Novel long non-coding RNA AV310809 promotes TGF-ß1 induced epithelial-mesenchymal transition of human peritoneal mesothelial cells via activation of the Wnt2/ß-catenin signaling pathway.

Peritoneal fibrosis (PF) is a crucial cause of the loss of peritoneal function in patients with peritoneal dialysis. To better understand the underlying mechanism of PF, we selected AV310809, which is one of the most highly upregulated lncRNA in fibrotic peritoneal tissue, for functional analysis. We used co-expression analysis to explore the potential relationship between AV310809 and coding genes. qPCR, WB and IF were applied to evaluate the expression and localization of AV310809, epithelial markers and proteins involved in the Wnt2/ß-catenin signaling pathway. The interaction between AV310809 and ß-catenin was examined using an RNA pulldown assay. The expression level of AV310809 was upregulated in fibrotic peritoneum and TGF-ß1 induced EMT in HPMCs. Ectopic overexpression of AV310809 promoted EMT and activated the Wnt2/ß-catenin signaling pathway. Furthermore, we demonstrated that AV310809 could interact with ß-catenin and blocking ß-catenin inhibited the augmentation of EMT by AV310809. These findings indicated that AV310809 promoted TGF-ß1-induced EMT in HPMCs through the activation of the Wnt2/ß-catenin signaling pathway, possibly by targeting ß-catenin. We suggest that AV310809 may be a new therapeutic target for the management of peritoneal dialysis-associated PF.

A rare case of giant osteoblastoma of the sacrum.

BACKGROUND: An osteoblastoma is a rare benign bone tumor characterized by formation of osteoid tissue and primitive bone and occurs more often in men than in women. They are often secondary to an osteoid osteoma and can be located at any site on the skeleton. Lesions generally involve the posterior elements of the spine, such as the pedicle and the lamina. CASE PRESENTATION: This study reports the case of a 25-year-old female who suffered from an osteoblastoma of the right sacrum with repeated swelling and pain in the right lumbosacral region for approximately 6 months. Computed tomography (CT) and magnetic resonance imaging (MRI) of the pelvis revealed a segmented, expansive, multiseptate lesion. Resection with wide margins was performed and a huge cavity of approximately 15â€¯× 8â€¯× 4.4 cm in the right sacrum and pelvis was formed after complete curettage of the tumor. The pathological analysis of the resected tissue was consistent with a benign osteoblastoma. A follow-up was performed 2 years later and the patient was eventually relieved of the pain, the mobility of the right leg was improved and the CT scan demonstrated no evidence of recurrence. CONCLUSION: Osteoblastomas most commonly occur in the spine but rarely also in the sacrum. Large core needle biopsies play an important role in the diagnostics. Intralesional surgery can be performed for treatment of osteoblastomas.

MiR-200a negatively regulates TGF-ß1-induced epithelial-mesenchymal transition of peritoneal mesothelial cells by targeting ZEB1/2 expression.

Although epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells was recognized as the key process of peritoneal fibrosis, which is a major cause of peritoneal failure related to peritoneal dialysis (PD), mechanisms underlying these processes remain largely unknown. In this study, we found that miR-200a was significantly downregulated in peritoneal tissues with fibrosis in a rat model of PD. In vitro, transforming growth factor (TGF)-ß1-induced EMT, identified by de novo expression of α-smooth muscle actin and a loss of E-cadherin in human peritoneal mesothelial cells (HPMCs), was associated with downregulation of miR-200a but upregulation of zinc finger E-box-binding homeobox 1/2 (ZEB1/2), suggesting a close link between miR-200a and ZEB1/2 in TGF-ß1-induced EMT. It was further demonstrated that miR-200a was able to bind to the 3'UTR of ZEB1/2, and overexpression of miR-200a blocked TGF-ß1-induced upregulation of ZEB1/2 and, therefore, inhibited EMT and collagen expression. In contrast, overexpression ZEB1/2 blocked miR-200a inhibition of EMT and collagen expression in HMPCs. In conclusion, miR-200a could negatively regulate TGF-ß1-induced EMT by targeting ZEB1/2 in peritoneal mesothelial cells. Blockade of EMT in HPMCS indicates the therapeutic potential of miR-200a as a treatment for peritoneal fibrosis associated with PD.

Expression of adiponectin in the subchondral bone of lumbar facet joints with different degrees of degeneration.

BACKGROUND: Osteoarthritis research has been most commonly performed in the setting of the articular cartilage of the knee. To the best of our knowledge, no studies have evaluated the role of adiponectin in osteoarthritis of the lumbar facet joint (FJOA). Therefore, in this study, we explored whether adiponectin was expressed in the lumbar facet joints and evaluated the role of adiponectin in FJOA. METHODS: We enrolled patients who underwent lumbar computed tomography (CT) and magnetic resonance imaging (MRI) at the Orthopedic Department of the First Affiliated Hospital of Nanchang from May 2015 to June 2016. Lumbar facet joints were obtained from 135 patients at the time of lumbar fusion surgery and divided into three groups according to the Weishaupt grade. Cytokine levels in the subchondral bones were evaluated by enzyme-linked immunosorbent assays (ELISAs), and adiponectin levels were determined by immunohistochemistry, western blotting, and quantitative polymerase chain reaction (qPCR). RESULTS: By ELISA, adiponectin levels were examined in the subchondral bone for lumbar facet joint, and adiponectin was found to be negatively correlated with BMI in 52 patients (p < 0.001, r = -0.861). By immunohistochemistry analysis, adiponectin was found to be expressed in the subchondral bone of the lumbar facet, whereas the cartilage area was negative for adiponectin expression. Immunostaining intensity and area was related to the degeneration of the lumbar facet joint, and, in our research, considerably decreased staining intensity and area were observed in more severely degenerated lumbar facet joints. Furthermore, the expression of adiponectin was also reduced in degenerated lumbar facet joints, and the level of decline corresponded to degeneration detected by western blotting and qPCR analysis (n = 27, p < 0.0001). CONCLUSIONS: Adiponectin expression was observed in the subchondral bone of the lumbar facet joint and decreased as the degree of degeneration increased. Thus, the results of this study provide new insights into the relationship between adiponectin and osteoarthritis.

Diagnosis and treatment of nonadjacent cryptococcal infections at the L1 and S1 vertebrae.

Cryptococcal spine infections are rare infections that are easy to misdiagnose and difficult to cure. Therefore, we report the case of a 25-year-old man who presented with nonspecific spinal lesions at L1 and S1. The patient underwent surgical removal of the lesions, and specimens were submitted for microbial identification, which identified a cryptococcal infection that was susceptible to amphotericin B. The patient exhibited marked improvement after receiving intravenous amphotericin B and remained asymptomatic (no back pain, fever, or other symptoms) at the 3­ and 9­month follow-ups. Similar cases of cryptococcal spine infections are rare, and we believe that our diagnostic findings and treatment experience may help improve the management of this rare disease.

Targeting ONECUT3 blocks glycolytic metabolism and potentiates anti-PD-1 therapy in pancreatic cancer.

BACKGROUND: Reprogramming glucose metabolism, also known as the Warburg effect (aerobic glycolysis), is a hallmark of cancers. Increased tumor glycolysis not only favors rapid cancer cell proliferation but reprograms the immune microenvironment to enable tumor progression. The transcriptional factor ONECUT3 plays key roles in the development of the liver and pancreas, however, limited is known about its oncogenic roles, particularly metabolic reprogramming. METHODS: Immunohistochemistry and Western blotting are applied to determine the expression pattern of ONECUT3 and its clinical relevance in pancreatic ductal adenocarcinoma (PDAC). Knockdown and overexpression strategies are employed to determine the in vitro and in vivo functions of ONECUT3. Chromatin immunoprecipitation, luciferase reporter assay, and gene set enrichment analysis are used to decipher the molecular mechanisms. RESULTS: The glycolytic metabolism is inversely associated with T-cell infiltration in PDAC. ONECUT3 is identified as a key regulator for PDAC glycolysis and CD8+ T-cell infiltration. Genetic silencing of ONECUT3 inhibits cell proliferation, promotes cell apoptosis, and reduces glycolytic metabolism as evidenced by glucose uptake, lactate production, and extracellular acidification rate. Opposite effects of ONECUT3 are observed in overexpression studies. ONECUT3 enhances aerobic glycolysis via transcriptional regulation of PDK1. Targeting ONECUT3 effectively suppresses tumor growth, increases CD8+ T-cell infiltration, and potentiates anti-PD-1 therapy in PDAC. Pharmacological inhibition of PDK1 also shows a synergistic effect with anti-PD-1 therapy. In clinical setting, ONECUT3 is closely associated with PDK1 expression and T-cell infiltration in PDAC and acts as an independent prognostic factor. CONCLUSIONS: Our study reveals a previous unprecedented regulatory role of ONECUT3 in PDAC glycolysis and provides in vivo evidence that increased glycolysis is linked to an immunosuppressive microenvironment. Moreover, targeting ONECUT3-PDK1 axis may serve as a promising therapeutic approach for the treatment of PDAC.

Retrospective analysis of drug resistance characteristics and infection related risk factors of multidrug-resistant organisms (MDROs) isolated from the orthopedics department of a tertiary hospital.

Patients infected with multidrug-resistant organisms (MDROs) are known to exhibit longer hospital stays and a significantly poorer prognosis. We performed a 6-year retrospective analysis of nosocomial infections reported in the orthopedics department of our institution, to gain valuable insights into antibiotic sensitivity and infectious characteristics of MDROs, in order to deduce effective measures to control the occurrence of multidrug-resistant infections in clinical practice. A retrospective, single center surveillance study (January 2012-December 2017) was performed on the nosocomial infections recorded in the department of orthopedics. A nosocomial infection is defined as one that develops when a patient is residing in a hospital but was not present at the time of admission. All relevant data, including basic patient information, cultivated bacterial strains, and antimicrobial resistance, was obtained from the hospital information system. A total of 1392 strains of pathogenic bacteria were isolated; 358 belonged to MDROs (detection rate = 25.7%). All the isolated strains of MDROs were mostly from secretions (52.2%). The number of cases infected with MDROs were 144 (40.2%) and 129 (36.0%) in the trauma and spinal wards, respectively. MRSA showed high resistance to ß lactam antibiotics, but was sensitive to quinolone antibiotics, linezolid and cotrimoxazole. ESBL-positive strains showed more sensitivity to carbapenem antibiotics (resistance rate < 10%). MDR nonfermenters showed high resistance to most antibiotics. Logistic multivariate analysis revealed age, open injury, and central nervous system injury as independent risk factors for multidrug resistant infections. A high antibiotic resistance rate and an increasing prevalence of infections with MDROs was identified in the orthopedics department. Patients with open injury, central nervous system injury and those aged ≥ 60 years, were more prone to multidrug-resistant infections. Clinicians should pay more attention to such patients in order to actively prevent and control the occurrence of infections caused by MDROs.

Composite Interventions on Outcomes of Severely and Critically Ill Patients with COVID-19 in Shanghai, China.

Background: The sixty-day effects of initial composite interventions for the treatment of severely and critically ill patients with COVID-19 are not fully assessed. Methods: Using a Bayesian piecewise exponential model, we analyzed the 60-day mortality, health-related quality of life (HRQoL), and disability in 1082 severely and critically ill patients with COVID-19 between 8 December 2022 and 9 February 2023 in Shanghai, China. The final 60-day follow-up was completed on 10 April 2023. Results: Among 1082 patients (mean age, 78.0 years, 421 [38.9%] women), 139 patients (12.9%) died within 60 days. Azvudine had a 99.8% probability of improving 2-month survival (adjusted HR, 0.44 [95% credible interval, 0.24-0.79]), and Paxlovid had a 91.9% probability of improving 2-month survival (adjusted HR, 0.71 [95% credible interval, 0.44-1.14]) compared with the control. IL-6 receptor antagonist, baricitinib and a-thymosin each had a high probability of benefit (99.5%, 99.4%, and 97.5%, respectively) compared to their controls, while the probability of trail-defined statistical futility (HR > 0.83) was high for therapeutic anticoagulation (99.8%; HR, 1.64 [95% CrI, 1.06-2.50]) and glucocorticoid (91.4%; HR, 1.20 [95% CrI, 0.71-2.16]). Paxlovid, Azvudine, and therapeutic anticoagulation showed a significant reduction in disability (p < 0.05) Conclusions: Among severely and critically ill patients with COVID-19 who received 1 or more therapeutic interventions, treatment with Azvudine had a high probability of improved 60-day mortality compared with the control, indicating its potential in a resource-limited scenario. Treatment with an IL-6 receptor antagonist, baricitinib, and a-thymosin also had high probabilities of benefit in improving 2-month survival, among which a-thymosin could improve HRQoL. Treatment with Paxlovid, Azvudine, and therapeutic anticoagulation could significantly reduce disability at day 60.

Secoisolariciresinol diglucoside Ameliorates Osteoarthritis via Nuclear factor-erythroid 2-related factor-2/ nuclear factor kappa B Pathway: In vitro and in vivo experiments.

Osteoarthritis (OA) is an age-related joint disease in which inflammation and extracellular matrix (ECM) degradation play a crucial role in the destruction of articular cartilage. Secoisolariciresinol diglucoside (SDG), the main lignan in wholegrain flaxseed, which has been reported to remarkably suppress inflammation and oxidative stress, may have potential therapeutic value in OA. In this study, the effect and mechanism of SDG against cartilage degeneration were verified in the destabilization of the medial meniscus (DMM) and collagen-induced (CIA) arthritis models and interleukin-1ß (IL-1ß)-stimulated osteoarthritis chondrocyte models. From our experiments, SDG treatment downregulated the expression of pro-inflammatory factors induced by IL-1ß in vitro, including inducible nitric oxide synthase (INOS), cyclooxygenase-2 (COX2), tumor necrosis factor (TNF-α), and interleukin 6 (IL-6). Additionally, SDG promoted the expression of collagen II (COL2A1) and SRY-related high-mobility-group-box gene 9(SOX9), while suppressing the expression of a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5) and matrix metalloproteinases 13(MMP13), which leads to catabolism. Consistently, in vivo, SDG has been identified to have chondroprotective effects in DMM-induced and collagen-induced arthritis models. Mechanistically, SDG exerted its anti-inflammation and anti-ECM degradation effects by activating the Nrf2/HO-1 pathway and inhibiting the nuclear factor kappa B (NF-κB) pathway. In conclusion, SDG ameliorates the progression of OA via the Nrf2/NF-κB pathway, which indicates that SDG may have therapeutic potential for OA.

Evaluation of bone mineral density in adolescent idiopathic scoliosis using a three-dimensional finite element model: a retrospective study.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is often accompanied by osteopenia and osteoporosis, which can cause serious complications. The aim of this study was to determine the specific bone mineral density (BMD) of each vertebral body in patients with AIS using biomechanical finite element modeling based on three-dimensional (3D) reconstruction. METHODS: This retrospective study involved 56 patients with AIS. Computed tomography (CT) and radiography were performed. Spinal vertebrae were segmented from the spinal CT images of patients with AIS to reconstruct 3D vertebral models. The vertebral models were meshed into tetrahedral finite elements to assess the BMD. RESULTS: The mean main curve Cobb angle was 88.6 ± 36.7°, and the mean kyphosis angle was 36.8 ± 31.5°. The mean BMD of the global spine was 0.83 ± 0.15 g/cm2. The highest BMD was measured on the concave side of the apex (0.98 ± 0.16 g/cm2). Apical vertebral BMD was negatively correlated with age and height (r = - 0.490, p = 0.009 and r = - 0.478, p = 0.043, respectively). There were no significant differences in BMD values between the concave and convex sides (p > 0.05). CONCLUSIONS: The 3D finite element modeling of BMD in patients with AIS is a reliable and accurate BMD measurement method. Using this method, the overall BMD of patients with AIS was shown to gradually decrease from the top to the bottom of the spine. Our findings provide valuable insights for surgical planning, choice of screw trajectories, and additional biomechanical analyzes using finite element models in the context of scoliosis.

Fuzzy Adaptive Switching Control for Stochastic Systems With Finite-Time Prescribed Performance.

The issue of fuzzy adaptive switching control for stochastic systems with arbitrary switching signal and finite-time prescribed performance is investigated in this article. A piecewise function is adopted to characterize finite-time prescribed performance, and the error signal is converted to a new state variable via the tangent function. Unknown functions are approximated via fuzzy-logic systems (FLSs). Based on the stochastic stability theory and common Lyapunov function, a fuzzy adaptive switching control scheme is presented. The control law is proposed for the stochastic switched closed-loop system so that not only all the signals are ensured to be semiglobally uniformly ultimately bounded (SGUUB) in probability but also a residual error related to the finite-time prescribed performance bound is guaranteed. Eventually, simulation studies for a practical system are given to show the effectiveness of the presented fuzzy adaptive switching control scheme.

Overexpression of hsa_circ_0006470 inhibits the malignant behavior of gastric cancer cells via regulation of miR-1234/TP53I11 axis.

Gastric cancer (GC) is a subtype of a common malignant tumor found in the digestive system. Hsa_circ_0006470 is known to be closely associated with the development of GC. Nevertheless, the mechanism by which hsa_circ_0006470 regulates the tumorigenesis of GC has not been fully elucidated. To investigate the role of hsa_circ_0006470 in GC, its expression levels were assessed in GES-1, AGS, MKN45, and SNU5 cells by reverse transcription-quantitative PCR. Fluorescence in situ hybridization was used to evaluate the localization of hsa_circ_0006470 in AGS and MKN45 cells. In addition, cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were performed to evaluate the viability and proliferation of GC cells, respectively. The dual-luciferase reporter assay was used to explore the interaction among hsa_circ_0006470, microRNA (miR)-1234, and TP53I11. The expression levels of TP53I11, Akt, p-Akt, forkhead box O1, and cyclin dependent kinase 2 in AGS cells were analyzed by Western blotting. The data indicated that hsa_circ_0006470 expression was downregulated in AGS cells. In addition, overexpression (OE) of hsa_circ_0006470 could inhibit the viability and proliferation of GC cells. Moreover, OE of hsa_circ_0006470 inhibited the migration of GC cells and induced G1 cell cycle phase arrest. Moreover, miR-1234 was bound to hsa_circ_0006470 and TP53I11 was targeted by miR-1234. Furthermore, OE of hsa_circ_0006470 inhibited the tumorigenesis of GC via the regulation of the miR-1234/TP53I11 axis. In summary, the present study demonstrated that OE of hsa_circ_0006470 notably inhibited the tumorigenesis of GC by regulating the miR-1234/TP53I11 axis. Therefore, the present study may provide a theoretical basis for exploring novel therapeutic strategies for the treatment of GC.

Epidemiologic Correlation and Drug Resistance Analysis of Pathogenic Bacteria in Different Open Limb Injury External Conditions.

OBJECTIVE: To study the epidemiological correlation and drug resistance of external factors of infection caused by open injury of limbs to pathogens. METHODS: This experiment is a retrospective study. We took the geographical location and climate of Nanchang, Jiangxi Province, China as the background, analyzed 2017 strains of pathogens from 1589 patients with limb trauma infection in a University Affiliated Hospital from 2012 to 2017. Patients were divided into three groups according to the type of incision: I, In-hospital infection of clean limb incision, II, In-hospital infection with open injury, III, Community infection with open injury of the limb. Groups II and Groups III were divided into six subgroups according to the causes of trauma, including: accidents from non-motor vehicles, machinery, cutting/piercing, pedestrian injuries, struck by/against, pedal cycles, and other injuries. We found eight common pathogens of orthopedic infection, which were mainly divided into Gram-positive bacteria (G+, mainly including Staphylococcus) and Gram-negative bacteria (G-, mainly Enterobacteriaceae). The relationship between main pathogens and damage mechanism, apparent temperature and relative humidity was discussed in this study. SPSS v22.0 was used for statistical analysis of the data. Friedman's two-way ANOVA was used to analyze the difference between the injury mechanism and incidence of pathogenic bacteria. Linear regression was used to determine the trend between the incidence of major pathogens and seasonal temperature and humidity. The level of significance was set as P < 0.05. RESULTS: There was no significant difference in the distribution of pathogens between Groups II and Groups III (P>0.05). The drug resistance of Groups III was significantly higher than that of Groups II and Groups I. G+ bacteria were resistant to cephalosporin, ceftriaxone and other cephalosporins and erythromycin and other macrolides. They were sensitive to vancomycin and linezolid. G- were resistant to the first- and the second-generation cephalosporins, including cefotetan and cefazolin, and ampicillin and other penicillins, while they were sensitive to third-generation cephalosporins, such as ceftazidime, as well as to levofloxacin and other quinolones, meropenem, and other beta-lactamases. The correlation between the injury mechanism and infection of pathogenic bacteria was not significant. The monthly average apparent temperature and relative humidity were correlated with the infection rate of pathogenic bacteria. CONCLUSION: In open injury of extremities, apparent temperature and relative humidity is an important risk factor for infection by pathogenic bacteria and the drug resistance of pathogenic bacteria in out-of-hospital infection was lower than that of hospital infection.

Influence of structural and material property uncertainties on biomechanics of intervertebral discs - Implications for disc tissue engineering.

This study investigated how variations of structural and material properties of human intervertebral discs (IVDs) affect the biomechanical responses of the IVDs under simulated physiological loading conditions using a stochastic finite element (SFE) model. An SFE method, which combined an anatomic FE model of human lumbar L3-4 segment and probabilistic analysis of its structural and material properties, was used to generate a dataset of 500 random disc samples with varying structural and material properties. The sensitivity of the biomechanical responses, including intervertebral displacements/rotations, intradiscal pressures (IDP), fiber stresses and matrix strains of annulus fibrosus (AF), were systematically quantified under various physiological loading conditions, including a 500N compression and 7.5Nm moments in the 3 primary rotations. Significant variations of the IDPs, IVD displacements/rotations, and stress/strain distributions were found using the dataset of 500 ramdom disc samples. Under all the loading conditions, the IDPs were positively correlated with the Poisson's ratio of the NP (r = 0.46 to 0.75, p = 0.004-0.001) and negatively with the Young's modulus of the annulus matrix (r = -0.48 to -0.65, p = 0.003-0.001). The primary intervertebral rotations were significantly affected by the Young's modulus of the annulus matrix (r = -0.44 to -0.71, p = 0.001-0.032) and the orientations of the annular fibers (r = -0.45 to -0.69, p = 0.001-0.029). The heterogeneity of structures and material properties of the IVD had distinct effects on the biomechanical performances of the IVD. These data could help improve our understanding of the intrinsic biomechanics of the IVD and provide references for optimal design of tissue engineered discs by controlling structural and material properties of the disc components.

Investigation of Alterations in the Lumbar Disc Biomechanics at the Adjacent Segments After Spinal Fusion Using a Combined In Vivo and In Silico Approach.

The development of adjacent segment degeneration (ASD) is a major concern after lumbar spinal fusion surgery, but the causative mechanisms remain unclear. This study used a combined in vivo and in silico method to investigate the changes of anatomical dimensions and biomechanical responses of the adjacent segment (L3-4) after spinal fusion (L4-S1) in five patients under weight-bearing upright standing conditions. The in vivo adjacent disc height changes before and after fusion were measured using a dual fluoroscopic imaging system (DFIS), and the measured in vivo intervertebral positions and orientations were used as displacement boundary conditions of the patient-specific three-dimensional (3D) finite element (FE) disc models to simulate the biomechanical responses of adjacent discs to fusion of the diseased segments. Our data (represented by medians and 95% confidence intervals) showed that a significant decrease by - 0.8 (- 1.2, - 0.4) mm (p < 0.05) in the adjacent disc heights occurred at the posterior region after fusion. The significant increases in disc tissue strains and stresses, 0.32 (0.21, 0.43) mm/mm (p < 0.05) and 1.70 (1.07, 3.60) MPa (p < 0.05), respectively, after fusion were found in the posterolateral portions of the outermost annular lamella. The intradiscal pressure of the adjacent disc was significantly increased by 0.29 (0.13, 0.47) MPa after fusion (p < 0.05). This study demonstrated that fusion could cause alterations in adjacent disc biomechanics, and the combined in vivo and in silico method could be a valuable tool for the quantitative assessment of ASD after fusion.

Prediction of biomechanical responses of human lumbar discs - a stochastic finite element model analysis.

BACKGROUND: Accurate biomechanical investigation of human intervertebral discs (IVDs) is difficult because of their complicated structural and material features. AIM: To investigate probabilistic distributions of the biomechanical responses of the IVD by considering varying nonlinear structural and material properties using a stochastic finite element (FE) model. METHODS: A FE model of a L3-4 disc was reconstructed, including the nucleus pulposus (NP), annular matrix and fibers. A Monte Carlo method was used to randomly generate 500 sets of the nonlinear material properties and fiber orientations of the disc that were implemented into the FE model. The FE model was analyzed under seven loading conditions: a 500 N compressive force, a 7.5Nm moment simulating flexion, extension, left-right lateral bending, and left-right axial rotation, respectively. The distributions of the ranges of motion (ROMs), intradiscal pressures (IDP), fiber stresses and matrix strains of the disc were analyzed. RESULTS: Under the compressive load, the displacement varied between 0.29 mm and 0.76 mm. Under the 7.5Nm moment, the ROMs varied between 3.0° and 6.0° in primary rotations. The IDPs varied within 0.3 MPa under all the loading conditions. The maximal fiber stress (3.22 ± 0.64 MPa) and matrix strain (0.27 ± 0.12%) were observed under the flexion and extension moments, respectively. CONCLUSION: The IVD biomechanics could be dramatically affected by the structural and material parameters used to construct the FE model. The stochastic FE model that includes the probabilistic distributions of the structural and material parameters provides a useful approach to analyze the statistical ranges of the biomechanical responses of the IVDs.

Long non-coding RNA HOTAIR/microRNA-761 sponge regulates PPME1 and further influences cell biological functions in thyroid carcinoma.

BACKGROUND: Most well-differentiated thyroid carcinomas display good therapeutic outcomes, but there are still some patients who are not sensitive to the general treatments lose their treatment opportunities. Thus, it is important to understand the molecular mechanisms that cause thyroid carcinoma, so as to find effective diagnostic and therapeutic targets. AIM OF THE STUDY: To explore the role of homeobox transcript antisense RNA (HOTAIR) in thyroid carcinoma through protein phosphatase methylesterase 1 (PPME1) by sponging microRNA 761 (miR-761). METHODS: The regulation network amongst HOTAIR, miR-761 and PPME1 was predicted by online sources. RT-PCR was conducted to evaluate the expression of HOTAIR and miR-761 in tumor tissues. Clinical data was collected and analyzed by Chi-square test. Cell apoptosis and proliferation was evaluated using three types of cancer cells (HTh-7, CAL-62, BCPAP) after treated with si-HOTAIR and miR-761inhibitor. The binding site among HOTAIR, miR-761 and PPME1 was verified by dual luciferase reporter assay. PPME1 expression was measured after HOTAIR and miR-761 were suppressed by western blot. Survival time was measured in nude mice using log-rank test. RESULTS: HOTAIR was expressed to a significantly greater extent than miR-761 in thyroid tumor tissues (P < .001). miR-761 and PPME1 were negatively correlated (coef = -1.91, P < .001). HOTAIR competitively binds to miR-761 and miR-761 directly targets PPME1. HOTAIR was highly correlated with TNM (χ 2 = 5.797, P = .016), tumor size (χ 2 = 7.955, P = .005) and lymphatic metastasis (χ 2 = 6.0, P = .014). HOTAIR promoted cell proliferation and inhibited cell apoptosis, whereas miR-761 did not. HOTAIR elevated and miR-761 suppressed PPME1 expression. HOTAIR expression appears to affect the survival time in vivo. CONCLUSION: HOTAIR regulated thyroid cancer cells by binding to miR-761 through PPME1.

Erratum: Beclin-1 knockdown decreases proliferation, invasion and migration of Ewing sarcoma SK-ES-1 cells via inhibition of MMP-9.

[This corrects the article DOI: 10.3892/ol.2017.7667.].

Investigation of in vivo three-dimensional changes of the spinal canal after corrective surgeries of the idiopathic scoliosis.

OBJECTIVE: To determine the three-dimensional (3D) changes of the spinal canal length (SCL) after corrective surgeries and their association with the radiographic and clinical outcomes of idiopathic scoliosis patients. The length of the spinal cord has been demonstrated to be strongly correlated with the SCL. Understanding the changes in SCL could help determine the morphologic changes in the spinal cord to prevent spinal cord injury. METHODS: Twenty-seven scoliotic patients' 3D spinal canal were investigated using computed tomography images. The SCL between the upper and lower end vertebrae (U/L-EV) was measured at five locations. The radiographic parameters of each patient and the patient-reported outcomes (PROs) scores were also collected. The correlations of the changes of the SCLs with the other factors were analyzed. RESULTS: The SCL between the U/L-EV changed non-uniformly at different locations. The post-operative SCLs were significantly elongated by 7.5 ± 3.5 mm (6.0 ± 2.5%, P < .001) at the concave side and compressed by -2.6 ± 2.6 mm (-1.9 ± 1.9%, P < .001) at the convex side. The elongations of the SCL at the concave and posterior locations were correlated with the radiographic parameters including the pre-operative main Cobb angles (r = .511, P = .006; r = .613, P = .001) and apical vertebral translation (AVT) (r = .481, P = .011; r = .684, P = .000). No PRO scores were found to correlate with the SCL changes. CONCLUSION: The corrective surgeries elongated the spinal canal mainly at the concave side and compressed at the convex side. The main thoracic Cobb angle, the changes of AVT, and Cobb angles were moderately associated with the changes of the SCLs, but no PRO score was found to associate with the changes of the SCLs. The data could be instrumental for the improvement of corrective surgeries that are aimed to maximize the correction of scoliosis and minimize the negative effect on the spinal cord to prevent neurological complications.

Ligament deformation patterns of the craniocervical junction during head axial rotation tracked by biplane fluoroscopes.

BACKGROUND: Frequently, treatment decisions for craniocervical injuries and instability are based on imaging findings, but in vivo ligament kinematics were poorly understood. This study was to determine in vivo deformation patterns of primary ligaments in the craniocervical junction (i.e., C0-2), including the cruciform ligament, alar ligaments, and accessory ligaments, during dynamic head axial rotation. METHODS: The skulls and cervical spines of eight asymptomatic female subjects were dynamically imaged using a biplane fluoroscopic imaging system, when they performed left and right head axial rotations. Using a 3D-to-2D registration technique, the in vivo positions and orientations of cervical segments were determined. An optimization algorithm was implemented to determine ligament wrapping paths, and the resulting ligament deformations were represented by percent elongations. Using paired t-tests, ligament deformations in the end-range position were compared to those in the neutral position. FINDINGS: No significant differences were observed in segmental motions during left and right head rotations (p > 0.05). In general, slight deformations occurred in each component of the cruciform ligament. For the alar ligaments, the ipsilateral ligament was lengthened from -0.7 ± 13.8% to 16.6 ± 15.7% (p < 0.001*). For the accessory ligaments, the contralateral ligament was lengthened from -2.9 ± 7.5% to 10.1 ± 6.2% (p < 0.001*). INTERPRETATION: This study reveals that there are distinct deformation patterns in craniocervical junction ligaments during dynamic axial head rotation. These ligament deformation data can enhance our understanding of the synergic function of craniocervical junction ligaments, and guide the treatment of craniocervical instability.