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.

Identification of a 5-lncRNA-Based Signature for Immune Characteristics and Prognosis of Lung Squamous Cell Carcinoma and Verification of the Function of lncRNA SPATA41.

Lung squamous cell carcinoma (LUSC) is one of the most lethal cancers worldwide. Traditional tumor-node-metastasis (TNM) staging system has many insufficiencies in predicting immune characteristics, overall survival (OS), and prognosis of LUSC. LncRNA is currently found involved in tumor development and effectively predicts tumor prognosis. We screened potential tumor-related lncRNAs for immune characteristics and constructed a nomogram combining lncRNA and traditional clinical indicators for prognosis prediction. We obtained the large-scale gene expression profiles of samples from 492 LUSC patients in The Cancer Genome Atlas database. SPATA41, AL034550.2, AP003721.2, AC106786.1, and AC078889.1 were finally screened to construct a 5-lncRNA-based signature. The risk score of the signature divided patients into subgroups of high-risk and low-risk with significant differences in OS. Their area under the curve (AUC) reached more than 0.70 in 1, 3, and 5 years. In addition, compared with the high-risk subgroup, the low-risk subgroup exhibited a remarkably favorable prognosis and TME score, along with a higher immune infiltration score and lower TIDE score. The signature also significantly related to chemotherapy response, especially in cisplatin, vinorelbine, and paclitaxel. Importantly, the nomogram we constructed had good reliability with the assessment of the calibration chart and consistency index (c-index). GO and KEGG enrichment analysis indicated that co-expression mRNAs of the 5 lncRNAs were mainly focused on RNA splicing, DNA replication, and protein serine/threonine kinase activity. Functional assays demonstrated that SPATA41, one of the five OS-related lncRNAs, regulated invasion, migration, proliferation, and programmed death in vitro. In summary, our 5-lncRNA-based signature has a good performance in predicting immune characteristics and prognosis of LUSC patients.

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.

Efficacy and safety of paravertebral block versus intercostal nerve block in thoracic surgery and breast surgery: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the analgesic efficacy and safety of paravertebral block (PVB) versus intercostal nerve block (INB) in thoracic surgery and breast surgery. METHODS: The PubMed, Web of Science, Embase and the Cochrane Library were searched up to February 2020 for all available randomized controlled trials (RCTs) that evaluated the analgesic efficacy and safety of PVB compared with INB after thoracic surgery and breast surgery. For binary variables, odds ratio (OR) and 95% confidence interval (CI) was used. For continuous variables, weighted mean difference (WMD) and 95% confidence interval (CI) were used. RevMan5. 3 and Stata/MP 14.0 were used for performing the meta-analysis. RESULTS: A total of 9 trials including 440 patients (PVB block:222 patients; INB: 218 patients) met the inclusion criteria. In the primary outcome, there was no significant differences between the two groups with respect to postoperative visual analogue scale (VAS) at 1h (Std. MD = -0. 20; 95% CI = -1. 11to 0. 71; P = 0. 66), 2h (Std. MD = -0. 71; 95% CI = -2. 32to 0. 91; P = 0. 39), 24h (Std. MD = -0. 36; 95% CI = -0. 73 to -0. 00; P = 0. 05) and 48h (Std. MD = -0. 04; 95% CI = -0. 20 to 0. 11; P = 0. 57). However, there was significant difference in VAS of non Chinese subgroup at 1h (Std. MD = 0. 33; 95% CI = 0. 25to 0. 41; P<0. 00001) and VAS of Chinese subgroup at 24h (Std. MD = -0.32; 95% CI = -0.49 to-0.14; P = 0.0003). In the secondary outcome, the analysis also showed no significant difference between the groups according to the rates of postoperative nausea and vomit (OR = 0. 63; 95% CI = 0. 38 to 1. 03; P = 0. 06) and the rates of postoperative additional analgesia (OR = 0. 57; 95% CI = 0. 21 to 1. 55; P = 0. 27). There was significant difference in postoperative consumption of morphine (Std. MD = -14. 57; 95% CI = -26. 63 to -0.25; P = 0. 02). CONCLUSION: Compared with INB, PVB can provide better analgesia efficacy and cause lower consumption of morphine after thoracic surgery and breast surgery.