentiation of AIDS among MSM in Beijing (including correlation with clinical stage and immune function.
Methods
This study, which is a part of symptoms and signs research of AIDS (major projects of National Science and Technology, project number:2008ZX10005-001),is mainly composed of three parts:The first part introduces literature review, including collection and analysis of literature on HIV/AIDS TCM symptoms and signs. The second part introduces formation of AIDS Four diagnostic Information Form (including formulating content and technology route of symptoms and signs questionnaire of AIDS; constructing frame and item pool of questionnaire; analyzing items, reliability and validity of questionnaire; formulating and implementing interview outline of symptoms and signs of AIDS;) The third part introduce distribution of syndrome differentiation of AIDS among MSM in Beijing (including correlation with clinical stage and immune function; the application of PRO scale in symptoms and signs research;) Summarize as follows:
Results
Part one:Literature review
We retrieved a total of more than 500 AIDS&TCM-related articles. It involves 44 articles of symptoms and signs research, Symptoms recorded in these literatures are few, more over, each article applies different methods of syndrome differentiation, leading to more than 143 kinds of syndrome types are described simultaneously in Literature, only 21 syndrome types are recorded by twice. Syndromes of asymptomatic stage refers to 14, including dampness and heat retention, stagnated qi turning to phlegm retention, qi and yin deficiency, impeded flow of liver-qi lead to qi stagnation. Syndromes of AIDS stage refers to 12, including dampness and heat retention, phlegm heat retention in lung, stagnated qi turning to phlegm retention, phlegm and blood stasis retention. The symptoms focused by all literature are almost the same, some of them has high frequency are listed as follows:fatigue, fever, skin rash, cough, diarrhea et al.
Part two:Development of AIDS Four diagnostic Information Form
This part mainly introduce the formation of AIDS Four diagnostic Information Form, including formulating the planned content, designing technology route, constructing frame and item pool, screening and normalizing items, analyzing reliability and validity of items etc. 1 Formation of AIDS Four diagnostic Information Form
According to the literature, the results of expert consultation, "the guiding principles of Chinese medicine drug", "The People's Republic of China National Standard GB/T 16751.2-1997" and "Diagnostics of Chinese Medicine", we select 61 symptoms. The frame of AIDS Four diagnostic Information Form is initially founded. 2 Expert Consultation:
We consult 57 experts by way of questionnaire, the questions are installed on the basis of syndrome types refined in literature and "three stage of 12 type" of intervention project. By way of semi-quantitative approach, experts judge the importance, specificity and frequency of syndrome types in the process of AIDS. Expert consultation provides important basis for screening items. The syndrome types are sorted according to the following manners:major keywords:arithmetic mean (by descending order), secondary keywords:coefficient of variation (by ascending order), standard deviation(by ascending order). I consider removing "stagnation of qi and phlegm" ranking the final at HIV Positive Stage. Some syndrome types, at times, ranked the final in different literature, In view of the complexity of AIDS stage, "stagnation of qi and phlegm", "phlegm accumulating with stagnation" and "heat invading blood phase" were reserved.
3 Items Standardization
There are three aspects of symptom standardization, including term and meaning of symptoms, quantitation and grading, meaning of syndrome differentiation. Symptom terms and its meaning refer to "The People's Republic of China, Clinical Diagnosis'term for TCM", Total 8 items were splited,10 Normalized, and 4 deleted. Grading of Symptoms were divided into mild, moderate and severe according to symptoms' character, frequency, condition, duration, accompanying symptoms, dependence on drugs and so on. Standardization of meaning of syndrome differentiation:for example, character of bellyache, shape and properties of stool.
4 Reliability and validity
Results showed that reliability and validity is good.
Part three:Distribution of syndrome differentiation of AIDS among MSM in Beijing 1 Distribution of symptoms
Overall impression:main symptoms are fatigue, amnesia, dysphoria, sexual need receding, depression, lumbar genu ache et al, fever, cough and diarrhea have been detected with low level, which is different from literature review, may caused by living condition and transmission routes. The distribution showed MSM HIV/AIDS patients are mainly harmed by liver, spleen, kidney organ in TCM's point of view, while less connected with lung (in TCM). More than 50% patients have disorder in emotion such as dysphoria and depression.
2 Distribution of syndrome differentiation
Overall impression:asthenia of qi is intrinsic factor(41.3%), involving yang-asthenia or yin-asthenia, combining asthenia of essence; pathogenic is external factor, combining stagnation of qi, phlegm, fluid retention, blood stasis; the location of AIDS is spleen, liver and spleen accounts a large proportion, involving lung and kidney; most syndrome differentiation are internal syndrome.darkish red tongue and yellowish greasy tongue coating are common, combining teeth-marked tongue or petechia, roughly the same as reported in the literature. Thin pulse accountss most, slippery pulse and taut pulse take second place, weak pulse is common types. This prove that AIDS is a chronic wasting disease combining stagnation of liver or phlegm-dampness.
Experience of clinical physician:The main syndrome differentiation is internal accumulation of damp-heat, combining stagnation of qi and phlegm, phlegm-heat obstructing lung, asthenia of splenic qi, asthenia of both qi and yin, blood stasis due to asthenia of qi; General characteristics are asthenia of healthy qi and sthenia of pathogenic factors and mixture of cold and heat.
Results of discriminant analysis:asthenia-syndrome is the main type, combining asthenia complicated by sthenia. There are kinds of 15 syndrome differentiations of greater than 10 cases, among those, kinds of 12 are asthenia-syndrome. Sthenia of pathogenic factors fasten on damp-heat in liver and gallbladder, accumulation of damp-heat in spleen and blood stasis etc.
Results of factor Loading Matrix analysis:We totally extracted 19 Factors, which mainly involve spleen, liver complicated spleen, lung complicated spleen, kidney complicated spleen and cardiac, indicating the complexity of AIDS.
Recognition of the roots of HIV/AIDS in TCM is the same, although Distribution of syndrome differentiation acquired by three methods mentioned above has differences, still need to be explored.
3 Correlation between clinical stages and syndrome differentiation
3.1 Symptoms
Patients at asymptomatic stage has main symptoms such as thirsty, fatigue, amnesia, dysphoria, sexual need receding, with 5 symptoms has frequency more than 50%. Patients at AIDS stage has main symptoms such as fatigue, thirsty, amnesia, dysphoria, edema in head, depression, night urine increase, lumbar genu ache, with 8 symptoms has frequency more than 50%, which implicated that disease process go deeper.
3.2 Syndromes
Patients at asymptomatic stage showed almost the same percentage of single syndrome and compound syndrome, while compound syndrome turns to be the main implication at AIDS stage. Location lies spleen at asymptomatic stage, asthenia of spleen is main syndrome differentiation. Location lies liver, spleen and kidney at AIDS Stage, main syndrome differentiation are asthenia of renal qi and insufficiency of renal-yin.
4 Correlation between immunity and syndrome differentiation
4.1 symptoms
4.1.1 19 cases with CD4>500/mm3 has main symptoms such as sexual need receding, fatigue, amnesia, lumbar genu ache, spontaneous sweating,5 symptoms has frequency =50%,which implicated stable disease condition, few symptoms was found.
4.1.2 16 cases with CD4 351-500/mm3 has main symptoms such as fatigue, thirsty, amnesia, dysphoria, short and yellow urine,15 symptoms has frequency=50%, which implicated increased symptoms as decline of CD4.this stage is the best intervention time point.
4.1.3 38 cases with CD4 201-350/mm3 has main symptoms such as fatigue, thirsty, amnesia, dysphoria, short and yellow urine,6 symptoms has frequency=50%, which implicated decreased symptoms as the use of western medicine.
4.1.4 7 cases with CD4≤200/mm3 has main symptoms such as fatigue, thirsty, amnesia, dysphoria, short and yellow urine,16 symptoms has frequency=50%, fatigue was detected 100%, which implicated kidney organ had been affected.
4.2 Syndromes
CD4 counts and stagnation of qi and phlegm are negative correlation. Correlation coefficient:-0.326, (P<0.001); reverse to insufficiency of qi and yin, Correlation coefficient:0.712 (P<0.001), patients with spleen deficiency had high CD4 count (434.75±170.51),patients with kidney yin deficiency had lowest CD4 count (331.20±153.94)
5 Application of PRO scale
PRO scale and AIDS Four diagnostic Information Form was used simultaneously. The former was filled by patients and the latter was filled by clinicians. Two of them can be testified mutually and supplemented each other. The results showed that outcome of the two form are almost the same, which implicated symptoms of spleen (TCM) systems and had obvious change in emotion.
Conclusion
1 Distribution of symptoms:main symptoms are fatigue, amnesia, dysphoria, sexual need receding, depression, lumbar genu ache et al, fever, cough and diarrhea have been detected with low level, which is different from literature review, may caused by living condition and transmission routes. The distribution showed MSM HIV/AIDS patients are mainly harmed by liver, spleen, kidney organ in TCM's point of view, while less connected with lung (in TCM). More than 50% patients have disorder in emotion such as dysphoria and depression.
2 Distribution of syndrome differentiation:asthenia of qi is intrinsic factor(41.3%), involving yang-asthenia or yin-asthenia, combining asthenia of essence; pathogenic is external factor, combining stagnation of qi, phlegm, fluid retention, blood stasis; the location of AIDS is spleen, liver and spleen accounts a large proportion, involving lung and kidney; most syndrome differentiation are internal syndrome.darkish red tongue and yellowish greasy tongue coating are common, combining teeth-marked tongue or petechia, roughly the same as reported in the literature. Thin pulse accountss most, slippery pulse and taut pulse take second place, weak pulse is common types. This prove that AIDS is a chronic wasting disease combining stagnation of liver or phlegm-dampness.
在中医学整体观念和辨证论治的指导下,从90年代开始,进行了中医药治疗艾滋病的临床实践,取得了一定的临床疗效。但是,对于艾滋病中医证候方面的研究起步较晚,不同感染途径、不同地域、不同病期艾滋病患者的中医证候类型和演变规律尚不清楚,证候分类只见于临床医生的一般性临床总结文章中,缺乏大规模、系统的、前瞻性的艾滋病中医证候研究结果。因此,有必要对艾滋病的证候分类和证候演变规律进行研究,为更好地进行艾滋病的中医辨证论证,提高临床疗效奠定基础。
目的
探讨北京地区男男性接触者(MSM)艾滋病症状、证型分布规律以及与临床分期、免疫功能的相关性。
方法
本研究是国家科技重大专项“艾滋病中医证候学研究”(课题号：2008ZX10005-001)的一部分,主要由三部分组成：第一部分文献研究,主要围绕艾滋病的症状、证候进行文献检索、分析、提炼；第二部分主要阐述艾滋病中医四诊信息采集表的研制过程,包括艾滋病四诊信息采集表的内容、结构、条目池的确立；研制艾滋病四诊信息采集表的技术路线以及调查表的维度、信度、效度分析等。第三部分主要阐述北京地区男男性接触者(MSM)艾滋病症证分布规律以及与临床分期、免疫功能的相关性研究,同时探讨PRO量表在症证研究中的应用。现简要阐述如下：
结果
第一部分文献研究
共检索出有关艾滋病的中医研究方面的文献近500余篇。其中涉及中医证候研究的共44篇,所有的文献中有证型记载的文献很少,而且每篇文献的辨证方法不同,有按照五脏分型,有按三焦辨证,结果出现了不同表述的证型143种之多,同时出现两次的表述的只有21种,其中无症状期证型主要涉及14个,湿热内蕴、气郁痰凝、气阴两虚、肝郁气滞等,AIDS期主要涉及12个,湿热内蕴、痰热蕴肺、气郁痰凝、痰瘀互结等。症状条目相对比较集中,所有文献关注的症状基本相同,出现频率比较高的有乏力、发热、皮疹、咳嗽、腹泻等。
第二部分艾滋病四诊信息采集表的研制
本部分主要阐述艾滋病四诊信息采集表的研制过程,包括拟研制的内容及研究的技术路线；艾滋病四诊信息采集表的构架及条目池的构建；条目筛选、规范以及信、效度分析。
1艾滋病四诊信息采集表的构建
根据文献研究结果,以《中药新药指导原则》、《中医诊断学》以及《中华人民共和国国家标准GB/T 16751.2-1997》为依据构建条目,初步形成调查表的框架。
2专家咨询
第一轮专家咨询采用函审与访谈的形式相结合请中国中医科学院从事艾滋病工作10年以上的专家对调查表提出针对调查表的结构,条目设置,提出意见和建议。发出23份问卷,回收22份,少数进行了访谈。专家意见汇总简要如下(详见附件)：根据专家意见条目按照脏腑进行设置,细化条目6条,增加条目5条。
第二轮采用专家问卷形式,备选条目来源于上一轮专家咨询经统计、讨论、整理、规范后保留的症状。根据专家经验判断症状在艾滋病病程中临床出现频率的高低,以及对病程发展的重要性角度考虑,作为筛选条目的依据之一。根据各个症状出现频率以及特异性进行排序,综合考虑删除症状如下：瘀斑、骨蒸。
3条目的规范
对已筛选出的条目进行规范,力求用语的标准化。症状的规范化包括症状术语及其内涵的规范、症状严重程度量化分级的规范、症状辨证学意义的规范三方面的内容。根据《中华人民共和国·中医临床诊疗术语》进行症状术语及其内涵的规范共有8条进行了拆分,10条进行了规范表述,删除了4条。在症状的量化分级方面依据症状的性质特征、出现频率、出现情境、持续时间、伴随的其它症状、对药物的依赖程度、与外界刺激的关系及对日常生活影响程度等项目中的一项或多项划分轻、中、重。症状辨证学意义的规范如：腹痛的性质,大便的性状等。
4信度、效度
内部信度、分半信度以及结构效度均可。
第三部分北京地区男男性接触者(MSM)艾滋病症证分布规律的研究
1症状分布规律
总体印象：以乏力、健忘、烦躁、性欲减退、情绪抑郁、腰膝酸痛等症状为主,与文献研究比较存在一定的差异,发热、咳嗽、腹泻等症状检出率不高,考虑可能与生活条件和感染途径有关,同时提示男男性接触者(MSM)艾滋病主要涉及肝、脾、肾等脏腑,肺系症状相对较少；50%以上的患者有烦躁、情绪抑郁等情志异常表现。
四种途径获得的症状信息的对比研究(文献研究、专家咨询、临床调查、PRO量表)：文献研究与专家咨询的结果比较一致,与临床调查、PRO量表有一定的差别,排名前十位的症状中,本次调查中没有文献以及专家咨询中出现的腹泻、发热、咳嗽等,出现了情志方面的症状。分析原因可能由于文献研究、专家对有偿采供血感染的患者关注比较多,没有针对男男性接触人群的研究。
2证型分布规律
总体印象：以气虚为内因(检出率41.3%),累及阴阳,兼有精亏,火(热)、湿邪为外因,兼有气滞、痰、饮、瘀血。病位在脾,以肝脾为主,累及肺肾,多以里证为主。舌象：以暗红舌、黄厚腻苔多见,伴有齿痕、瘀斑,与文献报告的艾滋病人气虚血瘀,夹杂湿热的病机特点基本一致。脉象以细脉为主,滑脉,弦脉次之；无力脉较多；说明艾滋病是一种慢性消耗性疾病,兼夹肝郁、痰湿。
三种方法判断证型的研究：
根据临床医生经验判断：以湿热内蕴为主,兼有气郁痰凝、痰热阻肺等证型同时伴有脾气虚弱、气阴两虚、气虚血瘀多见。初步印象以正虚邪实,虚实夹杂。
判别分析判断：以虚证偏多,虚中夹实,例数>10的证型一共有15种,其中12种为虚证。但实邪集中在肝胆湿热,湿热蕴脾,血瘀等证,与医生经验判断一致。
因子分析：从提取的因子看,以脾系为主,涉及肝脾、肺脾以及脾肾,兼有心系症状,初步表明艾滋病病情复杂,涉及多个脏腑。
以上三种方法判断的证型分布情况存在一定的差异,还需要进一步的探讨,但是对艾滋病本质的认识是一致的。
3临床分期与症证分布规律的相关性
3.1症状
无症状期患者以口渴喜饮、乏力、性欲减退、健忘、烦躁等症状为主,出现频率≥50%的症状有5个。AIDS患者以乏力、口渴喜饮、健忘、烦躁、头面浮肿、情绪抑郁、夜尿增多、腰膝酸痛等症状为主,出现频率≥50%的症状有8个。与无症状期相比,检出率≥50%的症状增多,如头面浮肿、夜尿增多、腰膝酸痛等,提示病情由浅入深,随着病情的加重,症状增多。
3.2证型
无症状期单证和复合证比例相差不多,艾滋病期则以复合证为主,有的甚至出现三证以上的复合。三种方法综合分析,无症状期以邪实为主,病位在脾胃,以脾虚为主,少涉及肾系症状；艾滋病期以正虚为主,病位及肝肾,肾气不足,肾阴亏虚表现明显。
4免疫功能与症证型分布规律的相关性
4.1症状
4.1.1 19例CD4+>500/mm3的患者以性欲减退、乏力、健忘、腰膝酸痛、自汗等症状出现较多,频率≥50%的有5个症状,提示病人病情稳定,症状出现较少。
4.1.2 16例CD4+351-500/mm3的患者以乏力、口渴喜饮、烦躁、健忘、小便短黄等症状出现较多,频率≥50%的有15个症状；这部分病人还没有西药干预,随着CD4+细胞的下降,症状增多,本期患者是中医药干预的最佳时期。
4.1.3 38例CD4+201-350/mm3的患者以乏力、口渴喜饮、烦躁、健忘、性欲减退、情绪抑郁等症状出现较多,频率≥50%的有6个症状。这部分病人多数已经开始服用西药,病情得到控制,症状出现较少。
4.1.4 7例CD4+≤200/mm3的患者以乏力、口渴喜饮、口臭、情绪抑郁、腰膝酸痛、头面浮肿等症状出现较多,频率≥50%的有16个症状,乏力检出率达到100%,病位及肾,病情严重。
4.2证型
4.2.1 CD4+细胞计数与气郁痰凝的检出率呈负相关,相关系数-0.326,(P<0.001)；与气阴两虚检出率成正相关,相关系数0.712(P<0.001),脾气虚弱型患者CD4+细胞计数最高(434.75±170.51),肾阴虚型患者CD4+细胞计数最低(331.20±153.94)。初步提示,疾病的早期首先侵犯脾脏,出现正邪斗争的表现,随着疾病的发展进而侵犯肝肾,导致气血阴阳的亏虚。
4.2.2肝胆湿热、胃热炽盛型的患者CD8+细胞计数比较高,均在1000/mm3以上,随着疾病的进展,CD8+细胞计数也呈逐渐下降的趋势。
4.2.3 CD45RA+细胞计数与证型关系与CD4+细胞基本一致,脾气虚弱者CD45RA+计数较高。
5 PRO量表的应用
本研究同步采用“艾滋病四诊信息采集表”和“PRO量表”,由临床医生和患者分别填写,力求能够客观、真实反映患者情况,两个量表之间可以相互验证,互为补充。本次结果显示,PRO量表与艾滋病四诊信息采集表的结果基本相同,多以脾系症状为主,情志方面的改变明显。
结论
北京地区男男性接触者(MSM)艾滋病症状分布规律：以乏力、健忘、烦躁、性欲减退、情绪抑郁、腰膝酸痛等症状为主,与文献研究比较存在一定的差异,发热、咳嗽、腹泻等症状检出率不高,考虑可能与生活条件和感染途径有关,同时提示男男性接触者(MSM)艾滋病主要涉及肝、脾、肾等脏腑,肺系症状相对较少；50%以上的患者有烦躁、情绪抑郁等情志异常表现。
北京地区男男性接触者(MSM)艾滋病证型分布规律：以气虚为内因(检出率41.3%),累及阴阳,兼有精亏,火(热)、湿邪为外因,兼有气滞、痰、饮、瘀血。病位在脾,以肝脾为主,累及肺肾,多以里证为主。舌象：以暗红舌、黄厚腻苔多见,伴有齿痕、瘀斑,与文献报告的艾滋病人气虚血瘀,夹杂湿热的病机特点基本一致。脉象以细脉为主,滑脉,弦脉次之；无力脉较多；说明艾滋病是一种慢性消耗性疾病,兼夹肝郁、痰湿。
Background
The full name of AIDS is acquired immune deficiency syndrome, which is caused by human immunodeficiency virus infection, resulting in immune function partial or complete loss, and followed multi-system, multi-organ, multi-pathogen complex infection (opportunistic infection), and tumors. Clinical manifestations of AIDS can be various. AIDS is a disease with a high mortality and rapid spreading. Although this disease can not be cured, it has become a chronic controllable disease with antiviral therapy used.
We have done a lot of clinical research, and achieved good clinical results in the guidance of conception of holism and treatment based on syndrome differentiation, yet a complete system of treating AIDS in TCM is not formed because of hysteretic work in this area. Researches in symptoms and signs, at present, are limited to clinicians' experience and clinical summary. Because of lack of comparability and objectivity, it is difficult to generalize and evaluate. Therefore, researching characteristic and variation of symptoms and signs of AIDS is a currently pressing problem.
Objective
This research is aims to research distribution of syndrome differentiation of AIDS among MSM in Beijing (including correlation with clinical stage and immune function.
Methods
This study, which is a part of symptoms and signs research of AIDS (major projects of National Science and Technology, project number:2008ZX10005-001),is mainly composed of three parts:The first part introduces literature review, including collection and analysis of literature on HIV/AIDS TCM symptoms and signs. The second part introduces formation of AIDS Four diagnostic Information Form (including formulating content and technology route of symptoms and signs questionnaire of AIDS; constructing frame and item pool of questionnaire; analyzing items, reliability and validity of questionnaire; formulating and implementing interview outline of symptoms and signs of AIDS;) The third part introduce distribution of syndrome differentiation of AIDS among MSM in Beijing (including correlation with clinical stage and immune function; the application of PRO scale in symptoms and signs research;) Summarize as follows:
Results
Part one:Literature review
We retrieved a total of more than 500 AIDS&TCM-related articles. It involves 44 articles of symptoms and signs research, Symptoms recorded in these literatures are few, more over, each article applies different methods of syndrome differentiation, leading to more than 143 kinds of syndrome types are described simultaneously in Literature, only 21 syndrome types are recorded by twice. Syndromes of asymptomatic stage refers to 14, including dampness and heat retention, stagnated qi turning to phlegm retention, qi and yin deficiency, impeded flow of liver-qi lead to qi stagnation. Syndromes of AIDS stage refers to 12, including dampness and heat retention, phlegm heat retention in lung, stagnated qi turning to phlegm retention, phlegm and blood stasis retention. The symptoms focused by all literature are almost the same, some of them has high frequency are listed as follows:fatigue, fever, skin rash, cough, diarrhea et al.
Part two:Development of AIDS Four diagnostic Information Form
This part mainly introduce the formation of AIDS Four diagnostic Information Form, including formulating the planned content, designing technology route, constructing frame and item pool, screening and normalizing items, analyzing reliability and validity of items etc. 1 Formation of AIDS Four diagnostic Information Form
According to the literature, the results of expert consultation, "the guiding principles of Chinese medicine drug", "The People's Republic of China National Standard GB/T 16751.2-1997" and "Diagnostics of Chinese Medicine", we select 61 symptoms. The frame of AIDS Four diagnostic Information Form is initially founded. 2 Expert Consultation:
We consult 57 experts by way of questionnaire, the questions are installed on the basis of syndrome types refined in literature and "three stage of 12 type" of intervention project. By way of semi-quantitative approach, experts judge the importance, specificity and frequency of syndrome types in the process of AIDS. Expert consultation provides important basis for screening items. The syndrome types are sorted according to the following manners:major keywords:arithmetic mean (by descending order), secondary keywords:coefficient of variation (by ascending order), standard deviation(by ascending order). I consider removing "stagnation of qi and phlegm" ranking the final at HIV Positive Stage. Some syndrome types, at times, ranked the final in different literature, In view of the complexity of AIDS stage, "stagnation of qi and phlegm", "phlegm accumulating with stagnation" and "heat invading blood phase" were reserved.
3 Items Standardization
There are three aspects of symptom standardization, including term and meaning of symptoms, quantitation and grading, meaning of syndrome differentiation. Symptom terms and its meaning refer to "The People's Republic of China, Clinical Diagnosis'term for TCM", Total 8 items were splited,10 Normalized, and 4 deleted. Grading of Symptoms were divided into mild, moderate and severe according to symptoms' character, frequency, condition, duration, accompanying symptoms, dependence on drugs and so on. Standardization of meaning of syndrome differentiation:for example, character of bellyache, shape and properties of stool.
4 Reliability and validity
Results showed that reliability and validity is good.
Part three:Distribution of syndrome differentiation of AIDS among MSM in Beijing 1 Distribution of symptoms
Overall impression:main symptoms are fatigue, amnesia, dysphoria, sexual need receding, depression, lumbar genu ache et al, fever, cough and diarrhea have been detected with low level, which is different from literature review, may caused by living condition and transmission routes. The distribution showed MSM HIV/AIDS patients are mainly harmed by liver, spleen, kidney organ in TCM's point of view, while less connected with lung (in TCM). More than 50% patients have disorder in emotion such as dysphoria and depression.
2 Distribution of syndrome differentiation
Overall impression:asthenia of qi is intrinsic factor(41.3%), involving yang-asthenia or yin-asthenia, combining asthenia of essence; pathogenic is external factor, combining stagnation of qi, phlegm, fluid retention, blood stasis; the location of AIDS is spleen, liver and spleen accounts a large proportion, involving lung and kidney; most syndrome differentiation are internal syndrome.darkish red tongue and yellowish greasy tongue coating are common, combining teeth-marked tongue or petechia, roughly the same as reported in the literature. Thin pulse accountss most, slippery pulse and taut pulse take second place, weak pulse is common types. This prove that AIDS is a chronic wasting disease combining stagnation of liver or phlegm-dampness.
Experience of clinical physician:The main syndrome differentiation is internal accumulation of damp-heat, combining stagnation of qi and phlegm, phlegm-heat obstructing lung, asthenia of splenic qi, asthenia of both qi and yin, blood stasis due to asthenia of qi; General characteristics are asthenia of healthy qi and sthenia of pathogenic factors and mixture of cold and heat.
Results of discriminant analysis:asthenia-syndrome is the main type, combining asthenia complicated by sthenia. There are kinds of 15 syndrome differentiations of greater than 10 cases, among those, kinds of 12 are asthenia-syndrome. Sthenia of pathogenic factors fasten on damp-heat in liver and gallbladder, accumulation of damp-heat in spleen and blood stasis etc.
Results of factor Loading Matrix analysis:We totally extracted 19 Factors, which mainly involve spleen, liver complicated spleen, lung complicated spleen, kidney complicated spleen and cardiac, indicating the complexity of AIDS.
Recognition of the roots of HIV/AIDS in TCM is the same, although Distribution of syndrome differentiation acquired by three methods mentioned above has differences, still need to be explored.
3 Correlation between clinical stages and syndrome differentiation
3.1 Symptoms
Patients at asymptomatic stage has main symptoms such as thirsty, fatigue, amnesia, dysphoria, sexual need receding, with 5 symptoms has frequency more than 50%. Patients at AIDS stage has main symptoms such as fatigue, thirsty, amnesia, dysphoria, edema in head, depression, night urine increase, lumbar genu ache, with 8 symptoms has frequency more than 50%, which implicated that disease process go deeper.
3.2 Syndromes
Patients at asymptomatic stage showed almost the same percentage of single syndrome and compound syndrome, while compound syndrome turns to be the main implication at AIDS stage. Location lies spleen at asymptomatic stage, asthenia of spleen is main syndrome differentiation. Location lies liver, spleen and kidney at AIDS Stage, main syndrome differentiation are asthenia of renal qi and insufficiency of renal-yin.
4 Correlation between immunity and syndrome differentiation
4.1 symptoms
4.1.1 19 cases with CD4>500/mm3 has main symptoms such as sexual need receding, fatigue, amnesia, lumbar genu ache, spontaneous sweating,5 symptoms has frequency =50%,which implicated stable disease condition, few symptoms was found.
4.1.2 16 cases with CD4 351-500/mm3 has main symptoms such as fatigue, thirsty, amnesia, dysphoria, short and yellow urine,15 symptoms has frequency=50%, which implicated increased symptoms as decline of CD4.this stage is the best intervention time point.
4.1.3 38 cases with CD4 201-350/mm3 has main symptoms such as fatigue, thirsty, amnesia, dysphoria, short and yellow urine,6 symptoms has frequency=50%, which implicated decreased symptoms as the use of western medicine.
4.1.4 7 cases with CD4≤200/mm3 has main symptoms such as fatigue, thirsty, amnesia, dysphoria, short and yellow urine,16 symptoms has frequency=50%, fatigue was detected 100%, which implicated kidney organ had been affected.
4.2 Syndromes
CD4 counts and stagnation of qi and phlegm are negative correlation. Correlation coefficient:-0.326, (P<0.001); reverse to insufficiency of qi and yin, Correlation coefficient:0.712 (P<0.001), patients with spleen deficiency had high CD4 count (434.75±170.51),patients with kidney yin deficiency had lowest CD4 count (331.20±153.94)
5 Application of PRO scale
PRO scale and AIDS Four diagnostic Information Form was used simultaneously. The former was filled by patients and the latter was filled by clinicians. Two of them can be testified mutually and supplemented each other. The results showed that outcome of the two form are almost the same, which implicated symptoms of spleen (TCM) systems and had obvious change in emotion.
Conclusion
1 Distribution of symptoms:main symptoms are fatigue, amnesia, dysphoria, sexual need receding, depression, lumbar genu ache et al, fever, cough and diarrhea have been detected with low level, which is different from literature review, may caused by living condition and transmission routes. The distribution showed MSM HIV/AIDS patients are mainly harmed by liver, spleen, kidney organ in TCM's point of view, while less connected with lung (in TCM). More than 50% patients have disorder in emotion such as dysphoria and depression.
2 Distribution of syndrome differentiation:asthenia of qi is intrinsic factor(41.3%), involving yang-asthenia or yin-asthenia, combining asthenia of essence; pathogenic is external factor, combining stagnation of qi, phlegm, fluid retention, blood stasis; the location of AIDS is spleen, liver and spleen accounts a large proportion, involving lung and kidney; most syndrome differentiation are internal syndrome.darkish red tongue and yellowish greasy tongue coating are common, combining teeth-marked tongue or petechia, roughly the same as reported in the literature. Thin pulse accountss most, slippery pulse and taut pulse take second place, weak pulse is common types. This prove that AIDS is a chronic wasting disease combining stagnation of liver or phlegm-dampness.
引文
[1]何颖.浅析艾滋病的病因病机.湖北中医杂志,2002：24(6)：11
[2]李崇忠等.中医药治疗艾滋病理论的建立和临证应用.实用中医内科杂志,2002：16(2)：62-63
[3]徐志明等.对艾滋病的探讨.云南中医学院学报,2000；23(4)：12-14
[4]李崇忠等.中医药治疗艾滋病理论的建立与临床应用.实用中医内科杂志,2002：16(2)：62-65
[5]徐志明等.对艾滋病的探讨.云南中医学院学报,2000；23(4)：12-14
[6]尤松鑫.艾滋病中医证治概述.江苏中医,1999；20(3)：3-5
[7]陈可冀.中医药治疗艾滋病的临床观察.《AIDS与中医》研讨会论文集,1989年7月
[8]黄柄山.中医药治疗艾滋病.黑龙江科技出版社,1990,12：27
[9]吴伯平 中医对艾滋病的认识中西医结合杂志,1991,(3)：37-38。
[10]苏诚炼 中医药试治艾滋病30例临床报告 中医杂志,1990,(3)：27-29；
[11]赵树珍 艾滋病中医证治探讨浙江中医杂志,1989,(10)：435-438。
[12]王树 在澳大利亚用中医药治疗艾滋病的体会与研讨,天津中医,2000,(1)：1：
[13]吕维柏 八五攻关课题中医治疗艾滋病临床总结 艾滋病人的希望 19；
[14]王健等 中医药治疗艾滋病的现状与思考 中国中医药信息杂志 2001；8(12)：8
[15]姚乃礼 中医证候鉴别诊断学(再版) 人民卫生出版社2002,9 456-462
[16]崔金方.天津中医.1989,(11),37
[17]李国勤.艾滋病中医辨治体会.江苏中医,1994；15(2)：53-55
[18]Lu Weibo, et al. Clinical Observation on ZY-1 in Treating 52 HIV-infected Patients Ⅺ International Conference on AIDS/Vancouver/96. Th. B.4111
[19]关崇芬,吴小闲,卢耀增.中研号方治疗猴爱滋病模型的实验研究,中国中医药信息杂志,1995,2(5)：42.
[20]关崇芬,王健,徐淑玲 中研2号治疗HIV/AIDS的临床和实验研究中国中西医结合杂志2003年第23卷第7期494-497
[21]吕维柏 第12届世界艾滋病大会传统医学进展介绍 中国性病艾滋病防治1998年第4卷第6期；182
[22]WANGJian, YANG Fengzhen, ZHAO Min Randomized Double2blinded and Controlled Clinical Trial on Treatment of HIV/AIDS by Zhongyan-4(中研4 号)Chin J Integr Med 2006 Mar;12 (1):6-11
[23]黄卫平,吕维柏,等.艾通治疗艾滋病病毒感染者22例临床观察,中医杂志,1999,40(10)：606.
[24]危剑安,孙利民,陈宇霞 艾灵颗粒治疗国内HIV／AIDS患者104例临床研究河南中医学院学报 2006年7月第4期4-6
[25]徐立然 益爱康胶囊治疗HIV病毒感染和艾滋病(AIDS)160例临床研究河南中医学院学报 2005年3月第2期4-6
[26]田圣志,田圣勋,王汴新 田氏免疫激发剂治疗HIV／AIDS99例临床疗效分析河南中医学院学报 2007年3月第2期3-5
[27]彭勃, 王丹妮 扶正排毒片Ⅱ号治疗无症状HIV感染65例临床观察 中医药学刊2006年10月第24卷。1781-1783
[28]吕维柏,王健,李建生 金龙胶囊治疗HIV感染者20例初步报告中国艾滋病性病2004年2月第10卷第1期18-19
[29]王小平,蔡蕊 艾乃吉系列颗粒治疗HIV／AIDS 106例临床观察北京中医药大学学报第29卷第6期2006年6月426-428
[30]吕维柏等.中医治疗研究艾滋病实践论文汇编第一辑人民卫生出版社,第一版1992；10 [17]吕维柏.克艾可治疗艾滋病毒感染者60例.中国中西医结合杂志,1993：13(6)
[31]郭会军,刘学伟,王丹妮 爱康1号治疗艾滋病相关综合征疗效观察河南中医学院学报005年11月第6期6-7
[32]田中伟,宋向凤,冯捷 中药复方普乐康治疗HIV／AIDS的临床研究时珍国医国药2005年第16卷第4期344-346
[33]兰金初,李德益,阴忠起 三归片治疗艾滋病临床研究河南中医学院学报2005年1月第1期11-12
[34]吴维萍 朱琳,聂勇 灭艾灵汤剂治疗早中期艾滋病70例 中医研究2004年12月第17卷第6期30
[35]王健,刘颖,潘维新SHJSB治疗HIV／IDS患者临床总结中国中医基础医学杂志2004年第10卷第11期46-48
[36]张妍玲.双黄连粉针剂治疗艾滋病的临床观察,山西医科大学学 报,1999,30(2)：177.
[37]吕维柏.新世纪康保治疗43例艾滋病病人的临床报告,中国性病艾滋病防治,2000,6(3)：168.
[38]莫以贤 中药克艾特胶囊治疗HIV／AIDS14例的临床研究首都医药 2003年第12期40-42
[39]许淑琴,卓展雷,张安荣 艾复康胶囊治疗20例HIV感染者半年临床观察总结中国中医基础医学杂志2006年第12卷第10期784
[40]段萍,杨云松,张春等 康爱保生胶囊治疗艾滋病25例临床观察云南中医中药杂志2006年第27卷第6期19
[41]朱炳发等.中药复方-抗AIDSⅠ号.中国实验临床免疫学杂志,1993,5(4)：40-43
[42]黄柄山.中医药治疗艾滋病临床研究.内部资料
[43]黄芪苓对HIV感染有效.中药事业报.1999-1-6(1)
[44]黎明,吴照运,梁兵 复方三黄散颗粒治疗艾滋病41例报告中国艾滋病性病2006年2月第12卷第1期21-23
[45]时丹 乾坤宁片抗HIV／AIDS的随机双盲安慰剂对照临床研究 中医药学刊2003年9月第21卷第9期1472-1474
[46]田圣志.爱可扶正片治疗艾滋病99例临床疗效分析.中国艾滋病药物治疗研讨会资料汇编[C],2001,9：160-166.
[47]郑友文,皮国华.中草药“再生丹”对HIV感染者的疗效观察[J].中华实验和临床病毒杂志,1999,19(3)：291-294.
[48]杨文雄,XQ 9302中药制剂对艾滋病疗效的初步研究,上海中医药杂志,1999,(1)：4-8.
[49]刘继武.云南省德宏州找到一种治疗艾滋病苗头的药物[J]医学信息,1994,(4)：15-16.
[50]李晖,魏芸.生命泉流浸膏抗HSV—的体外实验研究[J].上海中医药杂志,1999,(7)：6-8
[51]张可.金黄胶囊(金黄口服液)治疗HIV／AIDS10例分析[A]第一届全国中西医结合防治艾滋病学术研讨会论文汇编北京：2003,4：59
[52]张位峡,胡庆和 红毛五加多糖对机体免疫功能的影响[J]中药材,1994, 17(5)：36-38.
[53]黄尧洲,张往峡.红毛五加多糖治疗艾滋病13例临床观察[J].中国中医药信息杂志,1998,5(10)：32.
[54]刘国,张莅峡,黄卫平,等.健脾益肾为主治疗晚期艾滋病38例[J].中医杂志,2000,41(3)：186-186.
[55]王融冰,王晓静,王玉光 健脾益气法治疗艾滋病38例临床观察北京中医2007年1月第26卷第1期9-11
[56]张清奇,孟军礼,郭会军 从脾论治HIV/AIDS患者67例临床观察河南中医学院学报2007年5月第3期1-2
[57]梁杰,王婷,王从亮等 益气养阴、解毒清热法治疗艾滋病的临床研究云南中医中药杂志2007年第28卷第3期8-9
[58]苗芊 益气解毒法治疗艾滋病123例临床观察北京中医药大学学报(中医临床版)2006年11月13(6)43-44
[59]韩桂华.中医药治疗艾滋病60例临床观察[J]中医杂志,2004,45(7)：515-516
[60]王健,刘颖,邹雯等 艾宁颗粒联合HAART治疗100例HIV/AIDS病人的临床观察中国艾滋病性病 2008年4月第14卷101-107
[61]Sishi Fang, Jian Wang, Wenao Huang Effect of medicine of Aining Granule on human liver cytochrome P4501A2,2D6 and 3A4by using pooled human liver microsomes and replataable cryopreserved human primary hepatocytes.Drug Metabolism Review2006(38)57-58
[62]赵红心,张福杰,郜桂菊 国产抗逆转录病毒药物联合中药新血片治疗HIV/AIDS患者24周临床研究中国艾滋病性病 2006年8月第12卷第4期297-299
[63]马伯艳,符林春,蔡卫平 艾可清胶囊联合高效抗病毒逆转录疗法治疗艾滋病临床观察 广州中医药大学学报2007年It月第2,4卷第6期466-467
[64]杨新勇,冀爱英,郭长河 益艾康胶囊治疗HIV/AIDS50例临床分析河南中医学院学报2007年7月第4期6-7
[65]姚文虎,赵伟,吴引伟 复方甘草酸苷辅助治疗艾滋病临床研究河南中医学院学报2006年3月第2期4-5
[66]孟坤,吴葵生,杜式群等HAART联合中药喘可治注射液治疗3例艾滋病临床 观察中华中医药杂志(原中国医药学报)2007年第22卷第5期331-333
[67]李秀惠,胡建华,刘翠娥等 中西医结合治疗85例艾滋病患者临床疗效观察北京中医2007年1月第26卷第1期11-12
[68]危剑安,宋春鑫,陈宇霞 中西医结合治疗HIV／AIDS8例临床分析天津中医药006年a月第23卷第2期123-125
[69]刘鸿雁,蒋士卿,裴俊文 精元康胶囊对艾滋病HAART疗法致骨髓抑制35例的临床观察河南中医学院学报2007年7月第4期4-5
[70]张明利,徐立然,张世玺 小半夏加茯苓汤治疗艾滋病HAART疗法致消化道反应24例中医研究2006年3月第19卷第3期48-49
[71]黄凌,周超杰,梁芳林 当归芍药散治疗艾滋病HAART疗法肝功能损害48例中医研究 2007年8月 第20卷 第8期55-56
[1]伍传仁.中国男男同性恋的研究现状.实用预防医学2009年6月 第16卷第3期985-986
[2]季建林,储展明.认知行为疗法治疗同性恋[J].中国心理卫生杂志,1994,3132.
[3]许新东.关于同性恋的综述[A]1见中国性学会编1性与健康[M].第一版.北京：中国人口出版社,1997130-34.
[4]许毅.男性同性恋生理心理特征研究[A].见中国性学会编.性与健康[M].第一版.北京：中国人口出版社,1997.91-93.
[5]陈培明.同性恋、性病与健康教育[J].中国皮肤性病学杂志2003,17(1)：62.
[6]谷渊.沈阳市男同性恋者性病艾滋病相关KABP分析[J].中国公共卫生,2004,20(5)：375.
[1]FDA. Guidance for industry-patient-reported outcome measures:use in medical product development to support labeling claims, draft guidance. Health QualLife,2006,4:79.
[2]刘凤斌.中医临床疗效评价量表实施设想.中国中医药报,2003-03-17(2).
[3]U. S. Department of Health and Human Services FDA Center for Drug Evaluation and Research, U. S. Department of Health and Human Services FDA Center for Biologics Evaluation and Research, U. S. Department of Health and Human Services FDA Center for Devices and Radiological Health. Guidance for industry:patient-reported outcome measures:use in medical product development to support labeling claims:draft guidance. Health Qual Life Outcomes.2006; 4:79.
[4]Lee P. Dear eDiary - more reliable, and less costly, elect ronic patient diaries are gaining favor. Pharm Exec.2005; (6):20223.
[2]李崇忠等.中医药治疗艾滋病理论的建立和临证应用.实用中医内科杂志,2002：16(2)：62-63
[3]徐志明等.对艾滋病的探讨.云南中医学院学报,2000；23(4)：12-14
[4]李崇忠等.中医药治疗艾滋病理论的建立与临床应用.实用中医内科杂志,2002：16(2)：62-65
[5]徐志明等.对艾滋病的探讨.云南中医学院学报,2000；23(4)：12-14
[6]尤松鑫.艾滋病中医证治概述.江苏中医,1999；20(3)：3-5
[7]陈可冀.中医药治疗艾滋病的临床观察.《AIDS与中医》研讨会论文集,1989年7月
[8]黄柄山.中医药治疗艾滋病.黑龙江科技出版社,1990,12：27
[9]吴伯平 中医对艾滋病的认识中西医结合杂志,1991,(3)：37-38。
[10]苏诚炼 中医药试治艾滋病30例临床报告 中医杂志,1990,(3)：27-29；
[11]赵树珍 艾滋病中医证治探讨浙江中医杂志,1989,(10)：435-438。
[12]王树 在澳大利亚用中医药治疗艾滋病的体会与研讨,天津中医,2000,(1)：1：
[13]吕维柏 八五攻关课题中医治疗艾滋病临床总结 艾滋病人的希望 19；
[14]王健等 中医药治疗艾滋病的现状与思考 中国中医药信息杂志 2001；8(12)：8
[15]姚乃礼 中医证候鉴别诊断学(再版) 人民卫生出版社2002,9 456-462
[16]崔金方.天津中医.1989,(11),37
[17]李国勤.艾滋病中医辨治体会.江苏中医,1994；15(2)：53-55
[18]Lu Weibo, et al. Clinical Observation on ZY-1 in Treating 52 HIV-infected Patients Ⅺ International Conference on AIDS/Vancouver/96. Th. B.4111
[19]关崇芬,吴小闲,卢耀增.中研号方治疗猴爱滋病模型的实验研究,中国中医药信息杂志,1995,2(5)：42.
[20]关崇芬,王健,徐淑玲 中研2号治疗HIV/AIDS的临床和实验研究中国中西医结合杂志2003年第23卷第7期494-497
[21]吕维柏 第12届世界艾滋病大会传统医学进展介绍 中国性病艾滋病防治1998年第4卷第6期；182
[22]WANGJian, YANG Fengzhen, ZHAO Min Randomized Double2blinded and Controlled Clinical Trial on Treatment of HIV/AIDS by Zhongyan-4(中研4 号)Chin J Integr Med 2006 Mar;12 (1):6-11
[23]黄卫平,吕维柏,等.艾通治疗艾滋病病毒感染者22例临床观察,中医杂志,1999,40(10)：606.
[24]危剑安,孙利民,陈宇霞 艾灵颗粒治疗国内HIV／AIDS患者104例临床研究河南中医学院学报 2006年7月第4期4-6
[25]徐立然 益爱康胶囊治疗HIV病毒感染和艾滋病(AIDS)160例临床研究河南中医学院学报 2005年3月第2期4-6
[26]田圣志,田圣勋,王汴新 田氏免疫激发剂治疗HIV／AIDS99例临床疗效分析河南中医学院学报 2007年3月第2期3-5
[27]彭勃, 王丹妮 扶正排毒片Ⅱ号治疗无症状HIV感染65例临床观察 中医药学刊2006年10月第24卷。1781-1783
[28]吕维柏,王健,李建生 金龙胶囊治疗HIV感染者20例初步报告中国艾滋病性病2004年2月第10卷第1期18-19
[29]王小平,蔡蕊 艾乃吉系列颗粒治疗HIV／AIDS 106例临床观察北京中医药大学学报第29卷第6期2006年6月426-428
[30]吕维柏等.中医治疗研究艾滋病实践论文汇编第一辑人民卫生出版社,第一版1992；10 [17]吕维柏.克艾可治疗艾滋病毒感染者60例.中国中西医结合杂志,1993：13(6)
[31]郭会军,刘学伟,王丹妮 爱康1号治疗艾滋病相关综合征疗效观察河南中医学院学报005年11月第6期6-7
[32]田中伟,宋向凤,冯捷 中药复方普乐康治疗HIV／AIDS的临床研究时珍国医国药2005年第16卷第4期344-346
[33]兰金初,李德益,阴忠起 三归片治疗艾滋病临床研究河南中医学院学报2005年1月第1期11-12
[34]吴维萍 朱琳,聂勇 灭艾灵汤剂治疗早中期艾滋病70例 中医研究2004年12月第17卷第6期30
[35]王健,刘颖,潘维新SHJSB治疗HIV／IDS患者临床总结中国中医基础医学杂志2004年第10卷第11期46-48
[36]张妍玲.双黄连粉针剂治疗艾滋病的临床观察,山西医科大学学 报,1999,30(2)：177.
[37]吕维柏.新世纪康保治疗43例艾滋病病人的临床报告,中国性病艾滋病防治,2000,6(3)：168.
[38]莫以贤 中药克艾特胶囊治疗HIV／AIDS14例的临床研究首都医药 2003年第12期40-42
[39]许淑琴,卓展雷,张安荣 艾复康胶囊治疗20例HIV感染者半年临床观察总结中国中医基础医学杂志2006年第12卷第10期784
[40]段萍,杨云松,张春等 康爱保生胶囊治疗艾滋病25例临床观察云南中医中药杂志2006年第27卷第6期19
[41]朱炳发等.中药复方-抗AIDSⅠ号.中国实验临床免疫学杂志,1993,5(4)：40-43
[42]黄柄山.中医药治疗艾滋病临床研究.内部资料
[43]黄芪苓对HIV感染有效.中药事业报.1999-1-6(1)
[44]黎明,吴照运,梁兵 复方三黄散颗粒治疗艾滋病41例报告中国艾滋病性病2006年2月第12卷第1期21-23
[45]时丹 乾坤宁片抗HIV／AIDS的随机双盲安慰剂对照临床研究 中医药学刊2003年9月第21卷第9期1472-1474
[46]田圣志.爱可扶正片治疗艾滋病99例临床疗效分析.中国艾滋病药物治疗研讨会资料汇编[C],2001,9：160-166.
[47]郑友文,皮国华.中草药“再生丹”对HIV感染者的疗效观察[J].中华实验和临床病毒杂志,1999,19(3)：291-294.
[48]杨文雄,XQ 9302中药制剂对艾滋病疗效的初步研究,上海中医药杂志,1999,(1)：4-8.
[49]刘继武.云南省德宏州找到一种治疗艾滋病苗头的药物[J]医学信息,1994,(4)：15-16.
[50]李晖,魏芸.生命泉流浸膏抗HSV—的体外实验研究[J].上海中医药杂志,1999,(7)：6-8
[51]张可.金黄胶囊(金黄口服液)治疗HIV／AIDS10例分析[A]第一届全国中西医结合防治艾滋病学术研讨会论文汇编北京：2003,4：59
[52]张位峡,胡庆和 红毛五加多糖对机体免疫功能的影响[J]中药材,1994, 17(5)：36-38.
[53]黄尧洲,张往峡.红毛五加多糖治疗艾滋病13例临床观察[J].中国中医药信息杂志,1998,5(10)：32.
[54]刘国,张莅峡,黄卫平,等.健脾益肾为主治疗晚期艾滋病38例[J].中医杂志,2000,41(3)：186-186.
[55]王融冰,王晓静,王玉光 健脾益气法治疗艾滋病38例临床观察北京中医2007年1月第26卷第1期9-11
[56]张清奇,孟军礼,郭会军 从脾论治HIV/AIDS患者67例临床观察河南中医学院学报2007年5月第3期1-2
[57]梁杰,王婷,王从亮等 益气养阴、解毒清热法治疗艾滋病的临床研究云南中医中药杂志2007年第28卷第3期8-9
[58]苗芊 益气解毒法治疗艾滋病123例临床观察北京中医药大学学报(中医临床版)2006年11月13(6)43-44
[59]韩桂华.中医药治疗艾滋病60例临床观察[J]中医杂志,2004,45(7)：515-516
[60]王健,刘颖,邹雯等 艾宁颗粒联合HAART治疗100例HIV/AIDS病人的临床观察中国艾滋病性病 2008年4月第14卷101-107
[61]Sishi Fang, Jian Wang, Wenao Huang Effect of medicine of Aining Granule on human liver cytochrome P4501A2,2D6 and 3A4by using pooled human liver microsomes and replataable cryopreserved human primary hepatocytes.Drug Metabolism Review2006(38)57-58
[62]赵红心,张福杰,郜桂菊 国产抗逆转录病毒药物联合中药新血片治疗HIV/AIDS患者24周临床研究中国艾滋病性病 2006年8月第12卷第4期297-299
[63]马伯艳,符林春,蔡卫平 艾可清胶囊联合高效抗病毒逆转录疗法治疗艾滋病临床观察 广州中医药大学学报2007年It月第2,4卷第6期466-467
[64]杨新勇,冀爱英,郭长河 益艾康胶囊治疗HIV/AIDS50例临床分析河南中医学院学报2007年7月第4期6-7
[65]姚文虎,赵伟,吴引伟 复方甘草酸苷辅助治疗艾滋病临床研究河南中医学院学报2006年3月第2期4-5
[66]孟坤,吴葵生,杜式群等HAART联合中药喘可治注射液治疗3例艾滋病临床 观察中华中医药杂志(原中国医药学报)2007年第22卷第5期331-333
[67]李秀惠,胡建华,刘翠娥等 中西医结合治疗85例艾滋病患者临床疗效观察北京中医2007年1月第26卷第1期11-12
[68]危剑安,宋春鑫,陈宇霞 中西医结合治疗HIV／AIDS8例临床分析天津中医药006年a月第23卷第2期123-125
[69]刘鸿雁,蒋士卿,裴俊文 精元康胶囊对艾滋病HAART疗法致骨髓抑制35例的临床观察河南中医学院学报2007年7月第4期4-5
[70]张明利,徐立然,张世玺 小半夏加茯苓汤治疗艾滋病HAART疗法致消化道反应24例中医研究2006年3月第19卷第3期48-49
[71]黄凌,周超杰,梁芳林 当归芍药散治疗艾滋病HAART疗法肝功能损害48例中医研究 2007年8月 第20卷 第8期55-56
[1]伍传仁.中国男男同性恋的研究现状.实用预防医学2009年6月 第16卷第3期985-986
[2]季建林,储展明.认知行为疗法治疗同性恋[J].中国心理卫生杂志,1994,3132.
[3]许新东.关于同性恋的综述[A]1见中国性学会编1性与健康[M].第一版.北京：中国人口出版社,1997130-34.
[4]许毅.男性同性恋生理心理特征研究[A].见中国性学会编.性与健康[M].第一版.北京：中国人口出版社,1997.91-93.
[5]陈培明.同性恋、性病与健康教育[J].中国皮肤性病学杂志2003,17(1)：62.
[6]谷渊.沈阳市男同性恋者性病艾滋病相关KABP分析[J].中国公共卫生,2004,20(5)：375.
[1]FDA. Guidance for industry-patient-reported outcome measures:use in medical product development to support labeling claims, draft guidance. Health QualLife,2006,4:79.
[2]刘凤斌.中医临床疗效评价量表实施设想.中国中医药报,2003-03-17(2).
[3]U. S. Department of Health and Human Services FDA Center for Drug Evaluation and Research, U. S. Department of Health and Human Services FDA Center for Biologics Evaluation and Research, U. S. Department of Health and Human Services FDA Center for Devices and Radiological Health. Guidance for industry:patient-reported outcome measures:use in medical product development to support labeling claims:draft guidance. Health Qual Life Outcomes.2006; 4:79.
[4]Lee P. Dear eDiary - more reliable, and less costly, elect ronic patient diaries are gaining favor. Pharm Exec.2005; (6):20223.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |