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SHR-A1811(antibody-drug conjugate)in advanced HER2-mutant non-small cell lung cancer:a multicenter,open-label,phase 1/2 study

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3483-3492页

作者： Ziming Li Zhengbo Song Wei Hong Nong Yang Yongsheng Wang Hong Jian Zibin Liang Sheng Hu Min Peng Yan Yu Yan Wang Zicong Jiao Kaijing Zhao Ke Song You Li Wei Shi Shun lu Shanghai lung Cancer Center Shanghai Chest HospitalShanghai Jiaotong University School of MedicineShanghai 200030China Phase I Clinical Trial Ward Zhejiang Cancer HospitalHangzhou 310000China Department of Thoracic Oncology Zhejiang Cancer HospitalHangzhou 310000China Department of lung&Gastrointestinal Oncology Hunan Cancer HospitalChangsha 410031China Thoracic Oncology Ward/Cancer Center West China Hospital of Sichuan UniversityChengdu 610041China Department of Thoracic Oncology The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 51900China Department of Medical Oncology Hubei Cancer HospitalWuhan 43000China Department of Oncology Renmin Hospital of Wuhan UniversityWuhan 430200China Department of Thoracic Medicine Harbin Medical University Cancer HospitalHarbin 150081China Department of Medical Oncology Cancer HospitalChinese Academy of Medical SciencesBeijing 100021China Geneplus-Beijing CoLtd.Beijing 102206China Jiangsu Hengrui Pharmaceuticals Co.Ltd.Shanghai 200120China

A dose-escalation and expansion,phase 1/2 study(***,NCT04818333)was conducted to assess the novel antibodydrug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer(NSCLC).Here,we report results from the phase 1 *** who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 *** escalation followed a Bayesian logistic regression model that included overdose control,with subsequent selection of tolerable levels for dose ***,63 patients were enrolled,including 43 receiving a recommended dose for expansion of 4.8 mg/*** patients had HER2-mutant ***-limiting toxicity occurred in one patient in the 8.0 mg/kg dose ***≥3 treatment-related adverse events occurred in 29(46.0%)*** patient in the 6.4 mg/kg cohort died due to interstitial lung *** of April 11,2023,the 4.8 mg/kg cohort showed an objective response rate of 41.9%(95%Cl 27.0-57.9),and a disease control rate of 95.3%(95%Cl 84.2-99.4).The median duration of response was 13.7 months,with 13 of 18 responses *** median progression-free survival was 8.4 months(95%CI 7.1-15.0).SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutantNSCLC.

关键词： SHR HER2 doses

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Runoff Change of Naoli River in Northeast China in 1955–2009 and Its Influencing Factors

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Chinese Geographical Science 2012年第2期22卷 144-153页

作者： SONG Xiaolin lu Xianguo LIU Zhengmao sun Yonghe Key Laboratory of Wetland Ecology and Environment Northeast Institute of Geography and Agroecology Chinese Academy of Sci- ences Changchun 130012 China Graduate university of Chinese Academy of Sciences Beij＇ing 100049 China Heilongjiang Agricultural Reclamation Survey Design and Research Institute Harbin 150090 China Jiamusi Hydrological Bureau in Heilongjiang Province Jiamusi 154000 China

Runoff change and trend of the Naoli River Basin were studied through the time series analysis using the data from the hydrological and meteorological stations. Time series of hydrological data were from 1957 to 2009 for Bao′an station, from 1955 to 2009 for Baoqing station, from 1956 to 2009 for Caizuizi station and from 1978 to 2009 for Hongqiling station. The influences of climate change and human activities on runoff change were investigated, and the causes of hydrological regime change were revealed. The seasonal runoff distribution of the Naoli River was extremely uneven, and the annual change was great. Overall, the annual runoff showed a significant decreasing trend. The annual runoff of Bao′an, Baoqing, and Caizuizi stations in 2009 decreased by 64.1%, 76.3%, and 84.3%, respectively, compared with their beginning data recorded. The wet and dry years of the Naoli River have changed in the study period. The frequency of wet year occurrence decreased and lasted longer, whereas that of dry year occurrence increased. The frequency of dry year occurrence increased from 25.0%-27.8% to 83.9%-87.5%. The years before the 1970s were mostly wet, whereas those after the 1970s were mostly dry. Precipitation reduction and land use changes contributed to the decrease in annual runoff. Rising temperature and water project construction have also contributed important effects on the runoff change of the Naoli River.

关键词： runoff change hydrological parameters wetland land use human activities Naoli River

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Towards high-performance packet processing on commodity multi-cores: current issues and future directions

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Science China(Information Sciences) 2015年第12期58卷 28-43页

作者： TANG lu YAN JinLi sun ZhiGang LI Tao ZHANG MinXuan School of Computer National University of Defense Technology

The demands of programmability have become more and more exigent as novel network services appear, such as E-commerce, social softwares, and online videos. Commodity multi-core CPUs have been widely applied in network packet processing to get high programmability and reduce the time-to-market. However,there is a great gap between the packet processing performance of commodity multi-core and that of the traditional packet processing hardware, e.g., NP(Network Process). Recently, optimization of the packet processing performance of commodity multi-cores has become a hot topic in industry and academia. In this paper, based on a detailed analysis of the packet processing procedure, firstly we identify two dominating overheads, namely the virtual-to-physical address translation and the packet buffer management. Secondly, we make a comprehensive survey on the current optimization methods. Thirdly, based on the survey, the heterogeneous architecture of the commodity multi-core + FPGA is proposed as a promising way to improve the packet processing ***, a novel Self-Described Buffer(SDB) management technology is introduced to eliminate the overheads of the allocation and deallocation of the packet buffers offloaded to FPGA. Then, an evaluation testbed, named PIOT(Packet I/O Testbed), is designed and implemented to evaluate the packet forwarding performance. I/O capacity of different commodity multi-core CPUs and the performance of optimization methods are assessed and compared based on PIOT. At last, the future work of packet processing optimization on multi-core CPUs is discussed.

关键词： network commodity multi-core packet processing SKB DPDK

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STUDY ON WAKING BOAT-TYPE TRACTOR

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Chinese Journal of Mechanical Engineering 1996年第3期9卷 225-233页

作者： sun Quanying (harbin Institute of Electrical Technology)Qiu Changhua lu Huaimin (harbin Engineering university Northeast Forestry university) harbin Institute of Electrical Technology

ln order to raise the tractive efficiency of a boat-typc tractor further, according to a point of view about reducing energy consumption by reducing the volume of thc blade cavity, an idea of four-footed walkiag boat-type tractor is put forward. and a walking device with two feet and four small wheels is designed and manufactured. It can move on the rails of a paddy soil bin to simulate the tractive performance of a boat-type tractor in thc paddy field. Kinematics and dynam- ics of the walking device is analysed. Because it can ensure that the blade foot enters and leaves the soil vertically, and eliminates the functions of the soil compression and pick by the blade entirely, so the volume of the blade cavity can be reduced to a minimum and the efficiency of the walking sys- tem has been rasied considerably. Thus, it is feasible to adopt a four-footed walking mechanism in the boat-type tractor.

关键词： Boat-type tractor Walking machine Elasto-viscoplasticity Finite element analysis

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腹腔镜解剖性肝切除的发展

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中华普外科手术学杂志（电子版） 2024年第4期18卷 363-366页

作者：陆朝阳金也孙备哈尔滨医科大学附属第一医院肝脏外科肝脾外科教育部重点实验室哈尔滨150001

解性肝切除是指完整切除荷瘤门静脉流域内的肝实质,在其理论与技术操作不断完善、丰富的过程中,对于其实际疗效的质疑与争议从未停歇。先进技术的应用与普及促进肝脏外科迎来新的发展机遇,也为充实并丰富解剖性肝切除理论创造新的契机,... 详细信息

解性肝切除是指完整切除荷瘤门静脉流域内的肝实质,在其理论与技术操作不断完善、丰富的过程中,对于其实际疗效的质疑与争议从未停歇。先进技术的应用与普及促进肝脏外科迎来新的发展机遇,也为充实并丰富解剖性肝切除理论创造新的契机,有望更好实现肝细胞癌的治疗效果.

关键词：癌,肝细胞解部性肝切除门静脉流域腹腔镜肝切除

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梭鲈快速生长品系F_(3)基因型与生长性状关联分析

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上海海洋大学学报 2024年第5期33卷 1053-1063页

作者：潘亚丹鲁翠云孙志鹏刘天奇张渴新郑先虎中国水产科学研究院黑龙江水产研究所农业农村部淡水水产生物技术与遗传育种重点实验室黑龙江哈尔滨150070 上海海洋大学水产与生命学院上海201306

为了筛选可用于遗传选育的标记,用微卫星标记分析了梭鲈快速生长品系F3群体的遗传结构,评估了不同基因型与生长性状(体质量、全长、体长、体高、体厚、头长、吻长、尾柄高、尾柄长)的相关性。遗传结构评估结果显示:群体平均等位基因数为... 详细信息

为了筛选可用于遗传选育的标记,用微卫星标记分析了梭鲈快速生长品系F3群体的遗传结构,评估了不同基因型与生长性状(体质量、全长、体长、体高、体厚、头长、吻长、尾柄高、尾柄长)的相关性。遗传结构评估结果显示:群体平均等位基因数为4.5,观测杂合度为0.746(0.520~0.954),期望杂合度为0.691(0.441~0.851),平均多态信息含量为0.641(0.412~0.843),群体处于高度多态水平(PIC>0.5)。基因型与性状关联分析结果显示38个微卫星标记与至少1个性状表现出不同程度的相关性(P<0.05),其中HLJSL018、HLJSL021、HLJSL022等21个标记与相应性状的相关性达到极显著水平(P<0.01)。9个性状检测到2~21个显著相关的微卫星标记,与体长呈显著相关的标记最少(HLJSL039和HLJSL042)(P<0.05);与尾柄高呈显著相关的标记最多(21个),其中HLJSL018、HLJSL021和HLJSL022等11个标记与其呈极显著相关(P<0.01)。与体质量呈显著相关的标记有8个,其中HLJSL018和HLJSL067与其呈极显著相关(P<0.01)。以高于总体均值且比例达5%以上为优势基因型的筛选标准,在38个标记共获得195个优势基因型,每个标记获得1~10个优势基因型,其中HLJSL073获得优势基因型最少,HLJSL079获得优势基因型最多。本研究评估了梭鲈选育群体的遗传结构,获得了与性状显著相关的标记,研究结果可用于指导梭鲈遗传选育。

关键词：梭鲈基因型生长性状关联分析

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一种求解优化问题的新型小波混沌神经网络

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计算机工程与应用 2010年第11期46卷 42-45页

作者：孙明赵琳徐耀群丁继成哈尔滨工程大学自动化学院哈尔滨150001 哈尔滨商业大学自动化学院哈尔滨150028

基于神经元的自反馈项可产生混沌的现象,将Gauss小波函数作为混沌神经元的自反馈项。分析了Gauss小波的尺度和平移参数对神经元动力学的影响,提出了自反馈连接权和Gauss小波尺度双重模拟退火的混沌神经元。构建了混沌神经网络模型,分析... 详细信息

基于神经元的自反馈项可产生混沌的现象,将Gauss小波函数作为混沌神经元的自反馈项。分析了Gauss小波的尺度和平移参数对神经元动力学的影响,提出了自反馈连接权和Gauss小波尺度双重模拟退火的混沌神经元。构建了混沌神经网络模型,分析了由Gauss小波函数产生的附加能量函数对网络优化能力的影响。优化问题的仿真结果表明,该网络能够以较快的速度找到优化问题的全局最优解。

关键词： Gauss小波混沌神经网络优化问题

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Formation of Mycorrhiza-like Structures in Cultured Root/Callus of Cathaya argyrophylla Chun et Kuang Infected with the Ectomycorrhizal Fungus Cenococcum geophilum Fr.

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Journal of Integrative Plant Biology 2006年第10期48卷 1163-1167页

作者： Xue sun Yu-Hua Li lu-Min Vaario College of Life Sciences Northeast Forestry University Harbin 150040 China

An in vitro system was used for ectomycorrhizal synthesis of Cenococcum geophilum Fr. with Cathaya argyrophylla Chun et Kuang, an endangered species. Calli initiated from stem segments and adventitious roots differentiated from young seedlings were removed and cocultured with Cenococcum geophllum on a modified Murashlge-Skoog medium. Fungal hyphae were visible within intercellular spaces of the callus 4 weeks after inoculation, but definite and well-developed Hartig net structures did not form in the calu 8 weeks after inoculation. The typical ectomycorrhizal structures （i.e. hyphal mantle and Intracortical Hartig net） were observed in root segments 8 weeks after inoculation. This is the first report of aseptic ectomycorrhlzal-like formation/infection between root organ/callus of Cathaya argyrophylla and the ectomycorrhizal fungus Cenococcum geophflum. This culture system is useful for further investigation of mycorrhizal synthesis in Cathaya trees.

关键词： ectomycorrhiza endangered pine Hartig net in vitro

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基于UPLC-Q-TOF-MS分析大麻二酚对肺纤维化的影响

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中国实验方剂学杂志 2024年第12期30卷 185-193页

作者：孙梦迪张飞宇杨慧聪王宇陈平平卢芳刘树民黑龙江中医药大学中医药研究院哈尔滨150040

目的:应用超高效液相色谱-四极杆-飞行时间质谱法(UPLC-Q-TOF-MS)进行肺组织代谢组学分析,探讨大麻二酚抗肺纤维化的作用机制。方法:将48只SD大鼠随机分为空白组、模型组、泼尼松组(3.15 mg·kg^(-1))、大麻二酚低、中、高剂量组(12、36... 详细信息

目的:应用超高效液相色谱-四极杆-飞行时间质谱法(UPLC-Q-TOF-MS)进行肺组织代谢组学分析,探讨大麻二酚抗肺纤维化的作用机制。方法:将48只SD大鼠随机分为空白组、模型组、泼尼松组(3.15 mg·kg^(-1))、大麻二酚低、中、高剂量组(12、36、108 mg·kg^(-1)),每组8只。除空白组外,各组均通过气管内注射5 mg·kg^(-1)博来霉素构建肺纤维化大鼠模型,造模成功后各组按剂量每天灌胃给药1次,空白组灌胃等量生理盐水,连续给药28 d。观察大鼠肺组织病理变化,酶联免疫吸附测定法(ELISA)检测血清中基质金属蛋白酶-7(MMP-7)、Ⅱ型肺泡细胞表面抗原(KL-6)、肺表面活性物质相关蛋白A(SP-A)、肺表面活性物质相关蛋白D(SP-D)的表达水平,免疫组化检测肺组织Ⅰ型胶原蛋白(Col-Ⅰ)、纤维连接蛋白(FN)的表达水平,免疫荧光检测黏蛋白5AC(MUC5AC)的表达。基于UPLC-Q-TOF-MS筛选大麻二酚治疗肺纤维化的潜在生物标志物并进行通路富集分析。结果:与空白组比较,模型组大鼠肺组织出现大量炎性细胞浸润及连续纤维化病灶;与模型组比较,泼尼松组和大麻二酚组大鼠肺组织中炎性浸润减少,蓝色胶原沉积减少。与空白组比较,模型组血清中MMP-7、KL-6、SP-A、SP-D的表达量显著升高(P<0.01);与模型组比较,泼尼松组和大麻二酚高剂量组MMP-7、KL-6、SP-A、SP-D的表达量明显降低(P<0.05,P<0.01)。与空白组比较,模型组肺组织中Col-Ⅰ和FN的表达水平显著升高,MUC5AC的荧光强度显著增加(P<0.01);与模型组比较,泼尼松组和大麻二酚高剂量组肺组织中Col-Ⅰ和FN的表达水平明显降低(P<0.05,P<0.01),MUC5AC的表达显著下降(P<0.01)。模型组较空白组共筛选出18个差异化合物,可作为潜在生物标志物,大麻二酚可回调其中16个化合物,主要涉及亚油酸代谢,苯丙氨酸、酪氨酸和色氨酸生物合成,花生四烯酸代谢,烟酸和烟酰胺代谢4种代谢途径。与空白组比较,模型组潜在生物标志物花生四烯酸、亚油酸相对含量明显增加(P<0.05,P<0.01),5,6-EET、L-酪氨酸、烟酰胺相对含量显著降低(P<0.01);与模型组比较,大麻二酚能使花生四烯酸、亚油酸相对含量显著降低,5,6-EET、L-酪氨酸、烟酰胺相对含量均显著增加(P<0.01)。结论:大麻二酚对肺纤维化具有缓解作用,其作用机制可能与调节亚油酸代谢,苯丙氨酸、酪氨酸和色氨酸生物合成,花生四烯酸代谢,烟酸和烟酰胺代谢有关。

关键词：大麻二酚肺纤维化代谢组学炎症免疫超高效液相色谱-四极杆-飞行时间质谱法(UPLC-Q-TOF-MS)

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病原菌侵染下细胞外ATP对光系统Ⅱ光化学反应的调节作用

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兰州大学学报（自然科学版） 2024年第5期60卷 593-598页

作者：曹璐璐金昱杉张悦婧王涵琦邓雅欣孙坤张继贾凌云冯汉青西北师范大学生命科学学院兰州730070 西北师范大学中国商业联合会西北高原生物资源开发与生物制品重点实验室兰州730070

以野生型Col-0和细胞外ATP(e ATP)受体突变型dorn1-3拟南芥为实验材料,探究e ATP在两种丁香假单胞菌(毒性Pst DC3000和非毒性Pstavr B)侵染下的水平变化以及对其光化学反应的调节作用.结果表明,Pst DC3000和Pstavr B侵染均导致拟南芥叶... 详细信息

以野生型Col-0和细胞外ATP(e ATP)受体突变型dorn1-3拟南芥为实验材料,探究e ATP在两种丁香假单胞菌(毒性Pst DC3000和非毒性Pstavr B)侵染下的水平变化以及对其光化学反应的调节作用.结果表明,Pst DC3000和Pstavr B侵染均导致拟南芥叶片中e ATP水平、光适应下叶片的最大光化学量子产率(F_(v)′/F_(m)′)、光适应下PSⅡ实际光化学效率(Y(Ⅱ))、光合电子传递速率(ETR)降低而非调节性能量耗散的量子产额Y(NO)升高.Pst DC3000侵染下,dorn1-3拟南芥植株F_(v)′/F_(m)′、Y(Ⅱ)、ETR略低于野生型,Y(NO)略高于野生型,但均未达显著性差异;在Pstavr B侵染下,dorn1-3拟南芥植株F_(v)′/F_(m)′、Y(Ⅱ)、ETR显著低于野生型植株,Y(NO)显著高于野生型.在病原菌侵染下,e ATP受体的突变会增强病原菌对PSⅡ的抑制作用,且在非毒性病原菌侵染下该效应更为明显.在非毒性病原菌侵染对植物光化学反应影响的过程中e ATP具有重要的调控作用.

关键词：拟南芥丁香假单胞菌胞外ATP 叶绿素荧光参数

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