33 results on '"Zhen-Yang Gu"'
Search Results
2. Akkermansia muciniphila in inflammatory bowel disease and colorectal cancer
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Zhen-Yang Gu, Wen-Long Pei, Yi Zhang, Jun Zhu, Lei Li, Zhan Zhang, and Yuanyuan Ji
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Medicine - Published
- 2021
- Full Text
- View/download PDF
3. Emerging role of long non-coding RNAs in normal and malignant hematopoiesis
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Fei-Yan Wang, Zhen-Yang Gu, Chun-Ji Gao, and Peng Lyu
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Medicine - Abstract
Abstract. Long noncoding RNAs (lncRNAs) have recently been discovered and are increasingly recognized as vital components of modern molecular biology. Accumulating evidence shows that lncRNAs have emerged as important mediators in diverse biological processes such as cell differentiation, pluripotency, and tumorigenesis, while the function of lncRNAs in the field of normal and malignant hematopoiesis remains to be further elucidated. Here, we widely reviewed recent advances and summarize the characteristics and basic mechanisms of lncRNAs and keep abreast of developments of lncRNAs within the field of normal and malignant hematopoiesis. Based on gene regulatory networks at different levels of lncRNAs participation, lncRNAs have been shown to regulate gene expression from epigenetics, transcription and post transcription. The expression of lncRNAs is highly cell-specific and critical for the development and activation of hematopoiesis. Moreover, we also summarized the role of lncRNAs involved in hematological malignancies in recent years. LncRNAs have been found to play an emerging role in normal and malignant hematopoiesis, which may provide novel ideas for the diagnosis and therapeutic targets of hematological diseases in the foreseeable future.
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- 2020
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- View/download PDF
4. Unmanipulated haploidentical peripheral blood stem cell transplantation for patients with Philadelphia-negative acute lymphoblastic leukaemia in first complete remission
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Feiyan Wang, Tong Liu, Li Wang, Nan Yang, Chengying Zhu, Meng Li, Lan Luo, Chun-Ji Gao, Zhen-Yang Gu, and Dai-Hong Liu
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Oncology ,endocrine system ,Cancer Research ,medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,Lymphoblastic Leukemia ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,Humans ,Medicine ,Retrospective Studies ,Philadelphia negative ,Peripheral Blood Stem Cell Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Complete remission ,Treatment options ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Treatment Outcome ,030220 oncology & carcinogenesis ,Lymphoblastic leukaemia ,business ,030215 immunology - Abstract
Haploidentical peripheral blood stem cell transplantation (Haplo-PBSCT) is a promising treatment option for patients with Ph-negative acute lymphoblastic leukemia (ALL). In this study, we retrospectively analyzed data from Ph-negative ALL patients who underwent haplo-PBSCT during their first complete remission (CR1), and compared the long-term outcomes between the standard-risk and high-risk patients. The 3-year probability of relapse was 7.6% and 16.7% for the standard- and high-risk group (
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- 2019
5. Haploidentical, Unmanipulated Granulocyte Colony-Stimulating Factor (G-CSF)-Primed Peripheral Blood Stem Cell Transplants for Acute Myeloid Leukemia (AML) in Remission: A Single Center Experience
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Sha-Sha Zhao, Chun-Ji Gao, Fei Li, Li-Xun Guan, Zhen-Yang Gu, Fei-Yan Wang, Nan Yang, Tao Lin, Wenrong Huang, Yu Zhou, Lan Luo, Shu Fang, Dai-Hong Liu, and Chengying Zhu
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Transplantation Conditioning ,Myeloid ,Adolescent ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Haploidy ,Single Center ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Granulocyte Colony-Stimulating Factor ,Humans ,Medicine ,Cumulative incidence ,Survival rate ,Bone Marrow Transplantation ,Original Paper ,Peripheral Blood Stem Cell Transplantation ,Transplantation ,business.industry ,Incidence ,Myeloid leukemia ,General Medicine ,Middle Aged ,medicine.disease ,Granulocyte colony-stimulating factor ,Survival Rate ,Leukemia, Myeloid, Acute ,Leukemia ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,business ,030215 immunology - Abstract
BACKGROUND Data about application of related haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) on patients with high-risk or intermediate-risk acute myeloid leukemia (AML) in the first complete remission (CR1) are lacking. In this study, we report the outcomes of using unmanipulated haploidentical allogeneic peripheral blood stem cell transplantation (haplo-PBSCT) as post-remission therapy for patients with high-risk or intermediate-risk AML in CR1. MATERIAL AND METHODS From January 2008 to July 2016, 33 patients diagnosed as high-risk or intermediate-risk AML in CR1 undergoing haplo-PBSCT in our institution were enrolled for analysis. The cumulative incidence of platelet and neutrophil recovery, the occurrence of acute graft-versus-host-disease (GVHD) and chronic GVHD, relapse and non-relapse mortality were assessed. Patients' survival rates were estimated using the Kaplan-Meier method. RESULTS The cumulative incidence of grade 2-4 acute GVHD, overall and extensive chronic GVHD was 18.2%, 9.1%, and 6.1%, respectively. 2-year probability of relapse was 9.1%. Disease-free survival and overall survival at 2 years were 72.7% and 75.8%, respectively. CONCLUSIONS Our results showed that unmanipulated haploidentical transplantation with G-CSF primed PBSC alone as a graft source could be an acceptable alternative post-remission treatment for high-risk or intermediate-risk AML patients in CR1 lacking a matched donor.
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- 2019
6. ABO Blood Type Incompatibility Is Not a Risk Factor of Outcomes for Acute Myeloid Leukemia (AML) Patients After Unmanipulated Haplo-identical Peripheral Blood Hematopoietic Stem Cell Transplantation
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Shu Fang, Nan Yang, Yi Ding, Zhe Gao, Zhen-Yang Gu, Li-Xun Guan, Lan Luo, Chengying Zhu, Zhanxiang Liu, Chun-Ji Gao, and Fei-Yan Wang
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Myeloid ,Adolescent ,medicine.medical_treatment ,Viremia ,Hematopoietic stem cell transplantation ,Haploidy ,ABO Blood-Group System ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,hemic and lymphatic diseases ,Internal medicine ,ABO blood group system ,medicine ,Humans ,Retrospective Studies ,Original Paper ,Peripheral Blood Stem Cell Transplantation ,Transplantation ,business.industry ,Donor selection ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Adult Acute Myeloid Leukemia ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Leukemia, Myeloid, Acute ,Leukemia ,Treatment Outcome ,surgical procedures, operative ,medicine.anatomical_structure ,Blood Group Incompatibility ,030220 oncology & carcinogenesis ,Female ,business ,030215 immunology - Abstract
BACKGROUND Haplo-identical hematopoietic stem cell transplantation (HSCT) has provided potential donors for patients lacking available HLA-matched donors. ABO blood type compatibility has been reported to be associated with HSCT outcomes. However, few studies have investigated the role of ABO compatibility in haplo-identical HSCT of AML patients. MATERIAL AND METHODS We retrospectively analyzed 42 adult acute myeloid leukemia (AML) patients who received unmanipulated haplo-identical peripheral blood HSCT at the Chinese PLA General Hospital between Jan 2013 and Dec 2017. We analyzed the role of ABO compatibility in engraftment, transfusion requirements, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viremia, acute graft-versus-host disease (GVHD), overall survival (OS), transplantation-related mortality (TRM), relapse, chronic GVHD, and post-transplant lymphoproliferative disorder (PTLD). RESULTS There were no significant differences between the ABO-matched group and the ABO-mismatched group in terms of engraftment, transfusion requirements, CMV and EBV viremia, OS, TRM, relapse, PTLD, and chronic GVHD. Univariate analysis revealed ABO incompatibility is not an independent risk factor of engraftment, transfusion requirements, CMV and EBV viremia, OS, TRM, relapse, PTLD, and chronic GVHD. We found a significantly higher cumulative incidence of aGVHD in the matched group compared with the mismatched group (80.95% vs. 42.86%, p=0.020). In multivariate analysis, ABO mismatch was associated with decreased risk of acute GVHD within 100 days after transplant (hazard ratio 0.492, 95% confidence interval 0.2123-1.14). However, the difference was not statistically significant (p=0.099). CONCLUSIONS This study demonstrated ABO incompatibility is not an independent risk factor of outcomes for AML patients who received unmanipulated haplo-identical peripheral blood HSCT. ABO compatibility might have limited value in haplo-identical donor selection.
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- 2019
7. Outcomes of myeloablative peripheral blood stem cell transplantation for non-complete remission patients with relapsed/refractory peripheral T cell lymphomas
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Shu-Hong Wang, Dai-Hong Liu, Zhen-Yang Gu, Wenrong Huang, Yu Zhao, Jian Bo, Fei Li, Hong-Hua Li, Lu Wang, Quan-Shun Wang, and Chun-Ji Gao
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Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,medicine.medical_treatment ,Graft vs Host Disease ,Gastroenterology ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Internal medicine ,Prevalence ,medicine ,Humans ,T-cell lymphoma ,Child ,Retrospective Studies ,Peripheral Blood Stem Cell Transplantation ,Hematology ,business.industry ,Mortality rate ,Lymphoma, T-Cell, Peripheral ,Retrospective cohort study ,Immunosuppression ,General Medicine ,Middle Aged ,Donor Lymphocytes ,medicine.disease ,Peripheral T-cell lymphoma ,Survival Rate ,030220 oncology & carcinogenesis ,Chronic Disease ,Female ,business ,Follow-Up Studies ,030215 immunology - Abstract
There was limited information about the efficacy of myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in non-complete remission (non-CR) patients with relapsed/refractory peripheral T cell lymphomas (PTCLs). We conducted a retrospective study of 21 consecutive non-CR patients with relapsed/refractory PTCLs who received myeloablative allo-PBSCT between January 2008 and June 2016. The median follow-up of survivors was 46.5 months (range, 14-105 months). The estimated 3-year relapse rate was 24% (95% CI, 9 to 43%). The 3-year non-relapsed mortality rate was 24% (95% CI, 9 to 44%). Overall, the estimated 3-year overall survival was 47% (95% CI, 25 to 66%). And the estimated 3-year progression-free survival was 46% (95% CI, 24 to 66%). Specifically, eight patients failed to achieve a CR at the first evaluation 3 months after allo-PBSCT and received withdraw of immunosuppression. Five patients also received donor lymphocytes infusions. Five (5/8, 62.5%) patients responded subsequently to these interventions (complete = 4, partial = 1). Overall, ten patients were alive at our last follow-ups, and durable CR were achieved in nine patients without further therapy. Five (50%) of these ten alive patients experienced chronic graft-versus-host disease (GVHD). Our favorable clinical outcomes suggested myeloablative allo-PBSCT was a valid therapeutic option for non-CR patients with relapsed/refractory PTCLs. The sustained CR after immunotherapeutic intervention and high prevalence of chronic GVHD in alive patients provided evidence of graft versus T cell lymphoma effects.
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- 2018
8. [Clinical Characteristics and Prognosis of U2AF1 Mutation in Patients with Acute Myeloid Leukemia]
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Ting-Yuan, Zhao, Li-Xun, Guan, Wen-Shuai, Zheng, Mei-Lu, Wang, Long-Can, Cheng, Ya-Lei, Hu, Yuan-Yuan, Xu, Zhen-Yang, Gu, and Li-Ping, Dou
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Leukemia, Myeloid, Acute ,Mutation ,Remission Induction ,Humans ,Prognosis ,Splicing Factor U2AF - Abstract
To investigate the incidence, clinical features of U2AF1 gene mutation in patients with acute myeloid leukemia(AML) and its effect of prognosis.A total of 161 patients with AML were enrolled. The second-generation sequencing method was used to detect U2AF1 gene mutation, and the relationship between U2AF1 mutation and clinical features, prognosis was analyzed.The mutation rate of U2AF1 gene in 161 AML patients was 3.73%. The counts of peripheral blood leukocytes and platelets in the U2AF1 gene mutation group were lower than those in the wild type group. The complete response rate of U2AF1 gene mutation group was 66.67%, while that in wild type group was 55.48%, which shows no significant difference between the two groups (P=0.70). The median EFS of wild type group and the mutant group was not reached and reached to 133 days, respectively (P=0.03), while the medium OS in two groups was not reached and reached to 210 days (P=0.01).The AML patients with U2AF1 mutation positive have a poor prognosis as compared with the wild type group, which may be a poor prognostic factor for acute myeloid leukemia.急性髓系白血病患者U2AF1基因突变的临床特征及预后分析.探讨U2AF1基因突变在急性髓系白血病(AML)患者中的发生率、临床特点和其对预后的影响.选取161例AML患者,应用二代测序方法检测U2AF1基因突变情况并分析其临床特征和治疗预后的关系.161例AML患者中,U2AF1基因突变率为3.73%。U2AF1基因突变组外周血白细胞数和血小板数较野生型组低。U2AF1基因突变组完全缓解率为66.67%,野生型组为55.48%,两者无统计学差异(P=0.70)。U2AF1基因野生型组和突变组的中位无事件生存期分别为未达到和133 d(P=0.03),中位总生存时间分别为未达到和210 d(P=0.01).在急性髓系白血病中,伴有U2AF1基因突变阳性患者的预后较野生型组差,这可能是急性髓系白血病预后不良的一个因素.
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- 2020
9. T Cell-Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation for Treatment of T-Lymphoblastic Lymphoma
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Zhen-Yang Gu, Dai-Hong Liu, Sha-Sha Zhao, Nan Yang, Quan-Shun Wang, Chun-Ji Gao, Xiaohong Li, Li-Xun Guan, Fei-Yan Wang, Xiaoxiong Wu, Zhe Gao, Hong-Hua Li, Wenrong Huang, Hua-Ping Wei, Lan Luo, and Chengying Zhu
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Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Myeloid ,Adolescent ,T-Lymphocytes ,medicine.medical_treatment ,CD34 ,Hematopoietic stem cell transplantation ,Haploidy ,Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,Cumulative incidence ,Young adult ,Retrospective Studies ,Original Paper ,Peripheral Blood Stem Cell Transplantation ,Transplantation ,business.industry ,Histocompatibility Testing ,Hematopoietic Stem Cell Transplantation ,Retrospective cohort study ,General Medicine ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Lymphoma ,Treatment Outcome ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,business ,030215 immunology - Abstract
BACKGROUND There is currently little information on haploidentical hematopoietic cell transplantation (haplo-HCT) for T-lymphoblastic lymphoma (T-LBL). Data about peripheral blood stem cells (PBSC) as a reliable graft source for T-LBL treatment are lacking. MATERIAL AND METHODS T-LBL patients who underwent T cell-replete haploidentical peripheral blood hematopoietic cell transplantation (haplo-PBHCT) from July 2007 to January 2017 were retrospectively evaluated. RESULTS A total of 25 patients (age ≥15 years) with median age of 24 (range 15-51) years were enrolled. The median number of CD34+ cells infused was 5.0 (1.6-14.4) 106/kg. Sustained myeloid engraftment with full donor chimerism was achieved in all patients. The cumulative incidence of grades 2 to 4 acute graft-versus-host disease (GVHD) at day 100 was 24%. Two-year extensive chronic GVHD cumulative incidence was 20%. The 3-year overall survival rate for all patients was 70%. The median survival time of the complete remission (CR) group was better than that of the non-CR group (not reached vs. 9 m) (P
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- 2018
10. G-CSF inhibits LFA-1-mediated CD4+ T cell functions by inhibiting Lck and ZAP-70
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Sha-Sha Zhao, Fei-Yan Wang, Lan Luo, Zhe Gao, Nan Yang, Zhen-Yang Gu, Li-Li Wang, Dai-Hong Liu, Yingwei Song, Li-Xun Guan, Li Wang, and Chun-Ji Gao
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medicine.medical_specialty ,ZAP-70 ,Lymphocyte ,CD3 ,T cell ,medicine.medical_treatment ,chemical and pharmacologic phenomena ,Hematopoietic stem cell transplantation ,Proinflammatory cytokine ,Internal medicine ,medicine ,Lymphocyte function-associated antigen 1 ,Hematology ,biology ,business.industry ,hemic and immune systems ,lymphocyte function-associated antigen-1 ,Molecular biology ,CD4+ T cells ,Granulocyte colony-stimulating factor ,Lck ,medicine.anatomical_structure ,Oncology ,Immunology ,biology.protein ,granulocyte colony-stimulating factor ,business ,Research Paper - Abstract
// Shasha Zhao 1, 2 , Zhenyang Gu 1 , Li Wang 1, 3 , Lixun Guan 1 , Feiyan Wang 1 , Nan Yang 1 , Lan Luo 1 , Zhe Gao 1 , Yingwei Song 4 , Lili Wang 1 , Daihong Liu 1 and Chunji Gao 1 1 Department of Hematology, Chinese PLA General Hospital, Beijing 100853, China 2 Medical School, Nankai University, Tianjin 300071, China 3 Department of Hematology and Oncology, Laoshan Branch, No. 401 Hospital of Chinese PLA, Qingdao 266101, China 4 Department of Blood Transfusion, Chinese PLA General Hospital, Beijing 100853, China Correspondence to: Chunji Gao, email: gaochunji@medmail.com.cn Keywords: granulocyte colony-stimulating factor, CD4 + T cells, lymphocyte function-associated antigen-1, Lck, ZAP-70 Received: July 26, 2016 Accepted: May 06, 2017 Published: May 25, 2017 ABSTRACT In this study, we showed that G-CSF mobilization increased the frequency of T cells, specifically CD3 + CD4 + T cells. G-CSF mobilization decreased the secretion of inflammatory cytokines of CD4 + T cells through the LFA-1/ICAM-1 signaling pathway, whereas it did not alter the TH1/TH2 ratio. We found that G-CSF mobilization inhibited LFA-1-mediated CD4 + T cell polarization and motility. In vitro , G-CSF stimulation also attenuated the polarization and adhesiveness of CD4 + T cells through the LFA-1/ICAM-1 interaction. Further investigation revealed that G-CSF mobilization suppressed LFA-1 signaling by down-regulating Lck and ZAP-70 expression in CD4 + T cells, similar results was also confirmed by in-vitro studies. These findings suggested that G-CSF directly suppressed LFA-1-mediated CD4 + T cell functions through the down-regulation of Lck and ZAP-70. The immunosuppressive effect of G-CSF mobilization deepened our understanding about peripheral blood hematopoietic stem cell transplantation. LFA-1/ICMA-1 pathway may become a potential target for graft-versus-host disease prophylaxis.
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- 2017
11. The diagnostic and prognostic value of interleukin-10 in cerebrospinal fluid for central nervous system lymphoma: a meta-analysis
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Zhe Gao, Sha-Sha Zhao, Du-Jun Zhuo, Li-Xun Guan, Bin Geng, Lan Luo, Wu-Rui Cao, Shu-Feng Liu, Fei-Yan Wang, Li Wang, Zhen-Yang Gu, De-Xun Ma, Yin Aimin, Nan Yang, Liu Chengjun, Chun-Ji Gao, Wang Songlei, Ji-Gang Chen, and Jia-Wen Xu
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Cancer Research ,medicine.medical_specialty ,Pathology ,Cochrane Library ,Sensitivity and Specificity ,Gastroenterology ,Central Nervous System Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,Internal medicine ,medicine ,Humans ,Receiver operating characteristic ,business.industry ,Hazard ratio ,Area under the curve ,Interleukin ,Hematology ,medicine.disease ,Interleukin-10 ,Lymphoma ,ROC Curve ,Oncology ,030220 oncology & carcinogenesis ,Meta-analysis ,business ,030217 neurology & neurosurgery - Abstract
Central nervous system lymphoma (CNSL) presents diagnostic and prognostic challenges. The aim of this meta-analysis was to evaluate the diagnostic and prognostic value of interleukin (IL)-10 in cerebrospinal fluid (CSF) for CNSL comprehensively. PubMed and Cochrane Library databases were searched through September 2016. Four studies with 212 CNSL patients and 262 control patients were included. The pooled sensitivity and specificity of CSF IL-10 for diagnosing CNSL were 81% (95% CI: 66-91%) and 97% (95% CI: 83-100%), respectively. The summary receiver operating characteristic (SROC) curve indicated that the area under the curve was 0.95 (0.93-0.97). The ROC curve based on extracted individual data showed that the optimal cutoff value was 6.88 pg/ml. Moreover, elevated CSF IL-10 was found to be associated with shorter progression-free survival (hazard ratio: 2.89, 95% CI: 1.13-7.41, p = .027). In conclusion, our meta-analysis showed that CSF IL-10 is an effective diagnostic and prognostic biomarker for CNSL.
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- 2017
12. Novel CD7-specific nanobody-based immunotoxins potently enhanced apoptosis of CD7-positive malignant cells
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Jialu Li, Jinle Tang, Pengjun Jiang, Zhen-Yang Gu, Xuejun Zhu, Zhishu Gong, Yuan Yu, Juhua Yu, Huimin Meng, Dan Chen, Huyong Zheng, Xingding Zhang, Lin Yang, Gangli An, Lei Yuan, and Lin Qi
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0301 basic medicine ,VHH ,Antineoplastic Agents ,Apoptosis ,Antigens, CD7 ,Mice, SCID ,Jurkat cells ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Mice, Inbred NOD ,Immunotoxin ,Cell Line, Tumor ,hemic and lymphatic diseases ,Tumor Cells, Cultured ,Animals ,Humans ,Leukemia-Lymphoma, Adult T-Cell ,Medicine ,Cytotoxic T cell ,Pseudomonas exotoxin ,business.industry ,Immunotoxins ,leukemia ,Myeloid leukemia ,Single-Domain Antibodies ,medicine.disease ,Xenograft Model Antitumor Assays ,In vitro ,immunotoxin ,3. Good health ,nanobody ,Leukemia ,030104 developmental biology ,target delivery drug ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,business ,Research Paper - Abstract
Various CD7-targeting immunotoxins have been tested for its potential in treating CD7+ malignant patients but none of those immunotoxins was approved clinically because of lacking enough efficacy and safety. Here we successfully constructed the monovalent and bivalent CD7 nanobody-based immunotoxins PG001 and PG002, both conjugated with a truncated derivative of Pseudomonas exotoxin A respectively. The prokaryotic system expressed immunotoxins not only maintained their binding specificity for CD7-positive cells with a Kd of 16.74 nM and 3.6 nM for PG001 and PG002 respectively, but also efficiently promoted antigen-restricted apoptosis of the CD7-positive leukemia cell lines Jurkat and CEM, and primary T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) cells with an in vitro cytotoxic activity (EC50) in the range of 23-30 pM for PG002. In NOD/SCID mice transplanted with CEM cells, PG001 and PG002 prevented engraftment of the cells and markedly prolonged mouse survival. Owing to the efficient antigen-restricted anti-leukemic activity of PG002, this CD7 nanobody-based immunotoxin exhibited a superior anti-CD7 positive malignancies activity than previously reported immunotoxins, and may represent a promising therapeutic strategy in treating CD7-positive leukemia and lymphoma, which still remain a significant clinical challenge.
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- 2016
13. Single- Versus Double-Unit Umbilical Cord Blood Transplantation for Hematologic Diseases: A Systematic Review
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Fei-Yan Wang, Cheng-Ying Zhu, Zhen-Yang Gu, Rui Gao, Hua-Ping Wei, De-Xun Ma, Chao Zhang, Shu-Feng Liu, Li Wang, Li-Xun Guan, Chun-Ji Gao, and Liu Chengjun
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Blood Platelets ,Risk ,medicine.medical_specialty ,Transplantation Conditioning ,Platelet Engraftment ,Neutrophils ,Clinical Biochemistry ,CD34 ,Graft vs Host Disease ,Disease ,030204 cardiovascular system & hematology ,Cochrane Library ,Disease-Free Survival ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Recurrence ,Internal medicine ,Medicine ,Humans ,Bone Marrow Transplantation ,business.industry ,Umbilical Cord Blood Transplantation ,Incidence (epidemiology) ,Biochemistry (medical) ,Hematology ,Hematologic Diseases ,Double-Unit Umbilical Cord Blood Transplantation ,Hematologic Neoplasms ,Cord Blood Stem Cell Transplantation ,Neoplasm Recurrence, Local ,business ,030215 immunology - Abstract
Controversial results exist regarding the clinical benefits of single- vs double-unit umbilical cord blood transplantation (UCBT) in patients with hematologic diseases. A systematic review was conducted to evaluate this issue. The PubMed, Embase, and Cochrane Library databases were searched up to May 2018. A total of 25 studies including 6571 recipients were identified. Although double-unit UCB contained higher doses of total nucleated cells and CD34+ cells, it offered no advantages over single-unit UCB in terms of hematologic recovery, including the rate and speed of neutrophil and platelet engraftment. Double-unit UCBT was associated with higher incidences of grades II-IV acute and extensive chronic graft-vs-host disease, accompanied by a lower relapse incidence, which may be attributed to a graft-vs-graft effect induced by double-unit UCB. However, transplant-related mortality, disease-free survival, and overall survival were comparable between single- and double-unit UCBT. Although double-unit UCBT confers no clinical advantages over single-unit UCBT, certain patients, such as those at high risk of relapse, might benefit from double-unit UCBT, a possibility that needs to be clarified in future randomized trials.
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- 2018
14. [Application of Chimeric Antigen Receptor-Modified NK Cells in Multiple Myeloma]
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Hua-Ping, Wei, Nan, Yang, Zhen-Yang, Gu, Sha-Sha, Zhao, Fei-Yan, Wang, Lan, Luo, Li-Xun, Guan, and Chun-Ji, Gao
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Killer Cells, Natural ,Receptors, Antigen ,Cell Line, Tumor ,Lentivirus ,Receptors, Antigen, T-Cell ,Humans ,Multiple Myeloma - Abstract
To explore the killing effect of CAR (CD138-CD28-CD3ζ)-NK cells on myeloma cells through construction of CAR(CD138-CD28-CD3)-NK cells.The antiCD138scFv-CD28-CD3 zeta plasmid pcDNA3.1 was constructed, which then together with 3 plasmid lentiviral packaging system were transfected into 293T cells, the virus was collected. Furthermore, in order to get the stably transfected cell line, the NK92MI cell line was infected by the virus, then the positive cells were screened by puromycin. The expression of the CARNK cells were verified by RT-PCR and Western blot. At last the ability of secreting cytokine CD107a was detected by flow cytometry, and the statistical analysis was carried out to verify the anti-myeloma effect of CAR-NK cells.Gene fragment of the CAR(antiCD138scFv-CD28-CD3ζ) was constructed successfully by gene engineering technique in vitro, and the gene sequence was verified to be correct by sequencing. By virus packaging technology, the virus expressing the protein of the CAR was obtained. PCR and Western blot verified the expression of CAR fusion protein on the sufurce of NK cells. The cell killing experiment confirmed that the CAR-NK cells possessed the ability to secrete cytokine CD107a superior to control cells and showed the obvious killing effect on multiple myeloma cells.The CAR can be constructed in vitro, and express on NK92 cells. The CAR-NK cells can kill the multiple myeloma cells expressing CD138 antigen, thereby plays an antimyeloma effect.
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- 2018
15. [Clinical Characteristics, Treatment and Prognosis of PTLD after allogeneic Hematopoietic Stem Cell Transplantation]
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Zhan-Xiang, Liu, Wen-Rong, Huang, Meng, Li, Zhen-Yang, Gu, Cheng-Ying, Zhu, Ning, Lu, Sheng, Yao, Shu-Hong, Wang, Fei, Li, Xiao-Ning, Gao, Dai-Hong, Liu, and Chun-Ji, Gao
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Epstein-Barr Virus Infections ,Hematopoietic Stem Cell Transplantation ,Humans ,Prognosis ,Lymphoproliferative Disorders ,Retrospective Studies - Abstract
To study the clinical characteristics of patients with post-transplantation lymphoproliferative disease (PTLD) after allogeneic peripheral blood hematopoietic stem cell transplantation, and to improve the understanding and diagnosis of PTLD.The clinical data of 244 patients underwent allogeneic hematopoietic stem cell transplantation in the General Hospital of PLA from May 2014 to April 2017 were analyzed retrospectively. The follow-up time was up to November 30, 2017. The incidence, risk factors, treatment and survival of patients with PTLD were statistically analyzed.Among the 244 cases the PTLD occurred in 22 cases, the incidence rate was 9.02%, 5 of them were diagnosed by pathology, and 17 were diagnosed clinically. All of them had EB virus infection. They were all ATG user, either underwent related haploidentical hematopoietic stem cell transplantation or unrelated hematopoietic stem cell transplantation, 20 cases were treated with rituximab or rituximab combined with γ-globulin, glucocorticoid, ERV+CTL, chemotherapy and 17 showed the effective response, with a total effective rate of 85%. The median follow-up time was 122 days, the median survival time was 5 months (1-22 months) and the total survival rate was 50%.The incidence of PTLD after allogeneic peripheral blood hematopoietic stem cell transplantation closely relates with EB virus infection. The application of ATG in the preconditioning scheme is a high risk factor for the onset of PTLD. In the case of no pathological diagnosis, clinical and laboratory examinations should be actively combined so as to define clinical diagnosis. The riturimab should be used more and more for patients with PTLD.
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- 2018
16. Efficacy and safety of mesenchymal stromal cells for the prophylaxis of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials
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Li-Xun Guan, Shu-Feng Liu, Chun-Ji Gao, Du-Jun Zhuo, Fei-Yan Wang, Cheng-Ying Zhu, Zhen-Yang Gu, Zhe Gao, Li Wang, Liu Chengjun, De-Xun Ma, Ji-Gang Chen, Rui Gao, Chang-Chun Xu, and Shu Fang
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Graft vs Host Disease ,Bone Marrow Cells ,Hematopoietic stem cell transplantation ,Infections ,Mesenchymal Stem Cell Transplantation ,law.invention ,03 medical and health sciences ,Randomized controlled trial ,law ,Recurrence ,Internal medicine ,medicine ,Humans ,Randomized Controlled Trials as Topic ,Hematology ,business.industry ,Incidence (epidemiology) ,Incidence ,Mesenchymal stem cell ,Hematopoietic Stem Cell Transplantation ,Mesenchymal Stem Cells ,General Medicine ,medicine.disease ,Allografts ,Fetal Blood ,030104 developmental biology ,Graft-versus-host disease ,Treatment Outcome ,Organ Specificity ,Meta-analysis ,Relative risk ,business - Abstract
A meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the efficacy and safety of mesenchymal stromal cells (MSCs) for the prophylaxis of chronic graft-versus-host disease (cGVHD) in patients with hematological malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Six studies involving 365 patients were included. The pooled results showed that MSCs significantly reduced the incidence of cGVHD (risk ratio [RR] 0.63, 95% confidence interval [CI] 0.46 to 0.86, P = 0.004). Favorable prophylactic effects of MSCs on cGVHD were observed with umbilical cord-derived, high-dose, and late-infusion MSCs, while bone marrow-derived, low-dose, and coinfused MSCs did not confer beneficial prophylactic effects. In addition, MSC infusion did not increase the risk of primary disease relapse and infection (RR 1.02, 95% CI 0.70 to 1.50, P = 0.913; RR 0.89, 95% CI 0.44 to 1.81, P = 0.752; respectively). Moreover, there was an apparent trend toward increased overall survival (OS) in the MSC group compared with that in the control group (RR 1.13, 95% CI 0.98 to 1.29, P = 0.084). In conclusion, this meta-analysis demonstrated that MSC infusion is an effective and safe prophylactic strategy for cGVHD in patients with hematological malignancies undergoing allo-HSCT.
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- 2018
17. The efficacy and safety of sirolimus-based graft-versus-host disease prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials
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Hua-Ping Wei, Zhen-Yang Gu, Li-Li Wang, Dai-Hong Liu, Lan Luo, Li Wang, Sha-Sha Zhao, Dandan Li, Rui-Ren Zhai, Quan-Shun Wang, Chun-Ji Gao, Zhao-Xia Pang, and Xiao-Li Zhao
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Incidence (epidemiology) ,Immunology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Confidence interval ,Surgery ,law.invention ,Regimen ,Graft-versus-host disease ,Randomized controlled trial ,law ,Relative risk ,Internal medicine ,medicine ,Immunology and Allergy ,business ,Survival rate - Abstract
BACKGROUND The efficacy and safety of sirolimus (SIR)-based graft-versus-host disease (GVHD) prophylaxis in patients who were subjected to allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain to be clarified; this meta-analysis was conducted to evaluate these factors. STUDY DESIGN AND METHODS Data from original research were obtained from PubMed, Embase, and Cochrane central register of controlled trials databases. Randomized controlled trials (RCTs) evaluating the efficacy of SIR-based prophylaxis in allo-HSCT were included. The risk ratio (RR), with a 95% confidence interval (CI), was used to pool data. The random effects model was used, irrespective of the presence or absence of heterogeneity. RESULTS Five RCTs were included in the meta-analysis. SIR was observed to significantly decrease the incidence of Grade II to IV acute GVHD (aGVHD; RR, 0.65; 95% CI, 0.47-0.89). However, the incidence of Grade III to IV aGVHD and chronic GVHD was not decreased (RR, 0.91; 95% CI, 0.59-1.40; RR, 1.04; 95% CI, 0.88-1.23, respectively). An analysis of the toxic effects of SIR revealed that SIR effected a significant increase in the incidence of sinusoidal obstructive syndrome (RR, 2.24; 95% CI, 1.26-4.01), while that of thrombotic microangiopathy was not significantly increased (RR, 2.48; 95% CI, 0.87-7.06). Moreover, SIR did not improve event-free survival and overall survival (RR, 0.97; 95% CI, 0.85-1.10; and RR, 0.92; 95% CI, 0.82-1.02, respectively). CONCLUSION This meta-analysis indicated that the SIR-based regimen is an effective and safe alternative prophylaxis strategy for GVHD.
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- 2015
18. [Abnormal Notch-Hes Signaling Pathways and Acute Leukemia -Review]
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Zhen-Yang, Gu, Li, Wang, and Chun-Ji, Gao
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DNA-Binding Proteins ,Homeodomain Proteins ,Leukemia ,Receptors, Notch ,Basic Helix-Loop-Helix Transcription Factors ,Humans ,Transcription Factor HES-1 ,Carrier Proteins ,Signal Transduction - Abstract
The abnormal activation of Notch signaling is closely related to the development of acute leukemia (AL). The core elements of the Notch signaling system include Notch receptors, Notch ligands, CSL DNA-binding proteins, and effectors like target genes. Any factors, which affect ligands, receptors, signal transducers and effectors, can influence the signal transduction of Notch signaling greatly. Based on the role of Notch signaling in AL, several targeted drugs against Notch upstream signaling have been developed. However, due to the complexity and pleiotropic effects of Notch upstream signaling, these targeted drugs display strong side effects. Thus, Hes (Hairy Enhancer of Split) factors as a primary Notch effector, also play an important role in the pathogenesis of AL. This review summarizes recent progresses on Notch-Hes signaling in AL, hopping to provide references for further excavation of the Notch-Hes signaling, and lay foundations for developing the next generation of targeted drugs.
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- 2017
19. Risk Factors for Acute Graft-Versus-Host Disease After Allogeneic Haematopoietic Stem Cell Transplantation: A Single-Center Experience
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Sha-Sha Zhao, Bo Cai, Zhen-Yang Gu, Fei-Yan Wang, Dai-Hong Liu, Xiaoyu Wang, Li Wang, Lan Luo, Chun-Ji Gao, Li-Xun Guan, Li-Li Wang, and Hua-Ping Wei
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0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Single Center ,Risk Assessment ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,immune system diseases ,Risk Factors ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,Humans ,Cumulative incidence ,Aged ,Retrospective Studies ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Retrospective cohort study ,General Medicine ,Odds ratio ,Middle Aged ,Tissue Donors ,surgical procedures, operative ,030104 developmental biology ,030220 oncology & carcinogenesis ,Acute Disease ,Female ,business ,Complication ,Risk assessment - Abstract
BACKGROUND Acute graft-versus-host disease (aGVHD) remains the most common and challenging complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). An important obstacle to the therapeutic effect of aGVHD is the inability to identify risk factors for an individual patient at the onset of symptoms. We performed a retrospective study with the aim of defining clinically meaningful pre-transplantation risk factors for grades II-IV aGVHD patients. MATERIAL AND METHODS To identify pre-transplantation risk factors for grades II-IV aGVHD after allo-HSCT, we performed a retrospective study in 292 patients who underwent allo-HSCT at our center from January 2010 to July 2015. RESULTS The cumulative incidence of grades II-IV aGVHD was 36.6±2.8%. The most common target organ of aGVHD was the skin (46.7%), followed by the gastrointestinal tract (29.9%). The risk factors we identified included HLA-mismatched related donors (odds ratio [OR], 3.21; 95% confidence interval [CI], 1.82-5.67) and conditioning regimens containing TBI but no ATG (OR, 2.66; 95% CI, 1.40-5.06). Simultaneously, transplantation with an identical sibling donor (OR, 0.31; 95% CI, 0.18-0.55) and the use of ATG in the conditioning regimen containing TBI (OR 0.37; 95% CI, 0.15-0.93) were two factors found to be associated with a decreased risk of grades II-IV aGVHD. CONCLUSIONS Our study suggests that pre-transplantation characteristics of donor and recipient play an important role in identifying patients at high risk for grades II-IV aGVHD, which provide a direction for the prevention and treatment of aGVHD in the future.
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- 2017
20. Similar outcomes after haploidentical transplantation with post-transplant cyclophosphamide versus HLA-matched transplantation: a meta-analysis of case-control studies
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Sha-Sha Zhao, Li Wang, Li-Xun Guan, Zhen-Yang Gu, Lei Yuan, Fei-Yan Wang, Lan Luo, Meng Li, Qingyi Wang, Chun-Ji Gao, Nan Yang, Zhe Gao, Dai-Hong Liu, Jon C. Aster, and Wenrong Huang
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medicine.medical_specialty ,endocrine system ,HLA-matched ,post-transplant cyclophosphamide ,Cochrane Library ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Progression-free survival ,hematopoietic cell transplantation ,Hematology ,business.industry ,haploidentical ,Case-control study ,similar outcomes ,Chinese people ,Surgery ,Transplantation ,surgical procedures, operative ,Oncology ,030220 oncology & carcinogenesis ,Meta-analysis ,Relative risk ,business ,030215 immunology ,Research Paper - Abstract
// Zhenyang Gu 1, 2, * , Li Wang 1, 3, * , Lei Yuan 1, * , Wenrong Huang 1 , Meng Li 1 , Lixun Guan 1 , Qingyi Wang 4 , Zhe Gao 1 , Shasha Zhao 1 , Lan Luo 1 , Feiyan Wang 1 , Nan Yang 1 , Daihong Liu 1 , Jon C. Aster 2 and Chunji Gao 1 1 Department of Hematology, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China 2 Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA 3 Department of Hematology and Oncology, Laoshan Branch, No. 401 Hospital of Chinese PLA, Qingdao, China 4 Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA * These authors have contributed equally to this work Correspondence to: Chunji Gao, email: gaochunji@medmail.com.cn Jon C. Aster, email: jaster@rics.bwh.harvard.edu Keywords: post-transplant cyclophosphamide, haploidentical, hematopoietic cell transplantation, HLA-matched, similar outcomes Received: January 17, 2017 Accepted: June 02, 2017 Published: June 29, 2017 ABSTRACT Background: Outcomes of haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplant cyclophosphamide (PT-Cy) have greatly improved. It remains unknown whether haplo-HCT with PT-Cy was associated with poor outcomes when compared with HLA-matched HCT. To address this issue, we performed a meta-analysis to compare outcomes of haplo-HCT with PT-Cy with those of HLA-matched HCT. Methods: A systematic search for case-control studies were performed in PubMed, Embase and Cochrane Library databases. Using a random model, the risk ratios (RRs) and 95% confidence intervals (95% CI) were pooled for the final analysis. Results: Nine case-control studies including 2258 patients (827 patients in the haplo-HCT with PT-Cy group, 748 controls from HLA-matched related donors (MRD), and 683 controls from HLA-matched unrelated donors (MUD)) met the inclusion criteria. No differences were found between haplo-HCT with PT-Cy and HLA-matched HCT with regard to acute graft-versus-host-disease (GVHD), non-relapse mortality, relapse, progression free survival and overall survival. However, haplo-HCT with PT-Cy was found to be associated with a lower incidence of moderate to severe chronic GVHD (Haplo vs MRD: RR=0.54; 95% CI=0.39-0.75; Haplo vs MUD: RR=0.70; 95% CI=0.56-0.88). Conclusions: The results of this meta-analysis suggest that haplo-HCT with PT-Cy can achieve comparable outcomes with those of HLA-matched HCT. Haploidentical donors can be a feasible and valid alternative when conventional HLA-matched donors are unavailable.
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- 2017
21. Efficacy and safety of thrombopoietin receptor agonists in patients with primary immune thrombocytopenia: A systematic review and meta-analysis
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Fei-Yan Wang, Nan Yang, Li-Xun Guan, Hua-Ping Wei, Lan Luo, Hai-Yan Zhang, Zhen-Yang Gu, Xiao-Ping Chen, Chun-Ji Gao, Zhe Gao, Sha-Sha Zhao, and Li Wang
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Blood Platelets ,medicine.medical_specialty ,Thrombopoietin Receptor Agonists ,030204 cardiovascular system & hematology ,Gastroenterology ,Article ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Humans ,Medicine ,Platelet ,Adverse effect ,Randomized Controlled Trials as Topic ,Autoimmune disease ,Purpura, Thrombocytopenic, Idiopathic ,Multidisciplinary ,business.industry ,medicine.disease ,Confidence interval ,030220 oncology & carcinogenesis ,Relative risk ,Meta-analysis ,Immunology ,business ,Receptors, Thrombopoietin - Abstract
Immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased platelet destruction and impaired platelet production. In this study, we conducted a systematic review and meta-analysis to determine the efficacy and safety of thrombopoietin receptor agonists (TPO-RAs) in primary ITP patients. Thirteen randomized controlled trials were included in this study, the pooled results of which demonstrated that TPO-RAs significantly increased platelet response (R) and durable response (DR) rates [risk ratio (RR): 2.77, 95% confidence interval (CI): 2.01–3.82, P = 5.9 × 10−10; RR: 7.52, 95% CI: 3.94–14.35, P = 9.2 × 10−10; respectively] and that TPO-RAs significantly reduced the incidences of any or severe bleeding events (RR: 0.80, 95% CI: 0.67–0.95, P = 0.013; RR: 0.52, 95% CI: 0.27–0.99, P = 0.048; respectively). Moreover, our results indicated that there was a significant reduction in the proportion of patients needing rescue medications in the TPO-RA groups compared with the control groups (RR: 0.50, 95% CI: 0.42–0.59, P = 2.0 × 10−15) and that the rates of any or severe adverse events were similar between the TPO-RA and control regimens (RR: 1.01, 95% CI: 0.92–1.10; RR: 0.74, 95% CI: 0.54–1.01; respectively). These findings demonstrate that TPO-RAs are an effective and safe second-line treatment option for primary ITP patients.
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- 2016
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22. [Effect of rhG-CSF Mobilization on S1P5 Expression in T Lymphocyte Subsets of Allo-HSCT Donors]
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Meng, Li, Li-Xun, Guan, Zhen-Yang, Gu, Sha-Sha, Zhao, Fei-Yan, Wang, Hua-Ping, Wei, Li, Wang, Hong-Hua, Li, Jian, Bo, and Chun-Ji, Gao
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Receptors, Lysosphingolipid ,T-Lymphocyte Subsets ,Granulocyte Colony-Stimulating Factor ,Hematopoietic Stem Cell Transplantation ,Humans ,Transplantation, Homologous ,Flow Cytometry ,Recombinant Proteins - Abstract
To explore the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) mobilization on S1P5 expression in T lymphocyte subsets of allo-HSCT donors.The peripheral blood was collected from 10 allo-hematopoietic stem cell transplantation (allo-HSCT) donors before and after mobilization with rhG-CSF for 4 days. The flow cytometry was used to detect S1P5 expression in T lymphocyte subsets.There was no S1P5 expression on the surface of T-lymphocytes both before and after rhG-CSF mobilization. After fixation with permeabilization agent, S1P5 expression could be detected in lymphocytes after rhG-CSF mobilization, which indicates S1P5 may be located in cells. Compared with level before rhG-CSF mobilization, S1P5 expression was significantly increased in T lymphocyte subsets after rhG-CSF mobilization, CD3(+)T cells (57.92±2.32)% vs (7.94±1.47)%(P0.05), CD4(+)T cells (72.58±1.73)% vs (5.48±0.82)%(P0.05), CD8(+)T cells(51.79±3.57)% vs (6.46±1.01)%(P0.05),CD3-/CD56(+)NK cells(40.00±1.47)% vs(4.97±0.74)%(P0.05). The up-regulated level of S1P5 expression in CD4(+)T cells was most high(P0.05).S1P5 expression significantly increases in T lymphocyte subsets after rhG-CSF mobilization, and the up-regulated level of S1P5 expression in CD4(+)T cells is the most high.
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- 2016
23. [Application of CRISPR/Cas9 Gene Editing Technique to Establish S1PR5 Gene Knockout Mice]
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Zhen-Yang, Gu, Xiao-Li, Zhao, Nan, Yang, Li, Wang, Fei-Yan, Wang, Li-Li, Wang, and Chun-Ji, Gao
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Gene Editing ,Mice, Inbred C57BL ,Mice, Knockout ,Gene Knockout Techniques ,Mice ,Receptors, Lysosphingolipid ,Microinjections ,Zygote ,Mutation ,Animals ,CRISPR-Cas Systems ,Plasmids ,RNA, Guide, Kinetoplastida - Abstract
To establish the S1PR5 gene knockout mouse model by using CRISPR/Cas9 gene editing technique so as to provide the tool for studying the regulating role of sphingosine-1-phosphate receptor 5 (S1PR5) in allogeneic hematopoietic stem cell transplantation.Single guide RNA (sgRNA) plasmids against the exon 3 of S1PR5 were designed and constructed. Then the sgRNA and hCas9 were transcribed by T7 RNA polymerase in vitro. Cas9 mRNA and sgRNA were mixed and microinjected into fertilized eggs of C57BL/6 mice. T7E1 digestion and gene sequencing were used to detect the mutations of S1PR5. Quantitative PCR (qPCR) and Western blot were used to detect the expression of S1PR5.Finally 2 kinds of F2 generation of homozygous S1PR5 deficent mice (S1PR5-170/-170 mice and S1PR5-215/-215 mice) were gained, and in these 2 model mice the S1PR5 did not express at mRNA and protein levels.A mouse model with S1PR5 dificiency has been successfully established, which shall lay a foundation for future investigation of S1PR5.
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- 2016
24. [Expression Profile of lncRNA NONHSAT040475 in Peripheral Blood Leukocytes of Healthy Persons]
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Fei-Yan, Wang, Lan, Luo, Sha-Sha, Zhao, Hua-Ping, Wei, Li, Wang, Zhen-Yang, Gu, Li-Xun, Guan, Nan, Yang, Zhe, Gao, Li-Li, Wang, and Chun-Ji, Gao
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Killer Cells, Natural ,Leukocyte Count ,Leukocytes ,Humans ,RNA, Long Noncoding ,Flow Cytometry - Abstract
To investigate the expression profile of lncRNA NONHSAT040475 in peripheral blood leukocytes of healthy persons.The peripheral blood mononuclear cells were collected from 10 healthy volunteers, the CD3(+) T cells,CD19(+) B cells,CD56(+) NK cells and granulocytes were purified and sorted by flow cytometry. Then, the expression of lncRNA NONHSAT040475 in peripheral blood leukocyte subsets was detected by real-time quantitative PCR.the expression levels of lncRNA NONHSAT040475 were various in lymphocyte subsets, its expression in B lymphocytes was significantly higher, as compared with T lymphocytes, while the expressions of lncRNA NONHSAT040475 in NK cells and granulocytes were relative low(P0.01).lncRNA NONHSAT040475 is widely expressed in human peripheral blood leukocytes, and mainly expressed in B lymphocytes, therefore, laying the foundation for further study of B lymphocyte-related diseases. This study has brought a new opportunity for diagnosing and illustrating the molecular mechanism of hematologic disorder or autoimmune disease.
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- 2016
25. [P53-mediated Regulatory Mechanism of Ran Transcription in Multiple Myeloma Cells]
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Lei, Yuan, Zhen-Yang, Gu, and Chun-Ji, Gao
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ran GTP-Binding Protein ,Cell Line, Tumor ,Imidazoles ,Humans ,Tumor Suppressor Protein p53 ,Multiple Myeloma ,Piperazines - Abstract
To investigate the role of p53 on ran transcription in myeloma cells.Using real-time fluorescence quantitative PCR, the ran transcription level was measured in 8 human myeloma cell lines such as OPM-2, RPMI-8226, U-266, KAS6/1, ANML-6, H-929, MM1.S and MOLP-8. The ran transcription level and P53 expression were detected by Q-PCR in MM1.S treated with Nutlin-3a for 24, 48 and 72 hours, respectively. The Western blot was used to detect the expression levels of ran and P53 proteins, and ran expression level after transfection of MM1.S cells using different concentration of plasmids which express the P53 luciferase reporter.H-929 and MM1.S cells showed the highest ran transcription level among the above-mentioned 8 cell lines (P0.05). After treatment with Nutlin-3a, ran transcription level in MM1.S cells decreased (P0.05), (r=-1.00, P=0.04) and P53 expression increased (r=1.00, P=0.06) in time-dependence manner. The detection by p53 luciferase reporter showed that the ran transcription decreased and the plasmid increased to 25 ng (P0.05).This study demonstrated that ran is a target gene regulated by P53 in myeloma cells for the first time.
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- 2016
26. [Therapeutic Efficacy Analysis of Allogeneic Peripheral Blood Hematopoietic Stem Cell Transplantation for 14 Adult Patients with T Lymphoblastic Lymphoma]
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Hua-Ping, Wei, Xiao-Li, Zhao, Wen-Rong, Huang, Jian, Bo, Hong-Hua, Li, Yu, Zhao, Hai-Yan, Zhu, Yu, Jin, Lei, Yuan, Li, Wang, Zhen-Yang, Gu, Nan, Yang, Fei-Yan, Wang, Quan-Shun, Wang, Dai-Hong, Liu, Li, Yu, and Chun-Ji, Gao
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Adult ,Survival Rate ,Peripheral Blood Stem Cell Transplantation ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Humans ,Neoplasm Recurrence, Local ,Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ,Disease-Free Survival ,Retrospective Studies - Abstract
To investigate the therapeutic efficacy of allogeneic peripheral blood hematopoietic stem cell transpdantation (allo-HSCT) for T lymphoblastic lymphoma (T-LBL).The clinical data of 14 adult patients with T-LBL treated with allo-HSCT were collected, the hematopoietic reconstruction, survival and relapse, as well as overall survival (OS) rate, event-free survival (EFS) rate of 1, 3 and 5 years were analysed retrospectively.All the patients were engrafted with neutrophil successfully, the median time of absolute neutrophil count0.5 × 10(9)/L was 13 (10-19) d; 13 patients were engrafted with platelets successfully, the median time of Plt count20 × 10(9)/L was 17 (12-62) days. The acute GVHD occurred in 6 patients, but among them only 1 case with 3 grade of aGVHD; out of 14 patients, 5 developed chronic GVHD. The transplant-related mortality at 100 days was 7.1% (1/14), mainly from coronary heart disease and pulmonary infection. The median follow-up time was 26.5 months, the estimated 1, 3 and 5 year OS rate was 85.7%, 47.6% and 38.1%, respectively, and estimated 1, 3 year EFS rate was 85.7%, 34.4% and 34.1%, respectively. The relapse rate was 42.8% (6/14) and the median relapse time was 22.5% months after transplantation. Up to now, 7 patients still survive, 1 patient out of them have survived for 103 months.The allo-HSCT is a safe and effective method for treatment of T-LBL.
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- 2016
27. Mesenchymal stem cells provide prophylaxis against acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: A meta-analysis of animal models
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Yonghui Li, Nan Yang, Sha-Sha Zhao, Chun-Ji Gao, Li-Xun Guan, Hua-Ping Wei, Li-Li Wang, Hai-Yan Zhang, Li Wang, Lan Luo, Zhen-Yang Gu, Dai-Hong Liu, Zhe Gao, and Fei-Yan Wang
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Mesenchymal Stem Cell Transplantation ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Internal medicine ,medicine ,graft-versus-host disease ,Animals ,Humans ,Transplantation, Homologous ,Animal testing ,animal experimentation ,mesenchymal stem cells ,Hematology ,business.industry ,Mesenchymal stem cell ,Hematopoietic Stem Cell Transplantation ,medicine.disease ,Chinese people ,Rats ,Clinical trial ,meta-analysis ,030104 developmental biology ,Graft-versus-host disease ,030220 oncology & carcinogenesis ,Relative risk ,Immunology ,Models, Animal ,business ,Research Paper - Abstract
// Li Wang 1, 2, * , Haiyan Zhang 3, * , Lixun Guan 1 , Shasha Zhao 1 , Zhenyang Gu 1 , Huaping Wei 1 , Zhe Gao 1 , Feiyan Wang 1 , Nan Yang 1 , Lan Luo 1 , Yonghui Li 1 , Lili Wang 1 , Daihong Liu 1 , Chunji Gao 1 1 Department of Hematology, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China 2 Department of Hematology and Oncology, Laoshan Branch, No. 401 Hospital of Chinese PLA, Qingdao, China 3 Department of Hematology, Linyi People’s Hospital, Linyi, China * These authors have contributed equally to this work Correspondence to: Chunji Gao, email: gaochunji@medmail.com.cn Keywords: mesenchymal stem cells, graft-versus-host disease, hematopoietic stem cell transplantation, meta-analysis, animal experimentation Received: April 30, 2016 Accepted: July 28, 2016 Published: August 12, 2016 ABSTRACT A meta-analysis of animal models was conducted to evaluate the prophylactic effects of mesenchymal stem cells (MSCs) on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation. A total of 50 studies involving 1848 animals were included. The pooled results showed that MSCs significantly reduced aGVHD-associated mortality (risk ratio = 0.70, 95% confidence interval 0.62 to 0.79, P = 2.73×10 -9 ) and clinical scores (standardized mean difference = -3.60, 95% confidence interval -4.43 to -2.76, P = 3.61×10 -17 ). In addition, MSCs conferred robust favorable prophylactic effects on aGVHD across recipient species, MSC doses, and administration times, but not MSC sources. Our meta-analysis showed that MSCs significantly prevented mortality and alleviated the clinical manifestations of aGVHD in animal models. These data support further clinical trials aimed at evaluating the efficacy of using MSCs to prevent aGVHD.
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- 2016
28. [Role of Mesenchymal Stem Cells in Preventing GVHD: A Meta-Analysis]
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Li, Wang, Zhen-Yang, Gu, Xiao-Li, Zhao, Hua-Ping, Wei, Lan, Luo, Sha-Sha, Zhao, Dai-Hong, Liu, Quan-Shun, Wang, and Chun-Ji, Gao
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China ,Recurrence ,Incidence ,Chronic Disease ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Humans ,Mesenchymal Stem Cells ,Randomized Controlled Trials as Topic - Abstract
To evaluate the efficacy of mesenchymal stem cells (MSC) in the prevention of graft versus host disease (GVHD) after hematopoietic stem cell transplantation (HSCT).Randomized controlled trials (RCT) were identified from PubMed (1950.1-2014.3), EMbase (1970.1-2014.3), Cochrane Central Register of Controlled Trials (CENTRAL, issue 4, 2014) of the Cochrane Library, China Biological Medicine (CBM, 1978.1-2014.3). References of retrieved articles were also identified. The quality of each RCT was evaluated by the Cochrane collaboration's tool for assessing the risk of bias. Data analysis was performed with Review Manager 5.1 to evaluate the efficacy of MSC in the prevention of GVHD after HSCT.A total of 3 English articles involving 117 patients were included. Meta-analysis indicated that MSC did not reduce the incidence of acute GVHD and chronic GVHD (RR:0.44, 95% CI: 0.08 to 2.51, P = 0.35; RR:0.85, 95% CI: 0.54 to 1.33, P = 0.47). However, MSC did not increase occurrence of relapse and cytomegalovirus infection (RR:1.52, 95% CI:0.63 to 3.68, P = 0.35;RR:1.05, 95% CI:0.72 to 1.53, P = 0.78). Finally, MSC did not improve overall survival rate of patients received HSCT (RR:1.06, 95% CI:0.79 to 1.43, P = 0.71).MSC may have a preventive effect on GVHD in patients undergoing HSCT. However, the evidence is weak due to the small sample sizes. Thus, a reliable conclusion about the preventive effect of MSC on GVHD at the moment has not been made, further larger, high quality, randomized and controlled trials are warranted.
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- 2015
29. Efficacy of oral cryotherapy on oral mucositis prevention in patients with hematological malignancies undergoing hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials
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Dandan Li, Rui-Ren Zhai, Li-Li Wang, Zhao-Xia Pang, Chun-Ji Gao, Xiao-Li Zhao, Sha-Sha Zhao, Hua-Ping Wei, Quan-Shun Wang, Zhen-Yang Gu, Li Wang, Dai-Hong Liu, and Lan Luo
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Male ,medicine.medical_specialty ,PubMed ,medicine.medical_treatment ,lcsh:Medicine ,Cryotherapy ,Hematopoietic stem cell transplantation ,Cochrane Library ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Mucositis ,Humans ,lcsh:Science ,Randomized Controlled Trials as Topic ,Stomatitis ,Multidisciplinary ,business.industry ,Incidence (epidemiology) ,lcsh:R ,Hematopoietic Stem Cell Transplantation ,medicine.disease ,Surgery ,Parenteral nutrition ,Meta-analysis ,Hematologic Neoplasms ,Female ,lcsh:Q ,business ,Research Article - Abstract
Objectives Controversy exists regarding whether oral cryotherapy can prevent oral mucositis (OM) in patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT). The aim of the present meta-analysis was to evaluate the efficacy of oral cryotherapy for OM prevention in patients with hematological malignancies undergoing HSCT. Methods PubMed and the Cochrane Library were searched through October 2014. Randomized controlled trials (RCTs) comparing the effect of oral cryotherapy with no treatment or with other interventions for OM in patients undergoing HSCT were included. The primary outcomes were the incidence, severity, and duration of OM. The secondary outcomes included length of analgesic use, total parenteral nutrition (TPN) use, and length of hospital stay. Results Seven RCTs involving eight articles analyzing 458 patients were included. Oral cryotherapy significantly decreased the incidence of severe OM (RR = 0.52, 95% CI = 0.27 to 0.99) and OM severity (SMD = -2.07, 95% CI = -3.90 to -0.25). In addition, the duration of TPN use and the length of hospitalization were markedly reduced (SMD = -0.56, 95% CI = -0.92 to -0.19; SMD = -0.44, 95% CI = -0.76 to -0.13; respectively). However, the pooled results were uncertain for the duration of OM and analgesic use (SMD = -0.13, 95% CI = -0.41 to 0.15; SMD = -1.15, 95% CI = -2.57 to 0.27; respectively). Conclusions Oral cryotherapy is a readily applicable and cost-effective prophylaxis for OM in patients undergoing HSCT.
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- 2015
30. [Effects of rhG-CSF Stimulation in vitro on the Adhesion and Polarization of Human CD4⁺T Lymphocytes]
- Author
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Sha-Sha, Zhao, Zhen-Yang, Gu, Meng, Li, Xiao-Li, Zhao, Lan, Luo, Li-Xun, Guan, Li-Li, Wang, and Chun-Ji, Gao
- Subjects
CD4-Positive T-Lymphocytes ,Cell Polarity ,In Vitro Techniques ,Middle Aged ,Intercellular Adhesion Molecule-1 ,Lymphocyte Activation ,Chemokine CXCL12 ,Lymphocyte Function-Associated Antigen-1 ,Recombinant Proteins ,Cell Movement ,Granulocyte Colony-Stimulating Factor ,Cell Adhesion ,Leukocytes, Mononuclear ,Humans ,Aged - Abstract
The adhesion and polarization of T lymphocytes involved in the adhesive interaction of lymphocyte function-associated antigen 1 (LFA-1) with its ligand intercellular adhesion molecule 1 (ICAM-1). This study was aimed to investigate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) stimulation in vitro on the adhesion and polarization of CD4⁺ T cells of healthy human in peripheral blood. The peripheral blood mononuclear cells were collected from 12 healthy volunteers. The CD4⁺ T cells were sorted by miniMACS. The sorted CD4⁺ T cells were incubated with rhG-CSF for 24 h, then the adhesion and polarization of CD4⁺ T cells activated by stroma cell-derived factor -1α (SDF-1α) and ICAM-1 were detected by ELISA and inverted microscope. The results showed that the percentage of adhesion CD4⁺T cells in the experimental group (rhG-CSF acting on the healthy adult volunteers) (61.9 ± 5.9)% was lower than that in the control group (healthy adult volunteers without rhG-CSF stimulation) (68.3 ± 7.3)% (P0.05). The percentage of polarized CD4⁺T cells in the experimental group (24.3 ± 4.3)% was also lower than that in control group (47.1 ± 5.1)% (P0.05). It is concluded that the adhesion and polarization of CD4⁺T lymphocytes can be inhibited after rhG-CSF stimulation.
- Published
- 2014
31. [Effects of rhG-CSF mobilization on the polarization and migration of donor's CD4(+)T lymphocytes]
- Author
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Zhen-Yang, Gu, Meng, Li, Sha-Sha, Zhao, Bo, Cai, Xiao-Li, Zhao, Li-Xun, Guan, Li-Li, Wang, and Chun-Ji, Gao
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Male ,Young Adult ,Adolescent ,Cell Movement ,Case-Control Studies ,Granulocyte Colony-Stimulating Factor ,Humans ,Female ,Middle Aged ,Recombinant Proteins ,Tissue Donors - Abstract
The polarization and migration of T lymphocytes involves the adhesive interaction of lymphocyte function-associated antigen 1(LFA-1) with its ligand intercellular adhesion molecule 1 (ICAM-1). This study was aimed to investigate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) mobilization on the polarization and migration of donor's CD4(+) T cells in peripheral blood. The peripheral blood mononuclear cells were collected from 10 healthy volunteers and 10 donors on the fifth day of mobilization with rhG-CSF. And the CD4(+)T cells were purified by miniMACS. The polarization and migration of CD4(+) T cells activated by stroma cell-derived factor -1α (SDF-1α) and ICAM-1 were detected by using inverted and confocal microscopes respectively. The results showed that the percentage of polarized CD4(+)T cells from donors(32.42 ± 4.91)% was lower than that from healthy controls(56.55 ± 5.35)% (P0.01), the migration velocity of CD4(+)T cells from donors (7.06 ± 1.44 µm/min) was also lower than that of healthy controls(9.05 ± 1.91 µm/min)(P0.01). It is concluded that the polarization and migration of CD4(+)T lymphocytes is impaired after rhG-CSF mobilization.
- Published
- 2014
32. Rabies Cases in the West of China Have Two Distinct Origins.
- Author
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Xiao-Yan Tao, Zhen-Yang Guo, Hao Li, Wen-Tao Jiao, Xin-Xin Shen, Wu-Yang Zhu, Simon Rayner, and Qing Tang
- Subjects
Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
In China, rabies remains an ongoing threat to public health. Although control efforts have been effective in reducing the number of annual cases, the virus continues to spread into new areas. Tibet, Qinghai, Gansu and Ningxia in western China have, until recently, reported only a handful of events. However, since 2011, there have been increasing numbers of cases recorded in these areas. In this study, we report the collection and analysis of samples collected from these regions. We find that cases originate from two different sources. Strains collected from Gansu and Ningxia are closely related to the primary lineage associated with the current epizootic, whereas those from Tibet and Qinghai are related to the Arctic-like-2 lineage that is most commonly associated with wildlife cases in China. Thus, it appears that while the epizootic is beginning to encroach into Gansu and Ningxia, Tibet and Qinghai a significant number of rabies cases originate from wildlife.
- Published
- 2015
- Full Text
- View/download PDF
33. Molecular phylodynamic analysis indicates lineage displacement occurred in Chinese rabies epidemics between 1949 to 2010.
- Author
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Xiao-Yan Tao, Qing Tang, Simon Rayner, Zhen-Yang Guo, Hao Li, Shu-Lin Lang, Cui-Ping Yin, Na Han, Wei Fang, James Adams, Miao Song, and Guo-Dong Liang
- Subjects
Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Rabies remains a serious problem in China with three epidemics since 1949 and the country in the midst of the third epidemic. Significantly, the control of each outbreak has been followed by a rapid reemergence of the disease. In 2005, the government implemented a rabies national surveillance program that included the collection and screening of almost 8,000 samples. In this work, we analyzed a Chinese dataset comprising 320 glycoprotein sequences covering 23 provinces and eight species, spanning the second and third epidemics. Specifically, we investigated whether the three epidemics are associated with a single reemerging lineage or a different lineage was responsible for each epidemic. Consistent with previous results, phylogenetic analysis identified six lineages, China I to VI. Analysis of the geographical composition of these lineages revealed they are consistent with human case data and reflect the gradual emergence of China I in the third epidemic. Initially, China I was restricted to south China and China II was dominant. However, as the epidemic began to spread into new areas, China I began to emerge, whereas China II remained confined to south China. By the latter part of the surveillance period, almost all isolates were China I and contributions from the remaining lineages were minimal. The prevalence of China II in the early stages of the third epidemic and its established presence in wildlife suggests that it too replaced a previously dominant lineage during the second epidemic. This lineage replacement may be a consequence of control programs that were dominated by dog culling efforts as the primary control method in the first two epidemics. This had the effect of reducing dominant strains to levels comparable with other localized background stains. Our results indicate the importance of effective control strategies for long term control of the disease.
- Published
- 2013
- Full Text
- View/download PDF
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