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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    

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    

Graft versus host disease after liver transplantation: A case report

Peng-Ji GAO, Xi-Sheng LENG, Dong WANG, Guang-Ming LI, Lei HUANG, Jie GAO, JI-Ye ZHU,

《医学前沿(英文)》 2010年 第4卷 第4期   页码 469-472 doi: 10.1007/s11684-010-0120-8

摘要: In documenting clinical experience in the diagnosis and treatment of graft host disease (GVHD), we retrospectively analyzed data of one case that has developed GVHD after liver transplantation. This patient exhibited fever, skin rash, and diarrhea on day 9 after liver transplantation. His liver function was normal. Skin biopsy showed scattered keratinocytes accompanied by satellite-like lymphocyte infiltration and basal cell liquefaction degeneration. After carefully analyzing the complications, we took the strategy of decreasing the dose of tacrolimus. Thereafter, the patient’s temperature decreased to normal, his skin rashes subsided, and his diarrhea was relieved. This case suggests that reducing the dosage of immunosuppressive agents can be an effective strategy for GVHD after liver transplantation.

关键词: liver transplantation     graft versus host disease    

Everyone has a donor: contribution of the Chinese experience to global practice of haploidentical hematopoietic stem 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    

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

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    

Molecular pathogenesis of acute myeloid leukemia: A diverse disease with new perspectives

Felicitas THOL, Arnold GANSER

《医学前沿(英文)》 2010年 第4卷 第4期   页码 356-362 doi: 10.1007/s11684-010-0220-5

摘要: Acute myeloid leukemia (AML) is a very heterogeneous neoplasm of the hematopoietic stem cell. Despite important achievements in the treatment of AML, the long term survival of patients with the disease remains poor. Understanding the pathogenesis of AML better is crucial for finding new treatment approaches. During AML development hematopoietic precursor cells undergo clonal transformation in a multistep process through acquisition of chromosomal rearrangements and/or different gene mutations. Over recent years, novel gene mutations have been found in patients with AML. These mutations can be divided into two important categories, class I mutations that confer a proliferation advantage and class II mutations that inhibit myeloid differentiation. Screening for some of these mutations is now part of the initial diagnostic work-up in newly diagnosed AML patients. Information about the mutation status of specific genes is useful for risk-stratification, minimal residual disease (MRD) monitoring and increasingly also for targeted therapy, especially for patients with cytogenetically normal AML (CN-AML). Besides chromosomal rearrangements and gene mutations, epigenetic regulation of genes – meaning changes in gene expression by mechanisms other than changes in the underlying DNA sequence – also represents an important mechanism of leukemogenesis. This article reviews some of the most common mutations in CN-AML and gives a perspective of the translation of these discoveries from bench to bedside.

关键词: acute myeloid leukemia     mutations     risk stratification    

Interferon-α salvage treatment is effective for patients with acute leukemia/myelodysplastic syndromewith unsatisfactory response to minimal residual disease-directed donor lymphocyte infusion after allogeneic

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    

Robotic distal pancreatectomy versus conventional laparoscopic distal pancreatectomy: a comparative study

null

《医学前沿(英文)》 2015年 第9卷 第3期   页码 356-360 doi: 10.1007/s11684-015-0404-0

摘要:

Robotic system has been increasingly used in pancreatectomy. However, the effectiveness of this method remains uncertain. This study compared the surgical outcomes between robot-assisted laparoscopic distal pancreatectomy and conventional laparoscopic distal pancreatectomy. During a 15-year period, 35 patients underwent minimally invasive approach of distal pancreatectomy in our center. Seventeen of these patients had robot-assisted laparoscopic approach, and the remaining 18 had conventional laparoscopic approach. Their operative parameters and perioperative outcomes were analyzed retrospectively in a prospective database. The mean operating time in the robotic group (221.4 min) was significantly longer than that in the laparoscopic group (173.6 min) (P = 0.026). Both robotic and conventional laparoscopic groups presented no significant difference in spleen-preservation rate (52.9% vs. 38.9%) (P = 0.505), operative blood loss (100.3 ml vs. 268.3 ml) (P = 0.29), overall morbidity rate (47.1% vs. 38.9%) (P = 0.73), and post-operative hospital stay (11.4 days vs. 14.2 days) (P = 0.46). Both groups also showed no perioperative mortality. Similar outcomes were observed in robotic distal pancreatectomy and conventional laparoscopic approach. However, robotic approach tended to have the advantages of less blood loss and shorter hospital stay. Further studies are necessary to determine the clinical position of robotic distal pancreatectomy.

关键词: distal pancreatectomy     pancreatic neoplasm     robotic surgery    

Performance and synergistic effect of phenolic and thio antioxidants in ABS graft copolymers

Gongsheng LI, Xuhong GUO, Wang NA, Diancheng HAO, Mingyao ZHANG, Huixuan ZHANG, Jun XU

《化学科学与工程前沿(英文)》 2011年 第5卷 第1期   页码 26-34 doi: 10.1007/s11705-010-0531-8

摘要: The synergistic effect of phenolic and thio antioxidants on the stabilization of acrylonitrile-butadiene-styrene (ABS) graft copolymers has been studied. Three commercial antioxidants Irganox245, Irganox1076 and dilauryl thiodipropionate (DLTP) were selected. Formulations based on hindered phenols and secondary antioxidant DLTP were prepared. Stabilization was monitored in terms of changes in the functional groups (oxidation products), tensile properties and yellowness index. Differential scanning calorimetry (DSC) and thermogravimetry (TG) were also used to assess the stability. The results indicated that the combination of Irganox245 and DLTP showed much better stabilization effect than the individual components due to the strong synergistic effect. Only weak synergism could be observed in the formulation that contained Irganox1076 and DLTP. Irganox1076 and Irgnox1076/DLTP exhibited similar behaviors between antioxidants with the highest and lowest efficiencies.

关键词: antioxidant     ABS graft copolymers     synergistic effect    

巨噬细胞在器官移植急性排斥反应中的双重作用 Review

谭亮, 郭易难, 冯畅, 侯仰潇, 谢续标, 赵勇

《工程(英文)》 2022年 第10卷 第3期   页码 21-29 doi: 10.1016/j.eng.2021.10.015

摘要:

天然免疫细胞在移植免疫反应中发挥着重要作用。巨噬细胞是重要的天然免疫细胞;在发生排斥反应的同种异基因移植器官中,巨噬细胞也是浸润的众多免疫细胞之一。巨噬细胞的浸润与器官移植的短期和长期效果呈负相关。在功能方面,巨噬细胞具有异质性和可塑性。在器官移植排斥反应中,巨噬细胞可以为适应性免疫提呈同种异基因抗原以及提供共刺激信号和细胞因子,也可以直接损伤移植器官。此外,一些具有免疫调节功能的巨噬细胞亚群,可以通过抑制排斥反应和促进免疫耐受来保护移植器官。尽管目前研究人员已认识到巨噬细胞在移植器官损伤过程中的潜在作用,但他们对巨噬细胞在移植排斥反应中的不同作用关注不够。为此,本文就巨噬细胞在急性移植免疫反应中的独特作用以及免疫抑制剂对巨噬细胞的影响进行了综述和讨论。通过分析发现,对于巨噬细胞在移植免疫中的作用的相关研究中,应更多地关注其复杂性和关键功能,并应更多地致力于开发针对巨噬细胞的免疫抑制药物,并使之有利于提高移植器官的长期存活率和移植免疫耐受的建立。

关键词: 巨噬细胞     移植     耐受     排斥反应     调节性巨噬细胞    

间充质干细胞——新冠病毒肺炎相关急性呼吸窘迫综合征潜在的治疗选择

赵璇, 张毅

《工程(英文)》 2020年 第6卷 第10期   页码 1073-1075 doi: 10.1016/j.eng.2020.05.015

Separation of epigallocatechin-3-gallate from crude tea polyphenols by using Cellulose diacetate graft

Hong ZHU, Peiyong QIN

《化学科学与工程前沿(英文)》 2011年 第5卷 第3期   页码 330-338 doi: 10.1007/s11705-010-1104-6

摘要: This study demonstrates a new Cellulose diacetate graft -cyclodextrin (CDA- -CD) copolymer asymmetric membrane prepared by a phase inversion technique for the separation of (-)-epigallocatechin-3-gallate (EGCG) from other polyphenols in crude tea. The graft copolymer, CDA- -CD, was synthesized by prepolymerization of cellulose diacetate (CDA) and 1,6-hexamethylene-diisocyanate (HDI), which was then grafted with -cyclodextrin ( -CD). Surface and cross-section morphologies of the CDA- -CD membranes were analyzed by using scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FT-IR) indicated that the -CD was grafted onto the CDA by chemical bonding. The influences of the HDI/CDA mass ratio and the catalyst mass fraction on the -CD graft yield were investigated. The optimum conditions of a HDI/CDA mass ratio of 0.35 g·g and a catalyst mass fraction of 0.18 wt-% produced a -CD graft yield of 26.51 wt-%. The effects of the -CD graft yield and the concentration of the polymer cast solution on the separation of EGCG were also investigated. Under optimum conditions of a -CD graft yield of 24.21 wt-% and a polymer concentration of 13 wt-%, the purity of EGCG increased from 26.51 to 86.91 wt-%.

关键词: (-)-epigallocatechin-3-gallate (EGCG)     tea polyphenols     CDA-β-CD    

AMMONIA DISPERSION FROM MULTI-FLOOR VERSUS STANDARD SINGLE-FLOOR PIG PRODUCTION FACILITIES BASED ON COMPUTATIONAL

《农业科学与工程前沿(英文)》 2023年 第10卷 第3期   页码 374-389 doi: 10.15302/J-FASE-2023501

摘要:

● NH3 dispersion from a multi-floor pig building was compared to a single-floor building.

关键词: pig building     computational fluid dynamics     ammonia     dispersion    

Integrated analysis of gut microbiome and host immune responses in COVID-19

《医学前沿(英文)》 2022年 第16卷 第2期   页码 263-275 doi: 10.1007/s11684-022-0921-6

摘要: Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases. Here, to explore the role of the gut microbiome in the host immune responses in COVID-19, we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples. We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones. We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity, such as Enterococcus faecium, Coprococcus comes, Roseburia intestinalis, Akkermansia muciniphila, Bacteroides cellulosilyticus and Blautia obeum. We further analyzed the correlation between the abundance of gut microbes and host responses, and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe, including Coprococcus comes that was positively correlated with CD3+/CD4+/CD8+ lymphocyte counts. In addition, an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells (PBMCs) showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples. Moreover, a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases, including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19. Together, our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.

关键词: COVID-19     SARS-COV-2     gut microbiome     immune response    

Clinical characteristics of 19 neonates born to mothers with COVID-19

Wei Liu, Jing Wang, Wenbin Li, Zhaoxian Zhou, Siying Liu, Zhihui Rong

《医学前沿(英文)》 2020年 第14卷 第2期   页码 193-198 doi: 10.1007/s11684-020-0772-y

摘要: The aim of this study was to investigate the clinical characteristics of neonates born to SARS-CoV-2 infected mothers and increase the current knowledge on the perinatal consequences of COVID-19. Nineteen neonates were admitted to Tongji Hospital from January 31 to February 29, 2020. Their mothers were clinically diagnosed or laboratory-confirmed with COVID-19. We prospectively collected and analyzed data of mothers and infants. There are 19 neonates included in the research. Among them, 10 mothers were confirmed COVID-19 by positive SARS-CoV-2 RT-PCR in throat swab, and 9 mothers were clinically diagnosed with COVID-19. Delivery occurred in an isolation room and neonates were immediately separated from the mothers and isolated for at least 14 days. No fetal distress was found. Gestational age of the neonates was 38.6±1.5 weeks, and average birth weight was 3293±425 g. SARS-CoV-2 RT-PCR in throat swab, urine, and feces of all neonates were negative. SARS-CoV-2 RT-PCR in breast milk and amniotic fluid was negative too. None of the neonates developed clinical, radiologic, hematologic, or biochemical evidence of COVID-19. No vertical transmission of SARS-CoV-2 and no perinatal complications in the third trimester were found in our study. The delivery should occur in isolation and neonates should be separated from the infected mothers and care givers.

关键词: coronavirus disease 2019     severe acute respiratory syndrome-associated coronavirus     maternal-infant infection     newborn    

标题 作者 时间 类型 操作

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

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

Graft versus host disease after liver transplantation: A case report

Peng-Ji GAO, Xi-Sheng LENG, Dong WANG, Guang-Ming LI, Lei HUANG, Jie GAO, JI-Ye ZHU,

期刊论文

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

Meng Lv, Yingjun Chang, Xiaojun Huang

期刊论文

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

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

期刊论文

Molecular pathogenesis of acute myeloid leukemia: A diverse disease with new perspectives

Felicitas THOL, Arnold GANSER

期刊论文

Interferon-α salvage treatment is effective for patients with acute leukemia/myelodysplastic syndromewith unsatisfactory response to minimal residual disease-directed donor lymphocyte infusion after allogeneic

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

Robotic distal pancreatectomy versus conventional laparoscopic distal pancreatectomy: a comparative study

null

期刊论文

Performance and synergistic effect of phenolic and thio antioxidants in ABS graft copolymers

Gongsheng LI, Xuhong GUO, Wang NA, Diancheng HAO, Mingyao ZHANG, Huixuan ZHANG, Jun XU

期刊论文

巨噬细胞在器官移植急性排斥反应中的双重作用

谭亮, 郭易难, 冯畅, 侯仰潇, 谢续标, 赵勇

期刊论文

间充质干细胞——新冠病毒肺炎相关急性呼吸窘迫综合征潜在的治疗选择

赵璇, 张毅

期刊论文

Separation of epigallocatechin-3-gallate from crude tea polyphenols by using Cellulose diacetate graft

Hong ZHU, Peiyong QIN

期刊论文

AMMONIA DISPERSION FROM MULTI-FLOOR VERSUS STANDARD SINGLE-FLOOR PIG PRODUCTION FACILITIES BASED ON COMPUTATIONAL

期刊论文

Integrated analysis of gut microbiome and host immune responses in COVID-19

期刊论文

Clinical characteristics of 19 neonates born to mothers with COVID-19

Wei Liu, Jing Wang, Wenbin Li, Zhaoxian Zhou, Siying Liu, Zhihui Rong

期刊论文