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Sun G.,Shenzhen Pingshan Peoples Hospital | Jia Y.,Guangxi Normal University | Meng J.,Third Peoples Hospital of Shenzhen | Ou M.,Guilin 181st Hospital | And 5 more authors.
Molecular Medicine Reports | Year: 2017

Thrombophilia is a multifactorial disorder involving environmental and genetic factors. Well-known factors that result in predisposition to congenital disorders associated with thrombophilia include antithrombin deficiency, protein C and S deficiency, Factor V Leiden mutation, abnormal prothrombin and antiphospholipid syndrome. The present study revealed an association between a mutation of the F2 gene, which codes for coagulation factor II, thrombin, and the risk of thrombophilia in a Han Chinese family, of which four members (I-2, II-2, II-3 and III-1) had a history of deep venous thromboembolism. The disease was measured in this family using laboratory measurements and computed tomography angiography. To identify the abnormality underlying the increased thrombophilia risk, whole-exome sequencing technology was used to analyze two affected individuals (II-2 and III-1). An exonic missense F2 mutation, T165M (NM-000506:c.C494T:p.T165M;rs5896), was identified from a total of 2,222 and 2,203 genetic variations observed in the two affected individuals, respectively, which were subsequently filtered and confirmed using Sanger sequencing. I-2, II-3 and III-1 shared this mutation with the proband (II-2), and II-6 had a heterozygous form of the mutation. This deleterious mutation was not identified in normal controls. The present study may improve understanding of the function of the F2 gene.


Chen W.,Jinan University | Tan K.,Ningbo No 2 Hospital | Huang J.,Jinan University | Yu X.,Jinan University | And 5 more authors.
Connective Tissue Research | Year: 2014

Objectives: Our aim in this study was to identify and examine the differential expression of microRNAs in patients with systemic lupus erythematosus (SLE). Methods: We employed high-quality, high-throughput Solexa sequencing to clone and identify microRNAs in SLE patients and a control group. Results: From the sequencing data, we identified numerous microRNAs displaying significantly different levels of expression in patients with SLE and in healthy controls. The 212 and 199 microRNAs were upregulated and downregulated, respectively. Only 61 novel microRNAs exhibited significantly different levels of expression in the two groups. The target genes of the novel microRNAs identified in the SLE group were found to have cell metabolism functions. We also analyzed the chromosomal locations of the microRNAs with high level of expression between the two groups. A profile comparison revealed that the majority of transcripts were expressed at a similar level. The functional classes of the most abundant microRNAs were equally represented on each chromosome. Conclusion: We identified novel and known microRNAs significantly enhancing our understanding of the microRNA expression profiles of SLE patients. These data also provide insight into the function of microRNAs in SLE and provide new strategies for future therapies. © 2014 Informa Healthcare USA, Inc.


Niu H.-T.,Sun Yat Sen University | Niu H.-T.,Chinese Academy of Sciences | Zhou Q.-M.,Sixth People Hospital of Shenzhen | Wang F.,Sun Yat Sen University | And 8 more authors.
Pigment Cell and Melanoma Research | Year: 2013

Summary: Acral and mucosal melanomas, the two most common subtypes of melanoma in China, exhibit different genetic alterations and biologic behavior compared with other subtypes of melanomas. The purpose of this study was to identify the genetic alterations in patients with acral or mucosal melanomas in southern China. Fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) analysis, polymerase chain reaction (PCR), and quantitative real-time reverse transcriptase PCR (qRT-PCR) were used to assess the anaplastic lymphoma kinase (ALK) break points. Furthermore, a mass spectrometry-based genotyping platform was used to analyze 30 acral melanomas and 28 mucosal melanomas to profile 238 known somatic mutations in 19 oncogenes. ALK break points were identified in four acral cases (6.9%). Eight (13.8%) cases harbored BRAF mutations, six (10.3%) had NRAS mutations, four (6.9%) had KIT mutations, two (3.5%) had EGFR mutations, two (3.5%) had KRAS mutations, two (3.5%) had MET mutations, one (1.7%) had an HRAS mutation, and one (1.7%) had a PIK3CA mutation. Two cases exhibited co-occurring mutations, and one case with a BRAF mutation had a translocation in ALK. This study represents a comprehensive and concurrent analysis of the major recurrent oncogenic mutations involved in melanoma cases from southern China. These data have implications for both clinical trial designs and therapeutic strategies. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Chen P.-F.,Third Peoples Hospital Of Shenzhen | He X.-F.,Changzhi Medical College | Huang G.-H.,Southern Medical University | Wang W.,The Second Peoples Hospital Of Zhuhai | Qiu Z.-H.,The Third Peoples Hospital Of Shenzhen
Technology in Cancer Research and Treatment | Year: 2016

The previously published data on the association between the cytochrome P450 1B1 Leu432Val, Asn453Ser, and Ala119Ser polymorphisms and lung cancer risk have remained controversial. Hence, we performed a meta-analysis to investigate the association between cytochrome P450 1B1 Leu432Val, Asn453Ser, and Ala119Ser polymorphisms and lung cancer risk under different inheritance models. A total of 22 studies were identified, including 2881 cases and 3653 controls for Leu432Val polymorphism (from 13 studies), 3009 cases and 3887 controls for Asn453Ser polymorphism (from 5 studies), and 1301 cases and 2045 controls for Ala119Ser polymorphism (from 4 studies). Overall, significant association was observed between cytochrome P450 1B1 Leu432Val polymorphism and lung cancer risk (dominant model: odds ratio = 1.29, 95% confidence interval = 1.08-1.53; recessive model: odds ratio = 1.21, 95% confidence interval = 1.05-1.39; additive model: odds ratio = 1.43, 95% confidence interval = 1.21-1.69) when all the eligible studies were pooled into the meta-analysis. In the further stratified and sensitivity analyses, significantly increased lung cancer risk was also observed in caucasians and smokers. No significant association was observed between cytochrome P450 1B1Asn453Ser and Ala119Ser polymorphisms and lung cancer risk in overall analysis. In summary, this meta-analysis suggests that cytochrome P450 1B1Leu432Val polymorphism is associated with increased lung cancer risk in caucasians and smokers. © 2015, © The Author(s) 2015.


Wu W.,Jinan University | He Y.,Third Peoples Hospital of Shenzhen | Lu J.,Third Peoples Hospital of Shenzhen | Lu Y.,Jinan University | And 2 more authors.
PLoS ONE | Year: 2015

Background The prevalence of carbapenem-resistant Acinetobacter baumannii in hospitals has been increasing worldwide. This study aims to investigate the carbapenemase genes and the clonal relatedness among A. baumannii clinical isolates in a Chinese hospital. Methods Carbapenemase genes and the upstream locations of insertion sequences were detected by polymerase chain reaction (PCR), and the clonal relatedness of isolates was determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Results A total of 231 nonduplicate carbapenemase gene-harboring A. baumannii clinical isolates recovered from Shenzhen People's Hospital, were investigated between 2002 and 2009. blaOXA-23-like, blaOXA-58-like, blaOXA-40-like, and ISAba1-blaOXA-51-like were identified in 119, 107, 1, and 4 isolates, respectively. IS1008-δISAba3, ISAba3, and ISAba1 were detected upstream of the blaOXA-58-like gene in 69, 35, and 3 isolates, respectively. All blaOXA-23-like genes but one had an upstream insertion of ISAba1. blaOXA-58-like was the most common carbapenemase gene in A.baumannii before 2008, thereafter blaOXA-23-like became rapidly prevalent and replaced blaOXA-58-like in 2009. The majority of blaOXA-58-like-carrying isolates showed lower level of resistance to imipenem and meropenem (minimum inhibitory concentrations (MICs), 1 μg/ml to 16 μg/ml), compared with the majority of blaOXA-23-like-carrying isolates (MICs, 16 μg/ml to 64 μg/ml for both imipenem and meropenem). All 231 blaOXA carbapenemase gene-harboring isolates belonged to 14 PFGE types (A-N), and three dominant clones A, J, and H accounted for 43.3%, 42.0%, and 8.2% of the tested isolates, respectively. Clone A (sequence type ST92/ST208) with blaOXA-58-like was the most prevalent before 2008. Clone H (ST229) with blaOXA-23-like became striking between 2007 and 2008. Clone J (ST381) with blaOXA-23-like rapidly spread and replaced clones A and H in 2009. Conclusion This study is the first to reveal that the distinct blaOXA-23-like-carrying A. baumannii ST381 displaced the previously prevalent blaOXA-58-like-carrying A. baumannii ST92/ST208, resulting in the rapidly increasing resistance to carbapenems in A. baumannii in Shenzhen People's Hospital in 2009. © 2015 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Zeng W.,Third Peoples Hospital of Shenzhen
Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology | Year: 2013

This study aimed at evaluating the efficacy and safety of a combination treatment of entecavir and Peginterferon alpha-2a for HBeAg positive chronic hepatitis B patients with high serum hepatitis B viral loads. 60 treatment-naive HBeAg-positive CHB patients with high serum hepatitis B viral loads were enrolled and randomly divided into three groups: group A received Peginterferon alpha-2a monotherapy for 48 weeks (n = 20); group B received entecavir monotherapy for more than 48 weeks (n = 20); group C received Peginterferona alpha-2a combined with entecavir for 12 weeks, then Peginterferon alpha-2a monotherapy for 36 weeks (n = 20). Virological response, ALT normalization, HBeAg and HBsAg seroclearance rate were analysed at the end of 4, 12 and 24 weeks after the treatment. The ratio of undetectable hepatitis B virus (HBV) DNA were 50% and 10%, 95% and 25% and 100% and 30% in group C and group A respectively, 50% and 20%, 95% and 75% and 100% and 90% in group C and group B respectively at the end of 4, 12 and 24 weeks of treatment. The differences were significant between group C and A (Z = -4.6, P < 0.001), group C and B (Z = -2.53, P = 0.0114). ALT normalization rate was significantly lower in group A than that of group C (Z = -2.63, P = 0.0086). HBeAg levels declined more in group C than the other two groups after 24 weeks of treatment. For HBeAg positive chronic hepatitis B patients with high serum hepatitis B viral loads, combination treament of Peginterferon alpha-2a with entecavir is more effective than Peginterferon alpha-2a monotherapy in virologic response and ALT normalization after 24 weeks of treatment.


Tian Y.,Nanjing Medical University | Wang K.,Nanjing Medical University | Wang Z.,Nanjing Medical University | Li N.,Third Peoples Hospital of Shenzhen | Ji G.,Nanjing Medical University
Carcinogenesis | Year: 2013

Chronic colonic inflammation is a known risk factor for colorectalcancer (CRC). Glutamine (GLN) supplementation has shownits anti-inflammation benefit in experimental colitis. WhetherGLN is effective in preventing colon carcinogenesis remains tobe investigated. The chemopreventive activity of GLN was evaluatedin the mouse model of dextran sulfate sodium (DSS)/azoxymethane(AOM)-induced colitis-associated CRC in this study. Mice were treated with DSS/AOM and randomized to receiveeither a control diet or GLN-enriched diet intermittently of thestudy. The disease activity index was evaluated weekly. On day80 of the experiment, the entire colon and rectum were processedfor histopathologic examination and further evaluation. Pro-inflammatory mediators and cytokines were measured byenzyme-linked immunosorbent assay, real-time-PCR and westernblot analysis. Here, we show that after GLN-enriched diet, the colitis presented a statistical improvement and tumors burdendecreased significantly. This was accompanied by lower activityof nuclear factor-κB (NF-κB), decreased expression of cyclooxygenase-2 and inducible nitric oxide synthase, lower expression ofcytokines and chemokines as well as reduced proliferation andinduced apoptosis in the colons of colitis-associated CRC mice. Our data demonstrate the protective/preventive effect of GLN inthe progression of colitis-associated CRC, which was correlatedwith a dampening of inflammation and NF-κB activity and with adecrease of inflammatory protein overexpression. © The Author 2013. Published by Oxford University Press. All rights reserved.


Huang J.,Guangdong Medical College | Song G.,Third Peoples Hospital of Shenzhen | Yin Z.,Guangdong Medical College | Luo X.,Guangdong Medical College | Ye Z.,Guangdong Medical College
Modern Rheumatology | Year: 2014

Objectives. Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by new bone formation. Recent evidence suggests that new bone formation in AS may be due to upregulation of Wnt signaling in the osteoblastic pathway secondary to low serum Dickkopf homolog 1 (Dkk-1) levels. And miR-29a orchestrates osteoblast differentiation through direct targeting and negative regulation of Dkk-1. Methods. We initially validated the expression levels of miR-29a in the peripheral blood mononuclear cells (PBMCs) of AS patients (n = 30), rheumatoid arthritis (RA) patients (n = 30) and healthy controls (n = 30) using real-time quantitative reverse transcription PCR (qRT-PCR). Correlation analysis was assessed between miR-29a level in PBMCs of AS patients and disease activity indexes, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis function index (BASFI) and modified Stoke ankylosing spondylitis spinal score (mSASSS). Results. Significantly higher expression of miR-29a was observed in PBMCs of AS patients (Ct 9.18 ± 1.96) compared with that in RA patients (10.97 ± 0.70, p < 0.001) and healthy controls (Ct 11.45 ± 1.23, p < 0.001). There was no significant difference between RA patients and healthy controls in miR-29a expression (p > 0.05). Elevated miR-29a expression is not correlated with disease activity index (p > 0.05). A weak correlation was found between elevated miR-29a expression and mSASSS (r = -0.393, p = 0.032). Conclusions. We report for the first time elevated miR-29a expression in PBMCs of patients with ankylosing spondylitis, and miR-29a might be used as a useful diagnostic marker in new bone formation but cannot reflect disease activity. © 2014 Japan College of Rheumatology.


PubMed | Jinan University and Third Peoples Hospital of Shenzhen
Type: Journal Article | Journal: PloS one | Year: 2015

The prevalence of carbapenem-resistant Acinetobacter baumannii in hospitals has been increasing worldwide. This study aims to investigate the carbapenemase genes and the clonal relatedness among A. baumannii clinical isolates in a Chinese hospital.Carbapenemase genes and the upstream locations of insertion sequences were detected by polymerase chain reaction (PCR), and the clonal relatedness of isolates was determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing.A total of 231 nonduplicate carbapenemase gene-harboring A. baumannii clinical isolates recovered from Shenzhen Peoples Hospital, were investigated between 2002 and 2009. blaOXA-23-like, blaOXA-58-like, blaOXA-40-like, and ISAba1-blaOXA-51-like were identified in 119, 107, 1, and 4 isolates, respectively. IS1008-ISAba3, ISAba3, and ISAba1 were detected upstream of the blaOXA-58-like gene in 69, 35, and 3 isolates, respectively. All blaOXA-23-like genes but one had an upstream insertion of ISAba1. blaOXA-58-like was the most common carbapenemase gene in A.baumannii before 2008, thereafter blaOXA-23-like became rapidly prevalent and replaced blaOXA-58-like in 2009. The majority of blaOXA-58-like-carrying isolates showed lower level of resistance to imipenem and meropenem (minimum inhibitory concentrations (MICs), 1 g/ml to 16 g/ml), compared with the majority of blaOXA-23-like-carrying isolates (MICs, 16 g/ml to 64 g/ml for both imipenem and meropenem). All 231 blaOXA carbapenemase gene-harboring isolates belonged to 14 PFGE types (A-N), and three dominant clones A, J, and H accounted for 43.3%, 42.0%, and 8.2% of the tested isolates, respectively. Clone A (sequence type ST92/ST208) with blaOXA-58-like was the most prevalent before 2008. Clone H (ST229) with blaOXA-23-like became striking between 2007 and 2008. Clone J (ST381) with blaOXA-23-like rapidly spread and replaced clones A and H in 2009.This study is the first to reveal that the distinct blaOXA-23-like-carrying A. baumannii ST381 displaced the previously prevalent blaOXA-58-like-carrying A. baumannii ST92/ST208, resulting in the rapidly increasing resistance to carbapenems in A. baumannii in Shenzhen Peoples Hospital in 2009.


PubMed | Third Peoples Hospital of Shenzhen
Type: Journal Article | Journal: Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology | Year: 2013

This study aimed at evaluating the efficacy and safety of a combination treatment of entecavir and Peginterferon alpha-2a for HBeAg positive chronic hepatitis B patients with high serum hepatitis B viral loads.60 treatment-naive HBeAg-positive CHB patients with high serum hepatitis B viral loads were enrolled and randomly divided into three groups: group A received Peginterferon alpha-2a monotherapy for 48 weeks (n = 20); group B received entecavir monotherapy for more than 48 weeks (n = 20); group C received Peginterferona alpha-2a combined with entecavir for 12 weeks, then Peginterferon alpha-2a monotherapy for 36 weeks (n = 20). Virological response, ALT normalization, HBeAg and HBsAg seroclearance rate were analysed at the end of 4, 12 and 24 weeks after the treatment.The ratio of undetectable hepatitis B virus (HBV) DNA were 50% and 10%, 95% and 25% and 100% and 30% in group C and group A respectively, 50% and 20%, 95% and 75% and 100% and 90% in group C and group B respectively at the end of 4, 12 and 24 weeks of treatment. The differences were significant between group C and A (Z = -4.6, P < 0.001), group C and B (Z = -2.53, P = 0.0114). ALT normalization rate was significantly lower in group A than that of group C (Z = -2.63, P = 0.0086). HBeAg levels declined more in group C than the other two groups after 24 weeks of treatment.For HBeAg positive chronic hepatitis B patients with high serum hepatitis B viral loads, combination treament of Peginterferon alpha-2a with entecavir is more effective than Peginterferon alpha-2a monotherapy in virologic response and ALT normalization after 24 weeks of treatment.

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