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A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 46-54页

作者： pin zhang Lin Wang Yueying Zhen Zhihong Wang Hesheng zhang Richard Jones Binghe Xu Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Tianjin Hemay Pharmaceutical Co. LTDTianjin 300308China

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer ***: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day *** samples were obtained on d 1 and d 28. Clinical responses were assessed every eight ***: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 ***: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).

关键词： Advanced breast cancer HER2-positive Hemay022 first-in-human trial

Synaptotagmins family affect glucose transport in retinal pigment epithelial cells through their ubiquitination-mediated degradation and glucose transporter-1 regulation

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World Journal of Diabetes 2024年第5期15卷 958-976页

作者： Hong Xu Li-Bo zhang Yi-Yi Luo Ling Wang Ye-pin zhang Pei-Qi Chen Xue-Ying Ba Jian Han Heng Luo Department of Ophthalmology The People’s Hospital of Chuxiong Yi Autonomous Prefecture&The Fourth Affiliated Hospital of Dali UniversityChuxiong Yi Autonomous Prefecture 675000Yunnan ProvinceChina Precision Medicine Center of Chuxiong Yi Autonomous Prefecture The People’s Hospital of Chuxiong Yi Autonomous Prefecture&The Fourth Affiliated Hospital of Dali UniversityChuxiong Yi Autonomous Prefecture 675000Yunnan ProvinceChina Department of Endocrinology The People’s Hospital of Chuxiong Yi Autonomous Prefecture&The Fourth Affiliated Hospital of Dali UniversityChuxiong Yi Autonomous Prefecture 675000Yunnan ProvinceChina Department of Pathology The People’s Hospital of Chuxiong Yi Autonomous Prefecture&The Fourth Affiliated Hospital of Dali UniversityChuxiong Yi Autonomous Prefecture 675000Yunnan ProvinceChina

BACKGROUND Synaptotagmins(SYTs)are a family of 17 membrane transporters that function as calcium ion sensors during the release of Ca2+-dependent neurotransmitters and ***,few studies have reported whether members of the SYT family play a role in glucose uptake in diabetic retinopathy(DR)through Ca2+/glucose transporter-1(GLUT1)and the possible regulatory mechanism of *** To elucidate the role of the SYT family in the regulation of glucose transport in retinal pigment epithelial cells and explore its potential as a therapeutic target for the clinical management of *** DR was induced by streptozotocin in C57BL/6J mice and by high glucose medium in human retinal pigment epithelial cells(ARPE-19).Bioinformatics analysis,reverse transcriptase-polymerase chain reaction,Western blot,flow cytometry,ELISA,HE staining,and TUNEL staining were used for *** Six differentially expressed proteins(SYT2,SYT3,SYT4,SYT7,SYT11,and SYT13)were found between the DR and control groups,and SYT4 was highly *** induces SYT4 overexpression,manipulates Ca2+influx to induce GLUT1 fusion with the plasma membrane,promotes abnormal expression of the glucose transporter GLUT1 and excessive glucose uptake,induces ARPE-19 cell apoptosis,and promotes DR *** deficiency inhibits the proteasomal degradation of SYT4 in DR,resulting in SYT4 accumulation and enhanced GLUT1 fusion with the plasma membrane,and these effects were blocked by oe-Parkin ***,dysregulation of the myelin transcription factor 1(Myt1)-induced transcription of SYT4 in DR further activated the SYT4-mediated stimulus-secretion coupling process,and this process was inhibited in the oe-MYT1-treated *** Our study reveals the key role of SYT4 in regulating glucose transport in retinal pigment epithelial cells during the pathogenesis of DR and the underlying mechanism and suggests potential therapeutic targets for clinical DR.

关键词： Diabetic retinopathy Glucose transporter-1 Synaptotagmin 4 Parkin Myelin transcription factor 1

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论城市社会学的学科规范与研究定位

中州学刊 2024年第8期 83-90页

作者：张品天津社会科学院中国特色社会主义理论体系研究中心天津300191

不同于社会学通过分析城市所承载的社会发展进程来把握社会秩序,城市社会学认为社会秩序至少部分地来自城市及其内部活动,因而以城市内部特定社会过程研究作为学科建立的依据,并将城市定义为承载社会运行的人口聚落,与之相应的研究对象... 详细信息

不同于社会学通过分析城市所承载的社会发展进程来把握社会秩序,城市社会学认为社会秩序至少部分地来自城市及其内部活动,因而以城市内部特定社会过程研究作为学科建立的依据,并将城市定义为承载社会运行的人口聚落,与之相应的研究对象便是与社会组织息息相关的资源分配过程。为了实现城市经验与秩序理论的融会贯通,城市社会学采用“理想类型普遍化”的研究方法,对塑造城市空间形态的具体区位性资源配置过程的特殊性进行概括。在“个人与社会的关系”这一社会学基本问题的限定下,个人以占有城市区位性资源的方式融入社会就构成了城市社会学的基本问题。学科规范决定了城市社会学的研究任务是揭示社会如何通过城市实现组织化,其作为社会学分支学科的研究定位也是以组织化视角来探讨社会秩序。从城市社会学的研究经验可以看出,社会学分支学科不是简单地运用社会学的理论与方法来分析某一社会现象或问题,而是立足社会学关注的社会秩序问题,从具体类型的人类实践中发现新的研究问题,据此建构自身知识体系。

关键词：城市社会学学科规范研究定位

Clinical benefit and safety profile of cross-line therapy with CDK4/6 inhibitors: a retrospective study of HR+/HER2–advanced breast cancer

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Cancer Biology & Medicine 2024年第10期 934-950页

作者： Qi Zhao Mingxia Jiang Jiaxuan Liu Mengqi zhang Maiyue He Shihan Zhou Jiani Wang Hongnan Mo Bo Lan Peng Yuan pin zhang Fei Ma Qiao Li Binghe Xu Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College

Objective: CDK4/6 inhibitors(CDK4/6is) in combination with endocrine therapy have secured a central role in the treatment of hormone receptor(HR)-positive advanced breast cancer(ABC) and have transformed the therapeutic landscape. Cross-line CDK4/6i therapy in which another CDK4/6i is continued after progression on a prior CDK4/6i may still offer advantageous therapeutic effects. Cross-line CDK4/6i therapy is an area of active investigation in the ongoing pursuit to improve outcomes for patients with HR+/human epidermal growth factor receptor 2(HER2)± ***: This retrospective study enrolled 82 patients with HR+/HER2± ABC who were treated with cross-line CDK4/6is(abemaciclib, palbociclib, ribociclib, and dalpiciclib) after progression with another CDK4/6i. The primary endpoint was progressionfree survival(PFS) according to version 1.1 of the Response Evaluation Criteria in Solid Tumors. Secondary endpoints included toxicity, objective response rate, disease control rate, and overall survival. Adverse events(AEs) were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events, as promulgated by the U.S. Department of Health and Human ***: Eighty-two HR+/HER2± ABC patients who received cross-line CDK4/6i therapy from January 2022 to February 2024 were enrolled. The median age of the patients was 60 years. The median PFS of all patients was 7.6 months(95% CI, 5.9-9.2). Cox regression analysis identified lung metastasis and a switch to endocrine therapy following prior CDK4/6i therapy as independent predictive factors for PFS. Notably, patients who previously received abemaciclib and switched to palbociclib upon disease progression had a median PFS of 10.7 months. The strategy of transitioning to chemotherapy after progression on a prior CDK4/6i, then to a subsequent CDK4/6i merits further investigation. Hematologic toxicity was the most common grade ≥ 3 AEs. No instances of fatal safety events were ***: Cro

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中国英语学习者词汇联想组织模式及网络结构的历时对比研究

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外语教学理论与实践 2024年第3期 10-18,9页

作者：张萍马宇晗苏州大学

本研究对比了两代(2005/2023)英语专业学生词汇联想网络的语义组织及整体网络变化。结果显示:1)两代学习者英语心理词库均以语义组织为主,高低水平者对词汇搭配和层级知识的侧重不同,现阶段学生的屈折派生知识显著提高;2)两代学习者的... 详细信息

本研究对比了两代(2005/2023)英语专业学生词汇联想网络的语义组织及整体网络变化。结果显示:1)两代学习者英语心理词库均以语义组织为主,高低水平者对词汇搭配和层级知识的侧重不同,现阶段学生的屈折派生知识显著提高;2)两代学习者的联想网络结构均符合“小世界”特性,网络疏密度随语言水平而增大至稳定,稳定性随小世界程度的加深而减弱。本研究为英语词汇学习提供了历时发展图景,对词汇学习诊断有启示。

关键词：词汇联想组织模式网络结构语义和网络分析历时对比

胃袖状切除术后病人发展为胃食管反流病的自然病程探讨

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中国实用外科杂志 2024年第8期44卷 863-867页

作者：张频张弘玮上海交通大学医学院附属第六人民医院减重代谢外科上海200233

胃食管反流病(GERD)在肥胖病人中高发,与体重变化密切相关。减重代谢手术可有效改善部分病人的GERD。然而,根据减重代谢手术的类型不同,也可能加重甚至引起新发的GERD。因此,对接受减重代谢手术,尤其是胃袖状切除术(SG)的病人而言,GERD... 详细信息

胃食管反流病(GERD)在肥胖病人中高发,与体重变化密切相关。减重代谢手术可有效改善部分病人的GERD。然而,根据减重代谢手术的类型不同,也可能加重甚至引起新发的GERD。因此,对接受减重代谢手术,尤其是胃袖状切除术(SG)的病人而言,GERD需重点关注。受影响病人不仅身体机能下降,还面临心理和情绪困扰,进而导致社交能力下降。SG术后GERD的发病是由解剖、生理和物理等多因素互相作用导致,包括袖状胃的形状、术中对食管括约肌的损伤程度以及是否合并食管裂孔疝。治疗方案则包括生活方式改变、药物、介入治疗和(或)修正手术等多种方式。

关键词：胃袖状切除术胃食管反流病肥胖抗反流屏障减重代谢手术

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采用动态相关度权重的特征选择算法

计算机工程与应用 2024年第4期60卷 89-98页

作者：许华杰刘冠霆张品秦远卓广西大学计算机与电子信息学院南宁530004 广西大学广西多媒体通信与网络技术重点实验室南宁530004 北部湾港防城港码头有限公司广西防城港538001 广西大学土木建筑工程学院南宁530004

基于互信息的特征选择算法在考虑候选特征提供的新分类信息时,通常忽略了候选特征的加入会使得已选特征和类标签的相关性发生变化而带来额外的新增信息量,以及在计算冗余信息时采用累加求和的形式可能导致低估候选特征的冗余程度。针对... 详细信息

基于互信息的特征选择算法在考虑候选特征提供的新分类信息时,通常忽略了候选特征的加入会使得已选特征和类标签的相关性发生变化而带来额外的新增信息量,以及在计算冗余信息时采用累加求和的形式可能导致低估候选特征的冗余程度。针对以上问题,提出动态相关度权重的定义,以更全面地考虑候选特征带来的新信息量成分;提出改进冗余项的定义,采用取最大值和归一化策略,以解决传统算法存在的低估冗余问题;在此基础上提出一种采用动态相关度权重的特征选择算法(feature selection using dynamic relevance weight,FSDRW)。选取五种当前主流的基于互信息的过滤式特征选择算法进行对比实验,在来自加州大学尔湾分校UCI和亚利桑那州立大学ASU的机器学习测试数据集上的实验表明,所提出的算法在分类准确率及综合性能方面具有较好的表现。最后将所提出算法应用于广西某水库工程的微震、爆破信号识别中,算法选取出的特征用于微震信号识别可达到98.86%的分类准确率,验证了算法在实际应用中的有效性。

关键词：特征选择互信息信息熵动态相关度权重

基于宿州某石料厂露天废弃矿山生态修复提升实践

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云南地质 2024年第1期43卷 128-133页

作者：张品楠安徽省地质环境监测总站(安徽省地质灾害应急技术指导中心) 安徽合肥230088

基于宿州市埇桥区符离镇某石料厂为例,2018年该矿山已通过治理验收,随着生态环境保护督察的开展,矿山暴露出一系列问题,针对矿山生态环境保护督察提出的问题,需进行生态环境成效提升,开展提升治理工作。本文分析了矿山存在的地质环境问... 详细信息

基于宿州市埇桥区符离镇某石料厂为例,2018年该矿山已通过治理验收,随着生态环境保护督察的开展,矿山暴露出一系列问题,针对矿山生态环境保护督察提出的问题,需进行生态环境成效提升,开展提升治理工作。本文分析了矿山存在的地质环境问题,提出了提升措施。

关键词：露天废弃矿山生态修复提升治理措施符离镇某石料厂安徽宿州

基于光纤光栅毛细钢管电镀封装结构的温度传感特性研究

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仪表技术与传感器 2024年第7期 25-29页

作者：刘明尧张品李聪武汉理工大学机电工程学院

采用毛细钢管对布拉格光纤光栅(FBG)封装有保护和温度增敏的效果。FBG和毛细钢管之间一般采用环氧胶连接,这会影响传感器的灵敏性和可靠性。为此,提出了一种基于磁控溅射和电镀相结合的毛细钢管封装工艺。首先在裸FBG上磁控溅射镍金属... 详细信息

采用毛细钢管对布拉格光纤光栅(FBG)封装有保护和温度增敏的效果。FBG和毛细钢管之间一般采用环氧胶连接,这会影响传感器的灵敏性和可靠性。为此,提出了一种基于磁控溅射和电镀相结合的毛细钢管封装工艺。首先在裸FBG上磁控溅射镍金属导电层,然后用电镀工艺将光纤和毛细钢管的两端固定连接。电镀连接层表面光滑,没有明显缺陷。相较于胶粘封装,使用电镀封装的FBG温度传感器在25~95℃的温度范围内具有优异的线性度。封装结构的温度传感灵敏度是裸FBG的2.63倍。结果表明,毛细钢管电镀封装结构不仅可以提高温度传感灵敏度,还能在高温下具有稳定的传感性能。

关键词：布拉格光纤光栅温度传感器毛细管磁控溅射电镀封装结构