Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Purpose : The objective of this study is to establish a nomogram that correlates optimized Acute Physiology and Chronic Health Evaluation II (APACHE II) score with sepsis-related indicators, aiming to provide a robust model for early prediction of sepsis prognosis in clinical practice and serve as a valuable reference for improved diagnosis and treatment strategies. Methods : This retrospective study extracted sepsis patients meeting the inclusion criteria from the MIMIC-IV database to form the training group. An optimized APACHE II score integrated with relevant indicators was developed using a nomogram for predicting the prognosis of sepsis patients. ⋯ Calibration curves and decision curve analyses also confirmed its good predictive ability, surpassing the APACHE II score and Sequential Organ Failure Assessment score in identifying high-risk patients. Conclusions : The nomogram was established in this study using the MIMIC-IV database and validated with external data, demonstrating its robust discriminability, calibration, and clinical practicability for predicting 28-day mortality in sepsis patients. These findings aim to provide substantial support for clinicians' decision making.
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Introduction: Previous studies have manifested that those sedatives acting on γ-aminobutyric acid A (GABAa) receptor could produce effective brain protection against regional and global ischemic stimulation. The present study was designed to investigate the effect of a novel GABAa receptor agonist, remimazolam postconditioning (RP) on cerebral outcome after global ischemic stimulation induced by cardiac arrest and resuscitation in swine. Methods: A total of 24 swine were used in this study, in which the animals were randomly divided into the following three groups: sham group (n = 6), cardiopulmonary resuscitation (CPR) group (n = 9), and CPR + RP group (n = 9). ⋯ At 24 h after resuscitation, tissue inflammation, oxidative stress, and cell apoptosis and necroptosis were significantly increased in the CPR and CPR + RP groups when compared with the sham group. Nevertheless, the severity of pathologic damage mentioned previously were significantly milder in those swine treated with the remimazolam when compared with the CPR group. Conclusions: In a swine model of cardiac arrest and resuscitation, the remimazolam administered after resuscitation significantly improved the markers of postresuscitation cerebral injury and therefore protected the brain against global ischemic stimulation.
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Background : Sepsis-induced cardiomyopathy ( SIC ) is a common complication of sepsis with high morbidity and mortality but lacks specific therapy. The purpose of this study was to investigate the role of circularRNA_0003907 (circ_0003907) in myocardium injury induced by sepsis. Methods: In this experiment, human AC16 cells were treated with lipopolysaccharide (LPS) to induce an in vitro cardiomyocyte injury model. ⋯ In mechanism, circ_0003907 acted as a sponge for miR-944 to increase MYD88 expression. Meanwhile, the absence of circ_0003907 induced miR-944 expression and suppressed MYD88/NLRP3/NF-κB levels. Conclusion: Circ_0003907 sponged miR-944 to aggravate LPS-induced AC16 cell dysfunction via activating the MYD88/NLRP3/NF-κB axis during sepsis, which might provide a new direction for the treatment of SIC .
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Background: Sepsis is a type of life-threatening organ dysfunction that is caused by a dysregulated host response to infection. The lung is the most vulnerable target organ under septic conditions. Pulmonary microvascular endothelial cells (PMVECs) play a critical role in acute lung injury (ALI) caused by severe sepsis. ⋯ Treatment with the sarco/endoplasmic reticulum Ca 2+ adenosine triphosphatase inhibitor, thapsigargin, resulted in a significant reduction in cell viability as well as a reduction in the expression of junctional proteins, including vascular endothelial-cadherin and occludin. Treatment with the store-operated Ca 2+ entry inhibitor, YM-58483 (BTP2), increased the cell viability and expression of junctional proteins. Conclusions: The present study suggested that H 2 treatment alleviates LPS-induced PMVEC dysfunction by inhibiting store-operated Ca 2+ entry mediated by STIM1 and Orai1 in vitro and in vivo .
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Cardiac fibrosis, characterized by excessive collagen accumulation in heart tissues, poses a significant clinical challenge in various heart diseases and complications. Although salvianolic acid A (Sal A) from Danshen ( Salvia miltiorrhiza ) has shown promise in the treatment of ischemic heart disease, myocardial infarction, and atherosclerosis, its effects on cardiac fibrosis remain unexplored. Our study investigated the efficacy of Sal A in reducing cardiac fibrosis and elucidated its underlying molecular mechanisms. ⋯ RNA sequencing revealed that Sal A counteracted Ang II-induced upregulation of Txnip, and subsequent experiments indicated that it acts through the inflammasome and ROS pathways. These findings establish the antifibrotic effects of Sal A, notably attenuated by Txnip overexpression, and highlight its significant role in modulating inflammation and oxidative stress pathways. This underscores the importance of further research on Sal A and similar compounds, especially regarding their effects on inflammation and oxidative stress, which are key factors in various cardiovascular diseases.