The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Type 1 diabetes mellitus (T1DM)-induced cognitive dysfunction is common, but its underlying mechanisms are still poorly understood. In this study, we found that knockout of conventional protein kinase C (cPKC)γ significantly increased the phosphorylation of Tau at Ser214 and neurofibrillary tangles, but did not affect the activities of GSK-3β and PP2A in the hippocampal neurons of T1DM mice. cPKCγ deficiency significantly decreased the level of autophagy in the hippocampal neurons of T1DM mice. Activation of autophagy greatly alleviated the cognitive impairment induced by cPKCγ deficiency in T1DM mice. Moreover, cPKCγ deficiency reduced the AMPK phosphorylation levels and increased the phosphorylation levels of mTOR in vivo and in vitro. The high glucose-induced Tau phosphorylation at Ser214 was further increased by the autophagy inhibitor and was significantly decreased by an mTOR inhibitor. In conclusion, these results indicated that cPKCγ promotes autophagy through the AMPK/mTOR signaling pathway, thus reducing the level of phosphorylated Tau at Ser214 and neurofibrillary tangles.
AMP-Activated Protein Kinases/metabolism* ; Animals ; Autophagy ; Diabetes Mellitus, Type 1 ; Glucose ; Glycogen Synthase Kinase 3 beta/metabolism* ; Mice ; Phosphorylation ; Protein Kinase C/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; tau Proteins/metabolism*

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

The 70 thannual scientific sessions of the American College of Cardiology(ACC) were held online at Atlanta, USA from May 15 th to 17 th, 2021, covering clinical practice, guideline recommendations, and clinical academic research(especially the late-breaking clinical trial presentation) related to cardiovascular disease(CVD). Diabetes mellitus, as CVD risk equivalent, and obesity are important risk factors for CVD, and fatty liver as a chronic metabolic disease has also been proved to be associated with CVD. This report reviews the research advance and academic perspectives on diabetes and other chronic metabolic diseases.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Objective:This was a retrospective study to compare the serum 25-hydroxy vitamin D [25(OH)D], retinol binding protein 4(RBP-4) and other clinical data in type 2 diabetes mellitus (T2DM) patients with or without diabetic nephropathy (DN) and to explore the clinical significance of these indicators in DN.Methods:1946 T2DM patients were enrolled in this study. The T2DM patients were divided to group with diabetic nephropathy (DN group) and without diabetic nephropathy (NDN group). According to the urine albumin to creatinine ratio (UACR), DN patients were further divided into microalbuminuria subgroup (UACR 30~300 mg/g) and massive proteinuria subgroup (UACR> /g). Clinical characteristics including serum 25(OH)D, RBP-4 and other biochemical indicators were collected.Results:Compared with NDN group, DN group showed longer disease duration, older age and higher levels of HbA1c, RBP-4, hs-CRP, TC and TG; 25(OH)D and HDL-C in DN group were lower than those in NDN group ( P<0.05). Within DN group, massive proteinuria subgroup showed higher RBP-4, younger age and lower 25(OH)D and HDL-C than microalbuminuria subgroup ( P<0.05). After adjusted for age, gender and disease duration in DN, partial correlation analysis showed that 25(OH)D is positively correlated with eGFR, and negatively correlated with RBP-4 and UACR ( P<0.05). UACR is positively correlated with RBP-4 and TC, and negatively correlated with eGFR (all P<0.05). eGFR is negatively correlated with RBP-4, TC and UACR (all P<0.05). Multivariate logistic regression showed that disease duration, HbA1c, RBP-4 and hs-CRP are risk factors for DN, and 25(OH)D is the protective factor for DN. Conclusions:Decreased 25(OH)D and increased RBP-4 are associated with increased DN risk in T2DM patients, and also associated with exacerbated albuminuria and deteriorated renal function in DN patients. There is a negative correlation between 25(OH)D and RBP-4 in DN. Therefore, it is necessary to strengthen the monitoring of serum 25(OH)D and RBP-4 and enhance vitamin D supplementation in T2DM patients to prevent the occurrence and delay the progression of diabetic nephropathy.

Adriamycin resistance in HCC seriously hinders the treatment of patients, it is necessary to investigate the mechanisms. Autophagy is involved in adriamycin resistance and JNK2 is related to autophagy. However, whether JNK2 inducing drug resistance though autophagy is unknown. GL-V9, a new synthesized flavonoid derivative, has been proved of its anti-tumor effects. The aim of the study is to explore the role of JNK2-related autophagy on adriamycin-induced drug resistance and the effects of GL-V9 on reversing adriamycin resistance. We concluded that JNK2 played an important role in drug resistance induced by adriamycin. The high expression of JNK2 activated protective autophagy in Hep G2-DOXR cells under non-stress condition, which protected cells from drug attacking. Furthermore, we found that GL-V9 reversed adriamycin resistance by blocking the JNK2-related protective autophagy in HCC.

Objective To investigate the relevant factors of type 2 diabetes mellitus (T2DM) with cerebral infarction (CI).Methods A total of 323 patients with T2DM from February 2012 to March 2017 in Inner Mongolia medical university affiliated hospital were included in this study.150 patients with T2DM and CI were considered as experiment group,173 cases of T2DM without CI were considered as control group.The clinical data of two groups were analyzed.Results The history of diabetes,smoking and hypertension were longer in experiment group than in control group (P＜ 0.05).The patients in experiment group had higher fasting blood glucose (FBG),glycosylated hemoglobin (HbA1c),total triglycerides (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),non-HDL-C,homocysteine (Hcy),fibrinogen (FIB),retinol binding protein 4 (RBP4) and lower HDL-C,apolipoprotein A1 (ApoA1) than the patients in control group (P＜ 0.05).Multiple-factor logistic regression analysis showed that long-term smoking,long history of hypertension,high TG,high LDL-C,high non-HDL-C,high Hcy,high RBP4,low HDL-C and low ApoA1 were risk factors for CI in patients with T2DM (P＜0.05).After adjusting common variables (diabetes history,hypertension history,smoking history,HbA1c,TG,TC),multiple-factor logistic regression analysis showed that LDL-C,non-HDL-C,Hcy,RBP4 were risk factors for CI in T2DM (P＜0.05).HDL-C and ApoA1 were protective factors for CI in T2DM (P＜0.05).Conclusion The risk factors for CI in patients with T2DM include long-term smoking,long hypertension history,high HbA1c,high TG,high LDL-C,high non-HDL-C,high Hcy,high RBP4,low HDL-C and low ApoA1.Patients should be advised to quit smoking,control blood glucose and blood pressure,and regulate blood lipid levels.

Objective To investigate the potential effects of simvastatin on angiotensin Ⅱ-stimulated secretion and proliferation of adrenocortical carcinoma H295R cells.Methods The H295R cells were divided into control group, Angiotensin Ⅱgroup, simvastatin group and Angiotensin Ⅱ plus simvastatin group.Cortisol in medium was determined by chemiluminescent method , and aldosterone was determined by radioimmunoassay .The mRNA expression of 11 beta-hydroxylase ( CYP11B1 ) and aldosterone synthase ( CYP11B2 ) were examined by RT-qPCR.Cell proliferation was detected by MTS method.Results Compared with control group, angiotensin Ⅱincreased the secretion of cortisol and aldosterone, and the expression of CYP11B1 and CYP11B2.Simvastatin decreased cortisol secretion and CYP11B1 mRNA expression ( P<0.05 ) .Simvastatin also inhibited angiotensinⅡ-induced the secretion of cortisol and aldosterone , and the expression of CYP 11 B1 and CYP11 B2 compared with Angiotensin Ⅱgroup ( P<0.05 ) .Angiotensin Ⅱhad no effect on cell proliferation , while simvastatin significantly inhibited cell proliferation .The inhibitory effect of simvastatin on proliferation was enhanced when simvastatin was prescribed with angiotensin Ⅱ( P<0.05 ) .Conclusions Simvastatin inhibits angiotensin Ⅱ-induced secretion of cortisol and aldosterone in H295R cells.Simvastatin inhibits cell proliferation, which could be enhanced by angio-tensin Ⅱ.

BACKGROUNDNon-small cell lung cancer (NSCLC) is one of the most common malignant tumors. Despite the advances in therapy over the years, its mortality remains high. The aim of this study was to evaluate the expression of small ubiquitin-like modifier (SUMO) proteases 1 (SENP1) in NSCLC tissues and its role in the regulation of vascular endothelial growth factor (VEGF) expression. We also investigated the association between the expression level of SENP1 and the clinicopathological features and survival of the patients.

METHODSA SENP1 small interfering RNA (siRNA) was constructed and transfected into the NSCLC cells. VEGF gene expression was analyzed by real-time polymerase chain reaction (RT-PCR). Immunohistochemistry staining was used to assess the expression of SENP1 in 100 NSCLC patients and its association with the clinicopathological features and survival was analyzed.

RESULTSVEGF expression was significantly higher in NSCLC tissues than in normal lung tissues. Inhibition of SENP1 by siRNA was associated with decreased VEGF expression. SENP1 was over-expressed in 55 of the 100 NSCLC samples (55%) and was associated with a moderate and low histological tumor grade (3.6%, 38.2%, and 58.2% in high, moderate and low differentiated tumors, respectively, P = 0.046), higher T stage (10.9% in T1, and 89.1% in T2 and T3 tumor samples, P < 0.001) and TNM stage (10.9% in stage I, and 89.1% in stages II and III tumor samples, P < 0.001). The rate of lymph node metastasis was significantly higher in the SENP1 over-expression group (76.4%) than that in the SENP1 low expression group (33.3%, P < 0.001). Sixty three patients received postoperative chemotherapy, including 34 with SENP1 over-expression and 29 with SENP1 low expression. Among the 34 patients with SENP1 over-expression, 22 (64.7%) patients developed recurrence or metastasis, significantly higher than those in the low expression group 27.6% (8/29) (P = 0.005). Multivariate Cox regression analysis showed that lymph node metastasis (P = 0.015), TNM stage (P = 0.001), and SENP1 expression level (P = 0.002) were independent prognostic factors for the survival of NSCLC patients.

CONCLUSIONSSENP1 may be a promising predictor of survival, a predictive factor of chemo-sensitivity for NSCLC patients, and potentially a desirable drug target for lung carcinoma target therapy.

Antineoplastic Agents ; therapeutic use ; Blotting, Western ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; metabolism ; Cell Line, Tumor ; Cysteine Endopeptidases ; Endopeptidases ; genetics ; metabolism ; Female ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; Male ; Reverse Transcriptase Polymerase Chain Reaction