Yangzhou First Peoples Hospital
Yangzhou First Peoples Hospital
Guo L.,Jilin University |
Yin A.,Yangzhou First Peoples Hospital |
Zhang Q.,Shaanxi University of Chinese Medicine |
Zhong T.,North Dakota State University |
And 2 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2017
The objectives of the present study were to investigate the effect of ANG-(1-7) on the development of cardiac hypertrophy and to identify the intracellular mechanism underlying this action of ANG-(1-7). Blood pressure and heart rate were recorded using radiotelemetry before and after chronic subcutaneous infusion of control (PBS), ANG II, ANG-(1-7), or ANG II _ ANG-(1-7) for 4 wk in normotensive rats. Chronic administration of ANG-(1-7) did not affect either basal blood pressure or the ANG II-induced elevation in blood pressure. However, ANG-(1-7) significantly attenuated ANG II-induced cardiac hypertrophy and perivascular fibrosis in these rats. These effects of ANG-(1-7) were confirmed in cultured cardiomyocytes, in which ANG-(1-7) significantly attenuated ANG II-induced increases in cell size. This protective effect of ANG-(1-7) was significantly attenuated by pretreatment with A779 (a Mas receptor antagonist) or Mito-TEMPO (a mitochondriatargeting superoxide scavenger) as well as blockade of Sirt3 (a deacetylation-acting protein) by viral vector-mediated overexpression of sirtuin (Sirt)3 short hairpin (sh)RNA. Western blot analysis demonstrated that treatment with ANG-(1-7) dramatically increased Sirt3 expression. In addition, ANG-(1-7) attenuated the ANG II-induced increase in mitochondrial ROS generation, an effect that was abolished by A779 or Sirt3 shRNA. Moreover, ANG-(1-7) increased FoxO3a deacetylation and SOD2 expression, and these effects were blocked by Sirt3 shRNA. In summary, the protective effects of ANG-(1-7) on ANG II-induced cardiac hypertrophy and increased mitochondrial ROS production are mediated by elevated SOD2 expression via stimulation of Sirt3-dependent deacetylation of FoxO3a in cardiomyocytes. Thus, activation of the ANG-(1-7)/Sirt3 signaling pathway could be a novel therapeutic strategy in the management of cardiac hypertrophy and associated complications. NEW & NOTEWORTHY Chronic subcutaneous ANG-(1-7) has no effect on ANG II-induced elevations in blood pressure but significantly attenuates ANG II-induced cardiac hypertrophy and fibrosis by a mitochondrial ROS-dependent mechanism. This protective effect of ANG-(1-7) against the action of ANG II action is mediated by stimulation of sirtuin-3-mediated deacetylation of FoxO3a, which triggers SOD2 expression. © 2017 the American Physiological Society.
Xu Y.,Shanghai JiaoTong University |
Li Q.,Shanghai JiaoTong University |
Li X.-Y.,Yangzhou First Peoples Hospital |
Yang Q.-Y.,Shanghai JiaoTong University |
And 2 more authors.
Journal of Experimental and Clinical Cancer Research | Year: 2012
Background: Antiangiogenic therapy is one of the most significant advances in anticancer treatment. The benefits of antiangiogenic therapies of late-stage cancers have been investigated but are still too limited. Methods. We used an ovarian cancer model to test the effect of short-term bevacizumab treatment on metastasis as measured by bioluminescence. Western blotting and CD34-PAS dual staining were performed to assess hypoxia-inducible transcription factor-1 (HIF-1) expression and vasculogenic mimicry(VM) formation. Cell viability was examined by a CCK8 assay. Results: Bevacizumab demonstrated antitumor effects in models of ovarian cancer, but also accelerated metastasis together, with marked hypoxia and VM formation in mice receiving short-term therapy. Bevacizumab treatment did not affect SKOV3 cell viability and the amount of VM in three-dimensional culture. Conclusion: These results suggest that antiangiogenic therapy may potentially influence the progression of metastatic disease, which has been linked to the hypoxic response and VM formation. © 2012 Yuan et al; licensee BioMed Central Ltd.
Zhang H.,Nanjing Medical University |
Jin G.,Nanjing Medical University |
Li H.,Nanjing Medical University |
Ren C.,Northern Jiangsu Peoples Hospital |
And 7 more authors.
Carcinogenesis | Year: 2011
Two recent genome-wide association studies reported significant associations of genetic variants at 1q22, 10q23 and 20p13 with gastric cancer (GC) risk in Chinese populations. However, these findings have not been confirmed in other independent studies. Here, we performed an independent case-control study in a Chinese population by genotyping three loci (rs4072037A>G at 1q22, rs2274223A>G at 10q23 and rs13042395C>T at 20p13) in 1681 GC cases and 1858 controls. We found that rs4072037 at 1q22 and rs2274223 at 10q23 were significantly associated with risk of GC with per allele odds ratio (OR) of 0.72 [95% confidence interval (CI): 0.63-0.81; P 5 2.98 3 1027] and 1.42 (95% CI: 1.27-1.58;P 5 9.68 3 10210), respectively. The association was more prominent for rs2274223 in female (OR 5 1.86, 95% CI: 1.49-2.32) and gastric cardia adenocarcinoma (GCA) (OR 5 1.71, 95% CI: 1.49-1.95). Furthermore, we combined the two single-nucleotide polymorphisms to evaluate the joint effect and found that the GC risk significantly increased with the number of risk allele increasing with a trend P value of 6.66 3 10-16, and individuals with four risk alleles had a 3.28-fold (95% CI: 1.75-6.13) risk of GC compared with those having no risk alleles. However, no significant association was detected between rs13042395 at 20p13 and GC risk (OR 5 1.04, 95% CI: 0.94-1.15; P 5 0.452). In conclusion, our results indicate that genetic variants at 1q22 and 10q23 but not 20p13 may serve as candidate markers for GC susceptibility in the Chinese population. © The Author 2011. Published by Oxford University Press.
Zhu C.,Nanjing Medical University |
Ren C.,Nanjing Medical University |
Ren C.,Northern Jiangsu Peoples Hospital |
Han J.,Nanjing Medical University |
And 9 more authors.
British Journal of Cancer | Year: 2014
Background: Circulating microRNAs (miRNAs) have been implicated as novel biomarkers for gastric cancer (GC) diagnosis. However, the mixture of GC subtypes may have led to the inconsistent circulating miRNA profiles, and the clinical performance of circulating miRNAs has not yet been evaluated independently on early detection of GC. Methods: A four-phase study was designed with a total of 160 cancer-free controls, 124 patients with gastric non-cardia adenocarcinoma (GNCA) and 36 patients diagnosed gastric cardia adenocarcinoma (GCA). In the discovery phase, we screened the miRNA expression profile in plasma of 40 GNCA patients (stage I) and 40 matched controls by TaqMan low density array (TLDA) chips with pooled samples. Differentially expressed miRNAs were further validated in individual sample using quantitative reverse-transcriptase PCR (qRT-PCR) in the training phase. Subsequently, in an independent validation phase, the identified miRNAs were evaluated in 48 GNCA patients (stage I) and 102 matched controls. Finally, the identified miRNAs were further assessed in an external validation phase including advanced GNCA and GCA patients. Additionally, the expression levels of identified miRNAs were measured in the media of BGC823 and MGC803 cell lines. Results: Five miRNAs (miR-16, miR-25, miR-92a, miR-451 and miR-486-5p) showed consistently elevated levels in plasma of the GC patients as compared with controls, and were identified to be potential markers for GNCA with area under the receiver operating characteristic (ROC) curves (AUCs) ranging from 0.850 to 0.925 and 0.694 to 0.790 in the training and validation phases, respectively. The five-miRNA panel presented a high diagnostic accuracy for the early-stage GNCA (AUCs=0.989 and 0.812 for the training and validation phases, respectively). Three miRNAs (miR-16, miR-25 and miR-92a) were excreted into the culture media of GC cell lines. Conclusions: The five-miRNA panel in plasma may serve as a potential non-invasive biomarker in detecting the early-stage GC.© 2014 Cancer Research UK. All rights reserved.
Tan W.,Nantong University |
Tan W.,Yangzhou First Peoples Hospital |
Gu Z.,Nantong University |
Shen B.,Nantong University |
And 6 more authors.
Journal of Cellular Biochemistry | Year: 2015
Recent studies showed that allogeneic bone marrow (BM)-mesenchymal stem cells transplantation (MSCT) was effective in systemic lupus erythematosus (SLE) patients and lupus-prone mice. However, syngeneic BM-MSCT was ineffective. Previous studies, including ours, revealed that BM-MSCs from SLE patients exhibited early signs of senescence and apoptosis such as slow proliferation, increasing senescence-associated β-galactosidase (SA-β-gal)-positive cells and Annexin V-positive cells, and caspase cascade activation. The abnormalities of BM-MSCs might be associated with the pathogenesis of SLE. In this study, we aimed to determine the molecular mechanism of senescent BM-MSCs from SLE patients. We found that the expression of protein 27 kinase inhibition protein 1(p27kip1) increased significantly, which was regulated by phosphatase and tensin homology deleted on chromosome 10 (PTEN)/protein kinase B (Akt) signaling in SLE BM-MSCs. Knockdown of PTEN or p27kip1 could reverse the senescent features of BM-MSCs via down-regulating p27kip1 expression. When purified CD4+ T cells were incubated with PTEN or p27kip1-silenced SLE BM-MSCs, the ratio of regulatory T (Treg)/T helper type 17 (Th17) cells increased significantly by enhancing regulatory cytokines (IL-10 and TGF-β) and reducing pro-inflammatory cytokines (IL-17 and IL-6). Taken together, we demonstrated that PTEN/Akt signaling played an essential role in the senescent and apoptotic BM-MSCs from SLE patients by up-regulating p27kip1 expression. J. Cell. Biochem. 116: 1583-1594, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
PubMed | Yangzhou First Peoples Hospital
Type: Journal Article | Journal: Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2015
To explore whether bariatric surgery can decrease the incidence of obesity-related tumors in obesity patients.Relevant studies comparing the incidence of obesity-related tumors in obesity patients between bariatric surgery and non- bariatric surgery were identified by search of PubMed, Medline, EBSCO, High Wire Press, OVID, EMbase, China hownet (CNKI) and Wanfang databases since the self-built database. In strict accordance with the standard after the screening, literature quality and extracted data were evaluated. Review manager 5.2 software was used to perform meta-analysis and sensitivity analysis. Inverted funnel chart was used to investigate the publication bias.Five articles including 108 954 patients were enrolled in the analysis. Among them, 26 218 cases were bariatric surgery group, and 82 736 cases of non-surgical weight loss were the control group. Meta analysis showed that bariatric surgery could obviously decrease the incidence of postoperative obesity-related tumor(RR=0.60, 95% CI:0.45-0.80, P=0.0005). Subgroup analysis showed that cancer risk difference of obesity-related tumor in male patients was not significant between two group, while the postoperative incidence of obesity-related tumor of female patients in bariatric surgery group was significantly lower compared to those female patients in control group(RR=0.68, 95% CI:0.61-0.77, P<0.01). During follow-up of 1 to 10 years, the incidence of obesity-related tumor in bariatric surgery group was significantly lower than that in control group(P<0.05). When follow-up was more than 10 years, the incidence of obesity-related tumors was similar between two groups(P=0.70).Bariatric surgery can decrease the overall risk of obesity-related cancer, especially for female patients, but with the prolongation of time, such effect of bariatric surgery is not obvious.
PubMed | Yangzhou First Peoples Hospital
Type: Journal Article | Journal: Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery | Year: 2015
To review the recent diagnosis and treatment experience with deep neck infection and emphasize the importance of radiologic evaluation, microbiology and appropriate treatment selection in these patients.A respective review was conducted in 95 cases who were diagnosed as having deep neck from Jan. 2006 to March 2015.The primary diseases in 95 patients with deep neck infection were acute tonsillitis or acute laryngitis (27 cases), infection of upper respiratory tract (23 cases), odontogenic infection or oral inflammation (16 cases), foreign bodies in esophagus (9 cases), acute cervical lymphadenitis (5 cases) and cause uncertain (15 cases). Computed tomography was performed in all of patients to identify the location, extent, and character (cellulitis in 47 cases or abscesses in 48 cases) of the infections. The locations of abscess were parapharyngeal abscess (25 cases), retropharyngeal abscess (9 cases), submaxillary space abscess (6 cases), pretracheal space abscess (5 cases) and esophageal abscess (3 cases).mediastinitis (2 cases), pericarditis (1 case), bilateral pneumothorax (2 cases), and upper digestive tract (1 case). Bacterial cultivation performed in 35 patients and positive results were detected in 21. All patients were given intravenous antibiotic therapy. Tracheotomy was performed in 4 cases. Preoperative contrast enhanced CT was performed in 42 patients and indicated the formation of abscess. Three cases with the symptoms of septic shock were transferred to ICU and one was cured. All the patients were cured except two who died of massive hemorrhage of upper digestive tract and septic shock.The airway patency in patients with deep neck infections must be ensured. Drainage may be mandatory in selected cases at presentation or in cases who fail to respond to parenteral antibiotics within the first 24-48 hours. Imaging evaluation plays a significant role in the diagnosis and rational therapeutic management in deep neck infection. Bacterial cultivation can help to make the effective treatment and provide reliable evidence for the etiopathogenisis.
PubMed | Philips, University of Washington, Yangzhou First Peoples Hospital and Biomedical Imaging Center
Type: Journal Article | Journal: PloS one | Year: 2016
Simultaneous Non-contrast Angiography and intraPlaque hemorrhage (SNAP) technique was recently proposed for joint MRA and intraplaque hemorrhage (IPH) imaging. The purpose of this study is to validate SNAPs MRA performance in patients with suspected intracranial artery disease.SNAP and time-of-flight (TOF) techniques with matched field of view and resolution were applied on 15 patients with suspected intracranial artery disease. Both techniques were evaluated based on their detection of luminal stenosis of bilateral middle cerebral arteries (MCA) and the delineation of smallest visible branches (SVB) of the MCA. Statistical analysis was conducted on the artery level.The SNAP MRA was found to provide similar stenosis detection performance when compared with TOF (Cohens 0.79; 95% Confidence Interval: 0.56-0.99). For the SVB comparison, SNAP was found to provide significantly better small artery delineation than TOF (p = 0.017). Inter-reader reproducibility for both measurements on SNAP was over 0.7. SNAP also detected IPH lesions on 13% of the patients.The SNAP techniques MRA performance was optimized and compared against TOF for intracranial artery atherosclerosis imaging and was found to provide comparable stenosis detection accuracy. Along with its IPH detection capability, SNAP holds the potential to become a first-line screening tool for high risk intracranial atherosclerosis disease evaluation.
PubMed | Yangzhou First Peoples Hospital, Nanjing University and Gothenburg University
Type: Evaluation Studies | Journal: International journal of environmental research and public health | Year: 2015
The xenoestrogens nonylphenol (NP) and bisphenol A (BPA) are regarded as endocrine disrupting chemicals (EDCs) which have widespread occurrence in our daily life. In the present study, the purpose was to analyze the combined effects of NP and BPA on the human prostate epithelial cell line RWPE-1 using two mathematical models based on the Loewe additivity (LA) theory and the Bliss independence (BI) theory. RWPE-1 cells were treated with NP (0.01-100 M) and BPA (1-5000 M) in either a single or a combined format. A cell viability assay and lactate dehydrogenase (LDH) leakage rate assay were employed as endpoints. As predicted by the two models and based on the cell viability assay, significant synergism between NP and BPA were observed. However, based on the LDH assay, the trends were reversed. Given that environmental contaminants are frequently encountered simultaneously, these data indicated that there were potential interactions between NP and BPA, and the combined effects of the chemical mixture might be stronger than the additive values of individual chemicals combined, which should be taken into consideration for the risk assessment of EDCs.
PubMed | Yangzhou First Peoples Hospital, Biomedical Imaging Center and General Hospital of the PLA Rocket Force
Type: Journal Article | Journal: Journal of magnetic resonance imaging : JMRI | Year: 2016
Basilar artery (BA) atherosclerosis is an important cause of perforator stroke in the brainstem due to plaque involvement of the perforator ostia in BA dorsal or lateral walls. Therefore, to acquire information on plaque distribution is important to better understand and prevent the perforator stroke. This study aimed to comprehensively evaluate BA plaque distribution with 3D magnetic resonance imaging (MRI) vessel wall imaging.Consecutive patients with cerebrovascular symptoms and stenosis or irregular luminal surface of BA were recruited and underwent BA 3D proton density-weighted volume isotropic turbo spin echo acquisition (VISTA) imaging at 3T. The cross-sectional and longitudinal distribution of BA plaque were analyzed with a custom-developed tool.In all, 85 BA plaques were detected in 61 recruited patients. For cross-sectional distribution, the prevalence of plaque involvement in the ventral, left, dorsal, and right quadrant of BA wall was 74.1%, 70.6%, 67.1%, and 62.4%, respectively. Of the 85 plaques, 17.7% involved one quadrant and 82.3% involved two or more quadrants. The most severe plaque region was more commonly situated at lateral walls (66.1%) as compared to ventral (23.2%, P < 0.001) and dorsal walls (10.6%, P < 0.001). Longitudinally, plaques were more frequently found to occur at BA segment distal than proximal to anterior inferior cerebellar artery (AICA) (63.5% vs. 36.5%).Taking advantage of 3D MR vessel wall imaging, BA plaques were found to more likely affect lateral walls and form in BA distal to AICA, where most perforators originate, suggesting that it might be useful to characterize BA plaque distribution before aggressive treatment for prevention of perforator stroke. J. Magn. Reson. Imaging 2016;44:1592-1599.