Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Objective To explore the clinical application of percutaneous puncture and drainage in treating pyogenic liver abscess. Methods A total of 30 patients with pyogenic liver abscess were treated with ultrasound-guided percutaneous puncture and aspiration of abscess cavity , which was followed by DSA-guided drainage tube placement together with proper washing of abscess cavity. Results Puncturing and flushing of abscess cavity was performed in two patients with < 4 cm liver abscess , and tube placement as well as drainage was carried out in the other 28 patients with > 4 cm liver abscess. No severe complications occurred. Complete cure was obtained in all the 26 patients who had no malignant tumors. Of the 4 patients with malignant tumor, cure obtained in one and death occurred in three. Conclusion Ultrasound-guided or DSA-guided percutaneous puncture and drainage therapy is technically simple, less invasive, highly safe and clinically effective treatment for pyogenic liver abscess.