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 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.

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 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.

BACKGROUND: This study was undertaken to determine the effect of mesenchymal stem cells (MSCs) engraftment on vascular endothelial cell growth factor (VEGF) in lung tissue, plasma and extravascular lung water at early stage of smoke inhalation injury. METHODS: A rabbit smoke inhalation injury model was established using a home-made smoke inhalation injury generator, and rabbits were divided into two groups randomly: a control group (S group, n=32) and a MSCs treatment group (M group,n=32). 10 ml PBS was injected via the ear marginal vein immediately at injury into the S group. Third generation MSCs with a concentration of 1×107/10 ml PBS were injected via the ear marginal vein immediately at injury into the M group. VEGF in peripheral blood and lung tissue were measured at 0 (baseline), 2, 4 and 6 hours after injection respectively and analyzed. The right lungs of rabbits were taken to measure lung water mass fraction. RESULTS: In the lung tissue, VEGF decreased gradually in the S group (P<0.05) and signifi cantly decreased in the M group (P<0.05), but it increased more signifi cantly than the values at the corresponding time points (P<0.05). In peripheral blood, VEGF increased gradually in the S group (P<0.05) and markedly increased in the M group (P<0.05), but it decreased more signifi cantly than the values at corresponding time points (P<0.05). CONCLUSION: MSCs engraftment to smoke inhalation injury could increase VEGF in lung tissue, decrease VEGF in plasma and reduce extravascular lung water, indicating its protective effect on smoke inhalation injury.

OBJECTIVETo evaluate the efficacy and safety of Chinese herbal medicine combined with systemic chemotherapy and/or regional arterial perfusion for pancreatic cancer with liver metastases (PCLM).

METHODSWe retrospectively selected 292 patients with PCLM who were treated by Chinese herbal medicine combined with systemic chemotherapy and/or regional arterial perfusion at Tianjin Medical University Cancer Hospital from January 2001 to December 2010. All patients were assigned to the Western medicine treatment group (157 cases) and the integrative medicine treatment group (135 cases). Patients in the Western medicine treatment group were treated with gemcitabine (GEM)-based chemotherapy, and partial of them received regional arterial perfusion. Those in the integrative medicine treatment group additionally took Chinese herbs of clearing heat and eliminating mass for at least 4 weeks. The median survival time (MST) , adverse reactions and the incidence of complications were observed.

RESULTSThere was no statistical significance in general data between the two groups (P > 0.05). There was statistical difference in MST between the two groups (4.8 months vs 5.5 months, P < 0.05). No death occurred during chemotherapy or regional arterial perfusion. All toxic or adverse reactions were tolerable.

CONCLUSIONChinese herbal medicine combined with systemic chemotherapy and/or regional arterial perfusion was effective and safe, and it could be optimally selected as palliative therapy for PCLM.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Complementary Therapies ; methods ; Deoxycytidine ; analogs & derivatives ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Pancreatic Neoplasms ; drug therapy ; pathology ; Retrospective Studies