The chemokine CCL1 triggers an AMFR-SPRY1 pathway that promotes differentiation of lung fibroblasts into myofibroblasts and drives pulmonary fibrosis.

Recruitment of immune cells to the site of inflammation by the chemokine CCL1 is important in the pathology of inflammatory diseases. Here, we examined the role of CCL1 in pulmonary fibrosis (PF). Bronchoalveolar lavage fluid from PF mouse models contained high amounts of CCL1, as did lung biopsies from PF patients. Immunofluorescence analyses revealed that alveolar macrophages and CD4+ T cells were major producers of CCL1 and targeted deletion of Ccl1 in these cells blunted pathology. Deletion of the CCL1 receptor Ccr8 in fibroblasts limited migration, but not activation, in response to CCL1. Mass spectrometry analyses of CCL1 complexes identified AMFR as a CCL1 receptor, and deletion of Amfr impaired fibroblast activation. Mechanistically, CCL1 binding triggered ubiquitination of the ERK inhibitor Spry1 by AMFR, thus activating Ras-mediated profibrotic protein synthesis. Antibody blockade of CCL1 ameliorated PF pathology, supporting the therapeutic potential of targeting this pathway for treating fibroproliferative lung diseases.

Body mass index and C-peptide are important for the promptly differential diagnosis of maturity-onset diabetes from familial type 2 diabetes in outpatient clinic.

Type 2 diabetic patients are becoming younger and having a tendency to family aggregation, they are easily suspected as maturity-onset diabetes of young (MODY) in the outpatient clinic and send to genetic testing. 9 diabetic families were compared in our outpatient clinic who met the primary diagnosis criteria of MODY. Detailed clinical features and laboratory data including gene sequence were collected and analyzed. The patients met the primary clinical diagnostic criteria of MODY for genetic testing at the first look. However, members of families A1 to A3 had normal Body mass index (BMI) and a lower C-peptide level which indicated impaired pancreatic islet function. In contrast, the members with diabetes of families B1 to B6 had normal or increased C-peptide level which indicated insulin resistance and were overweight with BMI. Genetic testing showed that the mutations in HNF1A, INS, KCNJ11 and so on in families A were consistent with the diagnosis of MODY. No pathogenic mutation was found in the members of families B which were diagnosed with familial T2D. Before the clinical laboratory testing and the further gene test, BMI and the concentration of C-peptide are important for the promptly differential diagnosis of MODY from familial type 2 diabetes and medication instruction in the outpatient clinic which could help to alleviate the burden of genetic testing for them.

Changes of Regulatory T Cells in the Early Stage of Obesity Mice and Their Modulation on Macrophage Subtypes in Visceral Adipose Tissue.

Objective To investigate the changes of regulatory T cells (Tregs) and whether Tregs can modulate the distribution of macrophage subtypes in visceral adipose tissue in the early stage of obesity.Methods After C57BL/6 mice obesity models were successfully established,metabolic parameters and numbers of Tregs and M1/M2 macrophage were measured at 4,10,and 20 weeks.The changes of metabolic parameters and adipose tissue inflammation in obesity mice after rapamycin intervention were evaluated. Results The early-stage obesity models were successfully established.Compared with normal diet mice,high fat diet mice had significantly higher epididymal adipose tissue mass and serum leptin levels(P<0.05).However,there was no statistical difference in blood glucose and insulin levels between these two groups(All P>0.05). Macrophages infiltration in adipose tissue in high fat diet mice gradually increased with time,coincident with decrease in Treg numbers. Increased numbers of Treg,improved metabolic parameters,and decreased ratio of M1/M2 can be seen after rapamycin intervention in mice.Conclusion The decrease of Tregs in the early stage of obesity may contribute to abnormal distribution of macrophage subtypes in visceral adipose.

Diabetes self-management, depressive symptoms, metabolic control and satisfaction with quality of life over time in Chinese youth with type 1 diabetes.

AIMS AND OBJECTIVES: To describe the patterns of diabetes self-management, depressive symptoms, metabolic control and satisfaction with quality of life over time in a cohort of Chinese youth with type 1 diabetes and to determine the relationships between these variables over time. BACKGROUND: Nurses have an important role in facilitating optimal self-management and health outcomes in youth with type 1 diabetes. Only a few studies have focused on patterns of diabetes adaptation over time in youth with type 1 diabetes, especially in China. Understanding changes in diabetes self-management, depressive symptoms, metabolic control and satisfaction with quality of life can facilitate assessment and intervention. DESIGN: This is a multi-site longitudinal descriptive study. Data for this report were collected at baseline with 136 eligible Chinese youth and 86 of them were followed up for the second time, 6-12 months after baseline data collection. METHODS: Instruments to measure diabetes self-management, depressive symptoms, metabolic control and satisfaction with quality of life were collected at two time points. The data were collected from July 2009-October 2010. Linear mixed model analysis was used to analyse the longitudinal data. RESULTS: Self-management decreased over time; however, depressive symptoms, metabolic control and satisfaction with quality of life did not change from baseline to 6-12 months in this sample of Chinese youth with type 1 diabetes. A decrease in diabetes self-management over time was associated with worse metabolic control, while an increase in depressive symptoms over time was associated with poorer quality of life satisfaction in this sample. CONCLUSIONS: Chinese youth faced difficulties with diabetes adaptation, especially with the deterioration of diabetes self-management. Improving self-management and decreasing depressive symptoms may enhance diabetes adaptation with respect to metabolic control and quality of life. RELEVANCE TO CLINICAL PRACTICE: The deterioration of diabetes self-management over time in youth with type 1 diabetes in China deserves nurses' careful surveillance. Clinical interventions appropriate to the Chinese culture and health care system are needed to improve self-management and depressive symptoms in Chinese youth with type 1 diabetes.

[Changes in fasting serum cortisol levels in adolescents with type 1 diabetes and elevated depressive symptoms].

OBJECTIVE: To study the changes in serum cortisol levels in adolescents with type 1 diabetes (T1DM) and elevated depressive symptoms. METHODS: Twenty-eight adolescents with T1DM and 31 healthy peers were assessed for depressive symptoms using a depression self-rating scale developed by the Epidemiological Survey Center. Selected subjects were classified into four groups: T1DM with elevated depressive symptoms group (n=15), T1DM without elevated depressive symptoms group (n=13), elevated depressive symptoms without T1DM group (n=15), and normal control group (n=16). Fasting blood samples were collected in the morning, and the levels of serum cortisol were compared among the four groups. The correlations of serum levels of cortisol and glycosylated hemoglobin A1c (HbA1c) with the score of depression self-rating scale were evaluated by Pearson correlation analysis. RESULTS: The fasting serum cortisol levels in the 28 T1DM patients were significantly higher than in the 31 healthy peers (P<0.01). The fasting cortisol levels in the T1DM with elevated depressive symptoms group were significantly higher compared with those in the elevated depressive symptoms without T1DM group and normal control group (P<0.01). In adolescents with T1DM, serum HbA1c level was positively correlated with the score of depression self-rating scale (r=0.481, P=0.010). CONCLUSIONS: The fasting serum cortisol levels in adolescents with T1DM and elevated depressive symptoms are significantly increased, suggesting that the patients with comorbidity of T1DM and depression develop dysfunction of the corticotropin-releasing hormone-adrenocorticotropic hormone-cortisol axis. The elevated depressive symptoms may be associated with a poor control of glucose metabolism.

Effectiveness of different waist circumference cut-off values in predicting metabolic syndrome prevalence and risk factors in adults in China.

OBJECTIVE: To study the effectiveness of waist circumference cut-off values in predicting the prevalence of metabolic syndrome (MetS) and risk factors in adults in China. METHODS: A cross-sectional survey was condcuted in 14 provinces (autonomous region, municipality) in China. A total of 47,325 adults aged⋝20 years were selected by multistage stratified sampling, and questionnaire survey and physical and clinical examination were conducted among them. MetS was defined according to the International Diabetes Federation (IDF) criteria and modified IDF criteria. RESULTS: The age-standardized prevalence of MetS was 24.2% (22.1% in men and 25.8% in women) and 19.5% (22.1% in men and 18.0% in women) according to the IDF criteria and modified IDF criteria respectively. The age-standardized prevalence of pre-MetS was 8.1% (8.6% in men and 7.8% in women) according to the modified IDF criteria. The prevalence of MetS was higher in urban residents than rural residents and in northern China residents than in southern China residents. The prevalence of central obesity was about 30% in both men and women according to the ethnicity-specific cut-off values of waist circumference for central obesity (90 cm for men and 85 cm for women). Multivariate regression analysis revealed no significant difference in risk factors between the two MetS definitions. CONCLUSION: Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China. Conclusion Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China.

Effect of high-fat or high-glucose diet on obesity and visceral adipose tissue in mice.

OBJECTIVE: To investigate the effect of high-fat or high-glucose diet on obesity and visceral adipose tissue in C57BL/6 mice. METHODS: Four-week-old C57BL/6 mice were allocated into normal diet group,high-fat diet group,and high-glucose diet group according to the random number table until 20 weeks old. Body weight,epididymal adipose tissue weight,blood leptin,fat infiltration in liver,M1/M2 macrophage subtypes,and monocyte chemoattractant protein-1 mRNA in epididymal adipose tissues were measured. RESULTS: Compared with normal diet group,body weight,epididymal adipose tissue weight,and leptin concentration in high fat diet group at 20 weeks were significantly increased (P < 0.05),and oil red O staining showed more prominent adipocyte infiltration in liver in high-fat diet group than those in normal diet and high-glucose diet group. However,no apparent differences were seen in high-glucose diet group at 20 weeks in terms of body weight,epididymal adipose tissue weight and leptin concentration. In high-fat diet group,the macrophages infiltration in epididymal adipose tissue increased with time and the percentage of M2 macrophage decreased in high-fat diet group than that in high-glucose diet group(P<0.05). Compared with normal diet group,monocyte chemoattractant protein-1 mRNA expression increased significantly in high-fat diet group(P<0.05). In high-glucose group,however,no significant differences were discerned (P > 0.05). CONCLUSION: High-fat diet,rather than 60% high glucose diet,will lead to obesity and macrophage infiltration in adipose tissues.

Chinese Expert Consensus on the Clinical Diagnosis and Management of Statin Intolerance.

The clinical benefits of statins have well-established and recognized worldwide. Although statins are well-tolerated generally, however, the report of statin-related adverse event and statin intolerance are common in China, which results in insufficient use of statins and poor adherence. The main reason may be attributed to confusions or misconceptions in the clinical diagnosis and management in China, including the lack of unified definitions and diagnostic standards, broad grasp of diagnosis, and unscientific management strategies. Based on that, this consensus carefully summarized the statin-related gene polymorphism and statin usage issue among Chinese population, and comprehensively reviewed global research data on statin intolerance, referenced guidelines, and consensus literature on statin intolerance in foreign and different regions, proposes an appropriate and easy to implement statin intolerance definition as well as corresponding diagnostic criteria and management strategies for Chinese clinicians, in order to improve the clinical application of statin drugs and enhance the prevention and treatment level of atherosclerotic cardiovascular disease in China.

Glycemic control among patients in China with type 2 diabetes mellitus receiving oral drugs or injectables.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly among Chinese adults, and limited data are available on T2DM management and the status of glycemic control in China. We assessed the efficacy of oral antidiabetes drugs (OADs), glucagon-like peptide-1 (GLP-1) receptor agonists, and insulin for treatment of T2DM across multiple regions in China. METHODS: This was a multicenter, cross-sectional survey of outpatients conducted in 606 hospitals across China. Data from all the patients were collected between April and June, 2011. RESULTS: A total of 238,639 patients were included in the survey. Eligible patients were treated with either OADs alone (n=157,212 [65.88%]), OADs plus insulin (n=80,973 [33.93%]), or OADs plus GLP-1 receptor agonists (n=454 [0.19%]). The OAD monotherapy, OAD + insulin, and OAD + GLP-1 receptor agonist groups had mean glycosylated hemoglobin (HbA1c) levels (±SD) of 7.67% (±1.58%), 8.21% (±1.91%), and 7.80% (±1.76%), respectively. Among those three groups, 34.63%, 26.21%, and 36.12% met the goal of HbA1c <7.0%, respectively. Mean HbA1c and achievement of A1c <7.0% was related to the duration of T2DM. CONCLUSIONS: Less than one third of the patients had achieved the goal of HbA1c <7.0%. Glycemic control decreased and insulin use increased with the duration of diabetes.

Diabetes self-management, depressive symptoms, quality of life and metabolic control in youth with type 1 diabetes in China.

AIMS AND OBJECTIVES: To assess diabetes self-management, depressive symptoms, quality of life and metabolic control in a cohort of youth with type 1 diabetes in mainland China. Predictors of self-management and depressive symptoms were also explored. BACKGROUND: Studies have shown that adaptation to childhood chronic illness is important in determining outcomes. Few studies have been reported on the behavioural, psychosocial and physiological adaptation processes and outcomes in Chinese youth with type 1 diabetes. DESIGN: This is a cross-sectional study as part of a multi-site longitudinal descriptive study. Data for this report were collected at baseline. METHODS: A convenience sample of 136 eligible youth was recruited during follow-up visits in hospitals in 14 major cities of Hunan Province (located in central southern mainland China) from July 2009-October 2010. Data were collected on socio-demographic background, clinical characteristics, diabetes self-management, depressive symptoms, quality of life and metabolic control. RESULTS: Diabetes self-management was lower in Chinese youth compared with a US cohort and was associated with insulin treatment regimen, treatment location, depressive symptoms and gender. A total of 17·6% of youth reported high depressive symptoms, and depressive symptoms were correlated with family annual revenue, school attendance, peer relationship and parent-child relationship. The mean score of global satisfaction with quality of life was 17·14 ± 3·58. The mean HbA1c was 9·68%. CONCLUSIONS: Living with type 1 diabetes poses considerable challenges, and Chinese youth report lower self-management than US youth and high depressive symptoms. Metabolic control and quality of life were sub-optimal. RELEVANCE TO CLINICAL PRACTICE: More clinic visits, treatment for high depressive symptoms and an intensive insulin regimen may improve diabetes self-management for youth with type 1 diabetes in China. Culturally appropriate interventions aimed at helping them adapt to living with the disease and improving outcomes are urgently needed.

[The safety and effectiveness of once daily detemir in patients with type 2 diabetes previously failing oral agents: the Chinese cohort from SOLVE(TM) observational study].

OBJECTIVE: Study of Once-daily LeVEmir(®) (SOLVE(TM)) was a 24-week international observational study to evaluate the safety and effectiveness of initiating once-daily insulin detemir (Levemir) as add-on therapy in patients with type 2 diabetes mellitus (T2DM) who failed treatment of oral anti-diabetic drugs (OAD). METHODS: The present study was derived from the data of Chinese cohort. A total of 3272 patients with T2DM failing OAD were enrolled in the study. Determir were prescribed to the patients by the decision of the physician. Clinical data were collected at baseline, week 12 and week 24 to evaluate the safety and effectiveness of detemir. RESULTS: The age of the patients was (56.2 ± 10.8) years with a diabetes duration of (7.1 ± 5.2) years. Their BMI was (25.3 ± 3.3) kg/m(2). No patient experienced any major or nocturnal hypoglycaemic event during the study. After 24 weeks of treatment, the glycosylated hemoglobin A1c (HbA1c) decreased from (8.33 ± 1.69)% to (7.16 ± 1.18)% with a mean change of -1.17%, the fasting plasma glucose decreased from (9.52 ± 2.59) mmol/L to (6.84 ± 1.42) mmol/L with a mean change of -2.7 mmol/L, and the 7-point blood glucose profile improved overall. Totally 49.1% of patients achieved HbA1c < 7%. The mean body weight decreased by 0.15 kg. CONCLUSIONS: Insulin detemir administered once daily as add-on therapy in patients with T2DM failing OAD regimen significantly reduces the risk of major hypoglycemia, improves glycemic control, increases the percentage of patients achieving treatment target with neutral effect on body weight.

[Relationship between body fat distribution and insulin resistance, islet ß cell function and metabolic disorders in adults].

OBJECTIVE: To explore the relationship between body fat distribution, insulin resistance, islet ß cell function and metabolic disorders in adult population. METHODS: From February to November 2012, a total of 174 subjects aged 20-68 years were recruited. Their anthropometric parameters, blood biochemical indices and the results of oral glucose tolerance test (OGTT) and insulin releasing test (IRT) were collected. Body fat distribution was measured with dual energy X-ray absorptiometry (DEXA). RESULTS: The values of trunk/total fat mass (T/B) and android/gynoid fat mass ratio (A/G) were positively correlated with blood pressure, blood lipid, plasma glucose, insulin resistance index (HOMA-IR) and high-sensitivity C-reactive protein. Compared with the group of normal metabolism, the group of metabolic disorders had higher T/B and A/G (P < 0.05). After multiple stepwise regression analysis, the main influencing factors of lnHOMA-IR and lnHOMA-ß were T/B and Grespectively.Logistic regression showed that A (OR = 3.01, 95%CI 1.86-8.17) was a risk factor for diabetes and A/G (OR = 2.71, 95%CI 1.75-6.56) a risk factor for dyslipidemia. CONCLUSIONS: Trunk and android fat deposition aggravates insulin resistance, metabolic disorders. And the main influencing factors of insulin resistance and islet ß cell function are trunk and gynoid fat respectively. Android fat mass is a major risk factor for glycolipid metabolism.

PCDD/Fs, PBDD/Fs, and PBDEs in the air of an e-waste recycling area (Taizhou) in China: current levels, composition profiles, and potential cancer risks.

Atmospheric concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs), and polybrominated diphenyl ethers (PBDEs) were measured in Taizhou, a large electronic equipment waste (e-waste) recycling area in East China. The mean concentrations (in summer and winter) of PCDD/Fs (0.45 and 0.39 pg WHO-TEQ m⁻³, where WHO-TEQ is the toxic equivalent set by the World Health Organisation), PBDD/Fs (0.22 and 0.18 pg WHO-TEQ m⁻³), and PBDEs (270 and 225 pg m⁻³) in this region have declined compared with those in 2005, due to regulations on primitive e-waste recycling activities. However, these concentrations remain higher than the historically highest levels in Europe and North America. The congener profiles of 2,3,7,8-substituted PCDD/Fs were similar, with OCDD, 1,2,3,4,6,7,8-HpCDF, OCDF, and 1,2,3,4,6,7,8-HpCDD being the most abundant congeners at all sites. The PCDD/F homologue profiles in the present study were different from those typically observed at non-e-waste locations, indicating a distinct source in this region. Seasonal differences were found in the lower brominated PBDE profiles. These differences indicate that the PBDE emission sources in summer (e.g., strong evaporation sources) differed from those in winter. However, the relatively steady congener profiles of the highly brominated PBDEs suggest that these PBDEs were controlled primarily by similar emission mechanisms. The lifetime excess cancer risks from exposure to PCDD/Fs and PBDD/Fs via inhalation ranged from 0.7 × 10⁻5 to 5.4 × 10⁻5, or approximately 80 cancer cases in the Taizhou population.

[The baseline characteristics of patients with type 2 diabetes initiating insulin detemir : the Chinese cohort from the SOLVE(TM) study].

OBJECTIVE: To characterize the baseline status of Chinese diabetic patients based on data derived from Chinese cohort from SOLVE(TM) study. METHODS: Patients with type 2 diabetes initiating basal insulin detemir at the decision of the physician were eligible for the study. Data on demographics, medical history, glycemic profile and treatment regimen at baseline were collected by physicians. RESULTS: A total of 3272 patients [female 42%, male 58%, mean age (56.2 ± 10.8) years] were included in the study. Their BMI was (25.3 ± 3.3) kg/m(2). The duration of diabetes was 4.0 (0.1 - 27.0) years, and the duration of treatment with oral antidiabetic drugs (OADs) was 3.0 (0.0 - 20.2) years. The proportions of subjects with diabetic macro- and micro-vascular complications were 15.8% (515 cases) and 27.1% (866 cases), respectively. The hemoglobin A1c (HbA1c) at baseline was (8.33 ± 1.70)%, and the fasting blood glucose (FPG) was (9.5 ± 2.6) mmol/L. CONCLUSIONS: A large proportion of patients with type 2 diabetes remain in poor glycemic control, and the prevalence of diabetic complications is high, which requires optimal therapeutic strategy for the patients with suboptimal glycemic control.

[Protective effect of adipocytes fatty acid binding protein inhibitor on pancreas islet cell against macrophage-mediated cytotoxicity of mice in vitro].

OBJECTIVE: To investigate the potential role of adipocytes fatty acid binding protein (A-FABP)inhibitor to prevent pancreatic islet cells from cytotoxic injury by inflammatory cytokines released from macrophage. METHODS: Co-culture system for RAW264.7 macrophage and MIN6 insulinoma cells was established through transwell combined with A-FABP inhibitor BMS309403 treatment for 48 h. Meanwhile, cultured RAW264.7 and MIN6 respectively were set up as controls. In the inhibitor group, BMS309403 preprocessing (5 µmol/L) was performed 2 h before co-culture. The expression of toll-like receptors(TLR)4 and A-FABP in RAW264.7 macrophages was detected by RT-PCR and Western blotting, interleukin (IL)-1ß and tumor necrosis factor(TNF)-α levels in the supernatant were detected by ELISA, Glucose-stimulated insulin level was detected by insulin radioimmuno-assay kits for the function of islets. RESULTS: (1) The mRNA and protein levels of both TLR4 and A-FABP in RAW264.7 macrophages as well as the concentrations of IL-1ß and TNF-α in the supernatant were significantly higher in co-culture group than in macrophages control group (P < 0.05). (2) Insulin secretion stimulated by high glucose was obviously decreased in co-culture group when compared with insulinoma cells control group [(16.0 ± 2.2) vs (41.1 ± 6.6) ng/ml, P < 0.05]. After the treatment with A-FABP inhibitor, the mRNA and protein levels of both TLR4 and A-FABP as well as the concentrations of IL-1ß and TNF-α in the supernatant were significantly lower than in co-culture control (P < 0.05). However, insulin secretion stimulated by high glucose was significantly enhanced when compared with insulinoma cells control group [(31.4 ± 3.3) vs (16.0 ± 2.2) ng/ml, P < 0.05]. CONCLUSIONS: This study demonstrated that co-culture of macrophage and islet cells can activate inflammation pathway, stimulate inflammatory cytokine release and decrease insulin secretion from islet cells. A-FABP inhibitor can protect islet cells from macrophage-mediated cytotoxicity and preserve its insulin secretory function.

[1α, 25(OH)(2) D(3) protects pancreatic ß-cell line from cytokine-induced apoptosis and impaired insulin secretion].

OBJECTIVE: To explore the protective effects and potential mechanisms of 1α, 25(OH)(2) D(3) (VitD(3)) on pancreatic ß-cells. METHODS: The apoptosis of NIT-1 cells was induced by interleukin-1ß (IL-1ß) and interferon-γ (IFN-γ) in vitro. Then the apoptotic rate of NIT-1 cells was determined by Hoechest33342 staining and Annexin V-FITC/PI flow cytometry. The insulin secretion level of NIT-1 cells was measured by ELISA. The NIT-1 cells were treated with VitD(3) at the final concentrations of 10(-8) mol/L or underwent transient transfection with vitamin D receptor (VDR)-SiRNA. RESULTS: After the treatment of VitD(3), the apoptotic rate of NIT-1 cells decreased to 39.7%. There were significant differences in apoptotic rate between the VitD(3) treatment and IL-1ß/IFN-γ groups (68.4%) (P < 0.01). Similarly impaired glucose-stimulated insulin secretion (GSIS) of NIT-1 cells recovered ((7.34 ± 0.21) ng/ml) after the treatment of VitD(3) as compared with the IL-1ß/IFN-γ group ((4.88 ± 0.32) ng/ml, P < 0.01). Moreover, most of the protective effects of VitD(3) on pancreatic ß-cells could be blocked by the transfection of VDR-SiRNA. CONCLUSION: VitD(3) may protect pancreatic ß-cells from cytokine-induced apoptosis and impaired insulin secretion through its conjugation with VDR.

Role of omega-3 fatty acids in the prevention and treatment of cardiovascular Diseases: A consensus statement from the Experts' Committee Of National Society Of Cardiometabolic Medicine.

Low-density lipoprotein cholesterol (LDL-C) has been considered as the primary target for the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, there are still residual cardiovascular risks in some patients even if LDL-C achieves the target level. Emerging evidence suggestes that elevated triglyceride (TG) level or triglyceride-rich lipoprotein (TRL) cholesterol (TRL-C) is one of the important components of the residual cardiovascular risks. Omega-3 fatty acids have been shown to be one of the effective drugs for reducing TG. However, its efficacy in reducing the risk of ASCVD is inconsistent in large randomized clinical trials. There is lack of consensus among Experts regarding the application of omega-3 fatty acids in cardiovascular diseases including heart failure, arrhythmia, cardiomyopathy, hypertension, and sudden death. Hence, the current consensus will comprehensively and scientifically present the detailed knowledge about the omega-3 fatty acids from a variety of aspects to provide a reference for its management of omega-3 fatty acids application in the Chinese population.

[Histone H3 acetylation of tumor necrosis factor-alpha and cyclooxygenase-2 in patients with type 2 diabetes].

OBJECTIVE: To investigate the expression of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) mRNA and evaluate the status of histone H3 acetylation at TNF-α and COX-2 promoter in peripheral blood mononuclear cells (PBMCs) from type 2 diabetics. METHODS: The PBMCs from 12 type 2 diabetics and 12 healthy controls were isolated by Ficoll-Hypaque density gradient centrifugation. The differential expression of TNF-α and COX-2 mRNA was measured by real-time PCR (polymerase chain reaction). Chromatin immunoprecipitation analysis was used to detect the status of H3 acetylation at TNF-α and COX-2 promoter region. RESULTS: TNF-α and COX-2 mRNA were overexpressed in PBMCs from Type 2 diabetics as compared with normal controls (2.28 ± 0.09 fold and 2.78 ± 0.26 fold).(P < 0.05). Compared with normal controls, H3 acetylation at the TNF-α (1.54 ± 0.43 vs 0.97 ± 0.39, P = 0.0094) and COX-2 (1.20 ± 0.58 vs 0.64 ± 0.21, P = 0.0161) gene promoter region was elevated in PBMCs from Type 2 diabetic patients. CONCLUSION: Increased H3 acetylation at TNF-α and COX-2 promoter in PBMCs from type 2 diabetics may contribute to the pathogenesis of type 2 diabetes through the elevated expressions of TNF-α and COX-2.

Accurate diagnosis and heterogeneity analysis of a 17q12 deletion syndrome family with adulthood diabetes onset and complex clinical phenotypes.

PURPOSE: 17q12 Deletion Syndrome is heterogeneous and the reasons remain unclear. We clarified the clinical characteristics of adulthood diabetes onset 17q12 deletion syndrome and investigated the unclear phenotype-genotype correlation. METHODS: We collected the clinical history and laboratory results of a family with autosomal dominant inheritance diabetes and renopathy. Sanger sequencing of HNF1B and a panel of monogenic diabetic genes were performed to identify the monogenetic diabetes. Semiquantitative PCR and Chromosome 100 K sequence analysis were performed to analyze the copy numbers variation of diabetes related genes. Allelic specific quantitative PCR were used for TBC1D3 and paralogues diagnosis. The reported cases were reviewed and assessed to compare with patients in this study. RESULTS: Differential variants in genomic DNA and clinical presentations among family members were explored to determine the probable phenotype-genotypes correlation. The four patients were diagnosed with 17q12 deletion syndrome with 1.47-1.76 Mb heterogeneous deletion, which led to the haploinsufficiency of HNF1B, ACACA, LHX1, PIGW, miRNA2909 and other genes. The patients had different amount of genes deletion in TBC1D3 and paralogues, which might associate with the heterogeneous clinical phenotypes. CONCLUSIONS: We first reported an adulthood diabetes onset 17q12 deletion syndrome family with the largest number of patients. The heterogeneous clinical phenotypes might be related to the haploinsufficiency of TBC1D3 and its paralogues.