A growing body of evidence indicates that the immune system plays a central role in sepsis. By analyzing immune genes, we sought to establish a robust gene signature and develop a nomogram that could predict mortality in patients with sepsis. Herein, data were extracted from the Gene Expression Omnibus and Biological Information Database of Sepsis (BIDOS) databases. We enrolled 479 participants with complete survival data using the GSE65682 dataset, and grouped them randomly into training (n = 240) and internal validation (n = 239) sets based on a 1:1 proportion. GSE95233 was set as the external validation dataset (n=51). We validated the expression and prognostic value of the immune genes using the BIDOS database. We established a prognostic immune genes signature (including ADRB2, CTSG, CX3CR1, CXCR6, IL4R, LTB, and TMSB10) via LASSO and Cox regression analyses in the training set. Based on the training and validation sets, the Receiver Operating Characteristic curves and Kaplan-Meier analysis revealed that the immune risk signature has good predictive power in predicting sepsis mortality risk. The external validation cases also showed that mortality rates in the high-risk group were higher than those in the low-risk group. Subsequently, a nomogram integrating the combined immune risk score and other clinical features was developed. Finally, a web-based calculator was built to facilitate a convenient clinical application of the nomogram. In summary, the signature based on the immune gene holds potential as a novel prognostic predictor for sepsis.

Background: Cerebral ischemic stroke is a serious condition with high incidence, mortality, and associated disability. Currently, effective therapeutic options are available for ischemic stroke are limited. Accumulating evidence indicates that sodium Danshensu, mono sodium compound derived from Salvia miltiorrhiza, plays protective roles in ischemic stroke. However, the underlying protective mechanism of sodium Danshensu in cerebral ischemic stroke remains unknown.Methods: In the current study, we explored the role and mechanism of sodium Danshensu on astrocytes exposed to oxygen-glucose deprivation/reoxygenation (OGD/R), which mimics the process of ischemiareperfusion. The impact of sodium Danshensu on cell viability and apoptosis after OGD/R were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-dophenyl tetrazolium bromide (MTT) assay and flow cytometry.Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot were used to detect the expression of target messenger RNA (mRNA) and proteins associated with apoptosis and autophagy. The release of lactate dehydrogenase (LDH) was determined, and the production of proinflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA) kits.Results: It was found that sodium Danshensu could significantly increase cell viability and decrease LDH release and apoptosis. Besides, it inhibited the production of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. Sodium Danshensu also dose-dependently decreased protein and mRNA levels of nucleotide binding oligomerization NOD-like receptor pyrin domain containing 3 (NLRP3) and high mobility group box 1 (HMGB1), which play a crucial role in promoting ischemic stroke-induced cell injury. Moreover, sodium Danshensu dose-dependently upregulated Beclin 1 expression, downregulated P62 protein expression, and further increased LC3B-II/LC3B-I ratio through inducing autophagy in astrocytes. Additionally, we noticed that sodium Danshensu dose-dependently increased tuberous sclerosis complex-2 (TSC2) protein expression, while significantly reduced the levels of mammalian target of rapamycin (mTOR) in the presence of OGD/R insult.Conclusions: These findings suggest that sodium Danshensu protects against OGD/R-induced injury by modulating the NLRP3 inflammasome and TSC2/mTOR pathways.

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