| Syndrome has the characteristics of "internal stability and external flexibility". The "internal stability" means the key syndrome that reflects pathogenesis and the common character in the group, which is the basis of intervention. The "external flexibility" means the individual syndrome, which can affects the principle and method of intervention. Therefore, if the syndrome target is different, the significance to evaluate efficacy is different. Nimodipine is the common method to evaluate the syndrome efficacy, which doesn’t conform to the characteristics of "internal stability and external flexibility". So the study proposed that deconstruction to syndrome and analysis to "internal stability" dynamic changes is the key part to evaluate syndrome efficacy.Syndrome is the dynamic process which varies with time, and so are the"internal stability" and "external flexibility" parts of Syndrome. The recognization of the dynamic change trend of syndrome especially "internal stability" and "external flexibility" part of Syndrome is the important foundation for the application into the clinical practice and enhancement of the treatment effect of TCM, and the critical process to evaluate the efficacy of the syndrome. Based on the theory of "internal stability and external flexibility" proposed by Pro. Wang Yongyan, a randomized, double-blind, multi-center trial of Xinxuekang Capsule for blood stasis syndrome of angina pectoris of coronary heart disease was conducted to find an approach to evaluating the effect in TCM syndrome.Object:To discuss the effect of the drug for Syndrome and the "internal stability" part of Syndrome under the change of time by clinical annotation to "internal stability and external flexibility" of Syndrome and its dynamic change, which would provide new method to evaluate the efficacy of the syndrome.Method:Based on the randomized, blind, multi-center clinical trial data of Xinxuekang capsule for the treatment of blood stasis syndrome in angina pectoris of coronary heart disease (CHD-AP-BSS),the study determined the latent class and the"internal stability" part of CHD-AP-BSS according to the latent class modeling (LCM). According to the class of the data, the study analyzed the change of latent class and single symptom of CHD-AP-BSS by Generalized Estimating Equations (GEE).And then the study discussed the dynamic change trends of syndrome and "internal stability" part of syndrome by similarity analysis under the different interventions based on the dynamic changes of dimensional data such as syndrome and "internal stability" part of syndrome. At last, the study applied NONMEM into the analysis of the changes in similarities with time.Results:1. According to the comparisons of the baseline in A and B2 groups, there were not any significant differences in CHD-AP, BSS and other test results between the two groups.2. By t-test analysis, the study found that the changes of the syndrome score between 4w,6w,8w or 3m after treating and baseline were significant, respectively. The changes of the syndrome score between A and B group at the 3 m after treating were significant, respectively.By single factor analysis of variance of repetitive measurement, the study found that syndrome score decreased by time. The changes of the syndrome score between 2w,4w,6w,8w or 3m after treating and baseline were significant, respectively. The changes of the syndrome score between A and B group at the 4w,6w,8w or 3m after treating were significant, respectively.The results of t-test analysis and single factor analysis of variance of repetitive measurement is different. The latter is the common method to analyze the repetitive measurement data, which the results is dependable.3. Based on the results of LCM to CHD-AP-BSS, the study found that the patients can be classified to "the mild" and "the serious". The symptoms like chest pain, chest distress, dark purple lip, dark tongue were relatively more stable than other symptoms in CHD-AP-BSS, which is the "internal stability" part of CHD-AP-BSS.4. Based on the results of similarity analyses to CHD-AP-BSS at different times and in different groups by Cosine method, Dice method and Jaccard method, the study found that the total change trend of the similarity values was similar by different methods, although the details of similarity values were different in different methods, which shows that the similarity values were decreased gradually in both A and B groups with the time of treatment. It suggested that both A and B group can improve the blood stasis syndrome.Analyzing syndrome changing trend with time by nonlinear mixed effected model, the research found that similarity of syndrome changed with time in both A and B groups. The change of the similarity was influenced by angina pectoris scores, "internal stability" part of syndrome, et al. At the same time, the factor "group" was related to the change of syndrome, which suggested that the change of syndrome between A group and B group was different significantly.Take the similarity values equal to 0.8 as the boundary point, the study found that at that time, A is used 7.28w and B is used 10.72w, which is considered to the change of CHD-AP-BSS.5. By LCM and GEE, the research found that the latent class in 2w,4w,6w,8w and 3m was significantly different compared with the baseline, respectively. At the 4w, the factor "time" and "group" existed interaction. The results illustrated that CHD-AP-BSS alleviates gradually. The change of latent class in 4w after treatment between A group and B group is different significantly.6. Based on the results of the similarity values of "internal stability" part of CHD-AP-BSS at different time and in different groups by Cosine method, Dice method and Jaccard method, the research found that although the similarity values were different by different methods, its total change trend was similar in each method. It suggested that the similarity values were decreased gradually in both A and B groups with the time of treatment, which illustrated that both A and B group can improve the "internal stability" part of CHD-AP-BSS.According to the analysis of the correlation between the change of "internal stability" part of CHD-AP-BSS and time by NONMEM, the results showed that similarity of "internal stability" part of syndrome changed with time. The factor "test centre" was an influence factor for the similarity change of "internal stability" part in both A and B group. The factor "angina pectoris scores" affected the similarity change of "internal stability" part of CHD-AP-BSS only in B group. The difference of similarity change of "internal stability" part of CHD-AP-BSS between group A and group B was significant.7. According to the analysis of the single symptoms of CHD-AP-BSS by rank test, the study found that the changes of symptom scores of chest pain, chest distress, palpitation, dark purple lip, tongue and pulse manifestations in 2w,4w,6w,8w and 3m were significantly different significantly compared with the baseline except pulse manifestations in 2w,4w in B group. The differences of chest pain in 20w, palpitation in 2w,4w,8w and 20w, tongue picture from 4w to 20w between group A and group B were significant.According to the analysis of the single symptoms of CHD-AP-BSS by GEE, the research found that the changes of symptom scores of chest pain, chest distress, palpitation, dark purple lip, tongue and pulse manifestations in 2w,4w,6w,8w and 3m were significantly different significantly compared with the baseline, and the differences between the symptoms scores at the two adjacent time points were also different significantly. It indicated that both drug A and B could improve the symptoms of CHD-AP-BSS and the longer the patients were treated, the better the efficacy would be got. The differences of chest pain in 20w, palpitation from 2w to 20w, tongue picture from 4w to 20w between group A and group B were significant.The results of rank test analysis and single factor analysis of variance of repetitive measurement is different. The latter is the common method to analyze the repetitive measurement data, which the results is dependable. Conclusion1. Symptoms contributing to the syndrome, the latent class and the "internal stability" part of the syndrome and the syndrome itself are in constant change with space and time. The effect in TCM syndrome can be evaluated by analyzing the change of contributing symptoms, the "internal stability" part of the syndrome and the syndrome itself。2. LCM can analyze the contribution of symptom to syndrome, which can find out the "internal stability" part of the syndrome. LCM is one of the effective methods to annotate, the "internal stability" part of the syndrome.3. The data type should be considered carefully during analysis. When the data belongs to repeated measurement data, the relationship between data in different observation point must be considered. The analysis method should be fit for repeated measurement data.4. The integration method of similarity analysis and NONMEM can better display the high dimensionality and nonlinear character of syndrome and find out the inflection point of syndrome change.5. The study suggested that syndrome has the character of constitutive property and criticality, which provides part theoretical foundation and technical support for efficacy evaluation of treatment based on syndrome differentiation.The study proposed that the analysis to the dynamic change of "internal stability and external flexibility" of syndrome was the entry point to evaluate the effect in TCM syndrome for the first time. Determine the "internal stability and external flexibility" of syndrome by LCM. Determine the dynamic change trend and the knee point of the change in syndrome by similarity analysis and NONMEM. The approach of analysis to dynamic change trend by similarity analysis and NONMEM is suitable for syndrome study, which is one of the entry points to evaluate the effect in TCM syndrome. But due to the complicated property of the syndrome, the further study is needed in the future.2. The study suggested that the change of "internal stability" part of syndrome was the main indicator to evaluate the effect in TCM syndrome. However, the relationship between the change in "external flexibility" part of syndrome and the effect of syndrome isn’t discussed in this study, which is the direction to further study. |
PDF Full Text Request