RESUMEN
OBJECTIVE: Depression is a global health challenge, but only a few studies have fully assessed and predicted the disease burden. This study described the trend of global depression burden from 1990 to 2019 through age-standardized incidence rate (ASIR), age-standardized disability-adjusted life rate (ASDR), and predicted the number of cases of depression during 2020-2030. METHODS: Linear regression analysis was used to calculate the estimated annual percentage change (EAPC) in the age-standardized rates. The trends of global depression burden from 1990 to 2019 were analyzed by age, sex, and socio-demographic index (SDI) across various regions. Finally, we used the Bayesian age-period-cohort (BAPC) model to predict the disease burden in the coming 10 years. RESULTS: Globally, the ASIR of depression decreased from 3681.24 per 100,000 population in 1990 to 3588.25 per 100,000 population in 2019 and the EAPC was -0.29%. ASDR also decreased, following a similar trend as the ASIR. The highest ASDR was observed in adults aged 60-64 years. The burden of depressive illness was higher in women, with the greatest increase in incidence in low SDI areas. BAPC predicted that the worldwide ASIR and ASDR of depression would stabilize from 2020 to 2030, with an increasing number of cases. By 2030, the ASIR was estimated to be 2519.88 per 100,000 men and 3835.11 per 100,000 women. CONCLUSION: From 1990 to 2019, the global burden of depression remained significant, especially among women. It is important to address depression in older people, and it is therefore necessary to develop measures for prevention.
RESUMEN
The associations between blood benzene, toluene, ethylbenzene, and xylenes (BTEX) and biological aging among general adults remain elusive. The present study comprised 5780 participants from the National Health and Nutrition Examination Survey 1999-2010. A novel measure of biological aging, phenotypic age acceleration (PhenoAge.Accel), derived from biochemical markers was calculated. Weighted generalized linear regression and weighted quantile sum regression (WQS) were utilized to assess the associations between BTEX components and mixed exposure, and PhenoAge.Accel. The mediating roles of systemic immune-inflammation index (SII) and oxidative stress indicators (serum bilirubin and gamma-glutamyl transferase), along with the modifying effects of body mass index (BMI) were also examined. In the single-exposure model, the highest quantile of blood benzene (b = 0.89, 95%CI: 0.58 to 1.20), toluene (b = 0.87, 95%CI: 0.52 to 1.20), and ethylbenzene (b = 0.80, 95%CI: 0.46 to 1.10) was positively associated with PhenoAge.Accel compared to quantile 1. Mixed-exposure analyses revealed a consistent positive association between BTEX mixed exposure and PhenoAge.Accel (b = 0.88, 95%CI: 0.56 to 1.20), primarily driven by benzene (92.78%). The association between BTEX and PhenoAge.Accel was found to be partially mediated by inflammation and oxidative stress indicators (ranging from 3.2% to 13.7%). Additionally, BMI negatively modified the association between BTEX mixed exposure and PhenoAge.Accel, with a threshold identified at 36.2 kg/m^2. Furthermore, BMI negatively moderated the direct effect of BTEX mixed exposure on PhenoAge.Accel in moderated mediation models, while positively modified the link between SII and PhenoAge.Accel in the indirect path (binteraction = 0.04, 95%CI: 0.01 to 0.06). Overall, BTEX mixed exposure was associated with PhenoAge.Accel among US adults, with benzene may have reported most contribution, and inflammation and oxidative damage processes may partially explain this underlying mechanism. The study also highlighted the potential benefits of appropriate BMI increased. Additional large-scale cohort studies and experiments were necessary to substantiate these findings.
RESUMEN
OBJECTIVE: Genetic risks can accelerate ageing, yet better quality sleep may slow down it. We thus examined the interaction and combined effects of genetic predisposition and sleep quality on the risk of accelerate aging. METHODS: This study included 407,027 participants from the UK Biobank. Sleep index of each participant was retrieved from the following seven sleep behaviors: snoring, chronotype, daytime sleepiness, sleep duration, insomnia, nap and difficulties in getting up. The biological age (PhenoAge) were estimated by corresponding algorithms based on clinical traits, and their residual discrepancies with chronological age were defined as the age accelerations (PhenoAgeaccel). We explored the interaction and combined effects of genetic risk and sleep quality on accelerated ageing by constructing a linear model. RESULTS: Compared with participants in low sleep quality group, those in medium and high sleep quality group decreased 0.727 (95%CI, 0.653 to 0.801) and 1.056 (95%CI, 0.982 to 1.130) years of PhenoAgeaccel, respectively. Compared with participants in low genetic risk group, those in medium and high genetic risk group increased 0.833 (95%CI, 0.792 to 0.874) and 1.543 (95%CI, 1.494 to 1.592) years of PhenoAgeaccel, respectively. There was interaction between the genetic risk and sleep quality (P-interaction<0.001). For combined effect, compared to the group with high sleep quality and lower genetic risk, people with low sleep quality and high genetic risk had 2.747 (95%CI, 2.602 to 2.892) years higher PhenoAgeaccel. CONCLUSION: Our findings elucidate that better sleep quality could lessen accelerated biological ageing especially among population with high genetic risk.
RESUMEN
BACKGROUND: Carcass traits are essential economic traits in the commercial pig industry. However, the genetic mechanism of carcass traits is still unclear. In this study, we performed a genome-wide association study (GWAS) based on the specific-locus amplified fragment sequencing (SLAF-seq) to study seven carcass traits on 223 four-way intercross pigs, including dressing percentage (DP), number of ribs (RIB), skin thinkness (ST), carcass straight length (CSL), carcass diagonal length (CDL), loin eye width (LEW), and loin eye thickness (LET). RESULTS: A total of 227,921 high-quality single nucleotide polymorphisms (SNPs) were detected to perform GWAS. A total of 30 SNPs were identified for seven carcass traits using the mixed linear model (MLM) (p < 1.0 × 10- 5), of which 9 SNPs were located in previously reported quantitative trait loci (QTL) regions. The phenotypic variation explained (PVE) by the significant SNPs was from 2.43 to 16.32%. Furthermore, 11 candidate genes (LYPLAL1, EPC1, MATN2, ZFAT, ZBTB10, ZNF704, INHBA, SMYD3, PAK1, SPTBN2, and ACTN3) were found for carcass traits in pigs. CONCLUSIONS: The GWAS results will improve our understanding of the genetic basis of carcass traits. We hypothesized that the candidate genes associated with these discovered SNPs would offer a biological basis for enhancing the carcass quality of pigs in swine breeding.
Asunto(s)
Estudio de Asociación del Genoma Completo , Fenotipo , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Animales , Porcinos/genética , Cruzamientos Genéticos , CarneRESUMEN
PURPOSE: Valbenazine is commonly used to treat tardive dyskinesia, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) to evaluate neurological safety signals associated with valbenazine. METHODS: Data was collected in FAERS from the second quarter of 2017 to the fourth quarter of 2023 for data cleaning. Neurological adverse event (AE) signals of valbenazine were mined by calculating reporting odds ratios (ROR), information component (IC) and empirical Bayesian geometric mean (EBGM). The serious and non-serious cases and signals were prioritized using a rating scale. RESULTS: The number of neurological AE reports where the primary suspect (PS) drug was 8981 for valbenazine. Significant AE signals were identified by the preferred term (PT) analysis for valbenazine, including somnolence (ROR 19.69), tremor (ROR 15.17), and tardive dyskinesia (ROR 236.91), among which 18 AEs were identified as new signals. Patient age (p < 0.009) and sex (p = 0.197) might be associated with an increased risk of neurological AE severity. Notably, the association between valbenazine and neurological disorders remained when stratified by sex, age, and reporter type. AE timing analysis was performed for the drug and four moderate clinical priority signals [i.e., somnolence, balance disorder, parkinsonism, and akathisia (priorities 7)], showing the same early failure type profiles. CONCLUSIONS: The increase in neurological safety signals is identified in the post-marketing research of valbenazine. Clinicians need to pay attention to not only common AEs but also be alert to new neurological AE signals when using valbenazine.
RESUMEN
PURPOSE: No study has comprehensively assessed the relationship of metabolic factors including insulin resistance, hypertension, hyperuricemia, and hypercholesterolemia with the development of carotid plaque. Therefore, we constructed metabolic scores based on the above metabolic factors and examined its association with carotid plaque in young and older Chinese adults. METHODS: This study included 17,396 participants who underwent carotid ultrasound examinations, including 14,173 young adults (<65 years) and 3,223 older adults (≥65 years). Individual metabolic score was calculated using triglyceride-glucose (TyG) index, mean arterial pressure (MAP), uric acid, and total cholesterol (TC). Logistic regression models were conducted to examine the role of metabolic score and its components in the prevalence of carotid plaque. The nonlinear relationship was examined using restricted cubic spline regression. Meanwhile, subgroup, interaction, and sensitivity analyses were conducted. RESULTS: The multivariate logistic regression analysis showed that TyG (OR: 1.088; 95%CI: 1.046-1.132), MAP (OR: 1.121; 95%CI: 1.077-1.168), TC (OR: 1.137; 95%CI: 1.094-1.182) and metabolic score (OR: 1.064; 95%CI: 1.046-1.082) were associated with carotid plaque prevalence in young adults rather than older adults. The nonlinear association was not observed for metabolic scores and carotid plaque. Subgroup analyses showed significant associations between metabolic scores and carotid plaque prevalence in men, women, normal-weight, and overweight young adults. No interaction of metabolic score with sex and BMI were observed. CONCLUSIONS: The results support that control of TyG, MAP, TC, and metabolic scores is a key point in preventing the prevalence of carotid plaque in the young adults.
RESUMEN
Abdominal subcutaneous fat deposition (ASFD) is not only related to meat quality in the pig industry but also to human health in medicine. It is of great value to elucidate the potential molecular mechanisms of ASFD. The present study aims to identify obese-specific biomarkers and key pathways correlated with ASFD in pigs. The ASF-related mRNA expression dataset GSE136754 was retrieved from the Gene Expression Omnibus (GEO) database and systematically analyzed using a comprehensive bioinformatics method. A total of 565 differentially expressed genes (DEGs) were identified between three obese and three lean pigs, and these DEGs were mainly involved in the p53 signaling pathway, MAPK signaling pathway and fatty acid metabolism. A protein-protein interaction (PPI) network, consisting of 540 nodes and 1,065 edges, was constructed, and the top ten genes with the highest degree scores-ABL1, HDAC1, CDC42, HDAC2, MRPS5, MRPS10, MDM2, JUP, RPL7L1 and UQCRFS1-were identified as hub genes in the whole PPI network. Especially HDAC1, MDM2, MRPS10 and RPL7L1 were identified as potential robust obese-specific biomarkers due to their significant differences in single gene expression levels and high ROC area; this was further verified by quantitative real-time PCR (qRT-PCR) on abdominal subcutaneous fat samples from obese-type (Saba) and lean-type (Large White) pigs. Additionally, a mRNA-miRNA-lncRNA ceRNA network consisting of four potential biomarkers, 15 miRNAs and 51 lncRNAs was established, and two targeted lncRNAs with more connections, XIST and NEAT1, were identified as potentially important regulatory factors. The findings of this study may provide novel insights into the molecular mechanism involved in ASFD.
Asunto(s)
Biomarcadores , Biología Computacional , Obesidad , Grasa Subcutánea Abdominal , Animales , Obesidad/genética , Obesidad/metabolismo , Biología Computacional/métodos , Porcinos , Biomarcadores/metabolismo , Grasa Subcutánea Abdominal/metabolismo , Mapas de Interacción de Proteínas , Perfilación de la Expresión Génica , Transducción de Señal/genética , Redes Reguladoras de GenesRESUMEN
BACKGROUND: High dietary diversity has been found to be associated with frailty. However, the trajectory of dietary diversity intake in relation to frailty is unclear. METHODS: Using the latent class trajectory modeling approach, we identified distinctive dietary variety trajectory groups among 2017 participants based on the Chinese Longitudinal Healthy Longevity Survey acquired at four time points within a 10-year period. Frailty status was assessed using a frailty index comprising 37 health deficits. Dietary diversity was quantified using the dietary variety score (DVS), based on food category consumption frequency. Logistic regression analyses were employed to explore the association between DVS change trajectories and frailty. RESULTS: This study identified two distinct DVS trajectories: "Moderate-Slow decline-Slow growth", encompassing 810 (40.16%) individuals, and "Moderate-Slow growth-Accelerated decline", including 1207 (59.84%) individuals. After adjusting for covariates, the odds ratio for DVS in the "Moderate-Slow decline-Slow growth" group was 1.326 (95% confidence interval: 1.075-1.636) compared to the "Moderate-Slow growth-Accelerated decline" group. The "Moderate-Slow decline-Slow growth" trajectory continued to decrease and was maintained at a low level in the early stages of aging. CONCLUSION: Sustaining a high dietary diversity trajectory over time, particularly in the early stages of aging, could potentially decrease the risk of frailty among older Chinese adults.
Asunto(s)
Dieta , Anciano Frágil , Fragilidad , Análisis de Clases Latentes , Humanos , Anciano , Femenino , Masculino , China/epidemiología , Dieta/estadística & datos numéricos , Estudios Longitudinales , Anciano Frágil/estadística & datos numéricos , Anciano de 80 o más Años , Estudios de Cohortes , Pueblo Asiatico , Evaluación Geriátrica/métodos , Pueblos del Este de AsiaRESUMEN
Backfat thickness (BT) and intramuscular fat (IMF) content are closely appertained to meat production and quality in pig production. Deposition in subcutaneous adipose (SA) and IMF concerns different genes and regulatory mechanisms. And larger studies with rigorous design should be carried to explore the molecular regulation of fat deposition in different tissues. The purpose of this study is to gain a better understanding of the molecular mechanisms underlying differences in fat deposition among different tissues and identify tissue-specific genes involved in regulating fat deposition. The SA-associated datasets (GSE122349 and GSE145956) and IMF-associated datasets (GSE165613 and GSE207279) were downloaded from the Gene Expression Omnibus (GEO) as the BT and IMF group, respectively. Subsequently, the Robust Rank Aggregation (RRA) algorithm identified 27 down- and 29 up-regulated differentially expressed genes (DEGs) in the BT group. Based on bioinformatics and three machine learning algorithms, four SA deposition-related potential biomarkers, namely ACLY, FASN, ME1, and ARVCF were selected. FASN was evaluated as the most valuable biomarker for the SA mechanism. The 18 down- and 34 up-regulated DEGs in the IMF group were identified, and ACTA2 and HMGCL were screened as the IMF deposition-related candidate core genes, especially the ACTA2 may play the critical role in IMF deposition regulation. Moreover, based on the constructed ceRNA network, we postulated that the role of predicted ceRNA interaction network of XIST, NEAT1/miR-15a-5p, miR-16-5p, miR-424-5p, miR-497-5p/FASN were vital in the SA metabolism, XIST, NEAT1/miR-27a/b-3p, 181a/c-5p/ACTA2 might contribute to the regulation to IMF metabolism, which all gave suggestions in molecular mechanism for regulation of fat deposition. These findings may facilitate advancements in porcine quality at the genetic and molecular levels and assist with human obesity-associated diseases.
RESUMEN
Purpose: To assess the impact of maternal pre-pregnancy body mass index (BMI) on longitudinal fetal growth, and the potential mediation effect of the maternal fasting plasma glucose in first trimester. Methods: In this retrospective cohort study, we collected pre-pregnancy BMI data and ultrasound measurements during pregnancy of 3879 singleton pregnant women who underwent antenatal examinations and delivered at Peking Union Medical College Hospital. Generalized estimation equations, linear regression, and logistic regression were used to examine the association between pre-pregnancy BMI with fetal growth and adverse neonatal outcomes. Mediation analyses were also used to examine the mediating role of maternal fasting plasma glucose (FPG) in first trimester. Results: A per 1 Kg/m² increase in pre-pregnancy BMI was associated with increase fetal body length Z-score (ß 0.010, 95% CI 0.001, 0.019) and fetal body weight (ß 0.017, 95% CI 0.008, 0.027). In mid pregnancy, pre-pregnancy BMI also correlated with an increase Z-score of fetal abdominal circumference, femur length (FL). Pre-pregnancy BMI was associated with an increased risk of large for gestational age and macrosomia. Mediation analysis indicated that the associations between pre-pregnancy BMI and fetal weight in mid and late pregnancy, and at birth were partially mediated by maternal FPG in first trimester (mediation proportion: 5.0%, 8.3%, 1.6%, respectively). Conclusion: Maternal pre-pregnancy BMI was associated with the longitudinal fetal growth, and the association was partly driven by maternal FPG in first trimester. The study emphasized the importance of identifying and managing mothers with higher pre-pregnancy BMI to prevent fetal overgrowth.
RESUMEN
BACKGROUND: Non-invasive imaging methods are still lacking for evaluating bone changes in chronic kidney diseases (CKD). PURPOSE: To investigate the feasibility of chest CT radiomics in evaluating bone changes caused by CKD. MATERIAL AND METHODS: In total, 75 patients with stage 1 CKD (CKD1) and 75 with stage 5 CKD (CKD5) were assessed using the chest CT radiomics method. Radiomics features of bone were obtained using 3D Slicer software and were then compared between CKD1 and CKD5 cases. The methods of maximum correlation minimum redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) were used to establish a prediction model to determine CKD. The receiver operating characteristic (ROC) curve was used to determine the performance of the model. RESULTS: Cases of CKD1 and CKD5 differed in 40 radiomics features (P <0.05). Using the mRMR and LASSO methods, five features were finally selected to establish a predication model. The area under the receiver operating characteristic curve of the model in the determination of CKD1 and CKD5 was 0.903 and 0.854, respectively, for the training and validation cohorts. CONCLUSION: Chest CT radiomics is feasible in evaluating bone changes caused by CKD.
Asunto(s)
Estudios de Factibilidad , Insuficiencia Renal Crónica , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Insuficiencia Renal Crónica/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Anciano , Radiografía Torácica/métodos , Adulto , Estudios Retrospectivos , Huesos/diagnóstico por imagen , RadiómicaRESUMEN
Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates. Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity. This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes. The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes, and corresponding reference ranges will be established. The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance, with altitude gradients divided into 4 categories: 800 m, 1 900 m, 2 400 m, and 3 500 m, with an anticipated sample size of 170 neonates per altitude gradient. This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.
Asunto(s)
Altitud , Encéfalo , Electroencefalografía , Oxígeno , Humanos , Recién Nacido , Encéfalo/metabolismo , Oxígeno/metabolismo , Espectroscopía Infrarroja Corta , Estudios ProspectivosRESUMEN
Apigenin 7-glucoside (A7G) can suppress cell proliferation and trigger apoptosis in cervical cancer cells. Considering that hypoxia is associated with the malignant phenotypes in cervical cancer, this study aimed to uncover whether A7G exhibits suppressive effects on the hypoxia-induced malignant phenotype of cervical cancer cells (HeLa cells). Compared to normoxia, hypoxia can enhance the malignant phenotypes of HeLa cells, including cell proliferation, reduced sensitivity against chemotherapeutic agents (oxaliplatin and paclitaxel), cancer stemness, migration, and invasion. A7G intervention (20, 40, and 60 µM) could impair these malignant phenotypes of HeLa cells and upregulate the expression level of total and nuclear p16 proteins. Molecular docking analysis showed the interaction between anion exchanger 1 and A7G. In p16-silencing HeLa cells, the anticancer effects of A7G were absent. Therefore, hypoxia derives malignant phenotypes of HeLa cells, which could be impeded by A7G in a p16-dependent manner.
RESUMEN
High heritability and strong correlation have been observed in breast and ovarian cancers. However, their shared genetic architecture remained unclear. Linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics (ρ-HESS) were applied to estimate heritability and genetic correlations. Bivariate causal mixture model (MiXeR) was used to qualify the polygenic overlap. Then, stratified-LDSC (S-LDSC) was used to identify tissue and cell type specificity. Meanwhile, the adaptive association test called MTaSPUsSet was performed to identify potential pleiotropic genes. The Single Nucleotide Polymorphisms (SNP) heritability was 13% for breast cancer and 5% for ovarian cancer. There was a significant genetic correlation between breast and ovarian cancers (rg=0.21). Breast and ovarian cancers exhibited polygenic overlap, sharing 0.4 K out 2.8 K of causal variants. Tissue and cell type specificity displayed significant enrichment in female breast mammary, uterus, kidney tissues, and adipose cell. Moreover, the 74 potential pleiotropic genes were identified between breast and ovarian cancers, which were related to the regulation of cell cycle and cell death. We quantified the shared genetic architecture between breast and ovarian cancers and shed light on the biological basis of the co-morbidity. Ultimately, these findings facilitated the understanding of disease etiology.
RESUMEN
PURPOSE: Previous observational studies have suggested an association between sleep disturbance and metabolic syndrome (MetS). However, it remains unclear whether this association is causal. This study aims to investigate the causal effects of sleep-related traits on MetS using Mendelian randomization (MR). METHODS: Single-nucleotide polymorphisms strongly associated with daytime napping, insomnia, chronotype, short sleep, and long sleep were selected as genetic instruments from the corresponding genome-wide association studies (GWAS). Summary-level data for MetS were obtained from two independent GWAS datasets. Univariable and multivariable MR analyses were conducted to investigate and verify the causal effects of sleep traits on MetS. RESULTS: The univariable MR analysis demonstrated that genetically predicted daytime napping and insomnia were associated with increased risk of MetS in both discovery dataset (OR daytime napping = 1.630, 95% CI 1.273, 2.086; OR insomnia = 1.155, 95% CI 1.108, 1.204) and replication dataset (OR daytime napping = 1.325, 95% CI 1.131, 1.551; OR insomnia = 1.072, 95% CI 1.046, 1.099). For components, daytime napping was positively associated with triglycerides (beta = 0.383, 95% CI 0.160, 0.607) and waist circumference (beta = 0.383, 95% CI 0.184, 0.583). Insomnia was positively associated with hypertension (OR = 1.101, 95% CI 1.042, 1.162) and waist circumference (beta = 0.067, 95% CI 0.031, 0.104). The multivariable MR analysis indicated that the adverse effect of daytime napping and insomnia on MetS persisted after adjusting for BMI, smoking, drinking, and another sleep trait. CONCLUSION: Our study supported daytime napping and insomnia were potential causal factors for MetS characterized by central obesity, hypertension, or elevated triglycerides.
Asunto(s)
Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Síndrome Metabólico , Polimorfismo de Nucleótido Simple , Humanos , Síndrome Metabólico/genética , Síndrome Metabólico/epidemiología , Polimorfismo de Nucleótido Simple/genética , Sueño/genética , Sueño/fisiología , Trastornos del Inicio y del Mantenimiento del Sueño/genética , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Masculino , Trastornos del Sueño-Vigilia/genética , Trastornos del Sueño-Vigilia/epidemiología , FemeninoRESUMEN
BACKGROUND: Previous observational studies have suggested the association between rheumatoid arthritis (RA) and frailty. However, it remains obscure whether this association is causal. This study aims to investigate the causal association of RA with frailty and the mediation effect of inflammatory cytokines using Mendelian randomization (MR) design. METHODS: Summary-level data for RA (N = 58,284), frailty index (FI) (N = 175,226), Fried frailty score (FFS) (N = 386,565), and 41 inflammatory cytokines (N = 8,293) were obtained from recent genome-wide association studies. Univariable and multivariable MR analyses were conducted to investigate and verify the causal association of RA with frailty. The potential mediation effects of inflammatory cytokines were estimated using two-step MR. RESULTS: Univariable inverse variance weighted MR analysis suggested that genetically determined RA was associated with increased FI (beta=0.021; 95 % CI: 0.012, 0.03; p = 2.2 × 10-6) and FFS (beta=0.011; 95 %CI: 0.007, 0.015; p = 8.811 × 10-8). The consistent results were observed in multivariable MR analysis after adjustment for asthma, smoking, BMI, physical activity, telomere length, and depression. Mediation analysis showed evidence of an indirect effect of RA on FI through monokine induced by interferon-gamma (MIG) with a mediated proportion of 9.8 % (95 %CI: 4.76 %, 19.05 %), on FFS via MIG and stromal cell-derived factor-1 alpha with a mediated proportion of 9.6 % (95 %CI: 0 %, 18.18 %) and 8.44 % (95 %CI: 0 %, 18.18 %), respectively. CONCLUSION: This study provided credible evidence that genetically predicted RA was associated with a higher risk of frailty. Additionally, inflammatory cytokines were involved in the mechanism of RA-induced frailty.
Asunto(s)
Artritis Reumatoide , Citocinas , Fragilidad , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , Artritis Reumatoide/genética , Artritis Reumatoide/complicaciones , Fragilidad/genética , Citocinas/sangre , Citocinas/genética , Anciano , Masculino , Femenino , Análisis de Mediación , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
Bacterial drug resistance monitoring in hospitals is a crucial aspect of healthcare management and a growing concern worldwide. In this study, we analysed the bacterial drug resistance surveillance in our hospital from 2022 Q1 to 2023 Q2. The main sampling sources were respiratory, blood, and urine-based, and the main clinical infections were respiratory and genitourinary in nature. Specimens were inoculated and cultured; bacterial strains were isolated using a VITEK® 2 Compact 60-card automatic microorganism identifier (bioMerieux, Paris, France) and their matching identification cards were identified, and manual tests were supplemented for strain identification. The most common Gram-positive bacteria detected were Staphylococcus aureus, followed by Enterococcus faecalis (E. faecalis), Staphylococcus epidermidis (S. epidermidis), and Staphylococcus haemolyticus (S. haemolyticus). The most common Gram-negative bacteria detected were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The most prevalent multidrug-resistant bacteria were those producing extended-spectrum beta-lactamases, followed by methicillin-resistant Staphylococcus aureus, followed by carbapenem-resistant Enterobacterales. This study suggests that the prevention and control of infections in the respiratory and genitourinary systems should be the focus of anti-infective work and that the use of antimicrobials should be reduced and regulated to prevent the emergence and spread of resistant bacteria.
Asunto(s)
Antibacterianos , Staphylococcus aureus Resistente a Meticilina , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Departamentos de Hospitales , China/epidemiología , Escherichia coliRESUMEN
BACKGROUND: Despite some progress in pneumococcal immunization, the global burden of pneumococcal infection remains high, and pneumococcal disease remains a public health concern. Studies in China and abroad have found that 23-valent pneumococcal polysaccharide vaccine (PPV23) vaccination can effectively prevent invasive pneumococcal disease. This phase â clinical study assessed the safety and immunogenicity of a PPV23 vaccine candidate. METHODS: All subjects were randomly assigned to receive one dose intramuscular injection of experimental vaccine or control vaccine at a ratio of 1:1. The incidence of any adverse events was observed within 30 min, 0-7 days and 8-28 days post vaccination and the incidence of abnormal blood biochemical and blood routine indicators were tested on the 4th day post vaccination, the incidence of serious adverse events (SAEs) at 6 months post vaccination was recorded. Blood samples were collected prior to vaccination and on the 28th day post vaccination, and serum antibodies were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: The most common adverse reaction was pain at the injection site, followed by erythema. There was no significant difference of the incidence of systemic adverse reactions between the two vaccine groups. The adverse reactions observed in the trial were all common vaccination-related reactions, and no serious adverse reactions were observed. Compared to pre-vaccination, the (geometric mean concentrations) GMCs of IgG (immunoglobulin G) specific antibody against each serotype were all increased in the experimental group and the control group, there were statistical differences in seroconversion rates of serotypes 4 and 20 between the two vaccine groups. CONCLUSION: This clinical study showed good safety of the PPV23 vaccine candidate produced by Ab&b Biotechnology Co., Ltd.JS had good safety after vaccination in people aged 2 years and older. At the same time, good immunogenicity was also demonstrated.
Asunto(s)
Anticuerpos Antibacterianos , Infecciones Neumocócicas , Humanos , Vacunas Neumococicas , Infecciones Neumocócicas/prevención & control , Vacunación , Inmunoglobulina G , Inmunogenicidad Vacunal , Vacunas ConjugadasRESUMEN
BACKGROUND: Therapeutic drug monitoring (TDM) of antidepressants is essential for monitoring patient medication to avoid drug toxicity, complications, or nonadherence. Chromatographic techniques with high sensitivity and reproducibility are the main detection method for antidepressants. Effective pretreatment of biological sample processes is necessary prior to instrumental analysis. Magnetic solid-phase extraction (MSPE) has received much attention for its advantages of simple operation, rapidity, cost-effectiveness and low organic solvent consumption. Therefore, the development of a suitable and green magnetic sorbent for the detection of antidepressants in plasma and urine is apparently necessary. (88) RESULTS: A magnetic phytic acid-modified kapok fiber biochar sorbent (Fe3O4/PAKFBC) was successfully synthesized by pyrolytic impregnation and physical milling methods. Fe3O4/PAKFBC exhibited a large specific surface area (214 m2 g-1) and a rich pore structure (5-10 nm). The extraction equilibrium, using 10 mg Fe3O4/PAKFBC, can be completed in about 1 min. The density functional theory (DFT) results showed that the adsorption mechanism of Fe3O4/PAKFBC on the six antidepressants mainly included electrostatic interactions, van der Waals interactions, π-π interactions and weak hydrogen bonding. Examination using the greenness assessment tools showed that the developed method exhibited excellent greenness. By combining with liquid chromatography-ultraviolet (LC-UV), a quantitative method with good linearity (R2 > 0.993) and relative recoveries (92.4-107.7%) and negligible matrix effect (-11.5-6.0%) was developed. The Fe3O4/PAKFBC successfully detected six antidepressants in plasma and urine samples, requiring no pH adjustment with buffer salts. (142) SIGNIFICANCE: The environmental sustainability of the proposed methods was affirmed by six greenness evaluation tools, all indicating exceptional eco-friendliness. The Fe3O4/PAKFBC demonstrated outstanding greenness in both its creation and analytical application, proving highly effective in real sample applications and showcasing potential for broader use. This study contributes to a deeper and broader understanding of the microscopic adsorption mechanism, which can help in the optimization and development of more green sorbents. (69).
Asunto(s)
Antidepresivos , Carbón Orgánico , Ácido Fítico , Humanos , Reproducibilidad de los Resultados , Extracción en Fase Sólida/métodos , Fenómenos MagnéticosRESUMEN
BACKGROUND: Studies about the influence of weekday of esophagectomy on survival are limited and show conflicting results. This study aimed to explore whether weekday of esophagectomy affects patient's survival outcomes. METHODS: Patients who underwent esophagectomy in a grade-A tertiary hospital from January 2015 to December 2016 were enrolled. The primary outcome was 5-year overall survival (OS). The secondary outcomes were 5-year disease-free survival (DFS) and days of hospitalization. The impact of weekday surgery on 5-year OS and DFS were evaluated with Cox regression, and impact on days of hospitalization was assessed using logistic regression. Propensity score matching (PSM) analysis was used to balance the confounding factors. RESULTS: A total of 1478 patients were included. The 5-year OS and DFS were 63.77% and 59.26% respectively. Multivariate analyses adjusted for covariables indicated that weekday was not significantly associated with OS (P = 0.076), nor days of hospitalization (P = 0.824), but it appeared to be associated with DFS (P = 0.044). Additionally, PSM analysis showed no significant effect of weekday on the 5-year OS, nor DFS and days of hospitalization. CONCLUSION: In patients diagnosed with squamous esophageal cancer, the survival outcome of patients was not influenced by weekday.