延续护理干预对慢性乙型肝炎患者抗病毒治疗依从性的影响观察

目的:分析延续护理干预对慢性乙型肝炎患者抗病毒治疗依从性的影响。方法:研究选取2017年1月~2017年12月某院肝二病区收治的112例乙型肝炎患者和2018年1月~2018年12月收治的98例乙型肝炎病毒患者作为研究对象,所有患者均进行抗病毒治疗,回顾性分析患者的病历资料。将2017年收治的112例患者作为常规组实施常规护理,将2018年收治的98例患者的作为研究组实施延续性护理,比较两组的护理效果。结果:研究组的治疗依从率为93.88%(92例),远高于常规组的77.68%(87例),两组数据比较存在统计学意义(P<0.05)。结论:延续性护理措施可以有效提高慢性乙型肝炎抗病毒治疗的依从性,可以在临床中推广使用。     

负载IL-4及BMP-2的氧化石墨烯-羧甲基壳聚糖凝胶对骨免疫和骨修复的早期影响研究

目的探讨负载 IL-4 和 BMP-2 的氧化石墨烯（graphene oxide，GO）-羧甲基壳聚糖（carboxymethyl chitosan，CMC）凝胶诱导巨噬细胞 M2 型分化及对 BMSCs 成骨分化的影响。方法取 CMC、GO 制备混合溶液后，分别添加 PBS、IL-4、BMP-2 或 IL-4+BMP-2，在交联剂作用下制备单纯或负载不同因子的 GO-CMC 凝胶支架；取单纯 GO-CMC 凝胶表征观测，包括大体、扫描电镜及傅里叶变换红外吸收光谱仪（Fourier transform infrared spectroscopy，FTIR）检测，以单纯 CMC 凝胶作为对照；取负载不同因子的 GO-CMC 凝胶行体外缓释实验。取 4～5 周龄 SPF 级 SD 雌性大鼠分离培养巨噬细胞，分别与单纯以及负载不同因子的 GO-CMC 凝胶培养，24 h 后行 CD206 免疫荧光检测巨噬细胞分化情况；取第 3 代大鼠 BMSCs 分别与单纯以及负载不同因子的 GO-CMC 凝胶成骨诱导培养，10 d 后行 ALP 染色观测早期成骨，21 d 行茜素红染色观测晚期成骨。结果大体观察 GO-CMC 凝胶呈棕色、半透明状；扫描电镜观察示，GO-CMC 凝胶孔径及孔壁厚度与单纯 CMC 凝胶相似，但内壁粗糙度增加；FTIR 检测显示 CMC 发生聚合形成凝胶。体外缓释实验示 3 种负载不同因子的 GO-CMC 凝胶缓释性能相似，均呈线性缓慢释放因子。CD206 免疫荧光检测示 GO-CMC 凝胶可诱导巨噬细胞 M2 型分化，ALP 及茜素红染色示 GO-CMC 凝胶可诱导 BMSCs 成骨分化；其中负载 IL-4+BMP-2 的 GO-CMC 凝胶作用最显著（P<0.05）。 结论负载 IL-4 和 BMP-2 的 GO-CMC 凝胶可诱导巨噬细胞 M2 型分化，增强 BMSCs 成骨分化能力，为后期骨缺损修复及骨免疫调节研究提供了新的策略。     

实时剪切波弹性成像在拉米夫定治疗乙肝纤维化过程中的疗效评估作用

目的探讨实时剪切波弹性成像在评估拉米夫定治疗乙肝纤维化临床疗效中的作用。方法选取2017年1月～2018年1月我院收治的80例乙肝纤维化患者,根据随机数字法分为对照组和观察组,每组40例。对照组采用常规治疗,观察组在对照组的基础上给予拉米夫定进行治疗,治疗6个月。比较两组治疗前后肝功能、肝纤维化指标,利用实时剪切波弹性成像评估两组治疗前后肝脏弹性模量值及肝穿刺活检情况,并进行比较。结果两组治疗后AST、ALT、TBIL水平均明显低于治疗前,差异有统计学意义(P0.05);观察组治疗后AST、ALT、TBIL水平均明显低于对照组,差异有统计学意义(P0.05);两组治疗后HA、LN、PⅢPN-P、CL-Ⅳ水平及杨氏弹性模量值均显著低于治疗前,差异有统计学意义(P0.05);观察组治疗后HA、LN、PⅢPN-P、CL-Ⅳ水平及杨氏弹性模量值均显著低于对照组,差异有统计学意义(P0.05);与治疗前相比,两组治疗后肝穿刺活检结果均有好转,尤其是汇管区、肝小叶内炎症及肝纤维化改善明显。结论实时剪切波弹性成像作为肝脏硬度定量检测的无创性技术,可用于拉米夫定治疗乙肝纤维化临床疗效评估的重要方法。     

Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance

The hepatitis C virus (HCV) is a pandemic human pathogen posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of HCV through behavioural prevention strategies has met with limited success and vaccine development remains slow. The development of antiviral therapeutic agents has also been challenging, primarily due to the lack of efficient cell culture and animal models for all HCV genotypes, as well as the large genetic diversity between HCV strains. On the other hand, the use of interferon-α-based treatments in combination with the guanosine analogue, ribavirin, achieved limited success, and widespread use of these therapies has been hampered by prevalent side effects. For more than a decade, the HCV RNA-dependent RNA polymerase (RdRp) has been targeted for antiviral development. Direct acting antivirals (DAA) have been identified which bind to one of at least six RdRp inhibitor-binding sites, and are now becoming a mainstay of highly effective and well tolerated antiviral treatment for HCV infection. Here we review the different classes of RdRp inhibitors and their mode of action against HCV. Furthermore, the mechanism of antiviral resistance to each class is described, including naturally occurring resistance-associated variants (RAVs) in different viral strains and genotypes. Finally, we review the impact of these RAVs on treatment outcomes with the newly developed regimens.     

Isolation and characterization of new human carrier peptides from two important vaccine immunogens

In the preparation of glycoconjugate vaccines in clinical practice, two highly immunogenic carrier proteins, CRM₁₉₇ and tetanus toxoid (TT), are predominantly conjugated with the capsular polysaccharides (CPSs) of bacterial pathogens. In addition, TT has long been used as an effective vaccine to prevent tetanus. While these carrier proteins play an important role in immunogenicity and vaccine design alike, their defined human major histocompatibility complex class II (MHCII) T cell epitopes are inadequately characterized. In this current work, we use mass spectrometry to identify the peptides from these carrier proteins that are naturally processed and presented by human B cells via MHCII pathway. The MHCII-presented peptides are screened for their T cell stimulation using primary CD4+ T cells from four healthy adult donors. These combined methods reveal a subset of eleven CD4+ T cell epitopes that proliferate and stimulate human T cells with diverse MHCII allelic repertoire. Six of these peptides stand out as potential immunodominant epitopes by responding in three or more donors. Additionally, we provide evidence of these natural epitopes eliciting more significant T cell responses in donors than previously published TT peptides selected from T cell epitope screening. This study serves toward understanding carrier protein immune responses and thus enables the use of these peptides in developing novel knowledge-based vaccines to combat persisting problems in glycoconjugate vaccine design.     

Cellular targets of regulatory B cell-mediated suppression

Regulatory B cells (Bregs) are defined by their ability to restrain inflammatory responses both in vivo and in vitro. Interleukin 10 (IL-10) production by Bregs is thought to be central to their ability to regulate inflammation, largely due to IL-10s’ ability to suppress pro-inflammatory cytokine production by effector lymphocytes and to maintain the differentiation of regulatory T cells (Tregs). However, with an increase in available published data, it has become evident that Bregs utilize a number of suppressive mechanisms in order to alter the activation of a variety of different lymphocytes. Here, we summarize the multiplicity of cellular targets of Breg-mediated suppression and describe the mechanisms employed by Bregs to suppress chronic inflammatory responses.