SHOCK最新文献

{"title":"COMBINATION OF ANTIOXIDANTS AND TARGETED TEMPERATURE MANAGEMENT AMELIORATES POSTCARDIAC ARREST SYNDROME IN A RAT MODEL OF ASPHYXIAL CARDIAC ARREST.","authors":"Jingru Li, Xue Liu, Jianjie Wang, Bihua Chen, Yongqin Li","doi":"10.1097/SHK.0000000000002616","DOIUrl":"10.1097/SHK.0000000000002616","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Postcardiac arrest syndrome (PCAS) is a complex pathophysiological processes occurring after return of spontaneous circulation (ROSC) following cardiac arrest (CA), which may lead to multiple organ failure and death. The clinical efficacy of conventional therapies such as oxygen therapy and targeted temperature management (TTM) are remaining limited. Given the central role of oxidative stress in the progression of PCAS, we investigated the effect of combining antioxidants with TTM in an asphyxial CA rat model. Methods and Results: After 7 min of untreated asphyxial CA in Sprague-Dawley rats, animals were randomized into four groups: 1) placebo control (PBO); 2) trimetazidine (TMZ); 3) edaravone (EDA); 4) TMZ + EDA. Glucose (10 mL/kg), TMZ (10 mg/kg), saline (10 mL/kg), and EDA (3 mg/kg) were administered at 5 and/or 60 min after resuscitation. Animals were ventilated with 100% O 2 for 1 h after ROSC. Half of the animals were maintained at normothermia (37.5°C) and half at hypothermia (34.0°C). Under normothermia, the administration of EDA significantly improved 96-h survival rates, reduced the proportion of FJB-positive areas in the hippocampus and decreased malondialdehyde and 8-OHDG levels compared to normothermia PBO. Under hypothermia, the 96-h survival rates were markedly higher in TMZ, EDA, and TMZ + EDA groups than in hypothermia PBO. Furthermore, collagen volume fraction and the proportion of FJB-positive areas were markedly reduced, while malondialdehyde, 8-OHDG, and H 2 O 2 were significantly decreased in TMZ + EDA group. Conclusions : Combining antioxidants with TTM alleviates PCAS and improves outcomes by reducing reactive oxygen species levels and mitigating myocardial and cerebral pathological injury.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"425-434"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037558","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 VALUE OF HEPARIN-BINDING PROTEIN IN PREDICTING EARLY PNEUMONIA IN NEUROSURGICAL INTENSIVE CARE UNIT PATIENTS.","authors":"Qiang Li, Linrui Qi, Xin Geng, Hongming Ji, Liru Feng, Dan Wu, Hao Wu, Zhongmin Li, Xinmin Ding, Lei Ji","doi":"10.1097/SHK.0000000000002656","DOIUrl":"10.1097/SHK.0000000000002656","url":null,"abstract":"<p><strong>Abstract: </strong>Background: The high incidence of pneumonia in neurosurgical intensive care unit (NICU) patients significantly impacts their prognosis. Early identification of high-risk individuals for pneumonia is crucial for timely intervention and personalized treatment. Heparin-binding protein (HBP), an early inflammatory marker, shows promise as a predictor for early-onset pneumonia. Methods: This study enrolled a prospective cohort of 389 NICU patients. Logistic regression analysis was used to identify risk factors for early pneumonia while accounting for the potential confounding effects of other variables on HBP. Restricted cubic splines (RCS) were employed to explore the potential nonlinear relationship between HBP and the risk of early pneumonia. Subgroup analyses were conducted to evaluate the sensitivity of HBP as a risk factor. A nomogram integrating HBP and four other independent risk factors was developed to predict early pneumonia. The performance of the model was assessed using receiver operating characteristic curves, calibration plots, and decision curve analysis. Results: A total of 300 NICU patients were included, among whom 201 developed early pneumonia. Multivariate logistic regression confirmed HBP as an independent risk factor for early pneumonia, with consistent results across all subgroups. The nomogram demonstrated excellent predictive performance, achieving high discrimination (AUC = 0.89) and calibration (Hosmer-Lemeshow test, P = 0.520). Additionally, the model showed significant clinical utility. Conclusions: Elevated HBP levels are independently associated with the risk of early pneumonia in NICU patients. The nomogram integrating HBP provides accurate predictions for early pneumonia.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"405-413"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643357","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 RESPONSE BY POLYMYXIN B HEMOPERFUSION AND ITS CLINICAL OUTCOMES IN PATIENTS WITH REFRACTORY SEPTIC SHOCK: A POST-HOC SUBANALYSIS OF PROSPECTIVE COHORT STUDY.","authors":"Kyohei Miyamoto, Yu Kawazoe, Noriko Miyagawa, Hitoshi Yamamura, Yoshinori Ohta, Takuya Kimura, Yukitoshi Toyoda, Michihito Kyo, Tetsuya Sato, Masashi Kinjo, Masaki Takahashi, Junichi Maruyama, Hiroshi Matsuura, Kazunori Fukushima, Satoru Murata, Tomoya Okazaki, Tsuyoshi Suzuki, Toshihiro Sakurai, Gaku Takahashi, Tasuku Hanajima, Takeshi Morimoto","doi":"10.1097/SHK.0000000000002654","DOIUrl":"10.1097/SHK.0000000000002654","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Polymyxin B hemoperfusion (PMX-HP) reportedly improves hemodynamic status in some but not all patients with septic shock. We examined the association between hemodynamic response and clinical outcomes and explored factors that may identify patients with hemodynamic response. Methods: BEAT-SHOCK registry is a prospective cohort study of 309 consecutive adult patients with septic shock requiring high-dose norepinephrine. This predefined subanalysis included 82 patients treated with PMX-HP. We defined hemodynamic response as a ≥ 20% improvement within 6 h of starting PMX-HP in the modified vasopressor dependency index, representing vasopressor dosage divided by mean arterial pressure. Results: The median modified vasopressor dependency index at the start of PMX-HP was 0.56 mmHg -1 , and 0.34 mmHg -1 6 h after starting PMX-HP (median relative change -32%). Hemodynamic response was obtained in 53 patients (65%; responder group). The 28-day mortality rate was 8% (4/53) in the responder group and 31% (9/29) in the nonresponder group ( P = 0.0042). Three potential factors were: lower Sequential Organ Failure Assessment score (≤10, adjusted odds ratio [aOR] 3.36), abdominal or urinary tract infection (aOR 2.49), and higher modified vasopressor dependency index at the start of PMX-HP (≥0.5 mmHg -1 , aOR 2.14). Patients with two or three factors were likely to respond to PMX-HP. Conclusions: Among patients with refractory septic shock, 65% had hemodynamic response after PMX-HP, and it was associated with better clinical outcomes, as shown by the higher survival rate. The number of the following factors was associated with the likelihood of hemodynamic response: less organ dysfunction, more vasopressors, and abdominal/urinary tract infection. Trial registration: UMIN Clinical Trial Registry on 1 November 2019 (registration no. UMIN000038302).</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"397-404"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476643","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":"STAT3/HIF1Α AXIS PROMOTES NEURONAL FERROPTOSIS IN SEPSIS-ASSOCIATED ENCEPHALOPATHY: BASED ON TRANSCRIPTOMIC ANALYSIS.","authors":"Xu-Ri Sun, Run Zhang, Jin-Kai Wu, Hong-Guang Cai, Wei Wang","doi":"10.1097/SHK.0000000000002646","DOIUrl":"10.1097/SHK.0000000000002646","url":null,"abstract":"<p><strong>Abstract: </strong>Background: This study aimed to provide novel insights for revealing the potential molecular mechanisms of ferroptosis in sepsis-associated encephalopathy (SAE). Methods: Three independent SAE datasets were obtained from the GEO database. The differentially expressed genes (DEGs) were then intersected with ferroptosis-related markers. The intersected genes were further analyzed for the identification of ferroptosis-related DEGs (FRDEGs) and main pathways via protein-protein interaction network construction and enrichment analysis. The related pathway targets were further verified at the mRNA and protein expression level. Results: We demonstrated 121 highly expressed genes and 19 lowly expressed genes that play critical roles in SAE. Intersecting these DEGs with ferroptosis-related markers, we identified 11 FRDEGs. We constructed a protein-protein interaction network of the 11 FRDEGs and found Stat3 showed the highest degree score. In addition, KEGG pathway analysis showed that the 11 FRDEGs were predominantly involved in HIF-1 signaling pathway. The results from animal experiments indicated that sepsis upregulated the mRNA and protein expression levels of Stat3/HIF-1α axis in hippocampal tissue of SAE mice. In addition, we found that sepsis caused hippocampal ferroptosis, as evidenced by an increase in ferroptosis-related proteins and malondialdehyde, and a decrease in glutathione level. In contrast, treatment with Stat3 inhibitor attenuated hippocampal ferroptosis and decreased the mRNA and protein level of HIF-1α in hippocampal tissue of SAE mice. Conclusion: In conclusion, our study demonstrated that sepsis might induce the activation of hippocampal ferroptosis by triggering the Stat3/HIF-1α axis, thereby providing a novel therapeutic target for SAE.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"442-449"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643356","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":"Assessment of Sublingual Microcirculation to Evaluate the Efficacy of Resuscitation Therapy in Septic Shock Patients: A cohort study.","authors":"Xiaolei Zhang, Haisong Zhang, Rui Jin, Li Li, Li Huang, Zhanwen Wang, Qianyi Peng, Meilin Ai, Lina Zhang","doi":"10.1097/SHK.0000000000002708","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002708","url":null,"abstract":"<p><strong>Objectives: </strong>Determining the endpoint of resuscitation in septic shock is essential to enhance effectiveness, prevent over-resuscitation, and improve outcomes. We designed this study to investigate whether sublingual microcirculation monitoring can serve as an effective marker for assessing the efficacy of resuscitation therapy in septic shock.</p><p><strong>Methods: </strong>A total of 72 septic shock patients were included in our final analysis, excluding those with heart function impairments, including sepsis-induced cardiomyopathy. Sublingual microcirculation parameters were measured at two time points: prior to resuscitation and 6 hours post-resuscitation. Additionally, the values of macrocirculatory parameters, blood gas analysis variables, and organ prognosis indicators were collected at multiple time points before and after resuscitation. Spearman correlation analysis was performed to assess the correlations among these variables. Furthermore, the ROC curve analysis method was employed to evaluate the predictive performance of sublingual microcirculation parameters and other relevant factors for patient prognosis. Finally we determined the optimal threshold of PPV6h by anchoring it to three key aspects: tissue oxygenation (Lac24h), organ dysfunction progression (△APACHE II3d and △SOFA3d), and long-term outcomes (Adverse Prognosis and 28-day mortality).</p><p><strong>Results: </strong>Sublingual microcirculation variables post-resuscitation showed no significant correlation with conventional circulation variables. PPV6h had the highest predictive efficacy for 28-day prognosis, better than PcvO26h, the best predictor among conventional variables. The optimal PPV6h threshold (68.6%) was determined using three key criteria mentioned above. Patients meeting this threshold after resuscitation showed improved microcirculation (lower lactate levels and faster clearance), reduced organ dysfunction (lower APACHE II and SOFA scores, less need for CRRT), and better long-term outcomes (fewer vasoactive drugs, 28-day lower mortality).</p><p><strong>Conclusions: </strong>Our study highlights the potential utility of sublingual microcirculation as an adjunctive tool for reflecting the effectiveness of resuscitation therapy and proposes that the PPV6h > 68.6% may serve as a target for early goal-directed therapy in future studies.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200842","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":"A PILOT STUDY ON LONG-TERM OBSERVATION OF SEPTIC MICE: HISTORY OF SEVERE INFECTIONS MAY ACCELERATE HOST SENESCENCE EVEN 18 MONTHS LATER.","authors":"Masafumi Saito, Yuko Ono, Yoshihisa Fujinami, Yusuke Miyazaki, Kimihiro Yamashita, Shigeaki Inoue, Joji Kotani, Manabu Kinoshita","doi":"10.1097/SHK.0000000000002655","DOIUrl":"10.1097/SHK.0000000000002655","url":null,"abstract":"","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"450-452"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476563","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":"AZITHROMYCIN REGULATES ANXA1-SUPPRESSED NOTCH1/NF-ΚB PATHWAY TO INHIBIT M1 MACROPHAGE POLARIZATION AND ATTENUATES LPS-INDUCED AKI.","authors":"Qiuyi Li, Yuxuan Lei, Rui Zhou, Hongxuan Chen","doi":"10.1097/SHK.0000000000002641","DOIUrl":"10.1097/SHK.0000000000002641","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Acute kidney injury (AKI) is a common and severe form of renal dysfunction, characterized by inflammation and damage to tubular epithelial cells. Azithromycin (AZM) possesses anti-inflammatory and immunomodulatory properties. In this study, we aim to elucidate the underlying functional roles of AZM in lipopolysaccharide (LPS)-induced AKI. Methods: C57BL/6 mice (7 weeks old) were used to construct the AKI models in vivo . The serum creatinine (Scr) level, blood urea nitrogen (BUN) levels, tubular damage score, and NGAL-positive expression were examined using Scr and BUN assay kits, hematoxylin and eosin staining, and immunohistochemistry, respectively. The reverse transcription-quantitative polymerase chain reaction (qRT-PCR) and western blot were performed to detect the levels of target genes. The cell viability was examined using cell counting kit-8 (CCK8). The interleukin (IL)-6, IL-1β, tumor necrosis factor-alpha (TNF-α), and IL-10 levels were analyzed using corresponding enzyme-linked immunosorbent (ELISA) detection kits. The macrophage polarization was detected using western blot and flow cytometry. Results: AZM reduced Scr level, BUN levels, tubular damage score, and NGAL-positive expression rate in LPS-induced AKI model in vivo . AZM repressed IL-6, IL-1β, TNF-α, inducible nitric oxide synthase (iNOS), and CD86 levels and promoted IL-10 and Arginase-1 levels in LPS-induced AKI group. Additionally, AZM suppressed LPS-induced M1 macrophage polarization in vitro . AZM expedited ANXA1 expression and inhibited notch receptor 1 and nuclear factor kappa B subunit 1 expression in vivo and in vitro . Furthermore, AZM alleviated inflammation and M1 macrophage polarization through ANXA1 upregulation. Conclusion: AZM remits LPS-induced AKI by regulating M1 macrophage polarization via regulating ANXA1 and notch receptor 1/nuclear factor kappa B subunit 1 pathway. These findings may accelerate the translation of clinical drugs for the treatment of LPS-associated AKI.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"435-441"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643350","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":"CIRCULATING INFLAMMATORY PROTEINS IN DRUG-INDUCED ANAPHYLACTIC SHOCK: EVIDENCE FROM MULTIVARIABLE MENDELIAN RANDOMIZATION AND MULTIOMICS INTEGRATION.","authors":"Jinwei Dai, Nianzhe Sun, Wenye Xu, Zhihong Zuo, Xiaoyang Pang, Zhaoxin Qian","doi":"10.1097/SHK.0000000000002644","DOIUrl":"10.1097/SHK.0000000000002644","url":null,"abstract":"<p><strong>Abstract: </strong>Background : Drug-induced anaphylactic shock (DIAS) remained a critical clinical challenge due to increased drug use and novel hypersensitivity mechanisms. The role of circulating inflammatory proteins in DIAS remained unclear. Methods: We applied multivariable Mendelian randomization (MR) to explore the associations between specific inflammatory proteins and DIAS, drawing on recent findings from genome-wide association studies. Circulating inflammatory protein data were obtained from a cohort of European ancestry comprising 14,824 samples, while data on DIAS were sourced from the FinnGen consortium, including 20,806 cases and 411,845 controls. To strengthen our findings, we conducted complementary analyses such as colocalization (COLOC), enrichment studies, drug screening, and molecular docking. Results: MR analysis identified significant associations between inflammatory proteins and DIAS. CD40L exhibited a protective effect (OR = 0.69, 95% CI: 0.4951-0.9578, P = 0.027) and high colocalization probability (58%). CXCL10 (OR = 1.51, 95% CI: 1.0075-2.2549, P = 0.046) and CCL3 (OR = 2.08, 95% CI: 1.0079-4.3072, P = 0.048) significantly increased risk. Drug screening and enrichment analyses further elucidated underlying molecular mechanisms. Conclusions : This study identified novel associations between inflammatory proteins and the risk of anaphylaxis, providing insights for targeted prediction and therapeutic strategies.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"380-385"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691413","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":"LACTATE TRAJECTORIES IN EARLY SURVIVORS OF SEPSIS: A NEW LENS ON MORTALITY RISK.","authors":"Zhihui Liang, Min Zhao, Kaiting Liu, Weican Liang, Shaofang Luo, Jianbin Guan, Zongmian Zhang","doi":"10.1097/SHK.0000000000002653","DOIUrl":"10.1097/SHK.0000000000002653","url":null,"abstract":"<p><strong>Abstract: </strong>Background: The evolution of lactate levels reflects the complex pathophysiological processes in sepsis. Whether distinct subclusters of sepsis exhibit different lactate trajectories remains unclear. This study aimed to identify novel clusters of sepsis based on lactate trajectories and investigate the association between lactate trajectory and mortality risk and to develop a predictive model for unfavorable lactate trajectories. Methods: Early survivors diagnosed with sepsis were included. A group-based trajectory model was constructed to identify distinct lactate trajectories. Doubly robust estimation models were utilized to assess the association between each cluster and mortality risk. A cross-lagged panel model was applied to examine the temporal causal relationship between lactate levels and Sequential Organ Failure Assessment (SOFA) score. LASSO-logistic regression was used to develop a predictive model for unfavorable lactate trajectories. Results: A total of 4,870 patients from two critical care medicine databases were included. The following 4 lactate trajectory clusters were identified: (1) hyperlactatemia, gradual resolution (cluster 1; 14.0%), (2) consistent near-normal lactate level (cluster 2; 81.5%), (3) extreme hyperlactatemia at admission but with prompt clearance (cluster 3; 2.0%), and (4) consistent hyperlactatemia (cluster 4; 2.5%). Comparisons were conducted using cluster 1 as the reference. Cluster 2 showed reduced 28-day mortality risk (hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.65 to 0.89), while no difference was observed in adjusted mortality hazard risk. Clusters 3 and 4 had higher mortality risks (HR 1.94; 95% CI 1.40 to 2.67 and HR 3.87; 95% CI 2.98 to 5.03 respectively) compared to cluster 1. The cross-lagged panel model analysis showed a bidirectional causal relationship between lactate levels and organ dysfunction (Lactate→SOFA,β = 0.310, P < 0.001 vs. SOFA→Lactate,β = 0.037, P < 0.001). A nomogram with five variables was developed to identify unfavorable lactate trajectories. Conclusion: Lactate trajectories are significantly associated with mortality risk in early-survival patients with sepsis, which provides a valuable framework for risk stratification in sepsis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"386-396"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732957","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":"PHYSIOLOGICAL FRACTURE HEALING IS UNAFFECTED BY NEUTROPHIL-DERIVED IL-6 OR IL-6R SIGNALING IN MICE.","authors":"Verena Fischer, Oliver Küppers, Lena Steppe, Benjamin Thilo Krüger, Juan Hidalgo, Melanie Haffner-Luntzer, Anita Ignatius","doi":"10.1097/SHK.0000000000002615","DOIUrl":"10.1097/SHK.0000000000002615","url":null,"abstract":"<p><strong>Abstract: </strong>Background : Neutrophils are the predominant immune cell type in the early fracture hematoma, playing key roles in orchestrating the immune response and bone repair by clearing pathogens and debris, producing extracellular traps and proteases, and releasing various signaling molecules. However, neutrophil roles in fracture healing remain incompletely understood. They are a key source of interleukin-6 (IL-6) and the soluble IL-6 receptor (sIL-6R), driving both IL-6 classic signaling via membrane-bound IL-6R and trans-signaling via sIL-6R. Classic signaling drives neutrophil infiltration into the fracture hematoma and is crucial for bone repair, whereas trans-signaling impairs healing after severe trauma. Here, we examined neutrophil-specific IL-6 signaling in fracture healing. Methods : We used male mice with neutrophil-specific deletion of IL-6 or IL-6R . Physiological bone phenotype and effects on fracture healing (external fixator stabilized femur osteotomy) were assessed in 12-week-old mice by flow cytometry, cytokine multiplex analysis, biomechanical testing, micro-computed tomography, and histomorphometry. Results : While neutrophil-specific deletion of IL-6 or IL-6R did not affect bone under physiological conditions, IL-6R deletion led to a reduction in neutrophils and macrophages and an increase in T lymphocytes. The immune response to fracture was unaffected by either deletion, because cytokine levels in the fracture hematoma and serum remained unchanged compared to controls after 6 h. Additionally, the biomechanical properties of fractured femurs together with structural and cellular bone parameters on day 21 did not differ compared to controls. Conclusions : Neutrophil-induced IL-6 signaling appears nonessential for physiological bone turnover and fracture healing. Its role in impaired healing under conditions of excessive inflammation remains to be determined.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"414-424"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080076","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}