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Background: Accurate staging of liver fibrosis (LF) is essential for clinical management in chronic liver disease. While non-contrast MRI (NC-MRI) yields valuable information for liver assessment, its effectiveness in predicting LF remains underexplored. This study aimed to develop and validate artificial intelligence (AI)-powered models utilizing NC-MRI for staging LF. Methods: A total of 1726 patients from Shengjing Hospital of China Medical University, registered between October 2003 and October 2022, were retrospectively collected, and divided into development (n = 1208) and internal test (n = 518) cohorts. An external test cohort consisting of 337 individuals from six centers, registered between June 2015 and November 2022, were also included. All participants underwent NC-MRI (T1-weighted imaging, T1WI; and T2-fat-suppressed imaging, T2FS) and liver biopsies. Two classification models (CMs), named T1 and T2FS, were trained on respective image types using 3D contextual transformer networks and evaluated on both test cohorts. Additionally, three CMs-Clinic, Image, and Fusion-were developed using clinical features, T1 and T2FS scores, and their integration via logistic regression. Classification effectiveness of CMs was assessed using the area under the receiver operating characteristic curve (AUC). A comparison was conducted between the optimal models (OMs) with highest AUC and other methods (transient elastography, five serum biomarkers, and six radiologists). Findings: Fusion models (i.e., OM) yielded the highest AUC among the CMs, achieving AUCs of 0.810 for significant fibrosis, 0.881 for advanced fibrosis, and 0.918 for cirrhosis in the internal test cohort, and 0.808, 0.868, and 0.925, respectively, in the external test cohort. The OMs demonstrated superior performance in AUC, significantly surpassing transient elastography (only for staging ≥ F2 and ≥ F3 grades), serum biomarkers, and three junior radiologists for staging LF. Radiologists, with the aid of the OMs, can achieve a higher AUC in LF assessment. Interpretation: AI-powered models utilizing NC-MRI, including T1WI and T2FS, accurately stage LF. Funding: National Natural Science Foundation of China (No. 82071885); General Program of the Liaoning Provincial Department of Education (LJKMZ20221160); Liaoning Province Science and Technology Joint Plan (2023JH2/101700127); the Leading Young Talent Program of Xingliao Yingcai in Liaoning Province (XLYC2203037).
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The study is aimed to screen the differential expressed genes (DEGs) related to sperm DNA fragmentation in men and provide reference basis of the sperm selection in assisted reproduction based on DNA fragmentation. We evaluated 60 semen samples from patients with high, medium or low sperm DNA fragmentation index (DFI). Using multicolor flow cytometry, we measured the content of reactive oxygen species (ROS), phosphatidylserine (PS) externalization and mitochondrial membrane potential (MMP) in these sperm samples. The results revealed that the more ROS content and PS externalization were detected in the sperm with higher DFI, but there was lower MMP level in the high DFI sperm. Next, we conducted RNA sequencing (RNA-seq) on 3 groups of sperm samples with high, medium and low DFI. Then, Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed on DEGs. Furthermore, we utilized qRT-PCR to validated the significantly DEGs from the RNA-seq assay. The transcriptome results showed a total of 5334 DEGs were found in the sperm sample with high, medium and low DFI. According to GO and KEGG analysis 421 down-regulated genes in the high DFI group were related to oxidative stress and spermatogenesis. Thirteen novel genes were also identified that most likely were involved in sperm DNA fragmentation, which were further validated by qRT-PCR. In conclusion, our study suggested that the sperms with highly fragmented DNA were accompanied by down-regulation of a series of genes related to antioxidant and spermatogenesis.
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BACKGROUND: Pet-derived allergens are another source of indoor air pollution which could affect human health. However, the association between pet ownership and the risk of dry eye symptoms (DES) remains to be elucidated. METHODS: We conducted a nationwide cross-sectional survey among Chinese residents aged over 12 years from June 20, 2022 to August 31, 2022. The Ocular Surface Disease Index-6 (OSDI-6) questionnaire was utilized to evaluate the presence of DES. Multivariable logistic regression models were used to analyze the associations between pet ownership and DES. Subgroup analyses were conducted based on sex, age, residence and affective disorders, and sensitivity analysis by excluding participants with major ocular diseases. The interactions between pet ownership and other risk factors on DES were explored in the additive scale by calculating the synergy index (SI). RESULTS: A total of 21,916 subjects replied to the questionnaire. The prevalence of DES was 43.6 % (95 % confidence interval (CI), 43.0 %-44.3 %). Pet ownership was significantly associated with increased risk of DES (Odds ratio (OR): 1.13, 95%CI: 1.05-1.21), especially among the elderly (OR: 1.28, 95%CI: 1.09-1.51) and urban residents (OR: 1.13, 95%CI: 1.04-1.24). The individual effect of allergic rhinitis on DES was 2.59 (95%CI: 1.27-5.53), while the joint effect of pets and allergic rhinitis was 5.26 (95%CI: 1.20-36.74), suggesting a synergistic interaction with a SI of 2.48 (95%CI: 0.25-24.39). Furthermore, the interaction analysis also indicated a synergistic interaction between pet ownership and low health literacy with a SI of 1.12 (95%CI: 0.66-1.87). CONCLUSION: Pet ownership was identified as a risk factor for DES. The synergistic interaction of pet ownership and allergic rhinitis suggests shared mechanisms between DES and allergic conditions.
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Immune rejection caused by mismatches in human leucocyte antigens (HLAs) remains a major obstacle to the success of allogeneic cell therapies. Current strategies for the generation of 'universal' immune-compatible cells, particularly the editing of HLA class I (HLA-I) genes or the modulation of proteins that inhibit natural killer cells, often result in genomic instability or cellular cytotoxicity. Here we show that a ß2-microglobulin super-enhancer (B2M-SE) that is responsive to interferon-γ is a critical regulator of the expression of HLA-I on mesenchymal stromal cells (MSCs). Targeted epigenetic repression of B2M-SE in MSCs reduced the surface expression of HLA-I below the threshold required to activate allogenic T cells while maintaining levels sufficient to evade cytotoxicity mediated by natural killer cells. In a humanized mouse model, the epigenetically edited MSCs demonstrated improved survival by evading the immune system, allowing them to exert enhanced therapeutic effects on LPS-induced acute lung injury. Targeted epigenetic repression of B2M-SE may facilitate the development of off-the-shelf cell sources for allogeneic cell therapy.
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BACKGROUND: The best antiviral treatment for chronic hepatitis B (CHB) poses a complex challenge. The treatment effect of the combination of nucleoside analogues (NAs) and pegylated interferon alpha (PegIFN) was still in debate. METHODS: We studied patients treated with NAs and PegIFN-2b at our institution from November 2019 to January 2022. Logistic regression identified independent factors influencing clinical cure. The predictive accuracy of the formula was assessed using the Receiver operating characteristic (ROC) curve at different time points (before therapy, 12 weeks, and 24 weeks into treatment). RESULTS: A total of 120 patients were enrolled in the final analysis. Among the cohort of patients under study, 71 (59.1%) patients had clinical cure while 49 (40.9%) patients did not. Hepatitis B surface antigen (HBsAg) at baseline and age were the powerful variables predicting the clearance of HBsAg. The area under the ROC (AUC) was 0.907 for pre-treatment predictive model, 0.958 for 12-week predictive model and 0.747 for 24-week predictive model. CONCLUSION: This study provided predictive formulas for clinical cure, offering valuable insights for CHB treatment. PegIFN and NAs exhibited efficacy. Future research that explores additional factors, such as HBV genotype, in a larger cohort study is needed.
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Antivirais , Hepatite B Crônica , Interferon-alfa , Polietilenoglicóis , Proteínas Recombinantes , Humanos , Hepatite B Crônica/tratamento farmacológico , Masculino , Interferon-alfa/uso terapêutico , Antivirais/uso terapêutico , Feminino , Adulto , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Nucleosídeos/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Quimioterapia Combinada , Curva ROC , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Estudos Retrospectivos , Interferon alfa-2RESUMO
Vascular tissue engineering faces significant challenges in creating in vitro vascular disease models, implantable vascular grafts, and vascularized tissue/organ constructs due to limitations in manufacturing precision, structural complexity, replicating the composited architecture, and mimicking the mechanical properties of natural vessels. Light-based 3D bioprinting, leveraging the unique advantages of light including high resolution, rapid curing, multi-material adaptability, and tunable photochemistry, offers transformative solutions to these obstacles. With the emergence of diverse light-based 3D bioprinting techniques and innovative strategies, the advances in vascular tissue engineering have been significantly accelerated. This review provides an overview of the human vascular system and its physiological functions, followed by an in-depth discussion of advancements in light-based 3D bioprinting, including light-dominated and light-assisted techniques. We explore the application of these technologies in vascular tissue engineering for creating in vitro vascular disease models recapitulating key pathological features, implantable blood vessel grafts, and tissue analogs with the integration of capillary-like vasculatures. Finally, we provide readers with insights into the future perspectives of light-based 3D bioprinting to revolutionize vascular tissue engineering.
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The legacy of industry reflects a city's journey and marks its cultural essence, highlighting the significance of preserving and promoting such historical assets. There is a noticeable gap in the discourse surrounding the intrinsic value of industrial heritage attractions and their impact on the fidelity of tourists. In light of this, the present investigation, rooted in the ABC attitude framework, examines the linkage between the perceived value, contentment, and allegiance of initial visitors to these sites. The study delves into the intermediary function of contentment and the variable influence of gender. Focusing on the Maoming Open-pit Ecological Park as a case in point, this research gathered and scrutinized 320 valid questionnaires. The outcomes demonstrate that the perceived value exerts a positive effect on both the satisfaction and the steadfastness of tourists. Satisfaction is identified as an intermediary between perceived value and tourist steadfastness. Additionally, gender plays a notable role in moderating specific aspects of the model. This inquiry aids in harnessing the potential of industrial heritage sites for the advancement of tourism, fostering economic prosperity and the rebirth of cultural practices. Furthermore, it lays down essential theoretical and practical building blocks for the evolution of industrial heritage as a tourism asset.
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CONTEXT: Cardiometabolic multimorbidity (CM) is an increasing public health concern. Previous observational studies have suggested inverse associations between coffee, tea, and caffeine intake and risks of individual cardiometabolic diseases; however, their associations with CM and related biological markers are unknown. METHODS: This prospective study involved 172 315 (for caffeine analysis) and 188 091 (tea and coffee analysis) participants free of any cardiometabolic diseases at baseline from the UK Biobank; 168 metabolites were measured among 88 204 and 96 393 participants. CM was defined as the coexistence of at least 2 of the following conditions: type 2 diabetes, coronary heart disease, and stroke. RESULTS: Nonlinear inverse associations of coffee, tea, and caffeine intake with the risk of new-onset CM were observed. Compared with nonconsumers or consumers of less than 100â mg caffeine per day, consumers of moderate amount of coffee (3 drinks/d) or caffeine (200-300â mg/d) had the lowest risk for new-onset CM, with respective hazard ratios (95% CIs) of 0.519 (0.417-0.647) and 0.593 (0.499-0.704). Multistate models revealed that moderate coffee or caffeine intake was inversely associated with risks of almost all developmental stages of CM, including transitions from a disease-free state to single cardiometabolic diseases and subsequently to CM. A total of 80 to 97 metabolites, such as lipid components within very low-density lipoprotein, histidine, and glycoprotein acetyls, were identified to be associated with both coffee, tea, or caffeine intake and incident CM. CONCLUSION: Habitual coffee or caffeine intake, especially at a moderate level, was associated with a lower risk of new-onset CM and could play important roles in almost all transition phases of CM development. Future studies are warranted to validate the implicated metabolic biomarkers underlying the relation between coffee, tea, and caffeine intake and CM.
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PURPOSE: Current study aimed to understand the distribution and determinants of anterior chamber angle (ACA) and anterior chamber volume (ACV) in Chinese young adults, which can help fill current data gaps and aid in early detection and intervention for high-risk population of primary angle closure glaucoma. METHODS: This cross-sectional study utilized data from 2014 participants who completed questionnaire and eye examination in September 2021. ACV and ACA were measured using a Pentacam tomographer. Spherical equivalent (SE) was evaluated by autorefractor without cycloplegia. Central corneal thickness (CCT) and biomechanically corrected intraocular pressure (bIOP) were evaluated using Corvis-ST. Axial length (AL), corneal radius (CR), anterior chamber depth (ACD), and white to white were assessed using the IOL Master. RESULTS: A total of 1635 students were included in the analysis. The mean ACV and AVA were 194.74 ± 32.30 µL and 38.81 ± 4.84°, respectively. Males have a larger ACV and wider ACA than females. ACV was positively correlated with ACA (r = 0.24, p < 0.001), and the correlation was stronger for non-myopic students than for myopic students. Multivariable linear regression model showed that AL (ß = 2.41), CR (ß = -4.12), CCT (ß = -0.11), ACD (ß = 97.93), and bIOP (ß = 0.40) were associated with ACV, and CCT (ß = -0.01), CR (ß = 0.38), and ACD (ß = 7.41) were associated with ACA (all p < 0.05). Random forest model indicated that ACD was the most critical predictor of both ACV and ACA. CONCLUSIONS: This study reported the distribution and determinants of ACA and ACV. Deeper ACD was associated with larger ACV and wider ACA.
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Succinate is an important metabolite and a critical chemical with diverse applications in the food, pharmaceutical, and agriculture industries. Recent studies have demonstrated several protective or detrimental functions of succinate in diseases; however, the effect of succinate on lipid metabolism is still unclear. Here, we identified a role of succinate in nonobese nonalcoholic fatty liver disease (NAFLD). Specifically, the level of succinate is increased in the livers and serum of mice with hepatic steatosis. The administration of succinate promotes triglyceride (TG) deposition and hepatic steatosis by suppressing fatty acid oxidation (FAO) in nonobese NAFLD mouse models. RNA-Seq revealed that succinate suppressed fibroblast growth factor 21 (FGF21) expression. Then, the restoration of FGF21 was sufficient to alleviate hepatic steatosis and FAO inhibition induced by succinate treatment in vitro and in vivo. Furthermore, the inhibition of FGF21 expression and FAO mediated by succinate was dependent on the AMPK/PPARα axis. This study provides evidence linking succinate exposure to abnormal hepatic lipid metabolism and the progression of nonobese NAFLD.
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Proteínas Quinases Ativadas por AMP , Ácidos Graxos , Fatores de Crescimento de Fibroblastos , Fígado , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica , Oxirredução , PPAR alfa , Ácido Succínico , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , PPAR alfa/metabolismo , PPAR alfa/genética , Camundongos , Masculino , Ácidos Graxos/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Humanos , Ácido Succínico/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado Gorduroso/metabolismo , Fígado Gorduroso/genéticaRESUMO
BACKGROUND: Digital public health (DiPH) interventions may help us tackle substantial public health challenges and reach historically underserved populations, in addition to presenting valuable opportunities to improve and complement existing services. However, DiPH interventions are often triggered through technological advancements and opportunities rather than public health needs. To develop and evaluate interventions designed to serve public health needs, a comprehensive framework is needed that systematically covers all aspects with relevance for public health. This includes considering the complexity of the technology, the context in which the technology is supposed to operate, its implementation, and its effects on public health, including ethical, legal, and social aspects. OBJECTIVE: We aimed to develop such a DiPH framework with a comprehensive list of core principles to be considered throughout the development and evaluation process of any DiPH intervention. METHODS: The resulting digital public health framework (DigiPHrame) was based on a scoping review of existing digital health and public health frameworks. After extracting all assessment criteria from these frameworks, we clustered the criteria. During a series of multidisciplinary meetings with experts from the Leibniz ScienceCampus Digital Public Health, we restructured each domain to represent the complexity of DiPH. In this paper, we used a COVID-19 contact-tracing app as a use case to illustrate how DigiPHrame may be applied to assess DiPH interventions. RESULTS: The current version of DigiPHrame consists of 182 questions nested under 12 domains. Domain 1 describes the current status of health needs and existing interventions; domains 2 and 3, the DiPH technology under assessment and aspects related to human-computer interaction, respectively; domains 4 and 5, structural and process aspects, respectively; and domains 6-12, contextual conditions and the outcomes of the DiPH intervention from broad perspectives. In the CWA use case, a number of questions relevant during its development but also important for assessors once the CWA was available were highlighted. CONCLUSIONS: DigiPHrame is a comprehensive framework for the development and assessment of digital technologies designed for public health purposes. It is a living framework and will, therefore, be updated regularly and as new public health needs and technological advancements emerge.
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COVID-19 , Saúde Pública , Humanos , Saúde Pública/métodos , COVID-19/prevenção & controle , COVID-19/epidemiologia , TelemedicinaRESUMO
PURPOSE: Breast cancer diagnosis often presents patients with complex treatment decisions, particularly concerning surgical options. A patient decision aid can assist patients in making better decisions, and ultimately improving health outcomes positively. This study aims to explore the perceptions and needs of breast cancer patients regarding the utilization of wed-based surgical decision aids. METHODS: A descriptive qualitative study was conducted using semi-structured interviews with purposive sampling that were audio recorded and transcribed verbatim. A thematic analysis was conducted using NVivo 12 software. Participants were recruited from a tertiary general hospital in Shanghai, China. Inclusion criteria were being diagnosed with breast cancer, age over 18 years old, considering breast cancer surgery as a treatment option and able/willing to give informed consent. RESULTS: From March to May 2023, 16 patients consented to participate and completed the interviews. Three major themes were revealed, with corresponding sub-themes: (1) informative and useful content (need to know as much information as possible, easy to understand and presented in multiple ways and highly credible from reliable resource); (2) user-friendly on design (easy to operate, simple function and man-machine interaction); and (3) suggested timing of use. CONCLUSIONS: Patients' perspectives and needs about wed-based surgical decision aids are numerous and diverse. In designing wed-based surgical decision aids for breast cancer patients, content, design and timing are all factors that need to be taken into consideration to encourage informed surgical decisions. Further work will focus on developing a feasible and acceptable web-based surgical patient decision aid (PtDA), and test its usability in a clinical setting to understand if the PtDA can meet the decisional needs of breast cancer patients, thus to improve quality of decision-making.
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Neoplasias da Mama , Técnicas de Apoio para a Decisão , Pesquisa Qualitativa , Humanos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/psicologia , Feminino , Pessoa de Meia-Idade , Adulto , China , Idoso , Mastectomia , Avaliação das Necessidades , Tomada de Decisões , Participação do Paciente/psicologiaRESUMO
PURPOSE: Animal models suggest omega-3 polyunsaturated fatty acids (PUFAs) may protect against myopia by modulating choroidal blood perfusion, but clinical evidence is scarce and mixed. We aimed to determine the causality between omega-3 PUFAs and myopia using Mendelian randomization (MR) analysis. DESIGN: Two-sample MR analysis. METHODS: Exposures are genetically predicted plasma levels of 18 fatty acid (FA)-related traits. Spherical equivalent refraction (SER) and axial length were used as measurements of myopia. Genome-wide association study summary data on plasma levels of 18 FA-related traits (n=115,006), refractive spherical equivalent (n=351,091), axial length (n=69,945), and choroidal thickness (n=44,823) were sourced from the UK Biobank, the Genetic Epidemiology Research on Adult Health and Aging cohort, and the Consortium for Refractive Error and Myopia Study. We used 5 MR models and considered results statistically significant if the Bonferroni-corrected P value was ≤2.78 ×10-3 in at least 3 MR models. The ß represents the change in outcomes (SER in diopters; axial length in millimeters; and choroidal thickness in SD) per SD unit increase in FA levels. RESULTS: At a Bonferroni-corrected significance, higher levels of omega-3 (ß, 0.32-0.34), omega-3-total FA ratio (ß, 0.31-0.44), docosahexaenoic acid (DHA) (ß, 0.36-0.46), DHA-total FA ratio (ß, 0.37-0.53), PUFA-total FA ratio (ß, 0.07-1.003), and degree of unsaturation (ß, 0.28-0.44) were associated with a more positive SER, suggesting a lower risk of myopia. Similar trends were observed for axial length albeit with borderline significance (P ≤ .035 in ≥2 models). Higher levels of omega-3, DHA, DHA-total FA ratio, PUFA-total FA ratio, PUFA-monounsaturated FA ratio, and degree of unsaturation were nominally associated with thicker choroidal thickness (ß, 0.05-0.13; P ≤ .045 in ≥2 models). CONCLUSION: Our multiple MR models suggest a protective effect of omega-3 and DHA on myopia, potentially through modulation of choroidal blood perfusion. Further randomized clinical trials are needed to confirm the effectiveness and determine the optimal dose and duration.
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Background: Personality has an impact on the health-related quality of life (HRQoL) of older adults. However, the relationship and mechanisms of the 2 variables are controversial, and few studies have been conducted on older adults. Objective: The aim of this study was to explore the relationship between personality and HRQoL and the mediating and moderating roles of sleep quality and place of residence in this relationship. Methods: A total of 4123 adults 60 years and older were from the Psychology and Behavior Investigation of Chinese Residents survey. Participants were asked to complete the Big Five Inventory, the Brief version of the Pittsburgh Sleep Quality Index, and EQ-5D-5L. A backpropagation neural network was used to explore the order of factors contributing to HRQoL. Path analysis was performed to evaluate the mediation hypothesis. Results: As of August 31, 2022, we enrolled 4123 older adults 60 years and older. Neuroticism and extraversion were strong influencing factors of HRQoL (normalized importance >50%). The results of the mediation analysis suggested that neuroticism and extraversion may enhance and diminish, respectively, HRQoL (index: ß=-.262, P<.001; visual analog scale: ß=-.193, P<.001) by increasing and decreasing brief version of the Pittsburgh Sleep Quality Index scores (neuroticism: ß=.17, P<.001; extraversion: ß=-.069, P<.001). The multigroup analysis suggested a significant moderating effect of the place of residence (EQ-5D-5L index: P<.001; EQ-5D-5L visual analog scale: P<.001). No significant direct effect was observed between extraversion and EQ-5D-5L index in urban older residents (ß=.037, P=.73). Conclusions: This study sheds light on the potential mechanisms of personality and HRQoL among older Chinese adults and can help health care providers and relevant departments take reasonable measures to promote healthy aging.
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Personalidade , Qualidade de Vida , Humanos , Masculino , Estudos Transversais , Qualidade de Vida/psicologia , Feminino , Idoso , China/epidemiologia , Pessoa de Meia-Idade , Análise de Mediação , Idoso de 80 Anos ou mais , Inquéritos e Questionários , Qualidade do Sono , População do Leste AsiáticoRESUMO
PURPOSE: Radiation cystitis (RC) is a complex and common complication after radiotherapy for pelvic cancer. Icariside II (ICAII) is a flavonoid compound extracted from Epimedium, a traditional Chinese medicine, with various pharmacological activities. The aim of the present study was to investigate the cysto-protective effects of ICAII in RC rats and its possible mechanisms. MATERIALS AND METHODS: A rat model of induced radiation cystitis using pelvic X-ray irradiation was used, and bladder function was assessed by bladder volume and bladder leakage point pressure (LPP) after ICAII treatment. HE and Masson stains were used to assess the histopathological changes in the bladder. IL-6, TNF-α, IL-10, IL-4 and IL-1ß were measured by ELISA to assess the level of inflammation. The gene-level changes in ICAII-treated RC were observed by transcriptome sequencing, and then the potential targets of action and biological mechanisms were explored by PPI, GO and KEGG enrichment analysis of the differentially expressed genes. Finally, the predicted targets of action were experimentally validated using immunohistochemistry, RT-qPCR, molecular docking and CETSA. RESULTS: ICAII significantly increased bladder volume and the LPP, ameliorated pathological damage to bladder tissues, decreased the levels of IL-6, TNF-α, and IL-1ß, and increased the levels of IL-10 and IL-4 in radiation-injured rats. A total of 90 differentially expressed genes were obtained by transcriptome sequencing, and PPI analysis identified H3F3C, ISG15, SPP1, and LCN2 as possible potential targets of action. GO and KEGG analyses revealed that these differentially expressed genes were mainly enriched in the pathways metabolism of xenobiotics by cytochrome P450, arachidonic acid metabolism, Staphylococcus aureus infection and chemical carcinogenesis - reactive oxygen species. Experimental validation showed that ICAII could significantly increase the expression of H3F3C and ISG15 and inhibit the expression of SPP1 and LCN2. ICAII binds well to H3F3C, ISG15, SPP1 and LCN2, with the best binding ability to H3F3C. Furthermore, ICAII inhibited the protein degradation of H3F3C in bladder epithelial cells. CONCLUSIONS: ICAII may alleviate the bladder inflammatory response and inhibit the fibrosis process of bladder tissues through the regulation of H3F3C, ISG15, SPP1, and LCN2 targets and has a protective effect on the bladder of radioinjured rats. In particular, H3F3C may be one of the most promising therapeutic targets.
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Cistite , Flavonoides , Bexiga Urinária , Animais , Ratos , Cistite/induzido quimicamente , Cistite/metabolismo , Cistite/prevenção & controle , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/efeitos da radiação , Bexiga Urinária/patologia , Bexiga Urinária/metabolismo , Flavonoides/farmacologia , Ratos Sprague-Dawley , Feminino , Transcriptoma/efeitos dos fármacos , Protetores contra Radiação/farmacologia , Modelos Animais de Doenças , Citocinas/metabolismo , Simulação de Acoplamento MolecularRESUMO
BACKGROUND: Due to the high prevalence of multimorbidity and realistic health service demands for fall prevention, there is growing interest in the association between multimorbidity and falls. Our study aimed to identify multimorbidity patterns among Chinese older adults and explore the association between multimorbidity patterns and falls. METHODS: Data from 4,579 Chinese community-dwelling older adults was included in this analysis. Information regarding falls and 10 chronic conditions was collected. An exploratory factor analysis was performed to determine multimorbidity patterns. Regression models were fitted to explore the associations of individual chronic disease or multimorbidity patterns with falls. RESULTS: Among 4,579 participants, 368 (8.0%) were defined as fallers, including 92 (2.0%) frequent fallers, and multimorbidity affected 2,503 (54.7%) participants. Older adults with multimorbidity were more likely to be fallers [odds ratio (OR) = 1.3, P = 0.02] and frequent fallers (OR = 1.7, P = 0.04). Three multimorbidity patterns were identified (i.e., cardiovascular-metabolic diseases, psycho-cognitive diseases and organic diseases), and the associations between psycho-cognitive diseases/organic diseases and prevalent falls or frequent falls were found to be significant. CONCLUSIONS: The psycho-cognitive disease pattern and organic disease pattern are significantly associated with falls. Therefore, more attention should be paid to patients with psycho-cognitive diseases and timely, targeted diagnostic and treatment services should be provided in fall prevention.
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Acidentes por Quedas , Vida Independente , Multimorbidade , Humanos , Acidentes por Quedas/prevenção & controle , Masculino , Idoso , Feminino , Multimorbidade/tendências , China/epidemiologia , Idoso de 80 Anos ou mais , Vida Independente/tendências , Fatores de Risco , Estudos Transversais , Doença Crônica/epidemiologiaRESUMO
Aging is identified as a significant risk factor for severe coronavirus disease-2019 (COVID-19), often resulting in profound lung damage and mortality. Yet, the biological relationship between aging, aging-related comorbidities, and COVID-19 remains incompletely understood. This study aimed to elucidate the age-related COVID19 pathogenesis using an Hutchinson-Gilford progeria syndrome (HGPS) mouse model, a premature aging disease model, with humanized ACE2 receptors. Pathological features were compared between young, aged, and HGPS hACE2 mice following SARS-CoV-2 challenge. We demonstrated that young mice display robust interferon response and antiviral activity, whereas this response is attenuated in aged mice. Viral infection in aged mice results in severe respiratory tract hemorrhage, likely contributing a higher mortality rate. In contrast, HGPS hACE2 mice exhibit milder disease manifestations characterized by minor immune cell infiltration and dysregulation of multiple metabolic processes. Comprehensive transcriptome analysis revealed both shared and unique gene expression dynamics among different mouse groups. Collectively, our studies evaluated the impact of SARS-CoV-2 infection on progeroid syndromes using a HGPS hACE2 mouse model, which holds promise as a useful tool for investigating COVID-19 pathogenesis in individuals with premature aging.
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Senilidade Prematura , Enzima de Conversão de Angiotensina 2 , COVID-19 , Modelos Animais de Doenças , Progéria , SARS-CoV-2 , Animais , COVID-19/virologia , COVID-19/patologia , Senilidade Prematura/virologia , Senilidade Prematura/genética , Camundongos , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , SARS-CoV-2/patogenicidade , Progéria/genética , Progéria/patologia , Humanos , Pulmão/patologia , Pulmão/virologia , FemininoRESUMO
What is already known about this topic?: Previously, it has been proved that a simplified model that uses refraction error value provides a robust and efficient means of predicting myopia for non-myopic students. Intervention targeting non-myopic children with alert refraction errors (or insufficient hyperopia reserve) holds significant importance in reducing the incidence rate of myopia. What is added by this report?: This study, comprising two phases (surveillance and cohort studies), was aiming to pinpoint the precise refractive error value for the onset of myopia prediction among non-myopic children in Jiangsu Province. What are the implications for public health practice?: First, when conducting myopia screenings using pupil dilation for non-myopic populations: the cycloplegic 50th percentile refractive error emerges as a more precise predictive indicator. Second, when conducting myopia screenings without pupil dilation: this study advocates for the incorporation of axial length (AL) and corneal curvature (CC) values as supplementary indicators in screenings.
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BACKGROUND/AIMS: Animal models have shown that the absence of high-frequency visual information can precipitate the onset of myopia, but this relationship remains unclear in humans. This study aims to explore the association between the spatial frequency content of the visual environment and myopia in children. METHODS: Images from the rooms of children and their frequently visited outdoor areas were taken by their parents and collected by the researcher through questionnaires. The spatial frequency was quantified using Matlab. Cycloplegic refraction was used to measure the spherical equivalent (SE), and IOL Master was used to measure axial length (AL) and corneal radius (CR). AL/CR ratio was calculated. RESULTS: The study included 566 children with an average age of (8.04±1.47) years, of which 270 were girls (47.7%), and the average SE was (0.70±1.21) D. Image analysis revealed that indoor spatial frequency slope was lower than that of the outdoor environment (-1.43±0.18 vs -1.11±0.23, p<0.001). There were 79 myopic individuals (14.0%). Images from indoor content of myopic children had a lower spatial frequency slope than non-myopic children (-1.47±0.16 vs 1.43±0.18, p=0.03) while there was no significant difference in outdoor spatial frequency slope. Regression analysis indicated that the indoor spatial frequency slope was positively associated with SE value (ß=0.60, p=0.02) and inversely related to myopia (OR=0.24, p<0.05). CONCLUSION: The spatial frequency of the outdoor environment is significantly higher than that of the indoor environment. Indoor spatial frequency is related to children's refractive status, with lower indoor spatial frequency being associated with a higher degree of myopia.