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Open access

Anru Wang, Xueqin Yan, Cai Zhang, Caiqi Du, Wenjun Long, Di Zhan, and Xiaoping Luo

Background

Fibroblast growth factor 1 (FGF1) can regulate glucose and lipid metabolism in obese mice. Serum FGF1 has increased in type 2 diabetes mellitus adults and correlated with BMI. This study aimed to indicate conventional weight loss effects on FGF1 in obese children and adolescents.

Materials and methods

Clinical and metabolic parameters of 88 lean and obese individuals (ages 5–15 years) and 39 obese individuals followed with 6 months of lifestyle intervention were collected. Serum FGF1 levels were detected through enzyme-linked immunosorbent assays.

Results

FGF1 levels were increased in obese individuals. Serum FGF1 levels were significantly correlated with BMI and waist circumferences (r = 0.377, P = 0.012; r = 0.301, P = 0.047, respectively). Multivariate stepwise linear regression analyses showed that FGF1 levels were significantly correlated with HbA1c and HOMA-IR (β = 0.371, P = 0.008; β = 0.323, P = 0.021, respectively). Weight loss (2.3 ± 0.1 kg) was accompanied by a significant reduction of circulating FGF1 levels (7.2 ± 0.4 pg/mL). Changes in FGF1 were significantly correlated with changes in fasting glucose, HOMA-IR and low-density lipoprotein cholesterol (β = 0.277, P = 0.020; β = 0.474, P < 0.001; β = 0.320, P = 0.008, respectively).

Conclusion

FGF1 was related to increased risk of insulin resistance in obese children and adolescents. Serum FGF1 reduced after weight loss in obese individuals and was associated with the improvement of insulin resistance. Changes in serum FGF1 were more correlated with insulin resistance than changes in obesity per se.

Open access

Changjiao Yan, Meiling Huang, Xin Li, Ting Wang, and Rui Ling

Objective

To investigate the mutant status of BRAF gene and analyze its relationship to epidemiological risk factors and clinical outcomes among patients with papillary thyroid cancer (PTC) in the largest, single-institution Chinese cohort to date.

Methods

The medical records of 2048 PTC patients were reviewed in this retrospective study. Single-factor and multiple logistic regression analyses were applied to identify risk factors for BRAF V600E mutation. Survival outcomes including distant metastatic and persistent or recurrent PTC were examined, with a mean follow-up time of 23.4 (5–47) months.

Results

The BRAF V600E mutation was present in 83.7% of patients (1715 of 2048). Correlation was found between BRAF V600E mutation and several epidemiological features, including age, concomitant hypertension and Hashimoto thyroiditis (HT). For the clinicopathological features, BRAF V600E was significantly associated with bilateral multifocality (odds ratio (OR) 1.233, 95% confidence interval (CI) 1.063–1.431, P < 0.01) and less lateral lymph node metastases (OR 0.496, 95% CI 0.357–0.689, P < 0.01). Smaller tumor size and advanced disease stage were significant in single-factor analyses but became insignificant after multivariate adjustment. No association was found between BRAF V600E mutation and extrathyroidal invasion, distant metastatic and disease persistence or recurrence.

Conclusion

Part of epidemiological features are independent risk or protective factors for BRAF V600E mutation. The presence of BRAF V600E mutation is not an aggressive prognosis on poor clinical outcomes in PTC. However, the high prevalence of BRAF V600E may provide guidance for surgery strategy and opportunity for targeted treatment in recurrent and advanced stage disease.

Open access

Chun-feng Lu, Wang-shu Liu, Xiao-qin Ge, Feng Xu, Jian-bin Su, Xue-qin Wang, and Yan Wang

Background

Adenosine deaminase (ADA) is essential for the differentiation and maturation of lymphocytes, while lymphocytes infiltration in thyroid tissue is a vital pathological feature of Graves’ disease (GD). The aim of the present study was to compare the concentration of ADA between healthy controls (HC) and patients with GD, and evaluate the association between ADA and GD.

Methods

A total of 112 GD patients and 77 matched HC were enrolled in this study. Each participant was examined for thyroid hormones and autoantibodies, ADA concentration, and thyroid ultrasonography.

Results

Serum ADA levels in GD patients were significantly higher than that in HC subgroup (P < 0.001). In GD patients, serum ADA levels were positively associated with serum-free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb) levels, and total thyroid gland volume (thyroid VolT) and negatively associated with serum thyroid-stimulating hormone receptor (TSH) levels (all P < 0.05). There were no similar correlations in the HC subgroup. Multiple linear regression analysis suggested that serum TSH, FT3, and ADA levels played an important role in serum TRAb levels.

Conclusions

Our results demonstrated that serum ADA levels were closely associated with GD.

Open access

Hui Long, Yanhong Nie, Li Wang, Yong Lu, Yan Wang, Yijun Cai, Zhen Liu, Miaomiao Jia, Qifeng Lyu, Yanping Kuang, and Qiang Sun

AMH as a promising predictor of ovarian response has been studied extensively in women undergoing assisted reproductive technology treatment, but little is known about its prediction value in monkeys undergoing ovarian stimulation. In the current study, a total of 380 cynomolgus monkeys ranging from 5 to 12 years received 699 ovarian stimulation cycles. Serum samples were collected for AMH measure with enzyme-linked immunosorbent assay. It was found that serum AMH levels were positive correlated with the number of retrieved oocytes (P < 0.01) in the first, second and third stimulation cycles. In the first cycles, area under the curve (ROCAUC) of AMH is 0.688 for low response and 0.612 for high response respectively, indicating the significant prediction values (P = 0.000 and P = 0.005). The optimal AMH cutoff value was 9.68 ng/mL for low ovarian response and 15.88 ng/mL for high ovarian response prediction. In the second stimulation cycles, the significance of ROCAUC of AMH for high response rather than the low response was observed (P = 0.001 and P = 0.468). The optimal AMH cutoff value for high ovarian response was 15.61 ng/mL. In the third stimulation cycles, AMH lost the prediction value with no significant ROCAUC. Our data demonstrated that AMH, not age, is a cycle-dependent predictor for ovarian response in form of oocyte yields, which would promote the application of AMH in assisted reproductive treatment (ART) of female cynomolgus monkeys. AMH evaluation would optimize candidate selection for ART and individualize the ovarian stimulation strategies, and consequentially improve the efficiency in monkeys.

Open access

Jingci Chen, Yan Wu, Pengyan Wang, Huanwen Wu, Anli Tong, and Xiaoyan Chang

Introduction

Composite pheochromocytoma/paraganglioma (CP) is a rare neoplasm with most cases presented as single reports. Little is known about its pathogenesis and relationship with ordinary pheochromocytoma (PCC) or paraganglioma (PGL). Our study is aimed at analyzing the status of SDH and ATRX and identifying novel genetic changes in CP.

Methods

Eighteen CP cases were collected. SDH and ATRX status was screened by immunohistochemistry. Targeted region sequencing (TRS) was successfully performed on formalin-fixed paraffin-embedded tissues in two cases within 3 years. Based on the TRS result, Sanger sequencing of BRAF and HRAS was performed in fifteen cases (including the two cases with TRS performed), with three cases excluded due to the limited amount of tissue.

Results

Histopathologically, all the cases were composite PCC/PGL-ganglioneuroma (GN). The GN components were either closely admixed or juxtaposed with the PCC/PGL components, with a highly variable percentage (10–80%). All cases stained positive for SDHB and ATRX. HRAS and BRAF mutations were identified during TRS. In the subsequent Sanger sequencing, 20.0% (3/15) harbored BRAF mutations (K601E and K601N) and 46.7% (7/15) harbored HRAS mutations (Q61R, Q61L, G13R). The mutation rates were both significantly higher than reported in ordinary PCC/PGL.

Conclusions

We demonstrated that composite PCC/PGL-GN might be a unique entity with frequent HRAS and BRAF mutations rather than genetic changes of SDH and ATRX. Our findings revealed the possible pathogenesis of composite PCC/PGL-GN and provided clues for potential treatment targets.

Open access

Chun-feng Lu, Xiao-qin Ge, Yan Wang, Jian-bin Su, Xue-qin Wang, Dong-mei Zhang, Feng Xu, Wang-shu Liu, and Min Su

Background

Prolonged heart rate-corrected QT (QTc) interval may reflect poor prognosis of patients with type 2 diabetes (T2D). Serum adenosine deaminase (ADA) levels are related to hyperglycemia, insulin resistance (IR) and inflammation, which may participate in diabetic complications. We investigated the association of serum ADA levels with prolonged QTc interval in a large-scale sample of patients with T2D.

Methods

In this cross-sectional study, a total of 492 patients with T2D were recruited. Serum ADA levels were determined by venous blood during fasting. QTc interval was estimated from resting 12-lead ECGs, and prolonged QTc interval was defined as QTc > 440 ms.

Results

In this study, the prevalence of prolonged QTc interval was 22.8%. Serum ADA levels were positively associated with QTc interval (r = 0.324, P < 0.0001). The proportion of participants with prolonged QTc interval increased significantly from 9.2% in the first tertile (T1) to 24.7% in the second tertile (T2) and 39.0% in the third tertile (T3) of ADA (P for trend < 0.001). After adjusting for other possible risk factors by multiple linear regression analysis, serum ADA level was still significantly associated with QTc interval (β = 0.217, t = 3.400, P < 0.01). Multivariate logistic regression analysis showed that female (OR 5.084, CI 2.379–10.864, P < 0.001), insulin-sensitizers treatment (OR 4.229, CI 1.290–13.860, P = 0.017) and ADA (OR 1.212, CI 1.094–1.343, P < 0.001) were independent contributors to prolonged QTc interval.

Conclusions

Serum ADA levels were independently associated with prolonged QTc interval in patients with T2D.

Open access

Zi-Di Xu, Wei Zhang, Min Liu, Huan-Min Wang, Pei-Pei Hui, Xue-Jun Liang, Jie Yan, Yu-Jun Wu, Yan-Mei Sang, Cheng Zhu, and Gui-Chen Ni

This study aims to summarize and analyze the clinical manifestations, genetic characteristics, treatment modalities and long-term prognosis of congenital hyperinsulinemia (CHI) in Chinese children. Sixty children with CHI, who were treated at Beijing Children’s Hospital from January 2014 to August 2017, and their families, were selected as subjects. The CHI-related causative genes in children were sequenced and analyzed using second-generation sequencing technology. Furthermore, the genetic pathogenesis and clinical characteristics of Chinese children with CHI were explored. Among the 60 CHI children, 27 children (27/60, 45%) carried known CHI-related gene mutations: 16 children (26.7%) carried ABCC8 gene mutations, seven children (11.7%) carried GLUD1 gene mutations, one child carried GCK gene mutations, two children carried HNF4α gene mutations and one child carried HADH gene mutations. In these 60 patients, eight patients underwent 18F-L-DOPA PET scan for the pancreas, and five children were found to be focal type. The treatment of diazoxide was ineffective in these five patients, and hypoglycemia could be controlled after receiving partial pancreatectomy. In conclusion, ABCC8 gene mutation is the most common cause of CHI in Chinese children. The early genetic analysis of children’s families has an important guiding significance for treatment planning and prognosis assessment.

Open access

Jun-Xin Yan, Bin-Jing Pan, Ping-Ping Zhao, Li-Ting Wang, Jing-Fang Liu, and Song-Bo Fu

Objective

Previous studies have shown the correlations between serum ferritin and non-alcoholic fatty liver disease (NAFLD) or diabetes. However, this relationship remains unclear in patients with type 2 diabetes (T2DM) with NAFLD. Therefore, this study aimed to elaborate the relationship between serum ferritin levels and NAFLD in middle-aged and older patients with T2DM and further explored the biomarkers for NAFLD in T2DM.

Methods

A total of 805 middle-aged and older patients with T2DM were divided into NAFLD and non-NAFLD groups, and their serum ferritin levels were compared. Next, NAFLD group were divided into five subgroups according to the quintile levels of serum ferritin, and the differences in the constituent ratios of NAFLD were analyzed. A logistic regression analysis was performed to determine the risk factors for NAFLD in patients with T2DM.

Results

The serum ferritin levels were significantly higher in T2DM patients with NAFLD (168.47 (103.78, 248.00) ng/mL) than in the non-NAFLD patients (121.19 (76.97, 208.39) ng/mL). The constituent ratios of NAFLD were significantly higher in the F5 and F4 groups than in the F2 or F1 groups (22.70 and 22.70% vs. 15.90 and 16.90%, respectively; P < 0.05). Binary logistic regression analysis showed that serum ferritin (P = 0.001) was an independent risk factor for NAFLD in patients with T2DM.

Conclusions

Serum ferritin levels were significantly increased in T2DM with NAFLD, and the constituent ratios of NAFLD increased gradually along with the increased levels of serum ferritin. Thus, serum ferritin is an independent risk factor for NAFLD in patients with T2DM.

Open access

Lang Qin, Xiaoming Zhu, Xiaoxia Liu, Meifang Zeng, Ran Tao, Yan Zhuang, Yiting Zhou, Zhaoyun Zhang, Yehong Yang, Yiming Li, Yongfei Wang, and Hongying Ye

Introduction

The purpose of the study was to describe lipid profile and explore pathogenetic role of LDL-c on hypertension in patients with Cushing’s disease (CD). Hypertension is a common feature in patients with CD. Previous study found low-density lipoprotein cholesterol (LDL-c) uptake in vascular cells might be involved in vascular remodeling in patients with CD. Therefore, we evaluated the relationship between lipid profile and the blood pressure in patients with CD.

Methods

This retrospective study included 84 patients referred to Huashan Hospital for the evaluation and diagnosis of CD from January 2012 to December 2013. All subjects had detailed clinical evaluation by the same group of endocrinology specialists to avoid subjective influences.

Results

We found that high LDL-c patients had significant higher body mass index (BMI), systolic blood pressure (SBP), cholesterol (CHO), triglyceride (TG), and apolipoproteinB (apoB) (P < 0.05). An association was detected between SBP values and lipids profile including CHO, TG, LDL-c, apolipoproteinA (apoA), apoB and lipoprotein(a) (LP(a)). After adjustment for all covariates, the LDL-c remained positively associated with SBP. In patients with or without taking statins, patients with LDL-c ≥3.37 mmol/L had higher SBP than patients with LDL-c <3.37 mmol/L. Then, LDL-c was coded using restricted cubic splines (RCS) function with three knots located at the 5th, 50th and 95th percentiles of the distribution of LDL-c. Compared to individuals with 3.215 mmol/L of LDL-c, individuals with 4.0, 4.5 and 5.0 mmol/L of LDL-c had differences of 3.86, 8.53 and 14.11 mmHg in SBP, respectively.

Conclusions

An independent association between LDL-c and SBP was found in patients with CD. We speculate that LDL-c may be a pathogenic factor for hypertension in those patients.

Open access

Lianghui You, Yan Wang, Yao Gao, Xingyun Wang, Xianwei Cui, Yanyan Zhang, Lingxia Pang, Chenbo Ji, Xirong Guo, and Xia Chi

Enhanced brown adipose tissue (BAT) mass and activity have been demonstrated to promote the expenditure of excess stored energy and reduce prevalence of obesity. Cold is known as a potent stimulator of BAT and activates BAT primarily through the β3-adrenergic-cAMP signaling. Here, we performed RNA-sequencing to identify differential miRNAs in mouse BAT upon cold exposure and a total of 20 miRNAs were validated. With the treatment of CL-316,243 (CL) and forskolin (Fsk) in mouse and human differentiated brown adipocyte cells in vitro, miR-23b-5p, miR-133a-3p, miR-135-5p, miR-491-5p, and miR-150-3p expression decreased and miR-455-5p expression increased. Among these deferentially expressed miRNAs, miR-23b-5p expression was differentially regulated in activated and aging mouse BAT and negatively correlated with Ucp1 expression. Overexpression of miR-23b-5p in the precursor cells from BAT revealed no significant effects on lipid accumulation, but diminished mitochondrial function and decreased expression of BAT specific markers. Though luciferase reporter assays did not confirm the positive association of miR-23b-5p with the 3′UTRs of the predicted target Ern1, miR-23b-5p overexpression may affect brown adipocyte thermogenic capacity mainly through regulating genes expression involving in lipolysis and fatty acid β-oxidation pathways. Our results suggest that miRNAs are involved in cold-mediated BAT thermogenic activation and further acknowledged miR-23b-5p as a negative regulator in controlling thermogenic programs, further providing potential molecular therapeutic targets to increase surplus energy and treat obesity.