HK2 and LDHA upregulation mediate hexavalent chromium-induced carcinogenesis, cancer development and prognosis through miR-218 inhibition.

Hexavalent chromium [Cr(VI)] is one of the most common environmental contaminants due to its tremendous industrial applications, but its effects and mechanism remain to be investigated. Our previous studies showed that Cr(VI) exposure caused malignant transformation and tumorigenesis. This study showed that glycolytic proteins HK2 and LDHA levels were statistically significant changed in blood samples of Cr(VI)-exposed workers and in Cr-T cells compared to the control subjects and parental cells. HK2 and LDHA knockdown inhibited cell proliferation and angiogenesis, and higher HK2 and LDHA expression levels are associated with advanced stages and poor prognosis of lung cancer. We found that miR-218 levels were significantly decreased and miR-218 directly targeted HK2 and LDHA for inhibiting their expression. Overexpression of miR-218 inhibited glucose consumption and lactate production in Cr-T cells. Further study found that miR-218 inhibited tumor growth and angiogenesis by decreasing HK2 and LDHA expression in vivo. MiR-218 levels were negatively correlated with HK2 and LDHA expression levels and cancer development in human lung and other cancers. These results demonstrated that miR-218/HK2/LDHA pathway is vital for regulating Cr(VI)-induced carcinogenesis and human cancer development.

Multimodality MRI Radiomics Based on Machine Learning for Identifying True Tumor Recurrence and Treatment-Related Effects in Patients with Postoperative Glioma.

INTRODUCTION: Conventional magnetic resonance imaging (MRI) features have difficulty distinguishing glioma true tumor recurrence (TuR) from treatment-related effects (TrE). We aimed to develop a machine-learning model based on multimodality MRI radiomics to help improve the efficiency of identifying glioma TuR. METHODS: A total of 131 patients were enrolled and randomly divided into the training set (n = 91) and the test set (n = 40). Radiomic features were extracted from the postoperative enhancement (PoE) region and edema (ED) region from four routine MRI sequences. After analyses of Spearman's rank correlation coefficient, and least absolute shrinkage and selection operator, the key radiomic features were selected to construct support vector machine (SVM) and k-nearest neighbor (KNN) models. Decision curve analysis (DCA) and receiver operating characteristic (ROC) curves were used to analyze the performance. RESULTS: The PoE model had a significantly higher area under curve (AUC) than the ED model (p < 0.05). Among the models constructed with a single sequence, the model using PoE regional features from CE-T1WI was superior to other models, with an AUC of 0.905 for SVM and 0.899 for KNN. In multimodality models, the PoE model outperformed the ED model with an AUC of 0.931 for SVM and 0.896 for KNN. The multimodality model, which combined routine sequences and the whole regional features, showed a slightly better performance with an AUC of 0.965 for SVM and 0.955 for KNN. Decision curve analysis showed the good clinical utility of multimodal radiomics models. CONCLUSIONS: Multimodality radiomics can identify glioma TuR and TrE, potentially aiding clinical decision-making for individualized treatment. And edematous regions may provide useful information for recognizing recurrence. RETROSPECTIVELY REGISTERED: 2021.04.15, No:2020039.

Elevated NOX4 promotes tumorigenesis and acquired EGFR-TKIs resistance via enhancing IL-8/PD-L1 signaling in NSCLC.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been widely used for human non-small-cell lung cancer (NSCLC) treatment. However, acquired resistance to EGFR-TKIs is the major barrier of treatment success, and new resistance mechanism remains to be elucidated. In this study, we found that elevated NADPH oxidase 4 (NOX4) expression was associated with acquired EGFR-TKIs resistance. Gefitinib is the first-generation FDA-approved EGFR-TKI, and osimertinib is the third-generation FDA-approved EGFR-TKI. We demonstrated that NOX4 knockdown in the EGFR-TKI resistant cells enabled the cells to become sensitive to gefitinib and osimertinib treatment, while forced expression of NOX4 in the sensitive parental cells was sufficient to induce resistance to gefitinib and osimertinib in the cells. To elucidate the mechanism of NOX4 upregulation in increasing TKIs resistance, we found that knockdown of NOX4 significantly down-regulated the expression of transcription factor YY1. YY1 bound directly to the promoter region of IL-8 to transcriptionally activate IL-8 expression. Interestingly, knockdown of NOX4 and IL-8 decreased programmed death ligand 1 (PD-L1) expression, which provide new insight on TKIs resistance and immune escape. We found that patients with higher NOX4 and IL-8 expression levels showed a shorter survival time compared to those with lower NOX4 and IL-8 expression levels in response to the anti-PD-L1 therapy. Knockdown of NOX4, YY1 or IL-8 alone inhibited angiogenesis and tumor growth. Furthermore, the combination of NOX4 inhibitor GKT137831 and gefitinib had synergistic effect to inhibit cell proliferation and tumor growth and to increase cellular apoptosis. These findings demonstrated that NOX4 and YY1 were essential for mediating the acquired EGFR-TKIs resistance. IL-8 and PD-L1 are two downstream targets of NOX4 to regulate TKIs resistance and immunotherapy. These molecules may be used as potential new biomarkers and therapeutic targets for overcoming TKIs resistance in the future.

Complementary roles of EP2 and EP4 receptors in malignant glioma.

BACKGROUND AND PURPOSE: Glioblastoma (GBM) is the most aggressive brain tumour in the central nervous system, but the current treatment is very limited and unsatisfactory. PGE2 -initiated cAMP signalling via EP2 and EP4 receptors is involved in the tumourigenesis of multiple cancer types. However, whether or how EP2 and EP4 receptors contribute to GBM growth largely remains elusive. EXPERIMENTAL APPROACH: We performed comprehensive data analysis of gene expression in human GBM samples and determined their expression correlations through multiple bioinformatics approaches. A time-resolved fluorescence energy transfer (TR-FRET) assay was utilized to characterize PGE2 -mediated cAMP signalling via EP2 and EP4 receptors in human glioblastoma cells. Using recently reported potent and selective small-molecule antagonists, we determined the effects of inhibition of EP2 and EP4 receptors on GBM growth in subcutaneous and intracranial tumour models. KEY RESULTS: The expression of both EP2 and EP4 receptors was upregulated and highly correlated with a variety of tumour-promoting cytokines, chemokines, and growth factors in human gliomas. Further, they were heterogeneously expressed in human GBM cells, where they compensated for each other to mediate PGE2 -initiated cAMP signalling and to promote colony formation, cell invasion and migration. Inhibition of EP2 and EP4 receptors revealed that these receptors might mediate GBM growth, angiogenesis, and immune evasion in a compensatory manner. CONCLUSION AND IMPLICATIONS: The compensatory roles of EP2 and EP4 receptors in GBM development and growth suggest that concurrently targeting these two PGE2 receptors might represent a more effective strategy than inhibiting either alone for GBM treatment.

MKRN2 knockout causes male infertility through decreasing STAT1, SIX4, and TNC expression.

Makorin-2 (Mkrn2) is an evolutionarily conserved gene whose biological functions are not fully known. Although recent studies have shed insights on the potential causes of male infertility, its underlining mechanisms still remain to be elucidated. We developed a Mrkn2 knockout mice model to study this gene and found that deletion of Mkrn2 in mice led to male infertility. Interestingly, the expression level of signal transducer and activator of the transcription (STAT)1 was significantly decreased in MKRN2 knockout testis and MEF cells. Co-IP assay showed an interaction between MKRN2 and STAT1. Moreover, our results further indicated that MKRN2 regulated the expression level of SIX4 and tenascin C (TNC) via the EBF transcription factor 2 (EBF2) in mice. The results of our study will provide insights into a new mechanism of male infertility.

Studying spatial drug distribution in golf ball-shaped microspheres to understand drug release.

Poly (lactic-co-glycolic acid) (PLGA) microspheres have been one of the most successful products for slow drug release. While distribution of drugs in microspheres might be a fundamental factor affecting drug release, it has been often overlooked. Indeed, very few studies are available on the distribution of drugs in microspheres with complex morphology like golf ball-shaped microspheres. In this paper, the distribution of rotigotine in golf ball-shaped microspheres (GSRM) was investigated by argon ion milling, combined with scanning electron microscopy and energy dispersive X-ray spectroscopy (AIM-SEM-EDS). Rotigotine in GSRM was clearly observed in two forms, respectively in an aggregated state and as a molecular dispersion. The distribution of palmitic acid in the microspheres (used as an additive to reduce burst release) was also demonstrated: 10% was found on the microspheres' surface while 90% separated from the polymer to form small particles inside the microspheres onto which rotigotine aggregated through hydrogen bonding interactions. In in-vitro release studies we observed that first the phase-separated palmitic acid/rotigotine particles dissolved and released the drug, followed by the release of the molecularly dispersed rotigotines by osmosis. We also found that rotigotine accelerated the degradation and reduced the glass transition temperature of PLGA, which played an important role as well in the release of the drug from GSRM. Finally, two linear Level A in vitro-in vivo correlations were established and validated, indicating that the in vitro release testing could be a meaningful predictor for the in vivo performance of GSRM. Our work demonstrates the importance of studying drug distribution in complex microspheres to understand drug release.

Associating resistance to immune checkpoint inhibitors with immunological escape in colorectal cancer.

Colorectal cancer is a common malignant tumor that ranks third in incidence and second in mortality worldwide, and surgery in conjunction with chemotherapy and radiotherapy remains the most common treatment option. As a result of radiotherapy's severe side effects and dismal survival rates, it is anticipated that more alternatives may emerge. Immunotherapy, a breakthrough treatment, has made significant strides in colorectal cancer over the past few years, overcoming specialized therapy, which has more selectivity and a higher survival prognosis than chemoradiotherapy. Among these, immune checkpoint inhibitor therapy has emerged as the primary immunotherapy for colorectal cancer nowadays. Nonetheless, as the use of immune checkpoint inhibitor has expanded, resistance has arisen inevitably. Immune escape is the primary cause of non-response and resistance to immune checkpoint inhibitors. That is the development of primary and secondary drug resistance. In this article, we cover the immune therapy-related colorectal cancer staging, the specific immune checkpoint inhibitors treatment mechanism, and the tumor microenvironment and immune escape routes of immunosuppressive cells that may be associated with immune checkpoint inhibitors resistance reversal. The objective is to provide better therapeutic concepts for clinical results and to increase the number of individuals who can benefit from colorectal cancer immunotherapy.

Corrigendum: Regulation of microrna-497-targeting AKT2 influences tumor growth and chemoresistance to cisplatin in lung cancer.

[This corrects the article DOI: 10.3389/fcell.2020.00840.].

Discovery of a New CDK4/6 and PI3K/AKT Multiple Kinase Inhibitor Aminoquinol for the Treatment of Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is a lethal malignancy lacking effective treatment. The Cyclin-dependent kinases 4/6 (CDK4/6) and PI3K/AKT signal pathways play pivotal roles in carcinogenesis and are promising therapeutic targets for HCC. Here we identified a new CDK4/6 and PI3K/AKT multi-kinase inhibitor for the treatment of HCC. Methods: Using a repurposing and ensemble docking methodology, we screened a library of worldwide approved drugs to identify candidate CDK4/6 inhibitors. By MTT, apoptosis, and flow cytometry analysis, we investigated the effects of candidate drug in reducing cell-viability,inducing apoptosis, and causing cell-cycle arrest. The drug combination and thermal proteomic profiling (TPP) method were used to investigate whether the candidate drug produced antagonistic effect. The in vivo anti-cancer effect was performed in BALB/C nude mice subcutaneously xenografted with Huh7 cells. Results: We demonstrated for the first time that the anti-plasmodium drug aminoquinol is a new CDK4/6 and PI3K/AKT inhibitor. Aminoquinol significantly decreased cell viability, induced apoptosis, increased the percentage of cells in G1 phase. Drug combination screening indicated that aminoquinol could produce antagonistic effect with the PI3K inhibitor LY294002. TPP analysis confirmed that aminoquinol significantly stabilized CDK4, CDK6, PI3K and AKT proteins. Finally, in vivo study in Huh7 cells xenografted nude mice demonstrated that aminoquinol exhibited strong anti-tumor activity, comparable to that of the leading cancer drug 5-fluorouracil with the combination treatment showed the highest therapeutic effect. Conclusion: The present study indicates for the first time the discovery of a new CDK4/6 and PI3K/AKT multi-kinase inhibitor aminoquinol. It could be used alone or as a combination therapeutic strategy for the treatment of HCC.

Discovery of vanoxerine dihydrochloride as a CDK2/4/6 triple-inhibitor for the treatment of human hepatocellular carcinoma.

BACKGROUND: Cyclin-dependent kinases 2/4/6 (CDK2/4/6) play critical roles in cell cycle progression, and their deregulations are hallmarks of hepatocellular carcinoma (HCC). METHODS: We used the combination of computational and experimental approaches to discover a CDK2/4/6 triple-inhibitor from FDA approved small-molecule drugs for the treatment of HCC. RESULTS: We identified vanoxerine dihydrochloride as a new CDK2/4/6 inhibitor, and a strong cytotoxicdrugin human HCC QGY7703 and Huh7 cells (IC50: 3.79 µM for QGY7703and 4.04 µM for Huh7 cells). In QGY7703 and Huh7 cells, vanoxerine dihydrochloride treatment caused G1-arrest, induced apoptosis, and reduced the expressions of CDK2/4/6, cyclin D/E, retinoblastoma protein (Rb), as well as the phosphorylation of CDK2/4/6 and Rb. Drug combination study indicated that vanoxerine dihydrochloride and 5-Fu produced synergistic cytotoxicity in vitro in Huh7 cells. Finally, in vivo study in BALB/C nude mice subcutaneously xenografted with Huh7 cells, vanoxerine dihydrochloride (40 mg/kg, i.p.) injection for 21 days produced significant anti-tumor activity (p < 0.05), which was comparable to that achieved by 5-Fu (10 mg/kg, i.p.), with the combination treatment resulted in synergistic effect. Immunohistochemistry staining of the tumor tissues also revealed significantly reduced expressions of Rb and CDK2/4/6in vanoxerinedihydrochloride treatment group. CONCLUSIONS: The present study isthe first report identifying a new CDK2/4/6 triple inhibitor vanoxerine dihydrochloride, and demonstrated that this drug represents a novel therapeutic strategy for HCC treatment.

Regulation of MicroRNA-497-Targeting AKT2 Influences Tumor Growth and Chemoresistance to Cisplatin in Lung Cancer.

BACKGROUND: MicroRNA-497 (miR-497) has been implicated in several cancers. Increasing studies demonstrate the role of AKT2 in cancers as an oncogene which is closely associated with tumor aggressiveness by enhancing cancer cell survival, migration and invasion However, miR-497/AKT2 axis in non-small cell lung cancer (NSCLC) remains unclear. METHODS: Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of miR-497 and its target gene. The function of miR-497 in lung cancer was investigated through in vitro and in vivo assays (cell proliferation assay, cell migration assay, colony formation assay, flow cytometry assay, immunoblotting and tumorigenesis assay). Luciferase reporter assay was conducted to confirm the target gene of miR-497. RESULTS: In this study, we found that miR-497 was significantly downregulated in tumor tissues and blood samples of lung cancer patients. To understand the potential mechanism of miR-497 in inhibiting tumor growth, we showed that miR-497 blocked the activation of AKT2 and regulated cell proliferation, cell migration, colony formation and increases chemosensitivity of H1299 cells to cisplatin by inhibiting AKT2. MiR-497 also inhibited tumor growth and suppressed expression of AKT2 at the protein and mRNA levels in mouse xenograft tumors. CONCLUSION: Taken together, our findings indicated that miR-497 suppresses the tumor growth by targeting AKT2, and the miR-497/AKT2 axis is a potential therapeutic target for NSCLC intervention.

Mass spectrometry assisted arginine side chains assignment of NMR resonances in natural abundance proteins.

Arginine side chains play critical roles in many protein-ligand interactions and enzyme catalysis. Unambiguous resonance assignment is a prerequisite for the nuclear magnetic resonance (NMR) spectroscopy studies of arginine side chains dynamics and hydrogen exchange properties from which one can expect to elucidate in more detail the roles of arginine residues in protein structure and function. Here we present a new mass spectrometry (MS)-based method for assigning the side-chain resonances of arginine residues in 2D 1H-15N NMR spectra. The method requires no additional isotopic labeling, and relies on knowledge of the amino acid sequence, the modification of the guanidino groups and liquid chromatography-mass spectrometry rather than the protein's structure or properties. Correlating the modification rates can connect cross-peak positions from NMR data with MS data to support resonances assignments. In the present work, we have extended our original application to natural abundance human ubiquitin to provide ε-NH assessments of three arginine for this well-studied protein.

Apigenin Inhibits IL-6 Transcription and Suppresses Esophageal Carcinogenesis.

Esophagus cancer is the seventh cause of cancer-related deaths globally. In this study, we analyzed interleukin 6 (IL-6) gene expression in human esophagus cancer patients and showed that IL-6 mRNA levels are significantly higher in tumor tissues and negatively correlated with overall survival, suggesting that IL-6 is a potential therapeutic target for esophagus cancer. We further demonstrated that apigenin, a nature flavone product of green plants, inhibited IL-6 transcription and gene expression in human esophagus cancer Eca-109 and Kyse-30 cells. Apigenin significantly and dose-dependently inhibited cell proliferation and promoted apoptosis while stimulating the cleaved PARP (poly ADP-ribose polymerase) (C-PARP) and caspase-8 expression. It suppressed VEGF (Vascular endothelial growth Factor) expression and tumor-induced angiogenesis. Pretreatment of cells with IL-6 could completely reverse apigenin-induced cellular changes. Finally, using a preclinical nude mice model subcutaneously xenografted with Eca-109 cells, we demonstrated the in vivo antitumor activity and mechanisms of apigenin. Taken together, this study revealed for the first time that apigenin is a new IL-6 transcription inhibitor and that inhibiting IL-6 transcription is one of the mechanisms by which apigenin exhibits its anticancer effects. The potential clinical applications of apigenin in treating esophagus cancer warrant further investigations.

LncRNA LINC00319 is associated with tumorigenesis and poor prognosis in glioma.

Glioma is one of the most universally diagnosed malignant tumors in the central nervous system with high mortality and morbidity in the world. Long non-coding long intergenic non-protein coding RNA 319 (LINC00319) exerts promoting function in diverse range of human carcinomas, but its detailed role in glioma remains to be investigated. This study aimed to investigate the potential role and regulatory mechanism of LINC00319 and also its clinical value in glioma. In our study, LINC00319 was expressed at high levels in glioma and closely associated with poor prognosis of patients with glioma, whose knockdown impaired cell proliferation, arrested cell cycle and induced cell apoptosis of glioma. In addition, high expression of high mobility group AT-hook 2 (HMGA2) was found in glioma which was also in positive relation to LINC00319 expression. Moreover, LINC00319 directly bound to TATA-box binding protein associated factor 1 (TAF1) and further regulated HMGA2. Finally, rescue assays verified that LIN00319 modulated the tumorigenesis of glioma by regulating HMGA2. The present research elucidated the function role and underlying mechanism of LINC00319 in glioma and exposed a new insight into the molecular-targeted therapy for glioma.

Suppression of miR-143 contributes to overexpression of IL-6, HIF-1α and NF-κB p65 in Cr(VI)-induced human exposure and tumor growth.

Hexavalent chromium [Cr(VI)] is a known occupational and environmental contaminant and carcinogen, but new mechanisms of Cr(VI)-induced carcinogenesis remain to be elucidated. In this study, we found that expression of miR-143 is decreased, whereas that of Interleukin 6 (IL-6) is increased in blood samples of Cr(VI)-exposing workers compared with corresponding unexposed workers. In addition, IL-6 was increased in human bronchial epithelial cells (BEAS-Cr) exposed to Cr(VI) compared with unexposed BEAS-2B cells. To further investigate the mechanisms by which Cr(VI) promotes these changes, we assessed the effects of miR-143 on gene expression and found that miR-143 suppressed expression of IL-6, HIF-1α and NF-κB p65, and that inhibiting miR-143 promoted expression of IL-6, HIF-1α and NF-κB p65. Interestingly, IL-6 regulated expression of HIF-1α, and HIF-1α transcriptionally regulated expression of IL-6. Experiments in animals showed that miR-143 inhibited tumor growth and angiogenesis by regulating IL-6/HIF-1α and downstream signaling pathways in vivo. These outcomes support the hypothesis that the miR-143/IL-6/HIF-1α pathway functions to regulate Cr(VI)-induced carcinogenesis.

CT-pathologic correlation in lung adenocarcinoma and squamous cell carcinoma.

Distinguishing lung adenocarcinoma from squamous cell carcinoma (SCC) is clinically important. Computed tomography (CT) scan is an economical, effective, noninvasive, commonly available, and quick diagnostic way for lung cancer. In this study, we aim to compare the CT characteristics in adenocarcinoma and SCC.Data from 275 cases (259 adenocarcinoma and 16 SCC) were retrospectively compared. CT characteristics, including lesion size and shape, single/multifocal lesions, location of the tumor, the margin of lobes, whether the lesion had deep lobulated margin, bronchial cut-off sign, signs of dilated bronchial arteries, signs of vascular bundle thickening, signs of short burrs, spinous processes, and pleural indentation, were compared in 148 cases (137 adenocarcinoma and 11 SCC).Patients with adenocarcinoma were more likely to be female (44.2% vs 25.0%, P = .017). Compared with SCC, adenocarcinomas were more likely to have deep lobulated margin (81.0% vs 54.5%, P = .038), less likely to have smooth lobes margin (2.7% vs 83.3%, P < .001), more likely to have vascular bundle thickening (37.2% vs 0, P = .016) and pleural indentation (59.9% vs 18.2%, P = .01), and marginally less likely to have dilated bronchial arteries (17.5% vs 45.5%, P = .064). No significant difference was observed regarding to characteristics, including tumor size, location of the tumor, signs of bronchial cut-off, dilated bronchial arteries, short burrs, or spinous processes.CT scan has the potential to help to distinguish lung adenocarcinoma and SCC in a fast and commonly available way. CT could be a rough but fast way to diagnosis, and may thus shorten the waiting time to treatment and allow more time for clinicians, patients, and their families to prepare for future treatment.

A comparison of contrast-free MRA at 3.0T in cases of intracranial aneurysms with or without subarachnoid hemorrhage.

PURPOSE: To determine the diagnostic accuracy of contrast-free MRA at 3.0T for detection of intracranial aneurysms in patients with subarachnoid hemorrhage. METHODS: 411 patients (183 with SAH and 228 with non-SAH) underwent MRA. Accuracy, sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) were measured and compared with DSA. RESULTS: Except for a slight difference in sensitivity in patient-based and aneurysm-based evaluations (P=0.037), there were no other significant differences in accuracy, specificity, PPV, and NPV. CONCLUSION: VR 3D-TOF-MRA is a non-invasive approach with high accuracy in the diagnosis of intracranial aneurysms.

Diagnostic value of conventional MRI combined with DTI for neonatal hyperbilirubinemia.

BACKGROUND: Neonatal hyperbilirubinemia (NHB) is a common clinical disease and can cause bilirubin encephalopathy in severe cases. It is now widely accepted that increased signal intensity in the globus pallidus on MR T1WI is an important sign of neonatal bilirubin encephalopathy. And brain diffusion tensor imaging (DTI) has not been used extensively to study hyperbilirubinemia (HB). So we compared newborns with different hyperbilirubinemia of different severities and healthy newborns in order to determine the relationships among MRI signal intensities, serum bilirubin levels, and the molecular changes in brain water diffusion in hyperbilirubinemia. METHODS: Seventy-three newborns with hyperbilirubinemia were grouped into three groups: the mild increase group (M, 27 cases), the moderate increase group (O, 28 cases), and the severe group (S, 18 cases). The groups were based on serum bilirubin levels. We performed cranial MRI in these newborns, as well as 29 healthy full-term infants (group N). We compared and analyzed the mean signal values for the globus pallidus and the relationship between the bilirubin level and the score on the neonatal behavioral neurological assessment. Fifteen, 10, and 10 patients in groups M, O + S, and N were successfully examined using diffusion tensor imaging (DTI). We assessed the relationships among the signal from the globus pallidus, fractional anisotropy (FA), and average diffusion coefficient (DCav) of the posterior limb of the internal capsule (PLIC). RESULTS: There were significant differences in the mean signal value of bilateral globus pallidus between group O/S and group N [p = 0.029 and 0.000 (left), 0.038 and 0.000 (right)]. There were no significant differences in bilateral FA or DCav values between the patient groups and group N. The bilateral PLIC-FA and DCav values were significantly different between the patient groups and group N (P = 0.014 and 0.047, respectively). CONCLUSIONS: Increased signal intensity in the globus pallidus on T1-weighted imaging can be used as an objective index to evaluate neonatal bilirubin encephalopathy. Globus pallidus and PLIC injuries are likely to occur when the total serum bilirubin level is ≥20 mg/dl.

Meta-analysis of the IL23R and IL12B polymorphisms in multiple sclerosis.

PURPOSE: Polymorphisms in the genes encoding interleukin-23 receptor (IL23R) and the p40 subunit of IL-12/23 (IL12B) have been implicated in multiple sclerosis (MS) risk. However, results of different studies are inconsistent. Our aim was to perform a meta-analysis on this topic. METHODS: We assessed two variants (rs10889677 and rs7517847) of IL23R and the A1188C polymorphism (rs3212227) of IL12B. Electronic databases (PubMed, Web of Science and Scopus) were searched for eligible studies published until September 2014. Odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of association in dominant, recessive, homozygote and allelic comparison models. RESULTS: Seven case-control studies with 2250 MS patients and 2320 controls were included in this meta-analysis. The pooled results showed no association of rs10889677 and rs7517847 with MS risk in any of the genetic models. Although the pooled analysis showed an association between rs3212227 and MS in all study subjects in dominant (OR = 0.81, 95% CI: 0.66-0.99, P(h) = 0.480, P(z) = 0.044) and allelic comparison (OR = 0.84, 95% CI: 0.72-0.98, P(h) = 0.967, P(z) = 0.030) models, subgroup analysis based on ethnicity did not suggest an association between rs3212227 and MS risk in Caucasians in any of the genetic models, and there was no association between rs3212227 and MS risk in an Asian group. CONCLUSIONS: The IL23R polymorphisms rs10889677, rs7517847, and the IL12B polymorphism rs3212227 are not associated with MS risk.

Comparative analysis between 64- and 320-slice spiral computed tomography in the display of coronary artery stents and diagnosis of in-stent restenosis.

The aim of the present study was to compare the accuracy of 64-multi-slice spiral computed tomography (64-MSCT) and 320-MSCT in the display of coronary artery stents and diagnosis of in-stent restenosis. The data collected from the 64- and 320-MSCT coronary angiography of 93 patients following coronary artery stent implantation were retrospectively analyzed. The 64-MSCT group comprised 30 cases with 57 stents and the 320-MSCT group comprised 63 cases with 93 stents. The image quality, heart rate of the patients and the radiation effective dose (ED) they were subjected to, were compared. Furthermore, the diagnostic abilities of 64-and 320-MSCT coronary angiography for in-stent restenosis were evaluated using invasive coronary angiography results as the gold standards. Statistically significant differences were observed in the heart rate and ED of the patients from the two groups (P<0.05), but no significant difference was identified in the accuracy index (P>0.05). The sensitivity, specificity, positive and negative predictive value and accuracy of the 64-MSCT group were found to be 100% (7/7), 93.94% (31/33), 77.78% (7/9), 100% (31/31) and 95% (38/40), respectively, and those in the 320-MSCT group were found to be 100% (16/16), 95.89% (70/73), 84.21% (16/19), 100% (70/70) and 96.63% (86/89), respectively. The present findings suggest that both 64-MSCT and 320-MSCT can be used for follow-up and curative effect evaluation following coronary stent implantation; however, 320-MSCT has fewer requirements of the patients' heart rate and uses a lower radiation dose.