Effect of an Herbal-Based Injection on 28-Day Mortality in Patients With Sepsis: The EXIT-SEP Randomized Clinical Trial.

Importance: Previous research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis. Objective: To determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis. Design, Setting, and Participants: The Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022. Interventions: The patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days. Main Outcomes and Measures: The primary outcome was 28-day mortality. Results: Among the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group. Conclusions and Relevance: In this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03238742.

Characterization of lncRNA-Based ceRNA Network and Potential Prognostic Hub Genes for Sepsis.

Objective: Sepsis is one of the most common reasons for hospitalization and in-hospital mortality each year. Noncoding RNAs have been reported not only as diagnostic and prognostic indicators but also as therapeutic targets of sepsis. Herein, we used an integrative computational approach to identify miRNA-mediated ceRNA crosstalk between lncRNAs and genes in sepsis based on the "ceRNA hypothesis" and investigated prognostic roles of hub genes in sepsis. Methods: Two good-quality gene expression datasets with more than 10 patient samples, GSE89376 and GSE95233, were employed to obtain differentially expressed lncRNAs (DElncRNAs) and genes (DEGs) in sepsis. The DElncRNA-miRNA-DEG regulatory network was constructed using a combination of DElncRNA-miRNA pairs and miRNA-DEmRNA pairs. The protein-protein interaction (PPI) network was constructed by mapping DEGs into the STRING database to identify hub genes in sepsis. The clinical and prognostic significance of hub genes was validated in 89 patients with post-traumatic sepsis. Results: The integrative computational approach identified 311 DEGs and 19 DElncRNAs between septic patients and healthy volunteers. Results yielded 122 downDElncRNA-miRNA-downDEG networks based on two lncRNAs, HCP5, and HOTAIRM1, and 36 upDElncRNA-miRNA-upDEG network based on BASP1-AS1. The PPI network identified serum/glucocorticoid regulated kinase 1 (SGK1), arrestin beta 1 (ARRB1), and G protein-coupled receptor 183 (GPR183) as located at the core of the network, and three of them were downregulated in sepsis. SGK1, ARRB1, and GPR183 were all involved in lncRNA HCP5-based ceRNA network. The quantitative real-time PCR revealed that the patients with post-traumatic sepsis exhibited reduced relative mRNA levels of SGK1, ARRB1, and GPR183 compared to the patients without sepsis. The nonsurvivor group, according to the 28-day mortality, showed lower relative mRNA levels of SGK1, ARRB1, and GPR183 than the survivor group. We also demonstrated reduced mRNA levels of SGK1, ARRB1, and GPR183 were associated with sepsis-related death after trauma. Conclusion: Our integrative analysis and clinical validation suggest lncRNA HCP5-based ceRNA networks with SGK1, ARRB1, and GPR183 involved were associated with the occurrence and progression of sepsis.

Doxorubicin-loaded mesoporous silica nanoparticle composite nanofibers for long-term adjustments of tumor apoptosis.

There is a high local recurrence (LR) rate in breast-conserving therapy (BCT) and enhancement of the local treatment is promising as a way to improve this. Thus we propose a drug delivery system using doxorubicin (DOX)-loaded mesoporous silica nanoparticle composite nanofibers which can release anti-tumor drugs in two phases-burst release in the early stage and sustained release at a later stage-to reduce the LR of BCT. In the present study, we designed a novel composite nanofibrous scaffold to realize the efficient release of drugs by loading both DOX and DOX-loaded mesoporous silica nanoparticles into an electrospun PLLA nanofibrous scaffold. In vitro results demonstrated that this kind of nanomaterial can release DOX in two phases, and the results of in vivo experiments showed that this hybrid nanomaterial significantly inhibited the tumor growth in a solid tumor model. Histopathological examination demonstrated that the apoptosis of tumor cells in the treated group over a 10 week period was significant. The anti-cancer effects were also accompanied with decreased expression of Bcl-2 and TNF-α, along with up-regulation of Bax, Fas and the activation of caspase-3 levels. The present study illustrates that the mesoporous silica nanoparticle composite nanofibrous scaffold could have anti-tumor properties and could be further developed as adjuvant therapeutic protocols for the treatment of cancer.