Systematic review and pathway enrichment analysis of Chinese medicine in preventing recurrence and improving prognosis of cholelithiasis after gallbladder-preserving lithotripsy

Background: Traditional Chinese medicine (TCM) may improve the prognosis management of cholelithiasis patients after gallbladder-preserving lithotripsy. To explore the evidence for this view, we systematically reviewed the efficacy and safety of TCM for improving the prognosis of cholelithiasis after gallbladder-preserving lithotripsy and performed functional pathway enrichment analysis of TCM target genes. Methods: In this systematic review (SRs), we searched six Chinese or international databases to collect randomized controlled clinical trials (RCTs) of TCM in preventing the recurrence of cholelithiasis after gallbladder-preserving lithotripsy. The literature was independently screened by 2 reviewers, who then extracted the data. The Cochrane risk-of-bias and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tools were used to assess the included studies' risk of bias and quality of evidence, respectively. And, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses would be conducted on the TCM prescriptions in the included literature to find the effective component and mechanism of TCM in the prognosis management of gallbladder-preserving lithotripsy. Analysis in this research would be conducted by R 3.5.2 software. Results: A total of 1,024 articles were retrieved, and 9 RCTs involving 926 participants were included after the step-by-step screening. The risk of bias for each important outcome in all the studies was "uncertain". The meta-analysis showed that compared with blank control, TCM prevented cholelithiasis by decreasing the recurrence rate, complications incidence, gallbladder wall thickness, and gallbladder contraction degree. But, there were no significant differences in the rate of the adverse reaction. The result of the GO and KEGG analysis revealed that the mechanism of prevention of TCM in gallstone recurrence may be related to the cholesterol metabolic pathway and that naringin from Glycyrrhiza may be the effective component in the prevention of recurrence. Conclusions: Existing evidence suggests that the use of TCM may reduce the recurrence rate after gallbladder-preserving lithotripsy and this effect may be related to the flavonoid glycoside naringin from Glycyrrhiza uralensis, but more RCTs with high quality in this area may be needed to have a robust conclusion.