AEBP1 as a potential immune-related prognostic biomarker in glioblastoma: a bioinformatic analyses.

BACKGROUND: Adipocyte enhancer binding protein 1 (AEBP1) has been shown to be closely related to cancer progression; however research on its potential role in glioblastoma (GBM) remains limited. METHODS: Following an expression analysis of AEBP1 in GBM through the Oncomine database, other critical findings were accessed via The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases. Specifically, in addition to identifying differentially expressed genes, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) were further investigated. Additionally, a gene set enrichment analysis (GSEA) was performed to examine the enrichment pathways in the AEBP1 high-expression group. To examine the prognostic role of AEBP1 in GBM, survival information was obtained from the Chinese Glioma Genome Atlas (CGGA) database. Finally, the relationship between the expression of AEBP1 and immune infiltration in GBM was examined by using the "Gene Module", "Survival Module", and "SCNA Module" on the website "Tumor Immune Estimation Resource (TIMER)". RESULTS: The Oncomine database revealed that AEBP1 was highly expressed in GBM. The prognostic analyses of 4 independent databases (i.e., TCGA, GTEx, Oncomine, and CGGA) revealed that AEBP1 was an independent predictable marker of GBM. The results of the GSEA showed that protein export, prion disease, cytokine receptor interaction, hematopoietic cell lineage, cell adhesion molecules, apoptosis, and the complement and coagulation cascades were differentially enriched in highly expressed AEBP1 phenotypes. Hence the conclusion is that the high expression of AEBP1 is closely correlated to poor prognosis of GBM. The immune analysis demonstrated that AEBP1 copy number alteration might affect immune infiltration in GBM tissues, and thus the survival outcomes of GBM patients. CONCLUSIONS: High AEBP1 expression in GBM is closely correlated to patient prognosis. AEBP1 is a potential therapeutic target for the inhibition of cancerous progression and the development of new immunotherapies for GBM.

Modified Full-Endoscopic Interlaminar Discectomy via an Inferior Endplate Approach for Lumbar Disc Herniation: Retrospective 3-Year Results from 321 Patients.

BACKGROUND: Percutaneous endoscopic interlaminar discectomy (PEID) is a widely used minimally invasive procedure that shows satisfying outcomes for the treatment of L5-S1 and even L4-5 disc herniation. PEID can be divided into direct and indirect approaches according to the established method of the working channel. The direct approach mainly uses the puncture needle directly through the intervertebral space into the intervertebral disc under indirect vision and insertion of the guidewire into the puncture needle to guide the dilator and into the working channel to retract the ligamentum flavum, dural sac, and nerve roots. This approach requires a skilled puncture technique, given the high risk of damage to the nerve roots and dural sac. Therefore, we improved this interlaminar access procedure, placing the puncture target at the inferior endplate and performing preoperative epidurography to expose the spinal nerve roots and dural sac after the puncture needle was passed through the ligamentum flavum. We then positioned the puncture needle at the posterior edge of the superior centrum. Finally, we inserted the working sleeve for the operation. This approach is convenient and effectively reduces the learning curve and intraoperative complications. Here we introduce the procedure and report the safety and efficacy of full-endoscopic interlaminar discectomy via an inferior endplate approach for the treatment of lumbar disc herniation. METHODS: We performed full-endoscopic interlaminar discectomy via the inferior endplate approach in 321 patients who met our inclusion criteria between May 2014 and May 2017. All operations were completed under local anesthesia. Under fluoroscopic guidance, we performed epidurography to expose the spinal nerve roots and dural sac. The working sleeve and endoscope were then introduced into the inferior endplate of the superior centrum. Herniated disc material was removed using forceps and a laser under clear endoscopic visualization. We retrospectively evaluated the 321 patients with more than 30 months (range, 12-48 months) of follow-up. The therapeutic effects were assessed using scores of the visual analog scale (VAS), Oswestry disability index (ODI), Macnab standard, and infrared thermal imaging. RESULTS: The mean VAS score for radicular pain improved from 6.3 ± 1.01 preoperatively to 1.01 ± 0.35 at the final follow-up (P < 0.01). The mean ODI score improved from 85.5 ± 12 preoperatively to 12.4 ± 3.7 at the final follow-up (P < 0.01). According to the MacNab standard, the excellent and good outcome scores were 96.5%. The infrared thermal imaging scores indicated significantly improved skin temperature of both lower extremities at 1 week after surgery compared with the preoperation temperature (P < 0.01). CONCLUSIONS: The inferior endplate approach for percutaneous endoscopic interlaminar discectomy provides a safe and effective alternative for the treatment of lumbar disc herniation.

WITHDRAWN: Modified Full-Endoscopic Interlaminar Discectomy via an Inferior Endplate Approach for Lumbar Disc Herniation: Retrospective 3-Year Results from 321 Patients.

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Schwann cell-specific PTEN and EGFR dysfunctions affect neuromuscular junction development by impairing Agrin signaling and autophagy.

The neuromuscular junction (NMJ) is formed by motor nerve terminals, post-junctional muscle membranes, and terminal Schwann cells (SCs). The formation of NMJ requires complex and dynamic molecular interactions. Nerve- and muscle-derived molecules have been well characterized but the mechanistic involvement of SC in NMJ development remains poorly understood. SC-specific phosphatase and tensin homolog (Pten) inactivation and epidermal growth factor receptor (EGFR) overexpression (Dhh-Cre; Cnp-EGFR; Ptenflox/flox or DET) mice were used and NMJ malformation was observed in these mice. Acetylcholine receptors (AChRs) were distorted and varicose presynaptic nerve terminals appeared in the tibialis anterior (TA) muscle of DET mice. Agrin signaling related to NMJ development, was downregulated in TA muscle. Both RAS/MEK/ERK and PI3K/AKT/mTOR signaling pathways were activated in the sciatic nerves of DET mice. In addition, autophagy was downregulated in these sciatic nerves. Interestingly, the use of Torin 2, an mTOR inhibitor, rescued the phenotype. The downregulated-autophagy might account for Agrin signaling abnormity, which induced NMJ malformation. Taken together, our results indicate that SCs-specific Pten and EGFR cooperation are essential for NMJ development.

The combination of NVP-BEZ235 and rapamycin regulates nasopharyngeal carcinoma cell viability and apoptosis via the PI3K/AKT/mTOR pathway.

Nasopharyngeal carcinoma (NPC) is a rare malignancy with a remarkable geographical distribution. Regarding NPC treatment, improving the survival rate of advanced patients seems promising. Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway deregulation is closely associated with tumorigenesis. In the present study, the NPC cell line SUNE1 was divided into four groups: Control, NVP-BEZ235, rapamycin, and NVP-BEZ235+rapamycin. SUNE1 cells in the NVP-BEZ235 group were incubated with NVP-BEZ235; cells in the rapamycin group were incubated with rapamycin, whereas the NVP-BEZ235+rapamycin group refers to SUNE1 cells incubated with a mixture of NVP-BEZ235 and rapamycin. The control group was treated with the same amount of vehicle. Morphological, MTT, terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling and flow cytometry assays demonstrated that NVP-BEZ235 and rapamycin caused morphological changes, inhibited cell viability and induced cellular apoptosis. In addition, reverse transcription-quantitative polymerase chain reaction and western blot revealed that the combination of NVP-BEZ235 and rapamycin affected the activation of the PI3K/AKT/mTOR pathway. The combination of NVP-BEZ235 and rapamycin significantly improved the effect of the drug therapy. The potential underlying mechanism may comprise the joint effects of inhibiting cell viability, promoting cellular apoptosis and reducing relative signal protein expression levels in SUNE1 cells. These findings provided novel evidence that NVP-BEZ235 suppresses NPC development, and indicated a promising potential application of combination drug therapy (NVP-BEZ235+rapamycin) for the clinical treatment of NPC.