Poor prognosis of cancers, including hepatocellular carcinoma (HCC), is mainly associated with metastasis; however, the underlying mechanisms remain poorly understood. This article investigates the role of lysyl oxidase-like 2 (LOXL-2) in the biology of HCC metastasis. First, we showed that HCC metastasis relies on a collagen-modifying enzyme, LOXL2, which was significantly overexpressed in tumorous tissues and sera of HCC patients, indicating that LOXL2 may be a good diagnostic marker for HCC patients. Second, we delineated a complex, interlinked signaling network that involves multiple regulators, including hypoxia, transforming growth factor beta (TGF-β), and microRNAs (miRNAs), converging to control the expression of LOXL2. We found not only that LOXL2 was regulated by hypoxia/hypoxia-inducible factor 1 alpha (HIF-1α), but also that TGF-β activated LOXL2 transcription through mothers against decapentaplegic homolog 4 (Smad4), whereas two frequently underexpressed miRNA families, miR-26 and miR-29, cooperatively suppressed LOXL2 transcription through interacting with the 3' untranslated region of LOXL2. Third, we demonstrated the imperative roles of LOXL2 in modifying the extracellular matrix components in the tumor microenvironment and metastatic niche of HCC. LOXL2 promoted intrahepatic metastasis by increasing tissue stiffness, thereby enhancing the cytoskeletal reorganization of HCC cells. Furthermore, LOXL2 facilitated extrahepatic metastasis by enhancing recruitment of bone-marrow–derived cells to the metastatic site. Conclusion : These findings integrate the clinical relevance, molecular regulation, and functional implications of LOXL2 in HCC metastasis. (Hepatology 2014;60:1645–1658)

A nonlinear finite element model was developed to investigate the biomechanics of indentation, particularly the influence of friction and large deformation on the calculation of the effective Young's modulus from the cylindrical, flat-ended indentation test of soft tissues. A new kappa table was given for calculation of the effective Young's modulus to account for the effects of layered geometry with consideration of the larger deformation. The results indicate that the effect of friction on the calculation of Young's modulus becomes significant with a large aspect ratio and with a large Poisson's ratio. It is found that the factor kappa increases almost proportionally to the increase of the indentation depth, especially obvious with a larger Poisson's ratio v and a larger aspect ratio a/h.

Electromyography (EMG) has been widely used for the assessment of musculoskeletal functions and the control of electrical prostheses, which make use of the EMG signal generated by the contraction of the residual muscles. In spite of the successful applications of EMG in different fields, it has some inherent limitations, such as the difficulty to differentiate the actions of neighboring muscles and to collect signals from deep muscles using the surface EMG. The majority of current EMG controlled prostheses can only provide sequential on-off controls using signals from two groups of muscles, so the users are required to put many conscious efforts in monitoring the speed and range of motion of the terminal devices being controlled. Recently, many alternative signals based on the detection of dimensional changes of muscles or tendons during actions have been reported. The objective of this study was to investigate the potential of the dimensional change of muscles detected using sonography for musculoskeletal assessment and control. A portable B-mode ultrasound scanner was used to collect the dynamic ultrasound images of the forearm muscles of six normally limbed young adults and three amputee subjects. A motion analysis system was used to collect the movement of the wrist angle during the experiments for the normal subjects. It was demonstrated that the morphological changes of forearm muscles during actions can be successfully detected by ultrasound and linearly correlated (R(2)=0.876+/-0.042, mean+/-S.D.) with the wrist angle. We named these sonographically detected signals about the architectural change of the muscle as sonomyography (SMG). The mean ratio between the wrist angle and the percentage deformation of the forearm muscle was 7.2+/-3.7 degrees /% for the normal subjects. The intraclass correlation coefficient (ICC) of this ratio among the three repeated tests was 0.868. The SMG signals from the residual forearms were also successfully detected when the three amputee subjects contracted their residual muscles. The results demonstrated that SMG had potentials for the musculoskeletal control and assessment.

Radiographic evaluation for patients with scoliosis using Cobb method is the current gold standard, but radiography has radiation hazards. Several groups have recently demonstrated the feasibility of using 3D ultrasound for the evaluation of scoliosis. Ultrasound imaging is radiation-free, comparatively more accessible, and inexpensive. However, a reliable and valid 3D ultrasound system ready for clinical scoliosis assessment has not yet been reported. Scolioscan is a newly developed system targeted for scoliosis assessment in clinics by using coronal images of spine generated by a 3D ultrasound volume projection imaging method. The aim of this study is to test the reliability of spine deformity measurement of Scolioscan and its validity compared to the gold standard Cobb angle measurements from radiography in adolescent idiopathic scoliosis (AIS) patients. Prospective study divided into two stages: 1) Investigation of intra- and inter- reliability between two operators for acquiring images using Scolioscan and among three raters for measuring spinal curves from those images; 2) Correlation between the Cobb angle obtained from radiography by a medical doctor and the spine curve angle obtained using Scolioscan (Scolioscan angle). The raters for ultrasound images and the doctors for evaluating radiographic images were mutually blinded. The two stages of tests involved 20 (80 % females, total of 26 angles, age of 16.4 ± 2.7 years, and Cobb angle of 27.6 ± 11.8°) and 49 (69 % female, 73 angles, 15.8 ± 2.7 years and 24.8 ± 9.7°) AIS patients, respectively. Intra-class correlation coefficients (ICC) and Bland-Altman plots and root-mean-square differences (RMS) were employed to determine correlations, which interpreted based on defined criteria. We demonstrated a very good intra-rater and intra-operator reliability for Scolioscan angle measurement with ICC larger than 0.94 and 0.88, respectively. Very good inter-rater and inter-operator reliability was also demonstrated, with both ICC larger than 0.87. For the thoracic deformity measurement, the RMS were 2.5 and 3.3° in the intra- and inter-operator tests, and 1.5 and 3.6° in the intra- and inter-rater tests, respectively. The RMS differences were 3.1, 3.1, 1.6, 3.7° in the intra- and inter-operator and intra- and inter-rater tests, respectively, for the lumbar angle measurement. Moderate to strong correlations (R2 > 0.72) were observed between the Scolioscan angles and Cobb angles for both the thoracic and lumbar regions. It was noted that the Scolioscan angle slightly underestimated the spinal deformity in comparison with Cobb angle, and an overall regression equation y = 1.1797x (R2 = 0.76) could be used to translate the Scolioscan angle (x) to Cobb angle (y) for this group of patients. The RMS difference between Scolioscan angle and Cobb angle was 4.7 and 6.2°, with and without the correlation using the overall regression equation. We showed that Scolioscan is reliable for measuring coronal deformity for patients with AIS and appears promising in screening large numbers of patients, for progress monitoring, and evaluation of treatment outcomes. Due to it being radiation-free and relatively low-cost, Scolioscan has potential to be widely implemented and may contribute to reducing radiation dose during serial monitoring.

Muscle fatigue is an exercise-induced reduction in maximal voluntary muscle force. As the surface electromyography (SEMG) can be used to estimate the features of neuromuscular activations associated with muscle contractions, it has been widely employed as an objective tool to evaluate muscle fatigue. On the other hand, ultrasound imaging can inherently provide the morphological information of individual muscle, thus the architectural changes of muscles during fatigue can be obtained. In this study, we demonstrated the feasibility of using the dimensional change of muscles detected by ultrasound images, named as sonomyography (SMG), to characterize the behavior of muscles when they were in fatigue. The SEMG signals of the muscles were also recorded simultaneously and used for comparison. The right biceps brachii muscles of 8 normal young male adult subjects were tested for 30s under 80% of the maximal voluntary isometric contraction. The muscle fatigue was indicated by the change of the root-mean-square (RMS) and median frequency (MDF) of the SEMG signals. The results showed that the SEMG RMS had a linear increase with time with a rate of 2.9+/-1.9%/s (mean+/-S.D.), while the MDF decreased linearly with a rate of -0.60+/-0.26Hz/s. The muscle thickness, detected from the ultrasound images, continuously increased during the muscle fatigue but with a nonlinear increase with time, which was rapid during the initial 8.1+/-2.1s with a mean deformation rate of 0.30+/-0.19%/s and then became slower with a rate of 0.067+/-0.024%/s up to 20s after the contraction. The muscle deformation at 20s was 3.5+/-1.6%. The results demonstrated that the architectural change of muscles detected using SMG could potentially provide complementary information for SEMG for the muscle fatigue assessment.