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BACKGROUND: Intracranial aneurysms (IAs) pose a significant and intricate challenge. Elucidating the interplay between DNA methylation and IA pathogenesis is paramount to identify potential biomarkers and therapeutic interventions. METHODS: We employed a comprehensive bioinformatics investigation of DNA methylation in IA, utilizing a transcriptomics-based methodology that encompassed 100 machine learning algorithms, genome-wide association studies (GWAS), Mendelian randomization (MR), and summary-data-based Mendelian randomization (SMR). Our sophisticated analytical strategy allowed for a systematic assessment of differentially methylated genes and their implications on the onset, progression, and rupture of IA. RESULTS: We identified DNA methylation-related genes (MRGs) and associated molecular pathways, and the MR and SMR analyses provided evidence for potential causal links between the observed DNA methylation events and IA predisposition. CONCLUSION: These insights not only augment our understanding of the molecular underpinnings of IA but also underscore potential novel biomarkers and therapeutic avenues. Although our study faces inherent limitations and hurdles, it represents a groundbreaking initiative in deciphering the intricate relationship between genetic, epigenetic, and environmental factors implicated in IA pathogenesis.
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Aneurisma Intracraniano , Multiômica , Humanos , Aneurisma Intracraniano/genética , Metilação de DNA/genética , Epigenoma , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Aprendizado de MáquinaRESUMO
Objective: Investigate the potential correlation between the age of initial sexual contact, the lifetime accumulation of sexual partners, and the occurrence of intracranial aneurysm (IA) employing a two-sample Mendelian randomization approach. Methods: This research aims to elucidate the causal relationship between intracranial aneurysm (IA) and sexual variables. Two distinct sexual variables, specifically the age had first sexual intercourse (n = 406,457) and the lifetime number of sexual partners (n = 378,882), were employed as representative parameters in a two-sample Mendelian randomization (MR) study. Outcome data from 23 cohorts, comprising 5,140 cases and 71,934 controls, were gathered through genome-wide association studies (GWAS). To bolster analytical rigor, five distinct methodologies were applied, encompassing MR-Egger technique, weighted median, inverse variance weighted, simple modeling, and weighted modeling. Results: Our investigation unveiled a causal relationship between the age first had sexual intercourse and the occurrence of intracranial aneurysm (IA), employing the Inverse Variance Weighted (IVW) approach [Odds Ratio (OR): 0.609, p-value: 5.684E-04, 95% Confidence Interval (CI): 0.459-0.807]. This association was notably significant in the context of unruptured intracranial aneurysms (uIA) using the IVW approach (OR: 0.392, p-value: 6.414E-05, 95% CI: 0.248-0.621). Conversely, our findings did not reveal any discernible link between the lifetime number of sexual partners and the occurrence of IA (IA group: OR: 1.346, p-value: 0.415, 95% CI: 0.659-2.749; SAH group: OR: 1.042, p-value: 0.943, 95% CI: 0.338-3.209; uIA group: OR: 1.990, p-value: 0.273, 95% CI: 0.581-6.814). Conclusion: The two-sample Mendelian Randomization (MR) study presented herein provides evidence supporting a correlation between the age of initial engagement in sexual activity and the occurrence of intracranial aneurysm (IA), with a noteworthy emphasis on unruptured intracranial aneurysms (uIA). Nevertheless, our investigation failed to establish a definitive association between IA and the cumulative lifetime number of sexual partners.
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BACKGROUND: The risk of intracranial aneurysms (IAs) is increased in individuals with depression and anxiety. This indicates that depression and anxiety may contribute to the development of physical disorders. Herein, to investigate the association between genetic variants related to depression and anxiety and the risk of IA, two-sample Mendelian randomization was performed. METHODS: The genome-wide association study (GWAS) comprised genome-wide genotype data of 2248 clinically well-characterized patients with anxiety and 7992 ethnically matched controls from four European countries. Sex-specific summary-level outcome data were obtained from the GWAS of IA, including 23 cohorts with a total of 10,754 cases and 306,882 controls of European and East Asian ancestry. To improve validity, five varying Mendelian randomization techniques were used in the analysis, namely Mendelian randomization-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode. RESULTS: The inverse variance weighted results indicated the causal effect of depression on IA (P = 0.03, OR = 1.32 [95 % CI, 1.03-1.70]) and unruptured IA (UIA) (P = 0.02, OR = 1.68 [95 % CI, 1.08-2.61]). However, the causal relationship between depression and subarachnoid hemorrhage (SAH) was not found (P = 0.16). We identified 43 anxiety-associated single-nucleotide polymorphisms as genetic instruments and found no causal relationship between anxiety and IA, UIA, and SAH. LIMITATIONS: Potential pleiotropy, possible weak instruments, and low statistical power limited our findings. CONCLUSION: Our MR study suggested a possible causal effect of depression on the increased risk of UIAs. Future research is required to investigate whether rational intervention in depression treatment can help to decrease the societal burden of IAs.
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Aneurisma Intracraniano , Feminino , Masculino , Humanos , Aneurisma Intracraniano/genética , Depressão/epidemiologia , Depressão/genética , Estudo de Associação Genômica Ampla , Ansiedade/epidemiologia , Ansiedade/genética , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/genética , Análise da Randomização MendelianaRESUMO
Autophagy is considered a double-edged sword, with a role in the regulation of the pathophysiological processes of the central nervous system (CNS) after cerebral ischemia-reperfusion injury (CIRI). The 18-kDa translocator protein (TSPO) is a highly conserved protein, with its expression level in the nervous system closely associated with the regulation of pathophysiological processes. In addition, the ligand of TSPO reduces neuroinflammation in brain diseases, but the potential role of TSPO in CIRI is largely undiscovered. On this basis, we investigated whether TSPO regulates neuroinflammatory response by affecting autophagy in microglia. In our study, increased expression of TSPO was detected in rat brain tissues with transient middle cerebral artery occlusion (tMCAO) and in BV2 microglial cells exposed to oxygen-glucose deprivation or reoxygenation (OGD/R) treatment, respectively. In addition, we confirmed that autophagy was over-activated during CIRI by increased expression of autophagy activation related proteins with Beclin-1 and LC3B, while the expression of p62 was decreased. The degradation process of autophagy was inhibited, while the expression levels of LAMP-1 and Cathepsin-D were significantly reduced. Results of confocal laser microscopy and transmission electron microscopy (TEM) indicated that autophagy flux was disordered. In contrast, inhibition of TSPO prevented autophagy over-activation both in vivo and in vitro. Interestingly, suppression of TSPO alleviated nerve cell damage by reducing reactive oxygen species (ROS) and pro-inflammatory factors, including TNF-α and IL-6 in microglia cells. In summary, these results indicated that TSPO might affect CIRI by mediating autophagy dysfunction and thus might serve as a potential target for ischemic stroke treatment.
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Isquemia Encefálica , Traumatismo por Reperfusão , Ratos , Animais , Isquemia Encefálica/complicações , Fatores de Transcrição , Infarto da Artéria Cerebral Média/complicações , Traumatismo por Reperfusão/prevenção & controle , AutofagiaRESUMO
Background: DNA methylation is an important epigenetic modification that affects genomic instability and regulates gene expression. Long non-coding RNAs (lncRNAs) modulate gene expression by interacting with chromosomal modifications or remodelling factors. It is urgently needed to evaluate the effects of DNA methylation-related lncRNAs (DMlncRNAs) on genome instability and further investigate the mechanism of action of DMlncRNAs in mediating the progression of lower-grade gliomas (LGGs) and their impact on the immune microenvironment. Methods: LGG transcriptome data, somatic mutation profiles and clinical features analysed in the present study were obtained from the CGGA, GEO and TCGA databases. Univariate, multivariate Cox and Lasso regression analyses were performed to establish a DMlncRNA signature. The KEGG and GO analyses were performed to screen for pathways and biological functions associated with key genes. The ESTIMATE and CIBERSORT algorithms were used to determine the level of immune cells in LGGs and the immune microenvironment fraction. In addition, DMlncRNAs were assessed using survival analysis, ROC curves, correlation analysis, external validation, independent prognostic analysis, clinical stratification analysis and qRT-PCR. Results: We identified five DMlncRNAs with prognostic value for LGGs and established a prognostic signature using them. The Kaplan-Meier analysis revealed 10-years survival rate of 10.10% [95% confidence interval (CI): 3.27-31.40%] in high-risk patients and 57.28% (95% CI: 43.17-76.00%) in low-risk patients. The hazard ratio (HR) and 95% CI of risk scores were 1.013 and 1.009-1.017 (p < 0.001), respectively, based on the univariate Cox regression analysis and 1.009 and 1.004-1.013 (p < 0.001), respectively, based on the multivariate Cox regression analysis. Therefore, the five-lncRNAs were identified as independent prognostic markers for patients with LGGs. Furthermore, GO and KEGG analyses revealed that these lncRNAs are involved in the prognosis and tumorigenesis of LGGs by regulating cancer pathways and DNA methylation. Conclusion: The findings of the study provide key information regarding the functions of lncRNAs in DNA methylation and reveal that DNA methylation can regulate tumour progression through modulation of the immune microenvironment and genomic instability. The identified prognostic lncRNAs have high potential for clinical grouping of patients with LGGs to ensure effective treatment and management.
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Background: Immunogenic Cell Death (ICD) is a novel way to regulate cell death and can sufficiently activate adaptive immune responses. Its role in immunity is still emerging. However, the involvement of ICD in Intracranial Aneurysms (IA) remains unclear. This study aimed to identify biomarkers associated with ICDs and determine the relationship between them and the immune microenvironment during the onset and progression of IA. Methods: The IA gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in IA were identified and the effects of the ICD on immune microenvironment signatures were studied. Techniques like Lasso, Bayes, DT, FDA, GBM, NNET, RG, SVM, LR, and multivariate analysis were used to identify the ICD gene signatures in IA. A consensus clustering algorithm was used for conducting the unsupervised cluster analysis of the ICD patterns in IA. Furthermore, enrichment analysis was carried out for investigating the various immune responses and other functional pathways. Along with functional annotation, the weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network and module construction, identification of the hub gene, and co-expression analysis were also carried out. Results: The above techniques were used for establishing the ICD gene signatures of HMGB1, HMGN1, IL33, BCL2, HSPA4, PANX1, TLR9, CLEC7A, and NLRP3 that could easily distinguish IA from normal samples. The unsupervised cluster analysis helped in identifying three ICD gene patterns in different datasets. Gene enrichment analysis revealed that the IA samples showed many differences in pathways such as the cytokine-cytokine receptor interaction, regulation of actin cytoskeleton, chemokine signaling pathway, NOD-like receptor signaling pathway, viral protein interaction with the cytokines and cytokine receptors, and a few other signaling pathways compared to normal samples. In addition, the three ICD modification modes showed obvious differences in their immune microenvironment and the biological function pathways. Eight ICD-regulators were identified and showed meaningful associations with IA, suggesting they could severe as potential prognostic biomarkers. Conclusions: A new gene signature for IA based on ICD features was created. This signature shows that the ICD pattern and the immune microenvironment are closely related to IA and provide a basis for optimizing risk monitoring, clinical decision-making, and developing novel treatment strategies for patients with IA.
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Proteína HMGB1 , Proteína HMGN1 , Aneurisma Intracraniano , Teorema de Bayes , Biomarcadores , Quimiocinas/genética , Biologia Computacional/métodos , Conexinas , Perfilação da Expressão Gênica/métodos , Proteína HMGB1/genética , Humanos , Morte Celular Imunogênica , Interleucina-33/genética , Aneurisma Intracraniano/genética , Aprendizado de Máquina , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas do Tecido Nervoso , Proteínas Proto-Oncogênicas c-bcl-2/genética , Receptores de Citocinas/genética , Receptor Toll-Like 9/genética , Proteínas Virais/genéticaRESUMO
Background: The role of epigenetic modulation in immunity is receiving increased recognition-particularly in the context of RNA N6-methyladenosine (m6A) modifications. Nevertheless, it is still uncertain whether m6A methylation plays a role in the onset and progression of intracranial aneurysms (IAs). This study aimed to establish the function of m6A RNA methylation in IA, as well as its correlation with the immunological microenvironment. Methods: Our study included a total of 97 samples (64 IA, 33 normal) in the training set and 60 samples (44 IA, 16 normal) in the validation set to systematically assess the pattern of RNA modifications mediated by 22 m6A regulators. The effects of m6A modifications on immune microenvironment features, i.e., immune response gene sets, human leukocyte antigen (HLA) genes, and infiltrating immune cells were explored. We employed Lasso, machine learning, and logistic regression for the purpose of identifying an m6A regulator gene signature of IA with external data validation. For the unsupervised clustering analysis of m6A modification patterns in IA, consensus clustering methods were employed. Enrichment analysis was used to assess immune response activity along with other functional pathways. The identification of m6A methylation markers was identified based on a protein-protein interaction network and weighted gene co-expression network analysis. Results: We identified an m6A regulator signature of IGFBP2, IGFBP1, IGF2BP2, YTHDF3, ALKBH5, RBM15B, LRPPRC, and ELAVL1, which could easily distinguish individuals with IA from healthy individuals. Unsupervised clustering revealed three m6A modification patterns. Gene enrichment analysis illustrated that the tight junction, p53 pathway, and NOTCH signaling pathway varied significantly in m6A modifier patterns. In addition, the three m6A modification patterns showed significant differences in m6A regulator expression, immune microenvironment, and bio-functional pathways. Furthermore, macrophages, activated T cells, and other immune cells were strongly correlated with m6A regulators. Eight m6A indicators were discovered-each with a statistically significant correlation with IA-suggesting their potential as prognostic biological markers. Conclusion: Our study demonstrates that m6A RNA methylation and the immunological microenvironment are both intricately correlated with the onset and progression of IA. The novel insight into patterns of m6A modification offers a foundation for the development of innovative treatment approaches for IA.
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OBJECTIVE: This study aims to discuss the safety and short-term efficacy of endovascular treatment on high-risk patients with chronic carotid artery occlusion. METHODS: A retrospective analysis was performed on the clinical data of 16 high-risk patients with chronic carotid artery occlusion who received endovascular treatment at the Department of Neurosurgery of the First Affiliated Hospital of Xinjiang Medical University from November 2013 to July 2016. The incidence of adverse events at 1 week, 30 days and six months post-operation were observed, and NIHSS was adopted to assess the neurological function of patients six months before and after the operation. Follow-up time was 6-26 months, with an average of 18.4 months. RESULTS: The degree of carotid artery stenosis of these 16 patients was 100%. The degree of which after the operation was 24.9 ± 17.0%; and the difference was statistically significant (P<0.05). Iatrogenic carotid artery dissection occurred in one case, and persistent hypotension and sinus bradycardia occurred in one case. Furthermore, one case of endovascular treatment was not approved to be opened. Afterwards, temporal artery-STA-MCA bypass was performed; upon postoperative head CTA and DSA, the result showed that the perfusion was good. One case refused to undergo surgical treatment. The NHSS score of 14 cases of endovascular treatment that were successfully opened six months after the operation was 2.0 ± 1.36, which improved (P<0.05) compared with that of pre-operation. CONCLUSION: Endovascular treatment on high-risk patients with chronic carotid artery occlusion is safe and effective. And it has obvious curative effect in short mid-term. KEY WORDS: Arterial occlusive disease, Carotid artery, Endovascular treatment, Treatment outcome.
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Estenose das Carótidas , Procedimentos Endovasculares , Artéria Carótida Primitiva , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Humanos , Estudos Retrospectivos , Artérias Temporais , Resultado do TratamentoRESUMO
INTRODUCTION: Lymphangioleiomyomatosis (LAM) is a rare disease which affects women of reproductive age almost exclusively as one of the most gender-specific diseases, and which can occur at any site in the body but most commonly in the lungs. Here we report a rare case of recurrent brain lymphangiomyoma which was misdiagnosed as angiomyxoma. CASE PRESENTATION: A 28-year-old male complained of finding a recurrent mass at the right temporal lobe of his brain for the last 4 months. He had undergone a resection of a brain mass two years prior. One year after the operation, the mass recurred again and was resected another time. Both of the operations were performed in another hospital and he was postoperatively diagnosed with angiomyxoma. This time the patient underwent a third operation in our hospital to remove the lesion, which was confirmed as lymphangiomyoma. Unfortunately, the patient again discovered a re-emerging mass at the primary operation site on the 50th day post-surgically. CONCLUSION: There is currently no effective cure for LAM and treatment options and relevant literature remain limited. Hence other potential therapeutic targets need to be identified.
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BACKGROUND: The purpose of this study is to report the treatment approaches and postoperative outcomes of extracranial carotid artery aneurysms (ECAAs) and discuss the symptoms, related risk factors, etiology, diagnostic methods, treatments, and follow-up period complications. CASE PRESENTATION: We describe three patients with symptomatic extracranial carotid artery aneurysms; one of them was treated with end-to-end anastomosis of the extracranial internal carotid artery (EICA) after the resection of the aneurysm, while the other two patients were deployed with Willis covered stents in the extracranial internal carotid artery. All of the patients were in good condition when discharged home. After a mean follow-up period of 8 months, all the patients were alive and only one of them had the neurologic deficit. Additionally, we reviewed the relative literatures. CONCLUSION: Both of the surgical and endovascular treatments have relatively satisfactory outcomes in ECAA patients. However, it is necessary to provide individualized treatments to different patients according to the characteristics of the aneurysms.
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OBJECTIVE: To observe the short-term efficacy of Pipeline embolization divice (PED) for the treatment of complex intracranial aneurysms. METHODS: The clinical data of 29 consecutive patients with 32 intracranial aneurysms treated with PED between April 2015 to September 2016 were analyzed retrospectively. There were 3 small aneurysm, 15 large aneurysms, 8 giant aneurysms, 5 fusiform ayneurysms and 1 recidivation. The vessels include 25 anterior circulation and 4 posterior circulation. RESULTS: We treated 31 aneurysms with 30 PEDs and all of the stents were implanted successfully. 1 case of single aneurysm was multiple divices implanted and 1 case of 3 aneurysms were treated by single PED. 12 of the 29 patients were implanted PED only, 17 were implanted PED with coils, 2 underwent balloon remodeling after the PED implanted. The ostia of 19 ophthalmic arteries, 10 posterior communicating arteries, 4 posterior inferior cerebellar arteries and 1 anterior cerebral artery were covered by PED during procedures; 1 ophthalmic arteries and 1 posterior communicating artery disappeared, no branch vessels occlusion and parent artery stenosis occurred.Hemorrhagic complacations occurred in 2 patients, 2 hours and 5 days after procedure respectively. Radiographic follow-up examnations were carried out in 24 patients and revealed complete occlusion in 21 patients, uncomplete occlusion in 3 patients. No neurological injure occurred in 27 patients who received a clinical follow-up. CONCLUSION: PED provide a safe and effective methord for the treatment of intracranial complex aneurysms like wide-neck aneurysms, fusiform aneurysms, giant aneurysms in low risk of procedural complications and high rates of aneurysm occlusion.
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Embolização Terapêutica/instrumentação , Procedimentos Endovasculares/instrumentação , Aneurisma Intracraniano/terapia , Stents , Adolescente , Adulto , Idoso , Embolização Terapêutica/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Feminino , Seguimentos , Humanos , Aneurisma Intracraniano/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Cerebral vasospasm (CVS) is the most common neurological complication after aneurysmal subarachnoid hemorrhage (aSAH) and associated with poor functional outcome and mortality. Reports on incidence and predictors of CVS in Chinese patients with aSAH were scarce. We aimed to estimate the incidence and predictors of angiographic vasospasm (AV), symptomatic vasospasm (SV), and cerebral infarction in Chinese patients with aSAH. METHODS: We retrospectively reviewed the medical records of 542 consecutive aSAH patients admitted to neurosurgery department of the First Affiliated Hospital of Xinjiang Medical University in Urumqi city of China between January 1, 2011 and December 31, 2015. AV, SV and cerebral infarction were defined based on clinical data and neuroimaging findings. Univariate and multivariate analyses were performed to identify predictors of AV, SV or cerebral infarction. RESULTS: 343 (63.3%) patients fulfilled the inclusion and exclusion criteria. Of them, 182(53.1%) developed AV, 99 (28.9%) developed SV, and 87 (25.4%) developed cerebral infarction. A history of hypertension, poor modified Fisher grade (3-4) and poor Hunt-Hess grade (4-5) on admission were common risk factors for AV, SV and cerebral infarction. Patients from Uyghur ethnic group or other minorities were less likely to develop AV, SV or cerebral infarction, compared to those from Han ethic group after adjustment of other potential confounders. Additionally, age ≥53 years, leukocyte count ≥11× 109/L on admission and being current or former smokers were independent risk factors of cerebral infarction. Leukocyte count ≥11× 109/L on admission and aneurysm size ≥ 10 mm were independent risk factors of SV. Serum glucose level ≥7.0 mmol/L on admission was an independent risk factor of AV. CONCLUSION: Risk factors of different definitions of CVS were diverse in Chinese patients with aSAH; however, risk factors of SV and cerebral infarction seem to be similar. We recommend early and aggressive therapy in these patients at-risk of CVS.
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Infarto Cerebral/epidemiologia , Infarto Cerebral/etiologia , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/epidemiologia , Vasoespasmo Intracraniano/epidemiologia , Vasoespasmo Intracraniano/etiologia , Angiografia , China , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnóidea/diagnóstico por imagem , Vasoespasmo Intracraniano/diagnóstico por imagemRESUMO
AIM: This study aimed to investigate the operative procedure for neuroendoscope-assisted microscopic resection of petroclival meningioma to improve prognosis. MATERIAL AND METHODS: Twelve patients with petroclival meningioma who had undergone neuroendoscope-assisted microscopic resection at the Department of Neurosurgery, First Affiliated Hospital of Xinjiang Medical University were selected. In addition, 12 patients with petroclival meningioma who had undergone microscopic surgery were used as control. Clinical data from the 24 cases of petroclival meningioma were analyzed. RESULTS: For the neuroendoscope-assisted group, six, five, and one cases were respectively subjected to total resection, subtotal resection, and most resection. For the microscopic surgery group, two, three, and seven cases were respectively subjected to total resection, subtotal resection, and most resection. Both the total and subtotal resection rates of petroclival meningioma in the neuroendoscope-assisted group were significantly higher than those in the microscopic surgery group (p < 0.05). No difference was observed for short-term and long-term complications (p > 0.05) between the two groups. CONCLUSION: Neuroendoscope-assisted microscopic resection for petroclival meningioma can improve the total and subtotal resection rates of the tumor. Moreover, this method does not increase postoperative short-term and long-term complications.