Notch Signaling Regulates Microglial Activation and Inflammatory Reactions in a Rat Model of Temporal Lobe Epilepsy.

The inflammatory response mediated by microglia in the central nervous system is closely related to epilepsy. Notch signaling plays an important role in the microglial activation during hypoxia. This study aimed to investigate whether Notch signaling is involved in microglial activation and subsequent inflammation-related neuronal injury during the process of epileptogenesis in a rat model of temporal lobe epilepsy. By using western blotting, real-time quantitative PCR, immunohistochemistry and immunofluorescence labeling, we found that the expression of Notch signaling increased after status epilepticus and that a γ-secretase inhibitor could significantly inhibit the upregulation of Notch signaling, the activation of microglia, and the release of proinflammatory cytokines. Likewise, the neuronal apoptosis and loss in the hippocampus after SE were attenuated by the γ-secretase inhibitor. These results suggest that Notch signaling plays a key role in neuroinflammation and inflammation-related neuronal damage in epilepsy, and γ-secretase inhibitors may become a novel prospective therapeutic agent for epilepsy.

Clot Meniscus Sign Is Associated With Thrombus Permeability and Choice of Mechanical Thrombectomy Technique in Acute Middle Cerebral Artery Occlusion.

Background and Purpose: The method of mechanical thrombectomy (MT) is related to vascular anatomy and stroke etiology. Meniscus sign and thrombus permeability as imaging markers may be instructive for the selection of MT. This study aims to clarify the relationship among meniscus sign, thrombus permeability, and choice of MT in patients with acute middle cerebral artery occlusion. Materials and Methods: A total of 111 patients with acute middle cerebral artery occlusion (MCAO) who underwent MT were retrospectively analyzed. Clot meniscus sign was defined as the appearance of meniscoid/edge-like or single- or double-wall contrast channels besides or around insular blood clots. The radiographic, clinical, and surgical data of patients with MCAO with or without meniscus sign were compared. Results: The meniscus sign positive group (n = 26) has higher thrombus permeability (HUs) (26.92 ± 9.69 vs. 22.84 ± 7.88, p = 0.031) than those without it. Shorter puncture-to-recanalization (P2R) time (65.5 vs. 88, p = 0.012), higher complete recanalization rate (85.71 vs. 33.33%, p < 0.01), and better clinical outcome (p < 0.01) were obtained by selecting contact aspiration (CA) over stent retriever (SR) in patients with positive meniscus sign. In patients with negative meniscus sign, there was no significant difference in clinical outcome after receiving CA or SR. Conclusion: Patients with MCAO with positive meniscus sign have higher thrombus permeability and are more suitable for CA to acquire better clinical outcomes.

Thin-Section Chest CT Imaging of COVID-19 Pneumonia: A Comparison Between Patients with Mild and Severe Disease.

PURPOSE: To compare radiologic characteristics of coronavirus disease 2019 (COVID-19) pneumonia at thin-section CT on admission between patients with mild and severe disease. MATERIALS AND METHODS: Seventy patients with COVID-19 pneumonia who were admitted to Zhongnan Hospital of Wuhan University between January 20, 2020 and January 27, 2020 were enrolled. On the basis of the World Health Organization guidelines, 50 patients were categorized with the mild form and 20 with the severe form based on clinical conditions. Imaging features, clinical, and laboratory data were reviewed and compared. RESULTS: Patients with the severe form (median age, 65 years; interquartile range [IQR]: 54.75-75.00 years) were older than those with the mild form of disease (median age, 42.5 years; IQR: 32.75-58.50 years) (P < .001). Patients with the severe form of disease had more lung segments involved (median number of segments: 17.5 vs 7.5, P ≤ .001) and also larger opacities (median number of segments with opacities measuring 3 cm to less than 50% of the lung segment: 5.5 vs 2.0, P = .006; ≥ 50% of lung segment: 7.5 vs 0.0, P < .001). They also had more interlobular septal thickening (75% vs 28%, P < .001), higher prevalence of air bronchograms (70% vs 32%, P = .004), and pleural effusions (40% vs 14%, P = .017). CONCLUSION: Ground-glass opacities with or without consolidation in a peripheral and basilar predominant distribution were the most common findings in COVID-19 pneumonia. Patients with the severe form of the disease had more extensive opacification of the lung parenchyma than did patients with mild disease. Interlobular septal thickening, air bronchograms, and pleural effusions were also more prevalent in severe COVID-19.© RSNA, 2020.

Analysis of the Risk Factors for Mortality in Adult COVID-19 Patients in Wuhan: A Multicenter Study.

Objectives: An outbreak of coronavirus disease (COVID-19) in 2019 in Wuhan, China, has spread quickly worldwide. However, the risk factors associated with COVID-19-related mortality remain controversial. Methods: A total of 245 adult patients with laboratory-confirmed COVID-19 from two centers were analyzed. Chi-square, Fisher's exact, and the Mann-Whitney U-tests were used to compare the clinical characteristics between the survivors and non-survivors. To explore the risk factors associated with in-hospital death, univariable and multivariable cox regression analyses were used. Results: Of the 245 patients included in this study, 23 (9.4%) died in the hospital. The multivariate regression analysis showed increased odds of in-hospital deaths associated with age, D-dimer levels >1,000 ng/L, platelet count <125, and higher serum creatinine levels. Conclusions: We identified risk factors that show significant association with mortality in adult COVID-19 patients, and our findings provide valuable references for clinicians to identify high-risk patients with COVID-19 at an early stage.

HIF-1α is Critical for the Activation of Notch Signaling in Neurogenesis During Acute Epilepsy.

Emerging evidence suggests that hypoxia-inducible factors (specifically, HIF-1α) and Notch signaling are involved in epileptogenesis and that cross-coupling exists between HIF-1α and Notch signaling in other diseases, including tumors and ischemia. However, the exact molecular mechanisms by which HIF-1α and Notch signaling affect the development of epilepsy, especially regarding neurogenesis, remain unclear. In the present study, we investigated the role of HIF-1α in neurogenesis and whether Notch signaling is involved in this process during epileptogenesis by assessing hippocampal apoptosis, neuronal injury, and the proliferation and differentiation of neural stem cells (NSCs) in four groups, including control, epilepsy, epilepsy+2-methoxyestradiol (2ME2) and epilepsy+GSI-IX (DAPT) groups. Our data demonstrated that HIF-1α mediated neurogenesis during acute epilepsy, which required the participation of Notch signaling. The immunoprecipitation data illustrated that HIF-1α activated Notch signaling by physically interacting with the Notch intracellular domain (NICD) in epilepsy. In conclusion, our results suggested that HIF-1α-Notch signaling enhanced neurogenesis in acute epilepsy and that neurogenesis during epileptogenesis was reduced once this pathway was blocked; thus, members of this pathway might be potential therapeutic targets for epilepsy.

The diagnostic performance of perfusion MRI for differentiating glioma recurrence from pseudoprogression: A meta-analysis.

BACKGROUND: The purpose of this meta-analysis was to evaluate the diagnostic accuracy of perfusion magnetic resonance imaging (MRI) as a method for differentiating glioma recurrence from pseudoprogression. METHODS: The PubMed, Embase, Cochrane Library, and Chinese Biomedical databases were searched comprehensively for relevant studies up to August 3, 2016 according to specific inclusion and exclusion criteria. The quality of the included studies was assessed according to the quality assessment of diagnostic accuracy studies (QUADAS-2). After performing heterogeneity and threshold effect tests, pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated. Publication bias was evaluated visually by a funnel plot and quantitatively using Deek funnel plot asymmetry test. The area under the summary receiver operating characteristic curve was calculated to demonstrate the diagnostic performance of perfusion MRI. RESULTS: Eleven studies covering 416 patients and 418 lesions were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.88 (95% confidence interval [CI] 0.84-0.92), 0.77 (95% CI 0.69-0.84), 3.93 (95% CI 2.83-5.46), 0.16 (95% CI 0.11-0.22), and 27.17 (95% CI 14.96-49.35), respectively. The area under the summary receiver operating characteristic curve was 0.8899. There was no notable publication bias. Sensitivity analysis showed that the meta-analysis results were stable and credible. CONCLUSION: While perfusion MRI is not the ideal diagnostic method for differentiating glioma recurrence from pseudoprogression, it could improve diagnostic accuracy. Therefore, further research on combining perfusion MRI with other imaging modalities is warranted.

Characterization of long noncoding RNA and messenger RNA signatures in melanoma tumorigenesis and metastasis.

The incidence of melanoma, the most aggressive and life-threatening form of skin cancer, has significantly risen over recent decades. Therefore, it is essential to identify the mechanisms that underlie melanoma tumorigenesis and metastasis and to explore novel and effective melanoma treatment strategies. Accumulating evidence s uggests that aberrantly expressed long noncoding RNAs (lncRNAs) have vital functions in multiple cancers. However, lncRNA functions in melanoma tumorigenesis and metastasis remain unclear. In this study, we investigated lncRNA and messenger RNA (mRNA) expression profiles in primary melanomas, metastatic melanomas and normal skin samples from the Gene Expression Omnibus database. We used GSE15605 as the training set (n = 74) and GSE7553 as the validation set (n = 58). In three comparisons (primary melanoma versus normal skin, metastatic melanoma versus normal skin, and metastatic melanoma versus primary melanoma), 178, 295 and 48 lncRNAs and 847, 1758, and 295 mRNAs were aberrantly expressed, respectively. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses to examine the differentially expressed mRNAs, and potential core lncRNAs were predicted by lncRNA-mRNA co-expression networks. Based on our results, 15 lncRNAs and 144 mRNAs were significantly associated with melanoma tumorigenesis and metastasis. A subsequent analysis suggested a critical role for a five-lncRNA signature during melanoma tumorigenesis and metastasis. Low expression of U47924.27 was significantly associated with decreased survival of patients with melanoma. To the best of our knowledge, this study is the first to explore the expression patterns of lncRNAs and mRNAs during melanoma tumorigenesis and metastasis by re-annotating microarray data from the Gene Expression Omnibus (GEO) microarray dataset. These findings reveal potential roles for lncRNAs during melanoma tumorigenesis and metastasis and provide a rich candidate reservoir for future studies.

Correction: Characterization of long noncoding RNA and messenger RNA signatures in melanoma tumorigenesis and metastasis.

[This corrects the article DOI: 10.1371/journal.pone.0172498.].

Trifunctional Polymeric Nanocomposites Incorporated with Fe3O4/Iodine-Containing Rare Earth Complex for Computed X-ray Tomography, Magnetic Resonance, and Optical Imaging.

In this study, a novel polymerizable CT contrast agent integrating iodine with europium(III) has been developed by a facile and universal coordination chemistry method. The Fe3O4 nanoparticles are then incorporated into this iodine-containing europium complex by seed-emulsifier-free polymerization. The nanocomposites combining the difunctional complex and superparamagnetic Fe3O4 nanoparticles, which have uniform size dispersion and high encapsulation rate, are suitable for computed X-ray tomography (CT), magnetic resonance imaging (MRI), and optical imaging. They possess good paramagnetic properties with a maximum saturation magnetization of 2.16 emu/g and a transverse relaxivity rate of 260 mM(-1) s(-1), and they exhibit obvious contrast effects with an iodine payload less than 4.8 mg I/mL. In the in vivo optical imaging assessment, vivid fluorescent dots can be observed in the liver and spleen by two-photon confocal scanning laser microscopy (CLSM). All the results showed that nanocomposites as polymeric trifunctional contrast agents have great clinical potential in CT, MR, and optical imaging.