Combined use of CLP290 and bumetanide alleviates neuropathic pain and its mechanism after spinal cord injury in rats.

AIM: We aimed to explore whether the combination of CLP290 and bumetanide maximally improves neuropathic pain following spinal cord injury (SCI) and its possible molecular mechanism. METHODS: Rats were randomly divided into five groups: Sham, SCI + vehicle, SCI + CLP290, SCI + bumetanide, and SCI + combination (CLP290 + bumetanide). Drug administration commenced on the 7th day post-injury (7 dpi) and continued for 14 days. All rats underwent behavioral assessments for 56 days to comprehensively evaluate the effects of interventions on mechanical pain, thermal pain, cold pain, motor function, and other relevant parameters. Electrophysiological assessments, immunoblotting, and immunofluorescence detection were performed at different timepoints post-injury, with a specific focus on the expression and changes of KCC2 and NKCC1 proteins in the lumbar enlargement of the spinal cord. RESULTS: CLP290 and bumetanide alleviated SCI-associated hypersensitivity and locomotor function, with the combination providing enhanced recovery. The combined treatment group exhibited the most significant improvement in restoring Rate-Dependent Depression (RDD) levels. In the combined treatment group and the two individual drug administration groups, the upregulation of potassium chloride cotransporter 2 (K+-Cl-cotransporter 2, KCC2) expression and downregulation of sodium potassium chloride cotransporter 1 (Na+-K+-Cl-cotransporter 1, NKCC1) expression in the lumbar enlargement area resulted in a significant increase in the KCC2/NKCC1 ratio compared to the SCI + vehicle group, with the most pronounced improvement seen in the combined treatment group. Compared to the SCI + vehicle group, the SCI + bumetanide group showed no significant paw withdrawal thermal latency (PWTL) improvement at 21 and 35 dpi, but a notable enhancement at 56 dpi. In contrast, the SCI + CLP290 group significantly improved PWTL at 21 days, with non-significant changes at 35 and 56 days. At 21 dpi, KCC2 expression was marginally higher in monotherapy groups versus SCI + vehicle, but not significantly. At 56 dpi, only the SCI + bumetanide group showed a significant difference in KCC2 expression compared to the control group. CONCLUSION: Combined application of CLP290 and bumetanide effectively increases the ratio of KCC2/NKCC1, restores RDD levels, enhances GABAA receptor-mediated inhibitory function in the spinal cord, and relieves neuropathic pain in SCI; Bumetanide significantly improves neuropathic pain in the long term, whereas CLP290 demonstrates a notable short-term effect.

The role of foam cells in spinal cord injury: challenges and opportunities for intervention.

Spinal cord injury (SCI) results in a large amount of tissue cell debris in the lesion site, which interacts with various cytokines, including inflammatory factors, and the intrinsic glial environment of the central nervous system (CNS) to form an inhibitory microenvironment that impedes nerve regeneration. The efficient clearance of tissue debris is crucial for the resolution of the inhibitory microenvironment after SCI. Macrophages are the main cells responsible for tissue debris removal after SCI. However, the high lipid content in tissue debris and the dysregulation of lipid metabolism within macrophages lead to their transformation into foamy macrophages during the phagocytic process. This phenotypic shift is associated with a further pro-inflammatory polarization that may aggravate neurological deterioration and hamper nerve repair. In this review, we summarize the phenotype and metabolism of macrophages under inflammatory conditions, as well as the mechanisms and consequences of foam cell formation after SCI. Moreover, we discuss two strategies for foam cell modulation and several potential therapeutic targets that may enhance the treatment of SCI.

Glycine and N-Acetylcysteine (GlyNAC) Combined with Body Weight Support Treadmill Training Improved Spinal Cord and Skeletal Muscle Structure and Function in Rats with Spinal Cord Injury.

Skeletal muscle atrophy is a frequent complication after spinal cord injury (SCI) and can influence the recovery of motor function and metabolism in affected patients. Delaying skeletal muscle atrophy can promote functional recovery in SCI rats. In the present study, we investigated whether a combination of body weight support treadmill training (BWSTT) and glycine and N-acetylcysteine (GlyNAC) could exert neuroprotective effects, promote motor function recovery, and delay skeletal muscle atrophy in rats with SCI, and we assessed the therapeutic effects of the double intervention from both a structural and functional viewpoint. We found that, after SCI, rats given GlyNAC alone showed an improvement in Basso-Beattie-Bresnahan (BBB) scores, gait symmetry, and results in the open field test, indicative of improved motor function, while GlyNAC combined with BWSTT was more effective than either treatment alone at ameliorating voluntary motor function in injured rats. Meanwhile, the results of the skeletal muscle myofiber cross-sectional area (CSA), hindlimb grip strength, and acetylcholinesterase (AChE) immunostaining analysis demonstrated that GlyNAC improved the structure and function of the skeletal muscle in rats with SCI and delayed the atrophication of skeletal muscle.

The Effect of Glycine and N-Acetylcysteine on Oxidative Stress in the Spinal Cord and Skeletal Muscle After Spinal Cord Injury.

Oxidative stress is a frequently occurring pathophysiological feature of spinal cord injury (SCI) and can result in secondary injury to the spinal cord and skeletal muscle atrophy. Studies have reported that glycine and N-acetylcysteine (GlyNAC) have anti-aging and anti-oxidative stress properties; however, to date, no study has assessed the effect of GlyNAC in the treatment of SCI. In the present work, we established a rat model of SCI and then administered GlyNAC to the animals by gavage at a dose of 200 mg/kg for four consecutive weeks. The BBB scores of the rats were significantly elevated from the first to the eighth week after GlyNAC intervention, suggesting that GlyNAC promoted the recovery of motor function; it also promoted the significant recovery of body weight of the rats. Meanwhile, the 4-week heat pain results also suggested that GlyNAC intervention could promote the recovery of sensory function in rats to some extent. Additionally, after 4 weeks, the levels of glutathione and superoxide dismutase in spinal cord tissues were significantly elevated, whereas that of malondialdehyde was significantly decreased in GlyNAC-treated animals. The gastrocnemius wet weight ratio and total antioxidant capacity were also significantly increased. After 8 weeks, the malondialdehyde level had decreased significantly in spinal cord tissue, while reactive oxygen species accumulation in skeletal muscle had decreased. These findings suggested that GlyNAC can protect spinal cord tissue, delay skeletal muscle atrophy, and promote functional recovery in rats after SCI.

Mechanism of skeletal muscle atrophy after spinal cord injury: A narrative review.

Spinal cord injury leads to loss of innervation of skeletal muscle, decreased motor function, and significantly reduced load on skeletal muscle, resulting in atrophy. Factors such as braking, hormone level fluctuation, inflammation, and oxidative stress damage accelerate skeletal muscle atrophy. The atrophy process can result in skeletal muscle cell apoptosis, protein degradation, fat deposition, and other pathophysiological changes. Skeletal muscle atrophy not only hinders the recovery of motor function but is also closely related to many systemic dysfunctions, affecting the prognosis of patients with spinal cord injury. Extensive research on the mechanism of skeletal muscle atrophy and intervention at the molecular level has shown that inflammation and oxidative stress injury are the main mechanisms of skeletal muscle atrophy after spinal cord injury and that multiple pathways are involved. These may become targets of future clinical intervention. However, most of the experimental studies are still at the basic research stage and still have some limitations in clinical application, and most of the clinical treatments are focused on rehabilitation training, so how to develop more efficient interventions in clinical treatment still needs to be further explored. Therefore, this review focuses mainly on the mechanisms of skeletal muscle atrophy after spinal cord injury and summarizes the cytokines and signaling pathways associated with skeletal muscle atrophy in recent studies, hoping to provide new therapeutic ideas for future clinical work.

Diffusion tensor imaging reveals brain structure changes in dogs after spinal cord injury.

Based on the Wallerian degeneration in the spinal cord pathways, the changes in synaptic connections, and the spinal cord-related cellular responses that alter the cellular structure of the brain, we presumed that brain diffusion tensor imaging (DTI) parameters may change after spinal cord injury. However, the dynamic changes in DTI parameters remain unclear. We established a Beagle dog model of T10 spinal cord contusion and performed DTI of the injured spinal cord. We found dynamic changes in DTI parameters in the cerebral peduncle, posterior limb of the internal capsule, pre- and postcentral gyri of the brain within 12 weeks after spinal cord injury. We then performed immunohistochemistry to detect the expression of neurofilament heavy polypeptide (axonal marker), glial fibrillary acidic protein (glial cell marker), and NeuN (neuronal marker). We found that these pathological changes were consistent with DTI parameter changes. These findings suggest that DTI can display brain structure changes after spinal cord injury.

The Effect of Vocal Intonation Therapy on Vocal Dysfunction in Patients With Cervical Spinal Cord Injury: A Randomized Control Trial.

In this study, the vocal intonation therapy (VIT) was compared with the standard respiratory therapy for people suffering from respiratory dysfunction as a result of cervical spinal cord injury (CSCI) to observe its effect on vocal quality. Thirty patients with vocal dysfunction after CSCI with the injury time of more than 3 months were screened for inclusion in the trial, and 18 patients completed the 12-weeks, each participant had 60 sessions in total in the clinical trial. All patients were allocated to the intervention group or the control group. The intervention group received VIT training and the control group received respiratory phonation therapy. Both groups were trained by professional therapists, and the training time was 30 min/day, 5 days/week, for 60 sessions for each group in a total of 12 weeks. In the Baseline (T0), mid-intervention period (after 6 weeks, T1), and after intervention (after 12 weeks, T2), the vocal quality of the two groups of patients was tested with a computer-aided real-time audio analyzer 2.1.6 (Adobe Systems, United States) for Sing-SPL (p < 0.0001), Speech-SPL (p < 0.0001), SNL (p < 0.0001), and F0 (p < 0.0001) of the intervention group were significantly improved compared with the control group. In comparing the spectrometry analysis of vocal quality for the 2 groups of participants, there was a significant difference in the results of Sing-SPL and Speech-SPL acoustic analysis in the intervention group of patients at T2 (after 12 weeks) compared to the control group. Vocal intonation therapy-music therapy can improve the speech sound quality of cervical CSCI patients and provide CSCI patients with a practical, highly operable treatment that has both functional training effects and can bring a pleasant experience that can be promoted in the medical field. This study was approved by the Ethics Committee of China Rehabilitation Research Center (CRRC) (approval No. 2019-83-1) on May 20th, 2019. It was registered with the National Health Security Information Platform, medical research registration, and filing information system (Registration No. MR-11-21-011802) on January 28th, 2021.

Sodium selenite promotes neurological function recovery after spinal cord injury by inhibiting ferroptosis.

Ferroptosis is a recently discovered form of iron-dependent cell death, which occurs during the pathological process of various central nervous system diseases or injuries, including secondary spinal cord injury. Selenium has been shown to promote neurological function recovery after cerebral hemorrhage by inhibiting ferroptosis. However, whether selenium can promote neurological function recovery after spinal cord injury as well as the underlying mechanism remain poorly understood. In this study, we injected sodium selenite (3 µL, 2.5 µM) into the injury site of a rat model of T10 vertebral contusion injury 10 minutes after spinal cord injury modeling. We found that sodium selenite treatment greatly decreased iron concentration and levels of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal. Furthermore, sodium selenite increased the protein and mRNA expression of specificity protein 1 and glutathione peroxidase 4, promoted the survival of neurons and oligodendrocytes, inhibited the proliferation of astrocytes, and promoted the recovery of locomotive function of rats with spinal cord injury. These findings suggest that sodium selenite can improve the locomotive function of rats with spinal cord injury possibly through the inhibition of ferroptosis via the specificity protein 1/glutathione peroxidase 4 pathway.

Effect of vocal respiratory training on respiratory function and respiratory neural plasticity in patients with cervical spinal cord injury: a randomized controlled trial.

In previous studies, researchers have used singing to treat respiratory function in patients with spinal cord injury. However, few studies have examined the way in which vocal training affects respiratory neural plasticity in patients with spinal cord injury. Vocal respiratory training (VRT) is a type of vocal muscle-related treatment that is often a component of music therapy (MT) and focuses on strengthening respiratory muscles and improving lung function. In this randomized controlled study, we analyzed the therapeutic effects of VRT on respiratory dysfunction at 3 months after cervical spinal cord injury. Of an initial group of 37 patients, 26 completed the music therapy intervention, which comprised five 30-minute sessions per week for 12 weeks. The intervention group (n = 13) received VRT training delivered by professional certified music therapists. The control group (n = 13) received respiratory physical therapy delivered by professional physical therapists. Compared with the control group, we observed a substantial increase in respiratory function in the intervention group after the 12-week intervention. Further, the nerve fiber bundles in the respiratory center in the medulla exhibited a trend towards increased diversification, with an increased number, path length, thickness, and density of nerve fiber bundles. These findings provide strong evidence for the effect of music therapeutic VRT on neural plasticity. This study was approved by the Ethics Committee of China Rehabilitation Research Center (approval No. 2020-013-1) on April 1, 2020, and was registered with the Chinese Clinical Trial Registry (registration No. ChiCTR2000037871) on September 2, 2020.

Elevated plasma histone H4 level predicts increased risk of mortality in patients with sepsis.

BACKGROUND: Histones play a vital role in the pathogenesis of sepsis. However, studies on histones and the prognosis of sepsis patients are scarce. This study aims to investigate the relationship between histones and other biomarkers of sepsis. Furthermore, we aim to determine the role histones play in the prognosis of sepsis patients to explore the possibility of using them as a potential biomarker of sepsis. METHODS: We performed a prospective observational study on 136 patients. One hundred twenty-six of them had sepsis, and 10 were enrolled as healthy controls. Baseline blood samples were collected for plasma histone H4, cardiac troponin I (TnI), N-terminal pro-b-type natriuretic peptide (NT-proBNP), procalcitonin (PCT), and lactate. The site of infection, the use of vasopressor, and assessment scores of sequential organ failure were documented within 24 hours of admission. The duration of ICU stay and mortality was also recorded. RESULTS: The mean plasma histone levels of the patients were significantly higher than the healthy controls (P<0.001). Compared with the 89 survivors, the 37 patients who died had a higher rate of sequential organ failure assessment (SOFA) scores (P=0.002), more frequent use of vasopressors (P=0.033), and higher levels of histone H4 (P<0.001). Binary logistic regression analysis showed that high plasma histone H4 levels were independent risk factors for predicting mortality. The area under the receiver operating characteristic curve (0.731) verified that high plasma histone H4 level significantly predicted mortality. Plasma histone H4 levels positively correlated with the SOFA score, and plasma cardiac TnI. CONCLUSIONS: For patients with sepsis in the ICU, an elevated level of plasma histone H4 could be a risk factor associated with an increased mortality rate. Therefore, plasma histone H4 may be a useful biomarker for determining the prognosis of these patients.

Is the efficacy of repetitive transcranial magnetic stimulation influenced by baseline severity of fatigue symptom in patients with myalgic encephalomyelitis.

Objectives: Recently, repetitive transcranial magnetic stimulation (rTMS) has been therapeutically applied for patients with myalgic encephalomyelitis (ME). However, it is still unclear which clinical factors could influence the efficacy of rTMS for ME patients. The purpose of this study is to clarify whether baseline severity of fatigue symptom would influence the efficacy of rTMS applied for ME patients.Methods: Twenty-two patients with ME were studied. Each patient was hospitalized to receive 6-8 sessions of rTMS. In this study, high-frequency rTMS of 10 Hz was applied over prefrontal cortex. To evaluate the severity of fatigue symptom, Brief Fatigue Inventory (BFI) score and Visual Analogue Scale (VAS) rate were applied before and after rTMS application. Based on the BFI score before rTMS, the patients were divided into two groups: 'severe group' (n = 9) and 'mild group' (n = 13). We compared the extent of the improvements of fatigue symptom between two groups.Results: In severe group, compared to before rTMS, VAS rate was significantly lower not only at discharge but also 2 weeks after discharge. Similarly, mild group also showed significant decrease in VAS rate at the same timepoints. However, the extent of VAS rate change did not differ between two groups. In addition, no significant correlation between baseline score of BFI and the changes in VAS rate was indicated.Conclusions: It can be concluded that rTMS can improve fatigue symptom in ME patients regardless of baseline severity of fatigue symptom. It is expected that rTMS can be a novel therapeutic intervention for ME patients.

The Ability for Basic Movement Scale II Can Predict Functional Outcome and Discharge Destination in Stroke Patients.

OBJECTIVES: This study aims to identify whether the Ability for Basic Movement Scale II (ABMS II) at admission would predict the functional status and discharge destination in convalescent stroke patients. METHODS: Ninety-four stroke patients admitted to convalescent rehabilitation ward were investigated. Their functions were evaluated by the ABMS II and Functional Independence Measure (FIM) at admission, FIM and Functional Ambulation Category at discharge. Furthermore, the age, gender, diagnosis, lesion side, onset type, interval between onset and convalescent admission, length of stay (LOS) and discharge destination were recorded. Discharge destination was divided into home and facility. RESULTS: Multiple linear regression identified the ABMS II at admission as a significant predicator of discharge FIM in convalescent stroke patients (ß = .747, P < .05). Binary logistic regression analysis showed the ABMS II significantly predicting basic walk ability (odds ratio 1.29) and home discharge (odds ratio 1.241) of these patients. Receiver operating characteristic analysis indicated that an optimal cutoff of 18 points of ABMS II predicted basic walk ability (area under the curve = .863, P < .05) and home discharge (area under the curve = .827, P < .05). Moreover, a significant negative correlation between the ABSM II at admission and LOS was found (Correlation coefficients -.680, P < .05). CONCLUSIONS: Higher score of the ABMS II at admission predicted better functional recovery, shorter LOS and more possibility to home in convalescent stroke patients. This new, easy scale is expected to be widely used for stroke patients.

Elevated Plasma Histone H4 Levels Are an Important Risk Factor in the Development of Septic Cardiomyopathy

Background: Myocardial impairment is a major complication and an important prognostic predictor of sepsis. Therefore, early and accurate diagnosis as well as timely management of septic cardiomyopathy is critical to achieve favorable outcomes. Aims: To investigate the risk factors of septic cardiomyopathy. Study Design: Cross-sectional study. Methods: This study performed between May 2016 and June 2018 recruited 93 septic patients from the intensive care unit. All patients received standardized treatments. Septic patients were divided into two groups: non cardiomyopathy (n=45) and septic cardiomyopathy group (n=48). Blood samples were collected and transthoracic echocardiography was performed within 24 hours of intensive care unit admission. Septic patients with one ultrasound abnormality but no history of heart disease were diagnosed as having septic cardiomyopathy. Plasma histones, cardiac troponin I, and N-terminal pro-brain natriuretic peptide were measured using ELISA. Sequential Organ Failure Assessment scores, vasopressor use, and the outcomes of intensive care unit stay were analyzed. Spearman rank analysis was used to determine the correlation between plasma histone H4 and other parameters. Binary logistic regression and receiver operating characteristic curve analysis were used to determine the risk factors for septic cardiomyopathy. Results: Compared with the non-cardiomyopathy group, the septic cardiomyopathy group had significantly higher plasma H4 and cardiac troponin I levels, a higher Sequential Organ Failure Assessment score, more frequent vasopressor use, and a higher mortality rate (p<0.05). Plasma histone H4 levels positively correlated with cardiac troponin I (r=0.577, p<0.001), N-terminal pro-brain natriuretic peptide (r=0.349, p=0.001), and Sequential Organ Failure Assessment scores (r=0.469, p<0.001). Binary logistic regression and receiver operating characteristic curve analyses revealed that elevated plasma histone H4 levels and vasopressor use were important risk factors for septic cardiomyopathy (p<0.05). Conclusion: Elevated plasma histone H4 levels could be used to predict septic cardiomyopathy in patients with sepsis.

Pathological significance of tRNA-derived small RNAs in neurological disorders.

Non-coding RNAs (ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs (tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cleaved into a heterogeneous population of ncRNAs with lengths of 18-40 nucleotides, known as tRNA-derived small RNAs (tsRNAs). There are two main types of tsRNA, based on their length and the number of cleavage sites that they contain: tRNA-derived fragments and tRNA-derived stress-induced RNAs. These RNA species were first considered to be byproducts of tRNA random cleavage. However, mounting evidence has demonstrated their critical functional roles as regulatory factors in the pathophysiological processes of various diseases, including neurological diseases. However, the underlying mechanisms by which tsRNAs affect specific cellular processes are largely unknown. Therefore, this study comprehensively summarizes the following points: (1) The biogenetics of tsRNA, including their discovery, classification, formation, and the roles of key enzymes. (2) The main biological functions of tsRNA, including its miRNA-like roles in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress. (3) The potential mechanisms of pathophysiological changes in neurological diseases that are regulated by tsRNA, including neurodegeneration and neurotrauma. (4) The identification of the functional diversity of tsRNA may provide valuable information regarding the physiological and pathophysiological mechanisms of neurological disorders, thus providing a new reference for the clinical treatment of neurological diseases. Research into tsRNAs in neurological diseases also has the following challenges: potential function and mechanism studies, how to accurately quantify expression, and the exact relationship between tsRNA and miRNA. These challenges require future research efforts.

Dynamic changes in intramedullary pressure 72 hours after spinal cord injury.

Intramedullary pressure increases after spinal cord injury, and this can be an important factor for secondary spinal cord injury. Until now there have been no studies of the dynamic changes of intramedullary pressure after spinal cord injury. In this study, telemetry systems were used to observe changes in intramedullary pressure in the 72 hours following spinal cord injury to explore its pathological mechanisms. Spinal cord injury was induced using an aneurysm clip at T10 of the spinal cord of 30 Japanese white rabbits, while another 32 animals were only subjected to laminectomy. The feasibility of this measurement was assessed. Intramedullary pressure was monitored in anesthetized and conscious animals. The dynamic changes of intramedullary pressure after spinal cord injury were divided into three stages: stage I (steep rise) 1-7 hours, stage II (steady rise) 8-38 hours, and stage III (descending) 39-72 hours. Blood-spinal barrier permeability, edema, hemorrhage, and histological results in the 72 hours following spinal cord injury were evaluated according to intramedullary pressure changes. We found that spinal cord hemorrhage was most severe at 1 hour post-spinal cord injury and then gradually decreased; albumin and aquaporin 4 immunoreactivities first increased and then decreased, peaking at 38 hours. These results confirm that severe bleeding in spinal cord tissue is the main cause of the sharp increase in intramedullary pressure in early spinal cord injury. Spinal cord edema and blood-spinal barrier destruction are important factors influencing intramedullary pressure in stages II and III of spinal cord injury.

Degeneration of white matter and gray matter revealed by diffusion tensor imaging and pathological mechanism after spinal cord injury in canine.

AIM: Exploration of the mechanism of spinal cord degeneration may be the key to treatment of spinal cord injury (SCI). This study aimed to investigate the degeneration of white matter and gray matter and pathological mechanism in canine after SCI. METHODS: Diffusion tensor imaging (DTI) was performed on canine models with normal (n = 5) and injured (n = 7) spinal cords using a 3.0T MRI scanner at precontusion and 3 hours, 24 hours, 6 weeks, and 12 weeks postcontusion. The tissue sections were stained using H&E and immunohistochemistry. RESULTS: For white matter, fractional anisotropy (FA) values significantly decreased in lesion epicenter, caudal segment 1 cm away from epicenter, and caudal segment 2 cm away from epicenter (P = 0.003, P = 0.004, and P = 0.013, respectively) after SCI. Apparent diffusion coefficient (ADC) values were initially decreased and then increased in lesion epicenter and caudal segment 1 cm away from epicenter (P < 0.001 and P = 0.010, respectively). There are no significant changes in FA and ADC values in rostral segments (P > 0.05). For gray matter, ADC values decreased initially and then increased in lesion epicenter (P < 0.001), and overall trend decreased in caudal segment 1 cm away from epicenter (P = 0.039). FA values did not change significantly (P > 0.05). Pathological examination confirmed the dynamic changes of DTI parameters. CONCLUSION: Diffusion tensor imaging is more sensitive to degeneration of white matter than gray matter, and the white matter degeneration may be not symmetrical which meant the caudal degradation appeared to be more severe than the rostral one.

Differential Expression Profiles and Functional Prediction of tRNA-Derived Small RNAs in Rats After Traumatic Spinal Cord Injury.

Spinal cord injury (SCI) is mostly caused by trauma. As the primary mechanical injury is unavoidable, a focus on the underlying molecular mechanisms of the SCI-induced secondary injury is necessary to develop promising treatments for patients with SCI. Transfer RNA-derived small RNA (tsRNA) is a novel class of short, non-coding RNA, possessing potential regulatory functions in various diseases. However, the functional roles of tsRNAs in traumatic SCI have not been determined yet. We used a combination of sequencing, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), bioinformatics, and luciferase reporter assay to screen the expression profiles and identify the functional roles of tsRNAs after SCI. As a result, 297 differentially expressed tsRNAs were identified in rats' spinal cord 1 day after contusion. Of those, 155 tsRNAs were significantly differentially expressed: 91 were significantly up-regulated, whereas 64 were significantly down-regulated after SCI (fold change > 1.5; P < 0.05). Bioinformatics analyses revealed candidate tsRNAs (tiRNA-Gly-GCC-001, tRF-Gly-GCC-012, tRF-Gly-GCC-013, and tRF-Gly-GCC-016) that might play regulatory roles through the mitogen-activated protein kinase (MAPK) and neurotrophin signaling pathways by targeting brain-derived neurotrophic factor (BDNF). We validated the candidate tsRNAs and found opposite trends in the expression levels of the tsRNAs and BDNF after SCI. Finally, tiRNA-Gly-GCC-001 was identified to target BDNF using the luciferase reporter assay. In summary, we found an altered tsRNA expression pattern and predicted tiRNA-Gly-GCC-001 might be involved in the MAPK and neurotrophin pathways by targeting the BDNF, thus regulating the post-SCI pathophysiologic processes. This study provides novel insights for future investigations to explore the mechanisms and therapeutic targets for SCI.

Induced Pluripotent Stem Cell Transplantation Improves Locomotor Recovery in Rat Models of Spinal Cord Injury: a Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND/AIMS: Spinal cord injury (SCI) has long been a subject of great interest in a wide range of scientific fields. Several attempts have been made to demonstrate motor function improvement in rats with SCI after transplantation of induced pluripotent stem cells (iPSC). This systematic review and meta-analysis was designed to summarize the effects of iPSC on locomotor recovery in rat models of SCI. METHODS: We searched the publications in the PubMed, Medline, Science Citation Index, Cochrane Library, CNKI, and Wan-fang databases and the China Biology Medicine disc. Results were analyzed by Review Manager 5.3.0. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: Six randomized controlled preclinical trials covering eight comparisons and including 212 rats were selected. The subgroup analyses were based on the following items: different SCI models, cell counts, iPSC sources, iPSC differentiations and transplantation methods. The pooled results indicated that iPSC transplantation significantly improved locomotor recovery of rats after SCI by sustaining beneficial effects, especially in the subgroups of contusion, moderate cell counts (5×105), source of human fetal lung fibroblasts, iPSC-neural precursors and intraspinal injection. CONCLUSION: Our meta-analysis of the effects of iPSC transplantation on locomotor function in SCI models is, to our knowledge, the first meta-analysis in this field. We conclude that iPSC transplantation improves locomotor recovery in rats with SCI, implicating this strategy as an effective therapy. However, more studies are required to validate our conclusions.

A rare case of type 1 leprosy reactions following tetanus infection in a borderline tuberculoid leprosy patient and a literature review.

BACKGROUND: Type 1 leprosy reaction, also known as "reversal reaction", is related to cellular immune responses to Mycobacterium leprae antigens. The risk factors that trigger type 1 leprosy reactions are poorly understood. Leprosy with concurrent tetanus is rare, and there are no publicly available reports of a leprosy patient infected with tetanus that induced type 1 leprosy reactions. CASE PRESENTATION: A 56-year-old Chinese Han female presented to our hospital with symptoms of erythematous plaques and pain over her left upper limb for 2 days and foreign object sensation in her throat for 3 days. The patient had a 6-year history of leprosy. Type 1 leprosy reactions were initially considered, followed by treatment with methylprednisolone. Two days later, the patient's symptoms were aggravated, with neck muscle tension and difficulty in opening her mouth, and the erythematous plaques had spread over most of her left upper limb. After further careful examinations, we confirmed the diagnosis of tetanus with concurrent type 1 leprosy reactions. The patient was given anti-tetanus treatment for 12 days and anti-leprosy reaction treatment for 4 months; the diseases were eventually controlled. CONCLUSIONS: This report suggests that tetanus infection may be a trigger for type 1 leprosy reactions.

Dynamic correlation of diffusion tensor imaging and neurological function scores in beagles with spinal cord injury.

Exploring the relationship between different structure of the spinal cord and functional assessment after spinal cord injury is important. Quantitative diffusion tensor imaging can provide information about the microstructure of nerve tissue and can quantify the pathological damage of spinal cord white matter and gray matter. In this study, a custom-designed spinal cord contusion-impactor was used to damage the T10 spinal cord of beagles. Diffusion tensor imaging was used to observe changes in the whole spinal cord, white matter, and gray matter, and the Texas Spinal Cord Injury Score was used to assess changes in neurological function at 3 hours, 24 hours, 6 weeks, and 12 weeks after injury. With time, fractional anisotropy values after spinal cord injury showed a downward trend, and the apparent diffusion coefficient, mean diffusivity, and radial diffusivity first decreased and then increased. The apparent diffusion-coefficient value was highly associated with the Texas Spinal Cord Injury Score for the whole spinal cord (R = 0.919, P = 0.027), white matter (R = 0.932, P = 0.021), and gray matter (R = 0.882, P = 0.048). Additionally, the other parameters had almost no correlation with the score (P > 0.05). In conclusion, the highest and most significant correlation between diffusion parameters and neurological function was the apparent diffusion-coefficient value for white matter, indicating that it could be used to predict the recovery of neurological function accurately after spinal cord injury.