进行性肌营养不良患儿肌肉组织转化生长因子-β_1的表达

目的　进行性肌营养不良肌纤维化的病理机制不清。转化生长因子 β1(TGF β1)能诱导细胞外基质的积聚 ,对纤维发生和组织修复起调节作用。本研究探讨进行性肌营养不良患儿肌肉TGF β1表达与肌纤维化的关系 ,阐明儿童进行性肌营养不良肌纤维化慢性病理进展的部分机制。方法　采用免疫荧光和免疫印迹的方法检测 18例进行性肌营养不良患儿 [7例Duchenne肌营养不良 (DMD) ,6例福山型和 3例非福山型先天性肌营养不良 (FCMD ,nFCMD) ,2例Becker型肌营养不良 (BMD) ]和 13例非神经肌肉疾病患者肌肉组织中TGF β1表达。结果　先天性肌营养不良 (CMD)和DMD肌组织内潜伏和活性形式的TGF β1均免疫定位于肌纤维和间质的肌内膜 ,表达强度以CMD为著。免疫印迹结果显示FCMD肌肉组织TGF β1表达强于DMD和对照。结论　在儿童进行性肌营养不良的肌肉慢性病理进展中 ,肌肉纤维化可能是重要原因之一。     

Duchenne muscular dystrophy: Recent concepts

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease, affecting only males and transmitted by females. Recent proposed pathogeneses are defective DNA repair mechanism and cell-mediated cytotoxicity. Serum CPK estimation is most frequently high (30–300) and is also reliable for detecting carriers. It is important to recognise the affected boys as early as possible. Diagnosis of DMD is made from clinical features, CPK estimation, EMG and ECG abnormalities. The use of agents to reduce influx of intracellular calcium in patients with DMD are emerging for therapeutic consideration. New advance in genetic counselling is the localisation of the gene for DMD using DNA polymorphisms.     

肌特异性microRNA作为杜氏肌营养不良生物标志物的研究进展

microRNA（miRNA）是一种长度约22nt的非编码单链RNA，主要在转录后调控基因的表达。目前miRNA已成为多种疾病潜在的生物标志物，如肿瘤、白血病、神经系统疾病等。肌特异性miRNA在杜氏肌营养不良（DMD）患者的骨骼肌中富集，且在DMD发病机制中起重要作用。鉴于肌酸激酶诊断DMD的特异性有限，如其水平与病情轻重无明显关联，故探索肌特异性miRNA是否能成为理想的DMD生物标志物具有重要临床意义，该文将对这一领域研究进展进行综述。     

Dystrophin Abnormality in Progressive Muscular Dystrophy -A Review Article-

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disorder of muscle in children, with an incidence of approximately 1 in 3,300 male births. In about a third of affected boys, the disease is due to a new mutation, and most patients die in their early 20s. Over the last few years, the genetic, biochemical and histopathological basis of DMD has been elucidated greatly. In particular, the discovery of "dystrophin," the protein product of the DMD gene is truly an epoch-making success in the history of muscular dystrophy research. Dystrophin is now thought to be a cytoskeletal protein underlying the plasma membrane (known in muscle as the sarcolemma) of normal muscle fiber, and is undetectable or greatly reduced in DMD. In this review article, dystrophin in normal skeletal muscle and various neuromuscular diseases including DMD/BMD (Becker muscular dystrophy), and its carrier is discussed.     

进行性肌营养不良患者血浆金属蛋白酶组织抑制剂-1和转化生长因子-β1水平检测(英文)

目的：伴随着肌纤维变性 再生的肌内异常结缔组织增生为肌营养不良的一个特征。金属蛋白酶组织抑制剂 (TIMPs)是多功能蛋白,能改变细胞活性和调节基质转变。转化生长因子 β1(TGF β1)也促进组织纤维化。该文探讨TIMP 1和TGF β1在各种肌营养不良发病机制中的作用。 方法：用ELISA法检测几种肌营养不良患者血浆TIMP 1和TGF β1水平。 结果：Duchenne肌营养不良 (DMD)血浆TIMP 1水平为 12 2 .5 2±6 3.87ng/ml,在先天性肌营养不良 (CMD)为 12 4 .87± 6 3.14ng/ml,较对照组 (85 .71± 2 9.13ng/ml)明显升高 (均P <0 .0 5 ) ,但在Becker型肌营养不良 (BMD)为 86 .93± 4 8.93ng/ml,与对照组比较无明显升高 ;血浆TGF β1水平在DMD为 2 6 .2 6± 5 .79ng/ml,CMD为 31.35± 9.77ng/ml,也较对照组 (6 .2 4± 1.12ng/ml)明显升高 ,差异有显著性 ,均P <0 .0 5 ,但在BMD为 3.4 6± 1.38ng/ml,无升高 ;而且TIMP 1和TGF β1浓度有明显的相关性。结论：血浆TIMP 1和TGF β1水平在DMD和CMD中明显升高 ,而BMD中未见明显升高 ,似乎与肌营养不良的临床严重性相关 ,表明TIMP 1和TGF β1在肌营养不良的发病中可能起作用。     

Membrane changes in Duchenne/Becker muscular dystrophy: lectin binding and localization of dystrophin

An RCA I-lectin binding glycoprotein of Mr = 370 kD is missing from or altered in the plasma membrane of Duchenne muscular dystrophy (DMD) skeletal muscle. In the present study the carbohydrate chain of this glycoprotein was localized to the external face of the plasma membrane in human skeletal muscle, and dystrophin, the protein product of the DMD gene, was localized to the inner (cytoplasmic) face. On double labelled Western blots the two proteins appeared as closely apposed but distinctly separate bands. Comparison of the plasma membrane binding of five lectins with overlapping sugar specificities in skeletal muscle from patients with DMD and the allelic milder disease form, Becker muscular dystrophy (BMD) showed that the RCA I-binding glycoprotein also strongly binds to phytohaemagglutinin, thereby largely characterising the carbohydrate binding site. This glycoprotein was absent or altered in DMD and markedly reduced in clinically manifest BMD but present in preclinical clinical BMD. There was no general depletion of plasma membrane glycoproteins in DMD because consistent plasma membrane binding could be demonstrated by peanut and maclura pomifera lectin. The possible implications of these findings for the pathogenesis of DMD/BMD are discussed.     

Recent developments in the management of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is the most common and severe childhood muscular dystrophy, resulting in progressive muscle weakness and wasting, disability and decreased survival. Although the molecular defect in DMD is known, no curative treatment is available. The treatment options of glucocorticoid corticosteroids and supportive measures, such as ventilation and management of cardiac insufficiency, have become accepted clinical practice in the last decade, and these are of major interest to the paediatrician as they have significantly changed the course of the disease in treated individuals. This has implications not only for the affected individual and his family, but also for the medical and social sectors to provide transition to adult medical services and for provision of suitable employment, and social care.Several experimental therapeutic strategies, including cell and gene therapy, are promising, with encouraging results in relevant animal models and in cultured human cells. As a number of approaches are in early clinical trials, expectations are raised of their impact as a cure for DMD; nevertheless, it is not realistic to expect that these approaches will have a substantial impact on disease course in the short term. While waiting for a curative therapy to become available, symptomatic and palliative treatment is essential to enhance the patient’s quality of life. This review addresses the advances in these therapies aimed at improving function and quality of life in patients with DMD, and the current status of research into the DMD experimental therapies.     

Update on the management of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is familiar to paediatricians as the most common childhood muscular dystrophy and leads to severe disability and early death in the late teenage years if untreated. Improvements in general care, glucocorticoid corticosteroid treatment, non-invasive ventilatory support, and cardiomyopathy and scoliosis management have significantly changed the course of DMD in treated individuals, so that survival into adulthood is now a realistic possibility for most patients. This has important implications for the medical and social sectors involved in the transition to adult medical services and the provision of suitable employment and social care. Multidisciplinary team working for optimal management of DMD-specific multisystem complications is essential, and collaboration in disease specific national clinical networks is recommended. Several curative therapeutic strategies including cell and gene therapy are being pursued but are still at an experimental stage.     

Becker/Duchenne肌营养不良患儿临床表型与基因关联性预测分析

目的 探讨Becker/Duchenne肌营养不良（BMD/DMD）患儿的临床表型与基因型的关联性，为疾病的管理、基因治疗及产前诊断提供理论依据。方法 回顾性分析52例患儿的临床资料及基因检测结果，对52例患儿均采用多重连接探针扩增（MLPA）的方法检测DMD基因，对MLPA检测未发现基因异常的患儿采用外显子芯片捕获结合高通量测序技术（NGS）进行筛查；并对20例先证者的母亲进行了测序验证。结果 结合MLPA和NGS测序技术检测到50例患儿携带BMD/DMD致病基因，检出率为96%。其中，基因缺失36例（69%）、重复7例（13%）、微小突变7例（13%）。在43例存在基因缺失/重复的患儿中，DMD 32例，BMD 11例；37例（86%）符合阅读框架原则，其中DMD 27例（96%），BMD 10例（67%）。7例微小突变均为DMD。结论 阅读框架原则对DMD有极高预测价值，对BMD预测有限。     

磁共振成像在肌营养不良疾病诊断中的应用价值

目的 总结肌营养不良(muscular dystrophy,MD)常见亚型下肢肌肉骨骼肌磁共振成像(magnetic resonance imaging,MRI)特点,积累应用MRI协助诊断MD的经验。方法 选取经基因检测确诊的48例MD患儿为研究对象,分析其下肢肌肉MRI特点,统计各亚型肌肉脂肪浸润累计评分,并分析Duchenne型肌营养不良脂肪浸润累计评分与临床指标的相关性。结果 Duchenne型肌营养不良以臀大肌、大收肌受累为著,Becker型肌营养不良以股外侧肌受累为著,肢带型肌营养不良以大收肌、股中间肌、股内侧肌、股外侧肌受累为著。Duchenne型肌营养不良下肢肌肉脂肪浸润累计评分与年龄、病程、肌肉力量及运动功能明显相关(P<0.05),与血清肌酸激酶无相关性(P>0.05)。结论 不同亚型MD的MRI表现特点不同,MRI有助于MD的诊断与病情评估。[中国当代儿科杂志,2022,24 (11):1231-1237]     

肌营养不良冷冻肌肉标本纤溶酶原激活物抑制物-1的表达

目的探讨纤溶酶原激活物抑制物-1(PAI-1)借助于抑制细胞外基质降解在进行性肌纤维化的发展中作用,揭示PAI-1在肌营养不良(MD)中的作用。方法应用免疫组织化学、双免疫荧光标记和Western印迹分析检测5例Duchenne型肌营养不良(DMD)、3例Becker型肌营养不良(BMD)、9例先天性肌营养不良(CMD)和4例正常活检冷冻肌肉标本中PAI-1的表达和细胞定位。结果PAI-1只在正常肌肉的血管内皮细胞处表达。免疫组织化学及Western印迹分析均表明PAI-1在大多数MD的萎缩肌肉中的表达明显高于正常肌肉。双免疫标记显示PAI-1在再生肌纤维的细胞浆和细胞核、巨噬细胞、巨噬细胞浸润的坏死纤维中强烈表达,在DMD和CMD肌肉中的肌内膜和肌束膜中的某些激活的成纤维细胞中明显表达。结论PAI-1在萎缩肌肉中过度表达的作用尚不清楚,但PAI-1在MD病变肌肉的局部表达增强及其明显的分布类型为PAI-1参与MD的病变提供了依据。     

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目的探讨金属蛋白酶组织抑制剂-1(TIMP-1)在进行性肌营养不良(PMD)发病中的作用。方法中国医科大学附属第一医院等单位于2002年4月至2003年3月,借助免疫组织化学、双免疫荧光标记和Western印迹分析的方法,检测Duchenne型肌营养不良(DMD)、Becker型肌营养不良(BMD)和先天性肌营养不良(CMD)患儿活检肌肉标本中TIMP-1的表达和细胞定位。结果免疫组织化学和双免疫荧光标记结果显示TIMP-1在正常肌肉的血管内皮细胞处表达;免疫组织化学和Western印迹分析均显示在PMD萎缩的肌肉中TIMP-1的表达明显增强;双免疫荧光标记进一步显示TIMP-1在再生肌肉纤维、巨噬细胞和巨噬细胞浸润的坏死纤维中明显表达,DMD和CMD肌肉中的肌内膜和肌束膜中某些激活的成纤维细胞也强烈表达TIMP-1。结论在PMD病变部位TIMP-1产生增多及其分布类型提示TIMP-1可能参与了PMD的发病。     

结缔组织生长因子在进行性肌营养不良中的表达

目的探讨结缔组织生长因子（CTGF）在进行性肌营养不良（PMD）中的作用。方法使用Duchenne型肌营养不良（DMD）8例、Becker型肌营养不良（BMD）2例、先天性肌营养不良（CMD）6例患儿的肌肉活检标本,借助免疫组织化学、双免疫荧光方法及Western印迹分析检测CTGF的免疫表达和定位。结果免疫组织化学和双免疫荧光法显示CTGF在正常肌肉的血管处明显表达;免疫组织化学法和Western印记分析均显示在PMD的萎缩肌肉中CTGF的免疫反应明显增强,所有病变肌肉组织中,CTGF在再生纤维的膜、胞浆及胞核中、巨噬细胞及巨噬细胞浸润的坏死纤维中强烈表达,也免疫定位在非再生纤维的肌纤维膜、肌内膜及肌束膜的结缔组织中;双免疫标记显示在肌内膜及肌束膜的大多数激活的成纤维细胞表达CTGF;但年长的CMD患儿的晚期纤维化中CTGF弱表达或无表达。结论结果表明CTGF可能参与了PMD的发病过程,肌肉内的CTGF可能在肌纤维再生和肌肉纤维化的病变过程中起重要作用。     

症状前期进行性肌营养不良患儿24例病例系列报告

背景：进行性肌营养不良（PMD）中Duchenne型肌营养不良(DMD)和Becker型肌营养不良(BMD)的临床表现、治疗和预后差异明显,目前国内外对症状前期PMD患儿的诊断尚无共识。 目的：探讨婴幼儿时期症状前期PMD患儿的临床特征和实验室检查特点,并探讨血清肌酶水平在DMD和BMD分型诊断中的价值。 设计：病例系列报告。 方法：收集2016年1月至2020年7月江西省儿童医院确诊的症状前期PMD患儿,分析临床特征和实验室检查特点,并以基因检测结果为诊断标准分为DMD组和BMD组,血清肌酶通过ROC曲线分析以约登指数最大值时的取值作为诊断界值,比较不同肌酶的诊断准确性。 主要结局指标：PMD患儿的临床表现、基因结果、血清酶水平（AST、ALT、LTH、CK、CK-MB）。 结果：24例PMD患儿纳入分析,其中DMD组18例,BMD组6例。22例（91.7%）因发现转氨酶升高就诊,2例（8.3%）因亲戚确诊前来就医。PMD患儿CK-MB、CK、LDH、AST和ALT水平均明显升高,DMD组均高于BMD组（除AST外,P均<0.05）。当ALT>224.5 U·L-1、CK>11 069 IU·L-1、CK-Mb>204 IU·L-1、LDH>1 349.5 IU·L-1时为DMD的可能性更高,尤其是LDH>1 349.5 IU·L-1具有高度特异性。 结论：血清肌酶水平增高为 PMD 患儿症状前期的主要表现。LDH＞1 349.5 IU·L-1对诊断DMD具有高度特异性。     

Classic manifestations of Duchenne dystrophy in a young female patient: A case report

Duchenne and Becker muscular dystrophies (DMD/DMB) are neuromuscular diseases linked to chromosome X and affect mainly male individuals. Duchenne muscular dystrophy is the most severe form of the disease, leading to a decreased patient survival compared with individuals with Becker type and female carriers of the mutated gene.In this paper we present the case of a female adolescent whose clinical picture and disease course closely resembled male individuals.     

Duchenne Muscular Dystrophy: A Practice Update

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive disorder caused by a deficient or defective synthesis of dystrophin protein. DMD is the most common form of muscular dystrophy with an incidence of about 1 in 5000 live boys. Though primarily resulting in progressive muscle weakness, it affects various other organs as well. Heart, brain and smooth muscles are commonly involved, because of expression of dystrophin in these organs. The management of DMD requires a multidisciplinary liaison, anticipatory management and prevention of the complications. Consensus based international recommendation for management of DMD have been published in the year 2010, recognizing DMD as a multi-systemic and progressive disease. The proper management of a boy with DMD can improve ambulation, independence, quality of life and delay disease – related complications. A lot can be done to comfort affected children and their care givers even in a resource limited setting. This review discusses these options and also the current understanding of the disease.     

杜兴型肌营养不良50例临床及病理分析

目的：总结分析杜兴型肌营养不良（Duchenne muscular dystrophy, DMD）患儿的临床及病理特点,旨在加强对DMD的认识,提高DMD的早期诊断率。方法：对50例通过临床表现、骨骼肌活检并进行单克隆抗体免疫组化染色确诊的DMD患儿的临床资料进行回顾性分析。结果：DMD患儿临床表现为：自幼跑步慢,爬楼、蹲起费力,逐渐出现走路姿势异常,检查发现肌酸激酶显著增高,肌电图呈肌源性损害。组织化学染色显示：50例患儿苏木精-伊红染色均可见肌纤维大小不一,圆形化,肌纤维明显变性、坏死,肌纤维不同程度再生,结缔组织增生;部分肌纤维间可见少量炎性细胞浸润。免疫组织化学染色显示：50例患儿均可见肌纤维膜dystrophins蛋白表达完全缺失,33例患儿肌纤维膜sarcoglycans（-α,-β,-γ,-δ）不同程度表达减弱。结论：对具有上述临床表现的患儿,建议行骨骼肌活检并进行单克隆抗体免疫组化染色,发现肌细胞膜上dystrophins蛋白缺失即可确诊DMD。     

杜氏肌营养不良患者心脏损害的研究进展

杜氏肌营养不良是儿童致死性肌萎缩性疾病。该疾病发病率低、进展迅速、医生认识有限以及呼吸衰竭的有效治疗等多种因素,使心力衰竭成为杜氏肌营养不良患者死亡的首要原因。早期发现、诊治杜氏肌营养不良患者的心脏损害,对于延长患者生存时间和改善生活质量具有重要意义。该文就近年来杜氏肌营养不良患者心脏损害的流行病学、发病机制、早期诊断技术、预防和治疗等方面的研究进展作一综述。     

Knee-ankle-foot orthosis in children with duchenne muscular dystrophy: user views and adjustment.

BACKGROUND: The use of knee ankle foot orthoses (KAFOs) to prolong independent mobility is a widely used rehabilitation strategy for children with Duchenne muscular dystrophy (DMD). AIMS: To explore views and adjustment of families with a child with Duchenne muscular dystrophy to the use of KAFOs. METHODS: interviews with families of children aged 8-18 years with DMD; questionnaires on psychiatric adjustment (SDQ for children; GHQ for parents). RESULTS: In total, 17 parents and 9 children took part. Families experienced the introduction of KAFOs as a signal for illness deterioration and a re-awakening of the feelings experienced at diagnosis. Nevertheless, the majority expressed a positive attitude and over two-thirds satisfaction with KAFOs use. High psychiatric risk was found in 2/17 children (12%; expected 10%) and 7/17 main carers (41%; expected 20-30%). CONCLUSION: Most families were satisfied with KAFOs use, and its implementation was well tolerated especially by the children. However, mental distress was high in main carers who emphasized the importance of full preparation and support in this rehabilitation technique.     

Duchenne's muscular dystrophy in monozygotic twins

The rare occurrence of Duchenne's muscular dystrophy (DMD) in a twin pair is documented. The observation of concordance for muscular dystrophy in the monozygotic (MZ) twin pair in an otherwise normal family helps to verify the genetic causation of sporadic, cases of the disease.