Potential value of expression of receptor accessory protein 4 for evaluating the prognosis of lower-grade glioma patients.

BACKGROUND: REEP4 is involved in the regulation of the biological process of mitosis. Lower grade glioma (LGG), as a malignant tumor, is accompanied by abnormalities in mitosis, but there have been no reports of REEP4 so far. METHODS: We collected transcriptome data, DNA methylation data and the clinical characteristics of thousands of patients with LGG. Various big data analysis methods and molecular biology experiments were employed to reveal the impact of REEP4 on the pathological process of LGG. RESULTS: It was found that the expression of REEP4 was significantly elevated and negatively regulated by its methylation site. Therefore, both the high expression of REEP4 and low methylation state of cg16311504 showed that the patients are correlated with lower patient survival rate. In addition, high REEP4 expression participates in the regulation of various cancer-related cellular signaling pathways, such as the cell cycle, MAPK signaling pathway, NOD-like receptor signaling pathway, etc. More importantly, the level of immune cell infiltration significantly increased in the high expression group of REEP4 in the LGG tumor microenvironment and REEP4 has a high positive correlation with PD-L1 and other immune checkpoints. CONCLUSIONS: In brief, this study is the first to introduce REEP4 in malignant tumors, which can be used as an independent risk factor that participates in the malignant process of LGG. More importantly, REEP4 has the potential to become a new star in the field of anti-tumor treatment.

ZNF480 influences the prognosis, pathogenesis, and immune microenvironment in patients with lower-grade glioma.

ZNF480 has not yet attracted attention in the study of malignant tumors. Therefore, this study attempts to explain the significance of ZNF480 in the pathological process of lower-grade gliomas (LGG) based on large-scale samples from public database sources and in vitro experiments. Reverse transcription quantitative real-time polymerase chain reaction and immunohistochemistry confirmed that ZNF480 was highly expressed at both the mRNA and protein levels in LGG. Prognostic correlation analysis confirmed that the high expression of ZNF480, as an independent pathogenic gene, significantly correlates with poor survival in patients. Furthermore, the expression level of ZNF480 was significantly inhibited in SHG-44 cells treated with ademetionine disulfate tosylate. Gene set enrichment analysis showed that ZNF480 exists in multiple tumor-related signaling pathways, including the Notch signaling pathway. Immunological correlation analysis showed that ZNF480 can promote the LGG microenvironment to a high immune state and significantly enhance the infiltration of various immune cells, such as M2 macrophages. Finally, Spearman analysis showed a positive correlation of ZNF480 with many immune checkpoints, such as PD-L1. Overall, this study reveals for the first time the adverse effects of ZNF480 on the prognosis of tumor patients, which expands our understanding of the molecular mechanisms behind the regulation of ZNF480. We believe that the high expression of ZNF480 in LGG may be valuable for molecular targeted therapy or combined immunotherapy.

Clinical Outcomes After Cranioplasty With Titanium Mesh, Polyetheretherketone, or Composite Bone Cement: A Retrospective Study.

Cranioplasty is a common neurosurgical procedure; however, the optimal material choice remains controversial. At the time of this writing, autologous bone, the preferred choice for primary cranioplasty, has a high incidence of complications such as infection and resorption, thus requiring frequent use of synthetic materials. Therefore, this study aimed to compare the clinical benefits of titanium mesh (Ti), polyetheretherketone (PEEK), and composite bone cement (CBC) in cranioplasty to provide a clear selection basis for clinicians and patients. This study retrospectively collected data from 207 patients who underwent cranioplasty with Ti (n=129), PEEK (n=54), and CBC (n=24) between January 2018 and December 2020 at Henan Provincial People's Hospital. Postoperative follow-up information after 6 months was used to compare the long-term effects of the 3 materials on the patients. There were no significant differences in the overall complication rate after cranioplasty among the 3 materials. However, subcutaneous effusion was more frequent with PEEK (24.07%) and CBC (20.83%) than with Ti (2.33%). Second, there were no significant differences in the increase in Glasgow Outcome Scale and Karnofsky Performance Status scores after cranioplasty among the 3 materials. Finally, we found that PEEK had the highest patient satisfaction and hospitalization cost, whereas the opposite was true for Ti. Although the surgical outcomes of the 3 implant materials were similar, an examination of clinical outcomes such as patient satisfaction showed significant differences, deepening people's perceptions of the 3 materials.

Exploring the relationship between abnormally high expression of NUP205 and the clinicopathological characteristics, immune microenvironment, and prognostic value of lower-grade glioma.

Nuclear pore complex (NPC) is a major transport pivot for nucleocytoplasmic molecule exchange. Nucleoporin 205 (NUP205)-a main component of NPC-plays a key regulatory role in tumor cell proliferation; however, few reports document its effect on the pathological progression of lower-grade glioma (LGG). Therefore, we conducted an integrated analysis using 906 samples from multiple public databases to explore the effects of NUP205 on the prognosis, clinicopathological characteristics, regulatory mechanism, and tumor immune microenvironment (TIME) formation in LGG. First, multiple methods consistently showed that the mRNA and protein expression levels of NUP205 were higher in LGG tumor tissue than in normal brain tissue. This increased expression was mainly noted in the higher WHO Grade, IDH-wild type, and 1p19q non-codeleted type. Second, various survival analysis methods showed that the highly expressed NUP205 was an independent risk indicator that led to reduced survival time of patients with LGG. Third, GSEA analysis showed that NUP205 regulated the pathological progress of LGG via the cell cycle, notch signaling pathway, and aminoacyl-tRNA biosynthesis. Ultimately, immune correlation analysis suggested that high NUP205 expression was positively correlated with the infiltration of multiple immune cells, particularly M2 macrophages, and was positively correlated with eight immune checkpoints, particularly PD-L1. Collectively, this study documented the pathogenicity of NUP205 in LGG for the first time, expanding our understanding of its molecular function. Furthermore, this study highlighted the potential value of NUP205 as a target of anti-LGG immunotherapy.

PSRC1 Regulated by DNA Methylation Is a Novel Target for LGG Immunotherapy.

Proline and serine-rich coiled-coil 1 (PSRC1) has been reported to function as an oncogene in several cancers by regulating mitosis, while there are few reports on the role of PSRC1 in lower-grade glioma (LGG). Thus, this study collected 22 samples and 1126 samples from our institution and several databases, respectively, to explore the function of PSRC1 in LGG. First, the analysis of clinical characteristics showed that PSRC1 was always highly expressed in more malignant clinical characteristics of LGG, such as higher WHO grade, recurrence type, and IDH wild type. Second, the prognosis analysis revealed that the high expression of PSRC1 was an independent risk factor contributing to the shorter overall survival of LGG patients. Third, the analysis of DNA methylation showed that the expression of PSRC1 was associated with its 8 DNA methylation sites, overall negatively regulated by its DNA methylation level in LGG. Fourth, the analysis of immune correlation revealed that the expression of PSRC1 was positively correlated with the infiltration of 6 immune cells and the expression of 4 well-known immune checkpoints in LGG, respectively. Finally, co-expression analysis and KEGG analysis showed the 10 genes most related to PSRC1 and the signaling pathways involved by PSRC1 in LGG, respectively, such as MAPK signaling pathway and focal adhesion. In conclusion, this study identified the pathogenic role of PSRC1 in the pathological progression of LGG, expanding the molecular understanding of PSRC1, and provided a biomarker and potential immunotherapeutic target for the treatment of LGG.

Prognostic Significance of mRNA Expression RBBP8 or Its Methylation in Gliomas.

Retinoblastoma-binding protein 8 (RBBP8) affects the prognosis of patients with malignancies through various mechanisms. However, its function in gliomas is unknown. Our study explored the effects of RBBP8 on the prognosis of glioma patients, as well as its regulatory role in the glioma immune microenvironment. We used various bioinformatics methods to analyze the transcriptional profiles and methylation data of RBBP8 in gliomas from multiple databases. Our results showed that the mRNA and protein expression of RBBP8 in gliomas was higher than that in normal tissues and positively correlated with malignant clinical features such as age and WHO grade. A Kaplan-Meier analysis showed that patients with high RBBP8 expression had a poor prognosis. Cox regression demonstrated that RBBP8 was an independent risk indicator and had good diagnostic value for the poor prognosis of glioma. Importantly, RBBP8 was positively correlated with many well-known immune checkpoints (e.g., CTLA4 and PDL-1). Finally, a gene set enrichment analysis revealed that RBBP8 was remarkably enriched in cancer-related pathways such as cell cycle, DNA replication and so on. In conclusion, this study is the first to elaborate on the value of RBBP8 in the pathological process of glioma for anti-tumor immunotherapy. In addition, the expression of RBBP8 and its methylation site, cg05513509, may provide potential targets for glioma therapy.

Brain-targeted CRISPR/Cas9 nanomedicine for effective glioblastoma therapy.

CRISPR/Cas9 gene-editing technology shows great potential for treating a variety of diseases, such as glioblastoma multiforme (GBM). However, CRISPR components suffer from inherent delivery challenges, such as poor in vivo stability of Cas9 protein and gRNA, low blood-brain barrier (BBB) permeability and non-specific tissue or cell targeting. These defects have limited the application of Cas9/gRNA ribonucleoprotein (RNP) complexes for GBM therapy. Here, we developed a brain-targeted CRISPR/Cas9 based nanomedicine by fabricating an angiopep-2 decorated, guanidinium and fluorine functionalized polymeric nanoparticle with loading Cas9/gRNA RNP for the treatment of GBM. The guanidinium and fluorine domains of our polymeric nanoparticles were both capable of interacting with Cas9/gRNA RNP to stabilize it in blood circulation, without impairing its activity. Moreover, by leveraging angiopep-2 peptide functionality, the RNP nanoparticles efficiently crossed the BBB and accumulated in brain tumors. In U87MG cells, we achieved approximately 32% gene knockout and 67% protein reduction in the targeted proto-oncogene polo-like kinase 1 (PLK1). This was sufficient to suppress tumor growth and significantly improved the median survival time of mice bearing orthotopic glioblastoma to 40 days, while inducing negligible side or off-target effects. These results suggest that the developed brain-targeted CRISPR/Cas9 based nanomedicine shows promise for effective human glioblastoma gene therapy.

High expression of HOXA4 in patients with glioma indicates unfavorable clinical outcomes.

HOXA4 is a novel oncogene that has been observed in many kinds of tumors, but its role during glioma carcinogenesis and its clinical significance in diagnosing and prognosis human glioma remains unknown. In the present study, the Chinese Glioma Atlas (CGGA)-RNA sequencing database, CGGA microarray, and The Cancer Genome Atlas (TCGA)-RNA seq data from 1674 glioma patients were obtained from online databases and analyzed using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) to detect changes in the expression level of HOXA4 and characterize the relationship between HOXA4 and the clinical characteristics and prognosis of patients with glioma. Gene set enrichment analysis (GSEA) was used to reveal how HOXA4 regulates tumor-related pathways. HOXA4 mRNA levels in glioma tissue were higher than those in adjacent brain tissue. HOXA4 expression was also closely related to the clinical and molecular characteristics of gliomas, such as tumor grade and isocitrate dehydrogenase (IDH) mutation. Functional enrichment analysis revealed that HOXA4 could regulate cancer-related signal pathways, such as Cell cycle, Cell adhesion molecules cams, and JAK/STAT signaling pathway. Results of in vitro experiments confirmed that knockdown of HOXA4 blocks the cell cycle pathway and inhibits the proliferation, invasion and chemotherapy resistance in gliomas. We concluded that HOXA4 was an independent risk factor for glioma and may have clinical diagnostic potential. Meanwhile, our findings revealed that HOXA4 could be used as a biomarker for glioma diagnosis and treatment.

Cysteine cathepsin C: a novel potential biomarker for the diagnosis and prognosis of glioma.

BACKGROUND: Cysteine cathepsin C encoded by the CTSC gene is an important member of the cysteine cathepsin family that plays a key role regulation of many types of tumors. However, whether CTSC is involved in the pathological process of glioma has not yet been reported. We comprehensively analyzed data from multiple databases and for the first time revealed a role and specific mechanism of action of CTSC in glioma, identifying it as a novel and efficient biomarker for the diagnosis and treatment of this brain tumor. METHODS: The expression of CTSC in glioma and its relationship with clinical characteristics and prognosis of patients with glioma were analyzed at different levels by using clinical sample information from several databases. CTSC expression levels in glioma and normal brain tissues, as well as in glioma cells and normal brain cells, was validated by real-time quantitative polymerase chain reaction (RT-qPCR). Gene set enrichment analysis (GSEA) was used to reveal the signaling pathways that CTSC may participate in. The connectivity map was used to reveal small molecules that may inhibit CTSC expression in glioma, and the putative effect of these compounds was verified by RT-qPCR. RESULTS: Our analyses showed that the expression of CTSC in glioma was higher than that in non-cancerous cells. GSEA showed that CTSC expression may regulate the malignant development of glioma through Toll-like receptor signaling pathways, pathways in cancer, and extracellular matrix receptor interaction signaling pathways. And we proved piperlongumine and scopoletin could inhibit CTSC expression in glioma cells. CONCLUSIONS: CTSC may serve as an efficient molecular target for the diagnosis and therapy of glioma, thereby improving the poor prognosis of patients with glioma.

Effects of ESCO2 or its methylation on the prognosis, clinical characteristics, immune microenvironment, and pathogenesis of low-grade glioma.

The establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) has an important regulatory effect on cell proliferation and division, which is closely related to the malignant process of glioma cells. Therefore, this study attempts to provide a target for biologically targeted therapy for low-grade glioma (LGG) by demonstrating the regulatory effect of ESCO2 during the pathological process of LGG. First, the 1064 samples of LGG transcriptomic data and corresponding clinicopathological information obtained from various databases were included in the study. Second, the chi-squared test showed that the expression of ESCO2 was associated with the malignant characteristics of LGG (recurrence and grade), and Kaplan Meier and multivariate analysis suggested that ESCO2 was an independent risk factor, resulting in a significant reduction in the overall duration of survival of patients. Third, co-expression analysis showed that the level of mRNA expression of ESCO2 was negatively regulated by multiple methylation sites (cg04108328, cg12564175, and cg26534677), and the hypermethylation status of cg12564175 could prolong the overall survival of patients. Fourth, the Tumor Immune Estimation Resource (TIMER) database shows that ESCO2 can have a positive regulatory relationship with six different immune cells, such as CD8 + T cells and macrophages, and a positive expression relationship with PD-1 and PD-L1. Finally, Gene Set Enrichment Analysis (GSEA) showed that ESCO2 may play a carcinogenic role by affecting cell replication and DNA repair. In summary, this study confirmed the carcinogenic effect of ESCO2 on LGG for the first time. It is speculated that both the mRNA of ESCO2 and its methylation site (cg12564175) can be useful biological targets for molecular targeted therapy of LGG.

Post-traumatic brain injury glioma: Characteristics, report of 2 cases report and literature review.

BACKGROUND: Traumatic brain injury (TBI) as a pathogenetic factor in glioma remains controversial, and currently there is still no clear mechanism behind post-TBI glioma. Thus, we provide two case reports of post-TBI glioma contributing power to this research, and we provide a summary of the mechanisms of post-TBI glioma through literature review. METHODS: We report two cases of brain gliomas that developed in the scar of a previous brain trauma. Both patients were male and both had suffered prior traumatic brain injuries (time interval 10-20 years), and postoperative pathological findings reported glioblastoma and WHO grade III glioma, respectively. RESULTS: These two cases further support the association of between traumatic brain injury and gliomas development. CONCLUSION: Although the epidemiological investigation between TBI and glioma is still controversial, there are still some important aspects here that can determine the possibility between TBI and gliomagenesis. Besides, we found that the reparative response of neural stem cells and the dysregulation of inflammatory cells are timportant theories of the mechanism of post-TBI glioma.

Identification of HOXD10 as a Marker of Poor Prognosis in Glioblastoma Multiforme.

PURPOSE: HOXD10 is a tumor modulator that can either be a tumor-suppressor or a tumor-promoting gene. However, the role of HOXD10 in glioblastoma multiforme (GBM) remains unclear. METHODS: Immunohistochemistry (IHC) was applied to detect protein expression of HOXD10 in GBM and normal brain tissue patients. Clinicopathological characteristics with GBM were recorded, and a Kaplan-Meier curve was plotted. Additionally, the mRNA expression of HOXD10 and its effect on prognosis were analyzed using the online tool GEPIA and the Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and the Gene Expression Omnibus (GEO) databases. Based on the mRNA expression of HOXD10, GBM patients from TCGA database were divided into low- and high-HOXD10 expression groups to analyze the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and construct a lncRNA-miRNA-mRNA network and a protein-protein interaction (PPI) network. RESULTS: The mRNA expression of HOXD10 was up-regulated in GBM according to GEPIA, while the protein expression of HOXD10 in GBM was down-regulated according to IHC analysis of samples from patients collected from our hospital. Correlation analysis showed that HOXD10 expression was significantly related to IDH1 status. Univariate analysis revealed that low HOXD10 expression, complete surgical resection, postoperative radiotherapy, postoperative temozolomide chemotherapy and IDH1 mutation were all beneficial prognostic factors. Further multivariate analysis revealed that only complete surgical resection and postoperative radiotherapy were independent prognostic factors. GO and KEGG enrichment analyses indicated that HOXD10 expression is mainly involved in cytokine-cytokine receptor interactions. In the ceRNA network, 89 nodes, containing 45 mRNAs, 39 miRNAs and five lncRNAs associated with prognosis were involved. The PPI network revealed a tight interaction between HOXD10 and HOXD8, HOXD9, HOXD11, HOXD13 and HOXB3. CONCLUSION: Based on our experimental data, although HOXD10 expression is low in GBM compared with normal brain tissue, GBM patients with high HOXD10 expression have a worse prognosis. HOXD10 may play different or even opposite roles in different stages of GBM occurrence and development. For patients with GBM, HOXD10 may be a valid predictor of prognosis.

Cation-Free siRNA Micelles as Effective Drug Delivery Platform and Potent RNAi Nanomedicines for Glioblastoma Therapy.

Nanoparticle-based small interfering RNA (siRNA) therapy shows great promise for glioblastoma (GBM). However, charge associated toxicity and limited blood-brain-barrier (BBB) penetration remain significant challenges for siRNA delivery for GBM therapy. Herein, novel cation-free siRNA micelles, prepared by the self-assembly of siRNA-disulfide-poly(N-isopropylacrylamide) (siRNA-SS-PNIPAM) diblock copolymers, are prepared. The siRNA micelles not only display enhanced blood circulation time, superior cell take-up, and effective at-site siRNA release, but also achieve potent BBB penetration. Moreover, due to being non-cationic, these siRNA micelles exert no charge-associated toxicity. Notably, these desirable properties of this novel RNA interfering (RNAi) nanomedicine result in outstanding growth inhibition of orthotopic U87MG xenografts without causing adverse effects, achieving remarkably improved survival benefits. Moreover, as a novel type of polymeric micelle, the siRNA micelle displays effective drug loading ability. When utilizing temozolomide (TMZ) as a model loading drug, the siRNA micelle realizes effective synergistic therapy effect via targeting the key gene (signal transducers and activators of transcription 3, STAT3) in TMZ drug resistant pathways. The authors' results show that this siRNA micelle nanoparticle can serve as a robust and versatile drug codelivery platform, and RNAi nanomedicine and for effective GBM treatment.

ELK3: A New Molecular Marker for the Diagnosis and Prognosis of Glioma.

ETS transcription factor ELK3 (ELK3), a novel oncogene, affects pathological processes and progression of many cancers in human tissues. However, it remains unclear whether ELK3, as a key gene, affects the pathological process of gliomas and the prognosis of patients with gliomas. This study aimed to comprehensively and systematically reveal the correlation between ELK3 and the malignant progression of gliomas by analyzing clinical sample information stored in multiple databases. We revealed the putative mechanism of ELK3 involvement in malignant gliomas progression and identified a new and efficient biomarker for glioma diagnosis and targeted therapy. Based on the sample data from multiple databases and real-time quantitative polymerase chain reaction (RT-qPCR), the abnormally high expression of ELK3 in gliomas was confirmed. Kaplan-Meier and Cox regression analyses demonstrated that a high ELK3 expression was markedly associated with low patient survival and served as an independent biomarker of gliomas. Wilcox and Kruskal-Wallis tests revealed that expression of ELK3 was positively correlated with several clinical characteristics of patients with gliomas, such as age, WHO classification, and recurrence. Moreover, Cell Counting Kit-8 (CCK-8), immunofluorescence, and wound healing assays confirmed that ELK3 overexpression markedly promoted the proliferation and migration of glioma cells. Finally, gene set enrichment analysis (GSEA) and western blotting confirmed that overexpression of ELK3 regulated the JAK-STAT signaling pathway and upregulate the expression of signal transducer and activator of transcription 3 (STAT3) and phosphorylated STAT3 (P-STAT3) to promote the malignant transition of gliomas. Therefore, ELK3 may serve as an efficient biomarker for the diagnosis and prognosis of gliomas and it can also be used as a therapeutic target to improve the poor prognosis of patients with gliomas.

Internal Jugular Vein Fenestration and Duplication: Anatomical Findings, Prevalence, and Literature Review.

Background: Comprehensive knowledge of the internal jugular vein (IJV) regarding its anatomical variations and the pattern of its course is valuable for preventing unexpected injuries during surgical procedures or central venous access. IJV anatomical anomalies such as fenestration and duplication are rare, mainly represented by case reports, and intraoperative findings. Objective: To present two additional cases of IJV anomalies and highlight its clinical presentation, anatomical characteristics, management, and prevalence through an extensive literature review. Methods and Case Reports: From January 2017 to December 2018, we retrospectively collected data of 221 patients undergoing neck dissection (ND) procedures and identified two patients with IJV anomalies (fenestration and duplication) providing a clinical prevalence of ~0.9%. The IJV fenestration referred to an IJV bifurcation that reunites proximal to the subclavian vein, whereas in the IJV duplication both branches remain separated. In both of our cases, the spinal accessory nerve (SAN) crossed the window between the IJV branches. Conclusion: Anatomical variations are more likely to be identified intraoperatively or incidentally, and due to the risk of SAN and vascular injury, special attention should be taken to identify them preoperatively in order to reduce the risk of iatrogenic injury and unexpected complications.

Nanomedicine-based immunotherapy for central nervous system disorders.

Central nervous system (CNS) disorders represent a broad spectrum of brain ailments with short- and long-term disabilities, and nanomedicine-based approaches provide a new therapeutic approach to treating CNS disorders. A variety of potential drugs have been discovered to treat several neuronal disorders; however, their therapeutic success can be limited by the presence of the blood-brain barrier (BBB). Furthermore, unique immune functions within the CNS provide novel target mechanisms for the amelioration of CNS diseases. Recently, various therapeutic approaches have been applied to fight brain-related disorders, with moderate outcomes. Among the various therapeutic strategies, nanomedicine-based immunotherapeutic systems represent a new era that can deliver useful cargo with promising pharmacokinetics. These approaches exploit the molecular and cellular targeting of CNS disorders for enhanced safety, efficacy, and specificity. In this review, we focus on the efficacy of nanomedicines that utilize immunotherapy to combat CNS disorders. Furthermore, we detailed summarize nanomedicine-based pathways for CNS ailments that aim to deliver drugs across the BBB by mimicking innate immune actions. Overview of how nanomedicines can utilize multiple immunotherapy pathways to combat CNS disorders.

The siRNAsome: A Cation-Free and Versatile Nanostructure for siRNA and Drug Co-delivery.

Nanoparticles show great potential for drug delivery. However, suitable nanostructures capable of loading a range of drugs together with the co-delivery of siRNAs, which avoid the problem of cation-associated cytotoxicity, are lacking. Herein, we report an small interfering RNA (siRNA)-based vesicle (siRNAsome), which consists of a hydrophilic siRNA shell, a thermal- and intracellular-reduction-sensitive hydrophobic median layer, and an empty aqueous interior that meets this need. The siRNAsome can serve as a versatile nanostructure to load drug agents with divergent chemical properties, therapeutic proteins as well as co-delivering immobilized siRNAs without transfection agents. Importantly, the inherent thermal/reduction-responsiveness enables controlled drug loading and release. When siRNAsomes are loaded with the hydrophilic drug doxorubicin hydrochloride and anti-P-glycoprotein siRNA, synergistic therapeutic activity is achieved in multidrug resistant cancer cells and a tumor model.

MiR-218-5p targets LHFPL3 to regulate proliferation, migration, and epithelial-mesenchymal transitions of human glioma cells.

Glioblastoma (GBM) is a main subtype of high-grade gliomas with features in progressive brain tumor. Lipoma HMGIC fusion partner-like 3 (LHFPL3) is reported to be highly expressed in malignant glioma, but the relationship and mechanism between LHFPL3 and tumor is inexplicit. The present study aimed to screen the miRNAs targeting LHFPL3 and verify the pathogenesis and development of gliomas. Bioinformatics software predicted that miR-218-5p and miR-138-5p can specifically bind to LHFPL3 mRNA. And the expression of miR-218-5p and miR-138-5p was down-regulated in glioma cell lines and glioma tissues from the patients compared with the normal cells. While dual luciferase activity experiment confirmed, only miR-218-5p can directly bind to LHFPL3. After miR-218-5p transfection of U251 and U87 cells, cytological examinations found a reduction in cell activity, proliferation and invasive ability. Further study showed that miR-218-5p transfection could inhibit epithelial-mesenchymal transitions (EMT). Therefore, miR-218-5p targeting LHFPL3 mRNA plays significant roles in preventing the invasiveness of glioma cells. The present study also revealed a novel mechanism for miRNA-LHFPL3 interaction in glioma cells, which may be potential targets for developing therapies in treating glioma.

Vertebral Arteriovenous Fistula: A Rare Complication Following Transpedicular Occipitocervical Fixation in a Patient with Atlantoaxial Dislocation.

Vertebral arteriovenous fistula (AVF), a complication of a vertebral artery injury (VAI), is a rare but serious complication of upper cervical spine fixation surgery. We report a case of a 59-year-old female patient who had a vertebral AVF following transpedicular occipitocervical fixation surgery. Endovascular embolization of the AVF was successfully performed using ethylene vinyl alcohol. From this case we learned that preoperative evaluation of the course of the vertebral artery is necessary, and vertebral artery embolism is an effective and safe method to treat vertebral AVF after proof of a patent second vertebral artery.

[Individual surgical treatment of craniocervical junction malformation].

OBJECTIVE: To explore the individual surgical treatment of various performance types of craniocervical junction malformation. METHODS: From January 2011 to December 2013, 112 patients with craniocervical junction malformations were treated at our department, including Chiari malformation (n = 65) (syringomyelia, n = 58 and without syringomyelia, n = 7), basilar invagination disease (n = 35) (with cerebellar tonsillar herniation malformation or occipitocervical fusion) and complex craniocervical malformation (n = 22) (atlantoaxial dislocation with occipitocervical fusion or with chiari malformation or cervical insufficiency sub-section). All of them had the symptoms of upper cervical nerve damage. For those with Chiari malformation, we evaluated atlanto-occipital joint stability preoperatively. If atlanto-occipital joint was stable, we performed small occipital bone window decompression, partial removal of cerebellar tonsils, loosening of posterior fossa, upper cervical adhesions, artificial dura appropriate sutured dural repair expanding neck pillow. For patients with basilar invagination, if nerve compression performance was in the rear, posterior decompression was performed. For those with complex craniocervical malformation with atlantoaxial dislocation, neck traction under anesthesia or traction after anterior release, then pillow neck fixation and fusion were performed. RESULTS: During follow-ups, the symptoms improved significantly (n = 98, 87.51%). There were no symptomatic change (n = 10, 8.93%), postoperative neurological deterioration (n = 3, 2.67%) and death (n = 1, 0.89%). CONCLUSION: According to specific clinical manifestations of craniocervical junction malformation patients, the best treatment is to perform individualized surgeries after thorough preoperative evaluations.