| This dissertation consists of two related parts, part one is the analysis of formula application for metrorrhagia in the ancient literature. The second part is about the clinical study of tinvigorating spleen and replenishing Qi in treating metrorrhagia of spleen Qi deficiency. A. Bibliometric analysis component Objective:This research systematicly retrieved medical records about metrorrhagia in the Chinese ancient literature through the "Encyclopaedia Of Traditional Chinese Medicine". With the aid of Traditional Chinese Medicine Inheritance Support System, which is found by Yang Hongjun in Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, for data mining, this studies analyzed and summarized medication experience and composition rules of metrorrhagia in ancient literature, just to provide certain theoretical basis of clinical treatment and scientific research for metrorrhagia. Methods:Alternatively ancient retrieval words were obtained by retrieving modern gynecology works, then the retrieval words were established by expert opinion survey method. Medical records about metrorrhagia were systematicly retrieved from "Encyclopaedia of Traditional Chinese Medicine". Then the related medical records were elaborately selected based on the inclusion criteria and exclusion criteria. The medical prescription information was put into the Traditional Chinese Medicine Inheritance Support System. The prescription medication experience and composition rules about metrorrhagia were analyzed and data mining through the help of association rules analysis, improved mutual information method, complex system entropy clustering and unsupervised entropy hierarchical clustering, which are all contained in the analysis function of the platform. Meanwhile, new prescriptions were explored on the basis of the foregoing.Results:1. ccording to the statistical results table of expert consultation, the recommended rate of more than 50% of the search words are as follows血崩、漏下、崩漏、暴崩、经漏、崩血、崩中.Being screened,214 medical records ofmetrorrhagia are ultimately incuded, with a total of 287 prescriptions, and involving 305 kinds of Chinese herbal medicine. The database of metrorrhagia medical treatment is set up, application frequency of herbs and channel tropism of all herbs are counted.2.32 high frequency-used herbs, with use frequencies above 20 or more, account for 61.64 percent of all herbs frequency. Most herbs used are owned by the spleen, liver, lung, heart, kidney. Medical prescription of the ancient records about metrorrhagia, herbs most commonly are used for invigorating spleen and replenishing Qi, and nourishing the blood and hemoslasis, mostly sijunzi decoction and siwu decoction, secondly for removing pathogenic heat from blood and promoting blood circulation to remove blood, that verify the pathogenesis characteristics of metrorrhagia:deficiency, heat and blood stasis.3.29 commonly used herbal combinations are assessed, involving nine kinds of Chinese herbs, and consistent with the high frequency of herbs. The top five pharmaceutical compositions respectively are flavored licorice and white, peony root and angelica, licorice and angelica, Atractylodes and angelica, Atractylodes and Astragalus. After setting the correlation degree and the punishment degree, the core combination of 3-5 herbs are obtained, which is 32. The core combination is extracted firstly, then by the unsupervised hierarchical clustering algorithm,15 new cluster of potential combinations are obtained. Conclusion:Medical prescription of the ancient records about metrorrhagia, herbs most commonly are used for invigorating spleen and replenishing Qi, and nourishing the blood and hemoslasis, secondly for removing pathogenic heat from blood and promoting blood circulation to remove blood, that corresponding to the pathogenesis characteristics of metrorrhagia:deficiency, heat and blood stasis. Traditional Chinese Medicine Inheritance Support System can be convienently used for data administration and statistical analysis. Data mining of the Traditional Chinese Medicine Inheritance Support System can objectively, and multi-angledly analysis and excavate prescriptions. With the help of this software, we can do the data mining of the herbal administration experience and composition principle of metrorrhagia in ancient literature from "Encyclopaedia Of Traditional Chinese Medicine", to provide a basic clinical theory, literature basis and evidence of evidence-based medicine for treatment of the anovulatory abnormal uterine bleeding. New prescriptions which are excavated from the study may provide useful clues for basic research or clinical practice. We can further prove their efficacy and mechanism of action in clinical practice and experimental research.B. Clinical research componentObjective:Being based on medical academic thought inheritance, and combining with previous literature research foundation, this study took professor Li Liyun’s experience in treating metrorrhagia as the starting point, to verify the efficacy and safety of invigorating spleen and replenishing Qi in treating metrorrhagia by prospective controlled clinical study. This study will provide evidence based medicine for the treatment of this disease, also provide a demonstration for the same kind of research.Methods:The prospective controlled trial is used in this study. Patients meeting the standard of diagnostic criteria and inclusion criteria were included in the Department of Gynecology of Guangdong Province Traditional Chinese Medical Hospital during March 2015 to March 2016.66 eligible subjects were divided into two groups:treatment group and control group. The treatment group was treated with Chinese medicine of invigorating spleen and replenishing Qi, while the control group received Dydrogesterone Tablets for half cycle therapy. The treatment period was 3 menstrual cycles, the observation time was before treatment and the next menstrual cycle after the end of treatment, the curative effect and safety index were observed. Take observation of the recovery of menstrual cycle, menstrual period, menstrual volume and basic body temperature of all patients. Monitor routine blood test, sex hormone and T lymphocyte subsets, hemorheology, also fill in the TCM Syndrome Scale. Then monitor the safety indicators, as urine and stool routine, liver and kidney function, blood coagulation function, and record adverse drug reactions to evaluate the clinical efficacy and safety of invigorating spleen and replenishing Qi in treatment of patients with ovulatory abnormal uterine bleeding. Establish the database and analysis the data by SPSS17.0 software package.Results:1. Before treatment, all index, as the age, gravidity, parity, menstrual disorder, vaginal hemorrhage time, TCM syndrome score, and hemoglobin, the level of sex hormones, T lymphocyte subsets, hemorheology between the treatment group and the control group, has no no statistical significance (P>0.05). The baseline between two groups is in equilibrium.2. Comparison of TCM syndromes before and after treatment:Comparison of the TCM syndrome between the two groups after treatment, the difference was statistically significant (P<0.05), and TCM syndrome of the treatment group is more effective than the control group. Further comparison of the TCM symptom score:Compared between the two groups, the total score of TCM syndrome and secondary symptoms scores in the treatment group is lower than the control group, and the difference is statistically significant (P<0.05, or P<0.01). Compared within group, after treatment, the total score of TCM syndrome, the main symptoms and secondary symptoms scores in both the treatment group and the control group are lower than before treatment, and the difference is statistically significant (P<0.01). Compared the difference of TCM syndrome score between the two groups before and after treatment, the treatment group has better effect than the control group decreasing in the total score of TCM syndrome, and secondary symptoms scores, the difference is statistically significant (P<0.05). It indicates that Chinese medicine has better curative effect than that of Western medicine Progesterone Tablets in improving the symptoms related with spleen deficiency, such as pale complexion, fatigued spirit and lack of strength, poor appetite, loose stools, and et al.3. Comparison of the curative effect of regulating menstruation before and after treatment:Comparison of the menstrual cycle between the two groups after treatment, and menstrual cycle of the treatment group is less than the control group, the difference was statistically significant, (P<0.05). Compared within group, after treatment, the menstrual cycle of both two groups is less than before treatment, and the difference is statistically significant (P<.0.01). Compared the difference between the two groups of the menstrual cycle before and after treatment, the difference in the treatment group is greater than the control group, and the difference is statistically significant (P<0.05). Results of Wilcoxon rank sum test of two independent samples show that there is not statistically significant difference in the curative effect of regulating menstruation between the treatment group and control group (P>0.05). Basis body temperature recovery is compared between groups, without statistically significant difference (P>0.05). Invigorating spleen and replenishing Qi has equal effect of regulating menstruation with Dydrogesterone Tablets.4. Comparison of hemoglobin before and after treatment:Compared between the two groups, hemoglobin the treatment group is higher than the control group, and the difference is statistically significant (P<0.05). Compared within group, after treatment, hemoglobin in both the treatment group and the control group is higher than before treatment, and the difference is statistically significant (P<0.01). Compared the difference between the two groups of hemoglobin before and after treatment, the treatment group has better effect than the control group, and the difference is statistically significant (P<0.05). For the treatment of anemia, the results of the χ2 test showed that the treatment group has better effect than the control group, the difference is statistically significant (P<0.05). Chinese medicine of invigorating spleen and replenishing Qi has better effect in curing anemia and increased hemoglobin values than the control group.5. Comparison of sex hormones before and after treatment:Compared between the two groups, there is not statistically significant in FSH, PRG, E2 and PRL value between the treatment group and the control group after treatment (P>0.05). But after treatment, T, LH in the treatment group is lower than the control group, and the difference is statistically significant (P<0.05 or P<0.01). Compared within group, after treatment, LH in the treatment group is lower than before treatment, and the difference is statistically significant (P<0.05 or P<0.01). While LH in the control group is higer than before, and the difference is not statistically significant (P>0.05). After treatment, PRL in the treatment group is higher than before, and the difference is statistically significant (P<0.05). RPL in the control group is higer than before, too, but the difference is not statistically significant (P>0.05). After treatment, E2 in both the treatment group and the control group are lower than before, and the difference is statistically significant (P<0.05). This result is stable in the two groups. Compared the difference between the two groups of sex hormones before and after treatment, the difference is not statistically significant (P>0.05). Chinese medicine of invigorating spleen and replenishing Qi and Western medicine both can reduce the E2 level, resist estrogen stimulation of the endometrium, and promote the endometrial change into secretion phase, to treat anovulatory abnormal uterine bleeding.6. Comparison of T lymphocyte subsets before and after treatment:Compared between the two groups, there is not statistically significant in CD3+ T cell, CD4+ T cell, CD8+ T cell, and CD4+/CD8+ between the treatment group and the control group after treatment (P> 0.05). Compared within group, after treatment, CD3+ T cell, CD4+ T celll, and CD4+/CD8+ in both two groups is higer than before treatment, and the difference is statistically significant (P <0.05 or P<0.01). Compared the difference between the two groups of T lymphocyte subsets before and after treatment, the difference of CD4+/CD8+ in the treatment group is greater than the contron group, and the difference is statistically significant (P<0.05). While there is not tatistically significant in other index (P>0.05). The increase of CD4+/CD8+ in the treatment group is better than that of the control group. Chinese medicine of invigorating spleen and replenishing Qi can improve the state of spleen deficiency and the low immunity state of patients with anovulatory abnormal uterine bleeding.7. Comparison of hemorheology before and after treatment:Compared between the two groups, there is not statistically significant in all indexes of hemorheology between the treatment group and the control group after treatment (P>0.05). Compared within group, after treatment, the whole blood viscosity under different shear rate, plasma viscosity, hematocrit, red blood cell aggregation index in both two groups is lower than before treatment, and the difference is statistically significant (P<0.05 or P<0.01). Compared the difference between the two groups of hemorheology before and after treatment, there is not statistically significant all indexes (P>0.05). The descrease of hemorheology in the treatment group suggests Chinese medicine of invigorating spleen and replenishing Qi can improve hemorheology.Conclusion:Chinese medicine of invigorating spleen and replenishing Qi can effectively improve menstrual disorders of the patients with anovulatory abnormal uterine bleeding, including hemostasis, adjusting the menstrual cycle, reducing bleeding duration and bleeding amount, which has a considerable effect with the western medicine Dydrogesterone Tablets. It can reduce the E2 level in the follicular phase, resist estrogen stimulation of the endometrium, promote the endometrial change into secretion phase, improve the state of spleen deficiency and the low immunity state of patients, and regulte hemorheology, decrease the whole blood viscosity under different shear rate, plasma viscosity, hematocrit, red blood cell aggregation index. In the two groups before and after treatment, their safety index is not abnormal, and there is not any obvious adverse drug reaction happened in the two groups. This study shows that Chinese medicine of invigorating spleen and replenishing Qi has a good clinical efficacy and safety in treating anovulatory abnormal uterine bleeding, and it is worth of clinical popularization and application. |
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