The acquisition of epithelial–mesenchymal transition (EMT) and/or existence of a sub-population of cancer stem-like cells (CSC) are associated with malignant behavior and chemoresistance. To identify which factor could promote EMT and CSC formation and uncover the mechanistic role of such factor is important for novel and targeted therapies. In the present study, we found that the long intergenic non-coding RNA linc-DYNC2H1-4 was upregulated in pancreatic cancer cell line BxPC-3-Gem with acquired gemcitabine resistance. Knockdown of linc-DYNC2H1-4 decreased the invasive behavior of BxPC-3-Gem cells while ectopic expression of linc-DYNC2H1-4 promoted the acquisition of EMT and stemness of the parental sensitive cells. Linc-DYNC2H1-4 upregulated ZEB1, the EMT key player, which led to upregulation and downregulation of its targets vimentin and E-cadherin respectively, as well as enhanced the expressions of CSC makers Lin28, Nanog, Sox2 and Oct4. Linc-DYNC2H1-4 is mainly located in the cytosol. Mechanically, it could sponge miR-145 that targets ZEB1, Lin28, Nanog, Sox2, Oct4 to restore these EMT and CSC-associated genes expressions. We proved that MMP3, the nearby gene of linc-DYNC2H1-4 in the sense strand, was also a target of miR-145. Downregulation of MMP3 by miR-145 was reverted by linc-DYNC2H1-4, indicating that competing with miR-145 is one of the mechanisms for linc-DYNC2H1-4 to regulate MMP3. In summary, our results explore the important role of linc-DYNC2H1-4 in the acquisition of EMT and CSC, and the impact it has on gemcitabine resistance in pancreatic cancer cells.

Treatment of spinal cord injury (SCI) remains challenging. Considering the rapid developments in neurorestorative therapies for SCI, we have revised and updated the Clinical Therapeutic Guidelines for Neurorestoration in Spinal Cord Injury (2016 Chinese version) of the Chinese Association of Neurorestoratology (Preparatory) and China Committee of International Association of Neurorestoratology. Treatment of SCI is a systematic multimodal process that aims to improve survival and restore neurological function. These guidelines cover real-world comprehensive neurorestorative management of acute, subacute, and chronic SCI and include assessment and diagnosis, pre-hospital first aid, treatment, rehabilitation, and complication management.

Background:This study evaluated the efficacy of percutaneous nucleoplasty using coblation technique for the treatment of chronic nonspecific low back pain (LBP), after 5 years of follow-up.Methods:From September 2004 to November 2006, 172 patients underwent percutaneous nucleoplasty for chronic LBP in our department. Forty-one of these patients were followed up for a mean period of 67 months. Nucleoplasty was performed at L3/4 in 1 patient; L4/5 in 25 patients; L5/S1 in 2 patients; L3/4 and L4/5 in 2 patients; L4/5 and L5/S1 in 7 patients; and L3/4, L4/5, and L5/S1 in 4 patients. Patients were assessed preoperatively and at 1 week, 1 year, 3 years, and 5 years postoperatively. Pain was graded using a 10-cm Visual Analogue Scale (VAS) and the percentage reduction in pain score was calculated at each postoperative time point. The Oswestry Disability Index (ODI) was used to assess disability-related to lumbar spine degeneration, and patient satisfaction was assessed using the modified MacNab criteria.Results:There were significant differences among the preoperative, 1-week postoperative, and 3-year postoperative VAS and ODI scores, but not between the 3- and 5-year postoperative scores. There were no significant differences in age, sex, or preoperative symptoms between patients with effective and ineffective treatment, but there were significant differences in the number of levels treated, Pfirrmann grade of intervertebral disc degeneration, and provocative discography findings between these two groups. Excellent or good patient satisfaction was achieved in 87.9% of patients after 1 week, 72.4% after 1 year, 67.7% after 3 years, and 63.4% at the last follow-up.Conclusions:Although previously published short- and medium-term outcomes after percutaneous nucleoplasty appeared to be satisfactory, our long-term follow-up results show a significant decline in patient satisfaction over time. Percutaneous nucleoplasty is a safe and simple technique, with therapeutic effectiveness for the treatment of chronic LBP in selected patients. The technique is minimally invasive and can be used as part of a stepwise treatment plan for chronic LBP.

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BackgroundThis randomized controlled trial was carried out to (1) evaluate the effect of nucleoplasty with coblation on the PLA2 activity in the degenerative intervertebral disks of an animal model and (2) explore the possible therapeutic mechanism of coblation in addition to the current theory, which focuses on decreasing the intradiskal pressure in the treatment of intervertebral disk degeneration.MethodsThirty-six animal models of intervertebral disk degeneration were successfully established and then randomly divided into two groups: the coblation group (n = 18) and coblation control group (n = 18). Nucleoplasty using coblation was performed in the coblation group. L4–5 and L5–6 intervertebral disk samples were harvested and analyzed for PLA2 activity in different groups at different time points.ResultsThe PLA2 activity in the coblation control group was significantly higher than that in the control group (194.86 ± 11.80 and 80.68 ± 5.56, respectively; P < 0.01). There was a significant decrease in the PLA2 activity 1 week after coblation than at the real time after coblation (154.39 ± 7.99 and 184.98 ± 9.43, respectively; P < 0.001). The PLA2 activity at 1 month after coblation remained at a lower level than those at 1 week and at the real time after coblation (142.63 ± 10.72, 154.39 ± 7.99, and 184.98 ± 9.43, respectively), but there was no significant decrease in the PLA2 activity between 1 week and 1 month after coblation.ConclusionsCoblation appeared to effectively degrade the PLA2 activity in the degenerative intervertebral disks of this animal model. This represents a potential mechanism for the clinical use of coblation in the treatment of low back pain.