The mechanisms and treatments of muscular pathological changes in immobilization-induced joint contracture: A literature review / 中华创伤杂志(英文版)

The clinical treatment of joint contracture due to immobilization remains difficult. The pathological changes of muscle tissue caused by immobilization-induced joint contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis. The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway, caspase system pathway, matrix metalloproteinase pathway, Ca-dependent pathway and autophagy-lysosomal pathway. The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-β1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α. This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle contracture and the currently available treatments. Understanding the mechanisms involved in immobilization-induced contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future.

The relationship between muscle fibrosis and the hyoid displacement in dysphagic patients with nasopharyngeal carcinoma after radiation therapy / 中华物理医学与康复杂志

Objective To evaluate the relationship between muscle fibrosis and the displacement of the hyoid bone while swallowing among patients with nasopharyngeal carcinoma (NPC) after radiation therapy.Methods Twenty-six NPC patients with dysphagia were recruited.Shear wave elastography was performed to assess the fibrosis of the mylohyoid muscle.The horizontal and vertical displacement of the hyoid bone were measured based on the videofluoroscopic swallowing study,and the severity of dysphagia was determined using the penetration-aspiration scale (PAS).The correlation between the modulus value of the mylohyoid muscle and the horizontal and vertical displacement of the hyoid bone were analyzed,respectively.Receiver-operating characteristic (ROC) curve were constructed to assess the diagnostic ability of modulus value for the severity of dysphagia above grade 5 of PAS.Results For patients whose PAS was higher than grade 5,the modulus value of mylohyoid muscle was negatively correlated with the displacement of hyoid bone,while such correlation was absent for patients whose PAS grading were less than or equal to 5.Sensitivity and specificity by modulus value to detect dysphagia were 80％ and 81.8％,respectively,with the best cut-off value of 14.37 kPa.Conclusion The reduction of hyoid bone displacement can be partially attributed to muscle fibrosis for post-radiation NPC patients with severe dysphagia.The modulus value measured by Shear wave elastography could be used as a supplementary way to monitor the development of dysphagia.

Fibrosis in Skeletal Muscle: Celluar and Molecular Mechanism (review) / 中国康复理论与实践

@#Skeletal muscle has high regenerative capability. It is able to regenerate completely after acute traumatic damage, while the repairing process often accompanied by fibrosis in the chronic degenerative conditions such as muscular dystrophy and repeated muscle fiber damage. Through in-depth study on the mechanisms of skeletal muscle fibrosis in the past decade, it has been found that a variety of cells and regulatory molecules involved in the process, especially muscle satellite cells-derived myofibroblasts, transforming growth factor β (TGF-β) and other fibrosis promoting growth factors. This review focused on the cellular and molecular mechanisms of the skeletal muscle fibrosis and relevant antagonistic strategies.

Role of Transforming Growth Factor-β1 in the Process of Fibrosis of Denervated Skeletal Muscle / 华中科技大学学报（医学）（英德文版）

In order to investigate the biological function of transforming growth factor-β1 (TGF-β1)during fibrosis in denervated skeletal muscle,we recruited sciatic nerve injury model of SD rats in which denervated gastrocnemius was isolated for analysis.At different time points after operation,denervated muscle was examined by several methods.Masson trichrome staining showed morphological changes of denervated skeletal muscle.Quantitative RT-PCR detected the rapid increase of TGF-β1 expression at mRNA level after nerve injury.It was found that a peak of TGF-β1 mRNA expression appeared one week post-operation.The expression of collagen Ⅰ (COL Ⅰ ) mRNA was up-regulated in the nerve injury model as well,and reached highest level two weeks post-injury.Immunoblot revealed similar expression pattern of TGF-β1 and COL Ⅰ in denervated muscles at protein level.In addition,we found that the area of the gastrocnemius muscle fiber was decreased gradually along with increased interstitital fibrosis.Interestingly,this pathological change could be prevented,at least partly,by local injection of TGF-β1 antibodies,which could be contributed to the reduced production of COL Ⅰ by inhibiting function of TGF-β1.Taken together,in this study,we demonstrated that the expression of TGF-β1 was increased significantly in denervated skeletal muscle,which might play a crucial role during muscle fibrosis after nerve transection.

Alteraciones del sistema nervioso central asociadas a fibrosis congénita de músculos extraoculares / Central nervous system abnormalities related to congenital fibrosis of extraocular muscles

Objetivo: Describir las alteraciones del sistema nervioso central asociadas a dismorfogenesias de los nervios craneales. Material y métodos: Estudio retrospectivo, observacional, transversal y descriptivo de pacientes con estrabismo por fibrosis congénita de los músculos extraoculares, atendidos entre enero de 2001 y enero de 2006. Fueron identificadas las lesiones neurológicas y se analizó su asociación. Resultados: Todos los pacientes tuvieron estrabismos fibróticos. Se incluyeron 16 pacientes, nueve hombres y siete mujeres. Las lesiones neurológicas asociadas fueron anomalías de cuerpo calloso, cortipatía severa con sordera, epilepsia, cavum vergae, nistagmo, quiste subaracnoideo occipital e hidrocefalia. Se demostró retraso psicomotor en 56 % de los pacientes. Se identificaron malformaciones congénitas como trigonocefalia, camptodactilia, hipoplasia facial, implantación baja de orejas. La ptosis palpebral se encontró en 81 % de los casos. El estrabismo más frecuente fue la exotropía (56 %) seguida de hipotropía (37.5 %), hipertropía (18.7 %), anisotropía en “A” (18.7 %) y endotropía (6.25 %). Los nervios craneales afectados fueron el III (93.75 %), VI (6.25 %) y VII (6.25 %); además, se encontró lesión a II nervio en 50 %. Conclusiones: La falla en los estadios tempranos del desarrollo del sistema nervioso central puede provocar estrabismo paralítico que secundariamente puede manifestarse como estrabismo fibrótico que afecta músculos y tejidos orbiculares, por lo que el término más apropiado sería “estrabismo fibrótico congénito como causa de dismorfogenesia de los nervios craneales”. Encontramos alta incidencia de retraso psicomotor y alteraciones neurológicas. Es importante la rehabilitación temprana y multidisciplinaria en estos pacientes.

OBJECTIVE: We undertook this study to describe central nervous system (CNS) abnormalities associated with congenital cranial dysinnervation disorders (CCDD). METHODS: This was a retrospective, observational, transversal and descriptive study including patients with congenital fibrotic strabismus. We analyzed clinical files of patients from 2001 to 2006. Neurological lesions were reported. RESULTS: Restrictive strabismus was demonstrated in all cases. Sixteen patients were included: nine males and seven females. Different neurological lesions were reported: corpus callosum anomalies, severe cortipathy, epilepsy, cavum vergae, nystagmus, occipital subarachnoid cyst, and hydrocephalus. Mental retardation was reported in 56% of patients. Different malformations were reported: genital malformations, trigonocephalus, camptodactyly, mild facial hypoplasia, low set ears, and agenesis of left ear. Blepharoptosis was present in 81% of patients. The most frequent form of strabismus was exotropia (56%), hypotropia in 37.5%, hypertropia 18.7%, "A" pattern 18.7%, and esotropia in 6.25%. Affection was cranial nerve III, 93.75%; cranial nerve VI, 6.25%; cranial nerve VII, 6.25%; and lesion to cranial nerve II in eight cases (50%). CONCLUSIONS: We have suggested that failure in early stages of embryology of the CNS can lead to the development of paralytic strabismus and generate secondary fibrotic changes, not only in muscle structures but also in other orbital tissues. That is the reason why we have used the term "congenital fibrotic strabismus" to report cases included in CCDD. We have demonstrated the strong association of mental retardation and neurological alterations. Multidisciplinary rehabilitation is relevant for these patients.