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Wu P.,Peking University | Wu P.,National Urological Cancer Center | Zhang N.,Capital University of Medicine Science | Wang X.,Peking University | And 8 more authors.
Journal of Human Genetics | Year: 2012

Von Hippel-Lindau (VHL) disease is an autosomal dominant familial cancer syndrome caused by germline mutations in VHL tumor suppressor gene. It is characterized by hemangioblastoma in central nervous system and retina, renal cell carcinoma or cyst, pheochromocytoma, pancreatic cyst and tumor, endolymphatic-sac tumor, and papillary cystadenoma in epididymis and broad ligament. Here, we used PCR-direct sequencing and universal primer quantitative fluorescent multiplex PCR (UPQFM-PCR) to detect VHL mutations in 16 patients clinically diagnosed with VHL disease. PCR-direct sequencing detected 12 germline mutations (75%, 12/16), in which a novel mutation of c.451A>T/p.Ile151Phe found in one proband had not been reported previously. UPQFM-PCR found two large deletions (12.5%, 2/16). The two remaining patients carried non-typical disease-causing mutations, including one silent mutation (c.481C>A/p.Arg161Arg) and one mutation in 3′-UTR (c.642+70C>A). Remarkably, 56.3% (9/16) probands did not have family history of VHL disease, suggesting the higher frequency of de novo mutations in Chinese patients. We also summarized Chinese VHL disease patients with VHL mutation findings published in the literature to provide information about the spectrum of VHL mutations in Chinese VHL disease patients. © 2012 The Japan Society of Human Genetics All rights reserved.


Zhang N.,Capital University of Medicine science | Gong K.,Peking University | Zhang X.,Capital University of Medicine science | Yang Y.,Capital University of Medicine science | Na Y.,Peking University
Urologic Oncology: Seminars and Original Investigations | Year: 2010

Objectives: We evaluate the clinical manifestations, management, and prognostic characteristics of scrotal extramammary Paget's disease (EMPD). Methods: The study comprised 25 patients with scrotal EMPD at our institute from January 1982 to February 2005, with all available clinical and pathological data reviewed. Results: Of these 25 patients, 1 received radiotherapy and 24 received local wide excisions. In 24 operated patients, 7 had local recurrence and/or metastasis of groin lymph node. Five of the 7 with recurrence had a positive surgical margin postoperatively and they received a second local extensive excision. One of the 7 with recurrence and metastasis of the groin lymph node had a second local extensive excision with groin lymphadenectomy, and the last one who only had metastasis of the groin lymph node had a groin lymphadenectomy. Four of 13 patients with dermal invasion by Paget's cell had metastasis. None of the other 12 patients without dermal invasion had metastasis. However, there was no statistical metastasis rate difference (P = 0.096) between the patients with dermal invasion by Paget's cell and without. There was no statistical difference (P = 0.947) in mean delay time from onset of symptoms to diagnosis between the 2 groups either. The follow-up duration varies from 17 to 243 months (mean 119 + 86.2 months). One patient with stage D died of EMPD of the scrotum. Conclusions: We found that EMPD of the scrotum is usually a slow progressive disease, mainly seen in elderly patients, and has a good prognosis when there is noninvasive disease. The primary treatment for EMPD of the scrotum is wide surgical excision. The key to decreasing tumor recurrence, however, is a precise, preoperative histological examination to define the range of the lesion. © 2010 Elsevier Inc. All rights reserved.


Ning X.-H.,Peking University | Ning X.-H.,Capital University of Medicine Science | Zhang N.,Capital University of Medicine Science | Li T.,Peking University | And 14 more authors.
Cancer Research | Year: 2014

Von Hippel-Lindau (VHL) disease is a rare autosomal dominant cancer syndrome. A phenomenon known as genetic anticipation has been documented in some hereditary cancer syndromes, where it was proved to relate to telomere shortening. Because studies of this phenomenon in VHL disease have been relatively scarce, we investigated anticipation in 18 Chinese VHL disease families. We recruited 34 parent-child patient pairs (57 patients) from 18 families with VHL disease. Onset age was defined as the age when any symptom or sign of VHL disease first appeared. Anticipation of onset age was analyzed by paired t test and the other two special tests (HV and RY2). Relative telomere length of peripheral leukocytes was measured in 29 patients and 325 healthy controls. Onset age was younger in child than in parent in 31 of the 34 parent-child pairs. Patients in the first generation had older onset age with longer age-adjusted relative telomere length, and those in the next generation had younger onset age with shorter age-adjusted relative telomere length (P < 0.001) in the 10 parent-child pairs from eight families with VHL disease. In addition, relative telomere length was shorter in the 29 patients with VHL disease than in the normal controls (P = 0.003). The anticipation may relate to the shortening of telomere length in patients with VHL in successive generations. These findings indicate that anticipation is present in families with VHL disease and may be helpful for genetic counseling for families with VHL disease families and for further understanding the pathogenesis of VHL disease. ©2014 AACR.


Wu P.,Peking University | Zhang N.,Capital University of Medicine Science | Wang X.,Peking University | Zhang C.,Peking University | And 3 more authors.
PLoS ONE | Year: 2012

Co-expression of erythropoietin (Epo) and erythropoietin receptor (EpoR) has been found in various non-hematopoietic cancers including hereditary and sporadic renal cell carcinomas (RCC), but the Epo/EpoR autocrine and paracrine mechanisms in tumor progression have not yet been identified. In this study, we used RNA interference method to down-regulate EpoR to investigate the function of Epo/EpoR pathway in human RCC cells. Epo and EpoR co-expressed in primary renal cancer cells and 6 human RCC cell lines. EpoR signaling was constitutionally phosphorylated in primary renal cancer cells, 786-0 and Caki-1 cells, and recombinant human Epo (rhEpo) stimulation had no significant effects on further phosphorylation of EpoR pathway, proliferation, and invasiveness of the cells. Down-regulation of EpoR expression in 786-0 cells by lentivirus-introduced siRNA resulted in inhibition of growth and invasiveness in vitro and in vivo, and promotion of cell apoptosis. In addition, rhEpo stimulation slightly antagonized the anti-tumor effect of Sunitinib on 786-0 cells. Sunitinib could induce more apoptotic cells in 786-0 cells with knockdown EpoR expression. Our results suggested that Epo/EpoR pathway was involved in cell growth, invasion, survival, and sensitivity to the multi-kinases inhibitor Sunitinib in RCC cells. © 2012 Wu et al.


Hua L.,Capital University of Medicine Science | Yang Z.,Capital University of Medicine Science | Liu H.,Capital University of Medicine Science
2012 5th International Conference on Biomedical Engineering and Informatics, BMEI 2012 | Year: 2012

Non-synonymous SNPs (nsSNPs), also known as Single Amino acid Polymorphisms (SAPs), are likely to affect the function of the proteins accounting for susceptibility to complex disease for their altering the encoded amino acid sequence. Recent advances in genetic studies found that the non-synonymous variations locating in disordered regions are functionally important. We therefore considered predicting deleterious SAPs based on both protein interaction network and disordered protein property. We used one of functional prediction algorithms of nsSNPs, PolyPhen-2, to distinguish SAPs as damaging or benign. Four classifiers: naïve Bayes, k-Nearest Neighbor (kNN), Support Vector Machine (SVM) and Random Forests (RF) were used to classify SAPs. As a result, the prediction accuracies of four classifiers are all over 70%, and the three features (degree, clustering coefficient and disorder score) were found to be potential predictor variables to classify nsSNPs. © 2012 IEEE.


Jun L.,Capital University of Medicine science | ChangYi S.,Capital University of Medicine science
Indian Journal of Surgery | Year: 2015

Early intestinal obstruction is easily misdiagnosed. Many physicians consider terminal bouton if computed tomography (CT) scan is done. However, different examinations provide diverse information and significance. This retrospective, randomized, clinical study investigated the diagnostic value of three imaging modalities for intestinal obstruction, supine and upright (or decubitus) plain abdominal radiography, contrast radiography using Gastrografin, and 64 multi-slice spiral CT (MSCT). A total 142 patients with intestinal obstruction were examined. The diagnostic accuracy of plain radiography, contrast radiography, and MSCT for detecting small bowel obstruction was 62.5, 85, and 77.5 %, for localizing the obstruction was 0, 90, and 78.75 %, and for determining the cause of obstruction was 0, 71, and 65 %, respectively. The diagnostic accuracy for detecting large bowel obstruction was 53.23, 73.17, and 92 %, and for localizing the obstruction was 38.17, 60.98, and 98 %, respectively. The diagnostic accuracy of MSCT in determining the cause of obstruction was 91 %. None of the patients administered Gastrografin experienced any adverse effects. In conclusion, MSCT has great diagnostic value in identifying the site and cause of intestinal obstruction, especially in cases of large bowel obstruction. Contrast radiography using Gastrografin was effective in diagnosing and treating small bowel obstruction, making it a beneficial adjunct to MSCT. © 2015, Association of Surgeons of India.


Hua L.,Capital University of Medicine Science | Zheng W.,Capital University of Medicine Science | Liu H.,Capital University of Medicine Science | Yan Y.,Capital University of Medicine Science
Proceedings - 2010 3rd International Conference on Biomedical Engineering and Informatics, BMEI 2010 | Year: 2010

There is a growing consideration that gene-gene interactions may play important roles in complex diseases etiology. The simultaneous genotyping of hundreds of thousands of single nucleotide polymorphisms (SNP) have provided an excellent chance to study genetic epidemiology from molecular network. In this paper, we performed genome-wide gene-gene interaction associated with rheumatoid arthritis (RA) using RA datasets provided by the Genetic Analysis Workshop 15 (GAW 15) Problem 2. The results reported here that there were 14 significant SNP-SNP pairs associated with RA and the interaction between rs744877 and rs238510 was the strongest SNP-SNP pair contributing to disease with the maximal interaction score defined in our paper. ©2010 IEEE.


Hua L.,Capital University of Medicine Science | Yang Z.,Capital University of Medicine Science | Liu H.,Capital University of Medicine Science
Proceedings - 2011 4th International Conference on Biomedical Engineering and Informatics, BMEI 2011 | Year: 2011

There is a growing consideration that gene-gene interactions may play important roles in complex diseases etiology. The simultaneous genotyping of hundreds of thousands of single nucleotide polymorphisms (SNP) have made genetic epidemiology studies come into a new phase. Using molecular network to research complex diseases and find related information is a novel and powerful method. Here, we applied GLOSSI (Gene-loci Set Analysis) to test the association of a group of SNPs (loci-set) with complex disease phenotypes. At the same time, all SNPs were used to construct well designed genetic networks by Polymorphism Interaction Analysis (PIA) algorithm and by which we extracted gene-gene sub-networks associated with complex diseases. The results were compared to explore the most significant SNP groups which might contribute to interpret disease etiology. We apply Rheumatoid Arhtritis (RA) datasets provided by the Genetic Analysis Workshop 15 (GAW 15) Problem 2 and positional gene sets for each human chromosome and each cytogenetic band were derived from the publicly accessible Molecular Signature Database (MSigDB). The results reported here that there were no significant SNP loci sets of MSigDB associated with RA but three SNP groups extracted from genetic networks, offering molecular support for the current grouping of the genes. Furthermore, we found that the hub genes of gene-gene sub-networks were also most significant SNPs, such as CD160 (rs744877) and ALS2 (rs970595), were special relevant to RA, as supported by many previous reports. Our study is a new attempt to mine gene groups with genetic associations to complex diseases, which can be applied to large numbers of genetic markers. © 2011 IEEE.


Hua L.,Capital University of Medicine Science | Liu Y.,Capital University of Medicine Science | Gao L.,Capital University of Medicine Science | Li D.,Capital University of Medicine Science
Proceedings - 2011 4th International Conference on Biomedical Engineering and Informatics, BMEI 2011 | Year: 2011

The interaction between proteins is one of the most important features of protein functions. Behind protein-protein interactions there are relationship among protein domains physically to perform the necessary functions. Accordingly, we focus on our research on the domain features of co-regulation proteins sets, co-interaction proteins sets and co-regulation & co-regulation proteins sets. We applied aggregation factors to evaluate the domain features about above three protein sets. By random experiment, we approved that the aggregation factors were significant (p<0.01) in these three protein sets. That is to say, the same domains present more frequency in them than in other protein subsets. Furthermore, our results also showed that the same domains present more frequency in co-regulation & co-interaction subsets than in co-regulation subsets, which indicated that co-regulation protein sets & co-interaction protein sets are more likely protein sets which have the same domains. © 2011 IEEE.


PubMed | Capital University of Medicine Science
Type: Journal Article | Journal: Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale | Year: 2010

congenital anosmia is extremely rare and tends to present late. We report on a series of patients with congenital anosmia to analyze its clinical characteristics and present illustrative cases.retrospective chart review.tertiary care centre.thirty-five patients with congenital anosmia were reviewed. A thorough medical history taking, physical examination, and nasal endoscopy were performed in all patients. T&T olfactory testing (n = 33), olfactory event-related potentials (OERPs) (n = 33), and sinonasal computed tomography (CT) (n = 35) were carried out. Magnetic resonance images (MRIs) of the olfactory pathway (n = 34) were available. Serum sex hormones were tested (n = 33).physical examination, olfactory testing, MRI of the olfactory pathway, and serum sex hormones.twenty cases were isolated congenital anosmia (ICA). Fifteen cases were congenital anosmia with other anomalies, including 12 cases with Kallmann syndrome (KS), two with CHARGE syndrome, and one with hypoplasia of the nasal cavity and nasal sinus. T&T olfactory testing indicated anosmia (n = 33). No OERP was obtained (n = 33). CT scans indicated three abnormal patients, including two with unilateral choanal atresia and one with hypoplasia of the nasal cavity and sinus. MRI demonstrated aplasia or hypoplasia of the olfactory bulbs, tracts, and olfactory sulci (n = 34). Serum sex hormones were low in 12 patients with KS.early diagnosis of congenital anosmia on the basis of olfactory symptoms is difficult. MRI of the olfactory pathway plays an important role in anatomic location. ICA is the most common congenital anosmia. KS is the primary presentation of congenital anosmia with other anomalies.

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