To investigate the relationship between HLA-DQB1* alleles and major beta-thalassemia, the HLA-DQB1* loci typing was performed with polymerase chain reaction-sequence specific primer (PCR-SSP) in 42 unrelated (unconsanguineous) patients with major beta-thalassemia and 45 normal control individuals in Guangdong Province. Results showed that the frequency of HLA-DQB1*06 allele in patient group (19.0%) was higher than that in the control group (4.4%) kappa(2) = 8.961, p < 0.01). Our data suggests that HLA-DQB1*06 allele is associated with pathogenesis of the major beta-thalassemia in Guangdong area.
Alleles ; Asian Continental Ancestry Group ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; HLA-DQ Antigens ; genetics ; HLA-DQ beta-Chains ; Humans ; Male ; beta-Thalassemia ; genetics

OBJECTIVETo determine whether the matrix metalloproteinase 9 gene (MMP9) polymorphism is associated with the onset or progression of adolescent idiopathic scoliosis (AIS) in Chinese Han female.

METHODSThree single nucleotide polymorphisms (SNPs) (rs17576, rs2250889, rs1805088) were genotyped through TaqMan-based real-time PCR assay in 190 AIS patients and 190 controls, all of whom were females from Chinese Han population with matched age. Analyses performed included Hardy Weinberg equilibrium test, Pearson chi-square test, Logistic regression analysis, linkage disequilibrium analysis and haplotype analysis. The mean maximum Cobb angles with different genotypes in case-only dataset were also compared.

RESULTSAll 3 SNPs have reached Hardy-Weinberg equilibrium in the controls. Genotype and allele frequencies of all SNPs were found similar between cases and controls by Pearson chi-square test and Logistic regression. Genotype-phenotype analysis showed that patients with CC genotype in rs2250889 featured larger maximum Cobb angles.

CONCLUSIONMMP9 may not be a predisposition gene of AIS in Han female. However, homozygous mutation in rs2250889 can render scoliosis more severe, implying that MMP9 defect may result in deterioration of AIS.

Adolescent ; Asian Continental Ancestry Group ; genetics ; Child ; China ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Matrix Metalloproteinase 9 ; genetics ; Phenotype ; Polymorphism, Single Nucleotide ; genetics ; Scoliosis ; genetics

BACKGROUNDSeveral studies have evaluated the association between polymorphisms of thymidylate synthase (TS) and cancer risk in diverse populations but with conflicting results. By pooling the relatively small samples in each study, it is possible to evaluate the association using a meta-analysis.

METHODSA comprehensive search was conducted to identify all case-control studies on TS on a 28-bp tandem repeats in 5'untranslated region (5'UTR) and a 6-bp insertion (ins) and deletion (del) mutation in 3'UTR of the gene and cancer risk. Meta-analysis was conducted using a fixed and random effect model.

RESULTSOur meta-analysis on a total of 13 307 cancer cases and 18 226 control subjects from 37 published case-control studies showed no significant association between the risk of cancer and the 5'UTR 28-bp tandem repeats polymorphism (3R/3R vs. 2R/2R: OR = 1.06, 95%CI, 0.93 - 1.20) or the 3'UTR 6-bp ins/del polymorphism (del6/del6 vs. ins6/ins6: OR = 0.93, 95%CI, 0.81 - 1.08) with significant between-study heterogeneity. In the cancer type- and ethnic subgroup-stratification analyses, we did not find any association between TS polymorphisms and cancer risk either.

CONCLUSIONTS 5'UTR 28-bp tandem repeats and 3'UTR 6-bp ins/del polymorphisms may not be associated with cancer risk.

3' Untranslated Regions ; genetics ; 5' Untranslated Regions ; genetics ; Case-Control Studies ; Genetic Predisposition to Disease ; genetics ; Humans ; Neoplasms ; epidemiology ; genetics ; Polymorphism, Genetic ; genetics ; Tandem Repeat Sequences ; genetics ; Thymidylate Synthase ; genetics

OBJECTIVEChronic graft versus host disease (cGVHD) is the most common late complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and it represents the major cause of mortality in long-term survivors. Over the past decade, although conventional therapy has achieved complete responses in approximately 50% of patients, the prophylaxis and treatment of cGVHD are still not satisfactory. In the late years, utilization of new immunosuppressant such as tacrolimus (FK506), mycophenolate mofetil (MMF) on cGVHD improved the curative effects. This study tried to analyze the results of combination of methylprednisolone (MP), MMF and FK506 or cyclosporine A (CSA) as immunosuppressive therapies for cGVHD and to explore the effective regimen for children.

METHODSForty-five patients received allo-HSCT. Among them 32 received UCBT and 13 received PBSCT. The conditional regimen mainly consisted of busalphan, cyclophosphamide, antihuman thymocyte globulin, fludarabin, melphalan, thiotepa and total lymph node irradiation. Prophylaxis of GVHD consisted of CSA, MP and MMF. Patients with cGVHD received a regimen with combination of MP, MMF and FK506 or CSA.

RESULTSSeventeen out of 32 patients who received UCBT were engrafted. while 9 out of 13 patients who received PBSCT were engrafted. Nine cases of the 30 engrafted patients developed cGVHD (morbidity 30%). Among the 17 patients who received UCBT, 3 developed cGVHD (18%). Among the 13 patients who received PBSCT, 6 developed cGVHD (46%). Six cGVHD continued from aGVHD (6/9). One patient was given CSA plus MMF, and 8 were given three-drug regimen with MP, MMF and FK506. The overall response rate was 100%. Two patients died of CMV-IP or septicemia (mortality 20%). Seven (78%) patients survived (event free survival, EFS) longer than 3 years. The side effects included hepatotoxicity, nephrotoxicity, hypertension, articular capsulitis and arrhythmia. The main complication and the major causes of death were infection.

CONCLUSIONThe incidence of cGVHD is low in children. The incidence of cGVHD after PBSCT is higher than that after UCBT. aGVHD is a highly dangerous factor. Combined therapy of MP plus MMF and FK506 or CSA is safe and effective for the treatment of cGVHD in children.

Child ; Child, Preschool ; Chronic Disease ; Drug Therapy, Combination ; Female ; Graft vs Host Disease ; drug therapy ; epidemiology ; prevention & control ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Incidence ; Male ; Methylprednisolone ; administration & dosage ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; Tacrolimus ; administration & dosage

This study was aimed to investigate the therapeutic efficacy of rabbit anti-thymocyte globulin (r-ATG) combined with cyclosporine A (CsA) and to analyse the efficacy-related factors in children with aplastic anemia (AA). Twenty five AA children treated with r-ATG [3.5 mg/(kg·d)×5 days] combined with CsA were analyzed retrospectively. The lymphocyte subgroups, CD4(+)/CD8 ratio and expression of CD55, CD59 on surface of neutrophils and erythrocytes in peripheral blood were detected by direct immunofluorescence method and flow cytometry; the responsive time, effective rate, adverse effects and infections after immunosuppressive therapy (IST) were analyzed; the distribution of T-lymphocyte subgroups in IST-effective and IST-uneffective groups was compared, and therapeutic efficacy-related factors were evaluated. The results showed that the response to treatments was found in 21 out of 25 cases, the total responsive rate was 84.0%; the response time was 3 - 6 months, average of 4 months; the effective rates in month 3, 6, 9, 12 after treatment were 56.0%, 72.0%, 80.0% and 84.0% respectively. The AA children with age ≥ 5 years old, course of disease < 6 months and absolute neutrophil value ≥ 1.5 ×10(9)/L on 30 days after IST had good curative effect; the effective rate in AA children with age ≥ 5 years old, course of disease < 6 months, high or reverse ratio of CD4(+)/CD8(+) and absolute neutrophil value ≥ 1.5×10(9)/L after IST was higher than that in AA children with age < 5 years old, course of disease ≥ 6 months, normal ratio of CD4(+)/CD8(+) and absolute neutrophil value after IST < 1.5×10(9)/L (94.4% vs 57.1%, 90.4% vs 50.0%, 94.1% vs 62.5%, 94.1% vs 62.5%) (P < 0.05). The high effective rate was observed in AA children with decrease of CD55 and CD59 expression, but there was no significant difference (P > 0.05) as compared with normal expression of CD55, CD59. It is concluded that the treatment using r-ATG (3.5 mg/kg·d × 5 d) combined with CsA is a safe and effective for children with AA. Age, course of disease and absolute neutrophil value on 30 days after IST are the main factors affecting curative affect.
Adolescent ; Anemia, Aplastic ; drug therapy ; Antilymphocyte Serum ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Cyclosporine ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Lymphocyte Count ; Lymphocyte Subsets ; Male ; Retrospective Studies ; Treatment Outcome

Fcγ receptorIIIa (FcγRIIIa) polymorphism was considered to influence clinical response to therapeutic monoclonal antibody (MAb) against cancer, which is suggested to affect MAb binding and MAb-dependent NK cell-mediated cytotoxicity. The purpose of this study was to examine the FcγRIIIa gene polymorphisms in healthy children and in children with hematological malignancy, and to explore its possible effect on MAb in children with hematological malignancies. 43 healthy children (H) and 20 pediatric patients with hematological malignancies (HM) were enrolled in this study. DNA was isolated from peripheral blood, and then nest-polymerase chain reaction-restriction fragment length polymorphism (nest-PCR and PCR-RFLP) was used to determine the FcγRIIIa-158 genotypes in each groups of subject, digested fragments were subjected to electrophoresis on 15% PAGE. The results showed that there were a higher frequencies of FcγRIIIa-158V/F in H and HM group (72.1% and 75.0% respectively), the frequencies of FcγRIIIa-158V/V were 27.9% and 25.0% in H and HM group respectively, but there was no FcγRIIIa-158F/F in the two groups. No significant difference in distribution of the FcγRIIIa-158 genotype was found between HM and H groups (p > 0.05). It is concluded that FcγRIIIa-158V/F is more frequent, while FcγRIIIa-158V/V is less, but FcγRIIIa-158F/F is very rare in both groups. No significant difference of FcγRIIIa polymorphism distribution is found between healthy and hematological malignancy groups.
Adolescent ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Genotype ; Hematologic Neoplasms ; genetics ; Humans ; Male ; Polymorphism, Genetic ; Receptors, IgG ; genetics

Fcgamma receptor IIIa (FcγRIIIa) polymorphisms is considered to influence clinical response to therapeutic monoclonal antibody (McAb) in cancer, most people believe it can affect McAb binding, and McAb-dependent NK cell-mediated cytotoxicity. This study was purposed to determine the difference of antibody-dependent cell-mediated cytotoxicity (ADCC) effects mediated by different FcγRIIIa NK cells. The FcγRIIIa genotypes were detected by nest-PCR, the target cells (Raji cells) were stained with 5- (and 6-) carboxyfluorescein diacetate succinimidyl ester (CFSE), cultured with effector cells with different FcγRIIIa genotypes, and finally stained with propidium iodide (PI); the CD20 expression of Raji cells were tested by flow cytometry and cytotoxic index was calculated as well. The results indicated that the ADCC cytotoxic indexes of NK cells with FcγRIIIa-158V/V and FcγRIIIa-158V/F were 69.05±2.38% and 39.63±3.86% respectively, as compared with NK cells with FcγRIIIa158 V/V, ADCC effect of NK cells with FcγRIIIa-158 on Raji cells was obviously weakened with significant difference (p<0.05). It is concluded that FcγRIIIa polymorphism can influence ADCC activity of NK cells, ADCC activity of NK cells with FcγRIIIa-158V/V is higher than that of NK cells with FcγRIIIa-158V/F.
Antibodies, Monoclonal ; pharmacology ; Antibodies, Monoclonal, Murine-Derived ; pharmacology ; Antibody-Dependent Cell Cytotoxicity ; drug effects ; Cell Line ; Genotype ; Humans ; Killer Cells, Natural ; drug effects ; Polymorphism, Genetic ; Receptors, IgG ; genetics ; Rituximab

OBJECTIVETo prepare cryptotanshinone (CT)-cyclodextrin inclusion compound and improve dissolution of CT.

METHODInclusion ratio was determined by plotting the phase solubility curve of CT versus hydroxypropyl-beta-cyclodextrin (HPCD). CT-cyclodextrin inclusion compound was made by wet grinding method. Properties of the inclusion compound was investigated by in vitro dissolution test, DTA and IR spectrum.

RESULTInclusion ratio of CT versus HPCD was 1:1. Dissolution of CT-HPCD inclusion compound at 45 min was 21.6 times of material drug.

CONCLUSIONDissolution of CT was improved remarkably in CT-HPCD inclusion compound. The complexation force of the inclusion compound was hydrogen bond formed by carbonyl group of CT and hydroxyl group of HPCD.

2-Hydroxypropyl-beta-cyclodextrin ; Biological Availability ; Drug Carriers ; Drugs, Chinese Herbal ; chemistry ; Phenanthrenes ; chemistry ; isolation & purification ; Salvia miltiorrhiza ; chemistry ; Solubility ; Technology, Pharmaceutical ; methods ; Time Factors ; beta-Cyclodextrins ; chemistry

OBJECTIVETo observe the effects of antioxidation and ceramide content of improved prescription of Didang-tang (IPDT) on exprimental atherosclerosis(AS) rabbits.

METHODPlasm Superoxide Dismutase(SOD) activity was detected with micro-content fast detecting method, Plasm Malondialdehyde(MDA) content with improved BaMuGuoFu method, and Aortic Ceramide (CER) content with thinlayer scanning.

RESULTIPDT could effectivly improve plasma SOD activity and decrease plasma MDA content and decrease aortic CER content.

CONCLUSIONIPDT on exprimental AS is related to the improvement of antioxidation and decrease of CER content.

Animals ; Antioxidants ; pharmacology ; Arteriosclerosis ; metabolism ; Ceramides ; metabolism ; Cinnamomum ; chemistry ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Leeches ; chemistry ; Male ; Materia Medica ; pharmacology ; Plants, Medicinal ; chemistry ; Rabbits ; Rheum ; chemistry

OBJECTIVETo study the clinical features and the incidence of early infectious complications following children hematopoietic stem cells transplantation (HSCT).

METHODSThe clinical data of 29 cases with early infectious complications following HSCT was retrospectively analyzed.

RESULTSThe incidence of early infectious complications following HSCT in 31 children (including 22 cord blood transplantation and 9 peripheral blood stem cells transplantation) was 94% (29/31). The first occurrence of the early infectious complications was at a median of 6 (0 - 22) days, the peak time of incidence was at a median of 4 - 7 days post transplantation. The duration of the first early infectious complications was at a median of 9 (3 - 20) days. The occurrence of the second early infectious complications was at a median of 19 (13 - 27) days. For all of the 29 children, when they developed early infectious complications their absolute neutrophil counts (ANC) were all > 0.5 x 10(9)/L. The most common infectious sites were the digestive tract (oral and gastro-intestinal mucositis) and then the respiratory tract. Gram negative blood infections were quite frequent and Pseudomonas aeruginosa was common in the oral-pharynx discharge cultures. Two children had Mycoplasma pneumonia infections and there were 4 incidences with fever but no definite infectious foci. The incidence and duration of early infectious complications following hematopoietic stem cells transplantation were associated with the duration of neutropenia. The source and the MNCs dose of the graft, the difference of conditioning regimen and GVHD prophylaxis method did not have a significant impact on the incidence and duration of early infectious complications. Antibiotic prophylaxis (including Tienam) could delay the occurrence of the early infections significantly.

CONCLUSIONThe incidence and duration of early infectious complications following hematopoietic stem cells transplantation were directly associated with the duration of neutropenia. Tienam regimen could postpone the early infections incidence and had effect of preventing the early infectious complications.

Adolescent ; Antibiotic Prophylaxis ; Child ; Child, Preschool ; China ; epidemiology ; Cilastatin ; therapeutic use ; Drug Combinations ; Female ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Imipenem ; therapeutic use ; Incidence ; Infection ; drug therapy ; epidemiology ; etiology ; Leukemia ; therapy ; Male ; Retrospective Studies ; Time Factors