Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Molecular Docking Simulation ; Molecular Structure ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; Quinazolinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

BACKGROUND:Negative pressure wound therapy has been widely recognized, the currently published papers are limited in academic value and lack of scientific, objective, qualified index to confirm the therapy effectiveness. OBJECTIVE:To systemical y evaluate the clinical effect of negative pressure wound therapy, provide more evidence for its clinical application, and guide clinical research.
METHODS:Fifteen articles were screened out of peer-reviewed publications (Cochran library, Embase, PubMed-Medline and Chinese BioMedical Literature Database). Scientific data were col ected and evaluated by two researchers. The data were statistical y analyzed with RevMan software.
RESULTS AND CONCLUSION:Only 15 random-control ed trials were final y preserved, including 10 as B-grade moderate bias risk and focused on the effect of negative pressure wound therapy on chronic wounds, and 5 as C-grade high bias risk and focused on the effect of negative pressure wound therapy on acute wounds. There were significant differences in the main outcome measures between negative pressure wound therapy and conventional wound therapy. As for chronic wound patients, no significant difference was observed in the operation-preparing period, reducing wound area, promoting wound granulation, and amputation rate between two therapies. As for acute wound patients, the differences were significant in the operation-preparing period, promoting wound granulation, wound infection rate, and cost materials between two therapies. However, no difference was significant in the healing of wound and hospitalization time. Our findings indicate that, negative pressure wound therapy is an effective means for both acute and chronic wounds, it can shorten operation-preparing period, promote wound granulation, and reduce amputation rate and infection rate, thus providing evidence for clinical application. The wel-designed study is needed to develop high-quality random control ed trails.

BACKGROUND:Negative pressure wound therapy has been extensively used, but most people only knew the superiority of negative pressure wound therapy based on clinical experiences or subjective judgment.
OBJECTIVE:To observe the effects of negative pressure wound therapy on the wound on the body surface, and to compare with contemporaneous conventional method.
METHODS:A total of 45 patients with wound on the body surface treated in the Peking Union Medical Col ege Hospital from January 2006 to December 2011 were enrol ed in this study, including 25 patients undergoing negative pressure wound therapy and 20 patients undergoing conventional change dressing method. Al clinical data were recorded.
RESULTS AND CONCLUSION:Negative pressure wound therapy was better than conventional method (P<0.05), on terms of preoperative preparation period, wound granulation, bacterial scavenging, labor intensity of working staff and incidence of postoperative complications. However, no significant difference in therapy cost was detectable (P>0.05). These results suggested that compared with conventional method, negative pressure wound therapy positively contributed to the healing, obviously shortened preoperative preparation, accelerated the diminution of wound, decreased the incidence of complications of reconstruction, lessened patient’s distress, reduced their economic cost, and diminished labor intensity of working staff. Negative pressure wound therapy has been proven an excellent tool of to promote wound healing.

Adult ; Female ; Humans ; Ki-1 Antigen ; metabolism ; Lymph Nodes ; metabolism ; pathology ; surgery ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; surgery ; Neck ; Receptor Protein-Tyrosine Kinases ; metabolism

To develop an oral drug,ITF gene encoding ITF proein,was expressed in a live delivery vehicle lactococcus lactis.First,the ITF gene was cloned into the prokaryotic expressive vector pNICE:sec.Second,the recombinant vector pNICE:sec-ITF was transformated into Lactococcus lactis strain NZ9000 to express ITF protein.Then the recombinant ITF was induced to express and was identified by SDS-PAGE and Western blot.Rabbits are divided into blank control group,preparation group and therapeutic group which are respectively administrated wih PBS and pNICE:sec-ITF Lactococcus lactis.By grades of ulcer test whether administrated pNICE:sec-ITF Lactococcus lactis protects against HCl-induced gastric injury in rabbits.The results were described as follows.The ITF was amplified and cloned in the vector pNICE:sec successfully.The fusion protein(5.9kDa) was expressed in L.lactis by the induction of the nisin.The quantity of expression accounted for 5% of the total bacterial protein.Western bolt analysis confirmed that fusion protein could be recognized specially by Monoclonal Anti-human TFF3 Antibody.Preparation groups and therapeutic groups do good than control group.Prove that administrated pNICE:sec-ITF Lactococcus lactis is biologically active in an HCl-induced rabbit gastric mucosal injury model.

Agroinfiltration is a newly developed plant transient gene expression technique, which is simple, rapid and reproducible. It has been widely used in analyses of foreign gene expression, hypersensitive reaction, gene silencing, promoter activity and identification of new disease-resistance genes. In this paper, we describe the principle and the operation procedure of Agroinfiltration and its application in diverse aspects of plant molecular biology research. Our experiences in modification of the Agroinfiltration technique are also provided.
Agrobacterium tumefaciens ; genetics ; Genetic Vectors ; genetics ; Plants ; genetics ; Plants, Genetically Modified ; Research Design

OBJECTIVETo compare the effect of transumbilical single-site single-port with that of transumbilical single-site double-port laparoscopic varicocelectomy in the treatment of varicocele in adolescents.

METHODSWe randomly assigned 80 varicocele patients aged 10 - 16 years to two groups of equal number to receive transumbilical single-site single-port and single-site double-port laparoscopic varicocelectomy, respectively. We compared the operation time, postoperative hospital stay, incisional pain, complications and satisfaction with the abdominal cosmetic outcomes between the two groups.

RESULTSAll the operations were successfully performed. The double-port group showed a significantly higher score on the Visual Analogue Scale than the single-port group (4.8 +/- 1.4 vs 3.6 +/- 1.1, t = -4.986, P < 0.01), but there were no significant differences between the two groups in the operation time ([29.8 +/- 4.2] vs [31.2 +/- 4.6] min, t = 1.383, P = 0.171), postoperative hospital stay ([1.95 +/- 0.7] vs [1.82 +/- 0.8] d, t = -0.784, P = 0.436), complications (0 vs 0) and scores on the satisfaction with abdominal cosmetic outcomes (4.6 +/- 0.6 vs 4.8 +/- 0.5, t = 1.253, P = 0.214). No recurrence, umbilical hernia, hydrocele and orchiatrophy were found in the two groups of patients at 6 months after operation, and no visible scar was observed on the abdominal surface.

CONCLUSIONWith strict surgical indications, single-site single-port and single-site double-port laparoscopic varicocelectomies have similar clinical effects in the treatment of varicocele, which leave no scar on the abdominal surface. Single-site double-port laparoscopy needs no special instruments and therefore is worthier of wide clinical application.

Adolescent ; Child ; Humans ; Laparoscopy ; methods ; Length of Stay ; Male ; Operative Time ; Umbilicus ; surgery ; Varicocele ; surgery

Objective To study the change of vascular endothelial growth factor(VEGF) in myocardial tissue and serum of myocardial ischemia in rats.Methods Twenty SD rats were randomly divided into normal control group and test group. Test group was ligated coronary artery,and the control group was pulled on line but not ligated,then observed the change of VEGF.The histological and immunohistochemical method were used for observing the change of VEGF serum in myocardial ischemia in rats' heart.VEGF levels were measured by image analysis.Results Compared with control group,the expression of VEGF in the myocardial ischemia group was increased obviously(P

Objective To evaluate the damage caused by high intensity ultrasound(HIU)on tumor micro- vessels.Methods Rabbit models of the VX_2 tumor were set up.The target hepatic carcinomas were treated with HIU,and the results were observed using hematoxylin-eosin(HE)staining,vascular endothelial cell biotinylated-ulex europaeus agglutininiⅠ(UEAI)immunohistochemical staining,tumor micro-vessel counts,and electron microscopy. Results Histological examination through HE staining indicated that HIU induced carcinoma vascularities with whole tumor tissue coagulative necrosis.The UEAI immunohistochemical staining of the target lesions treated by HIU was ne- gative,and complete tumor micro-vessel uhrastructure damage was observed under the electron microscope.Conclu- sion HIU can damage tumor micro-vessels thoroughly,in such way that it may inhibit tumor growth and metastasis.

OBJECTIVETo analyze retrospectively the postoperative complications of acromioclavicular joint dislocation (Tossy III) and explore the preventative methods for the complications.

METHODSForty-eight cases of acromioclavicular joint dislocation (Tossy III) were reviewed, 14 cases treated with open reduction and Kirschner wire combined with steel wire fixation (group A), 11 cases treated with open reduction and lag screw or steel wires fixation (group B), 23 cases treated with open reduction and AO clavicular hook plate fixation (group C). The acromioclavicular ligament, articular capsule, coracoclavicular ligament and coracoacromial ligament were repaired in all patients. The reasons of postoperative complications were analyzed.

RESULTSForty-eight patients got average follow-up of 18 months. In group A, 8 patients obtained excellent results, 4 good and 2 poor; in group B, 7, 3 and 1, respectively; in group C, 21, 1 and 1, respectively. The excellence rate showed statistical difference between group A and C (P < 0.05). In group A, 4 cases with postoperative pain, 3 cases with periarthritis of shoulder, 3 cases with arthritides of acromioclavicular joint, 4 cases with internal fixation failure and 2 cases with recurrence of joint dislocation; in group B, 3, 2, 1, 3 and 1, respectively; in group C, 22, 2, 1, 2 and 1, respectively. There was no significant difference in postoperative complications in three groups (P > 0.05).

CONCLUSIONSelection of the suitable internal fixation and reconstruction of coracoclavicular and coracoacromia ligaments is the basic operation. Acromioclavicular space debridement, ligamentous reconstruction, rigid internal fixation are effective methods to reduce postoperative complications for the treatment of acromioclavicular joint dislocation.

Acromioclavicular Joint ; injuries ; surgery ; Adolescent ; Adult ; Bone Plates ; Bone Screws ; Bone Wires ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Male ; Middle Aged ; Postoperative Complications ; etiology ; prevention & control ; Retrospective Studies ; Shoulder Dislocation ; complications ; surgery ; Young Adult