SHOCK最新文献

{"title":"Dual Validation Analysis of Serum CYP3A4 in Predicting NEC in Preterm Infants.","authors":"Xue Liu, Wenqiang Sun, Xiayun Sheng, Jingtao Bian, Yihui Li, Xueping Zhu","doi":"10.1097/SHK.0000000000002590","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002590","url":null,"abstract":"<p><strong>Objective: </strong>Necrotizing enterocolitis (NEC) is a life-threatening condition in premature infants, where timely diagnosis and intervention are crucial. This study investigated the potential of serum CYP3A4 as an early predictive biomarker for NEC and developed a predictive model incorporating CYP3A4.</p><p><strong>Methods: </strong>Bioinformatics analyses were performed to assess the association between CYP3A4 and NEC. Serum samples were collected from preterm infants with a gestational age of less than 32 weeks, born between January 2023 and December 2024. The cohort included 34 infants with NEC and 34 without NEC. Serum CYP3A4 levels were measured using ELISA, and clinical characteristics of NEC infants were analyzed using machine learning to identify predictive factors. A multivariate logistic regression model was constructed and evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA).</p><p><strong>Results: </strong>Serum CYP3A4 levels were significantly higher in NEC infants and were positively associated with disease severity (P < 0.05). CYP3A4 demonstrated positive correlations with inflammatory markers, including C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR), indicating its potential role in the inflammatory cascade and intestinal barrier disruption. In the predictive model, CYP3A4 emerged as a key variable, achieving an area under the ROC curve (AUC) of 0.877, reflecting strong predictive accuracy. Calibration plots and DCA confirmed the model's reliability and clinical utility.</p><p><strong>Conclusion: </strong>Serum CYP3A4 is a promising biomarker for the early diagnosis of NEC, and the prediction model demonstrates robust performance. Future multicenter studies are warranted to validate its consistency and elucidate the underlying mechanisms.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812257","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":"Associations Between Heart Rate Variability and Need for Lifesaving Intervention in a Large Helicopter EMS Service.","authors":"Dylan A Defilippi, David D Salcido, Chase Zikmund, Leonard S Weiss, Aaron C Weidman, Francis X Guyette, Ronald Poropatich, Michael R Pinsky","doi":"10.1097/SHK.0000000000002597","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002597","url":null,"abstract":"<p><strong>Background: </strong>Heart rate variability (HRV) measures give insight into the autonomic regulation of cardiac function in healthy and critically ill patients. The ease and predictive potential of HRV measures may be valuable in optimizing prehospital triage. In this retrospective study, we hypothesized that HRV measures, specifically sample entropy, measured early in emergency transport would predict the need for a prehospital lifesaving intervention (LSI) in a large, heterogenous cohort of critically ill patients.</p><p><strong>Methods: </strong>We obtained patient records from a large helicopter critical care transport service. Continuous electrocardiogram (ECG) data were processed and screened for signal artifacts. Time, frequency, and complexity domain HRV measures were calculated and averaged. Multivariable logistic regression models and t-tests were constructed to establish associations between selected HRV measures and the need for a prehospital LSI, adjusting for demography and case characteristics including patient age, sex, scene run, and trauma/non-trauma. A suite of machine learning algorithms was applied to optimize prediction of outcome measures.</p><p><strong>Results: </strong>A total of 4,521 cases were included for analysis. Of all patients, 68.8% of patients received prehospital LSI. Sample entropy, as well as other HRV measures, was associated with reception of prehospital LSI (OR 0.50 (95% CI [0.43,0.59])). Gradient boosting and random forest algorithms showed the best performance in predicting LSI (AUROC scores = 0.78 - 0.79).</p><p><strong>Conclusions: </strong>Certain HRV measures are associated with prehospital LSI. Subsequent studies should focus on clinical utility and actionable thresholds for triage and initiation of LSIs.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812255","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":"INFORMING INTENSIVE CARE UNIT DIGITAL TWINS: DYNAMIC ASSESSMENT OF CARDIORESPIRATORY FAILURE TRAJECTORIES IN PATIENTS WITH SEPSIS.","authors":"Grace Yao Hou, Amos Lal, Phillip J Schulte, Yue Dong, Oguz Kilickaya, Ognjen Gajic, Xiang Zhong","doi":"10.1097/SHK.0000000000002536","DOIUrl":"10.1097/SHK.0000000000002536","url":null,"abstract":"<p><strong>Abstract: </strong>Understanding clinical trajectories of sepsis patients is crucial for prognostication, resource planning, and to inform digital twin models of critical illness. This study aims to identify common clinical trajectories based on dynamic assessment of cardiorespiratory support using a validated electronic health record data that covers retrospective cohort of 19,177 patients with sepsis admitted to intensive care units (ICUs) of Mayo Clinic Hospitals over 8-year period. Patient trajectories were modeled from ICU admission up to 14 days using an unsupervised machine learning two-stage clustering method based on cardiorespiratory support in ICU and hospital discharge status. Of 19,177 patients, 42% were female with a median age of 65 (interquartile range [IQR], 55-76) years, The Acute Physiology, Age, and Chronic Health Evaluation III score of 70 (IQR, 56-87), hospital length of stay (LOS) of 7 (IQR, 4-12) days, and ICU LOS of 2 (IQR, 1-4) days. Four distinct trajectories were identified: fast recovery (27% with a mortality rate of 3.5% and median hospital LOS of 3 (IQR, 2-15) days), slow recovery (62% with a mortality rate of 3.6% and hospital LOS of 8 (IQR, 6-13) days), fast decline (4% with a mortality rate of 99.7% and hospital LOS of 1 (IQR, 0-1) day), and delayed decline (7% with a mortality rate of 97.9% and hospital LOS of 5 (IQR, 3-8) days). Distinct trajectories remained robust and were distinguished by Charlson Comorbidity Index, The Acute Physiology, Age, and Chronic Health Evaluation III scores, as well as day 1 and day 3 SOFA ( P < 0.001 ANOVA). These findings provide a foundation for developing prediction models and digital twin decision support tools, improving both shared decision making and resource planning.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"573-578"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029344","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":"Construction and Validation of a Risk Assessment Model for Sepsis-Associated Acute Lung Injury in Patients with Sepsis in the Intensive Care Unit.","authors":"Lulu Weng, Haidong Li, Jiawen Shi, Li Zhong","doi":"10.1097/SHK.0000000000002591","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002591","url":null,"abstract":"<p><strong>Purpose: </strong>Sepsis-Associated Acute Lung Injury (SALI) represents a severe complication in sepsis patients, leading to poor clinical outcomes and increased mortality. This study aimed to develop and validate a reliable nomogram for early prediction of SALI in adult critically ill patients, addressing the critical need for timely risk stratification and intervention.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted involving 345 intensive care unit (ICU) sepsis patients from the First People's Hospital of Huzhou. Patients were randomly divided into training (n = 241) and validation (n = 104) cohorts. Multivariate logistic regression and LASSO regression were employed to identify independent risk factors and construct a predictive nomogram.</p><p><strong>Results: </strong>Four independent risk factors were identified: PaCO2, PaO2, serum uric acid (SUA), and SOFA score. The developed nomogram demonstrated excellent discriminative performance, with area under the receiver operating characteristic curve (AUC) of 0.916 in the training cohort and 0.931 in the validation cohort. Calibration curves, decision curve, and SHapley Additive exPlanations (SHAP) analysis confirmed the model's robust predictive performance and clinical utility.</p><p><strong>Conclusions: </strong>The novel nomogram provides a practical, visualized risk assessment tool for early SALI recognition, potentially improving patient outcomes through enhanced understanding and timely interventions in critically ill patients.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812256","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":"COMPLICATED CARDIAC ARREST AND ITS RESUSCITATION CHARACTERISTICS IN PATIENTS WITH INTRACEREBRAL HEMORRHAGE: CHINESE STROKE CENTER ALLIANCE.","authors":"Ping Lu, Lingyun Cui, Hongqiu Gu, Zixiao Li, Yi Ju, Yongjun Wang, Xingquan Zhao, Wenjuan Wang","doi":"10.1097/SHK.0000000000002486","DOIUrl":"10.1097/SHK.0000000000002486","url":null,"abstract":"<p><strong>Abstract: </strong>Objective: Cardiac arrest (CA) is one of the most severe complications in patients with intracerebral hemorrhage (ICH), increasing the risk of death. This study explored the factors influencing CA occurrence and its resuscitation characteristics in ICH patients. Methods: Data were retrieved from the Chinese Stroke Center Alliance database. The primary outcome was CA, and the secondary outcomes were in-hospital death and survival post- CA. Absolute standardized and rate differences were utilized for intergroup comparisons, while logistic regression was employed for correlation analysis. Results: A total of 85,105 patients were enrolled in this study. Among them, 1651 (1.9%) patients experienced CA, of whom 1032 (62.5%) died in hospital. At baseline, prehospital notification from the emergency medical service system was a co-factor influencing CA occurrence and the presence of a death outcome (OR: 1.71, 95% CI: 1.47-1.98, P < 0.001; OR: 0.50, 95% CI: 0.41-0.62, P < 0.001). In terms of complications, posthospital hematoma expansion and swallowing dysfunction were co-factors influencing CA occurrence and the presence of a death outcome (OR: 3.78, 95% CI: 3.20-4.47, P < 0.001, OR: 1.39, 95% CI: 1.11-1.76; P < 0.001; OR: 7.66, 95% CI: 5.48-10.70, P < 0.001, OR: 1.66, 95% CI: 1.08-2.57, P < 0.001). The incidence of CA in ICH patients decreased annually from 2015 to 2019, while survival after CA increased annually ( P < 0.001). Conclusions: Prehospital notification from the emergency medical service system, posthospital hematoma expansion, and swallowing dysfunction were identified as co-factors contributing to CA occurrence and post-CA mortality following ICH. The proportion of CA patients following ICH decreased, while survival rates improved annually from 2015 to 2019.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"552-558"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507118","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":"DYSREGULATED CLOT MECHANICS AND KINETICS IMPACTED BY INJURY SEVERITY, PREDICT MORTALITY AFTER TRAUMA.","authors":"Andrew R Gosselin, Christopher G Bargoud, Abhishek Sawalkar, Shane Mathew, Ashley Toussaint, Matthew Greenen, Susette M Coyle, Marie Macor, Anandi Krishnan, Julie Goswami, Joseph S Hanna, Valerie Tutwiler","doi":"10.1097/SHK.0000000000002544","DOIUrl":"10.1097/SHK.0000000000002544","url":null,"abstract":"<p><strong>Abstract: </strong>Introduction: Coagulopathy following traumatic injury impairs stable blood clot formation and exacerbates mortality from hemorrhage. Understanding how these alterations impact blood clot stability is critical to improving resuscitation. Furthermore, the incorporation of machine learning algorithms to assess clinical markers, coagulation assays, and biochemical assays allows us to define the contributions of these factors to mortality. In this study, we aimed to quantify changes in clot formation and mechanics after traumatic injury and their correlation to mortality. Materials and Methods: Plasma was isolated from injured patients upon arrival to the emergency department prior to blood product administration, or procedural intervention. Coagulation kinetics and mechanics of healthy donors and patient plasma were compared with rheological, turbidity and thrombin generation assays. ELISA's were performed to determine tissue plasminogen activator and D-dimer concentration. Recursive elimination with random forest models were used to assess the predictive strength of clinical and laboratory factors. Results: Sixty-three patients were included in the study. Median injury severity score was 17, median age was 38 years, and mortality was 30%. Trauma patients exhibited reduced clot stiffness, increased fibrinolysis, and reduced thrombin generation compared to healthy donors. Deceased patients exhibited the greatest deviation from healthy levels. Fibrinogen, clot stiffness, D-dimer, and tissue plasminogen activator all demonstrated significant correlation to injury severity score. Machine-learning algorithms identified the importance of coagulation kinetics and clot structure on patient outcomes. Conclusions: Rheological markers of coagulopathy and biochemical factors are associated with injury severity and are highly predictive of mortality after trauma, providing evidence for integrated predictive models and therapeutic strategies.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"587-596"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029340","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":"USP33 PROMOTES CERULEIN-INDUCED APOPTOTIC, OXIDATIVE, AND INFLAMMATORY INJURIES IN ACUTE PANCREATITIS BY DEUBIQUITINATING TRAF3.","authors":"Jian Guo, Huiheng Qu, Peng Cui, Yu Xue","doi":"10.1097/SHK.0000000000002514","DOIUrl":"10.1097/SHK.0000000000002514","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Tumor necrosis factor receptor associated factor 3 (TRAF3) and deubiquitinating enzyme ubiquitin-specific protease 33 (USP33) have been identified to play important roles in inflammatory diseases, including acute pancreatitis (AP). Here, we aimed to explore whether USP33 affected AP progression by affecting TRAF3 expression through deubiquitination. Methods: Cerulein-treated HPDE6-C7 cells were used to mimic AP conditions in vitro . Levels of mRNAs and proteins were examined by qRT-PCR and western blot. Cell proliferation and apoptosis were evaluated using CCK-8 assay, EdU assay, and flow cytometry. Cell oxidative stress was assessed by detecting the production of superoxide dismutase and malonaldehyde. ELISA analysis detected IL-6 and TNF-α levels. Macrophage M1 polarization was evaluated by flow cytometry. Cellular ubiquitination analyzed the ubiquitination effect on TRAF3. Protein interaction between USP33 and TRAF3 was identified by immunofluorescence staining. Results: Cerulein dose-dependently induced apoptosis, oxidative stress, and inflammatory response in HPDE6-C7 cells and promoted macrophage M1 polarization to enhance inflammation ( P < 0.05). TRAF3 was highly expressed in AP patients (3.5±1.10 vs. 1.0 ±0.74, P < 0.05) and cerulein-induced HPDE6-C7 cells (3.3 ±0.34 vs. 1.0 ±0.10, P < 0.05). Knockdown of TRAF3 protected HPDE6-C7 cells from cerulein-induced apoptotic, oxidative and inflammatory injuries. Mechanistically, USP33 interacted with TRAF3 and induced TRAF3 deubiquitination to upregulate its expression ( P < 0.05). Further analyses showed that USP33 knockdown reversed cerulein-induced apoptosis, oxidative stress and inflammation in HPDE6-C7 cells by TRAF3 ( P < 0.05). Moreover, USP33-TRAF3 activated the NF-κB pathway ( P < 0.05). Conclusion: USP33 promoted cerulein-induced apoptosis, oxidative stress and inflammation in pancreatic ductal cells by deubiquitinating TRAF3, indicating a novel insight into the pathogenesis of AP.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"559-565"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787036","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":"THE CAUSAL ASSOCIATION OF CARDIOMETABOLIC DISEASES AND SEPSIS-RELATED OUTCOMES: A MENDELIAN RANDOMIZATION AND POPULATION STUDY.","authors":"Mengmeng Qi, Jin Wei, Meng Zhang, Chucheng Jiao, Chang He, Liutao Sui, Shiyin Ma, Zhi Mao, Xudong Pan, Xiaoyan Zhu","doi":"10.1097/SHK.0000000000002538","DOIUrl":"10.1097/SHK.0000000000002538","url":null,"abstract":"<p><strong>Abstract: </strong>Objective: The causality between cardiometabolic disease (CMD) and sepsis has remained largely unknown. To elucidate this, we conducted a Mendelian randomization (MR) and population study. Methods: First, we used univariable and multivariable MR analyses to investigate causal associations between CMD and sepsis-related outcomes. We obtained genome-wide association study summary from both the MRC Integrative Epidemiology Unit and the FinnGen consortium. Subsequently, a two-step mediation MR analysis was performed to explore mediators. Afterward, we conducted an observational study using the Medical Information Mart for Intensive Care IV database, in which multivariable logistic regression models were utilized to examine the relationship between CMD and sepsis-related outcomes. Results: In the MR study, type 2 diabetes mellitus (OR = 1.058, 95% CI = 1.017-1.100, P = 0.005), obesity (OR = 1.113, 95% CI = 1.057-1.172, P < 0.001), and heart failure (HF) (OR = 1.178, 95% CI = 1.063-1.305, P = 0.002) were independently causally related to sepsis. Obesity (OR = 1.215, 95% CI = 1.027-1.437, P = 0.023) and HF (OR = 1.494, 95% CI = 1.080-2.065, P = 0.015) also showed independent causal associations with sepsis critical care admission. Mediation MR analysis identified 23 blood metabolites potentially causally linked to sepsis ( P < 0.05), yet none mediated the relationship between CMD and sepsis. In the observational study, we found associations between sepsis and several conditions including type 2 diabetes mellitus, obesity, hypertension, stroke, HF, and hyperlipidemia after adjusting for confounding factors. Moreover, hypertension, stroke, HF, coronary artery disease, and hyperlipidemia were linked to sepsis critical care admission. Conclusion: This study has, for the first time, revealed indicative evidence of a causal relationship between CMD and sepsis through observational and genetic evidence. Taken together, clinical attention to sepsis may be warranted among patients with CMD.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"579-586"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450095","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":"THE INTERACTION BETWEEN ANTITHROMBIN AND ENDOTHELIAL HEPARAN SULFATE MITIGATES PULMONARY THROMBOINFLAMMATION AFTER TRAUMA AND HEMORRHAGIC SHOCK.","authors":"Maria Del Pilar Huby Vidaurre, Ava K Mokhtari, Baron K Osborn, Bryan A Cotton, Yao-Wei Wang, Yongmei Xu, Katelyn Arnold, Jian Liu, Jillian R Richter, Jessica C Cardenas","doi":"10.1097/SHK.0000000000002543","DOIUrl":"10.1097/SHK.0000000000002543","url":null,"abstract":"<p><strong>Abstract: </strong>Introduction : Trauma and hemorrhagic shock (T/HS) are associated with multiple organ injury. Antithrombin (AT) has anti-inflammatory and organ protective activity through its interaction with endothelial heparan sulfate containing a 3- O -sulfate modification. Our objective was to examine the effects of T/HS on 3- O -sulfated (3-OS) heparan sulfate expression and determine whether AT-heparan sulfate interactions are necessary for its anti-inflammatory properties. Methods : Male Sprague-Dawley rats underwent laparotomy, gut distension and fixed-pressure hemorrhagic shock (HS) and resuscitation. Liquid chromatography-coupled mass spectrometry analyses were performed to measure pulmonary and plasma heparan sulfate di/tetrasaccharides. Pulmonary mRNA levels were assessed by nCounter panel. Rats were treated with vehicle or surfen (1 mg/kg), a small molecule heparan sulfate antagonist, to block the interaction between AT and endothelial cells prior to T/HS and resuscitated with fresh frozen plasma (FFP), lactated Ringer's (LR), or AT-supplemented LR. Lung injury was assessed histologically for injury and fibrin deposition and immunostained for myeloperoxidase (MPO). Plasma was assessed for circulating inflammatory biomarkers. Results: T/HS significantly reduced pulmonary expression of 6- O and 3- O sulfated heparan sulfate, which was associated with reduced pulmonary 6- O - and 3- O -sulfotransferase mRNA levels. Surfen increased fibrin deposition and inflammatory cell infiltration into pulmonary tissue in T/HS rats resuscitated with FFP but had no effect in LR resuscitated rats. Although T/HS and LR resuscitation worsened histologic lung injury compared to sham, regardless of surfen treatment, lung injury was notably improved in FFP-resuscitated rodents pretreated with vehicle but not surfen. Surfen abrogated the anti-inflammatory effects of FFP, indicated by notable increases in circulating levels of multiple proinflammatory mediators compared to rats pretreated with vehicle. Finally, we observed significant increases in pulmonary fibrin and MPO staining in rats pretreated with surfen followed by resuscitation with LR supplemented with AT compared to vehicle, which was associated with notable increases in lung injury scores. Conclusions: T/HS causes pronounced reductions in pulmonary expression of 3-OS heparan sulfate, which is essential to AT's antithrombotic and anti-inflammatory activity. Blocking the interaction between AT and the endothelium attenuates the antithromboinflammatory and organ protective properties of FFP, suggesting that AT-endothelial anticoagulant function and anti-inflammatory signaling is important for organ protection during T/HS.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"638-647"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029350","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":"GASTRODIN PROTECTS AGAINST SEPSIS-ASSOCIATED ENCEPHALOPATHY BY SUPPRESSING FERROPTOSIS.","authors":"Yunfei Xu, Jing Chen, Lin Zhou, Yao Zhao, Nina He, Qing Xu, Jie Zhao, Ying Liu","doi":"10.1097/SHK.0000000000002542","DOIUrl":"10.1097/SHK.0000000000002542","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Sepsis-associated encephalopathy (SAE) represents a severe complication of sepsis, substantially elevating both mortality and healthcare costs for patients. Gastrodin (GAS), a principal bioactive constituent of Gastrodia elata Blume, is neuroprotective in various neurological disorders, including ischemic stroke, epilepsy, Alzheimer's disease, and neuropathic pain. In this study, we sought to investigate whether GAS could serve as a protective agent against SAE. Methods: Mice were subjected to cecal ligation and puncture (CLP) or the murine brain microvascular endothelial cell bEnd.3 was exposed to lipopolysaccharide (LPS) and subsequently treated with GAS. We assessed neurological deficits, blood-brain barrier (BBB) integrity, neuroinflammation, and the state of ferroptosis to evaluate the regulation of GAS on SAE. Mechanistically, we utilized glutathione peroxidase 4 (GPX4) knockout mice to delineate the crucial role of GPX4 and examined the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway to uncover the upstream signaling of GPX4. Results: GAS mitigated neurological deficits in SAE mice and reduced BBB disruption and neuroinflammation both in vivo and in vitro . Functionally, the neuroprotective effects of GAS were realized through the inhibition of ferroptosis. Furthermore, we demonstrated that GPX4 played a pivotal role in this process. Lastly, we found that the COX-2/PGE2 pathway was activated following GAS treatment in SAE mice, thereby increasing the expression level of GPX4. Conclusions: Our study elucidated that GAS offers protection against SAE by suppressing ferroptosis through the activation of the COX-2/PGE2/GPX4 axis. This research validates the therapeutic potential of GAS and provides novel insights into potential therapeutic strategies for the management of SAE.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"628-637"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922343","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}