Protection of White Leghorn chickens by recombinant fowlpox vector vaccine with an updated H5 insert against Mexican H5N2 avian influenza viruses

Despite decades of vaccination, surveillance, and biosecurity measures, H5N2 low pathogenicity avian influenza (LPAI) virus infections continue in Mexico and neighboring countries. One explanation for tenacity of H5N2 LPAI in Mexico is the antigenic divergence of circulating field viruses compared to licensed vaccines due to antigenic drift. Our phylogenetic analysis indicates that the H5N2 LPAI viruses circulating in Mexico and neighboring countries since 1994 have undergone antigenic drift away from vaccine seed strains. Here we evaluated the efficacy of a new recombinant fowlpox virus vector containing an updated H5 insert (rFPV-H5/2016), more relevant to the current strains circulating in Mexico. We tested the vaccine efficacy against a closely related subcluster 4 Mexican H5N2 LPAI (2010 H5/LP) virus and the historic H5N2 HPAI (1995 H5/HP) virus in White Leghorn chickens. The rFPV-H5/2016 vaccine provided hemagglutinin inhibition (HI) titers pre-challenge against viral antigens from both challenge viruses in almost 100% of the immunized birds, with no differences in number of birds seroconverting or HI titers among all tested doses (1.5, 2.0, and 3.1 log₁₀ mean tissue culture infectious doses/bird). The vaccine conferred 100% clinical protection and a significant decrease in oral and cloacal virus shedding from 1995 H5/HP virus challenged birds when compared to the sham controls at all tested doses. Virus shedding titers from vaccinated 2010 H5/LP virus challenged birds significantly decreased compared to sham birds especially at earlier time points. Our results confirm the efficacy of the new rFPV-H5/2016 against antigenic drift of LPAI virus in Mexico and suggest that this vaccine would be a good candidate, likely as a primer in a prime-boost vaccination program.     

高乳酸血症-卒中样发作综合征型线粒体脑肌病一家系两代四例报告

线粒体脑肌病属于罕见性母系遗传病，本文回顾性分析了1家4例高乳酸血症-卒中样发作综合征（MELAS）型线粒体脑肌病患者，其主要表现为卒中样发作、头痛、癫痫、高乳酸血症、肌肉不耐受疲劳、高级智能下降、听力下降和身材矮小等，结合特征性影像学变化、基因检测及肌肉活检明确诊断，并结合文献对只有女儿能将其线粒体DNA（mt-DNA）传递给下一代的母系遗传MELAS型线粒体脑肌病临床特点进行了总结分析，旨在帮助临床认识此病，进一步提高MELAS型线粒体脑肌病的临床诊断率。     

Biasing human epidermal growth factor receptor 4 (HER4) tyrosine kinase signaling with antibodies: Induction of cell death by antibody‐dependent HER4 intracellular domain trafficking

Human epidermal growth factor receptor 4 (HER4) isoforms have oncogenic or tumor suppressor functions depending on their susceptibility to proteolytic cleavage and HER4 intracellular domain (4ICD) translocation. Here, we report that the neuregulin 1 (NRG1) tumor suppressor mechanism through the HER4 JMa/CYT1 isoform can be mimicked by the agonist anti‐HER4 Ab C6. Neuregulin 1 induced cleavage of poly(ADP‐ribose) polymerase (PARP) and sub‐G₁ DNA fragmentation, and also reduced the metabolic activity of HER3^?/HER4⁺ cervical (C‐33A) and ovarian (COV318) cancer cells. This effect was confirmed in HER4 JMa/CYT1‐, but not JMa/CYT2‐transfected BT549 triple‐negative breast cancer cells. Neuregulin 1 favored 4ICD cleavage and retention in mitochondria in JMa/CYT1‐transfected BT549 cells, leading to reactive oxygen species (ROS) production through mitochondrial depolarization. Similarly, the anti‐HER4 Ab C6, which binds to a conformational epitope located on a.a. 575‐592 and 605‐620 of HER4 domain IV, induced 4ICD cleavage and retention in mitochondria, and mimicked NRG1‐mediated effects on PARP cleavage, ROS production, and mitochondrial membrane depolarization in cancer cells. In vivo, C6 reduced growth of COV434 and HCC1187 tumor cell xenografts in nude mice. Biasing 4ICD trafficking to mitochondria with anti‐HER4 Abs to mimic NRG1 suppressor functions could be an alternative anticancer strategy.     

妊娠期糖尿病孕妇血糖和体重控制情况研究

目的探讨系统化血糖及体重控制对妊娠期糖尿病孕妇妊娠结局的影响。方法选择2018年1月-2019年1月中山大学附属第三医院粤东医院收治的100例妊娠期糖尿病孕妇作为研究对象,按护理方式的不同分为观察组和对照组各50例。对照组接受常规治疗及饮食指导干预,观察组在对照组基础上进行系统化血糖和体重控制干预。比较两组孕妇餐前空腹血糖、体重控制情况及母婴并发症发生情况。结果观察组孕妇的血糖及体重控制情况优于对照组,且观察组孕妇及围生儿并发症的发生率低于对照组,差异均有统计学意义(P<0.05)。结论接受系统化血糖及体重控制的妊娠期糖尿病孕妇取得的效果较好,其血糖和体重指数控制较好,母婴并发症少,具有临床推广价值。     

抗中性粒细胞胞浆抗体在儿童闭塞性细支气管炎病情评估中的价值

目的 探讨抗中性粒细胞胞浆抗体（ANCA）在儿童闭塞性细支气管炎（BO）病情评估中的临床价值。方法 前瞻性选取2009年6月至2014年10月诊断为BO的患儿59例为研究对象，应用酶联免疫吸附法检测患儿血清中的髓过氧化物酶（MPO）及蛋白酶3（PR3）ANCA的浓度，根据其结果将患儿分为ANCA双阴性组（n=22）、ANCA单阳性组（n=17）及ANCA双阳性组（n=20）。比较入院时各组患儿的BO发生危险因素、临床症状、胸部高分辨CT（HRCT）及肺部病理学评分，以及ANCA表达水平及临床症状、胸部HRCT评分随时间的变化。结果 ANCA双阳性组患儿的BO危险因素评分明显高于ANCA双阴性组（P < 0.05），ANCA单阳性组及双阳性组的临床症状、胸部HRCT及肺部病理学评分均高于ANCA双阴性组（P < 0.05）。患儿出院后随访6个月，MPO-ANCA、PR3-ANCA滴度水平均较入院时和出院时降低（P < 0.05）；其临床症状评分亦低于入院时（P < 0.05），但胸部HRCT评分与入院时比较差异无统计学意义（P > 0.05）；ANCA单阳性组及双阳性组的临床症状评分仍高于ANCA双阴性组（P < 0.05）。结论 ANCA表达水平与BO患儿的病情严重程度具有相关性，对病情评估有一定的临床意义。     

Long-Term Clinical Outcomes after Endovascular Therapy for Anti-Centromere Antibody-Positive Patients with Critical Limb-Threatening Ischemia

PurposeTo examine the long-term clinical outcomes of patients with anti-centromere antibody (ACA)-positive critical limb-threatening ischemia (CLTI) who were treated with endovascular therapy (EVT).Materials and MethodsThis was a retrospective analysis using a database of 423 consecutive CLTI patients (543 limbs, Rutherford class 4–6) who underwent EVT between January 2011 and March 2013. The patients were divided into 2 groups: an ACA-positive group (10 limbs, 8 patients) and a control group (46 limbs, 43 patients). The control group was defined as female, non-dialysis, and those who were able to obtain a below-knee angiogram.ResultsNone of the 8 ACA-positive CLTI patients had previously been diagnosed as ACA positive. No significant difference was observed in the below-the-knee lesion distribution and severity between the ACA-positive group and the control group. The median observational period was 51 months. The survival rate was 54% in the ACA-positive group and 76% in the control group at 5 years after EVT (P = .732). The freedom from major amputation rate was 60% in the ACA-positive group and 91% in the control group at 5 years after EVT (P = .029). The technical EVT success rate in the ACA-positive group was 70% (7/10). Of the successful EVT cases, 71% (5/7) of patients achieved complete wound healing or rest pain relief; however, 60% (3/5) had a recurrence of wounds.ConclusionsIn a series of ACA-positive patients with CLTI, successful EVT had acceptable outcomes with respect to wound healing with short-term results. However, the major amputation rate for ACA-positive patients was high in long-term follow-up.     

Regional variations in the use of postnatal care in Nigeria: a spatial analysis

ABSTRACT

Maternal health outcomes vary considerably in Nigeria, with maternal mortality ratio ranging from 165 per 100,000 live births in the South-west to 1549 per 100,000 live births in the North-east. One important maternal health indicator is an adequate use of postnatal care (PNC); however, the evidence is sparse on its spatial distribution across regions in Nigeria. This paper thus examined the spatial distribution of uptake of postnatal care in Nigeria using data from the 2013 Nigeria Demographic and Health Survey, with a sample of 12,127 women aged 15–49 years. The Bayesian-structured additive regression of the logit model was used to examine the spatial relationships. The results revealed a north-south divide in the use of postnatal care, with higher PNC uptake established in the latter. Interestingly, results showed significant intra-region residual spatial variations with higher PNC use in Yobe and Bauchi in North-east Nigeria compared to other states within the region. The findings indicate the need for policymakers to develop state- and region-specific health policy and intervention programs to address the inequity in postnatal care coverage and usage across regions in Nigeria.     

单抗N糖分析系统适用性对照品的建立

目的建立单抗N糖分析方法的系统适用性对照品,并设定相应的系统适用性要求。方法利用液质联用(LC-MS)仪对N糖系统适用性对照品进行N糖型的表征鉴别,并对对照品进行稳定性评价。结合方法特点和验证数据,对系统适用性要求进行设定。结果建立的系统适用性对照品具有良好的稳定性,其糖型涵盖了单抗主要的N糖型种类。针对3种药典拟收录的单抗N糖分析方法,设定了以下系统适用性要求,包括:图谱与典型图谱相似、G1F(1,6)和G1F(1,3)的分离度应满足具体要求、G0F%应在规定的范围内、G0F保留时间的RSD应≤4%。结论建立了单抗N糖系统适用性对照品,可配合3种2020年版《中国药典》拟收录的N糖分析方法使用。