A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.     

热疗对肿瘤免疫微环境中免疫细胞及免疫相关细胞因子的影响

随着对肿瘤热疗和肿瘤免疫微环境(TIME)的深入研究,近年来热疗对TIME的作用越来越受到学者们的重视。本文就目前国内外研究进展,对热疗与TIME中几类主要免疫细胞和免疫相关细胞因子的影响及作用机制作一综述。全面而透彻的了解热疗对TIME的调控作用,有助于为肿瘤治疗提供新的思路和方法。     

Isolated Donor Specific Alloantibody-Mediated Rejection after ABO Compatible Liver Transplantation

Antibody-mediated rejection (AMR) after liver transplantation is recognized in ABO incompatible and xeno-transplantation, but its role after ABO compatible liver transplantation is controversial. We report a case of ABO compatible liver transplantation that demonstrated clinical, serological and histological signs of AMR without evidence of concurrent acute cellular rejection. AMR with persistently high titers of circulating donor specific antibodies resulted in graft injury with initial centrilobular hepatocyte necrosis, fibroedematous portal expansion mimicking biliary tract outflow obstruction, ultimately resulting in extensive bridging fibrosis. Immunofluorescence microscopy demonstrated persistent, diffuse linear C4d deposits along sinusoids and central veins. Despite intense therapeutic intervention including plasmapheresis, IVIG and rituximab, AMR led to graft failure. We present evidence that an antibody-mediated alloresponse to an ABO compatible liver graft can cause significant graft injury independent of acute cellular rejection. AMR shows distinct histologic changes including a characteristic staining profile for C4d.     

我国大陆恶性高热病例的分析

目的 分析我国大陆恶性高热（MH）病例的临床资料，探讨诊断和治疗中应注意的问题。方法 检索中国生物医学文献数据库，收集1978年1月至2004年3月报道的MH病例34例，分析其流行病学特征、发病特点、临床表现、治疗及转归。结果 我国大陆报道的MH病例以青少年居多，男性多于女性，集中在口腔科手术（尤其是唇腭裂修补术）、骨科手术和小儿外科手术（尤其是先天畸形矫治术），典型的临床表现为突然发生的高碳酸血症、体温急剧升高和骨骼肌僵直等。诊断上主要是根据临床表现，尚未建立骨骼肌体外收缩试验方法，治疗上主要是对症处理，缺乏特效药物（丹曲林）。结论 近几年我国大陆MH病例逐渐增加，应加强对MH发病机制的研究，尽快建立MH的实验诊断标准，增强预防、诊断和治疗MH的能力。     

Modulation of ryanodine-induced contractures in human skeletal muscle pretreated with dantrolene

Dantrolene seems to be the causal therapy in malignant hyperthermia (MH) crisis but the complex mechanisms of MH and dantrolene therapy are still not fully understood. The influence of dantrolene on ryanodine-induced contractures has been reported in animal studies only. In the present study 20 patients from] 7 families were tested for MH using the protocol of the European Malignant Hyperthermia Group. In addition ryanodine-induced contractures were evaluated following bolus application of 10.0 μmol · 1^-1 ryanodine. After pretreatment with 1 μimol · 1^-1 dantrolene ryanodine-provoked contractures developed significantly later in MHS (15.8±1.8 min) and MHN (46.0±4.2 min) muscle specimens than after ryanodine alone (MHS 4.8±0.7 min), (MHN 13.7±0.9 min). They were no longer observed in either group after pretreatment with 5 μimol · 1^-1 dantrolene. We conclude that dantrolene is able to attenuate ryanodine-induced contractures dose-dependendy, and therefore it is speculated that dantrolene could specifically act at the ryanodine receptor binding site.     

普拉固和鱼油对高胆固醇血症患者血脂与心脑血管事件影响的比较

目的:比较普拉固和鱼油对高胆固醇血症患者的血脂、血粘度、血管内皮功能和心脑血管事件的影响。方法:对266例原发性高胆固醇血症患者经2周洗脱期后,随机分为两组,普拉固组,初服10mg,每晚一次,8周后若TC仍>5.2mmol/L,LDL—ch>3.12mmol/L,则加量至20mg/d,每8周再查血脂,以达到TC<5.2mmol/L,LDL—ch<3.12mmol/L的量作治疗量继续服用。鱼油组,服美国深海鱼油一日三次,一次3g,均于服药8周复查血脂、血粘度及血管内皮功能等并作16月随访。结果:治疗8周,TC,普拉固组下降26％,鱼油组下降12％(P<0.01)。LDL—ch,普拉固组下降31％,鱼油组下降11％(P<0.01),肱动脉流量介导的舒张与硝酸甘油介导的舒张,普拉固组分别增加104％和19％,鱼油组无明显改变。全血低切粘度,普拉固组减少23％,鱼油组减少10％(P<0.01)。平均随访16月,普拉固组中脑出血1例(0.8％),鱼油组发生心脑血管事件7例(5.3％),死亡1例(P<0.05)。两组均无明显的不良反应。结论:普拉固是一个安全有效的降脂药,能改善血管内皮功能,降低血粘度,减少高胆固醇血症病人心脑血管事件发生。     

高温、亚低温对大鼠脑缺血再灌注损伤的作用及其机制研究

目的：研究轻度高温、亚低温对大鼠脑缺血再灌注损伤组织兴奋性氨基酸（EAA）与氧自由基的相互关系及病理损伤程度的影响。方法：60只Wistar大鼠按不同脑温条件随机分为生化组（n=28）和病理组（n=32)，采用改良Nagasawa局灶脑缺血再灌注模型，观察脑缺血再灌注损伤组织谷氨酸（Glu），超氧化物歧化酶（SOD）、丙二醛（MDA）的变化及光镜，电镜下的病理变化。结果：轻度高温明显加重常温脑缺血再灌注损伤组织Glu、MDA的升高（P＜0．01）及SOD的下降（P＜0．05），加重常温脑缺血再灌注组织病理损伤程度，亚低温的作用则相反，结论：轻度高温可能通过同时促进EAA合成，释放和氧自由基生成系统活化，造成大鼠脑缺血再灌注损组织损伤加重；亚低温可能通过同时抑制EAA合成，释放和氧自由基生成系统活化，减轻大鼠脑缺血再灌注组织损伤程度，对大鼠脑缺血再灌注损伤组织起保护作用。     

A case of nocturnal fainting: supine vasovagal syncope.

Supine loss of consciousness is a relatively rare occurrence prompting investigations for underlying causes as diverse as cardiac arrhythmia, hypoglycaemia and nocturnal epilepsy. Neurally mediated syncope is rarely implicated as the cause of symptoms in supine loss of consciousness because of the absence of orthostatic stress and gravitational relative preservation of cerebral perfusion, but we report here on a case of recurrent, atypical and troublesome vasovagal syncope occurring at night while supine. Diagnosis aided by head-up tilt table testing and conservative management brought about complete resolution of symptoms.     

鼻内镜下或间接喉镜下微波热凝术治疗声带息肉声带小结

目的探讨间接喉镜下或鼻内镜下微波热凝治疗声带息肉或小结的效果。方法对321例在间接喉镜或鼻内镜下微波热凝治疗声带息肉或小结病例资料进行分析。结果321例患者均一次手术成功。术后随诊3个月～一年以上的321例患者,治愈率92%,好转率8%。无效率为0。术中和术后未发生并发症。结论间接喉镜下或鼻内镜下微波热凝治疗声带息肉声带小结,具有操作安全、方便、不出血、快捷、简单、治愈率高等优点。     

三维适形放疗联合肝动脉碘油栓塞化疗并热疗治疗原发性肝癌的疗效研究

目的:探讨原发性肝癌的肝动脉碘油栓塞化疗(TACE)、热疗、三维适形放疗(3DCRT)的综合治疗价值。方法:122例原发性肝癌患者进行前瞻性随机分组研究,综合治疗组64例,行TACE并3DCRT,结合热疗治疗。对照组58例3DCRT治疗,联合TACE。结果:1、2、3年生存率综合治疗组分别为85%、65%、39%,对照组分别为59%、30%、18%(P<0.05)两组毒副作用相似。结论:对于非手术切除的原发性肝癌患者,TA-CE,结合3DCRT并热疗,能明显提高疗效,而毒副作用不增加。