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     

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.     

针刺干预对单眼视觉剥夺模型大鼠视皮层方位柱“漂移”和异常重组的调节作用及其脑功能机制

探讨针刺干预对大鼠单眼视觉剥夺后视皮层方位柱“漂移”和通道重组的影响，初步阐明其作用机制。     

EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer—2020 Update. Part 1: Screening,Diagnosis, and Local Treatment with Curative Intent

ObjectiveTo present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on screening, diagnosis, and local treatment of clinically localised prostate cancer (PCa).Evidence acquisitionThe panel performed a literature review of new data, covering the time frame between 2016 and 2020. The guidelines were updated and a strength rating for each recommendation was added based on a systematic review of the evidence.Evidence synthesisA risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. Risk-adapted screening should be offered to men at increased risk from the age of 45 yr and to breast cancer susceptibility gene (BRCA) mutation carriers, who have been confirmed to be at risk of early and aggressive disease (mainly BRAC2), from around 40 yr of age. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is performed, a combination of targeted and systematic biopsies must be offered. There is currently no place for the routine use of tissue-based biomarkers. Whilst prostate-specific membrane antigen positron emission tomography computed tomography is the most sensitive staging procedure, the lack of outcome benefit remains a major limitation. Active surveillance (AS) should always be discussed with low-risk patients, as well as with selected intermediate-risk patients with favourable International Society of Urological Pathology (ISUP) 2 lesions. Local therapies are addressed, as well as the AS journey and the management of persistent prostate-specific antigen after surgery. A strong recommendation to consider moderate hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term hormonal treatment.ConclusionsThe evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for their use in clinical practice. These PCa guidelines reflect the multidisciplinary nature of PCa management.Patient summaryUpdated prostate cancer guidelines are presented, addressing screening, diagnosis, and local treatment with curative intent. These guidelines rely on the available scientific evidence, and new insights will need to be considered and included on a regular basis. In some cases, the supporting evidence for new treatment options is not yet strong enough to provide a recommendation, which is why continuous updating is important. Patients must be fully informed of all relevant options and, together with their treating physicians, decide on the most optimal management for them.     

Association of regional socioeconomic deprivation and rurality with global developmental delay in early childhood: Data from mandatory school entry examinations in Germany

BackgroundFrom birth to young adulthood, health and development of young people are strongly linked to their living situation, including their family’s socioeconomic position (SEP) and living environment. The impact of regional characteristics on development in early childhood beyond family SEP has been rarely investigated. This study aimed to identify regional predictors of global developmental delay at school entry taking family SEP into consideration.MethodWe used representative, population-based data from mandatory school entry examinations of the German federal state of Brandenburg in 2018/2019 with n=22,801 preschool children. By applying binary multilevel models, we hierarchically analyzed the effect of regional deprivation defined by the German Index of Socioeconomic Deprivation (GISD) and rurality operationalized as inverted population density of the children’s school district on global developmental delay (GDD) while adjusting for family SEP (low, medium and high).ResultsFamily SEP was significantly and strongly linked to GDD. Children with the highest family SEP showed a lower odds for GDD compared to a medium SEP (female: OR=4.26, male: OR=3.46) and low SEP (female: OR=16.58, male: OR=12.79). Furthermore, we discovered a smaller, but additional and independent effect of regional socioeconomic deprivation on GDD, with a higher odds for children from a more deprived school district (female: OR=1.35, male: OR=1.20). However, rurality did not show a significant link to GDD in preschool children beyond family SEP and regional deprivation.ConclusionFamily SEP and regional deprivation are risk factors for child development and of particular interest to promote health of children in early childhood and over the life course.     

Exploiting the tumor-suppressive activity of the androgen receptor by CDK4/6 inhibition in castration-resistant prostate cancer

1. Download : Download high-res image (147KB)
2. Download : Download full-size image

     

形觉剥夺性高度近视豚鼠巩膜形态改变及缺氧诱导因子-1α和氧自由基在高度近视中的作用

目的　观察形觉剥夺性高度近视（form deprivation high myopia，FDHM）豚鼠巩膜形态变化，探讨缺氧诱导因子-1α（hypoxia-inducible factor-1α，HIF-1α）及氧自由基在高度近视中的作用。方法　将豚鼠适应性饲养1周后，随机分为空白对照组（25只）和模型组（25只）。模型组豚鼠右眼行眼睑缝合，所有模型组豚鼠均选择右眼作为FDHM组，对侧眼为自身对照组。空白对照组豚鼠不做任何处理。于造模前及造模后8周采用检影镜测量屈光度，A超进行生物测量。形觉剥夺8周以后处死豚鼠，观察巩膜形态和超微结构的变化，测定巩膜HIF-1α相对表达量，超氧化物歧化酶（superoxide dismutase，SOD）活力及丙二醛（malondialdehyde，MDA）的含量。结果　豚鼠形觉剥夺8周以后，FDHM组屈光度从（+3.59±0.33）D变为（-7.96±0.55）D，明显高于空白对照组（+0.89±0.32）D、自身对照组（-0.55±0.49）D（均为P<0.05）；玻璃体腔深度为（4.12±0.13）mm明显高于空白对照组（3.71±0.23）mm和自身对照组（3.93±0.04）mm（均为P<0.05）；眼轴长度为（8.93±0.22）mm明显长于空白对照组（7.95±0.37）mm和自身对照组（8.01±0.15）mm（均为P<0.05）。巩膜组织明显变薄，细胞外基质增多，成纤维细胞密度降低，胶原纤维平均直径减小。FDHM组巩膜中HIF-1α相对表达量、MDA含量明显高于空白对照组和自身对照组，SOD活力明显低于空白对照组和自身对照组（均为P<0.05）。结论　形觉剥夺8周后，豚鼠FDHM眼近视度数明显增加，玻璃体腔深度增加，眼轴延长，巩膜形态发生病理性变化；HIF-1α、SOD、MDA可能参与了FDHM的形成。