Dental Porcelain ; Dental Prosthesis ; Dental Restoration, Permanent ; methods ; Humans

Idiosyncratic adverse drug reactions (IDR) induce severe medical complications or even death in patients. Alert structure in drugs can be metabolized as reactive metabolite (RM) in the bodies, which is one of the major factors to induce IDR. Structure modification and avoidance of alert structure in the drug candidates is an efficient method for reducing toxicity risks in drug design. This review briefly summarized the recent development of the methodologies for structure optimization strategy to reduce the toxicity risks of drug candidates. These methods include blocking metabolic site, altering metabolic pathway, reducing activity, bioisosterism, and prodrug.
Binding Sites ; Cytochrome P-450 Enzyme System ; metabolism ; Drug Design ; Drug Discovery ; methods ; Drug Recalls ; Drug-Related Side Effects and Adverse Reactions ; prevention & control ; Humans ; Structure-Activity Relationship

Humans ; Laryngeal Neoplasms ; Male ; Middle Aged ; Sarcoma

Child ; Female ; Hamartoma ; diagnosis ; pathology ; surgery ; Humans ; Tracheal Diseases ; diagnosis ; pathology ; surgery

AIM To explore the protective effects and mechanisms of dihydromyricetin (DHM) against non-alcoholic fatty liver disease (NAFLD) in ApoE-/-mice.METHODS The 40 male healthy six week-old ApoE-/mice were randomly divided into model group,DHM (50,100 mg/kg) group and Bicyclol group.Ten male C57 mice were used as the control group.The control and model groups were administrated with 0.5％ CMC-Na solution and the other three groups were given DHM [50,100 mg/(kg-d),i.g.] and Bicyclol [140 mg/(kg · d),i.g.].All mice were fed with high fat diet (0.3％ cholesterol,20％ fat) for 12 weeks.At the end of the experiment,the blood was collected from the orbit and the serum was separated for blood lipid detection.AST and ALT expression levels were detected by automatic biochemical analyzer.HE staining and oil red O monitored the liver injury and lipid accumulation.The oxidase enzymes were measured by the commercial kits.The hepatocyte apoptosis was determined by TUNEL assay,and the Bcl-2,Caspase-3 expression levels were detected by immunohistochemistry.The AMPK and phosphorylation of AMPK expression levels were determined by Western blot.RESULTS After the treatment,liver lipid accumulation and liver injury,TUNEL postive cells sharply increased compared with the control group.Meanwhile,the Caspase-3 expression level was significantly upregulated and the Bcl-2 was markedly downregulated in the model group.DHM [50,100 mg/(kg · d)] remarkably reduced AST and ALT levels,liver lipid accumulation and TUNEL positive cells and modulated oxidase enzymes expression level compared with the model group.Moreover,DHM obviously increased Bcl-2 expression and decreased Caspase-3 expression in liver tissue,and inhibited AMPK phosphorylation.CONCLUSION DHM reduces the lipid accumulation and protects liver injury from high fat diet induced NAFLD mice,the protective mechanism of DHM may be related to inhibiting AMPK phosphorylation and inhibiting hepatocyte apoptosis.

Objective The aim of this paper is to know about the pollution of microcystin-LR(MC-LR)in Fenhe First reservoir and Fenhe Second reservoir in Taiyuan and provide reference for making the policy of prevention microcystin-LR pollution.Methods During the low water period(May,2005)and common period(Oct,2005),5 liter water was sampled in the entrance,the center and the exit in Fenhe First reservoir and Fenhe Second reservoir respectively.The concentrations of MC-LR in two reservoirs were determined by the high-performance liquid chromatography(HPLC).Results The average concentration (0.875 ?g/L)of MC-LR in low water period was 3 time of that(0.283 ?g/L)in common period in Fenhe First reservoir.The average concentration(0.815 ?g/L)of MC-LR in low water period was 17 time of that(0.048 ?g/L)in common period in Fenhe Second reservoir.The level of MC-LR in the entrance was the highest,that in the exit was the lowest,that in the center was middle. The concentration of MC-LR of the entrance in low water period was more than the MC-LR limit(1 ?g/L)in Life drinking water hygienic guide(2001).Conclusion MC-LR pollution has been found in Fenhe First reservoir and Fenhe Second reservoir and the pollution is serious in low water period.

Factor Analysis, Statistical ; Health Policy ; Leadership ; Occupational Health Services ; organization & administration

Cerebral Infarction ; drug therapy ; etiology ; Female ; Humans ; Infant, Newborn ; Intracranial Hemorrhages ; drug therapy ; etiology ; Male ; Vitamin K Deficiency ; complications ; drug therapy

Objective To estimate blood lead level of children in Jinchang city of Gansu province.Methods According to relevant request,256 children(male 133,female 123) aged 2-7 years from some kindergartens in Jinchang city were randornly selected from Oct. 2004 to Jun. 2005. Blood lead level was measured by atom-absorbing graphiteingle method.Results The average blood lead level of 256 children was(126.30?52.98)?g/L.The lowest blood lead level was 28.3 ?g/L while the highest was 268.0 ?g/L.And 160 children(62.54%) were found with a blood lead level ≥100 ?g/L(the diagnostic level of lead poisoning in children).The blood lead level became higher with the increase of children′s age,as groups aged 2-3 years group were lower than aged 5-6 years and 6-7 years groups,of which the differenes had statistical significance(P0.05).Conclusion Blood lead levels of children in Jinchang city and prevalence of lead poisoning are both relatively higher,to which enough attention shall be paid.

Objective To analyze the clinical and radiographic features of short stature combined with skeletal deformity in children,and to diagnose exactly and cure promptly in children.Methods One hundred and twenty children were collected,included 69 males and 51 females.All of the children were collected detail medical history including history of birth,feeding,growth and development and family history and taken both physical and X ray examination that bone age could be evaluate by Gruelich-Pyle method.The children were taken a laboratory examination including calcium,phosphours,alkaline phosphatase,chromosome karyotype,and so on.Results Among 120 children,there were 36 cases(30.0%) of achondroplasia,20 cases(17.0%)of Turner syndrome,10 cases(8.0%)of multiple epiphyseal dysplasia,1 case(0.8%)of spondyloepiphseal dysplasia congenital,7 cases(5.8%) of spondyloepiphyseal dysplasia tarda,2 cases(1.6%) of osteogenesis imperfecta,1 case(0.8%) of cleidocranial dysplasia,5 cases(4.2%)of mucopolysaccharide Ⅳ,5 cases(4.2%) of pseudoachondroplasia,9 cases(7.5%)of hypophosphatemic ricket,24 cases(20%)of short limb dwarf.Among 120 cases,27 were regularity dwarfism(22.5%),93 cases were irregularity dwarfism(77.5%);Among 93 cases of irregularity dwarfism,80 cases were short limb dwarfism including 36 cases of short upper limb(short upper arm 35 cases,shortforearm 1 case),20 cases of short lower limb,24 cases of proportional short stature,13 cases of short trunk.X ray bone age lag 46 cases,ahead of schedule 15 cases(12.5%),normal 59 cases.Conclusions The main causes of short stature combined with skeletal deformity are genetic bone disease.To analyze the feature of clinical and radiographic is a valuble instrument for the children diagnosis of short stature combined with skeletal deformity.Part of them skeletal age were lagged.