Electroacupuncture Relieves HuR/KLF9-Mediated Inflammation to Enhance Neurological Repair after Spinal Cord Injury.

Electroacupuncture (EA) is widely applied in clinical therapy for spinal cord injury (SCI). However, the associated molecular mechanism has yet to be elucidated. The current study aimed to investigate the underlying mechanism of EA in neurologic repair after SCI. First, we investigated the role of EA in the neurologic repair of the SCI rat model. The expression levels of human antigen R (HuR) and Krüppel-like factor 9 (KLF9) in spinal cord tissues were quantified after treatment. Second, we conducted bioinformatics analysis, RNA pull-down assays, RNA immunoprecipitation, and luciferase reporter gene assay to verify the binding of HuR and KLF9 mRNA for mRNA stability. Last, HuR inhibitor CMLD-2 was used to verify the enhanced effect of EA on neurologic repair after SCI via the HuR/KLF9 axis. Our data provided convincing evidence that EA facilitated the recovery of neuronal function in SCI rats by reducing apoptosis and inflammation of neurons. We found that EA significantly diminished the SCI-mediated upregulation of HuR, and HuR could bind to the 3' untranslated region of KLF9 mRNA to protect its decay. In addition, a series of in vivo experiments confirmed that CMLD-2 administration increased EA-mediated pain thresholds and motor function in SCI rats. Collectively, the present study showed that EA improved pain thresholds and motor function in SCI rats via impairment of HuR-mediated KLF9 mRNA stabilization, thus providing a better understanding of the regulatory mechanisms regarding EA-mediated neurologic repair after SCI.

A systematic review of the safety and efficacy on cognitive function of herbal and nutritional medicines in older adults with and without subjective cognitive impairment.

BACKGROUND: Subjective cognitive impairment (SCI) substantially increases dementia risk and is often conceptualised as the preclinical asymptomatic phase of the cognitive decline continuum. Due to the lack of pharmacological interventions available to treat SCI and reduce dementia risk, and the popularity of herbal and nutritional medicines, the primary aim of this review was to investigate the efficacy on cognitive function and safety of herbal and nutritional medicines (relative to a control) for older adults with and without SCI. The secondary aims were to describe the study characteristics and assess the methodological quality of included studies. METHOD: Five databases (Cochrane, MEDLINE, CINAHL, PsycInfo, and EMBASE) were searched from database inception with weekly alerts established until review finalisation on 18 September 2022. Articles were eligible if they included the following: study population of older adults with and without SCI, herbal and nutritional medicines as an intervention, evaluated cognitive outcomes and were randomised control trials. RESULTS: Data were extracted from 21/7666 eligible full-text articles, and the risk of methodological bias was assessed (with SCI = 9/21; without SCI = 12/21). Most studies (20/21) employed parallel, randomised, placebo-controlled designs and were 12 weeks in length. Herbal supplements were widely used (17/21), namely a form of Ginkgo biloba (8/21) or Bacopa monnieri (6/21). Measures of cognition varied across studies, with 14/21 reporting improvements in at least one domain of cognitive functioning over time, in the intervention group (compared to control). A total of 14/21 studies were deemed as having an overall high methodological risk of bias, 6/21 had some concerns, and only one study (using an SCI population) was assessed as having a low risk of methodological bias. CONCLUSIONS: Overall, this review found that there is a low quality of evidence regarding the efficacy of cognitive function and safety of herbal and nutritional medicines for older adults with and without SCI, due to a high risk of bias across studies. Additionally, further work needs to be done in classifying and understanding SCI and selecting appropriate trial primary outcomes before future studies can more accurately determine the efficacy of interventions for this population.

Identification of canonical pyroptosis-related genes, associated regulation axis, and related traditional Chinese medicine in spinal cord injury.

Neuroinflammation plays an important role in spinal cord injury (SCI), and pyroptosis is inflammatory-related programmed cell death. Although neuroinflammation induced by pyroptosis has been reported in SCI, there is a lack of systematic research on SCI pyroptosis and its regulation mechanism. The purpose of this study was to systematically analyze the expression of pyroptosis-related genes (PRGs) in different SCI models and associated regulation axis by bioinformatics methods. We downloaded raw counts data of seven high-throughput sequencings and two microarray datasets from the GEO database, classified by species (rat and mouse) and SCI modes (moderate contusive model, aneurysm clip impact-compression model, and hemisection model), including mRNAs, miRNAs, lncRNAs, and circRNAs, basically covering the acute, subacute and chronic stages of SCI. We performed differential analysis by R (DEseq2) or GEO2R and found that the AIM2/NLRC4/NLRP3 inflammasome-related genes, GSDMD, IL1B, and IL18, were highly expressed in SCI. Based on the canonical NLRP3 inflammasome-mediated pyroptosis-related genes (NLRP3/PRGs), we constructed transcription factors (TFs)-NLRP3/PRGs, miRNAs- Nlrp3/PRGs and lncRNAs/circRNAs/mRNAs-miRNA- Nlrp3/PRGs (ceRNA) networks. In addition, we also predicted Traditional Chinese medicine (TCM) and small, drug-like molecules with NLRP3/PRGs as potential targets. Finally, 39 up-regulated TFs were identified, which may regulate at least two of NLRP3/PRGs. A total of 7 down-regulated miRNAs were identified which could regulate Nlrp3/PRGs. ceRNA networks were constructed including 23 lncRNAs, 3 cicrRNAs, 6 mRNAs, and 44 miRNAs. A total of 24 herbs were identified which may with two NLRP3/PRGs as potential targets. It is expected to provide new ideas and therapeutic targets for the treatment of SCI.

ICEP: An Instrumented Cycling Ergometer Platform for the Assessment of Advanced FES Strategies.

BACKGROUND: Functional electrical stimulation (FES) cycling has seen an upsurge in interest over the last decade. The present study describes the novel instrumented cycling ergometer platform designed to assess the efficiency of electrical stimulation strategies. The capabilities of the platform are showcased in an example determining the adequate stimulation patterns for reproducing a cycling movement of the paralyzed legs of a spinal cord injury (SCI) subject. METHODS: Two procedures have been followed to determine the stimulation patterns: (1) using the EMG recordings of the able-bodied subject; (2) using the recordings of the forces produced by the SCI subject's stimulated muscles. RESULTS: the stimulation pattern derived from the SCI subject's force output was found to produce 14% more power than the EMG-derived stimulation pattern. CONCLUSIONS: the cycling platform proved useful for determining and assessing stimulation patterns, and it can be used to further investigate advanced stimulation strategies.

Formononetin Inhibits Microglial Inflammatory Response and Contributes to Spinal Cord Injury Repair by Targeting the EGFR/MAPK Pathway.

Zhenbao Pill contains many Chinese herbal medicinal ingredients and has been proven to have therapeutic effects on the repair of spinal cord injury (SCI). This study attempts to investigate the role of formononetin (FMN), an ingredient of Zhenbao Pill, in regulating neuroinflammation after SCI and the underlying mechanism. Primary microglia isolated from the spinal cord of newborn rats and human microglial clone 3 (HMC3) cells were stimulated with IL-1ß followed by FMN incubation. The cell viability and inflammatory cytokine levels were detected. The target of FMN was predicted and screened using databases. By silencing or overexpression of epidermal growth factor receptor (EGFR), the anti-neuroinflammatory effect of FMN was assessed in vitro. In vivo, FMN was intraperitoneally injected into rats after SCI followed by the neurological function and histopathology examination. The isolated microglia were in high purity, and the different concentrations of FMN incubation had no toxic effects on primary microglia and HMC3 cells. FMN reduced the inflammatory cytokine levels (TNF-α and IL-6) in a concentration-dependent manner. EGFR silencing or FMN incubation decreased p-EGFR and p-p38 levels and down-regulated inflammatory cytokine levels in IL-1ß-stimulated cells or supernatants. Nevertheless, the effects of FMN on microglial inflammation were reversed by EGFR overexpression. In vivo, FMN treatment improved the neuromotor function, repaired tissue injury, and inhibited EGFR/p38MAPK phosphorylation. Formononetin inhibits microglial inflammatory response and contributes to SCI repair via the EGFR/p38MAPK signaling pathway.

Paving the way for a better management of pain in patients with spinal cord injury: An exploratory study on the use of Functional Electric Stimulation(FES)-cycling.

CONTEXT/OBJECTIVE: Chronic pain is common in patients with spinal cord injury (SCI), for whom it negatively affects quality of life, and its treatment requires an integrated approach. To this end, lower limb functional electrical stimulation (FES) cycling holds promise. OBJECTIVE: To investigate pain reduction in a sample of patients with SCI by means of lower limb rehabilitation using FES cycling. DESIGN, SETTING AND PARTICIPANTS: Sixteen patients with incomplete and complete SCIs, attending the Neurorobotic Unit of our research institute and reporting pain at or below the level of their SCI were recruited to this exploratory study. INTERVENTIONS: Patients undertook two daily sessions of FES cycling, six times weekly, for 6 weeks. OUTCOME MEASURES: Pain outcomes were measured using the 0-10 numerical rating scale (NRS), the Multidimensional Pain Inventory for SCI (MPI-SCI), and the 36-Item Short Form Survey (SF-36). Finally, we assessed the features of dorsal laser-evoked potentials (LEPs) to objectively evaluate Aδ fiber pathways. RESULTS: All participants tolerated the intervention well, and completed the training without side effects. Statistically significant changes were found in pain-NRS, MPI-SCI, and SF-36 scores, and LEP amplitudes. Following treatment, we found that three patients experienced high pain relief (an NRS decrease of at least 80%), six individuals achieved moderate pain relief (an NRS decrease of about 30-70%), and five participants had mild pain relief (an NRS decrease of less than 30%). CONCLUSION: Our preliminary results suggest that FES cycling training is capable of reducing the pain reported by patients with SCI, regardless of American Spinal Injury Association scoring, pain level, or the neurological level of injury. The neurophysiological mechanisms underlying such effects are likely to be both spinal and supraspinal.

Buyang Huanwu decoction improves neural recovery after spinal cord injury in rats through the mTOR signaling pathway and autophagy.

BACKGROUND: Spinal cord injury (SCI) refers to the interruption of the tracts inside the spinal cord caused by various factors. The repair of damaged axons has always been a difficult point in clinical treatment and neuroscience research. The treatment of SCI with Buyang huanwu decoction (BYHWD), a well-known recipe for invigorating Qi (a vital force forming part of any living entity in traditional Chinese culture) and promoting blood circulation, shows a good effect. METHODS: The rubrospinal tract (RST) transection model in rats was established in this study and rats were administrated with low (BL), medium (BM), or high (BH) doses of BYHWD. RESULTS: Compared with the SCI group, BL, BM moderately, and BH significantly improved the motor function of forelimbs and increased the number of red nucleus neurons in SCI rats. As for the possible molecular mechanism, BL, BM moderately, and BH significantly increased mTOR whereas decreased Beclin-1 and LC3 in the red nucleus. CONCLUSION: In conclusion, low, medium, and high doses of BYHWD could promote neural recovery in SCI rats through improving motor function and neuron survival in the red nucleus. The neuroprotective effects of BYHWD might be associated with affecting the mTOR signaling pathway and autophagy.

Bioactive role of vitamins as a key modulator of oxidative stress, cellular damage and comorbidities associated with spinal cord injury (SCI).

Introduction: Spinal cord injury (SCI) cause significant disability and impact the quality of life of those affected by it. The nutritional status and diet are fundamental to diminish the progression of complications; vitamins modulate the inflammatory response and oxidative stress, promote blood-spinal cord barrier preservation and the prompt recovery of homeostasis. A deep knowledge of the benefits achieved from vitamins in patients with SCI are summarized. Information of dosage, time, and effects of vitamins in these patients are also displayed. Vitamins have been extensively investigated; however, more clinical trials are needed to clarify the scope of vitamin supplementation.Objective: The objective of this review was to offer relevant therapeutic information based on vitamins supplementation for SCI patients.Methods: Basic and clinical studies that have implemented the use of vitamins in SCI were considered. They were selected from the year 2000-2022 from three databases: PubMed, Science Direct and Google Scholar.Results: Consistent benefits in clinical trials were shown in those who were supplemented with vitamin D (prevents osteoporosis and improves physical performance variables), B3 (improves lipid profile) and B12 (neurological prophylaxis of chronic SCI damage) mainly. On the other hand, improvement related to neuroprotection, damage modulation (vitamin A) and its prophylaxis were associated to B complex vitamins supplementation; the studies who reported positive results are displayed in this review.Discussion: Physicians should become familiar with relevant information that can support conventional treatment in patients with SCI, such as the use of vitamins, a viable option that can improve outcomes in patients with this condition.

Handcycling with concurrent lower body low-frequency electromyostimulation significantly increases acute oxygen uptake: implications for rehabilitation and prevention.

Background: Acute increases in exercise-induced oxygen uptake (V̇O2) is crucial for aerobic training adaptations and depends on how much muscle mass is involved during exercising. Thus, handcycling is per se limited for higher maximal oxygen uptakes (V̇O2max) due to restricted muscle involvement. Handcycling with additional and simultaneous application of low-frequency electromyostimulation (EMS) to the lower extremities might be a promising stimulus to improve aerobic capacity in disabled and rehabilitative populations. Method: Twenty-six healthy young adults (13 female, age: 23.4 ± 4.5 years, height: 1.77 ± 0.09 m, mass: 71.7 ± 16.7 kg) completed 4 ×10 minutes of sitting (SIT), sitting with concurrent EMS (EMS_SIT), handcycling (60 rpm, 1/2 bodyweight as resistance in watts) (HANDCYCLE) and handcycling with concurrent EMS of the lower extremities (EMS_HANDCYCLE). During EMS_SIT and EMS_HANDCYCLE, low frequency EMS (impulse frequency: 4Hz, impulse width: 350 µs, continuous stimulation) was applied to gluteal, quadriceps and calf muscles. The stimulation intensity was selected so that the perceived pain could be sustained for a duration of 10 minutes (gluteus: 80.0 ± 22.7 mA, quadriceps: 94.5 ± 20.5 mA, calves: 77.5 ± 19.1 mA). Results: Significant mode-dependent changes of V̇O2 were found (p < 0.001, η p 2 = 0.852). Subsequent post-hoc testing indicated significant difference between SIT vs. EMS_SIT (4.70 ± 0.75 vs. 10.61 ± 4.28 ml min-1 kg-1, p < 0.001), EMS_SIT vs. HANDCYCLE (10.61 ± 4.28 vs. 13.52 ± 1.40 ml min-1 kg-1, p = 0.005), and between HANDCYCLE vs. EMS_HANDCYCLE (13.52 ± 1.40 vs. 18.98 ± 4.89 ml min-1 kg-1, p = 0.001). Conclusion: Handcycling with simultaneous lower body low-frequency EMS application elicits notably higher oxygen uptake during rest and moderately loaded handcycling and may serve as an additional cardiocirculatory training stimuli for improvements in aerobic capacity in wheelchair and rehabilitation settings.

Electroacupuncture Inhibits NLRP3 Activation by Regulating CMPK2 After Spinal Cord Injury.

Objectives: This study aimed to evaluate the expression of cytosine monophosphate kinase 2 (CMPK2) and activation of the NLRP3 inflammasome in rats with spinal cord injury (SCI) and to characterize the effects of electroacupuncture on CMPK2-associated regulation of the NLRP3 inflammasome. Methods: An SCI model was established in Sprague-Dawley (SD) rats. The expression levels of NLRP3 and CMPK2 were measured at different time points following induction of SCI. The rats were randomly divided into a sham group (Sham), a model group (Model), an electroacupuncture group (EA), an adeno-associated virus (AAV) CMPK2 group, and an AAV NC group. Electroacupuncture was performed at jiaji points on both sides of T9 and T11 for 20 min each day for 3 consecutive days. In the AAV CMPK2 and AAV NC groups, the viruses were injected into the T9 spinal cord via a microneedle using a microscope and a stereotactic syringe. The Basso-Beattie-Bresnahan (BBB) score was used to evaluate the motor function of rats in each group. Histopathological changes in spinal cord tissue were detected using H&E staining, and the expression levels of NLRP3, CMPK2, ASC, caspase-1, IL-18, and IL-1ß were quantified using Western blotting (WB), immunofluorescence (IF), and RT-PCR. Results: The expression levels of NLRP3 and CMPK2 in the spinal cords of the model group were significantly increased at day 1 compared with those in the sham group (p < 0.05). The expression levels of NLRP3 and CMPK2 decreased gradually over time and remained low at 14 days post-SCI. We successfully constructed AAV CMPK2 and showed that CMPK2 was significantly knocked down following 2 dilutions. Finally, treatment with EA or AAV CMPK2 resulted in significantly increased BBB scores compared to those in the model group and the AAV NC group (p < 0.05). The histomorphology of the spinal cord in the EA and AAV CMPK2 groups was significantly different than that in the model and AAV NC groups. WB, IF, and PCR analyses showed that the expression levels of CMPK2, NLRP3, ASC, caspase-1, IL-18, and IL-1ß were significantly lower in the EA and AAV CMPK2 groups compared with those in the model and AAV NC groups (p < 0.05). Conclusion: Our study showed that CMPK2 regulated NLRP3 expression in rats with SCI. Activation of NLRP3 is a critical mechanism of inflammasome activation and the inflammatory response following SCI. Electroacupuncture downregulated the expression of CMPK2 and inhibited activation of NLRP3, which could improve motor function in rats with SCI.

Electroacupuncture promotes nerve regeneration and functional recovery in rats with spinal cord contusion through the coordinate interaction of CD4 and BDNF.

To explore the effect of electroacupuncture on spinal cord injury (SCI) involving immune-related factors and regeneration-related factors in rats. The model of spinal cord contusion was established by PCI 3000 instrument. Two types of acupuncture points were selected for electroacupuncture treatment on rats. The rats were tested once a week, and the fiber remodeling was detected by magnetic resonance imaging. Transcriptome sequencing was performed on spinal scar samples. Using Python to write code, statistical analysis and bioinformatics analysis of the correlation between transcriptome sequencing data and fiber reconstruction results are carried out. Lastly, the expression of CD4 and brain-derived neurotrophic factor (BDNF) in spinal cord scar was verified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Electroacupuncture exhibited a positive effect on the recovery of motor function in rats after SCI. Bioinformatics analysis found a direct interaction between CD4 and BDNF. Transcriptome sequencing and PCR results verified that electroacupuncture significantly reduced the expression of CD4, and increased significantly the expression of BDNF, simultaneously corresponding to nerve regeneration in rats with SCI. Our results showed that electroacupuncture intervention in SCI rats improves neural behavior via inhibiting the expression of CD4 and increasing the expression of BDNF.

mTOR pathway: A potential therapeutic target for spinal cord injury.

Spinal cord injury (SCI) is the most common disabling spinal injury, and the complex pathological process can eventually lead to severe neurological dysfunction. Many studies have reported that the mammalian target of rapamycin (mTOR) signaling pathway plays an important role in synaptogenesis, neuron growth, differentiation, and survival after central nervous system injury. It is also involved in various traumatic and central nervous system diseases, including traumatic brain injury, neonatal hypoxic-ischemic brain injury, Alzheimer's disease, Parkinson's disease, and cerebral apoplexy. mTOR has also been reported to play an important regulatory role in various pathophysiological processes following SCI. Activation of mTOR signals after SCI can regulate physiological and pathological processes, such as proliferation and differentiation of neural stem cells, regeneration of nerve axons, neuroinflammation, and glial scar formation, through various pathways. Inhibition of mTOR activity has been confirmed to promote repair in SCI. At present, many studies have reported that Chinese herbal medicine can inhibit the SCI-activated mTOR pathway to improve the microenvironment and promote nerve repair after SCI. Due to the role of the mTOR pathway in SCI, it may be a potential therapeutic target for SCI. This review is focused on the pathophysiological process of SCI, characteristics of the mTOR pathway, role of the mTOR pathway in SCI, role of inhibition of mTOR on SCI, and role and significance of inhibition of mTOR by related Chinese herbal medicine inhibitors in SCI. In addition, the review discusses the deficiencies and solutions to mTOR and SCI research shortcomings. This study hopes to provide reference for mTOR and SCI research and a theoretical basis for SCI biotherapy.

[Global centennial research and the internationalization of acupuncture and moxibustion: in the perspective of SCI database (1921-2020)].

The paper retrieves and analyzes SCI articles on acupuncture-moxibustion published in the world from 1921 to 2020. It is found that the overall growth of SCI articles on acupuncture-moxibustion in both China and global countries is increasing, and the proportion of publication amount in China is increased gradually. It is believed that the articles on acupuncture-moxibustion researches from 1921 to 2020 in the world collected in SCI database indicate three stages, i.e. scattered publication, internationalization and great contribution on acupuncture-moxibustion in TCM. The paper investigates the first SCI article on acupuncture-moxibustion in the world and in China respectively and analyzes the main disciplines, research institutions and journal distribution, as well as the highly cited articles in the global countries. It is proposed that acupuncture-moxibustion research in China should reflect the academic ideological characteristics of acupuncture-moxibustion in TCM, develop the interdisciplinary research and deepen the cooperation with high-level scientific institutions so as to improve the international academic influence of acupuncture-moxibustion in TCM.

The mechanisms of Chuanxiong Rhizoma in treating spinal cord injury based on network pharmacology and experimental verification.

BACKGROUND: Chuanxiong Rhizoma (CR) is a common traditional Chinese medicine (TCM) that has been widely used in the treatment of spinal cord injury (SCI). However, the underlying molecular mechanism of CR is still largely unknown. This study was designed to explore the bioactive components and the mechanism of CR in treating SCI based on a network pharmacology approach and experimental validation. METHODS: First, the active compounds and related target genes in CR were screened from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Subsequently, the corresponding target genes of SCI were collected by the Therapeutic Target Database (TTD) and GeneCards database. A protein-protein interaction (PPI) network was constructed using the STRING database. Furthermore, GO function and KEGG enrichment analysis of the targets were analyzed using DAVID tools. Subsequently, the AutoDock software for molecular docking was adopted to verify the above network pharmacology analysis results between the active components and key targets. Finally, an SCI rat model animal validation experiment was assessed to verify the reliability of the network pharmacology results. RESULTS: There were 7 active ingredients identified in CR and 246 SCI-related targets were collected. Then, 4 core nodes (ALB, AKT1, MAPK1, and EGFR) were discerned via construction of a PPI network of 111 common targets. The KEGG enrichment analysis results indicated that the Ras signaling pathway, estrogen signaling pathway, and vascular endothelial growth factor (VEGF) signaling pathway were enriched in the development of SCI. The results of molecular docking demonstrated that the effects of CR have a strong affinity with the 4 pivotal targets. Experimental validation in a rat model showed that CR could effectively improve the recovery of motor function and mechanical pain threshold after SCI. CONCLUSIONS: In summary, it revealed the mechanism of CR treatment for SCI involve active ingredients, targets and signaling pathways, providing a scientific basis for future investigations into the mechanism underlying CR treating for SCI.

Electroacupuncture promotes the recovery of rats with spinal cord injury by suppressing the Notch signaling pathway via the H19/EZH2 axis.

BACKGROUND: Spinal cord injury (SCI) is a life-changing event with an extremely poor prognosis. In our preliminary studies, electroacupuncture (EA) was found to promote the repair of SCI, which was closely related to the Notch signaling pathway. Therefore, in the present study, we hypothesized that EA protects against SCI by inhibiting the Notch signaling pathway and sought to investigate the underlying molecular mechanisms. METHODS: Rat and cell models of SCI were established. The expression of long non-coding RNA H19 was measured by real-time quantitative polymerase chain reaction. The expression levels of EZH2, Notch1, Notch3, Notch4, Hes1, and PS1 protein were measured by western blot. Cell apoptosis and viability were analyzed using flow cytometry and Cell Counting Kit-8 assays, respectively. The expressions of glial fibrillary acidic protein (GFAP) and nestin were detected by immunofluorescence staining. RESULTS: The expressions of H19, EZH2, and GFAP were significantly increased after SCI but were inhibited by EA; in contrast, nestin expression was significantly decreased by SCI but was restored by EA. Moreover, oxygen-glucose deprivation (OGD) treatment elevated the expression of H19, EZH2, and Notch-related factors as well as apoptosis in PC-12 cells, while suppressing cell viability. Suppressing H19 alleviated the effects of OGD on cell viability and apoptosis, and inhibited the expression of EZH2 and Notch-related factors expression; these effects were reversed by EZH2 overexpression. Finally, EA promoted the recovery of SCI rats and neural stem cell (NSC) proliferation by inhibiting the Notch signaling pathway, which was reversed by H19 overexpression. CONCLUSIONS: Our results demonstrated that EA promotes the recovery of SCI rats and increases the proliferation and differentiation of NSCs by suppressing the Notch signaling pathway via modulating the H19/EZH2 axis.

Effects of hyperbaric oxygen therapy on patients with spinal cord injury: A systematic review and meta-analysis of Randomized Controlled Trials.

BACKGROUND: The effects of hyperbaric oxygen therapy (HBO) for spinal cord injury (SCI) are controversial. OBJECTIVE: The purpose of this study was to evaluate the effects of HBO therapy on motor function, sensory function, and psychology after SCI. METHOD: We searched the following databases: Medline, Embase, PubMed, Ovid, Cochrane library, China National Knowledge Infrastructure (CNKI), Wan Fang, and VIP up to May 2020. We included Randomized Controlled Trials (RCTs) which investigated patients with SCI received HBO during hospitalization. Motor function, sensory function, and psychology status were measured by commonly used scales including American Spinal Injury Association (ASIA) motor score, Modified Barthel Index (MBI), ASIA sensory score, Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA). We performed a meta-analysis by calculating mean difference (MD) to determine the effect of HBO on three levels of function on patients with SCI. We evaluated heterogeneity by I2 test, and I2> 50% was significant. RESULTS: A total of 1746 studies were identified initially, and 11 studies were included, involving 875 participants. HBO therapy significantly improved the ASIA motor score (MD 15.84, 95% CI 9.04 to 22.64, I2= 87%). Six trails suggested that HBO therapy statistically promoted ASIA sensory score (MD 66.30, 95% CI 53.44 to 79.16, I2= 95%). The other four trails suggested that HBO therapy statistically increased the light touch score (MD 9.27, 95% CI 3.89 to 14.65, I2= 91%) and needling score (MD 10.01, 95% CI 8.60 to 11.43, I2= 95%), respectively. HBO therapy was implicated in the significant improvement of MBI (MD 13.80, 95% CI 10.65 to 16.94, I2= 0%). HBO therapy also decreased the HAMA (MD -2.37, 95% CI -2.72 to -2.02, I2= 0%) and HAMD (MD -3.74, 95% CI -5.82 to -1.65, I2= 90%). CONCLUSIONS: HBO therapy may improve motor function, sensory function and psychology after SCI compared to conventional treatments. More high-quality, large sample size RCTs are needed to support these perspectives.

Histopathological Evaluation of Spinal Cord with Experimental Traumatic Injury Following Implantation of a Controlled Released Drug Delivery System of Chitosan Hydrogel Loaded with Selenium Nanoparticle.

The purpose of this study was to evaluate the neuroprotective effect of local implantation of a controlled delivery system of chitosan hydrogel loaded with selenium nanoparticles in rats with spinal cord injury (SCI). For this purpose, 60 adult female rats were randomly divided into three equal groups. In all three groups, SCI was induced by aneurysm clamping at the level of thoracic vertebrae under inhaled anesthesia with isoflurane. In one group after spinal cord injury, chitosan hydrogels loaded with selenium nanoparticles (treatment group), and in the other group, only chitosan hydrogels (positive control group) were placed at the site of injury. In the last group (negative control), no material was placed in the injury site. Hematoxylin-eosin and glial fibrillary acidic protein (GFAP) staining evaluated histological changes at the site of injury on days 3, 7, 21, and 28 after surgery. Evaluations show that hemorrhage and inflammation also have a marked decrease in inflammatory cells at different times in the treatment group. This decrease was also seen in the chitosan group but was less severe than in the treatment group. The formation of nerve fibers was also observed in the treatment group over time of injury. Immunohistochemical studies of damaged tissue showed higher expression of GFAP protein in the astrocytes of the treatment group than in the other two groups and the chitosan group compared with the negative control group. A controlled drug delivery system containing selenium nanoparticles seems to play a role in the protection of nerve cells through its anti-inflammatory effect.

The mechanism of electroacupuncture for treating spinal cord injury rats by mediating Rho/Rho-associated kinase signaling pathway.

Objective: To determine the changes of gene and protein expression through Rho/ROCK signaling pathway in EA treated spinal cord injury (SCI) rats and to unveil the possible underlying mechanism.Design: Animal study.Setting: Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine.Participants: Eighty Male Sprague Dawley rats.Interventions: Electroacupuncture at Yaoyangguan (GV3), Dazhui (GV14), Zusanli (ST36) and Ciliao (BL32) and/or blocking agent Y27632 treatment.Outcome Measures: Protein expression was detected by ELISA and Western blotting, mRNA expression was detected by quantitative PCR and in situ hybridization. Morphological changes in spinal cord were evaluated by HE-staining and Nissl staining. Hindlimb motor function in the rats was evaluated by Basso-Beattie-Bresnahan (BBB) assessment methods.Results: Compared with injured rats in SCI group, EA, blocking agent Y27632 and EA + blocking agent Y27632 treatment had significantly reduced mRNA and protein expression levels of RhoA and ROCKII, decreased p-MLC protein expression and p-MLC/MLC ratio, suppressed cPLA2 activity and PGE2 level, improved spinal cord tissue morphology and BBB score of lower limb movement function at 7 days and at 14 days (P < 0.01 or <0.05).Conclusion: Similar to the blocking agent Y27632, EA may have a notable inhibitory effect on the Rho/ROCK signaling pathway after SCI, therefore reducing the inhibition of axonal growth and inflammatory reaction may be a key mechanism of EA treatment for SCI.

Global centennial research and the internationalization of acupuncture and moxibustion: in the perspective of SCI database (1921-2020) / 中国针灸

The paper retrieves and analyzes SCI articles on acupuncture-moxibustion published in the world from 1921 to 2020. It is found that the overall growth of SCI articles on acupuncture-moxibustion in both China and global countries is increasing, and the proportion of publication amount in China is increased gradually. It is believed that the articles on acupuncture-moxibustion researches from 1921 to 2020 in the world collected in SCI database indicate three stages, i.e. scattered publication, internationalization and great contribution on acupuncture-moxibustion in TCM. The paper investigates the first SCI article on acupuncture-moxibustion in the world and in China respectively and analyzes the main disciplines, research institutions and journal distribution, as well as the highly cited articles in the global countries. It is proposed that acupuncture-moxibustion research in China should reflect the academic ideological characteristics of acupuncture-moxibustion in TCM, develop the interdisciplinary research and deepen the cooperation with high-level scientific institutions so as to improve the international academic influence of acupuncture-moxibustion in TCM.