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 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: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 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: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.

Hypoxic-ischemic brain damage is a serious complication of perinatal asphyxia. Enriched environment is the living condi-tions for the promotion of feeling, cognition and behavior. Enriched environment may promote the repairing of hypoxic-ischemic brain dam-age in term of praxiology, morphology and molecular biology, that enriched environment may regulate the secretion and release of various factors, and enhance synaptic plasticity, induce neuron regeneration, inhibit its apoptosis, and result in ethological and morphological recov-ery.

Objective To investigate the effect of electro-acupuncture pretreatment on content of interleukin (IL)-1βand IL-6 in serum and ischemic penumbra, and apoptosis in ischemic penumbra in rats after cerebral ischemia-reperfusion injury. Methods Thirty-six male Sprague-Dawley rats were randomly divided into sham group (n=12), model group (n=12), and electro-acupuncture pretreatment group (n=12). The middle cerebral arteries were occluded for 120 minutes and reperfused. Twenty-four hours after reperfusion, the level of IL-1βand IL-6 in serum and brain tissue was detected with enzyme-linked immunosorbent, and apoptosis of ischemic penumbra was detected with TU-NEL. Results The content of IL-1βand IL-6 in the serum and brain tissue, and the number of TUNEL-positive cells decreased in the elec-tro-acupuncture pretreatment group compared with that in the model group (P<0.01). Conclusion Electro-acupuncture pretreatment may in-hibit inflammatory response and apoptosis in cerebral ischemia-reperfusion injury.

[ ABSTRACT] AIM:To investigate the characteristics of the intestinal microbial flora in the pregnant women with congenital heart disease fetus ( PW group) and normal pregnant women ( NW group) .METHODS: Stool samples were collected from 15 NW and 17 PW cases.The bacterial genomic DNA was extracted.The 16S rDNA was amplified by PCR, and the second generation of Illumina sequencing was conducted.RESULTS: We obtained 2 696 276 ( NW group) and 2 445 530 ( PW group) optimized sequences.The coverage was greater than 97%.We obtained 77 243 operational taxono-mic units ( OTUs) in NW group and 75 600 OTUs in PW group after a 97%similarity merge.In NW group, the Chao 1 in-dex and the Shannon index were greater than those in PW group.The diversity analysis of microbial population indicated that they were mainly composed of Firmicutes, Proteobacteria and Actinobacteria.In family, the Bifidobacteriaceae and Cori-obacteriaceae were significantly different through analysis of variance.CONCLUSION: The Bifidobacteriaceae and Cori-obacteriaceae may play an important role in the occurrence of congenital heart disease.