Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation.

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

Berberine improves intralipid-induced insulin resistance in murine.

Insulin resistance (IR) is a major metabolic risk factor even before the onset of hyperglycemia. Recently, berberine (BBR) is found to improve hyperglycemia and IR. In this study, we investigated whether BBR could improve IR independent of hyperglycemia. Acute insulin-resistant state was induced in rats by systemic infusion of intralipid (6.6%). BBR was administered via different delivery routes before or after the beginning of a 2-h euglycemic-hyperinsulinemic clamp. At the end of experiment, rats were sacrificed, gastrocnemius muscle was collected for detecting mitochondrial swelling, phosphorylation of Akt and AMPK, as well as the mitochondrial permeability regulator cyclophilin D (CypD) protein expression. We showed that BBR administration markedly ameliorated intralipid-induced IR without affecting blood glucose, which was accompanied by alleviated mitochondrial swelling in skeletal muscle. We used human skeletal muscle cells (HSMCs), AML12 hepatocytes, human umbilical vein endothelial cells, and CypD knockout mice to investigate metabolic and molecular alternations. In either HSMCs or AML12 hepatocytes, BBR (5 µM) abolished palmitate acid (PA)-induced increase of CypD protein levels. In CypD-deficient mice, intralipid-induced IR was greatly attenuated and the beneficial effect of BBR was diminished. Furthermore, we demonstrated that the inhibitory effect of BBR on intralipid-induced IR was mainly mediated by skeletal muscle, but not by intestine, liver, or microvasculature; BBR administration suppressed intralipid-induced upregulation of CypD expression in skeletal muscle. These results suggest that BBR alleviates intralipid-induced IR, which is related to the inhibition of CypD protein expression in skeletal muscle.

FSH signaling is involved in affective disorders.

Affective disorders are a set of mental disorders and particularly disrupt the mental health of susceptible women during puberty, pregnancy, parturition and menopause transition, which are characterized by dramatic changes in reproductive hormone profiles. The serum FSH level changes significantly during these periods; yet, the role of FSH in mood regulation is poorly understood. In the current study, FSHR knockout (Fshr-/-) mice displayed enhanced affective disorder behaviors in an open field test and a forced swim test, accompanied by altered gene expression profiles. The differentially expressed genes between Fshr-/- mice and Fshr+/+ mice were enriched in multiple neuroendocrine metabolic pathways. FSHR deletion significantly increased/decreased the mRNA and/or protein expression levels of AOX1, RDH12, HTR3a and HTR4 in mood-mediating brain regions, including the hippocampus and prefrontal cortex. These results reveal that FSH signaling is involved in the development of affective disorders.

FSHR ablation induces depression-like behaviors.

Alteration in reproductive hormones profile is associated with the increasing risk of menopausal depression in women. Serum follicle-stimulating hormone (FSH) level is changed during the menopause transition, while the effect of FSH on menopausal depression has remained undefined. In this study we investigated whether or how FSH affected menopausal depression in postmenopausal (ovariectomized) FSHR knockout mice (Fshr-/-). We found that Fshr-/- mice displayed aggravated depression-like behaviors, accompanied by severe oxidative stress in the whole brain, resulted from significantly reduced glutamate cysteine ligase modifier subunit (GCLm) in glutathione synthesis and glucose-6-phosphate dehydrogenase (G6PD) in NADP/NADPH transition. Importantly, administration of ROS scavenger N-acetyl cysteine (NAC, 150 mg · kg-1 · d-1, i.p. for 12 weeks) attenuated the depression-like behaviors of Fshr-/- mice. Consistent with these in vivo experiment results, we found that pretreatment with FSH (50, 100 ng/mL) dose-dependently increased protein levels of GCLm and G6PD, and decreased the ROS production in N2a mouse neuroblastoma cells. These findings demonstrate that FSH signaling is involved in pathogenesis of menopausal depression, and likely to maintain the redox-optimized ROS balance in neurons.

Thyroxine therapy ameliorates serum levels of eicosanoids in Chinese subclinical hypothyroidism patients.

AIM: The eicosanoids derived from phospholipids play key roles in inflammation. However, the profiles of serum eicosanoids in subclinical hypothyroidism (SH) patients and the effects of thyroxine replacement therapy (TRT) on these eicosanoids remain unclear. Many studies show that TSH regulates lipid metabolism. As eicosanoids derived from phospholipids play key roles in oxidative stress and immune function and inflammatory process, it was necessary to explore the profiles of serum eicosanoids in SH patients and the effects of thyroxine replacement therapy (TRT) on the eicosanoids. METHODS: A total of 50 Chinese SH patients and 22 healthy volunteers were recruited. SH patients received TRT (L-T4, 25 and 50 mcg/d for patients with TSH≤10.0 mIU/L and TSH>10.0 mIU/L, respectively) for 3 months. Serum levels of major eicosanoids and cPLA2 were analyzed using LC-MS and clinical biochemical assays. RESULTS: The serum levels of cPLA2, eicosanoids (8-isoPGF2a, 11-dehydroTXB2 and 12-HETE) and 11-dehydroTXB2/6-Keto-PGF1a were significantly elevated in SH patients. The serum TSH levels were significantly correlated with the levels of cPLA2 (r=+0.65), 11-dehydroTXB2 (r=+0.32) and 11-dehydroTXB2/6-Keto-PGF1a (r=+0.37). After 3-month TRT, the serum levels of TSH, cPLA2 and the above-mentioned eicosanoids in SH patients were significantly decreased. CONCLUSION: The metabolism of eicosanoids is significantly altered in Chinese SH patients, and TRT can ameliorate the abnormalities of serum eicosanoid levels.

KILLER CELL IMMUNOGLOBULIN-LIKE RECEPTOR GENES AND THEIR HLA-C LIGANDS IN HASHIMOTO THYROIDITIS IN A CHINESE POPULATION.

OBJECTIVE: Natural killer (NK) cells serve as primary immune surveillance and are partially regulated by combinations of killer immunoglobulin-like receptors (KIR) and their human leukocyte antigen-C (HLA-C) ligands. Alterations in NK cell activity have been associated with Hashimoto thyroiditis (HT). The aim of this study was to determine whether certain KIR/HLA-C genotype combinations play a role in HT pathogenesis. METHODS: The present study enrolled 107 unrelated HT patients and 108 random healthy individuals in a case-control study. Blood was collected for DNA extraction; typing of KIR genes and HLA-C alleles was performed by polymerase chain reaction with sequence specific primers (PCR-SSP), followed by electrophoresis on agarose gels. RESULTS: Among a panel of KIR2D/HLA-C genotype combinations, the frequency of KIR2DS2/HLA-C1 was significantly increased in HT patients compared to controls (33.64% vs. 12.96%, P<.001). To further analyze the precise genotype, we investigated inhibitory or activating KIR/HLA-C gene pairs when their corresponding activating or inhibitory KIR genes were absent in the 2 groups. Only the frequency of KIR2DS2(-)2DL2/3(+)HLA-C1(+) was significantly decreased in HT patients compared to controls (48.60% vs. 70.37%, P = .001). CONCLUSION: Our data suggest that KIR2DS2/HLA-C1 may correlate with HT pathogenesis. On the contrary, the predominance of KIR2DL2/3/HLA-C1 in the absence of KIR2DS2 suggests a potential inhibitory role in HT pathogenesis. In conclusion, our findings may further elucidate the mechanisms underlying the pathogenesis of HT and other autoimmune diseases. ABBREVIATIONS: HLA-C = human leukocyte antigen-C HT = Hashimoto thyroiditis KIR = killer immunoglobulin-like receptor NK = natural killer PCR = polymerase chain reaction.

Robust evidence for five new Graves' disease risk loci from a staged genome-wide association analysis.

Graves' disease (GD), characterized by autoantibodies targeting antigens specifically expressed in thyroid tissues causing hyperthyroidism, is triggered by a combination of genetic and environmental factors. However, only a few loci for GD risk were confirmed in the various ethnic groups, and additional genetic determinants have to be detected. In this study, we carried out a three-stage study in 9529 patients with GD and 9984 controls to identify new risk loci for GD and found genome-wide significant associations in the overall populations for five novel susceptibility loci: the GPR174-ITM2A at Xq21.1, C1QTNF6-RAC2 at 22q12.3-13.1, SLAMF6 at 1q23.2, ABO at 9q34.2 and an intergenic region harboring two non-coding RNAs at 14q32.2 and one previous indefinite locus, TG at 8q24.22 (Pcombined < 5 × 10(-8)). The genotypes of corresponding variants at 14q32.2 and 8q24.22 were correlated with the expression levels of C14orf64 and a TG transcript skipping exon 46, respectively. This study increased the number of GD loci with compelling evidence and indicated that non-coding RNAs might be potentially involved in the pathogenesis of GD.

Prognostic significance of cyclooxygenase-2 protein in pancreatic cancer: a meta-analysis.

We conducted a meta-analysis of relevant cohort studies to investigate the relationships between cyclooxygenase-2 (COX-2) protein and the prognosis of pancreatic cancer. The following electronic databases were searched without language restrictions: MEDLINE (1966∼2013), the Library Database (Issue 12, 2013), EMBASE (1980∼2013), CINAHL (1982∼2013), Web of Science (1945∼2013), and the Chinese Biomedical Database (CBM) (1982∼2013). Meta-analysis was performed using the STATA statistical software. Six cohort studies with a total of 712 pancreatic cancer patients were involved in this meta-analysis. Our findings showed that COX-2-positive patients were significantly associated with a shorter overall survival (OS) than COX-2-negative patients (hazard ratio (HR) = 1.48, 95 % confidence interval (95%CI) = 1.12∼1.85, P < 0.001). A subgroup analysis by ethnicity also revealed that pancreatic cancer patients with an abnormal COX-2 expression exhibited a worse OS than COX-2-negative patients among both Asians and Caucasians (Asians: HR = 1.40, 95%CI = -0.09∼2.89, P = 0.066; Caucasians: HR = 1.49, 95%CI = 1.11∼1.87, P < 0.001, respectively). Our findings provide empirical evidence that abnormal COX-2 expression may be strongly correlated with poor prognosis for patients with pancreatic cancer. Thus, COX-2 protein may be a useful biomarker for pancreatic cancer.

Abnormal MGMT promoter methylation may contribute to the risk of esophageal cancer: a meta-analysis of cohort studies.

This meta-analysis was conducted aiming to evaluate the relationship between abnormal O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and the risk of esophageal cancer (EC). A range of electronic databases was searched: Web of Science (1945 ~ 2013), the Cochrane Library Database (Issue 12, 2013), MEDLINE (1966 ~ 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013) without language restrictions. Meta-analysis was performed with the use of the STATA 12.0 software. In the present meta-analysis, 9 clinical cohort studies with a total of 861 EC patients were included. The pooled results revealed that the frequency of MGMT promoter methylation in cancer tissues was significantly higher than in adjacent and normal tissues (cancer tissues vs adjacent tissues, odds ratio (OR) = 6.73, 95 % confidence intervals (95 % CI) 4.75 ~ 9.55, P < 0.001; cancer tissues vs normal tissues, OR = 13.68, 95 % CI 9.47 ~ 19.75, P < 0.001, respectively). Subgroup analyses by pathological type, ethnicity, and sample size suggested that abnormal MGMT promoter methylation also exhibited a higher frequency in all these subgroups (all P < 0.05). Our findings provide empirical evidence that abnormal MGMT promoter methylation may contribute to the risk of EC. Thus, detection of MGMT promoter methylation may be utilized as a valuable diagnostic marker for EC.

Alpha-lipoic acid attenuates insulin resistance and improves glucose metabolism in high fat diet-fed mice.

AIM: To investigate whether alpha-lipoic acid (ALA) could attenuate the insulin resistance and metabolic disorders in high fat diet-fed mice. METHODS: Male mice were fed a high fat diet (HFD) plus ALA (100 and 200 mg·kg(-1)·d(-1)) or HFD plus a positive control drug metformin (300 mg·kg(-1)·d(-1)) for 24 weeks. During the treatments, the relevant physiological and metabolic parameters of the mice were measured. After the mice were euthanized, blood samples and livers were collected. The expression of proteins and genes related to glucose metabolism in livers were analyzed by immunoblotting and real time-PCR. RESULTS: HFD induced non-alcoholic fatty liver disease (NAFLD) and abnormal physiological and metabolic parameters in the mice, which were dose-dependently attenuated by ALA. ALA also significantly reduced HFD-induced hyperglycemia and insulin resistance in HFD-fed mice. Furthermore, ALA significantly upregulated the glycolytic enzymes GCK, HK-1 and PK, and the glycogen synthesis enzyme GS, and downregulated the gluconeogenic enzymes PEPCK and G6Pase, thus decreased glucose production, and promoted glycogen synthesis and glucose utilization in livers. Moreover, ALA markedly increased PKB/Akt and GSK3ß phosphorylation, and nuclear carbohydrate response element binding protein (ChREBP) expression in livers. Metformin produced similar effects as ALA in HFD-fed mice. CONCLUSION: ALA is able to sustain glucose homeostasis and prevent the development of NAFLD in HFD-fed mice.

Diosgenin relieves goiter via the inhibition of thyrocyte proliferation in a mouse model of Graves' disease.

AIM: To investigate the effects of diosgenin (Dio), a naturally occurring steroid saponin, on goiter formation in a mouse model of Graves' disease (GD) and the underlying mechanisms. METHODS: Female BALB/c mice were injected with adenovirus expressing the A subunit of thyrotropin receptor to induce GD. The mice were treated with Dio (20, 100 mg·kg(-1)·d(-1), ip) for 12 or 24 d. The serum levels of TT4 and TRAb were examined using radioimmunoassay and electrochemiluminescence. The size and morphology of thyroid glands were examined. Thyrocyte proliferation was determined using BrdU incorporation assay. The expression of proliferation-associated proteins IGF-1, NF-κB, cyclin D1, and PCNA in thyroids was analyzed using immunohistochemistry and real-time PCR. RESULTS: The GD mice showed significantly high serum levels of TRAb and TT4 compared to the normal mice. Treatment of the GD mice with Dio for 24 d dose-dependently reduced the TT4 level and thyroid size, but did not affect the abnormal level of TRAb. Furthermore, Dio treatment dose-dependently reversed the morphological changes and reduced excessive thyrocyte proliferation in thyroids of the GD mice. Dio treatment also dose-dependently reduced the mRNA and protein levels of IGF-1, NF-κB, cyclin D1, and PCNA in thyroids of the GD mice. CONCLUSION: Dio relieves goiter in a mouse model of GD through the inhibition of thyrocyte proliferation. The mechanisms involve the suppression of IGF-1, NF-κB, cyclin D1, and PCNA expression.

Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats.

AIM: Excess dietary fat intake can induce lipotoxicity in non-adipose tissues. The aim of this study was to observe the effects of dietary high-fat lard intake on thyroid in rats. METHODS: Male Sprague-Dawley rats were fed a high-fat lard diet for 24 weeks, and then the rats were fed a normal control diet (acute dietary modification) or the high-fat lard diet for another 6 weeks. The serum lipid profile, total thyroxine (TT4), free thyroxine (FT4) and thyrotropin (TSH) levels were determined at the 12, 18, 24 and 30 weeks. High-frequency ultrasound scanning of the thyroid glands was performed at the 24 or 30 weeks. After the rats were sacrificed, the thyroid glands were collected for histological and immunohistochemical analyses. RESULTS: The high-fat lard diet significantly increased triglyceride levels in both the serum and thyroid, and decreased serum TT4 and FT4 levels in parallel with elevated serum TSH levels. Ultrasonic imaging revealed enlarged thyroid glands with lowered echotexture and relatively heterogeneous features in the high-fat lard fed rats. The thyroid glands from the high-fat lard fed rats exhibited enlarged follicle cavities and flattened follicular epithelial cells under light microscopy, and dilated endoplasmic reticulum cisternae, twisted nuclei, fewer microvilli and secretory vesicles under transmission electron microscopy. Furthermore, the thyroid glands from the high-fat lard fed rats showed markedly low levels of thyroid hormone synthesis-related proteins TTF-1 and NIS. Acute dietary modification by withdrawal of the high-fat lard diet for 6 weeks failed to ameliorate the high-fat lard diet-induced thyroid changes. CONCLUSION: Dietary high-fat lard intake induces significant thyroid dysfunction and abnormal morphology in rats, which can not be corrected by short-term dietary modification.

Gene variants and the response to childhood obesity interventions: A systematic review and meta-analysis.

BACKGROUND: Multiple lifestyle-based childhood obesity interventions have been conducted to address childhood obesity, but individual's response to the universal intervention approach varied greatly. Whether gene variants related to children and adolescents' varied responses to obesity interventions remained unclear. AIMS: To determine the associations of gene variants with the changes in obesity- and metabolism-related indicators after obesity interventions in children and adolescents. METHODS: Ten databases and registers (including grey literature) were searched. The lifestyle-based obesity interventions in children and adolescents (≤18 years) that reported the changes in obesity- (body mass index (BMI), BMI Z-score, waist circumference (WC), waist-to-hip ratio (WHR), etc) and metabolism-related (glucose, cholesterol, etc) indicators by genotype after interventions were included. Our primary outcome was the mean difference of the changes in BMI Z-score by genotype after interventions, and secondary outcomes were changes in the remaining obesity- and metabolism-related indicators after interventions. We used the random-effects model to synthesize the results. RESULTS: This review included 50 studies (15,354 children and adolescents with overweight/obesity) covering 102 genes and 174 single nucleotide polymorphisms (SNPs). Approximately three-quarters of SNPs showed no evidence of association with the changes in obesity- or metabolic-related indicators after interventions. One quarter of SNPs were minorly associated with the changes in the BMI Z-score (median effect size: 0.001) with little clinical significance. Only 6 (12 %) studies focused on the accumulated effect of multiple gene variants. CONCLUSIONS: Gene variants that have been explored appear to play a minor role in lifestyle-based obesity interventions in children and adolescents. More high-quality studies based on the design of randomized controlled trials are needed to examine the accumulated effect of multiple gene variants in childhood obesity interventions. PROSPERO REGISTRY NUMBER: This systematic review and meta-analysis was registered at PROSPERO as CRD42022312177.

FTO genotype and body mass index reduction in childhood obesity interventions: A systematic review and meta-analysis.

Numerous guidelines have called for personalized interventions to address childhood obesity. The role of fat mass and obesity-associated gene (FTO) in the risk of childhood obesity has been summarized. However, it remains unclear whether FTO could influence individual responses to obesity interventions, especially in children. To address this, we systematically reviewed 12,255 records across 10 databases/registers and included 13 lifestyle-based obesity interventions (3980 children with overweight/obesity) reporting changes in body mass index (BMI) Z-score, BMI, waist circumference, waist-to-hip ratio, and body fat percentage after interventions. These obesity-related outcomes were first compared between children carrying different FTO genotypes (rs9939609 or its proxy) and then synthesized by random-effect meta-analysis models. The results from single-group interventions showed no evidence of associations between FTO risk allele and changes in obesity-related outcomes after interventions (e.g., BMI Z-score: -0.01; 95% CI: -0.04, 0.01). The results from controlled trials showed that associations between the FTO risk allele and changes in obesity-related outcomes did not differ by intervention/control group. To conclude, the FTO risk allele might play a minor role in the response to obesity interventions among children. Future studies might pay more attention to the accumulation effect of multiple genes in the intervention process among children.

[Effect of Chinese herbal compounds for blood activating stasis removing, qi benefiting Shen invigorating on high glucose stimulated proliferation of renal mesangial cells and expressions of fibronectin].

OBJECTIVE: To study effects of Chinese Herbal Compounds (CHC) for blood activating stasis removing (BASR), qi benefiting Shen invigorating (QBSI) on high glucose stimulated proliferation of renal mesangial cells (RMCs) and expressions of fibronectin (FN). METHODS: Rats' RMCs were dealt with high glucose and different concentrations of Chinese medicine for 24 and 48 h respectively. The proliferation of RMCs was detected with 4-A thiazolyl blue. mRNA expressions of FN was detected by real time quantitative PCR. The protein expression of FN was detected by ELISA. RESULTS: Compared with the control group, the proliferation obviously increased (P < 0.05, P < 0.01) after 24 and 48 h of treatment in the high glucose group, mRNA and protein expressions of FN also increased (P < 0.01). There was no statistical difference in the proliferation of RMCs or expressions of FN at 24 h between each CHC group and the high glucose group (P > 0.05). Compared with the high glucose group, the proliferation of RMCs and expressions of FN at 24 h each obviously decreased in the CHC group (P < 0.05, P < 0.01). CONCLUSIONS: High glucose could promote the proliferation of RMCs and induce expressions of FN. No obvious effect could be stimulated by CHC treatment for 24 h. The proliferation of RMCs, protein and mRNA expressions of FN could be reversed by CHC treatment for 48 h.

Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspase-dependent pathways.

Insulin-like growth factor-1 (IGF-1) is a growth factor of the thyroid that has been shown in our previous study to possess proliferative and antiapoptotic effects in FRTL-5 cell lines through the upregulation of cyclin D and Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). Diosgenin, a natural steroid sapogenin from plants, has been shown to induce apoptosis in many cell lines, with the exception of thyroid cells. In this report, we investigated the apoptotic effect and mechanism of diosgenin in IGF-1-stimulated primary human thyrocytes. Primary human thyrocytes were preincubated with or without IGF-1 for 24h and subsequently exposed to varying concentrations of diosgenin for different times. We found that diosgenin induced apoptosis in human thyrocytes pretreated with IGF-1 in a dose-dependent manner through the activation of caspase cascades. Moreover, diosgenin inhibited FLIP and activated caspase-8 in the FAS-related apoptotic pathway. Diosgenin increased the production of ROS, regulated the balance of Bax and Bcl-2 and cleaved caspase-9 in the mitochondrial apoptotic pathway. These results indicate that diosgenin induces apoptosis in IGF-1-stimulated primary human thyrocytes through two caspase-dependent pathways.

Chronic ethanol consumption increases the levels of chemerin in the serum and adipose tissue of humans and rats.

AIM: Chemerin is a new adipokine involved in adipogenesis and insulin resistance. Since ethanol affects the insulin sensitivity that is closely associated with adipokines. The aim of this study was to investigate the effects of ethanol on chemerin in humans and rats. METHODS: In the human study, 148 men who consumed alcohol for more than 3 years and 55 men who abstained from alcohol were included. Based on ethanol consumption per day, the drinkers were classified into 3 groups: low-dose (<15 g/d), middle-dose (15-47.9 g/d) and high-dose (≥48 g/d). Anthropometric measurements and serum parameters were collected. In the rat study, 27 male Wistar rats were randomly divided into 4 groups administered water or ethanol (0.5, 2.5, or 5 g·kg(-1)·d(-1)) for 22 weeks. The chemerin levels in the sera, visceral adipose tissue (VAT) and liver were measured using ELISA. RESULTS: In the high-dose group of humans and middle- and high-dose groups of rats, chronic ethanol consumption significantly increased the serum chemerin level. Both the middle- and high-dose ethanol significantly increased the chemerin level in the VAT of rats. In humans, triglyceride, fasting glucose, insulin and HOMA-IR were independently associated with chemerin. In rats, the serum chemerin level was positively correlated with chemerin in the VAT after adjustments for the liver chemerin (r=+0.768). High-dose ethanol significantly increased the body fat in humans and the VAT in rats. CONCLUSION: Chronic ethanol consumption dose-dependently increases the chemerin levels in the serum and VAT. The serum chemerin level is associated with metabolic parameters in humans. The increased serum chemerin level is mainly attributed to an elevation of chemerin in the VAT after the ethanol treatment.

Expert Consensus on Cognitive Dysfunction in Diabetes.

The incidence of diabetes is gradually increasing in China, and diabetes and associated complications, such as cognitive dysfunction have gained much attention in recent time. However, the concepts, clinical treatment, and prevention of cognitive dysfunction in patients with diabetes remain unclear. The Chinese Society of Endocrinology investigated the current national and overseas situation of cognitive dysfunction associated with diabetes. Based on research both in China and other countries worldwide, the Expert Consensus on Cognitive Dysfunction in Diabetes was established to guide physicians in the comprehensive standardized management of cognitive dysfunction in diabetes and to improve clinical outcomes in Chinese patients. This consensus presents an overview, definition and classification, epidemiology and pathogenesis, risk factors, screening, diagnosis, differential diagnosis, treatment, and prevention of cognitive dysfunction in patients with diabetes.

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.

Functional SNPs in the SCGB3A2 promoter are associated with susceptibility to Graves' disease.

Graves' disease (GD) is one of the most common human autoimmune diseases, and recent data estimated a prevalence of clinical hyperthyroidism of 0.25-1.09% in the population. Several reports have linked GD to the region 5q12-q33; and a locus between markers D5s436 and D5s434 was specifically linked to GD susceptibility in the Chinese population. In the present study, association analysis was performed using a large number of single-nucleotide polymorphisms (SNPs) at this locus in 2811 patients with GD recruited from different geographic regions of China. The strongest associations with GD in the combined Chinese Han cohorts were mapped to two SNPs in the promoter (pSNP) of SCGB3A2 [SNP76, rs1368408, P = 1.43 x 10(-6), odds ratio (OR) = 1.28 and SNP75, -623 - -622, P = 7.62 x 10(-5), OR = 1.32, respectively], a gene implicated in immune regulation. On the other hand, pSNP haplotypes composed of the SNP76 (rs1368408)+SNP74 (rs6882292) or SNP76+SNP75 (-623 approximately -622, AG/T) variants are correlated with high disease susceptibility (P = 0.0007, and P = 0.0192, respectively) in this combined Chinese Han cohort. Furthermore, these haplotypes were associated with reduced SCGB3A2 gene expression levels in human thyroid tissue, while functional analysis revealed a relatively low efficiency of SCGB3A2 promoters of the SNP76+SNP75 and SNP76+SNP74 haplotypes in driving gene expression. These results suggest that the SCGB3A2 gene may contribute to GD susceptibility.