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| 1 | Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing,locally advanced or metastatic gastric or gastroesophageal junction cancer:a single-arm phase II study显示文摘Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy. | Zhi Peng Tianshu Liu Jia Wei Airong Wang Yifu He Liuzhong Yang Xizhi Zhang Nanfeng Fan Suxia Luo Zhen Li Kangsheng Gu Jianwei Lu Jianming Xu Qingxia Fan Ruihua Xu Liangming Zhang Enxiao Li Yuping Sun Guohua Yu Chunmei Bai Yong Liu Jiangzheng Zeng Jieer Ying Xinjun Liang Nong Xu Chao Gao Yongqian Shu Dong Ma Guanghai Dai Shengmian Li Ting Deng Yuehong Cui Jianmin Fang Yi Ba Lin Shen | 2021 | Cancer Communications2021，41，11： | 29 |
| 2 | Defined tumor antigen-specific T cells potentiate personalized TCR-T cell therapy and prediction of immunotherapy response显示文摘Personalized immunotherapy targeting tumor-specific antigens(TSAs)could generate efficient and safe antitumor immune response without damaging normal tissues.Although neoantigen vaccines have shown therapeutic effect in clinic trials,precise prediction of neoantigens from tumor mutations is still challenging.The host antitumor immune response selects and activates T cells recognizing tumor antigens.Hence,T cells engineered with T-cell receptors(TCRs)from these naturally occurring tumor antigen-specific T(Tas)cells in a patient will target personal TSAs in his/her tumor.To establish such a personalized TCR-T cell therapy,we comprehensively characterized T cells in tumor and its adjacent tissues by single-cell mRNA sequencing(scRNA-seq),TCR sequencing(TCR-seq)and in vitro neoantigen stimulation.Compared to bystander T cells circulating among tissues,Tas cells were characterized by tumor enrichment,tumor-specific clonal expansion and neoantigen specificity.We found that CXCL13 is a unique marker for both CD4^(+)and CD8^(+)Tas cells.Importantly,TCR-T cells expressing TCRs from Tas cells showed significant therapeutic effects on autologous patient-derived xenograft(PDX)tumors.Intratumoral Tas cell levels measured by CXCL13 expression precisely predicted the response to immune checkpoint blockade,indicating a critical role of Tas cells in the antitumor immunity.We further identified CD200 and ENTPD1 as surface markers for CD4^(^(+))and CD8^(^(+))Tas cells respectively,which enabled the isolation of Tas cells from tumor by Fluorescence Activating Cell Sorter(FACS)sorting.Overall,our results suggest that TCR-T cells engineered with Tas TCRs are a promising agent for personalized immunotherapy,and intratumoral Tas cell levels determine the response to immunotherapy. | Jingjing He Xinxin Xiong Han Yang Dandan Li Xuefei Liu Shuo Li Shuangye Liao Siyu Chen Xizhi Wen Kuai Yu Lingyi Fu Xingjun Dong Kaiyu Zhu Xiaojun Xia Tiebang Kang Chaochao Bian Xiang Li Haiping Liu Peirong Ding Xiaoshi Zhang Zhenjiang Liu Wende Li Zhixiang Zuo Penghui Zhou | 2022 | Cell Research2022，32，6： | 10 |
| 3 | The zinc transporter Slc39a5 controls glucose sensing and insulin secretion in pancreatic β-cells via Sirt1- and Pgc-1α-mediated regulation of Glut2显示文摘Zinc levels are high in pancreatic β-cells, and zinc is involved in the synthesis, processing and secretion of insulin in these cells. However, precisely how cellular zinc homeostasis is regulated in pancreatic β-cells is poorly understood. By screening the expression of 14 Slc39a metal importer family member genes, we found that the zinc transporter Slc39a5 is significantly downregulated in pancreatic β-cells in diabetic db/db mice, obese ob/ob mice and high-fat diet-fed mice. Moreover,β-cell-specific Slc39a5 knockout mice have impaired insulin secretion. In addition, Slc39a5-deficient pancreatic islets have reduced glucose tolerance accompanied by reduced expression of Pgc-1α and its downstream target gene Glut2. The down-regulation of Glut2 in Slc39a5-deficient islets was rescued using agonists of Sirt1, Pgc-1α and Ppar-γ. At the mechanistic level, we found that Slc39a5-mediated zinc influx induces Glut2 expression via Sirt1-mediated Pgc-1α activation. These findings suggest that Slc39a5 may serve as a possible therapeutic target for diabetes-related conditions. | Xinhui Wang Hong Gao Wenhui Wu Enjun Xie Yingying Yu Xuyan He Jin Li Wanru Zheng Xudong Wang Xizhi Cao Zhuoxian Meng Ligong Chen Junxia Min Fudi Wang | 2019 | Protein & Cell2019，10，6： | 6 |
| 4 | The solute carrier transporters and the brain:Physiological and pharmacological implications显示文摘Solute carriers(SLCs)are the largest family of transmembrane transporters that determine the exchange of various substances,including nutrients,ions,metabolites,and drugs across biological membranes.To date,the presence of about 287 SLC genes have been identified in the brain,among which mutations or the resultant dysfunctions of 71 SLC genes have been reported to be correlated with human brain disorders.Although increasing interest in SLCs have focused on drug development,SLCs are currently still under-explored as drug targets,especially in the brain.We summarize the main substrates and functions of SLCs that are expressed in the brain,with an emphasis on selected SLCs that are important physiologically,pathologically,and pharmacologically in the blood-brain barrier,astrocytes,and neurons.Evidence suggests that a fraction of SLCs are regulated along with the occurrences of brain disorders,among which epilepsy,neurodegenerative diseases,and autism are representative.Given the review of SLCs involved in the onset and procession of brain disorders,we hope these SLCs will be screened as promising drug targets to improve drug delivery to the brain. | Chengliang Hu Lei Tao Xizhi Cao Ligong Chen | 2020 | Asian Journal of Pharmaceutical Sciences2020，15，2： | 6 |
| 5 | Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels显示文摘Brachydactyly 打 A1 (BDA1 ) ,第一在人记录了孟德尔的正染色体的主导的混乱,被弄短或中间的指骨的缺席描绘。在印度刺猬(IHH ) 基因的异质接合的错误感觉变化作为 BDA1 的一个原因被识别了;然而,这些变化的生物化学的后果是不清楚的。在这份报纸,我们在印度刺猬(IhhN ) 的 N 终端碎片分析了三个 BDA1 变化(E95K, D100E,和 E131K ) 。结构的分析证明 E95K 变化在一条钙绑定沟把一个否定地控告的区域改变到一个断然控告的区域,并且 D100E 变化改变本地第三级的结构。而且,我们证明 E95K 和 D100E 变化导致了一温度敏感并且 IhhN 的钙依赖者不稳定性,它可能经由 lysosome 贡献变异的蛋白质的提高的细胞内部的降级。尤其是,所有三个变化影响了对受体 Patched1 (PTC1 ) 有约束力的 Hh,减少它的能力导致细胞的区别。我们建议这些是引起 BDA1 的变化的普通特征,影响 Hh 第三级的结构,细胞内部的命运,到受体 / 搭挡的绑定,和到细胞外的部件的绑定。这些特征的联合改变发信号的能力和范围,但是影响是可能的是变量和变化依赖者。在发信号的范围的潜在的变化被和 heparan 硫酸盐的一个提高的相互作用与 E95K 变化,然而并非 E131K 变化为 IHH 描绘。一起拿,我们的结果建议这些 IHH 变化影响在多重层次,引起的反常骨头发展和反常的位形成发信号的 Hh。 | Gang Ma Jiang Yu Yue Xiao Danny Chan Bo Gao Jianxin Hu Yongxing He Shengzhen Guo Jian Zhou Lingling Zhang Linghan Gao Wenjuan Zhang Yan Kang Kathryn SE Cheah Guoyin Feng Xizhi Guo Yujiong Wang Cong-zhao Zhou Lin He | 2011 | Cell Research2011，21，9： | 6 |
| 6 | PEGylated mBPEI-rGO nanocomposites facilitate hepotocarcinoma treatment combining photothermal therapy and chemotherapy显示文摘Despite chemotherapy has been widely used for tumor therapy, the serious side effect is still a major challenge. Recently, two dimensional nanomaterial-based drug delivery systems have attracted wide concern due to their high drug loading and low side effect. In addition, some kinds of nanomaterials can directly act as a photosensitizer to induce cancer destruction. In this study, we developed a drug delivery system of mixture of high/low molecular weight branched polyethylenimine-polyethylene glycol-reduced graphene oxide(mBPEI-PEG-rGO) using reduced graphene oxide as matrix. A model drug of doxorubicin(DOX) was loaded on the nanocomposites with the efficiency of 81% and the release rate of more than 50% at acidic environment. In vitro experiments indicated that mBPEI-PEG-rGO-DOX with enhanced stability and biocompatibility efficiently delivered and released DOX into cells mainly through micropinocytosis and killed SMMC-7721 cells by inducing reactive oxygen species(ROS) and cell apoptosis. Furthermore, in vivo experiments indicated that the combination of intratumoral injection of mBPEI-PEG-rGO-DOX and local laser irradiation nearly ablated hepatocarcinoma. In conclusion, this new drug delivery system provided an alternative for combinational photothermal and chemotherapy against hepatocarcinoma. | Chunyi Tong Xizhi Zhang Jialong Fan Bin Li Bin Liu Muhammad Daniyal Wei Wang | 2018 | Science Bulletin2018，63，14： | 6 |
| 7 | Effects of Shrub on Runoff and Soil Loss at Loess Slopes Under Simulated Rainfall显示文摘Improved understanding of the effect of shrub cover on soil erosion process will provide valuable information for soil and water conservation programs.Laboratory rainfall simulations were conducted to determine the effects of shrubs on runoff and soil erosion and to ascertain the relationship between the rate of soil loss and the runoff hydrodynamic characteristics.In these simulations a 20° slope was subjected to rainfall intensities of 45,87,and 127 mm/h.The average runoff rates ranged from 0.51 to 1.26 mm/min for bare soil plots and 0.15 to 0.96 mm/min for shrub plots.Average soil loss rates varied from 44.19 to 114.61 g/(min·m^2) for bare soil plots and from 5.61 to 84.58 g/(min·m^2) for shrub plots.There was a positive correlation between runoff and soil loss for the bare soil plots,and soil loss increased with increased runoff for shrub plots only when rainfall intensity is 127 mm/h.Runoff and soil erosion processes were strongly influenced by soil surface conditions because of the formation of erosion pits and rills.The unit stream power was the optimal hydrodynamic parameter to characterize the soil erosion mechanisms.The soil loss rate increased linearly with the unit stream power on both shrub and bare soil plots.Critical unit stream power values were 0.004 m/s for bare soil plots and 0.017 m/s for shrub plots. | XIAO Peiqing YAO Wenyi SHEN Zhenzhou YANG Chunxia LYU Xizhi JIAO Peng | 2017 | Chinese Geographical Science2017，27，4： | 5 |
| 8 | β-catenin activation in hair follicle dermal stem cells in duces ectopic hair outgrowth and skin fibrosis显示文摘Hair follicle dermal sheath(DS)harbors hair follicle dermal stem cells(hfDSCs),which can be recruited to replenish DS and dermal papilla(DP).Cultured DS cells can differentiate into various cell lineages in vitro.However,it is unclear how its plasticity is modulated in vivo.Wnt/β-catenin signaling plays an important role in maintaining stem cells of various lineages and is required for HF development and regeneration.Here we report that activation ofβ-catenin in DS generates ectopic HF outgrowth(EF)by reprogramming HF epidermal cells and DS cells themselves,and endows DS cells with hair inducing ability.Epidermal homeostasis of pre-existing HFs is disrupted.Additionally,cell-autonomous progressive skin fibrosis is prominent in dermis,where the excessive fibroblasts largely originate from DS.Gene expression analysis of purified DS cells with activatedβ-catenin revealed significantly increased expression of Bmp,Fgf,and Notch ligands and administration of Bmp,Fgf,or Notch signaling inhibitor attenuates EF formation.In summary,our findings advance the current knowledge of high plasticity of DS cells and provide an insight into understanding how Wnt/β-catenin signaling controls DS cell behaviors. | Yixin Tao Qingchun Yang Lei Wang Jie Zhang Xuming Zhu Qianqian Sun Yunbin Han Qian Luo Yushu Wang Xizhi Guo Ji Wu Baojie Li Xiao Yang Lin He Gang Ma | 2019 | Journal of Molecular Cell Biology2019，11，1： | 4 |
| 9 | Study of seismic behavior of PHC piles with partial normal-strength deformed bars显示文摘Nine PHC piles with partial normal-strength deformed bars were prepared in present study,and cyclic loading tests were implemented to evaluate these piles’seismic performance.The influence of the axial compression ratio and the amount of normal-strength deformed bars on failure modes,crack patterns,strength,stiffness,and ductility were examined.The test findings indicate that the change of axial compression ratio has a noticeable influence on the failure mode of PHC piles.A larger axial compression ratio results in a higher cracking bending resistance,ultimate bending resistance,and initial stiffness,but the propagation heights of flexural cracks decrease as the axial compression ratio increases.Furthermore,increasing the amount of normal-strength deformed bars causes a slight decrease in ductility.Finally,a calculation formula was proposed to predict the flexural capacity of PHC piles with partial normal-strength deformed bars. | Zhang Xizhi Zhang Shaohua Xu Shengbo Niu Sixin | 2020 | Earthquake Engineering and Engineering Vibration2020，19，2： | 3 |
| 10 | The causes and processes responsible for rocky desertification in karst areas of southern China显示文摘The karst region of southern China is a fragile ecological zone with widespread rocky desertification. This paper describes the rocky desertification occurring in this region in terms of both natural and anthropogenic factors. During geological time periods, the region's changing environment governed the natural rocky desertification processes, whereas during historical and modern times, anthropogenic processes have been superimposed on these natural processes. Human activities have accelerated and exacerbated rocky desertification. The period from the beginning to the middle of the Qing dynasty was an important transitional period in which human activities began to exert a particularly strong influence on rocky desertification. Since then, the effect of anthropogenic factors has increasingly exceeded the effect of natural factors. The rocky desertification process in southern China's karst region combines surface ecological processes (including vegetation degradation and loss, soil erosion, surface water loss, and bedrock solution) with a reduction of the land's biological productivity, leading to degradation that produces rocky desert. Controlling rocky desertification requires comprehensive development of sustainable agriculture and economic development that provides employment alternatives to agriculture and thereby promotes the rehabilitation of rocky desertified land. | Sen Li 1,2*, XingHu Wei 1, JinGuo Huang 1, XiZhi Wang 1, GuanYao Lu 1, HuiXia Li 11. Institute of Resources and Environment Science, Foshan University, Foshan, Guangdong 528000, China.2. College of Geography and Environment Science, Northwest Normal University, Lanzhou, Gansu 730070, China. | 2009 | Research in Cold and Arid Regions2009，1，1： | 3 |
| 11 | Characterization of a novel missense mutation on murine Pax3 through ENU mutagenesis显示文摘N-ethyl-N-nitrosourea (ENU ) mutagenesis 为 melanocyte 和皮肤开发导致了几管理者基因的说明。这里,我们作为斑点异种的与类似的显型从 ENU mutagenesis 描绘了异种, exencephaly 包括,在象白肚子看到一样并且偶尔的同质接合体的棘 bifida 和反常手足在异质接合体的环尾巴。这新奇异种作为 SpxG 被说出。通过在有 microsatellite 标记的回交子孙的染色体宽的连接分析, SpxG 在染色体 1 上被限制到在 D1MIT415 和 D1MIT7 之间的一个区域,在著名 Pax3 基因被定位的地方。直接定序表明 SpxG 在 exon 带了核苷酸 A894G 错误感觉转变在在高度保存的 homeodomain (HD ) 以内的氨基酸 269 点导致了 Asn 到毒蛇替换的 6 Pax3 基因 DNA 识别模块,它第一个点变化在老鼠在这个领域被发现。这个 N269D 变化损害了 Pax3 蛋白质的 transactivation 能力,但是没在 Pax3 蛋白质翻译以后施加效果。新变化的描述扩展了我们理解 transactivation 和 Pax3 蛋白质的 DNA 有约束力的结构。 | Yue Xiao Lingling Zhang Kuanjun He Xiang Gao Lun Yang Lin He Gang Ma Xizhi Guo | 2011 | Journal of Genetics and Genomics2011，38，8： | 2 |
| 12 | Simulation of Runoff in Karst-influenced Lianjiang Watershed Using the SWAT Model显示文摘 | Xizhi Wang Zhaoxiong Liang Jun Wang | 2014 | 地球科学期刊(中英文版)2014，4，2： | 2 |
| 13 | Differentiation of Induced Pluripotent Stem Cells into Male Germ Cells In Vitro through Embryoid Body Formation and Retinoic Acid or Testosterone Induction显示文摘 | Peng Li Hongliang Hu Shi Yang Ruhui Tian Zhenzhen Zhang Wei Zhang Meng Ma Yong Zhu Xizhi Guo Yiran Huang Zuping He Zheng Li Xuan Jin | 2012 | BioMed Research International2012，，： | 2 |
| 14 | Local influence on a Selected Coefficient in Linear Regression Model 显示文摘 | Wu Xizhi Zhang Xibin | 1996 | Acta Seientiarum Naturalium Universitatis Nankaiensis1996，29，2： | 1 |
| 15 | Thermal cycling behavior and failure mechanism of La 2 (Zr 0.7 Ce 0.3 ) 2 O 7 /Eu 3+ -doped 8YSZ thermal barrier coating prepared by atmospheric plasma spraying显示文摘 | Sumei Zhao Lijian Gu Yu Zhao Wenzhi Huang Ling Zhu Xizhi Fan Binglin Zou Xueqiang Cao | 2013 | Journal of Alloys and Compounds2013，，： | 1 |
| 16 | Molecularly imprinted polymer microspheres for solid-phase extraction of chloramphenicol residues in foods显示文摘 | Shi Xizhi Wu Aibo Zheng Sulian | 2007 | Jouranl of chromatography B2007，850，： | 1 |
| 17 | Molecularly imprinted polymer microspheres for solid-phase extraction of chloramphenicol residues in foods 显示文摘 | SHI Xizhi WU Aibo ZHENG Sulian | 2007 | J Chromatogr B2007，850，12： | 1 |
| 18 | Group-selective enrichment and determination of pyrethroid insecticides in aquaculture seawater via molecularly imprinted solid phase extraction coupled with gas chromatography- electron capture detection 显示文摘 | SHI Xizhi LIU Jinghua SUN Aili | 2012 | Journal of Chromatography A2012，1227，： | 1 |
| 19 | Reactive plasma spraying synthesis and characterization of TiB 2 –TiC–Al 2 O 3 /Al composite coatings on a magnesium alloy显示文摘 | Jiaying Xu Binglin Zou Xizhi Fan Sumei Zhao Yu Hui Ying Wang Xin Zhou Xiaolong Cai Shunyan Tao Hongmei Ma Xueqiang Cao | 2014 | Journal of Alloys and Compounds2014，，： | 1 |
| 20 | Molecularly imprinted polymer microspheres for solid-phase extraction of chloramphenicol residues in foods 显示文摘 | Shi Xizhi Wu Aibo Zheng Sulian | 2007 | Journal of Chromatography B2007，850，12： | 1 |
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