Diversity-oriented synthesis (DOS) aims to efficiently generate collections of small molecules with diverse appendages, functional groups, stereochemistry and skeletons, thus yielding diverse biological activities capable of modulating a wide variety of biological processes. In this review, we discussed the common strategies employed in DOS with specific examples from recent literature, including reagent-based approach, substrate-based approach, build-couple-pair strategy and privileged substructure-based DOS. The application of some DOS libraries in drug discovery is also presented.

Objective: To explore the prevalence of depression in junior school students and its relationship with potential psychological and environmental factors. Method:Depressive symptoms, self-esteem, life events, social support, family cohesion and conflict were investigated with self-report questionnaire in 300 junior school students, the relationship between depression and other psychological or environmental factors were analyzed through stepwise regression. Results:The prevalence of depression in junior high school students was 11%. Among the 5 investigated psychological and environmental factors, self-esteem and social support were negatively related with depression (standardized regression coefficient were -0.59 and -0.14), while life events positively related with it(standardized regression coefficient was 0.26). Only "academic pressure" and another factors covering the item "do not want to go to school" showed a negative association with the students' self-esteem among the 6 factors included in the life events questionnaire (standardized regression coefficient were -0.149 and -0.13).Conclusion: Depression is common among junior school students. Poor self-esteem, lack of social support and negative life events are currently related with the development of adolescent depression. The pressure and failing experiences coming from academic activities are the most influential life events to the development of adolescents' self-esteem.

Objective:To study behavior problems,family factors an d parental rearing styles in students with poor academic achievement.Meth od:Through stratified cluster sampling,488 primary or middle school studen t s were identified as study group(below 5th percentile in their classes),while th e controls were 599 students whose academic achievement were above 95th percent ile in their classes.All subjects completed EMBU,CBCL(children behavior checkli st).Results:Higher boy/girl ratio was pound in study group(326/162) than in control(291/308,? 2=36.4,p

In recent studies,obesity is a risk factor for a variety of cancers,including breast cancer and colorectal cancer.Obesity can regulate the tumorigenesis and development of cancer by some factors,such as insulin and insulin-like growth factor-1 (IGF-1),leptin,fat cytokines and hormones.Understanding the relationship between obesity and cancer can provide a new perspective for the prevention and treatment of cancer.

Objective To understand the expression of heat shock protein(HSP70)mRNA induced by chlorpyrifos in the hepatic tissue of rats.Methods Wistar rats aged 6 weeks were divided into 4 groups,12 in each including 6 male and 6 female,the rats in the experimental groups were treated with chlorpyrifos by gavage once a day at the doses of 17 mg/kg?bw,8.5 mg/kg?bw and 4.25 mg/kg?bw respectively for 14 consecutive days,one group was the negative control.After the exposure,the hepatic tissue was sampled to examine the expression of HSP70 mRNA by polymerase chain reaction(PCR).Results The expression of HSP70 mRNA in the hepatic tissue in the groups of 17 mg/kg?bw,8.5 mg/kg.bw was significantly up-regulated with a dose-response relationship compared with the negative control group.Conclusion The expression of HSP70 mRNA is a sensitive parameter for early exposure assessment of chlorpyrifos.

OBJECTIVE To study the feasibility and security of parotidectomy for parotid benign tumor by tracing cervical branch to expose facial nerve. METHODS Parotid benign tumor of 87 patients were studied.We exposed facial nerve by tracing main facial nerve branch、buccal branch、marginal mandibular branch and cervical branch in parotidectomy for parotid benign tumor and observed the function of facial nerve after operation.RESULTS The number of patients traced by main facial nerve branch- buccal branch、marginal mandibular branch and cervical branch group were 10、8、28 and 41 respctively,and the percentage of facial nerve injury after operation were 30%、37.5%、46.4%and 24.3%.The percentage of facial nerve injury was statistically different between the marginal mandibular branch group and the cervical branch group(P

Farnesoid X receptor (FXR) belongs to the nuclear receptor superfamily. It is highly related to the formation of metabolic syndrome and the glucose homeostasis, and therefore represents an important drug target against metabolic diseases and diabetes. In recent years, great progress has been made in the agonists, antagonists, and crystal structures of FXR. The diverse FXR ligands and their structure-activity relationship are reviewed in this article. The advances in the crystal structures of FXR in complex with different ligands are also introduced.

The objectives of this study are to prepare resveratrol loaded mixed micelles composed of poloxamer 403 and poloxamer 407, and optimize the formulation in order to achieve higher drug solubility and sustained drug release. Firstly, a thin-film hydration method was utilized to prepare the micelles. By using drug-loading, encapsulation yield and particle size of the micelles as criteria, influence of three variables, namely poloxamer 407 mass fraction, amount of water and feeding of resveratrol, on the quality of the micelles was optimized with a central composite design method. Steady fluorescence measurement was carried out to evaluate the critical micelle concentration of the carriers. Micelle stability upon dilution with simulated gastric fluid and simulated intestinal fluid was investigated. The in vitro release of resveratrol from the mixed micelles was monitored by dialysis method. It was observed that the particle size of the optimized micelle formulation was 24 nm, with drug-loading 11.78%, and encapsulation yield 82.51%. The mixed micelles increased the solubility of resveratrol for about 197 times. Moreover, the mixed micelles had a low critical micelle concentration of 0.05 mg · mL(-1) in water and no apparent changes in particle size and drug content were observed upon micelles dilution, indicating improved kinetic stability. Resveratrol was released from the micelles in a controlled manner for over 20 h, and the release process can be well described by Higuchi equation. Therefore, resveratrol-loaded poloxamer 403/407 mixed micelles could improve the solubility of resveratrol significantly and sustained drug release behavior can be achieved.

A novel high performance liquid chromatographic method was developed for the determination of 4-O-methylhonokiol in rabbit plasma and was applied to its pharmacokinetic investigation.Plasma samples were treated by one-fold volume of methanol and acetonitrile to remove the interference proteins.A reverse phase column of SHIMPACK VP-ODS (150 mm× 4.6 mm,5.0 μm) was used to separate 4-O-methylhonokiol in the plasma samples.The detection limit of 4-O-methylhonokiol was 0.2 μg/L and the linear range was 0.012- 1.536 mg/L.The good extraction recoveries were obtained for the spiked samples (84.7％,89.3％ and 87.7％ for low,middle and high concentrations of added standards,respectively).The relative standard deviation of intra-day and inter-day precisions was in the range from 0.6％ to 13.5％.The pharmacokinetic study of 4-O-methylhonokiol was made and the results from the plasmaconcentration curve of 4-O-methylhonokiol showed a two-apartment open model.This work developed a sensitive,stable and rapid HPLC method for the determination of 4-O-methylhonokiol and the developed method has been successfully applied to a pharmacokinetic study of 4-O-methylhonokiol.

A novel high performance liquid chromatographic method was developed for the determination of 4-O- methylhonokiol in rabbit plasma and was applied to its pharmacokinetic investigation. Plasma samples were treated by one-fold volume of methanol and acetonitrile to remove the interference proteins. A reverse phase column of SHIM- PACK VP-ODS （150 mm ×4.6 mm, 5.0 μm） was used to separate 4-O-methylhonokiol in the plasma samples. The detection limit of 4-O-methylhonokiol was 0.2 μg/L and the linear range was 0. 012 - 1. 536 mg/L. The good extraction recoveries were obtained for the spiked samples （84.7%, 89.3% and 87.7% for low, middle and high concentrations of added standards, respectively）. The relative standard deviation of intra-day and inter-day precisions was in the range from 0.6% to 13.5%. The pharmacokinetic study of 4-O-methylhonokiol was made and the results from the plasmaconcentration curve of 4-0-methylhonokiol showed a two-apartment open model. This work developed a sensitive, stable and rapid HPLC method for the determination of 4-O-methylhonokiol and the developed method has been successfully applied to a pharmacokinetic study of 4-O-methylhonokiol.