ObjectiveTo investigate the incidence of stroke in patients with type 2 diabetes mellitus (T2DM) in the community of Shanghai, and to explore its influencing factors. MethodsA two-way cohort study was used to observe the incidence of stroke in a dynamic cohort of14 743 community-based T2DM patients who were enrolled for management from January 2016 to December 2018 in Hongkou District, Shanghai. All the research subjects were followed up for 3 years to observe the stroke occurrence. Outcome events were retrospectively collected from the Shanghai Stroke and Acute Myocardial Infarction Registry Reporting Information System and the Cause of Death Registry System, and information on stroke onset and verification of past medical history were collected by family physicians through clinic follow-up, home follow-up, and telephone follow-up. Cox proportional hazards model was used to identify the risk factors of stroke in TDM2 patients, and the hazard ratio (HR) and its 95% confidence interval (CI) were calculated. ResultsAfter a mean follow up of 3.5 years, the standardized incidence of stroke in patients with T2DM was 8.65‰, and the risk of standardized incidence was 3.50 (95%CI: 3.26‒3.77) compared with that of the total national population. Cox proportional hazards regression analysis showed that age (HR=1.18, 95%CI: 1.13‒1.23), being female (HR=1.14, 95%CI: 1.01‒1.29), physical activity <600 metabolic equivalent (MET)·min·week^-1 (HR=1.24, 95%CI: 1.06‒1.44), substandard of HbA1c control (HR=1.16, 95%CI: 1.03‒1.30), occasional smoker(HR=1.23, 95%CI: 1.04‒1.45), and those who took insulin therapy (HR=1.36, 95%CI: 1.11‒1.66) were associated with an increased risk of stroke, while those received contracted services from family doctors were associated with a decreased risk of stroke(HR=0.78, 95%CI: 0.71‒0.88). ConclusionCommunity T2DM population in Shanghai has a high risk of stroke. It is necessary to continue to explore the positive role of family doctor contract service management model, strengthen individualized exercise, smoking cessation and other lifestyle interventions, and strictly control blood glucose as soon as one can to delay or avoid the occurrence of complications.

Objective To investigate the role and underlying mechanisms of oxoglutarate dehydrogenase-L(OGDHL)in renal fibrosis.Methods Twelve male wild-type C57BL/6J mice(8 weeks old,weighting about 25 g)were randomly divided into control group and model group(n=6).A mouse model of renal fibrosis was established by unilateral ureteral obstruction(UUO).HE staining,immunofluorescence assay,and immunohistochemical and Masson staining were applied to assess the extent of renal fibrosis.Human kidney-2 proximal tubule cell line(HK-2)were randomly divided into blank plasmid group(Vector),OGDHL overexpression group(OGDHL OE),blank plasmid+TGF-β1 treatment group(TGF-β1+Vector),TGF-β1 treatment and OGDHL overexpression group(TGF-β1+OGDHL OE).Transmission electron microscopy(TEM)was employed to observe mitochondrial morphology.RT-qPCR,Western blotting and immunofluorescence assay were used to detect the expression levels of OGDHL and mitochondrial metabolism-related genes.Adenosine triphosphate(ATP)level,oxygen consumption rate(OCR),extracellular acidification rate(ECAR)and other mitochondrial metabolism-related indicators were detected with corresponding reagent kits and Agilent Seahorse.Results UUO operation resulted in obvious thinning of the renal cortex,significant hydronephrosis.HE staining revealed that tubular atrophy accompanied by dilated tubular lumens in the kidneys.Immunofluorescence,immunohistochemical and Masson staining showed obvious renal fibrosis after UUO operation.In the mouse model of renal fibrosis,the expression of OGDHL was decreased by 82.9%at mRNA level(P<0.001)and 81.9%at protein level(P<0.001),the production of mitochondrial ATP was reduced by 0.970±0.151 μmol/L(P<0.01),and notable damaged mitochondrial structure was observed,with maximum breathing capacity decreased by 25.260±1.920 pmol/min(P<0.001),expression levels of fatty acid oxidation-related genes were declined by 50.2%(P<0.05),while glycolysis was enhanced,with the genes related to glycolysis increased by 2.5 times when compared with those in the control group(P<0.05).After OGDHL overexpression,mitochondrial morphological damage was significantly improved,ATP production was increased by 0.980±0.090 μmol/L(P<0.05),with significantly alleviated energy metabolism disorder and renal fibrosis(P<0.05).Conclusion OGDHL regulates mitochondrial metabolic reprogramming of renal tubular epithelial cells to alleviate fibrosis,suggesting that OGDHL may be a new therapeutic target for renal fibrosis.

ObjectiveTo analyze the incidence， recovery rate and associated factors of nonalcoholic fatty liver disease （NAFLD） among residents aged 65 years old and above in Xinqiao Community of Songjiang， Shanghai， and to provide basic data for further efficient community management. MethodsData of annual geriatric physical examination program for residents aged 65 and above were collected in Xinqiao Community， Songjiang from 2016 to 2022. Those residents who participated twice or more were included in this analysis. Data were collated into longitudinal form. For each participant， data of the first physical examination was used as baseline， and each subsequent examination was taken as follow-up. Incidence and recovery rate of NAFLD were calculated. Cox proportional hazard models were used to explore the associated factors and their changes with the onset and recovery of NAFLD. ResultsDuring the study period， a total of 11 983 residents participated in physical examinations， of which 8 644 participated twice or more， and 8 154 had no history of excessive alcohol consumption. B-ultrasound showed that there were 5 267 residents without NAFLD and 2 887 with NAFLD at baseline. After a median follow-up of 3.3 years， the incidence density of NAFLD in this population was estimated to be 11.5 per 100 person-years， and the recovery density was 23.4 per 100 person-years. The incidence density of NAFLD was negatively associated with age， and positively associated with baseline BMI， abdominal obesity， high fasting blood glucose， and high triglycerides. The recovery density was negatively associated with baseline BMI and abdominal obesity. Compared with those with normal BMI at both baseline and follow-up， those with persistent obesity showed the highest risk of NAFLD （males： HR： 3.19， 95%CI： 2.16-4.70； females： HR： 3.34， 95%CI： 2.46-4.54） and the lowest potential of recovery （males： HR： 0.58， 95%CI： 0.42-0.82； females： HR： 0.58， 95%CI： 0.44-0.77）. Persistently high triglycerides were also associated with a higher risk of developing the disease. ConclusionResidents aged 65 years old and above in Xinqiao， Shanghai had a higher incidence and recovery rate of NAFLD. Women， being obese and having hyperlipidemia are at a higher risk for the development and persistence of NAFLD.

Urine nontargeted metabolomics technology was developed for investigating the effect and mechanism of improving learning and memory ability in APP/PS1 mice of Psoralea corylifolia. All animal experiments were approved by the Animal Ethics Committee of Heilongjiang University of Chinese Medicine (Approval No.: 2020092502). Sixteen APP/PS1 mice were randomly divided into the model group and Psoralea corylifolia group (0.5 g·kg^-1), and eight male C57BL/6J mice of the same background were selected as control group, step-through test and novel object recognition were used as evaluation indexes. Changes in urine endogenous metabolites of mice from eachgroup were determined by ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS), and differential metabolites were screened, and metabolic pathway enrichment analysis was performed. The results of pharmacodynamic investigation showed that Psoralea corylifolia can reduce the dark incubation period and number of errors in APP/PS1 mice (P < 0.01) and improve the new object recognition index of APP/PS1 mice (P < 0.01). Metabolomics analysis identified 15 differential metabolites, and 9 differential metabolites were significantly call back by Psoralea corylifolia. Metabolic pathway analysis showed that histidine metabolism, citric acid cycle, taurine and hypotaurine metabolism and glucose metabolism were the main metabolic pathways of Psoralea corylifolia in improving learning and memory ability. These studies suggest that Psoralea corylifolia improves the learning and memory ability of APP/PS1 mice, and its mechanism may be related to improving mitochondrial dysfunction, reducing peripheral histamine level, regulating energy metabolism disorders and antioxidant levels.

Objective:To investigate the prevalence and mortality of dementia and assess the impact of geriatric syndromes (GS) on the risk for dementia and death in elderly population in Beijing.Methods:A cross-sectional survey was conducted in the elderly population aged ≥65 years and selected by a multi-stage sampling in Beijing during 2013-2015. Cognitive function was screened using the Chinese Revised Version of the Mini-Mental State Examination (MMSE). Then, neurological examination and psychiatric assessment were performed for those with the MMSE score lower than the cut-off value. The information about GS prevalence was also collected. The study also collected death records for all individuals from baseline until December 31, 2019. Based on the age and gender distribution from Beijing data of the 2010 Six th National Population Census, the dementia prevalence in the study population was directly standardized. Logistic regression analysis was used to evaluate the association of different forms of dementia with GS, and Cox proportional hazards regression model was used to estimate the hazard ratio ( HR) and 95% CI of death. Results:During 2013-2015, a total of 2 935 individuals completed dementia assessments, of which 167 were diagnosed with dementia. The standardized prevalence of dementia was 5.9% (95% CI: 5.0%-17.4%). The individuals with Alzheimer's disease (AD) and vascular dementia (VaD) accounted for 58.7% and 28.1% of total individuals with dementia, respectively. Aging, lower education level, urinary incontinence, and fall were risk factors for AD, while disability of activity of daily life dependence, hypertension, and stroke were found to be risk factors for VaD. After a median follow-up of 5.44 person-years, 399 deaths were recorded. The 5-year mortality risk was 2.87 (95% CI: 1.92-4.17) times and 4.93 (95% CI: 3.23-7.53) times higher for the elderly individuals with AD and VaD, respectively, compared to non-demented individuals. After adjusting for demographic, GS, and cardiovascular risk factors, the mortality risk in the elderly individuals with AD showed no significant difference compared with non-demented individuals ( HR=1.32, 95% CI: 0.89-1.97), while the mortality risk in those with VaD was 2.46 (95% CI: 1.49-4.05) times higher than that in non-demented individuals. Conclusions:The prevalence of dementia in Beijing increased significantly in the context of population aging, especially the prevalence of AD. The presence of GS increased the risks for AD and VaD, as well as the risk for death. Close attention needs to be paid to GS management in dementia prevention in elderly population.

Objective To develop and validate a machine learning (ML)model based on serum Klotho protein that can accurately predict all-cause mortality in chronic kidney disease (CKD ) patients.Methods A retrospective cohort trial was conducted on all the non-dialysis adult patients diagnosed with CKD stages 1～5 in our department from February 7,2012 to October 18,2019.They were assigned into a training set and an internal validation set in a ratio of 7:3.A total of 47 clinical features,including serum Klotho protein level,were used as variables to inform these models.Based on the training set,univariate Cox regression model was employed to screen out the possible risk factors for all-cause mortality,and Lasso-Cox regression model was further applied for the screening.Then multivariate Cox stepwise regression analysis was conducted to develop a nomogram risk prediction model for all-cause mortality,and the model performance was evaluated through internal validation.Results There were totally 400 patients enrolled in this trial,and 280 of them (including 52 dead and 228 survival)were assigned into the training set and other 120 (including 21 dead and 99 survival)into the validation set.For the constructed 5-year all-cause mortality risk prediction model,the area under the curve (AUC)value was 0.760 (95％CI:0.676～0.844)in the training set and 0.788 (95％CI:0.679～0.897)in the validation set,and the overall C-index was 0.755 (95％CI:0.685～0.826)and 0.720 (95％CI:0.614～0.826),respectively in the 2 sets.Univariate Cox regression analysis showed that age,history of cardiovascular disease(CVD),cystatin C(Cys-C),alkaline phosphatase (ALP),albumin,eosinophil (EOS)count,hemoglobin (Hb),complement C3,calcium,C-reactive protein (CRP),TNF-α and serum Klotho protein may be predictive factors for all-cause mortality (P<0.05).Multivariate Cox stepwise regression analysis finally screened age,albumin,complement C3 and serum Klotho protein as independent predictors (P<0.05).Based on these 4 predictors,a risk prediction model for all-cause mortality was constructed and validated.Conclusion A Klotho-based risk ML model for predicting all-cause mortality in CKD patients is successfully developed and validated.Advanced age is a risk factor,and higher albumin,complement C3 and serum Klotho protein levels are protective factors for all-cause mortality in CKD patients.

Objective To investigate the correlation between complement C3,C4,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR)and disease activity of systemic lupus erythematosus(SLE).Methods A total of 69 SLE patients admitted to the hospital from January to December 2021 were selected as the SLE group,and 70 healthy individuals were selected as the control group during the same period.The changes of serum related indicators were compared between the SLE group and the control group.According to systemic lupus erythematosus disease activity index(SLEDAI),SLE patients were divided into mild active group(27 cases)and moderate and severe active group(42 cases).The changes of related indicators were compared between the two groups.Spearman correlation analysis was used to analyze the correlation between SLEDAI score and serum related indicators.Receiver operating characteristic(ROC)curve was used to ana-lyze the validity of diagnosis of disease severity.Results Compared with the control group,the levels of serum complement C3 and C4 in the SLE group were decreased,and the levels of CRP and ESR were increased,the differences were statistically significant(P＜0.05).Compared with the mild group,the levels of serum com-plement C3 and C4 in the moderate and severe group were decreased,and the levels of CRP and ESR were in-creased,and the differences were statistically significant(P＜0.05).The SLEDAI score of SLE patients was positively correlated with serum CRP and ESR levels(P＜0.05),and negatively correlated with serum com-plement C3 and C4 levels(P＜0.05).The area under the curve(AUC)of CRP,ESR,complement C3 and C4 were 0.716,0.875,0.872 and 0.856,respectively,the sensitivity were 59.52％,85.71％,78.57％and 78.79％,respectively,and the specificity were 79.83％,81.67％,86.79％and 86.54％,respectively.Conclu-sion Serum complement C3,C4,CRP and ESR are correlated with the progression of SLE,and play auxiliary roles in the disease activity stage of SLE.

Objective:To explore therapeutic efficacy and mechanism of puerarin(PUE)in treating of ulcerative colitis(UC).Methods:Network pharmacology and molecular docking technique were used to screen and analyze targets of PUE in regulating UC.C57BL/6 mice were given free access to 2.5%DSS aqueous solution for 7 days,and influence of PUE on changes in body weight and disease activity index(DAI)score were subsequently observed.Histopathological alterations of colon tissue were observed by HE staining,changes of goblet cell population in colon tissue were evaluated through Alcian blue staining;expressions of inflammatory factors in colon tissue were detected by qRT-PCR and ELISA.Effect of PUE on MODE-K cell viability and apoptosis were assessed by CCK-8 and flow cytometry.Results:A total of 38 common targets of PUE in modulating UC,such as AKT1,TNF,STAT3,CASP3,HIF1A and etc,mainly involving TNF,IL-17 and PI3K-Akt signaling pathway.In vivo experiments confirmed that PUE ameliorated degree of colon shortening,body weight and DAI scores and reduced inflammatory cell infiltration in mice.Besides,expressions of inflammatory factors in colon,such as TNF-α and IL-1β,were inhibited by PUE.Furthermore,in vitro experiments validated that PUE relieved DSS-induced apoptosis of epithelial cells.Conclusion:PUE alleviates occurrence and development of DSS-induced UC in mice.