Study On The Intervention Effect Of Shudi Tongbian Prescription On Functional Constipation In The Elderly Based On The Changes Of Intestinal Flor

Aim:Systematic evaluate the clinical efficacy and safety of YiQiYangYin recipe in the treatment of elderly constipation.And this paper is to observe the clinical efficacy and safety of treatment of senile functional constipation by using SHUDITONGBIAN recipe.This study is to confirm the effect of SHUDITONGBIAN recipe on intestinal flora in elderly patients with functional constipation.Method:this study includes three parts.1.Systematic evaluation and Meta analysis are used for efficacy of YiQiYangYin recipe in the treatment of elderly constipation.The main method is to use computer retrieval from databases such as China biology medicine disc(CBMdisc),Chinese national knowledge inf-rustracter(CNKI),WanFang medical database,Weipu database,PubMed,Cochrane Library,EMbase,and so on,while the searching time is from the start of the database to March 1,2018.And relative literature,in the past two years,from World Chinese Journal of Digestology,Chinese Journal of Integrated traditional and Western medicine on digestion,China Journal of Traditional Chinese medicine and pharmacy,Journal of traditional Chinese medicine,Chinese Journal of integrated Traditional and Western medicine have been manually retrieve.The clinical randomized controlled trials(RCT)on the treatment of elderly constipation by using YiQiYangYin recipe have been selected.The data were extracted and the quality of literature was evaluated according to the standard of Cochrane Handbook 5.1.And RevMan 5.3 software was used to meta analyze the extracted data.2.Clinical observation on the therapeutic effect of treating senile functional constipation(qi and Yin deficiency type)with the decoction of YiQiYangYin recipe.Open and randomized contrast method was used.There have two groups.The sample size of each group was 30 cases,a total of 60 cases.The included cases were from elderly patients with functional constipation in outpatient and inpatient,and informed consent was signed.Sixty patients were randomly divided into treatment group and contrast group with 30 cases in each group by SAS software generated by computer.Patients in the treatment group were treated with taking SHUDITONGBIAN recipe,decocted in the pharmaceutical room of our hospital,150ml*2 bags,one bag twice a day,and taken orally in the morning and evening.Patients in the contrast group were given lactulose orally,30ml/day,in two doses,and the maintenance dose was 30ml/day,take twice one day.The drugs were taken at 0 week 0,1th week,2th week,3th week and 4th week for a total of 4 weeks.Observation time points and efficacy indexes:efficacy evaluation was conducted before treatment,1 week,2 weeks,3 weeks and 4th weeks.Safety indexes:once at 0 and once at the 4 week,and should be examined within 1 week before and 1 week after drug withdrawal.Adverse reactions should be closely observed and recorded.Efficacy evaluation was conducted,including comprehensive efficacy evaluation of constipation symptoms,efficacy evaluation criteria of TCM syndromes,and quality of life scale for constipation patients(PAC--QOL).To evaluate the clinical safety of the drug.3.The therapeutic effect of t treating senile functional constipation(qi and Yin deficiency type)with the decoction of YiQiYangYin recipe.This was divided into two experiments.Fresh feces of 30 constipation patients and 10 healthy people before and after intervention in the treatment group were collected.The intestinal flora difference between 10 healthy people and 10 constipation patients and the intestinal flora difference between 30 constipation patients before and after intervention were analyzed.Using Illumina Hiseq2500 high-throughput sequencing platform,the 16srDNA gene of fecal samples was analyzedVariant regions are compared with gene libraries,and data are subjected to OTU clustering and species annotation,Alpha system analysis,Beta diversity analysis,difference analysis,etc.Results:1.A total of 44 studies involving 4173 elderly constipation patients were included.The quality of the study included is generally low.Meta analysis results show:Compared with the cathartic,YiQiYangYin recipe could reduce the recurrence rate of the elderly constipation(RR=0.35;95%CI=[0.17,0.72]),Compared with the prokinetic agents,YiQiYangYin recipe can obviously improve the clinical cure rate(RR=1.48;95%CI=[1.23,1.79]);Compared with the comprehensive western medicine,YiQiYangYin recipe can reduce the recurrence rate of the elderly constipation(RR=0.16;95%CI=[0.09,0.30]),but the clinical cure rate of the two is equivalent(RR=1.35;95%CI=[0.99,1.85]);Compared with the Chinese patent medicine,there was no significant difference in the recurrence rate(RR=0.42;95%CI=[0.07,2.37]).However,the YiQiYangYin recipe could increase the clinical cure rate(RR=1.39;95%CI=[1.23,1.57]).The adverse effects rate of YiQiYangYin recipe is lower than other method.2.Clinical efficacy observation.In terms of constipation symptom score,the treatment group was superior to the contrast group in terms of falling,exhaustion,bloating(P=0.022).In terms of improvement of traditional Chinese medicine(TCM)syndrome points,total points of TCM syndrome points,physical fatigue,dry mouth and pharynx,the treatment group,Short breath,staying and eating less was better than the control group(P<0.05).In terms of improvement of the quality of life scale(PAC--QOL)for constipation patients,there was no difference in satisfaction between the treatment group and the contrast group.The total score of the scale,physical discomfort,psychosocial discomfort,worry and anxiety were better in the treatment group than in the control group(P<0.05).Efficacy evaluation:comprehensive efficacy evaluation of constipation symptoms,treatment group,significant effect in 11 cases,effective in 13 cases,ineffective in 4 cases,total effective rate of 85.7%.The total effective rate was 65.5%.TCM syndrome efficacy evaluation standard,TCM group,clinical cure 2case,obvious effect 14 cases,effective 12 cases,ineffective 0 cases,the total effective rate of 100%.The quality of life scale(PACQOL)for constipation patients was assessed,in the treatment group,with 0 cases of significant effect,11 cases of effective effect,and 17 cases of ineffective effect,with a total effective rate of 39.3%.There was no statistical significance between the two groups,P>0.05.Safety evaluation:based on objective evaluation,this study truly recorded adverse events during the study.In the control group,1 patient was discontinued due to obvious abdominal distension,while in the treatment group,no patient was discontinued due to adverse test.It indicated that the method of defecation was safe.3.Experimental research3.1 difference analysis of intestinal flora between healthy population and elderly functional constipation population.It can be seen from the experiment that the healthy group and the constipation group are mainly composed of four phylum horizontal species,namely Firmicutes,Bacteroidetes,Proteobacteria and Actinobacter.In the same group of samples,the abundance of bacterial communities in phylum,class,order,family and genus had good aggregation,indicating that the abundance of bacterial communities in the healthy group and the constipation group had certain differences.Alpha diversity analysis shows that the sequencing amount is sufficient,and increasing the sequencing amount cannot provide more new OTU species with rich composition and high uniformity.There are enough samples,and the current sample size can reflect the vast amount of microbial species information in the sample.The abundance and evenness of species in healthy group were higher than those in constipation group.Beta diversity analysis:distance matrix thermogram,PCoA analysis and PCA analysis show that there are differences between the two groups,but the differences are not significant.Analysis of differences shows that there are certain differences between the two groups.All the different species came from Sclereida.3.2Effect of Shudi Tongbian Recipe on Changes of Intestinal Flora before and after Functional Constipation in Elderly Patients.Species structure analysis showed that the intestinal flora of the middle-aged and elderly constipation patients were mainly Firmicutes,Bacteroidetes,Proteobacteria and Actinomycetes Four major phyla are dominant.In the experiment,it was found that Bifidobacterium and Akkermansia Christensellaceae in the "extremely long-lived core microorganism group" all changed after treatment.Bifidobacterium showed a significant increase,with a significant statistical difference(P=0.00999).In this experiment,in the family Enterobacteriaceae,Escherichia-Shigella、Citrobacter、Enterobacter、Klebsiella,these harmful bacteria have a downward trend in profitability after treatment,although there is no statistical difference.Species have similar colony abundance in phylum,class,order,family and genus,and there is little difference in colony abundance before and after treatment.According to the OTU Vestigo between the two groups,the distribution of flora before and after treatment is approximately the same.The difference between the two groups is small.After treatment,there are 10 OTU less than before treatment.Except Ruminococcaceae,other bacteria are conditioned pathogens.After treatment with traditional Chinese medicine,more harmful flora disappear.Although the difference is not statistically significant,it can explain to some extent that traditional Chinese medicine has certain inhibitory effect on the growth of harmful microorganisms.Alpha diversity analysis shows that the sequencing amount is sufficient,and increasing the sequencing amount cannot provide more new onesOTU.The species composition is rich,the uniformity is high,the samples are enough,the current sample size can reflect the vast majority of microbial species information in the samples,and the species abundance is similar before and after treatment.Beta diversity analysis:the distance matrix heat map,PCoA analysis and PCA analysis showed no significant difference between the two groups.Variance analysis.LEfSe analysis showed that before and after treatment,there were significant differences in species abundance of bifidobacteriae,class,order,family,genus and five layers.This indicated that Chinese medicine could significantly improve the abundance of bifidobacterium.MetaStats analysis showed that MetaStats presented no significant difference between the two groups at phylum,class,order,family and genus before and after treatment.Conclusions1.Yiqi Yangyin Recipe can improve the clinical recovery rate and reduce the recurrence rate of senile constipation patients,and has good clinical safety.However,due to the generally low quality of the included research,more high-quality clinical evidence-based evidence is needed to verify it.2.There are some differences in species abundance between healthy people and elderly constipation people.Abundance of beneficial bacteria increases in healthy people and conditional pathogenic bacteria increases in elderly patients with functional constipation.3.There was no significant difference in species richness after the intervention of TCM Zhudi Biantong Formula,which indicated that intestinal flora tended to be stable and did not fluctuate significantly.Intestinal homeostasis is beneficial to the host.Traditional Chinese medicine has no side effects on intestinal microbial homeostasis.The traditional Chinese medicine prescription for relieving constipation significantly increases the abundance of bifidobacteria in elderly patients with functional constipation,and has a tendency to increase the beneficial bacteria population of Akkermansia and Christensenellaceae,reducing the enterobacteriaceae flora,Eubacterium,Erysipelotrichaceae,Megasphaera,Gastranaerophillaes,TCM Zhudibiantong Formula can improve the abundance of beneficial bacteria of Bifidobacterium,so as to achieve the goal of regulating the intestinal environment.Whether intestinal flora can be regulated in two directions requires further multi-center and large-sample studies.