With the development of molecular and cellar cardiology, gene therapy to cardiovascular disease has become the hot spot and the direction of study. Now, preclinical studies on ultrasound-mediated gene delivery (UMGD) in cardiovascular disease have achieved some success, but it is still hindered by a series of practical challenges for clinical translation. Even so, UMGD still holds the promise to cardiovascular disease in gene therapy for its non-invasiveness, accuracy, safety and ability to deliver multiple genes with repeated deliveries. In this review, we will focus on the basic principle, the current development, the future prospect and drawbacks of UMGD in the therapeutic applications of cardiovascular disease.
ObjectiveTo summarize our experience of surgical treatment for right pulmonary artery originated from the ascending aorta by using adult diameter artificial vascular and study the operative indication, design, method, and therapeutic efficacy. MethodsWe retrospectively analyzed clinical data of 11 patients with right pulmonary artery originated from ascending aorta in The Second Affiliated Hospital of Harbin Medical University from May 2008 through December 2013, who were treated by using adult diameter artificial vascular. The patients ranged from 4 months to 25 months old, weighted 4-15 kg. Among of them, 4 patients had persistent truncus arteriosus and 7 had aortopulmonary septal defect. All patients were complicated with moderate pulmonary hypertension. All the patients underwent one stage surgical repair under extracorporeal circulation and cardiac arrest. During the surgery, end to side anastomosis was done between the right pulmonary artery and 16-18 mm diameter artificial blood vessels. And artificial blood vessel was connected to the main pulmonary artery or right ventricle outflow tract incision from the aorta above. ResultsThe average operation time was 179-325 (224±68) min. The average cardiopulmonary bypass (CPB) time was 81-208 (117±54) min. The average aortic clamping time was 29-63(42±21) min. The mean residence time in ICU was 71-197 (109±42) hours. The average assisted mechanical ventilator time was 59-191 (91±26) hours. The average length of stay in hospital was 21-39 (28±11) days. Low cardiac output syndromes caused by pulmonary arterial hypertension occurred in 5 patients including 2 deaths and 3 patients with good recovery by reducing the pulmonary arterial pressure and peritoneal dialysis. The result of postoperative cardiac color ultrasound examination of 9 survival patients showed vascular prosthesis, no distortion, no stenosis of the anastomosis, deformity correction satisfaction. Nine patients were followed up for 3-60 months. The results of echocardiography showed no anastomosis and artificial vascular stenosis, and the pulmonary arterial pressure decreased significantly. ConclusionThe right pulmonary artery originated from the ascending aorta in children should be operated as soon as possible. Compared the adult diameter artificial vascular treatment for one stage repair of right pulmonary artery from the ascending aorta with other operation methods, both short-term and long-term effects are good. Postoperative low cardiac output syndrome is a common complication.
Skin aging principles play important roles in skin disease diagnosis, the evaluation of skin cosmetic effect, forensic identification and age identification in sports competition, etc. This paper proposes a new method to evaluate the skin aging objectively and quantitatively by skin texture area. Firstly, the enlarged skin image was acquired. Then, the skin texture image was segmented by using the iterative threshold method, and the skin ridge image was extracted according to the watershed algorithm. Finally, the skin ridge areas of the skin texture were extracted. The experiment data showed that the average areas of skin ridges, of both men and women, had a good correlation with age (the correlation coefficient r of male was 0.938, and the correlation coefficient r of female was 0.922), and skin texture area and age regression curve showed that the skin texture area increased with age. Therefore, it is effective to evaluate skin aging objectively by the new method presented in this paper.
ObjectiveTo construct a cationic microbubble (CMB), and investigate the enhancement of gene transfection efficiency and therapeutic effect of ultrasound-targeted microbubble destruction (UTMD) in vivo with CMB compared to definity MB (DMB).Methods In vitro, the CMB was prepared by the method of thin film hydration. The morphology, size, zeta potential, and gene-carrying capacity of CMB were compared with the DMB. In vivo, the firefly luciferase gene which was used as a reporter gene was targeted transfected into myocardium of 16 rats with CMB and DMB, respectively. The gene transfection efficiency and targeting were observed dynamically. Then, ischemia-reperfusion (I/R) model was performed on 64 rats. The models of 60 rats were successfully confirmed by using ultrasonography at 5 days after I/R. The rats were divided into 3 groups (n=20) randomly. The control group received DMB carrying empty plasmid for transfection; DMB group received DMB carrying AKT plasmid for transfection; and CMB group received CMB carrying AKT plasmid for transfection. The cardiac perfusion, cardiac function, infarct size, and infarct thickness were measured by ultrasonography and histological observations after treatment. In addition, the capillary and arteriolar densities were measured with immunohistochemical staining. The myocyte apoptosis was measured with TUNEL staining. The protein expressions of AKT, phospho-AKT (P-AKT), Survivin, and phospho-BAD (P-BAD) were measured by Western blot.ResultsThe size of CMB was uniformly. The zeta potential of CMB was significantly higher than that of DMB (t=28.680, P=0.000). The CMB bound more plasmid DNA than the DMB (P<0.05). The luciferase activity of myocardium were higher in CMB group than in DMB group bothin vitro and in vivo measurements (P<0.05). There was no significant difference between groups in the ratio of signal intensity in anterior wall to posterior wall, ejection fraction (EF), and fractional shortening (FS) at 5 days after I/R (P>0.05), but the above indexes were significant higher in CMB and DMB groups than in control group at 21 days after I/R (P<0.05). Besides, the above indexes were significant higher in CMB group than in DMB group at 21 days after I/R (P<0.05). The infarct size was the smallest and infarct thickness was the thickest in the CMB group, followed by DMB group, control group at 21 days after I/R. The capillary and arteriolar densities of CMB and DMB groups were significant higher than those of control group at 21 days after I/R (P<0.05). Besides, the capillary and arteriolar densities of CMB group were significant higher than those of DMB group (P<0.05). The apoptotic cells were the most in the control group, followed by DMB group, CMB group at 3 days after gene transfection, showing significant differences between groups (P<0.05). The protein expressions of AKT, P-AKT, Survivin, and P-BAD were significant higher in CMB and DMB groups than those in control group at 3 days after gene transfection (P<0.05). Besides, these protein expressions were significant higher in CMB group than those in DMB group (P<0.05).ConclusionThe DNA-carrying capacity and gene transfection efficiency are elevated by CMB, although its physicochemical property is the same as DMB. When ultrasound-targeted AKT gene transfection is used to treat myocardial I/R injury in rats, delivery of AKT with the CMB can result in higher transfection efficiency and greater cardiac functional improvements compared to the DMB.