OBJECTIVE To investigate the improvement mechanism of Huatan tongmai decoction on rats with polycystic ovary syndrome （PCOS） by regulating autophagy through phosphatidylinositol-3-kinase（PI3K）/protein kinase B（AKT）/mammalian target of rapamycin （mTOR） pathway. METHODS A total of 40 rats were randomly divided into blank group （purified water）， model group （purified water）， traditional Chinese medicine group [Huatan tongmai decoction， 24 g/（kg·d）] and chemical drug group [metformin， 0.16 g/（kg·d）]， with 10 rats in each group. Except for blank group， other groups were given a combination of high-fat diet and intragastric administration of 1 mg/kg letrozole suspension to establish PCOS rat model. After modeling， they were given relevant medicine or water intragastrically， once a day， for 42 consecutive days. After the last administration， the pathological and ultrastructural changes of ovarian tissue were observed. The levels of follicle stimulating hormone （FSH）， testosterone （T）， estradiol （E2） ，luteinizing hormone （LH） in serum were detected，and the LH/FSH ratio was calculated. mRNA expressions of Beclin-1， p62 and microtubule-associated protein 1 light chain 3 （LC3） in ovarian tissue were detected. The expressions of related proteins of PI3K/AKT/mTOR pathway and autophagy in rat ovarian tissues were also detected. RESULTS Compared with blank group， the pathological damage and ultrastructural changes of the ovarian tissue in the model group rats were obvious， and a large number of autophagosomes could be seen in cells. The levels of T and LH and the LH/FSH ratio in serum， as well as mRNA and protein expressions of Beclin-1 and LC3， were increased significantly （P＜0.05）， while the levels of E2 and FSH in serum， as well as mRNA and protein expressions of p62 and the phosphorylation levels of PI3K， AKT and mTOR proteins in ovarian tissue， were significantly decreased （P＜0.05）. Compared with model group， the pathological damage of ovarian tissue in the administration groups was significantly reduced， the number of autophagosomes was smaller， and the expression levels of the above indicators were significantly reversed （P＜0.05）. CONCLUSIONS Huatan tongmai decoction can inhibit autophagy in ovarian granular cells by activating the PI3K/AKT/mTOR pathway， regulate the secretion of sex hormones， alleviate pathological damage in ovarian tissues， and promote normal follicular development， thereby exerting an ameliorative effect on PCOS rats.

OBJECTIVE To develop and validate a physiologically based toxicokinetics and toxico?dynamics(PBTK/TD)model for chlorpyrifos(CPF)in rats following both oral and subcutaneous expo?sures to CPF. METHODS ①A PBTK/TD model was established with toxicokinetics and toxicodynam?ics data in literature,which was used for predicting contents of CPF and 3,5,6-trichloro-2-pyridinol (TCP)in blood and activities of acetylcholine esterase(AChE)in the plasma and brain of rats exposed to CPF.②Rats were given 50 mg · kg-1 CPF oral and 50 mg · kg-1 CPF sc simultaneously. Blood and brain samples were collected at 0,1,2,4,6,8,12,24 and 48 h,respectively,after CPF administration (n=5). CPF And TCP contents in plasma,activities of AChE in the plasma and brain were deter?mined,and compared with the simulation values by PBTK/TD model in order to validate the accuracy of the model. RESULTS It was predicted by the PBTK/TD model that after the administration (oral+sc) of CPF 20+20,10+30 and (30+10)mg · kg-1,the concentrations of CPF and TCP in plasma increased and then decreased with time in each group. The inhibitory level of AChE activity in the plasma was orally dose-dependent,while AChE activity of the brain was more sensitive to CPF subcutaneous exposure. The simulation values obtained by the PBTK/TD model were not significantly different from the experimental values obtained by co-administered CPF at(50+50)mg · kg-1. CONCLUSION This CPF PBTK/TD model can quantitatively estimate target tissue dosimetry and AChE inhibition.

OBJECTIVE Calculate the dietary exposure and exposure risk of Chinese consumers to acephate,using the margin of exposure method.METHODS Determine the bench mark dose of acephate by 21 -day gavage experiment of rats.According to the data from the 2002 National Diet and Nutrition Survey,the 2000 -2006 national food conta mination monitoring program,the 2005 -2006 export monitoring data of customs,calculate the dietary exposure of Chinese consumers to acephate by probabilistic assessment.Estimate the exposure risk by co mparing the margin of exposure with 100. RESULTS The bench mark dose of acephate was 0.75 mg·kg -1 ,the BMDL was 0.51 mg·kg -1 .The exposure of children was higher than that of adults.The proportion at risk of group 1 -6 y,7 -17 y and 18 y or higher was 5%,1 % and 0.1 %,respectively.CONCLUSION So me consumers was of dietary exposure risk to acephate.The high exposure of children should be of great concern.