高乳酸血症-卒中样发作综合征型线粒体脑肌病一家系两代四例报告

线粒体脑肌病属于罕见性母系遗传病，本文回顾性分析了1家4例高乳酸血症-卒中样发作综合征（MELAS）型线粒体脑肌病患者，其主要表现为卒中样发作、头痛、癫痫、高乳酸血症、肌肉不耐受疲劳、高级智能下降、听力下降和身材矮小等，结合特征性影像学变化、基因检测及肌肉活检明确诊断，并结合文献对只有女儿能将其线粒体DNA（mt-DNA）传递给下一代的母系遗传MELAS型线粒体脑肌病临床特点进行了总结分析，旨在帮助临床认识此病，进一步提高MELAS型线粒体脑肌病的临床诊断率。     

张立平教授治疗消化道术后胃肠功能紊乱经验

消化道术后胃肠功能紊乱影响着患者们的生活质量。张立平教授认为术后胃肠功能紊乱，证属本虚标实，临床治疗当从调理中焦-脾胃肝为切入点，强调"脾胃为本""中焦一体"的治疗思路，总结出脾胃虚弱、肝郁脾虚两个证型，临证时以培土达木为基本治疗原则，辨证论治，临床疗效显著。     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Functional redundancy of type I and type II receptors in the regulation of skeletal muscle growth by myostatin and activin A

Myostatin (MSTN) is a transforming growth factor-β (TGF-β) family member that normally acts to limit muscle growth. The function of MSTN is partially redundant with that of another TGF-β family member, activin A. MSTN and activin A are capable of signaling through a complex of type II and type I receptors. Here, we investigated the roles of two type II receptors (ACVR2 and ACVR2B) and two type I receptors (ALK4 and ALK5) in the regulation of muscle mass by these ligands by genetically targeting these receptors either alone or in combination specifically in myofibers in mice. We show that targeting signaling in myofibers is sufficient to cause significant increases in muscle mass, showing that myofibers are the direct target for signaling by these ligands in the regulation of muscle growth. Moreover, we show that there is functional redundancy between the two type II receptors as well as between the two type I receptors and that all four type II/type I receptor combinations are utilized in vivo. Targeting signaling specifically in myofibers also led to reductions in overall body fat content and improved glucose metabolism in mice fed either regular chow or a high-fat diet, demonstrating that these metabolic effects are the result of enhanced muscling. We observed no effect, however, on either bone density or muscle regeneration in mice in which signaling was targeted in myofibers. The latter finding implies that MSTN likely signals to other cells, such as satellite cells, in addition to myofibers to regulate muscle homeostasis.

Myostatin (MSTN) is a secreted signaling molecule that normally acts to limit skeletal muscle growth (for review, see ref. 1). Mice lacking MSTN exhibit dramatic increases in muscle mass throughout the body, with individual muscles growing to about twice the normal size (2). MSTN appears to play two distinct roles in regulating muscle size, one to regulate the number of muscle fibers that are formed during development and a second to regulate the growth of those fibers postnatally. The sequence of MSTN has been highly conserved through evolution, with the mature MSTN peptide being identical in species as divergent as humans and turkeys (3). The function of MSTN has also been conserved, and targeted or naturally occurring mutations in MSTN have been shown to cause increased muscling in numerous species, including cattle (3–5), sheep (6), dogs (7), rabbits (8), rats (9), swine (10), goats (11), and humans (12). Numerous pharmaceutical and biotechnology companies have developed biologic agents capable of blocking MSTN activity, and these have been tested in clinical trials for a wide range of indications, including Duchenne and facioscapulohumeral muscular dystrophy, inclusion body myositis, muscle atrophy following falls and hip fracture surgery, age-related sarcopenia, Charcot–Marie–Tooth disease, and cachexia due to chronic obstructive pulmonary disease, end-stage kidney disease, and cancer.The finding that certain inhibitors of MSTN signaling can increase muscle mass even in Mstn^−/− mice revealed that the function of MSTN as a negative regulator of muscle mass is partially redundant with at least one other TGF-β family member (13, 14), and subsequent studies have identified activin A as one of these cooperating ligands (15, 16). MSTN and activin A share many key regulatory and signaling components. For example, the activities of both MSTN and activin A can be modulated extracellularly by naturally occurring inhibitory binding proteins, including follistatin (17, 18) and the follistatin-related protein, FSTL-3 or FLRG (19, 20). Moreover, MSTN and activin A also appear to share receptor components. Based on in vitro studies, MSTN is capable of binding initially to the activin type II receptors, ACVR2 and ACVR2B (also called ActRIIA and ActRIIB) (18) followed by engagement of the type I receptors, ALK4 and ALK5 (21). In previous studies, we presented genetic evidence supporting a role for both ACVR2 and ACVR2B in mediating MSTN signaling and regulating muscle mass in vivo. Specifically, we showed that mice expressing a truncated, dominant-negative form of ACVR2B in skeletal muscle (18) or carrying deletion mutations in Acvr2 and/or Acvr2b (13) have significantly increased muscle mass. One limitation of the latter study, however, was that we could not examine the consequence of complete loss of both receptors using the deletion alleles, as double homozygous mutants die early during embryogenesis (22). Moreover, the roles that the two type I receptors, ALK4 and ALK5, play in regulating MSTN and activin A signaling in muscle in vivo have not yet been documented using genetic approaches. Here, we present the results of studies in which we used floxed alleles for each of the type II and type I receptor genes in order to target these receptors alone and in combination in muscle fibers. We show that these receptors are functionally redundant and that signaling through each of these receptors contributes to the overall control of muscle mass.     

以失用为主要表现的胼胝体梗死

目的探讨胼胝体梗死的临床表现、病因及鉴别诊断特点。方法对2005年7月收治的1例53岁男性胼胝体梗死患者的临床表现、影像学特点、病因机制及其治疗过程进行回顾分析。结果临床主要表现为发作性黑蒙、言语不利,既往有高血压、糖尿病、脑梗死、吸烟、饮酒史,体格检查以失用为主要表现。头部MRI检查可见左侧脑室旁、胼胝体梗死,右侧基底节、脑桥陈旧性腔隙性梗死;脑血管造影检查显示为多发性血管狭窄,其中以左侧大脑中动脉、右侧颈内动脉及基底动脉最为严重。经颈内动脉内膜剥离术及颈内动脉支架植入术治疗,临床症状缓解。结论失用可以是胼胝体梗死的主要表现,其病因是在脑动脉粥样硬化基础上的血流动力学改变,患者预后良好。     

64层CT下肢动脉成像技术研究

目的探讨64层CT下肢动脉成像强化质量的对比剂注射方式。方法前瞻性地选择60例疑诊下肢动脉病变的病人,利用64层螺旋CT行下肢动脉CT血管成像。采用不同的扫描和重建参数,应用370mgI/100ml浓度的对比剂100ml团注或采用先70ml的对比剂后50ml的0.9%生理盐水用双筒高压注射器分别以4.0ml/s的注射速度团注入肘静脉,应用对比剂追踪触发扫描方式待腹主动脉CT阈值达120HU时延迟7s开始扫描;利用MIP和VR方式重建CTA图像;对比不同参数和不同对比剂应用方式的CT血管成像图像质量。结果最佳的扫描与重建参数为准直64×0.6mm,螺距1.5,层厚1.0,重建间隔50%;最佳的对比剂应用方式为(浓度为370mgI/100ml)对比剂70ml、生理盐水50ml以4.0ml/s注射速度按先后顺序团注。结论选择合适的准直、螺距以保证适当的扫描速度,选择合适的对比剂浓度、用量和注射速度以保证血管内足够的对比剂峰值浓度及峰值持续时间,此二者是64层CT下肢动脉成像成功的关键。     

膝关节运动过程的应力数值模拟

目的观察膝关节关节面在整个运动过程中的应力、应变分布范围、大小及变化规律。方法利用有限元数值模拟方法对行走过程中膝关节关节面应力、应变情况进行分析。结果与结论行走过程中关节面产生应力、应变随时间推移而增加，并且变化规律近似的服从抛物线变化。通过对不同体重的人在行走时膝关节面上产生的应力分析得出，体重对关节面上的应力的大小并不产生重大影响，体重带来的应力差异仅占总应力的10％。     

胃癌穿孔24例治疗分析

目的 :探讨胃癌穿孔的临床特点 ,指导临床诊治和提高疗效。方法 :对本院 2 4例胃癌穿孔病人采用不同手术方式治疗。其中 8例行单纯修补术 ,2例在穿孔修补术后 3周早期施行二期根治性手术 ,3例行穿孔修补加胃空肠吻合术 ,7例行姑息性胃大部切除术 ,4例行胃癌根治术。结果 :本组死亡 4例 ,其余病例中位生存期分别为 7,13 .2 ,2 5 .1个月。结论 :采取积极的治疗措施 ,可望延长患者的生存时间和提高生存质量