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Distribution and differentiation of myeloid-derived suppressor cells after fluid resuscitation in mice with hemorrhagic shock

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2017年第1期18卷 48-58页

作者： Jiu-kun JIANG Wen FANG Liang-jie HONG Yuan-qiang LU Department of Emergency Medicine the First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China key laboratory of combined multi-organ transplantation the First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China

Objective： To investigate the distribution and differentiation of myeloid-derived suppressor cells （MDSCs） in hemorrhagic shock mice, which are resuscitated with normal saline （NS）, hypertonic saline （HTS）, and hydroxyethyl starch （HES）. Methods： BALB/c mice were randomly divided into control, NS, HTS, and HES resuscitation groups. Three subgroups （n=8） in each resuscitation group were marked as 2, 24, and 72 h. Flow cytometry was used to detect the MDSCs, monocytic MDSCs （M-MDSCs）, and granulocytic/neutrophilic MDSCs （G-MDSCs） in peripheral blood nucleated cells （PBNCs）, spleen single-cell suspension, and bone marrow nucleated cells （BMNCs）. Results： The MDSCs in BMNCs among three resuscitation groups were lower 2 h after shock, in PBNCs of the HTS group were higher, and in spleen of the NS group were lower （all P〈0.05 vs. control）. The M-MDSC/G-MDSC ratios in PBNCs of the HTS and HES groups were lower （both ,P〈0.05 vs. control）. At 24 h, the MDSCs in PBNCs of the NS and HTS groups were higher, while the spleen MDSCs in the HTS group were higher （all P〈0.05 vs. control）. The M-MDSC/ G-MDSC ratios were all less in PBNCs, spleen, and BMNCs of the NS and HTS groups, and were lower in BMNCs of the HES group （all P〈0.05 vs. control）. At 72 h, the elevated MDSCs in PBNCs were presented in the HTS and HES groups, and in spleen the augment turned up in three resuscitation groups （all P〈0.05 vs. control）. The inclined ratios to M-MDSC were exhibited in spleen of the NS and HTS groups, and in PBNCs of the NS group; the inclination to G-MDSC in BMNCs was shown in the HES group （all P〈0.05 vs. control）. Conclusions： HTS induces the earlier ele- vation of MDSCs in peripheral blood and spleen, and influences its distribution and differentiation, while HES has a less effect on the distribution but a stronger impact on the differentiation of MDSCs, especially in bone marrow.

关键词： Hemorrhagic shock Hydroxyethyl starch Hypertonic saline Myeloid-derived suppressor cells Normal saline

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Molecular subtyping of hepatocellular carcinoma:A step toward precision medicine

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Cancer Communications 2020年第12期40卷 681-693页

作者： Yichao Wu Zhikun Liu Xiao Xu Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouZhejiang 310006P.R.China national health commission key laboratory of combined multi-organ transplantation HangzhouZhejiang 310003P.R.China Institute of organ transplantationZhejiang University HangzhouZhejiang 310003P.R.China

Hepatocellular carcinoma(HCC)is one of the most prevalent and fatal digestive *** for this disease has been constraint by heterogeneity of this group of tumors,which has greatly limited the progress in personalized *** existing studies have revealed the genetic and epigenetic blueprints that drive HCCs,many of the molecular mechanisms that lead to HCCs remain *** advances in techniques for studying functional genomics,such as genome sequencing and transcriptomic analyses,have led to the discovery of molecular mechanisms that participate in the initiation and evolution of *** multi-omics analyses have identified several molecular subtypes of HCC associated with specific molecular characteristics and clinical *** similar molecular features among highly heterogeneous HCC patients is a prerequisite to implementation of personalized *** review summarizes the current research progresses in precision therapy on the backbone of molecular subtypes of HCC.

关键词： hepatocellular carcinoma immune subtype molecular subtyping multi-omics subtype mutation subtype precision medicine proteomic subtype transcriptome genotype

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Changes of sphingolipids profiles after ischemia-reperfusion injury in the rat liver

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Chinese Medical Journal 2009年第24期122卷 3025-3031页

作者： ZHAI Shu-ting LIU Guang-yi XUE Fei SUN Gong-ping LIANG Liang CHEN Wei XU Guo-dong LI Jun-jian YANG Jun LIANG Ting-bo Department of Hepatobiliary and Pancreatic Surgery Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health First Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310003 China Department of Toxicology Zhejiang University School of PublicHealth Hangzhou Zhejiang 310031 China

Background Hepatic ischemia-reperfusion （I/R） injury occurs in many clinical procedures. The molecular mechanisms responsible for hepatic I/R injury however remain unknown. Sphingolipids, in particular ceramide, play a role in stress and death receptor-induced hepatocellular death, contributing to the progression of several liver diseases including liver I/R injury. In order to further define the role of sphingolipids in hepatic I/R, systemic analysis of sphingolipids after reperfusion is necessary. Methods We investigated the lipidomic changes of sphingolipids in a rat model of warm hepatic I/R injury, by delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry （DE MALDI-TOF-MS）. Results The total amounts of ceramide and sphingomyelin and the intensity of most kinds of sphingolipids, mainly sphingomyelin, significantly increased at 1 hour after reperfusion （P 〈0.05） and reached peaks at 6 hours after reperfusion （P 〈0.01） compared to controls. Six new forms of ceramide and sphingomyelins appeared 6 hours after reperfusion, they were （m/z） 537.8, 555.7, 567.7, 583.8, 683.5 and 731.4 respectively. A ceramide-monohexoside （m/z） 804.4 （CMH（d18：1C22：1＋Na）＋） also increased after reperfusion and correlated with extent of liver injury after reperfursion. Conclusions Three main forms of sphingolipids, ceramide, sphingomyelin and ceramide-monohexoside, are related to hepatic I/R injury and provide a new perspective in understanding the mechanisms responsible for hepatic I/R injury.

关键词： lipidomic sphingolipids liver ischemia-reperfusion matrix-assisted laser desorption ionizationtime-of-flight mass spectrometry

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Liver transplantation in Crigler-Najjar syndrome type I disease

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Hepatobiliary & Pancreatic Diseases International 2012年第5期11卷 545-548页

作者： Zhen-Hua Tu, De-Sheng Shang, Jin-Cai Jiang, Wu Zhang, Min Zhang, Wei-Lin Wang, Hai-Yan Lou,Shu-Sen Zheng Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, key laboratory of combined multi-organ transplantation, Ministry of Public health & key laboratory of organ transplantation of Zhejiang Province Department of Radiology,First Affiliated Hospital,Zhejiang University School of Medicine, Hangzhou 310003, China Division of Hepatobiliary and Pancreatic Surgery Department of Surgery First Affiliated Hospital Zhejiang University School of Medicine Key Laboratory of Combined Multi-Organ Transplantation Ministry of Public Health & Key Laboratory of Organ Transplantation of Zhejiang Province Hangzhou 310003 Hangzhou China Department of Radiology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 Hangzhou China

BACKGROUND: Crigler-Najjar syndrome type I (CNS I) is a very rare autosomal recessive inherited disease that liver transplantation can properly deal with. METHODS: We present one case of an 18-month-old child with CNS I diagnosed by clinical findings and genetic detecting LTx was performed 5 days after kernicterus broke out and neurological symptoms were successfully reversed. RESULT: Magnetic resonance imaging and magnetic resonance spectroscopy showed encouraging results that brain pathology had a trend to return to normal in 1-year follow-up, combined with electroencephalogram and motor development estimate studies. CONCLUSIONS: Liver transplantation can cure CNS I with reversible neurological symptoms to some extent in time Magnetic resonance spectroscopy may be a future option of predicting brain conditions and selecting suitable patients with CNS I for transplantation.

关键词： Crigler-Najjar liver transplantation inborn error of metabolism magnetic resonance imaging hyperbilirubinemia

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The time-dependent shift in the hepatic graft and recipient macrophage pool following liver transplantation

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Cellular & Molecular Immunology 2020年第4期17卷 412-414页

作者： Haitao Huang Xueyou Zhang Cheng Zhang Hui Chen Qi Ling Shusen Zheng Department of Surgery Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina key laboratory of combined multi-organ transplantation Ministry of Public HealthHangzhouChina

Liver transplantation(LT)provides a cure for various end-stage liver *** liver graft becomes the recipient’s new metabolic center,and donor genetics plays a potent role in the development of complications in the recipient,such as metabolic disorders1 and even tumor recurrence.2 Notably,both the donor’s3 and recipient’s genetics4 contributes significantly to intrahepatic complications(e.g.,liver fibrosis and de novo steatosis).Therefore,crosstalk between donor and recipient tissue remodels the architecture and homeostasis of the transplanted liver,which is still a great challenge to explore.

关键词： liver homeostasis donor

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Changes of gut bacteria and immune parameters in liver transplant recipients

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Hepatobiliary & Pancreatic Diseases International 2012年第1期11卷 40-50页

作者： Zhong-Wen Wu, Zong-Xin Ling, Hai-Feng Lu, Jian Zuo, Ji-Fang Sheng, Shu-Sen Zheng and Lan-Juan Li State key laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases key Lab of combined multiorgan transplantation, Ministry of Public health, key Lab of organ transplantation and Department of Hepatobiliary and Pancreatic Surgery , First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China State key laboratory for Diagnosis and Treatment of Infectious Diseases Department of Infectious Diseases Zhejiang University School of Medicine Hangzhou 310003 Hangzhou China key Lab of combined multi-organ transplantation Ministry of Public Health Key Lab of Organ Transplantation and Department of Hepatobiliary and Pancreatic Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 Hangzhou China

BACKGROUND: Liver transplantation is one of the most effective therapeutic options for patients with end-stage liver diseases, and gut microbiota is actively involved in potential infections in pretransplant and posttransplant patients. However, the diversity of gut microbiota and its relationship with the immune parameter of liver transplantation recipients are not well understood. METHODS: We collected fresh feces and blood samples from 190 participants in China from November 2004 to May 2008, including 28 healthy volunteers, 51 cirrhotic patients and 111 liver-transplanted patients. Six interesting gut bacteria, plasma endotoxin, serum cytokines (i.e., tumor necrosis factor alpha and interleukin-6) and fecal secretory IgA (SIgA) were investigated by real-time quantitative PCR, chromogenic limulus amoebocyte assay, sandwich-type enzyme-linked immunosorbent assay and radioimmunoassay, respectively. RESULTS: All Eubacteria, Bifidobacterium spp., Faecalibacterium prausnitzii and Lactobacillus spp. were significantly lower in the liver transplantation recipients while Enterobacteriaceae and Enterococcus spp. were significantly higher (Ptransplantation. Plasma endotoxin, interleukin-6 and fecal SIgA in cirrhotic patients increased significantly, but not in liver transplantation recipients. Plasma endotoxin and interleukin-6 were negatively correlated with all Eubacteria and the Bacteroides-Prevotella group, while tumor necrosis factor alpha was not significantly correlated with these six gut bacteria in cirrhotic ***: Our study demonstrates that abundant gut bacteria were altered significantly in both cirrhotic and liver transplantation patients, while plasma endotoxin and interleukin-6 increased remarkably in cirrhotic patients, showing significant correlations with gut microbiota. Interestingly, our data show a tendency fo

关键词： gut bacteria interleukin-6 tumor necrosis factor alpha fecal secretory IgA liver transplantation

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Glibenclamide pretreatment attenuates early hematoma expansion of warfarin-associated intracerebral hemorrhage in rats by alleviating perihematomal blood-brain barrier dysfunction

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Chinese Neurosurgical Journal 2024年第1期10卷 8-19页

作者： Zongwei Zeng Liang Liang Zhou Feng Peiwen Guo Xiaoke Hao Jishu Xian Hua Feng Yujie Chen Zhi Chen Department of Neurosurgery and State key laboratory of Trauma Burn and Combined InjurySouthwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Department of Neurosurgery The 945Th Hospital of PLAYaanSichuan Province 625099China Department of Rehabilitation Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Chongqing key laboratory of Precision Neuromedicine and Neuroregeneration Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Chongqing Clinical Research Center for Neurosurgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China

Background Hematoma expansion is a determinant of poor outcome of intracerebral hemorrhage but occurs frequently,especially in warfarin-associated intracerebral hemorrhage(W-ICH).In the present study,we employ the warfarin-associated intracerebral hemorrhage(W-ICH)rat model,to explore the efficacy and potential mechanism of glibenclamide pretreatment on hematoma expansion after intracerebral hemorrhage,hoping to provide proof of concept that glibenclamide in stroke primary and secondary prevention is also potentially beneficial for intracerebral hemorrhage patients at early *** In the present study,we tested whether glibenclamide,a common hypoglycemic drug,could attenuate hematoma expansion in a rat model of *** expansion was evaluated using magnetic resonance imaging;brain injury was evaluated by brain edema and neuronal death;and functional outcome was evaluated by neurological *** blood-brain barrier integrity was assessed using Evans blue extravasation and tight junction-related *** The data indicated that glibenclamide pretreatment significantly attenuated hematoma expansion at 24 h after W-ICH,thus mitigating brain edema and neuronal death and promoting neurological function recovery,which may benefit from alleviating blood-brain barrier disruption by suppressing matrix *** The results indicate that glibenclamide pretreatment in stroke primary and secondary prevention might be a promising therapy for hematoma expansion at the early stage of W-ICH.

关键词： Intracerebral hemorrhage Warfarin Glibenclamide Hematoma expansion Blood-brain barrier Matrix metallopeptidase-9

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Protective effect of probiotics on intestinal barrier function in malnourished rats after liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2011年第5期10卷 489-496页

作者： Zhi-Gang Ren, Hui Liu, Jian-Wen Jiang, Li Jiang, Hui Chen, Hai-Yang Xie, Lin Zhou and Shu-Sen Zheng key laboratory of combined multi-organ Transplan- tation, Ministry of Public health, and Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China and Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China key laboratory of combined multi-organ transplantation Ministry of Public Health and Department of Hepatobiliary and Pancreatic Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China Institute of Immunology Zhejiang University School of Medicine Hangzhou 310058 China

BACKGROUND: Most patients waiting for liver transplantation have end-stage liver diseases with malnutrition, which is prone to induce intestinal barrier dysfunction after liver transplantation. We aimed to study the effect of probiotics on intestinal barrier function in malnourished rats following liver transplantation with long-term antibiotics. METHODS: Twelve Lewis rats were selected as donors. Twelve BN rats, which served as recipients, were subjected to malnutrition by semi-starvation for 4-5 weeks. They were randomly divided into two groups: a control group which received phosphate-buffered saline and a probiotics group which received Bifidobacterium and Lactobacillus. All recipients were injected with intramuscular imipenem and subcutaneous cyclosporine A. Furthermore, six normal BN rats without any drugs or operations served as a normal group. Eight days after operation, all rats were sacrificed for examination of the following parameters: serum levels of endotoxin and TNF-α, bacterial translocation, intestinal microflora, ileocecal sIgA, lymphocyte numbers, and phenotypes (CD4, CD8, αβTCR, γδTCR)ofPeyer’spatches. RESULTS: In recipients subjected to malnutrition, weight decreased by 20% and they survived until 8 days after operation. Compared with the normal group, all recipients on postoperative day 8 showed increased levels of serum endotoxin and TNF-α as well as increased counts oftranslocated bacteria. Meanwhile, there were decreases in counts of Bifidobacterium and Lactobacillus in the ileocecum, sIgA concentration, and lymphocytes of Peyer’s patches. Moreover, partial alteration in lymphocyte phenotypes was evidenced by elevated ratios of CD8 + and γδTCR + lymphocytes. In contrast, compared to the control group, supplementation with probiotics reduced the levels of serum endotoxin, TNF-α and bacterial translocation, increased the counts of Bifidobacterium and Lactobacillus, the concentration of sIgA and lymphocytes of Peyer’s patches, and also slightly

关键词： liver transplantation probiotics intestinal microflora intestinal barrier function

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Highly sensitive flexible strain sensor based on the two-dimensional semiconductor tellurium with a negative gauge factor

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Science China(Information Sciences) 2024年第7期67卷 295-304页

作者： Jiarui HE Yusong QU Shengyao CHEN Cong WANG Lena DU Xiaoshan DU Yuanyuan ZHENG Guozhong ZHAO He TIAN College of Mathematics and Physics Beijing University of Chemical Technology School of Integrated Circuits Tsinghua University Beijing China & The Beijing National Research Center for Information Science and Technology (BNRist)Tsinghua University CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology &University of Chinese Academy of Sciences Beijing key Lab of Terahertz Spectroscopy and Imaging Key Lab of Terahertz OptoelectronicsMinistry of Education Department of Physics Capital Normal University

Research on flexible strain sensors has advanced rapidly in recent years, with particular attention being devoted to two-dimensional(2D) semiconductor materials owing to their exceptional mechanical and electrical properties that are conducive to sophisticated sensing performance. However, resistive strain sensors based on 2D semiconductor materials typically exhibit positive gauge factors(GF), while materials for strain sensors with a negative GF remain elusive. We have identified a trend of reduction in the band gap of the emerging 2D semiconductor material tellurium(Te) under strain in simulations reported in past research,and have observed a negative GF in the Te-based strain sensor. In this study, we combined Te with a flexible polyethylene terephthalate(PET) substrate to manufacture a flexible strain sensor with a significantly negative GF. The results of tests revealed that the Te-based strain sensor achieved an impressive maximum sensitivity of-139.7 within a small range of bending-induced strain(< 1%). Furthermore, it exhibited excellent linearity and good cyclic stability, and was successfully applied to monitor limb movements. The work here verifies the significant potential for the use of Te-based strain sensors in next-generation flexible electronics.

关键词： 2D semiconductor materials 2D tellurium flexibleelectronics strain sensors negative gauge factor high sensitivity

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Decitabine in combination with idarubicin within a modified busulfan/cyclophosphamide conditioning regimen for patients with advanced myelodysplastic syndrome:A prospective multicenter clinical cohort study

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Chinese Medical Journal 2024年第9期137卷 1115-1117页

作者： Yigeng Cao Mingyang Wang Fuxu Wang Wenwen Guo Yueshen Ma Xiaoyun Li Yi He Aiming Pang Rongli Zhang Weihua Zhai Xin Chen Qiaoling Ma Jialin Wei Donglin Yang Yong Huang Dan Feng Jia Liu Xin Gao Shupeng Wen Wen Wang Tao Wang Ying Li Xiaosheng Fang Yingchun Li Xiaohan Zhang Yun Cai Yongqi Wang Weijie Cao Runqing Lu Sizhou Feng Rong Guo Yuewen Fu Xin Du Zhuogang Liu Xin Wang Ling Wang Liangming Ma Chuanfang Liu Xuejun Zhang Mingzhe Han Erlie Jiang Department of Hematopoietic Stem Cell transplantation Center State Key Laboratory of Experimental HematologyNational Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of HematologyBlood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300000China Department of Hematology Second Hospital of Hebei Medical UniversityHebei Key Laboratory of HematologyShijiazhuangHebei 050000China Center for Information and Resource State Key Laboratory of Experimental HematologyNational Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of HematologyBlood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300000China Department of Hematology Qilu Hospital of Shandong UniversityJinanShandong 250000China Department of Hematology Shanxi Bethune HospitalThird Hospital of Shanxi Medical UniversityTaiyuanShanxi 030032China Department of Hematology Qingdao Central HospitalUniversity of Health and Rehabilitation SciencesQingdaoShandong 266042China Department of Hematology Shandong Provincial HospitalCheeloo College of MedicineShandong UniversityJinanShandong 250000China Department of Hematology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250000China Department of Hematology Shengjing Hospital of China Medical UniversityShenyangLiaoning 110000China Department of Hematology Shenzhen Second People’s HospitalThe First Affiliated Hospital of Shenzhen UniversityShenzhen University School of MedicineShenzhenGuangdong 518000China Department of Hematology Henan Cancer HospitalCancer Hospital Affiliated Zhengzhou UniversityZhengzhouHenan 450000China Department of Hematology Department of HematologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450000China

To the Editor:Allogeneic hemopoietic stem cell transplantation(allo-HSCT)represents the only long-term survival treatment choice for patients with myelodysplastic syndromes(MDS)and MDS/myeloproliferative neoplasm(MPN).Unfortunately,post-hemopoietic stem cell transplantation(HSCT)relapse remains a cause of treatment failure and the results of salvage treatments are *** better conditioning regimens is urgently *** studies have shown synergistic antileukemic effects between decitabine(DEC)and idarubicin(IDA).[1]In an attempt to design a conditioning strategy with very low toxicity but considerable myelosuppressive activity and potential immune-enhancing effects for patients with high-risk MDS and MDS/MPN,we combined DEC and IDA with busulfan,cyclophosphamide,andudarabine for a modied myeloablative regimen in this prospective,multicenter cohort study(hereafter referred to as the“DEC/IDA study”).

关键词： regimen myelo patients

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