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| 1 | Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques显示文摘As of June 2020, Coronavirus Disease 2019(COVID-19) has killed an estimated 440 000 people worldwide, 74% of whom were aged ≥65 years,making age the most significant risk factor for death caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection. To examine the effect of age on death, we established a SARSCoV-2 infection model in Chinese rhesus macaques(Macaca mulatta) of varied ages. Results indicated that infected young macaques manifested impaired respiratory function, active viral replication, severe lung damage, and infiltration of CD11b^+ and CD8^+ cells in lungs at one-week post infection(wpi), but also recovered rapidly at 2 wpi. In contrast, aged macaques demonstrated delayed immune responses with a more severe cytokine storm, increased infiltration of CD11b^+ cells, and persistent infiltration of CD8^+ cells in the lungs at 2 wpi. In addition,peripheral blood T cells from aged macaques showed greater inflammation and chemotaxis, but weaker antiviral functions than that in cells from young macaques. Thus, the delayed but more severe cytokine storm and higher immune cell infiltration may explain the poorer prognosis of older aged patients suffering SARS-CoV-2 infection. | Tian-Zhang Song Hong-Yi Zheng Jian-Bao Han Lin Jin Xiang Yang Feng-Liang Liu Rong-Hua Luo Ren-Rong Tian Hou-Rong Cai Xiao-Li Feng Chao Liu Ming-Hua Li Yong-Tang Zheng | 2020 | Zoological Research2020，41，5： | 15 |
| 2 | 中国实验动物学科发展的关键问题与对策的思考显示文摘实验动物学是一门新兴交叉学科,它集成生物学、兽医学、生物工程、医学、药学、生物医学工程等学科的理论和方法,以实验动物和动物实验技术为研究对象,为相关学科发展提供系统性生物学材料和相关技术.实验动物学科产生的实验动物、动物模型、生物信息、动物实验技术、动物实验设备等,是生命科学、人类疾病、生物安全、药物研发、食品安全、航空航天、农业、环境等领域创新研究和发展的科技资源. | 秦川 | 2017 | 科学通报2017，62，30： | 13 |
| 3 | 食蟹猴急性酒精性脂肪肝脾胃湿热证模型的建立与评价初探显示文摘目的:建立急性酒精性脂肪肝脾胃湿热证食蟹猴模型,为酒精性脂肪肝的中医药现代研究提供研究工具。方法:将6只健康成年雄性食蟹猴按体质量随机分为正常组、模型组,每组3只,采用60d单纯自由饮酒建立急性酒精性脂肪肝病证结合食蟹猴模型。每日观察食蟹猴的外在宏观表征,制定中医证候积分标准,对每只食蟹猴进行中医证候综合评分。采用全自动生化分析仪检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆固醇(TC)、甘油三酯(TG)的含量,应用ELISA检测血清胃泌素(GAS)、胃动素(MTL)含量,肝脏B超及HE染色观察肝组织病理学变化,计算肝指数变化。结果:与正常组比较,模型组第60天时血清ALT、AST、TC、TG、GAS、MTL含量及肝指数均显著升高(P<0.05,P<0.01),肝脏B超、HE染色显示模型组肝组织出现弥漫性脂肪样病变,中医证候积分显示该模型为脾胃湿热证模型。结论:60d梯度饮酒可以成功建立急性酒精性脂肪肝脾胃湿热证食蟹猴模型,该模型符合人类酒精性脂肪肝病理特点和中医脾胃湿热证证候特点,是较为理想的酒精性脂肪肝脾胃湿热证模型。 | 梁丹 李晓红 唐耀平 唐海波 张丽峰 冷静 | 2021 | 中华中医药杂志2021，36，3： | 6 |
| 4 | A transgenic monkey model for the study of human brain evolution显示文摘Why humans have large brains with higher cognitive abilities is a question long asked by scientjsts.However,much remains unknown,especially the underlying genetic mechanisms.With the use of a transgenic mon key model,we showed that human-specific sequenee changes of a key brain development gene(Primary microcephaly 1,MCPH7)could result in detectable molecularand cognitive changes resembling human neoteny,a no table characteristic developed during human evolution.This study was published in National Science Review(Shi et al.,2019). | Lei Shi Bing Su | 2019 | Zoological Research2019，40，3： | 5 |
| 5 | The 3rd Symposium on Animal Models of Primates——The Application of Non-Human Primates to Basic Research and Translational Medicine显示文摘In order to understand the fundamental questions of the biology of life and to duplicate the pathogenesis of human diseases,animal models using different experimental animals,such as rodents,Drosophila,Caenorhabditis elegans,and zebrafish,have been established and used widely for | Yong-Gang Yao Yong-Bin Chen Bin Liang | 2015 | Journal of Genetics and Genomics2015，42，6： | 4 |
| 6 | Stem cell therapy for Parkinson’s disease using non-human primate models显示文摘Stem cell therapy (SCT) for Parkinson’s disease (PD) has received considerable attention in recent years. Non-human primate (NHP) models of PD have played an instrumental role in the safety and efficacy of emerging PD therapies and facilitated the translation of initiatives for human patients. NHP models of PD include primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, who are responsive to dopamine replacement therapies, similar to human PD patients. Extensive research in SCT has been conducted to better treat the progressive dopaminergic neurodegeneration that underlies PD. For effective application of SCT in PD, however, a number of basic parameters still need to be tested and optimized in NHP models, including preparation and storage of cells for engraftment, methods of transplantation, choice of target sites, and timelines for recovery. In this review, we discuss the current status of NHP models of PD in stem cell research. We also analyze the advances and remaining challenges for successful clinical translation of SCT for this persistent disease. | Zhen-Zhen Chen Yu-Yu Niu | 2019 | Zoological Research2019，40，5： | 4 |
| 7 | Age-associated changes in amyloid-β and formaldehyde concentrations in cerebrospinal fluid of rhesus monkeys显示文摘DEAR EDITOR,Rhesus monkeys(Macaca mulatta)are valuable experimental animals for studies on neurodegenerative diseases due to their evolutionarily close relationship to humans(Zhang et al.,2014).Rhesus monkeys also display similar hallmarks of aging and neurodegeneration as humans,including formation of senile plaques in the brain(Beckman et al.,2019;Paspalas et al.,2018). | Zhen-Hui Li Xia-Ping He Hao Li Rong-Qiao He Xin-Tian Hu | 2020 | Zoological Research2020，41，4： | 3 |
| 8 | 幼年期实验用食蟹猴血液学指标测定与比较显示文摘目的通过测定853只正常幼年期食蟹猴的血液学指标,统计并建立广东省内幼年期实验用食蟹猴各年龄段的血液学指标正常值参考范围。方法随机选取1~2周岁(1≤x<2)食蟹猴273只(雌性124只,雄性149只),2~3周岁(2≤x<3)食蟹猴307只(雌性244只,雄性63只),3~4周岁(3≤x<4)食蟹猴273只(雌性124只,雄性149只),检测其血液学指标,再按性别分亚组进行比较。结果建立了幼年期实验用食蟹猴各年龄段的血液学指标正常值参考范围;雌雄动物之间比较,1~2周岁动物血常规指标中,PLT等7项指标存在差异显著性(P<0.05或P<0.01);2~3周岁动物血常规指标中,RDW-SD等5项指标差异有显著性(P<0.05或P<0.01);3~4周岁动物血常规指标中,WBC等11项指标有显著性差异(P<0.05或P<0.01);其余无统计学意义。结论幼年期食蟹猴处于生长发育阶段,其血液学指标在不同年龄段存在较大差异,且不同性别间差异明显。本研究提供了正常食蟹猴幼年期不同年龄段的血液学背景数据,为其在生物医学领域的应用提供了可靠的参考。 | 何钢华 廖金娥 陈结文 黄庆宇 罗群 吴志恒 陈梅丽 卢丽 | 2019 | 中国比较医学杂志2019，29，10： | 2 |
| 9 | 间接酶联免疫吸附法测定血液中抗西尼罗河病毒单克隆抗体MIL94浓度及其应用显示文摘目的建立食蟹猴血清中抗西尼罗河病毒单抗MIL94的间接酶联免疫吸附(ELISA)定量测定法,并进行食蟹猴体内药动学初步研究。方法抗原包被量为每孔100 ng,酪蛋白封闭液于37℃孵育1 h,血清样品用PBS进行前处理,二抗按1∶10000稀释,3,3′,5,5′-四甲基联苯胺溶液室温显色10 min,硫酸终止反应。12只食蟹猴随机分为2组,每组6只,分别30 min内静脉推注MIL945和100 mg·kg^(-1),不同时间点(1 h~56 d)采血,分离血清,ELISA法测定血清中MIL94浓度。WinNonlin软件计算药动学参数,分析药动学特征。结果该方法的线性范围为0.25~32 mg·L^(-1),板内精密度1.18%~4.62%,板间精密度8.19%~10.20%。食蟹猴静注MIL945和100 mg·kg^(-1),半衰期分别为8±5和(8±5)d,清除率(Cl)分别为0.25±0.08和(0.26±0.009)mL·h^(-1)·kg^(-1),稳态表观分布容积分别为55±21和(74±19)mL·kg^(-1),药时曲线下面积(AUC)分别为951.2±393和(18030±6139)d·mg·L^(-1),AUC与剂量成正比,Cl不随剂量改变而改变。结论建立的间接酶联免疫吸附法的灵敏度、特异性、线性范围、精密度和稳定性等均满足临床前药动学研究需求。初步获得了MIL94在5~100 mg·kg^(-1)的静注剂量范围内,食蟹猴体内的线性药动学特征,为MIL94的研发提供支持。 | 相亚楠 王灵超 高尤 罗龙龙 张文鹏 庄笑梅 | 2021 | 中国药理学与毒理学杂志2021，35，3： | 2 |
| 10 | 食蟹猴急性心肌梗死模型的建立及护理显示文摘目的通过2014~2018年在浙江大学医学院附属第二医院大动物基地(大动物基地)建立的174例食蟹猴急性心肌梗死(AMI)模型的分析,归纳了食蟹猴标准化的AMI建模过程及造模后食蟹猴的护理方法。方法选择健康成年雄性食蟹猴在左冠状动脉前降支(LAD)第一对角支和第二对角支之间进行结扎,术中维持生命体征及发生室颤(VF)时积极抢救,术后控制感染、保持体温、维持饮食等措施保证食蟹猴的生存。结果术中及术后1 d、2 d和3 d死亡率分别是2.3%、8.0%、2.3%和1.7%。结论在LAD第一对角支和第二对角支之间进行结扎可以建立理想的食蟹猴AMI模型,通过术中和术后合理护理,降低了AMI模型构建后食蟹猴的死亡率。 | 王成舟 | 2019 | 实验动物与比较医学2019，39，4： | 2 |
| 11 | 间接ELISA法检测大鼠血清中抗埃博拉病毒双特异性抗体MBS77E浓度及大鼠体内药代动力学研究显示文摘目的建立并验证间接ELISA法定量检测大鼠血清中抗埃博拉病毒双特异性抗体MBS77E浓度,并进行大鼠体内药代动力学研究。方法15只大鼠随机分为3组,每组5只,分别静脉注射不同剂量(0.5、10.0和50.0 mg·kg^(-1))的MBS77E,不同时间点采血,分离血清,ELISA法测定血清中MBS77E浓度。WinNonlin软件计算药代动力学参数,分析药代动力学特征。结果在0.098~12.50μg·mL^(-1),MBS77E质量浓度的对数值与吸光值呈S形曲线;板内精密度在5.3%~11.3%;板间精密度在3.0%~11.1%;该方法不受基质干扰,无明显钩状效应,稀释线性、选择性、平行性满足要求,样品冻存至28 d稳定。大鼠静脉注射0.5、10.0和50.0 mg·kg^(-1)的MBS77E后,半衰期分别为(12.82±1.02)、(8.21±3.82)和(8.00±1.02)d,清除率分别为(8.61±0.56)、(8.53±1.69)和(6.60±0.78)mL/(d·kg),表观分布容积分别为(160.28±5.89)、(91.46±13.46)和(93.01±4.15)mL·kg^(-1),药时曲线下面积(AUC)分别为(56.24±3.14)、(1149.07±266.78)和(7504.36±834.36)d·μg·mL^(-1),AUC与剂量成正比,清除率随剂量升高有下降趋势。结论该方法符合生物技术药物临床前药代动力学研究指导原则的要求,且获得了MBS77E在大鼠体内的药代动力学特征,为MBS77E的临床研究提供了支持。 | 相亚楠 高尤 冯健男 张文鹏 庄笑梅 | 2021 | 中南药学2021，19，4： | 1 |
| 12 | The RNA editome of Macaca mulatta and functional characterization of RNA editing in mitochondria显示文摘RNA editing was first discovered in mitochondrial RNA molecular. However, whether adenosine-toinosine(A-to-I) RNA editing has functions in nuclear genes involved in mitochondria remains elusive.Here, we retrieved 707,246 A-to-I RNA editing sites in Macaca mulatta leveraging massive transcriptomes of 30 different tissues and genomes of nine tissues, together with the reported data, and found that A-to-I RNA editing occurred frequently in nuclear genes that have functions in mitochondria. The mitochondrial structure, the level of ATP production, and the expression of some key genes involved in mitochondrial function were dysregulated after knocking down the expression of ADAR1 and ADAR2, the key genes encoding the enzyme responsible for RNA editing. When investigating dynamic changes of RNA editing during brain development, an amino-acid-changing RNA editing site(I234/V) in MFN1, a mediator of mitochondrial fusion, was identified to be significantly correlated with age, and could influence the function of MFN1. When studying transcriptomes of brain disorder, we found that dysregulated RNA editing sites in autism were also enriched within genes having mitochondrial functions. These data indicated that RNA editing had a significant function in mitochondria via their influence on nuclear genes. | Ling-Qun Ye Hui Zhao He-JiangZhou Xiao-Die Ren Lin-Lin Liu Newton O.Otecko Zheng-boWang Min-Min Yang Lin Zeng Xin-Tian Hu Yong-Gang Yao Ya-Ping Zhang Dong-Dong Wu | 2017 | Science Bulletin2017，62，12： | 1 |
| 13 | 间接ELISA法测定猴血清中埃博拉病毒单克隆抗体MBS77E及药动学研究显示文摘目的:建立食蟹猴血清中抗埃博拉病毒单克隆抗体MBS77E的间接酶联免疫吸附(ELISA)定量测定法,并进行食蟹猴体内药动学研究。方法:建立优化一种定量检测食蟹猴血清中抗埃博拉病毒单克隆抗体MBS77E浓度的间接ELISA法,并进行全面验证。4只食蟹猴分为2组,每组2只,分别静脉推注不同剂量的MBS77E(5和100 mg·kg^(-1)),不同时间点采血,分离血清,采用ELISA法测定MBS77E浓度。使用WinNonlin软件计算药动学参数,分析药动学特征。结果:该方法的线性范围为0.098~12.5μg·mL^(-1),板内精密度为3.5%~9.9%,板间精密度为7.4%~11.8%。食蟹猴静注5和100 mg·kg^(-1)的MBS77E后,半衰期分别为(8.88±5.24)和(6.38±2.57)d,清除率分别为(7.55±1.48)和(6.22±0.99)mL·h^(-1)·kg^(-1),表观分布容积分别为(91.18±38.16)和(55.44±14.01)mL·kg^(-1),药时曲线下面积(AUC)分别为(631.58±76.75)和(16004.13±2230.73)μg·d·mL^(-1),AUC与剂量成正比,清除率不随剂量改变而改变。结论:建立的间接ELISA法测定猴血清中MBS77E浓度在特异性、线性范围、精密度和稳定性等方面,满足临床前药动学研究需求,初步获得了MBS77E在食蟹猴中的药动学特征。本研究为MBS77E的临床前及临床药动学研究提供了支持。 | 相亚楠 高尤 罗龙龙 张文鹏 庄笑梅 | 2021 | 中国新药杂志2021，30，12： | 1 |
| 14 | 食蟹猴的麻醉及麻醉前用药显示文摘食蟹猴是与人类最为接近的物种之一,在生理学、解剖学、免疫学以及神经学等方面有很高的相似度,在生物医学研究领域也是比较理想的实验动物,利用其建立的动物模型被广泛用于研究人类疾病,如在传染病、心血管疾病、内分泌疾病、生殖疾病、神经疾病及眼疾病等方面,对比欧美发达国家,中国具有相当丰富的灵长类动物资源提供国内外应用[1]。 | 蔡勇强 | 2021 | 浙江畜牧兽医2021，46，5： | 0 |
| 15 | Embryo-Engineered Nonhuman Primate Models: Progress and Gap to Translational Medicine显示文摘Animal models of human diseases are vital in better understanding the mechanism of pathogenesis and essential for evaluating and validating potential therapeutic interventions.As close relatives of humans,nonhuman primates(NHPs)play an increasingly indispensable role in advancing translational medicine research.In this review,we summarized the progress of NHP models generated by embryo engineering,analyzed their unique advantages in mimicking clinical patients,and discussed the remaining gap between basic research of NHP models to translational medicine. | Mei Huang Jiao Yang Peng Li Yongchang Chen | 2022 | Research2022，，1： | 0 |
| 16 | Potential use of actigraphy to measure sleep in monkeys: comparison with behavioral analysis from videography显示文摘DEAR EDITOR,Since the epoch-making observations of circadian rhythm in Mimosaceae plants,sleep has been investigated for centuries(de Mairan,1729;Du Monceau,1758).As a natural and reversible state,sleep is marked by reduced responsiveness to external stimuli,relative inactivity,and loss of consciousness.Although reduced responsiveness could potentially introduce significant danger to survival,nearly all animals in nature sleep. | Dong-Dong Qin Shu-Fei Feng Fei-Yu Zhang Na Wang Wen-Jie Sun Yin Zhou Teng-Fang Xiong Xian-Lai Xu Xiao-Ting Yang Xiang Zhang Xue Zhu Xin-Tian Hu Lei Xiong Yun Liu Yong-Chang Chen | 2020 | Zoological Research2020，41，4： | 0 |
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