Prognostic value of right ventricular trabecular complexity in patients with arrhythmogenic cardiomyopathy.

OBJECTIVES: The present study aimed to investigate the incremental prognostic value of the right ventricular fractal dimension (FD), a novel marker of myocardial trabecular complexity by cardiac magnetic resonance (CMR) in patients with arrhythmogenic cardiomyopathy (ACM). METHODS: Consecutive patients with ACM undergoing CMR were followed up for major cardiac events, including sudden cardiac death, aborted cardiac arrest, and appropriate implantable cardioverter defibrillator intervention. Prognosis prediction was compared by Cox regression analysis. We established a multivariable model supplemented with RV FD and evaluated its discrimination by Harrell's C-statistic. We compared the category-free, continuous net reclassification improvement (cNRI) and integrated discrimination index (IDI) before and after the addition of FD. RESULTS: A total of 105 patients were prospectively included from three centers and followed up for a median of 60 (48, 66) months; experienced 36 major cardiac events were recorded. Trabecular FD displayed a strong unadjusted association with major cardiac events (p < 0.05). In the multivariable Cox regression analysis, RV maximal apical FD maintained an independent association with major cardiac events (hazard ratio, 1.31 (1.11-1.55), p < 0.002). The Hosmer-Lemeshow goodness of fit test displayed good fit (X2 = 0.68, p = 0.99). Diagnostic performance was significantly improved after the addition of RV maximal apical FD to the multivariable baseline model, and the continuous net reclassification improvement increased 21% (p = 0.001), and the integrated discrimination index improved 16% (p = 0.045). CONCLUSIONS: In patients with ACM, CMR-assessed myocardial trabecular complexity was independently correlated with adverse cardiovascular events and provided incremental prognostic value. CLINICAL RELEVANCE STATEMENT: The application of FD values for assessing RV myocardial trabeculae may become an accessible and promising parameter in monitoring and early diagnosis of risk factors for adverse cardiovascular events in patients with ACM. KEY POINTS: • Ventricular trabecular morphology, a novel quantitative marker by CMR, has been explored for the first time to determine the severity of ACM. • Patients with higher maximal apical fractal dimension of RV displayed significantly higher cumulative incidence of major cardiac events. • RV maximal apical FD was independently associated with major cardiac events and provided incremental prognostic value in patients with ACM.

Pediatric Hepatoblastoma After Neoadjuvant Chemotherapy: Diagnostic Performance of MR in Staging POSTTEXT and Vascular Involvement.

BACKGROUND: The assessment of resectability after neoadjuvant chemotherapy of hepatoblastoma is dependent on Post-Treatment EXTENT of Disease (POSTTEXT) staging and its annotation factors P (portal venous involvement) and V (hepatic venous/inferior vena cava [IVC] involvement), but MR performance in assessing them remains unclear. PURPOSE: To assess the diagnostic performance of contrast-enhanced MR imaging for preoperative POSTTEXT staging and diagnosing vascular involvement in terms of annotation factors P and V in pediatric hepatoblastoma following neoadjuvant chemotherapy. STUDY TYPE: Retrospective. SUBJECTS: Thirty-five consecutive patients (17 males, median age, 24 months; age range, 6-98 months) with proven hepatoblastoma underwent preoperative MR imaging following neoadjuvant chemotherapy. FIELD STRENGTH/SEQUENCE: 3.0 T; T2-weighted imaging (T2WI), T2WI with fat suppression, diffusion weighted imaging, radial stack-of-the-star/Cartesian 3D Dixon T1-weighted gradient echo imaging. ASSESSMENT: Three radiologists independently assessed the POSTTEXT stages and annotation factors P and V based on the 2017 PRE/POSTTEXT system. The sensitivities and specificities were calculated for 1) diagnosing each POSTTEXT stage; 2) discrimination of stages III and IV (advanced) from those stages I and II (non-advanced) hepatoblastomas; and 3) annotation factors P and V. The combination of pathologic findings and surgical records served as the reference standard. STATISTICAL TESTS: Sensitivity, specificity, Fleiss kappa test. RESULTS: The sensitivity and specificity ranges for discriminating advanced from non-advanced hepatoblastomas were 73.3%-80.0% and 80.0%-90.0%, respectively. For annotation factor P, they were 66.7%-100.0% and 90.6%, respectively. For factor V, they were 75.0% and 67.7%-83.9%, respectively. There was excellent, substantial, and moderate agreement on POSTTEXT staging (Fleiss kappa = 0.82), factors P (Fleiss kappa = 0.64), and factors V (Fleiss kappa = 0.60), respectively. DATA CONCLUSION: MR POSTTEXT provides reliable discrimination between advanced and non-advanced tumors, and MR has moderate to excellent specificity at identifying portal venous and hepatic venous/IVC involvement. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Discovery of the covalent SARS-CoV-2 Mpro inhibitors from antiviral herbs via integrating target-based high-throughput screening and chemoproteomic approaches.

The main proteases (Mpro ) are highly conserved cysteine-rich proteins that can be covalently modified by numerous natural and synthetic compounds. Herein, we constructed an integrative approach to efficiently discover covalent inhibitors of Mpro from complex herbal matrices. This work begins with biological screening of 60 clinically used antiviral herbal medicines, among which Lonicera japonica Flos (LJF) demonstrated the strongest anti-Mpro effect (IC50 = 37.82 µg/mL). Mass spectrometry (MS)-based chemical analysis and chemoproteomic profiling revealed that LJF extract contains at least 50 constituents, of which 22 exhibited the capability to covalently modify Mpro . We subsequently verified the anti-Mpro effects of these covalent binders. Gallic acid and quercetin were found to potently inhibit severe acute respiratory syndrome coronavirus 2 Mpro in dose- and time- dependent manners, with the IC50 values below 10 µM. The inactivation kinetics, binding affinity and binding mode of gallic acid and quercetin were further characterized by fluorescence resonance energy transfer, surface plasmon resonance, and covalent docking simulations. Overall, this study established a practical approach for efficiently discovering the covalent inhibitors of Mpro from herbal medicines by integrating target-based high-throughput screening and MS-based assays, which would greatly facilitate the discovery of key antiviral constituents from medicinal plants.

Prognostic significance of non-infarcted myocardium correlated with microvascular impairment evaluated dynamically by native T1 mapping.

OBJECTIVES: This study aimed to investigate the influence of microvascular impairment on myocardial characteristic alterations in remote myocardium at multiple time points, and its prognostic significance after acute ST-segment elevation myocardial infarction (STEMI). METHODS: Patients were enrolled prospectively and performed CMR at baseline, 30 days, and 6 months. The primary endpoint was major adverse cardiac events (MACE): death, myocardial reinfarction, malignant arrhythmia, and hospitalization for heart failure. Cox proportional hazards regression modeling was analyzed to estimate the correlation between T1 mapping of remote myocardium and MACE in patients with and without microvascular obstruction (MVO). RESULTS: A total of 135 patients (mean age 60.72 years; 12.70% female, median follow-up 510 days) were included, of whom 86 (63.70%) had MVO and 26 (19.26%) with MACE occurred in patients. Native T1 values of remote myocardium changed dynamically. At 1 week and 30 days, T1 values of remote myocardium in the group with MVO were higher than those without MVO (p = 0.030 and p = 0.001, respectively). In multivariable cox regression analysis of 135 patients, native1w T1 (HR 1.03, 95%CI 1.01-1.04, p = 0.002), native30D T1 (HR 1.05, 95%CI 1.03-1.07, p < 0.001) and LGE (HR 1.10, 95%CI 1.05-1.15, p < 0.001) were joint independent predictors of MACE. In multivariable cox regression analysis of 86 patients with MVO, native30D T1 (HR 1.05, 95%CI 1.04-1.07, p < 0.001) and LGE (HR 1.10, 95%CI 1.05-1.15, p < 0.001) were joint independent predictors of MACE. CONCLUSIONS: The evolution of native T1 in remote myocardium was associated with the extent of microvascular impairment after reperfusion injury. In patients with MVO, native30D T1 and LGE were joint independent predictors of MACE.

Atypical and uncommon CT and MR imaging presentations of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinomas (PDACs) occasionally have atypical and uncommon imaging presentations that can present a diagnostic dilemma and result in false interpretation. This article aimed to illustrate these CT and MR imaging findings, including isoattenuating PDAC, coexisting acute pancreatitis, PDAC with a cystic feature, groove PDAC, diffuse PDAC, hypointensity on diffusion-weighted imaging (DWI), multifocal PDAC, intratumoral calcification, and extrapancreatic invasion with a barely discernable mass. A subset of PDACs with atypical features are occasionally encountered during routine clinical practice. Knowledge of and attention to these atypical and uncommon variable imaging features may allow radiologists to avoid misinterpretation and a delayed diagnosis.

Comparison of malignancy-prediction efficiency between contrast and non-contract CT-based radiomics features in gastrointestinal stromal tumors: A multicenter study.

This work seeks the development and validation of radiomics signatures from nonenhanced computed tomography (CT, NE-RS) to preoperatively predict the malignancy degree of gastrointestinal stromal tumors (GISTs) and the comparison of these signatures with those from contrast-enhanced CT. A dataset for 370 GIST patients was collected from four centers. This dataset was divided into cohorts for training, as well as internal and external validation. The minimum-redundancy maximum-relevance algorithm and the least absolute shrinkage and selection operator (LASSO) algorithm were used to filter unstable features. (a) NE-RS and radiomics signature from contrast-enhanced CT (CE-RS) were built and compared for the prediction of malignancy potential of GIST based on the area under the receiver operating characteristic curve (AUC). (b) The radiomics model was also developed with both the tumor size and NE-RS. The AUC values were comparable between NE-RS and CE-RS in the training (.965 vs .936; P = .251), internal validation (.967 vs .960; P = .801), and external validation (.941 vs .899; P = .173) cohorts in diagnosis of high malignancy potential of GISTs. We next focused on the NE-RS. With 0.185 selected as the cutoff of NE-RS for diagnosis of the malignancy potential of GISTs, accuracy, sensitivity, and specificity for diagnosis high-malignancy potential GIST was 90.0%, 88.2%, and 92.3%, respectively, in the training cohort. For the internal validation set, the corresponding metrics are 89.1%, 94.9%, and 80.0%, respectively. The corresponding metrics for the external cohort are 84.6%, 76.1%, and 91.0%, respectively. Compared with only NE-RS, the radiomics model increased the sensitivity in the diagnosis of GIST with high-malignancy potential by 5.9% (P = .025), 2.5% (P = .317), 10.5% (P = .008) for the training set, internal validation set, and external validation set, respectively. The NE-RS had comparable prediction efficiency in the diagnosis of high-risk GISTs to CE-RS. The NE-RS and radiomics model both had excellent accuracy in predicting malignancy potential of GISTs.

Determining the invasiveness of pure ground-glass nodules using dual-energy spectral computed tomography.

BACKGROUND: The present work aimed to investigate the clinical application of using quantitative parameters generated in the unenhanced phase (UP) and venous phase (VP) in dual-energy spectral CT for differentiating the invasiveness of pure ground-glass nodule (pGGN). METHODS: Sixty-two patients with 66 pGGNs who underwent preoperative dual-energy spectral CT in UP and VP were evaluated retrospectively. Nodules were divided into three groups based on pathology: adenocarcinoma in situ (AIS, n=19), minimally invasive adenocarcinoma (MIA, n=22) (both in the preinvasive lesion group) and invasive adenocarcinoma (IA, n=25). The iodine concentration (IC) and water content (WC) in nodules were measured in material decomposition images. The nodule CT numbers and slopes(k) were measured on monochromatic images. All measurements, including the maximum diameter of nodules were statistically compared between the AIS-MIA group and IA group. RESULTS: There were significant differences of WC in VP between AIS-MIA group and IA group (P<0.05). The CT attenuation values of the 40-140 keV monochromatic images in UP and VP were significantly higher for the invasive nodules. Logistic regression analysis showed that the maximum nodule diameter [odd ratio (OR) =1.21, 95% CI: 1.050-1.400, P<0.01] and CT number in 130 keV images in venous phase (OR =1.03, 95% CI: 1.014-1.047, P<0.001) independently predicted histological invasiveness. CONCLUSIONS: The quantitative parameters in dual-energy spectral CT in the unenhanced phase and venous phase provide useful information in differentiating preinvasive lesion group from IA group of pGGN, especially the maximum nodule diameter and CT number in the 130 keV images in the venous phase.

Personalized CT-based radiomics nomogram preoperative predicting Ki-67 expression in gastrointestinal stromal tumors: a multicenter development and validation cohort.

BACKGROUND AND AIM: To develop and validate radiomic prediction models using contrast-enhanced computed tomography (CE-CT) to preoperatively predict Ki-67 expression in gastrointestinal stromal tumors (GISTs). METHOD: A total of 339 GIST patients from four centers were categorized into the training, internal validation, and external validation cohort. By filtering unstable features, minimum redundancy, maximum relevance, Least Absolute Shrinkage and Selection Operator (LASSO) algorithm, a radiomic signature was built to predict the malignant potential of GISTs. Individual nomograms of Ki-67 expression incorporating the radiomic signature or clinical factors were developed using the multivariate logistic model and evaluated regarding its calibration, discrimination, and clinical usefulness. RESULTS: The radiomic signature, consisting of 6 radiomic features had AUC of 0.787 [95% confidence interval (CI) 0.632-0.801], 0.765 (95% CI 0.683-0.847), and 0.754 (95% CI 0.666-0.842) in the prediction of high Ki-67 expression in the training, internal validation and external validation cohort, respectively. The radiomic nomogram including the radiomic signature and tumor size demonstrated significant calibration, and discrimination with AUC of 0.801 (95% CI 0.726-0.876), 0.828 (95% CI 0.681-0.974), and 0.784 (95% CI 0.701-0.868) in the training, internal validation and external validation cohort respectively. Based on the Decision curve analysis, the radiomics nomogram was found to be clinically significant and useful. CONCLUSIONS: The radiomic signature from CE-CT was significantly associated with Ki-67 expression in GISTs. A nomogram consisted of radiomic signature, and tumor size had maximum accuracy in the prediction of Ki-67 expression in GISTs. Results from our study provide vital insight to make important preoperative clinical decisions.

Carbocisteine Improves Histone Deacetylase 2 Deacetylation Activity via Regulating Sumoylation of Histone Deacetylase 2 in Human Tracheobronchial Epithelial Cells.

Histone deacetylase (HDAC) 2 plays a vital role in modifying histones to mediate inflammatory responses, while HDAC2 itself is commonly regulated by post-translational modifications. Small ubiquitin-related modifier (SUMO), as an important PTM factor, is involved in the regulation of multiple protein functions. Our previous studies have shown that carbocisteine (S-CMC) reversed cigarette smoke extract (CSE)-induced down-regulation of HDAC2 expression/activity in a thiol/GSH-dependent manner and enhanced sensitivity of steroid therapy. However, the mechanism by which S-CMC regulates HDAC2 is worth further exploring. Our study aimed to investigate the relationships between HDAC2 sumoylation and its deacetylase activity under oxidative stress and the molecular mechanism of S-CMC to regulate HDAC2 activity that mediates inflammatory responses in human bronchial epithelial cells. We found that modification of HDAC2 by SUMO1 and SUMO2/3 occurred in 16HBE cells under physiological conditions, and CSE induced SUMO1 modification of HDAC2 in a dose and time-dependent manner. K462 and K51 of HDAC2 were the two major modification sites of SUMO1, and the K51 site mediated deacetylation activity and function of HDAC2 on histone H4 that regulates IL-8 secretion. S-CMC inhibited CSE-induced SUMO1 modification of HDAC2 in the presence of thiol/GSH, increased HDAC activity, and decreased IL-8 expression. Our study may provide novel mechanistic explanation of S-CMC to ameliorate steroid sensitivity treatment in chronic obstructive pulmonary disease.

M1 muscarinic receptors regulate the phosphorylation of AMPA receptor subunit GluA1 via a signaling pathway linking cAMP-PKA and PI3K-Akt.

M1 muscarinic acetylcholine receptors are highly expressed in key areas that control cognition, such as the cortex and hippocampus, representing one potential therapeutic target for cognitive dysfunctions of Alzheimer's disease and schizophrenia. We have reported that M1 receptors facilitate cognition by promoting membrane insertion of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor AMPA receptor subunit 1 (GluA1) through phosphorylation at Ser845. However, the signaling pathway is still unclear. Here we showed that adenylyl cyclase inhibitor 2',5'-dideoxyadenosine and PKA inhibitor KT5720 inhibited enhancement of phosphorylation of Ser845 and membrane insertion of GluA1 induced by M1 receptor activation. Furthermore, PI3K inhibitor LY294002 and protein kinase B (Akt) inhibitor IV blocked the effects of M1 receptors as well. Remarkably, the increase of the activity of PI3K-Akt signaling induced by M1 receptor activation could be abolished by cAMP-PKA inhibitors. Moreover, inhibiting the mammalian target of rapamycin (mTOR) complex 1, an important downstream effector of PI3K-Akt, by short-term application of rapamycin attenuated the effects of M1 receptors on GluA1. Furthermore, such effect was unrelated to possible protein synthesis promoted by mTOR. Taken together, these data demonstrate that M1 receptor activation induces membrane insertion of GluA1 via a signaling linking cAMP-PKA and PI3K-Akt-mTOR pathways but is irrelevant to protein synthesis.-Zhao, L.-X., Ge, Y.-H., Li, J.-B., Xiong, C.-H., Law, P.-Y., Xu, J.-R., Qiu, Y., Chen, H.-Z. M1 muscarinic receptors regulate the phosphorylation of AMPA receptor subunit GluA1 via a signaling pathway linking cAMP-PKA and PI3K-Akt.

Diffusion kurtosis imaging to assess correlations with clinicopathologic factors for bladder cancer: a comparison between the multi-b value method and the tensor method.

OBJECTIVES: To assess the efficacy of diffusion kurtosis imaging (DKI) in differentiating low-grade from high-grade tumors and evaluating the aggressiveness of bladder cancer. METHODS: From January 2017 to July 2017, 35 patients (28 males, 7 females; mean age 63 ± 9 years) diagnosed with bladder cancer underwent diffusion-weighted imaging (DWI) with two types of DKI protocols: (1) multi-b value ranging from 0 to 2000 s/mm2 to obtain mean diffusivity/kurtosis (MDb/MKb) and (2) the tensor method with 32 directions with 3 b values (0, 1000, and 2000s/mm2) to obtain mean/axial/radial diffusivity (MDt/Da/Dr), mean/axial/radial kurtosis (MKt/Ka/Kr), and fractional anisotropy (FA) before radical cystectomy. Comparisons between the low- and high-grade groups, non-muscle-invasive bladder cancer (NMIBC), and muscle-invasive bladder cancer (MIBC) were performed with the areas under the receiver operating characteristic curves (AUCs). RESULTS: The MKt and Kr values were significantly (p = 0.017 and p = 0.048) higher in patients with high-grade bladder tumors than in those with low-grade tumors. The MKt, Kr, and MKb values were significantly (p = 0.022, p = 0.000, and p = 0.044, respectively) higher in patients with MIBC than in those with NMIBC, while no significant differences (p > 0.05) were found in other values. The AUC of Kr (0.883) was the largest and was significantly higher than those of other metrics (all p < 0.05) for differentiating MIBC from NMIBC, with a sensitivity and specificity of 81.8% and 91.7%, respectively. CONCLUSIONS: Kurtosis metrics performed better than diffusion metrics in differentiating MIBC from NMIBC, and directional kurtosis and Kr metrics may also have great potential in providing additional information regarding bladder cancer invasiveness. KEY POINTS: • Kurtosis metrics performed better than diffusion metrics in differentiating muscle-invasive bladder cancer (MIBC) from non-muscle-invasive bladder cancer (NMIBC). • Directional kurtosis can provide additional directional microstructural information regarding bladder cancer invasiveness.

Dual Energy Spectral CT Imaging in the assessment of Gastric Cancer and cell proliferation: A Preliminary Study.

Gastric cancer is one of the main diseases leading to cancer-related death. The recently introduced dual-energy spectral CT (DEsCT), allows to obtain many quantitative measurements from iodine-based material decomposition (MD) images, which contribute to improve the accuracy of staging of GC comparing to multidetector spiral CT. And Ki-67 is a well-recognized nuclear antigen-specific biomarker reflecting cellular proliferation for estimating growth fractions of various tumor types. In the present study we analyzed the features of quantitative measurements (the curve slope (λHU), IC, normalized iodine concentrations (NIC)) obtained from DEsCT and levels of Ki-67 protein expression. We demonstrated that the values between advanced gastric cancer (AGC) and early gastric cancer (EGC) were significantly different both in venous phase (VP) and delayed phase (DP). The values of different level of Ki-67 expression grade were significantly different both in VP and DP. The rank correlation analysis between Ki-67 grade and IC, NIC and λHU values showed significantly positive correlation in VP and DP. These results suggested that quantitative parameters (IC, NIC and λHU) in dual-energy CT imaging can be used to differentiate EGC from AGC, and have significantly positive correlation with Ki-67 antigen expression levels in gastric cancer for indicating tumor cellular proliferation.

Intravoxel incoherent motion diffusion-weighted imaging in assessing bladder cancer invasiveness and cell proliferation.

BACKGROUND: Nonmuscle-invasive bladder cancer (NMIBC, Stage T1 or lower) is treated with transurethral resection (TUR), while muscle-invasive bladder cancer (MIBC, Stage T2 or more) requires neoadjuvant chemotherapy before radical cystectomy. Hence, preoperative differentiation is vital. PURPOSE: To investigate whether intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) can differentiate NMIBC from MIBC and to assess whether there were correlations between IVIM parameters and the Ki-67 labeling index (LI). STUDY TYPE: Retrospective. SUBJECTS: Thirty-six patients diagnosed with bladder cancer confirmed by histopathological findings. FIELD STRENGTH/SEQUENCE: 3.0T magnetic resonance imaging (MRI) DWI with eight b-values ranging from 0 to 1000 s/mm2 . ASSESSMENT: Molecular diffusion coefficient (D), perfusion-related diffusion coefficient (D*), perfusion fraction (f), and apparent diffusion coefficient (ADC) were calculated by biexponential and monoexponential models fits, respectively. STATISTICAL TESTS: Comparisons were made between the MIBC and NMIBC group, and differences were analyzed by comparing the areas under the receiver-operating characteristic curves (AUCs). The correlations between these parameters and Ki-67 LI were assessed by Spearman's rank correlation analysis. RESULTS: The ADC and D value were significantly lower in patients with MIBC compared to those with NMIBC (P < 0.01). No significant (P > 0.05) differences were observed in D* and f. The AUC of D value (0.894) was significantly (P < 0.05) larger than the ADC value (0.786), with sensitivities and specificities of 95% and 87.5% (D) and 80% and 68.7% (ADC), respectively. In addition, the D and ADC values were significantly correlated with Ki-67 LI (r = -0.785, r = -0.643, respectively; both P < 0.01). DATA CONCLUSION: The D value obtained from IVIM exhibited better performance than conventional DWI for distinguishing NMIBC from MIBC and may serve as a potential imaging biomarker for bladder cancer invasion. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1054-1060.

Breast Lesions: Diagnosis Using Diffusion Weighted Imaging at 1.5T and 3.0T-Systematic Review and Meta-analysis.

INTRODUCTION: We compared the diagnostic performance of diffusion weighted imaging (DWI) acquired with 1.5T and 3.0T magnetic resonance (MR) units in differentiating malignant breast lesions from benign ones. MATERIALS AND METHODS: A comprehensive search of the PubMed and Embase databases was performed for studies reported from January 1, 2000 to February 19, 2016. The quality of the included studies was assessed. Statistical analysis included pooling of diagnostic sensitivity and specificity and assessing data inhomogeneity and publication bias. RESULTS: A total of 61 studies were included after a full-text review. These included 4778 patients and 5205 breast lesions. The overall sensitivity and specificity were 90% (95% confidence interval [CI], 88%-92%) and 86% (95% CI, 82%-89%), respectively. The pooled diagnostic odds ratio was 53 (95% CI, 37-74). For breast cancer versus benign lesions, the area under the curve was 0.94 (95% CI, 0.92-0.96). For the 44 studies that used a 1.5T MR unit, the pooled sensitivity and specificity were 91% (95% CI, 89%-92%) and 86% (95% CI, 81%-90%), respectively. For the 17 studies that used a 3.0T MR unit, the pooled sensitivity and specificity were 88% (95% CI, 83%-91%) and 84% (95% CI, 0.78-0.89), respectively. Publication bias and significant heterogeneity were observed; however, no threshold was found among the 61 studies. No significant difference was found in the sensitivity or specificity between the subgroups. CONCLUSION: The results of the comparison between the subgroups that had used either a 1.5T or 3.0T MR unit suggest that the diagnostic accuracy for breast cancer compared with benign lesions is not significantly different.

Regulation and effects of neurotrophic factors after neural stem cell transplantation in a transgenic mouse model of Alzheimer disease.

According to much research, neurodegeneration and cognitive decline in Alzheimer disease (AD) are correlated with alternations of neurotrophic factors such as nerve growth factor, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor. The experimental illumination of neural stem cell (NSC) transplantation to eliminate AD symptoms is being explored frequently, and we have acknowledged that neurotrophic factors may play a pivotal role in cognitive improvement. However, the relation between the reversal of cognitive deficits after NSC transplantation and directed alternations of neurotrophic factors is not clearly expounded. Meanwhile, reduced inflammatory response, promoted vessel density, and vascular endothelial growth factor (VEGF) can be reflections of improvement in cerebrovascular function. Three weeks after NSC transplantation, spatial learning and memory function in NSC-injected (Tg-NSC) mice were significantly improved compared with vehicle-injected (Tg-Veh) mice. Meanwhile, results obtained by immunofluorescence and Western blot analyses demonstrated that the levels of neurotrophic factors, VEGF, and vessel density in the cortex of Tg-NSC mice were significantly enhanced compared with Tg-Veh mice, while the levels of proinflammatory cytokines interleukin (IL)-1ß, tumor necrosis factor-α, and IL-6 were significantly decreased. Our results suggest that elevated concentrations of neurotrophic factors probably play a critical role in rescuing cognitive dysfunction in APP/PS1 transgenic mice after NSC transplantation, and neurotrophic factors may improve cerebrovascular function by means such as reducing inflammatory response and promoting angiogenesis.

NSCs promote hippocampal neurogenesis, metabolic changes and synaptogenesis in APP/PS1 transgenic mice.

Adult neurogenesis and synaptic remodeling persist as a unique form of structural and functional plasticity in the hippocampal dentate gyrus (DG) and subventricular zone (SVZ) of the lateral ventricles due to the existence of neural stem cells (NSCs). Transplantation of NSCs may represent a promising approach for the recovery of neural circuits. Here, we aimed to examine effects of highly neuronal differentiation of NSCs transplantation on hippocampal neurogenesis, metabolic changes and synaptic formation in APP/PS1 mice. 12-month-old APP/PS1 mice were used for behavioral tests, immunohistochemistry, western blot, transmission electron microscopy and proton magnetic resonance spectroscopy (1H-MRS). The results showed that N-acetylaspartate (NAA) and Glutamate (Glu) levels were increased in the Tg-NSC mice compared with the Tg-PBS and Tg-AD mice 10 weeks after NSCs transplantation. NSC-induced an increase in expression of synaptophysin and postsynaptic protein-95, and the number of neurons with normal synapses was significantly increased in Tg-NSC mice. More doublecortin-, BrdU/NeuN- and Nestin-positive neurons were observed in the hippocampal DG and SVZ of the Tg-NSC mice. This is the first demonstration that engrafted NSCs with a high differentiation rate to neurons can enhance neurogenesis in a mouse model of AD and can be detected by 1H-MRS in vivo. It is suggested that engraft of NSCs can restore memory and promote endogenous neurogenesis and synaptic remodeling, moreover, 1H-MRS can detect metabolite changes in AD mice in vivo. The observed changes in NAA/creatine (Cr) and glutamate (Glu)/Cr may be correlated with newborn neurons and new synapse formation.

Preliminary study of diffusion kurtosis imaging in thyroid nodules and its histopathologic correlation.

OBJECTIVES: To evaluate the utility of diffusion kurtosis imaging (DKI) of patients with thyroid nodules and to assess the probable correlation with histopathological factors. METHODS: The study included 58 consecutive patients with thyroid nodules who underwent magnetic resonance imaging (MRI) examination, including DKI and diffusion-weighted imaging (DWI). Histopathological analysis of paraffin sections included cell density and immunohistochemical analysis of Ki-67 and vascular endothelial growth factor (VEGF). Statistical analyses were performed using Student's t-test, receiver operating characteristic (ROC) curves and Spearman's correlation. RESULTS: The diffusion parameters, cell density and immunohistochemistry analysis between malignant and benign lesions showed significant differences. The largest area under the ROC curve was acquired for the D value (AUC = 0.797). The highest sensitivity was shown with the use of K (threshold = 0.832, sensitivity = 0.917). The Ki-67 expression generally stayed low. A moderate correlation was found between ADC, D and cell density (r = -0.536, P = 0.000; r = -0.570, P = 0.000) and ADC, D and VEGF expression (r = -0.451, P = 0.000; r = -0.522, P = 0.000). CONCLUSION: The DKI-derived parameters D and K demonstrated an advantage compared to conventional DWI for thyroid lesion diagnosis. While the histopathological study indicated that the D value correlated better with extracellular change than the ADC value, the K value probably changed relative to the intracellular structure. KEY POINTS: • DWI and DKI parameters can identify PTC from benign thyroid nodules. • Correlations were found between diffusion parameters and histopathological analysis. • DKI obtains better diagnostic accuracy than conventional DWI.