A nomogram for predicting residual low back pain after percutaneous kyphoplasty in osteoporotic vertebral compression fractures.

To establish a risk prediction model for residual low back pain after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures. We used retrospective data for model construction and evaluated the model using internal validation and temporal external validation and finally concluded that the model had good predictive performance. INTRODUCTION: The cause of residual low back pain in patients with osteoporotic vertebral compression fractures (OVCFs) after PKP remains highly controversial, and our goal was to investigate the most likely cause and to develop a novel nomogram for the prediction of residual low back pain and to evaluate the predictive performance of the model. METHODS: The clinical data of 281 patients with OVCFs who underwent PKP at our hospital from July 2019 to July 2020 were reviewed. The optimal logistic regression model was determined by lasso regression for multivariate analysis, thus constructing a nomogram. Bootstrap was used to perfomance the internal validation; receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to assess the predictive performance and clinical utility of the model, respectively. Temporal external validation of the model was also performed using retrospective data from 126 patients who underwent PKP at our hospital from January 2021 to October 2021. RESULTS: Lasso regression cross-validation showed that the variables with non-zero coefficients were the number of surgical vertebrae, preoperative bone mineral density (pre-BMD), smoking history, thoracolumbar fascia injury (TLFI), intraoperative facet joint injury (FJI), and postoperative incomplete cementing of the fracture line (ICFL). The above factors were included in the multivariate analysis and showed that the pre-BMD, smoking history, TLFI, FJI, and ICFL were independent risk factors for residual low back pain (P < 0.05). The ROC and calibration curve of the original model and temporal external validation indicated a good predictive power of the model. The DCA curve suggested that the model has good clinical practicability. CONCLUSION: The risk prediction model has good predictive performance and clinical practicability, which can provide a certain basis for clinical decision-making in patients with OVCFs.

Rat Bone Mesenchymal Stem Cell-Derived Exosomes Loaded with miR-494 Promoting Neurofilament Regeneration and Behavioral Function Recovery after Spinal Cord Injury.

Exosomes (Exo) exhibit numerous advantages (e.g., good encapsulation, high targeting efficiency, and easy to penetrate the blood-brain barrier to the central nervous system). Exosomes are recognized as prominent carriers of mRNAs, siRNAs, miRNAs, proteins, and other bioactive molecules. As confirmed by existing studies, miR-494 is important to regulate the occurrence, progression, and repair of spinal cord injury (SCI). We constructed miR-494-modified exosomes (Exo-miR-494). As indicated from related research in vitro and vivo, Exo-miR-494 is capable of effectively inhibiting the inflammatory response and neuronal apoptosis in the injured area, as well as upregulating various anti-inflammatory factors and miR-494 to protect neurons. Moreover, it can promote the regeneration of the neurofilament and improve the recovery of behavioral function of SCI rats.

SiRNA in MSC-derived exosomes silences CTGF gene for locomotor recovery in spinal cord injury rats.

BACKGROUND: How to obtain a small interfering RNA (siRNA) vector has become a moot point in recent years. Exosomes (Exo) show advantages of long survival time in vivo, high transmission efficiency, and easy penetration across the blood-spinal cord barrier, renowned as excellent carriers of bioactive substances. METHODS: We applied mesenchymal stem cell (MSC)-derived exosomes as the delivery of synthesized siRNA, which were extracted from rat bone marrow. We constructed exosomes-siRNA (Exo-siRNA) that could specifically silence CTGF gene in the injury sites by electroporation. During the administration, we injected Exo-siRNA into the tail vein of SCI rats, RESULTS: In vivo and in vitro experiments showed that Exo-siRNA not only effectively inhibited the expressions of CTGF gene, but quenched inflammation, and thwarted neuronal apoptosis and reactive astrocytes and glial scar formation. Besides, it significantly upregulated several neurotrophic factors and anti-inflammatory factors, acting as a facilitator of locomotor recovery of rats with spinal cord injury (SCI). CONCLUSIONS: In conclusion, this study has combined the thoroughness of gene therapy and the excellent drug-loading characteristics of Exo for the precise treatment of SCI, which will shed new light on the drug-loading field of Exo.

Clinical Benefit of Rehabilitation Training in Spinal Cord Injury: A Systematic Review and Meta-Analysis.

STUDY DESIGN: A systematic review and meta-analysis. OBJECTIVE: This study was performed to evaluate the effects of different rehabilitation interventions in spinal cord injury. SUMMARY OF BACKGROUND DATA: Several activity-based interventions have been widely applied in spinal cord injury in the past, but the effects of these rehabilitation exercises are controversial. METHODS: Publications were searched from databases (PubMed, Embase, Cochrane, the database of the U.S. National Institutes of Health and World Health Organization International Clinical Trials Registry Platform) using the searching terms like spinal cord injury, transcranial magnetic stimulation, functional electrical stimulation, activity-based therapy, and robotic-assisted locomotor training. Randomized controlled trials and controlled trials were included. The primary outcomes included functional upper/lower extremity independence, walking capacity, spasticity, and life quality of individuals with spinal cord injury. Meta-analysis was performed using Revman 5.0 software. RESULTS: Thirty-one articles were included. Meta-analysis showed that transcranial magnetic stimulation improved walking speed (95% confidence interval [CI] 0.01, 0.16) and lower extremity function (95% CI 1.55, 7.27); functional electrical stimulation significantly increased upper extremity independence (95% CI 0.37, 5.48). Robotic-assisted treadmill training improved lower extremity function (95% CI 3.44, 6.56) compared with related controls. CONCLUSION: Activity-based intervention like transcranial magnetic stimulation, functional electrical stimulation, and robotic-assisted treadmill training are effective in improving function in individuals with spinal cord injury.Level of Evidence: 1.

Clinical effectiveness of percutaneous vertebroplasty in conjunction with postoperative radiotherapy in the treatment of spinal metastases.

PURPOSE: This study aimed to evaluate the clinical effects of percutaneous vertebroplasty (PVP) combined with postoperative radiotherapy (RT) in the treatment of spinal metastases. METHODS: Nine patients (4 males and 5 females, mean age 59.56 years) with painful pathologic compression vertebral fractures caused by metastatic cancers of the spine (5 thoracic levels, 8 lumbar levels) were admitted to our hospital between July 17, 2016 and September 25, 2018. All patients were treated with PVP via bilateral pedicle approach combined with postoperative RT to treat metastatic lesions of the centrum. The clinical records of the patients were retrospectively analyzed. Patients' demographic features and medical conditions including the Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) and Imageology data were observed. RESULTS: Patients' mean VAS scores decreased from 8.67 ± 0.50 preoperatively to 1.78 ± 0.83 at 6 months after PVP. Moreover, the mean ODI score decreased from 74.07 ± 13.15 preoperatively to 31.87 ± 10.00 at 6 months after PVP. Significant improvement in the degree of pain and dysfunction among the enrolled patients were observed. Furthermore, the metastatic carcinoma lesion within the vertebral body was well controlled according to imaging. CONCLUSION: PVP in conjunction with postoperative RT is a good treatment strategy for vertebral compression fractures caused by metastases.

Fascaplysin Derivatives Are Potent Multitarget Agents against Alzheimer's Disease: in Vitro and in Vivo Evidence.

Alzheimer's disease (AD) is characterized by progressive neurodegeneration and impaired cognitive functions. Fascaplysin is a ß-carboline alkaloid isolated from marine sponge Fascaplysinopsis bergquist in 1988. Previous studies have shown that fascaplysin might act on acetylcholinesterase and ß-amyloid (Aß) to produce anti-AD properties. In this study, a series of fascaplysin derivatives were synthesized. The cholinesterase inhibition activities, the neuronal protective effects, and the toxicities of these compounds were evaluated in vitro. Compounds 2a and 2b, the two most powerful compounds in vitro, were further selected to evaluate their cognitive-enhancing effects in animals. Both 2a and 2b could ameliorate cognitive dysfunction induced by scopolamine or Aß oligomers without affecting locomotor functions in mice. We also found that 2a and 2b could prevent cholinergic dysfunctions, decrease pro-inflammatory cytokine expression, and inhibit Aß-induced tau hyperphosphorylation in vivo. Most importantly, pharmacodynamics studies suggested that 2b could penetrate the blood-brain barrier and be retained in the central nervous system. All these results suggested that fascaplysin derivatives are potent multitarget agents against AD and might be clinical useful for AD treatment.

9-Methylfascaplysin Is a More Potent Aß Aggregation Inhibitor than the Marine-Derived Alkaloid, Fascaplysin, and Produces Nanomolar Neuroprotective Effects in SH-SY5Y Cells.

ß-Amyloid (Aß) is regarded as an important pathogenic target for Alzheimer's disease (AD), the most prevalent neurodegenerative disease. Aß can assemble into oligomers and fibrils, and produce neurotoxicity. Therefore, Aß aggregation inhibitors may have anti-AD therapeutic efficacies. It was found, here, that the marine-derived alkaloid, fascaplysin, inhibits Aß fibrillization in vitro. Moreover, the new analogue, 9-methylfascaplysin, was designed and synthesized from 5-methyltryptamine. Interestingly, 9-methylfascaplysin is a more potent inhibitor of Aß fibril formation than fascaplysin. Incubation of 9-methylfascaplysin with Aß directly reduced Aß oligomer formation. Molecular dynamics simulations revealed that 9-methylfascaplysin might interact with negatively charged residues of Aß42 with polar binding energy. Hydrogen bonds and π⁻π interactions between the key amino acid residues of Aß42 and 9-methylfascaplysin were also suggested. Most importantly, compared with the typical Aß oligomer, Aß modified by nanomolar 9-methylfascaplysin produced less neuronal toxicity in SH-SY5Y cells. 9-Methylfascaplysin appears to be one of the most potent marine-derived compounds that produces anti-Aß neuroprotective effects. Given previous reports that fascaplysin inhibits acetylcholinesterase and induces P-glycoprotein, the current study results suggest that fascaplysin derivatives can be developed as novel anti-AD drugs that possibly act via inhibition of Aß aggregation along with other target mechanisms.