MRPs

MRP
  • 文章类型: Journal Article
    Mitoribosomes对于生物能源的生产至关重要。人有丝分裂体小亚基(MRPS)家族,负责编码线粒体核糖体小亚基,在线粒体内积极参与蛋白质合成。有趣的是,MRPS家族基因似乎在癌症中起作用。采用多步骤过程建立与MRPS基因相关的风险模型,旨在描绘透明细胞肾细胞癌(ccRCC)的免疫和药物基因组格局。计算个体患者的MRPScore,以评估他们对各种治疗方式的反应性以及对不同治疗靶标和药物的敏感性。虽然MRPS家族基因作为癌基因与各种癌症有关,我们的发现揭示了MRPS基因在ccRCC中的抑癌作用。利用MRPS相关风险模型,我们观察到其在预测ccRCC患者生存结局方面具有出色的预后能力。值得注意的是,具有高MRPS相关评分(MRPScore)的亚组显示较差的预后,但对免疫疗法的反应更强烈.通过对2183个药物靶标和1646个化合物的计算机筛选,我们确定了两个目标(RRM2和OPRD1)和八个试剂(AZ960,卡莫司汀,lasalocid,SGI-1776,AZD8055_1059,BPD.00008900_1998,MK.8776_2046和XAV939_1268)对高MRPScore患者具有潜在的治疗意义。我们的研究代表了在提出分子分类方面的开创性努力,诊断,和治疗策略可以根据MRPScore制定。的确,高MRPScore谱似乎会增加肿瘤进展和死亡的风险,可能通过其对免疫调节的影响。这表明MRPS相关风险模型有望作为预后预测因子,并可能为个性化治疗策略提供新的见解。
    Mitoribosomes are essential for the production of biological energy. The Human Mitoribosomal Small Subunit unit (MRPS) family, responsible for encoding mitochondrial ribosomal small subunits, is actively engaged in protein synthesis within the mitochondria. Intriguingly, MRPS family genes appear to play a role in cancer. A multistep process was employed to establish a risk model associated with MRPS genes, aiming to delineate the immune and pharmacogenomic landscapes in clear cell renal cell carcinoma (ccRCC). MRPScores were computed for individual patients to assess their responsiveness to various treatment modalities and their susceptibility to different therapeutic targets and drugs. While MRPS family genes have been implicated in various cancers as oncogenes, our findings reveal a contrasting tumor suppressor role for MRPS genes in ccRCC. Utilizing an MRPS-related risk model, we observed its excellent prognostic capability in predicting survival outcomes for ccRCC patients. Remarkably, the subgroup with high MRPS-related scores (MRPScore) displayed poorer prognosis but exhibited a more robust response to immunotherapy. Through in silico screening of 2183 drug targets and 1646 compounds, we identified two targets (RRM2 and OPRD1) and eight agents (AZ960, carmustine, lasalocid, SGI-1776, AZD8055_1059, BPD.00008900_1998, MK.8776_2046, and XAV939_1268) with potential therapeutic implications for high-MRPScore patients. Our study represents the pioneering effort in proposing that molecular classification, diagnosis, and treatment strategies can be formulated based on MRPScores. Indeed, a high MRPScore profile appears to elevate the risk of tumor progression and mortality, potentially through its influence on immune regulation. This suggests that the MRPS-related risk model holds promise as a prognostic predictor and may offer novel insights into personalized therapeutic strategies.
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  • 文章类型: Journal Article
    由于年龄受损的身体系统和同时使用多种药物的倾向,与药物相关的问题(MRP)在虚弱的老年人中很常见。这群人也会屈服于健康的快速恶化。因此,在虚弱的老年人中调查MRP很重要.该研究的目的是评估MRPs的患病率,MRP的类型,在从初级保健中心接受英语教学医院的虚弱老年人中,可能与MRP相关的风险因素和恶化。
    样本中包括体弱的老年人,65岁及以上,从初级保健入院。从医院的电子病历系统检索数据,匿名化,并审查了MRP。入院时回顾性鉴定的MRP用WHO-ICD10,2016(世界卫生组织-国际疾病分类第10版,2016)编码。使用SPSS第25版对数据进行描述性和推断性统计。主要结果是虚弱的老年患者的MRPs患病率。次要结果是表现为跌倒的恶化的关联,谵妄,或存在MRPs的NEW≥3。
    在符合纳入标准的507名虚弱的老年人(罗克伍德量表≥4名)中,262例(51.8%)患者有MRPs,244例(48.2%)无MRPs。样本整体的中位年龄为85岁(IQR=80-89)。MRPs的患病率为33.28%。MRP的类型为药物不良反应(ADR-20%),不合规(9.1%),意外中毒(3.3%)和不适当的多重用药(0.8%)。在逻辑回归中,潜在不当药物(PIM),社会支持,合并症数量和冬季是MRP的重要预测因素。MRP患者谵妄恶化的风险是无MRP患者的两倍,RR2.613(95%CI,1.049至6.510)。
    可以降低体弱老年人的MRP和与MRP相关的恶化风险。这是因为可以修改与MRP相关联的因素。
    UNASSIGNED: Medicines related problems (MRPs) can be common in frail older people due to age-compromised body systems and a propensity to be on multiple drugs concurrently. This group of people can also succumb to a rapid deterioration in health. Thus, it is important to investigate MRPs in frail older people. The objectives of the study were to evaluate prevalence of MRPs, types of MRPs, risk factors and deterioration that can be associated with MRPs in frail older people admitted to an English teaching hospital from primary care.
    UNASSIGNED: Included in the sample were frail older adults, aged 65 years and over, admitted from primary care. Data was retrieved from the hospital\'s electronic patient record system, anonymised, and reviewed for MRPs. MRPs which were retrospectively identified at admission were coded with the WHO-ICD10,2016 (World Health Organisation-International Classification of Diseases version 10, 2016). Descriptive and inferential statistics were performed on the data using SPSS Version 25. Primary outcome was the prevalence of MRPs in frail older patients. Secondary outcome was the association of deterioration indicated as fall, delirium, or NEWs ≥3 with presence of MRPs.
    UNASSIGNED: Among the 507 frail older people (≥4 on Rockwood scale) that met criteria for inclusion, 262 (51.8%) were patients with MRPs and 244 (48.2%) without. The Median age of sample as a whole was 85 years (IQR = 80-89). Prevalence of MRPs was 33.28%. Types of MRPs were adverse drug reaction (ADR-20%), non-compliance (9.1%), unintentional poisoning (3.3%) and inappropriate polypharmacy (0.8%). In logistic regression, potentially inappropriate medicines (PIM), social support, number of comorbidities and winter were significant predictors of MRPs. Risk of deteriorating with delirium was two times higher in patients with MRPs than in patients without MRPs, RR 2.613 (95% CI, 1.049 to 6.510).
    UNASSIGNED: MRPs and risks of deterioration associated with MRPs in frail older people can be reduced. This is because factors associated with MRPs can be modified.
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  • 文章类型: Journal Article
    然而,煎炸(PF)是一种常见的热处理,使用与未涂覆的铁锅直接接触,PF后肉类氧化的数据有限。PF之后,形成了地壳,在这项研究中,我们的目的是评估这种外壳的潜在抗氧化和抗脂质过氧化能力。使用PF或微波对磨碎的牛肉和火鸡肉进行热处理。使用丙二醛积累评估脂质过氧化。与微波加热的肉相比,PF肉产生的脂质过氧化水平较低。与Teflon锅加热相比,铁PF降低了脂质过氧化。外壳显着降低脂质过氧化并具有研磨反应产物(MRP),强大的还原能力,碘去除能力,和一些铁螯合能力。我们证明了外壳大大降低了各种系统中的脂质过氧化水平,并且可以用作新型的半天然抗氧化剂成分,这可能导致延长保质期并保护各种食品。
    Pan Fry (PF) is a common heating treatment however, there is limited data on meat oxidation after PF using direct contact with an uncoated iron pan. After PF, a crust is formed, and in this study, we aim to evaluate the potential anti-oxidation and anti-lipid peroxidation capacity of such crust. Ground beef and turkey meat were heat treated using PF or microwave. Lipid peroxidation was evaluated using malondialdehyde accumulation. PF meat generated lower lipid peroxidation levels versus microwave-heated meat. Iron PF has decreased lipid peroxidation versus Teflon pan heating. The crust significantly lowered lipid peroxidation and possessed millard reaction products (MRPs), strong reducing abilities, iodine removal capacity, and some iron chelation capacity. We demonstrated that the crust substantially decreases lipid peroxidation levels in various systems and can be used as a novel seminatural antioxidant ingredient, which may lead to extended shelf life and protects various food products.
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  • 文章类型: Journal Article
    近年来,通过正向遗传方法在理解黄酮类化合物的生物合成途径和调控方面取得了重大进展。然而,关于负责类黄酮运输的运输框架的功能表征和基本过程的知识仍然存在明显差距。这方面需要进一步调查和澄清,以达到全面的理解。目前,总共有四个与类黄酮相关的运输模型,即谷胱甘肽S-转移酶(GST),多种药物和有毒化合物挤出(MATE),多药耐药相关蛋白(MRP),和胆红素转移酶同源物(BTL)。已经对与这些转运模型相关的蛋白质和基因进行了广泛的研究。然而,尽管做出了这些努力,仍然存在许多挑战,未来还有很多需要探索的地方。对这些运输模型的潜在机制有更深入的了解,对于代谢工程等各个领域都具有巨大的潜力。生物技术方法,植物保护,和人类健康。因此,这篇综述旨在全面概述黄酮类化合物转运机制的最新进展。通过这样做,我们的目标是为类黄酮的动态贩运描绘一幅清晰连贯的画面。
    In recent years, significant progress has been made in understanding the biosynthetic pathway and regulation of flavonoids through forward genetic approaches. However, there remains a notable gap in knowledge regarding the functional characterization and underlying processes of the transport framework responsible for flavonoid transport. This aspect requires further investigation and clarification to achieve a comprehensive understanding. Presently, there are a total of four proposed transport models associated with flavonoids, namely glutathione S-transferase (GST), multidrug and toxic compound extrusion (MATE), multidrug resistance-associated protein (MRPs), and bilitranslocase-homolog (BTL). Extensive research has been conducted on the proteins and genes related to these transport models. However, despite these efforts, numerous challenges still exist, leaving much to be explored in the future. Gaining a deeper understanding of the mechanisms underlying these transport models holds immense potential for various fields such as metabolic engineering, biotechnological approaches, plant protection, and human health. Therefore, this review aims to provide a comprehensive overview of recent advancements in the understanding of flavonoid transport mechanisms. By doing so, we aim to paint a clear and coherent picture of the dynamic trafficking of flavonoids.
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  • 文章类型: Journal Article
    核糖体是最复杂和最古老的细胞大分子组件之一,在所有活细胞的蛋白质生物合成中起着核心作用。其将信使RNA编码的遗传信息翻译成蛋白质分子的功能也延伸到真核细胞中的亚细胞区室,例如原生质体,叶绿体,和线粒体.线粒体的起源主要归因于α-变形杆菌和原始(古细菌)真核细胞之间的早期内共生事件。线粒体获取的时间表,主机的性质,它们的多样化已经被研究得非常详细,并且随着更多的基因组和结构数据的出现而不断被修改。高分辨率低温EM结构测定的最新进展提供了来自各种物种的线粒体核糖体(线粒体)的结构细节,揭示了他们之间前所未有的多样化。这些结构为线粒体结构和功能的进化提供了新的见解。这里,在真核进化树的背景下,我们对现有的有丝分裂体结构进行了简要概述,显示了它们从最后一个共同祖先的多样化。
    The ribosome is among the most complex and ancient cellular macromolecular assemblies that plays a central role in protein biosynthesis in all living cells. Its function of translation of genetic information encoded in messenger RNA into protein molecules also extends to subcellular compartments in eukaryotic cells such as apicoplasts, chloroplasts, and mitochondria. The origin of mitochondria is primarily attributed to an early endosymbiotic event between an alpha-proteobacterium and a primitive (archaeal) eukaryotic cell. The timeline of mitochondrial acquisition, the nature of the host, and their diversification have been studied in great detail and are continually being revised as more genomic and structural data emerge. Recent advancements in high-resolution cryo-EM structure determination have provided architectural details of mitochondrial ribosomes (mitoribosomes) from various species, revealing unprecedented diversifications among them. These structures provide novel insights into the evolution of mitoribosomal structure and function. Here, we present a brief overview of the existing mitoribosomal structures in the context of the eukaryotic evolution tree showing their diversification from their last common ancestor.
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  • 文章类型: Journal Article
    购买最低限度加热和即食食品的新兴消费者趋势可能导致加工方法不能有效减少致病人群。粗美拉德反应产物(MRP)是天然产生的化合物,其已显示出对病原体的抗微生物作用。从还原糖(果糖(Fru),葡萄糖(Glc),使用420nm(Ab420)的吸光度测量核糖(Rib)或木糖(Xyl)与赖氨酸和类黑素的等效性。通过检查滞后期的长度和最大生长速率来测量每个MRP的相对抗微生物活性。发现MRP显着缩短了滞后期并降低了鼠伤寒沙门氏菌的最大生长速率(p<0.05)。确定葡萄糖-赖氨酸MRP(GLMRP)具有最高的相对黑素(在Ab420时为1.690±0.048),并在37°C和pH7.0下测量其对抗鼠伤寒沙门氏菌种群的功效,并在木糖赖氨酸脱氧胆酸盐(XLD)琼脂上进行评估。在接种后8和24小时,GLMRP显著减少鼠伤寒沙门氏菌种群>1logCFU/mL(p<0.05)。GLMRP还在热应激条件(55°C)下与最佳(37°C)相比,进一步显着降低了鼠伤寒沙门氏菌种群〜1logCFU/mL(p<0.05)。总的来说,GLMRP在37°C和55°C下证明了对鼠伤寒沙门氏菌的有效抗菌活性。
    An emerging consumer trend to purchase minimally heated and ready-to-eat food products may result in processing methods that do not effectively reduce pathogenic populations. Crude Maillard reaction products (MRPs) are naturally generated compounds that have been shown to display antimicrobial effects against pathogens. Crude MRPs were generated from reducing sugars (fructose (Fru), glucose (Glc), ribose (Rib) or xylose (Xyl)) with lysine and the melanoidin equivalence was measured using an absorbance of 420 nm (Ab420). The relative antimicrobial activity of each MRP was measured by examining both the length of lag phase and maximum growth rate. MRPs were found to significantly shorten the lag phase and decrease the maximum growth rate of S. Typhimurium (p < 0.05). Glucose-lysine MRP (GL MRP) was determined to have the highest relative melanoidin (1.690 ± 0.048 at Ab420) and its efficacy against S. Typhimurium populations was measured at 37 °C and at pH 7.0 and estimated on xylose lysine deoxycholate (XLD) agar. GL MRP significantly reduced S. Typhimurium populations by >1 log CFU/mL at 8 and 24 h after inoculation (p < 0.05). GL MRPs also further decreased S. Typhimurium populations significantly under thermal stress condition (55 °C) compared to optimal (37 °C) by ~1 log CFU/mL (p < 0.05). Overall, GL MRP demonstrated effective antimicrobial activity against S. Typhimurium at 37 °C and 55 °C.
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  • 文章类型: Journal Article
    在废活性污泥(WAS)的热水解预处理(THP)过程中产生的耐火美拉德反应产物(MRP)可能会对下游厌氧消化(AD)和脱氮过程的性能产生负面影响。在较低温度下操作THP可以减轻MRP的产生并改善WAS的生物降解性,而WAS的溶解减少。这项研究旨在开发一种减少WAS的难降解MRP而不损害溶解的方法。将Fe3+引入THP工艺(165℃,30分钟)以减轻美拉德反应。Fe3+对WAS增溶的影响,减少难处理残差,累积甲烷产量,并对微生物群落迁移进行了研究。结果证实,添加10mg-Fe/LFeCl3后,WAS的增溶作用得到改善,难降解残留物减少。研究了MRP缓解机制,主要归因于Fe3触发的Fenton样反应。甲烷产量提高了10.4±0.8%,这归因于THP液体的生物降解性提高,以及与蛋白质降解和产甲烷相关的微生物群落的富集。这项工作提供了一个简单的,经济,和安全策略,以减少从THP-AD系统排放的难降解残留物,并提高甲烷产量以回收更多的能量。
    Refractory Maillard reaction products (MRPs) produced during thermal hydrolysis pretreatment (THP) of waste activated sludge (WAS) may negatively impact the performance of downstream anaerobic digestion (AD) and nitrogen removal processes. Operating THP at lower temperature can mitigate the production of MRPs and improve biodegradability of WAS, while solubilization of WAS is reduced. This study intends to develop a method to reduce the refractory MRPs of WAS without compromising on the solubilization. Fe3+ was introduced into THP process (165 °C, 30 min) to mitigate Maillard reaction. Effects of Fe3+ on solubilization of WAS, reduction of refractory residuals, accumulative methane production, and microbial community shift were studied. Results confirm that solubilization of WAS was improved and refractory residuals were reduced with the amendment of 10 mg-Fe/L FeCl3. MRPs mitigation mechanisms were investigated and mainly attributed to Fe3+-triggered Fenton-like reactions. Methane production was enhanced by 10.4 ± 0.8% and attributed to the improved biodegradability of THP liquor, as well as to the enrichment of protein degradation and methane production related microbial community. This work provides a simple, economical, and safe strategy to reduce refractory residuals discharged from THP-AD system and to enhance methane production for more energy recovery.
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  • 文章类型: Journal Article
    In this study, oils extracted from nigella seeds (NS) subjected to microwave roasting at 180, 360, 540 and 720 W for 5 and 10 min were evaluated for quality and stability characteristics. The impact of microwave powers on oil yield, pigment content, Maillard reaction products (MRPs), radical scavenging activity (RSA), color, viscosity, total phenolic content (TPC), oxidative stability index (OSI) and fatty acid composition (FAC) of oil was studied. TPC, RSA, OSI, MRPs, viscosity, chlorophyll and carotenoid contents were higher in oil of NS heated at 720 W for 10 min while maximum oil yield and low acid value was observed for NS heated at 540 W for 10 min. FAC was slightly influenced by microwave roasting and FTIR spectra exhibited a minor difference in intensities of peaks at 3009, 2925, 2854, 1745 and 1161 cm-1. The results of the study indicated that microwave roasting improves NS oil quality characteristics.
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  • 文章类型: Systematic Review
    随着年龄的增长,由于身体系统的变化,它们越来越容易受到药物的不利影响。这些可能导致药物相关问题(MRP)和随之而来的健康下降或恶化。
    要识别MRP,与这些MRP相关的恶化指标,以及文献中的预防性干预措施。
    关于老年人初级保健中的MRP的初步研究的系统评价。
    2001年至2018年4月发表的相关研究来自Medline(通过PubMed),CINAHL,Embase,心理信息,帕斯卡尔,Scopus,科克伦图书馆,科学直接,还有Zetoc.瀑布,谵妄,压疮,住院治疗,使用卫生服务和死亡是公认的恶化指标.使用DownandBlack工具评估纳入研究的方法学质量。
    从数据库中检索到1858篇文章。在这些中,21篇全文符合审查的纳入标准。MRP鉴定为用药错误,潜在的不适当的药物,药物不良反应和不依从性。这些与恶化的指标有关。涉及医生的干预措施,药剂师和患者在计划和实施中,在停止MRP方面获益.
    本系统综述总结了MRP和相关的恶化指标。适当的干预措施似乎对某些MRP及其后果有效。必须进行进一步的研究,以探索本系统综述中提出的恶化。
    UNASSIGNED: As people age, they become increasingly vulnerable to the untoward effects of medicines due to changes in body systems. These may result in medicines related problems (MRPs) and consequent decline or deterioration in health.
    UNASSIGNED: To identify MRPs, indicators of deterioration associated with these MRPs, and preventative interventions from the literature.
    UNASSIGNED: Systematic review of primary studies on MRPs originating in Primary Care in older people.
    UNASSIGNED: Relevant studies published between 2001 and April 2018 were obtained from Medline (via PubMed), CINAHL, Embase, Psych Info, PASCAL, Scopus, Cochrane Library, Science Direct, and Zetoc. Falls, delirium, pressure ulcer, hospitalization, use of health services and death were agreed indicators of deterioration. The methodological quality of included studies was assessed using the Down and Black tool.
    UNASSIGNED: There were 1858 articles retrieved from the data bases. Out of these, 21 full text articles met inclusion criteria for the review. MRPs identified were medication error, potentially inappropriate medicines, adverse drug reaction and non-adherence. These were associated with indicators of deterioration. Interventions that involved doctors, pharmacists and patients in planning and implementation yielded benefits in halting MRPs.
    UNASSIGNED: This Systematic review summarizes MRPs and associated indicators of deterioration. Appropriate interventions appeared to be effective against certain MRPs and their consequences. Further studies to explore deterioration presented in this systematic review is imperative.
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  • 文章类型: Journal Article
    血液透析(HD)患者有复杂的疾病状态,使他们面临更高的药物相关问题的风险,用药差异,和不坚持。这项研究的目的是通过评估HD患者药物和解的功效并评估对单一医疗保健系统的潜在影响来评估临床药师在单一HD机构中的影响。
    回顾性研究。
    格林菲尔德卫生系统,亨利·福特健康系统的全资子公司,在密歇根州东南部经营14个高清设施。西馆设施位于底特律,MI.在2017年8月至2018年10月期间,纳入研究的终末期肾脏疾病患者至少与临床药师或药学实习生接触了4次。
    临床药剂师对HD患者进行了药物和解和药物审查,以评估药物相关问题并确定护理方面的差距。药剂师的干预是通过合作实践协议预先指定的。
    评估临床药剂师在HD机构中的影响,通过评估HD患者的药物和解的功效,并通过估计的成本避免评估对该卫生系统的潜在影响。
    描述性统计用于收集与药物相关的问题,并根据改进的Hepler-Strand方法进行分类。
    有1,403个与药物有关的问题,每个患者平均有8.96个药物相关问题。坚持是最常见的药物相关问题(31%)。抗高血压药物是药剂师干预的最常见的药物类别(37%),其次是维生素D类似物和拟钙剂(29%)。预计总共节省了447355美元。
    对观察数据和描述性统计进行回顾性分析,可能存在残留偏差和混淆。
    HD机构的药剂师通过药物管理对HD患者产生积极影响,从而节省成本。
    UNASSIGNED: Hemodialysis (HD) patients have complicated disease states, placing them at higher risk for medication-related problems, medication discrepancies, and nonadherence. The objective of this study is to evaluate the impact of a clinical pharmacist in a single HD facility by assessing the efficacy of medication reconciliation in HD patients and evaluating the potential impact on a single health care system.
    UNASSIGNED: Retrospective study.
    UNASSIGNED: Greenfield Health Systems, a wholly owned subsidiary of Henry Ford Health System, operates 14 HD facilities throughout Southeast Michigan. The West Pavilion facility is located in Detroit, MI. Patients with end-stage kidney disease included in the study had a minimum of 4 encounters with the clinical pharmacist or pharmacy interns between August 2017 and October 2018.
    UNASSIGNED: A clinical pharmacist performed medication reconciliation and medication reviews with HD patients to assess medication-related problems and identify gaps in care. Interventions made by the pharmacist were prespecified through a collaborative practice agreement.
    UNASSIGNED: To evaluate the impact of a clinical pharmacist in an HD facility by assessing the efficacy of medication reconciliation in HD patients and evaluating the potential impact on this health system through an estimated cost avoidance.
    UNASSIGNED: Descriptive statistics were used to collect medication-related problems and classified based on a modified Hepler-Strand approach.
    UNASSIGNED: There were 1,403 medication-related problems, with an average of 8.96 medication-related problems per patient. Adherence was the most common medication-related problem (31%). Antihypertensive medication was the most common drug class in which the pharmacist intervened (37%), followed by vitamin D analogues and calcimimetics (29%). A projected total of US $447,355 was saved.
    UNASSIGNED: Retrospective analysis of observational data and descriptive statistics with the potential for residual bias and confounding.
    UNASSIGNED: Pharmacists in HD facilities have a positive influence on HD patients through medication management that results in cost savings.
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