Meta-analysis And The Study Of The Rule Of Syndrome Differentiation Of Acupuncture Treatment For Perimenopausal Syndrome In The Past 30 Years

ObjectiveThe application and study of traditional Chinese Medicine increased in recent decades.The study related to the Perimenopause syndrome increased steadily too.By collecting and analysing the studies related to the use of acupuncture in treating PMS in recent 30 years,our study using the method of evidence based medicine to conduct systematic review and Meta analysis.Moreover,using data mining method to analyse the rule of syndrome differentiation of acupuncture treatment for PMS,so that more evidence can prove the use of acupuncture in clinical sector and for more future studies.MethodsElectronically and manual search databases in China’s mainland(include Hong Kong,Macao and Taiwan regions)and oversea regions to collect randomized controlled trials(RCTs)studies related to the acupuncture treatment for perimenopausal syndrome from January 1,1990 to December 31,2019.Screen and extract data according to the inclusion and exclusion criteria.Import data into spreadsheets for analysis: ?Data mining method: perform statistical description and analysis of various data through statistical analysis software.In order to describe the distribution of syndromes and symptoms,meridian distribution and acupoint characteristics.Analysis of statistical results by using traditional Chinese medicine theory and acupuncture theory.?System review and Meta analysis: According to the modified Jadad score,the quality of the included RCTs will be evaluated,and high-quality(score ≥ 4 points)research data will be extracted for further bias risk analysis and metaanalysis.Heterogeneity analysis,sensitivity analysis,subgroup analysis based on different items of concern,and publication bias analysis will be conducted for further discussion.Results1.Data collection: Relevant keywords were used to search and collect data in China’s mainland(include Hong Kong,Macao and Taiwan regions)and oversea region databases.A total of 1,124 studies were initially retrieved.534 duplicate studies were excluded through Note Express.According to the inclusion and exclusion criteria,450 non-conforming studies were excluded.A total of 140 studies were included.98 studies were further excluded according to the modified Jadad score.42 high-quality studies(score 4-7points)were included for further systematic review and Meta analysis.A total of 3886 participants were involved,including 1902 in the acupuncture treatment group and 1984 in the control group.2.Systematic review and Meta analysis: 42 high-quality studies(Jadad score 4-7 points)were included for further systematic review and Meta analysis.2.1.Total effective rate:The acupuncture group is superior to the control group in improving the total effective rate,the difference is statistically significant(P<0.01).The differences between acupuncture group and control subgroups(western medicine control group,herb control group and placebo acupuncture control group)are statistically significant(P <0.01).2.2.PMS related symptoms: The acupuncture group is better than the control group in improving Kupperman(KI)score,the difference is statistically significant(P <0.01).There is no statistically significant difference between the acupuncture group and the control group in menopauserating scale(MRS)(P>0.05).The acupuncture group is superior to the control group in improving the TCM symptom score,the difference is statistically significant(P <0.05).Subgroup analysis shows that when the course of treatment is ≤4w,the difference is statistically significant(P <0.01).2.3.Quality of life: There is no statistically significant difference between the acupuncture group and the control group in the menopausespecific quality of life questionnaire(MENQOL)(P>0.05).2.4.Serum sex hormone level: There is no significant difference in serum E2 value,FSH value and LH value between the acupuncture group and the control group(P> 0.05).2.5.Depression Scale: The acupuncture group is superior to the control group in improving the Hamilton Depression Scale(HAMD),the difference is statistically significant(P <0.01).Subgroup analysis shows that when the course of treatment is> 6w,the difference is statistically significant(P<0.01).2.6.Sleep Quality: The acupuncture group is better than the control group in improving the Pittsburgh Sleep Quality Index(PSQI),the difference is statistically significant(P <0.01).2.7.Hot flush score: There is no statistically significant difference between the acupuncture group and the control group in the hot flush score(P> 0.05).3.Risk of bias analysis: The overall risk sorting from the lowest are the generation of random sequence(selection bias),incomplete outcome data(attriton bias),selective reporting(reporting bias),other bias,allocation concealment(selection bias),blinding of outcome assessment(detection bias),blinding of participants and personnel(performance bias).3.1.Sensitivity analysis: It shows that the choice of analysis model,data set and other factors have low sensitivity.The stability of overall results is good,proving that the credibility of evidence is good.3.2.Funnel plots analysis: Analysis is conducted for the total effective rate,KI score,serum E value,serum FSH value,serum LH value,and incidence of adverse events,and the results show that there is possibility of publication bias for the total effective rate and serum FSH value.4.Frequency analysis results: 140 literature are included for frequency analysis.The total frequency of acupoints is 1193,involving 98 acupoints.4.1.Acupoints frequency:The total frequency of acupoints ranking from the highest order are Sanyinjiao,Taichong,Shenshu,Shenmen,Zusanli,Baihui,Guanyuan,Ganshu,Taixi.The frequency of acupoints according to the mode of treatment.The most frequently used acupoints for diseases identification are Sanyinjiao,Guanyuan,Shenshu,Baihui,Shenmen,Zusanli,Neiguan,Ganshu,Tianshu,and Zigong.The most frequently used acupoints for syndrome differentiation are Taixi,Shenmen,Sanyinjiao,Taichong,Shenshu,and Baihui.The most frequently used acupoints for symptom differentiation are Sanyinjiao,Taichong,Shenmen,Shenshu,Zusanli,and Baihui.4.2.Meridians frequency:The acupuncture treatment of PMS involves the twelve meridians,governor vessel and conception vessel.The most frequently used meridians are bladder meridian,spleen meridian,conception vessel,governor vessel,stomach meridian.4.3.Acupoint location frequency: The order from highest are lower limbs,back-lumbar,head-face-neck,upper limbs and chest-abdomen.4.4.Specific points frequency: The acupuncture treatment for PMS involves 71 specific points(72%),and 27 non-specific points(28%).The most frequently used types of specific points are crossing points,five transport points,source point,transport point and alarm point.The most frequently used specific points are Sanyinjiao,Taichong,Shenmen,Shenshu,Guanyuan,Zusanli,Baihui,Ganshu,and Taixi.5.Association rule analysis: Association rule analysis applied the Apriori algorithm with support level >10%,confidence level >80%,and lift value>1.5.1.Acupoints combination: A total of 20 association rules are obtained,in which the maximum confidence are ZigongàGuanyuan(94.44%),ZigongàSanyinjiao(94.44%),YintangàBaihui(94.44%).5.2.Acupoints location combination: A total of 12 association rules are obtained,in which the maximum confidence are head-face-neckàlower limb(96.94%),lumbar-backàlower limb(96.77%),abdomenàlumbar-back(96.08%).5.3.Specific points combination: A total of 21 association rules are obtained for the type of specific points combinantiao,in which 5 groups reached 100% confidence level,they are connecting points àcrossing points,lower sea points of the six bowelsàfive transport points,confluence points of the eight vesselsàcrossing point,alarm pointàcrossing point,source pointàfive transport points,A total of 15 association rules are obtained for specific points combination,in which the maximum confidence level are GanshuàShenshu(90.57%),GuanyuanàSanyinjiao(90.16%),HeguàSanyinjiao(90.00%).6.Clustering analysis results: Hierarchical clustering was done via SPSS statistics to analyze acupoints.Two major clusterings of main points and matching points are obtained.The main acupoints include TaichongShenmen-Sanyinjiao-Zusanli-Guanyuan,which is consistent with the frequency analysis results,and are commonly used for acupuncture treatment of PMS.The other type is the matching points,including points for syndrome differentiation,points for symptom differentiation,and points based on experience.Syndrome differentiation points such as Zhongwan-FenglongFengchi,Xuehai-Danzhong-Anmian.Symptom differentiation points such as Baihui-Neiguan-Taixi,Shenting-Benshen-Sishencong.Experience based points such as Shenshu-Ganshu-Xinshu-Spleenshu,Feishu-Geshu.Conclusion1.Evaluation of RCT literature on acupuncture treatment of PMS from1990 to 2019.A total of 42 high-quality literatures with a Jadad score of4-7 points are included for Meta analysis.The results indicate that the acupuncture group was significantly better than the control group in improving the total effective rate,Kupperman(KI)score,TCM syndrome,Pittsburgh Sleep Quality Index(PSQI),and Hamilton Depression Scale(HAMD),but show no significant differences in the Menopause Rating Scale(MRS),hot flush score,serum hormone levels,and The Menopause-specific Quality of Life Questionnaire(MENQOL)when compared with the control group.2.Frequency analysis are done for the 140 acupuncture prescription data.The order of the total frequency of acupoint are Sanyinjiao,Taichong,Shenshu,Shenmen,Zusanli,Baihui,Guanyuan,Ganshu,Taixi.Among them,72%are specific points,and the order of frequency are Sanyinjiao,Taichong,Shenmen,Shenshu,Guanyuan,Zusanli,Baihui,Ganshu,Taixi.3.A total of 20 association rules are obtained for the combination of acupoints,including Zigong-Guanyuan,Zigong-Sanyinjiao,Yintang-Baihui,etc.A total of 12 association rules are obtained for the acupuncture location combination,including head-face-neckàlower lim,lumbarbackàlower limb,abdomenàlumbar-back.A total of 21 association rules are obtained for specific points combination,they are connecting pointsàcrossing points,lower sea points of the six bowelsàfive transport points,confluence points of the eight vesselsàcrossing point,alarm pointàcrossing point,source pointàfive transport points,A total of 15 association rules are obtained for specific points combination,they are GanshuàShenshu,GuanyuanàSanyinjiao,HeguàSanyinjiao.4.The result of cluster analysis shows that they are two major clusters:main points and matching points.The main points include Taichong-ShenmenSanyinjiao-Zusanli-Guanyuan,and the matching points include ZhongwanFenglong-Fengchi,Xuehai-Tanzhong-Anmian,Baihui-Neiguan-Taixi,ShentingBenshen-Sishencong,Shenshu-Ganshu-Xinshu-Pishu,Feishu-Geshu,etc.