Search

Background: Aldosterone-producing adenoma (APA) is a benign adrenal tumor with autonomous aldosterone production which causes hypertension and excess cardiovascular risk. Protein phosphorylation regulates aldosterone secretion from adrenal cortical cells, but how signaling networks are remodeled in APA remains unknown. Methods: We performed an integrated proteomic and phosphoproteomic profiling of 15 APA and 10 matched nonfunctioning adrenocortical tumors (NFAT) based on the 4-dimensional label-free technique. We further validated our main findings in enlarged APA samples, mice, and adrenocortical cell line. Results: The proteomic and phosphoproteomic profiling of APA and NFAT quantified 5989 proteins and 9011 phosphopeptides. We highlighted differentially expressed and phosphorylated proteins which modulated aldosterone synthesis and secretion from APA. As intracellular calcium is the central signal for aldosterone synthesis, our integrated calcium signaling network implicated wolframin in the control of calcium influx and CYP11B2 (aldosterone synthase) activation in APA (ratio of wolframin expression in APA to NFAT: 6.411, P Conclusions: Wolframin is a regulatory protein in aldosterone hypersecretion. Remodeled calcium transportation and mitochondrial function are involved in wolframin-related aldosterone secretion.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Neutrophil extracellular traps (NETs) are a network structure composed of loose chromatin and embedded with multiple proteins. Here, we observed increased NETs deposition in the glomeruli of DKD patients and diabetic mice (streptozotocin-induced or db/db mice). After NETs were degraded with DNase I, diabetic mice exhibited attenuated glomerulopathy and glomerular endothelial cells (GECs) injury. We also observed alleviated glomerulopathy and GECs injury in peptidylarginine deiminase 4–knockout mice with streptozotocin-induced diabetes. In vitro, NETs-induced GECs pyroptosis was characterized by pore formation in the cell membrane, dysregulation of multiple genes involved in cell membrane function, and increased expression of pyroptosis-related proteins. Strengthening the GECs surface charge by oleylamine significantly inhibited NETs-induced GECs pyroptosis. These findings suggest that the GECs charge-related pyroptosis is involved in DKD progression, which is promoted by NETs.

Current guidelines recommend adrenal venous sampling (AVS) to identify unilateral primary aldosteronism (UPA) before offering adrenalectomy. However, AVS is costly and technically challenging, limiting its use to expert centres.To establish a model to predict UPA, and therefore, bypass the need for AVS prior to surgery.The model was developed in a Chinese cohort and validated in an Australian cohort. Previously published prediction models of UPA were also tested.primary aldosteronism patients with a definite subtyping diagnosis based on AVS and/or surgery.Diagnostic value of the model.In the development cohort (268 UPA and 88 bilateral primary aldosteronism), combinations of different levels of low serum potassium (≤3.0 or 3.5 mmol/l), high PAC (≥15-30 ng/dl), low PRC (≤2.5-10 μIU/ml) and presence of unilateral nodule on adrenal CT (8-15 mm in diameter) showed specificity of 1.00 and sensitivity of 0.16-0.52. The model of serum potassium 3.5 mmol/l or less, PAC at least 20 ng/dl, PRC 5 μIU/ml or less plus a unilateral nodule at least 10 mm had the highest sensitivity of 0.52 (0.45-0.58) and specificity of 1.00 (0.96-1.00). In the validation cohort (84 UPA and 117 bilateral primary aldosteronism), the sensitivity and specificity of the model were 0.13 (0.07-0.22) and 1.00 (0.97-1.00), respectively. Ten previous models were tested, and only one had a specificity of 1.00 in our cohorts but with a very low sensitivity [0.07 (0.04-0.10) and 0.01 (0.00-0.06) in our development and validation cohorts, respectively].A combination of high PAC, low PRC, low serum potassium and unilateral adrenal nodule could accurately determine primary aldosteronism subtype in 13-52% of patients with UPA and obviate the need for AVS before surgery.

With the widespread use of advanced imaging technology, adrenal tumors are increasingly being identified.To investigate the prevalence and characteristics of adrenal tumors in an unselected screening population in China.Cross-sectional study. (ClinicalTrials.gov: NCT04682938).A health examination center in China.Adults having an annual checkup were invited to be screened for adrenal tumors by adrenal computed tomography.The participants with adrenal tumors had further evaluation for malignancy risk and adrenal function.A total of 25 356 participants were screened, 351 of whom were found to have adrenal tumors, for a prevalence of 1.4%. The prevalence increased with age, from 0.2% in participants aged 18 to 25 years to 3.2% in those older than 65 years. Among 351 participants with adrenal tumors, 337 were diagnosed with an adrenocortical adenoma, 14 with another benign nodule, and none with a malignant mass. In 212 participants with an adenoma who completed endocrine testing, 69.3% were diagnosed with a nonfunctioning adenoma, 18.9% with cortisol autonomy, 11.8% with primary aldosteronism, and none with pheochromocytoma. Proportions of nonfunctioning adenomas were similarly high in various age groups (72.2%, 67.8%, and 72.2% in those aged46, 46 to 65, and ≥66 years, respectively).Only 212 of 337 participants with an adrenocortical adenoma had endocrine testing.The prevalence of adrenal tumors in the general adult screening population is 1.4%, and most of these tumors are nonfunctioning regardless of patient age. Cortisol and aldosterone secretion are the main causes of functional adenomas.National Key Research and Development Program of China and National Natural Science Foundation of China.

Neutrophil-related chronic inflammation (NRCI) may contribute to the pathogenesis of diabetic kidney disease (DKD). We evaluated whether blocking NRCI with low-dose colchicine prevents DKD.A double-blind, randomized, placebo-controlled study was conducted. A total of 160 patients with type 2 diabetes (T2D) and microalbuminuria (urinary albumin creatinine ratio [UACR] 30 to 300 mg/g Cr) who received angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) for at least 3 months were included. Subjects were 1:1 randomized to a placebo or colchicine group (0.5 mg/day).The primary end point was the incidence of overt nephropathy (UACR 300 mg/g Cr). During the 36 months, 38 patients (51.4%) in colchicine group and 39 (54.1%) in the control group developed overt nephropathy (hazard ratio, 1.066; 95% confidence interval, 0.679-1.673; P = .78). Compared with placebo, colchicine modestly lowered levels of NRCI parameters (P values.05 for high-sensitivity C-reactive protein, white blood cell counts, neutrophil counts, and neutrophil-to-lymphocyte ratio), whereas the changes of UACR and estimated glomerular filtration rate (eGFR) were similar between the two groups. There were no significant differences between the two groups in drug-related adverse events, including infection, gastrointestinal symptoms, and limb numbness.In patients with T2D with microalbuminuria, low-dose colchicine effectively and safely lowered NRCI but did not prevent the incidence of overt nephropathy.背景: 中性粒细胞相关性慢性炎症(NRCI)可能与糖尿病肾病(DKD)的发生有关。我们用低剂量秋水仙碱抑制NRCI并评估其是否能延缓DKD的发生。 方法: 本研究为一项双盲、随机、安慰剂对照临床试验。研究共纳入2型糖尿病合并微量白蛋白尿(肌酐比 [UACR] 30-300mg/g Cr)的患者共160名, 所有患者均接受血管紧张素转换酶抑制剂(ACEi)或血管紧张素受体拮抗剂(ARBs)类药物至少3个月。患者按1:1随机分为安慰剂组或秋水仙碱组(接受秋水仙碱0.5mg/d)。 结果: 本研究的主要终点为显著肾病(UACR300mg/g Cr)的发生率。在随访的36个月中, 秋水仙碱组的38名患者(51.4%)以及安慰剂组的39名患者(54.1%)发展成为了显著肾病(危险比1.066; 95%置信区间 0.679-1.673; p=0.78)。秋水仙碱组与安慰剂组相比, NRCI水平有所下降(高灵敏C-反应蛋白、白细胞总数、中性粒细胞总数、中性粒细胞-淋巴细胞比值等指标, 两组有显著性差异, p0.05), 但两组的UACR变化率、估算肾小球滤过率变化率无显著差异。两组的药物相关不良反应, 包括感染、胃肠道症状、肢体麻木等症状无显著差异。 结论: 在2型糖尿病合并微量白蛋白尿的患者中, 低剂量秋水仙碱能有效且安全地降低NRCI, 但是不能延缓DKD的发生。.

Purpose The prevalence of general obesity (commonly defined by body mass index (BMI) in kg/m2) and abdominal obesity (commonly assessed by waist circumference (WC)) has increased rapidly in China. The aim of this study was to investigate the diagnostic accuracy of traditional cut-offs for BMI or WC to identify general or abdominal obesity in Chinese type 2 diabetic patients and propose optimal cut-offs. Patients and Methods BMI and WC were obtained from 1539 type 2 diabetic patients. Body fat percentage and visceral fat area measured by dual-energy x-ray absorptiometry were set as the gold standard to identify general and abdominal obesity. We assessed the diagnostic power of traditional cut-offs for BMI and WC to define obesity, and analyzed receive operating characteristic (ROC) curves to obtain the optimal cut-offs to identify obesity in Chinese type 2 diabetic patients. Results In Chinese type 2 diabetic patients, the optimal BMI was 25 kg/m2 with the best trade-off between sensitivity and specificity (men: 74.6% (95% CI: 70.7-78.2%) and 65.1% (95% CI: 59.7-70.3%), AUC 0.78 (95% CI: 0.75-0.81), p

Context The Endocrine Society Guidelines for the diagnosis of primary aldosteronism (PA) suggest that confirmatory tests (CFT) are not required when the following criteria are met: plasma aldosterone concentration (PAC) is >20 ng/dL, plasma renin is below detection levels, and hypokalemia is present. The evidence for the applicability of the guideline criteria is limited. Objective To develop and validate optimized criteria for sparing CFT in the diagnosis of PA. Design and Setting The optimized criteria were developed in a Chinese cohort using the captopril challenge test, verified by saline infusion test (SIT) and fludrocortisone suppression test (FST), and validated in an Australian cohort. Participants Hypertensive patients who completed PA screening and CFT. Main Outcome Measure Diagnostic value of the optimized criteria. Results In the development cohort (518 PA and 266 non-PA), hypokalemia, PAC, and plasma renin concentration (PRC) were selected as diagnostic indicators by multivariate logistic analyses. The combination of PAC >20 ng/dL plus PRC Conclusions Hypertensive patients with PAC >20 ng/dL, PRC

Objective: To investigate whether serum bisphenol A (BPA) concentration is related to the occurrence of dyslipidemia. Methods: A total of 574 adults were enrolled at baseline and followed up for 5 years. Concentrations of serum BPA, triglycerides (TGs), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured. Dyslipidemia was defined as the existence of one or more of the following conditions: high-LDL-cholesterolemia (LDL ≥140 mg/dL), hypertriglyceridemia (TGs ≥150 mg/dL), or low-HDL-cholesterolemia (HDL

Background A total of 44.7% adults in China have hypertension, but the prevalence of primary aldosteronism (PA) in Chinese hypertensive patients is unknown. Objectives This study prospectively investigated the prevalence, characteristics, and outcomes of PA in newly diagnosed hypertensive patients. Methods In a large community health center, consecutive hypertensive patients with an aldosterone-renin ratio >20 ng/mIU and plasma aldosterone concentration >10 ng/dl underwent captopril challenge test and/or saline infusion test for confirmation of PA. Adrenal computed tomography scan and adrenal vein sampling were used for subtyping. PA patients treated with surgery or medication were followed up for 1 year, and outcomes after treatment were evaluated. Results In total, 1,020 newly diagnosed hypertensive patients were screened over 16 months, of whom 40 were diagnosed with PA, 948 with non-PA, 32 with probable PA, resulting in a prevalence of more than 4.0%. Compared with non-PA, PA patients more frequently displayed microalbuminuria (p = 0.031), but the incidence of cardiovascular events was not different (p = 0.927). For surgically treated patients (n = 7), a complete biochemical success rate was 100% and a complete clinical success rate was 85.7%. For medically treated patients (n = 29), the proportion with optimal blood pressure control was 79%, and among them, 91% (21 of 23) only needed 1 antihypertensive drug: the mineralocorticoid receptor antagonist. Conclusions The prevalence of PA in patients with newly diagnosed hypertension in China was at least 4%. PA screening in newly diagnosed hypertensive patients leads to good clinical outcomes. (Primary Aldosteronism In Hypertensive Patients in China [PA-China]; NCT03155139)

Context The saline infusion test (SIT) is a common confirmatory test for primary aldosteronism (PA). According to the guideline, a postinfusion plasma aldosterone concentration (PAC) of 5-10 ng/dL is considered indeterminate, and recommendations for diagnostic strategies are currently limited in this situation. Objective To explore whether an addition of the captopril challenge test (CCT) could improve the diagnostic accuracy in patients with indeterminate SIT. Methods A total of 280 hypertensive patients with high risk of PA completed this study. Subjects were defined as SIT indeterminate based on their PAC post-SIT. These patients then underwent the CCT where PACs post-CCT >11 ng/dL were considered positive. Using fludrocortisone suppression test (FST) as the reference standard, diagnostic parameters including area under the receiver-operator characteristic curves (AUC), sensitivity and specificity were calculated. Results There were 65 subjects (23.2%) diagnosed as PA indeterminate after SIT. With the addition of CCT, true-positive numbers increased from 134 to 147, and false-negative numbers decreased from 27 to 14. Compared to SIT alone, a combination of SIT and CCT showed a higher AUC (0.91 [0.87,0.94] vs 0.87 [0.83,0.91], P = .041) and an increased sensitivity for the diagnosis of PA (0.91 [0.86,0.95] vs 0.83 [0.76,0.89], P = .028), while the specificity remained similar. In the subgroup with indeterminate SIT results, using PAC post-CCT resulted in a 36% higher AUC than using PAC post-SIT alone for the diagnosis of PA. Conclusion For patients under investigation for possible PA who have indeterminate SIT results, an addition of CCT improves the diagnostic accuracy.

To assess the diagnostic performance of the H-score of 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) in the histopathological diagnosis of adrenocortical tumors (ACT). We retrospectively evaluated 199 cases of ACT, of which 85 were diagnosed as aldosterone-producing adenoma (APA), 66 as cortisol-producing adenoma (CPA), 9 as aldosterone–cortisol co-secreting adenoma, 30 as nonhyperfunctioning adenoma, and 9 as adrenocortical carcinoma (ACC). Immunohistochemical staining was performed using anti-CYP11B1 and anti-CYP11B2 monoclonal antibodies. The staining was quantified by the McCarty’s H-score system. The diagnostic performance was assessed by the receiver operating characteristic curve (ROC). The H-score of CYP11B1 is highest in the CPA group and lowest in the ACC group. The H-score of CYP11B2 in the APA group is significantly higher than other ACT groups. The area under ROC (AUC) of an increased H-score of CYP11B2 (>65) for the diagnosis of APA was 0.971 (95%CI 0.937–0.990). The AUC of an increased H-score of CYP11B1 (>204) for the diagnosis of CPA was 0.725 (95%CI 0.658–0.786). The AUC of a decreased H-score of CYP11B1 (

Bisphenol-A (BPA) is a common environmental pollutant, and exposure to it is associated with proteinuria and may predict the progression of chronic kidney disease; however, the mechanism is not clear. Neutrophil extracellular traps (NETs) are a DNA skeleton coated with various proteases, and it is associated with various types of autoimmune nephritis. In this study, we examine whether NETs is involved in BPA-induced chronic kidney injury. In vivo, BPA exposure resulted in impaired renal function and altered renal morphology, including glomerular mesangial matrix expansion and increased renal interstitial fibroblast markers. Meanwhile, more dsDNA can be detected in the serum, and the NETs-associated proteins, MPO and citH3 were deposited in the renal system. In vitro, BPA and NETs treatment caused podocyte injury, a loss of marker proteins and disorder in the actin skeleton. After NETs inhibition via DNase administration, BPA-induced injuries were significantly relieved. In conclusion, the increase of NETosis in circulation and the renal system during BPA exposure suggests that NETs may be involved in BPA-induced chronic kidney injury.

Objective Saline infusion test (SIT), captopril challenge test (CCT), fludrocortisone suppression test (FST) and oral sodium loading test (SLT) are recommended by the Endocrine Society's Clinical Practice Guidelines to diagnose primary aldosteronism, but which one is the best remains controversial. We aimed to summarize the available comparative data and evaluate the diagnostic accuracy of these four tests. Design We searched PubMed, Embase and the Cochrane Library for relevant studies published between January 1980 and January 2018. Patients Eligible studies reported on the accuracy of one or more of the four confirmatory tests in patients suspected of PA. Measurements Two reviewers independently conducted the data extraction of all selected studies, which consisted of study characteristics and data to estimate the summary receiver operating characteristic (SROC) curve and the corresponding summary area under the curve (SAUC), pooled sensitivity and specificity, diagnostic odds ratios (DOR) with 95% confidence interval (CI). Results We identified 26 articles including 3686 patients. Fifteen articles evaluated the diagnostic accuracy of CCT, 10 of SIT, 1 of FST and none of SLT. For CCT, the SAUC was 0.9207, and the pooled sensitivity and specificity were 0.87 (95% CI: 0.84-0.89) and 0.84 (95% CI: 0.81-0.86), respectively. For SIT, the SAUC was 0.9232, and the pooled sensitivity and specificity were 0.85 (95% CI: 0.82-0.87) and 0.87 (95% CI: 0.85-0.89), respectively. For FST, the pooled sensitivity and specificity were 0.87 (95% CI: 0.66-0.97) and 0.95 (95% CI: 0.82-0.99), respectively. Overall, we found no significant differences in the diagnostic accuracy of CCT and SIT. Conclusions CCT and SIT exhibit high and comparable accuracy for diagnosing PA. CCT may be a more feasible alternative as it is safe and much easier to perform.

Summary Objective The euglycemic‐hyperinsulinemic clamp is the gold standard to evaluate insulin resistance (IR), but there are only a few studies on the prevalence of IR in Chinese Han women with polycystic ovary syndrome (PCOS). This study investigated: (a) the prevalence of IR in Chinese Han women with PCOS by clamp, (b) the degree of reduction in insulin sensitivity (IS) and the contribution of body mass index (BMI). Design Retrospective cross‐sectional analysis. Patients Chinese Han women with PCOS (n = 448) visiting the Department of Endocrinology or the Department of Obstetrics and Gynaecology of the First Affiliated Hospital of Chongqing Medical University. Chinese Han women without PCOS (controls) from the same area (n = 40). Measurements Clamp‐measured IS, age, BMI, and total testosterone. Results The prevalence of IR and reduction in IS were 56.3% and 30.3%, respectively, in Chinese Han women with PCOS (both P 0.05). Conclusions 56.3% of Chinese Han women with PCOS had IR and their reduction in IS was 30.3%. Obesity exacerbated the reduction in IS. When being evaluated by HOMA, the prevalence and the risk factors of IR in Chinese women with PCOS were underestimated.

Objective. It has been increasingly appreciated that G protein-coupled estrogen receptor 1 (GPER1) mediates both proinflammatory and anti-inflammatory response of estrogen. It is also involved in some rapid vascular effects of aldosterone in a mineralocorticoid receptor (MR) independent manner. However, whether GPER1 mediates aldosterone-induced inflammation response in endothelial cells and its relationship with MR are yet undetermined and therefore require further explanation. Method. Based on the hypothesis that GPER1 plays a role in the aldosterone-related vascular inflammation, the present study utilized a model of human umbilical vein endothelial cells transfected with MR siRNA and induced for inflammatory response with increasing concentration of aldosterone. Results. It was discovered that induction of aldosterone had no effect on the expression of GPER1 but promoted the expression of MR. Suppression of MR did not influence GPER1 expression, and GPER1 was capable of mediating part of aldosterone-induced endothelial inflammatory response. This effect may involve phosphoinositide 3-kinases (PI3K) pathway signaling. Conclusion. These findings not only demonstrated the role of GPER1 in aldosterone-induced vascular inflammation but also suggested an alternative for pharmaceutical treatment of hyperaldosteronism considering the unsatisfying effect on cardiovascular risks with MR antagonists.

Perirenal fat is adjacent to kidneys and active in metabolism and adipokine secretion. We aimed to investigate whether perirenal fat is an independent predictor for chronic kidney disease (CKD) and compared it with total, subcutaneous, or visceral fat in patients with diabetes. Perirenal fat thickness (PRFT) was measured by computed tomography, and total body fat (TBF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were assessed by DEXA. In cross-sectional analysis, patients with higher PRFT had a lower estimated glomerular filtration rate (eGFR). Multiple linear regression analysis showed a negative correlation between PRFT and eGFR after confounders adjustment. No association between eGFR and TBF, SAT, or VAT was observed. Longitudinally, 190 patients with type 2 diabetes mellitus (T2DM) without CKD at baseline were followed for 2 years. A total of 29 participants developed CKD. After VAT-based multivariate adjustment, each SD (per-SD) increment in baseline PRFT was associated with a higher incidence of CKD (hazard ratio 1.67, 95% CI 1.04–2.68), while TBF, SAT, and VAT were not. Furthermore, PRFT predicted CKD, with a C-statistic (95% CI) of 0.668 (0.562, 0.774), which was higher than that of TPF [0.535 (0.433, 0.637)], SAT [0.526 (0.434, 0.618)], and VAT [0.602 (0.506, 0.698)]. In conclusion, with perirenal fat there was a higher predictive value for CKD than with total, subcutaneous, or visceral fat in T2DM.

Previous studies revealed that aldosterone-producing adenoma(APA) had a potential for excess co-secretion of cortisol. APA was considered to be composed of heterozygous cell types, including cortisol producing cells(expression of CYP11B1) and aldosterone-producing cells(expression of CYP11B2). The proportion of two cell types and the expression of two steroid synthases showed great heterogeneity in APAs, which may lead to differences in cortisol secretion. However, the hypothesis has not been tested. Therefore, we examined the correlation between tumor size and the ability to autonomously secrete cortisol of APA from the perspective of steroid hormones and immunohistochemistry. 165 patients with surgically proven APA were retrospectively studied. Patients with apparent excess cortisol co-secretion were excluded, which was confirmed by an overnight 1 mg dexamethasone suppression test(1mg-DST). Immunohistochemical staining was performed in 88 tumor specimens and CYP11B2-negative APAs were excluded. The expression of the steroidogenic enzymes was immunohistochemically analyzed, and semi-quantified according to the McCarty H-score system. All APA cases were classified into 2 groups according to the median(15mm) of maximum diameter detected by histological examination: the smaller(n=102) and larger group(n=63). 24am cortisol[78.7(47.7–121.5) VS. 54.6(33.6–81.4) nmol/l, p =0.002] and cortisol after 1mg-DST[28.8(19.1–40.9) VS. 24.1(16.8–30.7) nmol/l, p =0.024] were significantly higher in the larger APA group. The larger APA group had a higher H score of CYP11B1 (p=0.028) and a lower H score of CYP11B2 (p=0.036). Both 24pm cortisol (r =0.2424, p =0.0058)and cortisol after 1mg-DST(r =0.2476, p =0.042)were positively correlated with tumor diameter. The tumor diameter was positively correlated with the H score of CYP11B1 (p=0.0328) and inversely with the H score of CYP11B2(p=0.0285). We tentatively used a new ratio B1 index, calculated by H score of CYP11B1 divided by the sum of H score of CYP11B2 and CYP11B1, to represent the relative expression intensity of CYP11B1 in tumor specimens. B1 index had a stronger correlation with tumor diameter (r =0.3134,p=0.0041). Cortisol after 1mg-DST increased linearly with the tertiles of tumor diameter(p for trend

Aldosterone-producing adenoma (APA) is a main cause of primary aldosteronism (PA). Given that a large benign-appearing unilateral masse (>1 cm in diameter) may represent an aldosterone and cortisol-co-secreting adenoma, dexamethasone suppression testing is required in such patients to exclude or confirm the diagnosis of hypercortisolism. Tuberculosis is highly prevalent in China, and rifamycins are often used in these patients. Rifapentine belongs to the rifamycin family, and we herein for the first time report a case of misdiagnosis of hypercortisolism due to rifapentine use in a patient with APA. Thus, in patients treated with rifapentine, diagnosis of hypercortisolism based on dexamethasone suppression tests can be very misleading.

Introduction Compared with the typical onset of type 2 diabetes in middle age or older, type 2 diabetes with early age of onset has a higher risk of diabetes-related complications. It is unclear whether the early age of diabetes diagnosis would affect the development of end-stage renal disease (ESRD) in patients with diabetic kidney disease (DKD) who are at higher risk of ESRD. Methods We enrolled 1,111 type 2 diabetes patients with DKD in this study. We used the age at diabetes diagnosis of younger than 40 years to define early-onset diabetes and 40 years or older to define late-onset diabetes. Medical history, anthropometry, and laboratory indicators were documented. ESRD was defined by estimated glomerular filtration rate (eGFR) of less than 15 mL/min/1.73 m2 or dialysis. Logistic regression analysis was used to explore the association between early-onset diabetes and ESRD. Results Early-onset diabetes patients had a longer diabetes duration, higher body mass index, and worse blood lipid metabolism profile. Compared with late-onset diabetes patients, patients with early-onset diabetes had a prevalence of ESRD that was twofold higher (9.2% vs 4.3%; P = .009). Univariate analysis showed that early-onset diabetes was a risk factor for ESRD in patients with DKD (P < .05). In multivariate logistic regression analysis, even after adjusting for sex, traditional metabolic factors, drug factors, and diabetes duration, the risk of ESRD in patients with early-onset diabetes was still 3.58-fold higher than in subjects with late-onset (95% CI, 1.47–8.74; P = .005). Conclusions In patients with DKD, early-onset type 2 diabetes is an independent risk factor of ESRD.

Objective: This study aimed to investigate the effect of anti-osteoporosis therapy on plasma aldosterone concentration (PAC), plasma renin concentration (PRC) and the aldosterone/renin ratio (ARR) in patients with postmenopausal osteoporosis. Methods: In 60 patients with postmenopausal osteoporosis, bone mineral density (BMD), PAC and PRC were measured before and after treatment with alendronate (70 mg/week, n=22) or recombinant human parathyroid hormone (20 μg/day, n=35) for 48 weeks. Results: PAC was negatively correlated with the T-score of lumbar spine BMD and femoral neck BMD (lumbar r=−0.386, p37 pg/μIU, and the proportion decreased to 8% (5/57) after treatment. Conclusion: Treatment with alendronate or parathyroid hormone causes decreased PAC and increased PRC, resulting in a decreased ARR in postmenopausal women with osteoporosis.

IntroductionAldosterone is a mediator of progressive renal disease, but the mechanisms for aldosterone-mediated renal impairment in mice with diabetes are not fully defined.MethodsAldosterone and/or mineralocorticoid receptor antagonist eplerenone were used to treat the db/db mice with diabetes. Proximal tubule epithelial cells (PTECs) and fibroblasts were cultured. Blood and kidney samples from patients with diabetes with or without diabetic kidney disease (DKD) were used to verify the findings from animals and cultured cells.ResultsWe found that aldosterone promoted proteinuria and tubulointerstitial extracellular matrix (ECM) accumulation in db/db mice with diabetes while eplerenone mitigated the adverse effect of aldosterone. However, coculture of PTECs and fibroblasts found that when PTECs-derived extracellular vesicles (EVs) were taken up by fibroblasts, ECM production increased remarkably. Moreover, C57BL/6 mice injected with EVs from renal cortex of aldosterone-treated db/db mice showed increased ECM accumulation. Function of the ingredients of PTECs-derived EVs were analyzed, and RNAs were identified to be responsible for the EVs-induced fibroblast dysfunction. Furthermore, microRNA (miRNA) array analysis revealed that miR-196b-5p was the most remarkably increased miRNA in PTECs-derived EVs with aldosterone stimulation. Overexpression of miR-196b-5p in fibroblasts increased ECM production, accompanied by inhibition of the SOCS2 expression and enhanced STAT3 phosphorylation. In addition, plasma levels of miR-196b-5p was higher in patients with DKD as compared with patients without DKD and miR-196b-5p levels positively correlated with the albuminuria concentration. In kidney specimens from patients with diabetes, expression of miR-196b-5p, located mainly in PTECs, increased in patients with DKD as compared with the non-DKD.ConclusionThis study demonstrates the involvement of miR-196b-5p-EVs pathway as a novel mechanism in aldosterone-induced renal fibrosis in diabetes. EVs rich in miR-196b-5p mediate the crosstalk between PTECs and fibroblast during the development of renal fibrosis, which might be associated with STAT3/SOCO2 signaling pathway.

Background The prevalence of primary aldosteronism concurrent with subclinical Cushing’s syndrome was higher than previously thought. Through analyzing a rare clinical case, we summarized the diagnosis and management of primary aldosteronism with subclinical Cushing’s syndrome. Case presentation A 54-year-old Chinese man of Han nationality was diagnosed as having primary aldosteronism with subclinical Cushing’s syndrome. An abdominal computed tomography scan revealed a mass in his left adrenal gland and a mass in his right adrenal gland. After finishing sequential adrenal venous sampling without adrenocorticotropic hormone, the result reminded us that the left and right nodules were responsible for hypercortisolism and aldosterone hypersecretion, respectively. Right and left adrenalectomy were performed successively. The pathological diagnosis was adrenocortical adenoma for both. Histological findings revealed that the right one had positive immunostaining for CYP11B2 and the left one had positive immunostaining for CYP11B1. The immunohistochemistry result helped us to confirm the diagnosis. Somatic KCNJ5 mutation (Leu168Arg) was found in the right tumor; there was no KCNJ5 mutation in the left adrenal tumor. Conclusions We suggest that patients with primary aldosteronism should have a low-dose overnight dexamethasone suppression test to screen for hypercortisolism. It can help avoid misdiagnoses and contribute to proper understanding of the adrenal vein sampling result. Making sure of the nidus of aldosterone and cortisol secretion is crucial for the therapy of patients with primary aldosteronism and subclinical Cushing’s syndrome.

Context More than half of patients diagnosed with unilateral primary aldosteronism (UPA) suffer from persisting hypertension after unilateral adrenalectomy. Objective The objective of this work is to develop and validate a nomogram-based preoperative score (NBPS) to predict clinical outcomes after unilateral adrenalectomy for UPA. Design and Setting The NBPS was developed in an Asian cohort by incorporating predictors independently associated with remission of hypertension after unilateral adrenalectomy for UPA and validated in a Caucasian cohort. Participants Participants comprised patients with UPA achieving complete biochemical success after unilateral adrenalectomy. Main Outcome Measure Measurements included the predictive performance of the NBPS compared with 2 previously developed outcome prediction scores: aldosteronoma resolution score (ARS) and primary aldosteronism surgical outcome (PASO) score. Results Ninety-seven of 150 (64.7%) patients achieved complete clinical success after unilateral adrenalectomy in the training cohort and 57 out of 165 (34.5%) in the validation cohort. A nomogram was established incorporating sex, duration of hypertension, aldosterone-to-renin ratio, and target organ damage. The nomogram showed good C indices and calibration curves both in Asian and Caucasian cohorts. The area under the receiver operating characteristic curve (AUC) of the NBPS for predicting hypertension remission in the training cohort was 0.853 (0.786-0.905), which was superior to the ARS (0.745 [0.667-0.812], P = .019) and PASO score (0.747 [0.670-0.815], P = .012). The AUC of the NBPS in the validation cohort was 0.830 (0.764-0.884), which was higher than the ARS (0.745 [95% CI, 0.672-0.810], P = .045), but not significantly different from the PASO score (0.825 [95% CI, 0.758-0.880], P = .911). Conclusion The NBPS is useful in predicting clinical outcome for UPA patients, especially in the Asian population.

Primary aldosteronism (PA) is notably an independent risk factor for cerebral vascular disease but currently with limited knowledge among young adults. The objectives of the study were to investigate the prevalence of PA in patients under 45 years old with history of acute stroke and the clinical characteristics during stroke attack. We retrieved the medical records of 116 patients once admitted due to acute stroke and cross-sectionally conducted screening test as well as confirmatory test among those patients. An estimated prevalence of PA was 12.7% among all patients and 21.2% among patients combined with hypertension. During stroke attack, PA patients had experienced higher blood pressure as well as decreased potassium level. The average SBP and DBP of PA patients were 180.0 ± 30.9 and 125.9 ± 24.5 mmHg respectively, both remarkably higher than those without PA(mean SBP 148.9 ± 29.6 mmHg, mean DBP94.1 ± 20.5 mmHg). The mean potassium level was 3.13 ± 0.50 vs. 4.01 ± 0.40 mmol/l. The proportion of hypertension and hypokalemia were also increased for PA patients compared with patients without (hypertension 93.3% vs. 51.5%; hypokalemia 80% vs. 8.9%). Patients were equal in National Institutes of Health Stroke Scale (NIHSS) score as well as Glasgow Coma Score (GCS) and stroke subtypes. Considering the fact that excessive aldosterone had detrimental role on cerebral vascular system, we recommend a more rigorous screening for PA with stroke onset under 45 years old, especially those combined with severe hypertension as well as overt hypokalemia.

Plasma aldosterone/renin ratio (ARR) is a useful method for primary aldosteronism (PA) screening. However some confounders, such as medications and dietary, affect plasma renin and aldosterone levels, resulting in false-negative or -positive plasma ARR. This study investigated the association between postmenopausal osteoporosis (PMO) and plasma ARR. Bone mineral density (BMD) was measured by dual-energy X-ray-absorptiometry (DXA) in 324 normotensive postmenopausal women. Based on clinical characteristics and BMD, 186 and 96 subjects were diagnosed as PMO and osteopenia respectively, and the remaining 42 subjects were grouped as normal BMD. Plasma aldosterone concentration (PAC), plasma renin concentration (PRC), parathyroid hormone (PTH), bone alkaline phosphatase (BALP) and 25-Hydroxyvitamin D(25-(OH)D) were determined. Subjects with PMO showed significantly higher levels of PAC (121.0 ± 78.8 vs. 81.8 ± 71.5 pg/ml, p

The diagnosis of primary aldosteronism typically requires at least one confirmatory test. The fludrocortisone suppression test is generally accepted as a reliable confirmatory test, but it is cumbersome. Evidence from accuracy studies of the saline infusion test (SIT) and the captopril challenge test (CCT) has provided conflicting results. This prospective study aimed to evaluate the diagnostic accuracy of the SIT and CCT using fludrocortisone suppression test as the reference standard. One hundred thirty-five patients diagnosed with primary aldosteronism and 101 patients diagnosed with essential hypertension who completed the 3 confirmatory tests were included for the diagnostic accuracy analysis. The areas under the receiver–operator characteristics curves of the CCT and SIT were 0.96 (95% confidence interval [CI], 0.92–0.98) and 0.96 (95% CI, 0.92–0.98), respectively, using post-test plasma aldosterone concentration (PAC) for diagnosis. However, the areas under the receiver–operator characteristics curves of the CCT decreased to 0.71 (95% CI, 0.65–0.77) when the PAC suppression percentage was used to diagnose primary aldosteronism. The optimal cutoff of PAC post-CCT was set at 11 ng/dL, resulting in a sensitivity of 0.90 (95% CI, 0.84–0.95) and a specificity of 0.90 (95% CI, 0.83–0.95), which were not significantly different from those of SIT (with PAC post-SIT set at 8 ng/dL, sensitivity: 0.85 [95% CI, 0.78–0.91], P =0.192; specificity: 0.92 [95% CI, 0.85–0.97], P =0.551). In conclusion, both CCT and SIT are accurate alternatives to the more complex fludrocortisone suppression test. Because CCT is safe and much easier to perform, it may serve as a more feasible alternative. When interpreting the results of CCT, PAC post-CCT is highly recommended.

Summary Background The management of latent Mycobacterium tuberculosis infection is a new priority action for the WHO End Tuberculosis (TB) Strategy. However, national guidelines on latent tuberculosis infection testing and treatment have not yet been developed in China. Here, we present the results from the 2-year follow-up of a study that aimed to track the development of active disease in individuals with latent tuberculosis infection, identify priority populations for latent infection management, and explore the most suitable latent infection diagnostic approach. Methods A population-based multicentre prospective study was done in four sites in rural China, between 2013 and 2015. The baseline survey in 2013 measured the prevalence of latent tuberculosis infection using QuantiFERON-TB Gold In-Tube (QFT) and tuberculin skin test (TST) in eligible participants. During the follow-up phase between 2014–15, we assessed individuals who had tuberculosis infection at baseline (QFT-positivity or TST tuberculin reaction size [induration] of ≥10 mm) for the development of active disease through active case finding. Eligible participants included in follow-up survey had a birth date before June 1, 2008 (5 years or older in 2013), and continuous residence at the study site for 6 months or longer in the past year. Participants with current active tuberculosis at baseline survey were excluded. Findings Between Sept 1, 2013, and Aug 31, 2015, 7505 eligible participants (aged 5 years or older) were included in tuberculosis infection test positive cohorts (4455 were QFT positive, 6404 had TST induration ≥10 mm, and 3354 were positive for both tests) after baseline examination. During the 2-year follow-up period, 84 incident cases of active tuberculosis were diagnosed. Of participants who developed active tuberculosis, 75 were diagnosed with latent infection by QFT, 62 were diagnosed by TST, and 53 were diagnosed by both tests. An incidence rate of 0·87 (95% CI 0·68–1·07) per 100 person-years was observed for individuals who tested positive with QFT, 0·50 (0·38–0·63) per 100 person-years for those who tested positive with TST (p Interpretation Our results suggest that high-risk populations in communities in rural China, such as individuals at a high risk of disease reactivation from previous tuberculosis, should be targeted for latent infection screening and treatment with an interferon-γ releasing assay rather than a TST. Funding National Science and Technology Major Project of China, Program for Changjiang Scholars and Innovative Research Team in University of China, CAMS Innovation Fund for Medical Sciences, and Sanming Project of Medicine in Shenzhen.

Bisphenol A (BPA), one of the most common environmental endocrine disruptors, is considered to promote hepatic lipid deposition. However, the mechanism has not been fully elucidated. The polarization of Kupffer cells (KCs) plays an important role in hepatic inflammation by promoting pro-inflammatory M1 phenotype (M1KCs), which contributes to dysregulated lipid metabolism. The purpose of this study is to investigate the role of KC polarization in BPA-induced hepatosteatosis in male mice. In this study, we examined hepatic lipid contents and quantified M1KC in BPA-treated CD1 mice, and further explored the interaction between KCs and hepatocytes using conditional HepG2 cell culture. BPA treatment significantly increased hepatic fat contents in CD1 mice, accompanied by increased number of pro-inflammatory M1KCs and enhanced secretion of inflammatory cytokines. Increased lipid contents were also observed in HepG2 cells treated with BPA. Interestingly, higher TG contents were observed in HepaG2 cells treated with conditional media from BPA-treated KCs, compared with those treated with BPA directly. Incubation of KCs with BPA promoted the polarization of KCs to pro-inflammatory M1 dominant subtypes, which was blocked by estrogen antagonist ICI182780. Taken together, our results revealed that M1KCs polarization is involved in BPA-induced hepatic fat deposition, which is possibly associated with the estrogen receptor signaling pathway.

The aim of this study was to investigate the association of sarcopenia and diabetic foot disease (DFD) in a cross-sectional study. Body composition was assessed using dual-energy X-ray-absorptiometry (DXA) among 1105 patients with type 2 diabetes (120 patients with newly diagnosed DFD [DFD duration less than 3 months]). Severity of DFD was assessed, referring to foot ulcers, Wagner grade and the percentage of amputation. Skeletal muscle index (SMI) was calculated, and sarcopenia was defined as SMI less than 7.0 kg/m2 (in men) or 5.4 kg/m2 (in women). SMI was significantly decreased in patients with DFD compared to patients without (6.79 ± 1.20 vs. 7.21 ± 1.05 kg/m2, P P P = 0.027) after controlling confounders including age, diabetic duration and diabetic chronic complications. In DFD group, patients with sarcopenia exhibited more foot ulcers, higher Wagner grade and greater percentage of amputation compared to patients without sarcopenia. We conclude that sarcopenia is independently associated with DFD. Worse prognosis is seen in patients with DFD accompanied by sarcopenia.

The association between primary aldosteronism (PA) and obstructive sleep apnea (OSA) has been a matter of debate. 2016 Endocrine Society guideline recommends screening for PA all hypertensive patients with OSA. We designed a multicenter, multiethnic, cross-sectional study to evaluate the prevalence of PA in patients with OSA and the prevalence of OSA in unselected patients with PA. Two hundred and three patients with OSA (102 whites and 101 Chinese) were screened for PA, and 207 patients with PA (104 whites, 100 Chinese, and 3 of African descent) were screened for OSA by cardiorespiratory polygraphy. Eighteen patients with OSA (8.9%) had PA (11.8% of white and 5.9% of Chinese ethnicity). In patients without other indications for PA screening, the prevalence of PA dropped to 1.5%. The prevalence of OSA in patients with PA was 67.6%, consistent in both white and Chinese patients. A correlation between aldosterone levels and apnea/hypopnea index was observed in white patients with PA ( R 2 =0.225, P =0.016) but not in Chinese patients. Multinomial logistic regression confirmed a significant and independent association between plasma aldosterone levels and moderate to severe OSA diagnosis in white patients (odds ratio, 1.002; P =0.002). In conclusion, aldosterone levels may contribute to the severity of OSA in white patients with hyperaldosteronism, but patients with OSA are not at high risk of PA. Results of the present study challenge the current recommendation of the Endocrine Society guideline that all patients with OSA should be screened for PA, irrespective of the grade of hypertension.

Background We conducted a meta-analysis to investigate the association of circulating tumor necrosis factor-1 (TNFR-1) and TNFR-2 with diabetic kidney disease (DKD) progression, which is the first-ever quantitative analysis of these associations thus far. Whether TNFRs were better than albumin-creatinine ratio (ACR) in predicting DKD progression was also explored. Methods A systematic search of the PubMed, EMBASE, and Cochrane Library databases up to 1 February 2018, was conducted. The main outcome was DKD progression, which was defined as eGFR decline, macroalbuminuria, or incidence of DKD-related events. Eligible studies were included for pooled analysis using either fixed-effects or random-effects models to incorporate between-study variation by different measurement standards. Publication bias was evaluated using Egger's test. Results The meta-analysis included 6526 participants from 11 cohorts with circulating TNFR-1 measurements and 5385 participants from 10 prospective studies with circulating TNFR-2 measurements. Compared with the lowest level category, diabetic patients with the highest TNFR-1 or TNFR-2 level category exhibited a higher risk of DKD progression (RR 2.51, 95% CI [1.92-3.27] for TNFR-1; 3.23 [1.99-5.26] for TNFR-2). The risk of DKD progression was also increased with the per unit increment of TNFR-1 or TNFR-2 (1.68 [1.43-1.97] for TNFR-1; 1.69 [1.31-2.17] for TNFR-2). Although existing studies did not support a direct comparison between ACR and TNFRs, it was undeniable that TNFRs could improve the predictive value in DKD progression. Conclusions Circulating TNFR-1 and TNFR-2 are reliable predictors of DKD progression. Whether TNFRs are better than ACR at predicting DKD progression needs to be further investigated.

A 5-year follow-up study found declining disease development rates from latent tuberculosis infection. In the latter 3 years, the incidence, per 100 person-years, was 0.26 for interferon-γ release assay positives and 0.19 for tuberculin skin test positives (P = .28). In addition, all round have been checked.

Background: In primary aldosteronism (PA) patients, the effects of surgery or medication on the risk of cardiovascular diseases (CVD) and all-cause mortality remain controversial. We performed this meta-analysis by integrating previous longitudinal studies to address the issue. Methods: We searched PUBMED, MEDLINE and Cochrane Library for relevant articles until August 31, 2019 for meta-analysis. The inclusion criteria were: patients were diagnosed as PA following standard protocol and received surgery or mineralocorticoid receptor antagonist (MRA) based medical therapies; age-sex matched patients with essential hypertension (EH). Primary endpoints were CVD incidence and all-cause mortality. Findings: For CVD, six studies with 3905 PA and 53733 EH were identified. Compared with EH, treated PA showed a higher risk of CVD (odds ratio [OR] 1⋅79, 95% CI 1⋅39-2⋅31) that was observed in medically treated PA (2⋅11, 1⋅88-2⋅38) and not in surgically treated PA (1⋅51, 0⋅66-3⋅42). For all-cause mortality, four studies with 3708 PA and 54143 EH were identified. Compared with EH patients, the risk of all-cause mortality was significantly lower in treated PA (0⋅86, 0⋅77-0⋅95), due to a lower risk in surgically treated PA (0⋅47, 0⋅34-0⋅66) but not in medically treated PA (0⋅95, 0⋅84-1⋅06). Compared to surgically treated PA, medically treated PA both showed higher risk of CVD and all-cause mortality. Interpretation: Surgically treated PA have a lower risk of CVD compared with medically treated PA, whilst medically treated PA have a higher risk of CVD compared with EH. Surgery significantly reduces the risk of all-cause mortality in PA. Funding Statement: The National Natural Science Foundation of China. Joint Medical Research Project. Outstanding Talents of the First Affiliated Hospital of Chongqing Medical University 2019. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The report was conformed following the Preferred Reporting Items for the Quality of Reporting of Meta-Analyses (PRISMA) checklist.

Objectives: To compare the effect of surgical or medical treatment on the risk of cardiovascular diseases (CVD) and all-cause mortality in patients with established primary aldosteronism (PA). Methods: We searched PUBMED, MEDLINE and Cochrane Library for the meta-analysis. We included patients who were diagnosed with PA following guideline-supported protocols and received surgery or mineralocorticoid receptor antagonist (MRA)-based medical treatment, and age-sex matched patients with treated essential hypertension (EH). Primary endpoints were CVD incidence and all-cause mortality. Results: Compared with EH, patients with treated PA had a higher risk of CVD [odds ratio (OR) 1.79; 95% confidence interval (CI) 1.39–2.31]. This elevated risk was only observed in patients with medically treated PA [OR 2.11; 95%CI 1.88–2.38] but not in those with surgically treated PA. The risk of all-cause mortality was significantly lower in patients with treated PA [OR 0.86; 95% CI 0.77–0.95] compared to EH. The reduced risk was only observed in patients with surgically treated PA [OR 0.47; 95% CI 0.34–0.66], but not in those with medically treated PA. Conclusions: Patients with medically treated PA have a higher risk of CVD compared to patients with EH. Surgical treatment of PA reduces the risk of CVD and all-cause mortality in patients with PA.

The aim of this study is to evaluate the pharmacokinetic and pharmacodynamic (PK-PD) profiles of lispro administered by the QS-M needle-free jet injector in Chinese subjects.A randomized, double-blind, double-dummy, cross-over study was performed. Eighteen healthy volunteers were recruited. Lispro (0.2 units/kg) was administered by the QS-M needle-free jet injector or by conventional pen. Seven-hour euglycemic clamp tests were performed.A larger area under the curve (AUCs) of insulin concentration and glucose infusion rate (GIR) during the first 20 minutes after lispro injection by the jet injector compared to the insulin pen was observed (24.91 ± 15.25 vs. 12.52 ± 7.60 mg. kg(-1), P 0.001 for AUCGIR,0-20 min; 0.36 ± 0.24 vs. 0.10 ± 0.04 U min L(-1), P 0.001 for AUCINS, 0-20 min). Needle-free injection showed a shorter time to reach maximum insulin concentration (37.78 ± 11.14 vs. 80.56 ± 37.18 min, P 0.001) and GIR (73.24 ± 29.89 vs. 116.18 ± 51.89 min, P = 0.006). There were no differences in total insulin exposure and hypoglycemic effects between the two devices.Lispro administered by QS-M needle-free injector results in earlier and higher insulin exposure than conventional pen, and a greater early glucose-lowering effect with similar overall potency.

It has been previously demonstrated that miR-1934 was specially regulated by adiponectin, an anti-inflammatory adipokine, in adipose tissue (AT) in vivo. Herein we investigated the role of miR1934 in the regulation of inflammatory response. Compared with chow-diet fed mice, miR1934 expression was down-regulated in epididymal AT of high-fat diet-induced obese mice. miR1934 expression was down-regulated as well in omental AT of obese subjects in comparison with lean subjects. The circulating miR-1934 was also lower in obese subjects and its levels were correlated negatively with body mass index (BMI), waist circumference (WC), low-density lipoprotein cholesterol (LDL-c), insulin resistance and high-sensitivity C-reactive protein (hs-CRP). The down-regulation of miR1934 in obesity was mimicked by TNF-α treatment of 3T3-L1 adipocytes. Moreover, overexpression of miR1934 suppressed the TNF-α-induced gene expression of interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) in 3T3-L1 adipocytes. De novo formed AT in nude mice transplanted with 3T3-L1 preadipocytes overexpressing miR1934 displayed a reduction in IL-6, TNF-α, IL-1β and an enhancement in IL-10 gene expression when compared with transplant with 3T3-L1 preadipocytes overexpressing miR1934 scrambled control sequence. These results suggest that miR1934 is an important anti-inflammatory factor and may represent a novel mechanism for controlling AT inflammation.

Hypertensive nephropathy is one of the major causes of chronic kidney disease (CKD). Bisphenol A (BPA) is associated with elevated blood pressure and urinary albuminuria. The aim of this study is to evaluate the association between serum BPA with the progression of CKD in patients with primary hypertension.In this prospective study, 302 patients with primary hypertension were followed up for 6 years (195 men and 107 women, 65.29 ± 9.78 years at baseline). The baseline values of serum BPA were measured. Renal function was measured as estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation (eGFRcr-cys). Regression models were used to calculate associations of serum BPA with the annual change in eGFR and the risk of CKD progression.Baseline serum BPA concentration was 0.61(0.26, 2.44) ng/ml and was significantly negatively correlated with the annual change in eGFR (R = -0.197, P 0.001). After adjusting for clinical factors, baseline serum BPA level had a significant negative association with the annual change in eGFR (β = -0.132, P = 0.007). Univariate logistic regression analysis showed that the baseline age, SBP, eGFR, and serum BPA levels were predictors of CKD stage 3 or greater. In multivariate logistic regression analysis, patients with high serum BPA levels exhibited a five-fold increased risk of developing CKD stage 3 or greater compared with patients with low serum BPA levels [odds ratio 4.79 (95% confidence interval 1.81, 14.25), P = 0.004].Serum BPA may be a predictor of CKD progression in patients with primary hypertension.

The relationship between monocyte count and mortality seemed to be varied in different diseases, and it remains unclear in type 2 diabetes (T2D). We conducted a prospective study to investigate whether monocyte count predict all-cause mortality in patients with T2D. In this prospective study, a total of 1073 patients with T2D were enrolled at baseline and 880 patients completed the follow up. The median follow-up time was 47 months. At baseline, clinical characteristics including height, weight, waist circumference, blood pressure were recorded. Biochemical parameters including counts of white blood cells (WBCC), neutrophil (NC) and monocyte (MC), lipid profiles, glycated hemoglobin (HbA1c), serum creatinine were measured. Charlson comorbidity index (CCI) was calculated based on age and comorbidities. Participants were stratified into low, median, and high tertiles according to the baseline MC. Regression models were used to analyze the associations of peripheral MC and the all-cause mortality. Compared to the survived subjects, the baseline MC was significantly higher in patients who deceased during the follow-up (0.45 ± 0.16 vs 0.37 ± 0.15 × 109/L, P = .003). In the multivariate Cox hazard models, subjects in higher MC tertile showed higher risks of all-cause mortality (low tertile as the reference, hazard ratio [HR] 95%CI 2.65 [0.84,8.31] and 3.73 [1.14,12.24] for middle and high MC tertile, respectively) after adjusted for gender, body mass index, CCI, duration of T2D, history of hypertension and metabolic syndrome, drugs, levels of high-sensitivity C-reactive protein, systolic blood pressure, HbA1c, WBCC, and NC. In T2D patients with macro-vascular complications at baseline, 1-SD increment of MC resulted in 1.92-fold higher risk of all-cause mortality. However, the relationship disappeared in subjects without macro-vascular complications at baseline (1.13 [0.72, 1.78], P = .591). Peripheral monocyte count is an independent predictor of all-cause mortality in T2D, especially for subjects with macro-vascular complications.

Objective This study aims to evaluate whether serum Bisphenol A (BPA) is a risk factor for hyperuricemia. Methods In this prospective study, a total of 482 participants without hyperuricemia were enrolled at baseline and followed up for 6 years. Clinical characteristics were recorded, and serum levels of uric acid and BPA were measured. Participants were stratified into tertiles according to low, median, and high baseline serum BPA levels. Regression models were used to analyze associations of serum BPA with the change in uric acid and the risk of developing hyperuricemia. Results At baseline, serum concentrations of BPA was 0.51 (0.24–2.37) ng/mL. After 6 years of follow-up, the change in serum uric acid concentration from baseline to the 6-year mark was significantly higher in subjects with higher baseline BPA concentration (0.03 ± 0.19, 0.07 ± 0.21, and 0.11 ± 0.25 mg/dL for low, median, and high tertiles, respectively, P = 0.006). When adjusted for potential confounders, such as age, renal function, and history of diabetes and hypertension, multivariable logistic analyses showed that subjects in the median or high baseline BPA tertiles exhibited a twofold higher risk of 6-year hyperuricemia incidence compared to subjects in the low baseline BPA tertile [odds ratio (OR) = 2.28 (95% CI: 1.05–4.95) for the median tertile; 2.42 (1.07–5.48) for the high tertile, Pfor Trend = 0.043]. Conclusion In conclusion, serum BPA is an independent risk factor for hyperuricemia.

The relationship between bisphenol A (BPA) and diabetes remains controversial. This study aims to investigate whether serum BPA level could predict the 5-year incidence of type 2 diabetes (T2D).A nested case-control study was performed among Chinese who participated in the environment, inflammation and metabolic diseases study (2008-2013). Of the 3510 subjects who were free of diabetes, 232 subjects developed diabetes during the 5-year follow-up. Cases and controls were matched for age and gender by a ratio of 1:1. Homoeostasis model assessment was used to estimate basal β-cell function (HOMA-β) and insulin resistance (HOMA-IR). Participants were stratified into tertiles based on low, median and high baseline serum BPA levels. Regression models were used to analyze the relationship between serum BPA concentration and the incidence of T2D.At baseline, no significant difference in serum BPA concentration was observed between patients with T2D and controls [1.3 (0.3, 3.7) vs. 1.6 (0.4, 3.9) μmol/L, P = 0.199]; serum BPA concentration was positively associated with fasting plasma glucose (r = 0.27, P 0.001); however, neither HOMA-β nor HOMA-IR correlated with serum BPA concentration. During the follow-up, baseline BPA levels could not predict the 5-year T2D incidence, whether or not adjusted for the potential confounders such as body mass index and blood pressure. [Low BPA tertile was the reference, OR 0.66 (95% CI 0.30, 1.44) for median, OR 0.93 (95% CI 0.41, 2.13) for high.] CONCLUSION: BPA is not associated with a 5-year T2D incidence. These data do not support previous cross-sectional study that BPA exerted a detrimental effect on glucose metabolism.

The prevalence of hyperuricemia has increased rapidly over the past decades. Bisphenol A (BPA) is an environmental endocrine disruptor. We investigated the effects of BPA on uric acid metabolism and its potential mechanisms. Experiments were performed in different animal models, cell cultures, and humans. In 3 different animal models, BPA exposure increased serum and hepatic uric acid with enhanced activity of xanthine oxidase (XO) in liver, whereas the excretion of uric acid was unchanged. Both in vivo and in vitro, BPA-induced uric acid production was decreased after treatment with allopurinol, which is a XO inhibitor. XO led to the accumulation of uric acid after xanthine was added, with the enzyme-catalyzed reaction, which was enhanced by BPA. Altered secondary structures of XO were found by circular dichroism analysis in the conditions of different BPA concentrations. Molecular docking portrayed Asp360 and Lys422 of XO to be the preferred binding sites for BPA. Mutation of both sites significantly blocked the effect of BPA on XO activity. In humans, patients with hyperuricemia exhibited higher levels of serum BPA than subjects without hyperuricemia. These findings demonstrate BPA promotes hyperuricemia by increasing hepatic uric acid synthesis via the activation of XO, probably through direct binding.-Ma, L., Hu, J., Li, J., Yang, Y., Zhang, L., Zou, L., Gao, R., Peng, C., Wang, Y., Luo, T., Xiang, X., Qing, H., Xiao, X., Wu, C., Wang, Z., He, J. C., Li, Q., Yang, S. Bisphenol A promotes hyperuricemia via activating xanthine oxidase.

Background The aim of the present study was to investigate the combined effects of sex hormone-binding globulin (SHBG) and sex hormones on the risk of type 2 diabetes (T2D). Methods A nested case-control study of Chinese participants in the Environment, Inflammation and Metabolic Diseases Study (2008–13) was performed. Of the 3510 subjects free of diabetes, 145 men and 87 women developed diabetes over the 5-year follow-up. One age- and sex-matched control subject was selected for each case. Baseline concentrations of SHBG, estradiol, testosterone, and dehydroepiandrosterone sulfate (DHEA-S) were divided into tertiles and subjects were classified as having low, intermediate and high levels accordingly. Results After multivariate adjustment, men with low SHBG levels had a fourfold greater risk of T2D than men with high SHBG levels. Conversely, men with high estradiol levels had a fourfold greater risk of T2D than men with low estradiol levels. Men with low SHBG + high estradiol had a 20-fold greater risk of T2D than men with high SHBG + low estradiol (odds ratio [OR] 20.23; 95% confidence interval [CI] 4.62–51.33). These risk associations in men were not observed for testosterone or DHEA-S, alone or in combination with SHBG. Compared with low SHBG, the risk of T2D decreased with increasing SHBG tertile (OR 0.92 [95% CI 0.21–4.53], 0.14 [95% CI 0.10–0.74]; Ptrend = 0.043) after multivariate adjustment in women. Estradiol, testosterone, and DHEA-S levels showed no association with T2D in women. Conclusion Low SHBG in conjunction with high estradiol has an additive detrimental effect on the risk of T2D in men.

Aim It is well known that lipid accumulation and inflammation are two important steps in pathogenesis and progress of nonalcoholic fatty liver disease (NAFLD). However, fewer studies have explored the direct relationship between lipid accumulation and inflammation in early NAFLD. Tumor necrosis factor alpha (TNF-α) is one of the classical inflammatory cytokines. AMP-activated protein kinase (AMPK) is known as a critical regulator of energy homeostasis in metabolic processes. This study aims to investigate the role of TNF-α on lipid deposition of HepG2 cells and examine the modification of AMPK pathway. Main methods TNF-α was added in HepG2 cells and lipid accumulation was analyzed by Oil Red O staining and quantitative test of triglyceride (TG). The expressions of phosphorylated AMPK and its pathway (including mTOR and SREBP-1) were determined. Furthermore, an AMPK agonist (metformin or AICAR) or antagonist (compound C) was co-administrated with TNF-α in HepG2 cells to investigate its effect on TNF-α induced lipid deposition. Key findings A significant increment of TG content in HepG2 cells was observed after TNF-α treatment. Meanwhile, substantially suppressed AMPK and ACC phosphorylation, enhanced mTOR and p70S6K phosphorylation, and increased protein expression of FAS and SREBP-1 were found. Co-treatment with metformin or AICAR decreased the TNF-α-induced intracellular TG, accompanied by significantly enhanced AMPK and ACC phosphorylation, suppressed mTOR and p70S6K phosphorylation, and reduced SREBP-1 and FAS expressions. On the contrary, while co-incubated with compound C, AMPK and ACC phosphorylation were suppressed and the inhibitory effect of metformin on HepG2 cell lipid deposition was also attenuated. Significance Our results suggest that TNF-α directly induces lipid accumulation in HepG2 cells, at least in part, through the inhibition of AMPK/mTOR/SREBP-1 pathway.

Background Cross-sectional studies have reported a close association between serum lipopolysaccharide-binding protein (LBP) and many metabolic disorders. However, no longitudinal study has explored the relationship between LBP and type 2 diabetes mellitus (T2DM). The aim of the present study was to investigate the association between serum LBP levels and the risk of developing T2DM. Methods A 5-year nested case-control study of 3510 individuals was performed as part of the Environment, Inflammation and Metabolic Diseases Study (EIMDS). Clinical data were collected at baseline. Serum levels of LBP and other biochemical factors, such as insulin and high-sensitivity C-reactive protein, were detected 5 years later. Subjects were diagnosed as having T2DM on the basis of results of an oral glucose tolerance test (OGTT) and 1998 World Health Organization criteria. Controls were randomly selected to match cases according to age, gender, and body mass index (BMI) in a 1:1 ratio. Odds ratios (OR) for T2DM were calculated using conditional logistic regression analysis. Results Over a 5-year follow-up period, 255 subjects developed T2DM. There was no significant difference in serum LBP levels between the T2DM and control groups at baseline (19.78 ± 6.40 versus 20.53 ± 6.99 μg/mL; P = 0.207). Subjects were divided into three groups based on tertiles of LBP concentrations (n = 170 in each group; T1 = 1.31–17.16 μg/mL LBP; T2 = 17.21–22.37 μg/mL LBP; T3 = 22.49–40.08 μg/mL LBP). There was no significant association between the risk of developing T2DM and any of the LBP tertiles in either a simple model or after adjusting for general status and biochemical factors. Conclusion After matching for gender, age, and BMI, LBP does not improve prediction of the development of T2DM independently.

Summary Background Prophylactic treatment of individuals with latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control in some settings. In China, the prevalence of latent tuberculosis infection, and preventive interventions against this disease, have not been systematically studied. We aimed to assess the prevalence of latent tuberculosis and its associated risk factors in rural populations in China. Methods Between July 1, and Sept 30, 2013, we undertook a baseline survey of a population-based, multicentre, prospective cohort study of registered residents (≥5 years old) at four study sites in rural China. Eligible participants were identified by door-to-door survey with a household sampling design. We screened participants for active tuberculosis and history of tuberculosis then used a tuberculin skin test and an interferon-γ release assay (QuantiFERON [QFT]) to test for latent infection. We used odds ratios (ORs) and 95% CIs to assess variables associated with positivity of QFT and tuberculin skin tests. Findings 21 022 (90%) of 23 483 eligible participants completed a baseline survey. Age-standardised and sex-standardised rates of skin-test positivity (≥10 mm) ranged from 15% to 42%, and QFT positivity rates ranged from 13% to 20%. Rates of positivity for the tuberculin skin test and the QFT test were low in study participants younger than 20 years and gradually increased with age (p for trend Interpretation On the basis of findings showing that the performance of the tuberculin skin test might be affected by various factors including BCG vaccination and age, our results suggest that the prevalence of latent tuberculosis in China might be overestimated by skin tests compared with interferon-γ release assays. Funding The National Science and Technology Major Project of China, the Program for Changjiang Scholars and Innovative Research Team in University of China.