Immunogenicity and safety of an E. coli-produced bivalent human papillomavirus (type 16 and 18) vaccine: A randomized controlled phase 2 clinical trial

BackgroundThis study aimed to investigate the dosage, immunogenicity and safety profile of a novel human papillomavirus (HPV) types 16 and 18 bivalent vaccine produced by E. coli.MethodsThis randomized, double-blinded, controlled phase 2 trial enrolled women aged 18–25 years in China. Totally 1600 eligible participants were randomized to receive 90 μg, 60 μg, or 30 μg of the recombinant HPV 16/18 bivalent vaccine or the control hepatitis B vaccine on a 0, 1 and 6 month schedule. The designated doses are the combined micrograms of HPV16 and 18 VLPs with dose ratio of 2:1. The immunogenicity of the vaccines was assessed by measuring anti-HPV 16 and 18 neutralizing antibodies and total IgG antibodies. Safety of the vaccine was assessed.ResultsAll but one of the seronegative participants who received 3 doses of the HPV vaccines seroconverted at month 7 for anti-HPV 16/18 neutralizing antibodies and IgG antibodies. For HPV 16, the geometric mean titers (GMTs) of the neutralizing antibodies were similar between the 60 μg (GMT = 10,548) and 90 μg (GMT = 12,505) HPV vaccine groups and were significantly higher than those in the 30 μg (GMT = 7596) group. For HPV 18, the GMTs of the neutralizing antibodies were similar among the 3 groups. The HPV vaccine was well tolerated. No vaccine-associated serious adverse events were identified.ConclusionThe prokaryotic-expressed HPV vaccine is safe and immunogenic in women aged 18–25 years. The 60 μg dosage formulation was selected for further investigation for efficacy.Clinical trials registration: NCT01356823.     

A model of health care provider decision making about HPV vaccination in adolescent males

IntroductionIn the U.S., HPV vaccination of adolescent males remains low, despite the recommendation for routine vaccination. Although research has highlighted that health care provider (HCP) recommendation is very influential in HPV vaccine uptake, research on this topic in the male population is lacking. Accordingly, we used a qualitative approach to identify HCP knowledge, attitudes, and behaviors regarding adolescent male HPV vaccination, one year, after routine vaccination of adolescent males was recommended.MethodA total of 20 U.S. pediatric HCPs participated in 20–30 min interviews about knowledge, attitudes, and practices regarding male HPV vaccination. Interviews were audio-recorded, transcribed and, analyzed using inductive content analysis.ResultsThe providers had been in practice for 1–35 years, 75% were female, and 75% were White. Opinions on HPV vaccination were shaped by knowledge/perception of the risks and benefits of vaccination. Although all providers frequently offered HPV vaccine to male patients, the strength and content of the offer varied greatly. Vaccination opinions determined what issues were emphasized in the vaccine offer (e.g., stressing herd immunity, discussing prevention of genital warts), while adolescent age influenced if and how they pitched their vaccine offer (e.g., HPV as a STI). Most providers agreed with the ACIP recommendations, however, several expressed that providers’ preexisting opinions might remain unchanged despite the recommendations. Consistent with the literature on determinants of HPV vaccination, providers believed that their own recommendation was a major factor in a family's decision to vaccinate. Barriers to vaccination included the “newness” and sexual nature of the vaccine, lack of insurance coverage, and the vaccine not being mandated.ConclusionsProviders’ opinions about, and approaches to offering, HPV vaccination to males were highly variable. Interventions designed to improve male HPV vaccination should focus on helping providers to routinely recommend the vaccine to all of their eligible patients, both males and females.     

Immunogenicity and safety of the new intradermal influenza vaccine in adults and elderly: A randomized phase 1/2 clinical trial

BackgroundRecent clinical evidence indicates that an intradermal (ID) delivery of vaccines confers superior immunogenicity as compared to a standard intramusclular or subcutaneous (SC) delivery.MethodsIn this exploratory study, 600 healthy adults were randomized to 6 study groups with subgroups of young adults (20–64 years old) and older adults (65 years and older). The subjects were either injected by a novel ID injection system with a single dose of 6, 9, or 15 μg HA or two doses (21 days apart) of 15 μg HA per strain or injected by an SC injection method with a single or two doses (21 days apart) of 15 μg HA per strain. Immunogenicity was assessed using hemagglutination inhibition (HAI) titer and microneutralization titer on Days 0, 10, 21, and 42. Solicited and unsolicited adverse events were recorded for 7 and 21 days post-vaccination, respectively.ResultsIn both young adults and older adults groups, the geometric titer (GMT) ratios of HAI in the ID 15 μg HA group were higher than those in the SC 15 μg HA group on both Day 10 and Day 21, while those in the ID 6 and ID 9 μg HA groups were comparable with those in the SC 15 μg HA group. The kinetics of GMTs of HAI suggested that the ID vaccine has the potential to induce the prompt immune response, which is rather hampered in older adults as seen in the SC vaccine groups. The injection-site AEs were generally mild and transient, and did not occur in a dose or dosage-dependent manner.ConclusionsThe results of this study clearly suggest that the immunologic profile of the ID vaccine is better than that of the SC vaccine, while the safety profile of the ID vaccine is similar to that of the SC vaccine. In this exploratory study with almost 100 subjects per each group, single or two-dose administration of the ID vaccine containing 15 μg HA was suggested to be an appropriate regimen in order to prevent influenza and to reduce the associated disease burden.Trial registrationJAPIC Clinical Trials Information (JapicCTI-132096).     

建立“全院共享、流程自动”的人力资源信息系统

信息化是医院人力资源管理发展的一种趋势。本文以某县级医院人力资源管理信息化实践为基础,提出借助商品化软件、内外网结合、全院共享的信息化思路,通过细致筛选软件产品、医院主导软件实施、运行中持续改进等具体做法,实现实施技术向医院的成功转移,捋顺薪酬管理流程,建立全院共享的人力资源信息系统。人事信息系统的建立提高人事信息的利用效率,为医院的管理决策提供有效支撑。本文总结建设思路和做法,为其他县级医院人力资源信息化建设提供借鉴。     

The Return of Actionable Variants Empirical (RAVE) Study,a Mayo Clinic Genomic Medicine Implementation Study: Design and Initial Results

Objectives

To identify clinically actionable genetic variants from targeted sequencing of 68 disease-related genes, estimate their penetrance, and assess the impact of disclosing results to participants and providers.

高糖条件下人视网膜色素上皮细胞的上皮-间质转化

背景 研究证实,有多种细胞参与增生性玻璃体视网膜病变(PVR)的发生和发展过程,其中RPE细胞的上皮-间质转化(EMT)可能与PVR有关,其主要生物学行为是RPE细胞的增生和迁移.已证实高血糖是糖尿病视网膜病变(DR)发病的主要原因,而高糖条件下RPE细胞是否发生EMT鲜有报道. 目的 建立体外高糖细胞培养模型,探讨高糖对人RPE的迁移能力及EMT的影响.方法 用含质量分数10％胎牛血清的DMEM/F12培养基对人RPE细胞D407细胞株进行体外培养和传代,取6～8代细胞用于实验.依据培养液中血糖浓度的不同将细胞分为3个组,正常对照组培养基中葡萄糖终浓度为5.5 mmol/L,高糖培养组葡萄糖终浓度为60.0 mmol/L,用含5.5 mmol/L葡萄糖和甘露醇的DMEM培养基培养细胞作为高渗对照组.采用细胞划痕试验法检测划痕后0、24、48和72 h时3个组RPE细胞的迁移率,用实时荧光定量PCR(real-time PCR)检测高糖培养组在培养不同时间点RPE细胞间质化标志物闭锁小带蛋白-1(ZO-1)和α-平滑肌肌动蛋白(α-SMA)mRNA在细胞中的相对表达水平.结果 正常对照组培养的RPE细胞呈多角形,核仁清晰,排列致密;高糖培养组随着培养时间的延长,RPE细胞逐渐变大、变长,细胞结构不清,排列紊乱;高渗对照组细胞结构接近正常对照组.划痕试验显示,高糖培养组在划痕后48 h可见细胞迁移,划痕后72 h划痕基本消失,而正常对照组和高渗对照组划痕仍然存在.划痕后各时间点高糖培养组细胞迁移率明显高于正常对照组和高渗对照组,组间和各时间点的差异均有统计学意义(F分组=328.600,P=0.000;F时间=773.270,P=0.000).RT-PCR结果显示,与正常对照组相比,高糖培养后48 h、72 h组细胞中ZO-1 mRNA的表达水平明显低于正常对照组,而α-SMA mRNA的表达水平明显高于正常对照组,差异均有统计学意义(均P＜0.05).结论 高糖条件下RPE细胞的迁移能力增强,发生EMT改变,可能参与增生性糖尿病视网膜病变(PDR)的发生.     

计算机辅助设计与制作技术在眼眶爆裂性骨折治疗中的应用及疗效评价

背景 眼眶爆裂性骨折引起明显的眼球形态和功能的异常.眼眶解剖结构复杂,故眼眶骨折修复手术中植入物的设计和制作具有一定的难度,而计算机辅助设计与制作(CADM)技术有望提供一种新的方法,但其临床应用价值有待评估.目的 研究CADM技术在眼眶爆裂性骨折治疗中的应用方法,评价其临床效果.方法 对河南省眼科研究所河南省立眼科医院2006年7月至2012年7月收治的眼眶爆裂性骨折患者74例74眼的手术过程和疗效进行回顾性分析,其中CADM手术者58例58眼,非CADM手术者16例16眼,2个组间患者基线特征,如年龄、性别和眼别均匹配.CADM手术组术眼采用CADM技术进行个体化三维立体植入物的设计和制作并进行眶骨骨折缺损处的填充,非CADM手术组术眼采用常规羟基磷灰石人工骨或多孔聚乙烯高分子合成材料(Medpor)填充法.所有术眼术前均行常规眼部检查以及CT检查,术后随访22～69个月,在随访期间内定期进行眼部临床观察和CT检查.观察指标包括最佳矫正视力、眼球突出度、眼球位置、眼球运动和复视改善情况以及并发症情况.结果 CADM手术组和非CADM手术组术眼术前最佳矫正视力分别为0.71±0.37和0.69±0.41,术后最佳矫正视力分别为0.74±0.38和0.72±0.41,组间差异无统计学意义(F分组=0.043,P=0.837),术眼手术前后视力的总体比较差异有统计学意义(F时间=13.576,P＜0.01),其中2个组术眼术后视力均好于术前,差异均有统计学意义(均P＜0.05).2个组间复视和眼球运动障碍治愈和好转的眼数分布差异均无统计学意义(Z=-0.298,P=0.766;Z=-0.548,P=0.584).CADM手术组和非CADM手术组术眼术前眼球眼球内陷度值分别为(3.93±0.99) mm和(3.88±0.97)mm,术后分别为(0.91±0.67)mm和(1.84±0.80)mm,组间总体比较差异无统计学意义(F分组=3.558,P=0.063),各组术眼术后眼球眼球内陷度值均明显低于术前,差异均有统计学意义(均P＜0.05).CT影像显示,CADM手术组术眼植入物在位,与眶骨骨折缺损处贴合良好,患者眼球位置及外观均恢复正常.非CADM手术组术眼发生植入物翘起并损伤内直肌.随访期内CADM手术组未发现组织感染、排斥反应等不良反应.结论 CADM技术用于眼眶爆裂性骨折的治疗可重建三维立体骨性眼眶,并有效改善患眼位置、眼球运动功能和视觉功能,其疗效优于传统植入物填充术.     

重组质粒pRNAT-U6.1/CFB siRNA的构建、鉴定及其对人脐静脉内皮细胞增生的影响

背景 脉络膜新生血管(CNV)是多种眼部疾病致盲的原因之一,研究发现补体系统在CNV的发病机制中起重要作用.目的 构建针对补体因子B(CFB)的小干扰RNA(siRNA)重组质粒,体外观察其对人脐静脉内皮细胞ECV-304增生的影响.方法 根据人CFB的基因序列设计引物,经PCR扩增后与质粒pRNAT-U6.1连接,得到重组质粒pRNAT-U6.1/CFB siRNA,并进行测序鉴定和PCR鉴定.ECV-304细胞株进行常规培养,用电转染技术将重组质粒或空质粒分别转染人ECV-304细胞株,分为CFB-siRNA转染组和空质粒转染组,未转染的细胞为空白对照组.细胞转染后继续培养48 h,于倒置荧光显微镜下观察绿色荧光蛋白(GFP)的表达并计算转染效率;采用半定量逆转录PCR(RT-PCR)法测定各组细胞中CFB mRNA的相对表达量;用MTT法检测各组细胞转染24、48和72 h时细胞的增生值(A)并计算生长抑制率;利用流式细胞技术检测各组细胞的生长周期变化.结果 PCR扩增的目的片段序列与CFB基因序列完全相符,ECV-304细胞转染后,倒置荧光显微镜下可见CFB-siRNA转染组和空质粒转染组的细胞中GFP呈绿色荧光.半定量RT-PCR结果显示,CFB-siRNA转染组、空质粒转染组和空白对照组的CFB mRNA相对表达量分别为0.07±0.04、0.14±0.02和0.14 ±0.03,总体比较差异有统计学意义(F=233.05,P=0.00);其中CFB-siRNA转染组CFB mRNA相对表达量明显低于空质粒转染组和空白对照组,差异均有统计学意义(均P＜0.05).MTT法检测结果显示,各组不同时间细胞增生抑制率总体比较差异有统计学意义(F分组=212.99,P=0.00);CFB-siRNA转染组细胞转染24、48、72 h后细胞增生的抑制率分别为(23.45±0.01)％、(33.48±0.02)％和(45.49±0.01)％,明显高于同时间点空质粒转染组和空白对照组,差异均有统计学意义(均P＜0.05).流式细胞仪检测结果显示,CFB-siRNA转染组、空质粒转染组和空白对照组G1期的细胞数占总细胞数的(44.4±0.5)％、(25.8±0.4)％和(27.9±0.6)％,总体比较差异有统计学意义(F=58.98,P=0.00);CFB-siRNA转染组G1期和G2期细胞所占百分比显著高于空白对照组和空质粒转染组,差异均有统计学意义(均P＜0.05).结论 重组质粒pRNAT-U6.1/CFB siRNA可通过将细胞阻滞在G1期而有效抑制人脐静脉内皮细胞的增生.