Background Recent researches show that oxidative stress is involved in the progress of keratoconus.Nuclear factor-E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway plays a critical role in the defense against oxidative stress,but its function in keratoconus is unclear.Objective To investigate the differences of Nrf2-ARE signaling activation and matrix degenerating enzymes between keratoconus and normal corneal stromal cells.Methods Corneal stromal cells were isolated from keratoconus and normal cornea by using dispase and collagenase digestion.The cells were treated with hydrogen peroxide (H2O2) to mimic in vivo oxidative stress condition.Reactive oxygen species (ROS) production was measured by fluorescence substrate DCHF-DA incubation.Nrf2 level and the expression of Nrf2-ARE downstream antioxidant genes were analyzed by Western blot and real-time quantitative-PCR(RT-qPCR).The activity of matrix degenerating enzymes,including urokinase-type plasminogen activator (uPA)-uPA receptor (uPAR) system and matrix metalloproteinase-2 (MMP-2) were assessed by Western blot and gelatin zymography respectively.Results In normal culture,keratoconus corneal stromal cells assumed increased basal ROS and Nrf2 level when compared with normal cells(t =18.155,P＜0.01).However,after H2O2 treatment,the keratoconus corneal stromal cells showed increased ROS production,while decreased Nrf2 translocation and no significant difference in expression levels of Nrf2-ARE downstream antioxidant genes (Nrf2:t =62.123,P＜ 0.01 ; (nicotinamide adenine dinucleotide phosphate quinine oxidoreductase-1 [NQO-1]:t =2.209,P =0.092 ; hemo oxygenase-1 [HO-1]:t =0.293,P =0.784 ; superoxide dismutase [SOD2]:t =0.749,P =0.495).The contents of uPA-uPAR and the activity of MMP-2 also showed a higher level in keratoconus corneal stromal cells than normal cells,with significant differences between them (t =19.164,15.458,4.818,all at P＜0.01).Conclusions The defect of Nrf2-ARE signaling activation exists in the keratoconus corneal stromal cells,and correlats with the abnormal expression level of stromal degeneration enzymes,which suggests that the defect of Nrf2-ARE signaling activation may be involved in the progression of keratoconus.

Extracellular vesicles (EVs) are small bilayer lipid membrane vesicles that can be released by most cell types and detected in most body fluids. EVs exert key functions for intercellular communication via transferring their bioactive cargos to recipient cells or activating signaling pathways in target cells, and hence participate in the variety of diseases including the occurrence and development of liver diseases. In recent years, the prevalence of nonalcoholic fatty liver disease (NAFLD) has increased. Currently there is no reliable method except invasive liver biopsy for the diagnosis of liver inflammation or fibrosis staging. Therefore, the search for the corresponding markers of noninvasive circulation continues to be active, and extracellular vesicles are one of the most concerned. To this end, we reviewed current knowledge about the physical characteristics, biological components, and isolation methods of extracellular vesicles, and introduced the concept of using circulating cell-derived vesicles as a new diagnostic marker for nonalcoholic fatty liver disease.

Objective There are few researches for the serum betatrophin level and diabetic nephropathy (DN) recently.The aim of this study was to investigate the change of serum betatrophin level and the correlation of serum betatrophin and urinary albumin-to-creatintine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM).Methods A total of 150 Chinese subjects from Mar 2013 to Jul 2016 were enrolled in the study, including 90 patients with type 2 diabetes and 60 healthy controls.According to the level of UACR, the diabetic patients were divided into two groups:normal UACR group (UACR<30 mg/g, n=60) and abnormal UACR group(UACR>30 mg/g, n=30).Serum betatrophin was measured by enzyme linked immunosorbent assay (ELISA).UACR was measured by turbidimetric inhibition immune assay.Blood glucose blood lipid were measured simultaneously.Results The serum betatrophin level was significantly higher in abnormal UACR group than that in normal UACR group[677.37±59.02 vs 486.13±41.22 pg/mL, P<0.05];Serum betatrophin level in T2DM patients was positively correlated with age (r=0.246), waist hip ratio (WHR) (r=0.240), fasting blood glucose (FPG) (r=0.234), 2 hour plasma glucose (2hPG) (r=0.363), glycosylated hemoglobin (HbA1c) (r=0.346), fasting insulin (FINS) (r=0.249), insulin resistance index (HOMA-IR) (r=0.309), blood urea nitrogen (BUN) (r=0.223), creatinine (CREA) (r=0.277) and UACR (r=0.244) (P<0.05),and negatively correlated with glomerular filtration rate (GFR) (r=0.308) (P<0.01).Serum betatrophin level in normal UACR group was positively correlated with age, HbA1c and UACR (P<0.05);Serum betatrophin level in abnormal UACR group was positively correlated with WHR (r=0.504), 2hPG (r=0.600), HbA1c (r=0.449), HOMA-IR (r=0.395) (P<0.05).The WHR, HbA1c, HOMA-IR and GFR were the influential factors of the serum betatrophin level.Conclusion The level of serum betatrophin was significantly increased in T2DM patients with albuminuria, which suggests that the betatrophin might play an important role in the pathogenesis of DN.

Objective To detect serum oxytocin and highly sensitive C-reactive protein (hs-CRP) levels in obese and type 2 diabetes mellitus(T2DM) subjects and investigate the relationships between serum oxytocin levels and hs-CRP, glycolipid metabolism, insulin resistance and pancreas β cell function. Methods A total of 176 subjects were enrolled in the study, including 88 patients with newly-diagnosed type 2 diabetes ( T2DM) and 88 subjects with normal glucose tolerance(NGT). NGT and T2DM groups were further divided each into normal weight (NW) and obese(OB) subgroups. Obesity was defined as body mass index(BMI)≥25 kg/ m2 according to the WHO-Western Pacific Region diagnostic criteria (2000). 75g oral glucose tolerance test ( OGTT) was performed in all subjects. Fasting plasma glucose ( FPG), 2 h postprandial plasma glucose (2hPG), fasting insulin ( FINS), 2h postprandial serum insulin(2hINS), HbA1C and lipids were also determined. Insulin resistance and pancreas β-cell function were determined by homeostasis model assessment ( HOMA-IR, HOMA-β). Highly sensitive C-reactive protein(hs-CRP) level was determined by chemiluminescence immunoassay and fasting serum oxytocin level was determined by ELISA. Results Serum oxytocin level was lower in T2DM group than that in NGT group(P<0. 01), while serum hs-CRP level was higher in T2DM group than that in NGT group(P<0. 01). The level of serum oxytocin in subjects with obesity was also lower than that in subjects with NW in both NGT and T2DM groups [7. 16(6. 45-8. 82) vs 7. 98(7. 03-9. 17) ng/ L and 9. 23(8. 16-10. 36) vs 9. 86(8. 77-12. 06) ng/ L, P<0. 05]. The level of serum hs-CRP in subjects with obesity was higher than that in subjects with NW in both NGT and T2DM groups [0. 99(0. 25-1. 97) vs 0. 54(0. 19-0. 91) mg/ L and 3. 47(1. 63-6. 20) vs 1. 65(0. 81-3. 81) mg/ L, P<0. 05]. Serum oxytocin level was negatively correlated with hs-CRP, BMI, WC, WHR, HbA1C , FPG, 2hPG, FINS, 2hINS, total cholesterol, triglycerides, LDL-C and HOMA-IR, while was positively correlated with HOMA-β(P<0. 05). Subjects within the upper serum hs-CRP tertile had lower level of oxytocin when compared to subjects in the middle or lower serum hs-CRP tertiles(P<0. 05 ). Conclusion Serum oxytocin level was decreased in subjects with type 2 diabetes as well as with obesity. Serum oxytocin level was closely correlated with inflammation, glycolipid metabolism, insulin resistance, and pancreas β cell function. It may play an important role in the pathogenesis of obesity and T2DM.

ObjectiveTo investigate the prevalence of overweight or obesity in community patients with schizophrenia in Shanghai and to explore the related factors. MethodsStratified cluster sampling method was used and the general condition， physical examination and laboratory examination data of patients with schizophrenia who voluntarily participated in 2020 free health examination of National Basic Public Health Service were analyzed. ResultsA total of 3 200 patients were included into the study ，and the prevalence of overweight and obesity was 36.75% and 17.19%， respectively. Multivariate logistic regression analysis indicated that age between 40 and 60 （OR=1.333， 95%CI： 1.030‒1.724）， intake of first-generation antipsychotics （OR=1.413， 95%CI： 1.112‒1.796）， intake of second-generation antipsychotics （OR=1.573， 95%CI： 1.288‒1.921）， high-normal blood pressure （OR=1.549， 95%CI： 1.245‒1.927）， high-abnormal blood pressure （OR=2.824， 95%CI： 2.204‒3.619）， elevated ALT （OR=1.874， 95%CI： 1.386‒2.535）， elevated FBG （OR=1.270， 95%CI： 1.066‒1.513）， and elevated TG （OR=1.652， 95%CI： 1.335‒2.044） were the related factors that associated overweight or obesity in patients with schizophrenia. ConclusionOverweight and obesity are highly prevalent among community patients with schizophrenia in Shanghai. Age between 40 and 60， taking first-generation and second-generation antipsychotics， blood pressure higher than 120/80 mmHg， elevated ALT， elevated FBG， and elevated TG are associated with overweight or obesity in patients with schizophrenia. To provide personalized health guidance， medical staff in primary health care institutions should pay more attention to high-risk groups of overweight and obesity in schizophrenia patients at annual physical examination.