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Antiviral treatment of hepatitis B virus-transgenic mice by a marine organism, Styela plicata

World Journal of Gastroenterology 2006年第25期12卷 4038-4043页

作者： Rui Wang Zhen-Lan Du Wen-Jun Duan Xin Zhang Fan-Lin Zeng Xin-Xiang Wan Research Center for Pharmaceutics Southern Medical University Guangzhou 510315 Guangdong Province China hematopoietic stem cell transplantation 307 Hospital Academy of Military Medical Sciences Beijing 100039 China

AIM： To evaluate the antiviral effect of the effective ingredient of Styela plicata in a murine model of hepatitis B virus carrier. METHODS： HBV-transgenic mice were divided into 3 groups （control group, lamivudine treatment group and the effective ingredient of Styela plicata treatment group） and assigned to receive normal diet, lamivudine or the effective ingredient of Styela plicata for consecutive weeks. Serum hepatitis B surface antigen was detected by enzyme-linked immunosorbent assay （ELISA） method. Serum HBV DNA was detected by real-time polymerase chain reaction （RT-PCR）. Serum T helper （h） 1 cytokine interleukin （IL）-2 and Th2 cytokine IL-6 were detected by the quantitative sandwich enzyme immunoassay technique. Another group of HBV-transgenic mice was assigned to receive the effective ingredient of Styela plicata for consecutive weeks. The histology of liver tissue was evaluated before and after treatment. RESULTS： Twelve weeks after starting the therapy, serum hepatitis B surface antigen was significantly lowered in Styela plicata -treated mice and lamivudine-treated mice compared with the mice receiving normal diet （F12wk = 88.81, P12wk = 0.000 〈 0.01）. Serum HBV DNA was significantly lowered in Styela plicata -treated mice and lamivudine-treated mice compared with the mice receiving normal diet （F12wk = 20.71, P12wk = 0.000 〈 0.01）. However, like lamivudine, the effective ingredient of Styela plicata could not inhibit the replication of HBV completely. A rebound phenomenon of hepatitis B surface antigen and HBV DNA in sera could be found 4 wk after withdrawal of medication. Eight weeks after starting the therapy, serum levels before and after Styela plicata treatment of IL-2 were 2.41 ± 0.38 and 10.56 ± 0.78 ng/L, respectively （t8wk = -16.51, P8wk = 0.000 〈 0.01）. Compared with the serum levels of IL-2 in the normal diet-treated mice （2.48 ± 0.17 ng/L; t8wk = 13.23, P8wk = 0.000 〈 0.01）. Serum levels before and after Styela plicata treatment of IL-

关键词： Styela plicata Hepatitis B virus Transgenic mice RT-PCR Chronic hepatitis B

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

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Frontiers of Medicine 2019年第2期13卷 238-249页

作者： Xiaodong Mo Xiaohui Zhang Lanping Xu Yu Wang Chenhua Yan Huan Chen Yuhong Chen Wei Han Fengrong Wang Jingzhi Wang Kaiyan Liu Xiaojun Huang Peking University People’s Hospital Peking University Institute of HematologyBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100044China

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)(n=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

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Arsenic trioxide alleviates acute graft-versus-host disease by modulating macrophage polarization

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Science China(Life Sciences) 2020年第11期63卷 1744-1754页

作者： Xiao Liu Yan Su Xueyan Sun Haixia Fu Qiusha Huang Qi Chen Xiaodong Mo Meng Lv Yuan Kong Lanping Xu Xiaojun Huang Xiaohui Zhang Peking University People’s Hospital Beijing 100044China Peking University Institute of hematology Beijing 100044China National Clinical Research Center for Hematologic Disease Beijing 100044China Beijing Key Laboratory of hematopoietic stem cell transplantation Beijing 100044China

This study aimed to explore macrophage polarization in acute graft-versus-host disease after hematopoietic stem cell transplantation, and investigated if arsenic trioxide(ATO) could correct this imbalance. In the colon of GVHD mice, we found that the number of F4/80+iNOS+ cells as well as the expression intensity of TNF-α and IL-1β was greater in the GVHD group than in the BM group, whereas the number of F4/80+CD206+ cells and the expression intensity of IL-10 and TGF-β was greater in the BM group than in the GVHD group. We investigated the effect of ATO on GVHD mice, and found that ATO treatment clearly improved the survival of the mice and reduced the severity of GVHD. In addition, ATO reduced the number of F4/80+iNOS+ cells, and increased the number of F4/80+CD206+ cells in the colon of GVHD mice. Furthermore, ATO sharply decreased CD86 and CD80 expression, and increased CD163 and CD206 expression in macrophages induced from aGVHD patients. Therefore,ATO can modulate the M1 and M2 phenotype in GVHD mice or in macrophages from aGVHD patients. Our data suggest that macrophage polarization is involved in the pathogenesis of aGVHD, and ATO treatment modulates macrophage polarization toward an M2 phenotype.

关键词： ATO macrophage polarization acute graft-versus-host disease

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Treatment refractory mast cell leukemia with dominant gastrointestinal manifestation and concomitant skin symptoms:A case report

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World Journal of Clinical Cases 2024年第20期12卷 4317-4324页

作者： Maciej Tomasz Wysocki Maciej Gonciarz Bartosz Puła department of Gastroenterology and Internal Medicine Military Institute of Medicine-National Research InstituteWarsaw 04-141Poland department of hematology Institute of Hematology and Transfusion MedicineWarsaw 02-776Poland

BACKGROUND Mast cell leukemia(MCL),a subtype of systemic mastocytosis(SM),is an extremely rare clinical entity characterized by a very poor ***,tyrosine kinase inhibitors,and allogeneic hematopoietic cell transplantation are the only treatment options,but they cannot provide the desired outcomes in most cases of ***,other types of SM can be successfully *** disease has no specific manifestation,but gastroenterological symptoms are present in most *** SUMMARY The authors,hereby,report a case of a 46-year-old female patient diagnosed with MCL-the rarest subtype of *** patient presented to the gastroenterology clinic with multiple,various,and unspecific gastroenterological *** of skin lesions significantly contributed to a relatively prompt *** serum tryptase level was extremely high and bone the marrow aspirate showed an infiltration of atypical mast *** disease was rapidly progressive and primary refractory to chemotherapy and the patient succumbed to the illness about a month after the initiation of *** Despite its“hematological nature”,MCL,in most cases presents dominantly with unspecific gastroenterological ***,a high disease awareness among physicians other than hematologists is necessary to improve treatment *** tryptase level,due to its non-invasive nature and easy access,may serve as an initial step to estimate the probability of mastocytosis.

关键词： Mastocytosis Systemic mastocytosis Mast cell leukemia Tryptase Case report

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Chinese Medical Journal 2013年第16期126卷 3048-3052页

作者： MO Xiao-dong XU Lan-ping LIU Dai-hong CHEN Yu-hong ZHANG Xiao-hui CHEN Huan HAN Wei WANG Yu WANG Feng-rong WANG Jing-zhi LIU Kai-yan HUANG Xiao-jun Peking University People's Hospital & Institute of hematology Beijing Key laboratory of Hematopoitic Stem Cell TransplantationBeijing 100044 China

Background Chronic graft-versus-host disease （GVHD）,the commonest long-term complication after allogeneic hematopoietic stem cell transplantation （HSCT）,has a negative impact on patients＇ health related quality of life （HRQoL）.This study was designed to investigate the HRQoL in patients with chronic GVHD in *** Two hundred and sixty-four patients with chronic GVHD who were ＞24 months post-HSCT and had been in continuous complete remission since HSCT were enrolled in this retrospective *** was evaluated using an SF-36 *** analysis was used to identify the factors that affect HRQoL in patients with chronic *** HRQoL in patients categorized as having mild and moderate chronic GVHD was significantly better than in those in the severe *** the moderate chronic GVHD category,markedly poorer HRQoL was observed in patients with both multiple organ involvement and more severe organ impairment than in those without these *** to multivariate analysis,chronic GVHD severity had the greatest significant negative impact on patients＇ HRQoL; whereas being female was associated with a negative impact on psychological *** Chronic GVHD severity strongly correlates with negative impacts on patients＇ HRQoL.

关键词： chronic graft-versus-host disease health related quality of life National Institutes of Health consensus criteria

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Risk stratification system for skin and soft tissue infections after allogeneic hematopoietic stem cell transplantation:PAH risk score

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Frontiers of Medicine 2022年第6期16卷 957-968页

作者： Shan Chong Yun He Yejun Wu Peng Zhao Xiaolu Zhu Fengrong Wang Yuanyuan Zhang Xiaodong Mo Wei Han Jingzhi Wang Yu Wang Huan Chen Yuhong Chen Xiangyu Zhao Yingjun Chang Lanping Xu Kaiyan Liu Xiaojun Huang Xiaohui Zhang Peking University People’s Hospital Peking University Institute of HematologyBeijing100044China Collaborative Innovation Center of hematology Peking UniversityBeijing100044China Beijing Key Laboratory of hematopoietic stem cell transplantation Beijing100044China National Clinical Research Center for Hematologic Disease Beijing100044China

Skin and soft tissue infections(SSTIs)refer to infections involving the skin,subcutaneous tissue,fascia,and *** transplant populations with hematological malignancies,an immunocompromised status and the routine use of immunosuppressants increase the risk of SSTIs ***,to date,the profiles and clinical outcomes of SSTIs in hematopoietic stem cell transplantation(HSCT)patients remain *** study included 228 patients(3.67%)who developed SSTIs within 180 days after allogeneic HSCT from January 2004 to December 2019 in Peking University People’s *** overall annual survival rate was 71.5%.We compared the differences between survivors and non-survivors a year after transplant and found that primary platelet graft failure(PPGF),comorbidities of acute kidney injury(AKI),and hospital-acquired pneumonia(HAP)were independent risk factors for death in the study population.A PPGF-AKI-HAP risk stratification system was established with a mortality risk score of 1×PPGF+1×AKI+1×*** areas under the curves of internal and external validation were 0.833(95%CI 0.760–0.906)and 0.826(95%CI 0.715–0.937),*** calibration plot revealed the high consistency of the estimated risks,and decision curve analysis showed considerable net benefits for patients.

关键词： skin and soft tissue infections hematopoietic stem cell transplantation risk stratification system mortality

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Is t(11;14)(q13;q32) good or bad for newly diagnosed multiple myeloma?

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Chinese Medical Journal 2023年第1期136卷 96-98页

作者： Yang Liu Lu Gao Yueyun Lai Lei Wen Wenbing Duan Fengrong Wang Ling Ma Xiaojun Huang Jin Lu Peking University People’s Hospital Peking University Institute of HematologyBeijing 100044China Peking University People’s Hospital Peking University Institute of HematologyCytogenetics LaboratoryBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China Innovative Center of hematology Soochow UniversitySuzhouJiangsu 215021China.

Cytogenetic aberrations(CAs)are vital markers for risk stratification of multiple myeloma(MM).The prognostic significance of the aberration,t(11;14)(q13;q32),in MM has remained controversial over recent *** addition,studies on the heterogeneity of t(11;14)MM and the impact of additional CAs are rare.[1]We therefore conducted a retrospective study on relevant data collected at our center in order to further analyze the characteristics of Chinese patients with t(11;14)MM and elaborate on heterogeneity in their genetic profile.

关键词： t(11 q32 myeloma

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Current status and future perspective of natural killer cell therapy for cancer

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Medical Review 2023年第4期3卷 305-320页

作者： Xiangyu Zhao Minghao Lin Xiaojun Huang Peking University People's Hospital Peking University Institute of HematologyBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationNational Clinical Research Center for Hematologic DiseaseBeijingChina

Natural killer(NK)cells possess innate abilities to effectively eliminate cancer ***,because of difficulties of proliferation and easy to be induced dysfunction in the setting of cancer post NK cell therapy,the curative effect of NK cell infusion has been constrained and not been widely applicable in clinical *** rapid development of biotechnology has promoted the development of NK cell therapy for cancer *** this review,we will provide a comprehensive analysis of the current status and future prospects of NK cell therapy for cancer,focusing on the biological characteristics of NK cells,as well as strategies to enhance their targeting capabilities and overcome tumor immune suppression within the microenvironment.

关键词： natural killer cell therapy hematological malignancies solid tumors CAR-NK cell therapy

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Rapid reconstitution of NK1 cells after allogeneic transplantation is associated with a reduced incidence of graft-versus-host disease

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Science China(Life Sciences) 2018年第8期61卷 902-911页

作者： Xingxing Yu Lingling Xu Yingjun Chang Xiaojun Huang Xiangyu Zhao Peking University People's Hospital Peking University Institute of Hematology Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Beijing 100044 China Peking-Tsinghua Center for Life Sciences Beijing 100871 China Yantai Yu Huang Ding Hospital Yantai 264000 China

The balance between immunostimulation and immunoregulation in T cell immunity is achieved by maintaining specific ratios of Thl, Th2, Th3 and Trl cells. Here, we investigate levels of type 1 （IFN-gamma; NK1）, type 2 （IL-13; NK2）, type 3 （TGF-beta; NK3） and regulatory （IL-10; NKr） cytokines in peripheral blood to assess the cytokine profiles of natural killer （NK） cells following human allogeneic hematopoietic stem cell transplantation （allo-HSCT）. NK2 and NK3 cell expansion was observed after aUo-HSCT; levels of NKr ceils reached donor levels at day 15, though levels of NK1 cells were consistently lower than donor levels until day 60 after allo-HSCT. Multivariate analysis showed that a higher level of NK1 cells by day 15 was associated with a lower overall risk of acute graft-versus-host disease （GVHD）（HR 0.157, P=-0.010） as well as II-IV acute GVHD （HR 0.260, P=-0.059）. Furthermore, higher levels of NK1 cells by day 15 were correlated with lower rates of cytomegalovirus （CMV） reactivation （HR 0.040, 0.005-0.348,/9=-0.003）. These results indicate that rapid reconstitution of NK cells, especially NK1 cells, can help prevent the development of GVHD as well as CMV reactivation after allogeneic transplantation.

关键词： NK1 NK2 NK3 NKr GVHD CMV

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Modification of donor lymphocyte infusion: how to improve the outcome?

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Science China(Life Sciences) 2019年第9期62卷 1253-1256页

作者： Yu Wang Lanping Xu Chenhua Yan Xiaojun Huang Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China Peking-Tsinghua Center for Life Sciences Beijing 100871China

(HSCT),which has been acknowledged as a curative procedure,relapse of leukemia remains the leading cause of death following transplantation and is a disappointment to transplant *** relapse occurs due to leukemia cell escape from immune-mediated killing (immune escape) by pre-transplantation conditioning and post-transplantation immune *** exhaustion of donor T cells is one of the common causes of relapse,and donor lymphocyte infusions (DLIs) have the potential to reverse this immune *** who are deemed eligible for intensive treatment at this point are offered either DLI or a second *** to the contemporary understanding,DLI results in the same response and survival obtained via a second transplant but with less toxicity (Kharfan- Dabaja et al.,2018).Starting in the mid-1990s,our group along with few others demonstrated the efficacy of DLI,which was initially confirmed by the Hadassah group in Jerusalem in the late *** the first four patients (with both acute and chronic leukemias) treated by us with DLI,the initial success rate was 100%,which encouraged us to pursue this treatment further.

关键词： intensive treatment escape from along with

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