SHOCK最新文献

Abstract: Mice used in biomedical research are typically housed at ambient temperatures (22°C-24°C) below thermoneutrality (26°C-31°C). This chronic cold stress triggers a hypermetabolic response that may limit the utility of mice in modeling hypermetabolism in response to burns. To evaluate the effect of housing temperature on burn-induced hypermetabolism, mice were randomly assigned to receive sham, small, or large scald burns. Mice recovered for 21 days in metabolic phenotyping cages at 24°C or 30°C. Regardless of sex or sham/burn treatment, mice housed at 24°C had greater total energy expenditure ( P < 0.001), which was largely attributable to greater basal energy expenditure when compared to mice housed at 30°C ( P < 0.001). Thermoneutral housing (30°C) altered adipose tissue mass in a sex-dependent manner. Compared to sham and small burn groups, large burns resulted in greater water vapor loss, regardless of housing temperature ( P < 0.01). Compared to sham, large burns resulted in greater basal energy expenditure and total energy expenditure in mice housed at 24°C; however, this hypermetabolic response to large burns was blunted in female mice housed at 30°C, and absent in male mice housed at 30°C. Locomotion was significantly reduced in mice with large burns compared to sham and small burn groups, irrespective of sex or housing temperature ( P < 0.05). Housing at 30°C revealed sexual dimorphism in terms of the impact of burns on body mass and composition, where males with large burns displayed marked cachexia, whereas females did not. Collectively, this study demonstrates a sex-dependent role for housing temperature in influencing energetics and body composition in a rodent model of burn trauma.

Abstract: Background: Acute respiratory distress syndrome (ARDS) is a serious pathological process with high mortality. Ferroptosis is pivotal in sepsis, whose regulatory mechanisms in sepsis-induced ARDS remains unknown. We aimed to determine key ferroptosis-related genes in septic ARDS and investigate therapeutic traditional Chinese medicine. Method: Sepsis-induced ARDS dataset obtained from Gene Expression Omnibus was analyzed to identify ferroptosis-related differentially expressed genes. Enrichment analysis and protein-protein interaction network construction were performed to identify hub genes. Immune cells infiltration was analyzed and competitive endogenous RNA network was constructed. The diagnostic value of hub genes in septic ARDS was analyzed and the occurrence of ferroptosis and the expression of hub genes were detected. Traditional Chinese medicine targeting hub genes was predicted via SymMap database and was verified. Results: Sixteen ferroptosis-related differentially expressed genes were obtained, among which the top four genes ( IL1B , TXN , MAPK3 , HSPB1 ) were selected as hub genes, which may be potential diagnostic markers of septic ARDS. Immunoassay showed that sepsis-induced ARDS and hub genes were closely related to immune cells. The competitive endogenous RNA network showed 26 microRNAs and 38 long noncoding RNA. Ferroptosis occurred and the expressions of IL1B , MAPK3 , and TXN were increased in septic ARDS mice and LPS-challenged human pulmonary alveolar epithelial cells. Sea buckthorn alleviated septic lung injury and affected hub genes expression. Conclusions: Ferroptosis-related genes of IL1B , MAPK 3, and TXN serve as potential diagnostic genes for sepsis-induced ARDS. Sea buckthorn may be therapeutic medication for ARDS. This study provides a new direction for septic ARDS treatment.

Abstract: Background: Acute lung injury (ALI) is a severe condition characterized by a high mortality rate, driven by an uncontrolled inflammatory response. Emerging evidence has underscored the crucial role of the ubiquitin system in ALI. However, because of their vast number, the specific functions of individual ubiquitination regulators remain unclear. Materials and methods: In this study, we established human lung organoids (HLOs) derived from human embryonic stem cells and subjected them to lipopolysaccharide (LPS) treatment to induce an inflammatory response, mimicking ALI. Subsequently, we detected the expression of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin 6, interleukin 18 (IL-18), and interleukin-1β (IL-1β), by quantitative polymerase chain reaction experiments. We also detected changes in the mRNA expression of several USPs before and after HLOs treatment and thus screened for USPs that had significant changes in HLOs after LPS stimulation. After screening for USP, we silenced the USP in HLOs and then subjected them to LPS treatment, and TNF-α, IL-6, IL-18, and IL-1β expressions were detected using quantitative polymerase chain reaction assays. Meanwhile, western blot was used to detect changes in NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) and apoptosis-associated Speck-like protein containing a CARD (ASC) protein level in HLOs. Results: Through screening the expression of 40 ubiquitin-specific proteases (USPs), which are responsible for removing ubiquitination, we identified several USPs that exhibited differential expression in LPS-treated HLOs compared to untreated HLOs. Notably, USP31 emerged as the most significantly upregulated USP, and the knockdown of USP31 markedly attenuated the inflammatory response of HLOs to LPS treatment. Conclusions: USP31 may play a facilitating role in the inflammatory response during ALI.

Abstract: Background: Acute infections and sepsis are a leading cause of death. These patients are primarily encountered at the emergency department (ED), where early assessment for sepsis is necessary to improve outcome. In sepsis, the inflammatory response causes several characteristic pathophysiological changes, including a dysregulated and generalized activation of the endothelium. This study aimed to analyze endothelial markers released to the blood as diagnostic biomarkers for acute infection and sepsis in the ED, as smaller studies have previously shown promising results in other settings. Methods : Serum samples from n = 312 adult patients with suspected acute infections at presentation to the ED were utilized. Patients' courses of disease and outcomes were assessed by clinical adjudication. E-selectin, P-selectin, ICAM-1, and VCAM-1 were measured by ELISAs. The accuracy of each marker for predicting bacterial infection, sepsis, and in-hospital mortality was evaluated. Results : For sepsis, E-selectin and ICAM-1 both showed an area under the receiver operating characteristic (AUROC) of 0.62, lower than procalcitonin with 0.77 (both P < 0.01) and lactate with 0.73 ( P = 0.030 and 0.046, respectively), but similar to CRP with 0.60 ( P = 0.758 and 0.876, respectively). For 28-day in-hospital mortality among patients with infection, ICAM-1 performed best with an AUROC of 0.75. Conclusions : Despite promising results in small studies and specific cohorts, particularly in intensive care units, this large-scale evaluation of four endothelial biomarkers highlights their limited diagnostic utility in a broader inclusion setup design at the earliest possible time point of evaluation.

Abstract: Background : This systematic review and meta-analysis aims to detecting performance of muscular ultrasound for intensive care unit (ICU)-acquired weakness (ICUAW). Methods : We searched PubMed, Web of Science, Embase, Cochrane library, CNKI, VIP, and Wanfang databases for articles published before July 2024. A random-effects model was utilized to derive the summary estimates of sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence interval (CI). Additionally, the sources of heterogeneity were explored by subgroup analysis and meta-regression. Results : This meta-analysis comprised 10 prospective studies involving 561 participants, of whom 241 (42.96%) were diagnosed as ICUAW. Overall, muscular ultrasound exhibited good performance for detecting ICUAW, with the area of summary receiver operating characteristic (SROC) curve of 0.85 (95%CI 0.82-0.88), sensitivity of 0.76 (95%CI 0.70-0.81), specificity of 0.80 (95%CI 0.74-0.84), and DOR of 12.43 (95%CI 7.98-19.38). Upon predefined subgroup analysis, the rectus femoris exhibited significantly superior discriminatory ability in identifying ICUAW than the non-rectus femoris, with higher SROC (0.88 [95%CI 0.85-0.91] vs. 0.76 [95%CI 0.72-0.79], P < 0.01). Moreover, cross-sectional area was more effective than thickness, with higher specificity (0.86 [95%CI 0.80-0.91] vs. 0.74 [95%CI 0.68-0.79], P = 0.02) and SROC (0.89 [95%CI 0.86-0.92] vs. 0.76 [95%CI 0.72-0.80], P < 0.01). Furthermore, integrated analysis of these two indicators revealed that the cross-sectional area of rectus femoris was statistically superior to the thickness of rectus femoris, with higher sensitivity (0.82 [95%CI 0.74-0.87] vs. 0.75 [95%CI 0.65-0.83], P < 0.05) and AUC (0.91 [95%CI 0.88-0.93] vs. 0.80 [95%CI 0.76-0.83], P < 0.01). Conclusions : Muscular ultrasound could be a reliable tool for ICUAW detection. Compared with alternative indices, the cross-sectional area of the rectus femoris exhibits superior detection efficacy and may be considered as a valuable parameter for clinical application.

Abstract: Objective: The combination of catecholamine-resistant vasodilatory shock and acute kidney injury (AKI) is associated with high morbidity and mortality. The role of angiotensin II (ANGII) in this setting is unclear. Methods: We conducted a post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS) 3 trial which assessed the effect of Intravenous ANG II or placebo in patients with refractory vasodilatory shock in 75 intensive care units across nine countries in North America, Australasia, and Europe. We included patients with all stages AKI at initiation of ANG II or placebo and assessed 28-day mortality as primary outcome. We studied mean arterial pressure (MAP) response and days alive and free from renal replacement therapy (RRT) up to day 7 as secondary outcome. Results: Of 321 ATHOS-3 patients, 203 (63%) had AKI at randomization, with stage 3 AKI being dominant (67%). Median age was 63 years and median APACHE II score was 30. By day 28, overall, 118 (58%) of patients had died (53% with ANGII vs. 63% with placebo, hazard ratio = 0.75, 95% CI [0.52-1.08], P = 0.121). Among AKI stage 3 patients, however, ANGII was associated with significantly lower mortality (48% vs. 67%, hazard ratio = 0.57, 95% CI [0.36-0.91], P = 0.024). Additionally, in this subgroup, compared with placebo, patients receiving ANGII were more likely to achieve a MAP response (P < 0.001) and had more days alive and free from RRT (P < 0.001). Conclusions: Compared with placebo, in patients with catecholamine-resistant vasodilatory shock and stage 3 AKI, ANGII is associated with lower 28-day, greater likelihood of MAP response, and more days alive and free from RRT. These findings support the conduct of future ANGII trials in patients with stage 3 AKI.

Abstract: Introduction: Gut ischemia and reperfusion (I/R) injury promotes the release of damage-associated molecular patterns (DAMPs) such as extracellular cold-inducible RNA-binding protein (eCIRP). Gut I/R often leads to acute lung injury (ALI), a major contributor to mortality. Milk fat globule-epidermal growth factor-factor VIII-derived oligopeptide-3 (MOP3) is a novel peptide that attenuates sepsis by opsonizing eCIRP and facilitating its phagocytic clearance. We hypothesized that MOP3 reduces inflammation, mitigates gut and lung injury, and improves survival in gut I/R injury. Methods: Phagocytosis of FITC-labeled eCIRP by intestinal epithelial cells was determined by confocal microscopy, and the cell supernatant was evaluated for cytokine expression by ELISA. Adult C57BL/6 mice underwent 60 min of gut ischemia via superior mesenteric artery occlusion followed by reperfusion. Mice were treated with MOP3 or vehicle via retro-orbital injection at the time of reperfusion. At 4 h post-I/R, blood, gut, and lungs were harvested for further assay. In additional mice, 36-h survival was assessed. Plasma levels of injury and inflammatory markers were measured with colorimetry and ELISA, respectively. Tissue mRNA expression was measured with qPCR. Myeloperoxidase (MPO), TUNEL, histologic injury, and ZO-1 immunohistochemistry assessments were performed. Results: MOP3 significantly increased eCIRP phagocytosis by intestinal epithelial cells ( P < 0.01) and decreased IL-6 release ( P < 0.001). Gut I/R caused elevated plasma eCIRP levels. MOP3 treatment significantly reduced plasma levels of IL-1β ( P < 0.01), IL-6 ( P < 0.05), and lactate dehydrogenase ( P < 0.05) along with a significant decrease in gut ( P < 0.05) and lung ( P < 0.001) injury scores as well as gut cell death ( P < 0.05). Moreover, MOP3 reduced pulmonary levels of chemokines and the granulocyte activation marker MPO after gut I/R. Mechanistically, ZO-1 expression in the gut was decreased following gut I/R injury, whereas MOP3 significantly reversed the decrease in ZO-1 mRNA expression ( P < 0.001). Finally, mice treated with MOP3 exhibited a significant decrease in mortality ( P < 0.05). Conclusions: Treatment with MOP3 effectively mitigates organ injury induced by gut I/R. This beneficial effect is attributed to the facilitation of eCIRP clearance, directing the potential of MOP3 as an innovative therapeutic approach for this critical and often fatal condition.

Abstract: Introduction : Improvements in combat casualty care have increased survival rates, but these patients are at particular risk of developing multiple organ failure (MOF). We investigated the incidence and severity of MOF in a cohort of severe combat casualties. Materials and Methods : This retrospective study included all on-duty French land army war casualties with a severe combat injury requiring intensive care unit admission during 2009-2023. Demographic data, advanced life support interventions, and outcomes were collected. Each organ failure was then analyzed during a 7-day trauma course according to the Sequential Organ Failure Assessment score. Results: Of the 100 patients who met the inclusion criteria, those with persistent MOF at day 4 (MOF group) represented 22% of the total population (median Sequential Organ Failure Assessment score 6.0 [5.3-8.0]). Compared to those without persistent MOF, these patients were more severely injured (median Military Injury Severity Score 38.0 [interquartile range 33.0-56.8] vs. 26.5 [20.0-34.0], P < 0.001) by an explosive mechanism (68.2%) and sustained more traumatic brain injury (40.9% vs. 14.1%, P = 0.013). The MOF group also received significantly more blood units (median 14.0 [8.3-24.8] vs. 6.0 [0.0-12.0], P < 0.001) and massive transfusions (68.2% vs. 32.1%, P = 0.002). Pulmonary and cardiovascular dysfunction were the most frequently observed trauma outcomes. A multivariable logistic regression model showed that MOF persistence at day 4 was significantly associated (odds ratios [95% confidence intervals]) with severe injuries (1.5 [1-2.3], P = 0.042). Conclusion : A high number of severe lesions significantly and independently increased risk of MOF persistence at day 4 after combat-related trauma. These findings are particularly relevant to current and anticipated large-scale combat operations that will challenge battlefield casualty care and evacuation.