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Predictive Value of Dynamic Peri-Transplantation MRD Assessed By MFC Either Alone or in Combination with Other Variables for Outcomes of Patients with T-Cell Acute Lymphoblastic Leukemia

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Current Medical Science 2021年第3期41卷 443-453页

作者： Zhi-dong WANG Yue-wen WANG Lan-ping XU Xiao-hui ZHANG Yu WANG Huan CHEN Yu-hong CHEN Feng-rong WANG Wei HAN Yu-qian SUN Chen-hua yan Fei-fei TANG Xiao-dong MO Ya-zhe WANG yan-rong liu Kai-yan liu Xiao-jun HUANG Ying-jun CHANG Peking University People's Hospital and Peking University Institute of Hematology National Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies Chinese Academy of Medical SciencesBeijing 100005China 3Peking-Tsinghua Center for Life SciencesBeijing 100871China Peking-Tsinghua Center for Life Sciences Beijing 100871China

We performed a retrospective analysis to investigate dynamic peri-hematopoieticstem cell transplantation(HSCT)minimal/measurable residual disease(MRD)on outcomes inpatients with T-cell acute lymphoblastic leukemia(T-ALL).A total of 271 patients were enrolledand classified into three groups:unchanged ncgative MRD pre-and post-HSCT group(group A),post-MRD non-increase group(group B),and post-MRD increase group(group C).The patientsin group B and group C experienced a higher cumulative incidence of relapse(CIR)(42%vs.71%vs.16%,P<0.001)and lower leukemia-free survival(LFS)(46%vs.21%vs.70%,P<0.001)andoverall survival(OS)(50%vs.28%vs.72%,P<0.001)than in group A,but there was no significantdifference in non-relapse mortality(NRM)among three groups(14%vs.12%vs.8%,P=0.752).Multivariate analysis showed that dynamic peri-HSCT MRD was associated with CIR(HR=2.392,95%CI,1.816-3.151,P<0.001),LFS(HR=1.964,95%CI,1.546-2.496,P<0.001)and os(HR=1.731,95%CI,1.348-2.222,P<0.001).We also established a risk scoring system based ondynamic peri-HSCT MRD combined with remission status pre-HSCT and onsct of chronic graft-versus-host disease(GVHD).This risk scoring system could better distinguish ClR(c=0.730)thanthat for pre-HSCT MRD(c=0.562),post-HSCT MRD(c=0.616)and pre-and post-MRD dynamics(c=0.648).Our results confirm the outcome predictive value of dynamic peri-HSCT MRD eitheralone or in combination with other variables for patients with T-ALL.

关键词： peri-transplantation minimal residual disease risk stratification risk scoring system T-cell acute lymphoblastic leukemia

MTA2 triggered R-loop trans-regulates BDH1-mediated β-hydroxybutyrylation and potentiates propagation of hepatocellular carcinoma stem cells

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1423-1425页

作者： Heng Zhang Zhi Chang Lu-ning Qin Bin Liang Jing-xia Han Kai-liang Qiao Cheng yang yan-rong liu Hong-gang Zhou Tao Sun State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai UniversityTianjinChina Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research Tianjin International Joint Academy of BiomedicineTianjinChina Molecular Pathology Institute of Gastrointestinal Tumors Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandongChina Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Institute of Digestive DiseaseTianjinChina

Dear editor,MTA2 is associated with invasively malignant phenotypes in many types of cancers,1 but the molecular mechanism remains *** on the role of MTA2 mostly concentrated on it as a component of the NuRD complex,which functions via the NuRD complex to inhibit the transcription of downstream target genes.2 Whether MTA2 could directly exert transcriptional regulation independent of the transcription factor remains unclear and is the focus of the present study.

关键词： MTA2 hepatocellular editor

Relationship of Cell Compositions in AIIografts with Outcomes after Haploidentical Transplantation for Acquired Severe Aplastic Anemia： Effects of CD34＋ and CD14＋ Cell Doses

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Chinese Medical Journal 2018年第18期131卷 2185-2192页

作者： Le-Qing Cao Lan-Ping Xu Xiao-Hui Zhang Yu Wang yan-rong liu Kai-yan liu Xiao-Jun Huang Ying-Jun Chang Peking University Institute of Hematology Peking University People's Hospital Beijing 100044 China Peking-Tsinghua Center for Life Sciences Beijing 100871 China Collaborative Innovation Center of Hematology Peking University Beijing 100871 China

Background： The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell transplantation （SCT）. Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated haploidentical SCT （haplo-SCT） for patients with acquired severe aplastic anemia （SAA）. Methods： A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann-Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis. Results： A total of 126 patients （97.7%） achieved neutrophil engraftment, and 121 patients （95.7%） achieved platelet engraftment. At 100 days after transplantation, the cumulative incidence of II-IV acute graft-versus-host disease （GVHD） was 32.6%. After a median follow-up of 842 （range： 124-4110） days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14＋（P = 0.018） and CD34＋ cells （P 〈 0.001） were associated with a successful platelet engraftment. A successthl platelet was associated with superior survival （P 〈 0.001）. No correlation of other cell components with outcomes was observed. Conclusions： These results provide evidence and explain that higher doses ofCD34＋ and CD 14＋ cells in haploidentical allografts positively affect platelet engraftment, contributing to superior survival f

关键词： Aplastic Anemia CD14+ Monocyte CD34+ Cell Haplo-Stem Cell Transplantation Outcome

Association of Persistent Minimal Residual Disease with Poor Outcomes of Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

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Chinese Medical Journal 2018年第23期131卷 2808-2816页

作者： Jing liu Xiao-Su Zhao yan-rong liu Lan-Ping Xu Xiao-Hui Zhang Huan Chen Yu-Hong Chen Feng-rong Wang Wei Han Yu-Qian Sun Chen-Hua yan Fei-Fei Tang Xiao-Dong Mo Kai-yan liu Qiao-Zhen Fan Xiao-Jun Huang Ying-Jun Chang Peking University People's Hospital Peking University Institute of HematologyBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China Peking-Tsinghua Center for Life Sciences Beijing 100871China Collaborative Innovation Center of Hematology Peking UniversityBeijing 100871China

Background: Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo?HSCT). Methods: We retrospectively analyzed 145 consecutive AML patients undergoing allo?HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre?HSCT. Results: In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ2 = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ2 = 8.759, P = 0.003) or pre?HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ2 = 5.547, P = 0.019). In haploidentical SCT (haplo?SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre?HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo?SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo?SCT, those without persistent MRD underwent haplo?SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ2 = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200–2.382, P = 0.003), worse leukemia?free survival (HR = 1.812, 95% CI: 1.168–2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528–3.627, P < 0.001). Conclusion: Our results suggest

关键词： Allogeneic Stem Cell Transplantation Flow Cytometry Haploidentical Allograft Human Leukocyte Antigen-Matched Sibling Donor Transplantation Minimal Residual Disease

A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation

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Chinese Medical Journal 2021年第10期134卷 1199-1208页

作者： Le-Qing Cao yang Zhou yan-rong liu Lan-Ping Xu Xiao-Hui Zhang Yu Wang Huan Chen Yu-Hong Chen Feng-rong Wang Wei Han Yu-Qian Sun Chen-Hua yan Fei-Fei Tang Xiao-Dong Mo Kai-yan liu Qiao-Zhen Fan Ying-Jun Chang Xiao-Jun Huang Peking University People’s Hospital&Peking University Institute of Hematology National Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing 100871China Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies Chinese Academy of Medical Sciences2019RU029BeijingChina

Background:For patients with B cell acute lymphocytic leukemia(B-ALL)who underwent allogeneic stem cell transplantation(allo-SCT),many variables have been demonstrated to be associated with leukemia *** this study,we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after ***:A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People’s Hospital from December 2010 to December 2015 were enrolled in this retrospective *** aimed to evaluate the factors associated with transplant outcomes after allo-SCT,and establish a risk score to identify patients with different probabilities of *** univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent ***:All patients achieved neutrophil engraftment,and 95.4%of patients achieved platelet *** 5-year cumulative incidence of relapse(CIR),overall survival(OS),leukemia-free survival(LFS),and non-relapse mortality were 20.7%,70.4%,65.6%,and 13.9%,*** analysis showed that patients with positive post-transplantation minimal residual disease(MRD),transplanted beyond the first complete remission(≥CR2),and without chronic graft-versus-host disease(cGVHD)had higher CIR(P<0.001,P=0.004,and P<0.001,respectively)and worse LFS(P<0.001,P=0.017,and P<0.001,respectively),and OS(P<0.001,P=0.009,and P<0.001,respectively)than patients without MRD after transplantation,transplanted in CR1,and with cGVHD.A risk score for predicting relapse was formulated with the three above *** 5-year relapse rates were 6.3%,16.6%,55.9%,and 81.8%for patients with scores of 0,1,2,and 3(P<0.001),respectively,while the 5-year LFS and OS values decreased with increasing risk ***:This new risk score system might stratify patients with different risks of relapse,which could guide treatment.

关键词： B cell acute lymphocytic leukemia Allogeneic stem cell transplantation Minimal residual disease Disease status chronic graft-versus host disease Patient outcome

Inhibiting ceramide synthase 5 expression in microglia decreases neuroinflammation after spinal cord injury

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Neural Regeneration Research 2025年第10期20卷 2955-2968页

作者： Wei Zhang Yubao Lu Ruoqi Shen Yingjie Wu Chenrui liu Xingxing Fang Liangming Zhang Bin liu Limin rong Department of Spine Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina National Medical Products Administration(NMPA)Key Laboratory for Quality Research and Evaluation of Cell Products GuangzhouGuangdong ProvinceChina Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery GuangzhouGuangdong ProvinceChina Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery GuangzhouGuangdong ProvinceChina

Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord ***,the precise mechanism remains *** investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial *** found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high ***,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord ***,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron *** ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced ***,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling *** ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological ***2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling ***,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.

关键词： ceramide synthase 5 gasdermin D microglia neuroinflammation NLRP3 nuclear factor kappa B Pla2g7 pyroptosis sphingomyelin metabolism spinal cord injury

Low WT1 transcript levels at diagnosis predicted poor outcomes of acute myeloid leukemia patients with t(8;21) who received chemotherapy or allogeneic hematopoietic stem cell transplantation

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Chinese Journal of Cancer 2016年第7期35卷 350-358页

作者： Ya-Zhen Qin Yu Wang Hong-Hu Zhu Robert Peter Gale Mei-Jie Zhang Qian Jiang Hao Jiang Lan-Ping Xu Huan Chen Xiao-Hui Zhang yan-rong liu Yue-Yun Lai Bin Jiang Kai-yan liu Xiao-Jun Huang Peking University People's Hospital Peking University Institute of HematologyBeijing Key Laboratory of Hematopoietic Stem Cell Transplantation No.11 Xizhimen South Street Beijing P.R. China Haematology Research Center Division of Experimental MedicineDepartment of MedicineImperial College London London SW72AZUK Biostatistics Division Medical College of Wisconsin Milwaukee WI53226USA Peking-Tsinghua Center for Life Sciences Beijing 100871P.R. China

Background:Acute myeloid leukemia(AML) with t(8;21) is a heterogeneous *** AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subsequent *** study aimed to evaluate the impact of Wilm tumor gene-1(WT1) transcript levels and cellular homolog of the viral oncogene v-KIT receptor tyrosine kinase(C-KIT) mutations at diagnosis,and RUNXTRUNX1T1 transcript levels after the second consolidation chemotherapy cycle on ***:Eighty-eight AML patients with t(8;21) who received chemotherapy only or allogeneic hematopoietic stem cell transplantation(allo-HSCT) were *** who achieved remission,received two or more cycles of consolidation chemotherapy,and had a positive measureable residual disease(MRD) test result(defined as <3-log reduction in RUNX1-RUNX1T1 transcript levels compared to baseline) after 2-8 cycles of consolidation chemotherapy were recommended to receive *** who had a negative MRD test result were recommended to receive further chemotherapy up to only 8 ***1 transcript levels and C-KIT mutations at diagnosis,and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were ***:Patients who had a C-KIT mutation had significantly lower WTl transcript levels than patients who did not have a C-KIT mutation(6.7%± 10.6%vs.19.5%± 19.9%,P < 0.001).Low WTl transcript levels(<5.0%) but not C-KIT mutation at diagnosis,a positive MRD test result after the second cycle of consolidation chemotherapy,and receiving only chemotherapy were independently associated with high cumulative incidence of relapse in all patients(hazard ratio[HR]= 3.53,2.30,and 11.49;95%confidence interval[CI]1.64-7.62,1.82-7.56,and 4.43-29.82;P = 0.002,0.034,and <0.001,respectively);these conditions were also independently associated with low leukemia-free survival(HR =3.71,2.33,and 5.85;95%CI 1.82-7.56,1.17-4.64,and 2.75-12.44;P < 0.00

关键词：异基因造血干细胞移植转录水平白血病 WT1 患者化疗诊断预后

Revealing and predicting the long-term biomechanical response of orthokeratology by developing a patient-specific computational model

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 156-168页

作者： Yifeng Li Zhuoran yang Ziming yan Huibin Shi Zhanli liu Kaijie Wang Department of Engineering Mechanics School of Aerospace Engineering Tsinghua University Beijing Tongren Eye Center Beijing Tongren Hospital Capital Medical University Beijing Ophthalmology & Visual Sciences Key Lab

Orthokeratology(OK) is widely used for effective myopia correction and control. However, the incomplete understanding of its biomechanical mechanisms makes OK lens fitting rely heavily on clinician judgment, complicating accurate predictions of treatment outcomes. In this paper, we performed clinical experiments and numerical analysis to study corneal deformation modes and long-term changes in central corneal thickness. Clinical experiments were conducted on 194 Chinese myopic patients under OK treatment for 3 months. Based on the experimental data, a patient-specific computational biomechanical model for OK was established and validated. Specifically, the anisotropic mechanical properties of the cornea were incorporated into the model to describe the significant difference between its shear modulus(29.5 kPa) and tensile modulus(768.4 kPa). Additionally, a viscohyperelastic material model with a prolonged corneal relaxation time of 5.6 h was developed to capture the long-term deformation response. The results show that corneal thickness reduction in OK is primarily due to out-of-plane shear deformation,influenced by the cornea's low shear resistance. Modeling the extended corneal relaxation time is crucial for predicting long-term biomechanical responses. The computational model effectively captures long-term changes in central corneal thickness, potentially improving OK lens fitting accuracy.

关键词： orthokeratology computational biomechanical model long-term viscoelasticity myopia correction

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基于纳米红外技术的竹材细胞壁化学成分研究

光谱学与光谱分析 2017年第1期37卷 103-108页

作者：韦鹏练黄艳辉刘嵘安鑫费本华国际竹藤中心北京100102 北京林业大学北京100083

为了深入认识竹材细胞壁的精细结构,揭示竹材细胞壁的独特构造,首次应用纳米红外技术(AFM-IR)研究竹材纤维细胞壁的化学成分及其分布,探讨纳米红外技术在竹材细胞壁化学物质分布的研究方法。结果表明,利用纳米红外技术可以实现原位状态... 详细信息

为了深入认识竹材细胞壁的精细结构,揭示竹材细胞壁的独特构造,首次应用纳米红外技术(AFM-IR)研究竹材纤维细胞壁的化学成分及其分布,探讨纳米红外技术在竹材细胞壁化学物质分布的研究方法。结果表明,利用纳米红外技术可以实现原位状态下对竹材纤维细胞壁的化学组成进行分析,突破了传统红外光谱技术的衍射极限,获得纳米级的红外光谱;纳米红外技术采集的光谱与显微红外技术相比,谱峰位置基本相同,能正确反映竹材细胞壁的化学信息;纳米红外技术是竹材细胞壁化学成分纳米分布的有效研究方法。

关键词：细胞壁纳米红外显微红外拉曼光谱化学成像