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BACKGROUND: Helicobacter pylori (HP), the most common pathogenic microorganism in the stomach, can induce inflammatory reactions in the gastric mucosa, causing chronic gastritis and even gastric cancer. HP infection affects over 4.4 billion people globally, with a worldwide infection rate of up to 50%. The multidrug resistance of HP poses a serious challenge to eradication. It has been de-monstrated that compared to bismuth quadruple therapy, Qingre Huashi decoction (QHD) combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions; in addition, QHD can directly inhibit and kill HP in vitro. AIM: To explore the effect and mechanism of QHD on clinically multidrug-resistant and strong biofilm-forming HP. METHODS: In this study, 12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients. In vitro, the minimum inhibitory concentration (MIC) values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining, respectively. The most robust biofilm-forming strain of HP was selected, and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation. This assessment was performed using agar dilution, E-test, killing dynamics, and transmission electron microscopy (TEM). The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation. Crystalline violet method, scanning electron microscopy, laser confocal scanning microscopy, and (p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains. The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction. Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups. RESULTS: HP could form biofilms of different degrees in vitro, and the intensity of formation was associated with the drug resistance of the strain. QHD had strong bacteriostatic and bactericidal effects on HP, with MICs of 32-64 mg/mL. QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains, disrupt the biofilm structure, lower the accumulation of (p)ppGpp, decrease the expression of biofilm-related genes including LuxS, Spot, glup (HP1174), NapA, and CagE, and reduce the expression of efflux pump-related genes such as HP0605, HP0971, HP1327, and HP1489. Based on metabolomic analysis, QHD induced oxidative stress in HP, enhanced metabolism, and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate (AMP), thereby affecting HP growth, metabolism, and protein synthesis. CONCLUSION: QHD exerts bacteriostatic and bactericidal effects on HP, and reduces HP drug resistance by inhibiting HP biofilm formation, destroying its biofilm structure, inhibiting the expression of biofilm-related genes and efflux pump-related genes, enhancing HP metabolism, and activating AMP in HP.
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Antibacterianos , Biopelículas , Medicamentos Herbarios Chinos , Infecciones por Helicobacter , Helicobacter pylori , Pruebas de Sensibilidad Microbiana , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/aislamiento & purificación , Biopelículas/efectos de los fármacos , Humanos , Medicamentos Herbarios Chinos/farmacología , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , GastroscopíaRESUMEN
BACKGROUND: Anorexia of aging (AA) is a common geriatric syndrome that seriously endangers the health of older adults. Early identification of populations at risk of AAand the implementation of appropriate intervention measures hold significant public health importance. This study aimed to develop a nomogram for predicting the risk of AA among older people. METHODS: We conducted a cross-sectional study involving 2144 community-dwelling older adults to evaluate the AA using the Simplified Nutritional Appetite Questionnaire. We utilized the Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis to select variables and develop a nomogram prediction model. The predictive performance of the nomogram was evaluated using the Receiver Operating Characteristic (ROC) curves, calibration curves, Decision Curve Analysis (DCA), and internal validation. RESULTS: The prevalence of AA among Chinese older adults was 21.7% (95%CI: 20.0%-23.5%). Age, sex, family economic level, smoking status, dysphagia, loneliness, depressive symptoms, living alone, health literacy, life satisfaction, and body mass index have been identified as predictive factors for AA among older people. The nomogram constructed based on these predictive factors showed an area under the curve (AUC) of 0.766 (95%CI: 0.742-0.791), indicating good calibration and discrimination ability. Additionally, the results obtained from the 10-fold cross-validation process confirmed the nomogram's good predictive capabilities. Furthermore, the DCA results showed that the nomogram has clinical utility. CONCLUSION: The nomogram constructed in this study serves as an effective tool for predicting anorexia of aging among community-dwelling older adults. Its implementation can help community healthcare workers evaluate the risk of AA in this population and identify high-risk groups.
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The diverse properties reported for starch-based materials indicate their potential for use in the preparation of biodegradable flexible actuators. However, their natural brittleness and lack of durability after modification limit their practical application. Therefore, we propose a strategy for preparing flexible starch-based composites. The results of macro/micro property characterizations and molecular dynamics simulations indicated that using starch, maleic anhydride, and stearic acid (SA), the mobility of the starch chains was enhanced and retrogradation was inhibited through the synergistic effects induced by chain breaking, complex formation with SA, and esterification of the starch molecules. In addition, the elongation at break of the modified starch (MS) reached 2070 %, and considerable ductility (>1000 %) as well as well-complexed structure were maintained after six months. Furthermore, the MS was able to undergo self-healing after fracture or a temperature-controlled stiffness transition. Moreover, it underwent complete degradation in soil within 30 d. Finally, an actuator was prepared by doping the MS with nano-Fe3O4 particles to realize a dual magnetic and optical response. Dynamic monitoring was also achieved based on the electrical signal, thereby demonstrating the broad application scope of this material in the development of biodegradable flexible actuators.
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The fabrication of antifouling zwitterionic polymer brushes represents a leading approach to mitigate nonspecific adhesion on the surfaces of medical devices. This investigation seeks to elucidate the correlation between the material composition and structural attributes of these polymer brushes in preventing protein adhesion. To achieve this goal, we modeled three different zwitterionic brushes, namely, carboxybetaine methacrylate (CBMA), sulfobetaine methacrylate (SBMA), and (2-(methacryloyloxy)ethyl)-phosphorylcholine (MPC). The simulations revealed that elevating the grafting density enhances the structural stability, hydration strength, and resistance to protein adhesion exhibited by the polymer brushes. PCBMA manifests a more robust hydration layer, while PMPC demonstrates the slightest interaction with proteins. In a comprehensive evaluation, PSBMA polymer brushes emerged as the best choice with superior stability, enhanced protein repulsion, and minimally induced protein deformation, resulting in effective resistance to nonspecific adhesion. The high-density SBMA polymer brushes significantly reduce the level of protein adhesion in AFM testing. In addition, we have pioneered the quantitative characterization of hydration repulsion in polymer brushes by analyzing the hydration repulsion characteristics at different materials and graft densities. In summary, our study provides a nuanced understanding of the material and structural determinants influencing the capacity of zwitterionic polymer brushes to thwart protein adhesion. Additionally, it presents a quantitative elucidation of hydration repulsion, contributing to the advancement and application of antifouling polymer brushes.
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Polímeros , Proteínas , Polímeros/química , Fenómenos Físicos , Adsorción , Metacrilatos/químicaRESUMEN
Inflammatory bowel disease (IBD) and atherosclerosis (AS) are both common chronic inflammatory diseases with similar pathophysiological mechanisms. Some studies have shown that IBD patients are at increased risk for early atherosclerosis, myocardial infarction and venous thrombosis. Here we set up a hybrid mouse model associated with atherosclerosis and acute colitis in order to investigate the interplay of the two diseases. We fed ApoE-/- mice with high fat diet to establish atherosclerosis model, and used animal ultrasound machine to detect the artery of mice noninvasively. Then a new hybrid model of atherosclerosis and acute colitis was prepared by drinking water for 7 days. At the end of the experiment, the hybrid model mice showed typically pathological and intuitionistic changes of atherosclerosis and acute colitis. We found the shortened colon length, high histopathological scores of the colon with mucosal erosion and necrosis, hyperlipidemia, a plaque-covered mouse aorta and plaque with foam cells and lipid deposition in the hybrid model group, which proved that the hybrid model was successfully established. At the same time, ultrasonic detection showed that the end-diastolic blood flow velocity and the relative dilation value were decreased, while systolic time / diastolic time, the wall thickness, systolic diameters as well as diastolic diameters were gradually increased, and statistical significance appeared as early as 8 weeks. We clearly described the process of establishing a hybrid model of atherosclerosis and acute colitis, which might provide a repeatable platform for the interaction mechanism exploring and drug screening of atherosclerosis and inflammatory bowel disease in preclinical study.
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Aterosclerosis , Colitis , Enfermedades Inflamatorias del Intestino , Placa Aterosclerótica , Humanos , Ratones , Animales , Ratones Noqueados , Ratones Noqueados para ApoE , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/genética , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/complicaciones , Dieta Alta en Grasa/efectos adversos , Apolipoproteínas E/genética , Colitis/complicaciones , Enfermedades Inflamatorias del Intestino/complicaciones , Ratones Endogámicos C57BL , Modelos Animales de EnfermedadRESUMEN
Human induced pluripotent stem cells (hiPSCs) have been regarded as a potential stem cell source for cell therapy. However, the production of cells with mesenchymal potential from hiPSCs through spontaneous differentiation is time consuming and laborious. In the present study, the combined use of the GSK-3 inhibitor CHIR99021 and TGF-ß was used to obtain mesenchymal stem cell (MSC)-like cells from hiPSCs. During the induction process, the transcription of epithelial-mesenchymal transition (EMT)-related genes N-cadherin and Vimentin in the transformed cells was upregulated, whereas the transcription of E-cadherin and pluripotency-related transcription factors SOX2, OCT4 and NANOG did not change significantly. This indicated that whilst cells were pluripotent, EMT was initiated by the upregulation of transcription of EMT promoting genes. Both SMAD-dependent and independent signalling pathways were significantly activated by the combined induction treatment compared with the single factor induction. The hiPSC-derived MSC-like cells (hiPSC-MSCs) expressed MSC-related markers and acquired osteogenic, chondrogenic and adipogenic differentiation potentials. After being injected into the peritoneal cavity of rats, the hiPSC-MSCs secreted angiogenic and immune-regulatory factors and remained on the colicomentum for 3 weeks. Within an 11-week period, four intraperitoneal hiPSC-MSC injections (1x107 cells/injection) into acute myocardial infarction (AMI) model rats significantly increased the left ventricular ejection fraction, left ventricular fractional shortening and angiogenesis and significantly reduced scar size and the extent of apoptosis in the infarcted area compared with that of the control PBS injection. Symptoms of hiPSC-MSC-induced immune reaction or tumour formation were not observed over the course of the experiment in the hiSPC-MSC treated rats. In conclusion, the CHIR99021 and TGF-ß combined induction was a rapid and effective method to obtain MSC-like cells from hiPSCs and multiple high dose intraperitoneal injections of hiPSC-derived MSCs were safe and effective at restoring cardiac function in an AMI rat model.
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BACKGROUND: This study aimed to explore the associations between household air pollution (HAP), measured by cooking fuel use, sensory impairments (SI), and their transitions in Chinese middle-aged and older adults. METHODS: Participants were recruited from the 2011 China Health and Retirement Longitudinal Study (CHARLS) and were subsequently followed up until 2018. Data on SI were collected by self-reported hearing and vision impairments, which were divided into three categories: non-SI, single SI (hearing or vision impairment), and dual SI (DSI). Cooking fuels, including solid and clean fuels, are proxies for HAP. The transitions of cooking fuels and SI refer to the switching of the fuel type or SI status from baseline to follow-up. Cox proportional hazard regression models were used to explore associations, and hazard ratios (HRs) and 95% confidence intervals (CI) were used to evaluate the strength of the association. RESULTS: The prevalence of non-SI, single SI, and DSI was 59.6%, 31.8%, and 8.6%, respectively, among the 15,643 participants at baseline in this study. Over a median follow-up of 7.0 years, 5,223 worsening SI transitions were observed. In the fully adjusted model, solid fuel use for cooking was associated with a higher risk of worsening SI transitions, including from non-SI to single SI (HR = 1.08, 95% CI = 1.01-1.16) and from non-SI to DSI (HR = 1.26, 95% CI = 1.09-1.47), but not from single SI to DSI. In addition, compared to those who always used solid fuels, participants who switched from solid to clean fuel for cooking appeared to have attenuated the risk of worsening SI transitions. The statistical significance of the associations remained in the set of sensitivity analyses. CONCLUSION: Solid fuel use was associated with higher risks of worsening SI transitions, while converting the type of cooking fuel from solid to clean fuels may reduce the risk of worsening SI transitions. Our study suggests that tailored clean fuel interventions, especially in developing countries, should be implemented to prevent sensory impairments and hence reduce the burden of sensory impairment-related disability.
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Culinaria , Humanos , Persona de Mediana Edad , Anciano , Estudios de Cohortes , Factores de Riesgo , Estudios Longitudinales , Estudios Prospectivos , China/epidemiologíaRESUMEN
Background and Objectives: Housing is one of the main places where falls occur; however, few studies have examined housing environmental factors driving fall risk. This study aimed to explore the associations between housing environmental factors and falls in China. Research Design and Methods: The study included data of middle-aged and older adults aged ≥45 years from 4 waves of the China Health and Retirement Longitudinal Study. We assessed 7 housing environmental factors: building materials, toilet types, household tidiness, household cooking fuels, and access to electricity, running water, and bathing facilities. Based on these, we divided housing environments into 3 types: good (0-2 poor factors), moderate (3-5 poor factors), and poor (6-7 poor factors). Falls incidence (yes or no) was self-reported during the survey period. We applied the Cox proportional hazard model to estimate the associations, adjusting for a set of covariates such as sociodemographic characteristics, lifestyles, and disease status. Results: A total of 12,382 participants were analyzed, and the incidence of falls was 31.7%. According to the fully adjusted model, having a squatting toilet (hazard ratio [HR]â =â 1.14, 95% confidence interval [CI]â =â 1.03-1.26), household untidiness (HRâ =â 1.09, 95% CIâ =â 1.01-1.18), and solid fuel use for cooking (HRâ =â 1.10, 95% CIâ =â 1.02-1.18) were associated with a higher risk of falls (psâ <â .05), compared to their counterparts. We found a linear relationship between housing environments and falls (p for trendâ =â .001). Specifically, moderate (HRâ =â 1.16, 95% CIâ =â 1.06-1.27) and poor housing environments (HRâ =â 1.21, 95% CIâ =â 1.08-1.34) were associated with a higher risk of falls compared to a good housing environment. Discussion and Implications: Among middle-aged and older Chinese adults, a better household environment, including sitting toilets, tidy living conditions, and clean fuel use for cooking, may reduce the risk of falls. The evidence from our study suggests the need to implement age-friendly housing environments to prevent falls and disability in an aging society.
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Observational studies have shown that the gut microbiome is associated with frailty. However, whether these associations underlie causal effects remains unknown. Thus, this study aimed to assess the genetic correlation and causal relationships between the genetically predicted gut microbiome and frailty using linkage disequilibrium score regression (LDSC) and Mendelian Randomization (MR). Summary statistics for the gut microbiome were obtained from a genome-wide association study (GWAS) meta-analysis of the MiBioGen consortium (N = 18,340). Summary statistics for frailty were obtained from a GWAS meta-analysis, including the UK Biobank and TwinGene (N = 175,226). We used LDSC and MR analyses to estimate the genetic correlation and causality between the genetically predicted gut microbiome and frailty. Our findings indicate a suggestive genetic correlation between Christensenellaceae R-7 and frailty. Moreover, we found evidence for suggestive causal effects of twelve genus-level gut microbes on frailty using at least two MR methods. There was no evidence of horizontal pleiotropy or heterogeneity in the MR analysis. This study provides suggestive evidence for a potential genetic correlation and causal association between several genetically predicted gut microbes and frailty. More population-based observational studies and animal experiments are required to clarify this association and the underlying mechanisms.
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Fragilidad , Microbioma Gastrointestinal , Fragilidad/genética , Microbioma Gastrointestinal/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , HumanosRESUMEN
The CRISPR-Cas systems have been widely used as genome editing tools, with type II and V systems typically introducing small indels, and type I system mediating long-range deletions. However, the precision of type I systems for large fragment deletion is still remained to be optimized. Here, we developed a compact Cascade-Cas3 Dvu I-C system with Cas11c for plant genome editing. The Dvu I-C system was efficient to introduce controllable large fragment deletion up to at least 20 kb using paired crRNAs. The paired-crRNAs design also improved the controllability of deletions for the type I-E system. Dvu I-C system was sensitive to spacer length and mismatch, which was benefit for target specificity. In addition, we showed that the Dvu I-C system was efficient for generating stable transgenic lines in maize and rice with the editing efficiency up to 86.67%. Overall, Dvu I-C system we developed here is powerful for achieving controllable large fragment deletions.
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Sistemas CRISPR-Cas , Edición Génica , Sistemas CRISPR-Cas/genética , Plantas/genética , Genoma de Planta , Mutación INDELRESUMEN
Objectives: Patients with digestive diseases frequently suffer from dyspepsia and malabsorption, which may lead to muscle loss due to malnutrition. However, it is not clear whether digestive diseases are associated with sarcopenia. This study aims to explore the longitudinal association between digestive diseases and sarcopenia in middle-aged and older adults based on a nationally representative survey from China. Methods: We used a prospective cohort study including 7,025 middle-aged and older adults aged ≥45 years from the 2011 to 2015 waves China Health and Retirement Longitudinal Study (CHARLS). Digestive diseases were identified using self-report. The assessment of sarcopenia was based on the Asian Working Group for Sarcopenia 2019 Consensus and included three components of muscle strength, physical performance, and muscle mass. Cox hazards regression was used to examine the association between digestive diseases and sarcopenia. Results: The prevalence of digestive diseases and the incidence of sarcopenia in middle-aged and older adults were 22.6% (95% CI = 21.6-23.6%) and 8.5% (95% CI = 7.8-9.1%). After adjusting for 15 covariates composed of three sets (demographic characteristics, lifestyles, and health status), digestive diseases were associated with a higher risk of sarcopenia (HR = 1.241, 95% CI = 1.034-1.490, P < 0.05). The associations were more pronounced among men, older adults aged 60-79, rural residents, and married people. In addition, the association between digestive diseases and sarcopenia was robust in the sensitivity analysis. Conclusion: Digestive diseases were associated with an increased risk of sarcopenia in middle-aged and older adults aged ≥45 years. Early intervention of digestive diseases may help to reduce the incidence of sarcopenia in middle-aged and older adults.
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Objective: This study aims to examine the association between childhood traumatic events (CTEs), childhood trauma severity, and depressive symptoms, as well as to examine the mediating and moderating roles of resilience in these associations. Methods: We conducted a cross-sectional study of 1,091 community-dwelling older adults in Jinan, China. The trauma history questionnaire (THQ) was used to measure CTEs and childhood trauma severity. CTEs were defined as the number of traumatic events before the age of 18. We calculated childhood trauma severity by multiplying the number of CTEs by the participants' self-perceived impact level of the events from the THQ. We then applied the 15-item Geriatric Depression Scale and 10-item Connor-Davidson Resilience Scale to assess participants' depressive symptoms and resilience, respectively. Linear regression models were used to examine the associations, and structural equation modeling was used to examine the mediating and moderating roles of resilience. Results: Childhood traumatic events, childhood trauma severity, and resilience were all associated with depressive symptoms in older adults. Resilience mediated the relationship between childhood trauma severity and depressive symptoms (ß = 0.082, 95% CI = 0.045-0.123), accounting for 26.6% of the overall effect (ß = 0.308, 95% CI = 0.190-0.422). However, there was no evidence that resilience mediated the association between CTEs and depressive symptoms. In addition, we did not find that resilience played a moderating role in the associations of CTEs, childhood trauma severity with depressive symptoms. Conclusion: Resilience plays a mediating role in the relationship between childhood trauma severity and depressive symptoms. Intervention measures on improving resilience may reduce childhood trauma severity associated with depression risk in older Chinese adults.
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Experiencias Adversas de la Infancia , Resiliencia Psicológica , Humanos , Anciano , Persona de Mediana Edad , Depresión , Vida Independiente , Estudios Transversales , Pueblos del Este de AsiaRESUMEN
Objective: Digital divide in health-related technology use is a prominent issue for older adults. Improving eHealth literacy may be an important solution to this problem. This study aimed to explore the associations between health literacy, digital skills, and eHealth literacy among older Chinese adults. Methods: A total of 2,144 older adults (mean age, 72.01 ± 6.96 years) from Jinan City, China participated in this study. The eHealth Literacy Scale was used to measure eHealth literacy in older adults. A linear regression model was used to analyze the associations among health literacy, digital skills, and eHealth literacy in older Chinese adults. Results: The mean eHealth literacy score of the older adults was 17.56 ± 9.61. After adjusting for sociodemographic characteristics and experience of Internet usage, the results of the linear regression showed that health literacy (B = 0.258, 95% confidence interval (CI) = 0.215-0.302, P< 0.001) and digital skills (B = 0.654, 95% CI = 0.587-0.720, P < 0.001) were positively associated with eHealth literacy. Sensitivity analyses revealed that this association remained robust. Conclusions: The level of eHealth literacy in older Chinese adults is low. Health literacy and digital skills are associated with eHealth literacy in older adults. In the future, eHealth literacy intervention research should be considered from the perspective of health literacy and digital skills.
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OBJECTIVES: The development and validation of the specific health literacy assessment tool for older adults is the basis for conducting the research on health literacy among older adults. The existing health literacy assessment scale for older adults in Chinese mainland has some limitations, such as too many items and poor compliance during the survey. It is necessary to develop or introduce simplified assessment tools to support large-scale surveys in the future. This study aims to modify the brief health literacy assessment scale compiled by Taiwan scholars, and to conduct the test for the reliability, validity and the measurement equivalence across gender in the older population in mainland China. METHODS: From March to April 2021, 508 older adults from Jinan, Shandong Province, China were selected by cluster sampling method to conduct a questionnaire survey using the brief health literacy assessment scale and health-promoting lifestyle profile. After 4 weeks, 83 of them were selected for retesting. SPSS 25.0 statistical software was used for descriptive analysis, item analysis, exploratory factor analysis, correlation analysis, and reliability test, and Mplus 8.0 was used for confirmatory factor analysis and gender measurement equivalence test. RESULTS: Each item of the scale had good discrimination, and there were significant differences in the scores of each item between high score and low score groups (P<0.05), and the coefficient of correlation between the scores of each item and the total score was between 0.721 and 0.891. Exploratory factor analysis extracted a factor with a characteristic root greater than 1, and the cumulative variance interpretation amount was 67.94%. The confirmatory factor analysis showed that the single factor structure fit was good [χ2/df was 2.260, the Tucker-Lewis index was 0.973, the comparison fit index (CFI) was 0.982, and the root mean square error of approximation (RMSEA) was 0.071]. The multi-group confirmatory factor analysis results showed that the brief health literacy assessment scale's configural equivalence, weak equivalence, and strong equivalence models were all accepted. The comparison results of measurement equivalence models showed that the changes of RMSEA were less than 0.015, and the changes of CFI were less than 0.01, indicating that the brief health literacy assessment scale had measurement equivalence between different gender groups. Cronbach's α coefficient was 0.945, and the test-retest reliability was 0.946. The correlation coefficient between health literacy and health-promotion lifestyles was 0.557 (P<0.05). CONCLUSIONS: The brief health literacy assessment scale has good reliability, validity, and measurement equivalence across gender, and can be used as an effective measurement tool for the health literacy of the older people in Chinese mainland.
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Alfabetización en Salud , Humanos , Anciano , Reproducibilidad de los Resultados , Alfabetización en Salud/métodos , Psicometría , Encuestas y Cuestionarios , Pueblo Asiatico , China , Análisis FactorialRESUMEN
Objective: Lung squamous cell carcinoma (LUSC) is a common respiratory malignancy and presents an increasing prevalence. Ferroptosis is a newly identified controlled cell death that has captured clinical attention worldwide. However, the ferroptosis-related lncRNA expression in LUSC and its relevance to prognosis remain elusive. Methods: The research measured predictive ferroptosis-related lncRNAs in LUSC samples from the TCGA datasets. Data on the stemness indices (mRNAsi) and corresponding clinical characteristics were obtained from TCGA. A prognosis model was established using the LASSO regression. Changes within the neoplasm microenvironment (TME) and medicine association were examined to grasp higher immune cell infiltration in numerous risk teams. In line with coexpression studies, the expression of lncRNAs is closely associated with that of ferroptosis. They were overexpressed in unsound people in the absence of alternative clinical symptoms. Results: The low-risk and speculative teams were considered to have substantial differences in CCR and inflammation-promoting genes. C10orf55, AC016924.1, AL161431.1, LUCAT1, AC104248.1, and MIR3945HG were highly expressed in the high-risk group, suggesting their involvement in the oncology process of LUSC. Moreover, AP006545.2 and AL122125.1 were considerably higher in the low-risk group, implying the potential of these genes as LUSC tumor suppressor genes. The biomarkers listed above may serve as therapeutic targets for LUSC. lncRNAs were also linked to patient outcomes in the LUSC trial. Conclusion: lncRNAs of ferroptosis were overexpressed in the high-risk cohort without other clinical signs, implying their potential to predict BLCA prognosis. GSEA highlighted immunological and tumor-related pathways in the high-risk group. LUSC occurrence and progression are linked to lncRNAs of ferroptosis. Corresponding prognostic models help forecast the prognosis of LUSC patients. lncRNAs of ferroptosis and associated immune cell infiltration in the tumor microenvironment (TME) may serve as potential therapeutic targets in LUSC, which requires further trials. In addition, the lncRNAs of ferroptosis signature offer a viable alternative to predict LUSC, and these ferroptosis-lncRNAs show a prospective research area for LUSC-targeted treatment in the future.
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Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Ferroptosis , Neoplasias Pulmonares , ARN Largo no Codificante , Humanos , Pronóstico , Ferroptosis/genética , Estudios Prospectivos , ARN Largo no Codificante/genética , Microambiente Tumoral/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , PulmónRESUMEN
Background: Fuzheng Nizeng Decoction (FZNZ) has a history of decades in gastric precancerous lesions (GPL) treatment, which has shown clear clinical efficacy. Blocking GPL is a key measure to reduce the incidence of gastric cancer (GC). Therefore, we aim to investigate the mechanism of FZNZ-induced ferroptosis and endoplasmic reticulum (ER) in MNNG-induced gastric precancerous lesion (MC) cells, which has been rarely studied in Traditional Chinese Medicine (TCM). Methods: First, CCK8 and lactate dehydrogenase assays were conducted to study the potential effect of FZNZ on MC cells. Second, combined transcriptomic and metabolomic analysis were used to explore the effect and mechanism of FZNZ. Functionally, the occurrence of ferroptosis was assessed by transmission electron microscopy morphological observation and measurement of ferrous iron levels, lipid peroxidation, and glutathione levels. Finally, the expression levels of mRNAs or proteins related to ferroptosis and ER stress were determined by qPCR or western blot assays, respectively. Results: FZNZ inhibited MC cells viability and induced cell death. By metabolomics coupled with transcriptomics analysis, we found that the mechanism of FZNZ treatment induced ferroptosis and was related to glutathione metabolism and ER stress. We then, for the first time, found that FZNZ induced ferroptosis, which contributed to an increase in intracellular ferrous iron, reactive oxygen species, and malondialdehyde and a decrease in glutathione. Meanwhile, the protein level of glutathione peroxidase 4 (GPX4) was decreased. The mRNA levels of ATF3/CHOP/CHAC1, which are related to ferroptosis and ER stress, were also upregulated. Conclusion: Our results elaborate that FZNZ could induce ferroptosis and ER stress in MC cells, and reduce GPX4/GSH. ATF3/CHOP/CHAC1 may play a crosstalk role, which provides a new molecular mechanism for the treatment of GPL.
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Background: Chronic inflammation is considered one of the main mechanisms leading to frailty. It has been demonstrated that tea consumption reduces chronic inflammation. Few epidemiological studies have investigated the association between tea consumption and frailty. Objective: This study aimed to analyze the association between tea consumption and frailty in Chinese older adults. Methods: Between March and May 2021, we enrolled 2,144 older adults aged ≥60 years in Jinan City, Shandong Province, China, using multi-stage stratified cluster sampling. We assessed tea consumption and frailty in older adults using the Tilburg Frailty Indicator (TFI) and the frequency of tea consumption, respectively. We applied multiple logistic regression analysis to examine the association between tea consumption and frailty, controlling for a set of potential covariates. Results: The prevalence of frailty among older Chinese adults was 38.3% (821/2,144). Tea consumption was categorized as daily (30.4%), occasionally (20.9%), and rarely or never (48.7%). As indicated by the fully adjusted model, daily tea consumption was associated with a lower prevalence of frailty (OR = 0.73, 95%CI = 0.57-0.94). However, this association only applied to men, younger older adults aged 60-79 years, rural residents, and regular participants in community activities. In addition, we observed a linear relationship between tea consumption and the prevalence of frailty (P for trend = 0.017). Conclusions: Higher tea consumption was associated with a lower prevalence of frailty in older adults, especially those men, older adults aged 60-79, rural residents, and individuals who regularly participated in community activities. Further longitudinal and experimental studies are needed to determine the causation between tea consumption and frailty.
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Background: Several studies have shown that neurodegenerative diseases (e.g., Parkinson's disease [PD] and Alzheimer's disease [AD]) are associated with inflammatory bowel disease (IBD), but the causality and direction of their associations remain unclear. Mendelian randomization (MR) studies have explored the causal effects of IBD on PD and AD. However, only a few studies examined this reverse association. Thus, this study aimed to explore whether there are causal associations of genetically predicted PD and AD with IBD, using a two-sample MR study. Methods: Summary statistics for IBD, ulcerative colitis (UC), and Crohn's disease (CD) were derived from a genome-wide association study (GWAS) meta-analysis, which included the International IBD Genetics Consortium and the UK IBD Genetics Consortium (n=59,957). Genetic variants associated with the largest meta-analysis of GWAS of PD (n=1,474,097) and AD (n=455,258) were used as instrumental variables. We used multiple methods, including inverse variance weighted (IVW), weighted median (WM), MR-Egger regression, weighted mode, and Robust Adjusted Profile Score (RAPS) methods, to estimate the effects of genetically predicted PD and AD on IBD. To confirm the validity of the analysis, we also evaluated the pleiotropic effects, heterogeneity, and leave-one-out sensitivity analysis that drive causal associations. Results: The results of the IVW method, WM, and RAPS showed that genetically predicted PD was significantly associated with an increased risk of UC (odds ratio [OR]IVW=1.068, OR WM=1.107, OR RAPS=1.069, all P<0.05). Additionally, we found that there were significant associations of genetically predicted PD with CD (OR IVW=1.064, OR RAPS=1.065, all P<0.05) and IBD (OR IVW=1.062, OR RAPS=1.063, all P<0.05) using the IVW method and RAPS. However, there was no significant causal evidence of genetically predicted AD in IBD, UC, or CD among all MR methods. In all MR analyses, there were no horizontal pleiotropy (all P>0.05), or statistical heterogeneity. The sensitivity analysis results of the leave-one-out sensitivity analysis showed that the causal effect estimations of genetically predicted PD and AD on IBD were robust. Conclusions: Our MR study corroborated a causal association between genetically predicted PD and IBD but did not support a causal effect of genetically predicted AD on IBD. More animal experiments or population-based observational studies are required to clarify the underlying mechanisms of PD and IBD.
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Enfermedad de Alzheimer , Enfermedades Inflamatorias del Intestino , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Enfermedad de Alzheimer/genética , Enfermedad Crónica , Estudio de Asociación del Genoma Completo , Humanos , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/genética , Análisis de la Aleatorización Mendeliana , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/genética , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Objectives: This study aimed to explore the longitudinal associations between eHealth literacy, health-promoting lifestyles, and health-related quality of life (HRQoL) among college students. Methods: From December 2019 (T1) to December 2020 (T2), we administered the eHealth literacy scale, Short-Form Health Survey (SF-12), and Short-Form Health-Promoting Lifestyle Profile Scale to 1,181 college students in Jinan, China. Participants were recruited for 12 months for the two-stage survey. Results: Stable positive correlations were shown between eHealth literacy, health-promoting lifestyles, and HRQoL across time. The cross-lagged analysis showed that eHealth literacy at T1 predicted health-promoting lifestyles at T2 (ß = 0.080, P = 0.006); however, health-promoting lifestyles at T1 did not predict eHealth literacy at T2 (ß = -0.026, P = 0.499). HRQoL at T1 predicted health-promoting lifestyles at T2 (ß = 0.147, P < 0.001); however, similar to the eHealth literacy finding, health-promoting lifestyles at T1 did not predict HRQoL at T2 (ß = 0.045, P = 0.142). eHealth literacy was also bi-directionally associated with HRQoL, and the prediction effect of eHealth literacy at T1 to HRQoL at T2 (ß = 0.078, P = 0.008) was slightly higher than the prediction effect of HRQoL at T1 to eHealth literacy at T2 (ß = 0.074, P = 0.023). Conclusion: eHealth literacy and HRQoL may be antecedents for college students' health-promoting lifestyles. There may be significant bi-directional relationships between eHealth literacy and HRQoL.