Objective:To investigate the changes of proopiomelanocortin(POMC) expression in hypothalamus and corresponding metabolism in miR-21 knockout mice.Methods:miR-21 knockout or wild-type C57BL/6J mice were divided into diabetic group and control group, respectively. Diabetic mice model were forged with high-fat diet and low-dose streptozotocin. The changes of body weight and blood glucose in each group were monitored. By the end of the experiment, mice were sacrificed, and POMC protein expression and STAT3 mRNA expression in hypothalamus were detected.Results:There were no significant differences in body weight and blood glucose levels among all groups at baseline( P>0.05). The differences of body weight and blood glucose levels among various groups were compared at 3, 6, 9 and 12 weeks after the model was established. The results showed that body weight of mice in the diabetes group or miR-21 knockout+ diabetes group was higher than that in the control group at each time point( P<0.05). Moreover, there were significant difference in body weight between diabetes group and miR-21 knockout+ diabetes group at 3 and 12 weeks( P<0.05). The blood glucose levels in diabetes group were significantly higher than those in other groups at each time point( P<0.05). The blood glucose level in miR-21 knockout+ diabetes group was lower than that in diabetes group and higher than control group( P<0.05). POMC protein and STAT3 mRNA levels in diabetes group were significantly lower than those in control group, while those in the miR-21 knockout+ diabetes group were higher than those in the diabetes group. Conclusions:The expression of POMC in hypothalamus of miR-21 knockout mice is higher than that of wild-type diabetic mice. miR-21 knockout can decrease blood glucose level and body weight, and improve energy metabolism of diabetic mice.

Objective:To investigate the effects and mechanisms of curcumin on insulin resistance in streptozocin-induced diabetic rats.Methods:Diabetic rats were induced by intraperitoneal injection of STZ, then all the rats were randomly divided into diabetes (DM), diabetes+ curcumin (DM+ Cur), and diabetes + buffer control (DM+ NC) groups. Normal SD rats were used as control group (NC). The DM+ Cur group was treated with curcumin, while the DM+ NC group was treated with equal-volume buffer. The test lasted 12 weeks. The blood glucose was detected, and hyperinsulinemic-euglycemic clamp test was performed to estimate peripheral insulin resistance. At the end of the experiments, rats were killed and the total protein and cell membrane protein were extracted from skeletal muscle. The levels of phosphorylated PI3K, phosphorylated AKT, total PI3K, and total AKT were measured by Western blot. The levels of total GLUT4 and GLUT4 of cell membrane were also detected by Western blot, GLUT4 levels in skeletal muscle cell membranes were detected by immunofluorescence.Results:Blood glucose levels of DM+ Cur group were lower than those of DM group [(18.67±1.99 vs 24.38±2.88) mmol/L, P<0.05], and insulin resistance was also improved[the average GIR(14.69±0.29 vs 10.25±0.30) mg·kg -1·min -1, P<0.01]. The phosphorylation levels of PI3K and AKT were increased, and GLUT4 translocation to the cell membrane was increased. Conclusion:By activating the PI3K/AKT pathway, curcumin promotes GLUT4 translocation, increases skeletal muscle glucose uptake, and finally improves insulin resistance.

Objective:To explore the effect of subclinical hypothyroidism(SCH) on complications after coronary artery bypass grafting(CABG).Methods:The data of CABG patients hospitalized in TEDA International Cardiovascular Disease Hospital from January 2016 to December 2017 were retrospectively analyzed. According to the thyroid function after admission, the patients were divided into normal thyroid function group(NC group, 814 cases, 0.27 mIU/L≤TSH≤4.2 mIU/L) and subclinical hypothyroidism group(SCH group, 106 cases, TSH>4.2 mIU/L). The preoperative clinical data, surgical conditions, recent complications and one-year bridge stenosis rate were compared between the two groups in male or female.Results:Compared with NC group, SCH group had more female patients(53.8% vs 24.4%, P=0.000), lower smoking rate (38.7% vs 58.0%, P=0.000). There was no statistical difference in other baseline data and postoperative complications( P>0.05). Subgroup analysis depending on gender showed that the incidence of respiratory tract infection increased in female patients with SCH(10.5% vs 3.5%, P=0.034) compared with those in NC group, there was no significant difference in male. The TSH level was an independent risk factor for respiratory tract infection in female patients( OR=1.307, 95% CI=1.110-1.539, P=0.001). Compared with the male patients, the prevalence of hypertension(84.2% vs. 67.3%, P=0.041), diabetes mellitus(45.6% vs 16.3%, P=0.001), hospitalization time in ICU(44 h vs. 42 h, P=0.003), acute renal failure(10.5% vs 0, P=0.019) and massive blood transfusion(8.8% vs 0, P=0.034)increased. Conclusion:SCH appears to influence the postoperative outcome for female patients by increasing the development of postoperative respiratory tract infection.

Objective To analyze the correlation between urinary albumin/creatinine ratio (ACR) and 24-hour urinary microalbumin (UMA) and evaluate the predictive value of ARC for early diabetic nephropathy.Methods A total of 368 patients with type 2 diabetes mellitus were retrospectively collected.Early diabetic nephropathy was defined as 24h UMA 30～＜300 mg/24h.The correlation between ACR and 24hUMA,and the area under the receiver operating characteristic (ROC) curve of ACR in diagnosis of early diabetic nephropathy were calculated.Gender,age,course of disease,fasting venous blood glucose,glycosylated hemoglobin,blood pressure,triglyceride and total cholesterol were used as adjusting variables to establish univariate and multivariate logistic models of ACR for early diabetic nephropathy,respectively.A regression model was used to evaluate the diagnostic value of ACR for early diabetic nephropathy.Results The correlation between ACR and 24h UMA was 0.658.The area under ROC curve of ACR for early diabetic nephropathy was 0.907 before and 0.933 after adjustments of gender,age,course of disease,fasting venous blood glucose,glycosylated hemoglobin,blood pressure,triglyceride and total cholesterol,respectively.The OR value of ACR of diabetic nephropathy was 2.016 before and 2.762 after same adjustments.The calibration of Hosmer-Lemeshow chi-square test evaluation model was 19.362 before (P=0.13) and 14.928 after adjustments (P=0.061).Conclusion ACR is a better predictor for early diabetic nephropathy although its value is influenced by gender,age,course of disease,blood sugar,lipid,and blood pressure.

Cerebral hemorrhage is one of the refractory diseases which seriously endangers the safety of human life. Immune and inflammatory reaction participate in the whole process of cerebral hemorrhage, which can destroy the blood-brain barrier, accelerate brain edema, at the same time start and amplify the oxidative stress reaction, and aggravate the nerve function damage. After cerebral hemorrhage, many kinds of signal molecules are produced, which can activate the microglia and astrocytes around the hematoma, produce inflammatory factors and oxidizing mediators, and regulate the inflammatory response of the brain. Exploring the relationship between glial cell and immune, inflammatory responses is helpful to understand the mechanism of intracerebral hemorrhage intervention, find out a new target for the intervention of glial cells and develop new drugs and schemes for the treatment of intracerebral hemorrhage.

Objective To observe the changes of serum and fecal taurine-conjugated bile acid levels and its association with glucose metabolism during the spontaneous development of type 2 diabetes in OLETO rats.Methods Twenty male OLETF rats(4 weeks old)were included and 10 male LETO rats of the same age were used as the normal control group.OLETF rats were fed with high fat diet whereas LETO rats were fed with normal diet.Serum and fecal taurine-conjugated bile acid levels of OLETF rats were tested at different stage of diabetes including baseline, normal glucose tolerance, impaired glucose tolerance and diabetes periods, and the association of taurine-conjugated bile acid level with body weight, blood glucose, and glucose-regulating hormones were also investigated.Results Compared with LETO rats, the baseline serum levels of taurine-conjugated bile acid in OLETF rats did not change, but the levels of fecal taurine-conjugated bile acid including taurine-conjugated chenodeoxycholic acid(TCDCA), taurocholic acid(TCA)and taurine-conjugated deoxycholic acid(TDCA)were significantly decreased [(14.25±7.18 vs 0.90±0.31)mg/kg,(7.12±4.14 vs 1.30±0.35)mg/kg,(4.30±1.78 vs 1.02±0.14)mg/kg, all P<0.01].During the development of diabetes, the fecal levels of TCDCA, TCA and TDCA were still lower than those in the control rats.TDCA was negatively associated with the level of fasting blood glucose(r=-0.470, P=0.032),but positively associated with the serum level of glucagon-like peptide(GLP)-l(r=0.406, P=0.044).Conclusion The decrease of intestinal taurine-conjugated bile acid level is involved in the development of diabetes in OLETF rats.Intestinal TDCA may regulate the secretion of GLP-1 by paracrine pathway.

Objective To investigate the association of single nucleotide polymorphism (SNP) rs13333226 in uromodulin (UMOD) gene with diabetic kidney diseases (DKD) in Han population in Tianjin,China.Methods A total of 210 type 2 diabetes (T2DM),90 normal controls (NC) and 280 DKD patients were recruited.According to the level of estimated glomerular filtration rate (eGFR),the DKD subjects were further subdivided into three groups:GFR≥90 ml/min group (n=105),60 ml/mim≤GFR ＜ 90 ml/min group (n=84) and GFR ＜ 60 ml/min group (n=91).Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for UMOD rs13333226C genotyping.Results The frequencies of AA,GA,GG genotype were 27.8％,58.9％,13.3％ in NC group and 41.0％,48.6％,10.5％ in T2DM group and 54.3％,36.1％,9.6％ in DKD group.The frequency of G allele was 42.8％ in NC group,34.8％ in T2DM group and 27.7％ in DKD group.The genotype distribution of UMOD was statistically significant between NC group and DKD group,and between T2DM group and DKD group (P ＜ 0.05).G allele of UMOD was an independent protective gene polymorphism of DKD in Logistic regression (B=-0.248,Wald=8.012,P=0.021,OR=0.780,95％ CI 0.612-0.968).Conclusion The G allele of UMOD gene may be an independent protective factor of DKD in Han population in Tianjin,China.

Objective To explore the association of NH2-terminal pro-B-type natriuretic peptide ( NT-proBNP) with the risk of type 2 diabetes.Methods One hundred and twenty-six impaired glucose regulation( IGR) participants from Diabetic Identification Center of Tianjin Metabolic Diseases Hospital were included.NT-proBNP was measured in plasma samples collected from participants at baseline condition.Results At baseline, NT-proBNP was inversely associated with body mass index, waist circumference, fasting glucose, insulin and low-density lipoprotein-cholesterol( LDL-C) levels.During a follow-up of 2 years, 51 participants reported a new diagnosis of diabetes from OGTT.Baseline quartiles of NT-proBNP were inversely associated with diabetes risk, even after multivariable adjustment.Theadjustedrelativerisksfordiabeteswere1.0(reference),0.83(95%CI0.74-0.96),0.78(95%CI 0.68-0.90), 0.74 (95%CI 0.64-0.87) for the 1st, 2nd, 3rd, and 4th quartiles of baseline NT-proBNP, respectively ( P<0.01 ) .Conclus ion In IGRpopulation , lowlevels of NT-proBNP were associated with a significantly increased risk of type 2 diabetes.

[Summary] A total of 128 individuals with type 2 diabetes underwent continuous glucose monitoring for 3 consecutive days.The dawn phenomenon was defined by three different parameters according to the previous research:(1)the absolute increase of glucose level from nocturnal nadir to prebreakfast value(?G) above 20 mg/dl;(2)?G above 10 mg/dl;( 3 ) insulin requirement increased at least 20%.The participants were secondarily separated by presence/absence of a dawn phenomenon based on the definitions above.The impact on blood glucose fluctuation of different groups was assessed according to the standard deviation of blood glucose( SDBG) , the area under curve above 10 mmol/L ( AUC ) , and the mean amplitude of glycemic excursions ( MAGE ) , etc.The frequencies of dawn phenomenon were 64.8%(?G≥20mg/dl), 85.2%(?G≥10 mg/dl), and 59.4%(rise in insulin requirement≥20%)respectively.The impacts on SDBG, AUC, MAGE, and MODD were without statistical difference(P>0.05) between the presence and absence of the dawn phenomenon patients when?G≥10 mg/dl.However, the differences reached statistical significance(P<0.05) when ?G≥20 mg/dl and the increase in insulin requirement≥20%. Besides, the incidence of dawn phenomenon was positively correlated with HOMA-IR, HbA1C , and free C-peptide.Dawn phenomenon is a very frequent event in type 2 diabetes and not only impacts the overall glycemic control but also exaggerates glucose fluctuation.To be clinically relevant, ?G≥20mg/dl should be taken as the quantitative criterion of the dawn phenomenon.

T-cell exhaustion is characterized by the stepwise and progressive loss of T cell functions under conditions of antigen-persistence, which occurs following chronic infections and tumor outgrowth. Exhausted T cells present functional defects, express multiple inhibitory receptors and show reprogrammed transcriptional regulation. As T cell exhaustion is correlated to its dysfunction to control infections and tumors, exploring new strategies to target exhausted T cell may reverse this dysfunctional state and reinvigorate immune response. This study takes CD8+ T cell as an example, which acts as an important subset involved in exhaustion state, discuss current understanding of the properties of exhausted T cell and the mechanisms that promote and maintain this state, and reveal new therapeutic targets for chronic infection and cancer.