Association and interaction analysis of diabetes mellitus and SCN10A for cardiovascular autonomic neuropathy in a Chinese population.

BACKGROUND: This study assessed the extent to which diabetes mellitus (DM) and SCN10A (rs7375036) and their interaction impact on cardiovascular autonomic neuropathy (CAN) susceptibility in a Chinese Han sample. METHOD: We performed a study in a cross-sectional dataset that included 419 patients with DM and 1557 controls who were genotyped for the presence of the SCN10A rs7375036 polymorphisms. Genotyping was performed by iPLEX technology. The associations of rs7375036 and DM with CAN was assessed by using univariate and multivariate logistic regression controlling for confounders. The interaction between rs7375036 and DM for CAN susceptibility on an additive scale was calculated by using the relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP), and the synergy index (S). RESULTS: The univariate logistic analyses failed to show an association between the SCN10A rs7375036 polymorphisms and CAN. Interestingly, a novel interaction effect of SCN10A rs7375036 and DM on CAN was assessed (p=0.055; RERI=3.515, 95% CI 1.829 to 5.805; AP=0.632, 95% CI -0.368 to 1.632; S=4.361, 95% CI 2.071 to 9.184). CONCLUSIONS: Our findings suggest that there are interaction effects of DM and SCN10A (rs7375036) that influence the development of CAN. TRIAL REGISTRATION NUMBER: NCT02461342.

An association analysis of lipid profile and diabetic cardiovascular autonomic neuropathy in a Chinese sample.

BACKGROUND: Recent studies have shown that triglyceride (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) are related to the prevalence of cardiovascular autonomic neuropathy (CAN). However, little is known about the association of lipid profile with diabetic cardiovascular autonomic neuropathy (DCAN), or its severity in the Chinese population. The purpose of this study is to explore the extent of this phenomenon using a Chinese sample. METHODS: A subgroup analysis on 455 diabetic patients with undiagnosed DCAN was performed to evaluate the relationships of lipids profile and DCAN. DCAN was diagnosed if there were at least two abnormal cardiovascular autonomic reflex test results, based on short-term heart rate variability tests. Multivariable logistic regression (MLR)was carried out to control potential confounders for determining the independent association of variables with DCAN in different models. RESULTS: MLR analysis indicated that TG was significantly and independently associated with DCAN when controlling for confounding factors (P < 0.1 for two models). Additionally, TG combined with TC (LRS-1) and LDL (LRS-2) was associated with this outcome (P < 0.1 for LRS-1 and LRS-2). CONCLUSION: Our findings indicate that TG and the severity of lipids profile is significantly and independently associated with DCAN, respectively. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02461472 , retrospectively registered 2 Jun, 2015.

[A clinical analysis of thyrotropin-secreting pituitary adenomas in 20 patients].

OBJECTIVE: To explore the clinical characteristics of thyrotropin-secreting pituitary adenomas. METHODS: A total of 20 patients with thyrotropin-secreting pituitary adenomas hospitalized in Shanghai Huashan Hospital from 2006 to 2013 were enrolled in the study. The clinical features, hormone levels, imaging findings, treatment and follow-up data were reviewed and analyzed. RESULTS: Most of the patients were young and middle-aged with (40.0 ± 14.5) years old. The disease duration varied from 1 month to 15 years. Among them, 13 cases (65%) presented with thyrotoxicosis and/or thyroid goiters and 9 (45%) presented with symptoms of intracranial compression. All patients had unsuppressed levels of thyroid stimulating hormone (TSH) with elevated levels of thyroid hormones. Pituitary lesions were found in all patients by neuroimaging. Pituitary adenomectomy, and/or somatostatin analogs and/or radiotherapy were applied in all patients after definitive diagnosis. Restored euthyroidism and shrinks pituitary adenomas with no progression were observed in 18 patients. Relapse was found in 1 patient and another patient was lost to follow up. CONCLUSIONS: Thyrotropin-secreting pituitary adenomas mainly present with thyrotoxicosis and/or pituitary tumor. Comprehensive therapy, including adenomectomy, somatostatin analogues and radiotherapy, is often needed for the management.

Artificial neural network models for prediction of cardiovascular autonomic dysfunction in general Chinese population.

BACKGROUND: The present study aimed to develop an artificial neural network (ANN) based prediction model for cardiovascular autonomic (CA) dysfunction in the general population. METHODS: We analyzed a previous dataset based on a population sample consisted of 2,092 individuals aged 30-80 years. The prediction models were derived from an exploratory set using ANN analysis. Performances of these prediction models were evaluated in the validation set. RESULTS: Univariate analysis indicated that 14 risk factors showed statistically significant association with CA dysfunction (P < 0.05). The mean area under the receiver-operating curve was 0.762 (95% CI 0.732-0.793) for prediction model developed using ANN analysis. The mean sensitivity, specificity, positive and negative predictive values were similar in the prediction models was 0.751, 0.665, 0.330 and 0.924, respectively. All HL statistics were less than 15.0. CONCLUSION: ANN is an effective tool for developing prediction models with high value for predicting CA dysfunction among the general population.

An increased level of haemoglobin A1C predicts a poorer clinical outcome in patients with acute pancreatitis.

OBJECTIVE: To compare the clinical features of acute pancreatitis (AP) in patients with and without diabetes. DESIGN, PATIENTS AND MEASUREMENTS: We retrospectively collected 318 patients with AP in two clinical centres from January 2009 to October 2010. Patients with a previous history of diabetes or with glycosylated haemoglobin A1c (HbA1c) higher than 6·5% were identified as having acute pancreatitis with diabetes (APD), while patients without a history of diabetes and in whom the HbA1c was not higher than 6·5% were considered as AP only. The clinical characteristics and prognosis data of these patients were analysed. Survival curves were plotted according to the Kaplan-Meier method. Cox proportional hazard regression was used to test the association between the clinical prognostic factors and mortality in patients with AP. RESULTS: In total, 318 patients with AP were enrolled. Among them, 40 had APD and 278 had AP; thus, in this study, the prevalence of diabetes in AP was 12·6% (40/318). Twenty-five per cent (10/40) of the APD cases were indentified using HbA1c. The mortality rate was significantly higher in the APD group (15·0%, 6/40) than that in the AP group (1·1%, 3/278). Survival curves showed that there was a significant survival difference between the APD group and AP group via the log-rank test. Multivariate Cox regression analysis showed that sex, age, diastolic blood pressure, body mass index (BMI) and C-peptide were significantly associated with mortality. Compared with AP patients, subjects with APD had significantly longer time from initial symptoms to admission [1·6 (95% CI: 0·5-3·2) vs 0·9 (95% CI: 0·1-2·2) days], older age of onset (57·2 ± 11·0 vs 44·3 ± 7·8 years), higher levels of glucose (13·9 ± 8·2 vs 7·3 ± 4·1 mm), higher levels of HbA1c [8·5 (95% CI: 6·6-11·4)%vs 5·9 (95% CI: 4·9-6·4)%], lower levels of C-peptide (0·882 ± 0·337 vs 2·621 ± 0·526 ng/ml) and longer duration of hospitalization (18·3 ± 4·6 vs 13·2 ± 5·1 day). Electrocardiograms showed that APD patients had a significantly higher risk of heart ischaemia than AP patients (22/40 vs 20/278). CONCLUSIONS: HbA1c may be a useful marker to identify unrecognised diabetes in patients with acute pancreatitis; this group of patients has a higher in hospital mortality.

LOC66273 isoform 2, a novel protein highly expressed in white adipose tissue, induces adipogenesis in 3T3-L1 cells.

Obesity results in part from altered adipocyte metabolism and enhanced adipogenesis. However, the factors that influence insulin-independent differentiation of preadipocytes in response to excess intake of dietary energy remain poorly understood. Based on our recent finding that LOC66273 isoform 2 (LI2), a gene that encodes a novel Mth938 domain-containing protein, is highly expressed in white adipose tissues, we hypothesized that LI2 plays an important role in adipogenesis. Plasmid pcDNA3.1-LI2 was electroporated into 3T3-L1 preadipocytes to overexpress the LI2 protein. Synthetic siRNA was transfected into 3T3-L1 cells to knockdown endogenous LI2. Using constitutively active and potent siRNA against LI2, we determined cell morphology, cell viability, and adipocytic factors in 3T3-L1 preadipocytes. Our results indicated that LI2 was sufficient to drive preadipocyte differentiation via modulating the phosphorylation level and transcriptional activity of CREB, coincident with expression of several adipogenic regulators and mature adipocyte markers, without insulin treatment. In addition, overexpression of the LI2 protein inhibited preadipocyte growth, whereas knockdown of the LI2 protein resulted in preadipocyte apoptosis via caspase-3 activation during adipogenesis. These results indicated that LI2 might function to switch preadipocytes from proliferation to differentiation and to maintain the viability of preadipocytes during adipogenesis by regulating the caspase-3 pathway. Our findings highlight the importance of LI2 in the formation of new adipocytes, thus helping understand the mechanisms responsible for insulin-independent adipogenesis in mammals.

Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice.

Secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is a poorly characterized secreted protein of largely unknown physiological function. Here we demonstrate that scEMC10 is upregulated in people with obesity and is positively associated with insulin resistance. Consistent with a causal role for scEMC10 in obesity, Emc10-/- mice are resistant to diet-induced obesity due to an increase in energy expenditure, while scEMC10 overexpression decreases energy expenditure, thus promoting obesity in mouse. Furthermore, neutralization of circulating scEMC10 using a monoclonal antibody reduces body weight and enhances insulin sensitivity in obese mice. Mechanistically, we provide evidence that scEMC10 can be transported into cells where it binds to the catalytic subunit of PKA and inhibits its stimulatory action on CREB while ablation of EMC10 promotes thermogenesis in adipocytes via activation of the PKA signalling pathway and its downstream targets. Taken together, our data identify scEMC10 as a circulating inhibitor of thermogenesis and a potential therapeutic target for obesity and its cardiometabolic complications.

Autonomic nervous function and baroreflex sensitivity in hypertensive diabetic patients.

OBJECTIVE: Little is known about how the cardiac autonomic nervous function (CAN) changes with gradually increasing systolic blood pressure (SBP). This study investigated cardiac autonomic nervous function in diabetic patients and controls with different grades of SBP. METHODS AND RESULTS: We measured heart rate variability (HRV) and spontaneous baroreflex sensitivity (BRS) by power spectral analysis in 118 Chinese type-2 diabetic patients and 137 age-matched controls. Subjects were further subdivided into 4 SBP groups. Results showed total HRV and BRS values were significantly lower in several diabetic SBP groups. Total HRV and BRS decreased with increasing SBP, with significant differences in the 140-159 mm Hg or 160-179 mm Hg groups compared with other groups of diabetic and control subjects. CONCLUSIONS: We found that HRV and BRS can reflect cardiovascular autonomic dysfunction of diabetes when accompanied by hypertension. In our selected Chinese diabetic and control subjects, HRV and BRS parameters were influenced by gradually increasing SBP.

Liver fibrosis is independently associated with diabetic peripheral neuropathy in type 2 diabetes mellitus.

AIMS/INTRODUCTION: Non-alcoholic fatty liver disease and type 2 diabetes mellitus are closely related, and often occur simultaneously in patients. Type 2 diabetes increases the risk of diabetic peripheral neuropathy, resulting in intolerable pain and extremity amputation that reduces the quality of life. However, the role of non-alcoholic fatty liver disease in the pathogenesis of diabetic peripheral neuropathy remains unclear. Thus, we evaluated the correlation of liver fibrosis and steatosis, which are representative histological morphologies of non-alcoholic fatty liver disease, with diabetic peripheral neuropathy in type 2 diabetes patients. MATERIALS AND METHODS: Five hundred twenty individuals with type 2 diabetes were recruited. All the patients were detected nerve conduction study for diabetic peripheral neuropathy and fibro touch for liver steatosis and fibrosis. Correlation of DPN with liver steatosis and fibrosis were analysed with binary logistic analysis. RESULTS: Among the 520 patients, the prevalence of liver steatosis, fibrosis and diabetic peripheral neuropathy was 63.0% (n = 328), 18.1% (n = 94) and 52.1% (n = 271), respectively. The prevalence of diabetic peripheral neuropathy was significantly elevated in patients with liver steatosis (55.7 vs 44.9%, P = 0.03) and fibrosis (61.5 vs 50%, P = 0.04), and it increased as liver stiffness measurement increased. Additionally, both hepatic steatosis (odds ratio 1.48, 95% confidence interval 1.04-2.11, P = 0.03) and fibrosis (odds ratio 1.60, 95% confidence interval 1.02-2.51, P = 0.04) were correlated with diabetic peripheral neuropathy. After adjusting for age, sex, weight, height, body mass index, waist hip ratio, duration of type 2 diabetes, blood glucose, homeostatic model assessment of insulin resistance, blood pressure, serum lipid, liver enzyme, urea, uric acid, creatinine and inflammatory factors, liver fibrosis remained associated with diabetic peripheral neuropathy (odds ratio 2.24, 95% confidence interval 1.11-4.53, P = 0.02). CONCLUSIONS: The prevalence of diabetic peripheral neuropathy was elevated in patients with liver steatosis and fibrosis. Liver fibrosis was also independently associated with an increased risk of diabetic peripheral neuropathy.

Interaction of TPPP3 with VDAC1 Promotes Endothelial Injury through Activation of Reactive Oxygen Species.

Endothelial injury plays a critical role in the pathogenesis of cardiovascular disorders and metabolic-associated vascular complications which are the leading cause of death worldwide. However, the mechanism underlying endothelial dysfunction is not completely understood. The study is aimed at investigating the role of tubulin polymerization-promoting protein family member 3 (TPPP3) in palmitic acid- (PA-) induced endothelial injury. The effect of TPPP3 on human umbilical vein endothelial cells (HUVECs) was determined by evaluating apoptosis, tube formation, and reactive oxygen species (ROS) production. TPPP3 silencing inhibited PA overload-induced apoptosis and production of ROS, along with the alteration of apoptosis-related key proteins such as BCL-2 and Bax. Mechanically, voltage-dependent anion channel 1 (VDAC1) was identified as a novel functional binding partner of TPPP3, and TPPP3 promoted VDAC1 protein stability and its activity. Further studies indicated that TPPP3 could promote apoptosis, ROS production, tube formation, and proapoptotic protein expression and reduce antiapoptotic protein expression through increasing VDAC1 expression under mildly elevated levels of PA. Collectively, these results demonstrated that TPPP3 could promote PA-induced oxidative damage in HUVECs via a VDAC1-dependent pathway, suggesting that TPPP3 might be considered as a potential therapeutic target in vascular disease.

Impaired fasting glucose and the prevalence and severity of angiographic coronary artery disease in high-risk Chinese patients.

We assessed the relation between different fasting plasma glucose (FPG) levels of 5.6 to 6.9 mmol/L and the prevalence and severity of angiographic coronary artery disease (CAD) in high-risk Chinese patients. Among 512 subjects who were to undergo coronary angiography for the confirmation of suspected myocardial ischemia, 409 subjects were enrolled and categorized into 3 groups based on FPG levels: (1)

High prevalence of chronic kidney disease in population-based patients diagnosed with type 2 diabetes in downtown Shanghai.

OBJECTIVE: This study aimed to evaluate the prevalence of chronic kidney disease (CKD) and the risk factors associated with CKD among Chinese patients diagnosed with type 2 diabetes aged over 30 in downtown Shanghai and to assess the relationship between CKD and diabetic retinopathy (DR). METHODS: We investigated 1039 Chinese patients diagnosed with type 2 diabetes aged over 30 by randomized cluster sampling in downtown Shanghai, and 1009 patients in this study were analyzed based on data integrity. Body measurements including height, weight, waist circumference and hip circumference, resting blood pressure, fasting blood measures, and urinary albumin-to-creatinine ratio (ACR), as well as the digitally stored fundus images, were investigated. Glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault equation. The prevalence of CKD was calculated, and the risk factors associated with CKD were evaluated using stepwise logistic regression. The relationship between CKD and DR was evaluated using Spearman correlation and the chi-square test. RESULTS: The following were the results found in this study: (a) The prevalence rate of CKD (Stages 1-5) was 63.9% in Chinese patients diagnosed with type 2 diabetes, 8.8% in those with CKD Stage 1, 22.3% in those with CKD Stage 2, and 32.8% in those with CKD Stages 3-5 (GFR<60 ml/min/1.73 m(2)). The prevalence of CKD increased with age. (b) CKD patients were older and had higher duration of diabetes, systolic blood pressure, urea nitrogen, uric acid, creatinine, and ACR of the first urine than those without CKD. (c) Male patients had a higher percentage of CKD Stages 3-5, and female patients had a higher percentage of CKD Stages 1-2. (d) CKD was significantly associated with duration of diabetes, older age, systolic blood pressure, and serum urea nitrogen based on logistic regression analysis. (e) Of the patients without CKD, 15.6% had DR, and of those with CKD, 27.6% had DR. The decrease in GFR was significantly correlated with DR after controlling for sex, age, and albuminuria staging. CONCLUSION: The high prevalence of CKD observed in Chinese patients diagnosed with type 2 diabetes aged over 30 in downtown Shanghai was similar to that in Western patients, and the cause of CKD is likely to be any of the following: type 2 diabetes, IgA nephropathy, hypertension, or any combination of these. The screening program for GFR in type 2 diabetic patients should be performed even on those with normoalbuminuria. The decrease in GFR might predict the occurrence of DR among patients diagnosed with type 2 diabetes.

Spironolactone Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats.

Spironolactone (SPR) has been shown to protect diabetic cardiomyopathy (DCM), but the specific mechanisms are not fully understood. Here, we determined the cardioprotective role of SPR in diabetic mice and further explored the potential mechanisms in both in vivo and in vitro models. Streptozotocin- (STZ-) induced diabetic rats were used as the in vivo model. After the onset of diabetes, rats were treated with either SPR (STZ + SPR) or saline (STZ + NS) for 12 weeks; nondiabetic rats were used as controls (NDCs). In vitro, H9C2 cells were exposed to aldosterone, with or without SPR. Cardiac structure was investigated with transmission electron microscopy and pathological examination; immunohistochemistry was performed to detect nitrotyrosine, collagen-1, TGF-ß1, TNF-α, and F4/80 expression; and gene expression of markers for oxidative stress, inflammation, fibrosis, and energy metabolism was detected. Our results suggested that SPR attenuated mitochondrial morphological abnormalities and sarcoplasmic reticulum enlargement in diabetic rats. Compared to the STZ + NS group, cardiac oxidative stress, fibrosis, inflammation, and mitochondrial dysfunction were improved by SPR treatment. Our study showed that SPR had cardioprotective effects in diabetic rats by ameliorating mitochondrial dysfunction and reducing fibrosis, oxidative stress, and inflammation. This study, for the first time, indicates that SPR might be a potential treatment for DCM.

Exogenous Pancreatic Kallikrein Improves Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetes.

Aims: To evaluate the protective effects of exogenous pancreatic kallikrein (PKK) treatment on diabetic cardiomyopathy (DCM) and explore the underlying mechanisms. Methods and Results: Streptozotocin (STZ)-induced diabetic rats, a type 1 diabetic model, were treated with either PKK or saline for 12 weeks. Non-diabetic rats were used as controls. PKK administration attenuated the mitochondria swelling, Z line misalignments, myofibrosis and interstitial collagen accumulation in diabetic myocardial tissue. The oxidative stress imbalance including increased nitrotyrosine, decreased anti-oxidative components such as nuclear receptor nuclear factor like 2 (Nrf2), glutathione peroxidase 1(GPx-1), catalase (CAT) and superoxide dismutase (SOD), were recovered in the heart of PKK-treated diabetic rats. In diabetic rats, protein expression of TGF-ß1 and accumulation of collagen I in the heart tissues was decreased after PKK administration. Markers for inflammation were decreased in diabetic rats by PKK treatment. Compared to diabetic rats, PKK reversed the degradation of IκB-α, an inhibitive element of heterotrimer nuclear factor kappa B (NF-κB). The endothelial nitric oxide synthase (eNOS) protein and myocardial nitrate/nitrite were impaired in the heart of diabetic rats, which, however, were restored after PKK treatment. The sarcoplasmic reticulum Ca2+-ATPase 2 (SERCA2) and phospholamban (PLN) were mishandled in diabetic rats, while were rectified in PKK-treated diabetic rats. The plasma NT-proBNP level was increased in diabetic rats while was reduced with PKK treatment. Conclusion: PKK protects against DCM via reducing fibrosis, inflammation, and oxidative stress, promoting nitric oxide production, as well as restoring the function of the calcium channel.

Easier operation and similar power of 10 g monofilament test for screening diabetic peripheral neuropathy.

Objective The 10 g Semmes-Weinstein monofilament evaluation (SWME) of 4 sites on each foot is recommended for distal symmetric polyneuropathy screening and diagnosis. A similar method has been proposed to diagnose 'high-risk' (for ulceration) feet, using 3 sites per foot. This study compared the effectiveness of SWME for testing 3, 4 and 10 sites per foot to identify patients with diabetic neuropathy. Methods We included 3497 subjects in a SWME of 10 sites; records from the 10-site SWME were used for a SWME of 3 and 4 sites. Neuropathy symptom scores and neuropathy deficit scores were evaluated to identify patients with diabetic peripheral neuropathy. Results The sensitivities of the 10 g SWME for 3, 4 and 10 sites were 17.8%, 19.0% and 22.4%, respectively. The Kappa coefficients for the SWME tests of 3, 4 and 10 sites were high (range: 0.78-0.93). Conclusions There were no significant differences in the effectiveness of 3-, 4- and 10-site SWME testing for diabetic peripheral neuropathy screening. SWME testing of 3 sites on each foot may be sufficient to screen for diabetic neuropathy.

Correction: Comparison of Prediction Model for Cardiovascular Autonomic Dysfunction Using Artificial Neural Network and Logistic Regression Analysis.

[This corrects the article DOI: 10.1371/journal.pone.0070571.].

Recombinant SFRP5 protein significantly alleviated intrahepatic inflammation of nonalcoholic steatohepatitis.

BACKGROUND: Secreted frizzled-related protein 5 (SFRP5) is an anti-inflammatory adipokine modulating metabolism dysfunction. This study aims to observe the effect of recombinant SFRP5 protein on nonalcoholic steatohepatitis (NASH). METHODS: We set up a prokaryotic expression system and purified the recombinant SFRP5 protein. Recombinant SFRP5 protein was further identified by SDS-PAGE, western blot, high performance liquid chromatography (HPLC), protein mass spectrometry and in vitro Wnt5a-binding test. NASH mouse model was induced by methionine and choline deficient diet (MCDD) for 2 weeks. SFRP5 treatment group received intraperitoneal injection with a dosage of 10µg/kg SFRP5 twice a day for 2 weeks. Saline was used as control. Inflammation and fatty lesion score of liver tissue pathology and serum transaminase level were compared. RESULTS: The purity of recombinant SFRP5 protein is 90% identified by HPLC. Its molecule size is 36,096.08 tested by mass spectrometry. Recombinant SFRP5 can specifically bind with Wnt5a which verifies its activity in vitro. The endotoxin level of this recombinant protein is 0.01EU/µg-0.1EU/µg and is suitable for animal experiment. SFRP5 can significantly improve liver inflammation (SFRP5 vs. control, 1.40 ± 0.70 vs. 2.00 ± 0.47, P < 0.05) as well as fatty lesion scores (SFRP5 vs. control, 1.40 ± 0.97 vs. 2.20 ± 0.63, P < 0.05), and lower ALT and AST levels. The mRNA expression of proinflammatory adipokines (IL-1ß, IL-6, TNFα and MCP-1) in liver was down-regulated significantly after SFRP5 intervention. Immunohistochemistry and quantitative PCR revealed a dramatically down-regulation of F4/80 in liver after SFRP5 treatment. CONCLUSIONS: Recombinant SFRP5 protein significantly alleviated NASH induced by MCDD.

An evaluation of the International Diabetes Federation definition of metabolic syndrome in Chinese patients older than 30 years and diagnosed with type 2 diabetes mellitus.

The objective of the study was to determine the most accurate metabolic syndrome (MS) definition among the definitions proposed by the International Diabetes Federation (IDF), the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [ATPIII]), and the World Health Organization (WHO) and to evaluate the cutoff point of waist circumference using the IDF definition for optimally defining MS in the Chinese population. One thousand thirty-nine Chinese patients older than 30 years and diagnosed with type 2 diabetes mellitus were investigated by randomized cluster sampling in the Shanghai downtown, and 1008 patients were analyzed in this study. Body mass measurements, resting blood pressure, fasting blood measures, and carotid atherosclerotic measurements including common carotid artery intima-media thickness (IMT) and carotid plaque were investigated. The IDF definition was compared with the other 2 definitions, and the carotid atherosclerosis was evaluated among the patients according to these definitions. (1) The MS prevalence was 50.0%, 55.7%, and 70.0% under the IDF, ATPIII, and WHO definitions, respectively. (2) The percentage of all the participants categorized as either having or not having the MS was 69.9% (under the IDF and ATPIII definitions) and 70.2% (under the IDF and WHO definitions). (3) Common carotid artery IMT of patients with MS determined by the IDF definition was thicker than those determined by the WHO and ATPIII definitions, and the percentage of carotid plaque of patients with MS determined by the IDF definition was greater than those determined by the WHO and ATPIII definitions. (4) When the cutoff point of waist circumference in men determined by the IDF definition was modified from 90 to 85 cm, common carotid artery IMT of the emerging male patients with MS was thicker than that of the male patients with MS determined by the original IDF definition. In conclusion, the prevalence of MS was 50.0%, 55.7%, and 70.0% under the IDF, ATPIII, and WHO definitions, respectively. The preferable IDF definition served as a better predictor of cardiovascular disease risk in the Chinese patients diagnosed with type 2 diabetes mellitus compared with the ATPIII and WHO definitions. The modified cutoff point of waist circumference in men under the IDF definition specific for the Chinese population (from 90 to 85 cm) might be more suitable for predicting atherosclerosis.

A study for association and interaction analysis to metabolic syndrome and the ESR1 gene on cardiovascular autonomic neuropathy in a Chinese Han population.

BACKGROUND: The aim of this study was to investigate the association and interaction of metabolic syndrome (MetS) and estrogen receptor alpha 1 (ESR1) gene polymorphisms on cardiovascular autonomic neuropathy (CAN). METHODS: A large-scale, population-based study was conducted to analyze the interaction of MetS and ESR1 gene polymorphisms to CAN, including a total of 1977 Chinese subjects. The most common studied single nucleotide polymorphism of ESR1 gene-rs9340799, was genotyped. Multiple logistic regression (MLR) was performed to evaluate the interaction effect of environmental variables and gene polymorphisms. Interaction on an additive scale can be calculated by using the relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP), and the synergy index (S). RESULTS: After controlling potential confounders, MLR showed that significant association between MetS and CAN (p < 0.001). Interestingly, we found that the participants with MetS bearing the minor allele G had an increased CAN prevalence comparing those with allele A (p = 0.045), and a positive interaction was estimated by using RETI = 0.396 (95 % CI 0.262 to 0.598), AP = 0.216 (95 % CI -0.784 to 1.216) and S = 1.906 (95 % CI 0.905 to 4.015). CONCLUSION: The present findings suggest that MetS is significantly associated with CAN and provide evidence for the hypothesis that MetS and ESR1 gene polymorphism (rs9340799) have interactive effects on CAN. ClinicalTrials gov Identifier NCT02461342.

UNC50 prompts G1/S transition and proliferation in HCC by regulation of epidermal growth factor receptor trafficking.

BACKGROUND: UNC50 has long been recognized as a Golgi apparatus protein in yeast, and is involved in nicotinic receptor trafficking in Caenorhabditis elegans, but little is known about UNC50 gene function in human biology despite it being conserved from yeast to high eukaryotes. OBJECTIVES: We investigated the relation between UNC50 and human hepatocellular carcinoma (HCC) and the potential mechanisms underlying HCC development. METHODS: UNC50 mRNA expression patterns in 12 HCC and adjacent non-cancerous tissues determined using northern blotting were confirmed by real-time PCR in another 44 paired tissues. Microarray experiments were used to screen for global effects of UNC50 knockdown in the Hep3B cell line, and were confirmed by real-time PCR, western blotting, flow cytometry, and tetrazolium assay in both UNC50 overexpression and knockdown Hep3B cells. RESULTS: UNC50 expression levels were upregulated in HCC tissues in comparison with the adjacent non-cancerous tissues. UNC50 knockdown reduced mRNA levels of the downstream targets of the epidermal growth factor receptor (EGFR) pathway: cyclin D1 (CCND1), EGF, matrix metalloproteinase-7 (MMP7), aldose reductase-like 1 (AKR1B10), cell surface-associated mucin 1 (MUC1), and gastrin (GAST). Moreover, UNC50 influenced EGF, inducing cell cycle entry by affecting cell surface EGFR amounts. CONCLUSIONS: UNC50 may plays some roles in HCC progression by affecting the EGFR pathway.