Research On The Clinical Efficacy And Mechanism Of Traditional Chinese Medicine In The Treatment Of Tic Disorder Of Spleen Deficiency And Liver Hyperactivity

Tic disorder(TD)is a common neuropsychiatric disease that starts in pre-school and school-age period.It is usually characterized by involuntary,repeated,arrhythmic and rapid muscle movement and vocal twitch,and can be accompanied by behavioral symptoms such as inattention and hyperactivity.According to literature reports,there are more than 10 million children with TD in China."The complete collection of ancient and modern medicine"says that"the spleen and soil are weak,and the liver and wood ride it,so the tendons contracture and twitch."In recent years,there are many academic thoughts on the treatment of tic disorders based on liver and spleen,and the effect is remarkable.This study further explored the clinical efficacy and mechanism of traditional Chinese medicine(TCM)in the treatment of tic disorder of spleen deficiency and liver hyperactivity by using systematic evaluation,self-control study and network pharmacology.Study 1:Systematic evaluation of TCM in the treatment of tic disorder of spleen deficiency and liver hyperactivityObjective To systematically evaluate the efficacy and safety of TCM in the treatment of TD with spleen deficiency and liver hyperactivity by meta-analysis,and to provide evidence-based evidence for the treatment of TD with TCM.Methods 1.Screening criteria:the research type is randomized controlled trial(RCT)of TCM in the treatment of TD.The subjects of the study were children with TD diagnosed as spleen deficiency and liver hyperactivity.The diagnostic basis was based on Pediatrics of Traditional Chinese Medicine,Diagnostic and statistical manual of mental disorders fifth edition(DSM-5),Chinese Mental Disorders and Diagnostic Criteria,3rd Edition(CCMD-3),etc;In terms of intervention measures,the experimental group was treated with TCM and the control group was treated with western medicine;The outcome measures were the effective rate of Yale global tie severityb scale(YGTSS)and adverse reaction rate before and after treatment.2.Retrieval Strategy:RCT literatures about TCM treatment of tic disorders were searched in Chinese and English databases.Chinese databases are mainly CNKI,VIP,Wanfang and CBM,while foreign databases are PubMed,Cochrane Library and EMBASE.The retrieval time limit is from January 1,2000 to January 1,2021.3.Literature was screened according to inclusion and exclusion criteria,and data were extracted.4.RevMan5.3 software and Stata15.1 software were used for methodological quality evaluation and meta-analysis.Results A total of 1131 literatures were retrieved,and 14 literatures were finally included.A total of 1169 children with TD were recorded,including 670 in the experimental group and 499 in the control group.The results of meta-analysis showed that the effective rate of TCM in the treatment of TD with spleen deficiency and liver hyperactivity(RR=1.13,95%CI=[1.07,1.19],P=0.000)was better than that of western medicine,and the incidence of adverse reactions(RR=0.23,95%CI=[0.10,0.50],P=0.0002)was lower than that of conventional western medicine.Conclusion The effective rate of TCM in the treatment of TD with spleen deficiency and liver hyperactivity is better than that of western medicine,and the incidence of adverse reactions is lower than that of western medicine.This conclusion provides evidence for the following clinical research of this subject.Study 2:Clinical effect of TCM on TD of spleen deficiency and liver hyperactivityObjective To analyze the effectiveness of director Bai’s self-made prescription(tiaogan Jianpi prescription)in the treatment of TD of spleen deficiency and liver hyperactivity by collecting and sorting out the outpatient cases of director Bai.Methods The outpatient cases of director Bai were collected and sorted out for self-control study.The score reduction rate of YGTSS scale was taken as the main observation index.The effectiveness of tiaogan Jianpi Recipe was analyzed after 4 weeks of treatment.The enrolled children were followed up after 2 months of withdrawal.Results After treatment with tiaogan Jianpi Recipe for 4 weeks,there were no adverse reactions in the enrolled children.According to the curative effect standard:after the course of treatment,4 cases of tic symptoms were clinically controlled,21 cases were significantly effective,13 cases were effective and 2 cases were ineffective.The total effective rate was 95%.There were significant statistical differences in YGTSS score and TCM syndrome score before and after treatment.It proves that tiaogan Jianpi Recipe is effective and safe in the treatment of TD with spleen deficiency and liver hyperactivity.Conclusion Tiaogan Jianpi Recipe is effective,safe and reliable in the treatment of TD with spleen deficiency and liver hyperactivity.It can be further studied in the future to provide new ideas for the treatment of clinical TD.Study 3:To explore the active ingredients and mechanism of Tiaogan Jianpi prescription in treating TD based on network pharmacologyObjective To explore the effective components and mechanism of tiaogan Jianpi Recipe in the treatment of TD based on network pharmacology.Methods The effective ingredients and their action targets of the prescription(tiaogan Jianpi Recipe)prepared by Director Bai were screened by TCMSP,TCMID,NPASS and ADME.Cytoscape3.9.0 software was used to construct a TCMcomponent-target network diagram.TD disease targets were retrieved from TTD,gene cards,drugbank and OMIM databases.After correcting all targets through UniProt database,excel table is used to obtain the intersection targets of disease and drugs,and the protein-protein interaction(PPI)network is constructed based on string platform.Import PPI network into cytoscape3 9.0 software,cluster analysis was carried out through molecular complex detection(mcode)components to speculate the core target gene of tiaogan Jianpi Recipe.At the same time,the intersection targets were imported into metascape database for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and genomes(KEGG)enrichment analysis.Use Cytoscape 3 9.0 software to draw the network diagram of active components-target action-pathway.Results After searching,7 active components of Gastrodia elata,32 active components of uncaria,1 active component of Bombyx Batryticatus,4 active components of cicada molting,2 active components of scorpion,13 active components of bupleurum,8 active components of Paeonia alba,6 active components of Poria cocos,4 active components of Atractylodes macrocephala and 88 active components of licorice were extracted,which acted on 274 target genes together.1215 TD-related target genes were collected.There were 87 intersection target genes between active ingredients and TD.The PPI network of intersecting genes contained 87 nodes,815 edges and an average node degree of 18.7.PPI network was imported into Cytoscape3.9.0 software,and cluster analysis was carried out by MCODE component,and 33 core target genes of Tiaogan jianpi recipe were predicted.GO and KEGG enrichment analysis results showed that Tiaogan Jianpi formula played a role in the treatment of TD based on 1301 biological processes,88 cellular components,149 molecular functions and 158 signaling pathways.Conclusion It is predicted that Tiaogan jianpi recipe can regulate neuroactive ligand-receptor interaction,calcium signaling pathway,dopaminergic synapse and other signal pathways through key targets such as ESR1,CHRM1,ADRA1B,CHRM3,OPRM1,so as to play a role from multiple dimensions,such as regulating the activities of neurotransmitters such as dopamine,norepinephrine and 5-hydroxytryptamine,and binding of cytokine receptors.