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 describe an appreciate operation method in the treatment of deformi-ties secondary to gluteal muscles and fascia contracture. Methods 25 cases of serious secondary de-formity of gluteal muscles and fascia contracture were treated by Z-plasty. The contracted fascia and scar were loosed and the skin around the wound was rearranged. Results The following-up time was from 6 months to 3 years with an average time of 1.6 years. All cases rehabilitated to normal or nearly normal in gait. Aesthetic results were also satisfactory. No recurrence was observed. Conclusion Re-arranging the contracted fascia with Z-plasty can extend the fascia and improve the movement of the hip joint. Besides, Z-plasty treatment of skin around the scar is benefit for the aesthetic result of the deformities, Z-plasty of contracted fascia and skin is an appreciate operation method in the treatment of deformities secondary to gluteal muscles and fascia contracture.

OBJECTIVEThe purpose of this study is to comprehensively explore the risk factors of primary open angle glaucoma (POAG) in China.

METHODSTwo groups of data based on distinct resources were analyzed to explore the risk factors of POAG. One group of data was based on hospital records between 1995 and 2000 which composed of 107 patients with POAG and 149 controls without POAG. The other group of data was based on 40 patients with POAG and 120 matched controls without POAG. The former was designed by non-matched case control study, the latter was done by 1:3 matched case control study. The relationships between POAG and the factors such as age, sex, family history, diabetes, hypertension, intraocular pressure (IOP), cardiovascular diseases, smoking, drinking and mutation of TIGR gene were studied by logistic regression analysis.

RESULTSThe simple factor analysis showed that the risk of POAG was related to age, family history, hypertension, IOP, cardiovascular diseases, smoking, drinking and the mutation of TIGR gene (T353I). However, logistic regression analysis confirmed that POAG mainly related to IOP, family history, hypertension, smoking, alcohol intake and the mutation of TIGR gene.

CONCLUSIONThe most important risk factor of POAG was IOP. Family history, hypertension, smoking and the mutation of TIGR gene were also important risk factors of POAG. However, alcohol intake was a protective factor for POAG.

Adolescent ; Adult ; Age Factors ; Aged ; Alcohol Drinking ; adverse effects ; Case-Control Studies ; China ; epidemiology ; Cytoskeletal Proteins ; Eye Proteins ; genetics ; Female ; Glaucoma, Open-Angle ; epidemiology ; genetics ; Glycoproteins ; genetics ; Humans ; Male ; Middle Aged ; Risk Factors ; Smoking ; adverse effects