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 evaluate the the effect of two blood purification in patients with chronic renal failure uremia. Methods: One hundred cases of patients from April 2012 to February 2014 in our hospital were chosen as the experimental object, and were divided into experimental group and control group, control group were treated with hemodiafiltration, and the experimental group were treated with high-flux hemodialysis,the serum medium and small molecule toxins and cognitive function improvement were compared. Results:The serum medium and small molecule toxins and cognitive function of two group were greatly improved, there were significant differences(t=4.113, t=0.430, t=1.038, t=0.346; P<0.05).The experimental group after treatment, serum phosphorus, parathyroid hormone was lower than the control group, the difference was statistically significant (t=-4.189, t=4.113;P<0.05). The experimental group PL and Amp were better than the patients in the control group, the difference was statistically significant (t=15.023, t=3.428; P<0.05). Conclusion: Two blood purification has good effect on treating patients with chronic renal failure uremia, but the improving effect of high flux hemodialysis scavenging effect on cysC, parathyroid hormone and serum phosphorus and cognitive function are better than that of hemodiafiltration.

Objective:To report and analyze a rare family of sponduloepiphyseal dysplasia congenital(SEDC) in order to supply more resources for genetic bone disease. Methods:Investigation and analysis was performed on a four generation's family of SEDC.Clinic characteristics including X-ray image and chromosome analysis were evaluated.Results:Nine persons suffered from SEDC in this four(generation's) family.The patients presented with same clinical characteristics.The main bone damages affected vertebrae,articulatio coxae,caput femoris and neck. Conclusion:The mode of inheritance of SEDC may be autosomal dominant inheritance.Gene defect during embryonic period may interfere the growth of osteoepiphysis.Further molecular pathologic studies were needed to find the evidence of genetic prognostication of SEDC.

Objective To dissect the molecular mechanism of toxic neuropathy induced by allyl chloride (AC).Methods Fluorescence molecular probe (Fura-2/AM), electron probe X-ray microprobe analysis (EPMA) and biochemical methods were used to determine the concentrations of cytosolic free Ca2+, the contents of intracellular Ca2+ percentage, Ca2+-free calmodulin(CaM), the activity of Ca2+/CaM-dependent protein kinase Ⅱ (Ca2+/CaM-PK Ⅱ), and cytoskeletal protein synthesis in chicken embryo brain cells induced by AC. Results The contents of Ca2+ percentage, the concentrations of cytosolic free Ca2+, and the activities of Ca2+/CaM-PK Ⅱ in the cells were increased significantly as AC was added (P<0.01). However, the content of Ca2+-free CaM and the synthesis of cytoskeletal proteins were markedly decreased (P<0.01).Conclusion The results suggest that one of the mechanism of AC-induced cytoskeletal injury in vitro might be related to the elevation of intracellular Ca2+, activated CaM and Ca2+/CaM-PK Ⅱ.