Objective To investigate the mRNA expressions of liver X receptor α (LXRα), farnesoid X receptor (FXR), steroid xenobiotic receptor (SXR) and liver receptor homolog 1 (LRH-1) gene in patients with cholesterol gallstone (CGS) disease in order to elucidate the biomolecular pathogenesis of gallstone formation. Methods Twenty-seven patients with CGS (CGS group) and 10 controls without gallstones (control group) were included in this study. Serum lipid composition (total cholesterol, triglyceride, high density lipoprotein cholesterol, apoprotein B, apoprotein A1), gallstone cholesterol concentration and biliary composition (cholesterol, bile salts, lecithin) were assayed. Biliary total lipid and cholesterol saturation index (CSI) were calculated. mRNA expressions of LRH-1, FXR, SXR and LXRα gene were determined by real-time polymorphism chain reaction. Results Serum high density lipoprotein cholesterol concentration was lower in CGS group than that in control group 〔(0.93±0.05) mmol/L vs (1.33±0.09) mmol/L, P＜0.001〕 and serum apoprotein A1 was also lower in CGS group than that in control group 〔(1.19±0.05) g/L vs (1.36±0.06) g/L, P＜0.05〕. There were no differences in serum total cholesterol, triglyceride and apoprotein B between two groups (Pgt;0.05). CSI was higher in CGS group than that in control group (1.17±0.02 vs 0.79±0.10), P＜0.001. Biliary cholesterol was also higher in CGS group than that in control group 〔(7.96±0.39) mol% vs (5.26±0.89) mol%, P＜0.01〕, while biliary total lipid was lower in CGS group than that in control group 〔(104.72±10.51) g/L vs (154.24±14.20) g/L, P＜0.05〕. There were no differences in bile salts and lecithin between two groups (Pgt;0.05). Expression of LRH-1 gene was higher in CGS group than that in control group (14.18±1.80 vs 7.22±2.22), the difference was statistically significant (P＜0.05). There were no differences in mRNA expressions of LXRα, FXR and SXR gene between two groups (Pgt;0.05). Conclusion CGS disease may be related to increased expression of LRH-1 gene.
In 2014, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group published guidance in BMJ to evaluate the certainty of the evidence (confidence in evidence, quality of evidence) from network meta-analysis. GRADE working group suggested rating the certainty of direct evidence, indirect evidence, and network evidence, respectively. Recently, GRADE working group has published a series of papers to improve and supplement this approach. This paper introduces the frontiers and advancement of GRADE approach to rate the certainty of evidence from network meta-analysis.