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SummaryTumor growth is manifestation of the evolution of a complex system. Researchers have limited scope of modelling studies on specific aspects or stages of the process. It has led to unsatisfactory explanation of clinical observations. We hereby demonstrated that an inhomogeneous model built on the generalized logistic equation could serve better. It was developed to describe the whole process of tumor progression, clinically observed independence of index tumor growth from spread of the disease and growth deceleration during early stage of solid tumors. It was validated by simulating the coexistence of exponential and sigmoidal growth in chronic lymphocytic leukaemia, theories of tumor heterogeneity, as well as by accommodating notions pertaining to tumor treatment and prognosis. We thought therefore it was an interesting and not unjustifiable description of actual tumor growth in human body and hoped it might encourage more researchers to look at tumor modelling from a clinical perspective.

Tetrabromobisphenol A (TBBPA) is an emerging persistent organic pollutant, which is very difficult to remove by common methods. In this study, the GO-load nanoscale zero-valent iron (NZVI/GO) was fabricated and optimized to improve the reaction rate and removal efficiency for TBBPA reliably and efficiently. The results showed that GO-load significantly reduced the self-aggregation of NZVI and the aggregate size decreased by 50.00% (1400-700 nm). Meanwhile, GO significantly improved the reaction rate k

Chronic suppurative otitis media (CSOM) and middle ear cholesteatoma (MEC) are the 2 most common chronic middle ear diseases. In the process of diagnosis and treatment, the 2 diseases are prone to misdiagnosis and missed diagnosis due to their similar clinical manifestations. High resolution computed tomography (HRCT) can clearly display the fine anatomical structure of the temporal bone, accurately reflect the middle ear lesions and the extent of the lesions, and has advantages in the differential diagnosis of chronic middle ear diseases. This study aims to develop a deep learning model for automatic information extraction and classification diagnosis of chronic middle ear diseases based on temporal bone HRCT image data to improve the classification and diagnosis efficiency of chronic middle ear diseases in clinical practice and reduce the occurrence of missed diagnosis and misdiagnosis.The clinical records and temporal bone HRCT imaging data for patients with chronic middle ear diseases hospitalized in the Department of Otorhinolaryngology, Xiangya Hospital from January 2018 to October 2020 were retrospectively collected. The patient's medical records were independently reviewed by 2 experienced otorhinolaryngologist and the final diagnosis was reached a consensus. A total of 499 patients (998 ears) were enrolled in this study. The 998 ears were divided into 3 groups: an MEC group (108 ears), a CSOM group (622 ears), and a normal group (268 ears). The Gaussian noise with different variances was used to amplify the samples of the dataset to offset the imbalance in the number of samples between groups. The sample size of the amplified experimental dataset was 1 806 ears. In the study, 75% (1 355) samples were randomly selected for training, 10% (180) samples for validation, and the remaining 15% (271) samples for testing and evaluating the model performance. The overall design for the model was a serial structure, and the deep learning model with 3 different functions was set up. The first model was the regional recommendation network algorithm, which searched the middle ear image from the whole HRCT image, and then cut and saved the image. The second model was image contrast convolutional neural network (CNN) based on twin network structure, which searched the images matching the key layers of HRCT images from the cut images, and constructed 3D data blocks. The third model was based on 3D-CNN operation, which was used for the final classification and diagnosis of the 3D data block construction, and gave the final prediction probability.The special level search network based on twin network structure showed an average AUC of 0.939 on 10 special levels. The overall accuracy of the classification network based on 3D-CNN was 96.5%, the overall recall rate was 96.4%, and the average AUC under the 3 classifications was 0.983. The recall rates of CSOM cases and MEC cases were 93.7% and 97.4%, respectively. In the subsequent comparison experiments, the average accuracy of some classical CNN was 79.3%, and the average recall rate was 87.6%. The precision rate and the recall rate of the deep learning network constructed in this study were about 17.2% and 8.8% higher than those of the common CNN.The deep learning network model proposed in this study can automatically extract 3D data blocks containing middle ear features from the HRCT image data of patients' temporal bone, which can reduce the overall size of the data while preserve the relationship between corresponding images, and further use 3D-CNN for classification and diagnosis of CSOM and MEC. The design of this model is well fitting to the continuous characteristics of HRCT data, and the experimental results show high precision and adaptability, which is better than the current common CNN methods.

Cancer stemness, mainly consisting of chemo-resistance, radio-resistance, tumorigenesis, metastasis, tumor self-renewal, cancer metabolism reprogramming, and tumor immuno-microenvironment remodeling, play crucial roles in the cancer progression process and has become the hotspot of cancer research field in recent years. Nowadays, the exact molecular mechanisms of cancer stemness have not been fully understood. Extensive studies have recently implicated that non-coding RNA (ncRNA) plays vital roles in modulating cancer stemness. Notably, N6-methyladenosine (m6A) modification is of crucial importance for RNAs to exert their biological functions, including RNA splicing, stability, translation, degradation, and export. Emerging evidence has revealed that m6A modification can govern the expressions and functions of ncRNAs, consequently controlling cancer stemness properties. However, the interaction mechanisms between ncRNAs and m6A modification in cancer stemness modulation are rarely investigated. In this review, we elucidate the recent findings on the relationships of m6A modification, ncRNAs, and cancer stemness. We also focus on some key signaling pathways such as Wnt/β-catenin signaling, MAPK signaling, Hippo signaling, and JAK/STAT3 signaling to illustrate the underlying interplay mechanisms between m6A modification and ncRNAs in cancer stemness. In particular, we briefly highlight the clinical potential of ncRNAs and m6A modifiers as promising biomarkers and therapeutic targets for indicating cancer stemness properties and improving the diagnostic precision for a wide variety of cancers.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. HCC has high rates of death and recurrence, as well as very low survival rates. N6-methyladenosine (m6A) is the most abundant modification in eukaryotic RNAs, and circRNAs are a class of circular noncoding RNAs that are generated by back-splicing and they modulate multiple functions in a variety of cellular processes. Although the carcinogenesis of HCC is complex, emerging evidence has indicated that m6A modification and circRNA play vital roles in HCC development and progression. However, the underlying mechanisms governing HCC, their cross-talk, and clinical implications have not been fully elucidated. Therefore, in this paper, we elucidated the biological functions and molecular mechanisms of m6A modification in the carcinogenesis of HCC by illustrating three different regulatory factors ("writer", "eraser", and "reader") of the m6A modification process. Additionally, we dissected the functional roles of circRNAs in various malignant behaviors of HCC, thereby contributing to HCC initiation, progression and relapse. Furthermore, we demonstrated the cross-talk and interplay between m6A modification and circRNA by revealing the effects of the collaboration of circRNA and m6A modification on HCC progression. Finally, we proposed the clinical potential and implications of m6A modifiers and circRNAs as diagnostic biomarkers and therapeutic targets for HCC diagnosis, treatment and prognosis evaluation.

N6-methyladenosine (m6A) modification regulators are essential for the diagnosis and treatment of various cancers. However, the comprehensive analysis about roles of m6A "readers" in hepatocellular carcinoma (HCC) remains unclear. UALCAN, GEPIA2, HPA, Kaplan Meier plotter, cBioPortal, STRING WebGestalt, Metascape and TIMER 2.0 database and Cytoscape software were used to comprehensively analyze the bioinformatic data. We found that m6A "readers" were upregulated at the mRNA level and protein level in HCC patients. Highly expressed YTHDF1, IGF2BP3 and NKAP were positively correlated with advanced HCC stage and had a poor prognosis in OS and PFS. The gene alterations of m6A "readers" happened frequently, and YTHDF3 had the highest mutation rate. The function of m6A "readers" on HCC may be closely correlated with splicing related proteins (including HNRNP family, SNRP family, and SR family), metabolic process, protein binding and RNA splicing related signaling pathways. Moreover, although the correlation of YTHDF3 and CD8+ T cell infiltration, and the correlation of IGF2BP3 and infiltration of mast cells and CAF are negative, most m6A "readers" had a positive correlation with immune cells (including CD8+ T cell, CD4+ T cell, Tregs, B cell, neutrophil, monocyte, macrophage, myeloid dendritic cell, nature killer cell, mast cell, and CAF). Macrophages, CD4+ T cell, Treg, B cell, monocyte, and myeloid dendritic cell had a positively strong correlation (Rhogt;0.4) with most m6A "readers" (such as YTHDC1, YTHDC2, YTHDF1, IGF2BP3, HNRNPA2B1 and HNRNPC). In conclusion, by comprehensive analysis of m6A "readers", we found that they were involved in the prognosis of HCC, and m6A "readers" might regulate the development and progression of HCC by participating in some metabolism-related and RNA splicing-related signaling pathways as well as immune cell infiltration.

The lncRNA tumor suppressor candidate 8 (TUSC8) plays a critical role in the development of several cancers. However, the biological functions and underlying molecular mechanisms of TUSC8 with respect to breast cancer remain largely unclear. Here, we found that TUSC8 was significantly down-regulated in breast cancer tissues and its high expression predicted better prognosis of breast cancer patients. Functionally, knock-down of TUSC8 drastically promoted the proliferation, migration and invasion of breast cancer cells in vitro and facilitated tumorigenicity and metastasis in vivo. Mechanistically, the results of luciferase reporter, RIP and RNA pull-down assays proved that TUSC8 functioned as molecular sponge for miR-190b-5p. Furthermore, we showed that TUSC8 served as a competing endogenous RNA (ceRNA) of myosin regulatory light chain interacting protein (MYLIP) through competitively binding with miR-190b-5p and suppressed breast cancer metastasis through regulating the expression of epithelial–mesenchymal transition (EMT) related markers. Clinically, the receiver operating characteristic curve (ROC) analyses revealed that the combination usage of TUSC8 and MYLIP might become novel promising diagnostic biomarkers for breast cancer. Taken together, these results suggested that TUSC8 inhibited breast cancer growth and metastasis via miR-190b-5p/MYLIP axis, providing us new insights into developing potential therapeutic targets for breast cancer patients.

The Objectives of this study are (1) to evaluate tone production in Mandarin-speaking patients with post-stroke dysarthria (PSD) using an artificial neural network (ANN), (2) to investigate the efficacy of recognition performance of the ANN model contrast to the human listeners and the convolutional neural network (CNN) model, and (3) to explore rehabilitation application of the artificial intelligence recognition for lexical tone production disorder with PSD. The subjects include two groups of native Mandarin speaking adults: 31 patients with PSD and 42 normal-speaking adults (NA) in a similar age range as controls. Each subject was recorded producing a list of 7 Mandarin monosyllables with 4 tones (i.e., a total of 28 tokens). The fundamental frequency (F0) of each monosyllable was extracted using auto-correlation algorithm. The ANN was trained with F0 data of the tone tokens from the NA, to generate the final model. The recognition rates of the human ears, ANN model, and CNN model were 87.78% ± 8.96% (mean ± SD), 89.11% ±11.80%, 65.91% ± 8.79% respectively for tone production of NA group; 70.28% ± 17.61%, 63.35% ± 17.40%, 34.71% ± 6.92% respectively for tone production of PSD group. For PSD group, there was significant correlation between the performance of the ANN model and human listeners (r = 0.826, P

Purpose: To explore the fever-related risk factors of inpatients in Rehabilitation Department, and to provide reference for patients with high risk of fever to take corresponding nursing measures. Methods: The study was conducted on the Rehabilitation Department of The First Affiliated Hospital of Jinan University from July 2019 to December 2019. The fever group included 51 patients and the non-fever group included 49 patients without fever. The two groups of clinical data, comorbidities, related laboratory values, possible risk factors of fever were analyzed by case regression analysis, and the relevant risk factors were screened out by LASSO (least absolute shrinkage and selection operator) regression analysis. Results: According to the results of Lasso regression analysis, pressure sore or skin infection, history of hypertension, current history of respiratory tract infection, feeding patterns were the higher risk factors of fever in inpatients in Rehabilitation Department, while the first course of disease, main diagnosis, history of respiratory tract infection within half a year, kidney damage and hospitalization days were lower risk factors. Conclusion: This study is helpful to early identify the fever risk of inpatients in Rehabilitation Department, and provide reference basis for high-risk fever patients to take positive and effective nursing measures.

To evaluate the effectiveness of machine learning models based on morphological magnetic resonance imaging (MRI) radiomics in the classification of parotid tumors.In total, 298 patients with parotid tumors were randomly assigned to a training and test set at a ratio of 7:3. Radiomics features were extracted from the morphological MRI images and screened using the Select K Best and LASSO algorithm. Three-step machine learning models with XGBoost, SVM, and DT algorithms were developed to classify the parotid neoplasms into four subtypes. The ROC curve was used to measure the performance in each step. Diagnostic confusion matrices of these models were calculated for the test cohort and compared with those of the radiologists.Six, twelve, and eight optimal features were selected in each step of the three-step process, respectively. XGBoost produced the highest area under the curve (AUC) for all three steps in the training cohort (0.857, 0.882, and 0.908, respectively), and for the first step in the test cohort (0.826), but produced slightly lower AUCs than SVM in the latter two steps in the test cohort (0.817 vs. 0.833, and 0.789 vs. 0.821, respectively). The total accuracies of XGBoost and SVM in the confusion matrices (70.8% and 59.6%) outperformed those of DT and the radiologist (46.1% and 49.2%).This study demonstrated that machine learning models based on morphological MRI radiomics might be an assistive tool for parotid tumor classification, especially for preliminary screening in absence of more advanced scanning sequences, such as DWI.• Machine learning algorithms combined with morphological MRI radiomics could be useful in the preliminary classification of parotid tumors. • XGBoost algorithm performed better than SVM and DT in subtype differentiation of parotid tumors, while DT seemed to have a poor validation performance. • Using morphological MRI only, the XGBoost and SVM algorithms outperformed radiologists in the four-type classification task for parotid tumors, thus making these models a useful assistant diagnostic tool in clinical practice.

Hepatocellular carcinoma (HCC) is one of the most lethal tumors in China and worldwide, although first-line therapies for HCC, such as atezolizumab and bevacizumab, have been effective with good results, the researches on new therapies have attracted much attention. With the deepening research on tumor immunology, the role and operation mechanism of immune cells in the tumor microenvironment (TME) of HCC have been explained, such as programmed cell death protein 1 (PD-1) binding to ligand could cause T cell exhaustion and reduce IFN-γ T cell secretion, cytotoxic T lymphocyte 4 (CTLA-4) and CD28 mediate immunosuppression by competing for B7 protein and disrupting CD28 signal transduction pathway, which also lays the foundation for the development and application of more new immune checkpoint inhibitors (ICIs). The biological behavior of various immune checkpoints has been proved in HCC, such as PD-1, programmed cell death ligand 1 (PD-L1), CTLA-4 and so on, leading to a series of clinical trials. Currently, FDA approved nivolumab, pembrolizumab and nivolumab plus ipilimumab for the treatment of HCC. However, the treatment of ICI has the disadvantages of low response rate and many side effects, so the combination of ICIs and various other therapies (such as VEGF or VEGFR inhibition, neoadjuvant and adjuvant therapy, locoregional therapies) has been derived. Further studies on immune checkpoint mechanisms may reveal new therapeutic targets and new combination therapies in the future.

Background. Due to the molecular heterogeneity of hepatocellular carcinoma (HCC), majority of patients respond poorly among various of therapy. This study is aimed at conducting a comprehensive analysis about roles of SOX family in HCC for obtaining more therapeutic targets and biomarkers which may bring new ideas for the treatment of HCC. Methods. UALCAN, Kaplan Meier plotter, cBioPortal, STRING, WebGestalt, Metascape, TIMER 2.0, DiseaseMeth, MethSurv, HPA, CCLE database, and Cytoscape software were used to comprehensively analyze the bioinformatic data. Results. SOX2, SOX4, SOX8, SOX10, SOX11, SOX12, SOX17, and SOX18 were significantly differentially expressed in HCC and normal tissues and were valuable for the grade and survival of HCC patients. In addition, the gene alterations of SOX family happened frequently, and SOX4 and SOX17 had the highest mutation rate. The function of SOX family on HCC may be closely correlated with the regulation of angiogenesis-related signaling pathways. Moreover, SOX4, SOX8, SOX11, SOX12, SOX17, and SOX18 were correlation with 8 types of immune cells (including CD8+ T cell, CD4+ T cell, B cell, Tregs, neutrophil, macrophage, myeloid DC, and NK cell), and we found that most types of immune cells had a positive correlation with SOX family. Notably, CD4+ T cell and macrophage were positively related with all these SOX family. NK cells were negatively related with most SOX family genes. DNA methylation levels in promoter area of SOX2, SOX4, and SOX10 were lower in HCC than normal tissues, while SOX8, SOX11, SOX17, and SOX18 had higher DNA methylation levels than normal tissues. Moreover, higher DNA methylation level of SOX12 and SOX18 demonstrated worse survival rates in patients with HCC. Conclusion. SOX family genes could predict the prognosis of HCC. In addition, the regulation of angiogenesis-related signaling pathways may participate in the development of HCC. DNA methylation level and immune microenvironment characteristics (especially CD4+ T cell and macrophage immune cell infiltration) could be a novel insight for predicting prognosis in HCC.

Epstein-Barr virus (EBV) and human papillomavirus (HPV) infection is the risk factors for nasopharyngeal carcinoma and cervical carcinoma, respectively. However, clinical analyses demonstrate that EBV or HPV is associated with improved response of patients, although underlying mechanism remains unclear. Here, we reported that the oncoproteins of DNA viruses, such as LMP1 of EBV and E7 of HPV, inhibit PERK activity in cancer cells via the interaction of the viral oncoproteins with PERK through a conserved motif. Inhibition of PERK led to increased level of reactive oxygen species (ROS) that promoted tumor and enhanced the efficacy of chemotherapy in vivo. Consistently, disruption of viral oncoprotein-PERK interactions attenuated tumor growth and chemotherapy in both cancer cells and tumor-bearing mouse models. Our findings uncovered a paradoxical effect of DNA tumor virus oncoproteins on tumors and highlighted that targeting PERK might be an attractive strategy for the treatment of NPC and cervical carcinoma.

Background To establish a radiomics nomogram for survival prediction and determine if genomic data were related to radiomics signature in advanced nasopharyngeal carcinoma (NPC). Methods Radiomics features were extracted from contrast-enhanced T1-weighted images (CE-T1WI) in 316 patients. A progression-free survival (PFS) nomogram was developed and validated by the combination of the radiomics signature and clinicopathologic factors. Whole transcriptomics sequencing was performed in pretreatment tumor samples; correlation of gene expression and radiomics signature was further investigated. Results A 24-feature-combined radiomics signature was highly correlated with PFS; its integration with clinical predictors showed good prediction performance in the training and the validation cohort (C-index: 0.80 and 0.73). A significant correlation was observed between certain gene expression and Rad-score, especially the mRNA expression of CDKL2, PLIN5, and SPAG1. Conclusion As a noninvasive method, the MRI-based radiomics signature might enable the pretreatment prediction of prognosis and gene expressions profile in advanced NPC.

Glioma is the most common intracranial primary tumor in central nervous system. Glioma grading possesses important guiding significance for the selection of clinical treatment and follow-up plan, and the assessment of prognosis. This study aims to explore the feasibility of logistic regression model based on radiomics to predict glioma grading.Retrospective analysis was performed on 146 glioma patients with confirmed pathological diagnosis from January, 2012 to December, 2018. A total of 41 radiomics features were extracted from contrast-enhanced TA total of 5 imaging features selected by LASSO were used to establish a logistic regression model for predicting glioma grading. The model showed good discrimination with AUC value of 0.919. Hosmer-Lemeshow test showed no significant difference between the calibration curve and the ideal curve (The logistic regression model using radiomics exhibits a relatively high accuracy for predicting glioma grading, which may serve as a complementary tool for preoperative prediction of giloma grading.

To explore whether radiomics features extracted from pre-treatment magnetic resonance imaging (MRI) can predict the overall survival (OS) in patients with hypopharyngeal squamous cell carcinoma. A total of 190 patients with hypopharyngeal squamous cell carcinoma were eligibly enrolled from two institutions. Radiomics features were extracted from contrast-enhanced axial T1-weighted (CE-T1WI) sequence. The least absolute shrinkage selection operator (LASSO) algorithm was applied to establish a radiomics score correlated with OS. Multivariate logistic regression analysis was applied to determine the independent risk factors, which was combined with radiomics score to build the final radiomics nomogram. A radiomics score with 6 CE-T1WI features for OS prediction was constructed and validated; its integration with specific clinicopathologic factors (N stage) showed a better prediction performance in the training, internal validation, and external validation cohorts (C-index 0.78, 0.75, and 0.75). Calibration curves determined a good agreement between the predicted and actual overall survival. The radiomics-clinical nomogram and radiomics score might be non-invasive and reliable methods for the risk stratification in patients with hypopharyngeal squamous cell carcinoma. • An MRI-based radiomics model was constructed to evaluate of OS in patients with hypopharyngeal squamous cell carcinoma. • A radiomics-clinical nomogram that combined radiomics features and clinical characteristics was established. • Multi-cohort study validated the predictive performance of the radiomics-clinical nomogram to stratify patients with high risk in clinical practice.

We have read the remarkable report by Rich N et al. and would like to propose that the tumor growth model of hepatocellular carcinoma (HCC) should be based on a distributed algorithm that includes damping factors and not on a simple exponential function. We would like to share some of our views on growth model of Hepatocellular carcinoma (HCC) that may differ from the valuable report by Rich N and colleagues.

Objective The purpose of the present study was to investigate Mandarin tone production performance of prelingually deafened children with cochlear implants (CIs) using modified acoustic analyses and to evaluate the relationship between demographic factors of those CI children and their tone production ability. Methods Two hundred seventy-eight prelingually deafened children with CIs and 173 age-matched normal-hearing (NH) children participated in the study. Thirty-six monosyllabic Mandarin Chinese words were recorded from each subject. The fundamental frequencies (F0) were extracted from the tone tokens. Two acoustic measures (i.e., differentiability and hit rate) were computed based on the F0 onset and offset values (i.e., the tone ellipses of the two-dimensional [2D] method) or the F0 onset, midpoint, and offset values (i.e., the tone ellipsoids of the 3D method). The correlations between the acoustic measures as well as between the methods were performed. The relationship between demographic factors and acoustic measures were also explored. Results The children with CIs showed significantly poorer performance in tone differentiability and hit rate than the NH children. For both CI and NH groups, performance on the two acoustic measures was highly correlated with each other (r values: 0.895-0.961). The performance between the two methods (i.e., 2D and 3D methods) was also highly correlated (r values: 0.774-0.914). Age at implantation and duration of CI use showed a weak correlation with the scores of acoustic measures under both methods. These two factors jointly accounted for 15.4-18.9% of the total variance of tone production performance. Conclusion There were significant deficits in tone production ability in most prelingually deafened children with CIs, even after prolonged use of the devices. The strong correlation between the two methods suggested that the simpler, 2D method seemed to be efficient in acoustic assessment for lexical tones in hearing-impaired children. Age at implantation and especially the duration of CI use were significant, although weak, predictors for tone development in pediatric CI users. Although a large part of tone production ability could not be attributed to these two factors, the results still encourage early implantation and continual CI use for better lexical tone development in Mandarin-speaking pediatric CI users.

To explore and analyze the epidemic features of coronavirus disease 2019 (COVID-19) in Hunan Province from January 21, 2020 to March 14, 2020, as well as to investigate the COVID-19 epidemics in each city of Hunan Province.The epidemic data was obtained from the official website of Hunan Province's Health Commission. The data of each city of Hunan Province was analyzed separately. Spatial distribution of cumulative confirmed COVID-19 patients and the cumulative occurrence rate was drawn by ArcGIS software for each city in Hunan Province. Some regional indexes were also compared with that in the whole country.The first patient was diagnosed in January 21, sustained patient growth reached its plateau in around February 17. Up to March 14, the cumulative confirmed COVID-19 patients stopped at 1 018. The cumulative occurrence rate of COVID-19 patients was 0.48 per 0.1 million person. The number of cumulative severe patients was 150 and the number of cumulative dead patients was 4. The mortality rate (0.39%) and the cure rate (99.6%) in Hunan Province was significantly lower and higher respectively than the corresponding average rate in the whole country (0.90% and 96.2%, Hubei excluded). The first 3 cities in numbers of the confirmed patients were Changsha, Yueyang, and Shaoyang. While sorted by the cumulative occurrence rate, the first 3 cities in incidence were Changsha, Yueyang, and Zhuzhou.The epidemic of COVID-19 spread out smoothly in Hunan Province. The cities in Hunan Province implement anti-disease strategies based on specific situations on their own and keep the epidemic in the range of controllable.

The prognosis of colorectal cancer (CRC) is largely dependent on the early detection of hepatic metastases. With the advantages of nonradioactivity and the availability of multiple scanning sequences, the efficacy of magnetic resonance imaging (MRI) in the detection of colorectal liver metastases (CRLM) is not yet clear. We performed this meta-analysis to address this issue. PubMed, Embase, and the Cochrane Library were searched for studies reporting diagnostic performance of MRI for CRLM. Descriptive and quantitative data were extracted. The study quality was evaluated for the identified studies and a random effects model was used to determine the integrated diagnosis estimation. Meta-regression and subgroup analyses were implemented to investigate the potential contributors to heterogeneity. As a result, seventeen studies were included for analysis (from the year 1996 to 2018), comprising 1121 patients with a total of 3279 liver lesions. The pooled sensitivity, specificity, and diagnostic odds ratio were 0.90 (95% confidence intervals (CI): 0.81–0.95), 0.88 (0.80–0.92), and 62.19 (23.71–163.13), respectively. The overall weighted area under the curve was 0.94 (0.92–0.96). Using two or more imaging planes and a quantitative/semiquantitative interpretation method showed higher diagnostic performance, although only the latter demonstrated statistical significance (P

Background miR-20a is a critical molecule in various biological processes and cancer progression procedures. However, its relationships with lncRNAs and their functional pathway analysis in breast tumorigenesis are less intensively studied. Methods The expression data from TCGA database and multiple bioinformatics resources were used to check the expression levels, survival curves, interactions and functional illustrations of miR-20a and its related lncRNAs (XIST, H19 and MALAT1) in breast cancer patients. The luciferase reporter assays and Pearson's correlation analyses were utilized to verify the direct regulatory relationship between miR-20a and three lncRNAs (XIST, H19 and MALAT1). In vitro cell proliferation, migration and invasion assays, were performed to check the biological effects of miR-20a and XIST in different breast cancer cell lines. The receiver operating characteristic curve (ROC) analyses were done for evaluating diagnostic values of serum miR-20a and XIST in breast cancer patients. Results The miR-20a expression was significantly up-regulated in both breast cancer samples and serum samples, and correlated with poor survival rate in breast cancer patients. LncRNAs (XIST, H19 and MALAT1) directly bound to hsa-miR-20a and were negatively correlated with hsa-miR-20a expression in breast cancer patient samples. For functional illustrations and downstream signaling pathways analysis, XIST, H19 and MALAT1 mainly shared their regulatory functions in cell motility and interleukin signaling in breast cancer progression. Additionally, over-expression of miR-20a and inhibition of XIST promoted breast cancer cell growth, migration and invasion in vitro, and serum miR-20a and XIST served as potential diagnostic biomarkers for breast cancer with the area under ROC curve (AUC) of 0.87 (95% CI = 0.78 to 0.97), and 0.78 (95% CI = 0.67 to 0.89) respectively. Conclusions Taken together, these findings provide us novel insights and avenues for utilizing miR-20a and its related lncRNAs as potential diagnostic biomarkers and promising therapeutic targets for breast cancer treatment.

Many patients with sensorineural hearing loss have a precipitous high-frequency loss with relatively good thresholds in the low frequencies. This present paper briefly introduces and compares the basic principles of four types of frequency lowering algorithms with emphasis on nonlinear frequency compression (NLFC). A review of the effects of the NLFC algorithm on speech and music perception and sound quality appraisal is then provided. For vowel perception, it seems that the benefits provided by NLFC are limited, which are probably related to the parameter settings of the compression. For consonant perception, several studies have shown that NLFC provides improved perception of high-frequency consonants such as /s/ and /z/. However, a few other studies have demonstrated negative results in consonant perception. In terms of sentence recognition, persistent use of NLFC might provide improved performance. Compared to the conventional processing, NLFC does not alter the speech sound quality appraisal and music perception as long as the compression setting is not too aggressive. In the subsequent section, the relevant factors with regard to NLFC settings, time-course of acclimatization, listener characteristics, and perceptual tasks are discussed. Although the literature shows mixed results on the perceptual efficacy of NLFC, this technique improved certain aspects of speech understanding in certain hearing-impaired listeners. Little research is available on speech perception outcomes in languages other than English. More clinical data are needed to verify the perceptual efficacy of NLFC in patients with precipitous high-frequency hearing loss. Such knowledge will help guide clinical rehabilitation of those patients. Keywords: Nonlinear frequency compression, Hearing loss, Hearing aids, Speech perception, Music perception

// Luqing Zhao 1, 4 , Yuelong Zhao 3 , Yanong He 3 and Yitao Mao 2 1 Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China 2 Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China 3 School of Computer Science and Engineering, South China University of Technology, Guangzhou, Guangdong 510640, China 4 Department of Pathology, School of Basic Medical Science, Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China Correspondence to: Yitao Mao, email: yitaomcsu@163.com Keywords: miR-19b, MYLIP, cell adhesion molecules, breast cancer, metastasis Received: February 03, 2017 Accepted: June 19, 2017 Published: July 17, 2017 ABSTRACT miR-19b is a key molecule for cancer development, however its crucial roles in breast cancer metastasis are rarely studied right now. In this study, using several bioinformatics databases to predict the downstream targets for miR-19b, we verified that a novel target gene, myosin regulatory light chain interacting protein (MYLIP), could be directly down-regulated by miR-19b through its 3'-UTR region. MYLIP belongs to the cytoskeletal protein clusters and is involved in the regulation of cell movement and migration. We further explored that miR-19b was highly expressed and negatively correlated with MYLIP expression in breast cancer patient samples from the TCGA database. And the over-expression of miR-19b or inhibition of MYLIP facilitated the migration and metastasis of breast cancer cells, through conducting the wound healing assay and transwell invasion assay. Additionally, miR-19b could obviously promote breast tumor growth in mouse models and affect the expressions of cell adhesion molecules (including E-Cadherin, ICAM-1 and Integrin β1) by down-regulating E-Cadherin expression and up-regulating ICAM-1 and Integrin β1 expressions in vitro and in vivo . Meanwhile, miR-19b effectively activated the Integrin β downstream signaling pathways (such as the Ras-MAPK pathway and the PI3K-AKT pathway) and elevated the expression levels of essential genes in these two pathways. Taken together, these findings comprehensively illustrate the regulatory mechanisms ofmiR-19b in breast cancer metastasis, and provide us new insights for exploring MYLIP and its related cell adhesion molecules as promising therapeutic targets to interfere breast cancer development.

To explore the feasibility and efficacy of artificial neural network for differentiating high-grade glioma and low-grade glioma using image information. Methods: A total of 130 glioma patients with confirmed pathological diagnosis were selected retrospectively from 2012 to 2017. Forty one imaging features were extracted from each subjects based on 2-dimension magnetic resonance T1 weighted imaging with contrast-enhancement. An artificial neural network model was created and optimized according to the performance of feature selection. The training dataset was randomly selected half of the whole dataset, and the other half dataset was used to verify the performance of the neural network for glioma grading. The training-verification process was repeated for 100 times and the performance was averaged. Results: A total of 5 imaging features were selected as the ultimate input features for the neural network. The mean accuracy of the neural network for glioma grading was 90.32%, with a mean sensitivity at 87.86% and a mean specificity at 92.49%. The area under the curve of receiver operating characteristic curve was 0.9486. Conclusion: As a technique of artificial intelligence, neural network can reach a relatively high accuracy for the grading of glioma and provide a non-invasive and promising computer-aided diagnostic process for the pre-operative grading of glioma.目的：探讨利用人工神经网络对脑胶质瘤进行分级的可行性和有效性。方法：回顾性纳入2012至2017年经病理证实的130例脑胶质瘤患者，基于磁共振增强T1加权相二维图像提取的共41个影像学特征。建立人工神经网络并进行特征选择以得到最优化的神经网络模型，随机抽取一半病例的影像学特征数据对神经网络进行训练，并用另一半特征数据对训练完成后的神经网络进行胶质瘤分级效果验证。对神经网络重复进行100次训练和验证，将结果进行平均。结果：经过特征选择后的神经网络模型共选取5个特征作为输入特征，神经网络对脑胶质瘤分级的平均准确率为90.32%，平均敏感度为87.86%，平均特异度为92.49%，受试者操作曲线的曲线下面积为0.9486。结论：人工神经网络作为一种人工智能方法，对脑胶质瘤分级具有较高的准确性，为脑胶质瘤的无创性术前分级提供了可行的辅助手段。.

// Luqing Zhao 1,2,3,4 , Yitao Mao 5 , Yuelong Zhao 7 , Ya Cao 6 and Xiang Chen 1,2 1 Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China 2 Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China 3 Department of Pathology, School of Basic Medical Science, Xiangya School of Medicine, Central South University, Changsha, Hunan, China 4 Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China 5 Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, China 6 Cancer Research Institute, School of Basic Medical Science, Xiangya School of Medicine, Central South University, Changsha, Hunan, China 7 School of Information Sceince and Engineering, Central South University, Changsha, Hunan, China Correspondence to: Xiang Chen, email: // Luqing Zhao, email: // Keywords : glucose metabolism, multifaceted regulators, p53, HIF-1, TIGAR Received : October 14, 2015 Accepted : February 16, 2016 Published : February 26, 2016 Abstract Aberrant glucose metabolism, “aerobic glycolysis” or “Warburg effect”, is a hallmark of human cancers. There is a cluster of “ multifaceted regulators ”, which plays a pivotal role in the regulation of glucose metabolism. They can not only modulate the activities of specific enzymes, but also act as transcriptional activators to regulate the expression of metabolism related genes. Additionally, they can crosstalk with other key factors involved in glucose metabolism and work together to initiate multiple oncogenic processes. These “ multifaceted regulators ”, especially p53, HIF-1, TIGAR and microRNA, will be focused in this review. And we will comprehensively illustrate their regulatory effects on cancer glucose metabolism, and further elaborate on their clinical significance. In-depth elucidation the role of “ multifaceted regulators ” in cancer glucose metabolism will provide us novel insights in cancer research field and offer promising therapeutic targets for anti-cancer therapies.

Objectives/Hypothesis The present study aimed to examine whether the response patterns to the chimeric lexical tone tokens, combined with their pure tone audiometry (PTA) results, could separate listeners with sensorineural hearing loss (SNHL) from listeners with auditory neuropathy spectrum disorder (ANSD). Study Design Case-control study. Methods Forty-three SNHL subjects and 46 ANSD subjects participated in a Mandarin lexical tone perception test using original and chimeric tone tokens. Ten sets of monosyllables, with four tone patterns for each, were processed through a 16-channel chimeric synthesizer in which a temporal envelope (E) from a monosyllabic word of one tone was paired with a fine structure (FS) from the same monosyllable of other tones. Results Significantly negative correlations were present between tone perception scores and PTA0.5–4 kHz for both SNHL (P < 0.001) and ANSD (P < 0.001) subjects. Overall, 72.4%, 66.4%, and 46.3% of the tone responses were consistent with FS for the SNHL subjects with mild, moderate, and severe degree of hearing loss, respectively; and 28.4%, 23.1%, and 22.7% were consistent with FS for the ANSD subjects, with the equivalent degree of hearing loss. Similarly, 17.6%, 24.2%, and 37.7% of the tone responses were consistent with E for the SNHL subjects with mild, moderate, and severe degree of hearing loss, respectively; and 45.5%, 44.3%, and 36.5% were consistent with E for the ANSD subjects. Conclusion Subjects with SNHL and ANSD may be separated by representing their FS- and E-consistent tone responses as a function of their pure-tone hearing thresholds. Level of Evidence 3b. Laryngoscope, 2015

Previous studies have shown that lexical tone perception in quiet relies on the acoustic temporal fine structure (TFS) but not on the envelope (E) cues. The contributions of TFS to speech recognition in noise are under debate. In the present study, Mandarin tone tokens were mixed with speech-shaped noise (SSN) or two-talker babble (TTB) at five signal-to-noise ratios (SNRs; −18 to +6 dB). The TFS and E were then extracted from each of the 30 bands using Hilbert transform. Twenty-five combinations of TFS and E from the sound mixtures of the same tone tokens at various SNRs were created. Twenty normal-hearing, native-Mandarin-speaking listeners participated in the tone-recognition test. Results showed that tone-recognition performance improved as the SNRs in either TFS or E increased. The masking effects on tone perception for the TTB were weaker than those for the SSN. For both types of masker, the perceptual weights of TFS and E in tone perception in noise was nearly equivalent, with E playing a slightly greater role than TFS. Thus, the relative contributions of TFS and E cues to lexical tone perception in noise or in competing-talker maskers differ from those in quiet and those to speech perception of non-tonal languages.

A B S T R A C T S Objective: The purpose of the present study was to investigate vocal singing performance of hearingimpaired children with cochlear implants (CI) and hearing aids (HA) as well as to evaluate the relationship between demographic factors of those hearing-impaired children and their singing ability. Methods: Thirty-seven prelingually-deafened children with CIs and 31 prelingually-deafened children with HAs, and 37 normal-hearing (NH) children participated in the study. The fundamental frequencies (F0) of each note in the recorded songs were extracted and the duration of each sung note was measured. Five metrics were used to evaluate the pitch-related and rhythm-based aspects of singing accuracy. Results: Children with CIs and HAs showed significantly poorer performance in either the pitch-based assessments or the rhythm-based measure than the NH children. No significant differences were seen between the CI and HA groups in all of these measures except for the mean deviation of the pitch intervals. For both hearing-impaired groups, length of device use was significantly correlated with singing accuracy. Conclusions: There is a marked deficit in vocal singing ability either in pitch or rhythm accuracy in a majority of prelingually-deafened children who have received CIs or fitted with HAs. Although an increased length of device use might facilitate singing performance to some extent, the chance for the hearing-impaired children fitted with either HAs or CIs to reach high proficiency in singing is quite slim.

DDX3X, located on the X-chromosome, belongs to the DEAD-box RNA helicase family and acts as a key RNA-binding protein to exert its regulatory functions in various biological processes. In this paper, knock-down the expression of DDX3X can affect a subset of miRNA expression levels, especially for miR-1, miR-141, miR-145, miR-19b, miR-20a and miR-34a. Through adopting the immunoprecipitation (IP), RNA immunoprecipitation (RIP), dual luciferase reporter assays, we illustrate that DDX3X could interact with Drosha/DGCR8 complex, elevate the processing activity of Drosha/DGCR8 complex on pri-miRNAs, and increase mature miRNA expression levels. For the studies of potential roles and biological functions of DDX3X-dependent miRNAs and their downstream target genes in multiple cancers, we use the primary data from The Cancer Genome Atlas (TCGA), Ingenuity Pathway Analysis (IPA) and several miRNA target prediction databases, to systematically analyze the expression levels of DDX3X-dependent miRNAs in almost 14 kinds of cancers versus normal tissues, and the essential biological functions for their putative downstream target genes. All these findings will provide us novel insights and directions for thoroughly exploring the regulatory mechanisms of miRNA biogenesis, and shed light on effectively searching the clinical significances and biological roles of DDX3X-dependent miRNAs and their target genes in cancer development.

The purpose of the present study was to investigate Mandarin tone recognition in background noise in children with cochlear implants (CIs), and to examine the potential factors contributing to their performance.Tone recognition was tested using a two-alternative forced-choice paradigm in various signal-to-noise ratio (SNR) conditions (i.e. quiet, +12, +6, 0, and -6 dB). Linear correlation analysis was performed to examine possible relationships between the tone-recognition performance of the CI children and the demographic factors.Sixty-six prelingually deafened children with CIs and 52 normal-hearing (NH) children as controls participated in the study.Children with CIs showed an overall poorer tone-recognition performance and were more susceptible to noise than their NH peers. Tone confusions between Mandarin tone 2 and tone 3 were most prominent in both CI and NH children except for in the poorest SNR conditions. Age at implantation was significantly correlated with tone-recognition performance of the CI children in noise.There is a marked deficit in tone recognition in prelingually deafened children with CIs, particularly in noise listening conditions. While factors that contribute to the large individual differences are still elusive, early implantation could be beneficial to tone development in pediatric CI users.

Since the concept of the secretome (ensemble of proteins secreted and/or shed from cells) was proposed, it has become an attractive and challenging proteomic technology in recent years. However, secretome analysis still faces some difficulties mainly related to sample collection and preparation. In the present study, we established a reliable method for extracting secreted proteins by ultrafiltration centrifugation and conducting secretomic analysis. Accumulating evidence suggests that carcinoma-associated stromal fibroblasts (CAFs) play an important role in cancer initiation and progression. To investigate the expression patterns of secreted proteins from fibroblasts and to identify the secreted proteins involved in nasopharyngeal carcinoma (NPC) carcinogenesis, we conducted comparative secretome analysis between CAFs and normal fibroblasts. After two-dimensional gel electrophoresis (2-D PAGE), 11 significant spots were differentially expressed and identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). These proteins may take part in the regulation of the tumor micro-environment through different processes. The expression level of galectin-1 in the CAF supernatant was also determined by ELISA. This study provides useful information and new clues for the further understanding of the regulatory mechanisms of CAFs in the NPC microenvironment.

The present study aimed to examine whether the response patterns to the chimeric lexical tone tokens, combined with their pure tone audiometry (PTA) results, could separate listeners with sensorineural hearing loss (SNHL) from listeners with auditory neuropathy spectrum disorder (ANSD).Case-control study.Forty-three SNHL subjects and 46 ANSD subjects participated in a Mandarin lexical tone perception test using original and chimeric tone tokens. Ten sets of monosyllables, with four tone patterns for each, were processed through a 16-channel chimeric synthesizer in which a temporal envelope (E) from a monosyllabic word of one tone was paired with a fine structure (FS) from the same monosyllable of other tones.Significantly negative correlations were present between tone perception scores and PTA0.5-4 kHz for both SNHL (P0.001) and ANSD (P0.001) subjects. Overall, 72.4%, 66.4%, and 46.3% of the tone responses were consistent with FS for the SNHL subjects with mild, moderate, and severe degree of hearing loss, respectively; and 28.4%, 23.1%, and 22.7% were consistent with FS for the ANSD subjects, with the equivalent degree of hearing loss. Similarly, 17.6%, 24.2%, and 37.7% of the tone responses were consistent with E for the SNHL subjects with mild, moderate, and severe degree of hearing loss, respectively; and 45.5%, 44.3%, and 36.5% were consistent with E for the ANSD subjects.Subjects with SNHL and ANSD may be separated by representing their FS- and E-consistent tone responses as a function of their pure-tone hearing thresholds.3b. Laryngoscope, 126:1420-1425, 2016.

To explore and analyze the clinical characteristics and treatment strategy of severe complications caused by esophageal foreign bodies.A retrospective study was carried out on 49 cases with foreign bodies in esophagus through careful analysis of their clinical data to explore the associated problems with etiology and therapy. Among this complications, there were cases of 13 periesophageal abscess, 20 cases of abscess in the neck, 11 cases of mediastinal abscess, 3 tracheoesophageal fistula, 1 case of aorta injury and 1 septicemia.Forty-eight (97.96%) of the patients recovered while one died.Hard esophagoscopy under general anesthesia is the main therapeutic strategy to take out the esophageal foreign bodies. When it failed or severe complications such as perforation or others emerged, open surgery like lateral neck incision or thoracotomy supplemented with positive and timely supporting therapy are vital and essential.