基于文本挖掘和生物医学数据库的新型冠状病毒肺炎药物发现

目的 基于文本挖掘技术和生物医学数据库对新型冠状病毒肺炎（COVID-19）相关文献进行数据挖掘分析，探究COVID-19及其主要症状发热、咳嗽、呼吸障碍相关基因靶点，筛选潜在有效的化学药和中药。方法 使用GenCLiP 3网站获取COVID-19和其主要症状咳嗽、发热、呼吸障碍共4个关键词的共有靶点，在METASCAPE数据库中对其进行基因本体（GO）和通路富集分析，再利用String数据库和Cytoscape软件构建共有靶点的蛋白质相互作用网络，筛选获得核心基因，运用DGIdb数据库、SymMap数据库针对核心基因进行中西医治疗药物预测。结果 获得COVID-19及其主要症状共有基因靶点28个，其中有IL2、IL1B、CCL2等核心基因16个，使用DGIdb数据库筛选获得与16个关键靶点相互作用的化学药包括沙利度胺、来氟米特、环孢素等28种，中药包括虎杖、黄芪、芦荟等70味。结论 COVID-19及其主要症状的病理机制可能和CD4、KNG1、VEGFA等28个共有基因相关，可能通过介导TNF、IL-17等信号通路参与COVID-19病理过程。潜在有效药物可能通过作用相关靶点通路起到治疗COVID-19的作用。     

Clinical characteristics of pediatric patients with COVID-19 between Omicron era vs. pre-Omicron era

IntroductionDetailed data on clinical characteristics in children with the omicron strain of SARS-COV-2 are limited.MethodsWe conducted a retrospective observational study of children with COVID-19 at the National Center for Child Health and Development to evaluate the clinical manifestations during and before the emergence of the omicron variant. Only symptomatic patients without underlying diseases were included. Participants were divided into two temporal groups: the “omicron era” (1/2022–2/2022) and the “pre-omicron era,” where the delta variant predominated (7/2021–11/2021). The patients were subclassified into an older vaccine-eligible group (aged 12–17 years), a younger vaccine-eligible group (aged 5–11 years), and a vaccine-ineligible group (aged 0–4 years).ResultsWe compared 113 patients in the omicron era with 106 in the pre-omicron era. Most patients in both eras had non-severe disease, and no patients required mechanical ventilation or died. Among patients aged 0–4 years, sore throat and hoarseness were more common during the omicron era than the pre-omicron era (11.1% vs. 0.0% and 11.1% vs. 1.5%, respectively). Croup syndrome was diagnosed in all patients with hoarseness. Among patients aged 5–11 years, vomiting was more frequent during the omicron era (47.2%) than during the pre-omicron era (21.7%). Cough and rhinorrhea were less common during the omicron era in patients aged 0–4 and 5–11 years, respectively, than during the pre-omicron era.ConclusionsIn children with COVID-19, clinical manifestations differed between the omicron and pre-omicron eras. In the Omicron era, croup syndrome was more frequent in vaccine-ineligible children.     

HPRT1基因变异致Lesch-Nyhan综合征1例报告

Lesch-Nyhan综合征是一种罕见的X连锁隐性遗传病，在自伤行为出现前，易被误诊为脑瘫，延误诊治。先证者，男，8岁7个月，因发育落后8年余，肌张力异常就诊。多次血生化均提示尿酸增高，遗传学分析结果证实患儿为HPRT1基因c.200＿201delTG变异，经ACMG评级为疑似致病性变异，Sanger测序验证发现该变异遗传自患儿母亲，为未报道的新变异，从而确诊为HPRT1基因相关Lesch-Nyhan综合征，口服别嘌醇片、碳酸氢钠片6月后尿酸水平较前明显下降，仍无自伤行为。临床上遇到不明原因脑瘫表现者，应及早行遗传学检查，以帮助早期诊断和遗传咨询。     

Novel pathogenic variants in an Indian cohort with epidermolysis bullosa: Expanding the genotypic spectrum

BackgroundEpidermolysis bullosa (EB) is a genodermatosis characterized by skin fragility and blisters with variable severity. Patients with Dystrophic EB (DEB) or Junctional EB (JEB) mainly present to clinic due to greater functional impairment. Pathogenic sequence variations in COL7A1 are implicated in DEB.ObjectiveWe have tried to decipher the molecular spectrum and genotype phenotype correlation of 21 Indian patients with EB.MethodsNext generation sequencing (NGS) was performed to determine the pathogenic variants. Sanger sequencing was also done for validation of the variants in eleven individuals.ResultsPathogenic variants were detected in 20 individuals (diagnostic yield of 95%). Majority of them (90%) had sequence variation in COL7A1 while two had pathogenic variants in ITGB4 and KRT14 respectively. Out of the 18 patients confirmed to have DEB, 3 had Dominant DEB (DDEB) whereas 15 patients had Recessive DEB (RDEB). Amongst 23 sequence variations identified, 12 were found to be novel (3 were missense, 5 were premature termination codon variants while 4 were splice-site changes).ConclusionGenotype phenotype correlation was noted with milder manifestations in those with dominant inheritance types. Exact molecular diagnosis can be ascertained by NGS in majority of cases.     

布地奈德联合阿奇霉素治疗肺炎支原体肺炎

目的探讨布地奈德联合阿奇霉素治疗肺炎支原体肺炎。方法选取我院在2018年12月—2020年5月确诊并治疗的98例支原体肺炎患儿,依据不同治疗方式分成两组,两组均接受常规治疗,对照组应用阿奇霉素,研究组联合应用布地奈德。观察两组的治疗有效率水平差异;两组的康复指标:体温恢复正常耗时、缓解咳嗽气喘耗时、啰音消失耗时水平差异。结果研究组有效率水平比对照组高(P<0.05)。研究组的康复指标:体温恢复正常耗时、缓解咳嗽气喘耗时、啰音消失耗时均优于对照组(P<0.05)。结论给予支原体肺炎患儿在常规治疗基础上联合使用阿奇霉素+布地奈德,可显著提高患儿的治疗效果,缩短患儿的康复时间。     

Interoception Primes Emotional Processing: Multimodal Evidence from Neurodegeneration

Recent frameworks in cognitive neuroscience and behavioral neurology underscore interoceptive priors as core modulators of negative emotions. However, the field lacks experimental designs manipulating the priming of emotions via interoception and exploring their multimodal signatures in neurodegenerative models. Here, we designed a novel task that involves interoceptive and control-exteroceptive priming conditions followed by post-interoception and post-exteroception facial emotion recognition (FER). We recruited 114 participants, including healthy controls (HCs) as well as patients with behavioral variant frontotemporal dementia (bvFTD), Parkinson''s disease (PD), and Alzheimer''s disease (AD). We measured online EEG modulations of the heart-evoked potential (HEP), and associations with both brain structural and resting-state functional connectivity patterns. Behaviorally, post-interoception negative FER was enhanced in HCs but selectively disrupted in bvFTD and PD, with AD presenting generalized disruptions across emotion types. Only bvFTD presented impaired interoceptive accuracy. Increased HEP modulations during post-interoception negative FER was observed in HCs and AD, but not in bvFTD or PD patients. Across all groups, post-interoception negative FER correlated with the volume of the insula and the ACC. Also, negative FER was associated with functional connectivity along the (a) salience network in the post-interoception condition, and along the (b) executive network in the post-exteroception condition. These patterns were selectively disrupted in bvFTD (a) and PD (b), respectively. Our approach underscores the multidimensional impact of interoception on emotion, while revealing a specific pathophysiological marker of bvFTD. These findings inform a promising theoretical and clinical agenda in the fields of nteroception, emotion, allostasis, and neurodegeneration.SIGNIFICANCE STATEMENT We examined whether and how emotions are primed by interoceptive states combining multimodal measures in healthy controls and neurodegenerative models. In controls, negative emotion recognition and ongoing HEP modulations were increased after interoception. These patterns were selectively disrupted in patients with atrophy across key interoceptive-emotional regions (e.g., the insula and the cingulate in frontotemporal dementia, frontostriatal networks in Parkinson''s disease), whereas persons with Alzheimer''s disease presented generalized emotional processing abnormalities with preserved interoceptive mechanisms. The integration of both domains was associated with the volume and connectivity (salience network) of canonical interoceptive-emotional hubs, critically involving the insula and the anterior cingulate. Our study reveals multimodal markers of interoceptive-emotional priming, laying the groundwork for new agendas in cognitive neuroscience and behavioral neurology.     

孙丽平教授运用对药辨治小儿咳嗽临证荟萃

阐述了孙丽平教授治疗小儿咳嗽临床常用的8组对药,即前胡与白前、紫菀与款冬花、苦杏仁与桃仁、橘红与桔梗、瓜蒌与冬瓜子、地龙与僵蚕、川贝母与浙贝母、沙参与麦冬的配伍特点及临床应用心得,并列举其临证经典医案,结合中药学理论和现代药理学研究,总结分析孙教授运用对药治疗小儿咳嗽的学术经验及用药思路。孙教授认为小儿体属稚阳,其咳多起肺虚实之热,主以清热护肺,次以运脾滋阴,主次同疗,则阴阳平矣,强调小儿咳嗽用药,应以辨别个体体质差异为基础,提倡对药组方"肺脾同治、气血通调、阴阳平补"的用药理念。附案例1则,以资验证。