祛风通络、清热凉血法治疗单纯型过敏性紫癜临床观察

目的观察祛风通络、清热凉血法治疗单纯型过敏性紫癜的疗效,及其对细胞、体液免疫功能的影响。方法将60例单纯型过敏性紫癜患者随机分为治疗组与对照组,每组30例。治疗组接受祛风通络、清热凉血中药治疗,对照组接受西医基础治疗,均连续治疗14d。治疗前后分别观察两组临床疗效及外周血T细胞亚群及血清免疫球蛋白水平。结果两组患者治疗后外周血CD4+T细胞比例,CD4+/CD8+比值以及血清IgG水平均较治疗前显著升高(P<0.01),CD8+T细胞比例和血清IgA、IgM水平均较治疗前显著降低(P<0.01);在这些指标的改善方面,治疗组均显著优于对照组(P<0.01)。结论祛风通络、清热凉血法对单纯型过敏性紫癜具有较好的临床疗效,其机制与调节患者免疫功能有关。     

Rapid generation of pandemic influenza virus vaccine candidate strains using synthetic DNA

Please cite this paper as: Verity et al. (2011) Rapid generation of pandemic influenza virus vaccine candidate strains using synthetic DNA. Influenza and Other Respiratory Viruses DOI:10.1111/j.1750‐2659.2011.00273.x. Background Vaccination is considered the most effective means of reducing influenza burden. The emergence of H5N1 and pandemic spread of novel H1N1/2009 viruses reinforces the need to have strategies in place to rapidly develop seed viruses for vaccine manufacture. Methods Candidate pandemic vaccine strains consisting of the circulating strain haemagglutinin (HA) and neuraminidase (NA) in an A/PR/8/34 backbone were generated using alternative synthetic DNA approaches, including site‐directed mutagenesis of DNA encoding related virus strains, and rapid generation of virus using synthetic DNA cloned into plasmid vectors. Results Firstly, synthetic A/Bar Headed Goose/Qinghai/1A/2005 (H5N1) virus was generated from an A/Vietnam/1194/2004 template using site‐directed mutagenesis. Secondly, A/Whooper Swan/Mongolia/244/2005 (H5N1) and A/California/04/09 (H1N1) viruses were generated using synthetic DNA encoding the viral HA and NA genes. Replication and antigenicity of the synthetic viruses were comparable to that of the corresponding non‐synthetic viruses. Conclusions In the event of an influenza pandemic, the use of these approaches may significantly reduce the time required to generate and distribute the vaccine seed virus and vaccine manufacture. These approaches also offer the advantage of not needing to handle wild‐type virus, potentially diminishing biocontainment requirements.     

Efficacy of a heterologous vaccine and adjuvant in ferrets challenged with influenza virus H5N1

Please cite this paper as: Vela et al. (2012) Efficacy of a heterologous vaccine and adjuvant in ferrets challenged with influenza virus H5N1. Influenza and Other Respiratory Viruses 6(5), 328–340. Background In 1997, highly pathogenic avian influenza (HPAI) viruses caused outbreaks of disease in domestic poultry markets in Hong Kong. The virus has also been detected in infected poultry in Europe and Africa. Objective The objective of this study was to determine the efficacy of a heterologous vaccine administered with and without the aluminum hydroxide adjuvant in ferrets challenged with HPAI (A/Vietnam/1203/04). Methods Animals in four of the five groups were vaccinated twice 21 days apart, with two doses of a heterologous monovalent subvirion vaccine with or without an aluminum hydroxide adjuvant and challenged with a lethal target dose of A/Vietnam/1203/04. Results All animals vaccinated with the heterologous vaccine in combination with the aluminum hydroxide adjuvant survived a lethal challenge of A/Vietnam/1203/04. Four of the eight animals vaccinated with 30 μg of the vaccine without the adjuvant survived, while two of the eight animals vaccinated with 15 μg of the vaccine without the adjuvant survived. None of the unvaccinated control animals survived challenge. Additionally, changes in virus recovered from nasal washes and post‐mortem tissues and serology suggest vaccine efficacy. Conclusions Altogether, the data suggest that the heterologous vaccine in combination with the aluminum hydroxide adjuvant offers maximum protection against challenge with A/Vietnam/1203/04 when compared to the unvaccinated control animals or animals vaccinated without any adjuvant.     

Characteristics of Li‐Fraumeni syndrome in Japan: A review study by the special committee of JSHT

Li‐Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome, and the majority of patients with LFS have been identified with germline variants in the p53 tumor suppressor (TP53) gene. In the past three decades, considerable case reports of TP53 germline variants have been published in Japan. To the best of our knowledge, there have been no large‐scale studies of Japanese patients with LFS. In this study, we aimed to identify Japanese patients with TP53 germline variants and to reveal the characteristics of LFS in Japan. We collected reported cases by reviewing the medical literature and cases diagnosed at the institutions of the authors. We identified 68 individuals from 48 families with TP53 germline pathogenic or likely pathogenic variants. Of the 48 families, 35 (72.9%) had missense variants, most of which were located within the DNA‐binding loop. A total of 128 tumors were identified in the 68 affected individuals. The 128 tumor sites were as follows: breast, 25; bones, 16; brain, 12; hematological, 11; soft tissues, 10; stomach, 10; lung, 10; colorectum, 10; adrenal gland, 9; liver, 4; and others, 11. Unique phenotype patterns of LFS were shown in Japan in comparison with those in a large national LFS cohort study in France. Above all, a higher frequency of patients with stomach cancer was observed in Japanese TP53 germline variant carriers. These results may provide useful information for the clinical management of LFS in Japan.     

MSH2 c.1022T>C,p.Leu341Pro is a founder pathogenic variation and a major cause of Lynch syndrome in the North of France

Interpretation of missense variants remains a major challenge for genetic diagnosis, even in well‐known genes such as the DNA‐mismatch repair (MMR) genes involved in Lynch syndrome. We report the characterization of a variant in MSH2: c.1022T>C, which was identified in 20 apparently unrelated families living in the North of France. A total of 150 patients from 20 families were included in this study. Family segregation studies, tumor analyses and functional analyses at both the RNA and protein levels were performed. Founder effect was evaluated by haplotype analysis.We show that MSH2 c.1022T>C is a missense variant (p.Leu341Pro) that affects protein stability. This variant is frequent in the North of France (7.7% of pathogenic variations identified in MMR genes), and is located on an ancestral haplotype. It is associated with a high risk of a broad tumor spectrum including brain and cutaneous cancers. The MSH2 c.1022T>C variant is a pathogenic founder variation associated with a high risk of cancer. These findings have important implications for genetic counseling and management of variant carriers.     

A substantial proportion of apparently heterozygous TP53 pathogenic variants detected with a next‐generation sequencing hereditary pan‐cancer panel are acquired somatically

Previous analysis of next‐generation sequencing (NGS) hereditary pan‐cancer panel testing demonstrated that approximately 40% of TP53 pathogenic and likely pathogenic variants (PVs) detected have NGS allele frequencies between 10% and 30%, indicating that they likely are acquired somatically. These are seen more frequently in older adults, suggesting that most result from normal aging‐related clonal hematopoiesis. For this analysis, apparent heterozygous germline TP53 PV carriers (NGS allele frequency 30–70%) were offered follow‐up testing to confirm variant origin. Ninety‐eight probands had samples submitted for follow‐up family member testing, fibroblast testing, or both. The apparent heterozygous germline TP53 PV was not detected in 32.6% (15/46) of submitted fibroblast samples, indicating that it was acquired somatically, either through clonal hematopoiesis or via constitutional mosaicism. Notably, no individuals with confirmed germline or likely germline TP53 PVs met classic Li–Fraumeni syndrome (LFS) criteria, only 41% met Chompret LFS criteria, and 59% met neither criteria, based upon provider‐reported personal and family cancer history. Comprehensive reporting of TP53 PVs detected using NGS, combined with follow‐up analysis to confirm variant origin, is advised for clinical testing laboratories. These findings underscore the investment required to provide individuals and family members with clinically accurate genetic test results pertaining to their LFS risk.     

Fabry disease caused by the GLA p.Phe113Leu (p.F113L) variant: Natural history in males

Background, aims and methodsThe α-galactosidase gene (GLA) c.337T>C/p.Phe113Leu variant was originally described in patients with late-onset cardiac forms of Fabry disease (FD), who had residual α-galactosidase activity. It has since emerged as the most commonly reported GLA variant in Portuguese subjects diagnosed with FD but is also prevalent in the Italian population, where two boys carrying the GLA Leu113 allele were identified in a large-scale newborn screening program, the variant allele segregating in both cases with the same surrounding haplotype. To further delineate the genotype-phenotype correlations of this GLA variant, we have reviewed the natural history and clinical phenotypes of 11 symptomatic Portuguese males, from 10 unrelated families originating from several different areas in mainland Portugal and Madeira Island, who were diagnosed with FD associated with the GLA Leu113 allele in a diversity of clinical and screening settings. Nine of the patients were the probands of their respective families. To test whether the GLA Leu113 allele inherited by the 10 Portuguese and the two Italian families resulted from independent mutational events, we have additionally performed a haplotype analysis with 5 highly polymorphic, closely linked microsatellite markers surrounding the GLA gene.Results and conclusionsHemizygosity for the GLA Leu113 variant allele is associated with a late-onset form of FD, invariably presenting with severe cardiac involvement. Clinically relevant cerebrovascular and kidney involvement may also occur in some patients but the pathogenic relationship between the incomplete α-galactosidase deficiency and the risks of stroke and of chronic kidney disease is not straightforward. The observation that the Leu113 allele segregated within the same GLA microsatellite haplotype in both the Portuguese and Italian families suggests its inheritance from a common ancestor.     

四川省绵阳市2015—2018年手足口病流行特征

目的 分析四川省绵阳市2015—2018年手足口病的流行病学特征,为今后手足口病防控工作提供科学依据。方法 通过中国疾病预防控制信息系统收集绵阳市2015—2018年手足口病数据进行描述性流行病学分析。结果 2015—2018年共报告手足口病病例18 573例,年平均发病率为97.32/10万,重症病例54例,占病例总数的0.29%;病例主要集中在4—7月和10—11月,分别占病例总数的40.85%（7 587例）和32.52%（6 040例）。病例年龄主要集中在5岁以下儿童,共报告17 957例（占96.68%）,其中1~3岁组尤为突出（16 223例,占87.35%）;职业分布以散居儿童为主,共报告12 213例,占总病例的65.76%;男性11 003例,女性7 570例,男女比例为1.45∶1,男性发病率高于女性。病原学监测结果显示,2015—2018年绵阳市共检出肠道病毒阳性标本4 690份,肠道病毒71型（EV71）、柯萨奇病毒 A16 型（CoxA16）和其他肠道病毒构成比分别为10.77%、25.67%、63.56%。各年份不同类型病原构成比差异有统计学意义（χ²=1 288.125,P<0.01）。结论 绵阳市2015—2018年手足口病呈隔年高发流行态势,总体呈双峰的季节分布,5岁以下儿童为主要发病人群,重症发生率逐年下降,不同年份优势毒株有所变化。应加强病原学监测,加强重点地区、重点人群的防控。     

基于夏桂成改邪养正观探讨重建RVVC患者阴道微生态的辨治思路与方法

复发性外阴阴道假丝酵母菌病（RVVC）较难治愈,常反复发作,病程缠绵。国医大师夏桂成教授团队基于改邪养正学术观点,以分消走泄为基本治法,调理阴道整体内环境为立足点,重建阴道微生态为基础,扶植优势菌群如乳酸杆菌等的恢复,从而纠正局部免疫微环境的失调,发挥治愈疾病的目的,并研发了加味二妙颗粒用于临床治疗。      

老年患者医院获得性肺炎的病原菌耐药性分析

目的:了解县级医院老年患者医院获得性肺炎的病原菌种类分布及耐药特征,为临床科室预防与治疗老年患者医院获得性肺炎选择抗生素提供参考指南。方法:对255例年龄≥60岁的获得性肺炎患者原始病历进行逐份查阅统计;痰液或下呼吸道吸取物的无菌采集、细菌培养、种型鉴定按照临床微生物检验的技术路线进行实验操作;药敏检测采用WHO规定的KB法,抑菌圈测量,敏感、中介、耐药数据比照CLSI最新规则评价;数据统计学采用WHONET 5.6软件处理,实验条件遵照室内质量控制条例进行标准化管理。结果:279株病原菌中,位于前6位的细菌是:肺炎克雷伯菌(24.7%)、铜绿假单胞菌(15.4%)、金黄色葡萄球菌(14.7%)、鲍曼不动杆菌(13.3%)、白色假丝酵母菌(7.5%)、大肠埃希菌(5.7%)。药物检测发现:大部分病原菌对临床抗菌药物产生了严重的抗药性:MRSA检出率为46.3%,产ESBLs大肠埃希菌和肺炎克雷伯菌检出率为47.1%,耐亚胺培南铜绿假单胞菌和鲍曼不动杆菌分别达到25.6%、32.4%;革兰阴性杆菌耐药率20%的抗菌药物有阿米卡星、头孢哌酮/舒巴坦,耐药率最高的是磺胺甲噁唑/甲氧苄啶,均65%;但肠杆菌科菌株对碳青霉烯类药物100%敏感;金黄色葡萄球菌对糖肽类药物100%敏感。结论:老年患者医院获得性肺炎的病原菌耐药性上升趋势明显,务必采取有效的治理措施,严格医师抗生素处方管理,致力于改变细菌耐药性快速上升的不良现象。