Objective To investigate the cause of high cardiovascular lethality in patients with diabetics mellitus. Methods Sections from autopsied coronary arteries and myocardium of dead patients with non-insulin-dependent diabetics mellitus and 12 dead control subjects were used for histomorphometric studies. Results The coronary atherosclerotic lesion in diabetics patients was not different in severity from those in controls. Nor was there difference in number of myofibers or diameters of myocardic fibers and capillaries.But the capillary density and the ratio of capillary number to myocardic fiber number in diabetics group were significeantly reduced compared with control group(P<0.0 l),and the capillary basement membrane in the former was significantly thicker than in the latter(P<0.01).Conclision The decrease in number of capillaries and the thickening of basement membrane enhance myocardiac vulnerability to further ischemia and hypoxia,which may undelie high lethality of myocardiopathy in diabetic patients.

Objective To explore the role of tissue inhibitor of metalloproteinase-1(TIMP-1) during renal senescence by using human TIMP-1 transgenic mice.Methods Renal histological changes of wild type mice and transgenic mice at the age of 3,12,24 months were observed by periodic acid-schiff(PAS)staining of paraffin sections.The numbers of F4/80 positive cells were detected by immunofluoreseence.The protein expressions of TIMP-1,TIMP-2,matrix metalloproteinase(MMP)-9,MMP-2,intercellular adhesion molecule-1(ICAM-1),transforming growth factor?1(TGF-?1),collagenⅢand collagenⅣwere detected by Western blot.The activities of gelatinases and TIMP-1 were examined by gelatin zymography and reverse zymography respectively.Results Focal renal fibrosis was found in two genotypes with aging.At the age of 24 months,compared with wild type,in kidneys of transgenic type,the expressions and activities of gelatinases were dowregulated (MMP-2:2.08?0.20 vs.3.39?0.43;MMP-9:4.02?0.82 vs.6.72?1.40,all P＜0.05);the expressions of collagenⅢ,collagenⅣ,ICAM-1,and TGF-?1 were upragulated(0.72+0.11 vs.0.57?0.09;0.84?0.13 vs.0.6?0.11,0.72?0.12 vs.0.53?0.07; 0.69?0.12 vs.0.45?0.09,all P＜0.05),and the numbers of F4/80 positive cells were increased (18.8?4.4 vs.12.7?3.6,P＜0.05)with the upregulated expression and activity of TIMP-1(1.10?0.18 vs.0.62?0.09;50.75?7.25 vs.20.64?3.50,P＜0.05).Conclusions TIMP-1 could promote age-related renal fibrosis through enhancing inflammation reaction by ICAM-1 upregulation.

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 study the susceptible factors of atherosclerotic stenosis before the coronary artery myocardial bridges.Methods The data from 88 myocardial bridge cases which received coronary angiography were statistically analyzed.Sixty-seven cages which suffered from atherosclerofic stenesis in proximal of the myocardial bridges were recruited into group A,and the other 21 cases which suffered no atherosclerotic stenosis or from atherosclerotic stenosis in distal of the myocardial bridges were mcmited into group B.Difference of the age,gender,length of myocardial bridge,systolic blood pressure (SBP),diastolic blood pressure (DBP),pulse pressure (PP),the oppression degree of myocardial bridge (Nobel classification),fasting plasma glucose (FPG),and blood fat,and so on,in two groups,were observed and statistically analyzed.Results The difference of the Nobel classification,SBP and PP in two groups showed a statistical significance (P＜0.05).While the difference of the age,gender,length of myocardial bridge,DBP,FPG,total cholesterol,low-density hpoprotein in two groups showed no statistical significance (P＞0.05).A further regression analysis suggested that Nobel classification and PP had a correlation with the comphcation of stonosis before the myocardial bridge (r=3.0569,0.9740,P＜0.05).Conclusions High blood pressure cases are liable to suffer from myocardial bridge.Myocardial bridges themselves trend to promote or accelerate the atherosclerotic stenosis of the coronary arteries before.them.The oppression degree of myocardial bridge and PP has a correlation with the complication of stenosis before the myocardial bridge,while has no correlations with age,gender,bloodfat,SBP,DBP,FPG,length of myocardial bridge,and so on.

ObjectiveTo investigate prognostic factors in Stage Ⅲ non-small cell lung cancer (NSCLC)treated with definitive radiation therapy (RT) with PET-CT-based radiotherapy planning. MethodsFifty nine patients with Stage Ⅲ NSCLC treated with radiation therapy of 60 Gy or more were enrolled into this study.The impact of prognostic factors on survival was evaluated by univariate and multivariate analyses. Results The following-up rate was 98％.Nineteen patients completed 2 years' followed-up. The overall l-year and 2-year survival rate was 66％ and 37％, respectively, with a median survival time of 17 months. At a univariate analysis, cigarette smoking status, T stage, radiation dose, the standardized uptake value, the gross tumor volume and clinical stage were significant prognostic factors ( x2 =7.46,7. 52,8.37,4. 97,5.82,4. 37, P =0. 006,0. 006,0. 004,0. 026,0. 016,0. 037, respectively ).At multivariate analyses, cigarette smoking status, radiation dose, gross tumor volume and clinical stage were significant prognostic factors ( x2 =6. 20, 9. 69, 6. 39, 10. 09, P =0. 013,0. 002, 0. 011,0. 001,respectively). Conclusions Cigarette smoking status, radiation dose, gross tumor volume and clinical stage are significant prognostic factors on survival in patients with Stage Ⅲ NSCLC treated with RT based on PET-CT radiotherapy planning.

OBJECTIVETo observe the clinical effects of two different circumcision procedures with the Shang Ring and compare their advantages and disadvantages.

METHODSA total of 527 adult males with phimosis or redundant prepuce underwent Shang Ring circumcision by conventional outward replacement (n = 254) and inward placement (n = 273), respectively. We observed the in-ring nocturnal pain, complications, ring-removal pain, degree of edema, recovery time, and patients' satisfaction after surgery, and compared them between the two groups.

RESULTSCompared with the conventional outward placement (5.9%) of the Shang Ring, the inward placement method showed the advantages of mild in-ring nocturnal pain, a low complication rate, significantly reduced ring-removal pain, and mild edema, but exhibited longer healing time.

CONCLUSIONIn Shang Ring circumcision for phimosis and redundant prepuce in adult males, each of the outward and inward placement methods has advantages and disadvantages of its own, but the latter is more advantageous and feasible.

Adult ; Circumcision, Male ; adverse effects ; instrumentation ; Edema ; etiology ; Foreskin ; abnormalities ; surgery ; Humans ; Male ; Pain, Postoperative ; Patient Satisfaction ; Penile Diseases ; etiology ; Penis ; abnormalities ; surgery ; Phimosis ; surgery ; Prostheses and Implants ; Wound Healing

Objective To explore the associations between microsatellites in gonadal receptor genes and dysfunctional attitudes in adolescent with major depressive disorder(MDD).Methods Polymerase chain reaction(PCR),capillary electrophoresis and genetic scanning were performed in testing the length of microsatellites in first-onset adolescent depressive patients.Dysfunctional attitudes scale(DAS) was used in rating the dysfunctional cognition of adolescent depressive sample.These results were tested by correlative analysis and comparison analysis.Results 1.There existed significantly negative correlation between microsatellite′s length in estrogen receptor ?(ER?) gene and total score of DAS in female adolescent patients with first-onset depressive disorder.2.DAS′ total score of shorter alleles′ group was significantly higher than that of longer alleles′ group on female′ estrogen receptor ?(ER?) Gene.Conclusion The microsatellite′s length of ER? and ER? gene may have associations with dysfunctional attitudes of female adolescent with MDD.

“Mechanical memory” approach was commonly used in the knowledge learning of traditional Chinese medicine, which makes students often feel that the knowledge is too abstract, and this method is thus ineffective. “Qihuang the way” using Unity 3D game development platform inte-grates the elements of medical knowledge of the Chinese medical history, and combines TCM theoretical knowledge learning with serious games , which can help invoke students' enthusiasm and improve learning efficiency in an entertaining way.

Trypanosoma is a human parasite severely affecting poor tropical areas.However,current frontline drugs for Trypanosoma treatment have severe side-effects with decreased effectiveness.Based on the fact that aminoacyl-tRNA synthetase is a bonafide drug target for several microorganisms,including bacteria and fungi,it is plausible that it may also be effective target of Trypanosoma.The Trypanosoma brucei leucyl-tRNA synthetase(tbLeuRS)was cloned,expressed and purified to develop an in vitro enzymatic assay system.The assay conditions were further optimized for the effective screening of tbLeuRS inhibitors thus establishing an anti-Trypanosoma drug screening system targeting tbLeuRS.The results indicated that this system can be employed for the effective screening of anti-Trypanosoma drugs with satisfactory specificity.In addition,this system can also be used for compound optimization,as well as IC50 testing.Using this system a series of compounds are identified that are effective Trypanosoma inhibitors without toxicity to human cells.Therefore,targeting tbLeuRS may represent a new venue for the development of anti-Trypanosoma drugs.

cDNA for Insulin-like growth factor binding protein 3 was cloned and constructed a prokaryotic expression vector--pET-DsBA-IGFBP3. The construct was transformed into E. coli BL21 (DE3)plysS. The induced fusion protein (D-IGFBP3) was expressed successfully in soluble form. We obtained D-IGFBP3 the purify of which is over 95% after purification by His affinity chromatography. The product was identified by Western-blot. The cell assay showed that the obtained fusion protein can inhibit the growth of MCF-7 and bind with IGF-I in vitro.
Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chromatography, Affinity ; Dose-Response Relationship, Drug ; Electrophoresis, Polyacrylamide Gel ; Enzyme-Linked Immunosorbent Assay ; Escherichia coli ; genetics ; Gene Expression ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; genetics ; metabolism ; pharmacology ; Insulin-Like Growth Factor I ; metabolism ; Protein Binding ; Recombinant Proteins ; isolation & purification ; metabolism ; pharmacology ; Solubility