Exploration and validation of the prognostic value of RNA-binding proteins in hepatocellular carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Increasing evidence suggests that the dysregulation of RNA-binding proteins (RBPs) is involved in the development of various cancers. However, there is a paucity of studies investigating the roles of RBPs in HCC. MATERIALS AND METHODS: Data on HCC samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases (available at: www.ncbi.nlm.nih.gov/geo), and data regarding human RBPs were integrated from SONAR, XRNAX, and CARIC results. We identified modules associated with prognosis using weighted gene co-expression network analysis (WGCNA) and performed functional enrichment analysis. Univariate and least absolute shrinkage and selection operator (LASSO) regression analyses were used to identify prognostic RBPs and establish a prediction model. According to the median risk score, we separated patients into high- and low-risk groups and investigated the differences in immune cell infiltration, somatic mutations, and gene set enrichment. Univariate and multivariate regression analyses were used to identify prognostic factors for HCC. A nomogram was constructed, and its performance was evaluated with calibration curves. RESULTS: Sixteen RBPs (MEX3A, TTK, MRPL53, IQGAP3, PFN2, IMPDH1, TCOF1, DYNC1LI1, EIF2B4, NOL10, GNL2, EIF1B, PSMD1, AHSA1, SEC61A1, and YBX1) were identified as prognostic genes, and a prognostic model was established. Survival analysis indicated that the model had good predictive performance and that a high-risk score was significantly related to a poor prognosis. Additionally, there were significant differences in immune cell infiltration, somatic mutations, and gene set enrichment between the high- and low-risk groups. Univariate and multivariate regression analyses indicated that the RBP-based signature was an independent prognostic factor for HCC. The nomogram based on 16 RBPs performed well in predicting the overall survival of HCC patients. CONCLUSIONS: The RBP-based signature is an independent prognostic factor for HCC, and this study could provide an innovative method for analyzing prognostic biomarkers and therapeutic targets for HCC.

Percutaneous revascularization for atherosclerotic renal artery stenosis: a meta-analysis.

OBJECTIVE: This study investigates whether medication therapy alone is as effective and safe as percutaneous revascularization (PR) in patients with atherosclerotic renal artery stenosis (ARAS). MATERIALS AND METHODS: The Embase, PubMed, and Cochrane Library databases were searched from their inception to July 31, 2021, for randomized controlled trials (RCTs) reporting PR for ARAS. RevMan 5.3 was employed to analyze the retrieved articles. RESULTS: Eight studies with a total of 2,225 ARAS patients were included in this analysis, demonstrating that PR and medication therapy alone had a similar effect on both systolic [mean difference (MD)= 0.19, 95% CI: -1.64- 2.02] and diastolic blood pressure (MD= -0.44, 95% CI: -1.68-0.80). Meanwhile, there were no differences in all-cause mortality [Odds ratio (OR) = 0.89, 95% CI: 0.70-1.14], stroke (OR = 0.84, 95% CI: 0.55-1.31), congestive heart failure (OR = 0.89, 95% CI: 0.67-1.19), and perioperative complications (OR = 0.87, 95% CI: 0.68-1.12). CONCLUSIONS: Medication therapy alone is as effective and safe as PR.

Prediction of active ingredients and mechanism of Siwei Jianbu decoction in the treatment of atherosclerosis by network pharmacology.

OBJECTIVE: Siwei Jianbu Decoction (SJD) has been shown to be effective in treating atherosclerosis (AS). However, its mechanism is still unclear. MATERIALS AND METHODS: The active compounds and targets of SJD were identified from the Traditional Chinese Medicine System Pharmacology (TCMSP) database. The target genes of AS were obtained from the Online Mendelian Inheritance in Man (OMIM), GeneCards, DrugBank, and Therapeutic Target (TTD) databases. Interactions between drug and disease targets were analyzed to obtain common targets. Subsequently, "herb-compound-target" and protein-protein interaction (PPI) networks were constructed and analyzed using the Cytoscape software. Thereafter, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed by DAVID online database. Then, the results were visualized by R software. Finally, molecular docking was performed using AutoDockTools and PyMOL software. RESULTS: A total of 61 active compounds and 377 target genes were identified for SJD, as well as 726 target genes for AS. Interactive analyses revealed 126 common genes between SJD and AS. Quercetin, ellagic acid, baicalein, and kaempferol were the 4 key compounds in SJD. Moreover, eight key targets, namely TNF, SRC, RELA, AKT1, STAT3, JUN, MAPK1 and FOS were found. Results from enrichment analysis indicated that the MAPK pathway may play an important role. The analysis of molecular docking revealed that the key compounds formed strong bonds with their corresponding key targets. CONCLUSIONS: These findings indicate that SJD could prevent AS by inhibiting the expression of genes associated with MAPK pathway such as MAPK1, RELA, and FOS.

[Association studies between postoperative hypoeosinophilia and hospital stay in patients undergoing hip fracture surgery under different anesthesia].

Objective: To investigate early postoperative changes in eosinophils (EOS) and the relationship of postoperative hospital stay and hypoeosinophilia in patients undergoing hip fracture surgery under general or spinal anesthesia. Methods: The clinical data of patients who underwent hip fracture surgery at Beijing Tiantan Hospital between April 2014 and November 2017 were retrospectively analyzed. Patients were classified according to whether they received general anesthesia or spinal anesthesia. Univariate regression analysis was used to examine a number of covariates potentially contributed to postoperative hospital stay. Multivariate linear regression was used to analyze the relationship between postoperative day 1 EOS counts and postoperative hospital stay. Interaction and stratified analyses were conducted according to anesthesia methods. Results: A total of 149 patients were included in this study. Thirty-four of them underwent general anesthesia and 115 of them underwent spinal anesthesia. The postoperative day 1 EOS of the general anesthesia group was 0 (0,1.8)×107/L, which was lower than that of the spinal anesthesia group 1.0(0,6.0)×107/L (Z=3.095, P<0.01). After adjusting the confounders of age, gender, American Society of Anesthesiologists (ASA) grade, intraoperative blood loss, intraoperative red blood cell (RBC) transfusion, postoperative day 1 hematocrit (HCT) and white blood cell (WBC), postoperative complications, and the interaction terms for ASA, intraoperative blood loss, intraoperative RBC transfusion and postoperative complications, the negative correlation between postoperative hospital stay and postoperative day 1 EOS level was significant (ß=-0.39, 95%CI:-0.74--0.05, P<0.05) in the general anesthesia group. Conclusion: EOS were significantly decreased after surgery in general anesthesia group, and the postoperative hospital stay was negatively correlated with postoperative day 1 hypoeosinophilia.

[Expressions of the key proteins of the protein kinase B/mammalian target of rapamycin signaling pathway in skin tissue and wound tissue of diabetic rats].

Objective: To explore the changes in the expressions of key proteins of the protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling pathway in skin tissue and wound tissue of diabetic rats, and to elucidate the associated mechanisms. Methods: Seventy-eight SD rats aged from 7 to 8 weeks were divided into diabetes group and non-diabetes group according to the random number table, with 39 rats in each group. Rats in diabetes group were intraperitoneally injected with 20 mg/mL streptozotocin fluid in the dose of 65 mg/kg (dissolved in citrate buffer solution) for once to establish the model of diabetes mellitus. Rats in non-diabetes group were injected with the equivalent volume of citrate buffer solution in the same way. Three rats of each group were respectively selected in each week from post injection week (PIW) 1 to 8 for collection of full-thickness skin samples on the back with area approximately of 1.0 cm×1.0 cm to determine epidermal thickness with HE staining. Fifteen rats of each group were inflicted with full-thickness skin defect by resection of skin as above in PIW 1. Three rats of each group were respectively sacrificed immediately after injury and on post injury day (PID) 1, 3, 5 and 7. One piece of skin tissue around the wound edge in each rat was cut off immediately after injury, and wound tissue in each rat was cut off from PID 1 to 7. One part of the tissue was used for determination of protein expression levels of Akt, phosphorylated Akt, mTOR, and phosphorylated mTOR in skin tissue and wound tissue with Western blotting. Surplus tissue was used for observation of expressions of phosphorylated Akt and vimentin in skin tissue and wound tissue with immunofluorescent staining. Data were processed with analysis of variance of factorial design and multiple t test. Results: (1) The epidermal thicknesses in rats between the two groups were similar in PIW 1 and 2 (with t values respectively 0.25 and 1.33, P values above 0.05). From PIW 3 on, the epidermal thicknesses were significantly thinned in rats of diabetes group as compared with those of non-diabetes group (with t values from 4.44 to 9.71, P<0.05 or P<0.01). (2) Compared with those in skin tissue immediately after injury, the protein expression levels of Akt, phosphorylated Akt, mTOR, and phosphorylated mTOR in wound tissue of rats in non-diabetes group were increased remarkably from PID 1 to 7 (except for mTOR on PID 3, with t values from 3.75 to 21.44, P<0.05 or P<0.01). Compared with those in skin tissue immediately after injury, the protein expression levels of Akt and mTOR in wound tissue of rats in diabetes group were not significantly changed from PID 1 to 7 (except for mTOR on PID 1, with t values from 0.03 to 2.32, P values above 0.05), but the protein expression levels of phosphorylated Akt and phosphorylated mTOR in wound tissue were increased remarkably from PID 1 to 7 (except for phosphorylated Akt on PID 1, with t values from 3.79 to 8.11, P<0.05 or P<0.01). The protein expression levels of Akt in skin tissue of rats between the two groups were similar immediately after injury (t=0.66, P>0.05). However, the protein expression level of phosphorylated Akt in skin tissue of rats in diabetes group immediately after injury (0.310±0.035) was significantly decreased as compared with that in non-diabetes group (0.790±0.032, t=6.20, P< 0.05). Compared with those in non-diabetes group, the protein expression levels of mTOR and phosphorylated mTOR in skin tissue of rats in diabetes group immediately after injury and the protein expression levels of Akt, phosphorylated Akt, mTOR, and phosphorylated mTOR in wound tissue from PID 1 to 7 were all significantly decreased (with t values from 3.52 to 13.44, P<0.05 or P<0.01). (3) Compared with those in skin tissue immediately after injury, the expressions of phosphorylated Akt and vimentin in wound tissue of rats in the two groups from PID 1 to 7 presented a gradually increased tendency, however, the expressions of these indexes in skin tissue and wound tissue of rats in diabetes group were significantly weaker than those in non-diabetes group. Conclusions: Trauma can stimulate activation of Akt/mTOR signaling pathway, and upregulate the expression of key proteins. The attenuation of this signaling pathway in skin tissue and wound tissue of diabetes mellitus may be the key mechanism for causing impaired healing of wound.