PurposeThe monitor of organ microcirculation is significant in the diagnosis and treatment of hemorrhagic shock (HS). We established an HS experimental model and evaluated it by contrast-enhanced ultrasound (CEUS), which aimed to evaluate the value of CEUS and time-intensity curve (TIC) in quantitative analysis of renal cortical microcirculation.Materials and Methods The experimental models of HS were established in 30 healthy New Zealand white rabbits by controlled exsanguinations and were divided into four groups according to the shock grade: normal (100% MAP), mild (70% MAP), moderate (50% MAP) and severe (40% MAP). The right kidneys of the experimental model were examined by CEUS. The corresponding parameters of the TIC such as arrival time (AT), time to peak (TTP), peak intensity (PI) and area under the curve (AUC) were measured with the TIC analysis software package when the region of interest was set in superficial of renal cortex.Results The model of HS were successfully established with 30 healthy New Zealand rabbits. Twenty-seven healthy New Zealand rabbits were alive at the end of the experiment, and three died of severe shock. The TIC rose steeply and reached the peak quickly, and then declined slowly to the baseline, which reflected the transition of microbubble in the region of interest. As the hemorrhagic shock model progressed from normal to mild, PI and AUC gradually decreased and the differences were significant (P<0.05); no significant changes were found in AT and TTP (P>0.05). AT and TTP gradually prolonged compared with normal and mild shock groups, and the differences were significant (P<0.05).Conclusion CEUS and TIC can quickly and accurately assess the renal perfusion changes of acute hemorrhagic shock model of animals in a quantitative way. It can be used as a new noninvasive monitoring tool in quantitative analysis of renal cortical microcirculation.

Purpose To study the effects of different doses of ultrasound contrast agent SonoVue upon contrast-enhanced ultrasound (CEUS) in the kidney of healthy rabbits, and to seek the optimal dose of SonoVue. Materials and Methods CEUS was performed in 10 healthy rabbits with GE LOGIQ-E9 by using 8 different doses of SonoVue (ranging from 0.02 ml/kg to 0.16 ml/kg). The quantitative parameters of the time-intensity curve (TIC) were measured and statistically compared. Results The TICs showed that the peak intensity (PI) and the area under curve (AUC) increased with dose when the doses ranged from 0.02 ml/kg to 0.10 ml/kg (r=0.962 and 0.965, P<0.05); when the dose further increased, AUC had little change but PI decreased reversely. The arrival time (AT) shortened along with the increase of the SonoVue dose (r= - 0.917, P<0.05). The dose had a positive correlation with time to peak (r=0.49, P<0.05). Conclusion The parameters of TIC are influenced intensely by different doses of SonoVue. It is important to realize the relationship between SonoVue doses and its effects upon contrast-enhancement ultrasound in microcirculatory quantification. The dose of 0.10 ml/kg appears to be the optimal dose for CEUS in examining kidney of healthy rabbit.

Objective To explore the effect of reduced alpha - cardiac actin 1(ACTC1)gene expression on the rat embryonic cardiomyocytes H9C2 cell apoptosis and its mechanism. Methods The rat embryonic cardiomyocytes H9C2 cell was cultivated;the rat embryonic cardiomyocytes H9C2 cell was transfected with ACTC1 - small interfering RNA(siRNA),and at 24 h,48 h,72 h after transfection,the cells were collected for extraction and purification of RNA, the real - time quantitative PCR(qPCR)method was used to detect the expression level of ACTC1 gene;and the termi-nal deoxynucleotidyl transferase - mediated dUTP - biotin nick end labeling assay(TUNEL)method was used to ex-plore the effect of reduced ACTC1 gene expression on the rat embryonic cardiomyocytes H9C2 cell apoptosis. Western blot was used to detect the expression of Cyto C,cysteine - containing aspartate - specific proteases(Caspase)- 3, Caspase - 8,Caspase - 9,Bcl - 2 and Bax. Results The expression of ACTC1 mRNA detected by qPCR decreased compared with that of the scramble siRNA group in 24 h,48 h,72 h(0. 80 vs. 1. 00,0. 20 vs. 1. 00,0. 25 vs. 1. 00),and in the ACTC1 - siRNA group decreased significantly at 48 h,72 h,and the difference was statistically significant(t =4. 245,P < 0. 05);TUNEL positive cells rate significantly increased in the ACTC1 - siRNA group(80％)compared with that in the scramble siRNA group(20％),and the difference was statistically significant(P < 0. 05);Western blot also confirmed that the expression of Caspase - 3,Caspase - 9,Cyto C and Bax/ Bcl - 2 were accordingly increased (0. 91 ± 0. 12 vs. 0. 59 ± 0. 01,0. 48 ± 0. 09 vs. 0. 24 ± 0. 03,0. 92 ± 0. 03 vs. 0. 45 ± 0. 01,2. 25 ± 0. 26 vs. 1. 16 ± 0. 12),and the differences were statistically significant(t = 2. 821,7. 336,2. 420,0. 798,all P < 0. 05);but the expre-ssion of Caspase - 8 had no obvious change,and the difference was not statistically significant (P > 0. 05 ). Conclusions Reduced ACTC1 gene expression can induce the rat embryonic cardiomyocytes H9C2 cell apoptosis perhaps mainly through endogenous mitochondrial signal transduction pathways.

Alzheimer′s disease (AD), the most common neurodegenerative disease, is a major challenge in China and all the world. However, the pathogenesis of AD remains unclear, and no disease-modifying therapies are available to prevent or treat the disease. Amyloid-beta (Aβ) and hyperphosphorylated tau protein are key pathological molecules of AD. A series of clinical trials targeting Aβ, tau protein and neuroinflammation have been carried out in the past 20 years, but none of them have been successful in attenuating the cognitive decline so far. This paper discusses the challenges of the current clinical trials of AD and proposes future directions for the research of AD prevention and treatment.