Child, Preschool ; Fibroma ; pathology ; Humans ; Male ; Oropharyngeal Neoplasms ; pathology

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.
Drug Design ; Drug Discovery ; Small Molecule Libraries

Antineoplastic Agents ; adverse effects ; Drug-Related Side Effects and Adverse Reactions ; therapy ; Humans ; Neurotoxicity Syndromes ; therapy

Background Diabetes mellitus (DM) can provoke the apoptosis of retinal cells and downregulate the expression of calcitonin gene related peptide (CGRP) in the retina.Capsaicin promotes the release of CGRP and elicits protective effects on human organs.However,whether CGRP protects retinal cells in diabetic retinopathy (DR) is still unclear.Objective The study was designed to examine the effect of capsaicin on the apoptosis of retinal cells in diabetic rats and its relationship with CGRP.Methods Forty clean healthy adult male Sprague-Dawey rats were randomly divided into the diabetes group,capsaicin pretreated group,streptozocin (STZ)control group,capsaicin control group and plain control group,with 8 rats per group.The diabetic model was established by the intraperitoneal injection of 60 mg/kg in all rats except those of the plain control group.0.4 mL of a 1％ capsaicin injected at 20 mg/kg was subcutaneously injected for 3 consecutive days prior to model establishment in the capsaicin pretreated group,after which 1.2 mL of STZ was intraperitoneally injected on the fourth day.Rats from the STZ control group were administered intraperitoneally 1.2 mL of 0.1 mol/L,pH 4.5,citrate buffer.The capsaicin control group received subcutaneous injections of 0.4 mL of 1％ capsaicin at 20 mg/kg for 3 consecutive days,after which 1.2 mL of 0.1 mol/L,pH 4.5,citrate buffer was administered intraperitoneally.The rats were sacrificed at the tenth week after model establishment and retinal specimens were prepared for the apoptosis assay by TUNEL staining and the quantitative analysis of caspase-3 activity.Expression of CGRP in the retina and serum was detected using ELISA.The use of experimental animals followed the Regulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.Results Retinal cell apoptosis was mainly localized to the retinal ganglion cell (RGC) layer.The apoptosis rate of RGCs was (43.4±5.0)％ in the DR model group and (30.0±5.1)％ in the capsaicin pretreated group,showing a significant difference (t =5.930,P＜0.01).Compared with the DR model group and capsaicin pretreated group,the apoptosis rates of the DR control group (12.4±9.9) ％ and the capsaicin control group (17.6-±6.1) ％ were significantly lower (t =8.800,t =4.925,P＜0.01).The apoptosis rate of the plain control group was (16.2±6.9)％,exhibiting significant differences in comparison with the DR control group and capsaicin control group (t =-0.989,t =0.951,P＞0.05).The specific activity of caspase-3 was (2.19±0.86) in the DR model group and (1.96±0.56) in the capsaicin pretreated group,presenting a significant difference (t =-0.515,P＜0.05).Those of the DR control group and capsaicin control group were (1.47±0.14) and (0.74±0.27),respectively,with considerable decline in comparison with the DR model group and capsaicin pretreated group (t=2.142,t=2.797,P＜0.05).The retinal and serum CGRP levels were (424.4±44.2)and (148.8±39.1) ng/L,respectively,displaying significantly lower levels than (543.2±74.4) and (237.5±78.7) ng/L (t =3.070,2.359,P＜0.05) from the capsaicin pretreated group.Conclusions Apoptosis of retinal ganglion cells occurs in the STZ-induced diabetic rats.Pretreatment of capsaicin reduces retinal cell apoptosis,which may be associated with an increase of CGRP in the retina.

Age-related macular degeneration (AMD) and cataract are the most common causes of low vision worldwide.Nowadays, there is still a controversy about whether cataract surgery should be taken in patients combined with AMD and when should the surgery be taken.The aim of this review is to assess the influence of cataract surgery on the occurrence and development of AMD, to analyze the risk factors, to explore the occasion of cataract surgery in patients with AMD, and joint with anti-vascular endothelial growth factor (VEGF) treatment, also including the development and application of intraocular lens.It helps to avoid and postpone the development and progression of macular degeneration after cataract surgery and get good visual outcome.

Objective To discuss the protective effects of thioltransferase (TTase) on oxidative damaged human lens epithelial cells (HLEC) induced by ultraviolet radiation.Methods HLEC were cultured in vitro and then randomly divided into 4 groups:Normal group:normal cultured HLEC;UV group:normal cultured HLEC + UV radiation (with 302 nm UV radiation irradiation intensity 55.56 μW · cm-2 for 15 minutes,totaling irradiation volume 500 J · m-2);TTase siRNA group:HLEC transfected with TTase siRNA;TTase siRNA + UV group:HLEC transfected with TTase siRNA + UV radiation(with 302 nm UV radiation irradiation intensity 55.56 μW · cm-2 for 15 minutes,totaling irradiation volume 500 J · m-2).TTase mRNA expression was measured by qRT-PCR,the cell proliferation was detected by LDH Assay Kit,and the TTase activity was measured.TTase expression was detected by Western blotting.The levels of TGSH,GSH and GSSG of HLEC were measured,and then GSSG/T-GSH ratio was calculated.Results Cell proliferation ability in UV group,TTase siRNA group and TTase siRNA + UV group were decreased by 21.0％,17.0％ and 29.0％ compared with normal group (all P ＜ 0.05).TTase activity in UV group was 2.1 times of the normal group,TTlase siRNA group was 67.0％ of the normal group,Tlase siRNA + UV group was 1.3 times of TTase siRNA group (all P ＜ 0.05).TTase expression in UV group was 3.9 times of the normal group,TTase siRNA group was 35.0％ of the normal group,TTase siRNA + UV group was 3.0 times of siRNA group (all P ＜ 0.05).GSH content in UV group,TTase siRNA group and TTase siRNA + UV group were 68.4％,79.0％,61.7％ of the normal group (all P ＜ 0.05).GSSG content in UV group,TTase siRNA group and TTase siRNA + UV group were 2.3 times,1.4 times,3.7 times of the normal group (all P ＜ 0.05).GSSG/T-GSH in UV group,TTase siRNA group and TTase siRNA + UV group were 3.1 times,1.7 times,5.2 times of the normal group (all P ＜ 0.05).Conclusion TTase plays an important protective role in oxidative damaged HLEC induced by ultraviolet radiation.

Since the first paper reported the finding of genetic variation contributing to human age-related macular de?generation by genome-wide association study (GWAS) in 2005, large number of human complex diseases associated genetic variants have been identified through GWAS method. However, the biological function of these genetic variants is not very clear. The present paper reviewed the methods of fine-mapping and the progress of the functional studies for these suscepti?bility variants. In the post GWAS Era, the study of genetic mechanisms can help us to understand the disease pathogenesis.

0.05). Conclusion Brachytherapy ,when used to increase the dose effect,may enhance the local effect without any change in the overall survival.

Objective To investigate the clinical efficacy of methotrexate and mifepristone in treatment of ectopic pregnancy. Methods 58 cases with ectopic pregnancy admitted in the Second People's Hospital in Putuo district of Zhoushan city from February 2010 to February 2012 were randomly divided into observation group and control group,each had 29 cases. Control group were received methotrexate 1 mg/kg or 50 mg/m2 once a day by intramuscular injection,observation group were given both methotrexate and mifepristone treatment,the mifepristone was given one piece a day and each piece is 75 mg. the treatment success,b-HCG returned to normal time,normal pregnancy and the occurrence of complications were compared between two groups. Results The treatment success and normal pregnancy rate in observation group were significantly higher than control group(P<0.05),b-HCG returned to normal time was significantly shorter than control group (P<0.05 ). There were no obvious adverse reactions in both two groups, observation group had one light nausea,and control group had one light nausea and one case with alanine aminotransferase (ALT)slightly increased phenomenon,those patients were all back to normal on their own without treatment,the difference of adverse reaction rate between two groups was not significant. Conclusions Methotrexate and mifepristone has good efficacy and are safe and reliable in,treatment of ectopic pregnancy.