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Outcomes of haploidentical bone marrow transplantation in patients with severe aplastic anemia-II that

《医学前沿（英文）》 2021年 第15卷 第5期   页码 718-727 doi: 10.1007/s11684-020-0807-4

摘要： Severe aplastic anemia II (SAA-II) progresses from non-severe aplastic anemia (NSAA). The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation (haplo-BMT) in patients lacking a human leukocyte antigen (HLA)-matched donor. This study aimed to investigate the efficacy of haplo-BMT for patients with SAA-II. Twenty-two patients were included and followed up, and FLU/BU/CY/ATG was used as conditioning regimen. Among these patients, 21 were successfully engrafted, 19 of whom survived after haplo-BMT. Four patients experienced grade II–IV aGvHD, including two with grade III–IV aGvHD. Six patients experienced chronic GvHD, among whom four were mild and two were moderate. Twelve patients experienced infections during BMT. One was diagnosed with post-transplant lymphoproliferative disorder and one with probable EBV disease, and both recovered after rituximab infusion. Haplo-BMT achieved 3-year overall survival and disease-free survival rate of 86.4%±0.73% after a median follow-up of 42 months, indicating its effectiveness as a salvage therapy. These promising outcomes may support haplo-BMT as an alternative treatment strategy for patients with SAA-II lacking HLA-matched donors.

关键词： severe aplastic anemia     non-severe acquired aplastic anemia     haploidentical bone marrow transplantation     outcomes    

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Autologous bone marrow stem cell transplantation for the treatment of ulcerative colitis complicated

null

《医学前沿（英文）》 2016年 第10卷 第4期   页码 522-526 doi: 10.1007/s11684-016-0485-4

摘要：

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with continuous or recurrent symptoms. A 42-year-old male patient with intermittent diarrhea accompanied by bloody mucopurulent stools was admitted to our hospital. The diagnosis of UC was confirmed by a combination of laboratory examination, colonoscopy, and histological assay. The patient developed herpes zoster in the hospital, which challenged traditional treatments. Therefore, we performed an autologous bone marrow cells to modulate the immune system with his permission. Autologous bone marrow mononuclear cells were collected and injected locally into the bowel mucosa, and subsequently injected systemically through a peripheral vein. After the patient underwent auto bone marrow mononuclear cells transplantations twice, the patient’s symptoms were alleviated. Furthermore, he recovered from hematochezia, and his hypersensitive C reactive protein decreased. Colonoscopy results showed reduced lesions and decreased areas with bleeding and edema in the sigmoid colon and rectum. No recurrence occurred in the subsequent two years, but long-time monitoring is still necessary for the prophylaxis of colorectal cancer.

关键词： autograft     bone marrow stem cells     ulcerative colitis     cell therapy    

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自体骨髓干细胞移植研究进展

李连达,吴理茂,刘红,宁可永,李贻奎

《中国工程科学》 2004年 第6卷 第8期   页码 1-4

摘要：

细胞移植作为一种新的治疗方法备受医学界关注，但细胞供应短缺和免疫排斥是阻碍这一疗法临床推广的主要难题。自体骨髓干细胞移植在一定程度上可缓解此矛盾。文章综述了自体骨髓干细胞移植治疗脑、肝、心等重要器官疾病的基础和临床研究现状，以及骨髓动员剂在骨髓干细胞移植中的作用。

关键词： 骨髓干细胞     自体移植     骨髓动员剂    

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FGF13 suppresses acute myeloid leukemia by regulating bone marrow niches

《医学前沿（英文）》 2022年 第16卷 第6期   页码 896-908 doi: 10.1007/s11684-022-0944-z

摘要： Fibroblast growth factor 13 (FGF13) is aberrantly expressed in multiple cancer types, suggesting its essential role in tumorigenesis. Hence, we aimed to explore its definite role in the development of acute myeloid leukemia (AML) and emphasize its associations with bone marrow niches. Results showed that FGF13 was lowly expressed in patients with AML and that its elevated expression was related to prolonged overall survival (OS). Univariate and multivariate Cox regression analyses identified FGF13 as an independent prognostic factor. A prognostic nomogram integrating FGF13 and clinicopathologic variables was constructed to predict 1-, 3-, and 5-year OS. Gene mutation and functional analyses indicated that FGF13 was not associated with AML driver mutations but was related to bone marrow niches. As for immunity, FGF13 was remarkably associated with T cell count, immune checkpoint genes, and cytokines. In addition, FGF13 overexpression substantially inhibited the growth and significantly induced the early apoptosis of AML cells. The xenograft study indicated that FGF13 overexpression prolonged the survival of recipient mice. Overall, FGF13 could serve as an independent prognostic factor for AML, and it was closely related to the bone marrow microenvironment.

关键词： acute myeloid leukemia     FGF13     prognosis     immune-related genes     bone marrow niches    

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自体骨髓干细胞移植与归元方联用治疗急慢性肝损伤实验研究

吴理茂,李连达,刘红,宁可永,李贻奎

《中国工程科学》 2004年 第6卷 第7期   页码 34-42

摘要：

研究中药归元方与自体骨髓干细胞移植对急慢性肝损伤的治疗作用。研究方法：用肝脏局部注射乙醇的方法复制急性局限性肝损伤模型，复合因素（CCl4、乙醇、高脂、低蛋白）刺激复制大鼠肝纤维化模型，通过定量组织学、肝功能检查、免疫组化、肝组织羟脯氨酸含量、损伤或纤维区骨髓干细胞观察等综合评价中药、自体骨髓干细胞移植及两者合用的疗效。结果：归元方与自体骨髓干细胞移植可减小肝损伤区域，改善肝功能，使纤维肝组织表达μPA增强，降低血清ALT，AST，PCⅢ，HA和肝组织羟脯氨酸的含量，改善肝组织肝纤维化评分，骨髓干细胞能在肝损伤、肝纤维化形成环境中存活、增殖，并向肝细胞分化，表达肝脏特异的角蛋白CK18。结论：归元方与自体骨髓干细胞移植对急慢性肝损伤有明确的治疗作用，两者合用可优势互补，协同增效。临床上有良好的应用前景。

关键词： 归元方     骨髓干细胞     自体移植     肝损伤     肝纤维化    

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Everyone has a donor: contribution of the Chinese experience to global practice of haploidentical hematopoieticstem cell transplantation

Meng Lv, Yingjun Chang, Xiaojun Huang

《医学前沿（英文）》 2019年 第13卷 第1期   页码 45-56 doi: 10.1007/s11684-017-0595-7

摘要： Human leukocyte antigen (HLA)-matched donors for hematopoietic stem cell transplantation (HSCT) have long been scarce in China. Haploidentical (haplo) donors are available for the vast majority of patients, but toxicity has limited this approach. Three new approaches for haplo-HSCT originated from Italy, China, and USA in 1990 and have been developed to world-renowned system up to now. The Chinese approach have been greatly improved by implementing new individualized conditioning regimens, donor selection based on non-HLA systems, risk-directed strategies for graft-versus-host disease and relapse, and infection management. Haplo-HSCT has exhibited similar efficacy to HLA-matched HSCT and has gradually become the predominant donor source and the first alternative donor choice for allo-HSCT in China. Registry-based analyses and multicenter studies adhering to international standards facilitated the transformation of the unique Chinese experience into an inspiration for the refinement of global practice. This review will focus on how the new era in which “everyone has a donor” will become a reality in China.

关键词： haploidentical hematopoietic stem cell transplantation     conditioning     graft-versus-host disease     relapse     infection     donor selection    

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Pluripotent stem cells exhibiting similar characteristics can be isolated from human fetal bone marrow

FANG Baijun, SONG Yongping, LIN Quande, ZHAO Chunhua, SHI Mingxia

《医学前沿（英文）》 2007年 第1卷 第2期   页码 185-191 doi: 10.1007/s11684-007-0035-1

摘要： Previously, we reported that a cell population derived from human fetal bone marrow (BM), termed here Flk1CD34 postembryonic pluripotent stem cells (PPSCs) that have the characteristics of mesenchymal stem cells (MSCs), could differentiate into ectodermal, endodermal and mesodermal cell types at the single cell level , and that these cells could also differentiate into the epithelium of liver, lung, gut, as well as the hematopoietic and endothelial lineages after transplantion into irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. In this study, we further isolated pluripotent stem cells from human fetal heart, liver, muscle, lung, derma, kidney, and fat and then analyzed the characteristics and function of these stem cells. It was found that the phenotype of the culture-expanded pluripotent stem cells from different fetal tissues was similar to BM-derived Flk1CD34 PPSCs, i.e. Flk1 and CD44 positive, GlyA, CD34, CD45, class I-HLA and HLA-DR negative. Morphologically, these cells were fibroblast-like and the doubling time was about 30 h. More importantly, culture-expanded pluripotent stem cells from all these fetal tissues were able to differentiate into cells with morphologic and phenotypic characteristics of adipocytes, osteocytes, neurons, glial cells and hepatocytes. These pluripotent stem cells with characteristics similar to fetal BM-derived Flk1CD34 PPSCs can be selected and cultured from tissues other than the BM. This phenomenon may help explain the stem cell plasticity found in multiple human tissues. In addition, as fetal BM-derived Flk1CD34 PPSCs, these pluripotent stem cells from different fetal tissues had the capacity for self-renewal and multi-lineage differentiation even after being expanded for more than 40 population doublings . Thus, they may be an ideal source of stem cells for treatment of inherited or degenerative diseases.

关键词： endothelial     phenomenon     ectodermal     Flk1CD34 postembryonic     irradiated non-obese    

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大鼠骨髓间质干细胞的分离纯化与鉴定

张荣利,冯　雪,张会亮,罗国安,李连达,王义明

《中国工程科学》 2007年 第9卷 第7期   页码 89-94

摘要：

采用密度梯度离心法分离骨髓间质干细胞，差速贴壁法进行纯化，应用流式细胞仪、激光共聚焦显微镜等对纯化细胞进行鉴定，结果细胞表面抗原CD29，CD44，CD105，CD166表达呈阳性，而CD14，CD34，CD45表达呈阴性。采用RT唱PCR鉴定了三个基因：nestin，NST，Oct-４，前两者呈阳性表达，后者弱阳性表达。这些细胞特异抗原与基因表达综合起来，表明得到的细胞具备骨髓间质干细胞的特性。密度梯度分离与差速贴壁相结合，可获得较好均一性的骨髓间质干细胞，是一种简单可靠、易于推广的骨髓干细胞获取方法，可为细胞与组织工程研究提供种子细胞。

关键词： 大鼠     骨髓间质干细胞     流式细胞分析    

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the intensity and loading time of direct current electric field on the directional migration of rat bonemarrow mesenchymal stem cells

null

《医学前沿（英文）》 2016年 第10卷 第3期   页码 286-296 doi: 10.1007/s11684-016-0456-9

摘要：

Exogenic electric fields can effectively accelerate bone healing and remodeling through the enhanced migration of bone marrow mesenchymal stem cells (BMSCs) toward the injured area. This study aimed to determine the following: (1) the direction of rat BMSC (rBMSC) migration upon exposure to a direct current electric field (DCEF), (2) the optimal DCEF intensity and duration, and (3) the possible regulatory role of SDF-1/CXCR4 axis in rBMSC migration as induced by DCEF. Results showed that rBMSCs migrated to the positive electrode of the DCEF, and that the DCEF of 200 mV/mm for 4 h was found to be optimal in enhancing rBMSC migration. This DCEF strength and duration also upregulated the expression of osteoblastic genes, including ALP and OCN, and upregulated the expression of ALP and Runx2 proteins. Moreover, when CXCR4 was inhibited, rBMSC migration due to DCEF was partially blocked. These findings indicated that DCEF can effectively induce rBMSC migration. A DCEF of 200 mV/mm for 4 h was recommended because of its ability to promote rBMSC migration, proliferation, and osteogenic differentiation. The SDF-1/CXCR4 signaling pathway may play an important role in regulating the DCEF-induced migration of rBMSCs.

关键词： DCEF     migration     osteogenesis differentiation     rBMSCs     SDF-1/CXCR-4    

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Positive stool culture could predict the clinical outcomes of haploidentical hematopoietic stem celltransplantation

Lijuan Hu, Qi Wang, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Kaiyan Liu, Hui Wang, Xiaojun Huang, Xiaodong Mo

《医学前沿（英文）》 2019年 第13卷 第4期   页码 492-503 doi: 10.1007/s11684-019-0681-0

摘要： We aimed to identify the effect of positive stool cultures (PSCs) on the clinical outcomes of patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT) ( = 332). PSCs were observed in 61 patients (PSC group, 18.4%). Enterobacteriaceae in stool specimens was associated with a higher risk of bloodstream infection, and in stool specimens was related to a higher risk of platelet engraftment failure. The cumulative incidence of infection-related mortality 1 year after haplo-HSCT in the PSC group was higher than that of the patients who showed persistently negative stool cultures (NSC group; 19.2% vs. 8.9%, = 0.017). The probabilities of overall survival (71.4% vs. 83.8%, = 0.031) and disease-free survival (69.6% vs. 81.0%, = 0.048) 1 year after haplo-HSCT for the PSC group were significantly lower than those for the NSC group, particularly for patients who had in their stool specimens. In multivariate analysis, in stool specimens significantly increased the risk of mortality and was associated with poorer survival. Our results showed that PSC influenced the clinical outcomes after haplo-HSCT, particularly those who had in their stool specimens.

关键词： haploidentical     hematopoietic stem cell transplantation     stool culture     Candida    

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Comparison of reference values for immune recovery between event-free patients receiving haploidentical

null

《医学前沿（英文）》 2018年 第12卷 第2期   页码 153-163 doi: 10.1007/s11684-017-0548-1

摘要：

To establish optimal reference values for recovered immune cell subsets, we prospectively investigated post-transplant immune reconstitution (IR) in 144 patients who received allogeneic stem cell transplantation (allo-SCT) and without showing any of the following events: poor graft function, grades II?IV acute graft-versus-host disease (GVHD), serious chronic GVHD, serious bacterial infection, invasive fungal infection, or relapse or death in the first year after transplantation. IR was rapid in monocytes, intermediate in lymphocytes, CD3+ T cells, CD8+ T cells, and CD19+ B cells, and very slow in CD4+ T cells in the entire patient cohort. Immune recovery was generally faster under HLA-matched sibling donor transplantation than under haploidentical transplantation. Results suggest that patients with an IR comparable to the reference values display superior survival, and the levels of recovery in immune cells need not reach those in healthy donor in the first year after transplantation. We suggest that data from this recipient cohort should be used as reference values for post-transplant immune cell counts in patients receiving HSCT.

关键词： immune reconstitution     hematopoietic stem cell transplantation     event-free patients     reference range    

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Toll-like receptor signaling in hematopoietic homeostasis and the pathogenesis of hematologic diseases

null

《医学前沿（英文）》 2015年 第9卷 第3期   页码 288-303 doi: 10.1007/s11684-015-0412-0

摘要：

Toll-like receptors (TLRs), which are found in innate immune cells, are essential mediators of rapid inflammatory responses and appropriate T-cell activation in response to infection and tissue damage. Accumulating evidence suggests that TLR signaling is involved in normal hematopoiesis and specific hematologic pathologies. Particular TLRs and their downstream signaling mediators are expressed not only in terminally differentiated innate immune cells but also in early hematopoietic progenitors. Sterile activation of TLR signaling is required to generate early embryonic hematopoietic progenitor cells. In adult animals, TLR signaling directly or indirectly promotes differentiation of myeloid cells at the expense of that of lymphoid cells and the self-renewal of hematopoietic stem cells during infection and tissue damage. Activating mutations of the MyD88 gene, which codes for a key adaptor involved in TLR signaling, are commonly detected in B-cell lymphomas and other B-cell hematopathologies. Dysregulated TLR signaling contributes to the pathogenesis of many hematopoietic disorders, including bone marrow failure, myelodysplastic syndrome, and acute myeloid leukemia. Complete elucidation of the molecular mechanisms by which TLR signaling mediates the regulation of both normal and pathogenic hematopoiesis will prove valuable to the development of targeted therapies and strategies for improved treatment of hematopoietic disorders.

关键词： TLR     MyD88     hematopoiesis     bone marrow failure     leukemia     myelodysplastic syndrome    

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疾病危险度-共患病指数在单倍型造血干细胞移植中的应用 Article

莫晓冬, 张晓辉, 许兰平, 王昱, 闫晨华, 陈欢, 陈育红, 韩伟, 王峰蓉, 王景枝, 刘开彦, 黄晓军

《工程（英文）》 2021年 第7卷 第2期   页码 162-169 doi: 10.1016/j.eng.2020.12.005

摘要：

本文的研究目的是基于疾病危险度指数（disease risk index, DRI）和造血干细胞移植共患病指数（hematopoietic cell transplantation-specificcomorbidity index, HCT-CI），提出适合单倍型造血干细胞移植（haploidentical hematopoietic stem cell transplantation, haplo-HSCT

关键词： 疾病风险指数     疾病风险共病指数     造血细胞移植     共病指数     造血干细胞移植     单倍体    

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Risk factors for chronic graft-versus-host disease after anti-thymocyte globulin-based haploidenticalhematopoietic stem cell transplantation in acute myeloid leukemia

Meng Lv, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Wei Han, Fengrong Wang, Jingzhi Wang, Kaiyan Liu, Xiaojun Huang, Xiaodong Mo

《医学前沿（英文）》 2019年 第13卷 第6期   页码 667-679 doi: 10.1007/s11684-019-0702-z

摘要： Chronic graft-versus-host disease (cGVHD) is a major complication following unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT). We aimed to identify the risk factors for cGVHD in patients who underwent anti-thymocyte globulin-based haplo-HSCT for acute myeloid leukemia ( =280). The diagnosis of cGVHD was in accordance with the National Institutes of Health consensus criteria. A total of 169 patients suffered from cGVHD. The patients who had 3 loci mismatched had a higher 8-year incidence of cGVHD (total, 66.0% vs. 53.7%, =0.031; moderate to severe, 42.4% vs. 30.1%, =0.036) than the patients who had 1 to 2 loci mismatched. The patients who had maternal donors had a higher 8-year incidence of moderate to severe cGVHD (49.2% vs. 32.9%, =0.024) compared with the patients who had other donors. The patients who had grades III to IV acute GVHD (aGVHD) had higher 8-year incidence of cGVHD (total, 88.0% vs. 50.4%, <0.001; moderate to severe, 68.0% vs. 27.0%, <0.001) compared with the patients without aGVHD. In multivariate analysis, grades III to IV aGVHD was the only independent risk factor for cGVHD. Thus, further interventions should be considered in patients with severe aGVHD to prevent cGVHD.

关键词： acute graft-versus-host disease     chronic graft-versus-host disease     National Institutes of Health consensus criteria     acute myeloid leukemia     anti-thymocyte globulin    

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Hemophagocytic lymphohistiocytosis: critical reappraisal of a potentially under-recognized condition

null

《医学前沿（英文）》 2013年 第7卷 第4期   页码 492-498 doi: 10.1007/s11684-013-0292-0

摘要：

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially life threatening, hyper inflammatory syndrome of diverse etiologies. Cardinal signs include prolonged fever, organomegaly, and persistent unexplained cytopenias. In spite of the well known diagnostic criteria put forth by HLH society, this continues to pose great diagnostic challenge in both pediatric and adult intensive care settings. We describe 4 adult (2 males, 2 females, aged 19, 29, 40, and 17 years) and 3 pediatric (2 males, 1female, aged 1 month, 6 months, and 12 years) patients with secondary HLH who satisfied the HLH-2004 diagnostic criteria. Definite evidence of hemophagocytosis was noted in 4 patients on initial bone marrow examination. The underlying etiologies were as follows: Rickettsia tsutsugamushi (case 1), autoimmune disorder (case 2), systemic onset juvenile idiopathic arthritis (sJIA) (case 3), unknown bite (possibly a venomous snake) (case 4), Plasmodium vivax (case 5), Cytomegalo virus (case 6), and Mycobacterium tuberculosis (case 7). In one patient, hemophagocytosis was presumed to have been exacerbated by administration of granulocyte monocyte colony stimulating factor (GM-CSF) for severe neutropenia. Two patients died with disseminated intravascular coagulation (DIC) and multi organ failure within few days of HLH diagnosis. Immunosuppressive therapy was started in 3 patients, and etoposide was started in one patient only. Due to lack of specificity of diagnostic criteria, diagnosing and differentiating HLH from its closest mimickers like sepsis/septic shock may be quite challenging in critically ill patients. Therefore, increasing awareness among physicians is essential for early diagnosis and effective therapy to reduce the mortality.

关键词： hemophagocytic lymphohistiocytosis     diagnosis     therapy     GM-CSF     bone marrow    

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标题 作者 时间 类型 操作

Outcomes of haploidentical bone marrow transplantation in patients with severe aplastic anemia-II that

期刊论文

Autologous bone marrow stem cell transplantation for the treatment of ulcerative colitis complicated

null

期刊论文

自体骨髓干细胞移植研究进展

李连达,吴理茂,刘红,宁可永,李贻奎

期刊论文

FGF13 suppresses acute myeloid leukemia by regulating bone marrow niches

期刊论文

自体骨髓干细胞移植与归元方联用治疗急慢性肝损伤实验研究

吴理茂,李连达,刘红,宁可永,李贻奎

期刊论文

Everyone has a donor: contribution of the Chinese experience to global practice of haploidentical hematopoieticstem cell transplantation

Meng Lv, Yingjun Chang, Xiaojun Huang

期刊论文

Pluripotent stem cells exhibiting similar characteristics can be isolated from human fetal bone marrow

FANG Baijun, SONG Yongping, LIN Quande, ZHAO Chunhua, SHI Mingxia

期刊论文

大鼠骨髓间质干细胞的分离纯化与鉴定

张荣利,冯　雪,张会亮,罗国安,李连达,王义明

期刊论文

the intensity and loading time of direct current electric field on the directional migration of rat bonemarrow mesenchymal stem cells

null

期刊论文

Positive stool culture could predict the clinical outcomes of haploidentical hematopoietic stem celltransplantation

Lijuan Hu, Qi Wang, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Kaiyan Liu, Hui Wang, Xiaojun Huang, Xiaodong Mo

期刊论文

Comparison of reference values for immune recovery between event-free patients receiving haploidentical

null

期刊论文

Toll-like receptor signaling in hematopoietic homeostasis and the pathogenesis of hematologic diseases

null

期刊论文

疾病危险度-共患病指数在单倍型造血干细胞移植中的应用

莫晓冬, 张晓辉, 许兰平, 王昱, 闫晨华, 陈欢, 陈育红, 韩伟, 王峰蓉, 王景枝, 刘开彦, 黄晓军

期刊论文

Risk factors for chronic graft-versus-host disease after anti-thymocyte globulin-based haploidenticalhematopoietic stem cell transplantation in acute myeloid leukemia

Meng Lv, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Wei Han, Fengrong Wang, Jingzhi Wang, Kaiyan Liu, Xiaojun Huang, Xiaodong Mo

期刊论文

Hemophagocytic lymphohistiocytosis: critical reappraisal of a potentially under-recognized condition

null

期刊论文