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.     

脑出血继发损伤中沉默信息调节因子2的表达和炎症反应*

目的：探讨脑出血对酵母沉默信息调节因子2（Sirt2）和炎症的影响。方法：将胶原酶Ⅳ注入SD大鼠右侧 纹状体中建立脑出血模型，通过免疫印迹和ELISA 等方法测定大鼠脑出血后48 h 的Sirt2 的表达及炎症变化。利 用Hemin 诱导PC12 细胞损伤模拟体外脑出血模型，并检测Sirt2 及炎症变化；采用短发夹RNA（shRNA）-Sirt2 沉 默Sirt2 在PC12 细胞中的表达及对炎症的影响。结果：手术后48 h 脑出血行为学评分最低。脑出血组Sirt2 的表达 显著高于假手术组。脑出血组IL-6、IL-1β 表达显著升高。结论：脑出血可以促进Sirt2 的表达和炎症反应，降低 Sirt2 的表达可减缓炎症反应。 关键词 脑出血；沉默信息调节     

Glycaemic control for patients with severe acute brain injury: Protocol for a systematic review

Background

Hyperglycaemia is common in patients with acute brain injury admitted to an intensive care unit (ICU). Many studies have found associations between development of hyperglycaemia and increased mortality in hospitalised patients. However, the optimal target for blood glucose control is unknown. We want to conduct a systematic review with meta-analysis and trial sequential analysis to explore the beneficial and harmful effects of restrictive versus liberal glucose control on patient outcomes in adults with severe acute brain injury.

Methods

We will systematically search medical databases including CENTRAL, Embase, MEDLINE and trial registries. We will search the following websites for ongoing or unpublished trials: http://www.controlled-trials.com/ , http://www.clinicaltrials.gov/ , www.eudraCT.com , http://centerwatch.com/ , The Cochrane Library's CENTRAL, PubMed, EMBASE, Science Citation Index Expanded and CINAHL. Two authors will independently review and select trials and extract data. We will include randomised trials comparing levels of glucose control in our analyses and observational studies will be included to address potential harms. The primary outcomes are defined as all-cause mortality, functional outcome and health-related quality of life. Secondary outcomes include serious adverse events including hypoglycaemia, length of ICU stay and duration of mechanical ventilation, and explorative outcomes including intracranial pressure and infection. Trial Sequential Analysis will be used to investigate the risk of type I error due to repetitive testing and to further explore imprecision. Quality of trials will be evaluated using the Cochrane Risk of Bias tool, and quality of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

Discussion

The results of the systematic review will be disseminated through peer-reviewed publication. With the review, we hope to inform future randomised clinical trials and improve clinical practice.     

Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1

Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose‐starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m‐chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy.     

The apex angle of the rocker sole affects the posture and gait stability of healthy individuals

BackgroundRocker sole (RS) shoes have been linked to impaired postural control. However, which features of RS design affect balance is unclear.Research questionWhich RS design features affect standing balance and gait stability?MethodsThis study utilized an intervention and cross-over design. Twenty healthy young adults (10 males and 10 females) participated in this study. Standing balance and gait stability were measured using a single force platform and three-dimensional motion analysis system, respectively. The experimental conditions included the control shoe and five RS shoes in the combination of apex position (%) and apex angle (degree) for RS50-95, RS60-95, RS70-95, RS60-70, and RS60-110. The main outcome measures were the area surrounding the maximal rectangular amplitude, mean path length, average displacement of the center of pressure along the lateral and anterior/posterior directions, and maximal center of pressure excursion as the standing balance and lateral margin of stability as the gait stability. Statistical analyses were conducted using a two-way split-plot analysis of variance with repeated measures (with RS design as the within-subject factor and sex as the between-subject factor) and the Bonferroni post hoc test (α = .05).ResultsRegarding the mean path length, RS60-70 was significantly longer than the control shoe, and it showed a significantly increased lateral margin of stability. Thus, RS60-70 was shown to affect standing balance, limit of stability, and gait stability of the frontal plane during gait.SignificanceThese results suggest that the apex angle of the RS design feature affects standing balance and gait stability, and RS60-70 is detrimental to stability. Therefore, when RS with a small apex angle is prescribed, it is necessary to consider the patient’s balance ability.     

品管圈在植入式静脉输液港患者护理中的应用

目的探讨品管圈在植入式静脉输液港(IVAP)患者护理中的应用。方法选取本院2018年10月-2018年12月IVAP患者30例作为对照组,2019年1月-2019年3月品管圈活动干预后IVAP患者30例作为观察组。对照组采用常规护理措施,观察组采用品管圈活动干预后的护理措施。比较两组IVAP患者并发症的发生率和对护理工作的满意度。结果观察组导管堵塞1例;并发症发生率为3.33%(1/30)。对照组感染4例,血栓2例,导管堵塞4例;并发症发生率为33.33%(10/30)。观察组并发症发生率低于对照组(P <0.05)。观察组对优质服务、技术水平、关怀、出院指导、护理总满意度评分分别为(42.39±5.27)分、(31.49±4.32)分、(22.25±4.69)分、(20.26±4.91)分、(112.24±10.38)分;对照组分别为(38.65±4.91)分、(28.68±4.26)分、(19.96±4.30)分、(19.94±4.63)分、(103.37±10.12)分;观察组对优质服务、技术水平、关怀、出院指导、护理总满意度评分均高于对照组(P <0.05)。结论通过品管圈活动干预后的护理措施明显降低IVAP患者并发症的发生率,提高患者对护理工作的满意度。     

论当前疾病预防控制体系面临的主要问题

对当前的疾病预防控制体系和机构面临的体系不健全、政府投入不充分、事业发展不平衡、人才缺失和能力不足、缺乏系统的理论指导、体系的碎片化严重、与社会经济发展的战略衔接不力、机构内部内生动力和活力不足以及体系治理能力不足等问题做了讨论分析,以期进一步分析在健康中国战略和事业单位机构改革等宏观环境变化所带来的机遇以及疾控体系的发展策略和具体措施,促进疾病预防控制事业在改革中谋发展。     

A Proposal for an Alternative Approach to Particle Size Method Development During Early-Stage Small Molecule Pharmaceutical Development

Particle size analysis in the pharmaceutical industry has long been a source of debate regarding how best to define measurement accuracy; the degree to which the result of a measurement or calculation conforms to the true value. Defining a “true” value for the size of a particle can be challenging as the output of its measurement will differ because of variations in measurement approaches, instrumental differences and calculation methods. Consequently, for “real” particles, a universal “true” value does not exist and accuracy is therefore not a definable characteristic. Accordingly, precision is then a measure of the ability to reproducibly achieve a measurement of unknown relevance.This article proposes, in place of accuracy, a means to define the “appropriateness” of a measurement in line with the critical quality attributes (CQA) of the material being characterized. The decision as to whether the measurement is correct should involve a link to the CQA; that is, correlation should be demonstrated, without which the measured particle size cannot be defined as a critical material attribute.Correspondingly, methods should also be able to provide sufficient precision to demonstrate discrimination relating to variation in the CQA. The benefits and challenges of this approach are discussed.