SHOCK最新文献

{"title":"Immunological and histopathological features of secondary injury in a long-term mouse model of persistent inflammation, immunosuppression, and catabolism syndrome.","authors":"Takumi Tsuchida, Takeshi Wada, Asumi Mizugaki, Yoshitaka Oda, Katsuhide Kayano, Kazuma Yamakawa, Shinya Tanaka","doi":"10.1097/SHK.0000000000002917","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002917","url":null,"abstract":"<p><p>Persistent inflammation, immunosuppression, and catabolism syndrome (PIICS) is a major cause of prolonged morbidity and poor outcomes among critical illness survivors. We established long-term murine PIICS models using two peritonitis-induced sepsis methods-cecal ligation and puncture (CLP) and fecal suspension intraperitoneal injection (FSI)-and investigated their immunological and histopathological features over 2 months. Survivors were defined as PIICS model mice, with unoperated mice serving as controls. Following an intraperitoneal lipopolysaccharide (LPS; 10 mg/kg) challenge, 27 plasma cytokines and chemokines were quantified before and 20 h after administration, and survival was monitored for 14 days. Survivors of CLP and FSI exhibited sustained baseline elevations in inflammatory mediators (G-CSF, IL-7, CCL3/4) and reductions in anti-inflammatory cytokines (IL-13, TGF-β2) compared with those in controls. Following the LPS challenge, control mice showed robust cytokine induction, and 4 of 13 died, whereas both PIICS groups exhibited globally suppressed cytokine responses with no mortality (p = 0.011 vs. controls). Histopathological staining showed mild splenic macrophage infiltration at baseline in both PIICS groups. Upon LPS administration, pulmonary congestion, splenic macrophage infiltration, and neutrophil infiltration into the portal vein were observed. Intra-abdominal abscesses or granuloma-like masses occurred in 50% of CLP-PIICS mice. Collectively, these long-term PIICS models recapitulate key clinical features, including persistent dysregulated inflammation, impaired responsiveness to secondary stimuli, and chronic tissue pathology, providing a platform to investigate the transition from acute sepsis to PIICS and for preclinical testing of immune-restorative or metabolic interventions in survivors of sepsis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797779","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":"miR-15a-3p promotes excessive autophagy and drives skeletal muscle atrophy in sepsis.","authors":"Ling-Ling Zhou, Shu-Li Zhang, Wei-Qing Xiao, Xiao-Yong Zhang, Xiao-Yan Zhu, Peng-Xiang Wang, Yu-Jian Liu","doi":"10.1097/SHK.0000000000002924","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002924","url":null,"abstract":"<p><p>Approximately 50% of sepsis patients develop acute skeletal muscle atrophy and dysfunction. Autophagy plays an important role in skeletal muscle atrophy and dysfunction, and skeletal muscle autophagy is known to be regulated by multiple miRNAs. In this study, we found that miR-15a-3p was significantly upregulated in published Gene Expression Omnibus (GEO) datasets of septic patients and septic mouse skeletal muscle. Correlation analysis revealed that miR-15a-3p was associated with autophagy activation in septic patients and septic mouse skeletal muscle. Inhibition of miR-15a-3p attenuated excessive autophagy and ameliorated skeletal muscle atrophy in septic mice and differentiated C2C12 myotubes. Overexpression of miR-15a-3p increased autophagy and skeletal muscle atrophy in mice and differentiated C2C12 myotubes. Furthermore, we identified peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) as a direct target of miR-15a-3p. Our findings elucidate the molecular mechanisms underlying miR-15a-3p in sepsis-induced autophagy and skeletal muscle injury, highlighting its potential as a therapeutic target.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797799","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":"Severe Burn Injury as a Chronic Immunometabolic Disease.","authors":"Thomas O Vogler, Kiran U Dyamenahalli, Scott W Mueller, Arek J Wiktor, Rachel H McMahan, Alexandra E Halevi, Elizabeth J Kovacs","doi":"10.1097/SHK.0000000000002926","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002926","url":null,"abstract":"<p><p>Over the past five decades, advances in acute burn care have markedly improved early survival following severe thermal injury. However, long-term epidemiologic studies demonstrate that burn survivors remain at increased risk for metabolic disease, cardiovascular pathology, malignancy, cognitive impairment, and accelerated aging, well beyond wound closure. These observations suggest that severe burn injury can initiate a chronic disease state characterized by persistent physiologic dysregulation in a subset of patients. Emerging evidence indicates that this phenotype is driven by sustained immunometabolic dysfunction, in which immune and metabolic pathways are tightly coupled and mutually reinforcing. Severe burn injury induces durable reprogramming of innate and adaptive immune cells alongside prolonged hypermetabolism, mitochondrial dysfunction, and neuroendocrine stress signaling. This results in a persistent inflammatory, immunosuppressed, catabolic syndrome (PIICS), where chronic inflammation coexists with impaired adaptive immunity and ongoing amino acid depletion. In this review, we synthesize population-based, clinical, and experimental data supporting burn injury as a chronic immunometabolic disease. We highlight key mechanisms linking immune dysfunction with altered substrate utilization, mitochondrial bioenergetics, and neuroimmune signaling, and discuss how these pathways contribute to long-term organ dysfunction. Finally, we outline emerging opportunities for risk stratification and therapeutic interventions targeting integrated immunometabolic pathways.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797786","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":"IL1R2⁺ Inflammatory Monocytes Contribute to Immune Dysregulation and Predict Mortality in COVID-19.","authors":"Yiying Yang, Fang Yu, Muyuan Li, Hao Ma, Huali Zhang, Xianzhong Xiao, Liqin Cheng","doi":"10.1097/SHK.0000000000002919","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002919","url":null,"abstract":"<p><strong>Background: </strong>Coronavirus disease 2019 (COVID-19) is characterized by dysregulated immune responses and excessive inflammation, contributing to severe disease and mortality. Interleukin-1 receptor type 2 (IL1R2), a decoy receptor for interleukin-1 (IL-1), regulates inflammatory responses; however, its cellular distribution and clinical significance in COVID-19 remain unclear.</p><p><strong>Methods: </strong>Publicly available single-cell RNA sequencing (scRNA-seq) dataset (GSE149689) of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients were analyzed. An independent monocyte transcriptomic dataset (GSE198256) was analyzed to evaluate IL1R2 dynamics during COVID-19 and recovery. Differential expression, functional enrichment, regulon activity, and CellChat analyses were performed to characterize IL1R2⁺ monocytes. Serum IL1R2 levels were measured in COVID-19 patients and healthy controls (HCs), and their associations with disease severity and mortality were evaluated.</p><p><strong>Results: </strong>Single-cell analysis revealed that IL1R2 was predominantly expressed in monocytes from COVID-19 patients. IL1R2 expression was increased during active COVID-19 and decreased after recovery. IL1R2⁺ monocytes exhibited enhanced inflammatory transcriptional programs, increased activity of inflammation-associated regulons, and activation of TNFα/NF-κB, interferon, and IL6-JAK-STAT3 pathways. Cell-cell communication analysis identified IL1R2⁺ monocytes as active mediators of CCL, CXCL, IL1, and TNF signaling networks. Serum IL1R2 levels were elevated in COVID-19 patients, further increased in non-survivors, and correlated with inflammatory markers, tissue injury indicators, and coagulation abnormalities. IL1R2 showed predictive performance for mortality comparable to procalcitonin and D-dimer.</p><p><strong>Conclusions: </strong>IL1R2 identifies a highly inflammatory monocyte state associated with COVID-19 immune dysregulation. Elevated IL1R2 levels reflect disease activity and poor outcomes, supporting its potential role as a complementary prognostic biomarker and therapeutic target.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713668","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 Heparin Initiation Is Associated With Improved Outcomes in Sepsis‑Induced Myocardial Injury: A Target Trial Emulation and Experimental Study.","authors":"Xiaofei Yin, Xuyang Ji, Zhen Yu, Ruochuan Li, Hao Zhang, Shuxing Wei, Yiming Dong, Yuguo Chen","doi":"10.1097/SHK.0000000000002922","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002922","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of heparin therapy in sepsis remains uncertain.</p><p><strong>Objective: </strong>To investigate the association between early heparin use and outcomes in patients with sepsis-induced myocardial injury (SIMI) and to explore potential cardioprotective mechanisms in experimental models.</p><p><strong>Methods: </strong>The present study employed a target trial emulation (TTE) using data from the MIMIC-IV database to investigate intensive care unit (ICU) patients with SIMI. The cloning-censoring-weighting (CCW) method was used to address immortal time bias. Early heparin use was defined as administration within 72 h of ICU admission. Weighted Cox proportional hazards models were applied to assess its association with 28-day, 90-day, and 365-day all-cause mortality, with sensitivity analyses conducted in the propensity score-matched (PSM) cohort. In parallel, murine SIMI models induced by lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) were used to explore the potential cardioprotective effects of heparin.</p><p><strong>Results: </strong>A total of 2,550 patients with SIMI were included. In the TTE analysis, early heparin initiation was associated with lower 28-day mortality (hazard ratio [HR] = 0.786, 95% confidence interval [CI]: 0.700-0.883, P < 0.001), 90-day mortality (HR = 0.768, 95% CI: 0.691-0.854, P < 0.001), and 365-day mortality (HR = 0.789, 95% CI: 0.715-0.870, P < 0.001). In experimental models, heparin treatment significantly attenuated myocardial injury and improved survival.</p><p><strong>Conclusions: </strong>Early heparin use was associated with reduced mortality in patients with SIMI, while experimental studies suggested potential cardioprotective effects in septic mice.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070038","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":"Association Between the Sequential Organ Failure Assessment-2 (SOFA-2) Score and 90-Day and 365-Day Mortality in Patients With Sepsis: A Retrospective Cohort Study Based on the MIMIC-IV Database.","authors":"Zhengchao Li, Yuzhu Wang, Yudong Gao, Yulin Tian, Fenggao Zhou, Xu Cheng, Bing Gong, Dexing Yang","doi":"10.1097/SHK.0000000000002918","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002918","url":null,"abstract":"<p><strong>Background: </strong>The Sequential Organ Failure Assessment-2 (SOFA-2) score is a recently developed update of the conventional SOFA score that incorporates contemporary patterns of organ support in the intensive care unit (ICU). However, the association between SOFA-2 and long-term mortality in patients with sepsis has not been well characterized.</p><p><strong>Methods: </strong>This retrospective cohort study extracted adult sepsis ICU data from MIMIC-IV v3.1. ICU admission SOFA-2 scores (0-24) were calculated. Boruta algorithm selected confounders; binary logistic regression and restricted cubic splines (RCS) analyzed linear association between SOFA-2 and 90-/365-day all-cause mortality. Random forest (RF) combined key predictors, SHAP interpreted feature importance, and AUC evaluated discriminative performance.</p><p><strong>Results: </strong>8,779 patients were enrolled. Fully adjusted regression showed SOFA-2 independently elevated 90-day mortality (OR=1.17, 95%CI 1.15-1.18) and 365-day mortality (OR=1.16, 95%CI 1.14-1.18). RCS confirmed an approximately linear correlation (all nonlinearity p>0.05). Single SOFA-2 yielded modest AUCs: 0.65 (90-day) and 0.64 (365-day). The RF model improved prediction (validation AUC: 0.68 for 90-day, 0.67 for 365-day). SHAP analysis identified SOFA-2 as the most influential predictor.</p><p><strong>Conclusions: </strong>SOFA-2 provides moderate, stable long-term mortality discrimination for sepsis patients. Further external validation and optimization are required to improve its risk stratification utility.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689838","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":"Sex-Based Differences in Severe Trauma and Hemorrhagic Shock: A Systematic Review of Pre-Clinical and Veterinary Animal Studies.","authors":"Gennadi Saiko, Fazle Kibria, Denis Bragin","doi":"10.1097/SHK.0000000000002920","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002920","url":null,"abstract":"<p><strong>Purpose: </strong>To systematically review preclinical studies to determine whether biological sex alters outcomes after severe trauma with hemorrhagic shock (T/HS), identify the mechanistic drivers of any sex dimorphism, and define key gaps that limit translation to critical care.</p><p><strong>Methods: </strong>Following PRISMA guidance, we searched PubMed and Google Scholar through December 2025 for original animal or veterinary T/HS studies, comparing biological sexes or manipulating sex hormones. Exclusions included non-hemorrhagic shock, traumatic brain injury, and reviews. Two reviewers independently screened 1,450 records and assessed risk of bias via SYRCLE. Data were extracted on species, hormonal status, survival, organ function, and mechanisms. A structured narrative synthesis was performed as study heterogeneity precluded quantitative meta-analysis.</p><p><strong>Results: </strong>Of the 1,450 records, 66 met the inclusion criteria. In rodents, females, particularly during proestrus, exhibited superior survival, preserved organ function, and reduced inflammation. These advantages were typically reversed by ovariectomy and mimicked by estrogen or ER-β agonists. Conversely, male vulnerability was linked to androgen-driven immune dysfunction and mitigated by castration or flutamide. Age and sepsis often reverse female benefits. Emerging research highlighted non-classical pathways, such as autophagy and pyroptosis. High model heterogeneity and reporting gaps precluded meta-analysis.</p><p><strong>Conclusion: </strong>Preclinical evidence confirms sex-dependent resilience in T/HS, primarily driven by sex steroids and immune-vascular modulation. To bridge the translational gap, clinical studies should adopt sex-stratified analyses and prospectively record hormonal status. Future preclinical research must prioritize standardized reporting and the use of large-animal or uncontrolled hemorrhage models to validate these findings for critical care.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702042","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":"Phenotyping Sepsis at Emergency Department Presentation Using Early Clinical Data: A Multicenter Cohort Study.","authors":"Junhyuk Seo, Namkee Oh, Gee Young Suh, Chae-Man Lim, Won Chul Cha, Ryoung-Eun Ko","doi":"10.1097/SHK.0000000000002921","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002921","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is heterogeneous, and early emergency department (ED) management is constrained by limited information and dynamic clinical trajectories.</p><p><strong>Methods: </strong>Using the nationwide Korean Sepsis Alliance (KSA) registry, we applied k-means clustering to nine routine ED variables (demographics, vital signs, Clinical Frailty Scale, mental status, lactate). The model was developed in KSA 3 (2019-2021) and tested for temporal reproducibility in the independent KSA 5 cohort (2022-2023). Phenotypes were compared on 7-day mortality, early sepsis-bundle compliance, and SOFA trajectories; stability was assessed by bootstrap resampling and alternative clustering. One-hour vasopressor non-compliance was decomposed into criterion-not-met versus delivered-with-delay.</p><p><strong>Results: </strong>Six phenotypes were identified in 9,430 patients and reproduced in 7,184 (mortality-rank ρ = 1.00; calibration drift, O/E 0.83-1.32). Seven-day mortality ranged 6.7%-31.8%. Extreme-severity phenotypes (A, F, E) were bootstrap-robust (Jaccard 0.65-0.91), whereas intermediate phenotypes (B, D) were less stable (0.21-0.47), consistent with a continuous severity spectrum. Non-compliance composition separated phenotypes that severity scores rank together: predominantly criterion-not-met (appropriate withholding) in low-acuity phenotype C versus delivered-with-delay in high-acuity phenotype E. Phenotypes B and F, matched on presenting physiology and mortality but differing in frailty and mental status, still differed in composition (criterion-not-met 49.6% vs 28.3%; p < 0.001). SOFA trajectories were highest in phenotype E.</p><p><strong>Conclusions: </strong>ED-presentation phenotyping using routine variables identifies six cross-sectional signatures along the sepsis severity spectrum rather than definitive subtypes. Decomposing bundle non-compliance shows that it combines appropriate withholding and urgency-associated delay in phenotype-dependent proportions, a distinction one-dimensional severity scores cannot make, relevant to phenotype-stratified resuscitation warranting prospective evaluation.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702075","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":"Mesenchymal Stem Cell-Derived Extracellular Vesicles Mitigate Immune Cell Activation in an in Vitro Model of Postresuscitation Inflammation.","authors":"Tyler J Rolland, Sumbule Zahra, Luke A Graser, Daniel Cucinotta, Rebeccah Young, Brian R Weil","doi":"10.1097/SHK.0000000000002853","DOIUrl":"10.1097/SHK.0000000000002853","url":null,"abstract":"<p><strong>Background: </strong>Systemic inflammation is a key component of postcardiac arrest syndrome (PCAS) and contributes to significant morbidity and mortality after resuscitation from sudden cardiac arrest. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as promising immunomodulatory agents in various inflammatory conditions, including ischemia-reperfusion injury (IRI). We investigated the therapeutic potential of MSC-EVs in porcine peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharide (LPS) or mitochondrial DNA (mtDNA) to model immune cell activation relevant to PCAS.</p><p><strong>Methods: </strong>Transcriptomic profiling was performed on PBMCs from swine at baseline and 4 hours after resuscitation from cardiac arrest and compared with ex vivo mtDNA-stimulated PBMCs to establish mtDNA as a PCAS-relevant pro-inflammatory stimulus. PBMCs from healthy pigs were then stimulated with 1 μg/mL mtDNA + transfection reagent or 5 μM LPS and treated with escalating concentrations of MSC-EVs. Flow cytometry, quantitative PCR, ELISA, and reactive oxygen/nitrogen species measurements were performed to assess PBMC activation.</p><p><strong>Results: </strong>Transcriptomic profiling identified overlapping differentially expressed genes and convergent enrichment of cytosolic DNA-sensing/antiviral response pathways and cytokine/chemokine signaling programs in mtDNA-stimulated PBMCs and PBMCs collected from swine with PCAS. In mtDNA-stimulated PBMCs, MSC-EVs attenuated dendritic cell activation, reduced inflammatory cytokine gene expression and release, and decreased reactive oxygen/nitrogen species production in a concentration-dependent manner. MSC-EVs also produced concentration-dependent reductions in LPS-induced granulocyte activation and expression of IFNα, IL-1β, and TNFα.</p><p><strong>Conclusions: </strong>MSC-EVs exert immunomodulatory effects against mtDNA- and LPS-mediated PBMC activation, supporting further investigation as a cell-free therapeutic strategy to target immune activation in PCAS and other acute inflammatory conditions.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"538-549"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729782","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":"Pirinixic Acid Protects Against Hemorrhagic Shock by Regulating Neutrophil-Associated Key Genes.","authors":"Xiaowei Zhou, Liyong Zou, Haoyue Deng, Yu Zhu, Jie Zhang, Qinghui Li, Shijie Zhou, Liangming Liu, Li Wang, Tao Li","doi":"10.1097/SHK.0000000000002763","DOIUrl":"10.1097/SHK.0000000000002763","url":null,"abstract":"<p><strong>Background: </strong>The uncontrolled inflammatory cascade triggered by hemorrhagic shock (HS) can exacerbate tissue damage and organ dysfunction. Neutrophils, as the most abundant type of leukocytes, are key mediators of the innate immune response in the early stages of injury. There is a lack of suitable treatments targeting neutrophils in HS.</p><p><strong>Methods: </strong>We used machine learning algorithms to identify neutrophil-associated key genes in patients with HS and assessed the diagnostic efficacy of these genes. Weighted gene co-expression network analysis and consensus clustering analysis were performed based on the key genes to explore their role in HS. Finally, we predicted the binding of key genes to drug candidates using molecular docking and observed the effects of drug candidates and the expression of key genes in animals with HS.</p><p><strong>Results: </strong>We screened for key genes with good diagnostic efficacy (ARG1, F2RL1, MPP1, RHOG, UPP1) that activate JAK-STAT3 signaling and apoptotic signaling, leading to poor prognosis. Pirinixic acid screened by the Comparative Toxicogenomics Database has good affinity with key genes, and it can significantly restore the level of inflammatory factors and coagulation function in HS rats, protect the function of vital organs, and prolong the survival time. It was confirmed that pirinixic acid may improve neutrophil immunity disorders by acting on MPP1, RHOG, and F2RL1, and thus protect against HS.</p><p><strong>Conclusions: </strong>The protective effect of pirinixic acid against HS-induced immune dysregulation is closely associated with the neutrophil genes MPP1, RHOG, and F2RL1.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"560-574"},"PeriodicalIF":2.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13384378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850810","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}