Effects of Coronary Artery Lesion Characteristics on Myocardial Ischemia / 医用生物力学

Objective To investigated the effect of stenosis characteristics (vascular elasticity and plaque properties) on myocardial ischemia. Methods An ideal geometric multi-scale coronary stenosis model based on fluid-structure interaction was established, and the fractional flow reserve (FFR) was simulated to evaluate myocardial ischemia. The effects of vascular elastic wall (elastic modulus of 1 MPa) and rigid wall, plaque types (lipid-rich plaque and calcified plaque) and plaque volume on myocardial ischemia were considered separately. Results The FFRCT simulation result of vessels with elastic wall was larger than that with rigid wall under all stenosis situations. The FFRCT of vessels in lipid-rich lesions was higher than that of calcified plaque (P=0.001). The trapezoidal plaque volume was larger than the cosine plaque volume, and the FFRCT of vessels in trapezoidal plaque was smaller than that of cosine plaque (P=0.001). Conclusions Vascular elasticity is a critical factor to simulate vascular hemodynamics. In moderate stenosis, calcified plaques are more likely to induce myocardial ischemia due to the larger luminal deformation and dilation of rich lipid plaque. When the stenosis is constant, the smaller the plaque volume, the higher the FFRCT and the smaller the possibility of myocardial ischemia.

Target binding and residence: a new determinant of DNA double-strand break repair pathway choice in CRISPR/Cas9 genome editing / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is widely used for targeted genomic and epigenomic modifications and imaging in cells and organisms, and holds tremendous promise in clinical applications. The efficiency and accuracy of the technology are partly determined by the target binding affinity and residence time of Cas9-single-guide RNA (sgRNA) at a given site. However, little attention has been paid to the effect of target binding affinity and residence duration on the repair of Cas9-induced DNA double-strand breaks (DSBs). We propose that the choice of DSB repair pathway may be altered by variation in the binding affinity and residence duration of Cas9-sgRNA at the cleaved target, contributing to significantly heterogeneous mutations in CRISPR/Cas9 genome editing. Here, we discuss the effect of Cas9-sgRNA target binding and residence on the choice of DSB repair pathway in CRISPR/Cas9 genome editing, and the opportunity this presents to optimize Cas9-based technology.