Aortic stiffness evaluated by echocardiography in female patients with Takayasu's arteritis.

OBJECTIVES: The aim of this study was to evaluate the aortic stiffness (AS) in young female patients with Takayasu's arteritis (TAK) and comparable controls by measuring carotid-femoral PWV (PWVcf) using echocardiography with pulse wave Doppler. The clinical feasibility and reproducibility of this echocardiographic method were also investigated. METHODS: Twenty-five TAK female patients (mean age 28.3±6.2 years) and 25 strictly matched healthy controls were included according to rigorous inclusion and exclusion criteria. The PWVcf of all subjects were measured by echocardiography based on the principle that PWVcf could be calculated by pulse wave spreading distance divided by the transmit time. Reproducibility of the echocardiographic measured PWVcf were performed randomly in 15 TAK patients and 15 healthy controls. RESULTS: The patients with TAK had a higher PWVcf value measured by echocardiography, compared with healthy controls (8.37±2.23 vs. 6.46±1.15 m/s; p<0.001). The echocardiographic measured PWVcf was significantly dependent on the TAK (p=0.003), age (p=0.032) and pulse pressure (p=0.025). PWVcf did not correlate with the echocardiographic measured cardiac systolic and diastolic parameters and the laboratory variables in TAK patients (p>0.05 for all). The intra- and inter-observer coefficients of variation were low and the Bland-Altman plots indicated a satisfactory reproducibility. CONCLUSIONS: Our results indicated that AS in female patients with TAK is increased, which may predict a higher cardiovascular risk. This manifestation is prior to the impairment of cardiac diastolic function. This elevated AS can be detected by echocardiographic measured PWVcf with a good reproducibility.

N-Acetyl Cysteine improves the diabetic cardiac function: possible role of fibrosis inhibition.

BACKGROUND: Diabetic cardiomyopathy is one of the leading causes of death in diabetes mellitus (DM) patients. This study aimed to explore the therapeutic implication of N-acetyl-L-cysteine (NAC, an antioxidant and glutathione precursor) and the possible underlying mechanism. METHODS: Thirty five 12-week-old male C57BL/6 mice were included. Twenty-five diabetic mice were induced by intraperitoneal injection of streptozocin (STZ, 150 mg/kg, Sigma-Aldrich) dissolved in a mix of citrate buffer after overnight fast. Mice with a blood glucose level above 13.5 mmol/L were considered diabetic. As a non-DM (diabetic) control, mice were injected with equal volume of citrate buffer. The 25 diabetic mice were divided into 5 groups with 5 animals in each group: including DM (diabetes without NAC treatment), and 4 different NAC treatment groups, namely NAC1, NAC3, NAC5 and NAC7, with the number defining the start time point of NAC treatment. In the 10 non-DM mice, mice were either untreated (Ctrl) or treated with NAC for 5 weeks (NAC only). Echocardiography was performed 12 weeks after STZ injection. Heart tissue were collected after echocardiography for Hematoxylin Eosin (HE) and Trichrome staining and ROS staining. Cardiac fibroblast cells were isolated, cultured and treated with high glucose plus NAC or the vehicle. qPCR analysis and CCK-8 assay were performed to observe fibrotic gene expression and cell proliferation. RESULTS: We found that both cardiac systolic function and diastolic function were impaired, coupled with excessive reactive oxygen stress and cardiac fibrosis 12 weeks after STZ induction. NAC significantly reduced ROS generation and fibrosis, together with improved cardiac systolic function and diastolic function. Strikingly, NAC1 treatment, which had the earlier and longer treatment, produced significant improvement of cardiac function and less fibrosis. In the cardiac fibroblasts, NAC blocked cardiac fibroblast proliferation and collagen synthesis induced by hyperglycemia. CONCLUSIONS: Our study indicates that NAC treatment in diabetes effectively protects from diabetic cardiomyopathy, possibly through inhibiting the ROS production and fibrosis, which warrants further clarification.

Carotid Arterial Stiffness in Patients with Congenital Heart Disease-Related Pulmonary Hypertension Assessed with Radio Frequency Data Technique.

BACKGROUND: It has been well known that pulmonary hypertension (PH) caused by congenital heart disease (CHD) leads to reduced flexibility of the small pulmonary arteries, due to hemodynamic changes in the pulmonary circulation and alterations of the vasoactive profile. However, whether CHD-related PH affects the elasticity of the systemic arteries, such as the common carotid artery (CCA), has not been fully investigated. The purpose of this study was to explore the CCA stiffness in patients with CHD-related PH using the radio frequency data technique. METHODS: Forty patients with CHD were included. They were divided into PH and non-PH (NPH) groups by the right heart catheter-determined or regurgitation velocity-determined mean pulmonary arterial pressure (mPAP). MyLabTwice (Esaote, Genoa, Italy) ultrasound machine equipped with automatic quality intima-media thickness (QIMT) and quality arterial stiffness (QAS) capabilities was used to measure the left common carotid arterial (CCA) intima-media thickness and arterial stiffness parameters. RESULTS: The results have shown that the left CCA internal diameter, pulse wave velocity, arterial wall tension, and local diastolic pressure were increased in the CHD-related PH group compared with the CHD-related NPH group (all P < 0.05). The left CCA internal diameter negatively and significantly correlated with the mean PAP. CONCLUSIONS: Common carotid artery diameter and stiffness increase in patients with CHD-related pulmonary hypertension. QIMT and QAS ultrasound techniques may provide a comprehensive assessment of the CCA remodeling.

Evaluation of carotid artery elasticity changes in patients with type 2 diabetes.

BACKGROUND: Type 2 diabetes is one of the most common causes of cardiovascular disease as it causes arterial stiffness changes. The purpose of this study is to characterize, in vivo, carotid arterial structural and functional changes by applying radio frequency and X-strain ultrasound techniques. METHODS: Ninety-one subjects were assigned into two groups; a diabetes group and a control group. Structural and functional changes in the common carotid arterial wall were investigated by quality intima-media thickness (QIMT), quality arterial stiffness (QAS), and X-strain analysis with a Mylab Twice ultrasound instrument. The relationships among variables between the two groups were analyzed in this study. RESULTS: There was no significant difference in carotid IMT (626.5 ± 169.1 µm vs. 568.5 ± 122.6 µm, P = 0.1506) between two groups. Pulse wave velocity (PWV) and stiffness index (ß) were remarkably greater (8.388 ± 3.254 m/s vs. 7.269 ± 1.332 m/s; 12.51 ± 14.16 vs.9.279 ± 2.871), while compliance coefficient (CC) decreased significantly in the diabetes group (0.802 ± 0.3094 mm2/Kpa vs. 0.968 ± 0.3992 mm2/Kpa) (P < 0.05). The displacement difference of radial (RD-D), longitudinal (LD-D) and rotation (ROT-D) directions were significantly different between two groups' comparison (P = 0.0212, P = 0.0235 and P = 0.0072, respectively). The time of circumferential peak strain difference (CS-DT) and the time of radial peak strain rate (RSR-T) were found to be significantly different between the two groups (341.9 ± 77.56 ms vs. 369.0 ± 78.26 ms, P = 0.0494; 142.7 ± 22.43 ms vs. 136.2 ± 30.70 ms, P = 0.0474). CS-TD and RSR-T were also found to be positively correlated with CC value (r = 0.3908, P < 0.005 and r = 0.3027, P = 0.0326, respectively). Finally, PWV was negatively correlated with CC with (r = -0.6177, P < 0.001). CONCLUSIONS: In type 2 diabetes, the functional changes in CCA can be identified using the methods presented in this article earlier than the structural changes. Arterial stiffness values provided by QAS and X-strain analysis can be used as indicators of CCA functional lesions in patients with type 2 diabetes.

Ultrasound study of carotid and cardiac remodeling and cardiac-arterial coupling in normal pregnancy and preeclampsia: a case control study.

BACKGROUND: Cardiovascular adaptions, such as cardiac and uterine spiral arterial remodeling, and aortic arterial stiffening during pregnancy have been extensively investigated, while the interactions between the elastic artery and the left ventricle are poorly understood. This study was to evaluate the cardiac-arterial coupling in both normal pregnancy and preeclampsia using ultrasound techniques. METHODS: Twenty-three preeclamptic women with no antihypertensive treatment prior to admission, and 40 age- (27.2 ± 3.0 y vs. 29.1 ± 5.7 y, p = 0.0805) and gestational week- (35.6 ± 3.4 wk vs. 34.8 ± 3.6 wk, p = 0.3573) matched normotensive pregnant women were included. All women signed informed consent. All were nulliparas, had singleton pregnancies, and had no other risk factors for arterial stiffening. Carotid and cardiac ultrasound was performed using a MylabTwice ultrasound unit (Esaote, Italy). Cardiac and carotid remodeling and their associations were analyzed. Left ventriculo-carotid coupling was characterized by the ratio between the arterial elastance (Ea) and the left ventricular systolic elastance (Ees). Follow-up study was performed 16-20 months after parturition. RESULTS: Left ventricular and carotid arterial remodeling was seen more frequently in preeclamptic women than in normal pregnant controls (96% vs. 40%, 82% vs. 48%, both p < 0.0001). The relative carotid arterial wall thickness showed no significant difference between the two groups. However, the carotid cross-sectional area, a surrogate for carotid arterial mass, was significantly greater in preeclampsia than that in normal controls (11.23 ± 0.17 mm2 vs. 8.58 ± 1.88 mm2, p < 0.00001). Carotid arterial stiffness and intima-media thickness correlated significantly with cardiac diastolic function parameters and blood pressures (p < 0.05). Both Ea and Ees were significantly greater in preeclampsia, compared with values in normal pregnant controls (Ea: 2.41 ± 0.57 mmHg/ml vs. 1.98 ± 0.46 mmHg/ml, p = 0.0005; Ees: 11.68 ± 9.51 m/s2 vs. 6.91 ± 6.13 m/s2, p = 0.002). However, there was no significant difference in the left ventriculo-carotid coupling index, Ea/Ees, between the two groups. Carotid remodeling persisted in both preeclamptic women and normal pregnant controls 16-20 months after parturition. CONCLUSIONS: Significant cardiac and carotid remodeling and similar left ventriculo-carotid coupling were observed in both preeclampsia and normal pregnancy. Carotid remodeling may persist postpartum. Further studies with larger populations are needed to confirm these findings.

Normal and shear strains of the left ventricle in healthy human subjects measured by two-dimensional speckle tracking echocardiography.

BACKGROUND: Animal studies have shown that shear deformation of myocardial sheets in transmural planes of left ventricular (LV) wall is an important mechanism for systolic wall thickening, and normal and shear strains of the LV free wall differ from those of the interventricular septum (IVS). We sought to test whether these also hold for human hearts. METHODS: Thirty healthy volunteers (male 23 and female 7, aged 34 ± 6 years) from Outpatient Department of the University of Tokyo Hospital were included. Echocardiographic images were obtained in the left decubitus position using a commercially available system (Aloka SSD-6500, Japan) equipped with a 3.5-MHz transducer. The ECG was recorded simultaneously. The peak systolic radial normal strain (length change), shear strain (angle change) and time to peak systolic radial normal strain were obtained non-invasively by two-dimensional speckle tracking echocardiography. RESULTS: The peak systolic radial normal strain in both IVS and LV posterior wall (LVPW) showed a trend to increase progressively from the apical level to the basal level, especially at short axis views, and the peak systolic radial normal strain of LVPW was significantly greater than that of IVS at all three levels. The time to peak systolic radial normal strain was the shortest at the basal IVS, and increased progressively from the base to the apical IVS. It gradually increased from the apical to the basal LVPW in sequence, especially at short axis views. The peak of radial normal strain of LVPW occurred much later than the peak of IVS at all three levels. For IVS, the shear deformation was clockwise at basal level, and counterclockwise at mid and apical levels in LV long-axis view. For LVPW, the shear deformations were all counterclockwise in LV long-axis view and increased slightly from base to the apex. LVPW showed larger shear strains than IVS at all three levels. Bland-Altman analysis shows very good agreement between measurements taken by the same observer and by two independent observers. CONCLUSION: "Myocardial sheets" theory also holds true for intact human LV. Moreover, dyssynchrony exists even in healthy human subjects, which should be considered when evaluating the diseased hearts.

Middle cerebral arterial flow changes on transcranial color and spectral Doppler sonography in patients with increased intracranial pressure.

OBJECTIVES: Intracranial pressure usually increases after severe brain injury. However, a method for noninvasive evaluation of intracranial pressure is still lacking. The purpose of this study was to explore the potential role of transcranial color Doppler sonography in assessing intracranial pressure by observing the middle cerebral artery blood flow parameters in patients with increased intracranial pressure of varying etiology. METHODS: The hemodynamic changes in the middle cerebral artery in patients with varying degrees of increased intracranial pressure were investigated by transcranial color Doppler sonography in 93 patients who had emergency surgery for brain injury. RESULTS: Middle cerebral artery Doppler flow spectra changed regularly as intracranial pressure increased. The pulsatility index (PI) and resistive index (RI) had a significantly positive correlation with intracranial pressure (r = 0.90 and 0.89, respectively; P< .001), whereas the middle cerebral artery diastolic velocity showed a significant negative correlation with intracranial pressure (r = -0.52; P< .01). A receiver operating characteristic curve showed that the RI and PI cutoff values were 0.705 and 1.335, respectively, for predicting increased intracranial pressure, with sensitivity of 0.885 and specificity of 0.970. CONCLUSIONS: In addition to the PI and RI, middle cerebral artery diastolic flow velocity measurement by transcranial color Doppler sonography may also be a useful variable for evaluating intracranial pressure in patients with acute brain injury.

Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

Maternal carotid remodeling and increased carotid arterial stiffness in normal late-gestational pregnancy as assessed by radio-frequency ultrasound technique.

BACKGROUND: The adaption of elastic arteries to transient increase in hemodynamic load in normal pregnancy (NP) remains controversial. The purpose of this study was to investigate the NP carotid remodeling and regional arterial stiffness before and after parturition. METHODS: Fifty-one NP women and 30 age-matched non-pregnant women were included. All women underwent right common carotid artery (RCCA) measurements with MylabTwice ultrasound instrument (Esaote, Italy). Carotid intima-medial thickness (IMT), pulse wave velocity (PWV, m/s), distensibility coefficient (DC, 1/KPa), α, ß, augmentation index (AIx, %) and carotid arterial pressure were obtained by the newly developed ultrasound vascular wall tracking methods: automatic QAS (Quality Arterial Stiffness) and QIMT (Quality Intima-Medial Thickness) Follow up study was performed. RESULTS: Compared to the non-pregnant controls, the arterial pressures were significantly increased and RCCA diameter was significantly enlarged in late gestational NP women. Twenty months after parturition, carotid diameter, DC, AIx, PWV and arterial wall tension were significantly decreased and had no significant difference with those in non-pregnant controls. CONCLUSIONS: Carotid arterial remodeling and stiffening could be seen in the normal pregnant women, which seems to be a physiological adaption and could be recovered post partum. QIMT and QAS together could provide a comprehensive assessment of the maternal carotid arterial changes during pregnancy.

Computational protein design to reengineer stromal cell-derived factor-1α generates an effective and translatable angiogenic polypeptide analog.

BACKGROUND: Experimentally, exogenous administration of recombinant stromal cell-derived factor-1α (SDF) enhances neovasculogenesis and cardiac function after myocardial infarction. Smaller analogs of SDF may provide translational advantages including enhanced stability and function, ease of synthesis, lower cost, and potential modulated delivery via engineered biomaterials. In this study, computational protein design was used to create a more efficient evolution of the native SDF protein. METHODS AND RESULTS: Protein structure modeling was used to engineer an SDF polypeptide analog (engineered SDF analog [ESA]) that splices the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a diproline segment designed to limit the conformational flexibility of the peptide backbone and retain the relative orientation of these segments observed in the native structure of SDF. Endothelial progenitor cells (EPCs) in ESA gradient, assayed by Boyden chamber, showed significantly increased migration compared with both SDF and control gradients. EPC receptor activation was evaluated by quantification of phosphorylated AKT, and cells treated with ESA yielded significantly greater phosphorylated AKT levels than SDF and control cells. Angiogenic growth factor assays revealed a distinct increase in angiopoietin-1 expression in the ESA- and SDF-treated hearts. In addition, CD-1 mice (n=30) underwent ligation of the left anterior descending coronary artery and peri-infarct intramyocardial injection of ESA, SDF-1α, or saline. At 2 weeks, echocardiography demonstrated a significant gain in ejection fraction, cardiac output, stroke volume, and fractional area change in mice treated with ESA compared with controls. CONCLUSIONS: Compared with native SDF, a novel engineered SDF polypeptide analog (ESA) more efficiently induces EPC migration and improves post-myocardial infarction cardiac function and thus offers a more clinically translatable neovasculogenic therapy.

A prospective experimental study of liver fibrosis with ultrasound and its correlation with hepatic reserve function and hemodynamics.

BACKGROUND: Progressive hepatic fibrosis is the eventual cause of liver cirrhosis. Doppler ultrasound has been used to detect hemodynamic changes that are known to be present during the pre-cirrhotic stages of hepatic fibrogenesis. However, the relationship between the Doppler ultrasound parameters and the impairment of the liver function has not been fully investigated. The purpose of this study was to explore the hepatic function reserve and its relationship with the hepatic hemodynamics in a rabbit model of liver fibrosis using Doppler ultrasound. METHODS: A prospective study was performed. Sixty healthy New Zealand rabbits were included in this study. Eleven of them served as controls and were normally fed and provided with water drink; the rest of 49 rabbits that served as fibrosis group were normally fed but provided with 1.2 g/L of thioacetamide to create liver fibrosis model. Doppler measurements were performed in the portal trunk, proper hepatic artery and proper splenic artery. The hepatic circulation index (HCI) was calculated. Hepatic function reverse was evaluated by measuring the indocyanine green clearance and retention rate at 15 min (ICG R15) test. Portal venous pressure (PVP) was measured using the portal vein punctuation equipment. RESULTS: HCI was significantly decreased and PVP increased in the advanced fibrotic stage (F4) compared to mild and moderate fibrotic stage (F1-3), respectively (p<0.05). PVP and ICG R15 in the fibrotic group were significantly higher than that in the control group (ICG: 0.209±0.086 vs. 0.093±0.023, p<0.01). Within the fibrotic groups, PVP was higher in advanced fibrotic stage (F4) than those in mild (F1-2) or moderate (F3) fibrotic stages (p<0.05). Both HCI and PVP correlated well with ICG R15 (r = -0.890, and r = 0.780, p <0.01). CONCLUSIONS: Hepatic function reserve closely relates to the hepatic hemodynamics in the rabbit model of liver fibrosis. Doppler Ultrasound could be reliably used to assess the hepatic function reserve and hemodynamic changes in different stages of liver fibrosis.

Double-chambered left ventricle in echocardiography.

In this article, we describe a double-chambered left ventricle (LV) in a 37-year-old man. Its accessory chamber attached to the inferior and posterior wall of LV, and had normal systolic contraction without any regional wall motion abnormality. A double-chambered LV was suspected on echocardiography and confirmed by cardiac computed tomography scanning and cardiac magnet resonance imaging. Our aim is to accentuate the value of echocardiography in this rare anomaly

Value of the echocardiographic suprasternal view for diagnosis of patent ductus arteriosus subtypes.

OBJECTIVES: The purpose of this study was to explore the value of the transthoracic echocardiographic suprasternal view in the diagnosis of patent ductus arteriosus subtypes. METHODS: Sixty-five patients with a patent ductus arteriosus were examined using transthoracic echocardiographic suprasternal and parasternal views before ductus arteriosus closure. Diameters of the aortic and pulmonary sides of the ductus arteriosus were measured, and subtype diagnoses were made. The results were compared with those from digital subtraction angiography. RESULTS: The mean diameters ± SD of the aortic side of the ductus arteriosus were 8.31 ± 2.76, 10.87 ± 3.26, and 11.15 ± 3.29 for the parasternal view, the suprasternal view, and digital subtraction angiography, respectively, whereas the diameters of the pulmonary side were 5.69 ± 2.82, 5.75 ± 2.63, and 6.09 ± 2.78 mm. Of the 65 cases, 12, 19, and 19 were the funnel-type patent ductus arteriosus as evaluated with the parasternal view, the suprasternal view, and digital subtraction angiography. Detection on the parasternal view was lower than that on the suprasternal view (χ(2) = 5.14; P < .025). CONCLUSIONS: The diameter of the aortic side of a patent ductus arteriosus can be accurately detected on the superasternal view, which would be helpful for diagnosis of patent ductus arteriosus subtypes.

Myocardin is required for cardiomyocyte survival and maintenance of heart function.

Despite intense investigation over the past century, the molecular mechanisms that regulate maintenance and adaptation of the heart during postnatal development are poorly understood. Myocardin is a remarkably potent transcriptional coactivator expressed exclusively in cardiac myocytes and smooth muscle cells during postnatal development. Here we show that myocardin is required for maintenance of cardiomyocyte structure and sarcomeric organization and that cell-autonomous loss of myocardin in cardiac myocytes triggers programmed cell death. Mice harboring a cardiomyocyte-restricted null mutation in the myocardin gene (Myocd) develop dilated cardiomyopathy and succumb from heart failure within a year. Remarkably, ablation of the Myocd gene in the adult heart leads to the rapid-onset of heart failure, dilated cardiomyopathy, and death within a week. Myocd gene ablation is accompanied by dissolution of sarcomeric organization, disruption of the intercalated disc, and cell-autonomous loss of cardiomyocytes via apoptosis. Expression of myocardin/serum response factor-regulated myofibrillar genes is extinguished, or profoundly attenuated, in myocardin-deficient hearts. Conversely, proapoptotic factors are induced and activated in myocardin-deficient hearts. We conclude that the transcriptional coactivator myocardin is required for maintenance of heart function and ultimately cardiomyocyte survival.

[The Effect of Improved Culturing Method on the Detection Rate of Chromosome Karyotyping in Multiple Myeloma].

OBJECTIVE: To investigate an improved culturing method for karyotyping analysis, and increase the detection rate of cytogenetic abnormalities in patients with multiple myeloma (MM), so as to provide more powerful information for the clinical diagnosis, prognosis stratification, and individualized treatment of MM patients. METHODS: Eighty newly-diagnosed MM patients were enrolled and divided into two groups. In observation group, IL-6 (10 ng/ml) and GM-CSF (30 ng/ml) were supplemented in the culture medium, while no stimulating factor was added in control group. The samples from both groups were cultured for 72 hours under the same conditions, and their karyotypes were analyzed by G-banding. The detection rate of the cytogenetic abnormalities, as well as the corresponding characteristics were compared between the two groups. RESULTS: The detection rate of the chromosome aberrations was greatly increased in the observation group compared with the control group, the overall detection rate was 72.5% and 22.5%, respectively, as well as 80.0% and 19.2% in the subgroup of ≤60 years old, 68.0% and 28.6% in the subgroup of > 60 years old, which showed significant statistical differences (P<0.05). CONCLUSION: The modification of the culturing method with the addition of IL-6 (10 ng/ml) and GM-CSF (30 ng/ml) dual stimulating factors followed by incubation for 72 hours can effectively increase the detection rate of abnormal karyotypes in MM patients.

Effects of cold pressor-induced sympathetic stimulation on the mechanical properties of common carotid and femoral arteries in healthy males.

Our aim was to evaluate the effects of sympathetic excitation and elevation of blood pressure on mechanical properties of common carotid and femoral arteries by wave intensity analysis (WIA). The diameters and arterial stiffness parameters of right common carotid artery (RCCA) and right common femoral artery (RCFA) in healthy young men were measured by WIA at baseline and during cold pressor test (CPT). In addition, the blood pressure and heart rate were recorded simultaneously. The heart rates and blood pressures increased during CPT compared with baseline, while the pulse pressures remained unchanged. The diameters of RCCA increased slightly, while those of RCFA did not change. The Peterson's pressure modulus (Ep), augment index (AI), and pulse wave velocity from ß (PWVß) increased obviously, while arterial compliance (AC) decreased with no change in stiffness index (ß) of both arteries during CPT when compared with baseline. There was an obvious increase in pulse wave velocity from wave intensity (PWV_WI) of RCCA, while the PWV_WI of RCFA showed no significant change during CPT. The sympathetic nervous system exerts a more marked tonic restraint on RCFA than on RCCA. The Ep, AC, AI, PWVß of RCCA, and RCFA are much affected by variations in blood pressure and sympathetic status, while the ß of both arteries are less vulnerable to these factors and are more reliable in reflecting the actual arterial stiffness; The PWV_WI appears to be suitable only for evaluating the stiffness of RCCA instead of RCFA.

Analysis of Doppler flow spectra of the superior vena cava in a canine model of acute thromboembolic pulmonary hypertension.

We aimed to establish a canine model of acute thromboembolic pulmonary hypertension (ATEPH) and to explore the feasibility of diagnosing pulmonary hypertension (PH) through the Doppler flow spectra of the superior vena cava (SVC). A canine model of ATEPH was developed by infusing thrombus into the right femoral vein. The pulmonary arterial pressure was simultaneously measured via a right heart catheter with the guidance of ultrasound. The maximum systolic peak flow velocity (SPV), ventricular reverse peak flow velocity (VRPV), diastolic peak flow velocity (DPV), and atrial reverse peak flow velocity (ARPV) of the SVC were measured by transthoracic echocardiography. ATEPH was successfully established in 24 dogs (88.9%) with the pulmonary arterial systolic pressure (PASP) greater than 30 mmHg. ARPV increased significantly with the increase of PASP, and was positively correlated with PASP (P<0.001). The ARPV/SPV larger than 0.8 could be better adopted to identify all the subjects with PH in this study. The Doppler flow spectra of the SVC could be employed to assess the severity of ATEPH.

Deep learning applied to two-dimensional color Doppler flow imaging ultrasound images significantly improves diagnostic performance in the classification of breast masses: a multicenter study.

BACKGROUND: The current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images. METHODS: Taking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR-), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists. RESULTS: The accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87-0.91, 0.89-0.92, 0.87-0.91, and 0.86-0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%). CONCLUSIONS: The CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists. TRIAL REGISTRATION: Chictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.

Simvastatin inhibits angiotensin II-induced cardiac cell hypertrophy: role of Homer 1a.

1. The scaffolding protein Homer 1a is constitutively expressed in the myocardium, although its function in cardiomyocytes remains poorly understood. The aim of the present study was to investigate Homer 1a expression in hypertrophic cardiac cells and its role in angiotensin (Ang) II-induced cardiac hypertrophy. 2. After serum starvation for 24 h, cells were treated with 1 micromol/L simvastatin, 100 nmol/L angiotensin (Ang) II or their combination added to Dulbecco's modified Eagle's medium containing 0.5% serum. For combination treatment with AngII plus simvastatin, cells were exposed to simvastatin 12 h before the addition of AngII to the medium and cells were then incubated in the presence of both drugs for a further 24 h. Western blotting was used to determine Homer 1a protein expression. Hypertrophy was evaluated by determining the protein content per cell. 3. Homer 1a protein levels were upregulated following AngII-induced hypertrophy in H9C2 cells and neonatal rat cardiomyocytes, and these increases were augmented by simvastatin pretreatment. Concomitantly, simvastatin pretreatment inhibited extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and AngII-induced hypertrophy. 4. The inhibitory effects of simvastatin against AngII-induced hypertrophy were attenuated by Homer 1a silencing, suggesting that simvastatin suppresses cardiac hypertrophy in a Homer 1a-dependent manner. Furthermore, AngII-induced hypertrophy and ERK1/2 phosphorylation in neonatal rat cardiomyocytes were significantly inhibited following the overexpression of Homer 1a using an adenovirus. 5. These results suggest a possible role for Homer 1a in inhibiting cardiac hypertrophy perhaps in part through inhibition of ERK1/2 activation.

[Prognosis and Genetic Characteristics of Patients with Plasma Cell Leukemia].

OBJECTIVE: To evaluate the clinical characteristics, genetic abnormalities, treatment efficacy and prognostic factors in patients with plasma cell leukemia(PCL). METHODS: 30 patients diagnosed as PCL in our hospital from January 1993 to December 2019 were enrolled, and the clinical characteristics, laboratory findings, therapeutic regimes, and survival data of the patients were retrospectively analyzed. RESULTS: The median age of the 30 patients was 56.5 (28-80) years old, among them, 25 patients were primary plasma cell leukemia, and 5 patients were secondary plasma cell leukemia. Complex karyotypes and subdiploids were most common in cytogenetic abnormalities. Among the 20 cases of chromosome G banding, 11 (55%) cases were complex karyotypes and 8 (40%) cases were hypodiploid. Fluorescent in situ hybridization (FISH) test showed that among 11 cases, 6 cases showed 17p13 deletion, 8 cases showed at least two kinds of abnormalities, which including t (14; 16), t (8; 14), t (11;14), 17p13 deletion, and 13q14 deletion. The median overall survival (OS) time was 10.5 months for all patients. The median OS time of the patients in ECOG score ≤ 2 group was 21.5 months, which was significantly longer than those in the ECOG score>2 group(1.2 months) (P=0.017). The median OS time of the patients treated with novel agents (including proteasome inhibitor and/or immunomodulator) was 24.9 months, which was significantly longer than the patients treated with traditional chemotherapy group(10.5 months) (P＜0.001). For the patients treated with novel agents, the median OS time of patients accepted two novel agents combination was 30.9 months, which was longer than those of single novel agent(11.5 months) (P=0.021). The effect of genetic abnormolity to the OS of the patients showed no statistical difference. Multivariate statistical analysis showed that ECOG score>2 was the independent prognostic factor of plasma cell leukemia patients. There were two patients underwent allogeneic hematopoietic stem cell transplantation in the study,but died due to the pulmonary infection within 6 months after transplantation. CONCLUSION: In the era of novel agents, ECOG score is an independent prognostic factor of plasma cell leukemia. Multiple novel agents treatment should be underwent as soon as possible to improve the prognosis of the patients. Pulmonary infection is a common factor that cause the death of the patients after allogeneic hematopoietic stem cell transplantation.