缺血性中风病证候诊断量表研究
|
摘要
目的：中医证候标准化、客观化研究的一项重要内容就是证候诊断量表的研究。典型代表是基于计量诊断理论的计量诊断表格，主要用于对目标定性或者无序分类，其目的是建立中医诊断金标准，从而使中医药更容易被世界人民所接受。本次研究的目的是以病证结合为主要指导思想，针对缺血性中风病恢复期痰瘀互结兼气虚证病人以及缺血性中风病恢复期痰瘀互结兼阴虚证病人，在中医理论的指导下初步构建缺血性中风病·恢复期·痰瘀互结兼气虚证、缺血性中风病·恢复期·痰瘀互结兼阴虚证证候诊断量表，通过预调查初步考评上述量表敏感度和特异度，并确定其最佳诊断临界值，以期使辨证简单化、可量化、可操作，并为缺血性中风病恢复期患者研究提供有效诊断工具。
材料与方法：
1.首先成立研究工作组，研究工作组由核心小组和议题小组构成。核心小组以临床医生、证候诊断量表专家及临床流行病学专家为主体，负责具体的研究工作；议题小组成员包括循证医学专家、脑血管病专家、神经内科临床医师、统计学专家、缺血性中风病痰瘀互结兼气虚（或兼阴虚）的患者等组成，负责条目的提出。
2.以证素为核心进行证候规范
证候辨证量表要以辨别证素为主要目标，通过内科书收集、文献整理、临床调查获取缺血性中风病的症状描述，遵循科技术语的命名原则规范各症状名词，依据《中医症状鉴别诊断学》及逻辑学划分，结合专家意见确定术语定义，明确症状间的逻辑关系，建立症状间的概念体系，确定各症状术语在缺血性中风病恢复期的定义。
3.形成条目池，确定条目的形式及回答选项
通过文献回顾、教材梳理、标准收集、临床流调、专家讨论确立条目池，参考课题组前期冠心病辨证规范研究的成果，确立中风病痰瘀互结兼气虚（或兼阴虚）的共性和特异性的症状指证。基于相关文献研究，初步建立的条目池要求条目尽量全面。
4.缺血性中风病恢复期痰瘀互结兼气虚证（或兼阴虚证）证候诊断量表的性能评价
4.1研究对象选择标准
诊断标准：符合西医疾病诊断标准：依据1995年中华医学会制定的《各类脑血管病诊断要点》中动脉粥样硬化性脑梗塞诊断标准，腔隙性脑梗塞诊断标准；同时符合中医疾病诊断标准：参照1995年国家中医药管理局脑病急症科研协作组起草制订的《中风病诊断与疗效评定标准》(试行)。具备《中风病诊断与疗效评定标准》(试行)2个主症以上，或1个主症2个次症，结合起病、诱因、先兆症状、年龄即可确诊；不具备上述条件，结合影像学检查结果亦可确诊。
纳入标准：符合动脉粥样硬化性脑梗塞或腔隙性脑梗塞诊断标准；符合中医缺血性中风病恢复期痰瘀互结兼气虚证诊断标准（或符合中医缺血性中风病恢复期痰瘀互结兼阴虚证诊断标准）；发病第3周至发病6个月的患者；NIHSS积分≥5分者；35岁＜年龄＜85岁；患者本人及家属自愿签署知情同意书。
排除标准：意识状态为昏睡、昏迷的患者；非动脉粥样硬化性脑梗塞（如心源性栓塞、易凝状态、动脉炎、脑肿瘤、脑外伤、脑寄生虫病、代谢障碍引起的卒中）；脑出血、蛛网膜下腔出血、短暂性脑缺血发作（TIA）;不符合入选标准者。
4.2调查方法
选择缺血性中风病·恢复期·痰瘀互结兼气虚证（或兼阴虚）患者，在获得知情同意的基础上，对患者进行调查。
采用横断面调查方法：以缺血性中风病·恢复期痰瘀互结兼气虚证（或兼阴虚证）患者，采用横断面调查，在全国15家医院，对患者进行信息采集，采集的信息包括一般资料、中医诊断、西医诊断、与疾病相关的危险因素、生命体征理化检查、缺血性中风病·恢复期·痰瘀互结兼气虚证（或兼阴虚证）证候诊断量表。
4.3信息采集时间及采集内容：
入组时：试验组及对照组需采集患者的信息有：一般资料、中医诊断、西医诊断、生命体征、与疾病相关危险因素、理化检查、缺血性中风病·恢复期·痰瘀互结兼气虚证（或兼阴虚证）证候诊断量表。
重测：试验组每个证型的20%病例由各分中心两名研究者在30-50分钟内对同一患者进行缺血性中风病·恢复期·痰瘀互结兼气虚证证候诊断量表采集。
研究者选择：研究者为15家分中心从事中医或中西医结合神经内科及康复专业的医师。
5.数据管理
5.1信息采集表填写
信息采集表由临床研究人员填写。临床研究人员应确保将数据准确、完整、及时地记录于信息采集表，同时保存原始病例，完成的信息采集表由分中心临床负责人及监查员审查后，移交本次研究的数据管理员。
5.2数据录入与管理工作
数据录入与管理工作由统计单位的数据管理人员专门负责。数据管理员应用计算机软件编制数据录入程序，为了保证数据录入的准确性，采取双人双次背对背录入方法，并对于不一致的数据进行溯源和校对。
5.3数据审核与锁定
研究结束后，由临床研究人员、数据管理人员、统计分析人员对已建立的数据库进行审核，确认研究数据集和统计分析计划书后对数据库进行锁定。
结果：
1.临床数据描述性统计纳入中风病·恢复期·痰瘀互结兼气虚证患者共1144例。其中男629例，女515例，年龄35～85岁，平均年龄（62.56±9.96）岁。纳入中风病·恢复期·痰瘀互结兼阴虚证患者共472例。其中男246例，女226例，年龄35～85岁，平均年龄（62.88±10.62）岁。
2.证候要素筛选
2.1逐步回归法检验每个条目p值是否小于0.01。结果显示每个条目均为0.00小于0.01，没有条目被删除。
2.2如果条目的出现频率不足1%，则删除该条目，结果各条目出现频率均大于1%，没有条目被删除。
2.3证候要素诊断量表条目筛选结果
2.3.1中风病·恢复期·痰瘀互结兼气虚证各证候要素分别保留条目数为：痰证条目11条，血瘀证条目9条，气虚证条目9条。
2.3.2中风病·恢复期·痰瘀互结兼阴虚证各证候要素分别保留条目数为：痰证条目11条，血瘀证条目9条，阴虚证条目15条。
3.缺血性中风证候要素诊断量表的形成
一份好的证候诊断量表只有具有良好的性能，调查结果才能有良好的内在真实性和外部客观真实性，才能应用于临床评价。证候诊断量表的性能评价包括条目分析、敏感度评价和特异度评价。证候诊断，在特异度、敏感度和判断准确率方面较为可靠。
2.缺血性中风证候要素诊断量表适合于对缺血性中风病恢复期痰瘀互结兼阴虚证证候诊断，在特异度、敏感度和判断准确率方面较为可靠。
结论：
1证候诊断量表能反映缺血性中风病痰瘀互结兼气虚证证候诊断标准
缺血性中风病痰瘀互结兼气虚证证候诊断量表，经大样本量、多中心进行临床信息采集，体现了多中心、大样本量的概念。经过统计学分析，发现缺血性中风病痰瘀互结兼气虚证证候诊断量表的敏感度和特异度结果理想，说明该证候诊断量表能反映缺血性中风病痰瘀互结兼气虚证证候诊断标准。
2证候诊断量表能反映缺血性中风病痰瘀互结兼阴虚证证候诊断标准
缺血性中风病痰瘀互结兼阴虚证证候诊断量表，经大样本量、多中心进行临床信息采集，体现了多中心、大样本量的概念。经过统计学分析，发现缺血性中风病痰瘀互结兼阴虚证证候诊断量表的敏感度和特异度结果理想，说明该证候诊断量表能反映缺血性中风病痰瘀互结兼阴虚证证候诊断标准。
Purpose:A major content of the standardization and objectification study of the traditional Chinese medicine (TCM) syndrome is the study of syndrome diagnostic scale. Typical representative is quantitative diagnosis form based on the quantitative diagnosis theory, which is mainly used for the object qualitative or disordered classification to establish the gold standard of TCM diagnosis, so that TCM could be more likely to be accepted by the people of the world. The purpose of this study is to establish syndrome diagnostic scale about the pattern of stasis-phlegm complicated with deficiency of Qi and the pattern of stasis-phlegm complicated with deficiency of Yin in recovery phase of ischemic apoplexia based on the guiding ideology of the combination of disease and pattern, and to determine the best diagnostic critical value, sensitivity and specific degrees through the preliminary appraisal the scale in the preliminary investigation for simplifying, quantifying and operating the scale. Then, an effective diagnostic tool could be provided for investigating the recovery phase of ischemic apoplexia.
Materials and Methods:
1. To establish the research group which is composed of the core team and issues team.
The core team is mainly constituted with the clinical doctors, syndrome diagnostic scale experts and clinical epidemiological experts who are responsible for the specific research work; Issues team members includes evidence-based medical experts, cerebrovascular disease experts, neurology department clinical physicians, statistics experts and the patients of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin) in the recovery phase who are responsible for proposing entry.
2. To establish the syndrome standard which taking the syndrome factor as the core
Symptoms and signs differentiating scale should take the Syndrome factors differentiation as the main goal. We obtained the symptoms description of ischemic apoplexia through the medical books collection, the literature sorting and clinical investigation, standardized the symptom naming following the scientific and technological terms naming principles, determine the term definition and cleared logical relations between symptoms on the basis of TCM symptoms differential diagnostics and logic division and combined with expert advice, established the concept system among symptoms, and defined symptoms terms in ischemic apoplexia in the recovery phase.
3. Form entry pool and determine the form and answer options of entry
To establish entry pool through the literature review, teaching material carding, standard collection, clinical flow adjustment and expert discussion; to establish symptom indication of the generality and specificity of ischemic apoplexia diseases with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin) in recovery phase referring to the earlier research results of the coronary artery disease differentiation standard research. Based on the literature research, item pool established preliminarily requires comprehensive entries as far as possible.
4. Performance evaluation of syndrome diagnostic scale of ischemic apoplexia diseases with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin) in recovery phase
4.1selection criteria of research object
Diagnosis standard:conform to the western medicine disease diagnosis standard: according to atherosclerotic cerebral infarction diagnosis standards in all kinds of cerebrovascular disease diagnosis points formulated by the Chinese medical association in1995; At the same time comform to the TCM disease diagnosis standard:refer to the apoplexia diagnosis and curative effect evaluation standard "(for trial implementation) drafted by the national administration of TCM encephalopathy emergency research group in1995. Meet more than two primary symptoms, or one primary symptom and two secondary symptoms in the apoplexia diagnosis and curative effect evaluation standard, combined with onset, incentive, premonitory symptoms, age, it could be diagnosed; If do not have the above conditions, combined with imaging examination results, it also could be diagnosed.
Inclusion criteria:accord with atherosclerotic cerebral infarction or lacunar cerebral infarction diagnosis standards; conform to TCM ischemic apoplexia diseases with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin) in recovery phase; The patients were attacked by the diseases for3-6weeks; NIHSS score≥5;35 Exclusion criteria:Patients whose consciousness is stupor or coma; Non atherosclerotic cerebral infarction (such as cardiac embolism, hypercoagulable state, arteritis, brain tumor, brain trauma, brain parasites disease, stroke caused by metabolic disorder); Cerebral hemorrhage, subarachnoid hemorrhage, transient ischemic attack (TIA); Patients who do not conform to the inclusion criteria.
4.2investigation method
Choose ischemic apoplexia patients with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin) in recovery phase; investigate the patients on the basis of obtaining informed consent.
Using cross-sectional survey methods:ischemic apoplexia patients with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin) from15hospitals were investigated by cross-sectional survey. We collected patients' information including general information, TCM diagnosis, and western medicine diagnosis, and related risk factors, vital signs, physical and chemical inspection, syndrome diagnostic scale of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin).
4.3information acquisition time and content:
When in groups:information of patients in experimental group and control group which should be collected are general data, TCM diagnosis, western medicine diagnosis, vital signs, and related risk factors, physical and chemical inspection, syndrome diagnostic scale of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin).
Resurvey:20%patients with every patten in treatment group were carried on collection of syndrome diagnostic scale of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin)
Choosing researchers:the researchers are neurology department doctors and rehabilitation doctors engaging TCM or combine TCM and western medicine from15sub-centers.
5. Data management
5.1fill in information collection table
Information collection tables were filled by clinical research researchers. Clinical researchers should ensure that the data is accurate, complete and timely records in information collection table; at the same time, they should keep original cases. Completed information collection tables were reviewed by head of sub-centers, and handed over to the research data administrator.
5.2data entry and management
Data management personnel from the statistics units are responsible for data entry and management work. Data administrator formatted data entry procedures by applying computer software. In order to ensure the accuracy of the data entry, we adopted two researchers and twice back to back input method, and trace to the source and proofread inconsistent data.
5.3data review and lock
At the end of the study, the clinical research personnel, data administrators, statistics analysis personnel reviewed the established database, confirm the research data set and statistical analysis plans, and then lock the database.
Results
1. Clinical data descriptive statistics
1144patients were brought into the group of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi in recovery phase, including629male cases and515female cases, aged from35to85years old. The average age is62.56±9.96.
472patients were brought into the group of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Yin in recovery phase, including246male cases and226female cases, aged from35to85years old. The average age is62.88±10.62.
2. Screening syndrome factors
2.1P value of every entry is tested whether less than0.01by stepwise regression method. Results show that p values in each entry are0.00which is less than0.01, so no entry was deleted.
2.2If the frequency of occurrence is less than1%, then delete the entry. The results showed that the frequency of occurrence were greater than1%, no entry was deleted.
In the syndrome information of1144ischemic apoplexia patients with pattern of stasis-phlegm complicated with deficiency of Qi in recovery phase, the syndrome factors frequency see table1.
2.3Entry screening results of factors diagnosis scale
2.3.1Reserved entry number of syndrome factors of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi was:11phlegm syndrome entries,9blood stasis syndrome entries,9deficiency of Qi syndrome entries.
2.3.2Reserved entry number of syndrome factors of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi was:11phlegm syndrome entries,9blood stasis syndrome entries,15deficiency of Yin syndrome entries.
3. Formation of Ischemic apoplexia syndrome factors diagnosis scale
A good syndrome diagnostic scale should have good performance, then the results of the survey could have good inner authenticity and external objective reality, could be applied to clinical evaluation. Performance evaluations of Syndrome diagnostic scale include entry analysis, sensitivity evaluation and specificity evaluation.
3.1We used ROC curve to analyze the syndrome factors of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi. The analysis results are shown in this figure:
3.2We used ROC curve to analyze the syndrome factors of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Yin. The analysis results are shown in this figure:
To sum up:
1. Ischemic apoplexia syndrome factors diagnosis scale is suitable for the syndrome diagnosis of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi. The scale is more reliable in evaluation specificity, sensitivity and accuracy.
2. Ischemic apoplexia syndrome factors diagnosis scale is suitable for the syndrome diagnosis of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Yin. The scale is more reliable in evaluation specificity, sensitivity and accuracy.
Conclusions:
1syndrome diagnostic scale could reflect the syndrome diagnostic standard of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi.
Syndrome diagnostic scale of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi reflected the multicenter, large sample size concept through the large sample size and multicenter clinical information acquisition. After statistics analysis, it is found that Syndrome diagnostic scale of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi have ideal sensitivity and specificity, suggesting that syndrome diagnostic scale could reflect the diagnostic standard of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi.
2syndrome diagnostic scale could reflect the syndrome diagnostic standard of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Yin.
Syndrome diagnostic scale of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Yin reflected the multicenter, large sample size concept through the large sample size and multicenter clinical information acquisition. After statistics analysis, it is found that Syndrome diagnostic scale of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi have ideal sensitivity and specificity, suggesting that syndrome diagnostic scale could reflect the diagnostic standard of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Yin.
材料与方法：
1.首先成立研究工作组，研究工作组由核心小组和议题小组构成。核心小组以临床医生、证候诊断量表专家及临床流行病学专家为主体，负责具体的研究工作；议题小组成员包括循证医学专家、脑血管病专家、神经内科临床医师、统计学专家、缺血性中风病痰瘀互结兼气虚（或兼阴虚）的患者等组成，负责条目的提出。
2.以证素为核心进行证候规范
证候辨证量表要以辨别证素为主要目标，通过内科书收集、文献整理、临床调查获取缺血性中风病的症状描述，遵循科技术语的命名原则规范各症状名词，依据《中医症状鉴别诊断学》及逻辑学划分，结合专家意见确定术语定义，明确症状间的逻辑关系，建立症状间的概念体系，确定各症状术语在缺血性中风病恢复期的定义。
3.形成条目池，确定条目的形式及回答选项
通过文献回顾、教材梳理、标准收集、临床流调、专家讨论确立条目池，参考课题组前期冠心病辨证规范研究的成果，确立中风病痰瘀互结兼气虚（或兼阴虚）的共性和特异性的症状指证。基于相关文献研究，初步建立的条目池要求条目尽量全面。
4.缺血性中风病恢复期痰瘀互结兼气虚证（或兼阴虚证）证候诊断量表的性能评价
4.1研究对象选择标准
诊断标准：符合西医疾病诊断标准：依据1995年中华医学会制定的《各类脑血管病诊断要点》中动脉粥样硬化性脑梗塞诊断标准，腔隙性脑梗塞诊断标准；同时符合中医疾病诊断标准：参照1995年国家中医药管理局脑病急症科研协作组起草制订的《中风病诊断与疗效评定标准》(试行)。具备《中风病诊断与疗效评定标准》(试行)2个主症以上，或1个主症2个次症，结合起病、诱因、先兆症状、年龄即可确诊；不具备上述条件，结合影像学检查结果亦可确诊。
纳入标准：符合动脉粥样硬化性脑梗塞或腔隙性脑梗塞诊断标准；符合中医缺血性中风病恢复期痰瘀互结兼气虚证诊断标准（或符合中医缺血性中风病恢复期痰瘀互结兼阴虚证诊断标准）；发病第3周至发病6个月的患者；NIHSS积分≥5分者；35岁＜年龄＜85岁；患者本人及家属自愿签署知情同意书。
排除标准：意识状态为昏睡、昏迷的患者；非动脉粥样硬化性脑梗塞（如心源性栓塞、易凝状态、动脉炎、脑肿瘤、脑外伤、脑寄生虫病、代谢障碍引起的卒中）；脑出血、蛛网膜下腔出血、短暂性脑缺血发作（TIA）;不符合入选标准者。
4.2调查方法
选择缺血性中风病·恢复期·痰瘀互结兼气虚证（或兼阴虚）患者，在获得知情同意的基础上，对患者进行调查。
采用横断面调查方法：以缺血性中风病·恢复期痰瘀互结兼气虚证（或兼阴虚证）患者，采用横断面调查，在全国15家医院，对患者进行信息采集，采集的信息包括一般资料、中医诊断、西医诊断、与疾病相关的危险因素、生命体征理化检查、缺血性中风病·恢复期·痰瘀互结兼气虚证（或兼阴虚证）证候诊断量表。
4.3信息采集时间及采集内容：
入组时：试验组及对照组需采集患者的信息有：一般资料、中医诊断、西医诊断、生命体征、与疾病相关危险因素、理化检查、缺血性中风病·恢复期·痰瘀互结兼气虚证（或兼阴虚证）证候诊断量表。
重测：试验组每个证型的20%病例由各分中心两名研究者在30-50分钟内对同一患者进行缺血性中风病·恢复期·痰瘀互结兼气虚证证候诊断量表采集。
研究者选择：研究者为15家分中心从事中医或中西医结合神经内科及康复专业的医师。
5.数据管理
5.1信息采集表填写
信息采集表由临床研究人员填写。临床研究人员应确保将数据准确、完整、及时地记录于信息采集表，同时保存原始病例，完成的信息采集表由分中心临床负责人及监查员审查后，移交本次研究的数据管理员。
5.2数据录入与管理工作
数据录入与管理工作由统计单位的数据管理人员专门负责。数据管理员应用计算机软件编制数据录入程序，为了保证数据录入的准确性，采取双人双次背对背录入方法，并对于不一致的数据进行溯源和校对。
5.3数据审核与锁定
研究结束后，由临床研究人员、数据管理人员、统计分析人员对已建立的数据库进行审核，确认研究数据集和统计分析计划书后对数据库进行锁定。
结果：
1.临床数据描述性统计纳入中风病·恢复期·痰瘀互结兼气虚证患者共1144例。其中男629例，女515例，年龄35～85岁，平均年龄（62.56±9.96）岁。纳入中风病·恢复期·痰瘀互结兼阴虚证患者共472例。其中男246例，女226例，年龄35～85岁，平均年龄（62.88±10.62）岁。
2.证候要素筛选
2.1逐步回归法检验每个条目p值是否小于0.01。结果显示每个条目均为0.00小于0.01，没有条目被删除。
2.2如果条目的出现频率不足1%，则删除该条目，结果各条目出现频率均大于1%，没有条目被删除。
2.3证候要素诊断量表条目筛选结果
2.3.1中风病·恢复期·痰瘀互结兼气虚证各证候要素分别保留条目数为：痰证条目11条，血瘀证条目9条，气虚证条目9条。
2.3.2中风病·恢复期·痰瘀互结兼阴虚证各证候要素分别保留条目数为：痰证条目11条，血瘀证条目9条，阴虚证条目15条。
3.缺血性中风证候要素诊断量表的形成
一份好的证候诊断量表只有具有良好的性能，调查结果才能有良好的内在真实性和外部客观真实性，才能应用于临床评价。证候诊断量表的性能评价包括条目分析、敏感度评价和特异度评价。证候诊断，在特异度、敏感度和判断准确率方面较为可靠。
2.缺血性中风证候要素诊断量表适合于对缺血性中风病恢复期痰瘀互结兼阴虚证证候诊断，在特异度、敏感度和判断准确率方面较为可靠。
结论：
1证候诊断量表能反映缺血性中风病痰瘀互结兼气虚证证候诊断标准
缺血性中风病痰瘀互结兼气虚证证候诊断量表，经大样本量、多中心进行临床信息采集，体现了多中心、大样本量的概念。经过统计学分析，发现缺血性中风病痰瘀互结兼气虚证证候诊断量表的敏感度和特异度结果理想，说明该证候诊断量表能反映缺血性中风病痰瘀互结兼气虚证证候诊断标准。
2证候诊断量表能反映缺血性中风病痰瘀互结兼阴虚证证候诊断标准
缺血性中风病痰瘀互结兼阴虚证证候诊断量表，经大样本量、多中心进行临床信息采集，体现了多中心、大样本量的概念。经过统计学分析，发现缺血性中风病痰瘀互结兼阴虚证证候诊断量表的敏感度和特异度结果理想，说明该证候诊断量表能反映缺血性中风病痰瘀互结兼阴虚证证候诊断标准。
Purpose:A major content of the standardization and objectification study of the traditional Chinese medicine (TCM) syndrome is the study of syndrome diagnostic scale. Typical representative is quantitative diagnosis form based on the quantitative diagnosis theory, which is mainly used for the object qualitative or disordered classification to establish the gold standard of TCM diagnosis, so that TCM could be more likely to be accepted by the people of the world. The purpose of this study is to establish syndrome diagnostic scale about the pattern of stasis-phlegm complicated with deficiency of Qi and the pattern of stasis-phlegm complicated with deficiency of Yin in recovery phase of ischemic apoplexia based on the guiding ideology of the combination of disease and pattern, and to determine the best diagnostic critical value, sensitivity and specific degrees through the preliminary appraisal the scale in the preliminary investigation for simplifying, quantifying and operating the scale. Then, an effective diagnostic tool could be provided for investigating the recovery phase of ischemic apoplexia.
Materials and Methods:
1. To establish the research group which is composed of the core team and issues team.
The core team is mainly constituted with the clinical doctors, syndrome diagnostic scale experts and clinical epidemiological experts who are responsible for the specific research work; Issues team members includes evidence-based medical experts, cerebrovascular disease experts, neurology department clinical physicians, statistics experts and the patients of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin) in the recovery phase who are responsible for proposing entry.
2. To establish the syndrome standard which taking the syndrome factor as the core
Symptoms and signs differentiating scale should take the Syndrome factors differentiation as the main goal. We obtained the symptoms description of ischemic apoplexia through the medical books collection, the literature sorting and clinical investigation, standardized the symptom naming following the scientific and technological terms naming principles, determine the term definition and cleared logical relations between symptoms on the basis of TCM symptoms differential diagnostics and logic division and combined with expert advice, established the concept system among symptoms, and defined symptoms terms in ischemic apoplexia in the recovery phase.
3. Form entry pool and determine the form and answer options of entry
To establish entry pool through the literature review, teaching material carding, standard collection, clinical flow adjustment and expert discussion; to establish symptom indication of the generality and specificity of ischemic apoplexia diseases with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin) in recovery phase referring to the earlier research results of the coronary artery disease differentiation standard research. Based on the literature research, item pool established preliminarily requires comprehensive entries as far as possible.
4. Performance evaluation of syndrome diagnostic scale of ischemic apoplexia diseases with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin) in recovery phase
4.1selection criteria of research object
Diagnosis standard:conform to the western medicine disease diagnosis standard: according to atherosclerotic cerebral infarction diagnosis standards in all kinds of cerebrovascular disease diagnosis points formulated by the Chinese medical association in1995; At the same time comform to the TCM disease diagnosis standard:refer to the apoplexia diagnosis and curative effect evaluation standard "(for trial implementation) drafted by the national administration of TCM encephalopathy emergency research group in1995. Meet more than two primary symptoms, or one primary symptom and two secondary symptoms in the apoplexia diagnosis and curative effect evaluation standard, combined with onset, incentive, premonitory symptoms, age, it could be diagnosed; If do not have the above conditions, combined with imaging examination results, it also could be diagnosed.
Inclusion criteria:accord with atherosclerotic cerebral infarction or lacunar cerebral infarction diagnosis standards; conform to TCM ischemic apoplexia diseases with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin) in recovery phase; The patients were attacked by the diseases for3-6weeks; NIHSS score≥5;35
4.2investigation method
Choose ischemic apoplexia patients with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin) in recovery phase; investigate the patients on the basis of obtaining informed consent.
Using cross-sectional survey methods:ischemic apoplexia patients with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin) from15hospitals were investigated by cross-sectional survey. We collected patients' information including general information, TCM diagnosis, and western medicine diagnosis, and related risk factors, vital signs, physical and chemical inspection, syndrome diagnostic scale of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin).
4.3information acquisition time and content:
When in groups:information of patients in experimental group and control group which should be collected are general data, TCM diagnosis, western medicine diagnosis, vital signs, and related risk factors, physical and chemical inspection, syndrome diagnostic scale of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin).
Resurvey:20%patients with every patten in treatment group were carried on collection of syndrome diagnostic scale of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi (or Yin)
Choosing researchers:the researchers are neurology department doctors and rehabilitation doctors engaging TCM or combine TCM and western medicine from15sub-centers.
5. Data management
5.1fill in information collection table
Information collection tables were filled by clinical research researchers. Clinical researchers should ensure that the data is accurate, complete and timely records in information collection table; at the same time, they should keep original cases. Completed information collection tables were reviewed by head of sub-centers, and handed over to the research data administrator.
5.2data entry and management
Data management personnel from the statistics units are responsible for data entry and management work. Data administrator formatted data entry procedures by applying computer software. In order to ensure the accuracy of the data entry, we adopted two researchers and twice back to back input method, and trace to the source and proofread inconsistent data.
5.3data review and lock
At the end of the study, the clinical research personnel, data administrators, statistics analysis personnel reviewed the established database, confirm the research data set and statistical analysis plans, and then lock the database.
Results
1. Clinical data descriptive statistics
1144patients were brought into the group of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi in recovery phase, including629male cases and515female cases, aged from35to85years old. The average age is62.56±9.96.
472patients were brought into the group of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Yin in recovery phase, including246male cases and226female cases, aged from35to85years old. The average age is62.88±10.62.
2. Screening syndrome factors
2.1P value of every entry is tested whether less than0.01by stepwise regression method. Results show that p values in each entry are0.00which is less than0.01, so no entry was deleted.
2.2If the frequency of occurrence is less than1%, then delete the entry. The results showed that the frequency of occurrence were greater than1%, no entry was deleted.
In the syndrome information of1144ischemic apoplexia patients with pattern of stasis-phlegm complicated with deficiency of Qi in recovery phase, the syndrome factors frequency see table1.
2.3Entry screening results of factors diagnosis scale
2.3.1Reserved entry number of syndrome factors of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi was:11phlegm syndrome entries,9blood stasis syndrome entries,9deficiency of Qi syndrome entries.
2.3.2Reserved entry number of syndrome factors of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi was:11phlegm syndrome entries,9blood stasis syndrome entries,15deficiency of Yin syndrome entries.
3. Formation of Ischemic apoplexia syndrome factors diagnosis scale
A good syndrome diagnostic scale should have good performance, then the results of the survey could have good inner authenticity and external objective reality, could be applied to clinical evaluation. Performance evaluations of Syndrome diagnostic scale include entry analysis, sensitivity evaluation and specificity evaluation.
3.1We used ROC curve to analyze the syndrome factors of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi. The analysis results are shown in this figure:
3.2We used ROC curve to analyze the syndrome factors of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Yin. The analysis results are shown in this figure:
To sum up:
1. Ischemic apoplexia syndrome factors diagnosis scale is suitable for the syndrome diagnosis of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi. The scale is more reliable in evaluation specificity, sensitivity and accuracy.
2. Ischemic apoplexia syndrome factors diagnosis scale is suitable for the syndrome diagnosis of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Yin. The scale is more reliable in evaluation specificity, sensitivity and accuracy.
Conclusions:
1syndrome diagnostic scale could reflect the syndrome diagnostic standard of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi.
Syndrome diagnostic scale of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi reflected the multicenter, large sample size concept through the large sample size and multicenter clinical information acquisition. After statistics analysis, it is found that Syndrome diagnostic scale of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi have ideal sensitivity and specificity, suggesting that syndrome diagnostic scale could reflect the diagnostic standard of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi.
2syndrome diagnostic scale could reflect the syndrome diagnostic standard of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Yin.
Syndrome diagnostic scale of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Yin reflected the multicenter, large sample size concept through the large sample size and multicenter clinical information acquisition. After statistics analysis, it is found that Syndrome diagnostic scale of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Qi have ideal sensitivity and specificity, suggesting that syndrome diagnostic scale could reflect the diagnostic standard of ischemic apoplexia with pattern of stasis-phlegm complicated with deficiency of Yin.
引文
[1]王智民，杜力军，毕开顺.中药药效评价的“水闸门”法.世界科学技术一中医药现代化，2000，2(5):34～38.
[2]吕爱平.中药现代化发展新要求-应重视中药适应症和中药药效评价的研究[J].首都医药，2003，10(3):27～30.
[3] Katherine Gundling. The desktop guide to complementary and Alternative Medicine:An Evidenced-Based Approach. JAMA,2001,286(16):2030.
[4] Diana Brahams. Standard of care for alternative medicine. The Lancet,2000,356(9239):1422.
[5] Jin-Ling Tang, Si-Yan Zhan, Ernst E. review of randomiszed controlled trisalsof traditional Chinese medicine. Btitish Medical Journal1999;319(7203):160～161.
[6] Ernst E. Herbal medicines: where is the evidence? Growing evidence ofeffectiveness in counterbalanced by inadequate regulation. Bretish Medical Journal2000;321(7258):395～396.
[7] Robert Yuan, Yuan Lin. Traditional Chinese medicine: an approach to scientificproof and clinical validation. Pharmacology&Therapeutics2000;86(2):191～198.
[8]Levin JS, Glass TA, Kushi LH,et al. Quantitative methods in research oncomplementary and alternative medicine. A methodological manifesto. NIH Office ofAlternative Medicine[J].Med Care,1997,35(11):1079～1094.
[9]中医现代化科技发展战略研究课题组.中医疗效系统评价体系的研究[J].世界科学技术―中医现代化,2002,4(2):12～14.
[10]赖世隆.中医药临床疗效评价若干关键环节的思考[J].广州中医药大学学报,2002,19(4):245～250.
[11]蒋文跃，黄熙.中医方药作用特点及现代药效评价标准的缺陷[J].中国中西医结合杂志，2003，23(3):222～224.
[12]马堃,李连达.对中药新药临床疗效评价的几点思考[J].中国中药杂志，2004，29(5):489～491.
[13]徐慧,崔蒙.中医临床疗效评价方法的建立[J].中国中医药信息杂志，2008，15(8):9～10.
[14]张军平,吕仕超，朱亚萍，等.病证结合模式下的中医药临床疗效评价着力点.世界科学技术：中医药现代化，2011，13(6):956～959.
[15]张鸣明,李幼平,刘鸣.循证医学的起源和概念.首届亚太地区循证医学研讨会文献集[C].成都:中国循证医学中心,2000年10月.
[16]宋军,陈可冀.中医药临床疗效评价若干问题思考[J].中国中西医结合杂志,2003,23(8):564～565.
[17]徐燕,徐厚谦.用循证医学方法提高中医药临床科研质量[J].甘肃中医学院学报,2003,20(4):20～21.
[18]刘建平.循证医学与中医疗效评价[J].中医杂志,2007,48(1):26～28.
[19]郑海生,徐海春等.浅议循证医学在中医药疗效评价中的应用意义[J].时珍国医国药，2010，21(7)：1794～1795.
[20]刘建平，Heather Mclntosh，林辉.中草药治疗慢性乙型肝炎随机对照试验的系统评价[J].中国循证医学，2001，1(1)：16～24.
[21]刘云霞,工洁贞,庞春坤,等.中草药治疗脂肪肝随机对照试验的系统评价[J].循证医学，2005,5(1):29～32.
[22]庾慧，韩云,许坚，等.中药治疗慢性支气管炎随机对照试验的系统评价[J].中药新药与临床药理，2006,17(6):468～471.
[23]刘宇,莫胜丹,李瑛.中药治疗绝经后骨质疏松症的系统评价[J].海南医学，2005，16(2)：136～137.
[24]向桃,叶学锋,刘琳,等.中药治疗慢性肾小球肾炎系统评价[J].中国中西医结合肾病杂志,2007，8(1)：48～50.
[25]李可建.三七制剂治疗缺血性中风急性期随机对照试验的系统评价[J].临床荟萃，2007，22(1):1～5.
[26]刘昌孝.代谢组学研究有助于中药复杂系统与整体效应的认识.中国天然药物，2009，7(2):81.
[27]Nicholson JK,Lindon JC. Systems biology: metabonomics.Nature,2008,455(7216):1054～1056.
[28]Coen M, Holmes E, Lindon JC,et al． NMR-based metabolic profiling and metabonomieapproaches to problems in molecular toxicology [J]. Chem Res Toxicol,2008,21(1):9～27.
[29] Xu EY, Schaefer WH, Xu Q. Metabolomics in pharmaceutical research and development:metabolites, mechanisms and pathways[J]. Curr opin Drug Discov Devel,2009,12(1):40～52.
[30]王广基,查伟斌,郝海平,等.代谢组学技术在中医药关键科学问题研究中的应用前景分析[J].中国天然药物,2008,6(2):89～97.
[31] Nicho lson JK, Wilson ID. Opinion: understanding ‘global’systems biology:metabonomics and the cont inum of metabolism [J]. Nat Rev Drug Discov,2003,2(8):668～676.
[32]王阶,姚魁武,衷敬柏,等.基于临床流行病学的血瘀证量化计分表研究[J].中医杂志,2008,49(3)，270～272.
[33] Hunt SM, McKenna SP, McEwen J, et al. The Nottingham Health Profile: subjectivehealth status and medical consultations［J］.Soc Sci Med，1981，15(3Pt1):221～229.
[34] Bergner M, Bobbit RA, Pollard WE, et al. The sickness impact profile: validationof a health status measure［J］. Med Care,1976,14(1):57～67.
[35] Kaplan RM, Bush JW, Berry CC. Health status: types of validity and the indexof well-being［J］. Health Serv Res,1976,11(4):478～507.
[36]陈可冀.关于传统中医药临床疗效评价问题[J].中西医结合学报,2005,3(1)：1～2.
[37]赖世隆,胡镜清,郭新峰.循证医学与中医药临床研究［J］.广州中医药大学学报,2000,17(1):18
[38]罗智博,张哲等.以系统论为指导构建中医临床疗效评价指标体系.中华中医药学刊，2008,26(2):257～259.
[39] Croog SH, Levine S, Tests M, et al. The effects of antihypertensive therapyon the quality of life N Engl J Med,1986,314(26):1657～1664.
[40] Ganz PA. Methods of assessing the effect of drug therapy on quality of life.Drug Saf,1990,5(4):233～242.
[41]戴摇霞,郭伟星.老年高血压病肾气亏虚证诊断量表的信度与效度测评[J].时珍国医国药,2010,21(9):2324～2326.
[42]王阶,李军,杨戈.冠心病心绞痛病证结合的证候诊断量表的制定思路与方法[J].世界科学技术一中医药现代化，2007,9(3):13～17．
[43]万霞,陈家旭,胡立胜.围绝经期综合征中医症状学量表信度评价[J].辽宁中医杂志,2009,36(10):1682～1683.
[44]王力宁，蔡晓静，初晓，等.小儿反复呼吸道感染中医证候量表分型与免疫指标相关性的研究[J].广西医科大学学报,2009,26(4):519～522.
[45]史晓,蔡奇文,杜修东,等.原发性骨质疏松症患者中医量表的信度及效度研究[J].中医杂志,2009,50(2):124～126.
[46]林颖娜,王芳,张容瑞,等.中医养生功法对2型糖尿病患者症状自评量表评分的影响[J].中医杂志,2009,50(5):419～421.
[47]刘鲁蓉,李昌吉,龙云芳,等.中医医生职业承诺量表的结构模型评价研究[J].四川大学学报(医学版),2009,40(2):318～321.
[48]李学军,陈志刚.原发性失眠中医证型与焦虑自评量表关系的研究[J].光明中医，2010,25(6):913～915.
[49] The WHOQOL Group. Development of the World Health Organization WHOQOL—BREFquality of life assessment[J]．Psychol Med，1998，28(3)：551～558．
[50]周仲瑛.中医内科学.2版.北京：中国中医药出版社.2007:304
[51]杨宁．周仲瑛从瘀热论治缺血性中风急性期的学术思想[J]．北京中医，2007，26(12)：775．
[52]常富业,王永炎.中风病毒邪论［J］.北京中医药大学学报，2004，27(1)：58～61.
[53]常富业.毒损脉络诠释［J］.北京中医药大学学报，2006，29(11)：729～731.
[54］李澎涛.毒损脑络病机假说的形成及其理论与实践意义［J］.北京中医药大学学报，2002，24(1)：1～6.
[55]王晓宝,张建美,王晓玲.孙立军教授治疗中风病经验[J].中国中医急症，2011，20（11）：1766～1768
[56]张允岭,常富业,王永炎,等.论内毒损伤络脉病因与发病学说的意义[J].北京中医药大学学报,2006,29(8):514～516.
[57]祝维峰,周迎春,冯学功,等.邵念方教授治疗中风病特色浅述[J].中国中医急症,1997,6(6):274～275.
[58]段才萍.活血化瘀治疗脑出血临床观察[J].四川中医,2003,21(4):44～45
[59]郭会军,武吉涛,金杰.郑绍周教授治疗缺血性中风经验[J].新中医,2001,33(6):12～13.
[60]张燕，孙乐球，林海飞．急性脑梗死中医证型与甲状腺激素水平相关性研究[J]．福建中医药，2009，4O(2)：9～10．
[61]田金洲,时晶，倪敬年．脑梗塞患者颈动脉斑块与血瘀证的相关性研究[J]．中华中医药杂志,2007,22(3):149～152．
[62]赵洪鉴,李浩.急性脑卒中病理反射变化的临床分析.华西医学2010,25(5):854～855
[63]李春丽，关春燕，扎西草．脑梗死中医证型与颈动脉粥样硬化的相关性研究[J]．江苏中医药，2010，42(5)：25～26．
[64]张东林，孟庆阳，刘志辉，等．脑梗死不同证型与颈动脉粥样硬化斑块相关性探讨[J]．山东中医药大学学报，2010，34(1)：37～38．
[65]焦劲松,王丽,张永庆,等.垂体卒中的临床与病理.中国医刊，2008,43(2)：46～48
[66]吴宣富,胡顶高.急性缺血性卒中的病理生理学:脑栓塞的新概念.国外医学脑血管疾病分册,1998,6(6)：332～334.
[67] Fukui M，Song JH，Choi J，el a1．Mechanism of glutamate-induced neurotoxicityin HT22mouse hippocampal cells [J]．Eur J Pharmaco1．2009，617(1-3)：1～11.
[68]Leist M, Nicotera P. Apoptosis, excitotoxicity, and neuropathology.Exp Cell Res,1998,239(2):183～201.
[69]Thornberry NA, Lazebnik Y. Caspases: enemies within. Science,1998,281(5381):1312～1316
[70] Namura S, Zhu J, Fink K, et al. Activation and cleavage of caspase3in apoptosisinduced by experimental cerebral ischemia. J Neurosci,1998,18(10):3659～3668.
[71]张伯礼,宋其云,崔秀琼,等.天津地区中医中风病危险因素及证候调查研究.天津中医,2000,17(1):35～37.
[72]温伟伦,睦道顺.中西医结合治疗缺血性中风(痰热内扰型)164例临床观察.新中医，2009，41(2)：47～48.(将这篇文章发给我)
[73]傅振江.活化汤加减合灯盏花注射液治疗缺血性中风疗效观察[J].河北中医,2002,24(6):430
[74]瞿泸.脑力智宝治疗脑梗死后遗症的疗效观察[J].中华现代中西医杂志,2005,3(4):341～342
[75]杜静平,张静.华佗再造丸用于中风恢复期后遗症期的临床观察[J].成都医药,2003,29(3):155
[76]王麟鹏，刘慧林，刘志顺,等.贺氏三通法对缺血性中风患者神经功能缺损的影响：多中心随机对照研究.中国针灸,2006,26(5):309～312
[77]李学国.半夏白术天麻汤加味治疗风痰瘀阻型缺血性中风的疗效观察北京中医，2007，26（5）：287～288.
[78]张牧寒,安邦煌.补肾通脉片治疗肾虚痰癖型中风临床观察[J].中医杂志，1994，35（11）668～670.
[79]张道杰,吴玉生,彭立义,等. SOD、MDA测定对补阳还五汤治疗缺血性中风疗效评估[J].新中医,1996,28(5):59～60.
[80]郭义,张艳军,王秀云,等.手十二井穴刺络放血对中风患者颅内血流动力学影响的观察[J].针灸临床杂志,1995,11(6):21.
[81]马岩,郭义,张艳军,等.手十二井穴刺络放血对实验性脑缺血大鼠缺血组织K+、Na+浓度影响的动态观察[J].中国针灸，1997,17(9):562.
[82]李东晓,卢海燕，李惟国.降纤酶、刺五加联合应用治疗急性脑梗死的疗效观察［J］.中国实用神经疾病杂志,2007,10(3):37～38.
[83]王鲲鹏.低分子肝素治疗进展型中风临床观察[J].航空航天医药，2010，21（1）：77～78.
[84]石学慧,谭涛,李丹丹.侯氏黑散治疗痰瘀阻络型缺血性中风恢复期的临床观察[J].中医药导报,2009,15(3):21～23.
[85]李凤玲.化痰通腑汤灌肠治疗中风病急性期痰热腑实证158例[J].中医杂志,2008，49(7):637.
[86]翟瑞柏.化痰通腑汤治疗中风急性期的临床观察[J].湖北中医杂志,2010，32（1）：41～42.
[87]吕奇玮,李翊锐.平肝化痰通络方治疗风痰瘀阻型中风后遗症疗效观察[J].上海中医药杂志,2010,44(6):53～58.
[88]祝美珍,王琳,吴志敏.清热化瘀Ⅱ号方治疗缺血性中风的临床观察[J].广西中医药，2011，34(5):7～8.
[89]袁学开.三七补阳还五汤治疗中风后遗症35例[J].河南中医,2010,30(2):170～171.
[90]李长聪.通腑化痰活血醒脑汤治疗痰热腑实证中风病中脏腑的临床观察[J].北京中医药，2009,28(9):728～729.
[91]付渊博,邹忆怀,王新志.星蒌通腑汤治疗急性缺血性中风痰热腑实证临床观察[J].中华中医药学刊,2010,28(3):668～670.
[92]王忠.中医中风病证候的多元统计分析[J].中国中西医结志,2003,23(2):106～109.
[93]王进.中风病(非急性期)辨证规律探讨[J].山西中医,1998,14(4):43～44.
[94]周慎,易振佳,赵伍立,等.757例中风后遗症中医证候与中风主症的相关性分析[J].湖南中医药导报,2003,9(8):11～14.
[95]“中风病证候学与临床诊断的研究”科研协作组.《中风病证候诊断标准》的临床验证研究.北京中医药大学学报,1994,17(6):41～43.
[96]李先涛,赖世隆,梁伟雄,等.建立急性缺血性中风气虚血瘀证诊断标准的方法学探讨[J].广州中医药大学学报,2000,17(3):218～222.
[97]国家中医药管理局医政司.中医内科急症诊疗规范·中风病急症诊疗规范.北京大学出版社,1994,9～11.
[98]郭蓉娟,杨云龙,吴燕,等.中风病风火上扰清窍证的证候规范初探[J].北京中医药大学学报,1997,20(4):60～61.
[99]高颖，黄粤，张华，等。应用时序序列探讨缺血性中风急性期证候与OCSP分型的相关性[J].北京中医药大学学报，2010,33(10)，685～694.
[100]梁宝华.脑血管病临床辨证规范化定量化的进一步研究[J].北京中医药大学学报,1997,20(2):47～50.
[101]王玉来.中风急症证候分析[J].中国中医急症,1995,4(2):75～78.
[102]朱文锋.证候辨证量表制定的科学性要求[J].中国中医药信息杂志，2005,12（8）：93～94.
[103]刘强，陈建新，陈静，等．通过动态关联度系数聚堆的临床证候要素提取方法初探［J］．中国中医药信息杂志，2007,14(12):100～102．
[104]赵金铎.中医症状鉴别诊断学[M].北京:人民卫生出版社,1985.
[105]高颖,马斌，刘强,王永炎.缺血性中风证候要素诊断量表编制及方法学探讨[J].中医杂志，2011，52(24)：2097～2101.
[2]吕爱平.中药现代化发展新要求-应重视中药适应症和中药药效评价的研究[J].首都医药，2003，10(3):27～30.
[3] Katherine Gundling. The desktop guide to complementary and Alternative Medicine:An Evidenced-Based Approach. JAMA,2001,286(16):2030.
[4] Diana Brahams. Standard of care for alternative medicine. The Lancet,2000,356(9239):1422.
[5] Jin-Ling Tang, Si-Yan Zhan, Ernst E. review of randomiszed controlled trisalsof traditional Chinese medicine. Btitish Medical Journal1999;319(7203):160～161.
[6] Ernst E. Herbal medicines: where is the evidence? Growing evidence ofeffectiveness in counterbalanced by inadequate regulation. Bretish Medical Journal2000;321(7258):395～396.
[7] Robert Yuan, Yuan Lin. Traditional Chinese medicine: an approach to scientificproof and clinical validation. Pharmacology&Therapeutics2000;86(2):191～198.
[8]Levin JS, Glass TA, Kushi LH,et al. Quantitative methods in research oncomplementary and alternative medicine. A methodological manifesto. NIH Office ofAlternative Medicine[J].Med Care,1997,35(11):1079～1094.
[9]中医现代化科技发展战略研究课题组.中医疗效系统评价体系的研究[J].世界科学技术―中医现代化,2002,4(2):12～14.
[10]赖世隆.中医药临床疗效评价若干关键环节的思考[J].广州中医药大学学报,2002,19(4):245～250.
[11]蒋文跃，黄熙.中医方药作用特点及现代药效评价标准的缺陷[J].中国中西医结合杂志，2003，23(3):222～224.
[12]马堃,李连达.对中药新药临床疗效评价的几点思考[J].中国中药杂志，2004，29(5):489～491.
[13]徐慧,崔蒙.中医临床疗效评价方法的建立[J].中国中医药信息杂志，2008，15(8):9～10.
[14]张军平,吕仕超，朱亚萍，等.病证结合模式下的中医药临床疗效评价着力点.世界科学技术：中医药现代化，2011，13(6):956～959.
[15]张鸣明,李幼平,刘鸣.循证医学的起源和概念.首届亚太地区循证医学研讨会文献集[C].成都:中国循证医学中心,2000年10月.
[16]宋军,陈可冀.中医药临床疗效评价若干问题思考[J].中国中西医结合杂志,2003,23(8):564～565.
[17]徐燕,徐厚谦.用循证医学方法提高中医药临床科研质量[J].甘肃中医学院学报,2003,20(4):20～21.
[18]刘建平.循证医学与中医疗效评价[J].中医杂志,2007,48(1):26～28.
[19]郑海生,徐海春等.浅议循证医学在中医药疗效评价中的应用意义[J].时珍国医国药，2010，21(7)：1794～1795.
[20]刘建平，Heather Mclntosh，林辉.中草药治疗慢性乙型肝炎随机对照试验的系统评价[J].中国循证医学，2001，1(1)：16～24.
[21]刘云霞,工洁贞,庞春坤,等.中草药治疗脂肪肝随机对照试验的系统评价[J].循证医学，2005,5(1):29～32.
[22]庾慧，韩云,许坚，等.中药治疗慢性支气管炎随机对照试验的系统评价[J].中药新药与临床药理，2006,17(6):468～471.
[23]刘宇,莫胜丹,李瑛.中药治疗绝经后骨质疏松症的系统评价[J].海南医学，2005，16(2)：136～137.
[24]向桃,叶学锋,刘琳,等.中药治疗慢性肾小球肾炎系统评价[J].中国中西医结合肾病杂志,2007，8(1)：48～50.
[25]李可建.三七制剂治疗缺血性中风急性期随机对照试验的系统评价[J].临床荟萃，2007，22(1):1～5.
[26]刘昌孝.代谢组学研究有助于中药复杂系统与整体效应的认识.中国天然药物，2009，7(2):81.
[27]Nicholson JK,Lindon JC. Systems biology: metabonomics.Nature,2008,455(7216):1054～1056.
[28]Coen M, Holmes E, Lindon JC,et al． NMR-based metabolic profiling and metabonomieapproaches to problems in molecular toxicology [J]. Chem Res Toxicol,2008,21(1):9～27.
[29] Xu EY, Schaefer WH, Xu Q. Metabolomics in pharmaceutical research and development:metabolites, mechanisms and pathways[J]. Curr opin Drug Discov Devel,2009,12(1):40～52.
[30]王广基,查伟斌,郝海平,等.代谢组学技术在中医药关键科学问题研究中的应用前景分析[J].中国天然药物,2008,6(2):89～97.
[31] Nicho lson JK, Wilson ID. Opinion: understanding ‘global’systems biology:metabonomics and the cont inum of metabolism [J]. Nat Rev Drug Discov,2003,2(8):668～676.
[32]王阶,姚魁武,衷敬柏,等.基于临床流行病学的血瘀证量化计分表研究[J].中医杂志,2008,49(3)，270～272.
[33] Hunt SM, McKenna SP, McEwen J, et al. The Nottingham Health Profile: subjectivehealth status and medical consultations［J］.Soc Sci Med，1981，15(3Pt1):221～229.
[34] Bergner M, Bobbit RA, Pollard WE, et al. The sickness impact profile: validationof a health status measure［J］. Med Care,1976,14(1):57～67.
[35] Kaplan RM, Bush JW, Berry CC. Health status: types of validity and the indexof well-being［J］. Health Serv Res,1976,11(4):478～507.
[36]陈可冀.关于传统中医药临床疗效评价问题[J].中西医结合学报,2005,3(1)：1～2.
[37]赖世隆,胡镜清,郭新峰.循证医学与中医药临床研究［J］.广州中医药大学学报,2000,17(1):18
[38]罗智博,张哲等.以系统论为指导构建中医临床疗效评价指标体系.中华中医药学刊，2008,26(2):257～259.
[39] Croog SH, Levine S, Tests M, et al. The effects of antihypertensive therapyon the quality of life N Engl J Med,1986,314(26):1657～1664.
[40] Ganz PA. Methods of assessing the effect of drug therapy on quality of life.Drug Saf,1990,5(4):233～242.
[41]戴摇霞,郭伟星.老年高血压病肾气亏虚证诊断量表的信度与效度测评[J].时珍国医国药,2010,21(9):2324～2326.
[42]王阶,李军,杨戈.冠心病心绞痛病证结合的证候诊断量表的制定思路与方法[J].世界科学技术一中医药现代化，2007,9(3):13～17．
[43]万霞,陈家旭,胡立胜.围绝经期综合征中医症状学量表信度评价[J].辽宁中医杂志,2009,36(10):1682～1683.
[44]王力宁，蔡晓静，初晓，等.小儿反复呼吸道感染中医证候量表分型与免疫指标相关性的研究[J].广西医科大学学报,2009,26(4):519～522.
[45]史晓,蔡奇文,杜修东,等.原发性骨质疏松症患者中医量表的信度及效度研究[J].中医杂志,2009,50(2):124～126.
[46]林颖娜,王芳,张容瑞,等.中医养生功法对2型糖尿病患者症状自评量表评分的影响[J].中医杂志,2009,50(5):419～421.
[47]刘鲁蓉,李昌吉,龙云芳,等.中医医生职业承诺量表的结构模型评价研究[J].四川大学学报(医学版),2009,40(2):318～321.
[48]李学军,陈志刚.原发性失眠中医证型与焦虑自评量表关系的研究[J].光明中医，2010,25(6):913～915.
[49] The WHOQOL Group. Development of the World Health Organization WHOQOL—BREFquality of life assessment[J]．Psychol Med，1998，28(3)：551～558．
[50]周仲瑛.中医内科学.2版.北京：中国中医药出版社.2007:304
[51]杨宁．周仲瑛从瘀热论治缺血性中风急性期的学术思想[J]．北京中医，2007，26(12)：775．
[52]常富业,王永炎.中风病毒邪论［J］.北京中医药大学学报，2004，27(1)：58～61.
[53]常富业.毒损脉络诠释［J］.北京中医药大学学报，2006，29(11)：729～731.
[54］李澎涛.毒损脑络病机假说的形成及其理论与实践意义［J］.北京中医药大学学报，2002，24(1)：1～6.
[55]王晓宝,张建美,王晓玲.孙立军教授治疗中风病经验[J].中国中医急症，2011，20（11）：1766～1768
[56]张允岭,常富业,王永炎,等.论内毒损伤络脉病因与发病学说的意义[J].北京中医药大学学报,2006,29(8):514～516.
[57]祝维峰,周迎春,冯学功,等.邵念方教授治疗中风病特色浅述[J].中国中医急症,1997,6(6):274～275.
[58]段才萍.活血化瘀治疗脑出血临床观察[J].四川中医,2003,21(4):44～45
[59]郭会军,武吉涛,金杰.郑绍周教授治疗缺血性中风经验[J].新中医,2001,33(6):12～13.
[60]张燕，孙乐球，林海飞．急性脑梗死中医证型与甲状腺激素水平相关性研究[J]．福建中医药，2009，4O(2)：9～10．
[61]田金洲,时晶，倪敬年．脑梗塞患者颈动脉斑块与血瘀证的相关性研究[J]．中华中医药杂志,2007,22(3):149～152．
[62]赵洪鉴,李浩.急性脑卒中病理反射变化的临床分析.华西医学2010,25(5):854～855
[63]李春丽，关春燕，扎西草．脑梗死中医证型与颈动脉粥样硬化的相关性研究[J]．江苏中医药，2010，42(5)：25～26．
[64]张东林，孟庆阳，刘志辉，等．脑梗死不同证型与颈动脉粥样硬化斑块相关性探讨[J]．山东中医药大学学报，2010，34(1)：37～38．
[65]焦劲松,王丽,张永庆,等.垂体卒中的临床与病理.中国医刊，2008,43(2)：46～48
[66]吴宣富,胡顶高.急性缺血性卒中的病理生理学:脑栓塞的新概念.国外医学脑血管疾病分册,1998,6(6)：332～334.
[67] Fukui M，Song JH，Choi J，el a1．Mechanism of glutamate-induced neurotoxicityin HT22mouse hippocampal cells [J]．Eur J Pharmaco1．2009，617(1-3)：1～11.
[68]Leist M, Nicotera P. Apoptosis, excitotoxicity, and neuropathology.Exp Cell Res,1998,239(2):183～201.
[69]Thornberry NA, Lazebnik Y. Caspases: enemies within. Science,1998,281(5381):1312～1316
[70] Namura S, Zhu J, Fink K, et al. Activation and cleavage of caspase3in apoptosisinduced by experimental cerebral ischemia. J Neurosci,1998,18(10):3659～3668.
[71]张伯礼,宋其云,崔秀琼,等.天津地区中医中风病危险因素及证候调查研究.天津中医,2000,17(1):35～37.
[72]温伟伦,睦道顺.中西医结合治疗缺血性中风(痰热内扰型)164例临床观察.新中医，2009，41(2)：47～48.(将这篇文章发给我)
[73]傅振江.活化汤加减合灯盏花注射液治疗缺血性中风疗效观察[J].河北中医,2002,24(6):430
[74]瞿泸.脑力智宝治疗脑梗死后遗症的疗效观察[J].中华现代中西医杂志,2005,3(4):341～342
[75]杜静平,张静.华佗再造丸用于中风恢复期后遗症期的临床观察[J].成都医药,2003,29(3):155
[76]王麟鹏，刘慧林，刘志顺,等.贺氏三通法对缺血性中风患者神经功能缺损的影响：多中心随机对照研究.中国针灸,2006,26(5):309～312
[77]李学国.半夏白术天麻汤加味治疗风痰瘀阻型缺血性中风的疗效观察北京中医，2007，26（5）：287～288.
[78]张牧寒,安邦煌.补肾通脉片治疗肾虚痰癖型中风临床观察[J].中医杂志，1994，35（11）668～670.
[79]张道杰,吴玉生,彭立义,等. SOD、MDA测定对补阳还五汤治疗缺血性中风疗效评估[J].新中医,1996,28(5):59～60.
[80]郭义,张艳军,王秀云,等.手十二井穴刺络放血对中风患者颅内血流动力学影响的观察[J].针灸临床杂志,1995,11(6):21.
[81]马岩,郭义,张艳军,等.手十二井穴刺络放血对实验性脑缺血大鼠缺血组织K+、Na+浓度影响的动态观察[J].中国针灸，1997,17(9):562.
[82]李东晓,卢海燕，李惟国.降纤酶、刺五加联合应用治疗急性脑梗死的疗效观察［J］.中国实用神经疾病杂志,2007,10(3):37～38.
[83]王鲲鹏.低分子肝素治疗进展型中风临床观察[J].航空航天医药，2010，21（1）：77～78.
[84]石学慧,谭涛,李丹丹.侯氏黑散治疗痰瘀阻络型缺血性中风恢复期的临床观察[J].中医药导报,2009,15(3):21～23.
[85]李凤玲.化痰通腑汤灌肠治疗中风病急性期痰热腑实证158例[J].中医杂志,2008，49(7):637.
[86]翟瑞柏.化痰通腑汤治疗中风急性期的临床观察[J].湖北中医杂志,2010，32（1）：41～42.
[87]吕奇玮,李翊锐.平肝化痰通络方治疗风痰瘀阻型中风后遗症疗效观察[J].上海中医药杂志,2010,44(6):53～58.
[88]祝美珍,王琳,吴志敏.清热化瘀Ⅱ号方治疗缺血性中风的临床观察[J].广西中医药，2011，34(5):7～8.
[89]袁学开.三七补阳还五汤治疗中风后遗症35例[J].河南中医,2010,30(2):170～171.
[90]李长聪.通腑化痰活血醒脑汤治疗痰热腑实证中风病中脏腑的临床观察[J].北京中医药，2009,28(9):728～729.
[91]付渊博,邹忆怀,王新志.星蒌通腑汤治疗急性缺血性中风痰热腑实证临床观察[J].中华中医药学刊,2010,28(3):668～670.
[92]王忠.中医中风病证候的多元统计分析[J].中国中西医结志,2003,23(2):106～109.
[93]王进.中风病(非急性期)辨证规律探讨[J].山西中医,1998,14(4):43～44.
[94]周慎,易振佳,赵伍立,等.757例中风后遗症中医证候与中风主症的相关性分析[J].湖南中医药导报,2003,9(8):11～14.
[95]“中风病证候学与临床诊断的研究”科研协作组.《中风病证候诊断标准》的临床验证研究.北京中医药大学学报,1994,17(6):41～43.
[96]李先涛,赖世隆,梁伟雄,等.建立急性缺血性中风气虚血瘀证诊断标准的方法学探讨[J].广州中医药大学学报,2000,17(3):218～222.
[97]国家中医药管理局医政司.中医内科急症诊疗规范·中风病急症诊疗规范.北京大学出版社,1994,9～11.
[98]郭蓉娟,杨云龙,吴燕,等.中风病风火上扰清窍证的证候规范初探[J].北京中医药大学学报,1997,20(4):60～61.
[99]高颖，黄粤，张华，等。应用时序序列探讨缺血性中风急性期证候与OCSP分型的相关性[J].北京中医药大学学报，2010,33(10)，685～694.
[100]梁宝华.脑血管病临床辨证规范化定量化的进一步研究[J].北京中医药大学学报,1997,20(2):47～50.
[101]王玉来.中风急症证候分析[J].中国中医急症,1995,4(2):75～78.
[102]朱文锋.证候辨证量表制定的科学性要求[J].中国中医药信息杂志，2005,12（8）：93～94.
[103]刘强，陈建新，陈静，等．通过动态关联度系数聚堆的临床证候要素提取方法初探［J］．中国中医药信息杂志，2007,14(12):100～102．
[104]赵金铎.中医症状鉴别诊断学[M].北京:人民卫生出版社,1985.
[105]高颖,马斌，刘强,王永炎.缺血性中风证候要素诊断量表编制及方法学探讨[J].中医杂志，2011，52(24)：2097～2101.
© 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 |