Limin Rong

Unilateral pedicle screw fixation through a tubular retractor via the Wiltse approach compared with conventional bilateral pedicle screw fixation for single-segment degenerative lumbar instability: a prospective randomized study

OBJECT Treatment of patients with single-segment degenerative lumbar instability using unilateral pedicle screw fixation can achieve stability and fusion rates similar to those of bilateral pedicle screw fixation. The aim of this study was to analyze the clinical outcome of using unilateral pedicle screw fixation through a tubular retractor via the Wiltse approach to treat single-segment degenerative lumbar instability. METHODS Thirty-nine consecutive patients with single-segment, low-grade, degenerative lumbar instability were randomly assigned to treatment with either unilateral (n = 20) or bilateral (n = 19) pedicle screw fixation. In the unilateral group, patients underwent unilateral posterior lumbar interbody fusion (PLIF) and ipsilateral pedicle screw fixation through a tubular retractor via the Wiltse approach. In the bilateral group, patients underwent modified bilateral PLIF with bilateral pedicle screw fixation via the posterior midline approach. During follow-up, patients were evaluated using a visual analog scale (VAS), the Japanese Orthopaedic Association (JOA) score, and the Oswestry Disability Index. RESULTS The unilateral group had a shorter operative duration (p < 0.05) and less blood loss (p < 0.001). All patients completed more than 2 years of follow-up (mean 36 months). In general, the time trends in improvement on the VAS and JOA differed slightly between the groups through 2 years, but no significant difference in back pain VAS score or leg pain VAS score was found between these 2 groups at the 2-year follow-up. Complete bone fusion was shown on CT in all patients at the 2-year follow-up. CONCLUSIONS Unilateral pedicle screw fixation through a tubular retractor via the Wiltse approach appears to be as safe and effective as bilateral pedicle screw fixation for the treatment of single-segment degenerative lumbar instability.

Effects and mechanisms of melatonin on neural differentiation of induced pluripotent stem cells.

Melatonin, a lipophilic molecule mainly synthesized in the pineal gland, has properties of antioxidation, anti-inflammation, and antiapoptosis to improve neuroprotective functions. Here, we investigate effects and mechanisms of melatonin on neural differentiation of induced pluripotent stem cells (iPSCs). iPSCs were induced into neural stem cells (NSCs), then further differentiated into neurons in medium with or without melatonin, melatonin receptor antagonist (Luzindole) or Phosphatidylinositide 3 kinase (PI3K) inhibitor (LY294002). Melatonin significantly promoted the number of neurospheres and cell viability. In addition, Melatonin markedly up-regulated gene and protein expression of Nestin and MAP2. However, Luzindole or LY294002 attenuated these increase. The expression of pAKT/AKT were increased by Melatonin, while Luzindole or LY294002 declined these melatonin-induced increase. These results suggest that melatonin significantly increased neural differentiation of iPSCs via activating PI3K/AKT signaling pathway through melatonin receptor.

Comparison of anterior corpectomy and fusion versus laminoplasty for the treatment of cervical ossification of posterior longitudinal ligament: a meta-analysis.

OBJECTIVE The purpose of this study was to compare the effectiveness and safety of anterior corpectomy and fusion (ACF) with laminoplasty for the treatment of patients diagnosed with cervical ossification of the posterior longitudinal ligament (OPLL). METHODS The authors searched electronic databases for relevant studies that compared the use of ACF with laminoplasty for the treatment of patients with OPLL. Data extraction and quality assessment were conducted, and statistical software was used for data analysis. The random effects model was used if there was heterogeneity between studies; otherwise, the fixed effects model was used. RESULTS A total of 10 nonrandomized controlled studies involving 819 patients were included. Postoperative Japanese Orthopaedic Association (JOA) score (p = 0.02, 95% CI 0.30-2.81) was better in the ACF group than in the laminoplasty group. The recovery rate was superior in the ACF group for patients with an occupying ratio of OPLL of ≥ 60% (p < 0.00001, 95% CI 21.27-34.44) and for patients with kyphotic alignment (p < 0.00001, 95% CI 16.49-27.17). Data analysis also showed that the ACF group was associated with a higher incidence of complications (p = 0.02, 95% CI 1.08-2.59) and reoperations (p = 0.002, 95% CI 1.83-14.79), longer operation time (p = 0.01, 95% CI 17.72 -160.75), and more blood loss (p = 0.0004, 95% CI 42.22-148.45). CONCLUSIONS For patients with an occupying ratio ≥ 60% or with kyphotic cervical alignment, ACF appears to be the preferable treatment method. Nevertheless, laminoplasty seems to be effective and safe enough for patients with an occupying ratio < 60% or with adequate cervical lordosis. However, it must be emphasized that a surgical strategy should be made based on the individual patient. Further randomized controlled trials comparing the use of ACF with laminoplasty for the treatment of OPLL should be performed to make a more convincing conclusion.

Amyloid β Peptide Enhances RANKL-Induced Osteoclast Activation through NF-κB, ERK, and Calcium Oscillation Signaling

Osteoporosis and Alzheimer’s disease (AD) are common chronic degenerative disorders which are strongly associated with advanced age. We have previously demonstrated that amyloid beta peptide (Aβ), one of the pathological hallmarks of AD, accumulated abnormally in osteoporotic bone specimens in addition to having an activation effect on osteoclast (Bone 2014,61:164-75). However, the underlying molecular mechanisms remain unclear. Activation of NF-κB, extracellular signal-regulated kinase (ERK) phosphorylates, and calcium oscillation signaling pathways by receptor activator NF-κB ligand (RANKL) plays a pivotal role in osteoclast activation. Targeting this signaling to modulate osteoclast function has been a promising strategy for osteoclast-related diseases. In this study, we investigated the effects of Aβ on RANKL-induced osteoclast signaling pathways in vitro. In mouse bone marrow monocytes (BMMs), Aβ exerted no effect on RANKL-induced osteoclastogenesis but promoted osteoclastic bone resorption. In molecular levels, Aβ enhanced NF-κB activity and IκB-α degradation, activated ERK phosphorylation and stimulated calcium oscillation, thus leading to upregulation of NFAT-c1 expression during osteoclast activation. Taken together, our data demonstrate that Aβ enhances RANKL-induced osteoclast activation through IκB-α degradation, ERK phosphorylation, and calcium oscillation signaling pathways and that Aβ may be a promising agent in the treatment of osteoclast-related disease such as osteoporosis.

Proteins Reprogramming: Present and Future

Induced pluripotent stem cells (iPSCs) are of great clinical interest for they are derived from ones own somatic cells and have the potential of committed differentiation without immunological rejection after autografting. However, the use of viral and other modified vectors may still cause tumorigenesis due to chromosome insertion mutation, leading to limited practical use. iPSCs generated by reprogramming proteins overcome the potential safety risk and complicated manipulation procedures, thus they own better application prospective, yet some technical difficulties need to be studied and resolved, for instance, low reprogramming efficiency, unclear transduction, and reprogramming mechanism. In this paper, we summarize the current progress of proteins reprogramming technology for generation of iPSCs and discuss the promising efficiency-improved reprogramming methods by proteins plus other kinds of chemical compounds.

Interaction of iPSC-derived neural stem cells on poly(L-lactic acid) nanofibrous scaffolds for possible use in neural tissue engineering

Tissue engineering is a rapidly growing technological area for the regeneration and reconstruction of damage to the central nervous system. By combining seed cells with appropriate biomaterial scaffolds, tissue engineering has the ability to improve nerve regeneration and functional recovery. In the present study, mouse induced pluripotent stem cells (iPSCs) were generated from mouse embryonic fibroblasts (MEFs) with the non-integrating episomal vectors pCEP4-EO2S-ET2K and pCEP4-miR-302-367 cluster, and differentiated into neural stem cells (NSCs) as transplanting cells. Electrospinning was then used to fabricate randomly oriented poly(L-lactic acid) (PLLA) nanofibers and aligned PLLA nanofibers and assessed their cytocompatibility and neurite guidance effect with iPSC-derived NSCs (iNSCs). The results demonstrated that non-integrated iPSCs were effectively generated and differentiated into iNSCs. PLLA nanofiber scaffolds were able to promote the adhesion, growth, survival and proliferation of the iNSCs. Furthermore, compared with randomly oriented PLLA nanofibers, the aligned PLLA nanofibers greatly directed neurite outgrowth from the iNSCs and significantly promoted neurite growth along the nanofibrous alignment. Overall, these findings indicate the feasibility of using PLLA nanofiber scaffolds in combination with iNSCs in vitro and support their potential for use in nerve tissue engineering.

Percutaneous transforaminal endoscopic discectomy compared with microendoscopic discectomy for lumbar disc herniation: 1-year results of an ongoing randomized controlled trial

OBJECTIVE A prospective randomized controlled study was conducted to clarify whether percutaneous transforaminal endoscopic discectomy (PTED) results in better clinical outcomes and less surgical trauma than microendoscopic discectomy (MED). 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 lumbar disc herniation. Patients were randomly allocated to the PTED or the MED group by computer-generated randomization codes. The primary outcome was the Oswestry Disability Index (ODI) score 1 year after surgery. Secondary outcomes included scores of the Medical Outcomes Study 36-Item Short-Form Health Survey bodily pain and physical function scales, EuroQol Groups EQ-5D , and the visual analog scales for back pain and leg pain. Data including duration of operation, in-bed time, length of hospital stay, surgical cost and total hospital cost, complications, and reoperations were recorded. RESULTS A total of 153 participants were randomly assigned to 2 treatment groups (PTED vs MED), and 89.5% (137 patients) completed 1 year of follow-up. Primary and secondary outcomes did not differ significantly between the treatment groups at each prespecified follow-up point (p > 0.05). For PTED, there was less postoperative improvement in ODI score in the median herniation subgroup at 1 week (p = 0.027), 3 months (p = 0.013), 6 months (p = 0.027), and 1 year (p = 0.028) compared with the paramedian subgroup. For MED, there was significantly less improvement in ODI score at 3 months (p = 0.008), 6 months (p = 0.028), and 1 year (p = 0.028) in the far-lateral herniation subgroup compared with the paramedian subgroup. The total complication rate over the course of 1 year was 13.75% in the PTED group and 16.44% in the MED group (p = 0.642). Five patients (6.25%) in the PTED group and 3 patients (4.11%) in the MED group suffered from residue/recurrence of herniation, for which reoperation was required. CONCLUSIONS Over the 1-year follow-up period, PTED did not show superior clinical outcomes and did not seem to be a safer procedure for patients with lumbar disc herniation compared with MED. PTED had inferior results for median disc herniation, whereas MED did not seem to be the best treatment option for far-lateral disc herniation. Clinical trial registration no.: NCT01997086 (clinicaltrials.gov).

Effects and mechanisms of matrix metalloproteinase2 on neural differentiation of induced pluripotent stem cells

Induced pluripotent stem cells (iPSCs) possess the potential to differentiate into neural lineage cells. Matrix metalloproteinase 2 (MMP2), an endopeptidase in the extracellular matrix, has been shown to protect neural cells from injury. However, the mechanisms and effects of MMP2 on neural differentiation of iPSCs remain poorly understood. Here, we demonstrated a role for MMP2 in the differentiation of iPSCs to neurons via the AKT pathway. Treatment of iPSCs with MMP2 promoted their proliferation and differentiation into neural stem cells (NSCs), and then into neurons. The transcript and protein expression of Nestin and microtubule-associated protein 2 (MAP2) increased. Moreover, MMP2 markedly induced the expression of phospho-AKT (pAKT) during these differentiation stages. Consistently, silencing MMP2 using siRNA attenuated the expression of Nestin, MAP2 and pAKT, compared with the control group. In addition, the increasing levels of Nestin, MAP2 and pAKT in the MMP2 group were declined by pretreatment with the phosphoinositide 3-kinase (PI3K)/AKT inhibitor, LY294002. Furthermore, the study detected that TrkA and TrkB were perhaps the potential receptors for these effects of MMP2 on neural differentiation through PI3K/AKT signaling pathway. Taken together, these results suggest that MMP2 induces the differentiation of iPSCs into neurons by regulating the AKT signaling pathway.

Perineurium-like sheath derived from long-term surviving mesenchymal stem cells confers nerve protection to the injured spinal cord

The functional multipotency enables mesenchymal stem cells (MSCs) promising translational potentials in treating spinal cord injury (SCI). Yet the fate of MSCs grafted into the injured spinal cord has not been fully elucidated even in preclinical studies, rendering concerns of their safety and genuine efficacy. Here we used a rat spinal cord transection model to evaluate the cell fate of allograft bone marrow derived MSCs. With the application of immunosuppressant, donor cells, delivered by biocompatible scaffold, survived up to 8 weeks post-grafting. Discernible tubes formed by MSCs were observed beginning 2 weeks after transplantation and they dominated the morphological features of implanted MSCs at 8 weeks post-grafting. The results of immunocytochemistry and transmission electron microscopy displayed the formation of perineurium-like sheath by donor cells, which, in a manner comparable to the perineurium in peripheral nerve, enwrapped host myelins and axons. The MSC-derived perineurium-like sheath secreted a group of trophic factors and permissive extracellular matrix, and served as a physical and chemical barrier to insulate the inner nerve fibers from ambient oxidative insults by the secretion of soluble antioxidant, superoxide dismutase-3 (SOD3). As a result, many intact regenerating axons were preserved in the injury/graft site following the forming of perineurium-like sheath. A parallel study utilizing a good manufacturing practice (GMP) grade human umbilical cord-derived MSCs or allogenic MSCs in an acute contusive/compressive SCI model exhibited a similar perineurium-like sheath formed by surviving donor cells in rat spinal cord at 3 weeks post-grafting. The present study for the first time provides an unambiguous morphological evidence of perineurium-like sheath formed by transplanted MSCs and a novel therapeutic mechanism of MSCs in treating SCI.

A novel indication for a method in the treatment of lumbar tuberculosis through minimally invasive extreme lateral interbody fusion (XLIF) in combination with percutaneous pedicle screws fixation in an elderly patient: A case report

Rationale:To describe a novel indication for a method through minimally invasive extreme lateral interbody fusion (XLIF) in combination with percutaneous pedicle screwsfixation in the treatment of lumbar tuberculosis (TB) in an elderly patient, and its clinical efficacy and feasibility. Lumbar TB is a destructive form of TB. Antituberculous treatment should be started as early as possible. In some circumstances, however, surgical debridement with or without stabilization of the spine appears to be beneficial and may be recommended. Surgeries through the approach of anterior or posterior are still challenging and often involve some complications. Patient concerns:The case is a 68-year-old female who was misdiagnosed as simple vertebral compression fracture and underwent L1 and L2 percutaneous vertebroplasty in another hospital 7 years ago. He complained of lumbosacral pain for 1 month this time. Magnetic resonance imaging (MRI) and computed tomography (CT) showed intervertebral space in L1/2 was seriously damaged like TB. Diagnoses:Lumbar tuberculosis Interventions:Antitubercular drugs, mini-invasive debridement with XLIF in combination with percutaneous pedicle screwsfixation was performed. This patient was followed up for 12 months. Outcomes:No obvious complication occurred during the operation and the wound healed well. Oswestry Disability Index (ODI: 56 vs 22) and visual analog scale (VAS: 4 vs 0) score significantly decreased atfinal follow-up of 12 months. Obvious recovery of kyphosis angle was found postoperatively (post: 14.8° vs pre: 33.5°). No recurrent infection occurred at the last follow-up. Lessons:Mini-invasive surgery by debridement through XLIF and percutaneous pedicle screwsfixation may be an effective and innovative treatment method for lumbar TB in the elderly.