Glioblastoma (GBM) represents one of the most challenging tumor types to treat clinically, characterized by an exceedingly poor patient prognosis. This is primarily attributable to the ambiguous molecular mechanisms that hinder the advancement of targeted therapies. Here, PRMT3 is identified as a key driver of tumorigenesis in GBM. Bioinformatics and clinical data reveal that high expression of PRMT3 in glioma cells is closely correlated with poor patient prognosis. Functional experiments demonstrate that PRMT3 overexpression enhances the proliferative capacity of GBM cells. Mechanistically, PRMT3 interacts with Y-box binding protein 1 (YBX1), and catalyzes the arginine methylation of YBX1 protein at R69 within its cold-shock domain. Subsequently, it was found that methylated YBX1 binds to 5-methylcytosine (m5C)-modified E2F1 mRNA and stabilizes its transcription, significantly promoting the expression of E2F1. The resulting PRMT3-YBX1-E2F1 axis sustains high E2F1 protein levels, activates a proliferation-associated transcriptional program, and is essential for GBM cell proliferation in vitro and in vivo . Meanwhile, the PRMT3 inhibitor SGC707 and the non-methylated YBX1 peptide significantly inhibited the proliferation of GBM cells. Our findings underscore that PRMT3 stabilizes E2F1 transcription through methylation of YBX1 at R69, promoting GBM tumorigenesis, and highlight the PRMT3-YBX1-E2F1 axis as a potential therapeutic target for GBM treatment.
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, underscoring the need to identify tumor-suppressive regulators for the development of more effective therapies. Circular RNAs (circRNAs) have emerged as important regulators in cancers, yet their roles in GBM remain incompletely understood. In this study, we identified circular NLK (circNLK; hsa_circ_0002103) as a tumor suppressor in GBM. circNLK expression was downregulated in GBM relative to normal brain tissues, and higher circNLK expression associated with better patient outcomes. Ectopic circNLK overexpression inhibited GBM cell proliferation and motility while increasing apoptosis. Mechanistically, circNLK bound to the RNA-binding protein hnRNP L in an m6A-dependent manner and competed with the RGS16 RNA transcript for hnRNP L binding, thereby reducing RGS16 stability and expression. In orthotopic mouse models of GBM, circNLK overexpression delayed tumor growth, prolonged survival, and reduced RGS16 expression in tumor tissues. Together, these findings expand our understanding of circRNAs as tumor suppressors and provide a rationale for exploring circNLK-based therapeutic strategies in GBM.
Patients with atlantoaxial dislocation combined with atlas occipitalization often present with variations in the anatomy of the vertebral artery and bone, posing potential risks during the implantation of the C2 pedicle screws during surgery. Based on comprehensive preoperative imaging evaluation, this study investigates the blood supply, course, and relationship with bone of the vertebral artery in patients with atlantoaxial dislocation combined with atlas occipitalization, aiming to provide reference for safe implantation of internal fixation. Imaging data of 77 patients with atlantoaxial dislocation combined with atlas occipitalization from October 2015 to December 2023 at the First Affiliated Hospital of the University of Science and Technology of China were collected, including CT, CT angiography, and MRI. The blood supply, course, and relationship with surrounding structure of the vertebral artery were analyzed using PACS and RadiAnt software. There were 18 males and 59 females, with an average age of 48.5 ± 10.5 years (range: 17–71 years). Forty-one cases (53.2
To present our experience in the surgical management of completely extradural dumbbell spinal schwannomas with a new surgical strategy. This study is a case series of patients treated at the Neurosurgery Department of the First Affiliated Hospital of USTC, between January 2018 and June 2021. 24 patients met the inclusion criteria, with cervical and lumbar spines being the most frequent locations. All patients underwent surgical treatment. Total gross resection was accomplished in all patients. Two cases had numbness and no case exhibited motor deficit. There was no postoperative CSF leakage or wound infection. Based on a limited number of observations, we conclude that our technique was feasible and effective for the treatment of extradural dumbbell spinal schwannomas. http://www.chictr.org.cn/ , No. ChiCTR2400086171.
Methods: During the period January 2020 to September 2022, fifteen patients underwent posterior occipitocervical fixation in our department. All patients had unilateral HRVA on at least one side that prohibited the insertion of C2 pedicle screws. There were 2 males and 13 females aged 47 +/- 11.9 years (range: 17-64 years). After the correction of the vertical dislocation during the operation, the C2 pedicle screw insertion and occipitocervical fixation and fusion were performed using the vertebral artery mobilization technique. A routine three-dimensional reconstructed CT examination was executed to confirm the trajectory of C2 pedicle screws post-operation, and a CT angiography examination was performed when necessary. Neurological function was assessed using the Japanese Orthopedic Association (JOA) scale. The preoperative and postoperative JOA score and the main radiological measurements, including anterior atlantodental interval (ADI), the distance of odontoid tip above Chamberlain line, and clivus-canal angle (CCA), were collected and compared by paired t-test. Results: All 15 patients had atlas assimilation, among which 12 patients had C2-C3 fusion (Klippel-Feil syndrome). Mobilization of the HRVA was successfully completed, and C2 pedicle screws were then fulfilled after the vertebral artery was protected. There was no injury to the vertebral artery during the operation. Meanwhile, no severe surgical complications such as cerebral infarction or aggravated neurological dysfunction occurred during the perioperative period. Satisfactory C2 pedicle screw placement and reduction were reached in all 15 patients. All the patients achieved bone fusion 6 months after surgery. No looseness and shift of internal fixation or reduction loss was observed during the follow-up period. Compared to the preoperative, the postoperative JOA score and the main radiological measurements were remarkably improved and statistically significant. Conclusions: C2 pedicle screw insertion assisted by mobilization of the vertebral artery is safe and considerably effective, providing a choice for internal fixation in cases with high-riding vertebral arteries.
BACKGROUND:To review the treatment and the causes of postoperative epidural hematoma (PEDH) after intracranial tumor resection.METHOD:A retrospective case study was conducted to examine a series of patients who developed PEDH as a complication following intracranial tumor resection between January 2016 and June 2021. The study collected data from hospital charts, including clinical status at admission, imaging results, histopathologic findings, surgical management, complications, and outcomes. Causes of PEDH were evaluated through a review of operative notes and discussions with the surgical team.RESULTS:Twenty-five patients (10 males, 15 females; median age 42 years, range 11-61 years; median medical history 27 months, range 1-96 months) were enrolled in the study. Regarding tumor location, 16 cases exhibited supratentorial brain tumors, 4 cases had infratentorial brain tumors, 2 cases of tumors occurred in the petroclival region, 2 cases in the peritorcular region, and 1 case in the pineal region. Four of these cases were complicated with supratentorial hydrocephalus. The 25 cases in this study were classified into four types based on location. Type 1 refers to EDHs that occur at the adjacent site of the operative field without involvement of the surgical area. Type 2 includes hematomas that occur at the adjacent site of the surgical area and the surgical area. Type 3 includes EDHs that occur in distant areas, and type 4 involves EDHs in the surgical field. The numbers of cases of types 1, 2, 3, and 4 PEDHs were 16, 2, 3, and 4 cases, respectively. Most PEDHs were associated with reduced ICP after craniotomy due to intracranial tumor resection and substantial loss of CSF. All patients achieved satisfactory outcomes after hematoma evacuation.CONCLUSION:The decrease in ICP resulting from intracranial tumor resection and CSF loss might lead to PEDHs. By employing optimized surgical techniques and meticulous patient management to prevent rapid decreases in ICP and dural detachment, we can potentially lower the incidence of PEDHs. Additionally, prompt evacuation of hematomas can contribute to positive outcomes.
Purpose. To present our experience with retractorless surgery for resection of petroclival meningiomas (PCMs) via the subtemporal approach with routine operative instruments. Methods. Clinical data of patients with PCMs who received surgical treatments via subtemporal approach were retrospectively analyzed. Patient demographics, duration of operation, extent of resection, postoperative brain injury rate, postoperative complication, and surgical outcome were reviewed. Results. Twenty-nine consecutive patients with retractorless surgery via subtemporal approach performed between November 2018 and November 2021. The gross total resection rate was 82.8% ( N = 24 ). The incidence of postoperative temporal lobe injury was 3.4% ( N = 1 ). All the procedures were completed without fixed retraction or other specialized instruments. Conclusions. Retractorless surgery via subtemporal approach is a reliable treatment option for PCMs, which can be completed with routine operative instruments.
Background Introduction: Nail injuries are important causes of penetrating craniocerebral injuries. Theirs incidence is very low, but the injuries can be fatal. Since the nail gun was gradually popularized in 1959, the incidence of nail injuries has been increasing. Here we report a case of nail gun injury to superior sagittal sinus and review the literature of the past 60 years to find out what are the possible factors of nail gun injury and what are their respective ratios? Clinical Report: An 18-year-old male patient was accidentally injured in the head by the worker's nail gun, accompanied by scalp pain, no physical sensation disorder, and consciousness disorder. A computed tomography scan of his skull showed the penetrating site at the right frontal area, near the superior sagittal sinus. Seven days later, the patient underwent a successful surgery without neurological sequelae. Discussion: Nail injuries are rare, but can be potentially fatal. We found that nail guns were the main cause of nail injuries, and other causes include occupational injury, violence, lack of supervision of young children (potential for domestic violence, and child abuse), mental illness, and suicide attempts. While paying attention to the anatomical location of trauma, clinicians should also think more about the possibility of injury so as to provide better help to patients in time.
Circular RNAs (circRNAs) are usually enriched in neural tissues, yet about 80% circRNAs have lower expression in gliomas relative to normal brains, highlighting the importance of circRNAs as tumor suppressors. However, the clinical impact as well as the pathways regulated by the tumor-suppressive circRNAs remain largely unknown in glioblastoma (GBM). Through bioinformatic analysis followed by experimental validation, we found that hsa_circ_0114014 (circLRRC7) was dramatically down-regulated in GBM when compared with normal brain tissues (p < 0.0001). GBM patients with a lower circLRRC7 expression had poorer progression-free survival (PFS, p < 0.05) and overall survival (OS, p < 0.05). Analyses of the predicted target miRNAs of circLRRC7 in CSCD and CRI databases, in combination with the miRNA expression data in GBMs and normal brains from GSE database, revealed miR-1281 as a potential downstream target of circLRRC7. Subsequently, the target genes of hsa-mir-1281 were predicted by TargetScan, miRDB and miRNATAR databases. Intersection analysis and correlation test indicated that PDXP was a potential target of miR-1281. In summary, circLRRC7 may be a tumor suppressor that associated with miR-1281 and PDXP expression in GBM, which may provide novel therapeutic targets for GBM treatment.
Whether surgical revascularization can prevent recurrent hemorrhage in hemorrhagic moyamoya disease (HMD) patients remains a matter of debate. This study mainly aims at the comparison of treatment effect between surgical revascularization and conservative treatment of adult HMD patients. We retrospectively enrolled 322 adult HMD patients, including 133 in revascularization group and 189 in conservative group. The revascularization group included patients who underwent combined (n = 97) or indirect revascularization alone (n = 36). Ninety-two and forty-one patients underwent unilateral and bilateral revascularization respectively. The modified Rankin scale (mRS) was used to assess the functional status. The comparison was made based on initial treatment paradigm among two categories: (1) revascularization vs. conservative, (2) unilateral vs. bilateral revascularization. The rebleeding rate was significantly lower in revascularization group than that in conservative group (14.3% vs. 27.0%, P = 0.007). As for the functional outcomes, the average mRS was significantly better in revascularization group (1.7 ± 1.5) than that in conservative group (2.8 ± 1.9) (P < 0.001). The death rate in revascularization group was 8.3% (11/133), comparing to 20.1% (38/189) in conservative group (P = 0.004). While comparing between unilateral and bilateral revascularization within the revascularization group, the result demonstrated lower annual rebleeding rate in bilateral group (0.5%/side-year) than that in unilateral group (3.3%/side-year) (P = 0.001). This study proved the better treatment efficacy of surgical revascularization than that of conservative treatment in HMD patients, regarding both in rebleeding rate and mortality rate. Furthermore, bilateral revascularization seems more effective in preventing rebleeding than unilateral revascularization.
BACKGROUND:In adult patients with moyamoya disease (MMD) underwent combined revascularization, cerebral infarction during the acute postoperative phase is common and can lead to neurological dysfunction after revascularization in MMD patients. The aim of this study was to share the experience of individualized perioperative blood pressure (BP) management for adult MMD patients in one single center.METHODS:We retrospectively reviewed 144 adult patients with MMD who underwent 186 procedures of combined revascularization at our institution from March 2013 to July 2019. Clinical features and outcomes were analyzed, in particular regarding cerebral infarction and hyperperfusion syndrome (HPS). All of the patients received individualized management perioperatively, especially about the blood pressure management according to the characteristics of moyamoya disease.RESULTS:Postoperative cerebral infarction and HPS within 14 days after revascularization were recorded. Cerebral infarction occurred in four (2.1%) procedures among four patients. No patients suffered from a malignant cerebral infarction and only one patient had permanent neurological deficits. The incidence of HPS was 10.8% and no one presented with intracranial hemorrhage. All of the symptoms were reversible without any brain parenchymal injury.CONCLUSIONS:Our findings suggest that we can decrease the incidence and extent of cerebral infarction in adult MMD patients following combined revascularization by individualized perioperative BP management.
Carcinoma of the kidney is one of the most prevalent carcinoma worldwide. The majority types of carcinoma are clear cell renal cell carcinoma (CCRCC), which consist more than 80% of the cases. As a genetically diverse disease, identification of prognosis-related genes has utmost importance in the early diagnosis and prognosis of the CCRCC. In this study, we performed gene expression profiling to identify prognosis-related genes for CCRCC. In addition, we developed and validated a gene signature-based risk score to comprehensively assess the prognostic function of differentially expressed genes. Furthermore, we performed a ROC analysis to identify the optimal cut-off point for classification risk level of the patients. Univariate Cox regression models were used to assess the association between differentially expressed genes in relation to the prognosis of patients with different stages of CCRCC. Five genes were identified significantly differentially expressed in CCRCC and associated with their survival time, namely: IDUA, NDST1, SAP30L, CRYBA4, and SI. A 5-gene signature-based risk score was developed based on the Cox coefficient of the individual genes. The prognostic value of this risk score was validated in an internal testing data set. In summary, a gene-based risk score was identified and validated, which can predict CCRCC patient survival. The potential functions of this gene expression signature and individual differentially expressed gene as prognostic targets of CCRCC were revealed by this study. Furthermore, these findings may have important implications in the understanding of the potential therapeutic method for the CCRCC patients.