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Background and Aim: The role of C6ORF120 in promoting CCL4‐induced hepatic fibrosis and its possible mechanisms were explored in C6orf120 knockout rats (C6orf120−/−) and LX‐2 cells (a type of human hepatic stellate cell line). Methods: In vivo experiments, wild‐type and C6orf120−/− rats were used to investigate the function of C6ORF120. In the in vitro experiments, C6ORF120 recombinant protein (rC6ORF120) at a concentration of 200 ng/mL was used to stimulate LX‐2 cells. Sirius Red staining, Masson staining, western blotting, polymerase chain reaction, immunohistochemistry, and immunofluorescence were used to explore fibrosis‐associated factors. Results: C6orf120−/− rats showed mild fibrosis and liver injury in the CCL4‐induced liver fibrosis model. Furthermore, RNA‐seq revealed that C6orf120−/− rats had less extracellular matrix deposition and activated stellate cells. Consistent with the in vivo, the rC6ORF120 induced LX‐2 cell activation. Moreover, mechanistic studies revealed that the p‐PI3K/PI3K, p‐Akt/Akt, and p‐mTOR/mTOR levels were significantly elevated and LY294002 (a PI3K/Akt/mTOR typical pathway inhibitor) reversed the function of C6ORF120 in activating LX‐2 cells. Conclusion: C6ORF120 could activate hepatic stellate cells and promote hepatic fibrosis via the PI3K/Akt/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Dual anti-retroviral therapy is the main proven valuable intervention type for treating naïve HIV/AIDS. Currently, no high-quality evidence is available regarding the best dual schemes.Objectives: The aim of this study is to evaluate the effectiveness and safety of PIs/r-based dual therapy in treatment-naïve HIV/AIDS patients by using network meta-analysis.Methods: Randomized controlled trials of PIs/r-based dual therapy in treatment-naïve HIV/AIDS were searched based on Embase, PubMed and Cochrane library database from January 2006 to June 2021. Taking viral suppression rate, CD4+T cell count changes from baseline as the primary indicator and adverse events rate as secondary indicator, the network meta-analysis was performed on Review Manager and STATA software. Heterogeneity was assessed by the Q statistic and I2. We registered our protocol in Prospero with ID CRD42021275466.Results: Among 15 randomized controlled trials (3,497 patients and 7 PIs/r-based dual therapy) were reviewed in this study. According to the forest map, DRV/r + INSTIs was more effective compared to triple therapy (TT) in viral suppression [OR 0.82, 95% CI (0.61–1.11)], in CD4+T cell count changes from baseline [MD 1.9, 95% CI (0.7, 3.1), I2 86%], in adverse events [OR 0.98, 95% CI (0.68–1.39)]. Furthermore, SUCRA ranking analysis indicated that DRV/r + INSTIs was superior to TT in viral suppression (DRV/r + INSTIs 75.5% > TT 41.2%) and in immune construction (DRV/r + INSTIs 67% > TT 42%). In addition, DRV/r + INSTIs was similar to TT in adverse events (DRV/r + INSTIs 54.9% ≈ TT 54.7%).Conclusion: DRV/r + INSTIs was obviously superior to TT in viral suppression and immune reconstruction, and was not higher than TT in adverse events.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42021275466

Aim: This meta-analysis aimed to assess the precision of Sonazoid contrast-enhanced ultrasound (CEUS) to distinguish hepatocellular carcinoma (HCC) from focal liver lesions (FLLs)., Material and Methods: The Cochrane Library, Embase, PubMed, and Web of Science databases were systematically searched and checked for studies using Sonazoid CEUS to characterize HCC. A comprehensive meta-analysis was conducted, involving data pooling, subgroup analyses, meta-regression, and investigation of publication bias., Results: The meta-analysis included fourteen studies. The overall diagnostic accuracy for characterizing HCC was as follows (all ranges show the 95% confidence interval): pooled sensitivity of 0.87 (0.80-0.92), pooled specificity of 0.95 (0.91-0.97), and a diagnostic odds ratio of 121 (61-241). The overall weighted area under the curve was 0.97 (0.95-0.98). The pooled sensitivity, specificity, and diagnostic odds ratio for Sonazoid and Sonovue were 0.75 (0.63- 0.84), 0.97 (0.86-0.99), 82 (15-445); and 0.64 (0.51-0.76), 0.98 (0.91-0.99), 72 (17-311), respectively. The sources of heterogeneity were identified as the study location, prevailing risk factor, reference diagnosis standard, criteria of Sonazoid CUES, and the proportion of cases of HCC. We observed no potential publication bias., Conclusion: Sonazoid CEUS is efficient to distinguish HCC from FLLs, with good sensitivity and specificity. It is comparable to Sonovue CEUS to diagnose HCC.