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BACKGROUND: The role of miR-145-5p in non-small cell lung cancer (NSCLC) has been studied, however, the regulation of hBMSCs-derived exosomes (Exo) transmitted miR-145-5p in NSCLC was still unknown. This study aimed to investigate the role of hBMSCs-derived exosomes (Exo) in the progression of NSCLC. METHODS: The Exo was extracted from hBMSCs and added to A549 and H1299 cell culture, followed by the detection of cell proliferation, migration, and invasion. The correlation between the expression of miR-145-5p and SOX9, as well as their binding relationship was determined by correlation analysis, luciferase gene reporter assay and RNA pull-down assays. The in vivo animal model was established to further verify the impact of hBMSCs-Exo. RESULTS: It showed that miR-145-5p was downregulated and SOX9 was upregulated in NSCLC tissues. HBMSCs-derived Exo, and hBMSCs-Exo with overexpression of miR-145-5p could inhibit cell proliferation, migration, and invasion of both A549 and H1299 cells, and prevent against tumor progression in vivo. MiR-145-5p and SOX9 were found to be able to bind to each other, and a negative correlation were observed between the expression of them in NSCLC tissues. Furthermore, inhibition of SOX9 could reversed the suppressed role of miR-145-5p in vitro and in vivo. CONCLUSION: Therefore, HBMSCs-Exo effectively transmitted miR-145-5p, leading to the suppression of malignant development in NSCLC through the regulation of SOX9.
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Carcinoma Pulmonar de Células não Pequenas , Movimento Celular , Proliferação de Células , Exossomos , Neoplasias Pulmonares , Células-Tronco Mesenquimais , MicroRNAs , Fatores de Transcrição SOX9 , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Fatores de Transcrição SOX9/metabolismo , Fatores de Transcrição SOX9/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Animais , Exossomos/metabolismo , Exossomos/genética , Camundongos , Proliferação de Células/genética , Células-Tronco Mesenquimais/metabolismo , Movimento Celular/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Masculino , Feminino , Células A549 , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Lily bulbs, which have both nutrient storage and reproductive functions, are a representative group of plants for studying the maintenance and transfer of plant-associated microbiomes. In this study, a comparison of the microbial composition of bulbs and their regenerated seedlings cultured under aseptic conditions, as well as subcultured seedlings that succeeded five times, was examined by amplicon sequencing. A total of 62 bacterial taxa and 56 fungal taxa were found to be transferred to the 5th generation in seedlings, which are the core microbiome of lily. After the regeneration of seedlings from bulbs, there was a significant increase in the number of detectable microbial species, and after 1, 3, and 5 successive generations, there was a decrease in the number of detectable species. Interestingly, some "new" microorganisms appeared in each generation of samples; for instance, 167 and 168 bacterial operational taxonomic units (OTUs) in the 3rd and 5th generations of seedlings that were not detected in either bulbs or seedlings of the previous two generations. These results suggest that bulbs can maintain a high diversity of microorganisms, including some with ultra-low abundance, and have a high transfer capacity to tuck shoots through continuous subculture. The diversity and maintenance of the microbiome can provide the necessary microbial reservoir support for regenerating seedlings. This habit of maintaining low abundance and high diversity may be biologically and ecologically critical for maintaining microbiome stability and function due to the sequestration nature of the plant.
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BACKGROUND: Macrophage activation syndrome (MAS), an example of secondary hemophagocytic lymphohistiocytosis, is a potentially fatal complication of rheumatic diseases. We aimed to study the clinical and laboratory characteristics, treatment schemes, and outcomes of different rheumatic disorders associated with MAS in children. Early warning indicators of MAS have also been investigated to enable clinicians to make a prompt and accurate diagnosis. METHODS: Fifty-five patients with rheumatic diseases complicated by MAS were enrolled between January 2017 and December 2022. Clinical and laboratory data were collected before disease onset, at diagnosis, and after treatment with MAS, and data were compared between patients with systemic juvenile idiopathic arthritis (sJIA), Kawasaki disease (KD), and systemic lupus erythematosus (SLE). A random forest model was established to show the importance score of each variable with a significant difference. RESULTS: Most (81.8%) instances of MAS occurred during the initial diagnosis of the underlying disease. Compared to the active stage of sJIA, the platelet count, erythrocyte sedimentation rate, and fibrinogen level in sJIA-MAS were significantly decreased, whereas ferritin, ferritin/erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and D-dimer levels were significantly increased. Ferritin level, ferritin/erythrocyte sedimentation rate, and platelet count had the greatest predictive value for sJIA-MAS. The level of IL-18 in the sJIA-MAS group was significantly higher than in the active sJIA group, whereas IL-6 levels were significantly lower. Most patients with MAS were treated with methylprednisolone pulse combined with cyclosporine, and no deaths occurred. CONCLUSIONS: Thrombocytopenia, ferritin levels, the ferritin/erythrocyte sedimentation rate, and elevated aspartate aminotransferase levels can predict the occurrence of MAS in patients with sJIA. Additionally, our analysis indicates that IL-18 plays an important role in the pathogenesis of MAS in sJIA-MAS.
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Artrite Juvenil , Síndrome de Ativação Macrofágica , Humanos , Síndrome de Ativação Macrofágica/etiologia , Síndrome de Ativação Macrofágica/diagnóstico , Masculino , Feminino , Criança , Artrite Juvenil/complicações , Pré-Escolar , Adolescente , Ferritinas/sangue , Lúpus Eritematoso Sistêmico/complicações , Sedimentação Sanguínea , Estudos Retrospectivos , Contagem de Plaquetas , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/sangueRESUMO
INTRODUCTION: Over the decades the trends of early onset of puberty have been observed in children, particularly in girls. Research evidence has reported diet to be among the most important risk factors for puberty onset. This study evaluated the association between dietary behavior and puberty in girls. METHODS: We enrolled 201 girls with the main complaints of breast development as the cases at the Endocrine Department of Nanjing Children's Hospital. The cases were divided into breast development with central priming and breast development without central priming groups and were matched with 223 normal health girls with no breast development (control group). We used the modified Child Eating Behavior Questionnaire (CEBQ) to conduct a face-to-face interview about dietary behavior. Sample t-test or Mann Whitney U test or Chi-square test, the analysis of variance or Kruskal Wallis test, and least significant difference (LSD) were used to compare differences between the groups, Bonferroni was used to correct the p-value, and logistic regression was used to analyze risk factors for puberty onset. RESULTS: A total of 424 girls participated in this study, among them, 136 were cases with breast development with central priming, 65 were cases with breast development without central priming, and 223 were normal health girls with no breast development. Age of the participants ranged from 4.5 to 9.3 years. There were significant differences in food response (p < 0.001), dietary restriction (p < 0.001), frequencies of vegetable intake (χ2 = 8.856, p = 0.012), drinking milk (χ2 = 23.099, p = 0.001), and borderline statistical difference in a total score of unhealthy dietary behavior (p = 0.053) among the cases and controls. However, in the post hoc analysis, these dietary behaviors were significant differences between the girls with breast development with central priming and the control groups. Moreover, girls in the breast development with central priming group had significantly higher bone age (BA), uterine body length, ovarian volume, basal luteinizing hormone (LH), basal follicle-stimulating hormone (FSH), peak LH, peak FSH, estradiol (E2), and free triiodothyronine (FT3) compared to those in the breast development without central priming group. In the multivariate logistic regression, only uterine body length was associated with increased risk of breast development with central priming (OR = 1.516, 95%CI: 1.243-1.850). CONCLUSION: There were significant differences in dietary behaviors among girls with breast development with central priming and normal health girls with no breast development, and uterine body length was associated with an increasing risk of breast development with central priming among girls with breast development.
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Comportamento Alimentar , Puberdade , Humanos , Feminino , Criança , Puberdade/fisiologia , Estudos de Casos e Controles , Fatores de Risco , Pré-Escolar , Dieta , Puberdade Precoce/epidemiologia , Puberdade Precoce/etiologia , Modelos Logísticos , Mama/crescimento & desenvolvimentoRESUMO
AIM: To gain insights into the global research hotspots and trends of myopia. METHODS: Articles were downloaded from January 1, 2013 to December 31, 2022 from the Science Core Database website and were mainly statistically analyzed by bibliometrics software. RESULTS: A total of 444 institutions in 87 countries published 4124 articles. Between 2013 and 2022, China had the highest number of publications (n=1865) and the highest H-index (61). Sun Yat-sen University had the highest number of publications (n=229) and the highest H-index (33). Ophthalmology is the main category in related journals. Citations from 2020 to 2022 highlight keywords of options and reference, child health (pediatrics), myopic traction mechanism, public health, and machine learning, which represent research frontiers. CONCLUSION: Myopia has become a hot research field. China and Chinese institutions have the strongest academic influence in the field from 2013 to 2022. The main driver of myopic research is still medical or ophthalmologists. This study highlights the importance of public health in addressing the global rise in myopia, especially its impact on children's health. At present, a unified theoretical system is still needed. Accurate surgical and therapeutic solutions must be proposed for people with different characteristics to manage and intervene refractive errors. In addition, the benefits of artificial intelligence (AI) models are also reflected in disease monitoring and prediction.
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Four new tirucallane-type triterpenoids, polystanins H-K (1-4), were obtained from the stems and leaves of Aphanamixis polystachya. Their structures were elucidated by analysis of the spectroscopic data and comparison with literature data. Compounds 1 and 2 showed week inhibitory effects against NO production in LPS-stimulated RAW264.7 cells. All the isolates were investigated for their antifungal activities against drug-resistant Candida albicans.
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Antifúngicos , Candida albicans , Óxido Nítrico , Triterpenos , Triterpenos/química , Triterpenos/farmacologia , Triterpenos/isolamento & purificação , Camundongos , Animais , Estrutura Molecular , Candida albicans/efeitos dos fármacos , Células RAW 264.7 , Óxido Nítrico/biossíntese , Óxido Nítrico/antagonistas & inibidores , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Folhas de Planta/química , Testes de Sensibilidade Microbiana , Lipopolissacarídeos/farmacologia , Meliaceae/química , Caules de Planta/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificaçãoRESUMO
Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.
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Neoplasias Associadas a Colite , Progressão da Doença , Macrófagos , Humanos , Macrófagos/patologia , Neoplasias Associadas a Colite/patologia , Neoplasias Associadas a Colite/tratamento farmacológico , Neoplasias Colorretais/patologia , Animais , Colite Ulcerativa/patologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/complicaçõesRESUMO
During a routine physical examination three years ago, a 47-year-old woman received a diagnosis of a nodule in her right upper lung. Since then, she has been regularly attending outpatient clinic appointments for follow-up. Over time, the nodule has shown gradual growth, leading to a suspicion of lung cancer. Through the use of enhanced CT imaging, a three-dimensional reconstruction was performed to examine the bronchi and blood vessels in the patient's chest. This reconstruction revealed several variations in the anatomy of the anterior segment of the right upper lobe. Specifically, the anterior segmental bronchus (B3) was found to have originated from the right middle lung bronchus. Additionally, the medial subsegmental artery of the anterior segmental artery (A3b) and the medial segmental artery (A5) were observed to share a common trunk. As for the lateral subsegmental artery of the anterior segmental artery (A3a), it was found to have originated from the right inferior pulmonary trunk. Furthermore, the apical subsegmental artery of the apical segmental artery (A1a) and the posterior segmental artery (A2) were found to have a shared trunk.
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Neoplasias Pulmonares , Pulmão , Humanos , Feminino , Pessoa de Meia-Idade , Pulmão/irrigação sanguínea , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/anatomia & histologia , Brônquios/diagnóstico por imagem , Brônquios/anatomia & histologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , TóraxRESUMO
INTRODUCTION: Autoimmune encephalitis (AE) is a rare, treatable disease of the central nervous system (CNS) caused by an antibody-related immune response. This study is to investigate the correlation of clinical features, cerebrospinal fluid (CSF) characteristics, and prognosis in patients with AE. METHODS: A total of 71 patients diagnosed with antibody-positive AE were retrospectively analyzed. The patients were divided into three groups: anti-NMDAR group, anti-LGI1 group, and other types. Clinical data were collected to analyze clinical features and CSF results, and prognosis was determined by modified Rankin Scale (mRS). RESULTS: There was statistical difference in the incidences of decreased consciousness level (P < 0.001), memory loss (P = 0.017), speech disorders (P = 0.035), and dyskinesia (P = 0.001) in different antibodies groups. Younger age (P = 0.018), elevated CSF chloride content (P = 0.006), and white blood cells > 50/mm3 (P = 0.026) were highly correlated with ICU admission. Anti-LGI1 encephalitis had a relatively small risk for ICU admission (P = 0.034), and a lower risk of poor functional recovery (P = 0.048) and recurrence (P = 0.041). Patients with first-line treatment failure (P = 0.021) had an increased risk of poor functional recovery. Delayed treatment (P = 0.011) would increase the risk of recurrence. CONCLUSION: There are differences in age, gender, clinical characteristics, and CSF results in different subtypes of AE. First-line therapy failure would have poor functional recovery, and delayed therapy would increase the risk of relapse. Chloride ion content and white blood cell count in cerebrospinal fluid are positively correlated with the patient's exacerbation and admission to ICU. These indicators have certain clinical value for the prognosis of AE patients.
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PURPOSE: This study seeks to build a normative database for the vessel density of the superficial retina (SVD) and evaluate how changes and trends in the retinal microvasculature may be influenced by age and axial length (AL) in non-glaucomatous eyes, as measured with optical coherence tomography angiography (OCTA). METHODS: We included 500 eyes of 290 healthy subjects visiting a county hospital. Each participant underwent comprehensive ophthalmological examinations and OCTA to measure the SVD and thickness of the macular and peripapillary areas. To analyze correlations between SVD and age or AL, multivariable linear regression models with generalized estimating equations were applied. RESULTS: Age was negatively correlated with the SVD of the superior, central, and inferior macular areas and the superior peripapillary area, with a decrease rate of 1.06%, 1.36%, 0.84%, and 0.66% per decade, respectively. However, inferior peripapillary SVD showed no significant correlation with age. AL was negatively correlated with the SVD of the inferior macular area and the superior and inferior peripapillary areas, with coefficients of -0.522%/mm, -0.733%/mm, and -0.664%/mm, respectively. AL was also negatively correlated with the thickness of the retinal nerve fiber layer and inferior ganglion cell complex (p = 0.004). CONCLUSION: Age and AL were the two main factors affecting changes in SVD. Furthermore, AL, a relative term to represent the degree of myopia, had a greater effect than age and showed a more significant effect on thickness than on SVD. This relationship has important implications because myopia is a significant issue in modern cities.
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Miopia , Vasos Retinianos , Humanos , Retina , Tomografia de Coerência Óptica/métodos , Fibras Nervosas , EnvelhecimentoRESUMO
Background: Previous studies showed that per- and polyfluoroalkyl substances (PFAS), which are widely found in the environment, can disrupt endocrine homeostasis when they enter the human body. This meta-analysis aimed to evaluate current human epidemiological evidence on the relationship between PFAS exposure and glucolipid metabolism in childhood and adolescence. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Library databases, and identified population-based epidemiological studies related to PFAS and glucolipid metabolism indexes that were published before 30 December 2022. The heterogeneity of the included literature was assessed using the I-square (I2) test and statistics Q. Random-effects and fixed-effects models were used to combine the effect size. Subgroup analysis based on age and sex of the study participants was performed. A sensitivity analysis was used to evaluate the robustness and reliability of the combined results. Egger's and Begg's tests were used to analyze publication bias. Results: A total of 12 studies were included in this analysis. There was a positive association between PFAS and TC (ß = 1.110, 95% CI: 0.601, 1.610) and LDL (ß = 1.900, 95% CI: 1.030, 2.770), and a negative association between PFAS and HOMA-IR in children and adolescents (ß = -0.130, 95% CI: -0. 200, -0.059). PFOS was significant positive associated with TC (ß = 8.22, 95% CI: 3.93, 12.51), LDL (ß = (12.04, 95% CI: 5.08, 18.99), and HOMA-IR (ß = -0.165, 95% CI: -0.292, -0.038). Subgroup analysis showed that exposure to PFAS in the adolescent group was positively associated with TC and LDL levels, and the relationship was stronger in females. Conclusion: PFAS exposure is associated with glucolipid metabolism in children and adolescents. Among them, PFOS may play an important role. Recognition of environmental PFAS exposure is critical for stabilizing the glycolipid metabolism relationship during the growth and development of children and adolescents.
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Fluorocarbonos , Metabolismo dos Lipídeos , Adolescente , Criança , Feminino , Humanos , Bases de Dados Factuais , Fluorocarbonos/toxicidade , Homeostase , Reprodutibilidade dos Testes , MasculinoRESUMO
Objective: This study aims to evaluate inpatient services in 49 tertiary comprehensive hospitals using indicators from the diagnosis related groups (DRG) payment system. Method: DRG data from 49 tertiary comprehensive hospitals were obtained from the quality monitoring platform for provincial hospitals, and relevant indicators were identified. The analytic hierarchy process (AHP) was used to compute the weight of each indicator. The rank sum ratio method was used to calculate the weight rank sum ratio (WRSR) value and the corresponding probit value of each hospital. The hospitals were divided into four grades based on the threshold value: excellent, good, fair, and poor. Results: Eight indicators of the 49 hospitals were scored, and the hospital rankings of indicators varied. The No. 1 hospital ranked first in the indicators of "total number of DRG", "number of groups", and "proportion of relative weights (RW) ≥ 2". The WRSR value of the No.1 hospital was the largest (0.574), and the WRSR value of the No. 44 hospital was the smallest (0.139). The linear regression equation was established: WRSRpredicted =-0.141+0.088*Probit, and the regression model was well-fitted (F = 2066.672, p < 0.001). The cut-off values of the three WRSRspredicted by the four levels were 0.167, 0.299, and 0.431, respectively. The 49 hospitals were divided into four groups: excellent (4), good (21), average (21), and poor (3). There were significant differences in the average WRSR values of four categories of hospitals (p < 0.05). Conclusion: There were notable variances in the levels of inpatient services among 49 tertiary comprehensive hospitals, and hospitals of the same category also showed different service levels. The evaluation results contribute to the health administrative department and the hospital to optimize the allocation of resources, improve the DRG payment system, and enhance the quality and efficiency of inpatient services.
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Grupos Diagnósticos Relacionados , Pacientes Internados , Humanos , HospitaisRESUMO
BACKGROUND: Clusters, a novel hierarchical material structure that emerges from atoms or molecules, possess unique reactivity and catalytic properties, crucial in catalysis, biomedicine, and optoelectronics. Predicting cluster energy provides insights into electronic structure, magnetism, and stability. However, the structure of clusters and their potential energy surface is exceptionally intricate. Searching for the global optimal structure (the lowest energy) among these isomers poses a significant challenge. Currently, modelling cluster energy predictions with traditional machine learning methods has several issues, including reliance on manual expertise, slow computation, heavy computational resource demands, and less efficient parameter tuning. RESULTS: This paper introduces a predictive model for the energy of a gold cluster comprising twenty atoms (referred to as Au20 cluster). The model integrates the Multiple Strategy Fusion Whale Optimization Algorithm (MSFWOA) with the Light Gradient Boosting Machine (LightGBM), resulting in the MSFWOA-LightGBM model. This model employs the Coulomb matrix representation and eigenvalue solution methods for feature extraction. Additionally, it incorporates the Tent chaotic mapping, cosine convergence factor, and inertia weight updating strategy to optimize the Whale Optimization Algorithm (WOA), leading to the development of MSFWOA. Subsequently, MSFWOA is employed to optimize the parameters of LightGBM for supporting the energy prediction of Au20 cluster. CONCLUSIONS: The experimental results show that the most stable Au20 cluster structure is a regular tetrahedron with the lowest energy, displaying tight and uniform atom distribution, high geometric symmetry. Compared to other models, the MSFWOA-LightGBM model excels in accuracy and correlation, with MSE, RMSE, and R2 values of 0.897, 0.947, and 0.879, respectively. Additionally, the MSFWOA-LightGBM model possesses outstanding scalability, offering valuable insights for material design, energy storage, sensing technology, and biomedical imaging, with the potential to drive research and development in these areas.
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AIMS: This study aimed to (i) evaluate the effectiveness of mindfulness-based interventions in improving self-efficacy, reducing stress and anxiety among peritoneal dialysis patients, and (ii) compare the most effective method of mindfulness based interventions. METHODS: This randomized three-arm controlled trial recruited first-time peritoneal dialysis patients from the peritoneal dialysis outpatient clinic in Singapore. Patients were randomly allocated to either video-assisted mindfulness training, therapist-assisted mindfulness training or treatment-as-usual. All groups received 4.5 days of structured peritoneal dialysis training at the peritoneal dialysis centre, while video-assisted mindfulness training and therapist-assisted mindfulness training groups were taught additional mindfulness-based techniques. The perceived stress scale, self-efficacy, and anxiety (State and Trait Anxiety Inventory) were measured at baseline, 4- and 12 weeks post-randomization, using reliable and valid instruments. RESULTS: Thirty-nine patients were recruited (13 in each group). All the therapies showed a significant time trend in anxiety. Only therapist- and video-assisted mindfulness training showed a significant trend in perceived stress scale scores but not treatment-as-usual. All Intervention X Time interactions were not significant. Patients in therapist- and video-assisted mindfulness training groups had reduced perceived stress scale scores compared to treatment-as-usual at week 12. CONCLUSION: This study demonstrated the potential of mindfulness-based interventions in reducing stress among first-time PD patients.
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Atenção Plena , Diálise Peritoneal , Testes Psicológicos , Autorrelato , Humanos , Atenção Plena/métodos , Singapura , Instituições de Assistência Ambulatorial , TecnologiaRESUMO
Copper-catalyzed selective alkynylation with N-propargyl carboxamides as nucleophiles has been successfully developed for the synthesis of C2-functionalized chromanones. Under optimized reaction conditions, 21 examples were obtained in one-pot procedure through 1,4-conjugate addition. This protocol features readily available feedstocks, easy operations, and moderate to good yields, which provides viable access to pharmacologically active C2-functionalized chromanones.
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Cromonas , Cobre , Estrutura Molecular , CatáliseRESUMO
BACKGROUND: DNA methylation is a form of epigenetic modification that impacts gene expression without modifying the DNA sequence, thereby exerting control over gene function and cellular development. The prediction of DNA methylation is vital for understanding and exploring gene regulatory mechanisms. Currently, machine learning algorithms are primarily used for model construction. However, several challenges remain to be addressed, including limited prediction accuracy, constrained generalization capability, and insufficient learning capacity. RESULTS: In response to the aforementioned challenges, this paper leverages the similarities between DNA sequences and time series to introduce a time series-based hybrid ensemble learning model, called Multi2-Con-CAPSO-LSTM. The model utilizes multivariate and multidimensional encoding approach, combining three types of time series encodings with three kinds of genetic feature encodings, resulting in a total of nine types of feature encoding matrices. Convolutional Neural Networks are utilized to extract features from DNA sequences, including temporal, positional, physicochemical, and genetic information, thereby creating a comprehensive feature matrix. The Long Short-Term Memory model is then optimized using the Chaotic Accelerated Particle Swarm Optimization algorithm for predicting DNA methylation. CONCLUSIONS: Through cross-validation experiments conducted on 17 species involving three types of DNA methylation (6 mA, 5hmC, and 4mC), the results demonstrate the robust predictive capabilities of the Multi2-Con-CAPSO-LSTM model in DNA methylation prediction across various types and species. Compared with other benchmark models, the Multi2-Con-CAPSO-LSTM model demonstrates significant advantages in sensitivity, specificity, accuracy, and correlation. The model proposed in this paper provides valuable insights and inspiration across various disciplines, including sequence alignment, genetic evolution, time series analysis, and structure-activity relationships.
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Metilação de DNA , Redes Neurais de Computação , Fatores de Tempo , Algoritmos , Aprendizado de MáquinaRESUMO
Biological sequence data mining is hot spot in bioinformatics. A biological sequence can be regarded as a set of characters. Time series is similar to biological sequences in terms of both representation and mechanism. Therefore, in the article, biological sequences are represented with time series to obtain biological time sequence (BTS). Hybrid ensemble learning framework (SaPt-CNN-LSTM-AR-EA) for BTS is proposed. Single-sequence and multi-sequence models are respectively constructed with self-adaption pre-training one-dimensional convolutional recurrent neural network and autoregressive fractional integrated moving average fused evolutionary algorithm. In DNA sequence experiments with six viruses, SaPt-CNN-LSTM-AR-EA realized the good overall prediction performance and the prediction accuracy and correlation respectively reached 1.7073 and 0.9186. SaPt-CNN-LSTM-AR-EA was compared with other five benchmark models so as to verify its effectiveness and stability. SaPt-CNN-LSTM-AR-EA increased the average accuracy by about 30%. The framework proposed in this article is significant in biology, biomedicine, and computer science, and can be widely applied in sequence splicing, computational biology, bioinformation, and other fields.
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Algoritmos , Aprendizagem , Fatores de Tempo , Sequência de Bases , Aprendizado de MáquinaRESUMO
With the upsurge of artificial intelligence (AI) technology in the medical field, its application in ophthalmology has become a cutting-edge research field. Notably, machine learning techniques have shown remarkable achievements in diagnosing, intervening, and predicting ophthalmic diseases. To meet the requirements of clinical research and fit the actual progress of clinical diagnosis and treatment of ophthalmic AI, the Ophthalmic Imaging and Intelligent Medicine Branch and the Intelligent Medicine Committee of Chinese Medicine Education Association organized experts to integrate recent evaluation reports of clinical AI research at home and abroad and formed a guideline on clinical research evaluation of AI in ophthalmology after several rounds of discussion and modification. The main content includes the background and method of developing this guideline, an introduction to international guidelines on the clinical research evaluation of AI, and the evaluation methods of clinical ophthalmic AI models. This guideline introduces general evaluation methods of clinical ophthalmic AI research, evaluation methods of clinical ophthalmic AI models, and commonly-used indices and formulae for clinical ophthalmic AI model evaluation in detail, and amply elaborates the evaluation methods of clinical ophthalmic AI trials. This guideline aims to provide guidance and norms for clinical researchers of ophthalmic AI, promote the development of regularization and standardization, and further improve the overall level of clinical ophthalmic AI research evaluations.
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BACKGROUND: Cyclophosphamide (CTX) and calcineurin inhibitors (CNIs) based regimens are recommended as immunosuppressive therapies for patients with idiopathic membranous nephropathy (IMN). Focal and segmental glomerular sclerosis (FSGS) lesions, which are common in membranous nephropathy (MN), are poor predictors of outcome. This study compared the differences of prognosis between two regimens in patients with IMN combined with FSGS lesions. METHODS: This retrospective study enrolled 108 patients with biopsy-proven IMN, accompanied with FSGS lesions, nephrotic syndrome and an estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m2 who were treated with CTX or CNIs. We used propensity score matching (PSM) for balancing the confounding variables. RESULTS: During follow-up, 10 patients (10/55 [18.2%]; nine males) in the CNIs group showed a 50% decline in eGFR; eight had a not otherwise specified variant. Patients initially treated with CNIs had a significantly higher risk of progression to the primary outcome and a lower probability of complete or total remission. The relapse rate was higher in patients who initially received CNIs- than in those who received CTX-based treatment. Before PSM, age and 24-h urine protein level differed significantly between the groups. The PSM model included data from 72 patients. Worse outcomes were also noted among patients who initially received CNIs than those who received CTX-based treatments after matching. CONCLUSIONS: Patients with MN combined with FSGS lesions have a higher risk of renal functional decline and a higher rate of relapse after CNIs than after CTX therapy.
Assuntos
Glomerulonefrite Membranosa , Glomerulosclerose Segmentar e Focal , Masculino , Humanos , Adulto Jovem , Adulto , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/complicações , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Estudos Retrospectivos , Inibidores de Calcineurina/uso terapêutico , Ciclofosfamida/uso terapêutico , ChinaRESUMO
BACKGROUND: Childhood obesity became a severe public health challenge, and insulin resistance (IR) was one of the common complications. Both obesity and IR were considered as the basis of metabolic disorders. However, it is unclear which common key metabolites are associated with childhood obesity and IR. METHODS: The children were divided into normal weight and overweight/obese groups. Fasting blood glucose and fasting insulin were measured, and homeostasis model assessment of insulin resistance was calculated. Liquid chromatography-tandem mass spectrometry was applied for metabonomic analysis. Multiple linear regression analysis and correlation analysis explored the relationships between obesity, IR, and metabolites. Random forests were used to rank the importance of differential metabolites, and relative operating characteristic curves were used for prediction. RESULTS: A total of 88 normal-weight children and 171 obese/overweight children participated in the study. There was a significant difference between the two groups in 30 metabolites. Childhood obesity was significantly associated with 10 amino acid metabolites and 20 fatty acid metabolites. There were 12 metabolites significantly correlated with IR. The ranking of metabolites in random forest showed that glutamine, tyrosine, and alanine were important in amino acids, and pyruvic-ox-2, ethylmalonic-2, and phenyllactic-2 were important in fatty acids. The area under the curve of body mass index standard deviation score (BMI-SDS) combined with key amino acid metabolites and fatty acid metabolites for predicting IR was 80.0% and 76.6%, respectively. CONCLUSIONS: There are common key metabolites related to IR and obese children, and these key metabolites combined with BMI-SDS could effectively predict the risk of IR.