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, Volume 14 Issue 8 Previous Issue    Next Issue
Perspectives
Outcomes research: science and action
Henry H. Ting, Mei-xiang Xiang, Jian-an Wang
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(8): 659-663.   https://doi.org/10.1631/jzus.BQICC705
Abstract( 1905 )     PDF(0KB)( 943 )
Outcomes research, which investigates the outcomes of health care practices, is intended to provide scientific evidence for clinical decision making and health care. This paper elucidates the goal and domains of outcomes research. Also it shows the potential and promise of outcomes research to provide a methodology to uncover what to do and how to do it, and enable the health care profession to achieve the right care, for the right patient, at the right time, the first time, every time, nothing more, and nothing less.
Interleukin-17 and acute coronary syndrome
Sheng-an Su, Hong Ma, Li Shen, Mei-xiang Xiang, Jian-an Wang
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(8): 664-669.   https://doi.org/10.1631/jzus.BQICC701
Abstract( 1306 )     PDF(0KB)( 846 )
Inflammation plays an important role in atherosclerosis, which is also crucial for acute coronary syndrome (ACS). Recent studies have revealed that interleukin (IL)-17, which was regarded as a pro-inflammatory cytokine, has a dual function in the progress of ACS. In this review, we sum up both experimental and clinical studies on the relevance of IL-17 to atherosclerosis and its complications, and summarize the research progress on the effect of IL-17 on the atherosclerotic plaque stability and ACS onset. Although the studies are controversial and the mechanism remains unclear, we highlight the knowledge of the role of IL-17 in ACS and elucidate its potential mechanism.
Update of transcatheter valve treatment
Xian-bao Liu, Jian-an Wang
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(8): 670-675.   https://doi.org/10.1631/jzus.BQICC702
Abstract( 1081 )     PDF(0KB)( 786 )
Transcatheter valve implantation or repair has been a very promising approach for the treatment of valvular heart diseases since transcatheter aortic valve implantation (TAVI) was successfully performed in 2002. Great achievements have been made in this field (especially TAVI and transcatheter mitral valve repair—MitraClip system) in recent years. Evidence from clinical trials or registry studies has proved that transcatheter valve treatment for valvular heart diseases is safe and effective in surgical high-risk or inoperable patients. As the evidence accumulates, transcatheter valve treatment might be an alterative surgery for younger patients with surgically low or intermediate risk valvular heart diseases in the near future. In this paper, the updates on transcatheter valve treatment are reviewed.
Reviews
Advances in monoclonal antibody application in myocarditis
Li-na Han, Shuang He, Yu-tang Wang, Li-ming Yang, Si-yu Liu, Ting Zhang
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(8): 676-687.   https://doi.org/10.1631/jzus.BQICC711
Abstract( 1632 )     PDF(0KB)( 787 )
Monoclonal antibodies have become a part of daily preparation technologies in many laboratories. Attempts have been made to apply monoclonal antibodies to open a new train of thought for clinical treatments of autoimmune diseases, inflammatory diseases, cancer, and other immune-associated diseases. This paper is a prospective review to anticipate that monoclonal antibody application in the treatment of myocarditis, an inflammatory disease of the heart, could be a novel approach in the future. In order to better understand the current state of the art in monoclonal antibody techniques and advance applications in myocarditis, we, through a significant amount of literature research both domestic and abroad, developed a systematic elaboration of monoclonal antibodies, pathogenesis of myocarditis, and application of monoclonal antibodies in myocarditis. This paper presents review of the literature of some therapeutic aspects of monoclonal antibodies in myocarditis and dilated cardiomyopathy to demonstrate the advance of monoclonal antibody application in myocarditis and a strong anticipation that monoclonal antibody application may supply an effective therapeutic approach to relieve the severity of myocarditis in the future. Under conventional therapy, myocarditis is typically associated with congestive heart failure as a progressive outcome, indicating the need for alternative therapeutic strategies to improve long-term results. Reviewing some therapeutic aspects of monoclonal antibodies in myocarditis, we recently found that monoclonal antibodies with high purity and strong specificity can accurately act on target and achieve definite progress in the treatment of viral myocarditis in rat model and may meet the need above. However, several issues remain. The technology on how to make a higher homologous and weak immunogenic humanized or human source antibody and the treatment mechanism of monoclonal antibodies may provide solutions for these open issues. If we are to further stimulate progress in the area of clinical decision support, we must continue to develop and refine our understanding and use of monoclonal antibodies in myocarditis.
Metabolic remodeling in chronic heart failure
Jing Wang, Tao Guo
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(8): 688-695.   https://doi.org/10.1631/jzus.B1300137
Abstract( 2271 )     PDF(0KB)( 1160 )
Although the management of chronic heart failure (CHF) has made enormous progress over the past decades, CHF is still a tremendous medical and societal burden. Metabolic remodeling might play a crucial role in the pathophysiology of CHF. The characteristics and mechanisms of metabolic remodeling remained unclear, and the main hypothesis might include the changes in the availability of metabolic substrate and the decline of metabolic capability. In the early phases of the disease, metabolism shifts toward carbohydrate utilization from fatty acids (FAs) oxidation. Along with the progress of the disease, the increasing level of the hyperadrenergic state and insulin resistance cause the changes that shift back to a greater FA uptake and oxidation. In addition, a growing body of experimental and clinical evidence suggests that the improvement in the metabolic capability is likely to be more significant than the selection of the substrate.
Articles
Effects of rosuvastatin on the production and activation of matrix metalloproteinase-2 and migration of cultured rat vascular smooth muscle cells induced by homocysteine
Ya-fei Shi, Ju-fang Chi, Wei-liang Tang, Fu-kang Xu, Long-bin Liu, Zheng Ji, Hai-tao Lv, Hang-yuan Guo
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(8): 696-704.   https://doi.org/10.1631/jzus.BQICC703
Abstract( 1275 )     PDF(0KB)( 689 )
Objective: To test the influence of homocysteine on the production and activation of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of matrix metalloproteinase-2 (TIMP-2) and on cell migration of cultured rat vascular smooth muscle cells (VSMCs). Also, to explore whether rosuvastatin can alter the abnormal secretion and activation of MMP-2 and TIMP-2 and migration of VSMCs induced by homocysteine. Methods: Rat VSMCs were incubated with different concentrations of homocysteine (50–5000 μmol/L). Western blotting and gelatin zymography were used to investigate the expressions and activities of MMP-2 and TIMP-2 in VSMCs in culture medium when induced with homocysteine for 24, 48, and 72 h. Transwell chambers were employed to test the migratory ability of VSMCs when incubated with homocysteine for 48 h. Different concentrations of rosuvastatin (10−9–10−5 mol/L) were added when VSMCs were induced with 1000 μmol/L homocysteine. The expressions and activities of MMP-2 and TIMP-2 were examined after incubating for 24, 48, and 72 h, and the migration of VSMCs was also examined after incubating for 48 h. Results: Homocysteine (50–1000 μmol/L) increased the production and activation of MMP-2 and expression of TIMP-2 in a dose-dependent manner. However, when incubated with 5000 μmol/L homocysteine, the expression of MMP-2 was up-regulated, but its activity was down-regulated. Increased homocysteine-induced production and activation of MMP-2 were reduced by rosuvastatin in a dose-dependent manner whereas secretion of TIMP-2 was not significantly altered by rosuvastatin. Homocysteine (50–5000 μmol/L) stimulated the migration of VSMCs in a dose-dependent manner, but this effect was eliminated by rosuvastatin. Conclusions: Homocysteine (50–1000 μmol/L) significantly increased the production and activation of MMP-2, the expression of TIMP-2, and the migration of VSMCs in a dose-dependent manner. Additional extracellular rosuvastatin can decrease the excessive expression and activation of MMP-2 and abnormal migration of VSMCs induced by homocysteine.
Clinical and angiographic features associated with coronary collateralization in stable angina patients with chronic total occlusion
Zhen Sun, Ying Shen, Lin Lu, Rui-yan Zhang, Li-jin Pu, Qi Zhang, Zheng-kun Yang, Jian Hu, Qiu-jing Chen, Wei-feng Shen
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(8): 705-712.   https://doi.org/10.1631/jzus.BQICC704
Abstract( 1586 )     PDF(0KB)( 839 )
Objective: Coronary collateral circulation is an alternative source of blood supply to myocardium in the presence of advanced coronary artery disease. We sought to determine which clinical and angiographic variables are associated with collateral development in patients with stable angina and chronic total coronary occlusion. Methods: Demographic variables, biochemical measurements, and angiographic findings were collected from 478 patients with stable angina and chronic total coronary occlusion. The presence and extent of collaterals supplying the distal aspect of a total coronary occlusion from the contra-lateral vessel were graded from 0 to 3 according to the Rentrop scoring system. Results: Low (Rentrop score of 0 or 1) and high (Rentrop score of 2 or 3) coronary collateralizations were detected in 186 and 292 patients, respectively. Despite similar age, cigarette smoking, and medical treatment, patients with low collateralization were female in a higher proportion and less hypertensive, and had higher rates of type 2 diabetes and dyslipidemia than those with high collateralization (for all comparisons, P<0.05). In addition, patients with low collateralization exhibited more single-vessel disease, less right coronary artery occlusion, more impaired renal function, and higher serum levels of high-sensitivity C-reactive protein (hsCRP) compared with those with high collateralization. Multivariate analysis revealed that age of ≥65 years, female gender, diabetes, no history of hypertension, dyslipidemia, moderate to severe renal dysfunction, single-vessel disease, and elevated hsCRP levels were independently associated with low coronary collateralization. Conclusions: Coronary collateralization was reduced in almost 40% of stable angina patients with chronic total occlusion, which was related to clinical and angiographic factors. The impact of coronary collateralization on outcomes after revascularization needs further investigation.
A correlation between acute kidney injury and myonecrosis after scheduled percutaneous coronary intervention
Min Zhang, Hao-yu Meng, Ying-ming Zhao, Zhi-wen Tao, Xiao-xuan Gong, Ze-mu Wang, Bo Chen, Zheng-xian Tao, Chun-jian Li, Tie-bing Zhu, Lian-sheng Wang, Zhi-jian Yang
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(8): 713-720.   https://doi.org/10.1631/jzus.BQICC706
Abstract( 1301 )     PDF(0KB)( 672 )
Slight elevations in cardiac troponin I and T are frequently observed after percutaneous coronary intervention (PCI). Contrast-induced acute kidney injury (CI-AKI) is a complex syndrome induced by exposure to intravascular contrast media (CM). Currently, the relationships between the CM, pre-existing kidney insufficiency, CI-AKI, and myonecrosis after elective PCI are unclear. To investigate the relationship between CI-AKI and post-procedural myonecrosis (PMN) after PCI, we analyzed 327 non-ST-segment elevation acute coronary syndrome subjects undertaking elective PCI. The levels of cardiac troponins (cTns), cTnI and cTnT, at baseline and on at least one occasion 18–24 h after PCI were measured. We also recorded serum levels of creatinine (SCr) and the urine albumin:creatinine ratio (ACR) before coronary angiography, and 24–48 h and 48–72 h after contrast administration. A post-procedure increase in cTns was detected in 16.21% (53/327) of subjects with cTns levels >99th to 5&time;99th percentile upper reference limit (URL). Twenty-seven patients (8.26%) developed CI-AKI. CI-AKI occurred more often in subjects with PMN than in those without PMN (20.8% versus 5.8%, respectively, P=0.001). Multiple logistic regression analysis revealed that pre-existing microalbuminuria (MA) was an important independent predictor of PMN (OR: 3.31; 95% CI: 1.26–8.65, P=0.01). However, there was no correlation between the incidence of CI-AKI and PMN (OR: 2.38; 95% CI: 0.88–6.46, P=0.09). We conclude that pre-existing MA was not only an important independent predictor of CI-AKI but also of PMN.
Influence of serum adiponectin level and SNP +45 polymorphism of adiponectin gene on myocardial fibrosis
Cheng-jun Yan, Su-mei Li, Qiang Xiao, Yan Liu, Jian Hou, Ai-fang Chen, Li-ping Xia, Xiu-chang Li
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(8): 721-728.   https://doi.org/10.1631/jzus.BQICC707
Abstract( 1081 )     PDF(0KB)( 729 )
Adiponectin plays an important role in the development of hypertension, atherosclerosis, and cardiomyocyte hypertrophy, but very little was known about the influence of serum adiponectin or the adiponectin gene polymorphism on myocardial fibrosis. Our study investigates the influence of the SNP +45 polymorphism of the adiponectin gene and serum levels of adiponectin on myocardial fibrosis in patients with essential hypertension. A case-control study was conducted on 165 hypertensive patients and 126 normotensive healthy controls. The genotypes of adiponectin gene polymorphisms were detected by the polymerase chain reaction (PCR) method. Serum concentrations of procollagen were measured by a double antibody sandwich enzyme-linked immunosorbent assay (ELISA) in all subjects. The integrated backscatter score (IBS) was measured in the left ventricular myocardium using echocardiography. The serum levels of adiponectin in hypertensive patients were significantly lower than those in the normal control group ((2.69±1.0) μg/ml vs. (4.21±2.89) μg/ml, respectively, P<0.001). The serum levels of type-I procollagen carboxyl end peptide (PICP) and type-III procollagen ammonia cardinal extremity peptide (PIIINP) in the hypertension group were significantly higher than those in the control group. In the hypertension group, serum levels of adiponectin were significantly and negatively related to the average acoustic intensity and corrected acoustic intensity of the myocardium (r=0.46 and 0.61, respectively, P<0.05 for both). The serum levels of PICP and PIIINP were significantly different among the three genotypes of SNP +45 (P<0.01). Logistic regression analyses showed that sex and genotype (GG+GT) were the major risk factors of myocardial fibrosis in hypertensive patients (OR=5.343 and 3.278, respectively, P<0.05). These data suggest that lower levels of adiponectin and SNP +45 polymorphism of the adiponectin gene are likely to play an important role in myocardial fibrosis in hypertensive patients.
Gorham-Stout syndrome in mainland China: a case series of 67 patients and review of the literature
Po Hu, Xiang-gui Yuan, Xin-yang Hu, Fa-rong Shen, Jian-an Wang
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(8): 729-735.   https://doi.org/10.1631/jzus.B1200308
Abstract( 1631 )     PDF(0KB)( 1175 )
Objective: Gorham-Stout syndrome (GSS) is a rare disorder of uncertain etiology and unpredictable prognosis. This study aims to present a comprehensive understanding of this rare entity. Methods: A literature search in PubMed and three Chinese databases was performed to screen histologically proven GSS cases among Chinese residents in the mainland. We analyzed the patients鈥?clinical characteristics, the value of different treatment modalities and their influence on the clinical outcome. Results: Sixty-seven cases were finally enrolled. There were 43 men (64.2%) and 24 women (35.8%). The mean age at diagnosis was 28 years (1.5鈥?1 years). The most common clinical symptoms included pain (n=40, 59.7%), functional impairment (n=13, 19.4%), and swelling (n=12, 17.9%). The radiographic presentation of 37 cases (55.2%) was disappearance of a portion of the bone. The others presented as radiolucent foci in the intramedullary or subcortical regions. A total of 42 cases provided data on therapy, these included surgery (n=27, 40.3%), radiation therapy (n=6, 9.0%), surgery combined with radiation therapy (n=2, 3.0%), and medicine therapy (n=7, 10.4%). For 30 of these 42 cases, follow-up data were available: 21 cases had the disorder locally controlled and 9 had a symptom progression. Fortunately, the disease is not fatal in the majority of cases. Conclusions: GSS has no specific symptoms and it should be taken into consideration when an unclear massive osteolysis occurs. The efficacies of different treatment modalities are still unpredictable and further research is required to assess the values of different treatments.
Risk of cardiac rupture after acute myocardial infarction is related to a risk of hemorrhage
Geng Qian, Hong-bin Liu, Jin-wen Wang, Chen Wu, Yun-dai Chen
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(8): 736-742.   https://doi.org/10.1631/jzus.B1200306
Abstract( 1408 )     PDF(0KB)( 967 )
Although cardiac rupture (CR) is a fatal mechanical complication of acute myocardial infarction (AMI), to date no predictive model for CR has been described. CR has common pathological characteristics with major bleeding. We aimed to investigate the relationship between the risk factors of major bleeding and CR. A total of 10202 consecutive AMI patients were recruited, and mechanical complications occurred in 72 patients. AMI patients without CR were chosen as control group. Clinical characteristics including bleeding-related factors were compared between the groups. The incidences of free wall rupture (FWR), ventricular septal rupture (VSR), and papillary muscle rupture (PMR) were 0.39%, 0.21%, and 0.09%, respectively, and the hospital mortalities were 92.5%, 45.5%, and 10.0%, respectively. Female proportion and average age were significantly higher in the groups of FWR and VSR than in the control group (P<0.01); higher white blood cell count and lower hemoglobin were found in all CR groups (P<0.01). Compared to the control group, patients with CR were more likely to receive an administration of thrombolysis [26.39% vs. 13.19%, P<0.05], and were less likely to be treated with primary percutaneous coronary intervention (PCI) [41.67% vs. 81.60%, P<0.05]. The major bleeding scores (integer scores) of FWR, VSR, and PMR were (17.70±7.24), (21.91±8.33), and (18.60±7.88), respectively, and were significantly higher than that of the control group (11.72±7.71) (P<0.05). A regression analysis identified age, increased heart rate, anemia, higher white blood cell count, and thrombolysis as independent risk factors of CR, most of which were major bleeding-related factors. The patients with CR have a significantly higher risk of hemorrhage compared to the group without CR. Risk of CR after AMI is related to the risk of hemorrhage.
Factors underlying the association of body mass index with serum ALT in Chinese hypertensive adults without known hepatic diseases
Yan Zhang, Xian-hui Qin, Jian-ping Li, Yi-min Cui, Ze-yuan Liu, Zhi-gang Zhao, Jun-bo Ge, De-ming Guan, Jian Hu, Yan-ni Wang, Fu-min Zhang, Xin Xu, Xi-ping Xu, Yong Huo
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(8): 743-748.   https://doi.org/10.1631/jzus.B1200330
Abstract( 1827 )     PDF(0KB)( 924 )
Objective: High body mass index (BMI) is considered as the most important risk factor for elevated serum alanine aminotransferase (ALT) concentration. This study examined an array of factors, including waist circumference (WC) and folate deficiency, which may mediate the association of BMI with serum ALT concentration in Chinese hypertensive adults without known hepatic diseases. Methods: A multicenter, cross-sectional study was carried out. A total of 378 patients with mild or moderate hypertension and without known hepatic diseases were recruited from five hospitals in Harbin, Shanghai, Beijing, Xi’an, and Nanjing. Results: Of the 360 hypertensive patients with complete data in our final analysis, 13.6% had high ALT concentrations (>40 IU/L). Factors including BMI, WC, triglyceride level, and folate concentration were associated with ALT concentration in univariate analysis. Consistently higher prevalence rates of elevated ALT were observed in subjects with lower folate concentrations (≥12 vs. <12 nmol/L, 9.9% vs. 17.8%, P=0.03), with higher BMI (≥28 vs. <28 kg/m2, 21.5% vs. 11.4%, P=0.02) or higher WC (≥90 vs. <90 cm, 18.5% vs. 10.0%, P=0.02). However, in multivariate analysis, the association between BMI and ALT concentration disappeared (P=0.802 in males and 0.369 in females), while WC in females (P<0.001) and folate concentration (P=0.036 in males and 0.044 in females) remained as significant predictors for ALT concentration. Conclusions: This multicenter study demonstrated that WC and low folate concentration were important factors underlying the association between BMI and ALT concentrations in Chinese hypertensive adults without known hepatic diseases.
Letters
Correlation between virus persistent infection and cardic function in patients with dilated cardiomyopathy
Qiang Liu, Xiao-jia Su, Yan Yu, Yong-lin Liu
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(8): 749-753.   https://doi.org/10.1631/jzus.BQICC708
Abstract( 1063 )     PDF(0KB)( 733 )
In our study, 50 patients with dilated cardiomyopathy (DCM) were selected to investigate the correlation between virus persistent infection and cardic function. We found that 44% of patients with DCM were coxsackie virus B-RNA (CVB-RNA) positive, significantly different from that (20%) of the normal control group (P<0.05). The expression levels of coxsackie adenovirus receptor (CAR) in patients with DCM were significantly higher than those in the normal control group (P<0.01). In CVB-RNA-positive patients, expression levels of CAR were significantly higher than those in CVB-RNA-negative patients (P<0.01). There was a positive correlation between CAR expression and brain natriuretic peptide (BNP) level in patients with DCM, but no significant correlations between the CAR expression level and left ventricular ejection fraction (LVEF) or left ventricular end diastolic diameter (LVEDd). These results showed that expression levels of CAR on the surface of white cells can be used as an indicator for detecting persistent virus infection. We found that expression levels of CAR and heart function in patients with DCM were highly correlated.
Factors associated with decision time for patients with ST-segment elevation acute myocardial infarction
Lu Qian, Kang-ting Ji, Jin-liang Nan, Qin Lu, Yong-jin Zhu, Lu-ping Wang, Lian-ming Liao, Ji-fei Tang
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(8): 754-758.   https://doi.org/10.1631/jzus.BQICC709
Abstract( 1129 )     PDF(0KB)( 765 )
Increased delay in visiting a hospital for patients with ST-segment elevation myocardial infarction (STEMI) is often associated with poor outcomes. The factors associated with the decision time were analyzed by comparing the characteristics of patients with delays longer or shorter than the median of 60 min. Pre-hospital delay tended to be longer for patients living in suburban areas compared to those in urban areas (P=0.015). Shorter decision time was more likely among older patients. Being married, medical insurance coverage, and the level of educational qualification did not affect decision time. More efforts should be paid to educate the patients with high risk in suburban areas in order to effectively reduce pre-hospital delays.
Application of CRT-D in a Marfan syndrome patient with chronic heart failure accompanied by ventricular tachycardia and ventricular fibrillation
Hai-ying Xu, Yi-zhou Xu, Feng Ling, Zhong Yu, Jun Yang, Xu Duan, Bei Wang, Jin-yu Huang
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2013, 14(8): 759-762.   https://doi.org/10.1631/jzus.BQICC710
Abstract( 1186 )     PDF(0KB)( 682 )
Marfan syndrome is a systemic connective tissue disease that could affect the cardiovascular system and eventually lead to heart enlargement and heart failure with high mortality, mainly due to progressive heart failure and/or sudden cardiac death caused by malignant arrhythmia. Here we report that a patient received a cardiac resynchronization therapy-defibrillator (CRT-D) with a pre-monitor function for heart failure and experienced obvious improvements in his cardiac function. Postoperative follow-up showed that the patient had reduced morbidity and hospitalization for heart failure, and also experienced improved quality of life.
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