Identification of biomarkers for essential hypertension based on metabolomics

AimEssential hypertension (EH) is one of the most important public health problems worldwide. However, the pathogenesis of EH is unclear and early diagnostic methods are lacking. Metabolomics demonstrates great potential for biomarker discovery and the mechanistic exploration of metabolic diseases.Data synthesisThis review included human and animal metabolomics studies related to EH in the PubMed and Web of Science databases between February 1996 and May 2020. The study designs, EH standards, and reported metabolic biomarkers were systematically examined and compared. The pathway analysis was conducted through the online software MetaboAnalyst 4.0.Twenty-two human studies and fifteen animal studies were included in this systematic review. There were many frequently reported biomarkers with consistent trends (e.g., pyruvate, lactic acid, valine, and tryptophan) in human and animal studies, and thus had potential as biomarkers of EH. In addition, several shared metabolic pathways, including alanine, aspartate, and glutamate metabolism, aminoacyl-tRNA biosynthesis, and arginine biosynthesis, were identified in human and animal metabolomics studies. These biomarkers and pathways, closely related to insulin resistance, the inflammatory state, and impaired nitric oxide production, were demonstrated to contribute to EH development.ConclusionsThis study summarized valuable metabolic biomarkers and pathways that could offer opportunities for the early diagnosis or prediction of EH and the discovery of the metabolic mechanisms of EH.     

Nano-TiO2 particles impair adhesion of airway epithelial cells to fibronectin

Titanium dioxide engineered nanoparticles (nano-TiO₂) are widely used in the manufacturing of a number of products. Due to their size (<100 nm), when inhaled they may be deposited in the distal lung regions and damage Clara cells. We investigated the mechanisms by which short-term (1-h) incubation of human airway Clara-like (H441) cells to nano-TiO₂ (6 nm in diameter) alters the ability of H441 cells to adhere to extracellular matrix. Our results show that 1 h post-incubation, there was a 3-fold increase of extracellular H₂O₂, increased intracellular oxidative stress as demonstrated by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) oxidation, and a 5-fold increase of phosphor-ERK1/2 as measured by Western blotting. These changes were accompanied by a 25% decrease of H441 adherence to fibronectin (p < 0.05 compared to vehicle incubated H441 cells). Pretreatment with the ERK1/2 inhibitor U0126 for 3 h, partially prevented this effect. In conclusion, short-term exposure of H441 cells to nano-TiO₂ appears to reduce adherence to fibronectin due to oxidative stress and activation of ERK1/2.     

Propofol hemisuccinate suppression of experimental autoimmune encephalomyelitis

Propofol hemisuccinate is a prodrug water soluble form of the lipophilic, phenolic compound propofol (2,6-di-isopropylphenol), that is the active ingredient in the widely used anesthetic agent Diprovan. Propofol binds to GABA_A receptors but also has a phenolic structure that confers antioxidant properties to the molecule. The effects of propofol hemisuccinate in rat experimental autoimmune encephalomyelitis (EAE) were studied using different doses and time regimes. Propofol hemisuccinate, 100 mg/kg given three times a day from day 7 or day 12 until day 16 after disease initiation, significantly reduced maximal EAE score. Histology studies supported the clinical findings demonstrating reduction in the inflammatory response in the lumbar spinal cord in animals treated with propofol hemisuccinate. Decreased levels of nitrotyrosine and unchanged levels of induced nitric oxide synthase suggest propofol hemisuccinate crossed the blood brain barrier and exerted its effects by lowering reactive oxygen species levels. The results suggest that propofol hemisuccinate may provide an alternative mode of treatment for acute exacerbations of multiple sclerosis.     

Effect of dissolved oxygen in alcoholic beverages and drinking water on alcohol elimination in humans

Oxygen plays an important role in the metabolism of alcohol. An increased dissolved oxygen level in alcoholic beverages reportedly accelerates the elimination of alcohol. Therefore, we evaluated the effect of dissolved oxygen in alcohol and the supportive effect of oxygenated water on alcohol pharmacokinetics after the excessive consumption of alcohol, i.e., 540 ml of 19.5% alcohol (v/v). Fifteen healthy males were included in this randomized, 3 × 3 crossover study. Three combinations were tested: X, normal alcoholic beverage and normal water; Y, oxygenated alcoholic beverage and normal water; Z, oxygenated alcoholic beverage and oxygenated water. Blood alcohol concentrations (BACs) were determined by conversion of breath alcohol concentrations. Four pharmacokinetic parameters (C_max, T_max, K_el, and AUCall) were obtained using non-compartmental analysis and the times to reach 0.05% and 0.03% BAC (T_0.05% and T_0.03%) were compared using one-way analysis of variance (ANOVA) and Duncan's post hoc test. With combination Z, the BAC decreased to 0.05% significantly faster (p < 0.05) than with combination X. Analyzing the pharmacokinetic parameters, the mean K_el was significantly higher for combination Z than for combinations X and Y (p < 0.05), whereas the mean values of C_max, T_max and AUCall did not differ significantly among the combinations. Dissolved oxygen in drinks accelerates the decrease in BAC after consuming a large amount of alcohol. However, the oxygen dissolved in the alcoholic beverage alone did not have a sufficient effect in this case. We postulate that highly oxygenated water augments the effect of oxygen in the alcoholic beverage in alcohol elimination. Therefore, it is necessary to investigate the supportive effect of ingesting additional oxygenated water after heavy drinking of normal alcoholic beverages.     

Postoperative day one serum alanine amino-transferase does not predict patient morbidity and mortality after elective liver resection in non-cirrhotic patients

Serum aminotransferases have been used as sur-rogate markers for liver ischemia-reperfusion injury that fol-lows liver surgery. Some studies have suggested that rises in serum alanine aminotransferase (ALT) correlate with patient outcome after liver resection. We assessed whether postopera-tive day 1 (POD 1) ALT could be used to predict patient mor-bidity and mortality following liver resection. We reviewed our prospectively held database and included consecutive adult patients undergoing elective liver resection in our in-stitution between January 2013 and December 2014. Primary outcome assessed was correlation of POD 1 ALT with patient’s morbidity and mortality. We also assessed whether concurrent radiofrequency ablation, neoadjuvant chemotherapy and use of the Pringle maneuver signiifcantly affected the level of POD 1 ALT. A total of 110 liver resections were included in the study. The overall in-hospital patient morbidity and mortality were 31.8% and 0.9%, respectively. The median level of POD 1 ALT was 275 IU/L. No correlation was found between POD 1 serum ALT levels and patient morbidity after elective liver resection, whilst correlation with mortality was not possible because of the low number of mortalities. Patients undergoing concur-rent radiofrequency ablation were noted to have an increased level of POD 1 serum ALT but not those given neoadjuvant chemotherapy and those in whom the Pringle maneuver was used. Our study demonstrates POD 1 serum ALT does not cor-relate with patient morbidity after elective liver resection.     

基于救护车车载氧气瓶柜的优化安装设计

目的：设计一种全新的车载氧气瓶柜安装方式，对救护车医疗舱的空间资源进行重新整合，以增加抢救设备的安装空间，避免更换氧气瓶时的倾倒、坠落而导致的人员受伤甚至是爆炸事故的发生，提高安全性。方法：用可开关的合页将旋转式氧气瓶柜固定于救护车尾部的垂直上车扶手的下部、上车担架的对侧。结果：旋转式车载氧气瓶柜避免了先前更换氧气瓶的种种安全隐患，大大降低了医务工作者的劳动强度。结论：旋转式车载氧气瓶柜将成为未来救护车主流改装趋势。     

2型糖尿病患者自体血细胞葡萄糖细胞膜转运研究

目的对2型糖尿病(T2DM)患者自体血细胞葡萄糖细胞膜转运进行研究。方法 T2DM组(40例)、T2DM前期组(前期组,34例)、对照组(40例)抗凝全血分别加入同体积生理盐水和ATP,37℃水浴3h,观察葡萄糖水平变化,计算葡萄糖下降值和下降比例。结果组内比较,加ATP管葡萄糖下降值高于盐水管(P0.01)。组间比较,盐水管葡萄糖下降比例,T2DM组、前期组、对照组依次增加,T2DM组低于对照组(P0.01),T2DM组低于前期组(P0.05)。ATP管葡萄糖下降比例,T2DM组低于对照组(P0.05)。T2DM患者加ATP后葡萄糖下降值由盐水管的(2.81±0.52)mmol/L增加到(4.73±0.69)mmol/L。结论 T2DM患者存在葡萄糖细胞膜转运障碍,与病程进展相关,ATP能够改善葡萄糖的细胞膜转运。     

Biomechanical,metabolic and cardiopulmonary responses of masters recreational runners during running at different speeds

This study tested interactions between age and running speed on biomechanics, metabolic responses and cardiopulmonary responses. Three-hundred participants ran at preferred and standardized speeds. Age group (younger, masters [≥40 years]) by speed (self-selected 8.8 km/h, 11.2 km/h and 13.6 km/h) interactions were tested on main outcomes of sagittal kinematic, temporal spatial, metabolic and cardiopulmonary parameters. At all speeds, angular displacements of the ankle, pelvis and knee were less in masters than younger runners (Hedges g effect size range = 0.30–1.04; all p < 0.05). A significant age group by speed interaction existed for hip angular displacement (Wald χ² = 10.753; p = 0.013). Masters runners ran at higher relative heart rates (p < 0.05) but at similar rates of oxygen use and energy expenditure. Masters runners used hip-dominant motion and step lengthening as running speed increased, but did not change centre of mass vertical displacement. This may increase mechanical stresses on tissues of the lower extremity in masters runners, especially hamstrings, hip joint and Achilles.