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The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

Neural Regeneration Research 2025年第2期20卷 402-415页

作者： Xiaorong Zhang Zhiying Chen Yinyi Xiong Qin zhou ling-Qiang Zhu Dan Liu Department of Pathology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Jiujiang Clinical Precision Medicine Research Center JiujiangJiangxi ProvinceChina Center for Cognitive Science and Transdisciplinary Studies Jiujiang UniversityJiangxi ProvinceChina Department of Neurology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Department of Rehabilitation Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic ***,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia *** in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive *** oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous ***,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular *** review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular ***,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

关键词： endoplasmic reticulum stress endothelial nitric oxide synthase gene therapy nitric oxide NO-sGC-cGMP pathway synaptic dysfunction vascular dementia

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Single-cell analysis of angiotensin-converting enzyme II expression in human kidneys and bladders reveals a potential route of 2019 novel coronavirus infection

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Chinese Medical Journal 2021年第8期134卷 935-943页

作者： Wei Lin Jue Fan Long-Fei Hu Yan Zhang Joshua DOoi Ting Meng Peng Jin Xiang Ding Long-Kai Peng Lei Song Rong Tang zhou Xiao Xiang Ao Xiang-Cheng Xiao qiao-ling zhou Ping Xiao Yong Zhong Department of Pathology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Bioinformatics and Data Science Singleron BiotechnologiesNanjingJiangsu 210032China Centre for Inflammatory Diseases Monash University Department of MedicineMonash Medical CentreClaytonVIC 3168Australia Department of Nephrology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Organ Transplantation Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Kidney Transplantation The Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China

Background::Since 2019,a novel coronavirus named 2019 novel coronavirus(2019-nCoV)has emerged *** from fever and respiratory complications,acute kidney injury has been observed in a few patients with coronavirus disease ***,according to recent findings,the virus has been detected in ***-converting enzyme II(ACE2)has been proposed to serve as the receptor for the entry of 2019-nCoV,which is the same as that for the severe acute respiratory *** study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary ***::We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and *** Pearson correlation coefficients between ACE2 and all other genes were first ***,genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ***::Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule(PT)cells of the ***2 expression was found in 5.12%,5.80%,and 14.38%of the proximal convoluted tubule cells,PT cells,and proximal straight tubule cells,respectively,in three published kidney cell atlas *** addition,ACE2 expression was also confirmed in 12.05%,6.80%,and 10.20%of cells of the proximal convoluted tubule,PT,and proximal straight tubule,respectively,in our own two healthy kidney *** the analysis of public data from three bladder samples,ACE2 expression was low but detectable in bladder epithelial *** 0.25%and 1.28%of intermediate cells and umbrella cells,respectively,had ACE2 ***::This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.

关键词： 2019-nCoV Acute kidney injury Angiotensin-converting enzyme 2 Bladder COVID-19 Kidney RNA sequence analysis Single-cell analysis

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The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease

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Neural Regeneration Research 2025年第8期20卷 2361-2372页

作者： Shengyang zhou Ting Li Wei Zhang Jian Wu Hui Hong Wei Quan Xinyu qiao Chun Cui Chenmeng qiao Weijiang Zhao Yanqin Shen Laboratory of Neurodegenerative and Neuroinjury Diseases Wuxi Medicine SchoolJiangnan UniversityWuxiJiangsu ProvinceChina

Interferon regulatory factor 7 plays a crucial role in the innate immune ***,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains *** we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial *** the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 *** addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and *** together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

关键词： cyclic guanosine monophosphate adenosine monophosphate synthase H151 interferon regulatory factor 7 M1 phenotype neurodegenerative disease neuroinflammation Parkinson’s disease RU521 STING type I interferon

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葛根素对子宫内膜异位症细胞恶性行为调控机制研究

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中西医结合学报 2009年第1期7卷 41-47页

作者：俞超芹俞瑾韩洁周巧玲沈慰第二军医大学长海医院中医科上海200433 复旦大学妇产科医院中西医结合科上海200011 第二军医大学长征医院中医科上海200003

目的:观察葛根素对子宫内膜异位症(endometriosis,EM)血管形成的影响以及葛根素对EM肿瘤相关基因的调控作用。方法:利用子宫内膜细胞原代培养技术、鸡胚绒毛尿囊膜(chicken chorioallantoic membrane,CAM)模型、基因芯片等方法,了解EM... 详细信息

目的:观察葛根素对子宫内膜异位症(endometriosis,EM)血管形成的影响以及葛根素对EM肿瘤相关基因的调控作用。方法:利用子宫内膜细胞原代培养技术、鸡胚绒毛尿囊膜(chicken chorioallantoic membrane,CAM)模型、基因芯片等方法,了解EM肿瘤相关基因表达的情况,观察葛根素对EM血管生成、肿瘤相关基因的调控作用。结果:葛根素可明显抑制种植内膜组织囊泡及周边血管形成,其血管阳性面积显著小于模型组(P<0.05)。基因芯片结果显示,增殖期EM在位内膜组织较之正常在位内膜组织、EM异位内膜组织较之EM在位内膜组织,在癌基因,抑癌基因,细胞黏附、侵袭、转移、血管生成相关基因及细胞凋亡相关基因表达方面有明显不同。100μmol/L葛根素可明显上调EM在位基质细胞凋亡基因BAD、BAX、CASP8、CASP9和TNFRSF6表达,并增强细胞周期依赖性蛋白激酶抑制因子CDKN1B、CDKN2A及IFNA1、IFNB1基因表达;减少癌基因FOS、CHEK2、SRC和黏附侵袭基因ITGB5、MMP9及生长、转录因子基因PDGFA、NFKBIA表达。结论:葛根素能够抑制异位灶新生血管的形成,减少异位灶的血液供应;通过调整EM癌基因、抑癌基因、细胞周期相关因子基因表达,并通过影响凋亡相关基因的表达,促进细胞凋亡,从而改变EM内膜细胞类似肿瘤细胞的恶性行为。

关键词：子宫内膜异位症葛根素鸡胚绒毛尿囊膜模型基因芯片肿瘤相关基因

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Induced pluripotent stem cell-related approaches to generate dopaminergic neurons for Parkinson's disease

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Neural Regeneration Research 2025年第11期20卷 3193-3206页

作者： ling-Xiao Yi Hui Ren Woon Genevieve Saw Li Zeng Eng King Tan Zhi Dong zhou National Neuroscience Institute Singapore Nanyang Technology University Singapore Department of Neurology Singapore General HospitalSingapore Signature Research Program in Neuroscience and Behavioral Disorders Duke-NUS Medical SchoolSingapore

The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative *** the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and *** induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease *** current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem *** benefits of induced pluripotent stem cell-based research are *** dopaminergic neuron differentiation protocols from induced pluripotent stem cells are *** emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are ***,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.

关键词： dopaminergic neurons induced pluripotent stem cells Parkinson's disease stem cell approaches

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抗逆转录病毒药物治疗妊娠合并艾滋病的安全性研究进展

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中国临床药理学杂志 2017年第8期33卷 764-767页

作者：李琳黄桦王晶晶姚勤郑巧玲周琼张峻昆明医科大学第一附属医院临床药学科昆明650032

抗逆转录病毒药物是推荐用于感染人类免疫缺陷病毒1型(HIV-1)的孕妇或用于预防母婴垂直传播的一线药物,在全球妊娠合并艾滋病的妇女治疗中是一个重要的组成部分。本文主要对抗逆转录病毒药物在妊娠合并艾滋病患者中应用的安全性进行综述。

关键词：抗逆转录病毒药物妊娠艾滋病母婴传播

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Efficacy and safety of Shenyankangfu Tablet,a Chinese patent medicine,for primary glomerulonephritis:A multicenter randomized controlled trial

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Journal of Integrative Medicine 2021年第2期19卷 111-119页

作者： Jie Wu Shu-wei Duan Hong-tao Yang Yue-yi Deng Wei Li Ya-ni He Zhao-hui Ni Yong-li Zhan Shan Lin Zhi-yong Guo Jun Zhu Jing-ai Fang Xu-sheng Liu Li-hua Wang Rong Wang Nian-song Wang Xiao-hong Cheng Li-qun He Ping Luo Shi-ren Sun Ji-feng Sun Ai-ping Yin Geng-ru Jiang Hong-yu Chen Wen-hu Liu Hong-li Lin Meng Liang Lu Ma Ming Chen Li-qun Song Jian Chen Qing Zhu Chang-ying Xing Yun Li Ji-ning Gao Rong-shan Li Ying Li Hao Zhang Ying Lu qiao-ling zhou Jun-zhou Fu Qiang He Guang-yan Cai Xiang-mei Chen Department of Nephrology Chinese People’s Liberation Army General HospitalChinese People’s Liberation Army Institute of NephrologyState Key Laboratory of Kidney Diseases(2011DAV00088)National Clinical Research Center for Kidney DiseasesBeijing 100853China Department of Nephrology First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300192China Department of Nephrology Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Department of Nephrology Shandong University of Traditional Chinese Medicine Affiliated HospitalJinan 250011.Shandong ProvinceChina Department of Nephrology Daping HospitalArmy Medical UniversityChongqing 400042China Department of Nephrology Renji HospitalShanghai Jiao Tong UniversityShanghai 200127China Department of Nephrology Guang’anmen HospitalChina Academy of Traditional Chinese Medical SciencesBeijing 100053China Department of Nephrology Tianjin Medical University General HospitalTianjin 300052China Department of Nephrology Changhai Hospital of ShanghaiNaval Medical UniversityShanghai 200433China Department of Nephrology West China HospitalChengdu 610083Sichuan ProvinceChina Department of Nephrology First Affiliated Hospital of Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina Department of Nephrology Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510120Guangdong ProvinceChina Department of Nephrology Shanxi Medical University Second Affiliated HospitalTaiyuan 030001Shanxi ProvinceChina Department of Nephrology Shandong Provincial HospitalJinan 250021Shandong ProvinceChina Department of Nephrology and Rheumatology Affiliated Sixth People’s HospitalShanghai Jiao Tong UniversityShanghai 200233China Department of Nephrology Shaanxi Traditional Chinese Medicine HospitalXi'an 710003Shaanxi ProvinceChina Department of Nephrology Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 200021China Department of Nephrology Jilin University Se

Background:Shenyankangfu Tablet(SYKFT)is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney ***:This trial compared the efficacy and safety of SYKFT,for the control of proteinuria in primary glomerulonephritis patients,against the standard drug,losartan ***,setting,participants and intervention:This was a multicenter,double-blind,randomized,controlled clinical *** glomerulonephritis patients,aged 18-70 years,with blood pressure≤140/90 mmHg,estimated glomerular filtration rate(eGFR)>45 mL/min per 1.73 ㎡,and 24-hour proteinuria level of 0.5-3.0 g,were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups:SYKFT,losartan potassium 50 mg or 100 mg,SYKFT plus losartan potassium 50 mg or 100 *** outcome measu res:The primary outcome was change in the 24-hour proteinuria level,after 48 weeks of ***:A total of 735 participants were *** percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78%±2.56%(P=0.006)more than that in the losartan 50 mg group,which was 0.51%±2.54%(P=1.000)less than that in the losartan 100 mg *** with the losartan potassium 50 mg group,the SYKFT plus losartan potassium 50 mg group had a 13.39%±2.49%(P<0.001)greater reduction in urine protein *** with the losartan potassium 100 mg group,the SYKFT plus losartan potassium 100 mg group had a 9.77%±2.52%(P=0.001)greater reduction in urine *** a superiority threshold of 15%,neither was statistically ***,serum creatinine and serum albumin from the baseline did not change statistically *** average change in TCM syndrome score between the patients who took SYKFT(-3.00[-6.00,-2.00])and who did not take SYKFT(-2.00[-5.00,0])was statistically significant(P=0.003).No obvious adverse reactions were observed in any ***:SYKFT decreased the proteinur

关键词： Herbal medicine,Chinese Shenyankangfu Tablet Primary glomerulonephritis Randomized controlled trial Double blind Double dummy

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内异方药物血清对子宫内膜异位症血管生成的影响

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中西医结合学报 2012年第7期10卷 800-806页

作者：徐玲周巧玲韩洁张丹英董惠娟蔡在龙俞超芹翟东霞第二军医大学长海医院中医科上海200433 第二军医大学长海医院实验中心上海200433

目的:比较子宫内膜异位症(endometriosis,EM)在位、异位内膜组织与对照在位内膜组织的血管生成能力及血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达水平,并评价中药内异方药物血清对其的影响。方法:采用鸡胚尿囊膜(... 详细信息

目的:比较子宫内膜异位症(endometriosis,EM)在位、异位内膜组织与对照在位内膜组织的血管生成能力及血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达水平,并评价中药内异方药物血清对其的影响。方法:采用鸡胚尿囊膜(chick chorioallantoic membrane,CAM)上子宫内膜组织种植的方法建立EM模型。Sprague-Dawley大鼠分别灌胃生理盐水、达那唑和内异方制备对照血清和药物血清。将CAM模型分别用空白血清、达那唑药物血清和内异方药物血清干预后,测量种植灶面积和阳性血管面积,计算阳性血管面积百分比;免疫组织化学EnVision法检测各组种植组织中VEGF的表达。结果:EM患者的在位、异位内膜组织种植于CAM后,种植灶面积与对照在位内膜组比较差异无统计学意义(P>0.05),但EM异位内膜种植灶周围形成的血管面积显著高于在位内膜种植后(P0.05)。EM在位、异位内膜组种植灶中VEGF的阳性表达显著高于对照在位内膜组(P0.05)。结论:EM在位、异位内膜组织中VEGF的表达水平明显增高,异位内膜组织血管形成能力显著增强。内异方药物血清可显著降低EM在位和异位内膜组织中VEGF的表达,抑制种植灶新生血管网的形成,减少异位灶局部血供,从而抑制异位内膜组织的生长。与达那唑作用相比,中药内异方在抑制和治疗EM上有相似的作用,但在抑制异位内膜组织VEGF的表达方面,中药内异方作用更佳。

关键词：子宫内膜异位症鸡胚尿囊膜血管内皮生长因子中草药血管生成抑制剂

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Effective ensemble learning approach for SST field prediction using attention-based PredRNN

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Frontiers of Computer Science 2023年第1期17卷 143-155页

作者： Baiyou qiao Zhongqiang WU ling MA Yicheng zhou Yunjiao SUN School of Computer Science and Engineering Northeastern UniversityShenyang 110169China Key Laboratory of Intelligent Computing in Medical Image Ministry of EducationNortheastern UniversityShenyang 110169China

Accurate prediction of sea surface temperature (SST) is extremely important for forecasting oceanic environmental events and for ocean studies. However, the existing SST prediction methods do not consider the seasonal periodicity and abnormal fluctuation characteristics of SST or the importance of historical SST data from different times;thus, these methods suffer from low prediction accuracy. To solve this problem, we comprehensively consider the effects of seasonal periodicity and abnormal fluctuation characteristics of SST data, as well as the influence of historical data in different periods, on prediction accuracy. We propose a novel ensemble learning approach that combines the Predictive Recurrent Neural Network(PredRNN) network and an attention mechanism for effective SST field prediction. In this approach, the XGBoost model is used to learn the long-period fluctuation law of SST and to extract seasonal periodic features from SST data. The exponential smoothing method is used to mitigate the impact of severely abnormal SST fluctuations and extract the a priori features of SST data. The outputs of the two aforementioned models and the original SST data are stacked and used as inputs for the next model, the PredRNN network. PredRNN is the most recently developed spatiotemporal deep learning network, which simulates both spatial and temporal representations and is capable of transferring memory across layers and time steps. Therefore, we used it to extract the spatiotemporal correlations of SST data and predict future SSTs. Finally, an attention mechanism is added to capture the importance of different historical SST data, weigh the output of each step of the PredRNN network, and improve the prediction accuracy. The experimental results on two ocean datasets confirm that the proposed approach achieves higher training efficiency and prediction accuracy than the existing SST field prediction approaches do.

关键词： SST prediction ensemble learning XGBoost PredRNN attention mechanism

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仓鼠胰腺癌细胞株移植性肝癌模型的建立及其生物学特性

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世界华人消化杂志 2009年第18期17卷 1827-1831页

作者：毛庭枝周巧灵梁荣感戴支凯罗伟生肖胜军徐庆桂林医学院组织胚胎学教研室广西壮族自治区桂林市541004 桂林医学院药理学教研室广西壮族自治区桂林市541004 桂林医学院附属医院消化内科广西壮族自治区桂林市541004 桂林医学院病理学教研室广西壮族自治区桂林市541004

目的:建立仓鼠胰腺癌细胞株(pGHAM-1)移植性肝癌模型,并研究其生物学特性.方法:将pGHAM-1培养后配成4×1010/L,取0.5mL接种于仓鼠皮下,成瘤后,接种于仓鼠肝脏.分别于第20、30、40天用B超仪检测肝脏肿瘤大小.于接种后第40天处死动物,观... 详细信息

目的:建立仓鼠胰腺癌细胞株(pGHAM-1)移植性肝癌模型,并研究其生物学特性.方法:将pGHAM-1培养后配成4×1010/L,取0.5mL接种于仓鼠皮下,成瘤后,接种于仓鼠肝脏.分别于第20、30、40天用B超仪检测肝脏肿瘤大小.于接种后第40天处死动物,观察肿瘤的生长、转移及腹水量.解剖取出肝脏,用游标卡尺测量肿瘤大小,切开肝脏直接观察肿瘤,再进行HE染色的组织病理学检查,免疫组织化学检测血管内皮细胞生长因子(VEGF)及肿瘤转移相关蛋白(nm23-H1)的表达.结果:pGHAM-1种植性肝癌模型成功率达100%.B超仪检测仓鼠肝脏,第20、30、40天肿瘤体积分别为84.1±21.9mm3,413.7±208.4mm3,2187.3±1882.8mm3,与10d前者相比,有非常显著性差异(P0.05).部分仓鼠可见血性腹水;肝内未见肿瘤卫星结节;HE染色组织病理学检查为低分化胰腺癌;免疫组织化学检测结果显示VEGF及nm23-H1蛋白低表达.结论:pGHAM-1种植性肝癌模型建立方法简便,易复制,是理想的肝癌研究模型.

关键词： pGHAM-1 仓鼠肝癌模型胰腺癌细胞株

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