PARP [poly(ADP-ribose)polymerase] represents a novel potential target in cancer therapy. It is involved in a DNA repair process by catalyzing the transfer of ADP-ribose units from NAD to a number of its substrate proteins. In this work, a series of novel azaindole derivatives was designed and synthesized. Moreover, 16 target molecules were screened and 8 compounds displayed inhibitory activity against PARP-1. It has been demonstrated that these azaindoles bearing cycloamine substituents at 2-position were active to both PARP-1 and PARP-2.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Aza Compounds ; chemical synthesis ; chemistry ; pharmacology ; Indoles ; chemical synthesis ; chemistry ; pharmacology ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; metabolism

Background Porcine fibrin sealant kit has been widely used in surgery for clotting and woundssealing.It is thought to be a substitution for inert gas and silicone oil in vitrectomy.But whether it produce toxic effect on retina or not after intravitreal injection is still studying.Objective This study aimed to investigate the retinal toxicity of porcine fibrin sealant kit following intraocular application.Methods Vitrectomy was performed on bilateral eyes of 15 pigmented rabbits.Porcine fibrin sealant kit of 0.5 ml was intravitreally injected in the lateral eyes of the rabbits as the experimental group,and equal volume of BSS was used at the same way in contralateral eye as control group.The inflammatory response of eye was observed under the slit lamp and ophthalmoscopy in 1 day,3,7,15,30 days after injection.Schi(o)tz tonometer was used to measure intraocular pressure(IOP) in 1 day,3,7 days,and retinal function was evaluated by electroretinogram (ERG) before operation and 30 days after operation.B-ultrasonic examination was carried out 30 days after surgery.Animals were sacrificed and eyeballs were obtained for retinal histopathological and ultrastructural examination in 30 days after operation.Results Complications appeared in 7 eyes of the experimental group,including cataract in 3 eyes,proliferation vitreoretinopathy and retinal detachment in 5 eyes,endophthalmitis in 1 eye,however,the cataract in 2 eyes and retina injury in 2 eyes were found in 15 control eyes.On the 30 days after injection,no inflammation was found in the 8 eyes without complication in the experimental group and 11 eyes in the control group.The IOP change was insignificant in different groups and various time points (Fgroup =0.008,P =0.929 ;Ftime =3.600 P =0.075).No significant difference was found in a-wave amplitude between groups and various time points(Fgroup =0.728,P =0.405 ; Ftime =0.516,P =0.482),and so was the b-wave amplitude (Fgroup =0.222,P =0.644 ; Ftime =0.057,P =0.814).On the 30th day after operation,arrangement of the retina was regular and no tissue edema and inflammatory cell infiltration were seen in both groups under the light microscope.Transmission electron microscope revealed that the ultrastructures of retinal cells,photoreceptor and retinal pigment cell were normal with the clear subcellular organelle,intact cellular membrane structure and mitochondria in both groups.Conclusions Domestic porcine fibrin sealant kit does not produce toxic effect on retina after intravitreal injection in rabbit.

OBJECTIVETo investigate the functional reconstruction technique for partial lower lip defects.

METHODS7 patients with lower lip cancer (3 cases of basal cell carcinoma, 2 cases squamous cell carcinoma and 2 cases papillary carcinoma) underwent excision. The full-thickness lower lip defects were one-third to two-third of the total lower lip length. All the defects were reconstructed with V-Y island advancement flaps based on the mental neurovascular bundle.

RESULTSThere was no flap loss. No recurrence was observed during the follow-up period of 3 months to one year. Both the aesthetic appearance, muscle function and sensation of the reconstructed lower lip were satisfactory.

CONCLUSIONSMental neurovascular V-Y island advancement flap is an ideal method for functional repair of partial lower lip defect.

Aged ; Carcinoma, Basal Cell ; surgery ; Chin ; innervation ; Female ; Humans ; Lip ; injuries ; Lip Neoplasms ; surgery ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Surgical Flaps ; blood supply

The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bile Acids and Salts ; metabolism ; Bilirubin ; blood ; Chemical and Drug Induced Liver Injury ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Fallopia multiflora ; chemistry ; HMGB1 Protein ; metabolism ; Hepatocytes ; drug effects ; Interleukin-1beta ; metabolism ; Liver ; drug effects ; pathology ; Plant Extracts ; pharmacology ; Rats ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the ultrasonographic features of congenital intrahepatic portosystemic venous shunt (CIPSVS) and to assess the clinical value of ultrasonography in the diagnosis of CIPSVS.

METHODSSix cases of CIPSVS diagnosed in our hospital between March 2010 and March 2012 and confirmed by enhanced computed tomography (CT) were retrospectively reviewed. Five of the six cases had follow-up data that was included in the analysis.

RESULTSAmong the six CIPSVS cases, only one was classified as Park's type II and the rest were classified as Park's type III. Five cases involved the right lobe of the liver and only one case involved the left lobe. The lesion shapes included cystic, tubular, and irregular with clear contour and appeared to be anechoic on CT scan. The lesions ranged in size from 1.1*0.6 cm to 2.0*1.7 cm. For all cases, the color Doppler ultrasound images showed blood flowing from the portal vein to the hepatic vein, and single-phase spectrum was detected in the diversion channel. The differences observed in level of lesion size and blood flow velocity at the shunt from the time of examinations at diagnosis and subsequent follow-up did not reach statistical significance (P = 0.223 more than 0.05 and P = 0.930 more than 0.05 respectively).

CONCLUSIONAlthough cases of CIPSVS are rare, they share some specific sonographic features that may help in diagnosis. Color Doppler ultrasound findings have high diagnostic accuracy and may represent a preferred modality for follow-up monitoring.

Aged ; Female ; Humans ; Male ; Middle Aged ; Portal Vein ; abnormalities ; diagnostic imaging ; Retrospective Studies ; Ultrasonography ; Vascular Malformations ; diagnostic imaging

BACKGROUNDCoronary computed tomographic angiography (CCTA) has been widely used in patients who are at intermediate risk for having stable coronary artery disease (SCAD), and 2013 European Society of Cardiology Guidelines on the Management of SCAD (2013G) recommended the appropriate application of CCTA. However, 2013G has not been subjected to systematic analyses for subsequent impact on clinical practice.

METHODSA total of 5320 patients suspected with SCAD were enrolled and scheduled for CCTA from March 2013 to September 2014. For each patient, pretest probability of SCAD was calculated according to updated Diamond-Forrester model (UDFM). Appropriate CCTA or appropriate stress test was determined as described in the 2013G. A generalized estimating equation model was used to determine the trends in the half-monthly rate of appropriate CCTA.

RESULTSOverall, only 61.37% of patients received appropriate CCTA, and there was insignificant change over time (P = 0.8701). The application of CCTA in patients who should have had a stress test accounted for most of the inappropriate CCTA before (22.29%) or after (19.98%) the publication of the 2013G. In all patients or any subgroup, no significant change in the adjusted half-monthly rate of appropriate CCTA was found after the publication of the 2013G (odds ratio, 1.002; 95% confidence interval, 0.982-1.021; P = 0.8678).

CONCLUSIONSThese findings suggest that the 2013G have not, to date, been fully incorporated into clinical practice, and the clinical utilization of CCTA remains unreasonable to some extent.

Aged ; Coronary Angiography ; methods ; Coronary Artery Disease ; diagnosis ; Female ; Humans ; Male ; Middle Aged ; Odds Ratio

OBJECTIVETo demonstrate molecular characterization of a newly isolated enterovirus.

METHODSVirus were isolated from patient with unknown-causing disease and tested by reverse transcription-polymerase chain reaction (RT-PCR) and 5'3'RACE (rapid amplification of cDNA ends, RACE), in an attempt to obtain the sequence of this newly isolated enterovirus.

RESULTSSequence analysis showed that this newly isolated enterovirus shared 83%-94% nucleotide identity and 91%-100% amino acid identity with enterovirus 89. Phylogenetic analysis indicated that it was probably a new subtype of enterovirus 89.

CONCLUSIONThis newly isolated enterovirus in the stool specimen from patient has the same serotype with enterovirus 89, but it was probably a new subtype of enterovirus 89.

Amino Acid Sequence ; Base Sequence ; Cloning, Molecular ; Enterovirus ; classification ; genetics ; isolation & purification ; Feces ; virology ; Genome, Viral ; genetics ; Humans ; RNA, Viral ; genetics ; Sequence Analysis, DNA

OBJECTIVETo investigate the clinical implications of relationship between myeloperoxidase and acute coronary syndromes (ACS).

METHODS176 consecutive patients who underwent coronary angiography for coronary atherosclerosis were divided into four groups according to the quartile of MPO Level. The characters and the relationship between MPO and the elements were studied in every group.

RESULTS(1) ACS rate (36.2%) in the fourth quartile group of MPO level was 6 times higher than that (5.2%) in the first quartile group of MPO level, P < 0.01. (2) Gensini score (65.6 +/- 30.3) in the fourth quartile group of MPO level was significantly higher than that (17.3 +/- 10.2) in the first quartile group (P < 0.01). WBC [(7.7 +/- 1.6) x 10(9)/L] in the fourth quartile group was also significantly higher than that [(6.6 +/- 1.8) x 10(9)/L] in the first quartile group, P < 0.05. (3) When TnI < or = 0.05 ng/ml, MPO level had a positive correlation with Gensini score (r = 0.321, P = 0.002) and WBC (r = 0.230, P = 0.025). (4) Kaplan-meier event rate curve showed that there was a significant difference of the terminus incident (death, no causing death AMI, vessel reestablish and incidence rate of CABG add up) between the groups > or = 62.9 AUU/L and < 62.9 AUU/L of MPO serum level at 6-month follow-up visit (chi(2) = 13.5, P = 0.01).

CONCLUSIONActivity level of MPO in human serum seems a good biomarker for diagnosing and predicting ACS, which may be especially helpful in predicting the risk of myocardial infarction in patients with acute chest pain during 6-month follow up.

Acute Coronary Syndrome ; diagnostic imaging ; enzymology ; physiopathology ; Adult ; Angina, Unstable ; diagnostic imaging ; enzymology ; Coronary Angiography ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; enzymology ; Myocardial Ischemia ; diagnostic imaging ; enzymology ; Peroxidase ; blood ; Troponin I ; metabolism

OBJECTIVETo investigate the effects of benzo[a]pyrene (B[a]P) exposure on the behaviors and hippocampal oxidative stress and ATPase in rats and the molecular mechanism of neurobehavioral toxicity of B[a]P.

METHODSA total of 120 male SD rats (21 days old) were randomly and equally assigned to five groups: blank control group, vegetable oil (solvent control) group, and 2.5, 5, and 10 mg/kg B[a]P exposure groups. The rats in B[a]P exposure groups were injected intraperitoneally with B[a]P once a day for 4 consecutive weeks. Then, Morris water maze and shuttle box were used to evaluate the learning and memory abilities of rats; colorimetric assay was used to measure the activities of superoxide dismutase (SOD), Na(+)/K(+)-ATPase, and Ca(2+)/Mg(2+)-ATPase and the content of malonaldehyde (MDA) in the hippocampus; the concentration of Ca(2+) in the hippocampus was measured by fluorescent labeling.

RESULTSCompared with the blank control group and solvent control group, the B[a]P exposure groups exhibited significant increases in escape latency, active avoidance response latency, and passive avoidance response latency and significant decreases in number of platform crossings and active avoidance response frequency in the last test (P < 0.05 for all comparisons), with a dose-effect relationship. In addition, the B[a]P exposure groups had significantly lower activities of SOD, Na(+)/K(+)-AT-Pase, and Ca(2+)/Mg(2+)-ATPase and significantly higher MDA level and Ca(2+) concentration than the blank control group and solvent control group (P < 0.05 for all comparisons), with a dose-effect relationship.

CONCLUSIONThe neurobehavioral toxicity of B[a]P may be related to increased oxidative stress and decreased activities of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase in the hippocampus of rats.

Animals ; Benzo(a)pyrene ; toxicity ; Ca(2+) Mg(2+)-ATPase ; metabolism ; Hippocampus ; drug effects ; metabolism ; Male ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Superoxide Dismutase ; metabolism

Acute intermittent porphyria (AIP) is a metabolic disease caused by hepatic deficiency of hydroxymethylbilane synthase. Its clinical manifestations include acute abdominal pain,neuropsychological abnormalities,and red urine. Due to its low incidence and varied clinical symptoms,the rates of misdiagnosis and mistreatment were particularly high. Biochemical testing and gene detection contribute to diagnosis. Management strategies include intravenous administration of human haemin,carbohydrate loading and symptomatic treatment.