COX20基因变异线粒体复合物Ⅳ缺乏症相关的遗传性周围神经病4例病例系列报告及文献复习

背景：原发性线粒体病具有高度的临床和遗传异质性，其中周围神经是线粒体病的常见受累器官之一。 目的：总结COX20基因变异相关周围神经病的临床表型及遗传学特征。 设计：病例系列报告。 方法：回顾性收集2018年5月至2020年5月复旦大学附属儿科医院诊治的COX20基因变异相关周围神经病患儿的临床资料，总结其临床表现、基因检测结果及治疗效果，并以“COX20”、“线粒体复合物Ⅳ缺乏症（Complex Ⅳ deficiency）”为关键词检索中英文数据库。检索时间均为从建库至2021年12月。总结已报道COX20基因变异与临床表型的关系。 主要结局指标：临床表型和COX20基因变异位点。 结果：4例患儿纳入分析，男、女各2例，其中3例自幼运动发育落后。4例均在儿童期起病，均以行走不稳为首发症状。肌电图均提示多发性周围神经损害改变，感觉神经轴索受累为主。4例患儿均携带COX20基因复合杂合变异，包括错义变异2个，无义变异和移码变异各1个，其中移码变异c.262delG(p.E88Kfs*35)尚未见报道。文献复习目前共报道COX基因变异18个家系22例患儿（包括本文病例）,起病中位年龄为5（1.0~17）岁，22例均以行走困难或步态不稳起病，11例（50.0%）有精神运动发育迟滞，病程中14例(63.6%)出现构音障碍，14例(63.6%)出现肌力下降和/或足部畸形，8例（36.4%）出现共济失调，6例(27.3%)出现肌张力障碍，5例（22.7%）存在认知倒退等。21例患儿行神经传导及肌电图检查，19例(90.5%)提示多发性周围神经病变。头颅（18例）及脊髓（10例）MR检查提示，脊髓萎缩4例（40%），小脑萎缩4例（22.2%）。9例患儿已无法独立行走，丧失独立行走能力中位年龄为10（7~21）岁。目前共报道9个变异位点，4种变异类型，其中错义变异5个，剪切变异2个，无义变异和移码变异各1个。 结论：COX20基因变异患者多早期起病，以周围神经系统病变为主要表现，可合并构音障碍、共济失调、肌张力障碍、认知倒退等，病情逐渐进展，致残率高。COX20基因变异类型以错义变异最常见。     

Constructing robust selves after brain injury: positive identity work among members of a female self-help group

Despite common experiences of identity damage, decline, and deterioration, many brain injury survivors succeed in reconstructing robust identities in the wake of injury. Yet, while this accomplishment greatly benefits survivors’ quality of life, little is known about how positive identity work might be facilitated or enhanced in therapeutic institutions. Drawing on data from a women’s self-help group, we argue that an egalitarian, reflective, strength-focused, and gender-segregated environment can provide female ABI (acquired brain injury) survivors with a fertile scene for identity enhancement and offer unique opportunities for collective identity development. Sociolinguistic interactional analysis revealed four types of positive identity work undertaken within the group: constructing competent selves; tempering the threat of loss and impairment; resisting infantilisation and delegitimisation; and asserting a collective gender identity. This identity work was facilitated by specific programme attributes and activities and contributed to the global project of decentring disability and destigmatising impairments and losses. We call for increased attention to identity issues in brain injury rehabilitation and argue that gender-segregated programming can provide a unique space for female survivors to construct empowering individual and collective identities after injury.     

A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.     

抗PD-(L)1、抗CTLA-4免疫治疗标志物研究进展

免疫检查点抑制剂已经改变了包括肺癌、黑色素瘤等许多肿瘤的治疗情况，并且在一些难治性肿瘤中表现出持久的应答率，然而在部分接受治疗的患者中表现出无反应及严重免疫相关副作用。为了优化免疫疗法的使用，可能需要多种临床应答的预测性标志物。本研究回顾了几种潜在有效生物标志物的可用数据，通过免疫组化检测肿瘤细胞和免疫细胞中PD-L1的表达，提示其是一种临床疗效的良好预测标志物;且PD-L1表达阴性者经免疫治疗后仍可获益。PD-L1表达在肿瘤内是动态和异质性的:在原发性灶和转移灶之间或在穿刺标本和大体标本之间表达不一致。肿瘤突变负荷与新抗原的高比率可获得持久获益。外周血标志物也可作为潜在标志物，增加的绝对淋巴细胞计数（ALC）与疾病控制和生存显著相关。在这篇综述中，我们旨在讨论抗PD-（L）1与抗CTLA-4 免疫治疗相关标志物研究现状，为临床运用提供指导，以便能够准确筛选出从这些治疗中获益更多的患者。     

中医气郁质的研究进展

体质是在先天遗传和后天获得共同影响下形成的个体在形态结构和功能活动方面所固有的、相对稳定的特点,并且与心理性格具有相关性。其中气郁质的表现多与心理性格具有较大的相关性,同时由于当代社会的快速发展,各种危机和压力使年轻人成为气郁质的高发人群,因此探究气郁质的相关研究具有重大意义。本文通过对近些年来所发表的气郁质相关文献进行总结,重点从气郁质的人群分布调查研究、体病相关研究、调体干预研究以及实验室相关指标的研究四个方面进行分析阐述。最后对目前关于气郁质的研究中存在的优点和不足进行思考,并提出气郁质研究应在中医理论为指导的基础上,通过现代分子生物学实验或临床干预调体研究,揭示气郁质的本质和其量化诊疗标准,丰富气郁质的理论数据支持,促进中医体质学与多学科的交互发展。     

Evidence-based pediatric asthma interventions and outcome measures in a healthy homes program: An integrative review

Objective: Asthma disproportionately impacts and has poorer outcomes in low-income, minority, and inner-city children. The home environment has a profound impact on a child's asthma. Home-based asthma visits have the potential to positively impact a child's asthma, especially in targeted populations. The purpose of this integrative review is 1.) to explore the effectiveness of home-based education and environmental measures and 2.) to explore specific indicators and tools to measure pediatric asthma control and program effectiveness. Data Sources: Medline, CINHAL, and Ovid databases were searched from 2010 to 2017 utilizing the keywords healthy homes AND asthma and home based interventions AND asthma. Study Selections: A total of 71 articles were retrieved of which 27 articles met the inclusion criteria of English language, human subjects, and the inclusion of pediatric populations. Three additional articles were hand-searched from previous references. In total, 30 articles were reviewed. A quality appraisal was conducted utilizing standardized appraisal tools. Results: Home-based asthma education and environmental interventions have proven to be effective. The programs reviewed varied in types of interventions, intensity and duration, the type of provider, length of follow-up, and outcome measures. Successful programs were patient-centered, included a home assessment and individualized education and interventions, and were collaborative. Multiple outcome indicators such as health care utilization, asthma control, missed days of school or productivity, asthma symptoms, and verification of environmental remediation have been utilized. Conclusion: Home-based asthma programs can be beneficial to children with poorly controlled asthma and have the potential to be cost-effective.     

Qigong in the treatment of children with autism spectrum disorder: A systematic review

BackgroundAutism spectrum disorder is a condition that affects all races, ethnic and socioeconomic groups. With a high incidence ratio of one in every 68, it has become one of the most discussed psychiatric disorders. For this reason, the need for investigating novel treatments has been emerging. Qigong, a traditional Chinese mind-body technique, has already proven to be able to reduce symptoms of several physical and psychological illnesses.ObjectiveThe purpose of this systematic review is to examine and categorize the current scientific evidence regarding the efficacy of Qigong on children suffering from autism spectrum disorders.Search strategyA systematic literature search of the electronic scientific databases PubMed, Clinical Trials.gov, BioMed Central, PubMed Central and Google Scholar was performed to identify studies of Qigong in the treatment of children with autism spectrum disorder.Inclusion criteriaThis review included randomized controlled trials, replication studies, retrospective studies and observational follow-up studies of Qigong on children with autism spectrum disorder. Case reports and case series were excluded.Data extraction and analysisTwo researchers independently evaluated the methodological quality of all included studies. Any discrepancies were solved by discussion until consensus was achieved.ResultsOur literature search identified 157 publications, and 10 additional publications from hand search of references. After duplicate removal, 103 records remained. After the title/abstract screening, 19 publications were obtained for detailed evaluation. After detailed evaluation, 10 studies were included. Seven studies were conducted with small children with 2–6 years old employing Qigong massage, and three studies were conducted with older children aged 7–17 years old applying both Qigong massage (one study) and Neigong (two studies).ConclusionStudies demonstrated that Qigong has interesting and promising applicability and effect on children with autism spectrum disorder and should be tested further. Despite the need for more rigorous controlled studies, Qigong seems to be able to decrease severity of individual sensory, behavioural, and language components of autism, and improve self-control, sociability, sensory and cognitive awareness as well as healthy-physical behaviour. Besides positive effect on children and adolescents, benefits seem to extend to parents and caregivers as well. However, quality of methodology seems to be insufficient to state that Qigong is an alternative to common behavioural therapies. We suggest that, until more investigation is performed, Qigong may only be used as a complement, or when behavioural therapies are not accessible.