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银翘散治疗急性病毒性咽炎的临床和基础研究
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摘要
目的:
     1.利用病毒分离培养及荧光定量PCR方法检测分析急性咽炎患者不同呼吸道标本(鼻拭子、咽拭子及鼻灌洗)的病毒病原体,初步揭示急性咽炎的病毒感染谱;同时也比较不同呼吸道采样方法在成人急性咽炎病毒检测中的敏感性及检出效果,为临床有效的开展采样提供重要而实用的参考。
     2.观察中药经典方银翘散治疗急性病毒性咽炎的临床疗效,进一步以甲型流感病毒鼠小鼠模型评价其对流感病毒的体内抑制作用,从临床和动物实验两方面共同评价银翘散治疗急性咽炎致病原—流感病毒的疗效。
     方法:
     1.急性咽炎患者的呼吸道病毒病原体检测:入组标准:符合急性咽炎诊断标准及中医急喉痹诊断标准者;年龄在18-65岁之间,性别不限;急性起病,病程在3天内。入组的急性咽炎患者顺次采集咽拭子、鼻咽拭子及鼻灌洗标本,分别应用病毒分离培养(7种)及荧光定量PCR(15种)检测多种呼吸道病毒。其中,分离培养检测病原种类包括甲型流感(Flu A)、乙型流感(Flu B).副流感1-3型(PIV1~PIV3)、呼吸道合胞病毒(RSV)、腺病毒(ADV);荧光定量PCR检测病原种类包括Flu A、FluB、PIV1、PIV2、PIV3、PIV4、RSV、ADV.鼻病毒(RHV)、肠道病毒(EV)、人冠状病毒(HCoV-229E、OC43、NL63、HKUl).偏肺病毒(HMPV)。
     2.银翘散治疗急性病毒性咽炎的临床疗效观察:入组标准同上,另外必须为符合病毒学检测确诊的急性病毒性咽炎患者。入组患者按意愿分为银翘散治疗组及对照组,利用自拟症状量表作疗效观察。
     3.银翘散体内抗甲型流感药效:以甲型流感病毒FM1鼠肺适应株滴鼻感染NIH小鼠,制作病毒性肺炎模型,观察银翘散提取物治疗组和对照组的生存状态及检测肺指数,以苏木素-伊红染色(HE染色)法观察病理改变。
     结果:
     1.在检测的115个患者的345份样本中,病毒培养法检测的阳性标本合计22份,总病毒分离阳性率为6.38%;各种病毒的分离检出数从高至低依次为:甲型流感病毒>乙型流感病毒>呼吸道合胞病毒>腺病毒和副流感病毒;阳性标本中的病毒原体比例,流感病毒检出率最高,其他呼吸道病毒依次为:PIV、ADV、RSV。荧光定量PCR法检测的阳性标本数合计97份,总阳性率为28.12%。
     2.检出的病毒种类,以较为敏感的分子检测方法计,按检出率高低分别为普通冠状病毒>流感病毒>鼻病毒>腺病毒>副流感病毒>肠道病毒>呼吸道合胞病毒>偏肺病毒。
     3.两种病毒检测方法都显示,不同呼吸道标本类型的检出数从高至低依次为,鼻咽拭子>咽拭子>鼻灌洗液。
     4.共纳入115例急性咽炎患者,采样的平均时间点为发病后2.5±1.0天。共有80例患者(70%,80/115)经病毒检测证实至少有一种病毒感染。样本任意病毒检出率方面鼻咽拭子为81.25%(65/80、咽拭子为60%(48/80)、鼻灌洗为47.5%(38/80)。鼻咽拭子任意病毒检出率明显高于咽拭子(P<0.01)及鼻灌洗(P<0.01)。在所有的病毒检测中,鼻咽拭子的敏感性分别高于鼻灌洗(74%[95%CI=66-83] vs.45%[95%CI=35-55], P<0.01)与咽拭子(74%[95%CI=66-83] vs.48%[95%CI=39-59], P<0.01)。
     5.银翘散疗效观察临床研究共纳入病例80例,其中银翘散组60例,对照组20例,银翘散组比对照组在症状改善方面作用更加显著。治疗3天后银翘散组在咽痛、咽异物感、咽粘膜及悬雍垂红肿、咽侧索红肿症状体征改善方面明显优于对照组(P<0.05)。治疗6天后银翘散组与对照组相比,对咽痛、咽粘膜及悬雍垂红肿、咽后壁淋巴滤泡症状有明显的改善(P<0.05)。
     6.银翘散体内抗流感病毒实验结果显示,银翘散总提物(300mg/kg/d)可以一定程度减轻小鼠感染流感病毒引起的体重减轻等全身症状,降低因发生病毒性肺炎升高的肺指数,改善鼠肺间质性肺炎的病变,差异具有统计学意义(P<0.05)。结论:
     在成人急性咽炎患者中,多种呼吸道病毒都是重要的致病原,其中冠状病毒、鼻病毒和流感病毒是主要病原体,临床诊疗时应予更多的重视。对于这类患者选择合适的采样方法是提高检出率的关键,应首选性价比高的鼻咽拭子进行病毒检测。
     银翘散对急性病毒性咽炎的临床疗效显著,对可引起急性病毒性咽炎重要病原体之一的流感病毒是一种有效的治疗药物。综合临床床和基础研究的结果,银翘散对于急性病毒性咽炎(尤其是流感病毒引起)的临床治疗具有很大应用潜力和可行性。
Objective
     1.This study aimed to compare the sensitivities and rates of viral detection among oropharyngeal swab (OPS), nasopharyngeal swab (NPS) and NW in adults with acute pharyngitis by using Taqman real-time polymerase chain reaction (PCR) and virus culture, and to analyze the viral distribution of acute pharyngitis.
     2.To observed the clinical curative effect of acute pharyngi(?)s treated by Yinqiao Powder. And to inspect the antiviral effect of Yinqiao Powder in vivo.
     Methods
     1. the detection of respiratory viruses of acute pharyngitis:the inclusion were that accorded with the diagnosis criteria of acute pharyngitis and acute pharyngeal tumefaction,18years≤Age<60years, history of acute pharyngitis≤3days. Three consecutive samples were collected from each patient with acute pharyngitis by experienced physicians, in the following order oropharyngeal swab (OPS), nasopharyngeal swab (NPS) and nasal wash (NW). The specimens were tested for15respiratory viruses by PCR including influenza virus (A, B), parainfluenza virus (PIV1,2,3,4), rhinovirus, respiratory syncytial virus (RSV), adenovirus, enterovirus (EV), human coronavirus (HCoV-229E,OC43, NL63and HKU1), human metapneumovirus (HMPV). Also the specimens were tested for7respiratory viruses by virus culture, including Flu A, Flu B, PIV1, PIV2, PIV3, RSV, ADV.
     2. The clinical curative effect of acute pharyngitis treated by Yinqiao Powder:the inclusion were the same as above, in addition the patients should be viral laboratory-confirmed diagnosed. The patients were divided into two groups, Yinqiao Powder group or control group, suiting themselves. The clinical curative effect was observed with self-refit symptom scale.
     3. We use NIH mice which were intranasal inoculated with H1N1strain of influenza A virus, to observe the living conditions, determinate lung index, to observed pathological changes by hematoxylin-eosin staining (HE staining). Results
     1. During the study period,115patients of acute pharyngitis were enrolled,345specimens were collected. There were23positive specimens tested by virus culture, the positive detection rate was3.67%. The sequence of viruses amount displayed from the highest to the lowest, which was human coronavirus, influenza virus, rhinovirus, adenovirus, parainfluenza virus, enterovirus, respiratory syncytial virus and human metapneumovirus.
     2. PCR and virus culture detection showed that the detection rate of different specimens displayed from highest, to lowest, which was NPS, OPS and NW.
     3.115patients of acute pharyngitis were enrolled. The mean days from onset of illness to samples collection were2.5days (SD,1.0). A total of80patients (70%,80/115) were detected at least one type of virus. NPS samples identified81.25%(65/80) the infected patients, which was the highest detection rate. NW samples detected47.5%(38/80) of the infected patients and OPS samples60%(48/80). The detection rate of any virus in NPS was significant higher than that in NW (P<0.01) and OPS (P<0.01) respectively. In detection of all viruses, the sensitivity of NPS was significantly higher than NW (74%[95%CI=66-83] vs.45%[95%CI=35-55], P<0.01) and OPS (74%[95%CI=66-83] vs.48%[95%CI=39-59], P<0.01) respectively.
     4. The clinical research of clinical curative effect of Yinqiao Powder included80patients (60patients of Yinqiao Powder group,20patients of control group). For symptom improvement, the Yinqiao Powder group was better than control group. After3days of treatment, for the symptom and sign improvement of sore throat, throat sensation, redness and swollen of uvula and pharyngeal mucosa, redness and swollen of lateral pharyngeal bands, the Yinqiao Powder was significant better than control group (P<0.05). After6days of treatment, for the symptom and sign improvement of sore throat, redness and swollen of uvula and pharyngeal mucosa, the Yinqiao Powder was significant better than control group (P<0.05)
     5. The antiviral effect of Yinqiao Powder in vivo showed total Yinqiao Powder extract (300mg/kg/d) could reduced the the systemic symptoms, lung index, the scope of the rat lung lesions (P<0.05).
     Conclusion
     In adults, acute pharyngitis were caused by many kinds of respiratory viruses, and the major pathogen were human coronavirus, influenza virus and rhinovirus. The choice of specimen would markedly affect the detection rate of respiratory viruses. In this study we concluded the NPS collection was the best cost-utility sampling method in patients with acute pharyngitis.
     Yinqiao Powder made the significant symptom and sign improvement of acute viral pharyngitis. And Yinqiao Powder also was effective to influenza in vivo. Therefore Yinqiao Powder was powered to the treatment of acute viral pharyngitis, especially for the influenza infection.
引文
[I]Melio FR, Holmes DK. Upper respiratory tract infections. In:Rosen P Barkin RM, eds. Emergency Medicine. Concepts and Clinical Practice[J].1998,4th ed. St. Louis: Mosby:1529-1553.
    [2]Cooper RJ, Hoffman JR, Bartlett JG, et al. Principles of appropriate antibiotic use for acute pharyngitis in adults:Background [J]. Ann Intern Med 2001,134 (6):509-17.
    [3]Snow V, Mottur-Pilson C, Cooper RJ, et al. American Academy of Family Pbysicians; American College of Physicians American Society of Internal Medicine; Centers for Disease Control. Principles of appropriate antibiotic use for acute pharyngitis' inadults[J]. Ann Intern Med,2001,134 (6):506-508.
    [4]Royal College of General Practitioners Birmingham Research Unit. Weekly Returns Service Annual Prevalence Report,2007. http://www.rcgp.org.uk/pdf/BRU Annual prevalence report 2007. pdf,2009.3.18.
    [5]Gwaltney JM Jr, Bisno AL. Pharyngitis[M]. In:Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia:Churchill Livingstone.2000,5th ed,1:656-62.
    [6]Poses RM, Cebul RD, Collins M et al. The accuracy of experienced physicians' probability estimates for patients with sore throats:implications for decision making [J]. JAMA,1985,254:925-929.
    [7]Alan L. Bisno. Acute pharyngitis[J]. N Engl J Med,2001,18; 344 (3):205-11.
    [8]杨占秋余宏.临床病毒学[M].中国医药科技出版社,2000,409.
    [9]Pan C., Cheung B.,Tan, S. et al. Genomic signature andmutation trend analysis of pandemic (HIN) 2009 influenza A virus[J]. PLoS One,2010,5:e9549.
    [10]Bautista EChotpitayasunondh T et al. Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (HIN) 2009 Influenza, Clinical aspects of pandemic 2009 influenza A (HIN) virus infection[J]. N Engl J Med,2010,362:1708-1719.
    [11]Marshall S. Giving advice on sore throats [J]. Pharm J,2008,280:127-130.
    [12]Summers A. Sore throats[J]. Accid Emerg Nurs,2005,13:15-17.
    [13]Worrall GJ. Acute sore throat [J]. Can Fam Physician,2007,53:1961-1962.
    [14]Oxford JS, Lambkin R, Gibb I. et al. A throat lozenge containing amylmetacresol and dichlorobenzyl alcohol has a direct virucidal effect on respiratory syncytial virus, influenza A and SARS-CoV[J]. Antivir Chem Chemother,2005,16:129-34.
    [15]Collier L. Human Virology [M]. New York, Oxford J, NY:Oxford University Press,2006.133
    [16]Heikkinen T,Jarvinen A. The common cold[J].Lancet,2003,361:51-59.
    [17]Poses RM,Cebul RD, Collins M. et al. The accuracy of experienced physicians' probability estimates for patients with sore throats:implications for decision making[J]. JAMA,1985,254:925-929.
    [18]Komaroff AL, Pass TM, Aronson MD, et al. The prediction of streptococcal pharyngitis in adults[J]. J Gen Intern Med,1986,1:1-7.
    [19]American Academy of Pediatrics, Committee on Infectious Diseases. Red Book:Report of the Committee on Infectious Diseases.28th ed. Elk Grove Village,I11:American Academy of Pediatrics; 2009.28th ed.313.
    [20]Ebell MH, Smith MA, Barry HC, et al. The rational clinical examination. Does this patient have strep throat?[J] JAMA,2000,284:2912-2918.
    [21]Kaplan EL, Top FH Jr, Dudding BA et al. Diagnosis of streptococcal pharyngitis: differentiation of active infection from the carrier state in the symptomatic child[J]. J Infect Dis,1971,123:490-501.
    [22]Breese BB. A simple scorecard for the tentative diagnosis of streptococcal pharyngitis[J]. Am J Dis Child 1977,131:514-517.
    [23]Wald ER, Green MD, Schwartz B, et al. A streptococcal score card revisited[j]. Pediatr Emerg Care,1998,14:109-11.
    [24]Choby BA. Diagnosis and treatment of streptococcal pharyngitis[J]. Am Fam Physician,2009,79:383-390.
    [25]Gerber MA. Group A streptococcus[C]. In:Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatri.
    [26]Bisno AL, Gerber MA, Gwaltney JM Jr, et al. Diagnosis and management of group A streptococcal pharyngitis:a practice guideline[M] Philadelphia, Pa:Saunders Elsevier; 2007:1135-1139.
    [27]Kellogg JA. Suitability of throat culture procedures for detection of group A streptococci and as reference standards for evaluation of streptococcal antigen detection kits[J]. J Clin Microbiol,1990,28:165-169.
    [28]Shulman ST, Tanz RR, Gerber MA. Streptococcal infections:clinical aspects, microbiology, and molecular pathogenesis[M]. In:Stevens DL, Kaplan EL, eds. Streptococcal pharyngitis. New York:Oxford UniversityPress,2000,76-101.
    [29]Centor RM, Witherspoon JM, Dal ton HP, et al. The diagnosis of strep throat in adults in the emergency room[J]. Med Decis Making,1981,1:239-246.
    [30]Mclsaac WJ, White D, Tannenbaum D, et al. A clinical score to reduce unnecessary antibiotic use in patients with sore throat[J]. Can Med Assoc J,1998,158:75-83.
    [31]McIsaac WJ, Goel V, To T, et al. The validity of a sore throat score in family practice[J]. Can Med Assoc J,2000,163:811-15.
    [32]Dajani A, Taubert K, Ferrieri P, et al. Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever:a statement for health professionals[J]. Pediatrics,1995,96:758-764.
    [33]Group A streptococcal infections[M]. In:Pickering LK, ed.2000 Red book:report of the Committee on Infectious Diseases.. Elk Grove Village,111.:American Academy of Pediatrics,2000,25th ed:526-536.
    [34]C. Pelucchi, L. Grigoryan, C, Galeone et al. Guideline for management of acute sore throat [J]. Clin Microbiol Infect,2012,18 (Suppl.1):1-27.
    [35]WorrallGJ:Acute sore throat [J]. Canadian Family Physician,2007,53(11):1961-1962.
    [36]Neuner JM, Hamel MB, Phillips RS, et al. Diagnosis and management of adults with pharyngitis. A cost-effectiveness analysis[J]. Ann Intern Med,2003,139 (2):113-122.
    [37]Cross S.Rimmer M. Nurse Practitioner Manual of Clinical Skills[M]. London. Bailli ere Tindell.2002:396.
    [38]黄选兆,汪吉宝,孔维佳.实用耳鼻咽喉头颈外科[M].北京:人民卫生出版社,2010,(第2版):314.
    [39]刘渡舟主编.汉·张仲景著.伤寒论校注[M].北京:人民卫生出版社,1991,197.
    [40]明·楼英著.医学纲目[M].北京:中国中医药出版社,1996,292.
    [41]干千主编.干氏耳鼻咽喉口腔科学[M].江苏南京:江苏科学技术出版社,1999,215.
    [42]中华中医药学会.中医耳鼻咽喉科常见病诊疗指南[M].北京:中国中医药出版社,2012,25.
    [43]王士贞主编.中医耳鼻咽喉科学[M].北京:中国中医药出版社,2007,151-156.
    [44]吴敏,贝立民.清解汤治疗急喉痹876例临床观察[J].云南中医中药杂志,1999,20(6):22-23.
    [45]杨建刚.清咽利喉方治疗急性咽炎40例[J].吉林中医药,2001,(4):33.
    [46]黄美珍.利咽汤治疗急性咽炎76例[J].四川中医,2002,20(12):66.
    [47]范宏涛,陈彩云.清咽汤治疗急性咽炎30例临床观察[J].河北中医,2003,2(25):93-95.
    [48]何慈生.牛蒡解肌汤治疗急性咽炎76例[J].中国中医急症,2003,12(4):374.
    [49]苗德远.玄桔射豆重楼汤治疗急性咽炎50例[J].四川中医,2005,23(2):82.
    [50]尹泉,高岩.清咽汤治疗急性咽炎临床验证[J].中国民康医学,2007,19(12):451.
    [51]乔钦才,柴天川,乔钦增,等.“槐枝汤”治疗急性咽炎65例临床观察[J].江苏中医药,2008,40(5):49.
    [52]韩生林.中西医结合治疗急性咽炎56例观察[J].实用中医药杂志,2010,26(3) :174.
    [53]樊治军,徐庆文.六味汤治疗急性咽炎的临床观察[J].中国医药指南,2010,8(22):125-126.
    [54]莫少琪,银翘散加味治疗急性扁桃体炎、咽炎176例.新中医,1995,27(7):50.
    [55]朱亮真.清咽汤治疗急性咽炎52例[J].南京中医药大学学报,2002,18(6):3811.
    [56]张菊.银翘散加味治疗急性咽炎45例疗效观察[J].云南中医中药杂志,2012,33(8):44.
    [57]王瑛.银翘散合增液汤治疗急性咽炎52例[J].山东中医杂志,2003,22(3):151-152.
    [58]李仅波.银翘散加减治疗急性咽炎86例观察[J].社区医学杂志,2007,5(18):29.
    [59]尤丽娟.银翘散加减治疗急性咽炎、扁桃腺炎52例[J].陕西中医,2000,21(6):269.
    [60]孟庆法.中药泡水代茶治疗急性咽炎[J].菏泽医专学报,2003,15(1):96.
    [61]柴峰.清咽润喉胶囊治疗急性咽炎的临床疗效观察[J].中国中西医结合耳鼻咽喉科杂志,1999,7(3):111-112.
    [62]傅南琳,余晓琪,张恩乐.牛黄上清软胶囊治疗急性咽炎的疗效观察[J].中成药,2001,23(5):382-383.
    [63]郭少武,刘进,任大鹏,等.青果片治疗急性咽炎的临床观察[J].辽宁中医杂志,2003,30(5):370.
    [64]秦玉花,朱重光,陈卓昌,等.双黄连含片治疗急性咽炎60例[J].陕西中医,2003,24(5):425-426.
    [65]张念祖,夏立军,穆文清,等.一清胶囊治疗急、慢性咽炎临床观察[J].中国中西医结合耳鼻咽喉科杂志,2003,11(1):34-36.
    [66]郭裕.用咽立爽口含滴丸治疗急性单纯性咽炎效果[J].山东大学基础医学院学报,2005,19(4):227.
    [67]牟宏伟, 陈微.复方瓜子金治疗急性咽炎240例临床总结[J].中国医学杂志,2008,6(3):64-65.
    [68]王建亭,安云芳,赵长青.中药咽疾灵冲剂治疗急性咽炎的临床研究[J].中国中西医结合耳鼻咽喉科杂志,2001,9(4):170-171.
    [69]张嘉庆,李丽,李士瑾.冬凌草片治疗急性咽炎160例临床观察[J].中国中医药现代远程教育,2008,6(2):119.
    [70]陈光远,张瑞明,常静,等.五味沙棘含片治疗急性咽炎的随机对照临床研究[J].华西医学,2002,17(3):295-296.
    [71]秦红鸣,王学勤,易梅,等.美声喉泰含片治疗急喉痹风热证60例评析[J].中医药学刊,2002,20(4):502-503.
    [72]王东方,王勇,孙玲玲,等.蓝芩口服液治疗急性咽炎疗效观察[J].辽宁中医杂志,2005,2(9):916.
    [73]张华,杨晓梅.云南白药为主治疗急喉痹180例[J].时珍国医国药,2006,7(2):259.
    [74]戴建军,宁树成.黄柏胶囊治疗急性和亚急性咽炎100例临床观察[J].实用临床医学,2004,5(4):122.
    [75]杨权生,杨光钦.清热消炎宁胶囊治疗急性咽炎152例[J].中国中医药信息杂志,2003,10 (2):44.
    [76]包剑英.银黄颗粒治疗急性咽炎的临床观察[J].中华医学研究杂志,2005,5(9):924-925.
    [77]李冬莲,蓝玉清.超声雾化吸入鱼腥草治疗急性咽炎200例[J].赣南医学院学报,2005,25(6):876.
    [78]马淙.鱼腥草用于雾化吸入治疗急性咽炎的观察护理[J].中国中西医结合耳鼻咽喉科杂志,2002,10(4):201.
    [79]李冬莲,蓝玉清.超声雾化吸入鱼腥草治疗急性咽炎200例[J].赣南医学院学报,2005,25(6):876.
    [80]郭树繁,贾春芒,张燕,等.肿节风注射液雾化吸入治疗急性咽炎116例[J].吉林中医药,2003,23(7):29.
    [81]张燕平,韩云霞,欧丽.复方肿节风Ⅰ号雾化剂治疗急性咽炎100例[J].陕西中医,2007,28(8):955-956.
    [82]姜莽儿, 陈志凌, 徐世影,等.咽喉灵合剂雾化吸入治疗急性咽炎疗效观察[J].中国中西医结合耳鼻咽喉科杂志,2004,12(6):316-318.
    [83]贺晓琪,周彬,尹玉萍.双黄连超声雾化吸入治疗急性咽炎疗效观察[J].黑龙江医学,2006,30(9):685-686.
    [84]吴希庆,谷雪媛,姚绪民.中药熏治与青霉素治疗急性咽炎疗效观察[J].中国中西医结合耳鼻咽喉科杂志,2001,9(3):141.
    [85]蒋连泓,胡晓惠,应森林,等.中药抗病毒雾化吸入剂治疗上呼吸道感染104例[J].山东中医学院学报,1996,20(3):184-186.
    [86]冯纬纭.咽炎1号合剂含漱治疗急性咽炎105例[J].河北中医,2003,25(2):109.
    [87]朱晓娟,汪东风.咽炎合剂喷雾治疗急性咽炎126例临床观察[J].现代中医药,2003,(4):45.
    [88]刘西长.西瓜霜喷剂治疗急性咽炎的临床观察[J].中国中西医结合耳鼻咽喉科杂志,2002,10(2):96.
    [89]郭裕.咽立爽口含滴丸超声雾化治疗急性单纯性咽炎疗效观察[J].世界临床药物,2006,27(7):431.
    [90]粟栗.复方丹参气雾剂治疗急喉痹30例[J].江苏中医药,2009,41(11):49.
    [91]张孟蕊,毕泗科,张孟颖七味清咽气雾剂治疗急性咽炎120例[J].中医外治杂志,2000,9(1):19-20.
    [92]孙良梅,张名甫,王胜圣等.咽喉宁气雾剂治疗急性咽炎95例[J].吉林中医药,1997,6:21
    [93]柴木,席红.金喉健喷雾剂治疗急性咽炎疗效观察[J].贵阳中医学院学报,1998,20(1):44-45.
    [94]Gwaltney JM Jr, Bisno AL. Pharyngitis. In:Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Vol.
    1. Philadelphia:Churchill Livingstone,2000,5th ed:656-662. [95] Poses RM, Cebul RD, Collins M, et al. The accuracy of experienced physicians' probability estimates for patients with sore throats:implications for decision making[J]. JAMA,1985,254:925-9.
    [96]石钺,石任兵,刘斌,等.银翘散抗流感病毒有效部位群化学成分的分离与鉴定[J].中国中药杂志,2003,28(1):42-47.
    [97]于起福,孙非.四种中草药水煎剂抗柯萨奇B5病毒的细胞学实验研究[J].吉林中医药,1995,(1):35.
    [98]张讳,张汉明,郭美丽.连翘的药理学研究册[J].中国现代应用药学杂志,2000,17(1):7-10.
    [99]Hu KJ(胡克杰),Xu KJ(徐凯建),Wang YH(王跃红),et al. Study of the anfivirus activities of forsythiaside in vitro[J]. Sci-Tech Chin Tradit Med(中国中医药科技),2001,8(2):89.
    [100]蒲秀瑛,梁剑平,王学红,等.贯叶连翘提取物抗甲1型流感病毒活性的研究[J].中草药,2010,41(2):259-264.
    [101]王力川.金银花的化学成分及功效研究进展[J].安徽农业科学,2009,37(5):2036-2037.
    [102]朱述英.金银花化学成分的研究现状[J].价值工程,2011,284-285.
    [103]刘莹,王国丽.金银花提取物对单纯疱疹病毒性角膜炎的作用[J].医药导报,2011,30(11):1421-1424.
    [104]宋健,张会敏,石俊英.金银花防治流感病毒模型血清蛋白组学的初步研究[J].时珍国医国药,2011,22(11):2653-2655.
    [105]胡克杰,孙考祥,王玻璐,等.氯原酸体外杭病毒作用研究[J].哈尔滨医科大学学报,2001,35(6):430-432.
    [106]Nagai T, Morluchi R, Suzuki Y, et al. Mode of action of the anti-Influenza virus activity of plant flavonOld,5,7,4'-trihydroxy-8-methoxyflavone, from the roots of Scutellaria baiealensls[J]. Antiviral Res,1995,26 (1):11.
    [107]Li Y, Ooi LS, Wang H, et al. Antiviral activities of medicinal herbs traditionally used in southern mainland China[J]. Phytother Res,2004,18 (9):718-722.
    [108]张风英,高玉峰,宋鸿儒.黄芩茎叶提取物与生脉饮抗柯萨奇病毒B3的体外研究[J].天津医药,2005,33(11):716-718.
    [109]张道广,Jimmy Kwang,潘胜利.黄芩多糖抗猪生殖和呼吸系统综合征病毒作用的研究[J].时珍国医国药,2005(9):943.
    [110]初正云,初明,滕宇,等. 黄芩苷体内抗流感病毒作用[J]. 中国中药杂志,2007,32(22):2413-2415.
    [111]朱宇同,栖汝才,苏章,等.鱼腥草非挥发油提取物抗病毒作用的初步研究[J].中草 药,1983,14(7):25-26.
    [112]张薇,卢芳国,潘双银,等.鱼腥草中挥发油的提取分析及其抗菌抗病毒作用的研究[J].实用预防医学,2008,15(2):312—316.
    [113]杨子峰,刘妮,黄碧松,等.牛蒡子甙元体内抗甲1型流感病毒作用的研究[J].中药材,2005,28(11):1012-1014.
    [114]杨子峰,王玉涛,秦笙,等. 板蓝根水提物S-03体外抑制甲、乙型流感病毒感染的实验研究[J].病毒学报,2011,27(3):218-223.
    [115]刘盛,陈万生,乔传卓.不同种质板蓝根和大青叶的抗甲型流感病毒作用[J].第二军医大学学报,2002,21(3):204—205.
    [116]左丽,陈丽,唐晓敏,等.黄芪A6组分对流感病毒感染小鼠的防治作用[J].中国病毒学,1997,12(4):342-345.
    [117]盛玲燕,刘家泉.中药治疗单纯疱疹病毒感染分析[J].黑龙江医药,2008,21(4):103-104.
    [118]甄玉珍.大青连翘汤治疗带状疱疹23例[J].山东中医杂志,2008,27(2):824.
    [119]吴成林,杨占秋,侯炜,等.双黄连口服液抗呼吸道合胞病毒的实验研究[J].数理医药学杂志,2005,18(6):592-594.
    [120]邬洪波,李洪梅,长安,等.双黄连分散片抗病毒作用实验研究[J].中国实验方剂学杂志,2004,10(3):48-50.
    [121]莫日根,韩雪梅,新燕,等.蒿芩清胆汤抗流感病毒的实验研究[J].中医研究,2005,18(5):16-18.
    [122]欧敏,董建华,段蕴铀,等.清肺饮对流感病毒感染小鼠免疫功能的调节作用[J].北京中医药大学学报,1998,21(6):19)22.
    [123]马融,王建陵,吴彻,等.防感合剂抗病毒及诱发干扰素的作用观察[J].中国中西医结合杂志,1990,10(4):222-224.
    [124]何建萍.银翘散的临床药理[J].中国实用医药,2009,4(23):149-150.
    [125]潘望望,王雪峰,闰丽娟等.金银花提取物体外抗甲型流感病毒FMI株的研究[J].中国中医药信息杂志,2007,14(6):36-37.
    [126]王雪峰,潘望望,闰丽娟等.牛蒡子提取物体外抗甲型流感病毒FMI株的实验研究[J].中医研究,2007,20(6):18-21.
    [127]肖锦仁,吴红娟,郭星等.不同剂型银翘散抗菌、抗病毒作用的研究[J].湖南中医学院学报,2003,23(1):15-18.
    [128]国家中医药管理局.中华人民共和国中医药行业标准中医病证诊断.南京大学出版社:南京1994.7,125.
    [129]Leland DS, Ginocchio CC. Role of cell culture for virus detection in the age oftechnology[J]. Clin Microbiol Rev,2007,20(1):49-78.
    [130]Cohen J, Powderley WG. Infectious diseases (2nd edition) [J]. Edinburgh UK, Mosby,2004,341-431.
    [131]Seno M, Kanamoto Y, Takao S, et al. Enhancing effect of centrifugation on isolation of influenza virus from clinical specimens[J]. J Clin Microbiol,1990,28 (7):1669-1670.
    [132]Hudson JB, Misra V, Mosmann TR. Cytomegalovirus infectivity:analysis of the phenomenon of centrifugal enhancement of infectivity[J]. Virology,1976,72(1):235-243.
    [133]Diane S, Leland, Christine C, et al.Role of Cell Culture for Virus Detection in the Age of Technology[J].J Clin Microbiol,2007,20 (1):49-78.
    [134]杨子峰,王玉涛莫自耀,等.应用小瓶离心法分离检测2009年1-6月广州市成人流感样病例相关病毒的研究[J].中华检验医学杂志,2010,33(2):132-137.
    [135]Gunson RN, Collins TC, Carman WF. Real-time RT-PCR detection of 12 respiratory viral infections in four triplex reactions[J]. Journal of clinical virology,2005,33 (4):341-344.
    [136]Wang R, ShengZM, Taubenberger JK. Detection of novel (swine origin) H1N1 influenza A virus by quantitative real-time reverse transcription-PCR[J]. Journal of clinical microbiology,2009,47 (8):2675-2677.
    [137]Esposito S, Bosis S, Niesters H, et al. Impact of human coronavirus infections in otherwise healthy children who attended an emergency department [J]. Journal of medical virology,2006,78 (12)-.1609-1615.
    [138]Templeton KE, Scheltinga SA, Beersma MFC, et al. Rapid and Sensitive Method Using Multiplex Real-Time PCR for Diagnosis of Infections by Influenza A and Influenza B Viruses, Respiratory Syncytial Virus, and Parainfluenza Viruses 1,2,3, and 4[J]. Journal of clinical microbiology,2004,42 (4):1564-1569.
    [139]Petit jean J, Vabret A, Dina J, et al. Development and evaluation of a real-time RT-PCR assay on the LightCycler for the rapid detection of enterovirus in cerebrospinal fluid specimens [J]. Journal of clinical virology, the official publication of the Pan American Society for Clinical Virology,2006,35 (3):278-284.
    [140]HeimA, Ebnet C, Harste G, et al. Rapid and quantitative detection of human adenovirus DNA by real-time PCR[J]. Journal of medical virology,2003,70 (2):228-239.
    [141]Lu X, Chittaganpitch M, Olsen SJ, et al. Real-time PCR assays for detection of bocavirus in human specimens [J]. Journal of clinical microbiology,2006,44(9):3231-3235.
    [142]Mclsaac WJ, Goel V, To T,et al.The validity of a sore throat score in family practice[J]. CMAJ,2000,163 (7):811-815.
    [143]Stensballe L, Trautner S, Kofoed PE, et al. Comparison of nasopharyngeal aspirate and nasal swab specimens fordetection of respiratory syncytial virus in different settings in a developing country[J]. Tropical Medicine & International Health,2002,7 (4):317-321.
    [144]Masters HB, Weber KO, Groothuis JR, et al. Comparison of nasopharyngeal washings and swab specimens for diagnosis of respiratory syncytial virus by EIA, FAT, and cell culture[J]. Diagnostic microbiology and infectious disease,1987,8 (2):101-105.
    [145]Ahluwalia G, Embree J, McNicol P, et al. Comparison of nasopharyngeal aspirate and nasopharyngeal swab specimens for respiratory syncytial virus diagnosis by cell culture, indirect immunofluorescence assay, and enzyme-linked immunosorbent assay [J]. Journal of clinical microbiology,1987,25 (5):763-767.
    [146]Covalciuc KA, Webb KH, Carlson CA. Comparison of four clinical specimen types for detection of influenza A and B viruses by optical immunoassay (FLU OIA test) and cell culture methods[J]. Journal of clinical microbiology,1999,37 (12):3971.
    [147]McIntosh K, Hendry RM, Fahnestock M, et al. Enzyme-linked immunosorbent assay for detection of respiratory syncytial virus infection:application to clinical samples[J]. Journal of clinical microbiology,1982,16 (2):329-333.
    [148]Munywoki PK, Hamid F, Mutunga M, et al. Increased detection of respiratory viruses in paediatric outpatients with acute respiratory illness by real-time polymerase chain reaction using nasopharyngeal flocked swabs[J]. Journal of clinical microbiology,2011,49(9):3365-3367.
    [149]Agoritsas K, Mack K, Bonsu BK, et al. Evaluation of the Quidel QuickVue test for detection of influenza A and B viruses in the pediatric emergency medicine setting by use of three specimen collection methods [J]. Journal of clinical microbiology,2006,44 (7):2638-2641.
    [150]Nakajima N, Kitamori Y, Ohnaka S, et al. Development of a Transcription-Reverse Transcription Concerted Reaction Method for Specific Detection of Human Enterovirus 71 from Clinical Specimens[J]. Journal of clinical microbiology,2012,50 (5):1764-1768.
    [151]Legrand L, Vabret A, Dina J, et al. Epidemiological and phylogenic study of human metapneumovirus infections during three consecutive outbreaks in Normandy, France[J]. Journal of medical virology,2011,83 (3):517-524.
    [152]Miller EK, Lu X, Erdman DD, et al. Rhinovirus-associated hospitalizations in young children[J]. Journal of Infectious Diseases,2007,195 (6):773-781.
    [153]Suntarattiwong P, Jarman RG, Levy J, et al. Clinical performance of a rapid influenza test and comparison of nasal versus throat swabs to detect 2009 pandemic influenza A (HIN) infection in Thai children[J]. The Pediatric infectious disease journal,2010, 29 (4):366.
    [154]Stensballe L, Trautner S, Kofoed PE, et al. Comparison of nasopharyngeal aspirate and nasal swab specimens for detection of respiratory syncytial virus in different settings in a developing country[J]. Tropical Medicine and International Health,2002, 7 (4):317-321.
    [155]Moes E, Vijgen L, Keyaerts E, et al. A novel pancoronavirus RT-PCR assay:frequent detection of human coronavirus NL63 in children hospitalized with respiratory tract infections in Belgium[J].BMC Infectious Diseases,2005,5 (1):6.
    [156]Liu WK, Chen DH, Liu Q, et al. Detection of human bocavirus from children and adults with acute respiratory tract illness in Guangzhou, southern China[J]. BMC Infectious Diseases,2011,11 (1):345.
    [157]Midulla F, Scagnolari C, Bonci E, et al. Respiratory syncytial virus, human bocavirus and rhinovirus bronchiolitis in infants[J]. Archives of disease in childhood,2010,95 (1):35-41.
    [158]Chen KF, Rothman RE, Ramachandran P, et al. Rapid identification viruses from nasal pharyngeal aspirates in acute viral respiratory infections by RT-PCR and electrospray ionization mass spectrometry[J]. Journal of virological methods,2011,173 (1):60-66.
    [159]Akmatov MK, Gatzemeier A, Schughart K, et al. Equivalence of Self-and Staff-Collected Nasal Swabs for the Detection of Viral Respiratory Pathogens[J]. PLoS One,2012,7 (11):e48508.
    [160]Loens K, Van Heirstraeten L, Malhotra-Kumar S, et al. Optimal sampling sites and methods for detection of pathogens possibly causing community-acquired lower respiratory tract infections[J]. J Clin Microbiol,2009,47(1):21-31.
    [161]Schultze D, Thomas Y, Wunderli W. Evaluation of an optical immunoassay for the rapid detection of influenza A and B viral antigens[J]. European Journal of Clinical Microbiology and Infectious Diseases,2001,20 (4):280-283.
    [162]Steininger C, Kundi M, Aberle SW, et al. Effectiveness of reverse transcription-PCR, virus isolation, and enzyme-linked immunosorbent assay for diagnosis of influenza A virus infection in different age groups[J]. Journal of clinical microbiology,2002,40 (6): 2051-2056.
    [163]Abu-Diab A, Azzeh M, Ghneim R, et al. Comparison between pernasal flocked swabs and nasopharyngeal aspirates for detection of common respiratory viruses in samples from children[J]. Journal of clinical microbiology,2008,46 (7):2414.
    [164]Hernes S, Quarsten H, Hagen E, et al. Swabbing for respiratory viral infections in older patients:a comparison of rayon and nylon flocked swabs[J]. European Journal of Clinical Microbiology and Infectious Diseases,2011,30 (2):159-165.
    [165]Daley P, Castriciano S, Chernesky M, et al. Comparison of flocked and rayon swabs for collection of respiratory epithelial cells from uninfected volunteers and symptomatic patients[J]. Journal of clinical microbiology,2006,44 (6):2265.
    [166]Moore C, Corden S, Sinha J, et al. Dry cotton or flocked respiratory swabs as a simple collection technique for the molecular detection of respiratory viruses using real-time NASBA[J]. Journal of virological methods,2008,153 (2):84-89.
    [167]Chan K, Peiris J, Lim W, et al. Comparison of nasopharyngeal flocked swabs and aspirates for rapid diagnosis of respiratory viruses in children[J]. Journal of clinical virology,2008,42 (1):65-69.
    [168]Lieberman D, Shimoni A, Keren-Naus A, et al. Identification of respiratory viruses in adults:nasopharyngeal versus oropharyngeal sampling[J]. Journal of clinical microbiology,2009,47 (11):3439.
    [169]Kim C, Ahmed JA, Eidex RB, et al. Comparison of Nasopharyngeal and Oropharyngeal Swabs for the Diagnosis of Eight Respiratory Viruses by Real-Time Reverse Transcription-PCR Assays[J]. PLoS One,2011,6 (6):e21610.
    [170]Tang JW, Ngai KL, Wong JC et al. Emergence of adamantane-resistant influenza,,,A (H3N2) viruses in Hong Kong between 1997 and 2006 [J]. J Med Virol,2008,80(5):895-901.
    [171]杨子峰,关文达,徐国荣,等.2009年广州地区季节性甲型流感病毒对烷胺类药物耐药性分析.中华结核和呼吸杂志,2011,34(2):95-99.
    [172]王志洁,黄铁牛.金银花在体内外抗人Ⅰ型疱疹病毒的实验研究[J].中国中医基础医学杂志,2003,9(7):39-43.
    [173]杜力军,沈映君,国月英,等.银翘散解热机理的研究Ⅲ:银翘散对体外培养单核细胞产生内生致热原的影响[J].中药药理与临床,1992,8(1):8-10.
    [174]刘颖娟,杨占秋,肖红等.中药连翘有效成分体外抗单纯疱疹病毒的实验研究[J].湖北中医学院学报,2004,6(1):36-38.
    [175]谢志平,李洪源,岳晓宏等.甘草抗病毒有效部位体外抗副流感病毒(Ⅲ型)作用的研究[J].中医药信息,2004,24(3):37-39.
    [176]宋秋烨,吴启南,中药淡竹叶的研究进展[J].中华中医药学刊,2007,25(3):526-527.
    [177]耿小茵,刘光太.银翘散治疗病毒性下呼吸道感染疗效观察.[J].海南大学学报自然科学版,2000,18(3):302-303.
    [178]封丽,林寿江.银翘散治疗流行性腮腺炎168例小结[J].口腔医学,1993,131:45.
    [179]刘芳.银翘散治疗病毒性心肌炎52例[J].湖南中医杂志,1997,13()4):29-30.
    [180]李朝霞.中西医结合治疗流行性出血热108例[J].浙江中医杂志,1991,26(7):296.
    [181]齐翠英.中药为主治疗病毒性角膜炎疗效观察[J].河南中医,2002,22(4):45.
    [182]郭元吉,程小雯.流行性感冒病毒及其实验技术,北京,中国三峡出版社,1997:249.
    [183]Robert W. Sidwell, Glen J. Dixon, Sara M. Sellers, et al. In Vivo Antiviral Properties of Biologically Active Compounds[J]. Applied Microbiology,1968, (16) 370-392.
    [184]张增峰.人呼吸道甲型流感病毒受体的分布和感染H5N1流感病毒的病理变化.博士论文.汕头大学,2007.
    [185]Boltz DA, Aldridge JR Jr, Webster RG, etal. Drugs in development for influenza. Drugs, 2010,70 (11):1349-1362.
    [186]李庆国,毕明刚,季宇彬.银翘散对流感病毒感染快速老化小鼠血清中TNF-α及IFN-γ动态表达的影响[J].中国医院用药评价与分析,2009,(1):51-53.
    [187]刘亚娴,李悦,霍炳杰,等.不同煎煮时间银翘散及银翘散加玄参对造模小鼠免疫调节功能的影响[J].河北中医,2010,(2):264-266.
    [188]朱露莎,毕明刚,季宇彬,.等.银翘散对流感病毒FM1感染胸腺缺陷小鼠血清中IFN-γ、IgG含量的影响[J].亚太传统医药,2009,(2):13-15.
    [189]王文丽,王雪峰,闫丽娟,南春红,郝欧美,.银翘散主要药物体外抑制流感病毒作用比较研究[J].中华中医药学刊,2009,(8):1634-1636.
    [190]Galabov, A. S., Simeonova, L., and Gegova, G. Rimantadine and oseltamivir demonstrate synergistic combination effect in an experimental infection with type A
    (H3N2)influenza virus in mice [J]. Antiviral Chemistry and Chemotherapy-Institutional Subscription,2006,17 (5):251-258.
    [191]Govorkova, E. A., Fang, H. B., Tan, M., et al. Neuraminidase inhibitor-rimantadine combinations exert additive and synergistic anti-influenza virus effects in MDCK cells [J]. Antimicrobial Agents and Chemotherapy,2004,48 (12):4855-4863.
    [192]Ilyushina, N. A., Hoffmann, E., Salomon, R., et al. Amantadine-oseltamivir combination therapy for H5N1 influenza virus infection in mice[J]. Antiviral therapy, 2007,12 (3):363.
    [193]Nguyen JT, Smee DF, Barnard DL, et al. Efficacy of Combined Therapy with Amantadine, Oseltamivir, and Ribavirin In Vivo against Susceptible and Amantadine-Resistant Influenza A Viruses[J].PLoS One,2012,7 (1):e31006.
    [194]Zheng BJ, Chan KW, Lin YP, et al.Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus[J].Proc Natl Acad Sci U S A,2008,105 (23):8091.

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