Can Toll-Like Receptor (TLR) 2 be considered as a new target for immunotherapy against hepatitis B infection?

The current literature describes pivotal mechanisms in which hepatitis B virus (HBV) induces liver diseases including inflammation, cirrhosis and hepatocellular carcinoma (HCC). It appears that differences in genetic and immunological parameters between patients and controls may be responsible for inducing the prolonged forms of the infection. Previous studies demonstrated that Toll-Like Receptors (TLRs) play key roles in viral recognition and inducing appropriate immune responses. Therefore, TLRs can be considered as key sensors for HBV recognition and subsequent induction of immune responses against this virus. It has also been shown that the TLR2 detects several microbial PAMPs either in its homodimer form or in a heterodimer with TLR1 or TLR6 and subsequently activates NF-κB in a MYD88 dependent manner. Therefore, defective TLR2 expression may result in impaired immune responses against HBV which is reported in long-term forms of hepatitis B. This review presents the recent data regarding the status and important roles played by TLR2 in HBV recognition and induction or suppression of immune responses against HBV as well as its roles in the pathogenesis of cirrhosis and HCC in prolonged hepatitis B forms.     

基于胸部CT影像学表现的肺部感染病原体的评估和甑别

肺部感染是最常见的感染性疾病,早期快速、准确的病原学诊断、精准治疗是改善肺部感染预后、降低死亡率的关键。不少特定病原体引起的肺部感染病灶,在胸部CT表现具体一定的特征。根据病灶形态、大小、数量、变化速度,可评估和甑别引起肺部感染可能的病原体。本文介绍肺部感染相关的胸部CT常见和重要的影像学特征,以提升临床医生对评估肺部感染病原体、合理使用抗菌药物和改善肺部感染预后的能力和重视。     

多重PCR检测方法在儿童流感样病例病原检测中的临床价值（附94例报告）

目的　探讨多重聚合酶链反应（PCR）检测方法在儿童流感样病例病原检测中的临床应用价值,了解儿童流感样病例病原情况。方法　收集2018年11月至2019年2月北京地区94例儿童流感样病例咽拭子标本,采用多重PCR核酸检测技术测定甲型流感病毒（InfA）、 甲型流感病毒H1N1（InfA-H1N1）、 甲型流感病毒H3N2（InfA-H3N2）、 乙型流感病毒（InfB）、 人副流感病毒、 呼吸道合胞病毒（RSV）、 人腺病毒（HADV）、 人鼻病毒（HRV）、 人博卡病毒、 人偏肺病毒（HMPV）、 人冠状病毒（HCoV）和肺炎支原体（MP）、 衣原体13种病原核酸。结果　94例标本中78例（82.98%）可测出病原,其中69例（73.40%）检出1种病原,9例（9.57%）检出2种病原; 94例标本中52例（55.32%）检出流感病原,26例（27.66%）检出非流感病原。单一病原检出由多到少为InfA-H1N1 31例,InfA-H3N2 10例,RSV 9例,HMPV 7例,InfA、 HRV、 HADV各3例,InfB、 HCoV及MP各1例。9例检出2种病原的标本中,6例检出流感分别合并其他病毒（HRV、 HADV、 RSV、 HCoV、 HMPV）,1例检出甲流H1N1和H3N2,2例分别检出RSV、 HRV及HCoV、 HADV。结论　非流感病原微生物引起流感样病例并不少见,多重PCR检测有助于全面了解流感样病例的病原和混合感染情况。     

肺炎1号方的组方思路及理论创新

认为广东地区新型冠状病毒肺炎(简称"新冠肺炎")是以热毒为基本属性的疫疠之气所致,从发病季节及病邪性质看,可归属于温邪为主的疫疠范畴,可称之为"风温""温热疫".基于对广东地区新冠肺炎病因、病机的认识,分析肺炎1号方的组方思路与在清热解毒、透邪清宣及止咳化痰的同时使用益气养阴的理论创新点,为积极开展中医药救治新冠肺炎及...     

从风论治室性早搏

室性早搏属中医"心悸"范畴,其发病特点与中医"风证"有相似之处."风为百病之长",外风、内风均可导致室性早搏的发生.外风可由表及里或直中于心而发病,多伴有表证,治疗上应注重风药的使用;内风多由热极生风、痰热生风、肝风内动、血虚生风、阴虚动风等扰动心神而发病,在清热、化痰、平肝、养血、滋阴的基础上,亦当注重祛风熄风."邪...     

基于伏邪理论从“寒热-痰瘀-虚劳”角度分期辨治肺痿

肺痿是以肺叶痿弱为特征的慢性肺脏虚损性疾病,以咳唾涎沫、气短为主症,与现代医学特发性肺纤维化（IPF）相类似。临床以咳嗽、进行性呼吸困难、喘促胸闷为主要表现,甚则呼吸衰竭危及生命。肺痿属于古代疑难杂症,现代医学治疗亦十分棘手。汉代张机从“寒热-痰瘀-虚劳”的角度阐述了肺痿的主要病机,开创了治疗肺痿之先河。肺痿的病因病机复杂多样,病情迁延难愈,与伏邪理论“伏而不发”的特点不谋而合。因此,基于伏邪理论,结合中西医病机特点,进一步探讨肺痿早期、进展期、终末期3个阶段的分期论治思路,以期为肺痿不同阶段论治提供新的辨证论治思路。     

气管切开与非气管切开患者肺部感染病原菌分布及耐药率比较分析

目的 探讨气管切开与非气管切开患者肺部感染的病原菌分布及耐药率。方法 收集2014年1~12月中国人民解放军海军总医院高压氧科气管切开与非气管切开肺部感染患者的送检痰标本,采用法国梅里埃全自动微生物分析仪进行菌种鉴定和药物敏感性试验,对其病原菌分布及耐药率进行比较。结果 气管切开患者的肺部感染检出病原菌前10位依次为铜绿假单胞菌、鲍曼不动杆菌、奇异变形杆菌、肺炎克雷伯菌、黏质沙雷菌、大肠埃希菌、金黄色葡萄球菌、白色假丝酵母菌、表皮葡萄球菌和溶血葡萄球菌,分别占25.3%、13.8%、12.8%、11.7%、11.1%、8.2%、5.9%、5.6%、1.7%和1.5%;非气管切开患者的检出病原菌前10位依次为鲍曼不动杆菌、铜绿假单胞菌、白色假丝酵母菌、溶血葡萄球菌、肺炎克雷伯菌、恶臭假单胞菌、大肠埃希菌、热带假丝酵母菌、金黄色葡萄球菌和表皮葡萄球菌,分别占21.1%、20.5%、15.1%、12.9%、6.0%、5.8%、4.7%、4.1%、3.3%和3.3%。铜绿假单胞菌在气管切开患者中对头孢哌酮/舒巴坦较为敏感,而在非气管切开患者中对多黏菌素B较为敏感,耐药率都小于25.0%;所有患者均出现耐亚胺培南铜绿假单胞菌(IRPA)。鲍曼不动杆菌的耐药率均较高,但在气管切开患者中,阿米卡星、多黏菌素B、左氧氟沙星的耐药率稍低。气管切开与非气管切开患者中真菌感染均以白色假丝酵母菌居首位,但非气管切开患者中真菌类型和感染率较高。结论 气管切开与非气管切开患者的肺部感染病原菌分布和耐药率有明显区别,临床应根据药敏合理使用抗菌药物,加强呼吸道管理,防止医院感染,以利于肺部感染控制。     

Structural and functional analysis of de‐N‐acetylase PgaB from periodontopathogen Aggregatibacter actinomycetemcomitans

The oral pathogen Aggregatibacter actinomycetemcomitans uses pga gene locus for the production of an exopolysaccharide made up of a linear homopolymer of β‐1,6‐N‐acetyl‐d ‐glucosamine (PGA). An enzyme encoded by the pgaB of the pga operon in A. actinomycetemcomitans is a de‐N‐acetylase, which is used to alter the PGA. The full length enzyme (AaPgaB) and the N‐terminal catalytic domain (residues 25–290, AaPgaBN) from A. actinomycetemcomitans were cloned, expressed and purified. The enzymatic activities of the AaPgaB enzymes were determined using 7‐acetoxycoumarin‐3‐carboxylic acid as the substrate. The AaPgaB enzymes displayed significantly lower de‐N‐acetylase activity compared with the activity of the deacetylase PdaA from Bacillus subtilis, a member of the CE4 family of enzymes. To delineate the differences in the activity and the active site architecture, the structure of AaPgaBN was determined. The AaPgaBN structure has two metal ions in the active site instead of one found in other CE4 enzymes. Based on the crystal structure comparisons among the various CE4 enzymes, two residues, Q51 and R271, were identified in AaPgaB, which could potentially affect the enzyme activity. Of the two mutants generated, Q51E and R271K, the variant Q51E showed enhanced activity compared with AaPgaB, validating the requirement that an activating aspartate residue in the active site is essential for higher activity. In summary, our study provides the first structural evidence for a di‐nuclear metal site at the active site of a member of the CE4 family of enzymes, evidence that AaPgaBN is catalytically active and that mutant Q51E exhibits higher de‐N‐acetylase activity.