OBJECTIVE:The occurrence and predictors of symptomatic subdural hygroma (SSH) subsequent to the fenestration of pediatric intracranial arachnoid cysts (IACs) are unclear. In this study, the authors aimed to investigate the likelihood of an SSH following IAC fenestration and the impact on operative efficacy with the ultimate goal of constructing a nomogram. METHODS:The medical records of 1782 consecutive patients who underwent surgical treatment at the Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were reviewed. Among these patients, a training cohort (n = 1214) underwent surgery during an earlier period and was used for the development of a nomogram. The remaining patients formed the validation cohort (n = 568) and were used to confirm the performance of the developed model. The development of the nomogram involved the use of potential predictors, while internal validation was conducted using a bootstrap-resampling approach. RESULTS:SSH was detected in 13.2% (160 of 1214) of patients in the training cohort and in 11.1% (63 of 568) of patients in the validation cohort. Through multivariate analysis, several factors including Galassi type, IAC distance to the basal cisterns, temporal bulge, midline shift, IAC shape in the coronal view, area of the stoma, and artery location near the stoma were identified as independent predictors of SSH. These 7 predictors were used to construct a nomogram, which exhibited a concordance statistic (C-statistic) of 0.826 and demonstrated good calibration. Following internal validation, the nomogram maintained good calibration and discrimination with a C-statistic of 0.799 (95% CI 0.665-0.841). Patients who had nomogram scores < 30 or ≥ 30 were considered to be at low and high risk of SSH occurrence, respectively. CONCLUSIONS:The predictive model and derived nomogram achieved satisfactory preoperative prediction of SSH. Using this nomogram, the risk for an individual patient can be estimated, and the appropriate surgery can be performed in high-risk patients.

Background Medulloblastoma (MB) is a malignant pediatric central nervous system tumor that is prone to leptomeningeal metastasis. Currently, apart from magnetic resonance imaging and cerebrospinal fluid (CSF) cytology, there are no reliable biomarkers for MB progression. Cytokines are key proteins in signaling pathways in the tumor microenvironment and are closely related to tumor recurrence and progression. This study aimed to investigate the CSF cytokine profile in pediatric patients with MB to identify biomarkers of tumor progression and metastasis. Methods In total, 10 patients were recruited for this study. Five patients had nonmetastatic MB and five had metastatic MB. A cytokine antibody array was used to detect the expression of 120 cytokines in the CSF, and differentially expressed cytokines were screened by integrated bioinformatics analysis. Results Twenty-seven cytokines were upregulated in patients with MB compared to control individuals. Of these, eight were upregulated by >1.5-fold (CCL2, BMP-4, beta-NGF, FGF-7, IL-12p40, eotaxin-2, M-CSF, and NT-4). Twelve cytokines were differentially expressed between patients with metastatic MB and nonmetastatic (nine cytokines were upregulated and three were downregulated). Among them, NAP-2, MIP-1α, MIP-1β, IGFBP-1, IGFBP-2 and IGFBP-3 were upregulated by more than two-fold. Gene Ontology analysis revealed that the upregulated cytokines were enriched mainly in “epithelial cell proliferation” and “chemotaxis,” and the Kyoto Encyclopedia of Genes and Genomes analysis indicated the enrichment of the “MAPK,” “PI3K-Akt,” and “Ras” signaling pathways. Conclusions The present study investigated cytokine profiles in the CSF of pediatric patients with MB. Our results suggest that these differentially expressed cytokines may serve as novel markers for detecting MB, especially for assessing the risk of progression and metastasis.

Medulloblastoma (MB) is a prevalent malignant brain tumor among children, which can be classified into four primary molecular subgroups. Group 3 MB (G3-MB) is known to be highly aggressive and associated with a poor prognosis, necessitating the development of novel and effective therapeutic interventions. Ferroptosis, a regulated form of cell death induced by lipid peroxidation, has been identified as a natural tumor suppression mechanism in various cancers. Nevertheless, the potential role of ferroptosis in the treatment of G3-MB remains unexplored. In this study, we demonstrate that RNF126 acts as an anti-ferroptotic gene by interacting with ferroptosis suppressor protein 1 (FSP1, also known as AIFM2) and ubiquitinating FSP1 at the 4KR-2 sites. Additionally, the deletion of RNF126 reduces the subcellular localization of FSP1 in the plasma membrane, resulting in an increase in the CoQ/CoQH2 ratio in G3-MB. The RNF126-FSP1-CoQ10 pathway plays a pivotal role in suppressing phospholipid peroxidation and ferroptosis both in vivo and in vitro. Clinically, RNF126 exhibited elevated expression in G3-MB and its overexpression was significantly associated with reduced patient survival. Our findings indicate that RNF126 regulates G3-MB sensitivity to ferroptosis by ubiquitinating FSP1, which provides new evidence for the potential G3-MB therapy.

BackgroundThe significant progress of immune therapy in non-central nervous system tumors has sparked interest in employing the same strategy for adult brain tumors. However, the advancement of immunotherapy in pediatric central nervous system (CNS) tumors is not yet on par. Currently, there is a lack of comprehensive comparative studies investigating the immune ecosystem in pediatric and adult CNS tumors at a high-resolution single-cell level.MethodsIn this study, we comprehensively analyzed over 0.3 million cells from 171 samples, encompassing adult gliomas (IDH wild type and IDH mutation) as well as four major types of pediatric brain tumors (medulloblastoma (MB), ependymoma (EPN), H3K27M-mutation (DIPG), and pediatric IDH-mutation glioma (P-IDH-M)). Our approach involved integrating publicly available and newly generated single-cell datasets. We compared the immune landscapes in different brain tumors, as well as the detailed functional phenotypes of T-cell and myeloid subpopulations. Through single-cell analysis, we identified gene sets associated with major cell types in the tumor microenvironment (gene features from single-cell data, scFes) and compared them with existing gene sets such as GSEA and xCell. The CBTTC and external GEO cohort was used to analyze and validate the immune-stromal-tumor patterns in pediatric brain tumors which might potentially respond to the immunotherapy.ResultsFrom the perspective of single-cell analysis, it was observed that major pediatric brain tumors (MB, EPN, P-IDH-M, DIPG) exhibited lower immune contents compared with adult gliomas. Additionally, these pediatric brain tumors displayed diverse immunophenotypes, particularly in regard to myeloid cells. Notably, the presence of HLA-enriched myeloid cells in MB was found to be independently associated with prognosis. Moreover, the scFes, when compared with commonly used gene features, demonstrated superior performance in independent single-cell datasets across various tumor types. Furthermore, our study revealed the existence of heterogeneous immune ecosystems at the bulk-RNA sequencing level among different brain tumor types. In addition, we identified several immune-stromal-tumor patterns that could potentially exhibit significant responses to conventional immune checkpoint inhibitors.ConclusionThe single-cell technique provides a rational path to deeply understand the unique immune ecosystem of pediatric brain tumors. In spite of the traditional attitudes of “cold” tumor towards pediatric brain tumor, the immune-stroma-tumor patterns identified in this study suggest the feasibility of immune checkpoint inhibitors and pave the way for the upcoming tide of immunotherapy in pediatric brain tumors.

ObjectivesTo investigate the potential factors affecting the clinical prognosis of intracranial sylvian arachnoid cysts(IAC) in children.MethodsAll patients with IAC admitted to our department from January, 1, 2015 to December, 31, 2016, were retrospectively reviewed. Patients were grouped based on surgical treatment (surgery cohort vs non-surgery cohort). The clinical and image outcome of the patients were followed routinely. The clinical characteristics and the prognosis of the patients were compared in different cohorts. Binary logistic regression analysis was applied to analyze the potential factors which may post an influence on the prognosis of the patients.ResultsOf 500 patients admitted to our department for IAC, 424 patients had good prognosis and 76 had poor prognosis, with no deaths occurred during the follow-ups. 68 patients had IAC related complications and 91 patients developed new symptoms during the follow-ups. There were significant differences (P < 0.05) between the 2 cohorts in below aspects: age, gender, Galassi subtype, whether the mother was a unipara, the maximum diameter of the cysts at the first visit and the last follow-up, headache, head circumference, temporal bulge, new symptoms, cysts rupture and hemorrhage, subdural effusion, and IAC disappearance. The mean changes in the maximum diameter of the IAC for the patients were marginally higher for the surgery cohort than for the non-surgery cohort (P < 0.01). Binary logistic regression analysis suggested that the number of symptom, no new symptoms during follow-up, surgical treatment, age, maximum diameter of cysts at first diagnosis were independent risk factors affecting the prognosis of patients (P < 0.05).ConclusionsPatients older than 22.5 months, with the maximum diameter of IAC greater than 5.75 cm, who have multiple symptoms, born prematurely, develope new symptoms during the follow-ups and obvious symptoms after trauma need to conduct necessary surgical treatment in time. Patients with complications such as cysts rupture with hemorrhage and subdural effusion will acquire good prognosis after timely surgical treatment. IAC complete disappearance warrants no such important attention for the good prognosis.

Background:Children are more susceptible to the higher rate of massive blood transfusion because of the less allowable blood loss and lower intraoperative tolerance to blood loss during the resection of brain tumors. The surgical concept of en bloc resection, which is widely used in other tumors, may contribute to the improvement of brain tumor resection. However, there is still a lack of comprehensive research on its application in pediatric brain tumors.Objective:The aim of this study is to investigate the outcomes of the en bloc concept and the factors associated with the application of the en bloc concept in pediatric brain tumors.Methods:According to the surgical concept involved, the patients were divided into three subgroups: complete en bloc concept, partial en bloc concept, and piecemeal concept. The matching comparison (complete and partial en bloc concept groups vs. piecemeal concept group) was conducted to investigate the effect of the en bloc concept on the outcomes. Then, the patient data from January 2018, when the en bloc concept was routinely integrated into the brain tumor surgery in our medical center, were reviewed and analyzed to find out the predictors associated with the application of en bloc concept.Results:In the en bloc group, the perioperative parameters, such as hospital stay (p = 0.001), pediatric intensive care unit (PICU) stay (p = 0.003), total blood loss (p = 0.015), transfusion rate (p = 0.005), and complication rate (p = 0.039), were all significantly improved. The multinomial logistic regression analysis showed that tumor volume, bottom vessel, and imaging features, such as encasing nerve or pass-by vessel, finger-like attachment, ratio of "limited line", and ratio of "clear line", were independent predictors for the application of the en bloc concept in our medical center.Conclusion:This study supports the application of complete and partial en bloc concept in the pediatric brain tumor surgery based on the preoperative evaluation of imaging features, and compared with the piecemeal concept, the en bloc concept can improve the short outcomes without significant increases in the neurological complications. Large-series and additional supportive pieces of evidence are still warranted.

The aim of this study is to investigate the clinical characteristics and prognostic effects of different subtypes of suprasellar arachnoid cysts (SAC) in children. Fifty patients with primary SAC who had undergone endoscopic treatment in our department between January 2010 and December 2020 were studied retrospectively. All patients underwent endoscopic treatment after diagnosis, including ventriculocystostomy (VC) in 23 cases and ventriculocystocisternostomy (VCC) in 27 cases. All patients were followed up regularly after the operation, including head computed tomography (CT)/magnetic resonance imaging (MRI), and Evans index (EI) and frontal and occipital horn ratio (FOHR) index were measured to assess changes in cyst volume and hydrocephalus. The prognosis was evaluated comprehensively on the data of the improvement of clinical symptoms, child growth and development correlation score, and reduction of cyst volume 12 months after surgery. According to the new classification of SAC, 50 cases of children were classified into three groups in which we compared the clinical characteristics of different subtypes of the three groups. Logistic regression was used to analyze the influencing factors of prognosis. Completed success was achieved in 50 cases, including 31 cases with cyst volume reduction of more than 50

Lateral ventricle meningiomas (LVM) in children are very rare. The current research is mostly limited to adults, and there are very few related studies on children. The purpose of this study was to analyze the clinicopathological and imaging features of lateral ventricle meningiomas in children. A retrospective analysis of five children with pathologically confirmed lateral ventricle meningioma was performed, and we collected clinical data, including clinicopathological data, treatment prognosis data, and imaging features (including tumor location, signal intensity, enhancement degree, intratumoral cyst, calcification, peritumoral edema, and associated hydrocephalus). Among the 5 patients with LVM, 4 were male and 1 was female with an average age of 7.6 years (range 2 to 12 years). All CT scans showed slight hyperintensity or isodensity, and only 1 patient had calcification. Two patients demonstrated cyst changes. Four patients had varying degrees of peritumoral edema. The average tumor volume was 164.1 cm3 (1.4–314.9 cm3). All 5 patients with LVM were iso- or hypointense on T1WI. The T2WI signals had no obvious features. Four patients had a high signal on DWI (80

Abstract OBJECTIVE: Medulloblastoma (MB) is a malignant embryonal tumor that develops especially in childhood, with overall survival (OS) at 5 years of up to 70%. The aim of the study is to explore the clinical profile and outcome among the histo-molecular subgroups in Chinese children. METHODS: A total of 93 patients of MB who underwent surgical treatment at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2006 to December 2015. The clinical profile, treatment, and survival patterns are discussed. The relevant statistical analysis was done using SPSS software, version 21.0. RESULTS: At the most recent follow-up date, 15 (16.1%) had been lost to follow-up，78 cases were tested for RNA-seq, of which 54 cases were successful, and 24 cases failed the quality control due to sample quality problems.The male-to-female ratio was 2.4:1, and the patients’ mean age at diagnosis was 5 years (ranged from 4 months to 11 years).The estimated 5-year overall survival and progression-free survival, based on Kaplan-Meier analysis, were 55.1% ± 5.6% and 40.9% ± 5.7%.Multivariate survival analysis showed that progression -free survival were significantly affected by extent of surgery (P=0.026) and postoperative radiotherapy(P＜0.001).Preoperative metastasis (P=0.032) and postoperative radiotherapy (P=0.001) had a significant influence on overall survival. While，the molecular subtypes showed no statistically significant differences in 5-year PFS and 5-year OS. CONCLUSION: Extent of resection of MB and postoperative radiotherapy were the important clinical prognostic factors for survival. In the future, we will continue to expand cases and study the clinical characteristics and prognostic risk factors of different molecular types of medulloblastoma in Chinese children,and to improve the survival rate of children with medulloblastoma.

Abstract BACKGROUND: The less allowable blood loss and tolerance of intraoperative blood loss of children lead to the high rate of massive blood transfusion. The surgical concepts of en bloc resection may contribute to the improvement of brain tumor resection. OBJECTIVE: To investigate the effects of en bloc concept on short outcomes of pediatric brain tumors and factors associated with the application of en bloc concept. METHODS: According to the surgical concept involved, the patients were divided into three subgroups-complete en bloc concept, partial en bloc concept and piecemeal concept. The matching-comparison(en bloc group consisting of the first two subgroups and piecemeal group) was conducted to investigate the effect of the en bloc concept on the short-term outcomes. Then the patient data after January 2018, when the en bloc concept was routinely integrated into brain tumor surgery in our medical center, were reviewed and analyzed to find out the predictors associated with the application of en bloc concept. RESULTS: In the en bloc group, the perioperative outcomes, including hospital stay(p=0.001), PICU stay(p=0.003), total blood loss(p=0.015), transfusion rate(p=0.005) and complication rate(p=0.039), were all significantly improved. The multinomial logistic regression analysis showed that tumor volume, bottom vessel, and imaging features, like encasing nerve or pass-by vessel, finger-like attachment, ratio of “limited line” and ratio of “clear line” remained independent predictors for the application of en bloc concept in our medical center. CONCLUSION: The application of en bloc concept based on the imaging features can improve the short-term outcomes.

Minichromosome maintenance proteins are DNA-dependent ATPases that bind to replication origins and allow a single round of DNA replication. One member of this family, MCM3, is reportedly active in most cancers. To systematically elucidate the mechanisms affected by aberrant MCM3 expression and evaluate its clinical significance, we analyzed multi-omics data from the GEO database and validated them in cell lines and tumor samples. First, we showed the upregulation of MCM3 in medulloblastoma (MB) at bulk and single-cell RNA sequence levels and revealed the potential role of MCM3 via DNA replication. Then we found the dysregulation of MCM3 might result from abnormal methylation of MCM3. Moreover, we discovered that MCM3 might affect varied biological processes such as apoptosis, autophagy, and ferroptosis and that MCM3 was correlated with immune components such as fibroblast and neutrophils, which were associated with overall survival in different medulloblastoma subtypes. Furthermore, we found that MCM3 expression was correlated with the IC50 values of cisplatin and etoposide. The nomogram of MCM3-related genes showed the reliable and better prediction of 1- and 5-year survival compared to current histological and molecular classifications. Overall, the results of our study demonstrated that MCM3 might serve as a potential biomarker with clinical significance and better guidance than current histological and molecular classifications for clinical decision-making.

[This corrects the article DOI: 10.3389/fmolb.2022.815260.].

Objective:To evaluate the clinical efficacy of botulinum toxin injection for pediatric neurogenic detrusor overactivity.Methods:From April 2020 to June 2021, a retrospective observational self-control study was performed for neurogenic detrusor overactive children receiving an injection of botulinum toxin at Department of Pediatric Urological Surgery of Children's Hospital of Fudan University.All cases received continuous antibiotic prophylaxis with limited effect.Febrile urinary tract infection, maximal voiding volume at Month 1/3/6 post-injection, bladder wall thickness on ultrasound, maximal bladder capacity, safe bladder capacity and bladder urodynamic compliance at Month 3 post-injection were compared before and after injection.Results:There were 1 boy and 10 girls with a mean age of (80.36±43.35) months and a mean weight of (21.86±7.47) kg.Prior to injection, mean clean intermittent catheterization frequency was (5.86±1.60) times per day, maximal bladder capacity (152.73±58.10) mL, rate of febrile urinary tract infection 100% and bladder wall thickness (4.41±1.95) mm.In pre-injection urodynamic tests, maximal bladder capacity was (158.44±57.26) mL, safe bladder capacity (139.78±66.09) mL and bladder compliance (4.37±2.16) mL/cmH 2O.After injection, mean clean intermittent catheterization frequency at Month 1 was (6.18±2.31) times per day ( P=0.652), Month 3 (5.91±2.38) times per day ( P=0.948), Month 6 (5.68±1.91) times per day ( P=0.736), maximal voiding volume at Month 1 (206.82±72.05) mL ( P=0.004), Month 3 (227.28±94.67) mL ( P=0.003) and Month 6 (227.28±94.67) mL ( P=0.024). Febrile urinary tract infection rate at Month 1 was 1(9%)( P<0.001), Month 3 1(9%)( P<0.001) and Month 6 3(27%)( P=0.001). There were marked improvements.And at Month 3, bladder wall thickness was (2.75±0.84) mm ( P=0.004), maximal bladder capacity (225.44±94.03) mL ( P=0.041), safe bladder capacity (216.11±106.44) mL ( P=0.049) and bladder compliance (9.43±5.74) mL/cmH 2O ( P=0.023). There were marked improvements.No severe side effects were recorded. Conclusion:An injection of botulinum toxin has marked effects upon bladder capacity and pressure in bladder and helps reduce febrile urinary infection in neurogenic bladder children.And botulinum toxin injection is indicated for individuals not tolerating anticholinergic agents.

INTRODUCTION:Glioblastoma (GBM), the primary malignant tumor in the central nervous system, features high aggressiveness and mortality. Long noncoding RNAs (lncRNAs) can exert the crucial function in regulating various human diseases, including GBM. However, the function and mechanism of lncRNA DLGAP1 antisense RNA 1 (DLGAP1-AS1) in GBM remain still unknown. METHODS:DLGAP1-AS1 expression in GBM cells was detected by RT-qPCR. Functional assays were conducted to determine GBM cell proliferation and apoptosis. RIP, RNA pull down, and luciferase reporter assay were applied for measuring the interplay of DLGAP1-AS1 with other RNAs. RESULTS:DLGAP1-AS1 was distinctly upregulated in GBM cells. DLGAP1-AS1 depletion inhibited cell proliferation, but induced apoptosis. MiR-515-5p could be sponged by DLGAP1-AS1 in GBM cells and to repress cell proliferation in GBM. Further, Rho-associated coiled-coil containing protein kinase 1 (ROCK1) and Nuclear factor erythroid-2 like 1 (NFE2L1) were confirmed as the target gene of miR-515-5p. Wnt signaling pathway could be activated by DLGAP1-AS1 via regulating ROCK1 and NFE2L1 expression. Rescue assays proved that overexpression of both ROCK1 and NFE2L1 could totally reverse the inhibitory effect of silencing DLGAP1-AS1 on GBM cell proliferation. CONCLUSION:LncRNA DLGAP1-AS1 accelerated cell proliferation in GBM via targeting miR-515-5p/ROCK1/NFE2L1 axis and activating Wnt signaling pathway.

Background: Tumor purity is defined as the proportion of cancer cells in the tumor tissue, and its effects on molecular genetics, the immune microenvironment, and the prognosis of children’s central nervous system (CNS) tumors are under-researched.Methods: We applied random forest machine learning, the InfiniumPurify algorithm, and the ESTIMATE algorithm to estimate the tumor purity of every child’s CNS tumor sample in several published pediatric CNS tumor sample datasets from Gene Expression Omnibus (GEO), aiming to perform an integrated analysis on the tumor purity of children’s CNS tumors.Results: Only the purity of CNS tumors in children based on the random forest (RF) machine learning method was normally distributed. In addition, the children’s CNS tumor purity was associated with primary clinical pathological and molecular indicators. Enrichment analysis of biological pathways related to the purity of medulloblastoma (MB) revealed some classical signaling pathways associated with MB biology and development-related pathways. According to the correlation analysis between MB purity and the immune microenvironment, three immune-related genes, namely, CD8A, CXCR2, and TNFRSF14, were negatively related to MB purity. In contrast, no significant correlation was detected between immunotherapy-associated markers, such as PD-1, PD-L1, and CTLA4; most infiltrating immune cells; and MB purity. In the tumor purity–related survival analysis of MB, ependymoma (EPN), and children’s high-grade glioma, we discovered a minor effect of tumor purity on the survival of the aforementioned pediatric patients with CNS tumors.Conclusion: Our purity pediatric pan-CNS tumor analysis provides a deeper understanding and helps with the clinical management of pediatric CNS tumors.

Additional file 8. Pathway analysis of targets of all DEMs.

Abstract Background It is very important to develop a highly efficient cerebrospinal fluid (CSF) detection system with diagnosis and prediction function, for which the detection of circulating tumor cells (CTCs) in CSF is a good choice. In contrast to the past use of epithelial EpCAM as CTCs separation target, a cytoplasm protein of GFAP antibody was first selected to construct highly-sensitive immunomagnetic liposome beads (IMLs). The validation and efficiency of this system in capturing CTCs for brain tumors were measured both in vitro and in vivo. The associations between the numbers of CTCs in patients with their clinical characteristics were further analyzed. Results Our data show that CTCs can be successfully isolated from CSF and blood samples from 32 children with brain tumors. The numbers of CTCs in CSF were significantly higher than those in blood. The level of CTCs in CSF was related to the type and location of the tumor rather than its stage. The higher the CTCs number is, the more possibly the patient will suffer from poor prognosis. Genetic testing in GFAP CTC-DNA by sanger sequencing, q-PCR and NGS methods indicated that the isolated CTCs (GFAP+/EGFR+) are the related tumor cell. For example, the high expression of NPR3 gene in CSF CTCs was consistent with that of tumor tissue. Conclusions The results indicated that GFAP-IML CTCs isolation system, combined with an EGFR immunofluorescence assay of antitumor marker, can serve as a brand-new method for the identification of CTCs for brain tumors. Via lumbar puncture, a minimally invasive procedure, this technique may play a significant role in the clinical diagnosis and drug evaluation of brain tumors.