电脑前久坐易出现肌肉骨骼疼痛

一项新的研究显示,大学生花在电脑上的时间越长,越有可能在当天出现肌肉和骨骼疼痛的问题。[第一段]     

肌肉骨骼减少症发病机制及其运动防治效果

肌肉骨骼减少症（osteosarcopenia,OS）是一种多因素、多病因的退行性代谢综合征,其影响因素可能与衰老导致的机械、遗传、炎症因子、内分泌紊乱以及生活方式不规律相关。OS患者具有更高跌倒、骨折、活动障碍和死亡的风险,随着中国全球老龄化进程的加快,OS已经成为不容忽视的公共健康问题。近年来,国内外学者针对OS开展了大量的研究,但其发病机制仍不清楚。了解与OS相关的信号通路对进一步研究其发病机制和寻找治疗的新靶点具有重要意义。而运动作为现有效果强、持续性好的非药物治疗方式,能够增加老年人肌肉质量、提高骨密度、改善生活质量等,从而有效地预防和改善OS。本文主要就OS的流行病学、诊断标准、共同参与调节肌细胞与骨骼细胞代谢过程的相关信号通路（PI3K/Akt通路、Wnt/β-catenin通路、Notch通路、NF-κB通路）,以及不同运动方式对OS的干预效果等方面进行综述,以期为临床治疗OS提供理论依据,提高老年疾病的预防能力。     

NLRP3炎性小体在肌肉骨骼系统疾病中的作用

炎性小体是先天性免疫系统的受体和传感器,在许多疾病的发生和进展中起着关键的病理作用。近期研究表明,NOD样受体家族核苷酸结合寡聚化结构域样受体3 (NOD-like receptor thermal protein domain associated protein 3, NLRP3)炎性小体参与了对公共健康具有高度影响的疾病的发生,如肌肉骨骼系统疾病。肌肉骨骼系统疾病是主要由工作和周围环境引起或加重的肌肉、关节、骨骼等运动系统疾病,以及相关神经、循环系统损伤的疾病。NLRP3小体的激活可以诱导炎症及引发焦亡,造成机体进一步损伤。因此,以NLRP3炎性小体为切入点,开展对肌肉骨骼系统疾病的预防和治疗具有重要意义。研究炎症性疾病中NLRP3炎性小体活动的机制及作用已然成为新的研究方向。本文对NLRP3炎性小体的激活途径及机制进行了概述,并分析了NLRP3炎性小体在肌少症、骨质疏松症和关节炎等肌肉骨骼系统疾病中的作用,以期为肌肉骨骼系统疾病的治疗提供理论依据。     

二维心室建模和Brugada综合症仿真

本文以Tusscher提出的人体心室单细胞计算模型为基础,用计算机建模仿真的方法,构建一个心室壁组织的二维网格模型。通过修改细胞的离子通道参数,仿真了正常生理条件下和Brugada症状下三类心室细胞的动作电位和心电图波形。结果显示:Brugada症状下的心电图波形有明显的J波出现,ST-段抬高甚至T波倒置。这与临床医学上的报道基本符合,本研究为用计算机仿真建模研究Brugada综合症打下了基础。     

同胚模型——生物系统建模与仿真的一个发展方向

本文叙述了自系统论、控制论提出以来生物系统的建模与仿真的几种类型各自的优缺点,包括类比模型、黑箱模型、机能模型以及同胚模型,指出建立同胚模型是生命科学定量化较好的发展,最后提出了建立同胚模型的几种可能的方法。     

肌肉因子对骨骼肌纤维类型转化的作用及机制研究进展

骨骼肌纤维类型转化是极其复杂且重要的生理过程,影响骨骼肌肌肉功能和代谢水平,不仅受到外界环境变化的影响,还受内在生理机制的调控。因此深入探究肌纤维类型转化的生理过程对于治疗人类神经肌肉疾病以及提高家畜肉质具有重要意义。由骨骼肌分泌的细胞因子,即肌肉因子,对骨骼肌纤维类型转化具有重要作用,主要通过自分泌和旁分泌的形式作用于骨骼肌,参与骨骼肌内信号传导,调控肌纤维类型转化。本文介绍了各种骨骼肌纤维类型间的功能差异,并对影响不同骨骼肌纤维类型转化过程的肌肉因子及其调控肌纤维类型转化的作用及机制进行综述和展望,为改善家畜肉质和治疗骨骼肌相关疾病提供了理论依据。     

E2F家族对肌肉骨骼系统发育和相关疾病的影响

E2F家族是介导腺病毒E1a诱导E2基因的转录因子家族,在调控细胞周期进程、调节细胞增殖、诱导细胞凋亡的过程中起着至关重要的作用。鉴于其功能主要与细胞增殖分化有关,早期关于E2F家族的研究多集中于E2F与癌症的关系。随着研究范围的不断扩大,研究者发现,E2F家族在肌肉骨骼系统的发育过程以及相关疾病的作用机制中独立发挥作用。E2F家族可以通过调控干细胞、成骨细胞、破骨细胞、软骨细胞和成肌细胞的细胞周期和增殖过程,并且作为多个通路下游以及微RNA（microRNA）的靶点基因,减缓或加重肌肉骨骼系统疾病进展。目前关于E2F家族在肌肉骨骼系统中的作用还没有系统的总结和梳理,本文主要就E2F家族在肌肉骨骼系统中的生理学功能和E2F家族在肌肉骨骼系统相关疾病中的作用机制进行综述,希望为后续研究和疾病诊疗提供依据。     

面向短QT综合征的药物作用建模与仿真研究

短QT综合征(short QT syndrome,SQTS)是以心电图QT间期、心室和心房不应期明显缩短为主要显性特征,并伴有晕厥、高发心源性猝死(sudden cardiac death,SCD)和恶性心律失常风险的一类遗传性心肌离子通道病.据目前资料信息,关于SQTS致病机理的报道比较多,而对SQTS药物治疗的报道罕见.为了揭示在SQTS下的药物作用,本文通过计算机仿真构建人体心室细胞和组织的药物作用模型,利用该模型,从亚细胞、细胞、组织三个尺度,模拟SQT1、SQT2和SQT3下的普罗帕酮药物作用过程,并仿真心电图的变化情况.仿真结果表明:在SQT1下普罗帕酮延长了动作电位时程(action potential duration,APD)和心电图QT间期,并降低T波幅值;相反,在SQT2和SQT3下普罗帕酮缩短了APD和QT间期.计算使用药物前后细胞间膜电压和APD空间离散度的变化,定量分析了普罗帕酮降低T波振幅的原因.总之,对SQT1,普罗帕酮有效;对SQT2和SQT3,普罗帕酮没有改变其致心律失常的危险.仿真结果为普罗帕酮用于临床治疗SQTS提供理论参考.     

仿真领域的持续承诺

随着分子生物学领域的进步,基因组及相关计划的进展,系统生物学逐渐成为生命科学研究中的热点,生物系统方面的建模和仿真也成为目前系统生物学研究引人关注的内容之一。而第一代建模工具在应用的过程中存在许多缺陷,从而导致用户需求和工具建模能力之间存在巨大鸿沟。本文对第一代建模工具存在的问题进行了分析,并简单介绍了可以进行复杂仿真建模的新一代仿真工具。此外,文章对系统生物学的市场模式也进行了探讨。     

A Model of Human Muscle Energy Expenditure

A model of muscle energy expenditure was developed for predicting thermal, as well as mechanical energy liberation during simulated muscle contractions. The model was designed to yield energy (heat and work) rate predictions appropriate for human skeletal muscle contracting at normal body temperature. The basic form of the present model is similar to many previous models of muscle energy expenditure, but parameter values were based almost entirely on mammalian muscle data, with preference given to human data where possible. Nonlinear phenomena associated with submaximal activation were also incorporated. The muscle energy model was evaluated at varying levels of complexity, ranging from simulated contractions of isolated muscle, to simulations of whole body locomotion. In all cases, acceptable agreement was found between simulated and experimental energy liberation. The present model should be useful in future studies of the energetics of human movement using forward dynamic computer simulation.     

Finger Muscle Attachments for an OpenSim Upper-Extremity Model

We determined muscle attachment points for the index, middle, ring and little fingers in an OpenSim upper-extremity model. Attachment points were selected to match both experimentally measured locations and mechanical function (moment arms). Although experimental measurements of finger muscle attachments have been made, models differ from specimens in many respects such as bone segment ratio, joint kinematics and coordinate system. Likewise, moment arms are not available for all intrinsic finger muscles. Therefore, it was necessary to scale and translate muscle attachments from one experimental or model environment to another while preserving mechanical function. We used a two-step process. First, we estimated muscle function by calculating moment arms for all intrinsic and extrinsic muscles using the partial velocity method. Second, optimization using Simulated Annealing and Hooke-Jeeves algorithms found muscle-tendon paths that minimized root mean square (RMS) differences between experimental and modeled moment arms. The partial velocity method resulted in variance accounted for (VAF) between measured and calculated moment arms of 75.5% on average (range from 48.5% to 99.5%) for intrinsic and extrinsic index finger muscles where measured data were available. RMS error between experimental and optimized values was within one standard deviation (S.D) of measured moment arm (mean RMS error = 1.5 mm < measured S.D = 2.5 mm). Validation of both steps of the technique allowed for estimation of muscle attachment points for muscles whose moment arms have not been measured. Differences between modeled and experimentally measured muscle attachments, averaged over all finger joints, were less than 4.9 mm (within 7.1% of the average length of the muscle-tendon paths). The resulting non-proprietary musculoskeletal model of the human fingers could be useful for many applications, including better understanding of complex multi-touch and gestural movements.     

An Ecological Risk Management and Capacity Building Model

Worldwide, natural and human ecosystems are increasingly subjected to natural hazards due to global environmental change. Because these threats reflect interaction between social and ecological systems, effective Disaster Risk Reduction (DRR) can best be accomplished by increasing community capacity to mitigate, cope with, adapt to, and recover from hazard consequences by developing DRR strategies that accommodate natural and human ecosystem interdependency. One reason of the widespread ineffectiveness in preparedness has been the neglect of environment/community interactions, and how community and individual variables interact with each other. To address this gap an all-hazard and inter-disciplinary literature review was conducted that synergized and integrated individual-level and environment/community-level factors. Based on the review a social-ecological model was developed. This model identifies a multitude of variables operating across a wide range of dimensions (i.e., individual, historical, physical/natural, social, spiritual/religious, economic, political) and different scales (i.e., individual, household, community organisations, businesses, local government, state government). Based on the review a holistic ecological all-hazard inter-disciplinary risk management and capacity building model was developed that describes how these factors interact to influence risk management and adaptive capacities. This holistic model provides a foundation and rationale for facilitating the capacity of all stakeholders in at-risk areas to develop comprehensive social-ecological relationships and researchers to investigate human-environment interactions in depth.     

An In Vitro Model of Skeletal Muscle Volume Regulation

Introduction

Hypertonic media causes cells to shrink due to water loss through aquaporin channels. After acute shrinkage, cells either regulate their volume or, alternatively, undergo a number of metabolic changes which ultimately lead to cell death. In many cell types, hypertonic shrinkage is followed by apoptosis. Due to the complex 3D morphology of skeletal muscle and the difficulty in obtaining isolated human tissue, we have begun skeletal muscle volume regulation studies using the human skeletal muscle cell line TE671RD. In this study we investigated whether hypertonic challenge of the human skeletal muscle cell line TE671RD triggered cell death or evoked a cell volume recovery response.

Methods

The cellular volume of TE671RD cells was calculated from the 2D surface area. Cell death was assessed by both the trypan blue live/dead assay and the TUNEL assay.

Results

Medium osmolality was increased by addition of up to 200mM sucrose. Addition of 200mM sucrose resulted in mean cell shrinkage of 44±1% after 30mins. At later time points (2 and 4 hrs) two separate cell subpopulations with differing mean cell volume became apparent. The first subpopulation (15±2% of the total cell number) continued to shrink whereas the second subpopulation had an increased cell volume. Cell death was observed in a small proportion of cells (approximately 6-8%).

Conclusion

We have established that a substantial proportion of TE671RD cells respond to hypertonic challenge with RVI, but that these cells are resistant to hypertonicity triggered cell death.     

Mouse Model of Muscle Crush Injury of the Legs

Because crush injury to skeletal muscle is an important cause of morbidity in natural disaster and battlefield settings, a reproducible and refined animal model of muscle crush injury is needed. Both open and closed small-animal models of skeletal muscle crush injury are available but are limited by their need for surgical isolation of the muscle or by the adverse effect of fibular fracture, respectively. In the current study, we developed and validated a novel, noninvasive mouse model of lower-extremity muscle crush injury. Despite the closed nature of our model, gross evidence of muscle damage was evident in all mice and was verified microscopically through hematoxylin and eosin staining. The injury elicited both neutrophil and macrophage infiltration at 24 and 48 h after injury. The area percentage and mean antigen area of F4/80-positive macrophages were higher at 48 h than at 24 h after injury, and CD68-positive macrophage area percentage and mean antigen area differed significantly between injured and uninjured muscle. In addition, the incidence of fibular fracture was one third lower than that reported for an alternative noninvasive model. In conclusion, our model is a reproducible method for muscle crush injury in the mouse pelvic limb and is a refinement of previous models because of its decreased bone fractures and reduction of animal numbers.Abbreviations: AOI, area of interestSkeletal muscle crush injury is an important cause of morbidity in both civilian and military populations. During earthquakes, tornados, and other natural disasters, collapsed structures result in crush injuries in approximately 40% of victims entrapped in the rubble,¹⁴ and crush injuries sustained during these events primarily affect skeletal muscle tissue.¹³ Crush injuries to skeletal muscle received during military conflict can occur when a limb is compressed for an extended time period, and combat-related crush injuries of the extremities frequently are present in wounded troops who are transported via aeromedical evacuation.²²A muscle-crush injury is induced when pressure is applied to skeletal muscle, interrupting blood flow and damaging the cell membranes of the muscle fibers. Several animal models of skeletal muscle-crush injury are used to study the pathophysiology of acute muscle inflammation and to investigate potential therapies.^{1,2,3,5,8,9,12,17,18,21} The most common model is the application of force to a surgically isolated pelvic limb muscle by using a clamp.¹⁶ Although closed models have been investigated, these studies typically involve dropping weights onto rodents’ pelvic limbs, thereby increasing the adverse event of fractures. Although not often reported in the literature, the incidence of fibular fractures in rats as a result of the dropped weight was 27% in one study.³ An additional drawback to the dropped-weight model is that it simulates a high-force contusion injury and does not provide the ischemic effect of the continuous pressure applied by the open clamp model. The ideal crush-injury model would mimic a force-induced injury, because 40% of survivors trapped in building rubble develop ischemia-induced crush syndrome.¹⁴We chose to investigate a novel model of closed crush injury for several reasons. An animal model of skeletal muscle injury should mimic the human clinical presentation, and a closed model more closely simulates a real-world crush injury. Second, because the incision created in the open model can activate the inflammatory response, a group of sham-operated animals is needed to control for the variable of the incision-induced inflammation. By using a closed model, the contralateral limb can serve as the uninjured control, thereby reducing the number of animals needed to perform the study. Last, the closed model represents a refinement of the crush injury procedure by removing the additional tissue damage and inflammation that result from the incision and tissue dissection of the surgical procedure and by reducing the incidence of fractures.Because this model has not been described in the literature, the objective of the current study was to develop a closed, sustained-force model of lower-extremity crush injury that induces a measurable leukocyte response and minimizes damage to nearby bones. In addition, we used monoclonal antibodies to characterize the leukocyte populations associated with this skeletal muscle crush injury model.     

A Rat Model for Muscle Regeneration in the Soft Palate

Background

Children with a cleft in the soft palate have difficulties with speech, swallowing, and sucking. Despite successful surgical repositioning of the muscles, optimal function is often not achieved. Scar formation and defective regeneration may hamper the functional recovery of the muscles after cleft palate repair. Therefore, the aim of this study is to investigate the anatomy and histology of the soft palate in rats, and to establish an in vivo model for muscle regeneration after surgical injury.

Methods

Fourteen adult male Sprague Dawley rats were divided into four groups. Groups 1 (n = 4) and 2 (n = 2) were used to investigate the anatomy and histology of the soft palate, respectively. Group 3 (n = 6) was used for surgical wounding of the soft palate, and group 4 (n = 2) was used as unwounded control group. The wounds (1 mm) were evaluated by (immuno)histochemistry (AZAN staining, Pax7, MyoD, MyoG, MyHC, and ASMA) after 7 days.

Results

The present study shows that the anatomy and histology of the soft palate muscles of the rat is largely comparable with that in humans. All wounds showed clinical evidence of healing after 7 days. AZAN staining demonstrated extensive collagen deposition in the wound area, and initial regeneration of muscle fibers and salivary glands. Proliferating and differentiating satellite cells were identified in the wound area by antibody staining.

Conclusions

This model is the first, suitable for studying muscle regeneration in the rat soft palate, and allows the development of novel adjuvant strategies to promote muscle regeneration after cleft palate surgery.     

A Building Block Model for Quantitative Genetics

We introduce a quantitative genetic model for multiple alleles which permits the parameterization of the degree, D, of dominance of favorable or unfavorable alleles. We assume gene effects to be random from some distribution and independent of the D's. We then fit the usual least-squares population genetic model of additive and dominance effects in an infinite equilibrium population to determine the five genetic components--additive variance sigma 2 a, dominance variance sigma 2 d, variance of homozygous dominance effects d2, covariance of additive and homozygous dominance effects d1, and the square of the inbreeding depression h--required to treat finite populations and large populations that have been through a bottleneck or in which there is inbreeding. The effects of dominance can be summarized as functions of the average, D, and the variance, sigma 2 D. An important distinction arises between symmetrical and nonsymmetrical distributions of gene effects. With symmetrical distributions d1 = -d2/2 which is always negative, and the contribution of dominance to sigma 2 a is equal to d2/2. With nonsymmetrical distributions there is an additional contribution H to sigma 2 a and -H/2 to d1, the sign of H being determined by D and the skew of the distribution. Some numerical evaluations are presented for the normal and exponential distributions of gene effects, illustrating the effects of the number of alleles and of the variation in allelic frequencies. Random additive by additive (a*a) epistatic effects contribute to sigma 2 a and to the a*a variance, sigma 2/aa, the relative contributions depending on the number of alleles and the variation in allelic frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)     

TWEAK Regulates Muscle Functions in a Mouse Model of RNA Toxicity

Myotonic dystrophy type 1 (DM1), the most common form of muscular dystrophy in adults, is caused by toxic RNAs produced from the mutant DM protein kinase (DMPK) gene. DM1 is characterized by progressive muscle wasting and weakness. Therapeutic strategies have mainly focused on targeting the toxic RNA. Previously, we found that fibroblast growth factor-inducible 14 (Fn14), the receptor for TWEAK, is induced in skeletal muscles and hearts of mouse models of RNA toxicity and that blocking TWEAK/Fn14 signaling improves muscle function and histology. Here, we studied the effect of Tweak deficiency in a RNA toxicity mouse model. The genetic deletion of Tweak in these mice significantly reduced muscle damage and improved muscle function. In contrast, administration of TWEAK in the RNA toxicity mice impaired functional outcomes and worsened muscle histopathology. These studies show that signaling via TWEAK is deleterious to muscle in RNA toxicity and support the demonstrated utility of anti-TWEAK therapeutics.