SHOCKPub Date : 2024-12-16DOI: 10.1097/SHK.0000000000002541
Alen Palackic, Amina El Ayadi, Charles E Wade, Lisa A Baer, Ludwik K Branski, Gabriel Hundeshagen, Julia Kleinhapl, Steven E Wolf, Juquan Song
{"title":"Combined Effects of Oxandrolone and Exercise on Muscle Recovery in Rats with Severe Burn and Hindlimb Unloading.","authors":"Alen Palackic, Amina El Ayadi, Charles E Wade, Lisa A Baer, Ludwik K Branski, Gabriel Hundeshagen, Julia Kleinhapl, Steven E Wolf, Juquan Song","doi":"10.1097/SHK.0000000000002541","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002541","url":null,"abstract":"<p><strong>Background: </strong>Loss of muscle mass and strength in patients who have experienced severe burns is dramatic and associated with subsequent functional impairment. Past work has shown that exercise and oxandrolone, an anabolic steroid, individually improve muscle function and muscle mass in severely burned patients. This study aims to evaluate the effect of oxandrolone treatment combined with resistance exercise on muscle atrophy and investigate the protein synthesis and mitochondrial biogenesis pathways in a hindlimb suspension model.</p><p><strong>Methods: </strong>Twenty-four Sprague Dawley rats received 40% total body surface area (%TBSA) scald burns and were then placed for hindlimb unloading. All animals were randomly grouped into vehicle (corn oil) without exercise (V/NEX), oxandrolone administration (0.1 mg/kg/day) without exercise (OX/NEX), vehicle with exercise (V/EX), or oxandrolone with exercise (OX/EX). (n = 6/group). On day 14 isometric forces of the left plantaris and soleus muscle were measured by using a muscle lever system with dynamic muscle control and analysis software. Fatigue measurement was only performed in the soleus muscle. The tissue of the muscle was then collected for protein extraction. Western blots were performed to study signal alternations and mitochondrial biogenesis pathways.</p><p><strong>Results: </strong>Tetanic force (Po) was significantly increased in the plantaris with exercise, rather than with oxandrolone treatment. Fatigue index (FI) was lower and integration was significantly elevated in the soleus with exercise but not with oxandrolone treatment. Fatigue curve in the soleus further revealed the average maximum force were achieved in soleus with either oxandrolone treatment or exercise alone independently. Raptor and p-Akt levels are elevated in the OX/EX group while PGC1a expression was not altered.</p><p><strong>Conclusion: </strong>Oxandrolone and resistance exercise have independent positive effects on muscle function recovery in this clinically relevant rodent model of severe burn. Both treatments combined increased signaling pathways by increasing protein synthesis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922129","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}
SHOCKPub Date : 2024-12-10DOI: 10.1097/SHK.0000000000002535
Xiaoke Wang, Xiaojuan Fan, Taibo Wu, Shaopeng Che, Xue Shi, Peining Liu, Junhui Liu, Yongbai Luo, Yue Wu, Beidi Lan
{"title":"A Clinical Prediction Model For Short-Term Prognosis In Patients With Non Acute Myocardial Infarction Related Cardiogenic Shock.","authors":"Xiaoke Wang, Xiaojuan Fan, Taibo Wu, Shaopeng Che, Xue Shi, Peining Liu, Junhui Liu, Yongbai Luo, Yue Wu, Beidi Lan","doi":"10.1097/SHK.0000000000002535","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002535","url":null,"abstract":"<p><strong>Background: </strong>While acute myocardial infarction (AMI) is widely recognized as the primary cause of Cardiogenic Shock (CS), Non-AMI related CS has been excluded from the majority of CS studies. Information on its prognostic factors remains largely understudied, and it is necessary to focus on these patients to identify the specific risk factors. In this study, we aimed to build and validate a predictive nomogram and risk classification system.</p><p><strong>Methods: </strong>1298 patients and 548 patients with CS from the Medical Information Mart for Intensive Care IV (MIMIC-IV) and MIMIC-III databases were included in the study after excluding patients with acute myocardial infarction. Lasson and logistic regression analysis were used to identify statistically significant predictors which were finally involved in the nomogram. The predictive performance of the nomogram was validated by calibration plots and was compared with other scoring systems by AUC and DCA curves.</p><p><strong>Results: </strong>Age, heart rate, WBC count, albumin level, lactic acid level, GCS Score, 24 h urine output, and vasopressor use were identified as the most critical factors for in-hospital death. Based on these results, a nomogram was established for predicting in-hospital mortality. The AUC value of the nomogram was 0.806 in the training group and 0.814 and 0.730 in the internal and external validation sets, respectively, which were significantly higher than those of other commonly used Intensive Care Unit scoring systems (SAPSII, APSIII, and SOFA).In addition, the survival curve showed significant differences in the 30-day survival of the three risk subgroups divided by the nomogram.</p><p><strong>Conclusion: </strong>For non-AMI associated CS, a predictive nomogram and risk classification system were developed and validated, and the nomogram demonstrated good performance in prognostic prediction and risk stratification.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814215","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}
SHOCKPub Date : 2024-12-05DOI: 10.1097/SHK.0000000000002533
Stéphane Bar, John Diaper, Fabienne Fontao, Xavier Belin, Stanislas Abrard, Gergely Albu, Hervé Dupont, Walid Habre, Eduardo Schiffer
{"title":"Early and concomitant administration of norepinephrine and ilomedin improves microcirculatory perfusion without impairing macrocirculation in an intestinal ischemia-reperfusion injury swine model : a randomized experimental trial.","authors":"Stéphane Bar, John Diaper, Fabienne Fontao, Xavier Belin, Stanislas Abrard, Gergely Albu, Hervé Dupont, Walid Habre, Eduardo Schiffer","doi":"10.1097/SHK.0000000000002533","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002533","url":null,"abstract":"<p><strong>Background: </strong>Intestinal ischemia-reperfusion injury is associated with both macrocirculatory and microcirculatory failure. Association of a vasoconstrictor in combination with a vasodilator such as ilomedin may improve macrocirculation parameters, microcirculation perfusion and reduce endothelial dysfunction. The primary objective was to demonstrate a difference in mean arterial pressure (MAP) after intestinal reperfusion with the concomitant administration of norepinephrine and ilomedin during ischemia compared with traditional hemodynamic treatment strategies (fluid resuscitation and vasopressors only). Secondary objectives were to demonstrate an improvement in peripheral and intestinal microcirculatory perfusion and endothelial dysfunction after intestinal reperfusion using this association.</p><p><strong>Methods: </strong>We conducted a randomized preclinical trial in twenty-one large white pigs, in which a 2-hour small bowel ischemia was performed using a segmental mesenteric occlusion model, followed by a 2-hour reperfusion. Pigs were randomized into 3 groups: goal directed fluid therapy, early administration of norepinephrine before reperfusion and early administration of ilomedin and norepinephrine before reperfusion. Macrocirculatory (MAP and Cardiac Index (CI)), microcirculatory (Sublingual with SideStream Dark Field system and intestinal hemoglobin oxygen saturation with hyperspectral imaging (HSI)) measurements and biological analysis (biomarkers of endothelial dysfunction) were performed.</p><p><strong>Results: </strong>There were no significant differences in the MAP (p = 0.499) and the CI (p = 0.659) between the 3 groups. Perfused Vessel Density (PVD) in sublingual microcirculation was significantly higher immediately after reperfusion and 2 hours after reperfusion in the early administration of ilomedin and norepinephrine group compared with the other 2 groups (p < 0.05). Hemoglobin oxygen saturation measured at the intestinal level was significantly higher immediately after reperfusion in the early administration of ilomedin and norepinephrine group compared with the other 2 groups (p < 0.01). There were no significant differences in biomarkers of endothelial dysfunction between the 3 groups. Creatinine, AST and alkaline phosphatases increased significantly 2 hours after reperfusion in the early administration of ilomedin and norepinephrine group compared with baseline (p < 0.05).</p><p><strong>Conclusions: </strong>Early administration of norepinephrine and ilomedin during ischemia improved short-term post-reperfusion sublingual and intestinal microcirculation without worsening macrocirculatory parameters in an intestinal ischemia-reperfusion injury model. However, use of this strategy seemed to worsen both liver and kidney function.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786939","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}
SHOCKPub Date : 2024-12-03DOI: 10.1097/SHK.0000000000002514
Jian Guo, Huiheng Qu, Peng Cui, Yu Xue
{"title":"USP33 promotes caerulein-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":"https://doi.org/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: Caerulein-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: Caerulein 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 caerulein-induced HPDE6-C7 cells (3.3 ±0.34 vs. 1.0 ±0.10, P < 0.05). Knockdown of TRAF3 protected HPDE6-C7 cells from caerulein-induced apoptotic, oxidative and inflammatory injuries. Mechanistically, USP33 interacted with TRAF3 and induced TRAF3 deubiquitination to up-regulate its expression (P < 0.05). Further analyses showed that USP33 knockdown reversed caerulein-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 caerulein-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":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-03","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}
SHOCKPub Date : 2024-12-03DOI: 10.1097/SHK.0000000000002516
Ze Long, Shengzhi Tan, Baisheng Sun, Yong Qin, Shengjie Wang, Zhencan Han, Tao Han, Feng Lin, Mingxing Lei
{"title":"Predicting In-Hospital Mortality in Critical Orthopaedic Trauma Patients with Sepsis Using Machine Learning Models.","authors":"Ze Long, Shengzhi Tan, Baisheng Sun, Yong Qin, Shengjie Wang, Zhencan Han, Tao Han, Feng Lin, Mingxing Lei","doi":"10.1097/SHK.0000000000002516","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002516","url":null,"abstract":"<p><strong>Abstract: </strong>Purpose: This study aims to establish and validate machine learning-based models to predict death in hospital among critical orthopaedic trauma patients with sepsis or respiratory failure.Methods: This study collected 523 patients from the Medical Information Mart for Intensive Care database. All patients were randomly classified into a training cohort and a validation cohort. Six algorithms, including logistic regression (LR), extreme gradient boosting machine (eXGBM), support vector machine (SVM), random forest (RF), neural network (NN), and decision tree (DT), were used to develop and optimize models in the training cohort, and internal validation of these models were conducted in the validation cohort. Based on a comprehensive scoring system, which incorporated ten evaluation metrics, the optimal model was obtained with the highest scores. An artificial intelligence (AI) application was deployed based on the optimal model in the study.Results: The in-hospital mortality was 19.69%. Among all developed models, the eXGBM had the highest area under the curve (AUC) value (0.951, 95%CI: 0.934-0.967), and it also showed the highest accuracy (0.902), precise (0.893), recall (0.915), and F1 score (0.904). Based on the scoring system, the eXGBM had the highest score of 53, followed by the RF model (43) and the NN model (39). The scores for the LR, SVM, and DT were 22, 36, and 17, respectively. The decision curve analysis confirmed that both the eXGBM and RF models provided substantial clinical net benefits. However, the eXGBM model consistently outperformed the RF model across multiple evaluation metrics, establishing itself as the superior option for predictive modeling in this scenario, with the RF model as a strong secondary choice. The SHAP analysis revealed that SAPS II, age, respiratory rate, OASIS, and temperature were the most important five features contributing to the outcome.Conclusions: This study develops an artificial intelligence application to predict in-hospital mortality among critical orthopaedic trauma patients with sepsis or respiratory failure.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786999","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}
SHOCKPub Date : 2024-12-03DOI: 10.1097/SHK.0000000000002531
Tetsuya Yumoto, Takehiko Oami, Zhe Liang, Eileen M Burd, Mandy L Ford, Jerrold R Turner, Craig M Coopersmith
{"title":"Intestinal epithelial-specific occludin deletion worsens gut permeability and survival following sepsis.","authors":"Tetsuya Yumoto, Takehiko Oami, Zhe Liang, Eileen M Burd, Mandy L Ford, Jerrold R Turner, Craig M Coopersmith","doi":"10.1097/SHK.0000000000002531","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002531","url":null,"abstract":"<p><strong>Abstract: </strong>Sepsis induces intestinal hyperpermeability, which is associated with higher mortality. Occludin is a tight junction protein that plays a critical role in regulating disease-associated intestinal barrier loss. This study examined the role of intestinal occludin on gut barrier function and survival in a pre-clinical model of sepsis. Intestinal epithelial-specific occludin knockout (occludin KOIEC) mice and wild type controls were subjected to intra-abdominal sepsis and sacrificed at pre-determined endpoints for mechanistic studies or followed for survival. Occludin KOIEC mice had a significant increase in intestinal permeability, that was induced only in the setting of sepsis as knockout mice and control mice had similar baseline permeability. The worsened barrier was specific to the leak pathway of permeability, without changes in either the pore or unrestricted pathways. Increased sepsis-induced permeability was associated with increased levels of the tight junction ZO-1 in occludin KOIEC mice. Occludin KOIEC mice also had significant increases in systemic cytokines IL-6 and MCP-1and increased bacteremia. Further, occludin KOIEC mice had higher levels of jejunal IL-1β and MCP-1 as well as increased MCP-1 and IL-17A in the peritoneal fluid although peritoneal bacteria levels were unchanged. Notably, 7-day mortality was significantly higher in occludin KOIEC mice following sepsis. Occludin thus plays a critical role in preserving gut barrier function and mediating survival during sepsis, associated with alterations in inflammation and bacteremia. Agents that preserve occludin function may represent a new therapeutic strategy in the treatment of sepsis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786977","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}
SHOCKPub Date : 2024-12-01Epub Date: 2024-10-29DOI: 10.1097/SHK.0000000000002485
Chongxiao Xu, Bingling Yin, Yueli Zhao, Haiyang Guo, Xiaogan Hou, Anwei Liu, Xuan He, Wenda Chen, Guodong Lin, Zhiguo Pan
{"title":"A NOMOGRAM BASED ON THE VALUE OF THE DYNAMIC EVOLUTION OF SYSTEMIC IMMUNE INFLAMMATORY INDEX IN THE EVALUATION OF SEVERE HEATSTROKE.","authors":"Chongxiao Xu, Bingling Yin, Yueli Zhao, Haiyang Guo, Xiaogan Hou, Anwei Liu, Xuan He, Wenda Chen, Guodong Lin, Zhiguo Pan","doi":"10.1097/SHK.0000000000002485","DOIUrl":"10.1097/SHK.0000000000002485","url":null,"abstract":"<p><strong>Abstract: </strong>Background : Severe heatstroke patients have a poor prognosis. There are few descriptions of the inflammatory response to heatstroke in clinical studies. Systemic immune-inflammation index (SII) is a new index to reflect the inflammatory state of disease. Methods : This retrospective observational study included patients who had severe heatstroke between 2010 and 2023. Multivariate logistic regression and nomogram were performed to determine the ability of the SII to predict the prognosis of these patients, and subgroup analysis was performed according to SII levels. Results : Of the 177 patients included in our study, 28 (15.8%) died. There was no difference in SII values between the first day ( P = 0.810) and the second day ( P = 0.184) in multivariate analysis. The SII value of the third day (SII 72) was elevated in patients with heatstroke who died compared to that in those who survived ( P = 0.035). In multivariable logistic regression, Sequential Organ Failure Assessment (SOFA) score (odds ratio [OR], 1.717; confidence interval [CI], 1.073-2.747; P = 0.024) and SII 72 (OR, 1.001; 95% CI, 1.000-1.002; P = 0.035) were found to be independent predictors of mortality. SII 72 combined with SOFA score distinguished between patients who died and those who survived better than did the separate SOFA score. Patients with SII 72 > 1,000 had poor clinical prognosis. Conclusions : Compared to SII results from the first and second days, third-day results more meaningfully predict poor heatstroke prognosis. SII 72 may be a good indicator and, when combined with SOFA, offers enhanced predictive value.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"755-761"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547223","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}
SHOCKPub Date : 2024-12-01Epub Date: 2024-08-13DOI: 10.1097/SHK.0000000000002458
Ryan M Johnson, Kevin E Galicia, Huashan Wang, Richard Gonzalez, Mashkoor Choudhry, John C Kubasiak
{"title":"BURN INJURY RESULTS IN MYELOID PRIMING DURING EMERGENCY HEMATOPOIESIS.","authors":"Ryan M Johnson, Kevin E Galicia, Huashan Wang, Richard Gonzalez, Mashkoor Choudhry, John C Kubasiak","doi":"10.1097/SHK.0000000000002458","DOIUrl":"10.1097/SHK.0000000000002458","url":null,"abstract":"<p><strong>Abstract: </strong>Introduction: Hematopoiesis proceeds in a tiered pattern of differentiation, beginning with hematopoietic stem cells (HSC) and culminating in erythroid, myeloid, and lymphoid lineages. Pathologically altered lineage commitment can result in inadequate leukocyte production or dysfunctional cell lines. Drivers of emergency hematopoiesis after burn injury are inadequately defined. Burn injury induces a myeloid predominance associated with infection that worsens outcomes. This study aims to further profile bone marrow HSCs following burn injury in a murine model. Methods: C57BL/6 mice received burn or sham injury with ~12% total body surface area scald burn on the dorsal surface with subsequent sacrifice at 1, 2, 3, 7, and 10 days postinjury. Bone marrow from hindlimbs was analyzed for HSC populations via flow cytometry and analyzed using FlowJo Software (version 10.6). Event counts and frequencies were analyzed with multiple unpaired t tests and linear mixed-effect regression. Real-time polymerase chain reaction performed on isolated lineage-negative bone marrow cell RNA targeted PU.1, GATA-1, and GATA-3 with subsequent analysis conducted with QuantStudio 3 software. Statistical analysis and representation were performed on GraphPad software (Prism). Results: Flow cytometry revealed significantly elevated proportions of long-term HSCs at 3 days post-injury ( P < 0.05) and short-term HSCs at days 2, 3, and 10 (all P < 0.05) in burn-injured mice. There was a sustained, but not significant, increase in proportions in the multipotent progenitor (MPP) 2 and 3 subpopulations in the burn cohort compared to sham controls. The common myeloid progenitor (CMP) proportion was significantly higher on days 3 and 10 (both P < 0.01), whereas the granulocyte-macrophage progenitor (GMP) proportion increased on days 1, 2, and 10 ( P < 0.05, P < 0.01, P < 0.01, respectively). Although the megakaryocyte-erythrocyte progenitor (MEP) proportion appeared consistently lower in the burn cohort, this did not reach significance. mRNA analysis resulted in a downregulation of PU.1 on day 1 ( P = 0.0002) with an upregulation by day 7 ( P < 0.01). GATA-1 downregulation occurred by day 7 ( P < 0.05), and GATA3 showed downregulation on days 3 and 7 ( P < 0.05). Discussion: Full-thickness burn results in an emergency hematopoiesis via proportional increase of long-term HSC and short-term HSC/MPP1 subpopulations beginning in the early postinjury period. Subsequent lineage commitment displays a myeloid predominance with a shift toward myeloid progenitors with mRNA analysis corroborating this finding with associated upregulation of PU.1 and downregulation of GATA-1 and GATA-3. Further studies are needed to understand how burn-induced emergency hematopoiesis may predispose to infection by pathologic lineage selection.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"783-789"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073812","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}
SHOCKPub Date : 2024-12-01Epub Date: 2024-05-30DOI: 10.1097/SHK.0000000000002408
Hui Liu, Wei Xiong, Wu Zhong, Yingchun Hu
{"title":"NOVEL ACTIVE PROTEINS FOR SEPSIS PROGNOSIS REVEALED THROUGH ScRNA-seq AND QUANTITATIVE PROTEOMICS.","authors":"Hui Liu, Wei Xiong, Wu Zhong, Yingchun Hu","doi":"10.1097/SHK.0000000000002408","DOIUrl":"10.1097/SHK.0000000000002408","url":null,"abstract":"<p><strong>Abstract: </strong>Objective: To uncover critical active proteins influencing sepsis outcomes through multiomics analysis. Methods: This study collected peripheral blood from sepsis patients (NS = 26, SV = 27) and controls (Con = 16). Cellular heterogeneity was assessed using scRNA-seq. Cellular populations were identified through clustering and annotation. Gene set variation analysis was employed to detect pathway alterations in sepsis, while the Viper algorithm estimated protein activity at the single-cell level. Signaling networks were investigated via cell-cell communication analysis. Differentially expressed proteins were identified by DIA proteomics and confirmed through integrated analysis. Prognostic value was evaluated via meta and survival analyses. Results: scRNA-seq of 22,673 features within 34,228 cells identified five cellular clusters and 253 active proteins via Viper, validated by DIA (FC > 2, P < 0.05). Four proteins (SPI1, MEF2A, CBX3, UBTF) with prognostic significance were discovered and mapped onto the cellular landscape. Gene set variation analysis enrichment analysis revealed that the NS group exhibited significant alterations in pathways related to cellular apoptosis and inflammatory responses, while the SV group displayed increased activity in DNA repair and cellular survival pathways. Conclusion: The study's findings advance the understanding of sepsis pathophysiology by linking differentially active proteins to patient prognosis, paving the way for targeted therapeutic strategies.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"738-745"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420673","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}