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Adenovirus-mediated tissue inhibitor of metalloproteinase-3 gene transfection inhibits rabbit intervertebral disc degeneration in vivo

Xudong YU MM, Zengwu SHAO MD, Liming XIONG MD, Weiwei XU MM, Hezhong WANG MM, Huifa XU MM,

Frontiers of Medicine 2009, Volume 3, Issue 4,   Pages 415-420 doi: 10.1007/s11684-009-0072-z

Abstract: The aim of this study was to investigate the inhibitory effects of recombinant adenovirus vector carrying tissue inhibitor of metalloproteinase-3 (RAdTIMP-3) against degeneration of rabbit intervertebral disc. Thirty Japanese white rabbits of 4 months old were randomly divided into 5 groups. Mild or moderate rabbit lumbar disc degeneration model was constructed with the controllable axial loading device by imposing 98N pressure at the discs for 2 weeks. Various doses of virus were injected into the degenerated discs as follows: 20μL of normal saline in group 1; 20μL of RAd66 (an empty adenovirus vector, 1.0×10OPU/mL) in group 2; and 20, 10, and 5μL of RAdTIMP-3 (1.0×10OPU/mL) in groups 3, 4, and 5, respectively. Two weeks after the injection, the discs were collected for investigations, including assessment of degeneration degrees according to the Thompson’s grading system, reverse-transcription polymerase chain reaction (RT-PCR) assay for TIMP-3 gene, Safranin O-Fast green staining, and immunohistochemical staining for TIMP-3 and type II collagen. According to Thompson’s criteria, the degeneration of groups 3, 4, and 5, especially group 3, was alleviated as compared with groups 1 and 2. RT-PCR revealed that the expression of TIMP-3 in groups 3, 4, and 5, especially in group 3, was significantly enhanced as compared with group 1 (<0.01). Both Safranin O-Fast green staining and type II collagen staining demonstrated better reserved integrity of disc matrix in groups 3, 4, and 5 than in groups 1 and 2. TIMP-3 staining exhibited an obvious increase of positive-staining rate in groups 3, 4, and 5 as compared with group 1. The positive-staining rate in group 3 (79.42%±1.35%) was about 3times that of group 1 (25.47%±5.46%, <0.01). RAdTIMP-3 can effectively protect the matrix of rabbit intervertebral disc against overloading-induced degeneration in a dose-dependent manner, resulting in the alleviation of disc degeneration.

Keywords： tissue inhibitor of metalloproteinase-3     intervertebral disc     rabbit     gene therapy    

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Role of stair-climbing test in predicting postoperative cardiopulmonary complications in elderly patients with biliary diseases

Pei-Tu REN BM, Bao-Chun LU MM, Zhi-Liang CHEN MM, Hong FU MM,

Frontiers of Medicine 2010, Volume 4, Issue 1,   Pages 77-81 doi: 10.1007/s11684-010-0005-x

Abstract: One hundred and twenty-six patients above 80 years old with biliary diseases undergoing operations in Shaoxing People’s Hospital from Jan. 2002 to Jan. 2007 were analyzed retrospectively. All patients performed a preoperative stair-climbing test, and the risks for cardiopulmonary €complications were evaluated with pair-matching and linear correlations analysis between stair-climbing height (h) and left ventricular ejective factor (EF), forced vital capacity (FVC) and forced expiratory volume in one second (FEV). There was a significant difference in the incidence of cardiopulmonary complications among different stair-climbing heights. Stair-climbing heights were positively related with EF, FVC and FEV. This suggests that the stair-climbing test is an effective and simple method for predicting cardiopulmonary complications in elderly patients with biliary diseases.

Keywords： biliary disease     cardiopulmonary complication     stair-climbing test    

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Effect of lanthanum chloride on growth of breast cancer cells and regulation of transcription

Xue LI MM , Ping HE MM , Jie XIA MM , Shiwei SONG BS , Jinhai LU BM , Yunde LIU MM ,

Frontiers of Medicine 2009, Volume 3, Issue 3,   Pages 336-340 doi: 10.1007/s11684-009-0053-2

Abstract: Lanthanum salt is a prescription drug, but its underlying functions and mechanisms are not fully understood currently. To explore the potential therapeutic value of , cytotoxicity test was applied to investigate its effects on cell proliferation. Furthermore, we observed its influence on pro-oncogene by reverse transcription polymerase chain reaction (RT-PCR). In MCF-7 cell line, repressed cell proliferation at high concentration but had no significant inhibition effect on cell growth at low concentration. However, we observed that repressed transcription at a low concentration. This may suggest that is a potent drug to inhibit the high expression of in carcinoma cells and play a clue for inhibiting the growth and invasion of tumor.

Keywords： proliferation     c-met     invasion     lanthanum chloride    

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Effect of pirfenidone on renal tubulointerstitial fibrosis

Dixin LI MM , Hongbing ZENG MD , Chunyang JI MM ,

Frontiers of Medicine 2009, Volume 3, Issue 3,   Pages 316-322 doi: 10.1007/s11684-009-0045-2

Abstract: Renal tubulointerstitial fibrosis (TIF) is the common end stage of various chronic renal diseases, and pirfenidone (PFD) is a novel, broad-spectrum anti-fibrotic compound but little is known about its effect and mechanism of action on renal TIF. In this work, we employed a unilateral ureteral obstruction (UUO) rat model to investigate the apoptosis of renal tubular epithelial cells (RTC) after PFD treatment. Thirty-five Sprague Dawley (SD) rats were randomized into three groups: sham-operated group (=7), UUO group (=14) and PFD group (=14). All rats were sacrificed at day 7 or 14 after operation. Renal histology was studied by using periodic acid schiff reagent (PAS) and Masson trichromic stain (MASSON); apoptosis was detected by terminal deoxynucleotide transferase-mediated dUTP-biotin nick end-labeling (TUNEL); tubular caspase-3 expression was assessed by immunohistochemistry. The content of malondialdehyde (MDA) and total activity of superoxide dismutase (T-SOD) in the renal cortex was determined by chemical colorimetry method. TIF, apoptosis of RTC, tubular expression of caspase-3 and the content of MDA were increased in the UUO group compared with those in the sham-operated group, and were ameliorated significantly by PFD treatment (<0.05). The activity of SOD was decreased in the UUO group, but was improved by PFD treatment (<0.05). Our results showed that PFD could ameliorate TIF in the UUO group, and the possible mechanism was by reducing the apoptosis of RTC, which involved oxidative stress and caspase-3.

Keywords： pirfenidone     apoptosis     caspase 3     oxidative stress    

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Effects of phosphatidylinositol 3-kinase inhibitor on human cervical carcinoma cells

Yuan ZHANG MD , Xiaoyan ZHANG MM , Yanhui LI MM , Xuan DU MM , Zehua WANG MD, PhD , Hongbo WANG MD ,

Frontiers of Medicine 2009, Volume 3, Issue 3,   Pages 341-346 doi: 10.1007/s11684-009-0067-9

Abstract: Phosphatidylinositol 3-kinase (PI3K) is a crucial cell survival pathway implicated in tumorigenesis because of its role in stimulating cell proliferation and suppressing apoptosis. This study was to investigate the regulation of proliferation and apoptosis by LY294002, an inhibitor of PI3K in cervical cancer cells and the expression of FLICE-like inhibitory protein (c-FLIP) . Human cervical cancer HeLa cells were used in this experiment and cultured. The cultured cells were treated with LY294002 at different concentrations (10, 25, 50 and 100µmol/L) for 6, 12, 24, and 48h before harvesting for evaluation. Cell viability was measured by 3-(4,5)-dimethylthiazol(-2-y1)-3,5-di-phenyltetrazoliumbromide (MTT) assay. Apoptosis was analyzed by flow cytometry. The expression of c-FLIP was detected by Western blot. Cell viability was inhibited by LY294002 significantly (<0.05). Flow cytometry analysis revealed that cell apoptosis was significantly increased in the presence of LY294002 as compared with the control group. Although the expression of c-FLIP was increased in a short time, the expression of c-FLIP was markedly suppressed after the treatment of LY294002 for 48h. These results suggested that the PI3K/Akt signal pathway might be involved in the regulation of cell apoptosis in cervical cancer cells. Moreover, the regulation of c-FLIP expression through PI3K/Akt signal pathway in cervical cancer cells was observed .

Keywords： human cervical cancer cells     apoptosis     phosphatidylinositol 3-kinase (PI3K)/Akt     FLICE-like inhibitory protein    

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Correlation between viral load and liver cirrhosis in chronic hepatitis B patients

Lili LIU MM , Jiyao WANG MD , Weimin SHE MM ,

Frontiers of Medicine 2009, Volume 3, Issue 3,   Pages 271-276 doi: 10.1007/s11684-009-0054-1

Abstract: The aim of this paper is to investigate the relationship between hepatitis B virus (HBV) DNA levels during the course and the progression to cirrhosis with chronic hepatitis B. A total of 239 chronic hepatitis B patients confirmed by liver biopsy between 2001 and 2007 were followed up for a median of 28 months. Compared with the patients without cirrhosis, the patients progressed to cirrhosis were older and with higher HBV-DNA levels at end point. However, there was no significant difference in cirrhosis progression between different HBV-DNA groups at baseline ( = 0.531). Kaplan-Meier analysis showed higher HBV-DNA level at endpoint had increasing risk of cirrhosis ( = 0.019). The results of Cox model indicated that HBV-DNA levels at endpoint, stage of fibrosis, negative hepatitis B e antigen, and γ-glutamyl transpeptidase at baseline were independent risk factors of cirrhosis. The relative risk ratios were 1.898, 1.918, 8.976, and 1.006, respectively. Progression to cirrhosis in chronic hepatitis B patients is correlated with HBV-DNA levels during follow-up.

Keywords： hepatitis B     chronic     viral load     liver cirrhosis    

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The role of CDK1 siRNA interference in cell cycle and cell apoptosis

Hui XIAO PhD, Ming TIAN MM, Junna GE MM, Xin Wei MD, Zhaoming LI MM, Xiaolan LI MS, Deding TAO PhD, Junbo

Frontiers of Medicine 2009, Volume 3, Issue 4,   Pages 384-389 doi: 10.1007/s11684-009-0070-1

Abstract: In the present report, cyclin-dependent kinase1 (CDK1) siRNA was transfected into cells to silence the CDK1 gene expression and study its role in the cell cycle and cell apoptosis. The siRNA targeting CDK1 gene was chemically synthesized and transfected into Hela cells by lipofectamine 2000. The expression levels of CDK1 gene and protein were examined by real-time quantitative polymerase chain reaction (PCR) and Western blot, respectively. The cell cycle was analyzed by using DNA content analysis by flow cytometry. Cell apoptosis was detected by the Annexin V/PI method. The morphological changes of transfected cells were examined under the microscopy by Wright-Giemsa stain. CDK1 gene was successfully silenced by its siRNA, and the CDK1 protein expression level was decreased significantly, especially from 48thh to 60thh after transfection. The DNA content analysis showed that transfection of CDK1 siRNA led to cells accumulating in G/M phase. There was no significant difference in the apoptotic rate between transfected cells and the control cells after transfection of CDK1 siRNA for 48 or 60h. More double nucleus or multinucleus cells could be seen under the microscopy among the transfected cells. The decreased CDK1 expression by siRNA silencing gave rise to cell cycle arrest in G/M phase but did not induce apoptosis.

Keywords： cyclin-dependent kinase1     siRNA interference     cell cycle     apoptosis    

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The next step of community health construction: Training general practitioners and implementing health management

Kan ZHANG MM, Wei DONG MM, Ying-Yao CHEN MD,

Frontiers of Medicine 2010, Volume 4, Issue 2,   Pages 134-138 doi: 10.1007/s11684-010-0041-6

Abstract: This article discusses the concept of health management and stresses that community health management should be the starting point of community health service, necessitating a paradigm shift from observing the treatment-oriented medical model to observing the prevention-and-health management-based medical model. Community health construction has entered a new phase, one which highlights the need to train general practitioners in practice-based life cycle health management. In addition, general practitioners should assume the mission of implementing community health management.

Keywords： community health     general practitioners     health management    

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Preliminary results of gentamycin combined with sodium bicarbonate for prevention of irinotecan-induced diarrhea

Qi MEI MM, Zhe CAO MM, Hua XIONG MD, Yuan CHEN MD,

Frontiers of Medicine 2009, Volume 3, Issue 4,   Pages 470-474 doi: 10.1007/s11684-009-0077-7

Abstract: The aim of this paper was to observe the clinical effect of gentamycin combined with sodium bicarbonate for the prevention of irinotecan-induced diarrhea. A total of 98 patients with stage IV cancers were recruited and divided into a prevention group (52 patients) and a control group (46 patients). All patients received the chemotherapy including irinotecan. The prevention group received gentamycin and sodium bicarbonate before the use of irinotecan for 4 days; the control group did not receive any prevention. The use of gentamycin and sodium bicarbonate resulted in significantly higher stool pH ( < 0.001), while the incidence of diarrhea by irinotecan was reduced (prevention group 13.70% control group 34.83%; < 0.001). Gentamycin combined with sodium bicarbonate appears to be useful in preventing the diarrhea induced by irinotecan and reducing the dosage of loperamide and fluid replacement.

Keywords： irinotecan     diarrhea     gentamycin     sodium bicarbonate     prevention    

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Effect of PRAK gene knockout on the proliferation of mouse embryonic fibroblasts

Xiaowei GONG MD, PhD, Xiaoyan MING MD, Xu WANG MM, Daan WANG MD, Peng DENG MM, Yong JIANG MD, PhD, Aihua

Frontiers of Medicine 2009, Volume 3, Issue 4,   Pages 379-383 doi: 10.1007/s11684-009-0073-y

Abstract: p38 regulated/activated protein kinase (PRAK) plays a key role in cell senescence and tumor suppression. The aim of this study was to investigate if PRAK had effect on cell proliferation. The growth of and mouse embryonic fibroblast (MEF) cells was measured by methylthiazoletetrazolium (MTT) colorimetric assay, and the proportion of the cell number in different phases of the cell cycle was analyzed by flow cytometry. The growth curves showed that the growth rate was notably decreased, and cell double time was elongated in cells; moreover, the number of cells was decreased by 44.5% compared with that of cells cultured for 96h, suggesting that G/M transition is inhibited in cells. Meanwhile, G/S transition was also inhibited in cells, observed with flow cytometry analysis. The ratios of G/G, G/M, and S phases of cells were 44.9%, 12.2%, and 42.9%, respectively, while those of cells were 55.3%, 7.3%, and 37.4%, respectively. There were 23.1% increase and 12.7% decrease of the number of cells in G and S phases comparison with that of cells, respectively. Taken together, gene knockout in MEF cells leads to cell cycle arrest and proliferation inhibition.

Keywords： p38 regulated/activated protein kinase     gene knockout     cell cycle     cell proliferation    

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MicroRNAs and hepatitis viruses

Gang LI MD , Xiaojia XIONG MM ,

Frontiers of Medicine 2009, Volume 3, Issue 3,   Pages 265-270 doi: 10.1007/s11684-009-0055-0

Abstract: MicroRNAs (miRNAs) are a class of small RNA molecules. They play a pivotal role in diverse domains such as infection, tumorigenesis, and immune reaction. As key regulators of most genes’ expression, they react at posttranscriptional level. It is increasingly clear that miRNAs are necessary for physiological and pathological processes. In the past few years, investigators gradually brought the concept of miRNA into studies of viral infection, including hepatitis viruses. The hepatitis B and C viruses are common causes of liver disease worldwide. It is very difficult to cure chronic hepatitis due to drug resistance during antivirus therapy. Elucidating the mechanisms of virus-host interactions in hepatitis B and C is very important in diagnosis, prognosis, and therapy. This article reviews the current knowledge of viral hepatitis (B and C type) at the level of miRNA and tries to outline areas of potential studies.

Keywords： microRNA     hepatitis B virus     hepatitis C virus    

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450 mm Silicon Wafers Are Imperative for Moore's Law but maybe Postponed

Hailing Tu

Engineering 2015, Volume 1, Issue 2,   Pages 162-163 doi: 10.15302/J-ENG-2015060

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Protective effect of tanshinone II A on signal transduction system protein kinase B in rats with myocardial hypertrophy

Enyuan TU MD, Yongjun PAN MM, Kang ZHENG MM, Zhaohua WANG MD, Qiansheng LIANG MD, Guangtian YANG MD,

Frontiers of Medicine 2009, Volume 3, Issue 4,   Pages 431-436 doi: 10.1007/s11684-009-0088-4

Abstract: The effects of tanshinone II A on cell signal transduction system protein kinase B in rats with myocardial hypertrophy induced by the abdominal aorta partial coarctation were investigated. Rat models of myocardial hypertrophy were established by using abdominal aorta partial coarctation method. Forty-eight rats were randomly divided into sham group (S group), model group (M group), valsartan treatment group (X group), low-dose tanshinone treatment group (LD group), medium-dose tanshinone treatment group (MD group), and high-dose tanshinone treatment group (HD group) (=8 in each group). Left ventricular mass index (LVMI), left ventricular posterior wall (LVPW), and septal thickness (IVS) were detected by high frequency ultrasonography. Myocardial fiber diameter (MFD) was examined by Hematoxylin-Eosin (HE) staining, and the contents of phosphorylated protein kinase B (p-Akt) and p-Gsk3β in myocardium were assayed by Western blot. The results showed that compared with S group, the values of LVMI, LVPW, IVS and MFD were increased in other groups (<0.05), and the contents of p-Akt, and p-Gsk3β were also increased in other groups. As compared with MD group, the values of LVMI, LVPW, IVS and MFD were decreased in all treatment groups (<0.05), and the contents of p-Akt, and p-Gsk3β were also decreased in all treatment groups. However, there were no significant differences among LD, MD, and HD groups (>0.05), and there were no significant differences between X group and tanshinone treatment groups (>0.05). It was suggested that tanshinone II A could prevent myocardial hypertrophy by its action on the Akt signaling pathway.

Keywords： tanshinone II A     myocardial hypertrophy     rat     protein kinase B     abdominal aorta coarctation    

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Assessment of global and regional left ventricular twist and displacement in anterior myocardial infarction using 2-dimensional strain imaging

Wei HAN MM, Ming-Xing XIE MD, Qing LV MD, Xin-Fang WANG MD, Li ZHANG MM,

Frontiers of Medicine 2010, Volume 4, Issue 1,   Pages 71-76 doi: 10.1007/s11684-010-0006-9

Abstract: The recent development of 2-dimensional strain (2D strain) imaging can provide a powerful alternative for assessing left ventricular (LV) torsion. This study was conducted to evaluate the global and regional left ventricular twist by 2D strain in patients with anterior wall myocardial infarction (AMI). A total of 55 AMI patients were divided into two groups according to their ejection fraction (EF) values (group A: LVEF≥50%; group B: LVEF<50%), and 35 normal people served as the control group. Using 2-dimensional strain software, global and regional LV rotation and displacement were obtained at two planes. Compared with the control group, patients of group A showed reduced peak LV twist of the anterior and anterior-septal wall (9.26±1.89 10.74±2.67; 9.71±1.71 11.36±2.29, both <0.05), but the radial displacement and global twist were maintained (>0.05). Differently, regional and global LV twist and radial displacement in patients of group B deceased significantly, especially in the anterior and anterior-septal wall, as compared with patients in the control or group A (both <0.05). Moreover, a strong correlation was noted between peak twist and radial displacement; the twist-displacement loop was markedly distorted in patients of group B. This study demonstrated that 2D strain has a potential ability for quantification of left ventricular global and segment twist and radial displacement in patients with coronary artery disease.

Keywords： echocardiography     twist     two-dimensional strain imaging     coronary artery disease    

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Data mining of microarray for differentially expressed genes in liver metastasis from gastric cancer

Ling XU MM, Feng WANG MM, Xuan-Fu XU MD, Wen-Hui MO BM, Rong WAN MD, Chuan-Yong GUO MD, Xing-Peng WANG

Frontiers of Medicine 2010, Volume 4, Issue 2,   Pages 247-253 doi: 10.1007/s11684-010-0027-4

Abstract: Tumor metastasis is the leading cause of death for gastric cancer. Metastasis is the main reason for the failure of clinical treatment for gastric cancer. In order to find metastasis-related genes and abnormal signal transduction pathway of high-invasive gastric cancer, samples of gastric cancer with liver metastasis were collected for microarray detection; up-regulated or down-regulated genes in all three cases were simultaneously screened out. Subsequently, from the preliminary screened genes, molecular pathways possibly impacting liver metastasis from gastric cancer were investigated by the Gene Cluster with Literature Profiles (GenCLip) analysis software. Many biological effects including apoptosis have been validated. Functional analysis of differentially expressed genes revealed that a variety of biological pathways, such as blood circulation and gas exchange, vasodilation and vasoconstriction regulation, and immune defense, could be significantly activated. Besides, gene sequences, specific keywords or gene regulatory networks were further searched by GenCLiP. We conclude that data mining allows to quickly identify a series of special signal transduction pathways involving abnormally expressed genes.

Keywords： gastric carcinoma     metastasis     signal transduction     gene chips    

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Title Author Date Type Operation

Adenovirus-mediated tissue inhibitor of metalloproteinase-3 gene transfection inhibits rabbit intervertebral disc degeneration in vivo

Xudong YU MM, Zengwu SHAO MD, Liming XIONG MD, Weiwei XU MM, Hezhong WANG MM, Huifa XU MM,

Journal Article

Role of stair-climbing test in predicting postoperative cardiopulmonary complications in elderly patients with biliary diseases

Pei-Tu REN BM, Bao-Chun LU MM, Zhi-Liang CHEN MM, Hong FU MM,

Journal Article

Effect of lanthanum chloride on growth of breast cancer cells and regulation of transcription

Xue LI MM , Ping HE MM , Jie XIA MM , Shiwei SONG BS , Jinhai LU BM , Yunde LIU MM ,

Journal Article

Effect of pirfenidone on renal tubulointerstitial fibrosis

Dixin LI MM , Hongbing ZENG MD , Chunyang JI MM ,

Journal Article

Effects of phosphatidylinositol 3-kinase inhibitor on human cervical carcinoma cells

Yuan ZHANG MD , Xiaoyan ZHANG MM , Yanhui LI MM , Xuan DU MM , Zehua WANG MD, PhD , Hongbo WANG MD ,

Journal Article

Correlation between viral load and liver cirrhosis in chronic hepatitis B patients

Lili LIU MM , Jiyao WANG MD , Weimin SHE MM ,

Journal Article

The role of CDK1 siRNA interference in cell cycle and cell apoptosis

Hui XIAO PhD, Ming TIAN MM, Junna GE MM, Xin Wei MD, Zhaoming LI MM, Xiaolan LI MS, Deding TAO PhD, Junbo

Journal Article

The next step of community health construction: Training general practitioners and implementing health management

Kan ZHANG MM, Wei DONG MM, Ying-Yao CHEN MD,

Journal Article

Preliminary results of gentamycin combined with sodium bicarbonate for prevention of irinotecan-induced diarrhea

Qi MEI MM, Zhe CAO MM, Hua XIONG MD, Yuan CHEN MD,

Journal Article

Effect of PRAK gene knockout on the proliferation of mouse embryonic fibroblasts

Xiaowei GONG MD, PhD, Xiaoyan MING MD, Xu WANG MM, Daan WANG MD, Peng DENG MM, Yong JIANG MD, PhD, Aihua

Journal Article

MicroRNAs and hepatitis viruses

Gang LI MD , Xiaojia XIONG MM ,

Journal Article

450 mm Silicon Wafers Are Imperative for Moore's Law but maybe Postponed

Hailing Tu

Journal Article

Protective effect of tanshinone II A on signal transduction system protein kinase B in rats with myocardial hypertrophy

Enyuan TU MD, Yongjun PAN MM, Kang ZHENG MM, Zhaohua WANG MD, Qiansheng LIANG MD, Guangtian YANG MD,

Journal Article

Assessment of global and regional left ventricular twist and displacement in anterior myocardial infarction using 2-dimensional strain imaging

Wei HAN MM, Ming-Xing XIE MD, Qing LV MD, Xin-Fang WANG MD, Li ZHANG MM,

Journal Article

Data mining of microarray for differentially expressed genes in liver metastasis from gastric cancer

Ling XU MM, Feng WANG MM, Xuan-Fu XU MD, Wen-Hui MO BM, Rong WAN MD, Chuan-Yong GUO MD, Xing-Peng WANG

Journal Article