Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Objective To explore the characteristics and evolution of disability prevention policies for the elderly by quantitative analysis and text-mining analysis of disability prevention policy texts for the elderly in China from 1988 to 2024,so as to provide a basis for improving disability prevention policies for the elderly in China.Methods CiteSpace 6.3.R1 and Rost CM6 software were used for bibliometric and text-mining analyses of policy texts related to the elderly disability prevention in China,such as policy quantity,issuing agencies,formats,and thematic changes.Results A total of 111 policy texts were analyzed,with only 5.4%(6/111)specifically focusing on elderly disability prevention.Policy development had 3 stages:1988-2005,an initial construction phase for the rehabilitation and prevention system,primarily focused on the establishment of fundamental systems for disability rehabilitation and basic institutional development,such as community security;2006-2015,a goal-oriented phase enhancing disability prevention and social security,particularly targeting fall prevention,chronic disease control,and subsidies for the elderly with disabilities;and 2016-2024,a phase of refined disability prevention strategies and integration with elderly health services,where the focus has increasingly shifted to precise prevention measures and the alignment of disability prevention with elderly health service systems.Conclusion China's disability prevention policy system and the policy system related to aging health have gradually formed,but the 2 have not been effectively integrated.While universal policies offer public awareness benefits,the lack of pertinent policies limits elderly disability prevention outcomes.It is necessary to introduce more pertinent elderly disability prevention policies.

Objective:To study the optimal anastomotic angle of end-to-side anastomosis autogenous arteriovenous fistula (AVF).Methods:A case-report and case-series design was used to obtain clinical data on 10 patients with diabetic nephropathy from Department of Nephrology, the 905th Hospital of the Chinese People′s Liberation Army Navy from June 2024 to February 2025. The models of "radial artery-cephalic vein" end-to-side anastomosis in the forearm with anastomotic angles of 30°, 40°and 50°were established. Numerical simulation was used to analyze the blood flow in the model, and to study the effect of different anastomotic angles on blood flow. Wall shear stress (WSS), cross section flow velocity and flow rate, and relative residence time (RRT) were studied in the model. The Whitney test with Holm correction was used to evaluate the difference in the median RRT between the three angle models.Results:At the moment of 0.65 s, the area fraction of low wall shear stress (LWSS) in the 30° model was 7.7%, which was reduced by 2.4% and 3.7% compared to the 40°and 50°models, respectively. At the time of 0.2 s, the area proportions of high wall shear stress (HWSS) in the 30°, 40°and 50°models were 54.4%, 43.9% and 37.4%, respectively. At 0.2 s, the maximum cross section flow velocity reached 4.07, 3.84 and 3.67 m/s for the 30°, 40°and 50°models, respectively. In the cycle, the maximum mean flow velocity for the 30°model reached 1.20 m/s. The mean flow rates of the 30°, 40°and 50°models in the J-5 cross section were 349, 316, and 328 ml/min, respectivly. For patient 6, the area proportions of the RRT>1 region were 11.97%, 14.84% and 15.22% for the 30°, 40°and 50°models, respectively.Conclusions:The optimal anastomotic angle of "radial artery-cephalic vein" for end-to-side anastomosis AVF surgery in patients with diabetic nephropathy is 40°.

Objective To explore the correlation between glycolysis related indexes of peripheral blood mononuclear cells(PBMCs)[glucose transporter 1(GLUT1),fructose-2,6-diphosphatase 3(PFKFB3)and lactate kinase M2(PKM2)]and intracranial pressure and clinical prognosis of patients with hypertensive cerebral hemorrhage(HICH)who broke into the ventricle.Methods 85 HICH patients hospitalized in our hospital from January 2021 to June 2022 were retrospectively collected as the research participants.The levels of PKM2,GLUT1 and PFKFB3 in PBMCs were analyzed by enzyme-linked immunosorbent assay kit.Six months after the onset of HICH,the short-term outcome was evaluated by modified Rankin scale(mRS),and the patients were divided into good prognosis(mRS score≤2)and poor prognosis(mRS score≥3).Results The levels of PKM2,PFKFB3 and GLUT1 in PBMCs of HICH patients with ventricular rupture were further lower than those of the patients without ventricular rupture(P<0.05).Six months after discharge,8 patients(22.9%)with HICH in non-ventricular rupture group had poor prognosis,while 28 patients(56.0%)with HICH in ventricular rupture group had poor prognosis,and the difference was statistically significant(χ2=9.263,P=0.002).Compared with the group with good prognosis,the levels of PKM2 and GLUT1 in PBMCs of HICH patients with poor prognosis were lower(P<0.05).Compared with the good prognosis group,the levels of PKM2 and GLUT1 in PBMCs of HICH patients with poor prognosis group were lower in HICH patients with ventricular rupture(P<0.05).In HICH patients who broke into the ventricle,the AUC of PKM2 and GLUT1 in predicting the poor prognosis of HICH patients were 0.879(95%CI:0.807～0.951)and 0.897(95%CI:0.831～0.963),respectively.Conclusion The levels of PKM2 and GLUT1 in PBMCs of patients with HICH breaking into ventricles decrease significantly,and are negatively correlated with intracranial pressure,which can be used to predict the short-term prognosis of the patients.

Objective To investigate the effect and underlying mechanism of roxadustat on apoptosis and senescence of renal tubular epithelial cell line HK-2 induced by heat stress.Methods After HK-2 cells were treated with different concentrations of roxadustat(10,20,30,40 and 50 μmol/L)for 24 h,CCK-8 assay was used to determine the optimal intervention concentration of roxadustat.HK-2 cells were divided into 4 groups(n=3):control group,roxadustat group(30 μmol/L,24 h),heat-stress group(43 ℃,2 h),and heat-stress+roxadustat group(30 μmol/L roxadustat treatmnet for 24 h followed by heat-stress 2 h).Cell viability was detected by CCK-8 assay.Expression of hypoxia-inducible factor-1α(HIF-1α),Cleaved Caspase-3,p16 and p21 at protein level was detected by Western blotting.Immunofluorescence assay was employed to observe the distribution of HIF-1α.β-galactosidase staining kit was utilized to detect SA-β-Gal activity.TUNEL staining was used to measure cell apoptosis.Results The highest cell viability was observed in the cells after 30 μmol/L roxadustat treatment.Heat stress resulted in a significant decrease in cell viability(P＜0.05),elevated protein levels of HIF-1α,Cleaved Caspase-3,p16 and p21(P＜0.05),enhanced SA-β-Gal activity(P＜0.05)and increased percentage of TUNEL-positive cells(P＜0.05)when compared with the cells in the control group.In comparison with the heat-stress group,the heat-stress+roxadustat group showed significant decrease in the protein levels of Cleaved Caspase-3,p16 and p21(P＜0.05),reduced activity of SA-β-Gal[(65.44±5.00)％vs(77.15±2.61)％,P＜0.05]and decreased percentage of TUNEL-positive cells[(16.73±2.20)％vs(46.40±13.87)％,P＜0.05],but increase in cell viability[(86.33±4.51)％vs(66.33±8.50)％,P＜0.05]as well as HIF-1α protein expression(P＜0.05).Furthermore,immunofluorescence assay showed that HIF-1α was mainly distributed in the nucleus and perinucleus.Conclusion Roxadustat attenuates heat stress-induced apoptosis and senescence of renal tubular epithelial cells by upregulating HIF-1α.

Objective    To compare the clinical outcomes of transcatheter aortic valve implantation (TAVI) in oncology and non-oncology patients with severe aortic stenosis (AS). Methods    A computer-based search in PubMed, The Cochrane Library, EMbase, CBM, CNKI and Wanfang databases from their date of inception to December 2021 was performed, together with reference screening, to identify eligible clinical trials. Two investigators screened the articles, extracted data, and evaluated quality independently. RevMan 5.3 and Stata 12.0 softwares were used for meta-analysis. Results    The selected 8 cohort studies contained 57 988 patients, including 12 335 cancer patients and 45 653 non-cancer patients. The results of meta-analysis showed that in patients with cancer, the 30-day mortality [OR=0.74, 95%CI (0.65, 0.84), I2=0%, P<0.000 01], stroke [OR=0.87, 95%CI (0.76, 0.99), I2=0%, P=0.04] and acute kidney injury [OR=0.81, 95%CI (0.76, 0.85), I2=49%, P<0.000 01] were lower than those in patients without cancer. The 1-year mortality [OR=1.46, 95%CI (1.15, 1.86), I2=62%, P=0.002] and late mortality [OR=1.51, 95%CI (1.24, 1.85), I2=61%, P<0.000 1] were higher in patients with cancer. Conclusion    It is effective and safe in cancer patients with severe AS undergoing TAVI. However, compared with patients without cancer, it is still high in long-term mortality, and further study of the role of TAVI in cancer patients with AS is necessary.

Objective:Upper gastrointestinal bleeding (UGIB) is a common gastrointestinal disease in the emergency department. Identifying low-risk patients suitable for outpatient treatment is the focus of clinical and research. A simple predictive model was developed to identify patients with UGIB who could safely avoid hospitalization, thus providing a feasible basis for triage by emergency physicians.Methods:A retrospective cohort study was conducted on patients with UGIB treated at Zhongda Hospital Southeast University from January 2015 to December 2020. Baseline demographic data and clinical parameters at the initial presentation were recorded. Multivariate logistic regression model was performed to identify predictors of safe discharge.Results:Six hundred and twelve patients (45.9%) were not safely discharged. There were significant differences in age, Charlson comorbidity index, systolic blood pressure, pulse rate, hemoglobin, albumin, blood urea nitrogen, creatinine and international normalized ratio between the safe discharge group and the non-safe discharge group ( P<0.05). Using multivariate logistic regression analysis, a total of 7 variables were included in the clinical prediction model of UGIB risk stratification: Charlson comorbidity index > 2, systolic blood pressure < 90 mmHg, hemoglobin < 10 g/dL, blood urea nitrogen ≥6.5 mmol/L, albumin <30 g/L, pulse ≥100 beats/min and international normalized ratio ≥1.5. The sensitivity, specificity, positive predictive value, and negative predictive value for predicting unsafe discharge were 98.37%, 24.10%, 52.3%, and 94.6%, respectively, with the best cutoff value ≥1. The area under the receiver operating characteristic (AUROC) curve was 0.822, which was significantly higher than Glasgow Blatchford score (GBS) 0.786 (95% CI: 0.752-0.820, P< 0.01) and AIMS65 0.676 (95% CI: 0.638-0.714, P< 0.01). Conclusions:The predictive model has a reliable predictive value, which can provide references for emergency medical staff to triage patients with UGIB, thereby reducing medical expenses and having certain social and economic benefits.

Objective:To understand the views of various relevant personnel on the standardized training mode of resident doctors after the implementation of Beijing′s medical education synergy policy, so as to provide references for further improvement of China′s medical education synergy policy.Methods:From January to May 2019, a semi-structured interview method was used to investigate the resident training students, clinical teachers(professional postgraduate tutors and resident training trainees′ guiding doctors)as well as resident training managers in 35 resident training bases in Beijing. The original data of the interviews were sorted out, coded and analyzed by taking root theory and main frame method descriptive analysis.Results:A total of 687 valid interview results were received, of which 71.86% of the resident training managers thought that the mode was more reasonable and the advantages outweighed the disadvantages; 38.07% of the resident training students and 45.45% of the graduate supervisors mentioned that the mode effectively shortened the training time of clinical talents; however, 31.98% of the resident training students and 22.92% of the resident training students′ guiding physicians mentioned it was difficult to balance courses, scientific research and clinical work under this mode, 61.62% of graduate supervisors pointed out that the students were lack of time and energy to engage in scientific research.Conclusions:The training mode of the integration of the standardized training of resident doctors and the postgraduate training of master′s degree in clinical medicine, given its necessity and institutional advantages, is found with room of improvement in its mode setting, arrangement of scientific research courses and clinical rotation, supervision and assessment of the process.

Objective: To explore the relationship between weight change and the changes in blood pressure, blood glucose and blood lipid profiles in middle-aged and elderly Chinese people. Methods: All participants were from the Dongfeng-Tongji cohort study. The study included 16 606 middle-aged and elderly Chinese people with complete information in the baseline survey in 2008 and the first follow-up survey in 2013. We collected the data on demographic characteristics, lifestyle, history of diseases and medication, and the results of medical health examinations, including height, weight, blood pressure, fasting blood glucose and lipid profiles. We divided the weight change into five groups, moderate or above weight loss (<-8.0%), slight weight loss (-8.0%, -3.1%), weight maintenance (-3.0%, 3.0%), slight weight increased (3.1%, 8.0%), and moderate or above weight increased (>8.0%). Generalized linear regression model was used to analyze the relationship between weight change and the changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG). Subgroup analyses were used to explore the influences of gender, age and baseline BMI level on the relationship between weight change and the above-mentioned metabolic indicators. Results: The average age of participants in baseline survey was (62.19±7.28) years with a range of 45 to 89 years. During the five-year period, there were 18.86% (2 633), 28.03% (4 655), 35.87% (5 956), 13.96% (2 319), 6.28% (1 043) people with moderate or above weight loss, slight weight loss, weight maintenance, slight weight increased, and moderate or above weight increased, respectively. Regression analyses showed that body weight change were positively correlated with changes in SBP, DBP, FBG, TC, LDL-C and TG, and negatively correlated with change in HDL-C (all linear trend P values were<0.05); As every 10% of weight changed, the β (95%CI) of changes in SBP (mmHg) (1 mmHg=0.133 kPa), DBP (mmHg), FBG (mmol/L), TC (mmol/L), LDL-C (mmol/L), HDL-C (mmol/L) and TG (mmol/L) were 4.94 (4.32, 5.55), 2.50 (2.11, 2.88), 0.05 (0.02, 0.08), 0.13 (0.11, 0.16), 0.14 (0.12, 0.16), -0.05 (-0.07, -0.04) and 0.16 (0.14, 0.18), respectively. Furthermore, subgroup analyses showed that weight change can lead to greater changes in blood pressure in older and overweight or obesity elderly people (all P for interaction<0.05). Conclusion Weight loss was beneficial for middle-aged and elderly people to improve the blood pressure, blood glucose and blood lipid profiles, regardless of the weight at the baseline, while weight gain was not.

Objective To investigate the effects of Physiotherapy in the prevention of lower extremitydeep venous thrombosis in patients with colorectal tumors after operation. Methods About 55 cases of inpatients admitted to the hospital from November 2014 to November 2015 were selected as the control group, and they were given routine nursing before and after operation. Another 55 cases of inpatients admitted to the hospital from November 2015 to November 2016 were selected as the observation group. On the basis of the control group, the observation group were treated with Physiotherapy in 24h after operation, 30min for once, twice/d, lasting for 7 days. The coagulation function , lower extremity deep venous flow velocity and the incidence of deep venous thrombosis in two groups were compared before operation and 7 days after operation. Result About 7 days after operation, levels of fibrinogen and D-dimer in the observation group were lower than those in the control group (P<0.01), the lower extremity deep venous blood flow velocity was higher than that in the control group (P<0.01), and the incidence of lower limb deep venous thrombosis was lower than that in the control group (all P<0.05). Conclusion Physiotherapy can improve the coagulation function in patients undergoing colorectal operation, improve the lower extremity deep venous flow velocity and reduce the incidence of lower extremity deep venous thrombosis.