目的·建立小鼠持续葡萄糖监测(continuous glucose monitoring,CGM)技术,并对其血糖时间序列进行多尺度熵(multiscale entropy,MSE)分析.方法·选取饮食诱导肥胖型(diet-induced obesity,DIO)小鼠(n=3,DIO组)及对照组小鼠(n=3)为研究对象,利用全植入式血糖遥测系统分别收集2组小鼠的血糖及体温数据,取术后第10-14日数据进行分析,并统计系统的记录时间.利用MATLABR2019b软件对2组小鼠术后第11?17日的血糖时间序列进行MSE分析,计算每个时间尺度上对应的熵值.结果·成功建立了以全植入式血糖遥测系统为基础的小鼠CGM技术.6只小鼠的平均记录时间为(27.3±9.3)d,共获得232 887个血糖数值.DIO组小鼠平均血糖水平为(7.04±0.71)mmol/L,平均体温为(33.34±0.18)°C.与对照组相比,DIO组小鼠血糖时间序列复杂度较低,但差异无统计学意义.结论.成功建立了小鼠CGM技术;MSE分析发现,DIO型小鼠血糖时间序列复杂度降低,可能县S早期糖代谢异常的表现之一?

Here, we studied the metabolic function of LAMTOR1 from macrophages using LAMTOR1 macrophage-specific knockout (MKO) mice. LAMTOR1 MKO mice showed resistance to high-fat diet (HFD)-induced obesity, lipid steatosis, and glucose metabolic disorders, with elevated levels of pro-inflammatory cytokines. The energy expenditure, oxygen consumption, and CO 2 production increased significantly in HFD-fed MKO vs. wild-type (WT) mice. HE and immunohistochemistry staining showed a remarkable CD68 + Kupffer cell accumulation in the liver. Additionally, flow cytometry revealed that the proportion of macrophages and monocytes increased significantly in the liver of MKO mice. Of note, these macrophages were probably derived from the bone marrow since the proportion of CD11b + cells as well as the proliferative activity was also increased in the context of femoral bone marrow cells. In addition, the Kupffer cells of both WT and KO mice were double-positive for the M1 (CD86) and M2 (CD206) markers. However, the expression of both M1 and M2 macrophage-related genes was increased in the liver of HFD-fed KO mice. Murine primary hepatocytes and Kupffer cells were further isolated and incubated with oleic acid for 24 h. The glucose output of primary hepatocytes from MKO mice was not affected. However, decreased lipid tolerance was observed in LAMTOR1-deficient Kupffer cells. Overall, our results suggest that LAMTOR1 deficiency in macrophages prevents obesity and metabolic disorders via the accumulation of Kupffer cells in the liver and the consequent hyper-inflammation and increased energy expenditure. Therefore, our results provide a new perspective for macrophage-derived LAMTOR1 in the context of systemic metabolism.

结合上海交通大学医学院的线上教学模式,探讨成果导向教育(Outcome Based Education,OBE)对运用MOOC加强培养医学学术型研究生创新能力的启示.

Atherosclerotic cardiovascular disease remains the leading cause of death among patients with diabetes. Early identification of subclinical atherosclerosis is essential for the management of diabetic patients. This study aimed to characterize serum metabolic signatures associated with carotid intima-media thickness (C-IMT), a proxy of subclinical atherosclerosis, in patients with type 2 diabetes mellitus (T2DM). After 1:1 matching by sex, age, body mass index, glycated haemoglobin A1c, and other clinical parameters, a total of 462 T2DM patients were enrolled, consisting of 231 patients with C-IMT of ≥ 1 mm (abnormal C-IMT) and 231 patients with C-IMT of < 1 mm (normal C-IMT). C-IMT was assessed using ultrasonography. The serum metabolic profiling of fasting blood samples was performed using liquid chromatography-tandem triple quadrupole mass spectrometer coupled with the multivariate and univariate statistical analysis. Patients with abnormal C-IMT had significantly higher deoxycholic acid (DCA) and taurodeoxycholic acid (TDCA) levels, and lower levels of taurocholic acid (TCA) than those with normal C-IMT. Conditional logistic regression analysis revealed that per 1-standard deviation increase of DCA, TDCA and TCA were significantly associated with 64.7% (95% CI: 1.234–2.196) and 38.5% (95% CI: 1.124–1.706) higher, and 26.8% (95% CI: 0.597–0.897) lower risk of abnormal C-IMT, after adjustment of confounders. The addition of DCA, TCA, or DCA × TDCA/TCA ratio significantly improved the discrimination of abnormal C-IMT over traditional risk factors. Serum bile acids may be potential biomarkers for subclinical atherosclerosis in T2DM patients, which needs further confirmation.

•Growth differentiation factor 15 (GDF15) levels significantly decreased after 4 weeks of lifestyle intervention (LI).•The change of GDF15 levels between week-4 and baseline were negatively associated with the baseline GDF15 levels.•The effect of LI on the decrease of GDF15 levels was more significant among patients with baseline GDF15 levels ≥900 pg/ml.

血清1,5-脱水葡萄糖醇(1,5-anhydroglucitol,1,5-AG)是一项反映既往1～2周内血糖情况的糖尿病管理新指标,近年来有较多研究探索其用于糖尿病早期筛查和科学管理的价值及临床意义.唾液作为一种无创的生物样本,其1,5-AG水平在糖尿病筛查中的应用也初见端倪.未来1,5-AG在临床进一步推广应用尚需开展的研究包括:确立正常参考值范围、大型前瞻性研究明确其预测结局及指导治疗的优势、建立唾液1,5-AG的便捷性检测方法 等.

Abstract Background Clinical and basic investigations have indicated a significant association between circulating growth differentiation factor 15 (GDF15) and cardiovascular disease; however, the relationship between GDF15 and lower extremity atherosclerotic disease (LEAD) has been less studied. The present study aimed to explore the association between GDF15 and LEAD in Chinese patients with type 2 diabetes mellitus (T2DM). Considering that obesity is an important factor associated with circulating GDF15 levels, whether the relationship between serum GDF15 levels and LEAD is affected by body mass index (BMI) was also analysed. Methods A total of 376 hospitalized T2DM patients were enrolled (161 with LEAD and 215 without LEAD). A sandwich enzyme-linked immunosorbent assay was used to detect the serum GDF15 levels. The femoral intima-media thickness (F-IMT) and LEAD were assessed by ultrasonography. Results Patients with LEAD had significantly higher serum GDF15 levels than those without LEAD, regardless of whether their BMI was < 25 kg/m2 or ≥ 25 kg/m2 (both P < 0.05). Serum GDF15 levels were independently positively related to the F-IMT (standardized β = 0.162, P = 0.002). After adjusting for confounding factors, per 1-standard deviation (SD) increase in the serum GDF15 levels was significantly related to an approximately 1.4-fold increased risk of LEAD in the total population (P < 0.05). Regardless of whether the BMI was < 25 kg/m2 or ≥ 25 kg/m2, this association remained significant, with approximately 1.6- and 1.4-fold increased risks of LEAD, respectively (both P < 0.05). Conclusions High serum GDF15 levels were significantly correlated with an increased risk of LEAD in T2DM patients, and this relationship was independent of BMI.