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Clinical associations of corneal neuromas with ocular surface diseases

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Neural Regeneration Research 2024年第1期19卷 140-147页

作者： Charmaine Jan Li Toh Chang liu isabelle Xin Yu Lee Molly Tzu Yu Lin Louis Tong Yu-Chi liu Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore Singapore Eye Research Institute Singapore Department of Cornea and External Eye Disease Singapore National Eye CentreSingapore Ophthalmology and Visual Sciences Academic Clinical Program Duke-NUS Medical SchoolSingapore

Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or *** formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ***,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas *** recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface *** neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and *** this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment *** current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more *** imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.

关键词： cornea corneal diseases corneal nerve corneal neuropathy in vivo confocal microscopy microneuroma neuroma ocular surface diseases

Protein Phosphatase 2C of Toxoplasma Gondii Interacts with Human SSRP1 and Negatively Regulates Cell Apoptosis

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Biomedical and Environmental Sciences 2014年第11期27卷 883-893页

作者： GAO Xue Juan FENG Jun Xia ZHU Sen liu Xiao Hui TARDIEUX isabelle liu Lang Xia Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes Institute of Life and Health EngineeringJinan University Institut Cochin Université DescartesTeam FRM ‘Barriers and Pathogens’22 Rue Méchain

Objective The protozoan Toxoplasma gondii expresses large amounts of a 37 kDa Type 2C serine-threonine phosphatase,the so-called TgPP2 C which has been suggested to contribute to parasite growth *** expression in mammalian cells also indicated that the enzyme could regulate growth and *** this study,we aimed to investigate the interaction of TgPP2 C with human SSRP1（structure-specific recognition protein 1） and the effects of TgPP2 C on cell *** The yeast two hybrid system,His-tag pull-down and co-immunoprecipitation assays were used to confirm the interaction of TgPP2 C with SSRP1 and determine the binding domain on *** evaluation of cell apoptosis was performed using cleaved caspase-3 antibody and Annexin-V/PI kit combined with flow *** We identified human SSRP1 as an interacting partner of TgPP2 *** C-terminal region of SSRP1 including the amino acids 471 to 538 was specifically mapped as the region responsible for interaction with TgPP2 *** overexpression of TgPP2 C down-regulated cell apoptosis and negatively regulated apoptosis induced by DRB,casein kinase II（CKII） inhibitor,through enhanced interaction with *** TgPP2 C may be a parasitic factor capable of promoting cell survival through interaction with the host protein SSRP1,thereby creating a favorable environment for parasite growth.

关键词： Apoptosis SSRP1 TgPP2C Toxoplasma gondii

Intraoperative hemodynamic parameters of middle cerebral artery and other artery aneurysms utilizing transcranial Doppler ultrasonography

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Neural Regeneration Research 2010年第11期5卷 874-880页

作者： Jianjun Sun Shuo Wang Yuanli Zhao Dong Zhang Yoko Kato O isabelle liu O Jizong Zhao Department of Neurosurgery Third Hospital Peking University Beijing 100191 China Department of Neurosurgery Tiantan Hospital Affiliated to Capital Medical University Beijing 100050 China Department of Neurosurgery Fujita Health University Toyoake Aichil 470-1192 Japan Washington University in St Louis School of Medicine St Louis MO 63110 USA

BACKGROUND： Hemodynamic changes accompany the initiation, development and rupture of middle cerebral artery （MCA） aneurysms. The complexity of the intraaneurysmal hemodynamic factors has not been completely clarified by the indirect measures and methods used in previous studies. OBJECTIVE： To evaluate correlations of intraoperative hemodynamic factors to initiation and rupture of MCA aneurysms. DESIGN, TIME AND SETTING： A case-control study was performed at the Department of Neurosurgery, Tiantan Hospital Affiliated to Capital Medical University, China between March and October 2008. PARTICIPANTS： A total of 12 consecutive patients diagnosed with MCA aneurysms （MCA aneurysms group） and five patients without middle cerebral artery aneurysms （with aneurysms located at other arteries, control group） were enrolled at the Department of Neurosurgery, Tiantan Hospital Affiliated to Capital Medical University, China. METHODS： The proximal and distal arteries of MCA aneurysms were exposed visibly in the MCA aneurysm group. The M1 segment of MCA without the aneurysm and the aneurysm on other arteries were also exposed visibly in the control group. Hemodynamic indices were then measured using an intraoperative 16 MHz probe installed in a Multi-Dop TCD8X4 device. MAIN OUTCOME MEASURES： Mean （time-averaged velocity） difference, maximum mean, pulsatility index difference, maximum pulsatility index, resistance index difference, maximum resistance index; correlation of development and rupture of MCA aneurysms to intraoperative hemodynamic factors of the parent artery. RESULTS： A total of 12 patients underwent microsurgery for treatment to occlude 15 MCA aneurysms. Of the 15 MCA aneurysms, 12 were located at the bifurcation, two at the M1 segment and one at the M3 segment; eight of the aneurysms were unruptured and seven were ruptured. The whole indices with combination mean difference, maximum mean, and maximum pulsatility index of the aneurysms were important factors influencing t

关键词： aneurysms middle cerebral artery intraoperative hemodynamics impingement force rupture brain injury neural regeneration

Interleukin-33 drives hepatic fibrosis through activation of hepatic stellate cells

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Cellular & Molecular Immunology 2018年第4期15卷 388-398页

作者： Zhongming Tan Qianghui liu Runqiu Jiang Long Lv Siamak S Shoto isabelle Maillet Valerie Quesniaux Junwei Tang Wenjie Zhang Beicheng Sun Bernhard Ryffel Key Laboratory of Living Donor Liver Transplantation Department of Liver SurgeryNational Health and Family Planning CommissionThe First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuP.R.China Molecular Immunology and Embryology UMR 7355CNRSUniversity of OrleansOrléansFrance IIDMM University of Cape TownCape TownSouth Africa Department of General Surgery People’s Hospital of GaochunNanjingJiangsuP.R.China

Liver fibrosis is a consequence of chronic liver disease,causing morbidity and ***-33(IL-33)is a critical mediator of inflammation,which may be involved in the development of liver ***,we investigated the role of IL-33 in human patients and experimental bile-duct ligation(BDL)-induced fibrosis in *** report increased hepatic IL-33 expression in the murine BDL model of fibrosis and in surgical samples obtained from patients with liver *** injury,inflammatory cell infiltration and fibrosis were reduced in the absence of the IL-33/ST2 receptor,and the activation of hepatic stellate cells(HSCs)was decreased in ST2-deficient *** IL-33 activated HSCs isolated from C57BL/6 mice,leading to the expression of IL-6,TGF-β,α-SMA and collagen,which was abrogated in the absence of ST2 or by pharmacological inhibition of MAPK ***,administration of recombinant IL-33 significantly increased hepatic inflammation in sham-operated BL6 mice but did not enhance BDL-induced hepatic inflammation and *** conclusion,BDL-induced liver inflammation and fibrosis are dependent on ST2 signaling in HSCs,and therefore,the IL-33/ST2 pathway may be a potential therapeutic target in human patients with chronic hepatitis and liver fibrosis.

关键词： hepatic stellate cells IL-33 liver fibrosis ST2

Diabetic corneal neuropathy as a surrogate marker for diabetic peripheral neuropathy

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Neural Regeneration Research 2022年第10期17卷 2172-2178页

作者： Wei Zheng So Natalie Shi Qi Wong Hong Chang Tan Molly Tzu Yu Lin isabelle Xin Yu Lee Jodhbir S.Mehta Yu-Chi liu Yong Loo Lin School of Medicine National University of SingaporeSingaporeSingapore Singapore Eye Research Institute SingaporeSingapore Department of Endocrinology Singapore General HospitalSingaporeSingapore Department of Cornea and External Eye Disease Singapore National Eye CentreSingaporeSingapore Ophthalmology and Visual Sciences Academic Clinical Program Duke-NUS Medical SchoolSingaporeSingapore

Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropathy and diabetic peripheral neuropathy,*** peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies,clinical scoring,and skin ***,these diagnostic methods have limited sensitivity in detecting small-fiber disease,hence they do not accurately reflect the status of diabetic *** recently,analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral *** this review,we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy,elaborating on the foundational aspects of each:pathogenesis,clinical presentation,evaluation,and *** will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy,particularly early diabetic peripheral neuropathy;the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy;and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.

关键词： corneal nerve quantification corneal nerves diabetic cornea diabetic corneal neuropathy diabetic microvascular complications diabetic peripheral neuropathy in vivo confocal microscopy neurotrophic keratopathy ocular surface

Climate change and its association with the expansion of vectors and vector-borne diseases in the Hindu Kush Himalayan region:A systematic synthesis of the literature

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Advances in Climate Change Research 2021年第3期12卷 421-429页

作者： Meghnath DHIMAL isabelle Marie KRAMER Parbati PHUYAL Shyam Sundar BUDHATHOKI Juliane HARTKE Bodo AHRENS Ulrich KUCH David AGRONEBERG Santosh NEPAL Qi-Yong liu Cun-Rui HUANG Gueladio CISSE Kristie LEBI Doris KLINGELHOFER Ruth MULLER Nepal Health Research Council(NHRC) Kathmandu44600Nepal Global Institute for Interdisciplinary Studies(GIIS) Kathmandu44600Nepal Institute of Occupational Social and Environmental MedicineGoethe UniversityFrankfurt am Main60590Germany Institute for Atmospheric and Environmental Sciences(IAU) Goethe UniversityFrankfurt am Main60438Germany Department of Biomedical Sciences Institute of Environment and Sustainable DevelopmentUniversity of AntwerpAntwerp2000Belgium Department of Primary Care and Public Health School of Public HealthImperial College LondonLondonW2 IPGUnited Kingdom Department of Biomedical Sciences Institute of Tropical MedicineAntwerp2000Belgium International Centre for Integrated Mountain Development(ICIMOD) Kathmandu44600Nepal Department of Vector Biology and Control National Institute for Communicable Disease Control and PreventionChina CDCBeijing102206China WHO Collaborating Centre for Vector Surveillance and Management Beijing102206China Department of Health Policy&Management School of Public HealthSun Yat-sen UniversityGuangzhou510275China Department of Epidemiology and Public Health(EPH) Swiss Tropical and Public Health Institute(Swiss TPH)Basel4051Switzerland University of Basel Basel4001Switzerland Department of Global Health University of WashingtonSeattleWA98104USA

Observed weather and projected climate change suggest an increase in the transmission of vector-borne diseases(VBDs)in the Hindu Kush Himalayan(HKH)*** this study,we systematically explore the literature for empiric associations between the climate variables and specific VBDs and their vectors in the HKH *** conducted a systematic synthesis of the published literature on climate variables,VBDs and vectors in the HKH region until the 8th of December *** majority of studies show significant positive associations of VBDs with climatic factors,such as temperature,precipitation,relative humidity,*** systematic review allowed us to identify the most significant variables to be considered for evidence-based trend estimates of the effects of climate change on VBDs and their vectors in the HKH *** evidence-based trend was set into the context of climate change as well as the observed expansion of VBDs and disease vectors in the HKH *** geographic range of VBDs expanded into previously considered non-endemic areas of highlands(mountains)in the HKH region.B ased on scarce,but clear evidence of a positive relationship of most climate variables and VBDs and the observed climatic changes,we strongly recommend an expansion of vector control and surveillance programmes in areas of the HKH region that were previously considered to be non-endemic.

关键词： Chikungunya Dengue Filariasis High altitude Himalayas Leishmaniasis Mountain Mosquito Malaria Sandfly

黄葵胶囊治疗2型糖尿病肾脏病患者白蛋白尿疗效及安全性的临床研究

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中华糖尿病杂志 2023年第6期15卷 517-525页

作者：赵静 Tostivint isabelle 许陵冬黄继汉 Gambotti Laetitia Boffa Jean-Jacques 杨敏王玲孙铸兴陈晓岚 Liou-Schischmanoff Amélie Baumelou Alain 马腾卢国元李玲陈岱 Piéroni Laurence 刘炳凯秦笑何伟明王跃娟顾丰孙伟南京中医药大学附属医院肾内科南京210029 法国巴黎索邦大学附属比提耶-萨勒伯特医院肾内科巴黎75013 法国巴黎索邦大学附属比提耶-萨勒伯特医院中西医结合部巴黎75013 上海中医药大学药物临床研究中心上海201203 法国布洛涅-比扬古国家肿瘤研究所临床研究部布洛涅-比扬古92100 法国巴黎索邦大学附属德隆医院肾内科巴黎75020 常州市第一人民医院肾内科常州213004 徐州市第一人民医院肾内科徐州221002 无锡市人民医院肾内科无锡214023 南通大学附属医院肾内科南通226006 法国巴黎索邦大学附属比提耶-萨勒伯特医院药学部巴黎75013 泰州市中医院肾内科泰州225399 苏州大学附属第一医院肾内科苏州215006 东南大学附属中大医院内分泌科南京210009 常州市中医医院肾内科常州213004 法国巴黎索邦大学附属德隆医院荷尔蒙学生物化学部巴黎75020 中国药科大学基础医学与临床药学学院南京211199

目的探讨黄葵胶囊治疗2型糖尿病肾脏病患者白蛋白尿的疗效及安全性。方法为多中心、随机、双盲和平行对照试验。选取2017年5月至2021年3月在江苏省9家三甲医院(南京中医药大学附属医院、常州市第一人民医院、徐州市第一人民医院、无锡... 详细信息

目的探讨黄葵胶囊治疗2型糖尿病肾脏病患者白蛋白尿的疗效及安全性。方法为多中心、随机、双盲和平行对照试验。选取2017年5月至2021年3月在江苏省9家三甲医院(南京中医药大学附属医院、常州市第一人民医院、徐州市第一人民医院、无锡市人民医院、南通大学附属医院、泰州市中医院、苏州大学附属第一医院、东南大学附属中大医院、常州市中医医院)就诊的2型糖尿病肾脏病患者作为研究对象,采用分层区组随机的方法将患者分配到厄贝沙坦组[厄贝沙坦(150 mg/次,1次/d)+黄葵胶囊模拟剂(2.5 g/次,3次/d)]、黄葵胶囊组[黄葵胶囊(2.5 g/次,3次/d)+厄贝沙坦模拟剂(150 mg/次,1次/d)]和联合治疗组[厄贝沙坦(150 mg/次,1次/d)+黄葵胶囊(2.5 g/次,3次/d)]治疗,试验周期为24周。检测患者基线及治疗24周后尿肌酐及尿白蛋白,并计算尿白蛋白/肌酐比值(UACR),观察UACR较基线的变化值和变化率,记录患者不良事件、不良反应、严重不良事件、严重不良反应、导致退出的不良事件的发生情况并计算发生率。采用单因素方差分析、χ^(2)检验或Fisher精确概率法进行组间比较。结果共纳入413例2型糖尿病肾脏病患者。其中,厄贝沙坦组138例,黄葵胶囊组137例,联合治疗组138例。治疗24周后,3组患者UACR变化值分别为(-89.07±51.17)、(-146.06±45.52)和(-262.31±39.08)mg/g,黄葵胶囊组与厄贝沙坦组UACR变化值差异没有统计学意义(P=0.087),联合治疗组与厄贝沙坦组间差异有统计学意义(P0.05)。结论联合使用厄贝沙坦和黄葵胶囊可以进一步降低2型糖尿病肾脏病患者UACR水平,在控制2型糖尿病肾脏病患者白蛋白尿的治疗中具有较好的疗效和安全性。

关键词：糖尿病,2型糖尿病肾脏病白蛋白尿黄葵胶囊

操作系统对象语义模型(OSOSM)及形式化验证

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计算机研究与发展 2012年第12期49卷 2702-2712页

作者：钱振江刘苇黄皓南京大学软件新技术国家重点实验室南京210046 南京大学计算机科学与技术系南京210046

操作系统的复杂性使得其安全性问题日益突出.有不少的研究工作采用形式化的方式对现有的操作系统进行了正确性的验证,这些工作主要是采用程序形式逻辑验证代码级的功能实现性.从系统设计的角度,以高阶逻辑和类型论为基础,提出了操作系... 详细信息

操作系统的复杂性使得其安全性问题日益突出.有不少的研究工作采用形式化的方式对现有的操作系统进行了正确性的验证,这些工作主要是采用程序形式逻辑验证代码级的功能实现性.从系统设计的角度,以高阶逻辑和类型论为基础,提出了操作系统对象语义模型(OSOSM).OSOSM采用分层结构,包括基本功效层、实现层和优化层.OSOSM将操作系统中的行为主体和资源抽象为操作系统对象,建立操作系统的论域,利用以操作系统对象变元集合为定义域到论域的映射表示操作系统的状态,描述操作系统系统调用等行为的语义,使用逻辑系统的谓词公式表达操作系统的安全属性,给出如何验证操作系统在运行过程中保持安全策略和属性的形式化描述方法.以实现并经过形式化验证的可信操作系统(VTOS)为例,阐述OSOSM的语义正确性.使用isabelle定理证明工具验证设计和安全需求的一致性,以说明VTOS具有预期的安全属性.

关键词：操作系统对象语义模型形式化设计安全性验证 isabelle定理证明

HybridHP:一种轻型的内核完整性监控方案及其形式化验证

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计算机学报 2012年第7期35卷 1462-1474页

作者：钱振江刘苇黄皓南京大学软件新技术国家重点实验室南京210046 南京大学计算机科学与技术系南京210046 常熟理工学院计算机科学与工程学院江苏常熟215500

虽然传统的虚拟化监控方法可以在一定程度上保障操作系统安全.然而,虚拟监控器VMM中管理域Domain0的存在以及操作系统级的切换所带来的性能损失是很多具有大型应用的操作系统所不能接受的.注重硬件虚拟化技术的监控能力而摒弃其不必要... 详细信息

虽然传统的虚拟化监控方法可以在一定程度上保障操作系统安全.然而,虚拟监控器VMM中管理域Domain0的存在以及操作系统级的切换所带来的性能损失是很多具有大型应用的操作系统所不能接受的.注重硬件虚拟化技术的监控能力而摒弃其不必要的虚拟化能力,提出了一个新型的通用的虚拟化监控框架HybridHP,并实现其原型.HybridHP将管理域和虚拟机监控机制两者整合到被监控操作系统的地址空间,具有很好的获取被监控系统操作语义的能力.利用isabelle/HOL形式化辅助证明工具验证HybridHP的隔离性、安全性和监控能力.最后对HybridHP进行了攻击实验和性能评估,结果显示HybridHP提供了和传统的虚拟化监控方案相同的安全保障,并具有很好的系统性能.

关键词：硬件虚拟化内核完整性安全监控安全攻击 isabelle形式化验证