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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Objective: To uncover critical active proteins influencing sepsis outcomes through multiomics analysis. Methods: This study collected peripheral blood from sepsis patients (NS = 26, SV = 27) and controls (Con = 16). Cellular heterogeneity was assessed using scRNA-seq. ⋯ Four proteins (SPI1, MEF2A, CBX3, UBTF) with prognostic significance were discovered and mapped onto the cellular landscape. Gene set variation analysis enrichment analysis revealed that the NS group exhibited significant alterations in pathways related to cellular apoptosis and inflammatory responses, while the SV group displayed increased activity in DNA repair and cellular survival pathways. Conclusion: The study's findings advance the understanding of sepsis pathophysiology by linking differentially active proteins to patient prognosis, paving the way for targeted therapeutic strategies.
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Observational Study
A nomogram based on the value of the dynamic evolution of systemic immune inflammatory index in the evaluation of severe heatstroke.
Background : Severe heatstroke patients have a poor prognosis. There are few descriptions of the inflammatory response to heatstroke in clinical studies. Systemic immune-inflammation index (SII) is a new index to reflect the inflammatory state of disease. ⋯ Patients with SII 72 > 1,000 had poor clinical prognosis. Conclusions : Compared to SII results from the first and second days, third-day results more meaningfully predict poor heatstroke prognosis. SII 72 may be a good indicator and, when combined with SOFA, offers enhanced predictive value.
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Background : Previous preclinical studies have demonstrated a pathobiome after traumatic injury; however, the impact of postinjury sepsis on gut epithelial permeability and bacterial translocation remains unknown. We hypothesized that polytrauma with postinjury pneumonia would result in impaired gut permeability leading to specific blood microbiome arrays. Methods : Male and proestrus female Sprague-Dawley rats were subjected to either polytrauma (PT), PT plus 2-hours daily chronic restraint stress (PT/CS), PT with postinjury day 1 inoculation with pseudomonas pneumonia (PT + PNA), PT/CS + PNA, or naive controls. ⋯ Females PT/CS + PNA had a significant abundance of Staphylococcus at day 2 and Streptococcus at day 7 in the blood biome compared to male counterparts ( P < 0.05). Conclusion : Multicompartmental trauma with postinjury pneumonia results in increased intestinal permeability and bacteremia with a unique blood biome, with sexual dimorphisms evident in the blood biome composition. These findings suggest that postinjury sepsis has clinical significance and could influence outcomes after severe trauma and critical illness.
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This study aimed to investigate the protective effect of pentoxifylline (PTX) on vascular endothelial dysfunction in uremia. The human aortic endothelial cells (HAECs) required for the experiments were all obtained from the National Collection of Authenticated Cell Cultures (Salisbury, UK). The permeability of HAECs was assessed. ⋯ The expression of NLRP3 (0.810 ± 0.032, P = 0.02) and caspase-1 (0.580 ± 0.041, P = 0.03) was increased, whereas the expression of ZO-1 (0.255 ± 0.038, P = 0.03) and VE-cadherin (0.0546 ± 0.053, P = 0.02) was decreased in the uremia group; compared with the healthy volunteer group, treated with PTX (NLRP3, 0.298 ± 0.042, P = 0.03; caspase-1, 0.310 ± 0.021, P = 0.03; ZO-1, 0.412 ± 0.028, P = 0.02; VE-cadherin, 0.150 ± 0.034, P = 0.02) and MCC950 (NLRP3, 0.432 ± 0.022, P = 0.03; caspase-1, 0.067 ± 0.031, P > 0.05; ZO-1, 0.457 ± 0.026, P = 0.03; VE-cadherin, 0.286 ± 0.017, P = 0.03) these lessened this trend. Pentoxifylline promoted the HAEC permeability mediated by uremic toxins (1.507 ± 0.012, P = 0.02). In conclusion, PTX enhances the release of HMGB1, which is dependent on NLRP3 activation, and consequently exerts positive effects on interconnecting proteins, ultimately leading to an improvement in vascular permeability.