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。     

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。     

乳腺癌缺氧诱导因子-1α、Ki-67表达与超声声像特征的关系

目的探讨乳腺癌患者乳腺癌组织中的缺氧诱导因子-1α(HIF-1α)、Ki-67蛋白的表达与超声声像特征的关系。方法对110例乳腺癌患者进行超声检查,观察患者的毛刺征、肿块形态、钙化灶形态和血流显像分级等。取110例乳腺癌患者的乳腺癌组织,免疫组化法检测HIF-1α、Ki-67蛋白的阳性表达率。分析不同超声声像特征乳腺癌患者乳腺癌组织中HIF-1α、Ki-67蛋白的表达情况。结果110例乳腺癌患者中,43例既存在Ki-67蛋白阳性表达又存在HIF-1α蛋白阳性表达,35例仅存在Ki-67蛋白阳性表达,13例仅存在HIF-1α蛋白阳性表达,Ki-67、HIF-1α蛋白阴性表达患者共19例。乳腺癌患者乳腺癌组织中Ki-67蛋白的阳性表达率为70.91%(78/110),HIF-1α蛋白的阳性表达率为50.91%(56/110)。不同肿块形态、钙化灶形态、血流显像分级乳腺癌患者乳腺癌组织中Ki-67蛋白阳性表达率比较,差异均有统计学意义(P﹤0.05)。不同血流显像分级乳腺癌患者乳腺癌组织中HIF-1α蛋白阳性表达率比较,差异有统计学意义(P﹤0.05)。结论乳腺癌患者乳腺癌组织中HIF-1α的表达可能与血流显像分级有关,Ki-67的表达可能与肿块形态、钙化灶形态及血流显像分级有关。     

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.     

地黄饮子加减方对血管性痴呆模型大鼠学习记忆能力及海马CA1区神经元损伤的影响

目的:观察地黄饮子加减方对血管性痴呆模型大鼠学习记忆能力及海马CA1区神经元的影响。方法:将84只SD雄性大鼠,按随机原则选出12只大鼠作为假手术组,其余72只大鼠采用两血管阻断法制备血管性痴呆模型,筛选60只模型大鼠,每组12只,随机分为模型组,尼莫地平组(0. 011 g·kg~(-1)),地黄饮子加减方高、中、低(4. 54,2. 27,1. 14 g·kg~(-1))剂量组。连续灌胃30 d后,Morris水迷宫检测大鼠学习记忆能力,苏木素-伊红(HE)观察海马CA1区神经元形态结构改变,透射电镜观察海马CA1区神经元超微结构变化,原位细胞凋亡检测法(TUNEL)检测海马CA1区细胞凋亡水平,免疫组化(IHC)检测海马CA1区组织磷脂酰肌醇3-激酶(PI3K),蛋白激酶B(Akt),半胱氨酸蛋白酶-3(Caspase-3)表达水平。结果:与假手术组比较,模型组大鼠逃避潜伏期显著延长,穿越原平台次数显著减少(P 0. 01),海马CA1区神经元形态均有不同程度地损伤,凋亡率显著增加(P 0. 01),PI3K,Akt的积分吸光度和平均积分吸光度明显降低(P 0. 01),Caspase-3的积分吸光度和平均积分吸光度显著增高(P 0. 01);与模型组比较,各给药组大鼠逃避潜伏期缩短(P 0. 05,P 0. 01),穿越原平台次数增加(P 0. 05,P 0. 01),PI3K,Akt的积分吸光度和平均积分吸光度值显著增高(P 0. 01),Caspase-3的积分光密度和平均积分吸光度不同程度降低(P 0. 05,P 0. 01)。结论:地黄饮子加减方可改善血管性痴呆模型大鼠学习记忆能力和海马CA1区神经元损伤,潜在机制可能与PI3K/Akt信号转导途径的激活,抑制大鼠海马CA1区神经细胞的凋亡有关。     

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.