NAD+ affects differentially expressed genes-MBOAT2-SLC25A21-SOX6 in experimental autoimmune encephalomyelitis model.

BACKGROUND: Nicotinamide adenine dinucleotide (NAD+) plays a key role in neuroinflammation and neurodegeneration and provides anti-inflammatory and neuroprotective effects in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). AIM: In this study, we aimed to investigate whether NAD+ affects differentially expressed genes (DEGs) in splenocytes of EAE mice to reveal candidate genes for the pathogenesis of MS. METHODS: The EAE model was used to perform an intervention on NAD+ to investigate its potential as a protective agent in inflammation and demyelination. Transcriptome analysis of nerve tissue was carried out to gain better insights into NAD+ function. Effects of NAD+ on DEGs in the splenocytes of EAE mice were investigated to determine its anti-inflammatory effect. RESULTS: NAD+ in EAE mice showed the clinical score was significantly improved (EAE 3.190 ± 0.473 vs. NAD+ 2.049 ± 0.715). DEGs (MBOAT2, SLC25A21, and SOX6) between the EAE and the EAE + NAD+ groups showed that SOX6 was significantly improved after NAD+ treatment compared with the EAE group, and other indicators were improved but did not reach statistical significance. NAD+ exhibited clinical scores in EAE mice, and key inflammation was ameliorated in EAE mice spleen after NAD+ intervention, while transcriptome analysis between EAE and EAE + NAD+ groups showed several DEGs in the underlying mechanism. CONCLUSION: NAD+ on DEGs attenuates disease severity in EAE. Transcriptome analysis on nerve tissue reveals several protein targets in the underlying mechanisms. However, NAD+ does not significantly improve DEGs in the splenocytes of the EAE model.

MBOAT2, SLC25A21, and SOX6 show significant fold change in EAE mice, while SOX6 shows significantly lower expression in the EAE group and the EAE + NAD⁺ group compared with the Ctrl.NAD⁺ in the EAE model provides its protective role in inflammation and demyelination.NAD⁺ exhibits clinical scores in EAE mice.NAD⁺ does not significantly improve DEGs in splenocytes of the EAE.

Effectiveness of Mirror Therapy for Phantom Limb Pain: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness of mirror therapy (MT) for phantom limb pain (PLP). DATA SOURCES: PubMed, EMBASE, Ovid MEDLINE, Scopus, Cochrane Library, Physiotherapy Evidence Database, CNKI, and WanFang Data were used to search for studies published up to March 31, 2021. STUDY SELECTION: Randomized controlled trials (RCTs) comparing the pain intensity of MT for PLP were performed. A total of 2094 articles were found. Among them, 10 were eligible for the final analysis. DATA EXTRACTION: The quality of the RCTs was assessed using the Physiotherapy Evidence Database (PEDro) scale by 2 independent reviewers. Outcome data were pooled according to follow-up intervals (1, 3, 6, and 12mo). Duration times were used as a basis for distinguishing subgroups. The primary evaluation was by visual analog scale. The PEDro scale was used to assess the methodological quality of studies. DATA SYNTHESIS: Meta-analysis revealed a statistically significant decrease in pain in the MT group vs the control group within 1 month (I2=0%; standardized mean difference [SMD]=-0.46, 95% confidence interval [CI], -0.79 to -0.13; P = .007). The patients with pain for longer than 1 year benefited more from MT (I2=0%; SMD=-0.46; 95% CI, -0.85 to -0.07; P = .02). CONCLUSIONS: MT has beneficial effects for patients with PLP in the short-term, as evidenced by their improved pain scores. There was no evidence that MT had a long-term effect, but that may be a product of limited data. For patients with long-term PLP, MT may be an effective treatment.

Comparison of three treatment methods for simple bone cyst in children.

BACKGROUND: The unicameral bone cyst (UBC) is a kind of benign tumor whose clinical treatments and efficacy are controversial. The purpose of this study was to evaluate the efficacy of the elastic stable intramedullary nail (ESIN), the injection of autologous bone marrow (ABM), and the combination of ESIN and ABM in the treatment of bone cyst in children. METHODS: Eighty-three cases with simple bone cyst were analyzed retrospectively. Twenty-eight cases were treated with ABM. Twenty-eight cases were treated with ESIN. Twenty-seven cases were treated with ABM and ESIN. All cases were diagnosed through X-ray, CT, or MRI scans. For the suspicious ones, the pathological biopsy was performed for an accurate diagnosis. X-ray examinations were carried out for the postoperative follow-up. Capanna criteria for bone cyst was used for postoperative evaluation of three methods. RESULTS: All cases accomplished the follow-up. The effective rate of the ABM + ESIN group was significantly higher than that of the ABM group (P < 0.05), and the cure rates of the ESIN group and the ABM + ESIN group were higher than that of the ABM group (P < 0.05, respectively). The cure time in the ESIN group was lower than that of the other two groups (P < 0.05, respectively). The times for admission were 2.0 ± 0.0 in the ESIN group, 5.7 ± 1.9 in the ABM group, and 4.7 ± 2.4 in the ABM + ESIN group (P < 0.05 when compared with each other). CONCLUSIONS: The method of ABM combined with ESIN for children's bone cyst has the highest effective rate and curative rate. For the individual method, ESIN has a higher effective rate and curative rate than that of ABM. Meanwhile, it has the fewest time of hospitalization.

A Meta-Analysis and Systematic Review of the Incidences of Complications Following Facial Thread-Lifting.

BACKGROUND: Facial thread-lifting (FTL) has gained more popularity, but the incidences of complications following FTL remain controversial. We aimed to perform a meta-analysis and systematic review to estimate the incidences of complications and to compare the short- and long-term satisfaction rates following FTL. METHODS: We searched PubMed, Web of Science, Embase and Cochrane library for eligible studies. The primary outcome was the incidences of complications following FTL. The secondary outcome was the satisfaction rate immediately and 6-month after FTL. The pooled incidences of complications and 95% confidence intervals were estimated using random-effects models. RESULTS: A total of 26 studies were included in this meta-analysis. Swelling was the most commonly reported complication with a pooled incidence of 35%, followed by skin dimpling (10%), paresthesia (6%), thread visibility/palpability (4%), infection (2%), and thread extrusion (2%). Absorbable threads were associated with a significantly lower risk of paresthesia (3.1% vs. 11.7%) and thread extrusion (1.6% vs. 7.6%) than non-absorbable threads. Patients older than 50 years had a significantly higher risk of dimpling (16% vs. 5.6%) and infection (5.9% vs. 0.7%) than their younger counterparts. In addition, the pooled long-term satisfaction rate was significantly decreased compared to it immediately after FTL (88% vs. 98%). CONCLUSION: Non-absorbable threads and older age of patients are associated with higher risks of complications. Therefore, we recommend a judicious use of non-absorbable threads and FLT in older patients. Furthermore, it should be discussed with patients preoperatively that the rejuvenation effect of FTL may not maintain in the long-term. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Early-phase rotator training impairs tissue repair and functional recovery after spinal cord injury.

Spinal cord injury (SCI) is a devastating disorder that often results in severe sensorimotor function impairment with limited recovery of function. In recent years, rehabilitation training for spinal cord injury has gradually emerged, and some of them play an important role in the repair of spinal cord injury However, the optimal training regimen for SCI remains to be determined. In this study, we explore the effects of rotarod training (began at 7 days post-injury) on the recovery of motor function after SCI, as well as its possible repair mechanism from the aspects of function and histopathological changes, the behaviors of specific trophic factors and cytokines, and the expression profile of specific genes. Multiple functional assessments showed that rotarod training initiated at 7 days post-injury is unsuitable for promoting neuro-electrophysiological improvement and trunk stability, but impaired functional coordination and motor recovery. In addition, rotarod training has negative effects on spinal cord repair after SCI, which is manifested as an increase of lesion area, a decrease in neuronal viability, a deterioration in immuno-microenvironment and remyelination, a significant reduction in the expression of trophic factors and an increase in the expression of pro-inflammatory factors. RNA sequencing suggested that the genes associated with angiogenesis and synaptogenesis were significantly downregulated and the PI3K-AKT pathway was inhibited, which was detrimental to spinal cord repair and impeded nerve regeneration. These results indicate that immediate rotarod training after SCI is currently unsuitable for rehabilitation in mice.

Emerging Roles of Microglia Depletion in the Treatment of Spinal Cord Injury.

Microglia, as the resident immune cells and first responder to neurological insults, play an extremely important role in the pathophysiological process of spinal cord injury. On the one hand, microglia respond rapidly and gather around the lesion in the early stage of injury to exert a protective role, but with the continuous stimulation of the injury, the excessive activated microglia secrete a large number of harmful substances, aggravate the injury of spinal cord tissue, and affect functional recovery. The effects of microglia depletion on the repair of spinal cord injury remain unclear, and there is no uniformly accepted paradigm for the removal methods and timing of microglia depletion, but different microglia depletion strategies greatly affect the outcomes after spinal cord injury. Therefore, this review summarizes the physiological and pathological roles of microglia, especially the effects of microglia depletion on spinal cord injury-sustained microglial depletion would aggravate injury and impair functional recovery, while the short-term depletion of microglial population in diseased conditions seems to improve tissue repair and promote functional improvement after spinal cord injury. Furthermore, we discuss the advantages and disadvantages of major strategies and timing of microglia depletion to provide potential strategy for the treatment of spinal cord injury.

Synaptic remodeling in mouse motor cortex after spinal cord injury.

Spinal cord injury dramatically blocks information exchange between the central nervous system and the peripheral nervous system. The resulting fate of synapses in the motor cortex has not been well studied. To explore synaptic reorganization in the motor cortex after spinal cord injury, we established mouse models of T12 spinal cord hemi-section and then monitored the postsynaptic dendritic spines and presynaptic axonal boutons of pyramidal neurons in the hindlimb area of the motor cortex in vivo. Our results showed that spinal cord hemi-section led to the remodeling of dendritic spines bilaterally in the motor cortex and the main remodeling regions changed over time. It made previously stable spines unstable and eliminated spines more unlikely to be re-emerged. There was a significant increase in new spines in the contralateral motor cortex. However, the low survival rate of the new spines demonstrated that new spines were still fragile. Observation of presynaptic axonal boutons found no significant change. These results suggest the existence of synapse remodeling in motor cortex after spinal cord hemi-section and that spinal cord hemi-section affected postsynaptic dendritic spines rather than presynaptic axonal boutons. This study was approved by the Ethics Committee of Chinese PLA General Hospital, China (approval No. 201504168S) on April 16, 2015.

Comparative study of the reorganization in bilateral motor and sensory cortices after spinal cord hemisection in mice.

OBJECTIVE: The effects of spinal cord injury (SCI) on sensorimotor cortex plasticity have not been well studied. Therefore, to explore the reorganization after SCI, we dynamically monitored postsynaptic dendritic spines of pyramidal neurons in vivo. METHODS: Thy1-YFP transgenic mice were randomly divided into two groups: the control and SCI group. We then opened the spinal vertebral plates of all mice and sectioned one-half of the spinal cord in SCI group. The relevant areas were imaged bilaterally at 0, 3, 14 and 28 days post-SCI. The rates of elimination, formation and stable spines were evaluated. RESULTS: At the early stage, the rate of stable and elimination spines experienced a similar change trend. But the rate of formation spines in the contralateral sensory cortex was significantly increased after SCI compared with those in the control group. At the late stage, spines of three types remodeled very differently between the sensory and motor cortex. Compared with those in the control group, spines in the bilateral sensory cortex demonstrated obvious differences in the rate of stable and elimination spines but not formation spines, while spines in the motor cortex, especially in the contralateral cortex increased significantly in the rate of formation after SCI. As for survival rate, differences mainly appeared in time frame instead of cortex type or region. CONCLUSIONS: The dendritic spines in hindlimb representation area of the sensorimotor cortex experienced bilaterally remodeling after SCI. And those spines in the sensory and motor cortex experienced great but different change trends after SCI.

3D-printed models improve surgical planning for correction of severe postburn ankle contracture with an external fixator.

Gradual distraction with an external fixator is a widely used treatment for severe postburn ankle contracture (SPAC). However, application of external fixators is complex, and conventional two-dimensional (2D) imaging-based surgical planning is not particularly helpful due to a lack of spatial geometry. The purpose of this study was to evaluate the surgical planning process for this procedure with patient-specific three-dimension-printed models (3DPMs). In this study, patients coming from two centers were divided into two cohorts (3DPM group vs. control group) depending on whether a 3DPM was used for preoperative surgical planning. Operation duration, improvement in metatarsal-tibial angle (MTA), range of motion (ROM), the American Orthopedic Foot and Ankle Society (AOFAS) scores, complications, and patient-reported satisfaction were compared between two groups. The 3DPM group had significantly shorter operation duration than the control group ((2.0±0.3) h vs. (3.2±0.3) h, P<0.01). MTA, ROM, and AOFAS scores between the two groups showed no significant differences pre-operation, after the removal of the external fixator, or at follow-up. Plantigrade feet were achieved and gait was substantially improved in all patients at the final follow-up. Pin-tract infections occurred in two patients (one in each group) during distraction and were treated with wound care and oral antibiotics. Patients in the 3DPM group reported higher satisfaction than those in the control group, owing to better patient-surgeon communication. Surgical planning using patient-specific 3DPMs significantly reduced operation duration and increased patient satisfaction, while providing similar improvements in ankle movement and function compared to traditional surgical planning for the correction of SPAC with external fixators.

[Treatment of long bone cyst in children by autologous bone marrow blood injection and elastic intramedullary needle].

OBJECTIVE: To observe the clinical effect of autologous bone marrow blood injection combined with elastic intramedullary needle implantation in the treatment of long bone cyst in children. METHODS: From January 2010 to December 2015, 29 children with long bone cyst were treated with autologous bone marrow blood injection combined with elastic intramedullary nail implantation, including 22 males and 7 females, aged 2 to 12 years old with an average age of 7.7 years old, and the course of disease was 12 to 84 months. Among them, 17 cases were proximal humerus, 9 cases were proximal femur, 2 cases were distal femur and 1 case was proximal ulna. All children with bone cyst underwent preoperative X-ray examination and CT or MRI examination if necessary. After definite diagnosis, bone marrow blood injection combined with elastic intramedullary needle support and drainage were used as treatment methods. After operation, multiple X-ray examination and follow-up were carried out. The curative effect was evaluated with Capanna bone cyst treatment evaluation criteria. RESULTS: Twenty-seven of 29 children were followed up for 12 to 60 months with an average of 31.8 months. According to the evaluation criteria of Capanna bone cyst, 26 cases were cured and 1 case was partially healed with residual lesions. CONCLUSIONS: Autologous bone marrow blood injection combined with elastic intramedullary needle has the characteristics of definite curative effect, high cure rate, fewer complications and objectively controllable treatment process for simple long bone cyst in children.

[Comparison of the efficacy between elastic intramedullary injection and autologous bone marrow blood injection in the treatment of bone cyst in children].

OBJECTIVE: To evaluate the efficacy of autogenous bone marrow injection and elastic intramedullary injection in the treatment of bone cyst in children. METHODS: From January 2012 to December 2016, 56 children with simple bone cyst were divided into two groups: autogenous bone marrow blood injection group and elastic intramedullary needle group. There were 28 cases in the autogenous bone marrow blood injection group, 16 boys and 12 girls, aged (7.7±1.9) years old, 10 cases of proximal humerus, 8 cases of proximal femur, 6 cases of proximal tibia and 4 cases of femoral shaft. In the elastic intramedullary needle group, there were 28 cases, 18 boys and 10 girls, aged(7.5±2.2) years old, 11 cases of proximal humerus, 7 cases of proximal femur, 5 cases of proximal tibia, 4 cases of femoral shaft and 1 case of distal femur. The treatment effect was evaluated by Capanna standard. RESULTS: All the patients were followed up, including 17 to 35(25.6±4.2) months in the elastic intramedullary needle group and 19 to 35(27.4±4.8) months in the autogenous marrow blood injection group. According to Capanna's evaluation standard of bone cyst, 27 patients in the elastic intramedullary needle group were treated effectively(25 patients cured, 2 patients healed but some remained lesions), 1 patients recurred, 0 patient had no response to treatment; 18 patients in the autogenous bone marrow blood injection group were treated effectively(13 patients cured, 5 patients healed but some remained lesions), 8 patients of cyst recurred, 2 patients had no response to treatment; the difference between the two groups was statistically significant(P<0.01). The overall cure time was calculated by the follow-up of 25 cases in the elastic intramedullary injection group and 13 cases in the autogenous marrow blood injection group. The cure time was(20.2±3.5) months in the elastic intramedullary injection group and(27.7±4.9) months in the autogenous marrow blood injection group. The difference was statistically significant(P<0.05). CONCLUSIONS: For the treatment of bone cyst in children, the therapeutic effect of elastic intramedullary needle is better than that of autogenous bone marrow blood injection, and the cure time is shorter.

Pinning Impulsive Synchronization of Reaction-Diffusion Neural Networks With Time-Varying Delays.

This paper investigates the exponential synchronization of reaction-diffusion neural networks with time-varying delays subject to Dirichlet boundary conditions. A novel type of pinning impulsive controllers is proposed to synchronize the reaction-diffusion neural networks with time-varying delays. By applying the Lyapunov functional method, sufficient verifiable conditions are constructed for the exponential synchronization of delayed reaction-diffusion neural networks with large and small delay sizes. It is shown that synchronization can be realized by pinning impulsive control of a small portion of neurons of the network; the technique used in this paper is also applicable to reaction-diffusion networks with Neumann boundary conditions. Numerical examples are presented to demonstrate the effectiveness of the theoretical results.

Remodeling the Dendritic Spines in the Hindlimb Representation of the Sensory Cortex after Spinal Cord Hemisection in Mice.

Spinal cord injury (SCI) can induce remodeling of multiple levels of the cerebral cortex system especially in the sensory cortex. The aim of this study was to assess, in vivo and bilaterally, the remodeling of dendritic spines in the hindlimb representation of the sensory cortex after spinal cord hemisection. Thy1-YFP transgenic mice were randomly divided into the control group and the SCI group, and the spinal vertebral plates (T11-T12) of all mice were excised. Next, the left hemisphere of the spinal cord (T12) was hemisected in the SCI group. The hindlimb representations of the sensory cortex in both groups were imaged bilaterally on the day before (0d), and three days (3d), two weeks (2w), and one month (1m) after the SCI. The rates of stable, newly formed, and eliminated spines were calculated by comparing images of individual dendritic spine in the same areas at different time points. In comparison to the control group, the rate of newly formed spines in the contralateral sensory cortex of the SCI group increased at three days and two weeks after injury. The rates of eliminated spines in the bilateral sensory cortices increased and the rate of stable spines in the bilateral cortices declined at two weeks and one month. From three days to two weeks, the stable rates of bilaterally stable spines in the SCI group decreased. In comparison to the control group and contralateral cortex in the SCI group, the re-emerging rate of eliminated spines in ipsilateral cortex of the SCI group decreased significantly. The stable rates of newly formed spines in bilateral cortices of the SCI group decreased from two weeks to one month. We found that the remodeling in the hindlimb representation of the sensory cortex after spinal cord hemisection occurred bilaterally. This remodeling included eliminating spines and forming new spines, as well as changing the reorganized regions of the brain cortex after the SCI over time. Soon after the SCI, the cortex was remodeled by increasing spine formation in the contralateral cortex. Then it was remodeled prominently by eliminating spines of bilateral cortices. Spinal cord hemisection also caused traditional stable spines to become unstable and led the eliminated spines even more hard to recur especially in the ipsilateral cortex of the SCI group. In addition, it also made the new formed spines unstable.

[Treatment of clavicular fractures using intramedullary nailing or K-wire versus plating fixation: a meta-analysis].

OBJECTIVE: TFo compare the efficacy and complications rate of intramedullary (IM) nailing or K-wire versus plating fixation for clavicular fractures. METHODS: Pubmed, Embase, Cochrane Library databases, CNKI, VIP and Wangfang databases were searched to find all randomized or quasi-randomized controlled trials of clavicle fractures using plating versus IM nailing or K-wire. The methodologic quality of the studies was assessed. After independent study selection by 2 authors ,data were collected and extracted independently. Outcomes of postoperative shoulder functional measurement, the efficacy and information of the operation and complications rate were meta-analyzed using RevMan 5 software. RESULTS: Nine hundreds and seventy-six patients in 10 randomized controlled trials (RCTs) and 3 quasi-RCTs were involved in the meta-analysis,of which 5 studies compared the K-wire and the plating fixations and 8 studies compared the IM nailing and the plating fixations. The overall odds ratio(OR) (with 95% CI) of the operation efficacy for K-wire versus the plating was 3.79 (1.93, 7.46). The overall weighted mean difference (with 95% CI) of Constant Shoulder score for plating versus IM fixation was -1.39 (-3.43, 0.65) in 6 studies. The overall OR of the plating versus IM nailing was 9.34(2.70, 32.32) for the overall major complications in 5 studies and 5.04 (1.52,16.77) for the revision rate in 5 studies. CONCLUSION: The current limited evidences suggested that the IM fixation could reduce the incidences of the overall major complications and the revision surgery, while the post-operative efficacy of the plating was superior to the K-wire. More high quality RCTs are still needed in the future.