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Han Chen Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

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Ming Ni Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

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Yun Xu Department of Obstetrics and Gynaecology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

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Li-Yong Zhong Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

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Children with intracranial germ cell tumors may present premature sexual development via either gonadotrophin-releasing hormone (GnRH)-dependent cause or GnRH-independent cause. We conducted a single-center retrospective study on 37 precocious puberty (PP) patients with intracranial germ cell tumors and 25 age-matched prepubertal patients with elevated human chorionic gonadotropin (hCG) levels. Classification of PP was derived from hCG, gonadotropin and sex steroid levels and their changes. Five boys were assigned to GnRH-dependent group (G1). Thirty-one boys and one girl were assigned to GnRH-independent group (G2) with a median hCG of 76.75 (8.29–2747) IU/L. Seven boys and 18 girls were conducted as controls, with a median hCG of 17.12 (2.91–1062) IU/L. Patients in G1 had constant pubertal LH and testosterone levels after tumor complete response. Patients in G2 had hCG levels that decreased simultaneously with testosterone/estradiol levels, prior to tumor regression. The differences in hCG levels and the gender ratio were significant between G2 and controls (P = 0.006 and P < 0.001, separately). Among intracranial germ cell tumor patients with positive hCG, boys with significantly higher hCG levels more easily developed PP. Our results suggest that GnRH-independent PP commonly regresses together with tumor regression. In comparison, results were inconclusive in tying tumor regression to the regression of GnRH-dependent PP.

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Hong-Jun Song Department of Nuclear Medicine, Postgraduate Department, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233, China

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Yan-Li Xue Department of Nuclear Medicine, Postgraduate Department, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233, China
Department of Nuclear Medicine, Postgraduate Department, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233, China

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Yan-Hong Xu Department of Nuclear Medicine, Postgraduate Department, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233, China
Department of Nuclear Medicine, Postgraduate Department, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233, China

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Zhong-Ling Qiu Department of Nuclear Medicine, Postgraduate Department, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233, China

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Quan-Yong Luo Department of Nuclear Medicine, Postgraduate Department, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233, China

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Differentiated thyroid cancer (DTC) is usually indolent with good prognosis and long-term survival. However, DTC distant metastasis is often a grave event and accounts for most of its disease-specific mortality. The major sites of distant metastases are the lung and bone. Metastases to the brain, breast, liver, kidney, muscle, and skin are rare or relatively rare. Nevertheless, recognizing rare metastases from DTC has a significant impact on the clinical decision making and prognosis of patients. 131I single photon emission computed tomography/computed tomography (131I-SPECT/CT) can provide both metabolic and anatomic information about a lesion; therefore, it can better localize and define the 131I-WBS findings in DTC patients. In this pictorial review, the imaging features of a range of rare metastases from DTC are demonstrated, with a particular emphasis on the 131I-SPECT/CT diagnostic aspect.

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Luming Wu Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Jing Xie Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Yan Qi Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Tingwei Su Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Lei Jiang Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Weiwei Zhou Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Yiran Jiang Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Cui Zhang Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Xu Zhong Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Yanan Cao Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Weiqing Wang Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China

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Adrenal incidentalomas are the most frequent human neoplasms. Recent genomic investigations on functional adrenocortical tumors have demonstrated that somatic mutations in PRKACA and KCNJ5 responsible for the development of adrenocortical adenomas (ACAs) are associated with hypercortisolism and aldosteronism, respectively. Several studies have identified CTNNB1 mutations in ACAs and have been mostly involved in the tumorigenesis of non-functional ACA (NFACA). However, integrated genomic characterization of NFACAs is lacking. In the current study, we utilized pan-genomic methods to comprehensively analyze 60 NFACA samples. A total of 1264 somatic mutations in coding regions among the 60 samples were identified, with a median of 15 non-silent mutations per tumor. Twenty-two NFACAs (36.67%) had genetic alterations in CTNNB1. We also identified several somatic mutations in genes of the cAMP/PKA pathway and KCNJ5. Histone modification genes (KMT2A, KMT2C, and KMT2D) were altered in 10% of cases. Germline mutations of MEN1 and RET were also found. Finally, by comparison of our transcriptome data with those available in the TCGA, we illustrated the molecular characterization of NFACA. We revealed the genetic profiling and molecular landscape of NFACA. Wnt/β-catenin pathway activation as shown ssby nuclear and/or cytoplasmic β-catenin accumulation is frequent, occurring in about one–third of ACA cases. cytochrome P450 enzymes could be markers to reveal the functional status of adrenocortical tumors. These observations strongly suggest the involvement of the Wnt/β-catenin pathway in benign adrenal tumorigenesis and possibly in the regulation of steroid secretion.

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Luming Wu Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Jing Xie Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Yan Qi Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Tingwei Su Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Lei Jiang Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Weiwei Zhou Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Yiran Jiang Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Cui Zhang Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Xu Zhong Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Yanan Cao Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Weiqing Wang Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China

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Feng Wu Department of Endocrinology, The Third Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
Department of Pathology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Fuxingzi Li Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Xiao Lin Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Feng Xu Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Rong-Rong Cui Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Jia-Yu Zhong Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Ting Zhu Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Su-Kang Shan Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Xiao-Bo Liao Department of Cardiovascular Surgery, the Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Ling-Qing Yuan Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Zhao-Hui Mo Department of Endocrinology, The Third Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Tumour-derived exosomes under hypoxic conditions contain informative miRNAs involved in the interaction of cancer and para-carcinoma cells, thus contributing to tissue remodelling of the tumour microenvironment (TME). Exosomes isolated from hypoxic papillary thyroid cancer cells, BCPAP cells and KTC-1 cells enhanced the angiogenesis of human umbilical vein endothelial cells (HUVECs) compared with exosomes isolated from normal thyroid follicular cell line (Nthy-ori-3-1), normoxic BCPAP or KTC-1 cells both in vitro and in vivo. miR-21-5p was significantly upregulated in exosomes from papillary thyroid cancer BCPAP cells under hypoxic conditions, while the exosomes isolated from hypoxic BCPAP cells with knockdown of miR-21-5p attenuated the promoting effect of angiogenesis. In addition, our experiment revealed that miR-21-5p directly targeted and suppressed TGFBI and COL4A1, thereby increasing endothelial tube formation. Furthermore, elevated levels of exosomal miR-21-5p are found in the sera of papillary thyroid cancer patients, which promote the angiogenesis of HUVECs. Taken together, our study reveals the cell interaction between hypoxic papillary thyroid cancer cells and endothelial cells, elucidating a new mechanism by which hypoxic papillary thyroid cancer cells increase angiogenesis via exosomal miR-21-5p/TGFBI and miR-21-5p/COL4A1 regulatory pathway.

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Feng Wu Department of Endocrinology, The Third Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
Department of Pathology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Fuxingzi Li Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Xiao Lin Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Feng Xu Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Rong-Rong Cui Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Jia-Yu Zhong Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Ting Zhu Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Su-Kang Shan Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Xiao-Bo Liao Department of Cardiovascular Surgery, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Ling-Qing Yuan Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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Zhao-Hui Mo Department of Endocrinology, The Third Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

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