Peripheral nerve injuries represent one of the most common causes of permanent disabilities. Therapeutic electrical stimulation has been widely used in neural regeneration for decades. Combined with the implantation of a nerve cuff, several outcomes have proven effectiveness and feasibility in neuroprosthetic applications. However, the current electrical stimulation strategy fails to complete nerve repair. There is a lack of research on long‐term implantable nanogenerators in the neurostimulation scenario. Especially considering many disease models, those devices may not reach the in vitro simulative working setting. Thus, an implanted sciatic nerve stimulation system that spontaneously generates biphasic electric pulses in response to rats’ movement is developed. The electric signals generated by this device could stimulate injured sciatic nerve by cuff electrode. This work introduces an implantable self‐regulated neural electrical stimulation system generated by a contact separation triboelectric nanogenerator with a nerve cuff electrode and compares it with chronic therapeutic electrical stimulation for sciatic nerve restoration effect. Neural function restoration is observed in gait and histological analysis. Moreover, the upregulation of growth associated protein 43 can be a protentional target. This could have potential clinical application in facilitating closed‐loop energy harvesting for long‐term electrical stimulation.
Summary Stem cell transplantation, especially treatment with bone marrow mesenchymal stem cells (BMSCs), has been considered a promising therapy for the locomotor and neurological recovery of spinal cord injury (SCI) patients. However, the clinical benefits of BMSCs transplantation remain limited because of the considerably low viability and inhibitory microenvironment. In our research, low‐intensity pulsed ultrasound (LIPUS), which has been widely applied to clinical applications and fundamental research, was employed to improve the properties of BMSCs. The most suitable intensity of LIPUS stimulation was determined. Furthermore, the optimized BMSCs were transplanted into the epicenter of injured spinal cord in rats, which were randomized into four groups: (a) Sham group (n = 10), rats received laminectomy only and the spinal cord remained intact. (b) Injury group (n = 10), rats with contused spinal cord subjected to the microinjection of PBS solution. (c) BMSCs transplantation group (n = 10), rats with contused spinal cord were injected with BMSCs without any priming. (d) LIPUS‐BMSCs transplantation group (n = 10), BMSCs stimulated with LIPUS were injected at the injured epicenter after contusion. Rats were then subjected to behavioral tests, immunohistochemistry, and histological observation. It was found that BMSCs stimulated with LIPUS obtained higher cell viability, migration, and neurotrophic factors expression in vitro. The rate of apoptosis remained constant. After transplantation of BMSCs and LIPUS‐BMSCs postinjury, locomotor function was significantly improved in LIPUS‐BMSCs transplantation group with higher level of brain‐derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the epicenter, and the expression of neurotrophic receptor was also enhanced. Histological observation demonstrated reduced cavity formation in LIPUS‐BMSCs transplantation group when comparing with other groups. The results suggested LIPUS can improve BMSCs viability and neurotrophic factors expression in vitro, and transplantation of LIPUS‐BMSCs could promote better functional recovery, indicating possible clinical application for the treatment of SCI.
BackgroundThe correlation between serum concentration of neuron specific enolase (NSE), S100B, and the prognosis of patients with acute spinal cord injury (ASCI) remains controversial.Material/MethodsSixty patients with confirmed diagnosis of ASCI were recruited for this study from February 2015 to January 2017. The serum level of NSE and S100B were dynamically measured: on the day of injury and for 2 weeks. The 60 cases were divided into Group A (1 or more than 1 ASIA grade improved at 6 months after the injury) and Group B (ASIA grades changed <1 at 6 months after the injury). The serum level of the 2 groups were compared at different time points. And the prognostic value of serum NSE and S100B as biomarkers in patients with ASCI were calculated by Bayes theorem.ResultsThe serum levels of NSE in Groups A and B on the 2nd day of injury reached a peak at 66.80±13.76 g/L and 98.87±20.12 μg/L, respectively, and then declined gradually. On the 14th day of injury, the serum levels of NSE in both groups were 21.23±8.45 and 39.32±16.31 μg/L, respectively, which were much lower than those on the 2nd day (P<0.05). The serum levels of S100B in Groups A and B rose after the injury and reached a peak on the 4th day of injury. Then, the levels declined gradually to 1.14±0.64 and 1.97±0.98 μg/L, respectively, 2 weeks after the injury. Serum levels of NSE and S100B were good biomarkers for predicting the prognosis of ASCI patients with the sensitivity of 74.35% and 71.79%, the specificity of 71.43% and 66.67%. The cutoff value for serum NSE and S100B were 29.07 μg/L and 1.67 μg/L respectively. The AUCs were 0.78 (95% CI: 0.66–0.89) and 0.76 (95% CI: 0.63–0.89) respectively for serum NSE and S100B.ConclusionsSerum levels of NSE and S100B protein can reflect the degree of spinal cord injury and could be potential biomarkers for the prognosis of acute spinal cord injury.
Bone grafting is a good alternative for filling the inevitable void that is created following opening-wedge high tibial osteotomy (OWHTO). This systematic review and meta-analysis evaluated whether bone grafting is necessary for OWHTO and the successful outcomes of OWHTO using either autograft (AU) or allograft (AL). All analyzed studies were acquired from PubMed, Medline, Embase, CNKI, Google Scholar, and Cochrane Library. Data were independently extracted by two coauthors and were analyzed using RevMan5.3. Mean differences, odds ratios, and 95% confidence intervals were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle–Ottawa Scale were used to assess the risk of bias. In total, 10 studies were assessed including three randomized controlled trials and seven observational studies. The methodological quality of the trials ranged from low to high. The overall estimate demonstrated that the difference between OWHTO using AU and AL groups and OWHTO using no filling group was not statistically significant for the loss of correction, and complications, but OWHTO using no filling group statistically showed better knee society score. Pooled results of reoperations, lateral cortex breaches, complications, and clinical function assessments showed no significant difference between AU and AL materials. Using AL statistically reduced the operative time compared with using AU. OWHTO with or without bone graft does not affect postoperative complications. No loss of correction was observed due to the lack of bone grafting. In addition, OWHTO without bone graft performs better for postoperative clinical function assessment. Complications and clinical results of medial OWHTO were similar using AL and AU and neither reported a median loss of correction of following OWHTO. Compared with using AU, using AL avoids harvest site complications and reduces operative time. To sum up, OWHTO without any bone graft is recommended for medial unicompartmental osteoarthritis of the knee. Further large-sample, multicenter, high-quality, randomized controlled trials are warranted to verify the outcomes of this meta-analysis.
The aim of this study is to evaluate the safety and effectiveness in the treatment of thoracic aggressive vertebral hemangiomas (AVHs) with neurologic deficit by multiple surgical treatments.The clinical and radiographic data of 5 patients suffering from thoracic AVHs with neurologic deficit and treated by multiple surgical treatments, including percutaneous curved vertebroplasty (PCVP) combined with pedicle screw fixation and decompressive laminectomy, were reviewed and analyzed retrospectively.Five patients (3 women and 2 man, with a mean age of 57.40 ± 11.93) were diagnosed with AVHs from July 2010 to April 2016. All of them had objective neurologic deficit, myelopathy, and back pain. They underwent multiple surgical treatments and were followed-up for 12 to 23 months. At final follow-up, Frankel Grade D was achieved in all 5 patients. Patients were free from pain and neurologic symptoms, and the functional status was improved. No major complication was found.The treatment of AVHs with neurologic deficit is a challenge for surgeons. PCVP combined with pedicle screw fixation and decompressive laminectomy is safe and effective, and can be used for AVHs with neurologic deficit. Further studies with more samples are required to validate the effectiveness and safety of PCVP combined with pedicle screw fixation and decompressive laminectomy.
Human adult bone marrow-derived neural stemlike cells (MDNSCs) may serve as ideal seed cells for cell replacement therapy for human neurological disorders and injuries. However, the long-term safety of this cell population after transplantation must be thoroughly explored before clinical application, and tumorigenicity is a major concern. In this study, we generated MDNSCs capable of forming neurospherelike aggregates and with the potency to differentiate into neural lineage cells in vitro and investigated hundreds of cancer-related genes in MDNSCs in order to determine whether there were any characteristics that could help in the evaluation of their tumorigenic potential. According to the results of testing by PCR and DNA sequencing, there were no mutations at the frequent mutation sites of tumor-suppressor genes p53, p16, and Rb1. Of the 440 cancer-related genes covered by Oligo GEArray Human Cancer Microarray OHS-802, 63 were found to be significantly overexpressed compared with that in fresh normal human adult bone marrow depleted of red blood cells (RBCs). In particular, the overexpressed genes included those promoting cell proliferation and cell invasion and metastasis and members of several oncogenic signaling pathways. The overexpression of MYC, MMP2, Notch2, STC1, ITGA3, STAT5b, RhoC, and Wnt1 was also revealed by quantitative real-time RT-PCR. Because it has been shown that activation of some of these genes promote tumorigenesis, our findings highlight the need for further studies of long-term tumorigenicity in MDNSCs.
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