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Basilar artery trunk aneurysms (BTAs) are relatively rare, with poor natural prognosis, high disability and mortality rates. The treatment options for BTAs includes conservative treatment, craniotomy, and endovascular treatment. Due to the deep anatomical structure, rich perforating vessels, and complex pathological structure of the basilar artery, craniotomy is more difficult. There is currently no consensus on the treatment of BTAs. This article reviews the current treatment status of BTAs, aiming to provide reference for clinical work.
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Background@#Xylazole (Xyl) is a veterinary anesthetic that is structurally and functionally similar to xylazine. However, the effects of Xyl in vitro remain unknown. @*Objectives@#This study aimed to investigate the anesthetic mechanism of Xyl using fetal rat nerve cells treated with Xyl. @*Methods@#Fetal rat nerve cells cultured for seven days were treated with 10, 20, 30, and 40 μg/ mL Xyl for 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, and 120 min. Variations of amino acid neurotransmitters (AANTs), Nitric oxide-Cyclic GMP (NO-cGMP) signaling pathway, and ATPase were evaluated. @*Results@#Xyl decreased the levels of cGMP and NO in nerve cells. Furthermore, Xyl affected the AANT content and Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase activity in nerve cells. These findings suggested that Xyl inhibited the NO-cGMP signaling pathway in nerve cells in vitro. @*Conclusions@#This study provided new evidence that the anesthetic and analgesic effects of Xyl are related to the inhibition of the NO-cGMP signaling pathway.
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The ongoing SARS-CoV-2 pandemic has brought an urgent need for animal models to study the pathogenicity of the virus. Herein, we generated and characterized a novel mouse-adapted SARS-CoV-2 strain, named MASCp36, that causes severe acute respiratory symptoms and mortality in standard laboratory mice. Particularly, this model exhibits age and gender related skewed distribution of mortality akin to severe COVID-19, and the 50% lethal dose (LD50) of MASCp36 was 58 PFU in 9-month-old, male BALB/c mice. Deep sequencing identified three amino acid substitutions, N501Y, Q493H, and K417N, subsequently emerged at the receptor binding domain (RBD) of MASCp36, during in vivo passaging. All three mutations in RBD significantly enhanced the binding affinity to its endogenous receptor, mouse ACE2 (mACE2). Cryo-electron microscopy (cryo-EM) analysis of human ACE2 (hACE2) or mACE2 in complex with the RBD of MASCp36 at 3.1 to 3.7 angstrom resolution elucidates molecular basis for the receptor-binding switch driven by specific amino acid substitutions. Interestingly, N501Y and Q493H enhanced the binding affinity to human ACE2 (hACE2); while triple mutations N501Y/Q493H/K417N decreased affinity to hACE2, thus led to the reduced infectivity of MASCp36 to human cells. Our study not only provides a robust platform for studying the pathogenesis of severe COVID-19 and rapid evaluation of coutermeasures against SARS-CoV-2, but also unveils the molecular mechanism for the rapid adaption and evolution of SARS-CoV-2 in human and animals. One sentence summaryA mouse adapted SARS-CoV-2 strain that harbored specific amino acid substitutions in the RBD of S protein showed 100% mortality in aged, male BALB/c mice.
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Purpose@#Fractionated radiotherapy as well as concomitant and adjuvant chemotherapy such astemozolomide for postoperative high-grade glioma (HGG) patients improves progressionfreesurvival and overall survival. Multiple factors such as chemotherapy, radiotherapy,tumor grade, residual tumor volume, and genetic modifications might play a role in the formationof cognitive impairment. The risk factors of cognitive impairment in postoperativepatients with HGG receiving radiotherapy and chemotherapy remains a concern in this population.The purpose of this study was to identify risk factors for cognitive impairment inpatients of postoperative HGG. @*Materials and Methods@#A total of 229 patients with HGG who underwent surgery were analyzed. Cognitive impairmentwas defined as a decrease of Cognitive Assessment Montreal (MoCA)’s score in atleast two cognitive domains or any MoCA’s score of less than 26 points at the time of studycompared with baseline level. Multiple potential risk factors including methylated status ofthe O6-methylguanine-DNA methyltransferase (MGMT) promoter, glioma World HealthOrganization (WHO) grade, residual tumor volume, education, and sex were analyzed. Coxunivariate and multivariate regression analysis was used to detect the significant risk factorsfor cognitive impairment. @*Results@#At the end of follow-up among the 229 patients, 147 patients (67%) developed cognitiveimpairment. 82 patients (36%) remained in normal cognitive condition. In multivariate analysis,unmethylated MGMT promoter (hazard ratio [HR], 1.679; 95% confidence interval [CI],1.212 to 2.326; p=0.002), glioblastoma (HR, 1.550; 95% CI, 1.117 to 2.149; p=0.009),and residual tumor volume > 5.58 cm3 (HR, 1.454; 95% CI, 1.047 to 2.020; p=0.026) wereindependent risk factors for cognitive impairment. @*Conclusion@#Methylated status of the MGMT promoter, glioma WHO grade, and residual tumor volumemight be risk factors for the cognitive impairment in postoperative patients with HGG.