Hypoxia‐ischemia‐ (HI‐) induced oxidative stress plays a role in secondary pathocellular processes of acute spinal cord injury (SCI) due to HI from many kinds of mechanical trauma. Increasing evidence suggests that the histone deacetylase‐6 (HDAC6) plays an important role in cell homeostasis in both physiological and abnormal, stressful, pathological conditions. This paper found that inhibition of HDAC6 accelerated reactive oxygen species (ROS) generation and cell apoptosis in response to the HI. Deficiency of HDAC6 hindered the chaperone‐mediated autophagy (CMA) activity to resistance of HI‐induced oxidative stress. Furthermore, this study provided the experimental evidence for the potential role of HDAC6 in the regulation of CMA by affecting HSP90 acetylation. Therefore, HDAC6 plays an important role in the function of CMA pathway under the HI stress induced by SCI and it may be a potential therapeutic target in acute SCI model.

Background: Stroke is a disease with a high fatality rate worldwide and a major cause of long-term disability. In the rehabilitation of limb motor function after stroke, the rehabilitation of upper limb function takes a long time and the recovery progress is slow, which seriously affects the patients’ self-care ability in daily life. Repeated transcranial magnetic stimulation (rTMS) has been increasingly used to improve limb dysfunction in patients with stroke. However, a standardized reference for selecting a magnetic stimulation regimen is not available. Whether to increase the inhibition of the contralateral hemispheric motor cortex remains controversial. This study has evaluated the effects of different rTMS stimulation programs on upper limb function and corresponding brain functional network characteristics of patients with stroke and sought a new objective standard based on changes in brain network parameters to guide accurate rTMS stimulation programs.Method: Thirty-six patients with stroke were selected and divided into control group and treatment group by number table method, with 18 patients in each group, and 3 patients in the control group were turned out and lost due to changes in disease condition. The treatment group was divided into two groups. TMS1 group was given 1 Hz magnetic stimulation in the M1 region of the contralesional hemisphere +10 Hz magnetic stimulation in the M1 region of the affected hemisphere, and the TMS2 group was given 10 Hz magnetic stimulation in the M1 region of the affected hemisphere. The control group was given false stimulation. The treatment course was once a day for 5 days a week for 4 weeks. The Fugl-Meyer Assessment for upper extremity (FMA-UE) sand near-infrared brain function were collected before treatment, 2 weeks after treatment, and 4 weeks after treatment, and the brain function network was constructed. Changes in brain oxygenated hemoglobin concentration and brain network parameters were analyzed with the recovery of motor function (i.e., increased FMA score). Meanwhile, according to the average increment of brain network parameters, the rTMS stimulation group was divided into two groups with good efficacy and poor efficacy. Network parameters of the two groups before and after rTMS treatment were analyzed statistically.Results: (1) Before treatment, there was no statistical difference in Fugl-Meyer score between the control group and the magnetic stimulation group (p = 0.178).Compared with before treatment, Fugl-Meyer scores of 2 and 4 weeks after treatment were significantly increased in both groups (p <0.001), and FMA scores of 4 weeks after treatment were significantly improved compared with 2 weeks after treatment (p < 0.001). FMA scores increased faster in the magnetic stimulation group at 2 and 4 weeks compared with the control group at the same time point (p <0.001).TMS1 and TMS2 were compared at the same time point, FMA score in TMS2 group increased more significantly after 4 weeks of treatment (p = 0.010). (2) Before treatment, HbO2 content in healthy sensory motor cortex (SMC) area of magnetic stimulation group and control group was higher than that in other region of interest (ROI) area, but there was no significant difference in ROI between the two groups. After 4 weeks of treatment, the HbO2 content in the healthy SMC area was significantly decreased (p < 0.001), while the HbO2 content in the affected SMC area was significantly increased, and the change was more significant in the magnetic stimulation group (p < 0.001). (3) In-depth study found that with the recovery of motor function (FMA upper limb score increase ≥4 points) after magnetic stimulation intervention, brain network parameters were significantly improved. The mean increment of network parameters in TMS1 group and TMS2 group was significantly different (χ² = 5.844, p = 0.016). TMS2 group was more advantageous than TMS1 group in improving the mean increment of brain network parameters.Conclusion: (1) The rTMS treatment is beneficial to the recovery of upper limb motor function in stroke patients, and can significantly improve the intensity of brain network connection and reduce the island area. The island area refers to an isolated activated brain area that cannot transmit excitation to other related brain areas. (2) When the node degree of M1_Healthy region less than 0.52, it is suggested to perform promotion therapy only in the affected hemisphere. While the node degree greater than 0.52, and much larger than that in the M1_affected region. it is suggested that both inhibition in the contralesional hemisphere and high-frequency excitatory magnetic stimulation in the affected hemisphere can be performed. (3) In different brain functional network connection states, corresponding adjustment should be made to the treatment plan of rTMS to achieve optimal therapeutic effect and precise rehabilitation treatment.

Lateral ankle sprains are one of the most common musculoskeletal injuries. Up to 70% of individuals who sustain lateral ankle sprains develop chronic ankle instability (CAI). Exercise therapy is considered an effective treatment for patients with CAI. This meta-analysis investigated the efficacy of exercise therapy in CAI patients by reviewing 15 randomized controlled trials (RCTs) involving 586 participants. Databases including PubMed, EMBASE, Cochrane Library, and Web of Science were searched from inception to September 13, 2024. The Cochrane Risk of Bias Tool was used to assess study quality. Meta-analysis, sensitivity analysis, and publication bias analysis were conducted using RevMan 5.3.0 and Stata 18.0 software. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was applied to evaluate the quality of evidence. Main outcomes were assessed using the Foot and Ankle Ability Measure (FAAM) and the Star Excursion Balance Test (SEBT). The results demonstrated that exercise therapy significantly improved FAAM-S (MD = 7.98, CI: 4.11 to 11.86, p < 0.0001, I² = 30%). Long-term exercise therapy (over 4 weeks) significantly enhanced FAAM-A (MD = 10.95, CI: 6.60 to 15.29, p < 0.00001, I² = 0%) and dynamic balance ability of ankle joint (SBET-A: MD = 4.83, CI: 1.04 to 8.63, p = 0.01, I² = 62%; SEBT-PM: MD = 6.93, CI: 2.37 to 11.48, p = 0.003, I² = 69%; and SEBT-PL: MD = 8.98, CI: 2.66 to 15.29, p = 0.005, I² = 86%). After categorizing by exercise type, the results indicated that strength training was more effective in improving SEBT-PL (MD = 8.15, CI: 6.09 to 10.21, p < 0.00001, I² = 0%), joint mobilization was more effective in improving SEBT-A (MD = 7.65, CI: 4.93 to 10.37, p < 0.00001, I² = 0%), and proprioceptive training was more effective in improving SEBT-PM (MD = 10.46, CI: 5.27 to 15.65, p < 0.0001, I² = 33%). In conclusion, long-term, multifaceted exercise therapy demonstrates superior rehabilitation efficacy for patients with CAI. Personalized treatment plans, informed by SEBT assessment results, should prioritize targeted interventions such as joint mobilization, strength training, or proprioceptive training. This approach holds significant theoretical and practical value for optimizing CAI treatment strategies and enhancing patient outcomes.

Background. Glenohumeral subluxation (GHS) is common in patients with acute hemiplegia caused by stroke. GHS and upper limb function are closely related. Objective. Using musculoskeletal ultrasonography (MSUS) to objectively evaluate the efficacy of functional magnetic stimulation (FMS) in the treatment of GHS in acute hemiplegic patients after stroke. Methods. The study used prospective case control study. Stroke patients with GHS were recruited and assigned to control group and FMS group. Control group received electrode stimulation at the supraspinatus and deltoid muscles of the hemiplegic side, while FMS group was stimulated at the same locations. Before and after treatment, the distances of the acromion-greater tuberosity (AGT), acromion-lesser tuberosity (ALT), acromiohumeral distance (AHD), supraspinatus thickness (SST), and deltoid muscle thickness (DMT) in patients’ bilateral shoulder joint were measured by MSUS, respectively. Meanwhile, Fugl-Meyer Assessment (FMA) was used to evaluate the improvement of upper limb function. Results. 30 patients were recruited. After FMS treatment, there was a significant decrease in the difference value between ipsilateral side and contralateral side of AGT [t=8.595, P<0.01], ALT [t=11.435, P<0.01], AHD [t=8.375, P<0.01], SST [t=15.394, P<0.01], and DMT [t=24.935, P<0.01], and FMA score increased [t=-13.315, P<0.01]. Compared with control group, FMS group decreased more significantly in the difference value between ipsilateral side and contralateral side of AGT [t=2.161, P<0.05], ALT [t=3.332, P<0.01], AHD [t=8.768, P<0.01], SST [t=6.244, P<0.01], and the DMT [t=3.238, P<0.01], and FMA score increased more significantly in FMS group [t=7.194, P<0.01]. Conclusion. The study preliminarily shows that the MSUS can objectively and dynamically evaluate the treatment effect of GHS in hemiplegic patients. Meanwhile, compared with control group, the FMS is more effective and has fewer side effects, and the long-term effect of FMS is worth further study. This trial is registered with ChiCTR1800015352.

Spinal cord injury (SCI) is a severe condition with an extremely high disability rate. It is mainly manifested as the loss of motor, sensory and autonomic nerve functions below the injury site. High-frequency transcranial magnetic stimulation, a recently developed neuromodulation method, can increase motor function in mice with spinal cord injury. This study aimed to explore the possible mechanism by which transcranial magnetic stimulation (TMS) restores motor function after SCI. A complete T8 transection model of the spinal cord was established in mice, and the mice were treated daily with 15 Hz high-frequency transcranial magnetic stimulation. The BMS was used to evaluate the motor function of the mice after SCI. Western blotting and immunofluorescence were used to detect the expression of Connexin43 (CX43) and autophagy-related proteins in vivo and in vitro, and correlation analysis was performed to study the relationships among autophagy, CX43 and motor function recovery after SCI in mice. Western blotting was used to observe the effect of magnetic stimulation on the expression of mTOR pathway members. In the control group, the expression of CX43 was significantly decreased, and the expression of microtubule-associated protein 1 A/1b light chain 3 (LC3II) and P62 was significantly increased after 4 weeks of spinal cord transection. After high-frequency magnetic stimulation, the level of CX43 decreased, and the levels of LC3II and P62 increased in primary astrocytes. The BMS of the magnetic stimulation group was greater than that of the control group. High-frequency magnetic stimulation can inhibit the expression of CX43, which negatively regulates autophagic flux. HF-rTMS increased the expression levels of mTOR, p-mTOR and p-S6. Our experiments showed that rTMS can restore hindlimb motor function in mice after spinal cord injury via regulation of the Cx43-autophagy loop and activation of the mTOR signalling pathway.