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.     

Effectiveness and safety of extracorporeal shock wave treatment for low back pain：a systematic review and meta-analysis of RCTs

This meta-analysis was designed to assess the effectiveness and safety of extracorporeal shock wave therapy (ESWT) for patients with low back pain (LBP). Pubmed, Embase, Cochrane's library, PEDro (Physiotherapy Evidence Database), China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched until December 2019 to identify studies assessing the effectiveness and safety of EPSW for LBP. The prime outcome is pain intensity measured by Visual Analog Scale (VAS) or numeric rating scale (NRS). Other outcomes included functional status, quality of life, psychological outcomes measured by Oswestry Disability Index (ODI), as well as the adverse events. Mean differences (MD) were calculated for continuous outcomes, while odd ratios (OR) were calculated for binary outcomes. Revman 5.3 software was used for statistical analysis. Five randomized controlled trials (RCTs) were finally included in this meta-analysis. The pooled mean difference in post-treatment pain scores was −2.37 (P ＜0.0001), indicating that post-treatment pain scores was significantly higher by 2.37 in control group than in ESWT group. At a mean follow-up time of 4–6 weeks, the pooled mean difference in ODI scores was −14.10 (P ＜0.00001), indicating that the pooled mean difference of post-treatment ODI scores was 14.10 higher in control group than in ESWT group. The use of ESWT is effective in alleviating pain and improving the general functional state for patients with LBP. However, more evidence was needed to verify its safety.     

Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

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补充与替代疗法治疗肠易激综合征的研究进展

肠易激综合征是临床常见的功能性胃肠病之一。由于多数患者的症状经过一线药物治疗后仍不能得到较好改善，许多患者为获得更好的治疗效果，转向选择补充与替代疗法进行治疗。然而，由于研究质量和数量的限制，大部分治疗肠易激综合征的补充与替代疗法并未被相关共识和指南所推荐。本文从补充与替代疗法的分类入手，从天然产品、身心治疗、传统医药3个方面就目前国内外常用的补充与替代疗法治疗肠易激综合征的研究进行概述，以期为临床工作者和患者更好地了解和应用提供帮助。