Dihydroartemisinin inhibits the activation and proliferation of hepatic stellate cells by regulating miR­29b­3p.

Liver fibrosis is an early pathological feature of hepatic diseases. Hepatic stellate cell (HSC) activation and disordered proliferation are associated with liver fibrosis. The present study identified significant differences in the expression levels of microRNA (miRNA/miR)­29b­3p in clinical samples and multiple miRNA databases. Subsequently, the specific antifibrotic mechanism of miR­29b­3p was further elucidated. Reverse transcription­quantitative PCR, western blot, ELISA and immunofluorescence were used to detect the expression levels of target genes and proteins. Oil red O, Nile red and trypan blue staining were used to evaluate HSC activation and cell viability. A luciferase assay was used to detect the relationship between miR­29b­3p and VEGFA. Adhesion, wound healing, apoptosis double staining and JC­1 assays were used to detect the effects of VEGFR1 and VEGFR2 knockdown on HSCs. Immunoprecipitation and fluorescence colocalization were used to identify interactions between the proteins. Furthermore, a rat fibrosis model was constructed to investigate the effects of dihydroartemisinin (DHA) and miR­29b­3p in vivo and in vitro. The results indicated that miR­29b­3p both inhibited the activation of HSCs and limited the proliferation of activated HSCs via lipid droplet recovery and VEGF pathway regulation. VEGFA was identified as a direct target of miR­29b­3p, and knockdown of VEGFA induced cell apoptosis and autophagy. Notably, VEGFR1 and VEGFR2 knockdown both promoted apoptosis; however, VEGFR1 knockdown inhibited autophagy, whereas VEGFR2 knockdown induced autophagy. Furthermore, it was revealed that VEGFR2 regulated autophagy by mediating the PI3K/AKT/mTOR/ULK1 pathway. VEGFR2 knockdown also led to ubiquitination of heat shock protein 60, ultimately inducing mitochondrial apoptosis. Finally, DHA was identified as a natural agonist of miR­29­3p that effectively prevented liver fibrosis in vivo and in vitro. Overall, the present study determined the molecular mechanism by which DHA inhibited HSC activation and prevented liver fibrosis.

Stroke volume variation for predicting responsiveness to fluid therapy in patients undergoing cardiac and thoracic surgery: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the reliability of stroke volume variation (SVV) for predicting responsiveness to fluid therapy in patients undergoing cardiac and thoracic surgery. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, EMBASE, Cochrane Library, Web of Science up to 9 August 2020. METHODS: Quality of included studies were assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. We conducted subgroup analysis according to different anaesthesia and surgical methods with Stata V.14.0, Review Manager V.5.3 and R V.3.6.3. We used random-effects model to pool sensitivity, specificity and diagnostic odds ratio with 95% CI. The area under the curve (AUC) of receiver operating characteristic was calculated. RESULTS: Among the 20 relevant studies, 7 were conducted during thoracic surgery, 8 were conducted during cardiac surgery and the remaining 5 were conducted in intensive critical unit (ICU) after cardiac surgery. Data from 854 patients accepting mechanical ventilation were included in our systematic review. The pooled sensitivity and specificity were 0.73 (95％ CI: 0.59 to 0.83) and 0.62 (95％ CI: 0.46 to 0.76) in the thoracic surgery group, 0.71 (95％ CI: 0.65 to 0.77) and 0.76 (95％ CI: 0.69 to 0.82) in the cardiac surgery group, 0.85 (95％ CI: 0.60 to 0.96) and 0.85 (95％ CI: 0.74 to 0.92) in cardiac ICU group. The AUC was 0.73 (95% CI: 0.69 to 0.77), 0.80 (95% CI: 0.77 to 0.83) and 0.88 (95% CI: 0.86 to 0.92), respectively. Results of subgroup of FloTrac/Vigileo system (AUC=0.80, Youden index=0.38) and large tidal volume (AUC=0.81, Youden index=0.48) in thoracic surgery, colloid (AUC=0.85, Youden index=0.55) and postoperation (AUC=0.85, Youden index=0.63) in cardiac surgery, passive leg raising (AUC=0.90, Youden index=0.72) in cardiac ICU were reliable. CONCLUSION: SVV had good predictive performance in cardiac surgery or ICU after cardiac surgery and had moderate predictive performance in thoracic surgery. Nevertheless, technical and clinical variables may affect the predictive value potentially.