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.

The chemical constituents from Euphorbia lunulata was investigated in this paper. Fourteen compounds were isolated and purified by column chromatographies on silica gel and preparative HPLC. Their structures were identified by physiochemical properties and NMR data analysis as lupeol (1), euphol (2), cassipourol(3) , 24-methylenecycloartan-3beta-ol (4), 24-hydroperoxycycloart-25-en-3beta-ol (5), 25-hydroperoxycycloart-23-en-3beta-ol (6), betulin (7), uvaol (8), (23E) -25-methoxycycloart-23-en-3beta-ol (9), (23E) -cycloart-23,25-dien-3beta-ol (10), 24-methylenecycloartan-3beta, 28-diol (11), salicinolide (12), 2alpha, 3beta, 5alpha, 9alpha, 15beta-pentaacetoxy-11,12-epoxy-7beta, 8alpha-diisobutyryloxyjatropha-6 (17) -en-14-one (13) and 3beta, 5alpha, 15beta-triacetoxy-7beta-isobutyryloxy-9alpha-nicotinoyloxyjatropha-6 (17), 11(E)-dien-14-one (14). Among them, compounds 1-11 were isolated from E. lunulata for the first time.
Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Euphorbia ; chemistry ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Spectrometry, Mass, Electrospray Ionization ; Stereoisomerism

15mm~2)of dural sac cross-sectional area to values smaller than 75 mm~2 was found during examination in axial loading,or if a suspected disc herniation,narrow lateral recess,narrow intervertebral foramen,or intraspinal synovial cyst changed to being obvious at the axial loading examination,they were regarded as additional information.Results After axial loading CT examination,AVI was found in 16 of 40 patients.A significant decrease of dural sac area was found in 13 patients.Intervertebral disc herniation was more severe in 7 patients,lateral recess or interverbral foramen narrowed in 4 patients,no intraspinal synovial cyst was found.After axial loading MRI examination,AVI was found in 19 of 60 patients.A significant decrease of dural sac area was found in 13 patients.Intervertebral disc herniation became severe in 10 patients,lateral recess or interverbral foramen narrowed in 8 patients,no intraspinal synovial cyst was found.AVI was found in 32 of 79(40.5%)patients with sciatica and 2 of 20(10.0%)patients with low back pain(?~2=7.45 P

Objective To analyze the classification,MR manifestations,and the pathological basis of solitary necrotic nodule of the liver(SNN)in order to evaluate MRI as a diagnosing tool Methods The MR appearances of 9 cases with pathologically proved SNN were analyzed and correlated with the classification and pathological appearances.Relevant literature was reviewed.Results(1)Simple coagulative necrosis type(5 cases):The signal of lesions was hypo-intense or iso-intense on both T_1-and T_2- weighted images.After Gd-DTPA administration,the internal part of the lesions showed no enhancement,while the thin capsule of the lesions demonstrated mild or moderate delayed enhancement. These lesions,proved by pathology,were composed of central coagulative necrotic core and a peripheral hyaline fibrosis capsule.(2)Coagulative necrosis aceompanied by liquefactive necrosis type(1 case):On T_1-weighted images,the signal of hypo-intensity was found within these lesions and even lower signal intensity was found in the central area of larger lesions.On T_2-weighted images,the lesions had a bright core and a peripheral hypointensive or isointensive area.After Gd-DTPA administration,the internal part of the lesions showed no enhancement,while the thin capsule of the lesions demonstrated mild or moderate delayed enhancement.These lesions had a central coagulative necrosis core interleaved by slit- like liquefactive necrosis foci,and peripherally a thin capsule of hyaline fibrosis proved by pathology.(3)Multi-nodular fusion type,(3cases):On T_1-weighted images,the lesions were of hypointensive or isointensive signal and had multiple septa of isointensive signal.On T_2-weighted images,the lesions were of hypointensive or isointensive signal and had multiple septa of hyperintensive or isointensive signal.After Gd-DTPA administration,No enhancement was found except mild or moderate delayed enhancement found in the thin capsule and septa.These lesions were composed of central coagulative necrosis area and a peripheral hyaline fibrosis capsule with multiple internal septa proved by pathology.Conclusion MRI apperances can reflect the classification and pathological features of solitary necrotic nodule of the liver.

Objective To evaluate the potential utility of PⅢpeptide in anti peritoneum metastasis in gastric carcinoma cells with high peritoneal metastasis potential(GC9811 P).Methods The adhesion and invasion inhibitory effects of PⅢpeptide on GC9811-P cells were detected by in vitro matrix adhe- sion and cell invasion experiments.By using nude mice metastatic model of human gastric cancer,the effects of PⅢpeptide on peritoneal metastasis of gastric cancer GC9811 P were evaluated.Mice were randomly divided into the experimental(GC9811-P+peptide PⅢgroup)and control groups(GC9811-P +0.9% NaCl solution group),12 mice in each group.At the exhaustion time after inoculation,mice were sacrificed to observe the incidence of peritoneal metastasis,the number of the metastasis foci and the volume of primary tumor.Results Two hours after 40?g PⅢpeptide incubation,the adhesion in hibitory rate reached 86.30%.The adhesion inhibitory effects were in a time dependent manner.The in- vasion inhibitory effects became apparent(81.4%)48 hours after PⅢpeptide insult.After the GC9811- P cells were orthotopic implanted in nude mice and treated with PⅢpeptide,the number of peritoneal metastatic nodes were significantly reduced as compared with control group(3.2?6.5 vs.26.3?5.2) ( P＜0.01).But the mass of primary tumor were (1.9?1.2) g in PⅢpeptide treated group and (2.1?1.0) g in the control group,no difference was noted between two groups(P＞0 05 ).Conclusion PⅢpeptide can markedly inhibit the adhesion,invasion and peritoneal metastasis of gastric carcinoma cell line GC29811-P with high peritoneal metastasis potential

OBJECTIVETo investigate polymorphisms of killer cell immunoglobulin-like receptor gene (KIR) in renal transplant recipients from southern Zhejiang.

METHODSKIR genotypes were analyzed by PCR-SSP in 416 renal transplant recipients, and the genotype frequencies were compared with populations from Eastern China and worldwide.

RESULTSAll 16 known KIR genes were detected in the renal transplant recipients, and KIR2DL4, 3DL2-3, 3PD1 were found in all. As a pseudogene, 2DP1 has a high genotype frequency (99%). The frequencies of KIR2DL1, 2DL3, 3DL1, 2DS4 have ranged from 92.1% to 98.8%. Compared with 11 groups in Eastern China and other countries, the KIR2DL2 phenotype frequency was higher (34.6%) than those of Shanghai, Zhejiang and Jiangsu populations (P<0.05). Among 41 genotypes, three have not been reported previously. The most common genotype was AA1, with a frequency of 43.51%, which was significantly lower than those of Jiangsu and Northern Zhejiang.

CONCLUSIONRenal transplant recipients from southern Zhejiang share similar features with Eastern China Han population with regard to KIR polymorphisms, but also have unique frequencies for KIR genotypes.

Adolescent ; Adult ; Aged ; China ; Female ; Gene Frequency ; Genotype ; Humans ; Kidney Transplantation ; methods ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, KIR ; genetics ; Young Adult

OBJECTIVETo develop a double antibody sandwich ELISA assay for quantitative determination of recombinant human interferon alpha1b.

METHODSMouse monoclonal antibodies with different binding site on rIFN-alpha1b were screened to select optimized candidates as coating and HRP-labeled index antibodies respectively. And a double antibodies sandwich ELISA was assembled; the reliable lower detection limit, specificity, accuracy and reproducibility were evaluated and validated.

RESULTSThe quantitative sandwich ELISA had a reliable lower detection limit of 10 ng/ml, with a liner detection range 10-100 ng/ml (R2 = 0.992), variation coefficient inter-plates is less than 10%.

CONCLUSIONThe developed sandwich ELISA was a sensitive and specific, accuracy and reproducibility method for quantitative determination of recombinant human interferon alpha1b in final product.

Animals ; Antibodies, Monoclonal ; analysis ; Enzyme-Linked Immunosorbent Assay ; instrumentation ; methods ; Humans ; Interferon-alpha ; blood ; Mice ; Mice, Inbred BALB C

OBJECTIVETo evaluate the value of brain natriuretic peptide (BNP) in estimating risk stratification in patients with acute myocardial infarction (AMI) and to determine the relationship between BNP and adverse cardiac events after AMI.

METHODSThe 135 subjects were selected into the study, including 25 healthy subjects and 110 patients with a first AMI. The plasma concentrations of BNP were measured at two to four days after infarction in patients and healthy controls. Left ventricular function was evaluated by echocardiography with the parameters of left ventricular ejection function (LVEF) after 3 months. Patients were followed up at 12 months. The main outcome measures were heart failure, left remodeling, mortality and other adverse cardiac events at one year.

RESULTSPlasma BNP concentrations in patients with AMI were much higher than those in the health control people (416.7 +/- 208.0 ng/L versus 61.8 +/- 34.1 ng/L, P < 0.01). The BNP count ranged from 5 to 2500 ng/L in AMI patients. There was no association between the BNP count and mortality rate. The development of new congestive heart failure (CHF) was associated with a higher BNP count (P = 0.02). The development of any of the clinical end points (death/CHF/shock) occurred more frequently in patients with a higher BNP count (13.8% for BNP count of < 100 ng/L, 39.1% for BNP count of 100 - 200 ng/L, 43.3% for BNP count of 200 - 400 ng/L, 46.4% for BNP count of > 400 ng/L; P = 0.019). Plasma BNP concentrations remained independently associated with the development of clinical end points in multivariable model that adjusted for potential confounding variables.

CONCLUSIONThe results of the present study confirm that the elevated BNP count related to the risk stratification and prognosis in patients with AMI. Elevations in BNP count are associated with a higher incidence of new CHF and adverse clinical outcomes after AMI. It could serve as a strong predictor for the subsequent development of poor outcomes in AMI patients.

Adult ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; blood ; diagnosis ; Natriuretic Peptide, Brain ; blood ; Prognosis

OBJECTIVETo investigate the impact of adding folic acid, vitamin B(12) and probucol to standard antihypertensive medication on plasma homocysteine (Hcy) and asymmetric dimethylarginine (ADMA), serum NO and eNOS of essential hypertensive patients.

METHODA total of 120 patients with hypertension were randomly divided to three groups (n = 40 each): group 1 (standard medication), group 2 (adding folic acid 5 mg/day and vitamin B(12) 500 µg twice daily) and group 3 (adding folic acid 5 mg/day and vitamin B(12) 500 µg twice daily and probucol 500 mg twice daily). Plasma Hcy and ADMA, serum NO and eNOS levels were observed at baseline, 2 and 12 weeks after various therapy.

RESULTSIn group 1, concentrations of plasma Hcy [(23.06 ± 14.15) µmol/L, (23.67 ± 12.31) µmol/L, (23.25 ± 11.64) µmol/L], ADMA [(0.21 ± 0.12) µmol/L, (0.23 ± 0.13) µmol/L, (0.21 ± 0.09) µmol/L] and serum NO [(64.14 ± 15.07) µmol/L, (65.29 ± 15.04) µmol/L, (65.32 ± 13.58) µmol/L], eNOS [(20.02 ± 4.50) µg/L, (20.79 ± 4.03) µg/L, (19.82 ± 5.70) µg/L] remained unchanged during the 12 weeks therapy (all P > 0.05). In group 2, concentrations of plasma Hcy [(12.54 ± 6.49) µmol/L] and ADMA[(0.18 ± 0.07) µmol/L] were significantly decreased after the treatment of 12 weeks than the treatment baseline value [(21.51 ± 7.82) µmol/L, (0.20 ± 0.12) µmol/L] and 2 weeks value[(19.38 ± 8.14) µmol/L, (0.21 ± 0.12) µmol/L], however the concentrations of serum NO and eNOS showed contrary results of the Hcy and ADMA's. (all P < 0.05). In group 3, similar changes occurred at 2 weeks after therapy (P < 0.05 2 weeks vs. baseline and 12 weeks vs. 2 weeks). Plasma ADMA level was positively correlated with Hcy at baseline (r = 0.546, P < 0.05).

CONCLUSIONSSupplementation of folic acid, VitB(12) and/or probucol helps to improve endothelial function and reduce plasma Hcy and ADMA levels in patients with hypertension.

Aged ; Antihypertensive Agents ; therapeutic use ; Arginine ; analogs & derivatives ; blood ; Female ; Folic Acid ; therapeutic use ; Homocysteine ; blood ; Humans ; Hypertension ; blood ; drug therapy ; Male ; Middle Aged ; Nitric Oxide ; blood ; Nitric Oxide Synthase Type III ; blood ; Plasma ; metabolism ; Probucol ; therapeutic use ; Vitamin B 12 ; therapeutic use ; Vitamin B Complex ; therapeutic use ; Vitamins ; therapeutic use

OBJECTIVETo observe the effects of combined beta(1) adrenergic receptor (AR) antagonist with beta(2)AR agonist therapy on cardiac function and cardiomyocyte apoptosis in heart failure rats.

METHODSHeart failure was induced by isoproterenol and rats were randomly divided into metoprolol group (50 mg/kg twice daily/gavage, n = 11), combined treatment group (fenoterol 125 microg/kg and metoprolol 50 mg/kg twice daily/gavage, n = 11) and placebo group (saline, n = 10), another normal 9 male Wistar rats served as control group. After 8 weeks' treatment, cardiac function, apoptosis index (AI), Caspase-3 activity, expression levels of bcl-2 and bax protein, organ weight/body weight and collagen volume fraction (CVF) were evaluated.

RESULTS(1) Left ventricular end diastolic dimension, left ventricular end systolic dimension and E/A ratio were significantly increased and fractional shortening, ejection fraction significantly reduced post isoproterenol (all P < 0.05 vs. control) and these changes were significantly attenuated by metoprolol alone (all P < 0.05 vs. placebo) and further attenuated by the metoprolol and fenoterol combination therapy (all P < 0.05 vs. placebo and metoprolol). (2) Left ventricular weight to body weight ratio, lung weight to body weight ratio and CVF were also significantly reduced in metoprolol and combined treatment group than those in placebo group (all P < 0.01). (3) Compared with placebo group, AI and Caspase-3 activity were significantly lower in metoprolol group (all P < 0.01 vs. placebo) and further reduced in combined treatment group (all P < 0.01 vs. metoprolol). (4) The expression level of bax protein was significantly lower in metoprolol group while bcl-2/bax significantly higher than those in placebo group. These changes were more significant in combined treatment group (all P < 0.01 vs. metoprolol).

CONCLUSIONSbeta(1)AR antagonist in combination with beta(2)AR agonist further improved the cardiac function and prevented cardiac remodeling compared with using beta(1)AR antagonist alone in heart failure rats. Downregulated bax and upregulated bcl-2/bax expressions might contribute to the observed beneficial therapy effects by reducing cardiomyocyte apoptosis in these animals.

Adrenergic beta-1 Receptor Antagonists ; Adrenergic beta-2 Receptor Agonists ; Adrenergic beta-Agonists ; pharmacology ; therapeutic use ; Adrenergic beta-Antagonists ; pharmacology ; therapeutic use ; Animals ; Apoptosis ; drug effects ; Drug Therapy, Combination ; Heart Failure ; drug therapy ; Male ; Myocytes, Cardiac ; cytology ; Rats ; Rats, Wistar ; Ventricular Remodeling