Fine-tuning coreference resolution for different styles of clinical narratives.

OBJECTIVE: Coreference resolution (CR) is a natural language processing (NLP) task that is concerned with finding all expressions within a single document that refer to the same entity. This makes it crucial in supporting downstream NLP tasks such as summarization, question answering and information extraction. Despite great progress in CR, our experiments have highlighted a substandard performance of the existing open-source CR tools in the clinical domain. We set out to explore some practical solutions to fine-tune their performance on clinical data. METHODS: We first explored the possibility of automatically producing silver standards following the success of such an approach in other clinical NLP tasks. We designed an ensemble approach that leverages multiple models to automatically annotate co-referring mentions. Subsequently, we looked into other ways of incorporating human feedback to improve the performance of an existing neural network approach. We proposed a semi-automatic annotation process to facilitate the manual annotation process. We also compared the effectiveness of active learning relative to random sampling in an effort to further reduce the cost of manual annotation. RESULTS: Our experiments demonstrated that the silver standard approach was ineffective in fine-tuning the CR models. Our results indicated that active learning should also be applied with caution. The semi-automatic annotation approach combined with continued training was found to be well suited for the rapid transfer of CR models under low-resource conditions. The ensemble approach demonstrated a potential to further improve accuracy by leveraging multiple fine-tuned models. CONCLUSION: Overall, we have effectively transferred a general CR model to a clinical domain. Our findings based on extensive experimentation have been summarized into practical suggestions for rapid transferring of CR models across different styles of clinical narratives.

Association Between LIN28A Gene Polymorphisms and Glioma Susceptibility in Chinese Children.

Gliomas are the most prevalent brain tumors among children and adolescents. The occurrence and development of various malignant tumors is closely related with LIN28A gene, but its relationship with glioma susceptibility has not been widely discovered. In this case-control study, we conducted four single nucleotide polymorphisms (SNPs) (rs3811464 G>A, rs3811463 T>C, rs34787247 G>A, and rs11247957 G>A) of LIN28A gene to investigate whether they increase the risk of glioma. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate their relationship. There was no significant correlation between four SNPs and glioma risk in single polymorphism and conjoint analysis. However, in stratification analysis, we found that rs3811463 TC/CC may add to the risk of glioma with clinical stage III (adjusted OR = 3.16, 95% CI = 1.15-8.70, P = .026) or stage III+IV patients (adjusted OR = 2.05, 95% CI = 1.02-4.13, P = .044). Our research suggested that four SNPs of LIN28A gene have a weak relationship with the risk of glioma in Chinese children. LIN28A rs3811463 TC/CC may increase the possibility of glioma in clinical stage III or stage III+IV patients which need larger samples and further confirmation.

Long non-coding RNA GAS5, by up-regulating PRC2 and targeting the promoter methylation of miR-424, suppresses multiple malignant phenotypes of glioma.

PURPOSE: Malignant gliomas remain significant challenges in clinic and pose dismal prognosis on patients. In this study, we focused on growth arrest-specific 5 (GAS5), a tumor suppressive long non-coding RNA in glioma, explored its crosstalk with miR-424, and examined their biological functions in glioma. METHODS: Expressions of GAS5 and miR-424 were measured using qRT-PCR. The regulation of GAS5 on miR-424 expression was examined in GAS5-overexpressing glioma cells by combining methylation-specific PCR, western blotting, and RNA immunoprecipitation. Functional significance of GAS5 and miR-424 on in vitro cell proliferation, apoptosis, migration, invasion, and in vivo tumor growth was examined using colony formation, flow cytometry, wound healing, transwell assay, and the xenograft model, respectively. The potential targeting of AKT3 by miR-424 was investigated using luciferase reporter assay. RESULTS: GAS5 and miR-424 were significantly down-regulated in glioma cells. GAS5 directly interacted with enhancer of zeste homolog 2 (EZH2), stimulated the formation of polycomb repressive complex 2 (PRC2), reduced the levels of DNA methyltransferases (Dnmts), alleviated promoter methylation of miR-424, and promoted miR-424 expression. Functionally, GAS5, by up-regulating miR-424, inhibited cell proliferation, migration, and invasion, while increased apoptosis of glioma cells in vitro, and suppressed xenograft growth in vivo. miR-424 directly inhibited AKT3 and altered the expressions of AKT3 targets, cyclinD1, c-Myc, Bax, and Bcl-2, which might contribute to its tumor suppressive activities. CONCLUSIONS: GAS5, by inhibiting methylation and boosting expression of miR-424, inhibits AKT3 signaling and suppresses multiple malignant phenotypes. Therefore, stimulating GAS5/miR-424 signaling may benefit the treatment of glioma.

Identification of SEC61G as a Novel Prognostic Marker for Predicting Survival and Response to Therapies in Patients with Glioblastoma.

BACKGROUND The survival and therapeutic outcome vary greatly among glioblastoma (GBM) patients. Treatment resistance, including resistance to temozolomide (TMZ) and radiotherapy, is a great obstacle for these therapies. In this study, we aimed to evaluate the predictive value of SEC61G on survival and therapeutic response in GBM patients. MATERIAL AND METHODS Survival analyses were performed to assess the correlation between SEC61G expression and survival of GBM patients from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) datasets. Univariate and multivariate Cox proportional hazard regression analysis was introduced to determine prognostic factors with independent impact power. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were conducted to illustrate possible biological functions of SEC61G. RESULTS High expression of SEC61G was significantly correlated with poor prognosis in all GBM patients. High expression of SEC61G was also associated with poor outcome in those who received TMZ treatment or radiotherapy in TCGA GBM cohort. Univariate and multivariate Cox proportional hazards regression demonstrated that SEC61G was an independent prognostic factor affecting the prognosis and therapeutic outcome. The combination of age, SEC61G expression, and MGMT promoter methylation in survival analysis could provide better outcome assessment. Finally, a strong correlation between SEC61G expression and Notch pathway was observed in GSEA and GSVA, which suggested a possible mechanism that SEC61G affected survival and TMZ resistance. CONCLUSIONS SEC61G expression may be a potential prognostic marker of poor survival, and a predictor of poor outcome to TMZ treatment and radiotherapy in GBM patients.

Effects of Fibronectin 1 on Cell Proliferation, Senescence and Apoptosis of Human Glioma Cells Through the PI3K/AKT Signaling Pathway.

BACKGROUND/AIMS: The current study aimed to investigate the role by which fibronectin 1 (FN1) influences the cell cycle, senescence and apoptosis in human glioma cells through the PI3K/ AKT signaling pathway. METHODS: Differentially expressed genes (DEGs) were identified based on gene expression data (GSE12657, GSE15824 and GSE45921 datasets) and probe annotation files from Gene Expression Omnibus. The DEGs were identified in connection with gene ontology (GO) enrichment analysis and with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The positive expression of the FN1 protein was detected by immunohistochemistry. The glioma cell lines U251 and T98G were selected and assigned into blank, negative control (NC) and siRNA-FN1 groups. A dual luciferase reporter gene assay was used to investigate the effects of FN1 on transcriptional activity through the PI3K/AKT signaling pathway. An MTT assay was applied for the detection of cell proliferation, while flow cytometry was employed for cell cycle stage and cellular apoptosis detection. ß-galactosidase staining was utilized to detect cellular senescence, a scratch test was applied to evaluate cell migration, and a transwell assay was used to analyze cell invasion. Western blotting and qRT-PCR methods were used to detect the protein and mRNA expression levels, respectively, of the FN1 gene and the related genes in the PI3K/AKT pathway (PI3K, AKT and PTEN), the cell cycle (pRb, CDK4 and Cyclin D1) and cell senescence (p16 and p21) among the collected tissues and cells. RESULTS: GSE12657 profiling revealed FN1 to be the most upregulated gene in glioma. Regarding the GSE12657 and GSE15824 datasets, FN1 gene expression was higher in glioma tissues than in normal tissues. GO enrichment analysis and KEGG pathway enrichment analysis indicated that FN1 is involved in the synthesis of extracellular matrix (ECM) components and the PI3K/AKT signaling pathway. Verification was provided, indicating the role played by the FN1 gene in the regulation of the PI3K/AKT signaling pathway, as silencing the FN1 gene was found to inhibit cell proliferation, promote cell apoptosis and senescence, and reduce migration and invasion through the down-regulation of FN1 gene expression and disruption of the PI3K-AKT signaling pathway. CONCLUSION: The findings of this study provide evidence highlighting the prominent role played by FN1 in stimulating glioma growth, invasion, and survival through the activation of the PI3K/AKT signaling pathway.

Cross-domain zero-shot learning for enhanced fault diagnosis in high-voltage circuit breakers.

Ensuring the stability of high-voltage circuit breakers (HVCBs) is crucial for maintaining an uninterrupted supply of electricity. Existing fault diagnosis methods typically rely on extensive labeled datasets, which are challenging to obtain due to the unique operational contexts and complex mechanical structures of HVCBs. Additionally, these methods often cater to specific HVCB models and lack generalizability across different types, limiting their practical applicability. To address these challenges, we propose a novel cross-domain zero-shot learning (CDZSL) approach specifically designed for HVCB fault diagnosis. This approach incorporates an adaptive weighted fusion strategy that combines vibration and current signals. To bypass the constraints of manual fault semantics, we develop an automatic semantic construction method. Furthermore, a multi-channel residual convolutional neural network is engineered to distill deep, low-level features, ensuring robust cross-domain diagnostic capabilities. Our model is further enhanced with a local subspace embedding technique that effectively aligns semantic features within the embedding space. Comprehensive experimental evaluations demonstrate the superior performance of our CDZSL approach in diagnosing faults across various HVCB types.

Beyond seen faults: Zero-shot diagnosis of power circuit breakers using symptom description transfer.

Power circuit breakers (CBs) are vital for the control and protection of power systems, yet diagnosing their faults accurately remains a challenge due to the diversity of fault types and the complexity of their structures. Traditional data-driven methods, although effective, require extensive labeled data for each fault class, limiting their applicability in real-world scenarios where many faults are unseen. This paper addresses these limitations by introducing symptom description transfer-based zero-shot fault diagnosis (SDT-ZSFD), a method that leverages zero-shot learning for fault diagnosis. Our approach constructs a fault symptom description (FSD) framework, which embeds a fault symptom layer between the feature layer and the label layer to facilitate knowledge transfer from seen to unseen fault classes. The method utilizes current and acceleration signals collected during CB operation to extract features. By applying sparse principal component analysis to these signals, we derive high-quality features that are mapped to the FSD framework, enabling effective zero-shot learning. Our method achieves a satisfactory recognition rate by accurately diagnosing unseen faults based on these symptoms. This approach not only overcomes the data scarcity problem but also holds potential for practical applications in power system maintenance. The SDT-ZSFD method offers a reliable solution for CB fault diagnosis and provides a foundation for future improvements in symptom-based zero-shot diagnostic mechanisms and algorithmic robustness.

Effect of moxibustion on ATP-sensitive potassium channel (KATP) of bladder in detrusor overactivity rats. / 隔姜隔盐灸"神阙"å¯¹é€¼å°¿è‚Œè¿‡åº¦æ´»åŠ¨å¤§é¼ è†€èƒ±ATP敏感性钾离子通道的影响.

OBJECTIVES: To observe the effect of ginger-salt-partitioned moxibustion on ATP-sensitive potassium (KATP) channel of bladder in detrusor overactivity (DO) rats. METHODS: Female SD rats were randomly divided into sham operation, model, moxibustion and antagonist groups (n=9 in each group). Thorax (T) 10 spinal cord transection was performed by surgery. Ginger-salt partitioned moxibustion was applied to "Shenque" (CV8) for 3 cones, once daily for 14 consecutive days. Rats of the antagonist group were intraperitoneally injected with KATP channel specific antagonist glibenclamide (10 µg·kg-1·d-1) once daily for 14 consecutive days. Urodynamic tests were performed after treatment. The distribution and expression of KATP channel tetrameric subunit (SUR2B) in the bladder of rats was observed by immunofluorescence. The protein and mRNA expression levels of SUR2B in bladder tissue were detected by Western blot and qPCR respectively. RESULTS: Compared with the sham operation group, rats of the model group showed intensive and large phasic contractions of the detrusor during bladder filling, the frequency and amplitude of phasic contractions of the detrusor 5 min before leakage were significantly increased (P<0.001)；the voiding threshold pressure was significantly decreased (P<0.001)；the bladder perfusion volume was increased (P<0.001)；the SUR2B protein and mRNA expression in bladder tissue were significantly reduced (P<0.001). Compared with the model group and the antagonist group, the above-mentioned indicators in the moxibustion group were all reversed (P<0.01, P<0.001, P<0.05). CONCLUSIONS: Ginger-salt partitioned moxibustion can reduce the frequency and amplitude of detrusor phase contraction during bladder filling and prolong the time of first phase contraction in DO rats, which may be associated with up-regulating the expression level of KATP channel protein and mRNA, promoting the outflow of potassium ions, and inhibiting the inflow of calcium ions, thus improve the stability of detrusor during storage.

The role of m6A-modified CircEPHB4 in glioma pathogenesis: Insights into cancer stemness metastasis.

OBJECTIVE: While existing literature has provided insights into involvement of circEPHB4, SOX2 in glioma, their precise molecular mechanisms and synergistic implications in glioma pathogenesis still dim. This study aims to investigate significance and underlying mechanism of m6A-modified circEPHB4 in regulating SOX2/PHLDB2 axis in gliomas. METHODS: The mRNA and protein expression were tested by qRT-PCR and Western blot, respectively. ChIP assay was performed to detect SOX2 enrichment on the PHLDB2 promoter. Cell sphere-forming assay to detect self-renewal ability, flow cytometry to determine positivity of CD133 expressions, Malignant behavior of glioma cells were detected by CCK-8, plate colony formation, scratch, and transwell assays. Glioma xenograft models were constructed to investigate effects of CircEPHB4 in tumor development in vivo. RESULTS: Methyltransferase MELLT3 upregulated m6A modification of CircEPHB4, and YTHDC1 promoted cytoplasmic localization of m6A-modified CircEPHB4. Overexpression of wild-type CircEPHB4 enhanced glioma cells' stemness, metastasis, and proliferation. Cytoplasmic CircEPHB4 increased SOX2 mRNA stability by binding to IGF2BP2, and the effects observed by SOX2 knockdown were reversed by CircEPHB4 in glioma cells. SOX2 promoted transcriptional expression of PHLDB2 by enriching the PHLDB2 promoter region. SOX2 reversed the inhibition of PHLDB2 knockdown on stemness of glioma, cell proliferation, and metastasis. In vivo experiments also revealed that CircEPHB4 upregulated PHLDB2 expression by stabilizing SOX2 mRNA, which promoted in vivo tumor growth and accelerated stemness of glioma cells and metastasis. CONCLUSION: This study reveals functional interaction and molecular mechanisms of m6A-modified circEPHB4 in regulating SOX2/PHLDB2 axis, highlighting their importance in glioma pathogenesis and potential as therapeutic targets.

Transmission Electron Microscopy Peeled Surface Defect of Perovskite Quantum Dots to Improve Crystal Structure.

Transmission electron microscopy (TEM) is an excellent characterization method to analyze the size, morphology, crystalline state, and microstructure of perovskite quantum dots (PeQDs). Nevertheless, the electron beam of TEM as an illumination source provides high energy, which causes morphological variation (fusion and melting) and recession of the crystalline structure in low radiolysis tolerance specimens. Hence, a novel and facile strategy is proposed: electron beam peel [PbBr6]4- octahedron defects from the surface of QDs to optimize the crystal structure. TEM and high-angle annular dark-field scanning TEM (HAADF) tests indicate that the [PbBr6]4- octahedron would be peeled from the surface of QDs when QDs samples were irradiated under high-power irradiation, and then a clear image would be obtained. To avoid interference from a protective film of "carbon deposits" on the surface of the sample when using high resolution TEM, amorphous carbon film (15-20 nm) was deposited on the surface of QDs film and then characterized by TEM and HAADF. The detection consequences showed that the defection of PbBr2 on the surface of QDs will gradually disappear with the extension of radiation time, which further verifies the conjecture.

Association of RNA m7G Modification Gene Polymorphisms with Pediatric Glioma Risk.

Glioma stemming from glial cells of the central nervous system (CNS) is one of the leading causes of cancer death in childhood. The genetic predisposition of glioma is not fully understood. METTL1-WDR4 methyltransferase complex is implicated in tumorigenesis by catalyzing N7-methylguanosine (m7G) modification of RNA. This study is aimed at determining the association of glioma risk with three polymorphisms (rs2291617, rs10877013, and rs10877012) in METTL1 and five polymorphisms (rs2156315 rs2156316, rs6586250, rs15736, and rs2248490) in WDR4 gene in children of Chinese Han. We enrolled 314 cases and 380 controls from three independent hospitals. Genotypes of these polymorphisms were determined using the TaqMan assay. We found the WDR4 gene rs15736 was significantly associated with reduced glioma risk (GA/AA vs. GG: adjusted odds ratio = 0.63, 95%confidence interval = 0.42 - 0.94, P = 0.023) out of the eight studied polymorphisms. Stratified analyses showed that the association of rs15736 with the risk of glioma remained significant in children aged 60 months or older, girls, the subgroups with astrocytic tumors, or grade I + II glioma. We also found the combined effects of five WDR4 gene polymorphisms on glioma risk. Finally, expression quantitative trait locus (eQTL) analyses elucidated that the rs15736 polymorphism was related to the expression level of WDR4 and neighboring gene cystathionine-beta-synthase (CBS). Our finding provided evidence of a causal association between WDR4 gene polymorphisms and glioma susceptibility in Chinese Han children.

Mechanism of traditional Chinese medicine in treating overactive bladder.

Overactive bladder syndrome (OAB) has made increasing progress in mechanism and treatment research. Traditional Chinese medicine (TCM) is a common complementary therapy for OAB, and it has been found to be effective. However, the intervention mechanism of TCM in the treatment of OAB is still unclear. The aim of this review is to consolidate the current knowledge about the mechanism of TCM: acupuncture, moxibustion, herbs in treating OAB, and the animal models of OAB commonly used in TCM. Finally, we put forward the dilemma of TCM treatment of OAB and discussed the insufficiency and future direction of TCM treatment of OAB.

The curative effect of fire needling combined with filiform needling on tension-type headache and its effect on the tenderness of pericranial muscles. / ç«é’ˆè”åˆæ¯«é’ˆæ²»ç–—ç´§å¼ æ€§å¤´ç—›çš„ç–—æ•ˆåŠå¯¹é¢ å‘¨è‚Œè‚‰åŽ‹ç—›çš„å½±å“.

OBJECTIVES: To observe the curative effect of fire needling pricking pericranial tender points combined with filiform needling on tension-type headache (TTH) and its effect on pericranial muscle tenderness, and explore the correlation between changes of headache symptoms and pericranial muscle tenderness in TTH, to analyze the influence of pericranial muscle tenderness on TTH. METHODS: A total of 41 TTH patients in the treatment group and 38 TTH patients in the control group completed the study. The patients in the treatment group were treated with fire needling at pericranial tender points combined with filiform needling at Baihui (GV20), Sishencong (EX-HN1), Shenting (GV24), Touwei (ST8) and Fengchi (GB20). The patients in the control group were only treated with the same filiform needling as the treatment group. Patients in the two groups were treated twice a week for 8 weeks. Before and after treatment, the days of headache onset, the number and distribution of pericranial muscle tender points were recorded, the degree of headache was evaluated by visual analogue scale and the threshold of pericranial muscle tender points were measured. The correlations between the changes of the days and degree of headache onset and the changes of the number and threshold of pericranial muscle tender points were analyzed. The effective rates in the two groups were calculated. RESULTS: Compared with those before treatment, the days of headache onset and the degree of headache were decreased (P<0.05) in the two groups；the number of pericranial muscle tender points was decreased (P<0.05) and the tenderness threshold was increased (P<0.05) in the treatment group. After treatment, compared with the control group, the days of headache onset, the degree of headache, and the number of pericranial muscle tender points were decreased (P<0.05), and the tenderness threshold was increased (P<0.05) in the treatment group. The decrease of the days and degree of headache was positively correlated with the decrease of number and the increase of tenderness threshold of pericranial muscle tender points (P<0.05). The effective rate in the treatment group was 87.80% (36/41), which was higher than 57.89% (22/38) in the control group (P<0.05). The most common anatomic location of tender points in baseline was superior trapezius muscle, followed by sternocleidomastoid muscle, superior nuchal line, temporal muscle, masseter muscle, etc. CONCLUSIONS: The fire needling at the pericranial muscle tender points combined with filiform needling on TTH patients can significantly improve the clinical symptoms and reduce the pericranial muscle tenderness. The pericranial muscle tenderness is an important factor in the pathogenesis of TTH.

Exploring the Correlation of Abnormal CXCL9 Expression with Immune Infiltration in Glioma and Patient Prognosis Based on TCGA and GTEx Databases.

In this study, we intend to identify key immune-related genes (IRGs) in gliomas using the TCGA and GTEx databases. Following collection of the RNA-seq data of lower-grade glioma (LGG) and glioblastoma (GBM) patients from the TCGA and GTEx databases, the differentially expressed IRGs (DE-IRGs) were screened. The ESTIMATE algorithm was utilized to evaluate StromalScore and ImmuneScore of LGG and GBM samples and a multifactorial Cox risk model was constructed to identify the related risk genes. The core IRGs of LGG and GBM were screened through a PPI network, followed by exploration of their correlation with glioma prognosis. The relationship between IRGs and immune cells in LGG and GBM was detected. In vitro assays were performed to detect the effect of CXCL9 on glioma cell development. We screened 403 and 492 DE-IRGs in LGG and GBM. StromalScore and ImmuneScore were related to overall survival in LGG, but not in GBM. CXCL9 was identified as a core gene in LGG and GBM and shared association with the prognosis of gliomas. Furthermore, a correlation was found between CXCL9 and immune infiltration of LGG and GBM. Glioma cell proliferation and invasion could be inhibited by silencing of CXCL9. Overall, CXCL9 is correlated to the prognosis of glioma patients and may accelerate glioma development via immune regulation.

Genetic variants in XPD gene and glioma susceptibility in Chinese children: A multicenter case-control study.

Background: Glioma is one of the central nervous system (CNS) tumors in children, accounting for 80% of malignant brain tumors. Nucleotide excision repair (NER) is a vital pathway during DNA damage repair progression. Xeroderma pigmentosum group D (XPD) or excision repair cross-complementing group 2 (ERCC2) is a critical factor in the NER pathway, playing an indispensable role in the DNA repair process. Therefore, the genetic variants in XPD may be associated with carcinogenesis induced by defects in DNA repair. Methods: We are the first to conduct a multi-center case-control study to investigate the correlation between XPD gene polymorphisms and pediatric glioma risk. We chose three single nucleotide polymorphisms and genotyped them using the TaqMan assay. Results: Although there is no significant association of these genetic variations with glioma susceptibility, the stratified analysis revealed that in the subtype of astrocytic tumors, the rs13181 TG/GG genotype enhanced glioma risk than the TT genotype, and carriers with two to three genotypes also elevated the tumor risk than 0-1 genotypes. Conclusion: In conclusion, our findings provided an insight into the impact of XPD genetic variants on glioma risk.

Research Advances of Soil Corrosion of Grounding Grids.

A grounding grid plays the role of discharging current and balancing voltage to ensure the safety of the power system. However, soil corrosion can damage the grounding grid, which then can endanger the safe operation of power system. This paper reviewed recent research advances of soil corrosion of grounding grid. The cause, mechanism, types, and influencing factors of soil corrosion of grounding grids were summarized, and the corresponding detection technology and protective measures were also introduced. The paper pointed out that soil corrosion is a serious threat to the grounding grid system. Moreover, the impact mechanism of AC stray current, new corrosion detection technology, and better protective measures still need in-depth research.

No Association Between FTO Gene Polymorphisms and Central Nervous System Tumor Susceptibility in Chinese Children.

BACKGROUND: Central nervous system (CNS) tumor is a malignancy commonly seen occurring in childhood, worldwide. Fat mass and obesity-associated (FTO) enzyme, initially identified as an obesity-related protein, also functions as a susceptibility gene for cancers. However, predisposing effect of FTO gene single nucleotide polymorphisms (SNPs) on CNS tumor risk remains unknown. METHODS: Herein, we genotyped 314 CNS tumor patients and 380 healthy controls samples from three hospitals to explore whether FTO gene SNPs impact CNS tumor risk. TaqMan SNP genotyping assay was applied for the genotyping. Odds ratios (ORs) and 95% confidence intervals (CIs), generated from multinomial logistic regression, were applied to determine the associations of SNPs (rs1477196 G>A, rs9939609 T>A, rs7206790 C>G, and rs8047395 A>G) in FTO gene with risk of CNS tumor. RESULTS: We failed to detect significant associations between FTO gene SNPs and CNS tumor risk, either in single-locus or combined analysis. A significantly increased ependymoma risk was found for carriers with 3-4 risk genotypes in comparison to 0-2 risk genotypes (adjusted OR=1.94, 95% CI=1.11-3.37, P=0.020). CONCLUSION: Our data indicated that FTO gene SNPs are unlikely to have large effects on CNS tumor risk but may have weaker effects.

CircRNA EPHB4 modulates stem properties and proliferation of gliomas via sponging miR-637 and up-regulating SOX10.

Gliomas are the most common type of primary brain tumors. CircRNA ephrin type-B receptor 4 (circEPHB4) is a circular RNA derived from the receptor tyrosine kinase EPHB4. However, the clinical significance and the specific roles of circEPHB4 in gliomas and glioma cancer stem cells (CSC) have not been studied. Here, we found that circEPHB4 (hsa_circ_0081519) and SOX10 were up-regulated and microRNA (miR)-637 was down-regulated in glioma tissues and cell lines. Consistently, circEPHB4 was positively correlated with SOX10 but negatively correlated with miR-637. The altered expressions of these molecules were independently associated with overall survival of patients. CircEPHB4 up-regulated SOX10 and Nestin by directly sponging miR-637, thereby stimulating stemness, proliferation and glycolysis of glioma cells. Functionally, silencing circEPHB4 or increasing miR-637 levels in glioma cells was sufficient to inhibit xenograft growth in vivo. In conclusion, the circEPHB4/miR-637/SOX10/Nestin axis plays a central role in controlling stem properties, self-renewal and glycolysis of glioma cells and predicts the overall survival of glioma patients. Targeting this axis might provide a therapeutic strategy for malignant gliomas.