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Targeting proprotein convertase subtilisin/kexin type 9(PCSK9):from bench to bedside

Signal Transduction and Targeted Therapy 2024年第2期9卷 509-557页

作者： Xuhui Bao Yongjun Liang Hanman Chang Tianji Cai Baijie Feng Konstantin Gordon yuekun zhu Hailian Shi Yundong He Liyi Xie Institute of Therapeutic Cancer Vaccines Fudan University Pudong Medical CenterShanghaiChina Shanghai Key Laboratory of Regulatory Biology School of Life SciencesEast China Normal UniversityShanghaiChina Department of Oncology Fudan University Pudong Medical CenterShanghaiChina Center for Clinical Research Fudan University Pudong Medical CenterShanghaiChina Clinical Research Center for Cell-based Immunotherapy Fudan UniversityShanghaiChina Department of Pathology Duke University Medical CenterDurhamNCUSA Center for Medical Research and Innovation Fudan University Pudong Medical CenterShanghaiChina Institute for Food Safety and Health Illinois Institute of TechnologyChicagoILUSA Department of Sociology University of MacaoTaipaMacaoChina Medical Institute Peoples’Friendship University of RussiaMoscowRussia A.Tsyb Medical Radiological Research Center ObninskRussia Department of Colorectal Surgery The First Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina Shanghai Key Laboratory of Compound Chinese Medicines Institute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineZhangjiang Hi-tech ParkShanghaiChina Department of Radiation Oncology Fudan University Shanghai Cancer CenterShanghaiChina Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina

Proprotein convertase subtilisin/kexin type 9(PCSK9)has evolved as a pivotal enzyme in lipid metabolism and a revolutionary therapeutic target for hypercholesterolemia and its related cardiovascular diseases(CVD).This comprehensive review delineates the intricate roles and wide-ranging implications of PCSK9,extending beyond CVD to emphasize its significance in diverse physiological and pathological states,including liver diseases,infectious diseases,autoimmune disorders,and notably,cancer.Our exploration offers insights into the interaction between PCSK9 and low-density lipoprotein receptors(LDLRs),elucidating its substantial impact on cholesterol homeostasis and cardiovascular health.It also details the evolution of PCSK9-targeted therapies,translating foundational bench discoveries into bedside applications for optimized patient care.The advent and clinical approval of innovative PCSK9 inhibitory therapies(PCSK9-iTs),including three monoclonal antibodies(Evolocumab,Alirocumab,and Tafolecimab)and one small interfering RNA(siRNA,Inclisiran),have marked a significant breakthrough in cardiovascular medicine.These therapies have demonstrated unparalleled efficacy in mitigating hypercholesterolemia,reducing cardiovascular risks,and have showcased profound value in clinical applications,offering novel therapeutic avenues and a promising future in personalized medicine for cardiovascular disorders.Furthermore,emerging research,inclusive of our findings,unveils PCSK9’s potential role as a pivotal indicator for cancer prognosis and its prospective application as a transformative target for cancer treatment.This review also highlights PCSK9’s aberrant expression in various cancer forms,its association with cancer prognosis,and its crucial roles in carcinogenesis and cancer immunity.In conclusion,this synthesized review integrates existing knowledge and novel insights on PCSK9,providing a holistic perspective on its transformative impact in reshaping therapeutic paradigms across various disorders.It emphasizes the clinical

关键词： PCSK9 metabolism convert

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市域列车救援工况溜逸风险分析及制动策略优化

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都市快轨交通 2024年第3期37卷 90-96页

作者：朱戡史月昆张小龙北京市轨道交通建设管理有限公司北京100068 城市轨道交通全自动运行系统与安全监控北京市重点实验室北京100068 北京轨道交通技术装备集团有限公司北京100068

针对市域铁路在运营过程中的救援场景研究缺乏及现有市域动车组能力不能完全满足救援的及时性要求等问题,本文研究了市域列车救援工况的溜逸风险及制动策略。首先,建立多编组列车连挂时的纵向动力学模型;然后,以北京大兴机场线为例,分... 详细信息

针对市域铁路在运营过程中的救援场景研究缺乏及现有市域动车组能力不能完全满足救援的及时性要求等问题,本文研究了市域列车救援工况的溜逸风险及制动策略。首先,建立多编组列车连挂时的纵向动力学模型;然后,以北京大兴机场线为例,分析在救援工况下现有运营方式可能带来的列车溜逸风险;最后,结合相关标准,分析救援过程不同制动模式下乘客的舒适性。研究结果表明:在33‰坡道上救援车以5 km/h连挂时,保持制动模式下列车加速度和冲击率将会达到10.5 m/s^(2)和9.9 m/s^(3),且发生溜逸,而采用紧急制动模式时,列车的加速度和冲击率分别下降了63.1%和54.7%,未发生溜逸;当救援车连挂速度降低至3 km/h后,列车最大加速度和最大冲击率分别降低至2.1 m/s^(2)和2.4 m/s^(3),乘客舒适性明显提高。在坡道停车时,由于存在制动-牵引切换过程,为保证在最大坡道上不溜车,列车保持制动力需达到60%最大常用制动力以上。

关键词：市域列车救援制动力溜逸冲击率

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TBL结合PBL教学法在胃肠外科教学查房中的应用

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中国继续医学教育 2024年第4期16卷 62-66页

作者：朱跃坤哈尔滨医科大学附属第一医院胃肠外科黑龙江哈尔滨150001

目的分析以团队为主导的教学法(team-based learning,TBL)结合以问题为主导的教学法(case-based learning,CBL)在胃肠外科教学查房中的应用效果。方法在2021年1月—2023年1月,于哈尔滨医科大学附属第一医院胃肠外科实习生60名,按随机双... 详细信息

目的分析以团队为主导的教学法(team-based learning,TBL)结合以问题为主导的教学法(case-based learning,CBL)在胃肠外科教学查房中的应用效果。方法在2021年1月—2023年1月,于哈尔滨医科大学附属第一医院胃肠外科实习生60名,按随机双盲法分为2组。对照组(n=30)采用常规教学,观察组(n=30)采用TBL结合PBL教学法。对比两组实习生的理论成绩、实践技能等。结果实习结束后,观察组的理论成绩、实践能力均高于对照组,差异有统计学意义(P<0.05)。观察组学习意识、学习行为、学习策略、学习评价及人际关系学习能力分别均高于对照组,差异有统计学意义(P<0.05)。观察组实习生的识别危机征象、医疗措施干预、团队分工合作、救治完成时间得分均高于对照组,差异有统计学意义(P<0.05)。观察组对本次教学评价的满意率96.67%高于对照组的73.33%,差异有统计学意义(P<0.05)。结论TBL结合PBL教学法用于胃肠外科教学查房中,能提高实习生的实践技能,取得较好的理论成绩,值得应用。

关键词：胃肠外科教学查房 TBL CBL 理论成绩实践技能

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慢传输型便秘分子机制研究及临床应用现状

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中华消化病与影像杂志（电子版） 2024年第1期14卷 82-89页

作者：黄涔朱跃坤哈尔滨医科大学附属第一医院结直肠外科 150001

慢性便秘是最常见的胃肠道症状之一,而慢传输型便秘是各类型慢性便秘中最难治疗的,慢传输型便秘以结肠传输延迟为特征,无出口梗阻,当药物难以治疗后,则需要结肠切除术或次全切术。慢传输型便秘病因机制复杂,致病机制目前尚未明确,研究... 详细信息

慢性便秘是最常见的胃肠道症状之一,而慢传输型便秘是各类型慢性便秘中最难治疗的,慢传输型便秘以结肠传输延迟为特征,无出口梗阻,当药物难以治疗后,则需要结肠切除术或次全切术。慢传输型便秘病因机制复杂,致病机制目前尚未明确,研究主要集中于肠道神经系统的病理改变、胃肠Cajal间质细胞改变、神经递质和胃肠激素的异常、肠内液体吸收等的影响。现在许多新的研究方法蓬勃发展,有希望为慢传输型便秘发病机制的深入研究提供新的思路。

关键词：慢传输型便秘分子机制

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Functionalized Fiber-Based Strain Sensors:Pathway to Next-Generation Wearable Electronics

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Nano-Micro Letters 2022年第4期14卷 90-128页

作者： Zekun Liu Tianxue zhu Junru Wang Zijian Zheng Yi Li Jiashen Li yuekun Lai Department of Materials The University of ManchesterOxford RoadManchester M139PLUK College of Chemical Engineering Fuzhou UniversityFuzhou 350116China Institute of Textiles and Clothing Research Institute for Intelligent Wearable SystemsResearch Institute for Smart EnergyThe Hong Kong Polytechnic UniversityHung HomHong KongSARChina

Wearable strain sensors are arousing increasing research interests in recent years on account of their potentials in motion detection,personal and public healthcare,future entertainment,man-machine interaction,artificial intelligence,and so forth.Much research has focused on fiber-based sensors due to the appealing performance of fibers,including processing flexibility,wearing comfortability,outstanding lifetime and serviceability,low-cost and large-scale capacity.Herein,we review the latest advances in functionalization and device fabrication of fiber materials toward applications in fiber-based wearable strain sensors.We describe the approaches for preparing conductive fibers such as spinning,surface modification,and structural transformation.We also introduce the fabrication and sensing mechanisms of state-of-the-art sensors and analyze their merits and demerits.The applications toward motion detection,healthcare,man-machine interaction,future entertainment,and multifunctional sensing are summarized with typical examples.We finally critically analyze tough challenges and future remarks of fiber-based strain sensors,aiming to implement them in real applications.

关键词： Wearable strain sensor Fiber functionalization Wearability Flexible electronics Conductive materials

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Flexible electrochromic fiber with rapid color switching and high optical modulation

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Nano Research 2023年第4期16卷 5473-5479页

作者： Tianxue zhu Jiaqing Xiong Jingwei Chen Xinran Zhou Guofa Cai yuekun Lai Pooi See Lee National Engineering Laboratory for Modern Silk College of Textile and Clothing EngineeringSoochow UniversitySuzhou 215123China School of Materials Science and Engineering Nanyang Technological University50 Nanyang AvenueSingapore 639798Singapore College of Chemical Engineering Fuzhou UniversityFuzhou 350116China Qingyuan Innovation Laboratory Quanzhou 362801China Innovation Center for Textile Science and Technology Donghua UniversityShanghai 201620China

Though flexible electrochromic devices have shown huge potential application in the fields of safety warning,display and smart windows,limited attention was paid on preparing flexible electrochromic fiber because of the difficulty in fabricating the multilayer electrochromic device structure in one-dimensional form.In this study,a flexible electrochromic nylon fiber based on Ag nanowires(NWs)/PEDOT:PSS/WO3 nanoparticles(NPs)(PEDOT:PSS=poly(3,4-ethylenedioxythiophene):polystyrenesulfonic acid)is successfully fabricated,delivering rapid color switching(2.5 and 9 s for bleaching and coloration)and high optical modulation(65.5%at 633 nm),and sustainable to repeated mechanical deformations.Ag NWs,PEDOT:PSS and WO3 NPs were dip-coated on the nylon fiber,resulting in an electrochromic fiber electrode with stable fiber resistance of 50-100Ω/10 cm,which can withstand mechanical deformation against 300 times of bending cycles with bending radius of 0.5 cm,and sustain 30 times of tape-peeling.During the galvanostatic tests,the capacitance of the electrochromic electrode can maintain 70%of the initial value even after 5,000 times of charge-discharge cycles.Even in knotted shape,the fiber still shows excellent color contrast.This study provides a novel method to construct flexible electrochromic fiber and pave the way for the development of flexible optoelectronic devices,such as flexible and wearable displays.

关键词： flexible electrochromic fiber WO3 nanoparticle

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Multifunctional hydrophobic fabric-based strain sensor for human motion detection and personal thermal management

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Journal of Materials Science & Technology 2023年第7期138卷 108-116页

作者： Tianxue zhu Lexin Liu Jianying Huang Shuhui Li Yonggang Lei Weilong Cai yuekun Lai Huaqiong Li College of Chemical Engineering Fuzhou UniversityFuzhou 350116China Zhejiang Engineering Research Center for Tissue Repair Materials Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325000China Department of Chemistry University College LondonLondon WC1E 6BTUK Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou 325000China

Multifunctional flexible devices for human motion detection and thermal management raised great at-tention as the problem of the aging population is becoming more and more serious.However,it is still a challenge to endow the devices with excellent stability and wide application scope.Here we prepared a hydrophobic and conductive fabric-based strain sensor for smart fabric via successively coating with poly-dopamine(PDA),polyaniline(PANI),polypyrrole(PPy),and polydimethylsiloxane(PDMS)through in-situ polymerization and dip-coating,which could be used for strain sensor and wearable heater both in air and underwater.The obtained sample exhibited a fast electrical response in 500 ms and could withstand 10,000 times stretching-releasing cycles,additionally,the sample exhibited satisfactory electro-thermal and photo-thermal performances.As a whole,the multifunctional fabric-based devices with excellent performances show great potential to be applied in medical monitoring and personal care,especially for aged and disabled persons.

关键词： Strain sensor Superhydrophobic Thermal management Photo-thermal device

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Surface plasmon resonance metal-coupled biomass carbon modified TiO_(2) nanorods for photoelectrochemical water splitting

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Chinese Journal of Chemical Engineering 2022年第1期35卷 403-411页

作者： Yingzhen Zhang Yonggang Lei Tianxue zhu Zengxing Li Shen Xu Jianying Huang Xiao Li Weilong Cai yuekun Lai Xiaojun Bao National Engineering Research Center of Chemical Fertilizer Catalyst(NERC-CFC) College of Chemical EngineeringFuzhou UniversityFuzhou 350116China Fujian Science&Technology Innovation Laboratory for Chemical Engineering of China Quanzhou 362114China

Exploring efficient and stable photoanode materials is a necessary link to realize the practical application of solar-driven photoelectrochemical(PEC)water splitting.Hence,we prepared rutile TiO_(2) nanorods,with a width of 50 nm,which was growth in situ on carbon cloth(TiO_(2)@CC)by hydrothermal reaction.And then,Ag nanoparticles(NPs)and biomass N,S-C NPs were chosen for the additional modification of the fabricated TiO_(2) nanorods to produce broccoli-like Ag-N,S-C/TiO_(2)@CC nanocomposites.According to the result of ultraviolet-visible diffuse reflectance spectroscopy(UV-vis)and PEC water splitting performance tests,Ag-N,S-C/TiO_(2)@CC broadens the absorption region of TiO_(2)@CC from the ultraviolet region to the visible regio n.Under AM 1.5 G solar light irradiation,the photocurrent density of Ag-N,S-C/TiO_(2)@CC is 89.8μA·cm^(-2),which is 11.8 times higher than TiO_(2)@CC.Under visible light irradiation,the photocurrent density of Ag-N,S-C/TiO_(2)@CC reaches to 12.6μA·cm^(-2),which is 21.0 times higher than TiO_(2)@CC.Moreover,Ag-N,S-C/TiO_(2)@CC shows a photocurrent responses in full pH range.It can be found that Ag NPs and N,S-C NPs play key roles in broaden the absorption range of TiO_(2) nanorods to the visible light region and,promote the occurrence of PEC water oxidation reaction due to the surface plasmon resonance effect of Ag NPs and the synergistic effect of N,S-C NPs.The mechanism demonstrated that Ag-N,S-C/TiO_(2)@CC can separate the photogenerated electron-hole pairs effectively and transfer the photogenerated electrons to the photocathode(Pt plate)in time.This research provides a new strategy for exploration surface plasma metal coupled biomass carbon materials in the field of PEC water splitting.

关键词： Photoelectrochemical Water oxidation Ag-N,S-C/TiO_(2) Surface plasmon resonance Biomass carbon

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梗阻性左半结肠癌的治疗现状与争议

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中国肿瘤临床 2022年第5期49卷 264-267页

作者：杨修丁(综述) 朱跃坤(综述) 朴大勋(审校) 哈尔滨医科大学附属第一医院普外科哈尔滨市150001

结直肠癌是常见的消化系统恶性肿瘤。结直肠癌合并梗阻的概率达20%,其中有70%发生在左半结肠。针对梗阻性左半结肠癌的治疗目前未达成共识。面对恶性梗阻患者,临床通常选择紧急手术或者自体膨胀性金属支架植入后择期手术。紧急手术可及... 详细信息

结直肠癌是常见的消化系统恶性肿瘤。结直肠癌合并梗阻的概率达20%,其中有70%发生在左半结肠。针对梗阻性左半结肠癌的治疗目前未达成共识。面对恶性梗阻患者,临床通常选择紧急手术或者自体膨胀性金属支架植入后择期手术。紧急手术可及时切除肿瘤,但是却带来高死亡率和并发症率;金属支架植入极大降低了危险并发症的概率,但是对远期预后的改善并没有明显提高。而选择手术时又面临分期手术还是一期肠切除吻合术的抉择,分期手术患者花费高,一期肠切除吻合术吻合口瘘风险高。如何选择最有利于患者的治疗方式取决于外科医生的临床决策能力,同时也需要开展更多的多中心临床研究。本文就梗阻性左半结肠癌的治疗现状与争议进行综述。

关键词：左半结肠癌肠梗阻急诊手术自体膨胀性金属支架

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新时期国土空间近期规划创新思考——以北京为例

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城市发展研究 2023年第10期30卷 1-7页

作者：和朝东黄晓春陈科比谷月昆朱洁北京市城市规划设计研究院

新版北京城市总体规划经党中央、国务院正式批复以来，全面推动规划实施成为全市的重点工作，近期规划作为实施总规的关键环节，如何通过改革创新，科学高效引领规划实施工作，成为规划实施工作的核心。首先对北京近期规划的发展演变进... 详细信息

新版北京城市总体规划经党中央、国务院正式批复以来，全面推动规划实施成为全市的重点工作，近期规划作为实施总规的关键环节，如何通过改革创新，科学高效引领规划实施工作，成为规划实施工作的核心。首先对北京近期规划的发展演变进行了回顾，分析其技术特点以及存在问题；其次从总规实施事前、事中、事后三个阶段深入剖析了当前总规实施中存在的主要问题；在此基础上，提出近期规划作为总规实施综合平台应着重处理好的几个关系，具体包括长远与近期、空间与时间、上下与左右、整体与局部、动态与静态、政府与市场等；最后，针对新时期总规实施要求以及近期规划的特点和目标，从统筹时空的编制体系、相辅相成的规划成果体系、协同高效的多规统筹项目平台、贯通一体的实施评估监督体系等几个方面提出了近期规划创新的主要内容。

关键词：国土空间近期规划总体规划实施规划创新

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