大负荷运动后时钟基因Bmal1调控骨骼肌线粒体结构功能的作用机制

目的:探讨大负荷运动后大鼠骨骼肌时钟基因Bmal1节律振荡变化及其对线粒体结构功能的调控作用。方法:将156只成年SD大鼠随机分为对照组和运动组,运动组予以一次大负荷运动训练。每6 h取各组大鼠腓肠肌,使用RT-qPCR检测各时相时钟基因Bmal1的mRNA水平,并用余弦分析软件CircaCompare(R Packages)获取拟合余弦曲线参数,分析时钟基因Bmal1的mRNA表达节律性振荡情况,透射电镜下观察每周期始末(ZT0、ZT24、ZT48和ZT72)骨骼肌线粒体的形态学变化,Western blot检测Bmal1和过氧化物酶体增殖物激活受体γ辅激活因子1α(peroxisome proliferator activated receptorγcoactivator-1α,PGC-1α)的蛋白表达,ELISA测定ATP和ADP含量,以及线粒体氧化呼吸链酶细胞色素C氧化酶复合物亚单位Ⅱ(subunitsⅡof cytochrome C oxidase complex,COXⅡ)和COXⅣ的活性。结果:运动组Bmal1的mRNA表达在ZT0~ZT24时节律出现紊乱(P>0.05),ZT24~ZT48和ZT48~ZT72时节律恢复(P<0.05)。大负荷运动后运动组线粒体形态于ZT0出现肿胀、嵴结构损伤等异常,于ZT24和ZT48时有所恢复,ZT72时损伤基本消失。与对照组相比,运动组Bmal1、PGC-1α的蛋白表达于ZT0时显著升高(P<0.05),ATP和ADP含量分别于ZT0时显著下降和升高(P<0.05),COXⅡ和COXⅣ活性于ZT0时显著升高和下降(P<0.05),在ZT24时二者活性下降至最低(P<0.05)。结论:大负荷运动可诱发骨骼肌时钟基因Bmal1的节律紊乱,可能参与调控了线粒体的结构功能异常。     

Upper limb function and activity in people with facioscapulohumeral muscular dystrophy: a web-based survey

Purpose To investigate the upper extremity (UE) at the level of impairments and related activity limitations and participation restrictions in people with facioscapulohumeral muscular dystrophy (FSHD). Methods The study was conducted using web-based questionnaires that were distributed amongst people with FSHD in the Netherlands. Eighty-eight respondents started the survey, and 71 completed it. The questionnaires covered the following dimensions: Function, Activity and Participation of the International Classification of Functioning Disability and Health. Results More than 40% of the respondents experienced pain in one arm or both the arms. Increased pain and stiffness scores and longer disease duration were associated with increased limitation scores. For basic activities, lifting the arm above shoulder-level was most frequently reported as most limited, coherent with the clinical picture of FSHD. Among the respondents, 50% indicated restrictions at school, 78% indicated restrictions at work and more than 80% indicated restrictions whilst participating in sports, hobbies, household activities and romantic relationships. Conclusions This study has shown that alongside the well-known problem of lifting the arms above shoulder-level, UE activities below shoulder height during vocational and occupational activities are also problematic in patients with FSHD. Alongside disease duration, pain and stiffness are associated with UE activity limitations.

• Implications for Rehabilitation

• Attention is needed for pain and experienced stiffness in the upper extremity as it is frequently present in patients with FSHD.

• Rehabilitation professionals need to be aware that patients with FSHD not only experience problems with activities above shoulder height, but also with activities below shoulder height.

• At least 50% of the patients with FSHD experience restrictions in participation as a result of limitations in their UE.

     

miR-145对血管平滑肌细胞生物活性及SM22α mRNA表达的作用*

目的：探究miR-145 对血管平滑肌细胞（VSMC）的生物活性及对SM22α mRNA 表达的作用。方法： VSMC分为3 组,增殖VSMC组（ 增殖组）、增殖VSMC + 转染miR-145-NC 组（ 空载体组）、增殖VSMC+转染 miR-145 组（ 增殖转染组）。采用RT-PCR 检测VSMC中SM22α mRNA、miR-145 的表达;免疫印迹检测cyclin E、p27 蛋白水平;Transwell 小室检测VSMC侵袭能力;MTT检测VSMC活力;流式细胞术检测VSMC凋亡率。 结果：增殖组VSMC中SM22α mRNA、miR-145 水平与空载体组相比数值较为接近;与增殖组及空载体组相比, 增殖转染组VSMC中miR-145、SM22α mRNA 表达升高。增殖组VSMC中cyclin E、p27 蛋白水平与空载体组相 比无差异;增殖转染组cyclin E 蛋白水平低于空载体组、增殖组,p27 蛋白水平高于空载体组、增殖组。增殖组 VSMC迁移数量与空载体组相比无差异;增殖转染组VSMC迁移数量明显低于空载体组、增殖组。增殖组与空载 体组VSMC在不同时间点的OD 值均较为接近;增殖转染组OD 值在不同时间点均低于空载体组、增殖组。增殖 组VSMC凋亡率与空载体组数值接近,组间比较差距较小;增殖转染组VSMC凋亡率较空载体组和增殖组升高。 结论：过表达miR-145 通过促进SM22α 水平增加,抑制血管平滑肌细胞的增殖,并促进其凋亡。     

Advising people with back pain to take time off work: a survey examining the role of private musculoskeletal practitioners in the UK

Research has demonstrated that health care practitioners’ adherence to guidelines for managing low back pain (LBP) remain suboptimal in recommending work absence, but specific beliefs about their role in maintaining patients at work have not been adequately researched. We examined private musculoskeletal practitioners’ (chiropractors, osteopaths, and physiotherapists) beliefs and reported clinical behaviours in reference to patients’ work. A cross-sectional postal questionnaire of 900 musculoskeletal practitioners included the Attitudes to Back pain in musculoskeletal practitioners questionnaires, reported frequency of four work-related behaviours, and a new measure of practitioners’ work-related beliefs. Data from 337 respondents (37%) were analysed. Eighty percent of respondents reported recommending work absence to patients with LBP sometimes, and 14% recommended a work absence often or always. Seventy percent of practitioners never visit the patient’s workplace. Most practitioners report that they prescribe exercises that can be carried out at work. Physiotherapists visited the workplace more frequently and gave less sick leave certification than either of the other groups. They also regarded work as more beneficial and less of a threat to exacerbate patients’ LBP. There were small but significant correlations between work-related beliefs and reported behaviours. Our study confirms that, in contrast to current guidelines, many practitioners believe that LBP necessitates work absence. Overall, practitioners perceived their role in returning patients to work as limited, and believed that direct contact with employers was beyond their remit. In the UK, physiotherapists appear to be better placed to liaise with work in terms of both their beliefs and activities.     

Management Strategies for Pain in Breast Carcinoma Patients: Current Opinions and Future Perspectives

Breast cancer is the most frequently encountered carcinoma in women worldwide. Pain is the most distressing symptom in patients with breast carcinoma and can occur at all stages of the disease due to the cancer per se as well as due to various diagnostic and treatment modalities. A proper pain assessment helps in identification of pain syndromes and guides in formulating analgesic strategies. Primary therapies of breast carcinoma like surgery, chemotherapy, and radiotherapy for bony metastases can cause substantial pain relief. However, multimodal analgesic approaches incorporating pharmacological, interventional as well as non-conventional techniques should be employed prior to, in conjunction with, and after primary therapies of breast cancer. The prevalence of chronic neuropathic pain following breast cancer surgery may exceed 50% by current estimates, and with the increase in life expectancy of these patients, providing adequate pain relief is of paramount importance to improve their quality of life. In this review, we discuss prevailing methods of evaluation and management of pain in patients of breast carcinoma and the new techniques that may become the mainstay of pain management protocols in future.     

Sleep onset insomnia symptoms during hospitalization for major burn injury predict chronic pain

Both cross-sectional studies of chronic pain and sleep deprivation experiments suggest a bi-directional relationship between sleep and pain. Few longitudinal studies, however, have assessed whether acute insomnia following traumatic injury predicts the development of persistent pain. We sought to evaluate (1) whether in-hospital insomnia independently predicts long-term pain after burn injury and (2) whether in-hospital pain predicts future insomnia symptoms. We analyzed data on 333 subjects hospitalized for major burn injury (72.7% male; mean age=41.1+/-14.5years) who were participating in the multi-site, Burn Model System project. Subjects completed measures of health, function (SF-36), and psychological distress (Brief Symptom Inventory) while in hospital, at 6, 12, and 24months after discharge. Participants were categorized as either having or not having sleep onset insomnia at discharge. Linear mixed effects analyses revealed that persons reporting insomnia at discharge (40.5%) had significantly decreased improvement in pain and increased pain severity during long-term follow-up (p<0.001). More severe pain during the week preceding hospital discharge, time from injury, lack of college education and older age also contributed independent effects on chronic pain (p<0.05). In a reciprocal model (N=299), more severe pain during the week preceding discharge predicted increased rates of long-term sleep onset insomnia. In-hospital insomnia and pre-burn mental health symptoms were also highly significant predictors of insomnia. This study provides support for a long-term, prospective and reciprocal interaction between insomnia and pain. Future work should ascertain whether treatment of insomnia and pain during acute injury can prevent or minimize chronic pain.     

超声造影剂Optison介导质粒GFP转染小鼠骨骼肌细胞的实验研究

目的 探讨微泡造影剂Optison介导基因转染小鼠骨骼肌细胞的作用.方法 采用质粒GFP作为目的基因,超声(1 MHz脉冲波,20%工作周期,空间时间峰值强度1 W/cm2)结合Optison作用于小鼠体外H2K成肌细胞,照射时间分别为10、20、30、40、50及60 s,流式细胞仪测定GFP阳性细胞率,台盼蓝染色测定细胞生存率.超声结合Optison作用于小鼠胫前肌,1周后处死小鼠,荧光显微镜检测GFP阳性肌纤维数,HE染色后计算肌肉损伤面积.结果 活体外细胞实验结果显示,与阳性对照组相比,Optison结合超声作用于H2K细胞10、20及30 s时,显著增强GFP基因表达水平(P＜0.01),但于40、50及60 s时基因表达水平显著降低(P＜0.01),细胞死亡率总体显著增加(P＜0.01).动物实验结果显示,Optison单独或结合超声均显著增强GFP基因表达水平,且Optison单独作用显著减少肌肉损伤面积.结论 Optison可显著增强活体小鼠骨骼肌细胞基因表达水平,同时具有肌肉保护作用.