High frequency of extended-spectrum beta-lactamase-producing Enterobacteriaceae carriers at a Japanese long-term care hospital

IntroductionLong-term care hospitals (LTCHs) are at a high risk for the inflow and spread of antimicrobial resistance (AMR) pathogens. However, owing to limited laboratory resources, little is known about the extent to which AMR organisms are endemic.MethodsWe performed active surveillance for carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in newly admitted patients at Marugame Medical Center, a nearly 200-bedded LTCH located in Kagawa, Japan. From August to December 2021, we tested stool samples from patients wearing diapers and confirmed the genetic variants using specific PCR assays. We also collected clinical variables and compared them between AMR carriers and non-carriers.ResultsStool samples were collected from 75 patients, with a median age of 84 years. CRE strain was not detected, but 37 strains of ESBL-E were isolated from 32 patients (42.7%). During the study period, 4.9% of in-hospital patients (37 per 756 patients) were identified to be ESBL-E carriers in the routine microbiological processing, suggesting that active surveillance detected approximately 9-fold more ESBL-E carriers. The bla_CTX-M-9 group was the most common (38.5%), followed by the bla_TEM (26.9%). The clinical backgrounds of the ESBL-E non-carriers and carriers were not significantly different.ConclusionOur active screening demonstrated that nearly half of the patients hospitalized or transferred to a Japanese LTCH were colonized with ESBL-E. We highlight the enforcement of universal basic infection prevention techniques at LTCHs where patients carrying AMR pathogens gather.     

一测多评法同时测定艾纳香油中5种成分

目的建立一测多评法同时测定艾纳香Blumea balsamifera(L.)DC.油中β⁃蒎烯、β⁃石竹烯、樟脑、α⁃石竹烯和龙脑5种成分的含有量。方法艾纳香油乙酸乙酯提取物的分析采用PEG⁃20 M柱(30 m×0.32 mm,1.0μm);程序升温;载气为高纯氮气(99.999%);FID检测器温度240℃,进样口温度240℃。以龙脑为内标,计算其他4种成分的相对校正因子,再测定其含有量。结果蒎烯、β⁃石竹烯、樟脑、α⁃石竹烯和龙脑分别在1.49~59.5μg/mL(r=0.9996)、2.22~88.8μg/mL(r=0.9996)、6.48~259μg/mL(r=0.9997)、3.64~146μg/mL(r=0.9991)和16.4~656μg/mL(r=0.9998)范围内线性关系良好,平均加样回收率(RSD)分别为97.4%(0.9%)、99.0%(1.3%)、98.9%(0.9%)、97.6%(0.9%)和99.7%(1.0%)。一测多评法所得结果接近于外标法。结论该方法准确稳定,重复性好,可用于艾纳香油的质量控制。     

β-纤维蛋白原-455G/A基因多态性与胆囊癌的相关性研

目的 通过检测胆囊癌患者β-纤维蛋白原（Fgβ）-455G/A基因，探讨Fgβ-455G/A基因多态性与胆囊癌的相关性。方法 采集50 例胆囊癌患者（胆囊癌组）和50 例胆囊结石伴慢性胆囊炎患者（胆囊炎组）的静脉血，应用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF-MS）方法对Fgβ-455进行基因分型。 结果 Fgβ-455 基因GA杂合型和AA纯合子在胆囊癌中的频率显著高于胆囊炎组，显著增加胆囊癌发生的危险性，OR值（95%CI）分别为2.526（1.052～6.068）和4.306（1.177～15.749）。结论 Fgβ-455G/A位点G/A单个碱基的改变可能在胆囊癌的发病中起着重要的作用。     

Low-dose l-isoproterenol versus salbutamol in hospitalized pediatric patients with severe acute exacerbation of asthma: A double-blind,randomized controlled trial

BackgroundAlthough the guidelines in most countries do not recommend continuous inhalation of l-isoproterenol to treat pediatric patients with acute severe exacerbation of asthma, lower dose of l-isoproterenol has been widely used in Japan. To determine whether the efficacy of low-dose l-isoproterenol was superior to that of salbutamol, we conducted a double-blind, randomized controlled trial.MethodsHospitalized patients aged 1–17 years were eligible if they had severe asthma exacerbation defined by the modified pulmonary index score (MPIS). Patients were randomly assigned (1:1) to receive inhalation of l-isoproterenol (10 μg/kg/h) or salbutamol (500 μg/kg/h) for 12 hours via a large-volume nebulizer with oxygen. The primary outcome was the change in MPIS from baseline to 3 hours after starting inhalation. Trial registration number UMIN000001991.ResultsFrom December 2009 to October 2013, 83 patients (42 in the l-isoproterenol group and 41 in the salbutamol group) were enrolled into the study. Of these, one patient in the l-isoproterenol group did not receive the study drug and was excluded from the analysis. Compared with salbutamol, l-isoproterenol reduced MPIS more rapidly. Mean (SD) changes in MPIS at 3 hours were −2.9 (2.5) in the l-isoproterenol group and −0.9 (2.3) in the salbutamol group (difference −2.0, 95% confidence interval −3.1 to −0.9; P < 0.001). Adverse events occurred in 1 (2%) and 11 (27%) patients in the l-isoproterenol and salbutamol groups, respectively (P = 0.003). Hypokalemia and tachycardia occurred only in the salbutamol group.ConclusionsLow-dose l-isoproterenol has a more rapid effect with fewer adverse events than salbutamol.     

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

IntroductionLarge variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways.MethodsGenome Research at Fundacio ACE ([email protected]) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, [email protected] series were meta-analyzed with additional genome-wide association study data sets.ResultsWe classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444.DiscussionThe regulation of vasculature is a prominent causal component of probable AD. [email protected] meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series.     

脑淀粉样血管病发病机制的研究进展

脑淀粉样血管病（cerebral amyloid angiopathy，CAA）的主要致病物质是β淀粉样蛋白，其 产生异常、清除障碍导致异常沉积，引起管壁破坏、管腔狭窄等病理变化，最终导致CAA。目前CAA的 具体发病机制尚不清楚，涉及的成分复杂。本文介绍了β淀粉样蛋白产生及清除的三种过程及其平 衡破坏的后续效应和主要影响因素，同时从病因分类的角度阐明CAA的类型。     

糖尿病肾病患者认知功能障碍与血清β淀粉样蛋白的关系

目的 探讨糖尿病肾病(diabetic kidney disease,DKD)患者认知功能障碍与人β淀粉样蛋白1-42(human β Amyloid 1-42,Aβ1-42)的关系。方法 选取2020年5月至2021年5月在徐州医科大学附属医院内分泌科治疗的2型糖尿病(type 2 diabetes mellitus,T2DM)患者161例,根据尿白蛋白/肌酐比值(urine albumin creatine ratio,UACR)水平分为正常白蛋白尿(DM)组(n=60)、微量白蛋白尿(DKD1)组(n=58)和大量白蛋白尿(DKD2)组(n=43)。采用蒙特利尔认知评估(Montreal Cognitive Assessment,MoCA)量表评估患者认知功能。检测患者Aβ1-42、UACR、胱抑素C(Cystatin C,CysC)、估算肾小球滤过率(estimated glomerular filtration rate,eGFR),并分析上述指标与MoCA评分的关系。结果 与DM组比较,DKD1和DKD2组CysC、Aβ1-42均升高(P<0.05),eGFR降低(P<0.05)。与DKD1组比较,DKD2组CysC升高(P<0.05),eGFR降低(P<0.05)。与DM组相比,DKD1组、DKD2组MoCA评分均降低(P<0.05)。与DKD1组比较,DKD2组MoCA评分降低(P<0.05)。3组MoCA评分与Aβ1-42、UACR、CysC呈负相关(均P<0.01),与eGFR呈正相关(P<0.01)。3组Aβ1-42与UACR、CysC呈正相关(均P<0.01),与eGFR呈负相关(P<0.01)。多因素线性回归分析结果显示,Aβ1-42、UACR是影响DKD患者MoCA评分的影响因素,Aβ1-42、UACR水平越高,MoCA评分越低,患者认知功能越差。结论 DKD患者存在认知功能障碍,与Aβ1-42水平及肾损害严重程度密切相关。     

Age-related amyloidosis outside the brain: A state-of-the-art review

Inside and outside the brain, accumulation of amyloid fibrils plays key roles in the pathogenesis of fatal age-related diseases such as Alzheimer’s and Parkinson’s diseases and wild-type transthyretin amyloidosis. Although the incidence of all amyloidoses increases with age, for some types of amyloidosis aging is known as the main direct risk factor, and these types are typically diseases of elderly people. More than 10 different precursor proteins are known to cause age-associated amyloidosis; these proteins include amyloid β protein, α-synuclein, transthyretin, islet amyloid polypeptide, atrial natriuretic factor, and the newly discovered epidermal growth factor-containing fibulin-like extracellular matrix protein 1. Except for intracerebral amyloidoses, most age-related amyloidoses have been little studied. Indeed, in view of the increasing life expectancy in our societies, understanding how aging is involved in the process of amyloid fibril accumulation and the effects of amyloid deposits on the aging body is extremely important. In this review, we summarize current knowledge about the nature of amyloid precursor proteins, the prevalence, clinical manifestations, and pathogenesis of amyloidosis, and recent advances in our understanding of age-related amyloidoses outside the brain.     

Wnt/β⁃catenin信号通路参与马蹄内翻足畸形形成的研究

目的　探讨Sox9（sex determining region Y-box9）和β-catenin对先天性马蹄内翻足（congenital talipes equinovarus，CTE）的影响以及Wnt/β-catenin信号通路作用机制。 方法　将孕10 d的SD大鼠随机均分为实验组及对照组，以135 mg/kg全反式维甲酸溶于矿物油对实验组大鼠进行灌胃制作胎鼠CTE模型，对照组予以等量矿物油灌胃处理，取大鼠足踝部组织，通过免疫组化、RT-PCR、Western blot检测β-catenin、Sox9以及磷酸化β-catenin-S552的表达水平。 结果　与对照组相比，HE染色可见CTE模型组织中有较多的胶原组织沉积，免疫组化结果显示实验组标本Sox9与β-catenin表达增高，RT-qPCR表明实验组Sox9与β-catenin的mRNA水平显著增高，Western blot结果显示实验组Sox9与β-catenin的表达增高而磷酸化β-catenin-S552表达降低。 结论　CTE大鼠的足踝部组织中Sox9高表达受Wnt/β-catenin信号通路调控，该通路参与先天性马蹄内翻足畸形的形成。