AIM: To investigate the relationship between serum soluble interleukin-2 receptor (sIL-2R) level and anti-HBc in patients with chronic hepatitis B virus (HBV) infection. METHODS: Sera from 100 patients with chro...AIM: To investigate the relationship between serum soluble interleukin-2 receptor (sIL-2R) level and anti-HBc in patients with chronic hepatitis B virus (HBV) infection. METHODS: Sera from 100 patients with chronic HBV infection and 30 healthy controls were included in this study. The patients were divided into group A [HBsAg (+), HBeAg (+) and anti-HBc (+), n = 50] and group B [HBsAg (+), HBeAg (+) and anti-HBc (-), n = 50]. sIL-2R levels were determined using ELISA. HBV DNA and alanine aminotransferase (ALT) were also detected. RESULTS: Serum sIL-2R levels were significantly higher in patients with chronic HBV infection than in healthy controls. Moreover, serum sIL-2R levels were significantly higher in patients with HBsAg (+), HBeAg (+) and antiHBc (+) (976.56±213.51×10^3 U/L) than in patients with HBsAg (+), HBeAg (+) and anti-HBc (-) (393.41±189.54 ×10^3 U/L, P〈 0.01). A significant relationship was found between serum sIL-2R and ALT levels (P〈 0.01) in patients with chronic HBV infection, but there was no correlation between sIL-2R and HBV DNA levels. The anti-HBc status was significantly related to the age of patients (P〈 0.01). CONCLUSION: The high sIL-2R level is related to positive anti-HBc in chronic hepatitis B patients. Positive anti-HBc may be related to T-lymphocyte activation and negative anti-HBc may imply immune tolerance in these patients.展开更多
Objective To detect the minimal residual disease in children with B-ALL and to evaluate its clinical significance by flow cytometry. Methods 58 childhood B-ALL cases were enrolled into this study and 33 MRD analyses w...Objective To detect the minimal residual disease in children with B-ALL and to evaluate its clinical significance by flow cytometry. Methods 58 childhood B-ALL cases were enrolled into this study and 33 MRD analyses were performed after remission induction therapy.Four-color combinations of fluorochrome labeled monoclonal antibodies against lymphocyte lineage related phenotypes were used to analyze leukemic cells with flow cytometry.The cells from normal bone marrow were used as controls.The combinations of phenotypes that reflect the antigen expression differences between leukemic and normal bone marrow cells on flow cytometry were considered to be the effective phenotype combinations in the first step screening.The effective phenotype combinations were then used to monitor MRD during the disease course after therapy began. Results 58 cases of childhood B-ALL were screened for MRD effective phenotype combinations.The effective phenotype combinations were identified in 89.7% of B-ALL cases in this study.Four-color phenotype combinations were composed of CD10/CD34/CD19 plus another effective marker such as CD38,CD58,CD66c,CD21.The senstitivity of this method was 0.01%,much higher than that of microscopic inspection.In 8 cases,their bone marrow microscopic inspection results showed no remaining leukemic cells;but with flow cytometry,the percentage of leukemic cells were 5.66%,0.36%,1.43%,0.069%,1.55%,2.7%,0.028% and 0.015%,respectively.In risk stratification,all these MRD positive cases were classified into high risk group for relapse and 1 case showed early relapse within 6 months. Conclusion The application of flow cytometry in MRD measurement can significantly improve the sensitivity of detection of remained leukemic cells in childhood B-ALL,and can provide more accurate information on disease progression as well as the efficacy of therapy,thus facilitate future treatment decisions and follow ups.展开更多
Objective To investigate the expression of the preferentially expressed antigen of melanoma (PRAME) gene in acute leukemia and its clinical significance. Methods The level of expressed PRAME mRNA in bone marrow mono...Objective To investigate the expression of the preferentially expressed antigen of melanoma (PRAME) gene in acute leukemia and its clinical significance. Methods The level of expressed PRAME mRNA in bone marrow mononuclear cells from 34 patients with acute leukemia (AL) and in 12 bone marrow samples from healthy volunteers was measured via RT-PCR. Correlation analyses between PRAME gene expression and the clinical characteristics (gender, age, white blood count, immunophenotype of leukemia, percentage of blast cells, and karyotype) of the patients were performed. Results The PRAME gene was expressed in 38.2% of all 34 patients, in 40.7% of the patients with acute myelogenous leukemia (AML, n=27), and in 28.6% of the patients with acute lymphoblastic leukemia (ALL, n=7), but was not expressed in the healthy volunteers. The difference in the expression levels between AML and ALL patients was statistically significant. The rate of gene expression was 80% in M~, 33.3% in M2, and 28.6% in M~. Gene expression was also found to be correlated with CDl5 and CD33 expression and abnormal karyotype, but not with age, gender; white blood count or percentage of blast cells. Conclusions The PRAME gene is highly expressed in acute leukemia and could be a useful marker to monitor minimal residual disease. This gene is also a candidate target for the immunotherapy of acute leukemia.展开更多
Objective: The authors used a meta-analytic technique to quantify the evidence of an association between ma- ternal alcohol consumption during pregnancy and childhood acute leukemia (AL), which provided a basis for...Objective: The authors used a meta-analytic technique to quantify the evidence of an association between ma- ternal alcohol consumption during pregnancy and childhood acute leukemia (AL), which provided a basis for the prevention of childhood AL. Methods: Relevant literatures of maternal alcohol consumption during pregnancy were comprehensively searched and screened. Subgroup meta-analysis was conducted according to the type of leukemia. Results of research data of maternal alcohol consumption during pregnancy were tested for heterogeneity. Combined OR values and 95% CIs were statistically calculated with RevMan 4.2 software; Funnel plots were applied to conduct bias analysis for those included litera- tures. Results: Ten related literatures were included after data screening, 4593 cases in AL group and 6157 cases in control group respectively. According to heterogeneity test result (X2 = 16.26, P 〈 0.05), the combined OR values and 95% CI were calculated with random effects model, which were 1.02 (0.92-1.14), Z = 0.41, P = 0.68 〉 0.05, indicating that there was no significant difference between maternal alcohol consumption during pregnancy and the risk of childhood acute leukemia (AL). Subgroup analysis: for the association between maternal alcohol consumption during pregnancy and childhood acute lympho- blastic leukemia (ALL), the combined OR value and 95% CI were 0.92 (0.84-1.00), Z = 1.92, P = 0.05, indicating that there was significant difference between two groups; for the association between maternal alcohol consumption during pregnancy and childhood acute non-lymphoblastic leukemia (ANLL), the combined OR values and 95% CI were 0.82 (0.61-1.11), Z = 1.30, P = 0.19 〉 0.05, indicating that there was no significant difference between two groups. Conclusion: Maternal alcohol consumption during pregnancy is a risk factor in childhood ALL, but not in childhood ANLL.展开更多
A family of coupled map lattice (CML) models has been developed to simulate the evolutional mechanism of interactions of convection, diffusion, and dispersion in both weakly and strongly coupled cases. Not only cohe...A family of coupled map lattice (CML) models has been developed to simulate the evolutional mechanism of interactions of convection, diffusion, and dispersion in both weakly and strongly coupled cases. Not only coherent and turbulent properties as well as their relations, but also the transitional states between convection dominating, diffusion dominating and dispersion dominating are analyzed to demonstrate the essential characteristics of any state. Numerical results show that the models are capable of simulating both layered coupling and stochastic mechanism, and lead us to understand whether or not turbulence coherent structure is formed by modulation of wave packet. The duality of wave and particle characters of turbulence is illustrated in the numerical simulation; a sketch picture is given to explain the questions associated with the turbulent inverse cascade, which is the result of the mutual interactions among the physical factors of nonlinearity, dissipation and dispersion.展开更多
An integrated pest management model of Cost/Benefit analysis strategy was constructed for stem corn borer Sesamia cretica using complementary control measures of different resistant genotypes of corn with the chemical...An integrated pest management model of Cost/Benefit analysis strategy was constructed for stem corn borer Sesamia cretica using complementary control measures of different resistant genotypes of corn with the chemical insecticide diazinon 60%. Based on Cost/Benefit analysis result, the resistant genotype (SAKHA 9433) provides maximum economic value of production at the model point where no spray of insecticide is applied. The applications of one or two sprays do not justify the use of chemical insecticide but rather result in economic loss since the reduction in borer damage value, due to diazinon use, is lower than the cost of control (spray). However, the applications of one spray for the moderate resistant genotype (IPA 2052) and two sprays for the sensitive genotype (CML 323) during corn growing season would be of value to cover the cost of control (spray) but do not achieve similar economic value of revenue comparing with the resistant genotype.展开更多
Abstract:Objective To develop a primary human hematopoietic stem/progenitor cell model for chronic myeloid leukemia (CML) and study signal transduction and molecular regulation mechanisms in CML. Methods We developed ...Abstract:Objective To develop a primary human hematopoietic stem/progenitor cell model for chronic myeloid leukemia (CML) and study signal transduction and molecular regulation mechanisms in CML. Methods We developed a human model of p210BCR/ABL positive CML by transducing normal human umbilical cord blood CD34+ cells with a retroviral vector containing the b3a2 bcr/abl cDNA. We also examined whether this model recreated the cellular phenotype of CML by assessing cell adhesion, cell migration, cell proliferation and cell survival. Results We found that significantly more myeloid colony forming units grew from p210BCR/ABL expressing cells, adhesion of p210BCR/ABL expressing CD34+ cells to fibronectin was decreased but migration over fibronectin was enhanced compared with mock transduced CD34+ cells. In this model, we showed that the presence of p210BCR/ABL leads to elevated levels of p27kip in p210BCR/ABL expressing CD34+ cells. We also showed that multidrug resistance-1 (MDR-1) Pgp was upregulated in the p210BCR/ABL expressing cells which correlates with the expression of p210BCR/ABL. Conclusion This primary human CML model recreates most of the features of CML and provides a useful tool to study signal transduction and downstream molecular regulation drived by the p210BCR/ABL oncogene in normal CD34+ cells.展开更多
Chronic myeloid leukemia(CML) is a form of leukemia characterized by the presence of clonal bone marrow stem cells with the proliferation of mature granulocytes(neutrophils, eosinophils, and basophils) and their precu...Chronic myeloid leukemia(CML) is a form of leukemia characterized by the presence of clonal bone marrow stem cells with the proliferation of mature granulocytes(neutrophils, eosinophils, and basophils) and their precursors. CML is a type of myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia(Ph) chromosome or t(9;22) translocation(BCR-ABL). CML is now usually treated with targeted drugs called tyrosine kinase inhibitors(TKIs). The mechanism and natural history of CML is still unclear. Here, we summarize the present CML animal disease models and compare them with each other. Meanwhile, we propose that it is a very wise choice to establish zebrafish(Danio rerio) CML model mimics clinical CML. This model could be used to learn more about the mechanism of CML, and to aid in the development of new drugs to treat CML.展开更多
Objective: To study the change and role of heme oxygenase-1 (HO-1) in injured lungs following limb ischemia/reperfusion in rats. Methods: A total of 96 healthy male Sprague-Dawley rats, weighing 250-300 g, were used i...Objective: To study the change and role of heme oxygenase-1 (HO-1) in injured lungs following limb ischemia/reperfusion in rats. Methods: A total of 96 healthy male Sprague-Dawley rats, weighing 250-300 g, were used in this study. Hind limb ischemia was made on 40 rats through clamping the infrarenal aorta for 2 hours with a microvascular clip, then limb reperfusion for 0, 4, 8, 16 and 24 hours (n=8 in each time point) was performed, respectively. Other 8 rats undergoing full surgical operation including isolation of the infrarenal aorta without occlusion were taken as the sham operation group. Lung tissues were obtained from the 48 animals and Northern blotting and Western blotting were employed to measure the changes of HO-1 mRNA and protein expression, respectively. Immunohistochemistry technique was used to determine the cell types responsible for HO-1 expression after limb ischemia/reperfusion. Then hind limb ischemia was made on other 12 rats through clamping the infrarenal aorta for 2 hours with a microvascular clip, among whom, 6 rats were given zinc protoporphyrin (ZnPP), an inhibitor of HO. Then limb reperfusion for 16 hours was performed on all the 12 rats. And other 12 rats underwent full surgical operation including isolation of the infrarenal aorta without occlusion, among whom, 6 rats were then given ZnPP. Then lung tissues were obtained from the 24 animals and lung injury markers, lung histology, polymorphonuclear leukocyte (PMN) count and malondialdehyde (MDA) content were detected, respectively. HO activity was determined through measuring the carboxyhemoglobin (COHb) level in artery blood with a CO-oximeter after limb ischemia/reperfusion. And the animal mortality was observed on the other 24 rats. Results: Northern blotting analysis showed that HO-1 mRNA increased significantly at 4 hours after reperfusion, peaked at 16 hours, and began to decrease at 24 hours. In contrast, no positive signal was observed in the sham and simple ischemia animals. Increased HO-1 mRNA levels were accompanied by similar increases in HO-1 protein. Lung PMNs and MDA content increased significantly at 4, 8, 16 and 24 hours after reperfusion, compared with the sham controls (P< 0.001), while they decreased in rats with reperfusion for 16 hours when compared with rats with reperfusion for 4 hours (P< 0.001). Immunohistochemical studies showed that HO-1 was expressed in a variety of cell types, including the airway epithelia, alveolar macrophages and vascular smooth muscular cells. The blood COHb level and animal mortality increased significantly after limb ischemia/reperfusion compared with the sham controls (P< 0.001). ZnPP administrated to the ischemia/reperfusion animals led to a decrease in the COHb level and an increase in lung PMN number, MDA content and animal mortality (P< 0.001 compared with ischemia/reperfusion group), and the lung injury was aggravated. Conclusions: Limb ischemia/reperfusion up-regulates pulmonary HO-1 expression, which serves as a compensatory protective response to the ischemia/reperfusion-induced lung injury in rats.展开更多
OBJECTIVE: To explore the effect of antithymocyte globulin (ATG)/antilymphocyte globulin (ALG) plus kidney-nourishing Chinese medicinal (KNCM) on se- vere aplastic anemia (SAA). METHODS: Twenty-five subjects...OBJECTIVE: To explore the effect of antithymocyte globulin (ATG)/antilymphocyte globulin (ALG) plus kidney-nourishing Chinese medicinal (KNCM) on se- vere aplastic anemia (SAA). METHODS: Twenty-five subjects of severe aplastic anemia were treated with ATG/ALD plus KNCM be- tween 1992 and 2009, and the clinical data before and after treatment were collected and analyzed. RESULTS: Of the 25 patients, 9 were nearly cured, 6 were improved, 5 were in remission, and 5 failed. The overall effective rate was 80.0%. The 3-year, 5-year, 10-year, 15-year survival rate were respec- tively 98.6%, 97.3%, 97.3%, 67.5%, and median sur- vival time was 180 months. Compared to the condi- tions before administering the medication of ATG/ ALG plus KNCM, after 2 weeks, reticulocyte was first improved (P=0.001), one month later, followed by palette (P=0.037), two months later, by neutrophil cell in peripheral blood (P=0.001); three months lat- er, then by the hemoglobin (P=0.012). By conduct- ing 1-year follow-up, 1 case of complication--parox-ysmal nocturnal hemoglobinuria (PNH) was identi- fied and the patient still alive today. CONCLUSION: ATG/ALG fect on SAA and could rate. plus KNCM had better ef- improve patients' survival展开更多
OBJECTIVE:This study screened serum tumor biomarkers by surface enhanced laser desorption/ionization time-of-flight mass spectrometry(SELDI-TOF-MS) to establish a subset which could be used for the prediction of Qi de...OBJECTIVE:This study screened serum tumor biomarkers by surface enhanced laser desorption/ionization time-of-flight mass spectrometry(SELDI-TOF-MS) to establish a subset which could be used for the prediction of Qi deficiency syndrome and phlegm and blood stasis in patients with non-small cell lung cancer;and as diagnostic model of Chinese medicine.METHODS:Serum samples from 63 lung cancer patients with Qi deficiency syndrome and phlegm and blood stasis,and 28 lung cancer patients with non-Qi deficiency syndrome and phlegm and blood stasis were analyzed using SELDI-TOF-MS with a PBS II-C protein chip reader.Protein profiles were generated using immobilized metal affinity capture(IMAC3) protein chips.Differentially-expressed proteins were screened.Protein peak clustering and classification analyses were performed using Biomarker Wizard and Biomarker Pattern software packages,respectively.RESULTS:A total of 268 effective protein peaks were detected in the 1,000-10,000 Da molecular range for the 15 serum proteins screened(P<0.05).The decision tree model was M 2284.97,with a sensitivity of 96.2% and a specificity of 66.7%.CONCLUSION:SELDI-TOF-MS techniques,combined with a decision tree model,can help identify serum proteomic biomarkers related to Qi deficiency syndrome and phlegm and blood stasis in lung cancer patients;and the predictive model can be used to discriminate between Chinese medicine diagnostic models of disease.展开更多
基金Supported by the Namral Science Foundation of Gansu Province,No.ZR-96-078
文摘AIM: To investigate the relationship between serum soluble interleukin-2 receptor (sIL-2R) level and anti-HBc in patients with chronic hepatitis B virus (HBV) infection. METHODS: Sera from 100 patients with chronic HBV infection and 30 healthy controls were included in this study. The patients were divided into group A [HBsAg (+), HBeAg (+) and anti-HBc (+), n = 50] and group B [HBsAg (+), HBeAg (+) and anti-HBc (-), n = 50]. sIL-2R levels were determined using ELISA. HBV DNA and alanine aminotransferase (ALT) were also detected. RESULTS: Serum sIL-2R levels were significantly higher in patients with chronic HBV infection than in healthy controls. Moreover, serum sIL-2R levels were significantly higher in patients with HBsAg (+), HBeAg (+) and antiHBc (+) (976.56±213.51×10^3 U/L) than in patients with HBsAg (+), HBeAg (+) and anti-HBc (-) (393.41±189.54 ×10^3 U/L, P〈 0.01). A significant relationship was found between serum sIL-2R and ALT levels (P〈 0.01) in patients with chronic HBV infection, but there was no correlation between sIL-2R and HBV DNA levels. The anti-HBc status was significantly related to the age of patients (P〈 0.01). CONCLUSION: The high sIL-2R level is related to positive anti-HBc in chronic hepatitis B patients. Positive anti-HBc may be related to T-lymphocyte activation and negative anti-HBc may imply immune tolerance in these patients.
文摘Objective To detect the minimal residual disease in children with B-ALL and to evaluate its clinical significance by flow cytometry. Methods 58 childhood B-ALL cases were enrolled into this study and 33 MRD analyses were performed after remission induction therapy.Four-color combinations of fluorochrome labeled monoclonal antibodies against lymphocyte lineage related phenotypes were used to analyze leukemic cells with flow cytometry.The cells from normal bone marrow were used as controls.The combinations of phenotypes that reflect the antigen expression differences between leukemic and normal bone marrow cells on flow cytometry were considered to be the effective phenotype combinations in the first step screening.The effective phenotype combinations were then used to monitor MRD during the disease course after therapy began. Results 58 cases of childhood B-ALL were screened for MRD effective phenotype combinations.The effective phenotype combinations were identified in 89.7% of B-ALL cases in this study.Four-color phenotype combinations were composed of CD10/CD34/CD19 plus another effective marker such as CD38,CD58,CD66c,CD21.The senstitivity of this method was 0.01%,much higher than that of microscopic inspection.In 8 cases,their bone marrow microscopic inspection results showed no remaining leukemic cells;but with flow cytometry,the percentage of leukemic cells were 5.66%,0.36%,1.43%,0.069%,1.55%,2.7%,0.028% and 0.015%,respectively.In risk stratification,all these MRD positive cases were classified into high risk group for relapse and 1 case showed early relapse within 6 months. Conclusion The application of flow cytometry in MRD measurement can significantly improve the sensitivity of detection of remained leukemic cells in childhood B-ALL,and can provide more accurate information on disease progression as well as the efficacy of therapy,thus facilitate future treatment decisions and follow ups.
文摘Objective To investigate the expression of the preferentially expressed antigen of melanoma (PRAME) gene in acute leukemia and its clinical significance. Methods The level of expressed PRAME mRNA in bone marrow mononuclear cells from 34 patients with acute leukemia (AL) and in 12 bone marrow samples from healthy volunteers was measured via RT-PCR. Correlation analyses between PRAME gene expression and the clinical characteristics (gender, age, white blood count, immunophenotype of leukemia, percentage of blast cells, and karyotype) of the patients were performed. Results The PRAME gene was expressed in 38.2% of all 34 patients, in 40.7% of the patients with acute myelogenous leukemia (AML, n=27), and in 28.6% of the patients with acute lymphoblastic leukemia (ALL, n=7), but was not expressed in the healthy volunteers. The difference in the expression levels between AML and ALL patients was statistically significant. The rate of gene expression was 80% in M~, 33.3% in M2, and 28.6% in M~. Gene expression was also found to be correlated with CDl5 and CD33 expression and abnormal karyotype, but not with age, gender; white blood count or percentage of blast cells. Conclusions The PRAME gene is highly expressed in acute leukemia and could be a useful marker to monitor minimal residual disease. This gene is also a candidate target for the immunotherapy of acute leukemia.
文摘Objective: The authors used a meta-analytic technique to quantify the evidence of an association between ma- ternal alcohol consumption during pregnancy and childhood acute leukemia (AL), which provided a basis for the prevention of childhood AL. Methods: Relevant literatures of maternal alcohol consumption during pregnancy were comprehensively searched and screened. Subgroup meta-analysis was conducted according to the type of leukemia. Results of research data of maternal alcohol consumption during pregnancy were tested for heterogeneity. Combined OR values and 95% CIs were statistically calculated with RevMan 4.2 software; Funnel plots were applied to conduct bias analysis for those included litera- tures. Results: Ten related literatures were included after data screening, 4593 cases in AL group and 6157 cases in control group respectively. According to heterogeneity test result (X2 = 16.26, P 〈 0.05), the combined OR values and 95% CI were calculated with random effects model, which were 1.02 (0.92-1.14), Z = 0.41, P = 0.68 〉 0.05, indicating that there was no significant difference between maternal alcohol consumption during pregnancy and the risk of childhood acute leukemia (AL). Subgroup analysis: for the association between maternal alcohol consumption during pregnancy and childhood acute lympho- blastic leukemia (ALL), the combined OR value and 95% CI were 0.92 (0.84-1.00), Z = 1.92, P = 0.05, indicating that there was significant difference between two groups; for the association between maternal alcohol consumption during pregnancy and childhood acute non-lymphoblastic leukemia (ANLL), the combined OR values and 95% CI were 0.82 (0.61-1.11), Z = 1.30, P = 0.19 〉 0.05, indicating that there was no significant difference between two groups. Conclusion: Maternal alcohol consumption during pregnancy is a risk factor in childhood ALL, but not in childhood ANLL.
基金supported by National Natural Science Foundation of China under Grant No.40535025
文摘A family of coupled map lattice (CML) models has been developed to simulate the evolutional mechanism of interactions of convection, diffusion, and dispersion in both weakly and strongly coupled cases. Not only coherent and turbulent properties as well as their relations, but also the transitional states between convection dominating, diffusion dominating and dispersion dominating are analyzed to demonstrate the essential characteristics of any state. Numerical results show that the models are capable of simulating both layered coupling and stochastic mechanism, and lead us to understand whether or not turbulence coherent structure is formed by modulation of wave packet. The duality of wave and particle characters of turbulence is illustrated in the numerical simulation; a sketch picture is given to explain the questions associated with the turbulent inverse cascade, which is the result of the mutual interactions among the physical factors of nonlinearity, dissipation and dispersion.
文摘An integrated pest management model of Cost/Benefit analysis strategy was constructed for stem corn borer Sesamia cretica using complementary control measures of different resistant genotypes of corn with the chemical insecticide diazinon 60%. Based on Cost/Benefit analysis result, the resistant genotype (SAKHA 9433) provides maximum economic value of production at the model point where no spray of insecticide is applied. The applications of one or two sprays do not justify the use of chemical insecticide but rather result in economic loss since the reduction in borer damage value, due to diazinon use, is lower than the cost of control (spray). However, the applications of one spray for the moderate resistant genotype (IPA 2052) and two sprays for the sensitive genotype (CML 323) during corn growing season would be of value to cover the cost of control (spray) but do not achieve similar economic value of revenue comparing with the resistant genotype.
基金ThisstudywassupportedbyTianjinKeyProjectFund grant 99380 45 11
文摘Abstract:Objective To develop a primary human hematopoietic stem/progenitor cell model for chronic myeloid leukemia (CML) and study signal transduction and molecular regulation mechanisms in CML. Methods We developed a human model of p210BCR/ABL positive CML by transducing normal human umbilical cord blood CD34+ cells with a retroviral vector containing the b3a2 bcr/abl cDNA. We also examined whether this model recreated the cellular phenotype of CML by assessing cell adhesion, cell migration, cell proliferation and cell survival. Results We found that significantly more myeloid colony forming units grew from p210BCR/ABL expressing cells, adhesion of p210BCR/ABL expressing CD34+ cells to fibronectin was decreased but migration over fibronectin was enhanced compared with mock transduced CD34+ cells. In this model, we showed that the presence of p210BCR/ABL leads to elevated levels of p27kip in p210BCR/ABL expressing CD34+ cells. We also showed that multidrug resistance-1 (MDR-1) Pgp was upregulated in the p210BCR/ABL expressing cells which correlates with the expression of p210BCR/ABL. Conclusion This primary human CML model recreates most of the features of CML and provides a useful tool to study signal transduction and downstream molecular regulation drived by the p210BCR/ABL oncogene in normal CD34+ cells.
基金supported by National Natural Science Foundation of China (81270631)the National Natural Science Foundation of China for Overseas ChineseHong Kong and Macao Scholars Collaborated Researching Fund(31229003)
文摘Chronic myeloid leukemia(CML) is a form of leukemia characterized by the presence of clonal bone marrow stem cells with the proliferation of mature granulocytes(neutrophils, eosinophils, and basophils) and their precursors. CML is a type of myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia(Ph) chromosome or t(9;22) translocation(BCR-ABL). CML is now usually treated with targeted drugs called tyrosine kinase inhibitors(TKIs). The mechanism and natural history of CML is still unclear. Here, we summarize the present CML animal disease models and compare them with each other. Meanwhile, we propose that it is a very wise choice to establish zebrafish(Danio rerio) CML model mimics clinical CML. This model could be used to learn more about the mechanism of CML, and to aid in the development of new drugs to treat CML.
基金ThisworkwassupportedbytheNationalNaturalScienceFoundationofChina (No .30 2 71337)
文摘Objective: To study the change and role of heme oxygenase-1 (HO-1) in injured lungs following limb ischemia/reperfusion in rats. Methods: A total of 96 healthy male Sprague-Dawley rats, weighing 250-300 g, were used in this study. Hind limb ischemia was made on 40 rats through clamping the infrarenal aorta for 2 hours with a microvascular clip, then limb reperfusion for 0, 4, 8, 16 and 24 hours (n=8 in each time point) was performed, respectively. Other 8 rats undergoing full surgical operation including isolation of the infrarenal aorta without occlusion were taken as the sham operation group. Lung tissues were obtained from the 48 animals and Northern blotting and Western blotting were employed to measure the changes of HO-1 mRNA and protein expression, respectively. Immunohistochemistry technique was used to determine the cell types responsible for HO-1 expression after limb ischemia/reperfusion. Then hind limb ischemia was made on other 12 rats through clamping the infrarenal aorta for 2 hours with a microvascular clip, among whom, 6 rats were given zinc protoporphyrin (ZnPP), an inhibitor of HO. Then limb reperfusion for 16 hours was performed on all the 12 rats. And other 12 rats underwent full surgical operation including isolation of the infrarenal aorta without occlusion, among whom, 6 rats were then given ZnPP. Then lung tissues were obtained from the 24 animals and lung injury markers, lung histology, polymorphonuclear leukocyte (PMN) count and malondialdehyde (MDA) content were detected, respectively. HO activity was determined through measuring the carboxyhemoglobin (COHb) level in artery blood with a CO-oximeter after limb ischemia/reperfusion. And the animal mortality was observed on the other 24 rats. Results: Northern blotting analysis showed that HO-1 mRNA increased significantly at 4 hours after reperfusion, peaked at 16 hours, and began to decrease at 24 hours. In contrast, no positive signal was observed in the sham and simple ischemia animals. Increased HO-1 mRNA levels were accompanied by similar increases in HO-1 protein. Lung PMNs and MDA content increased significantly at 4, 8, 16 and 24 hours after reperfusion, compared with the sham controls (P< 0.001), while they decreased in rats with reperfusion for 16 hours when compared with rats with reperfusion for 4 hours (P< 0.001). Immunohistochemical studies showed that HO-1 was expressed in a variety of cell types, including the airway epithelia, alveolar macrophages and vascular smooth muscular cells. The blood COHb level and animal mortality increased significantly after limb ischemia/reperfusion compared with the sham controls (P< 0.001). ZnPP administrated to the ischemia/reperfusion animals led to a decrease in the COHb level and an increase in lung PMN number, MDA content and animal mortality (P< 0.001 compared with ischemia/reperfusion group), and the lung injury was aggravated. Conclusions: Limb ischemia/reperfusion up-regulates pulmonary HO-1 expression, which serves as a compensatory protective response to the ischemia/reperfusion-induced lung injury in rats.
文摘OBJECTIVE: To explore the effect of antithymocyte globulin (ATG)/antilymphocyte globulin (ALG) plus kidney-nourishing Chinese medicinal (KNCM) on se- vere aplastic anemia (SAA). METHODS: Twenty-five subjects of severe aplastic anemia were treated with ATG/ALD plus KNCM be- tween 1992 and 2009, and the clinical data before and after treatment were collected and analyzed. RESULTS: Of the 25 patients, 9 were nearly cured, 6 were improved, 5 were in remission, and 5 failed. The overall effective rate was 80.0%. The 3-year, 5-year, 10-year, 15-year survival rate were respec- tively 98.6%, 97.3%, 97.3%, 67.5%, and median sur- vival time was 180 months. Compared to the condi- tions before administering the medication of ATG/ ALG plus KNCM, after 2 weeks, reticulocyte was first improved (P=0.001), one month later, followed by palette (P=0.037), two months later, by neutrophil cell in peripheral blood (P=0.001); three months lat- er, then by the hemoglobin (P=0.012). By conduct- ing 1-year follow-up, 1 case of complication--parox-ysmal nocturnal hemoglobinuria (PNH) was identi- fied and the patient still alive today. CONCLUSION: ATG/ALG fect on SAA and could rate. plus KNCM had better ef- improve patients' survival
基金Supported by the National Natural Science Foundation of China(No.30572293)the "Eleventh Five" TCM Foundation for Major Clinical Research of PLA(No.2006051002)the Natural Science Foundation of Fujian Province,China(No. 2010J01197)
文摘OBJECTIVE:This study screened serum tumor biomarkers by surface enhanced laser desorption/ionization time-of-flight mass spectrometry(SELDI-TOF-MS) to establish a subset which could be used for the prediction of Qi deficiency syndrome and phlegm and blood stasis in patients with non-small cell lung cancer;and as diagnostic model of Chinese medicine.METHODS:Serum samples from 63 lung cancer patients with Qi deficiency syndrome and phlegm and blood stasis,and 28 lung cancer patients with non-Qi deficiency syndrome and phlegm and blood stasis were analyzed using SELDI-TOF-MS with a PBS II-C protein chip reader.Protein profiles were generated using immobilized metal affinity capture(IMAC3) protein chips.Differentially-expressed proteins were screened.Protein peak clustering and classification analyses were performed using Biomarker Wizard and Biomarker Pattern software packages,respectively.RESULTS:A total of 268 effective protein peaks were detected in the 1,000-10,000 Da molecular range for the 15 serum proteins screened(P<0.05).The decision tree model was M 2284.97,with a sensitivity of 96.2% and a specificity of 66.7%.CONCLUSION:SELDI-TOF-MS techniques,combined with a decision tree model,can help identify serum proteomic biomarkers related to Qi deficiency syndrome and phlegm and blood stasis in lung cancer patients;and the predictive model can be used to discriminate between Chinese medicine diagnostic models of disease.