人用轮状病毒疫苗研究进展

轮状病毒（rotavirus，RV）是全球范围内导致婴幼儿腹泻的主要病原体之一。研究表明干净的水源和良好的卫生环境不能阻断RV传播，且目前尚无特异性治疗RV性腹泻的药物，使用RV疫苗是唯一有效的防控手段。此文对RV疫苗的使用现状、研发进展及面临的挑战做一综述。     

Rotaviruses: Is their surveillance needed?

Rotaviruses, a major cause of gastroenteritis in children worldwide accounts for around 0.5 million deaths annually. Owing to their segmented genome and frequently evolving capability, these display a wide variation in their genotypes. In addition to commonly circulating genotypes (G1, G2, G3, G4, G9, P[4] and P[8]), a number of infrequent genotypes are being continuously reported to infect humans. These viral strains exhibit variation from one geographical setting to another in their distribution. Though the introduction of vaccines (RotaTeq and Rotarix) proved to be very effective in declining rotavirus associated morbidity and mortality, the number of infections remained same. Unusual genotypes significantly contribute to the rotavirus associated diarrhoeal burden, may reduce the efficacy of the vaccines in use and hence vaccinated individuals may not be benefited. Vaccine introduction may bring about a notable impact on the distribution and prevalence of these viruses due to selection pressure. Moreover, there is a sudden emergence of G2 and G3 in Brazil and United States, respectively, during the years 2006–2008 post-vaccination introduction; G9 and G12 became predominant during the years 1986 through 1998 before the vaccine introduction and now are commonly prevalent strains; and disparity in the predominance of strains after introduction of vaccines and their natural fluctuations poses a vital question on the impact of vaccines on rotavirus strain circulation. This interplay between vaccines and rotavirus strains is yet to be explored, but it certainly enforces the need to continuously monitor these changes in strains prevalence in a particular region. Furthermore, these fluctuations should be considered while administration or development of a vaccine, if rotavirus associated mortality is ever to be controlled.     

Enhancing viral vaccine production using engineered knockout vero cell lines – A second look

The global adoption of vaccines to combat disease is hampered by the high cost of vaccine manufacturing. The work described herein follows two previous publications (van der Sanden et al., 2016; Wu et al., 2017) that report a strategy to enhance poliovirus and rotavirus vaccine production through genetic modification of the Vero cell lines used in large-scale vaccine manufacturing. CRISPR/Cas9 gene editing tools were used to knockout Vero target genes previously shown to play a role in polio- and rotavirus production. Subsequently, small-scale models of current industry manufacturing systems were developed and adopted to assess the increases in polio- and rotavirus output by multiple stable knockout cell lines. Unlike previous studies, the Vero knockout cell lines failed to achieve desired target yield increases. These findings suggest that additional research will be required before implementing the genetically engineered Vero cell lines in the manufacturing process for polio- and rotavirus vaccines to be able to supply vaccines at reduced prices.     

中药联合阿奇霉素治疗急性肠炎48例

目的：观察中药联合阿奇霉素治疗急性肠炎的临床疗效。方法：将96例急性肠炎患者随机分为对照组、治疗组各48例。2组均给予止吐、解痉、纠正水电解质平衡等对症治疗，并嘱患者注意饮食。对照组同时给予阿奇霉素注射液0.5 g+250 mL0.9%氯化钠注射液静脉滴注，1次/d，3天为1个疗程。观察组在对照组治疗的基础上给予自拟中药，1剂/d，早晚各服1次。2组均以治疗3天为1个疗程。结果：总有效率观察组为97.92%，对照组为87.50%。2组相比差异显著（P＜0.05）。观察组症状、体征改善及消失时间均短于对照组，2组比较差异显著（P＜0.05）。结论：中药联合阿奇霉素治疗急性肠炎临床疗效显著，可缩短病程。     

Overview of stem cell therapy for Crohn's disease

Background: Crohn's disease (CD) therapy is rapidly evolving. Recent and ongoing clinical trials using immunologically active stem cells (SC) for the treatment of CD demonstrate the potential for this novel therapy to induce complete and long-lasting remission of symptoms in settings where ‘standard’ therapies have been unsuccessful. Objective/methods: This review of SC, including mesenchymal stem cell (MSC) therapy for CD discusses how the immunological effects of MSC may correct some of the pathophysiological defects underpinning CD, and examines the latest clinical trial data providing evidence of their efficacy in the treatment of Crohn's disease. Results/conclusions: Given the beneficial effects on mucosal healing seen in animal models of inflammation and results from early clinical trials, MSC may serve as a candidate therapy for patients who have failed to respond to biological therapy.     

热毒宁注射液治疗50例小儿病毒性肠炎的临床疗效观察

目的探讨热毒宁注射液治疗小儿病毒性肠炎的临床疗效与安全性。方法将100例患儿随机分为观察组和对照组各50例,对照组静脉点滴病毒唑,观察组静脉点滴热毒宁注射液,均治疗3 d;比较2组治疗后的临床疗效、止泻时间、退热时间、治愈时间的差异。结果观察组总有效率、止泻时间、退热时间、治愈时间均明显优于对照组,差异有统计学意义(P<0.01)。结论热毒宁治疗病毒性肠炎患儿能有效改善发热、腹泻的症状,提高治疗效果,缩短治疗疗程,值得临床推广使用。     

血清SIL-2R、IL-8和TNF水平在轮状病毒（RV）肠炎发病中的作用机制研究

目的：了解血清SIL-2R、IL-8和TNF水平在轮状病毒(RV)肠炎发病中的作用机制。方法随机择取该院2012年3月-2014年3月收治的50例RV肠炎患儿为实验组,并选择同期来该院体查的50例健康体检者为对照组,应用双抗体夹心ELISA法,对两组血清中SIL-2R、IL-8及TNF-A水平进行检测,观察两组各个指标变化情况。结果实验组RV肠炎患儿在急性期血清中SIL-2R、TNF-A、IL-8水平(45.23±11.23)pg/mL,(122.23±6.75)pg/mL,(526.43±12.54)pg/mL明显高于正常对照组(28.64±9.62)pg/mL,(68.12±5.46)pg/mL,(197.32±14.24) pg/mL,差异有统计学意义(P<0.05)。与对照组比较,轻症组、中症组、重症组RV肠炎患儿血清IL-8、SIL-2R及TNF-A水平亦呈增高趋势,差异有统计学意义(P<0.05),提示三者与病情轻重具有关联性。结论血清IL-8、SIL-2R、TNF-A在轮状病毒感染免疫防御与免疫损伤机制中具有重要的引导作用,临床上应引起足够重视。     

Catching-up with pentavalent vaccine: Exploring reasons behind lower rotavirus vaccine coverage in El Salvador

Rotavirus vaccine was introduced in El Salvador in 2006 and is recommended to be given concomitantly with DTP–HepB–Haemophilus influenzae type b (pentavalent) vaccine at ages 2 months (upper age limit 15 weeks) and 4 months (upper age limit 8 months) of age. However, rotavirus vaccination coverage continues to lag behind that of pentavalent vaccine, even in years when national rotavirus vaccine stock-outs have not occurred. We analyzed factors associated with receipt of oral rotavirus vaccine among children who received at least 2 doses of pentavalent vaccine in a stratified cluster survey of children aged 24–59 months conducted in El Salvador in 2011. Vaccine doses included were documented on vaccination cards (94.4%) or in health facility records (5.6%). Logistic regression and survival analysis were used to assess factors associated with vaccination status and age at vaccination. Receipt of pentavalent vaccine by age 15 weeks was associated with rotavirus vaccination (OR: 5.1; 95% CI 2.7, 9.4), and receipt of the second pentavalent dose by age 32 weeks was associated with receipt of two rotavirus vaccine doses (OR: 5.0; 95% CI 2.1–12.3). Timely coverage with the first pentavalent vaccine dose was 88.2% in the 2007 cohort and 91.1% in the 2008 cohort (p = 0.04). Children born in 2009, when a four-month national rotavirus vaccine stock-out occurred, had an older median age of receipt of rotavirus vaccine and were less likely to receive rotavirus on the same date as the same dose of pentavalent vaccine than children born in 2007 and 2008. Upper age limit recommendations for rotavirus vaccine administration contributed to suboptimal vaccination coverage. Survey data suggest that late rotavirus vaccination and co-administration with later doses of pentavalent vaccine among children born in 2009 helped increase rotavirus vaccine coverage following shortages.