Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation.

Glioblastoma (GBM) is a lethal cancer characterized by hypervascularity and necrosis associated with hypoxia. Here, it is found that hypoxia preferentially induces the actin-binding protein, Transgelin (TAGLN), in GBM stem cells (GSCs). Mechanistically, TAGLN regulates HIF1α transcription and stabilizes HDAC2 to deacetylate p53 and maintain GSC self-renewal. To translate these findings into preclinical therapeutic paradigm, it is found that sodium valproate (VPA) is a specific inhibitor of TAGLN/HDAC2 function, with augmented efficacy when combined with natural borneol (NB) in vivo. Thus, TAGLN promotes cancer stem cell survival in hypoxia and informs a novel therapeutic paradigm.

Increased Brain Iron Deposition in Episodic Migraine: A Pilot Voxel-based Quantitative Susceptibility Mapping

INTRODUCTION: Although iron deposition has been identified as a significant migraine trigger, the key structures in episodic migraine (EM) remain unknown. OBJECTIVE: The aim of this study is to investigate cerebral iron deposition in EM using an advanced voxel-based quantitative susceptibility mapping (QSM). METHODS: A multi-echo gradient echo sequence MR was performed in 15 episodic migraine patients (EMs) and 27 normal control subjects (NCs). The reconstructed quantitative susceptibility mapping images and voxel-based analysis were performed over the entire brain. The susceptibility value of all brain regions with altered iron deposition was extracted, and the correlations between susceptibility value and clinical variables (including HAMA, HAMD, MoCA, VAS, MIDAS score, diseased duration, and headache frequency) were calculated. RESULTS: EM patients presented increased susceptibility value in the left putamen and bilateral substantia nigra (SN) compared with NC. There was no correlation between susceptibility value and the clinical variables. CONCLUSION: Increased brain iron deposition in the extrapyramidal system may be a biomarker for migraine, and abnormal iron metabolism may be involved in the extrapyramidal mechanism. The QSM technique would be an optimal and simple tool for clinical practice and research in iron measurement.

[Brain iron deposition increases in the bilateral substantia nigra of patients with medication-overuse headache: a quantitative susceptibility mapping analysis].

OBJECTIVE: To investigate iron accumulation level over the whole brain and explore the possible neuromechanism of medication-overuse headache (MOH) using quantitative susceptibility mapping (QSM). METHODS: Thirty-seven MOH patients and 27 normal control subjects were enrolled in the study for examinations with both a multiecho gradient echo magnetic resonance (MR) sequence and brain high resolution structural imaging. A voxel-based analysis was performed to detect the brain regions with altered iron deposition, and the quantitative susceptibility mapping values of the positive brain regions were extracted. Correlation analysis was performed between the susceptibility values and the clinical variables of the patients. RESULTS: In patients with MOH, increased susceptibility values were found mainly in the bilateral substantia nigra (SN) (MNI coordinate: 8, -18, -14; -6, -16, -14) as compared with the normal control subjects (P < 0.001), but these alterations in iron deposition were not significantly correlated with the clinical variables of the patients (P > 0.05). The susceptibility value in the left SN had an area under curve (AUC) of 0.734, and at the cut-off value of 0.077, its diagnostic sensitivity was 72.97% and its specificity was 70.37% for distinguishing MOH from normal controls; The susceptibility value in the right SN had an AUC of 0.699 with a diagnostic sensitivity of 72.97% and a specificity of 62.96% at the cut-off value of 0.084. CONCLUSION: Increased iron deposition occurs in the bilateral SN of MOH patients, which provides a new insight into the mechanism of mesocorticolimbic dopamine system dysfunction in MOH. QSM technique can be used as a non-invasive means for quantitative analysis of brain iron deposition in migraine neuroimaging.

[MRI Findings of the Uterine Tumors Resembling Ovarian Sex Cord Tumors:Report of Two Cases].

Uterine tumors resembling ovarian sex cord tumors are rarely reported with limited imaging findings.The current study reported two case of uterine tumors resembling ovarian sex cord tumors and described the detailed MRI findings,which would provide valuable imaging evidence for the diagnosis of such tumors.

Cofilin Acts as a Booster for Progression of Malignant Tumors Represented by Glioma.

Cofilin, as a depolymerization factor of actin filaments, has been widely studied. Evidences show that cofilin has a role in actin structural reorganization and dynamic regulation. In recent years, several studies have demonstrated a regulatory role for cofilin in the migration and invasion mediated by cell dynamics and epithelial to mesenchymal transition (EMT)/EMT-like process, apoptosis, radiotherapy resistance, immune escape, and transcriptional dysregulation of malignant tumor cells, particularly glioma cells. On this basis, it is practical to evaluate cofilin as a biomarker for predicting tumor metastasis and prognosis. Targeting cofilin regulating kinases, Lin11, Isl-1 and Mec-3 kinases (LIM kinases/LIMKs) and their major upstream molecules inhibits tumor cell migration and invasion and targeting cofilin-mediated mitochondrial pathway induces apoptosis of tumor cells represent effective options for the development of novel anti-malignant tumor drug, especially anti-glioma drugs. This review explores the structure, general biological function, and regulation of cofilin, with an emphasis on the critical functions and prospects for clinical therapeutic applications of cofilin in malignant tumors represented by glioma.

[Atypical Cystic Meningioma:Report of One Case].

The diagnosis of atypical cystic meningioma is difficult because of the atypical MRI findings.This paper reported a case of atypical cystic meningioma and described the detailed MRI findings,which would provide valuable imaging evidence for the localization and classification of cystic meningioma.

Hypoperfusion in nucleus accumbens in chronic migraine using 3D pseudo-continuous arterial spin labeling imaging MRI.

BACKGROUND: Nucleus accumbens (NAcc) played an important role in pain mediation, and presents changes of neuronal plasticity and functional connectivity. However, less is known about altered perfusion of NAcc in chronic migraine (CM). The aim of this study is to investigate the altered perfusion of the NAcc in CM using a MR three-dimensional pseudo-continuous arterial spin labeling (3D PCASL) imaging. METHODS: Thirteen CM patients and 15 normal controls (NC) were enrolled and underwent 3D PCASL and brain structural imaging. The cerebral blood flow (CBF) images were co-registered with the brain structural images, and the volume and CBF value of NAcc were extracted from the raw brain structural images and co-registered CBF images using an individual NAcc mask, which was obtained from the AAL3 template under transformation by the inverse deformation field generated from the segmentation of the brain structural images. The independent sample t test and receiver operating characteristic (ROC) curve was used to investigate the altered volume and perfusion of the NAcc in CM patients. RESULTS: There was no significant difference for the volume of bilateral NAccs between CM and NC (p > 0.05). CM presented a lower CBF value (49.34 ± 6.09 ml/100 mg/min) compared with that of NC (55.83 ± 6.55 ml/100 mg/min) in left NAcc (p = 0.01), while right NAcc showed no significant difference between CM and NC (p = 0.11). ROC analysis identified that the area under the curve was 0.73 (95CI% 0.53-0.88) with cut-off value 48.63 ml/100 mg/min with sensitivity 50.00% and specificity 93.33%. The correlation analysis found a negative correlation between the CBF value of the left NAcc and VAS score (r = -0.61, p = 0.04). CONCLUSION: Hypoperfusion of the left NAcc was observed in CM, which could be considered as a potential diagnostic imaging biomarker in CM.

The increased iron deposition of the gray matter over the whole brain in chronic migraine: An exploratory quantitative susceptibility mapping study.

BACKGROUND: Prior studies identified iron deposition in deep brain nuclei and the periaqueductal gray matter region in chronic migraine, and less is known about the cerebral iron deposition over the whole cerebral gray matter in CM. The aim of this case-control study is to investigate the cerebral iron deposition of gray matter in CM using an advanced quantitative susceptibility mapping. METHODS: A multi-echo gradient echo MR sequence was used to obtain raw quantitative susceptibility mapping data from 12 CM patients and 18 normal controls and the quantitative susceptibility mapping were reconstructed. Three dimensional T1 images were segmented and the gray matter mask was generated to extract the susceptibility value of gray matter over the whole brain. The independent t test and receiver operating characteristic curve Receiver operating characteristics was used to investigate the iron deposition changes in CM patients. RESULTS: CM presented a higher susceptibility value (1.44 × 10-3 ppm) compared with NC group (0.47 × 10-3 ppm) (p < 0.0001) over the whole cerebral gray matter. There was no correlation between susceptibility value and the clinical variables including disease duration, Visual Analog Scale (VAS), Migraine Disability Assessment Scale (MIDAS), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and Montreal Cognitive Assessment (MoCA) scores (p > 0.05). ROC analysis demonstrated the susceptibility had a high diagnostic efficacy (AUC 0.949, sensitivity 77.78% and specificity 100%) in distinguishing CM from NC. CONCLUSION: CM patients had increased iron deposition in total cerebral gray matter which could be considered as a potential diagnostic and evaluated imaging biomarker in CM.

[Papillary Tumor of the Pineal Region:Report of One Case].

We report a case of papillary tumor in the pineal region.The imaging findings mainly included:(1)slight high density on CT images;(2)short T1 signal,cystic changes,and evident enhancement on magnetic resonance imaging.

[Two Cases of Hypovascular Pituitary Metastases and Literature Review].

Pituitary metastasis,a rare kind of intracranial malignant tumor,is characterized by metastasis from all parts of the body to the pituitary.The common tumors metastatic to pituitary are abundant with blood supply,located in the posterior pituitary lobe and/or the pituitary stalk.The lesion shows infiltrative growth,and mainly demonstrates low signal on T1 weighted imaging and high signal on T2 weighted imaging.It is usually enhanced significantly after iodinated contrast administration.The metastatic tumor with poor blood supply is similar to pituitary macroadenoma on magnetic resonance image,which makes it difficult to be differentiated.We reported two cases of pathologically diagnosed pituitary metastasis with poor blood supply and reviewed related papers,aiming to provide the imaging differentiation points of hypovascular pituitary metastasis.

Voxel-based quantitative susceptibility mapping revealed increased cerebral iron over the whole brain in chronic migraine.

BACKGROUND: The previous documents demonstrated that iron deposition was identified in brain deep nuclei and periaqueductal gray matter region in chronic migraine (CM), and less is known about the cerebral iron deposition in CM. The aim of this study is to investigate the cerebral iron deposition in CM using an advanced voxel-based quantitative susceptibility mapping. METHODS: A multi-echo gradient echo MR sequence was obtained from 14 CM patients and 28 normal controls (NC), and quantitative susceptibility mapping images were reconstructed and voxel-based analysis was performed over the whole cerebrum. The susceptibility value of all the positive brain regions was extracted and correlation was calculated between the susceptibility value and the clinical variables. RESULTS: The brain regions with increased susceptibility value in CM patients located in right precuneus, insula, supramarginal gyrus, dorsolateral superior frontal gyrus, postcentral gyrus, cuneus and left postcentral gyrus compared with NC. The correlation analysis demonstrated that a positive correlation was identified between susceptibility value of all the positive brain regions and VAS score. CONCLUSION: The current study demonstrated increased cerebral iron deposition presented in chronic patients, which suggested that increased cerebral iron deposition might play a role in the migraine chronicization.

Roles and Clinical Significances of ATF6, EMC6, and APAF1 in Prognosis of Pancreatic Cancer.

Background: Pancreatic cancer (PC) is prevalent among malignant tumors with poor prognosis and lacks efficient therapeutic strategies. Endoplasmic reticulum (ER) stress and apoptosis are associated with chronic inflammation and cancer progression. However, the prognostic value of ER stress-related, and apoptosis-related genes in PC remains to be further elucidated. Our study aimed at confirming the prognostic values of the ER stress-related genes, ATF6, EMC6, XBP1, and CHOP, and the apoptosis-related gene, APAF1, in PC patients. Methods: Gene Expression Profiling Interactive Analysis 2 (GEPIA2) was used to evaluate prognosis value of ATF6, EMC6, XBP1, CHOP, and APAF1 in PC. Clinical data from 69 PC patients were retrospectively analyzed. Immunohistochemistry, Western blotting, and qRT-PCR were used for the assessment of gene or protein expression. The cell counting kit-8 (CCK-8) and the Transwell invasion assays were, respectively, used for the assessment of the proliferative and invasive abilities of PC cells. The prognostic values of ATF6, XBP1, CHOP, EMC6, and APAF1 in PC patients were evaluated using Kaplan-Meier and Cox regression analyses. Results: XBP1 and CHOP expressions were not associated with PC recurrence-free survival (RFS), overall survival (OS) and disease-specific survival (DSS). ATF6 upregulation and EMC6 and APAF1 downregulations significantly correlated with the poor RFS, OS, and DSS of PC patients. ATF6 promoted PC cell proliferation and invasion, while EMC6 and APAF1 inhibited these events. Conclusion: ATF6 upregulation and EMC6 and APAF1 downregulations may be valid indicators of poor prognosis of PC patients. Moreover, ATF6, EMC6, and APAF1 may constitute potential therapeutic targets in PC patients.

[Supratentorial Primary Central Nervous System Lymphoma with Hyperperfusion:Report of One Case].

We reported a case of supratentorial primary central nervous system lymphoma with hyperperfusion.Computed tomography revealed hyperdense lesions on the bilateral centrum semiovale with obvious edema.Magnetic resonance imaging demonstrated that the lesion presented slightly long and iso-T1 signal and slightly long and long T2 signals;hyperintensity was found on diffusion-weighted imaging,with relatively high apparent diffusion coefficient value compared with the adjacent normal white matter.Contrast-enhanced imaging revealed bilateral evenly enhanced lesions,along with patchy non-enhanced shadows in right-sided lesion.The perfusion-weighted imaging revealed hyperperfusion in bilateral lesions.

[Fibrous Meningioma with Ring Enhancement in Cerebellopontine Angle Region:Report of One Case].

Fibrous meningioma is a common subtype of meningioma. Contrast-enhanced scan typically shows evident homogeneous enhancement,while ring enhancement has not been described. In this article,we report a case of fibrous meningioma with ring enhancement in cerebellopontine angle region.

Stress Myocardial Blood Flow Ratio by Dynamic CT Perfusion Identifies Hemodynamically Significant CAD.

OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of stress myocardial blood flow ratio (SFR), a novel parameter derived from stress dynamic computed tomographic perfusion (CTP), for the detection of hemodynamically significant coronary stenosis. BACKGROUND: A comprehensive cardiac computed tomographic protocol combining coronary computed tomographic angiography (CTA) and CTP can provide a simultaneous assessment of both coronary artery anatomy and ischemia. METHODS: Patients with chest pain scheduled for invasive angiography were prospectively enrolled in this study. Stress dynamic CTP was performed followed by coronary CTA using a second-generation dual-source computed tomographic system. At subsequent invasive angiography, fractional flow reserve was performed to identify hemodynamically significant stenosis. For each coronary territory, SFR was defined as the ratio of hyperemic myocardial blood flow (MBF) in an artery with stenosis to hyperemic MBF in a nondiseased artery. The diagnostic accuracy of SFR to identify hemodynamically significant stenosis was determined against the reference standard of invasive fractional flow reserve ≤0.80. RESULTS: A total of 82 patients (mean age 58.5 ± 10 years) with 101 vessels with either 1- or 2-vessel disease were included. By FFR, 48 (47.5%) vessels were deemed hemodynamically significant. Hyperemic MBF and SFR were lower for vessels with hemodynamically significant lesions (95.1 ± 32.4 ml/100 ml/min vs. 142.5 ± 31.2 ml/100 ml/min and 0.66 ± 0.14 vs. 0.90 ± 0.07, respectively; p < 0.01 for both). When compared with ≥50% stenosis by CTA, the specificity for detecting ischemia by SFR increased from 43% to 91%, while the sensitivity decreased from 95% to 62%. Accordingly, the positive and negative predictive values were 85% and 73%, respectively. The combination of stenosis ≥50% by CTA and SFR resulted in an area under the curve of 0.91, which was significantly higher compared with hyperemic MBF (area under the curve = 0.79; p = 0.013). CONCLUSIONS: Calculation of SFR by dynamic CTP provides a novel and accurate method to identify flow-limiting coronary stenosis.

Value of Texture Analysis of Intravoxel Incoherent Motion Parameters in Differential Diagnosis of Pancreatic Neuroendocrine Tumor and Pancreatic Adenocarcinoma.

Objective To evaluate the value of texture features derived from intravoxel incoherent motion (IVIM) parameters for differentiating pancreatic neuroendocrine tumor (pNET) from pancreatic adenocarcinoma (PAC).Methods Eighteen patients with pNET and 32 patients with PAC were retrospectively enrolled in this study. All patients underwent diffusion-weighted imaging with 10 b values used (from 0 to 800 s/mm 2). Based on IVIM model, perfusion-related parameters including perfusion fraction (f), fast component of diffusion (Dfast) and true diffusion parameter slow component of diffusion (Dslow) were calculated on a voxel-by-voxel basis and reorganized into gray-encoded parametric maps. The mean value of each IVIM parameter and texture features [Angular Second Moment (ASM), Inverse Difference Moment (IDM), Correlation, Contrast and Entropy] values of IVIM parameters were measured. Independent sample t-test or Mann-Whitney U test were performed for the between-group comparison of quantitative data. Regression model was established by using binary logistic regression analysis, and receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic efficiency.Results The mean f value of the pNET group were significantly higher than that of the PAC group (27.0% vs. 19.0%, P = 0.001), while the mean values of Dfast and Dslow showed no significant differences between the two groups. All texture features (ASM, IDM, Correlation, Contrast and Entropy) of each IVIM parameter showed significant differences between the pNET and PAC groups (P=0.000-0.043). Binary logistic regression analysis showed that texture ASM of Dfast and texture Correlation of Dslow were considered as the specific imaging variables for the differential diagnosis of pNET and PAC. ROC analysis revealed that multiple texture features presented better diagnostic performance than IVIM parameters (AUC 0.849-0.899 vs. 0.526-0.776), and texture ASM of Dfast combined with Correlation of Dslow in the model of logistic regression had largest area under ROC curve for distinguishing pNET from PAC (AUC 0.934, cutoff 0.378, sensitivity 0.889, specificity 0.854).Conclusions Texture analysis of IVIM parameters could be an effective and noninvasive tool to differentiate pNET from PAC.

Differential Diagnostic Value of Texture Feature Analysis of Magnetic Resonance T2 Weighted Imaging between Glioblastoma and Primary Central Neural System Lymphoma.

Objective To investigate the difference in tumor conventional imaging findings and texture features on T2 weighted images between glioblastoma and primary central neural system (CNS) lymphoma.Methods The pre-operative MRI data of 81 patients with glioblastoma and 28 patients with primary CNS lymphoma admitted to the Chinese PLA General Hospital and Hainan Hospital of Chinese PLA General Hospital were retrospectively collected. All patients underwent plain MR imaging and enhanced T1 weighted imaging to visualize imaging features of lesions. Texture analysis of T2 weighted imaging (T2WI) was performed by use of GLCM texture plugin of ImageJ software, and the texture parameters including Angular Second Moment (ASM), Contrast, Correlation, Inverse Difference Moment (IDM), and Entropy were measured. Independent sample t-test and Mann-Whitney U test were performed for the between-group comparisons, regression model was established by Binary Logistic regression analysis, and receiver operating characteristic (ROC) curve was plotted to compare the diagnostic efficacy.Results The conventional imaging features including cystic and necrosis changes (P=0.000), 'Rosette' changes (P=0.000) and 'incision sign' (P=0.000), except 'flame-like edema' (P=0.635), presented significantly statistical difference between glioblastoma and primary CNS lymphoma. The texture features, ASM, Contrast, Correlation, IDM and Entropy, showed significant differences between glioblastoma and primary CNS lympoma (P=0.006, 0.000, 0.002, 0.000, and 0.015 respectively). The area under the ROC curve was 0.671, 0.752, 0.695, 0.720 and 0.646 respectively, and the area under the ROC curve was 0.917 for the combined texture variables (Contrast, cystic and necrosis, 'Rosette' changes, and 'incision sign') in the model of Logistic regression. Binary Logistic regression analysis demonstrated that cystic and necrosis changes, 'Rosette' changes and 'incision sign' and texture Contrast could be considered as the specific texture variables for the differential diagnosis of glioblastoma and primary CNS lymphoma.Conclusions The texture features of T2WI and conventional imaging findings may be used to distinguish glioblastoma from primary CNS lymphoma.

Value of Magnetic Resonance Imaging Texture Analysis in the Differential Diagnosis of Benign and Malignant Breast Tumors.

Objective To investigate the difference in texture features on diffusion weighted imaging (DWI) images between breast benign and malignant tumors.Methods Patients including 56 with mass-like breast cancer, 16 with breast fibroadenoma, and 4 with intraductal papilloma of breast treated in the Hainan Hospital of Chinese PLA General Hospital were retrospectively enrolled in this study, and allocated to the benign group (20 patients) and the malignant group (56 patients) according to the post-surgically pathological results. Texture analysis was performed on axial DWI images, and five characteristic parameters including Angular Second Moment (ASM), Contrast, Correlation, Inverse Difference Moment (IDM), and Entropy were calculated. Independent sample t-test and Mann-Whitney U test were performed for intergroup comparison. Regression model was established by using Binary Logistic regression analysis, and receiver operating characteristic curve (ROC) analysis was carried out to evaluate the diagnostic efficiency.Results The texture features ASM, Contrast, Correlation and Entropy showed significant differences between the benign and malignant breast tumor groups (PASM=0.014, Pcontrast=0.019, Pcorrelation=0.010, Pentropy=0.007). The area under the ROC curve was 0.685, 0.681, 0.754, and 0.683 respectively for the positive texture variables mentioned above, and that for the combined variables (ASM, Contrast, and Entropy) was 0.802 in the model of Logistic regression. Binary Logistic regression analysis demonstrated that ASM, Contrast and Entropy were considered as the specific imaging variables for the differential diagnosis of breast benign and malignant tumors.Conclusions The texture analysis of DWI may be a simple and effective tool in the differential diagnosis between breast benign and malignant tumors.

Altered functional connectivity of the marginal division in Parkinson's disease with mild cognitive impairment: A pilot resting-state fMRI study.

BACKGROUND: The marginal division (MrD) is an important subcortical center involved in learning and memory. Mild cognitive impairment (MCI) is commonly seen in patients with Parkinson's disease (PD), but the neurobiological basis is yet to be elucidated. PURPOSE: To use resting-state functional magnetic resonance imaging (rs-fMRI) to explore the altered functional connectivity (FC) of the MrD in patients with PD-MCI. STUDY TYPE: Prospective pilot study. POPULATION: Twenty-five patients with PD-MCI; 25 PD patients and no cognitive impairment (PD-NCI); and 25 healthy control (HC) participants. SEQUENCE: 3.0 T GE Healthcare MRI scanner; three-dimensional T1 -weighted fast spoiled gradient recalled echo (3D T1 -FSPGR); rs-fMRI. ASSESSMENT: The MrD was defined using manual delineation, which was the seed point to compute the FC to examine correlations between low-frequency fMRI signal fluctuations in MrD and the whole brain. STATISTICAL TESTS: Between-group comparisons of the rs-fMRI data were computed using two-sample t-tests in a voxelwise manner after controlling for age and sex, to determine the brain regions that showed significant differences in FC with the bilateral MrDs. Correlation analyses were performed for FC values and cognitive abilities in patients with PD. RESULTS: In the PD-MCI group, compared with the PD-NCI group, we observed lesser FC between the MrD bilaterally and right putamen, left insula, left cerebellum, and left thalamus; greater FC between the MrD bilaterally and left middle cingulate cortex, left middle frontal gyrus, left superior frontal gyrus, left supplementary motor area, and left middle/inferior occipital gyrus. Moreover, the strength of FC between the MrD and regions that showed differences between the PD-MCI and PD-NCI groups was significantly correlated with neuropsychological scores in patients with PD. DATA CONCLUSION: The current study suggests that MrD dysfunction may contribute to MCI in PD. However, the mechanisms underlying this process require further investigation. Level of Evidence 1. Technical Efficacy Stage 2. J. Magn. Reson. Imaging 2019;50:183-192.

[Multicystic Encephalomalacia:Report of One Case].

The magnetic resonance imaging findings of multicystic encephalomalacia are featured by bilateral frontal large cystic lesion with corpus callosum involvement,evident heterogeneous enhancement of the lesion margin,ring hyperintensity on diffusion weighted imaging,and high choline peak and low N-acetylaspartate peak of the enhanced lesion margin on magnetic resonance spectroscopy.This article reports a case of multicystic encephalomalacia.