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 activation of ubiquitin proteasome system (UPS) and autophagy in brain tissues of rats after severe traumatic brain injury (sTBI) and the role of autophagy in secondary traumatic brain injury.Methods:(1) Twenty-five SD rats were randomly divided into sham-operated group, group of 3 h after sTBI, group of 1 d after sTBI, group of 3 d after sTBI and group of 7 d after sTBI ( n=5). Only bone window was opened in sham-operated group, and controlled cortical impact (CCI)-induced sTBI models were established in the other 4 groups. Western blotting was used to detect the expressions of free ubiquitin, ubiquitinated protein, vacuolar protein sorting 34 (VPS34), P62, microtubule-associated protein-light chain 3-II, and Mature-cathepsin D (CTSD). (2) One hundred SD rats were randomly divided into normal control group, sTBI group, lactacystin group and SAR405 group ( n=25). Ten μL lactacystin or SAR405 were stereotactically injected into the lateral ventricle of lactacystin group and SAR405 group, respectively; 30 min after that, CCI-induced sTBI models were established in the sTBI group, lactacystin group and SAR405 group. Three d after modeling, the expressions of ubiquitinated protein, LC3-II, P62, and Caspase-3 were detected by Western blotting; percentage of brain water content was determined by dry/wet weight ratio; neurological functions were assessed by modified neurological deficit scale (mNSS); degrees of brain tissue damage were detected by HE staining; and cerebral blood perfusion was detected by laser scattering hemodynamic imaging system. Results:(1) Compared with sham-operated group, group of 3 h after sTBI, group of 1 d after sTBI, group of 3 d after sTBI and group of 7 d after sTBI had significantly decreased free ubiquitin, and group of 1 d after sTBI, group of 3 d after sTBI and group of 7 d after sTBI had significantly increased ubiquitinated protein in the brain tissues surrounding the injury lesions ( P<0.05). Compared with sham-operated group, group of 3 d after sTBI and group of 7 d after sTBI had statistically increased VPS34 and Mature-CTSD and significantly decreased P62 and group of 1 d after sTBI, group of 3 d after sTBI and group of 7 d after sTBI had significantly increased LC3-II in the brain tissues surrounding the injury lesions ( P<0.05). (2) The ubiquitinated protein relative expressions in the brain tissues surrounding the injury lesions of normal control group, sTBI group, lactacystin group and SAR405 group were 4.78±2.63, 10.62±0.73, 13.45±1.22 and 8.50±0.83, respectively, with significant differences ( P<0.05). Compared with the normal control group, the sTBI group, lactacystin group and SAR405 group had significantly higher LC3-II, ubiquitinated protein and cleaved caspase-3/pro-caspase-3, and significantly lower P62 in the brain tissues surrounding the injury lesions ( P<0.05); compared with the the sTBI group, the lactacystin group had significantly higher LC3-II, ubiquitinated protein, and cleaved caspase-3/pro-caspase-3, and significantly lower P62 in the brain tissues surrounding the injury lesions ( P<0.05); compared with the the sTBI group, the SAR405 group had significantly lower LC3-II, ubiquitinated protein and cleaved caspase-3/pro-caspase-3, and significantly higher P62 in the brain tissues surrounding the injury lesions ( P<0.05). Compared with the normal control group([67.60±2.51]%、[0±0] scores、[333.41±46.86] PU), the sTBI group, lactacystin group and SAR405 group had statistically higher percentage of brain water content and mNSS scores ([80.2±1.30]%, [87.0±1.58]% and [71.60±1.81]%; 13.8±1.10, 16.4±0.55 and 10.40±1.14) and signficantly lower cerebral blood perfusion volume ([53.98±5.99] PU, [21.71±2.62] PU and [87.97±6.75] PU, P<0.05); compared with the sTBI group, the lactacystin group had significantly higher brain water content and mNSS scores, and significantly lower cerebral blood perfusion volume ( P<0.05); compared with the sTBI group, the SAR405 group had significantly lower brain water content and mNSS scores, and significantly higher cerebral blood perfusion volume ( P<0.05). HE staining showed that the cortical tissues were most severely damaged in the lactacystin group, followed by the sTBI group; the least damage was noted in the SAR405 group, and no significant damage in the normal control group was noted. Conclusion:After sTBI, UPS activation is earlier than autophagy; autophagy inhibition helps to alleviate UPS dysfunction, reduce Caspase-3-induced apoptosis, and is beneficial to the recovery of neurological function.

Objective To investigate the expression and significance of Src homology 2 domain-containing protein tyrosine phosphatase 2(SHP2)and phosphorylated SHP2(P-SHP2)in oxygen-induced retinopathy(OIR).Methods Twenty clean-grade C57BL/6J(B6)7-day-old neonatal mice were randomly divided into normal control group and OIR group,with 10 mice in each group.The mice in the normal control group and the nursing mother mice were fed together in a normal oxygen and room temperature environment.Mice in the OIR group were placed in an oxygen chamber with a temperature of 22-25 ℃,humidity of(60±10)％and oxygen volume fraction stable at(75±5)％for five days together with the nursing mother mice,and then transferred to a normal oxygen environment.At 12,14,17 days of age,three mice were selected from the normal con-trol group and the OIR group,respectively;and the expressions of SHP2 and P-SHP2 proteins in the retinal tissues of mice in the two groups were detected by Western blot.Two 17-day-old mice were randomly selected from the normal control group and the OIR group,respectively;and the retinal histopathology of mice was observed by hematoxylin-eosin staining.Results In the normal control group,the cell structure in all layers of the retinal tissue of 17-day-old mice was orderly,the inner limiting mem-brane and endothelial nucleus were intact,and the shape was normal.In the OIR group,the intercellular structure in all layers of the retinal tissue of 17-day-old mice was disordered,and the vascular endothelial nucleus was seen to break through the reti-nal inner limiting membrane.There was no statistically significant difference in the relative expression of SHP2 protein in the retinal tissues of mice at different ages in the normal control group(F=2.052,P＞0.05).The relative expression level of P-SHP2 protein in the retinal tissues of mice at 14,17 days of age in the normal control group was significantly lower than that at 12 days of age(P＜0.05),and the relative expression level of P-SHP2 protein in the retinal tissues of mice at 17 days of age was significantly lower than that at 14 days of age(P＜0.05).The relative expression level of SHP2 protein in the retinal tissues of mice at 14 days of age in the OIR group was significantly higher than that at 12,17 days of age(P＜0.05).There was no statistically significant difference in the relative expression level of SHP2 protein in the retinal tissues between 17-day-old mice and 12-day-old mice in the OIR group(P＞0.05).The relative expression level of P-SHP2 protein in the retinal tissues of mice at 14 days of age in the OIR group was significantly higher than that at 12,17 days of age(P＜0.05).There was no statistically significant difference in the relative expression level of P-SHP2 protein in the retinal tissues between 17-day-old mice and 12-day-old mice in the OIR group(P＞0.05).The relative expression level of SHP2 protein in the retinal tissues of mice at 12,17 days of age in the OIR group was significantly lower than that in the normal control group(P＜0.05).There was no statistically significant difference in the relative expression level of SHP2 protein in the retinal tissues of mice at 14 days of age between the two groups(P＞0.05).The relative expression level of P-SHP2 protein in the retinal tissues of 12-day-old mice in the OIR group was significantly lower than that in the normal control group(P＜0.05),while the relative expression level of P-SHP2 protein in the retinal tissues of 17-day-old mice was significantly higher than that in the normal control group(P＜0.05).There was no statistically significant difference in the relative expression level of P-SHP2 protein in the retinal tissues of mice between the two groups at 14 days of age(P＞0.05).Conclusion SHP2 and P-SHP2 are expressed with tem-poral fluctuations in OIR.Hypoxia may promote conformational changes of SHP2 in OIR mice,and play an active role in phos-phorylation;and participate in and promote the occurrence and development of OIR.

Objective To investigate the value of monocyte to lymphocyte ratio(MLR)and neutrophil percentage to albumin ratio(NPAR)in predicting diabetic macular edema(DME).Methods One hundred and one diabetic retinopathy patients admitted to the Third Affiliated Hospital of Xinxiang Medical University from January 2018 to February 2023 were selected as the research subjects,and they were divided into DME group(n=56)and non-DME group(n=45)based on fun-dus examination results.The general data such as gender,age,course of diabetes and laboratory indicators were collected by consulting medical records.Fasting elbow venous blood was collected early in the morning of the next day after the diagnosis of DME in both groups,the monocytes(MONO)count,lymphocyte(LYM)count,white blood cell(WBC)count,percentage of neutrophils(NEUT),plasma albumin(ALB),glycosylated haemoglobin(HbA1c)were measured by full automatic blood routine analyzer,and MLR,NPAR were calculated.General information and laboratory indexes of patients in the two groups were compared,and risk factors for DME were analyzed by multivariate logistic regression,and receiver operator characteristic(ROC)curve was applied to evaluate the predictive value of MLR and NPAR for DME.Results The course of diabetes,MONO count,NEUT,MLR,NPAR,WBC count,and HbA1c level of patients between the DME group were significantly higher than those in the non-DME group(P＜0.05);there was no statistically significant difference in gender,age,LYM count,and ALB level of patients between the two groups(P＞0.05).Multivariate logistic regression analysis showed that increased levels of WBC,MLR,and NPAR were independent risk factors for the occurrence of DME(P＜0.05).The ROC curve showed that the best cut-off value of MLR was 0.192,and the area under the curve(AUC)for the prediction of DME was 0.729(95％confidence interval:0.631-0.826),with a sensitivity of 58.9％and a specificity of 82.2％;while the best cut-off value of NPAR was 1.404,and the AUC for predicting DME occurrence was 0.884(95％confidence interval:0.820-0.949),with a sensitivity of 75.0％and a specificity of 91.1％;the AUC of MLR and NPAP for predicting the occurrence of DME was 0.906(95％confidence interval:0.851-0.906),with a sensitivity of 69.6％and a specificity of 93.3％.With MLR＞0.192 as positive and NPAR＞1.404 as positive,the parallel test of MLR and NPAR predicted the occurrence of DME with a sensitivity of 87.5％,a specificity of 71.1％,and an accuracy of 80.2％;while the tandem test of MLR and NPAR predicted the occurrence of DME with a sensitivity of 46.4％,a specificity of 97.8％,and an accuracy of 69.3％.Conclusion Increased levels of MLR and NPAR are independent risk factors for the occurrence of DME and have certain predictive value for DME.The predictive value of combined MLR and NPAR test for DME is higher than that of separate test,and parallel experiment is more helpful for the early prediction of DME.

Objective:This study aimed to explore the effect of Vaspin on adipose tissue macrophage polarization and its underlying mechanism.Methods:Fifty male SD rats, aged 8 weeks, were chosen and randomly allocated into three groups: the normal control(NC), the type 2 diabetes(T2DM), and various concentrations of Vaspin intervention(V1: 480 ng/kg, V2: 960 ng/kg, V3: 1 440 ng/kg). Vaspin was administered via intraperitoneal injection for 8 weeks. Glucose tolerance and insulin sensitivity were evaluated via intraperitoneal glucose tolerance test(IPGTT), intraperitoneal insulin tolerance test(IPITT) and hyperinsulinemic-euglycemic clamp. Adipose tissue inflammation and macrophage polarization were assessed using immunofluorescence, RT-PCR and western blotting.Results:After 8 weeks of intervention, there were no statistically significant differences in body weight and blood lipid levels among groups. IPGTT, IPITT, and hyperinsulinemic-euglycemic clamp experiments demonstrated that Vaspin intervention improved blood glucose and insulin sensitivity, exhibiting a dose-dependent manner( P<0.05). IF and RT-PCR showed that Vaspin downregulated the expression of CD11c, IL-1β, and TNF-α in eWAT, while upregulating the expression of CD206, IL-10, and PPARγ, which correlated with Vaspin concentration( P<0.05). ELISA revealed that Vaspin intervention reduced the concentrations of IL-1β and TNF-α in serum, while increasing the concentration of IL-10( P<0.05). Western blotting demonstrated that Vaspin downregulated iNOS protein expression, while upregulating Arg1, p-Akt, and PPARγ expression in a dose-dependent manner( P<0.05). Conclusion:Vaspin promotes M2 polarization of adipose tissue macrophages via PPARγ pathway, leading to reduced inflammation and improved insulin sensitivity in T2DM rats.

Objective To evaluate the predictive value of global longitudinal strain(GLS)measured by cardiac magnetic resonance(CMR)feature-tracking technique for left ventricular remodeling(LVR)after percutaneous coronary intervention(PCI)in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods A total of 403 patients undergoing PCI for acute STEMI were prospectively recruited from multiple centers in China.CMR examinations were performed one week(7±2 days)and 6 months after myocardial infarction to obtain GLS,global radial strain(GRS),global circumferential strain(GCS),ejection fraction(LVEF)and infarct size(IS).The primary endpoint was LVR,defined as an increase of left ventricle end-diastolic volume by≥20%or an increase of left ventricle end-systolic volume by≥15%from the baseline determined by CMR at 6 months.Logistic regression analysis was performed to evaluate the predictive value of CMR parameters for LVR.Results LVR occurred in 101 of the patients at 6 months after myocardial infarction.Compared with those without LVR(n=302),the patients in LVR group exhibited significantly higher GLS and GCS(P<0.001)and lower GRS and LVEF(P<0.001).Logistic regression analysis indicated that both GLS(OR=1.387,95%CI:1.223-1.573;P<0.001)and LVEF(OR=0.951,95%CI:0.914-0.990;P=0.015)were independent predictors of LVR.ROC curve analysis showed that at the optimal cutoff value of-10.6%,GLS had a sensitivity of 74.3%and a specificity of 71.9%for predicting LVR.The AUC of GLS was similar to that of LVEF for predicting LVR(P=0.146),but was significantly greater than those of other parameters such as GCS,GRS and IS(P<0.05);the AUC of LVEF did not differ significantly from those of the other parameters(P>0.05).Conclusion In patients receiving PCI for STEMI,GLS measured by CMR is a significant predictor of LVR occurrence with better performance than GRS,GCS,IS and LVEF.

Purpose To investigate the value of MYB and Notch1 immunohistochemical staining in the differential diagno-sis of classic adenoid cystic carcinoma of the breast(C-AdCC)and solid-basaloid adenoid cystic carcinoma of the breast(SB-AdCC).Methods MYB and Notch1 immunohistochemical staining were performed in 20 cases of C-AdCC,6 cases of SB-AdCC and 65 cases of other breast lesions in the archives of pa-thology department.26 cases of AdCC were detected by FISH,and 6 cases of SB-AdCC were detected by NGS.Results MYB immunohistochemical staining showed that C-AdCC(20/20)was moderately or strongly positive,while SB-AdCC(4/6)was mod-erately or strongly positive.Collagenous spherulosis(5/5)showed focal or diffuse weak positivity;Malignant adenomyoepi-thelioma(3/3)was focally moderately or strongly positive;8 matrix-producing carcinomas and 9 secretory carcinomas and 40 non-specific triple-negative breast cancers were negative.Immu-nohistochemistry of Notch1 showed diffuse moderate positive for SB-AdCC(3/6)and negative for C-AdCC(20/20).3 cases of malignant adenomyoepithelioma,5 cases of collagenous spherulo-sis,8 cases of matrix-producing carcinoma,9 cases of secretory carcinoma and 40 cases of non-specific triple-negative breast cancer were negative.FISH showed MYB gene disruption in C-AdCC(12/19)and NGS showed SB-AdCC(3/6)Notch1 muta-tion.Conclusion Moderately or strongly diffuse expression of MYB and Notch1 by immunohistochemistry can assist in the dif-ferentiation of C-AdCC from SB-AdCC,and it can be further clarified by molecular detection when it is difficult to distinguish malignant adenomyoepithelioma.

Objective:To explore the spatial support capacity and its influence in osteogenic effect of composite biofilm based on poly(propylene carbonate)(PPC)/poly(butylene succinate)(PBS)in rabbit tibial bone defect models,and to clarify its barrier functional reliability and osteogenetic effect in vivo.Methods:The composite biofilms of PPC/PBS and PPC/PBS/collegen type Ⅰ(Col-Ⅰ)(PPC/PBS/Co)were prepared.Eighteen Japanese big-ear rabbits were selected and two bone defects were prepared on each side of the tibia of the rabbits.Six rabbits were randomly selected to place PPC/PBS composite biofilm on the bone defects,2 rabbits were executed at 2,4,8 and 12 weeks after operation,and the surface microstructures of PPC/PBS composite biofilm in the rabhit bone defect area were observed by scanning electron microscope(SEM).The experiment was divided into blank control group,PPC/PBS composite biofilm group,BME-10X collagen membrane group,and PPC/PBS/Co composite biofilm group.The above biofilms were placed on the corresponding bone defects of rabbits by operation,while no biofilm was placed in the rabbits in blank control group.Three rabbits were killed at 2,4,8 and 12 weeks after operation respectively,and the gray values of regenerated bone in the bone defect areas of the rabbits in varrous groups were detected by soft X-ray;the fluorescence intensities of regenerated bone tissue in the bone defect areas of the rabbits in various groups were observed by laser scanning confocal microscope after fluorescence labeling.The pathomorphology of regenerated bone tissue in the bone defect areas of the rabbits in various groups were observed by HE staining and modified Gomori staining,and the expression levels of bone morphogenetic protein 2(BMP-2)and osteopontin(OPN)in the regenerated bone tissue in bone defect areas of the rabbits in various groups were detected by immunohistochemical staining.Results:In general,the PPC/PBS composite biofilm was tightly covered in the bone defect area without displacement and collapse.The SEM results showed that the porous surface of PPC/PBS composite biofilm appeared micropore structure and the number of micropores was increased with the prolongation of time,while the smooth surface of biofilm basically did not form the micropore-like structure.The results of soft X-ray detection showed that the gray values of regenerated bone tissue in bone defect areas of the rabbits in various groups were increased with the prolongation of time,and the gray value of regenerated bone tissue in bone defect areas of the rabbits in PPC/PBS/Co composite biofilm group was significantly higher than those in other groups(P＜0.05).The confocal micrscope results showed that the fluorescence intensity of regenerated bone tissue in bone defect areas of the rabbits in PPC/PBS/Co composite biofilm group was similar to those in blank control group at 4,8,and 12 weeks;compared with PPC/PBS composite biofilm group and BME-10X collagen membrane group,the fluoresence intensity of regenerated bone tissue in bone defect areas of the rabbits in PPC/PB/Co composite biofilm group at 4 weeks was increased(P＜0.05),and the fluoresence intensity of regenerated bone tissue in bone defect areas of the rabbits at 8 and 12 weeks were decreased(P＜0.05).The results of HE staining and modified Gomori staining showed that compared with PPC/PBS composite biofilm group and BME-10X collagen membrane group,the new bone formed faster in PPC/PBS/Co composite biofilm group and blank control group at 2 and 4 weeks,and the lamellar bone mineralization was higher at 12 weeks.The immunohistochemical staining results showed that compared with blank control group,PPC/PBS composite biofilm group and BME-10X collagen membrane group,the expression levels of BMP-2 and OPN proteins in the regenerated bone tissue in bone defect areas of the rabbits in PPC/PBS/Co composite biofilm group at 2 and 4 weeks were increased(P＜0.05 or P＜0.01);compared with blank control group and PPC/PBS composite biofilm group,the expression levels of BMP-2 and OPN proteins in the regenerated bone tissue in bone defect areas of the rabbits in BME-10X collage membrane group were decreased(P＜0.05 or P＜0.01).Conclusion:PPC/PBS composite biofilm has excellent spatial support capacity and reliable physical barrier function.The PPC/PBS/Co composite biofilm has a good effect in guiding bone regeneration in vivo.

Objective To evaluate the predictive value of global longitudinal strain(GLS)measured by cardiac magnetic resonance(CMR)feature-tracking technique for left ventricular remodeling(LVR)after percutaneous coronary intervention(PCI)in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods A total of 403 patients undergoing PCI for acute STEMI were prospectively recruited from multiple centers in China.CMR examinations were performed one week(7±2 days)and 6 months after myocardial infarction to obtain GLS,global radial strain(GRS),global circumferential strain(GCS),ejection fraction(LVEF)and infarct size(IS).The primary endpoint was LVR,defined as an increase of left ventricle end-diastolic volume by≥20%or an increase of left ventricle end-systolic volume by≥15%from the baseline determined by CMR at 6 months.Logistic regression analysis was performed to evaluate the predictive value of CMR parameters for LVR.Results LVR occurred in 101 of the patients at 6 months after myocardial infarction.Compared with those without LVR(n=302),the patients in LVR group exhibited significantly higher GLS and GCS(P<0.001)and lower GRS and LVEF(P<0.001).Logistic regression analysis indicated that both GLS(OR=1.387,95%CI:1.223-1.573;P<0.001)and LVEF(OR=0.951,95%CI:0.914-0.990;P=0.015)were independent predictors of LVR.ROC curve analysis showed that at the optimal cutoff value of-10.6%,GLS had a sensitivity of 74.3%and a specificity of 71.9%for predicting LVR.The AUC of GLS was similar to that of LVEF for predicting LVR(P=0.146),but was significantly greater than those of other parameters such as GCS,GRS and IS(P<0.05);the AUC of LVEF did not differ significantly from those of the other parameters(P>0.05).Conclusion In patients receiving PCI for STEMI,GLS measured by CMR is a significant predictor of LVR occurrence with better performance than GRS,GCS,IS and LVEF.

Neutrophil extracellular traps (NETs) are compounds composed of depolymerized DNA fibers and antimicrobial peptides released by neutrophils. NETs formation not only plays a role in pathological process of non-infectious diseases such as cystic fibrosis, systemic lupus erythematosus, diabetes and cancer, but also is closely related to many central nervous system diseases. In recent years, a large number of studies have found the presence of neutrophils and NETs in perivascular space of the infarcted lesions in patients with ischemic stroke (IS) and corresponding animal models. This article provides a review on NETs formation and clearance process, characteristics of NETs changes after IS, pathological processes involved in NETs after IS, and effects of NETs on neurons, to provide some references for IS.