supported by the National Basic Research Development Program of China(No.2012CB518200);the National Natural Science Foundation of China(No.31071002);the Natural Science Foundation of Hebei Province,China(No.C2012206001);the Science and Technology Program of Hebei Province,China(No.12276104D40,11246125D);the Medical Research Key Projectof Health Bureau of Hebei Province,China(No.20090319)