The resistive range of motion exercise training in Duchenne muscular dystrophy:a case study

Background:To determine the effectiveness of resistive range of motion exercises in improving muscle strength and functional abilities in Duchenne muscular dystrophy.The study was also aimed to determine if resistive range of motion exercises can slow down the progression of the disease.Methods:A seven-year-old male child was diagnosed with Duchenne muscle dystrophy presented to outpatient physiotherapy clinic.The patient was presented with difficulty in stair climbing,sitting up from the floor,fatigue,and muscle weakness specifically weakness in the proximal limb muscles.The progressive resistive range of motion training was implemented for four years to improve muscle strength and functional abilities.The medical research council grading scale,north ambulatory assessment scale,and creatine kinase were used to evaluate muscle strength,functional abilities,and creatine kinase levels.Results:The muscular strength and functional abilities did not improve after four years of exercise training.The creatine kinase levels were decreased over the period of four years.Conclusion:Resistive range of motion exercises are helpful in maintaining the muscular strength and functional abilities in Duchenne muscular dystrophy.

Surgical and long-term functional outcomes of patients with Duchenne muscular dystrophy following spinal deformity correction

BACKGROUND Life expectancy in patients with Duchenne muscular dystrophy(DMD)has improved due to advances in medical care.DMD patients develop progressive spinal deformity after loss of ambulatory function and onset of wheelchair dependence for mobility.There is limited published data on the effect of spinal deformity correction on long-term functional outcomes,quality of life(QoL),and satisfaction in DMD patients.AIM To investigate the long-term functional outcomes following spinal deformity correction in DMD patients.METHODS This was a retrospective cohort study from 2000-2022.Data was collected from hospital records and radiographs.At follow-up,patients completed the muscular dystrophy spine questionnaire(MDSQ).Statistical analysis was performed by linear regression analysis and ANOVA to analyse clinical and radiographic factors significantly associated with MDSQ scores.RESULTS Forty-three patients were included with mean age 14.4 years at surgery.Spinopelvic fusion was performed in 41.9%of patients.Mean surgical time was 352.1 min and mean blood loss was 36%of estimated total blood volume.Mean hospital stay was 14.1 d.Postoperative complications occurred in 25.6%of patients.Mean preoperative scoliosis was 58°,pelvic obliquity 16.4°,thoracic kyphosis 55.8°,lumbar lordosis 11.1°,coronal balance 3.8 cm,and sagittal balance+6.1 cm.Mean surgical correction of scoliosis was 79.2%and of pelvic obliquity was 80.8%.Mean follow-up was 10.9 years(range:2-22.5).Twenty-four patients had died at follow-up.Sixteen patients completed the MDSQ at mean age 25.4 years(range 15.2-37.3).Two patients were bed-ridden and 7 were on ventilatory support.Mean MDSQ total score was 38.1.All 16 patients were satisfied with the results of spinal surgery and would choose surgery again if offered.Most patients(87.5%)reported no severe back pain at follow-up.Factors significantly associated with functional outcomes(MDSQ total score)included greater duration of post-operative follow-up,age,scoliosis postoperatively,correction of scoliosis,increased lumbar lordosis postoperatively,and greater age at loss of independent ambulation.CONCLUSION Spinal deformity correction in DMD patients leads to positive long-term effects on QoL and high patient satisfaction.These results support spinal deformity correction to improve long-term QoL in DMD patients.

Tetramethylpyrazine Nitrone Improved Motor Deficits and Alleviated Dystrophic Muscle Pathology in the <i>mdx</i>Mouse Model of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive neuromuscular disorder caused by mutations in the dystrophin encoding gene, with the characteristics of a severe and progressive destruction of muscle structure and function. Skeletal muscle fibrosis is one of the pathological features of DMD. Tetramethylpyrazine (2,3,5,6-tetramethylpyrazine, TMP) has been demonstrated to reduce heart and liver fibrosis. Meanwhile, previous studies showed that Tetramethylpyrazine nitrone (TBN), a nitrone derivative of TMP, has promising therapeutic effects in several neurodegenerative models and is more potent than TMP. In this study, we investigated the potential effect of TBN on the mdx mouse model of DMD. Eight-week-old mdx mice were administered with TBN (30 mg/kg) intragastrically twice daily, with deflazacort (1 mg/kg) once a day as a positive control, for a total of 24 weeks. Behavioral tests including pole-climbing open-field test were monitored every 4 weeks. Histopathological assessment was conducted in the gastrocnemius and diaphragm muscles. The effects of TBN on protein levels of dysferlin were measured by immunohistochemistry. TBN significantly reduced the climbing time in pole test and increased the total distance moved in an open-field test of mdx mice. TBN attenuated fibrosis in the gastrocnemius and diaphragmatic muscles. In addition, TBN protected gastrocnemius muscle fibers via increasing expression of the dysferlin in mdx mice. In conclusion, this study demonstrated that TBN could improve the motor deficits and muscle pathology of mdx mouse, and it is worth further exploring the mechanism of action of TBN for DMD treatment.

Stem cell transplantation for treating Duchenne muscular dystrophy A Web of Science-based literature analysis

OBJECTIVE： To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science. DATA RETRIEVAL： We performed a bibliometric analysis of studies on stem cell transplantation for treating Duchenne muscular dystrophy from 2002 to 2011 retrieved from Web of Science. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed published articles on stem cell transplantation for treating Duchenne muscular dystrophy indexed in Web of Science; （b） original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and （c） publication between 2002 and 2011. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） documents that were not published in the public domain; and （c） corrected papers. MAIN OUTCOME MEASURES： （1）Annual publication output; （2） distribution according to subject areas; （3） distribution according to journals; （4） distribution according to country; （5） distribution according to institution; （6） distribution according to institution in China; （7） distribution according to institution that cooperated with Chinese institutions; （8） top-cited articles from 2002 to 2006; （9） top-cited articles from 2007 to 2011. RESULTS： A total of 318 publications on stem cell transplantation for treating Duchenne muscular dystrophy were retrieved from Web of Science from 2002 to 2011, of which almost half derived from American authors and institutes. The number of publications has gradually increased over the past 10 years. Most papers appeared in journals with a focus on gene and molecular research, such as Molecular Therapy, Neuromuscular Disorders, and PLoS One. The 10 most-cited papers from 2002 to 2006 were mostly about different kinds of stem cell transplantation for muscle regeneration, while the 10 most-cited papers from 2007 to 2011 were mostly about new techniques of stem cell transplantation for treating Duchenne muscular dystrophy. CONCLUSION： The publications on stem cell transplantation for treating Duchenne muscular dystrophy were relatively few. It also needs more research to confirm that stem cell therapy is a reliable treatment for Duchenne muscular dystrophy.

Immunadsorption therapy for end stage heart failure due to Duchenne muscular dystrophy

We report about a successful immunadsorption therapy of a boy with end stage heart failure due to Duchenne muscular dystrophy who has little chance to get cardiac transplantation. Prior to this therapy a medical therapy with an angiotensin converting enzyme inhibitor, a low dose betablocker, an aldosterone antagonist, and diuretics failed. In consent with the patient and his parents immunoadsorption therapy employing a protein A column was performed. Due to clinical improvement the betablocker carvedilol could be titrated from 6.25 mg up to 30 mg. In the following 4 month he improves from NYHA class IV to NYHA class II and NT-Pro-BNP levels fell from 5180 pg/ml to 402 pg/ml. The mean heart rate in Holter ECG decreases from 102/min to 68/min and ejection fraction improved from 25% to 30%. The boy began to walk without any support and was able to visit school. This clinical improvement now holds on for 2 years.

Umbilical cord mesenchymal stem cell transplantation for the treatment of Duchenne muscular dystrophy

Due to their relative abundance,stable biological properties and excellent reproductive activity,umbilical cord mesenchymal stem cells have previously been utilized for the treatment of Duchenne muscular dystrophy,which is a muscular atrophy disease.Three patients who were clinically and pathologically diagnosed with Duchenne muscular dystrophy were transplanted with umbilical cord mesenchymal stem cells by intravenous infusion,in combination with multi-point intramuscular injection.They were followed up for 12 months after cell transplantation.Results showed that clinical symptoms significantly improved,daily living activity and muscle strength were enhanced,the sero-enzyme,electromyogram,and MRI scans showed improvement,and dystrophin was expressed in the muscle cell membrane.Hematoxylin-eosin staining of a muscle biopsy revealed that muscle fibers were well arranged,fibrous degeneration was alleviated,and fat infiltration was improved.These pieces of evidence suggest that umbilical cord mesenchymal stem cell transplantation can be considered as a new regimen for Duchenne muscular dystrophy.

Myocardial Protection with Beta Blocker Treatment in Infants with Heart Failure Due to Congenital Heart Defects and Duchenne Muscular Dystrophy

Our first intention to treat infants’ heart failure with beta blockers was to improve the clinical condition as shown in our prospective randomized trial. We only use non-selective beta blockers in these infants, carvedilol in those with left ventricular dysfunction and propranolol in those with congenital heart disease without ventricular dysfunction. Despite a significant improvement of Ross’s heart failure score, we could not convince most colleagues within the last 25 years if the concept of neurohumoral activation in heart failure is not well-established pediatric cardiology. Recently, Honghai Liu et al. published that cardiomyocyte cytokinesis failure was increased in congenital heart disease. Inactivation of the beta adreno receptors genes and administration of the beta-blocker propranolol increased cardiomyocyte division in neonatal mice, which increased the number of cardiomyocytes (endowment) and conferred benefit after myocardial infarction in adults. We currently realize that propranolol in infants with congenital heart disease not only decrease highly elevated NT-Pro-BNP values but also decrease cardiac troponin T values that may indicate myocardial injury due to neurohumoral activation. We reproduce this observation, primarily seen in infants with congenital heart disease, in an infant with Duchenne muscular dystrophy. These observations were in good accordance with current data from H. Liu et al., who showed that treatment with non-selective beta blockers early after birth might rescue cytokinesis defects and prevent heart dysfunction in adulthood in a mouse model.

Ventilation function changes in patients with Duchenne muscular dystrophy under and over 12 years of age Analysis of 65 cases

BACKGROUND：Previous studies indicate that vital capacity in patients with Duchenne muscular dystrophy increases with age when they are under 12 years old, and decreases from 13 or 14 years of age; however, recent studies indicate that the vital capacity in patients with Duchenne muscular dystrophy begins to decrease even before 12 years of age. OBJECTIVE： To verify if the vital capacity in patients with Duchenne muscular dystrophy decreases before the age of 12 years and to observe the effect of rehabilitation exercise on vital capacity. DESIGN, TIME AND SETTING： The case analysis was performed at the Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University （Guangzhou, Guangdong Province, China） from December 2004 to January 2006. PARTICIPANTS： Sixty-five male patients diagnosed as having Duchenne muscular dystrophy and who underwent pulmonary ventilation function examination at the Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University （Guangzhou, Guangdong Province, China） from December 2004 to January 2006; ages ranged from 6 to 22 years old. METHODS： The ventilation function of 65 patients was determined using a Sensor Medics 2100 pulmonary function test apparatus （USA）, and the data obtained were subjected to statistical analysis comparing patients under 12 years of age and those above 13 years of age, and comparing those who performed rehabilitation exercise with those who did not. MAIN OUTCOME MEASURES： Forced vital capacity （FVC）; forced expiratory volume in one second （FEV1）; maximal voluntary ventilation （MMV）; the ratio of forced expiratory volume in one second and forced vital capacity （FEV1/FVC）; each measured value as a percentage of the corresponding predicted value. RESULTS： There were no significant differences in FVC, FEV1 and MMV between patients under 12 years of age and those above 13 years of age （P 〉 0.05）. The FVC, FEV1 and MMV values, as percentages of the predicted values, were, in patients under 12 years old, significantly higher than those in patients older than 13 （P 〈 0.05）. All ventilation function parameters except FEV1/FVC in patients undergoing rehabilitation exercise were higher than those in patients without rehabilitation exercise. This difference was not significant in patients under 12 years of age, but was statistically significant in those older than 13 years （P 〈 0.05）. CONCLUSION： Although the values of ventilation function measured increase with age in Duchenne muscular dystrophy patients less than 12 years of age, real ventilation function is already damaged. Thirteen years of age is an important time point for pulmonary function change. Rehabilitation exercise can slow down the process of pulmonary function exacerbation in Duchenne muscular dystrophy patients, especially when therapy starts before 12 years of age.

优化多重PCR检测Duchenne muscular dystrophy基因外显

目的:介绍一种快速简便地优化多重PCR检测DMD基因外显子缺失的方法及详细步骤.方法:采2ml外周血,用0.2%氯化钠处理收集白细胞,再用基因组DNA提取试剂盒抽提基因组DNA,用优化的多重PCR法直接检测DMD基因外显子的缺失.结果:用该方法检测DMD基因外显子缺失结果准确清晰.结论:用优化的多重PCR技术可以直接检测DMD基因外显子缺失,跟通常使用的9对引物一步法相比,具有经济、快速、简便等特点.

THE MECHANISM OF CEREBRAL EVOKED POTENTIALS BY REPETITIVE MAGNETIC STIMULATION OF GASTROCNEMIUS MUSCLE IN DUCHENNE MUSCULAR DYSTROPHY

Objective. To study the features and mechanism of the cerebral evoked potentials by repetitive stimulation of calf muscle in Duchenne muscular dystrophy (DMD) patients with obvious muscular dystrophy and psuedohypertrophy. Methods. Cerebral evoked potentials by stimulation of calf muscles and somatosensory evoked potentials (SEPs) by the stimulation of posterior tibial nerves at ankle were measured in 10 patients with DMD and 10 normal controls matched with gender and age. The intensity of the magnetic stimulation was at 30％ of maximal output (2.1 Tesla, MagPro magnetic stimulator, Dantec) and the frequency was 1 Hz. The low intensity of magnetic stimulation was just sufficient to produce a contraction of the muscle belly underneath the coil. Recording electrode was placed at 2 cm posterior to the Cz, reference to Fpz. The latencies of N33, P38, N48 and P55 and amplitude (P38－ N48) were recorded. SEPs were recorded by routine methods. Results. In normal subjects, the amplitudes of cerebral evoked potentials by magnetic stimulation of calf muscle was 40％ lower than that by electrical stimulation of the posterior tibial nerves at ankle. The latency of P38 was 2.9± 2.1 ms longer compared with electrical stimulation of the posterior tibial nerves at ankle. In 6 patients, P38 latency from magnetic stimulation was remarkably prolonged (P< 0.01), and in 4 patients, there was no remarkable response. SEPs evoked by electrical stimulation were normal in all of the patients. Conclusion. DMD is an available model for the study of mechanism of cerebral evoked potentials by magnetic stimulating muscle. We can conclude that the responses from magnetic stimulation were produced by muscle input. The abnormal responses in patients may relate to decreased input of muscle by stimulating dystrophic and psedohypertrophic muscle.

T2 Mapping and Fat Quantification of Thigh Muscles in Children with Duchenne Muscular Dystrophy

Quantitative magnetic resonance image(MRI)in individual muscles may be useful for monitoring disease progression in Duchenne muscular dystrophy(DMD).The purpose of this study w批to measure丁2 relaxation time of thigh muscles in children with DMD and healthy boys,and to correlate the T2 relaxation time of muscles with the fat fraction(FF)at quantitative magnetic resonance and results of clinical assessment.Thirty-two boys with DMD and 18 healthy boys were evaluated with T2 mapping and three-point Dixon MRI.Age,body mass index(BMI),muscle strength assessment,timed functional tests(time to walk or run 10 metres,rise from the floor and ascend four stairs),and the North Star Ambulatory Assessment(NSAA)were evaluated.Spearman’s correlation was used to assess the relationships between FF and clinical assessments and T2 relaxation time.The mean T2 relaxation time of thigh muscles in DMD was significantly longer than that in the control group(P<0.05),except for the gracilis(P=0.952).The gracilis,sartorius and adductor longus were relatively spared by fatty infiltration in DMD patients.The T2 relaxation time was correlated significantly with the mean FF in all muscles.Age,BMI,total muscle strength score,timed functional tests and NSAA were significantly correlated with the overall mean T2 relaxation time.T2 mapping may prove clinically useful in monitoring muscle changes as a result of the disease process and in predicting the outcome of DMD patients.

Recurrent hypotension induced by sacubitril/valsartan in cardiomyopathy secondary to Duchenne muscular dystrophy: A case report

BACKGROUND Duchenne muscular dystrophy(DMD),which is caused by a mutation/deletion in the dystrophin gene on the X-chromosome,is the most common type of neuromuscular disorder in pediatrics.Skeletal muscle weakness progressively develops in DMD patients and usually leads to respiratory failure in the early adolescent years.Cardiac muscle is frequently affected in DMD patients,which leads to a high burden of cardiomyopathy and heart failure.In the era of improved respiratory care,cardiac deaths are becoming the major cause of mortality in DMD patients.CASE SUMMARY We report the case of a 15-year-old boy who presented to the hospital due to recurrent orthopnea for 6 mo and palpitations for 4 mo.He was diagnosed with progressive muscular dystrophy at the age of 3 years and was confined to a wheelchair at 12 years.He was prescribed diuretics and digoxin at the outpatient clinic;however,his symptoms did not resolve.Sacubitril/valsartan was added 1 mo prior to presentation,but he experienced recurrent episodes of palpitations.The electrocardiogram showed atrial tachycardia with a heart rate of 201 bpm,and he was then hospitalized.Hypotension was found following the administration of sacubitril/valsartan tablets;he could not tolerate even a small dose,always developing tachyarrhythmia.His symptoms were relieved after discontinuing sacubitril/valsartan,and his heart rate was controlled by a small dose of metoprolol tartrate and digoxin.Atrial tachycardia spontaneously converted in this patient,and his symptoms attenuated in the following 6 mo,without palpitation episodes.CONCLUSION Blood pressure should be closely monitored in DMD patients with advanced heart failure when taking sacubitril/valsartan.

Role of Complements and Immunoglobulins in Duchenne Muscular Dystrophy

Muscular dystrophies are myopathies and tend to progressive, with ongoing degeneration and regeneration of muscle fibers. Spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and polio myelitis are essentially diseases of the anterior horn cells of the spine. It has been reported in literature that humoral immunity is manifested by the antibodies production. These are special chemical substances that react against foreign body. Antibodies are serum proteins, which are immunoglobulins and possess antibody activity and are classified according to antigens and stimulate their production such as IgA, JgG, IgM, IgD and IgE. All the immunological parameters such as of C3, C4, IgG, IgM and IgA, which are measured in Duchenne muscular dystrophy go down in comparison to healthy subjects. Complement C3 and Complement C4 go down about 44.3% and 78.57% respectively from the normal values. The serum IgG, IgM and IgA levels were also go down about 65%, 84% and 99.56% respectively in comparison to healthy subjects. A trend between all the immunoglobulins has been set up and it is rAG.M > rMA.G. > rGM.A, while we have a trend in DMD cases is rMA.G. > rAG.M > rGM.A We are in a position to say that our data have a relevance of high authenticity and reliability to accept that there is a deficit in immunity in DMD cases. The deficit in immunity may be a cause to damage muscle for abnormal functioning.

Decreased Gait and Function in Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a genetic disorder linked to chromosome Xp21, due to absence of dystrophin production. It is clinically characterized by progressive muscle weakness, fatigue, and development of joint contractures that compromise general motor functionality, mainly the gait. Objective: To characterize the motor function and decrease gait in children with DMD using the Portuguese version of the Motor Function Measure scale (MFM-P). Methods: A review of medical records including chronological age and scores from MFM-P of children with a DMD who attended at the Neuromuscular Diseases Clinic at Campinas State University (UNICAMP), Brazil was performed in this study. A total of 36 medical records of male patients with confirmed clinical diagnosis of DMD, ambulatory or not, regardless of age;excluding those with other associated diseases or other types of muscular dystrophies were selected. Data were analyzed using Kolmogorov-Smirnov and Spearman correlation statistical tests. Results: Analysis of all data collected showed that 75% of our sample had D1 scores lower than 41.02%. There was a linear relationship between the scores of D2 and D3, but no association between D2 and D1 scores was noted. D1 score was between 40% and 80% in those patients presenting D2 scores between 80% and 100%. In all cases patients with low total score presented a greater risk for loss of gait and their functionality. Conclusion: The standing posture and the postural transfers were the worst activities observed in children with DMD, with positive correlation between proximal and distal motor function. Even with high scores according MFM-P in proximal function, the children showed strong predictors for loss of gait.

Adipose-derived stem cells enhance myogenic differentiation in the mdx mouse model of muscular dystrophy via paracrine signaling

Adipose-derived stem cells have been shown to promote peripheral nerve regeneration through the paracrine secretion of neurotrophic factors. However, it is unclear whether these cells can promote myogenic differentiation in muscular dystrophy. Adipose-derived stem cells （6 × 106） were injected into the gastrocnemius muscle of mdx mice at various sites. Dystrophin expression was found in the muscle fibers. Phosphorylation levels of Akt, mammalian target of rapamycin （mTOR）, eIF-4E binding protein 1 and $6 kinase 1 were increased, and the Akt/mTOR pathway was activated. Simultaneously, myogenin levels were increased, whereas cleaved caspase 3 and vimentin levels were decreased. Necrosis and fibrosis were reduced in the muscle fibers. These findings suggest that adipose-derived stem cells promote the re- generation and survival of muscle cells by inhibiting apoptosis and fibrosis, thereby alleviating muscle damage in muscular dystrophy.

Promising therapeutic approaches of utrophin replacing dystrophin in the treatment of Duchenne muscular dystrophy

Duchenne muscular dystrophy(DMD)is a serious genetic neuromuscular rare disease that is prevalent and caused by the mutation/deletion of the X-linked DMD gene that encodes dystrophin.Utrophin is a dystrophin homologous protein on human chromosome 6.Dystrophin and utrophin are highly homologous.They can recruit many dystrophin-glycoprotein complex(DGC)-related proteins and co-localize at the sarcolemma in the early stage of human embryonic development.Moreover,utrophin is overexpressed naturally at the mature myofiber sarcolemma in DMD patients.Therefore,utrophin is considered the most promising homologous protein to replace dystrophin.This review summarizes various modulating drugs and gene therapy approaches for utrophin replacement.As a universal method to treat DMD disease,utrophin has a promising therapeutic prospect and deserves further investigation.

A different spectrum of DMD gene mutations in local Chinese patients with Duchenne/Becker muscular dystrophy

Background Duchenne muscular dystrophy （DMD） and Becker muscular dystrophy （BMD） are X-linked recessive, allelic disorders. This study was conducted to look into the spectrum of DMD gene mutations in Hong Kong Chinese patients with Duchenne or Becker muscular dystrophy （DMD/BMD）, and to study genotype-phenotype correlation.

骨骼肌MRI成像在Duchenne肌营养不良症的应用价值

目的分析骨骼肌磁共振成像(MRI)成像技术在Duchenne型肌营养不良症(DMD)的临床应用价值。方法收集2019年5月至2022年5月在本院收治的64例DMD患者临床资料(DMD组),另选取本院无神经肌肉障碍及肌无力病史的16例正常健康体检男孩进行MRI骨骼肌成像检查(对照组)。入试者均行T_(1)WI肌肉冠状面扫描、横断面T_(1)WI和T_(2)WI-STIR脂肪抑制序列检查,观察所得MRI图像,分析肌肉脂肪浸润和水肿特点,对比不同人群、不同临床特征患者中MRI脂肪浸润、水肿累计评分差异,分析MRI脂肪浸润、水肿累计评分与患者临床特征相关性。结果DMD患者T_(1)WI和T_(2)WI-STIR脂肪检查中受累肌肉的变性均为高信号,提示正常的肌肉组织为脂肪组织浸润替代;对照组MRI检查为中等强度信号。64例DMD患者大腿肌肉均出现不同程度脂肪浸润情况,以臀大肌受累最明显(100%),股薄肌受累最少(39.06%);T_(1)WI脂肪浸润评分为4分最高为臀大肌(62.50%),最低为缝匠肌与股薄肌;T_(1)WI脂肪浸润评分为0分者占比最高为股薄肌(60.94%),其次为缝匠肌(56.25%)。51例患者大腿肌肉出现不同程度水肿改变,累频率低于脂肪浸润受累频,表现为双侧不对称性分布,以股二头肌受累最明显(64.06%),最少受累为阔筋膜张肌(20.31%);T_(2)WI-STIR水肿分级为3级最高者为肌肉为半腱肌(17.19%),分级为0级最多为阔筋膜张肌(79.69%)。DMD组MRI脂肪浸润、水肿累计评分均明显高于对照组(P<0.05)。不同年龄、身高、体重、临床运动功能分级的DMD组患者中的MRI脂肪浸润评分比较存在差异(P<0.05),Pearson相关性结果显示MRI脂肪浸润与患者年龄、身高、体重、临床运动功能之间均存在正相关关系(P<0.05),与BMI之间无相关性(P>0.05);水肿评分与DMD患者各项临床特征无相关性(P>0.05)。结论DMD患者骨骼肌MRI成像具有一定特征性,MRI脂肪浸润评分可反映肌肉受累情况及程度,且与患者临床运动功能密切相关,对临床诊疗及疾病严重程度评估有参考价值。

Lama1 upregulation prolongs the lifespan of the dy^(H)/dy^(H) mouse model of LAMA2-related congenital muscular dystrophy

LAMA2-related congenital muscular dystrophy(LAMA2-CMD),characterized by laminin-α2 deficiency,is debilitating and ultimately fatal.To date,no effective therapy has been clinically available.Laminin-a1,which shares significant similarities with laminin-a2,has been proven as a viable compensatory modifier.To evaluate its clinical applicability,we establish a Lama2 exon-3-deletion mouse model(dy^(H)/dy^(H)).The dy^(H)/dy^(H) mice exhibit early lethality and typical LAMA2-CMD phenotypes,allowing the evaluation of various endpoints.In dy^(H)/dy^(H) mice treated with synergistic activation mediator-based CRISPRa-mediated Lama1 upregulation,a nearly doubled median survival is observed,as well as improvements in weight and grip.Significant therapeutical effects are revealed by MRl,serum biochemical indices,and muscle pathology studies.Treating LAMA2-CMD with LAMA1 upregulation is feasible,and early intervention can alleviate symptoms and extend lifespan.Additionally,we reveal the limitations of LAMA1 upregulation,including high-dose mortality and non-sustained expression,which require further optimization in future studies.

社会工作视角下Duchenne型肌营养不良病人家庭困境研究进展与对策

从诊疗、康复、心理、教育、经济5个方面分析Duchenne型肌营养不良病人家庭面临的困境,提出提供社会支持,增强病人家庭应对能力,倡导政策支持,完善Duchenne型肌营养不良病人家庭社会保障体系的对策,以期进一步推进Duchenne型肌营养不良的研究和治疗工作。