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.

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.

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.

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.

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.].

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.

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.

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.

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.

Peripheral neuropathy is associated with insulin resistance independent of metabolic syndrome.

BACKGROUND: To determine the association of insulin resistance, metabolic syndrome (MetS) with peripheral neuropathy (PN). METHODS: This cross-sectional study consisted of 2035 subjects in Shanghai who were classified as with MetS and without MetS. The new International Diabetes Federation (IDF) criterion was used to define MetS. HOMA-IR was applied to evaluate insulin resistance. All subjects underwent complete foot examination. PN was assessed according to the neuropathy symptom and neuropathy disability scores. Binary logistic regression was performed to analyze the contributions of insulin resistance, features of MetS to PN. RESULTS: (1) The percentage of PN was 4.0% in our study. Patients with MetS (47.7%) had a higher percentage of PN (5.5% vs. 2.6%, respectively, P = 0.001). With the components of MetS increased (non-MetS, three, four, five), a linear increase in the proportion of peripheral neuropathy was observed (2.6%, 4.8%, 5.6% and 7.2%; respectively, P for trend = 0.001). (2) In patients with PN, the average age of patients was significantly older than the corresponding non-PN patients. Waist circumference, fasting blood glucose, HbA1c, proportion of treatment for diabetes and hypertension were significantly higher in PN group compared with non-PN group in MetS patients. (3) The frequency of dysglycemia was the highest in PN patients both with and without MetS (96.2% and 82.1%, P = 0.084). (4) After adjusting for gender and smoking history, the PN was associated with MetS [odds ratio (OR) 2.0; 95% confidence interval (CI) 1.2, 3.2; P = 0.006], and age (OR 1.1; 95% CI 1.1, 1.1; P < 0.001). When HOMA-IR was added to this binary logistic regression, the association of PN with MetS disappeared (P = 0.110), but the PN was still associated with HOMA-IR (OR 1.2; 95% CI 1.1, 1.4, P < 0.001). CONCLUSIONS: In metabolic syndrome, insulin resistance might play an important role in the development of peripheral neuropathy.

Successful diagnosis of hypothalamitis using stereotactic biopsy and treatment: a case report.

Existing methods could not discriminate between inflammation and other diseases, which might occur in hypothalamus, such as neurogliocytoma, germinoma, lymphoma, and so on. Given its location in the brain, it was not practical to obtain tissue using standard surgical methods. We reported the first case of a patient with hypothalamus lesion, who was diagnosed as hypothalamitis by stereotactic biopsy. This precise diagnosis allowed proper medical treatments. We reported a case of a patient with hypothalamus lesion. To confirm the diagnosis, with informed consent from the family, a successful stereotactic hypothalamic biopsy was performed by neurosurgeons. Immunohistochemical results of biopsy specimens from the hypothalamus lesion revealed inflammatory infiltrates, which were composed mainly of lymphocytes, plasma cells, and histiocytes, and were stained with leucocyte common antigen (LCA), κ 1, and cluster of differentiation 18. Final pathological diagnosis was lymphoplasmacytic proliferative, granuloma-like inflammatory pseudotumor, with immunoglobulin G deposition. Based on the pathological diagnosis, we treated the patient with glucocorticoid and azathioprine. Remarkable improvements were observed in both magnetic resonance imaging (MRI) and patient's symptoms. Stereotactic biopsy for intracranial lesions was a reliable and relatively safe procedure, even for hypothalamus. It was an effective method with high diagnostic yield. With correct diagnosis, it was much easier to choose correct treatment.

The value of prolactin in inferior petrosal sinus sampling with desmopressin stimulation in Cushing's disease.

Prolactin may reduce false-negative results in diagnosing Cushing's disease (CD) during inferior petrosal sinus sampling (IPSS). Prolactin normalization could improve the accuracy of IPSS in predicting adenoma lateralization in CD. However, none of the previous studies had involved the use of desmopressin during IPSS. Our objective was to examine the utility of prolactin measurement during IPSS with desmopressin stimulation. We conducted a retrospective analysis of 40 patients (including 31 females) with ACTH-dependent Cushing's syndrome who underwent IPSS between 2010 and 2013. Thirty-eight CD patients were partitioned into true positive (n = 35) and false negative (n = 3). The proportion of improper IPSS venous sampling defined by corresponding IPS:P (inferior petrosal sinus to peripheral) prolactin ratio <1.8 was significantly different between two groups (P = 0.004). Applying a prolactin-normalized ACTH IPS:P ratio >0.8 cutoff could increase the sensitivity of IPSS to 38/38 (100 %). Among the 31 patients with histopathologically proven adenoma localization, correct prediction of adenoma lateralization was obtained in 14/31 (45 %) patients by a peak intersinus ACTH gradient of ≥1.4 in baseline and was not improved by desmopressin stimulation. Left-right intersinus gradients of unilateral prolactin-adjusted ACTH IPS:P ratios could increase the correct prediction of adenoma lateralization to 20/31 (65 %) in baseline and 24/31 (77 %) (P = 0.006) after desmopressin stimulation, respectively. Prolactin is helpful to adjust negative results of IPSS with desmopressin stimulation. It may improve the accuracy in predicting adenoma lateralization in CD as well.

Bayesian estimation of cardiovascular autonomic neuropathy diagnostic test based on short-term heart rate variability without a gold standard.

OBJECTIVE: To evaluate the reference values for short-term heart rate variability (HRV), estimate the performance of cardiovascular autonomic neuropathy (CAN) diagnostic tests in the absence of a gold standard, and assess CAN prevalence in our dataset. SETTING: Community and hospital health centre. PARTICIPANTS: Of 2092 subjects available for data analysis, 371 healthy subjects were selected so the reference values for the short-term HRV test could be evaluated. An external dataset contained 88 subjects who completed both the short-term HRV test and Ewing's test. INTERVENTION: Collection of information on clinical outcome. PRIMARY AND SECOND OUTCOME MEASURES: Cardiovascular autonomic function evaluated by using the short-term HRV test and/or Ewing's test. RESULTS: Cut-off points of 356.13, 55.45 and 36.64 ms2 were set for total power, low frequency and high frequency (HF), respectively. The diagnostic test for CAN based on the mentioned reference value was created. The HRV test had a high sensitivity (80.01-85.09%) and specificity (82.30-85.20%) for CAN. In addition, the non-inferiority test rejected the null hypothesis that the performance of the HRV test was inferior to that of Ewing's test (p<0.05). The estimated CAN prevalence was 14.92% and 29.17% in the total sample and patients with diabetes, respectively. CONCLUSIONS: Our findings provided reference values for short-term HRV, which were used for the CAN diagnostic test with high sensitivity and specificity. The estimated CAN prevalence was high in the Chinese population.

Association and predictive value analysis for resting heart rate and diabetes mellitus on cardiovascular autonomic neuropathy in general population.

BACKGROUND: The purpose of this study was to evaluate the predictive value of DM and resting HR on CAN in a large sample derived from a Chinese population. MATERIALS AND METHODS: We conducted a large-scale, population-based, cross-sectional study to explore the relationships of CAN with DM and resting HR. A total of 387 subjects were diagnosed with CAN in our dataset. The associations of CAN with DM and resting HR were assessed by a multivariate logistic regression (MLR) analysis (using subjects without CAN as a reference group) after controlling for potential confounding factors. The area under the receiver-operating characteristic curve (AUC) was used to evaluate the predictive performance of resting HR and DM. RESULTS: A tendency toward increased CAN prevalence with increasing resting HR was reported (P for trend <0.001). MLR analysis showed that DM and resting HR were very significantly and independently associated with CAN (P < 0.001 for both). Resting HR alone or combined with DM (DM-HR) both strongly predicted CAN (AUC = 0.719, 95% CI 0.690-0.748 for resting HR and AUC = 0.738, 95% CI 0.710-0.766 for DM-HR). CONCLUSION: Our findings signify that resting HR and DM-HR have a high value in predicting CAN in the general population.

[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.

The analysis of a reference value for baroreflex sensitivity and cardiovascular autonomic neuropathy prevalence in a Chinese population.

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is rapidly growing in all populations worldwide. Baroreflex sensitivity (BRS) is easily applied as a diagnostic test to a large number of individuals in the general population. However, no study has reported the normal reference values of BRS for the CAN diagnostic test in a Chinese population. The aim of this study was to estimate the normative reference value of BRS, and assess CAN prevalence in our cross-sectional dataset. METHODS: We conducted a large-scale, community-based, cross-sectional study in a Chinese population. We performed data analysis on 2,092 subjects. Cardiovascular autonomic function was assessed using spontaneous BRS. A total of 349 healthy subjects were used to perform analysis for the reference value for BRS. The CAN prevalence was calculated in the overall sample, and in patients with diabetes mellitus, patients with hypertension and patients with metabolic syndrome. RESULTS: In the overall sample, the reference value for total power (TP.brs) was more than 1.96 ms/mmHg. The cut-off points of 1.74 ms/mmHg and 2.53 ms/mmHg were set as high frequency (HF.brs) and low frequency (LF.brs), respectively. CAN diagnostic tests based on the reference value were performed. The estimated CAN prevalence in the overall sample was 20.41% using the BRS test. CAN prevalence was 33.18%, 28.69% and 28.57% in patients with diabetes mellitus, patients with hypertension and patients with metabolic syndrome, respectively. CONCLUSIONS: Our findings provided reference values for BRS. Estimated CAN prevalence was high in this Chinese population, which has become a major public health problem in China.