Objective To explore the mechanism of the microglia inflammatory response through observing the changes of interleukin-1 receptor associated kinase-4(IRAK-4) expression in murine N9 microglia cells under hypoxia.Methods N9 cells were exposed to 3%O2,5%CO2,92%N2 for 1,3,6,12 and 24 h respectively.The IRAK-4 protein level was detected by Western blotting and the celluar change was observed by laser scanning confocal microscope(LSCM).The TNF-? level was measured by ELISA.Results After hypoxia,the expression of IRAK-4 protein was increased in a time-dependent manner.The elevation began at 1 h after hypoxia,increased significantly at 3 h(P0.05).The fluorescence intensity of IRAK-4 also increased with the extension of anoxic time.The TNF-? level change were similar.There were significant positive correlations between the expression of IRAK-4 and TNF-?(P

Aspirin ; administration & dosage ; therapeutic use ; Blood Cell Count ; Blood Platelets ; drug effects ; physiology ; C-Reactive Protein ; analysis ; Child, Preschool ; Diagnosis, Differential ; Female ; Humans ; Hydroxyurea ; administration & dosage ; therapeutic use ; Interferons ; administration & dosage ; therapeutic use ; Platelet Count ; Thrombocythemia, Essential ; blood ; diagnosis ; therapy

This article summarizes the progress of hematology in the recent tens years to show that experimental hematology used to pick up the 'hints' from clinical problems as the renewal of research directions and targets in experimental studies continuously. As the feedback, the results from lab investigations inserted into clinical practice and eventually made a quick modernization of hematology, which was actually a good model for the "translational research". The past few decades have witnessed tremendous advances in our understanding of normal hematopoiesis where genes dictate, epigenetics regulate, transcription factors mediate, and stem cells self-renew and differentiate. Dissection of disease pathogenesis not only elucidates molecular basis of disorders including hemoglobinopathy, aplastic anemia, hemophilia, hematopoietic malignancies such as leukemia and myeloproliferative disorders, but also provides therapeutic targets for drug development. Introduction of targeted therapies and combinatory targeting therapies greatly benefits hundreds of thousands of patients, and even turns acute promyelocytic leukemia from highly fatal to highly curable. In the 21st century the experimental hematology is entering the era of genomics and system biomedicine, and the pace of progress extrapolates to a prediction of hematologic neoplasms control in this century.
Animals ; Clinical Laboratory Techniques ; trends ; Hematologic Diseases ; genetics ; metabolism ; physiopathology ; Hematologic Neoplasms ; genetics ; metabolism ; physiopathology ; Hematology ; trends ; Humans

Objective To investigate the psychological condition of the rural residents with HIV/AIDS.Methods Totally 192 subjects with HIV/AIDS residing in countryside of Henan Province(China)were investigated with questionaire and Symptom Check list 90(SCL-90).Results SCL-90 total score,the number of positive items and the score of each factor for the 192 subjects with HIV/AIDS were higher than those of Chinese normal(P

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.

Objective To investigate the roles and significances of MMP-2 and MMP-9 in diffuse proliferative lupus nephritis by repeated renal biopsy.Methods Seventeen patients diagnosed by renal biopsy as WHO typeⅣlupus nephritis were analyzed by immunohistochemistry staining for MMP-2 and MMP-9. Double staining for MMP-2 and MT1-MMP,MMP-9 and CD68 were also performed.Patients had repeated renal biopsy after followed up for 2.5 years.The relationship between expressions of gelatinases and pathological activity index and clinical data were studied.Results MMP-2 immunoreactivity was detected in normal controls and was increased in diffuse proliferative lupus nephritis.MMP-9 staining,which was almost negative in normal giomeruli,was increased much more significantly in diffuse proliferative lupus nephritis. The immunoreactivity of MMP-2 and MMP-9 was positive in MT1-MMP staining and CD68-positive macrophages, respectively.The expression of MMP-2 and MMP-9 was reduced by 70% and 62% in 10 patients whose clinical condition was partially alleviated,while the expressions in 7 patients whose clinical condition was not alleviated,were only reduced by 27% and 32%.The staining for MMP-2 and MMP-9 were correlated with activity index of lupus nephritis and proteinuria.Conclusion Up-regulation of gelatinases expression in diffuse proliferate lupus nephritis is correlated to activity index of the disease.

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 Our previous study demonstrated that the aptamer S58 specifically targeted transforming growth factor-β receptor Ⅱ (TβRⅡ) and inhibited the transdifferentiation of human Tenon capsule fibroblasts (HTFs) mediated by transforming growth factor-β (TGF-β).Chitosan-nanoparticles (CS-NP) are good drug carriers,but the efficacy and safety of CS-NP/aptamer complexes deserve attention.Objective The aim of this study was to synthesize a novel CS-NP/aptamer complex called CS (S58)-NP and investigate its properties and applicability.Methods Human Tenon capsule tissue was obtained from patients during strabismus surgery,and HTFs were cultured and passaged using the explant culture method.The fourth to tenth generations of cells were used in the experiment.Different concentrations of CS-NP were used to prepare the CS(S58)-NP by the ionic cross-linking method with a surface charge rate (N/P) for S58 of 10,20,30 or 40.The particle size and Zeta potential were measured by the Zeta analyzer.The shape and distribution of CS (S58)-NP particles were examined under the scanning electron microscope.The binding of CS-NP with S58 and resistance of CS (S58)-NP to DNase Ⅰ were examined by agarose gel eletrophoresis.The release rate of S58 from CS (S58)-NP in PBS was quantitatively analyzed by a ultraviolet spectrophotometer.The cytotoxicity of CS(S58)-NP to HTFs was evaluated by detecting the production of lactate dehydrogenase (LDH).Results The Zeta analyzer showed that the particle size of CS (S58)-NP was 130-270 nm and its electric potential ranged from + 16 to +28 mV.The CS (S58)-NP particles appeared spherical with an even distribution under the scanning electron microscope.The mean encapsulation efficiency of CS(S58)-NP was 88.9％,89.3％,91.7％ or 90.5％,respectively,when the N/P was 10,20,30 or 40.After being encapsuled by CS-NP,S58 could resist the degradation from DNase I.Its total releasing level in PBS increased with the lapse of time,with a maximum releasing speed at 24 to 36 hours.The total releasing level reached 100％ at 96 hours.With increaseing concentrations of CS(S58)-NP,the relative releasing level of LDH in HTFs suspension gradually elevated with a significant difference among the groups (F =588.018,P =0.000),with the highest released LDH level at 50 nmol/L of CS(S58)-NP (12.853％ ±0.375％).Conclusions CS-NP provides a protective and slow-releasing effect on the S58 aptamer.CS (S58)-NP shows a good biocompatibility with HTFs with a low cytotoxicity at a concentration of ＜50 nmol/L.CS(S58)-NP could be used to inhibit TGF-β induced transdifferentiation of HTFs in the future.

Objective To accurately judge the tumor-feeding artery is the most important basis for a successful treatment of hepatocellular carcinoma (HCC) with super-selective hepatic arterial chemoembo lization therapy. This study aims to assess the clinical value of cone-beam CT hepatic arteriography (CBCT-HA) in detecting tumor-feeding arteries during the performance of conventional transarterial chemoembo lization (TACE), and to compare the diagnostic effects between CBCT-HA and non-selective hepatic DSA. Methods Twenty-three consecutive patients with inoperable HCC were enrolled in this study. TACE was carried out in all patients. During the performance of TACE, the DSA-HA, CBCT-HA, Lipiodol-TACE and Lipiodol-CBCT were performed separately. The imaging materials, including DSA-HA and CBCT-HA, were analyzed by two experienced interventional physicians together to judge the tumor-feeding arteries. Statistic analysis was conducted by using chi square test. Results Tumor stain and lipiodol accumulation were regarded as the “gold standard” of the presence of tumor-feeding artery, based on which the tumor-feeding artery was confirmed in 75 lesions. DSA-HA demonstrated positive tumor-feeding artery in 40 lesions, among which true-positive tumor-feeding artery was seen in 32 and false-positive one in 8. CBCT-HA showed positive tumor-feeding artery in 72 lesions, which included true-positive tumor-feeding artery in 68 and false-positive one in 4. The sensitivity of CBCT-HA in judging tumor-feeding artery was 90.7% (68/75), which was much higher than that of DSA-HA (42.6%, 32/75), the difference was statistically significant(P<0.001). The positive predictive value of CBCT-HA in detecting tumor-feeding artery was also higher than that of DSA-HA (94.4% vs. 80.0%; P=0.040). Conclusion Cone-beam CT hepatic arteriography is obviously superior to DSA hepatic arteriography in identifying tumor-feeding arteries, which is very helpful in guiding super-selective TACE for HCC.

Objective To investigate the characteristics of liver function recovery in steatotic liver graft transplantations.Method From August 1st 2013 to July 20th 2014,a prospective clinical cohort study of liver transplantations was performed in Tianjin First Central Hospital.Multiple linear regression analyses were made for related factors with the degree of donor liver steatosis and the average total bilirubin (TBil) levels on the post-operative day 6 to 8,week 4,and month 3 and 6,respectively.Result Of 82 cases used for analysis,there were 28 cases of mild steatotic grafts and 54 cases of non steatotic grafts.The multiple linear regression analysis revealed the average TBil level on the post-operative day 6 to 8 was the only one index related with the degree of graft steatosis.By the same means,recipient age,the aspartate aminotransferase (AST) level on the post-operative day 1,the average AST level on the post-operative day 2 to 3,and the degree of graft steatosis were associated with the average TBil level on the post-operative day 6 to 8.The AST level on the postoperative day 1,the average AST level on the post-operative day 2 to 3,and the degree of graft steatosis were associated with the average TBil level on the post-operative week 4.But only the AST level on the post-operative day 1 and the average AST level on the post-operative day 2 to 3 were associated with the average TBil level on the 3th and the 6th month post-operation.Conclusion Mild steatotic liver graft can result in increased TBIL level within perioperative period,but the graft function is not affected by it.The average AST level on the post-operative day 2 to 3 can effectively predict the prognosis of the graft.Objective Methods Results Conclusion