Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

防范魔音入耳 关爱听力健康

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衰减伪影对冠心病患者门控心肌灌注显像图像质量及灌注结果的影响

目的探讨衰减伪影对冠心病患者门控心肌灌注显像(GMPI)图像质量及灌注结果的影响。资料与方法回顾性分析2020年3月—2021年3月在郑州大学第一附属医院核医学科经冠状动脉造影证实且于造影前后1周行GMPI的99例冠心病患者的图像,定性及半定量分析衰减校正前后GMPI图像结果,比较衰减校正前后左心室各壁段平均放射性计数及灌注结果的差异,进一步分析衰减校正前后灌注结果不一致部分的受检者的节段性室壁运动及增厚情况。结果与衰减校正前比较,衰减校正后左心室间隔、下后壁及侧壁的平均放射性计数较高(Z=-7.302、-8.014、-3.991,P均<0.001),心尖部较低(Z=-8.021,P<0.001)。其中女性衰减校正后前壁平均放射性计数减低(Z=-2.314,P=0.021)。男性衰减校正前后下后壁放射性计数差值明显高于女性(t=-8.408,P<0.05)。衰减校正后44%(44/99)的左前降支及37%(37/99)的右冠状动脉分支供血区域显像结果发生改变,结合超声心动图及GMPI结果显示其中85%(35/41)的左前降支及81%(29/36)的右冠状动脉分支供血区域室壁运动及室壁增厚率均正常。结论衰减伪影对GMPI的图像质量和灌注结果有较大影响,结合室壁运动和增厚情况等有助于鉴别衰减伪影,提高诊断准确度与特异度。     

Brachytherapy: An emblematic example of extreme hypofractionated regimen

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3 Gy), then ultra (dose/fraction: 5.2 to 6.1 Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20 Gy/fraction), the use of a single fraction of 19 to 23 Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.     

基于信息平台的医院POCT管理改进

以华中科技大学同济医学院附属同济医院为例，探讨医院通过健全POCT管理体系，并借助信息平台改进POCT管理的经验，为其他医院POCT规范化管理提供参考。该医院通过搭建POCT管理平台，实现了设备标准化准入、人员资质统一授权、设备自动化质控和诊疗全流程闭环管理；基于信息平台的POCT管理改进，提升了医护人员的POCT认知度和操作水平，提高了医疗工作效率；实行诊疗全程风险管控，保障了医疗安全。     

Mobile daily diaries to characterize stressors and acute health symptoms in an environmental justice neighborhood

Low-income communities and communities of color face multiple, cumulative environmental and social burdens. Methods development in environmental justice research has largely focused on spatial and quantitative approaches. Less attention has been paid to developing methodologies that help collect information on everyday stressors and quality of life experiences for residents in overburdened communities. Mixed methods approaches can be one way to structure study designs that help consider how residents experience environmental and socioeconomic impacts in a localized community context. In neighborhoods burdened by cumulative stressors, traditional cross-sectional epidemiological research designs can also be challenging, as well as limited or narrow in their application. However, repeat sampling of measures within a vulnerable population can approach a quasi-experimental design and help consider variations within residents in a single neighborhood as well as better parse relationships between exposures and outcomes. Through a community-academic partnership with university partners, local community partners, and a local promotores de salud (community health workers) network, we pilot tested a novel mobile daily diary approach in both English and Spanish in an urban, predominantly immigrant community in South Los Angeles as a potential method to collect information on daily stress, environmental quality, and health status/symptoms. We collected resident responses via a once per day 7-day SMS/text messaging survey. We sought to gather granular data on daily resident experiences of air pollution and environmental hazards. Residents reported acute health symptoms and stressors, with repeat measures demonstrating how residents might rank, categorize, or cope with stressors. We find that residents in environmental justice communities record variation in their daily diary responses and document changes in environmental quality, stressors, and odors. Refining this type of method could enable a more rigorous examination of co-occurrences of environmental quality and acute health symptoms. This approach supports the inclusion of residents in the research process and helps more systematically integrate open-ended environmental health relevant data in environmental justice efforts. Used with measured data such as air monitoring or health measures, mixed methods generated data can help support efforts that aim to alleviate sources of daily stress, alongside efforts to reduce overall pollution burdens. Mobile daily diaries can be one way to capture variable responses to environmental quality, acute health symptoms, and stressors.     

Effects of the Cerebral Aneurysm Treatment Method on Coil Packing Density and Its Relationship with the Ostium Area

PurposeTo test the following hypotheses: (a) balloon or stent assistance increases coil packing density (CPD) in the endovascular treatment of intracranial aneurysms, and (b) CPD correlates to ostium area (OA) and aneurysm volume (AV).Materials and MethodsThis retrospective study included 60 aneurysms (54 ruptured and 6 unruptured) treated with simple coiling (SC) (n = 18), balloon-assisted coiling (BAC) (n = 7), or stent-assisted coiling (SAC) (n = 35) at the authors’ institution between August 2017 and December 2019. AV and OA measurements were obtained from 3-dimensional digital subtraction angiography images using commercial software. Coil sizes were retrieved from patient files, and coil volume (CV) measurements were obtained from https://www.angiocalc.com/. Analysis of covariance, multivariate covariance analysis, and Pearson correlation analyses were performed.ResultsThe median value for AV, CV, CPD, and OA was 63.4 mm³ (range, 5.5–1,771.4 mm³), 23.13 mm³ (range, 2.03–296.95 mm³), 33.29% (range, 13.41%–81.02%), and 10.7 mm² (range, 2.7–49.9 mm²), respectively. Multivariate analysis showed that the CPD values were not significantly different among the treatment groups, although OA significantly differed between the SC and SAC groups (P < .05). Pearson correlations showed that similar to AV, OA was negatively correlated with CPD (r = ?0.321, P < .05).ConclusionsThe CPD value in cerebral aneurysms treated with BAC or SAC did not differ from that in aneurysms treated with SC.     

阿克替苷通过激活血红素加氧酶-1抑制H_(2)O_(2)诱导的视网膜神经节细胞氧化损伤北大核心

目的研究阿克替苷对视网膜神经节细胞(RGC-5)的保护作用及其机制。方法将RGC-5细胞分为对照组、H_(2)O_(2)组、阿克替苷+H_(2)O_(2)组(1μmol·L^(-1)、10μmol·L^(-1)、30μmol·L^(-1)阿克替苷分别预处理细胞2 h),MTT法检测各组细胞活力;后续实验阿克替苷+H_(2)O_(2)组选择阿克替苷30μmol·L^(-1)作为治疗浓度,荧光探针H2DCF-DA检测活性氧(ROS)产生和罗丹明123检测线粒体膜电位,Western blot检测各组细胞中Bcl-2、Bcl-2/Bax、半胱氨酸蛋白酶-3(Caspase-3)蛋白表达。机制研究中首先用不同浓度阿克替苷单独处理RGC-5细胞24 h,Western blot检测血红素加氧酶-1(HO-1)蛋白表达水平,进一步锌原卟啉(ZnPP)预处理RGC-5细胞1 h,而后30μmol·L^(-1)阿克替苷单独预处理后与200μmol·L^(-1)H_(2)O_(2)共孵育24 h,通过MTT法测定细胞活力。结果与对照组相比,H_(2)O_(2)组中细胞活力明显降低(P<0.01)。与H_(2)O_(2)组相比,阿克替苷+H_(2)O_(2)组中10μmol·L^(-1)、30μmol·L^(-1)阿克替苷预处理可显著提高细胞活力(P<0.05、P<0.01)。与对照组相比,H_(2)O_(2)组RGC-5细胞ROS生成明显增加,线料体膜电位显著降低,同时Bcl-2/Bax比值降低和Caspase-3蛋白相对表达量增加(均为P<0.05)。与H_(2)O_(2)组相比,阿克替苷+H_(2)O_(2)组RGC-5细胞ROS生成减少,线粒体膜电位增加,Bcl-2/Bax比值提高,Caspase-3蛋白相对表达量减少(均为P<0.05)。与阿克替苷未处理组相比,阿克替苷剂量依赖性诱导HO-1蛋白的表达,与阿克替苷+H_(2)O_(2)组相比,加入ZnPP后细胞活力降低(P<0.01),说明HO-1抑制剂ZnPP降低了阿克替苷对H_(2)O_(2)损伤的抑制作用。结论阿克替苷能够通过上调HO-1表达抑制H_(2)O_(2)诱导的RGC-5氧化应激损伤。