重型甲型H1N1流感的早期预测指标

目的寻求重型甲型H1N1流感患者的早期预测指标。方法比较2009年6月~2010年1月南京地区经RT-PCR确诊的183例普通型和64例重型甲型H1N1流感患者的临床特点及实验室参数,分析重型患者的特征。结果重型外周血白细胞绝对数(6.13±4.06)×109/L,较普通型的(4.48±1.44)×109/L明显偏高(P<0.01);而同期淋巴细胞数(1.23±0.76)×109/L,较普通型(1.50±0.59)×109/L明显下降(P<0.01)。结论除已知的重型甲型H1N1流感指征外,淋巴细胞比例和绝对计数下降可作为重型甲型H1N1患者的早期预测指标。     

热毒宁注射液体外抑制甲型H1N1流感病毒的研究

目的 研究热毒宁注射液体外抑制甲型H1N1流感病毒的作用。方法 以奥司他韦为阳性对照,采用CPE和MTT法观察热毒宁注射液对甲型H1N1流感病毒的抑制作用。结果 CPE法结果表明热毒宁注射液最大无毒浓度（TC₀）为16.2 mg/mL,半数中毒浓度为（TC₅₀）为（24.5±8.1）mg/mL;MTT法测定结果表明热毒宁注射液TC₀为16.2 mg/mL,TC₅₀为（21.7±9.4）mg/mL。热毒宁注射液体外抑制甲型H1N1流感病毒结果显示,CPE法和MTT法热毒宁注射液作用感染细胞1次组半数有效浓度（IC₅₀）为（900.0±173.2）、（933.3±57.7）μg/mL,治疗指数（TI）为27.2、23.2;热毒宁注射液作用感染细胞3次组IC₅₀为（666.7±115.5）、（866.7±208.1）μg/mL,TI为36.7、25.0。结论 热毒宁注射液具有明显体外抗甲型H1N1流感病毒的作用。     

贵州省新型甲型HIN1(2009)流感病毒HA-1基因分析

目的 建立并完善贵州省新型甲型H1N1流感病毒基因分析检测技术平台,了解贵州省新型甲型H1N1(2009)流感病毒HA1片断与WHO公布的流行株有否发生变异.方法 收集16株新型甲型H1N1流感病毒毒株,提取病毒核酸RNA,通过RT-PCR扩增HA1片断,用电泳观察PCR产物目的条带大小,经过纯化、测序,用Biodeit、MEGA4相关软件进行序列比对,同源性及差异性分析,构建系统发育树.结果 贵州省(2009)代表株与中俄代表株A/Habarovak/01/2009 (H1N1)和墨西哥第一株甲型H1N1流感A/Mexio City/001/2009(H1N1)同属一个谱系,亲缘关系较近,同源性在93.2％～95.8％之间.结论 贵州省(2009)代表株与WHO公布的流行株在核苷酸水平上有一定程度的变异.     

人感染H7N9禽流感诊治概况

2013年3月中国上海首先报道了人感染H7N9禽流感病例,这是由上海市公共卫生临床中心应急实验室首先发现,经中国疾病预防控制中心确认的新型重配禽流感病毒H7N9亚型所引起的人感染病例,在患者呼吸道标本中检测到该病毒,该病毒可引起快速进展的重症肺炎及多脏器功能衰竭,3例病例均已死亡。由于这是一种新的病毒引起的禽源性呼吸道传染病,人类所知有限,引起全世界的关注。本文根据已获得的资料,从流行病学、临床表现、诊断与治疗等方面对该新发现的疾病做一介绍。该病在流行病学上有禽类接触史,经呼吸道传播;临床表现为快速进展的重症肺炎、急性呼吸窘迫综合征、多器官功能障碍等;确诊依据是患者呼吸道标本采用RT-PCR检测H7N9禽流感病毒核酸;治疗上尽量在发病48h内首选奥司他韦或扎那米韦抗病毒治疗。     

16例重症感染甲型H_1N_1流感患者药物利用分析

目的:调查分析我院收治的16例重症甲型H1N1流感患者的药物利用情况。方法:采集16例患者病历、及用药记录中疾病诊断和药物治疗相关数据,根据WHO合理用药指标:限定日剂量(DDD)、药物利用指数(DUI)、用药例次数、人均用药费用等回顾性分析评价用药情况。结果:16例重症甲型H1N1流感患者共使用药物128种,其中大输液、抗菌药物、中成药、消化系统药物、循环系统药物,占药品种数64.3%。抗菌药物、激素使用总体合理。奥司他韦疗效确切。结论:针对甲型H1N1流感患者治疗过程中存在的不合理用药现象,迫切需要制定更规范的治疗指南,提高用药安全性与合理性。     

220例甲型H1N1流感病例流行病学调查分析

目的：进一步熟悉、掌握甲型H1N1流感流行病学特点,为预防和控制甲型H1N1流感提供科学依据。方法：回顾分析某定点医院收治的220例甲型H1N1流感病人的相关资料。结果：输入性病例74例,其中境外输入57例;周边地区转诊病例15例,本土病例131例;男109例,女111例;平均年龄19.4&#177;9.3岁;学生183例,占83.2%,以在校集中居住的初高中学生及大学生为多的聚集性群体发病为主,84.1%的患者与甲型H1N1流感疑似或确诊病人接触及感冒病人有明确接触史,潜伏期2.22&#177;0.92d。结论：甲型H1N1流感传染源、传播途径、易感人群3个环节控制难度大。     

奥司他韦治疗疑似甲型H1N1流感的疗效分析

目的观察奥司他韦（达菲）治疗疑似甲型H1N1流感的疗效。方法47例疑似甲型H1NI流感的病例,随机分成治疗组22例和对照组25例,治疗组给予奥司他韦75mg,每天2次口服,疗程5d;对照组给予常规流感对症治疗（感冒灵冲剂）,疗程5～7d。结果治疗组发热缓解时间与流感样症状持续时间均短于对照组,差异均有统计学意义（P〈0．01）。治疗组应用抗生素的比例为25．1％低于对照组的48．3％,差异有统计学意义（P〈0．01）。结论奥司他韦作为抗流感病毒药物治疗疑似甲型H1N1流感安全有效。     

黄金方对流感病毒FM1株感染小鼠肺组织病毒载量及免疫功能的影响

目的:观察黄金方对甲型H1N1流感病毒FM1株感染小鼠肺组织病毒载量I,FN-γ及血清CD 4+/CD 8+比值的影响。方法:采用滴鼻感染流感病毒FM1株建立小鼠肺炎模型,治疗4 d后采用实时荧光定量聚合酶链式反应(RT-PCR)检测肺组织中相对病毒载量,采用双抗体夹心ELISA法测定血清中CD4+和CD 8+含量及肺组织IFN-γ含量。结果:黄金方大、中、小剂量组(6,3,1.5 g.kg-1)均可明显降低感染流感病毒FM1株小鼠肺组织病毒载量,与模型对照组比较有显著性差异(P<0.01,P<0.05),大、中剂量组可明显提高肺组织中IFN-γ水平(与模型对照组比较,P<0.01),中、小剂量组可提高血清CD4+/CD8+比值,与模型对照组比较差异显著(P<0.05)。结论:黄金方在体内对H1N1流感病毒FM1株感染有较好的治疗作用,其治疗作用可能是通过调节免疫功能来实现的。     

In vitro and in vivo efficacy of fluorodeoxycytidine analogs against highly pathogenic avian influenza H5N1, seasonal, and pandemic H1N1 virus infections

Various fluorodeoxyribonucleosides were evaluated for their antiviral activities against influenza virus infections in vitro and in vivo. Among the most potent inhibitors was 2′-deoxy-2′-fluorocytidine (2′-FdC). It inhibited various strains of low and highly pathogenic avian influenza H5N1 viruses, pandemic H1N1 viruses, an oseltamivir-resistant pandemic H1N1 virus, and seasonal influenza viruses (H3N2, H1N1, influenza B) in MDCK cells, with the 90% inhibitory concentrations ranging from 0.13 to 4.6 μM, as determined by a virus yield reduction assay. 2′-FdC was then tested for efficacy in BALB/c mice infected with a lethal dose of highly pathogenic influenza A/Vietnam/1203/2004 H5N1 virus. 2′FdC (60 mg/kg/d) administered intraperitoneally (i.p.) twice a day beginning 24 h after virus exposure significantly promoted survival (80% survival) of infected mice (p = 0.0001). Equally efficacious were the treatment regimens in which mice were treated with 2′-FdC at 30 or 60 mg/kg/day (bid X 8) beginning 24 h before virus exposure. At these doses, 70-80% of the mice were protected from death due to virus infection (p = 0.0005, p = 0.0001; respectively). The lungs harvested from treated mice at day four of the infection displayed little surface pathology or histopathology, lung weights were lower, and the 60 mg/kg dose reduced lung virus titers, although not significantly compared to the placebo controls. All doses were well tolerated in uninfected mice. 2′-FdC could also be administered as late as 72 h post virus exposure and still significantly protect 60% mice from the lethal effects of the H5N1 virus infection (p = 0.019). Other fluorodeoxyribonucleosides tested in the H5N1 mouse model, 2′-deoxy-5-fluorocytidine and 2′-deoxy-2′,2′-difluorocytidine, were very toxic at higher doses and not inhibitory at lower doses. Finally, 2′-FdC, which was active in the H5N1 mouse model, was also active in a pandemic H1N1 influenza A infection model in mice. When given at 30 mg/kg/d (bid X 5) beginning 24 h before virus exposure), 2′-FdC also significantly enhanced survival of H1N1-infected mice (50%, p = 0.038) similar to the results obtained in the H5N1 infection model using a similar dosing regimen (50%, p < 0.05). Given the demonstrated in vitro and in vivo inhibition of avian influenza virus replication, 2′FdC may qualify as a lead compound for the development of agents treating influenza virus infections.     

Immunodepression induced by influenza A virus (H1N1) in lymphoid organs functions as a pathogenic mechanism

In recent years, the frequency of influenza epidemics around the world has posed a great threat to the lives of people, especially those in developing countries. However, it is unclear which organs are the targets of influenza A viruses (IAVs) and what histopathology is caused by IAVs. In this study, BALB/c female mice were infected with H1N1 by nasal inoculation for 5 days. After euthanasia, the brain, heart, lungs, thymus, liver, spleen, hilar lymph nodes, pancreas, kidneys, and adrenal glands were collected. Among these organs, only the lungs, thymus, spleen, and hilar lymph nodes showed lesions. Lung histopathology was characterized by widening of the septum, lymphocyte infiltration, alveolar effusion, and alveolar hyaline membrane formation. The thymus and spleen exhibited atrophy due to the apoptosis of numerous lymphocytes. Although the hilar lymph nodes were enlarged, lymphocyte apoptosis still occurred. The nucleocapsid protein (NP) of IAVs was present not only in the lungs but also in the thymus, spleen, and hilar lymph nodes. In peripheral blood, CD19⁺B lymphocyte levels clearly decreased whileCD3⁺CD8⁺T and CD3⁺CD4⁺T lymphocyte levels temporarily decreased but subsequently increased. These results demonstrate that H1N1 in the lungs could reach lymphoid organs, induce the depletion of B and T lymphocytes in peripheral blood and lymphoid organs, and suppress adaptive immunity.     

甲型H1N1流感肺炎患儿潮气呼吸肺功能的改变

目的探讨甲型H1N1流感肺炎患儿的肺功能变化及其在临床诊断和治疗评估中的意义。方法测定53例甲型H1N1流感肺炎患儿(A组)潮气呼吸肺功能,并与87例同年龄段健康儿童(B组)对照。结果 A组潮气流速-容量环变窄,呼气曲线升枝陡峭,高峰提前,降枝呈波谷样凹陷。与B组比较,A组通气功能指标反映呼气功能障碍,尤其1个月~3岁年龄组患儿(P<0.05)。结论甲型H1N1流感肺炎患儿其急性期肺功能改变主要表现为气道阻塞性通气功能障碍;潮气呼吸肺功能测定可为甲型H1N1流感肺炎患儿评判病情程度及预后评估提供客观依据。     

25例甲型H1N1流感重症及危重症确诊病例临床特征及治疗分析

目的探讨甲型H1N1流感重症及危重症的临床特征和治疗效果。方法动态观察25例确诊甲型H1N1流感重症及危重症病例的临床特征,对诊治情况进行回顾性分析。结果 25例患者中,男11例,女14例,重症9例,危重症16例,25例均发生肺部感染,所有患者均有发热,平均发热持续3.64d入院,咳嗽、乏力、肌肉酸痛、胸闷、恶心等全身症状较多;早期的抗病毒治疗及短期3-7d的小剂量糖皮质激素及晚期的提高免疫力治疗及广谱包括真菌的抗菌药物使用在部分病例中获得成功。结论甲型H1N1流感病毒致病力及致死率与季节性流感相似,重症/危重症需要早期的抗病毒治疗和后期的抗菌治疗及精细的加强治疗以提高存活率。     

甲型H1N1流感患者C反应蛋白和血小板的变化及意义探讨

目的探讨C反应蛋白(CRP)和血小板(PLT)的动态变化在甲型H1N1流感患者中的临床意义。方法回顾性分析我院2009年10月至2010年1月收治的40例符合甲型H1N1流感诊断标准的患者,比较第1、2、3、4天的CRP和PLT变化,分析CRP和PLT与病情预后的关系。结果好转组及恶化组第1天CRP水平差异无统计学意义(P>0.05),第2、3、4天恶化组患者CRP明显高于好转组,差异有统计学意义(P<0.01);好转组PLT均在正常范围,恶化组PLT呈持续下降,两组差异有统计学意义(P<0.05)。结论 RP和PLT的动态变化对判断甲型H1N1流感患者病情预后有重要帮助,CRP水平升高越明显,PLT水平呈持续下降趋势,提示患者病情越重。     

Oseltamivir-resistant pandemic A(H1N1) 2009 influenza viruses detected through enhanced surveillance in the Netherlands, 2009–2010

Enhanced surveillance of infections due to the pandemic A(H1N1) influenza virus, which included monitoring for antiviral resistance, was carried out in the Netherlands from late April 2009 through late May 2010. More than 1100 instances of infection with the pandemic A(H1N1) influenza virus from 2009 and 2010 [A(H1N1) 2009] distributed across this period were analyzed. Of these, 19 cases of oseltamivir-resistant virus harboring the H275Y mutation in the neuraminidase (NA) were detected. The mean 50% inhibitory concentration (IC₅₀) levels for oseltamivir- and zanamivir-susceptible A(H1N1) 2009 viruses were 1.4-fold and 2-fold, respectively, lower than for the seasonal A(H1N1) influenza viruses from 2007/2008; for oseltamivir-resistant A(H1N1) 2009 virus the IC₅₀ was 2.9-fold lower. Eighteen of the 19 patients with oseltamivir-resistant virus showed prolonged shedding of the virus and developed resistance while on oseltamivir therapy. Sixteen of these 18 patients had an immunodeficiency, of whom 11 had a hematologic disorder. The two other patients had another underlying disease. Six of the patients who had an underlying disease died; of these, five had received cytostatic or immunosuppressive therapy. No indications for onward transmission of resistant viruses were found. This study showed that the main association for the emergence of cases of oseltamivir-resistant A(H1N1) 2009 virus was receiving antiviral therapy and having drug-induced immunosuppression or an hematologic disorder. Except for a single case of a resistant virus not linked to oseltamivir therapy, the absence of detection of resistant variants in community specimens and in specimens from contacts of cases with resistant virus suggested that the spread of resistant A(H1N1) 2009 virus was limited. Containment may have been the cumulative result of impaired NA function, successful isolation of the patients, and prophylactic measures to limit exposure.     

老年人接种甲型H1N1流感疫苗不良反应的临床观察

目的：比较季节性流感疫苗与甲型H1N1流感疫苗预防接种后的不良反应。方法：选择我部在前后两个阶段分别接种过季节性流感疫苗与甲型H1N1流感疫苗的离退休老干部及家属106例为观察对象,对观察对象分别在接种时、接种后30min、1h、2h、24h、48h、1周、2周、1个月进行不良反应观察,并统计比较观察结果。结果：季节性流感疫苗组和甲型H1N1流感疫苗组的不良反应均较轻微,且差异无统计学意义（P〉0.05）;季节性流感疫苗组发生常见不良反应4例（3.8%）,甲型H1N1流感疫苗组发生常见不良反应5例（4.7%）,两组均无少见、罕见及极为罕见的不良反应发生。结论：季节性流感疫苗与甲型H1N1流感疫苗的不良反应差异无统计学意义（P〉0.05）,老年人接种甲型H1N1流感疫苗是安全的。     

Progress in structure-based drug design against influenza A virus

Introduction: The 2009-H1N1 influenza pandemic has prompted new global efforts to develop new drugs and drug design techniques to combat influenza viruses. While there have been a number of attempts to provide drugs to treat influenza, drug resistance has been a major problem with only four drugs currently approved by the FDA for its treatment.

Areas covered: In this review, the drug-resistant problem of influenza A viruses is discussed and summarized. The article also introduces the experimental and computational structures of drug targeting proteins, neuraminidases, and of the M2 proton channel. Furthermore, the article illustrates the latest drug candidates and techniques of computer-aided drug design with examples of their application, including virtual in silico screening and scoring, AutoDock and evolutionary technique AutoGrow.

Expert opinion: Structure-based drug design is the inventive process for finding new drugs based on the structural knowledge of the biological target. Computer-aided drug design strategies and techniques will make drug discovery more effective and economical. It is anticipated that the recent advances in structure-based drug design techniques will greatly help scientists to develop more powerful and specific drugs to fight the next generation of influenza viruses.     

磷酸奥司他韦预防甲型H1N1流感时引起不良反应206例报道

目的分析磷酸奥司他韦预防甲型H1N1流感时人群不良反应发生情况。方法对2978例服用磷酸奥司他韦75mg,qd,共7 d预防甲型H1N1型流感者逐日记录其不良反应并将2790例资料完整者进行分析统计。结果 206例出现不良反应,总不良反应发生率为7.38%,以腹泻、恶心、腹痛等消化道症状为主,共157例,发生率为5.62%。皮疹、耳痛、心动过速、食管异物感、鼻出血、失眠等发生率低。结论磷酸奥司他韦预防甲型H1N1流感时不良反应以消化道症状为主,一般不影响治疗。如出现皮疹、心动过速等应停药并给予对症处理。     

退热解毒灵抑制甲型H_1N_1流感病毒的体外实验

目的:观察退热解毒灵水煎剂抑制2009年新型甲型H1N1流感病毒的效果。方法:采用MTT法及细胞病变抑制实验,以利巴韦林为阳性对照,检测退热解毒灵水煎剂对H1N1流感病毒的抑制作用。结果:退热解毒灵水煎剂对体外试验中H1N1流感病毒有一定的抑制作用,其半数中毒质量浓度为8 954.3mg.L-1,抑制H1N1流感病毒的半数有效质量浓度为520.6mg.L-1,治疗指数为17.2。结论:退热解毒灵水煎剂在体外实验中,对H1N1流感病毒有抑制作用。