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1329篇 您的检索式:作者名="Guillermo"
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1A review of Helicobacter pylori diagnosis, treatment, and methods to detect eradication显示文摘Helicobacter pylori(H. pylori) affects nearly half of the world's population and, thus, is one of the most frequent and persistent bacterial infections worldwide. H. pylori is associated with peptic ulcer disease, gastric ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Various diagnostic methods exist to detect infection, and the choice of one method or another depends on several factors, such as accessibility, advantages and disadvantages of each method, cost, and the age of patients. Once H. pylori infection is diagnosed, the clinician decides whether treatment is necessity, according to the patient's clinical condition. Typically, eradication of H. pylori is recommended for treatment and prevention of the infection. Cure rates with the standard triple therapy are acceptable, and effective quadruple therapies, sequential therapies, and concomitant therapies have been introduced as key alternatives to treat H. pylori infection. In this work, we review the main diagnostic methods used to identify H. pylori infection and to confirm eradication of infection. In addition, key factors related to treatment are reviewed.Elvira Garza-González Guillermo Ignacio Perez-Perez Héctor Jesús Maldonado-Garza Francisco Javier Bosques-Padilla 2014World Journal of Gastroenterology2014,20,6:17
2Hemoconcentration is a poor predictor of severity in acute pancreatitis显示文摘AIM: To determine whether the hematocrit (Hct) at admission or at 24 h after admission was associated with severe acute pancreatitis (AP), organ failure (OF), and pancreatic necrosis.METHODS: A total of 336 consecutive patients with a first AP episode were studied. Etiology, Hct values at admission and at 24 h, development of severe AP according to Atlanta's criteria, pancreatic necrosis, OF and mortality were recorded. Hemoconcentration was defined as Hct level >44% for males and >40% for females. The t-test and χ2 test were used to assess the association of hemoconcentration to the severity, necrosis and OF.Diagnostic accuracy was also determined.RESULTS: Biliary disease was the most frequent etiology(n = 148). Mean Hct levels at admission were 41±6%for females and 46±7% for males (P<0.01). Seventyeight (23%) patients had severe AP, and OF developed in 45 (13%) patients. According to contrast-enhanced computed tomography scan, 36% (54/150) patients showed pancreatic necrosis. Hct levels were elevated in58% (55/96) and 61% (33/54) patients with interstitial and necrotizing pancreatitis, respectively. Neither Hct levels at admission nor hemoconcentration at 24 h were associated with the severity, necrosis or OF. Sensitivity,specificity and positive predictive values for both determinations were very low; and negative predictive values were between 61% and 86%, being the highest value for OF.CONCLUSION: Hct is not a useful marker to predict a worse outcome in acute pancreatitis. In spite of the high negative predictive value of hemoconcentration, the prognosis gain is limited due to an already high incidence of mild disease.José M.Remes-Troche Andrés Duarte-Rojo Gustavo Morales Guillermo Robles-Díaz 2005World Journal of Gastroenterology2005,11,44:16
3The wonders of BMP9:From mesenchymal stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism to regenerative medicine显示文摘Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological roles.These roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ systems.Disruptions of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP proteins.Although it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs.The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of BMP9.Furthermore,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism.This review aims to summarize our current understanding of BMP9 across biology and the body.Sami Mostafa Mikhail Pakvasa Elam Coalson Allen Zhu Alex Alverdy Hector Castillo Jiaming Fan Alex Li Yixiao Feng Di Wu Elliott Bishop Scott Du Mia Spezia Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Sherwin S·Ho Aravind Athiviraham Michael J·Lee Jennifer Moriatis Wolf Guillermo A·Ameer Hue H·Luu Rex C·Haydon Jason Strelzow Kelly Hynes Tong-Chuan He Russell R·Reid 2019Genes & Diseases2019,6,3:15
4Neural EGF-like protein 1(NELL-1):Signaling crosstalk in mesenchymal stem cells and applications in regenerative medicine显示文摘Bone tissue regeneration holds the potential to solve both osteoporosis and large skeletal defects,two problems associated with significant morbidity.The differentiation of mesenchymal stem cells into the osteogenic lineage requires a specific microenvironment and certain osteogenic growth factors.Neural EGF Like-Like molecule 1(NELL-1)is a secreted glycoprotein that has proven,both in vitro and in vivo,to be a potent osteo-inductive factor.Furthermore,it has been shown to repress adipogenic differentiation and inflammation.NELL-1 can work synergistically with other osteogenic factors such as Bone Morphogenic Protein(BMP)2 and9,and has shown promise for use in tissue engineering and as a systemically administered drug for the treatment of osteoporosis.Here we provide a comprehensive up-to-date review on the molecular signaling cascade of NELL-1 in mesenchymal stem cells and potential applications in bone regenerative engineering.Mikhail Pakvasa Alex Alverdy Sami Mostafa Eric Wang Lucy Fu Alexander Li Leonardo Oliveira Aravind Athiviraham Michael J.Lee Jennifer Moriatis Wolf Tong-Chuan He Guillermo A.Ameer Russell R.Reid 2017Genes & Diseases2017,4,3:13
5Ulcerative colitis in smokers,non-smokers and ex-smokers显示文摘Smoking is a major environmental factor that interferes in the establishment and clinical course of ulcerative colitis (UC). Firstly, the risk of smoking status impact in the development of UC is reviewed, showing that current smoking has a protective association with UC. Similarly, being a former smoker is associated with an increased risk of UC. The concept that smoking could have a role in determining the inflammatory bowel disease phenotype is also discussed. Gender may also be considered, as current smoking delays disease onset in men but not in women. No clear conclusions can be driven from the studies trying to clarify whether childhood passive smoking or prenatal smoke exposure have an influence on the development of UC, mainly due to methodology flaws. The influence of smoking on disease course is the second aspect analysed. Some studies show a disease course more benign in smokers that in non-smokers, with lower hospitalizations rates, less flare-ups, lower use of oral steroids and even less risk of proximal extension. This is not verified by some other studies. Similarly, the rate of colectomy does not seem to be determined by the smoking status of the patient. The third issue reviewed is the use of nicotine as a therapeutic agent. The place of nicotine in the treatment of UC is unclear, although it could be useful in selected cases, particularly in recent ex-smokers with moderate but refractory attacks of UC. Finally, the effect of smoking cessation in UC patients is summarised. Given that smoking represents a major worldwide cause of death, for inpatients with UC the risks of smoking far outweigh any possible benefit. Thus, physicians should advise, encourage and assist UC patients who smoke to quit.Guillermo Bastida Belén Beltrán 2011World Journal of Gastroenterology2011,17,22:13
63-D bioprinting technologies in tissue engineering and regenerative medicine:Current and future trends显示文摘Advances in three-dimensional(3D)printing have increased feasibility towards the synthesis of living tissues.Known as 3D bioprinting,this technology involves the precise layering of cells,biologic scaffolds,and growth factors with the goal of creating bioidentical tissue for a variety of uses.Early successes have demonstrated distinct advantages over conventional tissue engineering strategies.Not surprisingly,there are current challenges to address before 3D bioprinting becomes clinically relevant.Here we provide an overview of 3D bioprinting technology and discuss key advances,clinical applications,and current limitations.While 3D bioprinting is a relatively novel tissue engineering strategy,it holds great potential to play a key role in personalized medicine.Elliot S.Bishop Sami Mostafa Mikhail Pakvasa Hue H.Luu Michael J.Lee Jennifer Moriatis Wolf Guillermo A.Ameer Tong-Chuan He Russell R.Reid 2017Genes & Diseases2017,4,4:10
7The Genome of Cucurbita argyrosperma (Silver- Seed Gourd) Reveals Faster Rates of Protein- Coding Gene and Long Noncoding RNA Turnover and Neofunctionalization within Cucurbita显示文摘Whole-genome duplications are an important source of evolutionary novelties that change the mode and tempo at which genetic elements evolve within a genome. The Cucurbita genus experienced a wholegenome duplication around 30 million years ago, although the evolutionary dynamics of the coding and noncoding genes in this genus have not yet been scrutinized. Here, we analyzed the genomes of four Cucurbita species, in eluding a newly assembled genome of Cucurbita argyrosperma, and compared the gene con tents of these species with those of five other members of the Cucurbitaceae family to assess the evolutionary dynamics of protein-coding and long intergenic noncoding RNA (lincRNA) genes after the genome duplication. We report that Cucurbita genomes have a higher protein-coding gene birth-death rate compared with the genomes of the other members of the Cucurbitaceae family. C. argyrosperma gene families associated with pollination and transmembrane transport had significantly faster evolutionary rates. lincRNA families showed high levels of gene turnover throughout the phylogeny, and 67.7% of the lincRNA families in Cucurbita showed evidence of birth from the neofunctionalization of previously existing protein-coding genes. Collectively, our results suggest that the whole-genome duplication in Cucurbita resulted in faster rates of gene family evolution through the neofunctionalization of duplicated genes.Josue Barrera-Red on do Enrique Ibarra-Laclette Alejandra Vazquez-Lobo Yocelyn T. Gutierrez-Guerrero Guillermo Sanchez de la Vega Daniel Pinero Salvador Montes-Hernandez Rafael Lira-Saade Luis E. Eguiarte 2019Molecular Plant2019,12,4:9
8Taking advantage of the potential of mesenchymal stromal cells in liver regeneration:Cells and extracellular vesicles as therapeutic strategies显示文摘Cell-based therapies for acute and chronic liver diseases are under continuous progress. Mesenchymal stem/stromal cells(MSCs) are multipotent cells able to migrate selectively to damaged tissue and contribute to its healing and regeneration. The MSC pro-regenerative effect occurs due to their immunomodulatory capacity and their ability to produce factors that promote cell protection and survival. Likewise,it has been observed that part of their paracrine effect is mediated by MSC-derived extracellular vesicles(EVs). EVs contain proteins,lipids and nucleic acids(DNA,m RNA,mi RNA,lnc RNA) from the cell of origin,allowing for intercellular communication. Recently,different studies have demonstrated that MSC-derived EVs could reproduce,at least in part,the biological effects obtained by MSCbased therapies. Moreover,due to EVs' stability for long periods of time and easy isolation methods they have become a therapeutic option to MSCs treatments. This review summarizes the latest results achieved in clinical trials using MSCs as cell therapy for liver regeneration,the role of EVs in liver physiopathology and the potential of MSC-derived EVs as intercellular mediators and therapeutic tools in liver diseases.Esteban Juan Fiore Luciana María Domínguez Juan Bayo Mariana Gabriela García Guillermo Daniel Mazzolini 2018World Journal of Gastroenterology2018,24,23:9
9Aquaporins:Their role in cholestatic liver disease显示文摘This review focuses on current knowledge on hepato-cyte aquaporins(AQPs)and their significance in bile formation and cholestasis.Canalicular bile secretion results from a combined interaction of several solute transporters and AQP water channels that facilitate water flow in response to the osmotic gradients created. During choleresis,hepatocytes rapidly increase their canalicular membrane water permeability by modulating the abundance of AQP8.The question was raised as to whether the opposite process,i.e.a decreased canalicular AQP8 expression would contribute to the development of cholestasis.Studies in several experimental models of cholestasis,such as extrahepatic obstructive cholestasis,estrogen-induced cholestasis, and sepsis-induced cholestasis demonstrated that the protein expression of hepatocyte AQP8 was impaired. In addition,biophysical studies in canalicular plasma membranes revealed decreased water permeability associated with AQP8 protein downregulation.The combined alteration in hepatocyte solute transporters and AQP8 would hamper the efficient coupling of osmotic gradients and canalicular water flow.Thus cholestasis may result from a mutual occurrence of impaired solute transport and decreased water permeability.Guillermo L Lehmann Maria C Larocca Leandro R Soria Raúl A Marinelli 2008World Journal of Gastroenterology2008,14,46:8
10产前保健有效预防孕产妇死亡和严重疾病的证据概述显示文摘Guillermo Carroli Cleonr Rooney Jose Villar 2005生殖与避孕2005,25,4:7
11PRSS1 and SPINK1 mutations in idiopathic chronic and recurrent acute pancreatitis显示文摘AIM: To identify gene mutations in PRSS1 and SPINK1 in individuals with early onset idiopathic chronic or recurrent acute pancreatitis.METHODS: The cationic trypsinogen gene(PRSS1; exons 2 and 3) and the serine protease inhibitor Kazal 1 gene(SPINK1; exon 3) were selectively amplified and sequenced from blood samples of 19 patients admitted to the Pancreas Clinic at our institution with chronic pancreatitis and/or idiopathic recurrent acute pancreatitis that were diagnosed or with onset before age 35. Fifty healthy volunteers served as controls. Whole blood samples were collected and gene specific sequences were amplified by polymerase chain reaction(PCR). All PCR products were subsequently sequenced in order to identify the presence of any mutations.RESULTS: Nineteen patients with pancreatitis(14 males; median age 24 years, range 15-48 years) were included in this study, of which five showed the presence of gene mutations. Direct sequencing results indicated the presence of two previously unidentified mutations in exon 2 of PRSS1(V39E and N42S) in two patients with recurrent acute pancreatitis. Two cases had the N34 S SPINK1 mutation. Analysis of the relatives of one patient homozygous for this mutation showed that five of the six family members carried the N34 S SPINK1 mutation. Of these members, three were healthy heterozygous carriers and two were homozygotes(one sibling had diabetes, the other was healthy). Another patient was heterozygous for a novel SPINK1 mutation located on exon 3(V46D). All members from this patient's family had normal genotypes, indicating that it was a de novo mutation. No mutations in either gene were present in the control subjects. CONCLUSION: Two novel PRSS1 mutations and one novel SPINK1 mutation were identified in Mexican patients with early onset idiopathic recurrent acute pancreatitis.Mario Pelaez-Luna Guillermo Robles-Diaz Samuel Canizales-Quinteros Maria T Tusié-Luna 2014World Journal of Gastroenterology2014,20,33:7
12Use of high-resolution X-ray computed tomography and 3D image analysis to quantify mineral dissemination and pore space in oxide copper ore particles显示文摘Mineral dissemination and pore space distribution in ore particles are important features that influence heap leaching performance. To quantify the mineral dissemination and pore space distribution of an ore particle, a cylindrical copper oxide ore sample(Φ4.6 mm × 5.6 mm) was scanned using high-resolution X-ray computed tomography(HRXCT), a nondestructive imaging technology, at a spatial resolution of 4.85 μm. Combined with three-dimensional(3D) image analysis techniques, the main mineral phases and pore space were segmented and the volume fraction of each phase was calculated. In addition, the mass fraction of each mineral phase was estimated and the result was validated with that obtained using traditional techniques. Furthermore, the pore phase features, including the pore size distribution, pore surface area, pore fractal dimension, pore centerline, and the pore connectivity, were investigated quantitatively. The pore space analysis results indicate that the pore size distribution closely fits a log-normal distribution and that the pore space morphology is complicated, with a large surface area and low connectivity. This study demonstrates that the combination of HRXCT and 3D image analysis is an effective tool for acquiring 3D mineralogical and pore structural data.Bao-hua Yang Ai-xiang Wu Guillermo A.Narsilio Xiu-xiu Miao Shu-yue Wu 2017International Journal of Minerals,Metallurgy and Materials2017,24,9:7
13让肾脏健康人人可享,处处可及——从预防到诊治显示文摘Around 850 million people currently are affected by different types of kidney disorders.Up to 1 in 10 adults worldwide has chronic kidney disease(CKD),which is invariably irreversible and mostly progressive.The global burden of CKD is increasing,and CKD is projected to become the fifth most common cause of years of life lost globally by 2040.If CKD remains uncontrolled and if the affected person survives the ravages of cardiovascular and other complications of the disease,CKD progresses to endstage kidney disease,where life cannot be sustained without dialysis therapy or kidney transplantation.Hence,CKD is a major cause of catastrophic health expenditure.Philip Kam Tao Guillermo Garcia Garcia Siu Fai Lui Sharon Andreoli Winston Wing Shing Fung Anne Hradsky Latha Kumaraswami Vassilios Liakopoulos Ziyoda Rakhimova Gamal Saadi Luisa Strani Ifeoma Ulasi Kamyar Kalantar Zadeh 2020肾脏病与透析肾移植杂志2020,29,1:6
14K-ras^G12V transformation leads to mitochondrial dysfunction and a metabolic switch from oxidative phosphorylation to glycolysis显示文摘增加的氧气的 glycolysis 和氧化应力是癌症房间新陈代谢的重要特征,但是内在的生物化学、分子的机制留下逃犯。用四圜素可诱导的模型,我们显示出 K 地岬 G12V 原因 mitochondrial 机能障碍,导致反应的氧的减少的呼吸,提高的 glycolysis,和增加的产生种类。K 地岬蛋白质与线粒体被联系,并且导致呼吸的链建筑群的快速的抑制 -- 我和在由影响 cyclosporin 敏感的渗透的 mitochondrial transmembrane 潜力的减少转移毛孔。而且, K 地岬 在 vitro 的 G12V 表示提高转变房间的能力允许新陈代谢的改编到高 glycolytic 新陈代谢在 vivo 形成肿瘤。我们的学习建议 mitochondrial 机能障碍的那正式就职是由 K 地岬 G12V 在癌症房间引起新陈代谢的变化和 ROS 应力,并且支持肿瘤开发。Yumin Hu Weiqin Lu Gang Chen Peng Wang Zhao Chen Yan Zhou Marcia Ogasawara Dunyaporn Trachootham Li Feng Helene Pelicano Paul J Chiao Michael J Keating Guillermo Garcia-Manero Peng Huang 2012Cell Research2012,22,2:6
15Differences in standing balance between patients with diplegic and hemiplegic cerebral palsy显示文摘Maintaining standing postural balance is important for walking and handling abilities in patients with cerebral palsy.This study included 23 patients with cerebral palsy(seven with spastic diplegia and16 with spastic hemiplegia),aged from 7 to 16 years of age.Standing posture balance measurements were performed using an AMTI model OR6-7 force platform with the eyes open and closed.Patients with diplegic cerebral palsy exhibited greater center of pressure displacement areas with the eyes open and greater center of pressure sway in the medial-lateral direction with the eyes open and closed compared with hemiplegic patients.Thus,diplegic patients exhibited weaker postural balance control ability and less standing stability compared with hemiplegic cerebral palsy patients.Valeska Gatica Rojas Guillermo Méndez Rebolledo Eduardo Guzman Muoz Natalia Ibarra Cortés Caterine Berrios Gaete Carlos Manterola Delgado 2013Neural Regeneration Research2013,8,26:6
16不同土地利用/覆被情景下生态系统减轻水库泥沙淤积的服务能力与经济价值模拟显示文摘以ArcGIS9.2为平台,构建了生态系统减轻水库泥沙淤积服务物质量和价值量评估模型。整合2000年的相关数据将此模型应用于二滩水库,并模拟了10种不同土地利用/覆被情景下集水区生态系统该项服务的能力和在水库使用年限内服务总价值的响应。结果表明:2000年,二滩水库集水区土壤保持量12.1亿.ta-1,高值区分布于雅砻江干流和支流水网附近。泥沙输移比在河道附近和水库周边较高。水库周边是最为主要的保沙区。水库使用年限内,集水区对于减轻二滩水库泥沙淤积服务总价值27.53亿元。集水区内不同结构类型的土地利用/覆被情景对保沙能力所产生的影响各异,模拟保沙量符合林地>草地>裸地>农田规律,农田保沙能力最弱,是二滩水库最为主要的产沙源。吴楠 高吉喜 苏德毕力格 罗遵兰 Driss Ennaanay Guillermo F.Mendoza 李岱青 田美荣 2009生态学报2009,29,11:6
17Accounting for intermediates: Production sharing and trade in value added显示文摘Robert C. Johnson Guillermo Noguera 2011Journal of International Economics2011,,2:6
18Stem cell therapy for chronic skin wounds in the era of personalized medicine:From bench to bedside显示文摘With the significant financial burden of chronic cutaneous wounds on the healthcare system,not to the personal burden mention on those individuals afflicted,it has become increasingly essential to improve our clinical treatments.This requires the translation of the most recent benchtop approaches to clinical wound repair as our current treatment modalities have proven insufficient.The most promising potential treatment options rely on stem cellbased therapies.Stem cell proliferation and signaling play crucial roles in every phase of the wound healing process and chronic wounds are often associated with impaired stem cell function.Clinical approaches involving stem cells could thus be utilized in some cases to improve a body’s inhibited healing capacity.We aim to present the laboratory research behind the mechanisms and effects of this technology as well as current clinical trials which showcase their therapeutic potential.Given the current problems and complications presented by chronic wounds,we hope to show that developing the clinical applications of stem cell therapies is the rational next step in improving wound care.Elam Coalson Elliot Bishop Wei Liu Yixiao Feng Mia Spezia Bo Liu Yi Shen Di Wu Scott Du Alexander J.Li Zhenyu Ye Ling Zhao Daigui Cao Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Rex C.Haydon Lewis Shi Aravind Athiviraham Michael J.Lee Jennifer Moriatis Wolf Guillermo A.Ameer Tong-Chuan He Russell R.Reid 2019Genes & Diseases2019,6,4:6
19Hyperphosphatemia after sodium phosphate laxatives in low risk patients:Prospective study显示文摘AIM:To establish the frequency of hyperphosphate-mia following the administration of sodium phosphate laxatives in low-risk patients. METHODS:One hundred consecutive ASAⅠ-Ⅱindividuals aged 35-74 years,who were undergoing colonic cleansing with oral sodium phosphate(OSP) before colonoscopy were recruited for this prospective study.Exclusion criteria:congestive heart failure, chronic kidney disease,diabetes,liver cirrhosis,intestinal obstruction,decreased bowel motility,increased bowel permeability,and hyperparathyroidism.The day before colonoscopy,all the participants entered a 24-h period of diet that consisted of 4 L of clear fluids with sugar or honey and 90 mL(60 g)of OSP in two 45-mL doses,5 h apart.Serum phosphate was measured before and after the administration of the laxative. RESULTS:The main demographic data(mean±SD) were:age,58.9±8.4 years;height,163.8±8.6 cm; weight,71±13 kg;body mass index,26±4;women, 66%.Serum phosphate increased from 3.74±0.56 to 5.58±1.1 mg/dL,which surpassed the normal value (2.5-4.5 mg/dL)in 87%of the patients.The highest serum phosphate was 9.6 mg/dL.Urea and creatinine remained within normal limits.Post-treatment OSP se-rum phosphate concentration correlated inversely with glomerular filtration rate(P<0.007,R 2=0.0755),total body water(P<0.001,R 2=0.156)and weight(P< 0.013,R 2=0.0635). CONCLUSION:In low-risk,well-hydrated patients, the standard dose of OSP-laxative-induced hyperphos-phatemia is related to body weight.Marcela Noemi Casais Guillermo Rosa-Diez Susana Pérez Elina Noemi Mansilla Susana Bravo Francisco Carlos Bonofiglio 2009World Journal of Gastroenterology2009,15,47:5
20家禽病毒性呼吸系统疾病的挑战及对策显示文摘在家禽业中需要重点防控的病毒性呼吸系统疾病有新城疫、传染性支气管炎、传染性喉气管炎、禽偏肺病毒病、禽流感。这类呼吸系统疾病的防控策略由于受到很多因素的影响,效果不一。结合生物安全、有效免疫、快速准确的诊断以及全面的现代管理技术综合性措施的实施可以获得较好防控效果。并且,了解家禽遗传因素、营养、管理和传染性疾病之间的互作有助于更好地防控家禽病毒性呼吸系统疾病。Guillermo Zavala 吕玲(译) 2012中国家禽2012,34,3:5
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