Advances in the study of KRAS in brain arteriovenous malformation.

Background：Brain arteriovenous malformation (bAVM) is an abnormal vascular mass with disordered arteriovenous connection. Endothelial KRAS mutation is common in bAVM. In vivo studies have demonstrated that mutations of KRAS in somatic cells can induce bAVM-like angiogenesis, suggesting that KRAS gene may play a key role in the development and progression of bAVM. Summary：In this article, we will provide a comprehensive review of action mechanisms of KRAS mutations in the development of bAVM and summarize potential targeting drugs for KRAS mutations in bAVM somatic cells. Key Message: KRAS mutation in human brain endothelial cells is a key driver in the pathogenesis of sporadic cerebral arteriovenous malformations. It is of great clinical importance to explore and summarize the changes in the signaling pathway induced by KRAS mutation, which may provide additional targets for the treatment of sporadic bAVM development.

Embolization of Cavernous Sinus Dural Arteriovenous Fistula with Liquid Materials Under Transarterial Balloon Protection.

AIM: To analyze the clinical and angiographic outcomes of interventional embolization under transarterial balloon protection technique in patients with cavernous sinus dural arteriovenous fistulas. MATERIAL AND METHODS: In a single-center cohort of 30 patients undergoing cavernous sinus dural arteriovenous fistulas embolization under balloon protection. We collected their clinical symptoms, complications, mid-term follow-up angiographic results, and long-term clinical outcomes for the baseline characteristics. RESULTS: Thirty patients with 31 lesions were included in this study. Immediate applications of angiographies after embolization indicated that complete obliteration occurred in 29 lesions (93.5% of 31 lesions). Two cases with permanent trigeminal nerve palsy were treated by arterial approach. Onyx dispersed into the internal carotid artery in one process, and salvage stent implantation was performed to prevent parent artery occlusion. CONCLUSION: Interventional embolization with intra-arterial balloon protection is effective and safe with rarely occurring complications.

Niche Differentiation of Biofilm Microorganisms in a Full-scale Municipal Drinking Water Distribution System in China and Their Implication for Biofilm Control.

Biofilms on the inner surface of a drinking water distribution system (DWDS) affect water quality and stability. Understanding the niche differentiation of biofilm microbial communities is necessary for the efficient control of DWDS biofilms. However, biofilm studies are difficult to conduct in the actual DWDS because of inaccessibility to the pipes buried underground. Taking the opportunity of infrastructure construction and relevant pipeline replacement in China, biofilms in a DWDS (a water main and its branch pipes) were collected in situ, followed by analysis on the abundances and community structures of bacterial and archaeal using quantitative PCR and high-throughput sequencing, respectively. Results showed that archaea were detected only in the biofilms of the water main, with a range of 9.4×103~1.1×105 copies/cm2. By contrast, bacteria were detected in the biofilms of branch pipes and the distal part of the water main, with a range of 8.8×103~9.6×106 copies/cm2. Among the biofilm samples, the archaeal community in the central part of the water main showed the highest richness and diversity. Nitrosopumilus was found to be predominant (86.22%) in the biofilms of the proximal part of the water main. However, Methanobrevibacter (87.15%) predominated in the distal part of the water main. The bacterial community of the water main and branch pipes was primarily composed of Firmicutes and Proteobacteria at the phylum level, respectively. Regardless of archaea or bacteria, only few operational taxonomic units (OTUs) (<0.5% of total OTUs) were shared by all the biofilms, indicating the niche differentiation of biofilm microorganisms. Moreover, the high Mn content in the biofilms of the distal sampling location (D3) in the water main was linked to the predominance of Bacillus. Functional gene prediction revealed that the proportion of infectious disease-related genes was 0.44-0.67% in the tested biofilms. Furthermore, functional genes related to the resistance of the bacterial community to disinfections and antibiotics were detected in all the samples, that is, glutathione metabolism-relating genes (0.14-0.65%) and beta-lactam resistance gene (0.01-0.05%). The results of this study indicate the ubiquity of archaea and bacteria in the biofilms of water main and branch pipes, respectively, and pipe diameters could be a major influencing factor on bacterial community structure. In the water main, the key finding was the predominant existence of archaea, particularly Nitrosopumilus and methanogen. Hence, their routine monitoring and probable influences on water quality in pipelines with large diameter should be given more attention. Besides, since Mn-related Bacillus and suspected pathogenic Enterococcus were detected in the biofilm, supplementation of disinfectant may be a feasible strategy for inhibiting their growth and ensuring water quality. In addition, the monitoring on their abundance variation could help to determine the frequency and methods of pipeline maintenance.

Use of 3D-printing cerebral aneurysm model assisting microcatheter shaping in neurovascular intervention technique training.

BACKGROUND: Microcatheter shaping plays a vital role in coil embolization of cerebral aneurysms, while the complicated method and insufficient training opportunities make it difficult for junior neurovascular clinicians to master this technique. In this program, we constructed a novel training method and assessment system for microcatheter shaping in coil embolization of cerebral aneurysms with 3D technique, and evaluated its efficacy for microcatheter shaping training in junior neurovascular clinicians. METHODS: Patient-specific models for cerebral aneurysms in different locations and with different morphologies were selected by experienced senior neurovascular clinicians. The solid polylactic acid model and the soft hollow crystal silicone model of intracranial aneurysms were then made separately for shaping reference and assessment in the training course. Twelve residents without prior experience of microcatheter shaping and 25 neurovascular clinicians who have in vivo experience of microcatheter shaping on 3-5 occasions were selected for this training program and randomly divided into the traditional training group and the experimental training group. Four senior neurovascular clinicians assisted and guided the trainees in two groups and evaluated the time and accuracy of microcatheter shaping. RESULTS: Eighteen trainees were assigned to the traditional training group, among which 4 had prior experience in microcatheter shaping. The other 19 were assigned to the experimental training group, including 8 with prior experience. No statistical difference in the distribution of experienced students between the two groups was noted(P = 0.295). After the training session, the shaping time was found shorter in the experimental training group than that in the traditional training group (40.3.5 ± 16.2 s vs. 54.2 ± 16.4 s, P = 0.014), while the shaping score was found higher in the experimental training group than that in the traditional training group (4.4 ± 0.5 vs. 2.6 ± 1.2, P < 0.001). Specifically, for the trainees without prior experience, the experimental training group also showed less time consumption and higher score (Time: 52.7 ± 7.7 vs. 61.5 ± 9.5, P = 0.02; Score 4.1 ± 0.5 vs. 2.3 ± 1.1, P < 0.01). Meanwhile, for the trainees with prior experience, the advantage was noted in shaping score (4.7 ± 0.3 vs. 3.9 ± 0.6, P < 0.01) but not in time consumption (23.3 ± 4.4 vs. 28.5 ± 3.9, P = 0.07). CONCLUSION: This training program is quite effective at teaching junior neurovascular physicians the essential surgical abilities required for coiling cerebral aneurysms.

Staged stenting strategy of acutely wide-neck ruptured intracranial aneurysms: A meta-analysis and systematic review.

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.

Identification of Prognostic Signature of Necroptosis-Related lncRNAs and Molecular Subtypes in Glioma.

Background: In tumor progression and epigenetic regulation, long non-coding RNA (lncRNA) and necroptosis are crucial regulators. However, in glioma microenvironment, the role of necroptosis-related lncRNAs (NRLs) remains unknown. Method: In this study, the RNA-seq and clinical annotation of glioma patients were analyzed using the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. To investigate prognosis and tumor microenvironment of NRLs in gliomas, we conducted a prediction model based on the training cohort. The accuracy of the model was verified in the verification cohort. Results: A signature composed of 13 NRLs was identified, and all glioma patients were divided into two groups. We found that each group has unique survival outcomes, biological behaviors, and immune infiltrating status. The necroptosis-related lncRNA signature (NRLS) model was found to be an independent risk factor in multivariate Cox analysis. Immunosuppressive microenvironment was positively correlated with the high-risk group. Due to significantly different IC50 between risk groups, NRLS could be used as a guide for chemotherapeutic treatment. Further, the entire cohort was divided into two clusters depending on NRLs. Consensus clustering method and the risk scoring system were basically similar. Survival probability was higher in Cluster 2, while Cluster 1 has stronger immunologic infiltration. Conclusion: The predictive signature could be a prognostic factor independently and serve to detect the role of NRLs in glioma immunotherapy response.

The 8-year single-center experience of telescoping flow diverter for complex intracranial aneurysms treatment.

OBJECTIVE: Treatment of complex intracranial aneurysms (IAs) is still a challenging thing and this study aims to summarize the experience of telescoping flow diverters (FDs) in treating complex intracranial aneurysms. METHOD: Between April 2013 to November 2020, 381 IA cases treated by flow diverters (FD) were retrieved from the database of 4988 IA cases, and finally 20 cases treated by telescoping FDs were enrolled for further analysis. RESULT: Among 20 patients, 15 patients (75.0%) received Tubridge telescoping while 5 patients (25.0%) received PED telescoping. The technical success rate was 100%. The immediate occlusion results were: 7 cases of OKM grade A (35.0%), 11 cases of OKM grade B (55.0%), and 2 cases of OKM grade C (10.0%). No perioperative complications occurred. The clinical follow-up was available in 20 patients (100%) and the follow-up time was 6-96 months. One patient developed massive infarction and the other 19 patients were range between 0 and 2. The angiographic follow-up was available in 17 patients (85%) and the follow-up time was 6-27 months. The occlusion results were: 1 case of OKM grade B (5.9%), 6 cases of OKM grade C (35, 0.3%), and 10 cases of OKM grade D (58.8%). 2 patients (11.8%) developed occlusion of the patent artery. CONCLUSION: Telescoping flow diverters showed low perioperative complications and high IA occlusion rate when treating complex intracranial aneurysms in follow-up time, which provides an alternative manner beyond conventional strategy for neurosurgeons.

Braided stents assisted coiling for endovascular management of posterior cerebral artery aneurysms: a preliminary mid-term experience.

PURPOSE: Posterior cerebral artery (PCA) aneurysms are rare. This study is to evaluate the preliminary experience of braided stents applied in PCA aneurysms treatment. METHODS: Angiographic and clinical data of 28 PCA patients treated with braided stents from July 2016 and September 2020 were retrospectively analyzed. RESULTS: A total of 28 PCA aneurysms were enrolled. 22 (78.6%) aneurysms were dissecting aneurysms, while 6 (21.4%) aneurysms were saccular aneurysms. Thirty-five braided stents were implanted with dual stents implanted in 7 cases. Immediate angiographic results show that Raymond class I was obtained in 13 patients (46.4%), Raymond class II was obtained in 4 patients (14.3%), and Raymond class III was obtained in 11 patients (39.3%). Perioperative hemorrhagic events occurred in 1 patient (3.6%). Twenty-four patients (85.7%) received angiographic follow-up, and the mean follow-up time was 11.2 ± 4.9 months. Two patients (8.3%) were confirmed with IA neck recurrence, and 3 patients (12.5%) were confirmed asymptomatic parent artery occlusion (PAO). The other 19 patients were confirmed promoted occlusion with 18 Raymond class I (75%) and 1 Raymond class II (4.2%). Twenty-seven patients (96.4%) received clinical follow-up, and the mean follow-up time was 32.2 ± 13.5 months. One patient (3.7%) confirmed the death event 2 weeks after discharge. The other 27 patients (96.3%) got favorable clinical outcomes with an mRS score of 0-2. CONCLUSIONS: Braided stent-assisted coiling with a high occlusion rate and relatively low complication rate provides an alternative strategy in treating PCA aneurysms. Long-term outcomes need further randomized study with larger case numbers.

Low-profile LEO baby stents using dual stenting technique in treating complex intracranial aneurysms located in small artery: Initial and mid-term outcome.

BACKGROUND: Endovascular treatment of complex intracranial aneurysms (IAs) was challenging. Our retrospective study aimed to assess the efficacy and safety of LEO Baby stents using the dual stenting technique for complex IAs. METHODS: Clinical and angiographic data of 15 IAs located in small arteries treated by LEO Baby stents in our neurosurgical center were retrospectively collected and analyzed between April 2019 to January 2021. RESULTS: 15 patients received dual stent-assisted coiling procedures and the stent configurations include 7 cases of T- configuration, 5 cases of parallel- configuration, 2 cases of Y- configuration, and 1case of X- configuration. 11 patients received dual stents deployment with only LEO Baby stents and 4 patients received LEO Baby stent combined with LVIS stent. Immediate postprocedural results showed Raymond I in 4 patients (26.7%), Raymond II in 5 patients (33.3%), and Raymond III in 6 patients (40.0%). One patient (6.7%) was confirmed with an ischemic complication during the procedure. All 15 patients (100%) received clinical follow-up ranging between 6 and 28 months. An mRS score of 0-2 was reached in all patients. 13 patients (86.7%) received angiographic clinical follow-up ranging between 6 and 20 months. The results revealed that Raymond I was achieved in 10 patients (76.9%) and Raymond II was achieved in 3 patients (23.1%). One patient (7.7%) in 6 months after the procedure was confirmed with asymptomatic in-stent stenosis. CONCLUSION: This preliminary study suggests that dual stents deployment of LEO Baby stents was a feasible strategy for the treatment of complex IAs located in the small arteries.

Flow diversion for aneurysms beyond the circle of Willis: A preliminary experience.

OBJECTIVE: To evaluate the safety and efficacy of flow diversion (FDs) for the aneurysms beyond the circle of Willis. METHODS AND MATERIALS: We retrospectively reviewed the prospectively maintained database in our center and enrolled patients with aneurysms beyond the circle of Willis (defined as at or distal to the M1, A2, and P2 segments) that were treated with FDs. RESULTS: Between July 2017 to December 2020, 28 patients with 28 aneurysms met the inclusion criteria and were included in this study, with a median age of 50 years old (IQR, 36-63 years). Thirty FDs, including 5 Pipelines and 25 Tubridge FDs, were deployed. Perioperative complications were noticed in 2 patients (7.1%), while asymptomatic adverse events occurred in another three patients (10.7%). Delayed complications occurred in 3.6% of patients (1/28). All patients received clinical follow-up, with the mortality and long-term morbidity of 0 and 3.6% (1/28), respectively. Angiographic follow-up data were available for 26 patients (92.9%) with an interval of 10 ± 7 months (ranged 2-26 months). Sixteen patients (61.5%) showed complete or nearly complete occlusion of aneurysms (OKM grading scale D and C); 6 cases (23.1%) were revealed incomplete occlusion (OKM grading scale B), and 4 cases (15.4%) remained unchanged (OKM grading scale A). The existence of the perforators derived from aneurysms was associated with a lower occlusion rate (p = 0.032). CONCLUSION: Flow diversion is reliable in the treatment of distal aneurysms with a high technical success rate and low permanent disability rate. The presence of side branches derived from aneurysms was associated with a lower aneurysm occlusion rate.

Epigenetic Regulation in Pathology of Atherosclerosis: A Novel Perspective.

Atherosclerosis, characterized by atherosclerotic plaques, is a complex pathological process that involves different cell types and can be seen as a chronic inflammatory disease. In the advanced stage, the ruptured atherosclerotic plaque can induce deadly accidents including ischemic stroke and myocardial infarction. Epigenetics regulation, including DNA methylation, histone modification, and non-coding RNA modification. maintains cellular identity via affecting the cellular transcriptome. The epigenetic modification process, mediating by epigenetic enzymes, is dynamic under various stimuli, which can be reversely altered. Recently, numerous studies have evidenced the close relationship between atherosclerosis and epigenetic regulations in atherosclerosis, providing us with a novel perspective in researching mechanisms and finding novel therapeutic targets of this serious disease. Here, we critically review the recent discoveries between epigenetic regulation mechanisms in atherosclerosis.