HMGB1 released from pyroptotic vascular endothelial cells promotes immune disorders in exertional heatstroke.

BACKGROUND AND OBJECTIVE: Exertional heatstroke (EHS) mainly occurs in healthy young people with rapid onset and high mortality. EHS immune disorders can cause systemic inflammatory responses and multiple organ failure; however, the underlying mechanisms remain unclear. As high mobility group box 1 (HMGB1) is a prototypical alarmin that activates inflammatory and immune responses, this study aimed to investigate the effect and mechanism of HMGB1 in the pathogenesis of EHS. METHODS: Peripheral blood mononuclear cell (PBMC) transcriptome sequencing of healthy volunteers, classical heatstroke patients, and EHS patients was performed. A mouse model of EHS was established and murine tissue damage was evaluated by H&E staining. HMGB1 localization and release were visualized using immunofluorescence staining. Human umbilical vein endothelial cells (HUVECs) and THP-1 cells were co-cultured to study the effects of HMGB1 on macrophages. A neutralizing anti-HMGB1 antibody was used to evaluate the efficacy of EHS treatment in mice. RESULTS: Plasma and serum HMGB1 levels were significantly increased in EHS patients or mice. EHS-induced endothelial cell pyroptosis promoted HMGB1 release in mice. HMGB1 derived from endothelial cell pyroptosis enhanced macrophage pyroptosis, resulting in immune disorders under EHS conditions. Administration of anti-HMGB1 markedly alleviated tissue injury and systemic inflammatory responses after EHS. CONCLUSIONS: The release of HMGB1 from pyroptotic endothelial cells after EHS promotes pyroptosis of macrophages and systemic inflammatory response, and HMGB1-neutralizing antibody therapy has good application prospects for EHS.

Gram-negative bacterial infection causes aggravated innate immune response in sepsis: Studies from clinical samples and cellular models.

Bacterial infection is the most common cause for sepsis. The purpose of this study was to evaluate the impact of different bacterial infection on sepsis based on human samples and cellular experiments. Physiological indexes and prognostic information of 121 sepsis patients were analysed based on whether they had a gram-positive or gram-negative bacterial infection. Moreover, murine RAW264.7 macrophages were treated with lipopolysaccharide (LPS) or peptidoglycan (PG) to simulate infection with gram-negative or gram-positive bacteria in sepsis, respectively. Exosomes derived from the macrophages were extracted for transcriptome sequencing. In patients with sepsis, most gram-positive bacterial infections were Staphylococcus aureus, and gram-negative infections were Escherichia coli. Gram-negative bacterial infection was significantly associated with high neutrophil and interleukin (IL)-6 levels in blood and shorter prothrombin (PT) and activated partial thromboplastin time (APTT). Intriguingly, the survival prognosis of sepsis patients was not affected by the type of bacterial infection, but it was significantly related to fibrinogen. Protein transcriptome sequencing of the macrophage-derived exosomes showed that differentially expressed proteins were significantly enriched in megakaryocyte differentiation, leukocyte and lymphocyte-mediated immunity, and complement and coagulation cascade pathways. The complement and coagulation-related proteins were significantly upregulated after LPS induction, which explained the shortened PT and APTT in gram-negative bacterial sepsis. Bacterial infection did not affect mortality in sepsis but did alter the host response. The immune disorder induced by gram-negative infection was more severe than that produced by gram-positive infection. This study provides references for the rapid identification and molecular research of different bacterial infections in sepsis.

Identification of hub genes and potential inhibitory compounds in the process of liver transplantation through transcriptome sequencing.

Liver transplantation (LT) is the best choice for patients with end-stage liver diseases. In order to better understand pathophysiological alterations in LT, we aimed to identify potential hub genes and inhibitory compounds involved in the LT process. Four pairs of peripheral blood mononuclear cell (PBMC) samples of the LT recipients before and after surgery were collected and taken for transcriptome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the screened differentially expressed genes (DEGs) between pre- and post-operation groups. Common DEGs were obtained from GO and KEGG enriched pathways, followed by protein-protein interaction (PPI) network construction, hub gene identification, module analysis, and structure-based virtual screening process (SBVS). Compared to the pre-operation stage, 4745 genes were down-regulated and 798 up-regulated after LT. GO analysis showed that the DEGs were enriched in ribosome-related translation regulation, and KEGG analysis indicated that infection and immune-related pathways and diseases were largely enriched. A large number of down-regulated DEGs were not only associated with ribosome-related pathways but also with the alterations of epigenetic modifications, in particular ubiquitination. Moreover, through the PPI network of 29 common genes from GO and KEGG-enriched pathways, 7 hub genes were identified, including PTEN, MYC, EIF2S1, EIF4EBP1, HSP90AB1, TP53, and HSPA8, which were mainly involved in the PI3K-AKT signaling pathway. SBVS of the seed molecule PTEN (PDB code: 1D5R) predicted top hits compounds that may serve as potential inhibitors of PTEN, of which the compound ZINC4235331 had the lowest binding affinity of -10 kcal/mol. The significance of screened hub genes and potential inhibitors involved in the process of LT provides novel therapeutic strategies for improving the outcomes of LT recipients during surgery.

HIF-1α promotes the expression of syndecan-1 and inhibits the NLRP3 inflammasome pathway in vascular endothelial cells under hemorrhagic shock.

Hemorrhagic shock (HS) is a global life-threatening matter that causes massive mortality annually worldwide. Syndecan-1 (SDC1) is an important predictor and evaluation index for HS, but its mechanism involved in the HS development remain unclear. HS mice model and human umbilical vein endothelial cells (HUVECs) under hypoxia were applied to explore the relationship of SDC1 with HIF-1α and NLRP3 inflammasome in vascular ECs under HS. Transcriptome sequencing of isolated vascular ECs were conduct to search for hub genes. Dual luciferase assay was adopted to prove the binding effects of the HIF-1α on SDC1 promoter in HUVECs. Molecular expression was evaluated through routine experiments. Here, HS led to aggravated lung injury and inflammatory response with the shedding of SDC1 on the lung vascular ECs in mice. Circulatory SDC1 and proinflammatory cytokines were significantly increased after HS. HIF-1α and IL-1ß were identified as hub genes in vascular ECs of HS mice. Meanwhile, HIF-1α-mediaed hypoxia and IL-1ß-involved NLRP3 inflammasome pathways were activated following HS. The transcriptional factor HIF-1α promoted the expression of SDC1 through binding to the SDC1 promoter. SDC1 had an inhibitory effect on the NLRP3 inflammasome activity. An exogenous increase of HIF-1α upregulated SDC1 and restrained the activation of the NLRP3 inflammasome under hypoxia, while further interference of SDC1 weakened this effect. Hence, SDC1 is an intermediate connecting HIF-1α and NLRP3 inflammasome in the vascular ECs under hypoxia. HIF-1α promotes the expression of SDC1 and inhibits the NLRP3 inflammasome pathway in vascular ECs under HS.

Long non-coding RNA NEAT1 promotes lipopolysaccharide-induced injury in human tubule epithelial cells by regulating miR-93-5p/TXNIP axis.

Many long non-coding RNAs (lncRNAs) have been found to play crucial roles in sepsis-induced acute kidney injury (AKI), including lncRNA nuclear-enriched abundant transcript 1 (NEAT1). We aimed to further elucidate the functions and molecular mechanism of NEAT1 in sepsis-induced AKI. Sepsis-induced AKI cell model was established by treatment with lipopolysaccharide (LPS) in human tubule epithelial (HK2) cells. Cell viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Western blot assay was performed to measure all protein levels. The concentrations of inflammatory factors were evaluated using enzyme-linked immunosorbent assay (ELISA). The expression levels of inflammatory factors, NEAT1, microRNA-93-5p (miR-93-5p), and thioredoxin-interacting protein (TXNIP) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The oxidative stress factors were detected using corresponding kits. The interaction between miR-93-5p and NEAT1 or TXNIP was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. NEAT1 was upregulated in serum of sepsis patients and LPS-induced HK2 cells. NEAT1 silence alleviated LPS-induced HK2 cell injury by inhibiting apoptosis, inflammation and oxidative stress. Moreover, miR-93-5p was a direct target of NEAT1, and suppression of NEAT1 weakened LPS-induced injury by upregulating miR-93-5p in HK2 cells. Furthermore, TXNIP was a downstream target of miR-93-5p, and miR-93-5p attenuated LPS-induced HK2 cell injury by downregulating TXNIP. In addition, NEAT1 regulated TXNIP expression by acting as a sponge of miR-93-5p. NEAT1 might aggravate LPS-induced injury in HK2 cells by regulating miR-93-5p/TXNIP axis, providing a potential therapeutic strategy for sepsis-associated AKI.

ADAR1 attenuates allogeneic graft rejection by suppressing miR-21 biogenesis in macrophages and promoting M2 polarization.

ADAR1 (adenosine deaminase acting on double-stranded RNA 1) is an RNA-editing enzyme that mediates adenosine-to-inosine RNA editing events, an important post-transcriptional modification mechanism that can alter the coding properties of mRNA or regulate microRNA biogenesis. ADAR1 also regulates the innate immune response. Here, we have demonstrated that ADAR1 expression increased in LPS-stimulated macrophages. Silencing ADAR1 by using small interfering RNA in macrophages resulted in the pronounced polarization of macrophages to M1, whereas ADAR1 overexpression promoted M2 polarization, which indicated that ADAR1 can inhibit macrophage hyperpolarization and prevent immune hyperactivity. The RNA-RNP immunoprecipitation binding assay demonstrated a direct interaction between ADAR1 and miR-21 precursor. Significant up-regulation in IL-10 and down-regulation in miR-21 were observed in ADAR1-overexpressing macrophages. We evaluated miR-21 target mRNAs and macrophage polarization signaling pathways and found that forkhead box protein O1 (Foxo1) was up-regulated in cells that overexpressed ADAR1. In a mouse allogeneic skin transplantation model, grafts in the ADAR1-overexpressed group survived longer and suffered less immune cell infiltration. In ADAR1-overexpressed recipients, splenic macrophages were significantly polarized to M2, and levels of sera IL-10 were markedly higher than those in the control group. In summary, ADAR1 modulates macrophage M2 polarization via the ADAR1-miR-21-Foxo1-IL-10 axis, thereby suppressing allogeneic graft rejection.-Li, J., Xie, J., Liu, S., Li, X., Zhang, D., Wang, X., Jiang, J., Hu, W., Zhang, Y., Jin, B., Zhuang, R., Yin, W. ADAR1 attenuates allogeneic graft rejection by suppressing miR-21 biogenesis in macrophages and promoting M2 polarization.

ADAR1 prevents small intestinal injury from inflammation in a murine model of sepsis.

Adenosine deaminase acting on RNA 1 (ADAR1), a double-stranded RNA-editing enzyme that converts adenosine (A) to inosine (I), has been identified as a modulator of immune responses. However, the role of ADAR1 in small intestinal homeostasis during sepsis remains unclear. In this study, we examined the role of ADAR1 on intestinal inflammation in a murine model of sepsis. We found that ADAR1 was highly expressed in "septic" macrophages and small intestinal tissue of septic mice. Deletion of ADAR1 in "septic" macrophages led to rapid apoptosis. In addition, suppression of ADAR1 in "septic" macrophages significantly enhanced inflammation, while over-expression of ADAR1 significantly suppressed the level of inflammatory cytokines. Furthermore, suppression of ADAR1 in septic mice significantly enhanced inflammation and intestinal damage, while enhanced ADAR1 expression resulted in reduced damage and inflammation. Finally, over-expression of ADAR1 improved survival of septic mice. In conclusion, we have identified a novel ADAR1 protective effect for maintaining intestinal homeostasis. Our findings may provide a new targeted therapy for sepsis treatment.

ADAR1 Inhibits Macrophage Apoptosis and Alleviates Sepsis-induced Liver Injury Through miR-122/BCL2A1 Signaling.

Background and Aims: As sepsis progresses, immune cell apoptosis plays regulatory roles in the pathogenesis of immunosuppression and organ failure. We previously reported that adenosine deaminases acting on RNA-1 (ADAR1) reduced intestinal and splenic inflammatory damage during sepsis. However, the roles and mechanism of ADAR1 in sepsis-induced liver injury remain unclear. Methods: We performed transcriptome and single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from patients with sepsis to investigate the effects of ADAR1 on immune cell activities. We also employed a cecal ligation and puncture (CLP) sepsis mouse model to evaluate the roles of ADAR1 in sepsis-induced liver injury. Finally, we treated murine RAW 264.7 macrophages with lipopolysaccharide to explore the underlying ADAR1-mediated mechanisms in sepsis. Results: PBMCs from patients with sepsis had obvious apoptotic morphological features. Single-cell RNA sequencing indicated that apoptosis-related pathways were enriched in monocytes, with significantly elevated ADAR1 and BCL2A1 expression in severe sepsis. CLP-induced septic mice had aggravated liver injury and Kupffer cell apoptosis that were largely alleviated by ADAR1 overexpression. ADAR1 directly bound to pre-miR-122 to modulate miR-122 biosynthesis. miR-122 was an upstream regulator of BCL2A1. Furthermore, ADAR1 also reduced macrophage apoptosis in mice with CLP-induced sepsis through the miR-122/BCL2A1 signaling pathway and protected against sepsis-induced liver injury. Conclusions: The findings show that ADAR1 alleviates macrophage apoptosis and sepsis-induced liver damage through the miR-122/BCL2A1 signaling pathway. The study provides novel insights into the development of therapeutic interventions in sepsis.

Dysregulation of iron transport-related biomarkers in blood leukocytes is associated with poor prognosis of early trauma.

Objective: The early targeted and effective diagnosis and treatment of severe trauma are crucial for patients' outcomes. Blood leukocytes act as significant effectors during the initial inflammation and activation of innate immunity in trauma. This study aims to identify hub genes related to patients' prognosis in blood leukocytes at the early stages of trauma. Methods: The expression profiles of Gene Expression Omnibus (GEO) Series (GSE) 36809 and GSE11375 were downloaded from the GEO database. R software, GraphPad Prism 9.3.1 software, STRING database, and Cytoscape software were used to process the data and identify hub genes in blood leukocytes of early trauma. Results: Gene Ontology (GO) analysis showed that the differentially expressed genes (DEGs) of blood leukocytes at the early stages of trauma (0-4 h, 4-8 h, and 8-12 h) were mainly involved in neutrophil activation and neutrophil degranulation, neutrophil activation involved in immune response, neutrophil mediated immunity, lymphocyte differentiation, and cell killing. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs were mainly involved in Osteoclast differentiation and Hematopoietic cell lineage. Sixty-six down-regulated DEGs and 148 up-regulated DEGs were identified and 37 hub genes were confirmed by Molecular Complex Detection (MCODE) of Cytoscape. Among the hub genes, Lipocalin 2 (LCN2), Lactotransferrin (LTF), Olfactomedin 4 (OLFM4), Resistin (RETN), and Transcobalamin 1 (TCN1) were related to prognosis and connected with iron transport closely. LCN2 and LTF were involved in iron transport and had a moderate predictive value for the poor prognosis of trauma patients, and the AUC of LCN2 and LTF was 0.7777 and 0.7843, respectively. Conclusion: As iron transport-related hub genes in blood leukocytes, LCN2 and LTF can be used for prognostic prediction of early trauma.

ADAR1 protects pulmonary macrophages from sepsis-induced pyroptosis and lung injury through miR-21/A20 signaling.

Acute lung injury is a serious complication of sepsis with high morbidity and mortality. Pyroptosis is a proinflammatory form of programmed cell death that leads to immune dysregulation and organ dysfunction during sepsis. We previously found that adenosine deaminase acting on double-stranded RNA 1 (ADAR1) plays regulatory roles in the pathology of sepsis, but the mechanism of ADAR1 in sepsis-induced pyroptosis and lung injury remains unclear. Here, we mainly investigated the regulatory effects and underlying mechanism of ADAR1 in sepsis-induced lung injury and pyroptosis of pulmonary macrophages through RNA sequencing of clinical samples, caecal ligation and puncture (CLP)-induced septic mouse models, and in vitro cellular experiments using RAW264.7 cells with lipopolysaccharide (LPS) stimulation. The results showed that pyroptosis was activated in peripheral blood mononuclear cells (PBMCs) from patients with sepsis. In the CLP-induced septic mouse model, pyroptosis was mainly activated in pulmonary macrophages. LPS-stimulated RAW264.7 cells showed significantly increased activation of the NLRP3 inflammasome. ADAR1 was downregulated in PMBCs of patients with sepsis, and overexpression of ADAR1 alleviated CLP-induced lung injury and NLRP3 inflammasome activation. Mechanistically, the regulatory effects of ADAR1 on macrophage pyroptosis were mediated by the miR-21/A20/NLRP3 signalling cascade. ADAR1 attenuated sepsis-induced lung injury and hindered the activation of pyroptosis in pulmonary macrophages in sepsis through the miR-21/A20/NLRP3 axis. Our study highlights the role of ADAR1 in protecting pulmonary macrophages against pyroptosis and suggests targeting ADAR1/miR-21 signalling as a therapeutic opportunity in sepsis-related lung injury.

Tracking Research on Hemoglobin-Based Oxygen Carriers: A Scientometric Analysis and In-Depth Review.

Numerous studies on the formulation and clinical applications of novel hemoglobin-based oxygen carriers (HBOCs) are reported in the scientific literature. However, there are fewer scientometric analysis related to HBOCs. Here, we illustrate recent studies on HBOCs using both a scientometric analysis approach and a scope review method. We used the former to investigate research on HBOCs from 1991 to 2022, exploring the current hotspots and research trends, and then we comprehensively analyzed the relationship between concepts based on the keyword analysis. The evolution of research fields, knowledge structures, and research topics in which HBOCs located are revealed by scientometric analysis. The elucidation of type, acting mechanism, potential clinical practice, and adverse effects of HBOCs helps to clarify the prospects of this biological agent. Scientometrics analyzed 1034 publications in this research field, and these findings provide a promising roadmap for further study.

Biomarkers for prediction of neurological complications after acute Stanford type A aortic dissection: A systematic review and meta-analysis.

BACKGROUND: The predictive value of biomarkers such as neuron specific enolase (NSE), S100B, neurofilament (NFL), interleukin-6 (IL-6), coagulation factor R, and D-Dimer (DD) after acute Stanford A type aortic dissection (AAAD) with neurological complications has recently gained much attention from the research community. However, results from these studies are conflicting. This meta-analysis is conducted to assess the relationship between the biomarkers and the risk of neurological complications after AAAD. METHODS: Two reviewers performed a systematic literature search across eight databases (CNKI, Wan Fang, VIP, CBM, PubMed, Web of Science, Cochrane Library, and EMBASE). The studies regarding biomarkers in AAAD patients published up to February 2022 were included. These studies were subjected to rigorous scrutiny and data extraction to determine the weighted mean difference (WMD) and the 95% confidence interval (CI), which were analyzed using the RevMan 5.4 and Stata software 14.0. RESULTS: A total of 12 studies including 360 cases with neurological complications and 766 controls were incorporated into our meta-analysis. WMD analysis showed that there was a higher NSE levels in AAAD patients with postoperative neurological complications compared with controls (WMD = 0.640, 95% CI: 0.205 ~ 1.075, P = 0.004 < 0.005), and the level of S100B was related to the 6 h and 24 h postoperative neurological complications (6 h: WMD = 0.64, 95% CI: 0.27 ~ 1.02, P = 0.0007 < 0.001; 24 h: WMD = 0.281, 95% CI: 0.211 ~ 0.351, P < 0.001). Moreover, S100B levels at 6 hours after operation were significantly higher than that at 24 hours (WMD = 0.260, 95% CI: 0.166 ~ 0.354, P < 0.001). CONCLUSION: NSE and S100B are both candidate biomarkers to predict postoperative neurological complications in patients with AAAD. Other markers are also valuable when used in conjunction with clinical judgement. The findings accentuate the necessity of further research to establish standardized values for these biomarkers in predicting neurological complications.

Peripheral immune cell death in sepsis based on bulk RNA and single-cell RNA sequencing.

Background: Immune cell activation in early sepsis is beneficial to clear pathogens, but immune cell exhaustion during the inflammatory response induces immunosuppression in sepsis. Here, we studied the relationship between immune cell survival status and the prognosis of sepsis patients. Methods: Sepsis patients admitted to our hospital with a diagnosis time of less than 24 h were recruited. RNA sequencing technologies were used to study functional alterations in various immune cells in peripheral blood mononuclear cells (PBMCs) from sepsis patients. Flow cytometry and electron microscopy were performed to study cell apoptosis and morphological alterations. Results: A total of 68 sepsis patients with complete data were enrolled and divided into survival (45 patients) and death (23 patients) groups according to their prognosis. Patients in the death group had significantly increased lactic acid levels compared with those in the survival group, but there was no significant difference in other physiological and coagulation functional indicators between the two groups. Bulk RNA sequencing showed that cell death-related pathways and biomarkers were highly enriched and activated in the PBMCs of the death group than that in the survival group. Signs of mitochondrial damage, autophagosomes, cell surface damage and cell surface pore forming were also more pronounced in PBMCs from the death group under electron microscopy. Further single-cell RNA sequencing revealed that cell death occurred mainly in myeloid cells rather than lymphocytes at the early stage of sepsis; cell death patterns of destructive necrosis and pyroptosis were predominant in neutrophils, and apoptosis, autophagy and ferroptosis with less damage to the surroundings were predominant in monocytes. Conclusion: Cell death mainly occurs in monocytes and neutrophils in the PBMCs of sepsis at the early stage. The study provides a perspective for the immunotherapy of early sepsis targeting immune cell death.

D-DI/PLT can be a prognostic indicator for sepsis.

Aims: To investigate the indicators affecting the early outcome of patients with sepsis and to explore its prognostic efficacy for sepsis. Methods: We collected clinical data from 201 patients with sepsis admitted to the emergency department of Xijing Hospital between June 2019 and June 2022. The patients were categorized into groups (survival or fatality) based on their 28-day prognosis. The clinical characteristics, biochemical indexes, organ function-related indicators, and disease scores of the patients were analyzed for both groups. Risk factor analysis was conducted for the indicators with significant differences. Results: Among the indicators with significant differences between the deceased and survival groups, D-dimer (D-DI), Sequential Organ Failure Assessment (SOFA) score, platelet (PLT), international normalized ratio (INR), and D-DI/PLT were identified as independent risk factors affecting the prognosis of sepsis patients. Receiver operating characteristic (ROC) curves showed that D-DI/PLT (area under the curve (AUC) = 93.9), D-DI (AUC = 89.6), PLT (AUC = 81.3), and SOFA (AUC = 78.4) had good judgment efficacy. Further, Kaplan Meier (K-M) survival analysis indicated that the 28-day survival rates of sepsis patients were significantly decreased when they had high levels of D-DI/PLT, D-DI, and SOFA as well as low PLTs. The hazard ratio (HR) of D-DI/PLT between the two groups was the largest (HR = 16.19). Conclusions: D-DI/PLT may be an independent risk factor for poor prognosis in sepsis as well as a clinical predictor of patient prognosis.

Alteration of gut microbiota after heat acclimation may reduce organ damage by regulating immune factors during heat stress.

Introduction: Heat-related illnesses can lead to morbidity, which are anticipated to increase frequency with predictions of increased global surface temperatures and extreme weather events. Although heat acclimation training (HAT) could prevent heat-related diseases, the mechanisms underlying HAT-promoting beneficial changes in organ function, immunity, and gut microbes remain unclear. Methods: In the current study, we recruited 32 healthy young soldiers and randomly divided them into 4 teams to conduct HATs for 10 days: the equipment-assisted training team at high temperature (HE); the equipment-assisted training team under normal hot weather (NE); the high-intensity interval training team at high temperature (HIIT), and the control team without training. A standard heat tolerance test (HTT) was conducted before (HTT-1st) and after (HTT-2nd) the training to judge whether the participants met the heat acclimation (HA) criteria. Results: We found that the participants in both HE and NE teams had significantly higher acclimation rates (HA/total population) than whom in the HIIT team. The effects of HAT on the participants of the HE team outperformed that of the NE team. In the HA group, the differences of physiological indicators and plasma organ damage biomarkers (ALT, ALP, creatinine, LDH, α-HBDH and cholinesterase) before and after HTT-2nd were significantly reduced to those during HTT-1st, but the differences of immune factors (IL-10, IL-6, CXCL2, CCL4, CCL5, and CCL11) elevated. The composition, metabolism, and pathogenicity of gut microbes changed significantly, with a decreased proportion of potentially pathogenic bacteria (Escherichia-Shigella and Lactococcus) and increased probiotics (Dorea, Blautia, and Lactobacillus) in the HA group. Training for a longer time in a high temperature and humidity showed beneficial effects for intestinal probiotics. Conclusion: These findings revealed that pathogenic gut bacteria decrease while probiotics increase following HA, with elevated immune factors and reduced organ damage during heat stress, thereby improving the body's heat adaption.

[Correlation analysis of clinical indicators and liver failure-related prognostic score associated with prognosis in patients with amanita phalloides poisoning].

OBJECTIVE: To analyze and compare the clinical indicators and the liver failure-related prognostic score of patients with amanita phalloides poisoning with different prognoses, and to explore potential prognostic indicators. METHODS: A retrospective case-control study was conducted. The clinical data of 52 patients with amanita phalloides poisoning admitted to the department of emergency of Xijing Hospital Affiliated to Air Force Medical University from September 2016 to September 2021 were collected, including general information (gender, age), clinical indicators at admission [mean arterial pressure (MAP), total bilirubin (TBil), aspartate transaminase (AST), alanine transaminase (ALT), albumin (ALB), serum creatinine (SCr), blood urea nitrogen (BUN), creatine kinase (CK), D-dimer, fibrinogen degradation product (FDP), prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin activity (PTA), international normalized ratio (INR), white blood cell count (WBC), platelet count (PLT)], liver failure-related prognostic score [sequential organ failure assessment (SOFA), chronic liver failure (CLIF)-SOFA score, European Foundation for the Study of Chronic Liver Failure-organ failure (CLIF-C OF)], and 28-day outcome. The clinical indicators and liver failure-related prognostic scores of the patients with different prognoses were compared. Receiver operator characteristic curve (ROC curve) was used to determine the prognostic value of statistically significant indicators between different prognosis of patients with amanita poisoning. RESULTS: A total of 45 patients were enrolled, of which 38 survived and 7 died within 28 days. The coagulation indicators including PT, APTT, INR, and liver failure-related prognostic scores including SOFA score, CLIF-SOFA score, and CLIF-C OF score in the patients of death group were significantly higher than those in the survival group [PT (s): 69.59±15.94 vs. 25.99±4.64, APTT (s): 83.44±17.82 vs. 42.64±3.79, INR: 6.13±1.47 vs. 2.07±0.33, SOFA score: 11.57±1.38 vs. 6.03±0.77, CLIF-SOFA score: 9.86±2.17 vs. 5.55±0.67, CLIF-C OF score: 11.71±0.97 vs. 8.37±0.35], and PLT was significantly lowered (×109/L: 80.57±29.65 vs. 169.60±11.80, all P < 0.05). ROC curves showed that coagulation indicators including PT, APTT, INR, PLT, and liver failure-related prognostic scores including SOFA score and CLIF-C OF score were associated with the prognosis of patients with amanita phalloides poisoning, with the area under the ROC curve (AUC) of > 0.75. The sensitivity of the clinical indicators was above 85%, and the AUC and specificity of INR were the highest, which were 0.88 [95% confidence interval (95%CI) was 0.74-1.00] and 83.0%, respectively; meanwhile, the sensitivity of the liver failure-related prognostic scores was 100%, and the AUC and specificity of the CLIF-C OF score were the highest, which were 0.86 (95%CI was 0.74-0.99) and 66.0%, respectively. CONCLUSIONS: INR and CLIF-C OF score can be used to evaluate the poor prognosis of patients with amanita phalloides poisoning.