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Triterpenoid inducers of Nrf2 signaling as potential therapeutic agents in sickle cell disease: a review

null

《医学前沿(英文)》 2015年 第9卷 第1期   页码 46-56 doi: 10.1007/s11684-015-0375-1

摘要:

Sickle cell disease (SCD) is an inherited disorder of hemoglobin in which the abnormal hemoglobin S polymerizes when deoxygenated. This polymerization of hemoglobin S not only results in hemolysis and vaso-occlusion but also precipitates inflammation, oxidative stress and chronic organ dysfunction. Oxidative stress is increasingly recognized as an important intermediate in these pathophysiological processes and is therefore an important target for therapeutic intervention. The transcription factor nuclear erythroid derived- 2 related factor 2 (Nrf2) controls the expression of anti-oxidant enzymes and is emerging as a protein whose function can be exploited with therapeutic intent. This review article is focused on triterpenoids that activate Nrf2, and their potential for reducing oxidative stress in SCD as an approach to prevent organ dysfunction associated with this disease. A brief overview of oxidative stress in the clinical context of SCD is accompanied by a discussion of several pathophysiological mechanisms contributing to oxidative stress. Finally, these mechanisms are then related to current management strategies in SCD that are either utilized currently or under evaluation. The article concludes with a perspective on the potential of the various therapeutic interventions to reduce oxidative stress and morbidity associated with SCD.

关键词: oxidative stress     Nrf2     triterpenoids     sickle cell disease     vaso-occlusion     CDDO-Me    

Dynamics of foot-and-mouth disease virus replication in cells at different phases of the cell-division

Claudia DOEL,Zhidong ZHANG,Lise MAZELET,Ryan WATERS,John BASHIRUDDIN

《农业科学与工程前沿(英文)》 2014年 第1卷 第3期   页码 250-257 doi: 10.15302/J-FASE-2014031

摘要: Foot-and-mouth-disease virus (FMDV) replicates in epithelial cells. The restriction of FMDV RNA to the basal cell layer of epithelia suggests a possible link between FMDV replication and the cell status. This paper describes studies in which FMDV infection was investigated in cells that were held at various cell division phases using cell cycle inhibitors. The results suggest that when cells were arrested at the G or G /S phase, high levels of viral RNA were detected by quantitative real-time reverse transcription PCR and viral protein synthesis was observed by specific labeling techniques. In contrast, when cells were arrested at the G /M phase, reduced or no viral RNA synthesis was detected.

关键词: foot-and-mouth disease virus     cell cycle     replication    

Therapeutic potential of stem cell in liver regeneration

null

《医学前沿(英文)》 2011年 第5卷 第1期   页码 26-32 doi: 10.1007/s11684-011-0107-0

摘要:

Liver transplantation is the only life-saving procedure for patients with end-stage liver disease. However, its potential benefits are hampered by many disadvantages, such as the relative shortage of donors, operative risks, and high costs. These issues have prompted the search for new alternative therapies for irreversible liver disease. Stem cell therapy, with the ability for self-renewal and potential for multilineage differentiation, is a promising alternative approach. Several studies have demonstrated that transplantation of hepatic stem/progenitor cells or hepatocyte-like cells derived from multipotent stem cells leads to donor cell-mediated repopulation of the liver and improved survival rates in experimental models of liver disease. However, a registered clinical application based on stem cell technology will take at least an additional 5 to 10 years because of some limitations; e.g. the lack of suitable cell sources and risk of teratoma formation. This review summarizes the general understanding of the therapeutic potentials of stem cells in liver disease, including the sources, mechanisms, and delivery methods of hepatic stem cells in liver regeneration, and discusses some challenges for their therapeutic application.

关键词: stem cell     liver disease     regenerative medicine    

Diffuse cystic lung diseases

null

《医学前沿(英文)》 2013年 第7卷 第3期   页码 316-327 doi: 10.1007/s11684-013-0269-z

摘要:

Diffuse cystic lung diseases are uncommon but can present a diagnostic challenge because increasing number of diseases have been associated with this presentation. Cyst in the lung is defined as a round parenchymal lucency with a well-defined thin wall (<2 mm thickness). Focal or multifocal cystic lesions include blebs, bullae, pneumatoceles, congenital cystic lesions, traumatic lesions, and several infectious processes such as coccidioidomycosis, Pneumocystis jiroveci pneumonia, and hydatid disease. “Diffuse” distribution in the lung implies involvement of all lobes. Diffuse lung involvement with cystic lesions can be seen in pulmonary lymphangioleiomyomatosis, pulmonary Langerhans’ cell histiocytosis, lymphoid interstitial pneumonia, Birt-Hogg-Dubé syndrome, amyloidosis, light chain deposition disease, honeycomb lung associated with advanced fibrosis, and several other rare causes including metastatic disease. High-resolution computed tomography of the chest helps define morphologic features of the lung lesions as well as their distribution and associated features such as intrathoracic lymphadenopathy. Correlating the tempo of the disease process and clinical context with chest imaging findings serve as important clues to defining the underlying nature of the cystic lung disease and guide diagnostic evaluation as well as management.

关键词: cyst     lung disease     interstitial lung disease     lymphangioleiomyomatosis     Langerhans’ cell histiocytosis     Birt-Hogg-Dubé syndrome    

Long non-coding RNA SAP30-2:1 is downregulated in congenital heart disease and regulates cell proliferation

Jing Ma, Shiyu Chen, Lili Hao, Wei Sheng, Weicheng Chen, Xiaojing Ma, Bowen Zhang, Duan Ma, Guoying Huang

《医学前沿(英文)》 2021年 第15卷 第1期   页码 91-100 doi: 10.1007/s11684-020-0778-5

摘要: Congenital heart disease (CHD) is the most common birth defect worldwide. Long non-coding RNAs (lncRNAs) have been implicated in many diseases. However, their involvement in CHD is not well understood. This study aimed to investigate the role of dysregulated lncRNAs in CHD. We used Gene Expression Omnibus data mining, bioinformatics analysis, and analysis of clinical tissue samples and observed that the novel lncRNA SAP30-2:1 with unknown function was significantly downregulated in damaged cardiac tissues from patients with CHD. Knockdown of lncRNA SAP30-2:1 inhibited the proliferation of human embryonic kidney and AC16 cells and decreased the expression of heart and neural crest derivatives expressed 2 (HAND2). Moreover, lncRNA SAP30-2:1 was associated with HAND2 by RNA immunoprecipitation. Overall, these results suggest that lncRNA SAP30-2:1 may be involved in heart development through affecting cell proliferation via targeting HAND2 and may thus represent a novel therapeutic target for CHD.

关键词: congenital heart disease     Gene Expression Omnibus     lncRNA SAP30-2:1     cell proliferation     RNA immunoprecipitation     HAND2    

patients with acute leukemia/myelodysplastic syndrome with unsatisfactory response to minimal residual disease-directeddonor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation

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

《医学前沿(英文)》 2019年 第13卷 第2期   页码 238-249 doi: 10.1007/s11684-017-0599-3

摘要: The efficacy of salvage interferon-α (IFN-α) treatment was investigated in patients with unsatisfactory response to minimal residual disease (MRD)-directed donor lymphocyte infusion (DLI) ( =24). Patients who did not become MRD-negative at 1 month after DLI were those with unsatisfactory response and were eligible to receive salvage IFN-α treatment within 3 months of DLI. Recombinant human IFN-α-2b injections were subcutaneously administered 2–3 times a week for 6 months. Nine (37.5%), 6 (25.0%), and 3 (12.5%) patients became MRD-negative at 1, 2, and>2 months after the salvage IFN-α treatment, respectively. Two-year cumulative incidences of relapse and non-relapse mortality were 35.9% and 8.3%, respectively. Two-year probabilities of event-free survival, disease-free survival, and overall survival were 51.6%, 54.3%, and 68.0%, respectively. Outcomes of patients subjected to salvage IFN-α treatment after DLI were significantly better than those with persistent MRD without IFN-α treatment. Moreover, clinical outcomes were comparable between the salvage DLI and IFN-α treatment groups. Thus, salvage IFN-α treatment may help improve the outcome of patients with unsatisfactory responses to MRD-directed DLI and could be a potential salvage treatment for these patients after allogeneic hematopoietic stem cell transplantation.

关键词: interferon-α     hematopoietic stem cell transplantation     minimal residual disease     donor lymphocyte infusion    

donor: contribution of the Chinese experience to global practice of haploidentical hematopoietic stem cell

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    

Minimal residual disease-directed immunotherapy for high-risk myelodysplastic syndrome after allogeneichematopoietic stem cell transplantation

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

《医学前沿(英文)》 2019年 第13卷 第3期   页码 354-364 doi: 10.1007/s11684-018-0665-5

摘要: The efficacy of minimal residual disease (MRD)-directed immunotherapy, including interferon- (IFN- ) treatment and chemotherapy plus granulocyte colony-stimulating factor-primed donor leukocyte infusion (chemo-DLI), was investigated in patients with high-risk myelodysplastic syndrome (MDS) who were MRD-positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT). High-risk MDS patients who received non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology and were MRD-positive after allo-HSCT were studied ( =47). The MRD-positive status was considered if leukemia-associated aberrant immune phenotypes or Wilms’ tumor gene 1 expression is present in a single bone marrow sample. The cumulative incidence of the relapse and non-relapse mortality 2 years after immunotherapy were 14.5% and 21.4% ( =0.377) and 9.1% and 0.0% ( =0.985) for patients in the IFN- and chemo-DLI groups, respectively. The probability of disease-free and overall survival 2 years after immunotherapy were 76.4% and 78.6% ( =0.891) and 84.3% and 84.6% ( =0.972) for patients in the IFN- and chemo-DLI groups, respectively. Persistent MRD after immunotherapy was associated with poor survival. Thus, the MRD-directed immunotherapy was effective for patients with high-risk MDS who were MRD-positive after allo-HSCT, and the efficacy was comparable between chemo-DLI and IFN- treatment.

关键词: donor leukocyte infusion     hematopoietic stem cell transplantation     interferon-   

Utility of transbronchial biopsy in the diagnosis of lymphangioleiomyomatosis

null

《医学前沿(英文)》 2012年 第6卷 第4期   页码 395-405 doi: 10.1007/s11684-012-0231-5

摘要:

Pulmonary lymphangioleiomyomatosis (LAM) is a rare cystic lung disease that targets women during their reproductive years. A confident diagnosis can often be based on clinical grounds, but diagnostic certainty requires pathological analysis. Although surgical lung biopsy is considered the gold standard for obtaining tissue in patients with diffuse lung disease, it is also associated with higher morbidity and mortality than alternative, less invasive techniques. The objective of our study was to examine the utility of transbronchial biopsy in the diagnosis of LAM. We conducted two online surveys of over 1 000 LAM patients registered with the LAM Foundation who were accessible by email. Transbronchial biopsy specimens were subsequently collected and reviewed by an expert pathologist to validate the diagnosis. We found that transbronchial biopsy has a yield of approximately 60% in patients with LAM. We conclude that transbronchial biopsy may be a safe and effective method for establishing the diagnosis of LAM, obviating the need for surgical lung biopsy in more than half of LAM patients.

关键词: lymphangioleiomyomatosis     lymphangiomyomatosis     multicystic lung disease     diffuse cystic lung disease     transbronchial biopsy     perivascular epithelioid cell tumor (PEComa)     HMB-45    

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    

White blood cell count and the incidence of hyperuricemia: insights from a community-based study

Jian Liu, Pingyan Shen, Xiaobo Ma, Xialian Yu, Liyan Ni, Xu Hao, Weiming Wang, Nan Chen

《医学前沿(英文)》 2019年 第13卷 第6期   页码 741-746 doi: 10.1007/s11684-017-0579-7

摘要: Hyperuricemia (HUA) is a risk factor for chronic kidney disease (CKD). The relationship between HUA and white blood cell (WBC) count remains unknown. A sampling survey for CKD was conducted in Sanlin community in 2012 and 2014. CKD was defined as proteinuria in at least the microalbuminuric stage or an estimated GFR of 60 mL/(min·1.73 m ). HUA was defined as serum uric acid>420 µmol/L in men and>360 µmol/L in women. This study included 1024 participants. The prevalence of HUA was 17.77%. Patients with HUA were more likely to have higher levels of WBC count, which was positively associated with HUA prevalence. This association was also observed in participants without CKD, diabetes mellitus, hyperlipidemia, or obesity. Multivariate logistic regression analysis showed that WBC count was independently associated with the risk for HUA in male and female participants. Compared with participants without HUA, inflammatory factors such as high-sensitivity C-reactive protein, tumor necrosis factor-α and interleukin 6 increased in participants with HUA. Hence, WBC count is positively associated with HUA, and this association is independent of conventional risk factors for CKD.

关键词: white blood cell count     hyperuricemia     chronic kidney disease     inflammation    

细胞治疗开创疾病干预新纪元

吕凌,田志刚,王学浩

《工程(英文)》 2019年 第5卷 第1期   页码 3-4 doi: 10.1016/j.eng.2019.01.004

and protein expression of proteinase-activated receptor-1, 2 in a murine model of acute graft host disease

Quan LI MD , Weiming LI MD , Ping ZOU MD , Jian ZHANG BM ,

《医学前沿(英文)》 2009年 第3卷 第3期   页码 309-315 doi: 10.1007/s11684-009-0043-4

摘要: Proteinase-activated receptors (PARs) are a novel subclass of seven transmembrane-spanning, G protein-coupled receptors. PAR-1 and PAR-2 are widely expressed in a variety of cells and are found to be involved in many physiological and pathological processes including inflammation and immune response. However, little is known about the function of PAR-1, 2 in acute graft host disease (GVHD). In the present study, we first detected the expression of PAR-1, 2 protein and mRNA in a murine model of acute GVHD using the methods of immunohistochemistry, Western blot and quantitative real-time polymerase chain reaction (PCR). Syngeneic hematopoietic stem cell transplantation (HSCT) mice served as controls. The relative gene expression level of PAR-1 was significantly increased in the skin, liver, small intestine of allogeneic HSCT mice (in skin: 0.039±0.013 0.008±0.002 of controls, =0.009; in liver: 0.165±0.006 0.017±0.006 of controls, =0.004; in small intestine: 0.215±0.009 0.016±0.002 of controls, =0.003), but not in the stomach, lung and kidney of allogeneic HSCT mice (>0.05). PAR-2 mRNA expression in the liver and small intestine of allogeneic HSCT mice (in liver: 0.010±0.002 0.003±0.001 of controls, =0.008; in small intestine: 0.006±0.001 0.003±0.001 of controls, =0.024) was increased significantly, but PAR-2 mRNA expression in the other organs (>0.05) was not found to be significantly elevated. PAR-1, 2 protein expression was in accordance with the mRNA expression, as shown by Western blot. Using immunohistochemistry the present study demonstrated that there was strong PAR-1, 2 immunoreactivity in the epithelial cell and vascular endothelial cell of target organs of acute GVHD. Our findings of markedly increased expression of PAR-1, 2 in target organs of acute GVHD suggest that PAR-1 and PAR-2 may play an important role in the pathogenesis of acute GVHD.

关键词: graft vs host disease     proteinase-activated receptor     murine model     hematopoietic stem cell transplantation    

免疫调节细胞生物学及其在急性移植物抗宿主病预防或治疗中的临床应用 Review

Bruce R. Blazar

《工程(英文)》 2019年 第5卷 第1期   页码 98-105 doi: 10.1016/j.eng.2018.11.016

摘要:

预防和治疗移植物抗宿主病(GVHD)最常见的方法是尝试耗竭或抑制能介导或支持同种异体反应的T细胞;但这会导致T细胞受体功能缺陷,并因此对感染和肿瘤复发高度敏感。通常通过广泛使用反应性抗体来实现耗竭,而功能损坏通常在使用需长期给药(一般为6个月或更长时间)且具有明显副作用的药物后发生,这种药物可能不会导致供体T细胞对耐调节方案且携带宿主同种抗原的细胞产生耐受性(即无反应性)。随着对免疫系统稳态认识的深化,我们已能鉴定和表征具有免疫调节功能的细胞群。虽然这种细胞群通常比较少见,但可通过分离和扩增此类细胞的方法在移植后晚期增补供体移植物或进行输注,来抑制GVHD。本文将探讨GVHD模型中的生物学和临床前概念验证,以及现已发展至临床测试阶段的免疫调节细胞疗法对GVHD的疗效。

关键词: 移植物抗宿主病(GVHD)     免疫调节细胞     细胞疗法    

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)患者的疾病危险度-共患病指数(disease risk comorbidity index, DRCI)。文中通过一个训练队列(n = 593)中确定了无疾病生存(disease-free survival, DFS)的预测因素,然后对这些因素进行赋值,从而建立DRCI,并通过验证队列(<

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    

标题 作者 时间 类型 操作

Triterpenoid inducers of Nrf2 signaling as potential therapeutic agents in sickle cell disease: a review

null

期刊论文

Dynamics of foot-and-mouth disease virus replication in cells at different phases of the cell-division

Claudia DOEL,Zhidong ZHANG,Lise MAZELET,Ryan WATERS,John BASHIRUDDIN

期刊论文

Therapeutic potential of stem cell in liver regeneration

null

期刊论文

Diffuse cystic lung diseases

null

期刊论文

Long non-coding RNA SAP30-2:1 is downregulated in congenital heart disease and regulates cell proliferation

Jing Ma, Shiyu Chen, Lili Hao, Wei Sheng, Weicheng Chen, Xiaojing Ma, Bowen Zhang, Duan Ma, Guoying Huang

期刊论文

patients with acute leukemia/myelodysplastic syndrome with unsatisfactory response to minimal residual disease-directeddonor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation

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

期刊论文

donor: contribution of the Chinese experience to global practice of haploidentical hematopoietic stem cell

Meng Lv, Yingjun Chang, Xiaojun Huang

期刊论文

Minimal residual disease-directed immunotherapy for high-risk myelodysplastic syndrome after allogeneichematopoietic stem cell transplantation

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

期刊论文

Utility of transbronchial biopsy in the diagnosis of lymphangioleiomyomatosis

null

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

White blood cell count and the incidence of hyperuricemia: insights from a community-based study

Jian Liu, Pingyan Shen, Xiaobo Ma, Xialian Yu, Liyan Ni, Xu Hao, Weiming Wang, Nan Chen

期刊论文

细胞治疗开创疾病干预新纪元

吕凌,田志刚,王学浩

期刊论文

and protein expression of proteinase-activated receptor-1, 2 in a murine model of acute graft host disease

Quan LI MD , Weiming LI MD , Ping ZOU MD , Jian ZHANG BM ,

期刊论文

免疫调节细胞生物学及其在急性移植物抗宿主病预防或治疗中的临床应用

Bruce R. Blazar

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