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Most information used to evaluate diabetic statuses is collected at a special time-point, such as taking fasting plasma glucose test and providing a limited view of individual's health and disease risk. As a new parameter for continuously evaluating personal clinical statuses, the newly developed technique "continuous glucose monitoring" (CGM) can characterize glucose dynamics. By calculating the complexity of glucose time series index (CGI) with refined composite multi-scale entropy analysis of the CGM data, the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes (P for trend < 0.01). Furthermore, CGI was significantly associated with various parameters such as insulin sensitivity/secretion (all P < 0.01), and multiple linear stepwise regression showed that the disposition index, which reflects β-cell function after adjusting for insulin sensitivity, was the only independent factor correlated with CGI (P < 0.01). Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.
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Humans , Glucose , Blood Glucose , Insulin Resistance/physiology , Diabetes Mellitus, Type 2/diagnosis , Blood Glucose Self-Monitoring , Time Factors , InsulinABSTRACT
Objective:To evaluate and compare the efficacy and safety of ultra-rapid lispro insulin (URLi) and humalog lispro (HL) in the treatment of type 2 diabetes mellitus.Methods:This was an international multicenter, double-blind, randomized controlled study. From May 2019 to January 2021, a total of 481 patients with type 2 diabetes mellitus, who had been using insulin for at least 90 days and had poor glycemic control, were included. These patients were recruited from 34 research centers in China, including Shanghai Jiao Tong University School of Medicine Affiliated Sixth People′s Hospital. They were assigned to either the URLi group (319 patients) or the HL group (162 patients) using stratified blocked randomization. The primary endpoint was the change in hemoglobin A 1c (HbA 1c) relative to baseline after 26 weeks of treatment. Secondary endpoints included the proportion of patients who achieved HbA 1c<7.0% and ≤6.5% after 26 weeks of treatment, 1-h postprandial glucose (1hPG) or 2-h postprandial glucose (2hPG) excursions during a mixed meal tolerance test at week 26, as well as safety parameters. Continuous variables were compared using mixed model repeated measures or analysis of covariance, and categorical variables were compared using logistic regression or Fisher′s exact test. Results:Data based on the Chinese subgroup showed that there were no statistically significant differences between the URLi and HL groups in terms of male percentage [56.1% (179/319) vs. 56.2% (91/162); P=0.990], age [(59.5±8.4) vs. (59.6±9.3) years; P=0.839] and other baseline characteristics. Regarding the change in HbA 1c relative to baseline, the URLi group was non-inferior to the HL group (-0.59%±0.05% vs. -0.66%±0.06%; P=0.312). There were no statistically significant differences between the URLi and HL groups in proportion of patients who achieved HbA 1c<7.0% [47.3% (138/292) vs. 45.2% (70/155); P=0.907] and≤6.5% [27.7% (81/292) vs. 27.7% (43/155); P=0.816]. The excursions in 1hPG [(6.20±0.21) vs. (6.90±0.25) mmol/L; P=0.001] and 2hPG [(8.10±0.27) vs. (9.30±0.31) mmol/L; P<0.001] were lower in the URLi group than the HL group, with statistically significant differences. In terms of safety, there were no statistically significant differences in the percentage of subjects who reported treatment-emergent adverse events between the URLi and HL groups [49.8% (159/319) vs. 50.0% (81/162); P=1.000]. The event rate of nocturnal hypoglycemia was lower in the URLi group than the HL group, with statistically significant differences [(0.53±0.10) vs. (0.89±0.16) events per patient -year; P=0.040]. Conclusions:With good glycemic control, URLi showed non-inferiority for HbA 1c improvement versus HL and was superior to HL for postprandial glucose excursion control. Meanwhile the rate and incidence of nocturnal hypoglycemia were lower in the URLi group than the HL group.
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Objective:To investigate the protective effect of Momordica charantia polysaccharide (MCP) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice and the possible mechanism. Methods:MCP was extracted from Momordica charantia (MC). Fifteen C57BL/6J mice were randomly divided into three groups with five in each group: control group, DSS group and DSS+ MCP group. The body weight and disease activity index (DAI) of the mice were monitored every day. Mouse colon tissues and serum samples were collected. Pathological changes in intestinal tissues and the expression of inflammatory factors, CD4 + T cells, neutrophils and macrophages were analyzed by HE staining, ELISA, RT-qPCR and flow cytometry. Results:MCP alleviated the DSS-induced UC in mice by restoring body weight and stool consistency and reducing bleeding. Moreover, MCP could repair the mucosal barrier function of colon tissues, decreasing inflammatory cell infiltration and lessening the edema in mucosal layer and muscle layer, and therefore protect the damaged intestinal tract of mice. The expression of inflammatory cytokines (TNF-α and IL-1β) and the level of CD4 + T cells were decreased in the colonic tissues of MCP-treated mice. Conclusions:MCP ameliorated DSS-induced UC in mice through inhibiting weight loss, repairing colonic tissue damage, improving immune system disorder and decreasing the expression of inflammatory cytokines. This study provided reference for further study of MCP as a potential dietary intervention in the treatment of UC.
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BACKGROUND@#Little was known about the association among time in range (TIR), time above range (TAR), time below range (TBR), and cancer mortality among patients with type 2 diabetes. We aimed to investigate the association among TIR, TAR, TBR, and the risk of cancer mortality among patients with type 2 diabetes.@*METHODS@#A total of 6225 patients with type 2 diabetes were prospectively recruited in Shanghai, China. TIR was measured with continuous glucose monitoring at baseline and was defined as the average percentage of time in the target glucose range during a 24 h period. Cox proportion hazard regression analysis was used to determine the association between TIR and the risk of cancer mortality.@*RESULTS@#During a mean follow-up of 7.10 years, we confirmed 237 death events related to cancer. The multivariable-adjusted hazard ratio (HR) for cancer mortality was 1.32 (95% confidence interval [CI]: 1.01-1.75) in patients with TIR ≤70% compared with those with TIR >70%. When TIR was considered as a continuous variable, the multivariable-adjusted HR for cancer mortality associated with each 10% decrease in TIR was 1.07 (95% CI: 1.02-1.14). In the site-specific analysis, a significant association between TIR as a continuous variable and the risk of hepatocellular cancer was found (HR: 1.24; 95% CI: 1.09-1.41). However, no relationship between hemoglobin A1c and cancer mortality was observed (HR: 1.04; 95% CI: 0.97-1.10).@*CONCLUSIONS@#The present study found an inverse association of TIR with the risk of cancer mortality among patients with type 2 diabetes. New evidence of TIR was added into the clinical practice that TIR may be an optimal target of glycemic control among patients with type 2 diabetes.
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Humans , Blood Glucose , Blood Glucose Self-Monitoring , China , Diabetes Mellitus, Type 2/complications , Neoplasms , Prospective StudiesABSTRACT
Immunoproteasome is associated with various diseases such as hematologic malignancies, inflammatory, autoimmune and central nervous system diseases, and over expression of immunoproteasome is observed in all of these diseases. Immunoproteasome inhibitors can reduce the expression of immunoproteasome by inhibiting the production of related cell-inducing factors and the activity of T lymphocyte for treating related diseases. In order to achieve good efficacy and reduce the toxic effects, key for development of selective immunoproteasome inhibitors is the high selectivity and potent activity of the three active subunits of the proteasome. This review summarizes the structure and functions of immunoproteasome and the associated diseases. Besides, structure, activity and status of selective immunoproteasome inhibitors are also been highlighted.
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Objective To investigate the feasibility and clinical effect of the tubeless minipercutaneous nephrolithotomy (PCNL) in treatment of upper ureteral calculi.Methods From March 2014 to March 2015,all the patients with upper ureteral calculi except for those with severe infection,pyonephrosis or renal cortex less than 5 mm were randomized into two groups,the standard PCNL group (24 F nephrostomy tube) and the mini-PCNL group (18 F nephrostomy tube).After PCNL,all the patients received ultrasound examination to check residual stones,perforation and urine leakage.DJ tube was placed and the channel of PCNL was packed with hemostatic sponge without nephrostomy tube.There were 26 patients in standard group and 28 in mini-group.The operation time,postoperative hemoglobin change,postoperative visual analogue pain score (VAS),the time when urine turned clean,postoperative urinary extravasation,hydrothorax,fever and the stone-free rate were compared between two groups.Particularly,these data were compared in those aged＞65 years.Results The operation time in the standard PCNL and the mini-PCNL group was (58.3 ±21.8) and (86.4±23.3) minutes respectively,and had a significant difference (t=10.836,P＜0.05).The decrease in hemoglobin level was (8.3±5.8) g/L and (7.7±0.5.4) g/L,the VAS scores was (3.8±0.8) and (3.6±1.1),the time when urine turned clean was (11.9±4.7) h and (9.6±5.6) h,the postoperative hospital stay was (5.1±0.8) d and (4.8±1.2) d,and the stone free rate was 92.3％ and 89.2％ in standard PCNL and mini-PCNL group respectively(P＞ 0.05).No significant difference were found between two groups (all P＞0.05).There was one patient who got fever more than 38.5℃ in the standard group and 2 cases in the mini-group.Each group had 1 slight hydrothorax,and no blood infusion and perinephric urinary extravasation were found.The application of packing hemostatic sponge in the nephrostomy channel was feasible and suitable for both the standard and tubeless mini-PCNL groups.Conclusions The application of packing hemostatic sponge in the nephrostomy channel is feasible and suitable in both the standard and tubeless miniPCNL.It is safe for the treatment of renal and ureteral calculi,and it can decrease the hemorrhage and urine leakage,which works for the elderly patients too.
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Subacute thyroiditis can cause destruction of thyroid follicles and subsequent transient thyrotoxicosis.In cases of simultaneous occurrences of subacute thyroiditis and Graves' disease,the former may be missed and thus may further exacerbate thyrotoxicosis.Herein,we report in detail a case with abrupt onset of thyrotoxic heart disease when taking anti-thyroid medications,in order to call attention to the diagnosis and treatment of concomitant Graves' disease and subacute thyroiditis.
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ObjectiveTo investigate the clinical significance of Endothelin-1,Tumor necrosis factor-α and Intercellular adhesion molecule-1 in the patients with chronic obstructive pulmonary disease(COPD).MethodsThe serum samples were prepared from 80 cases with COPD and 30 healthy persons.The levels of ET-1,TNF-α and ICAM-1 were measured by enzyme-linked immunosorbent assay ( ELISA ).Results Levels of ET-1,TNF-α and ICAM-1 in the COPD patients were higher than thosein the healthy cases ( t =4.896,4.621,4.231,all P ＜ 0.05 ).Levels of ET-1,TNF-α and ICAM-1 in the period of AECOPD were higher than those in the cases of the COPD stable time( t =3.346,3.525,3.269,all P ＜0.05 ).ConclusionET-1,TNF-αt and ICAM-1 are involved in airway inflam mation,ET-1,TNF-α and ICAM-1 not only take part in the acute inflammation in COPD,but also closely connected with clinic stages.