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With the aging of the global population, accumulating interest is focused on manipulating the fundamental aging‐related signaling pathways to delay the physiological aging process and eventually slow or prevent the appearance or severity of multiple aging‐related diseases. Recently, emerging evidence has shown that RNA modifications, which were historically considered infrastructural features of cellular RNAs, are dynamically regulated across most of the RNA species in cells and thereby critically involved in major biological processes, including cellular senescence and aging. In this review, we summarize the current knowledge about RNA modifications and provide a catalog of RNA modifications on different RNA species, including mRNAs, miRNAs, lncRNA, tRNAs, and rRNAs. Most importantly, we focus on the regulation and roles of these RNA modifications in aging‐related diseases, including neurodegenerative diseases, cardiovascular diseases, cataracts, osteoporosis, and fertility decline. This would be an important step toward a better understanding of fundamental aging mechanisms and thereby facilitating the development of novel diagnostics and therapeutics for aging‐related diseases. RNA modificaitons in aging‐related diseases

Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.

PurposeThe aim of this study was to thoroughly analyze the clinical characteristics of a large cohort of spinal meningioma (SM) from a single neurological center and identify risk factors associated with worse progression free survival and neurological function outcome.MethodsClinical information was retrieved from 483 SM and 9806 cranial meningioma cases who were operated in our center between 2003 and 2013. 194 SM patients who were followed at the main branch were used for prognostic analyses that included both recurrence free survival and neurological functions based on Modified McCormick scale (MMS).ResultsFemales were predominant (P < 0.001). High grade tumors were not common (WHO grade II, 2.9%; grade III, 1.7%), while the clear cell subtype was frequent within grade II SMs (6/14, 42.9%). Macroscopic total resection was achieved in all SMs (Simpson grade I, 30.9%; grade II, 65.5%; grade III, 3.6%) with a low complications rate (4.6%) and provided neurological improvement in 80 patients (41.2%). Recurrence was seen in 9 cases (4.6%) and associated with high WHO grade, male, prior recurrence, and Simpson grade III. High WHO grade and high Ki-67 index were identified to be independent factors predictive of both neurological function deterioration and impaired post-operative neurological status.ConclusionsOur analysis of the largest SM cohort in scale from a single institution offers a comprehensive view of the clinical characteristics of surgically treated SM, revealing the distinct biology of SM in comparison to its cranial counterparts, and providing guidance to improve surgical management of SM.

Radiation resistance significantly hinders the efficacy of radiotherapy for meningiomas, posing a primary obstacle. The clinical inadequacy of therapeutic drugs and radiosensitizers for treating meningiomas further exacerbates the challenge. Therefore, the aim of this study was to identify potential radiosensitizers for treating meningiomas. A high content clonogenic survival drug screening was employed to evaluate 166 FDA-approved compounds across varied concentration ranges. Cell viability, apoptosis, and radiosensitization were assessed using CCK-8 assays, Annexin V-FITC/PI assays and standard colony formation assays. Transcriptome sequencing, immunofluorescence and cell cycle experiments were conducted to assess transcriptional profile, DNA double-strand break damage and cell cycle distribution. Finally, the radiosensitizing effect of Maytansine was assessed through subcutaneous tumor implantation in nude mice. The proportion of maytansine exhibiting SRF≥1.5 within the detectable concentration range was 100%. CCK-8 assay indicated the IC50 values of maytansine for IOMM-Lee and CH157 were 0.26 ± 0.06 nM and 0.31 ± 0.01 nM, respectively. Standard clonogenic survival assays and Annexin V-FITC/PI assays revealed maytansine had a notable radiosensitizing effect on meningioma cells. Transcriptome sequencing analysis demonstrated that maytansine can modulate cell cycle and DNA damage repair. Immunofluorescence analysis of γ-H2AX and cell cycle experiments demonstrated that Maytansine enhances DNA double-strand breaks and induces G2/M phase arrest. Moreover, studies had indicated that Maytansine augments the therapeutic efficacy of radiotherapy. This study highlighted the potential of maytansine as a potent inhibitor and radiosensitizer for meningiomas by inducing G2/M phase cell cycle arrest and enhancing DNA double-strand break damage. These findings opened up a promising path in the development of radiosensitizers aimed at treating this condition.

Background Meningioma represents the most common intracranial tumor in adults. However, it is rare in pediatric patients. We aimed to demonstrate the clinicopathological characteristics and long-term outcome of pediatric meningiomas (PMs). Method We enrolled 74 patients with intracranial PMs and analyzed their clinicopathological characteristics. Targeted next generation sequencing was used to detect alterations in meningioma relevant genes. Progression-free survival (PFS) was compared between PMs and adult meningiomas (AMs). Univariate and multivariate Cox analyses were employed to evaluate the predictive values of clinicopathological characteristics. A nomogram was constructed and its predictive accuracy evaluated. Result 40 females (54.1%) and 34 males (45.9%) patients, with the gender ratio of 1.18:1, were identified. 9 (12.2%) cases were clinically diagnosed as NF2-related Schwannomatosis (NF2-SWN), while 65 (87.8%) were sporadic. Ventricular location was found in 16 patients (21.6%). 19 patients (25.7%) experienced recurrence during a median follow-up period of 33 months (range 2 -145.25 months). The 3-, 5-, and 8-year PFS rates was 74.74%, 74.74%, and 59.38%, respectively. The PFS of the PM and AM cohorts were not significantly different, with or without propensity score matching. NF2 mutation was observed in 33 sporadic PMs (52.4%), whereas alterations in other genes ( AKT1 , TRAF7 , SMO , PIK3CA , KLF4 ) frequently mutated in AMs, were not identified. The proportion of NF2 mutation in PMs was significantly lower in the skull base than other locations ( p  = 0.02). One anaplastic PM harbored TERT promoter mutation. Of note, in sporadic PMs, NF2 mutations were not significantly associated with PFS ( p  = 0.434) or overall survival (OS) ( p  = 0.60). The multivariate Cox analysis showed NF2-SWN ( p  < 0.001) and extent of resection ( p  = 0.013) to be independently associated with the PFS of PMs. Our prognostic model showed predictive accuracy for long-term PFS in PMs as the 3-, 5- and 8-year Area Under the Curve (AUC) was 0.927, 0.930, and 0.870, respectively. Conclusion PM was characterized by its relative male predominance, ventricular location, NF2-SWN, and NF2 mutation. Of note, PMs had similar prognosis to AMs and NF2 alteration was not significantly associated with PFS in PMs.

PurposeThe aim of this study was to systematically analyze the clinical characteristics of a large cohort of parasagittal meningioma (PM) and to evaluate the patients’ outcomes and best treatment strategies based on tumor features.MethodsTo minimize selection bias we performed a single-institutional review of PM with restricted criteria. One hundred and ninety-two consecutive patients who met criteria for inclusion were reviewed from 2003 to 2011 in our general hospital.ResultsA total of 131 cases (68.2%) were with WHO grade I, while grade II and grade III PMs constituted 40 (20.8%) and 21 cases (10.9%). Higher histological grade was associated with loss of trimethylation of H3K27 (P = 0.000). For WHO grade I PMs, GTR was significantly associated with a better PFS (P = 0.023); however, adjuvant radiotherapy did not benefit patients with STR (P = 0.215). For de novo high-grade (WHO grade II and III) PMs (n = 37), adjuvant radiotherapy was associated with a significantly longer OS (P = 0.013), while no difference was observed between GTR and STR (P = 0.654). In recurrent high-grade PM patients (n = 24), GTR combined with adjuvant radiotherapy increased PFS (P = 0.005).ConclusionsThis study demonstrated that PMs were a heterogeneous group of tumors with a high proportion of high-grade tumors that often displayed aggressive clinical behaviors. Low-grade PM benefited from radical resection, whereas high-grade de novo PM did not. Adjuvant radiotherapy significantly prolonged OS for high-grade primary PM, but did not impact survival of patients with subtotally resected low-grade tumors. Long-term outcome of high-grade recurrent PMs was dismal. We thus show that extent of tumor resection, tumor grade and tumor recurrent status inform therapeutic decisions for PMs.

Background Intracranial solitary fibrous tumor (SFT) is a rare mesenchymal tumor of fibroblastic origin in the central nervous system (CNS). The 2021 WHO classification of CNS tumor has updated the entity and grading criterion of SFT. We aimed to compare the 2021 WHO grading criterion (2021-WGC) and 2016 WHO grading criterion (2016-WGC) for their value to predict prognosis and radiotherapy (RT) efficacy. Methods This is a retrospective study involving 223 consecutive intracranial SFT patients who received tumor resection at our neurosurgical center from 2013 to 2021. Univariable and multivariable Cox regression analyses were utilized to identify prognosis-related factors and evaluate the efficacy of RT. A risk model was constructed to predict the long-term recurrence. Results A total of 223 SFT patients were included in this study. During a median follow-up period of 4.67 years, 80 (35.9%) patients experienced tumor recurrence and 14 (6.3%) experienced extracranial metastasis. Patients with SFT who developed recurrence were significantly older at diagnosis and exhibited higher Ki-67 index and mitotic count. Of note, the PFS of 2016-WGC grade 3 tumors was worse than the comparable PFS of grade 1 and 2 tumors ( P  = 0.001), while the PFS of 2021-WGC grade 1 tumors was better than grade 2 and 3 tumors that showed similar PFS in the long term ( P  < 0.001). We further proposed a novel risk stratification method that demonstrated a superior prognostic value compared to the 2021-WGC and 2016-WGC. Additionally, RT significantly prolonged the PFS of SFT patients, especially beyond 3 years after surgery ( P  = 0.032). Further efficacy analysis showed that RT prolonged PFS in the 2016-grade 3 tumors. While with the 2021-WGC and novel risk stratification, RT prolonged PFS in the 2021-grade 2 and intermediate risk tumors, respectively. Conclusions The 2016-WGC identified high-recurrence risk patients in grade 3 while the 2021-WGC identified low-recurrence risk patients in grade 1. RT significantly prolonged PFS in SFT patients, especially after 3 years post-surgery. Notably, RT significantly improved PFS in the 2016-grade 3, 2021-grade 2 and intermediate risk tumors.

The effect of adjuvant radiotherapy in management for high‐grade meningiomas, especially atypical meningiomas, remains controversial. We aimed to explore the role of adjuvant radiotherapy in this population. A total of 162 adults with high‐grade meningiomas (99 atypical meningiomas and 63 anaplastic meningiomas) were treated from 2003 to 2008 at Huashan Hospital. One hundred and seventeen patients presented with primary and 45 with recurrent disease. One hundred and fifteen patients (70.9%) were treated with adjuvant radiotherapy after surgical resection. The median follow‐up was 76.5 months (range 1‐142 months). Kaplan‐Meier survival curve and Cox proportional hazards modeling were used for analyses. Adjuvant radiotherapy was associated with prolonged progression‐free survival (PFS) and overall survival (OS) in patients with newly diagnosed anaplastic meningiomas irrespective of extent of resection (PFS, P = .001; OS, P = .003). Gross total resection was the only independent prognostic factor for those with newly diagnosed atypical meningiomas (PFS, P < .001; OS, P = .012). A survival benefit for adjuvant radiation was also found in subgroup analysis of patients with high‐grade meningiomas who underwent subtotal resection (PFS, P = .023; OS, P = .013). Among recurrent high‐grade meningiomas, radiotherapy offered no statistically significant improvement in either PFS or OS. Adjuvant radiotherapy is associated with improved survival in patients with newly diagnosed anaplastic meningiomas and those high‐grade meningiomas following subtotal resection. However, there was no significant correlation identified between postoperative radiation and outcome for recurrent high‐grade meningiomas. Future prospective randomized trials may help clarify the optimal tailored treatment for patients with high‐grade meningioma. The article focuses on the prognostic value of postoperative radiation in patients with atypical or anaplastic meningioma. We demonstrate that adjuvant radiotherapy is associated with improved survival in patients with high‐grade meningiomas following subtotal resection. However, postoperative radiation was not associated with significant improvement in outcome for patients with recurrent high‐grade meningiomas. The article focuses on the prognostic value of postoperative radiation in patients with atypical or anaplastic meningioma. We demonstrate that adjuvant radiotherapy is associated with improved survival in patients with high‐grade meningiomas following subtotal resection. However, postoperative radiation was not associated with significant improvement in outcome for patients with recurrent high‐grade meningiomas.

BackgroundHigh-grade meningiomas (HGMs; World Health Organization [WHO] classification grade II and III) have high relapse rates and poor clinical outcomes despite surgery and radiation treatments. No effective medical therapy currently exists for HGMs, and developing novel therapeutic strategies depends on the identification of molecular drivers. In cancer, β1 integrin enhances malignant characteristics, including proliferation, invasion, and drug resistance.ObjectiveWe conducted this study to investigate whether β1 integrin could be a therapeutic target in HGMs.Patients and MethodsExpression of β1 integrin was examined in gene array datasets, with proteomics of clinical meningioma specimens, and in patient-derived HGM xenografts. Anti-tumor activity of OS2966, a first-in-class humanized antagonizing monoclonal antibody against β1 integrin, was tested in vitro and in vivo using an orthotopic mouse model of patient-derived malignant meningioma.Resultsβ1 integrin was expressed in meningiomas of all WHO grades and two xenografts tested. In vitro, OS2966 suppressed the viability of NF2-deficient MN3 sphere cells and NF2-wild-type IOMM-Lee malignant meningioma cells only when plated on laminin-coated plastic. While OS2966 decreased phosphorylation of ERK1/2 in both MN3 cells and laminin-grown IOMM-Lee cells, OS2966 only affected the phosphorylation of FAK (Tyr397) in MN3, and of Akt (Ser473) in IOMM-Lee cells, respectively, indicating differential pathway inhibition. Systemic administration of OS2966 in mice bearing orthotopic MN3 HGMs inhibited HGM cell proliferation and significantly extended overall survival of the treated mice.Conclusionsβ1 Integrin may be a therapeutic target in HGMs, and further preclinical and clinical development of OS2966 for HGM therapy is warranted.

Objective: This study aims to evaluate the potential role of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in detecting high-grade meningiomas and predicting the prognosis of patients after meningioma surgery. Patients and methods: A total of 124 patients met the final inclusion criterion. Tumor to gray ratio (TGR) was compared with Ki-67 labeling index, and its correlations with pre-operative neurological function and treatment status were also evaluated. Receiver-operating characteristic (ROC) curve was drawn to determine a cut-off value which could discriminate meningioma of different grades. Prognostic factors including TGR were analyzed using Kaplan-Meier survival curve and cox proportional model. Results: The TGR of higher World Health Organization (WHO) grade meningioma was significantly higher than that in lower grade (p < 0.001), and it was correlated with the Ki-67 labeling index (p < 0.001, r = 0.1545). The TGR of 1.30 was the best cutoff value for the detection of high grade (WHO grade II&III) meningioma from low grade (WHO grade I) according to ROC analysis, with a sensitivity of 61.5%, the specificity of 86.7%, and accuracy of 81.5%. The TGR (p < 0.001), treatment status (p = 0.035), tumor grade (p < 0.001) and Ki-67 labeling index (p < 0.001) were significantly associated with progression-free survival (PFS). Cox proportional hazards model demonstrated that TGR (p = 0.013) was an independent prognostic factor for PFS. Conclusion: A high uptake of FDG was correlated with a more proliferative biological behavior and is a risk factor for tumor recurrence.