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Biomaterials-based anti-inflammatory treatment strategies for Alzheimer's disease

Neural Regeneration Research 2024年第1期19卷 100-115页

作者： Jianjian Chu Weicong Zhang Yan Liu Baofeng Gong Wenbo Ji Tong yin Chao Gao Danqi Liangwen Mengqi Hao Cuimin Chen Jianhua Zhuang Jie Gao You yin Department of Neurology Second Affiliated Hospital(Shanghai Changzheng Hospital)of Naval Medical UniversityShanghaiChina School of Pharmacy University College LondonLondonUK Department of Clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineClinical Pharmacy Innovation InstituteShanghai Jiao Tong University School of MedicineShanghaiChina School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghaiChina

The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.

关键词： Alzheimer's disease anti-inflammation blood-brain barrier drug delivery microglia nanoparticles neuroinflammation plant extracts

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Reservoir-forming conditions and key exploration & development techniques for Xushen gas field in Northeast China

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Petroleum Research 2019年第2期4卷 125-147页

作者： Fenglan Wang Yongzhuo Wang Xuemin Zhou changhai yin Ping Shu Baojun Cao yingkang Zhu Exploration and Development Research Institute Daqing Oilfield Co.Ltd.Daqing163712China

Exploration and development of volcanic gas reservoirs is a world-class problem,and less experience can be learned at home and abroad.Through study of reservoir-forming conditions of Xushen gas field,four sets of hydrocarbon source rocks,mainly mudstone and coal seam of Shahezi Formation,are identified in this gas field;its cap rocks are mudstone in Member 2 of Denglouku Formation,and Member 1 and Member 2 of Quantou Formation.By simulating reservoir-forming history,four filling periods of the Xushen gas field are determined,and the most favorable exploration targets are crater areas with structural highs,large thickness and good physical properties.On the basis of diagenetic mechanism study,the criteria of sequence series,lithology identification and reservoir types of gas reservoirs have been established;the volcanic rock bodies have been carefully depicted and the distribution laws of effective reservoirs of gas pools have been figured out.Based on evaluating reservoir-permeability characteristics of reservoirs,the gas well productivity characteristics(mainly type II,III and IV wells)have been identified,and the optimum design technology for volcanic gas reservoir development has been developed.The gas reservoirs in all blocks of Xushen gas field are classified into three types:singlebody gas reservoir model,disconnected multi-body gas reservoir model and interconnected multi-body gas reservoir model.Stimulation technologies,including multi-layer fracturing of vertical well,staged fracturing of open-hole horizontal well and volume fracturing,have been developed.According to gas well production performance,pressure change,well-controlled reserves and spatial distribution of volcanic bodies,combined with numerical simulation and prediction of gas reservoirs,the evaluation method of residual potential of volcanic gas reservoirs has been formed.Key technologies for effective exploration and development of complex volcanic gas reservoirs have been established and perfected,and bring good development effect.The rese

关键词： Xushen gas field Reservoireforming conditions Volcanic rock Development Productivity Optimum design

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Nanomaterials-mediated lysosomal regulation:a robust protein-clearance approach for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第2期20卷 424-439页

作者： Mengqi Hao Jianjian Chu Tinglin Zhang Tong yin Yuankai Gu Wendanqi Liang Wenbo Ji Jianhua Zhuang Yan Liu Jie Gao You yin Department of Neurology Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng Hospital)ShanghaiChina School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghaiChina Department of Clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the brain.Lysosomes,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular homeostasis.Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s disease.Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s disease.Currently,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and targeting.Recently,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical properties.This review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s disease.This review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal function.In conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s disease.The application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.

关键词： Alzheimer’s disease autophagy dysfunction lysosomal acidification lysosomal system nanomaterials neurodegenerative diseases

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Tunable polarization-drived high energy storage performances in flexible PbZrO_(3)films by growing Al_(2)O_(3)nanolayers

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Journal of Advanced Ceramics 2023年第11期12卷 2123-2133页

作者： Chao yin Tiandong Zhang Zhuangzhuang Shi Bowen Zhang changhai Zhang Qingguo Chi Key Laboratory of Engineering Dielectrics and Its Application Ministry of EducationHarbin University of Science and TechnologyHarbin 150080China School of Electrical and Electronic Engineering Harbin University of Science and TechnologyHarbin 150080China

In recent years,PbZrO_(3)(PZO)films have become favorable electric storage materials due to the unique electric field-induced phase transition behavior,but the severe hysteresis effect leads to low energy storage density and efficiency.In this work,inserting Al_(2)O_(3)(AO)insulation nanolayers is proposed to tune the polarization behavior of flexible PZO films,anticipating optimization of energy storage performance.The results show that the thickness of the AO nanolayers has a deep influence on the polarization behavior of the PZO films,and PZO/AO/PZO(PAP)sandwiched films with 8 nm AO interlayer deliver relaxor ferroelectric-like polarization instead of antiferroelectric counterpart.To further utilize the AO nanolayers as top/bottom layers,the linear-like polarization and the highest breakdown strength are achieved in the AO/PZO/AO/PZO/AO(APAPA8)multilayer films,leading to both high discharged energy storage density of 35.2 J/cm^(3) and efficiency of 92.9%,as well as excellent fatigue and bending endurance,good temperatures,and frequency stability.The tunable polarization induced by growing the AO nanolayers makes antiferroelectric PZO films have great potential to be used as energy storage dielectrics.

关键词： sol-gel flexible antiferroelectric polarization energy storage

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Tunable polarization-drived superior energy storage performance in PbZrO_(3) thin films

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Journal of Advanced Ceramics 2023年第5期12卷 930-942页

作者： Tiandong Zhang Zhuangzhuang Shi Chao yin changhai Zhang Yue Zhang Yongquan Zhang Qingguo Chen Qingguo Chi Key Laboratory of Engineering Dielectrics and Its Application Ministry of EducationHarbin University of Science and TechnologyHarbin 150080China Department of Materials Science and Engineering Korea Advanced Institute of Science and TechnologyDaejeon 305-701Republic of Korea

Antiferroelectric PbZrO_(3)(AFE PZO)films have great potential to be used as the energy storage dielectrics due to the unique electric field(E)-induced phase transition character.However,the phase transition process always accompanies a polarization(P)hysteresis effect that induces the large energy loss(Wloss)and lowers the breakdown strength(EBDS),leading to the inferior energy storage density(Wrec)as well as low efficiency.In this work,the synergistic strategies by doping smaller ions of Li^(+)–Al^(3+)to substitute Pb2+and lowering the annealing temperature(T)from 700 to 550℃are proposed to change the microstructures and tune the polarization characters of PZO films,except to dramatically improve the energy storage performances.The prepared Pb_((1−x))(Li_(0.5)Al_(0.5))_(x)ZrO_(3)(P_((1−x))(L_(0.5)A_(0.5))_(x)ZO)films exhibit ferroelectric(FE)-like rather than AFE character once the doping content of Li^(+)–Al^(3+)ions reaches 6 mol%,accompanying a significant improvement of W_(rec) of 49.09 J/cm^(3),but the energy storage efficiency(η)is only 47.94%due to the long-correlation of FE domains.Accordingly,the low-temperature annealing is carried out to reduce the crystalline degree and the P loss.P_(0.94)(L_(0.5)A_(0.5))_(0.06)ZO films annealed at 550℃deliver a linear-like polarization behavior rather than FE-like behavior annealed at 700℃,and the lowered remanent polarization(P_(r))as well as improved E_(BDS)(4814 kV/cm)results in the superior Wrec of 58.7 J/cm^(3) and efficiency of 79.16%,simultaneously possessing excellent frequency and temperature stability and good electric fatigue tolerance.

关键词： lead zirconate ionic pair polarization breakdown strength energy storage

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中药活性成分诱导肿瘤细胞铁死亡的研究进展

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中国实验方剂学杂志 2024年第9期30卷 245-253页

作者：张慧中张艺博付京黄华婷阮意丹尹兴斌曲昌海倪健董晓旭北京中医药大学中药学院北京102488 首都医科大学附属北京中医医院北京市中医药研究所北京100010

铁死亡是一种不同于细胞凋亡、细胞坏死、细胞自噬的新型细胞程序性死亡方式,与多种生理和病理过程有密切的联系。铁介导的活性氧积累是铁死亡发生的主要原因,铁死亡的发生机制与细胞内脂质代谢、铁代谢和抗氧化防御系统途径相关,多条... 详细信息

铁死亡是一种不同于细胞凋亡、细胞坏死、细胞自噬的新型细胞程序性死亡方式,与多种生理和病理过程有密切的联系。铁介导的活性氧积累是铁死亡发生的主要原因,铁死亡的发生机制与细胞内脂质代谢、铁代谢和抗氧化防御系统途径相关,多条信号轴和众多调节因子联合调控铁死亡的发生和中断。研究发现铁死亡对肿瘤细胞的生长和增殖具有一定的调节作用,诱导肿瘤细胞铁死亡能够有效抑制肿瘤的生长、转移及多药耐药等,因此铁死亡针对各类肿瘤细胞的作用效果和机制途径成为抗癌研究的热点话题。与此同时,铁死亡诱导剂的研究迅速发展,已有多种铁死亡诱导剂应用于临床癌症化疗阶段,且疗效显著,因此铁死亡类抗癌药物的研究成为肿瘤治疗发展的新路线。中药活性成分如石蒜碱、齐墩果酸、双氢青蒿素、土槿皮乙酸、麦冬皂苷B等,能通过脂质代谢、铁代谢、胱氨酸/谷氨酸转运体系统或谷胱甘肽过氧化酶4/谷胱甘肽等途径诱导肿瘤细胞铁死亡,调控肿瘤疾病的发展进程,展现出巨大的临床治疗潜力。该文从信号通路和调节因子及作用特点等方面介绍铁死亡的代谢调控网络,并结合铁死亡发生机制的理论基础,对中药活性成分诱导肿瘤细胞铁死亡的研究进展进行综述,为中药活性成分抗肿瘤应用提供新策略。

关键词：铁死亡中药活性成分肿瘤细胞铁代谢作用机制

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重楼总皂苷的现代研究进展与展望

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中国实验方剂学杂志 2024年第1期30卷 232-243页

作者：张艺博张慧中付京阮意丹姚爱娜张萍芝尹兴斌曲昌海倪健董晓旭北京中医药大学中药学院北京102488 首都医科大学附属北京中医医院北京市中医药研究所北京100010

重楼具有清热解毒、消肿止痛、凉肝定惊的作用,重楼皂苷是重楼的主要活性成分。研究表明,重楼总皂苷抗肿瘤作用显著,对乳腺癌、肺癌、胃癌、肝癌等实体瘤和白血病等非实体瘤有明显的抑制作用,其机制与抑制肿瘤细胞增殖、迁移和侵袭,调... 详细信息

重楼具有清热解毒、消肿止痛、凉肝定惊的作用,重楼皂苷是重楼的主要活性成分。研究表明,重楼总皂苷抗肿瘤作用显著,对乳腺癌、肺癌、胃癌、肝癌等实体瘤和白血病等非实体瘤有明显的抑制作用,其机制与抑制肿瘤细胞增殖、迁移和侵袭,调控细胞周期,诱导凋亡和非凋亡的死亡途径,调节机体代谢与肿瘤微环境等密切相关。此外,重楼总皂苷在抗炎、抗氧化、抑菌、止血、缩宫等方面也表现出很好的药理活性。与此同时,重楼总皂苷可能诱导正常细胞凋亡、诱发炎症反应与氧化应激、导致机体代谢紊乱,近年来其肝损伤、生殖损伤、胃肠损伤、溶血等不良反应报道逐渐增多。药代动力学研究显示,不同给药方式的重楼总皂苷在机体内代谢存在着较大的差异,注射给药清除速度较快,口服则可能存在肝肠循环,同时由于溶解度低、并能激活P-糖蛋白(P-gp),导致其原型吸收差、在肠道渗透率和回收率低,影响重楼总皂苷的生物利用度,借助现代技术制备新剂型或新型载药系统一定程度上可提高其生物利用度。基于上述研究,该文将“重楼总皂苷”“Rhizoma Paridis Total Saponins”作为关键词,通过检索中国知网、维普、Web of Science等国内外中英文数据库,对重楼总皂苷的药理作用、药代动力学及不良反应展开综述,以期能为重楼总皂苷的研究开发及临床应用提供参考。

关键词：重楼总皂苷抗肿瘤药理作用药代动力学不良反应

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四川盆地中部合川—潼南地区茅二下亚段白云岩储层特征及成储机制

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海相油气地质 2024年第2期29卷 136-146页

作者：印长海师江波谭秀成王显东田小彬鞠林波韦裕琳汪海燕谭万仓肖笛李明隆杨文杰中国石油大庆油田有限责任公司勘探开发研究院黑龙江省大庆市163712 中国石油集团碳酸盐岩储层重点实验室大庆油田研究分室中国石油集团碳酸盐岩储层重点实验室西南石油大学研究分室

近年来四川盆地中部合川—潼南地区中二叠统茅二下亚段白云岩储层勘探取得了重要突破,但储层强非均质性制约了有利区带的预测。基于岩心和薄片观察、物性实验及地球化学分析,系统剖析茅二下亚段白云岩储层的基本特征,讨论白云岩的成因... 详细信息

近年来四川盆地中部合川—潼南地区中二叠统茅二下亚段白云岩储层勘探取得了重要突破,但储层强非均质性制约了有利区带的预测。基于岩心和薄片观察、物性实验及地球化学分析,系统剖析茅二下亚段白云岩储层的基本特征,讨论白云岩的成因和储层形成机制。结果表明:(1)茅二下亚段储集岩以针孔状白云岩与孔洞状白云岩为主,储集空间类型为晶间(溶)孔、溶洞和裂缝;储层类型为以裂缝-孔洞型为主,裂缝-孔隙型为辅;以片状喉道为主,孔喉配置关系中等,裂缝为主要的渗流通道;针孔状白云岩平均孔隙度为2.50%,平均渗透率为0.806×10^(-3)μm^(2),孔洞状白云岩平均孔隙度为4.32%,平均渗透率为1.047×10^(-3)μm^(2)。(2)高能滩相是白云岩储层形成的物质基础,多期岩溶作用是形成优质储层的关键。准同生期白云石化作用增强了岩石抗压实能力,有助于储层孔隙的保持;茅口组沉积末期热液白云石化以胶结充填先期孔隙为主,降低了白云岩的储集性能。

关键词：白云岩储层特征成储机制茅口组四川盆地

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儒家中庸思想在脉诊教学中的体现

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中国中医药现代远程教育 2024年第4期22卷 8-10页

作者：白龙朱珂朱晓晓史亚星王常海河南中医药大学中医学院(仲景学院) 河南郑州450046

儒家中庸之道,提倡万事万物要不偏不倚,遵循规律。这一思想贯穿在中医脉诊的理论之中。正常脉象特点为有胃、有神、有根,中医脉诊以平为期,强调脉象应不偏不倚,脉之阴阳五行无偏盛偏虚。脉以胃气为本。胃气一方面指代脾胃为后天之本,气... 详细信息

儒家中庸之道,提倡万事万物要不偏不倚,遵循规律。这一思想贯穿在中医脉诊的理论之中。正常脉象特点为有胃、有神、有根,中医脉诊以平为期,强调脉象应不偏不倚,脉之阴阳五行无偏盛偏虚。脉以胃气为本。胃气一方面指代脾胃为后天之本,气血生化之源;另一方面为脉象之准则,为脉象之“中”,以脉之胃气衡量脉象的偏倚和判断疾病的预后。

关键词：儒家中庸思想脉诊教学

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肝脏伴毛细血管增生的血管畸形4例临床病理学分析

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中华病理学杂志 2024年第4期53卷 387-389页

作者：尹书怡何妙侠徐晶晶丛文铭董辉王瀚海军军医大学长海医院病理科上海200433 海军军医大学东方肝胆外科医院病理科上海200438

目的探讨肝脏伴毛细血管增生的血管畸形临床病理特征。方法收集海军军医大学东方肝胆外科医院和长海医院2014年6月至2022年9月手术治疗的4例肝脏伴毛细血管增生的血管畸形患者信息,并复习文献。结果4例患者中男性1例,女性3例,平均年龄3... 详细信息

目的探讨肝脏伴毛细血管增生的血管畸形临床病理特征。方法收集海军军医大学东方肝胆外科医院和长海医院2014年6月至2022年9月手术治疗的4例肝脏伴毛细血管增生的血管畸形患者信息,并复习文献。结果4例患者中男性1例,女性3例,平均年龄33岁。3例单发,1例多发,最大径0.7~7.5 cm。大体检查,病变灰白灰红色,病变中央可见坏死。镜下观察,病变由毛细血管样和海绵状血管样管腔构成,前者衬覆肥胖且钉状突起的内皮细胞,后者衬覆扁平状内皮细胞,细胞无异型,间质呈富于细胞的纤维样。病变中央区退变显著,周边区见扩张扭曲的血管,边界可伴舌状突起。免疫组织化学表达CD34和ERG,Glut-1阴性,Ki-67阳性指数<5%。患者术后恢复良好。结论肝脏伴毛细血管增生的血管畸形是一种罕见的良性血管源性病变,毛细血管样和海绵状血管样管腔混合生长、毛细血管腔内钉状突起的内皮细胞、扩张扭曲的血管和Glut-1阴性是该病的重要提示。

关键词：毛细血管增生长海医院灰红色阳性指数纤维样血管畸形内皮细胞免疫组织化学

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