Objective: To investigate the levels of glutathione transferase (GST), a protective enzyme against aldehydes, and especially 4-hydroxynonenal (HNE) in the brain and ventricular CSF of autopsied AD and normal control subjects. Background: Studies have implicated increased levels of oxidative stress in the brain in the pathogenesis of AD. Decreased levels of polyunsaturated fatty acids and increased levels of markers of lipid peroxidation have been reported in the brain in AD, particularly in areas severely affected in the disease. HNE, one marker of lipid peroxidation, is neurotoxic in neuronal culture and in vivo and is elevated in AD brain and CSF. Methods: We measured levels of GST activity and protein in multiple brain regions and ventricular CSF in short-postmortem-interval AD patients and age-matched prospectively evaluated control subjects. Results: A decrease in GST activity in all brain areas was observed in AD compared with controls with significant decreases in the amygdala, hippocampus and parahippocampal gyrus, inferior parietal lobule, and nucleus basalis of Meynert. Levels of GST protein also were depleted in most brain regions in AD. A significant decrease in GST activity and protein levels was also found in ventricular CSF in AD. Conclusion: Reduced levels of GST, a protective mechanism against HNE, may have a role in the pathogenesis of neuron degeneration in AD.

Compared with qualitative assessment of conventional CT imaging features, quantitative assessment of gemstone spectral imaging parameters, especially the combination of venous phase slope of the spectral Hounsfield unit curve and arterial phase normalized iodine concentration, showed higher accuracy for the preoperative diagnosis of metastasis to the cervical lymph nodes in patients with papillary thyroid cancer. PurposeTo evaluate the use of dual-energy spectral computed tomographic (CT) quantitative parameters compared with the use of conventional CT imaging features for preoperative diagnosis of metastasis to the cervical lymph nodes in patients with papillary thyroid cancer.Materials and MethodsThis study was approved by the ethics committee and all patients provided written informed consent. Analyses of quantitative gemstone spectral imaging data and qualitative conventional CT imaging features were independently performed by different groups of radiologists. Excised lymph nodes were located and labeled during surgery according to location on preoperative CT images and were evaluated histopathologically. Single and combined parameters were fitted to simple and multiple logistic regression models, respectively, by means of the generalized estimating equations method. Sensitivity and specificity analyses were performed by using receiver operating characteristic curves and were compared with data from the qualit...

Background: Previous studies have indicated that quantitative MRI (qMR) is beneficial for diagnosis of breast cancer. As a novel qMR technology, synthetic MRI (syMRI) may be advantageous by offering simultaneous generation of T1 and T2 mapping in one scan within a few minutes and without concern to the deposition of the gadolinium contrast agent in cell nucleus. In this study, the potential of quantitative mapping derived from Synthetic MRI (SyMRI) to diagnose breast cancer was investigated. Methods: From April 2018 to May 2019, a total of 87 patients with suspicious breast lesions underwent both conventional and SyMRI before treatment. The quantitative metrics derived from SyMRI, including T1 and T2 values, were measured in breast lesions. The diagnostic performance of SyMRI was evaluated with unpaired Student’s t-tests, receiver operating characteristic curve analysis and multivariate logistic regression analysis. The AUCs of quantitative values were compared using Delong test. Results: Among 77 patients who met the inclusion criteria, 48 were diagnosed with histopathological confirmed breast cancers, and the rest had benign lesions. The breast cancers showed significantly higher T1 (1611.61 ± 215.88 ms) values and lower T2 (80.93 ± 7.51 ms) values than benign lesions. The area under the ROC curve (AUC) values were 0.931 (95% CI: 0.874–0.989) and 0.883 (95% CI: 0.810–0.956) for T1 and T2 maps, respectively, in diagnostic discrimination between breast cancers and benign lesions. A slightly increased AUC of 0.978 (95% CI: 0.915–0.993) was achieved by combining those two relaxation-based quantitative metrics. Conclusion: In conclusion, our preliminary study showed that the quantitative T1 and T2 values obtained by SyMRI could distinguish effectively between benign and malignant breast lesions, and T1 relaxation time showed the highest diagnostic efficiency. Furthermore, combining the two quantitative relaxation metrics further improved their diagnostic performance.

Accurate detection is essential for brain metastasis (BM) management, but manual identification is laborious. This study developed, validated, and evaluated a BM detection (BMD) system. Five hundred seventy-three consecutive patients (10 448 lesions) with newly diagnosed BMs and 377 patients without BMs were retrospectively enrolled to develop a multi-scale cascaded convolutional network using 3D-enhanced T1-weighted MR images. BMD was validated using a prospective validation set comprising an internal set (46 patients with 349 lesions; 44 patients without BMs) and three external sets (102 patients with 717 lesions; 108 patients without BMs). The lesion-based detection sensitivity and the number of false positives (FPs) per patient were analyzed. The detection sensitivity and reading time of three trainees and three experienced radiologists from three hospitals were evaluated using the validation set. The detection sensitivity and FPs were 95.8% and 0.39 in the test set, 96.0% and 0.27 in the internal validation set, and ranged from 88.9% to 95.5% and 0.29 to 0.66 in the external sets. The BMD system achieved higher detection sensitivity (93.2% [95% CI, 91.6–94.7%]) than all radiologists without BMD (ranging from 68.5% [95% CI, 65.7–71.3%] to 80.4% [95% CI, 78.0–82.8%], all P < .001). Radiologist detection sensitivity improved with BMD, reaching 92.7% to 95.0%. The mean reading time was reduced by 47% for trainees and 32% for experienced radiologists assisted by BMD relative to that without BMD. BMD enables accurate BM detection. Reading with BMD improves radiologists’ detection sensitivity and reduces their reading times.

Background: Cisplatin (CDDP) is the first-line chemotherapeutic strategy to treat patients with ovarian cancer (OC). The development of CDDP resistance remains an unsurmountable obstacle in OC treatment and frequently induces tumor recurrence. Circular RNAs (circRNAs) are noncoding RNAs with important functions in cancer progression. Whether circRNAs function in CDDP resistance of OC is unclear. Methods: Platinum-resistant circRNAs were screened via circRNA deep sequencing and examined using in situ hybridization (ISH) in OC. The role of circPLPP4 in CDDP resistance was assessed by clone formation and Annexin V assays in vitro, and by OC patient-derived xenografts and intraperitoneal tumor models in vivo. The mechanism underlying circPLPP4-mediated activation of miR-136/PIK3R1 signaling was examined by luciferase reporter assay, RNA pull-down, RIP, MeRIP and ISH. Results: circPLPP4 was remarkably upregulated in platinum resistant OC. circPLPP4 overexpression significantly enhanced, whereas circPLPP4 silencing reduced, OC cell chemoresistance. Mechanistically, circPLPP4 acts as a microRNA sponge to sequester miR-136, thus competitively upregulating PIK3R1 expression and conferring CDDP resistance. The increased circPLPP4 level in CDDP-resistant cells was caused by increased RNA stability, mediated by increased N6-methyladenosine (m⁶A) modification of circPLPP4. In vivo delivery of an antisense oligonucleotide targeting circPLPP4 significantly enhanced CDDP efficacy in a tumor model. Conclusions: Our study reveals a plausible mechanism by which the m⁶A -induced circPLPP4/ miR-136/ PIK3R1 axis mediated CDDP resistance in OC, suggesting that circPLPP4 may serve as a promising therapeutic target against CDDP resistant OC. A circPLPP4-targeted drug in combination with CDDP might represent a rational regimen in OC.

To evaluate the diagnostic value of diffusion-weighted MRI for differentiating metastatic from non-metastatic retropharyngeal lymph nodes (RLNs) in patients with nasopharyngeal carcinoma (NPC). Untreated patients with NPC (n = 145) were scanned with both morphological MRI and diffusion-weighted imaging (DWI). RLNs (n = 335) were classified as metastatic on the basis of response to therapy as assessed on follow-up MRI. Morphological (short- and long-axial diameters) and functional [mean apparent diffusion coefficient (ADC) and minimum ADC values] parameters of the RLNs were derived from DWI and compared between metastatic and non-metastatic groups. A receiver operating characteristic curve and the area under the curve were used to evaluate the effectiveness of individual criteria and to generate threshold values to diagnose RLN metastases. Statistically significant differences between metastatic and non-metastatic RLNs were found for all four parameters derived from DWI (p < 0.001). At threshold values, accuracies of the ADC-based criteria (0.938 and 0.965 for mean and minimum ADC values, respectively) were greater than that of size-based criteria (0.838 and 0.809 for short- and long-axial diameters). The minimum ADC value at the threshold of 0.89 × 10(-3) mm(2) s(-1) was the most effective of all parameters in differentiating metastatic from non-metastatic RLNs with the sensitivity of 95.7%, specificity of 95.1% and accuracy of 96.5%. DWI is feasible for differentiating metastatic RLNs from non-metastatic nodes in patients with NPC with high accuracy, and the minimum ADC derived from DWI could serve as a standard clinical marker for disease status.