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Structure-Based Drug Design and Identification of H₂O-Soluble and Low Toxic Hexacyclic Camptothecin Derivatives with Improved Efficacy in Cancer and Lethal Inflammation Models in Vivo

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JOURNAL OF MEDICINAL CHEMISTRY 2018年第19期61卷 8613-8624页

作者： Pang, Peichen Chen, Jiean Li, Xijian Li, Miyang Yu, Huidong Zhao, Jean J. Ni, Jing Wang, xuwen Sun, Huiyong Tian, Sheng Zhu, Feng liu, Feng Huang, Yong Hou, Tingjun Zhejiang Univ Coll Pharmaceut Sci Hangzhou 310058 Zhejiang Peoples R China Zhejiang Univ State Key Lab CAD&CG Hangzhou 310058 Zhejiang Peoples R China Peking Univ State Key Lab Chem Oncogen Key Lab Chem Genom Shenzhen Grad Sch Shenzhen 518055 Guangdong Peoples R China Rongene Pharma Co Ltd Guangzhou 510663 Guandong Peoples R China Dana Farber Canc Inst Dept Canc Biol Boston MA 02215 USA Harvard Med Sch Dept Biol Chem & Mol Pharmacol Boston MA 02215 USA Soochow Univ Coll Pharmaceut Sci Suzhou 215123 Jiangsu Peoples R China

Camptothecin (CPT) has been shown to block disassembly of the topoisomerase I (Topo I)/DNA cleavable complex. However, the poor aqueous solubility, intrinsic instability, and severe toxicity of CPTs have limited their clinical applications. Herein, we report the design and synthesis of H2O-soluble and orally bioavailable hexacyclic CPT derivatives. By analysis of a virtual chemical library and cytotoxicity screening in vitro, 9 and 11 were identified as potential prodrugs and chosen for further characterization in vivo. Both compounds exhibited remarkable anticancer and anti-inflammation efficacies in animals and improved drug-like profiles.

关键词： Mixtures Rodent models Solubility Genetics Toxicity

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改良Burks-Schaffer入路切开复位空心钉固定与关节镜下Endobutton带袢钢板固定治疗后交叉韧带胫骨止点撕脱骨折的疗效比较

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中华创伤骨科杂志 2019年第5期21卷 378-383页

作者：刘炜洁陈峰叶发刚戚超宫海峰张成栋王开钱源李绪文青岛大学附属医院创伤外科 266000

目的通过分析比较改良Burks-Schaffer入路切开复位空心钉固定与关节镜下Endobutton带袢钢板固定治疗后交叉韧带(PCL)胫骨止点撕脱骨折的临床疗效。方法回顾性分析2013年2月至2017年8月青岛大学附属医院创伤外科收治的41例PCL胫骨止点撕... 详细信息

目的通过分析比较改良Burks-Schaffer入路切开复位空心钉固定与关节镜下Endobutton带袢钢板固定治疗后交叉韧带(PCL)胫骨止点撕脱骨折的临床疗效。方法回顾性分析2013年2月至2017年8月青岛大学附属医院创伤外科收治的41例PCL胫骨止点撕脱骨折患者资料。男24例,女17例;年龄18~65岁,平均39岁;左膝22例,右膝19例;根据固定方式不同将患者分为2组:改良切开组23例(行改良Burks-Schaffer入路切开复位空心钉固定),关节镜组18例(行关节镜下Endobutton带袢钢板固定)。术后比较两组患者的手术时间、出血量、膝关节各项客观评分及膝关节活动度(ROM)等情况。结果41例患者术后获23~40个月(平均27.2个月)随访。所有患者均未出现切口感染、骨折畸形愈合或不愈合、固定装置松动等并发症。末次随访时膝关节X线片示撕脱骨折均已达到骨性愈合标准。改良切开组与关节镜组手术时间分别为(52.6±7.3)、(86.8±9.2)min,出血量分别为(63.9±12.7)、(19.7±10.2)mL,以上项目两组间比较差异均有统计学意义(P<0.05)。而两组患者在膝关节各项客观评分及ROM方面差异均无统计学意义(P>0.05)。结论改良Burks-Schaffer入路切开复位空心钉固定与关节镜下Endobutton带袢钢板固定治疗PCL胫骨止点撕脱骨折均能获得满意效果,后者出血少,但前者在手术时间方面更具优势。

关键词：膝关节关节镜检查骨折固定术,内后交叉韧带胫骨止点撕脱骨折改良Burks-Schaffer入路

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相干布局囚禁原子钟原子气室内部缓冲气体组分的优化

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激光与光电子学进展 2019年第12期56卷 30-35页

作者：李云超胡旭文张璐刘召军张开放牟仕浩闫树斌张彦军中北大学仪器与电子学院山西太原030051 中北大学仪器科学与动态测试教育部重点实验室山西太原030051

频率稳定度是评价相干布局囚禁(CPT)原子钟性能的重要指标,而原子气室内部缓冲气体的种类及其气压比是影响CPT原子钟频率稳定度的主要因素。选用Ar与N2为缓冲气体,从理论上对其温度频移特性进行仿真分析,并在不同缓冲气体气压比例的条... 详细信息

频率稳定度是评价相干布局囚禁(CPT)原子钟性能的重要指标,而原子气室内部缓冲气体的种类及其气压比是影响CPT原子钟频率稳定度的主要因素。选用Ar与N2为缓冲气体,从理论上对其温度频移特性进行仿真分析,并在不同缓冲气体气压比例的条件下实验测量了CPT原子钟的温度频移特性。根据理论与实验结果确定了原子气室内部缓冲气体最佳的比例,并给出了与之对应的最小温度频移工作点。研究结果对设计CPT原子钟原子气室内部的缓冲气体气压比及其工作温度具有借鉴作用。

关键词：原子与分子物理原子钟原子气室频率稳定度温度频移

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慢性阻塞性肺部疾病早期脑部灰、白质VBM及DTI研究

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医学影像学杂志 2020年第6期30卷 938-942页

作者：钟敏之曾旭文李新春邹文锦邹乔步军刘晓雯广东省广州市红十字会医院放射科广东广州510220 广州医科大学第一附属医院放射科广东广州510210 广州医科大学附属脑科医院放射科广东广州510370

目的运用基于体素形态学分析(voxel-based morphometry,VBM)及弥散张量成像(diffusion tensor imaging,DTI)技术探讨慢性阻塞性肺气肿(chronic obstructive pulmonary disease,COPD)患者慢性缺氧所致的脑灰、白质结构病理变化。方法收集COPD患者30例及年龄相匹配的正常志愿者30例。所有入组者均运用Philips 3.0T MR进行T2、FLair,DTI及全脑3D-T1WI。运用VBM8软件处理,得到全脑灰质密度数据参数图。利用Philips工作站处理DTI信息,勾画出长联络纤维。以VBM结果所得灰质减少区为种子勾画弓状纤维,测量白质纤维束的FA、ADC值。一般资料及FA、ADC计数资料对比均应用SPSS 17.0进行t检验统计分析。结果VBM结果显示,COPD患者组对比正常组,全脑多个区域灰质密度减小,包括右侧颞下回、右侧额眶回、左侧海马旁回、右侧颞极、双侧尾状核、双侧前运动皮层、左侧缘上回、右侧岛叶。DTI测量示:双侧尾状核FA值,右侧岛叶,双侧皮质脊髓束、左侧扣带束、左侧勾束FA降低,P<0.005。结论COPD患者脑区存在多个灰、白质区域异常,提示COPD患者在常规MRI未出现异常情况下已有微观脑结构改变。VBM及DTI技术可检测疾病早期脑结构病理改变,对临床评估有一定意义。

关键词：慢性阻塞性肺部疾病基于体素形态学分析灰质白质磁共振成像

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Effect of stamping deformation on microstructure and properties evolution of an Al-Mg-Si-Cu alloy for automotive panels

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JOURNAL OF MATERIALS SCIENCE 2017年第10期52卷 5569-5581页

作者： Yang, Mingjun liu, Siliang He, xuwen Wang, Jiong Kong, Yi Zhao, Pizhi Li, Kai Du, Yong Cent S Univ State Key Lab Powder Met Changsha 410083 Peoples R China Suzhou Res Inst Nonferrous Met Dept Fabricat Proc & Technol Aluminum Alloys Suzhou 215026 Peoples R China CHINALCO Res Inst Sci & Technol Dept Fabricat Proc & Technol Aluminum Alloys Beijing 100082 Peoples R China Cent S Univ Inst Mat Microstruct Changsha 410083 Peoples R China

The effect of 5 % tensile deformation, which simulates the stamping process of Al-Mg-Si-Cu automotive outer panels, on the microstructural evolution during age strengthening, has been investigated. In addition, its benefit on key mechanical properties including hardness, yield strength, ductility, and corrosion resistance has been linked to the microstructural features. It was found that the aging precipitation sequence, SSSS -> clusters and G.P. zones -> beta aEuro(3) -> beta' + Q' -> Q, was not influenced by the dislocations introduced through the stamping deformation prior to aging. On the other hand, stamping deformation could promote the formation of precipitates and refine the precipitates because of the enhanced heterogeneous nucleation and the accelerated precipitation kinetics, leading to superior strength of the alloy at the early stage. Meanwhile, the larger amount of Cu incorporated into nanoprecipitates leads to better intergranular corrosion resistance of the stamped alloy compared with the unstamped one. Due to the reduction in free Si amount at grain boundaries, the formation of fine subgrain structures and the increase of dislocation accumulation, the ductility of the stamped alloy was increased.

关键词： ALUMINUM-magnesium-silicon alloys DEFORMATIONS (Mechanics) METAL microstructure TENSILE strength DISLOCATIONS in crystals

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SERIES OF DIMERIC INDOLE ALKALOID COMPOUNDS, PREPARATION METHOD THEREFOR AND USE OF SAME IN PREPARATION OF ANTIBACTERIAL DRUGS

SERIES OF DIMERIC INDOLE ALKALOID COMPOUNDS, PREPARATION MET...

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作者： GUO, Yuewei LAN, Lefu LI, xuwen CHEN, Feifei liu, Jin

标准号: WO2019072112(A1)

The present invention falls within in the fields of organic synthesis and pharmaceutical chemistry. In particular, the present invention relates to a series of dimeric indole alkaloid compounds as shown in structural general formula I, preparation methods therefor and the use of same in the preparation of antibacterial drugs. After same undergo in vitro activity screening, the results show that such compounds have strong antibacterial activity, in particular have specific inhibitory effects on gram-positive bacteria, such as strains of staphylococcus, bacillus and enterococcus, and related drug-resistant strains thereof, and can be used as the lead compounds for developing new antibacterial drugs.

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Correction: CEPC Technical Design Report: Accelerator

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Radiation Detection Technology and Methods 2024年第1期9卷 184-192页

作者： Abdallah, Waleed de Freitas, Tiago CarlosAdorno Afanaciev, Konstantin Ahmad, Shakeel Ahmed, Ijaz Ai, Xiaocong Aleem, Abid Altmannshofer, Wolfgang Alves, Fabio An, Weiming An, Rui Anderle, Daniele Paolo Antusch, Stefan Arai, Yasuo Arbuzov, Andrej Arhrib, Abdesslam Ashry, Mustafa Bai, Sha Bai, Yu Bai, Yang Bairathi, Vipul Balazs, Csaba Bambade, Philip Ban, Yong Bandyopadhyay, Triparno Bao, Shou-Shan Barber, Desmond P. Bat, Ays¸e Batozskaya, Varvara Behera, Subash Chandra Belyaev, Alexander Bertucci, Michele Bi, Xiao-Jun Bi, Yuanjie Bian, Tianjian Bianchi, Fabrizio Bieko¨tter, Thomas Biglietti, Michela Bilanishvili, Shalva Binglin, Deng Bodrov, Denis Bogomyagkov, Anton Bondarenko, Serge Boogert, Stewart Boonekamp, Maarten Borri, Marcello Bosotti, Angelo Boudry, Vincent Boukidi, Mohammed Boyko, Igor Bozovic, Ivanka Bozzi, Giuseppe Brient, Jean-Claude Budzinskaya, Anastasiia Bukhari, Masroor Bytev, Vladimir Cacciapaglia, Giacomo Cai, Hua Cai, Wenyong Cai, Wujun Cai, Yijian Cai, Yizhou Cai, Yuchen Cai, Haiying Cai, Huacheng Calibbi, Lorenzo Cang, Junsong Cao, Guofu Cao, Jianshe Chance, Antoine Chang, Xuejun Chang, Yue Chang, Zhe Chang, Xinyuan Chao, Wei Chatrabhuti, Auttakit Che, Yimin Che, Yuzhi Chen, Bin Chen, Danping Chen, Fuqing Chen, Fusan Chen, Gang Chen, Guoming Chen, Hua-Xing Chen, Huirun Chen, Jinhui Chen, Ji-Yuan Chen, Kai Chen, Mali Chen, Mingjun Chen, Mingshui Chen, Ning Chen, Shanhong Chen, Shanzhen Chen, Shao-Long Chen, Shaomin Chen, Shiqiang Chen, Tianlu Chen, Wei Chen, Xiang Chen, Xiaoyu Chen, Xin Chen, Xun Chen, Xurong Chen, Ye Chen, Ying Chen, Yukai Chen, Zelin Chen, Zilin Chen, Boping Chen, Chunhui Cheng, Hok Chuen Cheng, Huajie Cheng, Shan Cheng, Tongguang Chi, Yunlong Chimenti, Pietro Chiu, Wen Han Cho, Guk Chu, Ming-Chung Chu, Xiaotong Chu, Ziliang Coloretti, Guglielmo Crivellin, Andreas Cui, Hanhua Cui, Xiaohao Cui, Zhaoyuan D’Anzi, Brunella Dai, Ling-Yun Dai, Xinchen Dai, xuwen De Maria, Antonio De Filippis, Nicola De La Taille, Christophe De Mori, Francesca De Sio, Chiara Del Core, Elisa Deng, Cairo University Giza Egypt Xi’an Jiaotong-Liverpool University Suzhou China Institute of Power Engineering of National Academy of Sciences of Belarus Minsk Belarus Pakistan Institute of Nuclear Science and Technology (PINSTECH) Islamabad Pakistan Applied Physics Department Science and Technology Federal Urdu University of Arts Islamabad Pakistan Zhengzhou University Zhengzhou China Institute of High Energy Physics Chinese Academy of Sciences Beijing China University of California Santa Cruz Santa Cruz USA Nanjing University Nanjing China Beijing Normal University Beijing China Harvard University Cambridge USA South China Normal University Guangzhou China University of Basel Basel Switzerland High Energy Accelerator Research Organization (KEK) Tsukuba Japan Joint Institute for Nuclear Research Dubna Russia Faculty of Sciences and Techniques Université Abdelmalek Essaadi Tangier Morocco Southeast University Nanjing China Department of Physics University of Wisconsin–Madison Madison USA Instituto de Alta Investigación Universidad de Tarapacá Arica Chile Monash University Melbourne Australia Laboratoire de Physique des 2 infinis Irène Joliot-Curie – IJCLab Orsay France Peking University Beijing China Department of Physics and Nanotechnology SRM Institute of Science and Technology Kattankulathur India Shandong University Jinan China University of New Mexico Albuquerque USA Bandirma Onyedi Eylul University Bandırma Turkey National Centre for Nuclear Research Warsaw Poland Indian Institute of Technology Madras (IN) Chennai India University of Southampton Southampton UK INFN Milano - LASA Segrate Italy Sun Yat-Sen University Guangzhou China China Institute of Atomic Energy Beijing China INFN-University of Torino Turin Italy Karlsruhe Institute of Technology Institute for Theoretical Physics Karlsruhe Germany INFN-Sezione di Roma Tre Rome Italy Kutaisi International University Kutaisi Georgia Soochow University Suzhou China Budker Institute

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A novel injectable calcium phosphate-based nanocomposite for the augmentation of cannulated pedicle-screw fixation

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INTERNATIONAL JOURNAL OF NANOMEDICINE 2017年第20170427期12卷 3395-3406页

作者： Sun, Haolin liu, Chun liu, Huiling Bai, Yanjie Zhang, Zheng Li, xuwen Li, Chunde Yang, Huilin Yang, Lei Peking Univ Dept Orthoped Hosp 1 8 Xishiku St Beijing 100034 Peoples R China Soochow Univ Inst Orthoped Dept Orthoped Affiliated Hosp 1 Suzhou Peoples R China Soochow Univ Sch Publ Hlth Med Coll Suzhou Peoples R China Soochow Univ IRCTO Suzhou Peoples R China

Polymethyl methacrylate (PMMA)-augmented cannulated pedicle-screw fixation has been routinely performed for the surgical treatment of lumbar degenerative diseases. Despite its satisfactory clinical outcomes and prevalence, problems and complications associated with high-strength, stiff, and nondegradable PMMA have largely hindered the long-term efficacy and safety of pedicle-screw fixation in osteoporotic patients. To meet the unmet need for better bone cement for cannulated pedicle-screw fixation, a new injectable and biodegradable nanocomposite that was the first of its kind was designed and developed in the present study. The calcium phosphate-based nanocomposite (CPN) exhibited better anti-pullout ability and similar fluidity and dispersing ability compared to clinically used PMMA, and outperformed conventional calcium phosphate cement (CPC) in all types of mechanical properties, injectability, and biodegradability. In term of axial pullout strength, the CPN-augmented cannulated screw reached the highest force of similar to 120 N, which was higher than that of PMMA (similar to 100 N) and CPC (similar to 95 N). The compressive strength of the CPN (50 MPa) was three times that of CPC, and the injectability of the CPN reached 95%. In vivo tests on rat femur revealed explicit biodegradation of the CPN and subsequent bone ingrowth after 8 weeks. The promising results for the CPN clearly suggest its potential for replacing PMMA in the application of cannulated pedicle-screw fixation and its worth of further study and development for clinical uses.

关键词： calcium phosphate nanocomposite injectable biodegradable pedicle screw lumbar degenerative disease osteoporosis

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早熟杂交棉金垦杂1062号选育及栽培技术

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中国棉花 2019年第5期46卷 37-38页

作者：孔宪辉余渝王旭文刘丽王娟新疆农垦科学院棉花研究所/棉花遗传改良与高产栽培兵团重点实验室新疆石河子832000

金垦杂1062是新疆农垦科学院棉花研究所选育的早熟陆地棉杂交种。本文概述了该杂交种选育过程及在新疆早熟杂交棉区域试验和生产试验中植株性状、品质性状、产量性状特征和栽培管理技术要点。

关键词：杂交棉金垦1062号丰产优质

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脑震宁颗粒治疗脑外伤综合征的Meta分析

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山西中医药大学学报 2020年第3期21卷 157-160页

作者：范建新刘艳之刘海霞卫春红王将秦雪梅朱平王旭文李震宇山西大学中医药现代研究中心山西太原030006 山西大学化学化工学院山西太原030006 山西振东安特生物制药有限公司山西晋中030619

目的:利用Meta分析法系统评价脑震宁治疗脑外伤综合征的有效性。方法:检索中英文数据库,时间从建库至2019年7月。收集脑震宁治疗脑外伤综合征的随机对照试验(RCT),对纳入的文献使用RevMan 5.3软件进行Meta分析。结果:经过文献筛选共纳入... 详细信息

目的:利用Meta分析法系统评价脑震宁治疗脑外伤综合征的有效性。方法:检索中英文数据库,时间从建库至2019年7月。收集脑震宁治疗脑外伤综合征的随机对照试验(RCT),对纳入的文献使用RevMan 5.3软件进行Meta分析。结果:经过文献筛选共纳入6项研究,包含736例患者。文献质量评估结果显示文献总体质量不高,危险比(RR)及95%可信区间(95%CI)为1.41(1.29,1.53)。结论:脑震宁对脑外伤综合征有显著疗效,但亟须高质量的临床研究对其疗效和安全性加以确证。

关键词：脑外伤综合征脑震宁 Meta分析随机对照试验

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