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

OBJECTIVETo investigate the influence of GC Initial Ti Bonder on bond strength between Vita Titankeramik porcelain and titanium.

METHODSForty titanium samples were prepared and randomly assigned to 4 groups with 10 samples in each group. Samples in each group were subjected to one of the following surface treatments, burnishing (Group B), sandblasting (Group S), firing GC Initial Ti Bonder after burnishing (Group BG) and firing GC Initial Ti Bonder after sandblasting (Group SG). Vita Titankeramik porcelain were fired on the surface of each sample in the middle. Three-point bending tests were conducted on each sample according to the ISO 9693. The fracture patterns of all specimens were recorded using zoom stereo microscope (ZSM) and the fracture surfaces were observed under scanning electron microscope (SEM).

RESULTSWith fired GC Initial Ti Bonder, the bond strength of Vita Titankeramik porcelain to titanium in Group BG and Group SG were (32.72 +/- 4.46) and (34.25 +/- 6.52) MPa respectively, which reach the ISO 9693 standard for clinical use and were significantly higher than those in Group B [(20.70 +/- 3.15) MPa] and Group S [(23.92 +/- 5.02) MPa].

CONCLUSIONSGC Initial Ti Bonder can significantly improve bond strength between Vita Titankeramik porcelain and titanium.

Dental Bonding ; Dental Porcelain ; chemistry ; Dental Stress Analysis ; Humans ; Materials Testing ; Microscopy, Electron, Scanning ; Surface Properties ; Titanium ; chemistry

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.

AIM:To observe the efficacy of intravitreal conbercept injection for chronic central serous chorioretinopathy (CSC).METHODS: Nine eyes of 9 patients diagnosed as chronic CSC between October 2015 to May 2016 were treated with an intravitreal injection of conbercept (0.5mg/0.05mL) (six patients were given the same does of intravitreal injection again at 1mo after the first injection).Follow-up observation was at 1, 2, and 6mo after injection.Observed indicators included best-corrected visual acuity (BCVA), intraocular pressure, optical coherence tomography (OCT), fundus fluorescein angiography (FFA), choroidal indocyanine green angiography (ICGA), macular fovea thickness (CMT), subfoveal choroidal thickness (SFCT).RESULTS:Seven of the 9 patients responded significantly to the drug, while 2 patients had no response.The CMT was 373.12±72.43μm at baseline, which decreased significantly to 332.05±67.13μm, 282.24±62.30μm and 225.56±71.08μm at 1, 2 and 6mo after the intravitreal injection.The mean thickness of SFCT was 422.11±64.82μm before treatment.The choroidal thickness of non-responsive patients before treatment was below average, respectively 353μm and 365μm.The SFCT of 1, 2, and 6mo after treatment was 391.45±75.24μm, 365.53±63.07μm, 355.40±66.65μm.Before treatment and 1mo after, there was no significant difference (P=0.074), but there was statistically significant (P<0.01) between those of before and 2mo and 6mo after.The mean BCVA of the prior treatment was 0.53±0.32, the after treatment was 0.65±0.20, there was no different between the two(P>0.05).CONCLUSION: Intravitreal conbercept injection in chronic CSC may have some effect in accelerating subertinal fluid resolution and decreasing the CMT.The SFCT within 6mo after treatment was significantly lower than pretreatment.The SFCT may be an indicator of whether patients respond.

OBJECTIVETo establish a liquid chip technology to detect Y chromosome microdeletions in Chinese infertile males with azoospermia or oligozoospermia.

METHODSMultiplex PCR and liquid chip technology were used to detect the Y chromosome microdeletions in AZF region in 178 infertile patients with azoospermia and 134 infertile patients with oligozoospermia as well as 40 fertile control men.

RESULTSForty out of 312 patients (12.8%) were found to have deletions in AZF region. The microdeletion frequency was 14%(25/178) in the azoospermic group, 9.6%(11/114) in the oligospermic and 20%(4/20) in the severe oligospermic group.

CONCLUSIONThe authors developed a high-throughput, fast and simple assay to screen the AZF region microdeletions of Y chromosome.

Asian Continental Ancestry Group ; genetics ; Azoospermia ; genetics ; Base Sequence ; Chromosome Deletion ; Chromosomes, Human, Y ; genetics ; Electrophoresis, Polyacrylamide Gel ; Humans ; Male ; Oligonucleotide Array Sequence Analysis ; methods ; Oligospermia ; genetics ; Sequence Tagged Sites

OBJECTIVETo observe the regulatory effect of Bushen Jianpi Recipe (BSJPR) on cellular immunity the of primary liver cancer patients of Gan-Shen yin-deficiency and Pi qi-deficiency syndrome type after intervention therapy.

METHODSAccording to the multi-center randomized controlled principle, 117 patients after transcatheter arterial chemoembolization (TACE) were assigned to two groups, 60 in the treated group and 57 in the control group, who were treated respectively with BSJPR and liver protecting remedy (silymarin and vitamin c) for 12 weeks. Changes in TCM syndrome, quality of life (QOL), immediate effect on tumor size and survival time were observed. Meantime, the cellular immune function was also observed, including the T lymphocyte response determined by 3H-TdR, expression of MHC class I/II and B7 molecule detected by FACS, and interleukin 10 and 12 (IL-10, IL-12), interferon-gamma (IFN-gamma) tested by ELISA.

RESULTSIn the treated group after treatment, the efficacy for improving TCM syndrome reached 73.33% (44/60 cases), their half-year survival rate being 83.33% (50/60 cases); while those in the control group were 52.63% (30/57 cases) and 70.18% (40/57 cases) respectively, significant difference was shown between the two groups (P <0.05). The patients' QOL was improved in the treated group after treatment, with no obvious adverse reaction. However, the clinical benefit rate in the control group (92.7%, 51/55 cases) was higher than that in the treated group (78.0%, 46/59 cases, P =0. 035). Laboratory examination showed increases of MHC class II (CD14+/HLA-DR) expression on monocyte surface as well as IFN-gamma and IL-12 production in the treated group.

CONCLUSIONUsing BSJPR together with TACE could enhance patients' cellular immune function to elevate the clinical curative effect on primary liver cancer.

Adult ; Aged ; Ascorbic Acid ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Liver Neoplasms ; drug therapy ; immunology ; Male ; Middle Aged ; Silymarin ; therapeutic use ; T-Lymphocytes ; drug effects ; immunology ; Treatment Outcome

Genotypic and environmental variation in Cd, Cr, As, Ni and Pb concentrations of grains, and the relationships between these heavy metals and Fe, Zn were investigated using 9 rice genotypes grown in 6 locations for two successive years. Significant genotypic variation was detected in the five heavy metal concentrations in grains, indicating the possibility to reduce the concentration of these heavy metals in grains through breeding approach. The environmental effect varied with metal, with Pb and Ni having greater variation than the other three metals. There was significant genotype-environment (location) interaction of the concentrations of all five heavy metals in grains, suggesting the importance of cultivar choice in producing rice with low heavy metal concentrations in grains for a given location. Correlation analysis showed that Cd and As, Cr and Ni, and As and Pb concentrations in rice grains were closely associated, and that Ni concentration in grains was negatively correlated with Zn concentration.
Arsenic ; analysis ; Cadmium ; analysis ; Chromium ; analysis ; Edible Grain ; chemistry ; genetics ; Environment ; Genetic Variation ; genetics ; Genotype ; Lead ; analysis ; Metals, Heavy ; analysis ; Nickel ; analysis ; Oryza ; chemistry ; genetics ; Soil Pollutants ; analysis

OBJECTIVETo investigate the prevalence of malignant tumor and its influencing factor among rubber workers in Hainan Province of China, and to study the high incidence of cancer and type of work.

METHODSA retrospective cohort study on registered workers over 1 working age among partial rubber factories in Hainan Province in the period from 2005 to 2010.

RESULTThere was a remarkable difference in the incidence between nature exposed rubber group and non-exposed group (χ(2) = 52.13,P < 0.01). Occupational exposure induced a high risk in malignant tumors (OR = 2.47, P < 0.05). The incidence of tumor may be associated with occupational exposure: the longer occupational exposure time, the higher was the incidence of tumor (χ(2) = 11.40, P < 0.05).

CONCLUSIONSThe occupational exposure in rubber workers can induce a high incidence of malignant tumor.

China ; epidemiology ; Female ; Humans ; Male ; Neoplasms ; epidemiology ; Occupational Exposure ; Prevalence ; Risk Factors ; Rubber

OBJECTIVETo observe the effects of electroacupuncture (EA) on circadian rhythm of temperature and melatonin (MT) in depression rats model induced by chronic stress, so as to explore the biological mechanism of EA for depression.

METHODSTwenty-four SD rats were randomly divided into a control group, a model group and an EA group, 8 cases in each one. Rats in the control group were treated with normal diet for 21 days without any treatment. In the model and EA group, rat model was established by chronic unpredictable stress combined with solitarily feeding method, and rats in the EA group was treated with EA at "Baihui" (GV 20), "Yintang" (GV 29) 1 h before stress stimulation everyday, 2 Hz in frequency and intensity was favorable with the head of rat slightly shivering. The needles were retained for 20 min, once a day for totally 21 days. After EA treatment, open-field experiment was adopted to observe the behavioral improvement; the rats temperatures were monitored at six time points (2:00, 6:00, 10:00, 14:00, 18:00, 22:00) and orbital blood sampling was collected. The level of serum MT was tested by enzyme linked immunosorbent assay. The circadian rhythm changes of temperature and serum MT in each group were compared.

RESULTSThe numbers of horizontal movement and vertical movement in the model group were obviously lower than those in the control group (both P < 0.05), while those in the EA group were significantly improved compared with those in the model group (both P < 0.01). The circadian rhythm of temperature and MT disappeared in the model group, which was improved into normal level after EA treatment.

CONCLUSIONThe electroacupuncture has regulation effects on circadian rhythm of temperature and melatonin in depression rat model induced by chronic stress.

Animals ; Circadian Rhythm ; Depression ; metabolism ; physiopathology ; therapy ; Electroacupuncture ; Humans ; Male ; Melatonin ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate results of total knee arthroplasty using the long-stem tibial component combined with metallic wedge of knee prosthesis for the treatment of proximal defects.

METHODSFrom January 2011 to May 2013, 10 patients (11 knees) were treated with total knee arthroplasties using the long-stem tibial component with metallic tibial wedge of knee prosthesis. All the patients were female and the average age was 67 years old (ranged, 60 to 77 years old). All the patients were osteoarthritis. All the patients were classified as T2A style. The patients were evaluated according to knee score system (KSS).

RESULTSAll the patients were followed up for 12 months on average (ranged 3 to 29 months). The clinical outcome was assessed using KSS score, including knee pain score, knee stability score, knee range of motion score and knee walking score, knee stairs score. There were significantly differences at 6 weeks, 3 months, 6 months and 12 months between pre-and postoperative KSS score.

CONCLUSIONThe mechanical stability of tibial fixation in primary TKA is significantly increased by using the long-stem tibial component with metallic wedge of knee prosthesis, even in the presence of poor proximal bone.

Aged ; Arthroplasty, Replacement, Knee ; Female ; Humans ; Knee Joint ; physiopathology ; surgery ; Knee Prosthesis ; Male ; Osteoarthritis, Knee ; physiopathology ; surgery ; Range of Motion, Articular ; Tibia ; abnormalities ; physiopathology ; surgery