Factors influencing postoperative visual improvement in 208 patients with tuberculum sellae meningiomas.

OBJECTIVE: Tuberculum sellae meningiomas (TSMs) usually compress the optic nerve and optic chiasma, thus affecting vision. Surgery is an effective means to remove tumors and improve visual outcomes. On a larger scale, this study attempted to further explore and confirm the factors related to postoperative visual outcomes to guide the treatment of TSMs. METHODS: Data were obtained from 208 patients with TSMs who underwent surgery at our institution between January 2010 and August 2022. Demographics, ophthalmologic examination results, imaging data, extent of resection, radiotherapy status, and surgical approaches were included in the analysis. Univariate and multivariate logistic regressions were used to assess the factors that could lead to favorable visual outcomes. RESULTS: The median follow-up duration was 63 months, and gross total resection (GTR) was achieved in 174 (83.7%) patients. According to our multivariate logistic regression analysis, age < 60 years (odds ratio [OR] = 0.310; P = 0.007), duration of preoperative visual symptoms (DPVS) < 10 months (OR = 0.495; P = 0.039), tumor size ≤ 27 mm (OR = 0.337; P = 0.002), GTR (OR = 3.834; P = 0.006), and a tumor vertical-to-horizontal dimensional ratio < 1 (OR = 2.593; P = 0.006) were found to be significant independent predictors of favorable visual outcomes. CONCLUSION: Age, DPVS, tumor size, GTR, and the tumor vertical-to-horizontal dimensional ratio were found to be powerful predictors of favorable visual outcomes. This study may help guide decisions regarding the treatment of TSMs.

Photoinduced Metal- and Photosensitizer-Free Decarbonylative C-H Alkylation of Cyclic Sulfamidate Imines.

Photoinduced decarbonylative C-C bond formation with readily accessible aldehydes as alkyl sources is described. This protocol provides a sustainable alternative for the effective construction of diverse valuable 4-alkylated sulfonyl ketimines under metal- and photosensitizer-free conditions. Significantly, in this reaction, air serves as the green oxidant, and cyclic sulfamidate imines play a dual role of substrate and photocatalyst, thus affording a concise reaction system for C-H alkylation of cyclic sulfamidate imines.

Delving into the Molecular World of Single Ventricle Congenital Heart Disease.

PURPOSE OF REVIEW: Given a general lack of emphasis on the molecular underpinnings of single ventricle (SV) congenital heart diseases (CHD), our review highlights and summarizes recent advances in uncovering the genetic and molecular mechanisms in SV CHD etiology. RECENT FINDINGS: While common SV-associated genetic mutations were found in key cardiac transcription factors, other mutations were sporadic. With advances in genetic sequencing technologies and animal models, more disease-associated factors have been identified to act in critical cardiac signaling pathways such as NOTCH, Wnt, and TGF signaling. Recent studies have also revealed that different cardiac lineages play different roles in disease pathogenesis. SV defects are attributed to complex combinations of genetic mutations, indicating that sophisticated spatiotemporal regulation of gene transcription networks and functional cellular pathways govern disease progression. Future studies will warrant in-depth investigations into better understanding how different genetic factors converge to influence common downstream cellular pathways, resulting in SV abnormalities.

Glioma exosomal microRNA-148a-3p promotes tumor angiogenesis through activating the EGFR/MAPK signaling pathway via inhibiting ERRFI1.

BACKGROUND: Glioma is the most frequent and lethal primary brain malignancy. Amounting evidence has highlighted the importance of exosomal microRNAs (miRNAs or miRs) in this malignancy. This study aimed to investigate the regulatory role of exosomal miR-148a-3p in glioma. METHODS: Bioinformatics analysis was firstly used to predict the target genes of miR-148a-3p. Exosomes were then extracted from normal human astrocytes and glioma cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to determine the expression patterns of miR-148a-3p and ERBB receptor feedback inhibitor 1 (ERRFI1). Dual-luciferase reporter gene assay was applied to verify the direct binding between miR-148a-3p and ERRFI1. Cell counting kit-8 and tube formation assays were further conducted to assess the proliferation and angiogenic properties of human umbilical vein endothelial cells (HUVECs) in the co-culture system with exosomes. Lastly, glioma tumor models were established in BALB/c nude mice to study the role of exosomal miR-148a-3p in vivo. RESULTS: miR-148a-3p was highly expressed, while ERRFI1 was poorly expressed in glioma. miR-148a-3p was found to be enriched in glioma cells-derived exosomes and could be transferred to HUVECs via exosomes to promote their proliferation and angiogenesis. ERRFI1 was identified as a target gene of miR-148a-3p. In addition, miR-148a-3p activated the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling pathway by inhibiting ERRFI1. In the co-culture system, our data demonstrated that glioma cells-derived exosomal miR-148a-3p down-regulated ERRFI1 and activated the EGFR/MAPK signaling pathway, so as to promote cell proliferation and angiogenesis. In vivo experimentation further demonstrated that this mechanism was responsible for the promotive role of exosomal miR-148a-3p in tumorigenesis and angiogenesis. CONCLUSION: Taken together, glioma-derived exosomal miR-148a-3p promoted tumor angiogenesis through activation of the EGFR/MAPK signaling pathway by ERRFI1 inhibition.

Anatomic Study of Posterior Communicating Artery in Computed Tomographic Image.

PURPOSE: This study aims to provide an anatomic data of posterior communicating artery (PComA) and its anatomic relationship to the adjacent structures, so as to guide surgeons in the surgery of internal carotid artery-posterior communicating artery aneurysm clipping and sellar tumors resection without injuring the PComA. METHODS: Computer topographic angiography images of 123 individuals were reviewed, and the measurements were done on coronal, sagittal, axial, and other user-defined planes after multiplanar reconstruction. Posterior communicating artery was classified in the reconstructed three-dimensional image, measured in proper planes, and located by the structures such as anterior clinoid process (ACP), posterior clinoid process (PCP), and sagittal midline. RESULTS: Six types of PComA were identified in this study based on its existence and origin. The initial part of PComA can be located by ACP, PCP, and sagittal midline based on some particular angles and distances. CONCLUSIONS: Posterior communicating artery varies in different individuals, and the radiologic study of it is an optimal way to analyze the variances. The anatomic relations between PComA and basic skull structures such as the ACP and PCP are especially important for neurosurgeons.

Improving precision management of anxiety disorders: a Mendelian randomization study targeting specific gut microbiota and associated metabolites.

Background: There is growing evidence of associations between the gut microbiota and anxiety disorders, where changes in gut microbiotas may affect brain function and behavior via the microbiota-gut-brain axis. However, population-level studies offering a higher level of evidence for causality are lacking. Our aim was to investigate the specific gut microbiota and associated metabolites that are closely related to anxiety disorders to provide mechanistic insights and novel management perspectives for anxiety disorders. Method: This study used summary-level data from publicly available Genome-Wide Association Studies (GWAS) for 119 bacterial genera and the phenotype "All anxiety disorders" to reveal the causal effects of gut microbiota on anxiety disorders and identify specific bacterial genera associated with anxiety disorders. A two-sample, bidirectional Mendelian randomization (MR) design was deployed, followed by comprehensive sensitivity analyses to validate the robustness of results. We further conducted multivariable MR (MVMR) analysis to investigate the potential impact of neurotransmitter-associated metabolites, bacteria-associated dietary patterns, drug use or alcohol consumption, and lifestyle factors such as smoking and physical activity on the observed associations. Results: Bidirectional MR analysis identified three bacterial genera causally related to anxiety disorders: the genus Eubacterium nodatum group and genus Ruminococcaceae UCG011 were protective, while the genus Ruminococcaceae UCG011 was associated with an increased risk of anxiety disorders. Further MVMR suggested that a metabolite-dependent mechanism, primarily driven by tryptophan, tyrosine, phenylalanine, glycine and cortisol, which is consistent with previous research findings, probably played a significant role in mediating the effects of these bacterial genera to anxiety disorders. Furthermore, modifying dietary pattern such as salt, sugar and processed meat intake, and adjusting smoking state and physical activity levels, appears to be the effective approaches for targeting specific gut microbiota to manage anxiety disorders. Conclusion: Our findings offer potential avenues for developing precise and effective management approaches for anxiety disorders by targeting specific gut microbiota and associated metabolites.

Deciphering Endothelial and Mesenchymal Organ Specification in Vascularized Lung and Intestinal Organoids.

To investigate the co-development of vasculature, mesenchyme, and epithelium crucial for organogenesis and the acquisition of organ-specific characteristics, we constructed a human pluripotent stem cell-derived organoid system comprising lung or intestinal epithelium surrounded by organotypic mesenchyme and vasculature. We demonstrated the pivotal role of co-differentiating mesoderm and endoderm via precise BMP regulation in generating multilineage organoids and gut tube patterning. Single-cell RNA-seq analysis revealed organ specificity in endothelium and mesenchyme, and uncovered key ligands driving endothelial specification in the lung (e.g., WNT2B and Semaphorins) or intestine (e.g., GDF15). Upon transplantation under the kidney capsule in mice, these organoids further matured and developed perfusable human-specific sub-epithelial capillaries. Additionally, our model recapitulated the abnormal endothelial-epithelial crosstalk in patients with FOXF1 deletion or mutations. Multilineage organoids provide a unique platform to study developmental cues guiding endothelial and mesenchymal cell fate determination, and investigate intricate cell-cell communications in human organogenesis and disease. Highlights: BMP signaling fine-tunes the co-differentiation of mesoderm and endoderm.The cellular composition in multilineage organoids resembles that of human fetal organs.Mesenchyme and endothelium co-developed within the organoids adopt organ-specific characteristics.Multilineage organoids recapitulate abnormal endothelial-epithelial crosstalk in FOXF1-associated disorders.

Retrieval practice may not benefit mathematical word-problem solving.

The retrieval practice effect refers to the fact that one or even multiple retrievals of memory content during the same period are more effective than repeated studying to promote future memory retention. It is effective for numerous declarative knowledge learning materials. However, studies have demonstrated that retrieval practice does not benefit problem-solving skill learning. This study used worked examples from math word problem tasks as learning materials, considering the retrieval difficulty as the main factor. Experiment 1 explored the effect of retrieval practice on acquiring problem-solving skills under different initial testing difficulties. Experiment 2 manipulated the difficulty of materials as a variable to ascertain the effect of retrieval practice on problem-solving skills under different material difficulty levels. Experiment 3 introduced feedback variables to facilitate the generation of the retrieval practice effect and examined the effects of various difficulty feedback levels on problem-solving skills learning. Results showed that, compared with restudying examples (SSSS), the example-problem pairs (STST) did not promote delayed test performance. As for the retrieval practice effect, as no differences or advantages were found in the repeated study group on the immediate test, the retrieval practice group generally outperformed the repeated study group on the delayed test. However, across the three experiments, we found no evidence of retrieval practice affecting results during an enhanced delayed test. Therefore, there may be no retrieval practice effect on acquiring problem-solving skills from worked examples.

Endocardium in Hypoplastic Left Heart Syndrome: Implications from In Vitro Study.

Endocardium lines the inner layer of the heart ventricle and serves as the source of valve endothelial cells and interstitial cells. Previously, endocardium-associated abnormalities in hypoplastic left heart syndrome (HLHS) have been reported, including endocardial fibroelastosis (EFE) and mitral and aortic valve malformation. However, few mechanistic studies have investigated the molecular pathological changes in endocardial cells. Recently, the emergence of a powerful in vitro system-induced pluripotent stem cells (iPSCs)-was applied to study various genetic diseases, including HLHS. This review summarized current in vitro studies in understanding the endocardial pathology in HLHS, emphasizing new findings of the cellular phenotypes and underlying molecular mechanisms. Lastly, a future perspective is provided regarding the better recapitulation of endocardial phenotypes in a dish.

GDNF regulates lipid metabolism and glioma growth through RET/ERK/HIF­1/SREBP­1.

Cancer cells rewire their metabolism to meet the demands of growth and survival and this metabolic reprogramming has been recognized as an emerging hallmark of cancer. However, the respective mechanisms remain elusive and the contribution of aberrant lipid metabolism to the malignant phenotypes of glioma are unclear. The present study demonstrated that glial­derived neurotrophic factor (GDNF) is highly expressed in glioma and associated with poor clinical outcomes. In addition, there was a significant correlation between GDNF/rearranged during transfection (RET)/ERK signaling and sterol regulatory element­binding protein­1 (SREBP­1) expression in glioma cells. Pharmacological or genetic inhibition of GDNF­induced RET/ERK activity downregulated SREBP­1 expression and SREBP­1­mediated transcription of lipogenic genes. Additionally, GDNF regulated SREBP­1 activity by promoting hypoxia­inducible factor­1α (HIF­1α) mediated glucose absorption and hexosamine biosynthetic pathway mediated SREBP cleavage­activating protein N­glycosylation. In addition, the inhibition of SREBP­1 reduced the in vitro GDNF­induced glioma cell proliferation. The results elucidated the complex relationship between GDNF/RET/ERK signaling and dysregulated glycolipid­metabolism, which shows great potential to uncover novel metabolic vulnerabilities and improve the efficacy of targeted therapies.

[Bipolar transurethral resection of the prostate versus monopolar transurethral prostatectomy: a pathological study in a canine model].

OBJECTIVE: To compare the postoperative depths of the coagulation zones and pathological changes between bipolar transurethral resection of the prostate with plasmakinetic energy (PKRP) and monopolar transurethral prostatectomy (TURP) in canines. METHODS: Twenty-five male dogs were randomly divided into a PKRP group (n = 12), a TURP group (n = 12) and a sham-operation control group (n = 1). The dogs were sacrificed, their prostates harvested at 0 week (immediately after surgery), 1 week, 2 weeks and 8 weeks postoperatively and sectioned for pathologic analysis and measurement of the coagulation zones. RESULTS: At 0, 1 and 2 weeks after the operation, the coagulation depths were (237.73 +/- 20.12) microm, (113.03 +/- 16.65) microm and (106.01 +/- 16.36) microm in the PKRP group, and (200.75 +/-19.34) microm, (129.46 +/- 17.81) microm and (116.04 +/- 25.67) microm in the TURP group (P < 0.01). At 8 weeks, the coagulation zones completely peeled off and the wounds were covered by regenerated urothelial in both of the groups. At 0, 1, 2 and 8 weeks, different inflammatory reactions were observed in the prostates of the PKRP and TURP groups, with some glandular lumens beneath the coagulation zones expanded and epithelia damaged. However, none of these phenomena occurred in the sham-operation control group. CONCLUSION: Pathologically, PKRP and TURP inflicted basically similar effects on the prostate of the canine. However, the coagulation zone was deeper intraoperatively and became thinner postoperatively with the former than with the latter, which suggests that PKRP causes less bleeding and less penetrative thermal damage than TURP.

Inhibition of NF-κB results in anti-glioma activity and reduces temozolomide-induced chemoresistance by down-regulating MGMT gene expression.

The introduction of temozolomide (TMZ) has improved chemotherapy for malignant gliomas. However, many gliomas are refractory to TMZ, so there is a pressing need for more effective therapeutic options. Here we demonstrated that glioma specimens and cell lines have constitutively high levels of nuclear factor κB (NF-κB) activity. Notably, the expression levels of this transcription factor correlated with malignant grades in glioblastoma multiforme (GBM) and inversely correlated with overall survival. Conversely, knockdown of NF-κB inhibits glioma cell proliferation and treating a panel of established glioma cell lines with pharmacological NF-κB inhibitors markedly decreased glioma viability, led to S cell cycle arrest, and induced apoptosis. We also found a significant correlation between NF-κB expression and O6-methylguanine-DNA methyltransferase (MGMT) expression in gliomas with different origins, and immunohistochemistry confirmed these findings. Genetic or pharmacological (especially parthenolide) inhibition of NF-κB activity down-regulated MGMT gene expression and substantially restored TMZ chemosensitivity in vitro and in vivo. Importantly, the TMZ sensitizing effect of siNF-κB(p65) or parthenolide were rescued by MGMT cDNA expression. These findings suggest that NF-κB is a potential target for inducing cell death in gliomas. A targeted combination strategy in which the response to TMZ is synergistically enhanced by the addition of parthenolide which may be useful, especially in chemoresistant gliomas with high MGMT expression.

Dual blocking of PI3K and mTOR signaling by NVP-BEZ235 inhibits proliferation in cervical carcinoma cells and enhances therapeutic response.

NVP-BEZ235 is a novel dual PI3K/mTOR inhibitor that shows dramatic effects on many tumors, but its effects on cervical carcinoma cells are largely unknown. In the present study, we investigated the effects of NVP-BEZ235 on the proliferation and invasion of cervical carcinoma cells in vitro and clarified its mechanism of action. In cellular settings with human cervical carcinoma cell lines, this molecule effectively and specifically blocked dysfunctional PI3K/mTOR pathway activation, suppressed cell growth in a time- and concentration-dependent manner, led to G1 cell cycle arrest, and induced apoptosis. NVP-BEZ235 suppressed HeLa cell invasiveness and metastasis by inhibiting the PI3K/Akt/MMP-2 pathway. We further demonstrated that NVP-BEZ235 treatment in combination with cisplatin or carboplatin induced a synergistic anti-tumoral response in cervical carcinoma cells. These findings suggested that NVP-BEZ235 could regulate growth and invasion of cervical carcinoma cells; thus it may provide a potential therapy for cervical carcinoma.

[Changes of nuclear factor-kappa gene binding expression in and apoptosis of spermatogenic epithelial cells in the restored testis after torsion: experiment with rats].

OBJECTIVE: To investigate the changes of nuclear factor-kappa gene binding (NF-kappaB) expression in and apoptosis of spermatogenic epithelial cells in the restored testis after torsion and analyze the relationship between them. METHODS: Sixteen male SD rats underwent torsion of the left testis clockwise at an angle of 720 degrees for 2 hours and then the testis was restored to the original position and fixed. Then the 16 rats were randomly divided into 2 equal group: Group I in which salicylazosulfapyridium (SASP) suspension was infused intra-gastrically 5 h after operation and then once a day for 4 times, and Group II in which normal saline (NS) was infused in the same manner. Eight rats (Group III) underwent sham operation and then infused with NS in the same manner as that of Group II. Three days after operation the rats were killed and the samples of the testes at the torsion side were taken out and the seminiferous tubules were isolated. Western blotting was used to detect the NF-kappaB expression in the cytoplasm and nucleus of spermatogenic epithelial cells. Immunohistochemistry was used to detect the in situ expression of NF-kappaB. The apoptosis of the spermatogenic epithelial cells was examined by TUNEL method. RESULTS: Western blotting showed that the NF-kappaB expression in the cytoplasm of spermatogenic epithelial cells of Group II was 9.4 +/- 2.68, somewhat lower, but not significantly, than those of Group I and III (12 +/- 2.2 and 11.1 +/- 3 respectively, both P > 0.05). The NF-kappaB expression in the nucleus of spermatogenic epithelial cells of Group II was 21.1 +/- 3.6, significantly higher than those of Group I and III (8.4 +/- 3.1 and 6.0 +/- 2.3 respectively, both P < 0.05). However, there were no significant differences in the NF-kappaB expression in the cytoplasm and nucleus of spermatogenic epithelial cells between Groups I and III. The NF-kappaB activity coefficient of spermatogenic epithelial cells of Group II was 2.32 +/- 0.4, significantly higher than those of Groups I and III (0.68 +/- 0.3 and 0.52 +/- 0.1 respectively, both P < 0.01). However, there was no significant difference in the NF-kappaB activity coefficient of spermatogenic epithelial cells between Groups I and III (P > 0.05). The NF-kappaB positive cell rate of Group II was 66.1% +/- 3.8%, significantly higher than those of Groups I and III (15.6% +/- 2.6% and 10.8% +/- 2.7%, both P < 0.01). The apoptotic cell rate of Group II was 37.2% +/- 3.3%, significantly higher than those of Groups I and III (7.7% +/- 2.0% and 5.9% +/- 1.7%, both P < 0.01). CONCLUSION: After the torsion of testis, NF-kappaB was activated and released from the nucleus into the cytoplasm, thus initiating the apoptosis of spermatogenic epithelial cells.

[Effects of experimental varicocele on the apoptosis of epididymis epithelium and synthesizing function of the epididymis in rats].

OBJECTIVE: To study the relationships of experimental varicocele to the apoptosis of epididymis epithelium and changes of the contents of alpha-1,4-glucosidase and sialic acid from the unilateral epididymis in adolescent rats, and to investigate the effects of varicocele on the unilateral epididymis epithelium. METHODS: Experimental left varicocele models of 16 adult male Sprague-Dawley rats were obtained by partial ligation of the left renal vein. The epididymides were collected for detecting the apoptosis of epididymis epithelium and the contents of alpha-1,4-glucosidase and sialic acid by using spectrophotometry. RESULTS: Seven days after the establishment of the left varicocele model, the index of the apoptosis of the left epididymis epithelium was significantly higher (P < 0.001) and the contents of alpha-1,4-glucosidase and sialic acid significantly lower (P < 0.05, P < 0.005) in the experimental group than in the control. CONCLUSION: The results suggest that unilateral varicocele may increase the apoptosis of epididymis epithelium and the contents of alpha-1,4-glucosidase and sialic acid and subsequently affect the synthesizing and secretory function of the epididymis.

Giant recurrent dumbbell-shaped hypoglossal schwannoma in an elderly male: A case report.

Dumbbell-shaped hypoglossal Schwannomas of the 12th cranial nerve are extremely rare, and complete removal of these tumors is difficult, particularly in elderly patients with recurrent tumors. The present study reports the case of a 61-year-old male with a giant recurrent dumbbell-shaped hypoglossal schwannoma that arose extracranially. The recurrent tumor was completely removed in a one-stage surgical procedure via the far lateral suboccipital approach in combination with the transcervical approach. To the best of our knowledge, such a lesion has not been reported previously. The life expectancy and natural course of the disease are important factors to take into account when considering the individual end-point of surgery in patients. More studies on hypoglossal schwannomas are required, particularly cases in which the hypoglossal schwannoma was not totally resected, not only in order to develop more definitive and secure surgical treatments, but also to reduce the resultant unnecessary suffering of patients.

Temozolomide in combination with metformin act synergistically to inhibit proliferation and expansion of glioma stem-like cells.

Glioblastoma is the most common and most aggressive brain tumor in adults. The introduction of temozolomide (TMZ) has advanced chemotherapy for malignant gliomas, but it is not curative. The difficulties in treating glioblastoma may be as a result of the presence of glioma stem cells (GSCs), which are a source of relapse and chemoresistance. Another reason may be that endogenous Akt kinase activity may be activated in response to clinically relevant concentrations of TMZ. Akt activation is correlated with the increased tumorigenicity, invasiveness and stemness of cancer cells and overexpression of an active form of Akt increases glioma cell resistance to TMZ. Mounting evidence has demonstrated that cancer stem cells are preferentially sensitive to an inhibitor of Akt and down-regulation of the PI3K/Akt pathway may enhance the cytotoxicity of TMZ. Metformin (MET), the first-line drug for treating diabetes, it has been proved that it reduces AKT activation and selectively kills cancer stem cells, but whether it can potentiate the cytotoxicity of TMZ for GSCs remains unknown. In the present study, the GSCs isolated from human glioma cell line U87 and Rat glioma cell line C6, in vitro treatment with TMZ either alone or with MET. The present study demonstrates that MET acts synergistically with TMZ in inhibiting GSCs proliferation and generating the highest apoptotic rates when compared to either drug alone. These findings implicate that GSCs cytotoxicity mediated by TMZ may be stimulated by MET, have a synergistic effect, but the definite mechanisms remain elusive.

Efficacy and safety of bevacizumab for the treatment of glioblastoma.

Glioblastoma (GBM) is the most common and devastating primary malignant intracranial tumor in adults. The current first-line treatment for patients with newly diagnosed GBM is surgical resection followed by radiotherapy plus concomitant and adjuvant temozolomide. This treatment protocol may prolong the survival period of the patient, however it is not curative and more effective therapeutic strategies are required. GBM is a type of highly vascularized tumor with increased expression levels of vascular endothelial growth factor (VEGF), which is a significant mediator of angiogenesis. Since angiogenesis is essential for tumor growth, anti-angiogenic therapies hold potential for the treatment of GBM, and targeting VEGF has demonstrated promising results in previous studies. Bevacizumab (BEV) is a recombinant humanized monoclonal antibody that inhibits VEGF and is approved by the US Food and Drug Administration as a monotherapy treatment for patients with recurrent GBM and is associated with manageable toxicity. Previous studies have demonstrated that BEV may be an effective treatment for recurrent GBM, with prolonged progression-free survival and overall survival, and maintained patient quality of life and functional status. The present review article briefly outlines the mechanism of action of BEV and summarizes the current literature and clinical trial research on the role of BEV for the treatment of patients with recurrent and newly diagnosed GBM.