To better analyze the problem of abnormal neuromuscular coupling related to motor dysfunction for stroke patients, the functional coupling of the multichannel electromyography (EMG) were studied and the difference between stroke patients and healthy subjects were further analyzed to explore the pathological mechanism of motor dysfunction after stroke. Firstly, the cross-frequency coherence (CFC) analysis and non-negative matrix factorization (NMF) were combined to construct a CFC-NMF model to study the linear coupling relationship in bands and the nonlinear coupling characteristics in different frequency ratios during elbow flexion and extension movement. Furthermore, the significant coherent area and sum of cross-frequency coherence were respectively calculated to quantitatively describe the intermuscular linear and nonlinear coupling characteristics. The results showed that the linear coupling relationship between multichannel muscles was different in frequency bands and the overall coupling was stronger in low frequency band. The linear coupling strength of the stroke patients was lower than that of the healthy subjects in different frequency bands especially in beta and gamma bands. For the nonlinear coupling, the intermuscular coupling strength of stroke patients in different frequency ratios was significantly lower than that of the healthy subjects, and the coupling strength in the frequency ratio 1∶2 was higher than that in the frequency ratio 1∶3. This method can provide a theoretical basis for exploring the intermuscular coupling mechanism of patients with motor dysfunction.
Case-Control Studies ; Electromyography ; Humans ; Muscle, Skeletal ; physiopathology ; Stroke ; physiopathology ; Stroke Rehabilitation

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons with no effective cure. Electrophysiological studies have found decremental responses during low-frequency repetitive nerve stimulation (RNS) except for diffused neurogenic activities. However, the difference between ALS and generalized myasthenia gravis (GMG) in terms of waveform features is unclear. In the current study, we explored the variation trend of the amplitudes curve between ALS and GMG with low-frequency, positive RNS, and the possible mechanism is discussed preliminarily. METHODS: A total of 85 ALS patients and 41 GMG patients were recruited. All patients were from Peking Union Medical College Hospital (PUMCH) between July 1, 2012 and February 28, 2015. RNS study included ulnar nerve, accessory nerve and facial nerve at 3 Hz and 5 Hz stimulation. The percentage reduction in the amplitude of the fourth or fifth wave from the first wave was calculated and compared with the normal values of our hospital. A 15% decrease in amplitude is defined as a decrease in amplitude. RESULTS: The decremental response at low-frequency RNS showed the abnormal rate of RNS decline was 54.1% (46/85) in the ALS group, and the results of different nerves were 54.1% (46/85) of the accessory nerve, 8.2% (7/85) of the ulnar nerve and 0% (0/85) of the facial nerve stimulation, respectively. In the GMG group, the abnormal rate of RNS decline was 100% (41/41) at low-frequency RNS of accessory nerves. However, there was a significant difference between the 2 groups in the amplitude after the sixth wave. CONCLUSIONS Both groups of patients are able to show a decreasing amplitude of low-frequency stimulation RNS, but the recovery trend after the sixth wave has significant variation. It implies the different pathogenesis of NMJ dysfunction of these 2 diseases.
Action Potentials ; physiology ; Adult ; Aged ; Amyotrophic Lateral Sclerosis ; physiopathology ; therapy ; Electric Stimulation Therapy ; Electromyography ; Female ; Humans ; Male ; Median Nerve ; physiology ; Middle Aged ; Motor Neurons ; physiology ; Muscle, Skeletal ; physiology ; Myasthenia Gravis ; physiopathology ; therapy ; Retrospective Studies ; Ulnar Nerve ; physiology

OBJECTIVE: To investigate the mechanism of congenital paramyotonia caused by human skeletal muscle voltage-gated sodium channel hNav1.4 mutant I1363T. METHODS: The conservation of the mutant site were detecled by using amino acid sequence alignment; the C-terminal mCherry fusion hNav1.4 was constructed, and the expression and distribution of wild type and hNav1.4 mutant I1363T were determined by confocal microscopy; the steady-state activation, fast inactivation and window current of wild type and hNav1.4 mutant I1363T were examined by whole-cell patch clamp. RESULTS: Alignment of the amino acid sequences revealed that Ile1363 is highly conserved in human sodium channels. There was no significant difference in expression level and distribution between wild type and I1363T. Although no significant differences were observed between I1363T mutant and wild type in the activation upon channel gating, the of voltage-dependence of fast inactivation of I1363T mutant[(-59.01±0.26) mV] shifted 9 mV towards depolarization as compared with wild type[(-68.03±0.34) mV], and the slope factor of voltage-dependence curve increased to (5.24±0.23) mV, compared with (4.55±0.21) mV of the wild type. Moreover, I1363T showed the larger window current than that of the wild type. CONCLUSIONS I1363T causes the defect in fast inactivation of hNav1.4, which may increase the excitability of muscle cells and be responsible for myotonia. The increased window current of I1363T may result in an increase of inward Na+ current, could subsequently inactivate the channels and lead to loss of excitability and paralysis.
Gene Expression Profiling ; Humans ; Ion Channel Gating ; genetics ; Muscle, Skeletal ; physiopathology ; Mutation ; NAV1.4 Voltage-Gated Sodium Channel ; genetics ; Sequence Analysis, Protein

Objective To investigate diabetes-mediated changes in the neuromuscular pharmacodynamics of rocuronium in rats. Methods Diabetes mellitus was induced by a single injection of streptozotocin in rats.A total of 24 male SD rats were assigned to four groups using random number table:the normal control group,diabetic 2-week group,diabetic 4-week group,and diabetic 8-week group(6 rats per group).The sciatic nerve was stimulated in a rain-of-four(TOF)pattern,and the twitch tension changes in the tibialis anterior muscle were demonstrated by mechanomyography after intravenous injection of rocuronium in vivo.The time course characteristics of rocuronium,including onset time,and the recovery time from rocuronium injection to TOF ratio 75%(RT75%)and 90%(RT90%),were recorded,and half maximal inhibitory concentration(IC)values of rocuronium were determined using a four-parameter dose response curve. Results Compared with the normal controls,the diabetic rats had significantly prolonged onset time of rocuronium,while the RT75% and RT90% were decreased at all rocuronium doses(P<0.001).The time course changes became increasingly significant as the duration of diabetes lengthened(P<0.001).The IC and 95% confidence interval values for rocuronium in the normal control group,diabetic 2-week group,diabetic 4-week group,and diabetic 8-week group were 0.37(0.35-0.38)mg/kg,0.44(0.43-0.46)mg/kg,0.59(0.57-0.61)mg/kg,and 0.64(0.61-0.66)mg/kg,respectively.IC values were significantly higher in the diabetic groups vs.normal control(P<0.001)and gradually increased as the duration of diabetes lengthened(P<0.001).Conclusion Diabetes is associated with the rat skeletal muscle hyposensitivity to rocuronium,which is featured by prolonged onset time of rocuronium,decreased RT 75% and RT 90%,and right shift of the cumulative dose-response curve of rocuronium.
Animals ; Diabetes Mellitus, Experimental ; physiopathology ; Male ; Muscle, Skeletal ; drug effects ; Neuromuscular Nondepolarizing Agents ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rocuronium ; pharmacology

OBJECTIVE: To investigate the therapeutic effects of massage on denervated skeletal muscle atrophy in rats and its mechanism. METHODS: Forty-eight male SD rats were randomly divided into model group (n=24) and massage group (n=24). Gastrocnemius muscle atrophy model was established by transecting the right tibial nerve of rat. On the second day after operation, the gastrocnemius muscle of the rats in the massage group was given manual intervention and the model group was not intervened. Six rats were sacrificed at the four time points of 0 d, 7 d, 14 d and 21 d. The gastrocnemius of the rats were obtained and measured the wet mass ratio after weighing. Cross-sectional area and diameter of the muscle fiber were measured after HE staining. The relative expressions of miR-23a, Akt, MuRF1 and MAFbx mRNA were tested with qPCR. RESULTS: Compared with 0 d, the wet weight ratio, cross-sectional area and diameter of gastrocnemius muscle showed a progressive decline in the model group and massage group. The wet weight ratio, cross-sectional area and diameter of gastrocnemius muscle in the massage group were higher than those in the model group on 7 d, 14 d and 21 d (P＜0.05, P＜0.01). Compared with 0 d, the expressions of MuRF1, MAFbx and Akt mRNA were increased first and then were decreased in the model group and massage group. The expression of MuRF1 mRNA in massage group was lower than that in model group on 7 d and 21 d (P＜0.05, P＜0.01). The expression of MAFbx mRNA in massage group was lower than that in model group on 7 d, 14 d and 21 d (P＜0.01, P＜0.05, P＜0.01). The expression of Akt mRNA in massage group was higher than that in model group on 7 d, 14 d and 21 d (P＜0.05, P＜0.01). Compared with 0 d, the expression of miR-23a mRNA was increased in the model group and massage group on 21 d, and the expression of miR-23a mRNA in massage group was higher than that in model group (P＜ 0.05). CONCLUSION Massage can delay the atrophy of denervated skeletal muscle. The mechanism may be related to up-regulation of the expression of miR-23a and Akt mRNA, down-regulation of the expressions of MuRF1 and MAFbx mRNA, inhibition of protein degradation rate, and reduction of skeletal muscle protein degradation.
Animals ; Male ; Massage ; MicroRNAs ; metabolism ; Muscle Fibers, Skeletal ; Muscle Proteins ; metabolism ; Muscle, Skeletal ; physiopathology ; Muscular Atrophy ; therapy ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Sprague-Dawley ; SKP Cullin F-Box Protein Ligases ; metabolism ; Tripartite Motif Proteins ; metabolism ; Ubiquitin-Protein Ligases ; metabolism

OBJECTIVE: To explore the clinical features of a Chinese pedigree affected with skeletal muscle sodium channelopathies due to variation of SCN4A gene. METHODS: Potential variation of the 24 exons of the SCN4A gene was screened using PCR and Sanger sequencing. RESULTS: Four family members were affected with the disease in an autosomal dominant inheritance pattern. Three patients had normekalemic periodic paralysis, while 1 showed paramyotonia congenita. Genetic analysis detected a missense variation c.2078T>C (p.Ile693Thr) in exon 13 of the SCN4A gene in the proband and other 3 affected relatives. CONCLUSION Normokalemic periodic paralysis and paramyotonia congenita can occur in different family members with skeletal muscle sodium channelopathies due to c.2078T>C(p.Ile693Thr) variation of SCN4A gene.
Channelopathies ; genetics ; Humans ; Muscle, Skeletal ; physiopathology ; Mutation ; NAV1.4 Voltage-Gated Sodium Channel ; genetics ; Pedigree

Pelvic floor muscle exercise (PFME) is the most common conservative management for urinary incontinence (UI) after radical prostatectomy (RP). However, whether the PFME guided by a therapist (G-PFME) can contribute to the recovery of urinary continence for patients after RP is still controversial. We performed this meta-analysis to investigate the effectiveness of G-PFME on UI after RP and to explore whether the additional preoperative G-PFME is superior to postoperative G-PFME alone. Literature search was conducted on Cochrane Library, Embase, Web of Science, and PubMed, to obtain all relevant randomized controlled trials published before March 1, 2018. Outcome data were pooled and analyzed with Review Manager 5.3 to compare the continence rates of G-PFME with control and to compare additional preoperative G-PFME with postoperative G-PFME. Twenty-two articles with 2647 patients were included. The continence rates of G-PFME were all superior to control at different follow-up time points, with the odds ratio (OR) (95% confidence interval [CI]) of 2.79 (1.53-5.07), 2.80 (1.87-4.19), 2.93 (1.19-7.22), 4.11 (2.24-7.55), and 2.41 (1.33-4.36) at 1 month, 3 months, 4 months, 6 months, and 12 months after surgery, respectively. However, there was no difference between additional preoperative G-PFME and postoperative G-PFME, with the OR (95% CI) of 1.70 (0.56-5.11) and 1.35 (0.41-4.40) at 1 month and 3 months after RP, respectively. G-PFME could improve the recovery of urinary continence at both early and long-term stages. Starting the PFME preoperatively might not produce extra benefits for patients at early stage, compared with postoperative PFME.
Humans ; Male ; Muscle, Skeletal/physiopathology* ; Pelvic Floor/physiopathology* ; Physical Therapy Modalities ; Prostatectomy/adverse effects* ; Prostatic Neoplasms/surgery* ; Treatment Outcome ; Urinary Incontinence/therapy*

OBJECTIVESTo explore the possible biological mechanism of skeletal muscle contusion repair through researching the changes in expression of autophagy-related genes and proteins in SD rats with acute skeletal muscle contusion.

METHODSSix rats were randomly selected as the control group from 30 male SD rats, acute skeletal muscle contusion model were established in the remaining 24 rats with self-made hitter, then the model rats were randomly divided into 4 groups (3 d, 5 d, 7 d, 14 d groups, =6). On the 3, 5, 7 and 14 day after injury, injured gastrocnemius of each group was harvested. The morphological and the ultra-microstructure changes of gastrocnemius after injury were observed by HE staining and transmission electron microscope (TEM) respectively. The relative protein levels of (LC3-Ⅱ) and P62 of each group were observed by Western blot. The relative mRNA levels of atg7, atg10, atg12, atg16L1 of each group were observed by RTPCR.

RESULTSThe results of HE staining showed that compared with the control group, the inflammation reached its peak on the 5 day after injury, new muscle fibers were clearly observed in 7 d group. The results of TEM showed that, compared with the control group, oncotic mitochondria could be clearly seen in the 3 d, 5 d, 7 d groups. Also, the Z line changed from disappearing to drift thickening, sarcoplasmic reticulum dilatation gradually improved, there was no evident difference between the 14 d group and the control group, suggesting that the damage has preliminarily healed. The results of Western blot showed that the expressions of LC3-Ⅱand P62 were increased at first and then decreased. The expression of LC3-Ⅱwas markedly up-regulated in the 3 d, 5 d, 7 d groups compared with the control group and the 14 d group (<0.01). Similarly, compared with the control group, the expression of P62 reached its peak on the 3 day after injury (<0. 01), and returned to normal level on the 14 day. The results of RT-PCR showed that the expression of atg10 mRNA in the natural recovery group of 3 d, 5 d, 7 d, 14 d was firstly decreased and then increased, the atg10 mRNA was markedly down-regulated in the 3 d, 5 d, 7 d groups compared with the control group and the 14 d group (<0. 01). The expression of atg7, atg12, atg16L1 mRNA was generally increased at first and then decreased, it was markedly up-regulated in the 3 d, 5 d, 7 d groups compared with the control group and the 14 d group (<0.01, <0.05, <0.01).

CONCLUSIONSThe above results indicate that the autophagy is involved in repair of skeletal muscle injury by its autophagyrelated factors,regularly changes after contusion, and the rate of damage repair may be related to the level of autophagy.

Animals ; Autophagy ; Contusions ; physiopathology ; Male ; Muscle, Skeletal ; injuries ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley

The increase in the proportion of elderly people in the population is one of the most remarkable sociodemographic phenomena of the twenty-first century. The number of patients with diabetes is also increasing worldwide with this demographic change. Given these facts, consideration of the problems the general elderly population is facing in the management of diabetes is essential. In this review article, we focus on sarcopenia, which is the decrease in lower extremity muscle mass and muscle strength accompanying aging, describe the relationship between sarcopenia and diabetes, and highlight the specific factors through which diabetes contributes to loss of muscle strength. The quantitative methods for evaluating lower extremity muscle strength will also be described. These methods hold the key to assessing the effectiveness of exercise therapy and optimizing the assessment of the degree of autonomy in the activities of daily living. Exercise is one of the basic treatments for type 2 diabetes and may also prevent and improve sarcopenia. This review discusses the aspects common to the two health conditions and elucidates the effectiveness and necessity of exercise as a preventive measure against diabetes among the elderly.
Aged ; Aged, 80 and over ; Diabetes Mellitus, Type 2 ; physiopathology ; prevention & control ; Exercise Therapy ; Female ; Humans ; Leg ; physiopathology ; Male ; Muscle Strength ; physiology ; Muscle, Skeletal ; physiology ; Sarcopenia ; physiopathology ; prevention & control

Adult ; Arterial Occlusive Diseases ; diagnosis ; Constriction, Pathologic ; diagnosis ; Humans ; Male ; Martial Arts ; Muscle, Skeletal ; pathology ; Pain ; diagnosis ; Peripheral Vascular Diseases ; diagnosis ; Popliteal Artery ; physiopathology ; Singapore