Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection

Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4⁺ and CD8⁺ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity.     

pre-miR-27a单核苷酸多态与非吸烟女性肺癌发生的相关性

目的:探讨miR-27a(rs895819，A>G)多态与非吸烟女性肺癌发生的相关性。方法:采用病例-对照研究方法，使用PCR-RFLP技术检测90例非吸烟女性原发性肺癌患者和97例非吸烟女性体检者rs895819位点基因型分布频率。非条件Logistic统计分析不同基因型与肺癌发生的相关性，并分析该多态与烹饪油烟暴露的协同效应及与临床参数的相关性。结果:肺癌组rs895819 位点GG突变基因型和G等位基因频率明显高于对照组(P=0.047,P=0.016)。AG+GG基因型明显增加了非吸烟女性肺癌的发生风险(OR=1.82，95%CI=1.01～3.28，P=0.038)。肺癌组和对照组烹饪油烟暴露率分别为57%和42%，差异有统计学意义(P=0.035)。回归分析显示该多态位点与烹饪油烟无交互作用；与临床病理特征(病理类型，临床分期和淋巴结转移)均无相关性。结论:has-miR-27a rs895819 G等位基因增加了非吸烟女性肺癌发生的风险。     

温针灸阳陵泉穴治疗膝关节骨性关节炎临床疗效观察

目的:观察温针灸阳陵泉穴治疗膝关节骨性关节炎的临床疗效。方法:将2015年1月至2019年1月本院收治的膝关节骨性关节炎患者120例,根据随机数字表法分为对照组和观察组,每组60例。对照组给予等速肌力训练治疗,观察组在对照组的基础上加用温针灸阳陵泉穴治疗。观察两组患者膝关节屈曲度、伸直度,白细胞介素(interleukin,IL)-6及IL-18水平,VAS评分及膝关节症状和功能评分。结果:观察组治疗后屈曲度及伸直度均高于对照组,差异有统计学意义(P<0.05);观察组治疗后IL-6及IL-18水平均低于对照组,差异有统计学意义(P<0.05);观察组治疗后VAS评分低于对照组,差异有统计学意义(P<0.05);观察组治疗后症状和功能评分高于对照组,差异有统计学意义(P<0.05);观察组有效率95.0%,对照组有效率83.3%,观察组有效率高于对照组,差异有统计学意义(P<0.05)。结论:温针灸阳陵泉穴治疗膝关节骨性关节炎,可有效改善患者膝关节活动度,降低炎症因子,减轻疼痛,提高临床疗效。     

miR-29a靶向调控CLDN1抑制肝癌细胞增殖的实验研究

目的:探讨miR-29a在肝癌组织中的表达水平，及其对人肝癌细胞增殖能力的影响。方法:通过RT-PCR测定肝癌组织及非肝癌组织中miR-29a的表达水平；将携带miR-29a的脂质体miR-29a mimic、空载体miR-NC以及miR-29a抑制剂anti-miR-29a转染入肝癌细胞系HepG2和HLE，通过RT-PCR方法检测miR-29a对肝癌细胞系HepG2、HLE增殖能力影响；通过Targetscan软件预测miR-29a靶基因，采用Western blot及荧光素酶实验验证。结果:与非肝癌组织比较，miR-29a在肝癌组织中表达下调，MTT实验提示:miR-29a高表达组肝癌细胞增殖能力较弱，miR-29a低表达组肝癌细胞增殖能力提高。Targetscan软件提示:CLDN1可能为miR-29a靶基因，Western blot及荧光素酶实验提示:与阴性对照组相比，miR-29a高表达组内CLDN1表达下降，相反miR-29a低表达组内CLDN1表达增加。结论:miR-29a在肝癌细胞及组织中表达下调，并且可能通过调控CLDN1影响肝癌细胞增殖能力。     

肺癌miR-146a表达及其对细胞增殖、侵袭及迁移的影响

目的探讨微小RNA-146a(miR-146a)在肺癌组织和细胞中的表达和甲基化状态,及其对A549细胞增殖、侵袭、迁移的影响及可能机制。方法收集2018年1月至2019年4月在我院行根治性手术的非小细胞肺癌组织和对应癌旁组织,实时荧光定量PCR(QPCR)和甲基化特异性PCR(MSP)检测miR-146a的表达水平和甲基化状态,并分析甲基化状态与肺癌临床病理特征的关系。采用5-氮杂-2’-脱氧胞苷(5-AZA-2’-dC)处理A549细胞(处理组),MTT、Transwell实验和划痕实验检测处理组细胞增殖、侵袭和迁移活性。采用Western blotting检测Notch1和发状分裂相关增强子1(Hes-1)蛋白表达。结果肺癌组织和A549细胞中miR-146a表达量分别为0.63±0.28、0.85±0.11,均低于癌旁正常组织和BEAS-2B细胞(P<0.05)。MSP检测显示肺癌组织miR-146a甲基化率为62.5%(50/80),高于癌旁组织(P<0.05);miR-146a甲基化状态与肿瘤直径、TNM分期、淋巴结转移有关(P<0.05)。处理组细胞miR-146a表达水平为2.15±0.48,高于空白对照组(P<0.05);处理组细胞增殖、侵袭和迁移活性均低于空白对照组(P<0.05)。处理组Notch1蛋白和Hes-1蛋白表达水平分别为0.24±0.05和0.22±0.06,均低于空白对照组(P<0.05)。结论启动子异常甲基化导致在肺癌组织和细胞中miR-146a表达量降低,可能通过减弱对Notch1/Hes-1信号通路的抑制作用,促进肺癌细胞增殖、侵袭和转移,miR-146a有望成为肺癌新的生物治疗靶点。     

miR-892a regulated PPP2R2A expression and promoted cell proliferation of human colorectal cancer cells

Colorectal cancer (CRC) is one of the most common malignancy cancers in the world. Aberrant microRNA expression is involved in human diseases including cancer. In the present study, we investigated the miR-892a's role in CRC cell proliferation. We found that miR-892a was frequently upregulated in human colorectal cancer tissues and cell lines compared with the matched tumor adjacent tissues and normal colonic cell line FHC. Overexpression of miR-892a promoted cell proliferation and colony formation of CRC. Bioinformatics analysis further revealed PPP2R2A was identified as a potential miR-892a. Overexpression of miR-892a-in SW480 cells reduced PPP2R2A protein expression. Subsequently, data from luciferase reporter assays showed that PPP2R2A 3′-untranslated region (3′-UTR) carried the directly binding site of miR-892a. Furthermore, siRNA-mediated silencing of PPP2R2A blocked the inhibitory effect of miR-892a-in on CRC cell growth. In sum, our data provided compelling evidence that overexpression of miR-892a may provide a selective growth promotion for CRC cells by direct suppression of PPP2R2A expression.     

Deconstructing myths,building alliances: a networking model to enhance tobacco control in hospital mental health settings

Life expectancy for people with severe mental disorders is up to 25 years less in comparison to the general population, mainly due to diseases caused or worsened by smoking. However, smoking is usually a neglected issue in mental healthcare settings. The aim of this article is to describe a strategy to improve tobacco control in the hospital mental healthcare services of Catalonia (Spain). To bridge this gap, the Catalan Network of Smoke-free Hospitals launched a nationwide bottom-up strategy in Catalonia in 2007. The strategy relied on the creation of a working group of key professionals from various hospitals —the early adopters— based on Rogers’ theory of the Diffusion of Innovations. In 2016, the working group is composed of professionals from 17 hospitals (70.8% of all hospitals in the region with mental health inpatient units). Since 2007, tobacco control has improved in different areas such as increasing mental health professionals’ awareness of smoking, training professionals on smoking cessation interventions and achieving good compliance with the national smoking ban. The working group has produced and disseminated various materials, including clinical practice and best practice guidelines, implemented smoking cessation programmes and organised seminars and training sessions on smoking cessation measures in patients with mental illnesses. The next challenge is to ensure effective follow-up for smoking cessation after discharge. While some areas of tobacco control within these services still require significant improvement, the aforementioned initiative promotes successful tobacco control in these settings.     

Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Evolución e impacto bibliométrico de las becas de la Sociedad Española de Cardiología/Fundación Española del Corazón en el periodo 2007-2012

Introduction and objectivesThe Spanish Society of Cardiology/Spanish Heart Foundation (SEC/FEC) annually awards grants for cardiovascular research projects. Our objective was to analyze the trend in these investments and their resulting scientific production from 2007 to 2012.MethodsA search of the publications funded by the SEC/FEC was carried out, according to the following inclusion criteria: publication in a journal indexed in MEDLINE or EMBASE, publication date after the grant, authorship by the principal investigator of the grant, and acknowledgment of SEC/FEC funding. The impact factor and subsequent citations of the articles were analyzed (Web of Science).ResultsA total of 235 grants were awarded (39/y) with an allocation of €3 854 300 (€642 383/y), 37% of them to women. In all, 122 publications resulted from 88 research projects (37%) funded by the SEC/FEC. Up to October 2017, these publications had received 2258 citations in subsequent studies in the Web of Science, with a mean of 18.5 and a median of 8 citations/study.ConclusionsDespite the economic crisis, the mean number and size of the grants awarded by the SEC/FEC increased in the period analyzed. Grants were awarded on an equal opportunity basis to men and women. The bibliometric impact of the funded projects is acceptable, although efforts should be made to improve it.