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Objective:To investigate the effects of Notch1 signaling on histone acetylation of Foxp3 gene and its roles in regulating regulatory T (Treg) cells in children with acute B-cell precursor lymphoblastic leukemia (BCP-ALL).Methods:Blood samples were collected form 38 children with BCP-ALL before treatment and 15 age-matched healthy children (control group). Flow cytometry was performed to detect the proportion of peripheral blood CD4 + CD25 hiFoxp3 + Treg cells and the expression of Foxp3, cytotoxic lymphocyte antigen 4 (CTLA4), glucocorticoid-induced tumor necrosis factor receptor (GITR), CD39 and Notch1 at protein level. Histone 4 acetylation (H4Ac) at Foxp3 gene promoter and the binding abilities of Foxp3 gene promoter to NICD1 and p300 in CD4 + T cells were measured by chromatin immunoprecipitation. Quantitative real-time PCR was performed to detect the expression of Foxp3, presenilin 1 (PSEN1), mastermind-like transcriptional coactivator 1 (MAML1), SKI-interacting protein (SKIP), F-box and WD40 domain protein 7 (FBXW7), glycogen synthase kinase-3 beta (GSK3β) and IKAROS at mRNA level in CD4 + T cells. The concentrations of TGF-β and IL-10 in plasma were evaluated by ELISA. Results:(1) The proportion of peripheral blood CD4 + CD25 hiFoxp3 + Treg cells, the expression of differentiation- and function-associated molecules (Foxp3, CTLA4, GITR and CD39) and the concentrations of TGF-β and IL-10 in plasma were higher in the BCP-ALL group than in the control group ( P<0.05). (2) In children with acute BCP-ALL, H4Ac at Foxp3 promoter and the binding abilities of Foxp3 gene promoter to NICD1 and p300 were significantly increased as compared with those in control group( P<0.05). The binding abilities of Foxp3 gene promoter to NICD1 and p300 were positively correlated with the expression of Foxp3 at mRNA level ( r=0.58 and 0.46, both P<0.05). After competitive inhibition, the three aforementioned indexes in the acute BCP-ALL group were significantly lower than those in untreated group ( P<0.05); the binding ability of Foxp3 gene promoter to NICD1 in the control group was also significantly lower than that in untreated control group ( P<0.05), but no statistical differences in the other two indexes were found between the control groups with or without treatment ( P>0.05). ⑶ Compared with the control group, the expression of Notch1, PSEN1, MAML1 and SKIP in CD4 + T cells were elevated significantly ( P<0.05), while the transcription level of negative regulatory factor FBXW7 was decreased remarkably in children with acute BCP-ALL ( P<0.05). No statistical differences in the expression of GSK3β or IKAROS were found between the two groups ( P>0.05). Conclusions:Overactivation of Notch1 signaling caused by low expression of FBXW7 might be the key factor resulting in histone 4 hyperacetylation at foxp3 gene promoter and Treg cell dysfunction in children with acute BCP-ALL.
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Objective To analysis the clinical characteristics and the long-term effect of children with acute lymphoblastic leukemia (ALL).Methods From 2005 to 2010,80 newly diagnosed ALL children were enrolled and treated with protocol based on ALL-BFM2002.The five-years overall survival (OS)and event-free survival(EFS) were analyzed by the method of Kaplan-Meier.Results For the 80 patients,male to female ratio is 1.22∶1.The median age was 4.3 years.33 were in standard risk(41.2％),37 were in medium risk(46.3％),and 10 were in high risk(12.5％).22 had white blood cell count ≥20 x 109/L(27.5％).three patients with BCR-ABL translocation(3.8％),one patient with MLL gene rearrangement(1.3％),17 patients with TEL-AML translocation (21.3％).During induction therapy,79 patients (98.8 ％) achieved complete remission(CR).The five-years OS and EFS were (85.9 ± 4.0) ％ and (79.2 ± 4.7) ％ respectively.The five-years EFS:SR group (86.6 ± 6.4) ％,IR group (81.1 ± 6.4) ％,HR group (48.0 ± 16.4) ％.The difference among risk groups was statistically significant(x2 =7.03,P ＜0.05).12 patients relapsed(15.0％),the median time from diagnosis to relapse was 23.5 months.11 patients died (13.8 ％).Conclusion According to stratification by risk factors and risk-adapted therapy,the quality of ALL children's life had improved.
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Objective:To investigate the association between glutathione S-transferase pi (GSTP1) gene polymorphism and toxici-ties related to high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Methods:GSTP1 genotypes and allelic frequencies in 51 children with ALL were determined by Nest PCR, denaturing gel gradient electrophoresis (DGGE), and DNA sequencing. HD-MTX adverse reactions were analyzed using the National Cancer Institute Common Toxicity Criteria (NCICTC). Results:We identified three SNPs of GSTP1, including rs1695 (A313G), rs1138272 (G439T), and rs4891 (T555C). The wild types, het-erozygous types, and homozygous types of GSTP1 rs1695/rs4891 polymorphisms were detected in 32 cases (62.7%), 16 cases (31.4%), and 3 cases (5.9%), respectively. GSTP1 rs1695/rs4891 polymorphisms included only one heterozygous type and one homozygous type. The allele frequencies of the three SNPs were 21.6%, 2.9%, and 21.6%. The AG+GG/TC+CC genotype of GSTP1 rs1695/rs4891 was associated with decrease in the odds of peripheral hemoglobin (OR=0.25, 95%CI=0.06-1.00, P=0.049). The AG+GG/TC+CC genotype of GSTP1 rs1695/rs4891 in standard and intermediate-risk ALL children was significantly correlated with higher odds of gastrointesti-nal toxicity (OR=0.125, 95%CI=0.02-0.78, P=0.026). Conclusion:GSTP1 rs1695 (A313G)/rs4891 (T555C) gene polymorphism is as-sociated with the reduction of peripheral hemoglobin in ALL children and with the odds of gastrointestinal toxicity in standard and inter-mediate-risk ALL children who receive high-dose methotrexate.
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Objective To investigate the changes of CD4 +CD25highFoxp3 +regulatory T (Treg) cells and their significance in immune escape of childhood B-cell acute lymphocytic leukemia ( B-ALL ) . Methods Forty-two children with B-ALL and twenty-eight age-matched healthy children were enrolled in this study.Flow cytometry analysis was performed to evaluate the proportion of CD 4 +CD25high Foxp3 +Treg cells as well as CD4 +CD25high ICOS+Foxp3 +and CD4 +CD25high ICOS-Foxp3 +subsets in peripheral blood samples.The expression of associated molecules including IL-10, TGF-β, IL-35, TGF-βRII, ICOS and CD28 at protein level were also measured by flow cytometry analysis .The transcription level of Smad3/4, TIEG1 and Itch by CD4 +T cells were determined by quantitative real-time PCR.The concentration of TGF-βin plasma was detected by enzyme-linked immunosorbent assay.Results (1)The proportion of CD4 +CD25highFoxp3 +Treg cells in children with B-ALL were significantly higher than those of health subjects (P0.05).(3)The concentra-tion of TGF-βin plasma from children with B-ALL were higher than those from control group [ ( 25 .83 ± 12.65) ng/ml vs (8.59 ±5.73) ng/ml, P<0.05].The expression of TGF-βRII and its associated mole-cules (Smad3/4, TIEG1 and Itch) by CD4 +T cells were significantly up-regulated.Moreover, an increased expression of ICOS and CD28 by CD4 +CD25highFoxp3 +Treg cells were also observed in children with B-ALL (P<0.05).Conclusion The hyper-activity of TGF-β, ICOS and CD28 signaling might be closely associ-ated with the increased proportion of CD4 +CD25high Foxp3 +Treg cells and the imbalance of its subsets in children with B-ALL.
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Objective To investigate the role of fluid therapy in treatment of septic shock in children.Methods A total of 48 pediatric patients with septic shock were enrolled.Twenty-seven patients were treated with volume expansion and 21 patients were treated with fluid resuscitation.There were no differences in use of antibiotics,inotropic and vasoactive agent in two groups.The time needed for haemodynamic stability,occurrence of pulmonary edema.length of PICU stay,and mortality were compared between two groups.Results Compared with volume expansion group,the time needed for haemodynamic stability significantly decreased in fluid resuscitation group ((216.10± 168.13) minutes vs (121.63 ± 75.59) minutes) (P 0.05) .Compared with volume expansion group,length of PICU stay significantly decreased in fluid resuscitation group ((6.188 ±3.250) days vs (3.944±2.711) days,P < 0.05).Compared with volume expansion group,mortality significantly decreased in fluid resuscitation group (40.7% vs 14.3%,P < 0.05) . Conclusions Rapid fluid resuscitation was associated with early reach of haemodynamic stability,short stay in PICU,improved survival rate and no increase in the risk of complication in pediatric patient with septic shock.
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Objective To discuss the tumor suppressing effect of cadmium chloride on S180 sarcoma,and to explore its favoriable dosage.Methods The mouse models bearing S180 sarcoma were treated with cadmium chloride with dosages of 0.25,1.00 and 4.00 mg?kg-1,the anti-tumor effect was evaluated by calculating of tumor weight;spleen and thymus indexes,carbon phage assay,lymphocyte transformed assay and hematolysis assay were used to measure the effect of cadmium chloride on immune function.Results Cadmium chloride with varied dosage of 0.25,1.00 and 4.00 mg?kg-1 inhibited the growth of S180 sarcoma,the tumor weights in cadmium chloride groups were significantly lower than that in control(P
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Objective To investigate the suppressing effect of cadmium chloride on proliferation of hepatocarcinoma,and to discuss the mechanism for the difference of cadmium chloride between normal and tumor tissue.Methods Hepatocarcinoma cell lines HepG-2 and SMMC-7721 were treated with 5,10,25 and 50 ?mol?L-1 cadmium chloride for 6 h,MTT essay was used to measure the inhibition of proliferation of HepG-2 and SMMC-7721 cells;Instantaneously,HepG-2 and SMMC-7721 cells were treated with 25 ?mol?L-1 cadmium chloride for different time,the inhibition of proliferation was also measured.Athymic mice were used to establish the human hepatocarcinoma animal models,the survival day and tumor volume 8 weeks after drug administration were detected;the metallothionein(MT) levels in normal and tumor tissues were determined by immunohistochemimal staining.Results Compared with control group,5,10,25 and 50 ?mol?L1 cadmium chloride inhibited the proliferation of hepatocarcinoma cell lines(P
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Objective:To study the effectiveness and safety of different acupuncture therapies in treating Posttraumatic stress disorder(PTSD)after Wenchuan‘5.12’earthquake.And choose a desirable acupuncture therapy.Methods:A total of 276 patients were recruited in this trial and randomly divided into four groups:scalp electric acupuncture group(group A),scalp electric acupuncture with moxibustion group(group B),scalp electric acupuncture with auricular acupuncture group(group C)and paroxetine hydrochloride group(group D).Each group was treated for 12 weeks.Patients were scored using Clinicianadministered Scale for DSM-IV(CAPS),Hamilton Depression Rating Scale for Depression(HAMD),and Hamilton Anxiety Scale(HAMA).Results:The study was finished well with a balanced grouping and fine baseline.After the analysis of integrations of CAPS,HAMD,and HAMA,we found that the score differences before and after the treatment were of statistical significance in all four groups(P
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Objective: It is to investigate the efficacy of the blood-activating and orifice-opening method with acupuncture and moxibusion for treatment of vertebroarterial cervical spondylopathy. Methods: 176 cases were divided into the treatment group (89 cases) and control group (87 cases) randomly. Acupuncture on points Geshu (BL 17), Fengchi (GB 20) and Bailao (Ex-HN) was applied, and meanwhile moxibustion on points Baihui (GV 20) and Shangxing (GV 23) was applied in the treatment group, while Flunarizine was orally taken in the control group. Results: The blood-activating and orifice-opening method with acupuncture and moxibustion could significantly improve the comprehensive curative effect clinically, increase the subjective index score and the sign score significantly, and change hemodynamics obviously. Its effect was better than that of the control group. It was also found that its follow-up effect was significantly better that of the control group. Conclusion: The blood-activating and orifice-opening method with acupuncture and moxibustion has a definite effect on vertebroarterial cervical spondylopathy.
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Objective To study the feature of regional cerebral metabolism rate of glucose (rCMRglc) in patients with Alzheimer’s disease (AD) and the value of positron emission tomography (PET) scanning in diagnosis of AD. Methods 13 AD patients and 13 health controls ,Who matched in age,sex and education years,were scanned with PET. Results (1) Watching by naked eyes,there was mild decreasing of rCMRglc at parietal lobe in healthy elders. While in AD patients,there was widely decreasing of cerebral metabolism rate of glucose. The most significant region was parietal lobe, the next was temporal lobe,and the last was frontal lobe. (2) Detecting with PET and dealing with statistical parametric mapping (SPM) of 99 software,there was more significant decreasing of rCMRglc in regions 7,23,30,31 of cingulate gyrus,region 39 and 40 of pario-occipital lobe,region 20 of temporal lobe and region 6,8,9 of frontal lobe in AD group( P