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1.
Food Chem ; 459: 140255, 2024 Jun 27.
Article de Anglais | MEDLINE | ID: mdl-38986201

RÉSUMÉ

This study investigated the effects of two forms of curdlan, namely curdlan thermoreversibility (CT) and curdlan powder (CP), on in vitro digestion and viscoelastic properties of myofibrillar protein (MP). As the level of curdlan (0.1-0.5%) increased, pepsin digestibility and pancreatin digestibility significantly decreased, active sulfhydryl group also decreased, while surface hydrophobicity and total sulfhydryl groups increased. Meanwhile, curdlan enhanced the secondary and tertiary structures of MP. As the pepsin digest, α-helix gradually transformed into random coil. Furthermore, the viscosity, storage modulus (G") and loss modulus (G') increased with the CT or CP addition. After in vitro digestion, the viscoelasticity significantly decreased with a dose-response. Molecular dynamics simulations showed hydrogen bond formation (2.86 on average) between MP and curdlan contributing to reduced radius of gyration and solvent accessible surface area. Overall, this study highlighted curdlan as a promising ingredient to modulate structural properties and digestibility of MP, especially in pre-hydrated (CT) groups.

2.
JOR Spine ; 7(3): e1357, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39011365

RÉSUMÉ

Backgrounds: The ossification of the ligamentum flavum (OLF) is one of the major causes of thoracic myelopathy. Previous studies indicated there might be a potential link between metabolic disorder and pathogenesis of OLF. The aim of this study was to determine the potential role of metabolic disorder in the pathogenesis of OLF using the strict bioinformatic workflow for metabolism-related genes and experimental validation. Methods: A series of bioinformatic approaches based on metabolism-related genes were conducted to compare the metabolism score between OLF tissues and normal ligamentum flavum (LF) tissues using the single sample gene set enrichment analysis. The OLF-related and metabolism-related differentially expressed genes (OMDEGs) were screened out, and the biological functions of OMDEGs were explored, including the Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and protein-protein interaction. The competing endogenous RNA (ceRNA) network based on pairs of miRNA-hub OMDEGs was constructed. The correlation analysis was conducted to explore the potential relationship between metabolic disorder and immunity abnormality in OLF. In the end, the cell experiments were performed to validate the roles of GBE1 and TNF-α in the osteogenic differentiation of LF cells. Results: There was a significant difference of metabolism score between OLF tissues and normal LF tissues. Forty-nine OMDEGs were screened out and their biological functions were determined. The ceRNA network containing three hub OMDEGs and five differentially expressed miRNAs (DEmiRNAs) was built. The correlation analysis between hub OMDEGs and OLF-related infiltrating immune cells indicated that metabolic disorder might contribute to the OLF via altering the local immune status of LF tissues. The cell experiments determined the important roles of GBE1 expression and TNF-α in the osteogenic differentiation of LF cells. Conclusions: This research, for the first time, preliminarily illustrated the vital role of metabolic disorder in the pathogenesis of OLF using strict bioinformatic algorithms and experimental validation for metabolism-related genes, which could provide new insights for investigating disease mechanism and screening effective therapeutic targets of OLF in the future.

3.
J Pathol Inform ; 15: 100386, 2024 Dec.
Article de Anglais | MEDLINE | ID: mdl-39006998

RÉSUMÉ

In digital pathology, whole-slide images (WSIs) are widely used for applications such as cancer diagnosis and prognosis prediction. Vision transformer (ViT) models have recently emerged as a promising method for encoding large regions of WSIs while preserving spatial relationships among patches. However, due to the large number of model parameters and limited labeled data, applying transformer models to WSIs remains challenging. In this study, we propose a pretext task to train the transformer model in a self-supervised manner. Our model, MaskHIT, uses the transformer output to reconstruct masked patches, measured by contrastive loss. We pre-trained MaskHIT model using over 7000 WSIs from TCGA and extensively evaluated its performance in multiple experiments, covering survival prediction, cancer subtype classification, and grade prediction tasks. Our experiments demonstrate that the pre-training procedure enables context-aware understanding of WSIs, facilitates the learning of representative histological features based on patch positions and visual patterns, and is essential for the ViT model to achieve optimal results on WSI-level tasks. The pre-trained MaskHIT surpasses various multiple instance learning approaches by 3% and 2% on survival prediction and cancer subtype classification tasks, and also outperforms recent state-of-the-art transformer-based methods. Finally, a comparison between the attention maps generated by the MaskHIT model with pathologist's annotations indicates that the model can accurately identify clinically relevant histological structures on the whole slide for each task.

4.
Br J Dermatol ; 2024 Jul 15.
Article de Anglais | MEDLINE | ID: mdl-39009432

RÉSUMÉ

BACKGROUND: Skin fibrosis is the most typical pathological manifestation of systemic sclerosis (SSc) and localized scleroderma (LS) with unclear etiology and few effective treatments. Though excessive collagen secretion by fibroblasts is the primary cause of skin fibrosis, many lines of evidence suggested that vascular damage was the initiating event and various cell types along with fibroblasts worked together to contribute to the pathogenesis of skin fibrosis. OBJECTIVES: We sought to explore the relationships between vascular endothelial cell lesions and immune cell infiltration, along with the cell-cell interactions among various cell types within the fibrotic skin ecosystem. METHODS: Single-cell RNA-seq (10x Genomics) was performed on skin biopsies of 3 healthy donors and 7 SSc patients in Chinese. The additional 3 localized scleroderma patients' data from NCBI database (GSE160536) were integrated by Harmony. CellChat package (v1.5.0) was applied to analyze cell communication network. Transwell assay and subcutaneous bleomycin (BLM) injection in mice were used to explore the role of ACKR1 on immune cell infiltration. Milo single-cell western blot was applied to show the activation of fibroblast subclusters. RESULTS: A total of 62,295 cells were obtained and subpopulations of stromal and immune cells were identified. Interaction network analysis revealed that multiple chemokines secreted by macrophages, pericytes, and pro-inflammatory fibroblasts could bind with Duffy antigen/receptor for chemokines (ACKR1), which is highly expressed on ACKR1+ endothelial cells of lesion skin. Transwell assay revealed that over-expressed ACKR1 in HUVEC facilitated leukocyte infiltration under the treatment of IL8. The BLM mice showed enhanced ACKR1 expression, massive immune cell infiltration, and fibrosis in skin, which could be attenuated by ACKR1 inhibition. Furthermore, infiltrated macrophages with TGFB1 or PDGFB high production could activate SFRP2/ASPN+ fibroblasts to contribute to excessive accumulation of extracellular matrix (ECM), and the SOX4-ASPN axis plays an important role in the TGF-ß signaling cascade and the etiology of skin fibrosis. CONCLUSIONS: Our results reveal that highly expressed ACKR1 in endothelial cells of fibrotic skin tissue promotes immune cell infiltration, and SFRP2/ASPN+ fibroblasts synergize to exacerbate skin fibrosis.

6.
ISA Trans ; 2024 Jul 03.
Article de Anglais | MEDLINE | ID: mdl-38972822

RÉSUMÉ

This article delves into the intricate challenge of implementing prescribed-time command filtered control in the context of uncertain nonlinear systems. Firstly, a prescribed-time function is defined to lay the groundwork for subsequent controller design. Subsequently, a novel prescribed-time command Filtered controller is proposed for high-order nonlinear systems featuring unknown parameters. This controller guarantees swift error convergence within a predefined time range, with the added capability of periodic error convergence to zero during subsequent controller operations. A pivotal innovation in this study lies in the controller's design, which remains unaffected by the system's initial conditions. This unique feature enables the prescribed time to be flexibly set within physical constraints, diverging markedly from conventional finite-time control theory. Theoretical analysis has conclusively shown that the controller achieves full-state tracking error convergence within the specified time frame. The efficacy of the research findings is substantiated through two simulation cases, underscoring a substantial contribution to the refinement and adaptability of nonlinear system control theory.

7.
Medicine (Baltimore) ; 103(30): e39069, 2024 Jul 26.
Article de Anglais | MEDLINE | ID: mdl-39058823

RÉSUMÉ

Infertility can lead to significant psychological distress among women, yet the roles of hope and resilience in mitigating depressive symptoms remain inadequately explored, particularly within the Chinese context. We performed a cross-sectional observational study to investigate the psychological impacts of infertility among Chinese women as well as to discern whether hope and resilience can influence their depressive symptoms. We recruited 364 Chinese women seeking infertility treatment in the Shandong region. Participants completed validated assessments including the Hospital Anxiety and Depression Scale, Connor-Davidson Resilience Scale, and Herth Hope Index. Demographic and clinical data were also collected. We observed elevated levels of depressive symptoms and anxiety among women with infertility. Particularly, demographic factors such as an older age, rural residence, lower income, lower education, adverse life events, and longer infertility duration were associated with increased depressive symptoms. Individuals who experienced adverse life events were at a 2.42-fold increased risk of developing depressive symptoms (P = .04). Depressive symptoms were inversely correlated with both hope levels (r = -0.25; P < .05) and resilience levels (r = -0.32; P < .05). Hope levels were positively correlated with resilience (R = 0.67; P < .05). After controlling for the interaction of hope and resilience, we found that only depressive symptoms and resilience were negatively correlated. The psychological burden of infertility among Chinese women is widespread and affects many individuals from different demographic backgrounds. Interventions aimed at increasing resilience may be helpful to mitigate depressive symptoms.


Sujet(s)
Adaptation psychologique , Dépression , Résilience psychologique , Humains , Femelle , Études transversales , Adulte , Dépression/psychologie , Dépression/épidémiologie , Chine/épidémiologie , Infertilité féminine/psychologie , Espoir ,
8.
Adv Sci (Weinh) ; : e2400486, 2024 Jul 08.
Article de Anglais | MEDLINE | ID: mdl-38978328

RÉSUMÉ

The risk for suffering immune checkpoint inhibitors (ICIs)-associated myocarditis increases in patients with pre-existing conditions and the mechanisms remain to be clarified. Spatial transcriptomics, single-cell RNA sequencing, and flow cytometry are used to decipher how anti-cytotoxic T lymphocyte antigen-4 m2a antibody (anti-CTLA-4 m2a antibody) aggravated cardiac injury in experimental autoimmune myocarditis (EAM) mice. It is found that anti-CTLA-4 m2a antibody increases cardiac fibroblast-derived C-X-C motif chemokine ligand 1 (Cxcl1), which promots neutrophil infiltration to the myocarditic zones (MZs) of EAM mice via enhanced Cxcl1-Cxcr2 chemotaxis. It is identified that the C-C motif chemokine ligand 5 (Ccl5)-neutrophil subpopulation is responsible for high activity of cytokine production, adaptive immune response, NF-κB signaling, and cellular response to interferon-gamma and that the Ccl5-neutrophil subpopulation and its-associated proinflammatory cytokines/chemokines promoted macrophage (Mφ) polarization to M1 Mφ. These altered infiltrating landscape and phenotypic switch of immune cells, and proinflammatory factors synergistically aggravated anti-CTLA-4 m2a antibody-induced cardiac injury in EAM mice. Neutralizing neutrophils, Cxcl1, and applying Cxcr2 antagonist dramatically alleviates anti-CTLA-4 m2a antibody-induced leukocyte infiltration, cardiac fibrosis, and dysfunction. It is suggested that Ccl5-neutrophil subpopulation plays a critical role in aggravating anti-CTLA-4 m2a antibody-induced cardiac injury in EAM mice. This data may provide a strategic rational for preventing/curing ICIs-associated myocarditis.

9.
Thromb J ; 22(1): 69, 2024 Jul 29.
Article de Anglais | MEDLINE | ID: mdl-39075498

RÉSUMÉ

OBJECTIVE: Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO. METHODS: Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic). RESULTS: The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group. CONCLUSION: The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin.

10.
Nano Lett ; 24(30): 9202-9211, 2024 Jul 31.
Article de Anglais | MEDLINE | ID: mdl-39037031

RÉSUMÉ

The formation of a protein corona gives nanomedicines a distinct biological identity, profoundly influencing their fate in the body. Nonspecific nanoparticle-protein interactions are typically highly heterogeneous, which can lead to unique biological behaviors and in vivo fates for individual nanoparticles that remain underexplored. To address this, we have established an in situ approach that allows quantitative examination of nanoparticle-protein adsorption at the individual nanoparticle level. This method integrates dual fluorescence quantification techniques, wherein the nanoparticles are first individually analyzed via nanoflow cytometry to detect fluorescent signals from adsorbed proteins. The obtained fluorescence intensity is then translated into protein quantities through calibration with microplate reader quantification. Consequently, this approach enables analysis of interparticle heterogeneity of nano-protein interactions, as well as in situ monitoring of protein adsorption kinetics and nanoparticle aggregation status in blood serum, preconditioning for a comprehensive understanding of nano-bio interactions, and predicting in vivo fate of nanomedicines.


Sujet(s)
Protéines du sang , Nanoparticules , Adsorption , Nanoparticules/composition chimique , Protéines du sang/composition chimique , Protéines du sang/analyse , Humains , Couronne de protéines/composition chimique , Fluorescence , Cinétique
11.
Hum Cell ; 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38907140

RÉSUMÉ

The regeneration of peripheral nerves after injury is often slow and impaired, which may be associated with weakened and denervated muscles subsequently leading to atrophy. Adipose-derived stem cells (ADSCs) are often regarded as cell-based therapeutic candidate due to their regenerative potential. The study aims to assess the therapeutic efficacy of gene-modified ADSCs on sciatic nerve injury. We lentivirally transduced ADSCs with shRNA-TWIST1 and transplanted modified cells to rats undergoing sciatic nerve transection and repair. Results showed that TWIST1 knockdown accelerated functional recovery of rats with sciatic nerve injury as faster nerve conduction velocity and higher wire hang scores obtained by rats transplanted with TWIST1-silenced ADSCs than scramble ADSCs. Although the rats experienced degenerated axons and decreased myelin sheath thickness after sciatic nerve injury 8 weeks after operation, those transplanted with TWIST1-silenced ADSCs exhibited more signs of regenerated nerve fibers surrounded by newly formed myelin sheaths than those with scramble ADSCs. The rats transplanted with TWIST1-silenced ADSCs presented increased expressions of neurotrophic factors including neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) in the sciatic nerves than those with scramble ADSCs. These results suggest that genetically modifying TWIST1 in ADSCs could facilitate peripheral nerve repair after injury in a more efficient way than that with ADSCs alone.

12.
J Agric Food Chem ; 72(27): 15237-15247, 2024 Jul 10.
Article de Anglais | MEDLINE | ID: mdl-38935870

RÉSUMÉ

Hemoglobin is an excellent source of iron supplements, and its hydrolyzate spontaneously binds iron during digestion and promotes iron absorption in vivo. However, the underlying mechanisms of what peptides bind and how they bind iron ions remain unclear. This study prepared the porcine hemoglobin hydrolyzate through enzymatic hydrolysis and acid treatment and investigated the mechanisms of hemoglobin hydrolyzate on iron absorption through the determination of iron levels in dietary intervention mice, iron binding site analyses, peptide digestion analyses, molecular simulation docking, and INT407 cell validation. The results showed that ingestion of the hemoglobin hydrolyzate diets increased iron levels in the blood of mice, accompanied by the upregulation of duodenal iron circulation-related genes such as ferritin, PCBP1, and HP. Carboxyl, imidazole groups, and aromatic amino acid residues were iron binding sites of hemoglobin hydrolyzate during digestion. VDEVGGEA and VDEVGGE were found to involve the spontaneous and efficient binding of hemoglobin hydrolyzate to iron ions in the intestinal cavity. In particular, the DEVGGE peptide was the typical sequence for hemoglobin hydrolytic peptides to exert iron binding activity.


Sujet(s)
Hémoglobines , Absorption intestinale , Intestin grêle , Fer , Peptides , Animaux , Hémoglobines/métabolisme , Hémoglobines/composition chimique , Fer/métabolisme , Fer/composition chimique , Souris , Peptides/composition chimique , Peptides/métabolisme , Suidae , Intestin grêle/métabolisme , Humains , Hydrolyse , Mâle , Sites de fixation , Simulation de docking moléculaire , Liaison aux protéines
13.
ACS Nano ; 18(26): 16413-16449, 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38904346

RÉSUMÉ

Layered double hydroxides (LDHs), especially those containing nickel (Ni), are increasingly recognized for their potential in photo(-/)electrocatalytic water oxidation due to the abundant availability of Ni, their corrosion resistance, and their minimal toxicity. This review provides a comprehensive examination of Ni-based LDHs in electrocatalytic (EC), photocatalytic (PC), and photoelectrocatalytic (PEC) water oxidation processes. The review delves into the operational principles, highlighting similarities and distinctions as well as the benefits and limitations associated with each method of water oxidation. It includes a detailed discussion on the synthesis of monolayer, ultrathin, and bulk Ni-based LDHs, focusing on the merits and drawbacks inherent to each synthesis approach. Regarding the EC oxygen evolution reaction (OER), strategies to improve catalytic performance and insights into the structural evolution of Ni-based LDHs during the electrocatalytic process are summarized. Furthermore, the review extensively covers the advancements in Ni-based LDHs for PEC OER, including an analysis of semiconductors paired with Ni-based LDHs to form photoanodes, with a focus on their enhanced activity, stability, and underlying mechanisms facilitated by LDHs. The review concludes by addressing the challenges and prospects in the development of innovative Ni-based LDH catalysts for practical applications. The comprehensive insights provided in this paper will not only stimulate further research but also engage the scientific community, thus driving the field of photo(-/)electrocatalytic water oxidation forward.

14.
Int J Biol Macromol ; 277(Pt 1): 133477, 2024 Jun 26.
Article de Anglais | MEDLINE | ID: mdl-38942413

RÉSUMÉ

The highly efficient removal of oils such as oils or dyes from wastewater has aroused wide concern and is of great significance for clean production and environmental remediation. The synthesis of a novel aerogel (designated as HEC/LS) is reported herein, achieved through a sol-gel method followed by freeze-drying utilizing loofa and hydroxyethyl cellulose as the raw materials. The new HEC/LS aerogel exhibits excellent porosity and specific surface area, with a porosity of 88.70 %, a total pore area of 0.607 m2 g-1, and a specific surface area of 230 m2 g-1. The prepared HEC/LS aerogel exhibits exceptional hydrophilicity and self-floatability, facilitating its rapid absorption of water up to 21 times its own weight within a mere 3 s. Additionally, it demonstrates good adsorption performance for methylene blue (MB), with a maximum adsorption capacity of 83.30 mg g-1. Subsequently, a new hydrophobic microorganisms-loaded composite aerogel (namely, Bn-HEC/LS) was obtained by doping microorganisms into the as-prepared HEC/LS in multiple enrichment followed by a hydrophobic and oleophilic surface modification. Based on its rich porous structure and oleophilic wettability, the as-synthesized Bn-HEC/LS exhibits excellent selective adsorption and degradation properties for the oil contamination, the diesel oil could be selectively absorbed in the Bn-HEC/LS and degraded by the loaded microorganisms. Among them, B5-HEC/LS displays the highest removal efficiency of 94.50 % within 180 h, while free microorganisms and HEC/LS aerogels show degradation efficiencies of only 21.70 % and 48.10 %, respectively. The fixation of microorganisms in the aerogel increases their number within the material and enhances the relative microorganisms removal capacity. The hydrophobic and lipophilic modifications improve the selective adsorption performance of the aerogel on diesel oil, resulting in a significantly high removal rate of Bn-HEC/LS for diesel oil. The results indicate that the immobilization of microorganisms into aerogel improves the activity of microorganisms, and the hydrophobic and oleophilic modification enhances the selective adsorption performance of aerogel to diesel oil, thus resulting in a very high removal rate of Bn-HEC/LS for diesel oil. This study is expected to provide a now possibility for the green and efficient bioremediation of oils.

15.
Chin Med J (Engl) ; 137(14): 1651-1662, 2024 Jul 20.
Article de Anglais | MEDLINE | ID: mdl-38867424

RÉSUMÉ

ABSTRACT: Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.


Sujet(s)
Arthrite , Fer , Humains , Fer/métabolisme , Arthrite/métabolisme , Arthrite/traitement médicamenteux , Homéostasie , Animaux
16.
Chem Biodivers ; : e202400954, 2024 Jun 06.
Article de Anglais | MEDLINE | ID: mdl-38844419

RÉSUMÉ

Lycopodiales, an order comprising 388 distinct species, is the source of Lycopodium alkaloids (LAs), a group of naturally occurring alkaloids that share a common biosynthesis and structural attributes. These remarkable organisms are considered vestiges of ancient ferns, with fossil evidence dating their existence back to an impressive 300 million years. LAs usually are tricyclic or tetracyclic compounds with C16N or C16N2 skeleton. But then there are also have a few C11N, C15N, C15N2, C22N2, and C27N3 skeleton. LAs have attracted much scientific attention because of their important biological activities related to acetylcholinesterase and unique structural characteristics. From 1881 to December 2023, there are 593 LAs from 49 species of Lycopodiales have been reported. Because the total amount of LAs is nearly five times that of 1994, the classification and group allocation of some newly isolated LAs is often challenging and not unambiguous by Ayer's simple classification. This review makes a more systematic and detailed classification for it and provides extensive coverage of naturally occurring LAs discovered from 1881 to December 2023. Until now, there is no comprehensively summary of biological activity of the LAs. This review is the first time covered the biological activity of the all LAs.

17.
J Cardiovasc Pharmacol ; 84(1): 71-80, 2024 Jul 01.
Article de Anglais | MEDLINE | ID: mdl-38922574

RÉSUMÉ

ABSTRACT: Clinical practice shows that a critical unmet need in the field of thrombosis prevention is the availability of anticoagulant therapy without bleeding risk. Inhibitors against FXIa or FXIIa have been extensively studied because of their low bleeding risk. However, whether these compounds produce synergistic effects has not yet been explored. In this study, analyses of activated partial thromboplastin time in combination with the FXIa inhibitor PN2KPI and the FXIIa inhibitor Infestin4 at different proportions were performed using the SynergyFinder tool identifying synergistic anticoagulation effects. Both an FeCl 3 -induced carotid artery thrombosis mouse model and a transient occlusion of the middle cerebral artery mouse model showed that the combination of PN2KPI and Infestin4, which are 28.57% and 6.25% of the effective dose, respectively, significantly prevents coagulation, and furthermore, dual inhibition does not cause bleeding risk.


Sujet(s)
Anticoagulants , Coagulation sanguine , Modèles animaux de maladie humaine , Synergie des médicaments , Facteur XIIa , Facteur XIa , Animaux , Facteur XIa/antagonistes et inhibiteurs , Facteur XIa/métabolisme , Anticoagulants/pharmacologie , Coagulation sanguine/effets des médicaments et des substances chimiques , Mâle , Facteur XIIa/antagonistes et inhibiteurs , Facteur XIIa/métabolisme , Thrombose carotidienne/prévention et contrôle , Thrombose carotidienne/induit chimiquement , Thrombose carotidienne/traitement médicamenteux , Souris , Infarctus du territoire de l'artère cérébrale moyenne/traitement médicamenteux , Hémorragie/induit chimiquement , Souris de lignée C57BL , Temps partiel de thromboplastine
18.
JAMA Netw Open ; 7(5): e2413213, 2024 May 01.
Article de Anglais | MEDLINE | ID: mdl-38805227

RÉSUMÉ

Importance: The ratio of red blood cell distribution width (RDW) to albumin concentration (RAR) has emerged as a reliable prognostic marker for mortality in patients with various diseases. However, whether RAR is associated with mortality in the general population remains unknown. Objectives: To explore whether RAR is associated with all-cause and cause-specific mortality and to elucidate their dose-response association. Design, Setting, and Participants: This population-based prospective cohort study used data from participants in the 1998-2018 US National Health and Nutrition Examination Survey (NHANES) and from the UK Biobank with baseline information provided from 2006 to 2010. Included participants had complete data on serum albumin concentration, RDW, and cause of death. The NHANES data were linked to the National Death Index records through December 31, 2019. For the UK Biobank, dates and causes of death were obtained from the National Health Service Information Centre (England and Wales) and the National Health Service Central Register Scotland (Scotland) to November 30, 2022. Main Outcomes and Measures: Potential associations between RAR and the risk of all-cause and cause-specific mortality were evaluated using Cox proportional hazards regression models. Restricted cubic spline regressions were applied to estimate possible nonlinear associations. Results: In NHANES, 50 622 participants 18 years of age or older years were included (mean [SD] age, 48.6 [18.7] years; 26 136 [51.6%] female), and their mean (SD) RAR was 3.15 (0.51). In the UK Biobank, 418 950 participants 37 years of age or older (mean [SD], 56.6 [8.1] years; 225 038 [53.7%] female) were included, and their mean RAR (SD) was 2.99 (0.31). The NHANES documented 7590 deaths over a median (IQR) follow-up of 9.4 (5.1-14.2) years, and the UK Biobank documented 36 793 deaths over a median (IQR) follow-up of 13.8 (13.0-14.5) years. According to the multivariate analysis, elevated RAR was significantly associated with greater risk of all-cause mortality (NHANES: hazard ratio [HR], 1.83 [95% CI, 1.76-1.90]; UK Biobank: HR, 2.08 [95% CI, 2.03-2.13]), as well as mortality due to malignant neoplasm (NHANES: HR, 1.89 [95% CI, 1.73-2.07]; UK Biobank: HR, 1.93 [95% CI, 1.86-2.00]), heart disease (NHANES: HR, 1.88 [95% CI, 1.74-2.03]; UK Biobank: HR, 2.42 [95% CI, 2.29-2.57]), cerebrovascular disease (NHANES: HR, 1.35 [95% CI, 1.07-1.69]; UK Biobank: HR, 2.15 [95% CI, 1.91-2.42]), respiratory disease (NHANES: HR, 1.99 [95% CI, 1.68-2.35]; UK Biobank: HR, 2.96 [95% CI, 2.78-3.15]), diabetes (NHANES: HR, 1.55 [95% CI, 1.27-1.90]; UK Biobank: HR, 2.83 [95% CI, 2.35-3.40]), and other causes of mortality (NHANES: HR, 1.97 [95% CI, 1.86-2.08]; UK Biobank: HR, 2.40 [95% CI, 2.30-2.50]) in both cohorts. Additionally, a nonlinear association was observed between RAR levels and all-cause mortality in both cohorts. Conclusions and Relevance: In this cohort study, a higher baseline RAR was associated with an increased risk of all-cause and cause-specific mortality in the general population. These findings suggest that RAR may be a simple, reliable, and inexpensive indicator for identifying individuals at high risk of mortality in clinical practice.


Sujet(s)
Index érythrocytaires , Enquêtes nutritionnelles , Humains , Femelle , Mâle , Adulte d'âge moyen , Études prospectives , Adulte , Sujet âgé , Cause de décès , États-Unis/épidémiologie , Sérumalbumine/analyse , Modèles des risques proportionnels , Mortalité , Facteurs de risque , Marqueurs biologiques/sang , Royaume-Uni/épidémiologie
19.
BMC Musculoskelet Disord ; 25(1): 418, 2024 May 28.
Article de Anglais | MEDLINE | ID: mdl-38807200

RÉSUMÉ

BACKGROUND: It was reported the paraspinal muscle played an important role in spinal stability. The preoperative paraspinal muscle was related to S1 screw loosening. But the relationship between preoperative and postoperative change of psoas major muscle (PS) and S1 pedicle screw loosening in degenerative lumbar spinal stenosis (DLSS) patients has not been reported. This study investigated the effects of preoperative and follow-up variations in the psoas major muscle (PS) on the first sacral vertebra (S1) screw loosening in patients with DLSS. METHODS: 212 patients with DLSS who underwent lumbar surgery were included. The patients were divided into the S1 screw loosening group and the S1 screw non-loosening group. Muscle parameters were measured preoperatively and at last follow-up magnetic resonance imaging. A logistic regression analysis was performed to investigate the risk factors for S1 screw loosening. RESULTS: The S1 screw loosening rate was 36.32% (77/212). The relative total cross-sectional areas and relative functional cross-sectional areas (rfCSAs) of the PS at L2-S1 were significantly higher after surgery. The increased rfCSA values of the PS at L3-S1 in the S1 screw non-loosening group were significantly higher than those in the S1 screw loosening group. The regression analysis showed male, lower CT value of L1 and longer segment fusion were independent risk factors for S1 screw loosening, and postoperative hypertrophy of the PS was a protective factor for S1 screw loosening. CONCLUSIONS: Compared to the preoperative muscle, the PS size increased and fatty infiltration decreased after surgery from L2-3 to L5-S1 in patients with DLSS after short-segment lumbar fusion surgery. Postoperative hypertrophy of the PS might be considered as a protective factor for S1 screw loosening. MRI morphometric parameters and postoperative selected exercise of PS for DLSS patients after posterior lumbar fusion surgery might contribute to improvement of surgical outcome.


Sujet(s)
Vertèbres lombales , Vis pédiculaires , Muscle iliopsoas , Arthrodèse vertébrale , Sténose du canal vertébral , Humains , Mâle , Sténose du canal vertébral/chirurgie , Sténose du canal vertébral/imagerie diagnostique , Femelle , Vertèbres lombales/chirurgie , Vertèbres lombales/imagerie diagnostique , Sujet âgé , Muscle iliopsoas/imagerie diagnostique , Adulte d'âge moyen , Études de suivi , Arthrodèse vertébrale/instrumentation , Arthrodèse vertébrale/effets indésirables , Imagerie par résonance magnétique , Sacrum/imagerie diagnostique , Sacrum/chirurgie , Études rétrospectives , Facteurs de risque , Sujet âgé de 80 ans ou plus , Période préopératoire
20.
Front Pediatr ; 12: 1390856, 2024.
Article de Anglais | MEDLINE | ID: mdl-38803636

RÉSUMÉ

Background: Intestinal malrotation is a rare condition, and its delayed diagnosis can lead to fatal consequences. This study aimed to investigate the identification and treatment of malrotation in children. Methods: Clinical data, imaging, operative findings, and early postoperative outcomes of 75 children with malrotation were retrospectively analyzed. Results: The mean age was 6.18 ± 4.93 days and 51.26 ± 70.13 months in the neonatal group (56 patients) and non-neonatal group (19 patients), respectively. Sixty-seven patients were under the age of 1 year at the time of diagnosis. The occurrence of bilious vomiting and jaundice was significantly higher in the neonatal group (89.29%) than that in the non-neonatal group (37.5%), p < 0.05 and p < 0.01, respectively. The incidence of abnormal ultrasound (US) findings was 97.30% and 100%, respectively, and the sensitivities of the upper gastrointestinal series were 84.21% and 87.5%, respectively. Sixty-six (88%) patients had midgut volvulus, including in utero volvulus (two patients) and irreversible intestinal ischemia (four patients). Most neonates (89.29%) underwent open Ladd's procedure with a shorter operative time (p < 0.01). Reoperation was performed for postoperative complications (four patients) or missed comorbidities (two patients). Conclusions: Non-bilious vomiting was the initial symptom in >10% of neonates and nearly 40% of non-neonates. This highlights the importance for emergency physicians and surgeons to be cautious about ruling out malrotation in patients with non-bilious vomiting. Utilizing US can obviate the need for contrast examinations owing to its higher diagnostic accuracy and rapid diagnosis and can be recommended as a first-line imaging technique. Additionally, open surgery is still an option for neonatal patients.

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