Objective To investigate the effect of dapagliflozin on cardiac function and major adverse cardiac events (MACE) in elderly patients with heart failure after acute myocardial infarction. Methods The clinical data of 59 elderly patients with heart failure after acute myocardial infarction, treated in Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology from May 2021 to February 2022, were collected and retrospectively analyzed. The objects were divided into control group (n=29) and dapagliflozin group (n=30) according to whether they took dapagliflozin during routine treatment. The cardiac function indexes [left vetricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter(LVESD)] and the level of N-terminal pro-brain natriuretic peptide (NT-proBNP); as well as clinical total effective rate, Killip grading and MACE occurrence were detected and compared at discharge and within 6 months after discharge. Results At discharge and within 6 months' treatment, the levels of LVEF increased (P<0.05), and of LVEDD, LVESD and NT-proBNP decreased (P<0.05) in the two groups than those before treatment. The level of LVEF in the dapagliflozin group was higher (P<0.05), and the levels of LVEDD, LVESD and NT-proBNP were lower in dapagliflozin group (P<0.05) than those in control group. There was no statistical difference in the clinical total effective rate between the two groups (86.7% vs. 65.5%, P>0.05) at discharge; The clinical total effective rate of dapagliflozin group was 93.3%, which was higher than control group of 62.1% within 6 months' treatment (P<0.05). Before treatment, at discharge and within 6 months' treatment, there was no statistical difference in the Killip classification between the two groups (P≥0.05). The incidence of MACE in dapagliflozin group was lower than that in control group within 6 months' treatment (P<0.05). Conclusion Compared with conventional anti heart failure therapy, combined with dapagliflozin can improve the cardiac function and prognosis, reduce the incidence of MACE of patients with heart failure after acute myocardial infarction.

Objective To investigate the effects and mechanisms of TAR DNA-binding protein 43 (TDP-43) on oxygen-glucose deprivation (OGD)-induced apoptosis in mouse atrial myocytes (HL-1 cells). Methods The in vitro cultured mouse atrial myocytes (HL-1 cells) were divided into: (1) control group and groups with different OGD treatment times (2, 4, 8, 16 h), and cell viability was detected by CCK-8 assay, and TDP-43 protein expression level was detected by Western blotting, which was used to determine the time point of OGD induction for the subsequent study; (2) control and OGD groups, flow cytometry was used to detect apoptosis, JC-1 staining to detect mitochondrial membrane potential, chemiluminescence to detect adenosine triphosphate (ATP) relative content, microplate method to detect malondialdehyde (MDA) content, and WST-1 method to detect superoxide dismutase (SOD) content. Mouse atrial myocytes (HL-1 cells) transfected with lentivirus were divided into: (1) negative control lentiviral intervention group (NC-shRNA), TDP-43 knockdown lentiviral intervention group (TDP-43-shRNA1, TDP-43-shRNA2, TDP-43-shRNA3), and Western blotting was used to detect the TDP-43 protein expression level, and the group with the highest lentiviral knockdown efficiency was selected as the TDP-43-shRNA for subsequent experiments; (2) NC-shRNA group, TDP-43-shRNA group, OGD+NC-shRNA group, OGD+TDP-43-shRNA group, under normoxic and OGD conditions, flow cytometry was used to detect the apoptosis rate, MitoTracker staining to detect mitochondrial morphology, JC-1 staining to detect mitochondrial membrane potential, chemiluminescence to detect the relative content of ATP, flow cytometry to detect the fluorescence intensity of reactive oxygen species (ROS), microplate to detect the content of MDA, and WST-1 to detect the content of SOD. Results CCK-8 method showed that, with the prolongation of OGD time, the viability of mouse atrial myocytes (HL-1 cells) gradually decreased; Western blotting assay showed that the expression level of TDP-43 protein gradually increased, and both of them showed a strong time-dependence. Compared with control group, mouse atrial myocytes (HL-1 cells) viability was the lowest (P<0.05) and TDP-43 protein expression was the highest (P<0.05) at 16 h of OGD, accordingly, OGD 16 h was chosen as the induction time point for subsequent experiments. Compared with control group, the apoptosis rate, the fluorescence intensity ratio of mitochondrial membrane potential and the content of MDA increased, the relative content of ATP and SOD decreased in OGD group, and the differences were all statistically significant (P<0.05). Western blotting detection showed that compared with NC-shRNA group, the TDP-43-shRNA2 group had the most obvious reduction in TDP-43 protein expression level (P<0.05) and the highest knockdown efficiency, so the TDP-43-shRNA2 group was selected for subsequent experiments. The results of flow cytometry showed that under normoxic conditions, there was no significant change in the apoptosis rate in TDP-43-shRNA group compared with NC-shRNA group (P>0.05); and under OGD conditions, the apoptosis rate in OGD+TDP-43-shRNA group reduced when compared with OGD+NC-shRNA group (P<0.05). MitoTracker staining results showed that the mitochondrial morphology of TDP-43-shRNA group was intact without significant changes compared with NC-shRNA group; the mitochondria of OGD+NC-shRNA group increased in number, most of which were fragmented and scattered in distribution; compared with OGD+NC-shRNA group, the mitochondrial morphology of OGD+TDP-43-shRNA group was restored. Under normoxic conditions, there were no significant changes in mitochondrial membrane potential, relative ATP content, ROS fluorescence intensity, MDA content, and SOD content in TDP-43-shRNA group compared with NC-shRNA group (P>0.05); however, under OGD conditions, the ratio of fluorescence intensity of mitochondrial membrane potential of cells the fluorescence intensity of ROS, and the content of MDA decreased, and the relative content of ATP and the content of SOD increased in OGD+TDP-43-shRNA group compared with that of OGD+NC-shRNA group, and all of these differences was statistically significant (P<0.05). Conclusion TDP-43 exacerbates OGD-induced mitochondrial dysfunction by regulating cardiomyocyte apoptosis; therefore, knockdown of TDP-43 expression is expected to be a potential therapeutic strategy for ischemic cardiomyopathy.

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 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 evaluate the efficacy and safety of modified decompressive craniectomy in treatment of traumatic brain injury and its impact on the serum levels of inflammatory mediators and prognosis. Methods According to different surgical methods, 82 patients with traumatic brain injury admitted to the department of neurosurgery of Nanyang Central Hospital from June 2020 to January 2022 were divided into standard group (n=41) and modified group (n=41). The standard group was given standard decompressive craniectomy, and the modified group was given modified decompressive craniectomy. The intraoperative blood loss, operation time and hospital stay, the levels of neuron-specific enolase (NSE), S-100 calcium binding protein B (S-100β), C-reaction protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) before operation, 6 hours after operation, and 3 days after operation, Glasgow Outcome Scale (GOS), incidence of complications, and incision healing grade 1 month after operation were compared between two groups. Results Compared with standard group, the hospital stay was significant shorter in modified group (P<0.05), and intraoperative blood loss and operation time were no significant difference in modified group (P>0.05). At 6 hours and 3 days after operation, the levels of NSE, S-100β, CRP, PCT and IL-6 in modified group were lower than those in standard group (P<0.05). Compared with standard group, the good prognosis rate based of GOS was higher in modified group [82.9% (34/41) vs. 63.4% (26/41), P<0.05]; the total incidence of complications was lower in modified group [2.4%(1/41) vs. 19.5%(26/41), P<0.05]; and the grade of incision healing was better in modified group (P<0.05). Conclusions Modified decompressive craniectomy in the treatment of traumatic brain injury could reduce stress of brain injury and surgical trauma, and the incidence of complications, help to speed up the postoperative recovery process, improve the rate of good prognosis and the grade of incision healing. Its efficacy and safety is better than standard decompressive craniectomy.

Objective To explore the risk factors for renal injury in tumors patients treated with programmed death receptor-1 (PD-1) inhibitor, and further construct a column chart model to predict the likelihood of renal injury in patients. Methods The present study is a single center retrospective analysis. 447 patients with tumors treated with PD-1 inhibitors in the Third Affiliated Hospital of Soochow University between January 2018 and January 2021 were included and followed up until January 2022. Kidney injury was defined as acute kidney disease (AKD). All patients were divided into AKD group (n=71) and non-AKD group (n=376 according to whether PD-1 inhibitor associated with AKD development at the end of follow-up. Basic information, disease and medication situation, laboratory indicators, and the incidence of extrarenal immune related adverse events (irAEs) during follow-up period were compared between the two groups. Univariate and multivariate logistic regression models were used to identify independent risk factors for PD-1 inhibitor associated AKD. The present study randomly divided all samples (n=447) into training set (n=313) and validation set (n=134) in a 7:3 ratio, built nomogram prediction models in the training set according to the screened independent risk factors, drawn the receiver operating characteristic (ROC) curves to evaluate the discrimination of the models, drawn calibration curves to evaluate the calibration of the models, and drawn clinical decision curve analysis (DCA) to explore the clinical validity and benefit rate of the models. Results The combination of antibiotics, diabetes, hypertension, extrarenal irAEs and cystatin C (Cys C) in AKD group were significantly higher than those in non-AKD group (P<0.05), but hemoglobin (Hb) was significantly lower than that in non-AKD group (P<0.05). Single factor logistic regression analysis showed that combination of antibiotics, diabetes, hypertension, extrarenal irAEs, lower Hb, estimated glomerular filtration rate (eGFR), higher blood urea nitrogen (BUN), serum creatinine (SCr), Cys C, fasting blood glucose (FBG), and alanine transaminase (ALT) were risk factors for PD-1 inhibitor related AKD (P<0.05). Multivariate logistic regression analysis showed that concomitant extrarenal irAEs, lower Hb, higher SCr, and direct bilirubin (DBIL) were independent risk factors for PD-1 inhibitor associated AKD (P<0.05). Based on the independent risk factors mentioned above, a column chart prediction model was further established and validated. The results showed that the area under the ROC curve (AUC) of the training and validation sets of the model were 0.703 (95%CI 0.628-0.777) and 0.791 (95%CI 0.671-0.911), respectively, indicating good discrimination. The calibration curves of both the training and validation sets hover around the ideal line of 45°, indicating that the model has good calibration. DCA shows that the constructed model curve is far away from the two polar lines (the curve with a net benefit of 0 and the curve with all samples being positive), indicating that the model has good clinical benefits. Conclusion The combination of extrarenal irAEs, lower Hb, higher SCr, and higher DBIL are independent risk factors for the occurrence of PD-1 inhibitor related AKD; The established column chart model has good discrimination and calibration, which can provide guidance for clinical practice.

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.

With aging of population and improvement of medical technology, the number of elderly patients receiving surgical treatment is increasing. Cardiovascular events after noncardiac surgery are one of the leading causes of death. Perioperative cardiovascular events have a high risk and incidence rate, thus severely affecting the prognosis of patients. In recent years, a growing number of studies have focused on the prevention and treatment of perioperative cardiovascular events in elderly patients. Assessing the risk of perioperative cardiovascular events and using effective interventions can effectively reduce the incidence of cardiovascular events and improve the prognosis of elderly patients. This article discusses cardiovascular risk assessment and management in elderly patients during noncardiac surgeries from the perspective of preoperative, intraoperative, postoperative periods, and perioperative medication used to provide assistance to clinical practice.

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.

For axial spondyloarthritis/ankylosing spondylitis, rehabilitation is very important for controlling disease activity, preventing disease progression and improving quality of life. Initiated by China Spine Alliance and jointly formulated by Air Force Specialty Medical Center and Chinese PLA General Hospital, the current guidelines were developed according to World Health Organization Guidelines Development Manual and the Basic Methods and Procedures for the Development/Revision of the Clinical Diagnosis and Treatment Guidelines, Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREEⅡ), Grading of Recommendations Assessment, Development and Evaluation (GRADE). Two basic princlples and 12 suggestions were made for important issues such as diagnosis, rehabilitation assessment, rehabilitation intervention and management for axial spondyloarthritis/ankylosing spondylitis.