Regulation of "Right Ankle Dorsiflexion" Motor Imagery on Brain Function of Spinal Cord Injury: A FOCA-Based Prospective Study.

BACKGROUND: Motor dysfunction is the main functional disability after spinal cord injury (SCI), seriously affecting the life and work of patients. In addition to spinal cord damage, the brain undergoes structural and functional plastic changes. This study explored brain function remodeling in patients with SCI and the effect of right ankle dorsiflexion motor imagery task on brain function. METHODS: This prospective study enrolled 11 patients with SCI and dyskinesia of the right lower limb and 12 healthy subjects at the General Hospital of Western Theater Command PLA (January 2015 to December 2016). They underwent functional magnetic resonance imaging (fMRI) in the resting state and the "right ankle dorsiflexion" motor imagery task state. Four-dimensional (spatiotemporal) concordance (FOCA) of local neuronal activity was used for fMRI image analysis. The differences between SCI patients and healthy subjects were compared using the two-sample t-test. RESULTS: In the resting state, compared with healthy subjects, patients with SCI showed decreased FOCA in the left putamen, right caudate nucleus, and right superior occipital gyrus and increased FOCA in the left precentral gyrus. In the right ankle dorsiflexion motor imagery task state, FOCAs in the right inferior temporal gyrus and left inferior parietal lobule were decreased in patients with SCI. CONCLUSIONS: After SCI, a series of changes in the structure and function of the brain occur. Research on brain plasticity after SCI might help explore the central mechanisms underlying functional recovery after treatments, providing more therapeutic strategies for SCI.

Modulatory effects of gut microbiota on innate and adaptive immune responses following spinal cord injury.

Spinal cord injury (SCI) represents a highly debilitating trauma to the central nervous system, currently lacking effective therapeutic strategies. The cascade of inflammatory responses induced by secondary damage following SCI disrupts the local immune environment at the injury site, ultimately exacerbating functional impairments post-injury. With advancing research on the gut-brain axis, evidence suggests that dysbiosis of the gut microbiota post-SCI amplifies inflammatory responses and plays a pivotal role in modulating post-injury immune-inflammatory responses. In this review article, we will explore the significant role of the gut microbiota and its metabolic products in modulating the responses of central and peripheral immune cells post-SCI, as well as their potential as therapeutic interventions for SCI treatment.

Tauroursodeoxycholic acid: a bile acid that may be used for the prevention and treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disease that has become one of the main factors affecting human health. It has serious impacts on individuals, families, and society. With the development of population aging, the incidence of AD will further increase worldwide. Emerging evidence suggests that many physiological metabolic processes, such as lipid metabolism, are implicated in the pathogenesis of AD. Bile acids, as the main undertakers of lipid metabolism, play an important role in the occurrence and development of Alzheimer's disease. Tauroursodeoxycholic acid, an endogenous bile acid, has been proven to possess therapeutic effects in different neurodegenerative diseases, including Alzheimer's disease. This review tries to find the relationship between bile acid metabolism and AD, as well as explore the therapeutic potential of bile acid taurocursodeoxycholic acid for this disease. The potential mechanisms of taurocursodeoxycholic acid may include reducing the deposition of Amyloid-ß protein, regulating apoptotic pathways, preventing tau hyperphosphorylation and aggregation, protecting neuronal synapses, exhibiting anti-inflammatory properties, and improving metabolic disorders. The objective of this study is to shed light on the use of tauroursodeoxycholic acid preparations in the prevention and treatment of AD, with the aim of identifying effective treatment targets and clarifying various treatment mechanisms involved in this disease.

Every-other-day fasting inhibits pyroptosis while regulating bile acid metabolism and activating TGR5 signaling in spinal cord injury.

Every-other-day fasting (EODF) is a form of caloric restriction that alternates between periods of normal eating and fasting, aimed at preventing and treating diseases. This approach has gained widespread usage in basic research on neurological conditions, including spinal cord injury, and has demonstrated significant neuroprotective effects. Additionally, EODF is noted for its safety and feasibility, suggesting broad potential for application. This study aims to evaluate the therapeutic effects of EODF on spinal cord injury and to investigate and enhance its underlying mechanisms. Initially, the SCI rat model was utilized to evaluate the effects of EODF on pathological injury and motor function. Subsequently, considering the enhancement of metabolism through EODF, bile acid metabolism in SCI rats was analyzed using liquid chromatography-mass spectrometry (LC-MS), and the expression of the bile acid receptor TGR5 was further assessed. Ultimately, it was confirmed that EODF influences the activation of microglia and NLRP3 inflammasomes associated with the TGR5 signaling, along with the expression of downstream pyroptosis pathway related proteins and inflammatory cytokines, as evidenced by the activation of the NLRP3/Caspase-1/GSDMD pyroptosis pathway in SCI rats. The results demonstrated that EODF significantly enhanced the recovery of motor function and reduced pathological damage in SCI rats while controlling weight gain. Notably, EODF promoted the secretion of bile acid metabolites, activated TGR5, and inhibited the NLRP3/Caspase-1/GSDMD pyroptosis pathway and inflammation in these rats. In summary, EODF could mitigate secondary injury after SCI and foster functional recovery by improving metabolism, activating the TGR5 signaling and inhibiting the NLRP3 pyroptosis pathway.

Effects of a lower limb walking exoskeleton on quality of life and activities of daily living in patients with complete spinal cord injury: A randomized controlled trial.

BACKGROUND: In recent years, lower limb walking exoskeletons have been widely used in the study of spinal cord injury (SCI). OBJECTIVE: To explore the effect of a lower limb walking exoskeleton on quality of life and functional independence in patients with motor complete SCI. METHODS: This was a multi-center, single blind, randomized controlled trial. A total of 16 SCI patients were randomly assigned to either the exoskeleton-assisted walking (EAW) group (n= 8) or the conventional group (n= 8). Both groups received conventional rehabilitation training, including aerobic exercise and strength training. The EAW group additionally conducted the exoskeleton-assisted walking training using an AIDER powered robotic exoskeleton for 40-50 minutes, 5 times/week for 8 weeks. World Health Organization quality of life-BREF (WHOQOL-BREF) and the Spinal Cord Independence Measure III (SCIM-III) were used for assessment before and after training. RESULTS: There was an increasing tendency of scores in the psychological health, physical health, and social relationships domain of WHOQOL-BREF in the EAW group after the intervention compared with the pre-intervention period, but there was no significant difference (P> 0.05). SCIM-III scores increased in both groups compared to pre-training, with only the conventional group showing a significant difference after 8 weeks of training (P< 0.05). CONCLUSION: A lower limb walking exoskeleton may have potential benefits for quality of life and activities of daily living in patients with motor complete SCI.

Effects of exoskeleton-assisted walking on bowel function in motor-complete spinal cord injury patients: involvement of the brain-gut axis, a pilot study.

Evidence has demonstrated that exoskeleton robots can improve intestinal function in patients with spinal cord injury (SCI). However, the underlying mechanisms remain unelucidated. This study investigated the effects of exoskeleton-assisted walking (EAW) on intestinal function and intestinal flora structure in T2-L1 motor complete paraplegia patients. The results showed that five participants in the EAW group and three in the conventional group reported improvements in at least one bowel management index, including an increased frequency of bowel evacuations, less time spent on bowel management per day, and less external assistance (manual digital stimulation, medication, and enema usage). After 8 weeks of training, the amount of glycerol used in the EAW group decreased significantly (p <0.05). The EAW group showed an increasing trend in the neurogenic bowel dysfunction (NBD) score after 8 weeks of training, while the conventional group showed a worsening trend. Patients who received the EAW intervention exhibited a decreased abundance of Bacteroidetes and Verrucomicrobia, while Firmicutes, Proteobacteria, and Actinobacteria were upregulated. In addition, there were decreases in the abundances of Bacteroides, Prevotella, Parabacteroides, Akkermansia, Blautia, Ruminococcus 2, and Megamonas. In contrast, Ruminococcus 1, Ruminococcaceae UCG002, Faecalibacterium, Dialister, Ralstonia, Escherichia-Shigella, and Bifidobacterium showed upregulation among the top 15 genera. The abundance of Ralstonia was significantly higher in the EAW group than in the conventional group, and Dialister increased significantly in EAW individuals at 8 weeks. This study suggests that EAW can improve intestinal function of SCI patients in a limited way, and may be associated with changes in the abundance of intestinal flora, especially an increase in beneficial bacteria. In the future, we need to further understand the changes in microbial groups caused by EAW training and all related impact mechanisms, especially intestinal flora metabolites. Clinical trial registration: https://www.chictr.org.cn/.

Bifidobacterium: a probiotic for the prevention and treatment of depression.

Depression is a common psychological disease, which has become one of the main factors affecting human health. It has a serious impact on individuals, families, and society. With the prevalence of COVID-19, the incidence of depression has further increased worldwide. It has been confirmed that probiotics play a role in preventing and treating depression. Especially, Bifidobacterium is the most widely used probiotic and has positive effects on the treatment of depression. The mechanisms underlying its antidepressant effects might include anti-inflammation and regulation of tryptophan metabolism, 5-hydroxytryptamine synthesis, and the hypothalamus-pituitary-adrenal axis. In this mini-review, the relationship between Bifidobacterium and depression was summarized. It is hoped that Bifidobacterium-related preparations would play a positive role in the prevention and treatment of depression in the future.

Gut microbiota and transcriptome dynamics in every-other-day fasting are associated with neuroprotection in rats with spinal cord injury.

Introduction: Every-other-day fasting (EODF) is a classical intermittent fasting (IF) mode with neuroprotective effects that promotes motor function recovery after spinal cord injury (SCI) in rats. However, its dynamic effects on the gut microbiota and spinal cord transcriptome remain unknown. Methods: In this study, 16S rRNA sequencing and RNA-seq analysis were used to investigate the effects of ad libitum (AL) and EODF dietary modes on the structural characteristics of rat gut microbiota in rats and the spinal cord transcriptome at various time points after SCI induction. Results: Our results showed that both dietary modes affected the bacterial community composition in SCI rats, with EODF treatment inducing and suppressing dynamic changes in the abundances of potentially anti-inflammatory and pro-inflammatory bacteria. Furthermore, the differentially expressed genes (DEGs) enriched after EODF intervention in SCI rats were associated with various biological events, including immune inflammatory response, cell differentiation, protein modification, neural growth, and apoptosis. In particular, significant spatiotemporal differences were apparent in the DEGs associated with neuroprotection between the EODF and AL interventions. These DGEs were mainly focused on days 1, 3, and 7 after SCI. The relative abundance of certain genera was significantly correlated with DEGs associated with neuroprotective effects in the EODF-SCI group. Discussion: Our results showed that EODF treatment may exert neuroprotective effects by modulating the transcriptome expression profile following SCI in rats. Furthermore, gut microbiota may be partially involved in mediating these effects.

Clinical studies on treatment of earthquake-caused posttraumatic stress disorder using electroacupuncture.

The objective of this study was to assess the efficacy and safety of electroacupuncture in 138 patients with earthquake-caused PTSD using Randomized Controlled Trials (RCTs). 138 cases enrolled were randomly assigned to an electro-acupuncture group and a paroxetine group. The electro-acupuncture group was treated by scalp electro-acupuncture on Baihui (GV 20), Sishencong (EX-HN 1), Shenting (GV 24), and Fengchi (GB 20), and the paroxetine group was treated with simple oral administration of paroxetine. The efficacy and safety of the electro-acupuncture on treatment of 69 PTSD patients were evaluated using Clinician-Administered PTSD Scale (CAPS), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Treatment Emergent Symptom Scale (TESS) according to clinical data. The total scores of CAPS, HAMD, and HAMA in the two groups after treatment showed significant efficacy compared to those before treatment. The comparison of reduction in the scores of CAPS, HAMD, and HAMA between the two groups suggested that the efficacy in the treated group was better than that in the paroxetine group. The present study suggested that the electro-acupuncture and paroxetine groups have significant changes in test PTSD, but the electro-acupuncture 2 group was more significant.

The effect of Iridoids effective fraction of Valeriana jatamansi Jones on movement function in rats after acute cord injury and the related mechanism.

OBJECTIVES: Spinal cord injury (SCI) is a disastrous central nervous system (CNS) disorder, which was intimately associated with oxidative stress. Studies have confirmed that Iridoids Effective Fraction of Valeriana jatamansi Jones (IEFV) can scavenge reactive oxygen species. This study aimed to confirm the efficacy of IEFV in ameliorating SCI. METHODS: For establish the SCI model, the Sprague-Dawley rats underwent a T10 laminectomy with transient violent oppression by aneurysm clip. Then, the rats received IEFV intragastrically for 8 consecutive weeks to evaluate the protective effect of IEFV on motor function, oxidative stress, inflammation and neurotrophic factors in SCI rats. RESULTS: Basso, Beattie and Bresnahan scores, hematoxylin and eosin (H&E) staining and transmission electron microscopy experiments found IEFV protected motor function and alleviated neuron damage. Meanwhile, IEFV treatment decreased the release of malondialdehyde, interleukin-6 (IL-6), cyclooxygenase-2 and tumor necrosis factor-α. Moreover, IEFV treatment elevated the expression levels of brain-derived neurotrophic factor and nerve growth factor of SCI rats. Finally, administration of IEFV significantly inhibited the expression of p-p65 and toll-like receptor 4 (TLR4). CONCLUSIONS: This study suggests that IEFV could attenuate the oxidative stress and inflammatory response of the spinal cord after SCI, which was associated with inhibition of the TLR4/nuclear factor-kappaB signaling pathway.

Relationship between gut microbiota and lymphocyte subsets in Chinese Han patients with spinal cord injury.

This study is to investigate the changes of lymphocyte subsets and the gut microbiota in Chinese Han patients with spinal cord injury (SCI). We enrolled 23 patients with SCI and 21 healthy controls. Blood and fecal samples were collected. The proportion of lymphocyte subsets was detected by flow cytometry. 16S rDNA sequencing of the V4 region was used to analyze the gut microbiota. The changes of the gut microbiota were analyzed by bioinformatics. Correlation analysis between gut microbiota and lymphocyte subsets was performed. CD4 + cells, CD4 + /CD8 + ratio and CD4 + CD8 + cells in peripheral blood of SCI patients were significantly lower than those of the control group (P < 0.05). There was no significant difference in B cells and CIK cells between the SCI group and the control group. The gut microbiota community diversity index of SCI patients was significantly higher than that of healthy controls. In SCI patients, the relative abundance of Lachnospiraceae (related to lymphocyte subset regulation), Ruminococcaceae (closely related to central nervous system diseases), and Escherichia-Shigella (closely related to intestinal infections) increased significantly, while the butyrate producing bacteria (Fusobacterium) that were beneficial to the gut were dramatically decreased. Correlation analysis showed that the five bacterial genera of SCI patients, including Lachnospiraceae UCG-008, Lachnoclostridium 12, Tyzzerella 3, Eubacterium eligens group, and Rumencocciucg-002, were correlated with T lymphocyte subsets and NK cells. In the SCI group, the flora Prevotella 9, Lachnospiraceae NC2004 group, Veillonella, and Sutterella were positively correlated with B cells. However, Fusobacterium and Akkermansia were negatively correlated with B cells. Moreover, Roseburia and Ruminococcaceae UCG-003 were positively correlated with CIK cells. Our results suggest that the gut microbiota of patients with SCI is associated with lymphocyte subsets. Therefore, it is possible to improve immune dysregulation in SCI patients by modulating gut microbiota, which may serve as a new therapeutic method for SCI.

Prevalence and risk factors of anxiety and depression among patients with breast cancer: a protocol for systematic review and meta-analysis.

BACKGROUND: Patients with breast cancer often experience severe psychological distress, especially anxiety and depression, leading to poorer quality of life, shortened survival time and increased mortality.The objective of the review will be to summarise data on the prevalence and risk factors of anxiety and depression in patients with breast cancer. METHODS AND ANALYSIS: Two reviewers will be applied in seven databases, including Web of Science, PubMed, EMBASE, Wan Fang Data Knowledge Service Platform, Chinese Biomedical Literature Database, Chinese Scientific Journal Database (VIP database), China National Knowledge Infrastructure and for studies on the prevalence and risk factors of depression in patients with breast cancer, which should be published from inception to Feb 2020 in English, Chinese, French and Spanish. The selection of studies, data extraction and risk of bias assessment will be done independently by two reviewers. Data synthesis will be carried out using RevMan V.5.3 software. The heterogeneity will be determined by the I² test. Publication bias will be evaluated by generating a funnel plot and performing the Begg and Egger test. The quality of the systematic review will be assessed using the Grading of Recommendations Assessment, Development and Evaluation Tool criteria. ETHICS AND DISSEMINATION: No ethical approval is required. This protocol will not involve individual patient information and endangering participant rights. The results will be reported in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/D6A4P.

Safety of Every-Other-Day Fasting in the Treatment of Spinal Cord Injury: A Randomized Controlled Trial.

ABSTRACT: Every-other-day fasting is effective for a variety of major human diseases, but the safety of these interventions is uncertain for patients with spinal cord injury. A randomized controlled study was conducted to investigate the safety of every-other-day fasting in patients with spinal cord injury. Participants who met the diagnostic inclusion and exclusion criteria were randomly divided into the control and every-other-day fasting groups. In the every-other-day fasting group, fasting lasted from 09:00 p.m. on day 1 to 06:00 p.m. on the following day (day 2). Dinner on day 2 was restricted to approximately 30% of the average daily calorie intake. The changes in plasma glucose were recorded daily for 2 days and every other day from the third day after every-other-day fasting intervention. The changes in albumin, prealbumin, plasma potassium, serum sodium, blood calcium, body weight, and body mass index were monitored at the baseline and at the end of the every-other-day fasting intervention. The results showed that compared with the control group, the mean blood glucose levels were significantly decreased from the second week after every-other-day fasting intervention. The body weight of patients in the every-other-day fasting group was notably reduced compared with that at baseline, whereas in body mass index, no obvious differences were observed before and after treatment with every-other-day fasting. In general, every-other-day fasting could be considered as a safe approach for individuals with spinal cord injury.

Acupoint catgut embedding for patients with migraine: A protocol for systematic review.

BACKGROUND: Nowadays, acupoint catgut embedding is being used widely in the treatment of migraine. So far, there is no a systematic review has been conducted. Therefore, the purpose of this paper is to systematically evaluate the efficacy and safety of acupoint catgut embedding on migraine. METHODS: We will search the following databases from their inception to May 2020: PubMed, Embase, Medline, EBSCO, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wan Fang Database, the Chongqing VIP Chinese Science and Technology Periodical Database, Cochrane Library. In addition, we will manually retrieve other resources including conference articles, and gray literature. The randomized controlled trials in English or Chinese associated with acupoint catgut embedding for migraines will be included. The data collection and analysis will be conducted independently by 2 reviewers. Meta-analysis will be performed using Rev Man V.5.3.5 statistical software. RESULTS: This study will provide a high-quality synthesis to evaluate the efficacy and safety of acupoint catgut embedding for patients with migraine. CONCLUSION: This systematic review will provide evidence to judge whether acupoint catgut embedding is an effective and safe intervention for patients with migraines. It will provide reliable evidence for its extensive application. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/RP9NW.

Scalp acupuncture for patients with vascular dementia: A protocol for systematic review and meta-analysis of randomized controlled trails.

BACKGROUND: Vascular dementia (VD) is a kind of acquired intelligence impairment syndrome caused by a series of cerebrovascular factors leading to brain tissue damage. Scalp acupuncture is widely used to treating VD. However, there is no a systematic review has been used to assess the efficacy and safety of scalp acupuncture therapy for VD. Therefore, the purpose of this paper is to systematically evaluate the effects of scalp acupuncture on VD. METHODS: We will search the following databases from their inception to July 2020: PubMed, Chinese National Knowledge Infrastructure (CNKI), Wan Fang Database, Embase, Medline, Chinese Biomedical Literature Database (CBM), EBSCO, Web of Science, Technology Periodical Database (VIP), the Chongqing VIP Chinese Science and Cochrane Library. At the same time, we will retrieve other resources including conference articles, and gray literature. The randomized controlled trials (RCTs) in English or Chinese associated with scalp acupuncture for VD will be included. Our study data collection and analysis will be conducted independently by 2 reviewers, and Rev Man V.5.3.5 statistical software will be used to performing meta-analysis. RESULTS: This review research will provide a high-quality synthesis to evaluate the efficacy and safety of scalp acupuncture for patients with VD. CONCLUSION: This study will provide available evidence to judge whether scalp acupuncture is an effective and safe intervention for patients with VD. It also will provide reliable evidence for its widespread application. ETHICS AND DISSEMINATION: This systematic review will provide convincing evidence for both patients and clinicians. It does not require ethical approval and the results will be published in a peer-reviewed journal. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/7CYZR.

Effects of repetitive magnetic stimulation on motor function and GAP43 and 5-HT expression in rats with spinal cord injury.

OBJECTIVES: Spinal cord injury (SCI) is a disabling central nervous system disorder. This study aimed to explore the effects of repetitive trans-spinal magnetic stimulation (rTSMS) of different spinal cord segments on movement function and growth-associated protein-43 (GAP43) and 5-hydroxytryptamine (5-HT) expression in rats after acute SCI and to preliminarily discuss the optimal rTSMS treatment site to provide a theoretical foundation and experimental evidence for clinical application of rTSMS in SCI. METHODS: A rat T10 laminectomy SCI model produced by transient application of an aneurysm clip was used in the study. The rats were divided into group A (sham surgery), group B (acute SCI without stimulation), group C (T6 segment stimulation), group D (T10 segment stimulation), and group E (L2 segment stimulation). RESULTS: In vivo magnetic stimulation protected motor function, alleviated myelin sheath damage, decreased NgR and Nogo-A expression levels, increased GAP43 and 5-HT expression levels, and inhibited terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and apoptosis-related protein expression in rats at 8 weeks after the surgery. CONCLUSIONS: This study suggests that rTSMS can promote GAP43 and 5-HT expression and axonal regeneration in the spinal cord, which is beneficial to motor function recovery after acute SCI.

[Effect on the activities of daily life of the patients with traumatic spinal cord injury treated by the paraplegia-triple-needling method].

OBJECTIVE: To compare the differences in the efficacy on traumatic spinal cord injury(SCI) in the thoracic and lumbar vertebra between the paraplegia-triple-needling method and the conventional acupuncture therapy. METHODS: The perspectively randomized controlled trial was adopted. Forty-eight cases of traumatic SCI in the thoracic and lumbar vertebra were randomized into an observation group and a control group, 24 cases in each one. The conventional rehabilitation training was applied in both groups. In addition, the paraplegia-triple-needling method was used in the observation group. In the treatment, acupuncture was applied to the points of the Governor Vessel and the Back-shu which, located two segments above and below the spinal injury plane separately. Acupuncture with the electric pulsing stimulation was applied to the motor points of the key muscles of the lower extremities. In the control group, the conventional acupuncture was applied to Huantiao (GB 30), Zusanli (ST 36), Xuanzhong (GB 39) and Sanyinjiao (SP 6). In each group, the treatment was given once a day, one month treatment made 1 session. Totally, 3 sessions of treatment were required. Before and after treatment, as well as in 1-month follow-up visit after treatment, the modified Barthel index (MBI) and the function comprehensive assessment (FCA) were adopted to assess the activities of daily life (ADL) and the comprehensive function of the patients. The score of MBI and FCA were taken as the double response variables to imitate the multilevel model. The changing tendency of MBI and FCA along with the time was observed in two groups. RESULTS: In the follow-up visit, MBI and FCA score were all improved as compared with those before treatment in two groups (all P < 0.05). There were no statistically significant differences in MBI and FCA score at any time point between two groups (all P > 0.05). In 4-month observation, there was a rising tendency with time in MBI and FAC scoe in both groups, which was roughly linear. As time went on, the increasing amplitude in the observation group was much bigger. It was explained that there was no difference in the short-term efficacy between two groups. However, the long-term efficacy in the observation group was much better. CONCLUSION: Both the paraplegia-triple-needling method and the conventional acupuncture therapy can improve the ADL and the comprehensive function of the patients with traumatic SCI of the thoracic and lumbar vertebra. Concerning the long-term efficacy, the paraplegia-triple-needling combined with the rehabilitation training achieves better result. This therapeutic program is safe and effective.