SHOCK最新文献

Background: Intestinal barrier disruption is central to heat stroke (HS) pathogenesis. Probiotics like Bifidobacterium may offer protection. This study aimed to investigate the mechanism by which Bifidobacterium preserves intestinal mucosal barrier integrity in a rat model of HS.

Methods: 32 rats received Bifidobacterium (Con-BB, HS-BB) or saline (Con-NS, HS-NS) for 14 days. HS was induced via forced running in heat/humidity. Serum markers (tissue damage, inflammation, barrier injury), histopathology, and gut microbiota were analyzed.

Results: Compared with the HS-NS group, the HS-BB group showed a marked reduction in the characteristic histopathological injuries of the liver, kidney, and intestine, along with increased expression of ileal ZO-1 and colonic Occludin proteins (P < 0.05). Serum biomarkers reflecting tissue damage (TBIL, LDH) and inflammation (IL-6) were all significantly decreased in the HS-BB group (P < 0.05). Gut microbiota composition differed markedly between the HS-BB and HS-NS groups; Psychrobacter abundance was significantly reduced in HS-BB and identified as a key discriminator. Furthermore, expression of heat shock proteins (HSP) (colonic HSP27 and HSP70) was significantly elevated in HS-BB compared to the HS-NS group. Strong positive correlations existed between ileal Occludin and HSP27 (r = 0.886, P = 0.019), and ileal ZO-1 and HSP70 (r = 0.829, P= 0.042).

Conclusions: Bifidobacterium pretreatment conferred significant multi-organ protection and reduced systemic inflammation in HS rats. The core protective mechanism involves preserving intestinal mucosal barrier function. Maintaining intestinal mucosal barrier integrity may represent a promising strategy for the prevention of HS and the mitigation of associated systemic inflammatory responses and multiple organ dysfunction syndrome (MODS).

Background: While CD8+ T-cell subsets play a crucial role in sepsis prognosis, the prognostic value of their dynamic changes and molecular mechanisms remains incompletely understood. Compared to static single-timepoint measurements, the prognostic role of repeated measurements over time remains undetermined.

Methods: The study included 220 intensive care unit patients with sepsis (2023.08-2024.05). K-means clustering analysis based on CD8+CD28+/CD8+%, CD8+CD38+/CD8+%, and CD8+DR+/CD8+% was used to categorize patients into two groups. Clinical data were collected and analyzed for 28-day mortality prediction. Fifteen patients from each group were selected for Olink proteomics analysis to investigate differentially expressed proteins and conduct functional enrichment analysis.

Results: Using K-means clustering analysis based on CD8+ T-cell subset phenotypes, patients were divided into group 1 (n = 74) and group 2 (n = 146), with group 2 demonstrating significantly higher 28-day mortality compared to group 1 (32.3% vs. 17.6%, P < 0.001). Further dynamic trend analysis revealed that patients exhibiting continuously decreasing CD8+CD28+/CD8+% and increasing CD8+CD38+/CD8+% had the poorest prognosis, with a 28-day mortality rate of 50%. The combined measurement of CD8+CD28+/CD8+% and CD8+CD38+/CD8+% showed enhanced prognostic value (area under the curve = 0.676) compared to individual measurements, indicating the importance of monitoring multiple T-cell subset markers. Additionally, Olink proteomic analysis identified IL-12Rβ1 as a key molecular mediator closely associated with CD8+ T-cell function and activation subsets, providing insights into the underlying mechanism of immune dysfunction in sepsis patients.

Conclusions: CD8+ T-cell subset phenotypes serve as important prognostic indicators in sepsis, with IL-12Rβ1 potentially being a key molecule affecting CD8+ T-cell function, providing a new potential target for sepsis monitoring and immunotherapy.

Objective: Sepsis-induced muscle atrophy significantly impairs patient quality of life, yet effective therapeutic strategies remain limited. This study aimed to investigate the protective effects of selenomethionine (Se-Met) on sepsis-induced skeletal muscle atrophy and explore the underlying molecular mechanisms, with the goal of providing a novel theoretical foundation and potential therapeutic approach for sepsis-associated muscle injury.

Methods: A murine sepsis model was established via cecal ligation and puncture, followed by treatment with varying doses of Se-Met. Survival rate, body weight, skeletal muscle mass, and muscle strength were evaluated. Histological analysis [hematoxylin and eosin (HE) staining] was used to assess muscle fiber cross-sectional area. Protein expression levels of Atrogin-1, MuRF1, and pyroptosis-related markers (NLRP3, Caspase-1, GSDMD, IL-18, and IL-1β) were examined via Western blot. In vitro , C2C12 myoblasts were stimulated with lipopolysaccharide and treated with Se-Met to assess oxidative stress markers [reactive oxygen species (ROS), malondialdehyde, superoxide dismutase, glutathione peroxidase], pyroptosis-related proteins, and inflammatory cytokines (e.g., IL-6 and IL-18). ROS scavenger N-acetylcysteine, NLRP3 agonist, and ROS inducer were employed in mechanistic studies to further elucidate the molecular mechanisms.

Results: Se-Met significantly improved survival, body weight, and muscle strength in septic mice and alleviated skeletal muscle atrophy. Mechanistically, Se-Met inhibited the NLRP3/Caspase-1/GSDMD signaling axis, thereby reducing pyroptosis and the expression of inflammatory cytokines such as IL-6, IL-18, and IL-1β. Furthermore, Se-Met decreased ROS accumulation, enhanced antioxidant enzyme activities, and suppressed pyroptosis through regulation of the ROS/NLRP3 pathway, ultimately reducing protein degradation mediated by Atrogin-1 and MuRF1.

Conclusion: This study demonstrates that Se-Met mitigates sepsis-induced skeletal muscle atrophy by exerting antioxidant effects, inhibiting pyroptosis, and modulating inflammatory responses. The findings highlight the critical role of the ROS/NLRP3 signaling pathway in the protective action of Se-Met, providing new experimental evidence for its potential application in sepsis and other oxidative stress-related diseases.

Introduction: Traumatic brain injury (TBI) is an underrecognized public health threat that can lead to long-term complications for its survivors. Monocytes are among the first immune cells recruited after TBI and interact with the microglia-the resident innate immune cells. Which drives the direction of the inflammatory response of the brain. Published data from our laboratory have shown that a brief course of peri-injury monocyte depletion attenuates long-term neurocognitive deficits and preserves white matter connectivity postinjury. To this end, we hypothesized that infiltrating monocytes shape the long-term transcriptional response of microglia after TBI.

Methods: Male C57BL/6 were randomly assigned to experimental groups-TBI, sham, TBI with monocyte depletion, and TBI with vehicle. Depletion was induced via intravenous injection of liposome-encapsulated clodronate versus naked liposomes 24 hours before injury and maintained by repeat injections. Behavioral phenotyping was done 30 days postinjury. Mice were euthanized, brains were harvested, and microglia were sorted via flow cytometry. Lastly, bulk RNA sequencing was conducted.

Results: Monocyte-depleted mice demonstrated improvement in motor coordination, contextual and associative learning, and memory. This was associated with different transcriptional profiles at acute injury. A distinct upregulation of signal transduction pathways and heat shock protein transcripts was also observed as compared with the vehicle TBI groups.

Conclusion: These data show that a short course of peri-injury depletion of peripheral monocytes may have a neuroprotective effect after TBI. Alteration of the long-term transcriptional profile of microglia may be responsible for the observed changes in behavior. These data warrant further investigation into the possible therapeutic benefits of peri-injury immune modulation.

Mortality from major bleeding in trauma patients is highest within the first 6 hours postinjury. Advances in patient management, driven by national guidelines and clinical trials, have significantly improved outcomes. However, variability in patient profiles, clinical presentations, and standard-care practices complicates the assessment of treatment efficacy in clinical trials. In June 2024, international experts convened at the Critical Care Clinical Trialists (3CT) Workshop to examine the evolution of massive bleeding management and the impact of patient and treatment heterogeneity on trial design. This opinion article builds on the workshop discussions and underscores key considerations for the interpretation of large-scale studies. Three main conclusions emerged: First, the need for standardized definitions of "massive bleeding," "life-threatening bleeding," and "massive transfusion" to ensure consistent patient classification and treatment strategies. Second, the importance of tailored approaches that account for patient heterogeneity, including the careful selection of target populations and the use of appropriate primary endpoints. Third, the necessity of methodological adaptations in emergency research settings, such as implementing deferred consent procedures, conducting interim analyses, and using automated adjudication systems to improve objectivity and trial efficiency. In summary, harmonizing terminology, embracing clinical diversity, and refining trial design are essential to enhance the quality, comparability, and clinical relevance of research in massive bleeding. These measures ultimately aim to improve outcomes for critically bleeding patients.

Introduction: Low-titer O positive whole blood (LTOWB) has been introduced in prehospital care to resuscitate patients; however, the logistical obstacles, cost of carrying LTOWB, and the availability of it in trauma situations are a point of concern. Therefore, fluids, like lactated Ringer's (LR) and hydroxyethyl starch (HES), have been considered alternatives to LTOWB transfusion. Unfortunately, they dilute plasma proteins in the circulation and have unfavorable side effects. This study presents an alternative, a protein cocktail (PC). The PC combines human serum albumin, transferrin, haptoglobin, and hemopexin. This study compares the ability to resuscitate from hemorrhagic shock (HS) with whole blood (WB), LR, 6% HES, and PC.

Methods: Unanesthetized golden Syrian hamsters instrumented with the dorsal window chambers were subjected to hemorrhage (50% blood volume), followed by 30 min hypovolemic shock, and resuscitated with 50% shed volume. The outcome was evaluated through systemic parameters, blood gases, microcirculatory hemodynamics, oxygen tension and saturation, metabolomics, and markers of organ injury/function. Additionally, to investigate the impact of the experimental solutions on the coagulation cascade, Sprague-Dawley rats were subjected to an isovolemic exchange infusion of 20% of the animal's blood volume.

Results: The PC showed favorable outcomes, restoring microvasculature hemodynamics comparable to resuscitation with WB and superior to LR and HES. PC reduced acute inflammation, positively impacted organ function markers, and restored metabolomic homeostasis without coagulopathies observed with HES.

Conclusion: In conclusion, the PC shows some promise as a resuscitation from HS when WB is not available and superior to classic crystalloids and colloids (LR and HES). Further studies with the PC are needed to ensure its efficacy and safety in other experimental models.

Objective: This study aims to systematically evaluate the risk factors associated with the development of postoperative lower extremity deep venous thrombosis (LEDVT) in patients with severe traumatic brain injury (sTBI).

Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comprehensive searches of Chinese and English databases, including PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang, were conducted from inception to December 12, 2024. Two researchers independently screened articles and extracted relevant data. Study quality was assessed using the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality criteria. Meta-analyses were performed using RevMan 5.3, applying a random-effects model to combine effect sizes, with subsequent sensitivity analyses and assessments for publication bias. The review was registered in PROSPERO (CRD42024629624).

Results: A total of 13 studies (n = 777,327) were included, comprising 8 case-control studies, 2 cohort studies, and 3 cross-sectional studies. Eleven significant risk factors for postoperative LEDVT were identified: advanced age (odds ratio [OR] = 1.12, 95% confidence interval [CI]: 1.10-1.14), use of dehydrant (OR = 2.04, 95% CI: 1.38-3.04), mechanical ventilation (OR = 1.01, 95% CI: 1.01-1.02), elevated D-dimer level (OR = 1.19, 95% CI: 1.11-1.27), polytrauma (OR = 1.63, 95% CI: 1.29-2.03), hypertension (OR = 1.11, 95% CI: 1.07-1.15), surgical duration (OR = 1.60, 95% CI: 1.06-2.42), elevated body mass index (OR = 1.30, 95% CI: 1.16-1.45), deep venous catheterization (OR = 1.36, 95% CI: 1.15-1.60), length of hospital stay (OR = 1.36, 95% CI: 1.18-1.56), and blood transfusion (OR = 3.56, 95% CI: 1.91-6.63), with all P values <0.05. No statistically significant associations were observed for Glasgow Coma Scale score (OR = 1.12, 95% CI: 0.98-1.28) or diabetes mellitus (OR = 1.02, 95% CI: 0.97-1.07).

Conclusions: Eleven variables were identified as significant risk factors for postoperative LEDVT among patients with sTBI. These findings underscore the importance of implementing individualized preventive strategies for patients identified as high risk.

Background: Thiamine has been utilized for metabolic resuscitation in septic shock (SS), but optimal thiamine dosing remains unknown. The purpose of this study was to assess variable thiamine dosing in critically ill patients with SS.

Methods: This retrospective, cohort study included SS patients on high-dose (HD >500 mg/d) or low-dose (LD ≤500 mg/d) thiamine for 72 hours without an alternative indication. The primary endpoint was to evaluate the impact of HD or LD thiamine on vasopressor alive-and-free days.

Results: The analysis included 87 patients who received HD thiamine and 65 patients who received LD thiamine. The mean thiamine dose was 1.485.6 mg/d in the HD group and 323.8 mg/d in the LD group. The HD group more often utilized 30 mL/kg of intravenous fluid resuscitation (89% vs. 82%) and hydrocortisone at 300 mg/d (69% vs. 58%). Results found vasopressor alive-and-free days to be 17.13 in the HD group and 14.84 days in the LD group. No statistically discernible differences were found between the groups in 28-day mortality, intensive care unit length of stay, vasopressor free days, percentage decrease in lactate or serum creatinine, need for additional vasopressor(s), or hospital length of stay, although some of the observed differences are believed to be clinically meaningful.

Conclusion and relevance: Patients with SS who received HD thiamine had no statistically discernible differences in vasopressor alive-and-free days or intensive care unit length of stay as compared to the LD thiamine group. Larger, prospective, randomized trials are warranted to further investigate HD thiamine in critically ill patients with SS.

Purpose: Brain dysfunction is a significant complication of sepsis, commonly referred to as sepsis-associated encephalopathy (SAE). Alterations in gut microbiota during sepsis may contribute to development of SAE through the gut-brain axis. This study investigated effects of fecal transplantation from healthy or endotoxemic individuals on gut microbiota and brain function in a rat model of LPS-associated encephalopathy.

Methods: Following LPS induction, rats received daily oral gavage of fecal microbiota transplants for 3 days. Sensory and motor functions were assessed daily throughout the 7-day study period after LPS exposure. On day 7 post-LPS, the study examined gut microbiota structure and composition, serum and fecal short-chain fatty acids (SCFAs) levels, ileal villus length, intestinal permeability, neuronal and glial ultrastructure, cytokine concentrations (pro-inflammatory and anti-inflammatory), and mitochondrial bioenergetics.

Results: Administration of healthy donor feces preserved gut microbial structure and composition, maintained ileal villus length, and improved intestinal permeability following LPS treatment. Additionally, it increased SCFA levels, reduced pro-inflammatory cytokines, enhanced anti-inflammatory cytokine release, and restored sensitivity to mechanical and thermal stimuli, as well as motor function. Rats treated with healthy donor feces also exhibited reduced neuronal necrosis and a decreased density of mitochondria in cortical astrocytes. Notably, mitochondrial metabolism in LPS-treated rats returned to near-normal levels following treatment with healthy donor feces. In contrast, administration of endotoxemic donor feces exacerbated these effects in LPS-treated rats.

Conclusion: Ameliorating gut dysbiosis prevents mitochondrial dysfunction in astrocytes by promoting SCFA production and enhancing anti-inflammatory cytokine release. This process preserves neuronal integrity and mitigates the severity of encephalopathy.

Sepsis, a dysregulated host response to infection, remains a growing global health concern, particularly in older adults. While much attention focuses on acute survival, an increasing number of sepsis survivors experience persistent neurological complications, including impairments in memory, attention, and executive function. In severe cases, these may manifest as sepsis-associated delirium or progress to long-term cognitive impairment and dementia. The mechanisms driving these outcomes are complex and incompletely understood, partly due to limited baseline cognitive data and significant variability among older adults. A central feature of sepsis-induced brain dysfunction is sustained neuroinflammation, which bridges peripheral immune activation and central nervous system injury. Mounting evidence implicates macrophages, including circulating monocytes and brain-resident microglia, as key regulators of this neuroimmune axis. Inflammatory conditions during sepsis often drive macrophage polarization toward a pro-inflammatory M1 phenotype, leading to the release of cytokines and reactive oxygen species that exacerbate blood-brain barrier disruption and neuronal injury. Conversely, impaired transition to the M2 phenotype hinders inflammation resolution and tissue repair. Critically, this interaction is bidirectional, where neuroinflammatory signals from activated microglia can influence peripheral macrophage behavior, creating a self-reinforcing inflammatory loop that may prolong central nervous system damage. This process is especially concerning in older adults who may have preexisting immune vulnerabilities and varying baseline cognitive status, which presents unique challenges for therapeutic targeting. This review highlights the central and dynamic role of macrophage polarization in sepsis-associated cognitive decline. Understanding how systemic and neuroinflammatory pathways converge through macrophage signaling may reveal new therapeutic targets to mitigate long-term neurological complications in sepsis survivors. Graphical abstract-Sepsis alters the abundance and polarization of macrophage subpopulations, contributing to both short- and long-term cognitive impairment. In the acute phase, these changes may manifest as sepsis-associated delirium (SAD), while in the long term, sustained immune dysregulation and neuroinflammation may contribute to persistent cognitive deficits, including memory loss and executive dysfunction.