Identification of the cellular targets of bioactive compounds is a major challenge and a key issue in chemical biology and drug discovery. As an important technology in functional proteomics, small molecule probes play a pivotal role in the identification of cellular targets of bioactive compounds. This review is intended to introduce the application principles and structural design philosophy of chemical probes for the purpose of mechanistic study. Recent cases of successful application were also discussed to further demonstrate the principles and significance ofbioactive small molecule-based probes.

ABSTRACT:Objective To observe the influence of Osthole on cerebral ischemia-reperfusion injury and its acting mechanism.Methods We randomly divided 50 SD rats into sham (Sham)group,ischemia-reperfusion injury (IRI)group and Osthole (25,50,and 100 mg/kg)(Osthole)groups (n=10).The neurological symptoms, extent of cerebral infarction and cerebral water content were evaluated by physical approach.The activities of ROS and ATP were examined by the kit;the mitochondrial membrane potential (MMP ) was measured by flow cytometry.The expressions of Bax,Bcl-2,Caspase3,clevage-Caspase3,Caspase9,clevage-Caspase9,cytoplasmic AIF and cytochrome C were measured by Western blotting.Results Compared with those in sham group,the extent of cerebral infarction and cerebral water content,changes of neurological symptoms,activities of ROS,and expressions of clevage-Caspase3 ,clevage-Caspase9 ,Bax,cytoplasmic AIF and cytochrome C in IRI group were significantly increased (P<0.05).However,the activities of ATP,expressions of Caspase3,Caspase9,Bcl-2 and MMP,and ATP activity were decreased (P<0.05).Compared with those in IRI group,the extent of cerebral infarction and cerebral water content,changes of neurological symptoms,activities of ROS,and expressions of clevage-Caspase3 ,clevage-Caspase9 ,Bax,cytoplasmic AIF and cytochrome C in Osthole group were significantly decreased (P<0.05).But the activities of ATP,expressions of Caspase3,Caspase9,Bcl-2 and MMP,and ATP activities were increased (P < 0.05 ). Conclusion Osthole pretreatment can attenuate cerebral ischemia-reperfusion injury,which is associated with suppressing mitochondria-mediated apoptosis.

Objective The purpose of this study is to confirm the putative association between the Fc?RⅢA-158F/V allele and rheumatoid arthritis (RA) by genotyping the Fc?RⅢA-158F/V polymorphism in patients and controls. Methods One hundred and ninety-two RA patients were recruited and all patients fulfilled the American College of Rheumatology 1987 revised criteria for RA. The demographic data including age, sex and disease duration were collected. The 192 RA patients and 179 control subjects were genotyped for Fc?RⅢA-158F/V polymorphism with a reliable polymorphism assay, nested PCR to investigate whether the Fc?RⅢA-158F/V polymorphism was a risk factor for RA. Results The frequency of Fc?RⅢA-158V/V homozygous was higher in RA patients (OR=3.1, P

100 g).The catheters were removed 1 to 5 days after operation,with transient retention occurring in 5 patients and transient frequency and urgency of urination in 5.At one-month follow-up,the mean IPSS decreased to 11, and mean Qmax increased to 17.8 ml/s. Conclusions The results demonstrate that PVP is safe,efficacious and minimally invasive for patients with obstructive BPH,especially for those of advanced age or at high risk.

Objective To present the preliminary experience on the operative approach in the surgical management of complex posterior urethral stricture. Methods The operative approach of 72 cases of complex posterior urethral stricture was reviewed. Results The total success rate was 89%(64/72). 34 cases were operated with simlpe transperineal approach and the success was rate 91%, transperineal inferior pubic approach was adopted in 14 and the success rate was 93%;simple transpubic approach was conducted in 6 with a success rate of 67% and transpubic perineal approach in 18 with a success rate of 89%. 41 cases with long posterior urethral stricture were operated with a success rate of 85% and 18 cases with complication with a success rate of 94%. Conclusions Each operative approach has it own advantages and disadvantages.Transperineal approach is preferred because the procedure is simpler,less traumatic with less occurrence of complication.

Objective To investigate the effect of liver transplantation on hepatitis B associated diseases and the efficiency of prevention and treatment on the re-infection of hepatitis B.Methods The data of 17 patients undergoing liver transplantation were analyzed after treatment of lamivudine and hepatitis B immune globulin (HBIg). Results Of the 17 cases of hepatitis B pretransplantation, 2 cases were positive for HBsAg. Liver function was normal in all patients.Conclusions Liver transplantation is an effective therapy for hepatitis B. Lamivudine and HBIg could effectively prevent and treat the re-infection of hepatitis B after liver transplantation.

Purpose: To investigate the plasma levels of chemokine IL-8, GM-CSF, RANTES and MCP-1 in patients with breast carcinoma and in healthy controls and to explore its clinical, pathologic and diagnostic significance. Methods: Enzyme linked immunosorbent assay ( ELISA) kits were used in 93 breast cancer patients and 20 health controls, and clinical significance was analysed. Results: The plasma levels of IL-8, RANTES and MCP-1 were significantly higher in the patients than in

Objective Establish a method for qualitative and quantitative analysis of paraquat dichloride in organs in rat by UPLC-MS/MS and study the rat animal model poisoned by intragastric administration of paraquat dichloride to investigate the postmortem distribution of paraquat dichloride in poisoning death rat. Methods The rats were given an intragastric administration of 1/2LD50 Paraquat dichloride. The rats were dissected at 0.5h, 2h, 4h, 8h, 12h, 24h, 48h, 72h respectively after the intragastric administration. The specimens of -the heart, liver, spleen, lung, kidney, brain, muscle, bladder and stomach-were collected and analyzed immediately. Qualitative and quantitative analysis were performed by UPLC-MS/MS. Results Within 4h, stomach is the main distribution organ. The content of paraquat dichloride is the highest in stomache and relatively low in other organs. The concentration of organization except stomach changed little within 4h. The concentration of stomach has a sharp decline after 4h. The concentration in organs except stomach has a sharp rise after 4h. There is a significant difference(P<0.05) between each organs and brain. Conclusion There was a postmortem maldistribution of paraquat dichloride in poisoning death rats and the concentration in organs changes with time. The analysis method of UPLC-MS/MS and postmortem distribution of paraquat dichloride can be applied to the forensic identification of paraquat dichloride poisoning death and provide direction for delete this part toxicology analysis.

By tracing of ~(75)Se-Na_2SeO_3 incubating and irrigating of the isolated myocardial slices of rats, the numeric relationship between the free selenics in the serum and the serum sdenics, the sodium sdenite doses injected were observed; the absorption of the frce selenics and the serum selenics was compared; the setenics metabolic rate and quantities of the myocardial tissue in different duration after injecting of selcnite, the effect of selenics concentration to the participating were calculated, It is suggested that there is a very close relationship between the free selenics and the selenium metabolism in the myocardium; the ratio betwen the values of the free selenics and the serum selenics may become a stable indicator of the selenium metabolism; the free selenics in the serum may be where the important mediates of selenium metabolism are.

Objective To investigate the relationship between dose and trough blood concentration of tacrolimus after orthotopic liver transplantation and the changes of time-dependent concentration. Methods The doses and trough blood concentrations of tacrolimus from 20 patients who survived longer than 1 year were summarized retrospectively.Results The initial oral doses of 0.15 mg?kg -1?d -1 as suggested by most surgeons led to 53.4 % of the measured whole blood concentrations in the first postoperative week were higher than 15 ?g/L, 23.3 % of them within 10 ?g/L to 15 ?g/L and 23.3 % of them lower than 10 ?g/L. The ratio of trough concentration/dose was increased gradually after transplantation and reached its peak at the second postoperative month, which was higher than those in the following month 3, 4, 5, 6, 7, 8 and 11 significantly (all P