SHOCK最新文献

{"title":"miR-eQTLs reveals causal association and regulatory mechanism of miRNAs and sepsis.","authors":"Ruiming Deng, Yuhui Xu","doi":"10.1097/SHK.0000000000002651","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002651","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, and its pathogenesis remains unclear. miRNAs play crucial roles in regulating gene expression and have been implicated in various diseases, including sepsis.</p><p><strong>Methods: </strong>This study investigated the causal associations of miR-expression quantitative trait loci (miR-eQTL) with sepsis through mendelian randomization (MR) analysis. We analyzed 2083 miR-eQTLs using the inverse variance weighting (IVW) method and validated the results with sensitivity analyses. We obtained mRNA targets of these miRNAs and performed pathway enrichment analysis and PPI network construction. Additionally, using 11 topological algorithms, we analyzed the PPI network to determine the core genes of target genes.</p><p><strong>Results: </strong>The findings revealed that 74 miRNAs were causally associated with sepsis, with 33 acting as protective factors and 41 as risk factors. A stringent filtering approach identified 9 miRNAs, including miR-6775-3p, miR-1296-3p, miR-4317, miR-3144-3p, miR-4798-3p, miR-581, miR-3185, miR-221-3p, and miR-340-5p. Sensitivity analyses confirmed the robustness of these associations, with no significant heterogeneity, pleiotropy, or directionality issues. Through pathway enrichment analysis and PPI network construction, we identified core genes. The pathway enrichment analysis highlighted significant enrichments in various biological processes and pathways, including the FoxO signaling pathway, Wnt signaling pathway, and Ras signaling pathway. Using 11 topological algorithms, we screened out 25 PPI core genes. The miRNA-mRNA interaction network further elucidated the regulatory roles of these miRNAs.</p><p><strong>Conclusion: </strong>This study offers new insights into miRNA-mediated mechanisms in sepsis and identifies potential therapeutic targets for this complex syndrome, though additional validation is necessary.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699395","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":"Intravenous delivery of long-acting DNase I (PRX-119) in a murine model of polymicrobial abdominal sepsis.","authors":"Neha Sharma, Dhruva J Dwivedi, Liat Fux, Yael Hayon, Erblin Cani, Ji Zhou, Patricia C Liaw","doi":"10.1097/SHK.0000000000002666","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002666","url":null,"abstract":"<p><strong>Objective: </strong>Sepsis is a life-threatening complication of infection in which a dysregulated host response precipitates multi-organ dysfunction. Neutrophil extracellular traps (NETs) contribute to infection-induced immunothrombosis by releasing cell-free DNA (cfDNA), which provides a prothrombotic scaffold for blood clots. Although DNase I has therapeutic promise due to its ability to degrade cfDNA, its short plasma half-life (2 to 4 hours) may necessitate multiple daily injections, potentially posing challenges for clinical use. This study investigates the efficacy of intravenous administration of PRX-119, a PEGylated recombinant human DNase I with an extended half-life of ~12 hours.</p><p><strong>Methods: </strong>Sepsis was induced in C57Bl/6 mice (10 to 12 weeks old) using the cecal ligation and puncture (CLP) model. The efficacy of intravenous PRX-119 (1 mg/kg) was tested in 72-hour and 7-day survival studies, including clinically relevant supportive therapies (antibiotics, fluid resuscitation). We measured plasma levels of cfDNA, IL-6, IL-10, and thrombin-antithrombin (TAT) complexes. We assessed physiological parameters, bacterial burden, lung myeloperoxidase (MPO), and organ injury/function.</p><p><strong>Results: </strong>Using both sexes, a single dose of PRX-119 (at T = 8 hours) or two doses (at T = 4 and T = 24 hours) improved survival at 72 hours. Using male mice, we observed that three doses (at T = 4 h, 20 h, and 36 h post-CLP) provided a sustained protective effect at 7 days post-CLP. PRX-119 treatment reduced cfDNA, IL-6, TAT, lung MPO, and bacterial load. PRX-119 treatment also reduced organ injury.</p><p><strong>Conclusions: </strong>Intravenous delivery of PRX-119 improved survival and reduced immunothrombosis and organ injury, without the need for frequent injections.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic evaluation of molecular endotypes in sepsis: a multicenter cohort study in Brazil.","authors":"Fernanda do Carmo De Stefani, Ana Carolina de Miranda, Bruna Cassia Dal Vesco, Dalila Luciola Zanette, Anelis Maria Marin, Luis Gustavo Morello, Igor Alexandre Côrtes de Menezes","doi":"10.1097/SHK.0000000000002661","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002661","url":null,"abstract":"<p><strong>Background: </strong>Sepsis heterogeneity affects the identification of high-risk patients. Outcomes in low- and middle-income countries are worse than those in developed nations. This study aimed to assess the prognostic potential of the previously described molecular endotypes, Mars1, Mars2, Mars3, and Mars4, in a Brazilian cohort with sepsis.</p><p><strong>Material and methods: </strong>This prospective, multicenter, observational study identified molecular expression-based endotypes in adults from four intensive care units in Brazil. Patients on their first 24-hour diagnosis of sepsis based on the Sepsis 3 criteria were included. Health care workers were included in the control group. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify the transcripted levels of eight genes and determine the four endotypes. The primary endpoint was 28-day mortality with a secondary analysis of diagnostic accuracy. Statistical significance was set at P < 0.05.</p><p><strong>Results: </strong>One-hundred-sixty-eight participants and twenty-five controls were enrolled in this study. The overall mortality rate was 44%. The Mars1 group showed a higher 28-day mortality than the non-Mars1group. The log-rank test showed a worst survival probability in Mars1 subgroup (P = 0.013), and the hazard ratio was 1.78 (P = 0.017). Compared to control, area-under-the-curve (AUC) of ROC curves for diagnosing sepsis were: 0.69 for Mars1 (SD 0.62-0.77 / P = 0.0016), 0.89 for Mars2 (SD 0.85-0.94 / P < 0.0001), 0.82 for Mars3 (SD 0.75-0.88 / P < 0.0001) and 0.71 for Mars4 (SD 0.64-0.79 / P < 0.0006).</p><p><strong>Conclusion: </strong>The Mars1 endotype detected by qRT-PCR was associated with worse sepsis survival in low-to middle-income countries. We also identified the Mars 2 endotype as a potential diagnostic marker for sepsis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699397","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":"Advanced Age in Mice Exacerbates Sepsis-Induced Inflammation, Vascular Permeability, and Multi-Organ Dysfunction.","authors":"Han Noo Ri Lee, Jason Lin, Camryn J Smith, Lorraine B Ware, Fiona E Harrison, Julie A Bastarache, Brandon Baer","doi":"10.1097/SHK.0000000000002657","DOIUrl":"10.1097/SHK.0000000000002657","url":null,"abstract":"<p><strong>Abstract: </strong>Sepsis is a life-threatening syndrome marked by a dysregulated immune response to an infection and significant endothelial vascular permeability, often leading to multi-organ failure. Elderly patients are particularly vulnerable to sepsis, with higher morbidity and mortality rates. We hypothesized that advanced age exacerbates sepsis-induced inflammation and endothelial vascular permeability, resulting in a delayed recovery, persistent inflammation, and sustained organ injury. Using a polymicrobial sepsis model in young (3-month-old) and aged (18-month-old) C57BL/6 mice, sepsis was induced via intraperitoneal cecal slurry (CS) injection. Outcomes were assessed during the acute (24-hour; 1.6 mg/g CS) and recovery (8-day; 1.0 mg/g CS) phases. During the acute phase, aged mice exhibited worse physiologic dysfunction, higher systemic (plasma TNF-a: young septic 202.1 pg/mL [17.44, 398.9] vs. aged septic 482.6 pg/mL [279.8, 711.7]; p = 0.0352 Mann-Whitney) and organ-specific inflammation, increased endothelial injury and vascular permeability, as well as greater kidney and liver dysfunction compared to young mice. During recovery, aged mice had sustained physiologic dysfunction, prolonged systemic and organ-specific inflammation, and sustained organ injury (kidney tissue NGAL: young septic 291.5 RE [203.7, 373.2] vs. aged septic 821 RE [456, 1258] protein normalized to beta actin; p = 0.0008 Mann-Whitney) compared to young mice. These results support the hypothesis that advanced age worsens sepsis severity and outcomes and delays recovery, emphasizing the need for aged models and multi-organ evaluations to develop effective therapies for this vulnerable population.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643349","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":"Trauma and Hemorrhage Lead to an Elevation in Fecal Short-Chain Fatty Acids.","authors":"Daniel N Darlington, Reese B Berger, Jeffrey D Keesee, Susannah E Nicholson, Xiaowu Wu","doi":"10.1097/SHK.0000000000002645","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002645","url":null,"abstract":"<p><strong>Introduction: </strong>Severe trauma and hemorrhage in rats lead to changes in the beta diversity of the commensal bacteria found in the gut. Because Short-Chain Fatty Acids (SCFA) are produced by these bacteria, SCFA concentration may also change following trauma and hemorrhage and reflect these alterations in the microbiome.</p><p><strong>Objective: </strong>To determine whether changes in SCFA occur after trauma and hemorrhage in the feces and plasma of rodents.</p><p><strong>Materials and methods: </strong>Polytrauma was induced in isoflurane-anesthetized Sprague-Dawley rats by damage to the small intestine, liver, right leg skeletal muscle, and femur, followed by 20% hemorrhage. Whole blood resuscitation was performed at 1 hour (20%). Rats were euthanized at 2 hours and feces and plasma were analyzed for short-chain fatty acids (SCFA) by liquid chromatography tandem mass spectroscopy.</p><p><strong>Results: </strong>Of twenty-one SCFA analyzed in the feces and plasma, 11 were measurable. In feces, five demonstrated a significant elevation after 2 hours of severe trauma and hemorrhage (n-8) including propionic (37775 ± 8919 vs. 146591 ± 46734 nM/mg protein: mean ± SEM), pentanoic (10975 ± 2981 vs. 41828 ± 10645), 2-methyl propionic (2621 ± 523 vs. 13798 vs. 2083), 4-methyl pentanoic (1134 ± 302 vs. 4320 ± 1029) and 3-phenyl propionic acid (42194 ± 4863 vs. 153024 ± 38473). The addition of whole blood resuscitation did not change these responses, but led to an additional significant elevation in butyric (68551 ± 10786 vs. 369951 ± 79515) and hexanoic acid (24548 ± 6791 vs. 102002 ± 32069). There was no change in SCFA after trauma, hemorrhage or resuscitation in the plasma (n = 6).</p><p><strong>Conclusion: </strong>Two hours of severe trauma and hemorrhage lead an elevation in many SCFAs in rat feces. No change in SCFA was found in plasma. Because SCFA are primarily derived from commensal bacteria in the gut, these data suggest that the measurement of SCFA could be used as an index of changes in the gut microbiome in pathological condition including trauma and hemorrhage.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498027","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":"Resuscitation from Hemorrhagic Shock With a Novel Protein Cocktail Restores Microvascular Perfusion and Protects Vital Organs.","authors":"Carlos J Munoz, Daniela Lucas, Ivan S Pires, Thekla Cordes, Cynthia Muller, Krianthan Govender, Amanda Breton, Christian M Metallo, Andre F Palmer, Pedro Cabrales","doi":"10.1097/SHK.0000000000002636","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002636","url":null,"abstract":"<p><strong>Introduction: </strong>Low titer O positive Whole Blood (LTOWB) has been introduced in prehospital care to resuscitate patients; however, the logistical obstacles, cost of carrying LTOWB, and the availability of it in trauma situations are a point of concern. Therefore, fluids, like Lactated Ringer's (LR) and hydroxyethyl starch (HES) have been considered alternatives to LTOWB transfusion. Unfortunately, they dilute plasma proteins in the circulation and have unfavorable side effects. This study presents an alternative, a Protein Cocktail (PC). The PC combines human serum albumin, transferrin, haptoglobin, and hemopexin. This study compares the ability to resuscitate from hemorrhagic shock (HS) with Whole Blood (WB), LR, 6% HES, and PC.</p><p><strong>Methods: </strong>Unanesthetized Golden Syrian hamsters instrumented with the dorsal window chambers were subjected to hemorrhage (50% blood volume), followed by 30 min hypovolemic shock, and resuscitated with 50% shed volume. The outcome was evaluated through systemic parameters, blood gases, microcirculatory hemodynamics, oxygen tension and saturation, metabolomics, and markers of organ injury/function. Additionally, to investigate the impact of the experimental solutions on the coagulation cascade, Sprague Dawley rats were subjected to an isovolemic exchange-infusion of 20% of the animal's blood volume.</p><p><strong>Results: </strong>The PC showed favorable outcomes, restoring microvasculature hemodynamics comparable to resuscitation with Whole Blood and superior to Lactated Ringer's and HES. PC reduced acute inflammation, positively impacted organ function markers, and restore metabolomic homeostasis without coagulopathies observed with HES.</p><p><strong>Conclusion: </strong>In conclusion, the Protein Cocktail (PC) shows some promise as a resuscitation from hemorrhagic shock when Whole Blood is not available, and superior to classic crystalloids and colloids (LR and HES). Further studies with the PC are needed to ensure its efficacy and safety in other experimental models.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476647","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 Gut Microbiota Alterations on Mitochondrial Bioenergetics in Cortical Astrocytes and Sensorimotor Impairment in a Rat Model of Lipopolysaccharide-Associated Encephalopathy.","authors":"Chun-Ta Huang, Ying-Chou Wang, Shih-Chang Lin, Yen-Chi Lai, Seu-Hwa Chen, Shu-Ting Feng, Yi-Ju Tsai","doi":"10.1097/SHK.0000000000002637","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002637","url":null,"abstract":"<p><strong>Purpose: </strong>Brain dysfunction is a significant complication of sepsis, commonly referred to as sepsis-associated encephalopathy (SAE). Alterations in gut microbiota during sepsis may contribute to development of SAE through the gut-brain axis. This study investigated effects of fecal transplantation from healthy or endotoxemic individuals on gut microbiota and brain function in a rat model of lipopolysaccharide (LPS)-associated encephalopathy.</p><p><strong>Methods: </strong>Following LPS induction, rats received daily oral gavage of fecal microbiota transplants for three days. Sensory and motor functions were assessed daily throughout the seven-day study period after LPS exposure. On day seven post-LPS, the study examined gut microbiota structure and composition, serum and fecal short-chain fatty acids (SCFAs) levels, ileal villus length, intestinal permeability, neuronal and glial ultrastructure, cytokine concentrations (pro-inflammatory and anti-inflammatory), and mitochondrial bioenergetics.</p><p><strong>Results: </strong>Administration of healthy donor feces preserved gut microbial structure and composition, maintained ileal villus length, and improved intestinal permeability following LPS treatment. Additionally, it increased SCFA levels, reduced pro-inflammatory cytokines, enhanced anti-inflammatory cytokine release, and restored sensitivity to mechanical and thermal stimuli, as well as motor function. Rats treated with healthy donor feces also exhibited reduced neuronal necrosis and a decreased density of mitochondria in cortical astrocytes. Notably, mitochondrial metabolism in LPS-treated rats returned to near-normal levels following treatment with healthy donor feces. In contrast, administration of endotoxemic donor feces exacerbated these effects in LPS-treated rats.</p><p><strong>Conclusion: </strong>Ameliorating gut dysbiosis prevents mitochondrial dysfunction in astrocytes by promoting SCFA production and enhancing anti-inflammatory cytokine release. This process preserves neuronal integrity and mitigates the severity of encephalopathy.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476644","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":"Exosomes isolated from blood induce acute lung injury in a rat septic peritonitis model.","authors":"Hiroshi Kono, Shinji Furuya, Hidetake Amemiya, Naohiro Hosomura, Daisuke Ichikawa","doi":"10.1097/SHK.0000000000002658","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002658","url":null,"abstract":"<p><strong>Aim: </strong>Acute lung injury (ALI) is a common cause of morbidity in patients with severe sepsis. Exosomes (EXOs) have been reported to induce ALI after severe hemorrhagic shock; therefore, this study aimed to investigate the role of EXOs isolated from the blood of septic rats with ALI.</p><p><strong>Materials and methods: </strong>Blood samples and lung tissues were collected from rats undergoing cecal ligation and puncture (CLP). EXOs were isolated by centrifugation from the blood of rats undergoing CLP and administered intravenously to normal rats, and 12 h after administration, lung tissues were harvested. Pathophysiological changes in the lung, the lung wet/dry weight ratio, and the lung microvascular permeability were assessed. Plasma inflammatory cytokines, namely tumor necrosis factor (TNF)-a, interleukin-6, and high-mobility group box chromosomal protein 1, were measured by enzyme-linked immunosorbent assay. In addition, lung microthrombosis was evaluated by immunohistochemistry. To investigate the effects of EXOs on tissue macrophages (Mfs), the production of TNF-a by isolated tissue Mfs was assessed in the presence or absence of EXOs in vitro.</p><p><strong>Results: </strong>Interstitial pulmonary edema, inflammatory cell infiltration, microhemorrhage, and microthrombosis were observed in the lung after CLP. Similar pathophysiological changes were observed in normal rats administered EXOs, although the extent of these changes was less severe than that in rats undergoing CLP. After EXO administration, the lung wet/dry ratio, lung microvascular permeability, and plasma inflammatory cytokine levels increased. The production of TNF-a by tissue Mfs increased during coculture with EXOs, blocked by anti-toll-like receptor 4 antibodies in the media. Furthermore, TNF-a production significantly decreased in EXO-stimulated cells treated with Triton X or proteinase K, suggesting that the surface protein and lipid fraction were most likely primary determinants.</p><p><strong>Conclusion: </strong>EXOs isolated from the blood of septic rats trigger ALI by increasing inflammatory mediators.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476565","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":"Pulmonary and Extrapulmonary Effects of Prolonged Prone Positioning in a Porcine Model of Acute Respiratory Distress Syndrome.","authors":"Yi Bian, Qian-Rui Huang, Ying-Fang Zheng, Ting-Ting Xu, Jian-Feng Xu, Jie Xiong, Wei-Wei Shang, Chun-Ling Guo, Yong-Qiang Zhang, Mei He, Fang-Fang Li, Dan-Li Zheng, Lin Hu, Hang Ruan, Qi Meng, Jin-Long Luo, Song-Qiao Liu, Shu-Sheng Li","doi":"10.1097/SHK.0000000000002649","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002649","url":null,"abstract":"<p><strong>Background: </strong>Prone positioning (PP) improves survival in severe acute respiratory distress syndrome (ARDS), but its prolonged effects on pulmonary and extrapulmonary organs remain unclear. This study aimed to investigate the pathophysiological effects of 24-hour PP in a porcine ARDS model.</p><p><strong>Methods: </strong>Ten female Bama mini swine (49.5 ± 3.7 kg) underwent severe ARDS induction via repeated saline lavage and were randomized to PP (n = 5) or supine position (SP, n = 5). Respiratory parameters, electrical impedance tomography (EIT), haemodynamics, and biochemical serum analysis were performed. After 24 hours, regional lung injury was assessed via histopathology and wet-dry weight (W/D) ratio, and extrapulmonary injury was evaluated by histopathology, apoptosis, oxidative stress, and organ-specific injury biomarkers.</p><p><strong>Results: </strong>Nine swine were analyzed (PP, n = 5; SP, n = 4). PP significantly improved the PaO2/FiO2 ratio. EIT showed sustained improvements in ventilation, perfusion, and ventilation-perfusion matching (V/Q matching), particularly in the dorsal regions. W/D ratio in the dorsal lung was significantly lower in the PP group, with no significant differences in respiratory mechanics or histopathological lung injury. Haemodynamic parameters, intra-abdominal pressure, and serum biochemical analyses showed no significant differences. Extrapulmonary injury analysis revealed no differences, except for a higher apoptotic index in renal tissue in the PP group.</p><p><strong>Conclusions: </strong>Prolonged PP improved oxygenation by improving ventilation, perfusion, and V/Q matching, while reducing dorsal lung edema, without significantly affecting respiratory mechanics or histopathological lung injury. Additionally, PP showed no significant damage on haemodynamics and extrapulmonary organ function. However, attention should be given to potential renal impairment during prolonged PP administration.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476646","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":"Activation of intestinal mast cells contributes to gut damage after cardiac arrest in mice.","authors":"Lihong Dang, Ata Ur Rehman, Jin Zhang, Ran Zhang, Xinyuan Yu, Huaxin Sheng, Jörn Karhausen, Wei Yang","doi":"10.1097/SHK.0000000000002640","DOIUrl":"10.1097/SHK.0000000000002640","url":null,"abstract":"<p><strong>Abstract: </strong>Sudden cardiac arrest (CA) is associated with high mortality and morbidity rates, largely due to detrimental effects of global ischemia on every organ. Notably, clinical evidence indicates that gastrointestinal tract damage is frequently observed in successfully resuscitated CA patients and suggests that this damage has a negative impact on prognosis. However, experimental CA studies have rarely examined this clinically relevant pathologic change and as such, little is known about the underlying mechanisms. Here, we provide the first evidence that mast cells (MCs) play a critical role in gut damage after CA. Our data first showed notable activation of intestinal MCs and evidence of disrupted gut integrity following CA in a mouse model. Then, using both pharmacologic and genetic tools, we found that treatment with the MC activator C48/80 significantly increased gut permeability, while gut function was better preserved in MC-deficient mice compared to wild-type mice. Together, our results identified MC activation as a critical pathologic process driving post-CA gut damage.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12324823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643348","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}