Identification of oxidative phosphorylation-related genes in moyamoya disease by combining bulk RNA-sequencing analysis and machine learning.

Introduction: Moyamoya disease (MMD) is a chronic cerebrovascular disease that can lead to ischemia and hemorrhagic stroke. The relationship between oxidative phosphorylation (OXPHOS) and MMD pathogenesis remains unknown. Methods: The gene expression data of 60 participants were acquired from three Gene Expression Omnibus (GEO) datasets, including 36 and 24 in the MMD and control groups. Differentially expressed genes (DEGs) between MMD patients MMD and control groups were identified. Machine learning was used to select the key OXPHOS-related genes associated with MMD from the intersection of DEGs and OXPHOS-related gene sets. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), gene set enrichment analysis (GSEA), Immune infiltration and microenvironments analysis were used to analyze the function of key genes. Machine learning selected four key OXPHOS-related genes associated with MMD: CSK, NARS2, PTPN6 and SMAD2 (PTPN6 was upregulated and the other three were downregulated). Results: Functional enrichment analysis showed that these genes were mainly enriched in the Notch signaling pathway, GAP junction, and RNA degradation, which are related to several biological processes, including angiogenesis, proliferation of vascular smooth muscle and endothelial cells, and cytoskeleton regulation. Immune analysis revealed immune infiltration and microenvironment in these MMD samples and their relationships with four key OXPHOS-related genes. APC co-inhibition (p = 0.032), HLA (p = 0.001), MHC I (p = 0.013), T cellco- inhibition (p = 0.032) and Type I IFN responses (p < 0.001) were significantly higher in the MMD groups than those in the control groups. The CSK positively correlated with APC co-inhibition and T cell-co-inhibition. The NARS2 negatively correlated with Type I IFN response. The SMAD2 negatively correlated with APC co-inhibition and Type I IFN response. The PTPN6 positively correlated with HLA, MHC I and Type I IFN responses. Discussion: This study provides a comprehensive understanding of the role of OXPHOS in MMD and will contribute to the development of new treatment methods and exploration of MMD pathogenesis.

Integrating Iso-seq and RNA-seq data for the reannotation of the greater amberjack genome.

The greater amberjack is a very important fishery species with high commercial value, and it is distributed worldwide. Transcriptome-based studies on S. dumerili have been limited by an inadequate reference genome and a lack of well-annotated full-length transcripts. In this study, a total of 12 tissues from juvenile and adult fish both sexes were collected for next-generation RNA sequencing (RNA-seq) and full-length isoform sequencing (Iso-seq). For Iso-seq, a total of 163,218, 149,716, and 189,169 high-quality unique transcript sequences were obtained, with an N50 of 5,441, 5,255, and 5,939, from juvenile, adult male and adult female S. dumerili, respectively. We integrated the Iso-seq and RNA-seq data to construct a comprehensive gene annotation and systematically profiled the dynamics of gene expression across the 12 tissues. Our gene models had greater detail and accuracy than those from NCBI and Ensembl, with more precise polyA locations. These resources serve as a foundation for functional genomic studies and provide valuable insights into the molecular mechanisms underlying the development, reproduction and commercial traits of amberjack.

Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA): study protocol for a randomized controlled trial.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurosurgical emergency with a high mortality rate. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) are delayed products of early brain injury (EBI), which may constitute the principal determinant of an unfavorable patient prognosis. Consequently, the mitigation of DCI and CVS assumes paramount significance in the pursuit of enhanced patient outcomes. However, except for oral nimodipine, there is no effective therapy available in the current guideline. Hence, the exigency arises to proffer novel treatment paradigms. The diversity of hydrogen therapeutic targets has been largely reported in basic research, unveiling its latent capacity to ameliorate EBI in aSAH patients. METHODS: Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA), a single-center, prospective, open-labeled, randomized controlled clinical trial, endeavors to evaluate the efficacy and safety of hydrogen-oxygen gas mixture inhalation therapy in aSAH patients. A cohort of 206 patients will be randomized to either hydrogen-oxygen gas mixture inhalation group (8 h per day, 3 L/min, hydrogen concentration of 67%, oxygen concentration of 33%) or oxygen inhalation group (8 h per day, 3 L/min, oxygen concentration of 33%) within 72 h after aSAH and treated for 7 days in the ICU ward. The primary outcomes are the incidence of DCI and CVS during hospitalization. DISCUSSION: The HOMA aims to evaluate the effectiveness of hydrogen-oxygen gas mixture inhalation therapy in preventing DCI or CVS and improving outcomes in aSAH patients. Notably, this is the first large-scale trial of hydrogen therapy in aSAH patients. Given that the Chinese population represents a significant portion of the global population and the increasing incidence of stroke due to aging, optimizing patient care is vital. Given the current challenges in aSAH patient outcomes, initiating more prospective clinical trials is essential. Recent research has shown hydrogen's therapeutic potential, aligning with EBI in aSAH, driving our exploration of hydrogen therapy's mechanisms in post-aneurysm rupture damage. ETHICS AND DISSEMINATION: The protocol for the HOMA study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University (KY 2022-020-02). All results of the present study will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION: ClinicalTrials.gov NCT05282836. Registered on March 16, 2022.

Lesion-Filling Index from Quantitative DSA Correlates with Hemorrhage of Cerebral AVM.

BACKGROUND AND PURPOSE: Rupture is the most life-threatening manifestation of cerebral AVMs. This study aimed to explore the hemodynamic mechanism of AVM rupture. We introduced a new quantitative DSA parameter that can reflect the degree of intranidal blood stasis, called the lesion-filling index. MATERIALS AND METHODS: This study examined patients with AVMs who had undergone both DSA and MR imaging between 2013 and 2014. Clinical presentations, angioarchitecture, and hemodynamic parameters generated from quantitative DSA were analyzed using univariate and multivariable logistic regression. The lesion-filling index was defined as the arterial diagnostic window divided by the volume of the AVM. To assess the correlation between the lesion-filling index and rupture, we incorporated the lesion-filling index into 2 published prediction models widely recognized for predicting AVM rupture risk, R2eD and VALE. The DeLong test was used to examine whether the addition of the lesion-filling index improved predictive efficacy. RESULTS: A total of 180 patients with AVMs were included. The mean lesion-filling index values in the ruptured group were higher compared with the unruptured group (390.27 [SD, 919.81] versus 49.40 [SD, 98.25]), P < .001). A higher lesion-filling index was significantly correlated with AVM rupture in 3 different multivariable logistic models, adjusting for angioarchitecture factors (OR = 1.004, P = .02); hemodynamic factors (OR = 1.005, P = .009); and combined factors (OR = 1.004, P = .03). Both R2eD (area under the curve, 0.601 versus 0.624; P = .15) and VALE (area under the curve, 0.603 versus 0.706; P < .001) predictive models showed improved predictive performance after incorporating the lesion-filling index and conducting 10-fold cross-validation. CONCLUSIONS: The lesion-filling index showed a strong correlation with AVM rupture, suggesting that overperfusion is the hemodynamic mechanism leading to AVM rupture.

A comprehensive analysis of patients with cerebral arteriovenous malformation with headache: assessment of risk factors and treatment effectiveness.

BACKGROUND: Due to the high mortality and disability rate of intracranial hemorrhage, headache is not the main focus of research on cerebral arteriovenous malformation (AVM), so research on headaches in AVM is still scarce, and the clinical understanding is shallow. This study aims to delineate the risk factors associated with headaches in AVM and to compare the effectiveness of various intervention treatments versus conservative treatment in alleviating headache symptoms. METHODS: This study conducted a retrospective analysis of AVMs who were treated in our institution from August 2011 to December 2021. Multivariable logistic regression analysis was employed to assess the risk factors for headaches in AVMs with unruptured, non-epileptic. Additionally, the effectiveness of different intervention treatments compared to conservative management in alleviating headaches was evaluated through propensity score matching (PSM). RESULTS: A total of 946 patients were included in the analysis of risk factors for headaches. Multivariate logistic regression analysis identified that female (OR 1.532, 95% CI 1.173-2.001, p = 0.002), supply artery dilatation (OR 1.423, 95% CI 1.082-1.872, p = 0.012), and occipital lobe (OR 1.785, 95% CI 1.307-2.439, p < 0.001) as independent risk factors for the occurrence of headaches. There were 443 AVMs with headache symptoms. After propensity score matching, the microsurgery group (OR 7.27, 95% CI 2.82-18.7 p < 0.001), stereotactic radiosurgery group(OR 9.46, 95% CI 2.26-39.6, p = 0.002), and multimodality treatment group (OR 8.34 95% CI 2.87-24.3, p < 0.001) demonstrate significant headache relief compared to the conservative group. However, there was no significant difference between the embolization group (OR 2.24 95% CI 0.88-5.69, p = 0.091) and the conservative group. CONCLUSIONS: This study identified potential risk factors for headaches in AVMs and found that microsurgery, stereotactic radiosurgery, and multimodal therapy had significant benefits in headache relief compared to conservative treatment. These findings provide important guidance for clinicians when developing treatment options that can help improve overall treatment outcomes and quality of life for patients.

Stratified assessment of treatment approach for craniocervical junction arteriovenous fistulas: a multicenter cohort study and literature review.

OBJECTIVE: Craniocervical junction arteriovenous fistulas (CCJ-AVFs) are complex vascular shunts that present a challenge for treatment. The aim of this study was to compare the clinical outcomes of microsurgery and endovascular embolization for CCJ-AVFs and to determine whether the treatment approach affected the obliteration rate and neurological improvement. METHODS: The authors conducted a retrospective analysis of 64 patients who had undergone microsurgery or endovascular embolization for CCJ-AVF at one of two neurosurgical centers from January 2014 to February 2022. Additionally, a pooled analysis of 68 patients from 38 studies was performed. Baseline characteristics, angioarchitectural features, and clinical outcomes were compared between two treatment groups. A subgroup analysis of CCJ-AVFs with carotid artery (CA) feeders was also performed. RESULTS: In the multicenter cohort, the complete obliteration rate was 95.1% with microsurgery, 81.8% with embolization via the CA, and 50.0% with embolization via the vertebral artery (VA). After adjusting for baseline and confounding features, the occlusion rate was significantly lower in the VA embolization group (adjusted OR 41.06, 95% CI 2.37-711.9, p = 0.01). No new-onset infarctions occurred in the microsurgical group, whereas 1 patient each in the CA and VA embolization groups experienced posttreatment infarction. Microsurgery demonstrated a neurological improvement rate similar to that in the CA embolization group (65.9% vs 63.6%, respectively). In the subgroup analysis of CCJ-AVF with CA feeders in the multicenter cohort, the occlusion rate and neurological improvement in the CA embolization group were comparable to those in the microsurgery group. The subgroup analysis in the pooled analysis revealed complete obliteration rates of 100.0% in the microsurgical group, 88.9% in the CA embolization group, and 66.7% in the VA embolization group. CONCLUSIONS: This study supports microsurgery as the best treatment modality for CCJ-AVFs, exhibiting the highest rates of complete obliteration. Conversely, embolization via the VA can result in a lower occlusion rate and less neurological improvement. In CCJ-AVFs with CA feeders, embolization via the CA can be a safe and effective alternative to microsurgery.

Elevated cortical blood flow insufficiency volume as a predictor of adverse outcomes in aneurysmal subarachnoid hemorrhage: a large prospective quantitative computed tomography perfusion study.

PURPOSE: Early hypoperfusion changes exist in patients with aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate a readily obtainable quantitative computed tomography perfusion (CTP) parameter that could assist in quickly identifying patients at risk of delayed cerebral ischemia (DCI) and poor 90-day functional outcomes on admission. METHODS: We prospectively collected data between 2021.04 and 2022.12. Preoperative CTP data were post-processed using RAPID software. The cortical blood flow insufficiency (CBFI) was defined as Time-to-maximum > 4.0 s. Patients were categorized into four groups according to CBFI volume distribution. To minimize differences among the groups, we employed stabilized inverse probability of treatment weighting (sIPTW). The primary outcome was DCI and poor 90-day functional outcomes (modified Rankin Scale, 3-6) was the secondary outcome. Multivariable Cox or Logistic analysis were performed to estimate the association between CBFI volume and the study outcomes, both before and after sIPTW. RESULTS: At baseline, the mean (SD) age of the 493 participants was 55.0 (11.8) years, and 299 (60.6%) were female. One hundred and seven participants with DCI and eighty-six participants with poor 90-day functional outcomes were identified. After sIPTW, CBFI volume demonstrated a significant association with DCI (Cox regression: Group 4 versus Group 1, HR 3.69, 95% CI 1.84-7.01) and poor 90-day functional outcomes (Logistic regression: Group 4 versus Group 1, OR 4.61, 95% CI 2.01-12.50). CONCLUSION: In this study, an elevated preoperative CBFI volume was associated with adverse outcomes in aSAH patients. More well-designed studies are needed to confirm this association.

[Imaging risk factors for postoperative cerebral infarction in adults with ischemic Moyamoya disease].

Objective: To investigate the imaging factors associated with postoperative cerebral infarction in adult patients aged 18 and above with ischemic Moyamoya disease. Methods: The clinical data of adult patients who underwent surgeries for ischemic Moyamoya disease in the Department of Neurosurgery at Peking University International Hospital from October 2015 to October 2020 were retrospectively analyzed. Of the 239 patients, 120 were male and 119 were female, with ages ranging from 18 to 63 (41.7±10.3) years. A total of 239 patients(290 cases) underwent direct and indirect combined revascularization (CR).Gender, age, surgical side, preoperative transient ischemic attack (TIA), presence of old cerebral infarction, and imaging features were compared between the patients with (48 cases) and without (242 cases) cerebral infarction within 1 week after surgery. Multivariate logistic binary regression model was used to analyze the imaging risk factors of postoperative cerebral infarction. Results: Cerebral infarction occurred in 48 cases(16.5%) among the 290 CR group within 1 week after surgery. The proportion of patients with TIA, old cerebral infarction, ICA stenosis, A1 segment stenosis, M1 segment stenosis, abnormal posterior cerebral artery (PCA), and unstable compensation before CR in the cerebral infarction group was higher than that in the non-cerebral infarction group (P<0.05).Preoperative TIA (OR=4.514, 95%CI: 1.920-10.611), old cerebral infarction (OR=2.856,95%CI:1.176-6.936), A1 stenosis (OR=7.027,95%CI:1.877-26.308), M1 stenosis (OR=6.968,95%CI:2.162-22.459), abnormal PCA (OR=4.114,95%CI:1.330-12.728)and unstable compensation (OR=4.488,95%CI:1.194-16.865) were risk factors for cerebral infarction after CR surgery (all P<0.05). Conclusion: Among the imaging factors, TIA, old cerebral infarction, A1 stenosis, M1 stenosis, abnormal PCA and unstable compensation were risk factors for cerebral infarction in adult patients with ischemic Moyamoya disease treated by combined revascularization.

Immune landscape and progress in immunotherapy for pituitary neuroendocrine tumors.

Pituitary neuroendocrine tumors (pitNETs) are the second most common primary brain tumors. Despite their prevalence, the tumor immune microenvironment (TIME) and its clinical implications remain largely unexplored. This review provides a comprehensive overview of current knowledge on the immune landscape and advancements in targeted immunotherapy for pitNETs. Macrophages and T cells are principal immune infiltrates within the TIME. Different subtypes of pitNETs display distinct immune patterns, influencing tumor progressive behaviors. PD-L1, the most extensively studied immune checkpoint, is prominently expressed in hormonal pitNETs and correlates with tumor growth and invasion. Cytokines and chemokines including interleukins, CCLs, and CXCLs have complex correlations with tumor subtypes and immune cell infiltration. Crosstalk between macrophages and pitNET cells highlights bidirectional regulatory roles, suggesting potential macrophage-targeted strategies. Recent preclinical studies have demonstrated the efficacy of anti-PD-L1 therapy in a mouse model of corticotroph pitNET. Moreover, anti-PD-1 and/or anti-CTLA-4 immunotherapy has been applied globally in 28 cases of refractory pitNETs, showing more favorable responses in pituitary carcinomas than aggressive pitNETs. In conclusion, the TIME of pitNETs represents a promising avenue for targeted immunotherapy and warrants further investigation.

Bulk and single cells transcriptomes with experimental validation identify USP18 as a novel glioma prognosis and proliferation indicator.

The mechanism by which ubiquitin-specific protease 18 (USP18) (enzyme commission: 3.4.19.12) inhibition in cancer promotes cell pyroptosis via the induction of interferon (IFN)-stimulated genes has been recently demonstrated. It is also known that USP18 influences the epithelial-mesenchymal transition of glioma cells. In the present study, the upregulation of USP18 in glioma was revealed through bulk transcriptome analysis, which was associated with poor prognosis in patients with glioma. Furthermore, USP18 levels affected the response to immunotherapy in patients with glioma. Single-cell transcriptome and enrichment analyses demonstrated that USP18 was associated with type 1 IFN responses in glioma T cells. To demonstrate the effect of USP18 expression levels on glioma cells, USP18 expression was knocked down in U251 and U87MG ATCC cell lines. A subsequent Cell Counting Kit-8 assay revealed that glioma cell viability was significantly decreased 4 days after USP18 knockdown. In addition, the knockdown of USP18 expression significantly inhibited the clonogenicity of U251 and U87MG ATCC cells. In conclusion, the present study demonstrated that knockdown of USP18 expression inhibited the proliferation of glioma cells, which may be mediated by the effect of USP18 on the IFN-I response.

Risk factors for delayed postoperative hemorrhage in patients with brain arteriovenous malformations: an analysis of the nationwide multicenter prospective registry MATCH study.

OBJECTIVE: Reducing the incidence of delayed postoperative hemorrhage (DPH) is one of the challenges in the surgical treatment of patients with brain arteriovenous malformations (bAVMs). This study aimed to identify several risk factors for DPH after bAVM resection and evaluate the impact of these risk factors in patients with bAVMs. METHODS: The authors retrospectively reviewed consecutive patients with bAVMs who underwent microsurgical resection between August 2011 and September 2021. Patients were divided into either the DPH group or non-DPH group based on whether they experienced a postoperative intracerebral hemorrhage into the bAVM bed within 14 days after bAVM resection. Factors associated with DPH were assessed using multivariate logistic regression analyses. RESULTS: A total of 1284 consecutive patients with bAVMs were evaluated; DPH events occurred in 18 patients (1.4%). There were several differences in vascular architecture between the two cohorts. A giant nidus, a nidus involved in the eloquent area, a periventricular nidus, and a nidus accompanied by venous ectasia were more likely to be associated with DPH events. The multivariate analysis identified two independent factors associated with DPH: maximum diameter (OR 1.44 per 1-cm increase, 95% CI 1.13-1.83) and periventricular lesion (OR 4.10, 95% CI 1.33-12.59). The area under the receiver operating characteristic curve for the maximum lesion diameter and development of DPH was 0.71 (95% CI 0.58-0.84). The cutoff value for the maximum bAVM diameter was 4.15 cm. Furthermore, patients with a giant bAVM, of which the maximum diameter was ≥ 4.15 cm, had a higher DPH risk after surgery (HR 5.79, 95% CI 2.01-16.67; p < 0.01). The incidence rates of DPH for patients with periventricular lesions were higher than those for patients without periventricular lesions (HR 4.50, 95% CI 1.77-11.40; p < 0.01). CONCLUSIONS: Patients with giant bAVMs or periventricular lesions are at higher risk for DPH after surgery. Strategies such as blood pressure control, preoperative embolization, intraoperative monitoring, and careful patient selection should be considered to reduce the risk of DPH in high-risk patients.

Overloaded transnidal pressure gradient as the hemodynamic mechanism leading to arteriovenous malformation rupture: a quantitative analysis using intravascular pressure monitoring and color-coded digital subtraction angiography.

BACKGROUND: The hemodynamics of brain arteriovenous malformations (AVMs) may have implications for hemorrhage. This study aimed to explore the hemodynamics of ruptured AVMs by direct microcatheter intravascular pressure monitoring (MIPM) and indirect quantitative digital subtraction angiography (QDSA). METHODS: We recruited patients with AVMs at a tertiary neurosurgery center from October 2020 to March 2023. In terms of MIPM, we preoperatively super-selected a predominant feeding artery and main draining vein through angiography to measure intravascular pressure before embolization. In processing of QDSA, we adopted previously standardized procedure for quantitative hemodynamics analysis of pre-embolization digital subtraction angiography (DSA), encompassing main feeding artery, nidus, and the main draining vein. Subsequently, we investigated the correlation between AVM rupture and intravascular pressure from MIPM, as well as hemodynamic parameters derived from QDSA. Additionally, we explored the interrelationships between hemodynamic indicators in both dimensions. RESULTS: After strict screening of patients, our study included 10 AVMs (six ruptured and four unruptured). We found that higher transnidal pressure gradient (TPG) (53.00±6.36 vs 39.25±8.96 mmHg, p=0.042), higher feeding artery pressure (FAP) (72.83±5.46 vs 65.00±6.48 mmHg, p=0.031) and higher stasis index of nidus (3.54±0.73 vs 2.43±0.70, p=0.043) were significantly correlated with AVM rupture. In analysis of interrelationships between hemodynamic indicators in both dimensions, a strongly positive correlation (r=0.681, p=0.030) existed between TPG and stasis index of nidus. CONCLUSIONS: TPG and FAP from MIPM platform and nidus stasis index from QDSA platform were correlated with AVM rupture, and both were positively correlated, suggesting that higher pressure load within nidus may be the central mechanism leading to AVM rupture.

Effects of calcium channel blockers on perioperative ischemic events in hypertensive patients with intracranial aneurysms undergoing neurointervention.

BACKGROUND: Although calcium channel blockers (CCBs) are useful in stroke prevention, their specific role in preventing stroke in hypertensive patients with intracranial aneurysms undergoing endovascular stent placement remains unclear. METHODS: We retrospectively examined 458 hypertensive patients with intracranial aneurysms who underwent stent treatment, drawn from a larger multicenter cohort comprising 1326 patients across eight centers. Patients were dichotomized into two groups according to use of a CCB. Propensity score matching (PSM) was performed to balance group differences in patient and aneurysm characteristics. We conducted a comparison of patient and aneurysm characteristics, ischemic complications, and clinical outcomes between the two groups. RESULTS: The CCB and non-CCB groups comprised 279 and 179 patients, respectively. PSM resulted in 165 matched pairs. After PSM, the incidence of ischemic events within 1 month of the procedure (4.2% vs 10.9%; P=0.022) and proportion of patients with modified Rankin Scale score >2 at last follow-up (1.5% vs 7.8%; P=0.013) were significantly lower in the CCB group. Among patients treated with combination therapy, inclusion of a CCB was associated with a lower incidence of ischemic events (1.5% vs 13.3%; P=0.345), but the difference was not statistically significant after correction. CONCLUSIONS: CCB use in hypertensive patients undergoing endovascular stenting for treatment of intracranial aneurysms is associated with a lower incidence of ischemic events and a lower incidence of unfavorable neurological outcomes, especially when used in combination therapy.

Evaluation of cerebrovascular reactivity in moyamoya disease using oxygen-dependent magnetic resonance imaging.

Moyamoya disease (MMD) is a rare cerebrovascular disorder marked by progressive stenosis of the internal carotid arteries. Assessing cerebral hemodynamics, specifically cerebrovascular reactivity (CVR), is vital for MMD management and prognosis. In this study, fMRI was performed in a prospective cohort of 47 patients with MMD and 32 healthy controls to investigate its utility in evaluating CVR and to explore the influence of cerebral posterior circulation compensation on CVR in MMD. The regions where the CVR values of participants with MMD were lower than those of healthy controls were primarily concentrated in the frontal, parietal, and temporal lobes (p < 0.05). In certain regions mainly supplied by posterior circulation, the CVR values of compensatory-normal subgroup tended to exceed those of compensatory-poor subgroup. fMRI can detect a significant decrease in CVR values in patients with MMD compared to healthy controls. Compensation for the posterior cerebral circulation may affect cerebrovascular reactivity.

The novel HLA-C*14:02:01:33 allele identified by Pacific Biosciences HiFi sequencing in a Chinese individual.

HLA-C*14:02:01:33 differs from HLA-C*14:02:01:01 by one nucleotide substitution in intron 2.

A retrospective study on the relationship between serum electrolyte disorder and delayed cerebral infarction after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Delayed cerebral ischemia (DCI)-induced cerebral infarction is a major cause of adverse neurological outcomes following aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to investigate the relationship between postoperative serum electrolyte levels and DCI in patients with aSAH. MATERIALS AND METHODS: We analyzed the data of patients with aSAH between 2015 and 2022. The patients were classified into two groups according to whether they experienced DCI. Electrolyte levels were categorized into three groups based on the normal ranges for electrolytes. Logistic regression models were used to study the relationship between electrolyte levels and DCI. Another logistic regression analysis was conducted to explore the relationship between the different severity levels of statistically significant indicators and DCI. A restrictive cubic spline model was adopted to assess the potential linear relationship between electrolytes and DCI. Subsequently, sensitivity analysis was performed to assess the impact of collinearity among ions. Finally, subgroup analysis was performed. RESULTS: This study included 1,099 patients. Patients with hyperchloremia were more prone to DCI than those with normal chloride levels. Subsequently, excluding the population with hypochloremia, both mild and severe hyperchloremia were found to be associated with an increased risk of DCI compared with normal chloride levels. Within the framework of a restrictive cubic spline, our findings revealed an increased incidence of DCI (P for nonlinear = 0.735) as chloride levels increased. Sensitivity analysis revealed that patients with severe hyperchloremia were more susceptible to DCI. CONCLUSIONS: This study found that patients with aSAH and postoperative hyperchloremia are more prone to developing DCI.

DTX2 promotes glioma development via regulation of HLTF.

BACKGROUND: Human Deltex 2 (DTX2) is a ubiquitin E3 ligase that functions as an oncogene and has been shown to participate in many human cancers. However, the role of DTX2 in glioma progression has remained obscure. In this study, we explore the mechanism underlying the function of DTX2 in glioma progression. METHODS: The associations between DTX2 expression and clinical characteristics of glioma were determined by bioinformatic analysis of data from The Cancer Genome Atlas and Human Protein Atlas. The expression of DTX2 in glioma tissues was detected using immunohistochemistry and western blotting. Lentivirus-mediated gene knockdown and overexpression were used to determine the effects of DTX2 and helicase-like transcription element (HLTF) on glioma cell proliferation and migration with CCK-8, cell colony formation, transwell, and wound healing assays; flow cytometry in vitro; and animal models in vivo. The interaction of the DTX2 and HLTF proteins was verified by immunoprecipitation assay and confocal microscopy. RESULTS: DTX2 was highly expressed in glioma samples, and this was correlated with worse overall survival. Silencing of DTX2 suppressed glioma cell viability, colony formation, and migration and induced cell apoptosis. In vitro ubiquitination assays confirmed that DTX2 could downregulate HLTF protein levels by increasing ubiquitination of the HLTF protein. We also observed that HLTF inhibited proliferation and migration of glioma cells. Subcutaneous xenografts with DTX2-overexpressing U87 cells showed significantly increased tumor volumes and weights. CONCLUSIONS: We have identified DTX2/HLTF as a new axis in the development of glioma that could serve as a prognostic or therapeutic marker.

Timing of microsurgical resection for ruptured brain arteriovenous malformations: a propensity score-matched analysis using prospective single-center registry data.

OBJECTIVE: The optimal microsurgical timing in ruptured brain arteriovenous malformations (AVMs) is not well understood and is surrounded by controversy. This study aimed to elucidate the impacts of microsurgical resection timing on clinical outcomes. METHODS: The authors retrieved and reviewed the records on all ruptured AVMs treated at their institution and registered in a nationwide multicenter prospective collaboration registry between August 2011 and August 2021. Patients were dichotomized into an early resection group (≤ 30 days from the last hemorrhagic stroke) and a delayed resection group (> 30 days after the last hemorrhagic stroke). Propensity score-matched analysis was used to compare long-term outcomes. The primary outcome was neurological status as assessed using the modified Rankin Scale (mRS). The secondary outcomes were complete obliteration rate, postoperative seizure, and postoperative hemorrhage. RESULTS: Of the 3649 consecutive AVMs treated at the authors' institution, a total of 558 ruptured AVMs were microsurgically resected and had long-term follow-up. After propensity score matching, 390 ruptured AVMs (195 pairs) were included in the comparison of outcomes. The mean (± standard deviation) clinical follow-up duration was 4.93 ± 2.94 years in the early resection group and 5.61 ± 2.56 years in the delayed resection group. Finally, as regards the distribution of mRS scores, short-term neurological outcomes were better in the delayed resection group (risk difference [RD] 0.3%, 95% CI -0.1% to 0.6%, p = 0.010), whereas long-term neurological outcomes were similar between the two groups (RD 0.0%, 95% CI -0.2% to 0.2%, p = 0.906). Long-term favorable neurological outcomes (early vs delayed: 90.8% vs 90.3%, p > 0.999; RD 0.5%, 95% CI -5.8% to 6.9%; RR 1.01, 95% CI 0.94-1.07) and long-term disability (9.2% vs 9.7%, p > 0.999; RD -0.5%, 95% CI -6.9% to 5.8%; RR 0.95, 95% CI 0.51-1.75) were also similar between these groups. In terms of secondary outcomes, postoperative seizure (early vs delayed: 8.7% vs 5.6%, p = 0.239; RD 3.1%, 95% CI -2.6% to 8.8%; RR 1.55, 95% CI 0.74-3.22), postoperative hemorrhage (1.0% vs 1.0%, p > 0.999; RD 0.0%, 95% CI -3.1% to 3.1%; RR 1.00, 95% CI 0.14-7.04), and hospitalization time (16.4 ± 8.5 vs 19.1 ± 7.9 days, p = 0.793) were similar between the two groups, whereas early resection had a lower complete obliteration rate (91.3% vs 99.0%, p = 0.001; RD -7.7%, 95% CI -12.9% to 3.1%; RR 0.92, 95% CI 0.88-0.97). CONCLUSIONS: Early and delayed resection of ruptured AVMs had similar long-term neurological outcomes. Delayed resection can lead to a higher complete obliteration rate, although the risk of rerupture during the resection waiting period should be vigilantly monitored.

Pipeline Embolization Device for intracranial aneurysms presenting with mass effect: a large Chinese cohort.

BACKGROUND: Unruptured intracranial aneurysm treatment aims to reduce the risk of aneurysm rupture and bleeding, relieves symptoms and improve the quality of life for patients. This study aimed to assess the safety and efficacy of Pipeline Embolization Device (PED, Covidien/Medtronic, Irvine, CA) treatment for intracranial aneurysms presenting with mass effect in real-world settings. METHODS: We selected patients from the PED in China Post-Market Multi-Center Registry Study with mass effect presentation. The study endpoints included postoperative mass effect deterioration and mass effect relief at follow-up (3-36 months). We conducted multivariate analysis to identify factors associated with mass effect relief. Subgroup analyses by aneurysm location, size and form were also performed. RESULTS: This study included 218 patients with a mean age of 54.3±11.8 years and a female predominance of 74.0% (162/218). The postoperative mass effect deterioration rate was 9.6% (21/218). During a median follow-up period of 8.4 months, the mass effect relief rate was 71.6% (156/218). Notably, immediate aneurysm occlusion following treatment was significantly associated with mass effect relief (OR 0.392, 95% CI, 0.170 to 0.907, p=0.029). Subgroup analysis demonstrated that adjunctive coiling contributed to mass effect relief in cavernous aneurysms, while dense embolism impeded symptom relief in aneurysms<10 mm and saccular aneurysms. CONCLUSIONS: Our data confirmed the efficacy of PED in relieving mass effect. The findings of this study provide support for endovascular treatment to alleviate mass effect in unruptured intracranial aneurysms. TRIAL REGISTRATION NUMBER: NCT03831672.