BACKGROUND:Besides the hallmark of H3K27M mutation, aberrant amplifications of receptor tyrosine kinases (RTKs) are commonly observed in diffuse midline glioma (DMG), a highly malignant brain tumor with dismal prognosis. Here, we intended to evaluate the efficacy and safety of a multitarget RTK inhibitor anlotinib in patients with H3K27M-DMG.METHODS:A total of 40 newly diagnosed H3K27M-DMG patients including 15 with anlotinib and 25 without anlotinib treatment were retrospectively enrolled in this cohort. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed and compared.RESULTS:The median PFS and OS of all patients in this cohort were 8.5 months (95% CI, 6.5-11.3) and 15.5 months (95% CI, 12.6-17.1), respectively. According to the Response Assessment in Neuro-Oncology (RANO) criteria, the disease control rate in the anlotinib group [93.3%, 95% confidence interval (CI), 70.2-98.8] was significantly higher than those without anlotinib (64%, 95% CI: 40.5-79.8, p = 0.039). The median PFS of patients with and without anlotinib was 11.6 months (95% CI, 7.8-14.3) and 6.4 months (95% CI, 4.3-10.3), respectively. Both the median PFS and OS of DMG patients treated with anlotinib were longer than those without anlotinib in the infratentorial patients (PFS: 10.3 vs. 5.4 months, p = 0.006; OS: 16.6 vs. 8.7 months, p = 0.016). Multivariate analysis also indicated anlotinib (HR: 0.243, 95% CI: 0.066-0.896, p = 0.034) was an independent prognosticator for longer OS in the infratentorial subgroup. In addition, the adverse events of anlotinib administration were tolerable in the whole cohort.CONCLUSIONS:This study first reported that anlotinib combined with Stupp regimen is a safe and feasible regimen for newly diagnosed patients with H3K27M-DMG. Further, anlotinib showed significant efficacy for H3K27M-DMG located in the infratentorial region.

Objective: Investigate the impact of diaphragm sellae competence on surgical outcomes and risk factors for postoperative hypothalamic injury (HI) in patients undergoing endoscopic transsphenoidal surgery (ETS) for infra-diaphragmatic craniopharyngiomas (ICs). Methods: A retrospective analysis of 54 consecutive patients (2016-2023) with ICs treated by ETS was conducted. All tumors originated from the sellar region inferior to the diaphragm sellae and were classified into two subtypes in terms of diaphragm sellae competence: IC with competent diaphragm sellae (IC-CDS) and IC with incompetent diaphragm sellae (IC-IDS). Clinical features, intraoperative findings, and follow-up data were compared between subtypes. Postoperative HI was assessed using a magnetic resonance imaging-based scoring system. Results: Fifty-four patients (29 males, 25 females) were included in this study, with 12 (22.2%) under 18 years old. Overall, 35 cases were IC-CDS, while 19 were IC-IDS. Compared with IC-CDS, patients with IC-IDS tended to have hormone hypofunction before surgery (p = 0.03). Tumor volume in IC-IDS group (9.0 ± 8.6 cm3) was also higher than that in IC-CDS group (3.3 ±3.4 cm, p = 0.011). Thirty-seven patients underwent standard endoscopic transsphenoidal approach (SEA) and 17 underwent an extended endoscopic transsphenoidal approach (EEA). Gross total resection (GTR) was achieved in 50 cases (92.6%). Postoperative CSF leak was observed in four patients (7.4%). Permanent diabetes insipidus (DI) occurred in 13 patients (27.7%), six in IC-CDS and seven in IC-IDS. Postoperative HI occurred in 38.9% of patients. Univariate analysis revealed that large tumor size (p = 0.014), prior hypopituitarism (p = 0.048) and IC-IDS (p < 0.001) were significantly associated with postoperative HI. Multivariate analysis revealed that IC- IDS was the sole predictor of postoperative HI. Conclusion: To our knowledge, this is the largest case series in the literature to describe IC resected by endoscopic surgery in a single institution. Classification based on diaphragm sellae competence highlights distinct clinical features and surgical outcomes between IC-CDS and IC-IDS subtypes. Notably, IC-IDS is an independent risk factor for postoperative HI. Preoperative identification of subtype can guide surgical strategy and potentially minimize complications.

Diffuse gliomas in adults are highly infiltrative and largely incurable. Whole exome sequencing (WES) has been demonstrated very useful in genetic analysis. Here WES was performed to characterize genomic landscape of adult-type diffuse gliomas to discover the diagnostic, therapeutic and prognostic biomarkers. Somatic and germline variants of 66 patients with adult-type diffuse gliomas were detected by WES based on the next-generation sequencing. TCGA and CGGA datasets were included to analyze the integrated diagnosis and prognosis. Among 66 patients, the diagnosis of 9 cases was changed, in which 8 cases of astrocytoma were corrected into IDH-wildtype glioblastoma (GBM), and 1 oligodendroglioma without 1p/19q co-deletion into astrocytoma. The distribution of mutations including ATRX/TP53 differed in three cohorts. The genetic mutations in GBM mainly concentrated on the cell cycle, PI3K and RTK pathways. The mutational landscape of astrocytoma was more similar to that of GBM, with the highest frequency in germline variants. Patients with IDH-mutant astrocytoma harboring SNVs of PIK3CA and PIK3R1 showed a significantly worse overall survival (OS) than wild-type patients. AEBP1 amplification was associated with shorter OS in GBM. Our study suggests that clinical sequencing can recapitulate previous findings, which may provide a powerful approach to discover diagnostic, therapeutic and prognostic markers for precision medicine in adult-type diffuse gliomas.

Mono(ADP-ribosyl)ation (MARylation), a post-translational modification (PTM) of proteins, is emerging as a critical regulator of ribosome function and translation. Herein, we demonstrate that RACK1, a member of the tryptophan-aspartate repeat (WD-repeat) family of proteins and an integral component of the ribosome, is MARylated by the mono(ADP-ribosyl) transferase (MART) PARP14 in ovarian cancer cells. We mapped and confirmed the sites of MARylation, which occur on three acidic residues within blades 4 and 5 of β-propeller domain of RACK1, a chaperone that shuttles and anchors proteins where needed. Site-specific MARylation of RACK1 is required for stress granule formation and promotes the colocalization of RACK1 to stress granules with key components, such as G3BP1, eIF3η, and 40S ribosomal proteins. In parallel, we observed reduced translation of a subset of mRNAs, including those encoding key cancer regulators (e.g., AKT). Treatment with a PARP14 inhibitor or mutation of the sites of MARylation on RACK1 blocks these outcomes. To re-set the system after prolonged stress and recovery, the ADP-ribosyl hydrolase TARG1 deMARylates RACK1 to dissociate the stress granules and return RACK1 and the 40S ribosomal subunit to the cytoplasm, allowing for a restoration of translation. Collectively, our results highlight the discovery of a PARP14/TARG1-regulated RACK1 MARylation cycle that controls stress granule assembly and disassembly in ovarian cancer cells.

AIMS:H3K27M-mutant diffuse midline glioma (DMG) is a rare and aggressive central nervous system tumor. The biological behavior, clinicopathological characteristics, and prognostic factors of DMG have not yet been completely uncovered, especially in adult patients. This study aims to investigate the clinicopathological characteristics and identify prognostic factors of H3K27M-mutant DMG in pediatric and adult patients, respectively.METHODS:A total of 171 patients with H3K27M-mutant DMG were included in the study. The clinicopathological characteristics of the patients were analyzed and stratified based on age. The Cox proportional hazard model was used to determine the independent prognostic factors in pediatric and adult subgroups.RESULTS:The median overall survival (OS) for the entire cohort was 9.0 months. Significant differences were found in some clinicopathological characteristics between children and adults. The median OS was also significantly different between the pediatric and adult subgroups, with 7.1 months for children and 12.3 months for adults (p < 0.001). In the overall population, the multivariate analysis identified adult patients, single lesion, concurrent chemoradiotherapy/radiotherapy, and intact ATRX expression as independent favorable prognostic factors. In the age-stratified subgroups, the prognostic factors varied between children and adults, with intact ATRX expression and single lesion being independent favorable prognostic factors in adults, while infratentorial localization was significantly associated with worse prognosis in children.CONCLUSIONS:The differences in clinicopathological features and prognostic factors between pediatric and adult patients with H3K27M-mutant DMG suggest the need for further clinical and molecular stratification based on age.

Gene regulation in the nucleus requires precise control of the molecular processes that dictate how, when, and which genes are transcribed. The posttranslational modification (PTM) of histones in chromatin is an effective means to link cellular signaling to gene expression outcomes. The repertoire of histone PTMs includes phosphorylation, acetylation, methylation, ubiquitylation, and ADP-ribosylation (ADPRylation). ADPRylation is a reversible PTM that results in the covalent transfer of ADP-ribose units derived from NAD+ to substrate proteins on glutamate, aspartate, serine, and other amino acids. Histones were the first substrate proteins identified for ADPRylation, over five decades ago. Since that time, histone ADPRylation has been shown to be a widespread and critical regulator of chromatin structure and function during transcription, DNA repair, and replication. Here, we describe a set of protocols that allow the user to investigate site-specific histone ADPRylation and its functional consequences in biochemical assays and in cells in a variety of biological systems. With the recent discovery that some cancer-causing histone mutations (i.e., oncohistone mutations) occur at functional sites of regulatory ADPRylation, these protocols may have additional utility in studies of oncology.

ObjectiveTumor-treating fields (TTFields) are a new therapeutic modality for patients with glioblastoma (GBM). However, studies on survival outcomes of TTFields are rarely reported in China. This study aimed to examine the clinical efficacy and safety of TTFields therapy for GBM in China.MethodsA total of 93 patients with newly diagnosed GBM (ndGBM) and recurrent GBM (rGBM) were included in our study retrospectively. They were divided into two groups based on whether they used TTFields. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed.ResultsAmong the patients with ndGBM, there were 13 cases with TTFields and 39 cases with no TTFields. The median PFS was 15.3 [95% confidence interval (CI): 6.5–24.1] months and 10.6 (95% CI: 5.4–15.8) months in the two groups, respectively, with P = 0.041. The median OS was 24.8 (95% CI: 6.8–42.8) months and 18.6 (95% CI: 11.4–25.8) months, respectively, with P = 0.368. Patients with subtotal resection (STR) who used TTFields had a better PFS than those who did not (P = 0.003). Among the patients with rGBM, there were 13 cases with TTFields and 28 cases with no TTFields. The median PFS in the two groups was 8.4 (95% CI: 1.7–15.2) months and 8.0 (95% CI: 5.8–10.2) months in the two groups, respectively, with P = 0.265. The median OS was 10.6 (95% CI: 4.8–16.4) months and 13.3 (95% CI: 11.0–15.6) months, respectively, with P = 0.655. A total of 21 patients (21/26, 80.8%) with TTFields developed dermatological adverse events (dAEs). All the dAEs could be resolved or controlled.ConclusionTTFields therapy is a safe and effective treatment for ndGBM, especially in patients with STR. However, it may not improve survival in patients with rGBM.

Postoperative cerebral ischemic complication is the most common complication of revascularization surgery for patients with moyamoya disease (MMD). This retrospective study was conducted on 63 patients with ischemic MMD. Postoperative ischemia occurred in 15 of the 70 revascularization operations performed for patients after surgical revascularization, translating to an incidence of 21.4%. Univariate analysis revealed that onset infarction ( p = 0.015), posterior cerebral artery involvement ( p = 0.039), strict perioperative management ( p = 0.001), interval time between transient ischemic attack (TIA) or infarction presentation and operation ( p = 0.002) and preoperatively cerebral infarction extent score (CIES) ( p = 0.002) were significantly associated with postoperative cerebral ischemia. Multivariate analysis revealed that strict perioperative management (OR = 0.163; p = 0.047), and preoperatively CIES (OR = 1.505; p = 0.006) were independently associated with postoperative cerebral ischemia-related complications. After comprehensive improvement of perioperative management protocol, the incidence of symptomatic infarction declined to 7.4% (4 out of 54). Analysis of the area under the receiver operating characteristic curve (AUROC) indicated CIES was a predictor for both postoperative ischemia and high follow-up modified Rankin Scale scores. In summary, strict perioperative management and CIES were identified as independent risk factors for postoperative ischemic complications in ischemic MMD, demonstrating that comprehensive and individualized perioperative management improve postoperative outcomes in patients with MMD. Furthermore, application of CIES to evaluate pre-existing cerebral infarction can improve the management of patients.

H3K27M mutated diffuse midline gliomas (DMGs) are extremely aggressive and the leading cause of cancer‐related deaths in pediatric brain tumors with 5‐year survival <1%. Radiotherapy is the only established adjuvant treatment of H3K27M DMGs; however, the radio‐resistance is commonly observed.

Background: Glioblastoma (GBM) has a poor prognosis, and patients with epidermal growth factor receptor (EGFR) amplification have an even worse prognosis. Nimotuzumab is an EGFR monoclonal antibody thought to play a significant role in the treatment of GBM. This paper presents a retrospective cohort study that evaluates the clinical efficacy and safety of nimotuzumab in GBM. Materials and Methods: A total of 56 newly diagnosed patients with EGFR-positive GBM were included in our study. The patients were divided into radiotherapy (RT) + temozolomide (TMZ) + nimotuzumab (39 patients) and RT + TMZ (17 patients) groups based on whether or not nimotuzumab was added during RT. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed. Results: The median follow-up time was 27.9 months (95% confidence interval [CI], 25.1-30.8). The median PFS was 12.4 months (95% CI, 7.8-17.0) and 8.2 months (95% CI, 6.1-10.3) in the 2 groups, respectively, P = .052. The median OS was 27.3 months (95% CI, 19.0-35.6) and 16.7 months (95% CI, 11.1-22.2), respectively, P = .018. In patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter, the PFS and OS were significantly better in patients treated with nimotuzumab than in those without nimotuzumab (median PFS: 19.3 vs 6.7 months, P = .001; median OS: 20.2 vs 13.8 months, P = .026). During the treatment period, no statistically significant difference in toxicity was noted between the 2 groups. Conclusion: Our retrospective cohort study suggests the efficacy of Nimotuzumab combined with concurrent RT with TMZ in patients with newly diagnosed EGFR-positive GBM, and specifically those with unmethylated MGMT promoter. Further prospective studies are warranted to validate our findings. Besides, nimotuzumab demonstrated good safety and tolerability.

Supplementary Data from Oncohistone Mutations Occur at Functional Sites of Regulatory ADP-Ribosylation

Objective To evaluate the long-term outcomes and safety of endoscopic transsphenoidal surgery (ETS) in recurrent and residual pituitary adenomas (rrPAs), as well as the predictors of gross total resection (GTR) and intraoperative CSF leakage. Furthermore, to compare outcomes and complications with non-rrPAs cohort. Methods Clinical and radiological characteristics of patients with rrPAs who underwent ETS were collected between 2017 and 2020. Data of patients with non-rrPAs were collected from 2019 to 2020. Logistic regression analyses were performed to investigate the factors influencing gross total resection (GTR) and intraoperative CSF leakage. Between-group comparisons of outcomes and complications were performed through propensity score analysis. Results We enrolled 73 patients with rrPAs. GTR was achieved in 41 (56.1%) cases; further, GTR or near-total resection was achieved in 93.2% of patients. The mean tumor volumes for GTR and non-GTR cases were 6.2 ±7.2 cm3 and 11.1 ±9.1 cm3, respectively. Multivariate regression analysis of the GTR rate in patients with rrPAs revealed that Knosp grade was an independent factor (odds ratio [OR] = 0.324; p=0.005). Moreover, previous transcranial surgery and non-functional pituitary adenomas were risk factors for intraoperative CSF leakage in patients with rrPAs (OR=6.450, p=0.019 and OR=7.472, p=0.012, respectively). After propensity score matching, There was no significant difference in the GTR rate between patients with rrPAs and patients with non-rrPAs. Contrastingly, patients with rrPAs had a higher rate of intraoperative CSF leakage and longer postoperative hospital stay than patients with non-rrPAs. During the follow-up, vision improved in 9 (22.0%) and 24 (62.5%) patients with rrPAs and non-rrPAs, respectively. Although there was a trend that reoperation of rrPAs involved a lower hypopituitarism recovery rate and biochemical remission rate, as well as a higher hypopituitarism rate, there was no statistically significant between-group difference. Conclusions Knosp grade was an independent factor for GTR in endoscopic transsphenoidal surgery in patients with rrPAs. Previous transcranial surgery and non-functional PAs were risk factors for intraoperative CSF leakage. Although associated with longer hospital stay, rrPAs did not associate with lower GTR rate or more frequent postoperative complications than non-rrPAs cohort.

Electroporation is the process of instantaneously increasing the permeability of a cell membrane under a pulsed electric field. Depending on the parameters of the electric pulses and the target cell electrophysiological characteristics, electroporation can be either reversible or irreversible. Reversible electroporation facilitates the delivery of functional genetic materials or drugs to target cells, inducing cell death by apoptosis, mitotic catastrophe, or pseudoapoptosis; irreversible electroporation is an ablative technology which directly ablates a large amount of tissue without causing harmful thermal effects; electrotherapy using an electric field can induce cell apoptosis without any aggressive invasion. Reversible and irreversible electroporation can also activate systemic antitumor immune response and enhance the efficacy of immunotherapy. In this review, we discuss recent progress related to electroporation, and summarize its latest applications. Further, we discuss the synergistic effects of electroporation-related therapies and immunotherapy. We also propose perspectives for further investigating electroporation and immunotherapy in cancer treatment.

Epilepsy treatments for patients with mechanistic target of rapamycin (mTOR) disorders, such as tuberous sclerosis complex (TSC) or focal cortical dysplasia type II (FCDII), are urgently needed. In these patients, the presence of focal cortical malformations is associated with the occurrence of lifelong epilepsy, leading to severe neurological comorbidities. Here, we show that the expression of the actin cross-linking protein filamin A (FLNA) is increased in resected cortical tissue that is responsible for seizures in patients with FCDII and in mice modeling TSC and FCDII with mutations in phosphoinositide 3-kinase (PI3K)-ras homolog enriched in brain (Rheb) pathway genes. Normalizing FLNA expression in these mice through genetic knockdown limited cell misplacement and neuronal dysmorphogenesis, two hallmarks of focal cortical malformations. In addition, Flna knockdown reduced seizure frequency independently of mTOR signaling. Treating mice with a small molecule targeting FLNA, PTI-125, before the onset of seizures alleviated neuronal abnormalities and reduced seizure frequency compared to vehicle-treated mice. In addition, the treatment was also effective when injected after seizure onset in juvenile and adult mice. These data suggest that targeting FLNA with either short hairpin RNAs or the small molecule PTI-125 might be effective in reducing seizures in patients with TSC and FCDII bearing mutations in PI3K-Rheb pathway genes.

Background: Although the diagnosis and treatment of glioblastoma (GBM) is significantly improved with recent progresses, there is still a large heterogeneity in therapeutic effects and overall survival. The aim of this study is to analyze gene expressions of transcription factors (TFs) in GBM so as to discover new tumor markers. Methods: Differentially expressed TFs are identified by data mining using public databases. The GBM transcriptome profile is downloaded from The Cancer Genome Atlas (TCGA). The nonnegative matrix factorization (NMF) method is used to cluster the differentially expressed genes to discover hub genes and signal pathways. The TFs affecting the prognosis of GBM are screened by univariate and multivariate COX regression analysis, and the receiver operating characteristic (ROC) curve is determined. The GBM hazard model and nomogram map are constructed by integrating the clinical data. Finally, the TFs involving potential signaling pathways in GBM are screened by Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results: There are 68 differentially expressed TFs in GBM, of which 43 genes are upregulated and 25 genes are downregulated. NMF clustering analysis suggested that GBM patients are divided into three groups: Clusters A, B, and C. LHX2, MEOX2, SNAI2, and ZNF22 are identified from the above differential genes by univariate/multivariate regression analysis. The risk score of those four genes are calculated based on the beta coefficient of each gene, and we found that the predictive ability of the risk score gradually increased with the prolonged predicted termination time by time-dependent ROC curve analysis. The nomogram results have showed that the integration of risk score, age, gender, chemotherapy, radiotherapy, and 1p/19q can further improve predictive ability towards the survival of GBM. The pathways in cancer, phosphoinositide 3-kinases (PI3K)-Akt signaling, Hippo signaling, and proteoglycans, are highly enriched in high-risk groups by GSEA. These genes are mainly involved in cell migration, cell adhesion, epithelial-mesenchymal transition (EMT), cell cycle, and other signaling pathways by GO and KEGG analysis. Conclusion: The four-factor combined scoring model of LHX2, MEOX2, SNAI2, and ZNF22 can precisely predict the prognosis of patients with GBM.

Tremendous efforts have been made to explore biomarkers for classification and grading on gliomas. The goal of this study was to identify more molecular features that are associated with clinical outcomes by comparing the genomic profiles of primary and recurrent gliomas and determine potential recurrence leading factors that are significantly enriched in relapse tumors. Hybrid capture based next generation sequencing (NGS) analysis was performed on 64 primary and 17 recurrent glioma biopsies. Copy number variation (CNV) was more frequent in recurrent tumors and CDKN2A/B loss was significantly enriched. In addition, overall mutations in cell cycle pathway are more common in relapse tumors. The patterns of gene sets, including IDH1/TERT and IDH1/TP53 exhibited significant difference between the groups. Survival analysis uncovered the worse disease-free survival (DFS) and overall survival (OS) associated with altered copy number and excessive activation of CELL CYCLE pathway. High Tumor Mutation Burden (TMB) was also a biomarker with great potential for poor prognosis. The assessment of genomic characteristics in primary versus recurrent gliomas aids the discovery of potential predictive biomarkers. The prognostic value of TMB in gliomas was raised for the first time.

Aim: To identify spinocerebellar ataxia Type 3 (SCA3)-related exosomal biomarkers and the underlying mechanisms. Materials & methods: Exosomal RNAs from plasma and cerebrospinal fluid (CSF) were extracted from 24 SCA3 patients and 22 controls, respectively. Small RNA sequencing and quantitative PCR verification were performed. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the results were carried out. Results: One novel miRNA is notably downregulated in plasma-derived exosomes, while upregulated in CSF-derived exosomes of SCA3 patients. Besides, it is successively upregulated in CSF-derived exosomes from Type 1, Type 2 and Type 3 groups. The downstream target genes were enriched in protein processing in endoplasmic reticulum and axon guidance. Conclusion: One exosomal biomarker was identified in SCA3, and this is the first time to report an exosomal miRNA as a biomarker in SCA3 internationally.

We combined translating ribosome affinity purification (TRAP) with in utero electroporation (IUE), called iTRAP to identify the molecular profile of specific neuronal populations during neonatal development without the need for viral approaches and FACS sorting. We electroporated a plasmid encoding EGFP-tagged ribosomal protein L10a at embryonic day (E) 14-15 to target layer 2-4 cortical neurons of the somatosensory cortex. At three postnatal (P) ages-P0, P7, and P14-when morphogenesis occurs and synapses are forming, TRAP and molecular profiling was performed from electroporated regions. We found that ribosome bound (Ribo)-mRNAs from ∼7300 genes were significantly altered over time and included classical neuronal genes known to decrease (e.g., Tbr1, Dcx) or increase (e.g., Eno2, Camk2a, Syn1) as neurons mature. This approach led to the identification of specific developmental patterns for Ribo-mRNAs not previously reported to be developmentally regulated in neurons, providing rationale for future examination of their role in selective biological processes. These include upregulation of Lynx1, Nrn1, Cntnap1 over time; downregulation of St8sia2 and Draxin; and bidirectional changes to Fkbp1b. iTRAP is a versatile approach that allows researchers to easily assess the molecular profile of specific neuronal populations in selective brain regions under various conditions, including overexpression and knockdown of target genes, and in disease settings.

Objective To investigate the role of neuroglobin (NGB) and vascular endothelial growth factor (VEGF) regulated by hypoxia-inducible factor-1 (HIF-1) in promoting angiogenesis after cerebral contusion and laceration.Methods Proteomic technology was used to compare differentially expressed proteins in the frontal lobe between patients with cerebral contusion and laceration and those with non-traumatic brain injury,and bioinformatics technology was used for the analysis and identification of differentially expressed proteins.Immunohistochemistry and ELISA were used to measure the expression of HIF-1,NGB,and VEGF in cerebral tissue and serum.Results The 2-dimensional gel electrophoresis profile was established for brain tissues from patients with cerebral contu sion and laceration or non-traumatic brain injury,and 7 differentially expressed proteins were identified,including HIF-1,NGB,and VEGF.Immunohistochemistry showed that the patients with cerebral contusion and laceration had higher expression of HIF-1,NGB,and VEGF in brain tissue than those with non-traumatic brain injury.The results of ELISA showed that the patients with cerebral contu sion and laceration had higher expression of HIF-1,NGB,and VEGF in serum than those with non-traumatic brain injury.Conclusions HIF-1 regulates the release of two target genes NGB and VEGF after cerebral contusion and laceration and thus plays an important role in cerebral angiogenesis.Changes in the serum levels of HIF-1,NGB,and VEGF can be used as a reference for clinical evaluation and monitoring of the severity of hypoxic-ischemic encephalopathy.They also have important significance in the diagnosis,treatment,and outcome of cerebral contusion and laceration and await in-depth research.

BACKGROUND: Choroid plexus papillomas (CPPs) are rare benign tumors, and the pigmented subtype is observed even more rarely. CASE DESCRIPTION: We present the case of a 43-year-old woman with complaints of headache and progressive left monocular visual deterioration, whose initial plain computed tomography CT scan showed an ovate high-density tumor located within the insellar region. Magnetic resonance imaging revealed a homogeneously contrast-enhancing tumor extending from the sella turcica to the suprasellar cistern. Single-nostril transsphenoidal endoscopic resection followed by subfrontal subtotal resection was performed in this patient. Postoperative histology revealed that the tumor consisted of hyperchromatic tissue with papillary features. Higher-resolution examination of the tissue revealed this tissue was composed of hyperplastic columnar epithelial cells with hyperchromatic cytoplasmic pigment. Subsequent immunohistochemistry identified the lesion as a pigmented choroid plexus papilloma. Here we review the current literature, discuss the origin of the tumor, the differential diagnosis, and the roles of surgery and radiotherapy. CONCLUSIONS: This case study provides important clinical information for the evaluation, diagnosis, and treatment of pigmented CPP in the sellar region.