| Objective:1.Systematically evaluate the effectiveness and safety of acupoint application therapy in the treatment of primary dysmenorrhea,and use data mining technology to explore the medication and acupoint selection rules of acupoint application therapy for this disease.2.Evaluate the clinical effect of graphene Nuangong acupoint plaster in the treatment of primary dysmenorrhea by observing the clinical symptoms,emotional state,quality of life and changes in energy metabolism in acupoint area of patients with dysmenorrhea before and after treatment.3.Non-targeted metabolomics was used to screen the differential metabolites and key signaling pathways in the uterine tissue of PD model rats to reveal the biological effect mechanism of graphene Nuangong acupoint plaster in the treatment of PD.Methods:1.Literature researchAccording to the search strategy,the Chinese and English databases were searched,and the randomized controlled trials and eligible clinical trials of Acupoint Application in the treatment of PD were included.The Cochrane manual was used to evaluate the quality of the included RCT studies,and Revman 5.3 software was used for meta-analysis.Meanwhile,Microsoft Excel 2016,SPSS statistics 25.0 and SPSS modeler 18.0 were used to conduct descriptive analysis,cluster analysis and association rule analysis of the included clinical studies.2.Clinical research60 patients with primary dysmenorrhea were randomly divided into graphene Nuangong acupoint sticking group and Yuanhu Zhitong tablet group with 30 cases in each group.Cox dysmenorrhea symptom scale was used as the main outcome observation index,and visual analogue scale of pain,simplified Mc Gill pain score,Beck Anxiety Scale,Beck Depression Scale,health survey brief table,the intervention credibility survey and the results of biological ultra-weak luminescence detection and infrared thermal imaging detection were used as secondary outcome indicators.The improvement before and after treatment and the evaluation period of each course were observed,and the efficacy of the two kinds of intervention treatment was evaluated.3.Experimental studyThe primary dysmenorrhea rat model was established by subcutaneous injection of estradiol benzoate combined with oxytocin.After the intervention treatment,the writhing reaction of rats was observed and the uterine tissues of rats in each group were collected for sample processing.The ultra performance liquid chromatography high resolution mass spectrometry method was used to screen the differential metabolites of uterine samples of rats in each group through multidimensional statistical analysis,and the biological information of the differential metabolites was analyzed,the KEGG pathway of significantly different metabolites was obtained.Results:1.Literature research resultsThe results of meta-analysis showed that:(1)acupoint application combined with traditional Chinese medicine in the treatment of primary dysmenorrhea was superior to traditional Chinese medicine in terms of effective rate,reducing VAS score and improving dysmenorrhea symptoms;(2)Simple application in the treatment of PD is superior to western medicine in terms of effective rate,improvement of pain symptoms,and long-term efficacy;(3)Compared with the traditional Chinese medicine group,the application has advantages in effective rate and improving clinical symptoms;(4)In terms of adverse reactions,there was no significant statistical difference between the application group and traditional Chinese medicine and Western medicine.Based on data mining technology,a total of 70 literatures were included in this study,including 81 drugs and 24 acupoints.According to the frequency statistics,the top five drugs used frequently are Rhizoma Corydalis,cinnamon,asarum,Angelica sinensis and Ligusticum chuanxiong.Most of the drugs are pungent,sweet and bitter,and the properties are warm and hot.The top 5 acupoints used frequently are Guanyuan,Shenque,Zhongji,Sanyinjiao and uterus,and renmai acupoints are the main ones.Cluster analysis found that high-frequency drugs and acupoints could be clustered into five categories.Association rules showed that 16 association rules were obtained for high-frequency drugs;29 association rules were obtained from acupoint selection.2.Clinical research resultsAfter three menstrual periods of clinical treatment,the comparison between the two groups before and after treatment found that the patients’ CMSs dysmenorrhea symptom score,VAS score,SF-MPQ score decreased significantly and there were differences in the scores at each time point,indicating that the efficacy of the two intervention treatments was stable and sustained.The effect size test between groups found that the group had no significant effect on the CMSs score,VAS score and SF-MPQ score,and there was no main effect,indicating that the two groups had the same overall effect in improving the symptoms of dysmenorrhea pain,reducing the degree and time of pain,but the score of graphene Nuangong acupoint plaster group was slightly lower than that of Yuanhu group.In terms of Bai,BDI-II and SF-36 scores,the anxiety,depression and quality of life scores of the two groups were significantly improved,but the graphene acupoint sticking group had certain advantages in improving anxiety and mental health compared with the Yuanhu group.PMT was used to detect the number of self luminous photons in the acupoint area.It was found that the number of photons in the local Guanyuan and uterine acupoint areas in the two groups was significantly increased before and after treatment;After treatment,the photon number of Guanyuan and uterus acupoints in Yuanhu group was significantly higher than that of acupoint sticking group,but there was no significant change in the photon number of distal Sanyinjiao acupoint before and after treatment;The number of photons in Sanyinjiao acupoint area in acupoint sticking group increased significantly after treatment.In terms of infrared imaging detection of acupoint infrared temperature,the infrared temperature of Guanyuan acupoint in Yuanhu group increased significantly after treatment;After treatment,the infrared temperature of Guanyuan and Sanyinjiao points increased significantly in the acupoint sticking group;However,there was no significant difference in the infrared temperature between the acupoints in the two groups,and both had the trend of increasing the infrared temperature in the acupoint area.In the investigation of intervention credibility before and after treatment,it was found that patients in the graphene acupoint sticking group had more confidence in the treatment they received.In terms of clinical total effective rate,the total effective rate of Yuanhu group was 79.31%,and that of graphene acupoint sticking group was 82.75%.There was no significant difference between the two groups.3.Experimental research resultsBefore and after modeling,the weight of rats in the four groups changed significantly,the weight of rats in the normal blank group increased significantly,and the weight of rats in the model group,acupoint sticking group and Yuanhu group decreased significantly.The observation of writhing reaction showed that compared with the blank group,the latency time of the model group was significantly reduced,and the number of writhing was significantly increased;Compared with the model group,the latent time of Yuanhu group and acupoint sticking group was significantly longer,and the number of writhing was significantly reduced.Compared with the normal blank group,the weight of uterus in the model group,Yuanhu group and graphene acupoint sticking group increased significantly;Compared with the model group,the uterine mass of rats in Yuanhu group and graphene acupoint sticking group decreased significantly.According to the analysis of non targeted metabolomics technology,79 different metabolites were screened out from the uterine samples of the model group compared with the blank group,mainly lipids and lipid molecules,organic acids and their derivatives,organic oxygen compounds,etc.There are 23 enriched pathways,including arachidonic acid metabolism,primary bile acid anabolism,ovarian steroid metabolism and AMPK signaling pathway,which are mainly involved in carbohydrate,amino acid,nucleotide and cofactor,vitamin,lipid metabolism,etc.After the treatment of graphene Nuangong acupoint sticking and Yuanhu Zhitong tablets,a variety of differential metabolites related to PD occurred callback,and the differential metabolites of the two groups were jointly enriched into the vitamin B6 metabolic pathway compared with the model group.Conclusion:1.According to systematic review and meta-analysis,acupoint application therapy has reliable curative effect in the treatment of primary dysmenorrhea,and has certain advantages in improving clinical symptoms,long-term efficacy and safety.2.Through data mining,the clinical medication and acupoint selection of Acupoint Application in the treatment of PD were summarized,and the medication and acupoint selection rules of acupoint application were in line with the etiology and pathogenesis of the disease.The core medication and acupoint selection rules provided a reference for clinical treatment.3.Graphene Nuangong acupoint sticking and Yuanhu Zhitong tablets can effectively treat primary dysmenorrhea,mainly in reducing patients’ pain response,improving clinical symptoms,improving patients’ psychological and physical health,and strengthening energy metabolism in acupoint areas.There was no significant difference in the clinical total effective rate between graphene Nuangong acupoint sticking and Yuanhu Zhitong tablets,but it was better than drug treatment in improving bad mood and patient acceptance and satisfaction.4.From the perspective of metabolomics,it was found that metabolic pathways and related metabolites such as arachidonic acid metabolism,primary bile acid biosynthesis,and ovarian steroidogenesis were altered in PD model rats.Graphene Nuangong acupoint sticking and Yuanhu Zhitong tablets may regulate vitamin B6 metabolism and other pathways and callback a variety of potential PD metabolites to exert clinical effects,but further research is still needed to verify the results. |
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