SHOCK最新文献

{"title":"Assessment of Novel Platform of Thrombin Generation to Predict Venous Thromboembolism Early After Traumatic Injury: A Prospective Cohort Study.","authors":"Sergio M Navarro, Riley J Thompson, Taleen A MacArthur, Grant M Spears, Kent R Bailey, Dong Chen, Rajiv Pruthi, Donald H Jenkins, Jing-Fei Dong, Rosemary A Kozar, Myung S Park","doi":"10.1097/SHK.0000000000002725","DOIUrl":"10.1097/SHK.0000000000002725","url":null,"abstract":"<p><strong>Introduction: </strong>Calibrated automated thrombogram assay parameters have been shown to assess hypercoagulation state and, therefore, may independently predict posttrauma, symptomatic venous thromboembolism (VTE). Yet, calibrated automated thrombogram lacks high throughput and standardization, limiting diagnostic potential. This study analyzed thrombin generation (TG) profiles in trauma patients using a high-throughput assay, processing up to 10 samples at once, providing batch testing capabilities. We hypothesized that trauma patients who developed VTE would show distinct TG profiles compared with those who did not.</p><p><strong>Methods: </strong>Trauma patients presenting to a Level I Trauma Center had samples collected within 12 hours postinjury prospectively. Follow-up was conducted to 90 days, time to symptomatic VTE diagnosis or death, confirmed via autopsy or imaging. TG profiles were measured from the ST Genesia assay. Data were presented as median (interquartile ranges) or n (%), with the Wilcoxon rank-sum or chi-squared test. Associations between TG parameters and clinical risk factors were assessed using Spearman correlation analysis or the Wilcoxon rank-sum test.</p><p><strong>Results: </strong>Two hundred and fifty-four trauma patients were analyzed [48.5 years (31.0, 62.0), 72.0% male]: 64 patients with VTE (25.2%) to 190 with non-VTE. VTE pts had a median time to VTE of 8 days, with 29 developing deep venous thrombosis, 24 with pulmonary embolism, and 11 with deep venous thrombosis/pulmonary embolism. No significant differences were found in age, sex, or body mass index; significantly more VTE patients underwent surgery and blood transfusions within 24 hours. TG profiles demonstrated accelerated TG in patients who developed VTE compared with non-VTE, with significant differences in peak height ( P = 0.001), time to peak ( P = 0.021), endogenous thrombin potential ( P < 0.001), and velocity index ( P = 0.001).</p><p><strong>Conclusion: </strong>TG profiles using ST Genesia can differentiate trauma patients at high risk of developing VTE. The platform suits clinical labs needing high throughput by providing batch testing capabilities.</p><p><strong>Study type: </strong>Prospective study with less than large effect and no negative criteria.</p><p><strong>Level of evidence: </strong>II.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"441-448"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13426469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147634379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal Aquaporin Expression Profiles in Immune Cell Subsets During Critical Illness.","authors":"Nikolaos S Lotsios, Vasileios Issaris, Georgios Poupouzas, Charikleia S Vrettou, Chrysi Keskinidou, Matina Kardara, Kostas A Papavassiliou, Foteini Economidou, Stelios Kokkoris, Anastasia Kotanidou, Ioanna Dimopoulou, Alice G Vassiliou","doi":"10.1097/SHK.0000000000002883","DOIUrl":"10.1097/SHK.0000000000002883","url":null,"abstract":"<p><p>Aquaporins (AQPs) are a family of water channel proteins with a significant role in immune cell function. Although AQPs have been studied in sepsis, their expression in critical illness remains underexplored. Our group aimed to examine the mRNA expression profile of AQP isoforms in polymorphonuclear leukocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) of critically ill patients admitted to the intensive care unit (ICU). To this end, we designed a prospective, longitudinal, observational study performed in the ICU of \"Evangelismos\" General Hospital between February 2024 and October 2024. In total, 40 critically ill patients and 25 healthy controls were enrolled in the study. Blood samples were collected at four time points: upon ICU admission (24-48 hours), and at days 4 (D4), 8 (D8), and 14 (D14). Total RNA was extracted from PMNs and PBMCs, and RT-qPCR was performed to examine mRNA levels of AQPs 1, 2, 3, 4, 5, 7, and 9. Our results revealed downregulation of AQP isoforms, except AQP1, in PMNs, whereas PBMCs exhibited sustained upregulation of all AQPs except AQP3, which was downregulated. Our findings suggest that differential AQP expression in immune cell subsets may reflect adaptive immune responses during critical illness, providing insights into leukocyte function and potential therapeutic targets.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"367-376"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Impact and Risk Factors of Septic Cardiomyopathy in Patients with Septic Shock: An Observational Study.","authors":"Rui-Ming Xu, Da-Wei Wang, Lei Wang, Jian-Zhong Li, Yan-Yun He, Jing Zhang","doi":"10.1097/SHK.0000000000002782","DOIUrl":"10.1097/SHK.0000000000002782","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to identify risk factors associated with septic cardiomyopathy (SCM) in patients diagnosed with septic shock and to assess differences in clinical outcomes between those with septic shock alone and those with concomitant SCM.</p><p><strong>Methods: </strong>A retrospective observational study was conducted on 108 patients diagnosed with septic shock and admitted to Beijing Tongren Hospital, Capital Medical University, between December 2022 and July 2024. Patients were stratified into two groups based on the presence or absence of SCM: the non-SCM group (n = 90) and the SCM group (n = 18). Baseline characteristics, laboratory markers, cardiac function indices, and clinical outcomes were compared between the two groups. Multivariate logistic regression was employed to identify risk factors for SCM. Within the SCM group, outcomes were further analyzed according to survival status to assess the association between cardiac function recovery and mortality.</p><p><strong>Results: </strong>The incidence of SCM among patients with septic shock was 16.67%. Compared with the non-SCM group, the SCM group showed a significantly higher prevalence of urinary tract infections and a history of diabetes mellitus ( P < 0.05). Higher scores were observed for the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment scales, along with increased levels of admission-day troponin I, interleukin-1 (IL-1), tumor necrosis factor-α, maximum lactic acid (LACmax), maximum brain natriuretic peptide, and peak troponin I ( P < 0.05). In contrast, mean arterial pressure at admission, minimum left ventricular ejection fraction (LVEF), and end-point LVEF (LVEFend%) were significantly lower in this group ( P < 0.05). Multivariate logistic regression identified elevated IL-1 levels (odds ratio [OR] = 1.14), higher APACHE II scores (OR = 1.13), and increased LACmax (OR = 1.47) as risk factors for SCM ( P < 0.05). The presence of SCM was associated with significantly higher in-hospital mortality and increased healthcare costs ( P < 0.05). Among patients with SCM, recovery of LVEF and cardiac output was correlated with improved survival outcomes.</p><p><strong>Conclusions: </strong>Elevated IL-1 levels, increased peak lactic acid concentration, and higher APACHE II scores were associated with the development of SCM in patients with septic shock. SCM was further associated with increased mortality and greater healthcare resource utilization. Restoration of cardiac function, particularly improvements in LVEF and cardiac output, was correlated with improved prognosis and may serve as a valuable indicator of clinical outcomes.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"340-347"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early STAT3 Activation and Delayed STAT5 Dominance Define the Acute Leukocyte Signaling Response to Trauma and May Correlate with Clinical Outcomes.","authors":"Matthew Montoya Rush, Mark H Hoofnagle, Grace M Niziolek, Sarbani Ghosh, Philip C Spinella, Grant V Bochicchio, Isaiah R Turnbull","doi":"10.1097/SHK.0000000000002881","DOIUrl":"10.1097/SHK.0000000000002881","url":null,"abstract":"<p><p>Major trauma dysregulates the immune system, leaving injured patients at increased risk of infection. Despite extensive research to define the effect of trauma on the immune system, there are no effective interventions to restore immune function in injured patients. We previously used single-cell phosphoproteomics to identify pathways for immunomodulation in COVID-19 induced critical illness. We hypothesized that trauma would also be associated with definable changes in leukocyte signaling, providing therapeutic targets. To test this hypothesis, we used mass cytometry to assess signaling phosphoproteins and associated surface markers at single-cell resolution in a cohort of critically injured patients. We find that injury causes an acute increase in STAT3 signaling across leukocyte populations, followed by a shift from STAT3 to STAT5 predominance in T cells over the first 72 hours after injury. We used computational clustering to identify subpopulations of T cells and found that injury causes an increase in activated CD4 memory T cells. We assessed the relationship between phosphoprotein levels and clinical outcomes and identified significant correlations between early phospho-STAT3 levels in T cells, monocytes, and neutrophils and clinical outcomes, including ICU and hospital length of stay. These data demonstrate that severe injury is associated with cell-type-specific changes in the signaling phosphoproteome in circulating leukocytes, which may underlie clinical outcomes from injury.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"385-394"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148332368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synopsis Shock August 2026.","authors":"","doi":"10.1097/SHK.0000000000002897","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002897","url":null,"abstract":"","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":"66 2","pages":"275-278"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Validation of Key Genes Related to Arginine Methylation Modification in Sepsis Using Transcriptome Combined with Mendelian Randomization Analysis.","authors":"Peng Huang, Meifeng Wang, Weihong Hong, Jinyuan Kang, Yuyang Li, Ying Li, Xiao Lin","doi":"10.1097/SHK.0000000000002741","DOIUrl":"10.1097/SHK.0000000000002741","url":null,"abstract":"<p><strong>Background: </strong>Patients with sepsis often exhibit a decrease in lymphatic numbers, which can be facilitated by protein arginine methyltransferase (PRMT). However, it is unclear how PRMT contributes to lymphopenia in sepsis.</p><p><strong>Methods: </strong>This study employed the sepsis-related datasets (GSE65682 and GSE134347) and nine PRMT genes. First, we intersected the differentially expressed genes with the weighted gene co-expression network analysis module genes to identify differentially expressed PRMT-related genes. Thereafter, candidate key genes were obtained after Mendelian randomization analysis and machine learning screening. Eventually, we subjected key genes identified by expression analysis and receiver operating characteristic curves to gene set enrichment analysis, immune infiltration analysis, immune checkpoint analysis, molecular docking, regulatory networks construction, and nomogram development.</p><p><strong>Results: </strong>We first intersected 4,246 differentially expressed genes with 1,884 PRMT scoring module genes to obtain 969 differentially expressed PRMT-related genes. Further Mendelian randomization analysis and machine learning jointly identified five candidate genes ( CRLF3 , ELAC2 , PBX2 , MCTP2 , and EMB ). Among these, ELAC2 , PBX2 , MCTP2 , and EMB demonstrated consistent expression trends, with the area under the curve values of the receiver operating characteristic curve exceeding 0.7 in GSE65682 and GSE134347. Therefore, they were defined as key PRMT-related genes. The gene set enrichment analysis showed enrichment in cytoplasmic translation ( ELAC2 , MCTP2 ), noncoding RNA metabolism ( EMB ), and metabolic processes ( PBX2 ). The immune infiltration analysis revealed a significant correlation between PBX2 and neutrophils, as well as between ELAC2 / MCTP2 / EMB with activated natural killer cells, CD8+ T cells.</p><p><strong>Conclusion: </strong>In this study, ELAC2 , PBX2 , MCTP2 , and EMB were identified as key genes related to PRMT for sepsis, which provided a theoretical basis for the study of sepsis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"424-440"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13384385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nutritional Status-Based Model for Predicting Low-Lactate Shock: A Retrospective Cohort Study.","authors":"Xiaofang Xu, Fang Hu, Zhaocai Zhang","doi":"10.1097/SHK.0000000000002710","DOIUrl":"10.1097/SHK.0000000000002710","url":null,"abstract":"<p><strong>Background: </strong>Although Sepsis-3.0 defines septic shock as hypotension with serum lactate levels >2.0 mmol/L, this criterion may miss low-lactate shock: a clinically significant phenotype characterized by hypotension but without elevated lactate levels. The epidemiological characteristics and prognostic significance of low-lactate shock remain unclear, highlighting a critical gap in current shock management models.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of 3,134 patients with shock admitted to a tertiary care medical institution from January 2015 to March 2022. We used propensity score matching (1:2 ratio) to control for confounding factors, aiming to determine the prevalence of low-lactate shock (lactate ≤ 2.0 mmol/L), identify risk factors through multivariable logistic regression, and validate the predictive model [Nutritional Risk Screening-2002-Acute Physiology and Chronic Health Evaluation-Triglycerides-Total Bilirubin (NRS-APACHE II-TG-TBIL)] using receiver operating characteristic analysis.</p><p><strong>Results: </strong>The 28-day mortality rate was slightly lower in the low-lactate shock group compared with the high-lactate group [25.4% (94/369) vs. 35.8% (990/2,765), respectively]. The age, Nutritional Risk Screening-2002 (NRS-2002) score, and venous thromboembolism risk score were significantly lower in the low-lactate shock group than in the high-lactate shock group ( P < 0.05). No statistically significant differences were observed in gender distribution ( P = 0.092). Multivariable analysis identified four independent predictors of low-lactate shock: NRS-2002 [odds ratio (OR) = 0.570, P < 0.001], Acute Physiology and Chronic Health Evaluation II (APACHE II) (OR = 0.869, P < 0.001), triglycerides (OR = 0.772, P = 0.035), and total bilirubin (OR = 0.993, P = 0.002). The composite NRS-APACHE II-TG-TBIL model showed excellent discrimination (area under curve = 0.800, P < 0.001) with balanced sensitivity (72.6%) and specificity (73.5%).</p><p><strong>Conclusions: </strong>Low-lactate shock carries substantial mortality risk (25.4%). The validated NRS-APACHE II-TG-TBIL model (area under curve = 0.800) provides an effective tool for early detection, addressing critical diagnostic gaps in shock management.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"323-332"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13384367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual Targeting of Net Formation and Coagulation Improves Survival and Organ Protection in Experimental Sepsis.","authors":"Xiangqun Zhang, Junyuan Wu, Shubin Guo","doi":"10.1097/SHK.0000000000002824","DOIUrl":"10.1097/SHK.0000000000002824","url":null,"abstract":"<p><strong>Objective: </strong>Sepsis is a life-threatening critical illness characterized by dysregulated host responses, in which excessive neutrophil extracellular trap (NET) formation and sepsis-associated coagulopathy play central roles in organ dysfunction and mortality. Targeting a single pathological pathway has shown limited clinical benefit. Cl-amidine, a peptidylarginine deiminase 4 inhibitor, suppresses NET formation, whereas heparin is widely used in critically ill patients to modulate coagulation and neutralize histone-mediated cytotoxicity. Whether simultaneous targeting of NET-driven inflammation and coagulation dysregulation provides enhanced protection in sepsis remains unclear.</p><p><strong>Methods: </strong>Sepsis was induced in C57BL/6J mice using the cecal ligation and puncture model. Mice received postinsult treatment with Cl-amidine (50 mg/kg, intraperitoneally) and/or heparin (1,000 U/kg, intravenously). Seven-day survival was assessed. Circulating NET-related markers (citrullinated histone H3 and myeloperoxidase), inflammatory cytokines, coagulation parameters, and histopathological injury of the lung, liver, and kidney were evaluated.</p><p><strong>Results: </strong>Combined treatment with Cl-amidine and heparin significantly improved 7-day survival compared with untreated septic mice, whereas Cl-amidine monotherapy did not confer a survival benefit despite significantly reducing NET markers. Cl-amidine significantly reduced NET formation, whereas heparin alone did not show a statistically significant effect on NET markers. Combined treatment further enhanced the reduction of myeloperoxidase levels. Histopathological analysis demonstrated that pulmonary, hepatic, and renal injury were most markedly attenuated in the combination group compared with either monotherapy. Although inflammatory and coagulation parameters were generally improved following treatment, the effects of the combined regimen were comparable to those of the more effective monotherapy for several markers, and no statistically confirmed pharmacological synergy was observed.</p><p><strong>Conclusions: </strong>Combined administration of Cl-amidine and heparin provides a meaningful survival benefit and attenuates multiorgan injury in experimental sepsis. Although no statistically confirmed pharmacological synergy was observed across all parameters, the combined intervention exerted additive protective effects beyond single-agent treatment. Importantly, the additional histological protection could not be explained by further suppression of systemic cytokines or by changes in global coagulation parameters, and the underlying mechanisms therefore remain incompletely defined. Further preclinical studies addressing bleeding risk, optimal dosing strategies, and mechanistic pathways are warranted before clinical translation.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"550-559"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13384365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147532321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology and Risk Factors of Sepsis and Sepsis-Induced Myocardial Dysfunction in the Intensive Care Units of Tertiary Hospitals.","authors":"Gui-Jun Zhu, Yan Huo, Yu-Chun Yin, Bo Li, Zhenjie Hu","doi":"10.1097/SHK.0000000000002685","DOIUrl":"10.1097/SHK.0000000000002685","url":null,"abstract":"<p><p>Sepsis and sepsis-induced myocardial depression (SIMD) are critical conditions associated with high mortality in intensive care units (ICUs). This study aimed to characterize the clinical profiles of sepsis and SIMD in tertiary ICUs, identify prognostic determinants, and enhance understanding of outcome-related risk factors. We conducted a multicenter observational study involving sepsis patients admitted to 30 tertiary ICUs in Hebei Province, China, between May and September 2016. Each patient underwent echocardiography, with left ventricular ejection fraction measured via Simpson's method to assess myocardial dysfunction. Comprehensive clinical data were collected and analyzed. Among 4,897 enrolled patients, sepsis prevalence was 31.48%, with a 28-day mortality rate of 27.40%. Among them, 486 patients had septic shock, with a prevalence of 9.39% and 28-day mortality of 50.41%, and 234 had sepsis-induced myocardial depression, with a prevalence of 4.79% and 28-day mortality of 42.31%. Univariate analysis identified significant associations between survival outcomes and age, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment score, Multiple Organ Dysfunction Syndrome, left ventricular ejection fraction, lactate, white blood cell, procalcitonin (PCT), and C-reactive protein. Multivariate analysis demonstrated that age, APACHE II score, lactate, and PCT were independent risk factors for sepsis mortality, while APACHE II score and PCT independently predicted mortality in SIMD patients. The lungs and abdomen were the most common infection sites. Prognostic stratification should prioritize APACHE II score and PCT, which were consistent independent risk factors for both sepsis and SIMD.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"333-339"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2X7 Receptor Acts as a Novel Target for Ameliorating Sepsis-Induced Skeletal Muscle Atrophy in Mice Model.","authors":"Yukun Liu, Qinxin Liu, Zhikai Xu, Xuan Zhao, Fan Yang, Zhanfei Li, Xiangjun Bai, Jian Yang, Yuchang Wang","doi":"10.1097/SHK.0000000000002703","DOIUrl":"10.1097/SHK.0000000000002703","url":null,"abstract":"<p><strong>Background and objective: </strong>Sepsis, a systemic inflammatory syndrome, frequently leads to substantial skeletal muscle loss and dysfunction, severely impairing patient prognosis. The P2X7 receptor is an adenosine triphosphate-gated cation channel implicated in inflammation and cell death. Although its role in the immune system has been extensively studied, its expression profile and pathogenic mechanism in sepsis-induced skeletal muscle atrophy remain unclear. This study aimed to investigate the functional role of the P2X7 receptor in sepsis-associated muscle injury and its potential as a therapeutic target.</p><p><strong>Methods: </strong>A murine sepsis model was established using cecal ligation and puncture (CLP) surgery. Temporal changes in P2X7 receptor expression in the gastrocnemius (GP) and tibialis anterior (TA) muscles were assessed. Functional studies were performed using P2X7 knockout (P2X7 - / - ) mice and the P2X7-specific antagonist A-740003. Skeletal muscle atrophy, inflammatory responses, and activation of the NLRP3 inflammasome signaling pathway were systematically evaluated through Western blotting, qPCR, hematoxylin-eosin staining, muscle fiber cross-sectional area analysis, and measurement of inflammatory cytokines.</p><p><strong>Results: </strong>In the CLP-induced sepsis model, P2X7 receptor expression in both GP and TA muscles was upregulated in a time-dependent manner. P2X7 gene deletion significantly attenuated body weight loss, muscle mass reduction, and muscle fiber atrophy, restored grip strength, and suppressed the expression of atrophy-related genes (Myostatin, Atrogin-1, and MuRF1). Moreover, it markedly reduced IL-6, IL-18, and IL-1β levels in both skeletal muscle and plasma, indicating an anti-inflammatory effect. P2X7 deficiency also significantly inhibited the expression of NLRP3 inflammasome components, caspase-1, and gasdermin D, thereby blocking the pyroptosis signaling pathway. Pharmacological inhibition with A-740003 showed dose-dependent mitigation of muscle atrophy, further supporting the therapeutic potential of targeting P2X7.</p><p><strong>Conclusions: </strong>The P2X7 receptor contributes to sepsis-induced skeletal muscle atrophy by promoting inflammation and muscle protein degradation through activation of the NLRP3 inflammasome and pyroptosis pathways. Genetic or pharmacological inhibition of P2X7 significantly alleviates muscle damage and functional loss. These findings provide strong experimental evidence supporting P2X7 as a potential therapeutic target for sepsis-associated myopathy.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"491-500"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}