SHOCK最新文献

Background: Sepsis is a clinical syndrome characterized by dysregulated inflammatory and immune responses, leading to multiple organ dysfunction. Neutrophil extracellular traps (NETs) have attracted increasing attention for their role in this process. This study was then performed to conduct a bibliometric analysis to explore research progress on the involvement of NETs in the pathophysiology of sepsis.

Methods: This bibliometric analysis was conducted using CiteSpace and VOSviewer based on literature retrieved from the Web of Science Core Collection WoSCC database from 2004-2025.

Results: A total of 809 publications from 2,804 institutions across 224 countries/regions, published in 315 journals, were included. The United States, China, and Germany were the top three contributing countries, with Harvard University leading among institutions. Herrmann Martin was the most prolific author, while Volker Brinkmann's work received the highest co-citation frequency. Frontiers in Immunology and Blood ranked first in publication volume and co-citation frequency, respectively. Co-citation and clustering analyses delineated a thematic evolution from early studies on immune response and systemic infection toward current emphases on organ injury, coagulation dysfunction, and clinically oriented translational therapeutic research in NETs-related sepsis. Keyword co-occurrence analysis highlighted increasing interest in mechanistic topics such as GSDMD and immunothrombosis, while citation burst analysis pointed to growing attention on lung injury and heparin in therapeutic and translational contexts.

Conclusions: This study summarizes the developmental trajectory, current landscape, and future directions of research on NETs in sepsis, and highlights the growing emphasis on understanding the immunopathological mechanisms of NET-mediated injury as well as the translational studies derived from these mechanistic insights.

Preclinical models using animals are crucial for medical advancements despite their limitations and criticisms. Critical illnesses like sepsis, trauma, and burns remain huge causes of morbidity and mortality despite medical advances, and human studies may not always be feasible. In this part 1 of 2 reviews about animal models for critical illness, we discuss sepsis and the considerations one should take to optimize the rodent sepsis model. There are multiple models of sepsis used, each with advantages and disadvantages and they can be modified to reflect how patients are treated in the hospital, including intensive care unit care. Patient factors like age, sex, and comorbidities are important considerations given the different responses to sepsis. Aspects of sepsis that our patients encounter including muscle and neurocognitive dysfunction can be modeled to try and improve those aspects of outcomes. Choosing the right models for the question one is asking and optimizing that model is key to recapitulate the human condition to make animal models more translatable to humans. In other words, we suggest that, in lieu of abandoning animal models of sepsis, we seek to enhance translatability to the human condition.

Traumatic brain injury (TBI) is a significant cause of death and disability, affecting nearly 300,000 Americans annually. Beyond the immediate physical damage, TBI induces chronic neuroinflammation and long-term neurodegeneration, leading to various neurologic and psychiatric disorders. This review examines the cerebrovascular unit (CVU), particularly the cerebral endothelial cells, and their critical role in the aftermath of TBI. Following TBI, the CVU undergoes functional changes to counteract inflammation, repair endothelial damage, and promote angiogenesis. However, dysregulation of these protective mechanisms can lead to chronic neuroinflammation, increased cerebrovascular permeability, and systemic endothelial dysfunction. The review explores the molecular and cellular responses of the CVU following TBI, highlighting the roles of inflammatory cytokines, oxidative stress, and various endothelial transport mechanisms. Moreover, TBI-related endothelial dysfunction may extend beyond the brain, potentially contributing to systemic complications such as acute respiratory distress syndrome (ARDS) and multisystem organ failure. Despite the gravity of these conditions, clinical breakthroughs remain limited. This review underscores the necessity for targeted therapeutic strategies to mitigate endothelial dysfunction and improve long-term outcomes for TBI patients. Future research is essential to elucidate the precise mechanisms driving CVU dysfunction and to develop interventions that can alleviate the chronic effects of TBI.

Nearly half of the burn patients in the United States are under the influence of alcohol at the time of injury and alcohol intoxication is associated with poor clinical outcomes. Ethanol has been shown to worsen burn-induced intestinal dysfunction and inflammation, facilitating bacterial translocation from the intestine to the mesenteric lymph nodes and systemic circulation. Regenerating islet-derived protein 3-gamma (REG3G), an antimicrobial peptide crucial for maintaining intestinal homeostasis, protects mice from ethanol-induced bacterial translocation. In this study, we utilized a murine model to determine whether REG3G protects against the combined effects of acute ethanol exposure and burn injury. Mice with intestinal epithelial cell-specific overexpression of REG3G (Reg3g-Tg) were evaluated for gut barrier function, intestinal and hepatic inflammatory cytokines, and antimicrobial peptide expression after ethanol and burn injury. Additionally, we performed 16S rRNA gene sequencing of fecal microbiota. Our results demonstrate that ethanol exposure before burn injury downregulates the antimicrobial peptide REG3G in the ileum, when compared to burn alone. Intestine-specific overexpression of REG3G reversed several gastrointestinal effects of the combined injury, reducing intestinal inflammation and preventing bacterial translocation to the lymph nodes. Moreover, Reg3g-Tg mice exhibited reduced liver inflammation after combined injury, suggesting that improving intestinal function can also influence extra-intestinal organs. These findings highlight the therapeutic potential of REG3G in mitigating the effects of burn injury and alcohol intoxication.

Background: Sepsis-induced liver injury affects about 34.7% of patients and correlates with prognosis. Although vitamin A (VA) and retinol-binding protein 4 (RBP4) are reduced in sepsis, The protective role of VA remains unknown. This study aimed to explore the effects of VA and mechanisms in septic liver injury.

Methods: Cecal ligation puncture (CLP) was performed in male C57BL/6 mice. After 24h, retinol (ROL, 0.01, 0.1, 1 mg/kg), RBP4 (0.5 mg/kg), or their combinations were administered. Liver/serum samples collected 24h later assessed injury (histopathology, function) and RIG-I/RIPK1/RIPK3/MLKL expression via IHC, WB, and RT-qPCR. In LPS-stimulated AML-12 cells, ROL, RBP4, ROL+RBP4, or retinoic acid (RA) effects were evaluated.

Results: CLP mice showed decreased serum ROL at 12h (lowest at 24h), while RBP4 transiently rose at 3h before declining (lowest at 24h). ROL (1 mg/kg) + RBP4 significantly improved survival, reduced liver injury (low Knodell scores), and suppressed RIG-I/TNF-α/RIPK1-RIPK3-MLKL necroptosis. LPS reduced RBP4 in AML-12 cells (p<0.001); ROL+RBP4 and RA alleviated damage via inhibiting necroptosis.

Conclusion: VA may exert hepatoprotection by suppressing RIG-I, reducing TNF-α, and inhibiting RIPK1/RIPK3/MLKL-mediated necroptosis.

Background: Advanced age significantly increases postoperative complication risk, including neurological dysfunction. While the liver plays a critical role in surgical recovery, age-related changes in hepatic function remain inadequately studied in perioperative risk assessment. Methylation-Controlled J protein (MCJ), an endogenous negative regulator of mitochondrial function, represents a promising therapeutic target due to its role in exacerbating oxidative stress and compromising metabolic resilience in aging.

Methods: Young (4-5 months) and aged (24 months), male and female C57BL/6J mice underwent 60-minute laparotomy surgery or sham procedure. Treatment groups received hepatocyte-targeted GalNAc-siMCJ (10 mg/kg, subcutaneous) 72 hours pre-surgery based on established knockdown kinetics. Subclinical liver injury (plasma/tissue cytokeratin-18 (CK18), microRNA-122 (miR-122)), metabolic dysfunction (kynurenine pathway metabolites), blood-brain barrier integrity (cerebrospinal fluid (CSF)/plasma albumin ratio, calcium-binding protein S100B), neuroinflammation (glial fibrillary acidic protein (GFAP), ionized calcium binding adaptor molecule 1 (Iba1)), and cognitive function (open field, novel object recognition) were assessed 48 hours post-surgery.

Results: Despite normal transaminases (alanine aminotransferase (ALT) <46 IU/L, aspartate aminotransferase (AST) <69 IU/L), livers from aged mice exhibited significant subclinical injury after surgery, with elevated CK18 and miR-122 (p < 0.05 vs. aged-sham). This resulted in increased hepatic kynurenine and quinolinic acid (p < 0.05), blood-brain barrier disruption (increased S100B plasma levels and CSF/plasma albumin ratio), neuroinflammation (elevated Iba1 immunoreactivity in hippocampus), and cognitive impairment. Hepatic MCJ silencing prevented these alterations in aged mice (p < 0.05 vs. aged vehicle), without affecting young mice beyond reducing inflammatory markers.

Conclusions: Targeted hepatic MCJ inhibition mitigates subclinical liver injury, dysregulated kynurenine metabolism, and subsequent neuroinflammation in aged mice after surgery. This liver-brain axis modulation represents a potential therapeutic strategy to prevent perioperative neurological complications in vulnerable older surgical patients.

Background: Burn injury produces a complex biological response across multiple organ and biological systems. Nonetheless current understanding regarding the neurologic response to burn injury is limited. Research suggests that disruption of the blood-brain barrier (BBB) may play a role in central nervous system (CNS) damage following burn trauma. As such, the purpose of this study was to investigate systemic circulating biomarkers, frequently associated with neuronal injury, to gain an understanding of their relationship to burn injury severity.

Methods: Blood from fifty-six patients admitted to the burn intensive care units was taken within 24 hours and analyzed for four CNS-related biomarkers in plasma (i.e., ubiquitin C-terminal hydrolase L1 [UCH-L1], tau protein, glial fibrillary acidic protein [GFAP], and neurofilament light [NfL]). Clinical information regarding demographics, burn severity, and health outcomes were also obtained.

Results: We observed increased burn severity, as measured by total burn surface area (TBSA), was significantly associated with increased UCH-L1, NfL, and tau. GFAP was not associated with burn severity. In a predictive model of days spent in the hospital after injury, accuracy of the four CNS-related biomarkers was only improved by 1% when TBSA was included (i.e., 38.3% accuracy with only biomarkers vs. 39.4% accuracy with biomarkers and TBSA).

Conclusion: Overall, findings from this novel study highlight an association between burn injury severity and CNS-related biomarkers, thereby providing a foundation for future studies to explore both potential mechanisms associated with burn-related neurologic damage and associated functional impairments.

Hemorrhagic shock induces immune dysfunction via mesenteric lymph return, leading to systemic inflammatory response and multiple organ dysfunction. Dendritic cells (DCs) play a pivotal role in immune response following hemorrhagic shock. Therefore, identifying regulatory targets within DCs is essential for understanding hemorrhagic shock-induced immune dysfunction. Endoplasmic reticulum autophagy (ER-phagy), a selective form of autophagy, is critical for DC function. Here, we investigated the role of tumor necrosis factor-α-induced protein-8-like 2 (TIPE2), a protein known to regulate autophagy, in modulating DC ER-phagy after hemorrhagic shock. We analyzed the function and ER-phagy in splenic DCs from wild-type (WT) mice following hemorrhagic shock in vivo and DCs stimulated with post-hemorrhagic shock mesenteric lymph (PHSML) in vitro. Our results showed an increased number of autophagosomes containing endoplasmic reticulum (ER) structures, with significantly enhanced colocalization between ER and autophagosomes in DCs during hemorrhagic shock. The proliferation of CD4+ T cells co-cultured with DCs was weakened, and the expression of surface molecules on the DCs was significantly increased after stimulation with PHSML. Subsequently, WT, TIPE2-/- and TIPE2+/+ mice were used to further analyze the correlation between TIPE2 and ER-phagy in the context of hemorrhagic shock. The results demonstrated that under hemorrhagic shock conditions, TIPE2-/- mice exhibited a significantly reduced LC3-II/I ratio and elevated SEC61B expression in the spleen tissue compared to WT mice, suggesting a diminished level of ER-phagy. Conversely, TIPE2+/+ mice showed the opposite changes. Following stimulation with PHSML, the findings revealed a marked increase in the colocalization between ER and autophagosomes and a significant inhibition of DC function compared to the control group. Additionally, the deletion of TIPE2 weakened ER-phagy and decreased the inhibitory effect on DC function. In contrast, the overexpression of TIPE2 further enhanced ER-phagy and intensified the inhibition of DC function. In addition, TIPE2 is involved in the regulation of the non-classical ER-phagy receptor tripartite motif 13 (TRIM13) expression. These results suggest that ER-phagy is enhanced in DCs after hemorrhagic shock and that TIPE2 may regulate ER-phagy and DC function via TRIM13. This research provides a theoretical basis for future clinical therapeutic strategies targeting the regulation of ER-phagy to improve the function of DCs.

Background: Sepsis is a severe systemic inflammatory response, typically triggered by infection. When the body's response to infection becomes dysregulated, it can result in organ dysfunction, tissue damage, and even death. Sepsis can affect people of all ages, but older adults, individuals with weakened immune systems, and those with chronic illnesses are at greater risk. Timely diagnosis and immediate intervention are essential to enhance the chances of survival.

Objective: This study aims to develop a mortality risk prediction model for sepsis patients utilizing tree-based ensemble classifiers, with post-hoc interpretation through Shapley Additive Explanations (SHAP), to support clinical decision-making.

Methods: Clinical data of sepsis patients admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Xinjiang Medical University were collected. The mice package was used to handle missing data, and the Synthetic Minority Oversampling Technique(SMOTE) algorithm was applied to oversample the minority class to address data imbalance. We applied seven models, including Random Forest(RF), k-Nearest Neighbors(KNN), Support Vector Machine (SVM), logistic regression, eXtreme Gradient Boosting (XGBoost), Logistic_Lasso Regression (Logistic_Lasso), and Light Gradient Boosting Machine (LightGBM), and compared their prediction performance using the area under the receiver operating characteristic curve (AUC), Precision-Recall Curve (PR), and Decision Curve Analysis (DCA). Based on these models, we applied both global and local interpretation approaches to elucidate model predictions and explore prognostic risk factors in sepsis patients.

Results: The RF model showed the best performance among the seven Machine Learning (ML) models, achieving an AUC of 0.9816. Both global and local explainability techniques were applied to interpret the decision-making mechanisms of the ML models.

Conclusion: Local explanation methods can interpret how ML models make predictions for individual outcomes. Global interpretation techniques help reveal how ML models respond across the entire feature landscape.