Isobavachalcone prevents osteoporosis by suppressing activation of ERK and NF-κB pathways and M1 polarization of macrophages.

Estrogen receptors alpha (ERα), a member of the nuclear receptor protein family, was found to play an important role in maintaining bone mass. Its downstream signaling proteins such as ERK and NF-κB were reported to be involved in development of osteoporosis, which meant that targeting ERα might be an effective strategy for searching for new drugs to prevent bone loss. In this study, we demonstrate that isobavachalcone (ISO), as one of bioactive compounds isolated from Psoralea corylifoliaLinn, has high affinity with ERα. The effects of ISO are investigated on receptor activator of NF-κB ligand (RANKL)-induced osteocalstogenesis. It is reported that ISO inhibits the RANKL-mediated increase of osteoclast-related genes MMP9, cathepsink and TRAR in RAW264.7 cells. Moreover, in vitro experiment shows that ISO exhibits an inhibitory effect on ERK and NF-κB signaling pathway, and suppresses RANKL-induced expression of osteoclast-related transcription factors NFATc1 and c-Fos. However, the impact of ISO in these molecules is eliminated by the application of ERα antagonist AZD9496.We further verified pharmacological effects of ISO in ovariectomized osteoporotic mice, and ISO significantly prevented bone loss and decreased M1 polarization of macrophages from marrow and spleen. Collectively, our data suggest that ISO prevents osteoporosis via suppressing activation of ERK and NF-κB signaling pathways as well as M1 polarization of macrophages.

Minimally invasive surgery for paravertebral or psoas abscess with spinal tuberculosis - a long-term retrospective study of 106 cases.

BACKGROUND: Minimally invasive surgery (MIS) is a common treatment option for paravertebral or psoas abscesses (PAs) in patients with spinal tuberculosis (ST). However, its efficacy remains controversial. The aim of the study was to evaluate the efficacy of MIS for PA with ST combined with anti-tuberculous chemotherapy. METHODS: A total of 106 consecutive patients who underwent MIS for ST with PA from January 2002 to Oct 2012 were reviewed. The MIS involved computed tomography (CT)-guided percutaneous catheter drainage and percutaneous catheter infusion chemotherapy. Clinical outcomes were evaluated based on the changes observed on preoperative and postoperative physical examination, inflammatory marker testing, and magnetic resonance imaging (MRI). RESULTS: The mean follow-up period was 7.21 ± 3.15 years. All surgeries were successfully completed under CT-guidance without intraoperative complications and all patients experienced immediate relief of their symptoms, which included fever and back pain. The preoperatively elevated erythrocyte sedimentation rate and C-reactive protein values returned to normal at a mean period of 3 months postoperatively. Solid bony union was observed in 106 patients and no abscesses were found on MRI examination. CONCLUSION: MIS carries advantages in terms of less invasiveness, precise drainage, and enhanced local drug concentration. While the technique has not been fully characterized and clinically prove, its use in addition to conservative chemotherapy and open debridement and instrumental fixation may be recommended for patients with ST and PA.

A twin­pair analysis indicates congenital scoliosis is associated with allele­specific methylation in the SVIL gene.

Congenital scoliosis (CS) is a congenital disease resulting in abnormal vertebral development. Several studies have indicated that both genetic and environmental factors during pregnancy increase the risk of CS development. However, the exact mechanisms underlying CS pathogenesis remain unknown. To address this issue, both genetic (by whole­exome sequencing) and epigenetic (by methylated DNA immunoprecipitation sequencing) maps from CS disease­discordant monozygotic twins were generated in the present study. The differences in the presence of common and rare single nucleotide polymorphisms and in methylation patterns between the twins were investigated. The results indicated that rare mutations were more likely to underlie CS development compared with common mutations. Furthermore, differences in the allele­specific methylation pattern in the supervillin (SVIL) gene between the twins were identified. It has been reported that SVIL exerts a number of functions associated with CS, indicating its role as a novel mechanism promoting CS pathogenesis.

Relationship between postoperative lordosis distribution index and adjacent segment disease following L4-S1 posterior lumbar interbody fusion.

BACKGROUND: Adjacent segment disease (ASD) is an acknowledged problem of posterior lumbar interbody fusion (PLIF). Many studies have been reported concerning the role of lordosis distribution index (LDI) in spinal biomechanics. However, few reports have been published about the impact of LDI on ASD following L4-S1 PLIF. METHODS: The study enrolled 200 subjects who underwent L4-S1 PLIF for degenerative spine disease from 2009 to 2014. The average follow-up term was 84 months. Several lower lumbar parameters were measured, including lower lumbar lordosis (LLL), lumbar lordosis (LL), pelvic incidence (PI), and LDI on the pre and postoperative radiograph. Perioperative information, comorbidities, and operative data were documented. Kaplan-Meier curves were plotted for the comparisons of ASD-free survival of 3 different types of postoperative LDI subgroups. RESULTS: The incidence of ASD was found to be 8.5%. LL and LLL increased by 3.96° (38.71° vs 42.67°; P < 0.001) and 3.60° (26.22° vs 28.82°; P < 0.001) after lower lumbar fusion surgery, respectively. Lordosis distribution index (LDI) increased by 0.03 (0.66 vs 0.69, P = 0.004) postoperatively. A significant difference (P = 0.001) was observed when comparing the incidence of ASD among postoperative LDI subgroups. The Kaplan-Meier curves showed a marked difference in ASD-free survival between low and moderate LDI subgroup (log-rank test, P = 0.0012) and high and moderate LDI subgroup (log-rank test, P = 0.0005). CONCLUSION: Patients with abnormal postoperative LDI were statistically more likely to develop ASD than those who had normal postoperative LDI. Moreover, patients with low postoperative LDI were at greater risk for developing ASD than those with high postoperative LDI over time.

Long Noncoding RNA SERTAD2-3 Inhibits Osteosarcoma Proliferation and Migration by Competitively Binding miR-29c.

Background: Osteosarcoma (OS) is a malignant tumor disease with high morbidity and mortality in children and adolescents. Recently, attention has been focused on the effects of long noncoding RNAs (lncRNAs) on tumor biology. In this study, we identified the role of lnc-SERTAD2-3 in the development of OS. Materials and Methods: Sixty OS samples and adjacent tissues were collected to determine the relationship between lnc-SERTAD2-3 levels and clinicopathological characteristics. Quantitative real-time PCR (qPCR) was used to measure gene expression levels. A transwell invasion assay, a Cell Counting Kit-8 assay, and flow cytometry were used to measure cell migration, growth, and apoptosis, respectively. The binding site between the lnc-SERTAD2-3 and miR-29c RNAs was evaluated using a luciferase reporter assay. Results: The expression of the lnc-SERTAD2-3 was significantly downregulated in OS samples and three OS cell lines (MG-63, U2OS, and Saos-2) compared to normal tissue. Patients with lower levels of lnc-SERTAD2-3 expression had a more unfavorable prognosis (larger OS size, distant metastasis, and recurrence). Overexpression of lnc-SERTAD2-3 inhibited proliferation and migration, and promoted apoptosis in OS cells. Moreover, we found that lnc-SERTAD2-3 could suppress miR-29c by direct binding. Moreover, reexpression of miR-29c reversed the effect of lnc-SERTAD2-3 on OS cells. Conclusion: Overall, lnc-SERTAD2-3, an OS suppressor, is involved in the inhibition of OS proliferation and migration by targeting miR-29c.

Comparison of loss of correction between PSO and VCD technique in treating thoracolumbar kyphosis secondary to ankylosing spondylitis, a minimum 2 years follow-up.

BACKGROUND: Pedicle subtraction osteotomy (PSO) and vertebral column decancellation (VCD) are frequently used methods for correction of thoracolumbar kyphosis resulting from ankylosing spondylitis (AS). However, there are limited reports performed to evaluate the difference of loss of correction and the effectiveness of PSO and VCD techniques in patients with thoracolumbar kyphosis secondary to AS. OBJECTIVE: To retrospectively estimate the effectiveness of correction and loss of correction of PSO and VCD techniques in patients with thoracolumbar kyphosis secondary to AS. METHODS: We performed a retrospective review of 61 consecutive AS kyphosis patients undergoing PSO or VCD surgery from March 2012 to April 2015. The patients were divided into PSO group (n = 25) and VCD group (n = 36) according to the types of osteotomies. Measurement of the radiographic parameters was performed and the change was analyzed. RESULTS: Mean loss of correction in the global kyphosis was 2.31° in the PSO group and 2.29° in VCD group at the last follow-up, respectively, with no significant difference. Progressive junctional kyphosis occurred in both groups. VCD obtained a significantly larger correction than PSO while sharing a similar incidence of complications. No serious complications were observed in the two groups. CONCLUSION: The PSO osteotomy and VCD osteotomy are both safe and effective methods in treating thoracolumbar kyphosis secondary to AS. Mild loss of correction mainly occurred in the global kyphosis in both techniques with no significant difference.

Long noncoding RNA PXN-AS1-L promotes non-small cell lung cancer progression via regulating PXN.

BACKGROUND: Increasingly evidences suggest that long noncoding RNAs (lncRNAs) play important roles in various cancers. LncRNA PXN-AS1-L is recently revealed to act as on oncogene in liver cancer. However, the expression, functions, and mechanisms of action of PXN-AS-L in non-small cell lung cancer (NSCLC) remain unclear. METHODS: The expression of PXN-AS1-L in primary NSCLC tissues, NSCLC bone metastasis tissues, and cell lines was measured by quantitative real-time PCR. The correlations between PXN-AS1-L expression and clinicopathological characteristics of NSCLC patients were analyzed by Pearson Chi square test and log-rank test. The roles of PXN-AS1-L in cell viability, proliferation, apoptosis, and migration of NSCLC cells, and in vivo NSCLC tumor growth were investigated by a series of gain-of-function and loss-of-function assays. The regulatory roles of PXN-AS1-L on PXN were determined by quantitative real-time PCR and western blot. RESULTS: PXN-AS1-L was up-regulated in NSCLC tissues compared with noncancerous lung tissues, and PXN-AS1-L was further up-regulated in NSCLC bone metastasis tissues. Increased expression of PXN-AS1-L was positively associated with advanced TNM stages and poor prognosis. Gain-of-function and loss-of-function assays showed that PXN-AS1-L increased cell viability, promoted cell proliferation, inhibited cell apoptosis, and promoted cell migration of NSCLC cells. Xenograft assays showed that PXN-AS1-L also promoted NSCLC tumor growth in vivo. Mechanistically, we found that PXN-AS1-L, as an antisense transcript of PXN, up-regulated the expression of PXN. PXN was also up-regulated in NSCLC tissues. The expression of PXN and PXN-AS1-L was positively correlated in NSCLC tissues. Furthermore, PXN knockdown attenuated the roles of PXN-AS1-L in increasing cell viability, promoting cell proliferation, inhibiting cell apoptosis, and promoting cell migration of NSCLC cells. CONCLUSIONS: Our data revealed that PXN-AS1-L is up-regulated and acts as an oncogene in NSCLC via up-regulating PXN. Our data suggested that PXN-AS1-L might serve as a potential prognostic biomarker and therapeutic target for NSCLC.

Ankylosing spondylitis kyphosis surgical correction postoperative evaluation via SRS-22 domain investigation.

BACKGROUND: The SRS-22 is used to evaluate clinical outcomes in ankylosing spondylitis kyphosis patients. This study aimed to investigate the relationship between Scoliosis Research Society-22 (SRS-22) domains and satisfaction with management in patients who underwent surgical correction for ankylosing spondylitis kyphosis. The relationship between patient satisfaction and SRS-22 domain scores will feedback abundant information of therapeutic effect and significance for treatment guidance. METHODS: In this work, 106 patients with ankylosing spondylitis kyphosis at a single institution, who underwent posterior spinal fusion of five levels or more to the sacrum, completed SRS-22 evaluation preoperatively and followed up for a minimum of 2-year postoperation. Wilcoxon tests were performed to compare preoperative with 2-year postoperative scores. Spearman correlations were investigated to evaluate associations between the 2-year treatment satisfaction and therapeutic effect in SRS-22 domain scores. RESULTS: There were 12 females and 94 males with mean BMI of 16.4 kg/m2 and at the mean age of 46.3 years. All of the primary surgeries were treatments performed with mean follow-up of 26 months. A statistical improvement between paired pre- and 2-year postoperative SRS-22 domain scores and most radiographical parameters, commonly P ≤ 0.05, was designed and implemented. The majority of patients gave SRS-22 satisfaction score with 3.0 or more (88.5%) or 4.0 or more (68.8%), which are consistent with the moderate ceiling effect. Spearman coefficient correlations between the SRS-22 domain scores and patient satisfaction were all statistically significant, and they were from low to strong: [Mental (0.30), Activity (0.71), Pain (0.25), and Appearance (0.40)]. Furthermore, correlations for all radiographical and operative parameters were from low to strong. CONCLUSION: SRS-22 Activity domain correlates strongest with patient satisfaction in ankylosing spondylitis kyphosis patients who have undergone surgical correction at 2-year follow-up.

Percutaneous endoscopic interlaminar discectomy of L5-S1 disc herniation: a comparison between intermittent endoscopy technique and full endoscopy technique.

BACKGROUND: Percutaneous endoscopic laminar discectomy is a typical minimally invasive discectomy operation that is classified into the percutaneous endoscopic transforaminal discectomy and the percutaneous endoscopic interlaminar discectomy. Based on whether the surgeon chooses to deal with the ligamentum flavum under endoscope guidance, percutaneous endoscopic discectomy by the interlaminar approach can be performed with a full endoscope technique with the intermittent endoscope technique. To our knowledge, there is no study comparing these two techniques in regard to their surgical effects and advantages. Therefore, we conducted this study to compare the cost, safety, and efficacy between the intermittent endoscopy technique and full endoscopy technique of endoscopic interlaminar lumbar discectomy at the L5-S1 level. METHODS: From September 2014 to March 2015, a total of 126 patients with radiculopathy due to L5-S1 disc herniation who were treated by a full endoscopy technique (65 patients) or intermittent endoscopy technique (61 patients) were included. Relevant data, such as duration time of the operation, hospitalization expenses, postoperative bed rest time, length of hospitalization, and complication rates, were recorded. Clinical outcomes were assessed by the visual analog scale score, modified MacNab criteria, and Oswestry disability index. RESULTS: In the full endoscope (FE) group, the mean duration time of surgery was 75.0 ± 11.9 min. The postoperative bed rest time was 6.5 ± 1.1 h, length of hospitalization was 3.8 ± 1.1 days, and complication rate was 7.69%. In the intermittent endoscopy (IE) group, the mean duration time of surgery was 43.0 ± 16.4 min. The postoperative bed rest time was 5.0 ± 1.1 h, length of hospitalization was 3.6 ± 1.2 days, and complication rate was 6.60%. The average hospitalization expenses of the FE group and IE group, respectively, were 32,069 ± 1086 RMB and 22,665 ± 899 RMB. There were significant differences in the surgical duration and hospitalization expenses (P < 0.01), but no differences between the two groups in postoperative bed rest time, length of hospitalization, or complication rates (P > 0.05). The postoperative Oswestry disability index and VAS were clearly improved in both groups compared with those of preoperation (P < 0.01). These two procedures have the same clinical outcomes (P > 0.05). CONCLUSIONS: Both the full endoscopy technique and intermittent endoscopy technique achieved good outcomes, whereas the intermittent endoscopy technique is a more effective option for a shorter duration surgery and lower hospitalization expenses.

Sciatic nerve repair using adhesive bonding and a modified conduit.

When repairing nerves with adhesives, most researchers place glue directly on the nerve stumps, but this method does not fix the nerve ends well and allows glue to easily invade the nerve ends. In this study, we established a rat model of completely transected sciatic nerve injury and repaired it using a modified 1 cm-length conduit with inner diameter of 1.5 mm. Each end of the cylindrical conduit contains a short linear channel, while the enclosed central tube protects the nerve ends well. Nerves were repaired with 2-octyl-cyanoacrylate and suture, which complement the function of the modified conduit. The results demonstrated that for the same conduit, the average operation time using the adhesive method was much shorter than with the suture method. No significant differences were found between the two groups in sciatic function index, motor evoked potential latency, motor evoked potential amplitude, muscular recovery rate, number of medullated nerve fibers, axon diameter, or medullary sheath thickness. Thus, the adhesive method for repairing nerves using a modified conduit is feasible and effective, and reduces the operation time while providing an equivalent repair effect.