高糖饮食对小鼠真菌性角膜炎的影响

目的　探究高糖饮食对小鼠真菌性角膜炎的影响。方法　选取健康无眼疾的雄性C57BL/6J小鼠78只，随机分为高糖饮食组和模型对照组，每组36只，模型对照组给予正常饮用水，高糖饮食组给予含体积分数10%果糖溶液，每2 d测量两组小鼠体质量及血糖，10 d后建立真菌性角膜炎模型。造模后24 h、36 h、48 h、72 h、96 h、120 h、168 h裂隙灯显微镜下对角膜进行临床评分并拍照。处死小鼠后，取角膜组织进行HE染色和PAS染色；测定角膜内中性粒细胞和巨噬细胞浸润体积。利用酶联免疫吸附实验对小鼠角膜内的白细胞介素-1β含量进行测定。结果　造模后 0~14 d，两组小鼠体质量与血糖差异均无统计学意义（均为P>0.05）。造模后24 h、36 h、48 h、120 h、168 h，高糖饮食组小鼠角膜临床评分均明显高于模型对照组，差异均有统计学意义（均为P<0.05）。高糖饮食组小鼠角膜穿孔率79.5%，高于模型对照组的40.9%，差异有统计学意义（P=0.000）。造模后各时间点，高糖饮食组中性粒细胞浸润体积均高于模型对照组，差异均有统计学意义（均为P=0.000）。造模后72 h、96 h、120 h、168 h，高糖饮食组巨噬细胞浸润体积均高于模型对照组（均为P=0.000）。角膜组织病理学检查结果示，高糖饮食组炎症反应更重，角膜组织破坏更早且更为严重。造模后24 h、48 h高糖饮食组白细胞介素-1β含量均明显高于模型对照组（均为P<0.05）。结论　高糖饮食加重了真菌性角膜炎感染的严重程度，增强了中性粒细胞、巨噬细胞的趋化，促进了IL-1β的分泌。     

In vivo epigenetic effects induced by engineered nanomaterials: A case study of copper oxide and laser printer-emitted engineered nanoparticles

Evidence continues to grow on potential environmental health hazards associated with engineered nanomaterials (ENMs). While the geno- and cytotoxic effects of ENMs have been investigated, their potential to target the epigenome remains largely unknown. The aim of this study is two-fold: 1) determining whether or not industry relevant ENMs can affect the epigenome in vivo and 2) validating a recently developed in vitro epigenetic screening platform for inhaled ENMs. Laser printer-emitted engineered nanoparticles (PEPs) released from nano-enabled toners during consumer use and copper oxide (CuO) were chosen since these particles induced significant epigenetic changes in a recent in vitro companion study. In this study, the epigenetic alterations in lung tissue, alveolar macrophages and peripheral blood from intratracheally instilled mice were evaluated. The methylation of global DNA and transposable elements (TEs), the expression of the DNA methylation machinery and TEs, in addition to general toxicological effects in the lung were assessed. CuO exhibited higher cell-damaging potential to the lung, while PEPs showed a greater ability to target the epigenome. Alterations in the methylation status of global DNA and TEs, and expression of TEs and DNA machinery in mouse lung were observed after exposure to CuO and PEPs. Additionally, epigenetic changes were detected in the peripheral blood after PEPs exposure. Altogether, CuO and PEPs can induce epigenetic alterations in a mouse experimental model, which in turn confirms that the recently developed in vitro epigenetic platform using macrophage and epithelial cell lines can be successfully utilized in the epigenetic screening of ENMs.     

Population Genetics Identifies Challenges in Analyzing Rare Variants

Geneticists have, for years, understood the nature of genome‐wide association studies using common genomic variants. Recently, however, focus has shifted to the analysis of rare variants. This presents potential problems for researchers, as rare variants do not always behave in the same way common variants do, sometimes rendering decades of solid intuition moot. In this paper, we present examples of the differences between common and rare variants. We show why one must be significantly more careful about the origin of rare variants, and how failing to do so can lead to highly inflated type I error. We then explain how to best avoid such concerns with careful understanding and study design. Additionally, we demonstrate that a seemingly low error rate in next‐generation sequencing can dramatically impact the false‐positive rate for rare variants. This is due to the fact that rare variants are, by definition, seen infrequently, making it hard to distinguish between errors and real variants. Compounding this problem is the fact that the proportion of errors is likely to get worse, not better, with increasing sample size. One cannot simply scale their way up in order to solve this problem. Understanding these potential pitfalls is a key step in successfully identifying true associations between rare variants and diseases.     

基于证候要素的中风辨证论治

中风病是临床的常见病、多发病。本病病因较多,病情变化迅速,证型繁杂,不同的文献中证候分类差异较大。证候分类的繁杂给临床工作者治疗中风病带来极大不便。本文对以证候要素(内风、内火、痰湿、瘀血、气虚、阴虚)为切入点论治中风病的理论进行探讨,并举例论证其临床疗效。     

糖尿病前期中医证型及证素特点分析＊

目的 探讨糖尿病前期的中医证型及证素分布特点。方法 检索中国知网、万方及维普三大数据库中收录的自建库以来有关糖尿病前期证型的临床研究文献，对中医证型进行规范整理，建立数据库，提取证素，运用数据挖掘技术中的关联分析、聚类分析探究证素分布规律。结果 共纳入10篇文献，总有效病例1620例，证型经规范处理后整理为18个，主要证型为脾虚痰湿证。共提取证素13个，主要病位证素为脾，主要病性证素为气虚、湿和痰，关联分析显示脾—湿支持度和置信度最高，聚类分析结果可得到3个聚类组。结论 糖尿病前期病位在脾，气虚、脾、痰、湿是常见证素，临床诊治糖尿病前期应注重从脾论治，需辨证施治。     

Germline gain-of-function MMP11 variant results in an aggressive form of colorectal cancer

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.     

Adherence to the Mediterranean diet and weight status in children: the role of parental feeding practices

Abstract

The study examines Parental Feeding Practices (PFP) in relation to adherence to the Mediterranean Diet (MD) and children’s weight status. It’s a cross-sectional study of 402 parents (68.4% mothers), with children aged 2–12 years. Parents completed the Comprehensive Parental Feeding Questionnaire and the Mediterranean Diet Quality Index for children and adolescents (KIDMED), evaluating children’s adherence to the MD. Logistic regression showed that in children aged 2–<6 years, “emotion regulation/food as reward” and “pressure” decrease MD adherence (OR?=?0.186, p?<?0.0001 and OR?=?0.496, p?=?0.004), and “monitoring” decrease excess body weight (OR?=?0.284, p?=?0.009). In older children (6–12 years), “healthy eating guidance” and “monitoring” increase MD adherence (OR?=?3.262, p?=?0.001 and OR?=?3.147, p?<?0.0001), “child control” decreases MD adherence (OR?=?0.587, p?=?0.049), “pressure” decrease excess body weight (OR?=?0.495, p?<?0.0001) and “restriction” increase excess body weight (OR?=?1.784, p?=?0.015). “Healthy eating guidance” and “monitoring” seem to be the best PFP employed, in terms of children’s MD adherence and weight status.