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Sustained co-delivery of 5-fluorouracil and cis-platinum via biodegradable thermo-sensitive hydrogel for intraoperative synergistic combination chemotherapy of gastric cancer

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Bioactive Materials 2023年第5期23卷 1-15页

作者： Wen Chen Kun Shi Jie Liu Peipei Yang Ruxia Han Meng Pan Liping yuan Chao Fang yongyang yu Zhiyong Qian State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan University and Collaborative Innovation CenterChengdu610041PR China Department of Gastrointestinal Surgery West China HospitalSichuan UniversityChengdu610041PR China

Gastric cancer is the fifth most common cancer and the third leading cause of cancer death worldwide,posing a severe threat to human health.Surgical resection remains the most preferred option for gastric cancer treatment.However,for advanced gastric cancer,the curative effect of surgical resection is usually limited by the local recurrence,peritoneal carcinomatosis,or distal metastasis.Intraoperative chemotherapy is an attractive in situ adjuvant treatment strategy to reduce the recurrence and metastasis after surgical resection.Here,we designed a 5-fluorouracil(5-FU)and cis-platinum(DDP)co-delivery system based on a biodegradable temperature-sensitive hydrogel(PDLLA-PEG-PDLLA,PLEL)for intraoperative adjuvant combination chemotherapy of gastric cancer.This 5-FU+DDP/PLEL hydrogel system characterized by a special sol-gel phase transition in response to physiological temperature and presented sustained drug release in vitro and in vivo.A strong synergistic cell proliferation inhibition and apoptosis promotion of 5-FU+DDP/PLEL were observed against gastric cancer MKN45-luc cells.After intraperitoneal injection,the dual-drug loaded hydrogel formulation showed superior anti-tumor effects than the single-drug carrying hydrogels and combination of free 5-FU and DDP on the gastric cancer peritoneal carcinomatosis model.The use of hydrogel for dual-drug delivery had benefited to fewer side effects as well.What’s more,we established a mouse model for postsurgical residual tumors and peritoneal carcinomatosis of gastric cancer,in which the intraoperative administration of 5-FU+DDP/PLEL also remarkably inhibited the local recurrence of the orthotopic tumors and the growth of the abdominal metastatic tumors,resulting in an extended lifetime.Hence,this developed dual-drug loaded hydrogel system has great potential in the intraoperative chemotherapy of gastric cancer,that suggests a clinically-relevant and valuable option for postsurgical management of gastric cancer.

关键词： Thermo-sensitive hydrogel Localized drug delivery Sustained release Intraoperative chemotherapy Gastric cancer

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Cyclophosphamide loaded thermo-responsive hydrogel system synergize with a hydrogel cancer vaccine to amplify cancer immunotherapy in a prime-boost manner

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Bioactive Materials 2021年第10期6卷 3036-3048页

作者： Fan Yang Kun Shi Ying Hao Yanpeng Jia Qingya Liu yu Chen Meng Pan Liping yuan yongyang yu Zhiyong Qian State Key Laboratory of Biotherapy and Cancer Center Collaborative Innovation Center for BiotherapyWest China HospitalSichuan UniversityChengdu610041PR China Department of Gastrointestinal Surgery West China HospitalSichuan UniversityChengdu610041PR China

Although neoantigen-based cancer vaccines show great potential in cancer immunotherapy due to their ability to induce effective and long-lasting anti-tumor immunity,their development is hindered by the limitations of neoantigens identification,low immunogenicity,and weak immune response.Cyclophosphamide(CTX)not only directly kills tumors but also causes immunogenic cell death,providing a promising source of antigens for cancer vaccines.Herein,a combined immunotherapy strategy based on temperature-sensitive PLEL hydrogel is designed.First,CTX-loaded hydrogel is injected intratumorally into CT26 bearing mice to prime anti-tumor immunity,and then 3 days later,PLEL hydrogels loaded with CpG and tumor lysates are subcutaneously injected into both groins to further promote anti-tumor immune responses.The results confirm that this combined strategy reduces the toxicity of CTX,and produces the cytotoxic T lymphocyte response to effectively inhibit tumor growth,prolong survival,and significantly improve the tumor cure rate.Moreover,a long-lasting immune memory response is observed in the mice.About 90%of the cured mice survive for at least 60 days after being re-inoculated with tumors,and the distant tumor growth is also well inhibited.Hence,this PLEL-based combination therapy may provide a promising reference for the clinical promotion of chemotherapy combined with cancer vaccines.

关键词： Immunotherapy Thermo-responsive hydrogels Immunogenic cell death Cancer vaccine Cyclophosphamide

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浙江省《民用建筑项目节能评估技术规程》中碳排放计算方法解读

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浙江建筑 2024年第2期41卷 12-16页

作者：牟宇林敏敏李甬扬宁太刚陈泓蓓浙江大学建筑设计研究院有限公司浙江杭州310027 浙江省建设工程造价管理总站浙江杭州310012

详细介绍了《民用建筑项目节能评估技术规程(DBJ33/T1288—2022)》中碳排放计算方法,细致解读了对建筑碳排放计算边界、碳排放因子取值。将建筑能耗归为动态能耗计算和静态能耗计算两种计算方法,并针对各用能系统进行了深入剖析。创新... 详细信息

详细介绍了《民用建筑项目节能评估技术规程(DBJ33/T1288—2022)》中碳排放计算方法,细致解读了对建筑碳排放计算边界、碳排放因子取值。将建筑能耗归为动态能耗计算和静态能耗计算两种计算方法,并针对各用能系统进行了深入剖析。创新性地提出了建筑运行碳排放降幅的概念和计算公式,为规范浙江省建筑碳排放计算方法和量化建筑降碳数据提供了有力保障。

关键词：建筑运行碳排放运行碳排放降幅基准建筑

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丙硫菌唑和氟唑菌酰羟胺复配对小麦赤霉病菌的联合毒力

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浙江农业科学 2024年第3期65卷 667-671页

作者：祁月月邵宇张平胡宗林钮建国冯星凯胡永阳浙江天丰生物科学有限公司浙江金华321000

为探明丙硫菌唑、氟唑菌酰羟胺对禾谷镰刀菌引起的小麦赤霉病的联合毒力。本研究采用菌丝生长速率法,测定丙硫唑菌和氟唑菌酰羟胺对禾谷镰刀菌的室内生物活性,确定丙硫菌唑和氟唑菌酰羟胺防治小麦赤霉病的最佳复配比例。结果表明,丙硫... 详细信息

为探明丙硫菌唑、氟唑菌酰羟胺对禾谷镰刀菌引起的小麦赤霉病的联合毒力。本研究采用菌丝生长速率法,测定丙硫唑菌和氟唑菌酰羟胺对禾谷镰刀菌的室内生物活性,确定丙硫菌唑和氟唑菌酰羟胺防治小麦赤霉病的最佳复配比例。结果表明,丙硫菌唑、氟唑菌酰羟胺对小麦赤霉病菌的EC_(50)分别为22.44、0.33 mg·L^(-1)。在丙硫菌唑和氟唑菌酰羟胺的3个不同配比中,2∶3配比时EC_(50)最小,为0.19 mg·L^(-1);1∶1配比时EC_(50)值最大,为0.47 mg·L^(-1)。丙硫菌唑和氟唑菌酰羟胺质量比为1∶1、2∶3和1∶2的共毒系数分别为137.54、285.91、175.36。综合增效作用考虑,丙硫菌唑和氟唑菌酰羟胺以2∶3混配效果最佳。结果表明,50%丙硫菌唑·氟唑菌酰羟胺悬浮剂300、400、500 mL·hm^(-2)施药25 d对小麦赤霉病的防治效果分别为91.76%、97.03%、99.77%,防治效果突出。50%丙硫菌唑·氟唑菌酰羟胺悬浮剂可以防治小麦赤霉病,在小麦赤霉病发生初期使用,施药2次,2次施药间隔10~15 d。

关键词：丙硫菌唑氟唑菌酰羟胺小麦赤霉病联合毒力测定田间药效

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Interacting effects of multiple factors on the morphological evolution of the meandering reaches downstream the Three Gorges Dam

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Journal of Geographical Sciences 2017年第10期27卷 1268-1278页

作者： HAN Jianqiao ZHANG Wei FAN yongyang yu Mengqing Institute of Soil and Water Conservation Northwest A&F University Yangling 712100 Shaanxi China State Key Laboratory of Water Resources and Hydropower Engineering Science Wuhan University Wuhan 430072 China Changjiang Institute of Survey Planning Design and Research Wuhan 430010 China

Elucidating the influence of dams on fluvial processes can inform river protection and basin management. However, relatively few studies have focused on how multiple factors interact to affect the morphological evolution of meandering reaches. Using hydrological and topographical data, we analyzed the factors that influence and regulate the meandering reaches downstream the Three Gorges Dam （TGD）. Our conclusions are as follows. （1） The meandering reaches can be classified into two types based on their evolution during the pre-dam period： G1 reaches, characterized by convex point bar erosion and concave channel deposition （CECD）, and G2 reaches, characterized by convex point bar deposition and concave channel erosion （CDCE）. Both reach types exhibited CECD features during the post-dam period, （2） Flow processes and sediment transport are the factors that caused serious erosion of the low beaches located in the convex point bars. However, changes in the river regime, river boundaries and jacking of Dongting Lake do not act as primary controls on the morphological evolution of the meandering reaches. （3） Flood discharges ranging from 20,000 to 25,000 m^3/s result in greater erosion of convex point bars. The point bars become scoured if the durations of these flows, which are close to bankfull discharge, exceed 20 days. In addition, the reduction in bedload causes the decreasing of point bar siltation in the water-falling period. （4） During the post-dam period, flood abatement, the increased duration of discharges ranging from 20,000 to 25,000 m^3/s, and a significant reduction in sediment transport are the main factors that caused meandering reaches to show CECD features. Our results are relevant to other meandering reaches, where they can inform estimates of riverbed change, river management strategies and river protection.

关键词： reaches downstream dams meandering river morphological evolution Three Gorges Dam

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Mutations in TP53, ZNF750, and RB1 typify ocular sebaceous carcinoma

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Journal of Genetics and Genomics 2019年第6期46卷 315-318页

作者： yongyang Bao J. Eva Selfridge Janet Wang Yiqing Zhao Junqi Cui Kishore Guda Zhenghe Wang Yanbo Zhu Department of Pathology The Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200011 China Seidman Cancer Center University Hospitals Cleveland Medical Center Cleveland OH 44106 USA Case Comprehensive Cancer Center Cleveland OH 44106 USA Department of Genetics and Genome Sciences Case Western Reserve University Cleveland OH 44106 USA

Sebaceous carcinoma (SC) of the eyelid is a rare but aggressive malignancy, accounting for 3%—5% of eyelid malignancies in the United States, and up to 35% in Asian populations (Deprez and Uffer, 2009;Xu et al., 2018;yu et al., 2018). It is frequently mistaken for benign conditions or less aggressive malignancies such as basal cell carcinoma (Muqit et al., 2013), and the effects of delay in diagnosis can be devastating to patients. Aggressive surgical resection is the primary treatment of these tumors and often invoIves orbital exenteration with significant morbidity to patients, and these tumors frequently recur, with local recurrence rate as high as 18%. Importantly, this disease has a high metastatic potential, and there are very limited data guiding systemic treatment options;ultimately 6%—18% of patients diagnosed with SC of the eyelid succumb to metastatic disease (Zurcher et al., 1998;Shields et al., 2004).

关键词： Sebaceous carcinoma (SC) RB1 TP53 ZNF750

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Design and performance assessment of a time-varying channel simulator for high-mobility satellite navigation scenarios

Design and performance assessment of a time-varying channel ...

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第十四届中国卫星导航年会

作者： Shun Zhou Shiyun yu Wei Shi yongyang Hu The Sixty-Third Research Institute National University of Defense Technology

With the development of high-mobility satellite navigation systems such as LEO satellite navigation enhancement system,the ability of traditional fixed channel models to simulate channel characteristics has been widely challenged.This work focuses on the background theory,time-varying emulator design,and performance assessment application for the necessity of a channel simulator to enable the propagation modeling from LEO satellite to mobile receiver in the high-mobility satellite navigation scenario.The concept of satellite Doppler effect,separation of satellite Doppler shift,and local Doppler shift are discussed in this work,along with the sampling criteria for time-varying channel modeling.The time-varying simulator based on the model of the time-varying satellite navigation channel is provided,and it is used to assess the tracking loop performance of the navigation software receiver.The results show that the rapidly updating time-varying channel will subject the receiver to severe fluctuations and may possibly result in the tracking loop losing lock.In general,the rapidly timevarying channel scenario is more challenging to track and produce stable output than the general multipath channel scenario.

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关于我国新时代大学声誉保护的内涵、生成与路径探究

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化工高等教育 2022年第1期39卷 148-155页

作者：于泳洋赵越南京大学政府管理学院江苏南京210093 南京大学党委办公室江苏南京210093 南京大学南京大学医学院江苏南京210046

大学声誉保护研究是我国新时代高等教育事业发展中一个值得深入思考的问题,它既是高等教育改革的题中之义,也是政治形态转型的关键环节,更是应急管理的重要组成。但从目前的现实看,围绕大学声誉保护的相关研究较为缺乏。文章理清了大学... 详细信息

大学声誉保护研究是我国新时代高等教育事业发展中一个值得深入思考的问题,它既是高等教育改革的题中之义,也是政治形态转型的关键环节,更是应急管理的重要组成。但从目前的现实看,围绕大学声誉保护的相关研究较为缺乏。文章理清了大学声誉保护的概念、生成、现实基础及价值取向,进而探究了其实质和内涵,并为大学声誉保护提供了可能的途径和改革举措。

关键词：大学声誉保护高等教育政治形态应急管理

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面向频谱接入深度强化学习模型的后门攻击方法

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计算机科学 2023年第1期50卷 351-361页

作者：魏楠魏祥麟范建华薛羽胡永扬南京信息工程大学计算机与软件学院南京210044 国防科技大学第六十三研究所南京210007

深度强化学习(Deep Reinforcement Learning,DRL)方法以其在智能体感知和决策方面的优势,在多用户智能动态频谱接入问题上得到广泛关注。然而,深度神经网络的弱可解释性使得DRL模型容易受到后门攻击威胁。针对认知无线网络下基于深度强... 详细信息

深度强化学习(Deep Reinforcement Learning,DRL)方法以其在智能体感知和决策方面的优势,在多用户智能动态频谱接入问题上得到广泛关注。然而,深度神经网络的弱可解释性使得DRL模型容易受到后门攻击威胁。针对认知无线网络下基于深度强化学习模型的动态频谱接入(Dynamic Spectrum Access,DSA)场景,提出了一种非侵入、开销低的后门攻击方法。攻击者通过监听信道使用情况来选择非侵入的后门触发器,随后将后门样本添加到次用户的DRL模型训练池,并在训练阶段将后门植入DRL模型中;在推理阶段,攻击者主动发送信号激活模型中的触发器,使次用户做出目标动作,降低次用户的信道接入成功率。仿真结果表明,所提后门攻击方法能够在不同规模的DSA场景下达到90%以上的攻击成功率,相比持续攻击可以减少20%~30%的攻击开销,并适用于3种不同类型的DRL模型。

关键词：动态频谱接入深度强化学习后门攻击触发器

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基于实验思想的技术与战法协同演进研究——以我国抗击高空侦察机U-2为案例

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自然辩证法通讯 2020年第5期42卷 100-108页

作者：余永阳王大洲中国科学院大学人文学院北京100049 国防大学军事管理学院北京100091

采用案例研究方法,以上世纪50年代末至70年代初我国抗击高空侦察机历程为对象,从实验的角度,聚焦军事能力生成与释放的关键要素,剖析技术与战法的协同进化及作战能力螺旋式上升的辩证过程。表明:军事技术不能自动带来"红利",需集成至整... 详细信息

采用案例研究方法,以上世纪50年代末至70年代初我国抗击高空侦察机历程为对象,从实验的角度,聚焦军事能力生成与释放的关键要素,剖析技术与战法的协同进化及作战能力螺旋式上升的辩证过程。表明:军事技术不能自动带来"红利",需集成至整个作战体系并融合于战法之中方能发挥其应有的效力;这实际上是技术、战法和作战能力的协同进化过程,而要完成这个过程,实验在其中发挥着关键的"工具"性价值和基础性作用。本项研究有助于深化关于工程实验的哲学研究。

关键词：实验技术战法军事实验工程实验

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