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Preeclampsia (PE) is a complication of pregnancy characterized by the new onset of hypertension after 20 weeks of gestation. The incidence of PE is steadily rising, posing a significant threat to the lives of both the pregnant woman and the fetus. Most studies on PE pathogenesis currently focus on the placenta, but maternal decidualization forms the foundation for placental growth and development. Recent studies have shown that impaired decidualization is also a cause of PE. Decidualization is a process where endometrial stromal cells gradually transform into secretory decidual cells during early pregnancy. While NSUN5 encodes a member of a conserved family of proteins, its role in pregnancy remains unknown. In this study, we conducted experiments and observed a significant downregulation of NSUN5 expression in severe preeclampsia decidual tissues compared to those of normal pregnant women. When inducing decidualization in vitro, we found an increase in NSUN5 expression. However, when we used siRNA to knockdown NSUN5 expression, the process of decidualization was prevented. Moreover, we observed a decrease in ATP content during both cell decidualization and after knockdown of NSUN5. Finally, through immunoprecipitation combined with mass spectrometry, we discovered that the protein ATP5B interacts with NSUN5. Furthermore, after knocking down ATP5B using siRNA, we observed impaired decidualization. Moreover, transfection with siRNA to suppress NSUN5 resulted in a decrease in ATP5B expression. These significant findings provide strong evidence that NSUN5 plays a crucial role in decidualization and is closely associated with the development of PE through its interaction with ATP5B.
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BACKGROUND: The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare. CASE PRESENTATION: A 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant 18F-FDG uptake on 18F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis. CONCLUSION: Physicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis.
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Neoplasias Ósseas , Linfocitose , Neoplasias Pleurais , Timoma , Humanos , Feminino , Pessoa de Meia-Idade , Timoma/patologia , Timoma/diagnóstico por imagem , Timoma/complicações , Timoma/diagnóstico , Linfocitose/patologia , Linfocitose/diagnóstico , Neoplasias Pleurais/secundário , Neoplasias Pleurais/patologia , Neoplasias Pleurais/complicações , Neoplasias Pleurais/diagnóstico , Neoplasias Ósseas/secundário , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias do Timo/patologia , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico , Linfócitos T/patologia , Fluordesoxiglucose F18 , Diagnóstico Diferencial , Pleura/patologia , Pleura/diagnóstico por imagemRESUMO
BACKGROUND: Polypharmacy is associated with the prescription of inappropriate medications and avoidable medication-related harm. A novel pharmacist-led intervention aims to identify and resolve inappropriate medication prescriptions in older adults with polypharmacy. AIM: To conduct a preliminary feasibility assessment of the intervention in primary care, testing whether specific components of the intervention procedures and processes can be executed as intended. METHOD: The mixed-methods study was approved by the New Zealand Health and Disability Ethics Committees and public health agency. Patients from a New Zealand general practice clinic were recruited over 4 weeks to receive the intervention. The preliminary feasibility assessment included measures of intervention delivery, patient-reported outcome measures, and perspectives from ten patients and six clinicians. Data were analysed quantitatively and qualitatively to determine if a full-scale intervention trial is warranted. The study's progression criteria were based on established research and guided the decision-making process. RESULTS: The intervention met the study's progression criteria, including patient recruitment, retention, and adherence to the intervention procedures. However, several modifications were identified, including: (1) enhancing patient recruitment, (2) conducting a preliminary meeting between the patient and pharmacist, (3) supporting pharmacists in maintaining a patient-centred approach, (4) reviewing the choice of patient-reported outcome measure, (5) extending the 8-week follow-up period, (6) allocating more time for pharmacists to conduct the intervention. CONCLUSION: The study found the intervention feasible; however, additional development is required before progressing to a full-scale trial. This intervention has the potential to effectively reduce medication-related harm and improve outcomes for older adults with polypharmacy. TRIAL REGISTRATION NUMBER: ACTRN12621000268842 Date registered: 11/03/2021.
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The elasticity matrix and the coefficients of thermal expansion (CTEs) of 8-harness satin-woven (8HS) carbon-fiber-reinforced carbon matrix (C/C) composites at high temperatures were obtained by the asymptotic homogenization method (AHM) and finite element method (FEM). By analyzing the microstructure of the 8HS C/C composites, a representative volume element (RVE) model considering a braided structure was established. The effects of the temperature and component volume fraction on the elasticity matrix and CTEs of the composites were investigated. The sensitivity of model parameters, including the size of RVE model and mesh sensitivity, were studied. The optimal calculation model was employed. In addition, the effects of the 4HS methods and 8HS methods on the elastic constants of the composites were compared. The temperature and variation in the carbon fiber volume fraction were found to have a significant impact on the elasticity matrix and CTEs of composite materials. At the same volume fraction of carbon fibers, some elastic coefficients of the 4HS composite material were slightly lower than those of 8HS composite material. This research affords a computational strategy for the accurate prediction of the themo-mechanical properties of satin-woven C/C composites.
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Appropriate nitrogen (N) management system is essential for effective crop productivity and minimizing agricultural pollution. However, the underlying mechanistic understanding of how N fertilizer regulates crop yield via soil properties in soils with different fertilities remains unresolved. Here, we used a field experiment that spanned 3 cropping seasons to evaluate the grain yield (GY), aboveground biomass and N recovery efficiency (NRE) after treatment with five N fertilizer application rates (N0, N75, N112, N150, and N187) in soils with three levels of fertility. Our results indicated that the highest GY across low, moderate, and high fertility soils were 1.5 t hm-2 (N150), 4.9 t hm-2 (N187), and 5.4 t hm-2 (N112), respectively. The highest aboveground biomass and NRE were observed at N150 for all three levels of soil fertility, while only the N uptake by aboveground biomass of low and high fertility soils decreased at N187, confirming that excessive N fertilization results in a further decline in crop N uptake. The relationship between GY, NRE and N fertilizer application rates fit the unary quadratic polynomial model. To achieve a balance between grain production and environmental benefits in N fertilizer, appropriate N fertilizer rates were determined to be 97.5 kg hm-2, 140 kg hm-2 and 131 kg hm-2 for low, moderate and high fertility soils, respectively. Structural equation modeling suggested that GY was significant correlated with soil microbial biomass carbon (SMBC) and N directly in low fertility field, with SMBC directly in moderate fertility field, and via SOC and NO3 -N in high fertility field. Therefore, a soil-based management strategy for N fertilizers could enhance food security while reducing agricultural N fertilizer inputs to mitigate environmental impacts.
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BACKGROUND: Tumor-derived exosomal miRNAs play crucial roles in cancer diagnosis. Current studies aim to identify exosomal miRNAs associated with colorectal cancer (CRC) that are noninvasive, sensitive, and specific. PATIENTS AND METHODS: Exosomes were extracted from CRC patients and healthy donors via ultracentrifugation, followed by verification via transmission electron microscopy (TEM), qNano, and Western blot analysis. The differential expression levels and clinical characteristics of miR-205-5p were analyzed in CRC via data from The Cancer Genome Atlas (TCGA). Real-time quantitative PCR was used to assess the expression levels of exosomal miRNAs in 157 primary CRC patients, 20 patients with benign diseases, and 135 healthy donors. Predictions regarding target genes were made to guide further exploration of the disease's etiopathogenesis through bioinformatics. RESULTS: Compared with that in healthy donors, the expression of miR-205-5p in colorectal cancer (CRC) patients was significantly lower, as determined through analysis of the TCGA database. We conducted a prediction and analysis of the functional enrichment of downstream target genes regulated by miR-205-5p. A lower level of exosomal miR-205-5p in the serum of CRC patients than in that of healthy controls (p < 0.0001) and patients with benign disease (p < 0.0001) was observed. Furthermore, the expression levels of exosomal miR-205-5p were significantly lower in early-stage CRC patients than in the comparison groups (p<0.001 and p < 0.0001). Notably, the expression levels of exosomal miR-205-5p significantly increased postoperatively (p = 0.0053). CONCLUSIONS: The present study demonstrated that serum exosomal miR-205-5p may be a diagnostic biomarker for CRC.
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BACKGROUND: Despite increased literature focusing on the role of the built environment (BE) in health, few cohort studies have quantitatively analyzed neighborhood walkability environment in relation to the risk of death and cardiovascular disease (CVD). This longitudinal study aimed at evaluating the association between perceived BE attributeswith mortality and major CVD based on the Prospective Urban Rural Epidemiology study in China (PURE-China). METHODS: The PURE-China study recruited 47,931 participants aged 35-70 years from 12 provinces of China between 2005 and 2009. The perceived BE information, including land use, street, aesthetics, and safety, was collected using the neighborhood environment walkability scale (NEWS) questionnaire, with higher scores indicating a more favorable rating. Two primary outcomes are all-cause mortality and major CVD event. The Cox frailty model with random intercepts was used to assess the association between the perceived total BE/subscales score and outcomes. RESULTS: Of 32,163 participants included in this study, 19,253 (59.9 %) were women, and the mean (SD) age was 51.0 (9.5) years. After a median follow-up period of 11.7 years (IQR 9.4 - 12.2), we observed that one standard deviation higher of combined BE scores was related to a lower risk of all-cause mortality (HR = 0.85; 95 %CI, 0.80-0.90), and major CVD events (HR = 0.95; 95 %CI, 0.90-0.99). The subscales of perceived BE were related to a lower risk, although a few were not significant. Land use mix-diversity and safety from crime were the two most significant subscales. Stronger risks were observed among urban and female participants. CONCLUSION: Favorable perceived BE characteristics were linked with a lower risk of all-cause mortality and major CVD events in Chinese population, especially in urban areas and females. Our findings can be used by policymakers to take action to mitigate the adverse effect of poor community conditions on health, such as improving local amenities and transport connectivity, providing building paths for walking, running and cycling.
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Ambiente Construído , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , Pessoa de Meia-Idade , Feminino , China/epidemiologia , Masculino , Adulto , Estudos Prospectivos , Idoso , Ambiente Construído/estatística & dados numéricos , Inquéritos e Questionários , População Rural/estatística & dados numéricos , Estudos Longitudinais , Características de Residência/estatística & dados numéricos , CaminhadaRESUMO
Background: Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. Methods: The INTERSTROKE study is a case-control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). Findings: Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46-1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61-2.11) than ICH (OR 1.19 95% CI 1.00-1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24-4.10) and PAR (18.6%, 15.1-22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63-2.87) and undetermined cause (OR 1.97, 95% CI 1.55-2.50). Both filtered (OR 1.73, 95% CI 1.50-1.99) and non-filtered (OR 2.59, 95% CI 1.79-3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69-2.27), ischemic stroke (OR 1.89, 95% CI 1.59-2.24) and ICH (OR 2.00, 95% CI 1.60-2.50). Interpretation: There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. Funding: The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.