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

Objective To summarize our experience in prevention and treatment of stricture after esopageal burns in the past thirty years.Methods There were 168 cases in this series.Of them,158 cases underwent surgical management in this study.Modified intraluminal stenting was used in 34 cases, colon interposition without resection of strictured esophagus in 77 cases,gastric transposion with resection of the stricture in 27,repair of cervical stricture with platysma myocutaneous flap in 22,and miscellane- ous operation in 12.Eleven cases experienced operation twice or more at our department.Results Twenty-nine cases recovered after treatment with intraluminal stenting,and 5 re-experienced stricture after stent removal.One of the 5 cases with failed stent responded to bougienage,and the remaining 4 cases re- quired esophageal reconstruction later.Of the 77 colon interpositions,5 cases died postoperatively,and complications of cervical anastomotic fistula occurred in 14 cases,anastomotic stenosis in 4,and abdomi- nal incision dehiscence in 2 cases.In the 27 cases with gastric transpositions,postoperative complications of anastomotic stricture occurred in 2 cases and empyema in 1 patient.There was a cervical leak in 3 ca- ses of the 22 cases treated with the repair of cervical esopageal or anastomotic stricture with a platysma myocutaneous flap.In the 12 cases treated with miscellaneous operation,one died of intestinal obstruc- tion.All the survivors had regular diet after discharge.Conclusions Intraluminal stenting can prevent the formation of caustic esophageal stricture.The location of the cicatricial esophagus dictates whether to perform concomitant esophagectomy during esophageal reconstruction.Platysma myocutaneous flap repair is an excellent method for the treatment of severe cervical esophageal or anastomotic stricture.

Objective To study the role of hematopoietic growth factor(HGF)of placenta chorionic villus in fetal hematopoiesis during embryo ontogeny by observation of the appearance time and the content changes with the fetal growth, which was compared with HGF in cord blood. Methods Thirty embryo villus (2 g each) and 30 cord blood (2 mL each) were collected separately from early pregnant stage(6- 8 weeks), middle pregnant stage(16-22 weeks)and late pregnant stage (37-42 weeks). The levels of HGF were detected by enzyme - linked immunosorbent assay. Results HGF were produced on the early pregnant stage and the content of FL-T3,IL-3 increased gradually.There were significantly differences at different stages(P

OBJECTIVETo investigate the efficacy of repeat transurethral resection of tumor in patients with non-muscle invasive bladder cancer.

METHODSFrom March 2004 to August 2008, 462 patients (350 males, 112 females, aged from 35 to 83 years old) with non-muscle invasive bladder cancer, were evaluated according to tumor stage, grade and muscle or no muscle tissue in initial transurethral resected sample. One hundred and twenty-five patients underwent repeat transurethral resection of bladder tumor within 4 to 6 weeks after initial resection. Of these 125 patients 49 were Ta, 76 were T1, 58 were low grade carcinoma, 67 were high grade carcinoma and 30 were not found presence of muscle tissue in initial resected sample in patients with T1 stage.

RESULTSOf the 125 cases, 34.4% (43/125) had residual tumor and 65.6% (82/125) had no tumor on repeat transurethral resection. Of 43 cases with residual tumor 35 had non-muscle invasive tumor including 15 in Ta and 20 in T1. The patients with high grade carcinoma had more residual tumor than those with low grade carcinoma (P < 0.05). The patients with muscle tissue in initial transurethral resected sample had fewer residual tumor than those without (P < 0.05). Twelve cases (9.6%) were understated at initial resection. Six cases (4.8%) had bladder perforation and 7 (5.6%) had bleeding during repeat transurethral resection. All cases were followed up for 3 to 56 months (median 26 months), 37.2% (16/43) patients with residual tumor in repeat transurethral resection had recurrence while only 12.2% (10/82) without residual tumor in repeat transurethral resection did (P < 0.05).

CONCLUSIONSRoutine repeat transurethral resection is advised to non-muscle invasive bladder cancer patients with T1 tumor or high grade carcinoma or no muscle tissue in initial transurethral resected sample within 4 to 6 weeks after initial resection. Repeat transurethral resection could increases the stage accuracy.

Adult ; Aged ; Aged, 80 and over ; Electrosurgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Reoperation ; Retrospective Studies ; Treatment Outcome ; Urinary Bladder Neoplasms ; surgery ; Urologic Surgical Procedures ; statistics & numerical data

OBJECTIVETo establish an animal model of traumatic optic neuropathy (TON) that resemble to clinical state and study the mechanical principle and change of pathophysiology of its nerve injury for clinical diagnosis and treatment.

METHODSNew Zealand white rabbits were used as the research objects. The method introduced by Wang Yi was repeated and improved. Mild and severe animal models of TON were established by reformed Wang Yi operation separately. After the spring gun struck, all animals were observed on pupils and direct light reflex and received the examinations of pattern reversal visual evoked potentials (PR-VEP). The pathophysiology of normal and injury optic nerve was observed.

RESULTSAfter recovery from anesthesia, the mydriasis and disappearance or dullness of direct light reflex happened in all injured eyes. No brain contusion, infection, orbital fracture and death were found. One optic nerve was broken with complete tunica vaginalis. The latency and amplitude of injured eyes deteriorated gradually. In group B, the waves became flat rapidly. After injury, the optic nerve underwent 3 stages: edema, hyperplasia and atrophy. The pathomorphological changes of injured eyes in group B were more serious than that in group A in any time.

CONCLUSIONSThe reformed operation can establish constant nerve injury with high success rate. In mildly injured eyes, the injury deteriorated gradually. However, part visual function remained. In severely injured eyes, the pathomorphological changes were irreversible sooner after struck, and the visual function lost completely. There is a good correlation between PR-VEP and pathomorphology. PR-VEP can guide the clinical diagnosis and treatment.

Animals ; Evoked Potentials, Visual ; Male ; Models, Animal ; Optic Nerve ; physiopathology ; Optic Nerve Injuries ; physiopathology ; Rabbits

OBJECTIVETo introduce a method by reversed ulnar fasciocutaneous flap incised form the ulnar side of the fifth metacarpal area for repairing the soft tissue defect of the fifth finger.

METHODSFrom May 2001 to September 2001, ten patients with the soft tissue defects of the thenar side, dorsal side or ulnar side of the fifth finger were treated with the reversed ulnar fasciocutaneous flap incised from the fifth metacarpal area. The axial line of the flap was the line from ulnar side of the head of the fifth metacarpal bone to the pisiform level. The revolving point of the flap pedicle was 0.5-1 cm near the proximal end of the metacarpal-phalangeal joint.The area of the flap was form 5.0 cm x 3.5 cm to 1.5 cm x 1.0 cm.

RESULTSAll flaps of the ten cases were alive. 5-7 months followed-up show that, after operation, the flap present sensation in 6-12 mm, with soft texture and good appearances.

CONCLUSIONSThe advantages of this operative method were as follows: the reversed ulnar fasciocutaneous flap of the fifth metacarpal area have reliable blood supply, it was easily dissected and with good texture. So far this kind of flap is a good choice in repairing the soft tissue of the fifth finger.

Adolescent ; Adult ; Fascia ; transplantation ; Female ; Finger Injuries ; surgery ; Humans ; Metacarpal Bones ; surgery ; Middle Aged ; Reconstructive Surgical Procedures ; Soft Tissue Injuries ; surgery ; Surgical Flaps ; Young Adult

OBJECTIVETo investigate the effect of cytosine deaminase (CD) gene plus 5-fluorocytosine (5-Fc) on the growth of human colon cancer xenograftin nude mice.

METHODSRetroviral vector expressing CD gene was transfected into human colon cancer SW1116 cells. Expression of the transfected CD gene in SW1116 (SWCD(2)) was confirmed by RT-PCR. The cytotoxicity of 5-Fc on SW1116 was determined by MTT assay in vitro. In vivo, the CD gene expression vector was injected intratumorally and 5-Fc was given by ip injections.

RESULTSIn vitro, SWCD(2) cells were killed by 5-Fc with an IC(50) of 66 micromol/L while the nontrasfected SW1116 cells needed an IC(50) of 16 000 micromol/L to be killed. The growth of SWCD(2) xenografts was significantly inhibited by systemic administration of 5-Fc.

CONCLUSIONCD gene/5-Fc system is a potential gene therapy strategy for human colon cancer.

Animals ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Colonic Neoplasms ; metabolism ; pathology ; prevention & control ; Combined Modality Therapy ; Cytosine Deaminase ; genetics ; metabolism ; Female ; Flucytosine ; pharmacology ; therapeutic use ; Genetic Therapy ; Genetic Vectors ; Humans ; Inhibitory Concentration 50 ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Retroviridae ; genetics ; Transfection

OBJECTIVETo assess the clinical effect and safety of the Chinese medicine Longbishu Capsule combined with mesylate doxazosin in the treatment of benign prostatic hyperplasia (BPH) of the kidney deficiency and blood stagnation type.

METHODSThis was a randomized, double-blind, double-simulation control study. We equally assigned 60 men diagnosed with BPH of the kidney deficiency and blood stagnation type to an experimental and a control group, the former treated with mesylate doxazosin plus Longbishu Capsule and the latter with mesylate doxazosin plus placebo. We compared the International Prostate Symptom Score (IPSS), quality of life (QOL), Chinese symptom score (CSS), maximal urinary flow rate (Qmax), and prostate volume between the two groups of patients before and after 6 months of medication.

RESULTSAfter treatment, there were 5 cured cases, 13 markedly effective cases, 9 effective cases, 1 ineffective case, and 2 eliminated cases in the experimental group, as compared with 2 cured cases, 8 markedly effective cases, 10 effective cases, 7 ineffective cases, and 3 eliminated cases in the control group. The total effectiveness rate was obviously higher in the former (96.4%) than in the latter (74.1%). IPSS, Qmax, and CSS were improved in both of the groups after medication, even more significantly in the experimental than in the control group (IPSS: 15.22 ± 2.98 vs 18.15 ± 5.88, P <0.05; Qmax: [13.56 ± 2.26] ml/s vs [11.78 ± 2.97] ml/s, P <0.05; CSS: 6.18 ± 2.13 vs 9.52 ± 3.15, P <0.05). Because of the difference in the QOL score between the two groups at the baseline (P = 0.038 <0.05), no more comparison was made in this aspect after treatment.

CONCLUSIONThe combination of Longbishu Capsule with mesylate doxazosin is safe and effective for the treatment of BPH.

Adrenergic alpha-Antagonists ; therapeutic use ; Capsules ; Double-Blind Method ; Doxazosin ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Male ; Prostatic Hyperplasia ; drug therapy ; physiopathology ; Quality of Life ; Treatment Outcome ; Urination

OBJECTIVETo observe the effects of Qiangjing Tablets (QJT) on the semen quality and Fas/FasL signaling pathway in male SD rats with infertility.

METHODSModels of infertility were made in 50 male SD rats by intragastric administration of Tripterygium (GTW) for 3 weeks, and another 20 rats were taken as blank controls. Then 40 successfully established rat models were randomly divided into four groups, model control, low-dose QJT, medium-dose QJT, and high-dose QJT, the latter three groups treated intragastrically with QJT at 58 mg, 105 mg, and 233 mg per kg of the body weight per day, respectively. After 4 weeks of medication, the rats were killed for examination of semen quality and determination of the expression of the apoptosis factor FasL in the testis tissue.

RESULTSCompared with the blank controls, the model rats showed significant decreases in sperm concentration ([71.99 ± 9.72] vs [10.94 ± 3.58] x 10⁶/ml, P < 0.01), motility ([48.95 ± 4.10] vs [9.31 ± 5.79]%, P < 0.01), and viability ( [82.06 ± 6.16] vs [24.03 ± 6.93]%, P < 0.01). In comparison with the model controls, the rats in the QJT groups exhibited remarkably increased sperm concentration, motility, and viability, more significantly in the high-dose group ([59.66 ± 4.53] x 10⁶/ml, [35.45 ± 5.21] %, and [61.97 ± 9.75]%) and medium-dose group ([40.89 ± 4.90] x 10⁶/ml, [24.41 ± 4.79]%, and [60.06 ± 10.62]%) (P < 0.05 or P < 0.01). The expression of FasL was markedly reduced in the low-, medium-, and high-dose QJT groups (0.5215 ± 0.0189, 0.5371 ± 0.0364, and 0.4556 ± 0.0215) as compared with that of the model controls (0.5989 ± 0.0448 ) (P < 0.05 or P < 0.01).

CONCLUSIONBy upregulating the Fas/FasL signaling pathway, Tripterygium glycosides may induce the apoptosis of spermatogenic cells and reduce sperm concentration, motility and viability, resulting in infertility. The Chinese medicine Qiangjing Tablets can improve the reproductive function of male rats by decreasing the expression of the apoptosis factor FasL in the testis.

Animals ; Apoptosis ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Fas Ligand Protein ; drug effects ; metabolism ; Germ Cells ; Glycosides ; Infertility, Male ; chemically induced ; drug therapy ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Semen ; drug effects ; Semen Analysis ; Signal Transduction ; Sperm Count ; Sperm Motility ; drug effects ; Tablets ; Testis ; drug effects ; metabolism ; Tripterygium