Ropivacaine microsphere-loaded electroconductive nerve dressings for long-acting analgesia and functional recovery following diabetic peripheral nerve injury.

In recent years, electroconductive hydrogels (ECHs) have shown great potential in promoting nerve regeneration and motor function recovery following diabetic peripheral nerve injury (PNI), attributed to their similar electrical and mechanical characteristics to innate nervous tissue. It is well-established that PNI causes motor deficits and pain, especially in diabetics. Current evidence suggests that ropivacaine (ROP) encapsulated in poly lactic-co-glycolic acid (PLGA) microspheres (MSs) yield a sustained analgesic effect. In this study, an ECH electroconductive network loaded with MS/ROP (ECH-MS/ROP) was designed as a promising therapeutic approach for diabetic PNI to exert lasting analgesia and functional recovery. This dual delivery system allowed ROP's slow and sequential release, achieving sustained analgesia as demonstrated by our in vivo experiments. Meanwhile, this system was designed like a lamellar dressing, with desirable adhesive and self-curling properties, convenient for treating injured nerve tissues via automatically wrapping tube-like structures, facilitating the process of implantation. Our in vitro assays verified that ECH-MS/ROP was able to enhance the adhesion and motility of Schwann cells. Besides, both in vitro and in vivo studies substantiated that ECH-MS/ROP stimulated myelinated axon regeneration through the MEK/ERK signaling pathway, thereby improving muscular denervation atrophy and facilitating functional recovery. Therefore, this study suggests that the ECH-MS/ROP dressing provides a promising strategy for treating diabetic PNI to facilitate nerve regeneration, functional recovery and pain relief.

Lumbar facet joint osteoarthritis as the underlying reason for persistent low back pain after minimally invasive discectomy.

INTRODUCTION: A post-hoc subgroup analysis of prospective collected data in a randomized controlled trial (RCT) of minimally invasive discectomy was conducted, to find out the possible underlying reasons for patients with persistent low back pain (LBP) following surgery. MATERIALS AND METHODS: Patients who were diagnosed with lumbar disc herniation (LDH) and underwent either percutaneous transforaminal endoscopic discectomy or microendoscopic discectomy in our RCT were analyzed. Patients with persistent LBP in 2-year follow-up were compared with the non-LBP patients to determine the underlying reasons. Then, the demographic characteristics, clinical outcomes and radiological parameters of patients with preoperative lumbar facet joint osteoarthritis (LFJOA) were assessed and compared with the non-LFJOA subgroup. RESULTS: 18 patients (8.1%) were reported to have persistent LBP in 2-year follow-up. Significantly higher proportion of preoperative LFJOA were found in the persistent LBP subgroup and was considered to be a risk factor using multivariate analysis. The prevalence of LFJOA is strongly associated with older age, female, high BMI and heavy labor in the LDH population. All of the clinical outcomes including ODI, SF36-PF, SF36-BP, EQ-5D, VAS-back and VAS-leg were worse in LFJOA subgroup in 2-year follow-up. LFJOA subgroup was associated with more adjacent segment degeneration and more lateral recess stenosis. CONCLUSIONS: LFJOA is a possible underlying reason for patients with persistent LBP after minimally invasive discectomy. Surgeons should carefully review the preoperative radiological images to find out whether there is LFJOA in the LDH segment, and kindly diminish the expectation of back pain relief for those patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov at November 14, 2013, registration number NCT01997086. ( https://clinicaltrials.gov/ct2/show/NCT01997086 ).

Percutaneous Transforaminal Endoscopic Discectomy Versus Microendoscopic Discectomy for Lumbar Disk Herniation: Five-year Results of a Randomized Controlled Trial.

STUDY DESIGN: A prospective randomized controlled study. OBJECTIVE: To compare the efficacy and safety between percutaneous transforaminal endoscopic discectomy (PTED) and microendoscopic discectomy (MED). SUMMARY OF BACKGROUND DATA: Two kinds of minimally invasive discectomy, PTED and MED, are now widely used for treating lumbar disk herniation (LDH). The long-term comparative results of these two techniques still remained uncertain. MATERIALS AND METHODS: In this single-center, open-label, randomized controlled trial, patients were included if they had persistent signs and symptoms of radiculopathy with corresponding imaging-confirmed LDH and were randomly allocated to PTED or MED groups. The primary outcome was the score of Oswestry Disability Index (ODI) and the secondary outcomes included the score of Medical Outcomes Study 36-Item Short-Form Health Survey bodily pain (SF36-BP) and physical function (SF36-PF), European Quality of Life-Five Dimensions (EQ-5D), Visual Analog Scales for back pain (VAS-back) and leg pain (VAS-leg). RESULTS: A total of 241 patients were accepted to enroll in our randomized controlled trial, of which 119 were randomly assigned to the PTED group, and the rest 122 were assigned to the MED group. A total of 194 out of 241 patients (80.5%) completed the five-year follow-up. PTED group was associated with shorter postoperative in-bed time and length of hospital stay. Both primary and secondary outcomes did not differ significantly between the two treatment groups at each follow-up time point. During the five-year follow-up, seven recurrent cases occurred in PTED and MED groups, respectively. CONCLUSION: Over the five-year follow-up period, PTED and MED were both efficacious in the treatment of LDH. The long-term clinical outcomes and recurrent rates were comparable between the treatment groups. PTED represents a more minimally invasive technique with the advantages of rapid recovery.

Determination of Patient Acceptable Symptom State for the Oswestry Disability Index Score in Patients Who Underwent Minimally Invasive Discectomy for Lumbar Disc Herniation: 2-Year Follow-up Data from a Randomized Controlled Trial.

OBJECTIVE: We aim to determinate the patient acceptable symptom state (PASS) for the Oswestry Disability Index (ODI) score in patients undergoing minimally invasive discectomy for the treatment of lumbar disc herniation. METHODS: A post hoc analysis of prospectively collected, 2-year follow-up data was conducted. The anchor for determination of PASS was the European Quality of Life Visual Analog Scales question, and the Pearson correlation test was performed to evaluate its validity. The receiver operating characteristics (ROC) curve analysis was conducted to determine the PASS thresholds for ODI and its discriminative ability assessment. Sensitivity analyses were also carried out for alternative definition of PASS, different follow-up periods, and different subgroups. RESULTS: A total of 222 patients (92.1%) completed the 2-year follow-up, 92.8% of whom considered their state to be acceptable. The area under the ROC curve (AUC) were all >0.8, indicating a high discriminative ability. The PASS threshold for the ODI was suggested to be 5 at 6 months (AUC: 0.80; sensitivity: 79.0%, specificity: 73.7%) and 2 years (AUC: 0.98; sensitivity: 90.3%, specificity: 100%) postoperatively. Despite some variations found in different body mass index and baseline ODI subgroups, sensitivity analysis showed that the above-mentioned threshold was robust. CONCLUSIONS: An ODI of 5 was noted to be the PASS threshold for patients received minimally invasive discectomy for the treatment of LDH. This ODI threshold was robust, and therefore recommended as the ultimate goal of minimally invasive treatment for LDH, which can help to present results of clinical research at an individual level.

Comparative Efficacy and Safety of 11 Drugs as Therapies for Adults With Neuropathic Pain After Spinal Cord Injury: A Bayesian Network Analysis Based on 20 Randomized Controlled Trials.

Objective: To provide an updated analysis of the efficacy and safety of drugs for the management of neuropathic pain (NP) after spinal cord injury (SCI) based on Bayesian network analysis. Methods: A Bayesian network meta-analysis of literature searches within PubMed, Cochrane Library, Embase, and Web of Science databases from their inception to February 21 2021 was conducted without language restrictions. Paired and network meta-analyses of random effects were used to estimate the total standardized mean deviations (SMDs) and odds ratios (ORs). Results: A total of 1,133 citations were identified and 20 RCTs (including 1,198 patients) involving 11 drugs and placebos for post-SCI NP selected. The 5 outcomes from all 11 drugs and placebos had no inconsistencies after Bayesian network analysis. BTX-A gave the most effective pain relief for the 4 weeks, following a primary outcome. No significant differences were found among drugs with regard to adverse events of the primary outcome. Gabapentin, BTX-A, and pregabalin were found to be the most helpful in relieving secondary outcomes of mental or sleep-related symptoms with differences in SMDs, ranging from -0.63 to -0.86. Tramadol triggered more serious adverse events than any of the other drugs with differences in ORs ranging from 0.09 to 0.11. Conclusion: BTX-A, gabapentin, pregabalin, amitriptyline, ketamine, lamotrigine, and duloxetine were all effective for NP management following SCI. Lamotrigine and gabapentin caused fewer side effects and had better efficacy in relieving mental or sleep-related symptoms caused by SCI-related NP. Tramadol, levetiracetam, carbamazepine, and cannabinoids could not be recommended due to inferior safety or efficacy. Systematic Review Registration: [https://inplasy.com/inplasy-2020-7-0061/], identifier [INPLASY202070061].

Risk Factors for Poor Outcomes Following Minimally Invasive Discectomy: A Post Hoc Subgroup Analysis of 2-Year Follow-up Prospective Data.

OBJECTIVE: A post hoc subgroup analysis of prospectively collected data from a randomized controlled trial was conducted to identify risk factors related to poor outcomes in patients who underwent minimally invasive discectomy. METHODS: Patients were divided into satisfied and dissatisfied subgroups based on Oswestry Disability Index (ODI), visual analogue scale (VAS) back pain score (VAS-back) and leg pain score (VAS-leg) at short-term and midterm follow-up according to the patient acceptable symptom state threshold. Demographic characteristics, radiographic parameters, and clinical outcomes between the satisfied and dissatisfied subgroups were compared using univariate and multivariate analysis. RESULTS: A total of 222 patients (92.1%) completed 2-year follow-up, and the postoperative ODI, VAS-back, and VAS-leg were significantly improved after surgery as compared to preoperatively. Multivariate analysis indicated older age (p = 0.026), lateral recess stenosis (p = 0.046), and lower baseline ODI (p = 0.027) were related to poor short-term functional improvement. Higher baseline VAS-back (p = 0.048) was associated with poor short-term relief of back pain, while absence of decreased sensation (p = 0.019) and far-lateral disc herniation (p = 0.004) were associated with poorer short-term relief of leg pain. Lumbar facet joint osteoarthritis was identified as a risk factor for poor functional improvement (p = 0.003) and relief of back pain (p = 0.031). Disc protrusion (p = 0.036) predicted poorer relief of back pain at midterm follow-up. CONCLUSION: In this study, several factors were identified to be predictive of poor surgical outcomes following minimally invasive discectomy. (ClinicalTrials.gov number: NCT01997086).

Potential Application of MR-MR-US Fusion Imaging Navigation with Needle Tail Intelligent Positioning in Guiding Puncture in Percutaneous Transforaminal Endoscopic Discectomy.

This study sought to investigate the feasibility of using magnetic resonance-magnetic resonance-ultrasound (MR-MR-US) fusion imaging navigation (FIN) with needle tail intelligent positioning (NTIP) to guide puncture in percutaneous transforaminal endoscopic discectomy (PTED). First, in a pig experiment, we found that puncture errors in lumbar intervertebral foramen (LIF) puncture using magnetic resonance-magnetic resonance-ultrasound (MR-MR-US) FIN with NTIP for experienced and novice operators were 2.00 ± 1.00 and 2.57 ± 0.98 mm, respectively (p = 0.231), suggesting this technique was minimally dependent on experience. Then, two experienced surgeons agreed (inter-observer agreement к=0.801) that the quality of MR-MR fusion images was good or sufficient. Finally, we performed PTED in eight patients using MR-MR-US FIN with NTIP, and no significant complications were reported during LIF puncture. Overall, MR-MR-US FIN with NTIP may be a potential application for guiding puncture in PTED, but more clinical studies with a larger sample size are required to further evaluate the advantages of MR-MR-US FIN with NTIP.

Melatonin contributes to the hypertrophic differentiation of mesenchymal stem cell-derived chondrocytes via activation of the Wnt/ß-catenin signaling pathway : Melatonin promotes MSC-derived chondrocytes hypertrophy.

BACKGROUND: Hypertrophy is a critical process for chondrocyte differentiation and maturation during endochondral ossification, which is responsible for the formation of long bone and postnatal longitudinal growth. Increasing evidence suggests that melatonin, an indole hormone, plays a pivotal role in chondrogenesis. However, little is known about the effects of melatonin on the terminal differentiation of chondrocytes. METHODS: Mesenchymal stem cell (MSC)-derived chondrocytes generated by a high-density micromass culture system were induced to undergo hypertrophic differentiation. Melatonin-mediated hypertrophic differentiation was examined by reverse transcription polymerase chain reaction analysis (RT-PCR) analysis, histological staining and immunohistochemistry. Activation of the Wnt signaling pathway was evaluated by PCR array, RT-PCR, western blotting and immunofluorescence. XAV-939, a Wnt signaling pathway antagonist, was further used to determine whether the effect of melatonin on chondrocyte hypertrophic differentiation was mediated occurred by activation of Wnt signaling pathway. RESULTS: Histological staining showed melatonin increased chondrocyte cell volume and the expression of type X collagen but decreased the expression of type II collagen compared with the control group. RT-PCR showed that melatonin significantly up-regulated the gene expressions of biomarkers of hypertrophic chondrocytes, including type X collagen, alkaline phosphatase, runt-related transcription factor 2, Indian hedgehog and parathyroid hormone-related protein receptor, and melatonin down-regulated the mRNA expression of hallmarks of chondrocytes, including parathyroid hormone-related protein. PCR array showed that the effect of melatonin on chondrocyte hypertrophic differentiation was accompanied by the up-regulation of multiple target genes of the canonical Wnt signaling pathway, and this effect was blocked by XAV-939. CONCLUSIONS: The current findings demonstrate that melatonin enhances the hypertrophic differentiation of MSC-derived chondrocytes through the Wnt signaling pathway. Our findings add evidence to the role of melatonin in promoting bone development and highlight the positive effects of melatonin on terminal differentiation of chondrocytes.

Identification of HCG18 and MCM3AP-AS1 That Associate With Bone Metastasis, Poor Prognosis and Increased Abundance of M2 Macrophage Infiltration in Prostate Cancer.

BACKGROUND: Bone metastasis is a leading cause of the high mortality rate of prostate cancer (PCa), but curative strategies remain lacking. Recent studies suggest long non-coding RNAs (lncRNAs) may be potential targets to develop drugs. However, PCa bone metastasis-specifically-related lncRNAs were rarely reported. This study aimed to identify crucial lncRNAs and reveal their function mechanisms. METHODS: GSE32269 and GSE26964 microarray datasets, downloaded from the Gene Expression Omnibus database, were used to analyze differentially expressed genes (DEGs)/lncRNAs (DELs) and miRNAs (DEMs), respectively. Weighted gene co-expression network analysis was performed to screen PCa bone metastasis-associated modules. The co-expression and competing endogenous RNAs (ceRNAs) networks were constructed to identify hub lncRNAs. Univariate Cox regression analysis was conducted to determine their prognostic values. The correlation of lncRNAs with immune infiltrating cells was analyzed by using Tumor IMmune Estimation Resource. Therapeutic drugs were predicted by querying the Connectivity Map (CMap) and the Comparative Toxicogenomics Database (CTD). RESULTS: A total of 18 DELs, 2,614 DEGs and 86 DEMs were screened between bone metastatic and primary PCa samples. Four modules enriched by DEGs were shown to be bone metastasis-associated. LncRNA HCG18 and MCM3AP-AS1 were identified to be important because they existed in both of the co-expression and ceRNA networks (forming the relationship pairs: HCG18/MCM3AP-AS1-KNTC1, MCM3AP-AS1-hsa-miR-508-3p-DTL and HCG18/MCM3AP-AS1-hsa-miR-127-3p-CDKN3). All the genes in these interaction pairs were significantly associated with overall survival of PCa patients. Also, HCG18, MCM3AP-AS1 and their target mRNAs were positively correlated with various tumor-infiltrated immune cells, especially increased M2 macrophages. Valproic acid and trichostatin A may be effective to treat PCa bone metastasis by targeting HCG18 and MCM3AP-AS1. CONCLUSION: HCG18 and MCM3AP-AS1 that regulate M2 macrophage infiltration may be important targets to treat PCa bone metastasis and improve prognosis.

Repeated subarachnoid administrations of allogeneic human umbilical cord mesenchymal stem cells for spinal cord injury: a phase 1/2 pilot study.

BACKGROUND AIMS: Stem cell transplantation is a potential treatment for intractable spinal cord injury (SCI), and allogeneic human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate because of the advantages of immune privilege, paracrine effect, immunomodulatory function, convenient collection procedure and little ethical concern, and there is an urgent need to develop a safe and effective protocol regarding their clinical application. METHODS: A prospective, single-center, single-arm study in which subjects received four subarachnoid transplantations of hUC-MSCs (1 × 106 cells/kg) monthly and were seen in follow-up four times (1, 3, 6 and 12 months after final administration) was conducted. At each scheduled time point, safety and efficacy indicators were collected and analyzed accordingly. Adverse events (AEs) were used as a safety indicator. American Spinal Injury Association (ASIA) and SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) total scores at the fourth follow-up were determined as primary efficacy outcomes, whereas these two indicators at the remaining time points as well as scores of pinprick, light touch, motor and sphincter, muscle spasticity and spasm, autonomic system, bladder and bowel functions, residual urine volume (RUV) and magnetic resonance imaging (MRI) were secondary efficacy outcomes. Subgroup analysis of primary efficacy indicators was also performed. RESULTS: Safety and efficacy assessments were performed on 102 and 41 subjects, respectively. Mild AEs involving fever (14.1%), headache (4.2%), transient increase in muscle tension (1.6%) and dizziness (1.3%) were observed following hUC-MSC transplantation and resolved thoroughly after conservative treatments. There was no serious AE. ASIA and IANR-SCIFRS total scores revealed statistical increases when compared with the baselines at different time points during the study, mainly reflected in the improvement of pinprick, light touch, motor and sphincter scores. Moreover, subjects showed a continuous and remarkable decrease in muscle spasticity. Regarding muscle spasm, autonomic system, bladder and bowel functions, RUV and MRI, data/imaging at final follow-up showed significant improvements compared with those at first collection. Subgroup analysis found that hUC-MSC transplantation improved neurological functions regardless of injury characteristics, including level, severity and chronicity. CONCLUSIONS: The authors' present protocol demonstrates that intrathecal administration of' allogeneic hUC-MSCs at a dose of 106 cells/kg once a month for 4 months is safe and effective and leads to significant improvement in neurological dysfunction and recovery of quality of life.

Percutaneous transforaminal full endoscopic decompression for the treatment of lumbar spinal stenosis.

BACKGROUND: One advantage of an endoscopic approach to treating lumbar spinal stenosis is preservation of spine stability and the adjacent anatomy, and there is a decrease in adjacent segment disc degeneration. The purpose of this study was to discuss the clinical efficacy of percutaneous transforaminal endoscopic decompression for the treatment of lumbar spinal stenosis (LSS). METHODS: This is a retrospective study. From September 2012 to June 2017, 45 patients who were diagnosed with LSS underwent the treatment of percutaneous transforaminal endoscopic decompression (PTED) and were followed up at 1 week, 3 months and 1 year postoperatively. Low back pain and leg pain were measured by Visual Analogue Scale scoring methods (VAS-back and VAS-leg), while functional outcomes were assessed by using the Oswestry Disability Index (ODI). All patients had one-level lumbar spinal stenosis. RESULTS: The most common type of stenosis was lateral recess stenosis (n = 22; 48.9%), followed by central stenosis (n = 13; 28.9%) and foraminal stenosis (n = 10: 22.2%). Regarding comparisons of VAS-back, VAS-leg, and ODI scores before and after operation, VAS and ODI scores significantly improved. The average leg VAS score improved from 7.01 ± 0.84 to 2.28 ± 1.43 (P < 0.001). The average ODI improved from 46.18 ± 10.11 to 14.40 ± 9.59 (P < 0.001). We also examined changes in ODI and VAS scores from baseline according to types of spinal stenosis, stenosis grade, spinal instability, and revision surgery in the same segment. The improvement percentage of leg VAS score was significantly less in patients with severe stenosis at both 3 months and 1 year postoperatively. The improvement percentages of ODI and leg VAS scores were significantly less in patients who had spinal instability and patients who had undergone revision surgery. CONCLUSION: The PTED approach seems to give good results for the treatment of LSS. However, this approach may be less effective for LSS patients who have lumbar instability or require revision surgery in the same segment.

Anterior cervical discectomy and fusion versus posterior cervical foraminotomy for the treatment of single-level unilateral cervical radiculopathy: a meta-analysis.

BACKGROUND: To compare the effectiveness and safety of anterior cervical discectomy and fusion (ACDF) with posterior cervical foraminotomy (PCF) for patients diagnosed with single-level unilateral cervical radiculopathy. METHODS: Relevant studies comparing ACDF with PCF for cervical radiculopathy were searched in an electronic database. After data extraction and quality assessment of included studies, a meta-analysis was done by using the RevMan 5.3 software. The random effects model was used if there was heterogeneity between studies; otherwise, the fixed effects model was used. RESULTS: A total of 3 randomized controlled trials (RCT) and 12 retrospective studies including 52705 patients were included in the meta-analysis. There were no significant differences in Neck Disability Index (NDI), Visual Analog Scale (VAS), and patients' satisfaction (P > 0.05) between treatment groups. The complication rate of the PCF group was equivalent compared with the ACDF group (P = 0.60), but the reoperation rate following PCF was on the higher side (P = 0.02). Data analysis also showed that the PCF group was associated with shorter operation time (P = 0.001) and shorter length of hospital stay (P = 0.002). CONCLUSIONS: Among patients with single-level unilateral cervical radiculopathy, PCF has comparable effectiveness and complication rate compared with ACDF. It seems that PCF is a sufficient alternative procedure with shorter operation time, shorter length of hospital stay, and less total hospital cost for the treatment of cervical radiculopathy. However, the higher reoperation rate following PCF should be also taken into consideration.

Real-time ultrasonography-magnetic resonance image fusion navigation for percutaneous transforaminal endoscopic discectomy.

OBJECTIVE: Percutaneous transforaminal endoscopic discectomy (PTED) is usually performed under fluoroscopic guidance and is associated with a large radiation dose. Ultrasonography (US)-MR image fusion navigation combines the advantages of US and MRI and requires significantly less radiation than fluoroscopy. The purpose of this study was to evaluate the safety and effectiveness of US-MR image fusion navigation for PTED. METHODS: From January to September 2018, patients with L4-5 lumbar disc herniation requiring PTED were randomized to have the procedure conducted with US-MR image fusion navigation or fluoroscopy. The number of fluoroscopies, radiation dose, duration of imaging guidance, intraoperative visual analog scale (VAS) pain score, intraoperative complications, and clinical outcomes were compared between the groups. RESULTS: There were 10 patients in the US-MR navigation group and 10 in the fluoroscopy group, and there were no significant differences in age, sex ratio, or BMI between the 2 groups (all p > 0.05). Intraoperatively, the total radiation dose, number of fluoroscopies performed, duration of image guidance, and VAS low-back and leg pain scores were all significantly lower in the US-MRI navigation group than in the fluoroscopy group (all p < 0.05). There were no intraoperative complications in either group. Postoperative improvements in Japanese Orthopaedic Association, Oswestry Disability Index, and VAS pain scale scores were similar between the 2 groups. CONCLUSIONS: US-MR image fusion navigation is a promising technology for performing PTED and requires significantly less radiation than fluoroscopy.Clinical trial registration no.: NCT03403244 (ClinicalTrials.gov).

Amyloid ß peptide promotes bone formation by regulating Wnt/ß-catenin signaling and the OPG/RANKL/RANK system.

BACKGROUND: Amyloid ß peptide (Aß) is involved in osteoporosis, but the effects of Aß on osteoblast and bone formation remain unclear. In this study, we investigated the effect of Aß on bone formation. METHODS: An animal model of osteoporosis was established by ovariectomy in C57BL/6 mice. The mice received intraperitoneal injection of Aß. The effect of Aß on the osteogenic differentiation of human bone marrow stromal stem cells (hBMSCs) and differentiation of both pre-osteoblasts and pre-osteoclasts in a co-culture system were investigated. RESULTS: In the animal study, intraperitoneal injection of Aß for 8 weeks promoted early and late osteogenic differentiation of hBMSCs. Aß treatment significantly elevated osterix+ (osteoblastic) cells but decreased TRAP+ cells (osteoclasts) in the distal femur bone. In vitro study showed that Aß treatment significantly enhanced matrix mineralization and osteogenic markers (Runx2 and osteocalcin). Aß treatment activated Wnt/ß-catenin signaling in hBMSCs. The effect of Aß was blocked by DKK1 (a Wnt/ß-catenin inhibitor) treatment. In the co-culture system, Aß treatment significantly increased the ALP activities of MC3T3-E1 cells (pre-osteoblasts) but reduced the TRAP+ RAW264.7 cells (pre-osteoclasts). Aß treatment upregulated TCF1 and OPG proteins in MC3T3-E1 cells. Aß treatment upregulated IκB-α but downregulated NFATc1protein in RAW264.7 cells. These effects were blocked by XAV-939 (a Wnt signaling antagonist), and then rescued by additional Wnt3a (a Wnt agonist). CONCLUSION: Aß treatment simultaneously promoted osteogenic differentiation via Wnt/ß-catenin signaling, and inhibited osteoclasts differentiation via the OPG/RANKL/RANK system, suggesting Aß is a positive regulator of osteoblast differentiation and bone formation.

Percutaneous Transforaminal Endoscopic Discectomy Versus Microendoscopic Discectomy for Lumbar Disc Herniation: Two-Year Results of a Randomized Controlled Trial.

STUDY DESIGN: A prospective randomized controlled study. OBJECTIVE: To clarify whether percutaneous transforaminal endoscopic discectomy (PTED) has better clinical outcomes and less surgical trauma compared with microendoscopic discectomy (MED). SUMMARY OF BACKGROUND DATA: Two kinds of minimally invasive spine surgeries, PTED and MED, are now widely used for the treatment of lumbar disc herniation (LDH). It is still a controversial issue to choose the proper surgical approach. METHODS: In this single-center, open-label, randomized controlled trial, patients were included if they had persistent signs and symptoms of radiculopathy with corresponding imaging-confirmed LDH, and were randomly allocated to PTED or MED group. The primary outcome was the score of Oswestry Disability Index (ODI) and the secondary outcomes included the score of Medical Outcomes Study 36-Item Short-Form Health Survey bodily pain and physical function scales, European Quality of Life-5 Dimensions, and Visual Analogue Scales for back pain and leg pain. RESULTS: A total of 250 participants were randomly assigned to two treatment groups, 241 of that received the specific surgical procedure. Two hundred twenty-two patients (92.1%) have completed the 2-year follow-up. Both the primary and secondary outcomes did not differ significantly between the two treatment groups at each prespecified follow-up time (P > 0.05). For PTED, the postoperative improvement of ODI score in the median herniation subgroup was less compared with paramedian subgroup. For MED, less improvement of ODI score was found in far-lateral herniation subgroup compared with paramedian subgroup. Total complication rate over the course of 2 year was 13.44% in PTED group and 15.57% in MED group (P = 0.639). Ten cases (8.40%) in PTED group and five cases (4.10%) in MED group suffered from residue/recurrence of herniation, for which reoperation was required. CONCLUSION: Over the 2-year follow-up period, PTED did not show superior clinical outcomes and did not appear to be safer procedure for patients with LDH compared with MED. PTED had inferior results for median disc herniation, whereas MED did not appear to be the best option for far-lateral disc herniation. LEVEL OF EVIDENCE: 2.

Tangeretin Inhibits Oxidative Stress and Inflammation via Upregulating Nrf-2 Signaling Pathway in Collagen-Induced Arthritic Rats.

BACKGROUND/AIMS: Tangeretin (TAN), a major phytochemical in tangerine peels and an important Chinese herb, has multiple biological properties, especially antioxidative and anti-inflammatory effects. However, the mechanisms remain unclear. Based on these findings, the aim of the present study was to assess the antioxidant and anti-inflammatory properties of TAN in bovine type II collagen-induced arthritis rats. METHODS: TAN (50 mg/kg) was given orally once daily for 14 days. The effects of treatment were evaluated by biochemical assay (articular elastase, myeloperoxidase, end products of lipid peroxidation [MDA], antioxidant enzyme, such as superoxide dismutase, catalase, glutathione), nitric oxide, and inflammatory cytokines (interleukin-1ß [IL-1ß], -IL-10, tumor necrosis factor-alpha [TNF-α], interferon-γ [IFN-γ], and prostaglandin E2 [PGE2]). The protective effects of TAN against rheumatoid arthritis (RA) were evident from the decrease in arthritis scoring. Furthermore, the Nrf-2 signaling pathway was assessed to illustrate the molecular mechanism. RESULTS: TAN had therapeutic effects on RA by decreasing the oxidative stress damage and regulating inflammatory cytokine expression, including suppression of the accumulation of MDA products, decreasing the IL-1ß, TNF-α, IFN-γ, and PGE2 levels, enhancing the IL-10 and the activity of antioxidant enzymes, which was through upregulating Nrf-2 signaling pathway. CONCLUSION: TAN might have potential as a therapeutic agent for the treatment of RA.

[Comparative study of microendoscope-assisted and conventional minimally invasive transforaminal lumbar interbody fusion for degenerative lumbar diseases].

OBJECTIVE: To analyze the medium and long-term effectiveness of microendoscope-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for lumbar degenerative diseases in comparison with conventional tubular retractor-assisted MIS-TLIF. METHODS: Between November 2008 and March 2013, 53 patients with single segment lumbar degenerative diseases were enrolled. According to the different working channel performed, 28 patients were treated by microendoscope-assisted MIS-TLIF (observation group), while the remaining cases received conventional tubular retractor-assisted MIS-TLIF via Wiltse approach (control group). Preoperative baseline data, including age, gender, body mass index, disease etiology, operated level, the ration for requiring bilateral canal decompression, and preoperative visual analogue scale (VAS) socre of low back pain and leg pain, Japanese Orthopedic Association (JOA) score, Oswestry disability index (ODI) score, showed no significant difference between the two groups ( P>0.05). The operation time, intraoperative blood loss, intraoperative fluoroscopy time, postoperative analgesic drug dose, postoperation in-bed time, and perioperative complication incidence were recorded respectively and compared between the two groups. Radiographic evaluation of interbody fusion was performed based on Bridwell grading system at 2 years after operation. VAS scores of low back pain and leg pain, JOA score, and ODI score were assessed before operation, at 2 years after operation, and at last follow-up respectively. Surgical outcome satisfaction was assessed by modified MacNab criteria at last follow-up. RESULTS: When compared with those in control group, both intraoperative blood loss and postoperative analgesic drug dose were significantly decreased in observation group ( P<0.05); similarly, the operation time and intraoperative fluoroscopy time were also significantly increased in observation group ( P<0.05). There was no significant difference of postoperative in-bed time between the two groups ( t=-0.812, P=0.420). Both groups were followed up 6-10.3 years, with an average of 7.9 years. Regarding perioperative complication, its incidence was 14.3% and 20.0% in observation group and control group, respectively, showing no significant difference between both groups ( χ 2=0.306, P=0.580). Specifically, there were intraspinal hematoma formation in 1 case, incision infection in 1 case, urinary infection in 1 case, transient delirium in 1 case in observation group. By contrast, there were dural tear and cerebrospinal fluid leakage in 1 case, urinary infection in 1 case, pneumonia in 1 case, transient delirium in 2 cases in control group. Bridwell criterion was used to judge the intervertebral fusion at 2 years after operation, the fusion rates of observation group and control group were 92.9% and 92.0%, respectively, showing no significant difference ( χ 2=0.162, P=0.687). At both 2-year postoperatively and last follow-up, the VAS scores of low back pain and leg pain, JOA score, and ODI score were significantly improved when compared with those before operation ( P<0.01), whereas no significant difference between the two groups at either time point was found ( P>0.05). At last follow-up, the results of patients' satisfaction with surgery evaluated by modified MacNab criteria, and the excellent and good rates of the observation group and the control group were 96.4% and 92.0%, respectively, showing no significant difference ( χ 2=0.485, P=0.486). CONCLUSION: The medium and long-term effectiveness of microendoscope-assisted MIS-TLIF are similar to those of conventional tubular retractor-assisted MIS-TLIF for lumbar degenerative diseases. The former operation has the additional advantages in terms of more clear surgical site visually, less intraoperative blood loss, and reduced postoperative analgesic dose, all of which seem more feasible to clinical teaching.

Therapeutic Effects and Safety of Percutaneous Disc Decompression with Coblation Nucleoplasty in Cervical Vertigo: A Retrospective Outcome Study with 74 Consecutive Patients and Minimum 1-Year Follow-Up.

BACKGROUND: Surgical treatment of cervical vertigo has been rarely reported. This is the first retrospective study to evaluate the clinical outcomes of percutaneous disc decompression with coblation nucleoplasty (PDCN) for treatment of cervical vertigo. OBJECTIVES: To assess the clinical outcomes of patients with cervical vertigo who failed to improve with conservative care and who were subsequently treated with PDCN. STUDY DESIGN: This study used a retrospective design. SETTING: The research was conducted within an interventional vertigo management and spine practice. METHODS: Seventy-four consecutive patients with cervical vertigo underwent PDCN and were followed for at least one year. Outcome measures included the dizziness intensity Visual Analog Scale (VAS), dizziness frequency, the Dizziness Handicap Inventory (DHI), and neck pain intensity. Clinical efficacy was assessed by rating scale and the modified MacNab evaluation criteria. Surgical complications during the operation and follow-up were also recorded. RESULTS: The vertigo VAS score, frequency of dizziness, DHI, and neck pain intensity were all decreased significantly from evaluation before surgery to one week after surgery and to the last follow-up, giving a mean effective rate of 94.6% one week after surgery and 90.6% at the last follow-up. Good to excellent results were attained in 85.1% of these patients one week after PDCN and in 75.7% of the sufferers at the last follow-up (P < 0.001). There were 5 patients with transient adverse effects (6.25%) reported within the first month after surgery; they all recovered after conservative treatment. No neurological complications were found and no patient went on to spinal fusion surgery thereafter. LIMITATIONS: The rate of follow-up was 70% and a placebo effect cannot be excluded. There is no gold standard for the diagnosis and treatment of cervical vertigo so far. CONCLUSION: The clinical outcomes of PDCN for cervical vertigo were satisfactory in both the early and late postoperative period. PDCN is an effective, low-complication, minimally invasive procedure used to treat cervical vertigo. Further prospective randomized controlled trials are essential to verify this conclusion. KEY WORDS: Cervical vertigo, percutaneous disc decompression, coblation nucleoplasty, long-term outcome, dizziness intensity, dizziness frequency, dizziness handicap inventory, clinical efficacy, surgical complication, retrospective study.

Treatment of Single-Level Thoracic Tuberculosis by Percutaneous Endoscopic Débridement and Allograft via the Transforaminal Approach Combined with Percutaneous Pedicle Screw Fixation: A Multicenter Study with a Median Follow-Up of 36 Months.

OBJECTIVE: To examine effects of percutaneous endoscopic débridement and allograft via the transforaminal approach combined with percutaneous pedicle screw fixation as treatment for single-level thoracic tuberculosis. METHODS: This multicenter retrospective analysis included 75 patients with single-level thoracic tuberculosis who underwent percutaneous endoscopic débridement and allograft via the transforaminal approach combined with percutaneous pedicle screw fixation and were followed for >36 months between January 2012 and December 2014. RESULTS: Follow-up was 36-48 months (average 41.1 ± 2.2 months). Intraoperative blood loss was low (average 30.5 ± 7.9 mL), and bed rest time was short (average 1.5 ± 0.3 days). No recurrence was observed in all 75 patients. Except for 3 patients, almost all patients (96%) achieved grade I or II fusion in interbody bone grafting. Segmental Cobb angle was 13.5° ± 4.1° before surgery, 10.5° ± 3.7° immediately after surgery, and 11.7° ± 3.9° at 36 months of follow-up. All patients achieved complete recovery of neurologic function (American Spinal Injury Association grade E), including 15 patients with spinal cord injury (American Spinal Injury Association grade D) before surgery. The visual analog scale and 36-Item Short-Form Health Survey scores significantly improved at 1, 3, 12, and 36 months of follow-up. No complications related to internal fixation occurred within the follow-up period; complication rate was 9.0%. CONCLUSIONS: Median follow-up clinical experience with percutaneous endoscopic débridement and allograft via the transforaminal approach combined with percutaneous pedicle screw fixation indicates that the technique is safe, effective, feasible, and minimally invasive.

Downregulation of miR­505­3p predicts poor bone metastasis­free survival in prostate cancer.

The principal issue deriving from prostate cancer (PCa) is its propensity to metastasize to bone. To date, bone metastasis remains incurable, and therapeutic strategies are limited. Therefore, it is of paramount importance to explore predictive markers for bone metastasis of PCa. In the present study, we reported that miR­505­3p was significantly downregulated in bone metastatic PCa tissues compared with that in non­bone metastatic PCa tissues, but there was no significant difference in miR­505­3p expression between PCa and adjacent normal tissues. miR­505­3p expression was inversely associated with serum PSA levels, Gleason grade, N and M classification, and short bone metastasis­free survival in PCa patients, but had no effect on overall survival in PCa patients. Furthermore, upregulation of miR­505­3p suppressed the activity of TGF­ß signaling by directly targeting downstream effectors of TGF­ß signaling, SMAD2 and SMAD3, further inhibiting the invasion and migration abilities of PCa cells. Therefore, our findings unraveled a novel mechanism by which miR­505­3p inhibits bone metastasis of PCa, supporting the notion that miR­505­3p may serve as a predictive marker for bone metastasis of PCa.