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INTRODUCTION: Preoperative inspiratory muscle training (IMT) is recognised as an important component of the preoperative management of lung cancer, although there is limited evidence for the delivery of a home-based IMT programme combined with preoperative education. We developed a programme combining short-term home-based IMT and preoperative physiotherapy education ('the programme'). This study aims to evaluate the effectiveness of this programme in reducing postoperative pulmonary complications (PPCs) after lung cancer resection compared with standard care. METHODS AND ANALYSIS: In this randomised controlled trial, 114 participants scheduled for lung cancer surgery at the First Affiliated Hospital of Fujian Medical University will be randomly assigned (1:1) to either receive usual care (information booklet) or usual care combined with the programme, which consist of short-term home-based IMT and preoperative physiotherapy education. The primary outcome measure will be PPCs using the Melbourne Group Score. Secondary outcomes will include health-related quality of life, maximal inspiratory pressure, 6 min walk distance, length of hospital stay, anxiety and depression levels, and hospital costs. ETHICS AND DISSEMINATION: The study has received ethics approval from the ethics committee of the first affiliated hospital of Fujian Medical University (approval no: MRCTA, ECFAH of MFU [2021]569). Participants will be required to provide written informed consent. The results of the study will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2300067464.
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Exercícios Respiratórios , Neoplasias Pulmonares , Complicações Pós-Operatórias , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Neoplasias Pulmonares/cirurgia , Exercícios Respiratórios/métodos , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/métodos , Qualidade de Vida , Educação de Pacientes como Assunto/métodos , Músculos Respiratórios/fisiopatologia , Exercício Pré-OperatórioRESUMO
BACKGROUND: Patients with cleft lip and palate anomalies suffer from associated negative psychosocial effects despite undergoing reconstructive surgeries. Discrimination from others may be a contributing factor. We aim to understand whether people react differently to cleft and non-cleft subjects in questions regarding aesthetic appraisal and interpersonal impressions, as well as whether diverging opinions exist between people of different backgrounds. MATERIALS AND METHODS: Using the 3dMD system, three-dimensional craniofacial images of cleft (n = 20) and non-cleft (n = 5) pediatric individuals were obtained and used to create a Likert scale-based questionnaire. Participants from three different backgrounds, including adolescent peers, adult laypersons, and plastic surgeons, were recruited to complete the assessment. The resulting data were transferred to a bar graph and analyzed with the item response theory-graded response model to estimate the latent traits and capability of each subject. RESULTS: Non-cleft images obtained more positive responses than cleft images in questions of both aesthetic appraisal and interpersonal impressions. However, some of the cleft images were rated similarly, or even superior, to non-cleft images in questions regarding interpersonal impressions. Surgeons showed the greatest latent capability in differentiating between cleft and non-cleft images, followed by adult laypersons, and then adolescent peers. CONCLUSIONS: Despite cleft patients experiencing drastic improvements in appearance post-repair, all subject groups responded differently to questions concerning aesthetic and social impressions of pediatric cleft and non-cleft images. Plastic surgeons were more critical than others. These findings may offer further insight to clinicians, educators, and caregivers into the social challenges faced by cleft individuals.
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OBJECTIVES: This study seeks to investigate the potential correlation between various levels of frailty and suicidal ideation (SI) in older adults from the USA. METHODS: Our cross-sectional study extracted data on adults ≥60 years from the NHANES in 2005-2018. Frailty levels were assessed by computing the Frailty Index, classifying individuals into robust, prefrail, and frail categories. SI was evaluated utilizing Item #9 of PHQ-9. Logistic regression and restricted cubic splines were employed for analysis. RESULTS: The analysis comprised 8564 participants, revealing that 3.3% reported experiencing SI. The association between frailty and SI in older adults was statistically significant in crude model (OR: 5.94, 95% CI: 3.46-11.27, P < 0.001). Upon adjusting for baseline characteristics, the association remained robust (AOR: 5.35, 95% CI: 3.09-10.19, P < 0.001). Model II did not substantially alter the association between frailty and SI after further adjustment for lifestyle factors (AOR: 5.23, 95% CI: 3.02-9.98, P < 0.001). In a sensitivity analysis controlling for depression, the association remained statistically significant (AOR:3.62, 95%CI: 1.76-8.75, P = 0.001). Furthermore, the associations between the Frailty Index and SI were pronounced in the restricted cubic spline (RCS) models (P overall < 0.001, P nonlinearity = 0.771). CONCLUSION: Frailty appears to heighten vulnerability to suicidal ideation in older adults. Training healthcare professionals to identify and address mental health issues related to frailty is crucial. Through comprehensive intervention measures, we can better safeguard the mental well-being of older adults and reduce the risk of suicide.
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AIMS: Population aging is a challenge that the whole world is facing, especially in China. This study aims to investigate the current distribution status of nursing homes in China using spatial epidemiology methods. DESIGN: Cross-sectional study in China. METHODS: The data were obtained from the Integrated Civil Affairs Government Service Platform 'China County Statistical Yearbook' for 2020 and the 'China City Statistical Yearbook' for 2020. Using global Moran's index to test the clustering of nursing homes, inter-group and intra-group Theil index was utilised to differentiate the sources of differences. The coupling coordination analysis was conducted to explore the coordination. Geographically weighted regression was utilised to investigate the impact of economic development and aging on nursing home resources. All analyses were conducted by Arcgis 10.8 and R Studio 4.3.2. RESULTS: Global Moran's index indicated that the distribution of nursing homes in China exhibited clustering. The Theil index values for institutions and beds at the national county were 0.32450 and 0.30675. However, upon comparing provinces and regions, it was found that the differences across the country mainly stem from within provinces (contribution rate: institutions 65.0%; beds 73.0%) and within regions (contribution rate: institutions 99.0%; beds 91.0%). The majority of districts and counties had a coupling coordination index of institutions and bed numbers, both of which were < 0.5. CONCLUSION: The development of nursing home resources in China has been rapid, generally presenting a balanced state, but further optimisation is needed. This study established a foundation for the targeted distribution of essential public services, focusing on nursing home healthcare resources tailored to the needs of older persons. IMPLICATIONS: The study underscored the urgent need for targeted elderly care policies, emphasising the optimisation of resource distribution to enhance the overall quality of care provided to the aging population. NO PATIENTS OR PUBLIC CONTRIBUTION: The study did not involve humans.
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Background: The treatment-free interval is a significant predictor of worse prognosis and poor response rates of the second-line treatment in patients with carboplatin and paclitaxel (PT)-pretreated, advanced, or recurrent endometrial cancer (EC). Whether lenvatinib plus pembrolizumab still confers a survival benefit compared with doxorubicin in patients with platinum-free intervals of <6 months remains unclear. Methods: This multi-institutional retrospective analysis was performed using de-identified electronic health records from the TriNetX Research Network. Patients with advanced or recurrent ECs who received lenvatinib plus pembrolizumab or doxorubicin within six months of first-line PT were identified. A 1:1 propensity score matching (PSM) was conducted to control for potential confounding variables. Overall survival (OS) and adverse event profile were the primary and secondary outcomes. Results: Between January 2018 and February 2024, 130 patients with PT-treated, advanced, or recurrent ECs who received lenvatinib plus pembrolizumab and 122 patients who received doxorubicin at a platinum-free interval of <6 months were identified across 31 healthcare organizations. In the balanced cohort following PSM with 117 patients in each group, treatment with lenvatinib plus pembrolizumab was associated with improved OS compared with treatment with doxorubicin (12.8 vs. 8.2 months, p = 0.012, hazard ratio: 0.65, 95% confidence interval: 0.46-0.91). Regarding adverse event analysis, a higher incidence of hypothyroidism and proteinuria was observed with lenvatinib plus pembrolizumab, and more hematological toxicities were observed with doxorubicin. Conclusions: in patients with treatment-free intervals of <6 months, lenvatinib plus pembrolizumab still confers improved survival compared with doxorubicin in PT-treated, advanced, or recurrent ECs.
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Structural color, a color generated based on physical principles, has broad applications such as displays, optical sensors, and anti-counterfeiting. Traditional methods for producing structural colors are often complex and time-consuming, whereas spray-coating colloidal self-assembly offers a simple and controllable alternative. However, due to the high-pressure atomization process, colloidal inks often form amorphous photonic structures (APSs), making it challenging to precisely control the assembly of colloidal particles on substrates to achieve ordered structures. By rationally designing the composition of colloidal mixed solutions, controlling particle concentration, and adjusting evaporation temperatures, it is possible to effectively regulate the assembly of colloidal particles and obtain angle-dependent iridescent colors. This work proposes a simple spray-coating process that enables the control of both ordered and disordered structures, with tunable optical properties, suitable for colloidal patterning on various substrates. This method not only simplifies the fabrication of photonic crystals (PCs) but also has broad potential, particularly in anti-counterfeiting, where it enables the creation of hard-to-replicate structured patterns with enhanced security.
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Frozen shoulder (FS) is a common shoulder condition accompanied by shoulder pain and a loss of shoulder range of motion (ROM). The typical clinical assessment tools such as questionnaires and ROM measurement are susceptible to subjectivity and individual bias. To provide an objective evaluation for clinical assessment, this study proposes an inertial measurement unit (IMU)-based identification system to automatically identify shoulder tasks whether performed by healthy subjects or FS patients. Two groups of features (time-domain statistical features and kinematic features), seven machine learning (ML) techniques, and two deep learning (DL) models are applied in the proposed identification system. For the experiments, 24 FS patients and 20 healthy subjects were recruited to perform five daily shoulder tasks with two IMUs attached to the arm and the wrist. The results demonstrate that the proposed system using deep learning presented the best identification performance using all features. The convolutional neural network achieved the best identification accuracy of 88.26%, and the multilayer perceptron obtained the best F1 score of 89.23%. Further analysis revealed that the identification performance based on wrist features had a higher accuracy compared to that based on arm features. The system's performance using time-domain statistical features has better discriminability in terms of identifying FS compared to using kinematic features. We demonstrate that the implementation of the IMU-based identification system using ML is feasible for FS assessment in clinical practice.
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Bursite , Aprendizado de Máquina , Amplitude de Movimento Articular , Ombro , Humanos , Masculino , Feminino , Amplitude de Movimento Articular/fisiologia , Bursite/fisiopatologia , Bursite/diagnóstico , Pessoa de Meia-Idade , Fenômenos Biomecânicos/fisiologia , Ombro/fisiologia , Adulto , Aprendizado Profundo , Redes Neurais de Computação , IdosoRESUMO
With the advancement of Artificial Intelligence (AI), it has had a profound impact on medical education. Understanding the advantages and issues of AI in medical education, providing guidance for educators, and overcoming challenges in the implementation process is particularly important.The objective of this study is to explore the current state of AI applications in medical education.A systematic search was conducted across databases such as PsycINFO, CINAHL, Scopus, PubMed, and Web of Science to identify relevant studies. The Critical Appraisal Skills Programme (CASP) was employed for the quality assessment of these studies, followed by thematic synthesis to analyze the themes from the included research.Ultimately, 21 studies were identified, establishing four themes: (1) Shaping the Future: Current Trends in AI within Medical Education; (2) Advancing Medical Instruction: The Transformative Power of AI; (3) Navigating the Ethical Landscape of AI in Medical Education; (4) Fostering Synergy: Integrating Artificial Intelligence in Medical Curriculum.Artificial intelligence's role in medical education, while not yet extensive, is impactful and promising. Despite challenges, including ethical concerns over privacy, responsibility, and humanistic care, future efforts should focus on integrating AI through targeted courses to improve educational quality.
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Leaves evolve shape diversity ranging from simple leaves with smooth margin to complicated shape with toothed/serrated, lobed and dissected leaves with leaflets. In the model plant Arabidopsis thaliana with simple leaves producing serrated margin, boundary regulatory factors CUP SHAPED COTYLEDON 2 (CUC2) and CUC3 play important roles in promoting leaf serration initiation and maintenance. Stem cell related WUSCHEL-RELATED HOMEOBOX1 (WOX1) and PRESSED FLOWER/WOX3 are also essential for leaf margin morphogenesis, but the role of WOX1 and PRS as well as the relationships between CUCs and WOXs on tooth development was unclear. In this study, we found that WOX1, but not PRS, prevents overproduction of tooth number and excessive tooth size by limiting CUC3 expression to a moderate level in a temporally regulated manner. We also revealed that BRASSINAZOLE RESISTANT 1 (BZR1), a known regulator for plant development including boundary regions, is involved in WOX1 negative regulation of tooth development by repressing CUC3 expression during the initiation/early stage of tooth development. WOX1 parallelly limits BZR1 and CUC3 expression from the late stage of the first 2 teeth, while restricts CUC3 activity in a BZR1 dependent manner from the initiation/early stage of subsequently developed teeth. This study uncovers a new mechanism for WOX1 in fine-tuning the leaf margin geometry.
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OBJECTIVE: To explore the differences in ultra-processed food (UPF) consumption across different socioeconomic status (SES) levels. METHODS: Data on UPF consumption (grams/day) were derived from the 2017-2018 National Health and Nutrition Examination Survey. The analysis controlled for age, marital status, race, and sex. A restricted cubic spline (RCS) model was applied to examine the nonlinear response curve. RESULTS: UPF consumption increased with higher poverty income ratio (PIR), the ratio of household income to the established poverty line. Compared to the low PIR group, the medium group showed a non-significant increase (ß = 34.23[95%CI: -28.81, 97.28], p = 0.287), while the high group exhibited a significant increase (ß = 115.15[95%CI: 43.53, 186.76], p = 0.002). A linear positive correlation was observed in RCS analysis (p-nonlinear = 0.166, p-overall < 0.001). CONCLUSIONS: The study highlights that higher SES is associated with greater consumption of UPF in the US. The findings suggest that policy interventions should take SES into consideration.
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In semiconducting monolayer transition metal dichalcogenides (ML-TMDs), broken inversion symmetry and strong spin-orbit coupling result in spin-valley lock-in effects so that the valley degeneracy may be lifted by external magnetic fields, potentially leading to real-space structural transformation. Here, magnetic field (B)-induced giant electric hysteretic responses to back-gate voltages are reported in ML-MoS2 field-effect transistors (FETs) on SiO2/Si at temperatures < 20 K. The observed hysteresis increases with |B| up to 12 T and is tunable by varying the temperature. Raman spectroscopic and scanning tunneling microscopic studies reveal significant lattice expansion with increasing |B| at 4.2 K, and this lattice expansion becomes asymmetric in ML-MoS2 FETs on rigid SiO2/Si substrates, leading to out-of-plane mirror symmetry breaking and the emergence of a tunable out-of-plane ferroelectric-like polar order. This broken symmetry-induced polarization in ML-MoS2 shows typical ferroelectric butterfly hysteresis in piezo-response force microscopy, adding ML-MoS2 to the single-layer material family that exhibits out-of-plane polar order-induced ferroelectricity, which is promising for such technological applications as cryo-temperature ultracompact non-volatile memories, memtransistors, and ultrasensitive magnetic field sensors. Moreover, the polar effect induced by asymmetric lattice expansion may be further generalized to other ML-TMDs and achieved by nanoscale strain engineering of the substrate without magnetic fields.
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BACKGROUND AND PURPOSE: Elevated serum lipoprotein(a) (Lp[a]) levels have been linked to an increased incidence of stroke. This systematic review and meta-analysis aimed to evaluate the impact of serum Lp(a) on the functional outcomes of patients with ischemic stroke (IS). METHODS: We conducted a comprehensive search of the MEDLINE, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure databases to identify relevant cohort studies. A random effects model was utilized to synthesize the data, accounting for study heterogeneity. RESULTS: The analysis included 11 cohort studies comprising 11,958 patients with IS. Pooled results indicated that high baseline Lp(a) levels were associated with an increased risk of poor functional outcomes during follow-up (odds ratio [OR] = 2.13, 95% confidence interval = 1.67-2.71, p < 0.001, I2 = 62%). Subgroup analyses revealed that the relationship between high Lp(a) levels and the risk of poor functional outcomes was more pronounced at discharge (OR = 3.25), 3 months (OR = 2.02), and 6 months (OR = 2.11) poststroke, compared to 12 months (OR = 1.25, p for subgroup difference < 0.001). Furthermore, the association was attenuated yet remained significant in studies adjusting for low-density lipoprotein cholesterol (LDL-C) compared to those that did not adjust for LDL-C (OR = 1.69 vs. 2.63, p for subgroup difference = 0.03). CONCLUSIONS: High serum Lp(a) levels at baseline are significantly associated with poor functional outcomes in patients with IS.
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The myotendinous junction (MTJ) facilitates force transmission between muscle and tendon to produce joint movement. The complex microarchitecture and regional mechanical heterogeneity of the myotendinous junction pose major challenges in creating this interface in vitro. Engineering this junction in vitro is challenging due to substantial fabrication difficulties in creating scaffolds with intricate microarchitecture and stiffness heterogeneity to mimic the native muscle-tendon interface. To address the current challenges in creating the MTJ in vitro, digital light processing (DLP)-based 3D printing was used to fabricate poly(glycerol sebacate)acrylate (PGSA)-based muscle-tendon scaffolds with physiologically informed microstructure and mechanical properties. Local mechanical properties in various regions of the scaffold were tuned by adjusting the exposure time and light intensity used during the continuous DLP-based 3D printing process to match the mechanical properties present in distinct regions of native muscle-tendon tissue using printing parameters defined by an artificial intelligence-trained algorithm. To evaluate how the presence of zonal stiffness regions can affect the phenotype of a 3D-printed MTJ in vitro model, three 3D-printed PGSA-based scaffold conditions were investigated: (1) a scaffold with muscle-informed mechanical properties in its entirety without zonal stiffness regions, (2) a scaffold with one end possessing native muscle stiffness and the other end possessing native tendon stiffness, and (3) a scaffold with three distinct regions whose stiffness values correspond to those of muscle on one end of the scaffold, MTJ in the middle junction of the scaffold, and tendon on the other end of the scaffold. The scaffold containing regional mechanical heterogeneity most similar to the native MTJ (condition 3) was found to enhance the expression of MTJ-related markers compared to those without the presence of zonal stiffness regions. Overall, the DLP-based 3D printing platform and biomaterial system developed in this study could serve as a useful tool for mimicking the complexity of the native MTJ, which possesses inherent geometric and mechanical heterogeneity.
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BACKGROUND: To examine the associations of physical activity (PA) and sedentary behavior (SB) with longevity and age acceleration (AA) using observational and Mendelian randomization (MR) studies, and quantify the mediating effects of lipids. METHODS: In Guangzhou Biobank Cohort Study (GBCS), PA and SB were assessed by the Chinese Version of the International Physical Activity Questionnaire. Longevity was defined as participants whose age at follow-up or at death was at or above the 90th age percentile. AA was defined as the residual resulting from a linear model that regressed phenotypic age against chronological age. Linear regression and Poisson regression with robust error variance were used to assess the associations of total and specific PA in different intensities, and SB with AA and longevity, yielding ßs or relative risks (RRs) and 95% confidence intervals (CIs). Two-sample MR was conducted to examine the causal effects. Mediation analysis was used to assess the mediating effects of lipids. RESULTS: Of 20,924 participants aged 50 + years in GBCS, during an average follow-up of 15.0 years, compared with low PA, moderate and high PA were associated with higher likelihood of longevity (RR (95% CI): 1.56 (1.16, 2.11), 1.66 (1.24, 2.21), respectively), and also cross-sectionally associated with lower AA (ß (95% CI): -1.43 (-2.41, -0.45), -2.09 (-3.06, -1.11) years, respectively). Higher levels of moderate PA (MPA) were associated with higher likelihood of longevity and lower AA, whereas vigorous PA (VPA) showed opposite effects. The association of PA with longevity observed in GBCS was mediated by low-density lipoprotein cholesterol (LDL-C) by 8.23% (95% CI: 3.58-39.61%), while the association with AA was mediated through LDL-C, triglycerides and total cholesterol by 5.13% (3.94-7.30%), 7.81% (5.98-11.17%), and 3.37% (2.59-4.80%), respectively. Additionally, in two-sample MR, SB was positively associated with AA (ß (95% CI): 1.02 (0.67, 1.36) years). CONCLUSIONS: PA showed protective effects on longevity and AA, with the effects being partly mediated through lipids. Conversely, SB had a detrimental impact on AA. MPA was associated with higher likelihood of longevity and reduced AA, whereas VPA showed adverse effects. Our findings reinforce the recommendation of "sit less and move more" to promote healthy longevity, and highlight the potential risks associated with VPA in the elderly.
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Metal-organic frameworks (MOFs) are promising materials for sample pretreatment. The performance improvement of powdered MOFs is hindered by their aggregation and difficult recovery. To overcome these issues, a biodegradable lightweight spherical aerogel was used as a support for the in situ growth of copper-based MOFs (MOF-199). Furthermore, Fe3O4 nanoparticles were incorporated into the aerogel to achieve magnetic properties. Thus, hybrid aerogel spheres containing MOF-199 supported on magnetic oxidized cellulose nanofiber/carboxymethyl chitosan (MOF-199@mag-CNF/CMC) were fabricated. The effects of Fe3O4 loading amount and organic-ligand concentration on the properties (spherical geometry and mechanical strength) of the hybrid aerogel spheres were studied. Their potential application in the extraction of benzodiazepines (BZPs) from urine samples prior to liquid chromatography-mass spectrometry was evaluated. The highly dispersed MOF-199 crystals on the spherical aerogel effectively overcame the inherent structural shrinkage of the bare aerogel spheres; thus, the MOF-199@mag-CNF/CMC aerogel spheres were robust and could withstand repeated use for at least eight consecutive extraction cycles. Further, MOF-199@mag-CNF/CMC exhibited improved BZP extraction efficiency, which was 2.5-11.6 times higher than that of bare Cu2+@mag-CNF/CMC aerogel spheres, primarily due to additional π-π interaction and H-bonding as well as improved specific surface area. Parameters influencing the extraction and desorption processes were also comprehensively investigated. Under optimal conditions, this method provided a wide linear range of 0.1-10 µg/L (R2 > 0.995) and good precision (2.8-6.7% for intra-day; 1.9-7.8 % for inter-day). The limits of detection and quantification ranged from 0.02 to 0.11 µg/L and from 0.06 to 0.33 µg/L, respectively. The recoveries for the urine samples spiked with three concentrations of BZPs ranged from 73.9 % to 114.1 %. The proposed method is simple, sensitive and eco-friendly and can be used for the determination of BZPs from urine for clinical and forensic examinations.
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Benzodiazepinas , Celulose , Quitosana , Estruturas Metalorgânicas , Extração em Fase Sólida , Extração em Fase Sólida/métodos , Estruturas Metalorgânicas/química , Celulose/química , Celulose/análogos & derivados , Quitosana/química , Benzodiazepinas/urina , Benzodiazepinas/química , Benzodiazepinas/isolamento & purificação , Humanos , Limite de Detecção , Géis/química , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Many patients with obesity in Taiwan seek Chinese herbal medicines (CHM) from traditional Chinese medicine (TCM) clinics. This study aimed to estimate the risk of major adverse cardiovascular events (MACEs) in adults diagnosed with obesity, with or without CHM. METHODS: Patients with obesity aged 18 to 50 years were identified using diagnostic codes from Taiwan's National Health Insurance Research Database between 2008 and 2018. We randomized 67,655 patients with or without CHM using propensity score matching. All patients were followed up from the start of the study until MACEs, death, or the end of 2018. A Cox proportional regression model was used to evaluate the hazard ratios of MACEs in the CHM and non-CHM cohorts. RESULTS: During a median follow-up of 4.2 years, the CHM group had a higher incidence of MACEs than the non-CHM control cohort (9.35 versus 8.27 per 1,000 person-years). The CHM group had a 1.13-fold higher risk of MACEs compared with the non-CHM control (adjusted hazard ratio [aHR] = 1.13; 95% confidence interval [CI]: 1.07-1.19; p <0.001), especially in ischemic stroke (aHR = 1.18; 95% CI: 1.07-1.31; p <0.01), arrhythmia (aHR = 1.26; 95% CI: 1.14-1.38; p <0.001), and young adults aged 18 to 29 years (aHR = 1.22; 95% CI: 1.05-1.43; p <0.001). CONCLUSION: Although certain CHMs offer cardiovascular benefits, young and middle-aged obese adults receiving CHM exhibit a higher risk of MACEs than those not receiving CHM. Therefore, TCM practitioners should be cautious when prescribing medications to young patients with obesity, considering their potential cardiovascular risks.
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Histidine kinases (HKs) are important sensor proteins in fungi and play an essential role in environmental adaptation. However, the mechanisms by which fungi sense and respond to fungivores attack via HKs are not fully understood. In this study, we utilized Neurospora crassa to investigate the involvement of HKs in responding to fungivores attack. We found that the 11 HKs in N. crassa not only affected the growth and development, but also led to fluctuations in antioxidant production. Ten mutants in the genes encoding HKs (except ∆phy1) showed increased production of reactive oxygen species (ROS), especially upon Sinella curviseta attack. The ROS burst triggered changes in conidia and perithecial beaks formation, as well as accumulation of ß-glucan, ergothioneine, ergosterol, and carotenoids. ß-glucan was increased in ∆hk9, ∆os1, ∆hcp1, ∆nik2, ∆sln1, ∆phy1 and ∆phy2 mutants compared to the wild-type strain. In parallel, ergothioneine accumulation was improved in ∆phy1 and ∆hk16 mutants and further increased upon attack, except in ∆os1 and ∆hk16 mutants. Additionally, fungivores attack stimulated ergosterol and dehydroergosterol production in ∆hk9 and ∆os1 mutants. Furthermore, deletion of these genes altered carotenoid accumulation, with wild-type strain, ∆hk9, ∆os1, ∆hcp1, ∆sln1, ∆phy2, and ∆dcc1mutants showing an increase in carotenoids upon attack. Taken together, HKs are involved in regulating the production of conidia and antioxidants. Thus, HKs may act as sensors of fungivores attack and effectively improve the adaptive capacity of fungi to environmental stimuli.
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Histidina Quinase , Neurospora crassa , Espécies Reativas de Oxigênio , Neurospora crassa/genética , Neurospora crassa/metabolismo , Histidina Quinase/genética , Histidina Quinase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Esporos Fúngicos/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Animais , Regulação Fúngica da Expressão Gênica , Artrópodes/genética , Artrópodes/microbiologia , Mutação , Adaptação Fisiológica/genética , Ergosterol/metabolismo , beta-Glucanas/metabolismo , Antioxidantes/metabolismo , Carotenoides/metabolismo , ErgotioneínaRESUMO
Responsive photonic crystals (RPCs) presenting tunable structural colors under external stimuli are widely applied in the fields of dynamic displays, sensors, and anticounterfeiting. However, the development of multiresponsive photonic crystal (MRPC) films possessing versatile variable optical properties remains a significant challenge due to the tedious synthetic procedure of multifunctional building blocks and complex assembly processes, thereby constraining their extensive applications. In the present work, a series of soft nanospheres with a hydrophobic cores and responsive hydrophilic shells have been synthesized by a facile one-step surfactant-free emulsion polymerization method. The MRPC patterns were then prepared by depositing soft nanosphere emulsions onto the 3D-printed substrates with a topological structure followed by drying at room temperature. The shells of soft nanospheres deformed and fused with each other, resulting in the formation of transparent MRPC film patterns. The MRPC patterns exhibited brilliant structural color in a wet state but lost the color again after complete drying. Such a reversible structural color was ascribed to the change of the refractive index (RI) of the hydrophilic shell layers of nanospheres according to wetting/drying state shifting. Moreover, the on-demand designed MRPC patterns could rapidly respond to external stimuli of temperature, pH, and organic solvents in a reversible manner, and multichannel encrypted security labels were also demonstrated. We postulate that our facile and feasible approach can be applied to the systematic design and large-scale production of MRPC patterns for a variety of applications.
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Androgen dependence is a key feature of prostate cancer, and androgen deprivation is effective in treating prostate cancer. However, the disease often worsens and develops into castration-resistant prostate cancer after short-term control. The current study aimed to explore the mechanism of the synergistic action of 18ß-glycyrrhetinic acid (18ß-GA) and enzalutamide (ENZ) against prostate cancer. Our findings showed that 18ß-GA significantly inhibited the expression of OATP2B1 and the transport of dehydroepiandrosterone sulfate (DHEAS) in LNCap and 22RV1 cells. It also downregulated the expression of androgen receptor (AR) to some extent. ENZ strongly inhibited AR expression, but it did not affect OATP2B1-mediated uptake of DHEAS. Compared to the effects of 18ß-GA and ENZ alone, the combination of 18ß-GA and ENZ significantly enhanced the inhibitory effects on AR, prostate-specific antigen (PSA) expression, tumor cell proliferation, and migration. The results obtained in castrated model mice matched the findings of in vitro experiments. 18ß-GA significantly reduced the uptake of DHEAS mediated by OATP2B1 in mouse tumor tissues and cooperated with ENZ to further inhibit the expression of AR and PSA, combat the growth of tumor cells, and promote the apoptosis of tumor cells. In conclusion, 18ß-GA considerably decreased the uptake of DHEAS and androgen production in cells by inhibiting the transport function of OATP2B1, while ENZ inhibited the nuclear translocation of AR and reduced the expression of AR. The combination of 18ß-GA and ENZ can simultaneously inhibit androgen production and AR expression and exhibit a synergistic effect against castration and prostate cancer progression.
Assuntos
Benzamidas , Proliferação de Células , Sulfato de Desidroepiandrosterona , Sinergismo Farmacológico , Ácido Glicirretínico , Nitrilas , Transportadores de Ânions Orgânicos , Feniltioidantoína , Neoplasias de Próstata Resistentes à Castração , Receptores Androgênicos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Feniltioidantoína/farmacologia , Feniltioidantoína/análogos & derivados , Feniltioidantoína/uso terapêutico , Humanos , Sulfato de Desidroepiandrosterona/metabolismo , Sulfato de Desidroepiandrosterona/farmacologia , Benzamidas/farmacologia , Linhagem Celular Tumoral , Animais , Nitrilas/farmacologia , Transportadores de Ânions Orgânicos/metabolismo , Ácido Glicirretínico/farmacologia , Ácido Glicirretínico/análogos & derivados , Receptores Androgênicos/metabolismo , Proliferação de Células/efeitos dos fármacos , Camundongos , Movimento Celular/efeitos dos fármacos , Antígeno Prostático Específico/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
Intracerebral hemorrhage (ICH) could trigger inflammatory responses. However, the specific role of inflammatory proteins in the pathological mechanism, complications, and prognosis of ICH remains unclear. In this study, we investigated the expression of 92 plasma inflammation-related proteins in patients with ICH (n = 55) and healthy controls (n = 20) using an Olink inflammation panel and discussed the relation to the severity of stroke, clinical complications, 30-day mortality, and 90-day outcomes. Our result showed that six proteins were upregulated in ICH patients compared with healthy controls, while seventy-four proteins were downregulated. In patients with ICH, seven proteins were increased in the severe stroke group compared with the moderate stroke group. In terms of complications, two proteins were downregulated in patients with pneumonia, while nine proteins were upregulated in patients with sepsis. Compared with the survival group, three proteins were upregulated, and one protein was downregulated in the death group. Compared with the good outcome group, eight proteins were upregulated, and four proteins were downregulated in the poor outcome group. In summary, an in-depth exploration of the differential inflammatory factors in the early stages of ICH could deepen our understanding of the pathogenesis of ICH, predict patient prognosis, and explore new treatment strategies.