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Purposes: To systematically review and perform meta-analysis to evaluate the prognostic value of cervical nodal necrosis (CNN) on the staging computed tomography/magnetic resonance imaging (MRI) of nasopharyngeal carcinoma (NPC) in era of intensity-modulated radiotherapy., Methods: Literature search through PubMed, EMBASE, and Cochrane Library was conducted. The hazard ratios (HRs) with 95% confidence intervals (CIs) of CNN for distant metastasis-free survival (DMFS), disease free survival (DFS) and overall survival (OS) were extracted from the eligible studies and meta-analysis was performed to evaluate the pooled HRs with 95%CI., Results: Nine studies, which investigated the prognostic values of 6 CNN patterns on MRI were included. Six/9 studies were eligible for meta-analysis, which investigated the CNN presence/absence in any nodal group among 4359 patients. The pooled unadjusted HRs showed that the CNN presence predicted poor DMFS (HR =1.89, 95%CI =1.72-2.08), DFS (HR =1.57, 95%CI =1.08-2.26), and OS (HR =1.87, 95%CI =1.69-2.06). The pooled adjusted HRs also showed the consistent results for DMFS (HR =1.34, 95%CI =1.17-1.54), DFS (HR =1.30, 95%CI =1.08-1.56), and OS (HR =1.61, 95%CI =1.27-2.04). Results shown in the other studies analysing different CNN patterns indicated the high grade of CNN predicted poor outcome, but meta-analysis was unable to perform because of the heterogeneity of the analysed CNN patterns., Conclusion: The CNN observed on the staging MRI is a negative factor for NPC outcome, suggesting that the inclusion of CNN is important in the future survival analysis. However, whether and how should CNN be included in the staging system warrant further evaluation., (© 2022. The Author(s).)

Objectives: To propose and evaluate a convolutional neural network (CNN) algorithm for automatic detection and segmentation of mucosal thickening (MT) and mucosal retention cysts (MRCs) in the maxillary sinus on low-dose and full-dose cone-beam computed tomography (CBCT)., Materials and Methods: A total of 890 maxillary sinuses on 445 CBCT scans were analyzed. The air space, MT, and MRCs in each sinus were manually segmented. Low-dose CBCTs were divided into training, training-monitoring, and testing datasets at a 7:1:2 ratio. Full-dose CBCTs were used as a testing dataset. A three-step CNN algorithm built based on V-Net and support vector regression was trained on low-dose CBCTs and tested on the low-dose and full-dose datasets. Performance for detection of MT and MRCs using area under the curves (AUCs) and for segmentation using Dice similarity coefficient (DSC) was evaluated., Results: For the detection of MT and MRCs, the algorithm achieved AUCs of 0.91 and 0.84 on low-dose scans and of 0.89 and 0.93 on full-dose scans, respectively. The median DSCs for segmenting the air space, MT, and MRCs were 0.972, 0.729, and 0.678 on low-dose scans and 0.968, 0.663, and 0.787 on full-dose scans, respectively. There were no significant differences in the algorithm performance between low-dose and full-dose CBCTs., Conclusions: The proposed CNN algorithm has the potential to accurately detect and segment MT and MRCs in maxillary sinus on CBCT scans with low-dose and full-dose protocols., Clinical Relevance: An implementation of this artificial intelligence application in daily practice as an automated diagnostic and reporting system seems possible., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Menkes disease (MD) is a rare X-linked connective tissue disorder of copper metabolism caused by pathogenic variant(s) in ATP7A gene. The aim of the present study is to determine the clinical characteristics and molecular basis of one patient with MD. Methods: One 10-month-old Chinese boy who met the clinical manifestations of MD was enrolled in this study. Whole genome sequencing (WGS) was performed in the patient in order to identify the variant(s), followed by Sanger sequencing. RNA sequencing (RNA-seq) from whole blood was subsequently applied to assess the effect of variant on transcription levels, and reverse transcriptase-polymerase chain reaction (RT-PCR) was performed for further validation. In addition, X chromosome inactivation (XCI) status of the patient's mother at the DNA level was measured by capillary electrophoresis. Results: The patient suffered from intermittent convulsions for more than 6 months, with psychomoto retardation and neurodegenerations. The patient also had curly hair, hypopigmented skin, cutis laxa, decreased muscle strength and hypotonia. MRI showed the intracranial arteries were tortuous with some "spiral" changes. The patient's serum ceruloplasmin level was low. WGS revealed one novel hemizygous variant, c.2627-501C > T (NM_000,052.7), located in the deep intronic sequence of ATP7A gene. Sanger sequencing confirmed that the variant was inherited from his mother. RNA-seq confirmed the variant itself, and identified a pseudo-exon inserted between exons 12 and 13 in mRNA of ATP7A . The sequencing results of RT-PCR from the patient confirmed this finding, while neither of his parents detected aberrant splicing. The Capillary electrophoresis results showed that the patient's mother had a skewed XCI. Conclusion: Our finding of the variant enlarges the variant spectrum in the ATP7A gene. This is a novel deep intronic variant which leads to the activation of a pseudo-exons in the ATP7A gene, and it demonstrates the usefulness of WGS combined with RNA-seq, in terms of revealing disease-causing variants in non-coding regions. Furthermore, the fact that the deep intronic variants cause disease by the activation of pseudo-exon inclusion indicates that in MD this might be an important mechanism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhi, Ai, Sheng, Yu, Shu, Yu, Yu, Li and Cai.)

Background: CCCH transcription factors are important zinc finger transcription factors involved in the response to biotic and abiotic stress and physiological and developmental processes. Barley (Hordeum vulgare) is an agriculturally important cereal crop with multiple uses, such as brewing production, animal feed, and human food. The identification and assessment of new functional genes are important for the molecular breeding of barley., Results: In this study, a total of 53 protein-encoding CCCH genes unevenly dispersed on seven different chromosomes were identified in barley. Phylogenetic analysis categorized the barley CCCH genes (HvC3Hs) into eleven subfamilies according to their distinct features, and this classification was supported by intron-exon structure and conserved motif analysis. Both segmental and tandem duplication contributed to the expansion of CCCH gene family in barley. Genetic variation of HvC3Hs was characterized using publicly available exome-capture sequencing datasets. Clear genetic divergence was observed between wild and landrace barley populations in HvC3H genes. For most HvC3Hs, nucleotide diversity and the number of haplotype polymorphisms decreased during barley domestication. Furthermore, the HvC3H genes displayed distinct expression profiles for different developmental processes and in response to various types of stresses. The HvC3H1, HvC3H2 and HvC3H13 of arginine-rich tandem CCCH zinc finger (RR-TZF) genes were significantly induced by multiple types of abiotic stress and/or phytohormone treatment, which might make them as excellent targets for the molecular breeding of barley., Conclusions: Overall, our study provides a comprehensive characterization of barley CCCH transcription factors, their diversity, and their biological functions., (© 2022. The Author(s).)

Purpose: To investigate and identify first-trimester fasting plasma glucose (FPG) is related to gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes in Shenzhen population., Methods: We used data of 48,444 pregnant women that had been retrospectively collected between 2017 and 2019. Logistic regression analysis was used to evaluated the associations between first-trimester FPG and GDM and adverse pregnancy outcomes, and used to construct a nomogram model for predicting the risk of GDM. The performance of the nomogram was evaluated by using ROC and calibration curves. Decision curve analysis (DCA) was used to determine the clinical usefulness of the first-trimester FPG by quantifying the net benefits at different threshold probabilities., Results: The mean first-trimester FPG was 4.62 ± 0.42 mmol/L. A total of 6998 (14.4%) pregnancies developed GDM.489(1.01%) pregnancies developed polyhydramnios, the prevalence rates of gestational hypertensive disorder (GHD), cesarean section, primary cesarean section, preterm delivery before 37 weeks (PD) and dystocia was 1130 (2.33%), 20,426 (42.16%), 7237 (14.94%), 2386 (4.93%), and 1865 (3.85%), respectively. 4233 (8.74%) of the newborns were LGA, and the number of macrosomia was 2272 (4.69%), LBW was 1701 (3.51%) and 5084 (10.49%) newborns had admission to the ICU, which all showed significances between GDM and non-GDM groups (all P < 0.05). The univariate analysis showed that first-trimester FPG was strongly associated with risks of outcomes including GDM, cesarean section, macrosomia, GHD, primary cesarean section, and LGA (all OR > 1, all P < 0.05), furthermore, the risks of GDM, primary cesarean section, and LGA was increasing with first-trimester FPG as early as it was at 4.19-4.63 mmol/L. The multivariable analysis showed that the risks of GDM (ORs for FPG 4.19-4.63, 4.63-5.11 and 5.11-7.0 mmol/L were 1.137, 1.592, and 4.031, respectively, all P < 0.05) increased as early as first-trimester FPG was at 4.19-4.63 mmol/L, and first-trimester FPG which was also associated with the risks of cesarean section, macrosomia and LGA (OR for FPG 5.11-7.0 mmol/L of cesarean section: 1.128; OR for FPG 5.11-7.0 mmol/L of macrosomia: 1.561; OR for FPG 4.63-5.11 and 5.11-7.0 mmol/L of LGA: 1.149 and 1.426, respectively, all P < 0.05) and with its increasing, the risks of LGA increased. Furthermore, the nomogram had a C-indices 0.771(95% CI: 0.763~0.779) and 0.770(95% CI:0.758~0.781) in training and testing validation respectively, which showed an acceptable consistency between the observed, validation and nomogram-predicted probabilities, the DAC curve analysis indicated that the nomogram had important clinical application value for GDM risk prediction., Conclusions: FPG in the first trimester was an independent risk factor for GDM which can be used as a screening test for identifying pregnancies at risk of GDM and adverse pregnancy outcomes., (© 2021. The Author(s).)

Background: Middle cerebral artery (MCA) occlusion is extremely common, especially unilateral artery, which can result in a significant incidence of cerebral infarction., Objective: To assess the value of whole-brain computed tomography perfusion (CTP) imaging combined with dynamic CT angiography (dCTA) in the evaluation of pial collateral circulation in patients with MCA occlusion., Methods: Whole-brain CTP and dCTA images were acquired in 58 patients with unilateral MCA occlusion. All patients were divided into three groups according to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral score (by CTA). The CTP parameters were analysed, including relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), relative mean transit time (rMTT), and relative time to peak (rTTP). Patients were followed up with the modified Rankin scale (mRS). All cases in this study were confirmed by DSA., Results: The CTP parameters of the MCA blood supply area on the affected side of patients with different degrees of stenosis were significantly different from those on the unaffected side. There are significant differences in the CTP parameters and openings of the Willis circle in patients with different degrees of stenosis. Significant differences were found in the number of patients with good prognosis., Conclusions: Whole-brain CT perfusion combined with dynamic CTA can structurally and functionally evaluate the establishment of pial collateral circulation and its effect on cerebral hemodynamic changes.

A high-quality plasmon-fiber cavity in a doubly resonant configuration can exhibit second-harmonic generation (SHG) with over 5 orders of magnitude enhancement compared to gold nanoparticles on a fused silica substrate. Through coupling to a fiber cavity with the proper diameter, a high-quality ( Q ≈ 160) resonance can be achieved in combination with a single gold nanoparticle. In a classical picture, where the incident electric field travels coherently Q times around the fiber during the nonlinear process, the high Q of the coupled mode aids in highly efficient SHG. We accomplish two feats: First, we analyze the Q factor dependence of the SHG efficiency, proving the expected Q 4 dependence and thus confirming coherent E-field amplification in the fiber cavity. Second, we carefully adjust the fiber size further and tune the plasmon response of a gold nanoparticle to a high- Q cavity mode. We make sure that the second harmonic wavelength is simultaneously in resonance with a higher order fiber cavity mode, fulfilling the doubly resonant condition. As a result, a giant SH response with conversion efficiency up to 1.6 × 10 -5 is detected upon a pump intensity of 5 × 10 8 W/cm 2 for 100 fs pump pulses around 840 nm incident wavelength. Additionally, the importance of the doubly resonant condition is proven by detuning the size of the fiber, which leads to a drastic drop in SHG efficiency. This disparity of the SHG efficiency can be observed even by eye, when monitoring the intensity changes of the visible SH light during detuning.

Primary liver cancer is one of the most prevalent and deadly cancers, which incidence continues to increase while treatment response remains poor; thus, in-depth understanding of tumour events is necessary to develop more effective therapies. Animal models for liver cancer are powerful tools to reach this goal. Over the past decade, our laboratory has established multiple oncogene transgenic zebrafish lines that can be robustly induced to develop liver cancer. Histological, transcriptomic and molecular analyses validate the use of these transgenic zebrafish as experimental models for liver cancer. In this review, we provide a comprehensive summary of our findings with these inducible zebrafish liver cancer models in tumour initiation, oncogene addiction, tumour microenvironment, gender disparity, cancer cachexia, drug screening and others. Induced oncogene expression causes a rapid change of the tumour microenvironment such as inflammatory responses, increased vascularisation and rapid hepatic growth. In several models, histologically-proven carcinoma can be induced within one week of chemical inducer administration. Interestingly, the induced liver tumours show the ability to regress when the transgenic oncogene is suppressed by the withdrawal of the chemical inducer. Like human liver cancer, there is a strong bias of liver cancer severity in male zebrafish. After long-term tumour progression, liver cancer-bearing zebrafish also show symptoms of cancer cachexia such as muscle-wasting. In addition, the zebrafish models have been used to screen for anti-metastasis drugs as well as to evaluate environmental toxicants in carcinogenesis. These findings demonstrated that these inducible zebrafish liver cancer models provide rapid and convenient experimental tools for further investigation of fundamental cancer biology, with the potential for the discovery of new therapeutic approaches.

Immune response which involves distinct immune cells is associated with prognosis of breast cancer. Nonetheless, less study have determined the associations of different types of immune cells with patient survival and treatment response. In this study, A total of 1,502 estrogen receptor(ER)-negative breast cancers from public databases were used to infer the proportions of 22 subsets of immune cells. Another 320 ER-negative breast cancer patients from Guangdong Provincial People's Hospital were also included and divided into the testing and validation cohorts. CD8 + T cells, CD4 + T cells, B cells, and M1 macrophages were associated with favourable outcome (all p <0.01), whereas Treg cells were strongly associated with poor outcome ( p = 0.005). Using the LASSO model, we classified patients into the stromal immunotype A and B subgroups according to immunoscores. The 10 years OS and DFS rates were significantly higher in the immunotype A subgroup than immunotype B subgroup. Stromal immunotype was identified as an independent prognostic indicator in multivariate analysis in all cohorts and was also related to pathological complete response(pCR) after neoadjuvant chemotherapy. The nomogram that integrated the immunotype and clinicopathologic features showed good predictive accuracy for pCR and discriminatory power. The stromal immunotype A subgroup had higher expression levels of immune checkpoint molecules (PD-L1, PD-1, and CTLA-4) and cytokines (IL-2, INF-γ, and TGF-β). In addition, patients with immunotype A and B diseases had distinct mutation signatures. Therefore, The stromal immunotypes could predict survival and responses of ER-negative breast cancer patients to neoadjuvant chemotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ji, Yuan, Gao, Xu, Yang, Yang, Zhang, Yang, Li, Zhu, Cheng, Wu and Wang.)

Ethnopharmacological Relevance: Panax ginseng C. A. Meyer is a valuable medicinal herb and "alternative" remedy for the prevention and treatment of depression. Dysfunction of connexin43 (Cx43)-gap junction in astrocytes is predisposed to the precipitation of depression. Ginsenoside Rg1 (Rg1), the main bioactive constituent extracted from ginseng, is efficacious in the management of depression by upregulating the content of Cx43. Our previous results indicated that pretreatment with Rg1 significantly improved Cx43-gap junction in corticosterone (CORT)-treated astrocytes. However, the antidepressant mechanism underlying how Rg1 upregulates Cx43-gap junction in astrocytes hasn't been proposed., Aim of the Study: To dissect the mechanisms of Rg1 controlling Cx43 levels in primary astrocytes., Methods: We examined the changes of the level of Cx43 mRNA, the degradation of Cx43, as well as the ubiquitin-proteasomal and autophagy-lysosomal degradation pathways of Cx43 followed by Rg1 prior to CORT in rat primary astrocytes isolated from prefrontal cortex and hippocampus. Furthermore, the recognized method of scrape loading/dye transfer was performed to detect Cx43-gap junctional function, an essencial indicator of the antidepressant effect., Results: Pretreatment with Rg1 could reverse CORT-induced downregulation of Cx43 biosynthesis, acceleration of Cx43 degradation, and upregulation of two Cx43 degradation pathways in primary astrocytes., Conclusion: The findings in the present study provide the first evidence highlighting that Rg1 increases Cx43 protein levels through the upregulation of Cx43 mRNA and downregulation of Cx43 degradation, which may be attributed to the effect of Rg1 on the ubiquitin-proteasomal and autophagy-lysosomal degradation pathways of Cx43., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Although stratifying individuals with respect to nasopharyngeal carcinoma (NPC) risk with Epstein-Barr virus-based markers is possible, the performance of diagnostic methods for detecting lesions among screen-positive individuals is poorly understood., Methods: The authors prospectively evaluated 882 participants aged 30 to 70 years who were enrolled between October 2014 and November 2018 in an ongoing, population-based NPC screening program and had an elevated NPC risk. Participants were offered endoscopy and magnetic resonance imaging (MRI), and lesions were identified either by biopsy at a follow-up endoscopy or further contact and linkage to the local cancer registry through December 31, 2019. The diagnostic performance characteristics of endoscopy and MRI for NPC detection were investigated., Results: Eighteen of 28 identified NPC cases were detected by both methods, 1 was detected by endoscopy alone, and 9 were detected by MRI alone. MRI had significantly higher sensitivity than endoscopy for NPC detection overall (96.4% vs 67.9%; P difference = .021) and for early-stage NPC (95.2% vs 57.1%; P = .021). The sensitivity of endoscopy was suggestively lower among participants who had previously been screened in comparison with those undergoing an initial screening (50.0% vs 81.2%; P = .11). The authors observed a higher overall referral rate by MRI versus endoscopy (17.3% vs 9.1%; P < .001). Cases missed by endoscopy had early-stage disease and were more commonly observed for tumors originating from the pharyngeal recess., Conclusions: MRI was more sensitive than endoscopy for NPC detection in the context of population screening but required the referral of a higher proportion of screen-positive individuals. The sensitivity of endoscopy was particularly low for individuals who had previously been screened., (© 2021 American Cancer Society.)

Background: Convolutional neural networks (CNNs) have the potential to automatically delineate primary nasopharyngeal carcinoma (NPC) on magnetic resonance imaging (MRI), but currently, the literature lacks a module to introduce valuable pre-computed features into a CNN. In addition, most CNNs for primary NPC delineation have focused on contrast-enhanced MRI. To enable the use of CNNs in clinical applications where it would be desirable to avoid contrast agents, such as cancer screening or intra-treatment monitoring, we aim to develop a CNN algorithm with a positional-textural fully-connected attention (FCA) module that can automatically delineate primary NPCs on contrast-free MRI., Methods: This retrospective study was performed in 404 patients with NPC who had undergone staging MRI. A proposed CNN algorithm incorporated with our positional-textural FCA module ( A proposed ) was trained on manually delineated tumours ( M 1st ) to automatically delineate primary NPCs on non-contrast-enhanced T2-weighted fat-suppressed (NE-T2W-FS) images. The performance of A proposed , three well-established CNNs, Unet ( A unet ), Attention-Unet ( A att ) and Dense-Unet ( A dense ), and a second manual delineation repeated to evaluate human variability ( M 2 nd ) were measured by comparing to the reference standard M 1 st to obtain the Dice similarity coefficient (DSC) and average surface distance (ASD). The Wilcoxon rank test was used to compare the performance of A proposed against A unet , A att , A dense and M 2 nd ., Results: A proposed showed a median DSC of 0.79 (0.10) and ASD of 0.66 (0.84) mm. It performed better than the well-established networks A unet [DSC =0.75 (0.12) and ASD =1.22 (1.73) mm], A att [DSC =0.75 (0.10) and ASD =0.96 (1.16) mm] and A dense [DSC =0.71 (0.14) and ASD =1.67 (1.92) mm] (all P<0.01), but slightly worse when compared to M 2 nd [DSC =0.81 (0.07) and ASD =0.56 (0.80) mm] (P<0.001)., Conclusions: The proposed CNN algorithm has potential to accurately delineate primary NPCs on non-contrast-enhanced MRI., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims-21-196). Dr. LMW reports this study was presented, in part, by the first author at the 19th International Cancer Imaging Society annual meeting, October 7-9 2019; Verona, Italy. Attending cost was covered partially by the Department of Imaging and Interventional Radiology of The Chinese University of Hong Kong. The other authors have no conflicts of interest to declare., (2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) is a serious infection caused by the new coronavirus severe acute respiratory syndrome coronavirus 2. The disease was first identified in December 2019 and has caused significant morbidity and mortality worldwide., Aim: To explore the clinical characteristics and treatments for COVID-19 in the Qinghai-Tibetan Plateau Area in China., Methods: We retrospectively analyzed the blood cell counts (neutrophils and lymphocytes), blood gas analysis, and thoracic computed tomography changes of patients from Qinghai Province before, during, and after treatment (January 23, 2020 to February 21, 2020). In addition, we summarized and analyzed the information of critical patients. All data were analyzed using SPSS 17.0 (SPSS Inc., Chicago, IL, United States). The quantitative and count variables are represented as the mean ± SD and n (%), respectively., Results: The main symptoms and signs of patients with COVID-19 were fever, dry cough, cough with phlegm, difficulty breathing, and respiratory distress with a respiration rate ≥ 30 times/min, finger oxygen saturation ≤ 93% in the resting state, and oxygenation index less than 200 but greater than 100 (after altitude correction). Eighteen patients with COVID-19, of whom three were critical, and the others were in a mild condition, were included. The main manifestations included fever, dry cough, and fatigue. Three patients developed difficulty breathing and had a fever. They were eventually cured and discharged. Adjuvant examinations showed one case with reduced white cell count (6%) (< 4 × 10 9 /L), six with reduced count of lymphocytes (33%) (< 0.8 × 10 9 /L), and one with abnormal blood glucose level. All 18 patients were discharged, and no death occurred., Conclusion: Our findings provide critical insight into assessing the clinical diagnosis and treatment for COVID-19 in the Tibetan plateau area., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

A positive aging phenomenon, that is, enhancement of the electroluminescence performance at the beginning of electrical aging, is commonly observed for the state-of-the-art perovskite light-emitting diodes (PeLEDs). The origins of positive aging could fundamentally interfere with those of the operational deterioration processes of PeLEDs (namely negative aging), bringing difficulty in analyzing the degradation mechanisms. This work decouples the positive and negative aging processes of PeLEDs by inserting a thin ionic liquid interlayer between the hole-injection layer and the perovskite layer. This interlayer inhibits ions migration by passivating the halogen vacancies of perovskite films and suppresses interfacial exciton quenching, enabling us to decouple the positive and negative aging processes of PeLEDs while increasing the device efficiency. Inserting an ionic liquid interlayer is also demonstrated to be effective for iodide-based PeLEDs and applicable with the use of other ionic liquids. Our work provides an ideal system for fundamental studies on the degradation mechanisms of PeLEDs.

Purpose: Convolutional neural networks (CNNs) show potential for delineating cancers on contrast-enhanced MRI (ce-MRI) but there are clinical scenarios in which administration of contrast is not desirable. We investigated performance of the CNN for delineating primary nasopharyngeal carcinoma (NPC) on non-contrast-enhanced images and compared the performance to that on ce-MRI., Materials and Methods: We retrospectively analyzed primary NPC in 195 patients using a well-established CNN, U-Net, for tumor delineation on the non-contrast-enhanced fat-suppressed (fs)-T2W, ce-T1W and ce-fs-T1W images. The CNN-derived delineations were compared to manual delineations to obtain Dice similarity coefficient (DSC) and average surface distance (ASD). The DSC and ASD on fs-T2W were compared to those on ce-MRI. Primary tumor volumes (PTVs) of CNN-derived delineations were compared to that of manual delineations., Results: The CNN for NPC delineation on fs-T2W images showed similar DSC (0.71 ± 0.09) and ASD (0.21 ± 0.48 cm) to those on ce-T1W images (0.71 ± 0.09 and 0.17 ± 0.19 cm, respectively) (p > 0.05), and lower DSC but similar ASD to ce-fs-T1W images (0.73 ± 0.09, p < 0.001; and 0.17 ± 0.20 cm, p > 0.05). The CNN overestimated PTVs on all sequences (p < 0.001)., Conclusion: The CNN showed promise for NPC delineation on fs-T2W images in cases where it is desirable to avoid contrast agent injection. The CNN overestimated PTVs on all sequences.

Objectives: A convolutional neural network (CNN) was adapted to automatically detect early-stage nasopharyngeal carcinoma (NPC) and discriminate it from benign hyperplasia on a non-contrast-enhanced MRI sequence for potential use in NPC screening programs., Methods: We retrospectively analyzed 412 patients who underwent T2-weighted MRI, 203 of whom had biopsy-proven primary NPC confined to the nasopharynx (stage T1) and 209 had benign hyperplasia without NPC. Thirteen patients were sampled randomly to monitor the training process. We applied the Residual Attention Network architecture, adapted for three-dimensional MR images, and incorporated a slice-attention mechanism, to produce a CNN score of 0-1 for NPC probability. Threefold cross-validation was performed in 399 patients. CNN scores between the NPC and benign hyperplasia groups were compared using Student's t test. Receiver operating characteristic with the area under the curve (AUC) was performed to identify the optimal CNN score threshold., Results: In each fold, significant differences were observed in the CNN scores between the NPC and benign hyperplasia groups (p < .01). The AUCs ranged from 0.95 to 0.97 with no significant differences between the folds (p = .35 to .92). The combined AUC from all three folds (n = 399) was 0.96, with an optimal CNN score threshold of > 0.71, producing a sensitivity, specificity, and accuracy of 92.4%, 90.6%, and 91.5%, respectively, for NPC detection., Conclusion: Our CNN method applied to T2-weighted MRI could discriminate between malignant and benign tissues in the nasopharynx, suggesting that it as a promising approach for the automated detection of early-stage NPC., Key Points: • The convolutional neural network (CNN)-based algorithm could automatically discriminate between malignant and benign diseases using T2-weighted fat-suppressed MR images. • The CNN-based algorithm had an accuracy of 91.5% with an area under the receiver operator characteristic curve of 0.96 for discriminating early-stage T1 nasopharyngeal carcinoma from benign hyperplasia. • The CNN-based algorithm had a sensitivity of 92.4% and specificity of 90.6% for detecting early-stage nasopharyngeal carcinoma.

Purpose: To study the dynamic changes in plasma Epstein-Barr virus (pEBV) DNA after radiotherapy in nasopharyngeal cancer (NPC)., Experimental Design: We conducted a randomized controlled trial of adjuvant chemotherapy versus observation in patients with NPC who had detectable pEBV DNA at 6 weeks post-radiotherapy. Randomized patients had a second pEBV DNA checked at 6 months post-randomization. The primary endpoint was progression-free survival (PFS)., Results: We prospectively enrolled 789 patients. Baseline post-radiotherapy pEBV DNA was undetectable in 573 (72.6%) patients, and detectable in 216 (27.4%) patients, of whom 104 (13.2%) patients were eligible for randomization to adjuvant chemotherapy ( n = 52) versus observation ( n = 52). The first post-radiotherapy pEBV DNA had a sensitivity of 0.48, specificity of 0.81, area under receiver-operator characteristics curve (AUC) of 0.65, false positive (FP) rate of 13.8%, and false negative (FN) rate of 14.4% for disease progression. The second post-radiotherapy pEBV DNA had improved sensitivity of 0.81, specificity of 0.75, AUC of 0.78, FP rate of 14.3%, and FN rate of 8.1%. Patients with complete clearance of post-radiotherapy pEBV DNA (51%) had survival superior to that of patients without post-radiotherapy pEBV DNA clearance (5-year PFS, 85.5% vs. 23.3%; HR, 9.6; P < 0.0001), comparable with patients with initially undetectable post-radiotherapy pEBV DNA (5-year PFS, 77.1%), irrespective of adjuvant chemotherapy or observation., Conclusions: Patients with NPC with detectable post-radiotherapy pEBV DNA who experienced subsequent pEBV DNA clearance had superior survival comparable with patients with initially undetectable post-radiotherapy pEBV DNA. Post-radiotherapy pEBV DNA clearance may serve as an early surrogate endpoint for long-term survival in NPC., (©2021 American Association for Cancer Research.)

Purpose: T1rho imaging is a new quantitative MRI sequence for head and neck cancer and the repeatability for this region is unknown. This study aimed to evaluate the repeatability of quantitative T1rho imaging in the head and neck., Materials and Methods: T1rho imaging of the head and neck was prospectively performed in 15 healthy participants on three occasions. Scan 1 and 2 were performed with a time interval of 30 minutes (intra-session) and scan 3 was performed 14 days later (inter-session). T1rho values for normal tissues (parotid glands, palatine tonsils, pterygoid muscles, and tongue) were obtained on each scan. Intra-class coefficients (ICCs), within-subject coefficient of variances (wCoVs), and repeatability coefficient (RCs) of the intra-session scan (scan 1 vs 2) and inter-session scan (scan 1 vs 3) for the normal tissues were calculated., Results: The ICCs of T1rho values for normal tissues were almost perfect (0.83-0.97) for intra-session scans and were substantial (0.71-0.80) for inter-session scans. The wCoVs showed a small range (2.46%-3.30%) for intra-session scans, and slightly greater range (3.27%-6.51%) for inter-session scan. The greatest and lowest wCoVs of T1rho were found in the parotid gland and muscles, respectively. The T1rho RCs varied for all tissues between intra- and inter- sessions, and the greatest RC of 10.07 msec was observed for parotid gland on inter-session scan., Conclusion: T1rho imaging is a repeatable quantitative MRI sequence in the head and neck but variances of T1rho values among tissues should be take into account during analysis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALToma) arises in extranodal sites in the head and neck. Chronic inflammatory, infectious or autoimmune conditions are implicated in its pathogenesis. Within the head and neck, MALToma is often multifocal and indolent and the imaging appearances may be mistaken for non-malignant disease in the head and neck. The aim of this article is to illustrate the varied radiological and clinical features of MALToma in the head and neck, an awareness of which is needed for timely and correct diagnosis to guide subsequent disease management.

Ethnopharmacological Relevance: Kanglaite (KLT) is an active extract of the Coix lacryma-jobi seed, which can benefit Qi and nourish Yin, and disperse the accumulation of evils. It is used as a biphasic broad-spectrum anti-cancer drug, and shows synergistic effects with radiotherapy and chemotherapy. However, the mechanism of KLT combined with cisplatin (CDDP) against hepatocellular carcinoma (HCC) has not been elucidated., Aim of the Study: The aim of present study was to investigate the potential synergistic effects of KLT and CDDP on HepG2 cells, discussing the possible mechanisms from the perspective of CKLF1 and NF-κB mediated inflammatory response and chemoresistance, and the involvement of drug efflux transporters., Materials and Methods: CDDP injured HepG2 cells were used to investigate the effects of KLT on chemotherapeutics treated HCC. Effects of KLT pretreatment on CDDP injured HepG2 cells were determined by MTT, wound healing assay, and transwell assay. Expression of chemokine-like factor 1 (CKLF1) and activation of nuclear factor κB (NF-κB) were examined by qPCR, western blot, and immunofluorescence staining. Furthermore, to study the role of CKLF1 in KLT mediated effects on this CDDP injured HCC cell model, HepG2 cells overexpressed with CKLF1 gene were used. Cell viability and NF-κB activation were investigated. Moreover, TNF-α and IL-1β levels were measured by Elisa analysis and western blot to evaluate the inflammatory response. Additionally, ATP-binding cassette (ABC) drug efflux transporters, MDR1, MRP2, and BCRP were also determined in present study., Results: KLT pretreatment followed by CDDP treatment was found to show synergistic effects, which showed by decreased cell viability, migration and invasion ability of HepG2 cells. Expression of CKLF1 enhanced significantly in CDDP treated HepG2 cells, and KLT decreased this elevation obviously. Furthermore, CDDP activated NF-κΒ and promoted translocation of NF-κB toward the nucleus. KLT inhibited the activation of NF-κΒ, which sensitized cancer cells. Overexpression of CKLF1 reversed the effects of KLT on CDDP injured HepG2 cells, which exhibited by increased cell viability and enhanced activation of NF-κΒ. CDDP induced NF-κΒ activation could also lead to excessive inflammatory response, and KLT can suppress the aggravating inflammation which may be beneficial for tumor progression. Furthermore, we found that ABC drug efflux transporters MDR1, MRP2, and BCRP in CDDP treated HepG2 cells were decreased when pretreated with KLT., Conclusions: KLT pretreatment may increase the effects of CDDP on HepG2 cells, by exhibiting cooperative effects on suppression of HepG2 cells. The mechanisms may partly by inhibiting CKLF1 mediated NF-κB pathway, which may contribute to inflammation of tumor microenvironment and chemoresistance of CDDP. Inhibition of transporter-mediated drug efflux is also involved in KLT mediated sensitization effects of CDDP., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To compare the spectral computed tomography (CT) imaging parameters between squamous cell carcinoma (SCC) and adenocarcinoma (AC) at the gastroesophageal junction (GEJ)., Methods: A total of 80 patients were enrolled in this retrospective study. Among them, 35 were diagnosed with SCC (SCC group) and 45 were diagnosed with AC (AC group). All patients underwent an enhanced scan with spectral CT. The following CT imaging parameters were evaluated: iodine concentration (IC), water content (WC), effective atomic number (Eff-Z) and slope of the spectral HU curve (λHU) of lesions. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of spectral CT imaging parameters for diagnosis of SCC and AC., Results: Patients with SCC had lower IC, Eff-Z, and λHU in arterial phase and venous phase compared with AC (p< 0.05). There were no significant differences in WC between the two groups. ROC curve analyses revealed that IC, Eff-Z, and λHU in arterial phase and venous phase were predictors for diagnosis of SCC and AC (AUC > 0.5). Moreover, the IC, Eff-Z and λHU in venous phase had better differential diagnostic performances than that in arterial phase., Conclusions: Spectral CT could be useful in the differential diagnosis of SCC and AC at the GEJ. Therefore, a routine spectral CT scan is recommended for patients with carcinoma of the GEJ.

Purpose: Anatomical imaging criteria for the diagnosis of malignant head and neck nodes may not always be reliable. This study aimed to evaluate the diagnostic value of conventional diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) DWI in discriminating benign and malignant metastatic retropharyngeal nodes (RPNs)., Methods: IVIM DWI using 14 b-values was performed on RPNs of 30 patients with newly diagnosed metastatic nasopharyngeal carcinoma (NPC) and 30 patients with elevated plasma Epstein-Barr virus (EBV)-DNA without NPC who were part of an EBV-based NPC screening program. Histogram measurements of the two groups were compared for pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion volume fraction (f) and apparent diffusion coefficient (ADC) using the Mann-Whitney U test. Area under the curves (AUCs) of significant measurements were calculated from receiver-operating characteristics analysis and compared using the DeLong test., Results: Compared with metastatic RPNs, benign RPNs had lower ADC mean (0.73 vs 0.82 × 10 -3  mm 2 /s) and D mean (0.60 vs 0.71 × 10 -3  mm 2 /s) and a higher D* mean (35.21 vs 28.66 × 10 -3  mm 2 /s) (all p < 0.05). There was no difference in the f measurements between the two groups (p = 0.204 to 0.301). D mean achieved the highest AUC of 0.800, but this was not statistically better than the AUCs of the other parameters (p = 0.148 to 0.991)., Conclusion: Benign RPNs in patients with EBV-DNA showed greater restriction of diffusion compared with malignant metastatic RPNs from NPC. IVIM did not show a significant advantage over conventional DWI in discriminating benign and malignant nodes.

Objective: To investigate the value of pre-treatment amide proton transfer-weighted (APTw) imaging for predicting survival of patients with nasopharyngeal carcinoma (NPC)., Materials and Methods: Pre-treatment APTw imaging was performed in 77 NPC patients and the mean, 90th percentile, skewness, and kurtosis of APT asymmetry (APT mean , APT 90 , APT skewness , and APT kurtosis , respectively) were obtained from the primary tumor. Associations of APTw parameters with locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) after 2 years were assessed by univariable Cox regression analysis and significant APTw parameters, together with age, sex, treatment, and stage as confounding variables, were added to the multivariable model. Kaplan-Meier analysis was used to determine the prognostic significance of patients with high or low APT values based on a threshold value from receiver operating characteristic curve analysis., Results: Locoregional relapse, distant metastases, and disease relapse occurred in 14/77 (18%), 10/77 (13%), and 20/77 (26%) patients, respectively, at a median follow-up of 48.3 (10.6-67.4) months. Univariable analysis showed significant associations of LRRFS with APT skewness (HR = 1.98; p = 0.034), DMFS with APT mean (HR = 2.44; p = 0.033), and APT 90 (HR = 1.93; p = 0.009), and DFS with APT mean (HR = 2.01; p = 0.016), APT 90 (HR = 1.68; p = 0.009), and APT skewness (HR = 1.85; p = 0.029). In multivariable analysis, the significant predictors for DMFS were APT 90 (HR = 3.51; p = 0.004) and nodal stage (HR = 5.95; p = 0.034) and for DFS were APT 90 (HR = 1.97; p = 0.010) and age (HR = 0.92; p = 0.014). An APT 90 ≥ 4.38% was associated with a significantly poorer DFS at 2 years than APT 90 < 4.38% (66% vs. 91%; HR = 4.01; p = 0.005)., Conclusion: APTw imaging may potentially predict survival in patients with NPC., Key Points: • APTw imaging may provide new markers to predict survival in nasopharyngeal carcinoma. • APT 90 is an independent predictor of distant metastases-free survival and disease-free survival. • The APT high group is at higher risk of disease relapse than the APT low group.

Aberrant epigenetic regulation is critically involved in the pathogenesis of nasopharyngeal carcinoma (NPC), where abnormal histone methylation can be found in polycomb repressive complex-2 (PRC2) related cancer gene loci. This study investigated some novel combinational strategies against NPC in vitro using PRC2-targeting agents as a backbone. PRC2 subunit proteins were overexpressed in over 70% of NPC tumors and enhancer of zeste homolog-2 (EZH2) expression correlated with more advanced T-stage. Basal expression of EZH2 and embryonic ectoderm development (EED) was higher in Epstein-Bar virus (EBV) + NPC cells than EBV - cells. Treatment with an EED inhibitor (EED226) led to reduced levels of H3K27me3 with minimal inhibitory effect on NPC cell growth. The combination of an EZH2 inhibitor (EPZ-6438) and trichostatin-A (TSA) yielded the highest synergy score (12.64) in NPC cells in vitro than combinations using EED226 and agents like chemotherapy and azacitadine. Global gene expression analysis showed that EED226 predominantly affects the expression of major histocompatibility complex (MHC) class I genes and cell cycle-related genes in NPC cells. Furthermore, treatment with EED226 resulted in increased MHC-I proteins in vitro . Based on the prediction of an artificial neural network, a synergistic inhibitory effect on growth was found by combining EED226 with cyclin dependent kinase (CDK) 4/6 inhibitor (LEE011) in NPC cells. In summary, this study found that PRC2-targeting agents could exert synergistic effect on growth inhibition when combined with TSA or LEE011 in NPC cells. Since MHC-I genes alterations are found in a third of NPC tumors, the effect of EED226 on MHC-I genes expression on response to immunotherapy in NPC warrants further investigations., Competing Interests: None., (AJCR Copyright © 2020.)

Background: Chemokine-like factor 1 (CKLF1) is a chemokine increased significantly in ischemic brain poststroke. It shows chemotaxis effects on various immune cells, but the mechanisms of CKLF1 migrating neutrophils are poorly understood. Recent studies have provided evidence that CC chemokine receptor 5 (CCR5), a receptor of CKLF1, is involved in ischemic stroke., Purposes: To investigate the effects of HIF-1α guided AAV in ischemic brain, investigating the outcome of stroke, and examining the involvement of CKLF1/CCR5 axis in recruitment of neutrophils., Results: HIF-1α guided AAV knocked down CKLF1 in ischemic area and alleviated brain damage of rats. CKLF1 migrated neutrophils through CCR5, worsening inflammatory responses. Akt/GSK-3β pathway may involve in CKLF1/CCR5 axis guided neutrophils chemotaxis., Conclusions: CKLF1/CCR5 axis is involved in neutrophils migration of rats with transient cerebral ischemia. CKLF1/CCR5 axis may be a useful target for stroke therapy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: To evaluate whether pre-treatment intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can predict treatment outcome after 2 years in patients with nasopharyngeal carcinoma (NPC)., Method: One hundred and sixty-one patients with newly diagnosed NPC underwent pre-treatment IVIM-DWI. Univariate Cox regression analysis was performed to evaluate the correlation of the mean values of the pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction and apparent diffusion coefficient with local relapse-free survival (LRFS), regional relapse-free survival (RRFS), distant metastases-free survival (DMFS) and disease-free survival (DFS). Significant diffusion parameters, together with staging, age, gender and treatment as confounding factors, were added into a multivariate model. The area under the curves (AUCs) of significant parameters for disease relapse were compared using the Delong test., Results: Disease relapse occurred in 30 % of the patients at a median follow-up time of 52.1 months. The multivariate analysis showed that high D and T-staging were correlated with poor LRFS (p = 0.042 and 0.020, respectively) and poor DFS (p = 0.023 and 0.001, respectively); low D* and high T-staging with poor RRFS (p = 0.020 and 0.033, respectively); and high N-staging with poor DMFS (p = 0.006). D with the optimal threshold of ≥0.68 × 10 -3  mm 2 /s and T-staging showed similar AUCs (AUC = 0.614 and 0.651, respectively; p = 0.493) for predicting disease relapse., Conclusion: High D and low D* were predictors of poor locoregional outcome but none of the diffusion parameters predicted DMFS in NPC., Competing Interests: Declaration of Competing Interest The authors of this manuscript declare no financial or other conflicts of interest with the publication of this work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Triplet excitons can be effectively harvested in organic light-emitting diodes employing thermally activated delayed fluorescence (TADF) molecules as the emitter and host. A design strategy for blue and green emitters with small S 1 -T 1 splitting (Δ E ST ) is to construct a donor-acceptor (D-A) type molecule with moieties combining a high T 1 level with a strong electron-donating/withdrawing character. Here, we report a new kind of TADF emitter with an indolo[2,3- b ]indole (IDID) donor. In comparison to other reported indolocarbazole and indoloindole donors, IDID has a higher T 1 level, which is comparable to that of the classical donor 9,9-dimethyl-9,10-dihydroacridine (DMAC) for blue TADF emitters. The sky-blue and green TADF emitters based on the IDID donor and a phenyltriazine acceptor exhibit high photoluminescence quantum yields (0.78-0.92) and short TADF lifetimes (1.1-1.7 μs) in doped films. Devices employing these IDID-based emitters offer an external quantum efficiency of 19.2%, which is comparable to that obtained for a device employing an analogous compound with a DMAC donor, while the stability of the former is higher than that of the latter owing to the just-right D-A twisting angles (∼59°) in the IDID-based emitters leading to a balance between Δ E ST and the fluorescence rate. The utilization of host materials with a similar polarity to the emitter is found to be an effective strategy to improve device stability.

Introduction: MYH9-related disease (MYH9-RD) is a rare autosomal dominant disorder caused by mutations in MYH9, which is responsible for encoding nonmuscle myosin heavy chains IIA (NMMHCIIA). MYH9-RD is clinically characterized by congenital macrothrombocytopenia, granulocyte inclusions variably associated with the risk of developing progressive sensorineural deafness, cataracts and nephropathy., Patient Concerns: A 5-year-old boy had a history of a mild bleeding tendency and chronic thrombocytopenia, first identified at four months of age. No other family members were noted to have similar clinical features or hematologic disorders., Diagnoses: The boy was diagnosed with MYH9-RD. Light microscopic examination of peripheral blood films (Wright-Giemsa stain) showed marked platelet macrocytosis with giant platelets and basophilic Döhle-like inclusions in 83% of the neutrophils. Immunofluorescence analysis disclosed a type II pattern, manifested by neutrophils which contained several circle-to-oval shaped cytoplasmic NMMMHCA-positive granules. Sequencing analysis of MYH9-RD genes was carried out and revealed a novel missense mutation of c.97T>G (p.W33G) in the patient but not in his parents., Intervention: No treatment is necessary. Recognition of MYH9-RD is important to Avoiding unnecessary and potentially harmful treatments., Outcomes: The patient's condition remained stable during the follow-up., Conclusions: As a result of identifying this missense mutation in this particular case, we have added c.97T>G (p.W33G) to the broad spectrum of potential MYH9 mutations.

Objectives: To evaluate the effect of nutrition education on Chinese elite male young soccer players through the knowledge, attitude, behavior (KAP) survey and an adjusted dietary balance index (DBI)., Methods: 30 Chinese elite male young soccer players were randomly divided into two groups: lecture group (N = 15, Age: 16.7 ± 1.8 years, Height: 173.9 ± 9.0 cm; Weight: 62.4 ± 13.0 kg; Training years: 5.6 ± 2.7 years) and non-lecture group (N = 15, Age: 16.8 ± 1.7 years, Height: 175.5 ± 7.9 cm; Weight: 62.5 ± 12.3 kg; Training years: 6.2 ± 3.3). The comics book was given to the non-lecture group, while the a four-week nutritional quality education along with comic books were given to the lecture group. Before and after 4 weeks nutritional education, dietary nutritional status of both groups was assessed. The main outcome measurements included the scores for each part of the KAP survey, diet status (food-weighing method) and the dietary index in the adjusted DBI-07 system (DBI-low bound score, LBS; DBI-high bound score, HBS; and DBI-diet quality distance, DQD)., Results: In the lecture group, significant differences were found in the scores of general nutrition knowledge, sports nutrition knowledge and total scores of KAP dietary questionnaire after 4 weeks nutritional education (P < 0.01). However, there is no significant difference in dietary attitude and dietary behavior (P > 0.05) on both two groups. There is no significant change in the DBI-low bound score (LBS), DBI-high bound score (HBS) and DBI-diet quality distance (DQD) of dietary quality index (P > 0.05) in both two groups., Conclusions: Four weeks nutritional quality education improved the understanding of dietary nutrition among Chinese elite male young soccer players., (© 2019 The Society of Chinese Scholars on Exercise Physiology and Fitness. Published by Elsevier (Singapore) Pte Ltd.)

Objectives: MRI can detect early-stage nasopharyngeal carcinoma (NPC), but the detection is more challenging in early-stage NPCs because they must be distinguished from benign hyperplasia in the nasopharynx. This study aimed to determine whether intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI) MRI could distinguish between these two entities., Methods: Thirty-four subjects with early-stage NPC and 30 subjects with benign hyperplasia prospectively underwent IVIM DWI. The mean pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) values were calculated for all subjects and compared between the 2 groups using Student's t test. Receiver operating characteristics with the area under the curve (AUC) was used to identify the optimal threshold for all significant parameters, and the corresponding diagnostic performance was calculated. A p value of < 0.05 was considered statistically significant., Results: Compared with benign hyperplasia, early-stage NPC exhibited a significantly lower D mean (0.64 ± 0.06 vs 0.87 ± 0.11 × 10 -3  mm 2 /s), ADC 0-1000 mean (0.77 ± 0.08 vs 1.00 ± 0.13 × 10 -3  mm 2 /s), ADC 300-1000 (0.63 ± 0.05 vs 0.86 ± 0.10 × 10 -3  mm 2 /s) and a higher D* mean (32.66 ± 4.79 vs 21.96 ± 5.21 × 10 -3  mm 2 /s) (all p < 0.001). No significant difference in the f mean was observed between the two groups (p = 0.216). The D and ADC 300-1000 mean had the highest AUC of 0.985 and 0.988, respectively, and the D mean of < 0.75 × 10 -3  mm 2 /s yielded the highest sensitivity, specificity and accuracy (100%, 93.3% and 96.9%, respectively) in distinguishing early-stage NPC from benign hyperplasia., Conclusion: DWI has potential to distinguish early-stage NPC from benign hyperplasia and D and ADC 300-1000 mean were the most promising parameters., Key Points: • Diffusion-weighted imaging has potential to distinguish early-stage nasopharyngeal carcinoma from benign hyperplasia in the nasopharynx. • The pure diffusion coefficient, pseudo-diffusion coefficient from intravoxel incoherent motion model and apparent diffusion coefficient from conventional diffusion-weighted imaging were significant parameters for distinguishing these two entities in the nasopharynx. • The pure diffusion coefficient, followed by apparent diffusion coefficient, may be the most promising parameters to be used in screening studies to help detect early-stage nasopharyngeal carcinoma.

Inappropriate use of acetaminophen (APAP) can lead to morbidity and mortality secondary to hepatic necrosis. Ginsenoside Rg1 is a major active ingredient in processed Panax ginseng , which is proved to elicit biological effects. We hypothesized the beneficial effect of Rg1 on APAP-mediated hepatotoxicity was through Nrf2/ARE pathway. The study was conducted in cells and mice, comparing the actions of Rg1. Rg1 significantly improved cell survival rates and promoted the expression of antioxidant proteins. Meanwhile, Rg1 reduced the excessive ROS and the occurrence of cell apoptosis, which were related to Nrf2/ARE pathway. Expression of Nrf2 has a certain cell specificity.

CKLF1 is a chemokine with increased expression in ischemic brain, and targeting CKLF1 has shown therapeutic effects in cerebral ischemia model. Microglia/macrophage polarization is a mechanism involved in poststroke injury expansion. Considering the quick and obvious response of CKLF1 and expeditious evolution of stroke lesions, we focused on the effects of CKLF1 on microglial/macrophage polarization at early stage of ischemic stroke (IS). The present study is to investigate the CKLF1-mediated expression of microglia/macrophage phenotypes in vitro and in vivo, discussing the involved pathway. Primary microglia culture was used in vitro, and mice transient middle cerebral artery occlusion (MCAO) model was adopted to mimic IS. CKLF1 was added to the primary microglia for 24 h, and we found that CKLF1 modulated primary microglia skew toward M1 phenotype. In mice transient IS model, CKLF1 was stereotactically microinjected to the lateral ventricle of ischemic hemisphere. CKLF1 aggravated ischemic injury, accompanied by promoting microglia/macrophage toward M1 phenotypic polarization. Increased expression of pro-inflammatory cytokines and decreased expression of anti-inflammatory cytokines were observed in mice subjected to cerebral ischemia and administrated with CKLF1. CKLF1 -/- mice were used to confirm the effects of CKLF1. CKLF1 -/- mice showed lighter cerebral damage and decreased M1 phenotype of microglia/macrophage compared with the WT control subjected to cerebral ischemia. Moreover, NF-κB activation enhancement was detected in CKLF1 treatment group. Our results demonstrated that CKLF1 is an important mediator that skewing microglia/macrophage toward M1 phenotype at early stage of cerebral ischemic injury, which further deteriorates followed inflammatory response, contributing to early expansion of cerebral ischemia injury. Targeting CKLF1 may be a novel way for IS therapy.

Metal-free thermally activated delayed fluorescence (TADF) emitters have emerged as promising candidate materials for highly efficient and low-cost organic light-emitting diodes (OLEDs). Here, a novel acceptor 2-cyanopyrazine is selected for the construction of blue TADF molecules via computer-assisted molecular design. Both theoretical prediction and experimental photophysical data indicate a small S 1 -T 1 energy gap (Δ E ST ) and a relative large fluorescence rate ( k F ) in an o -phenylene-bridged 2-cyanopyrazine/3,6-di- tert -butylcarbazole compound (TCzPZCN). The k F value of 3.7 × 10 7 s -1 observed in a TCzPZCN doped film is among the highest in the TADF emitters with a Δ E ST smaller than 0.1 eV. Blue TADF emission is observed in a TCzPZCN doped film with a short TADF lifetime of 1.9 μs. The OLEDs using TCzPZCN as emitter exhibit a maximum external quantum efficiency (EQE) of 7.6% with low-efficiency roll-off. A sky-blue device containing a derivative of TCzPZCN achieves an improved EQE maximum of 12.2% by suppressing the non-radiative decay at T 1 .

Aim: To investigate microvascular changes in eyes with central retinal vein occlusion (CRVO) complicated by macular edema before and after intravitreal conbercept injection and evaluate correlations between these changes and best-corrected visual acuity (BCVA) and retinal thickness., Methods: Twenty-eight eyes of 28 patients with macular edema caused by CRVO were included in this retrospective study. All patients received a single intravitreal conbercept injection to treat macular edema. BCVA and the results of optical coherence tomography angiography (OCTA) automatic measurements of the vessel density in the superficial (SCP) and deep retinal capillary plexus (DCP), the foveal avascular zone (FAZ) area, the FAZ perimeter (PERIM), the vessel density within a 300-µm wide ring surrounding the FAZ (FD-300), the acircularity index (AI), the choriocapillaris flow area, and retinal thickness were recorded before and at one month after treatment and compared with the results observed in age- and sex-matched healthy subjects., Results: The vessel density in the SCP and DCP, the FD-300, and the flow area of the choriocapillaris were all significantly lower in CRVO eyes than in healthy eyes, while the AI and retinal thickness were significantly higher (all P <0.05). After treatment, retinal thickness was significantly decreased, and the mean BCVA had markedly improved from 20/167 to 20/65 ( P =0.0092). The flow area of the choriocapillaris was also significantly improved, which may result from the reduction of shadowing effect caused by the attenuation of macular edema. However, there were no significant changes in SCP and DCP vessel density after treatment. The flow area of the choriocapillaris at baseline was negatively correlated with retinal thickness., Conclusion: OCTA enables the non-invasive, layer-specific and quantitative assessment of microvascular changes both before and after treatment, and can therefore be used as a valuable imaging tool for the evaluation of the follow-up in CRVO patients.

Vascular dementia (VD) results from accumulated damage in the vascular system, which is characterized by progressive impairments in memory and cognition and is second only to Alzheimer's disease (AD) in prevalence among all types of dementia. In contrast to AD, there is no FDA-approved treatment for VD owing to its multiple etiologies. In this study, we investigated whether CZ-7, a new derivative of Claulansine F (Clau F) with verified neuroprotective activity in vitro, could ameliorate the cognitive impairment of rats with permanent occlusion of bilateral common carotid arteries (2VO) and its potential mechanisms of action. The 2VO rats were orally administered CZ-7 (10, 20, 40 mg/kg) from day 27 to day 53 post-surgery. Morris water maze tests conducted at day 48-51 revealed that CZ-7 administration significantly reduced the escape latency in 2VO rats. After the rats were sacrificed on day 53, morphological studies using Nissl and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining showed that administration of CZ-7 markedly attenuated the pathological changes in CA1-CA3 area of the hippocampus, including neuronal cell loss, nuclear shrinkage, and dark staining of neurons, and significantly decreased the chronic cerebral hypoperfusion-induced cell loss. Klüver-Barrera staining study revealed that CZ-7 administration significantly improved the white matter lesions. 8-OHdG and reactive oxygen species (ROS) immunofluorescent analyses showed that CZ-7 administration significantly decreased oxidative stress in CA1-CA3 area of the hippocampus. Finally, we found that the CZ-7-improved oxidative stress might be mediated via the Nrf2 pathway, evidenced by the double immunofluorescent staining of Nrf2 and the elevation of expression levels of oxidative stress proteins HO-1 and NQO1. In conclusion, CZ-7 has therapeutic potential for VD by alleviating oxidative stress injury through Nrf2-mediated antioxidant responses.

Purpose: To determine if treatment of nasopharyngeal carcinoma (NPC) induces early changes in amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI), and to perform a preliminary evaluation of APTw imaging in response assessment., Methods: Sixteen patients with NPC planned for treatment with radiotherapy and/or chemotherapy underwent APTw imaging of the primary tumour pre-treatment and 2-week intra-treatment. Difference in pre- and intra-treatment APT mean (APT mean ) was compared using the Wilcoxon signed rank test. Differences in APT mean and percentage change (%Δ) in APT mean were compared between responders and non-responders based on the outcome at 6 months, using the Mann-Whitney U test., Results: APT mean decreased in 9/16 (56.3%) and increased in 7/16 (43.7%) with no significant difference between the pre- and intra-treatment APT values for the whole group (p > 0.05). NPC showed response in 11/16 (68.8%) and non-response in 5/11 (31.2%). There were significant differences between the %Δ of responders and non-responders for APT mean (p = 0.01). Responders showed %Δ decrease in APT mean of - 23.12% while non-responders showed a %Δ increase in APT mean of + 102.28%., Conclusion: APT value changes can be detected in early intra-treatment. Intra-treatment %Δ APT mean shows potential in predicting short-term outcome.

As a vital cell type in immune system and infiltrating cells in ischemic brain, NK cells can bridge the crosstalk between immune system and nervous system in stroke setting. The mechanism of action of NK cells is complicated, involving direct and indirect actions. NK cells are closely associated with poststroke inflammation, immunodepression and infections. The excessive inflammatory response in ischemic brain is one of the important causes for aggravating cerebral ischemic injury. Besides the inflammation induced by ischemia itself, thrombolytic drug tissue plasminogen activator (tPA) administration could also induce deteriorative inflammation, which is unfavorable for stroke control and recovery. Regulating NK cells may has the potential to modulate the immune response, limiting the development of ischemic damage and getting better outcome. In addition, post-stroke immunosuppression may lead to infections which contribute to higher severity and mortality of ischemic stroke (IS). Targeting NK cells may help to find novel pathways for IS therapy, which can both ameliorate the infarction itself, but also reduce the infectious complications. NK cells may also link IS and related diseases, suggesting NK cells can be used as a diagnostic or prognostic biomarker for IS prevention and treatment., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Ginsenoside Rg1 (Rg1), a saponin extracted from Panax ginseng, has been well documented to be effective against ischemic/reperfusion (I/R) neuronal injury. However, the underlying mechanisms remain obscure. In the present study, we investigated the roles of Nrf2 and miR-144 in the protective effects of Rg1 against I/R-induced neuronal injury. In OGD/R-treated PC12 cells, Rg1 (0.01-1 μmol/L) dose-dependently attenuated the cell injury accompanied by prolonging nuclear accumulation of Nrf2, enhancing the transcriptional activity of Nrf2, as well as promoting the expression of ARE-target genes. The activation of the Nrf2/ARE pathway by Rg1 was independent of disassociation with Keap1, but resulted from post-translational regulations. Knockdown of Nrf2 abolished all the protective changes of Rg1 in OGD/R-treated PC12 cells. Furthermore, Rg1 treatment significantly decreased the expression of miR-144, which downregulated Nrf2 production by targeting its 3'-untranlated region after OGD/R. Knockdown of Nrf2 had no effect on the expression of miR-144, suggesting that miR-144 was an upstream regulator of Nrf2. We revealed that there was a direct binding between Nrf2 and miR-144 in PC12 cells. Application of anti-miR-144 occluded the activation of the Nrf2/ARE pathway by Rg1 in OGD/R-treated PC12 cells. In tMCAO rats, administration of Rg1 (20 mg/kg) significantly alleviated ischemic injury, and activated Nrf2/ARE pathway. The protective effects of Rg1 were abolished by injecting of AAV-HIF-miR-144-shRNA into the predicted ischemic penumbra. In conclusion, our results demonstrate that Rg1 alleviates oxidative stress after I/R through inhibiting miR-144 activity and subsequently promoting the Nrf2/ARE pathway at the post-translational level.

Purpose: Extranodal extension (ENE) is a criterion for advanced nodal staging of oropharyngeal and hypopharyngeal carcinoma. Our aim was to determine if ENE should be a staging criterion for nasopharyngeal carcinoma (NPC)., Materials & Methods: MRI of 546 NPC patients were reviewed retrospectively and in 404/546 (74.0%) with metastatic nodes, the nodes were assessed for ENE (grade 0 = absent; grade 1 = infiltration of surrounding fat; grade 2 = infiltration of muscle/skin), size (total volume), site (unilateral/bilateral and upper/lower neck) and necrosis. Associations between nodal features and regional relapse free survival (RRFS), distant metastases free survival (DMFS) and overall survival (OS) were assessed using cox regression. Differences of survival rates were compared using log-rank test. A p-value of < 0.05 indicates statistical significance., Results: ENE grade was the only determinant of RRFS (p = 0.014) and only independent determinant of DMFS (p = 0.003) and OS (p < 0.001). Grade 2 ENE was associated with significantly poorer RRFS, DMFS and OS compared to grade 0 and 1 (p < 0.05). Addition of grade 2 ENE to N1 and N2 disease showed similar poor RRFS, DMFS and OS to N3 disease (p > 0.05). Compared to the current stage N3 disease, inclusion of grade 2 ENE increased the number of N3 patients from 53/546 (9.7%) to 82/546 (15.0%) with similar hazard ratios for DMFS (6.855 and 7.125, respectively) and OS (3.614 and 4.085, respectively)., Conclusion: Grade 2 ENE (into muscle and/or skin and/or salivary glands) is an independent indicator of poor outcome and may be considered as a new criterion for N3 nodal disease in NPC., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We demonstrate second-harmonic generation with ultranarrow resonances in hybrid plasmon-fiber cavities, formed by depositing single-crystalline gold nanorods onto the surface of tapered microfibers with diameters in the range of 1.7-1.8 μm. The localized surface plasmon mode of the single gold nanorod efficiently couples with a whispering gallery mode of the fiber, resulting in a very narrow hybrid plasmon-fiber resonance with a high quality factor Q of up to 250. When illuminated with a tunable 100 fs laser, a sharp SHG peak narrower than half of the spectral width of the impinging laser emerges, superimposed on a broad multiphoton photoluminescence background. The enhancement of the SHG peak of the hybrid system is typically 1000-fold when compared to that of a single gold nanorod alone. Tuning the laser over the hybrid resonance enables second-harmonic spectroscopy and yields an ultranarrow line width as small as 6.4 nm. We determine the second-harmonic signal to rise with the square of the laser power, while the multiphoton photoluminescence background rises with powers between 4 and 6, indicating a very efficient higher-order process. A coupled anharmonic oscillator model is able to describe the linear as well as second-harmonic resonances very well. Our work will open the door to the simultaneous utilization of narrow whispering gallery resonances together with high plasmonic near-field enhancement and should allow for nonlinear sensing and extremely efficient nonlinear light generation from ultrasmall volumes.

Hypomotility is a common symptom of gallstone disease, which is accompanied by a loss of interstitial Cajal-like cells (ICLCs) in the gallbladder. Ursodeoxycholic acid (UDCA) is widely used in treating gallstone disease, and has shown anti-apoptotic and anti-inflammatory effects apart from its ability to dissolve gallstones. In this study, we investigated the anti-apoptotic and anti-inflammatory effects of UDCA on ICLCs in guinea pigs with gallstones. Guinea pigs were fed a high-cholesterol diet for 8 weeks to induce the formation of gallstones. A group of animals was administered UDCA (50 mg·kg -1 ·d -1 , ig) simultaneously. At the end of 8 weeks, the animals were euthanized with anesthesia, cholecystectomy was performed immediately and gallbladder was collected for further analysis. We showed that in the model group the contractility of gallbladder muscle strips in response to both acetylcholine (ACh) and CCK-8 was severely impaired, which was significantly improved by UDCA administration. Furthermore, UDCA administration significantly reduced the apoptotic ratio of ICLCs, based on the observation of co-localization imaging of apoptotic cells and c-kit-positive cells. Western blotting analysis and real-time PCR results revealed that the TNF-α/Caspase8/Caspase3 pathway was suppressed in the UDCA-treated animals, confirming the anti-apoptotic effect of UDCA in the gallbladder. The H&E staining showed that UDCA administration significantly attenuated inflammatory cell infiltration in the gallbladder wall. In conclusion, UDCA can protect ICLCs in the gallbladder from undergoing apoptosis by inhibiting the TNF-α/Caspase8/caspase3 pathway.

Purpose To evaluate the utility of amide proton transfer (APT) imaging in the characterization of head and neck tumors. Materials and Methods This retrospective study of APT imaging included 117 patients with 70 nasopharyngeal undifferentiated carcinomas (NUCs), 26 squamous cell carcinomas (SCCs), eight non-Hodgkin lymphomas (NHLs), and 13 benign salivary gland tumors (BSGTs). Normal tissues were examined in 25 patients. The APT means of malignant tumors, normal tissues, and benign tumors were calculated and compared with the Student t test and analysis of variance. The added value of the mean APT to the mean apparent diffusion coefficient (ADC) for differentiating malignant and benign tumors was evaluated by using receiver operating characteristic analysis and integrated discrimination index. Results The mean APT of malignant tumors (2.40% ± 0.97 [standard deviation]) was significantly higher than that of brain tissue (1.13% ± 0.43), muscle tissue (0.23% ± 0.73), and benign tumors (1.32% ± 1.20) (P < .001). There were no differences between malignant groups (NUC, 2.37% ± 0.90; SCC, 2.41% ± 1.16; NHL, 2.65% ± 0.89; P = .45 to P = .86). The mean ADC of malignant tumors ([0.85 ± 0.17] × 10 -3 mm 2 /sec) was significantly lower than that of benign tumors ([1.46 ± 0.47] × 10 -3 mm 2 /sec) (P = .001). Adding APT to ADC increased the area under the curve from 0.87 to 0.96, with an integrated discrimination index of 7.6% (P = .13). Conclusion These preliminary data demonstrate differences in amide proton transfer (APT) mean of malignant tumors, normal tissues, and benign tumors, although APT mean could not be used to differentiate between malignant tumor groups. APT imaging has the potential to be of added value to apparent diffusion coefficient in differentiating malignant from benign tumors., (© RSNA, 2018 Online supplemental material is available for this article.)

Currently, the research of chemokines has penetrated into many fields of life science. A new kind of chemokines, chemokine like factor 1 (CKLF1), which is cloned through suppression subtractive hybridisation (SSH) technology is expressed widely in human body, especially in the lung and peripheral blood leukocytes. CKLF1 has a broad spectrum of chemotaxic activity for many cells, such as lymphocytes, macrophages, bone marrow cells, nerve cells and so on. In addition, CKLF1 also stimulates the regeneration of skeletal muscle cells in vivo. Collecting data derived from our and other laboratories show that CKLF1 has an important relationship with allergic diseases, autoimmune diseases, tumors, cardio-cerebrovascular diseases and so on. Therefore, there be an important theoretical purport and applied value to make a summary of pharmacological progress of CKLF1., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To identify primary sites of nasopharyngeal carcinoma (NPC) invasion on the staging head and neck magnetic resonance imaging (MRI) that correlate with distant metastases (DM)., Materials and Methods: Staging head and neck MRI examinations of 579 NPC patients were assessed for primary tumour invasion into 16 individual sites, primary stage (T) and nodal stage (N). Results were correlated with distant metastasis-free survival (DMFS) using the Cox regression, and the diagnostic performance of significant independent markers for DM was calculated. In addition, sites of primary tumour invasion were correlated also with involvement of the first echelon of ipsilateral nodes (FEN+) using logistic regression., Results: Distant metastases were present in 128/579 NPC patients (22.1%) after intensity-modulated radiotherapy (IMRT)/chemo-IMRT and 5-year DMFS was 78.8%. Prevertebral space invasion (PVS+) and N stage, but not T stage, were independent prognostic markers of DMFS (p = 0.016, < 0.001, and 0.433, respectively). Compared to stage N3, PVS invasion had a higher sensitivity (28.1 vs. 68.8%), but lower specificity (90.5 vs. 47.4%) and accuracy (76.7 vs. 48.9%) for correlating patients with DM. PVS invasion, together with parapharyngeal fat space invasion (PPFS+), was also an independent predictive marker of FEN+., Conclusion: PVS was the only site of primary tumour invasion that independently correlated with DM, and together with PPFS + was an independent prognostic marker of FEN+, but the low specificity and accuracy of PVS invasion limits its use as a prognostic marker of DM.

Background and Purpose: Recently, the incidence of Parkinson's disease has shown a tendency to move to a younger population, linked to the constantly increasing stressors of modern society. However, this relationship remains obscure. Here, we have investigated the contribution of stress and the mechanisms underlying this change., Experimental Approach: Ten-month-old α-synuclein A53T mice, a model of Parkinson's disease (PD), were treated with chronic restraint stress (CRS) to simulate a PD-sensitive person with constant stress stimulation. PD-like behavioural tests and pathological changes were evaluated. Differentiated PC12-A53T cells were treated with corticosterone in vitro. We used Western blot, microRNA expression analysis, immunofluorescence staining, dual luciferase reporter assay and HPLC electrochemical detection to assess cellular and molecular networks after stress treatment. In vivo, stereotaxic injection of shRNA lentivirus was used to confirm our in vitro results., Key Results: The protein RTP801 is encoded by DNA-damage-inducible transcript 4, and it was specifically increased in dopaminergic neurons of the substantia nigra after CRS treatment. RTP801 was post-transcriptionally inhibited by the down-regulation of miR-7. Delayed turnover of RTP801, through the inhibition of proteasome degradation also contributed to its high content. Elevated RTP801 blocked autophagy, thus increasing accumulation of oligomeric α-synuclein and aggravating endoplasmic reticulum stress. RTP801 inhibition alleviated the symptoms of neurodegeneration during this process., Conclusions and Implications: RTP801 is a promising target for the treatment of PD, especially for PD-sensitive patients who live under increased social pressure. Down-regulation of RTP801 could inhibit the current tendency to an earlier onset of PD., (© 2017 The British Pharmacological Society.)

Background: The zygomatic implant is suggested to be placed in zygomatic areas with the largest thickness, but regions to obtain the largest bone-to-implant contact (BIC) were unknown., Purpose: To identify the zygomatic regions for placing quad zygomatic implants that obtain the largest BIC., Materials and Methods: The zygomatic thicknesses of 300 zygomata were measured at total 12 points on the superior, middle, and inferior areas on the 3-dimensional reconstruction images. In 50 edentulous maxillae, the zygomatic BICs of virtually placed implants were measured and the incidence of the intrusion into the infratemporal fossa calculated at each point., Results: The largest thickness in the superior, middle, and inferior regions were at Point A 1 (8.01 ± 2.10 mm), Point B 1 (7.02 ± 1.73 mm), and Point C 0 (6.65 ± 1.66 mm), respectively. The virtually placed implants at Point A 3 (16.70 ± 4.18 mm) and Point B 1 (12.07 ± 3.84 mm) had the highest BICs while retaining the minimum incidence of the intrusion complications., Conclusion: To obtain the largest BICs and avoid the intrusion complications, results suggested that the postero-superior region (Point A 3 ) and the center of zygoma (Point B 1 ) were the optimal places for the placement of quad zygomatic implants., (© 2017 Wiley Periodicals, Inc.)

We aim to evaluate the quantitative parameters of 18 F-FDG PET/CT (metabolic parameters) and MRI (morphologic parameters) for prognostication and risk stratification in nasopharyngeal carcinoma (NPC). 200 (147 males, aged 50 ± 13 years-old, mean ± S.D.) newly diagnosed patients with NPC (T x N x M 0 ) were prospectively recruited. Primary tumor and nodal lesions were identified and segmented for both morphologic (volume, VOL) and metabolic (SUV and MTV) quantification. Independent predictive factors for recurrence free survival (RFS) and overall survival (OS) were morphologic nodal volume (VOL&#95;N, p < 0.001), TNM-stage (p = 0.022), N-Stage (p = 0.024) for RFS, and VOL&#95;N (p = 0.014) for OS. Using Classification and Regression Tree (CART) analysis, three risk-layers were identified for RFS: Stage I/II with VOL&#95;N < 18cc (HR = 1), stage III /IV with VOL&#95;N < 18cc (HR = 2.93), VOL&#95;N ≥ 18cc (HR = 7.84) regardless of disease stage (p < 0.001). For OS, two risk layers were identified: VOL&#95;N < 18cc (HR = 1), VOL&#95;N ≥ 18cc (HR = 4.23) (p = 0.001). The 18cc threshold for morphologic nodal volume was validated by an independent cohort (n = 105). Based on the above risk-classification, 35 patients (17.5%) would have a higher risk than suggested by the TNM-staging system. Thus, morphologic nodal volume is an important factor in prognostication and risk stratification in NPC, and should be incorporated into the staging system, while PET parameters have no advantage for this purpose in our cohort.

Purpose: To determine if the magnetic resonance imaging (MRI) of the head and neck can predict distant metastases (DM) from nasopharyngeal carcinoma (NPC)., Methods and Materials: MRI examinations of 763 NPC patients were assessed for primary tumour stage (T), nodal stage (N), primary tumour volume (PTV) and total nodal volume (NV). The association between MRI and clinical parameters were examined in DM+ and DM- patients using logistic regression and for distant metastases free survival (DMFS) using cox regression. Optimum thresholds were assessed by receiver-operating characteristics analysis, and positive predictive value (PPV) and odds ratio (OR) calculated., Results: Distant metastases were present in 181/763 NPC patients (23.7%). Higher N stage and NV were the independent predictors of DM (p<0.001 and 0.018 respectively) and poor DMFS (p=0.001 and 0.030 respectively). Addition of NV (threshold≥32.8cm 3 ) to the N stage improved the PPVs and ORs for DM in stage N1 (from 18.9% to 31.8% and 5.613 to 11.133 respectively) and stage N2 (from 40.4% to 60.8% and 16.189 to 36.979 respectively) but not in stage N3 (68.3% to 68.6% and 51.385 to 52.052 respectively)., Conclusion: MRI N stage and NV were independent predictors of DM and DMFS. The addition of NV in NPC patients with bulky N1 and N2 disease improved the ability of MRI to predict DM., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To examine the effects of commercially available sports beverages with various components on substrate metabolism and subsequent performance. Methods: Two studies were conducted in a double-blinded, counterbalanced manner. Study I was designed to determine the glycemic index, while study II determined the utilization of substrates and subsequent exercise performance. Ten healthy male participants (age 21.70 ± 2.41 years, height 176.60 ± 5.23 cm, weight 66.58 ± 5.38 kg, V̇O 2max 48.1 ± 8.4 mL/kg/min) participated in both study I and study II. Three types of commercially available sports beverage powders were used. The powders consisted primarily of oligosaccharides (low molecular weight carbohydrates, L-CHO), hydrolyzed starch (high molecular weight CHO, H-CHO), and whey protein powder with carbohydrate (CHO-PRO). They were dissolved in purified water with identical CHO concentration of 8% ( w / v ). In study I, each participant underwent two oral glucose tolerance tests (OGTT) and one glycemic response test for each sports drink. In study II, participants cycled for 60 min at 70% V̇O 2max , one hour after consuming a standardized breakfast. One of four prescribed beverages (L-CHO, H-CHO, CHO-PRO, and Placebo control, PLA) was served at 0, 15, 30, 45 min during the exercise. Six hours after the first exercise session, participants came back for a "time to exhaustion test" (TTE). Blood samples were drawn at 0, 30, and 60 min in the first exercise session, while arterial blood gas analysis was conducted at 0, 30, and 60 min in both sessions. Subjective feelings (rating of perceived exertion and abdominal discomfort) were also evaluated every 30 min during exercise. Results: Compared to the reference standardized glucose solution, the glycemic index of the L-CHO beverage was 117.70 ± 14.25, while H-CHO was 105.50 ± 12.82, and CHO-PRO was 67.23 ± 5.88. During the exercise test, the insulin level at 30 and 60 min was significantly lower than baseline following the treatment of L-CHO, H-CHO, and PLA ( p < 0.05). The CHO oxidation rate at 60 min in the first exercise session was significantly higher than that at 60 min in the second exercise session following the L-CHO treatment ( p < 0.05). Time to exhaustion was not significantly different ( p > 0.05). Conclusion: The CHO sports beverage with additional PRO maintains insulin production during endurance cycling at 70% V̇O 2max in the postprandial state. L-CHO sports beverage suppresses fat utilization during the subsequent exercise performance test. The subsequent exercise performance (as evaluated by TTE) was not influenced by the type of CHO or the addition of PRO in the commercially available sports beverages used in the present study.