特发性肺纤维化急性加重期证候与血清生物标志物的相关性研究＊

目的 通过分析特发性肺纤维化急性加重期（AE-IPF）患者证候与血清生物标志物的关系，为中医辨证治疗提供参考。方法 采用观察性研究设计，收集2019年3月至2019年11月三个中心的AE-IPF患者76例，其中痰热壅肺证26例、痰浊阻肺证50例，并纳入健康志愿者10例作为对照。采用ELISA测定患者血清CCL18、HMGB1、KL-6、MMP-7、SP-A和SP-D水平，分析与中医证候的相关性。结果 AE-IPF患者血清CCL18、HMGB1、KL-6、MMP-7、SP-A和SP-D水平均显著高于健康对照组。血清CCL18、HMGB1、KL-6、MMP-7和SP-D水平在痰热壅肺证和痰浊阻肺证患者间无显著性差异（P＞0.05），而血清SP-A水平存在显著性差异（P＜0.05）。结论 血清SP-A与AE-IPF证候存在一定的相关性，血清SP-A的浓度升高，与痰热壅肺证关系越密切，反之，血清SP-A浓度降低，则与痰浊阻肺证关系越密切。AE-IPF痰热壅肺证患者的预后可能较痰浊阻肺证患者更差。     

Total bilirubin independently predicts incident metabolic syndrome among community-dwelling women

BackgroundMetabolic syndrome (MetS) is related to the increased risk of major cardiovascular diseases (CVD). The link between high serum total bilirubin (TBL) is cross-sectionally related to MetS and its components. However, whether serum TBL predicts incidence of MetS and its components remains inconclusive.MethodsThe present study included 893 women aged 70 ± 9 years from a rural village. We examined the relationship between serum TBL and MetS based on the modified criteria of the National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP) III report in a cross-sectional (N = 893) and cohort (N = 288) data.ResultsIn the cross-sectional study, serum TBL (β = 0.536, p < 0.001) as well as age, alcohol consumption, exercise habits, history of CVD, SUA, GGT, and ALT was significantly and dependently associated with number of MetS components, but in the cohort study serum TBL was not associated with number of MetS components. Compared with the 1st tertile of serum TBL (0.20–0.55 mg/dL), multivariate-adjusted odds ratio (95% confidence interval) for the 2nd -3rd tertiles of serum TBL (0.54–2.00 mg/dL) was 0.70 (0.51–0.95) in the cross-sectional study and 0.41 (0.21–0.81) in the cohort study.ConclusionsOur data demonstrated an independently negative association between serum TBL and MetS in Japanese community-dwelling women.     

Importance of serum phosphate in elderly patients with diabetes mellitus

BACKGROUND Metabolic disturbances including changes in serum calcium,magnesium or phosphate(P) influence the prevalence of type 2 diabetes mellitus(DM).We assessed the importance of serum P in elderly patients with type 2 DM vs nondiabetes mellitus(non-DM) in relation to renal function.AIM To determine the association between serum P and serum glucose or insulin resistance in diabetic and non-diabetic patients.METHODS One hundred-ten subjects with a mean age of 69.02±14.3 years were enrolled.Twenty-nine of the participants had type 2 DM(26.4%).The incidence of hypertension,smoking and receiving vitamin D(vitD) derivates were recorded.The participants were classified by both estimated glomerular filtration rate(eGFR) and albuminuria categories according to the Kidney Disease Improving Global Outcomes 2012 criteria.RESULTS We divided the patients in two groups according to the P cut-off point related to DM value.A comparison between high and low P showed that body mass index30.2±6.3 vs 28.1±4.6(P=0.04),mean glucose 63.6 vs 50.2(P=0.03),uric acid 6.7±1.6 vs 6.09±1.7(P=0.05),mean intact-parathyroid hormone 68.06 vs 47.4(P=0.001),systolic blood pressure 147.4±16.7 vs 140..2±16.1(P=0.02),mean albuminuria 63.2 vs 50.6(P=0.04) and eGFR 45.6±22.1 vs 55.4±21.5(P=0.02)were significantly different.χ~2 tests showed a significant association between high P and DM,hypertension,receiving vitD,smoking and eGFR stage(χ~2=6.3,P=0.01,χ~2=3.9,P=0.03,χ~2=6.9,P=0.009,χ~2=7.04,P=0.01 and χ~2=7.36,P=0.04,respectively).The adjusted model showed that older age,female gender and increased body mass index were significant predictors of type 2 DM when entering the covariates.CONCLUSION High serum P contributes to vascular and metabolic disturbances in elderly patients with type 2 DM and renal impairment.     

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.     

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。     

Adaptation of Vero cells to suspension growth for rabies virus production in different serum free media

Vero cells are nowadays widely used in the production of human vaccines. They are considered as one of the most productive and flexible continuous cell lines available for vaccine manufacturing. However, these cells are anchorage dependent, which greatly complicates upstream processing and process scale-up. Moreover, there is a recognized need to reduce the costs of vaccine manufacturing to develop vaccines that are affordable worldwide. The use of cell lines adapted to suspension growth contributes to reach this objective.The current work describes the adaptation of Vero cells to suspension culture in different serum free media according to multiple protocols based on subsequent passages. The best one that relies on cell adaption to IPT-AFM an in-house developed animal component free medium was then chosen for further studies. Besides, as aggregates have been observed, the improvement of IPT-AFM composition and mechanical dissociation were also investigated.In addition to IPT-AFM, three chemically defined media (CD293, Hycell CHO and CD-U5) and two serum free media (293SFMII and SFM4CHO) were tested to set up a serum free culture of the suspension-adapted Vero cells (VeroS) in shake flasks. Cell density levels higher than 2 × 10⁶ cells/mL were obtained in the assessed conditions. The results were comparable to those obtained in spinner culture of adherent Vero cells grown on Cytodex 1 microcarriers.Cell infection with LP-2061 rabies virus strain at an MOI (Multiplicity of Infection) of 0.1 and a cell density of 8 ± 0.5 × 10⁵ cells/mL resulted in a virus titer higher than 10⁷ FFU/mL in all media tested. Nevertheless, the highest titer equal to 5.2 ± 0.5 × 10⁷ FFU/mL, was achieved in IPT-AFM containing a reduced amount of Ca⁺⁺ and Mg⁺⁺. Our results demonstrate the suitability of the obtained VeroS cells to produce rabies virus at a high titer, and pave the way to develop VeroS cells bioreactor process for rabies vaccine production.