Heatstroke is a fatal disease caused by heat injury. With global warming, the incidence of heatstroke has been increasing year by year. Combined coagulation dysfunction is an important factor in the mortality of heatstroke. So far, there is no standard for the diagnosis and treatment of heatstroke-induced coagulopathy at home and abroad. Therefore, Expert Group of Heatstroke Prevention and Treatment of Chinese People's Liberation Army; People's Liberation Army Professional Committee of Critical Care Medicine; Chinese Society of Thrombosis, Hemostasis and Critical Care, Chinese Medicine Education Association; Chinese Society of Thrombosis and Hemostasis, Chinese Research Hospital Association jointly organized experts to develop a expert consensus on the diagnosis and treatment of heatstroke-induced coagulopathy in China. This consensus includes five parts: the definition, pathogenesis, diagnosis and evaluation, treatment and control of complications of heatstroke-induced coagulopathy, with a total of 15 recommended opinions to guide clinical work.

Objective To explore the association between triglyceride glucose (TyG) index and TyG-body mass index (TyG-BMI) and the prevalence of metabolic associated fatty liver disease (MAFLD) in the elderly men. Methods Totally 2290 elderly men were selected from January to December in 2021 in the Second Medical Center of Chinese PLA General Hospital, and divided into MAFLD group (n=1322) and non-MAFLD group (n=968). Multivariate logistic regression was used to analyze the association between TyG index, TyG-BMI and MAFLD. The receiver operating characteristic (ROC) curve was drawn to explore the predictive value of TyG index and TyG-BMI with MAFLD in the elderly men. Results Two thousand two hundred and ninety elderly men were (74.3±10.1) years old, and an average BMI of (24.63±2.70) kg/m². BMI, γ‑glutamyl transaminase (γ‑GT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (Scr), thyroid stimulating hormone (TSH), free triiodothyronine (FT₃), the rate of smoking and drinking, and the prevalence of hypertension, diabetes, hyperuricemia, high triglyceride (TG), low high density lipoprotein cholesterol (HDL-C), hyperuricemia, thyroid nodules and cholelithiasis were all significantly higher in non-MAFLD group than those in MAFLD group (P<0.05), while the age of MAFLD group was lower than that of non-MAFLD group (P=0.003). Multivariate logistic regression analysis showed that the risk of MAFLD in patients of TyG quartile groups Q₂, Q₃, Q₄ was 1.667 (95%CI 1.257-2.236, P<0.001), 2.004 (95%CI 1.482-2.710, P<0.001) and 5.420 (95%CI 3.266-8.995, P<0.001) times higher than that of TyG Q₁, respectively. The risk of MAFLD in patients of TyG-BMI Q₂, Q₃, Q₄ was 2.215 (95%CI 1.549-3.167, P<0.001), 2.809 (95%CI 1.723-4.580, P<0.001) and 2.513 (95%CI 1.253-5.040, P=0.009) times higher than that of TyG-BMI Q₁, respectively. The ROC curve showed that areas under the curve (AUC) of MAFLD predicted by TyG index and TyG-BMI were 0.717 (95%CI 0.696-0.738) and 0.840 (95%CI 0.823-0.856), and the best cut-off values were 8.63 and 205.20, respectively. Moreover, the ROC curve showed that AUC of MAFLD in the elderly men without hyperlipidemia or diabetes predicted by TyG index and TyG-BMI were 0.653 (95%CI 0.622-0.684) and 0.840 (95%CI 0.818-0.862), and the best cut-off values were 8.42 and 202.66, respectively. In addition, AUC, accuracy, specificity, sensitivity, positive predictive value and negative predictive value predicted by TyG-BMI were higher than those by TyG index. Conclusions TyG index and TyG-BMI are significantly associated with MAFLD in the elderly men. Both TyG index and TyG-BMI have certain predictive value for the prevalence of MAFLD in the elderly men, and TyG-BMI may be better.

Objective To explore the change of brain functional connectivity strength in patients with type 2 diabetes mellitus (T2DM) and its neuropathological mechanism. Methods Fifty-six T2DM patients who visited Gansu Provincial Hospital from October 2017 to March 2021 were selected as T2DM group, and 48 healthy controls were selected as control group. A prospective study was conducted on the changes in brain function in T2DM patients by analysis of resting state functional connectivity strength (FCS) and functional connectivity (FC) based on seed points. Brain functional magnetic resonance imaging, clinical variable collection, and neuropsychological testing of patients in two groups were performed. We calculate the FCS value, evaluate the brain function changes of the two groups in the resting state, take the brain regions with significant differences between the groups as the seed points and perform functional connectivity analysis with the whole brain. Correlation analysis was conducted between the FCS, FC values of the different brain regions and clinical variables such as fasting blood glucose (FPG), glycosylated hemoglobin (HbA_1c), thyroid hormone (TSH) levels, as well as the scores of mini mental state examination (MMSE), Montreal cognitive assessment (MoCA), clock drawing test (CDT), Hamilton Depression Rating Scale (HAMD-24) and Hamilton Anxiety Scale (HAMA). Results Compared with control group, the HAMD-24 and HAMA scores in T2DM group significantly increased (P<0.01), while the MoCA scores decreased (P<0.05); In T2DM group, the FCS value of the right middle temporal gyrus increased (GRF correction, voxel level P<0.001, clustering level P<0.05), and the FC value of the right middle temporal gyrus-left anterior cingulate cortex decreased (GRF correction, voxel level P<0.001, clustering level P<0.05). Correlation analysis showed that the FC value of right middle temporal gyrus-left anterior cingulate cortex in T2DM patients was negatively correlated with HAMD-24 score (r=-0.395, P=0.003), HbA_1c level (r=-0.303, P=0.023), and positively correlated with TSH level (r=0.324, P=0.017). Conclusions The increase of FCS value in the right middle temporal gyrus and the decrease of FC value in the right middle temporal gyrus-left anterior cingulate cortex may be important neuroimaging features of brain function damage in T2DM patients. HbA_1c may play an important role in the process of brain damage in T2DM patients.

Objective To investigate the release of enterogenic and hepatogenic high mobility group protein B1 (HMGB1) through exosomes and its regulatory pathway. Methods We used wild-type (WT) and ASC^-/- mice for this study. We randomly selected five mice per group from each strain and fed them either a normal diet (ND) or a high-fat diet (HFD) for eight weeks. The control group consisted of WT mice fed with the normal diet; the HFD group were WT mice with the HFD; the microflora disturbance (MD) group were ASC^-/- mice fed with the normal diet; the high-lipid microflora disturbance (HLMD) group were ASC^-/- mice with HFD. We used confocal microscopy to detect the co-localization of liver and intestinal exosome markers with HMGB1. We then measured the expression level of HMGB1 content in exosomes by Western blotting and PCR. The AML12 cells were treated with palmitic acid (PA) and lipopolysaccharide (LPS) for 24 h to build an in vitro model. We also detected HMGB1/CD63 levels using Western blotting. To understand the regulatory mechanism of exosome release, we employed siRNA intervention. Results The secretion of exosomes increased significantly in HFD group compared with control group [(3.5±0.2) ng/ml vs. (1.1±0.3) ng/ml, P<0.05], HLMD group compared with those in MD group [(3.2±0.2) ng/ml vs. (1.9±0.4) ng/ml, P<0.05]. Using immunofluorescence detection, we observed increased co-localization of exosome markers (ALP or VPS16) with HMGB1 in HFD group compared with control group. We also observed this in AML12 cells treated with PA and LPS compared with blank control. The PCR data showed that HMGB1 in hepatocyte exosomes was higher in HFD group compared with control group (41.5±10.2 vs. 1.3±0.3, P<0.05), HLMD group was significantly higher than that in MD group (48.6±7.2 vs. 1.5±0.5, P<0.05). TLR4 expression was higher in HFD group compared with control group (13.8±6.2 vs. 2.8±0.9, P<0.05), HLMD group compared with MD group (22.6±4.1 vs. 2.5±1.5, P<0.05). In intestinal mucosal cells, the co-location of HMGB1 and exosome marker CD63 was significantly higher in HFD group compared with control group (0.6±0.2 vs. 0.4±0.1, P<0.05), and HLMD group compared with MD group (0.9±0.2 vs. 0.5±0.1, P<0.05). In vitro, the HMGB1 of exosomes was increased in endotoxin group (5.1±0.8) and high lipid endotoxin group (5.5±0.7) compared with control group (3.8±0.6, P<0.05). On the other hand, the HMGB1 of exosomes in the cell siRNA intervention group was not increased compared with control group (3.7±0.6 vs. 3.8±0.6, P>0.05). Conclusion HMGB1 is released by exosomes in hepatocytes and intestinal cells, and regulated by Toll-like receptor 4 (TLR4) under a high-fat diet and intestinal flora disorder, which may be one of the contributing factors in promoting the development of steatohepatitis.

Objective To investigate the effects and mechnism of abnormal stress promoting macrophage mobility inhibitory factor (MIF), cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) in the progression of temporomandibular joint osteoarthritis (TMJOA). Methods From January 2020 to December 2021, TMJOA and temporomandibular joint internal derangement (TMJID) patients (30 cases in each group, we divided the TMJOA into group TMJ Ⅰ, Ⅱ, Ⅲ according to the stage) who were admitted to TMJOA special clinic of the First Affiliated Hospital of Xinjiang Medical University and accompanied by abnormal occlusion were collected. The pain score of the occlusal state of the patients was evaluated by visual analogue scale. The expression levels of MIF, COX2 and PGE2 in synovial fluid were detected by ELISA. We used the unilateral anterior crossbite for TMJOA (UAC) rats model (the grouped into: UAC-4 weeks, UAC-8 weeks and UAC-12 weeks group), and control group at the same time (grouped into: Ctrl-4 weeks, Ctrl-8 weeks and Ctrl-12 weeks group), each group had 6 rats. The expression levels of MIF, COX2 and PGE2 in serum and synovial fluid of rats were detected by ELISA. The expression levels of IL-1β, IL-18, MIF, COX2 and PTGER2 in temporomandibular joint of rats were detected by Western blotting. The fluid flow shear stress (FFSS) model of fibroblast-like synovial cells (FLSs) was established, and the mRNA and protein expression levels of above indexes were detected by RT-PCR and Western blotting. Results Visual analogue scale evaluation showed that the pain score of TMJOA Ⅰ and Ⅱ group was significantly higher than that of TMJID (P<0.001). ELISA results showed that the expression levels of MIF, COX2 and PGE2 in synovial fluid in TMJOA group were higher than those in TMJID group (P<0.05), and the expression levels were the highest in TMJOA Ⅱ group. Compared with control group, the expressions of MIF, COX2 and PGE2 in serum and synovial fluid at UAC-4 weeks, 8 weeks and 12 weeks were slightly higher, and significantly higher at UAC-8 weeks in rat TMJOA model (P<0.05). In addition, the expression trend of protein levels in temporomandibular joint tissues was similar, which showed higher expression levels of IL-1β, IL-18, MIF, COX2 and PTGER2 (P<0.05). In the cell model where FFSS interfered with FLSs, with the increase of FFSS, cell with deformation, incomplete cell membrane and reduced number. Compared with control group, the expression levels of IL-1β, IL-18, MIF, COX2 and PGE2 (PTGER2) of FLSs were increased in 1, 3, 5 and 10 dyn/cm² intervention groups (P<0.05). Conclusion MIF, COX2 and PGE2 were highly expressed in temporomandibular joint synovial fluid of TMJOA patients with malocclusion. And these three factors were also highly expressed in serum and synovial fluid of UAC rats. The abnormal fluid shear stress promotes the secretion of MIF, COX2 and PGE2 by FLSs to participate in joint microenvironment inflammation and accelerate disease progression.

Objective To study the expression profile and possible roles of ferroptosis-related genes in a bleomycin-induced murine model of pulmonary fibrosis. Methods Twelve 6-7-week-old male C57BL/6 mice were randomly divided into model group and control group, 6 in each group. The model group received nasal inhalation of bleomycin, while the control group was given an equal volume of normal saline. Lung tissues were collected 3 weeks after modeling. Pathological changes and collagen deposition in lungs were observed by HE and Masson staining. Prussian blue staining was used to observe the level of iron accumulation in lung tissue. Total RNA was extracted for PCR Array to identify ferroptosis-related differentially expressed genes (DEGs). Functional analysis for DEGs was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Expression levels of DEGs were verified by RT-qPCR analysis. Results Compared with control group, fibrosis and obvious iron deposition occured in mouse lung tissue of model group. The PCR array identified five ferroptosis-related genes that expression significantly decreased in model group compared with control group including carbonic anhydrase 9 (CA9), cysteinyl-tRNA synthetase 1 (CARS1), heat shock transcription factor 1 (HSF1), NADPH oxidase 3 (NOX3) and mitochondrial ferritin (FTMT)(P<0.05). GO functional enrichment analysis and KEGG pathway analysis showed that the DEGs were mainly related to temperature homeostasis, NADPH oxidase complex, and carbonate dehydratase activity, and were involved in nitrogen metabolism, aminoacyl-tRNA biosynthesis and legionellosis signaling pathways. RT-qPCR verification confirmed that the expression levels of CA9, CARS1, HSF1 and FTMT were significantly decreased in model group than those in control group (P<0.05). Conclusions Change of the expression of genes related to ferroptosis has been confirmed in a murine model of pulmonary fibrosis induced by bleomycin. The result indicates that ferroptosis is involved in the process of idiopathic pulmonary fibrosis, ferroptosis-associated DEGs might provide potential targets for clinical treatment of it.

Objective To explore the efficacy of contrast-enhanced ultrasound (CEUS) combined with mixed reality (MR) in laparoscopic anatomical hepatectomy. Methods The clinical data of 45 patients with primary liver cancer who underwent laparoscopic anatomical hepatectomy in Luoyang Central Hospital Affiliated to Zhengzhou University from January 2019 to June 2022 were retrospectively analyzed. All patients underwent abdominal thin-layer enhanced CT scan before operation, then collected data to build a three-dimensional visualization model of the liver. According to the auxiliary method of intraoperative imaging, the patients were divided into observation group (n=25, CEUS combined with MR technology was used to provide precise navigation for surgery) and the control group (n=20, routine anatomical hepatectomy was performed, and CEUS and MR technology were not used during surgery). The postoperative follow-up was to January 2023. The size of the lesion, the time of operation, the time of selective hepatic blood flow blockade, the amount of intraoperative bleeding, the intraoperative and postoperative complications, the rate of R0 resection, the length of hospital stay, the postoperative liver function [alanine aminotransferase (ALT), aspartate aminotransferase(AST), creatinine level], and the survival time were recorded and compared between two groups. Results The remaining 42 patients were successfully operated under laparoscopy except for 3 patients in control group who were converted to laparotomy. There was no statistically significant difference in lesion size between the two groups [(5.6±1.1) cm vs. (5.4±1.3) cm, P>0.05]. The observation group had significantly shorter intraoperative selective hepatic blood flow blockade time and surgical time compared to control group [(27.1±6.8) min vs. (46.9±4.3) min, P<0.001; (135.4±4.3) min vs. (199.3±5.8) min, P<0.001]. The intraoperative blood loss and transfusion volume of observation group were significantly lower than those in control group [(102.7±10.1) ml vs. (259.4±16.9) ml, P<0.001; (120.7±9.6) ml vs. (247.4±12.3) ml, P<0.001], the levels of ALT and AST were significantly lower than those in control group 24 h after operation [(96.7±23.7) U/L vs. (185.3±38.5) U/L, P<0.001; (91.4±30.9) U/L vs. (198.1±42.6) U/L, P<0.001]. One patient in the observation group developed postoperative pulmonary infection (1/25, 4.0%), and recovered after conservative treatment. In the control group, 3 patients (3/20, 15.0%) underwent massive intraoperative hemorrhage, resulting in conversion to laparotomy, 2 patients (2/20, 10.0%) experienced postoperative pulmonary infection, and 2 patients (2/20, 10.0%) experienced gastric emptying dysfunction, all patients recovered after conservative treatment. Neither patient in the two groups experienced abdominal bleeding, biliary fistula and other complications after operation. The incidence of complications in the observation group was lower than that in control group, and the difference was statistically significant (P=0.021). There was no statistically significant difference in postoperative creatinine levels, R0 resection rate, and postoperative hospital stay between the two groups [(57.4±18.2) μmol/L vs. (58.1±17.6) μmol/L, P>0.05; 100.0%(25/25) vs. 90.0%(18/20), P>0.05; (8.4±2.2) d vs. (8.9±1.9) d, P>0.05]; The median survival time of observation group was longer than that of control group, but the difference was not statistically significant [18.5(9.2, 24.5) months vs. 18.0 (8.7, 23.0) months, P>0.05]. Conclusion The combination of CEUS and MR technology is safe and effective in laparoscopic anatomical hepatectomy, which can shorten the operation time, reduce intraoperative bleeding, completely remove the tumor, and improve the treatment effect, and has good clinical application value.

Objective To investigate the effect and its mechanism of vitamin A (VA) deficiency (VAD) on regulating alveolar macrophage polarization in neonatal rats with acute respiratory distress syndrome (ARDS). Methods Sixty neonatal SD rats were divided into vitamin A normal control group (VAN ctrl group, n=10), normal vitamin A group (VAN group, n=10), vitamin A deficiency control group (VAD ctrl group, n=10), vitamin A deficiency group (VAD group, n=10), vitamin A rescue control group (VADR ctrl group, n=10) and vitamin A rescue group (VADR group, n=10). The VADR ctrl and VADR groups were injected with 25 µg VA at the second day after birth. All the neonatal rats were given lipopolysaccharide (LPS) to establish the neonatal rat model of ARDS, and serum and lung tissue samples were collected. The weight of newborn rats in each group was recorded before modeling, the May-Grunwald-Giemsa staining was performed to observe the number of main cells in bronchoalveolar lavage fluid (BALF), and HE staining was used to detect the pathological damage of lung tissue. The polarization of alveolar macrophages was evaluated by immunofluorescence. qRT-PCR and ELISA were performed to detected the expression of downstream markers of the polarization of alveolar macrophages inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10 and arginase-1 (Arg-1). The content of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were calculated by colorimetric method, and cell apoptosis was detected by TUNEL. Results Compared with the neonatal rats in VAN group, the neonatal rats in VAD group had lower body weight, small physique, and sparse hair, while the body weight and general condition of the newborn rats in the VADR group did not change significantly. Compared with the VAD group, the neonatal rats in VADR group gained weight and shiny hair. Compared with VAN group, the lung damage of ARDS neonatal rats in VAD group was aggravated, the number of major cells in BALF increased, the M1 polarization of alveolar macrophages activated (P<0.05), the expression levels of M1 polarization markers iNOS, IL-6, TNF-α and CD86 increased significantly (P<0.05), the content of oxidative stress marker MDA and cell apoptosis increased (P<0.05), SOD activity decreased (P<0.05), while the levels of IL-10 and Arg-1 were not statistically significant (P>0.05); Compared with VAN group, there were no significant differences in macrophage M1 polarization, TNF-α, IL-6, SOD, MDA, IL-10 and Arg-1 in newborn rats in VADR group (P>0.05). Compared with VAD group, the lung damage of ARDS neonatal rats in VADR group was significantly reduced, the number of alveolar macrophages and the polarization of alveolar macrophages M1 decreased (P<0.05), the expression levels of M1 polarization markers iNOS, IL-6, TNF-α and CD86 decreased (P<0.05), the content of the oxidative stress marker MDA and cell apoptosis decreased (P<0.05), and the SOD activity enhanced (P<0.05). Conclusion VAD could regulate the M1 polarization of alveolar macrophages, up-regulated the expression of inflammatory markers downstream of M1 polarization, increased pulmonary oxidative stress and apoptosis, and aggravated ARDS in neonatal rats.

Objective To report a case of symmetric peripheral gangrene (SPG) in septic shock. The clinical data and related literature were reviewed to discuss its characteristics, pathogenesis and treatment measures, so as to improve clinicians' understanding and treatment of the disease. Methods A 60-year-old male patient was admitted to the Changhai Hospital Affiliated to Naval Medical University on July 31, 2022 due to "left side low back pain". Before operation, he was diagnosed with malignant tumor of the left adrenal gland involving multiple organs and blood vessels. Therefore, he underwent resection of huge retroperitoneal tumor, left colon, left kidney, left suprarenal gland, part of stomach and pancreatic body tail under general anesthesia. Due to the large surgical trauma, more bleeding and low blood pressure, he was admitted to the ICU for blood transfusion, fluid infusion and pressure boosting. The literature about SPG in the past 10 years in the database of the National Library of Medicine (PubMed) was searched, and the characteristics of the disease, the related factors of the disease and the treatment measures were emphatically discussed. Results The patient developed septic shock due to intraperitoneal infection on the 3rd day after operation, and gradually developed symmetrical ischemic necrosis of both hands and feet on the 4th day. According to the characteristics of the disease and clinical features, the patient was diagnosed with SPG. A total of 18 foreign English literatures were retrieved, involving 24 SPG patients. In combination with this case, 25 patients were included, including 10 males (40%) and 15 females (60%). The male to female ratio was 1:1.5. The average age was (48.8±15.1) years for males and (49.8±16.2) years for females. There was no history of vascular related diseases in the past. The main clinical features were symmetrical ischemic necrosis of both hands and (or) lower limbs and feet (100%), which was related to septic shock (100%), microbial infection (52%), disseminated intravascular coagulation (DIC) (52%), liver function damage (20%), and the use of vasoactive drugs (80%). The treatment effect was poor, the death mortality was 24% (6/25), and the amputation rate of the surviving patients was as high as 78.9% (15/19). Only one case of blood adsorption treatment was effective. Conclusions The occurrence of SPG in septic shock patients may be related to the pathophysiological changes such as septic shock, DIC, lack of natural anticoagulants, and the role of vasoactive drugs. Clinicians need to pay great attention to improving the diagnosis and treatment of SPG.

Objective To evaluate the clinical value to characterize abdominal lymphadenopathy in autoimmune liver diseases (AILD) patients using computed tomography (CT). Methods We recruited 136 AILD patients (set as AILD group) from January 2015 to December 2019 and 65 patients with other liver diseases (set as control group). We assessed the volume and number of the enlarged lymph nodes in different lymph centers using CT. To evaluate the diagnosis value of abdominal lymphadenopathy for AILD, we calculated the area under the receiver operating characteristic curve (AUROC) of abdominal lymphadenopathy. We further employed logistic regression to analyze the risk factors associated with perihepatic lymph node enlargement. Results The abdominal lymph nodes in AILD group had significantly increased average volume and number than those in control group [(0.47±0.61) cm³ vs. (0.25±0.20) cm³;8.10±4.97 vs. 4.26±3.25, P<0.001]. The combination of the number of hepatic lymph nodes and the volume of mesenteric lymph nodes showed well diagnostic value for AILD (AUROC=0.816, P<0.001). Within 77 AILD patients, who underwent liver biopsy, patients with positive hepatic lymphadenopathy showed a significantly higher proportion of interface hepatitis in liver tissues than patients with negative hepatic lymphadenopathy (52.31% vs. 16.67%, χ²=5.169, P<0.05). Multivariate analysis showed that the serum IgG level is a risk factor for perihepatic lymph node enlargement (OR=1.012, 95%CI 1.000-1.024, P<0.05). Conclusions The enlargement of hepatic and mesenteric lymph nodes is of value in the differential diagnosis of AILD. Enlargement of hepatic lymph nodes is correlated with the disease activity in AILD.