The role of intraoperative neurophysiological monitoring in intramedullary spinal cord tumor surgery.

Intramedullary tumors are a class of central nervous system tumors with an incidence of 2 to 4%. As they are located very deep and frequently cause postoperative neurological complications, surgical resection is difficult. In recent years, many surgeons have performed electrophysiological monitoring to effectively reduce the occurrence of postoperative neurological complications. Modern electrophysiological monitoring technology has advanced considerably, leading to the development of many monitoring methods, such as SSEPs, MEPs, DCM, and EMG, to monitor intramedullary tumors. However, electrophysiological monitoring in tumor resection is still being studied. In this article, we discussed the different monitoring methods and their role in monitoring intramedullary tumors by reviewing previous studies. Intratumorally tumors need to be monitored for a summary of the condition of the patient. Only by using various monitoring methods flexibly and through clear communication between surgeons and neurophysiological experts can good decisions be made during surgery and positive surgical results be achieved.

Lymphoma of the central nervous system originating from the septum pellucidum region: Two case reports with literature review.

RATIONALE: Non-Hodgkin lymphoma affecting the brain, eyes, and cerebrospinal fluid without systemic spread is known as primary central nervous system lymphoma (PCNSL). While intracerebroventricular PCNSL is commonly found in the lateral ventricles and the third and fourth ventricles, the occurrence of PCNSL originating from the septum pellucidum is extremely rare. PATIENT CONCERNS: Two patients presented with recent memory loss and high cranial pressure. DIAGNOSES: Magnetic resonance imaging revealed a clear enhancing lesion in the septum pellucidum region. Pathological examination confirmed that both cases were primary large B-cell lymphoma GCB (germinal center B-cell-like) subtypes located in an "immune-privileged" area. INTERVENTIONS: Both patients underwent total tumor resection, and the procedures were successfully completed without surgical complications. OUTCOMES: Over a 1-year period, treatment included four cycles of high-dose methotrexate combined with temozolomide. During the follow-up period (19-23 months), no recurrence of the lymphoma was observed. LESSONS: In cases of PCNSL in the septum pellucidum, it is crucial to consider it as a potential differential diagnosis for intraventricular tumors. Surgical interventions should focus on maximizing tumor resection while ensuring the protection of critical structures like the fornix and peripheral neural components. The role of surgery compared to biopsy, as well as the long-term complications, necessitates extended follow-up. Additionally, an individualized treatment approach, considering factors such as age, Karnofsky performance score, and organ function assessment, can lead to positive outcomes.

Epidemiology and survival of patients with central nervous system solitary fibrous tumors: A population-based analysis.

Background: The objective of this study was to determine population-based estimates of the epidemiology and prognosis of central nervous system solitary fibrous tumors (cSFTs). Methods: We extracted the data of patients diagnosed with cSFTs between 2004 and 2018 from the Surveillance, Epidemiology, and End Results database. We analyzed the distribution of patients according to their demographic and clinical characteristics. Binary logistic regression analysis was performed to predict which patients would be diagnosed with malignant cSFT. Possible prognostic indicators were analyzed by multivariable Cox proportional hazards models. Results: A total of 650 cases were included. The majority of patients were diagnosed at 50-59 years old, and the median age at diagnosis was 55 years. A total of 13.4% of the tumors were located in the spinal canal, and 24% of the tumors were benign. Most of the tumors were larger than 3 cm, but distant metastasis was rare. Tumor resection was the first choice of treatment for these patients, and total resection was achieved in 51.1%. Radiation therapy after surgery was also administered to 42.3% of the patients. The median survival was 57 months. Intracranial tumors and tumors with distant metastasis tended to be malignant. The results of the log-rank test showed that the patients who underwent total resection had better overall survival (OS), but the effect of radiation therapy after surgery was not significant. Conclusion: cSFT is a rare and aggressive type of tumor. Tumor resection is the first choice for treatment, and radiation therapy after surgery does not improve OS. Patients older than 60 years of age who are diagnosed with intracranial tumors, malignant tumors and distant metastasis have worse OS outcomes than their counterparts.

Breaking Bad: Autophagy Tweaks the Interplay Between Glioma and the Tumor Immune Microenvironment.

Though significant strides in tumorigenic comprehension and therapy modality have been witnessed over the past decades, glioma remains one of the most common and malignant brain tumors characterized by recurrence, dismal prognosis, and therapy resistance. Immunotherapy advance holds promise in glioma recently. However, the efficacy of immunotherapy varies among individuals with glioma, which drives researchers to consider the modest levels of immunity in the central nervous system, as well as the immunosuppressive tumor immune microenvironment (TIME). Considering the highly conserved property for sustaining energy homeostasis in mammalian cells and repeatedly reported links in malignancy and drug resistance, autophagy is determined as a cutting angle to elucidate the relations between glioma and the TIME. In this review, heterogeneity of TIME in glioma is outlined along with the reciprocal impacts between them. In addition, controversies on whether autophagy behaves cytoprotectively or cytotoxically in cancers are covered. How autophagy collapses from its homeostasis and aids glioma malignancy, which may depend on the cell type and the cellular context such as reactive oxygen species (ROS) and adenosine triphosphate (ATP) level, are briefly discussed. The consecutive application of autophagy inducers and inhibitors may improve the drug resistance in glioma after overtreatments. It also highlights that autophagy plays a pivotal part in modulating glioma and the TIME, respectively, and the intricate interactions among them. Specifically, autophagy is manipulated by either glioma or tumor-associated macrophages to conform one side to the other through exosomal microRNAs and thereby adjust the interactions. Given that some of the crosstalk between glioma and the TIME highly depend on the autophagy process or autophagic components, there are interconnections influenced by the status and well-being of cells presumably associated with autophagic flux. By updating the most recent knowledge concerning glioma and the TIME from an autophagic perspective enhances comprehension and inspires more applicable and effective strategies targeting TIME while harnessing autophagy collaboratively against cancer.

Dynamic changes in intramedullary pressure 72 hours after spinal cord injury.

Intramedullary pressure increases after spinal cord injury, and this can be an important factor for secondary spinal cord injury. Until now there have been no studies of the dynamic changes of intramedullary pressure after spinal cord injury. In this study, telemetry systems were used to observe changes in intramedullary pressure in the 72 hours following spinal cord injury to explore its pathological mechanisms. Spinal cord injury was induced using an aneurysm clip at T10 of the spinal cord of 30 Japanese white rabbits, while another 32 animals were only subjected to laminectomy. The feasibility of this measurement was assessed. Intramedullary pressure was monitored in anesthetized and conscious animals. The dynamic changes of intramedullary pressure after spinal cord injury were divided into three stages: stage I (steep rise) 1-7 hours, stage II (steady rise) 8-38 hours, and stage III (descending) 39-72 hours. Blood-spinal barrier permeability, edema, hemorrhage, and histological results in the 72 hours following spinal cord injury were evaluated according to intramedullary pressure changes. We found that spinal cord hemorrhage was most severe at 1 hour post-spinal cord injury and then gradually decreased; albumin and aquaporin 4 immunoreactivities first increased and then decreased, peaking at 38 hours. These results confirm that severe bleeding in spinal cord tissue is the main cause of the sharp increase in intramedullary pressure in early spinal cord injury. Spinal cord edema and blood-spinal barrier destruction are important factors influencing intramedullary pressure in stages II and III of spinal cord injury.

Prevalence and outcome of acute gastrointestinal injury in critically ill patients: A systematic review and meta-analysis.

BACKGROUND: The aim of the study was to investigate the prevalence and impact of acute gastrointestinal injury (AGI) on clinical outcomes in critically ill patients. METHODS: The PubMed, Cochrane, and Embase databases were searched to identify trials that assessed gastrointestinal injury in critically ill patients. Outcome measures were prevalence of AGI among critically ill patients; incidence of mortality among critically ill patients with AGI, and incidence of mortality stratified by severity of AGI. RESULTS: The meta-analysis included 14 studies. The prevalence of AGI in critically ill patients was 40% [95% confidence interval (CI), 27%-54%]; the incidence of mortality among critically ill patients with AGI was 33% (95% CI, 26%-41%). There was a higher risk of mortality in critically ill patients with AGI compared to those without AGI [risk ratio (RR) = 2.01; 95% CI 1.20-3.37, P = .008). Subgroup analyses of studies that defined AGI according to European Society of Intensive Care Medicine (ESICM) criteria confirmed these findings and showed that the risk of mortality was higher in critically ill patients with more severe AGI (ESICM grade III and IV vs grade II) [RR of 1.86 (95% CI 1.48-2.34), P < .00001]. CONCLUSION: AGI is common in critically ill patients, mortality in critically ill patients with AGI is high, and severity of AGI is associated with mortality. The widespread clinical use of standard criteria with a severity gradation will facilitate the diagnosis and management of AGI in critically ill patients.

Newcastle disease virus enhances the growth-inhibiting and proapoptotic effects of temozolomide on glioblastoma cells in vitro and in vivo.

Glioblastoma (GBM) is the most serious and most common brain tumor in humans. Despite recent advances in the diagnosis of GBM and the development of new treatments, the prognosis of patients has not improved. Multidrug resistance, particularly resistance to temozolomide (TMZ), is a challenge in combating glioma, and more effective therapies are needed. Complementary treatment with the LaSota strain of the naturally oncolytic Newcastle disease virus (NDV-LaSota) is an innovation. In our experiments, the combination therapy of NDV-LaSota and temozolomide (TMZ) was more effective than either treatment alone in inducing apoptosis in glioma cells. NDV can function as a tumor cell selective approach to inhibit AKT and activate AMPK. Consequently, mTOR, 4EBP1 and S6K were also suppressed. The combination therapy of NDV and TMZ also significantly extended survival in a rat xenograft tumor model. In conclusion, NDV suppress AKT signaling and enhances antitumor effects of TMZ. Our study provides one of the theoretical basis for the use of a combined therapy of TMZ and NDV, which could benefit GBM patients.

6'-O-Galloylpaeoniflorin Attenuates Cerebral Ischemia Reperfusion-Induced Neuroinflammation and Oxidative Stress via PI3K/Akt/Nrf2 Activation.

6'-O-galloylpaeoniflorin (GPF), a galloylated derivative of paeoniflorin isolated from peony root, has been proven to possess antioxidant potential. In this present study, we revealed that GPF treatment exerted significant neuroprotection of PC12 cells following OGD, as evidenced by a reduction of oxidative stress, inflammatory response, cellular injury, and apoptosis in vitro. Furthermore, treatment with GPF increased the levels of phosphorylated Akt (p-Akt) and nuclear factor-erythroid 2-related factor 2 (Nrf2), as well as promoted Nrf2 translocation in PC12 cells, which could be inhibited by Ly294002, an inhibitor of phosphoinositide 3-kinase (PI3K). In addition, Nrf2 knockdown or Ly294002 treatment significantly attenuated the antioxidant, anti-inflammatory, and antiapoptotic activities of GPF in vitro. In vivo studies indicated that GPF treatment significantly reduced infarct volume and improved neurological deficits in rats subjected to CIRI, as well as decreased oxidative stress, inflammation, and apoptosis, which could be inhibited by administration of Ly294002. In conclusion, these results revealed that GPF possesses neuroprotective effects against oxidative stress, inflammation, and apoptosis after ischemia-reperfusion insult via activation of the PI3K/Akt/Nrf2 pathway.

Dynamic diffusion tensor imaging of spinal cord contusion: A canine model.

This study aimed to explore the dynamic diffusion tensor imaging (DTI) of changes in spinal cord contusion using a canine model of injury involving rostral and caudal levels. In this study, a spinal cord contusion model was established in female dogs using a custom-made weight-drop lesion device. DTI was performed on dogs with injured spinal cords (n=7) using a Siemens 3.0T MRI scanner at pre-contusion and at 3 h, 24 h, 6 weeks and 12 weeks post-injury. The tissue sections were stained for immunohistochemical analysis. Canine models of spinal cord contusion were created successfully using the weight-drop lesion device. The fractional anisotropy (FA) value of lesion epicenter decreased, while the apparent diffusion coefficient (ADC), mean diffusivity (MD), and radial diffusivity (RD) values increased, and the extent of the curve was apparent gradually. The site and time affected the DTI parameters significantly in the whole spinal cord, ADC (site, P < 0.001 and time, P = 0.077, respectively); FA (site, P < 0.001 and time, P = 0.002, respectively). Immunohistological analysis of GFAP and NF revealed the pathologic changes of reactive astrocytes and axons, as well as the cavity and glial scars occurring during chronic SCI. DTI is a sensitive and noninvasive imaging tool useful to assess edema, hemorrhage, cavity formation, structural damage and reconstruction of axon, and myelin in dogs. The DTI parameters after contusion vary. However, the curves of ADC, MD, and RD were nearly similar and the FA curve was distinct. All the DTI parameters were affected by distance and time.

Knockdown of long non-coding RNA ANRIL inhibits proliferation, migration, and invasion but promotes apoptosis of human glioma cells by upregulation of miR-34a.

Gliomas are the most common types of primary central nervous system malignancy found in adults. Long non-coding RNA antisense non-coding RNA in the INK4 locus (ANRIL) variants are associated with glioma and miR-34a is markedly downregulated in U251 glioma cells. The 3'-untranslated region (3'UTR) of silent information regulator 1 (Sirt1) contains a conserved site that is targeted directly by miR-34a. Therefore, in this study, we investigated the roles of ANRIL, miR-34a, and Sirt1 in glioma and their potential interactions. Firstly, expression of ANRIL in normal glia cells and five glioma cell lines was measured. Then, effects of ANRIL suppression on cell proliferation, apoptosis, migration and invasion of U251 cells as well as expression of miR-34a were assessed. Meanwhile, effects of miR-34a on U251 cells silencing ANRIL were tested. Whether Sirt1 is a target of miR-34a was verified, followed by estimating the role of Sirt1 overexpression in U251 cells overexpressing miR-34a. Finally, the involved signaling pathways were assessed. ANRIL was upregulated in glioma cells and its suppression inhibited cell proliferation, migration and invasion but promoted cell apoptosis. ANRIL acted as a sponge of miR-34a, and Sirt1 is a target of miR-34a. Then, Sirt1 was proved to function through activation of the PI3K/AKT and mTOR signaling pathways. In conclusion, ANRIL was upregulated in glioma, and its inhibition could repress cell proliferation, migration and invasion but inhibit cell apoptosis through miR-34a-mediated downregulation of Sirt1, involving the inactivation of the PI3K/AKT and mTOR pathways.

Identification of Driver Genes and Key Pathways of Glioblastoma Shows JNJ-7706621 as a Novel Antiglioblastoma Drug.

OBJECTIVE: The aim of this study is to identify novel targets of diagnosis, therapy, and prognosis for glioblastoma, as well as to verify the therapeutic effect of JNJ-7706621 regarding glioblastoma. METHODS: The gene expression profiles of GSE42656, GSE50161, and GSE86574 were obtained respectively from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified with comparison between gene expression profiles of the glioblastoma tissues and normal tissues. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analyses were performed. Quantitative reverse transcription polymerase chain reaction and survival curve analysis were also conducted to verify the correlation between expression of hub genes and prognosis. Moreover, in vitro, MTT assay, colony-forming assay, the scratch assay, and flow cytometry were performed to verify the therapeutic effect of JNJ-7706621. RESULTS: AURKA, NDC80, KIF4A, and NUSAP1 were identified as hub genes after PPI network analysis. Differential expression of those genes was detected between human normal glial cells and glioblastoma cells by quantitative reverse transcription polymerase chain reaction (P < 0.05), and the survival curve analysis showed that the patients with low expression of gene AURKA, NDC80, KIF4A, and NUSAP1 had a significant favorable prognosis (P < 0.05). In vitro assays showed that JNJ-7706621 inhibited glioblastoma cellular viability, proliferation, and migration via inducing glioblastoma cells apoptosis. CONCLUSIONS: AURKA, NDC80, KIF4A, and NUSAP1 were significantly more highly expressed in glioblastoma cells than in human normal glial cell. Patients with low expression of those 4 genes had a favorable prognosis. JNJ-7706621 was a potential drug in treatment of patients with glioblastoma.

Exosomes derived from gemcitabine-resistant cells transfer malignant phenotypic traits via delivery of miRNA-222-3p.

BACKGROUND: Although gemcitabine-based chemotherapy has been established as a core multimodal therapy for non-small cell lung cancer (NSCLC) treatment, its clinical efficacy remains limited by the development of acquired resistance following tumor metastasis and relapse. In this study, we investigated how gemcitabine-resistant (GR) cells contribute to the development of NSCLC tumor malignancy via exosome-mediated transfer of microRNAs. METHODS: We first studied the mechanism of exosome internalization via PKH-67 staining and an immunofluorescence assay, then confirmed our finding by transmission electron microscopy and western blot analysis. Candidate miRNAs were identified through microarray analysis. Thereafter, RT-PCR, MTS, Transwell and soft agar assays were performed to assess the role of exosomic miR-222-3p in vitro. A 3' untranslated region reporter assay was applied to identify the target of miR-222-3p. A lung metastasis mouse model was constructed to evaluate tumor growth and metastasis in vivo. Finally, clinical samples were used for correlation analysis between exosomic miR-222-3p levels and patients' response to gemcitabine. RESULTS: A549-GR-derived exosomes were internalized by receipt cells via caveolin- and lipid raft-dependent endocytosis, which allowed the transfer of miR-222-3p. Exosomic miR-222-3p enhanced the proliferation, gemcitabine resistance, migration, invasion, and anti-anoikis of parental sensitive cells by directly targeting the promoter of SOCS3. In addition, a higher level of exosomic miR-222-3p in sera usually predicted worse prognosis in NSCLC patients. CONCLUSION: Our data demonstrate that exosomic-miR-222-3p functions as a principal regulator of gemcitabine resistance and malignant characteristics by targeting SOCS3. The exosomic miR-222-3p level in sera may be a potential prognostic biomarker for predicting gemcitabine sensitivity in NSCLC patients.

MicroRNA-10b mediates TGF-ß1-regulated glioblastoma proliferation, migration and epithelial-mesenchymal transition.

Although it is well known that exaggerated proliferation, metastasis and the mesenchymal subtype is related with worst prognoses in glioblastoma (GBM) and that transforming growth factor-ß1 (TGF-ß1) is a potent factor in regulating the proliferation, migration and epithelial-mesenchymal transition (EMT) phenotype of GBM, the detailed mechanisms are still far from elucidated. MicroRNAs (miRNAs) are small non-coding RNAs which play critical roles in various diseases by regulating target gene expression. We report that miR-10b, a molecule downstream of TGF-ß1, is involved in TGF-ß1-regulated GBM cell proliferation, migration and EMT. We found that exposure of GBM cells to TGF-ß1 significantly upregulated miR-10b expression. Overexpression of miR-10b promotes GBM cell proliferation, migration and EMT, whereas depletion of miR-10b obtained reverse effects. Further studies uncovered that some tumor-associated genes including epithelial cadherin (E-cadherin), apoptotic protease activating factor 1 (Apaf-1) and phosphatase and tensin homolog (PTEN) are target genes of miR-10b. In human GBM xenografts, antagomiR directed against miR-10b markedly suppressed tumor growth, and the tumor volume shrunk from 1252.5±285 to 873.4±205 mm3 after antagomiR­10b treatment for 3 weeks compared with the control group (P<0.01). Taken together, our data collectively demonstrate that the proliferation, migration and EMT features of GBM cells can be regulated by TGF-ß1 stimulation through controlling miR-10b. Thus, our findings provide a rationale for targeting TGF-ß1 or miR-10b for the treatment of GBM.