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Zhang A.-Y.,University of Hong Kong | Zhang A.-Y.,Fourth Peoples Hospital Of Shenzhen | Lai C.-L.,University of Hong Kong | Huang F.-Y.,University of Hong Kong | And 4 more authors.
Journal of Gastroenterology | Year: 2017

Background: The association between the evolution of hepatitis B virus (HBV) quasispecies and the development of hepatocellular carcinoma (HCC) is unknown. Methods: We used deep sequencing to examine the dynamics of HBV quasispecies and their relationship to HCC development. Thirty-two chronic hepatitis B (CHB) patients with HCC (HCC group) and 32 matched CHB patients without HCC (controls) were recruited. Fourteen patients from each group had serial sera available up to 9 years before the time of the present study. Deep sequencing of the HBV pre-S regions was performed. HBV quasispecies complexity, diversity, and intrapatient prevalence of pre-S deletions/mutations were analyzed. Results: Compared with control patients, HCC patients had a significant greater quasispecies complexity (p = 0.04 at the nucleotide level), greater diversity (p = 0.004 and 0.009 at the nucleotide level and the amino acid level respectively), and a trend of greater complexity at the amino acid level (p = 0.065). HCC patients had a higher intrapatient prevalence of pre-S deletions and point mutations (at codons 4, 27, and 167) compared with the control patients (all p < 0.05). Longitudinal observation in the sera of 14 HCC patients showed that quasispecies complexity (p = 0.027 and 0.024 at the nucleotide level and the amino acid level respectively) and diversity (p = 0.035 and 0.031 at the nucleotide level and the amino acid level respectively) increased as the disease progressed to HCC. Conclusions: Increased HBV quasispecies complexity and diversity in the pre-S region, probably reflecting enhanced virus–host interplay, was associated with disease progression from CHB to HCC. © 2017 Japanese Society of Gastroenterology


Wei W.-B.,Fourth Peoples Hospital of Shenzhen | Hu X.,Sun Yat Sen University | Zhuang X.-D.,Sun Yat Sen University | Liao L.-Z.,Guangdong Pharmaceutical University | Li W.-D.,Guangdong Pharmaceutical University
Molecular and Cellular Biochemistry | Year: 2014

Diabetic cardiomyopathy (DCM) has become a major cause of diabetes-related morbidity and mortality. Increasing evidences have proved that hydrogen sulfide (H2S) fulfills a positive role in regulating diabetic myocardial injury. The present study was designed to determine whether GYY4137, a novel H2S-releasing molecule, protected H9c2 cells against high glucose (HG)-induced cytotoxicity by activation of the AMPK/mTOR signal pathway. H9c2 cells were incubated in normal glucose (5.5 mM), 22, 33, and 44 mM glucose for 24 h to mimic the hyperglycemia in DCM in vitro. Then we added 50, 100, and 200 μM GYY4137, and measured the cell viability, lactate dehydrogenase (LDH) enzyme activity, and mitochondrial membrane potential (MMP). 0.5 mM 5-amino-4-imidazole-carboxamide riboside (AICAR, an AMPK activator) and 1 mM adenine 9-β-d-arabinofuranoside (Ara-A, an AMPK inhibitor) were used to identity whether the AMPK/mTOR signal pathway was involved in GYY4137-mediated cardioprotection. We demonstrated that HG decreased cell viability and increased LDH enzyme activity in a concentration-dependent manner. 33 mM HG treatment for 24 h was chosen as our model group for further study. Both 100 and 200 μM GYY4137 treatments significantly attenuated HG-induced cell viability decrement, LDH enzyme activity increase, and MMP collapse. AICAR had similar effects to GYY4137 treatment while Ara-A attenuated GYY4137-mediated cardioprotection. Importantly, both GYY4137 and AICAR increased AMPK phosphorylation and decreased mTOR phosphorylation compared with the HG model group while Ara-A attenuated GYY4137-mediated AMPK phosphorylation increase and mTOR phosphorylation decrement. In conclusion, we propose that GYY4137 likely protects against HG-induced cytotoxicity by activation of the AMPK/mTOR signal pathway in H9c2 cells. © 2013 Springer Science+Business Media.


Wang Z.,Shantou University | Chen J.,Peking University | Wang S.,Fourth Peoples Hospital of Shenzhen | Chen Z.,Shantou University
Journal of Luminescence | Year: 2013

Oridonin is an effective anticancer drug which has high potency and low systemic toxicity. In this study, the interaction between oridonin and bovine serum albumin (BSA) was investigated by several spectroscopic approaches for the first time. The binding characteristics of oridonin and BSA were determined by fluorescence emission spectra and resonance light scattering spectra. It is showed that the oridonin quenches the fluorescence of BSA and the static quenching constant KSV is 1.30×104 L mol -1 at 298 K. Moreover, oridonin and BSA form a 1:1 complex with a binding constant of 0.62×104 L mol-1. On the other hand, the thermodynamic parameters indicate that the binding process was a spontaneous molecular interaction procedure, in which hydrophobic forces played a major role. The structure analysis indicates that oridonin binding results in an increased hydrophobicity around the tryptophan residues of BSA. Additionally, as shown by the UV-vis absorption, synchronous fluorescence and three-dimensional fluorescence results, oridonin could lead to conformational and some microenvironmental changes of BSA. The work provides accurate and full basic data for clarifying the binding mechanism of oridonin with BSA in vitro and is helpful for understanding its effect on protein function during its transportation and distribution in blood. © 2012 Elsevier B.V. All rights reserved.


Zhang W.,Fujian Medical University | Jia N.,Fourth Peoples Hospital of Shenzhen | Su J.,Fujian Medical University | Lin J.,Fujian Medical University | And 2 more authors.
PLoS ONE | Year: 2014

Objective: To examine in what aspects and to what extent robotic ablation is superior over manual ablation, we sought to design a meta-analysis to compare clinical outcomes between the two ablations in the treatment of atrial fibrillation. Methods and Results: A literature search was conducted of PubMed and EMBASE databases before December 1, 2013. Data were extracted independently and in duplicate from 8 clinical articles and 792 patients. Effect estimates were expressed as weighted mean difference (WMD) or odds ratio (OR) and the accompanied 95% confidence interval (95% CI). Pooling the results of all qualified trials found significant reductions in fluoroscopic time (minutes) (WMD; 95% CI; P: -8.9; -12.54 to -5.26; <0.0005) and dose-area product (Gyxcm2) (WMD; 95% CI; P: -1065.66; -1714.36 to -416.96; 0.001) for robotic ablation relative to manual ablation, with evident heterogeneity (P<0.0005) and a low probability of publication bias. In subgroup analysis, great improvement of fluoroscopic time in patients with robotic ablation was consistently presented in both randomized and nonrandomized clinical trials, particularly in the former (WMD; 95% CI; P: -12.61; -15.13 to -10.09; <0.0005). Success rate of catheter ablation was relatively higher in patients with robotic ablation than with manual ablation (OR; 95% CI; P: 3.45; 0.24 to 49.0; 0.36), the difference yet exhibiting no statistical significance. Conclusions: This study confirmed and extended previous observations by quantifying great reductions of fluoroscopic time and dose-area product in patients referred for robotic ablation than for manual ablation in the treatment of atrial fibrillation, especially in randomized clinical trials. © 2014 Zhang et al.


Xu J.,Fuzhou General Hospital of Nanjing Command | Xu J.,Fujian Medical University | Huang Y.,Fujian Medical University | Cai H.,Fujian Medical University | And 7 more authors.
PLoS ONE | Year: 2014

Objective: Currently radiofrequency and cryoballoon ablations are the two standard ablation systems used for catheter ablation of atrial fibrillation; however, there is no universal consensus on which ablation is the optimal choice. We therefore sought to undertake a meta-analysis with special emphases on comparing the efficacy and safety between cryoballoon and radiofrequency ablations by synthesizing published clinical trials. Methods and Results: Articles were identified by searching the MEDLINE and EMBASE databases before September 2013, by reviewing the bibliographies of eligible reports, and by consulting with experts in this field. Data were extracted independently and in duplicate. There were respectively 469 and 635 patients referred for cryoballoon and radiofrequency ablations from 14 qualified clinical trials. Overall analyses indicated that cryoballoon ablation significantly reduced fluoroscopic time and total procedure time by a weighted mean of 14.13 (95% confidence interval [95% CI]: 2.82 to 25.45; P = 0.014) minutes and 29.65 (95% CI: 8.54 to 50.77; P = 0.006) minutes compared with radiofrequency ablation, respectively, whereas ablation time in cryoballoon ablation was nonsignificantly elongated by a weighted mean of 11.66 (95% CI: 210.71 to 34.04; P = 0.307) minutes. Patients referred for cryoballoon ablation had a high yet nonsignificant success rate of catheter ablation compared with cryoballoon ablation (odds ratio; 95% CI; P: 1.34; 0.53 to 3.36; 0.538), and cryoballoon ablation was also found to be associated with the relatively low risk of having recurrent atrial fibrillation (0.75; 0.3 to 1.88; 0.538) and major complications (0.46; 0.11 to 1.83; 0.269). There was strong evidence of heterogeneity and low probability of publication bias. Conclusion: Our findings demonstrate greater improvement in fluoroscopic time and total procedure duration for atrial fibrillation patients referred for cryoballoon ablation than those for radiofrequency ablation. © 2014 Xu et al.


Han W.-D.,Fourth Peoples Hospital of Shenzhen | Huang A.-J.,Fourth Peoples Hospital of Shenzhen | Chen L.-P.,Second Peoples Hospital of Futian District
Chinese Journal of Tissue Engineering Research | Year: 2013

Background: Bone cement injection is one of the commonly used methods for the treatment of thoracolumbar osteoporotic fractures. Objective: To evaluate biomechanical properties and fixed effects of bone cement injection for the treatment of thoracolumbar osteoporotic fractures. Methods: The specimens of thoracolumbar osteoporotic fractures were selected, and used to measure the mechanical properties of bone mineral density, maximum pressure load, displacement and stiffness. The bone model was established, and after bone cement injection, the maximum pressure load, displacement and stiffness were measured again. The mechanical properties before and after bone cement injection were compared, and compared with those in the treatment of thoracolumbar osteoporotic fractures with pedicle screw fixation. The patients received bone cement injection for the treatment of thoracolumbar osteoporotic fractures were followed-up, and the treatment effect of bone cement injection was determined through evaluating the pain relief degree, thoracolumbar vertebral height restoration, amount of bone cement injection and bone cement extravasation. Results and Conclusion: The biomechanical experiment determined that the maximum load was 2 285 N after thoracolumbar osteoporotic fractures treated with bone cement injection, which increased almost by 16.9% than 1 954 N before fracture; the stiffness was 427 N after thoracolumbar osteoporotic fractures treated with bone cement injection, which increased almost by 22.1% than 349 N before fracture, and showed good biological properties. The thoracolumbar osteoporotic fractures patients treated with bone cement injection and closed reduction combined with bone cement injection were followed-up, and found that both these two methods could relieve the pain of the patients. But closed reduction combined with bone cement injection for the treatment of thoracolumbar osteoporotic fractures was better than bone cement injection in the amount of bone cement injection, local kyphosis angle and vertebral height restoration. The results indicate that closed reduction combined with bone cement injection is a safe and effective method for the treatment of thoracolumbar osteoporotic fractures.


Wang J.,Fourth Peoples Hospital of Shenzhen Futian Peoples Hospital | Xu J.,Fourth Peoples Hospital of Shenzhen Futian Peoples Hospital | Chen J.,Fourth Peoples Hospital of Shenzhen Futian Peoples Hospital | He Q.,Fourth Peoples Hospital of Shenzhen Futian Peoples Hospital | And 4 more authors.
Archives of Gynecology and Obstetrics | Year: 2010

Objectives: Photodynamic therapy (PDT) is a minimally invasive treatment for cervical intraepithelial neoplasia. The purpose of this study was to assess the feasibility and effectiveness of PDT in patients with CIN and high-risk HPV infection. Methods: Five patients diagnosed CIN 2 or CIN 3 with human papillomavirus (HPV) infection were included. Each patient had gynecologic examination including cervical cytology, HPV DNA testing, colposcopy and biopsy. Two grams of 5-aminolevulinic acid (ALA) gel (118 mg/g) was topically applied to the cervix and covered with a special plastic cap for 3-4 h, followed by 20 min illumination of both ecto- and endo-cervical canal with red coherent light (wavelength 633 nm) using a PDT laser and a special light catheter. The PDT therapy was repeated with an interval of 1 week. Follow-up examination including biopsy and histology, colposcopy, HPV DNA testing were carried out after 3, 6 and 9 months. Results: Treatment could be accomplished in all cases and no severe side effect was encountered. All the CIN2 patients had a complete response for 9 months and one CIN3 HPV remained positive for 6 months after three or four treatments. Conclusion: PDT seems to be a non-invasive, repeatable procedure for CIN and cervical HPV infection with minimal side effects and can be easily performed on outpatient basis. © Springer-Verlag 2009.


Long B.,Fourth Peoples Hospital of Shenzhen | Long B.,Shenzhen Institute of Geriatrics | Long B.,Second Peoples Hospital of Shenzhen | Zhang J.,Tsinghua University | And 4 more authors.
Organic and Biomolecular Chemistry | Year: 2016

Wewakazole B is a novel cyclodecapeptide with highly potent cytotoxic activity isolated from a sample of M. producens collected from the Red Sea. It contains nine common and three modified amino acid residues. The first total synthesis of Wewakazole B was successfully achieved on a gram scale, unambiguously confirming its structure. Notable features include the careful choice of amino acid-protecting groups and the construction of three different substituted oxazoles present in this natural product. © The Royal Society of Chemistry 2016.


Zhou L.,East China University of Science and Technology | Qian J.,East China University of Science and Technology | Liu J.,East China University of Science and Technology | Zhao R.,Fourth Peoples Hospital of Shenzhen | And 2 more authors.
European Journal of Mass Spectrometry | Year: 2016

Amyloid-β (Aβ)-degrading enzyme neprilysin (NEP) plays a pivotal role in eliminating Aβ. The oxidized modification of NEP by 4-hydroxy-2-nonenal (HNE) may reduce the clearance of Aβ in cultured cells and Alzheimer's disease (AD) brains. The aim of this research is to study whether HNE could modify the NEP protein and identify the specific sites of HNE-NEP modification using a linear trap quadrapole (LTQ) Velos Pro-Orbitrap Elite mass spectrometer. NEP activity was determined after SH-SY5Y cells had incubated with HNE (20 μM) for 24 hours. To identify the sites of NEP modification, samples of both native and HNE-modified NEP digested by trypsin were analyzed using a LTQ Velos Pro-Orbitrap Elite mass spectrometer. The NEP peptide-sequence information from the fragment ion masses was used to search for the sites of NEP adduction. HNE-treated cells showed a 60% loss of NEP activity. NEP was covalently adducted at Lys 93, Lys 472 by HNE via Michael addition. Compared to the control group, the sites of modified peptide in NEP showed a consistent 156 Da increased in m/z, which provides sequence information and might contribute to further studies on drug design and the therapeutics of AD. © 2016 IM Publications LLP. All rights reserved.


Zuo W.,Fourth Peoples Hospital of Shenzhen | Zhu Y.-Y.,Fourth Peoples Hospital of Shenzhen | Yu H.-T.,Fourth Peoples Hospital of Shenzhen | Li H.-L.,Fourth Peoples Hospital of Shenzhen | And 2 more authors.
International Eye Science | Year: 2014

AIM: To discuss the functional significance of purine receptor P2X7 in retinal capillary pericytes rats. METHODS: The TUNEL test was applied to observe the survival rate of normal retinal capillary pericytes and diabetic retinal capillary pericytes which were affected by P2X7 agonist BzATP and antagonist OxATP in microscopy. RESULTS: Activation of P2X7 receptors caused occurence of apoptosis in retinal capillary pericytes. Compared with normal retinal capillary pericytes, when they were at the same concentration or time, the diabetic retinal capillary pericytes caused much more apoptosis than normal retinal capillary pericytes. The antagonist OxATP could significantly reduce the toxic effects activated by BzATP, and then increased the livability of retinal capillary pericytes. CONCLUSION: The activity of P2X7 receptor plays a regulatory role on RPC apoptosis.

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