ONYX-015 and H101 are E1B 55-kDa protein-deficient replicating C group adenoviruses that are currently in clinical trials as antitumor agents. However, their application in cancer gene therapy is limited by the native tropism of C group adenoviruses. This is in part due to low expression of the C group adenovirus receptor (coxsackievirus-adenovirus receptor, CAR) on malignant tumors. An H101-based chimeric virus vector containing sequences encoding the Ad35 fiber domain instead of the Ad5 fiber (H101-F35) was constructed. This modification allowed infection of tumor cells through CD46, a membrane protein over-expressed on tumors. The CAR and CD46 RNA expression was evaluated by RT-PCR method. H101-F35 conferred a stronger cytocidal effect than H101 and ONYX-015 in tumor cell lines that lacked CAR expression (MDA-MB-435 and MCF-7), while the cytocidal effect of H101-35, H101 and ONYX-015 was similar in high-level CAR expressing cancer cell lines (A549, NCI-H446, Hep3B, LNCaP, ZR-75-30 and Bcap-37). In an MDA-MB-435 xenograft mouse tumor model, tumor growth in mice receiving H101-F35 was significantly inhibited compared with mice injected with H101. These results suggest that the chimeric oncolytic adenovirus H101-F35 vector might be a useful candidate for gene therapy of cancer.

OBJECTIVETo compare the spatiotemporal pattern of event-related potentials (ERPs) of relational memory retention between color-location binding and semantics-location binding.

METHODSThe ERPs of 19 channels were recorded from 14 healthy subjects while performing the two binding delayed-match-to-sample tasks. A paired-sample t test was used for analysis of both the behavioral performance and ERPs, and statistical parametric mapping (SPM) of the t values was applied to ERPs.

RESULTSBehavioral performances (reaction time and accuracy) in color-location binding were significant better than those of semantics-location binding. The SPM(t) of the ERPs showed significant effects in the middle frontal region and most areas of the parietal lobe (about 200 ms), the bilateral prefrontal and frontal regions (260 approximately 320 ms), and the left occipital region (500 approximately 580 ms).

CONCLUSIONRetention of semantics-location relation involves more brain regions than that of color-location relation, and the largest effect occurs in the frontal region.

Electroencephalography ; Event-Related Potentials, P300 ; physiology ; Frontal Lobe ; physiology ; Humans ; Memory ; physiology ; Retention (Psychology) ; physiology ; Task Performance and Analysis

Amnion ; cytology ; Animals ; Brain Injuries ; therapy ; Cell Transplantation ; Cells, Cultured ; Female ; Hindlimb ; physiology ; Humans ; Rats ; Rats, Sprague-Dawley ; Transplantation, Heterologous

Objective To analyze the correlation between SF-36 and QOL-35 and the consistency of the two kinds of life-quality questionnaires when evaluating the quality of life in patients with coronary heart disease. Methods 781 in-hospital-patients, who underwent coronary angiography from June 2008 to April 2009, were included in this study. Quality of life was measured by the Chinese versions of SF-36 and QOL-35. Demographic and clinical information were collected.Correlation Analysis was done between SF-36 and QOL-35 in the patients with coronary artery disease. Results The total score of SF-36 was 62.63 ± 12.47 and the QOL-35 total score was 62.70 ± 9.69. Data from the simple correlation analysis showed that SF-36 and QOL-35 total scores (r=0.725, P＜0.01 ), SF-36 physical functioning and QOL-35 independent living capacity (r=0.933, P＜0.01), SF-36 mental health and QOL-35 mental health (r=0.132, P＜0.01), SF-36 social function and QOL-35 social function score (r=0.215, P＜0.01 ) were all relevant. Canonical correlation analysis showed that there was significant correlation between SF-36 and QOL-35 (r=0.946, P＜0.01 ). Conclusion SF-36 and QOL-35 were consistent in the evaluation on the quality of life, at the overall level.

Xi'an Jiaotong University has proposed the concept of "less teaching and more learning, interaction between guiding and learning" in medical education, based on its sedimentary deposits, and carried out reform for all clinical medical students since 2001. After more than ten years of educational reform, we have built brand new management framework, and established integrated organ system-based curriculum and PBL teaching pattern. This pattern involves eight aspects of comprehensive reform, including training program, curriculum model, textbook, teaching method, learning style, assessment and evaluation, teaching organization, teaching conditions and guarantee. It will provide paradigm for the integrated curriculum reform in peer colleges, and will be a milestone in the history of medical education in China.

BACKGROUNDEvidence indicates that early reperfusion therapy in patients with ST-elevation myocardial infarction (STEMI) reduces complications. This study was undertaken to compare the in-hospital delay to primary percutaneous coronary intervention (PPCI) for patients with STEMI between specialized hospitals and non-specialized hospitals in Beijing, China.

METHODSTwo specialized hospitals and fifteen non-specialized hospitals capable of performing PPCI were selected to participate in this study. A total of 308 patients, within 12 hours of the onset of symptoms and undergoing PPCI between November 1, 2005 and December 31, 2006 were enrolled. Data were collected by structured interview and review of medical records.

RESULTSThe median in-hospital delay was 98 (interquartile range 105 to 180) minutes, and 16.9% of the patients were treated within 90 minutes. Total in-hospital delay and ECG-to-treatment decision-making time were longer in the non-specialized hospitals than in the cardiac specialized hospitals (147 minutes vs. 120 minutes, P < 0.001; 55 minutes vs. 45 minutes, P = 0.035). After controlling the confounding factors, the non-specialized hospitals were independently associated with an increased risk of being in the upper median of in-hospital delays.

CONCLUSIONSThere were substantial in-hospital delays between arrival at the hospital and the administration of PPCI for patients with STEMI in Beijing. Patients admitted to the cardiac specialized hospitals had a shorter in-hospital delay than those to the non-specialized hospitals because of a shorter time of ECG-to-treatment decision-making.

Angioplasty, Balloon, Coronary ; China ; Decision Making ; Electrocardiography ; Female ; Hospitals ; statistics & numerical data ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; therapy ; Quality of Health Care ; Time Factors ; Treatment Outcome

OBJECTIVETo investigate nestin activation in rat brain subjected to ischemia-reperfusion injury and its changes in response to Tongxinluo treatment.

METHODSCerebral ischemia was induced by temporary middle cerebral artery occlusion (MCAO) in rats. At 3, 7, 14 and 21 days after MCAO, nestin expression in the ependyma, subventricular zone (SVZ), hippocampal subdentate gyrus zone (HDG) of the rats treated with Tongxinluo were guantified by immunohistochemistry.

RESULTSCompared with the sham operation group, nestin was significantly increased 7, 14 and 21 days after MCAO (P<0.05), and immunofluorescence of BrdU+nestin-positive neurons significantly increased in the SVZ. After treatment with Tongxinluo, the number of BrdU-positive neurons and BrdU+nestin-positive neurons significantly increased as compared with MCAO group (P<0.05).

CONCLUSIONFocal cerebral ischemia in the rat results in rapid response and proliferation of neural stem cells in the SVZ and HDG in the ischemic hemisphere, and Tongxinluo may enhance the differentiation and proliferation capacity of the neural stem cells after MCAO.

Animals ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; therapeutic use ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; drug therapy ; metabolism ; Intermediate Filament Proteins ; metabolism ; Male ; Nerve Tissue Proteins ; metabolism ; Nestin ; Neurons ; cytology ; drug effects ; metabolism ; Phytotherapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; metabolism ; Stem Cells ; cytology ; drug effects ; metabolism ; Time Factors

OBJECTIVETo investigate the pathological characteristics of heroin spongiform leukoencephalopathy (HSLE).

METHODSCerebral tissue specimens were obtained from 15 patients with HSLE and the histological observations under optical and electron microscopes were carried out by HE, Bielschowsky's, and chromotrope 2R-brilliant green staining.

RESULTSHSLE was characterized primarily by spongiform vacuolar degeneration of the cerebral white matter. Neurons in the gray matter, Purkinje and granular cells in the cerebella remain intact in all the cases. Numerous vacuoles, which merged to form larger cavities, appeared in the damaged white matter, and the axons survived in the deep white matter. The myelin sheath in the cerebellar white matter sustained more severe damages than those in the cerebral white matter. No vacuoles or lymphocyte infiltration occurred in the small peripheral vessels.

CONCLUSIONHSLE is pathologically characterized by vacuolar degeneration due to primary damage of the myelin, and the spongiform vacuolar degeneration is closely associated with the severity of demyelination in the white matter.

Adult ; Autopsy ; Canavan Disease ; etiology ; pathology ; Cerebellum ; chemistry ; pathology ; ultrastructure ; Cerebral Cortex ; chemistry ; pathology ; ultrastructure ; Female ; Heroin Dependence ; complications ; Humans ; Male ; Microscopy, Electron ; Middle Aged ; Neurons ; chemistry ; pathology ; Purkinje Cells ; chemistry ; pathology ; Staining and Labeling ; methods ; Young Adult

OBJECTIVETo establish a flow cytometric method to detect the alteration of phenotypes and concentration of circulating microvesicles (MVs) from myocardial ischemic preconditioning (IPC) treated rats (IPC-MVs), and to investigate the effects of IPC-MVs on ischemia/reperfusion (I/R) injury in rats.

METHODSMyocardial IPC was elicited by three.cycles of 5-min ischemia and 5-min reperfusion of the left anterior descending (LAD) coronary artery. Platelet-free plasma (PFP) was isolated through two steps of centrifugation at room temperature from the peripheral blood, and IPC-MVs were isolated by ultracentrifugation from PFR PFP was incubated with anti-CD61, anti-CD144, anti-CD45 and anti-Erythroid Cells, and added 1, 2 µm latex beads to calibrate and absolutely count by flow cytometry. For functional research, I/R injury was induced by 30-min ischemia and 120-min reperfusion of LAD. IPC-MVs 7 mg/kg were infused via the femoral vein in myocardial I/R injured rats. Mean arterial blood pressure (MAP), heart rate (HR) and ST-segment of electro-cardiogram (ECG) were monitored throughout the experiment. Changes of myocardial morphology were observed after hematoxylin-eosin (HE) staining. The activity of plasma lactate dehydrogenase (LDH) was tested by Microplate Reader. Myocardial infarct size was measured by TTC staining.

RESULTSTotal IPC-MVs and different phenotypes, including platelet-derived MVs (PMVs), endothelial cell-derived MVs (EMVs), leucocyte-derived MVs (LMVs) and erythrocyte-derived MVs (RMVs) were all isolated which were identified membrane vesicles (<1 Vm) with corresponding antibody positive. The numbers of PMVs, EMVs and RMVs were significantly increased in circulation of IPC treated rats (P<0.05, respectively). In addition, at the end of 120-min reperfusion in I/R injured rats, IPC-MVs markedly increased HR (P<0.01), decreased ST-segment and LDH activity (P < 0.05, P < 0.01). The damage of myocardium was obviously alleviated and myocardial infarct size was significantly lowered after IPC-MVs treatment (P < 0.01).

CONCLUSIONThe method of flow cytometry was successfully established to detect the phenotypes and concentration alteration of IPC-MVs, including PMVs, EMVs, LMVs and RMVs. Furthermore, circulating IPC-MVs protected myocardium against I/R injury in rats.

Animals ; Cell-Derived Microparticles ; metabolism ; Coronary Vessels ; pathology ; Flow Cytometry ; Heart Rate ; Ischemic Preconditioning, Myocardial ; Myocardial Infarction ; physiopathology ; Myocardial Reperfusion Injury ; physiopathology ; Myocardium ; pathology ; Phenotype ; Rats

OBJECTIVETo investigate the effects of microvesicles (MVs) derived from hypoxia/reoxygenation (H/R)-treated human umbilical vein endothelial cells (HUVECs) on endothelium-dependent relaxation of rat thoracic aortic rings.

METHODSH/R injury model was established to induce HUVECs to release H/R-EMVs. H/R-EMVs from HUVECs were isolated by ultracentrifugation from the conditioned culture medium. H/R-EMVs were characterized using 1 μm latex beads and anti-PE-CD144 by flow cytometry. Thoracic aortic rings of rats were incubated with 2.5, 5, 10, 20 μg/ml H/R-EMVs derived from H/R-treated HUVECs for 4 hours, and their endothelium-dependent relaxation in response to acetylcholine (ACh) or endothelium-independent relaxation in response to sodium nitroprusside (SNP) was recorded in vitro. The nitric oxide (NO) production of ACh-treated thoracic aortic rings of rats was measured using Griess reagent. The expression of endothelial NO synthase (eNOS) and phosphorylated eNOS (p-eNOS, Ser-1177) in the thoracic aortic rings of rats was detected by Western blotting. Furthermore, the levels of SOD and MDA in H/R-EMVs-treated thoracic aortic rings of rats were measured using SOD and MDA kit.

RESULTSH/R-EMVs were induced by H/R-treated HUVECs and isolated by ultracentrifugation. The membrane vesicles (< 1 μm) induced by H/R were CD144 positive. ACh-induced relaxation and NO production of rat thoracic aortic rings were impaired by H/R-EMVs treatment in a concentration-dependent manner (P < 0.05, P < 0.01). The expression of total eNOS (t-eNOS) was not affected by H/R-EMVs. However, the expression of p-eNOS decreased after treated with H/R-EMVs. The activity of SOD decreased and the level of MDA increased in H/R-EMVs treated rat thoracic aortic rings (P < 0.01).

CONCLUSIONACh induced endothelium-dependent relaxation of thoracic aortic rings of rats was impaired by H/R-EMVs in a concentration-dependent manner. The mechanisms included a decrease in NO production, p-eNOS expression and an increase in oxidative stress.

Acetylcholine ; pharmacology ; Animals ; Aorta, Thoracic ; physiology ; Cell Hypoxia ; Endothelium, Vascular ; physiology ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; In Vitro Techniques ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Nitroprusside ; pharmacology ; Oxidative Stress ; Rats