Objective To evaluate the efficacy,safety and impact of recombinant human cytotoxic T lymphocyte-associated antigen (CTLA)-4 fusion proteins (rhCTLA-4Ig) on serum human tumor necrosis factor (TNF)-α and CX3CL1 in active rheumatoid arthritis (RA) patients.Methods Forty-four RA patients were treated with rhCTLA-4Ig and placebo.Clinical response was assessed by American College of Rheumatology (ACR) criteria and disease activity score in 28 joints (DAS28).The levels of serum TNF-α and CX3CL1 were determined in 44 RA patients and 20 healthy controls by enzyme-linked immunosorbent assay (ELISA).Comparisons between groups were performed by t-test or x2 test.Results At week 12,ACR20,ACR50and ACR70 responses in RA patients with rhCTLA-4Ig were achieved by 95％(20/21 ),76％( 16/21 )and 19％(4/21) respectively,but no patient with placebo achieved ACR20,ACRS0 and ACR70 responses.There were significantly statistical differences in ACR20 and ACR50 responses (x2=39.17,26.69,P＜0.01 ).At week 12,the mean DAS28 in the rhCTLA4Ig group was 3.1±1.3 versus 6.2±1.1 at baseline (P＜0.01).Similarly,health assessment questionnaire (HAQ) improved significantly,declining from 1.4±0.5 at baseline to 0.4±0.5 at week 12 (P＜0.01).However,the mean DAS28 in the placebo group was 5.8±1.2 versus 6.0±0.7 at baseline (P＞0.05),HAQ declined from 1.6±0.4 to 1.6±0.6 (P＞0.05).In addition,there were higher levels of TNF-α and CX3CL1 in the active RA patients than those of the healthy controls (P＜0.01).After 12 weeks therapy,Serum TNF-α and CX3CL1 levels in the rhCTLA-4Ig group decreased significantly (P＜0.01).There weren't decline in the placebo group (P＞0.05).Conclusion This study has shown that rhCTLA-4Ig is very effective in reducing disease activity,improving function during the 12 weeks treatment.rhCTLA-4Ig therapy for 12 weeks can lead to significant decrease of serum TNF-α and CX3CL1.

Objective To analyze the risk of embolization of brain AVMs,study the angioarchitectural factors affecting the difference of embolization level,and to establish the angioarchitecture grading system for embolization of brain AVMs.Methods The clinical data,angioarchitectural features, embolism complication and embolism level were retrospectively analyzed.Multivariate statistical analysis was performed to determine if any of the variables was predictive of a poor outcome of embolization(death or permanent neurological deficit),and if any of the variables was predictive of the percentage obliteration achieved by embolization.Based on the above results,we established the angioarchitecture grading system.Results Endovascular procedures for embolization were performed 324 times in 189 patients during an 11-year period.Embolization was performed using N-butyl cyanoacrylate.In those patients,3(1.6%) died and 5(2.6%)had a permanent neurological deficit as a result of the embolization.The AVMs were given a score from 0 to 5 based on the size,number of the first grade feeding artery,and number of the second grade feeding artery.The assigned scores were as follows:nidus size(AVF=0,

OBJECTIVETo explore the effect of static magnetic field (SMF) on the differentiation and proliferation of rat embryonic midbrain neurons cells.

METHODSThe micromass culture of rat embryonic midbrain neurons cell was applied to study the effect of varieties of SMF (1.0, 10.0, 50.0, 100.0, 200.0 mT) and FACS.

RESULTSSMF inhibited the differentiation of the cell without affecting cell proliferation. The concentration of 50% inhibition of cell differentiation (ICD(50)) was 25 mT. The concentration of 50% inhibition of cell differentiation (IVD(50)) was 45 mT.

CONCLUSIONSThe inhibition of SMF on embryonic midbrain neurons cells may be associated with impact of protein syntheses, and lipid peroxidation.

Animals ; Cell Differentiation ; radiation effects ; Cell Division ; radiation effects ; Cells, Cultured ; Electromagnetic Fields ; adverse effects ; Embryo, Mammalian ; Female ; Lipid Peroxidation ; radiation effects ; Mesencephalon ; cytology ; radiation effects ; Neurons ; cytology ; radiation effects ; Protein Biosynthesis ; radiation effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the effect of extracts of Ginkgo biloba leaf (EGb), a catalyzer of central nervous system, on learning-memory ability and possible mechanism in rats with kindling-induced epilepsy.

METHODSForty postnatal day 21 (P21) and 40 postnatal day 35 (P35) Sprague-Dawley (SD) rats were randomly respectively assigned to five groups: normal sodium (NS) control, kindling epilepsy model, high, middle and low dosage of EGb-treated kindling epilepsy. The kindling epilepsy model was established by an intraperitoneal injection of pentetrazole (PTZ). The learning-memory ability and NMDA receptor 1 (NMDAR1) expression in the hippocampus were measured by Y-maze test and immunohistochemistry assay respectively.

RESULTSThe stimulation times for reaching to academic standard in the Y-maze test in the two ages PTZ kindling groups was significantly more than that in the corresponding NS control groups (P<0.01). After EGb treatment the achievement of the Y-maze test in the three treatment groups was significantly improved in a dose-dependent manner, the higher the dosage, the better the achievement (P<0.01). Immunohistochemistry assay showed that the expression of NMDAR1 in the two ages PTZ kindling groups was significantly higher than that in the corresponding NS control groups (P<0.01). Compared with the corresponding untreated kindling model groups, the expression of NMDAR1 in the two ages EGb treatment groups was significantly reduced in a dose-dependent manner (P<0.01).

CONCLUSIONSEGb can improve learning-memory ability in epileptic rats at different developmental phases in a dose-dependent manner, possibly through a reduction of NMDAR1 expression in the hippocampus.

Animals ; Epilepsy ; drug therapy ; psychology ; Female ; Ginkgo biloba ; Hippocampus ; chemistry ; Immunohistochemistry ; Kindling, Neurologic ; Learning ; drug effects ; Male ; Memory ; drug effects ; Plant Extracts ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; analysis

Objective To investigate the causes,consequences and management of injuries to the draining veins after embolization of brain arteriovenous malformations(BAVMs)with ?-n-butyl cyanoacrylate (NBCA).Methods The angiographic imaging data of 189 BAVMs patients who underwent NBCA embolization were studied retrospectively.The status of the draining veins before and after NBCA embolization was observed and compared.The intracerebral hemorrhage(ICH)complications and their relation to their angiographic features were analyzed.Results Twenty-three patients out of 189 patients showed injuries to the draining venous system,including 10 low-grade injury,6 moderate injury,and 7 high- grade injury.Six patients suffered from ICH after embolization,of whom 4 patients were due to injuries of the draining veins(2 moderate and 2 high-grade).In the 3 months follow-up evaluation of 4 patients with ICH, one died,one was in vegetative state,and the other two patients suffered from residual severe or minor (1 patient for each)permanent neurological deficits.Conclusion Our findings suggest that injury of the draining veins is the major cause of ICH and may lead to serious consequences after embolization of BAVMs with NBCA.

OBJECTIVEIn order to understand the epidemiological and virologic characteristics of coronavirus HKU1 infection in hospitalized children with acute respiratory tract infection (ARTI) in Changsha.

METHODS1165 nasopharyngeal aspirates (NPA) specimens were collected from hospitalized children with ARTI between September 2007 and August 2008 in Changsha. Specimens were screened for pol gene of coronavirus HKU1 by polymerase chain reaction. All positive amplification products were confirmed by sequencing and compared with those in GenBank.

RESULTSCoronavirus HKU1 were detected in 12 patients (1.03%) out of the 1165 children. The patients were from 8 days to 3 years. The most common clinical diagnosis was bronchopneumonia(83.33%). Similarity of coronavirus HKU1 with those published in the GenBank at nucleotide levels was 98.18% - 100%.

CONCLUSIONCoronavirus HKU1 may be important pathogens in children with acute lower respiratory tract infection. Coronavirus HKU1 infections are common in children under 3 years old. There is no significant difference in the infectious rate between the boys and the girls. The peak of its prevalence is in spring and winter. A single genetic lineage of Coronavirus HKU1 was revealed in human subjects in Changsha.

Acute Disease ; Child, Hospitalized ; Child, Preschool ; China ; Coronavirus ; classification ; genetics ; isolation & purification ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Phylogeny ; Polymerase Chain Reaction ; Respiratory Tract Infections ; virology

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease of transformed hematopoietic progenitor cells. In order to investigate the role of sphingosine kinase-1 (SphK-1)/sphingosine 1-phosphate (S1P) signal pathway in the expression of CML cells, and to explore whether P210(bcr/abl) involved is activating SphK-1/S1P signal pathwey, the expressions of SphK-1 and S1P receptor mRNA in bcr/abl positive K562 cells and bcr/abl positive primary CML cells were detected by RT-PCR, the imatinib mesylate, the specific inhibitor of P210(bcr/abl) was employed to inhibit the P210(bcr/abl) tyrosine kinases of K562 cells and CML primary cells, and then the intracellular SphK-1 activity was assayed. The results indicated that after being cultured with 2.5 micromol/L imatinib mesylate for 0.5, 2, 6, 24 and 48 hours, the intensions of inhibiting SphK-1 activity were 0.007%, 38.9%, 34.6%, 28.1% and 76.1% resepectively. SphK-1 activity in CML cells also was reduced by 2.5 micromol/L imatinib mesylate (16.8% - 41.9% decrease). It is concluded that the CML cells express SphK-1 and different S1P receptor, and P210(bcr/abl) fusion protein in CML cells can activate SphK-1.
Benzamides ; Fusion Proteins, bcr-abl ; genetics ; metabolism ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; metabolism ; Lysophospholipids ; genetics ; metabolism ; Phosphotransferases (Alcohol Group Acceptor) ; genetics ; metabolism ; Piperazines ; pharmacology ; Pyrimidines ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Signal Transduction ; genetics ; Sphingosine ; analogs & derivatives ; genetics ; metabolism

OBJECTIVETo investigate the prevalence and clinical characterization of HCoV-NL63 (NL63) in children with acute respiratory tract infections (ARTIs) in Lanzhou with other respiratory viruses. The prevalence of HBoV1 in ALRTI was obviously city,China.

METHODFrom November 2006 to October 2009,1169 nasopharyngeal aspirates (NPA) were collected from children under 14 years old with ARTIs. Samples were screened for NL63 using a reverse transcription-polymerase chain reaction (RT-PCR) and sequencing. Demography and clinical information were recorded.

RESULTNL63 was detected in 35 (2.99%) of the 1169 children. The peak of the positive rate were in August, September 2007, July, August 2008 (23.53%,17.65%, 50%, 33.33% separately). There are no NL63 positive samples was detected in December, 2007 to February 2009. 25 (25/35, 71.43%) were co-infected with other respiratory viruses, and human rhinovirus (HRV) were the most common additional respiratory virus. No significant differences of infective rate of NL63 was found between < or = 3 years age group and > 3 years age group. Bronchiolitis and pneumonia were the most frequent diagnoses in NL63 positive patients and the major symptoms were fever and cough in our study. Between the monoinfection group and the coinfection group of NL63-positive patients, no differences were found in symptoms and clinical diagnoses except symptoms of gastrointestinal.

CONCLUSIONHCoV-NL63 is an important pathogen of acute respiratory tract infection in children in Lanzhou city. The peak of HCoV-NL63 infections was in summer. There were annual differences in the prevalence of HCoV-NL63. HCoV-NL63 infections existed a high rate of mixed infection, and mixed infection does not increase the severity of the disease.

Acute Disease ; epidemiology ; Adolescent ; Child ; Child, Preschool ; China ; epidemiology ; Coronavirus NL63, Human ; genetics ; isolation & purification ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Prevalence ; Respiratory Tract Infections ; diagnosis ; epidemiology ; virology

OBJECTIVETo investigate prevalence of Saffold virus (SAFV) in Changsha area of hospitalized children with respiratory tract infection, and to discuss whether this virus is related to respiratory tract infection of children.

METHODS643 nasopharyngeal aspirates samples were collected from hospitalized children with respiratory tract infection of the first affiliated hospital of Hunan nomal university during Nov. 2007 to Oct. 2008. Real-time fluorescent quanti-tative PCR(FQ-PCR) performed to screen the 5'UTR gene. And then analyze clinical data.

RESULTSSAFV were detected in 67 patients (10.42%) out of the 643 children, it was not detected over 5 years of age. The virus were detected in 8 patients (25.81%) out of the 31 children with persistent pneumonia and chronic pneumonia, there was statistically significant.

CONCLUSIONThere existed SAFV infection in hospitalized children with lower respiratory infection in Changsha area; SAFV maybe related to disease onset with lower respiratory tract infection of children.

Adolescent ; Cardiovirus ; genetics ; isolation & purification ; Child ; Child, Preschool ; China ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Polymerase Chain Reaction ; Respiratory Tract Infections ; virology

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease of transformed hematopoietic progenitor cells. It is now clear that the chimeric bcr/abl P210(bcr/abl) fusion protein, which is generated by the reciprocal translocation t (9; 22), inhibits apoptosis and increase proliferation. P210(bcr/abl) plays a central role in the pathophysiology of CML. The purpose of this study was to construct a cell line model that bcr/abl expression can be regulated by Tet-off inducing-expression-system. The full-length b3a2 bcr/abl cDNA was subcloned into the pTRE2hyg expression vector to construct the pT2-P210 plasmid. 293 cells were firstly transfected with Tet-off plasmid and the clone that the Tet-off system can work effectively after transfected with pTRE2hyg-LUC was selected by luciferase activity assay. The pT2-P210 plasmid was then transfected into the selected clone and cells were then selected for hygromycin B and G418 resistance. The results showed that individual subclones expressing bcr/abl after withdrawing doxycycline were 293pT2-P210 cell line. In conclusion, selected 293pT2-P210 cells are cells that bcr/abl expression can be regulated by Tet-off inducing-expression-system. They are suitable thoroughly to study the function of bcr/abl fusion gene and its signal regulation mechanism.
Base Sequence ; Cell Line, Transformed ; cytology ; physiology ; Chromosomes, Human, Pair 22 ; genetics ; Chromosomes, Human, Pair 9 ; genetics ; Fusion Proteins, bcr-abl ; biosynthesis ; genetics ; Gene Expression Regulation, Neoplastic ; Genes, abl ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; metabolism ; pathology ; Models, Genetic ; Molecular Sequence Data ; Proto-Oncogene Proteins c-bcr ; genetics ; Transfection ; Translocation, Genetic ; Tumor Cells, Cultured