HIF-1α knockdown attenuates inflammation and oxidative stress in ischemic stroke male rats via CXCR4/NF-κB pathway.

BACKGROUND: Hypoxia inducible factor-1α (HIF-1α) is a sensitive indicator of oxygen homeostasis, of which the expression elevates following hypoxia/ischemia. This study reveals the specific mechanisms underlying the effects of HIF-1α on ischemic stroke (IS). METHODS: IS model was established using middle cerebral artery occlusion (MCAO)-modeled male rats and oxygen glucose deprivation/reoxygenation (OGD/R)-treated mice hippocampal cells HT22, followed by the silencing of HIF-1α and the overexpression of C-X-C motif chemokine receptor 4 (CXCR4) and nuclear factor-kappa B (NF-κB). Following the surgery, Garcia's grading scale was applied for neurological evaluation. Cerebral infarcts and injuries were visualized using 2,3,5-triphenyltetrazolium chloride and hematoxylin-eosin staining. The levels of tumor necrosis factor-α, Interleukin (IL)-6, IL-1ß, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine, were calculated via ELISA. MTT assay and lactate dehydrogenase (LDH) assay kit were adopted to determine the viability and cytotoxicity of OGD/R-modeled cells. Reactive oxygen species (ROS) generation was evaluated using a 2'-7'dichlorofluorescin diacetate (DCFH-DA) probe. The levels of HIF-1α, CXCR4, and NF-κB p65 were quantified via Western blot and immunofluorescence, respectively. RESULTS: HIF-1α knockdown improved Garcia's score, attenuated the cerebral infarct, inflammation, and ROS generation, and alleviated the levels of inflammatory cytokines and CXCR4/NF-κB p65 in MCAO-modeled rats. Such effects were reversed following the overexpression of CXCR4 and NF-κB. Also, in OGD/R-treated HT22 cells, HIF-1α silencing diminished the cytotoxicity and ROS production and reduced the expressions of CXCR4/NF-κB p65, while promoting viability. However, CXCR4/NF-κB p65 overexpression did the opposite. CONCLUSION: HIF-1α knockdown alleviates inflammation and oxidative stress in IS through the CXCR4/NF-κB pathway.

Four-quadrant fast compressive tracking of breast ultrasound videos for computer-aided response evaluation of neoadjuvant chemotherapy in mice.

BACKGROUND AND OBJECTIVE: Neoadjuvant chemotherapy (NAC) is a valuable treatment approach for locally advanced breast cancer. Contrast-enhanced ultrasound (CEUS) potentially enables the assessment of therapeutic response to NAC. In order to evaluate the response accurately, quantitatively and objectively, a method that can effectively compensate motions of breast cancer in CEUS videos is urgently needed. METHODS: We proposed the four-quadrant fast compressive tracking (FQFCT) approach to automatically perform CEUS video tracking and compensation for mice undergoing NAC. The FQFCT divided a tracking window into four smaller windows at four quadrants of a breast lesion and formulated the tracking at each quadrant as a binary classification task. After the FQFCT of breast cancer videos, the quantitative features of CEUS including the mean transit time (MTT) were computed. All mice showed a pathological response to NAC. The features between pre- (day 1) and post-treatment (day 3 and day 5) in these responders were statistically compared. RESULTS: When we tracked the CEUS videos of mice with the FQFCT, the average tracking error of FQFCT was 0.65 mm, reduced by 46.72% compared with the classic fast compressive tracking method (1.22 mm). After compensation with the FQFCT, the MTT on day 5 of the NAC was significantly different from the MTT before NAC (day 1) (p = 0.013). CONCLUSIONS: The FQFCT improves the accuracy of CEUS video tracking and contributes to the computer-aided response evaluation of NAC for breast cancer in mice.

Artificial intelligence-based myocardial texture analysis in etiological differentiation of left ventricular hypertrophy.

BACKGROUND: Transthoracic echocardiography (TTE) is widely used in clinics to evaluate left ventricular hypertrophy (LVH). However, TTE is usually insufficient for the etiological diagnoses when morphological and functional features are nonspecific. With the booming of computer science and artificial intelligence (AI), previous literature has reported the application of radiomics based on cardiac magnetic resonance imaging, cardiac computed tomography and TTE in diagnosing several myocardial abnormalities, such as myocardial infarction, myocarditis, cardiac amyloidosis, and hypertrophic cardiomyopathy (HCM). In this study, we explored the possibility of using myocardial texture features in differentiating HCM, hypertensive heart disease (HHD) and uremic cardiomyopathy (UCM) based on echocardiography. To our knowledge, this was the first study to explore TTE myocardial texture analysis for multiple LVH etiology differentiation. METHODS: TTE images were reviewed retrospectively from January 2018 to collect 50 cases for each group of HHD, HCM and UCM. The apical four chamber view was retrieved. Seventeen first-order statistics and 60 gray level co-occurrence matrix (GLCM) features were extracted for statistics and classification test by support vector machine (SVM). RESULTS: Of all the parameters, entropy of brightness (EtBrt), standard deviation (Std), coefficient of variation (CoV), skewness (Skew), contrast7 (Cont7) and homogeneity5 (Hm5) were found statistically significant among the three groups (all P<0.05) and with acceptable reproducibility (intraobserver and interobserver ICC >0.50). As a result, HCM showed the most homogeneous myocardial texture, and was significantly different from HHD and UCM (all six features: P≤0.005). HHD appeared slightly more homogeneous than UCM, as only EtBrt and CoV were significant (P=0.011 and P=0.008). According to higher areas under the receiver operating characteristic curve (AUC) (>0.50), EtBrt, Std, and CoV were selected for test of classification as a combination of features. The AUC derived from SVM model was slightly improved compared with those of EtBrt, Std and CoV individually. CONCLUSIONS: AI-based myocardial texture analysis using ultrasonic images may be a potential approach to aiding LVH etiology differentiation.

Ultrasound Radiomics Effective for Preoperative Identification of True and Pseudo Gallbladder Polyps Based on Spatial and Morphological Features.

Purpose: To explore the value of ultrasound radiomics in the preoperative identification of true and pseudo gallbladder polyps and to evaluate the associated diagnostic accuracy. Methods: Totally, 99 pathologically proven gallbladder polyps in 96 patients were enrolled, including 58 cholesterol polyps (55 patients) and 41 gallbladder tubular adenomas (41 patients). Features on preoperative ultrasound images, including spatial and morphological features, were acquired for each lesion. Following this, two-stage feature selection was adopted using Fisher's inter-intraclass variance ratios and Z-scores for the selection of intrinsic features important for differential diagnosis achievement with support vector machine use. Results: Eighty radiomic features were extracted from each polyp. Eight intrinsic features were identified after two-stage selection. The contrast 14 (Cont14) and entropy 6 (Entr6) values in the cholesterol polyp group were significantly higher than those in the gallbladder adenoma group (4.063 ± 1.682 vs. 2.715 ± 1.867, p < 0.001 for Cont14; 4.712 ± 0.427 vs. 4.380 ± 0.720, p = 0.003 for Entr6); however, the homogeneity 13 (Homo13) and energy 8 (Ener8) values in the cholesterol polyp group were significantly lower (0.500 ± 0.069 vs. 0.572 ± 0.057, p < 0.001 for Homo13; 0.050 ± 0.023 vs. 0.068 ± 0.038, p = 0.002 for Ener8). These results indicate that the pixel distribution of cholesterol polyps was more uneven than that of gallbladder tubular adenomas. The dispersion degree was also significantly lower in the cholesterol polyp group than the gallbladder adenoma group (0.579 ± 0.054 vs. 0.608 ± 0.041, p = 0.005), indicating a lower dispersion of high-intensity areas in the cholesterol polyps. The long axis length of the fitting ellipse (Maj.Len), diameter of a circle equal to the lesion area (Eq.Dia) and perimeter (Per) values in the cholesterol polyp group were significantly lower than those in the gallbladder adenoma group (0.971 ± 0.485 vs. 1.738 ± 0.912, p < 0.001 for Maj.Len; 0.818 ± 0.393 vs. 1.438 ± 0.650, p < 0.001 for Eq.Dia; 2.637 ± 1.281 vs. 5.033 ± 2.353, p < 0.001 for Per), demonstrating that the cholesterol polyps were smaller and more regular in terms of morphology. The classification accuracy, sensitivity, specificity, and area under the curve values were 0.875, 0.885, 0.857, and 0.898, respectively. Conclusions: Ultrasound radiomic analysis based on the spatial and morphological features extracted from ultrasound images effectively contributed to the preoperative diagnosis of true and pseudo gallbladder polyps and may be valuable in their clinical management.