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 : Continuous kidney replacement therapy (CKRT) is a crucial intervention for hemodynamically unstable patients with acute kidney injury (AKI). Despite the recommendations to offer a CKRT dose of 20 to 25 mL/kg/h, the optimal CKRT dose remains uncertain, especially whether low-dose CKRT is associated with poor outcomes. This study investigated the association between low CKRT dosage and 90-day mortality using a marginal structural model (MSM). ⋯ Additionally, there were no significant associations between the delivered CKRT dose and 90-day mortality within the range of 5 to 40 mL/kg/h. Conclusion : This study highlights the impact of methodological approaches on the association between CKRT dose and mortality and that with personalized adjustments, there may not be a lower limit of the unsafe CKRT dose. However, lower CKRT doses were initially associated with higher mortality, and adjusting for time-dependent variables nullified this association.
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Background: Ubiquitination and deubiquitination are involved in the progression of human diseases, including acute pneumonia. In this study, we aimed to explore the functions of ubiquitin-specific peptidase 9X-linked (USP9X) in lipopolysaccharide (LPS)-treated WI-38 cells. Methods: WI-38 cells were treated with LPS to induce the cellular damage and inflammation. 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and 5-ethynyl-2'-deoxyuridine (EdU) assay were performed to examine the proliferation of LPS-treated WI-38 cells. ⋯ USP9X knockdown restored the effects of LPS on WI-38 cell proliferation, apoptosis, inflammation, and oxidative stress, but these effects of USP9X knockdown were further abolished by TBL1XR1 overexpression. In addition, USP9X promoted the NF-κB signaling pathway by the deubiquitination of TBL1XR1. Conclusion: USP9X promoted the apoptosis, inflammation, and oxidative stress of LPS-stimulated WI-38 cells through the deubiquitination of TBL1XR1.
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Background: Acute lung injury (ALI) is a severe complication of sepsis, characterized by inflammation, edema, and injury to alveolar cells, leading to high mortality rates. Septic ALI is a complex disease involving multiple factors and signaling pathways. STEAP family member 1 (STEAP1) has been reported to be upregulated in a sepsis-induced ALI model. ⋯ Moreover, METTL14 silencing attenuated LPS-induced effects by decreasing STEAP1 expression in HPMECs, and STEAP1 silencing ameliorated cecal ligation and puncture-induced lung injury of mice. Conclusion: METTL14/IGF2BP2-mediated m6A modification of STEAP1 aggravated ALI induced by sepsis. These findings suggest potential therapeutic targets for the treatment of this disease.
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Objective : To evaluate if mechanical left ventricular unloading could reduce mortality in patients with cardiogenic shock undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO). Methods : We searched MEDLINE, Embase, and the Cochrane Library for randomized controlled trials and propensity score-matched studies published until December 20, 2023. The primary outcome was mortality at the longest follow-up. ⋯ Mechanical left ventricular unloading was significantly associated with reduced mortality at the longest follow-up (RR, 0.89; 95% CI, 0.84-0.94; P = 0.0001; moderate certainty of evidence), which was confirmed in studies using intra-aortic balloon pump. Benefits of mechanical unloading were also observed in terms of successful VA-ECMO weaning (RR, 1.15; 95% CI, 1.02-1.29; P = 0.02; low certainty of evidence) and favorable neurological outcome (two studies; RR, 2.45; 95% CI, 1.62-3.69; P < 0.0001; low certainty of evidence), although we observed an increased incidence of major bleeding (RR, 1.27; 95% CI, 1.02-1.59; P = 0.03; low certainty of evidence) and hemolysis (RR, 1.49; 95% CI, 1.10-2.02; P = 0.01; moderate certainty of evidence). Conclusions : Among adult patients with cardiogenic shock treated with VA-ECMO, mechanical left ventricular unloading was associated with reduced mortality, which was confirmed in studies using intra-aortic balloon pump as an unloading device.
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Objective: The mechanisms underlying the increased severity of hypertriglyceridemia acute pancreatitis (HTG-AP) remain poorly understood. Fibrinogen-like protein 2 (FGL2) has been identified as a regulator of macrophage activity, mediating immune suppression. This study aims to examine the role of FGL2 in the susceptibility to severe conditions of HTG-AP. ⋯ In the HTG-AP group, there was a marked increase in CD68 and iNOS expressions, coupled with a reduction in CD163 expression. Conclusion: FGL2 knockout in HTG and HTG-AP mice resulted in increased inflammatory responses and a significant imbalance in M2 macrophages. These findings suggest that FGL2 plays a crucial role in mitigating the aggravation of HTG on the severity of HTG-AP by modulating macrophage activity.