Zhang H.,Shenyang Northern Hospital |
Han Y.,Shenyang Northern Hospital |
Tao J.,Shenyang Northern Hospital |
Liu S.,Shenyang Northern Hospital |
Yan C.,Shenyang Northern Hospital
Experimental Cell Research | Year: 2011
The migration of vascular endothelial cells plays a critical role in a variety of vascular physiological and pathological processes, such as embryonic development, angiogenesis, wound healing, re-endothelialization, and vascular remodeling. This study clarified the role and mechanism of a new vascular homeostasis regulator, Cellular repressor of E1A-stimulated genes (CREG), in the migration of primary human umbilical vein endothelial cells (HUVECs). A wound healing assay and transwell migration model showed that upregulation of CREG expression induced HUVEC migration and it was positively correlated with the expression of vascular endothelial growth factor. Furthermore, wild type integrin-linked kinase reversed the poor mobility of CREG knock-down HUVECs; in contrast, kinase-dead integrin-linked kinase weakened the migration of HUVECs. We also studied the effect of CREG on HUVEC migration by the addition of an mTOR inhibitor, recombinant vascular endothelial growth factor 165, neutralizing antibody of vascular endothelial growth factor 165 and AKT siRNA, and we concluded that CREG induces endothelial cell migration by activating the integrin-linked kinase/AKT/mTOR/VEGF 165 signaling pathway. © 2011 Elsevier Inc.
Han Y.,Shenyang Northern Hospital |
Zhu G.,WuHan Asia Heart Hospital |
Han L.,CangZhou Central Hospital |
Hou F.,Changchun Central Hospital |
And 19 more authors.
Journal of the American College of Cardiology | Year: 2014
Objectives This study sought to evaluate the safety and efficacy of rosuvastatin in preventing contrast-induced acute kidney injury (CI-AKI) in patients with diabetes mellitus (DM) and chronic kidney disease (CKD). Background CI-AKI is an important complication after contrast medium injection. While small studies have shown positive results with statin therapy, the role of statin therapy in prevention of CI-AKI remains unknown. Methods We randomized 2,998 patients with type 2 DM and concomitant CKD who were undergoing coronary/peripheral arterial angiography with or without percutaneous intervention to receive rosuvastatin, 10 mg/day (n = 1,498), for 5 days (2 days before, and 3 days after procedure) or standard-of-care (n = 1,500). Patients' renal function was assessed at baseline, 48 h, and 72 h after exposure to contrast medium. The primary endpoint of the study was the development of CI-AKI, which was defined as an increase in serum creatinine concentration ≥0.5 mg/dl (44.2 μmol/l) or 0.25% above baseline at 72 h after exposure to contrast medium. Results Patients randomized to the rosuvastatin group had a significantly lower incidence of CI-AKI than controls (2.3% vs. 3.9%, respectively; p = 0.01). During 30 days' follow-up, the rate of worsening heart failure was significantly lower in the patients treated with rosuvastatin than that in the control group (2.6% vs. 4.3%, respectively; p = 0.02). Conclusions Rosuvastatin significantly reduced the risk of CI-AKI in patients with DM and CKD undergoing arterial contrast medium injection. (Rosuvastatin Prevent Contrast Induced Acute Kidney Injury in Patients With Diabetes [TRACK-D]; NCT00786136).
A prospective, multicenter, randomized trial of paclitaxel-coated balloon versus paclitaxel-eluting stent for the treatment of drug-eluting stent in-stent restenosis: Results from the PEPCAD China ISR trial
Xu B.,Fu Wai Hospital |
Gao R.,Fu Wai Hospital |
Wang J.,Zhejiang University |
Yang Y.,Fu Wai Hospital |
And 8 more authors.
JACC: Cardiovascular Interventions | Year: 2014
Objectives The intention of the PEPCAD China ISR (A Prospective, Multicenter, Randomized Trial of Paclitaxel-Coated versus Paclitaxel-Eluting Stent for the Treatment of Drug-Eluting Stent In-Stent Restenosis) was to demonstrate the efficacy of paclitaxel-coated balloon (PCB) angioplasty in a non-European patient population with coronary drug-eluting stent in-stent restenosis (DES-ISR). Background The treatment of DES-ISR is still challenging with no established best strategy. Moreover, there is no study on the effect of PCB in the treatment of ISR in the Chinese population. Methods PEPCAD China ISR was a 220-patient randomized (1:1), single-blind prospective multicenter trial conducted in China. Patients with coronary DES-ISR received either PCB (SeQuent Please, B. Braun Melsungen AG, Melsungen, Germany) or paclitaxel-eluting stent (Taxus Liberté, Boston Scientific, Natick, Massachusetts) treatment. The primary endpoint was in-segment late lumen loss at 9 months. Results There were no significant baseline differences between both treatment groups in terms of patient, lesion, or procedural characteristics. At 9 months, in-segment late lumen loss in the PCB group was noninferior to that of the paclitaxel-eluting stent group (0.46 ± 0.51 mm vs. 0.55 ± 0.61 mm; difference: -0.06 mm with 95% confidence interval: -0.23 to 0.10; p for noninferiority = 0.0005). The 9-month rate of binary restenosis and 12-month composite clinical event rates were not significantly different between groups. Conclusions In a randomized trial of 220 patients, angioplasty with a PCB was noninferior to paclitaxel-eluting stent implantation when used to treat DES-ISR. On the basis of these, as well as previous randomized trial data, PCB angioplasty offers an effective treatment for DES-ISR without the necessity of implanting additional metal layers for drug release. © 2014 by the American College of Cardiology Foundation.
Du Z.-X.,Shenyang University |
Yan Y.,Shenyang University |
Yan Y.,Shenyang Northern Hospital |
Zhang H.-Y.,Shenyang University |
And 5 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011
Context: Our previous data showed that reactive oxygen species generation might be ascribed to the cytotoxic response of thyroid cancer cells to proteasome inhibition and the ability of cancer cells to induce catalytic subunit for glutamate cysteine ligase (GCLC) and subsequent production of glutathione, thereby scavenging reactive oxygen species was partly ascribed to the cytotoxic responses of thyroid cancer cells to proteasome inhibition. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor responsible for transcriptional activation of various cytoprotective genes including GCLC. Objective: The purpose of this study was to determine the involvement of Nrf2 in GCLC induction and cytotoxicity of thyroid cancer cells mediated by proteasome inhibition. Design: The effects of proteasome inhibition on the expression and distribution of Nrf2 were analyzed using immunocytochemistry and Western blot. To ascertain the effect of Nrf2 and p38 MAPK, cells were transfected with Nrf2 plasmid or small interfering RNA against Nrf2 or p38MAPK. Apoptotic cells, production of glutathione, and induction of GCLC mediated by proteasome inhibition were investigated using flow cytometry, spectrophotometry, and real-time RT-PCR, respectively. Results: Proteasome inhibition caused accumulation and nuclear translocation of Nrf2, which compromised the cytotoxic effects of proteasome inhibition, at least in part, via induction of GCLC. In addition, nuclear translocation of Nrf2 was p38 MAPK dependent, and p38 MAPK inhibition augmented the cytotoxic effects of proteasome, at least partly, via suppression of transactivation of Nrf2. Conclusions: These studies support the hypothesis that proteasome inhibitors activate an antiapoptotic survival program through p38 MAPK that involves transcriptional activity of Nrf2. Copyright © 2011 by The Endocrine Society.
Yang L.,Shenyang Pharmaceutical University |
Guo T.,Shenyang Northern Hospital |
Xia D.-Y.,Shenyang Northern Hospital |
Zhao L.-S.,Shenyang Pharmaceutical University
Journal of Clinical Pharmacy and Therapeutics | Year: 2012
What is known and Objective: Interethnic variability in drug pharmacokinetics is well known. Our aim was to investigate whether the pharmacokinetics of losartan and its active carboxylic acid metabolite E-3174 vary between subjects of five Chinese ethnicities (Han, Mongolian, Korean, Hui and Uigur). Methods: Fifty healthy subjects (five men and five women of each ethnicity) were recruited, and each received 50-mg dose of losartan in tablet form. Fourteen blood samples were collected for each subject over a 24-h period after drug administration. The concentrations of losartan and its active carboxylic acid metabolite E-3174 in plasma were determined by high-performance liquid chromatography/fluorescence (HPLC/FLU) method, and the pharmacokinetic parameters were calculated by DAS 2.0 software and compared by SPSS 16.0 software. Pharmacokinetic parameters, including area under the curve from 0 h to the last measured point 24 h [AUC(0-24)], area under the curve from 0 h to infinite time [AUC(0-∞)], peak plasma concentration (Cmax), time to reach Cmax (tmax), oral clearance (CL), oral volume of distribution (Vd) and elimination half-life (t1/2), were determined following a single oral dose of losartan. Results and Discussion: The t1/2 values of losartan and its active carboxylic acid metabolite E-3174 showed significant differences across the five ethnicities. After normalization by weight, no ethnicity-based difference was noted in the pharmacokinetic parameters of losartan. However, there were significant differences in Cmax and Vd of the active carboxylic acid metabolite E-3174 for Han and Mongolian subjects, compared with the other three ethnic groups. There was a high linear correlation between weight and Cmax, AUC(0-24), AUC(0-∞), CL and Vd. What is new and Conclusion: Ethnicity was associated with significant differences in the single-dose pharmacokinetics of losartan's active carboxylic acid metabolite E-3174 in healthy subjects of the five main ethnic groups in China. © 2011 Blackwell Publishing Ltd.
Wu X.,Liaoning University of Traditional Chinese Medicine |
Wu X.,Shenyang Northern Hospital |
Yuan L.,Economic and Technological Development Zone Public Security Bureau of Shenyang |
Zuo J.,Tianjin Medical University |
And 2 more authors.
European Journal of Clinical Pharmacology | Year: 2014
Purpose: Codeine is an analgesic drug acting on μ-opioid receptors predominantly via its metabolite morphine formed almost exclusively by CYP2D6. Genetic polymorphisms in CYP2D6 are associated with diminished pain relief and/or severe opioid side effects. In Chinese individuals, CYP2D6*10 is the most common allele with reduced enzyme activity. In this study, we investigated the effect of this allele on the pharmacokinetics of codeine and its metabolites. Method: A blood sample was collected from healthy Mongolian volunteers for CYP2D6 genotyping using a PCR-RFLP assay. A pharmacokinetic study was then carried out in three groups with CYP2D6*1/*1 (n = 10), CYP2D6*1/*10 (n = 10) and CYP2D6*10/*10 (n = 9) genotypes by collecting serial blood samples for determination of plasma levels of codeine and its metabolites, morphine, morphine 3-glucuronide (M3G) and morphine 6-glucuronide (M6G) before and after a single 30-mg oral dose of codeine phosphate. Codeine and its metabolites were measured by LC-MS/MS. Results: No significant differences were observed in the pharmacokinetic parameters of codeine in the three genotype groups. However, the C max and AUC0-∞ of morphine, M3G and M6G were significantly different between the study groups (P < 0.05). Compared with the*1/*1 group, the AUC0-∞ for morphine in the*1/*10 and*10/*10 groups decreased by ratios (95 % CI) of 0.93 (0.26-1.59) and 0.494 (0.135-0.853) respectively. Corresponding ratios for M3G were 0.791 (0.294-1.288) and 0.615 (0.412-0.818) and for M6G were 0.643 (0.39-0.957) and 0.423 (0.267-0.579). Conclusion: This study demonstrates that the CYP2D6*10 allele plays an important role in the pharmacokinetics of the O-demethylated metabolites of codeine after oral administration. © 2013 Springer-Verlag Berlin Heidelberg.
Liang Z.-Y.,Shenyang Northern Hospital |
Han Y.-L.,Shenyang Northern Hospital |
Zhang X.-L.,Shenyang Northern Hospital |
Li Y.,Shenyang Northern Hospital |
And 2 more authors.
EuroIntervention | Year: 2013
Aims: The current study sought to evaluate the clinical impact of newly reported genetic variations and their association with clopidogrel high on-treatment platelet reactivity (HTPR) in acute coronary syndrome (ACS) patients after drug-eluting stent (DES) implantation. Methods and results: The study enrolled 1,016 consecutive patients with ACS undergoing DES implantation. A total of 19 tag single nucleotide polymorphisms (SNPs) were selected from CYP3A4/5, CYP2C19, P2Y12 and ABCB1 genes. ADP-induced light transmittance aggregometry (LTA) was performed to test the post-procedure maximum platelet agglutination (MPA). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction (MI), stent thrombosis, and ischaemic stroke at one-year follow-up after DES placement. The secondary endpoint was the incidence of bleeding events. The post-procedure MPA was calculated and the cut-off point was determined for the HTPR. Using multivariate logistic regression analysis, the carriage of two CYP2C19 LOF alleles was an independent predictor of the post-procedure HTPR (OR: 2.8, 95% CI: 1.70-7.23, p<0.001). Through multivariate Cox regression analysis, the carriage of two CYP2C19 LOF alleles and the post-procedure HTPR were independent predictors of the primary endpoint (HR: 2.3, 95% CI: 1.40-4.97, p<0.001; HR: 2.9, 95% CI: 1.52-5.57, p<0.001, respectively). However, post-procedure MPA did not predict a bleeding event (HR: 0.9, 95% CI: 0.44-1.59, p=0.532). Conclusions: In patients with ACS, the CYP2C19 LOF allele was associated with post-procedure HTPR and a subsequently increased risk of adverse clinical events at one-year follow-up following DES implantation and clopidogrel administration. © Europa Digital and Publishing 2013. All rights reserved.
Cao P.,Shenyang Northern Hospital |
Liang Y.,Shenyang Northern Hospital |
Gao X.,Shenyang Northern Hospital |
Zhao M.-G.,Shenyang Northern Hospital |
Liang G.-B.,Shenyang Northern Hospital
CNS Neuroscience and Therapeutics | Year: 2013
Summary: Aims: The MS-275 is a selective inhibitor of class I histone deacetylases (HDACs), which has been reported as a potential strategy in some central nervous system diseases associated with neurodegeneration and disturbed learning. However, its role in traumatic brain injury is not well defined. In this study, we examined the behavioral-cognitive performance as well as histology outcome in adult rats to evaluate whether postinjury administration of MS-275 (15 and 45 mg/kg) would provide neuroprotection benefits and ameliorate cognitive deficits following fluid percussion injury. Methods: Traumatic brain injury (̃2.15 ATMs) was produced using a fluid percussion device with the lateral orientation. MS-275 was administered (15 and 45 mg/kg) systemically once daily for 7 days starting at 30 min after lateral fluid percussion TBI. Acquisition of spatial learning and memory retention was assessed using the Morris water maze (MWM) on days 10-14 after TBI. Brain tissues were collected and stained with Fluoro-Jade B histofluorescence (for degenerating neurons) at 24 h after injury and cresyl violet (for long-term neuronal survival) on day 14 postinjury. Results: Behavioral outcome after TBI revealed MS-275 treatment groups, at all doses examined, performed significantly better in the Morris Water Maze (P < 0.001). Acute histology analysis demonstrated that 45 mg/kg MS-275 significantly reduced the number of degenerating neurons in the ipsilateral CA2-3 hippocampus at 24 h postinjury (P = 0.007). There was a trend for MS-275 to increase the survival of neurons in the CA2-3 hippocampus on 14 days after TBI (P = 0.164). Conclusion: Our present data highlight the fact that MS-275 may provide neuroprotective effect and improve cognitive performance after TBI. We concluded that MS-275 is a potential novel treatment and will have an ameliorative effect on some of the pathological features associated with TBI. © 2013 Blackwell Publishing Ltd.
Wang H.-S.,Shenyang Northern Hospital |
Wang Z.-W.,Shenyang Northern Hospital |
Yin Z.-T.,Shenyang Northern Hospital
PLoS ONE | Year: 2014
Background: Postoperative atrial fibrillation (POAF) remains the most common complication after cardiac surgery. Current guidelines recommend β-blockers to prevent POAF. Carvedilol is a non-selective β-adrenergic blocker with anti-inflammatory, antioxidant, and multiple cationic channel blocking properties. These unique properties of carvedilol have generated interest in its use as a prophylaxis for POAF. Objective: To investigate the efficacy of carvedilol in preventing POAF. Methods: PubMed from the inception to September 2013 was searched for studies assessing the effect of carvedilol on POAF occurrence. Pooled relative risk (RR) with 95% confidence interval (CI) was calculated using random- or fixed-effect models when appropriate. Six comparative trials (three randomized controlled trials and three nonrandomized controlled trials) including 765 participants met the inclusion criteria. Results: Carvedilol was associated with a significant reduction in POAF (relative risk [RR] 0.49, 95% confidence interval [CI] 0.37 to 0.64, p<0.001). Subgroup analyses yielded similar results. In a subgroup analysis, carvedilol appeared to be superior to metoprolol for the prevention of POAF (RR 0.51, 95% CI 0.37 to 0.70, p<0.001). No evidence of heterogeneity was observed. Conclusions: In conclusion, carvedilol may effectively reduce the incidence of POAF in patients undergoing cardiac surgery. It appeared to be superior to metoprolol. A large-scale, well-designed randomized controlled trial is needed to conclusively answer the question regarding the utility of carvedilol in the prevention of POAF. © 2014 Wang et al.
Wang Z.,Shenyang Northern Hospital |
Ouyang J.,Fuzhou General Hospital of Nanjing Command |
Liang Y.,Shenyang Northern Hospital |
Jin Z.,Shenyang Northern Hospital |
And 5 more authors.
Circulation: Arrhythmia and Electrophysiology | Year: 2015
Background - Focal atrial tachycardias (ATs) surrounding the anterior atrial septum (AAS) have been successfully ablated from the right atrial septum (RAS), the aortic cusps, and the aortic mitral junction. However, the strategy for mapping and ablation of AAS-ATs has not been well defined. Methods and Results - Of 227 consecutive patients with AT, 47 (20.7%; mean age, 56.3±11.6 years) with AAS-ATs were studied; among them, initial ablation was successful at RAS in only 5 of 14 patients and at noncoronary cusp (NCC) in 28 of 33 patients. In 45 of the 47 patients, the 46 of 48 AAS-ATs were eliminated at RAS in 8 patients, NCC in 35 patients (earliest activation time at NCC was later than that at RAS by 5-10 ms in 6 patients), and aortic mitral junction in 3 patients (all with negative P wave in lead aVL and positive P wave in the inferior leads), including 1 patient whose 2 ATs were eliminated separately from the NCC and the aortic mitral junction. Conclusions - Most of the ATs surrounding the AAS can be eliminated from within the NCC, which is usually the preferential ablation site. Ablation at the RAS and aortic mitral junction should be considered when supported by P-wave morphologies on surface ECG and results of activation mapping and ablation. © 2015 American Heart Association, Inc.