Effect of tocilizumab plus corticosteroid on clinical outcome in patients hospitalized with severe fever with thrombocytopenia syndrome: A randomized clinical trial.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with high fatality rates. The blockade of pro-inflammatory cytokines presents a promising therapeutic strategy. METHODS: We conducted a randomized clinical trial at the 154th hospital, Xinyang, Henan Province. Eligible patients with severe SFTS disease were randomly assigned in a 1:2 ratio to receive either a single intravenous infusion of tocilizumab plus usual care; or usual care only. The primary outcome was the clinical status of death/survival at day 14, while secondary outcomes included improvement from baseline in liver and kidney damage and time required for hospital discharge. The efficacy of tocilizumab plus corticosteroid was compared to those receiving corticosteroid alone. The trial is registered with the Chinese Clinical Trial Registry website (ChiCTR2300076317). RESULTS: 63 eligible patients were assigned to the tocilizumab group and 126 to the control group. The addition of tocilizumab to usual care was associated with a reduced death rate (9.5%) compared to those received only usual care (23.0%), with an adjusted hazard ratio (aHR) of 0.37 (95% confidence interval [CI], 0.15 to 0.91, P = 0.029). Combination therapy of tocilizumab and corticosteroids was associated with a significantly reduced fatality (aHR, 0.21; 95% CI, 0.08 to 0.56; P = 0.002) compared to those receiving corticosteroids alone. CONCLUSIONS: A significant benefit of reducing fatality in severe SFTS patients was observed by using tocilizumab. A combined therapy of tocilizumab plus corticosteroids was recommended for the therapy of severe SFTS.

A novel lncRNA-miRNA-mRNA competing endogenous RNA regulatory network in lung adenocarcinoma and kidney renal papillary cell carcinoma.

BACKGROUND: GPRIN1 may be a novel tumor regulator, but its role and mechanism in tumors are still unclear. METHODS: First, a pan-cancer correlation analysis was conducted on the expression and prognosis of GPRIN1 based on the data downloaded from The Cancer Genome Atlas (TCGA) database. Second, the Starbase database was used to predict the upstream miRNAs and lncRNAs of GPRIN1, and the expression analysis, survival analysis, and correlation analysis were performed to screen the microRNA (miRNAs)/long non-coding RNAs (lncRNAs) that had a correlation with kidney renal papillary cell carcinoma (KIRP) or lung adenocarcinoma (LUAD). Third, the CIBERSORT algorithm was employed to calculate the proportion of various types of immune cells, and then the R packages were used for evaluating the relation between GPRIN1 expression and tumor immune cell infiltration as well as between GPRIN1 and the immune cell biomarker. Finally, the correlation analysis was made on GPRIN1 and immune checkpoints (CD274, CTLA4, and PDCD1). RESULTS: The pan-cancer analysis suggested that GPRIN1 was up-expressed in KIRP and LUAD, and it correlated with poor prognosis. LINC00894/MMP25-AS1/SNHG1/LINC02298/MIR193BHG-miR-140-3p was likely to be the most promising upstream regulation pathway of GPRIN1. Upexpression of LINC00894/MMP25-AS1/SNHG1/LINC02298/MIR193BHG and downexpression of miR-140-3p were found relevant with poor outcomes of KIRP and LUAD. GPRIN1 expression was significantly correlated with tumor immune cell infiltration, immune cell biomarkers, and immune checkpoints. CONCLUSIONS: The competitive endogenous (ceRNA) of miR-140-3p-GPRIN1 axis and its upstream lncRNAs are closely related to KIRP and LUAD, and might affect the prognosis and therapeutic effect of KIRP and LUAD.