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Neovascularization in plaque is the main driving factor for the formation of vulnerable plaque. It is an effective strategy to alleviate atherosclerosis by intervening neovascularization. Herein, w...

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the modern world, in part due to poor delivery of chemotherapeutics. Sonoporation can be used to enhance the efficacy of standard of care therapies for PDAC. Using xenograft models of PDAC we investigate sonoporation using four ifferent ultrasound contrast agents (UCAs) and two ultrasound regimens to identify the ideal parameters to increase therapeutic efficacy. MIA-PaCa2 xenografts in over 175 immunodeficient mice were treated with gemcitabine and paclitaxel and subjected to low or high power ultrasound (60 and 200 mW/cm(2) respectively) in conjunction with one of four different UCAs. The UCAs investigated were Definity®, SonoVue®, Optison™ or Sonazoid™. Tumor volumes, vascularity, hemoglobin, and oxygenation were measured and compared to controls. High power treatment in conjunction with Sonazoid sonoporation led to significantly smaller tumors when started early (tumors ~50mm(3); p = .0105), while no UCAs significantly increased efficacy in the low power cohort. This trend was also found in larger tumors (~250mm(3)) where all four UCA agents significantly increased therapeutic efficacy in the high power group (p

Myocardial cell injury caused by myocardial ischemia and reperfusion is one of the main causes of the occurrence and development of heart disease. Recent study has shown that inducing mitophagy of cardiomyocytes is a crucial method to alleviate ischemia-reperfusion injury. While, Polo-like kinase 1 (PLK1) can induce the mitophagy of breast cancer cells. Moreover, PLK1 was able to promote the expression of p-AMPK and FUNDC1, which are the protective factors for myocardium. Therefore, the mouse model of ischemia/reperfusion was established and the effect of PLK1 on ischemia reperfusion induced myocardial damage was investigated. The PLK1 was overexpressed in H9c2 cells and rat model of ischemia/reperfusion. Ischemia reperfusion inhibited the expression of PLK1. While overexpression of PLK1 relieved the myocardial infarction and myocardium apoptosis through inducing mitophagy in rats model of ischemia reperfusion. In vitro, the H9c2 cells overexpressing the PLK1 were treated with the hypoxia and reoxygenation and the apoptosis, survival rate and expression of mitophagy-related proteins of H9c2 cells were detected using the flow cytometry, CCK-8 assay and western blotting. The results reveled that overexpression of PLK1 alleviated the hypoxia and reoxygenation induced apoptosis of H9c2 cells and promoted the expression of mitophagy-related proteins. In addition, enhanced PLK1 expression promoted the expression of p-AMPK and FUNDC1 in H9c2 cells. However, the inhibition of FUNDC1 abolished the positive effect of PLK1 on H9c2 cells mentioned above. In conclusion, PLK1 alleviated the ischemia reperfusion induced myocardial damage by inducing the mitophagy in a p-AMPK/FUNDC1 signaling dependent pathway., Graphical Abstract

Background: Previous studies have found that the gender differences have important influences on cardiovascular events, and arterial stiffness is an independent risk factor for cardiovascular events. The arterial pressure volume index (API) is a new indicator for the noninvasive assessment of muscular arterial stiffness. This study was aimed to preliminarily investigate on the gender differences and influencing factors of API from Chinese people, and to discuss the practical application implications of it.Methods: A total of 11118 outpatients were randomly selected and divided into 5 groups according to the age from low to high quintile (Q1: < 37 years old group, Q2: ≥ 37 years old group, Q3: ≥ 51 years old group, Q4: ≥ 61 years old group and Q5: ≥ 69 years old group). The API was obtained by using the cuff oscillation wave for every subject. API≥31 was defined as high API, and body mass index (BMI)≥24 kg/m2 was diagnosed as overweight. The differences of API and high API incidence between male and female subjects in the five groups were compared by Pearson correlation analysis. The risk factors of high API incidence were analyzed by multivariate logistic regression. Results: ①The differences in API and systolic blood pressure(SBP) between the 5 groups were statistically significant, and they increased with age (all PPPPPPConclusion: Among Chinese people of different ages, API differed between male and female; in the whole subjects, the risk of high API is higher for female subjects and overweight subjects.

Carotid webs may cause a frequent recurrent ischemic stroke. Based on the database of patients with transient ischemic attack (TIA), demographics, clinical, and imaging characteristics were compared between the patients with carotid web and without it. Twelve patients with carotid web were younger and more frequent in females than those without it. Both clinical and imaging features determined that the patients with carotid web were prone to TIA due to the pooling of blood with stagnation and the consequent thrombosis. Ultrasonography has big potential for assessment and risk stratification of the carotid web.

Objective: To evaluate the carotid viscoelasticity using ultrasound shear wave dispersion imaging (USWD) and determine its feasibility.Methods: Fifty-three volunteers were recruited and divided into the group1 (≥50 years old) and group 2 (

Intravenous leiomyomatosis (IVL) with intracardiac extension is a rare condition, which the benign tumor invades into the right heart through inferior vena cava. We described the findings of ultrasonography in eight patients with this disease. Transthoracic echocardiography (TTE) can reveal the intracardiac lesion burden and associated compromise. Contrast-enhanced ultrasonography (CEUS) can trace the origin of the lesion and extension. Therefore, combining TTE with CEUS is used to better characterize this complex lesion and plays a crucial role in guidance of surgical decision.

Atherosclerosis (AS) is one of the leading causes of vascular disease, producing high morbidity and mortality in many countries. Autophagy plays an important role when cells are facing serious circumstances, such as oxidative stress induced by Ox-LDL (oxidized low-density lipoprotein). Recent studies have revealed that DEX (dexamethasone acetate) and RAPA (rapamycin) exhibit efficient AS therapeutic ability by protecting endothelial cells and killing foam cells, respectively. Herein, we hypothesize that combining DEX and RAPA together in a specific nanocarrier system can achieve better AS therapy while limiting harmful effects. As a proof of concept, DEX and RAPA coloaded mPEG2k-DSPE calcium phosphate (CaP) nanoparticles (DR-NPs) were prepared by using a biomineralization method. DR-NPs increased HUVEC survival and induced foam cell apoptosis in vitro, which were correlated with autophagy activity. DR-NPs efficiently aggregated at AS plaques in the carotid artery and abdominal artery in ApoE– / – mice 24 h after i.v. injection. Moreover, DR-NPs exhibited excellent plaque regression ability, with smaller necrotic cores and lipid core areas observed after in vivo treatment. Furthermore, the function of vascular endothelial cells was largely promoted, as evidenced by the dramatically decreased expression levels of adhesion factors, such as MMP-2, MMP-9 and ICAM-1. Consequently, DR-NPs can act as an effective AS therapeutic agent and broaden the AS therapeutic approach by inducing autophagy.

Renal transplant (RT) recipients have a high risk of developing cardiovascular diseases. However, the effects of renal transplantation on the development of arteriosclerosis have been controversial. The carotid intima-media thickness (СШТ) and diameter (CD) are important indicators of vascular remodeling and arteriosclerosis. In this study, 31 patients with hemodialysis (HD), 31 RT recipients and 84 age- and gender-matched control subjects were enrolled. Their CIMT and CD were measured by ultrasonic radiofrequency tracking, and the linear regression models and Z test were used to identify the progression of arteriosclerosis and the risk factors. Compared with HD group, RT group had significantly lower CIMT and CD. CIMT was found to be associated with age, body weight, resistance index and diastolic velocity, while CD was associated significantly with age, body weight, pulsatility index, end diastolic velocity and diastolic blood pressure (DBP), respectively. The correlation curves between CIMT and age showed the slopes of curves were decreased successively in control, RT and HD groups, and the curves between CD and age showed the slopes were decreased in order of RT > control > HD groups. It was concluded that CIMT and CD were significantly correlated with age in RT and moderately with age in HD patients. RT could reduce the progress of arteriosclerosis in patients with end-stage renal disease.

Congenital left main coronary atresia (LMCA) is a rare coronary anomaly associated with myocardial ischemia and sudden death. Echocardiography is an important tool for diagnosis of LMCA. The results of echocardiography and relevant clinical signs were retrospectively analyzed in 3 children with LMCA. Echocardiographic examination showed the signs of LMCA: in left coronary sinus no opening of left coronary artery (LCA), retrograded blood flow in LCA, abound blood flow in ventricular wall, and mild widen RCA.

Background This study was aimed to evaluate the feasibility and accuracy of real-time three-dimensional echocardiography (RT-3DE) measurement of left atrial (LA) volume and function in comparison with two-dimensional echocardiography (2DE) measurements in atrial fibrillation (AF) patients. Methods A total of 50 pairs of AF patients and healthy controls were enrolled in this study. Indexed LA end-diastole volume (ILAEDV) and indexed LA end-systolic volume (ILAESV), as well as LA function indices such as segmental LA ejection fraction (LAEF), were assessed using 2DE Simpson’s method and the RT-3DE method. Results The images showed that regional LA volume–time curves and LAEF were disordered in AF patients. ILAEDV and ILAESV were markedly increased and global LAEF was significantly decreased in AF patients compared with those in healthy controls (P

As reliability requirements are increasingly important in both clusters and data centers, RAID-6, which can tolerate any two concurrent disk failures, has been widely used in modern storage systems. However, most existing RAID-6 codes cannot provide satisfied performance on both degraded reads and partial stripe writes, which are important performance metrics in storage systems. To address these problems, in this paper we propose a new RAID-6 MDS erasure code called Short Code, in order to optimize the degraded reads and partial stripe writes. In Short Code, we propose a novel short horizontal parity chain, which assures that all disks contribute to degraded reads while the continuous data elements are more likely to share the same horizontal chain for optimizing degraded reads. On the other hand, Short Code distributes all diagonal parities among disks for optimizing partial stripe writes. The proposed Short Code not only owns the optimal storage efficiency, but also keeps the optimal complexity for both encoding/decoding computations and update operations. The experiments show that Short Code achieves much higher speed on degraded reads and partial stripe writes than other popular RAID-6 codes, and provide acceptable performance on single disk failure recoveries and normal reads. Specifically, compared to RDP code, Short Code provides 6.1 to 26.3 percent higher speed on degraded reads and 36.2 to 80.3 percent higher speed on partial stripe writes with the same number of disks.

Introduction: Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy, but the accurate cause of this syndrome is still unknown. Methods: β-adrenergic agonist isoproterenol (ISO) is used to establish the TTS rats model. TTS rats were treated with or without LY294002 or Rapamycin. The rat cardiomyoblast cell line H9C2 was subjected to infect with constitutively active Akt (myr-Akt) or dominant-negative mutant Akt (dn-Akt) and then, treated with ISO. Cell apoptosis was assessed using the Bax/ Bcl-2 ratio. In addition, reactive oxygen species (ROS) levels were measured using dihydroethidium (DHE). Mitochondrial superoxide generation and membrane potential were assayed by MitoSOX and JC-1 fluorescence intensity. Results: ISO might induce the erratic acute cardiac dysfunction and overexpression of PI3K/AKT/mTOR. Moreover, it also increased the oxidative stress and apoptosis in TTS rats. The Akt inhibitor significantly reversed the cardiac injury effect, which triggered by ISO treatment. In H9C2 cells, the inhibition of Akt provides a protective role against ISO-induced injury by reducing oxidative stress, apoptosis and mitochondrial dysfunction. Conclusion: This study provided new insight into the protective effects of myocardial dysfunction in TTS rats via chronic inhibition of the PI3K/AKT/mTOR expression, which could reduce mitochondrial ROS and oxidative stress-induced apoptosis. PI3K/AKT/mTOR inhibitor could be a therapeutic target to treat cardiovascular dysfunction induced by stress cardiomyopathy.

Background: This study evaluates carotid vulnerable plaques using contrast-enhanced ultrasound (CEUS) and explores the relationship between vulnerable plaques and leukocytes.Methods: Sixty-two symptomatic and 54 asymptomatic patients underwent CEUS. The images were analyzed using time-intensity and fitting curves, and peak (PTIC), mean (MTIC), peak (PFC), sharpness (SFC), and area under the curve (AUCFC) were obtained. The relations between CEUS parameters and leukocytes were analyzed.Results: In the symptomatic group, total leukocytes and neutrophils were higher, while lymphocyte was decreased; PTIC, MTIC, PFC, SFC,, and AUCFC were significantly higher; MTIC and AUCFC were negatively correlated with lymphocytes, and MTIC was positively correlated with neutrophils. Classification and regression tree analysis showed that MTIC at a cutoff of 20.8 and AUCFC at a cutoff of 8.8 resulted in a predictive of acute cerebral infarction, accuracy of 84.3%, sensitivity of 87.1%, and specificity of 81.5%.Conclusions: The variation in the perivascular leucocyte is significantly related to intraplaque inflammatory activities, CEUS is a feasible monitor of intraplaque neovascularization, so CEUS combined with perivascular leucocyte could be helpful as a warning for vulnerable plaques.

This study evaluated sonoporation in a xenograft model of pancreatic ductal adenocarcinoma (PDAC) using 4 different ultrasound contrast agents (UCAs) to select the optimal UCA for augmenting chemotherapy treatment. Athymic, nude, female mice (n = 120) were inocluated with MIA PaCa-2 cells in the right flank, and randomized into 2 control groups (vehicle or standard of care chemotherapy with paclitaxel and gemcitabine), and 8 treatment groups. These consisted of chemotherapy and one of 4 UCAs: Definity® (Lantheus Medical Imaging, N Billerica, MA, USA), Lumason® (Bracco, Milan, Italy), Optison™ (GE Healthcare, Princeton, NJ, USA) or Sonazoid™ (GE Healthcare, Oslo, Norway) scanned in a high or a low acoustic power cohort (ISPTA of 200 or 60 mW/cm2, respectively). Groups of 10 animals were treated once a week for 3 weeks with chemotherapy followed by a 10 minute infusion of one of the UCAs through a tail vein. Hemoglobin and oxygenation measurements were obtained weekly (at baseline, during treatment and 1 week post treatment) in subgroups (3 mice from each group) using 3D photoacoustic imaging on a Vevo 2100 LAZR scanner (Fujifilm Visualsonics, Toronto, Canada). The remaining mice were followed for tumor volume growth and survival. Groups were compared with two-way, repeated measures ANOVAs. Tumor volumes from the 4 treatment groups in the high acoustic power cohort were smaller than those of the group receiving chemotherapy alone (p

To study the differences of cardiovascular system between men and women in response to exercise stress.Forty healthy youth were tested according to Bruce protocol of exercise stress. They were detected by ultrasonography during the rest, peak exercise, and recovery stages, respectively. The left ventricular diastolic elastance (Ed), effective arterial elastance (Ea), left ventricular end-systolic elatance (Ees), ventricular-vascular coupling index (VVI), and total stiffness index (TSI) were measured and calculated according to the formulas. The results of all stages were compared according to genders.All stages, the Ed, TSI, and VVI of women were higher than those of men, but the Ees was lower than that of men (all P0.05); there was no significant difference in Ea between men and women. The Ed, Ees, Ea, and TSI were closely related with left ventricular oxygen consumption and heart function, and women showed more closely. Before and after exercise, the changes were different in Ed, Ees, Ea, TSI, and VVI (all P0.05), and VVI changed least.Before and after exercise, the ventricular stiffness matched well with arterial stiffness and maintained within a narrow range. For women, the tolerance of exercise was lower than that of men.

Inflammatory activity plays a central role in the development of carotid rupture-vulnerable atherosclerotic plaques, which is one of the major contributors to acute ischemic stroke. Our objective was to characterize carotid intraplaque neovascularizations (INP) using contrast-enhanced ultrasound (CEUS) and evaluate plaque burden through exploring the relationship between INP and cell count of peripheral leukocytes. Sixty-two patients with large artery atherosclerosis (LAA) were enrolled in this study. CEUS was performed to characterize the carotid artery plaques. The correlations between the CEUS imaging features of carotid plaques and leukocyte counts were investigated. The results showed that the characteristic parameters derived from CEUS, including peak of time-intensity curve (TIC-P), mean of time-intensity curve (TIC-M), peak (FC-P), sharpness (FC-S) and area under the curve (FC-AUC) compared with the control group, were all increased in the stroke group. TIC-P, TIC-M and FC-P were negatively related to lymphocytes, respectively. FC-S and FC-AUC were positively correlated with neutrophils, respectively. Our study indicated carotid INP was closely related to the peripheral leukocytes count. CEUS may serve as a useful tool to predict vulnerability of plaque.

Figure S1. Repeatability was analyzed by Bland-Altman Plots in intergroup. Bland-Altman analysis showed a consistent trend in the difference value and the mean value of CIMT by repeated measurement. Figure S2. Repeatability was analyzed by linear correlation analysis in intergroup. The results showed that intergroup comparison had a high degree of consistency. Figure S3. Repeatability was analyzed by Bland-Altman Plots in intergroup. Bland-Altman analysis showed a consistent trend in the difference value and the mean value of PWV by repeated measurement. Figure S4. Repeatability was analyzed by linear correlation analysis in intergroup. The results showed that intergroup comparison had a high degree of consistency. (DOCX 104Â kb)

The cardiovascular interaction responses to exercise testing have been widely investigated in patients with cardio-cerebrovascular disease. However, little is known regarding cardiovascular stiffness in response to exercise in healthy adults. We therefore sought to study alterations in

Aims: This study’s aim is to present the specific ultrasonography (US) findings of a series of urachus anomalies. Material and methods: Seven patients with suspected urachal anomalies underwent US scanning initially prior to the surgery and the features of images were reviewed respectively. The clinical data and pathologic results were collected also. Results: US successfully diagnosed urachal anomalies in 5 patients (5/7, 71.4%) and failed to diagnose in 2 patients (2/7, 28.6%). Patent urachus showed a tubule between the umbilicus and bladder; urachal sinus was a blind focal dilatation at the umbilical end, while vesicourachal diverticulum was an outpouching at the vesical end and urachal cyst was identified as an anechoic structure along the urachus. Non-enhancement in the base and centre was the distinct features of urachus carcinoma by contrastenhanced ultrasonography (CEUS). Using a high frequency probe and CEUS the diagnostic ability of US may be improved. Conclusion: US showed good diagnostic ability in urachal anomalies and combined with CEUS could improve the differential diagnosis.

Aim: Arterial wall elasticity including the circumferential and longitudinal modulus is a measure of sub-clinical cardiovascular disease; the circumferential modulus is increased in acute ischemic stroke (AIS). There are still no reports of non-invasive measurement of longitudinal elastic modulus of arterial wall and its prospect of clinical application. In this study, the longitudinal elastic modulus of the arterial wall was assessed using real-time shear wave elastography in patients with AIS. The technique’s feasibility and its related factors were studied initially. Materials and methods: In this study 179 patients with AIS and 168 age- and sex-matched controls were examined. The pulse wave velocity (PWV) of the bilateral carotid arteries was measured using radio frequency ultrasound technology. The 20 areas of superficial walls of bilateral carotid artery were analyzed by real-time shear wave elastography (SWE), and the average values of longitudinal average elastic modulus (ME mean ), maximum elastic modulus (ME max ), minimum elastic modulus (ME min ), and elastic modulus standard deviation (ME SD ) were measured. Results: The PWV, ME mean , ME max and ME SD of the carotid artery in patients with AIS were greater than those in the control group. Age, systolic blood pressure, PWV, and low-density lipoprotein were positively related to ME mean and ME max ( r =0.221and r =0.248, r =0.174 and r=0.176, r =0.776 and r=0.716, r =0.173 and r=0.200, p

Many RAID-6 codes have been proposed in the literature, but each has its limitations. Horizontal code has the ability to adapt to the arbitrary size of a disk array but its high computational complexity is a major shortcoming. In contrast, the computational complexity of vertical code (e.g. X-code) often achieves the theoretical optimality, but vertical code is limited to using a prime number as the size of the disk array In this article, we propose a novel efficient RAID-6 code for arbitrary size of disk array: generalized X-code. We move the redundant elements along their calculation diagonals in X-code onto two specific disks and change two data elements into redundant elements in order to realize our new code. The generalized X-code achieves optimal encoding and updating complexity and low decoding complexity; in addition, it has the ability to adapt to arbitrary size of disk array. Furthermore, we also provide a method for generalizing horizontal code to achieve optimal encoding and updating complexity while keeping the code's original ability to adapt to arbitrary size of disk array.

Carotid arterial dissection is an important cause of stroke in young and middle-aged patients. Ultrasound (and particularly contrast enhanced ultrasonography) is an important approach in patients with sudden onset of stroke combined with renal failure who are not suitable for angiography. In this report we describe the ultrasound features of carotid arterial dissection and discuss its utility.