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To investigate the effects and mechanisms of irisin, a newly discovered myokine, in cartilage development, osteoarthritis (OA) pathophysiology and its therapeutic potential for treating OA we applied the following five strategical analyses using (1) murine joint tissues at different developmental stages; (2) human normal and OA pathological tissue samples; (3) experimental OA mouse model; (4) irisin gene knockout (KO) and knock in (KI) mouse lines and their cartilage cells; (5) in vitro mechanistic experiments. We found that Irisin was involved in all stages of cartilage development. Both human and mouse OA tissues showed a decreased expression of irisin. Intra-articular injection of irisin attenuated ACLT-induced OA progression. Irisin knockout mice developed severe OA while irisin overexpression in both irisin KI mice and intraarticular injection of irisin protein attenuated OA progression. Irisin inhibited inflammation and promoted anabolism in chondrogenic ADTC5 cells. Proliferative potential of primary chondrocytes from KI mice was found to be enhanced, while KO mice showed an inhibition under normal or inflammatory conditions. The primary chondrocytes from irisin KI mice showed reduced expression of inflammatory factors and the chondrocytes isolated from KO mice showed an opposite pattern. In conclusion, it is the first time to show that irisin is involved in cartilage development and OA pathogenesis. Irisin has the potential to ameliorate OA progression by decreasing cartilage degradation and inhibiting inflammation, which could lead to the development of a novel therapeutic target for treating bone and cartilage disorders including osteoarthritis.

Background The aim of this study was to investigate a novel method to treat coronary artery aneurysms(CAAs).Methods Three CAAs patients who underwent single or double bare-metal stent implantation were recruited. The CAAs and parent artery diameters were measured for model construction. Single- and double-stent implantation were simulated, and the changes in the CAAs haemodynamics after stenting were analysed. Results In Case 1, the flow velocity in the single-stent model was significantly lower than that in the double-stent model (0.0046±0.013 vs 0.0050±0.011, pConclusion Application of the single or double bare-metal stent technique, according to the neck diameter of the coronary artery aneurysms, can effectively change the flow in vessels and aneurysm haemodynamics to achieve occlusion.Trail registration: Clinicaltrails, NCT04265989. Registered 12 February 2020, https://clinicaltrials.gov/ct2/show/NCT04265989?term=NCT04265989&draw=2&rank=1

TNFα/TNFR signaling plays a critical role in the pathogenesis of various inflammatory and autoimmune diseases, and anti-TNFα therapies have been accepted as the effective approaches for treating several autoimmune diseases. Progranulin (PGRN), a multi-faced growth factor-like molecule, directly binds to TNFR1 and TNFR2, particularly to the latter with higher affinity than TNFα. PGRN derivative Atsttrin is composed of three TNFR-binding domain of PGRN and exhibits even better therapeutic effects than PGRN in several inflammatory disease models, including collagen-induced arthritis. Herein we describe the detailed methodology of using (1) ELISA-based solid phase protein-protein interaction assay to demonstrate the direct binding of Atsttrin to TNFR2 and its inhibition of TNFα/TNFR2 interaction; and (2) tartrate-resistant acid phosphatase (TRAP) staining of in vitro osteoclastogenesis to reveal the cell-based anti-TNFα activity of Atsttrin. Using the protocol described here, the investigators should be able to reproducibly detect the physical inhibition of TNFα binding to TNFR and the functional inhibition of TNFα activity by Atsttrin and various kinds of TNF inhibitors.

TNFR1 and TNFR2 have received prominent attention because of their dominance in the pathogenesis of inflammation and autoimmunity. TNFR1 has been extensively studied and primarily mediates inflammation. TNFR2 remains far less studied, although emerging evidences demonstrate that TNFR2 plays an anti-inflammatory and immunoregulatory role in various conditions and diseases. Herein, we report that TNFR2 regulates macrophage polarization, a highly dynamic process controlled by largely unidentified intracellular regulators. Using biochemical co-purification and mass spectrometry approaches, we isolated the signaling molecule 14-3-3e as a component of TNFR2 complexes in response to progranulin stimulation in macrophages. In addition, 14-3-3e was essential for TNFR2 signaling-mediated regulation of macrophage polarization and switch. Both global and myeloid-specific deletion of 14-3-3e resulted in exacerbated inflammatory arthritis and counteracted the protective effects of progranulin-mediated TNFR2 activation against inflammation and autoimmunity. TNFR2/14-3-3e signaled through PI3K/Akt/mTOR to restrict NF-κB activation while simultaneously stimulating C/EBPβ activation, thereby instructing macrophage plasticity. Collectively, this study identifies 14-3-3e as a previously-unrecognized vital component of the TNFR2 receptor complex and provides new insights into the TNFR2 signaling, particularly its role in macrophage polarization with therapeutic implications for various inflammatory and autoimmune diseases with activation of the TNFR2/14-3-3e anti-inflammatory pathway.

Purpose—Image-based computational fluid dynamics (CFD) is widely used to predict intracranial aneurysm wall shear stress (WSS), particularly with the goal of improving rupture risk assessment. Nevertheless, concern has been expressed over the variability of predicted WSS and inconsistent associations with rupture. Previous challenges, and studies from individual groups, have focused on individual aspects of the image-based CFD pipeline. The aim of this Challenge was to quantify the total variability of the whole pipeline. Methods—3D rotational angiography image volumes of five middle cerebral artery aneurysms were provided to participants, who were free to choose their segmentation methods boundary conditions, and CFD solver and settings. Participants were asked to fill out a questionnaire about their solution strategies and experience with aneurysm CFD, and provide surface distributions of WSS magnitude, from which we objectively derived a variety of hemodynamic parameters. Results—A total of 28 datasets were submitted, from 26 teams with varying levels of self-assessed experience. Wide variability of segmentations, CFD model extents, and inflow rates resulted in interquartile ranges of sac average WSS up to 56%, which reduced to < 30% after normalizing by parent artery WSS. Sac-maximum WSS and low shear area were more variable, while rank-ordering of cases by low or high shear showed only modest consensus among teams. Experience was not a significant predictor of variability. Conclusions—Wide variability exists in the prediction of intracranial aneurysm WSS. While segmentation and CFD solver techniques may be difficult to standardize across groups, our findings suggest that some of the variability in image-based CFD could be reduced by establishing guidelines for model extents, inflow rates, and blood properties, and by encouraging the reporting of normalized hemodynamic parameters. Fil: Valen-Sendstad, Kristian. Simula Research Laboratory and Center for Cardiological Innovation; Noruega Fil: Bergersen, Aslak W.. University of Oslo; Noruega Fil: Shimogonya, Yuji. Nihon University; Japón Fil: Goubergrits, Leonid. Charite´ – Universita¨tsmedizin Berlin; Alemania Fil: Bruening, Jan. Charité – Universitätsmedizin Berlin; Alemania Fil: Pallares, Jordi. Universitat Rovira I Virgili; España Fil: Cito, Salvatore. Universitat Rovira I Virgili; España Fil: Piskin, Senol. University Of Texas At San Antonio.; Estados Unidos Fil: Pekkan, Kerem. Koc University; Turquía Fil: Geers, Arjan J.. Universitat Pompeu Fabra; España Fil: Larrabide, Ignacio. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Grupo de Plasmas Densos Magnetizados. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Grupo de Plasmas Densos Magnetizados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Rapaka, Saikiran. Siemens Medical Solutions USA Inc; Estados Unidos Fil: Mihalef, Viorel. Siemens Medical Solutions USA Inc; Estados Unidos Fil: Fu, Wenyu. Beijing Union University; China Fil: Qiao, Aike. Beijing University of Technology; China Fil: Jain, Kartik. Simula Research Laboratory and Center for Cardiological Innovation; Noruega. University of Siegen; Alemania. University of Zürich; Suiza Fil: Roller, Sabine. University of Siegen; Alemania Fil: Mardal, Kent-Andre. Simula Research Laboratory and Center for Cardiological Innovation; Noruega. University of Oslo; Noruega Fil: Kamakoti, Ramji. Dassault Systemes; Francia Fil: Spirka, Thomas. Simpleware Software Solutions; Reino Unido Fil: Ashton, Neil. University of Oxford; Reino Unido Fil: Revell, Alistair. University of Manchester; Reino Unido Fil: Aristokleous, Nicolas. University of Limerick; Irlanda Fil: Houston, J. Graeme. University of Dundee; Reino Unido Fil: Tsuji, Masanori. Mie Chuo Medical Center; Japón Fil: Ishida, Fujimaro. Mie Chuo Medical Center; Japón Fil: Menon, Prahlad G.. University of Pittsburgh; Estados Unidos Fil: Browne, Leonard D.. University of Limerick; Irlanda Fil: Broderick, Stephen. University of Limerick; Irlanda Fil: Shojima, Masaaki. University of Tokyo; Japón Fil: Koizumi, Satoshi. University of Tokyo; Japón Fil: Barbour, Michael. University of Washington; Estados Unidos Fil: Aliseda, Alberto. University of Washington; Estados Unidos Fil: Morales, Hernán G.. Medisys - Philips Research Paris; Francia Fil: Lefèvre, Thierry. Medisys - Philips Research Paris; Francia Fil: Hodis, Simona. Texas A&M University - Kingsville; Estados Unidos Fil: Al-Smadi, Yahia M.. Jordan University of Science and Technology; Jordania Fil: Tran, Justin S.. Stanford University; Estados Unidos Fil: Marsden, Alison L.. Stanford University; Estados Unidos Fil: Vaippummadhom, Sreeja. EinNel Technlogies; India Fil: Einstein, G. Albert. EinNel Technlogies; India Fil: Brown, Alistair G.. Siemens PLM Software; Estados Unidos Fil: Debus, Kristian. Siemens PLM Software; Estados Unidos Fil: Niizuma, Kuniyasu. Tohoku University; Japón Fil: Rashad, Sherif. Tohoku University; Japón Fil: Sugiyama, Shin-ichiro. Kohnan Hospital; Japón Fil: Owais Khan, M.. University of Toronto; Canadá Fil: Updegrove, Adam R.. University of California at Berkeley; Estados Unidos Fil: Shadden, Shawn C.. University of California at Berkeley; Estados Unidos Fil: Cornelissen, Bart M. W.. Academic Medical Center; Países Bajos Fil: Majoie, Charles B. L. M.. Academic Medical Center; Países Bajos Fil: Berg, Philipp. University of Magdeburg; Alemania Fil: Saalfield, Sylvia. University of Magdeburg; Alemania Fil: Kono, Kenichi. Wakayama Rosai Hospital; Japón Fil: Steinman, David A.. University of Toronto; Canadá

ObjectiveTumour necrosis factor alpha (TNF-α) signalling plays a central role in the pathogenesis of various autoimmune diseases, particularly inflammatory arthritis. This study aimed to repurpose clinically approved drugs as potential inhibitors of TNF-α signalling in treatment of inflammatory arthritis.MethodsIn vitro and in vivo screening of an Food and Drug Administration (FDA)-approved drug library; in vitro and in vivo assays for examining the blockade of TNF actions by fexofenadine: assays for defining the anti-inflammatory activity of fexofenadine using TNF-α transgenic (TNF-tg) mice and collagen-induced arthritis in DBA/1 mice. Identification and characterisation of the binding of fexofenadine to cytosolic phospholipase A2 (cPLA2) using drug affinity responsive target stability assay, proteomics, cellular thermal shift assay, information field dynamics and molecular dynamics; various assays for examining fexofenadine inhibition of cPLA2 as well as the dependence of fexofenadine’s anti-TNF activity on cPLA2.ResultsSerial screenings of a library composed of FDA-approved drugs led to the identification of fexofenadine as an inhibitor of TNF-α signalling. Fexofenadine potently inhibited TNF/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) signalling in vitro and in vivo, and ameliorated disease symptoms in inflammatory arthritis models. cPLA2 was isolated as a novel target of fexofenadine. Fexofenadine blocked TNF-stimulated cPLA2 activity and arachidonic acid production through binding to catalytic domain 2 of cPLA2 and inhibition of its phosphorylation on Ser-505. Further, deletion of cPLA2 abolished fexofenadine’s anti-TNF activity.ConclusionCollectively, these findings not only provide new insights into the understanding of fexofenadine action and underlying mechanisms but also provide new therapeutic interventions for various TNF-α and cPLA2-associated pathologies and conditions, particularly inflammatory rheumatic diseases.

Background Functional heterogeneity is a hallmark of macrophages, which can classified into 2 major phenotypes with opposite role in inflammation termed M1 (inflammatory or classically activated) macrophages and M2 (alternatively activated) macrophages. In addition, M1-M2 polarisation of macrophages is a highly dynamic process and the phenotype of polarised macrophages can be switched under physiological and pathological conditions. Progranulin (PGRN), a multiple functional growth factor, binds to TNF receptor 2 (TNFR2) and activates the protective and anti-inflammatory pathway in inflammatory arthritis. In addition, 14–3–3e was identified as a component of PGRN/TNFR2 complexes in Raw264.7 macrophages. Objectives In this study, we examined whether 14–3–3e regulated macrophage polarisation and if so, whether this was important for PGRN’s anti-inflammatory action in inflammatory arthritis. Methods LysMCre and14–3–3e F/F mouse line was obtained from Jackson Laboratory. Results : 14–3–3e regulates macrophage polarisationin vitro. We found that 14–3–3e deficiency enhanced M1 while inhibited M2 polarisation (figure 1a, b). Interestingly, PGRN showed reverse effects on macrophage polarisation. In addition, PGRN’s effects were largely lost in 14–3–3e deficient BMDMs (figure 1a, b). Together, these data indicate that 14–3–3e is a critical downstream mediator of PGRN regulation of macrophage polarisation. Macrophage-specific 14–3–3e contributes to control of inflammatory arthritis and is critical for PGRN’s anti-inflammatory action. We then explored the role of macrophage-specific 14–3–3e in inflammatory arthritis and whether PGRN’s anti-inflammatory activity depended on 14–3–3e in vivo. We established CIA in 14–3–3eF/F (serve as WT) and 14–3–3eΔ/Δ mice, followed by i.p. injection of recombinant PGRN. The clinical arthritis score demonstrated that 14–3–3eΔ/Δ mice displayed increased severity of CIA compared with WT CIA. In addition, PGRN’s protective effects against inflammatory arthritis was compromised in 14–3–3eΔ/Δ mice (figure 1c), suggesting that 14–3–3e is critical downstream mediator of PGRN’s anti-inflammatory effects. In addition, FACS analysis showed that total numbers of F4/80 cells were not different in all WT and knockout CIA mice. However, analysis of CD45 +CD11b+cell population in spleen demonstrated a significant increase in mean fluorescence intensity (MFI) of iNOS and a significant decrease of CD206 +cells in PBS treated 14–3–3eΔ/Δ CIA mice as compared with PBS treated WT CIA mice; moreover, there was a significant decrease of iNOS MFI while a dramatic increase of CD206 +cells in PGRN-treated WT mice compared to that in PBS-treated mice. Further PGRN-mediated effects on macrophage polarisation was lost in 14–3–3eΔ/Δ CIA mice (Fig 1d, e). Cellectively, these results indicate that PGRN skews macrophage toward M2 polarisation to resolve inflammation and this effect depends on 14–3–3e. Conclusions Both in vitro and in vivo results indicate that 14–3–3e is a key molecule regulating macrophage polarisation which plays an important role in inflammatory arthritis, and it is an essential component for PGRN/TNFR2 mediated protective effect against inflammatory arthritis. Disclosure of Interest None declared

Background It has been reported that a disintegrin and metalloproteinase with thrombospondin motifs-12 (ADAMTS-12) is a susceptibility gene for rheumatoid arthritis (RA) development, and its level was significantly increased in RA patients. In addition, ADAMTS-12 was also reported to be required for normal inflammation. Objectives This study aims to determine the role of ADAMTS-12 and the underlying mechanisms in the pathogenesis of inflammatory arthritis. Methods Collagen-induced arthritis (CIA) was established in ADAMTS-12-/- mice and their control littermates to determine the role of ADAMTS-12 in vivo. Connective tissue growth factor (CTGF) deficient Raw264.7 were used to determine their functional interplays. Protein-protein interaction assays were performed to detect the interactions of ADAMTS-12 with CTGF Results ADAMTS-12-/- mice are more susceptible to collagen-induced arthritis. Accelerated disease onset, significant increase in the arthritis score and arthritis incidence, were observed in ADAMTS-12-/- mice (figure 1a). Histological analysis of whole ankle joints demonstrated a significant increase in synovitis, destruction of bone and cartilage loss in ADAMTS-12-/- mice. ELISA results indicated that ADAMTS-12-/- CIA mice exhibited enhanced release of pro-inflammatory and reduced secretion of anti-inflammatory cytokine. Collectively, these data demonstrate that ADAMTS-12-/- renders mice highly susceptible to CIA. ADAMTS-12 interacts with and cleaves CTGF, and ADAMTS-12-mediated signalling depends on CTGF during inflammation. It is known that CTGF plays a pro-inflammatory role in the pathogenesis of inflammatory arthritis. We co-transfected CTGF and ADAMTS-12 into 293 T cells and found ADAMTS-12 bound to (figure 1b) and digested CTGF (figure 1c). In vivo studies also demonstrated that CTGF was accumulated in the synovium of ADAMTS-12-/- CIA mice. To further determine whether CTGF is a critical regulator of ADAMTS-12 mediated signalling, we generated CTGF deficient Raw264.7. Overexpression of ADAMTS-12 and CTGF deficiency could decrease the activation of inflammatory signalling markers such as NFkb, p38 and JNK in response to IL-1β at a comparable level. More importantly, overexpression of ADAMTS-12 in CTGF deficient Raw264.7 failed to further inhibit the activation of these signal molecules as compared to CTGF deficient Raw264.7 (figure 1f). Taken together, these results suggest that CTGF is a critical regulator of ADAMTS-12 mediated signalling during inflammation. Blocking CTGF attenuates inflammatory arthritis in ADAMTS12-deficient CIA mice model. To determine whether the accelerated inflammation in ADAMTS-12-/- mice resulted from the accumulated CTGF, we administered CTGF antibody to ADAMTS-12-/- CIA model after disease onset. The arthritis score in ADAMTS-12 deficient mice was significantly reduced in presence of CTGF antibody (figure 1d). Moreover, histological analysis indicated CTGF abrogated further tissue destruction and inflammation (figure 1e). Conclusions ADAMTS-12-mediated regulation of inflammatory arthritis is probably through, at least in part, its interplay with CTGF and blockage of CTGF has been shown to be effective in treating inflammatory arthritis. Disclosure of Interest None declared

Objective It has been reported that ADAMTS-12 is a susceptibility gene for rheumatoid arthritis (RA) development, and its level is significantly increased in RA patients. In addition, ADAMTS-12 is reported to be required for inflammation in otherwise healthy subjects. This study was undertaken to determine the role of ADAMTS-12 and the underlying mechanisms in the pathogenesis of inflammatory arthritis. Methods The collagen-induced arthritis (CIA) model was established in ADAMTS-12-deficient mice and their control littermates to determine the role of ADAMTS-12 in vivo. Micro-computed tomography scanning was used to demonstrate the destruction of the ankle joint; histologic analysis illustrated synovitis, pannus formation, and bone and cartilage destruction; enzyme-linked immunosorbent assay was performed to measure serum levels of inflammatory cytokines; and protein-protein interaction assays were performed to detect the interactions of ADAMTS-12 and its various deletion mutants with connective tissue growth factor (CTGF). Results Deficiency of ADAMTS-12 led to accelerated inflammatory arthritis in the CIA mouse model. Loss of ADAMTS-12 caused enhanced osteoclastogenesis. In vitro and in vivo protein-protein interaction assays demonstrated that ADAMTS-12 bound and processed CTGF, a previously unrecognized substrate of ADAMTS-12. In addition, deletion of ADAMTS-12 enhanced, while overexpression of ADMATS-12 reduced, CTGF-mediated inflammation. Furthermore, ADAMTS-12 regulation of inflammation was largely lost in CTGF-deficient macrophages. Importantly, blocking of CTGF attenuated elevated inflammatory arthritis seen in the ADAMTS-12-deficient CIA mouse model. Conclusion This study provides evidence that ADAMTS-12 is a critical regulator of inflammatory arthritis and that this is mediated, at least in part, through control of CTGF turnover.

Background Atsttrin, an engineered protein composed of three tumor necrosis factor receptor (TNFR)-binding fragments of progranulin (PGRN), shows therapeutic effect in multiple murine models of inflammatory arthritis . Additionally, intra-articular delivery of PGRN protects against osteoarthritis (OA) progression. The purpose of this study is to determine whether Atsttrin also has therapeutic effects in OA and the molecular mechanisms involved. Methods Surgically induced and noninvasive rupture OA models were established in mouse and rat, respectively. Cartilage degradation and OA were evaluated using Safranin O staining, immunohistochemistry, and ELISA. Additionally, expressions of pain-related markers, degenerative factors, and anabolic and catabolic markers known to be involved in OA were analyzed. Furthermore, the anabolic and anti-catabolic effects and underlying mechanisms of Atsttrin were determined using in-vitro assays with primary chondrocytes. Results Herein, we found Atsttrin effectively prevented the accelerated OA phenotype associated with PGRN deficiency. Additionally, Atsttrin exhibited a preventative effect in OA by protecting articular cartilage and reducing OA-associated pain in both nonsurgically induced rat and surgically induced murine OA models. Mechanistic studies revealed that Atsttrin stimulated TNFR2-Akt-Erk1/2-dependent chondrocyte anabolism, while inhibiting TNFα/TNFR1-mediated inflammatory catabolism. Conclusions These findings not only provide new insights into the role of PGRN and its derived engineered protein Atsttrin in cartilage homeostasis as well as OA in vivo, but may also lead to new therapeutic alternatives for OA as well as other relative degenerative joint diseases. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1485-8) contains supplementary material, which is available to authorized users.

To evaluate the influence of deployment strategy on the mechanical interaction between braided stent and parent artery of intracranial aneurysm (the elasticity of the arterial wall is considered), finite-element analyses are carried out by referring to computational models of flow-diverter device and arterial wall. Two implantation strategies are used to virtually implant the braided stent into the ideal intracranial aneurysm model. One is the noncompacted implantation method, and the other is the implantation method of using push-pull technique. During the process of the implantation, the changes of the arterial shape around the aneurysm and the changes of the wall pressure at the contact area between the braided stent and the inner wall of the artery are analyzed. The results indicate that the average contact pressure in the area of low porosity is 57 mmHg using the push-pull technique, and the average contact pressure of the parent artery is 10.45 mmHg using the non-push-pull technique. The diameter of the parent artery at the aneurismal orifice increased about 0.2 mm when using the push-pull technique, so the elasticity of the vessel should be considered in the mechanical analysis of interaction between stent and vessel.

Progranulin (PGRN) restrains inflammation and is therapeutic against inflammatory arthritis; however, the underlying immunological mechanism remains unknown. In this study, we demonstrated that anti-inflammatory cytokine IL-10 was a critical mediator for PGRN-mediated anti-inflammation in collagen-induced arthritis by using PGRN and IL-10 genetically modified mouse models. IL-10 green fluorescent protein reporter mice revealed that regulatory T (Treg) cells were the predominant source of IL-10 in response to PGRN. In addition, PGRN-mediated expansion and activation of Treg cells, as well as IL-10 production, depends on JNK signaling, but not on known PGRN-activated ERK and PI3K pathways. Furthermore, microarray and chromatin immunoprecipitation sequencing screens led to the discovery of forkhead box protein O4 and signal transducer and activator of transcription 3 as the transcription factors required for PGRN induction of IL-10 in Treg cells. These findings define a previously unrecognized signaling pathway that underlies IL-10 production by PGRN in Treg cells and present new insights into the mechanisms by which PGRN resolves inflammation in inflammatory conditions and autoimmune diseases, particularly inflammatory arthritis.-Fu, W., Hu, W., Shi, L., Mundra, J. J. Xiao, G., Dustin, M. L., Liu, C. Foxo4- and Stat3-dependent IL-10 production by progranulin in regulatory T cells restrains inflammatory arthritis.

Computational fluid dynamics analyses were performed on three models which have a giant aneurysm with or without a stenosis. The first is a model with an aneurysm (no stenosis and no stent), the second is a model with a preaneurysm stenosis, and the third is a model with an aneurysm implanted with a stent. The increase in pressure in aneurismal sac caused by a 50% stenosis is about 10.3[Formula: see text]mmHg at peak systole (comparison between the second model and the first model). It must pay attention to the increase of the pressure for the patient which has an aneurysm accompanied by a stenosis when making the treatment plan. Otherwise, it may cause the aneurysm rupture.

There is still a considerable lack of quantitative information concerning the effects of stent structures on blood flow in an aneurismal cavity. In this paper, five virtual stents with different structures and wire cross-sections were designed for incorporation into the same patient-specific aneurysm model. Computational fluid dynamics simulations were performed so as to study how these five types of stents modified hemodynamic parameters. Numerical results demonstrated that the mean flow rate in the aneurismal cavity decreased the most in the model that used a stent with a rectangular wire cross-section, and that the wall shear stresses at the dome and neck of the aneurysm decreased more in models that used a stent with a circular wire cross-section or a spiral stent with a rectangular wire cross-section compared to other models. In addition, the wall pressure on the aneurysm increased slightly after implantation of the stent in all five models. This result differs from that previously published, and may help guide the design and assist clinicians in selecting an appropriate stent for treating cerebral aneurysms.

The objective of this study is to investigate the hemodynamics in patient-specific internal carotid aneurysm and discuss the reason for rupture of aneurysm. A 3-Dimensional pulsatile blood flow in internal carotid with a sidewall aneurysm was studied numerically with the average Reynolds number of 704. Patient-specific model whose parent artery has a large "S" bending and a sidewall aneurysm was constructed from CT data. Unsteady, incompressible, 3-Dimensional Navier-Stokes equations were employed to solve the flow field. The temporal distributions of hemodynamic variables during the cardiac cycle such as streamlines, wall pressure and wall shear stress (WSS) in the arteries and aneurysm were analyzed. From streamlines it can be found that there is an obvious vortex flow in aneurismal cavity in a cardiac cycle. The type of this vortex flow is not changed in a cardiac cycle. As far as Wall Shear Stress, there is a region in aneurismal neck where the value of WSS is relatively high. Growth and rupture mechanism of internal carotid aneurysm in patient can be analyzed based on patient-specific model and hemodynamics simulation.

An intracranial aneurysm (IA) is a pathological dilatation of the cerebral artery wall. Blood flow and pressure inside IA are not steady. Interaction between blood flow and vessel wall reveals stress and deformation of vessel wall in vivo. It also provides more true and reliable information about blood flow. So analysis of Fluid Structure Interaction (FSI) is favor of proper explanation for formation and development of aneuris-mal disease. Patient-specific model whose parent artery has a large “S” bending and a side wall aneurysm was constructed from CT data. Pulsatile calculation of FSI for this constructed model was carried out. From streamlines it can be found that there is an obvious vortex flow in aneurismal cavity in a cardiac cycle. The type of this vortex flow is not changed in a cardiac cycle. As far as Wall Shear Stress (WSS), there is a region in aneurismal neck where the value of WSS is relatively high. At 0.27s in a cardiac cycle, deformation of the vessel wall is the biggest. There are two regions in aneurismal dome where the value of Von Mises Stress is the locally biggest.

Endovascular stents with different porosities and wire cross-section shapes may create different effects on the hemodynamics of aneurysm treated with interventional therapy because stents with different wire cross-section shapes induce different flow resistances through the stent strut. In order to analyze the flow resistance of the new stent with triangular cross-section by numerical simulation method, and to provide a reference basis for the structural design and optimization of endovascular stent, four kinds of models of the triangular cross-section bare stent were constructed using SoildWorks 2007 software. Numerical simulations of steady and transient blood flows in the four models were performed respectively according to CFD method using finite element software ANSYS 11. Hemodynamics data in the four models were collected, such as the flow patterns, the distribution of pressure and the flow resistance. The results show that the stent with triangular wire cross-section can produce large resistance of blood inflow to aneurysm and small resistance of outflow from aneurysm. Thus, outflow is easy and inflow is difficult. Thereby blood perfusion and flow of aneurysm cavity is restrained, and the pressure of aneurysm cavity is reduced, which plays certain effect on the intervention treatment of aneurysm. This result provides some instructions for the design of stent structure.

An intracranial aneurysm (IA) is a pathological dilatation of the cerebral artery wall. In clinical practice it is currently widely accepted that maximum diameter of IA is an indicator for patient whether to treat or not. But studies have demonstrated that maximum diameter is not a reliable determinant of IA rupture. According to the theory of strength, if the stress value exceeds the strength limit of material, it will result in failure. So wall stress may be a better indicator to predict aneurismal rupture (failure). Study about wall stress calculated from solid stress model using static pressure has been performed. But blood flow and pressure inside IA are not steady. The dynamic interaction between the unsteady flow and wall may influence the distribution and magnitude of wall stress. The objective of the present study was to compare static and dynamic wall stress analysis of patient specific IA. Patient-specific model of cerebral aneurysm whose host artery has large bending was created from CT data. Simulations about fluid structure interaction model and static structural model were carried out respectively. Commercial software Ansys 11 was used for simulation. The results demonstrated that FSI can change local wall stresses slightly. However, as far as the peak wall stress is concerned, the change of wall stress is negligible. Therefore static structural simulation can be used to predict rupture risk of aneurysm if wall stress was used as an indicator of aneurismal rupture and computational cost can be reduced greatly.

Tributyltin (TBT) is one of the environmental pollutants, which is mostly accumulated in marine animals. The toxic effects of TBT have been extensively documented in several types of cells, but the molecular mechanisms responsible for TBT-induced cell damage are still not fully elucidated. The present study was undertaken to evaluate the apoptotic related biochemical changes in human amnion cells induced by TBT. After cells were exposed to TBT at the concentrations of 1–4 μM for 2 h, the results suggested that TBT could induce an early and typical apoptosis, moreover caspase-3, the modifications of cytoskeletal structure and the Bcl-2 family were involved in this process. The results will deepen our understanding about the toxic mechanism of TBT on human amnion cells.