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Improving the prognosis of pancreatic cancer:insights from epidemiology,genomic alterations,and therapeutic challenges

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Frontiers of Medicine 2023年第6期17卷 1135-1169页

作者： Zhichen Jiang xiaohao zheng Min Li Mingyang Liu State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of General Surgery Division of Gastroenterology and PancreasZhejiang Provincial People's HospitalAffiliated People's HospitalHangzhou Medical CollegeHangzhou 310014China Department of Pancreatic and Gastric Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of General Surgery Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Medicine The University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA

Pancreatic cancer,notorious for its late diagnosis and aggressive progression,poses a substantial challenge owing to scarce treatment alternatives.This review endeavors to furnish a holistic insight into pancreatic cancer,encompassing its epidemiology,genomic characterization,risk factors,diagnosis,therapeutic strategies,and treatment resistance mechanisms.We delve into identifying risk factors,including genetic predisposition and environmental exposures,and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer.Additionally,we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy.We also dissect the primary mechanisms underlying treatment resistance in this malignancy,illustrating the latest therapeutic options and advancements in the field.Conclusively,we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.

关键词： pancreatic cancer cancer screening single cell molecular alterations precancerous lesion therapy resistance

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面向深度学习模型的可靠性测试综述

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信息安全学报 2024年第1期9卷 33-55页

作者：陈若曦金海波陈晋音郑海斌李晓豪浙江工业大学信息工程学院杭州310023 浙江工业大学网络空间安全研究院杭州310023

深度学习模型由于其出色的性能表现而在各个领域被广泛应用,但它们在面对不确定输入时,往往会出现意料之外的错误行为,在诸如自动驾驶系统等安全关键应用,可能会造成灾难性的后果。深度模型的可靠性问题引起了学术界和工业界的广泛关注... 详细信息

深度学习模型由于其出色的性能表现而在各个领域被广泛应用,但它们在面对不确定输入时,往往会出现意料之外的错误行为,在诸如自动驾驶系统等安全关键应用,可能会造成灾难性的后果。深度模型的可靠性问题引起了学术界和工业界的广泛关注。因此,在深度模型部署前迫切需要对模型进行系统性测试,通过生成测试样本,并由模型的输出得到测试报告,以评估模型的可靠性,提前发现潜在缺陷。一大批学者分别从不同测试目标出发,对模型进行测试,并且提出了一系列测试方法。目前对测试方法的综述工作只关注到模型的安全性,而忽略了其他测试目标,且缺少对最新出版的方法的介绍。因此,本文拟对模型任务性能、安全性、公平性和隐私性4个方面对现有测试技术展开全方位综述,对其进行全面梳理、分析和总结。具体而言,首先介绍了深度模型测试的相关概念;其次根据不同测试目标对79篇论文中的测试方法和指标进行分类介绍;然后总结了目前深度模型可靠性测试在自动驾驶、语音识别和自然语言处理三个工业场景的应用,并提供了可用于深度模型测试的24个数据集、7个在线模型库和常用工具包;最后结合面临的挑战和机遇,对深度模型可靠性测试的未来研究方向进行总结和展望,为构建系统、高效、可信的深度模型测试研究提供参考。值得一提的是,本文将涉及的数据集、模型、测试方法代码、评价指标等资料归纳整理在https://***/Allen-piexl/Testing-Zoo,方便研究人员下载使用。

关键词：深度学习模型深度测试可靠性安全性公平性隐私性

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Bioinspired MXene-Based User-Interactive Electronic Skin for Digital and Visual Dual-Channel Sensing

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Nano-Micro Letters 2022年第7期14卷 228-245页

作者： Wentao Cao zheng Wang xiaohao Liu Zhi Zhou Yue Zhang Shisheng He Daxiang Cui Feng Chen Department of Orthopedic School of MedicineSpinal Pain Research InstituteShanghai Tenth People’s HospitalTongji UniversityShanghai 200072People’s Republic of China National Engineering Research Center for Nanotechnology Shanghai 200241People’s Republic of China Institute of Micro-Nano Science and Technology School of Electronic Information and Electrical EngineeringShanghai Jiao Tong UniversityShanghai 200240People’s Republic of China

User-interactive electronic skin(e-skin) that could convert mechanical stimuli into distinguishable outputs displays tremendous potential for wearable devices and health care applications. However, the existing devices have the disadvantages such as complex integration procedure and lack of the intuitive signal display function. Here, we present a bioinspired user-interactive e-skin, which is simple in structure and can synchronously achieve digital electrical response and optical visualization upon external mechanical stimulus. The e-skin comprises a conductive layer with a carbon nanotubes/cellulose nanofibers/MXene nanohybrid network featuring remarkable electromechanical behaviors, and a stretchable elastomer layer, which is composed of silicone rubber and thermochromic pigments. Furthermore, the conductive nanohybrid network with outstanding Joule heating performance can generate controllable thermal energy under voltage input and then achieve the dynamic coloration of silicone-based elastomer. Especially, such an innovative fusion strategy of digital data and visual images enables the e-skin to monitor human activities with evermore intuition and accuracy. The simple design philosophy and reliable operation of the demonstrated e-skin are expected to provide an ideal platform for next-generation flexible electronics.

关键词： MXene Electronic skin Electromechanical behavior Joule heating Visualization

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1例FGA基因c.2185G>A变异所致遗传性异常纤维蛋白原血症并发深静脉血栓的分析

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临床检验杂志 2024年第2期42卷 117-120页

作者：潘晓浩何卫黄建芳郑晓勇温州市中西医结合医院检验科浙江温州325001 温州医科大学附属第一医院医学检验中心浙江温州325015

目的对1例遗传性异常纤维蛋白原血症(CD)患者出现深静脉血栓形成(DVT)进行分析,探讨CD与DVT的关系。方法临床资料收集及家系调查(共2代3人)。检测患者及其家系成员相关凝血指标。提取外周血基因组DNA进行PCR扩增,采用DNA直接测序法分析... 详细信息

目的对1例遗传性异常纤维蛋白原血症(CD)患者出现深静脉血栓形成(DVT)进行分析,探讨CD与DVT的关系。方法临床资料收集及家系调查(共2代3人)。检测患者及其家系成员相关凝血指标。提取外周血基因组DNA进行PCR扩增,采用DNA直接测序法分析患者纤维蛋白原(Fg)的FGA、FGB和FGG基因所有外显子、侧翼序列、5′和3′端非翻译区序列,及家系成员相应的变异位点区域。用PyMol软件构建基因变异前后蛋白模型。结果患者为行子宫肌瘤切除术入院,术后3天出现DVT。术前凝血指标检查显示患者的凝血酶原时间(PT)、凝血酶时间(TT)、Fg活性(Fg:C)和Fg抗原(Fg:Ag)分别为14.9 s、33.3 s、0.94 g/L和2.10 g/L;其母亲上述4项指标分别为14.7 s、32.8 s、0.97 g/L和2.35 g/L。DNA测序发现患者及其母亲的FGA基因第6号外显子均存在c.2185G>A杂合错义变异(p.Glu729Lys)。蛋白模型分析显示,p.Glu729Lys变异使Fg结构发生了改变。结论该先证者FGA基因第6号外显子c.2185G>A(NM_000508)杂合错义变异与其Fg:C减低有关,可能也是该患者出现DVT的原因之一。

关键词：遗传性异常纤维蛋白原血症基因变异深静脉血栓形成

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Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice

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International Journal of Oral Science 2022年第3期14卷 371-380页

作者： Yumei Lai Wei zheng Minghao Qu Christopher C.Xiao Sheng Chen Qing Yao Weiyuan Gong Chu Tao Qinnan Yan Peijun Zhang xiaohao Wu Guozhi Xiao Department of Orthopedic Surgery Rush University Medical CenterChicagoILUSA Department of Orthopaedic Center Xinjiang Production and Construction Corps HospitalUrumqiChina Department of Biochemistry School of MedicineSouthern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentShenzhenChina Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint(TMJ) osteoarthritis(OA);however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4(Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore,Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.

关键词： Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice TMJ

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Identification of a major quantitative trait locus and its candidate underlying genetic variation for rice stigma exsertion rate

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The Crop Journal 2019年第3期7卷 350-359页

作者： Shouling Xu Yunchao zheng Yang Liu xiaohao Guo Yuanyuan Tan Qiuping Qian Qingyao Shu Jianzhong Huang National Key Laboratory of Rice Biology Institute of Nuclear Agricultural SciencesZhejiang UniversityHangzhou 310058ZhejiangChina Hubei Collaborative Innovation Center for Grain Industry Jingzhou 434025HubeiChina Institute of Crop Sciences Zhejiang UniversityHangzhou 310058ZhejiangChina Jinhua Academy of Agricultural Sciences Jinhua 321017ZhejiangChina

Stigma exsertion in male sterile lines of hybrid rice is important for seed yield.In the present study, ZS616 [Oryza sativa subsp.Xian(indica)], a male sterile line with a stigma exsertion rate(SER) as high as 94.5%, was crossed to DS552, a japonica line with almost no exserted stigmas.F3 plants with extremely low and high SER were sequenced to identify SER-associated quantitative trait loci(QTL).A major QTL for SER, qSER-3.1, was identified along with other QTL on chromosome 3 in a 3.9 Mb region.A total of 307 nonsynonymous single-nucleotide polymorphisms(SNPs) and 27 frame-shift insertion/deletions(InDels)differentiating ZS616 and DS552 were identified in the region containing qSER-3.1.Most SNPs(294) and InDels(25) were excluded after further analysis because they were shared by ZS616 and low(<2.0%) SER accessions in the Huazhong Agricultural University(HAU) core rice collection.Association analysis using the full HAU collection identified a 17-bp InDel in OS03 G0689400 as the most likely causal genetic variant underlying qSER-3.1.ZS616-type accessions(n = 54, with the 17-bp insertion) in the HAU collection had minimum(16.5%)and mean(39.6%) SERs significantly greater than those(n = 424) without the insertion(with minimum and mean SERs of 0.2% and 20.6%, respectively).Thus, this study identified a major QTL for stigma exsertion and revealed the mutation in a candidate gene for the QTL.

关键词： Hybrid rice Stigma exsertion Seed production QTL-seq qSER-3.1 GS3

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Sedimentary characteristics of paleo-aeolian dune sands of Salawusu Formation in the Salawusu River Valley

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Journal of Geographical Sciences 2008年第2期18卷 211-224页

作者： OU Xianjiao LI Baosheng JIN Heling DONG Guangrong David Dian ZHANG WU zheng WEN xiaohao ZENG Lanhua OUYANG Chuntao YANG Yi LIU Yufei School of Geography South China Normal University Guangzhou 510631 China State Key Laboratory of Loess and Quaternary Geology Institute of Earth Environment CAS Xi＇an 710061 China Department of Geography Jiaying University Meizhou 514015 China Cold and Arid Regions Environmental and Engineering Research Institute CAS Lanzhou 730000 China Department of Geography and Geology the University of Hong Kong Hong Kong China

The Salawusu Formation of Milanggouwan section in Salawusu River Valley includes 7 layers of paleo-mobile dune sands, and 4 layers of paleo-fixed and semi-fixed dune sands. Their structures have been observed and their grain size, surface textural features and several main chemical elements have been analyzed. The results showed that： 1） Some of the aeolian structural characteristics of these dune sands are similar to that of the recent dune sands. 2） They are also similar to the recent dune sands in grain size components, and parameters of Mz,σ, Sk and Kg, as well as in several main chemical components. 3） The scattergrams of Mz-σ and SiO2-Al2O3＋TOFE and the probability curves of grain size showed that these paleo-dune sands are different from paleosols and fluvio-lacustrine facies, but are consistency with recent dune sands. 4） Quartz sands have well roundness and surface textural features such as dish-shaped pits, crescent-shaped pits, pockmarked pits, upturned cleavage plates, siliceous precipitates and siliceous crevasses, indicating that they had been carried for a long time by the wind. As the 11 layers of paleo-dune sands possess the aeolian characteristics in structure, grain size, surface textural features and chemical elements, the origin of their formation should be attributed to eolation.

关键词： Salawusu River Valley Salawusu Formation paleo-aeolian dune sands aeolian sedimentary characteristics

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湖北省生态系统服务价值动态变化及其影响因素演变

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生态环境学报 2023年第1期32卷 195-206页

作者：郑晓豪陈颖彪郑子豪郭城黄卓男周泳诗广州大学地理科学与遥感学院/广东省地理国情监测与综合分析工程技术研究中心广东广州510006

把握生态系统服务价值(ESV)动态变化特征,厘清其主导因素的演变趋势,对于区域生态建设意义重大。基于2005、2010、2015和2019年的遥感解译数据,结合当量因子法和空间统计工具,分析了湖北省ESV的动态变化特征,利用随机森林模型识别ESV的... 详细信息

把握生态系统服务价值(ESV)动态变化特征,厘清其主导因素的演变趋势,对于区域生态建设意义重大。基于2005、2010、2015和2019年的遥感解译数据,结合当量因子法和空间统计工具,分析了湖北省ESV的动态变化特征,利用随机森林模型识别ESV的主导因素,并运用时空地理加权回归(GTWR)模型对其主导因素的驱动作用进行探究。结果显示,(1)2005—2019年湖北省ESV整体减少124.31×10^(8)元,但是下降率由2005—2010年的1.14%缩减至2015—2019年的0.57%。历年ESV呈现“四周高中间低”的分布特征,研究期间有83.4%区域的ESV处于上下轻微波动的状态,空间分布较为稳定。(2)随机森林排序结果显示,社会经济因素对ESV的重要程度更高,自然因素次之。重要性排名前六位的分别是人类活动(60.16%)、净初级生产力(50.66%)、年降雨量(46.85%)、地区生产总值密度(34.00%)、人口密度(29.53%)和建设用地占比(29.36%),地形因素及年均温度排名相对较低。ESV主导因素重要性变化结果表明,研究时段内,除人类活动和降水等因素的重要性呈现下降趋势外,其他因素的重要性均有不同程度的上升。(3)不同区域ESV主导因素的作用强度和波动方向各不相同。其中,人类活动对ESV的驱动作用最强,呈现全局负相关,在鄂西最为明显;净初级生产力的正向影响区域主要集中在恩施州东部、宜昌市西部以及十堰市西部;年降雨量的负向影响在江汉平原逐渐稳定;人口密度和GDP密度在三峡和丹江口库区的波动方向于2010年后呈相背离趋势;建设用地占比的波动方向呈现明显的西正东负。研究结果可为湖北省制定针对性的生态保护政策提供参考,同时为生态与经济协调可持续发展提供理论依据。

关键词：生态系统服务价值时空演变随机森林模型影响因素时空地理加权回归模型

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Deposition of sandstorms in a vegetation-covered sand dune in Ejin Oasis and its characteristics

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Journal of Geographical Sciences 2006年第4期16卷 502-508页

作者： WENxiaohao LI Baosheng WANG Wei LI Sen OU Xianjiao zheng Yanming Sehool of Geography South China Normal University Guangzhou 510631 China State Key Laboratory of Loess and Quaternary Geology Institute of Earth Environment CAS Xi＇an 710075 China Department of Tourism Resourees and Environment Foshan University Foshan 528000 China

＂Ejin Section＂ found in a typical vegetation-covered sand dune in Ejin Oasis was investigated. In this study, 263 samples were taken from the section for grain-size analysis, 25 for chemical analysis, 11 for ^14C dating and 6 for scanning electron microscope （SEM）. The results of the study indicate that 3 types of the sediments in the section can be identified, YS, LS and ST. YS, homogeneous yellow-brown dune sands, is equal to those of inland deserts, LS, loess-like sandy soils, is the same as the sandy loess in the middle Yellow River and modem falling dusts, and ST, sandy sediments interbeded with the deadwood and defoliation of Tamarix spp, represents the depositional process of the section interrupted by abrupt changes in climate. The Ejin Section has recorded the repeated dust-storms or sandstorms since 2500 yr BP and the peak periods of the dust-storms or sandstorms revealed by the section are consistent with the records of ＂dust rains＂ in historical literatures, indicating that the change of climate is a key factor to increase sandstorms or dust-storms, whereas, ＂artificial＂ factor may only be an accelerating one for desertification.

关键词： Ejin Oasis vegetation-covered sand dune dust storm sandstorm grain size major chemical element

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Grain-size Characteristics and Climate Variability in TMS5e Sequence of Tumen Section in Southern Tengger Desert,Northwestern China

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Chinese Geographical Science 2012年第1期22卷 48-62页

作者： WEN xiaohao LI Baosheng WANG Fengnian zheng Yanming NIU Dongfeng SI Yuejin OU Xianjiao School of Geographical Science South China Normal University Guangzhou 510631 China State Key Laboratory of Loess and Quaternary Geology Institute of Earth Environment Chinese Academy of Sciences Xi＇an 710075 China School of Geography and Planning Sun Yat-Sen University Guangzhou 510275 China School of Geography and Tourism Jiaying University Meizhou 514015 China

The TMS5e sequence from the Tumen section,at the southern edge of Tengger Desert in the northwestern China,is synchronous with Marine Isotope Stage 5e(MIS5e).It consists of 16 layers of aeolian dune sands,11 layers of lacustrine loess-like facies,and 5 layers of lacustrine facies.The results of grain-size analysis shows that the palaeo-mobile dune sands,palaeo-fixed to semi-fixed dune sands and loess-like sandy loams are mainly composed of sands,ranging from 70% to 96%;their silt contents ranged from 4% to 20%,and their clay contents ranged from 1% to 5%;the climate under which the aeolian dune sands were deposited is similar to that under which modern mobile dune sands form,which is caused by the dominance of the cold,dry East Asian winter monsoon.In contrast,the lacustrine loess-like facies and lacustrine facies had a lower sand contents than those of the three aeolian dune sands,but have higher silt and clay contents,most of their sand content ranged from 30% to 60%,their silt contents ranged from 35% to 55%,and their clay contents ranged from 6% to 20%.The lacustrine loess-like facies and lacustrine facies formed under the influence of the warm,humid East Asian summer monsoon based on their similarity with modern sediments.The grain-size indicator Mz(mean grain diameter) and the SC/D value in the TMS5e sequence indicate climatic insta-bility at the southern edge of the Tengger Desert during MIS5e,with at least 14 fluctuations between a warm,humid climate and a cold,dry climate,divided into five stages:TMS5e5(139 kyr to 129.3 kyr B.P.),TMS5e4(129.3 kyr to 124 kyr B.P.),TMS5e3(124 kyr to 119.5 kyr B.P.),TMS5e2(119.5 kyr to 116.5 kyr B.P.),and TMS5e1(116.5 kyr to 113.7 kyr B.P.).These correspond roughly to MIS5e5,MIS5e4,MIS5e3,MIS5e2,and MIS5e1,respectively,in the GRIP ice core data.

关键词：腾格里沙漠气候变异中国西北序列图粒度特征江段东亚冬季风湖相沉积

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