Preclinical Evaluation of a Non-Customized Modular Inner Branched Stent Graft for Total Endovascular Aortic Arch Repair in a Porcine Model.

OBJECTIVES: The aim of this study was to evaluate the feasibility and safety of a non-customized modular inner branched stent graft for total endovascular aortic arch repair in a porcine model. METHODS: The modular inner branched stent graft system with a split main body design included 1 proximal main component, 1 distal main component, and 1 branched covered stent. The gutter in the proximal main component was sealed with sutured membrane. Fatigue testing was performed to evaluate the durability of the stent graft. Fifteen pigs were used in this study. In each pig, a stent graft was delivered and deployed to the aortic arch through the femoral arterial access and right carotid arterial access. Angiography and computed tomography angiography were used to evaluate the morphological features before euthanasia. After euthanasia, the implanted device, surrounding tissue, and major organs were harvested for gross and histological examination. RESULTS: There were no collapses and no stent graft fractures detected after fatigue testing. The technical success rate was 14/15, and the incidence of major adverse cardiovascular events was 2/15. Angiography performed at the end of follow-up revealed no endoleaks and no device migration. Histological examination demonstrated excellent biocompatibility of the stent graft. CONCLUSIONS: The non-customized modular inner branched stent graft system is safe and feasible for the endovascular reconstruction of the aortic arch in a porcine model.

Screening of host gut-derived probiotics and effects of feeding probiotics on growth, immunity, and antioxidant enzyme activity of hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂).

In recent years, the widespread use of antibiotics in intensive grouper mariculture has resulted in the ineffectiveness of antibiotic treatment, leading to an increasing incidence of diseases caused by bacteria, viruses, and parasites, causing serious economic losses. Hence, it is crucial to develop alternative strategies to antibiotics for healthy and sustainable development of the mariculture industry. Here, we aimed to screen host gut-derived probiotics and evaluate its effects on growth and immunity of grouper. In this study, 43 bacterial strains were isolated from the intestine of the hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂), and a potential probiotic strain G1-26, which can efficiently secrete amylase, protease, and lipase, was obtained using different screening mediums. Based on 16S rDNA sequencing, the potential probiotic strain G1-26 was identified as Vibrio fluvialis. The results of a biological characteristic evaluation showed that V. fluvialis G1-26 could grow at 25-45 °C, pH 5.5-7.5, salinity 10-40, and bile salt concentration 0-0.030%, and produce amylase, lipase, and protease under different culture conditions. Additionally, V. fluvialis G1-26 is sensitive to many antibiotics and does not exhibit aquatic biotoxicity. Subsequently, hybrid groupers were fed diets containing V. fluvialis G1-26 at different concentrations (0, 106, 108, and 1010 CFU/g) for 60 d. The results showed that V. fluvialis G1-26 at 108 CFU/g did not significantly affect the growth performance of the hybrid grouper (P > 0.05). V. fluvialis G1-26 supplementation at 108 and 1010 CFU/g significantly promoted the relative expression of immune-related genes in hybrid groupers (TLR3, TLR5, IL-1ß, IL-8, IL-10, CTL, LysC, TNF-2, and MHC-2) and improved the activities of alkaline phosphatase, acid phosphatase, total superoxide dismutase, and total protein in the liver. In conclusion, V. fluvialis G1-26, a potential probiotic strain isolated from the intestine of the hybrid grouper, can be used as an effective immunopotentiator at an optimal dose of 108 CFU/g diet. Our results provide a scientific basis for the development and utilization of probiotics in the grouper mariculture industry.

[Effect of soil moisture on efficacy to eliminate dampness and relieve jaundice and flavonoid content of Sedum sarmentosum].

The growth environment of medicinal plants plays an important role in the formation of their medicinal quality. However, there is a lack of combined analysis studying the close relationship between the growth environment, chemical components, and related biological activities of medicinal plants. Therefore, this study investigated the effect of different soil moisture treatments on the efficacy to eliminate dampness and relieve jaundice and the flavonoid content of Sedum sarmentosum, and explored their correlation. The flavonoid content in the decoction of S. sarmentosum growing under field conditions with soil moisture levels of 35%-40%(T1), 55%-60%(T2), 75%-80%(T3), and 95%-100%(T4) was compared. The effects of these treatments on liver function parameters, liver inflammation, and oxidative damage in mice with dampness-heat jaundice were evaluated, and the correlation between pharmacological indicators and flavonoid content was analyzed. The results showed that the total flavonoid and total phenolic acid content in the decoction of S. sarmentosum were highest in the T1 treatment, followed by the T3 treatment. The content of quercetin, kaempferol, and isorhamnetin was highest in the T2, T1, and T3 treatments, respectively. Among the different moisture treatments, the T3 group of S. sarmentosum effectively reduced the levels of serum ALT, AKP, TBIL, DBIL, TBA, as well as hepatic TNF-α and IL-6 in mice with jaundice, followed by T2 treatment, especially in reducing AST level. The T4 treatment had the poorest effect. Correlation analysis showed a significant negative correlation between AST, ALT, AKP levels in mice and the total content of quercetin and the three flavonoids. MDA showed a significant negative correlation with the total flavonoid content and kaempferol. TNF-α exhibited a significant negative correlation with the content of isorhamnetin. In conclusion, S. sarmentosum growing under field conditions with a soil moisture level of 75%-80% exhibited the best efficacy to eliminate dampness and relieve jaundice. This study provides insights for optimizing the cultivation mode of medicinal plants guided by pharmacological experiments.

Splenic Arteriovenous Fistula Accompanied by Splenic Artery Aneurysm Associated with Acute-onset Portal Hypertension and Gastrointestinal Bleeding: Case Report and Literature Review.

Splenic arteriovenous fistula is an uncommon aetiology of portal hypertension, which has definitive treatment effectiveness and good prognosis. We report a case of portal hypertension and gastrointestinal bleeding in the absence of hepatic parenchymal disease in a 50 year-old woman with multiple pregnancies. Abdominal computed tomography and transabdominal arteriography recorded the presence of tortuous and aneurysmal splenic arteries and the premature filling of enlarged splenic veins, which are highly suggestive of splenic arteriovenous fistula. The above vascular abnormalities were successfully treated by transcatheter embolization. No recurrence or other complications were observed. In addition, a literature review concerning splenic arteriovenous fistula published in recent 30 years was performed to further our understanding of the management strategy on this entity.

Integrate analysis of the promote function of Cell division cycle-associated protein family to pancreatic adenocarcinoma.

Background: The cell division cycle-associated (CDCA) protein family plays a pivotal role in the regulation of the cell cycle during tumorigenesis and predicts the prognosis of tumors, but an analysis of these proteins in pancreatic adenocarcinoma (PAAD) is still lacking. Methods: Oncomine and GEPIA were used to observe the expression and prognostic value of eight CDCAs in pan-cancer. Univariate Cox analysis of single CDCAs and multivariate Cox analysis of all eight CDCAs were performed to evaluate the integrated prognostic value of CDCAs, and the results are displayed as hazard ratios (HRs) and 95% confidence intervals (95% CIs). K-M plots and receiver operating characteristics curves were used to display the predicted function and accuracy of CDCAs to determine the risk score. Annotation of CDCA-related genes, gene sets enrichment analysis (GSEA) and gene sets variation analysis (GSVA) were performed to reveal the CDCAs that impact biological processes. Results: CDCAs expression in most tumors is higher than that in normal tissues and is associated with a poor prognosis. Regarding PAAD, increased CDCA expression along with advanced PAAD tumor stage, NUF2, CDCA2, CDCA3, CDCA4 and CDCA5 expression are risk factors for poor prognosis, while CBX2 expression is a protective factor (P < 0.05). The integrated prognostic value of CDCAs in PAAD patients was validated by SurvExpress in the TCGA-PAAD cohort (P < 0.001, HR = 2.16, 95% CI = 1.41-3.3) and the ICGC-PACA cohort (P < 0.001, HR = 2.56, 95% CI = 1.73-3.79). Genetic alteration and DNA methylation of CDCAs might not affect the prognosis of PAAD patients. After comparing high- and low-risk groups separated by CDCA risk scores, the activated pathways were revealed and included the cell cycle, DNA repair, P53, MYC-targets, E2F-targets and PI3K pathways. Conclusion: CDCAs can predict the OS prognosis of PAAD patients. The cell cycle, DNA repair, E2F, P53 and PI3K signaling pathways, in which CDCAs are involved, impact the tumorigenesis of PAAD.

Treatment Strategies and Outcomes of Symptomatic Spontaneous Isolated Superior Mesenteric Artery Dissection: A Systematic Review and Meta-analysis.

PURPOSE: To analyze the published treatment experience with symptomatic spontaneous isolated superior mesenteric artery dissection (SISMAD). METHODS: A literature search of the PubMed and Cochrane databases was conducted for articles on symptomatic SISMAD published in English from January 2007 to January 2018. Case series reporting on both treatment modalities and outcomes were included, while those on traumatic or iatrogenic SMA dissection or SMA dissection accompanied by aortic or other visceral artery dissection were excluded. Overall event rates for treated symptomatic SISMAD were calculated using pooled analyses. The rate of initial conservative treatment, the success rate, the rate of conversion to intervention, and the failure rate in patients with vs without antithrombotic therapy were calculated for each study and compared using a meta-analysis of proportions. RESULTS: The 25 articles selected encompassed 616 SISMAD cases, of which 514 were symptomatic cases eligible for the analysis. Among the latter, initial treatment consisted of conservative therapy in 447 (87.0%) patients and surgical interventions in 67 (13.0%) patients [45 (8.7%) endovascular procedures and 22 (4.3%) open surgeries]. Among conservative cases, 238 (53.2%) received antithrombotic therapy while 172 (38.5%) did not; 50 (11.2%) cases were converted to intervention [42 (84%) endovascular]. Conservative treatment was initially used in 85.2% of pooled cases with an 84.7% success rate, a 14.3% rate of conversion to intervention, and conservative treatment failure rates of 17.8% and 10.1% in patients treated with vs without antithrombotic therapy, respectively (p=0.103). CONCLUSION: Conservative treatment appeared safe and effective in >80% of symptomatic SISMAD cases, without apparent benefit for antithrombotic agent use. Initial or secondary intervention was more often endovascular, with favorable success rates and short-term outcomes. Large, prospective randomized trials with long-term follow-up are warranted on the treatment for symptomatic SISMAD.

Research advances on microplastics contamination in terrestrial geoenvironment: A review.

The contamination of microplastics in terrestrial geoenvironment (CMTG) is widespread and severe and has, received considerable attention. However, studies on CMTG are in their initial stages. The literature on CMTG published in the past decade was analyzed through bibliometric analysis, such as the annual publications, countries with the highest contributions, prolific authors, and author keywords. The sources, compositions, migrations and environmental impacts of CMTG are summarized, and possible future directions are proposed. This study analyzed the annual publications, countries with the highest contributions, prolific authors, and author keywords related to microplastics. The results demonstrated that 15,306 articles were published between 2014 and 2023. China is the leading country in terms of the total number of publications. The main sources of CMTG include landfills, agricultural non-point sources, sewage treatment systems and transportation systems. The composition of the CMTG exhibits significantly temporal and spatial variability from different sources. The migration paths of the CMTG were within the soil, groundwater seepage and wind transportation of suspended particles. Microplastics increase soil cohesion, decrease porosity, reduce pore scale, decrease air circulation, and increase water retention capacity, and the exudation of highly water-soluble additives in microplastics can cause secondary contamination of geological entities. Microplastics have an adverse effect on plant growth, animal digestion, microbial activity, energy and lipid metabolism, oxidative stress, and respiratory diseases in humans. It is recommended to develop more efficient and convenient quantitative testing methods for microplastics, formulate globally harmonized testing and evaluation standards, include microplastic testing in testing programs for contaminated soils, and develop efficient methods for the remediation of microplastic contaminated geological bodies.

Action mechanisms and characteristics of miRNAs to regulate virus replication.

MicroRNAs (miRNAs) have the potential to be explored as antiviral products. It is known that miRNAs have different kinds of target mRNAs and different target sites in mRNAs, and that the action-modes of miRNAs at different target sites may be different. But there is no evidence demonstrating the significance of the differences for the regulation of viruses by miRNAs, which might be crucial for the exploration of miRNA-based antiviral products. Here the experimental studies about the antiviral effects of miRNAs, with validated target mRNAs and target sites in the mRNAs, were systematically collected, based on which the mechanisms whereby miRNAs regulated virus replication were systematically reviewed. And miRNAs' down-regulation rates on target mRNAs and antiviral rates were compared among the miRNAs with different target sites, to analyze the characteristics of action-modes of miRNAs at different target sites during virus replication.

Evidence of Cross-Kingdom Gene Regulation by Plant MicroRNAs and Possible Reasons for Inconsistencies.

The debate on whether cross-kingdom gene regulation by orally acquired plant miRNAs is possible has been ongoing for nearly 10 years without a conclusive answer. In this study, we categorized plant miRNAs into different groups, namely, extracellular vesicle (EV)-borne plant miRNAs, extracted plant miRNAs, herbal decoction-borne plant miRNAs, synthetic plant miRNA mimics, and plant tissue/juice-borne plant miRNAs. This categorization aimed to simplify the analysis and address the question more specifically. Our evidence suggests that EV-borne plant miRNAs, extracted plant miRNAs, herbal decoction-borne plant miRNAs, and synthetic plant miRNA mimics consistently facilitate cross-kingdom gene regulation. However, the results regarding the cross-kingdom gene regulation by plant tissue- and juice-borne plant miRNAs are inconclusive. This inconsistency may be due to variations in study methods, a low absorption rate of miRNAs and the selective absorption of plant miRNAs in the gastrointestinal tract. Overall, it is deduced that cross-kingdom gene regulation by orally acquired plant miRNAs can occur under certain circumstances, depending on factors such as the types of plant miRNAs, the delivery mechanism, and their concentrations in the plant.

Analysis of Postoperative Remodeling Characteristics after Modular Inner Branched Stent-Graft Treatment of Aortic Arch Pathologies Using Computational Fluid Dynamics.

The modular inner branched stent-graft (MIBSG), a novel interventional therapy, has demonstrated good effects in the endovascular treatment of aortic arch pathologies, especially those involving the supra-aortic branches. Nevertheless, the long-term efficacy of the MIBSG and in-depth quantitative evaluation of postoperative outcomes remain to be examined. Moreover, the regularity of postoperative vascular remodeling induced by MIBSG implantation has yet to be explored. To address these questions, we constructed four models (normal, preoperative, 1 week postoperative, and 6 months postoperative) based on a single patient case to perform computational fluid dynamics simulations. The morphological and hemodynamic characteristics, including the velocity profile, flow rate distribution, and hemodynamic parameter distribution (wall shear stress and its derivative parameters), were investigated. After MIBSG implantation, the morphology of the supra-aortic branches changed significantly, and the branch point moved forward to the proximal ascending aorta. Moreover, the curvature radius of the aortic arch axis continued to change. These changes in morphology altered the characteristics of the flow field and wall shear stress distribution. As a result, the local forces exerted on the vessel wall by the blood led to vessel remodeling. This study provides insight into the vascular remodeling process after MIBSG implantation, which occurs as a result of the interplay between vascular morphological characteristics and blood flow characteristics.

Nitrogen-doped magnetic porous carbon material from low-cost anion-exchange resin as an efficient adsorbent for tetracyclines in water.

In this work, nitrogen-doped magnetic porous carbon material (N-MPC) was prepared through the high-temperature calcination of low-cost [Fe(CN)6]3--loaded anion-exchange resin, which was experimentally demonstrated to have significant adsorption performance for tetracycline (TC) in water. The N-MPC adsorbent with a large specific surface area (781.1 m2 g-1) was able to maintain excellent performance in a wide pH range from 4 to 10 or in high ionic strength solution. The adsorption of TC on N-MPC was found to be more consistent with the pseudo-second-order model and Langmuir adsorption model, and the maximum adsorption capacity (qm, cal) was calculated to be 603.4 mg g-1. As a recoverable magnetic adsorbent, the N-MPC remained a TC removal rate higher than 70% after four adsorption cycles. The adsorption mechanism was speculated on the basis of characterizations, where pore filling, hydrogen bonding interaction, and π-π electron donor-acceptor (EDA) interaction were crucial adsorption mechanisms. A variety of antibiotics were selected for adsorption, and excellent performance was found especially for TCs, indicating that the N-MPC can be used for the efficient removal of TCs from water.

CRISPR/Cas12a combined with RPA for detection of T. gondii in mouse whole blood.

BACKGROUND: Toxoplasma gondii is an opportunistic protozoan that is ubiquitous in humans and animals. It can invade any human organ and cause severe diseases, including toxoplasma ophthalmopathy, meningoencephalitis, and liver necrosis. Porcine toxoplasmosis is prevalent in China. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and Cas (CRISPR-Associated Protein) systems are widely used for gene editing and pathogen detection. CRISPR-based diagnostics are molecular assays that have been developed to detect parasites with high sensitivity and specificity. METHODS: This study aimed to establish a combined CRISPR/Cas12a and RPA rapid detection method for T. gondii by targeting the B1 gene and 529 bp repeat element (529 RE). The detection results could be visualized by the fluorescence or lateral flow strips (LFS). The sensitivity and specificity of the method were evaluated, and T. gondii-infected mouse blood was used for detection. RESULTS: The results indicated that the established method for T. gondii detection was satisfactory, with a detection limit of 1.5 cp/µl for the two loci. Moreover, the B1 gene could detect 1 tachyzoite per reaction, and the 529 RE could detect 0.1 tachyzoite per reaction, consistently with the highly sensitive nested polymerase chain reaction (PCR) results. The method was suitable for strains, including RH, and did not cross-react with other protozoa DNA with similar habits. The T. gondii-infected mouse blood samples were all positive for T. gondii at 1, 3, and 5 days post infection (dpi). CONCLUSIONS: This study established a rapid, sensitive, and time-saving DNA detection method for T. gondii that has the potential to be an alternative tool for T. gondii detection in the field.

A phenomenological, intersectional understanding of coping with ageism and racism among older adults.

The aim of this qualitative, phenomenological study was to understand how older adults cope with experiences of ageism and racism through an intersectional lens. Twenty adults 60+ residing in the U.S. Mountain West who identified as Black, Hispanic/Latino(a), Asian-American/Pacific Islander, Indigenous, or White participated individually in a one-hour, semi-structured interview. A team of five coders engaged in an inductive coding process through independent coding followed by critical discussion. Peer debriefing enhanced credibility. Nine themes were organized by three umbrella categories: Coping with ageism: 1) distancing via self-determination/defying stereotypes, 2) distancing by helping others; Coping with racism: 3) resistance, 4) exhaustion; Coping with both ageism and racism: 5) increased awareness through aging, 6) healthy lifestyle, 7) education, 8) acceptance/ 'let it go', and 9) avoidance. Novel findings include how older adults may cope with ageism and racism via increased awareness through aging and with ageism specifically by helping peer older adults, although instances of internalized ageism were noted and discussed. The themes exemplify problem-focused (e.g., helping others) and emotion-focused (acceptance), as well as individual (e.g., self-determination) and collective (e.g., resistance) coping strategies. This study can serve as a resource for practitioners in applying a more nuanced understanding of the ways older adults cope with ageism and racism in later life.

Gb3-Coated Bovine Milk Exosomes as a Practical Neutralizer for Shiga Toxin.

Shiga toxin (Stx) is associated with foodborne infections of some Shigella spp. and Shiga toxin-producing Escherichia coli (STEC), leading to life-threatening hemolytic uremic syndrome (HUS). Target-specific therapeutics against HUS are currently unavailable in clinical practice. Herein, we reported the construction and in vitro characterization of Gb3-coated bovine milk exosomes (Gb3-mExo) as a multivalent Shiga toxin neutralizer, utilizing the natural advantages of milk exosomes (mExo) in drug delivery and multivalent interactions between Stx and its receptor Gb3. Gb3-mExo constructs were achieved by conjugating mExo with the Gb3 derivatives containing stearic acid-derived lipid tail, which was prepared through an efficient chemoenzymatic approach. The constructs were able to potently neutralize the binding of the B subunit of Stx2 (Stx2B) to receptor Gb3 immobilized on the plate or expressed on model cells. General safety of the constructs was evidenced by the cytotoxicity analysis and hemolysis assay. In addition to the excellent stability under conventional storage and handling conditions, the construct can also retain most of its neutralization potency under gastrointestinal pH extremes, showing the potential for oral administration. Considering the natural availability and excellent biocompatibility of mExo, Gb3-mExo conjugates should prove to be a practical prophylactic and therapeutic for the Shiga toxin-related infections.

Salicylic Acid Modulates the Osmotic System and Photosynthesis Rate to Enhance the Drought Tolerance of Toona ciliata.

Toona ciliata M. Roem. is a valuable and fast-growing timber species which is found in subtropical regions; however, drought severely affects its growth and physiology. Although the exogenous application of salicylic acid (SA) has been proven to enhance plant drought tolerance by regulating the osmotic system and photosynthesis rate, the physiological processes involved in the regulation of drought tolerance by SA in various plants differ. Therefore, drought mitigation techniques tailored for T. ciliata should be explored or developed for the sustainable development of the timber industry. We selected 2-year-old T. ciliata seedlings for a potting experiment, set the soil moisture at 45%, and subjected some of the T. ciliata seedlings to a moderate drought (MD) treatment; to others, 0.5 mmol/L exogenous SA (MD + SA) was applied as a mitigation test, and we also conducted a control using a normal water supply at 70% soil moisture (CK). Our aim was to investigate the mitigating effects of exogenous SA on the growth condition, osmotic system, and photosynthesis rate of T. ciliata under drought stress conditions. OPLS-VIP was used to analyze the main physiological factors that enable exogenous SA to alleviate drought-induced injury in T. ciliata. The results indicated that exogenous SA application increased the growth of the ground diameter, plant height, and leaf blades and enhanced the drought tolerance of the T. ciliata seedlings by maintaining the balance of their osmotic systems, improving their gas exchange parameters, and restoring the activity of their PSII reaction centers. The seven major physiological factors that enabled exogenous SA to mitigate drought-induced injury in the T. ciliata seedlings were the soluble proteins (Sp), net photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (Gs), stomatal opening window (Sow), activity of the photosystem II reaction center (ΦPSII), and electron transfer rate (ETR). Of these, Sp was the most dominant factor. There was a synergistic effect between the osmotic system and the photosynthetic regulation of drought injury in the T. ciliata seedlings. Overall, our study confirms that exogenous SA enhances the drought tolerance of T. ciliata by modulating the osmotic system and photosynthesis rate.

A Phenomenological Understanding of the Intersection-ality of Ageism and Racism Among Older Adults: Individual-Level Experiences.

OBJECTIVES: Ageism is a prevalent, insidious social justice issue that has harmful effects on the health of older adults. Preliminary literature explores the intersectionality of ageism with sexism, ableism, and ageism experienced among LGBTQ+ older adults. Yet, the intersectionality of ageism with racism remains largely absent from the literature. Therefore, this study explores the lived experience of the intersectionality of ageism and racism among older adults. METHODS: This qualitative study applied a phenomenological approach. Twenty participants 60+ years of age (M = 69, standard deviation = 8.84) in the U.S. Mountain West identifying as Black, Latino(a), Asian-American/Pacific Islander, Indigenous, or White engaged in a 1-hr interview between February and July 2021. A 3-cycle coding process applied constant comparison methods. Five coders independently coded interviews, engaging in critical discussion to resolve disagreements. An audit trail, member checking, and peer debriefing enhanced credibility. RESULTS: This study focuses on individual-level experiences exemplified by 3 umbrella themes and 7 subthemes. The subthemes are (a) compounding oppression, (b) intersection of disparities, (c) White privilege, (d) racism and ageism: being tokenized or ignored, (e) ageism and racism: unspoken bias, (f) racism versus ageism: overt or covert? and (g) racism versus ageism: differentiated or ubiquitous? DISCUSSION: The findings indicate how ageism may be racialized through stereotypes related to mental (in)capability. Practitioners can apply the findings to enhance support for older adults by designing interventions aimed at reducing racialized ageist stereotypes and increasing collaboration through education across anti-ageism/anti-racism initiatives. Future research should focus on the impacts of the intersectionality of ageism and racism on specific health outcomes in addition to structural-level interventions.

Impact of Cross-Limb Stent-Graft Configuration on Hemodynamics in Abdominal Aortic Aneurysm Interventional Therapy.

PURPOSE: The cross-limb (CL) technique is a commonly used endovascular treatment for addressing unfavorable anatomical features in patients with abdominal aortic aneurysm (AAA). The configuration of CL stent-graft plays a critical role in determining the postoperative hemodynamic properties and physiological behaviors, which ultimately impact the efficacy and safety of endovascular AAA treatment. This study aims to investigate the relationship between hemodynamics and CL stent-graft configuration from a hemodynamic perspective. METHODS: Five distinct geometric models of cross-limb (CL) stent-graft configurations were constructed by optimizing the real clinical computed tomography angiography (CTA) data. These models varied in main body lengths and cross angles and were used to perform numerical simulations to analyze various hemodynamic parameters. Flow pattern, distribution of wall shear stress (WSS)-related parameters, localized normalized helicity (LNH), pressure drop, and the displacement force of all models were examined in this paper. RESULTS: In patient-specific cases, helical flow and WSS increase with the main body. However, it also generated secondary flow in localized areas, leading to increased oscillation in the WSS direction. Notably, increasing the stent graft's main body length or decreasing the cross angle reduced the displacement force exerted on the stent-graft. Reducing the cross angle did not significantly alter the hemodynamic characteristics. CONCLUSION: In the clinical practice of CL deployment, it is crucial to carefully consider the stent-graft configuration and the patient specific to achieve optimal postoperative outcomes. This study provides valuable insights for guiding stent selection and treatment planning in patients with abdominal aortic aneurysm undergoing CL techniques, from a hemodynamic perspective.

The heparan sulfate mimetic Muparfostat aggravates steatohepatitis in obese mice due to its binding affinity to lipoprotein lipase.

BACKGROUND AND PURPOSE: Heparanase is the only confirmed endoglycosidase that cleaves heparan sulfate (HS), a ubiquitous glycosaminoglycan with various essential roles in multiple pathological processes. Thus, the development of heparanase inhibitors has become an attractive strategy for drug discovery, especially in tumour therapy, in which HS mimetics are the most promising compounds. The various biological effects of heparanase also suggest a role for HS mimetics in many non-cancer indications, such as type 1 diabetes. However, the potential benefits of HS mimetics in obesity-related type 2 diabetes have not been elucidated. EXPERIMENTAL APPROACH: In this study, we investigated muparfostat (PI-88), a developed HS mimetic currently enrolled in Phase III clinical trials, in obese mouse models and in vitro cultured murine hepatocytes. KEY RESULTS: Daily administration of muparfostat for 4 weeks caused hyperlipidaemia and aggravated hepatic steatosis in obese mice models, but not in lean animals. In cultured hepatocytes, muparfostat did not alter lipid accumulation. Acute tests suggested that muparfostat binds to lipoprotein lipase in competition with HS on vascular endothelial cell surfaces, thereby reducing the degradation of circulating triglycerides by lipoprotein lipase and subsequent uptake of fatty acids into vascular endothelial cells and causing hyperlipidaemia. This hyperlipidaemia aggravates hepatic steatosis and causes liver injury in muparfostat-treated obese mice. CONCLUSIONS AND IMPLICATIONS: The binding activity of HS mimetics to lipoprotein lipase should be investigated as an additional pharmacological effect during heparanase inhibitor drug discovery. This study also provides novel evidence for an increased risk of drug-induced liver injury in obese individuals.

Endovascular chimney technique of aortic arch pathologies: a systematic review.

BACKGROUND: The aim of this review was to determine the safety and efficacy of endovascular chimney technique for aortic arch pathologies by performing a systematic and pooled analysis of the relevant literature. METHODS: Electronic searches were performed in database Medline between 1994 and 2011 to identify studies on endovascular chimney technique for aortic arch pathology. The extracted variables and outcomes were synthesized through pooled analyses. RESULTS: Eight articles with 51 patients who underwent endovascular chimney technique for aortic arch pathologies met the inclusion criteria. Chimney grafts were deployed in innominate (n = 11), left common carotid (n = 32), and left subclavian (n = 12) arteries. Single-stent chimney in the deployed artery was used in 37 patients, whereas double-stent chimney was utilized in 14 patients. The overall technical success rate was 90.2%. The overall perioperative mortality and morbidity were 5.9% and 13.7%, respectively. The stroke rate was 7.8%, and the fatal stroke rate accounted for 50%. The rates of primary early endoleaks and type-Ia endoleaks were 21.6% and 11.8%, respectively. The overall late mortality and morbidity were 4.4% and 15.5%, respectively. Of 5 late endoleaks, no secondary type-Ia endoleak occurred. No studies had adequate follow-up to reliably evaluate the long-time durability. CONCLUSIONS: Endovascular chimney technique is technically feasible with the high initial technical success rate and relatively favorable rates of perioperative outcomes for aortic arch pathologies. However, further establishment of the role of endovascular chimney necessitates the accumulation of more cases and comparative study with other management as well as prolonged follow-up.