Tissue ultrasound imaging based on wavelet correlation analysis and pulse-inversion technique.

BACKGROUND: Pulse-inversion-based tissue harmonic imaging has been utilized for many years because it can effectively eliminate the harmonic leakage and produce low side-lobe. However, the pulse inversion method is sensitive to imaging object movements, which may result in motion artifacts. Spatial resolution and contrast were limited. OBJECTIVE: To improve ultrasound image quality by a new pulse-inversion-based tissue harmonic imaging technique. METHODS: Continuous wavelet transform is applied to investigate the correlation between mother wavelet and the received echoes from two opposite pulses. To get a better correlation, a novel mother wavelet named 'tissue wavelet' is designed based on the Khokhlov-Zabolotskaya- Kuznetsov (KZK) wave equation. Radio frequency data were obtained from open Ultrasonix SonixTouch imaging system. Experiments were carried on ultrasonic tissue phantom, human carotid artery and human liver. RESULTS: The average improvement of lateral spatial resolution is 49.52% compared to pulse-inversion-based tissue second-harmonic Imaging (PIHI). Contrast ratio (CR) and contrast-to-noise ratio (CNR) increased by 5.55 dB and 1.40 dB over PIHI. Tissue wavelet performs better than Mexh and Morl wavelet in lateral spatial resolution, CR, and CNR. CONCLUSION: The proposed technique effectively improves the imaging quality in lateral spatial resolution, CR, and CNR.

Biomechanical Evaluation of an Oblique Lateral Locking Plate System for Oblique Lumbar Interbody Fusion: A Finite Element Analysis.

OBJECTIVE: The oblique lateral locking plate system (OLLPS) is a novel internal fixation with a locking and reverse pedicle track screw configuration designed for oblique lumbar interbody fusion (OLIF). The OLLPS is placed in a single position through the oblique lateral surgical corridor to reduce operative time and complications associated with prolonged anesthesia and prone positioning. The purpose of this study was to verify the biomechanical effect of the OLLPS. METHODS: An intact finite element model of L1-S1 (intact) was established based on computed tomography images of a healthy male volunteer. The L4-L5 intervertebral space was selected as the surgical segment. The surgical models were established separately based on OLIF surgical procedures and different internal fixations: 1) stand-alone OLIF (SA); 2) OLIF with a 2-screw lateral plate; 3) OLIF with a 4-screw lateral plate; 4) OLIF with OLLPS; and 5) OLIF with bilateral pedicle screw fixation (BPS). After validation of the intact model, physiologic loads were applied to the superior surface of L1 to simulate motions such as flexion, extension, left bending, right bending, left rotation, and right rotation. The evaluation indices included the L4/5 range of motion, the L4 maximum displacement, and the maximum stresses of the superior and inferior end plates, the cage, and the supplemental fixation. RESULTS: During OLIF surgery, the OLLPS provided multiplanar stability similar to that provided by BPS. Compared with 2-screw lateral plate and 4-screw lateral plate, OLLPS had better biomechanical properties in terms of enhancing the instant stability of the surgical segment, reducing the stress on the superior and inferior end plates of the surgical segment, and decreasing the risk of cage subsidence. CONCLUSIONS: With a minimally invasive background, the OLLPS can be used as an alternative to BPS in OLIF and it has better prospects for clinical promotions and applications.

An experimental study on stress-shielding effects of locked compression plates in fixing intact dog femur.

BACKGROUND: In orthopedic application, stress-shielding effects of implant materials cause bone loss, which often induces porosis, delayed bone healing, and other complications. We aimed to compare the stress-shielding effects of locked compression plate (LCP) and limited-contact dynamic compression plate (LC-DCP) in dogs with plate-fixed femurs. METHODS: Bilateral intact femurs of 24 adult dogs were fixed by adult forearm 9-hole titanium plates using minimally invasive plate osteosynthesis (MIPPO) technology, with LCP on the left and LC-DCP on the right femurs. Dogs were sacrificed at 6 weeks, 12 weeks, and 24 weeks after surgery, and bone specimens were used to evaluate the efficacies of different fixing methods on bones through X-ray, dual-energy X-ray absorptiometry (DEXA), histology, MicroCT, and biomechanics analyses. RESULTS: X-ray results showed significant callus formation and periosteal reaction in the LC-DCP group. Bone cell morphology, degree of osteoporosis, and bone mineral density (BMD) changes of the LCP group were significantly better than that of the LC-DCP group. MicroCT results showed that the LCP group had significantly reduced degree of cortical bone osteoporosis than the LC-DCP group. Tissue mineral density (TMD) in the LCP group was higher than that in the LC-DCP group at different time points (6 weeks, 12 weeks, and 24 weeks). Biomechanics analyses demonstrated that the compressive strength and flexural strength of bones fixed by LCP were better than that by LC-DCP. CONCLUSIONS: Stress-shielding effects of LCP are significantly weaker than that of LC-DCP, which is beneficial to new bone formation and fracture healing, and LCP can be widely used in clinic for fracture fixation.

A randomized controlled trial with ≥5 years of follow-up comparing minimally invasive and open transforaminal lumbar interbody fusion in disc herniation at single level.

Minimally invasive transforaminal lumbar interbody fusion (m-TLIF) using transpedicular screws has various advantages over classical open (c-) TLIF. Up to date, comparative analyses of the TLIF procedures were following patients for <5 years. The objective of the present study was to compare the clinical effectiveness and complications of m- and c-TLIF in patients with single-level disc herniation with ≥5 years follow-up. Between June 2008 to July 2010, 91 patients with single-level lumbar degeneration were recruited and were randomly divided into two groups: m-TLIF and c-TLIF. The analyzed outcome measurements included: Surgery duration, intraoperative blood loss, X-ray exposure time, T2 relaxation time in magnetic resonance imaging (MRI), visual analogue scale (VAS) scores, Japanese orthopedic association (JOA) scores, fusion rate and complications during follow-up. No significant differences between m- and c-TLIF were observed with respect to surgery duration (P=0.077), volume of blood loss (P=0.115), complications and the need for an additional surgery (P=0.632). Significant differences between the groups were observed for X-ray exposure time (P<0.001) and MRI T2 relaxation times at 3 months post-surgery (P<0.001). At day 7 post surgery, recorded VAS and JOA scores were significantly improved in the m-TLIF compared with the c-TLIF group and non-significant differences between the groups were observed at >1 month follow-up. m-TLIF was a safe and effective tool in treating single-level lumbar disc herniation. However, careful attention to the surgical technique and precise anatomical knowledge were required. Further studies and refinement of the surgical techniques are necessary prior to treating multiple or more extensive lesions using the m-TLIF method.

The effect of temperature-control microwave on HELA and MG-63 cells.

CONTEXT: Hyperthermia has now been used to treat many kinds of solid malignancies. However, the applied thermal parameters about heat temperature and time varied all over the world, and no consensus about the optimal formula had been reached. Microwave ablation, as one of thermal ablation methods, is usually applied based on the fixed parameters of power and duration. As a result, too high temperature or overheating might not be avoided and excessive heating might cause some additional side effects to normal tissues. AIMS: To explore the optimal parameters of power and duration for the HELA and MG-63 cells in vitro. SETTINGS AND DESIGN: With a temperature-controlled microwave workstation, a microwave thermal ablation experiment was performed in vitro. SUBJECTS AND METHODS: The HELA and MG-63 cells were heated with 40°C, 45°C, 50°C, 55°C, and 60°C lasting for 5-30 min, respectively. Then, the cell viability was detected using four methods: Flow cytometer assay, nicotinamide adenine dinucleotide-diaphorase staining, Calcein-acetoxymethyl ester staining immediately after treatment, and CCK-8 assay 24 h later. RESULTS: The temperature-controlled microwave has an excellent ablation effect on both cell lines. Furthermore, when the thermal stimulation reached 55°C 25 min and 55°C 20 min for the HELA and MG-63 cells, respectively, or 60°C 5 min for both, all the viability indexes indicated immediately devitalization. CONCLUSION: It presented a preliminary minimum lethal dose of heat was validated on the cellular level in vitro, which should be verified and corrected further in vivo.

[Therapeutic effect and safety of montelukast sodium combined with budesonide in children with cough variant asthma: a Meta analysis].

OBJECTIVE: To evaluate the therapeutic effect and safety of montelukast sodium combined with budesonide in children with cough variant asthma. METHODS: The databases CNKI, Wanfang Data, VIP, PubMed, EMbase, and BioMed Central were searched for randomized controlled trials (RCTs) of montelukast sodium combined with budesonide in the treatment of children with cough variant asthma. Data extraction and quality assessment were performed for RCTs which met the inclusion criteria, and RevMan 5.3 software was used to perform quality assessment of the articles included and Meta analysis. RESULTS: A total of 11 RCTs involving 1 097 patients were included. The results of the Meta analysis showed that compared with the control group (inhalation of budesonide alone), the observation group (inhalation of montelukast sodium combined with budesonide) had significantly higher overall response rate and more improved pulmonary function parameters including forced expiratory volume in the first second, percentage of forced expiratory volume in the first second, and peak expiratory flow, as well as significantly lower recurrence rate (P<0.01). The incidence of adverse events showed no significant difference between the two groups. CONCLUSIONS: Inhalation of montelukast sodium combined with budesonide has a significant effect in children with cough variant asthma and does not increase the incidence of adverse events.

Interleukin-6 suppression reduces tumour self-seeding by circulating tumour cells in a human osteosarcoma nude mouse model.

Tumour self-seeding by circulating tumour cells (CTCs) enhances tumour progression and recurrence. Previously, we demonstrated that tumour self-seeding by CTCs occurs in osteosarcoma and revealed that interleukin-6 (IL-6) may promote CTC attraction. Here, we investigated the underlying mechanisms of IL-6 in tumour self-seeding by CTCs. IL-6 suppression inhibited in vitro cell proliferation, migration, and invasion. In addition, rhIL-6 activated the Janus-activated kinase/signal transducers and activators of transcription 3 (JAK/STAT3) and mitogen-activated protein kinase/extracellular-signal regulated kinase1/2 (MAPK/ERK1/2) pathways in vitro. Both pathways increased cell proliferation, but only the JAK/STAT3 pathway promoted migration. Suppressing IL-6 inhibited in vivo tumour growth and metastasis. IL-6 suppression or JAK/STAT3 pathway inhibition reduced CTC seeding in primary tumours. Collectively, IL-6 promotes tumour self-seeding by CTCs in a nude mouse model. This finding may provide a novel strategy for future therapeutic interventions to prevent osteosarcoma progression and recurrence.

Establishment and characterization of a cisplatin­resistant human osteosarcoma cell line.

The aim of the present study was to establish a new cisplatin-resistant human osteosarcoma cell line and investigate its biological characteristics. The human osteosarcoma cell line SOSP-9607 was exposed to cisplatin by stepwisely increasing the concentrations in the medium to select for the drug-resistant subline, SOSP-9607/CDDP cells. The morphological features were observed using inverted microscopy. The growth curves of SOSP-9607 and SOSP-9607/CDDP cells were drawn to calculate the doubling time. FCM was also used to determine the distribution of the cell cycle. The MTT assay was performed to test the drug resistance of SOSP-9607 and SOSP-9607/CDDP cells. Transwell assay was used to examine the invasive capability of the SOSP-9607/CDDP and SOSP-9607 cells. RT-PCR was performed to determine the mRNA expression levels of drug resistance-related and apoptosis-related genes, MDR1, MRP1, MRP2, LRP, ABCG2, GST-π, Bcl-2 and Bax, in both cell lines. SOSP-9607/CDDP cells exhibited changes in morphology, proliferation rate, doubling time, cell cycle distribution and invasive capability as compared with the SOSP-9607 cells. SOSP-9607/CDDP cells were 6.24-fold resistant to cisplatin in comparison with the SOSP­9607 cells and also exhibited cross-resistance to methotrexate and adriamycin. SOSP-9607/CDDP cells overexpressed MRP1, MRP2 and GST-π. In conclusion, SOSP-9607/CDDP cells are invaluable tools with which to study the resistance of anticancer drugs and to identify the methods to overcome resistance.

Hypoxia promotes migration and induces CXCR4 expression via HIF-1α activation in human osteosarcoma.

BACKGROUND: Cellular adaptation to a hypoxic microenvironment is essential for tumor progression and is largely mediated by HIF-1α through coordinated regulation of hypoxia-responsive genes. The chemokine SDF-1α and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers. In this study, we investigated the response of osteosarcoma cells to hypoxia and the expression of CXCR4 and HIF-1α in human osteosarcoma specimens and explored the roles of CXCR4 and HIF-1α in the cell migration process. METHODOLOGY/PRINCIPAL FINDINGS: We performed immunohistochemistry, immunocytochemistry, quantitative real-time PCR, Western blots and fluorescent reporter assays to evaluate the correlation between CXCR4 and HIF-1α expression in human osteosarcoma specimens or SOSP-9607 cells under normoxic and hypoxic conditions. Transwell assays were used to assess cell migration under different conditions. Exposure of SOSP-9607 cells to hypoxic conditions resulted in significantly increased migration. When SOSP-9607 cells were subjected to hypoxic conditions, the mRNA and protein levels of CXCR4 were significantly increased in a time-dependent manner. Moreover, siHIF-1α significantly decreased the mRNA and protein levels of CXCR4 under hypoxia, whereas pcDNA-HIF-1α significantly increased the mRNA and protein levels of CXCR4 under normoxia. A luciferase reporter gene study showed that siHIF-1α reduced pGL3-CXCR4 luciferase activity. Furthermore, coexpression of HIF-1α and CXCR4 was significantly higher in patients with distant metastasis compared with those without metastasis. CONCLUSIONS/SIGNIFICANCE: The hypoxia-HIF-1α-CXCR4 pathway plays a crucial role during the migration of human osteosarcoma cells, and targeting this pathway might represent a novel therapeutic strategy for patients suffering from osteosarcoma.

MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma.

BACKGROUND: MicroRNAs are short regulatory RNAs that negatively modulate protein expression at a post-transcriptional and/or translational level and are deeply involved in the pathogenesis of several types of cancers. Specifically, microRNA-221 (miR-221) is overexpressed in many human cancers, wherein accumulating evidence indicates that it functions as an oncogene. However, the function of miR-221 in human osteosarcoma has not been totally elucidated. In the present study, the effects of miR-221 on osteosarcoma and the possible mechanism by which miR-221 affected the survival, apoptosis, and cisplatin resistance of osteosarcoma were investigated. METHODOLOGY/PRINCIPAL FINDINGS: Real-time quantitative PCR analysis revealed miR-221 was significantly upregulated in osteosarcoma cell lines than in osteoblasts. Both human osteosarcoma cell lines SOSP-9607 and MG63 were transfected with miR-221 mimic or inhibitor to regulate miR-221 expression. The effects of miR-221 were then assessed by cell viability, cell cycle analysis, apoptosis assay, and cisplatin resistance assay. In both cells, upregulation of miR-221 induced cell survival and cisplatin resistance and reduced cell apoptosis. In addition, knockdown of miR-221 inhibited cell growth and cisplatin resistance and induced cell apoptosis. Potential target genes of miR-221 were predicted using bioinformatics. Moreover, luciferase reporter assay and western blot confirmed that PTEN was a direct target of miR-221. Furthermore, introduction of PTEN cDNA lacking 3'-UTR or PI3K inhibitor LY294002 abrogated miR-221-induced cisplatin resistance. Finally, both miR-221 and PTEN expression levels in osteosarcoma samples were examined by using real-time quantitative PCR and immunohistochemistry. High miR-221 expression level and inverse correlation between miR-221 and PTEN levels were revealed in osteosarcoma tissues. CONCLUSIONS/SIGNIFICANCE: These results for the first time demonstrate that upregulation of miR-221 induces the malignant phenotype of human osteosarcoma whereas knockdown of miR-221 reverses this phenotype, suggesting that miR-221 could be a potential target for osteosarcoma treatment.

miR-34a inhibits the metastasis of osteosarcoma cells by repressing the expression of CD44.

Osteosarcoma is the most common type of malignant bone tumor in children and adolescents and approximately 30% of patients develop lung metastasis, which is the leading cause of mortality. In this study, we investigated the role of miR-34a in the invasion and metastasis of osteosarcoma cells by examining its expression level and functional pattern in these cells. miR-34a mimics were transfected into the highly metastatic subline, F5M2, and into the F4 subline with low metastatic potential of the paired human osteosarcoma cell line, SOSP­9607. Cell viability patterns, cell migration and alterations in gene expression levels were assessed by real-time PCR, and changes in protein levels were assessed by immunocytochemistry and western blot analysis. The ectopic overexpression of miR-34a significantly inhibited the migration and invasive ability of osteosarcoma cells by repressing the expression of CD44. These data suggest that miR-34a plays a tumor suppressor role in the metastasis of osteosarcoma cells by repressing the expression of CD44. Of note, studies have also suggested that the CD44 protein correlates with the metastatic potential of several malignant tumors. Therefore, it can be concluded that through the inhibition of CD44 expression levels, miR-34a plays a significant role in the migration and invasion of osteosarcoma cells.

miR-183 inhibits the metastasis of osteosarcoma via downregulation of the expression of Ezrin in F5M2 cells.

Osteosarcoma is the most common primary malignancy of bone in teenagers and approximately 30% of patients develop lung metastasis, which is the leading cause of mortality. Recent studies suggest that the Ezrin protein is correlated with the metastatic potential of several malignant tumors. In our study, ectopic overexpression of miR-183 repressed the expression levels of Ezrin and significantly inhibited the motility and invasion of osteosarcoma cells. This suggests that miR-183 may possibly play a tumor suppressor role in the metastasis of osteosarcoma by downregulating Ezrin expression levels. These findings show that through inhibition of Ezrin expression levels, miR-183 is significantly involved in cell migration and invasion of osteosarcoma.

A systematic review of modern metal-on-metal total hip resurfacing vs standard total hip arthroplasty in active young patients.

This systematic review compared 2 treatments for hip disease in active young patients: modern metal-on-metal total hip resurfacing and standard total hip arthroplasty. We conducted a literature search to identify relevant randomized and clinical controlled trials and included 968 patients from 4 trials in our analysis. Our results indicated increased rates of revision, femoral neck fractures, and component loosening among patients who received modern metal-on-metal hip resurfacing. No significant differences in the rates of mortality, dislocation, or deep hip joint infection were found between treatment groups. Hip function scores were similar between the 2 groups, but the resurfacing group showed higher activity levels. These results have provided insufficient evidence to determine whether modern metal-on-metal total hip resurfacing offers clinical advantages over standard total hip arthroplasty.