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

Objective To explore the efficacy of various managements of indurative biliary fistula after HCE operation.Methods 31 patients who underwent surgery for indurative biliary fistula after HCE operation in Xinjiang Medical University were studied retrospectively.Cholangiography and common bile duct exploration through a T tube were done in 15 patients,cholangiography and decompression through a T tube which led to the orifice of the fistula of the cavity in 8 patients,hepatectomy in 4 patients,lobe resection + choledochojejunostomy in 2 patients,total pericystectomy in 1 patient,and cavity abscess debridement in 1 patient for severe infection of the abdominal cavity,followed by hemihepatectomy after half a year.Result On follow-up of 1-8 years,choledochojejunostomy had to be done in 1 patient for stricture of the bile duct after T tube drainage,hepatectomy in 1 patient for bile leakage after the cavity abscess debridement operation,and bile leakage in 1 patient after hepatectomy although with drainage the patient was cured.Conclusion The results suggested that hepatectomy and total pericystectomy completely solved the problems arising from indurative biliary fistula.However,these procedures are complicated,and have higher operative risks.Cholangiography and common bile duct exploration solved the cavity-related problems.For patients with severe calcified cavities which communicated with large hepatic ducts,cholangiography and decompression through a T tube put into the orifice of the fistula of the cavity solved the indurative biliary fistula efficaciously and safely.

Abstract?AIM: To obtain the prevalence and risk factors of symptomatic dry eye disease ( SDED ) among college students in China.?METHODS:Population-based cross-sectional study. Students in Medical School of Lanzhou University were approached. A questionnaire was used to evaluate the prevalence of SDED and its risk factors. The diagnosis of SDED was based on reported symptoms and was established if the participants reported “often” or “all the time” once or more for 6-item questionnaire. Positive tests included a tear-film breakup time ( TBUT)≤10s and a fluorescein staining score ( FSS ) ≥1. Demographic information and possible factors that may contribute to SDED were analyzed in a step-wise multivariate logistic regression modelto assess risk factors of SDED.? RESULTS: There were 1139 participants ( 84. 37%response rate ) have completed the questionnaire, 475 males and 664 females aged 16-26y. The prevalence of SDED was 18. 70% [95% confidence interval ( CI)= 16. 59-20. 81]. A TBUT of ≤10s and a FSS≥1 were noted in 47. 67%(95% CI=44. 95-50. 57) and 13. 97%(95% CI=11. 95-15. 99) for all participants, respectively. The multivariate regression analysis revealed the following risk factors:daily reading time of≥4h(OR=1. 58,95% CI=1. 15-2. 18), daily computer use of≥4h ( OR= 1. 52, 95% CI= 1. 02-2. 25), and constant eyeglasses wearing (OR=1. 54,95%CI=1. 08-2. 13). The female gender, refractive surgery and contact lens ( CLs) wearing were not risk factors for SDED in this analysis.? CONCLUSION: The prevalence for SDED is high in Chinese college students. The risk factors include daily reading time of≥4h, daily computer use of≥4h and constant eyeglasses wearing.

A two-step method for the purification of blocking-type anti-human CD80 monoclonal antibody 4E5 from mouse ascites was developed using anion exchange and gel filtration in combination. The ascites was first purified by anion exchange after centrifugation and filtration. The experimental parameters of sample loading and elution were optimized. The optimized loading condition was pH 8.0,50 mmol/L Tris-HCl and satisfactory results were obtained using a 0~0.5mol/L NaCl step elution. The fraction containing the protein of interest was directly loaded on gel filtration column and eluted using a 20 mmol/L phosphate buffer at pH 7.2. The purity of the obtained monoclonal antibody was up to 95% with a recovery of 61%. The purity of mAb could efficiently inhibit the growth of Daudi cells. The amplification of the method was also studied using a Bio-Scale Q5 column and the result was satisfied.

In order to clarify the pharmacodynamic substances and mechanism of Xiangju Preparations (Xiangju Tablets, Xiangju Drops) in the treatment of rhinitis and sinusitis, the multi-level network integration analysis of "ingredients-targets-pathways" was conducted. 137 chemical constituents were identified in Xiangju Preparations by high pressure liquid chromatography-quadrupole-time of flight mass spectrometry (HPLC-QTOF/MS) for the first time. Network pharmacology analysis was performed on 59 potential active components. The results of network pharmacology analysis demonstrated that the medicinal ingredients in Xiangju Preparations included caffeic acid, senkyunolide F, rosmarinic acid, ligustilide, prim-O-glucosylcimifugin, linarin, magnolin, luteolin, senkyunolide I and gallic acid. These ingredients act on the crucial targets of tumor necrosis factor (TNF), interleukin 1B (IL1B), protein kinase B (AKT1), vascular endothelial growth factor A (VEGFA), signal transducer and activator of transcription 3 (STAT3) and participate in the regulation of advanced glycosylation end products-receptor of AGEs (AGE-RAGE), TNF, nuclear factor kappa B (NF-κB), and cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling pathways to effectively treat rhinitis and sinusitis. The excellent binding performance between above 10 active components and 5 key target proteins was further confirmed by molecular docking, indicating that these 10 ingredients are pharmacodynamic substances of Xiangju preparations. In conclusion, this study preliminarily clarified the effective components and mechanism of Xiangju preparations in the treatment of rhinitis and sinusitis, and provided a theoretical basis for the clinical application of Xiangju preparations.

Objective To observe changes of hepatic hemodynamics and hepatic functional reserve after splenectomy and periesophagogastric devascularization. Methods From July 2006 to August 2007, thirty patients with portal hypertension caused by hepatitis B cirrhosis underwent splenectomy and periesophagogastric devascuiarization. The PVPG (portal venous pressure gradient) was measured by inductor continually during operation. The HAF (hepatic artery flow), PVF (portal venours flow) and hepatic arterial RI(resistant index) were measured with Doppler sonography. The EHBF(effective hepatic blood flow) and ICGR15 (indocyaninegreen retention rate at 15 minutes) were obtained respectively by indocyaninegreen clearance test before and after the operation. Results PVPG after laparotomy (19±4) mm Hg, ligating the splenic artery(14±4) mm Hg, splenectomy(14±3)mm Hg and periesophagogastric devascularization (12±4) mm Hg showed a tendency to decrease progressively. The PVF decreased [from (42±14) ml/s to (16±8) ml/s] and HAF increased in compensation after operation. The EHBF increased [from (0.48±0.10) L/min to (0.56±0.10) L/min], and the ICGR15 decreased (from 23%±8% to 18%±4%) postoperatively. Conclusion After splenectomy and periesophagogastric devascularization, the hepatic functional reserve improves at least in a short term notwithstanding the decrease of PVPG and PVF.

Objective To prepare a kind of Gelsolin-targeted ultrasound contrast agent (GSN-PLGA) and to explore its targeting and imaging effection in vitro.Methods The high molecular PLGA-COOH ultrasound contrast agents were prepared by a modified double emulsion technique and then conjugated with Gelsolin monoclonal antibody by carbodiimide technique.The physical property of contrast agent was determined.And the connectivity condition of ultrasound contrast agent with Gelsolin monoclonal antibody was estimated.The targeting ability and the effect of enhancing ultrasound imaging in vitro were explored.Results The average diameter of GSN-PLGA was (575.67 ± 4.71) nm.The potential was (-11.46±1.19) mV.And the binding rate of Gelsolin monoclonal antibody was 96.93％.In vitro experimentshowed more GSN-PLGA could be intaked by Hca-F cells and the ultrasound imaging cloud be enhanced greatly.Conclusion The GSN-PLGA nanoparticle can bind to Hca-F cells specifically and can enhance the ultrasound imaging greatly.

To explore the effects of psychological capital social support and their interaction on job satisfaction in Methods natural gas field workers. A total of 1 473 workers from a natural gas field were selected as the research subjects ， using convenient sampling method. Job Satisfaction Questionnaire Psychological Capital Questionnaire and Social Support ， Results Scale were used to investigate the scores of job satisfaction psychological capital and social support level. The ， ， detection rates of job satisfaction psychological capital and social support in the high level group were 55.9% 52.5% and ， 48.1% respectively. The detection rates of job satisfaction of workers in the high level psychological capital group and high level （ social support group were higher than those in the low level psychological capital group and low level social support group 67.4% vs ， vs ， P ） 43.3% 71.9% 41.2% all <0.01 . The results of multivariate logistic regression analysis showed that psychological capital ［ （CI） （ - ） and social support had positive effects on job satisfaction odds ratio and 95% confidence interval were 1.58 1.17 2.41 （ - ）， ， P ］ ， and 2.53 1.82 3.52 respectively all <0.01 . Moreover the psychological capital and social support had additive effect on ［ CI （ - ）， CI job satisfaction relative excess risk of interaction and 95% was 3.07 1.02 5.12 attributable proportion and 95% was （ - ）， CI （ - ）］， 0.48 0.35 0.61 synergy index and 95% was 2.34 1.72 3.16 but there was no multiplication interaction between （P ）Conclusion psychological capital and social support >0.05 . Psychological capital and social support can positively affect job satisfaction of natural gas workers. There is an additive interaction between psychological capital and social support on job ， satisfaction but no multiplicative interaction is found. Keywords: ； ； ； ； ； Psychological capital Social support Job satisfaction Interaction Natural gas Worker

OBJECTIVETo study the effects of intranigral injection of different doses of CuSO4.5H2O on dopaminergic neuron in the nigrostriatal system of rats.

METHODSWistar rats were divided into four groups, including control group, 10 nmol, 50 nmol and 200 nmol copper injected into left substantia nigra (SN) groups. Seven days after the intranigral injection of copper, dopamine (DA) contents in the striatum (Str) were measured by high performance lipid chromotophotography (HPLC); the density of tyrosine hydroxylase (TH) positive axons in the Str was measured by TH staining method; TH and Caspase-3 mRNA expression in the SN were measured by semi-quantitative RT-PCR. We detected the activity of superoxide dismutase (SOD) in the lesioned midbrain of rats using biochemical methods.

RESULTSDA and its metabolites contents had no significant difference between control group and low dose (10 nmol) copper group. But from 50 nmol copper group, DA contents in the lesioned sides were reduced with the increase in the copper doses injected, showing a significant linear correlation (F = 34.16, P < 0.01). In the 50 nmol copper group, TH positive axons in the Str decreased compared with those of the control and unlesioned sides (F = 121.9, P < 0.01). In the 50 nmol copper group, TH mRNA expression decreased (t = 3.12, P < 0.01) while Caspase-3 mRNA expression increased (t = 8.96, P < 0.01) in the SN compared with the control. SOD activity decreased in the midbrain of rats treated with 50 nmol copper compared with that of the control (t = 2.33, P < 0.01).

CONCLUSIONCopper could induce damage of dopaminergic neurons in the SN of rats through destroying antioxidant defenses and promoting apoptosis.

Animals ; Apoptosis ; drug effects ; physiology ; Axons ; drug effects ; metabolism ; pathology ; Caspase 3 ; drug effects ; genetics ; metabolism ; Copper ; toxicity ; Corpus Striatum ; drug effects ; metabolism ; pathology ; Dopamine ; metabolism ; Dose-Response Relationship, Drug ; Male ; Nerve Degeneration ; chemically induced ; metabolism ; pathology ; Neural Pathways ; drug effects ; metabolism ; pathology ; Neurons ; drug effects ; metabolism ; pathology ; Neurotoxins ; toxicity ; Oxidative Stress ; drug effects ; physiology ; Parkinsonian Disorders ; chemically induced ; metabolism ; physiopathology ; RNA, Messenger ; drug effects ; metabolism ; Rats ; Rats, Wistar ; Substantia Nigra ; drug effects ; metabolism ; pathology ; Superoxide Dismutase ; drug effects ; genetics ; metabolism ; Superoxide Dismutase-1 ; Tyrosine 3-Monooxygenase ; drug effects ; genetics ; metabolism ; Wallerian Degeneration ; chemically induced ; metabolism ; pathology

AIMTo prepare fluorescein sodium (FS) cationic liposomes and investigate the influence of cationic lipid (DC-chol) and polyethylene glycol (PEG) with different molecule weight (MW) on cationic liposome incorporation efficiency, cellular delivery and fluidity of liposome membrane.

METHODSUsing FS as a model material for encapsulation, the liposomes were prepared and separated (by sephadex G-50 1 cm x 20 cm column), and the liposome incorporation efficiencies was measured. The interaction between the FS and cationic liposomes was investigated by measuring the change of fluorescent spectrum. The cellular uptake of different liposome forms by choosing HepG2 2.2.15 as an in vitro cell culture assay model, and the influence of PEG on the fluidity of liposome membrane with the technique of fluorescence polarization were investigated.

RESULTSCationic lipid and different PEGs showed great effects on increasing liposome incorporation efficiency (from 0.64% to 86.57%), cellular uptake (from 2.18% to 48.46%) and fluidity of liposome membrane. The effect of PEG was MW dependent, and with the increase of MW, the incorporation efficiency and transfection was improved, and the fluidity of liposome membrane increased.

CONCLUSIONAddition of cationic lipid and high MW PEG into cationic liposomes can enhance the cellular delivery and fluidity of cationic liposomes. Also, they can improve the incorporation efficiency of cationic liposomes.

Cholesterol ; analogs & derivatives ; pharmacology ; Drug Delivery Systems ; Fluorescein ; Hepatoblastoma ; pathology ; Humans ; Liposomes ; Liver Neoplasms ; pathology ; Membrane Fluidity ; drug effects ; Molecular Weight ; Polyethylene Glycols ; chemistry ; pharmacology ; Transfection ; methods ; Tumor Cells, Cultured