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1Future of anti-PD-1/PD-L1 applications: Combinations with other therapeutic regimens显示文摘Programmed cell death 1(PD-1)/programmed cell death 1 ligand(PD-L1) blockade has shown promising effects in cancer immunotherapy. Removing the so-called 'brakes' on T cell immune responses by blocking the PD-1/PDL1 check point should boost anti-tumor immunity and provide durable tumor regression for cancer patients.However, 30%–60% of patients show no response to PD-1/PD-L1 blockade. Thus, it is urgent to explore the underlying resistance mechanisms to improve sensitivity to anti-PD-1/PD-L1 therapy. We propose that the mechanisms promoting resistance mainly include T cell exclusion or exhaustion at the tumor site,immunosuppressive factors in the tumor microenvironment(TME), and a range of tumor-intrinsic factors. This review highlights the power of studying the cellular and molecular mechanisms of resistance to improve the rational design of combination therapeutic strategies that can be translated to the clinic. Here, we briefly discuss the development of PD-1/PD-L1 blockade agents and focus on the current issues and future prospects for potential combinatorial therapeutic strategies that include anti-PD-1/PD-L1 therapy, based upon the available preclinical and clinical data.Mengjia Song Xinfeng Chen Liping Wang Yi Zhang 2018Chinese Journal of Cancer Research2018,30,2:16
2Effect of various crop rotations on rice yield and nitrogen use efficiency in paddy–upland systems in southeastern China显示文摘To evaluate the effects of various rotation systems on rice grain yield and N use efficiency, a paddy–upland cropping experiment(2013–2016) was conducted in southeastern China. The experiment was designed using six different rice––winter crop rotations: rice–fallow(RF),rice–wheat(RW), rice–potato with rice straw mulch(RP), rice–green manure(Chinese milk vetch; RC–G), rice–oilseed rape(RO), and rice–green manure crop(oilseed rape with fresh straw incorporated into soil at flowering; RO–G) and three N rates, N0(0 kg N ha-1), N1(142.5 kg N ha-1), and N2(202.5 kg N ha-1). Average rice yields in the RF(5.93 t ha-1) rotation were significantly lower than those in the rotations with winter crops(7.20–7.48 t ha-1)under the N0 treatment, suggesting that incorporation of straw might be more effective for increasing soil N than winter fallow. The rice yield differences among the rotations varied by year with the N input. In general, the grain yields in the RP and RO–G rotations –were respectively 11.6–28.5% and 14.80–37.19% higher than those in the RF in plots with N applied. Increasing the N rate may have tended to minimize the average yield gap between the RF and the other rotations; the yield gaps were 18.55%, 4.14%, and 0.23% in N0, N1, and N2, respectively. However, the N recovery efficiency in the RF was significantly lower than that in other rotations, except for 2015 under both N1 and N2 rates, a finding that implies a large amount of chemical N loss. No significant differences in nitrogen agronomic efficiency(NAE) and physiological efficiency(NPE) were found between the rotations with legume(RC–G) and non–legume(RO and RW) winter crops, a result that may be due partly to straw incorporation. For this reason, we concluded that the return of straw could reduce differences in N use efficiency between rotations with and without legume crops. The degree of synchrony between the crop N demand and the N supply was evaluated by comparison of nitrogen balance degree(NBD) values. The NBD values in the RP and RW were significantly lower than those in the other rotations under both N1 and N2 rates. Thus,in view of the higher grain yield in the RP compared to the RW under the N1 rate, the RP rotation might be a promising practice with comparable grain yield and greater N use efficiency under reduced N input relative to the other rotations. The primary yield components of the RF and RP were identified as number of panicles m-2 and numbers of kernels panicle-1, respectively. The NAE and NPE were positively correlated with harvest index, possibly providing a useful indicator for evaluating N use efficiency.Song Chen Shaowen Liu Xi Zheng Min Yin Guang Chu Chunmei Xu Jinxiang Yan Liping Chen Danying Wang Xiufu Zhang 2018The Crop Journal2018,6,6:13
3Endovascular therapy for Acute ischemic Stroke Trial (EAST): study protocol for a prospective, multicentre control trial in China显示文摘Background and purpose:5 recent trials have shown the benefit of endovascular treatment for acute ischaemic stroke(AIS)due to large vessel occlusion of the anterior circulation.This study aims to evaluate the safety and efficacy of Solitaire thrombectomy in patients with moderate-to-severe stroke in the Chinese population,which has a high prevalence of intracranial atherosclerosis.Methods and analysis:This multicentre prospective control study will involve 17 stroke centres in China,and plans to recruit 150 patients in the intervention group,and 150 patients in the medical group,in which patients meet enrolment criteria but refuse intervention.Patients with AIS due to large vessel occlusion indicated for treatment with Solitaire stent retriever within 12 hours of symptom onset,and who meet the inclusion and exclusion criteria,will be enrolled in this study.The primary efficacy endpoint is functional independence as defined by a modified Rankin Scale(mRS)score≤2 at 90 days or by functional improvement as defined by mRS,using shift analysis.The procedural efficacy endpoint is arterial recanalisation of the occluded target vessel measured by a modified Thrombolysis in Cerebral Infarction(mTICI)score equal or superior to 2b right following the use of the study device.The primary safety endpoint is symptomatic intracranial haemorrhage(sICH)within 24±3 hours postprocedure.Ethics and dissemination:The protocol was approved by the Ethics Committee at the coordinating centre and by the local Institutional Review Board of each participating centre.Trial registration number:NCT02350283.Zhongrong Miao Xiaochuan Huo Feng Gao Xiaoling Liao Chunjuan Wang Ya Peng Yibin Cao Shengli Chen Meng Zhang Changchun Jiang Xiaoxiang Peng Cunfeng Song Liping Wei Qiyi Zhu Zaiyu Guo Li Liu Hang Lin Hua Yang Wei Wu Hui Liang Anding Xu Kangning Chen Xingquan Zhao Yuesong Pan Hao Li Liping Liu Yilong Wang Yongjun Wang EAST investigators 2016Stroke & Vascular Neurology2016,1,2:8
4Microstructure and Thermal Conductivity of As-Cast and As-Solutionized Mg–Rare Earth Binary Alloys显示文摘The microstructure and thermal conductivity of four groups of Mg–rare earth(RE) binary alloys(Mg–Ce,Mg–Nd, Mg–Y and Mg–Gd) in as-cast and as-solutionized states were systematically studied. Thermal conductivity was measured on a Netzsch LFA457 using laser flash method at room temperature. Results indicated that for as-cast alloys, the volume fraction of second phases increased with the increase of alloying elements. After solutionizing treatment, a part or most of second phases were dissolved in α-Mg matrix, except for Mg–Ce alloys. The thermal conductivity of as-cast and as-solutionized Mg–RE alloys decreased with the increase of concentrations. The thermal conductivity of as-solutionized Mg–Nd,Mg–Y and Mg–Gd alloys was lower than that of as-cast alloys. Thermal conductivity of as-solutionized Mg–Ce alloys was higher than that of as-cast alloys, because of the elimination of lattice defects and fine dispersed particles during solutionizing treatment. Different RE elements have different influences on the thermal conductivity of Mg alloys in the following order: Ce < Nd < Y < Gd. Ce has the minimum effect on thermal conductivity of Mg alloys, because of the very low solubility of Ce in the α-Mg matrix. The variations in the atomic radius of the solute elements with Mg atom( r), valence, configuration of extranuclear electron of the solute atoms, and the maximum solid solubility of elements in the α-Mg matrix were suggested to be the main reasons for the differences in thermal conductivity of resulting Mg–RE alloys.Liping Zhong Jian Peng Song Sun Yongjian Wang Yun Lu Fusheng Pan 2017Journal of Materials Science & Technology2017,33,11:7
5miR-486 sustains NF-KB activity by disrupting multiple NF-KB-negative feedback loops显示文摘Libing Song Chuyong Lin Hul Gong Chanjuan Wang Liping Liu Jueheng Wu Sha Tao Bo Hu Shi-Yuan Cheng Mengfeng Li Jun Li 2013Cell Research2013,23,2:6
6Overexpression of CmMYB15 provides chrysanthemum resistance to aphids by regulating the biosynthesis of lignin显示文摘MYB transcription factors are widely involved in the development of and physiological processes in plants.Here,we isolated the chrysanthemum R2R3-MYB family transcription factor CmMYB15,a homologous gene of AtMYB15.It was demonstrated that CmMYB15 expression was induced by aphids and that CmMYB15 could bind to AC elements,which usually exist in the promoter of lignin biosynthesis genes.Overexpression of CmMYB15 in chrysanthemum enhanced the resistance of aphids.Additionally,the content of lignin and the expression of several lignin biosynthesis genes increased.In summary,the results indicate that CmMYB15 regulates lignin biosynthesis genes that enhance the resistance of chrysanthemum to aphids.Cong An Liping Sheng Xinping Du Yinjie Wang Yi Zhang Aiping Song Jiafu Jiang Zhiyong Guan Weimin Fang Fadi Chen Sumei Chen 2019Horticulture Research2019,6,1:6
7Rhizosphere Aeration Improves Nitrogen Transformation in Soil, and Nitrogen Absorption and Accumulation in Rice Plants显示文摘Two rice cultivars(Xiushui 09 and Chunyou 84)were used to evaluate the effects of various soil oxygen(O2)conditions on soil nitrogen(N)transformation,absorption and accumulation in rice plants.The treatments were continuous flooding(CF),continuous flooding and aeration(CFA),and alternate wetting and drying(AWD).The results showed that the AWD and CFA treatments improved soil N transformation,rice growth,and N absorption and accumulation.Soil NO3–content,nitrification activity and ammonia-oxidising bacteria abundance,leaf area,nitrate reductase activity,and N absorption and accumulation in rice all increased in both cultivars.However,soil microbial biomass carbon and pH did not significantly change during the whole period of rice growth.Correlation analysis revealed a significant positive correlation between the nitrification activity and ammonia-oxidising bacteria abundance,and both of them significantly increased as the total N accumulation in rice increased.Our results indicated that improved soil O2 conditions led to changing soil N cycling and contributed to increases in N absorption and accumulation by rice in paddy fields.XU Chunmei CHEN Liping CHEN Song CHU Guang WANG Danying ZHANG Xiufu 2020Rice science2020,27,2:6
8Hepatitis C Virus Infection Downregulates the Ligands of the Activating Receptor NKG2D显示文摘Natural killer (NK) cells are a major component of the host innate immune defense against various pathogens. Several viruses, including hepatitis C virus (HCV), have developed strategies to evade the NK-cell response. In our study, we found HCV infection could trigger DNA damage response by both ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) pathways. Recent reports had revealed that NKG2D ligands (NK cell-activating ligands) were upregulated when a major DNA damage checkpoint pathway was activated. However, here we found that DNA damage response was activated but NKG2D ligands were downregulated upon HCV infection. Further studies showed that the protease NS3/4A of HCV which had been shown relation with immune invasion contributed to the reduced expression of NKG2D ligands. These findings provide a novel insight into the mechanisms evolved by HCV to escape from the NK cell response.Chaoyang Wen Xiang He Hongfang Ma Ningbo Hou Congwen Wei Ting Song Yanhong Zhang Liping Sun Qingjun Ma Hui Zhong 2008Cellular & Molecular Immunology2008,5,6:6
9Innovative endoscopic enucleations of the prostate--Xie’s Prostate Enucleations显示文摘In the past 2 decades,endoscopic enucleation of the prostate has become a safe and effective surgical treatment for benign prostatic hyperplasia(BPH),with comparable outcomes to traditional surgeries.Transurethral vapor enucleation and resection of the prostate(TVERP),transurethral vapor enucleation of the prostate(TVEP),and ultrasound-navigated TVEP(US-TVEP)are new,innovative endoscopic enucleation procedures.These procedures are named Xie’s Prostate Enucleations(Xie’s Procedures for short).Current clinical data indicate that Xie’s Procedures are safe and effective treatment options for patients with BPH,especially for patients with larger prostates.Further prospective,randomized clinical trials compared with traditional transurethral resection of prostate(TURP)are still needed.Liping Xie Xiao Wang Hong Chen Xiangyi Zheng Ben Liu Shiqi Li Yeqing Mao Qiqi Mao Song Wang Jiangfeng Li Tillmann Loch 2018Asian Journal of Urology2018,5,1:6
10NEDD9 promotes cancer stemness by recruiting myeloid-derived suppressor cells via CXCL8 in esophageal squamous cell carcinoma显示文摘Objective:Esophageal squamous cell carcinoma(ESCC)has high morbidity and mortality rates worldwide.Cancer stem cells(CSCs)may cause tumor initiation,metastasis,and recurrence and are also responsible for chemotherapy and radiotherapy failures.Myeloid-derived suppressor cells(MDSCs),in contrast,are known to be involved in mediating immunosuppression.Here,we aimed to investigate the mechanisms of interaction of CSCs and MDSCs in the tumor microenvironment.Methods:ESCC tissues and cell lines were evaluated.Neural precursor cell expressed,developmentally downregulated 9(NEDD9)was knocked down and overexpressed by lentiviral transfection.Quantitative PCR,Western blot,immunohistochemistry,cell invasion,flow cytometry,cell sorting,multiplex chemokine profiling,and tumor growth analyses were performed.Results:Microarray analysis revealed 10 upregulated genes in esophageal CSCs.Only NEDD9 was upregulated in CSCs using the sphere-forming method.NEDD9 expression was correlated with tumor invasion(P=0.0218),differentiation(P=0.0153),and poor prognosis(P=0.0373).Additionally,NEDD9 was required to maintain the stem-like phenotype.Screening of chemokine expression in ESCC cells with NEDD9 overexpression and knockdown showed that NEDD9 regulated C-X-C motif chemokine ligand 8(CXCL8)expression via the ERK pathway.CXCL8 mediated the recruitment of MDSCs induced by NEDD9 in vitro and in vivo.MDSCs promoted the stemness of ESCC cells through NEDD9 via the Notch pathway.Conclusions:As a marker of ESCC,NEDD9 maintained the stemness of ESCC cells and regulated CXCL8 through the ERK pathway to recruit MDSCs into the tumor,suggesting NEDD9 as a therapeutic target and novel prognostic marker for ESCC.Dongli Yue Shasha Liu Tengfei Zhang Yong Wang Guohui Qin Xinfeng Chen Huanyu Zhang Dong Wang Lan Huang Feng Wang Liping Wang Song Zhao Yi Zhang 2021Cancer Biology & Medicine2021,18,3:4
11Exposing Cu-rich {110} active facets in PtCu nanostars for boosting electrochemical performance toward multiple liquid fuels electrooxidation显示文摘In catalysis,tuning the structural composition of the metal alloy is known as an efficient way to optimize the catalytic activity.This work presents the synthesis of compositional segregated six-armed PtCu nanostars via a facile solvothermal method and their distinct composition-structure-dependent performances in electrooxidation processes.The alloy is shown to have a unique six arms with a Cu-rich dodecahedral core,mainly composed of {110} facets and exhibit superior catalytic activity toward alcohols electrooxidation compared to the hollow counterpart where Cu was selectively etched.Density functional theory (DFT) calculations suggest that the formation of hydroxyl intermediate (OH^*) is crucial to detoxify CO poisoning during the electrooxidation processes.The addition of Cu is found to effectively adjust the d band location of the alloy catalyst and thus enhance the formation of ^*OH intermediate from water splitting,which decreases the coverage of ^*CO intermediate.Our work demonstrates that the unique compositional anisotropy in alloy catalyst may boost their applications in electrocatalysis and provides a methodology for the design of this type catalyst.Liping Huang Wei Zhang Peng Li Yongbo Song Hongting Sheng Yuanxin Du Yang-Gang Wang Yuen Wu Xun Hong Yanhuai Ding Xiaoyou Yuan Manzhou Zhu 2019Nano Research2019,12,5:4
12Promotion of Mn Doped Co/CNTs Catalysts for CO Hydrogenation to Light Olefins显示文摘与各种各样的内容, Mn 被介绍进支持的碳 nanotubes ( CNT )钴催化剂和获得的 Mn-Co/CNTs 催化剂被调查让公司加氢点亮链烯并且由 N2 吸附描绘了,X光检查衍射( XRD ),X光检查光电子系列( XPS ), H2 温度规划了减小( TPR ),公司温度规划了解吸附作用( TPD )和传播电子显微镜( TEM )。结果显示到支持 CNTs 的公司催化剂的 Mn (0.3 wt%) 的小数量的增加显著地增加了 C2C4 石蜡的选择并且减少 CH4 的选择。与到钴催化剂的 Mn 的进一步的增加,然而, CH4 选择与 C5+ 选择的增加一起显然减少了。与 unpromoted 催化剂相比,支持 Mn 的钴催化剂增加了 C2C4/C20C40 臼齿的比率。Liping Tang Chengli Song Xiaolong Yang Mengli Li Bin Hu 2013Chinese Journal of Chemistry2013,31,6:4
13Enhancement of transfection efficiency for HeLa cells via incorporating arginine moiety into chitosan显示文摘Arginine-rich peptides have attracted considerable attention due to their distinct internalization mechanism. It was reported that arginine and guanidino moieties were able to translocate through cell membranes and played a critical role in the process of membrane permeation. In this work, arginine was conjugated to the backbone of chitosan to form a novel chitosan derivative, arginine modified chitosan (Arg-CS). Arg-CS/DNA complexes were prepared according to the method of coacervation process. The physicochemical properties of Arg-CS and Arg-CS/DNA complexes were characterized and the transfection activity and efficiency mediated by Arg-CS/DNA complexes were investigated taking HeLa cells as target cells. Arg-CS was characterized by FTIR and 13C NMR. Arg-CS/DNA polye- lectrolyte complexes were investigated by agarose gel retardation, dynamic light scattering (DLS) and atomic force microscopy (AFM). The results revealed that the Arg-CS/DNA complexes started to form at N/P ratio of 2:1, and the size of particles varied from 100 to 180 nm. The cytotoxicity of Arg-CS and their complexes with plasmid DNA were determined by MTT assay for HeLa cells, and the results suggested that Arg-CS/DNA complexes were slightly less toxic than Arg-CS. Moreover, the derivative alone and their complexes showed significantly lower toxicity than PEI and PEI/DNA complexes, respectively. Taking HeLa cells as target cells and using pGL3-control as reporter gene, the luciferase expression mediated by Arg-CS was greatly enhanced to about 100 folds compared with the luciferase expression mediated by chitosan at different pH media. These results suggest that Arg-CS is a promising candi- date as a safe and efficient vector for gene delivery and transfection.ZHU DunWan ZHANG HaiLing BAI JinGen LIU WenGuang LENG XiGang SONG CunXian YANG Jian LI XiaoWei JIN Xu SONG LiPing LIU LanXia LI XiuLan ZHANG Yang YAO KangDe 2007Chinese Science Bulletin2007,52,23:4
14The combination of chidamide with the CHOEP regimen in previously untreated patients with peripheral T-cell lymphoma: a prospective, multicenter, single arm, phase 1b/2 study显示文摘Objective:To assess the efficacy and safety of the novel histone deacetylase inhibitor,chidamide,in combination with cyclophosphamide,doxorubicin,vincristine,etoposide,and prednisone(Chi-CHOEP)for untreated peripheral T-cell lymphoma(PTCL).Methods:A prospective,multicenter,single arm,phase 1 b/2 study was conducted.A total of 128 patients with untreated PTCL(18–70 years of age)were enrolled between March 2016 and November 2019,and treated with up to 6 cycles with the Chi-CHOEP regimen.In the phase 1 b study,3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximumtolerated dose and recommended phase 2 dose(RP2 D).The primary endpoint of the phase 2 study was 2-year progression-free survival(PFS).Results:Fifteen patients were enrolled in the phase 1 b study and the RP2 D for chidamide was determined to be 20 mg,twice a week.A total of 113 patients were treated at the RP2 D in the phase 2 study,and the overall response rate was 60.2%,with a complete response rate of 40.7%.At a median follow-up of 36 months,the median PFS was 10.7 months,with 1-,2-,and 3-year PFS rates of 49.9%,38.0%,and 32.8%,respectively.The Chi-CHOEP regimen was well-tolerated,with grade 3/4 neutropenia occurring in approximately two-thirds of the patients.No unexpected adverse events(AEs)were reported and the observed AEs were manageable.Conclusions:This large cohort phase 1 b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.Wei Zhang Liping Su Lihong Liu Yuhuan Gao Quanshun Wang Hang Su Yuhuan Song Huilai Zhang Jing Shen Hongmei Jing Shuye Wang Xinan Cen Hui Liu Aichun Liu Zengjun Li Jianmin Luo Jianxia He Jingwen Wang O.A.O’Connor Daobin Zhou 2021Cancer Biology & Medicine2021,18,3:4
15Prognostic value of MET, cyclin D1 and MET gene copy number in non-small cell lung cancer显示文摘The aim of this study was to analyze the correlation of the expression of MET and cyclin D1 and MET gene copy number in non-small cell lung cancer (NSCLC) tissues and patient clinicopathologic characteristics and survival. Sixty-one NSCLC tissue specimens were included in the study. The expression of MET and cyclin D1 was evaluated by immunohistochemistry and MET gene copy number was assessed by quantitative real-time polymerase chain reaction (Q-PCR). Positive expression of MET and cyclin D1 protein and increased MET gene copy number occurred in 59.0%, 59.0% and 18.0% of 61 NSCLC tissues, respectively. MET-positivity correlated with poor differentiation (P=0.009). Increased MET gene copy number was significantly associated with lymph node metastasis (P=0.004) and advanced tumor stage (P=0.048), while the expression of cyclin D1 was not associated with any clinicopathologic parameters. There was a significant correlation between the expression of MET and MET gene copy number (P=0.002). Additionally, the expression of cyclin D1 had a significant association with the expression of MET as well as MET gene copy number (P=0.002 and P=0.017, respectively). MET-positivity and increased MET gene copy number were significantly associated with poor overall survival (P=0.003 and P<0.001, respectively) in univariate analysis. Multivariate Cox proportional hazard analysis confirmed that the expression of MET and MET gene copy number were prognostic indicators of NSCLC (P=0.003 and P=0.001, respectively). The overexpression of MET and the increased MET gene copy number might be adverse prognostic factors for NSCLC patients. The activation of the MET/cyclin D1 signaling pathway may contribute to carcino- genesis and the development of NSCLC, and may represent a target for therapy.Wenze Sun Liping Song Ting Ai Yingbing Zhang Ying Gao Jie Cui 2013The Journal of Biomedical Research2013,27,3:3
16Spatiotemporal distribution characteristics of the fog regions in China显示文摘The spatial distribution and monthly/annual variation of foggy days in China are analyzed based on the monthly mean fog data collected from 604 observational stations for the period 1961–2000. Results show that there are six fog regions in China: the middle reaches of the Yangtze River, coastal areas, Yunnan-Guizhou Plateau, eastern Gansu–Shaanxi region, Huaihe River valley, Tianshan mountainous area and northern Xinjiang. On the whole the interannual variation trend of foggy days is descending, especially an obvious decline after the 1980s. The areas where the foggy days have obvious tendency present a southwest-northeast direction. The rising trend regions alternate with descending trend regions, forming a SE-NW directional wave structure. In general, the number of foggy days in autumn and winter is larger than in spring and summer over most fog regions. The monthly variation curves of foggy days are bimodal in the coastal area of the Yellow Sea and northern Xinjiang, and unimodal in other regions.WANG Liping CHEN Shaoyong DONG Anxiang SONG Lianchun 2006Journal of Geographical Sciences2006,16,3:3
17Study of K/Mn-MgO Supported Fe Catalysts with Fe(CO)5 and Fe(NO3)3 as Precursors for CO Hydrogenation to Light Alkenes显示文摘二 K/Mn-MgO 支持了催化剂被 Fe (公司) 准备 5 并且 Fe (NO3 ) 3 是先锋分别地。获得的 Fe-K/Mn-MgO 催化剂被测试让公司加氢点亮链烯并且由 X 光检查描绘了粉末衍射(XRD ) , X 光检查光电子系列(XPS ) , H2 规划温度的减小(H2-TPR ) , H2,公司和 CO2 规划温度的解吸附作用(H2, CO/CO2-TPD ) 并且传播电子显微镜(TEM ) 。结果显示有装载的 10 wt% Fe 的催化剂由 Fe (公司) 准备了 5 当先锋显示了在 syngas 的更好的性能比从 Fe (NO3 ) 获得的点亮链烯 3 作为先锋,在 CO 变换是 62.50% ,选择在 350 摀畲獧是 55.95% 的地方吗?Liping Tang Chengli Song Mengli Li Xiaolong Yang Bin Hu 2013Chinese Journal of Chemistry2013,31,10:3
182022 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 2023Cancer Biology & Medicine2023,20,2:3
19Identification of Nonstructural Protein 8 as the N-Terminus of the RNA-Dependent RNA Polymerase of Porcine Reproductive and Respiratory Syndrome Virus显示文摘Porcine reproductive and respiratory syndrome virus (PRRSV) is a member within the family Arteriviridae of the order Nidovirales. Replication of this positive-stranded RNA virus within the host cell involves expression of viral replicase proteins encoded by two ORFs, namely ORF1 a and ORF1 b. In particular, translation of ORF1 b depends on a-1-ribosomal frameshift strategy. Thus, nonstructural protein 9 (nsp9), the first protein within ORF1 b that specifies the function of the viral RNA-dependent RNA polymerase, is expressed as the C-terminal extension of nsp8, a small nsp that is encoded by ORF1 a. However, it has remained unclear whether the mature form of nsp9 in virus-infected cells still retains nsp8,addressing which is clearly critical to understand the biological function of nsp9. By taking advantage of specific antibodies to both nsp8 and nsp9, we report the following findings. (1) In infected cells, PRRSV nsp9 was identified as a major product with a size between 72 and 95 k Da (72–95 KDa form), which exhibited the similar mobility on the gel to the in vitro expressed nsp8–9 ORF1 b, but not the ORF1 b-coded portion (nsp9 ORF1 b). (2) The antibodies to nsp8, but not to nsp7 or nsp10, could detect a major product that had the similar mobility to the 72–95 KDa form of nsp9. Moreover, nsp9 could be co-immunoprecipitated by antibodies to nsp8, and vice versa. (3) Neither nsp4 nor nsp2 PLP2 was able to cleave nsp8–nsp9 in vitro. Together, our studies provide experimental evidence to suggest that nsp8 is an N-terminal extension of nsp9.Our findings here paves way for further charactering the biological function of PRRSV nsp9.Yuanyuan Liu Yunhao Hu Yue Chai Liping Liu Jiangwei Song Shaochuan Zhou Jia Su Lei Zhou Xinna Ge Xin Guo Jun Han Hanchun Yang 2018Virologica Sinica2018,33,5:3
20Influenza A virus-induced downregulation of miR-26a contributes to reduced IFNα/β production显示文摘Innate immunity provides immediate defense against viral infection. Influenza A virus(IAV) is able to get past the first line of defense. Elucidation of the molecular interaction between influenza factors and the newly recognized host players in the innate response might help in our understanding of the root causes of virulence and pathogenicity of IAV. In this study, we show that expression of miR-26 a leads to a significant inhibition of IAV replication. miR-26 a does not directly target IAV genome. Instead, miR-26 a activates the type I interferon(IFN) signaling pathway and promotes the production of IFN-stimulated genes, thus suppressing viral replication. Furthermore,ubiquitin-specific protease 3(USP3), a negative regulator of type I IFN pathway, is targeted by miR-26 a upon IAV challenge. However, miR-26 a is significantly downregulated during IAV infection.Thus, downregulation of miR-26 a is a new strategy evolved by IAV to counteract cellular antiviral responses. Our findings indicate that delivery of miR-26 a may be a potential strategy for anti-IAV therapies.Shijuan Gao Jiandong Li Liping Song Jiaoxiang Wu Wenlin Huang 2017Virologica Sinica2017,32,4:3
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