1.Experimental study of combining ultrasound targeted microbubble destruction with nuclear localization signal peptide to enhance gene transfection in treatment of canines myocardial infarction
Jingjing CUI ; Qing ZHOU ; Sheng CAO ; Qing DENG ; Bo HU ; Yijia WANG
Chinese Journal of Ultrasonography 2017;26(2):159-164
Objective To improve the canines myocardial infarction curative effect by using ultrasound targeted microbubble destruction (UTMD) combining with nuclear localization signal(NLS) peptide to increase hAng-1 gene transfection efficiency.Methods Forty-six canines were randomly divided into 4 groups (n=10 in each group) after the models of myocardial infarction were prepared.Group A were untreated control;Group B were transfected with hAng-1;Group C were transfected with UTMD+hAng-1;Group D were transfected with UTMD+NLS nuclear localization signal+hAng-1.The therapeutic agents were intravenously injected at one week after myocardial infarction in each group,and the ultrasound were irradiated at the precardium in group C and D.①Echocardiography was used before and at one week after myocardial infarction and 28 days after gene transfection.Two-dimensional echocardiography was used to detect cardiac function,the left ventricular ejection fraction,the left ventricular wall motion and the myocardial contrast echocardiography were used to detect myocardial perfusion of all canines in the four groups.②On twenty-eight days after gene transfection,mRNA and Western Blot were used to detect the expression of hAng-1.Immunohistochemistry was used to detect capillary density of peri-infarct area and microvessel density (MVD).Masson′s trichromatic staining and gross specimen were used to evaluate the degree and the area of myocardial fibrosis.The gene transfection efficiency and the curative effect of all the four groups were evaluated and compared.Results ①Before myocardial infarction,in four groups canine ventricular wall motion and cardiac function were normal,and myocardial filling defect was not showed by myocardial contrast echocardiography.At one week after myocardial infarction,the left ventricular anterior and interval walls motion and the left ventricular ejection fraction in the four groups were significantly decreased.Myocardial contrast echocardiography showed anterior and interval walls myocardial filling defect.There was no significant difference among the four groups(P>0.05);On 28 days after gene transfection the left ventricular ejection fraction in the four group were increased in an order of group A,B,C,D,there was significant difference when comparing group C and D with other groups separately(P<0.05).Myocardial contrast echocardiography showed much contrast filling in the infarction and surrounding area in group D,a little contrast filling in group C and filling defect in group A and group B,there was significant difference when comparing group C and D with other groups separately(P<0.05).②RT-PCR and Western Blot showed the hAng-1 mRNA and protein expression in group D were higher than those in the other group.There was significant difference when comparing group C and group D with other groups separately(P<0.05).③Immunofluorescence showed the capillary densities were(4.7±1.6)/mm2,(11.2±2.8)/mm2,(70.0±6.4)/mm2 and (85.3±7.0)/mm2 in group A,group B,group C and group D.The differences were statistically significant compared group C and group D with other groups (P<0.05).④Masson′s trichromatic staining and cardiac gross specimen showed that the degree and area of myocardial fibrosis were gradually reduced in an order of group A,B,C,D.Conclusions UTMD and NLS peptide could effectively transfect hAng-1 gene and it provided a novel strategy of gene treatment for ischemic heart disease.
2.Evaluation of fluid field of left ventricle outflow tract in hypertrophic obstructive cardiomyopathy with fluid models based on three-dimensional echocardiography with inverted grey values
Hongning SONG ; Yijia WANG ; Tuantuan TAN ; Sheng CAO ; Qing ZHOU ; Ruiqiang GUO
Chinese Journal of Ultrasonography 2021;30(11):961-967
Objective:To explore the effect of systolic anterior motion (SAM) of mitral valves on the morphology and function of left ventricular outflow tract (LVOT) in patients with hypertrophic obstructive cardiomyopathy (HOCM) using computer fluid dynamics based on three-dimensional echocardiography with inverted grey values.Methods:A total of 40 patients with hypertrophic cardiomyopathy were divided into SAM group (24 cases) and non SAM group (16 cases) in Renmin Hospital of Wuhan University from April 2016 to October 2019. Two dimensional and three-dimensional echocardiographic data of the patients were collected. The LVOT morphological model was constructed based on the post-processing of three-dimensional echocardiography data, and the LVOT flow field model was constructed based on the time-volume curve of left ventricle. LVOT peak velocity was obtained to assess the agreement with echocardiography measurements. Area of LVOT, average velocity, flow rate and iso-surface area of vortex of different levels were obtained and compared between the two groups.Results:There was a good correlation between cardiac fluid model and echocardiographic measurement ( r=0.943, P<0.01). The Bland-Altman consistency interval was -75.0-111.3, and 92.5% of the points were within the consistency limit. Compared with non-SAM group patients, the peak velocity of LVOT increased, the area of LVOT decreased, the flow rate decreased and the area of vortex increased in SAM patients (all P<0.01). In the SAM group, in 16 patients the double orifice LVOT was observed due to the contact between mitral valve and septum, in 1 patient the single orifice LVOT structure was observed with contact between mitral value and septum, and in 7 patients, single orifice LVOT without contact between mitral value and septum. In SAM patients, compared with single orifice LVOT, patients with double orifice LVOT were observed with higher LVOT velocity, smaller LVOT area and higher vortex area with high level(all P<0.05). Conclusions:Accurate fluid models can be obtained using three-dimensional echocardiography with inverted grey values. In SAM patients, contact between mitral valve and septum leads to the formation of double orifice structure and the increase of vortex level in LVOT.
3.Influencing factors of death in intensive care unit patients with acute respiratory distress syndrome combined with acute kidney injury after continuous renal replacement therapy
Yajun HUANG ; Yue GU ; Wenwen ZHANG ; Mei GAO ; Yijia SHENG ; Yingying REN ; Lei YAN ; Fengmin SHAO
Chinese Journal of Nephrology 2021;37(9):723-729
Objective:To analyze the influencing factors of death in patients with acute respiratory distress syndrome (ARDS) combined with acute kidney injury (AKI) in intensive care unit (ICU) after continuous renal replacement therapy (CRRT).Methods:The demographic and clinical data of ICU patients with ARDS combined with AKI after CRRT at Henan Provincial People's Hospital from January 1, 2018 to December 31, 2018 were collected. According to the final treatment results of this hospitalization, the patients were divided into death group and survival group. Survival was defined as the improved patient's condition and hospital discharge. Death was defined as the patient's death during the ICU hospitalization or confirmed death after abandoning treatment and automatically being discharged from the hospital in the follow-up. The basic clinical characteristics and CRRT status between the two groups were compared. Multivariate logistic regression method was used to analyze the influencing factors of death in patients.Results:A total of 132 patients were enrolled, of which 90 patients (68.2%) died, with 84 males (63.6%) and median age of 59(45, 73) years. Compared with the survival group, the death group had higher age, proportion of malignant tumors, sequential organ failure assessment (SOFA) score, number of organ dysfunction and proportion of positive balance of fluid accumulation at 72 hours, longer time from entering ICU to CRRT, and lower mean arterial pressure (minimum value) and oxygenation index (all P<0.05). Multivariate logistic regression analysis results showed that the age≥60 years old ( OR=4.382, 95% CI 1.543-12.440, P=0.006), large number of organ dysfunction ( OR=1.863, 95% CI 1.109-3.130, P=0.019), high SOFA score ( OR=1.231, 95% CI 1.067-1.420, P=0.004) and long time from ICU admission to CRRT ( OR=1.224, 95% CI 1.033~1.451, P=0.020) were independent influencing factors of death in patients with ARDS combined with AKI after CRRT, and high oxygenation index ( OR=0.992, 95% CI 0.986-0.998, P=0.010) was an independent protective factor for patients' prognosis. Conclusions:The mortality of patients with ARDS combined with AKI after CRRT is still high. The age≥60 years old, large number of organ dysfunction, high SOFA score and long time from ICU admission to CRRT are independent influencing factors for death, and high oxygenation index is an independent protective factor for prognosis in patients with ARDS combined with AKI after CRRT.