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Genome-wide association studies (GWAS) have become increasingly popular for detecting numerous loci associated with intracranial aneurysm (IA), but how these loci function remains unclear. In this study, we employed an integrative analytical pipeline to efficiently transform genetic associations and identify novel genes for IA. Using multidimensional high-throughput data, we integrated proteome-wide association studies (PWAS), transcriptome-wide association studies (TWAS), Mendelian randomization (MR) and Bayesian co-localization analyses to prioritize genes that can increase IA risk by altering their expression and protein abundances in the brain and blood. Moreover, single-cell RNA sequencing (scRNA-seq) of the circle of Willis was performed to enrich filtered genes in cells, and gene set enrichment analysis (GSEA) was conducted for each gene using bulk RNA-seq data for IA. No significant genes with cis-regulated plasma protein levels were proven to be associated with IA. The protein abundances of five genes in the brain were found to be associated with IA. According to cellular enrichment analysis, these five genes were expressed mainly in the endothelium, fibroblasts and vascular smooth muscle cells. Only three genes, CNNM2, GPRIN3 and UFL1, passed MR and Bayesian co-localization analyses. While UFL1 was not validated in confirmation PWAS as it was not profiled, it was validated in TWAS. GSEA suggested these three genes are associated with the cell cycle. In addition, the protein abundance of CNNM2 was found to be associated with IA rupture (based on PWAS, MR and co-localization analyses). Our findings indicated that CNNM2, GPRIN3 and UFL1 (CNNM2 correlated with IA rupture) are potential IA risk genes that may provide a broad hint for future research on possible mechanisms and therapeutic targets for IA.
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INTRODUCTION: The case fatality rate among patients with aneurysmal subarachnoid hemorrhage (aSAH) has decreased progressively, with numerous patients subjected to contemporary paradigms that minimize the use of agonizing therapeutic processes. The concept of the "Textbook Outcome" (TO), a composite outcome that highlights numerous favorable outcomes, was developed in the context of gastrointestinal tumor surgeries and expeditiously extended across diverse surgical spheres. The aim of this study was to explore the factors hindering the achievement of optimal prognoses in postinterventional aSAH patients, employ textbook outcomes, and establish predictive models. METHODS: We conducted a retrospective review of data from 1270 aSAH patients who received endovascular treatment between 2012 and 2018. We delineated an exemplary TO within the aSAH domain, characterized by favorable clinical results, minimal complications, and the absence of retreatments. This TO-oriented approach is explained within the manuscript. RESULTS: The findings revealed that preoperative intraventricular hemorrhage (IVH), preoperative Hunt and Hess grade (H&H) ≥ 3, World Federation of Neurosurgical Societies (WFNS) grade ≥ 3, the presence of blebs on the aneurysm, aneurysms situated at branching sites, and non-stent-assisted endovascular intervention were the strongest risk factors for not achieving textbook outcomes (non-"Textbook Outcome" [N-TO]). Decision curve analysis and calibration analyses revealed strong concordance between the predictions of the N-TO nomogram model and the actual observations. CONCLUSIONS: Treatment Outcomes hold significant practical value in clinical studies of aSAH patients receiving endovascular treatment. The likelihood of N-TOs was predicted by IVH, H&H grade ≥ 3, WFNS grade ≥ 2, presence o f bleb on the aneurysm, and aneurysms located at branching sites.
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Intracranial aneurysms (IAs) are characterized by abnormal dilatation of the cerebral vessels. Vascular smooth muscle cells (VSMCs) are implicated in maintaining vascular homeostasis. Disordered VSMCs are one of the most common causes for occurrence and development of IAs. The bone morphogenetic protein 4 (BMP4) signalling pathway is involved in regulating cell proliferation, apoptosis, and differentiation. This study aimed to investigate the effects of BMP4 on VSMCs and its underlying mechanisms. BMP4 was upregulated in the VSMCs of IAs and caused apoptosis of VSMCs through Smad1/5 phosphorylation. In addition, BMP4 overexpression significantly promoted the proliferation and migration of VSMCs and induced a phenotypic transformation from contractile to inflammatory. Our findings facilitate further understanding of the occurrence and development of IAs and provide a potential therapeutic target.
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Aneurisma Intracraneal , Músculo Liso Vascular , Humanos , Proteína Morfogenética Ósea 4/genética , Proteína Morfogenética Ósea 4/metabolismo , Proteína Morfogenética Ósea 4/farmacología , Músculo Liso Vascular/metabolismo , Aneurisma Intracraneal/metabolismo , Transducción de Señal , Proliferación Celular , Miocitos del Músculo Liso/metabolismo , Células CultivadasRESUMEN
Background: Application of stent-assisted coiling and FD in acute phase of ruptured wide-necked aneurysms is relatively contraindicated due to the potential risk of ischemic and hemorrhagic complications. Scheduled stenting after initial coiling has emerged as an alternative paradigm for ruptured wide-necked aneurysms. The objective of this study is to evaluate the safety and efficacy of a strategy of staged stent-assisted coiling in acutely ruptured saccular wide-necked intracranial aneurysms compared with conventional early stent-assisted coiling strategy via propensity score matching in a high-volume center. Methods: A retrospective review of patients with acutely ruptured saccular wide-necked intracranial aneurysms who underwent staged stent-assisted coiling or conventional stent-assisted coiling from November 2014 to November 2019 was performed. Perioperative procedure-related complications and clinical and angiographic follow-up outcomes were compared. Results: A total of 69 patients with staged stent-assisted coiling and 138 patients with conventional stent-assisted coiling were enrolled after 1:2 propensity score matching. The median interval time between previous coiling and later stenting was 4.0 weeks (range 3.5-7.5 weeks). No rebleeding occurred during the intervals. The rate of immediate complete occlusion was lower with initial coiling before scheduled stenting than with conventional stent-assisted coiling (21.7 vs. 60.9%), whereas comparable results were observed at follow-up (82.5 vs. 72.9%; p = 0.357). The clinical follow-up outcomes, overall procedure-related complications and procedure-related mortality between the two groups demonstrated no significant differences (P = 0.232, P = 0.089, P = 0.537, respectively). Multivariate analysis showed that modified Fisher grades (OR = 2.120, P = 0.041) were independent predictors for overall procedure-related complications and no significant predictors for hemorrhagic and ischemic complications. Conclusions: Staged stent-assisted coiling is a safe and effective treatment strategy for acutely ruptured saccular wide-necked intracranial aneurysms, with comparable complete occlusion rates, recurrence rates at follow-up and overall procedure-related complication rates compared with conventional stent-assisted coiling strategy. Staged stent-assisted coiling could be an alternative treatment option for selected ruptured intracranial aneurysms in the future.
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Objective: In the study, we explored the safety and effectiveness of staged stenting strategy for acutely wide-neck ruptured intracranial aneurysms. Methods: Online databases, including PubMed, EMBASE, the Cochrane database, and Web of Science, were retrospectively and systematically searched. The main observation indicators were the procedure-related complication rate, complete occlusion rate, and favorable clinical outcome. Meta-analysis was performed using a random or fixed effect model based on heterogeneity. Results: A total of 5 studies with 143 patients were included. The hemorrhagic complication rate of the initial coiling and staged stenting was 2.8% (4 of 143) and 0, respectively. The ischemic complication rate of the coiling and supplemental stenting was 3.5% (5 of 143) and 2.9% (4 of 139), respectively. There were no deaths due to procedure-related complications in two stages. The aneurysm complete occlusion rate was 25% (95% CI, 0.13-0.03; I2 = 4.4%; P = 0.168) after initial coiling, 54% (95% CI, 0.63-0.64; I2 = 0%; P = 0.872) after staged stenting, and 74% (95% CI, 0.66-0.81; I2 = 56.4%; P = 0.562) at follow-up, respectively. Favorable clinical outcome rate 74% (95% CI, 0.61-0.86; I2 = 50.5%; P = 0.133) after discharge of initial coiling treatment, and 86% (95% CI, 0.80-0.92; I2 = 0; P = 0.410) after discharge from stenting, and 97% (95% CI, 0.93-1.01; I2 = 43.8%; P = 0.130) at follow-up. Conclusion: Staged stenting treatment of wide-neck RIA with coiling in the acute phase followed by delayed regular stent or flow-diverter stent had high aneurysm occlusion rate, favorable clinical outcome rate and low procedure-related complication rate. A more dedicated and well-designed controlled study is warranted for further evaluation of staged stenting treatment compared to SCA in wide-neck RIA.
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BACKGROUND: Chronic subdural hematoma (CSDH) is a common disease that forms between the dura and arachnoid membranes of the brain. With the development of medications and surgery, significant progress has been made in the diagnosis and treatment of CSDH. However, there is no comprehensive analysis available on CSDH-related studies published in the literature. This study aimed to collect and analyze CSDH-related studies published since the twenty-first century using bibliometric analysis and to summarize the current status of research in this field for the sake of providing systematic data for further study of CSDH. METHODS: CSDH-related studies were searched in the Web of Science Core Collection (WoSCC) database using the Medical Subject Heading (MeSH) term 'chronic subdural hematoma'. Data analysis and visualization were performed by R and CiteSpace software. RESULTS: This study retrieved 1424 CSDH-related articles published since the beginning of the twenty-first century. There was a general increase in both the number of published articles and the mean number of citations. The authors, institutions and journals that contributed the most to the field of CSDH were Jianning Zhang, Tianjin Medical University, and world neurosurgery, respectively. The reference co-citation network identified 13 clusters with significant modularity Q scores and silhouette scores (Q = 0.7124, S = 0.8536). The major research categories were (1) evolution of the therapeutic method and (2) the etiology and pathology of CSDH. Keyword analysis revealed that 'middle meningeal artery embolization' was the latest burst keyword. CONCLUSIONS: This study identified the most influential countries, authors, institutions and journals contributing to CSDH research and discussed the hotspots and the latest subjects of CSDH research.
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Embolización Terapéutica , Hematoma Subdural Crónico , Humanos , Embolización Terapéutica/métodos , Hematoma Subdural Crónico/cirugía , Arterias Meníngeas , Procedimientos Neuroquirúrgicos , BibliometríaRESUMEN
Objective: This study aims to compare the safety and efficacy of stent-assisted coiling (SAC) with those of coiling alone (CA) for the treatment of ruptured tiny intracranial aneurysms. Methods: We enrolled 245 patients with ruptured tiny intracranial aneurysms treated with coil embolization. Patients were grouped into SAC and CA groups. Baseline characteristics, periprocedural complications, clinical outcomes, and angiographic results were compared between the two groups. In addition, a subgroup analysis was conducted in the SAC group, and patients were regrouped into low-profile visualized intraluminal support (LVIS) and laser-cut groups to compare the perioperative procedure-related complications and clinical and angiographic follow-up outcomes. Results: All baseline characteristics were equivalent between the two groups except for aneurysm size and dome-to-neck aspect ratio. The rates of overall procedure-related complications, intraprocedural rupture, postoperative early rebleeding, intraprocedural thrombosis, postprocedural thrombosis, and procedure-related mortality were comparable between the two groups (P = 0.105, 0.145, 0.308, 1.000, 1.000, 0.160, respectively). Nevertheless, the rate of hemorrhagic complication in the SAC group was significantly higher (P = 0.023). The angiographic follow-up outcomes showed that the SAC group had a higher complete occlusion rate and lower recurrence rate (88.2 vs. 67.1%, 5.4 vs. 15.2%, P = 0.001). The clinical outcomes at discharge and follow-up between the two groups demonstrated no significant differences (P = 0.192 and P = 0.085, respectively). For subgroup analysis, LVIS stents were associated with a significantly higher rate of complete occlusion (P = 0.014) and a lower rate of intraprocedural rupture (p = 0.021). Moreover, multivariate analysis showed that there were no predictors for the overall, hemorrhagic, and ischemic procedure-related complications, while Raymond class was an independent predictor of retreatment (OR = 3.508, 95% CI 1.168-11.603; P = 0.029). Conclusion: Stent-assisted coiling may increase the incidence of hemorrhagic events with favorable angiographic results and comparable clinical outcomes compared with stand-alone coiling. Nevertheless, LVIS stent could improve the safety compared with lazer-cut stent. Simultaneously, considering the better long-term effect, LVIS stent-assisted coiling may be a preferable choice for ruptured tiny intracranial aneurysms.
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Background: Stenting is a common clinical practice to treat acutely ruptured intracranial aneurysm (RIA). Although multiple studies have demonstrated its long-term safety and effectiveness, there is currently a lack of bibliometric analysis on stent application in acutely RIA. This study sought to summarize the current status of research in this field and lay a foundation for further study. Materials and methods: Related publications were searched in the Web of Science Core Collection (WoSCC) database. Data analysis and visualization were performed by R and CiteSpace software. Results: A total of 275 publications published in English from 1997 to 2022 were included in this study. The growth of publications slowed down. The reference co-citation network identified 13 clusters with a significant network (Q = 0.7692) and convincing clustering (S = 0.9082). The research focus was acutely RIA and the application of stents during interventional procedures. The main trends of research were: (1) development of materials, and (2) safety of stent application in acutely RIA. The United States contributed the most articles, and Jianmin Liu was the most prolific author. Mayo Clinic was the leading institution in this field. Most articles were published in Interventional Neuroradiology. Conclusions: This study analyzed the research trends, hotspots and frontiers of stent application in acutely RIA. It is our hope that the results obtained could provide useful information to researchers to get a clearer picture about their future research directions in this field.
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Vacuum induction melting gas atomization (VIGA) has evolved as an important production technique of superalloy powders used in additive manufacturing. However, the development of powder preparation techniques is limited because the crushing process of gas-atomized metal melt is difficult to characterize by conventional experimental methods. Herein, we report the application of computational fluid dynamics to simulate the breaking behavior of droplets in the process of preparing nickel-based superalloy powders by VIGA, as well as the results on the effect of gas pressure on the atomization process and powder particle size distribution of metal melt. In the process of primary atomization, the crushing morphology of superalloy melt shows an alternate transformation of umbrella shapes and inverted mushroom cloud shapes, and with the increase in atomization pressure, the disorder of the two-phase flow field increases, which is conducive to sufficient breakage of the melt. Most importantly, in the process of secondary atomization and with the increasing atomization pressure, the particle size distribution becomes narrower, the median particle diameter and average particle size decrease, and the decreasing trend of the particle size increases gradually. The simulation results are compliant with the performed nickel-based superalloy powder preparation tests. This study provides insight into the production and process optimization of superalloy powder prepared by the VIGA method.
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The lattice structure was prepared by selective laser melting of 316L metal powder, and the epoxy was naturally infiltrated into the pores of the 316L metallic lattice structure. The epoxy/316L metallic lattice composites with integrated structure and function were prepared. Scanning electron microscopy was used to observe the microstructure of the epoxy/316L metallic lattice composites. The damping performance of the epoxy/316L metallic lattice composites were studied by modal measurement method. At the same time, the engineering stress-strain curve was obtained by a quasi-static compression experiment on a universal testing machine. The results show that the interface of epoxy and 316L metallic lattice is well bonded, and there are a few bubbles in the epoxy. The epoxy/316L metallic lattice composites have high damping characteristics with damping ratio over 10%. The energy absorption of epoxy/316L metallic lattice composites is as high as 68.32 MJ/m3, showing high energy absorption characteristics.
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The effects of nanosecond laser peening on Zr41Ti14Cu12.5Ni10Be22.5 metallic glass were investigated in this study. The peening treatment produced an extra-deep shock-affected zone compared to crystal metal. As opposed to the conventional shear bands, numerous arc shear bands appeared and aggregated in the vertical direction of the laser beam, forming basic units for accommodating plastic deformation. The arc shear bands exhibited short and discrete features near the surface of the material, then grew longer and fewer at deeper peened layer depths, which was closely related to the laser shock wave attenuation. An energy dissipation model was established based on Hugoniot Elastic Limit and shear band characteristics to represent the formation of an extra-deep shock-affected zone. The results presented here suggest that the bulk modification of metallic glass with a considerable affected depth is feasible. Further, they reveal that nanosecond laser peening is promising as an effective approach to tuning shear bands for improved MGs ductility.