一例NEDD4L基因变异引起脑室旁结节状灰质异位7型患儿的临床与遗传学分析

目的对1例临床表现为全面发育迟缓、智力低下、腭裂、癫痫及四肢肌张力低下的患儿进行全外显子组测序分析,以明确其遗传学病因。方法抽取患儿及其父母外周血,提取全基因组DNA,应用二代测序技术对全外显子组基因进行变异检测、生物信息学预测分析及Sanger测序验证。结果测序结果显示患儿NEDD4L基因发生c.2117T>C(p.Leu706Pro)杂合变异,经Sanger验证患儿父母未检出该变异,为一新发变异。根据美国医学遗传学与基因组学学会(ACMG)的指南预测c.2117T>C为疑似致病性变异。结论NEDD4L基因c.2117T>C(p.Leu706Pro)变异可能为患儿的遗传学病因。     

一例手足裂胎儿的临床特征及病因学分析

目的分析一例手足裂胎儿的临床特征以及基因组拷贝数变异(copy number variations,CNVs)的情况。方法收集孕期胎儿超声以及引产儿X线检查资料并进行总结。应用二代测序(next generation sequencing,NGS)检测引产儿的CNVs。用NGS及荧光原位杂交(fluorescence in situ hybridization,FISH)对其亲代进行分析,用实时荧光定量PCR对胎儿染色体异常区域的基因表达量进行检测。结果超声及X线检查提示胎儿右手及双足均呈"V"形开裂。NGS检测提示胎儿染色体7q21.3区存在约0.36 Mb的缺失。NGS及FISH检测提示其双亲均未携带相同的变异。实时荧光定量PCR结果提示胎儿DYNC1I1基因存在杂合缺失,而SEM1、DLX5、DLX6基因的拷贝数则未见异常。结论胎儿手足裂畸形的致病原因为7q21.3区微缺失,后者为新发变异。     

A multicomponent integrative intervention to slow down the progression of mild cognitive impairment: A protocol for a randomized controlled trial

Mild cognitive impairment affects 36% of people aged 65 years and over in China, and around 50% transition from mild cognitive impairment to dementia within 3 years. Early intervention can slow down disease progression and thus delay dementia onset. The purpose of this article is to outline the protocol of an ongoing randomized controlled trial in mainland China that will evaluate the effects and feasibility of a 6-month multicomponent integrative intervention on the speed of progression of mild cognitive impairment to dementia. Ninety-six community-dwelling older adults, aged 65 years and older, will be recruited (recruitment will be completed in May 2020), using strict inclusion/exclusion criteria, from two community health service centers in Guangzhou, Guangdong province. Participants will be allocated to receive either the multicomponent integrative intervention or usual care. The core components of the intervention are cognitive training, dietary instruction, physical activity, and management of vascular risk factors. Data are collected at the beginning of the study, then at 1, 3, and 6 months. The primary outcome is cognitive function. The main secondary outcomes are exercise capacity, comprehensive physical capacity, depression, and quality of life. An intention-to-treat analysis will be conducted. The study will be completed in 2021. The multicomponent integrative intervention detailed in this protocol could be incorporated into dementia prevention programs in community health service centers, or other similar settings, to delay the onset of dementia.     

阿尔茨海默病流行现状及非药物干预研究进展

基于社区涵盖营养、运动、心理、言语及认知等多维度综合干预方式,能从认知强化、记忆改善、情绪调节、刺激神经细胞增长及自我关怀等方面综合改善阿尔茨海默病(AD)患者病情,有助于提升其生活质量,减轻患者家庭和看护者压力。本文主要阐述国内外AD流行现状及非药物干预措施,为提高老年人群生活质量提供参考。     

Progression of IgA Nephropathy under Current Therapy Regimen in a Chinese Population

Background and objectives

Current therapy for IgA nephropathy mainly includes renin-angiotensin system inhibitors and adding steroids for patients with persistent proteinuria. This study aimed to evaluate kidney disease progression and its risk factors in a Chinese cohort under current therapy.

Design, setting, participants, & measurements

Patients with IgA nephropathy followed up for at least 12 months from a prospective database were involved. Renal survival and the relationship between clinical parameters and composite kidney failure events (defined as end stage kidney failure or eGFR halving) were assessed.

Results

Overall, 703 patients between 2003 and 2011 were enrolled in this study, with a mean follow-up time of 45 months. Mean eGFR was 84.0 ml/min per 1.73 m², systolic BP was 124 mmHg, and time-averaged mean arterial pressure was 90.0 mmHg. Median proteinuria at baseline was 1.60 g/d, and time-averaged proteinuria was 0.80 g/d. The mean rate of eGFR decline was −3.12 ml/min per 1.73 m² per year (95% confidence interval, −19.07 to 11.80), and annual end stage kidney failure rate was 2.3%. Multivariate Cox regression analyses revealed that baseline eGFR (hazard ratio, 0.76 per 10 ml/min per 1.73 m²; 95% confidence interval, 0.66 to 0.91), proteinuria at 6 months (hazard ratio, 1.53 per g/d; 95% confidence interval, 1.27 to 1.84), and systolic BP control at 6 months (hazard ratio, 1.36 per 10 mmHg; 95% confidence interval, 1.05 to 1.77) were associated with composite kidney failure events. Baseline eGFR (regression coefficient, −0.06; 95% confidence interval, −0.07 to −0.04), time-averaged proteinuria (regression coefficient, −0.21; 95% confidence interval, −0.25 to −0.16), and time-averaged mean arterial pressure (regression coefficient, −0.15; 95% confidence interval, −0.21 to −0.09) were independent predictors of the slope of eGFR by linear regression.

Conclusion

Lower proteinuria and lower BP were associated with slower eGFR decline and lower risk of end stage kidney failure in patients currently being treated for IgA nephropathy.     

基于钕铁硼磁磁压榨技术在肠道吻合中的动物实验研究

目的通过建立家兔结肠的磁压榨吻合模型,验证磁压榨吻合技术在结肠压榨吻合的可行性,并评估压榨吻合口的粪便转流功能。 方法选取8只家兔,在结肠置入一定规格的磁铁实现肠道的侧侧压榨吻合,吻合口形成后,通过结肠造影、解剖观察及病理检查的方法评估吻合口的形成情况。人为结扎吻合口之间的肠道制造肠梗阻动物模型,评估压榨吻合口的粪便转流功能。 结果8只家兔均在术后第6~8天磁铁脱出;1只家兔发生肠梗阻,其余7只家兔吻合口形成良好。吻合口形成后,取3只家兔结扎吻合口之间肠道,1只家兔于术后第6天死亡,其余2只家兔长期存活,实现了压榨吻合口的粪便转流功能。 结论磁压榨吻合技术能够实现家兔肠道的吻合,是一种有效的手术方式。     

γ干扰素在特发性肺纤维化中的相关研究进展

特发性肺纤维化是一种病因不明、发病机制不清、缺乏有效治疗手段的弥漫性肺间质疾病,以肺泡上皮损伤、成纤维细胞灶形成、细胞外基质积聚,最终导致肺泡结构异常重塑为病理特征.研究发现,γ干扰素（IFN-γ）能够通过调控信号通路、调控miRNA表达、调节血管再生等发挥抗肺纤维化作用.另有文献报道,IFN-γ可能具有致炎致纤维化的作用.本文针对内源性IFN-γ在特发性肺纤维化发病过程中的作用进行综述,为特发性肺纤维化的发病和治疗提供理论依据.     

Nanocellulose supported hierarchical structured polyaniline/nanocarbon nanocomposite electrode via layer-by-layer assembly for green flexible supercapacitors

The development of a hierarchical structured multicomponent nanocomposite electrode is a promising strategy for utilizing the high efficiency of an electroactive material and improving the electrochemical performance. We propose cellulose nanofibril (CNF) aerogels with a nanoscale fiber-entangled network as the skeleton (via layer-by-layer (LbL) assembly) of electroactive materials polyaniline (PANi), carboxylic multiwalled carbon nanotubes (CMWCNTs), and graphene oxide (GO) to obtain structurally ordered polymer–inorganic hybrid nanocomposite electrodes for high-capacity flexible supercapacitors. The uniformly distributed multilayer nanoarchitecture, interconnected network, and hydrophilicity of the electrode provide a high specific surface area, excellent ion diffusion channels, and large effective contact area, thereby improving the electrochemical performance of the supercapacitor electrode. The specific capacitance of the CNF-[PANi/CMWCNT]₁₀ (CPC₁₀) and CNF-[PANi/RGO]₁₀ (CPR₁₀) electrodes reaches 965.80 and 780.64 F g⁻¹ in 1 M aqueous H₂SO₄ electrolyte, respectively; the corresponding values in PVA/H₃PO₄ electrolyte are 1.59 and 1.46 F cm⁻². In addition, the assembled symmetric supercapacitors show good energy densities of 147.23 and 112.32 mW h cm⁻², as well as excellent durability and flexibility. Our approach offers a simple and effective method for fabricating an ideal well-structured nanocomposite electrode for green and flexible energy storage devices via LbL assembly.

Cellulose nanofibril aerogel was used as a nanofibrous scaffold for layer-by-layer assembly of polyaniline and nano-carbons for flexible and high capacitance supercapacitor applications.     

基于网络药理学探讨哮喘宁颗粒防治心理应激哮喘的作用网络与潜在机制

目的 运用网络药理学研究方法探讨哮喘宁颗粒防治心理应激哮喘的作用网络与潜在机制。方法 在中药系统药理学分析平台（Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP）、中药分子机制的生物信息学分析网络（Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine,BATMAN-TCM）等数据平台筛选哮喘宁颗粒的主要有效成分与靶点;并通过相关疾病靶点数据库检索心理应激哮喘的相关靶点;通过韦恩图得到哮喘宁颗粒与心理应激哮喘之共同靶点,利用Cytoscape 3.7.2建立"药物-成分-靶点"作用网络,然后使用STRING数据库进行化合物-疾病共同靶点的蛋白互作分析（protein-protein interaction,PPI）,运用Cytoscape 3.7.2的插件MCODE、cytohubba及拓扑运算后筛选关键靶点;利用David数据库进行基因本体（Gene Ontology,GO）分析和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes,KEGG）通路富集分析。结果 筛选出哮喘宁颗粒39个主要有效成分和121个交集预测靶点,心理应激哮喘靶点1 063个;通过韦恩图得到共同靶点72个,继用cytohubba插件及拓扑运算得到重要基因,通过MCODE筛选出基因互作模块,从而得到MAPK1、MAPK8、TNF、VEGFA、EGF、PTGS2、JUN、IL-6等交集靶点;通过GO和KEGG富集分析得知这些靶点涉及信号转导、细胞增生正调控、MAPK信号通路激活等生物学过程,神经活性配体受体相互作用、TNF、NOD样受体、Toll样受体、钙离子、T细胞受体、PI3K-Akt等信号通路。结论 哮喘宁颗粒可能通过多种有效成分作用于神经机制、免疫炎性反应、细胞增生等方面以综合调节"神经-内分泌-免疫"网络,从而防治心理应激哮喘。