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Systemic Lupus Erythematosus (SLE) is an autoimmune sickness with unclear pathogenesis. The goal of this research was to reveal the heterogeneity of immune cells in SLE patients of Han and Zang nationality by single-cell RNA sequencing (scRNA-seq) and bioinformatics profiling. METHODS: A total of 94,102 peripheral blood mononuclear cells (PBMCs) from six volunteers with SLE (3 Zang, 3 Han) and six healthy controls were first conducted through scRNA-seq analysis. The immune cell subsets in the pathogenesis of SLE were analyzed as well. Real-time quantitative PCR (RT-qPCR) was applied to confirm the results of sc-RNA seq analysis. RESULTS: For the Tibetan samples, the ratios of Naïve CD4 RPS4Y1 cells, Naïve CD4 cells, Memory BC CD24 and Memory BC differed significantly between the SLE and control samples, while that of CD8 CTL MAL cells was significantly different between the two groups in Han nationality samples. Variable differentiation states of CD8 CTL MAL cells, CD8 CTL GZMK cells, and Naïve CD4 cells were detected through pseudotime analysis. Moreover, T-cell receptor (TCR) abundance was notably higher in Tibetan SLE specimens than that in controls, while B-cell receptor (BCR) abundance in Tibetan and Han samples was higher than in control groups. CONCLUSIONS: In summary, the immune cellular heterogeneity of SLE patients both Han and Zang nationality was explored based on various bioinformatics approaches, providing new perspectives for immunological characteristics of SLE among different ethnic groups.
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Leucocitos Mononucleares , Lupus Eritematoso Sistémico , Humanos , Diferenciación Celular , Etnicidad , Lupus Eritematoso Sistémico/genética , Análisis de Secuencia de ARNRESUMEN
BACKGROUND: Systemic lupus erythematosus is an immunologically dysregulated disease characterized by the presence of multiple autoantibodies. In SLE, B lymphocytes contribute to the dysregulated production of autoantibodies and cytokines. Recently, we discovered that miR-99a-3p binds to both EIF4EBP1 and NCAPG mRNA and that lowering miR-99a-3p can promote B cell autophagy in SLE by increasing EIF4EBP1 expression. However, the functions of miR-99a-3p and NCAPG in SLE have not been extensively investigated. OBJECTIVE: This work aims to evaluate the levels of miR-99a-3p and NCAPG expression in SLE B cells and to determine whether the aberrant expression of miR-99a-3p and NCAPG contributes to the pathological mechanisms in SLE. METHODS: B lymphocytes were obtained through immunomagnetic negative selection. Using RT-qPCR, miR-99a-3p and NCAPG mRNA expressions in B lymphocytes and in the BALL-1 cell line were measured. To determine the relative abundance of NCAPG, PI3K, p-PI3K, AKT, and p-AKT, we normalize them to the level of ß-actin using Western blotting. Evaluation of miR-99a-3p and NCAPG's impact on cell proliferation was done utilizing CCK-8 assay. Using flow cytometry, the cell cycle and apoptosis were both measured. RESULTS: Comparing SLE B cells to healthy controls, miR-99a-3p expression was significantly downregulated. Additionally, it was observed that SLE B cells had significantly higher NCAPG mRNA expression. Blocking miR-99a-3p expression in BALL-1 cells with an antagomir elevated NCAPG expression, facilitated PI3K/AKT pathway activation, improved cell proliferation, raised the fraction of S-phase cells, and prevented cell apoptosis. The opposite effects of upregulated miR-99a-3p levels on BALL-1 cells were observed by using an agomir. Furthermore, the effect of decreased miR-99a-3p expression on cell proliferation was partially mediated by elevating NCAPG levels and activating the PI3K/AKT pathway. CONCLUSION: Our research indicates that lower miR-99a-3p expression in SLE B cells appears to boost B cell number via the NCAPG and PI3K/AKT pathways.
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Lupus Eritematoso Sistémico , MicroARNs , Humanos , Autoanticuerpos/farmacología , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/farmacología , Proliferación Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , ARN Mensajero , Transducción de SeñalRESUMEN
This study aims to develop a super-resolution (SR) algorithm tailored specifically for enhancing the image quality and resolution of early cervical cancer (CC) magnetic resonance imaging (MRI) images. The proposed method is subjected to both qualitative and quantitative analyses, thoroughly investigating its performance across various upscaling factors and assessing its impact on medical image segmentation tasks. The innovative SR algorithm employed for reconstructing early CC MRI images integrates complex architectures and deep convolutional kernels. Training is conducted on matched pairs of input images through a multi-input model. The research findings highlight the significant advantages of the proposed SR method on two distinct datasets at different upscaling factors. Specifically, at a 2× upscaling factor, the sagittal test set outperforms the state-of-the-art methods in the PSNR index evaluation, second only to the hybrid attention transformer, while the axial test set outperforms the state-of-the-art methods in both PSNR and SSIM index evaluation. At a 4× upscaling factor, both the sagittal test set and the axial test set achieve the best results in the evaluation of PNSR and SSIM indicators. This method not only effectively enhances image quality, but also exhibits superior performance in medical segmentation tasks, thereby providing a more reliable foundation for clinical diagnosis and image analysis.
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Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Neoplasias del Cuello Uterino , Neoplasias del Cuello Uterino/diagnóstico por imagen , Humanos , Femenino , Procesamiento de Imagen Asistido por Computador/métodos , AlgoritmosRESUMEN
BACKGROUND: There are no standards for evaluating skin photoaging. Dermoscopy is a non-invasive detection method that might be useful for evaluating photoaging. OBJECTIVE: To assess the correlation between the dermoscopic evaluation of photoaging and clinical and pathological evaluations. METHODS: The age, clinical evaluation (Fitzpatrick classification, Glogau Photoaging Classification, and Chung's standardized image ruler), histopathology (Masson staining and MMP-1 immunohistochemistry), and dermoscopy (Hu's and Isik's) of 40 donor skin samples were analyzed statistically, and Spearman rank correlation analysis was performed. RESULTS: There was a robust correlation between the total Hu scores and Isik dermoscopy. The correlation of dermoscopy with histopathology was higher than that of clinical evaluation methods. There is a strong correlation between telangiectases and lentigo. Xerosis, superficial wrinkle, diffuse erythema, telangiectases, and reticular pigmentation were significantly correlated with the three clinical evaluation methods. Superficial wrinkles were correlated with Masson, MMP-1, various clinical indicators, and other dermoscopic items. CONCLUSION: There is a good correlation between dermoscopy and clinical and histopathological examination. Dermoscopy might help evaluate skin photoaging.
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Lentigo , Envejecimiento de la Piel , Neoplasias Cutáneas , Telangiectasia , Humanos , Metaloproteinasa 1 de la Matriz , Dermoscopía/métodos , Telangiectasia/diagnóstico por imagen , Neoplasias Cutáneas/patologíaRESUMEN
Photoaging is unique to the skin and is accompanied by an increased risk of tumors. To explore the transcriptomic regulatory mechanism of skin photoaging, the epidermis, and dermis of 16 healthy donors (eight exposed and eight non-exposed) were surgically excised and detected using total RNA-Seq. Weighted gene co-expression network analysis (WGCNA) identified the most relevant modules with exposure. The hub genes were identified using correlation, p-value, and enrichment analysis. The critical genes were identified using Support Vector Machine-Recursive Feature Elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO) regression, then enriched using single-gene GSEA. A competitive endogenous RNA (ceRNA) network was constructed and validated using qRT-PCR. Compared with non-exposed sites, 430 mRNAs, 168 lncRNAs, and 136 miRNAs were differentially expressed in the exposed skin. WGCNA identified the module MEthistle and 12 intersecting genes from the 71 genes in this module. The enriched pathways were related to muscle. The critical genes were KLHL41, MYBPC2, and ERAP2. Single-gene GSEA identified the Hippo signaling pathway, basal cell carcinoma, cell adhesion molecules, and other pathways. Six miRNAs and 18 lncRNAs related to the critical genes constituted the ceRNA network and were verified using qPCR. The differential expression of KLHL41, MYBPC2, and ERAP2 at the protein level was verified using immunohistochemistry. KLHL41, MYBPC2, and ERAP2 genes are related to skin photoaging. The prediction model based on the three critical genes can indicate photoaging. These critical genes may have a role in skin photoaging by regulating cell growth, intercellular adhesion, and substance metabolism pathways.
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MicroARNs , ARN Largo no Codificante , Humanos , Piel , MicroARNs/genética , Perfilación de la Expresión Génica , Transcriptoma , Redes Reguladoras de Genes , AminopeptidasasRESUMEN
BACKGROUND: The Guangzhou Nutrition and Health Study (GNHS) aims to assess the determinants of metabolic disease in nutritional aspects, as well as other environmental and genetic factors, and explore possible biomarkers and mechanisms with multi-omics integration. METHODS: The population-based sample of adults in Guangzhou, China (baseline: 40-83 years old; n = 5118) was followed up about every 3 years. All will be tracked via on-site follow-up and health information systems. We assessed detailed information on lifestyle factors, physical activities, dietary assessments, psychological health, cognitive function, body measurements, and muscle function. Instrument tests included dual-energy X-ray absorptiometry scanning, carotid artery and liver ultrasonography evaluations, vascular endothelial function evaluation, upper-abdomen and brain magnetic resonance imaging, and 14-d real-time continuous glucose monitoring tests. We also measured multi-omics, including host genome-wide genotyping, serum metabolome and proteome, gut microbiome (16S rRNA sequencing, metagenome, and internal transcribed spacer 2 sequencing), and fecal metabolome and proteome. RESULTS: The baseline surveys were conducted from 2008 to 2015. Now, we have completed 3 waves. The 3rd and 4th follow-ups have started but have yet to end. A total of 5118 participants aged 40-83 took part in the study. The median age at baseline was approximately 59.0 years and the proportion of female participants was about 69.4%. Among all the participants, 3628 (71%) completed at least one on-site follow-up with a median duration of 9.48 years. CONCLUSION: The cohort will provide data that have been influential in establishing the role of nutrition in metabolic diseases with multi-omics.
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INTRODUCTION: The association between extreme birth spacing and adverse outcomes is controversial, and available evidence is fragmented into different classifications of birth spacing. MATERIAL AND METHODS: We conducted a systematic review of observational studies to evaluate the association between birth spacing (i.e., interpregnancy interval and interoutcome interval) and adverse outcomes (i.e., pregnancy complications, adverse birth outcomes). Pooled odds ratios (ORs) with 95%â¯confidence intervals (CI) were calculated using a random-effects model, and the dose-response relationships were evaluated using generalized least squares trend estimation. RESULTS: A total of 129 studies involving 46 874 843 pregnancies were included. In the general population, compared with an interpregnancy interval of 18-23 months, extreme intervals (<6 months and ≥ 60 months) were associated with an increased risk of adverse outcomes, including preterm birth, small for gestational age, low birthweight, fetal death, birth defects, early neonatal death, and premature rupture of fetal membranes (pooled OR range: 1.08-1.56; p < 0.05). The dose-response analyses further confirmed these J-shaped relationships (pnon-linear < 0.001-0.009). Long interpregnancy interval was only associated with an increased risk of preeclampsia and gestational diabetes (pnon-linear < 0.005 and pnon-linear < 0.001, respectively). Similar associations were observed between interoutcome interval and risk of low birthweight and preterm birth (pnon-linear < 0.001). Moreover, interoutcome interval of ≥60 months was associated with an increased risk of cesarean delivery (pooled OR 1.72, 95%â¯CI 1.04-2.83). For pregnancies following preterm births, an interpregnancy interval of 9 months was not associated with an increased risk of preterm birth, according to dose-response analyses (pnon-linear = 0.008). Based on limited evidence, we did not observe significant associations between interpregnancy interval or interoutcome interval after pregnancy losses and risk of small for gestational age, fetal death, miscarriage, or preeclampsia (pooled OR range: 0.76-1.21; p > 0.05). CONCLUSIONS: Extreme birth spacing has extensive adverse effects on maternal and infant health. In the general population, interpregnancy interval of 18-23 months may be associated with potential benefits for both mothers and infants. For women with previous preterm birth, the optimal birth spacing may be 9 months.
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Aborto Espontáneo , Preeclampsia , Complicaciones del Embarazo , Nacimiento Prematuro , Embarazo , Lactante , Recién Nacido , Humanos , Femenino , Resultado del Embarazo , Nacimiento Prematuro/epidemiología , Intervalo entre Nacimientos , Peso al Nacer , Complicaciones del Embarazo/epidemiología , Retardo del Crecimiento Fetal , Madres , Muerte FetalRESUMEN
The aim of the study was to testify the association of dietary resveratrol (RSV) intakes with hip fracture risk in Chinese elderly. This was a 1:1 age- and gender- matched case-control study. Eligible cases were newly diagnosed patients of hip fracture. Dietary assessment was made by a 79-item validated food frequency questionnaire. Habitual RSV intakes were estimated as the sum of trans- and cis- isomers of resveratrol and piceid according to the available database. Multivariable conditional logistic regression was applied to examine the relationship of dietary RSV and RSV-rich foods with hip fracture risk. A total of 1,070 pairs of hip fracture incident cases and controls were recruited and 1,065 were included for analysis. Compared with the lowest group, total RSV in the highest quartile group had significantly reduced hip fracture risk by 66.3% (OR: 0.337, 0.222 ~ 0.571, ptrend < 0.001). Similar findings were observed for cis- and trans-RSV, cis- and trans-Piceid, as well as RSV-rich foods (grapes, apples and nuts) respectively. Subgroup analysis suggested more evident findings among female and less obese participants. Our findings demonstrated that higher habitual RSV intakes and RSV-rich foods, even in a relatively low amount, were associated with reduced risk of hip fracture in Chinese elderly.
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Pueblos del Este de Asia , Fracturas de Cadera , Humanos , Femenino , Anciano , Resveratrol , Estudios de Casos y Controles , Riesgo , Fracturas de Cadera/epidemiología , Fracturas de Cadera/prevención & control , Factores de RiesgoRESUMEN
Herein, we prepared Pt2CeO2 heterojunction nanocluster (HJNS) on multiwalled carbon nanotubes (MWCNTs) in deep eutectic solvents (DESs) which is a special class of ionic liquids. The catalyst was then heat-treated at 400 °C in N2 (refer to Pt2CeO2/CNTs-400). The Pt2CeO2/CNTs-400 catalyst showed remarkably improved electrocatalytic performance towards methanol oxidation reaction (MOR) (839.1 mA mgPt-1) compared to Pt2CeO2/CNTs-500 (620.3 mA mgPt-1), Pt2CeO2/CNTs-300 (459.2 mA mgPt-1), Pt2CeO2/CNTs (641.6 mAmg-1) (the catalyst which has not been heat-treated) and commercial Pt/C (229.9 mAmg-1). Additionally, the Pt2CeO2/CNTs-400 catalyst also showed better CO poisoning resistance (onset potential: 0.47 V) compared to Pt2CeO2/CNTs (0.56 V) and commercial Pt/C (0.58 V). The improved performance of Pt2CeO2/CNTs-400 catalyst is attributed to the addition of appropriate CeO2, which changed the electronic state around the Pt atoms, lowered the d-band of Pt atoms, formed more Ce-O-Pt bonds acting as new active sites, affected the adsorption of toxic intermediates and weakened the dissolution of Pt; on the other hand, with the assistance of thermal treatment at 400 °C, the obtained Pt2CeO2 HJNS expose more new active sites at the interface between Pt and CeO2 to enhance the electrochemical active surface area (ECSA) and the dehydrogenation process of MOR. Thirdly, DES is beneficial to the increase of the effective component Pt(0) in the carbonization process. The study shows a new way to construct high-performance Pt-CeO2 catalyst for the direct methanol fuel cell (DMFC).
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BACKGROUND: Studies have rarely explored the association between oral health status and different sarcopenia groups (possible sarcopenia, diagnosed sarcopenia, and severe sarcopenia). Moreover, these studies have not reported any definitive conclusions of their relationship. We aimed to characterize the oral health status, prevalence of sarcopenia, and risk factors in different sarcopenia groups of elderly outpatients of community hospitals. Furthermore, we determined the correlation among nutrition, oral health, and different sarcopenia groups. METHODS: Overall, 1505 elderly participants (aged ≥ 65 years) completed the survey. The Mini Nutritional Assessment short-form (MNA-SF) was used to assess the nutrition status of the elderly. Oral health was assessed using the instrument of the oral health assessment index of the elderly (General Oral Health Assessment Index [GOHAI]), and the number of remaining natural teeth (NRT) was counted. Data on muscle mass, muscle strength, and gait speed were collected, and sarcopenia was classified into three groups (possible sarcopenia, diagnosed sarcopenia, and severe sarcopenia) according to the Asian Working Group for Sarcopenia 2019. Multinomial logistic regression multivariate analysis was used to test their relationships. RESULTS: Eighty-eight (5.8%) participants were identified as having possible sarcopenia; 142 (9.5%), diagnosed sarcopenia; 136 (9.0%), severe sarcopenia; and 1139 (75.7%), no sarcopenia. Of the seven variables, advancing age was typically associated with an increasing prevalence of sarcopenia (odds ratio [OR] = 1.06-1.47, 95% confidence interval [CI] = 1.06-1.47). The results showed that household income (OR = 0.57, 95% CI = 0.33-0.98), education level (OR = 3.32, 95% CI = 1.09-10.07), and chronic diseases (OR = 0.34, 95% CI = 0.19-0.62) were significantly associated with the severe sarcopenia group. Physical activity scores were significantly associated with the diagnosed sarcopenia and severe sarcopenia groups. Participants with < 20 NRT were more likely to have diagnosed sarcopenia (OR = 5.55, 95% CI = 3.80-8.12) or severe sarcopenia (OR = 6.66, 95% CI = 4.13-10.76) than participants with > 20 NRT. The GOHAI score was associated with the diagnosed sarcopenia (OR = 5.55, 95% CI = 3.80-8.12) and severe sarcopenia (OR = 6.66, 95% CI = 4.13-10.78) groups. The MNA-SF score was associated with the different sarcopenia groups. CONCLUSIONS: Assessing early and improving lifestyle with respect to nutrition and oral health may be an effective way to reduce or delay the occurrence of sarcopenia.
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Salud Bucal , Sarcopenia , Anciano , China , Estudios Transversales , Evaluación Geriátrica/métodos , Hospitales Comunitarios , Humanos , Evaluación Nutricional , Estado Nutricional , Pacientes Ambulatorios , Prevalencia , Sarcopenia/complicaciones , Sarcopenia/diagnóstico , Sarcopenia/epidemiologíaRESUMEN
PURPOSE: The main objective of the study was to translate, validate, and compare the Chinese ORTO scales (ORTO-15 and ORTO-R). The secondary objective was to assess factors that may be related with risk of orthorexia nervosa (ON). METHODS: Two cross-sectional surveys were conducted on March-to-June 2021 for ORTO-15 and April 2022 for ORTO-R. ORTO questionnaires were translated into Chinese using the forward-backward-forward method. Exploratory factor analysis (EFA), discriminant validity and confirmatory factor analysis (CFA) were used to examine the construct validity of the questionnaires. The internal consistency was assessed using the Cronbach alpha coefficient and the test-retest reliability. Multivariate linear regression analysis was used to explore potential factors related with ON scores. RESULTS: Totally, 1289 and 1084 eligible participants were included for assessment of ORTO-15 and ORTO-R, with the mean age of 20.9 ± 2.0 years and 21.0 ± 2.3 years. The internal consistency of Chinese ORTO-15 scale and ORTO-R scale were both satisfactory (α = 0.79, ICC = 0.79; α = 0.77, ICC = 0.82). However, all ORTO-15 models showed a poor fit using CFA whereas the ORTO-R was characterized by acceptable goodness-of-fit. Multivariate linear regression indicated that physical activities and mental disorders were positively associated with ON risk assessed by both ORTO-R and ORTO-15. CONCLUSION: The Chinese ORTO-R scale was a more reliable tool to screen for ON tendencies than the Chinese version of ORTO-15. Mental disorders and physical activities might be associated with the increased ON risk. LEVEL OF EVIDENCE: Level V (descriptive cross-sectional study).
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Trastornos de Alimentación y de la Ingestión de Alimentos , Conductas Relacionadas con la Salud , Humanos , Adolescente , Adulto Joven , Adulto , Ortorexia Nerviosa , Estudios Transversales , Reproducibilidad de los Resultados , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Estudiantes , Encuestas y Cuestionarios , Psicometría/métodosRESUMEN
BACKGROUND: The 2019 coronavirus disease (COVID-19) is a global public health emergency. So far, only a limited number of studies have investigated the impact of the COVID-19 pneumonia pandemic on the mental health of parents having children with cancer. This study investigated the hope, and relevant influencing factors (depression, anxiety, demographic data) among parents whose children had retinoblastoma (RB) during the COVID-19 pandemic. METHODS: A cross-sectional survey and a convenient sampling survey were conducted on 317 parents of RB children admitted to the Ninth People's Hospital affiliated with Shanghai Jiao Tong University, School of Medicine, and Qilu Children's Hospital of Shandong University. The survey tools included Demographic Questionnaire, Herth Hope Index (HHI), The Generalized Anxiety Disorder (GAD-7), and the Patient Health Questionnaires (PHQ)-2. RESULTS: The hope level score of the parents of RB patients was (35.36 ± 4.42), which was at the medium level. The highest dimension of hope score was inner positive readiness and expectancy (12.07 ± 1.57), and the lowest dimension was interconnectedness with self and others (11.50 ± 1.64). The incidence rate of depression and anxiety was 29.97% (95/317) and 41.32% (131/317), respectively. Monoculus or binoculus disease, sleep status, health status, and depression /anxiety had statistically significant effects on the parental hope level (p < 0.05). Multiple linear regression analysis revealed that time since diagnosis, education level, treatment type and depression were independent influencing factors (p < 0.05), accounting for 22.60% of the variation in hope level. CONCLUSION: During the COVID-19 pandemic, medical staff should formulate targeted intervention measures according to different characteristics of ocular disease, time since diagnosis, treatment type, parental educational level and emotional state in order to improve the level of parental hope.
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COVID-19 , Neoplasias de la Retina , Retinoblastoma , Ansiedad/epidemiología , Niño , China , Estudios Transversales , Depresión/epidemiología , Humanos , Pandemias , Padres , Retinoblastoma/epidemiología , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
Findings for the roles of dairy products, Ca and vitamin D on ovarian cancer risk remain controversial. We aimed to assess these associations by using an updated meta-analysis. Five electronic databases (e.g. PubMed and Embase) were searched from inception to 24 December 2019. Pooled relative risks (RR) with 95 % CI were calculated. A total of twenty-nine case-control or cohort studies were included. For comparisons of the highest v. lowest intakes, higher whole milk intake was associated with increased ovarian cancer risk (RR 1·35; 95 % CI 1·15, 1·59), whereas decreased risks were observed for higher intakes of low-fat milk (RR 0·84; 95 % CI 0·73, 0·96), dietary Ca (RR 0·71; 95 % CI 0·60, 0·84) and dietary vitamin D (RR 0·80; 95 % CI 0·67, 0·95). Additionally, for every 100 g/d increment, increased ovarian cancer risks were found for total dairy products (RR 1·03; 95 % CI 1·01, 1·04) and for whole milk (RR 1·07; 95 % CI 1·03, 1·11); however, decreased risks were found for 100 g/d increased intakes of low-fat milk (RR 0·95; 95 % CI 0·91, 0·99), cheese (RR 0·87; 95 % CI 0·76, 0·98), dietary Ca (RR 0·96; 95 % CI 0·95, 0·98), total Ca (RR 0·98; 95 % CI 0·97, 0·99), dietary vitamin D (RR 0·92; 95 % CI 0·87, 0·97) and increased levels of circulating vitamin D (RR 0·84; 95 % CI 0·72, 0·97). These results show that whole milk intake might contribute to a higher ovarian cancer risk, whereas low-fat milk, dietary Ca and dietary vitamin D might reduce the risk.
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Calcio de la Dieta/administración & dosificación , Productos Lácteos , Dieta , Neoplasias Ováricas/epidemiología , Vitamina D/administración & dosificación , Animales , Calcio/sangre , Estudios de Casos y Controles , Estudios de Cohortes , Productos Lácteos/efectos adversos , Dieta/efectos adversos , Femenino , Humanos , Leche/química , Riesgo , Vitamina D/sangreRESUMEN
BRAF and MEK inhibitors have shown remarkable clinical efficacy in BRAF-mutant melanoma; however, most patients develop resistance, which limits the clinical benefit of these agents. In this study, we found that the human melanoma cell clones, A375-DR and A375-TR, with acquired resistance to BRAF inhibitor dabrafenib and MEK inhibitor trametinib, were cross resistant to other MAPK pathway inhibitors. In these resistant cells, phosphorylation of ribosomal protein S6 (rpS6) but not phosphorylation of ERK or p90 ribosomal S6 kinase (RSK) were unable to be inhibited by MAPK pathway inhibitors. Notably, knockdown of rpS6 in these cells effectively downregulated G1 phase-related proteins, including RB, cyclin D1, and CDK6, induced cell cycle arrest, and inhibited proliferation, suggesting that aberrant modulation of rpS6 phosphorylation contributed to the acquired resistance. Interestingly, RSK inhibitor had little effect on rpS6 phosphorylation and cell proliferation in resistant cells, whereas P70S6K inhibitor showed stronger inhibitory effects on rpS6 phosphorylation and cell proliferation in resistant cells than in parental cells. Thus regulation of rpS6 phosphorylation, which is predominantly mediated by BRAF/MEK/ERK/RSK signaling in parental cells, was switched to mTOR/P70S6K signaling in resistant cells. Furthermore, mTOR inhibitors alone overcame acquired resistance and rescued the sensitivity of the resistant cells when combined with BRAF/MEK inhibitors. Taken together, our findings indicate that RSK-independent phosphorylation of rpS6 confers resistance to MAPK pathway inhibitors in BRAF-mutant melanoma, and that mTOR inhibitor-based regimens may provide alternative strategies to overcome this acquired resistance.
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Resistencia a Antineoplásicos/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Proteína S6 Ribosómica/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Línea Celular Tumoral , Humanos , Imidazoles/farmacología , Melanoma/tratamiento farmacológico , Melanoma/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Mutación , Oximas/farmacología , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Proteínas Proto-Oncogénicas B-raf/genética , Piridonas/farmacología , Pirimidinonas/farmacologíaRESUMEN
PURPOSE: The causes of anemia and the common side effects of cancer are multifactorial. Malnutrition is one of the alleged components of the aforementioned complications. This study planned to investigate the relationship among biochemical markers, Patient-Generated Subjective Global Assessment (PG-SGA), and anemia in cancer patients. METHODS: This analysis consisted of 234 patients who were enlisted in the Department of Oncology of the First Hospital of Shanxi Medical University between December 2016 and October 2017. The groups were divided into anemic and non-anemic patients. The gathered data primarily discussed the patients' basic information, specifically the age, gender, smoking, alcohol consumption, and nutritional status based on levels of serum biochemical markers and PG-SGA scores. RESULTS: Among the participants, 31.2% of the cancer patients were diagnosed with anemia whereas, according to the scores of PG.SGA, 65.0% of patients experienced malnourishment. The anemia was significantly associated with biochemical markers, expecting a transferrin in univariable analyses. Binary logistic regression analysis between anemic cancer patients and non-anemic cancer patients suggested that high PG-SGA score (odds ratio 1.082; 95% CI 1.027-1.141) implied the risk factor for anemia, and high PG-SGA scores could potentially increase the risk of anemia. The multiple regression analysis showed that hemoglobin concentration (OR 0.575; 95% CI 0.450-0.736) and PG-SGA score (OR 1.231; 95% CI 1.013-1.496) were linked to anemia. However, total protein, albumin, prealbumin, serum iron, transferrin, and transferrin saturation lacked a strong relationship with anemia. CONCLUSION: Anemia prevailed in cancer patients, as nutritionally assessed by PG-SGA, while hemoglobin established a linkage with anemia as they could provide extra predictive information about anemia in patients diagnosed with cancer.
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Anemia/diagnóstico , Biomarcadores/análisis , Neoplasias/diagnóstico , Evaluación Nutricional , Medición de Resultados Informados por el Paciente , Adulto , Anciano , Anemia/etiología , Estudios Transversales , Femenino , Humanos , Masculino , Desnutrición/diagnóstico , Desnutrición/epidemiología , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/epidemiología , Estado Nutricional , Pronóstico , Factores de RiesgoRESUMEN
OBJECTIVES: Gonorrhea remains a major public health concern worldwide. This study aims to explore the spatiotemporal distribution and sociodemographic determinants of gonorrhea rates during 2004-2014 in mainland China. STUDY DESIGN: Space-time scan statistics and spatial panel regression model. METHODS: The gonorrhea infection data and sociodemographic data during 2004-2014 at the provincial level in mainland China were extracted from the China Public Health Science Data Center and China Statistical Yearbooks, respectively. The space-time scan statistics were used to identify the high-risk clusters of gonorrhea, and the spatial panel regression model was adopted to examine the sociodemographic determinants. RESULTS: One most likely and five secondary high-risk clusters of gonorrhea rates were identified, which were mainly located in southern and eastern China. The regions with higher GDP per capita, larger floating population, less access to healthcare, higher male-female ratio, and higher divorce rate were more likely to become high-risk areas of gonorrhea. CONCLUSIONS: Gonorrhea rates were distributed unevenly through space and time and affected by various sociodemographic variables. The space-time scan statistics and spatial panel regression are viable tools for identifying clusters and examining determinants of gonorrhea rates. The findings provide valuable implications for developing targeted prevention and control programs in public health practice.
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Gonorrea/epidemiología , China/epidemiología , Análisis por Conglomerados , Femenino , Humanos , Masculino , Factores de Riesgo , Factores Socioeconómicos , Análisis Espacio-TemporalRESUMEN
Dairy goats serve as an important source of milk and also fulfill agricultural and economic roles in developing countries. Understanding the genetic background of goat mammary gland is important for research on the regulatory mechanisms controlling tissue function and the synthesis of milk components. We collected tissue at four different stages of goat mammary gland development and generated approximately 25 GB of data from Illumina de novo RNA sequencing. The combined reads were assembled into 51,361 unigenes, and approximately 60.07 % of the unigenes had homology to other proteins in the NCBI non-redundant protein database (NR). Functional classification through eukaryotic Ortholog Groups of Protein (KOG), gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the unigenes from goat mammary glands are involved in a wide range of biological processes and metabolic pathways, including lipid metabolism and lactose metabolism. The results of qPCR revealed that genes encoding FABP3, FASN, SCD, PLIN2, whey proteins (LALBA and BLG), and caseins (CSN1S1, CSN1S2, CSN2 and CSN3) at 100 and 310 days postpartum increased significantly compared with the non-lactating period. In addition to their role in lipid and protein synthesis, the higher expression at 310 days postpartum could contribute to mammary cell turnover during pregnancy. In conclusion, this is the first study to characterize the complete transcriptome of goat mammary glands and constitutes a comprehensive genomic resource available for further studies of ruminant lactation.
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Cabras/genética , Lactancia/genética , Metabolismo de los Lípidos/genética , Glándulas Mamarias Animales/metabolismo , Transcriptoma , Animales , Industria Lechera , Femenino , Perfilación de la Expresión Génica , Ontología de Genes , Cabras/metabolismo , Glándulas Mamarias Animales/enzimología , Redes y Vías Metabólicas/genética , Proteínas de la Leche/genética , Proteínas de la Leche/metabolismo , Anotación de Secuencia Molecular , Análisis de Secuencia de ARNRESUMEN
In order to mitigate the risk of excessive heavy metal intake, a study was conducted to assess the levels of arsenic (As), cadmium (Cd), chromium (Cr), and lead (Pb) contamination in 23 edible seafood species obtained from markets in Haikou. The findings were analyzed to evaluate the potential health hazards posed to the local population through consumption. The metals were detected via inductively coupled plasma mass spectrometry (ICP-MS) for quantification. The non-carcinogenic and carcinogenic health risks in humans were assessed via target hazard quotient (THQ), combined target hazard quotient (CTHQ), and target cancer risk (TR). The results indicated that the rank order based on the median metal concentration was As > Cd > Cr > Pb. THQ and CTHQ showed that nine seafood species posed a non-carcinogenic risk regarding from As and Cd consumption separately, or the four targeted metals ingestion together. TR assessment indicated that the InAs in all the species presented a carcinogenic risk to coastal residents. The Cd content in bivalves, algae, and several crustacean (Mantis Shrimp, Orchid Crab, Red spot Swimming Crab) and fish species (Japanese Scad, Pacific Saury), and Cr levels in most bivalve species (Razor Clams, White Clams, Fan Shells, Oysters, Blood Clams) presented a carcinogenic risk. The As, Cd, Pb, and Cr levels of seafood in Haikou were assessed species presented a potential health risk. Necessitating stricter risk should be management and detection capability and monitoring will be improved.
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Arsénico , Cadmio , Cromo , Contaminación de Alimentos , Plomo , Alimentos Marinos , Alimentos Marinos/análisis , Medición de Riesgo , Cadmio/análisis , Arsénico/análisis , Plomo/análisis , Animales , Humanos , Contaminación de Alimentos/análisis , Cromo/análisis , Metales Pesados/análisis , Contaminantes Químicos del Agua/análisis , ChinaRESUMEN
BACKGROUND: Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology. Alkaline sphingomyelinase (alk-SMase) is specifically expressed by intestinal epithelial cells, and has been reported to play an anti-inflammatory role. However, the underlying mechanism is still unclear. AIM: To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium (DSS)-induced colitis. METHODS: Mice were administered 3% DSS drinking water, and disease activity index was determined to evaluate the status of colitis. Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran, and bacterial translocation was evaluated by measuring serum lipopolysaccharide. Intestinal epithelial cell ultrastructure was observed by electron microscopy. Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA, respectively. Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels. RESULTS: Compared to wild-type (WT) mice, inflammation and intestinal permeability in alk-SMase knockout (KO) mice were more severe beginning 4 d after DSS induction. The mRNA and protein levels of intestinal barrier proteins, including zonula occludens-1, occludin, claudin-3, claudin-5, claudin-8, mucin 2, and secretory immunoglobulin A, were significantly reduced on 4 d after DSS treatment. Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells. Furthermore, by day 4, mitochondria appeared swollen and degenerated. Additionally, compared to WT mice, serum malondialdehyde levels in KO mice were higher, and the antioxidant capacity was significantly lower. The expression of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment. mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased. Finally, colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone, which is an Nrf2 activator. CONCLUSION: Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.
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Colitis Ulcerosa , Colitis , Enfermedad de Niemann-Pick Tipo A , Animales , Ratones , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Colitis/tratamiento farmacológico , Colitis Ulcerosa/tratamiento farmacológico , Colon , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Mucosa Intestinal , Ratones Endogámicos C57BL , Ratones Noqueados , Factor 2 Relacionado con NF-E2/metabolismo , Enfermedad de Niemann-Pick Tipo A/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , ARN Mensajero/metabolismoRESUMEN
OBJECTIVE: The aim of this study was to investigate the symptom and symptom clusters of patients with hepatocellular carcinoma (HCC) before and after transcatheter arterial chemoembolization (TACE), and to discuss the relationship between symptoms, symptom clusters, and symptom interference. MATERIALS AND METHODS: Patients with HCC who received TACE were asked to rate their symptoms using the M. D. Anderson Symptom Inventory and the symptom checklist particularly for HCC. To determine the interrelationships among symptoms and identify the symptom clusters, a principal component analysis with varimax rotation was carried out on the symptom items. Spearman correlation analysis was done to assess the relationship between symptom clusters and symptom interference. RESULTS: A total of 155 patients finished the whole procedure between November 2010 and May 2011. Before TACE, the five most severe symptoms, ranked in order, were fatigue (3.40 ± 2.26), distress (3.35 ± 2.60), sadness (3.01 ± 2.66), sleep disturbance (2.63 ± 2.57), and lack of appetite (2.26 ± 2.38). After TACE, fatigue (4.88 ± 2.31) was the most serious symptom, followed by sleep disturbance (4.80 ± 2.25), distress (4.59 ± 2.32), sadness (4.45 ± 2.16), lack of appetite (4.25 ± 2.51). Two symptom clusters were found before TACE: psychological symptom cluster and sickness symptom cluster. Two new symptom clusters were found after TACE: upper gastrointestinal symptom cluster and liver function impairment symptom cluster, with the two original symptom clusters remained relatively stable. The highest symptom interference items pre- and post-TACE were work and enjoyment of life, followed by mood. The symptoms of distress, sadness, fatigue, sleep disturbance, and lack of appetite were all significantly associated with the total interference (r = 0.443-0.615, p < 0.01 or p < 0.05). Symptom clusters were significantly correlated with the total symptom interference before and after TACE (r = 0.176-0.638, p < 0.01 or p < 0.05). CONCLUSION: Psychological symptom cluster and sickness symptom cluster are common for HCC patients before and after TACE. Liver function impairment and upper gastrointestinal symptom clusters are directly related to TACE treatment. Both the symptoms and symptom clusters have significant interference on the daily life of HCC patients undergoing TACE. However, more work is needed to further clarify the symptom clusters associated with TACE and to test the effectiveness of TACE in easing symptoms and improving quality of life of HCC patients.