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Anti-neoplastic effects of topoisomerase inhibitors in canine mammary carcinoma, melanoma, and osteosarcoma cell lines. 拓扑异构酶抑制剂在犬乳腺癌、黑色素瘤和骨肉瘤细胞系中的抗肿瘤作用。
Pub Date : 2017-02-01 DOI: 10.14943/JJVR.65.1.17
S. Ong, Hiroki Yamamoto, K. Saeki, Yuiko Tanaka, R. Yoshitake, R. Nishimura, T. Nakagawa
Numerous topoisomerase inhibitors with proven efficacy have been used extensively to treat various human neoplasms. However, among these, only doxorubicin has been used and studied extensively in veterinary oncology. The current study was performed to evaluate the responsiveness of canine osteosarcoma (cOSA), mammary gland tumour (cMGT), and malignant melanoma (cMM) cell lines to several topoisomerase inhibitors. In addition, the correlation between the sensitivity to treatment and multi-drug resistant (MDR) factors was investigated. cOSA cell lines exhibited higher sensitivity than cMGT and cMM cell lines to all the topoisomerase inhibitors tested in vitro; this was associated with the levels of multi-drug resistance protein 1 (MDR1) gene expression in the cOSA cell lines. Treatment of cOSA (HMPOS) and cMGT cell line (CHMp) xenograft mouse models with etoposide markedly delayed tumour progression in HMPOS xenografts, but failed to elicit lasting anti-tumour effects on CHMp xenograft mice. The present findings suggest that MDR1 represents a molecular signature for prediction of treatment efficacy of topoisomerase inhibitors, especially that of etoposide, which may be a clinically useful anti-tumour agent for cOSA; however, further study is necessary to refine the treatment protocol.
许多拓扑异构酶抑制剂已被证实有效,广泛用于治疗各种人类肿瘤。然而,其中只有阿霉素在兽医肿瘤学中得到了广泛的应用和研究。目前的研究是为了评估犬骨肉瘤(cOSA)、乳腺肿瘤(cMGT)和恶性黑色素瘤(cMM)细胞系对几种拓扑异构酶抑制剂的反应性。此外,还探讨了多药耐药(MDR)因素与治疗敏感性的关系。cOSA细胞株对所有拓扑异构酶抑制剂的敏感性均高于cMGT和cMM细胞株;这与cOSA细胞系中多药耐药蛋白1 (MDR1)基因表达水平有关。用依托泊苷治疗cOSA (HMPOS)和cMGT细胞系(CHMp)异种移植小鼠模型,显著延缓了HMPOS异种移植小鼠的肿瘤进展,但未能对CHMp异种移植小鼠产生持久的抗肿瘤作用。目前的研究结果表明,MDR1代表了预测拓扑异构酶抑制剂治疗效果的分子特征,特别是依托泊苷,它可能是临床有用的cOSA抗肿瘤药物;然而,需要进一步的研究来完善治疗方案。
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引用次数: 5
Canine osteosarcoma cell lines contain stem-like cancer cells: biological and pharmacological characterization. 犬骨肉瘤细胞系含有干细胞样癌细胞:生物学和药理学特征。
Pub Date : 2016-05-01 DOI: 10.14943/JJVR.64.2.101
Monica Gatti, Roberto Wurth, G. Vito, A. Pattarozzi, C. Campanella, S. Thellung, L. Maniscalco, R. De Maria, V. Villa, A. Corsaro, M. Nizzari, A. Bajetto, A. Ratto, A. Ferrari, F. Barbieri, T. Florio
Cancer stem cells (CSCs) represent a small subpopulation of cells responsible for tumor formation and progression, drug resistance, tumor recurrence and metastasization. CSCs have been identified in many human tumors including osteosarcoma (OSA). CSC distinctive properties are the expression of stem cell markers, sustained growth, self-renewal and tumorigenicity. Here we report the isolation of stem-like cells from two canine OSA cultures, characterized by self-renewal, evaluated by sphere formation ability, differential marker expression, and in vitro proliferation when cultured in a medium containing EGF and bFGF. Current therapies for OSA increased survival time, but prognosis remains poor, due to the development of drug resistance and metastases. Chemotherapy shrinks the tumor mass but CSCs remain unaffected, leading to tumor recurrence. Metformin, a drug for type 2 diabetes, has been shown to possess antitumor properties affecting CSC survival in different human and animal cancers. Here we show that metformin has a significant antiproliferative effect on canine OSA stem-like cells, validating this in vitro model for further pre-clinical drug evaluations. In conclusion, our results demonstrate the feasibility of obtaining CSC-enriched cultures from primary canine OSA cells as a promising model for biological and pharmacological studies of canine and human OSAs.
肿瘤干细胞(Cancer stem cells, CSCs)是一小部分参与肿瘤形成和进展、耐药、肿瘤复发和转移的细胞。在包括骨肉瘤(OSA)在内的许多人类肿瘤中已经发现了CSCs。CSC的特点是干细胞标志物的表达、持续生长、自我更新和致瘤性。在这里,我们报道了从两种犬OSA培养物中分离出的干细胞,其特征是自我更新,通过球体形成能力、差异标记表达和在含有EGF和bFGF的培养基中培养时的体外增殖来评估。目前的治疗方法增加了OSA的生存时间,但由于耐药性和转移的发展,预后仍然很差。化疗缩小肿瘤肿块,但CSCs不受影响,导致肿瘤复发。二甲双胍是一种治疗2型糖尿病的药物,已被证明具有影响不同人类和动物癌症CSC存活的抗肿瘤特性。在这里,我们发现二甲双胍对犬OSA干细胞有显著的抗增殖作用,验证了这一体外模型,以进一步进行临床前药物评估。总之,我们的研究结果表明,从原代犬OSA细胞中获得富含csc的培养物作为犬和人OSA生物学和药理学研究的有希望的模型是可行的。
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引用次数: 4
An unusual case of thoracic ectopia cordis in a Toggenburg Goat and its three-dimensional images constructed with X-ray computed tomography. 一个不寻常的病例胸廓异位在Toggenburg山羊和它的三维图像构建与x线计算机断层。
Pub Date : 2016-05-01 DOI: 10.14943/JJVR.64.2.165
J. Lai, Jui-Te Wu, Wei-Cheng Yang, Ming Chao, H. Nagahata
A two-day-old female Toggenburg goat with thoracic ectopia cordis (EC) was diagnosed via radiography and computed tomography. The goat was born with EC, defects of the sternum and a supra-umbilical abdominal wall, but without the presence of Cantrell's syndrome. Necropsy and histopathological findings indicated the affected kid had malformation of the heart with an enlarged left ventricle. The findings showed the heart (9 x 5 x 5 cm) stayed outside the thorax, and was covered by a semitransparent membrane. This report is the first to describe a case of thoracic EC in a goat whose sternum was not developed fully and was not connected to the ribs. It is also the first paper to describe three-dimensional images of this condition constructed from computed tomography scans.
我们通过x线摄影和计算机断层扫描诊断了一只2天大的雌性Toggenburg山羊胸廓异位(EC)。这只山羊出生时患有EC,胸骨缺陷和脐上腹壁,但没有坎特雷尔综合征的存在。尸检和组织病理学结果表明,受影响的孩子有心脏畸形,左心室增大。结果显示心脏(9 x 5 x 5 cm)位于胸腔外,并被半透明膜覆盖。本报告首次报道了山羊胸骨未发育完全且未与肋骨相连的胸椎EC病例。这也是第一篇描述通过计算机断层扫描构建的这种情况的三维图像的论文。
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引用次数: 1
Identification of multiple genetic loci in the mouse controlling immobility time in the tail suspension and forced swimming tests. 小鼠悬尾和强制游泳试验中控制不动时间的多个基因位点的鉴定。
Pub Date : 2015-05-01 DOI: 10.14943/JJVR.63.2.53
Ahmed F. Abou-Elnaga, Daisuke Torigoe, M. Fouda, R. Darwish, U. Abou-Ismail, M. Morimatsu, T. Agui
Depression is one of the most famous psychiatric disorders in humans in all over the countries and considered a complex neurobehavioral trait and difficult to identify causal genes. Tail suspension test (TST) and forced swimming test (FST) are widely used for assessing depression-like behavior and antidepressant activity in mice. A variety of antidepressant agents are known to reduce immobility time in both TST and FST. To identify genetic determinants of immobility duration in both tests, we analyzed 101 F2 mice from an intercross between C57BL/6 and DBA/2 strains. Quantitative trait locus (QTL) mapping using 106 microsatellite markers revealed three loci (two significant and one suggestive) and five suggestive loci controlling immobility time in the TST and FST, respectively. Results of QTL analysis suggest a broad description of the genetic architecture underlying depression, providing underpinnings for identifying novel molecular targets for antidepressants to clear the complex genetic mechanisms of depressive disorders.
抑郁症是世界上最著名的人类精神疾病之一,被认为是一种复杂的神经行为特征,难以确定病因基因。尾悬试验(TST)和强迫游泳试验(FST)被广泛用于评估小鼠抑郁样行为和抗抑郁活性。已知多种抗抑郁药物可减少TST和FST的静止时间。为了确定两种实验中固定时间的遗传决定因素,我们分析了101只来自C57BL/6和DBA/2菌株杂交的F2小鼠。利用106个微卫星标记进行定量性状位点(QTL)定位,分别发现3个位点(2个显著位点和1个提示位点)和5个提示位点控制静止时间。QTL分析的结果为抑郁症的遗传结构提供了广泛的描述,为确定抗抑郁药物的新分子靶点以清除抑郁症复杂的遗传机制提供了基础。
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引用次数: 2
Interaction between metabolic challenges and productivity in high yielding dairy cows. 高产奶牛代谢挑战与生产力的相互作用。
Pub Date : 2015-02-01 DOI: 10.14943/JJVR.63.SUPPL.S1
G. Opsomer
The onset of lactation in modern dairy cows is characterized by a negative energy balance, due to a drastic increase in energy requirements for milk yield and a simultaneous depression in dry matter intake around parturition. Prioritization of milk yield over maternal body functions is a universal biological strategy in all lactating mammals to buffer the newborn's nutrition from fluctuations in the dam's energetic status. Consequently, in case of an energy deficiency, the dam will mobilize fat and protein reserves in order to safeguard milk yield. During decades of one-sided selection for milk yield, man has exploited the cow's potential to prioritize mammary energy supply without an equivalent progress in dry matter intake capacity. Consequently, genetic selection for milk yield has widened the gap between energy expenditure and energy intake, and has increased the cow's inclination to respond to energy deficiencies in the transition period by aggressive body tissue breakdown. Chronically elevated concentrations of non-esterified fatty acids and ketone bodies have been demonstrated to affect multiple organ systems including the immune system, the reproductive axis and the liver and are, in contrast to absolute milk yield, closely and consistently related to the final incidence of reproductive disorders.
现代奶牛泌乳的开始表现为负能量平衡,这是由于产奶能量需求的急剧增加和分娩前后干物质摄入量的同时下降。产奶量优先于母体身体功能是所有哺乳期哺乳动物的普遍生物学策略,以缓冲新生儿的营养从大坝的能量状态波动。因此,在能量不足的情况下,大坝将动员脂肪和蛋白质储备,以保证产奶量。在几十年对产奶量的片面选择中,人类利用了奶牛的潜力,优先考虑乳腺能量供应,而没有在干物质摄入能力方面取得同等进展。因此,产奶量的遗传选择扩大了能量消耗和能量摄入之间的差距,并增加了奶牛在过渡时期通过剧烈的身体组织破坏来应对能量缺乏的倾向。非酯化脂肪酸和酮体浓度的长期升高已被证明会影响多个器官系统,包括免疫系统、生殖轴和肝脏,而且与绝对产奶量相反,它们与生殖疾病的最终发病率密切相关。
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引用次数: 16
Organ-specific changes in norepinephrine turnover against various stress conditions in thermoneutral mice. 热中性小鼠在各种应激条件下去甲肾上腺素转换的器官特异性变化。
Pub Date : 2014-08-01 DOI: 10.14943/JJVR.62.3.117
Y. Teramura, A. Terao, Y. Okada, Junichi Tomida, Y. Okamatsu-Ogura, K. Kimura
The effects of three stressors of different categories, namely cold exposure, immobilization, and lipopolysaccharide (LPS) treatment, on sympathetic nerve activity were examined by assessing its biochemical index norepinephrine (NE) turnover in peripheral organs of C57BL/6 mice. NE turnover was assessed by measuring the decrease in the organ NE concentration 3 h after inhibition of catecholamine biosynthesis with alpha-methyl-p-tyrosine. NE turnover in brown adipose tissue (BAT) in the room temperature (23 degrees C) control group was as high as that in the cold exposure (4 degrees C) group. Similarly, the mRNA level of the thermogenic marker uncoupling protein 1 (UCP1) in the room temperature control group was as high as that in the cold exposure group. As sympathetic stimulation upregulates the UCP1 mRNA level, we thought that sympathetic nerve tonus in BAT was already accelerated at room temperature. To exclude factors affecting basal sympathetic nerve activity, mice housed at thermoneutral temperature (30 degrees C) were used as controls for the subsequent experiments. In this condition, cold exposure accelerated NE turnover in the BAT, as well as heart and pancreas. The corticosterone level showed a higher trend in the cold exposure group in comparison to the control group. Immobilization accelerated NE turnover in the spleen, pancreas, and white adipose tissue and elevated the corticosterone level. LPS (3 mg/kg, i.p.) did not affect NE turnover in all peripheral organs but elevated the corticosterone level. In summary, the sympathetic nervous and adrenocortical responses to three stressors differed greatly. In particular, sympathetic responses showed clear organ-specific acceleration patterns. This important feature may improve our understanding of the multiplicity of biological responses.
通过测定C57BL/6小鼠外周器官去甲肾上腺素(NE)的生化指标,研究了冷暴露、固定化和脂多糖(LPS)处理3种不同类型应激源对交感神经活性的影响。通过测定α -甲基-对酪氨酸抑制儿茶酚胺生物合成3小时后器官NE浓度的下降来评估NE的周转率。室温(23℃)对照组棕色脂肪组织(BAT) NE周转率与冷暴露(4℃)组相同。同样,室温对照组产热标志解偶联蛋白1 (UCP1) mRNA表达水平与冷暴露组相同。由于交感刺激上调了UCP1 mRNA水平,我们认为室温下BAT的交感神经张力已经加速。为了排除影响基础交感神经活动的因素,将小鼠置于热中性温度(30℃)下作为后续实验的对照。在这种情况下,寒冷暴露加速了BAT以及心脏和胰腺的NE转换。与对照组相比,冷暴露组的皮质酮水平显示出更高的趋势。固定加速了脾脏、胰腺和白色脂肪组织的NE转换,并提高了皮质酮水平。LPS (3mg /kg, i.p.)不影响所有外周器官的NE转换,但升高皮质酮水平。综上所述,交感神经和肾上腺皮质对三种应激源的反应差异很大。特别是,交感神经反应显示出明显的器官特异性加速模式。这一重要特征可以提高我们对生物反应多样性的理解。
{"title":"Organ-specific changes in norepinephrine turnover against various stress conditions in thermoneutral mice.","authors":"Y. Teramura, A. Terao, Y. Okada, Junichi Tomida, Y. Okamatsu-Ogura, K. Kimura","doi":"10.14943/JJVR.62.3.117","DOIUrl":"https://doi.org/10.14943/JJVR.62.3.117","url":null,"abstract":"The effects of three stressors of different categories, namely cold exposure, immobilization, and lipopolysaccharide (LPS) treatment, on sympathetic nerve activity were examined by assessing its biochemical index norepinephrine (NE) turnover in peripheral organs of C57BL/6 mice. NE turnover was assessed by measuring the decrease in the organ NE concentration 3 h after inhibition of catecholamine biosynthesis with alpha-methyl-p-tyrosine. NE turnover in brown adipose tissue (BAT) in the room temperature (23 degrees C) control group was as high as that in the cold exposure (4 degrees C) group. Similarly, the mRNA level of the thermogenic marker uncoupling protein 1 (UCP1) in the room temperature control group was as high as that in the cold exposure group. As sympathetic stimulation upregulates the UCP1 mRNA level, we thought that sympathetic nerve tonus in BAT was already accelerated at room temperature. To exclude factors affecting basal sympathetic nerve activity, mice housed at thermoneutral temperature (30 degrees C) were used as controls for the subsequent experiments. In this condition, cold exposure accelerated NE turnover in the BAT, as well as heart and pancreas. The corticosterone level showed a higher trend in the cold exposure group in comparison to the control group. Immobilization accelerated NE turnover in the spleen, pancreas, and white adipose tissue and elevated the corticosterone level. LPS (3 mg/kg, i.p.) did not affect NE turnover in all peripheral organs but elevated the corticosterone level. In summary, the sympathetic nervous and adrenocortical responses to three stressors differed greatly. In particular, sympathetic responses showed clear organ-specific acceleration patterns. This important feature may improve our understanding of the multiplicity of biological responses.","PeriodicalId":344589,"journal":{"name":"The Japanese journal of veterinary research","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128092083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Plastic problem in Africa. 非洲的塑料问题。
Pub Date : 2013-02-01 DOI: 10.14943/JJVR.61.SUPPL.S1
N. Bashir
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引用次数: 43
Isolation of sporocyst broodsacs of the genus Leucochloridium (Leucochloridiidae: Trematoda) from the intermediate host, Succinea lauta, in Japan. 从日本琥珀属中间寄主中分离出囊孢囊的研究。
Pub Date : 2011-08-01 DOI: 10.14943/JJVR.59.2-3.101
Seitaro Yamada, S. Fukumoto
Green- or brown-striped trematode sporocyst broodsacs typical of Leucochloridium infecting the ocular tentacles of a land snail, Succinea lauta, were collected in Abashiri, Hokkaido in northern Japan (N43 degrees 59', E144 degrees 14') in June of 2000 and 2001. The metacercariae isolated from the sporocyst broodsac were morphologically identified as Leucochloridium spp. (Leucoclhoridiidae Poche). This report is the first to describe evidential specimens of the sporocyst broodsac of the genus Leucochloridium Carus, 1835, infecting the intermediate host in Japan, suggesting that Leucochloridium spp. completes their life cycle in Hokkaido, Japan.
2000年6月和2001年6月,在日本北部北海道Abashiri(北纬43度59′,东经144度14′)采集到一种典型的浅绿色或棕色条纹吸虫孢子囊,感染了陆地蜗牛lauta的眼触须。从孢子囊卵囊中分离得到的囊蚴经形态学鉴定为Leucochloridium spp. (Leucoclhoridiidae Poche)。本报告首次描述了1835年在日本感染中间宿主的Leucochloridium Carus属孢子囊卵囊的证据标本,表明Leucochloridium spj .在日本北海道完成了其生命周期。
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引用次数: 5
An H5N1 highly pathogenic avian influenza virus that invaded Japan through waterfowl migration. H5N1高致病性禽流感病毒通过水禽迁徙入侵日本。
Pub Date : 2011-08-01 DOI: 10.14943/JJVR.59.2-3.89
M. Kajihara, K. Matsuno, E. Simulundu, M. Muramatsu, O. Noyori, Rashid Manzoor, E. Nakayama, Manabu Igarashi, Daisuke Tomabechi, R. Yoshida, M. Okamatsu, Y. Sakoda, Kimihito Ito, H. Kida, A. Takada
In 2010, an H5N1 highly pathogenic avian influenza virus (HPAIV) was isolated from feces of apparently healthy ducks migrating southward in Hokkaido, the northernmost prefecture of Japan. The H5N1 HPAIVs were subsequently detected in domestic and wild birds at multiple sites corresponding to the flyway of the waterfowl having stopovers in the Japanese archipelago. The Hokkaido isolate was genetically nearly identical to H5N1 HPAIVs isolated from swans in the spring of 2009 and 2010 in Mongolia, but less pathogenic in experimentally infected ducks than the 2009 Mongolian isolate. These findings suggest that H5N1 HPAIVs with relatively mild pathogenicity might be selected and harbored in the waterfowl population during the 2009-2010 migration seasons. Our data provide "early warning" signals for preparedness against the unprecedented situation in which the waterfowl reservoirs serve as perpetual sources and disseminators of HPAIVs.
2010年,在日本最北部的北海道,从向南迁徙的表面健康的鸭子的粪便中分离出H5N1高致病性禽流感病毒(HPAIV)。随后在与在日本群岛停留的水禽的飞行路线相对应的多个地点在家禽和野鸟中发现了H5N1型hpai病毒。北海道分离株在遗传上与2009年和2010年春季在蒙古从天鹅中分离出的H5N1 hpaiv几乎相同,但在实验感染的鸭子中的致病性低于2009年蒙古分离株。这些结果表明,在2009-2010年迁徙季节,致病性相对较轻的H5N1型hpaiv可能在水禽种群中被选择和窝藏。我们的数据提供了“早期预警”信号,为防范水禽水库成为hpaiv永久来源和传播者的前所未有的情况做好准备。
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引用次数: 28
Inactivation of SARS coronavirus by means of povidone-iodine, physical conditions, and chemical reagents. 聚维酮碘、物理条件和化学试剂灭活SARS冠状病毒。
Pub Date : 2004-11-01 DOI: 10.14943/JJVR.52.3.105
H. Kariwa, N. Fujii, I. Takashima
The efficacy of several povidone-iodine (PVP-I) products, a number of other chemical agents, and various physical conditions were evaluated for their ability to inactivate the severe acute respiratory syndrome coronavirus (SARS-CoV). Treatment of SARS-CoV with PVP-I products for 2 min reduced the virus infectivity from 1.17 x 10(6) TCID50/ml to below the detectable level. The efficacy of 70% ethanol was equivalent to that of PVP-I products. Fixation of SARS-CoV-infected Vero E6 cells with a fixative including formalin, glutaraldehyde, methanol, and acetone for 5 min or longer eliminated all infectivity. Heating the virus at 56 degrees C for 5 min dramatically reduced the infectivity of the virus from 2.6 x 10(7) to 40 TCID50/ml, whereas heating the virus for 60 min or longer eliminated all infectivity. Irradiation with ultraviolet light at 134 microW/cm2 for 15 min reduced the infectivity from 3.8 x 10(7) to 180 TCID50/ml; however, prolonged irradiation (60 min) failed to eliminate the remaining virus, leaving 18.8 TCID50/ml. We believe that these findings will be useful for the implementation of infection control measures against SARS, and for the establishment of effective guidelines for the prevention of SARS outbreaks.
对几种聚维酮-碘(PVP-I)产品、一些其他化学制剂和各种物理条件对严重急性呼吸综合征冠状病毒(SARS-CoV)灭活的能力进行了评估。用PVP-I产品治疗SARS-CoV 2 min后,病毒传染性从1.17 × 10(6) TCID50/ml降至可检测水平以下。70%乙醇的效果与PVP-I产品相当。用含福尔马林、戊二醛、甲醇和丙酮的固定剂固定sars - cov感染的Vero E6细胞5分钟或更长时间可消除所有传染性。在56℃下加热5分钟可显著降低病毒的传染性,从2.6 × 10(7)降至40 TCID50/ml,而加热60分钟或更长时间可消除所有传染性。134 μ m /cm2紫外光照射15 min,传染性由3.8 × 10(7)降至180 TCID50/ml;然而,长时间照射(60 min)未能消除剩余的病毒,留下18.8 TCID50/ml。我们相信这些研究结果将有助推行感染控制措施,以及制定有效的预防SARS爆发的指引。
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引用次数: 68
期刊
The Japanese journal of veterinary research
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