86 results on '"Fang, Jian-Pei"'
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2. Influence of Blocking B7/CD28 and CD40/CD154 Co-stimulatory Signals on Immune Function of Sensitized Mice.
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YE Qi-Xiang, XU Lu-Hong, XU Wei, and FANG Jian-Pei
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- 2014
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3. Comparison of the Anti-Leukemia Effect and Mechanism of L-Asparaginase between Two Different Strains.
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WANG Kai-Mei, XU Hong-Gui, GUO Hai-Xia, JIN Shao-Wen, LUO Xiang-Qin, and FANG Jian-Pei
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- 2014
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4. Effects of CD4+ CD25+ Regulatory T Cells on Allogeneic Hematopoietic Stem Cell Transplantation in Sensitized Mice.
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YE Qi-Xiang, WENG Wen-Jun, XU Lu-Hong, and FANG Jian-Pei
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- 2014
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5. Relation of Treg and iNKT Cell Reconstruction with aGVHD after Allogenetic Hematopoietic Stem Cell Transplantation in Chidren.
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WANG Peng-Fei, HUANG Ke, FANG Jian-Pei, ZHOU Dun-Hua, GUO Hai-Xia, CHEN Yan-Yan, CHEN Chun, and LI Yang
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- 2014
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6. Effects of Blocking Co-stimulatory Signals on Immunotolerance Rejection of Sensitized Recipient after Hematopoietic Stem Cell Transplantation.
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YE Qi-Xiang, WENG Wen-Jun, XU LYu-Hong, and FANG Jian-Pei
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- 2014
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7. In Vitro Amplification of CD4+ CD25+ Regulatory T Cells and Identification of Amplified T Cell Immunoinhibitory Function.
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WENG Wen-Jun, PAN Li, FANG Jian-Pei, and XU Lŭ-Hong
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- 2013
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8. Therapeutic Efficacy Evaluation of Rabbit Anti-thymocyte Globulin Combined with Cyclosporine A in Children with Aplastic Anemia.
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FU Ru-Ting, XUE Hong-Man, XU Hong-Gui, Huang Ke, FANG Jian-Pei, HUANG Shao-Liang, and CHEN Chun
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- 2013
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9. Analysis of One Case of Adolescent Blastic Plasmacytoid Dendritic Cell Neoplasm.
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MA Lei, LI Yang, LIU Ling, GUO Hai-Xia, XUE Hong-Man, LIN Su-Xia, XU Hong-Gui, HUANG Shao-Liang, CHEN Chun, and FANG Jian-Pei
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- 2013
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10. Separation and Amplification of CD4+ CD25+ Regulatory T Cells from Sensitized Mice.
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Pan Li, Weng Wen-Jun, Xu Lü-Hong, Wei Jing, and Fang Jian-Pei
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- 2012
11. Effect of Thalassemia Panel Reactive Antibody on Proliferation and Apoptosis of Cord Blood CD34+ Cells.
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Yang Xing-Ge, Lu Xue-Liang, Xu Lii-Hong, and Fang Jian-Pei
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- 2012
12. Culture In Vitro and Lentivirus Transection of Rat Mesenchymal Stem Cells.
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Zhang Hong-Shan, Fang Jian-Pei, Su Hao-Bin, and Yang Min
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- 2011
13. Effects of Mesenchymal Stem Cells on Lymphocyte Proliferation of sensitized Mice In Vitro and Ineir Action Manner.
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Hong Dong-Ling, Wu Yan-Fang, Xu Lü-Hong, and Fang Jian-Pei
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- 2011
14. Therapeutic Effect of Focal Adhesion Kinase Gene Silence on Leukema.
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XU Lü-Hong, FANG Jian-Pei, WENG Wen-Jun, XU Hong-Gui, and ZHANG Ya-Ting
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- 2011
15. Transfusion of Hematopoietic Stem/Progenitor Cells into Marrow Cavity in Sensitized Mouse Model.
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XU Lü-Hong, FANG Jian-Pei, WENG Wen-Jun, and SHI Pei-Jie
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- 2011
16. Influence of FcγRIIIa Polymorphism on Rituximab-dependent NK Cell-mediated Cytotoxicity to Raji Cells.
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QU Yu-Hua, LI Yang, WU Yan-Feng, FANG Jian-Pei, HUANG Shao-Liang, HUANG Yan, and WEI Jing
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- 2010
17. Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia by Using Real-time Quantitative PCR.
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ZHANG Ya-Ting, LUO Zhao-Fan, FANG Jian-Pei, GUO Hai-Xia, HUANG Ke, and LI Chi-Kong
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- 2010
18. FCγ Receptor III a Polymorphism in Healthy Children and Those with Hematological Malignancies.
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QU Yu-Hua, LI Yang, WU Yan-Feng, FANG Jian-Pei, WEI Jing, HUANG Shao-Liang, MA Xiao-Xiao, and HUANG Yan
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- 2010
19. Construction of pcDNA3.1 ( + )/A2E Eukaryotic Expression Vector and Its Expression on K562 cell.
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LIU Si-Xi, FANG Jian-Pei, XU Hong-Gui, CHEN Guo-Hua, and HUANG Shao-Liang
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- 2005
20. Analysis on HLA-E Polymorphism in Guangdong Han Population.
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ZHEN Zi-Jun, FANG Jian-Pei, DENG Qing-Li, XU Hong-Gui, FAN Li-An, and HUANG Shao-Liang
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- 2004
21. Establishment of a Murine Model for Allogeneic Umbilical Cord Blood Transplantation.
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HUANG Shao-Liang, HUANG Wen-Ge, XU Hong-Gui, FANG Jian-Pei, WEI Jing, CHEN Feng-Ying, GUO Fen-Fen, and LI Shu-Nong
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- 2002
22. Clinical Study on A Patient with Intestinal Acute Graft-Versus-Host Disease Grade IV after Allo-Peripheral Blood Stem Cell Transplantation.
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CHEN Chun, FANG Jian-Pei, HUANG Shao-Liang, BAO Rong, and WU Yan-Fong
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- 2001
23. Association of the Relationship between HLA-DQB1 * Alleles and Major β-Thalassemia in 42 Guangdong Chinese.
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BAO Rong, CHEN Chun, FANG Jian-Pei, and HUANG Shao-Liang
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- 2002
24. [Relationship between MTHFR Gene Polymorphism(C677T) and Adverse Reactions of High-Dose Methotrexate in Pediatric Patients with Acute Lymphoblastic Leukemia].
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Yang FY, Xu LH, Wang J, Zhang YT, Lin SF, Wang KM, Zhou DH, and Fang JP
- Abstract
Objective: To explore the effects of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism on the adverse reactions of high-dose methotrexate (MTX) in pediatric patients with acute lymphoblastic leukemia (ALL)., Methods: A total of 69 children with ALL admitted to the department of Pediatrics of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from November 2018 to October 2020 were included in this study. The clinical data of the children were collected, leukocytes were isolated from their peripheral blood, and MTHFR genotyping was performed by digital fluorescence molecular hybridization techniques. The adverse reactions and plasma drug concentration of MTX were monitored during the chemotherapy. Moreover, the effect of MTHFR gene polymorphism on MTX adverse reactions and plasma drug concentration were analyzed., Results: Among the middle and high risk children, compared with the wildtype group (CC genotype), patients with MTHFR C677T mutations (CT+TT genotypes) had a higher risk of leukopenia ( OR =2.38), neutropenia ( OR =2.2), anemia ( OR =1.83) and hepatoxicity ( OR =1.98). However, no significant difference was found in the MTX plasma concentration between the MTHFR C677T mutantion group and the wildtype group at different timepoints (24 h, 48 h and 72 h). Multivariate analysis revealed that the plasma concentration of MTX (48 h), clinical risk level of ALL and MTHFR C677T gene polymorphism were independent factors for the adverse reactions of high-dose MTX., Conclusion: The MTHFR C677T mutations may be associated with myelosuppression and hepatotoxicity in children with ALL after high-dose MTX treatment.
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- 2023
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25. [Clinical Analysis of Pediatric Acute Leukemia Complicated with Septic Shock].
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Liu TH, Lei JY, Mai YG, and Fang JP
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- Humans, Child, Adolescent, Retrospective Studies, ROC Curve, Shock, Septic complications, Leukemia, Heart Failure
- Abstract
Objective: To analyze the clinical characteristics of predictors in pediatric acute leukemia complicated with septic shock and explore the prognostic factors., Methods: The clinical characteristics of 70 children with acute leukemia and complicated with septic shock hospitalized in Sun Yat-sen Memorial Hospital from March 2012 to March 2021 were retrospectively analyzed. The clinical characteristics of patients in survival group and death group were analyzed and compared. Multiple logistic regression was used to test for predictors of death., Results: Among the 70 children, 41 were males and 29 were females, with a median age of 7.0 (1.0-15.0) years old. 81.4% were hospital acquired infections. The pathogens were mostly Gram-negative bacteria (50/66, 75.8%) and the clinical manifestations were cold shock. Mortality rate was 34.3% (24/70). The length of hospitalization, duration of fever and antibiotic exposure longevity before the onset of septic shock were significantly different between survival group and death group. At septic shock onset, compared with the survival group, patients in the death group were younger, had lower platelet counts and higher levels of C-reactive protein and procalcitonin, and were more likely to have acute heart failure and more mechanical ventilation (all p <0.05). The results of multivariable analysis showed that mortality was independently associated with pediatric sequential organ failure assessment score (pSOFA) (odds ratio: 1.616, 95% CI : 1.160-2.251, p =0.005) and acute heart failure (odds ratio: 18.308, 95% CI : 1.939-172.911, p =0.011). In addition, the ROC curve analysis showed that pSOFA score had AUC of 0.8551 (95% CI : 0.7607-0.9495, p <0.001) predicting PICU mortality and its best predictive value was >9.5 (sensitivity 75.0%, specificity 87.0%)., Conclusion: Pediatric acute leukemia complicated with septic shock is characterized as rapid deterioration and high mortality. A pSOFA score greater than 9.5 and acute heart failure are associated with poor outcomes.
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- 2022
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26. [Clinical Characteristic, Diagnosis and Treatment of Acute Lymphoblastic Leukemia Combined with Pneumocystis Carinii Pneumonia in Children].
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Lin SF, Hou LL, Wang J, Xu LH, Liu Y, Mai YG, Fang JP, and Zhou DH
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- Caspofungin therapeutic use, Child, Child, Preschool, Dyspnea, Female, Humans, Male, Respiratory Sounds, Retrospective Studies, Pneumonia, Pneumocystis diagnosis, Pneumonia, Pneumocystis therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Objective: To investigate the clinical characteristics and treatment of pneumocystis carinii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL), in order to improve the early diagnosis and effective treatment., Methods: Clinical data of five children with ALL developing PCP in the post-chemotherapy granulocyte deficiency phase were analyzed retrospectively. The clinical manifestations, laboratory tests, imaging findings, treatment methods and effect were summarized., Results: The male-to-female ratio of the five children was 1∶4, and the median age was 5.5 (2.9-8) years old. All patients developed PCP during granulocyte deficiency phase after induction remission chemotherapy. The clinical manifestations were generally non-specific, including high fever, tachypnea, dyspnea, non-severe cough, and rare rales in two lungs (wet rales in two patients). Laboratory tests showed elevated C-reactive protein (CRP), serum procalcitonin (PCT), (1,3)-β-D-glucan (BDG), lactate dehydrogenase (LDH) and inflammatory factors including IL-2R, IL-6 and IL-8. Chest CT showed diffuse bilateral infiltrates with patchy hyperdense shadows. Pneumocystis carinii(PC) was detected in bronchoalveolar lavage fluid (BALF) or induced sputum by high-throughput sequencing in all patients. When PCP was suspected, chemotherapy was discontinued immediately, treatment of trimethoprim-sulfame thoxazole (TMP-SMX) combined with caspofungin against PC was started, and adjunctive methylprednisolone was used. Meanwhile, granulocyte-stimulating factor and gammaglobulin were given as the supportive treatment. All patients were transferred to PICU receiving mechanical ventilation due to respiratory distress during treatment. Four children were cured and one died., Conclusion: PCP should be highly suspected in ALL children with high fever, dyspnea, increased LDH and BDG, and diffuse patchy hyperdense shadow or solid changes in lung CT. The pathogen detection of respiratory specimens should be improved as soon as possible. TMP/SMZ is the first-line drug against PCP, and the combination of Caspofungin and TMP/SMZ treatment for NH-PCP may have a better efficacy. Patients with moderate and severe NH-PCP may benefit from glucocorticoid.
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- 2022
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27. [Efficacy of Posaconazole for Primary Prophylaxis in the Induction Therapy of Childhood Acute Lymphoblastic Leukemia].
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Zhang YT, Wang J, Zhou DH, and Fang JP
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- Antifungal Agents therapeutic use, Child, Humans, Induction Chemotherapy, Primary Prevention, Triazoles, Mycoses drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Objective: To explore the effect of posaconazole in the primary prevention of invasive fungal disease (IFD) in the induction therapy of childhood acute lymphoblastic leukemia (ALL)., Methods: From August 2018 to November 2020, 144 pediatric patients with ALL treated in Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University were selected, 88 cases received fluconazole as IFD prophylaxis (fluconazole prophylaxis group), 56 cases received posaconazole as IFD prophylaxis (posaconazole prophylaxis group). The incidence of IFD and treatment-related adverse reactions between the two groups were compared, and the safety of posaconazole was evaluated., Results: The incidence of IFD in the fluconazole prophylaxis group was 20.4% (18/88), and in the posaconazole prophylaxis group was 7.1% (4/56). The incidence of IFD between the two groups was statistically significant different(P=0.030). There was no serious adverse reactions in the two groups. The incidence of mild adverse reactions in the posaconazole prophylaxis group (23.2%) was lower than that in the fluconazole prophylaxis group(39.8%), and the difference was statistically significant (P=0.039). There were 12 cases died in the fluconazole prophylaxis group and 4 in the posaconazole prophylaxis group, while no significant difference in the overall survival rate between the two groups (P=0.281)., Conclusion: The effect of posaconazole in the primary prophylaxis of IFD is better and incidence of adverse reactions is lower than fluconazole. Posaconazole can be tolerated, and expected to become the first-line primary prophylaxis drug for IFD during the induction remission therapy of childhood ALL.
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- 2021
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28. [Prevalence Rate and Risk Factors of Hypothyroidism in Children with Beta Thalassemia Major in Zhuhai Area].
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Chen M, Duan L, Zhou CX, and Fang JP
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- Child, Humans, Prevalence, Risk Factors, Hypothyroidism epidemiology, Iron Overload, beta-Thalassemia epidemiology
- Abstract
Objective: To investigate the prevalence rate of hypothyroidism in children with β-thalassemia major (β-TM) and its risk factors., Methods: A total of 86 children with β-TM treated and followed up in the Department of Pediatrics of the Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai Municipal Maternal and Child Health Care Hospital from August 2018 to August 2020 were enrolled. The clinical data of the children were analyzed to investigate the prevalence rate of hypothyroidism in children with β-thalassemia major (β-TM) and its risk factors., Results: The prevalence rate of hypothyroidism in children with β-TM in Zhuhai area was 17.4%. The level of serum ferritin(SF) (4948.27±1225.33 μg/L) in hypothyroidism children was significantly increased(t=10.273,P<0.05). The prevalence rate of hypothyroidism was significantly higher in β-TM children(age ≥10 years old, SF ≥2 500 μg/L and irregular iron removal) (P<0.05). Logistic regression result showed that age ≥10 years old was the independent risk factor affecting the increasing of hypothyroidism rate in the children. The levels of SF(3880.60±1269.17 μg/L), TSH(4.43±1.52 mIU/L) and the prevalence rate of hypothyroidism(37.14%)(P<0.05) were higher for the children in irregular iron removal group., Conclusion: The prevalence rate of hypothyroidism in children with β-TM in Zhuhai area is high, and it is related to the age ≥10 years old, SF ≥2 500 μg/L and irregular iron removal of the children.
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- 2021
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29. [Research Progress on Gene Therapy for β-thalassemia---Review].
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Hong WC, Fang JP, and Xu LH
- Subjects
- Gene Editing, Genetic Therapy, Genetic Vectors, Humans, beta-Globins genetics, beta-Thalassemia genetics, beta-Thalassemia therapy
- Abstract
β-thalassemia is a monogenetic inherited hemolytic anemia, which results in a series of pathophysiological changes due to partial or complete inhibition of the synthesis of β-globin chain. The curative therapy for this disease is to reconstitute hematopoiesis, and transplantation with genetically modified autologous hematopoietic stem cells can avoid the major difficulties of traditional allogeneic hematopoietic stem cell transplantation,such as HLA matching and immune rejection. β-thalassemia gene therapy strategies mainly include gene integration and genome editing. The former relies on the development of lentiviral vectors and adds a fully functional HBB gene to the chromosome; the latter rapidly develops with the research of specific nuclease which can repair the HBB gene in situ. In this review, the latest progress of the two strategies in gene therapy of β-thalassemia is summarized.
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- 2021
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30. [Analysis of Clinical Characteristics and Prognosis in Children with Acute Megakaryoblastic Leukemia without Down Syndrome].
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Lin SF, Guo SY, Liu S, Wang J, Huang K, Li Y, Fang JP, and Zhou DH
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- Child, Child, Preschool, DEAD-box RNA Helicases, DNA Helicases, Female, Humans, Male, Prognosis, Retrospective Studies, Trisomy, Down Syndrome, Leukemia, Megakaryoblastic, Acute genetics
- Abstract
Objective: To analyze the clinical characteristics and treatment effects of children with acute megakaryoblastic leukemia without down syndrome (non-DS-AMKL)., Methods: The clinical data of 19 children with non-DS-AMKL treated in the Pediatric Hematology Ward in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from May 2008 to April 2018 were analyzed retrospectively. The clinical characteristics, laboratory test and treatment methods of the children were concluded. All patients were followed up to evaluate the effect of treatment., Results: The 19 cases of children included nine male and ten female, the median age of onset was 2 years old. The clinical manifestations showed nonspecific. The median white blood cell of peripheral blood was 15.88×10
9 /L, the median hemoglobin was 67 g/L and median platelet was 16×109 /L. An increase of primitive and naive megakaryocytes was found in the bone marrow sample. The immunophenotypes of bone marrow detected by flow cytometry in 19 children were all positive expressed for CD41, CD61. Genetic tests showed that five cases carrying EVI1, including one complicating with MLL/AF10, one patient carrying HOX11, one carrying GATA1, IKZF1 and DDX11 mutations, one patient carrying missense mutation of NRAS, one with missense mutation of KRAS and two cases with high expression of WT1. Karyotype analysis were performed in 11 cases of children, including four with normal karyotype, four with complex karyotypes, one with trisomy 8, one with 7/13 trisomy 21 without Down syndrome manifestations (considered as abnormal somatic karyotype) and one Robertsonian translocation carrier involving chromosomes 14 and 21. Ten children received treatment, including three cases with allogeneic hematopoietic stem cell transplantation (allo-HSCT) after complete remission (CR), two cases with complete donor implantation, and one without implanted but hematopoietic recovered, these three children were followed up for 26, 15 and 12 months respectively and the minimal residual disease (MRD) were all less than 10-4 . Another three cases achieving CR after chemotherapy but relapsed in 5, 10 and 12 months after the onset respectively, and all the three children were died eventually. One children died of pulmonary hemorrhage during chemotherapy and three children died from discontinuation of treatment after non remission. The remaining nine children died because of without chemotherapy treatment., Conclusion: Non-DS-AMKL was rare in children and difficult to be diagnosed. Determination of MICM classification as early as possible was helpful for diagnosis, and genetic testing played an important role for diagnosis and prognosis evaluation. Early hematopoietic stem cell transplantation in patients with CR after chemotherapy might be an effective way to cure AMKL.- Published
- 2021
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31. [Values of MCV,MCH,ROFT and HbA 2 for Screening α-Thalassemia in Guangdong Area].
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Liu Y, Lin XY, Huang Y, Huang QW, Chen HL, Shen MN, Ruan JY, Li XY, Xu LH, and Fang JP
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- Hemoglobin A2 analysis, Humans, Mass Screening, Sensitivity and Specificity, Erythrocyte Indices, alpha-Thalassemia diagnosis, alpha-Thalassemia genetics
- Abstract
Objective: To investigate the values of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), red cell osmotic fragility test(ROFT) and hemoglobin A2(HbA
2 ) in screening of α-thalassemia in Guangdong area., Methods: A total of 285 peripheral blood samples in patients treated in our hospital from January 2017 to December 2017 were collected. The detection of thalassemia gene was used as the gold standard, while blood routine examination, hemoglobin electrophoresis, and red cell osmotic fragility test were simultaneously performed. The optimal cut-off values in MCV, MCH, ROFT and HbA2 in α-thalassemia were determined by receiver operator characteristic curve (ROC curve)., Results: The most common types of α-thalassemia gene was --SEA/αα (54.59%). Compared with the control group, the differences in MCV, MCH, ROFT and HbA2 showed statistically significantce between different types of α-thalassemia (P<0.05). The best cut-off values of MCV, MCH, ROFT, and HbA2 in the diagnosis of α-thalassemia were 81.45 fl, 27.35 pg, 79.95%, and 2.55% respectively., Conclusion: For different laboratories, the cut-off values need to be established for screening α-thalassemia suitable in their own local region.The values of MCV, MCH, ROFT and HbA2 shows higher accuracy and sensitivity in the diagnosis of α-thalassemia. It is recommended to use MCV<81.45fl, MCH<27.35 pg, ROFT<79.95% and HbA2 <2.55% as the standards for screening α-thalassemia in Guangdong area.- Published
- 2020
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32. [Knockdown of ALAS2 Affects Erythroid Differentiation by Down-regulating Mitophagy Receptor BNIP3L].
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Hu ST, Li XY, Chen H, Xu LH, and Fang JP
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- 5-Aminolevulinate Synthetase metabolism, Apoptosis, Cell Differentiation, Humans, K562 Cells, Membrane Proteins genetics, Membrane Proteins metabolism, Proto-Oncogene Proteins genetics, Tumor Suppressor Proteins, Carrier Proteins, Mitophagy
- Abstract
AbstractObjective: To investigate the effect of ALAS2 downregulation on the expression of BNIP3L and erythroid differentiation in K562 cells., Methods: The expression of ALAS2 was down-regulated by transfection of lentivirus, then quantitative real-time PCR was performed to detect the transfection efficiency. Flow cytometry analysis was applied to evaluate apoptosis of cells, erythroid differentiation, mitochondrial membrane potential and reactive oxygen species (ROS) level. Western blot was used to detect the BNIP3L expression, Co-immunoprecipitation was performed to analyze the relationship between ALAS2 and BNIP3L., Results: Compared with sh-NC group, knockdown of ALAS2 induced downregulation of BNIP3L mRNA and protein expression(P<0.01) and erythroid related transcription factors GATA1, Nrf2 expression, as well as reduction of ROS level(P<0.05). Mitochondrial membrane potential of control (sh-NC) group was lower than that of shALAS2 group(P<0.05), but there was no significant change of cell apoptotic rate in two groups. CD71highCD235ahigh + CD71lowCD235ahigh cells of sh-NC and shALAS2 groups were 53.5%, 92.9% at 96 h after hemin induction, respectively. No direct action between ALAS2 and BNIP3L was observed., Conclusion: The intracellular heme level can affect the expression of BNIP3L which may be related with the regulation of ROS and transcription factors GATA1 and Nrf2. Higher BNIP3L facilitates cell differentiation but lower BNIP3L is favorable for cells survival.
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- 2020
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33. [Preliminary Study of Chidamide Combined with Hematopoietic Stem Cell Transplantation in the Treatment of Childhood Acute T-Lymphoblastic Leukemia].
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Zhang YT, Huang K, Xu LH, Han XW, Li XY, and Fang JP
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- Aminopyridines, Benzamides, Child, Humans, Recurrence, Transplantation, Homologous, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Abstract
Objective: To investigate the efficacy and safety of combination chidamide and hematopoietic stem cell transplantation (HSCT) in the treatment of childhood acute T lymphoblastic leukemia (T-ALL)., Methods: Seven children with acute T lymphoblastic leukemia received hematopoietic stem cell transplantation in SUN Yat-Sen Memorial Hospital of SUN Yat-Sen University were selected. 7 cases of T-ALL were divided into 2 groups: HSCT plus chidamide-treated group (4 cases) and traditional HSCT-treated group (3 cases) as control. The incidence of GVHD and other related complications, as well as implantation, recurrence and survival were compared between the two groups, and the side effects of chidamide were observed. All the patients were follow-up until January 2019., Results: All the 7 patients were alive and, there was no difference in the incidence of acute GVHD between the HSCT plus chidamides treated group and the traditional HSCT-treated group. The implantation rate of HSCT was 100%, and there were no recurrence occurred. During the application of chidamide, 3 cases showed adverse reactions, of which 2 cases had adverse reactions of grade 3 or higher, and 2 cases were hematological adverse reactions (neutropenia, thrombocytopenia), other adverse reactions were non-hematologic adverse reactions (transaminase elevation, fatigue, nausea, vomiting), there were no serious adverse reactions occurred. In the HSCT plus chidamide-treated group, 2 cases were found that mature lymphocytes were not expressed by tumors, during examing for minimal redidaul disease (MRD). Compared with the immunophenotype and TCR rearrangement at first diagnosis, the results did not support the source of residual T-ALL tumor cells. During the review of MRD, it was found that the abnormal T cells showed an increasing trend, indicating that chidamide might induce leukemia cell differentiation through some pathways., Conclusion: Hematopoietic stem cell transplantation is still an effective method to cure children's T-ALL. In some cases, abnormal T-cell nonclonal amplification occurs during the application of chidamide, and the children with T-ALL can tolerable adverse reactions of chidamide.
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- 2020
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34. [Efficacy of BMMSCs on aGVHD and Its Correlation with SerumInflammatory Cytokines in Pediatric Patients with Severe Refractory Acute Graft-Versus-Host Disease].
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Guo SY, Qiu KY, Tang XK, Huang K, Xu HG, Li Y, Weng WJ, Xu LH, Fang JP, and Zhou DH
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- Acute Disease, Child, Cytokines, Humans, Transplantation, Homologous, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Mesenchymal Stem Cells
- Abstract
Objective: To investigate the efficacy of bone marrow mesenchymal stem cells (BMMSC) on children with refractory graft-versus-host disease (GVHD) and to judge the efficacy of BMMSC by dynamically monitoring the changes of cytokines in children with GVHD before and after infusion of BMMSC, so as to provide a theoretical basis for clarifying the mechanism of BMMSC., Methods: 17 children with refractory aGVHD including 7 of grade II, 6 cases of grade III and 4 cases of grade IV after allo-HSCT were enrolled. All the children with aGVHD, who received routine immunosuppressive therapy, but the state of disease not improved, were treated with immunosuppressive drugs combined with BMMSC infusion. Study endpoints included safety of BMMSC infusion, response to BMMSC, and overall response of aGVHD. The serum levels of IL-2α, IL-6, IL-10, IL-8 and TNF-α in aGVHD patients were measured by chemiluminescence before infusion of BMMSCs and Day 7, Day 14 after infusion of BMMSCs., Results: The cumulative median dose of BMMSCs was 5.5 (3.4-11.1) × 10
6 /kg for average of 3.7 times, and the median time of 16.5 (4-95) days for the first infusion of MSCs. In 17 cases of refractory GVHD, 14 responded to treatment, whereas 3 patients failed. The total effective rate was 82.4% and no adverse reactions occurred. Of the 14 survived cases (82.4%), the median follow-up time was 944 (559-1245) days from the first infusion of MSCs. The levels of TNF-α in children with grade II, III and IV GVHD before treatment were 9.5±4.3 pg/ml, 16.3±10.9 pg/ml and 35.8±21.2 pg/ml respectively. The difference between grade II and IV, III and IV was statistically significant (P<0.05). Compared with the ineffective group of BMMSC infusion, the serum TNF-αlevel in the BMMSCs treatment effective group was 10.8±5.6 pg/ml vs 40.6±14.8 pg/ml (t=-3.901, P<0.05) before treatment. In the effective group of BMMSCs infusion, IL-10 20±17.4 pg/ml of day 14 was significantly higher than that 7.3±3.1 pg/ml before the treatment (t=-2.850, P<0.05), while , the serum levels of IL-2α, IL-6, IL-8, TNF-α were not statistically significantly different (P>0.05)., Conclusion: The infusion of BMMSC is safe and effective in the treatment of refractory GVHD in children. TNF-αlevel relates with the severity of GVHD. BMMSC may play an anti-GVHD role by up regulating the level of cytokine IL-10 in vivo.- Published
- 2020
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35. [Clinical Analysis of 164 Children of Blood Disease Complicated with Invasive Fungal Disease].
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Liao XY, Qiu KY, Wu RH, Guo SY, Wang J, Huang K, Xu HG, Li Y, Fang JP, and Zhou DH
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- Amphotericin B, Antifungal Agents, Child, Humans, Retrospective Studies, Hematologic Diseases etiology, Invasive Fungal Infections complications
- Abstract
Objective: To investigate the clinical characteristics, prevention and treatment of invasive fungal disease (IFD)., Methods: The clinical data of 164 patients who met the diagnostic criteria of IFD in our center from January 2012 to January 2015 were retrospectively analyzed. The incidence, clinical characteristics, related factors, treatment methods and prognosis were analyzed., Results: Among 1289 cases of blood diseases, 164 cases suffered from IFD with inciduce of 12.7%. The main infection sites were as followed: lung, blood and gastrointestinal tract, with incidence of 84.2%, 5.5% and 3% respectively. The funge was found in 35 cases by detection; among fungi, the detected rate of candida albicans. aspergillus and candida glabrata was more high with 51.5%, 20% and 14.3% respectively. Among 164 childen with blood deseases complicated by IFD, 36 cases gained complete remission, 97 cases gained partial remission, 10 cases were stable, 11 cases were progressive and 10 cases died, the overall effective rate reached 81.1%. The univariate analysis showed that the gramulopenia, granulocyte recovery, long-term use of corticosteroid and immuno-suppressive agents, as well as different grades of diagnosis were significant factors affecting the efficacy of antifungal therapy for blood disease children with IFD, the multivariate analysis further showed that the granulocyte recovery and diagnosis grades were independent prognostic factors affecting the therapeutic efficacy for IFD children. The overall survival rate of IFD children with 12 weeks of antifungal treatnment was 81.7%, out of which the survival rate of IFD children at 12 weeks of treatment with itraconazole, voriconazole, amphotericin B and caspofungin was 81.4%, 80%, 69.4% and 97.1% respectively, there were significant differences in survival rate between each other by long rank test. In addition of caspofungin, the other 3 kinds of drugs had toxic side effects of different degrees, but IFD children could tolerated these effects after symptomatic treatment., Conclusion: The incidence of IFD in children with blood deseases in our hospital is 12.7%, the lung is most common infective site, moreover patogens of IFD mainly is candida. The promotion of granulocyte recovery and early stratified diagnosis can contribule to the treatment of IFD. For the IFD children with better economic condition, the caspofungin is a potent antifungal agent with high efficacy, low toxicity and better prognosis.
- Published
- 2019
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36. [Clinical Charcteristics and Prognostic Analysis of 28 cases of Pediatric Myelodysplastic Syndrome].
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Wang J, Lin SF, Chen QH, Qiu KY, Xu HG, Huang K, Li Y, Fang JP, and Zhou ZD
- Subjects
- Child, Female, Hematopoietic Stem Cell Transplantation, Humans, Karyotyping, Male, Prognosis, Retrospective Studies, Myelodysplastic Syndromes
- Abstract
Objective: To analyze the clinical features and prognosis of 28 children with myelodysplastic syndrome (MDS) and to screen the high risk factors affecting the prognosis so as to provide the new ideas for standard of clinical diagnosis and therapy., Methods: The clinical data of 28 children with newly diagnosed MDS treated in our hospital from March 1994 to July 2016 were analyzed retrospectively, the features of disease onset and the results of laboratory examination were summarized, all MDS children were followed up, the prognosis and the high risk factors affecting the prognosis were evaluated., Results: In all 28 MDS children, the ratio of male to female was 1.8∶1, the incidence of MDS was observed in boys, while the low incidence of MDS was found in older children. The clinical manifestations were mainly the decrease of three series blood cells in 16 cases (57.14%), other cases presented simple anemia (7.1%), simple thrombocytopenia (7.1%), neutropenia with anemia (14.29%), and anemia with thrombocytopenia (14.28%).The bone marrow image showed mainly hyperplasia (82.14%), and the pathological hematopoiesis, moreover the manifistation of pathological hematopoiesis was different in forma and degree; the bone marrow biopsy showed the typical abnormal localization of immature precursor(ALIP) accepted for 33.33%; the chromosome karyotype detection showed the detected rate of chronosome abnormality was 41.18%. The median follow-up time was 1.75 years. 5 children with MDS received the hematopoietic stem cell transplantation (HSCT), among them 1 dead and 4 maintained CCR; Out of other 23 patients no-received HSCT, 7 cases given up treatment after confirmed diagnosis, 16 cases received the chemotherapy (2 cases given up treatment after CR, 5 cases transformed into AML, 3 cases relapsed, 3 cases maintained CCR), 11 cases dead, 9 cases failed to be followed up. The 5-years OS rate and EFS rate in all patients were predicted as (38.2±11.3)% and (35.3±11.3)%,respectively, among them, the OS and EFS rates of patients received the HSCT allo superior to those of patients did not received HSCT [(80.0±17.9)% vs.(22.8±11.5)%] (P<0.05) and [(80.0±17.9)% vs (17.5±11.1)%](P<0.05). Analysis showed that in addition to receiving the HSCT(P<0.05), platelet decrease in peripheral blood(P<0.01), the age, sex, existance of micromegakaryocytes in bone marrow and progressive MDS or no influenced not on the prognosis(P>0.05)., Conclusion: The children MDS is rare and easy to be misdiagnosis, moreover displays more high heterogeneity and poor prognosis, thereby the early diagnosis is crucial, in addition, the system of prognosis evaluation is imperative to be perfected. The HSCT may be the effective method for curative treatment of childhood MDS.
- Published
- 2018
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37. [Etiological Study of Late Onset Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation in Children].
- Author
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Deng LL, Qiu KY, Liao XY, Liang YW, Huang K, Li Y, Xu HG, Fang JP, and Zhou DH
- Subjects
- Child, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Hemorrhage, Humans, Incidence, Risk Factors, Transplantation, Homologous, Cystitis
- Abstract
Objective: To prospectively study the correlation BKV with the occurrence and development of late onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation(allo-HSCT)., Methods: The clinical data of a total of 276 patients with allo-HSCT in our department between January 1998 and March 2016 were analyzed ratrospectvely. Quantitative Real-time PCR assay was used to prospectively monitor the BKV DNA load of the urine and plasma for 23 patients accepting allo-HSCT from August 2015 to March 2016., Results: LOHC(24.28%) occurred in 67 of 276 cases with allo-HSCT. Univariate analysis showed that age older than 6 years, different diseases, unrelated donor, pretreatment with BU, Ⅲ-Ⅳ aGVHD significantly correlated with LOHC. Multivariate analysis demonstrated that age older than 6 years (P<0.01), pretreatment with BU(P<0.05), and aGVHD of grade Ⅲ-Ⅳ (P= 0.011) were the independent risk factors for LOHC. Among 23 patients after allo-HSTC, 10 of which were positive of urine BKV, and LOHC occurred in 6 cases. The positive rate of urine BKV (85.7%)in group LOHC
+ was significantly higher than that in the group LOHC- (25.0%)(χ2 =5.043, P<0.01). The incidence of LOHC positively correlated with the positive rate of BKV (r=0.564, P<0.01), and the severity of LOHC positively correlated with urinary BKV load (r = 0.502, P<0.01). And 5 of 6 petriatic patients with LOHC had aGVHD. All of them were subject to the strengthened antiviral treatment, and 4 of them accepted intensive immunosuppression therapy., Conclusion: Age ≥6 years old, precenditioning regieme with BU and aGVHD of grade Ⅲ-Ⅳ are independent risk factors for LOHC after allo-HSCT, the positive rate of urine BKV load positively correlates with the severity of LOHC after allo-HSCT.- Published
- 2018
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38. [Efficacy and Safety of MSC Infusion in Treatment of Children with Refractory LOHC: A Clinical Study].
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Qiu KY, Liao XY, Guo SY, Qi HN, Lan JJ, Fang JP, Huang K, Li Y, Xu HG, and Zhou DH
- Subjects
- Child, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Mesenchymal Stem Cell Transplantation, Retrospective Studies, Transplantation, Homologous, Treatment Outcome, Cystitis
- Abstract
Objective: To study the curative effect and safety of menchymal stem cell infusion in treatment of children with refractory late-onset hemorrhagic cystitis(LOHC) after allogeneic HSCT., Methods: Thirty cases of children with refractory LOHC after allo-HSCT in our department between December 2010 and July 2016 were analyzed retrospectively, out of 30 cases 7 received MSC treatment. The used MSC of all were four-to-five generation MSC from bone marrows of third party donors, and were infused into patients with (1.87±0.456)×10
6 /kg MSCs once a week (1-4 times in total) until the hematuria and odynuria symptoms being improved. To observe whether unfavorable reactions occurred after MSC treatment, the patients accepted daily physical examination and regular assistant examination. The cytokine levels were also measured and dynamically detected in 2 cases before and after MSC treatment., Results: In 30 children with refractory LOHC, the hematuria difficultly reached the remission after routine hydration, alkalizing and antiviral therapy, Among 25 cases who were received methylprednisolone, MTX and CTX therapy, 7 cases received MSC infusion for 1-4 times with dose of (1.87±0.456)×106 /(kg·time) as a result, 7 cases of LOHC were cured. The TNF-α and IL-2R levels in 2 cases progressively decreased after MSC infusion, no occurence of fever, rash, embolism and so on were found in 7 cases received MSC infusion; the BKV detection showed that the viral load did not increase; the leukemia relapse or secondary cancer did not occure., Conclusion: The MSC treatment is safe and effective for refractory LOHC after allo-HSCT.- Published
- 2018
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39. [Clinical Efficacy of NOPHO-AML 2004 Regimen for Treatment of Children with Acute Myelocytic Leukemia (Non-M3)].
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Qiu KY, Liao XY, Huang K, Li Y, Weng WJ, Xu HG, Fang JP, Wu RH, and Zhou DH
- Subjects
- Adolescent, Child, Child, Preschool, Disease-Free Survival, Hematopoietic Stem Cell Transplantation, Humans, Infant, Prognosis, Remission Induction, Treatment Outcome, Leukemia, Myeloid, Acute
- Abstract
Objective: To investigate the efficacy and safety of NOPHO-AML 2004 chemotherapy regimen for treatment of children with acute myelocytic leukemia(non-M3)., Methods: Thirty-three patients aged 1-13 with acute myelocytic leukemia (non-M3) were diagnosed from January 2013 to June 2017. FAB typing showed that 1 case in M0, 4 cases in M1, 12 cases in M2, 5 cases in M4, 8 cases in M5, 1 case in M6, and 2 cases in M7; Risk stratification showed that: 19 cases in standard risk, and 14 cases in high risk. All patients were treated with NOPHO-AML 2004 chemotherapy regimen. SPSS 22.0 software was used, the Kaplan-Meier survival analysis method and Cox regression model were used for statistical analysis., Results: In the first course of treatment (AIET), among 33 child patients there were 27 cases with complete remission, and 5 cases with non-remission, thus the remission rate was 81.8%. Out of the 5 child patients without remission, 4 cases reached to the complete remission after the second course (AM), and 1 case did not remission, thus the total remission rate was 96.9%.9 cases (27.3%) underwent bone marrow recurrence and the median recurrence time was 30 months after complete continuous remission. Univariate analysis showed that age and erythrocyte transfusion frequency were significant factors to affect the early treatment response; the multiple Cox regression analysis showed that: age >7, MRD positive, erythrocyte transfusion >4 times and poor response to early treatment were independent risk factors for recurrence; Allogeneic hematopoietic stem cell transplantation(HSCT) in 8 high-risk children received enhanced chemotherapy had better efficacy as compared with the chemotherapy alone. The 3-year event-free survival rate was 59.9%, and 3-year overall survival rate was 69.2%. 33 children patients experienced varying degrees of infection and myelosuppression, or drug-related gastrointestinal reactions and allergic reactions, patients were tolerable to these side reactions after active symptomatic treatment., Conclusion: NOPHO-AML 2004 chemotherapy regimen has high response rate and good tolerance, early treatment response is an important factor influencing prognosis. Age and repeated red blood cell infusions are the important factors influencing the prognosis, which promote bone marrow recurrence in AML children. For the children suffered from clinical high-risk AML, the NOPHO-AML 2004 chemotherapy regimen combined with HSCT can improve the prognosis of patients.
- Published
- 2018
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40. [Expression Changes of Hepcidin and Ferroportin 1 in Murine Model of Iron Overload].
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Wang JW, Xu LH, Yao X, and Fang JP
- Subjects
- Animals, Disease Models, Animal, Mice, Mice, Inbred C57BL, Cation Transport Proteins metabolism, Hepcidins metabolism, Iron Overload metabolism
- Abstract
Objective: To investigate the changes of hepcidin and ferropotin 1 expression in murine model of iron overload., Methods: The murine model of iron overload was established, C57BL/6 mice were injected with iron dextran intraperitoneally (10 mg) every 3 days for 4 weeks. Blood routine, serum ferritin and pathological sections were tested at the appointed time-point respectively (before iron injection, 2 weeks and 4 weeks after treatment of iron injection). The serum hepcidin was assayed by enzyme-linked immunosorbent method. The expression of ferroportin 1 in bone marrow cells was detected by RT-PCR and Western blot, respectively. The labile iron pool of bone marrow cells was measured by flow cytometry., Results: The absolute number and percentage of reticulocytes in the iron-overloaded mice were significantly decreased along with the increase of iron injection times (r=-0.938, r=-0.947), while no significant change was found in the number of white blood cells, hemoglobin level and platelet count. The level of serum ferritin was increased along with increase of iron injection time (r=0.894). Iron overload was found in pathological sections of different organs. Furthermore, serum hepcidin was increased along with increase of iron injection time (r=0.957). RT-PCR and Western blot analyses showed that the expressions of ferroportin 1 at mRNA and protein level were increased in the murine model of iron overload (P<0.05). Labile iron pool in bone marrow cells was also found to be increased in the murine model of iron overload(P<0.05)., Conclusion: The expressions of hepcidin and ferroportin 1 are increase in a murine model of iron overload, which may be contributed to the suppression effect on erythropoiesis in bone marrow.
- Published
- 2017
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41. [Comparison of the anti-leukemia effect and mechanism of L-asparaginase between two different strains].
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Wang KM, Xu HG, Guo HX, Jin SW, Luo XQ, and Fang JP
- Subjects
- Flow Cytometry, Humans, Jurkat Cells, Apoptosis drug effects, Asparaginase pharmacology, Cell Proliferation drug effects
- Abstract
This study was purposed to compare the anti-leukemic effects of E.coli-L-Asp and Erwinia-L-Asp in vitro, and to investigate their mechanism. The cell apoptosis and proliferation inhibition rate were measured by CCK-8 kit, and IC50 of two drugs was calculated by using SPSS software. Pro-apoptosis effect of E.coli-L-Asp and Erwinia-L-Asp on REH and Jurkat cell lines was also determined by flow cytometry with Annexin V/PI double staining. Concentration changes of 4 amino acids (Asn, Aspa, Gln, and Glu) before and after medication were detected by using high pressure liquid chromatography (HPLC) assay. The results showed that both REH and Jurkat cell lines were sensitive to L-Asp drugs from two different strains, and E.coli-L-Asp and Erwinia-L-Asp displayed the inhibition effect on the proliferation of Jurkat and REH cell lines in dose-dependent and time-dependent manners. The inhibition cell of proliferation and cell apoptosis in Erwinia-L-Asp group were higher than those in E.coli-L-Asp group after 24 hours (P < 0.05) . However, after treatment of REN and Jurkat cells with 2 kind of L-Asp for 48 hours, the inhibition of cell proliferation and apoptosis rates were not significantly different between the 2 L-Asp drugs (P > 0.05). The Asn in medium could be depleted by two different L-Asp drugs with low concentration. Both the two L-Asp drugs had the same capability to deplete the Asn surrounding leukemia cells (P > 0.05). The Gln in medium could be depleted by two L-Asp drugs with high concentration. The hydrolysis effect of Erwinia-L-Asp on Gln was stronger than that of E.coli-L-Asp (P < 0.05). It is concluded that in a certain range of concentrations, E.coli-L-Asp and Erwinia-L-Asp exert anti-leukemia effect in dose-dependent manner. Depletion of Gln and Asn in surrounding environment and induction of cell apoptosis are two potential mechanisms, by which leukemia cells can be killed. Erwinia-L-Asp may be chosen as the first-line drug to treat childhood ALL for its fast action and stronger hydrolysis effect on Gln.
- Published
- 2014
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42. [Influence of blocking B7/CD28 and CD40/CD154 co-stimulatory signals on immune function of sensitized mice].
- Author
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Ye QX, Xu LH, Xu W, and Fang JP
- Subjects
- Animals, B7-1 Antigen metabolism, Bone Marrow Transplantation, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Signal Transduction, Transplantation, Homologous, CD28 Antigens metabolism, CD40 Antigens metabolism, CD40 Ligand metabolism, Immune Tolerance immunology
- Abstract
This study was aimed to explore the effects of blocking B7/CD28 and CD40/CD154 co-stimulatory signals on immune function of sensitized mice', and provide the evidences of acquired immune tolerance for allogeneic bone marrow transplantation. The mice sensitized on 7 day before transplant were divided into 4 groups: (1)CTLA4Ig+ anti-CD154 isotype control IgG; (2)anti-CD154 +CTLA4Ig isotype control IgG; (3)CTLA4Ig and anti-CD154; (4)isotype control IgG of CTLA4Ig and anti-CD154. CTLA4Ig and anti-CD154 used in normal BALB/c mice as isotype control IgG. Each mouse in all groups received CTLA4Ig and anti-CD154 (or corresponding isotype control IgG) 500 µg respectively, and was injected via tail vein on 7 day before transplant. There were 5 mice in each group. The mice were sacrificed on day 0, then the number of CD19(+)CD69(+)B cells, CD44(high)/CD62L(high) and CD44(high)/CD62L(low)/- T cells were measured by flow cytometry. Changes of cytokines and sensitized antibody were tested by ELISA or flow cytometry. The results showed that the numbers of CD19(+)CD69(+)B cells were significantly increased in comparison with the normal group (P < 0.01) , whereas the numbers of cells were significantly decreased when blocking B7/CD28 or /and CD40/CD154 co-stimulatory signals (P < 0.01) . Blocking these 2 signals together displayed a synergistic effect (P < 0.01) . The central memory and effector T cells were defined as CD44(high)/CD62L(high) and CD44(high)/CD62L(low)/- respectively, those increased significantly after sensitized in comparison with those in normal group, whereas their numbers decreased when blocking B7/CD28 or/and CD40/CD154 co-stimulatory signals. Blocking these two signals together, displayed a synergistic effect (P < 0.01). Cytokines, IgG and IgM in all groups were not significantly different. Sensitizing antibody test showed that the fluorescence intensity of sensitized group significantly increased as compared with normal group, whereas fluorescence intensity of CTLA4Ig or/and anti-CD154 treated groups significantly decreased as compared with sensitized group (P < 0.01) . It is concluded that blocking the B7/CD28 or/and CD40/CD154 co-stimulatory signal can inhibit the cellular and humoral immune function, whereas blocking these two signals together displays a synergistic effect.
- Published
- 2014
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43. [Relation of Treg and iNKT cell reconstruction with aGVHD after allogeneic hematopoietic stem cell transplantation in children].
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Wang PF, Huang K, Fang JP, Zhou DH, Guo HX, Chen YY, Chen C, and Li Y
- Subjects
- Child, Child, Preschool, Early Diagnosis, Female, Hematopoietic Stem Cell Transplantation, Humans, Male, Transplantation, Homologous, Graft vs Host Disease diagnosis, Natural Killer T-Cells cytology, T-Lymphocytes, Regulatory cytology
- Abstract
This study was aimed to explore the relation of Treg and invariant natural killer T (iNKT) cell reconstruction with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. According to the occurrence or absence of aGVHD, 29 pediatric patients who underwent allo-HSCT were firstly divided into two groups non-aGVHD and aGVHD group,then those patients with aGVHD were divided into steroid effective group and steroid resistant group according to their reaction to the steroid treatment. Flow cytometry was used to detect the frequency of Treg cells and iNKT cells in the peripheral blood of the recipients at different time after allo-HSCT(d 15, d 30, d 60, d 90, the time of aGVHD onset and two weeks after steroid treatment). The result showed that the frequencies of Treg cells and the iNKT/T ratio on day 15 in non-aGVHD group were significantly higher than those in the aGVHD group (P < 0.05). It is concluded that a combined monitoring strategy of Treg and iNKT cell reconstruction early after allo-HSCT may facilitate the diagnosis and treatment of aGVHD in children.
- Published
- 2014
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44. [Effects of CD4(+)CD25(+) regulatory T cells on allogeneic hematopoietic stem cell transplantation in sensitized mice].
- Author
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Ye QX, Weng WJ, Xu LH, and Fang JP
- Subjects
- Animals, Graft vs Host Disease etiology, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation methods, Immune Tolerance, T-Lymphocytes, Regulatory immunology
- Abstract
The aim of this study was to investigate the effects of CD4(+)CD25(+) regulatory T cells (Treg) on allogeneic hematopoietic stem cell transplantation (HSCT) in sensitized mice so as to provide experimental evidence for clinical treatment of allogeneic HSCT rejection in sensitized recipients. The BALB/c mice were divided into 5 groups: group A - mice were sensitized with injection of splenocytes; group B - mice were sensitized with splenocytes and treated with >5×10(5) Treg on day 7 before transplantation; group C - mice were sensitized with splenocytes and treated with 5×10(5) Treg on day 13 and 7 before transplantation; group D - mice were not sensitized, but treated with equal volume of PBS as control; group E - blank control. Each group had 15 mice. On day 0 of transplantation, mice in each group were irradiated lethally with 8 Gy by linear accelerator, and the bone marrow cells of C57BL/6 labeled by fluorescence staining were intravenously injected via the tail vein. The fluorescent cells in peripheral blood and organ tissue were detected by flow cytometry on different time points for homing assessment. Survival rates and hematopoietic reconstitution were also recorded and monitored. The results showed that on 12 and 24 hours after transplantation, as compared with the sensitized group, the number of fluorescence homing cells in different tissue of the applied Treg groups increased significantly and the differences were statistically significant (P < 0.05). The mice in sensitized group and blank control group all died on the 6-13 day, whereas the median survival time of mice in applied Treg once and twice were 15 days and 16 days respectively. Comparing with sensitized group, the difference was statistically significant (P < 0.001), but there was no significant difference between these two groups applied regulatory T cell (P > 0.05). It is concluded that applying Treg can induce immune tolerance of sensitized recipient to allogeneic HSCT and inhibit immune destruction and prolong the survival time, but can not induce full immune tolerance and at last sensitized mice died of rejection of hematopoietic stem cells.
- Published
- 2014
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45. [Effects of blocking co-stimulatory signals on immunotolerance rejection of sensitized recipient after hematopoietic stem cell transplantation].
- Author
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Ye QX, Weng WJ, Xu LH, and Fang JP
- Subjects
- Abatacept, Animals, B7 Antigens antagonists & inhibitors, CD28 Antigens antagonists & inhibitors, CD40 Antigens antagonists & inhibitors, CD40 Ligand antagonists & inhibitors, Immunoconjugates pharmacology, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Transplantation, Homologous, Graft Rejection prevention & control, Hematopoietic Stem Cell Transplantation, Immune Tolerance
- Abstract
This research was aimed to explore the effects of blocking B7/CD28 and CD40/CD154 co-stimulatory signals on engraftment of hematopoietic stem cell in the sensitized recipient so as to provide the experimental evidence for the treatment of sensitized recipient's immune rejection after clinical allogeneic hematopoietic stem cell transplantation (HSCT). The BALB/c mice were divided into 4 groups: (1)mice sensitized on 7 day before transplant; (2)mice were sensitized on 7 day before transplant, and injected CTLA4Ig+anti-CD154 applied; (3)normal mice injected by corresponding isotype control IgG of CTLA4Ig and anti-CD154; (4)normal blank control mice. Each group had 15 mice. On day 0, mice of each group were irradiated lethally 8 Gy by linear accelerator, and the bone marrow cells of C57BL/6 labeled by fluorescence staining were injected via the tail vein. The fluorescent cell level in peripheral blood and organ tissue at different time points were detected by flow cytometry (FCM) for homing assessment. Survival rates and hematopoietic reconstitution were also monitored and recorded. The results showed that application of CTLA4Ig anti-CD154 could promote implantation of allogeneic HSC in sensitized recipients, induce the immune tolerance, prolong their survival time and accelerate the hematopoietic reconstitution within 28 days, compared with the sensitized group. It is concluded that applying CTLA4Ig and anti-CD154 can enhance the engraftment of HSCT and induce immune tolerance in the sensitized recipient after allogeneic HSCT and accelerate the hematopoietic reconstitution.
- Published
- 2014
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46. [In vitro amplification of CD4(+) CD25(+) regulatory T cells and identification of amplified T cell immunosuppressive function].
- Author
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Weng WJ, Pan L, Fang JP, and Xu LH
- Subjects
- Animals, Cells, Cultured, Flow Cytometry, Forkhead Transcription Factors metabolism, Interleukin-2 Receptor alpha Subunit immunology, Lymphocyte Culture Test, Mixed, Male, Mice, Mice, Inbred BALB C, T-Lymphocytes, Regulatory cytology, Cell Proliferation, T-Lymphocytes, Regulatory immunology
- Abstract
This study was purposed to compare the effect of 3 different cell components for expanding CD4(+) CD25(+) Treg in vitro, and identify their immunosuppressive function. CD4(+) T cells, CD4(+) CD25(-)T cells and CD4(+) CD25(+)T cells were isolated from mouse splenocytes by MACS and then expanded in vitro. Phenotype of the T cell lines and expression of the FOXP3 was determined by flow cytometry. The inhibitory effect of expanded CD4(+) CD25(+) T cells on CD4(+) CD25(-)T cells was tested by MLR method. The results showed that the Treg cells from all the three groups were expanded significantly after culture for 2 weeks. In the CD4(+) T cells group, the proliferation rate was (77.8 ± 5.32) folds with a percentage of Treg cells increasing from (6.61 ± 1.00)% to (15.33 ± 1.31)%. The proliferation rate in the CD4(+) CD25(-) T cells group was (95.20 ± 7.67) folds, with the percentage of CD4(+) CD25(+) T cells raising from (0.37 ± 0.13)% to (9.84 ± 0.98)%. The proliferation rate in the CD4(+) CD25(+) T cells group was (41.20 ± 6.92) folds, the proportion of Treg cells decreased from (86.75 ± 1.25)% to (85.32 ± 1.62)%, and the expression of Foxp3 decreased from (76.92 ± 1.72)% to (75.33 ± 2.11)% during the culture, there were not significant differences in the cell purity and the expression of Foxp3, compared with pre-amplification. The inhibitory test showed that the expanded CD4(+) CD25(+) T cells could inhibit the proliferation of CD4(+) CD25(-) T cells in vitro in a cell dose-dependent manner. It is concluded that the amplification of CD4(+) CD25(+) Treg cells is successful in vitro, especially in the CD4(+) CD25(+) T cells group, the cell purity and Foxp3 gene is not obviously changes after amplification.
- Published
- 2013
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47. [Acute leukemia child with ocular Kaposi's sarcoma after hematopoietic stem cell transplantation: a case report and literatures review].
- Author
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Guo HX, Huang K, Zhou DH, Wang L, Xiao JH, Weng WJ, and Fang JP
- Subjects
- Adolescent, Hematopoietic Stem Cell Transplantation, Humans, Male, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Eye Neoplasms, Postoperative Complications, Sarcoma, Kaposi
- Abstract
Objective: To summarize clinical features of eye Kaposis' sarcoma ( KS ) in leukemia child after peripheral blood stem cell transplantation (PBSCT)., Methods: One 13 years-old child with acute lymphoblastic leukemia (ALL) and negative HIV test who developed KS restricted in right conjunctiva, cornea and sclera after successful allogeneic PBSCT was reviewed retrospectively., Results: The child suffered from T cell type ALL. He received immunosuppressive treatment after PBSCT, and had once extensive herpes zoster restricted in skin. Seven months after PBSCT, he had blurred vision with right eye and slowly neoplasm formed in cornea and conjunctiva. Pathological examination confirmed KS with changes like capillary hemangioma, atypical fusiform cell, typical immunochemistry and positive immunofluorescent result of HHV8. He received excision of lump of cornea, conjunctiva, sclera and transplantation of cornea and sclera. Antiviral therapy was given together with anti-infection, prevention of cornea rejection and biotherapy. He kept right eye and hand-move eyesight, survived without GVHD or recurrence of ALL and KS., Conclusion: This was the first ocular KS case in ALL child after PBSCT, without correlation with HIV infection. Complete excision combined with biotherapy was safe and effective for single ocular lesions.
- Published
- 2013
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48. [Therapeutic efficacy evaluation of rabbit anti-thymocyte globulin combined with cyclosporine A in children with aplastic anemia].
- Author
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Fu RT, Xue HM, Xu HG, Huang K, Fang JP, Huang SL, and Chen C
- Subjects
- Adolescent, Antilymphocyte Serum administration & dosage, Child, Child, Preschool, Cyclosporine administration & dosage, Drug Therapy, Combination, Female, Humans, Lymphocyte Count, Lymphocyte Subsets, Male, Retrospective Studies, Treatment Outcome, Anemia, Aplastic drug therapy, Antilymphocyte Serum therapeutic use, Cyclosporine therapeutic use
- Abstract
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.
- Published
- 2013
- Full Text
- View/download PDF
49. [Analysis of one case of adolescent blastic plasmacytoid dendritic cell neoplasm].
- Author
-
Ma L, Li Y, Liu L, Guo HX, Xue HM, Lin SX, Xu HG, Huang SL, Chen C, and Fang JP
- Subjects
- Adolescent, Dendritic Cells, Humans, Male, Hematologic Neoplasms, Skin Neoplasms, Waldenstrom Macroglobulinemia
- Abstract
This study was purposed to summarize the clinical characteristics and laboratorial data of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in pediatric patients in order to enhance understanding this disease in diagnosis and therapy. A rare case of BPDCN in children was enrolled in this study. The blood routine test, examination of bone marrow cell morphology, histopathology and immunophenotype of the skin lesions were performed and analysed, the single cell suspensions of the biopsied skin mass were detected by flow cytometry. The results showed that tumor cells expressed CD4, CD56, CD43 and CD123, while not expressed CD19, CD20, CD3, CD8, CD13, CD11b and myeloperoxidase (MPO). According to the clinical and laboratorial features and the results from histopathological and immunophenotype examinations, BPDCN was confirmed. It is concluded that BPDCN in children is an extremely rare hematopoietic malignancy with presenting a rapidly and fatally aggressive clinical course. The diagnosis of this disease is mainly based on the clinical presentations, pathologic and immunohistochemical features. BPDCN is a highly aggressive disease, its prognosis is very poor, its pathogenesis remans still unclear. A standard treatment protocol for BPDCN has not yet been established.
- Published
- 2013
- Full Text
- View/download PDF
50. [Advances in effect of mitophagy on erythropoiesis].
- Author
-
Xia T, Xu LH, and Fang JP
- Subjects
- Humans, Erythropoiesis physiology, Mitochondria physiology, Mitophagy
- Published
- 2012
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