Ya-Ling Han

General Hospital of Shenyang Military Region, Feng-t’ien, Liaoning, China

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Publications (105)124.83 Total impact

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    ABSTRACT: To date, transcatheter arterial embolization (TAE) has become a standard treatment to control intracavitary bleeding as an alternative to surgery. Due to excellent biocompatibility and no residual in vivo, biodegradable materials are preferred in TAE. However, gelfoam is the only commercially available biodegradable embolic material used to treat blunt trauma of solid abdominal viscera until now, and controversial on its stability and reliability never stopped in the past five decades. In this study, a new biodegradable macromolecule material (thrombin-loaded alginate-calcium microspheres, TACMs) was prepared using electrostatic droplet techniques and a special method was developed for hemostatic embolization. Thrombin was successfully loaded into microspheres with high encapsulation efficiency and drug loading capacity. A burst release of TACMs was observed at early stage and sustained release later on, with the activity of thrombin preserved well. The strength of TACMs mixed thrombus, which was used as embolic agent, increased in a dose-dependent manner after TACMs were added. In addition, the TACMs were verified to be of no cytotoxicity and systemic toxicity, and biodegradable in vivo. Finally, the results of preliminary applications revealed that the TACMs could serve as an effective and promising embolic material for blunt trauma and hemorrhage of solid abdominal viscera. Copyright © 2015. Published by Elsevier B.V.
    International Journal of Biological Macromolecules 01/2015; DOI:10.1016/j.ijbiomac.2014.12.043 · 3.10 Impact Factor
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    ABSTRACT: Low responsiveness to clopidogrel (LRC) is associated with increased risk of ischemic events. This study was aimed to explore the feasibility of tailored antiplatelet therapy according to the responsiveness to clopidogrel. A total of 305 clopidogrel naïve patients with acute coronary syndromes (ACS) undergoing coronary stenting were randomly assigned to receive standard (n = 151) or tailored (n = 154) antiplatelet therapy. The ADP-induced platelet aggregation tests by light transmission aggregometry were performed to identify LRC patients assigned to the tailored group. The standard antiplatelet regimen was dual antiplatelet therapy with aspirin and clopidogrel. The tailored antiplatelet therapy was standard regimen for non-LRC patients and an additional 6-month cilostazol treatment for LRC patients. The primary efficacy outcome was the composite of cardiovascular death, myocardial infarction or stroke at one year. LCR was present in 26.6% (41/154) of patients in the tailored group. The percentage platelet aggregation for LCR patients was significantly decreased at three days after adjunctive cilostazol treatment (77.5% ± 12.1% vs. 64.5% ± 12.1%, P < 0.001). At one year follow-up, a non-significant 37% relative risk reduction of primary events were observed in the tailored group as compared to the standard group (5.8% vs. 9.3%, P = 0.257). There were no differences in the rates of stent thrombosis and hemorrhagic events between the two groups. Tailored antiplatelet therapy for ACS patients after coronary stenting according to responsiveness to clopidogrel is feasible. However, its efficacy and safety need further confirmation by clinical trials with larger sample sizes.
    Journal of Geriatric Cardiology 01/2015; 12(1):23-29. DOI:10.11909/j.issn.1671-5411.2015.01.003 · 1.06 Impact Factor
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    ABSTRACT: MiR-495 is down-regulated in the plasma of CAD patients compared with controls•MiR-495 inhibits CCL2 expression by directly binding to its 3’ UTR of CCL2 gene•MiR-495 induces the proliferation and inhibits the apoptosis of HUVECs•CCL2 mediates the roles of miR-495 on HUVECs proliferation and apoptosis
    Thrombosis Research 11/2014; DOI:10.1016/j.thromres.2014.10.027 · 2.43 Impact Factor
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    ABSTRACT: Objectives The present study established criteria to differentiate simple from complex bifurcation lesions and compared 1-year outcomes stratified by lesion complexity after provisional stenting (PS) and 2-stent techniques using drug-eluting stents. Background Currently, no criterion can distinguish between simple and complex coronary bifurcation lesions. Comparisons of PS and 2-stent strategies stratified by lesion complexity have also not been reported previously. Methods Criteria of bifurcation complexity in 1,500 patients were externally tested in another 3,660 true bifurcation lesions after placement of drug-eluting stents. The primary endpoint was the occurrence of a major adverse cardiac event (MACE) at 12 months. The secondary endpoint was the rate of stent thrombosis (ST). Results Complex (n = 1,108) bifurcation lesions were associated with a higher 1-year rate of MACE (16.8%) compared with simple (n = 2,552) bifurcation lesions (8.9%) (p < 0.001). The in-hospital ST and 1-year target lesion revascularization rates after 2-stent techniques in the simple group (1.0% and 5.6%, respectively) were significantly different from those after PS (0.2% [p = 0.007] and 3.2% [p = 0.009], respectively); however, 1-year MACE rates were not significantly different between the 2 groups. For complex bifurcation lesions, 2-stent techniques had lower rates of 1-year cardiac death (2.8%) and in-hospital MACE (5.0%) compared with PS (5.3%, p = 0.047; 8.4%, p = 0.031). Conclusions Complex bifurcation lesions had higher rates of 1-year MACE and ST. The 2-stent and PS techniques were overall equivalent in 1-year MACE. However, 2-stent techniques for complex lesions elicited a lower rate of cardiac death and in-hospital MACE but higher rates of in-hospital ST and revascularization at 1 year for simple lesions.
    JACC Cardiovascular Interventions 10/2014; DOI:10.1016/j.jcin.2014.04.026 · 7.44 Impact Factor
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    ABSTRACT: ObjectiveTo evaluate the long-term efficacy of covered stent implantation in the treatment of elderly patients with coronary perforation while undergoing percutaneous coronary intervention (PCI).MethodsFrom June 2004 to June 2012, our center has followed ten elderly patients (age ≥ 60 years) who sustained coronary perforation during PCI. The major adverse cardiac events (MACE) were observed as well. The patients were advised to take 75 mg/day Clopidogrel for two years, and indefinite use of 100 mg/day enteric-coated aspirin.ResultsSix out of the 10 patients aged from 60 to 76 years old (mean 68.6 ± 5.2 years) were male, four were female. The average diameter of the implanted stents was 3.3 ± 0.3 mm, and the average length was 22.1 ± 3.7 mm. All the ruptures were successfully sealed without intra-procedural death. The follow-up duration ranged from 0.6 to 67 months (mean 31.7 ± 24.5 months). One patient died of multiple organ failure due to lung infection in 19 days after PCI; one died of cardiac sudden death in 13 months after PCI; one had angina pectoris in 53 months after PCI; one underwent multi-slice CT examination in six months after PCI, and no in-stent restenosis was found. The other four patients received angiography follow-up, and the results showed that three patients had no intra-stent restenosis, while one had left anterior descending (LAD) restenosis in the covered stent in 67 months after PCI. The in-hospital mortality was 10% (1/10). The MACE rate in 12 months after PCI was 10% (1/10). During the entire followed-up period, the restenosis rate in target vessels was 20% (1/5), mortality was 20% (2/10), and the MACE rate was 40% (4/10).ConclusionTreatment of coronary perforation by using covered stents can achieve favorable long-term results; a two-year dual antiplatelet therapy (DAPT) after PCI can effectively prevent intra-stent thrombosis.
    Heart (British Cardiac Society) 09/2014; 11(3):218-21. DOI:10.11909/j.issn.1671-5411.2014.03.009 · 6.02 Impact Factor
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    ABSTRACT: In cardiomyocytes subjected to stress, autophagy activation is a critical survival mechanism that preserves cellular energy status while degrading damaged proteins and organelles. However, little is known about the mechanisms that govern this autophagic response. Cellular repressor of E1A genes (CREG1) is an evolutionarily conserved lysosomal protein, and an important new factor in regulating tissues homeostasis that has been shown to antagonize injury of tissues or cells. In the present study, we aimed to investigate the regulatory role of CREG1 in cardiac autophagy, and to clarify autophagy activation mechanisms. First, we generated a CREG1 haploinsufficiency (Creg1(+/-)) mouse model, and identified that CREG1 deficiency aggravates myocardial fibrosis in response to aging or angiotensin II (Ang II). Conversely, exogenous infusion of recombinant CREG1 protein complete reversed cardiac damage. CERG1 deficiency in Creg1(+/-) mouse heart showed a market accumulation of autophagosome that acquired LC3II and beclin-1, and a decrease in autophagic flux clearance as indicated by upregulating the level of p62. Inversely, restoration of CREG1 activates cardiac autophagy, Furthermore, chloroquine, an inhibitor of lysosomal acidification, was used to confirm that CREG1 protected the heart tissue against Ang II-induced fibrosis by activating autophagy. Using adenoviral infection of primary cardiomyocytes, overexpression of CREG1 with concurrent resveratrol treatment significantly increased autophagy, while silencing CREG1 blocked the resveratrol-induced autophagy. These results suggest that CREG1-induced autophagy is required to maintain heart function in the face of stress-induced myocardiac damage. Both in vitro and in vivo studies identified that CREG1 deficiency influenced the maturation of lysosomes and reduced the espression of Rab7, which might be involved in CREG1-induced cardiomyocyte autophagy. These findings suggest that autophagy activation via CREG1 may be a viable therapeutic strategy autophagy for improving cardiac performance under pathologic conditions. This article is part of a Special Issue entitled: autophagy and protein quality control in cardiometabolic diseases. Copyright © 2014 Elsevier B.V. All rights reserved.
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 06/2014; 1852(2). DOI:10.1016/j.bbadis.2014.05.027 · 5.09 Impact Factor
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    ABSTRACT: Aims: The SYNTAX score has been proposed as a valuable tool to characterise coronary anatomy prospectively based on its complexity. This study evaluated the prognostic value on adverse outcomes of the residual SYNTAX score (rSS) in patients with complex lesions treated with an everolimus-eluting stent (EES). Methods and results: One thousand eight hundred and fifty-one patients with small vessel (reference diameter <2.75 mm), long lesion (length >25 mm), or multivessel (>2 target vessels) disease who underwent percutaneous coronary intervention (PCI) with EES in the prospective SEEDS (A Registry To Evaluate Safety And Effectiveness Of Everolimus Drug Eluting Stent For Coronary Revascularization) trial were categorised into low (<6), mid (>6-<12) and high (>12) baseline SYNTAX score (bSS) groups, and into low (=0), mid (>0-<5) and high (>5) rSS groups. Mean bSS and rSS were 10.87±7.26 and 2.18±3.97, respectively; 64% of patients had complete revascularisation (rSS=0). At 12 months the primary outcome of ischaemia-driven target vessel failure (TVF, composite of cardiac death, target vessel myocardial infarction and ischaemia-driven target vessel revascularisation) was significantly higher in the high bSS and rSS groups than in the respective lower groups (p<0.01 for both). In multivariable analysis, rSS was an independent predictor of TVF (hazard ratio: 1.403, 95% confidence interval: 1.081 to 1.820, p=0.01). Conclusions: Twelve-month TVF was significantly higher in the highest rSS group; rSS with a cut-off of 5 might therefore allow the risk stratification of patients with complex lesions treated with a second-generation drug-eluting stent (ClinicalTrials.gov identifier: NCT 01157455).
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 02/2014; 10(1). DOI:10.4244/EIJV10I1A12 · 3.17 Impact Factor
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    ABSTRACT: The present study aimed to establish a risk score using a simple calculation with an enhanced predictive value for major adverse cardiac events (MACE) in patients with unprotected left main coronary artery (UPLMCA) disease after the implantation of a drug-eluting stent (DES). The anatomic-, clinical-, and procedure-based NERS (New Risk Stratification) score was superior to the SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) score in predicting MACE after stenting UPLMCA. The complexity of the calculation was its major limitation. The NERS score II was derived from our previous 2 studies and externally compared with the NERS and SYNTAX scores in 1,463 patients with UPLMCA disease who underwent implantation of a DES in a prospective, multicenter registry trial. The primary endpoint was MACE at 1 year after the index procedure, including myocardial infarction, cardiac death, and target vessel revascularization. The NERS score II system consisted of 16 (7 clinical and 9 angiographic) variables. A NERS score II ≥19 demonstrated enhanced MACE sensitivity and specificity of 84.0% and 76.0% (MACE as the state variable), respectively, which were similar to the NERS score but significantly higher compared with the SYNTAX score. A NERS score II ≥19 was the only independent predictor of cumulative MACE (hazard ratio: 3.27; 95% confidence interval [CI]: 1.86 to 5.23; p ≤ 0.001) and stent thrombosis (odds ratio: 22.15; 95% CI: 12.47 to 57.92; p ≤ 0.001) at follow-up. The NERS score II, similar to the conventional NERS score, is more predictive of MACE than the SYNTAX score in UPLMCA patients after implantation of a DES.
    JACC. Cardiovascular Interventions 11/2013; 6(12). DOI:10.1016/j.jcin.2013.08.006 · 7.40 Impact Factor
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    ABSTRACT: The importance of matrix metalloproteinase 8 (MMP8) expression during the progression of thoracic aortic dissection (TAD) has been recently emphasized. Genetic variations that affect proteinase expression or activity might contribute to the pathogenesis of TAD. In this study, we investigated whether the MMP8 C-799T genotype is associated with TAD. The frequency distributions of the MMP8 C-799T polymorphism were determined by direct sequencing. Associations between the polymorphism and disease progression in TAD were investigated. The level of plasma and tissue MMP8 was measured by enzyme-linked immunosorbent assay and western blotting. The MMP8 C-799T polymorphism was significantly associated with susceptibility to disease progression in TAD patients (n = 152) than in controls (n = 147) (P = 0.004, OR = 0.62, 95 % CI 0.45-0.86). The TT homozygotes had a significantly higher risk of TAD compared to C allele carriers in a logistic regression model, after adjustment for the conventional risk factors for TAD. The plasma MMP8 concentration was significantly higher in TAD patients compared to control patients (P < 0.05). TT genotypes had increased MMP8 levels compared to CC and CT genotype carriers in both TAD and control subjects (P < 0.05). The C-799T polymorphism in the MMP8 promoter is part of the genetic variation underlying the susceptibility of individuals to the progression of TAD.
    Molecular Biology Reports 09/2013; 40(10). DOI:10.1007/s11033-013-2704-2 · 1.96 Impact Factor
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    ABSTRACT: To obtain a pure population of smooth muscle cells (SMC) derived from mouse embryonic stem cells (ESC) and further assess their functions. A vector, expressing both puromycin resistance gene (puro(r) ) and enhanced green fluorescent protein (EGFP) gene driven by smooth muscle 22α (SM22α) promoter, named pSM22α-puro(r)-IRES2-EGFP was constructed and used to transfect ESC. Transgenic ESC (Tg-ESC) clones were selected by G418 and identified by PCR amplification of puro(r) gene. The characteristics of Tg-ESC were detected by alkaline phosphatase (ALP) staining, SSEA-1 immunofluorescence and teratoma formation test in vivo. After induction of SMC differentiation by all-trans retinoic acid, differentiated Tg-ESC were treated with 10 µg/mL puromycin for three days to obtain purified SMC (P-SMC). Percentage of EGFP(+) cells in P-SMC was assessed by flow cytometer. Expressions of smooth muscle specific markers were detected by immunostaining and Western blotting. Proliferation, migration and contractility of P-SMC were analyzed by growth curve, trans-well migration assay, and carbachol treatment, respectively. Finally, both P-SMC and unpurified SMC (unP-SMC) were injected into syngeneic mouse to see teratoma development. Tg-ESC clone was successfully established and confirmed by PCR detection of puro(r) gene in its genomic DNA. The Tg-ESC was positive for ALP staining, SSEA-1 staining and formed teratoma containing tissues derived from three germ layers. After retinoic acid induction, large amount of EGFP positive cells outgrew from differentiated Tg-ESC. Three days of puromycin treatment produced a population of P-SMC with an EGFP(+) percentage as high as 98.2% in contrast to 29.47% of unP-SMC. Compared with primary mouse vascular smooth muscle cells (VSMC), P-SMC displayed positive, but lowered expression of SMC-specific markers including SM α-actin and myosin heavy chain (SM-MHC) detected either, by immunostaining, or immunoblotting, accelerated proliferation, improved migration (99.33 ± 2.04 vs. 44.00 ± 2.08 migrated cells/field, P < 0.05), and decreased contractility in response to carbachol (7.75 ± 1.19 % vs. 16.50 ± 3.76 % in cell area reduction, P < 0.05). In vivo injection of unP-SMC developed apparent teratoma while P-SMC did not. We obtained a pure population of ESC derived SMC with less mature (differentiated) phenotypes, which will be of great use in research of vascular diseases and in bio-engineered vascular grafts for regenerative medicine.
    Journal of Geriatric Cardiology 09/2013; 10(3):272-80. DOI:10.3969/j.issn.1671-5411.2013.03.003 · 1.06 Impact Factor
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    ABSTRACT: 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.
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 07/2013; 9(3):316-27. DOI:10.4244/EIJV9I3A53 · 3.17 Impact Factor
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    ABSTRACT: Aims: The study sought to evaluate the safety and efficacy of FIREHAWK, a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent (SES) for treating patients with single de novo coronary lesions compared with the durable polymer everolimus-eluting stent (EES) XIENCE V. Methods and results: A total of 458 patients with single de novo native coronary lesions ≤24 mm in length and a coronary artery ≥2.25 to ≤4.0 mm in diameter were enrolled in the TARGET I study, a prospective, randomised, non-inferiority trial. The primary endpoint was in-stent late lumen loss (LLL) at nine-month follow-up. The secondary endpoint, target lesion failure (TLF), was defined as the composite of cardiac death, target vessel myocardial infarction (TVMI), or ischaemia-driven target lesion revascularisation (iTLR). Patients were centrally randomised to treatment with either biodegradable polymer SES (n=227) or durable polymer EES (n=231). The nine-month in-stent LLL of the biodegradable polymer SES was comparable to the EES group (0.13±0.24 mm vs. 0.13±0.18 mm, p=0.94; difference and 95% confidence interval 0.00 [-0.04, 0.04] mm; p for non-inferiority <0.0001). Cardiac death (0.4% vs. 0.0%), TVMI (1.3% vs. 1.7%), iTLR (0.4% vs. 0.4%) and TLF (2.2% vs. 2.2%) were similar between the biodegradable polymer SES and durable polymer EES groups at 12-month follow-up (all p>0.05). No definite/probable stent thrombosis was observed in both of these groups. Conclusions: In the multicentre TARGET I trial, the novel abluminal groove-filled biodegradable polymer SES FIREHAWK was non-inferior to the durable polymer EES XIENCE V with respect to the primary endpoint of in-stent LLL at nine months for treating patients with single de novo coronary lesions. The incidences of clinical endpoints were low in both of the stents at 12-month follow-up. (ClinicalTrials.gov identifier: NCT01196819).
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 05/2013; 9(1):75-83. DOI:10.4244/EIJV9I1A12 · 3.17 Impact Factor
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    ABSTRACT: OBJECTIVES: To elucidate the efficacy and safety of pharmacoinvasive therapy by using prourokinase (prouk) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Patients with STEMI often have long PCI related delays due to various reasons, which are associated with poor outcomes. METHODS: A randomized study which enrolled patients from 4 centers in China was conducted. Patients were randomly assigned to accept routine primary PCI or prouk-PCI. The primary end points were the angiographic parameters, including TIMI flow grade, TIMI frame count and myocardial blush grade. Secondary endpoints were incidence of major adverse cardiac events (MACE, defined as death from all causes, reinfarction, revascularization, or rehospitalization due to new or worsening congestive heart failure) at 30 days and one year. RESULTS: 197 eligible patients were enrolled, of whom 100 were randomized to the prouk-PCI group. Significantly more patients in the prouk-PCI group than in the PCI group had an opened infarct related artery on arrival in the catheterization laboratory (48% vs. 21%, P=0.0002) and better TIMI frame count after PCI (33±6 vs. 40±10, P<0.001). At one-year follow-up, there was a trend that patients in the prouk-PCI group had less chances to have MACE (7.0% vs. 12.6%, P=0.235) or be readmitted to hospital due to new or worsening congestive heart failure (1.0% vs. 4.1%, P=0.209). CONCLUSION: A strategy of emergent PCI preceded by fibrinolysis with prouk results in a better myocardial perfusion in infarct related artery compared with primary PCI alone in patients with STEMI and long PCI related delay. © 2012 Blackwell Publishing Ltd.
    Cardiovascular Therapeutics 05/2013; 31(5). DOI:10.1111/1755-5922.12020 · 2.85 Impact Factor
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    ABSTRACT: Aims: To assess the immediate and long-term outcomes of transcatheter closure of ventricular septal defect (VSD) in combination with percutaneous coronary intervention (PCI) in patients with VSD complicating acute myocardial infarction (AMI). Methods and results: Data were prospectively collected from 35 AMI patients who underwent attempted transcatheter VSD closure and PCI therapy in five high-volume heart centres. All the patients who survived the procedures were followed up by chest x-ray, electrocardiogram and echocardiography. Thirteen patients underwent urgent VSD closure in the acute phase (within two weeks from VSD) while the others underwent elective closure at a median of 23 days from VSD occurrence. The percentage of VSD closure device success was 92.3% (36/39) and procedure success was 91.4% (32/35). The incidence of in-hospital mortality was 14.3% (5/35). At a median of 53 months follow-up, only two patients died at 38 and 41 months, respectively, and other patients' cardiac function tested by echocardiography improved significantly compared to that evaluated before discharge. Conclusion: The combination of transcatheter VSD closure and PCI for treating VSD complicating AMI is safe and feasible and is a promising alternative to surgery in patients with anatomically suitable VSD and coronary lesion.
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 03/2013; 8(11):1270-6. DOI:10.4244/EIJV8I11A195 · 3.17 Impact Factor
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    ABSTRACT: Phenotypic modulation of vascular smooth muscle cells (VSMCs) plays a critical role in the pathogenesis of a variety of proliferative vascular diseases. Cellular repressor of E1A-stimulated genes (CREG) has been shown to play an important role in phenotypic modulation of VSMCs. However, the mechanism regulating CREG upstream signaling remains unclear. MicroRNAs (miRNAs) have recently been found to play a critical role in cell differentiation via target-gene regulation. This study aimed to identify a miRNA that binds directly to CREG, and may thus be involved in CREG-mediated VSMC phenotypic modulation. Computational analysis indicated that miR-31 bound to the CREG mRNA 3' untranslated region (3'-UTR). miR-31 was upregulated in quiescent differentiated VSMCs and downregulated in proliferative cells stimulated by platelet-derived growth factor and serum starvation, demonstrating a negative relationship with the VSMC differentiation marker genes, smooth muscle α-actin, calponin and CREG. Using gain-of-function and loss-of-function approaches, CREG and VSMC differentiation marker gene expression levels were shown to be suppressed by a miR-31mimic, but increased by a miR-31 inhibitor at both protein and mRNA levels. Notably, miR-31 overexpression or inhibition affected luciferase expression driven by the CREG 3'-UTR containing the miR-31 binding site. Furthermore, miR-31-mediated VSMC phenotypic modulation was inhibited in CREG-knockdown human VSMCs. We also determined miR-31 levels in the serum of patients coronary artery disease (CAD) with or without in stent restenosis and in healthy controls. miR-31 levels were higher in the serum of CAD patients with restenosis compared to CAD patients without restenosis and healthy controls. In summary, these data demonstrate that miR-31 not only directly binds to its target gene CREG and modulates VSMC phenotype through this interaction, but also can be an important biomarker in diseases involving VSMC phenotypic modulation. These novel findings may have extensive implications for the diagnosis and therapy of a variety of proliferative vascular diseases.
    Experimental Cell Research 03/2013; DOI:10.1016/j.yexcr.2013.03.010 · 3.37 Impact Factor
  • Ya-Ling Han
    Chinese medical journal 03/2013; 126(6):1005-1007. · 1.02 Impact Factor
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    ABSTRACT: BACKGROUND: The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients. METHODS: In 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months. RESULTS: Genotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 (group 1), 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 (group 2), 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 (group 3), and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 (group 4). Group 4 had the lowest ADP-inhibition (49.74 ± 32.61) and the highest prevalence of clopidogrel low response (29.7%) of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 (8.5%) than in the other three groups; the rate of composite primary endpoints in group 2 (2.9%) and group 3 (3.7%) were not significantly different than that of group 1 (1.5%). CONCLUSION: Coexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.
    Chinese medical journal 03/2013; 126(6):1069-1075. · 1.02 Impact Factor
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    ABSTRACT: BACKGROUND: Previous studies indicated that long coronary lesions are one of the key predictors of drug-eluting stent (DES) failure. The purpose of this study was to evaluate the efficacy and the safety of the long length FIREHAWK(®) stent in long coronary artery disease. METHODS: The long cohort of TARGET I was a prospective, multicenter, single arm trial. It was planned to enroll 50 patients undergoing percutaneous coronary intervention (PCI) for the treatment of de novo long lesions in a native coronary artery. The major inclusion criteria of the trial was that patients were intended to undergo the treatment of a long target lesion(s) with diameter stenosis ≥ 70% and reference vessel diameter 2.5 mm to 4.0 mm by visual estimate, that needed to be covered by at least one 33 mm or 38 mm stent or multiple long stents overlapped. The angiographic follow-up was planned at 9-month and the clinical follow-up will be up to 5 years. The primary end point was in-stent late lumen loss at 9-month. RESULTS: Fifty patients (mean age (57.6 ± 10.2) years) with 59 de novo long lesions (reference vessel diameter (2.85 ± 0.44) mm, lesion length (35.2 ± 9.4) mm, and stent length (41.8 ± 11.3) mm) were enrolled. The angiographic follow-up rate was 92% at 9-month. The in-stent late loss was (0.16 ± 0.16) mm. Proximal edge, distal edge and in-segment late loss (mm) were 0.21 ± 0.35, 0.03 ± 0.33, and 0.07 ± 0.26, respectively. No in-segment binary restenosis was observed. At 1-year no death, Q wave myocardial infarction (MI), or stent thrombosis occurred. Non-Q-wave MI occurred in two patients (4%) due to procedural complications. CONCLUSIONS: Treatment of long coronary lesions with the FIREHAWK(®) stent is able to produce similar results as observed in the FIREHAWK(®) FIM clinical trial. Based on this result, we are confident in the treatment prospect of the FIREHAWK(®) for long coronary lesions.
    Chinese medical journal 03/2013; 126(6):1026-1032. · 1.02 Impact Factor
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    ABSTRACT: BACKGROUND: The gender difference on long-term outcome in unselected patients after percutaneous coronary intervention (PCI) has not yet been fully investigated. This study aimed to evaluate the gender difference on five-year outcomes following EXCEL biodegradable polymer-coated sirolimus-eluting stenting in patients with coronary disease. METHODS: A total of 2077 "all comers", consisting of 1528 (73.6%) men and 549 (26.4%) women, who were exclusively treated with EXCEL coronary stents were enrolled in the prospective CREATE study at 59 centers from four countries. After propensity score matching, the baseline characteristics of the two groups were well matched. Recommended antiplatelet regimen was clopidogrel and aspirin for six months followed by chronic aspirin therapy. The primary outcome that was the rate of major adverse cardiac events (MACE), defined as a composite of cardiac mortality, non-fatal myocardial infarction (MI) and target lesion revascularization (TLR), and stent thrombosis (ST) at five years were compared between the two gender groups. RESULTS: In the two groups, women had higher proportions of clinical risk factors, such as being elderly, diabetes mellitus, hypertension and hyperlipidemia, compared to men. Besides, the mean target vessel number per patient was higher and the mean reference vessel diameter smaller for women. Men had higher risks of cardiac death (3.7% vs. 1.6%, P = 0.021) and MACE (8.4% vs. 4.7%, P = 0.004) at five years compared with women. However, the cumulative hazards of non-fatal MI and TLR were similar between men and women. The incidence of Academic Research Consortium (ARC) definite or probable stent thrombosis was similar between the two groups (1.3% vs. 1.0%, P = 0.639). Prolonged clopidogrel therapy (>6 months) did not reduce the cumulative hazards of ST from six months to five years in both men (χ(2) = 0.098, log rank P = 0.754) and women (χ(2) = 2.043, log rank P = 0.153) patients. CONCLUSIONS: Women had a lower MACE and cardiac death rate than men after biodegradable polymer-coated sirolimus-eluting stenting in long term follow-up. Effects of prolonged dual antiplatelet therapy (DAPT) in preventing stent thrombosis was similar with six-month DAPT after EXCEL stent implantation in both men and women groups.
    Chinese medical journal 03/2013; 126(6):1039-1045. · 1.02 Impact Factor
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    ABSTRACT: OBJECTIVES: The study aimed to investigate the difference in major adverse cardiac event (MACE) at 1-year after double kissing (DK) crush versus culotte stenting for unprotected left main coronary artery (UPLMCA) distal bifurcation lesions. BACKGROUND: DK crush and culotte stenting were reported to be effective for treatment of coronary bifurcation lesions. However, their comparative performance in UPLMCA bifurcation lesions is not known. METHODS: A total of 419 patients with UPLMCA bifurcation lesions were randomly assigned to DK (n = 210) or culotte (n = 209) treatment. The primary endpoint was the occurrence of a MACE at 1 year, including cardiac death, myocardial infarction, and target vessel revascularization (TVR). In-stent restenosis (ISR) at 8 months was secondary endpoint, and stent thrombosis (ST) served as a safety endpoint. Patients were stratified by SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) and NERS (New Risk Stratification) scores. RESULTS: Patients in the culotte group had significant higher 1-year MACE rate (16.3%), mainly driven by increased TVR (11.0%), compared with the DK group (6.2% and 4.3%, respectively; all p < 0.05). ISR rate in side branch was 12.6% in the culotte group and 6.8% in the DK group (p = 0.037). Definite ST rate was 1.0% in the culotte group and 0% in the DK group (p = 0.248). Among patients with bifurcation angle ≥70°, NERS score ≥20, and SYNTAX score ≥23, the 1-year MACE rate in the DK group (3.8%, 9.2%, and 7.1%, respectively) was significantly different to those in the culotte group(16.5%, 20.4%, and 18.9%, respectively; all p < 0.05). CONCLUSIONS: Culotte stenting for UPLMCA bifurcation lesions was associated with significantly increased MACEs, mainly due to the increased TVR. (Double Kissing (DK) Crush Versus Culotte Stenting for the Treatment of Unprotected Distal Left Main Bifurcation Lesions: DKCRUSH-III, a Multicenter Randomized Study Comparing Double-Stent Techniques; ChiCTR-TRC-00000151).
    Journal of the American College of Cardiology 02/2013; 61(14). DOI:10.1016/j.jacc.2013.01.023 · 15.34 Impact Factor

Publication Stats

200 Citations
124.83 Total Impact Points


  • 2003–2015
    • General Hospital of Shenyang Military Region
      Feng-t’ien, Liaoning, China
  • 2013–2014
    • Northern Inyo Hospital
      Bishop, California, United States
  • 2003–2012
    • 307 Hospital of the Chinese People's Liberation Army
      Peping, Beijing, China
  • 2008–2009
    • Fourth Military Medical University
      • Department of Cardiology
      Xi’an, Liaoning, China
  • 2005–2009
    • Chinese PLA General Hospital (301 Hospital)
      Peping, Beijing, China