This study is designed to obtain recombinant human acetylcholinesterase (rhAChE) and apply it in screening acetylcholinesterase inhibitors. The rhAChE was overexpressed in HEK293 cells transfected by plasmid of pCMV-AChE with the cationic liposome and rhAChE was found to be secreted into cell culture medium. AChE activity was assayed according to modified Ellman method to obtain kinetic parameters. IC so50 values for donepezil compounds of rhAChE were calculated to determine their activities of inhibition. The results showed that Km value was 151.9 micromol.L-1 donepezil inhibited rhAChE in a mixed competitive-noncompetitive way (Ki= 16.03 nmol.L-1, Ki = 18.36 nmol.L-1) and that most new compounds tested exhibited high activities of inhibition on rhAChE. The study suggests that rhAChE is available to be applied in screening AChE inhibitors in vitro.

Objective To analyze the change trend of hospitalized patients with pulmonary embolism in Wuzhou city during 2004-2014,and analysis of its risk factors.Methods From January 2004 to January 2014,from four comprehensive tertiary hospitals of Wuzhou city,we selected hospitalized cases of pulmonary embolism as investigation subjects,which from 2004 to 2008 were selected as control group,and from January 2009 to January 2014 were selected as observation group.The hospitalization rate,mortality rate and risk factors were compared between the two groups.Results From 2004 to 2008,there were 257 370 cases of hospitalized,pulmonary embolism hospitalized in 52 cases at the same period,accounting for 0.02％ of the total hospitalized cases.From January 2009 to January 2014,there were 367 728 cases of hospitalized,pulmonary embolism hospitalized in 115 cases at the same period,accounting for 0.03％ of the total hospitalized cases.The proportion of pulmonary embolism in total hospitalization between the two groups had statistically significant difference (P ＜ 0.05).From 2004 to 2008,in 52 cases of pulmonary embolism,24 cases (46.15％) died,includef 16 cases(30.7％) died of pulmonary embolism,and the rest 8 cases(15.38％) died of the complication.From 2009 to 2014,in 115 cases of pulmonary embolism,30 cases (26.08％) died,included 23 cases(20.00％) died of pulmonary embolism,and the rest 7 cases(6.08％) died of complications.The difference of the mortality rate in the two periods was statistically significant (x2 =3.879,P ＜ 0.05).52 cases of pulmonary embolism of the control group were selected to study risk factors and basic diseases,the risk factors and basic diseases of pulmonary embolism had 11 kinds,the highest frequency was in lower limb venous thrombosis,followed by surgery and lie in bed for a long time,again for malignant tumor,smoking,fracture,hyperlipidemia,arrhythmia(atrial fibrillation,etc.) and diabetes,etc.Conclusion The hospitalization proportion and mortality trend of hospitalized patients with pulmonary embolism in Wuzhou city remains unchanged,to study the risk factors in order to get a better prevention and treatment measures.

Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.
Humans ; Signal Transduction ; Stomach Neoplasms/drug therapy* ; Reactive Oxygen Species/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2 ; Cell Line, Tumor