出血性中风“瘀热”机元的测量和评价研究
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摘要
目的：本研究基于国医大师周仲瑛教授“审证求机”理论,综合多种辨证方法,建立基于机素-机元的中医病机辨证体系,从而规范和活化中医辨证方法,以期指导临床实践,提高中医临床辨证质量：基于机素-机元的病机创新理论,诠释国医大师周仲瑛教授的瘀热复合病机理论；以出血性中风为疾病切入点,通过专家咨询和临床验证的病证结合研究,建立辨证亚单元-瘀热机元的测量和评价方法,形成出血性中风瘀热机元的特异性测量量表,为以机元为辨证亚单元的客观测量探索可行方法。
方法：本研究以国医大师周仲瑛教授的医案为素材,采用广义字典模型(generalized dictionary model)等数据挖掘方法,结合中医医理分析构建基于机素-机元的中医病机辨证创新体系,基于该体系诠释瘀热复合病机的内涵；在此理论的指导下,以出血性中风为疾病研究切入点,开展病证结合研究,通过文献研究和专家集体讨论的方法,建立瘀热量表表征的条目池和测量的指标体系,应用专家咨询的方法,进一步补充、修订和完善测量表征；采用临床流行病学前瞻纵向调查设计和多水平结构方程模型等复杂数据的分析方法验证瘀热存在的客观性,考核出血性中风瘀热机元特异性疾病测量量表的信度和效度等参数。本研究也是国家重点基础研究发展计划(973)课题-“瘀热”病因在内科难治病发病中的机制及其分子基础研究的一部分(课题编号：2006CB504807)。
结果：通过数据挖掘方法,本研究建立了基于机素-机元的中医病机辨证体系,机元可以看成独立的病机单元或病理单元,以此为中医辨证的核心或亚单元,临床复杂的证候可以看成是机元及其相关表征的组合。瘀热机元是瘀机元和热机元的胶结合和、非线性组合,具有不可分性。通过专家咨询研究,确定了瘀热机元全病域量表的测量维度,分为血热、血瘀、出血、神志四个方面,可以通过59条目的表征信息来反应,其中血热征有21个条目,血瘀征有15个条目,出血征有17个条目,神志征有6个条目；出血性中风瘀热机元的量表分为血热、血瘀、神志三个维度,共32条目,其中血热征有19个条目,血瘀征有7个条目,神志征有6个条目,全病域测量量表专家咨询的Cronbach's Alpha信度为0.924。通过临床验证,在专家经验的基础上,结合各宏观表征的测量信度,进一步精选了瘀热表征信息,最终筛选出25个测量信度较高,专家诊断意义较大的25个表征进入多水平结构方程模型：模型拟合结果：Full Information ML Chi-Square=6402.47554 (P<0.001), df=565, RMSEA(近似误差均方根)=0.099816,表明数据模型拟合外在指数尚可,结构方程模型显示了二阶潜在变量瘀热(ξ)和一阶潜在变量(η)征象维度间的权重关系,显示了瘀热与血热(实热、虚热)、血瘀及神志变化的关系,其中神志征对瘀热贡献较大,这反应了出血性中风急性期以神志征为特征表现的疾病特点；模式内在质量考核有25个显性指标达统计学显著性；表明量表内在适配指标是可接受的。根据专家咨询和临床验证,修改和完善了出血性中风瘀热机元的测量量表,根据因子得分回归方程初步建立了瘀热机元的定量测量方法。
结论：中医多种辨证方法具有明显的规律性,病机分析是其灵魂。以机素-机元为核心的病机元素和病机单元,能更加灵活和简约地解析中医病机辨证规律；机素揭示了病机构成的基本元素,机元则是辨证的独立病理单元或亚单元,后者也是构成中医病机的低维度、不可分、可实证的病理单元和药物作用的明确靶点,机元之间可以互相演变和转化。临床上以机元为辨证亚单元的规范和测量,更能反映审证求机和审机论治的特点和优势。“瘀热”是不可拆分的复合病机单元,由瘀和热两个机素紧密构成,可以看成“瘀”和“热”两个机元非线性交互组合而成,在其致病过程中,不仅有瘀和热的共同参与,而且瘀和热之间胶结合和,有其内在的因果关联。因此瘀热实为独立的机元或病理单元,是基于“瘀”和“热”两个机素或机元非线性胶合而成。根据机素机元理论,中医病机是由单一的能反映整体病理状态的独立功能单元(机元)线性组成,而机元必然由机素构成。本研究提出的机素、机元理论,赋予了“瘀热”病机学说新的科学内涵,即可将瘀和热看成两个机素,它们可以衍生出相应的“热”机元、“瘀”机元,而这两个机元还能以非线性胶合形式构成新的“瘀热”复合机元,这进一步诠释了复合病机内涵。专家咨询的德尔菲法能够较快地提取中医先验经验,是获取专家先验经验的有效方法,较全面地收集了有关瘀热机元测量的表征信息,能够从重要性角度为瘀热机元测量提供可能的条目池,是形成量表初表的可行方法。专家咨询法突显了专家经验的重要性和局限性,本研究将专家经验和临床验证紧密结合,互相印证。基于机素-机元的病机辨证体系的机元证素的测量方法,本研究建立了具有较好信度和效度,具有中医特色的出血性中风瘀热机元的特异性测量量表,为机元为单元的定量测量探索了可行的路径,从而更好地传承国医大师周仲瑛教授的临证经验。
Objective:This study synthesizes various methods of differentiation of symptoms to establishs a novel TCM theory of pathogenic differentiation of symptoms based on pathogenic elements and pathogenic units according to Professor Zhou Zhong-ying's theory on pathogenesis determination.The objective is to build a standard and flexible method of differentiation of symptoms. This method can guide clinical practice better and improve quality of differentiation of symptoms. Professor Zhou Zhong-ying's theory on complex pathogenesis of stasis-heat can be explaned.To create and evaluate a scale measurement method for pathogenic unit(PU) of stasis-heat on hemorrhagic stroke.
Methods:This research applied generalized dictionary model to analyze clinical case reports from National TCM physician-Zhou Zhong-ying to establish a novel TCM theory of pathogenic differentiation of symptoms based on pathogenic elements and pathogenic units with analysis of TCM theory. Using this system illuminates connotation on complex pathogenesis of stasis-heat. Based on this system, the study on an integrative mode of Chinese medicine syndrome differentiation and disease classification for hemorrhagic stroke was done. Step one:system of measurement and items possible on indictor of statis-heat was created by means of literature study and discussion of experts. Step two:the items of measurement scale were renewed,emended and perfected by experts'expericnce with clinical symptoms. Step three:the pathogenic unit is confirmed for patients of hemorrhagic stroke, at the same time, the parameters of validity and reliability of scale were checked. This research is a part of National Emphasis Foundation Research Development Plan(973 plan)—Study of Pathogenesis and foundation of molecule for stasis-heat in refractory of internal medicine.
Results:A new system of based on pathogenic differentiation of symptoms based on pathogenic elements and pathogenic units was created by data mining. PU is an identical functional unit of pathogenesis. Clinical complicated symptoms can be regarded as linear combination of PU and indicators or items. PU of stasis-heat which is not split nonlinearly consists of PE of stasis and PE of heat. With method of experts'consultation, the dimension of scale on PU of stasis-heat for all diseases was found out, consisting of four facets of Xue-re,Xue-yu,Chu-xue and Shen-zhi. The scale includes 59 items,21 items belonging to Xue-re,15 items belonging to Xue-yu,17 items belonging to Chu-xue and 6 items belonging to Shen-zhi. The dimension of scale on PU of stasis-heat for hemorrhagic stroke was found out, consisting of three facets of Xue-re,Xue-yu, and Shen-zhi. The scale includes 32 items,19 items belonging to Xue-re,7 items belonging to Xue-yu and 6 items belonging to Shen-zhi. Cronbach's Alpha for all diseases is 0.924. Finally 25 of items were screened out, which have better reliability and significance of diagnosis based on experts' experience by clinical investigation. Multilevel structural equation mode 1 about 25 items was formed. Global goodness of fit statistics of multilevel SEM is good:Full Information ML Chi-Square=6402.47554(P<0.001),df=565, RMSEA=0.099816. This result shows model can be accepted on exterior index. Structural equation model shows association between latent variable of two order and one between. This reflects association between stasis-heat and facet (Xue-re,Xue-yu, and Shen-zhi)of scale. The result indicated Shen-zhi had more weight for stasis-heat than others, which reflects characteristic of acute hemorrhagic stroke. There are 25 manifest variables are statistical significance,which shows better fit statistics in internal assess. According to above study, the scale of PU of stasis-heat for hemorrhagic stroke were renewed and perfected. A quantitative method of measurement of stasis-heat for hemorrhagic stroke is built according to regression of factor score.
Conclusion:All kinds of methods of differentiation of symptoms of TCM have distinct rule which pathogenic analysis is core. The PE and PU flexibly and simply disclose theory of pathogenic differentiation of symptoms. PE is an independent element of pathogenesis, and PU is an independent functional unit of pathogenesis. The latter is sub-unit of pathogenesis which can be demonstrated, low-dimension and inseparable element. The PU also is definite target of drug. One PU can be transformed another PU. Measurement and standardization based on PU can embody advantage and characteristic of pathogenesis determination. Stasis-heat is complex pathogenesis unit, which may be regarded as a PU. It consists nonlinearly of PE of stasis and heat. Based on this theory complex pathogenesis of stasis and heat can be explained and clarified. The method of expert's consultation based on Delphi is feasible to form original scale, which can focus on an issue to screen important items. However this method also indicates some disadvantage because of insufficiency of experts' experience. This research applied clinical investigation data to verify experts'experience. Based on a novel theory of pathogenesis determination, a specified scale of PU of stasis and heat for hemorrhagic stroke is created, which has good validity and reliability. This study had explored feasible method to measure PU in order to clinical experience of National TCM physician-Zhou Zhong-ying.
方法：本研究以国医大师周仲瑛教授的医案为素材,采用广义字典模型(generalized dictionary model)等数据挖掘方法,结合中医医理分析构建基于机素-机元的中医病机辨证创新体系,基于该体系诠释瘀热复合病机的内涵；在此理论的指导下,以出血性中风为疾病研究切入点,开展病证结合研究,通过文献研究和专家集体讨论的方法,建立瘀热量表表征的条目池和测量的指标体系,应用专家咨询的方法,进一步补充、修订和完善测量表征；采用临床流行病学前瞻纵向调查设计和多水平结构方程模型等复杂数据的分析方法验证瘀热存在的客观性,考核出血性中风瘀热机元特异性疾病测量量表的信度和效度等参数。本研究也是国家重点基础研究发展计划(973)课题-“瘀热”病因在内科难治病发病中的机制及其分子基础研究的一部分(课题编号：2006CB504807)。
结果：通过数据挖掘方法,本研究建立了基于机素-机元的中医病机辨证体系,机元可以看成独立的病机单元或病理单元,以此为中医辨证的核心或亚单元,临床复杂的证候可以看成是机元及其相关表征的组合。瘀热机元是瘀机元和热机元的胶结合和、非线性组合,具有不可分性。通过专家咨询研究,确定了瘀热机元全病域量表的测量维度,分为血热、血瘀、出血、神志四个方面,可以通过59条目的表征信息来反应,其中血热征有21个条目,血瘀征有15个条目,出血征有17个条目,神志征有6个条目；出血性中风瘀热机元的量表分为血热、血瘀、神志三个维度,共32条目,其中血热征有19个条目,血瘀征有7个条目,神志征有6个条目,全病域测量量表专家咨询的Cronbach's Alpha信度为0.924。通过临床验证,在专家经验的基础上,结合各宏观表征的测量信度,进一步精选了瘀热表征信息,最终筛选出25个测量信度较高,专家诊断意义较大的25个表征进入多水平结构方程模型：模型拟合结果：Full Information ML Chi-Square=6402.47554 (P<0.001), df=565, RMSEA(近似误差均方根)=0.099816,表明数据模型拟合外在指数尚可,结构方程模型显示了二阶潜在变量瘀热(ξ)和一阶潜在变量(η)征象维度间的权重关系,显示了瘀热与血热(实热、虚热)、血瘀及神志变化的关系,其中神志征对瘀热贡献较大,这反应了出血性中风急性期以神志征为特征表现的疾病特点；模式内在质量考核有25个显性指标达统计学显著性；表明量表内在适配指标是可接受的。根据专家咨询和临床验证,修改和完善了出血性中风瘀热机元的测量量表,根据因子得分回归方程初步建立了瘀热机元的定量测量方法。
结论：中医多种辨证方法具有明显的规律性,病机分析是其灵魂。以机素-机元为核心的病机元素和病机单元,能更加灵活和简约地解析中医病机辨证规律；机素揭示了病机构成的基本元素,机元则是辨证的独立病理单元或亚单元,后者也是构成中医病机的低维度、不可分、可实证的病理单元和药物作用的明确靶点,机元之间可以互相演变和转化。临床上以机元为辨证亚单元的规范和测量,更能反映审证求机和审机论治的特点和优势。“瘀热”是不可拆分的复合病机单元,由瘀和热两个机素紧密构成,可以看成“瘀”和“热”两个机元非线性交互组合而成,在其致病过程中,不仅有瘀和热的共同参与,而且瘀和热之间胶结合和,有其内在的因果关联。因此瘀热实为独立的机元或病理单元,是基于“瘀”和“热”两个机素或机元非线性胶合而成。根据机素机元理论,中医病机是由单一的能反映整体病理状态的独立功能单元(机元)线性组成,而机元必然由机素构成。本研究提出的机素、机元理论,赋予了“瘀热”病机学说新的科学内涵,即可将瘀和热看成两个机素,它们可以衍生出相应的“热”机元、“瘀”机元,而这两个机元还能以非线性胶合形式构成新的“瘀热”复合机元,这进一步诠释了复合病机内涵。专家咨询的德尔菲法能够较快地提取中医先验经验,是获取专家先验经验的有效方法,较全面地收集了有关瘀热机元测量的表征信息,能够从重要性角度为瘀热机元测量提供可能的条目池,是形成量表初表的可行方法。专家咨询法突显了专家经验的重要性和局限性,本研究将专家经验和临床验证紧密结合,互相印证。基于机素-机元的病机辨证体系的机元证素的测量方法,本研究建立了具有较好信度和效度,具有中医特色的出血性中风瘀热机元的特异性测量量表,为机元为单元的定量测量探索了可行的路径,从而更好地传承国医大师周仲瑛教授的临证经验。
Objective:This study synthesizes various methods of differentiation of symptoms to establishs a novel TCM theory of pathogenic differentiation of symptoms based on pathogenic elements and pathogenic units according to Professor Zhou Zhong-ying's theory on pathogenesis determination.The objective is to build a standard and flexible method of differentiation of symptoms. This method can guide clinical practice better and improve quality of differentiation of symptoms. Professor Zhou Zhong-ying's theory on complex pathogenesis of stasis-heat can be explaned.To create and evaluate a scale measurement method for pathogenic unit(PU) of stasis-heat on hemorrhagic stroke.
Methods:This research applied generalized dictionary model to analyze clinical case reports from National TCM physician-Zhou Zhong-ying to establish a novel TCM theory of pathogenic differentiation of symptoms based on pathogenic elements and pathogenic units with analysis of TCM theory. Using this system illuminates connotation on complex pathogenesis of stasis-heat. Based on this system, the study on an integrative mode of Chinese medicine syndrome differentiation and disease classification for hemorrhagic stroke was done. Step one:system of measurement and items possible on indictor of statis-heat was created by means of literature study and discussion of experts. Step two:the items of measurement scale were renewed,emended and perfected by experts'expericnce with clinical symptoms. Step three:the pathogenic unit is confirmed for patients of hemorrhagic stroke, at the same time, the parameters of validity and reliability of scale were checked. This research is a part of National Emphasis Foundation Research Development Plan(973 plan)—Study of Pathogenesis and foundation of molecule for stasis-heat in refractory of internal medicine.
Results:A new system of based on pathogenic differentiation of symptoms based on pathogenic elements and pathogenic units was created by data mining. PU is an identical functional unit of pathogenesis. Clinical complicated symptoms can be regarded as linear combination of PU and indicators or items. PU of stasis-heat which is not split nonlinearly consists of PE of stasis and PE of heat. With method of experts'consultation, the dimension of scale on PU of stasis-heat for all diseases was found out, consisting of four facets of Xue-re,Xue-yu,Chu-xue and Shen-zhi. The scale includes 59 items,21 items belonging to Xue-re,15 items belonging to Xue-yu,17 items belonging to Chu-xue and 6 items belonging to Shen-zhi. The dimension of scale on PU of stasis-heat for hemorrhagic stroke was found out, consisting of three facets of Xue-re,Xue-yu, and Shen-zhi. The scale includes 32 items,19 items belonging to Xue-re,7 items belonging to Xue-yu and 6 items belonging to Shen-zhi. Cronbach's Alpha for all diseases is 0.924. Finally 25 of items were screened out, which have better reliability and significance of diagnosis based on experts' experience by clinical investigation. Multilevel structural equation mode 1 about 25 items was formed. Global goodness of fit statistics of multilevel SEM is good:Full Information ML Chi-Square=6402.47554(P<0.001),df=565, RMSEA=0.099816. This result shows model can be accepted on exterior index. Structural equation model shows association between latent variable of two order and one between. This reflects association between stasis-heat and facet (Xue-re,Xue-yu, and Shen-zhi)of scale. The result indicated Shen-zhi had more weight for stasis-heat than others, which reflects characteristic of acute hemorrhagic stroke. There are 25 manifest variables are statistical significance,which shows better fit statistics in internal assess. According to above study, the scale of PU of stasis-heat for hemorrhagic stroke were renewed and perfected. A quantitative method of measurement of stasis-heat for hemorrhagic stroke is built according to regression of factor score.
Conclusion:All kinds of methods of differentiation of symptoms of TCM have distinct rule which pathogenic analysis is core. The PE and PU flexibly and simply disclose theory of pathogenic differentiation of symptoms. PE is an independent element of pathogenesis, and PU is an independent functional unit of pathogenesis. The latter is sub-unit of pathogenesis which can be demonstrated, low-dimension and inseparable element. The PU also is definite target of drug. One PU can be transformed another PU. Measurement and standardization based on PU can embody advantage and characteristic of pathogenesis determination. Stasis-heat is complex pathogenesis unit, which may be regarded as a PU. It consists nonlinearly of PE of stasis and heat. Based on this theory complex pathogenesis of stasis and heat can be explained and clarified. The method of expert's consultation based on Delphi is feasible to form original scale, which can focus on an issue to screen important items. However this method also indicates some disadvantage because of insufficiency of experts' experience. This research applied clinical investigation data to verify experts'experience. Based on a novel theory of pathogenesis determination, a specified scale of PU of stasis and heat for hemorrhagic stroke is created, which has good validity and reliability. This study had explored feasible method to measure PU in order to clinical experience of National TCM physician-Zhou Zhong-ying.
引文
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13.毛炜,陈志强,王昭辉,欧爱华,925例外科手术患者围手术期证候分布规律回顾性分析.中华实用中西医杂志,2004.4(17)：p.268-269.
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15. 申春悌,朱雄华,常惠,陈启光,闵婕,更年期综合征中医辨证标准的临床研究.江苏中医药,2003.24(11)：p.12-16.
16. 申春悌,陈启光,张华强,DME的测量(M)方法在病证结合研究中的运用.北京中医药大学学报,2007.30(3)：p.160-187.
17.刘恩顺,孙增涛,封继宏,王强,1010例支气管哮喘患者中医证候及证候要素的临床流行病学调查.天津中医药,2009.26(5)：p.357-359.
18.马斌,高颖,中风病发病第7天和第14天证候要素演变规律初步研究.辽宁中医杂志,2006.33(12)：p.1561-1563.
19.刘恩顺,孙增涛,封继宏,王强,张弦,天津市支气管哮喘证候分布及演变规律的临床流行病学调查.辽宁中医药大学学报,2008.10(9)：p.126-127.
20.王雪峰,董丹,虞坚尔,吕玉霞,姜之炎,许尤佳,肖旭腾,刘小凡,儿童肺炎常见病原学分析及中医证候演变规律的多中心随机双盲安慰剂对照试验研究.中国循证儿科杂志,2006.1(3)：p.170-176.
21.陈建设,陈文垲,聚类分析结合logistic回归分析在中医证候诊断量化研究中的应用探讨.中国卫生统计,2009.26(4)：p.379-382.
22.司徒红林,林毅,欧爱华,汤凤池,刘鹏熙,陈前军,朱华宇,乳腺增生病中医证候分布规律及证候分级阈值初探.辽宁中医药杂志,2007.34(11)：p.1545-1547.
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25. 史锁芳,刘秀芳,严志林,王道成,孔祥文,沈镇苍,陈启光,闵捷,支气管哮喘患者中医四诊信息调查及验证性因子分析.中西医结合学报,2005,3(5);p.363-365.
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27. Bentler, P.M.Multivariate analysis with latent variables:Causal modeling. Annual Review of Psychology,.1980(31):p.419-456.
28. Wen Z, M.H.W., Hau K T, Interactional effects in growth modeling:A full model. Structural Equation Modeling:A Multidisciplinary Journal,2002(9):p.20-39.
29.陈启光,中春悌,张华强等,结构方程模型在中医证候规范研究中的应用.中国卫生统计,2005.22(1)：p.2-4.
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31.李国春,李春婷,黄蓝洋,单兆伟,陈启光,结构方程模型在慢性萎缩性胃炎中医证候分型中应用.中国卫生统计,2007.24(4)：p.357-361.
32.王天芳,张连文,赵燕等,隐结构模型及其在中医证候研究中的应用.北京中医药大学学报,2009.32(8)：p.519-526.
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37.赵凯维,于智敏,中医“病机”研究现状述评.中华中医药杂志,2010.25(1)：p.10-13.
38.陈亦人,《伤寒论》求是.2008,上海：上海科学技术出版社.10.
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12.李力,任婕,杜彩凤,辛意,王天芳,更年期综合征中医证候及证候要素.中华中医药杂志,2008.23(3)：p.194-197.
13.毛炜,陈志强,王昭辉,欧爱华,925例外科手术患者围手术期证候分布规律回顾性分析.中华实用中西医杂志,2004.4(17)：p.268-269.
14.陈力,肖政,急性冠脉综合征中医证候回顾研究.广州中医药大学学报,2008.25(3)：p.248-254.
15. 申春悌,朱雄华,常惠,陈启光,闵婕,更年期综合征中医辨证标准的临床研究.江苏中医药,2003.24(11)：p.12-16.
16. 申春悌,陈启光,张华强,DME的测量(M)方法在病证结合研究中的运用.北京中医药大学学报,2007.30(3)：p.160-187.
17.刘恩顺,孙增涛,封继宏,王强,1010例支气管哮喘患者中医证候及证候要素的临床流行病学调查.天津中医药,2009.26(5)：p.357-359.
18.马斌,高颖,中风病发病第7天和第14天证候要素演变规律初步研究.辽宁中医杂志,2006.33(12)：p.1561-1563.
19.刘恩顺,孙增涛,封继宏,王强,张弦,天津市支气管哮喘证候分布及演变规律的临床流行病学调查.辽宁中医药大学学报,2008.10(9)：p.126-127.
20.王雪峰,董丹,虞坚尔,吕玉霞,姜之炎,许尤佳,肖旭腾,刘小凡,儿童肺炎常见病原学分析及中医证候演变规律的多中心随机双盲安慰剂对照试验研究.中国循证儿科杂志,2006.1(3)：p.170-176.
21.陈建设,陈文垲,聚类分析结合logistic回归分析在中医证候诊断量化研究中的应用探讨.中国卫生统计,2009.26(4)：p.379-382.
22.司徒红林,林毅,欧爱华,汤凤池,刘鹏熙,陈前军,朱华宇,乳腺增生病中医证候分布规律及证候分级阈值初探.辽宁中医药杂志,2007.34(11)：p.1545-1547.
23.牟新,周旦阳,赵进喜,中医证候学研究常用统计方法学.中国中医药科技,2008.15(1)：p.56-57.
24.金香兰,张允岭,孟繁兴等,高血压病低危组证候要素初探.中华中医药杂志,2011.26(1)：p.36-39.
25. 史锁芳,刘秀芳,严志林,王道成,孔祥文,沈镇苍,陈启光,闵捷,支气管哮喘患者中医四诊信息调查及验证性因子分析.中西医结合学报,2005,3(5);p.363-365.
26.侯杰泰,温忠麟等,结构方程模型及其应用.2005,北京：教育科学出版社.13.
27. Bentler, P.M.Multivariate analysis with latent variables:Causal modeling. Annual Review of Psychology,.1980(31):p.419-456.
28. Wen Z, M.H.W., Hau K T, Interactional effects in growth modeling:A full model. Structural Equation Modeling:A Multidisciplinary Journal,2002(9):p.20-39.
29.陈启光,中春悌,张华强等,结构方程模型在中医证候规范研究中的应用.中国卫生统计,2005.22(1)：p.2-4.
30.李国春,陈文垲等,中医宏观辨证指标量化方法研究探讨.中国中医基础医学杂志,2005.22(1)：p.2-3.
31.李国春,李春婷,黄蓝洋,单兆伟,陈启光,结构方程模型在慢性萎缩性胃炎中医证候分型中应用.中国卫生统计,2007.24(4)：p.357-361.
32.王天芳,张连文,赵燕等,隐结构模型及其在中医证候研究中的应用.北京中医药大学学报,2009.32(8)：p.519-526.
33.中国中医研究院,岳美中论医集.1980,北京：人民卫生出版社.561.
34.孙霈,有关“症”、“征”、“证”医学用法的研讨和约定,in科技术语研究.2003.p.21-22.
35.汉·许慎撰,清.段.,说文解字注.1981,上海：上海古籍出版社.56.
36.刘保延,王永炎,证候、证、症的概念及其关系的研究.中医杂志,2007.48(4)：p.293-298.
37.赵凯维,于智敏,中医“病机”研究现状述评.中华中医药杂志,2010.25(1)：p.10-13.
38.陈亦人,《伤寒论》求是.2008,上海：上海科学技术出版社.10.
39.李国春,吴勉华,周学平等,基于机素和机元中医病机创新理论的辨证规律研究.南京中医药大学学报,2010.26(2).
40.卢红蓉,潘桂娟,中医病机特点与辨识方法探讨.中医杂志,2010.51(12)：p.1064-1067.
41.赵凯维,中医病机概念诠释,in中医基础理论研究所.2010,中国中医科学院：北京.p.20-25.
42.孟庆云,从病机的语义特征剖析其内涵.上海中医药大学学报,1999.13(2)：p.7.
43.李国春,吴勉华,周学平,叶放,金妙文,邓柯,基于机素和和机元中医病机创新理论的辨证规律研究.南京中医药大学学报,2010.26(2)：p.81-84.
44.李国春,吴勉华,周学平,叶放,论中医证的结构.中华中医药杂志,2010.25(1)：p.81-84.
45.方药中,辨证论治研究七讲.1979,北京：人民卫生出版社.96.
46.爱因斯坦(许良英、范岱年译),《爱因斯坦文集》第一卷.1976,北京：商务印书馆.