Objective To explore the effect of SGLT2 inhibitor(SGLT2i)Dagaglipzin(Dap)on mitochondrial autophagy in cardiomyocytes in diabetic cardiomyopathy(DCM)by regulating mitochondrial membrane transporter TOM20.Methods H9C2 cardiomyocytes cultured in vitro were divided into normal control(Con)group,HG+PA group,knockout TOM20(HG+PA+siTOM20)group,knockout control(HG+PA+siNC)group,Dap intervention(HG+PA+Dap)group,and solvent control(HG+PA+DMSO)group.The expression of TOM20 was predicted by RNA-seq second-generation sequencing in HG+PA group.The expression of TOM20 and mitochondrial autophagy related proteins was detected by Western blot,the mitochondrial membrane potential was measured by immunofluorescence staining,and the mitochondrial autophagy level was evaluated by transmission electron microscopy.Results Compared with Con group,protein expressions of TOM20 and P62 were increased(P<0.05),while protein expressions of ULK1,Parkin,Beclin1 and LC3-B were decreased(P<0.05),mitochondrial membrane potential was destroyed,the number of mitochondrial autophagosomes was reduced,and autophagy activity was inhibited in HG+PA group.Compared with HG+PA+siNC group and HG+PA+DMSO group,the protein expressions of TOM20 and P62 were decreased(P<0.05),while the protein expressions of ULK1,Parkin,Beclin1 and LC3-B were increased(P<0.05),the damage of mitochondrial membrane potential decreased,the number of mitochondrial autophagosomes increased,and the inhibition of autophagy activity reversed in HG+PA+siTOM20 and HG+PA+DAPA groups.Conclusions SGLT2 inhibitors appear to partially restore mitochondrial function in diabetic cardiomyopathy by suppressing TOM20 expression,potentially through activation of mitochondrial autophagy.

Objective To explore the effect of SGLT2 inhibitor(SGLT2i)Dagaglipzin(Dap)on mitochondrial autophagy in cardiomyocytes in diabetic cardiomyopathy(DCM)by regulating mitochondrial membrane transporter TOM20.Methods H9C2 cardiomyocytes cultured in vitro were divided into normal control(Con)group,HG+PA group,knockout TOM20(HG+PA+siTOM20)group,knockout control(HG+PA+siNC)group,Dap intervention(HG+PA+Dap)group,and solvent control(HG+PA+DMSO)group.The expression of TOM20 was predicted by RNA-seq second-generation sequencing in HG+PA group.The expression of TOM20 and mitochondrial autophagy related proteins was detected by Western blot,the mitochondrial membrane potential was measured by immunofluorescence staining,and the mitochondrial autophagy level was evaluated by transmission electron microscopy.Results Compared with Con group,protein expressions of TOM20 and P62 were increased(P<0.05),while protein expressions of ULK1,Parkin,Beclin1 and LC3-B were decreased(P<0.05),mitochondrial membrane potential was destroyed,the number of mitochondrial autophagosomes was reduced,and autophagy activity was inhibited in HG+PA group.Compared with HG+PA+siNC group and HG+PA+DMSO group,the protein expressions of TOM20 and P62 were decreased(P<0.05),while the protein expressions of ULK1,Parkin,Beclin1 and LC3-B were increased(P<0.05),the damage of mitochondrial membrane potential decreased,the number of mitochondrial autophagosomes increased,and the inhibition of autophagy activity reversed in HG+PA+siTOM20 and HG+PA+DAPA groups.Conclusions SGLT2 inhibitors appear to partially restore mitochondrial function in diabetic cardiomyopathy by suppressing TOM20 expression,potentially through activation of mitochondrial autophagy.

Objective:To evaluate the efficacy and safety of anti-human T lymphocyte porcine immunoglobulin (P-ATG) with recombinant human tumor necrosis factor-α receptor Ⅱ:IgG Fc fusion protein (rhTNFR∶Fc, Etanercept) on grade Ⅲ/Ⅳ acute graft-versus-host disease (aGVHD) after allogenic hematopoietic stem cell transplantation (allo-HSCT) .Methods:Thirty-five patients with Grade Ⅲ/Ⅳ aGVHD who received P-ATG with etanercept therapy after allo-HSCT were retrospectively analyzed. P-ATGs (5 mg·kg -1·d -1) were administrated for 3 to 5 days, and then 5mg/kg was sequentially administrated, QOD to BIW. Etanercepts were administrated 25 mg, twice a week (12.5 mg, BIW for pediatric patients) . Results:Among the 35 patients with grade Ⅲ/Ⅳ aGVHD, 21 were males and 14 females, with a median age of 10 (3-54) years. A total of 19 cases of acute myeloid leukemia, 13 of acute lymphoblastic leukemia, 1 of severe aplastic anemia, 1 of myelodysplastic syndrome, and 1 of mixed phenotypic acute leukemia were noted. The overall response (OR) rate of P-ATG with etanercept was 85.7% (30/35) , with complete response (CR) and partial response (PR) rates of 34.3% (12/35) and 51.4% (18/35) , respectively, on day 28. The OR rate of grade Ⅲ aGVHD group was higher than of grade IV aGVHD group [100% (19/19) vs. 68.8% (11/16) , P=0.004]. On day 56, the OR rate became 77.2% (27/35) , with CR and PR rates of 62.9% (22/35) and 14.3% (5/35) , respectively. The OR rate of grade Ⅲ aGVHD group was also higher than of grade Ⅳ aGVHD group [89.5% (17/19) vs. 62.5% (10/16) , P=0.009]. Thirty-five patients had no adverse effects such as fever, chills, and rash during the P-ATG infusion, and no obvious liver and kidney function damage was observed after treatment. The main treatment-related complication was infection. The reactivation rates of CMV and EBV were 77.1% (27/35) and 22.9% (8/35) , respectively, and the bacterial infection rate was 48.6% (17/35) . With a median follow-up time of 13 (1-55) months after HSCT, the 1-year and 2-year OS rates were (68.1±8.0) % and (64.3±8.4) % , respectively. The 1-year OS rate of grade Ⅲ aGVHD group was superior to grade Ⅳ aGVHD group [ (84.2±8.4) % vs. (47.6±13.1) % , χ2=3.38, P=0.05]. Conclusion:This study demonstrated that P-ATG with etanercept was effective and safe in treating grade Ⅲ-Ⅳ aGVHD after allo-HSCT.

Inorganic arsenic (iAs) is a metalloid element that exists widely in the environment. Chronic iAs exposure may result in various types of cancer and chronic diseases. Although the mechanism of iAs toxicity is complicated, oxidative stress is the most crucial one that has been verified. Accumulating domestic and foreign epidemiological evidence shows that chronic iAs exposure through drinking water is strongly correlated with the prevalence of type 2 diabetes mellitus (T2DM). Mechanistic studies display that iAs exposure causes pancreaticβ-cell dysfunction and insulin resistance. The dynamic balance between reactive oxygen species (ROS) production and antioxidant response is one of the key factors maintaining normal physiological function. ROS plays a significant role in regulating glucose-stimulated insulin secretion and insulin signal transduction. This paper reviews the role of adaptive antioxidant response mediated by nuclear factor E2-related factor 2 ( Nrf2 ) in ROS signaling disorder resulted from chronic iAs exposure, and ROS signaling in the physiological function of pancreatic β-cell.

0.05). Conclusion This method is sensitive, accurate, stabile and is applicable to the determination of inorganic arsenic in groundwater samples.

Objective To know the distribution of arsenic and trace elements in drinking water in the endemic arsenism areas in Shanyin County, Shanxi Province. Methods Drinking water samples were collected from the chronic endemic arsenic poisoning areas of Silizhuang and Shanghexi, Shanyin County, Shanxi Province and HPLC-HG-AFS system was used to analyze the arsenic contents, valence and speciation. The trace elements were determined by ICP-MS. The data were analyzed by SPSS13.0 for windows. Results A total of 63 drinking water samples were determined, 39.68% of them exceeded the standard limit of arsenic level, inorganic arsenic was the main arsenical in drinking water, iAs3+/(iAs3++iAs5+) ratio was 56.17% in the water sample (arsenic was higher than 50 ?g/L) . The contents of Fe, Mn, Hg, Se and Pb in part of drinking water samples exceed the standard limits. No significant difference was seen between the arsenic results determined by HPLC-HG-AFS and ICP-MS. Conclusion Arsenic contamination of drinking water in Shanyin County, Shanxi Province is severe. The most frequently seen arsenic valence state in drinking water is iAs3+. Some trace elements in part of drinking water samples exceed the standard limits, this may aggravate arsenic poisoning.