| Objective:1.To explore the clinical curative outcomes of individualized acupoint application for opioid-associated constipation.2.To investigate the mechanism of action of acupiontis stiking therapy prescription within the treatment of OIC by network pharmacology and molecular docking methods.Methods:Ⅰ.Clinical trial1.70 patients who met the inclusion criteria for OIC were every which way divided into 2clusters: the observation cluster(n=35)was treated with individualized acupressure and also the comparison cluster(n=35)was treated with lactulose.2.The time to initial evacuation,constipation symptom score,stool form score and adverse reactions were determined in each teams before and once treatment for one week,and followup observation was continued for one week once discontinuance of the drug to know the return of constipation.Ⅱ.Network pharmacology1.The part of network pharmacology: TCMSP database,TCMID database and Chinese natural products chemical composition database were used to find the chemical components of acupoint application prescription,and the relevant literatures were consulted to supplement;The potential targets of chemical ingredients were any foreseen by TCMSP platform and STITCH platform,and the target supermolecule names were remodeled into target sequence names by Uni Prot platform;The targets associated with OIC were screened by Genecards platform,OMIM platform and TTD platform.2.The retrieved potential targets of chemical ingredients were compared with OIC-related targets to obtain common targets,and a "drug-chemical ingredient-intersecting target-disease" relationship network was made by Cytoscape 3.8.2 software.3.The intersectant targets were input into STRIING platform to construct OIC-related PPI network.The PPI network was visualized using Cytoscape 3.8.2 software,and the topology analysis was performed to screen the key targets of OIC treatment by acupressure,and the chemical ingredients corresponding to the key targets were found as the key chemical components.4.Schr?dinger software was applied for molecular docking to verify the reliability of the key chemical ingredients combined with the core target gene;At the same time,enrichment analysis of core target proteins in the DAVID platform to further explore the mechanism of the acupressure formula in treating OIC.Results:Ⅰ.Clinical trial1.Five patients were excluded throughout the treatment period for various reasons,and sixty five cases were finally enclosed,together with thirty three cases within the treatment cluster and thirty two cases within the lactulose cluster.2.Improvement in BSFS and CCS scores(including single items)compared to each teams before the trial(P <0.001).3.After the test,the variations within the simple excreting,kind of excreting aid,duration of each evacuation and number of unsuccessful evacuations per day were not important within the 2 teams(P >0.05).4.When comparing the two groups in terms of time to first evacuation,stool properties,frequency of evacuation,feeling of incomplete evacuation and abdominal pain,the therapeutic effect of acupressure cluster was better(P <0.05).5.Compared to the lactulose cluster,the clinical curative outcomes of the acupressure group were more significant(P <0.05).6.During the trial period,one patient within the acupressure cluster had mild skin allergic reaction,and two patients within the lactulose cluster had nausea,which was alleviated after corresponding treatment.7.The repetition rate of 20.69% was considerably lower within the acupressure cluster than within the lactulose group(47.83%,P <0.05),and also the time to stop repetition was later within the acupressure cluster than within the lactulose cluster(P <0.05).Ⅱ.Network pharmacology1.By analyzing the biological network of the acupressure formula acting on the OIC targets,27 chemical ingredients were found to be the active ingredients of the acupressure formula for the treatment of OIC,and 22 targets were the targets of the acupressure formula for the treatment of OIC.Among them,four major ingredients,namely aloe emodin,luteolin,naringenin and nobilein,and nine key targets,including AKT1,MAPK3,TNF,CREB1 and HMOX1,contend necessary roles within the treatment of OIC by acupressure formula.2.After molecular docking verification,it was found that the key chemical components could combine well with the key targets.3.By PPI network analysis,two groups of protein pairs,AKT1 and TNF,TNF and NOS2,were found to play a crucial role within the treatment of OIC by close interaction.4.By GO functional enrichment analysis,a total of 117 entries associated with biological processes(BP)were screened,and the pathways directly associated with the treatment of OIC were Activation of MAPK activity,regulation of nitric oxide synthase activity,etc.5.A total of 93 relevant entries were obtained by KEGG pathway enrichment analysis screening,chiefly involving TNF,cancer,MAPK and Toll-like receptor signal pathways,etc.Conclusion:1.Both individualized acupoint application and lactulose are effective in the treatment of OIC,and the overall effect of individualized acupoint application is better than that of lactulose;Individualized acupoint application is superior to lactulose in shortening the first defecation time and improving defecation frequency,incomplete defecation and abdominal pain;And individualized acupoint application has low recurrence rate and definite long-run impact within the treatment of OIC.2.This project predicts the effective chemical components and action targets of acupressure formula for the treatment of OIC by the network pharmacology method,and systematically elucidates its mechanism of action,that provides definite data support for its clinical trials. |
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