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1.
Sci Prog ; 107(2): 368504241253709, 2024.
Article in English | MEDLINE | ID: mdl-38778725

ABSTRACT

Inflammatory bowel disease (IBD) is a chronic inflammatory disease with increasing incidence, such as Crohn's disease and ulcerative colitis. The accurate etiology and pathogenesis of IBD remain unclear, and it is generally believed that it is related to genetic susceptibility, gut microbiota, environmental factors, immunological abnormalities, and potentially other factors. Currently, the mainstream therapeutic drugs are amino salicylic acid agents, corticosteroids, immunomodulators, and biological agents, but the remission rates do not surpass 30-60% of patients in a real-life setting. As a consequence, there are many studies focusing on emerging drugs and bioactive ingredients that have higher efficacy and long-term safety for achieving complete deep healing. This article begins with a review of the latest, systematic, and credible summaries of the pathogenesis of IBD. In addition, we provide a summary of the current treatments and drugs for IBD. Finally, we focus on the therapeutic effects of emerging drugs such as microRNAs and lncRNAs, nanoparticles-mediated drugs and natural products on IBD and their mechanisms of action.


Subject(s)
Inflammatory Bowel Diseases , Humans , Inflammatory Bowel Diseases/drug therapy , MicroRNAs/genetics , Biological Products/therapeutic use , Gastrointestinal Microbiome/drug effects , Animals , RNA, Long Noncoding/genetics
2.
J Agric Food Chem ; 72(21): 12072-12082, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38750669

ABSTRACT

Ganoderma lucidum polysaccharide (GLP) is a prebiotic with immunomodulatory effects. However, the therapeutic potential of GLP in tumor immunotherapy has not been fully explored, especially in T cell-mediated antitumor immunity. In this study, we found that GLP significantly inhibited tumor growth and activated antitumor immunity in colorectal cancer (CRC). In the spleens and tumor tissues, the proportion of cytotoxic CD8+T cells and Th1 helper cells increased, while immunosuppressive Tregs decreased. Additionally, microbiota dysbiosis was alleviated by GLP, and short-chain fatty acid production was increased. Meanwhile, GLP decreased the ratio of kynurenine and tryptophan (Kyn/Trp) in the serum, which contributed to antitumor immunity of T cells. More importantly, the combination of GLP and the immune checkpoint inhibitor anti-PD-1 monoclonal antibody further enhanced the efficacy of anti-PD-1 immunotherapy. Thus, GLP as a prebiotic has the potential to be used in tumor immunotherapy.


Subject(s)
Colorectal Neoplasms , Immunotherapy , Polysaccharides , Programmed Cell Death 1 Receptor , Reishi , Colorectal Neoplasms/immunology , Colorectal Neoplasms/drug therapy , Animals , Reishi/chemistry , Mice , Humans , Programmed Cell Death 1 Receptor/immunology , Polysaccharides/pharmacology , Mice, Inbred BALB C , Cell Line, Tumor , Male , Female , T-Lymphocytes/immunology , T-Lymphocytes/drug effects , Immune Checkpoint Inhibitors/pharmacology , Immunity, Cellular/drug effects
3.
Photodiagnosis Photodyn Ther ; 47: 104218, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38777310

ABSTRACT

PURPOSE: To facilitate the assessment of choroid vascular layer thickness in patients with wet age-related macular degeneration (AMD) using artificial intelligence (AI). METHODS: We included 194 patients with wet AMD and 225 healthy participants. Choroid images were obtained using swept-source optical coherence tomography. The average Sattler layer-choriocapillaris complex thickness (SLCCT), Haller layer thickness (HLT), and choroidal thickness (CT) were auto-measured at 7 regions centered around the foveola using AI and subsequently compared between the 2 groups. RESULTS: The SLCCT was lower in the AMD group than in the control group (P < 0.05). The HLT was significantly higher in the AMD group than in the control group at the Tparafovea and T-perifovea in the total population (P < 0.05) and in the ≤70-year subgroup (P < 0.05). The CT was higher in the AMD group than in the control group, particularly at the N-perifovea, T-perifovea, and T-parafovea in the ≤70-year subgroup; Interestingly, it was lower in the AMD group than in the control group at the Nparafovea, N-fovea, foveola, and T-fovea in the >70-year subgroup (P < 0.05). CONCLUSION: This novel AI-based auto-measurement was more accurate, efficient, and detailed than manual measurements. SLCCT thinning was observed in wet AMD; however, CT changes depended on the interaction between HLT compensatory thickening and SLCCT thinning.

4.
Sci Rep ; 14(1): 9510, 2024 04 25.
Article in English | MEDLINE | ID: mdl-38664443

ABSTRACT

Clinical ulcerative colitis (UC) is a heterogeneous condition. Moreover, medical interventions are nonspecific, and thus, treatment responses are inconsistent. The aim of this study was to explore the molecular subtypes and biological characteristics of UC based on ferroptosis and neutrophil gene sets. Multiple intestinal mucosa gene expression profiles of UC patients in the Gene Expression Omnibus (GEO) database were downloaded. Unsupervised clustering methods were used to identify potential molecular subtypes based on ferroptosis and neutrophil gene sets. Multiple immune infiltration algorithms were used to evaluate the biological characteristics of the molecular subtypes. Machine learning identifies hub genes for molecular subtypes and analyses their diagnostic efficacy for UC and predictive performance for drug therapy. The relevant conclusions were verified by clinical samples and animal experiments. Four molecular subtypes were identified according to the ferroptosis and neutrophil gene sets: neutrophil, ferroptosis, mixed and quiescent. The subtypes have different biological characteristics and immune infiltration levels. Multiple machine learning methods jointly identified four hub genes (FTH1, AQP9, STEAP3 and STEAP4). Receiver operating characteristic (ROC) curve analysis revealed that the four hub genes could be used as diagnostic markers for UC. The clinical response profile data of infliximab treatment patients showed that AQP9 and STEPA4 were reliable predictors of infliximab treatment response. In human samples the AQP9 and STEAP4 protein were shown to be increased in UC intestinal samples. In animal experiments, the ferroptosis and neutrophil phenotype were confirmed. Dual analysis of ferroptosis and neutrophil gene expression revealed four subgroups of UC patients. The molecular subtype-associated hub genes can be used as diagnostic markers for UC and predict infliximab treatment response.


Subject(s)
Colitis, Ulcerative , Ferroptosis , Neutrophil Infiltration , Ferroptosis/genetics , Colitis, Ulcerative/genetics , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Humans , Animals , Neutrophil Infiltration/genetics , Neutrophils/metabolism , Neutrophils/immunology , Infliximab/therapeutic use , Infliximab/pharmacology , Machine Learning , Mice , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Gene Expression Profiling/methods , Male , Female
6.
ACS Nano ; 18(17): 11042-11057, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38627898

ABSTRACT

PD-1 blockade is a first-line treatment for recurrent/metastatic cervical cancer but benefits only a small number of patients due to low preexisting tumor immunogenicity. Using immunogenic cell death (ICD) inducers is a promising strategy for improving immunotherapy, but these compounds are limited by the hypoxic environment of solid tumors. To overcome this issue, the nanosensitizer AIBA@MSNs were designed based on sonodynamic therapy (SDT), which induces tumor cell death under hypoxic conditions through azo free radicals in a method of nonoxygen radicals. Mechanistically, the azo free radicals disrupt both the structure and function of tumor mitochondria by reversing the mitochondrial membrane potential and facilitating the collapse of electron transport chain complexes. More importantly, the AIBA@MSN-based SDT serves as an effective ICD inducer and improves the antitumor immune capacity. The combination of an AIBA@MSN-based SDT with a PD-1 blockade has the potential to improve response rates and provide protection against relapse. This study provides insights into the use of azo free radicals as a promising SDT strategy for cancer treatment and establishes a basic foundation for nonoxygen-dependent SDT-triggered immunotherapy in cervical cancer treatment.


Subject(s)
Immunotherapy , Uterine Cervical Neoplasms , Uterine Cervical Neoplasms/therapy , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/immunology , Female , Free Radicals/chemistry , Humans , Mice , Animals , Azo Compounds/chemistry , Azo Compounds/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Mice, Inbred BALB C , Drug Screening Assays, Antitumor , Cell Proliferation/drug effects , Membrane Potential, Mitochondrial/drug effects
7.
J Affect Disord ; 354: 1-10, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38452936

ABSTRACT

BACKGROUND: Prenatal depression, associated with adverse effects on mothers and fetuses, has received little attention. We conducted a large-sample study to investigate the risk factors of, and develop a predictive model for, prenatal depression in the Chinese population. METHODS: This study enrolled 14,329 pregnant women who delivered at the West China Second University Hospital, Sichuan University from January 2017 to December 2020. Participants were divided into a training or validation cohort. Multiple variables were collected and selected using univariate logistic regression and least absolute shrinkage and selection operator penalty regression. After multivariate logistic analysis, a predictive model was developed and validated internally and externally. RESULTS: Nine variables (employment, planned pregnancy, pregnancy number, conception methods, gestational diabetes mellitus, twin pregnancy, placenta previa, umbilical cord encirclement, and educational attainment) were identified as independent risk factors for prenatal depression. Receiver operating characteristic curves in both the training and validation cohorts showed excellent discrimination of the predictive model (the area under the curve: 0.746 and 0.732, respectively). LIMITATIONS: The results of this retrospective study may be affected by confounding and information bias. Some important variables were excluded, such as family history of mental disorders. The study was conducted in China; its results may not be generalizable to other regions. CONCLUSION: Our study identified nine significant risk factors for prenatal depression and constructed an accurate predictive model. This model could be applied as a clinical decision aid for individualized risk estimates and prevention of prenatal depression.


Subject(s)
Depression , Diabetes, Gestational , Pregnancy , Humans , Female , Retrospective Studies , Depression/epidemiology , Risk Factors , Logistic Models , Vitamins , China/epidemiology
8.
Carbohydr Polym ; 334: 122035, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38553204

ABSTRACT

Inspired from human skin, micro- and nano-wrinkled wood surface with skin-tactile performance was designed and developed using a waterborne UV-curable polyurethane acrylate coating and cellulose nofibers (CNF). To further improve the properties, the CNF was diacetylated to D-CNF and further grafted with a hyperbranched polymer containing rich end amino groups (HB-CNF). The surface structure and chemical reactions were characterized, and the skin-tactile performance of the coating was comprehensively investigated. The HB-CNF exhibited excellent dispersion in the coating, and extensive reactions occurred between the two through the -NH2 and terminal -NCO groups, resulting in much improved mechanical properties and durability. Micro-wrinkles with a width of approximately 12-15 µm and a height of 8-14 µm were created, and nano-protrusions of wrinkles ranging from to 50-100 nm were obtained. The coated surface was hydrophobic and exhibited high resilience after compression, with a gloss of 3.3 GU at an incident angle of 60° and a static friction coefficient of 0.26, both of which were similar to those of human skin. The results presented an effective strategy for high-performance wood products with a good feeling, which is helpful to improve the market competitiveness and meet the people's pursuit of a better life.

9.
Front Psychiatry ; 15: 1277415, 2024.
Article in English | MEDLINE | ID: mdl-38525255

ABSTRACT

Background: Postpartum depression (PPD) is one of the most common complications of delivery and is usually disregarded. Several risk factors of PPD have been identified, but its pathogenesis has not been completely understood. Serum bilirubin has been found to be a predictor of depression, whose relationship with PPD has not been investigated. Methods: Observational research was performed followed by a two-sample Mendelian randomization (MR) analysis. From 2017 to 2020, the clinical data of pregnant women were retrospectively extracted. Logistic regression and random forest algorithm were employed to assess the risk factors of PPD, including the serum levels of total bilirubin and direct bilirubin. To further explore their potential causality, univariable and multivariable Mendelian randomization (MVMR) were conducted. Sensitivity analyses for MR were performed to test the robustness of causal inference. Results: A total of 1,810 patients were included in the PPD cohort, of which 631 (34.87%) were diagnosed with PPD. Compared with the control group, PPD patients had a significantly lower level of total bilirubin (9.2 µmol/L, IQR 7.7, 11.0 in PPD; 9.7 µmol/L, IQR 8.0, 12.0 in control, P < 0.001) and direct bilirubin (2.0 µmol/L, IQR 1.6, 2.6 in PPD; 2.2 µmol/L, IQR 1.7, 2.9 in control, P < 0.003). The prediction model identified eight independent predictive factors of PPD, in which elevated total bilirubin served as a protective factor (OR = 0.94, 95% CI 0.90-0.99, P = 0.024). In the MR analyses, genetically predicted total bilirubin was associated with decreased risk of PPD (IVW: OR = 0.86, 95% CI 0.76-0.97, P = 0.006), which remained consistent after adjusting educational attainment, income, and gestational diabetes mellitus. Conversely, there is a lack of solid evidence to support the causal relationship between PPD and bilirubin. Conclusion: Our results suggested that decreased total bilirubin was associated with the incidence of PPD. Future studies are warranted to investigate its potential mechanisms and illuminate the pathogenesis of PPD.

10.
Clin Transl Oncol ; 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38512449

ABSTRACT

PURPOSE: Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract, and its unique location within the small intestine presents difficulties in obtaining tissue samples from the lesions. This limitation hinders the research and development of effective clinical treatment methods. Circulating tumor DNA (ctDNA) analysis holds promise as an alternative approach for investigating SBA and guiding treatment decisions, thereby improving the prognosis of SBA. METHODS: Between January 2017 and August 2021, a total of 336 tissue or plasma samples were obtained and the corresponding mutation status in tissue or blood was evaluated with NGS. RESULTS AND CONCLUSIONS: The study found that in SBA tissues, the most commonly alternated genes were TP53, KRAS, and APC, and the most frequently affected pathways were RTK-RAS-MAPK, TP53, and WNT. Notably, the RTK-RAS-MAPK pathway was identified as a potential biomarker that could be targeted for treatment. Then, we validated the gene mutation profiling of ctDNA extracted from SBA patients exhibited the same characteristics as tissue samples for the first time. Subsequently, we applied ctDNA analysis on a terminal-stage patient who had shown no response to previous chemotherapy. After detecting alterations in the RTK-RAS-MAPK pathway in the ctDNA, the patient was treated with MEK + EGFR inhibitors and achieved a tumor shrinkage rate of 76.33%. Our study utilized the largest Chinese SBA cohort to uncover the molecular characteristics of this disease, which might facilitate clinical decision making for SBA patients.

11.
Ophthalmic Res ; 67(1): 211-220, 2024.
Article in English | MEDLINE | ID: mdl-38484716

ABSTRACT

INTRODUCTION: This study aimed to compare retinal vascular parameters and density in patients with moyamoya disease using the optical coherence tomography angiography. METHODS: This clinical trial totally enrolls 78 eyes from 39 participants, and all these patients with moyamoya disease (N = 13) are set as experimental group and participants with health who matched with age and gender are considered as the control group (N = 26). Then all these participants receive optical coherence tomography angiography detection. Participants' general data are collected and analyzed. Skeleton density (SD) value, vessel density (VD) value, fractal dimension (FD) value, vessel diameter index (VDI) value, foveal avascular zone (FAZ) value are analyzed. RESULTS: A total of 39 participants are included in this study. The SD value in the experimental group was significantly lower than that in control group (0.175 [0.166, 0.181] vs. 0.184 [0.175, 0.188], p = 0.017). Similarly, the VD value in the experimental group was significantly lower than that in the control group (0.333 [0.320, 0.350] vs. 0.354 [0.337, 0.364], p = 0.024). Additionally, the FD value in the experimental group was significantly lower than that in the control group (2.088 [2.083, 2.094] vs. 2.096 [2.090, 2.101], p = 0.022). As for the VDI and FAZ, VDI and FAZ values in the experimental group were lower than those in the control group, there was no significant difference in VDI and FAZ values between the two groups. CONCLUSIONS: Our study, using non-invasive and rapid OCTA imaging, confirmed decreased retinal vascular parameters and density in patients with moyamoya disease.


Subject(s)
Fluorescein Angiography , Fundus Oculi , Moyamoya Disease , Retinal Vessels , Tomography, Optical Coherence , Humans , Moyamoya Disease/diagnosis , Moyamoya Disease/physiopathology , Moyamoya Disease/diagnostic imaging , Female , Male , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Tomography, Optical Coherence/methods , Retrospective Studies , Fluorescein Angiography/methods , Adult , Middle Aged , Visual Acuity , Young Adult , Adolescent , Follow-Up Studies
12.
BMC Cancer ; 24(1): 244, 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38389061

ABSTRACT

BACKGROUND: Identifying risk factors for adverse pathologic features in low-risk papillary thyroid microcarcinoma (PTMC) can provide valuable insights into the necessity of surgical or non-surgical treatment. This study aims to develop a nomogram for predicting the probability of adverse pathologic features in low-risk PTMC patients. METHODS: A total of 662 patients with low-risk PTMC who underwent thyroid surgery were retrospectively analyzed in Qilu Hospital of Shandong University from May 2019 to December 2021. Logistic regression analysis was used to determine the risk factors for adverse pathologic features, and a nomogram was constructed based on these factors. RESULTS: Most PTMC patients with these adverse pathologic features had tumor diameters greater than 0.6 cm (p < 0.05). Other factors (age, gender, family history of thyroid cancer, history of autoimmune thyroiditis, and BRAFV600E mutation) had no significant correlation with adverse pathologic features (p > 0.05 each). The nomogram was drawn to provide a quantitative and convenient tool for predicting the risk of adverse pathologic features based on age, gender, family history of thyroid cancer, autoimmune thyroiditis, tumor size, and BRAFV600E mutation in low-risk PTMC patients. The areas under curves (AUC) were 0.645 (95% CI 0.580-0.702). Additionally, decision curve analysis (DCA) and calibration curves were used to evaluate the clinical benefits of this nomogram, presenting a high net benefit. CONCLUSION: Tumor size > 0.60 cm was identified as an independent risk factor for adverse pathologic features in low-risk PTMC patients. The nomogram had a high predictive value and consistency based on these factors.


Subject(s)
Carcinoma, Papillary , Thyroid Neoplasms , Thyroiditis, Autoimmune , Humans , Nomograms , Proto-Oncogene Proteins B-raf/genetics , Retrospective Studies , Thyroid Neoplasms/pathology , Risk Factors
13.
Cereb Cortex ; 34(2)2024 01 31.
Article in English | MEDLINE | ID: mdl-38342685

ABSTRACT

Perinatal depression, with a prevalence of 10 to 20% in United States, is usually missed as multiple symptoms of perinatal depression are common in pregnant women. Worse, the diagnosis of perinatal depression still largely relies on questionnaires, leaving the objective biomarker being unveiled yet. This study suggested a safe and non-invasive technique to diagnose perinatal depression and further explore its underlying mechanism. Considering the non-invasiveness and clinical convenience of electroencephalogram for mothers-to-be and fetuses, we collected the resting-state electroencephalogram of pregnant women at the 38th week of gestation. Subsequently, the difference in network topology between perinatal depression patients and healthy mothers-to-be was explored, with related spatial patterns being adopted to achieve the classification of pregnant women with perinatal depression from those healthy ones. We found that the perinatal depression patients had decreased brain network connectivity, which indexed impaired efficiency of information processing. By adopting the spatial patterns, the perinatal depression could be accurately recognized with an accuracy of 87.88%; meanwhile, the depression severity at the individual level was effectively predicted, as well. These findings consistently illustrated that the resting-state electroencephalogram network could be a reliable tool for investigating the depression state across pregnant women, and will further facilitate the clinical diagnosis of perinatal depression.


Subject(s)
Depression , Depressive Disorder , Female , Pregnancy , Humans , Depression/diagnosis , Scalp , Pregnant Women , Electroencephalography
15.
Quant Imaging Med Surg ; 14(1): 932-943, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38223087

ABSTRACT

Background: As the retinal microvasculature shares similarities with the cerebral microvasculature, numerous studies have shown that retinal vascular is associated with cognitive decline. In addition, several population-based studies have confirmed the association between retinal vascular and cerebral small vessel disease (CSVD) burden. However, the association of retinal vascular with CSVD burden as well as cognitive function has not been explored simultaneously. This study investigated the relations of retinal microvascular parameters (RMPs) with CSVD burden and cognitive function. Methods: We conducted a cross-sectional study of participants in the KaiLuan study. Data were collected from subjects aged ≥18 years old who could complete retinal photography and brain magnetic resonance imaging (MRI) between December 2020 to October 2021 in the Kailuan community of Tangshan. RMPs were evaluated using a deep learning system. The cognitive function was measured using the Montreal Cognitive Assessment (MoCA). We conducted logistic regression models, and mediation analysis to evaluate the associations of RMPs with CSVD burden and cognitive decline. Results: Of the 905 subjects (mean age: 55.42±12.02 years, 54.5% female), 488 (53.9%) were classified with cognitive decline. The fractal dimension (FD) [odds ratio (OR), 0.098, 95% confidence interval (CI): 0.015-0.639, P=0.015] and global vein width (OR: 1.010, 95% CI: 1.005-1.015, P<0.001) were independent risk factors for cognitive decline after adjustment for potential confounding factors. The global artery width was significantly associated with severe CSVD burden (OR: 0.985, 95% CI: 0.974-0.997, P=0.013). The global vein width was sightly associated with severe CSVD burden (OR: 1.005, 95% CI: 1.000-1.010, P=0.050) after adjusting for potential confounders. The multivariable-adjusted odds ratios (95% CI) in highest tertile versus lowest tertile of global vein width were 1.290 (0.901-1.847) for cognitive decline and 1.546 (1.004-2.290) for severe CSVD burden, respectively. Moreover, CSVD burden played a partial mediating role in the association between global vein width and cognitive function (mediating effect 6.59%). Conclusions: RMPs are associated with cognitive decline and the development of CSVD. A proportion of the association between global vein width and cognitive decline may be attributed to the presence of CSVD burden.

16.
BMC Geriatr ; 24(1): 28, 2024 01 06.
Article in English | MEDLINE | ID: mdl-38184539

ABSTRACT

BACKGROUND: The current literature shows a strong relationship between retinal neuronal and vascular alterations in dementia. The purpose of the study was to use NFN+ deep learning models to analyze retinal vessel characteristics for cognitive impairment (CI) recognition. METHODS: We included 908 participants from a community-based cohort followed for over 15 years (the prospective KaiLuan Study) who underwent brain magnetic resonance imaging (MRI) and fundus photography between 2021 and 2022. The cohort consisted of both cognitively healthy individuals (N = 417) and those with cognitive impairment (N = 491). We employed the NFN+ deep learning framework for retinal vessel segmentation and measurement. Associations between Retinal microvascular parameters (RMPs: central retinal arteriolar / venular equivalents, arteriole to venular ratio, fractal dimension) and CI were assessed by Pearson correlation. P < 0.05 was considered statistically significant. The correlation between the CI and RMPs were explored, then the correlation coefficients between CI and RMPs were analyzed. Random Forest nonlinear classification model was used to predict whether one having cognitive decline or not. The assessment criterion was the AUC value derived from the working characteristic curve. RESULTS: The fractal dimension (FD) and global vein width were significantly correlated with the CI (P < 0.05). Age (0.193), BMI (0.154), global vein width (0.106), retinal vessel FD (0.099), and CRAE (0.098) were the variables in this model that were ranked in order of feature importance. The AUC values of the model were 0.799. CONCLUSIONS: Establishment of a predictive model based on the extraction of vascular features from fundus images has a high recognizability and predictive power for cognitive function and can be used as a screening method for CI.


Subject(s)
Cognitive Dysfunction , Deep Learning , Humans , Prospective Studies , Cognitive Dysfunction/diagnostic imaging , Retina , Retinal Vessels/diagnostic imaging , Biomarkers
17.
Bioact Mater ; 34: 366-380, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38269308

ABSTRACT

Oxidative stress, infection, and vasculopathy caused by hyperglycemia are the main barriers for the rapid repair of foot ulcers in patients with diabetes mellitus (DM). In recent times, the discovery of neddylation, a new type of post-translational modification, has been found to regulate various crucial biological processes including cell metabolism and the cell cycle. Nevertheless, its capacity to control the healing of wounds in diabetic patients remains unknown. This study shows that MLN49224, a compound that inhibits neddylation at low concentrations, enhances the healing of diabetic wounds by inhibiting the polarization of M1 macrophages and reducing the secretion of inflammatory factors. Moreover, it concurrently stimulates the growth, movement, and formation of blood vessel endothelial cells, leading to expedited healing of wounds in individuals with diabetes. The drug is loaded into biomimetic macrophage-membrane-coated PLGA nanoparticles (M-NPs/MLN4924). The membrane of macrophages shields nanoparticles from being eliminated in the reticuloendothelial system and counteracts the proinflammatory cytokines to alleviate inflammation in the surrounding area. The extended discharge of MLN4924 from M-NPs/MLN4924 stimulates the growth of endothelial cells and the formation of tubes, along with the polarization of macrophages towards the anti-inflammatory M2 phenotype. By loading M-NPs/MLN4924 into a hydrogel, the final formulation is able to meaningfully repair a diabetic wound, suggesting that M-NPs/MLN4924 is a promising engineered nanoplatform for tissue engineering.

18.
Sci Rep ; 14(1): 2213, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38278873

ABSTRACT

Field observations in sedimentation and erosion-prone areas indicate that most natural sand deposits may contain a certain amount of non-plastic fines and are often under anisotropic stress conditions. A series of triaxial compression tests were performed on clean and silty sand with fines content fc ranging from 0 to 20% at an initial mean effective stress of p0' = 100 kPa and varying consolidation conditions to understand the impact of initial stress anisotropy on undrained shear behavior. The results indicate that the state parameter ψ is a superior predictor for characterizing the responses of sand-fines mixtures compared to the global void ratio and relative density. A comparison of the behavior of clean and silty sand with a constant ψ (= - 0.03) confirms that the sample with 10% fc exhibits the strongest dilation and greatest shear resistance, irrespective of the consolidation conditions. It is also demonstrated that the initial stress anisotropy with a comparably higher static stress ratio ηs typically diminishes the shear strength of mixtures. However, the influence of initial stress anisotropy on soil stiffness is not unilateral. The sample consolidated to a negative ηs is stiffer than that under isotropic consolidation, while the presence of a positive ηs leads to a decrease in the secant Young's modulus.

19.
J Cardiovasc Comput Tomogr ; 18(2): 179-186, 2024.
Article in English | MEDLINE | ID: mdl-38262851

ABSTRACT

BACKGROUND: Quadricuspid aortic valve (QAV) is a rare congenital heart disease with a limited body of literature. This retrospective cohort study investigates QAV morphology, function, and clinical outcomes. METHODS: Echocardiography was used to assess valvular function. Morphological characteristics such as phenotypes, raphe, regurgitant orifice area (ROA), and aortic dilation (diameter >40 â€‹mm) were assessed by cardiac CT. Patients were followed up for the combined event of all-cause death and aortic valve replacement (AVR). RESULTS: Ninety QAV patients (screened from 322385 CT scans) were included (mean age 55.2 â€‹± â€‹13.6 years, 61.1 â€‹% male). Isolated significant aortic regurgitation (AR) was present in 75.6 â€‹% of patients. The cohort was dominated by type I (four equal leaflets, 37.8 â€‹%) and type II (3 larger and 1 smaller leaflets, 42.2 â€‹%) QAV. Fused raphe was present in 26.7 â€‹% of patients. ROACT was correlated with AR severity and aortic dilation (41.1 â€‹%, n â€‹= â€‹37). Among patients without AVR at baseline (n â€‹= â€‹60), one died and 17 underwent AVR during a median follow-up of 35.0 months (IQR:17.3-62.8). ROACT was associated with an increasing risk of combined event (as a categorical variable with a cut-off of 21.4 â€‹mm2, HR â€‹= â€‹4.25, 95%CI 1.49-12.17, p â€‹= â€‹0.007; as a continuous variable (per mm2 increment), HR â€‹= â€‹1.04, 95%CI 1.01-1.07, p â€‹= â€‹0.003). Additionally, ROACT had incremental prognostic value when added to the AR severity model (area under the receiver-operating characteristic curve increased from 86.8 to 88.4, p â€‹= â€‹0.004). CONCLUSION: QAV is characterized by variable anatomy, progressive AR, concomitant cusp fusion and aortic enlargement. ROACT may be a potential ancillary prognostic marker in patients with QAV.


Subject(s)
Aortic Diseases , Aortic Valve Insufficiency , Quadricuspid Aortic Valve , Humans , Male , Adult , Middle Aged , Aged , Female , Retrospective Studies , Predictive Value of Tests , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve/abnormalities , Aortic Valve Insufficiency/diagnostic imaging , Aortic Valve Insufficiency/etiology , Aortic Valve Insufficiency/surgery , Hemodynamics
20.
Chin Med J (Engl) ; 137(5): 588-595, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-37415525

ABSTRACT

BACKGROUND: Cerebrovascular disease (CVD) ranks among the foremost factors responsible for mortality on a global scale. The mortality patterns of CVDs and temporal trends in China need to be well-illustrated and updated. METHODS: We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention's Disease Surveillance Points (CDC-DSP) system. The mortality of CVD in 2020 was described by age, sex, residence, and region. The temporal trend from 2013 to 2019 was evaluated using joinpoint regression, and estimated rates of decline were extrapolated until 2030 using time series models. RESULTS: In 2019, the age-standardized mortality in China (ASMRC) per 100,000 individuals was 113.2. The ASMRC for males (137.7/10 5 ) and rural areas (123.0/10 5 ) were both higher when stratified by gender and urban/rural residence. The central region had the highest mortality (126.5/10 5 ), the western region had a slightly lower mortality (123.5/10 5 ), and the eastern region had the lowest mortality (97.3/10 5 ). The age-specific mortality showed an accelerated upward trend from aged 55-59 years, with maximum mortality observed in individuals over 85 years of age. The age-standardized mortality of CVD decreased by 2.43% (95% confidence interval, 1.02-3.81%) annually from 2013 to 2019. Notably, the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 years. In 2020, both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in 2019. The estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in 2030. CONCLUSION: The heightened focus on the burden of CVD among males, rural areas, the central and western of China, and individuals aged 75 years and above has emerged as a pivotal determinant in further decreasing mortalities, consequently presenting novel challenges to strategies for disease prevention and control.


Subject(s)
Cardiovascular Diseases , Cerebrovascular Disorders , Male , Humans , Aged, 80 and over , Urban Population , Cardiovascular Diseases/epidemiology , China/epidemiology , Rural Population
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