1.Therapeutic analysis of unilateral adrenalectomy for Cushing syndrome in patients with adrenocorticotropic hormone independent bilateral macronodular adrenal hyperplasia
Baojun WANG ; Xintao LI ; Lu TANG ; Wenzheng CHEN ; Yu GAO ; Jinzhi OUYANG ; Xu ZHANG
Chinese Journal of Urology 2017;38(4):260-263
Objective To investigate the therapeutic outcomes of unilateral adrenalectomy for Cushing syndrome in patients with adrenocorticotropic hormone (ACTH) independent bilateral macronodular adrenal hyperplasia.Methods 22 patients diagnosed with Cushing syndrome caused by ACTH independent bilateral macronodular adrenal hyperplasia from January 2005 to December 2015 were retrospectively concluded.There are 17 male patients and 5 female patients with the median age of 46.5 years.All patients were presented with Cushing syndrome such as moon face, buffalo hump and other typical symptoms of Cushing syndrome.The laboratory tests showed disappearance of cortisol rhythm, elevated 24-hour urinary free cortisol, suppressed or normal ACTH and unsuppressed low dose dexamethasone suppressing test.CT scan showed bilateral macronodular adrenal hyperplasia in all patients.Results All the patients received unilateral adrenalectomy.Pathological results showed adrenal cortex nodular hyperplasia.16 patients had reexamination in the endocrine department.The median follow-up time was 26 (17-118)months for these 16 patients.In the follow-up between 3 to 9 months after surgery, laboratory test showed serum and urinary cortisol level returned to normal range and Cushing syndrome also disappeared in these 16 patients.CT scan showed no recurrence.And no adrenal insufficiency occurred.One patient had recurrence one year after surgery and two patients turned better after surgery but had recurrence at 3 years and 10 years after surgery.Two patients received contralateral adrenalectomy and cortisol hormone replacement therapy after surgery.Another patient with recurrence refused second surgery.No recurrence was observed in other patients.Four patients were followed up by telephone, and all recovered well after surgery.18 patients had hypertension before surgery and their blood pressure significantly decreased after surgery.Among them 13 cases blood pressure returned to normal range.5 patients had elevated blood glucose before surgery, and 3 patients' blood glucose returned to normal range.Conclusions Unilateral adrenalectomy for Cushing syndrome in patients with ACTH independent bilateral macronodular adrenal hyperplasia is safe and effective.
2.The influencing factors on the height of patients with pituitary stalk interruption syndrome
Dan WU ; Yiming MU ; Jinzhi OUYANG ; Lijuan YANG ; Guoqing YANG ; Jianming BA ; Jingtao DOU
Chinese Journal of Endocrinology and Metabolism 2013;29(11):959-961
Thirty cases of pituitary stalk interruption syndrome were divided into normal height (group 1) and short stature (group 2).There was no significant difference in growth hormone or insulin-like growth factor-Ⅰ levels between two groups(P>0.05).Expected height and body mass index in group 1 were higher than those in group 2,while testosterone,cortisol,and FT4 were lower.Height were positively correlated with age,expected height,birth weight,and body mass index.The height of patients with pituitary stalk interruption syndrome depended on both genetic factors and the hormones from pituitary-target gland.
3.Effect and significance of steroidogenic factor-1 gene silencing on proliferation of human adrenocortical H295R cells
Dongliang HU ; Jinzhi OUYANG ; Xin MA ; Hongzhao LI ; Baojun WANG ; Taoping SHI ; Shaogang WANG ; Xu ZHANG
Chinese Journal of Urology 2010;31(8):524-528
Objective To study the influence of inhibited steroidogenic factor-1 on human adrenocortical H295R cells, and explore its role in the pathogenesis of adrenal tumors. Methods The plasmids pGenesil1-SF-1-shRNA which containing U6 promoter and SF-1-specific short hairpin RNA (shRNA) and pGenesil1-negative-shRNA containing unspecific shRNA were transfected into H295R cell. The expression of SF-1 was measured by Western blot and real-time polymerase chain reaction(RT-PCR). Cell proliferation was analyzed by WST-1 assay and cell count. Ki-67 expression was detected by immunohistochemistry and cell apoptosis was examined by TUNEL assay. Results Compared with those in control cells, the protein and mRNA level of SF-1- transfected cells were reduced by 69.7% and 71.2% (P<0. 01). WST-1 and cell count method showed that SF-1 gene silencing obviously inhibited cell proliferation(P<0. 01). By contrast, there was a 3. 7-fold increase in the percentage of apoptotic H295R cells in SF-1-inhibited group than that of control group (P<0. 01). Immunohistochemistry showed that Ki-67 positive cells in SF-1-inhibited cells were lower than the negative control cells (16.90±2.17) % and (33. 48±3.16)%,(P<0. 01). Conclusion SF-1 gene silencing can inhibit the proliferation of adrenocortical cells, and it is expected to become a key protein in understanding pathogenesis of adrenal tumors or treating them.
4.Expression of angiotensin II receptors in aldosterone-producing adenoma of the adrenal gland and their clinical significance.
Zhun, WU ; Dong, NI ; Yongji, YAN ; Jun, LI ; Baojun, WANG ; Jinzhi, OUYANG ; Guoxi, ZHANG ; Xin, MA ; Hongzhao, LI ; Xu, ZHANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2010;30(4):486-9
The expression of angiotensin II type 1 receptor (AT(1)R) and angiotensin II type 2 receptor (AT(2)R) in aldosterone-producing adenoma (APA) of the adrenal gland was detected, and their relationship with clinical indexes of APA was analyzed. The mRNA expression of AT(1)R and AT(2)R in 50 cases of APA and tissues adjacent to tumors and 12 cases of normal adrenal tissues was detected by using reverse transcriptase polymerase chain reaction (RT-PCR). The expression of AT(1)R and AT(2)R proteins in paraffin-embedded slices of tissue was detected by immunohistochemistry. The expression of AT(1)R in adenoma, tissues adjacent to tumor, and normal tissues of the adrenal gland showed no significant differences. The expression of AT(2)R in APA tissue was lower than that in normal adrenal gland tissues (P<0.05). Correlation analysis of the mRNA expression level of AT(2)R and clinical data from patients demonstrated that AT(2)R expression was negatively related to plasma aldosterone concentration (PAC) (r=-0.467, P<0.05), but positively related with plasma renin activity (PRA) (r=0.604, P<0.05). It is concluded that down-regulation of the AT(2)R expression is possibly related with the tumorigenesis of APA.
5.Association of polymorphisms in angiotensin II receptor genes with aldosterone-producing adenoma.
Jinzhi, OUYANG ; Zhun, WU ; Jinchun, XING ; Yongji, YAN ; Guoxi, ZHANG ; Baojun, WANG ; Hongzhao, LI ; Xin, MA ; Xu, ZHANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2011;31(3):301-5
This study examined the association of polymorphisms in angiotensin II receptor genes (AT (1) R and AT (2) R) with the risk for aldosterone-producing adenoma (APA) in a Chinese Han population. Four polymorphisms including rs5182 (573T/C) in exon 4, rs5186 (1166A/C) in 3'-untranslated region (3'-UTR) in AT (1) R gene and rs5194 (2274G/A) in 3'-UTR, rs1403543 (1675G/A) in intron 1 in AT (2) R gene were detected in 148 APA patients and 192 normal subjects (serving as control) by using a MGB-Taqman probe. The distribution of genotypes of each locus was in accordance with Hardy-Weinberg Equilibrium (HWE) in the APA and control groups (P>0.05). The allele A frequency at rs5194 was significantly higher in the APA group (0.49) than in the control group (0.35) (χ (2)=12.08, P=0.001). Subjects with homozygotic genotype AA and heterozygotic genotype GA were at an increased risk for APA as compared to those with GG genotype (OR=2.66, 95% CI=1.45-4.87; OR=1.67, 95% CI=1.02-2.74). Furthermore, rs5194 single-nucleotide polymorphism (SNP) at AT (2) R gene was significantly associated with APA in additive (OR=1.64, 95% CI=1.21-2.20, P=0.001), dominant (OR=1.94, 95% CI=1.23-3.06, P=0.003), and recessive model (OR=2.01, 95% CI=1.17-3.45, P=0.01). It was concluded that rs5194 polymorphism at AT (2) R gene was associated with the risk for APA, which may constitute a genetic marker of APA.
6.Inhibitory effects of microRNA-34a on cell migration and invasion of invasive urothelial bladder carcinoma by targeting notch1.
Chao, ZHANG ; Zhiyong, YAO ; Mingyang, ZHU ; Xin, MA ; Taoping, SHI ; Hongzhao, LI ; Baojun, WANG ; Jinzhi, OUYANG ; Xu, ZHANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2012;32(3):375-82
MicroRNAs (miRNAs or miRs) are a class of short, non-coding RNAs that participate in various oncological processes. This study aims to explore the roles of microRNA-34a (miR-34a) in invasive urothelial bladder carcinoma. miR-34a was transfected into bladder cancer cell lines 253J and J82. The miR-34a expression levels in tissues and cells were detected by using qRT-PCR. The Notch1 expression was detected by qRT-PCR and Western blotting. Cell migratory and invasive abilities were measured by Transwell chamber assay. Bioinformatics and luciferase assay were performed to predict and analyze the binding sites between miRNA-34a and Notch1. It was found that there was aberrant expression of miR-34a in bladder cancer tissues. Moreover, we revealed that ectopic expression of miR-34a suppressed cell migration and invasion, while forced expression of Notch1 increased cell migratory and invasive abilities. Finally, we observed that miR-34a transfection significantly down-regulated luciferase activity and reduced the mRNA and protein levels of Notch1. Our study concluded that microRNA-34a antagonizes Notch1 and inhibits cell migration and invasion of bladder cancer cells, which indicates the tumor-suppressive function of microRNA-34a in bladder cancer.
7.Association of polymorphisms in aldosterone synthase and 11 beta-hydroxylase genes with the risk of primary aldosteronism
Guoxi ZHANG ; Jinzhi OUYANG ; Baojun WANG ; Xiyuan DENG ; Chao WANG ; Taoping SHI ; Zhenghua JU ; Hua XU ; Xin MA ; Hongzhao LI ; Zhun WU ; Shuanglin LIU ; Xu ZHANG
Chinese Journal of Urology 2009;30(3):176-180
Objective To determine the association of mutations in aldosterone synthase (CYPllB2)and 11 beta-hydroxylase(CYP11B1)genes with primary aldosteronism(PA).Methods Five mutations of CYP11B2 and CYP11B1 genes were analyzed in patients with PA and normal population.Among them,intron 2 was detected by 2 independent PCR reactions,and the others were analyzed using Taqman probes.The Haploview 4.0,SNPassoc 1.5-3 and Haplo.stats 1.3.8 were used to analyse the association between polymorphisms and PA.Results All the selected mutations were successfully genetyped.Only rs64lO allelic frequencies in patients with aldosterone-producing adenoma (APA)and idiopathic hyperaldosteronism(IHA)were significantly different with those in controls (P<0.05).There was a relative excess of AA homozygotes and AG heterozygotes of rs6410 allele in APA group compared with control group(P<0.01).There were significantly different genotypes AA and AG of rs6410 allele between patients with IHA and controls only after adjusted for age,gender,eeptible haplotype AAAWT was identified to be significantly associated with APA(OR=1.44,95%CI 1.19-1.76).Three susceptible haplotypes AAAWT,AGGWT and AGAWC were identified to be significantly associated with IHA(OR=1.55,95%CI 1.23-1.96;OR=1.49,95%CI 1.17-1.89;OR=1.40,95%CI 1.04-1.88).In contrast,1 protective haplotype GGAWT showed significant difference between patients with APA and controls(OR=0.73,95%CI 0.55-0.97).Conclusion There is a significant association between genetic variations in CYP11B2 and CYP11B1 genes and genetie predisposition to PA.
8.Aortic cell apoptosis in rat primary aldosteronism model.
Yongji, YAN ; Jinzhi, OUYANG ; Chao, WANG ; Zhun, WU ; Xin, MA ; Hongzhao, LI ; Hua, XU ; Zheng, HU ; Jun, LI ; Baojun, WANG ; Taoping, SHI ; Daojing, GONG ; Dong, NI ; Xu, ZHANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2010;30(3):385-90
This study aimed to determine whether aldosterone could induce vascular cell apoptosis in vivo. Thirty-two male rats were randomly divided into 4 groups: vehicle (control), aldosterone, aldosterone plus eplerenone or hydralazine. They were then implanted with an osmotic mini-pump that infused either aldosterone or the vehicle. Systolic blood pressure (SBP) was measured weekly by the tail-cuff method. After 8 weeks, plasma aldosterone concentration (PAC) and renin activity (PRA) were determined by radioimmunoassay. Aortic apoptosis was examined by TUNEL assay. The levels of cytochrome c and caspase-3 were determined by Western blotting and the expression of Bax and Bcl-2 was detected by immnuohistochemistry and Western blotting. The results showed that as compared with control group, aldosterone-infused rats exhibited: (1) an increase in SBP; (2) significantly elevated PAC with depressed PRA; (3) elevated aortic vascular cell apoptosis accompanied with higher levels of cytochrome c and activated caspase-3; and (4) significantly up-regulated Bax protein with down-regulated Bcl-2. These effects of aldosterone were significantly inhibited after co-administration with eplerenone but not with hydralazine. It was concluded that aldosterone induced vascular cell apoptosis by its direct effect on the aorta via mineralocorticoid receptors and independently of blood pressure, which may contribute to aldosterone-mediated vascular injury.
9.Association of Polymorphisms in Angiotensin Ⅱ Receptor Genes with Aldosterone-producing Adenoma
OUYANG JINZHI ; WU ZHUN ; XING JINCHUN ; YAN YONGJI ; ZHANG GUOXI ; WANG BAOJUN ; LI HONGZHAO ; MA XIN ; ZHANG XU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2011;31(3):301-305
This study examined the association of polymorphisms in angiotensin Ⅱ receptor genes (AT1R and AT2R) with the risk for aldosterone-producing adenoma (APA) in a Chinese Han population.Four polymorphisms including rs5182 (573T/C) in exon 4,rs5186 (1166A/C) in 3'-untranslated region (3'-UTR) in AT1R gene and rs5194 (2274G/A) in 3'-UTR,rs1403543 (1675G/A) in intron 1 in AT2R gene were detected in 148 APA patients and 192 normal subjects (serving as control) by using a MGB-Taqman probe.The distribution of genotypes of each locus was in accordance with Hardy-Weinberg Equilibrium (HWE) in the APA and control groups (P>0.05).The allele A frequency at rs5194 was significantly higher in the APA group (0.49) than in the control group (0.35) (X2=12.08,P=0.001).Subjects with homozygotic genotype AA and heterozygotic genotype GA were at an increased risk for APA as compared to those with GG genotype (OR=2.66,95% CI=1.45-4.87; OR=1.67,95% CI=1.02-2.74).Furthermore,rs5194 single-nucleotide polymorphism (SNP) at AT2R gene was significantly associated with APA in additive (OR=1.64,95% CI=1.21-2.20,P=0.001),dominant (OR=1.94,95% CI=1.23-3.06,P=0.003),and recessive model (OR=2.01,95% CI=1.17-3.45,P=0.01).It was concluded that rs5194 polymorphism at AT2R gene was associated with the risk for APA,which may constitute a genetic marker of APA.
10.Association of serum thyrotropin level with papillary thyroid microcarcinoma
Huixian YAN ; Weijun GU ; Guoqing YANG ; Jianming BA ; Xianling WANG ; Jin DU ; Jinzhi OUYANG ; Nan JIN ; Zhaohui LYU ; Jingtao DOU ; Yiming MU ; Juming LU
Chinese Journal of Endocrinology and Metabolism 2014;(8):669-672
Objective To study whether preoperative serum thyrotropin ( TSH) concentration can be used for risk prediction of papillary thyroid microcarcinoma ( PTMC ) . Methods The cohort of this retrospective study consisted of 1 707 patients who underwent surgery on thyroid nodules at Chinese PLA General Hospital from October 1999toFebruary2011. 37.32%(n=637)ofthesepatientssufferedfromdifferentiatedthyroidcancer(DTC),and 14. 18%(n=242) of patients with DTC suffered from PTMC. Results (1) The mean TSH level in patients with DTC was significantly higher than that in patients with benign thyroid nodules [(1. 99(1. 25-3. 19) vs 1. 48 (0. 85-2. 32) mU/L, P<0. 01]. DTC with diameter greater than 10 mm had higher serum TSH level compared with that in benign thyroid nodules[2. 04(1. 26-3. 36) vs 1. 45(0. 83-2. 30), P<0. 01]. Serum TSH level was not significantly raised in cases where-as the diameter of tumor was 10 mm or less. (2) With the increasing level of TSH, the prevalence of DTC and tumours with diameter greater than 10 mm rose significantly, but the increasing trend was not significant in PTMC. (3) Raised TSH level was an independent risk factor of DTC based on Binary logistic regression. Conclusions Serum TSH is an independent risk predictor of DTC, it is an independent risk predictor of the diameter of DTC greater than 10 mm, but it is not a good risk predictor in PTMC.