Clinical And Network Pharmacological Study On The Treatment Of Benign Thyroid Nodules (Phlegm-Stasis Interjunction Type) By Xuanbijiejie Solution

Objective : To observe and analyze the clinical effect and possible mechanism of Xuanbijiejie Solution in the treatment of benign thyroid nodule(Phlegm-stasis interjunction type).Methods:1.Patients in the outpatient income group were randomly divided into the treatment group and the control group.Patients in the treatment group were given Xuanbijiejie Solution orally,one course of treatment every 4 weeks and three courses of treatment;The control group received no drug treatment and only regular follow-up according to the Guidelines for 《 Diagnosis and Treatment of Thyroid Nodule and Differentiated Thyroid Carcinoma 》(2012 edition).Both groups had lifestyle interventions.The maximum diameter and number of thyroid nodule,TCM syndrome score,thyroid function and related safety indexes were observed before and after treatment in two groups.The collected data were analyzed statistically.2.Network pharmacological study: The active ingredients and targets of Xuanbijiejie Solution were obtained by computer searching two databases of TCM Pharmacology Database and Analysis Platform(TCMSP)and HERB group Identification database(HERB);Disease targets of benign thyroid were searched in Gene Cards,OMIM and Disgenet databases.Intersection targets were obtained by Venny2.1 software,and Cytoscape3.8.2 was used to construct the network diagram of traditional Chinese medicine,composition and target,and analyze the main active components of Xuanbijiejie Solution.The intersecting targets were substituted into the STRING database to construct the protein-protein interaction(PPI)network diagram.Based on the PPI network diagram,topological analysis was conducted to screen out the key targets.David database was used for GO and KEGG enrichment analysis.Results:After the sample size of this study was removed and dropped off,60 cases were finally studied,including 30 cases in both control group and treatment group.1.The two groups were compared in age,gender,maximum diameter of thyroid nodule before treatment,number of nodule,TCM syndrome scores and other aspects(P > 0.05),indicating comparability.2.Comparison of the maximum diameter and number of thyroid nodules:after treatment,the total effective rate of the reduction of the maximum diameter of nodules in the treatment group was 86.67%,and that in the control group was 6.67%,P < 0.05,showing a difference.In control group,nodule shrinkage was not obvious before and after treatment,P > 0.05;Compared between the two groups,the reduction range of the treatment group was significantly greater than that of the control group,P < 0.05.Number of nodules: The number of thyroid nodules before and after treatment was compared in the treatment group,and the number of thyroid nodules after treatment was lower than that before treatment,P < 0.05,which was statistically significant.In the control group,there was no significant change in the number of nodules after treatment(P > 0.05).The reduction of nodule number in the treatment group was better than that in the control group,P < 0.05.3.Curative effect of TCM syndrome: before and after treatment,the comparison score in the treatment group was significantly decreased,P <0.01,while the control group had no significant difference before and after treatment,P > 0.05.After treatment,the comparison between the treatment group and the control group was P < 0.01,showing statistical significance.4.Safety indicators: All safety indicators before and after treatment were within the normal range,and there were no adverse reactions during the study.5.A total of 75 active ingredients,810 constituent targets,905 BTN disease targets and 160 intersection targets were obtained from Xuanbijiejie Solution.The main active ingredients were naringin,xanthone I,kaempferol,β-ionone,hesperidotam acetate,xanthopyridine B and quercetin.The key targets for treating benign thyroid nodules are STAT3,SRC,PIK3 CA,PIK3R1,MAPK3,AKT1,HSP90AA1,HRAS,PTPN11,ESR1,EP300,VEGFA,EGFR,RELA,JAK2,CREBBP,JUN,STAT1;GO enrichment analysis showed 780 biological processes,74 cell compositions and 173 molecular functions,while KEGG analysis showed 165 pathways.The major pathways include AGE-RAGE,PI3K/AKT,thyroid hormone,cancer pathway and other signaling pathways.Conclusion:1.Through clinical observation,Xuanbijiejie Solution has obvious curative effect on benign thyroid nodules of phlegm-stasis interjunction type.Under the condition of ensuring clinical safety,it can effectively reduce the number of nodules,reduce the size of nodules and improve TCM symptoms.2.The characteristics of multi-target and multi-pathway treatment of benign thyroid nodules by Xuanbijiejie Solution were expounded through network pharmacological study,which opened up ideas for subsequent experimental study and provided scientific basis for clinical application.