RESUMO
Objective:To investigate the asymmetric geometry of middle cerebral artery (MCA) bifurcations and aneurysm formation.Methods:From January 2017 to April 2020, 65 patients with MCA aneurysm underwent 3D-digital subtraction angiography (DSA) in our hospital were recruited in this study; 170 patients without arterial stenosis or cerebral aneurysm at the same time period were selected as normal control group; their corresponding morphological parameters of MCA bifurcations in the imaging data were analyzed. Bifurcation angle was termed as φ1, while small and large lateral angles were termed as φ2 and φ3, respectively. D2, S2, C2, T2 and E2 represented diameter, sectional area, circumference, tortuosity and ellipticity of the branch forming angle φ2 with parent vessel, respectively; whereas D3, S3, C3, T3 and E3 represented diameter, sectional area, circumference, tortuosity and ellipticity of the branch forming angle φ2 with parent vessel on the contralateral branch, respectively. The independent factors affecting the formation of MCA aneurysm were screened by binary Logistic regression, and the predictive value of independent factors affecting the formation of MCA aneurysm was evaluated by receiver operating characteristic (ROC) curve.Results:(1) The aneurysmal group had significantly larger φ1, significantly smaller φ2 and φ3 than the normal control group ( P<0.05); D3, S3, C3, T2, T3 and E2 in the aneurysmal group were significantly higher/larger than those in the normal control group ( P<0.05). In terms of the symmetry of bilateral branches of blood vessels, the difference of φ3/φ2 ratio between the normal control group and aneurysm group was statistically significant ( P<0.05). (2) Binary Logistic regression results showed that φ2 was the protective factor for aneurysm formation ( OR=0.880, 9 5%CI: 0.844-0.918, P=0.000), while D3 and φ3/φ2 ratio were the risk factors for aneurysm formation ( OR=4.493, 9 5%CI: 1.414-14.278, P=0.011; OR=30.676, 95%CI: 9.884-95.202, P=0.000). (3) The ROC curve showed that the area under the curve of φ2 was the largest, reaching 0.93, and the optimal cut-off point was 104.59°, enjoying sensitivity and specificity of 87.7% and 85.9%, respectively. Conclusion:Normal MCA bifurcations almost show symmetrical morphology, whereas aneurysmal MCA bifurcations show asymmetrical morphology in both lateral angles and daughter branches; φ2 is the best morphological parameter to predict the aneurysm formation of MCA bifurcations.
RESUMO
Estrogen Receptor (ERalpha) is a member of superfamily of ligand-activated transcription factors which play critical roles in many biological processes. To screen novel modulators of ERalpha for drug development and biological function research, we developed a mammalian one-hybrid-based high-throughput screening model for ERalpha modulator. We cloned the ERalpha LBD gene from the total mRNA of fat tissue by RT-PCR and fused it with the GAL4 DNA binding domain of pBIND-GAL4 plasmid to construct a chimara expression plasmid pBIND-GAL4-Eralpha(LBD). The L02 cells was cotransfected with pBIND-GAL4-ERalpha(LBD) and a GAL4-responsive luciferase reporter plasmid pGL3-GAL4, and following treatment with test compounds for 24 h, the activities of luciferase were detected to evaluate the transactivities of ERalpha modulators. After manner optimizations of transfection conditions, Estradiol, an agonist control, induced the expression of luciferase in a dose-dependent with EC50 of 0.17 micromol/L, the maximum folds of induction was about 28.1. Tamoxifen, an antagonist control, efficiently suppressed the estradiol-mediated luciferase induction with EC50 of 0.10 micromol/L. Using this screening model, we discovered four ERalpha agonists from 2000 natural and synthetic compounds.
