Due to the completion of human genome project and the advent of new technologies, the traditional drug discovery is shifting to genomics-based drug discovery. Target discovery is an important first step in drug discovery pipeline. In this review, we critically introduce the strategies and biology technologies for target discovery, especially focus on the likely impact of new technologies in drug target research and speculate the future trend of target research.

Objective:To investigate the anti-tumor effect of C215gene transfected tumor vaccin e and monoclonal antibody-superantigen fusion protein C215Fab-SEA.Methods:B16 melonoma cells were transfected with the gene encoding a human colon adenoca rcinoma cell-surface glycoprotein C215 to produce a tumor vaccine,melanom a models were established in C57BL/6 mice to observe the antitumor effect of the tumor vaccine and the fusion protein C215Fab-SEA.Results:Tumor growth in mice treated with the vaccine tog e ther with the fusion protein C215Fab-SEA was significantly inhibited comp ared with the control group(P＜0.01),while the tumor growth in group treate d wi th the vaccine only and group treated with the fusion protein only were not obvi ously inhibited compared with the controls.Conclusion:The fusion protein C215Fab-SEA could enh ance the effect of C215-transfected tumor vaccine against the growth of C 215-negative tumors.

Objective:To investigate the anti tumor effect of C 215 gene transfected tumor vaccine and monoclonal antibody superantigen fusion protein C 215 Fab SEA.Methods:B16 melonoma cells were transfected with the gene encoding a human colon adenocarcinoma cell surface glycoprotein C 215 to produce a tumor vaccine,melanoma models were established in C57BL/6 mice to observe the antitumor effect of the tumor vaccine and the fusion protein C 215 Fab SEA.Results:Tumor growth in mice treated with the vaccine together with the fusion protein C 215 Fab SEA was significantly inhibited compared with the control group(P

Aim To observe changes of gene expression profile in rat heart , liver and brain treated with iptakalim using cDNA microarray and analyze its molecule mechanism about pharmacology and treatment. Methods ①Rats were treated with iptakalim for 14 days at a dose of 3 mg?kg-1 by gavage. Total RNA was extracted from heart, liver and brain tissues and reversely transcribed to cDNA, which were labeled with Cy3 and Cy5 fluorescent as probes and hybridized to Gene Chip (BiostarR-40s). Scan array 3 000 was used for scanning the hybridizing signals and ImageGENE 3.0 for data analysis. Data were confirmed using RT-PCR. ②Rats were randomly divided into normal control group and 4 iptakalim groups. Iptakalim was administered orally at doses of 1, 3, 9 mg?kg-1 body weight per day for 2 weeks. The last group was orally administered at a dose of 9 mg?kg-1 body weight per day for 2 weeks, and iptakalim was withdrawn for 10 days. We observe effects of iptakalim on hemodynamics parameters in anesthetized rats and changes of myocardial structure, myofilament ultra-structure after 24h at the end of the last administration. Results ① The new chemical entity iptakalim had selectivity on changes of gene expression in rat heart, liver and brain. Compared with control group, 236 genes are changed (100 increased and 136 decreased) in rat hearts and 6 transcripts (6 increased) in rat livers, there are no changes on gene expression in rat brains. ② In anesthetized rats, iptakalim at doses of 1, 3, 9 mg?kg-1 neither affected pharmacological effects on cardiovascular hemodynamics parameters nor had pathological changes on myocardial morphological and ultrastructure. Conclusion Under the same experimental conditions, the new chemical entity iptakalim has selectivity on changes of gene expression in vital organs. Iptakalim shows no side-effects on cardiac function and tissue structure.

Humans ; Neck Dissection ; methods

[Objective]To research the effect of using Ilizarov technique in bone transmission and fascia skin flap for large defeciency of bone and soft tissues of lower limb.[Method]There were 12 patients in our group,11 patients had severe compound trauma of the leg,one in arm.Bone defeciency range was 4～12 cm,average 8 cm,cotaneous defeciency was 4?5 cm2～14?5 cm2,and all of them had acute infection.Nine had been treated with leg lateral fascia skin flap,1 had been treated with leg fascia skin flap,1 had been treated with the opposide leg skin flap,1 had been treated with the arm fascia skin flap,in 12 bone transport,elongation range was 4～12 cm,average 8 cm.Eight had been used double arms external fixation device,4 cases had been used circle shape external fixation device.[Result]Totally 12 patients were followed up for 2～10.8 years(average,4.2 years) elongation part and compressed part healed naturally,all of the fascia shin flap were alive.No bone ununion and chronic osteomyelitis appeared.[Conclusion]Using Ilizarov bone transport technique and fascia skin flap is a good way for treating large defeciency of bone and soft tissue.Its advantages:(1)The wound limb can maintain stability by external fixatian device.The methed of the bone transportation can fill big section bone deficiency;(2) In the same time the fascia shin flap may be transported,and repair soft tissue deficiency,provide good condition to bone's healing and control infection;(3)The external fixation device can provide distraction and compression functions,this function makes elongation part and compressed part obtain the reasonable biomechanics condition which would be good to bone healing;(4)The course of bone transmission can stimulate bone repair mechanisms,to enhance the wound limb metabolism,increase blood supply circularation,the grown bone factor aggregation,enhance the body's initiative repair mechanisms and infection controlling mechanism;(5)In the protection of the external fixation device,the patient's wound limb can do early rehabilitation,thus can avoid osteoporosis and joint dyfunction because of the lone-term immobility;(6)To use these methods,the treatment period will be shortened,antibiotic application will be decreased,the treatment cost will be lower than other methods and complications will be decreased as well.

Cranial Fontanelles ; physiology ; Humans ; Infant

Objective To investigate the diagnostic value of multidirectional diffusion weighted image (DWI) and apparent diffusion coefficient(ADC) image in acute brainstem infarction.Methods 24 cases of brainstem infarction included 2 cases in super acute stage,22 cases in acute stage.All cases were performed multidirectional DWI,ADC and T1 WI、T2 WI examination including of 2 cases of midbrain,21 cases of pons and 1 case of medulla.All of them were accompanied with infarction of other location.Results Among 24 cases there were 13 cases that their lesions displayed clearly and established by transverse T2WI,transverse、coronary or sagittal DWI、ADC and the diagnostic accuracy was 54.2%.In other 9 cases(37.5%) could not display the signal and extent of the lesions,but they could be confirmed by transverse、coronary or sagittal DWI 、ADC.Moreover there were 2 cases(8.3%) who were indicated accurately the diagnosis by coronary、sagittal DWI 、ADC.Conclusion Multidirectional DWI and ADC could show the location of lesions in the lower brainstem so the multidirectional DWI and ADC scan could be an excellent method for the diagnosis of the brainstem infarction.

In the field of gene delivery, nonviral vectors are getting more attention due to the advantages which do not belong to viral vectors. But kinds of polypeptides are important to construct ideal nonviral vectors. The paper reviews the development in the research of polypeptides as components of nonviral vectors like as the backbone, the targeting moiety, the endosome membrane destabilizing agents and the nuclear localizing signals.

Aim To study effects of rhomotoxin (Rh) on electrophysiologic parameters in rabbit heart. Methods The rabbit hearts in vivo were injected with Rh 12.5 ?g?kg-1 , 25 ?g?kg-1 or saline iv respectively and the isolated rabbit hearts were perfused by Krebs-Henseleit(K-H) perfusion liquid containing Rh 0.34 ?mol?L-1 or 0.68 ?mol?L-1. The electrophysiologic parameters were observed before and after drug adminitration.Results At 20,40,60 and 80 min after injection of Rh 12.5 ?g?kg-1 iv,the VDT,ERP and RRP had no significant changes; but at 20,40,60 and 80 min after injection of Rh 25 ?g?kg-1 iv a significant prolongation of ERP and (or) RRP was found (P