Spinal cord injury-induced gut dysbiosis influences neurological recovery partly through short-chain fatty acids.

Spinal cord injury (SCI) can reshape gut microbial composition, significantly affecting clinical outcomes in SCI patients. However, mechanisms regarding gut-brain interactions and their clinical implications have not been elucidated. We hypothesized that short-chain fatty acids (SCFAs), intestinal microbial bioactive metabolites, may significantly affect the gut-brain axis and enhance functional recovery in a mouse model of SCI. We enrolled 59 SCI patients and 27 healthy control subjects and collected samples. Thereafter, gut microbiota and SCFAs were analyzed using 16 S rDNA sequencing and gas chromatography-mass spectrometry, respectively. We observed an increase in Actinobacteriota abundance and a decrease in Firmicutes abundance. Particularly, the SCFA-producing genera, such as Faecalibacterium, Megamonas, and Agathobacter were significantly downregulated among SCI patients compared to healthy controls. Moreover, SCI induced downregulation of acetic acid (AA), propionic acid (PA), and butyric acid (BA) in the SCI group. Fecal SCFA contents were altered in SCI patients with different injury course and injury segments. Main SCFAs (AA, BA, and PA) were administered in combination to treat SCI mice. SCFA supplementation significantly improved locomotor recovery in SCI mice, enhanced neuronal survival, promoted axonal formation, reduced astrogliosis, and suppressed microglial activation. Furthermore, SCFA supplementation downregulated NF-κB signaling while upregulating neurotrophin-3 expression following SCI. Microbial sequencing and metabolomics analysis showed that SCI patients exhibited a lower level of certain SCFAs and related bacterial strains than healthy controls. SCFA supplementation can reduce inflammation and enhance nourishing elements, facilitating the restoration of neurological tissues and the improvement of functional recuperation. Trial registration: This study was registered in the China Clinical Trial Registry ( www.chictr.org.cn ) on February 13, 2017 (ChiCTR-RPC-17010621).

Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion Site.

The primary traumatic event that causes spinal cord injury (SCI) is followed by a progressive secondary injury featured by vascular disruption and ischemia, inflammatory responses and the release of cytotoxic debris, which collectively add to the hostile microenvironment of the lesioned cord and inhibit tissue regeneration and functional recovery. In a previous study, we reported that fecal microbiota transplantation (FMT) promotes functional recovery in a contusion SCI mouse model; yet whether and how FMT treatment may impact the microenvironment at the injury site are not well known. In the current study, we examined individual niche components and investigated the effects of FMT on microcirculation, inflammation and trophic factor secretion in the spinal cord of SCI mice. FMT treatment significantly improved spinal cord tissue sparing, vascular perfusion and pericyte coverage and blood-spinal cord-barrier (BSCB) integrity, suppressed the activation of microglia and astrocytes, and enhanced the secretion of neurotrophic factors. Suppression of inflammation and upregulation of trophic factors, jointly, may rebalance the niche homeostasis at the injury site and render it favorable for reparative and regenerative processes, eventually leading to functional recovery. Furthermore, microbiota metabolic profiling revealed that amino acids including ß-alanine constituted a major part of the differentially detected metabolites between the groups. Supplementation of ß-alanine in SCI mice reduced BSCB permeability and increased the number of surviving neurons, suggesting that ß-alanine may be one of the mediators of FMT that participates in the modulation and rebalancing of the microenvironment at the injured spinal cord. IMPORTANCE FMT treatment shows a profound impact on the microenvironment that involves microcirculation, blood-spinal cord-barrier, activation of immune cells, and secretion of neurotrophic factors. Analysis of metabolic profiles reveals around 22 differentially detected metabolites between the groups, and ß-alanine was further chosen for functional validation experiments. Supplementation of SCI mice with ß-alanine significantly improves neuronal survival, and the integrity of blood-spinal cord-barrier at the lesion site, suggesting that ß-alanine might be one of the mediators following FMT that has contributed to the recovery.

Lower-Limb Sensorimotor Deprivation-Related Brain Activation in Patients With Chronic Complete Spinal Cord Injury.

This study aims to investigate functional brain reorganization brought about by the loss of physical movement and sensory feedback in lower limbs in chronic spinal cord injury (SCI). Eleven paraplegia patients with SCI and 13 healthy controls (HCs) were recruited. The experimental task used was a visuomotor imagery task requiring subjects to engage in visualization of repetitive tapping movements of the upper or lower limbs. Blood oxygen level-dependent (BOLD) responses were captured during the experimental task, along with the accuracy rate and the response time. The SCI patients performed worse in the Rey Auditory Verbal Learning Test (RAVLT) and the Trail Making Test. SCI patients had a larger BOLD signal in the left lingual gyrus and right external globus pallidus (GPe) when imagining lower-limb movements. For the upper-limb task, SCI patients showed stronger BOLD responses than the HCs in extensive areas over the brain, including the bilateral precentral gyrus (preCG), bilateral inferior parietal gyrus, right GPe, right thalamus, left postcentral gyrus, and right superior temporal gyrus. In contrast, the HCs displayed stronger BOLD responses in the medial frontal gyrus and anterior cingulate gyrus for both upper- and lower-limb tasks than the SCI patients. In the SCI group, for the upper-limb condition, the amplitudes of BOLD responses in the left preCG were negatively correlated with the time since injury (r = -0.72, p = 0.012). For the lower-limb condition, the amplitudes of BOLD responses in the left lingual gyrus were negatively correlated with the scores on the Short Delay task of the RAVLT (r = -0.73, p = 0.011). Our study provided imaging evidence for abnormal changes in brain function and worsened cognitive test performance in SCI patients. These findings suggested possible compensatory strategies adopted by the SCI patients for the loss of sensorimotor function from the lower limbs when performing a limb imagery task.

Photothermal therapy enhanced the effectiveness of imiquimod against refractory cutaneous warts through boosting immune responses.

Refractory cutaneous warts are difficult to eliminate. In situ photo-immunotherapy (ISPI) is an innovative treatment concept combining local photothermal therapy (PTT) and topical immunotherapy using imiquimod. To compare the efficacy of ISPI vs topical imiquimod alone, a prospective randomized controlled trial was performed with patients suffering from refractory cutaneous warts. In both groups, approximately 50% of the skin surface containing warts was treated for 6 weeks. On the basis of topical imiquimod, ISPI includes an additional 808 nm laser irradiation. Treatment response, temperatures during irradiation and histopathologic examination were evaluated. The complete response rate in the ISPI-group (22/36, 61.1%) was significantly higher than in the imiquimod alone group (11/34, 32.4%). In the ISPI-group, the mean maximum temperature was 44.5 ± 5.1°C, and obvious lymphocytic infiltration was found in the perivasculature of the dermis. There was no recurrence or worsening in both groups during the 12-month follow-up. No obvious adverse reaction was observed. This study demonstrates that ISPI can be used as an effective and safe treatment modality for refractory cutaneous warts.

Laser immunotherapy for cutaneous squamous cell carcinoma with optimal thermal effects to enhance tumour immunogenicity.

BACKGROUND: Laser immunotherapy is a new anti-cancer therapy combining photothermal therapy and immunostimulation. It can eliminate the tumours by damaging tumour cells directly and promoting the release of damage-associated molecular patterns (DAMPs) to enhance tumour immunogenicity. The aim of this study was to investigate the thermal effects of laser immunotherapy and to evaluate the effectiveness and safety of laser immunotherapy for cutaneous squamous cell carcinoma (cSCC). METHODS: The cell viability and the DAMPs productions of heat-treated cSCC A431 cells in different temperatures were investigated. Laser immunotherapy with the optimal thermal effect for DAMPs production was performed on SKH-1 mice bearing ultraviolet-induced cSCC and a patient suffering from a large refractory cSCC. RESULTS: The temperature in the range of 45-50 °C killing half of A431 cells had an optimal thermal effect for the productions of DAMPs. The thermal effect could be further enhanced by local application of imiquimod, an immunoadjuvant. Laser immunotherapy eliminated most tumours and improved the survival rate of the ultraviolet-induced cSCC-bearing SKH-1 mice (p < 0.05). The patient with cSCC treated by laser immunotherapy experienced a significant tumour reduction after laser immunotherapy increased the amounts of infiltrating lymphocytes in the tumour. No obviously adverse effect was observed in the mice experiment or in the clinical application. CONCLUSIONS: Our results strongly indicate that laser immunotherapy with optimal thermal effects is an effective and safe treatment modality for cSCC.

The immediate effects of therapeutic keyboard music playing for finger training in adults undergoing hand rehabilitation.

[Purpose] The purpose of this study was to examine the immediate effects of therapeutic keyboard music playing on the finger function of subjects' hands through measurements of the joint position error test, surface electromyography, probe reaction time, and writing time. [Subjects and Methods] Ten subjects were divided randomly into experimental and control groups. The experimental group used therapeutic keyboard music playing and the control group used grip training. All subjects were assessed and evaluated by the joint position error test, surface electromyography, probe reaction time, and writing time. [Results] After accomplishing therapeutic keyboard music playing and grip training, surface electromyography of the two groups showed no significant change, but joint position error test, probe reaction time, and writing time obviously improved. [Conclusion] These results suggest that therapeutic keyboard music playing is an effective and novel treatment for improving joint position error test scores, probe reaction time, and writing time, and it should be promoted widely in clinics.

[Changes of plasma fibrinogen level among acute ischemic stroke subtypes according to TOAST criteria and effects of Songling Xuemaikang].

OBJECTIVE: To investigate the changes of plasma fibrinogen level among acute ischemic stroke (ACI) subtypes according to Trial of Org10172 in Acute Stroke Treatment (TOAST) criteria and effects of Songling Xuemaikang. METHOD: The 160 patients with acute ischemic stroke were divided into two groups randomly: treatment group 85 cases (Songling Xuemaikang + Shuxuetong + Aspirin enterie coated tablets), control group 75 cases (Shuxuetong + Aspirin enterie ccoated tablets). The plasma fibrinogen was detected before and after treatment. RESULT: Compared with OC subtype, Fbg was higher in LAA, CE and SAO subtypes (P < 0.05). Compared with UE subtype, Fbg was higher in LAA, CE and SAO subtypes (P < 0.05). There was a significantly difference between LAA and SAO (P < 0.05). In LAA, SAO, CE of treatment group,the Fbg level were lowered significantly at the 15th day compared with pretherapy (P < 0.05). There was a significantly difference of Fbg between treatment group and control group In LAA, SAO and CE subtypes at the 15th day (P < 0.05). CONCLUSION: Fbg produces a marked effect at the pathomechanism of LAA, SAO and CE subtypes. Songling Xuemaikang can depress the plasma fibrinogen level of ACI, and be an effective adjunctive therapy on ACI.