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Background. Abnormal proliferation of vascular smooth muscle cells (VSMCs) is an important cause of vascular stenosis. The study explored the mechanism of inhibition of vascular stenosis through the molecular mechanism of smooth muscle cell phenotype transformation. Methods. Coronary heart disease-related genes were screened by bioinformatics, and the target genes of miR-654-5p were predicted by dual-luciferase method and immunofluorescence method. miR-654-5p mimic stimulation and transfection of TCF21 and MTAP into cells. SonoVue microbubble sonication was used to deliver miR-654-5p into cells. Cell proliferation, migration, and invasion were detected by CCK-8, wound scratch, and Transwell. HE and IHC staining were performed to study the effect of miR-654-5p delivery via SonoVue microbubble ultrasound on vessel stenosis in a model of arterial injury. Gene expression was determined by qRT-PCR and WB. Results. TCF21 and MTAP were predicted as the target genes of miR-654-5p. Cytokines induced smooth muscle cell proliferation, migration, and invasion and promoted miR-654-5p downregulation; noticeably, downregulated miR-654-5p was positively associated with the cell proliferation and migration. Overexpression of TCF21 promoted proliferation, invasion, and migration, and mimic reversed such effects. miR-654-5p overexpression delivered by SonoVue microbubble ultrasound inhibited proliferation, migration, and invasion of cells. Moreover, in arterial injury model, we found that SonoVue microbubble ultrasound transmitted miR-654-5p into the arterial wall to inhibit arterial thrombosis and stenosis, while TCF21 was inhibited. Conclusion. Ultrasound delivery of miR-654-5p via SonoVue microbubbles was able to inhibit arterial thrombosis and stenosis by targeting TCF21.

Background Intravoxel incoherent motion (IVIM) can provide quantitative information about water diffusion and perfusion that can be used to evaluate hepatic injury, but it has not been studied in hepatic injury induced by intestinal ischemia–reperfusion (IIR). Dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) can provide perfusion data, but it is unclear whether it can provide useful information for assessing hepatic injury induced by IIR. Purpose To examine whether IVIM and DCE‐MRI can detect early IIR‐induced hepatic changes, and to evaluate the relationship between IVIM and DCE‐derived parameters and biochemical indicators and histological scores. Study Type Prospective pre‐clinical study. Population Forty‐two male Sprague–Dawley rats. Field Strength/Sequence IVIM‐diffusion‐weighted imaging (DWI) using diffusion‐weighted echo‐planar imaging sequence and DCE‐MRI using fast spoiled gradient recalled‐based sequence at 3.0 T. Assessment All rats were randomly divided into the control group (Sham), the simple ischemia group, the ischemia–reperfusion (IR) group (IR1h, IR2h, IR3h, and IR4h) in a model of secondary hepatic injury caused by IIR, and IIR was induced by clamping the superior mesenteric artery for 60 minutes and then removing the vascular clamp. Advanced Workstation (AW) 4.6 was used to calculate the imaging parameters (apparent diffusion coefficient [ADC], true diffusion coefficient [D], perfusion‐related diffusion [D *] and volume fraction [f]) of IVIM. OmniKinetics (OK) software was used to calculate the DCE imaging parameters (K trans, K ep, and V e). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed with an automatic biochemical analyzer. Superoxide dismutase (SOD) activity was assessed using the nitro‐blue tetrazolium method. Malondialdehyde (MDA) was determined by thiobarbituric acid colorimetry. Histopathology was performed with hematoxylin and eosin staining. Statistical Tests One‐way analysis of variance (ANOVA) and Bonferroni post‐hoc tests were used to analyze the imaging parameters and biochemical indicators among the different groups. Pearson correlation analysis was applied to determine the correlation between imaging parameters and biochemical indicators or histological score. Results ALT and MDA reached peak levels at IR4h, while SOD reached the minimum level at IR4h (all P

Purpose Atherosclerosis is the leading cause of cardiovascular diseases (CVD) with high incidence rate and mortality rate. Long non-coding RNAs (lncRNAs) are important functional molecules in atherosclerosis. Present study aimed to explore the functional role and underlying mechanism of ZFAS1 in atherosclerosis. Methods The in-vitro cell model of atherosclerosis was established by using oxidized low-density lipoprotein (ox-LDL) to induce THP-1 macrophage-derived foam cells. qRT-PCR measured the mRNA levels of ZFAS1, miR-654-3p, ADAM10 and RAB22A. Western blot detected the protein levels of ADAM10 and RAB22A. The levels of IL-1β, IL-6 and TNF-ɑ (inflammatory biomarkers) were tested with ELISA assay. Detection of cholesterol efflux rate was experimented. The interaction between RNAs was affirmed with luciferase reporter and RNA pull-down experiments. Results The expression of ZFAS1 was significantly up-regulated in in-vitro cell model of atherosclerosis at a dose- and time-dependent manner. Knockdown of ZFAS1 impaired inflammatory responses and promoted cholesterol efflux rate. Overexpression of ZFAS1 accelerated inflammatory responses and hampered cholesterol efflux rate. Then, the cytoplasmic role of ZFAS1 was revealed. By bio-informatics analysis and mechanism assays, miR-654-3p was identified to bind with ZFAS1. Moreover, ADAM10 and RAB22A were targeted and suppressed by miR-654-3p. ZFAS1 served as a ceRNA to positively regulate ADAM10 and RAB22A expression through endogenously sponging miR-654-3p. Conclusion In conclusion, ZFAS1 elevated ADAM10/RAB22A expression to reduce cholesterol efflux rate and facilitate inflammatory responses in atherosclerosis at a miR-654-3p-dependent way, suggesting a prospective treatment method for amelioration of atherosclerosis.

Background and purposeNuclear grades of clear cell renal cell carcinoma (ccRCC) are usually confirmed by invasive methods. Radiomics is a quantitative tool that uses non-invasive medical imaging for tumor diagnosis and prognosis. In this study, a radiomics approach was proposed to analyze the association between preoperative computed tomography (CT) images and nuclear grades of ccRCC.MethodsOur dataset included 320 ccRCC patients from two centers and was divided into a training set (n = 124), an internal test set (n = 123), and an external test set (n = 73). A radiomic feature set was extracted from unenhanced, corticomedullary phase, and nephrographic phase CT images. The maximizing independent classification information criteria function and recursive feature elimination with cross-validation were used to select effective features. Random forests were used to build a final model for predicting nuclear grades, and area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of radiomic features and models.ResultsThe radiomic features from the three CT phases could effectively distinguished the four nuclear grades. A combined model, merging radiomic features and clinical characteristics, obtained good predictive performances in the internal test set (AUC 0.77, 0.75, 0.79, and 0.85 for the four grades, respectively), and performance was further confirmed in the external test set, with AUCs of 0.75, 0.68, and 0.73 (no fourth-level data).ConclusionThe combination of CT radiomic features and clinical characteristics could discriminate the nuclear grades in ccRCC, which may help in assisting treatment decision making.

Objective. To investigate the association between inflammation and clinical outcomes of coronary artery bypass grafting (CABG) in diabetic patients. Methods. A total of 300 diabetic patients with coronary heart disease who underwent CABG were selected. Patients were divided into a group with cardiovascular events (32 in the MACCE group) and a group without cardiovascular events (268 in the non-MACCE group) according to whether cardiovascular events occurred within 30 days. The differences in clinical parameters; serum levels of TNF-α, IL-6, IL-18, IL-1β, and CRP; factors associated with the occurrence of MACCE; and risk factors affecting the midterm all-cause mortality of patients were compared between the two groups. Results. The serum levels of TNF-α, IL-6, IL-18, and CRP in the MACCE group were significantly higher than those in the non-MACCE group ( p < 0.05 ). Gender, smoking, hyperlipidemia, duration of diabetes, and levels of TNF-α, IL-6, IL-18, and CRP were closely related to the occurrence of MACCE. The Kaplan-Meier survival analysis evaluation results showed that the levels of IL-6 and CRP significantly affected the midterm all-cause mortality rate ( p < 0.05 ). Multivariate Cox regression analysis showed that the advanced age, hypertension, hyperlipidemia, long duration of diabetes, elevated serum IL-6, and CRP levels could be used as risk factors for midterm all-cause mortality. Conclusions. Inflammation levels in diabetic patients are associated with complications and midterm all-cause mortality in patients undergoing coronary artery bypass grafting.

Magnetic resonance imaging is widely used to identify and monitor thrombi in grafted vessels following coronary artery bypass grafting surgery (CABG). We produced a biosensor, P1Cm-SPIO-Cy5.5, composed of P1Cm peptide, superparamagnetic iron oxide nanoparticles (SPIO), and polyethylene glycol (PEG), for use in MRI thrombus imaging. Activated platelets induced by adenosine diphosphate were used for combination tests in vitro. A rat model of common carotid artery thrombosis was used for anti-thrombus experiments in vivo. P1Cm-SPIO-Cy5.5 remains stable in vitro and has good anticoagulation capacity. It can bind specifically to activated platelets and thrombi. In rats that underwent bypass surgery, P1Cm-SPIO-Cy5.5 could detect and label thrombi over a long period, and prevent thrombosis in grafted vessels. P1Cm-SPIO-Cy5.5 improved cardiac function in rats following CABG surgery. P1Cm-SPIO-Cy5.5 is a potential sensor for use in MRI for the early diagnosis and prevention of thrombosis after CABG surgery.

Background Acute myocardial infarction (MI) is a main cause of emergency death in the world. MicroRNAs (miRs/miRNAs) are a series of small non-coding RNA molecules, which regulate cardiovascular disorders that involve MI. In this study, we explored the function of miR-200a in MI treatment. Methods We observed down-regulation of miR-200a levels and up-regulation of Keap1 and β-catenin levels in H2O2-treated newborn murine ventricular cardiomyocytes (NMVCs) and the infarcted heart tissues of MI mouse models, compared to the non-treated NMVCs and normal heart tissues of healthy mice. Results CCK-8 and colony formation assays indicated the reduction in NMVC vitality due to H2O2 treatment and the recovery of cell vitality due to miR-200a overexpression, respectively. Flow cytometry with Annexin and PI staining indicated the inhibition of H2O2-triggered cell apoptosis through ectopically expressed miR-200a. Western blotting and ELISA analyses that detected pro-inflammatory cell factors [interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α] confirmed that miR-200a prevented H2O2-induced NMVC inflammation. Moreover, miR-200a inhibited up-regulation of Keap1 and β-catenin expression in H2O2-treated NMVCs by directly binding with the 3′-UTR regions of both Keap1 and β-catenin. Furthermore, overexpression of Keap1 and β-cateninin in H2O2-treated NMVCs with recovered miR-200a elevated inflammation and apoptosis, respectively. Conclusion The results showed that miR-200a expression was inhibited in murine cardiomyocytes due to H2O2 stress in MI cardiac tissues and overexpressed miR-200a could protect the cells from death by regulating the Keap1/Nrf2 and β-catenin signal transduction pathways.

Reverberation reduces speech quality, and therefore causes inconveniency to listeners, especially those using assistive hearing devices. To enhance the quality of reverberant speech, a significant step is speech quality assessment, most of which are based on subjective judgements. Subjective evaluations vary with listeners' perception, emotional and mental states. To obtain an objective assessment of speech quality in reverberation, this work carried out an event related potential (ERP) study using a passive oddball paradigm. Listeners were presented with anechoic speech as standard stimuli mixed with reverberant speech under different levels of reverberation as deviant stimuli. The ERP responses reveal how human-beings' subconsciousness interacts with different levels of reverberation in the perceived speech. Results showed that the peak amplitude of P300 in ERP responses followed the variation of reverberation time in reverberant speech, providing evidence that P300 in ERP responses could work as a neural surrogate of reverberation time in objective speech quality assessment.

Most recent studies attribute residual limb pain to peripheral pathological changes of the stump. However, in this paper, we focus on its associations with the residual limb length, usage, as well as the metabolic and functional alterations of the brain. The secondary somatosensory cortex (S2), one important area involved in pain intensity discrimination, was selected as the region of interest. Twenty-two upper-limb amputees were recruited and divided into two groups, i.e., amputees with residual limb pain (9/22) and without residual limb pain (13/22). The residual limb length, usage, as well as the metabolite concentration, resting-state activity and BOLD responses to the tactile stimulation in the contralateral S2, were compared between the two groups and correlated with the pain intensity. The amputees with residual limb pain showed significantly shorter length and less usage of the residual limb than the amputees without residual limb pain, and the pain intensity was significantly negatively correlated with the residual limb length and usage. In addition, the pain intensity was significantly correlated with the tNAA/tCr ratio, resting-state fALFF in the slow-4 band, and BOLD response to the tactile stimulation in the contralateral S2, although there were no significant group differences. Regression analysis suggested that residual limb pain is associated with shorter residual limb length and less residual limb usage.

Previous studies have indicated that amputation induces reorganization of functional brain network. However, the influence of amputation on structural brain network remains unclear. In this study, using diffusion tensor imaging (DTI), we aimed to investigate the alterations in fractional anisotropy (FA) network after unilateral upper-limb amputation. We acquired DTI from twenty-two upper-limb amputees (15 dominant-side and 7 nondominant-side amputees) as well as fifteen healthy controls. Using DTI tractography and graph theoretical approaches, we examined the topological changes in FA network of amputees. Compared with healthy controls, dominant-side amputees showed reduced global mean strength, increased characteristic path length, and decreased nodal strength in the contralateral sensorimotor system and visual areas. In particular, the nodal strength of the contralateral postcentral gyrus was negatively correlated with residual limb usage, representing a use-dependent reorganization. In addition, the nodal strength of the contralateral middle temporal gyrus was positively correlated with the magnitude of phantom limb sensation. Our results suggested a degeneration of FA network after dominant-side upper-limb amputation.

Coronary artery disease (CAD) is a major and common disease that poses a threat to human health. Recent studies suggested that epicardial fat may have an important role in the pathogenesis of CAD. Therefore, the association between epicardial fat volume (EFV) and left ventricular function with CAD was investigated in the present study. A total of 61 patients with suspected CAD who underwent CT scanning were enrolled. Baseline data, parameters of left heart function and EFV of the subjects were collected and analyzed. The degree of coronary artery lesions was assessed using the Gensini score. Pearson's correlation analysis and a logistic regression model were applied to assess the association between EFV and risk factors for CAD, the Gensini score and left ventricular function index. A total of 29 female and 32 male subjects with a median age of 63 years were enrolled. The median body mass index (BMI) of the subjects was 23.37 kg/m2 and the median EFV was 86.41 cm3. It was revealed that risk factors of CAD, specially hypertension, diabetes mellitus, dyslipidemia, history of myocardial infarction and smoking, had no significant association with the EFV (P>0.05); however, the EFV was significantly positively correlated with the BMI (r=0.479, P

Aim To systematically investigate the multisite reproducibility, test–retest reliability, and observer variability of non-respiratory-gated four-dimensional (4D) flow magnetic resonance imaging (MRI) in the thoracic great vessels for the assessment of blood flow and peak velocity. Materials and methods Electrocardiogram (ECG)-gated 4D flow MRI data were acquired without respiratory gating in 10 healthy volunteers. To analyse multisite reproducibility, 4D flow was scanned at three different sites using a 3 T GE MRI machine with identical protocols for the group of participants. In addition, to evaluate test–retest reliability, the same volunteers were scanned in each centre during a second visit. Data analysis included calculation of peak systolic velocity and time-resolved and total flow of both the ascending aorta and pulmonary artery. Two observers conducted the above measurements to assess the interobserver variability. Results Multisite, test–retest, interobserver agreement were good for the calculation of total flow and peak systolic velocity (mean differences Conclusion Non-respiratory-gated 4D MRI-based assessment of aortic and pulmonary blood flow can be performed with good reproducibility. It may facilitate the potential clinical application of this technique.

Diabetes is often associated with impairments in brain functioning. However, the injury of specific functioning areas of the brain is not clear. To address this problem, the present study was designed to investigate possible brain functioning change in specific brain areas, particularly in areas associated with vision function, in patients with proliferative and nonproliferative diabetic retinopathy (PDR and NPDR) using the diffusion-weighted imaging technology. Conventional MRI was performed in 45 diabetic patients, 30 of whom had diabetic retinopathy (DR) involvement (half PDR, and half NPDR) and 15 of whom were diabetic patients without retinopathy and with normal ophthalmologic examination. The apparent diffusion coefficient (ADC) values were calculated in the orbitofrontal cortex (OFC), cingulated gyrus, thalamus, dorsomedial and dorsolateral frontal cortex, and corona radiate. The ADC values of the OFC, cingulated gyrus, and visual cortex were significantly increased in patients with PDR and NPDR compared with both patients without retinopathy and the control group (P

The circulating miRNAs are dysregulated in non-small cell lung cancer (NSCLC) and have great promise for clinical diagnosis. The aim of this study was to screen and evaluate the reliability and diagnostic efficiency of candidate serum miRNAs for NSCLC diagnosis. We found that miR-21 and let-7a were significantly dysregulated in NSCLC patients (P

To study the metabolic changes following amputation, we investigated the metabolite concentrations in the secondary somatosensory cortex and thalamus from twenty-three upper limb amputees and sixteen age-matched healthy controls using proton magnetic resonance spectroscopy (MRS). The ratios of major metabolites to the creatine (Cr) peak were quantified to indicate metabolite levels. Compared with the healthy controls, the amputees showed significantly reduced NAA/Cr and Cho/Cr ratios in the secondary somatosensory cortex and thalamus contralateral to the amputation side, indicating neuronal loss and dysfunctions in these brain regions due to the loss of sensory input. Meanwhile, the stump sensation was found to be positively correlated with NAA/Cr ratio and negatively correlated with GSH/Cr ratio in the thalamus. The results suggested that both the thalamus and somatosensory cortex may undergo metabolic changes after amputation.

Summary Objective To investigate exenatide, a GLP-1 analogue, compared with acarbose, for intra-abdominal fat reduction in patients with obesity and type-2 diabetes. Methods This randomized controlled trial included 36 patients with obesity and type-2 diabetes, who were metformin-unresponsive, receiving metformin/exenatide (GLP-1 group) or metformin/acarbose (control group) for 3 months. Primary end-point: intra-abdominal fat content from baseline to 3 months; Secondary end-points: changes in fasting blood glucose, glycated haemoglobin (HbAlc), fasting insulin, blood lipids, weight, body mass index, and inflammatory cytokines from baseline to 3 months. Results Intra-abdominal fat content decreased in the GLP-1 group from baseline to 3 months (17,947±5804; 13,717±3628mm 2 , P=0.001, respectively), but was not significantly reduced in the control group (P=0.197) and at 3 months post-treatment, it was significantly lower in the GLP-1 group than control group (P=0.043). Glucose control, measured by HbA1c (GLP-1: 9.72±1.38; 7.09±0.60%, P Conclusion Combined exenatide/metformin reduced intra-abdominal fat content, and enhanced insulin resistance and inflammatory status in patients with obesity and type-2 diabetes, representing a novel treatment regimen.

Currently, human subjects performed a cognitive reappraisal of emotion task while being scanned with functional magnetic resonance imaging (fMRI). Both sparse spectral clustering and independent component analysis (ICA) were applied to characterize the interactions between brain areas involved in cognitive reappraisal of emotion. The results revealed that the sparse spectral clustering method can get a higher sensitivity of polymerization compared with ICA. Furthermore, Voxel-based aggregation index (VBAI) has been presented to confirm that sparse spectral clustering is more excellent in identifying correlation patterns with weaker connectivity, such as temporal network. Thus, the study concluded that sparse spectral clustering provides a more practical and accurate way for researching brain functional connectivity in the process of emotional stimuli.

SummaryBackground and aim To evaluate image quality and radiation dosage in coronary CT angiography using 80-kVp tube voltage combined with low-concentration contrast media (CM) and iterative reconstruction (IR) for coronary CT angiography (CCTA) and employing dual-source CT without heart-rate control. Methods 154 patients were randomly assigned to Group A (Control Group, 120-kVp tube voltage, high-concentration CM and filtered back projection reconstruction) and Group B (Low-Dose Group, 80 kVp, low-concentration CM and iterative construction). Two experienced radiologists double-blindly evaluated the following parameters: CT attenuation, signal-noise ratio (SNR), contrast-noise ratio (CNR), radiation dose, size-specific dose estimates (SSDE) and total iodine intake. Pearson correlation analysis was used to assess the relationship between SSDE and BMI. Results 98.1% vessel segments in Group A and 97.6% in Group B passed diagnostics, indicating no significant differences; the average aorta scores and CT attenuation values showed no significant differences between groups. Similar SNR and CNR results were obtained for the two groups, although values were slightly lower in Group A compared with Group B. The Effective Dose in Group B was 63% lower than that in Group A (P