Genetic Variation of the Kalirin Gene is Associated with ICAS in the Chinese Population.

Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of ischemic stroke (IS), especially in recurrent patients. Several studies have demonstrated an intimate association between the genetic mutation of the KALRN gene and IS. The main aim of this study was to clarify the relationship between three single nucleotide polymorphisms (SNPs) of KALRN and ICAS in a northern Chinese population and further explore the underlining mechanism. The relationship between each SNP and ICAS and the related components were examined in five models (co-dominant, dominant, recessive, heterozygous, and additive). Multivariate logistic regression models were applied and adjusted for 10,000 permutation tests. Haplotype regression analysis was performed to determine the associations between haplotypes and the severity of ICAS. qRT-PCR was used to confirm the mRNA level of Kalirin. SNP rs6438833 of the Kalirin gene in the additive model was associated with ICAS (OR = 1.642, 95%CI: 1.129-2.388, PDom = 0.048). After performing 10,000 permutations, the result showed a trend toward statistical significance (Pper = 0.048). Haplotypes of the KALRN gene were not significantly associated with ICAS (global significance, p = 0.090). qRT-PCR showed that the expression of KALRN 9 in IS patients was almost threefold the control group (p < 0.0005). SNPs of the KALRN gene are associated with ICAS in the northern Chinese population.

Contrast-Enhanced Ultrasound Imaging Quantification of Adventitial Vasa Vasorum in a Rabbit Model of Varying Degrees of Atherosclerosis.

This study used an atherosclerotic rabbit model to investigate the feasibility of quantifying adventitial vasa vasorum (VV) via contrast-enhanced ultrasound (CEUS) imaging to identify early atherosclerosis. Recent evidence has linked adventitial VV with atherosclerotic plaque progression and vulnerability. A growth in VV density has been detected preceding intimal thickening and even endothelial dysfunction. In our study, carotid atherosclerosis rabbit models were used, and animals underwent CEUS imaging at the end of the atherosclerotic induction period. Normalized maximal video-intensity enhancement (MVE) was calculated to quantify VV density. After CEUS imaging, animals were euthanized, and their carotids were processed for histopathological analysis following staining for CD31 and VEGF. Adventitial normalized MVE increased as atherosclerosis progressed (p < 0.001), and normalized MVE also progressed, demonstrating a linear correlation with histological findings (r = 0.634, p < 0.001 for VEGF-positive; r = 0.538, p < 0.001 for CD31-positive). Thus, we histologically validated that CEUS imaging can be used to quantify the development of adventitial VV associated with atherosclerosis progression. This method can be used for monitoring the VV to detect early atherosclerosis.

Real-Time Elastography Visualization and Histopathological Characterization of Rabbit Atherosclerotic Carotid Arteries.

To evaluate the feasibility of non-invasive vascular real-time elastography imaging (RTE) in visualizing the composition of rabbit carotid atherosclerotic plaque as determined by histopathology, a rabbit model of accelerated carotid atherosclerosis was used. Thirty rabbits were randomly divided into two groups of 15 rabbits each. The first group was fed a cholesterol-rich diet and received balloon-induced injury the left common carotid artery endothelium, whereas the second group only received a cholesterol-rich diet. The rabbits were all examined in vivo with HITACHI non-invasive vascular real-time elastography (Hi-RTE) at baseline and 12 wk, and results from the elastography were compared with American Heart Association histologic classifications. Hi-RTE and the American Heart Association histologic classifications had good agreement, with weighted Cohen's kappa (95% confidence internal) of 0.785 (0.649-0.920). Strains of segmented plaques that were stained in different colors were statistically different (p < 0.0001). The sensitivity and specificity of elastograms for detecting a lipid core were 95.5% and 61.5%, respectively, and the area under the receiver operating characteristic curve was 0.789, with a 95% confidence interval of 0.679 to 0.876. This study is the first to indicate the feasibility of utilizing Hi-RTE in visualizing normal and atherosclerotic rabbit carotid arteries non-invasively. This affordable and reliable method can be widely applied in research of both animal and human peripheral artery atherosclerosis.

Three-dimensional transvaginal tomographic ultrasound imaging for cervical cancer staging.

The objective of this study was to investigate the feasibility of using 3-D transvaginal tomographic ultrasound imaging (TUI) to stage patients with cervical carcinoma. Eighty women with cervical cancer who underwent transvaginal TUI examinations were enrolled. In all patients, cancer was confirmed pre-operatively by pathologic examination. Staging on the basis of clinical features, ultrasonography and magnetic resonance imaging was performed according to the International Federation of Gynecology and Obstetrics (FIGO) staging system. Clinical, TUI and magnetic resonance imaging staging was compared with that based on histology. Depth of invasion into the stroma was measured by TUI in 52 cases and compared with pathologic results. An interclass correlation coefficient was used to analyze reproducibility. In total, all 80 patients underwent surgical treatment. The accuracy of pre-operative staging, compared with histologic findings, was 92.50% for TUI, 82.50% for magnetic resonance imaging and 78.75% for clinical examination. The mean depth of lesions as measured with TUI was 12.5 ± 6.2 mm (range: 3.5-40.0 mm), and that measured on histology was 10.5 ± 8.0 mm (range: 3.0-40.0 mm). The interclass correlation coefficient of the two methods was 0.933 (95% confidence interval: 0.887-0.961). Pre-operative TUI is promising as a method for pre-operative staging of cervical carcinomas. TUI can also reliably assess lesion depth.

KALRN Rare and Common Variants and Susceptibility to Ischemic Stroke in Chinese Han Population.

Stroke is the second most common cause of mortality worldwide, and it is a major cause of physical disability. Several genome-wide association studies have yielded numerous common variants which increase the risk of ischemic stroke, including the Kalirin-coding gene, KALRN. KALRN strongly associates with early-onset coronary artery disease and atherosclerosis and plays an important role in stroke in the European population. In this study, we analyzed four KALRN gene SNPs in 503 ischemic stroke patients and 493 control subjects, separating the patients into separate research groups based on comorbidity with hypertension or diabetes and stroke type (atherosis or lacunar and combination type). We found a rare variant of KALRN, rs11712619, that associated with lacunar stroke in the northern Chinese Han population with an average-risk allele frequency 0.009 (OR 2.95, 95 % CI 1.08-8.01, p = 0.028). However, after adjusting for relevant factors, including sex, age, body mass index, dyslipidemia, alcohol consumption, and smoking, this association was not evident. Additionally, the KALRN variant rs6438833 was associated with ischemic stroke, ischemic stroke comorbid with diabetes, and lacunar stroke after adjusting for the relevant factors (p = 0.046, p = 0.019 and p = 0.046, respectively), which remained significant after 10,000 permutation procedure test (p' = 0.047, p' = 0.018 and p' = 0.048, respectively). The association of these rare and common variants of KALRN with ischemic stroke in northern Chinese Han population offers insight for potential therapeutic research.