Junping Wen

Associations Between Age at Menarche and Menopause With Cardiovascular Disease, Diabetes, and Osteoporosis in Chinese Women

CONTEXT Ages at menarche and menopause are associated with cardiovascular disease (CVD), diabetes, and osteoporosis in Caucasian women, but associations remain unexplored in Chinese women. OBJECTIVE The purpose of this study was to assess associations between age at menarche and menopause with CVD, diabetes, and osteoporosis in Chinese women. DESIGN AND SETTING A cross-sectional, population-based study was conducted in Fujian, China, from June 2011 to January 2012. PARTICIPANTS Among 6242 women aged 21 to 92 years, 3304 postmenopausal women were enrolled, excluding premenopausal women (n = 2527), those with unreported ages at menarche and menopause (n = 138), those with unrecorded physical measurements (n = 203), and those with menarche age <8 years or >20 years (n = 70). MAIN OUTCOME MEASURES An oral glucose tolerance test, a 12-lead resting electrocardiogram, and calcaneus quantitative ultrasound were performed. RESULTS No significant associations were found between menarche age, diabetes, and osteoporosis (both P > .05); later menarche (>18 years) was significantly associated with lower CVD risk (odds ratio = 0.71, 95% confidence interval, 0.57-0.89; P = .002). Menopause age was not associated with diabetes; higher menopause age was associated with decreasing CVD risk (P for trend = .020) and earlier menopause (≤46 years) with significantly higher osteoporosis risk (odds ratio = 1.59, 95% confidence interval, 1.07-2.36; P = .023). CONCLUSIONS In China, ages at menarche and menopause are not associated with diabetes. Later menarche and menopause are associated with decreasing CVD risk and earlier menopause with higher osteoporosis risk. Menarche and menopause history may help identify women with increased risk of developing CVD and osteoporosis.

Genetic variations in CYP17A1, CACNB2 and PLEKHA7 are associated with blood pressure and/or hypertension in she ethnic minority of China

OBJECTIVES Two large-scale genome-wide association studies (GWAs) have identified multiple variants associated with blood pressure (BP) or hypertension. The present study was to investigate whether some variations were associated with BP traits and hypertension or even prehypertension in adult She ethnic minority of China. METHODS The population of the present study comprised 4460 (1979 males and 2481 females, respectively) unrelated she ethnic minority based on a cross-sectional study from Ningde City in Fujian province of China. There were 1692 hypertensives, 1600 prehypertensives and 1168 normotensive controls, respectively. We genotyped 7 variants in CYP17A1, PLEKHA7, CACNB2, ATP2B1, TBX3-TBX5, CSK-ULK3 and SH2B3 reported by the previous GWAs on Europeans. All analyses were performed in an additive genetic model. RESULTS As the minor allele of rs653178 in/near SH2B3 was very rare with the frequency of 0.018, we excluded this single nucleotide polymorphism (SNP) in the further analyses. Of the other 6 loci, linear regression analyses revealed that rs11191548 in CYP17A1 and rs11014166 in CACNB2 were significantly associated with systolic BP (β = -1.17, P = 0.002 and β = -0.50, P = 0.006, respectively), while only SNP rs11191548 was significantly associated with diastolic BP (β = -0.56, P=0.002) after adjusted by age, sex and BMI. Two variants in CACNB2 and PLEKHA7 were found to be significantly related to hypertension (odds ratios [OR] and (95% confidence interval [CI]): 0.79 (0.65-0.97) and 1.19 (1.01-1.41), respectively) in logistic regression analyses after adjusted by age, sex and BMI. In addition, we found that combined risk alleles of the 6 SNPs increased risk of hypertension in a stepwise fashion (P for trend < 0.001). However, none of the 6 SNPs was significantly associated with BMI or prehypertension status. While logistic analysis showed that subjects with cumulative risk alleles more than 9 had significantly higher risk for prehypertension (adjusted OR: 3.10, P < 0.001) compared with those with risk alleles less than 4. CONCLUSIONS We replicated that variations in CYP17A1, CACNB2 and PLEKHA7 were related to BP traits and/or hypertension in She population. In addition, although we failed to observe single gene associated with prehypertension, we first found that conjoint effect of multiple risk alleles on BP might increase the risk of progressing to prehypertension.

Globular adiponectin regulates energy homeostasis through AMP-activated protein kinase–acetyl-CoA carboxylase (AMPK/ACC) pathway in the hypothalamus

Adiponectin is a newly researched adipokine which participates in the regulation of energy homeostasis. AMP-activated protein kinase (AMPK) represents an energy sensor that responds to hormone and nutrition status in vivo and exerts a regulatory effect in the hypothalamus and multiple peripheral tissues. We investigated the possible mechanisms involved in appetite regulation by adiponectin in vitro with GT1-7 cells, a mouse immortalized hypothalamic neuron. The results showed that adiponectin increased the phosphorylation of AMPK, activated AMPK phosphorylated and inactivated acetyl-CoA carboxylase (ACC), and subsequently increased expression of agouti-related peptide (AgRP) mRNA. Our results also indicated that adiponectin had no effect on signal transducer and activator of transcription (STAT3). Together these findings suggest that adiponectin regulated energy homeostasis through the AMPK/ACC pathway but not the JAK/STAT3 pathway in the hypothalamus.

Associations Between Sleep Duration, Daytime Nap Duration, and Osteoporosis Vary by Sex, Menopause, and Sleep Quality

CONTEXT Associations between sleep, daytime nap duration, and osteoporosis remain uncertain, and far less is even known about the influence of sex, menopause, and sleep quality on them. OBJECTIVE The objective of the study was to test the associations between sleep, daytime nap duration, and osteoporosis and whether they vary by sex, menopause, and sleep quality. DESIGN, SETTING, AND PATIENTS This cross-sectional study was based on two communities in China. A total of 8688 participants (3950 males and 4738 females) aged 40 years or older were enrolled in the study. MAIN OUTCOMES MEASURES Self-reported sleep duration, daytime nap duration, sleep quality, and calcaneus bone mineral density were recorded. RESULTS Sleep duration of 8-9 h/d and nap duration of 0 min/d were regarded as reference values. In postmenopausal women, risks (odds ratio and 95% confidence interval) of osteoporosis for sleep durations of 7-8 h/d, 9-10 h/d, and 10 h/d or longer were 1.531 (1.106, 2.121), 1.360 (1.035, 1.787), and 1.569 (1.146, 2.149), respectively (P < .05), and risks of osteoporosis for daytime nap durations of 30-60 min/d and longer than 60 min/d were 1.553 (1.212-1.989) and 1.645 (1.250-2.165), respectively (P < .05). However, a significant difference was not consistently observed in men or premenopausal women, regardless of sleep or daytime nap duration. As for sleep quality, positive results were seen most remarkably in postmenopausal females with good sleep. CONCLUSIONS Sleep durations of 7-8 h/d, 9-10 h/d, and 10 h/d or longer, as well as longer daytime napping times, tend to present higher risks of having osteoporosis, and this tendency is most obvious in postmenopausal women reporting good-quality sleep.

Adiponectin inhibits KISS1 gene transcription through AMPK and specificity protein-1 in the hypothalamic GT1-7 neurons

Adiponectin secreted from adipose tissues plays a role in the regulation of energy homeostasis, food intake, and reproduction in the hypothalamus. We have previously demonstrated that adiponectin significantly inhibited GNRH secretion from GT1-7 hypothalamic GNRH neuron cells. In this study, we further investigated the effect of adiponectin on hypothalamic KISS1 gene transcription, which is the upstream signal of GNRH. We found that globular adiponectin (gAd) or AICAR, an artificial AMPK activator, decreased KISS1 mRNA transcription and promoter activity. Conversely, inhibition of AMPK by Compound C or AMPKα1-SiRNA augmented KISS1 mRNA transcription and promoter activity. Additionally, gAd and AICAR decreased the translocation of specificity protein-1 (SP1) from cytoplasm to nucleus; however, Compound C and AMPKα1-siRNA played an inverse role. Our experiments in vivo demonstrated that the expression of Kiss1 mRNA was stimulated twofold in the Compound C-treated rats and decreased about 60-70% in gAd- or AICAR-treated rats compared with control group. The numbers of kisspeptin immunopositive neurons in the arcuate nucleus region of Sprague Dawley rats mimicked the same trend seen in Kiss1 mRNA levels in animal groups with different treatments. In conclusion, our results provide the first evidence that adiponectin reduces Kiss1 gene transcription in GT1-7 cells through activation of AMPK and subsequently decreased translocation of SP1.

Association study of genetic variants of 17 diabetes-related genes/loci and cardiovascular risk and diabetic nephropathy in the Chinese She population.

Genetic determinations are important in type 2 diabetes (T2DM) pathology. We investigated associations between genetic variants of 17 diabetes‐related genes/loci, T2DM and diabetic complications in Chinese She subjects.

Is Normocalcemic Primary Hyperparathyroidism Harmful or Harmless

CONTEXT Primary hyperparathyroidism (PHPT) is reported to be associated with an increased frequency of hypertension, however, information in this regard is sparse in relation to normocalcemic primary hyperparathyroidism (NPHPT). OBJECTIVE The aim of this study was to determine the association between NPHPT and blood pressure. DESIGN, SETTING, AND PATIENTS We retrospectively enrolled 940 patients who visited the Fujian Provincial Hospital between September 2010 and December 2013 with a measured serum parathyroid hormone (PTH) and calcium level. Among them, 11 patients were diagnosed with NPHPT, while 296 cases with normal PTH and albumin-adjusted serum calcium. MAIN OUTCOMES MEASURES Systolic blood pressure (SBP), diastolic blood pressure (DBP), intact serum PTH, and serum calcium were recorded. RESULTS There were no significant differences between subjects identified with NPHPT and those with normal PTH in terms of age, sex, body mass index, serum calcium, 25-Hydroxyvitamin D, serum creatinine, fasting plasma glucose, triglycerides, total cholesterol, high density lipoprotein, and low density lipoprotein. The subjects with a diagnosis of NPHPT had higher levels of SBP (141.9 ± 20.2 vs 131.2 ± 16.5, P = .041) and DBP (85.2 ± 12.4 vs 76.8 ± 10.3, P = .026) than the subjects in the cohort with normal PTH. After adjustment for all potential confounders, risks (odds ratios and 95% confidence interval) of SBP and DBP in NPHPT patients were 1.035 (1.000, 1.071) and 1.063 (1.004, 1.125), respectively (P < .05). CONCLUSIONS The NPHPT had higher risk of high blood pressure than subjects with normal PTH. It is worth considering the necessity of more aggressive therapeutic intervention aimed to normalize PTH even if patients with NPHPT continue to be normocalcemic.

Association study of genetic variants of 17 diabetes-related genes/loci and cardiovascular risk and diabetic nephropathy in the Chinese She population (中国畲族人群17个糖尿病相关基因位点的遗传变异与心血管风险和糖尿病肾病的相关性)

Genetic determinations are important in type 2 diabetes (T2DM) pathology. We investigated associations between genetic variants of 17 diabetes‐related genes/loci, T2DM and diabetic complications in Chinese She subjects.

Serum Level of Endogenous Secretory Receptor for Advanced Glycation End Products and Other Factors in Type 2 Diabetic Patients With Mild Cognitive Impairment

OBJECTIVE Determine the serum levels of endogenous secretory receptor for advanced glycation end products (esRAGEs) in patients with type 2 diabetes and mild cognitive impairment (MCI) and in control patients with type 2 diabetes but no MCI, and examine the relationship of esRAGE and MCI with other clinical factors. RESEARCH DESIGN AND METHODS A total of 101 patients with type 2 diabetes who were hospitalized in the Department of Endocrinology at Fujian Provincial Hospital between January 2010 and January 2011 were enrolled. There were 58 patients with MCI and 43 patients without MCI (control). Serum levels of esRAGE were measured using an enzyme-linked immunosorbent assay (ELISA). Other clinical parameters were also measured. RESULTS Type 2 diabetic patients with MCI had a longer duration of diabetes; elevated HbA1c, total cholesterol (CHOL), LDL cholesterol (LDL-C), triglyceride (TG), intima-media thickness, C-reactive protein (CRP), and brachial-ankle pulse wave velocity (ba-PWV); and lower ankle brachial index (ABI) and esRAGE relative to the control group. Among patients with MCI, the Montreal Cognitive Assessment (MoCA) score was positively correlated with serum esRAGE but negatively correlated with CHOL. Spearman rank correlation analysis indicated that esRAGE was positively correlated with MoCA score and ABI but negatively correlated with ba-PWV, CHOL, TG, and CRP in all subjects. CONCLUSIONS Our results suggest that esRAGE may be a potential protective factor for dyslipidemia, atherosclerosis, and MCI in patients with type 2 diabetes.

Regulation of GSK-3 beta in the proliferation and apoptosis of human thyrocytes investigated using a GSK-3 beta-targeting RNAi adenovirus expression vector: involvement the Wnt/beta-catenin pathway

Disorders in the proliferation and apoptosis of thyrocytes may induce goitre, adenoma and carcinoma in the thyroid. The Wnt/beta-catenin pathway has been demonstrated to be involved in the regulation of cell proliferation, differentiation and apoptosis in various cell lines. The regulatory mechanism on the proliferation and differentiation of thyrocytes is not well characterized. In the present study, a GSK-3beta-targeting RNA interference (RNAi) adenovirus vector was constructed and delivered to primary human thyrocytes. Results showed that the expression of beta-catenin protein in primary human thyrocytes was increased after GSK-3beta-targeting RNAi adenovirus infection, the proliferation of primary human thyrocytes was significantly stimulated using Bromodeoxyuridine (BrdU) assay, while cell apoptosis was slightly affected which was observed through flow cytometry. It is concluded that the Wnt/beta-catenin pathway plays a significant role in the regulation of the proliferation of primary human thyrocytes.