The present study demonstrates that it is feasible to safely use an adenovirus gene-transfer vector to deliver the human hepatocyte growth factor gene to individuals with clinically significant coronary artery disease by direct intracoronary injection. However, a great deal of additional work must be done before administration of Ad-HGF can be recommended for clinical practice.
Aim: To study the effect of adenovirus 5 -mediated human hepatocyte growth factor (Ad 5 -HGF) transfer on post-infarct heart failure in a swine model. Methods: Twelve young Suzhong swine were randomly divided into 2 groups: the Ad 5 -HGF group (n=6) and the null-Ad 5 group (n=6). Four weeks after left anterior descending coronary artery (LAD) ligation, Ad 5 -HGF was transferred into the myocardium via the right coronary artery. Coronary angiography and gated cardiac perfusion imaging were performed at the end of 4 and 7 weeks after LAD ligation, respectively, to evaluate collateral artery growth and cardiac perfusion. Then all animals were killed, the expression of HGF and α-smooth muscle actin (α-SMA) were evaluated by enzyme-linked immunosorbent assay and immunohistochemistry. .01) were improved in the Ad 5 -HGF group. Cardiac perfusion was significantly improved in the Ad 5 -HGF group. In the Ad 5 -HGF group, growth of collateral arteries was obviously greater (average rank sum 9.17 vs 3. 83, n=6, u=-2.687, P<0.01), and the number of α-SMA + vessels/mm 2 was significantly greater (56.1±4.2 vs 16.4±3.5, t=17.731, P< 0.01) than in the null-Ad 5 group. Conclusion: High expression levels of human HGF were observed in the myocardium because of non-infarct-related vessel transfer. HGF can increase the number of functional arterioles and improve collateral artery growth. HGF can improve cardiac perfusion and heart function.
We aim to study the amelioration effect of adenovirus5-mediated human hepatocyte growth factor gene transfer on postinfarction heart failure in swine model. Twelve Suzhong young swine were randomly divided into 2 groups of 6 pigs each: Ad(5)-HGF group and mock-vector Ad(5) group. Four weeks after ligation of the left anterior descending coronary artery, Ad(5)-HGF was intracoronarily transferred into the myocardium. Simultaneously, gate cardiac perfusion imaging was performed to evaluate the heart function. Three weeks later, gate cardiac perfusion imaging was performed again, then the hearts were removed and sectioned for immunohistochemical examination to illustrate the effects of Ad(5)-HGF on infarcted myocardium. The expression of HGF was examined by ELISA. The results were: (1) compared with the mock-vector Ad(5) group, high expression of human HGF was observed in the myocardium of Ad(5)-HGF group; (2) in the Ad(5)-HGF group, the number of CD117(+) cells co-expressing c-Met per mm(2) was significantly larger; (3) the improvement in LVEF was greater in the Ad(5)-HGF group than in the mock-vector Ad(5) group. We concluded that: (1) high expression of human HGF was observed in the myocardium through intracoronary gene transfection; (2) HGF can improve the mobilization of CD117(+)/c-Met(+) stem cells into ischemic myocardium. The amelioration effect of HGF on postinfarction heart failure could not be limited to stimulating angiogenesis, anti-apoptosis, anti-fibrosis, but was also involved in the recruitment of stem cells into myocardium.
Growth factor gene transfer-induced therapeutic angiogenesis has become a novel approach for the treatment of myocardial ischemia. In order to provide a basis for the clinical application of an adenovirus with hepatocyte growth factor gene (Ad-HGF) in the treatment of myocardial ischemia, we established a minipig model of chronically ischemic myocardium in which an Ameroid constrictor was placed around the left circumflex branch of the coronary artery (LCX). A total of 18 minipigs were randomly divided into 3 groups: a surgery control group, a model group and an Ad-HGF treatment group implanted with Ameroid constrictor. Ad-HGF or the control agent was injected directly into the ischemic myocardium, and an improvement in heart function and blood supply were evaluated. The results showed that myocardial perfusion remarkably improved in the Ad-HGF group compared with that in both the control and model groups. Four weeks after the treatment, the density of newly formed blood vessels was higher and the number of collateral blood vessels was greater in the Ad-HGF group than in the model group. The area of myocardial ischemia reduced evidently and the left ventricular ejection fraction improved significantly in the Ad-HGF group. These results suggest that HGF gene therapy may become a novel approach in the treatment of chronically ischemic myocardium.
The Baoxingchang Cu-Mo deposit is an important deposit in the Jinshajiang-Red River alkali-rich porphyry area, Western Yunnan. Fluid inclusion petrography and inclusion microscopic thermometric analysis of quartz phenocrysts in non-mineralized porphyritic granite, lamprophyre quartz veins, molybdenite quartz veins, copper-pyrite-molybdenite quartz veins, and pyrite quartz veins show that the development in primary inclusion of quartz phenocrysts and quartz veins can include vapour-rich inclusions and liquid-rich inclusions. Fluid inclusions are characterised by their medium-high temperature and moderate salinity. However, the temperature and salinity of non-mineralised quartz fluid inclusions are higher than those of quartz fluid inclusions in the mineralisation stage. Captured pressure and mineralisation depth during mineralisation reveal that the copper-molybdenum deposit is formed in hypabyssal environment, which is consistent with porphyry metalloginic systems.
In response to rapidly growing and diversifying traffic demand, it is necessary to develop a network partitioning method that could achieve real-time global optimal performance and adapt to traffic network evolution. In this paper, an adaptive partitioning method is presented, which achieves optimal partitions at runtime and determines appropriate Time-of-Day breakpoints to update partition results simultaneously. For each time interval, partitioning schemes are firstly assessed in terms of modularity by taking roadway geometry, real-time traffic flow information, and signal timing into account. Two values are attained from the assessment: the maximum modularity of the optimal partition and the modularity obtained from the existing partition. Then the existing partition is updated, provided that the relative deviation of these two values exceeds a given threshold for a certain number of successive time intervals. Experimental results show that the above-mentioned partitioning scheme outperforms some notable traffic control techniques in modularity in the spatial aspect. In the temporal aspect, the updating scheme can well respond to varying traffic conditions and yield significantly higher average modularity.
To improve the operating efficiency of the bus transport system and service level to the public, the scheduling optimization of single-line bus route for express bus and shuttle bus was carried out during the rush hours. Based on the relevant basic assumptions, this paper established the parking judgment model and passenger ride selection model of express bus and shuttle bus. Meanwhile, taking passenger ride experience and bus company operating cost as the objective function, genetic algorithm was used to optimize the bus departure interval. In the optimization process, two schemes including discrete scheme and continuous scheme were provided. The models and optimization methods were applied to an actual single line bus route. The results show that, the discrete scheme has faster convergence speed and better optimization effect. The value of objective function decreases by 12.38%. Although the bus operation cost has increased slightly, considering the public commonweal of the bus transport system, the optimization results are still in line with the essence of its operation. The models and its optimization methods can provide a reference for the scheduling optimization of single-line bus route with the introduction of express bus and shuttle bus.
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