Objective To predict the binding sites of transforming growth factor-βreceptor Ⅱ (TβRⅡ ) ectodomain and the aptamer S58 specifically targeted TβRⅡ ,and to confirm the structure stability of the aptamer S 58 in vitro .Methods We created three-dimensional structure by utilizing ssDNA aptamer sequences ,the crystal structure of the TβRⅡ was searched by protein data bank database .According to the results of the molecular docking experiments on aptamer S 58 and TβRⅡ ectodomain ,we sheared the aptamer sequences ,then verified its affinity respectively by biosensor technology and Western blot .Results Binding sites of aptamers S58 and TRβⅡ ectodomain included site Ⅰ(T4 ,T5 ,G6 ,C7) ,site Ⅱ(G13 ,A14 ,T15 ,C16 ,G17 ,C18 ) ,site Ⅲ (T31 ,G32 , T33 ,C34) and site Ⅳ(G40 ,A41 ,T42 ,T43 ,T44 ,G45 ,G46) .We validated the high affinity between aptamer S58 and TRβⅡ ectodo-main .The expression of α-smooth muscle actin(α-SMA) protein in the human tenon′s capsule fibroblasts was descended obviously after the experiment of the aptamer S58 in comparing with the control of DMEM (P< 0 .05) .But the new ssDNA by shear the aptamer ssDNA S58 according to the results were poor than aptamers S58 .Conclusion The aptamer S58 targeted TβRⅡ was high-ly specific with a certain stability ,any changing of structure will reduce the affinity of TβRⅡ .Computer-aided molecular docking technology has become an important means of an exploratory intermolecular interaction ,and can provides a good theoretical basis on medical research .

0.05). After dividing the patients into early-onset and late-onset subgroups, there were significant differences of DRD4 genotype and allele frequency between early-onset patients and controls (P0.05). Conclusion The results suggested that the polymorphism of DRD4 receptor gene may be associated with early-onset OCD. The 3/4 genetype may be the risk factor of early-onset OCD. Early-onset and late-onset OCD may have different etiology.

OBJECTIVETo observe the impact of tonifying Qi traditional Chinese medicines contained in Yiqi Qingwen Jiedu mixture on mRNA expression of lung inflammatory cytokines and pulmonary pathological injury of mice infected by influenza virus, in order to discuss the mechanism of tonifying Qi traditional Chinese medicines against pulmonary immune inflammatory injury of infected mice.

METHODIn different time phases after mice were infected with influenza virus FM1, the RT-PCR method was adopted to observe the impact of tonifying Qi traditional Chinese medicines contained in Yiqi Qingwen Jiedu mixture on five inflammatory cytokines TNF-α, IL-1, IL-6, IL-10 and IFN-γ, and the changes in pulmonary pathological injury of mice with viral pneumonia after intervention with tonifying qi traditional Chinese medicines.

RESULT(1) Tonifying Qi traditional Chinese medicines significantly reduced the mRNA expression of TNF-α at 1-5 d and IL-1 mRNA expression at 7 d, may increase IL-1 mRNA expression in mouse lung at 3 d, significantly reduced IL-6 mRNA expression in mouse lung and increased IL-10 mRNA expression at 3-7 d, and significantly increased IFN-γ mRNA expression at 1 d. (2) Tonifying Qi traditional Chinese medicines could significantly inhibited and repaired pulmonary immune inflammatory injury of mice infected by FM1, which was most remarkable at 3-7 d after the infection with influenza virus FM1.

CONCLUSIONTonifying Qi traditional Chinese medicines contained in Yiqi Qingwen Jiedu mixture could resist pulmonary immune inflammatory injury and repair inflammatory injury by regulating the mRNA expression of imbalance inflammatory cytokines of organisms infected with influenza virus.

Animals ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Influenza A virus ; drug effects ; immunology ; Influenza, Human ; drug therapy ; genetics ; immunology ; Interferon-gamma ; genetics ; immunology ; Interleukin-1 ; genetics ; immunology ; Interleukin-10 ; genetics ; immunology ; Interleukin-6 ; genetics ; immunology ; Lung ; immunology ; virology ; Male ; Mice ; Mice, Inbred BALB C ; Tumor Necrosis Factor-alpha ; genetics ; immunology

OBJECTIVETo study the humoral immunity reconstitution and its relationship with infection in patients with multiple myeloma (MM) after undergoing autologous hematopoietic stem cell transplantation (auto-HSCT).

METHODSForty-two MM patients undergoing auto-HSCT were included in this study. Peripheral blood were obtained for immunoglobulin detection, including IgG, IgA and IgM before transplantation and 1, 3, 6, 12, 18 and 24 months after transplantation. The time, type, pathogen of infection between 1 and 24 month after transplantation were analyzed.

RESULTSThe level of IgA at 6 month [(0.75±0.59) g/L] after auto-HSCT was lower than that of pre-auto-HSCT [(1.04±0.70) g/L], and reached the level of pre-auto-HSCT at 9 months [(0.99±0.52) g/L] after auto-HSCT. The level of IgM reached the level of pre-auto-HSCT [(0.45±0.26) g/L] at 3 months after auto-ASCT [(0.50±0.26) g/L]. The level of IgG reached the level of pre-auto-HSCT [(9.80±2.98) g/L] at 1 month after auto-HSCT [(11.09±2.69) g/L], and higher than that of pre-auto-HSCT at 9 months after auto-HSCT [(12.07±3.57) g/L]. The level of IgG with IgG-type MM was higher than that of patients with light-chain type and IgD-type MM at 6, 9 and 12 months after auto-HSCT. The IgA level of patients who obtained complete remission (CR) is much higher than that of patients who obtained nCR in IgG-type patients. The incidence of infection in 6 month after auto-HSCT was higher than that of (6-12) month and >12 month after auto-HSCT. The incidence of infection was strongly negative correlated with IgA (r =-0.943, P=0.005) and IgG (r=-0.943, P=0.005) level. The frequency of viral infection was also negatively correlated with IgA and IgG.

CONCLUSIONThe reconstitution time of IgG, IgA and IgM was different in MM patients after auto-HSCT. IgG recovered first, then IgM, and IgM the last. The incidence of infection was negatively correlated with IgA and IgG. With the recovery of IgG and IgA, the incidence of infection was decreased accordingly.

Adult ; Aged ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunity, Humoral ; Male ; Middle Aged ; Multiple Myeloma ; immunology ; therapy ; Transplantation, Autologous ; Virus Diseases ; immunology

OBJECTIVETo investigate the time course of nuclear factor-kappaB (NF-kappaB) activation in the process of stress ulcer formation.

METHODSModel of stress ulcer was reproduced by subjecting male Sprague-Dawley rats to water-immersion restraint (WIR) stress. At indicated time after the beginning of WIR stress, animals were sacrificed and cytoplasmic and nuclear protein and total RNA were prepared from gastric corpus mucosal tissues. DNA-binding activity of NF-KB was assessed as an index of NF-kappaB activation with electrophoretic mobility shift assay. Degradation of IkappaBalpha and IkappaBbeta, the inhibitory proteins of NF-kappaB, was analyzed by Western blot analysis. Expression of NF-kappaB dependent genes including tumor necrosis factor-alpha (TNF-alpha) , interleukin-1beta (IL-1beta), cytokine-inducible neutrophil chemoattractant-1 ( CINC-1), intercellular adhesion molecule-1 (ICAM-1), and inducible nitric oxide synthase (iNOS) was detected with Northern blot analysis.

RESULTSWIR stress induced a rapid biphasic activation of gastric mucosal NF-kappaB within 15 min of the beginning of stress, peaking at 45 min and 360 min. Compared with baseline, NF-kappaB activation by stress was increased (10.6 +/- 1.3) and (8.9 +/- 1.2) fold at 45 min and 360 min, respectively (P < 0.01). Antibody supershift assays revealed that p50/p65 heterodimer was the major active component of mucosal NF-kappaB. Western blot analysis showed that degradation of IkappaBalpha and IkappaBbeta occurred at first and second wave of NF-kappaB activation. Corresponding with the rapid and persistent activation of NF-kappaB, the levels of TNF-alpha, IL-1beta, CINC-1 and ICAM-1 mRNA in gastric mucosa were markedly increased 15 to 30 min after stress, respectively. Up-regulation of iNOS mRNAs was observed 30 to 90 min after stress, and the expression of all of these genes was increased consistently until the end of stress.

CONCLUSIONNF-kappaB activation is an early event and may play an important role in proinflammatory gene over-expression in rat gastric mucosa during WIR stress.

Animals ; Chemokine CXCL1 ; metabolism ; Disease Models, Animal ; Gastric Mucosa ; metabolism ; Gene Expression ; Intercellular Adhesion Molecule-1 ; metabolism ; Interleukin-1beta ; metabolism ; Male ; NF-kappa B ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Stress Disorders, Traumatic ; Tumor Necrosis Factor-alpha ; metabolism ; Ulcer ; etiology ; metabolism

OBJECTIVETo evaluate the therapeutic effect of imatinib on chronic myeloid leukemia (CML) in different phases and analyze the factors that may affect the effects.

METHODSEighty-five patients with CML in chronic phase, 24 in accelerated phase and 19 in blastic phase patients were treated with imitinib. The hematologic response, cytogenetic response, molecular response, overall survival (OS), progression-free survival (PFS) and adverse events were analyzed in these groups.

RESULTSThe rates of complete hematologic response (CHR), complete cytogenetic response (CCyR) and complete molecular response (CMoR) of the patients in chronic phase were 100%, 82.4% and 21.2%, respectively, and the 5-year OS and PFS of these patients were 92.1% and 84.7%. All these rates were significantly higher than those in patients in accelerated and blastic phases (P<0.0001). The CCyR, CMoR, 5-year OS and PFS in the 42 newly diagnosed patients in chronic phase were 92.9%, 26.3%, 100% and 95.2%, respectively, all significantly higher than those in patients with interferon therapy failure (P<0.001). Severe leukocytopenia and thrombocytopenia occurred at greater frequencey in AP and BP patients than in chronic phase patients (P<0.0001). Non-hematologic toxicity was rarer and milder in patients in chronic phase. Multivariate analysis showed that interferon therapy prior to imitinib treatment and prolonged drug cessation were the independent factors that affected the achievement of cytogenetic response and PFS.

CONCLUSIONEarly imitinib therapy can be effective and safe, and should be used as the first line drug for CML.

Antineoplastic Agents ; therapeutic use ; Benzamides ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Leukemia, Myeloid, Chronic-Phase ; drug therapy ; Male ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; Treatment Outcome

OBJECTIVETo investigate the association between single nucleotide polymorphisms (SNPs) in cyclic adenosine monophosphate response element-binding protein(CREB1) gene and major depressive disorder (MDD).

METHODSWe recruited 105 parent-offspring trios of Chinese descent, extracted whole blood genomic DNA, and genotyped the SNPs in rs10932201 and rs6740584 loci. Single-marker transmission disequilibrium test (TDT), pairwise SNP linkage disequilibrium(LD) and haplotype-based TDT were performed.

RESULTSNo significant association with MDD was observed for SNPs rs10932201 and rs6740584 (P=0.1004 and P=0.4986). However, there was strong positive association between the rs10932201-rs6740584 haplotype and MDD (P=0.00003241), and both haplotypes of A-C and A-T were significantly associated with MDD (P=0.020 and P=0.00022).

CONCLUSIONThe rs10932201-rs6740584 haplotype of the CREB1 gene may play an important role in the pathogenesis of MDD.

Cyclic AMP Response Element-Binding Protein ; genetics ; Depressive Disorder, Major ; genetics ; Female ; Genetic Predisposition to Disease ; Haplotypes ; Humans ; Male ; Polymorphism, Single Nucleotide ; genetics

This study was purposed to investigate the relationship between the levels of soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin (OPG) in serum of the patients with multiple myeloma (MM) and multiple myeloma bone disease (MBD). The serum levels of sRANKL, OPG, tartrate-resistant acid phosphatase-5b (TRAP-5b) and C-terminal telopeptide of collagen I (CTP-I) which both are indexes for metabolism of osteoclast (OC) in newly diagnosed MM patients (n=42, experimental group) and healthy persons (n=25, control group) were detected by enzyme-linked immunosorbent assay. The roentgenography was used to determine bone damage in MM patients at the same time. According to these results acquired, the correlation of sRANKL/OPG ratio with levels of TRAP-5b/CTP-I, the incidence and degree of bone destruction were analyzed. The results indicated that the level of sRANKL (median value 9.33 microg/L) increased and level of OPG (median value 4.93 microg/L) decreased and the sRANKL/OPG ratio (2.65) increased significantly in experimental group. Compared with control group, the differences in all the corresponding indicators were statistically significant (p<0.05). The sRANKL/OPG ratio was closely related to levels of TRAP-5b (r=0.512, p<0.05) and CTP-I (r=0.481, p<0.05) in MM patients. After all patients in experimental groups were divided into group with bone destruction (n=29) and without bone destruction (n=13), the sRANKL/OPG ratio in the group with bone destruction was 5.13 and much higher than that in group without bone destruction (1.12) (p<0.05). A close correlation between the sRANKL/OPG ratio and degree of bone destruction (r=0.445, p<0.05) was acquired when all MM patients were divided into three groups according to degree of bone destruction, but no difference between the ratio and clinical classification and International Staging System (ISS) in MM patients was found. It is concluded that the sRANKL/OPG ratio in serum of MM patients is significantly elevated, which may be closely related to increase metabolism of OC along with the incidence and degree of bone destruction. In short, the sRANKL/OPG ratio can be used as a reference index for the diagnosis of MBD.
Adult ; Aged ; Bone Diseases ; blood ; diagnosis ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; blood ; diagnosis ; Osteoprotegerin ; blood ; RANK Ligand ; blood

OBJECTIVETo study the clinical significance of abnormal protein bands (APB) in multiple myeloma (MM) patients treated with bortezomib-based induction regimen and autologous stem cell transplantation (ASCT).

METHODSSixty-eight MM patients submitted to bortezomib-based induction therapy and ASCT from January 2007 to July 2012 were retrospectively studied. Monoclonal protein was detected by immunofixation electrophoresis (IFE).

RESULTSOf all 68 patients, 33 (48.5%) patients had APB. At the first emergence of an APB, two patients with light chain type achieved CR and before transplantation, and thirty-one patients were after transplantation with median time of 104 (ranged 33-404) days. The median duration of APB appearance was 105 (ranged 35-801) days. Patients who developed APB compared with those without APB, had a significantly higher CR plus very good partial response (VGPR) rates (100.0% vs 85.7%%, P=0.017) and CR rates (87.9% vs 62.9%) (P=0.03). There were no significant differences in gender, age, HGB, ALB, β2-microglobulin, M protein type, Durie-Salmon and ISS stages, the case number of first line or second line treatment, induction courses of bortezomib-based regimen, and the mode of ASCT. With a median follow-up of 33.4 (ranged 7.0-71.7) months, patients with APB tended to have a longer overall survival (OS) versus non-APB patients, although no significant difference obtained (P＞0.05). Among APB patients, OS was longer in patients whose appearance of APB occurred ＜6 months after transplantation than those ≥ 6 months, but the significant difference was not obtained yet (P＞0.05).

CONCLUSIONSPatients who developed APB had a significantly better response to bortezomib-based induction regimen followed ASCT. APB emergence has a good prognostic significance.

Adult ; Aged ; Boronic Acids ; therapeutic use ; Bortezomib ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; metabolism ; therapy ; Myeloma Proteins ; metabolism ; Prognosis ; Pyrazines ; therapeutic use ; Retrospective Studies ; Transplantation, Autologous

OBJECTIVETo investigate the changes in the expression of beta-catenin in patients with chronic myeloid leukemia (CML) in different phases, and explore the relationship between beta-catenin and the cytogenetic response to imatinib mesylate.

METHODSBeta-catenin mRNA and protein expressions were detected by RT-PCR and Western blotting in the bone marrow mononuclear cells (BMMNCs) from 99 CML patients. The expressions of BCR-ABL fusion gene at both the mRNA and protein levels were detected by fluorescence in situ hybridization (FISH) in 94 patients before and during the one-year treatment with imatinib mesylate at the interval of 3 months, and the relationship between beta-catenin and cytogenetic response to imatinib mesylate was analyzed.

RESULTSThe expression of beta-catenin increased significantly in patients with blast crisis and accelerated phase (P<0.001), but showed no significant difference between normal subjects and CML patients in the chronic phase (P>0.05). The main cytogenetic remission rate was significantly higher in patients who were consistently negative for beta-catenin than in those consistently positive for beta-catenin or those with a positive transformation (P<0.001).

CONCLUSIONBeta-catenin overexpression in the progression of CML, consistent high level of beta-catenin or a positive transformation may indicate a poor response to imatinib, and early measures should be taken to increase the remission rate.

Adolescent ; Adult ; Benzamides ; therapeutic use ; Blast Crisis ; drug therapy ; genetics ; metabolism ; Case-Control Studies ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; RNA, Messenger ; genetics ; Young Adult ; beta Catenin ; metabolism