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| 1 | An analytical biomarker for treatment of patients with recurrent B-ALL after remission induced by infusion of anti-CD19 chimeric antigen receptor T(CAR-T) cells显示文摘Anti-CD19 chimeric antigen receptor-modified T(CAR-T-19) cells have emerged as a powerful targeted immunotherapy for B-cell lineage acute lymphoblastic leukemia with a remarkable clinical response in recent trials. Nonetheless, few data are available on the subsequent clinical monitoring and treatment of the patients, especially those with disease recurrence after CAR-T-19 cell infusion. Here, we analyzed three patients who survived after our phase I clinical trial and who were studied by means of biomarkers reflecting persistence of CAR-T-19 cells in vivo and predictive factors directing further treatment. One patient achieved 9-week sustained complete remission and subsequently received an allogeneic hematopoietic stem cell transplant. Another patient who showed relapse after 20 weeks without detectable leukemia in the cerebrospinal fluid after CAR-T-19 cell treatment was able to achieve a morphological remission under the influence of stand-alone low-dose chemotherapeutic agents. The third patient gradually developed extensive extramedullary involvement in tissues with scarce immune-cell infiltration during a long period of hematopoietic remission after CAR-T-19 cell therapy. Long-term and discontinuous increases in serum cytokines(mainly interleukin 6 and C-reactive protein) were identified in two patients(Nos. 1 and 6) even though only a low copy number of CAR molecules could be detected in their peripheral blood. This finding was suggestive of persistent functional activity of CAR-T-19 cells. Combined analyses of laboratory biomarkers with their clinical manifestations before and after salvage treatment showed that the persistent immunosurveillance mediated by CAR-T-19 cells would inevitably potentiate the leukemia-killing effectiveness of subsequent chemotherapy in patients who showed relapse after CAR-T-19-induced remission. | Yajing Zhang Wenying Zhang Hanren Dai Yao Wang Fengxia Shi Chunmeng Wang Yelei Guo Yang Liu Meixia Chen Kaichao Feng Yan Zhang Chuanjie Liu Qingming Yang Suxia Li Weidong Han | 2016 | Science China(Life Sciences)2016，59，4： | 6 |
| 2 | 2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma显示文摘Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS. | Ping Li Yang Liu Yun Liang Jian Bo Sujun Gao Yongxian Hu Yu Hu He Huang Xiaojun Huang Hongmei Jing Xiaoyan Ke Jianyong Li Yuhua Li Qifa Liu Peihua Lu Heng Mei Ting Niu Yongping Song Yuqin Song Liping Su Sanfang Tu Jianxiang Wang Depei Wu Zhao Wang Kailin Xu Zhitao Ying Qingming Yang Yajing Zhang Fengxia Shi Bin Zhang Huilai Zhang Xi Zhang Mingfeng Zhao Weili Zhao Xiangyu Zhao Liang Huang Jun Zhu Wenbin Qian Weidong Han Aibin Liang | 2023 | Cancer Biology & Medicine2023，20，2： | 3 |
| 3 | Analysis of adverse events following the treatment of autologous cytokine-induced killer cells for adoptive immunotherapy in malignant tumour sufferers显示文摘 | Yajing Zhang Lei Xia Yan Zhang Yao Wang Xuechun Lu Fengxia Shi Yang Liu Meixia Chen Kaixhao Feng Wenying Zhang Xiaobing Fu Weidong Han | 2015 | Expert Opinion on Biological Therapy2015，，： | 1 |
| 4 | Diagnostic and therapeutic advancements for aerobic vaginitis显示文摘 | Cha Han Wenjuan Wu Aiping Fan Yingmei Wang Huiying Zhang Zanjun Chu Chen Wang Fengxia Xue | 2015 | Archives of Gynecology and Obstetrics2015，，2： | 1 |
| 5 | Impaired immunomodulatory ability of bone marrow mesenchymal stem cells on CD4 + T cells in aplastic anemia显示文摘 | Jianping Li Shihong Lu Shaoguang Yang Wen Xing Jianming Feng Wenqian Li Qinjun Zhao Hao Wu Meili Ge Fengxia Ma Hui Zhao Bin Liu Lei Zhang Yizhou Zheng Zhong Chao Han | 2012 | Results in Immunology2012，，： | 1 |
| 6 | Comparative Proteomic Analysis of Rice Shoots Exposed to High Arsenate显示文摘Consumption of arsenic contaminated water and cereals is a serious threat to humans all over the world.Rice(Oryza sativa'Nipponbare'),as a main cereal crop,can accumulate arsenic more than 10 fold that of in other cereals.To gain a comprehensive understanding of the response of rice subjected to 100 mM arsenate stress,a comparative proteomic analysis of rice shoots in combination with morphological and biochemical investigations have been performed in this study.The results demonstrated that arsenate suppressed the growth of rice seedlings,destroyed the cellular ultra structure and changed the homeostasis of reactive oxygen species.Moreover,a total of 38 differentially displayed proteins,which were mainly involved in metabolism,redox and protein metabolism,were identi ed.The data suggest the arsenic can inhibit rice growth through negatively affecting chloroplast structure and photosynthesis.In addition,upregulation of the proteins involved in redox and protein metabolism might help the rice to be resistant or tolerant to arsenic toxicity.In general,this study improves our understanding about the rice arsenic responsive mechanism. | Yanli Liu Ming Li Chao Han Fengxia Wu Bingkun Tu Pingfang Yang | 2013 | Journal of Integrative Plant Biology2013，55，10： | 0 |
| 7 | Expression and purification of recombinant human hemangiopoietin in Escherichia coli显示文摘Objective:To express the soluble recombinant hemangiopoietin protein in E.coli BL21(DE3).Methods:Using human fetal live cDNA as a template,a partial cDNA fragment of HAPO coding N-terminal region was subcloned into plasmids pTrc99,pQE60 and pET32c to construct different recombinant prokaryotic expression systems.After selecting,the soluble rhHAPO fusion protein was expressed stably in E.coli BL21(DE3) by vector pET32c-HAPO and further isolated by nickelnitrilotriacetic acid(NTA) affinity chromatography.After cleavage with enterokinase,the rhHAPO protein was applied to Fast Flow SP sepharose column.Results:The rhHAPO protein had a purity of more than 95% and a good bioactivity based on the cell adhesion assay in ECV304 cells.Conclusion:We have established a protein engineering system to produce rhHAPO which may provide the possibility for clinical application. | Ren Qian Ma Fengxia Chen Zhong Lu Shihong Han Zhibo Liu Yongjun Xu Bin Zhang Xiangyu Han Zhongchao | 2008 | Journal of Medical Colleges of PLA(China)2008，23，3： | 0 |
| 8 | Identification of cross-reactive CD8^(+)T cell receptors with high functional avidity to a SARS-CoV-2 immunodominant epitope and its natural mutant variants显示文摘Despite the growing knowledge of T cell responses in COVID-19 patients,there is a lack of detailed characterizations for T cell-antigen interactions and T cell functions.Here,with a predicted peptide library from SARS-CoV-2 S and N proteins,we found that specific CD8+T cell responses were identified in over 75%of COVID-19 convalescent patients(15/20)and an epitope from the N protein,N361-369(KTFPPTEPK),was the most dominant epitope from our selected peptide library.Importantly,we discovered 2 N361-369-specific T cell receptors(TCRs)with high functional avidity that were independent of the CD8 co-receptor.These TCRs exhibited complementary cross-reactivity to several presently reported N361-369 mutant variants,as to the wild-type epitope.Further,the natural functions of these TCRs in the cytotoxic immunity against SARS-CoV-2 were determined with dendritic cells(DCs)and the lung organoid model.We found that the N361-369 epitope could be normally processed and endogenously presented by these different types of antigen presenting cells,to elicit successful activation and effective cytotoxicity of CD8+T cells ex vivo.Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2,and illuminated potential ways of viral clearance in COVID-19 patients.These results indicate that utilizing CD8-independent TCRs against SARS-CoV-2-associated antigens may provide functional superiority that is beneficial for the adoptive cell immunotherapies based on natural or genetically engineered T cells.Additionally,this information is highly relevant for the development of the next-generation vaccines with protections against continuously emerged SARS-CoV-2 mutant strains. | Chao Hu Meiying Shen Xiaojian Han Qian Chen Luo Li Siyin Chen Jing Zhang Fengxia Gao Wang Wang Yingming Wang Tingting Li Shenglong Li Jingjing Huang Jianwei Wang Ju Zhu Dan Chen Qingchen Wu Kun Tao Da Pang Aishun Jin | 2022 | Genes & Diseases2022，9，1： | 0 |
| 9 | Differences in Phosphorus Absorption and Utilization Efficiency of Soybean in Mature Period under Phosphorus Stress显示文摘In this study,four phosphorus-inefficient soybean genotypes( D03,D05,D17 and D18) and four phosphorus-efficient soybean genotypes( D31,D34,D37 and D38) were selected as experimental materials for soil culture experiment under high and low phosphorus treatments,to investigate the grain yield,phosphorus content,phosphorus uptake and the relationship between phosphorus utilization efficiency and phosphorus efficiency of soybean genotypes with different phosphorus efficiency in mature period. According to the experimental results,under low phosphorus treatment,four phosphorus-efficient soybean genotypes exhibited significantly high phosphorus uptake in mature period,especially for D31 and D37; however,three phosphorus-efficient genotypes showed no advantages in adaptability of phosphorus utilization efficiency,while only D31 exhibited high phosphorus utilization and absorption capacity. Correlation analysis and path analysis showed that phosphorus deficiency of soybean was mainly determined by phosphorus absorption capacity,and phosphorus deficiency under(- P) treatment was significantly higher than( + P) treatment. Phosphorus uptake and phosphorus utilization efficiency posed great direct effects on phosphorus efficiency,and phosphorus uptake exhibited a greater contribution; in addition,these two factors both posed small indirect effects. In mature period at reproductive growth stage,phosphorus absorption efficiency( phosphorus uptake) was the main variation source of phosphorus efficiency of various soybean genotypes in mature period. Therefore,strong phosphorus uptake and accumulation capacity of phosphorus-efficient soybean genotypes in mature period is an important nutrition foundation for the information of high grain yield. | Yanli ZHANG Hongling QI Fengxia LU Ming HAN Panpan WANG | 2014 | Agricultural Biotechnology2014，3，6： | 0 |
| 10 | 诱导性多能干细胞的低基因组稳定性使非同源末端连接增加显示文摘背景与目的诱导性多能干细胞(induced pluripotent stem cells,iPSCs)和胚胎干细胞(embryonic stem cells,ESCs)具有许多共同特征,包括相似的形态、基因表达和体外分化谱。然而,iPSCs的基因组稳定性远低于ESCs。在本研究中,我们研究了iPSCs中DNA损伤修复的改变是否为其具有更大诱变倾向的原因。方法将小鼠iPSCs、ESCs和胚胎成纤维细胞暴露于电离辐射(4 Gy),导致双链DNA断裂。照射4 h后使用全基因组重测序评估DNA损伤修复的保真度。我们还分析了分别源自iPSCs或ESCs的小鼠的基因组稳定性。结果照射后,与胚胎干细胞和胚胎成纤维细胞相比,iPSCs具有较低的DNA损伤修复能力,有更多的体细胞突变和短片段插入缺失。iPSCs有更多的非同源末端连接DNA修复和更少的同源重组DNA修复。源自iPSCs的小鼠比ESCs小鼠以及C57对照小鼠的DNA损伤修复能力更低。结论本研究结果部分表明,iPSCs的低基因组稳定性及其在体内的高致瘤性是由DNA损伤修复的低保真度所致。 | Minjie Zhang Liu Wang Ke An Jun Cai Guochao Li Caiyun Yang Huixian Liu Fengxia Du Xiao Han Zilong Zhang Zitong Zhao Duanqing Pei Yuan Long Xin Xie Qi Zhou Yingli Sun | 2019 | 癌症2019，38，8： | 0 |
| 11 | Analysis of anticancer compound,indole-3-carbinol,in broccoli using a new ultrasound-assisted dispersive-filter extraction method based on poly(deep eutectic solvent)-graphene oxide nanocomposite显示文摘Indole-3-carbinol(I3C),an important anticancer compound found in broccoli,has attracted considerable attention.The rapid extraction and accurate analysis of I3C in the pharmaceutical industry in broccoli is challenging as I3C is unstable at low pH and high temperature.In this study,a rapid,accurate,and lowcost ultrasound-assisted dispersive-filter extraction(UADFE)technique based on poly(deep eutectic solvent)-graphene oxide(PDES-GO)adsorbent was developed for the isolation and analysis of I3C in broccoli for the first time.PDES-GO with multiple adsorption interactions and a fast mass transfer rate was synthesized to accelerate adsorption and desorption.UADFE was developed by combining dispersive solid-phase extraction(DSPE)and filter solid-phase extraction(FSPE)to realize rapid extraction and separation.Based on the above two strategies,the proposed PDES-GO-UADFE method coupled with high-performance liquid chromatography(HPLC)allowed the rapid(15-16 min),accurate(84.3%-96.4%),and low-cost(adsorbent:3.00 mg)analysis of I3C in broccoli and was superior to solid-phase extraction,DSPE,and FSPE methods.The proposed method showed remarkable linearity(r=0.9998;range:0.0840-48.0 mg/g),low limit of quantification(0.0840 mg/g),and high precision(relative standard deviation<5.6%).Therefore,the PDES-GO-UADFE-HPLC method shows significant potential in the field of pharmaceutical analysis for the separation and analysis of anti-cancer compounds in complex plant samples. | Yanan Yuan Huanhuan Chen Yehong Han Fengxia Qiao Hongyuan Yan | 2022 | Journal of Pharmaceutical Analysis2022，12，2： | 0 |
| 12 | Deep pedigree analysis reveals family specific ‘‘fingerprint” pattern of DNA methylation for men显示文摘DNA methylation plays an essential role in mammalian development[1].However,how DNA methylation is inherited between generations and if there is family-specific DNA methylation pattern remains to be elucidated[2].In this study,we collect male blood samples including a big pedigree of the descendants of an ancient Chinese empire and samples from different haplogroups to study their whole genome DNA methylation pattern.We find 115 male family-specific methylation sites from three families.The difference of whole genome DNA methylation pattern correlates | Guochao Li Minjie Zhang Hua Chen Ke An Zongzhi Liu Fengxia Du Caiyun Yang Xiao Han Li Jin Hui Li Yan Zhang Jie Qiao Yingli Sun | 2018 | Science Bulletin2018，63，1： | 0 |
| 13 | Lower genomic stability of induced pluripotent stem cells reflects increased non-homologous end joining显示文摘Background:Induced pluripotent stem cells(iPSCs)and embryonic stem cells(ESCs)share many common features,including similar morphology,gene expression and in vitro differentiation profiles.However,genomic stability is much lower in iPSCs than in ESCs.In the current study,we examined whether changes in DNA damage repair in iPSCs are responsible for their greater tendency towards mutagenesis.Methods:Mouse iPSCs,ESCs and embryonic fibroblasts were exposed to ionizing radiation(4 Gy)to introduce dou-ble-strand DNA breaks.At 4 h later,fidelity of DNA damage repair was assessed using whole-genome re-sequencing.We also analyzed genomic stability in mice derived from iPSCs versus ESCs.Results:In comparison to ESCs and embryonic fibroblasts,iPSCs had lower DNA damage repair capacity,more somatic mutations and short indels after irradiation.iPSCs showed greater non-homologous end joining DNA repair and less homologous recombination DNA repair.Mice derived from iPSCs had lower DNA damage repair capacity than ESC-derived mice as well as C57 control mice.Conclusions:The relatively low genomic stability of iPSCs and their high rate of tumorigenesis in vivo appear to be due,at least in part,to low fidelity of DNA damage repair. | Minjie Zhang Liu Wang Ke An Jun Cai Guochao Li Caiyun Yang Huixian Liu Fengxia Du Xiao Han Zilong Zhang Zitong Zhao Duanqing Pei Yuan Long Xin Xie Qi Zhou Yingli Sun | 2018 | Cancer Communications2018，38，1： | 0 |
| 14 | Incidence of Major Adverse Cardiovascular and Cerebrovascular Events in Chinese Patients Undergoing Percutaneous Coronary Intervention with Iodixanol: An Observational Postauthorization Study显示文摘Objective:This study aimed to evaluate the major adverse cardiovascular and cerebrovascular events(MACCEs)and overall safety profile associated with iodixanol in Chinese patients undergoing percutaneous coronary intervention(PCI).Methods:Patients at 30 centers in China registered in the OpenClinic v3.6 database from October 30,2013,to October 7,2015,were included in the study.The primary endpoint was in-hospital MACCEs including target lesion revascularization(TLR),stroke,stent thrombosis,cardiac death,and PCI-related myocardial infarction(MI)within 72 h post-PCI.Secondary endpoints were MACCEs from 72 h to 30 d post-PCI and other safety events within 30 d post-PCI.Results:A total of 3,042 patients were enrolled.The incidence of MACCEs within 72 h post-PCI was 2.33%(n=71),including cardiac death(0.03%,n=1)and PCI-related MI(2.30%,n=70).The incidence of MACCEs from 72 h to 30 d post-PCI was 0.16%(n=5),including cardiac death(0.10%,n=3),PCI-related MI(0.03%,n=1),and TLR for stent thrombosis(0.03%,n=1).The incidence of composite angiographic or procedural complications was 2.86%(n=87);233(7.86%)patients had results suggesting contrast-induced acute kidney injury.Conclusions:These findings indicate that the use of iodixanol in Chinese patients undergoing PCI is associated with a low incidence of MACCEs,confirming its safety in this population. | Xiaozeng Wang Dengfeng Ma Tianchang Li Bao Li Xi Su Yanqing Wu Zhimin Du Zheng Ji Ping Yang Baisong Yang Xuebin Cao Junxia Li Fengxia Hou Ziping Cheng Banglong Xu Yaling Han | 2023 | Cardiology Discovery2023，3，2： | 0 |
| 15 | Assessment of Marginal Emissions Factor in Power Systems Under Ramp-Rate Constraints显示文摘Reducing carbon emissions in the power sector is critical for transitioning to a sustainable and low-carbon future.Estimating carbon efficiency of demand side response(DSR)in the power system is an important step towards realizing potential environmental benefits.Marginal emission factor(MEF)is an effective tool for estimating incremental changes in carbon emissions as a result of a change in demand.However,estimation methods currently used for evaluating MEF can be improved upon,specifically,by factoring in the ramp-rate constraint of generators in the fuel cost based merit order dispatch.In this paper is described a new method for MEF assessment under ramp-rate constraints;the method is then compared with two conventional estimations in a British power system.Three fuel price scenarios are used to conduct a sensitivity analysis of MEFs to fuel prices.Conclusions are drawn that can pave the way for future improvements in estimating MEF in power systems. | Zhanghua Zheng Fengxia Han Furong Li Jiahui Zhu | 2015 | CSEE Journal of Power and Energy Systems2015，1，4： | 0 |
| 16 | Safety Risk Assessment of Overturning Construction of Towering Structure Based on Cloud Matter–Element Coupled Model显示文摘Rapid urbanization has led to a surge in the number of towering structures,and overturning is widely used because it can better accommodate the construction of shaped structures such as variable sections.The complexity of the construction process makes the construction risk have certain randomness,so this paper proposes a cloudbased coupled matter-element model to address the ambiguity and randomness in the safety risk assessment of overturning construction of towering structures.In the pretended model,the digital eigenvalues of the cloud model are used to replace the eigenvalues in the matter–element basic element,and calculate the cloud correlation of the risk assessment metrics through the correlation algorithm of the cloud model to build the computational model.Meanwhile,the improved hierarchical analysis method based on the cloud model is used to determine the weight of the index.The comprehensive evaluation scores of the evaluation event are then obtained through the weighted average method,and the safety risk level is determined accordingly.Through empirical analysis,(1)the improved hierarchical analysis method based on the cloud model can incorporate the data of multiple decisionmakers into the calculation formula to determine theweights,which makes the assessment resultsmore credible;(2)the evaluation results of the cloud-basedmatter-element coupledmodelmethod are basically consistent with those of the other two commonly used methods,and the confidence factor is less than 0.05,indicating that the cloudbased physical element coupled model method is reasonable and practical for towering structure overturning;(3)the cloud-based coupled element model method,which confirms the reliability of risk level by performing Spearman correlation on comprehensive assessment scores,can provide more comprehensive information of instances compared with other methods,and more comprehensively reflects the fuzzy uncertainty relationship between assessment indexes,which makes the assessment results more realistic,scientific and reliable. | Yingxue Sang Fengxia Han Qing Liu Liang Qiao Shouxi Wang | 2023 | Computer Modeling in Engineering & Sciences2023，，8： | 0 |
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