Mesenchymal stem cell-derived exosomes as a new drug carrier for the treatment of spinal cord injury: A review.

Spinal cord injury (SCI) is a devastating traumatic disease seriously impairing the quality of life in patients. Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible. Developing new approaches to regenerate the central nervous system is still the priority. Exosomes derived from mesenchymal stem cells (MSC-Exo) have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI, which are the key processes to rescue damaged spinal cord neurons and restore their functions. Nonetheless, MSC-Exo in SCI received scant attention. In this review, we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms. Furthermore, we also focus on the application of exosomes as drug carrier in SCI. In particular, it combs the advantages of exosomes as a drug carrier for SCI, imaging advantages, drug types, loading methods, etc., which provides the latest progress for exosomes in the treatment of SCI, especially drug carrier.

Flexible Organic Photovoltaic-Powered Hydrogel Bioelectronic Dressing With Biomimetic Electrical Stimulation for Healing Infected Diabetic Wounds.

Electrical stimulation (ES) is proposed as a therapeutic solution for managing chronic wounds. However, its widespread clinical adoption is limited by the requirement of additional extracorporeal devices to power ES-based wound dressings. In this study, a novel sandwich-structured photovoltaic microcurrent hydrogel dressing (PMH dressing) is designed for treating diabetic wounds. This innovative dressing comprises flexible organic photovoltaic (OPV) cells, a flexible micro-electro-mechanical systems (MEMS) electrode, and a multifunctional hydrogel serving as an electrode-tissue interface. The PMH dressing is engineered to administer ES, mimicking the physiological injury current occurring naturally in wounds when exposed to light; thus, facilitating wound healing. In vitro experiments are performed to validate the PMH dressing's exceptional biocompatibility and robust antibacterial properties. In vivo experiments and proteomic analysis reveal that the proposed PMH dressing significantly accelerates the healing of infected diabetic wounds by enhancing extracellular matrix regeneration, eliminating bacteria, regulating inflammatory responses, and modulating vascular functions. Therefore, the PMH dressing is a potent, versatile, and effective solution for diabetic wound care, paving the way for advancements in wireless ES wound dressings.

Prognostic factors and treatment outcomes of spinal osteosarcoma: Surveillance, epidemiology, and end results database analysis.

Objective: Spinal osteosarcoma is a rare osseous neoplasm. The aim of this study is to make a comprehensive analysis of the demographic features, clinicopathologic characteristics and factors affecting prognosis of spinal osteosarcoma using the Surveillance, Epidemiology and End Results (SEER) database. Methods: SEER data were reviewed to identify patients diagnosed with spinal osteosarcoma between 1975 and 2016 and determine their overall survival (OS) and disease-specifc survival (DSS). Univariate and multivariate analyses were performed using the Cox-regression proportional hazards model and Kaplan-Meier method. Results: A total of 668 patients (53.1% males) with spinal osteosarcoma were identified. The mean age at diagnosis was 45.2 years, including 67.5% patients younger than 60 years. The median OS of these patients was 15 months, and the 5-year OS was 16.8%. Multivariate analysis showed that age ≥60 year (HR=2.271, p = 0.008), high grade (HR=1.323, p = 0.008), regional stage (HR=1.658, p = 0.017), metastasis stage (HR=3.045, p < 0.001) and no-surgery treatment (HR=1.761, p < 0.001) were adversely associated with OS; gender (HR=0.657, p = 0.044), tumor grade (HR=1.616, p = 0.006), tumor stage (HR=3.329, p = 0.011; HR=7.983, p < 0.001) and radiotherapy (HR=0.606, p = 0.031) were independent prognostic factors affecting DSS. Conclusion: Based on SEER data analysis, male, high tumor grade, regional stage, metastasis stage and radiotherapy are independent predictors of poor survival of patients with spinal osteosarcoma. The clinical treatment of spinal osteosarcoma still faces serious challenges. Future research should focus on the clinical impact and survival outcomes of the emerging targeted and immune therapies for the sake of improving the survival stalemate of spinal osteosarcoma.

RNA N6-methyladenosine demethylase FTO promotes osteoporosis through demethylating Runx2 mRNA and inhibiting osteogenic differentiation.

As a systemic disease, osteoporosis (OP) results in bone density loss and fracture risk, particularly in the hip and vertebrae. However, the underlying molecular mechanisms of OP development have not been fully illustrated. N6-Methyladenosine (m6A) is the most abundant modification of mRNAs, which is involved in many of pathological processes in aging disease. However, its role and regulatory mechanism in OP remains unknown. Here, we aimed to investigate the roles of m6A and its demethylase FTO in OP development. The results showed that m6A methylated RNA level was up-regulated in the bone marrow mesenchymal stem cells (BMSCs) from patients with OP. The level of N6-methyladenosine demethylase FTO was consistently decreased in the BMSCs from patients with OP. Functionally, lentivirus-mediated FTO overexpression in normal BMSCs to compromised osteogenic potential. Mechanism analysis further suggested that FTO overexpression decreased the m6A methylated and total level of runt related transcription factor 2 (Runx2) mRNA, subsequently inhibited osteogenic differentiation. We found that FTO inhibition could effectively improve the bone formation in ovariectomized osteoporotic mice in vivo. Together, these results reveal that RNA N6-methyladenosine demethylase FTO promotes osteoporosis through demethylating runx2 mRNA and inhibiting osteogenic differentiation.

miR-195-5p is critical in REGγ-mediated regulation of wnt/ß-catenin pathway in renal cell carcinoma.

Renal cell carcinoma (RCC) is the most prevalent malignancy of kidney and accounts for approximately 4% of all cancer diagnoses in adults. Previous studies demonstrated microRNA-195-5p (miR-195-5p) as a tumor suppressor which is deregulated in many human cancers. However, the role of miR-195-5p in RCC is largely unknown. In the present study, we demonstrated that miR-195-5p was downregulated and negatively correlated with advanced clinical stage in RCC. Overexpression of miR-195-5p significantly suppressed RCC cells growth in vitro and in vivo, induced apoptosis and enhanced chemosensitivity to sorafenib. Conversely, suppression of miR-195-5p exhibited a reverse effect. REGγ, a proteasome activator, was identified as a novel downstream target of miR-195-5p in RCC. Knockdown of REGγ inhibited proliferation, induced apoptosis, increased sorafenib chemosensitivity and suppressed the wnt/ß-catenin pathway in RCC cells. Moreover, restoration of REGγ markedly abolished the effects of miR-195-5p in RCC, and the wnt/ß-catenin pathway was suppressed by miR-195-5p overexpression while activated by miR-195-5p inhibition in RCC cells. Our findings suggest that miR-195-5p is critical in REGγ-mediated regulation of wnt/ß-catenin pathway in RCC development and may serve as a novel target for RCC treatment.

HIF-1α activates hypoxia-induced BCL-9 expression in human colorectal cancer cells.

B-cell CLL/lymphoma 9 protein (BCL-9), a multi-functional co-factor in Wnt signaling, induced carcinogenesis as well as promoting tumor progression, metastasis and chemo-resistance in colorectal cancer (CRC). However, the mechanisms for increased BCL-9 expression in CRC were not well understood. Here, we report that hypoxia, a hallmark of solid tumors, induced BCL-9 mRNA expression in human CRC cells. Analysis of BCL-9 promoter revealed two functional hypoxia-responsive elements (HRE-B and HRE-C) that can be specifically bound with and be transactivated by hypoxia inducible factors (HIF) -1α but not HIF-2α. Consistently, ectopic expression of HIF-1α but not HIF-2α transcriptionally induced BCL-9 expression levels in cells. Knockdown of endogenous HIF-1α but not HIF-2α by siRNA largely abolished the induction of HIF by hypoxia. Furthermore, there was a strong association of HIF-1α expression with BCL-9 expression in human CRC specimens. In summary, results from this study demonstrated that hypoxia induced BCL-9 expression in human CRC cells mainly through HIF-1α, which could be an important underlying mechanism for increased BCL-9 expression in CRC.

En Bloc Resection of Primary Malignant Bone Tumor in the Cervical Spine Based on 3-Dimensional Printing Technology.

OBJECTIVE: To investigate the feasibility and safety of en bloc resection of cervical primary malignant bone tumors by a combined anterior and posterior approach based on a three-dimensional (3-D) printing model. METHODS: Five patients with primary malignant bone tumors of the cervical spine underwent en bloc resection via a one-stage combined anteroposterior approach in our hospital from March 2013 to June 2014. They comprised three men and two women of mean age 47.2 years (range, 26-67 years). Three of the tumors were chondrosarcomas and two chordomas. Preoperative 3-D printing models were created by 3-D printing technology. Sagittal en bloc resections were planned based on these models and successfully performed. A 360° reconstruction was performed by spinal instrumentation in all cases. Surgical margins, perioperative complications, local control rate and survival rate were assessed. RESULTS: All patients underwent en bloc excision via a combined posterior and anterior approach in one stage. Mean operative time and estimated blood loss were 465 minutes and 1290 mL, respectively. Mean follow-up was 21 months. Wide surgical margins were achieved in two patients and marginal resection in three; these three patients underwent postoperative adjuvant radiation therapy. One vertebral artery was ligated and sacrificed in each of three patients. Nerve root involved by tumor was sacrificed in three patients with preoperative upper extremity weakness. One patient (Case 3) had significant transient radiculopathy with paresis postoperatively. Another (Case 4) with C 4 and C 5 chordoma had respiratory difficulties and pneumonia after surgery postoperatively. He recovered completely after 2 weeks' management with a tracheotomy tube and antibiotics in the intensive care unit. No cerebrovascular complications and wound infection were observed. No local recurrence or instrumentation failure were detected during follow-up. CONCLUSION: Though technically challenging, it is feasible and safe to perform en bloc resection of cervical primary bone tumors. This is the most effective means of managing cervical spine tumors. Preoperative 3-D printing modelling enables better anatomical understanding of the relationship between the tumor and cervical spine and can assist in planning the surgical procedure.

Minimally invasive treatment for Neer IIb distal clavicle fractures with titanium cable.

BACKGROUND: Neer IIB distal clavicle fracture is associated with disruption of the coracoclavicular ligament and a variable degree of displacement. Surgical treatment using various implants such as intramedullary wires, screws, and plates has been described in the literature with satisfactory results. METHODS: We report our experience of minimally invasive treatment using titanium cable for type IIB clavicular fractures. A retrospective analysis was performed to evaluate the outcomes of patients with Neer IIB distal clavicle fractures that were treated with titanium cable between 2003 and 2008. Functional outcome was evaluated using the Karlsson's criteria. The mean follow-up was 32 months (range, 12-48 months). Twenty-nine patients met the inclusion criteria. RESULTS: All patients progressed to osseous union at a mean time of 12 weeks (range, 10-15 weeks). There was one metal work failure that did not affect functional recovery. According to Karlsson's criteria, radiographic representations (3 months after surgery) and postoperative shoulder functional recovery revealed an excellent and good rate in all cases. CONCLUSION: Minimally invasive surgery using titanium cable seems to be a good option for the treatment of Neer IIB distal clavicle fractures, with early functional recovery and no requirement for revision surgery.

[Effective analysis of the posterior vertebral pedicle screw fixation, vertebral body removal, decompression and titanium mesh reconstruction for the treatment of the lower lumbar fractures].

OBJECTIVE: To evaluate the effect of the treatment of the lower lumbar fractures by posterior vertebral pedicle screw fixation, vertebral canal decompression,bone graft and titanium mesh reconstruction. METHODS: From January 2006 to December 2008, 22 patients with lower lumbar fractures were treated by posterior vertebral pedicle screw fixation, vertebral canal decompression, bone graft and titanium mesh reconstruction at same period. There were 18 males and 4 females with an average age of 43.8 years ranging from 22 to 63 years old. The injured vertebrae were L3 in 11 cases, L4, in 8 cases, and L5 in 3 cases. The operative time, blood loss, the preoperative and postoperative vertebral height,sagittal index, and the lumbar lordosis angle were recorded and evaluated. RESULTS: The operative time was 3 to 4.2 hours (means 3.6 h). The blood loss averaged 1300 ml (900 to 1500 ml). The preoperative and postoperative sagittal index were (57.5 +/- 7.6)% and (93.5 +/- 8.1)%, respectively. The preoperative and postoperative lumbar lordosis angle were (34.3 +/- 7.3) degrees and (38.5 +/- 9.8) degrees, respectively. All patients were followed up for 10 months to 3 years (means 2.6 years). No fixation were failed,the segment of titanium mesh reconstruction obtained bone healing, no pseudoarticulation formation. At the last time of followed-up, 15 patients with nerve injuries were evaluated according to Frankel grade, there were 10 cases in grade E, 4 in D, 1 in C. According to the low back outcome scores (LBOS), the results were excellent in 20 cases, good in 1, fair in 1. CONCLUSION: The stability of the lower lumbar spine can be reconstructed by bone graft and titanium mesh combined with transpedicular screw fixation through a posterior approach. The decompression and vertebral body removal can also be performed in this approach. The recovery of the vertebral height and lumbar lordosis can prevent the delayed neurological deficit and traumatic kyphosis.

[Biomechanical performance of different wires and cable fixation devices in posterior instrumentation for atlantoaxial instability].

OBJECTIVE: To compare the biomechanical performances of different wires and cable fixation devices in posterior instrumentation for atlantoaxial instability, and test the effect of different fixation strengths and fixation approaches on the surgical outcomes. METHODS: Six specimens of the atlantoaxial complex (C0-C3) were used to establish models of the normal complex, unstable complex (type II odontoid fracture) and fixed complex. On the wd-5 mechanical testing machine, the parameters including the strength and rigidity of anti-rotation, change and strength of stress, and stability were measured for the normal complex, atlantoaxial instability complex, the new type titanium cable fixation system, Atlas titanium cable, Songer titanium cable, and stainless wire. RESULTS: The strength and rigidity of anti-rotation, change and strength of stress, stability of flexion, extension and lateral bending of the unstable atlantoaxial complex fixed by the new double locking titanium cable fixation system were superior to those of the Songer or Atlas titanium cable (P<0.05) and medical stainless wire (P<0.05). Simultaneous cable fastening on both sides resulted in better fixation effect than successive cable fastening (P<0.05). Better fixation effect was achieved by fastening the specimen following a rest (P<0.05). CONCLUSIONS: The fixation effects can be enhanced by increased fastening strengths. The new type double locking titanium cable fixation system has better biomechanical performance than the conventional Songer and Atlas titanium cables. Fastening the unstable specimens after a rest following simultaneous fastening of the specimen on both sides produces better fixation effect.

[Anti-rotation biomechanical study of wire and various cable system in the posterior brooks instrumentation for atlantoaxial instability].

OBJECTIVE: To compare the anti-rotation biomechanical performances of wire and various cable fixation devices currently used in the posterior Brooks instrumentation for atlantoaxial instability. METHODS: In this experiment,six specimens of the atlantoaxial complex (Occipital-C3) were used. The models of the normal complex,unstable complex (type II odontoid fracture) and fixed complex were established. On the WD-5 mechanics experimental machine,the parameters including the strength and rigidity of anti-rotation were quantified for the normal complex (group N),the atlantoaxial instability complex (group M), the new type Titanium cable (group A), Atlas titanium cable (group B), Songer Titanium cable (group C), stainless wire(group D). RESULTS: The max strength of A, B, C, D groups was 12.5, 11.3, 11.52, 11.55 N x m respectively, the max rigidity was 58.81, 53.17, 54.11, 54.35 N x cm/deg respectively. The strength and rigidity of anti-rotation, compare to the unstable atlantoaxial complex which were fixed by the new double locking Titanium cable fixation system were superior to those of normal complex, instability complex, Songer or Atlas Titanium cable (P < 0.05). CONCLUSION: Having been changed the locking method, the anti-rotation biomechanical characteristics of the new type double locking Titanium cable fixation system are superior or similar to the traditional Songer or Atlas Titanium cable.

[Clinical characteristics and diagnosis of rheumatoid arthritis of upper cervical spine: analysis of 71 cases].

OBJECTIVE: To study the clinical characteristics and diagnosis of rheumatoid arthritis (RA) in the upper cervical spine. METHODS: The clinical data of 71 patients with RA in the upper cervical spine, 18 males and 53 females, aged 46.2 (23-76), with a mean duration of RA of 18.2 years (2 months-47 years) were retrospectively reviewed. Fifty-three patients received glucocorticoid for more than 3 months. In addition to routine examinations, all patients underwent plain X-ray film taking, CT and MRI scanning, and erythrocyte sedimentation rate, rheumatoid factor (RF) and antistreptolysin O testing. RESULTS: The symptoms of upper cervical spine appeared at 8.3 years (2 months-46 years) after the diagnosis of RA was confirmed. The clinical manifestations of RA in the upper cervical spine were intractable pain in craniocervical junction or radiating pain. Abnormal postures in the neck and Sherp-Purser's sign were positive in some patients. Progressive neurological dysfunction with the involvement of spinal cord, medulla, or some cranial nerves might gradually appear. Irregular destruction of bone with osteoporosis around the lateral and median atlantoaxial joint was a common finding in the X-ray films and CT scans. Instability of the atlantoaxial joint, including anterior atlantoaxial subluxation, posterior atlantoaxial subluxation and anterior-posterior atlantoaxial subluxation were found in 68 cases, while rotation subluxation was presented in 37 cases. Vertical migration of the odontoid was seen in 11 cases. RF was positive in 18 cases. MRI revealed that the cause of spinal cord compression was the bone tissue and soft tissue pannus. CONCLUSIONS: RA in the upper cervical spine is a common situation in the clinical settings. The key point in the diagnosis of this disease is the identification of instability in the atlantoaxial joint and assessment of the spinal neurological deficit. And a careful analysis of the natural history will further help to achieve a better treatment effect.