PubMed | Tongji University, Shanghai JiaoTong University, Johns Hopkins University, Shanghai Putuo Center Hospital and 3 more.
Type: Journal Article | Journal: Molecular & cellular proteomics : MCP | Year: 2016
We aimed to globally discover serum biomarkers for diagnosis of gastric cancer (GC). GC serum autoantibodies were discovered and validated using serum samples from independent patient cohorts encompassing 1,401 participants divided into three groups, i.e. healthy, GC patients, and GC-related disease group. To discover biomarkers for GC, the human proteome microarray was first applied to screen specific autoantibodies in a total of 87 serum samples from GC patients and healthy controls. Potential biomarkers were identified via a statistical analysis protocol. Targeted protein microarrays with only the potential biomarkers were constructed and used to validate the candidate biomarkers using 914 samples. To provide further validation, the abundance of autoantibodies specific to the biomarker candidates was analyzed using enzyme-linked immunosorbent assays. Receiver operating characteristic curves were generated to evaluate the diagnostic accuracy of the serum biomarkers. Finally, the efficacy of prognosis efficacy of the final four biomarkers was evaluated by analyzing the clinical records. The final panel of biomarkers consisting of COPS2, CTSF, NT5E, and TERF1 provides high diagnostic power, with 95% sensitivity and 92% specificity to differentiate GC patients from healthy individuals. Prognosis analysis showed that the panel could also serve as independent predictors of the overall GC patient survival. The panel of four serum biomarkers (COPS2, CTSF, NT5E, and TERF1) could serve as a noninvasive diagnostic index for GC, and the combination of them could potentially be used as a predictor of the overall GC survival rate.
Zhou C.,Shanghai JiaoTong University |
Ye L.,Shanghai JiaoTong University |
Jiang C.,Shanghai JiaoTong University |
Bai J.,Shanghai JiaoTong University |
And 2 more authors.
Tumor Biology | Year: 2015
Despite the fact that great advances have been made in the management of non-small cell lung cancer (NSCLC), the prognosis of advanced NSCLC remains very poor. HOX transcript antisense intergenic RNA (HOTAIR) has been identified as an oncogenic long noncoding RNA (lncRNA) that is involved in the progression of a variety of carcinomas and acts as a negative prognostic biomarker. Yet, little is known about the effect of HOTAIR in the hypoxic microenvironment of NSCLC. The expression and promoter activity of HOTAIR were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and luciferase reporter assay. The function of the hypoxia-inducible factor-1α (HIF-1α) binding site to hypoxia-responsive elements (HREs) in the HOTAIR promoter region was tested by luciferase reporter assay with nucleotide substitutions. The binding of HIF-1α to the HOTAIR promoter in vivo was confirmed by chromatin immunoprecipitation assay (CHIP) and electrophoretic mobility shift assay (EMSA). The effect of HIF-1α suppression by small interference RNA or YC-1 on HOTAIR expression was also determined. In the present study, we demonstrated that HOTAIR was upregulated by hypoxia in NSCLC cells. HOTAIR is a direct target of HIF-1α through interaction with putative HREs in the upstream region of HOTAIR in NSCLC cells. Furthermore, HIF-1α knockdown or inhibition could prevent HOTAIR upregulation under hypoxic conditions. Under hypoxic conditions, HOTAIR enhanced cancer cell proliferation, migration, and invasion. These data suggested that suppression of HOTAIR upon hypoxia of NSCLC could be a novel therapeutic strategy. © 2015, International Society of Oncology and BioMarkers (ISOBM).
Wang J.,Shandong University |
Wang J.,Weifang Peoples Hospital |
Wang Y.,Shanghai JiaoTong University |
Zhao D.,Tongji University |
And 2 more authors.
Renal Failure | Year: 2015
Objectives: To investigate the association between serum uric acid and mortality in a Chinese population of hypertensive patients. Methods and results: A total of 2757 Chinese hypertensive patients from department of cardiology of several hospitals in Shanghai in China were followed up for about six years in this prospective study. Mortality was recorded and related factors were evaluated. Hyperuricemia was diagnosed by serum uric acid levels of >420μmol/L in males or >357μmol/L in females. A total of 2585 hypertensive patients with complete data were included in the final statistical analysis. Totally 709 deaths (27.4%) occurred during the six-year follow-up, of which 475 deaths were attributable to cardiovascular disease (CVD). All-cause and CVD mortality of hypertensive patients with hyperuricemia was significantly higher than that of patients without hyperuricemia. The Cox regression analysis indicated that hazards ratios (HRs) of hyperuricemia for all-cause and CVD mortality were 1.206 (95% CI: 1.002-1.453) and 1.085 (95% CI: 1.002-1.271) respectively. All-cause and CVD mortality of hypertensive patients was significantly increased (both p<0.05) when uric acid levels increased. HRs of uric acid levels >536μmol/L to all-cause and CVD mortality of hypertensive patients were 2.115 (95% CI: 1.596-2.801) and 1.861 (95% CI: 1.296-2.673), respectively, compared with those of uric acid levels 357μmol/L. Conclusions: The data from this cohort study indicate that hyperuricemia can predict increased all-cause and CVD mortality in hypertensive patients. © 2015 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.
One-year clinical outcome of interventionalist-versus patient-transfer strategies for primary percutaneous coronary intervention in patients with acute st-segment elevation myocardial infarction results from the REVERSE-STEMI study
Zhang Q.,Shanghai JiaoTong University |
Yan Zhang R.,Shanghai JiaoTong University |
Qiu J.P.,Shanghai Pudong Gongli Hospital |
Zhang J.F.,Shanghai JiaoTong University |
And 7 more authors.
Circulation: Cardiovascular Quality and Outcomes | Year: 2011
Background: Traditional reperfusion options for patients with acute ST-segment elevation myocardial infarction (STEMI) presenting to non-primary percutaneous coronary intervention (PPCI)-capable hospitals generally include onsite fibrinolytics or emergency transfer for PPCIA third option, involving interventionalist transfer, was examined in the REVERSE-STEMI studyMethods and Results: A total of 334 patients with acute STEMI who presented to 5 referral hospitals with angiographic facilities but without interventionalists qualified for PPCI were randomized to receive PPCI with either an interventionalist- (n=165) or a patient-transfer (n=169) strategyThe primary end point of door-to-balloon (D2B) time and secondary end points of left ventricular ejection fraction and major adverse cardiac events (MACE) at 1-year clinical follow-up were compared between the 2 groupsCompared with the patient-transfer strategy, the interventionalisttransfer strategy resulted in a significantly shortened D2B time (median, 92 minutes versus 141 minutes; P>0.0001), with more patients having first balloon angioplasty within 90 minutes (21.2% versus 7.7%, P>0.001)This treatment strategy also was associated with higher left ventricular ejection fraction (0.60±0.07 versus 0.57±0.09, P>0.001) and improved 1-year MACE-free survival (84.8% versus 74.6%, P=0.019)Multivariate Cox proportional hazards modeling revealed that the interventionalist-transfer strategy was an independent factor for reduced risk of composite MACE (hazard ratio, 0.63; 95% CI, 0.45 to 0.88; P=0.003)Conclusions: The interventionalist-transfer strategy for PPCI may be effective in improving the care of patients with STEMI presenting to a non-PPCI-capable hospital, particularly in a congested cosmopolitan region where patient transfers could be prolonged. © 2011 American Heart Association, Inc.
PubMed | Shanghai Pudong Gongli Hospital and Shanghai JiaoTong University
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2015
Despite the fact that great advances have been made in the management of non-small cell lung cancer (NSCLC), the prognosis of advanced NSCLC remains very poor. HOX transcript antisense intergenic RNA (HOTAIR) has been identified as an oncogenic long noncoding RNA (lncRNA) that is involved in the progression of a variety of carcinomas and acts as a negative prognostic biomarker. Yet, little is known about the effect of HOTAIR in the hypoxic microenvironment of NSCLC. The expression and promoter activity of HOTAIR were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and luciferase reporter assay. The function of the hypoxia-inducible factor-1 (HIF-1) binding site to hypoxia-responsive elements (HREs) in the HOTAIR promoter region was tested by luciferase reporter assay with nucleotide substitutions. The binding of HIF-1 to the HOTAIR promoter in vivo was confirmed by chromatin immunoprecipitation assay (CHIP) and electrophoretic mobility shift assay (EMSA). The effect of HIF-1 suppression by small interference RNA or YC-1 on HOTAIR expression was also determined. In the present study, we demonstrated that HOTAIR was upregulated by hypoxia in NSCLC cells. HOTAIR is a direct target of HIF-1 through interaction with putative HREs in the upstream region of HOTAIR in NSCLC cells. Furthermore, HIF-1 knockdown or inhibition could prevent HOTAIR upregulation under hypoxic conditions. Under hypoxic conditions, HOTAIR enhanced cancer cell proliferation, migration, and invasion. These data suggested that suppression of HOTAIR upon hypoxia of NSCLC could be a novel therapeutic strategy.
Zhang L.,Fudan University |
Fu X.-H.,Shanghai Pudong Gongli Hospital |
Yu Y.,Fudan University |
Shui R.-H.,Fudan University |
And 5 more authors.
Laboratory Investigation | Year: 2015
Cathepsin B (CB) is involved in the turnover of proteins and has various roles in maintaining the normal metabolism of cells. In our recent study, CB is increased in the muscles of polymyositis/dermatomyositis (PM/DM). However, the role of CB in interstitial lung disease (ILD) has not been reported. ILD is a frequent complication of PM/DM, which is the leading cause of death in PM/DM. It carries high morbidity and mortality in connective tissue diseases, characterized by an overproduction of inflammatory cytokines and induced fibrosis, resulting in respiratory failure. The etiology and pathogenesis of ILD remain incompletely understood. This study investigated whether treatment with CA-074Me, a specific inhibitor of CB, attenuates ILD in PM. CB expression, inflammation, and fibrosis were analyzed in the lung tissues from patients with PM/DM. The animal model of PM was induced in guinea pigs with Coxsackie virus B1 (CVB1). CA-074Me was given 24 h after CVB1 injection for 7 consecutive days. At the end of the experiment, the animals were killed and lung tissues were collected for the following analysis. Inflammation, fibrosis and apoptosis cells, and cytokines were assessed by histological examinations and immunohistochemical analyses, western blot analysis and transferase-mediated dUTP nick-end labeling assay. In patients with PM/DM, the protein levels of CB were significantly elevated in lung tissues compared with healthy controls, which correlated with increases in inflammation and fibrosis. Similarly, the expression of CB, inflammation and fibrosis, CD8+ T cell, CD68+ cell, tumor necrosis factor-alpha, transforming growth factor-beta1 infiltrations, and apoptotic cell death were significantly increased in lung tissues of the guinea-pig model of CVB1-induced PM. These changes were attenuated by the administration of CA-074Me. In conclusion, this study demonstrates that PM/DM increases CB expression in lung tissues and inhibition of CB reduces ILD in a guinea-pig model of CVB1-induced PM. This finding suggests that CB may be a potential therapeutic target for ILD. © 2015 USCAP, Inc All rights reserved.
Zhang X.,Ningxia Medical University |
Wang H.,Shanghai Pudong Gongli Hospital |
Liu S.,Ningxia Medical University |
Gong P.,Shanghai Pudong Gongli Hospital |
And 4 more authors.
Journal of Cardiovascular Pharmacology and Therapeutics | Year: 2013
To compare the therapeutic effects of intensive versus moderate dosage of atorvastatin regimens in new-onset unstable angina with borderline lesions, 100 patients were randomized to receive either 80 mg/d or 20 mg/d atorvastatin for 9 months. Clinical symptoms, lipid profiles, and coronary stenosis (evaluated by coronary angiography and intravascular ultrasound) were compared to their corresponding baselines within each group and between the 2 groups after 9 months of treatment. The results showed that (1) when compared to their corresponding baselines, both groups exhibited improvement in clinical symptoms, a significant decrease in total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP; P <.01) and a significant increase in high-density lipoprotein cholesterol (HDL-C); (2) the improvement in clinical symptoms and the decrease in LDL-C and hs-CRP were significantly greater (P <.01) in the intensive-dose group than in the moderate-dose group; (3) the mean plaque volume did not progress in the intensive-dose group but increased significantly (P <.05) in the moderate-dose group. We conclude that compared to the moderate dose, the intensive-dose regimen significantly improves clinical symptoms, lowers LDL-C and hs-CRP, and halts the progression of borderline atherosclerotic plaques in patients with new-onset unstable angina. © The Author(s) 2012.
Lou Y.,Branch hospital of Shanghai First Peoples hospital |
Lu X.,Shanghai Pudong Gongli hospital |
Dang X.,University of California at San Diego
Gene Regulation and Systems Biology | Year: 2012
L-selectin plays important roles in lymphocyte homing and leukocyte rolling. Mounting evidence shows that it is involved in many disease entities including diabetes, ischemia/reperfusion injuries, inflammatory diseases, and tumor metastasis. Regulation of L-selectin at protein level has been well characterized. However, the regulation of human L-selectin transcription remains largely unknown. To address transcriptional regulation of L-selectin, we cloned 1088 bp 5′ of the start codon ATG. Luciferase analysis of the serial 5′ deletion mutants located the core promoter region at -288/-1. A major transcription initiation site was mapped at -115 by 5′RACE. Transcription factors Sp1, Ets1, Mzf1, Klf2, and Irf1 bind to and transactivate the L-selectin promoter. Significantly, FOXO1 binds to a FOXO1 motif, CCCTTTGG, at -87/-80, and transactivates the L-selectin promoter in a dose-dependent manner. Over-expression of a constitutive-active FOXO1 increased the endogenous L-selectin expression in Jurkat cells. We conclude that FOXO1 regulates L-selectin expression through targeting its promoter. © the author(s), publisher and licensee Libertas Academica Ltd.
PubMed | Fudan University, Shanghai Pudong Gongli Hospital, Shanghai Punan Hospital and East China Normal University
Type: | Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie | Year: 2016
The study was designed to evaluate the effect of ulinastatin on the permeability of the blood-brain barrier in rats with global cerebral ischemia/reperfusion injury using MRI. A total of 108 Wistar rats (240 g-280g) were randomly divided into three groups (n=36): sham group (S group), global cerebral ischemia/reperfusion model group (GCI/R group) and 10,000U/kg ulinastatin intervention group (U group). Fifty-four Wistar rats were used for MRI, and the rest were used for Evans Blue(EB)analysis. We used the Pulsinelli four-vessel occlusion (4-VO) model of global cerebral ischemia/reperfusion to investigate the integrity of the blood-brain barrier with Evans Blue (EB) staining at 15min after ischemia and at 6h (n=6), 24h (n=6), and 48h (n=6) after reperfusion to assess blood-brain barrier permeability with MRI. In the ulinastatin treatment group, the area of EB staining was significantly smaller, the exudation of EB decreased significantly after cerebral ischemia/reperfusion at 6h, 24h, 48h, compared to the model group at corresponding time points (P<0.05) but increased compared to the sham group. The model group exhibited significantly highlighted regions of Gd-DTPA after post-contrast at the corresponding areas and time points compared with the sham group (P<0.05). The highlighted regions of Gd-DTPA in the ulinastatin treatment group were significantly higher compared with those of the sham group but lower when compared with those of the model group (P<0.05). The integrity of the blood-brain barrier after cerebral ischemia/reperfusion injury was damaged. Ulinastatin could significantly improve the permeability of the blood-brain barrier after cerebral ischemia/reperfusion injury in rats.
PubMed | Shanghai Pudong Gongli Hospital
Type: Journal Article | Journal: Molecular medicine reports | Year: 2015
The aim of the present study was to investigate the underlying molecular mechanisms of osteoporosis and to identify novel candidate genes involved in this disease. The gene expression profile of GSE35958 was downloaded from Gene Expression Omnibus, including five samples of human mesenchymal stem cells from patients with osteoporosis and four control samples. Differentially expressed genes (DEGs) were initially identified following an analysis using Students t-test. Subsequently, a protein-protein interaction (PPI) network of the significant pathways was constructed, based on the Human Protein Reference Database. In the significant pathways, DEGs were screened using cut-off criteria of FDR<0.1 and |log(2)FC|>1.5. A co-change network for pathways was also constructed using the method of cumulative hypergeometric probability distribution. Finally, the transcriptional regulatory network for DEGs was constructed based on the TRANSFAC database. In total, 1,127 DEGs, including 554 upregulated and 573 downregulated DEGs, were screened. The constructed PPI network for the DEGs involved in the two significant pathways, including focal adhesion and lysosome, demonstrated that the five DEGs with a high degree (>60) were -catenin, SHC-transforming protein 1, RAC- serine/threonine-protein kinase, caveolin 1 and filamin A, with degrees of 135, 117, 117, 73 and 63, respectively. The pathway with the degree of 22 in the constructed co-change network was neuroactive ligand receptor interaction. The nine genes with a high ( 9) degree in the constructed transcriptional regulatory network were REL-associated protein, upstream stimulatory factor 1, specificity protein 1, Fos-related antigen 1, cyclin-dependent kinase inhibitor 1A, upstream stimulatory factor 2, ETS domain-containing protein Elk1, JUND and retinoic acid receptor , with degrees of 29, 27, 19, 18, 17, 13, 11, 11 and 9, respectively. The DEGs with high degree in the PPI and transcriptional regulatory networks may be candidate target molecules, which may be used to monitor, diagnose and treat osteoporosis.