Beyond antioxidation: Harnessing the CeO2 nanoparticles as a renoprotective contrast agent for in vivo spectral CT angiography.

It is a challenging task to develop a contrast agent that not only provides excellent image contrast but also protects impaired kidneys from oxidative-related stress during angiography. Clinically approved iodinated CT contrast media are associated with potential renal toxicity, making it necessary to develop a renoprotective contrast agent. Here, we develop a CeO2 nanoparticles (NPs)-mediated three-in-one renoprotective imaging strategy, namely, i) renal clearable CeO2 NPs serve as a one-stone-two-birds antioxidative contrast agent, ii) low contrast media dose, and iii) spectral CT, for in vivo CT angiography (CTA). Benefiting from the merits of advanced sensitivity of spectral CT and K-edge energy of Cerium (Ce, 40.4 keV), an improved image quality of in vivo CTA is successfully achieved with a 10 times reduction of contrast agent dosage. In parallel, the sizes of CeO2 NPs and broad catalytic activities are suitable to be filtered via glomerulus thus directly alleviating the oxidative stress and the accompanying inflammatory injury of the kidney tubules. In addition, the low dosage of CeO2 NPs reduces the hypoperfusion stress of renal tubules induced by concentrated contrast agents used in angiography. This three-in-one renoprotective imaging strategy helps prevent kidney injury from being worsened during the CTA examination.

Stachydrine exhibits a novel antiplatelet property and ameliorates platelet-mediated thrombo-inflammation.

BACKGROUND: Platelets are versatile anucleate cells involved in thrombosis as well as inflammation. Stachydrine (STA), a major bioactive compound extracted from Motherwort, has multiple pharmacological properties. Nevertheless, the significance of STA in platelet regulation and whether STA could ameliorate platelet-mediated thrombo-inflammation still remain elusive. METHODS: Human platelets were used to assess the regulatory effects of STA on platelet activation and interactions with neutrophils in vitro. FeCl3 injury-induced carotid/mesenteric thrombosis and collagen/epinephrine-induced pulmonary thromboembolism model were used to explore whether STA could regulate thrombosis in vivo. Furthermore, a cecal ligation and puncture-induced sepsis model was employed to investigate the role of STA in thrombo-inflammatory diseases. RESULTS: STA markedly suppressed platelet activation represented by aggregation, secretion, αIIbß3-mediated signaling events and calcium mobilization, etc. by inhibiting agonists-induced activation signaling and potentiating cGMP-dependent inhibitory signaling. Mice receiving STA-treated platelets were less susceptible to thrombosis in vivo. In addition, decreased platelet-neutrophil interactions including platelet-neutrophil aggregates and neutrophil extracellular traps, and alleviative sepsis-induced multiorgan damage were observed due to STA-mediated platelet inhibition. CONCLUSION: This study suggested the potential therapeutic role of STA in thrombotic and thrombo-inflammatory disorders.

Diffuse Large B-Cell Lymphoma Promotes Endothelial-to-Mesenchymal Transition via WNT10A/Beta-Catenin/Snail Signaling.

Diffuse large B-cell lymphoma (DLBCL) is one type of highly heterogeneous lymphoid malignancy with 30%~40% of patients experiencing treatment failure. Novel risk stratification and therapeutic approaches for DLBCL are urgently needed. Endothelial-to-mesenchymal transition (EndMT), which contributes to tumor angiogenesis, metastasis, drug resistance, and cancer-associated fibroblast generation, has been detected in the microenvironment of many types of cancers. However, the existence of EndMT in the hematological malignancies microenvironment remains unknown. Here, we identified the existence of EndMT in DLBCL-associated endothelial cells and the clinical relevance of EndMT markers in DLBCL, which was associated with advanced clinical stage and poor prognosis. In vitro experiments confirmed that DLBCL cells stimulated angiogenesis and EndMT of human umbilical vein endothelial cells (HUVECs). We further unveiled the molecular mechanisms underlying this process. We demonstrated that WNT10A, a WNT family member overexpressed in DLBCL tissues and correlated with clinical features in DLBCL, promoted EndMT through glycogen synthase kinase 3ß (GSK3ß)/ß-catenin/snail signaling. WNT10A inhibited the binding of GSK3ß to ß-catenin/snail, resulting in ß-catenin and snail nuclear accumulation and target gene transcription. Silencing ß-catenin and snail respectively attenuated WNT10A-induced angiogenesis and EndMT. The interplay between ß-catenin-dependent and snail-dependent signaling was also confirmed in this study. Collectively, these findings identified that WNT10A/GSK3ß/ß-catenin/snail pathway performed vital roles in DLBCL-induced EndMT and indicated that EndMT markers and WNT10A may serve as novel predictors of clinical outcome.

A logistic regression model for prediction of glioma grading based on radiomics. / 基于影像组学的logistic回归模型预测胶质瘤分级.

OBJECTIVES: Glioma is the most common intracranial primary tumor in central nervous system. Glioma grading possesses important guiding significance for the selection of clinical treatment and follow-up plan, and the assessment of prognosis. This study aims to explore the feasibility of logistic regression model based on radiomics to predict glioma grading. METHODS: Retrospective analysis was performed on 146 glioma patients with confirmed pathological diagnosis from January, 2012 to December, 2018. A total of 41 radiomics features were extracted from contrast-enhanced T1-weighted imaging (T1WI+C) lesion by manual segmentation. Least absolute shrinkage and selection operator (LASSO) was used to select the most-predictive radiomics features for pathological grading and to calculate radiomics score (Rad-score) of each patient. A logistic regression model was built to explore the correlation between giloma grading and Rad-score. Receiver operating characteristic (ROC) curve was performed to evaluate the model's predictive ability with area under the curve (AUC) for the evaluation index. Hosmer-Lemeshow test was used to measure the model's predictive accuracy. RESULTS: A total of 5 imaging features selected by LASSO were used to establish a logistic regression model for predicting glioma grading. The model showed good discrimination with AUC value of 0.919. Hosmer-Lemeshow test showed no significant difference between the calibration curve and the ideal curve (P=0.808), indicating high predictive accuracy of the model. CONCLUSIONS: The logistic regression model using radiomics exhibits a relatively high accuracy for predicting glioma grading, which may serve as a complementary tool for preoperative prediction of giloma grading.

[Clinical features and C12orf65 mutations of autosomal recessive spastic paraplegia-55: a case report].

This article reports the clinical features and C12orf65 gene mutations of a girl with autosomal recessive spastic paraplegia-55. The 8-year-old girl experienced disease onset at the age of 5 years and had optic atrophy as the main clinical manifestation, with slow movements in standing up and a slight duck-shaped gait. Peripheral blood DNA samples were collected from this child and her parents and brother to perform high-throughput whole-exome sequencing and high-throughput mitochondrial genome sequencing. Sanger sequencing was performed for verification. The results showed two compound heterozygous mutations, c.394C>T and c.447_449delGGAinsGT, in the C12orf65 gene. The former mutation came from her father and was a known pathogenic mutation, and the latter came from her mother and was a novel mutation which had not been reported in literature. This study expands the mutation spectrum of the C12orf65 gene and thus provides a molecular basis for the etiological diagnosis of the child and the genetic counseling of the family.

Bi-DTPA as a high-performance CT contrast agent for in vivo imaging.

Clinically used iodinated computer tomography (CT) contrast agents suffer from low sensitivity, and the emerging lanthanide-chelates and CT imaging nanoagents raise great safety concerns. The fusion of high sensitivity and good biocompatibility is highly desired for the development of CT contrast agents. Herein, we propose a facile and green one-pot synthesis strategy for the fabrication of a small molecular CT contrast agent, Bi-diethylene triamine pentaacetate acid (DTPA) complex, for high-performance CT and spectral CT imaging. The Bi-DTPA exhibits yield of near 100%, outstanding water solubility, favorable biocompatibility, large-scale production capability, and superior X-ray attenuation ability, and is successfully applied in high-quality in vivo kidney imaging and gastrointestinal tract CT imaging and appealing spectral CT imaging. The proposed contrast agent can be rapidly excreted from body, avoiding the potential side effects caused by the long-term retention in vivo. Furthermore, our design shows great potential in developing diverse multifunctional contrast agents via chemical modification. The proposed Bi-DTPA with unique superiorities shows a bright prospect in clinic CT imaging, especially spectral CT imaging, and lays down a new way for the design of high-performance CT contrast agents with great clinical transformation potential.

Resting-state fMRI in primary Sjögren syndrome.

Background The involvement of the central nervous system in primary Sjögren syndrome (pSS) remains controversial. Functional magnetic resonance imaging (fMRI) is a relatively new method that can be applied to investigate the heterogeneity of central nervous system (CNS) involvement in pSS patients through regional homogeneity (ReHo) analysis. Purpose To collect data from pSS patients and healthy controls, and use ReHo analysis to elucidate the neurobiological mechanism of CNS involvement in pSS. Material and Methods Fourteen clinically diagnosed pSS patients and 14 age- and gender-matched healthy controls underwent resting-state fMRI. The data were processed by ReHo analysis. The double sample t-test was used to compare ReHo data between groups. Results Compared to controls, pSS patients had significantly increased ReHo values in the right cerebrum, left limbic lobe, right middle temporal gyrus, and the inferior parietal lobe. However, ReHo values significantly decreased in the right lingual gyrus, left cuneiform lobe, left superior occipital gyrus, bilateral middle occipital gyrus, and the fronto-parietal junction area ( P < 0.01, clusters ≥ 50 voxels). Conclusion This study demonstrates the abnormal brain activity in the visual cortex and fronto-parietal junction area in pSS patients, suggesting pathological neuronal dysfunction in these regions.

Analysis of brain and spinal cord lesions to occult brain damage in seropositive and seronegative neuromyelitis optica.

OBJECTIVES: According to aquaporin-4 antibody (AQP4-Ab), neuromyelitis optica (NMO) can be divided into seropositive and seronegative subgroups. The purpose of this study was to a) compare the distribution of spinal cord and brain magnetic resonance imaging (MRI) lesions between seropositive and seronegative NMO patients; b) explore occult brain damage in seropositive and seronegative NMO patients; and c) explore the contribution of visible lesions to occult grey and white matter damage in seropositive and seronegative NMO patients. MATERIALS AND METHODS: Twenty-two AQP4-Ab seropositive and 14 seronegative NMO patients and 30 healthy controls were included in the study. Two neuroradiologists independently measured the brain lesion volume (BLV) and the length of spinal cord lesion (LSCL) and recorded the region of brain lesions. The normal-appearing grey matter volume (NAGM-GMV) and white matter fractional anisotropy (NAWM-FA) were calculated for each subject to evaluate occult brain damage. RESULTS: The seropositive patients displayed more extensive damage in the spinal cord than the seronegative patients, and the seronegative group had a higher proportion of patients with brainstem lesions (28.57%) than the seropositive group (4.55%, P=0.064). Both NMO subgroups exhibited reduced NAGM-GMV and NAWM-FA compared with the healthy controls. NAGM-GMV was negatively correlated with LSCL in the seropositive group (rs=-0.444, P=0.044) and with BLV in the seronegative group (rs=-0.768, P=0.002). NAWM-FA was also negatively correlated with BLV in the seropositive group (rs=-0.682, P<0.001). CONCLUSION: Our findings suggest that the occult brain damage in these two NMO subgroups may be due to different mechanisms, which need to be further clarified.

Subregional structural and connectivity damage in the visual cortex in neuromyelitis optica.

Patients with neuromyelitis optica (NMO) have shown structural and functional impairments in the visual cortex. We aimed to characterize subregional grey matter volume (GMV) and resting-state functional connectivity (rsFC) changes in the visual cortex in NMO. Thirty-seven NMO patients and forty-two controls underwent structural and functional MRI scans. The GMV and rsFC of each visual subregion were compared between the groups. Compared with controls, NMO patients had GMV reductions in the bilateral V1, V2, V3d, VP, and LO and in the left V3A. In canonical visual pathways, the relatively low-level subregions showed more significant GMV reductions than did the high-level ones. Regardless of GMV correction, NMO patients showed reduced rsFC in the bilateral LO and V4v and in the left V2. The GMVs of the bilateral V1 and LO and of the left V2 and V3d were negatively correlated with clinical disability in NMO patients; these correlation coefficients were associated with hierarchical positions in the visual pathways. These findings suggest that in NMO, the low-level visual subregions have more severe structural damage; structural damage is not the only factor affecting rsFC alterations of visual subregions; GMV reduction in the low-level visual subregions has the highest predictive value for clinical disability.