Bioimaging of multiple elements by high‐resolution LA‐ICP‐MS reveals altered distribution of mineral elements in the nodes of rice mutants

Inter‐vascular transfer in rice (Oryza sativa) nodes is required for delivering mineral elements to developing tissues, which is mediated by various transporters in the nodes. However, the effect of these transporters on distribution of mineral elements in the nodes at a cellular level is still unknown. Here, we established a protocol for bioimaging of multiple elements at a cellular level in rice node by laser ablation‐inductively coupled plasma‐mass spectrometry (LA‐ICP‐MS), and compared the mineral distribution profile between wild‐type (WT) rice and mutants. Both relative comparison of mineral distribution normalized by endogenous ¹³C and quantitative analysis using spiked standards combined with soft ablation gave valid results. Overall, macro‐nutrients such as K and Mg were accumulated more in the phloem region, while micro‐nutrients such as Fe and Zn were highly accumulated at the inter‐vascular tissues of the node. In mutants of nodal Zn transporter OsHMA2, Zn localization pattern in the node tissues did not differ from that of WT; however, Zn accumulation in the inter‐vascular tissues was lower in uppermost node I but higher in the third upper node III compared with the WT. In contrast, Si deposition in the mutants of three nodal Si transporters Lsi2, Lsi3 and Lsi6 showed different patterns, which are consistent with the localization of these transporters. This improved LA‐ICP‐MS analysis combined with functional characterization of transporters will provide further insight into mineral element distribution mechanisms in rice and other plant species.     

Resveratrol protects against isoproterenol induced myocardial infarction in rats through VEGF-B/AMPK/eNOS/NO signalling pathway

According to our previous results, resveratrol (RSV, 3, 5, 4-trihydroxystilbene), a naturally polyphenolic phytoalexin, could attenuate myocardial ischemia/reperfusion injury through up-regulation of vascular endothelial growth factor B (VEGF-B) in isolated rat heart or H9c2 cells. However, the molecular mechanism remains unclear. In this study, we investigated the protective effect of RSV on myocardial infarction (MI) in rats and further explored the underlying signal pathway after VEGF-B. Rats received RSV or normal saline by intragastric administration for 7 consecutive days and followed by subcutaneously isoproterenol (ISO) or normal saline injections for another 2 days. We found that RSV pretreatment prevented the unfavourable changes in HW/BW, HW/TL, infarct size, and cell apoptosis in ISO-treated rats. Moreover, superoxide and malondialdehyde (MDA) production were significantly reduced and superoxide dismutase (SOD) was increased by RSV in ISO-treated rats. Furthermore, it showed that RSV pretreatment increased VEGF-B, p-eNOS and p-AMPK expression, and NO production in ISO-treated rats. Using Neonatal Rat Ventricular Myocytes (NRVM), we found that VEGF-B siRNA could abolish the cardio-protective effect of RSV. The enhanced ratios of eNOS phosphorylation to eNOS expression induced by RSV were markedly reversed by VEGF-B siRNA in NRVM also. Meantime, we found that the effect of VEGF-B knock-down on eNOS activation was rescued by AMPK activator AICAR. L-NAME, a NOS inhibitor, could inhibit RSV enhanced eNOS phosphorylation but had no effect on VEGF-B expression in NRVM or in rats. Collectively, our results indicate that RSV exerts cardio-protection from ISO-induced myocardial infarction through VEGF-B/AMPK/eNOS/NO signalling pathway.     

Ablation-index guided versus conventional contact-force guided ablation in pulmonary vein isolation – Systematic review and meta-analysis

BackgroundContact-force sensing catheter is widely used for catheter ablation, however, it did not take account of radiofrequency power. Ablation index (AI) is a novel marker incorporating contact force-time-power, was shown to be reliable in predicting lesion size and depth for radiofrequency delivery. We aimed to assess the latest evidence on ablation index guided procedure versus conventional ablation procedure.MethodsWe performed a comprehensive search on topic that assesses ablation index guided procedure versus conventional procedures from inception up until February 2019 through PubMed, EuropePMC, EBSCOhost, Cochrane Central Database, and ClinicalTrials.gov.ResultsA total of 1727 subjects from five studies were included. 12 months’ incidence of AF/AT/AFL was lower in ablation index guided with an OR of 0.35 [0.17, 0.73], p = 0.005; I² 58%. Upon sensitivity analysis by removing a study, heterogeneity decreased to 0% with OR of 0.26 [0.15, 0.46], p < 0.001. First-pass isolation has a pooled OR of 11.29 [4.68, 27.20], p < 0.001; I² 58%. Pooled OR for acute pulmonary vein reconnection was 0.43 [0.29, 0.64], p < 0.001; I² 46%. AI group has a shorter fluoroscopy time of MD -1.62 [-2.62, ?0.62] minutes, p = 0.001; I² 51% and total ablation time MD -9.96 [-17.16, ?2.76] minutes, p < 0.001; I² 95%. Total procedural time and complication rate were similar.ConclusionAblation index guided procedure resulted in a significantly lower incidence of AF/AT/AFL, shorter fluoroscopy time, and total ablation time. First-pass isolation was higher in AI group and acute PVR was lower in AI group. Ablation-index guided procedure has a similar safety profile to conventional ablation.     

Meltrin beta expressed in cardiac neural crest cells is required for ventricular septum formation of the heart

The heart is divided into four chambers by membranous septa and valves. Although evidence suggests that formation of the membranous septa requires migration of neural crest cells into the developing heart, the functional significance of these neural crest cells in the development of the endocardial cushion, an embryonic tissue that gives rise to the membranous appendages, is largely unknown. Mice defective in the protease region of Meltrin beta/ADAM19 show ventricular septal defects and defects in valve formation. In this study, by expressing Meltrin beta in either endothelial or neural crest cell lineages, we showed that Meltrin beta expressed in neural crest cells but not in endothelial cells was required for formation of the ventricular septum and valves. Although Meltrin beta-deficient neural crest cells migrated into the heart normally, they could not properly fuse the right and left ridges of the cushion tissues in the proximal outflow tract (OT), and this led to defects in the assembly of the OT and AV cushions forming the ventricular septum. These results genetically demonstrated a critical role of cardiac neural crest cells expressing Meltrin beta in triggering fusion of the proximal OT cushions and in formation of the ventricular septum.     

Morbidity and mortality risk associated with an overweight BMI in older men and women

Background: There is controversy as to whether older adults with a BMI in the overweight range (25 to 29.9 kg/m²) are at increased health risk and whether they should be encouraged to lose weight. The purpose of this study was to determine whether older adults with a BMI in the overweight range are at increased morbidity and mortality risk. Methods: Participants consisted of 4968 older (≥65 years) men and women from the Cardiovascular Health Study limited access dataset. Based on BMI (kg/m²), participants were grouped into normal‐weight (20 to 24.9 kg/m²), overweight (25 to 29.9 kg/m²), and obese (≥30 kg/m²) categories. Participants were followed for up to 9 years to determine if they developed 10 weight‐related health outcomes that are pertinent to older adults. Cox proportional hazards models were used to estimate the hazards ratios of morbidity and mortality after adjusting for age, sex, income, smoking, and physical activity. Results: Compared with the normal‐weight group, the risks of myocardial infarction, stroke, sleep apnea, urinary incontinence, cancer, and osteoporosis were not different in the overweight group (p > 0.05). The risks for arthritis and physical disability were modestly increased in the overweight group (p < 0.05), whereas the risk for type 2 diabetes was increased by 78% in the overweight group (p < 0.01). After adjusting for all relevant covariates, all‐cause mortality risk was 11% lower in the overweight group (p < 0.05). Conclusions: A BMI in the overweight range was associated with some modest disease risks but a slightly lower overall mortality rate. These findings suggest that a BMI cut‐off point of 25 kg/m² may be overly restrictive for the elderly.     

基于电子病历的急性ST段抬高型心肌梗死临床路径与决策辅助系统

目的:研究在结构化电子病历上实现计算机化的急性ST段抬高型心肌梗死临床路径,进一步评价该方法的试用结果,为辅助临床医生治疗决策、规范治疗行为,并借此提高医疗质量,合理控制医疗费用提供有效的手段。方法:选取最新的、具有权威性的关于急性ST段抬高型心肌梗死诊治指南作为制定治疗决策方案及编写临床路径的依据;通过程序设计将临床路径编写入医学知识库系统,并将医学知识库系统与结构化电子病历进行无缝连接;将20例无严重并发症的急性ST段抬高型心肌梗死病人均分为两组,其中观察组推行计算机化临床路径,在患者住院天数、住院费用、患者及家属满意度以及医生对该系统的评价方面与对照组进行比较。结果:观察组患者平均住院天数及平均住院费用明显低于对照组(p＜0．000);患者及家属满意度普遍提高(p＜0．05);该系统得到所有被调查医生的认可。结论:运用计算机化临床路径管理无严重并发症的急性ST段抬高型心肌梗死患者能在维持甚至提高医疗质量的前提下,减少患者平均住院天数、平均住院费用,提高患者及家属对医疗行为的满意度,增强医生对治疗指南的顺从性。     

Propofol-mediated cardioprotection dependent of microRNA-451/HMGB1 against myocardial ischemia-reperfusion injury

Administration of propofol at the time of reperfusion has shown to protect the heart from ischemia and reperfusion (I/R) injury. The aim of the present study was to investigate the molecular mechanism underling the cardioprotective effect of propofol against myocardial I/R injury (MIRI) in vivo and in vitro. Rat heart I/R injury was induced by ligation of the left anterior descending (LAD) artery for 30 min followed by 2-hr reperfusion. Propofol pretreatment (0.01 mg/g) was performed 10 min before reperfusion. In vitro MIRI was investigated in cultured cardiomyocytes H9C2 following hypoxia/reoxygenation (H/R) injuries. Propofol pretreatment in vitro was achieved in the medium supplemented with 25 μmol/L propofol before H/R injuries. Propofol pretreatment significantly increased miRNA-451 expression, decreased HMGB1 expression, reduced infarct size, and I/R-induced cardiomyocyte apoptosis in rat hearts undergoing I/R injuries. Knockdown of miRNA-451 48 hr before I/R injury was found to increase HMGB1 expression, infarct size, and I/R-induced cardiomyocyte apoptosis in rat hearts in the presence of propofol pretreatment. These in vivo findings were reproduced in vivo that knockdown of miRNA-451 48 hr before H/R injuries increased HMGB1 expression and H/R-induced apoptosis in cultured H9C2 supplemented with propofol. In addition, luciferase activity assays and gain-of-function studies found that propofol could decrease HMGB1, the target of miRNA-541. Taken together our findings provide a first demonstration that propofol-mediated cardioprotection against MIRI is dependent of microRNA-451/HMGB1. The study provides a novel target to prevent I/R injury during propofol anesthesia.