Effect of Aluminum Hydroxide Adjuvant on the Immunogenicity of the 2009 Pandemic Influenza A/H1N1 Vaccine:Multi-level Modeling of Data with Repeated Measures

Objective To evaluate the effect of the aluminum hydroxide （Al-OH） adjuvant on the 2009 pandemic influenza A/H1N1 （pH1N1） vaccine. Methods In a multicenter, double-blind, randomized, placebo-controlled trial, participants received two doses of split-virion formulation containing 15 ug hemagglutinin antigen, with or without aluminum hydroxide （N-OH）. We classified the participants into six age categories （〉61 years, 41-60 years, 19-40 years, 13-18 years, 8-12 years, and 3-7 years） and obtained four blood samples from each participant on days 0, 21, 35, and 42 following the first dose of immunization. We assessed vaccine immunogenicity by measuring the geometric mean titer （GMT） of hemagglutination inhibiting antibody. We used a two-level model to evaluate the fixed effect of aluminum Al-OH and other factors, accounting for repeated measures. Results The predictions of repeated measurement on GMTs of formulations with or without Al-OH, were 80.35 and 112.72, respectively. Al-OH significantly reduced immunogenicity after controlling for time post immunization, age-group and gender. Conclusion The Al-OH adjuvant does not increase but actually reduces the immunogenicity of the split-virion pH1N1 vaccine.

Cloning of M and NP Gene of H5N1 Avian Influenza Virus and Immune Efficacy of their DNA Vaccines

H5N1 鸟的流行性感冒病毒(A/chicken/Hubei/489/2004 ) 的 M 和 NP 基因被 RT-PCR 从病毒的 RNA 放大，并且分别地克隆向量进 pMD18-T。包含 M 基因(pHM6-m ) 或 NP 基因(pHM6-np ) 的表示 plasmid 然后被把 M 或 NP 基因插入到 pHM6 优核质表示向量构造；构造 plasmid 然后被定序。32 只 BALB/c 老鼠(6-week-old ) 在随机被划分成四个组。三组 BALB/c 老鼠被接种一次有 plasmid pHM6-m， plasmid pHM6-np 的 30 渭 g 或 plasmid pHM6-m (15 渭 g ) 和 pHM6-np (15 渭 g ) 的混合的任何一个 30 渭 g 的肌内的线路分别地。老鼠的一个另外的组作为控制与 100 渭 l PBS 被注射。二个星期以后，所有老鼠与相应 H5N1 鸟的流行性感冒病毒被质问，并且在下列 12 天内观察了。在 pHM6-m 组， pHM6-np 组和混合 plasmids 组的老鼠的幸存率分别地是 62.5% ， 25.0% 和 50.0% 。结果证明有效保护能被 pHM6-m 或 pHM6-np 提供，但是 pHM6-m 比 pHM6-np 提供了更好保护的效果。关键词 H5N1 流行性感冒病毒 - M 基因 - NP 基因 - 克隆 - DNA 疫苗的 CLC 数字 S852.65 基础条款：国家基本科学才能训练资助(NSFC J0630648 )

H5N1 Avian Influenza Pre-pandemic Vaccine Strains in China

Objective To prepare the 4 candidate vaccine strains of H5N1 avian influenza virus isolated in China Methods Recombinant viruses were rescued using reverse genetics. Neuraminidase （NA） and hemagglutinin （HA） segments of the A/Xinjiang/1/2006, A/Guangxi/1/2009, A/Hubei/1/2010, and A/Guangdong/1/2011 viruses were amplified by RT-PCR. Multibasic amino acid cleavage site of HA was removed and ligated into the pCIpoll vector for virus rescue. The recombinant viruses were evaluated by trypsin dependent assays. Their embnjonate survival and antigenicity were compared with those of the respective wild-type viruses. Results The 4 recombinant viruses showed similar antigenicity compared with wild-type viruses, chicken embryo survival and trypsin-dependent characteristics. Conclusion The 4 recombinant viruses rescued using reverse genetics meet the criteria for classification of low pathogenic avian influenza strains, thus supporting the use of them for the development of seeds and production of pre-pandemic vaccines.

Immunogenic and Protective Properties of the First Kazakhstan Vaccine against Pandemic Influenza А(Н1N1) pdm09 in Ferrets

This paper presents the results of a pre-clinical study of the immunogenicity and efficacy of an egg-derived, inactivated, whole-virion adjuvanted vaccine （Refluvac） on ferret models. For this purpose, groups of eight ferrets （6 to 7 months old） were injected with 0.5 mL of vaccine specimens containing 3.75, 7.5 or 15.0 μg of virus hemagglutinin. Administration was intramuscular and given either as a single dose or as two doses 14 days apart. All vaccine specimens manifested immunogenicity in ferrets for single （HI titer, from 51 ± 7 to 160 ± 23） and double （HI titer, from 697± 120 to 829 ± 117） administrations. To assess the protective effects of the vaccine, ferrets from the vaccinated and control groups were infected intranasally with pandemic virus A/California/7/09 （H1N1） pdm09 at a dose of 106 106/0.5 mL. Fourteen days post-infection, the ferrets inoculated with single or double vaccines containing 3.75, 7.5 or 15.0 ~g of hemagglutinin per dose showed no signs of influenza infection, weight loss, or body temperature rise, and no premature deaths occurred. The number of vaccinated ferrets shedding the virus via the upper airway, as well as the amount of virus shed after infection, was significantly reduced in comparison with animals from the control group. Based on our results, we suggest that a single vaccination at a dose of 3.75 or 7.5 μg hemagglutinin be used for Phase I clinical trials.

Stop H5N1 influenza in US cattle now

The relentless march of a highly pathogenic avian influenza virus(HPAIV)strain,known as H5N1,to become an unprecedented panzootic continues unchecked.The leap of H5N1 clade 2.3.4.4b from Eurasia and Africa to North America in 2021 and its further spread to South America and the Antarctic have exposed new avian and mammalian populations to the virus and led to outbreaks on an unrivaled scale.The virus has infected wild birds across vast geographic regions and caused wildlife deaths in some of the world's most biodiverse ecosystems.

Improvement of the efficacy of influenza vaccination (H5N1) in chicken by using extract of Cochinchina momordica seed (ECMS)

Seeds of a Chinese traditional medicine plant, Cochinchina momordica were used in the present study for the improvement of influenza vaccine （HSN 1） in chicken. Crude extraction from Cochinchina momordica seed （ECMS） was obtained by ethanol extraction method. In experiment No. 1, two weeks old chickens were immunized with influenza vaccine （HSN1） alone or combined with ECMS （5, 10, 20, 40 and 80 μg/dose）. Serum IgG antibody levels （by ELISA） as well as effects on dally weight gain were measured on 0, 7, 14 and 28th day after immunization. Results revealed that all ECMS groups numerically increased the antibody levels while 10 and 20 μg/dose groups significantly （P〈0.05） enhanced total IgG antibody on day 28, when compared with control. Average daily weight gain was also significantly higher in 20 μg/dose ECMS group. Adjuvant effect was also confirmed in experiment No. 2 when chickens were immunized with 20 μg/dose ECMS and antibody titer was measured through hemagglutination inhibition （HI）. It is concluded that ECMS has potential to improve the immune responses and deserve further study as an adjuvant.

The interaction between the 2009 H1N1 influenza A hemagglutinin and neuraminidase: mutations, co-mutations, and the NA stalk motifs

As the world is closely watching the current 2009 H1N1 pandemic unfold, there is a great interest and need in understanding its origin, genetic structures, virulence, and pathogenicity. The two surface proteins, hemagglutinin (HA) and neuraminidase (NA), of the influenza virus have been the focus of most flu research due to their crucial biological functions. In our previous study on 2009 H1N1, three aspects of NA were investigated: the mutations and co-mutations, the stalk motifs, and the phylogenetic analysis. In this study, we turned our attention to HA and the interaction between HA and NA. The 118 mutations of 2009 H1N1 HA were found and mapped to the 3D homology model of H1, and the mutations on the five epitope regions on H1 were identified. This information is essential for developing new drugs and vaccine. The distinct response patterns of HA to the changes of NA stalk motifs were discovered, illustrating the functional dependence between HA and NA. With help from our previous results, two co-mutation networks were uncovered, one in HA and one in NA, where each mutation in one network co-mutates with the mutations in the other network across the two proteins HA and NA. These two networks residing in HA and NA separately may provide a functional linkage between the mutations that can impact the drug binding sites in NA and those that can affect the host immune response or vaccine efficacy in HA. Our findings demonstrated the value of conducting timely analysis on the 2009 H1N1 virus and of the integrated approach to studying both surface proteins HA and NA together to reveal their interdependence, which could not be accomplished by studying them individually.

Clinical Predictors for Diagnosing Pandemic (H1N1) 2009 and Seasonal Influenza (H3N2) in Fever Clinics in Beijing,China

Objective Symptomatic predictors of influenza could assess risks and improve decisions about isolation and outpatient treatment. To develop such predictors, we undertook a prospective analysis of pandemic （HIN1） 2009 and seasonal influenza （H3N2） in patients attending fever clinics. Methods From 1 May 2009 to 1 January 2010, all adult patients admitted to fever clinics for suspected influenza, confirmed by real time RT-PCR, were enrolled. Predictors of influenza virus infection were selected with logistic regression models. Measures of sensitivity, specificity, positive and negative likelihood ratios （LRs） were calculated to identify the best predictors. Results The clinical features and routine blood test results of influenza （H1N1） 2009 and seasonal influenza were similar. The positive and negative LRs of current US CDC influenza-like illness （ILl） criteria were modest in predicting influenza infection. Our modified clinic predictors improved the ability of the positive and negative LRs to recognize pandemic （HIN1） 2009 and seasonal influenza. The revised criteria are： fever ~ 38 ~C accompanied by at least one of the following--cough, arthralgia or relative iymphopenia. Conclusion Patients with symptoms and signs that meet the new criteria are likely to have influenza and timely antiviral therapy may be appropriate. In addition, physicians should ascertain if influenza is circulating within the community or if there is a contact history of influenza and combine this information with the newly developed criteria to clinically diagnose influenza.

New mutational trends in the HA protein of 2009 H1N1 pandemic influenza virus from May 2010 to February 2011

As we enter the year of 2011, the 2009 H1N1 pandemic influenza virus is in the news again. At least 20 people have died of this virus in China since the beginning of 2011 and it is now the predominant flu strain in the country. Although this novel virus was quite stable during its run in the flu season of 2009-2010, a genetic variant of this virus was found in Singapore in early 2010, and then in Australia and New Zealand during their 2010 winter influenza season. Several critical mutations in the HA protein of this variant were uncovered in the strains collected from January 2010 to April 2010. Moreover, a structural homology model of HA from the A/Brisbane/10/2010(H1N1) strain was made based on the structure of A/California/04/2009 (H1N1). The purpose of this study was to investigate mutations in the HA protein of 2009 H1N1 from sequence data collected worldwide from May 2010 to February 2011. A fundamental problem in bioinformatics and biology is to find the similar gene sequences for a given gene sequence of interest. Here we proposed the inverse problem, i.e., finding the exemplars from a group of related gene sequences. With a clustering algorithm affinity propagation, six exemplars of the HA sequences were identified to represent six clusters. One of the clusters contained strain A/Brisbane/12/2010(H1N1) that only differed from A/Brisbane/10/2010 in the HA sequence at position 449. Based on the sequence identity of the six exemplars, nine mutations in HA were located that could be used to distinguish these six clusters. Finally, we discovered the change of correlation patterns for the HA and NA of 2009 H1N1 as a result of the HA receptor binding specificity switch, revealing the balanced interplay between these two surface proteins of the virus.

Gene Expression Profiles Comparison between 2009 Pandemic and Seasonal H1N1 Influenza Viruses in A549 Cells

Objective To perform gene expression profiles comparison so that to identify and understand the potential differences in pathogenesis between the pandemic and seasonal A （H1N1） influenza viruses. Methods A549 cells were infected with A/California/07/09 （H1N1） and A/GuangdongBaoan/51/08 （H1N1） respectively at the same MOI of 2 and collected at 2, 4, 8, and 24 h post infection （p.i.）. Gene expression profiles of A549 cells were obtained using the 22 K Human Genome Oligo Array, and differentially expressed genes were analyzed at selected time points. Results Microarrays results indicated that both of the viruses suppressed host immune response related pathways including cytokine production while pandemic H1N1 virus displayed weaker suppression of host immune response than seasonal H1N1 virus. Observation on similar anti-apoptotic events such as activation of apoptosis inhibitor and down-regulation of key genes of apoptosis pathways in both infections showed that activities of promoting apoptosis were different in later stage of infection. Conclusion The immuno-suppression and anti-apoptosis events of pandemic H1N1 virus were similar to those seen by seasonal H1N1 virus. The pandemic H1N1 virus had an ability to inhibit biological pathways associated with cytokine responses, NK activation and macrophage recognition .

Subtle differences in receptor binding specificity and gene sequences of the 2009 pandemic H1N1 influenza virus

A recent phylogenetic inference indicated that the 2009 pandemic H1N1 strains circulating from March 2009 to September 2009 could be divided into two closely related but distinct clusters. Cluster one contained most strains from Mexico, Texas, and California, and cluster two had most strains from New York, both of which were reported to co-circulate in all continents. The same study further revealed nine nucleotide changes in six gene segments of the new virus specific for the two clusters. In the current study, the informational spectrum method (ISM), a bioinformatics technique, was employed to study the receptor binding patterns of the two clusters. It discovered that while both groups shared the same primary human binding affinity, their secondary binding preferences were different. Cluster one favored swine binding as its secondary binding pattern, whereas cluster two mostly exhibited the binding specificity of A/South Carolina/1/18 (H1N1) (one of the 1918 flu pandemic strains) as its secondary binding pattern. Besides all the nine nucleotide changes found in the previous study, Random Forests were applied to uncover several new nucleotide polymorphisms in 10 genes of the strains between the two clusters, and several amino acid changes in the HA protein that might be accountable for the discrepancy of the secondary receptor binding patterns of the two clusters. Finally, entropy analysis was conducted to present a global view of gene sequence variations between the two clusters, which illustrated that cluster one had much higher genetic divergence than cluster two. Furthermore, it suggested a significant overall correspondence between the nucleotide positions of high importance in differentiating the two clusters and nucleotide positions of high entropy in cluster one.

Receptor binding specificity and origin of 2009 H1N1 pandemic influenza virus

Recently, a genetic variant of 2009 H1N1 has become the predominant virus circulating in the southern hemisphere, particularly Australia and New Zealand, and in Singapore during the winter of 2010. It was associated with several vaccine breakthroughs and fatal cases. We analyzed three reported mutations D94N, N125D, and V250A in the HA protein of this genetic variant. It appeared that the reason for D94N and V250A to occur in pairs was to maintain the HA binding to human type receptor, so the virus could replicate in humans efficiently. Guided by this interpretation, we discovered a new mutation V30A that could compensate for N125D as V250A did for D94N. We demonstrated that the presence of amino acids 30A and 125N in HA enhanced the binding to human type receptor, while 30V and 125D favored the receptors of avian type and of A/South Carolina/1/18 (H1N1). Furthermore, a combination of 94D, 125D, and 250V made the primary binding preference similar to that of A/South Carolina/1/18 (H1N1) and a combination of 94N, 125D, and 250A resulted in the primary binding affinity for avian type receptor, which clearly differed from that of A/California/07/2009 (H1N1), a strain used in the vaccine for 2009 H1N1. We also re-examined the origin of 2009 H1N1 to refine our knowledge of this important issue. Although the NP, PA, PB1, and PB2 of 2009 H1N1 were closest to North American swine H3N2 in sequence identity, their interaction patterns were closest to swine H1N1 in North America.

华南地区猪场猪流感和甲型H1N1/2009流感病毒的血清学调查

为了解华南地区猪场猪流感病毒（SIV）和甲型H1N1／2009流感病毒（H1N1pdm09）的流行情况，本研究采用血凝抑制试验（HI），对2013年～2014年从5个省份采集的2208份血清样品进行SIV和H1N1pdm09流感病毒血清学检测，结果显示阳性血清共1269份（57．42％），其中广东省和广西省的感染率最高（p〈0．01）。H1N1SIV、H3N2SIV和H1N1pdm09流感病毒抗体阳性率分别为22．51％、32．97％和26．49％。H1N1pdm09流感病毒的抗体几何平均滴度（GMT）最高（91．93＋1．04，p〈0．05）。H1N1SIV和H3N2SIV在冬季血清阳性率最高，然而在冬末（2月）阳性率却最低（p〈0．01）。H1N1pdm09流感病毒抗体阳性率在5月和9月出现高峰（p〈0．01）。母猪的H1N1SIV和H1N1pdm09流感病毒抗体阳性率高于仔猪和育肥猪，但仔猪的H3N2SIV抗体阳性率却比较高。本研究为华南地区猪场SIV和H1N1pdm09流感病毒的预防提供参考依据。

胶体金免疫层析试剂盒对甲型H1N1流感病毒(2009)抗原快速检测的敏感性分析

目的了解胶体金免疫层析试剂盒对甲型H1N1流感病毒(2009)抗原快速检测的敏感性。方法分别用甲型流感病毒抗原检测试剂盒(胶体金免疫层析法)和甲型/乙型流感病毒抗原检测试剂盒(胶体金免疫层析法)对171例疑似甲型H1N1流感(2009)患者鼻咽拭子标本进行检测,以实时荧光定量聚合酶链反应(FQ-PCR)核酸检测结果为参考,比较胶体金免疫层析试剂盒对不同病程以及不同病毒核酸载量标本检测的敏感性。结果 2种试剂盒的检测敏感性与标本的病毒核酸载量呈正相关(P<0.01),病毒载量≥108拷贝/mL时均可达73.3%。同时,2种试剂盒的阳性检出率与标本的病程呈负相关(P<0.01),发病1～2 d时分别为66.7%和62.5%,推测其在实际应用中的理论敏感性分别可达77.3%和74.6%。结论胶体金免疫层析试剂盒检测甲型H1N1流感病毒(2009)在发病初期及病毒载量较高时有较好的检测效果,可帮助临床早期诊断和海关口岸等机构的现场筛查。但鉴于胶体金免疫层析法自身的局限性,其结果只能作为初步参考,最终的确认结果应以PCR结果为准。

中国流行的2009甲型H1N1猪源流感病毒HA和NA基因的分子和遗传特征

目前流行的甲型H1N1流感病毒是一个复杂的基因重配病毒。对病毒的分子生物学研究,尤其是病毒囊膜蛋白血凝素（haemagglutini,HA）基因和神经氨酸酶（neuraminidase,NA）基因的研究,为控制和预防H1N1流感病毒具有重要的意义。本研究对中国流行的2009甲型H1N1猪源流感病毒的HA和NA基因与疫苗株A/California/07/2009（H1N1）,以及不同国家和地区的病毒株进行核苷酸和氨基酸序列分析。从NCBI的GenBank数据库下载所需要毒株的序列,采用Lasergene 6.0软件包中的EditSeq和MegAlign进行序列分析,进化树分析采用MEGA4.1软件。进化分析表明,中国流行的2009 H1N1流感病毒与疫苗株的核苷酸同源率分别在98.8%~99.7%和98.6%~99.6%之间;裂解位点处为I/VPSIQSR↓G,不具备高致病性流感病毒的特征;有1株NA抗性病毒。尽管与疫苗株相比,中国流行株2009甲型H1N1猪源流感病毒的HA和NA基因有部分突变,但这些突变并不是重要的。本研究首次详细分析了中国流行的2009甲型H1N1猪源流感病毒株与疫苗株的HA和NA基因的分子特征,对实时监测流感病毒HA和NA基因的变化具有重要意义。

福建省2009年甲型H1N1流感病毒NA基因特征及对达菲的耐药性

目的监测福建省甲型H1N1流感病毒NA基因的变化以及对达菲的耐药情况,为临床诊疗和疾病控制提供参考依据。方法从福建省流感监测网络中随机选取23株甲型H1N1流感病毒,经病毒核酸提取和一步法RT-PCR扩增,获得NA基因片段,双向测定核苷酸序列,分析NA基因序列和重要氨基酸位点特征。结果 23株甲型H1N1流感病毒NA片段基因与A/California/07/2009(H1N1)代表株的核苷酸序列进行比较,同源性高达98.1%以上;23株毒株NA蛋白第275位氨基酸均为组氨酸。结论随机选取的23株甲型H1N1流感病毒NA基因片段保持高度同源并且对达菲仍然敏感。随着国内外达菲耐药株的不断出现,应加强耐药性监测,为制定应对甲型H1N1流感流行措施提供参考。

甲型H1N1(2009)流感病毒实时荧光RT-PCR检测方法的建立与评价

自甲型H1N1(2009)流感病毒于2009年在世界多个国家暴发流行后,许多国家的猪群中检测到该病毒的存在,因此建立快速准确的甲型H1N1流感病毒的检测方法成为迫切需求。本研究针对甲型H1N1(2009)流感病毒NA基因设计特异性引物和探针,建立甲型H1N1(2009)流感病毒特异性实时荧光RT-PCR快速检测方法。并将该方法与WHO推荐美国CDC建立的检测方法和美国农业部推荐的检测方法进行比较。通过田间试验验证该方法在实际应用中的效果。结果表明:本研究建立的方法对检测甲型H1N1流感病毒裂解疫苗的灵敏度达到10-6,与WHO推荐的A型流感病毒实时荧光PCR检测方法的灵敏度一致,并且高于美国农业部推荐方法的检测灵敏度(10-5);该方法特异性强,与经典型H1N1和其他亚型流感病毒株无任何交叉反应。与香港兽医化验所进行了检测比对,检测灵敏度和特异性完全一致。近3 800份的田间试验表明,所建立的方法准确可靠。本研究所建立检测方法快速灵敏,检测结果准确可靠,适合用于甲型H1N1(2009)流感病毒的分子生物学检测和监测。

2009甲型H1N1流感流行期间北京急性呼吸道感染儿童常见呼吸道病毒的研究

目的了解2009至2010年甲型H1N1流感大流行期间北京地区急性呼吸道感染患儿中,除流感病毒外的其他几种常见呼吸道病毒感染的流行情况。方法设计并建立检测包括呼吸道合胞病毒(RSV)A/B亚型,副流感病毒(PIV)1、2、3型,腺病毒(ADV)和人博卡病毒(HBoV)在内的多重实时荧光PCR方法,并应用该方法对2009年6月至2010年2月甲型H1N1流感大流行期间,对首都儿科研究所附属儿童医院就诊的急性呼吸道感染患儿中甲型H1N1流感病毒检测阴性的咽拭子标本进行上述呼吸道病毒的核酸检测。结果新建立的多重RT-PCR方法最低可检测的目标基因含量为10～300拷贝数,未见与其他非目标病毒的交叉反应。本研究共检测标本849份,病毒检测总阳性率为39.0%(331份),5岁以下占87.6%(290/331份)。各病毒的检测阳性率分别为RSV-A亚型1.4%(12份),RSV-B亚型8.4%(71份),PIV-1型8.2%(70份),PIV-2型0.5%(4份),PIV-3型3.9%(33份),ADV13.9%(118份),HBoV2.7%(23份)。RSV检出以B亚型为主(85.5%),流行高峰在2009年11月至2010年2月。PIV检出以PIV-1型及PIV-3型为主,PIV-1型的流行高峰在2009年7月至2009年10月,PIV-2型及PIV-3型的流行高峰在2009年6～9月。ADV病毒在研究期间均有较高检出率(平均为13.9%),HBoV的流行高峰在2009年9～12月。结论除流感病毒外,ADV、RSV-B及PIV可能也是2009甲型H1N1流感流行期间引起儿童急性呼吸道感染的重要病原。比较以往的资料可见各病原在2009甲型H1N1流感流行期间的流行季节性及检出率基本未受到新型流感病毒的影响。

南北方2009年新型甲型H1N1流感中医证素分布特征分析

目的了解南北方2009年新型甲型H1N1流感中医证候要素的分布规律及证候研究现状。方法检索中国知网数据库、万方数据库发表的研究时间在流感大流行期间（2009年5月至2010年8月）,西医诊断依据《甲型H1N1流感治疗方案》（1~4版）,具有明确的证候分型文献共30篇,总结、分析各文献的文献类型、证候诊断标准、研究场所、研究对象、证候分型、临床症状等方面的内容,并对规范化后的证候分型进行证素拆分。结果总结流感大流行期间症状25个,提取病位证素7个,病性证素9个。病位证素主要在肺、卫分,其次是表、气分,其中北方肺、卫分的比例更大些,南方也是肺卫最常见,但表、气分的比例相对大些。病性证素以热、疫毒、（外）风为主,（外）寒、湿亦可见,痰、气虚、阴虚则较为少见,其中北方以风热疫毒为主,南方在感受风热疫毒的同时,（外）寒、湿温的比例相对较高。结论从文献报道来看,2009年新型H1N1流感以风热疫毒侵袭肺卫为主;北方以风热疫毒为主,卫表较轻,肺热较重;南方在感受风热疫毒的同时,兼见（外）寒、湿之邪。

2009年的甲流H1N1

为了及时控制甲型H1N1流感的危害。本刊本期起选登甲型流感的专家论坛、论著、呼吸病研究、病例报告、护理等有代表性的稿件,陆续给予优先刊出,供读者们参阅。