Liangming Zhang

Amyloid beta peptide is elevated in osteoporotic bone tissues and enhances osteoclast function

PURPOSE Epidemiological studies show that patients with Alzheimers disease (AD) have an increased risk of developing osteoporotic hip fracture. However, whether abnormal amyloid beta peptide (Aβ) deposition, one of the pathological hallmarks of AD, also occurs in osteoporosis and the relationship between Aβ and human osteoporosis remain unknown. This study addressed these issues. METHODS Forty-five female patients (osteoporosis 21, osteopenia 16 and normal 8) with osteoporotic/traumatic vertebral compression fractures were enrolled and Aβ42 and amyloid precursor protein (APP) levels assessed in the biopsy specimens of vertebral trabecular bone using immunohistochemistry (IHC) staining and semi-quantitative evaluation assays. Spearman rank correlation analysis was applied to explore the association between Aβ42/APP levels and the corresponding bone mineral density (BMD). Moreover, immunofluorescent assays and laser scanning confocal microscopy assays were used to examine the expression patterns of Aβ42/APP in patient bone tissues and osteocytes. Additionally, eight female patients with osteoporotic/traumatic femoral neck fractures, including two control patients were selected and Aβ42 and APP were identified in the femoral necks by RT-PCR and Western blotting (WB) assays. Next, a rat model of ovariectomy-induced osteoporosis was created and we evaluated Aβ42 and APP expression differences in the proximal tibia by IHC and RT-PCR and WB assays in comparison with a sham-operation group. Finally, the RAW264.7 cell line and human bone marrow monocyte (hBMMC) derived osteoclasts and human Aβ42 co-culture assays were performed to investigate the effect of Aβ42 on osteoclasts cell viability, number, differentiation and activation by the Cell Counting Kit-8 assay, tartrate resistant acid phosphatase staining assay, RT-PCR assay measuring the lytic gene expression and hydroxyapatite resorption assay respectively. RESULTS The mRNA and protein expression levels of Aβ42 and APP were elevated remarkably in the osteoporotic bone tissues both from human and ovariectomized rats when compared with the age-/sex-matched controls. Moreover, the expression levels had a negative correlation with corresponding BMD in patients (RAβ42=-0.617, p<0.0001; RAPP=-0.531, p=0.0002). In addition, Aβ42 was located mainly in the membrane and cytoplasm of osteocytes and in the extracellular matrix, while APP was largely located in the membrane of the osteocytes. Finally, Aβ42 can potently enhance osteoclasts differentiation and activation but had no effect on osteoclasts cell viability or number (dose- and time-dependency did not exist and oligomerization of Aβ42 was not a prerequisite in the osteoclastogenesis assay). CONCLUSIONS Aβ is relevant to human osteoporosis and may have an important role in the pathogenesis of osteoporosis.

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.

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).

Microendoscopy-Assisted Minimally Invasive Versus Open Transforaminal Lumbar Interbody Fusion for Lumbar Degenerative Diseases: 5-Year Outcomes

OBJECTIVE We sought to evaluate 5-year outcomes between microendoscopy-assisted minimally invasive (MIS) and open transforaminal lumbar interbody fusion (TLIF). METHODS Sixty single-level MIS and open surgeries were performed (30 patients in either group). Perioperative parameters including operative duration, intraoperative estimated blood loss, fluoroscopy time, postoperative analgesic usage, ambulatory time, and complications were recorded. Visual analog scale (back and leg), Japanese Orthopaedics Association score, and Oswestry Disability Index were obtained. Finally, self-evaluation of surgical outcomes (modified MacNab criteria), interbody fusion rate (Bridwell grade 1), and prevalence of adjacent segment degeneration were assessed. RESULTS Intraoperative estimated blood loss and postoperative analgesia usage were reduced in the MIS group, and patients undergoing microendoscopy-assisted MIS-TLIF ambulated earlier than those receiving open TLIF postoperatively. Nevertheless, surgical duration and fluoroscopy time were prolonged in the MIS group. Complication incidences were similar in both groups. Visual analog scale (back and leg), Japanese Orthopaedics Association, and Oswestry Disability Index were improved at 1 month, 2 years, and 5 years postoperatively in both groups when compared with preoperative scores. Significant improvements in these scores were found in the MIS group at 1 month postoperatively, while at 2 years and 5 years postoperatively, both groups revealed comparable aforementioned scores. Excellent and perfect scale rating, interbody fusion rate, and adjacent segment degeneration prevalence between the groups were almost similar. CONCLUSIONS Microendoscopy-assisted MIS-TLIF is comparable with open TLIF in terms of 5-year outcomes with additional benefits of reduced intraoperative iatrogenic injury, decreased initial pain, minimized activity restrictions, and accelerated ambulation recovery after surgery.

Clinical and Radiographic Results of a Minimally Invasive Lateral Transpsoas Approach for Treatment of Septic Spondylodiscitis of the Thoracolumbar and Lumbar Spine

BACKGROUND The minimally invasive lateral transpsoas approach allows retroperitoneal access for discectomy and graft placement. However, the procedure has rarely been used for the treatment of septic spondylodiscitis. The purposes of this study were to evaluate the clinical and radiographic outcomes from this minimally invasive procedure for septic spondylodiscitis. METHODS Thirty-one consecutive patients (17 males and 14 females) were included in this study from July 2013 to January 2016. Clinical outcomes were assessed by Oswestry Disability Index, visual analog scale, modified Macnab criteria, and inflammatory parameters. Radiographic results were analyzed by studying the changes in diseased disc height, lordosis, and fusion status. RESULTS The Oswestry Disability Index and visual analog scale score improved by 58% and 69% at the last follow-up. The modified Macnab criteria were found to be excellent in 21 patients (68%) and good in 10 (32%). Inflammatory parameters normalized over the average 24 months follow-up. There were no major complications that might have influenced the outcomes in this cohort. A complete fusion after 12 months was achieved in 87% of patients. A mean 7.5 mm restoration in disc height and 6.4° restoration in lumbar lordosis were observed in all patients, whereas an average 4.5 mm loss in restored height resulting from graft subsidence was observed in 24 patients during the follow-up. However, graft subsidence did not influence clinical outcomes significantly. CONCLUSIONS A minimally invasive lateral transpsoas approach in combination with instrumentation provides a novel treatment for patients with septic spondylodiscitis without severe kyphosis and neurologic impairment.

Intraoperative Myelography in Transpsoas Lateral Lumbar Interbody Fusion for Degenerative Lumbar Spinal Stenosis: A Preliminary Prospective Study

Aim To investigate the feasibility and effectiveness of intraoperative myelography in determining adequacy of indirect spinal canal decompression during transpsoas lateral lumbar interbody fusion (LLIF). Methods Seven patients diagnosed with degenerative lumbar spinal stenosis (DLSS) were prospectively included to this study. All patients underwent LLIF and subsequently received intraoperative myelography to determine the effect of indirect spinal canal decompression, which was visualized in both anterior-posterior and lateral images. Those patients with insufficient indirect canal decompression were further resolved by microendoscopic canal decompression (MECD). Radiological parameters, including stenosis ratio and dural sac area of operated levels, were measured and compared before and after operation. Besides, all patients were followed up for at least one year using visual analogue scale (VAS) for back and leg, Japanese Orthopaedic Association score (JOA), and Oswestry disability index (ODI). Results Seven patients with 8 operated levels underwent LLIF safely and demonstrated significant symptom relief postoperatively. Five operated levels showed adequate indirect canal decompression intraoperatively, while the remaining three levels did not achieve the adequacy, and their residual stenosis was resolved following MECD. Radiological parameters were improved statistically when compared with preoperation (P < 0.05). Furthermore, neurological symptoms of all patients were also improved significantly (P < 0.05), shown by improved VAS (back and leg), JOA, and ODI at both two-week and one-year follow-up. Conclusions Intraoperative myelography during LLIF is able to assess adequacy of indirect canal decompression for DLSS, thus promising favorable clinical outcomes.

An effective and practical immunohistochemical protocol for bone specimens characterized by hyaluronidase and pepsin predigestion combined with alkaline phosphatase-mediated chromogenic detection

The aim of this study was to provide an effective procedure for immunohistochemistry (IHC) investigations of bone specimens. Samples from rat femoral and human vertebral bone were processed with a detailed and effective IHC protocol summarized here. First, a novel antigen retrieval (AR) method of hyaluronidase combined pepsin predigestion (H+P) was established and the optimal concentration and pH value for AR of bone specimens were determined. Second, the newly developed method was compared with existing AR methods (boiling in sodium citrate, hyaluronidase predigestion (H) and pepsin predigestion (P), with PBS only as the negative control) using two chromogenic detection systems (horseradish peroxidase (HRP) and alkaline phosphatase (AP)) to evaluate their efficacy in obtaining the best IHC results for bone samples. Considering the drawbacks of significant shrinking and detachment from slide for heat retrieval methods and the only moderate immunolabeling for H and P, H+P was the optimal AR method for IHC of bone specimens with the advantages of both good morphological preservation and strong immunoreactivity. Moreover, AP-mediated chromogenic detection was superior to HRP-labeled chromogenic detection due to significantly less non-specific staining. In conclusion, we presented an effective and practical IHC protocol for bone specimens characterized by H+P predigestion combined with AP-mediated chromogenic detection. Finally, a detailed troubleshooting guide was provided for common mistakes that occur during IHC processing of the bone tissue samples.