Poly(ADP-ribose)polymerase-1 (PARP-1) plays a significant role in the DNA repair process by catalyzing the transfer of ADP-ribose from NAD+ to its receptors. It is a promising anticancer drug target and many PARP-1 inhibitors have been developed and used in the clinical trial. In this work, a series of 3-(2-oxo-2-substituted acetamido)benzamides have been synthesized and their inhibitory activities against PARP-1 were evaluated. Of all the tested compounds, six compounds displayed inhibitory activities with IC50 values ranging from 0.23 to 5.78 µmol.L-1 . The binding pose of compound 5a was predicted using molecular docking to facilitate further structural modification.
Antineoplastic Agents ; Benzamides ; chemistry ; DNA Repair ; Drug Design ; Humans ; Molecular Docking Simulation ; Poly(ADP-ribose) Polymerase Inhibitors ; chemical synthesis ; chemistry ; Poly(ADP-ribose) Polymerases

Animals ; Chemokine CCL11 ; metabolism ; Guinea Pigs ; Respiratory Mucosa ; metabolism ; Rhinitis, Allergic, Seasonal ; metabolism

Objective To observe the effect of continuous incision infusion different concentra-tion of ropivacaine for postoperative analgesia after radical mastectomy.Methods One hundred pa-tients under radical mastectomy,aged 40-70 years,ASA Ⅰ or Ⅱ,were randomly divided into four groups (n =25 each):0.2% (group R1),0.3% (group R2),0.4% (group R3)ropivacaine incision continued infiltration group and patient-controlled intravenous analgesia (group PCIA)as control group.VAS pain scores,sedation Ramsay score and side effects were recorded at each time point in rest and turning over 90°,2 h (T1 ),4 h (T2 ),8 h (T3 ),12 h (T4 ),24 h (T5 ),48 h (T6 )after the operation.Results VAS scores in group R1 at T1-T6 in rest and turn over 90°were significantly high-er than that of group PCIA (P <0.05).There were no significant differences among the group PCIA, group R2 and group R3.Sedation score in PCIA group was significantly higher than that in the other three groups (P <0.05),and the adverse reactions,such as nausea and vomiting,in group PCIA (2 cases)were more serious than that in the other groups (0 cases ).There were no significant differences among the other groups.Conclusion Ropivacaine plays an effective role in infiltration an-algesia when its concentration reaches 0.3% subcutaneous after radical mastectomy.

Objective To detect the esophageal and fundal varices and their related collateral ves-sels by multi-detector row CT ( MDCT) in helping to find out the objective evidences for selecting treatment measure and predicting prognosis. Methods Fifty-one patients with clinical diagnosis of cirrhosis were in-cluded in this study. Esophageal varices were confirmed by endoscopy in all patients, of which 31 accompa-nied with fundal varices. All patients underwent MDCT angiography to demonstrate collaterals between the systemic and portal circulation as well as the esophageal varicose. Results Good or excellent image quality was obtained in all patients. Gastric fundal varices were found in 31 of 51 patients (60. 8% )by endoscopies. By MDCT angiography esophageal varies were confirmed in all patients, gastric fundal varices were in 32 of 51 (62. 7% ). There are high degree of concordance Kappa =0. 876 between them. Esophageal varices were supplied mainly by the left gastric vein ( LGV) , by anterior branch of LGV alone in 30 of 51 (58. 8% ). There were paraesophageal veins in 21 of 51 patients (41.2%). Gastric fundal varices were supplied by LGV in 24 of 32 patients (75% ), by short gastric veins /posterior gastric veins in 3 of 32 patients (9. 4% ) and by short gastric veins /posterior gastric veins and LGV together in 5 of 32 patients ( 15. 6% ). Short gas-tric veins and posterior gastric veins participate in forming of esophageal varices in these patients. Conclusion MDCT angiography shows an excellent vascular maps and highly in concordance with endoscopy in terms of the detection of esophageal and gastric fundal varices. Esophagal varices were supplied mainly by LGV, more than half of them were by its anterior branch, and paraesophageal veins participated to it in some patients too. The blood flow in gastric fundal varices were supplied from LGV in most of the patients, and the rest from short gastric veins.

Objective To evaluate the effectiveness of arthroscope-assisted surgical technique in treating knee fractures and knee peripheral fractures.Methods From September 2000 to December 2005,there were 46 cases with knee or knee peripheral fractures,in whom artbroseope-assisted surgical technique was performed in 36 cases including 24 males and 12 females,with mean age of 30.5 years (18-52 years).Of 36 cases,26 cases with patella fractures were treated by internal fixation of tension band using cancellous bone screws,four with distal end femoral fractures by retrograde interlocking using intramedullary nail and six with fractures of tibial plateau and tibial condyle crista by internal fixation u- sing cancellous bone screws.Results The mean hospitalization was eight days.A follow up for 3-36 months(average 14 months)in 36 cases showed fracture healing.Of 36 cases,32 cases regained full knee range of motion,four left with terminal flexion,with mean loss of 15?,and had thigh circumference (10 cm above knee)1.1 cm(range 0.6-2.0 cm)shorter than health side and two had slight pain in the knee joint.Lysholm knee joint function score was 86.5+7.6 for patellar fractures,tibial plateau frac- tures and condylar crista fractures.Conclusion As for knee or knee peripheral fractures,arthroscope- assisted surgical technique can provide fine monitoring,decrease trauma and complications,fixate inter- nally and help early ground exercise.

Poly ?-glutamate is a biopolymer material that has a good application prospect.The Vitreoscilla hemoglobin(VHb) gene was integrated into the chromosome of Bacillus licheniformis WX-02 by integrative vector pDG1730-vgb.The expression of VHb was confirmed by CO-difference spectra analysis.It was shown by the results of batch cultures in a 3 L bioreactor that biomass and ?-PGA obtained in the recombinant M2 were 25.5 % and 20% higher than those of the control respectively.

Signal transducer and activator of transcription 3 (STAT3) is an important regulatory factor of cell proliferation and metastasis, involved in the occurrence and development of a variety of malignant tumors, and it is one of the hot spots in the research of targeted anti-tumor drugs. Our group screened a novel benzobis (imidazole) structure small molecule compound LZJ541 through the screening model of Janus kinase (JAK)/STAT3 pathway inhibitors, which has definite STAT3 inhibitory activity. We examined the effect of LZJ541 on the proliferation of HepG2 and PC-3 cells by MTT assay in vitro, detected the effect of LZJ541 on the expression of STAT3-related proteins in HepG2 cells by Western blot, and measured the effect of LZJ541 on the apoptosis and cell cycle arrest of HepG2 cells via flow cytometry. The results indicated that LZJ541 significantly inhibited the activation of STAT3 signaling pathway and restrained the proliferation of HepG2 cells. Its half maximal inhibitory concentration (IC₅₀) was 13.8 μmol·L^-1, which was much lower than that of PC-3 cells (with low STAT3 expression, IC₅₀: 41.99 μmol·L^-1), LZJ541 can also inhibit the phosphorylation of STAT3 in HepG2 cells, thereby inducing apoptosis and cycle arrest and then exerting anti-tumor effects. In conclusion, LZJ541 has a certain anti-tumor effect in vitro, which provides an experimental basis for the development of new STAT3-targeted anti-tumor drugs around this kind of compounds.

Animals ; Disease Progression ; Kidney Diseases ; physiopathology ; Kidney Glomerulus ; drug effects ; pathology ; Rats ; Renal Agents ; pharmacology ; Renin-Angiotensin System ; drug effects ; Sclerosis

ObjectiveTo investigate the value of a digital three-dimensional reconstruction technique in the treatment of hepatic alveolar echinococcosis (HAE).MethodsThe computed tomography scan data for 13 patients with HAE who were admitted to the First Affiliated Hospital of Xinjiang Medical University from February 2011 to October 2011 were reconstructed and analyzed by a three-dimensional reconstruction system to assess resectability,and to facilitate surgical planning and individualized virtual surgery.The results of preoperative analysis were compared with the results of actual operations.ResultsThe three-dimensional models of the liver were reconstructed successfully,and intrahepatie lesions and vessels were clearly displayed.One patient received an autologous liver transplantation,10 underwent hepatectomy,and 2 received percutaneous transhepatic cholangial drainage.Virtual operation planning was carried out for 11 patients using the three-dimensional reconstruction system.The mean volume of the liver to be resected was predicted to be 920 ml (range,339-2678 ml),and the mean percentage of liver to be resected to the total liver volume was predicted to be 45％ ( range,23％ -68％ ).The mean volume o[ the actual liver resection was 834 ml (range,315-2250 m[),and the mean percentage of actual liver resected to the total liver volume was 42％ (range,22％ -70％ ),which was consistent with the results of preoperative three-dimensional reconstruction.All patients were followed up for 2-8 months,and no severe complications such as liver failure,hemorrhage and bile leakage were detected.ConclusionDigital three-dimen-sional reconstruction is helpful in the diagnosis and treatment of HAE and effectively reduces surgical risks.

Objective To investigate the prevalence of and predisposing factors of atopic dermatitis (AD ) in 0 - 6 year-old children in rural and urban area of Tianjin. Methods The subjects were chosen by cluster sampling from kindergartens in Tianjin's urban and rural districts. Questionnaires were designed based on the International Study of Asthma and Allergies in Children (ISAAC ) and distributed to the children's parents via the teachers. Results In this survey, 3 749 questionaires were returned, of which 3 708 were valid. The response rate was 82.7% in total, 79.3% in the rural area, and 84.9% in the urban area. The age and gender distributions were similar in the urban and rural area. The prevalence rate of AD in these children was 2.9% in total, and it was higher in the urban area than in the rural area (3.5% vs 2.4%, x2 = 3.98, P