87 results on '"Lixian Chang"'
Search Results
2. Mutation spectrum, expression profiling, and prognosis evaluation of Fanconi anemia signaling pathway genes for 4259 patients with myelodysplastic syndromes or acute myeloid leukemia
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Lixian Chang, Li Zhang, Beibei Zhao, Xuelian Cheng, Yang Wan, Ranran Zhang, Weiping Yuan, Xingjie Gao, and Xiaofan Zhu
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Fanconi anemia pathway ,AML ,MDS ,Expression ,Mutation ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Individuals diagnosed with Fanconi anemia (FA), an uncommon disorder characterized by chromosomal instability affecting the FA signaling pathway, exhibit heightened vulnerability to the onset of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Methods Herein, we employed diverse bioinformatics and statistical analyses to investigate the potential associations between the expression/mutation patterns of FA pathway genes and MDS/AML. Results The study included 4295 samples, comprising 3235 AML and 1024 MDS from our and nine other online cohorts. We investigated the distinct proportion of race, age, French-American-British, and gender factors. Compared to the FA wild-type group, we observed a decrease in the expression of FNACD2, FANCI, and RAD51C in the FA mutation group. The FA mutation group exhibited a more favorable clinical overall survival prognosis. We developed a random forest classifier and a decision tree based on FA gene expression for cytogenetic risk assessment. Furthermore, we created an FA-related Nomogram to predict survival rates in AML patients. Conclusions This investigation facilitates a deeper understanding of the functional links between FA and MDS/AML.
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- 2023
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3. An investigation of long-term outcome of rabbit anti-thymocyte globulin and cyclosporine therapy for pediatric severe aplastic anemia
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Lixian Chang, Mingchen Yan, Jingliao Zhang, Binghang Liu, Li Zhang, Ye Guo, Jing Sun, Yang Wan, Meihui Yi, Yang Lan, Yuli Cai, Yuanyuan Ren, Haihui Zheng, Aoli Zhang, Zhenyu Li, Jian Wang, Yingrui Li, and Xiaofan Zhu
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Children with severe aplastic anemia (SAA) face heterogeneous prognoses after immunosuppressive therapy (IST). There are few models that can predict the long-term outcomes of IST for these patients. The objective of this paper is to develop a more effective prediction model for SAA prognosis based on clinical electronic medical records from 203 children with newly diagnosed SAA. In the early stage, a novel model for long-term outcomes of SAA patients with IST was developed using machine-learning techniques. Among the indicators related to long-term efficacy, white blood cell count, lymphocyte count, absolute reticulocyte count, lymphocyte ratio in bone-marrow smears, C-reactive protein, and the level of IL-6, IL-8 and vitamin B12 in the early stage are strongly correlated with long-term efficacy (P < .05). Taken together, we analyzed the long-term outcomes of rabbit anti-thymocyte globulin and cyclosporine therapy for children with SAA through machine-learning techniques, which may shorten the observation period of therapeutic effects and reduce treatment costs and time.
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- 2023
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4. P792: CLINICAL STUDY OF HETROMBOPAG COMBINED WITH CYCLOSPORINE A IN THE TREATMENT OF CHILDREN WITH NON-SEVERE APLASTIC ANEMIA
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Lixian Chang, LI Zhang, Yao Zou, Yumei Chen, Ye Guo, Xiaojuan Chen, Wenyu Yang, Ranran Zhang, Yang Wan, Beibei Zhao, Ruan Min, Xiaoming Liu, and Xiaofan Zhu
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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5. Polyclonal evolution of Fanconi anemia to MDS and AML revealed at single cell resolution
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Lixian Chang, Zejia Cui, Deyang Shi, Yajing Chu, Bichen Wang, Yang Wan, Qiuyi Ma, Ranran Zhang, Haoyuan Li, Xuelian Cheng, Tao Cheng, Xiaofan Zhu, Cheng Li, and Weiping Yuan
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Fanconi anemia ,Myelodysplastic syndromes ,Acute myeloid leukemia ,Clonal evolution ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Fanconi anemia (FA) is a rare disease of bone marrow failure. FA patients are prone to develop myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, the molecular clonal evolution of the progression from FA to MDS/AML remains elusive. Methods Herein, we performed a comprehensive genomic analysis using an FA patient (P1001) sample that transformed to MDS and subsequently AML, together with other three FA patient samples at the MDS stage. Results Our finding showed the existence of polyclonal pattern in these cases at MDS stage. The clonal evolution analysis of FA case (P1001) showed the mutations of UBASH3A, SF3B1, RUNX1 and ASXL1 gradually appeared at the later stage of MDS, while the IDH2 alteration become the dominant clone at the leukemia stage. Moreover, single-cell sequencing analyses further demonstrated a polyclonal pattern was present at either MDS or AML stages, whereas IDH2 mutated cell clones appeared only at the leukemia stage. Conclusions We thus propose a clonal evolution model from FA to MDS and AML for this patient. The results of our study on the clonal evolution and mutated genes of the progression of FA to AML are conducive to understanding the progression of the disease that still perplexes us.
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- 2022
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6. Decoding the pathogenesis of Diamond–Blackfan anemia using single-cell RNA-seq
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Bingrui Wang, Chenchen Wang, Yang Wan, Jie Gao, Yige Ma, Yingnan Zhang, Jingyuan Tong, Yingchi Zhang, Jinhua Liu, Lixian Chang, Changlu Xu, Biao Shen, Yumei Chen, Erlie Jiang, Ryo Kurita, Yukio Nakamura, Kim-Chew Lim, James Douglas Engel, Jiaxi Zhou, Tao Cheng, Xiaofan Zhu, Ping Zhu, and Lihong Shi
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Cytology ,QH573-671 - Abstract
Abstract Ribosomal protein dysfunction causes diverse human diseases, including Diamond–Blackfan anemia (DBA). Despite the universal need for ribosomes in all cell types, the mechanisms underlying ribosomopathies, which are characterized by tissue-specific defects, are still poorly understood. In the present study, we analyzed the transcriptomes of single purified erythroid progenitors isolated from the bone marrow of DBA patients. These patients were categorized into untreated, glucocorticoid (GC)-responsive and GC-non-responsive groups. We found that erythroid progenitors from untreated DBA patients entered S-phase of the cell cycle under considerable duress, resulting in replication stress and the activation of P53 signaling. In contrast, cell cycle progression was inhibited through induction of the type 1 interferon pathway in treated, GC-responsive patients, but not in GC-non-responsive patients. Notably, a low dose of interferon alpha treatment stimulated the production of erythrocytes derived from DBA patients. By linking the innately shorter cell cycle of erythroid progenitors to DBA pathogenesis, we demonstrated that interferon-mediated cell cycle control underlies the clinical efficacy of glucocorticoids. Our study suggests that interferon administration may constitute a new alternative therapeutic strategy for the treatment of DBA. The trial was registered at www.chictr.org.cn as ChiCTR2000038510.
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- 2022
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7. Pediatric non–Down’s syndrome acute megakaryoblastic leukemia patients in China: A single center's real-world analysis
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Aoli Zhang, Lipeng Liu, Suyu Zong, Xiaoyan Chen, Chao Liu, Lixian Chang, Xiaojuan Chen, Wenyu Yang, Ye Guo, Li Zhang, Yao Zou, Yumei Chen, Yingchi Zhang, Min Ruan, and Xiaofan Zhu
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non-DS-AMKL ,pediatric ,treatment ,outcomes ,prognostic factors ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Non-Down’s syndrome acute megakaryocytic leukemia (non-DS-AMKL) is a subtype of childhood acute myeloid leukemia (AML), whose prognosis, prognostic factors and treatment recommendations have not yet to be defined in children. We conducted a retrospective study with 65 newly diagnosed non-DS-AMKL children from August 2003 to June 2020 to investigate the clinical impact of factors and clinical outcome. Among all 65 patients, 47 of them were treated at our center who received three different regimens due to time point of admission (CAMS-another, CAMS-2009 and CAMS-2016 protocol), and the efficacy were compared. Patients with newly diagnosed non-DS-AMKL accounted for 7.4% of pediatric AML cases. The median age of the patients was 18 months at diagnosis, and over 90% of them were under three-years-old. The overall survival (OS) rates were 33.3% ± 1.7%, 66.7% ± 24.4% and 74.2% ± 4.0% for three groups (CAMS-another, CAMS-2009 and CAMS-2016 regimen), respectively. In CAMS-2016 group, the complete remission (CR) rate after induction was 67.7% (21/31), while the total CR rate after all phases of chemotherapy was 80.6% (25/31). The 2-year survival probability did not significantly improve in patients underwent HSCT when compared with non-HSCT group (75.0% ± 4.7% vs. 73.9% ± 4.6%, p=0.680). Those who had a “dry tap” during BM aspiration at admission had significantly worse OS than those without “dry tap” (33.3% ± 8.6% vs. 84.0% ± 3.6%, p=0.006). Moreover, the results also revealed that patients with CD34+ had significantly lower OS (50.0% ± 6.7% vs. 89.5% ± 3.5%, p=0.021), whereas patients with CD36+ had significantly higher OS than those who were negative (85.0% ± 4.0% vs. 54.5% ± 6.6%, p=0.048). In conclusion, intensive chemotherapy resulted in improved prognosis of non-DS-AMKL children and subclassification may base on “dry tap” and immunophenotypic. Although some progress has been made, outcomes of non-DS-AMKL children remain unsatisfactory, especially in HSCT group, when compared with other AML types.
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- 2022
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8. DNAH2 facilitates the homologous recombination repair of Fanconi anemia pathway through modulating FANCD2 ubiquitination
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Lixian Chang, Xingjie Gao, Yuxia Wang, Chunmin Huang, Min Gao, Xiaomin Wang, Chao Liu, Wenqi Wu, Wenbin An, Yang Wan, Aoli Zhang, Yingchi Zhang, Weiping Yuan, and Xiaofan Zhu
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract. Fanconi anemia (FA), an X-linked genetic or autosomal recessive disease, exhibits complicated pathogenesis. Previously, we detected the mutated Dynein Axonemal Heavy Chain 2 (DNAH2) gene in 2 FA cases. Herein, we further investigated the potential association between DNAH2 and the homologous recombination repair pathway of FA. The assays of homologous recombination repair, mitomycin C (MMC) sensitivity, immunofluorescence, and ubiquitination modification were performed in U2OS and DR-U2OS cell lines. In MMC-treated U2OS cells, the downregulation of the DNAH2 gene increased the sensitivity of cells to DNA inter-strand crosslinks. We also observed the reduced enrichment of FANCD2 protein to DNA damage sites. Furthermore, the ubiquitination modification level of FANCD2 was influenced by the deficiency of DNAH2. Thus, our results suggest that DNAH2 may modulate the cell homologous recombination repair partially by increasing the ubiquitination and the enrichment to DNA damage sites of FANCD2. DNAH2 may act as a novel co-pathogenic gene of FA patients.
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- 2021
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9. Combination of umbilical cord mesenchymal stem cells and standard immunosuppressive regimen for pediatric patients with severe aplastic anemia
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Yang Lan, Fang Liu, Lixian Chang, Lipeng Liu, Yingchi Zhang, Meihui Yi, Yuli Cai, Jing Feng, Zhibo Han, Zhongchao Han, and Xiaofan Zhu
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Child ,Immunosuppressive therapy ,Mesenchymal stem cell ,Severe aplastic anemia ,Umbilical cord ,Pediatrics ,RJ1-570 - Abstract
Abstract Background Defects of bone marrow mesenchymal stem cells (BM-MSCs) in proliferation and differentiation are involved in the pathophysiology of aplastic anemia (AA). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) may improve the efficacy of immunosuppressive therapy (IST) in childhood severe aplastic anemia (SAA). Methods We conducted an investigator-initiated, open-label, and prospective phase IV trial to evaluate the safety and efficacy of combination of allogenic UC-MSCs and standard IST for pediatric patients with newly diagnosed SAA. In mesenchymal stem cells (MSC) group, UC-MSCs were injected intravenously at a dose of 1 × 106/kg per week starting on the 14th day after administration of rabbit antithymocyte globulin (ATG), for a total of 3 weeks. The clinical outcomes and adverse events of patients with UC-MSCs infusion were assessed when compared with a concurrent control group in which patients received standard IST alone. Results Nine patients with a median age of 4 years were enrolled as the group with MSC, while the data of another 9 childhood SAA were analysed as the controls. Four (44%) patients in MSC group developed anaphylactic reactions which were associated with rabbit ATG. When compared with the controls, neither the improvement of blood cell counts, nor the change of T-lymphocytes after IST reached statistical significance in MSC group (both p > 0.05) and there were one (11%) patient in MSC group and two (22%) patients in the controls achieved partial response (PR) at 90 days after IST. After a median follow-up of 48 months, there was no clone evolution occurring in both groups. The 4-year estimated overall survival (OS) rate in two groups were both 88.9% ± 10.5%, while the 4-year estimated failure-free survival (FFS) rate in MSC group was lower than that in the controls (38.1% ± 17.2% vs. 66.7% ± 15.7%, p = 0.153). Conclusions Concomitant use of IST and UC-MSCs in SAA children is safe but may not necessarily improve the early response rate and long-term outcomes. This clinical trial was registered at ClinicalTrials.gov, identifier: NCT02218437 (registered October 2013).
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- 2021
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10. Novel diagnostic approaches for Fanconi anemia (FA) by single-cell sequencing and capillary nano-immunoassay
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Lixian Chang, Xingjie Gao, Guangzhen Ji, Xuelian Cheng, Yao Zou, Tao Cheng, Weiping Yuan, and Xiaofan Zhu
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract. Next-generation sequencing technology has been widely utilized for the diagnosis of Fanconi anemia (FA). However, mixed cell sequencing and chimerism of FA patients may lead to unconfirmed genetic subtypes. Herein, we introduced two novel diagnostic methods, including single-cell sequencing and capillary nano-immunoassay. One FA case with FANCM c.4931G>A p.R1644Q and FANCD1 c.6325G>A p.V2109I was studied. The DNA of 28 cells was amplified and eight types of cells were observed after Sanger sequencing. There were two homozygous mutations (FANCM/FANCD1). Furthermore, the capillary nano-immunoassay was conducted to analyze the expression profile of FA-associated proteins. Abnormal FANCM and FANCD1 expressions simultaneously existed. This case was thus diagnosed as FA-D1/FA-M dual subtype. Compared with mixed cell sequencing, single-cell sequencing data shows more accuracy for the FA subtype evaluation, while the capillary nano-immunoassay is a good method to detect the expression profile of abnormal or modified FA protein.
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- 2021
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11. A Novel Risk Defining System for Pediatric T-Cell Acute Lymphoblastic Leukemia From CCCG-ALL-2015 Group
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Xiaoming Liu, Yao Zou, Li Zhang, Ye Guo, Yumei Chen, Wenyu Yang, Xiaojuan Chen, Shuchun Wang, Yingchi Zhang, Min Ruan, Lixian Chang, Xiaoyan Zhang, Beibei Zhao, Ranran Zhang, Aoli Zhang, Lipeng Liu, Luyang Zhang, Meihui Yi, and Xiaofan Zhu
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children ,T-cell acute lymphoblastic leukemia (T-ALL) ,risk ,efficacy ,CCCG-ALL-2015 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
ObjectiveT-cell acute lymphoblastic leukemia (T-ALL) is a rare hematological malignancy with a poor prognosis. The present study aims to identify the precise risk grouping of children with T-ALL.MethodsWe analyzed the outcomes for 105 consecutive patients treated using the Chinese Children’s Cancer Group ALL-2015 (CCCG-ALL-2015) protocol registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005706) between 2015 and 2020 in our center. Nine out of 21 clinical and biological indicators were selected for the new scoring system based on the analysis in this study.ResultsThe 5-year overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) rates for the 105 patients were 83.1 ± 4.8%, 72.4 ± 5.6%, and 78.4 ± 3.6%, respectively. Based on the new scoring system, 90 evaluable children were regrouped into low-risk (n=22), intermediate-risk (n=50), and high-risk (n=18) groups. The 5-year survival (OS, EFS, and RFS) rates for all patients in the low-risk group were 100%, significantly higher than the rates for those in the intermediate-risk group (91.2 ± 5.2%, 74.4 ± 8.6%, and 82.5 ± 6.2%, respectively) and high-risk group (59.0 ± 13.2%, 51.9 ± 12.4%, and 51.9 ± 12.4%, respectively) (all P values < 0.01).ConclusionThe CCCG-ALL-2015 program significantly improved the treatment outcomes for childhood T-ALL as compared with the CCCG-ALL-2008 protocol. Our new refined risk grouping system showed better stratification among pediatric T-ALL patients and better potential in evaluating therapeutic efficacy.
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- 2022
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12. Targeted Next-Generation Sequencing of Circulating Tumor DNA, Bone Marrow, and Peripheral Blood Mononuclear Cells in Pediatric AML
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Min Ruan, Lipeng Liu, Benquan Qi, Xiaoyan Chen, Lixian Chang, Aoli Zhang, Fang Liu, Shuchun Wang, Xiaoming Liu, Xiaojuan Chen, Li Zhang, Ye Guo, Yao Zou, Yingchi Zhang, Yumei Chen, LiXia Liu, Shanbo Cao, Feng Lou, Chengcheng Wang, and Xiaofan Zhu
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acute myeloid leukemia ,targeted next-generation sequencing ,circulating tumor DNA ,mutation (genetics) ,pediatric ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundThe aim of the study was to validate the diagnostic role of circulating tumor DNA (ctDNA) in genetics aberration on the basis of next-generation sequencing (NGS) in pediatric acute myeloid leukemia (AML).MethodsBone marrow (BM) and peripheral blood (PB) were collected from 20 AML children at the time of initial diagnosis, and a ctDNA sample was isolated from PB. Detection of mutation was performed on ctDNA, BM, and peripheral blood mononuclear cell (PBMC) by NGS based on a 185-gene panel.ResultsAmong 185 genes sequenced by the NGS platform, a total of 82 abnormal genes were identified in 20 patients. Among them, 61 genes (74.39%) were detected in ctDNA, PBMC, and BM samples, while 11 (13.41%) genes were found only in ctDNA and 4 (4.88%) were detected only in the BM sample, and 2 (2.44%) were detected only in PBMC. A total of 239 mutations were detected in three samples, while 209 in ctDNA, 180 in bone marrow, and 184 in PBMC. One hundred sixty-four mutations in ctDNA were shared by matched BM samples, and the median variant allelic frequency (VAF) of these mutations was 41.34% (range, 0.55% to 99.96%) and 44.36% (range, 0.56% to 99.98%) in bone marrow and ctDNA. It was found that 65.79% (75/114) of mutations with clinical significance were detected in three samples, with 9 mutations detected both in ctDNA and BM, and 2 mutations detected both in PBMC and BM. The consistency of mutations with clinical significance between ctDNA and BM was 77.06% (84/109). Among the 84 mutations with clinical significance detected in both sources, the concordance of VAF assessment by both methods was high (R2 = 0.895).ConclusionThis study demonstrates that ctDNA was a reliable sample in pediatric AML and can be used for mutation detection. Consistency analysis showed that ctDNA can mirror the genomic information from BM. In addition, a subset of mutations was exclusively detected in ctDNA. These data support the fact that monitoring ctDNA with next-generation sequencing-based assays can provide more information about gene mutations to guide precision treatment in pediatric AML.
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- 2021
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13. Pediatric Acute Lymphoblastic Leukemia Patients Exhibit Distinctive Alterations in the Gut Microbiota
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Xiaoming Liu, Yao Zou, Min Ruan, Lixian Chang, Xiaojuan Chen, Shuchun Wang, Wenyu Yang, Li Zhang, Ye Guo, Yumei Chen, Yingchi Zhang, Hongrui He, Yu Gan, Kejian Wang, and Xiaofan Zhu
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interleukin-10 ,quantitative PCR ,16S rRNA quantitative microarray ,gut microbiota ,acute lymphoblastic leukemia (ALL) ,Microbiology ,QR1-502 - Abstract
Previous studies have shown that gut microbiota can affect human immune system in many ways. Our aim was to investigate quantitative differences in fecal bacterial compositions of childhood acute lymphoblastic leukemia (ALL) patients compared to those of healthy children, so as to identify individual bacterial species that are related to the etiology of ALL. We recruited 81 subjects, including 58 patients with ALL and 23 healthy controls. Fecal samples were collected and examined by 16S rRNA quantitative arrays and bioinformatics analysis. Both Principal Coordinates Analysis (PCoA) and Non-metric Multidimensional scaling (NMDS) demonstrated that the microbial composition of ALL patients deviated from the tight cluster of healthy controls. Multiple bacterial species exhibited significant changes (e.g., Roseburia faecis, Edwardsiella tarda, and Fusobacterium naviforme) in the ALL samples. Some of the differentially abundant taxa were correlated with the level of interleukin-10. The ALL cases could be efficiently distinguished from healthy controls by the random forest model based on differential species (area under ROC curve = 0.843). Taken together, the composition of gut microbiota differed from healthy controls to pediatric ALL patients. Our study identified a series of ALL-related species in the gut microbiota, providing a new direction for future studies aiming to understand the host-gut microbiota interplay in ALL pathogenesis.
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- 2020
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14. The study of METTL3 and METTL14 expressions in childhood ETV6/RUNX1‐positive acute lymphoblastic leukemia
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Congcong Sun, Lixian Chang, Chao Liu, Xiaoyan Chen, and Xiaofan Zhu
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acute lymphoblastic leukemia ,children ,ETV6/RUNX1 ,METTL14 ,METTL3 ,Genetics ,QH426-470 - Abstract
Abstract Background This study was aimed to explore the METTL3 and METTL14 expressions in children with ETV6/RUNX1(E/R)‐positive acute lymphoblastic leukemia (ALL) and investigate the relation between the METTL3 and METTL14 expressions with clinical features. Methods Thirty‐seven newly diagnosed E/R‐positive ALL children and six controls were included in this study. Real‐time quantitative polymerase chain reaction (RT‐PCR) was used to detect the mRNA expression level of METTL3 and METTL14. Results Among the 37 cases, 51.35% (n = 19) were boys and 48.65% (n = 18) were girls and the median age was 4.72 (1.72–11.99) years. Among the six controls, 50% (n = 3) were boys and 50% (n = 3) were girls and the median age was 5.24 (1.53–13.17) years. The expression level of METTL3 and METTL14 in E/R‐positive ALL patients were lower than in controls (p
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- 2019
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15. Role of cytarabine in paediatric acute promyelocytic leukemia treated with the combination of all-trans retinoic acid and arsenic trioxide: a randomized controlled trial
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Li Zhang, Yao Zou, Yumei Chen, Ye Guo, Wenyu Yang, Xiaojuan Chen, Shuchun Wang, Xiaoming Liu, Min Ruan, Jiayuan Zhang, Tianfeng Liu, Fang Liu, Benquan Qi, Wenbin An, Yuanyuan Ren, Lixian Chang, and Xiaofan Zhu
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Acute promyelocytic leukaemia ,All-trans retinoic acid ,Arsenic trioxide ,Paediatric ,Cytarabine ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested to be safe and effective for adult acute promyelocytic leukaemia (APL). As of 2010, the role of cytarabine (Ara-C) in APL was controversial. The aim of this study was to test the efficacy and safety of ATRA and ATO in paediatric APL patients. Also, we assessed whether Ara-C could be omitted in ATO and ATRA- based trials in children. Methods We performed a randomized controlled trial in paediatric APL patients (≤14 years of age) in our hospital from May 2010 to December 2016. All of the patients were assigned to receive ATRA plus ATO for induction followed by one course of idarubicin (IDA) and ATO (28 days). The patients were then randomly assigned to receive two courses of daunorubicin (DNR, no- Ara-C group) or DNR + Ara-C (Ara-C group). All of the patients were followed with maintenance therapy with oral ATRA, 6-mercaptopurine, and methotrexate for 1.5 years. Results Among the 66 patients, 43 were male and 23 were female. All of the patients achieved complete remission (CR) with the exception of one who gave up the treatment. During induction therapy, all toxicity events were reversed after appropriate management. Thirty patients in the Ara-C group underwent 57 courses of treatment, and 35 patients in the no-Ara-C group underwent 73 courses of treatment. No significant differences in age, genders, white blood cell counts, haemoglobin levels, and platelet counts were found between the Ara-C and no-Ara-c groups. Greater myelosuppression and sepsis were observed in the Ara-C group during the consolidation courses. No patient died at consolidation, and only one patient relapsed. No differences were found in event-free survival, disease-free survival and overall survival between the two groups. Additionally, our analysis of the arsenic levels in the plasma, urine, hair and nails of the patients indicated that no significant accumulation of arsenic occurred after ATO was discontinued for 12 months. Conclusions Overall, ATO and ATRA are safe and effective for paediatric APL patients and Ara-C could be omitted when ATO is used for two courses. Trial registration ClinicalTrials.gov (NCT01191541, retrospectively registered on 18 August 2010).
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- 2018
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16. Phenotypic and genotypic correlation evaluation of 148 pediatric patients with Fanconi anemia in a Chinese rare disease cohort
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Lixian, Chang, Li, Zhang, Wenbin, An, Yang, Wan, Yuli, Cai, Yang, Lan, Aoli, Zhang, Lipeng, Liu, Min, Ruan, Xiaoming, Liu, Ye, Guo, Wenyu, Yang, Xiaojuan, Chen, Yumei, Chen, Shuchun, Wang, Yao, Zou, Weiping, Yuan, and Xiaofan, Zhu
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Biochemistry (medical) ,Clinical Biochemistry ,General Medicine ,Biochemistry - Abstract
Fanconi anemia (FA) is a rare autosomal recessive, X-linked or autosomal dominant disease. Few large-scale FA investigations of rare disease cohorts have been conducted in China.We enrolled 148 patients diagnosed with FA according to evidence from the clinical phenotype, family history, and a set of laboratory tests. Next, the clinical manifestations and correlation between the genotype and phenotype of FA pediatric cases were investigated.The most common FA subtype in our cohort was FA-A (51.4 %), followed by FA-D2 and FA-P. Finger (26 %) and skin (25 %) deformities were the most common malformations. Based on family history, blood system diseases (51 %) had the highest incidence rate, followed by digestive system tumours. A set of new or prognosis-related mutation sites was identified. For example, c.2941 T G was a new most common missense mutation site for FANCA. FANCP gene mutation sites were mainly concentrated in exons 12/14/15. The mutations of FANCI/FANCD2 were mainly located at the α helix and β corners of the protein complex. FA-A/D1 patients with splicing or deletion mutations showed more severe disease than those with missense mutations. Chromosome 1/3/7/8 abnormalities were closely linked to the progression of FA to leukemia.Our study investigated the clinical features and genotype/phenotype correlation of 148 Chinese pediatric FA patients, providing new insight into FA.
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- 2023
17. Short-term efficacy of decitabine-based therapy in JMML: a retrospective study from a single center in China
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Yuli Cai, Jingliao Zhang, Meihui Yi, Wenfeng Zhang, Xiaoming Liu, Xiaoyan Zhang, Yang Wan, Lixian Chang, Li Zhang, Xiaojuan Chen, Ye Guo, Yao Zou, Yumei Chen, Jun Li, Yingchi Zhang, Wenyu Yang, and Xiaofan Zhu
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Leukemia, Myelomonocytic, Juvenile ,Hematopoietic Stem Cell Transplantation ,Humans ,Hematology ,Child ,Decitabine ,Progression-Free Survival ,Retrospective Studies - Abstract
Juvenile myelomonocytic leukemia (JMML) is an aggressive pediatric myeloproliferative disease, and newly diagnosed patients frequently cannot tolerate hematopoietic stem cell transplantation (HSCT) at diagnosis due to their poor condition. This retrospective analysis aimed to explore the short-term effect of decitabine-dominant therapy on improving the condition of JMML patients before HSCT. The subjects were 10 JMML patients. All patients were treated with decitabine after low-dose chemotherapy with an interval of 4 weeks before bridging to HSCT. The median treatment course was 3 cycles, and the overall response rate (ORR) was 70.0% after one cycle and 71.4% after three cycles. White blood cell (WBC) and monocyte counts were significantly lower after treatment, and spleen volume was also lower, though not significantly lower. The 12 month progression-free survival rate (PFS) was 80.0 ± 12.6%. Decitabine-dominant therapy was beneficial for reducing tumor burden and improving clinical condition.
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- 2022
18. Single-cell analysis highlights a population of Th17-polarized CD4+ naïve T cells showing IL6/JAK3/STAT3 activation in pediatric severe aplastic anemia
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Jingliao Zhang, Tianfeng Liu, Yongjuan Duan, Yanxia Chang, Lixian Chang, Chao Liu, Xiaoyan Chen, Xuelian Cheng, Tianyu Li, Wenyu Yang, Xiaojuan Chen, Ye Guo, Yumei Chen, Yao Zou, Li Zhang, Xiaofan Zhu, and Yingchi Zhang
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Immunology ,Immunology and Allergy - Published
- 2023
19. Long-term outcomes of 172 children with severe aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine
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Lixian Chang, Li-Peng Liu, Ye Guo, Meihui Yi, Yuanyuan Ren, Aoli Zhang, Chao Liu, Jing Feng, Shu-Chun Wang, Yang Lan, Yuli Cai, Xiaofan Zhu, Jingliao Zhang, and Xiao-Yan Chen
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Male ,medicine.medical_specialty ,Time Factors ,Multivariate analysis ,Adolescent ,Severity of Illness Index ,Peripheral blood mononuclear cell ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Long term outcomes ,Animals ,Humans ,Medicine ,Rabbit ATG ,Child ,Antilymphocyte Serum ,Retrospective Studies ,Hematology ,business.industry ,Anemia, Aplastic ,Infant ,General Medicine ,Severe Aplastic Anemia ,Survival Rate ,Rabbit antithymocyte globulin ,Treatment Outcome ,medicine.anatomical_structure ,Child, Preschool ,030220 oncology & carcinogenesis ,Cyclosporine ,Female ,Rabbits ,Bone marrow ,business ,Immunosuppressive Agents ,Follow-Up Studies ,030215 immunology - Abstract
This study retrospectively analyzed the clinical outcome of 172 children with newly diagnosed severe aplastic anemia (SAA) between January 2008 and April 2018, who received rabbit antithymocyte globulin (ATG) and cyclosporine (CsA) as first-line treatment. The median age at diagnosis was 5 years (range, 1–14). The overall response rates were 22.7%, 45.3%, and 61% at 40 days, 3 months, and 6 months, respectively, after rabbit ATG. In multivariate analysis, mild disease severity was the only predictor of favorable response at 6 months (P = 0.006). In the present study, median follow-up period was 63 months (range, 1–135). The 5-year overall survival (OS) and failure-free survival (FFS) rates were 90.5% and 70.4%. Multivariate analysis showed that erythroid burst-forming units (BFU-E) > 2/105 bone marrow mononuclear cell (BMMNC) (P = 0.037) and time interval before IST ≤ 30 days (P = 0.017) were independent positive predictors for OS, meanwhile BFU-E > 2/105BMMNC (P = 0.029) was the only favorable prognostic factor for FFS.
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- 2020
20. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients.
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Lixian Chang, Xuelian Cheng, Yao Zou, Weiping Yuan, Li Zhang, and Xiaofan Zhu
- Abstract
Considering the connection between the Fanconi anemia (FA) signaling pathway and tumor development, we aim to investigate the links between the FA gene expression and the survival prognosis of acute myeloid leukemia (AML) patients. Our study begins by identifying two distinct clusters of pediatric AML patients. Following the batch matching of the TARGET-AML, TCGA-LAML GSE71014, GSE12417, and GSE37642 cohorts, the samples were divided into a training set and an internal validation set. A Lasso regression modeling analysis was performed to identify five signatures: BRIP1, FANCC, FANCL, MAD2L2, and RFWD3. The AML samples were stratified into high- and low-risk groups by evaluating the risk scores. The AML high-risk patients showed a poorer overall survival prognosis. To predict the survival rates, we developed an FA Nomogram incorporating risk score, gender, age, and French–American–British classification. We further utilized the BEAT-AML cohort for the external validation of FA-associated prognostic models and observed good clinical validity. Additionally, we found a correlation between DNA repair, cell cycle, and peroxide-related metabolic events and FA-related high/low risk or cluster 1/2. In summary, our novel FA-associated prognostic models promise to enhance the prediction of pediatric AML prognosis. [ABSTRACT FROM AUTHOR]
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- 2023
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21. Targeted Next-Generation Sequencing of Circulating Tumor DNA, Bone Marrow, and Peripheral Blood Mononuclear Cells in Pediatric AML
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Xiaojuan Chen, Ye Guo, Ben-Quan Qi, Shan-Bo Cao, Lixian Chang, Fang Liu, Aoli Zhang, Xiaofan Zhu, Xiao-Yan Chen, Xiao-Ming Liu, Li-Peng Liu, Yumei Chen, Yao Zou, Feng Lou, Yingchi Zhang, Li-Xia Liu, Shu-Chun Wang, Min Ruan, Chengcheng Wang, and Li Zhang
- Subjects
0301 basic medicine ,Cancer Research ,acute myeloid leukemia ,Gene mutation ,medicine.disease_cause ,Peripheral blood mononuclear cell ,DNA sequencing ,03 medical and health sciences ,0302 clinical medicine ,targeted next-generation sequencing ,Medicine ,Clinical significance ,mutation (genetics) ,Allele frequency ,Gene ,RC254-282 ,Original Research ,circulating tumor DNA ,Mutation ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Molecular biology ,pediatric ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Bone marrow ,business - Abstract
BackgroundThe aim of the study was to validate the diagnostic role of circulating tumor DNA (ctDNA) in genetics aberration on the basis of next-generation sequencing (NGS) in pediatric acute myeloid leukemia (AML).MethodsBone marrow (BM) and peripheral blood (PB) were collected from 20 AML children at the time of initial diagnosis, and a ctDNA sample was isolated from PB. Detection of mutation was performed on ctDNA, BM, and peripheral blood mononuclear cell (PBMC) by NGS based on a 185-gene panel.ResultsAmong 185 genes sequenced by the NGS platform, a total of 82 abnormal genes were identified in 20 patients. Among them, 61 genes (74.39%) were detected in ctDNA, PBMC, and BM samples, while 11 (13.41%) genes were found only in ctDNA and 4 (4.88%) were detected only in the BM sample, and 2 (2.44%) were detected only in PBMC. A total of 239 mutations were detected in three samples, while 209 in ctDNA, 180 in bone marrow, and 184 in PBMC. One hundred sixty-four mutations in ctDNA were shared by matched BM samples, and the median variant allelic frequency (VAF) of these mutations was 41.34% (range, 0.55% to 99.96%) and 44.36% (range, 0.56% to 99.98%) in bone marrow and ctDNA. It was found that 65.79% (75/114) of mutations with clinical significance were detected in three samples, with 9 mutations detected both in ctDNA and BM, and 2 mutations detected both in PBMC and BM. The consistency of mutations with clinical significance between ctDNA and BM was 77.06% (84/109). Among the 84 mutations with clinical significance detected in both sources, the concordance of VAF assessment by both methods was high (R2 = 0.895).ConclusionThis study demonstrates that ctDNA was a reliable sample in pediatric AML and can be used for mutation detection. Consistency analysis showed that ctDNA can mirror the genomic information from BM. In addition, a subset of mutations was exclusively detected in ctDNA. These data support the fact that monitoring ctDNA with next-generation sequencing-based assays can provide more information about gene mutations to guide precision treatment in pediatric AML.
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- 2021
22. DNAH2 facilitates the homologous recombination repair of Fanconi anemia pathway through modulating FANCD2 ubiquitination
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Wen-Qi Wu, Xiao-Min Wang, Xiaofan Zhu, Wenbin An, Chao Liu, Lixian Chang, Yingchi Zhang, Aoli Zhang, Yang Wan, Chunmin Huang, Xingjie Gao, Min Gao, Yuxia Wang, and Wei-Ping Yuan
- Subjects
Ubiquitin ,biology ,Fanconi anemia ,hemic and lymphatic diseases ,Automotive Engineering ,FANCD2 ,biology.protein ,medicine ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Homologous recombination ,medicine.disease ,Cell biology - Abstract
Fanconi anemia (FA), an X-linked genetic or autosomal recessive disease, exhibits complicated pathogenesis. Previously, we detected the mutated Dynein Axonemal Heavy Chain 2 (DNAH2) gene in 2 FA cases. Herein, we further investigated the potential association between DNAH2 and the homologous recombination repair pathway of FA. The assays of homologous recombination repair, mitomycin C (MMC) sensitivity, immunofluorescence, and ubiquitination modification were performed in U2OS and DR-U2OS cell lines. In MMC-treated U2OS cells, the downregulation of the DNAH2 gene increased the sensitivity of cells to DNA inter-strand crosslinks. We also observed the reduced enrichment of FANCD2 protein to DNA damage sites. Furthermore, the ubiquitination modification level of FANCD2 was influenced by the deficiency of DNAH2. Thus, our results suggest that DNAH2 may modulate the cell homologous recombination repair partially by increasing the ubiquitination and the enrichment to DNA damage sites of FANCD2. DNAH2 may act as a novel co-pathogenic gene of FA patients.
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- 2021
23. The study of transcriptome sequencing in childhood immune thrombocytopenia
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Xiaofan Zhu, Lixian Chang, Congcong Sun, Yanling Lv, and Jinxia Guan
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Purpura ,business.industry ,Immunology ,Medicine ,Hematology ,General Medicine ,medicine.symptom ,business ,Letter to the Editor ,Immune thrombocytopenia ,Transcriptome Sequencing - Published
- 2019
24. Combination of umbilical cord mesenchymal stem cells and standard immunosuppressive regimen for pediatric patients with severe aplastic anemia
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Yingchi Zhang, Lixian Chang, Fang Liu, Yuli Cai, Jing Feng, Zhongchao Han, Xiaofan Zhu, Zhibo Han, Li-Peng Liu, Meihui Yi, and Yang Lan
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0301 basic medicine ,medicine.medical_specialty ,Severe aplastic anemia ,Umbilical cord ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Statistical significance ,medicine ,Humans ,Prospective Studies ,Aplastic anemia ,Child ,Adverse effect ,Mesenchymal stem cell ,business.industry ,lcsh:RJ1-570 ,Anemia, Aplastic ,lcsh:Pediatrics ,Mesenchymal Stem Cells ,medicine.disease ,Pathophysiology ,Clinical trial ,Immunosuppressive therapy ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Concomitant ,Pediatrics, Perinatology and Child Health ,Cyclosporine ,business ,Research Article - Abstract
Background Defects of bone marrow mesenchymal stem cells (BM-MSCs) in proliferation and differentiation are involved in the pathophysiology of aplastic anemia (AA). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) may improve the efficacy of immunosuppressive therapy (IST) in childhood severe aplastic anemia (SAA). Methods We conducted an investigator-initiated, open-label, and prospective phase IV trial to evaluate the safety and efficacy of combination of allogenic UC-MSCs and standard IST for pediatric patients with newly diagnosed SAA. In mesenchymal stem cells (MSC) group, UC-MSCs were injected intravenously at a dose of 1 × 106/kg per week starting on the 14th day after administration of rabbit antithymocyte globulin (ATG), for a total of 3 weeks. The clinical outcomes and adverse events of patients with UC-MSCs infusion were assessed when compared with a concurrent control group in which patients received standard IST alone. Results Nine patients with a median age of 4 years were enrolled as the group with MSC, while the data of another 9 childhood SAA were analysed as the controls. Four (44%) patients in MSC group developed anaphylactic reactions which were associated with rabbit ATG. When compared with the controls, neither the improvement of blood cell counts, nor the change of T-lymphocytes after IST reached statistical significance in MSC group (both p > 0.05) and there were one (11%) patient in MSC group and two (22%) patients in the controls achieved partial response (PR) at 90 days after IST. After a median follow-up of 48 months, there was no clone evolution occurring in both groups. The 4-year estimated overall survival (OS) rate in two groups were both 88.9% ± 10.5%, while the 4-year estimated failure-free survival (FFS) rate in MSC group was lower than that in the controls (38.1% ± 17.2% vs. 66.7% ± 15.7%, p = 0.153). Conclusions Concomitant use of IST and UC-MSCs in SAA children is safe but may not necessarily improve the early response rate and long-term outcomes. This clinical trial was registered at ClinicalTrials.gov, identifier: NCT02218437 (registered October 2013).
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- 2021
25. Low absolute neutrophil count during induction therapy is an adverse prognostic factor in childhood acute lymphoblastic leukaemia
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Yumei Chen, Wen-Qi Wu, Min Ruan, Wenyu Yang, Meihui Yi, Li Zhang, Chao Liu, Lixian Chang, Yingchi Zhang, Xiaojuan Chen, Lu-Yang Zhang, Aoli Zhang, Li-Peng Liu, Yao Zou, Ye Guo, Xiaofan Zhu, Xiao-Yan Chen, and Yang Lan
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Male ,medicine.medical_specialty ,Neoplasm, Residual ,Neutrophils ,medicine.medical_treatment ,Lymphocyte ,Gastroenterology ,Disease-Free Survival ,Blood cell ,Leukocyte Count ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Lymphocyte Count ,Risk factor ,Child ,Retrospective Studies ,Chemotherapy ,Hematology ,business.industry ,Retrospective cohort study ,Induction Chemotherapy ,General Medicine ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Prognosis ,Regimen ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Absolute neutrophil count ,Female ,business ,030215 immunology - Abstract
Variation in normal blood cells during chemotherapy has not been recognised as a risk factor guiding chemotherapy in childhood acute lymphoblastic leukaemia (ALL). This study aims to explore whether variations in normal haematopoiesis determine prognosis as well as to improve risk-stratified treatment in childhood ALL. A retrospective study of 279 cases of ALL treated with the CCCG-ALL-2015 regimen in the Division of Pediatric Blood Diseases Center, Institute of HematologyBlood Diseases Hospital, Chinese Academy of Medical SciencesPeking Union Medical College, from May 2015 to January 2017 was performed to analyse the prognostic impact of blood cell levels on day 19 of induction therapy by Kaplan-Meier method. Patients with childhood ALL with absolute neutrophil count (ANC) ≤ 90 cells/μl, absolute monocyte count (AMC) ≤ 10 cells/μl or absolute lymphocyte count (ALC) ≤ 1000 cells/μl on day 19 of induction therapy had a lower event-free survival (EFS) rate than those with higher values (all P0.05). Multivariate analysis confirmed that ANC ≤ 90 cells/μl and ALC ≤ 1000 cells/μl were independent adverse prognostic factors (HR = 1.981 and 2.162, respectively, both P0.05). Among patients with minimal residual disease (MRD)1% on day 19 of induction therapy, those with ANC ≤ 90 cells/μl had lower EFS than those with ANC90 cells/μl (70.8 ± 6.1% vs 86.4 ± 3.1%, P = 0.001). In the subgroup with the BCR/ABL1 fusion gene, patients with ANC ≤ 90 cells/μl on day 19 of induction therapy also had lower EFS than those with ANC90 cells/μl (34.4 ± 25.2% vs 25.0 ± 21.7%, P = 0.041). ANC and ALC during induction therapy are independent prognostic factors for childhood ALL. ANC contributes to guiding the prognosis of patients with low-level MRD or the BCR/ABL1 fusion gene.
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- 2021
26. Pediatric Acute Lymphoblastic Leukemia Patients Exhibit Distinctive Alterations in the Gut Microbiota
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Ye Guo, Xiaojuan Chen, Hongrui He, Wenyu Yang, Min Ruan, Yingchi Zhang, Yumei Chen, Li Zhang, Lixian Chang, Shu-Chun Wang, Kejian Wang, Xiaofan Zhu, Xiao-Ming Liu, Yu Gan, and Yao Zou
- Subjects
Microbiology (medical) ,Immunology ,interleukin-10 ,lcsh:QR1-502 ,Gut flora ,Microbiology ,lcsh:Microbiology ,Pathogenesis ,Immune system ,Cellular and Infection Microbiology ,acute lymphoblastic leukemia (ALL) ,RNA, Ribosomal, 16S ,Humans ,Child ,Childhood Acute Lymphoblastic Leukemia ,Feces ,Original Research ,Clostridiales ,biology ,gut microbiota ,Edwardsiella tarda ,16S rRNA quantitative microarray ,Fusobacterium ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,biology.organism_classification ,Gastrointestinal Microbiome ,Infectious Diseases ,Fusobacterium naviforme ,quantitative PCR ,Etiology - Abstract
Previous studies have shown that gut microbiota can affect human immune system in many ways. Our aim was to investigate quantitative differences in fecal bacterial compositions of childhood acute lymphoblastic leukemia (ALL) patients compared to those of healthy children, so as to identify individual bacterial species that are related to the etiology of ALL. We recruited 81 subjects, including 58 patients with ALL and 23 healthy controls. Fecal samples were collected and examined by 16S rRNA quantitative arrays and bioinformatics analysis. Both Principal Coordinates Analysis (PCoA) and Non-metric Multidimensional scaling (NMDS) demonstrated that the microbial composition of ALL patients deviated from the tight cluster of healthy controls. Multiple bacterial species exhibited significant changes (e.g., Roseburia faecis, Edwardsiella tarda, and Fusobacterium naviforme) in the ALL samples. Some of the differentially abundant taxa were correlated with the level of interleukin-10. The ALL cases could be efficiently distinguished from healthy controls by the random forest model based on differential species (area under ROC curve = 0.843). Taken together, the composition of gut microbiota differed from healthy controls to pediatric ALL patients. Our study identified a series of ALL-related species in the gut microbiota, providing a new direction for future studies aiming to understand the host-gut microbiota interplay in ALL pathogenesis.
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- 2020
27. Successful Treatment of a 19-Month-Old Boy with Hepatitis Associated Aplastic Anemia by Infusion of Umbilical Cord-Derived Mesenchymal Stromal Cells: A Case Report
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Fang, Liu, primary, Meikuang, Lim, additional, Ye, Guo, additional, Xiaojuan, Chen, additional, Wenyu, Yang, additional, Min, Ruan, additional, Lixian, Chang, additional, Weiqiang, Wang, additional, Zhibo, Han, additional, Zhongchao, Han, additional, and Xiaofan, Zhu, additional
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- 2021
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28. Venous Thromboembolism After Peripherally Inserted Central Catheters Placement in Children With Acute Leukemia: A Single-center Retrospective Cohort Study
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Xiaoyan Zhang, Lixian Chang, Hui-Min Zhang, Xiaofan Zhu, Yang Wan, Yuanyuan Ren, and Beibei Zhao
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Male ,medicine.medical_specialty ,Catheterization, Central Venous ,China ,Adolescent ,Single Center ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,hemic and lymphatic diseases ,Catheterization, Peripheral ,Medicine ,Humans ,Cerebral venous sinus thrombosis ,Child ,Retrospective Studies ,Acute leukemia ,business.industry ,Infant ,Retrospective cohort study ,Hematology ,Venous Thromboembolism ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Prognosis ,Thrombosis ,Surgery ,Pulmonary embolism ,Venous thrombosis ,Leukemia ,Leukemia, Myeloid, Acute ,Oncology ,030220 oncology & carcinogenesis ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,business ,030215 immunology ,Follow-Up Studies - Abstract
Objective To explore the incidence rate and characteristics of symptomatic venous thromboembolism (VTE) after peripherally inserted central catheters (PICC) placement in children with acute leukemia (AL). Methods The authors performed a retrospective study aiming at children admitted to Pediatric Blood Diseases Center with a new diagnosis of AL and received a PICC insertion, collected the clinical materials of all venous thrombosis cases, and analyzed the incidence rate and characteristics in various types of AL. Results From September 2007 to December 2018, a total of 2423 patients got PICCs at least once, of whom 29 patients experienced thrombosis events and the overall incidence rate of symptomatic VTE after PICC insertion was 1.2%. Deep venous thrombosis accounted for the majority with 75.9%. Seven cases of cerebral venous sinus thrombosis were documented and they all developed in patients with acute lymphoblastic leukemia (ALL). No pulmonary embolism was detected. Patients with acute myeloid leukemia (AML) had an identical risk of thrombosis to patients with acute lymphoblastic leukemia (ALL) (1.7% vs. 1.09%, P>0.05). All thrombi in patients with AML were located on the upper extremity, whereas in the ALL group about half of the thromboembolism developed in other locations. There were no statistical differences between patients in different clinical trials of the ALL group (0.7% vs. 1.6%, P>0.05). Conclusions The incidence rates of symptomatic VTE after PICC placement in children with AL in our center were relatively low and acceptable. For patients with AML, PICC placement plays the most important role in venous thrombosis. However, in patients with ALL, the potential risk factors were more complex.
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- 2020
29. Long-Term Outcome Prediction After Immunosuppressive Therapy for Severe Aplastic Anemia in Childhood by Machine Learning Methods
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Yong Ma, Jingliao Zhang, Mingchen Yan, Yuli Cai, Binghang Liu, Meihui Yi, Xiaofan Zhu, Lixian Chang, Zhenyu Li, Li Zhang, Jian Wang, Yang Wan, Yang Lan, Aoli Zhang, Li-Peng Liu, Haihui Zheng, Ye Guo, Yingrui Li, Shu-Chun Wang, Yuanyuan Ren, and Jing Feng
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medicine.medical_specialty ,Hematology ,medicine.diagnostic_test ,business.industry ,Bone Marrow Smear ,Medical record ,Disease ,Machine learning ,computer.software_genre ,Bone marrow examination ,medicine.anatomical_structure ,White blood cell ,Internal medicine ,Medicine ,Bone marrow ,Artificial intelligence ,Stage (cooking) ,business ,computer - Abstract
Background: Severe Aplastic Anemia (SAA) in children is a rare severe disease, and the prognosis after immunosuppressive therapy (IST) is heterogeneous. Few models could accurately predict the long-term outcomes of immunosuppressive therapy for children SAA patients. Previous researches mainly focused on a few pretreatment factors,because SAA patients need to test the bone marrow at 3, 6, 9, and 12 months after IST treatment, and response-based surrogates of outcome have been shown to be highly predictive in other diseases. Based on these, we collected clinical electronic medical records (EMR) from 203 children with SAA, including comprehensive clinical tests from blood routine to bone marrow examination throughout the entire treatment process, to establish a model with more effective prognostic factors to predict the prognosis of patients. Our study will provides a novel and more effective prognosis time node for reducing the times of bone marrow puncture and to guide the next treatment. Methods: Based on the machine learning methods, we established a model with the AUC 0.962 to predict the long-term outcomes in the early stage of SAA patients with IST. Findings: By analyzing the indicators related to long-term efficacy, we found that some of the indicators such as white blood cell count, lymphocyte count and absolute reticulocyte count (ARC) which are consistent with previous studies; but the age is not a suitable predictor for children with SAA, the lymphocyte ratio of bone marrow smear is more effective than lymphocyte count in blood, the C-reactive protein, level of vitamin B12, IL-6 and IL-8 in the early stage of the disease is highly correlated with long-term efficacy (P
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- 2020
30. Analysis of pathological changes and related factors in liver tissue of HBeAg-negative patients with low HBsAg levels
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Huimin Li, Junyi Li, Lixian Chang, Hui Wang, Yingrong Du, Jie Chen, Li Liu, and Chunyun Liu
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0301 basic medicine ,Adult ,Liver Cirrhosis ,Male ,HBsAg ,medicine.medical_specialty ,Time Factors ,Adolescent ,Spleen ,Gastroenterology ,Antiviral Agents ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Hepatitis B, Chronic ,Fibrosis ,Internal medicine ,medicine ,Humans ,Hepatitis B e Antigens ,Vein ,Pathological ,Retrospective Studies ,Hematology ,Hepatitis B Surface Antigens ,business.industry ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Logistic Models ,Liver ,Splenic vein ,030220 oncology & carcinogenesis ,Female ,business - Abstract
The relationship between pathological changes in liver tissue and the level of hepatitis B surface antigen (HBsAg) remains unclear. This study aimed to analyze the pathological changes in liver tissue and its related factors in patients with low-level HBsAg in order to provide a basis for judging the condition of these patients. A retrospective study was performed on 96 chronic hepatitis B patients with HBsAg levels 1400 IU/ml and 0.05 IU/ml. The histopathological examination of these patients was conducted. Univariate and multivariate analyses were used to determine risk factors for pathological changes. Among the 96 patients, 57.3% (55) had inflammatory events ≥ G2 and 33.4% (33) had fibrosis ≥ S2. HBV infection duration (p = 0.001) and splenic vein diameter (p = 0.001) were independent risk factors of liver inflammation (≥ G2) in patients with low-level HBsAg, while AST (p = 0.006) and PLT (p = 0.005) were independent risk factors of liver fibrosis (≥ S2). Moreover, HBV infection duration (p 0.001) and spleen vein (p = 0.001) were independent factors of potential antiviral treatment. Liver inflammation and fibrosis are still common in patients with low-level HBsAg; thus, the monitoring and appropriate antiviral treatment cannot be ignored.
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- 2019
31. Correlation Analysis of DNA Methylation Level and Clinical Characteristics in JMML Patients
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Wenyu Yang, Xiaofan Zhu, Yao Zou, Yumei Chen, Xiaojuan Chen, Xiaoyan Zhang, Yang Wan, Yingchi Zhang, Jingliao Zhang, Meihui Yi, Xiao-Ming Liu, Ye Guo, Lixian Chang, Li Zhang, and Yuli Cai
- Subjects
Immunology ,DNA methylation ,Correlation analysis ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Molecular biology - Abstract
Objective: As a rare, aggressive pediatric myeloproliferative disease, juvenile myelomonocytic leukemia (JMML) encompassed both biological features of myelodysplastic syndrome and myeloproliferative neoplasm. Studies have shown that the methylation level in JMML patients is closely related to prognosis, and patients with high methylation level have poor prognosis. This study aimed to find clinical indicators that were associated with different methylation levels and prognosis. Methods: The clinical information of 24 JMML patients with DNA samples admitted to our center from December 2013 to May 2020 was retrospectively analyzed, and the DNA methylation level of their whole genome was detected. Results: The median age of onset was 14.5 months (0.1-153 months) among the 24 cases, including 17 males and 7 females. At diagnosis, the median WBC count was 27.1×10 9/L (6.2-98.1×10 9/L), and the median platelet count was 38×10 9/L (10-277×10 9/L). Chromosome karyotype abnormalities were found in 12.5% (3/24) of patients. Next-generation sequencing results showed that 79.2% (19/24) patients had at least one Ras pathway-related classical gene mutation, and 41.7% (10/24) patients had two or more somatic mutations. Genomic DNA methylation levels were divided into three groups: 10 cases in the hypomethylation group, 4 cases in the moderate methylation group, and 10 cases in the hypermethylation group. There were significant differences in age, platelets, PTPN11 gene mutation and the number of somatic mutations ≥2 in different methylation groups (P Conclusions: JMML patients with high methylation level in the DNA genome at diagnosis were older and with lower platelet levels, and hypermethylation were significantly correlated with high-risk prognostic factors such as PTPN11 gene mutation and ≥2 somatic mutations. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Decitabine for treatment of children with JMML
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- 2021
32. Pathogenesis of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia and mechanisms underlying its relapse
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Xiaofan Zhu, Lixian Chang, and Congcong Sun
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0301 basic medicine ,medicine.medical_specialty ,DNA Copy Number Variations ,Oncogene Proteins, Fusion ,Review ,Pathogenesis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Etv6 runx1 ,Internal medicine ,medicine ,Humans ,Child ,Childhood Acute Lymphoblastic Leukemia ,ETV6/RUNX1 ,relapse ,mechanisms ,Hematology ,business.industry ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,initiation ,ETV6 ,Leukemia ,030104 developmental biology ,Oncology ,RUNX1 ,chemistry ,030220 oncology & carcinogenesis ,childhood acute lymphoblastic leukemia ,Immunology ,Core Binding Factor Alpha 2 Subunit ,Blood disease ,Neoplasm Recurrence, Local ,business - Abstract
// Congcong Sun 1 , Lixian Chang 1 and Xiaofan Zhu 1 1 Center for Pediatric Blood Disease, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, Tianjin, P.R. China Correspondence to: Xiaofan Zhu, email: // Keywords : ETV6/RUNX1, childhood acute lymphoblastic leukemia, mechanisms, initiation, relapse Received : November 21, 2016 Accepted : February 23, 2017 Published : March 18, 2017 Abstract ETV6/RUNX1 ( E/R ) is the most common fusion gene in childhood acute lymphoblastic leukemia (ALL). Multiple lines of evidence imply a “two-hit” model for the molecular pathogenesis of E/R -positive ALL, whereby E/R rearrangement is followed by a series of secondary mutations that trigger overt leukemia. The cellular framework in which E/R arises and the maintenance of a pre-leukemic condition by E/R are fundamental to the mechanism that underlies leukemogenesis. Accordingly, a variety of studies have focused on the relationship between the clones giving rise to the primary and recurrent E/R -positive ALL. We review here the most recent insights into the pathogenic mechanisms underlying E/R -positive ALL, as well as the molecular abnormalities prevailing at relapse.
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- 2017
33. Predicting response to porcine antilymphocyte globulin plus cyclosporine A in children with acquired severe aplastic anemia
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Wenyu Yang, Xiaojuan Chen, Xiaofan Zhu, Li Zhang, Ye Guo, Yumei Chen, Kang Zhou, Yao Zou, Li-Peng Liu, Fengkui Zhang, Xia Chen, Tianfeng Liu, Meihui Yi, Lixian Chang, Fang Liu, and Min Ruan
- Subjects
Male ,medicine.medical_specialty ,Reticulocytes ,Globulin ,Adolescent ,Anemia ,Swine ,Cell Count ,Gastroenterology ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,030225 pediatrics ,Internal medicine ,Medicine ,Animals ,Humans ,Platelet ,Child ,Antilymphocyte Serum ,Response rate (survey) ,Predictive marker ,biology ,business.industry ,Anemia, Aplastic ,Infant ,medicine.disease ,Prognosis ,Severe Aplastic Anemia ,Treatment Outcome ,Predictive value of tests ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Cohort ,biology.protein ,Cyclosporine ,Female ,business ,030217 neurology & neurosurgery ,Immunosuppressive Agents - Abstract
In severe aplastic anemia (SAA), predictive markers of response to immunosuppressive therapy (IST) of porcine antilymphocyte globulin (pALG) have not been well defined. We investigated whether clinical and laboratory findings before treatment could predict response in a pediatric cohort. In this study, we included 70 newly diagnosed SAA children and treated them with pALG. The response rate was documented during follow-up. The log-rank test compared response rates between the potential predictive factors. The response rate was 57.1% at 24 months follow-up. In log-rank test, mild disease severity was the most significant predictive marker of better response (P
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- 2019
34. The study of METTL3 and METTL14 expressions in childhood ETV6/RUNX1-positive acute lymphoblastic leukemia
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Xiaofan Zhu, Congcong Sun, Lixian Chang, Xiao-Yan Chen, and Chao Liu
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0301 basic medicine ,Male ,medicine.medical_specialty ,lcsh:QH426-470 ,Oncogene Proteins, Fusion ,Mrna expression ,Treatment intensification ,Lymphoblastic Leukemia ,acute lymphoblastic leukemia ,030105 genetics & heredity ,Pathogenesis ,03 medical and health sciences ,children ,Etv6 runx1 ,Bone Marrow ,Recurrence ,Risk Factors ,Internal medicine ,Statistical significance ,Genetics ,medicine ,Humans ,RNA, Messenger ,Child ,Molecular Biology ,ETV6/RUNX1 ,Genetics (clinical) ,business.industry ,Infant ,Methyltransferases ,Original Articles ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,lcsh:Genetics ,ETV6 ,030104 developmental biology ,Real-time polymerase chain reaction ,Child, Preschool ,Core Binding Factor Alpha 2 Subunit ,METTL3 ,Female ,Original Article ,METTL14 ,business - Abstract
Background This study was aimed to explore the METTL3 and METTL14 expressions in children with ETV6/RUNX1(E/R)‐positive acute lymphoblastic leukemia (ALL) and investigate the relation between the METTL3 and METTL14 expressions with clinical features. Methods Thirty‐seven newly diagnosed E/R‐positive ALL children and six controls were included in this study. Real‐time quantitative polymerase chain reaction (RT‐PCR) was used to detect the mRNA expression level of METTL3 and METTL14. Results Among the 37 cases, 51.35% (n = 19) were boys and 48.65% (n = 18) were girls and the median age was 4.72 (1.72–11.99) years. Among the six controls, 50% (n = 3) were boys and 50% (n = 3) were girls and the median age was 5.24 (1.53–13.17) years. The expression level of METTL3 and METTL14 in E/R‐positive ALL patients were lower than in controls (p
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- 2019
35. Analysis of the Short-Term Efficacy of Decitabine Combined with Low-Dose Cytarabine in the Treatment of JMML
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Yao Zou, Wenyu Yang, Meihui Yi, Lixian Chang, Weiru Liang, Fang Liu, Yuli Cai, Ye Guo, Yumei Chen, Xiaoyan Zhang, and Xiaofan Zhu
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Oncology ,medicine.medical_specialty ,Chemotherapy ,Juvenile myelomonocytic leukemia ,business.industry ,medicine.medical_treatment ,Immunology ,Decitabine ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Transplantation ,Internal medicine ,medicine ,Cytarabine ,business ,Survival rate ,Myeloproliferative neoplasm ,medicine.drug - Abstract
Objective: Juvenile myelomonocytic leukemia (JMML) has both the disease characteristics of myelodysplastic syndrome and myeloproliferative neoplasm. Currently, hematopoietic stem cell transplantation (HSCT) is the only possible cure. Most of the newly diagnosed pediatric patients with JMML have high tumor burden, rapid disease progression, and may not tolerate HSCT. This study explored the short-term efficacy of decitabine combined with low-dose chemotherapy in the treatment of JMML before transplantation. Methods: A retrospective analysis of the patient files of 9 cases of JMML was performed from January 2019 to May 2020. All patients were given decitabine 20mg/m2× 5 days, supplemented with a small dose of cytarabine (50-100mg/m2×3~5 days), and/or etoposide (50mg/m2×3~5 days) chemotherapy. Each treatment interval is 3~4 weeks, bridging with HSCT after 3~4 treatment courses. Results: The median age of onset of 9 cases of JMML was 2 years old (0.5~4 y), male to female ratio was 8:1, the median size of spleen was 6.4cm (2.9~9.8cm) under the costal arch, and WBC was 28.03×109/L (7.3~127.69×109/L), monocytes were 9.25×109/L (1.66~15.79×109/L) at diagnosis. There were 8 cases in the high-risk group and 1 case in the low-risk group. Second-generation sequencing results show that 7 cases carried PTPN11 somatic mutations. Five in 9 cases had two kinds of classic JMML mutations, and 1 case had only NRAS mutation. Seven patients had normal chromosomal karyotypes, and 3 patients had abnormal 8, 11, and 18 chromosomes, respectively. Median treatment courses with decitabine are 3 courses (1~5 courses), the response rate of one course is 77.8% (7/9), the response rate of three courses is 80% (4/5), one case from high-risk group achieved complete remission after treated with 4 courses of decitabine and low-dose chemotherapy. The five-month progression-free survival rate was 77.8% (7/9). Conclusion: Treating JMML with decitabine combined with low-dose chemotherapy, can reduce patients' tumor burden, improve the general condition, and obtain approximately 80% clinical response rate. Decitabine combined with low-dose chemotherapy can be used as a treatment option for JMML before HSCT. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Safety and effecacy of decitabine applicated in JMML patients have not been confirmed.
- Published
- 2020
36. A single-center, open-label clinical study to evaluate pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte stimulating factor in pediatric patients with acute lymphoblastic leukemia
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Xiaojuan Chen, Li Zhang, Ben-Quan Qi, Lixian Chang, Xiao-Ming Liu, Fang Liu, Xiaofan Zhu, Yumei Chen, Yao Zou, Min Ruan, Wenyu Yang, Ting Li, Ye Guo, and Tian-Feng Liu
- Subjects
Cancer Research ,business.industry ,Lymphoblastic Leukemia ,fungi ,Pharmacology ,Granulocyte ,Single Center ,law.invention ,Granulocyte colony-stimulating factor ,Clinical study ,medicine.anatomical_structure ,Oncology ,Pharmacokinetics ,law ,Recombinant DNA ,Medicine ,Open label ,business - Abstract
e22501 Background: The aims of the study were to investigate the pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony stimulating factor(PEG-rhG-CSF) in pediatric patients with acute lymphoblastic leukemia(ALL), and compare the efficacy and safety of PEG-rhG-CSF (brand name:jinyouli) and rhG-CSF. Methods: Pediatric patients with newly diagnosed ALL who planned to use CAM (cyclophosphamide, cytarabine, 6-mercaptopurine) for chemotherapy were assigned to PEG-rhG-CSF group or rhG-CSF group. In the PEG-rhG-CSF group, PEG-rhG-CSF (100ug/kg) was injected subcutaneously once 48 hours after chemotherapy. In the rhG-CSF group, rhG-CSF (150ug/d) was injected subcutaneously daily from 48 hours after chemotherapy until the absolute neutrophil count (ANC) was≥1.0×109/L. The serum concentration of PEG-rhG-CSF was detected by enzyme-linked immunosorbent assay (ELISA). Safety and efficacy of the two groups were evaluated. Results: Between November 2015 to April 2016, 17 pediatric patients were assigned to PEG-rhG-CSF(n = 9) or rhG-CSF(n = 8) groups. The main pharmacokinetic parameters (mean±SD) of PEG-rhG-CSF group were as follows: Cmax was 353.50±136.3 ng/ml, Tmax was 44.00±20.8 h, t1/2 was 14.58± 2.2h. The PEG-rhG-CSF serum concentration and ANC curve were consistent with the mechanism of neutrophil mediated clearance. The average value of ANC nadir in PEG-rhG-CSF group was 0.18 (±0.32)×109/L, and the rhG-CSF group was 0.08 (±0.09)×109/L, there was no significant difference between the two groups ( P = 0.469). Compared with rhG-CSF, the average time of ANC recovery in PEG-rhG-CSF group was earlier (18.33±2.18 vs. 21.50±2.33, P = 0.021). There were no significant differences in the incidence of FN and infection, the duration of grade Ⅳ neutropenia and hospitalization, and the safety of the two groups. Conclusions: PEG-rhG-CSF had favorable efficacy in pediatric patients with ALL receiving chemotherapy, and there was no serious adverse event. Compared with rhG-CSF, PEG-rhG-CSF needed only once in each chemotherapy cycle, which is more suitable for pediatric patients. Clinical trial information: NCT02953730.
- Published
- 2020
37. Role of cytarabine in paediatric acute promyelocytic leukemia treated with the combination of all-trans retinoic acid and arsenic trioxide: a randomized controlled trial
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Min Ruan, Xiao-Ming Liu, Wenyu Yang, Xiaofan Zhu, Tianfeng Liu, Lixian Chang, Xiaojuan Chen, Fang Liu, Ben-Quan Qi, Yuanyuan Ren, Wenbin An, Shu-Chun Wang, Li Zhang, Yao Zou, Yumei Chen, Ye Guo, and Jia-Yuan Zhang
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Gastroenterology ,law.invention ,chemistry.chemical_compound ,0302 clinical medicine ,Arsenic Trioxide ,Leukemia, Promyelocytic, Acute ,Maintenance therapy ,Randomized controlled trial ,law ,Antineoplastic Combined Chemotherapy Protocols ,Arsenic trioxide ,Child ,Cytarabine ,Induction Chemotherapy ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Treatment Outcome ,Oncology ,Paediatric ,Child, Preschool ,030220 oncology & carcinogenesis ,Female ,Research Article ,medicine.drug ,Acute promyelocytic leukemia ,medicine.medical_specialty ,Adolescent ,Daunorubicin ,Tretinoin ,lcsh:RC254-282 ,03 medical and health sciences ,Internal medicine ,Genetics ,medicine ,Humans ,Idarubicin ,neoplasms ,All-trans retinoic acid ,business.industry ,medicine.disease ,Acute promyelocytic leukaemia ,Consolidation Chemotherapy ,030104 developmental biology ,chemistry ,Case-Control Studies ,Methotrexate ,business ,Biomarkers - Abstract
Background The combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested to be safe and effective for adult acute promyelocytic leukaemia (APL). As of 2010, the role of cytarabine (Ara-C) in APL was controversial. The aim of this study was to test the efficacy and safety of ATRA and ATO in paediatric APL patients. Also, we assessed whether Ara-C could be omitted in ATO and ATRA- based trials in children. Methods We performed a randomized controlled trial in paediatric APL patients (≤14 years of age) in our hospital from May 2010 to December 2016. All of the patients were assigned to receive ATRA plus ATO for induction followed by one course of idarubicin (IDA) and ATO (28 days). The patients were then randomly assigned to receive two courses of daunorubicin (DNR, no- Ara-C group) or DNR + Ara-C (Ara-C group). All of the patients were followed with maintenance therapy with oral ATRA, 6-mercaptopurine, and methotrexate for 1.5 years. Results Among the 66 patients, 43 were male and 23 were female. All of the patients achieved complete remission (CR) with the exception of one who gave up the treatment. During induction therapy, all toxicity events were reversed after appropriate management. Thirty patients in the Ara-C group underwent 57 courses of treatment, and 35 patients in the no-Ara-C group underwent 73 courses of treatment. No significant differences in age, genders, white blood cell counts, haemoglobin levels, and platelet counts were found between the Ara-C and no-Ara-c groups. Greater myelosuppression and sepsis were observed in the Ara-C group during the consolidation courses. No patient died at consolidation, and only one patient relapsed. No differences were found in event-free survival, disease-free survival and overall survival between the two groups. Additionally, our analysis of the arsenic levels in the plasma, urine, hair and nails of the patients indicated that no significant accumulation of arsenic occurred after ATO was discontinued for 12 months. Conclusions Overall, ATO and ATRA are safe and effective for paediatric APL patients and Ara-C could be omitted when ATO is used for two courses. Trial registration ClinicalTrials.gov (NCT01191541, retrospectively registered on 18 August 2010).
- Published
- 2018
38. [Knocking out of human DNAH2 gene in U2OS cells by CRISPR/Cas9n double nick system]
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Lixian, Chang, Congcong, Sun, Xiaojuan, Chen, Wenyu, Yang, Jiayuan, Zhang, Yingchi, Zhang, Weiping, Yuan, and Xiaofan, Zhu
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Gene Knockout Techniques ,Cell Line, Tumor ,Genetic Vectors ,Humans ,Clustered Regularly Interspaced Short Palindromic Repeats ,Axonemal Dyneins ,Transfection ,Plasmids ,RNA, Guide, Kinetoplastida - Abstract
To study the biological function of DNAH2 (Homo sapiens dynein, axonemal, heavy chain 2) gene, we constructed human stable U2OS cell line of DNAH2 gene knockout through CRISPR/Cas9n double nick system. The A, B sgRNAs (Single guide RNA) and complementary strands were designed and synthesized. The double-stranded structures were formed during annealing, and connected with BbsⅠ cohesive ends-containing pX462 linear vector to construct the recombinant eukaryotic expression plasmids, including pX462-DNAH2-A and pX462-DNAH2-B. After the co-transfection of the two plasmids into U2OS cells, the addition of puromycin and limiting dilution method were used to obtain positive monoclonal cell line. Western blotting assay was then performed to detect the expression of DNAH2 protein, and PCR-sequencing technology was finally utilized to analyze the mutation feature. The results showed that A, B sgRNAs duplex was successfully inserted into pX462 vector, and DNAH2 protein was not expressed and DNAH2 gene suffered from the frame-shift mutation in U2OS-DNAH2-KO monoclonal cell line. These demonstrated that DNAH2 knockout U2OS stable cell line was successfully constructed through CRISPR/Cas9n double nick system, which providing a useful tool for the study of DNAH2 gene.基于CRISPR/Cas9n double nick 技术构建人DNAH2 (Homo sapiens dynein, axonemal, heavy chain 2) 基因敲除的U2OS 稳定细胞株,旨在研究DNAH2 基因的生物学功能。首先设计并合成A、B 两个sgRNA (Single guide RNA) 以及各自的互补链,退火连接形成DNAH2 sgRNA-A、B 双链,再分别与带有BbsⅠ粘性末端的pX462 线性载体相连,形成pX462-DNAH2-A、pX462-DNAH2-B 重组真核表达质粒。质粒共转染至U2OS 细胞后,加入嘌呤霉素,以有限稀释法获得阳性单克隆细胞株,再以蛋白印迹实验检测DNAH2 蛋白的表达,最后通过PCR-基因测序技术分析突变特点。结果显示A、B sgRNA 双链成功插入pX462 载体,U2OS-DNAH2-KO单克隆细胞株中DNAH2 蛋白不表达,DNAH2 基因发生移码突变,从而证实利用CRISPR/Cas9n double nick系统成功构建人DNAH2 基因敲除的U2OS 稳定细胞株,为研究DNAH2 基因提供有利工具。.
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- 2017
39. CALR mutation screening in pediatric primary myelofibrosis
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Wenbin An, Ye Guo, Yang Wan, Peihong Zhang, Xiaofan Zhu, Xiaojuan Chen, Yuanyuan Ren, Wei Wei, Jingliao Zhang, and Lixian Chang
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medicine.medical_specialty ,Pediatrics ,Candidate gene ,biology ,business.industry ,Anemia ,Spontaneous remission ,Hematology ,medicine.disease ,IDH2 ,Gastroenterology ,Leukemia ,Oncology ,Internal medicine ,Pediatrics, Perinatology and Child Health ,Cohort ,medicine ,biology.protein ,business ,Myelofibrosis ,Calreticulin - Abstract
Background Primary myelofibrosis (PMF) is quite rare in children. Mutations of JAK2V617F or MPLW515K/L were absent in pediatric patients with PMF according to previous studies. Recently, mutations in calreticulin (CALR) were described in adult patients with JAK2/MPL-unmutated PMF. Our study aimed to analyze the clinical and genetic features of Chinese pediatric patients with PMF. Procedures We retrospectively investigated 14 pediatric patients diagnosed as PMF according to WHO 2008 criteria. Direct sequencing was performed for the existence of genetic alterations in JAK2, MPL, TET2, CBL, ASXL1, IDH1, IDH2, SRSF2, EZH2, DNMT3A and CALR. Results In our cohort, all patients had anemia, three patients (21%) had splenomegaly, six patients (43%) had micromegakaryocytes at time of diagnosis. No patient had spontaneous remission and six patients (43%) transformed to acute myelocytic leukemia. In nine patients with evaluable cytogenetic information, three subjects (33%) had abnormal karyotypes. The median survival from time of diagnosis was 28 months. Seven patients (50%) had type 2 mutations of CALR. No patient had mutations in the other candidate genes. There was no statistical differences in age, gender, hemoglobin, WBC, neutrophil and platelet counts, percentage of circulating blast, overall survival and leukemia transformation between patients with and without CALR mutation. Conclusion Our study documented that Chinese pediatric patients with PMF in our cohort had its own clinical characteristics and poor outcome. CALR mutations were detected in 50% of our pediatric patients with PMF. Based on our study, CALR mutations screening could be used as molecular marker for diagnosis of pediatric patients with PMF. Pediatr Blood Cancer 2014;61:2256–2262. © 2014 Wiley Periodicals, Inc.
- Published
- 2014
40. [Copy number variations in pediatric ETV6/RUNX1 positive acute lymphoblastic leukemia]
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Yao, Zou, Li, Zhang, Xiaoming, Liu, Ye, Guo, Wenyu, Yang, Jiayuan, Zhang, Fang, Liu, Tianfeng, Liu, Shuchun, Wang, Xiaojuan, Chen, Min, Ruan, Benquan, Qi, Lixian, Chang, Yumei, Chen, and Xiaofan, Zhu
- Subjects
Repressor Proteins ,Survival Rate ,Adolescent ,DNA Copy Number Variations ,Proto-Oncogene Proteins c-ets ,Core Binding Factor Alpha 2 Subunit ,Humans ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Child ,Prognosis ,Multiplex Polymerase Chain Reaction ,Disease-Free Survival - Abstract
To evaluate the copy number variations (CNVs) in pediatric ETV6/RUNX1 gene positive acute lymphoblastic leukemia(ALL) and its correlation with clinical features and prognosis.Totally 141 children (14 years of age) with newly diagnosed ETV6/RUNX1 positive ALL in Institute of Hematology and Blood Diseases Hospital, were included from January 2006 to November 2012. The CNVs were analyzed by multiplex ligation-dependent probe amplification (MLPA). The survival rate between the patients with CNVs were explored. Overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier method and compared with the log-rank test.Among the 141 cases, 55.3% (n=78) were boys and 44.7% (n=63) were girls and the median age was 4 (1-13) years. The estimated 5-year DFS rate for the patients was (84±4)%. The estimated 5-year OS rate for the patients was (85±4)%. Ninety-five patients were tested MLPA. CNVs were detected in 73 cases (76.8%). CNVs of genes EBF1(15.8%), CDKN2A/2B(18.9%), PAX5(21.1%), ETV6(54.8%), BTG1(10.5%) were detected in more than 10% of the patients. Among the 95 patients, EBF1 deletions were found in 9 patients and EBF1 amplifications were found in 6 patients; 5-year recurrence-free survival (RFS) was statistically significant among 3 groups (χ(2)=9.809, P=0.007) . PAX5 deletions were found in 13 patients and PAX5 amplifications were found in 7 patients; the difference in 5-year RFS was statistically significant between 3 groups(χ(2)=7.622, P=0.022). ETV6 deletions were found in 39 patients and ETV6 amplifications were found in 13 patients; the difference in 5-year RFS was statistically significant among the 3 groups (χ(2)=11.045, P=0.004).The CNVs had prognostic relevance in ETV6/RUNX1 positive ALL.
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- 2016
41. Clinical features, mutations and treatment of 104 patients of Diamond-Blackfan anemia in China: a single-center retrospective study
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Weiping Yuan, Xiaojuan Chen, Ye Guo, Ran-Ran Zhang, Yingchi Zhang, Lixian Chang, Yang Wan, Xiaofan Zhu, Min Ruan, Jingliao Zhang, Yumei Chen, Wenbin An, Shuai Zhu, Yao Zou, and Wenyu Yang
- Subjects
0301 basic medicine ,Male ,Ribosomal Proteins ,medicine.medical_specialty ,China ,Blood transfusion ,Anemia ,medicine.medical_treatment ,Single Center ,03 medical and health sciences ,0302 clinical medicine ,Prednisone ,Internal medicine ,Medicine ,Humans ,Blood Transfusion ,Diamond–Blackfan anemia ,Age of Onset ,Anemia, Diamond-Blackfan ,Retrospective Studies ,Hematology ,business.industry ,Retrospective cohort study ,medicine.disease ,Surgery ,030104 developmental biology ,Treatment Outcome ,030220 oncology & carcinogenesis ,Mutation ,Drug Therapy, Combination ,Female ,Age of onset ,business ,medicine.drug - Abstract
Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by a paucity of erythroid progenitors. We summarized the clinical and genetic features of 104 DBA patients in a single-center retrospective study in China. Data of DBA patients who received consultations at our center from 2003 to 2015 were analyzed retrospectively. Genes encoding 10 ribosomal proteins (RPs) and GATA1 were sequenced for mutation detection. Our cohort was composed of 65 males and 39 females. Congenital malformations were observed in 19 patients. Mutations of the RP genes were detected in 58.3 % patients. Twenty different mutations were first reported. Thirty-four patients received prednisone combined with CsA therapy, and improvement was observed in 20 cases. During follow-up for a median 39 months, 33.7 % of the patients achieved remission, 41.3 % of the patients were persistently transfusion independent, 21.7 % of the patients were transfusion dependent, and three patients died. The patient group with detected mutations had a younger age of disease onset, a higher malformation rate, and tended to have a lower remission rate and a higher transfusion-dependence rate. Prednisone in combination with cyclosporine A can be a second-line choice for DBA patients. Differences were detected between DBA patients with and without detectable mutations in the genes studied.
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- 2016
42. [Significance of ikaros family zinc finger 1 deletion in pediatric B-acute lymphoblastic leukemia without reproducible cytogenetic abnormalities]
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Xiaoming, Liu, Li, Zhang, Yao, Zou, Lixian, Chang, Wei, Wei, Min, Ruan, Yumei, Chen, Wenyu, Yang, Xiaojuan, Chen, Ye, Guo, Shuchun, Wang, Tianfeng, Liu, Jiayuan, Zhang, Fang, Liu, Benquan, Qi, Wenbin, An, and Xiaofan, Zhu
- Subjects
Chromosome Aberrations ,Ikaros Transcription Factor ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,Humans ,Zinc Fingers ,Exons ,Child ,Prognosis ,Multiplex Polymerase Chain Reaction ,Disease-Free Survival ,Gene Deletion - Abstract
To identify ikaros family zinc finger1 (IKZF1) deletion in patients with pediatric B cells-acute lymphoblastic leukemia (B-ALL) without reproducible chromosomal abnomalities and further investigate its value in this part of patients' pathogenesis and prognosis.The study was approved by the institutional review board of the authors' hospital and informed consent was obtained from the patients and/or their legal guardians. Data of 96 children with B-ALL patients without reproducible cytogenetic abnormalities whose bone marrows specimens were enough for DNA extraction for the detection were retrospectively selected. All the patients were diagnosed and systematically treated according to CCLG-ALL2008 in our hospital from April 2008 to April 2013. The 96 patients were divided into two groups according to the result of IKZF1's detection by multiplex ligation-dependent probe amplification (MLPA): The cases that with any of eight exons of IKZF1 deleted were entered into"Group with IKZF1 deletion"otherwise entered"Group without IKZF1 deletion". Disease free survival (DFS), event-free survival (EFS) and overall survival (OS) were compared between the two groups.Nineteen out of 96 B-ALL patients without reproducible cytogenetic abnormalities had IKZF1 deletion (20%). Three of 19 patients with IKZF1 deletions of the whole gene; ten of 19 patients with IKZF1 deletions of exon 1; 4 of 19 patients with IKZF1 deletions of exons 4-7; one of 19 patients with IKZF1 deletions of exons 2-7 and one of 19 patients with IKZF1 deletions of exons 1-6. Whose white blood cell (WBC) ≥ 50 × 10(9)/L inIKZF1 diletion group was more than whthout IKZF1 deletion group(42% vs. 13%, P=0.004). Patients with IKZF1 deletions had a lower 3-year DFS (0.67 ± 0.13 vs. 0.93 ± 0.04, P=0.001); EFS (0.67 ± 0.13 vs. 0.90 ± 0.04, P = 0.012) and OS(0.79 ± 0.09 vs. 0.96 ± 0.02, P=0.010) compared to those without IKZF1 deletions. Excluding the influence of sex, age, WBC count at diagnosis, cerebrospinal fluid state and prednisone response IKZF1 deletion still affected the patients' DFS, EFS and OS ( P0.05 for all comparisons).Some of pediatric B-cell precursor ALL without reproducible cytogenetic abnormalities had been detected to have IKZF1 deletion; IKZF1 deletion is an independent poor prognostic factor in these patients.
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- 2016
43. UV Nonlinear Optical Crystal Ba2[B6O9(OH)4] Featuring Unique Chiral Layers with a New B18O42 Circle Based on BO3 and BO4 Units
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Shilie Pan, Jianyang Hu, Lixian Chang, Hongwei Yu, and Li Wang
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Inorganic Chemistry ,Crystallography ,Chemistry ,Physical and Theoretical Chemistry ,Nonlinear optical crystal ,Hydrothermal circulation - Abstract
A new noncentrosymmetric polyborate, Ba(2)[B(6)O(9)(OH)(4)], has been synthesized under a hydrothermal condition. The polyborate contains chiral layers constructed by two kinds of helical chains and also form new B(18)O(42) circles based on B(3)O(8) units [(3: Δ+2T)]. One kind of Ba atom locates in the cavity surrounded by the B(11)O(11) ring within the anion layer, and the other kind of Ba atom inserts between two adjacent layers. UV-vis diffuse reflectance spectroscopy demonstrates that the compound has a cutoff edge below 190 nm and has a large second-harmonic generation (SHG) effect, which is approximately 3 times that of KH(2)PO(4) (KDP) and is type-I phase matchable.
- Published
- 2012
44. Systematic investigation on morphologies, forming mechanism, photocatalytic and photoluminescent properties of ZnO nanostructures constructed in ionic liquids
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Li Wang, Lixian Chang, Bin Zhao, Zhongyong Yuan, Gaosong Shao, and Wenjun Zheng
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Zinc oxide -- Structure ,Zinc oxide -- Chemical properties ,Zinc oxide -- Optical properties ,Chemical synthesis -- Analysis ,Photoluminescence -- Analysis ,Ionic solutions -- Optical properties ,Chemistry - Abstract
A series of shape-controllable ZnO nanostructures are synthesized in ionic liquids by a simpler, only one-step, low-temperature route and characterized by surface area measurement and photoluminescence. The relationship between the structure of ionic liquids and the morphology of ZnO nanostructures is examined for the first time.
- Published
- 2008
45. Fabrication and Properties of Eight Novel Lanthanide−Organic Frameworks Based on 4-Hydroxypyran-2,6-dicarboxylate and 4-Hydroxypyridine-2,6-dicarboxylate
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Ya Zuo, Ming Fang, Zhi Chen, Bin Zhao, Xuhui Liu, and Lixian Chang
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Lanthanide ,Lanthanide contraction ,Inorganic chemistry ,chemistry.chemical_element ,General Chemistry ,Condensed Matter Physics ,Magnetic susceptibility ,Oxalate ,Crystallography ,chemistry.chemical_compound ,chemistry ,Dysprosium ,General Materials Science ,Lamellar structure ,Isostructural ,Luminescence - Abstract
Eight novel lanthanide−organic frameworks, [Ln(CDA)] (Ln = Pr (1), Nd (2), Sm (3), CDA = 4-hydroxypyran-2,6-dicarboxylate), [Ho(CDA)(H2O)] (4), [Pr(HCDA)(C2O4)0.5(H2O)2] (5), [Lu(CDA)Ba2(C2O4)2(H2O)2]·0.25CH3OH (6), [Dy(HCAM)2(CAM)Ba2(H2O)9.75]·7.625H2O ((7), CAM = 4-hydroxypyridine-2,6-dicarboxylate), [Sm2(CAM)4Ba3(H2O)2] (8), have been synthesized under hydrothermal conditions. They were structurally characterized by single-crystal X-ray diffraction. Compounds 1−3 are isostructural and display novel three-dimensional (3D) architectures, and compound 4 features a two-dimensional (2D) double-layer structure. The structural divergence between 1−3 and 4 may originate from a lanthanide contraction effect. By increasing the temperature during the synthesis of 1, CDA was partly decomposed into oxalate ions, and as a result, compound 5 with a 3D framework different from that of 1 was obtained. The Lu-based compound isostructural to 4 has not been obtained so far under synthetic conditions similar to that of 1−4...
- Published
- 2009
46. Analysis of long-term follow-up and examination of pathological liver tissue in chronic hepatitis E
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Weikun Li, Huimin Li, Lixian Chang, Yingrong Du, Li Liu, Yunhua Liu, Chunyun Liu, and Ting Jia
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Adult ,Male ,medicine.medical_specialty ,Cirrhosis ,medicine.disease_cause ,Gastroenterology ,Organ transplantation ,03 medical and health sciences ,0302 clinical medicine ,Hepatitis E virus ,Liver Function Tests ,Fibrosis ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Aged ,Hepatitis, Chronic ,Hepatology ,medicine.diagnostic_test ,business.industry ,Hepatitis B ,Middle Aged ,medicine.disease ,Hepatitis E ,Liver ,030211 gastroenterology & hepatology ,Female ,business ,Liver cancer ,Liver function tests ,Follow-Up Studies - Abstract
Hepatitis E is chronic in immunocompromised patients with HIV infection, organ transplant, or radiation and chemotherapy. General cases are not chronic. Fifty-five cases were collected and followed up for 4-14 years. It was found that chronic hepatitis E is more common in males, but a high degree of inflammatory activity and fibrosis was not evident. After 4-14 years of follow-up observation, cirrhosis or liver cancer did not appear. This is significantly different from the hepatitis B and C viruses. We speculated that the chronic mechanism in the general patients with hepatitis E might be different from that of immunocompromised cases.
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- 2015
47. Prediction of outcomes by early treatment responses in childhood T-cell acute lymphoblastic leukemia: a retrospective study in China
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Lixian Chang, Yang Wan, Tianfeng Liu, Xiaojuan Chen, Wenyu Yang, Xiaofan Zhu, Wei Wei, Wenbin An, Ye Guo, Yumei Chen, and Yao Zou
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Male ,China ,medicine.medical_specialty ,Neoplasm, Residual ,Adolescent ,Antineoplastic Agents, Hormonal ,Disease ,Disease-Free Survival ,Bone Marrow ,Prednisone ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Pediatrics, Perinatology, and Child Health ,Child ,Survival rate ,Retrospective Studies ,Hematology ,business.industry ,Minimal residual disease ,Infant ,Induction chemotherapy ,Retrospective cohort study ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Prognosis ,Childhood ,Tumor Burden ,Prednisone response ,Survival Rate ,body regions ,Treatment Outcome ,medicine.anatomical_structure ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Immunology ,Female ,Bone marrow ,business ,T-cell acute lymphoblastic leukemia ,Research Article ,medicine.drug - Abstract
Background Early treatment responses are important prognostic factors in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. The predictive values of early treatment responses in Chinese childhood T-ALL patients were still unknown. Methods From January 2003 to December 2012, 74 consecutive patients aged ≤15 years with newly diagnosed T-ALL were treated with BCH-2003 protocol or CCLG-2008 protocol in the Department of Pediatric, Institute of Hematology and Blood Diseases Hospital in China. Predictive values of early treatment responses, including prednisone response, bone marrow morphology at day 15 and day 33 during induction chemotherapy, and minimal residual disease (MRD) monitored by flow cytometry after induction therapy (time point 1, TP1) and before consolidation therapy (time point 2, TP2), were analyzed. Results The 5-year event free survival (EFS) and overall survival (OS) rates for these patients were 62.5 % (SE, 6.4) and 62.7 % (SE, 6.6), respectively. Prednisone poor responder was strongly associated with increased chance of induction failure (14.8 %) and decreased survival rate (5 year EFS rate, 51.1 % (SE, 10.5)). Patients with ≥25 % blast cells in bone marrow at day 15 were more likely to have an inferior outcome. 93.2 % of the T-ALL patients achieved complete remission at day 33 while patients with resistant disease all died of disease progression. MRD ≥10−2 at TP1 or MRD ≥10−3 at TP2 was significantly related to dismal prognosis. Risk groups classified by MRD at two time points could stratify patients into different groups: 29.0 % of the patients were MRD standard risk (MRD
- Published
- 2015
48. [Diagnosis and treatment of Fanconi anemia]
- Author
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Lixian, Chang and Xiaofan, Zhu
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Fanconi Anemia ,Humans - Published
- 2015
49. [Treatment outcome of childhood standard-risk and median-risk acute lymphoblastic leukemia with CCLG-2008 protocol]
- Author
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Xiaoming, Liu, Yao, Zou, Huijun, Wang, Xiaojuan, Chen, Min, Ruan, Yumei, Chen, Wenyu, Yang, Ye, Guo, Tianfeng, Liu, Li, Zhang, Shuchun, Wang, Jiayuan, Zhang, Fang, Liu, Xiaojin, Cai, Benquan, Qi, Lixian, Chang, and Xiaofan, Zhu
- Subjects
Male ,Neoplasm, Residual ,Adolescent ,Remission Induction ,Infant ,Antineoplastic Agents ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Flow Cytometry ,Prognosis ,Disease-Free Survival ,Survival Rate ,Treatment Outcome ,Bone Marrow ,Recurrence ,Child, Preschool ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Female ,Prospective Studies ,Child - Abstract
To estimate the significance of the adjustment of acute lymphoblastic leukemia (ALL) risk group by monitoring minimal residual disease(MRD).Totally 285 children ALL patients who were diagnosed and systematically treated according to CCLG-2008 in Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC, from April 2008 to August 2011 were prospectively selected. Among these cases, 62.8% (n = 179) were boys and 37.2% (n = 106) were girls and the median age was 5.3(0.5-14.0). The patients who were at high-risk group initially were excluded. The grouping of cases: the patients were divided into two groups according to the dates of initial diagnosis. Group I had 126 patients who were initially diagnosed between April 2008 and December 2009 in whom therapeutic regimen was not adjusted by reassignment of risk group by MRD. Group II had 159 patients who were initially diagnosed between January 2010 and August 2011 whose therapeutic regimen was adjusted by reassignment of risk group by MRD at specific time (33rd day of induction chemotherapy and 12 weeks after the beginning of chemotherapy). MP-FCM Coulter FC-500 was used in the detection of MRD.Among these 285 patients, 94.0% (n = 268) were diagnosed as B-lineage acute lymphoblastic leukemia and 6.0% (n = 17) were T-lineage acute lymphoblastic leukemia. In group I, 61.9% (n = 78) patients belonged to low-risk group, 38.1% (n = 48) median-risk; in group II, before the adjustment, the rates of the low-risk group and median-risk group were 68.6% (n = 109) and 31.4% (n = 50) , respectively, while after the adjustment they were altered to 53.5% (n = 85) and 39.6% (n = 63) , furthermore 6.9% (n = 11) patients went into the high-risk group. Both groups were followed up for 2.5 years after their diagnoses, the disease of 7.4% (n = 21) patients relapsed, and the rates of two groups were 12.7% (n = 16) and 3.1% (n = 5) respectively, P = 0.009. The rate of serious infection (such as sepsis, pulmonary infection) of all these patients was 32.3% (92/285) , there was no significant difference between the two groups [28.6% (36/126) vs.35.2% (56/159) , P = 0.392]. The mortality of all these patients was 6.7% (19/285) , and that of group I was higher than that of group II [10.3% (13/126) vs. 3.8% (6/159) , P = 0.044]. The 2.5 years overall survival (OS), event-free survival (EFS) and disease-free survival (DFS) of group I were all lower than those of group II in Kaplan-Meier survivorship analysis (all P0.05). The two groups were followed up for 2.5 years after their diagnoses, after elimination of the confounding influence of sex, age, FAB subtype, WBC count, ratio of blast cells in bone marrow at diagnosed, chromosome karyotype and fusion gene, reassignment of risk group by MRD was used to calculate the OS, EFS and DFS of ALL patients (all P0.05). After the adjustment the risk group was more significant in the assessment of prognosis.The reassignment of risk group in low and median risk groups children with acute lymphoblastic leukemia by MRD did not increase the rate of serious infection but could reduce the relapse rate and mortality, and was beneficial to increase the patients' OS, EFS and DFS.
- Published
- 2014
50. ChemInform Abstract: A Nitrate Nonlinear Optical Crystal Pb16(OH)16(NO3)16with a Large Second-Harmonic Generation Response
- Author
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Xin Su, Reshalaiti Hailili, Hongwei Yu, Lixian Chang, Zhihua Yang, Shilie Pan, and Li Wang
- Subjects
chemistry.chemical_compound ,Aqueous solution ,Nitrate ,Chemistry ,Yield (chemistry) ,Analytical chemistry ,Second-harmonic generation ,General Medicine ,Nonlinear optical crystal ,Block (periodic table) ,Autoclave - Abstract
Colorless block crystals of the title compound are hydrothermally prepared from aqueous mixtures of Pb(NO3)2 and LiOOH (autoclave, 200 °C, 72 h, 92% yield).
- Published
- 2014
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