Background: Acute ischemic stroke is one of the most important factors leading to disability and death with the characterization of accumulated neuron death and injured supportive neurovascular structures. Raf-1 kinase inhibitory protein (RKIP) is a key molecule in cell response to survival or death stimuli. However, the role of RKIP in stroke is worthy to be further studied. Methods: We used lentivirus mediated RKIP knockdown and overexpression to investigate the effect of RKIP on animal models of focal cerebral ischemia. Cell Counting Kit-8 assay, lactate dehydrogenase release analysis, and Annexin V-APC apoptosis assay were used to detect the effect RKIP on microglial cell apoptosis and survival. Transwell migration assay was carried out to evaluate the migration of microglia cells. The releases of inflammatory cytokines were determined by ELISA. The activation of NF-kappaB signaling pathway was determined by western blot. Results: Overexpression of RKIP reduced focal cerebral ischemia injury. RKIP knockdown and overexpression regulated survival, activation, and motility via the NF-κB pathway. NF-κB inhibitor BAY 11-7082 blocked the changes caused by RKIP down-regulation after oxygen-glucose deprivation (OGD). RKIP overexpression inhibited the upregulation of phosphorylation of NF-κB induced by OGD and cerebral ischemia. Conclusions: The present study showed that RKIP protects against ischemic stroke through inhibition of microglial excessive activation, inhibits its motility, and promotes neuronal survival partly though IKKβ-IκBα-NF-κB signaling axis and indicate that RKIP is a new target for the treatment of ischemic stroke.

To investigate the influence of region of interest (ROI) size on tumor apparent diffusion coefficient (ADC) measurements in pancreatic cancer. The study population consisted of 64 patients with pathologically proved pancreatic ductal adenocarcinomas (PDACs), who underwent preoperative magnetic resonance imaging (MRI) examinations including diffusion-weighted imaging (DWI). The tumor ADCs were measured by two independent readers using six round ROIs with sizes ranging from 20 to 214 mm2 (9 to 97 pixels) in both the six separate measurements. The intra- and inter-observer variabilities were analyzed by using the coefficient of variance (CV), the interclass correlation coefficient (ICC) and Bland-Altman analysis. The mean ADCs measured with the 6 different-sized ROIs were compared using one-way repeated analysis of variance. The sample sizes were calculated by using 80% power and a 5% significance level to detect 10 to 25% changes in ADC measurements. The largest ROI (ROI214) yielded the best intra-observer repeatability (CV, 6.3%; ICC, 0.93) and inter-observer reproducibility (CV, 10.1%; ICC, 0.84). The mean differences in ADC measurements ± limits of agreement between the two readers were (0.06 ± 0.47) × 10−3 mm2 for ROI20, (0.08 ± 0.46) × 10−3 mm2 for ROI46, (0.05 ± 0.37) × 10−3 mm2 for ROI82, (0.07 ± 0.42) × 10−3 mm2 for ROI115, (0.05 ± 0.43) × 10−3 mm2 for ROI152 and (−0.02 ± 0.29) × 10−3 mm2 for ROI214. ROI size had a considerable influence on the ADC measurements of PDACs.

To investigate the associations between the diffusion parameters obtained from multiple-b-values diffusion weighted imaging (DWI) of pancreatic ductal adenocarcinoma (PDAC) and the aggressiveness and local stage prediction, and assess the values of the quantitative parameters for the discrimination of tumors from healthy pancreas. Fifty-one patients with surgical pathology-proven PDAC (size, 35 ± 12 mm) and fifty-seven healthy volunteers were enrolled. Diffusion parameters including monoexponential apparent diffusion coefficient (ADCb and ADCtotal) and biexponential intravoxel incoherent motion (IVIM) parameters (ADCslow, ADCfast and f) based on 9 b-values (0 to 1000s/mm2) DWI were calculated for the lesions and the healthy pancreas. These parameters were compared by grades of differentiation, lymph node status, tumor stage and location. The diagnostic performances were calculated and compared by using the receiver operating characteristic curves (ROC) analyses. There was no statistically significant difference in ADCb, ADCtotal, ADCslow, ADCfast or f between PDAC stage T1/T2 and stage T3/T4 or moderately differentiated versus poorly differentiated PDAC (p = 0.060-0.941). In addition, no significant differences were observed for the quantitative parameters between tumors located in the pancreatic head versus other pancreatic regions (p = 0.203-0.954) or between tumors with and without metastatic peri-pancreatic lymph nodes (p = 0.313-0.917). ADC25-600, ADC1000, ADCtotal and ADCfast were significantly lower for PDAC compared the healthy pancreas (all p < 0.05). ROC analyses showed the area under curve for ADC20 was the largest (0.911) to distinguish PDAC from normal pancreas (cut-off value, 5.58 × 10−3mm2/s) and had the highest combined sensitivity (89.5%) and specificity (82.4%). Multiple-b-values DWI derived monoexponential and biexponential parameters of PDAC do not exhibit significance dependence on tumor grade or tumor characteristics. ADC20 provided the best accuracy for differentiating PDAC from healthy pancreas in the study.

To determine the effect of region of interest (ROI) on tumor’s apparent diffusion coefficient (ADC) and interobserver variability in thyroid nodules. Thirty-three individuals with 45 pathologically-confirmed thyroid nodules were assessed by preoperative diffusion-weighted imaging (DWI) with b values of 0 and 400 s/mm2, respectively. Two readers evaluated the ADC values of lesions based on three ROI techniques: whole-volume, single-slice and small solid-sample groups. Interobserver variability was analyzed for all ROI techniques, and the mean ADCs of benign and cancerous thyroid nodules were compared. For the mean ADCs of non-cancerous thyroid nodules, average differences and limits of agreement (LOAs) between readers were 0.00 [− 0.17–0.17] × 10− 3 mm2/s for whole-volume ROI (ICC = 0.967), 0.00 [− 0.26–0.26] × 10− 3 mm2/s for single-slice ROI (ICC = 0.932) and − 0.02 [− 0.38–0.41] × 10− 3 mm2/s for small solid-sample ROI (ICC = 0.823). For the mean ADCs of cancerous thyroid nodules, average differences and LOAs between readers were − 0.05 [− 0.23–0.13] × 10− 3 mm2/s (ICC = 0.885), 0.01 [− 0.23–0.25] × 10− 3 mm2/s (ICC = 0.839) and − 0.07 [− 0.52–0.39] × 10− 3 mm2/s (ICC = 0.579) for the three ROI methods, respectively. The mean ADC values were more scattered in the small solid-sample ROI group in comparison with the whole-volume and single-slice groups, in noncancerous and cancerous specimens. Of all three ROI techniques, whole-volume ROI-determined ADC had the highest combined sensitivity (80.0%), specificity (88.3%) and Youden index (0.683), with a cut-off of 1.84 × 10− 3 mm2/s. The ROI method overtly affects ADC measurements in benign and cancerous thyroid nodules. Small solid-sample ROI yielded the worst interobserver variability of average ADC measurements.