SHOCK最新文献

{"title":"Selenomethionine Attenuates Sepsis-Induced Skeletal Muscle Atrophy by Inhibiting ROS/NLRP3 Signaling.","authors":"Tonghan Li, Xuan Zhao, Zhikai Xu, Fan Yang, Zhanfei Li, Xiangjun Bai, Hao Zhu, Hong Zhao, Yukun Liu, Yuchang Wang","doi":"10.1097/SHK.0000000000002690","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002690","url":null,"abstract":"<p><strong>Objective: </strong>Sepsis-induced muscle atrophy (SIMA) 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.</p><p><strong>Methods: </strong>A murine sepsis model was established via cecal ligation and puncture (CLP), followed by treatment with varying doses of Se-Met. Survival rate, body weight, skeletal muscle mass, and muscle strength were evaluated. Histological analysis (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, IL-1β) were examined via Western blot. In vitro, C2C12 myoblasts were stimulated with lipopolysaccharide (LPS) and treated with Se-Met to assess oxidative stress markers (ROS, MDA, SOD, GSH-Px), pyroptosis-related proteins, and inflammatory cytokines (e.g., IL-6, IL-18). ROS scavenger NAC, NLRP3 agonist, and ROS inducer were employed in mechanistic studies to further elucidate the molecular mechanisms.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081508","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 ferroptosis pathway is required for glycocalyx damage during hemorrhagic shock.","authors":"Aditya Vinjamuri, David Engelhardt, Willard R Covey, Sarah Abdullah, Farhana Shaheen, Zander Gerberg, Sharven Taghavi, Juan Duchesne, Olan Jackson-Weaver","doi":"10.1097/SHK.0000000000002701","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002701","url":null,"abstract":"","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081520","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":"Hemodynamic Changes, Organ Dysfunction, and Clinical Outcomes in Patients with Sepsis-Induced Myocardial Dysfunction.","authors":"Xu-Dong Shen, De-Yu Meng, Yue-Hong Yin, Hua-Sheng Zhang, Dan-Yun Li, Zhi-Wei Li, Hao Guo","doi":"10.1097/SHK.0000000000002696","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002696","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate the hemodynamic changes associated with sepsis-induced myocardial dysfunction (SIMD), assess its impact on organ dysfunction, and evaluate its clinical outcomes.</p><p><strong>Methods: </strong>A cohort of 170 patients with sepsis hospitalized at the First Hospital of Kunming were included and categorized into two groups: Group A (sepsis without myocardial dysfunction, n = 106) and Group B (SIMD, n = 64). The groups were compared with respect to hemodynamic parameters, organ dysfunction, and clinical outcomes.</p><p><strong>Results: </strong>Patients in Group B were older and had higher acute physiology and chronic health evaluation II scores, central venous pressure, and dp/dt max, as well as elevated biomarker levels indicative of myocardial dysfunction, compared to those in Group A. The incidence of multiple organ dysfunction was significantly higher in Group B (all p < 0.05). Additionally, Group B exhibited prolonged mechanical ventilation duration, extended intensive care unit stays, and increased mortality rates. Multivariate analysis identified APACHE II scores (at days 1 and 7), troponin I (TnI), and B-type natriuretic peptide (BNP) as independent risk factors for septic shock in patients with SIMD. BNP demonstrated the highest area under the curve for predicting septic shock in this population, with an optimal cutoff value of 268 pg/mL (sensitivity 71.9%, specificity 80.2%, 95% CI 0.714-0.861).</p><p><strong>Conclusion: </strong>SIMD is associated with significant hemodynamic disturbances, increased respiratory dysfunction, prolonged mechanical ventilation and hospitalization, and elevated mortality. BNP and cTnI levels were significantly elevated in patients with SIMD, indicating a heightened risk of septic shock and multiorgan dysfunction, leading to adverse clinical outcomes.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081550","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":"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":"https://doi.org/10.1097/SHK.0000000000002685","url":null,"abstract":"<p><p>Sepsis and sepsis-induced myocardial dysfunction (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 (LVEF) 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, APACHE II score, SOFA score, MODS, LVEF, lactate (Lac), WBC, PCT, and CRP. Multivariate analysis demonstrated that age, APACHE II score, Lac, 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":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-05","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":"Blood transcriptome analysis reveals CTSB and ATP6V0D1 expression in circulating monocytes as potential biomarkers of sepsis.","authors":"Yaojun Peng, Qiyan Wu, Baimei Zhuang, Xinhuan Ding, Yawen Peng, Di Jing, Maolin Xu, Meng Wang, Yanchao Liang, Bo Pan, Yuyu Liu, Haiyan Zhu","doi":"10.1097/SHK.0000000000002693","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002693","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a dysregulated host response to infections, leading to organ dysfunction and posing a critical threat to human health. Despite tremendous progress in understanding the pathophysiology of sepsis, early diagnosis and clinical treatment efficacy remain unsatisfactory. This study aimed to identify transcriptomic alterations in peripheral blood mononuclear cells (PBMCs) as potential biomarkers of sepsis.</p><p><strong>Methods: </strong>Bulk RNA-seq was performed on PBMCs obtained from 20 patients with sepsis and 12 healthy individuals. Multiple bioinformatics tools were used to identify key genes and signaling pathways associated with sepsis progression. The hub genes were further externally validated by publicly available blood transcriptomic data and experimentally verified by immunocytofluorescence assay.</p><p><strong>Results: </strong>Differential expression analysis revealed 4,522 differentially expressed genes (DEGs) in patients with sepsis (n = 20) compared to healthy individuals (n = 12). Weighted gene co-expression network analysis identified multiple gene modules closely related to sepsis, with the royal blue module exhibiting the most positive correlation with sepsis. Intersection analysis yielded 176 common genes between the royal blue module genes and DEGs. Protein-protein interaction analysis revealed five hub genes (CTSB, CTSD, ATP6V0D1, UBE2D1, and ATP6V0C) associated with sepsis. Immune infiltration was dissected by single sample gene set enrichment analysis, revealing associations between hub genes and monocytes. Single-cell RNA sequencing data analysis and immunocytofluorescence assay confirmed the upregulation of CTSB and ATP6V0D1 in circulating monocytes. Notably, CTSB and ATP6V0D1 were significantly associated with 28-day mortality of sepsis patients in the external validation cohort (n = 479).</p><p><strong>Conclusion: </strong>This study identifies CTSB and ATP6V0D1 expression in circulating monocytes as potential biomarkers and promising therapeutic targets for sepsis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081440","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":"https://doi.org/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 ATP-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 GSDMD, 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>Conclusion: </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":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-05","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}

{"title":"Spices to combat sepsis - Curcumin piperine combination increases survival and modulates immune response in a murine two-hit trauma model.","authors":"Christina Schwenk, Nadja Muehlhaupt, Laura Heimann, Anna Friesen, Li Wan, Peter Biberthaler, Marc Hanschen","doi":"10.1097/SHK.0000000000002691","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002691","url":null,"abstract":"<p><strong>Context: </strong>Following trauma Systemic Inflammatory Response Syndrome (SIRS) and its counterpart the Compensatory Anti-inflammatory Response Syndrome (CARS) interact in a very sensitive balance. CD4+ T regulatory cells (CD4+ Tregs) play a crucial role in this interaction and can have a protective effect. We were able to show a reciprocal activation of CD4+ Tregs and platelets early after trauma. With this study we aimed to investigate the immunomodulatory potential of curcumin + piperine (C+P) or ancrod and to clarify their effect on the survival rate in a long-term two-hit trauma model.</p><p><strong>Methods: </strong>C57BL/6N-mice were subjected to standardized burn injury inducing SIRS, followed by sepsis induction via Cecal Ligation and Puncture (CLP) seven days later. Mice treated with C+P or ancrod were compared to control groups. After CLP, animals received no further sepsis treatment. At a maximum follow-up period of 23 days or upon reaching termination criteria, tissue was collected for pathohistological and immunohistochemical evaluation as well as immunological analysis using (phospho-)flow cytometry and multiplex ELISA.</p><p><strong>Results: </strong>Curcumin + piperine treated mice showed a clear survival advantage (p = 0.0097) with systemic alterations in cytokine levels, e.g. for IL-4 (p = 0.0263) and IL-10 (p = 0.0022). Their total organ damage was comparable to Sham-group. C+P also had a significant effect on extracellular T cell activation markers. CD8+ T cells showed lower MHC II (MFI = 1.20) and CD69 (MFI = 2.45) expression in C+P-group compared to Burn/CLP-group (MFI = 1.46; p = 0.0215 and MFI = 3.58; p = 0.0347). In CD4+ T cells the enhancement of extracellular markers CD38 (p = 0.0130) and MHC II (p = 0.0330) proved an increased activity. This was underlined by elevated intracellular signal molecules ZAP-70 (p = 0.0002) and PKC-θ (p = 0.0001) as well as their phosphorylated forms with distinct differences between CD4+ Tregs and nonTregs. (ZAP-70: p = 0.0153; PKC-θ: p = 0.0085). In platelets we found a decreased expression of the activation marker CD62 (p = 0.0229).</p><p><strong>Conclusion: </strong>Curcumin + piperine improves the long-term outcome in a murine two-hit trauma model. It can balance the post-traumatic immune response by its effect on T cells and platelets. CD4+ Tregs seem to be primed for further activation, whereas downregulation of CD8+ T cell and platelet response may reduce proinflammatory signals. This defines curcumin (+ piperine) a promising substance for further investigation.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081480","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":"Impact of Desmopressin on Clinical Outcomes in Patients with Spontaneous Antiplatelet-Associated Intracerebral Hemorrhage Undergoing Neurosurgical Intervention: An Observational Multi-Center Study.","authors":"Hsu Pang-Ting, Shuo-Chi Chien, Ching-Chang Chen, Zhuo-Hao Liu, Chi-Cheng Chuang, Yu-Chen Tsai, Chung-Hsien Chaou, Chieh-Ching Yen","doi":"10.1097/SHK.0000000000002694","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002694","url":null,"abstract":"<p><strong>Objective: </strong>Managing surgical cases of acute spontaneous intracerebral hemorrhage (ICH) in patients with antiplatelet therapy presents significant challenges due to the heightened risk of bleeding. Desmopressin acetate (DDAVP) is commonly employed as a management strategy. This multi-center study aims to compare the functional and safety outcomes in patients with or without preoperative DDAVP administration after spontaneous antiplatelet-associated ICH.</p><p><strong>Methods: </strong>From January 2016 to November 2023, we enrolled patients with spontaneous ICH who were under antiplatelet therapy and needed neurosurgical interventions in the emergency departments. Patients were excluded for traumatic brain injury, ICH from subarachnoid hemorrhage, arteriovenous malformation, intracranial tumors, coagulopathies, and anticoagulant use. The primary outcome was the modified Rankin Scale (mRS) 4 - 6 at discharge. Secondary endpoints included safety outcomes, in-hospital and follow-up outcomes.</p><p><strong>Results: </strong>A total of 75 patients were included, comprising 26 patients treated with DDAVP and 49 patients in the control group. After inverse probability of treatment weighting adjustment, there were no significant differences in baseline characteristics. There were no significant differences in mRS of 4 - 6 at discharge between groups (84.3% vs 88.2%; p = 0.692). Multivariable generalized estimating equations logistic regression demonstrated DDAVP was not significantly associated with improved functional outcome, safety outcomes, in-hospital or follow-up outcomes.</p><p><strong>Conclusion: </strong>This study demonstrated no significant difference in mRS at discharge or SAEs between patients with and without DDAVP administration. However, this null finding should be interpreted cautiously due to the study being underpowered. Further randomized controlled trials are warranted to validate our findings.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081461","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":"Solvent-Detergent Treated Pooled Human Plasma Provides Superior Hemodynamic Stability and Cerebral Tissue Oxygenation Compared to Crystalloid in a Cynomolgus Macaque Model of Traumatic Hemorrhagic Shock.","authors":"Leslie E Neidert, Alejandra L Lorenzen, Peter J Hemond, Erica M Molina, Charles F Schwarten, Emily M Corbin, Dominic Lonowski, Anthony E Pusateri, Michael M Tiller, Clifford G Morgan","doi":"10.1097/SHK.0000000000002686","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002686","url":null,"abstract":"<p><strong>Background: </strong>Clinical trauma studies have demonstrated a long-term survival benefit of early plasma resuscitation compared to crystalloid, with conflicting evidence for improvements in coagulation parameters. To further elucidate resuscitative effects of plasma, we evaluated solvent/detergent-treated pooled human plasma (SDP) in a nonhuman primate model of polytrauma and hemorrhagic shock (PTHS).</p><p><strong>Methods: </strong>Ten anesthetized male cynomolgus macaques underwent PTHS before randomization to receive 20mL/kg of SDP or Lactated Ringers (LRS) at the end of shock (T0). All animals underwent standardized simulated hospital resuscitation at T60, with injury repair and 50% shed blood return followed by 300% shed blood volume in LRS. Data analyzed via t-tests and two-way repeated measures ANOVA. Significance=P<0.05.</p><p><strong>Results: </strong>No significant group differences were observed in shock time, blood loss, or resuscitative fluid volumes. At T0, mean arterial pressure (MAP), systolic blood pressure (SBP), and cerebral oxygen saturation (CrSO₂) significantly decreased in both groups. While both groups normalized MAP and SBP by T5, only SDP maintained these levels until the simulated hospital period. CrSO₂ remained significantly lower in the LRS group until simulated hospital resuscitation. SDP significantly improved colloid osmotic pressure (COP) compared to LRS. Coagulation analysis showed increased fibrinogen concentration and coagulation factor activities in the SDP group compared to LRS.</p><p><strong>Conclusion: </strong>SDP provides significantly more stable hemodynamic function following PTHS compared to LRS, maintaining MAP, SBP, and CrSO₂ despite both fluids lacking oxygen-carriers, likely due to increased COP, while supporting coagulation. These findings support SDP as a viable resuscitation product for PTHS in austere settings.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150714","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":"RBM15-mediated VEGFA m6A methylation drives M1 pro-inflammatory macrophage polarization and suppresses M2 anti-inflammatory polarization in acute lung injury.","authors":"Jin Yang, Guangsheng Ni, Xiao Xie, Zhaojun Xu","doi":"10.1097/SHK.0000000000002697","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002697","url":null,"abstract":"<p><strong>Background: </strong>Acute lung injury (ALI), recognized as a prevalent and severe respiratory disorder, represents a critical medical condition. During ALI, Vascular Endothelial Growth Factor A (VEGFA)-mediated M1/M2 macrophage polarization is crucial, yet its specific regulatory mechanisms remain unclear.</p><p><strong>Methods: </strong>THP-1 cells were treated with lipopolysaccharide (LPS)/interferon-γ (IFN-γ). VEGFA expression in the serum of ALI patients was identified using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). Flow cytometry was employed to identify the expression of M1 and M2 polarization markers. Inflammatory cytokines were detected by ELISA. Bioinformatics was employed to predict the m6A sites on VEGFA mRNA, and Western blot was conducted to examine the protein levels. Methylated RNA immunoprecipitation (MeRIP), and RIP assays were used to verify the modification and binding between RBM15 and VEGFA. Actinomycin D assay was performed to evaluate the mRNA stability. An ALI mouse model was established to assess the in vivo role of the RBM15/VEGFA axis. HE staining was used to assess the lung tissue injury of mice. Meanwhile, myeloperoxidase (MPO) activity was measured using colorimetry.</p><p><strong>Results: </strong>VEGFA exhibited elevated expression in the serum of ALI patients and LPS/IFN-γ-induced THP-1/M0 cells. Additionally, VEGFA inhibitor and silencing VEGFA restrained M1 polarization and contributed to M2 polarization of LPS/IFN-γ-induced THP-1/M0 cells accompanied by the reduction in the levels of pro-inflammatory cytokines (TNF-α, IL-12, IL-6, and IL-1β) and the relative increase in the anti-inflammatory cytokine (IL-10). Moreover, VEGFA expression was promoted by RBM15 through m6A modification. The RBM15/VEGFA axis promoted the M1 polarization while inhibiting the M2 polarization of LPS/IFN-γ-induced THP-1/M0 cells. ALI was alleviated by inhibiting the RBM15/VEGFA axis in vivo.</p><p><strong>Conclusion: </strong>RBM15 enhanced VEGFA expression through m6A modification, thereby promoting M1 polarization, inhibiting M2 polarization of macrophages, and facilitating the progression of ALI.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081535","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}