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.     

Motivational interviewing for maternal Immunizations: Intervention development

Background and ObjectiveVaccine uptake during pregnancy remains low. Our objectives were to describe 1) development and adaptation of a clinician communication training intervention for maternal immunizations and 2) obstetrics and gynecology (ob-gyn) clinician and staff perspectives on the intervention and fit for the prenatal care context.MethodsDesign of the Motivational Interviewing for Maternal Immunizations (MI4MI) intervention was based on similar communication training interventions for pediatric settings and included presumptive initiation of vaccine recommendations (“You’re due for two vaccines today”) combined with motivational interviewing (MI) for hesitant patients. Interviews and focus group discussions were conducted with ob-gyn clinicians and staff in five Colorado clinics including settings with obstetric physicians, certified nurse midwives (CNMs), and clinician-trainees. Participants were asked about adapting training to the ob-gyn setting and their implementation experiences. Feedback was incorporated through iterative changes to training components.ResultsInterview and focus group discussion results from participants before (n = 3), during (n = 11) and after (n = 25) implementation guided intervention development and adaptation. Three virtual, asynchronous training components were created: a video and two interactive modules. This virtual format was favored due to challenges attending group meetings; however, participants noted opportunities to practice skills through role-play were lacking. Training modules were adapted to include common challenging vaccine conversations and live-action videos. Participants liked interactive training components and use of adult learning strategies. Some participants initially resisted the presumptive approach but later found it useful after applying it in their practices. Overall, participants reported that MI4MI training fit well with the prenatal context and recommended more inclusion of non-clinician staff.ConclusionsMI4MI training was viewed as relevant and useful for ob-gyn clinicians and staff. Suggestions included making training more interactive, and including more complex scenarios and non-clinician staff.     

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.     

朝鲜淫羊藿酸性多糖的理化特性及对HepG2细胞脂质堆积的改善作用＊

目的 对比研究朝鲜淫羊藿酸性多糖酯化还原前后的理化特性，并探讨其改善油酸诱导的肝癌HepG2细胞脂质堆积活性的差异。方法 采用高效凝胶渗透色谱法测定朝鲜淫羊藿酸性多糖（EFPA）的均一性和分子量，高效液相色谱法测定EFPA和酯化还原后朝鲜淫羊藿酸性多糖（EFPA-R）的单糖组成；采用油酸（OA）处理HepG2细胞诱导建立脂质蓄积模型，不同浓度EFPA与EFPA-R（10、30、100、300 μg·mL^-1）分别和OA共同作用于细胞24 h，采用CCK-8试剂盒测定细胞存活率，油红O染色观察细胞内脂滴蓄积情况，并采用试剂盒测定细胞内总胆固醇（TC）、甘油三酯（TG）含量。结果 EFPA为成分均一的多糖组分，分子量为125.8 kDa，由甘露糖、葡萄糖、半乳糖、葡萄糖醛酸和阿拉伯糖组成，摩尔比为1.7∶7.4∶1.4∶1.8∶1.0，葡萄糖占比最大，EFPA-R由甘露糖、葡萄糖、半乳糖和阿拉伯糖组成，摩尔比为0.8∶10.6∶2.1∶1.0；在10-300 μg·mL^-1范围内，EFPA和EFPA-R对HepG2细胞的抑制作用较弱，作为给药浓度；与空白组相比，模型组细胞中TC、TG含量显著升高（P < 0.01），细胞内红色脂滴显著增多，与模型组相比，EFPA可显著降低细胞中TC、TG含量（P < 0.01），明显减少细胞内红色脂滴（P < 0.05或P < 0.01），EFPA-R干预后细胞则无明显变化。结论 EFPA可明显改善HepG2细胞脂质堆积情况，且呈现剂量依赖性，而半乳糖醛酸（GalA）的存在可能是其抑制HepG2细胞脂质蓄积的关键因素。     

蒙药绿松石的质量标准研究＊

目的 建立蒙药绿松石的质量标准。方法 收集不同产地绿松石，共10批。观察绿松石样品和粉末的性状并进行理化鉴别；按2020年版《中国药典》（四部）通则方法测定绿松石样品中水分、浸出物含量；采用原子吸收光谱法测定绿松石样品铜元素含量。结果 绿松石为不规则、周围带有黑石的块状物，表面蓝绿色，体重，质硬脆，难砸碎，断面呈贝壳状，蜡样光泽，粉末呈灰绿色，无臭，味淡；理化鉴别结果显示，呈铜盐反应；10批次样品中水分含量为0.41%-3.94%（SD=1.37%），浸出物含量为0.21%-0.81%（SD=0.21%），铜元素含量为3.03%-4.63%（SD=0.63%）。结论 初步拟定绿松石中水分含量不得超多5.0%、浸出物含量不得低于0.10%，铜元素含量应为2.60%-4.84%，制定的标准可用于蒙药材绿松石的质量控制。     

Metastatic stage vs complications at radical nephrectomy with inferior vena cava thrombectomy

BackgroundTo investigate perioperative complication rates at radical nephrectomy (RN) according to inferior vena cava thrombectomy (IVC-T) status and stage (metastatic vs non-metastatic) within kidney cancer patients.Materials and methodsWe ascertained perioperative complication rates within the National Inpatient Sample database (2016–2019). First, log-link linear Generalized Estimating Equation function (GEE) regression models (adjusted for hospital clustering and weighted for discharge disposition) tested complication rates in IVC-T patients, according to metastatic stage. Subsequently, a subgroup analysis relied on RN patients with or without IVC-T. Here, multivariable logistic regression models tested complication rates in RN patients according to IVC-T status, after propensity score matching including metastatic stage.ResultsOf 26,299 RN patients, 461 (2%) patients underwent IVC-T. Of those, 252 (55%) were non-metastatic vs 209 (45%) were metastatic. Rates of acute kidney injury (AKI), transfusion, cardiac, thromboembolic and other medical complications in non-metastatic vs metastatic patients were 40 vs 40%, 25 vs 22%, 21 vs 23%, 19 vs 14% and 38 vs 40%, respectively (all p ≥ 0.2). Metastatic stage in IVC-T patients did not predict differences in complications in log-link linear GEE regression models (all p > 0.1). However, in logistic regression models with propensity score matching, relying on the overall cohort of RN patients, IVC-T status was associated with higher complication rates (all p < 0.001): AKI (Odds ratio [OR]:2.60; 95%-CI [95%-Confidence interval: 1.97–3.44), transfusions (OR:2.40; 95%-CI: 1.72–3.36), cardiac (OR:2.27; 95%-CI: 1.49–3.47), thromboembolic (OR:9.07; 95%-CI: 5.21–16.58) and other medical complications (OR:2.01; 95%-CI: 1.52–2.66).ConclusionsThe current analyses indicate that presence of concomitant IVC-T is associated with higher complication rate at RN. Conversely, metastatic stage has no effect on recorded complication rates.