Design, fabrication and experiments of a hydraulic active-passive hybrid prosthesis knee.

BACKGROUND: Due to low friction, passive mechanical prostheses move compliantly followed by the stump and are used widely. Advanced semi-active prostheses can both move passively like passive prostheses and provide active torque under specific conditions. However, the current mechanical-hydraulic coupling driven semi-active prostheses, in order to meet the low passive friction requirements with a low active transmission ratio, lead to a significant problem of insufficient active torque. OBJECTIVE: A hybrid active and passive prosthesis was developed to solve the incompatibility problem of low passive friction and high active driving torque of semi-active prostheses. METHODS: The mechanical structure and control strategy of the prosthesis were demonstrated. The performance of the prosthesis was tested by bench and human tests. RESULTS: Passive subsystem damping adjustment ranges from 0.4 N⋅(mm/s)-1 to 300 N⋅(mm/s)-1. The switching time between the damping and the active subsystem is 32 ± 2 ms. The continuous active torque output is more than 24 Nm. In level walking, the peak torque is about 28 Nm. CONCLUSION: The proposed active-passive hybrid hydraulic prosthesis could satisfy both low passive friction and high active actuation.

Exosome-Transmitted miR-25 Induced by H. pylori Promotes Vascular Endothelial Cell Injury by Targeting KLF2.

Background: Increasing evidence has shown that Helicobacter pylori is associated with coronary heart disease (CHD); however, the underlying mechanism remains unclear. Methods: The expression of miR-25 and mRNAs was measured using qRT-PCR. Protein levels were detected using western blotting and exosomes were assessed with an electron microscope. The target gene of miR-25 was identified using the luciferase report system. Results:H. pylori infection increased the expression of miR-25 in gastric epithelial cells and was associated with increased levels of exosome-transmitted miR-25 in human peripheral blood. Mechanistic investigation showed the Kruppel-like factor 2 (KLF2) was a direct target of exosome-transmitted miR-25 in vascular endothelial cells. In addition, the miR-25/KLF2 axis regulated the NF-κB signaling pathway, resulting in increased expression of interleukin 6 (IL6), monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). Conclusion: Our findings suggest that the miR-25/KLF2 axis may be a potential therapeutic target for H. pylori-associated CHD. Furthermore, high levels of exosome-transmitted miR-25 in peripheral blood may pose a potential risk for CHD.

MicroRNA­146a inhibits the inflammatory responses induced by interleukin­17A during the infection of Helicobacter pylori.

Helicobacter pylori (H. pylori) infection is the major cause of chronic active gastritis and peptic ulcer disease. Upregulation of IL­17A is associated with H. pylori infection in the gastric mucosa; however, the factors involved in the regulation of interleukin (IL)­17A­induced inflammatory responses in H. pylori­associated gastritis remain unknown. MicroRNAs (miRNAs) serve as key post­transcriptional regulators of gene expression and are associated with the H. pylori infection. The present study aimed to analyze the effects of IL­17A on the expression of miR­146a upon infection with H. pylori, as well as to identify the possible impact of miR­146a dysregulation on the inflammatory response in vivo and in vitro. Reverse transcription­quantitative polymerase chain reaction analysis was used to determine the expression levels of miR­146a in gastric epithelial cells upon IL­17A stimulation. The effects of miR­146a mimics on IL­17A­induced inflammatory responses in SGC­7901 cells were evaluated. The effects of miR­146a mimics on the expression levels of IL­1 receptor­associated kinase 1 (IRAK1) and tumor necrosis factor receptor­associated factor 6 (TRAF6) upon IL­17A treatment were analyzed, and the IL­17A­stimulated inflammation following the silencing of IRAK1 and TRAF6 was observed. In addition, the correlation between miR­146a and IL­17A in human gastric mucosa with H. pylori was examined. The results indicated that IL­17A­induced miR­146a may regulate the inflammatory response during the infection of H. pylori in a nuclear factor­κB­dependent manner. Furthermore, the expression of miR­146a and IL­17A are positively correlated in human gastric mucosa infected with H. pylori. These data suggested that miR­146a may serve as a biomarker or therapeutic target in gastritis therapy.

Numerical Investigation of the Effect of Additional Pulmonary Blood Flow on Patient-Specific Bilateral Bidirectional Glenn Hemodynamics.

The effect of additional pulmonary blood flow (APBF) on the hemodynamics of bilateral bidirectional Glenn (BBDG) connection was marginally discussed in previous studies. This study assessed this effect using patient-specific numerical simulation. A 15-year-old female patient who underwent BBDG was enrolled in this study. Patient-specific anatomy, flow waveforms, and pressure tracings were obtained using computed tomography, Doppler ultrasound technology, and catheterization, respectively. Computational fluid dynamic simulations were performed to assess flow field and derived hemodynamic metrics of the BBDG connection with various APBF. APBF showed noticeable effects on the hemodynamics of the BBDG connection. It suppressed flow mixing in the connection, which resulted in a more antegrade flow structure. Also, as the APBF rate increases, both power loss and reflux in superior venae cavae (SVCs) monotonically increases while the flow ratio of the right to the left pulmonary artery (RPA/LPA) monotonically decreases. However, a non-monotonic relationship was observed between the APBF rate and indexed power loss. A high APBF rate may result in a good flow ratio of RPA/LPA but with the side effect of bad power loss and remarkable reflux in SVCs, and vice versa. A moderate APBF rate could be favourable because it leads to an optimal indexed power loss and achieves the acceptable flow ratio of RPA/LPA without causing severe power loss and reflux in SVCs. These findings suggest that patient-specific numerical simulation should be used to assist clinicians in determining an appropriate APBF rate based on desired outcomes on a patient-specific basis.

Helicobacter pylori CagA Protein Negatively Regulates Autophagy and Promotes Inflammatory Response via c-Met-PI3K/Akt-mTOR Signaling Pathway.

Cytotoxin-associated-gene A (CagA) of Helicobacter pylori (H. pylori) is a virulence factor that plays critical roles in H. pylori-induced gastric inflammation. In the present study, gastric biopsies were used for genotyping cagA and vacA genes, determining the autophagic activity, and the severity of gastric inflammation response. It was revealed that autophagy in gastric mucosal tissues infected with cagA+H. pylori strains was lower than the levels produced by cagA-H. pylori strains, accompanied with accumulation of SQSTM1 and decreased LAMP1 expression. In vitro, deletion mutant of cagA gene resulted in increased autophagic activity, and decreased expression of SQSTM1 and cytokines, whereas over-expression of CagA down-regulated the starvation-induced autophagy, and induced more production of the cytokines. Moreover, the production of the cytokines was increased by inhibition of autophagy, but decreased by enhancement of autophagy. Deletion of CagA decreased the ability to activate Akt kinase at Ser-473 site and increased autophagy. c-Met siRNA significantly affected CagA-mediated autophagy, and decreased the level of p-Akt, p-mTOR, and p-S6. Both c-Met siRNA and MK-2206 could reverse inflammatory response. H. pylori CagA protein negatively regulates autophagy and promotes the inflammation in H. pylori infection, which is regulated by c-Met-PI3K/Akt-mTOR signaling pathway activation.

Distribution of lung blood on modified bilateral Glenn shunt evaluated by Tc-99m-MAA lung perfusion scintigraphy: A retrospective study.

The aim of the present study was to determine the distribution of lung blood in a modified bilateral Glenn procedure designed in our institute with lung perfusion scintigraphy. Sixteen consecutive patients who underwent modified bilateral Glenn operation from 2011 to 2014 were enrolled in the study. The control group consisted of 7 patients who underwent bidirectional Glenn shunt. Radionuclide lung perfusion scintigraphy was performed using Tc-99m-macro aggregated albumin (MAA) in all patients. For the patients in modified bilateral Glenn group, the time at which the radioactivity accumulation peaked did not differ significantly between the right and left lung field (t = 0.608, P = 0.554). The incidence of perfusion abnormality in each lung lobe also did not differ significantly (P = 0.426 by Fisher exact test). The radioactive counts were higher in the right lung than in the left lung, but the difference was not statistically significant (t = 1.502, P = 0.157). Radioactive perfusion in the lower lung field was significantly greater than that in the upper field (t = 4.368, P < 0.001). Compared with that in the bidirectional Glenn group, the ratio of radioactivity in the right lung to that in left lung was significantly lower in the modified bilateral Glenn group (t = 3.686, P = 0.002). Lung perfusion scintigraphy confirmed the benefit of the modified bilateral Glenn shunt with regard to more balanced blood perfusion in both lungs.

Nicotine Induces Cardiomyocyte Hypertrophy Through TRPC3-Mediated Ca2+/NFAT Signalling Pathway.

BACKGROUND: Nicotine is thought to be an important risk factor for the development of cardiovascular diseases. However, the effects of nicotine on cardiomyocyte hypertrophy are poorly understood. The present study was designed to explore the role of nicotine in cardiomyocyte hypertrophy and its underlying mechanism. METHODS: We used primary cardiomyocytes isolated from Wistar rats to examine the effects of nicotine on intracellular Ca2+ mobilization and hypertrophy determined by immunofluorescence, quantitative polymerase chain reaction, and western blot analysis. A luciferase reporter assay was used to examine the activity of NFAT signalling. RESULTS: We found that nicotine caused cardiomyocyte hypertrophy, which was accompanied by increased intracellular Ca2+. Nicotine-enhanced intracellular Ca2+ concentration ([Ca2+]i) was significantly abolished by store-operated Ca2+ entry (SOCE) and TRPC inhibitors. Knockdown of TRPC3 significantly decreased nicotine-induced SOCE and hypertrophy. Moreover, calcineurin-nuclear factor of activated T cells (NFAT) is involved in TRPC3-mediated Ca2+ signalling and cardiomyocyte hypertrophy. Notably, upregulation of TRPC3 by nicotine requires TRPC3-mediated Ca2+ influx and calcineurin-NFAT signalling activation. CONCLUSIONS: Our findings demonstrate that the prohypertrophic effect of nicotine on cardiomyocytes is dependent on enhanced TRPC3 expression through a calcium-dependent regulatory loop, which could become a potential target for prevention and treatment of cardiac hypertrophy.

Somatic copy number losses on chromosome 9q21.33q22.33 encompassing the PTCH1 loci associated with cardiac fibroma.

Cardiac fibroma is an extremely rare benign tumor that remains poorly characterized genetically. Somatic copy number alterations are common in tumors and have been defined as a crucial factor leading to tumors. In this study, we present a child diagnosed with cardiac fibroma with somatic copy number losses of a total of three discontinuous segments from 9q21.33 to 9q22.33, including a mosaic deletion of PTCH1. PTCH1 has been associated with sporadic cardiac fibroma. Sequencing analysis of the PTCH1 gene has not revealed any causative mutation. Quantitative PCR analysis of PTCH1 further confirms somatic copy number losses. Our data narrow down the critical causative deletions for sporadic cardiac fibroma to a region more precise than any other previously reported one. Our results suggest important roles of somatic copy number losses on chromosome 9q21.33q22.33 in the development of sporadic cardiac fibroma; these findings may provide a better understanding of sporadic cardiac fibroma pathogenesis and contribute to the identification of novel diagnostic biomarkers of this neoplasm. .

Inhibition of Autophagy by MiR-30A Induced by Mycobacteria tuberculosis as a Possible Mechanism of Immune Escape in Human Macrophages.

The regulatory mechanism of miRNA induction in response to Mycobacterium tuberculosis (MTB) infection has not been clearly established. Autophagy has recently been identified as an effective way to control intracellular survival of MTB. In the present study, we demonstrate a novel role of miR-30A in the negative regulation of the autophagy-mediated anti-MTB response. We found that overexpression of miR-30A suppresses the elimination of intracellular MTB through the inhibition of autophagy. Furthermore, there was a negative correlation between concentrations of miR-30A and beclin-1 in MTB positive patients and miR-30A expression decreased after anti-TB treatment. Our results indicate that miR-30A plays a key role in immune response against MTB and, therefore, may serve as a potential target for future treatments of tuberculosis infection.

Association between the NFKB1-94ins/del ATTG polymorphism and cancer risk: an updated meta-analysis.

To assess the effect of the NFKB1 -94ins/del polymorphism on cancer, we conducted a meta-analysis based on 25 studies including 8,750 cases and 9,170 controls. Overall, the -94ins/del polymorphism was associated with cancer risk in the pooled analysis and in Asian population, whereas no association was observed in Caucasian population. Stratified analysis by subtypes of cancer showed that the -94ins/del polymorphism was associated with oral squamous cell carcinoma and ovarian cancer risk, but had no association with colorectal cancer, bladder cancer, and renal cell cancer. Our meta-analysis suggests the NFKB1 -94ins/del polymorphism affects cancer susceptibility, and the association is ethnic-specific.

Boiler Briquette Coal versus Raw Coal: Part I-Stack Gas Emissions.

Stack gas emissions were characterized for a steam-generating boiler commonly used in China. The boiler was tested when fired with a newly formulated boiler briquette coal (BB-coal) and when fired with conventional raw coal (R-coal). The stack gas emissions were analyzed to determine emission rates and emission factors and to develop chemical source profiles. A dilution source sampling system was used to collect PM on both Teflon membrane filters and quartz fiber filters. The Teflon filters were analyzed gravimetrically for PM10 and PM2.5 mass concentrations and by X-ray fluorescence (XRF) for trace elements. The quartz fiber filters were analyzed for organic carbon (OC) and elemental carbon (EC) using a thermal/optical reflectance technique. Sulfur dioxide was measured using the standard wet chemistry method. Carbon monoxide was measured using an Orsat combustion analyzer. The emission rates of the R-coal combustion (in kg/hr), determined using the measured stack gas concentrations and the stack gas emission rates, were 0.74 for PM10, 0.38 for PM25, 20.7 for SO2, and 6.8 for CO, while those of the BB-coal combustion were 0.95 for PM10, 0.30 for PM2 5, 7.5 for SO2, and 5.3 for CO. The fuel-mass-based emission factors (in g/kg) of the R-coal, determined using the emission rates and the fuel burn rates, were 1.68 for PM10, 0.87 for PM25, 46.7 for SO2, and 15 for CO, while those of the BB-coal were 2.51 for PM10, 0.79 for PM2.5, 19.9 for SO2, and 14 for CO. The task-based emission factors (in g/ton steam generated) of the R-coal, determined using the fuel-mass-based emission factors and the coal/ steam conversion factors, were 0.23 for PM10, 0.12 for PM2.5, 6.4 for SO2, and 2.0 for CO, while those of the BB-coal were 0.30 for PM10, 0.094 for PM2.5, 2.4 for SO2, and 1.7 for CO. PM10 and PM2.5 elemental compositions are also presented for both types of coal tested in the study.