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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Background : This study aims to determine the impact and mechanism of miR-21-3p on intestinal injury and intestinal glycocalyx during fluid resuscitation in traumatic hemorrhagic shock (THS), and the different impacts of sodium lactate Ringer's solution (LRS) and sodium bicarbonate Ringer's solution (BRS) for resuscitation on intestinal damage. Methods : A rat model of THS was induced by hemorrhage from the left femur fracture. The pathological changes of intestinal tissues and glycocalyx structure were observed by hematoxylin-eosin staining and transmission electron microscope. ⋯ The adverse effect of LRS was more serious than BRS. MiR-21-3p overexpression deteriorated the injury of intestinal tissues and intestinal glycocalyx; increased the expression of SDC-1, HPA, β-catenin, MMP2, and MMP9 while decreasing E-cad expression; and activated the PI3K/Akt/NF-κB signaling pathway in BRS-resuscitated THS rats. Conclusion : MiR-21-3p aggravated intestinal tissue injury and intestinal glycocalyx damage through activating PI3K/Akt/NF-κB signaling pathway in rats with THS resuscitated with BRS.
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Intestinal ischemia-reperfusion injury (IIRI) is a serious disease with high morbidity and mortality. This study aims to investigate the potential regulatory mechanisms involving protein arginine methyltransferase 6 (PRMT6), Forkhead box O3a (FoxO3a), and Parkin in IIRI and elucidate their roles in mediating cell apoptosis. The IIRI animal model was established and confirmed using hematoxylin and eosin staining. ⋯ Notably, the levels of PRMT6, FoxO3a, and Parkin were decreased in IIRI mouse intestinal tissue. Knocking out PRMT6 causes a significant decrease in the lifespan of mice. Altogether, our results demonstrated that PRMT6 upregulated the expression of Parkin by regulating FoxO3a methylation level, attenuating the apoptosis induced by IIRI.
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Observational Study
Immunosuppression correlates with the deterioration of sepsis-induced disseminated intravascular coagulation.
Background: The dysregulated host responses play a crucial role in the pathophysiology process of sepsis-induced disseminated intravascular coagulation (DIC). The study aimed to characterize the dynamic alternation of immune-related biomarkers and their relationship with the progression of DIC during sepsis. Methods: A prospective, observational study was conducted in a tertiary care academic hospital. ⋯ The patients with overt DIC displayed pronounced immune disorders from D1 to D7 upon sepsis, which was characterized by the decreased percentage of monocyte HLA-DR (mHLA-DR), increased percentage of regulatory T cells, the levels of procalcitonin, neutrophil CD64 index, and systemic inflammatory cytokines relative to nonovert DIC or non-DIC patients. In multivariate analysis, the combination of anti-inflammatory cytokine IL-10 and mHLA-DR at D1 upon enrollment had a superior predictive value for predicting DIC deterioration in sepsis (area under the curve = 0.87, P < 0.0001). Conclusion: These data illustrate that immunosuppression can crosstalk with coagulation disorder during sepsis and present an additional evaluation tool to predict DIC deterioration.
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Background: Critical care management of shock is a labor-intensive process. Precision Automated Critical Care Management (PACC-MAN) is an automated closed-loop system incorporating physiologic and hemodynamic inputs to deliver interventions while avoiding excessive fluid or vasopressor administration. To understand PACC-MAN efficacy, we compared PACC-MAN to provider-directed management (PDM). ⋯ Urine outputs were similar between PACC-MAN and PDM (14.0 mL/kg vs. 21.5 mL/kg, P = 0.13). Conclusion : Automated resuscitation achieves equivalent resuscitation outcomes to direct human intervention in this shock model. This study provides the first translational experience with the PACC-MAN system versus PDM.