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1.
Front Public Health ; 12: 1434089, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38989120

RESUMEN

Background: Empathy, as one of the fundamental principles of nursing professionalism, plays a pivotal role in the formation and advancement of the nursing team. Nursing interns, as a reserve force within the nursing team, are of significant importance in terms of their ability to empathize. This quality is not only directly related to the degree of harmony in the nurse-patient relationship and the enhancement of patient satisfaction, but also plays a pivotal role in the promotion of the quality of nursing services to a new level. Aim: The objective of this study was to gain a deeper understanding of the current state of nursing interns' empathic abilities. To this end, we sought to examine empathic performance under different profile models and to identify the key factors influencing these profile models. Methods: The study utilized 444 nursing interns from 11 tertiary general hospitals in Inner Mongolia as research subjects. The study employed a number of research tools, including demographic characteristics, the Jefferson Scale of Empathy, and the Professional Quality of Life Scale. A latent profile model of nursing interns' empathy ability was analyzed using Mplus 8.3. The test of variability of intergroup variables was performed using the chi-square test. Finally, the influencing factors of each profile model were analyzed by unordered multi-categorical logistic regression analysis. Results: The overall level of empathy among nursing interns was found to be low, with 45% belonging to the humanistic care group, 43% exhibiting low empathy, and 12% demonstrating high empathy. The internship duration, empathy satisfaction, secondary traumatic stress, only child, place of birth, and satisfaction with nursing were identified as factors influencing the latent profiles of empathy in nursing interns (p < 0.05). Conclusion: There is considerable heterogeneity in nursing interns' ability to empathize. Consequently, nursing educators and administrators should direct greater attention to interns with lower empathy and develop targeted intervention strategies based on the influences of the different underlying profiles.


Asunto(s)
Empatía , Humanos , Estudios Transversales , Masculino , Femenino , Adulto , Estudiantes de Enfermería/psicología , Estudiantes de Enfermería/estadística & datos numéricos , Relaciones Enfermero-Paciente , Encuestas y Cuestionarios , China , Competencia Clínica
2.
Biomedicines ; 12(6)2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38927450

RESUMEN

Coronary artery disease (CAD) is a common comorbidity of type 2 diabetes mellitus (T2DM). However, the pathophysiology connecting these two phenotypes remains to be further understood. Combined analysis in multi-ethnic populations can help contribute to deepening our understanding of biological mechanisms caused by shared genetic loci. We applied genetic correlation analysis and then performed conditional and joint association analyses in Chinese, Japanese, and European populations to identify the genetic variants jointly associated with CAD and T2DM. Next, the associations between genes and the two traits were also explored. Finally, fine-mapping and functional enrichment analysis were employed to identify the potential causal variants and pathways. Genetic correlation results indicated significant genetic overlap between CAD and T2DM in the three populations. Over 10,000 shared signals were identified, and 587 were shared by East Asian and European populations. Fifty-six novel shared genes were found to have significant effects on both CAD and T2DM. Most loci were fine-mapped to plausible causal variant sets. Several similarities and differences of the involved genes in GO terms and KEGG pathways were revealed across East Asian and European populations. These findings highlight the importance of immunoregulation, neuroregulation, heart development, and the regulation of glucose metabolism in shared etiological mechanisms between CAD and T2DM.

3.
Heliyon ; 10(10): e31339, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38813151

RESUMEN

Lead-acid batteries are noted for simple maintenance, long lifespan, stable quality, and high reliability, widely used in the field of energy storage. However, during the use of lead-acid batteries, the negative electrode is prone to irreversible sulfation, failing to meet the requirements of new applications such as maintenance-free hybrid vehicles and solar energy storage. In this study, in order to overcome the sulfation problem and improve the cycle life of lead-acid batteries, active carbon (AC) was selected as a foaming agent and foam fixing agent, and carbon foams (CF) with layered porous structure was prepared by mixing with molten sucrose. Sucrose as raw material is green and cheap, and the material preparation process is simple. The prepared CF material was then added as an additive to the negative electrode plate, and the electrochemical performance of the electrode plate and the battery was studied. The results proved that the addition of CF could effectively inhibit the sulfate formation of the negative electrode plate, with the 1.0 % CF negative electrode plate showing the best electrochemical performance. Specifically, according to the result of battery cycle testing, the simulated battery with CF had a cycle life of 3642 times, which was 2.87 times that of the blank group and 2.39 times of the AC group. Meanwhile, rate testing showed that the simulated battery with CF could maintain a high capacity even under high-rate discharge conditions.

4.
Int J Mol Sci ; 25(7)2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38612691

RESUMEN

Plant annexins constitute a conserved protein family that plays crucial roles in regulating plant growth and development, as well as in responses to both biotic and abiotic stresses. In this study, a total of 144 annexin genes were identified in the barley pan-genome, comprising 12 reference genomes, including cultivated barley, landraces, and wild barley. Their chromosomal locations, physical-chemical characteristics, gene structures, conserved domains, and subcellular localizations were systematically analyzed to reveal the certain differences between wild and cultivated populations. Through a cis-acting element analysis, co-expression network, and large-scale transcriptome analysis, their involvement in growth, development, and responses to various stressors was highlighted. It is worth noting that HvMOREXann5 is only expressed in pistils and anthers, indicating its crucial role in reproductive development. Based on the resequencing data from 282 barley accessions worldwide, genetic variations in thefamily were investigated, and the results showed that 5 out of the 12 identified HvMOREXanns were affected by selection pressure. Genetic diversity and haplotype frequency showed notable reductions between wild and domesticated barley, suggesting that a genetic bottleneck occurred on the annexin family during the barley domestication process. Finally, qRT-PCR analysis confirmed the up-regulation of HvMOREXann7 under drought stress, along with significant differences between wild accessions and varieties. This study provides some insights into the genome organization and genetic characteristics of the annexin gene family in barley at the pan-genome level, which will contribute to better understanding its evolution and function in barley and other crops.


Asunto(s)
Hordeum , Procedimientos de Cirugía Plástica , Hordeum/genética , Anexinas/genética , Domesticación , Productos Agrícolas
5.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(1): 174-178, 2024 Feb 18.
Artículo en Chino | MEDLINE | ID: mdl-38318914

RESUMEN

OBJECTIVE: To explore the robust relationship between insomnia and type 2 diabetes mellitus by two-sample Mendelian randomization analysis to overcome confounding factors and reverse causality in observational studies. METHODS: We identified strong, independent single nucleotide polymorphisms (SNPs) of insomnia from the most up to date genome wide association studies (GWAS) within European ancestors and applied them as instrumental variable to GWAS of type 2 diabetes mellitus. After excluding SNPs that were significantly associated with smoking, physical activity, alcohol consumption, educational attainment, obesity, or type 2 diabetes mellitus, we assessed the impact of insomnia on type 2 diabetes mellitus using inverse variance weighting (IVW) method. Weighted median and MR-Egger regression analysis were also conducted to test the robustness of the association. We calculated the F statistic of the selected SNPs to test the applicability of instrumental variable and F statistic over than ten indicated that there was little possibility of bias of weak instrumental variables. We further examined the existence of pleiotropy by testing whether the intercept term in MR-Egger regression was significantly different from zero. In addition, the leave-one-out method was used for sensitivity analysis to verify the stability and reliability of the results. RESULTS: We selected 248 SNPs independently associated with insomnia at the genome-wide level (P<5×10-8) as a preliminary candidate set of instrumental variables. After clumping based on the reference panel from 1000 Genome Project and removing the potential pleiotropic SNPs, a total of 167 SNPs associated with insomnia were included as final instrumental variables. The F statistic of this study was 39. 74, which was in line with the relevance assumption of Mendelian randomization. IVW method showed insomnia was associated with higher risk of type 2 diabetes mellitus that po-pulation with insomnia were 1. 14 times more likely to develop type 2 diabetes mellitus than those without insomnia (95% CI: 1.09-1.21, P<0.001). The weighted median estimator (WME) method and MR-Egger regression showed similar causal effect of insomnia on type 2 diabetes mellitus. And MR-Egger regression also showed that the effect was less likely to be triggered by pleiotropy. Sensitivity analyses produced directionally similar estimates. CONCLUSION: Insomnia is a risk factor of type 2 diabetes mellitus, which has positively effects on type 2 diabetes mellitus. Our study provides further rationale for indivi-duals at risk for diabetes to keep healthy lifestyle.


Asunto(s)
Diabetes Mellitus Tipo 2 , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Trastornos del Inicio y del Mantenimiento del Sueño/genética , Estudio de Asociación del Genoma Completo , Reproducibilidad de los Resultados , Factores de Riesgo , Polimorfismo de Nucleótido Simple , Análisis de la Aleatorización Mendeliana
7.
Cardiovasc Intervent Radiol ; 46(10): 1394-1400, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37723354

RESUMEN

PURPOSE: This study aimed to assess the safety, effectiveness, and feasibility of the Liverty™ transjugular intrahepatic portosystemic shunt (TIPS) access set, which has an ergonomic handle that allows for in situ cannula tip deflection and a distal steerable cannula angle, versus the COOK® Rosch-Uchida Transjugular Liver Access Set (RUPS-100) in healthy pigs. METHODS: Twelve pigs randomly underwent TIPS with the Liverty™ set or the RUPS-100 set. Three interventionalists performed 4 TIPS procedures, 2 with each set. The primary outcome was procedural success, defined as successful establishment of the intrahepatic portosystemic shunt and stent placement. RESULTS: The shunt was successfully established in 11 pigs. The procedural success was achieved in all 6 pigs in the Liverty™ group and 5 out of 6 pigs for the RUPS-100 group (Fisher exact test, P > 0.999). The mean duration of puncture was shorter in the Liverty™ group versus the RUPS-100 group (12.3 ± 4.5 min vs. 16.2 ± 8.5 min), but without significant statistical difference (two sample t test, P = 0.359). The cannula angle was adjusted 69% of passes in the Liverty™ group, which was significantly higher than that in the RUPS-100 group (12%, P = 0.004). Overall, the TIPS procedural performance was comparable between the groups. Both sets were safe. No intraabdominal hemorrhage, vascular injuries, tissue or organ injuries, porto-biliary fistula, biliary peritonitis, and infection or abscess occurred in either group. CONCLUSION: The Liverty™ set is safe and has similar procedural metrics to the COOK® RUPS-100 set. It allows in situ adjustment of the angle of the stiffening cannula without increasing procedure time and lessens the occurrences of periprocedural complications.


Asunto(s)
Derivación Portosistémica Intrahepática Transyugular , Animales , Porcinos , Derivación Portosistémica Intrahepática Transyugular/métodos , Cánula , Resultado del Tratamiento , Estudios Retrospectivos , Hígado , Vena Porta/cirugía
8.
Molecules ; 28(14)2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37513491

RESUMEN

The performance of lead-acid batteries could be significantly increased by incorporating carbon materials into the negative electrodes. In this study, a modified carbon material developed via a simple high-temperature calcination method was employed as a negative electrode additive, and we have named it as follows: N-doped chitosan-derived carbon (NCC). The performance of this material was compared with a control battery containing activated carbon (AC). X-ray diffraction (XRD), scanning electron microscopy (SEM) and Raman spectroscopy were engaged in analyzing the crystal structure and morphology of the material. Afterwards, the electrochemical and battery performance was examined through cyclic voltammetry (CV), linear voltammetry (LSV) and constant current charge-discharge testing. Markedly, the electrode plate containing 1 wt.% NCC indicates the highest specific capacity (106.48 F g-1) as compared to the control battery, which is 1.56 times higher than the AC electrode plate and 4.75 times higher than the blank electrode plate. The linear voltammetry shows that the hydrogen precipitation current density of the 1 wt.% NCC electrode plate is only -0.028 A cm-2, a much higher value than that of the AC electrode plate. In addition, the simulated battery containing 1 wt.% NCC has a cycle life of 4324 cycles, which is 2.36 times longer than that of the same amount of additive AC battery (1834 cycles) and 5.34 times longer than that of the blank battery (809 cycles). In summary, NCC carbon has the advantage of extending the life of lead-acid batteries, rendering it a promising candidate for lead-acid battery additives.

9.
Nurs Open ; 10(8): 5509-5520, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37099249

RESUMEN

AIMS: To examine the factors influencing compassion fatigue and compassion satisfaction in obstetrics and gynaecology nurses and to explore the combined results of multiple factors. DESIGN: An online cross-sectional study was conducted. REVIEW METHODS: Data were collected from 311 nurses using a convenience sampling method from January to February 2022. Stepwise multiple linear regression analysis and mediation tests were performed. RESULTS: Compassion fatigue in obstetrics and gynaecology nurses was in the moderate to high levels. Physical status, number of children, emotional labour, lack of professional efficacy, emotional exhaustion and the none-only-child can influence compassion fatigue; lack of professional efficacy, cynicism, social support, work experience, employment status and night shift were predictive of compassion satisfaction. Social support partially mediated between lack of professional efficacy and compassion fatigue/compassion satisfaction; emotional labour moderated in the mediated analysis model. CONCLUSION: Moderate to high levels of compassion fatigue was present in 75.88% of obstetrics and gynaecology nurses. Some factors affect compassion fatigue and compassion satisfaction. Thus, nursing managers should consider factors and construct a monitoring system to reduce compassion fatigue and improve compassion satisfaction. IMPLICATIONS FOR THE PROFESSION: The results will provide a theoretical basis for improving job satisfaction and the quality of care in obstetrics and gynaecology nurses. And this may raise concerns about the occupational health of obstetrics and gynaecology nurses in China. REPORTING METHOD: The study was reported according to the STROBE. PATIENT OR PUBLIC CONTRIBUTION: The nurses spent time filling out the questionnaires during the data collection phase and answered the questions sincerely. WHAT DOES THIS ARTICLE CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: Obstetrics and gynaecology nurses with 4-16 years of experience are prone to experience compassion fatigue. The effect of lack of professional efficacy on compassion fatigue and compassion satisfaction can be improved by social support. RELEVANCE TO CLINICAL PRACTICE: Reducing nurse compassion fatigue and improving compassion satisfaction are important for providing quality nursing care to obstetrics and gynaecology patients. In addition, clarifying the influencing factors of compassion fatigue and compassion satisfaction can improve nurses' work efficiency and job satisfaction, and provide theoretical guidance for managers to implement interventions.


Asunto(s)
Agotamiento Profesional , Desgaste por Empatía , Ginecología , Enfermeras y Enfermeros , Obstetricia , Humanos , Desgaste por Empatía/psicología , Empatía , Estudios Transversales , Satisfacción Personal , Satisfacción en el Trabajo
10.
Curr Med Sci ; 43(3): 551-559, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37115398

RESUMEN

OBJECTIVE: To compare survival outcomes between primary radical surgery and primary radiation in early cervical cancer. METHODS: Patient information was extracted from the Surveillance, Epidemiology, and Results database. Patients diagnosed with early cervical cancer of stage T1a, T1b, and T2a (American Joint Committee on Cancer, 7th edition) from 1998 to 2015 were included in this study after propensity score matching. Overall survival (OS) was analyzed using the Kaplan-Meier method. RESULTS: Among the 4964 patients included in the study, 1080 patients were identified as having positive lymph nodes (N1), and 3884 patients were identified as having negative lymph nodes (N0). Patients with primary surgery had significantly longer 5-year OS than those with primary radiotherapy in both the N1 group (P<0.001) and N0 group (P<0.001). In the subgroup analysis, similar results were found in patients with positive lymph nodes of stage T1a (100.0% vs. 61.1%), T1b (84.1% vs. 64.3%), and T2a (74.4% vs. 63.8%). In patients with T1b1 and T2a1, primary surgery resulted in longer OS than primary radiation, but not in patients with T1b2 and T2a2. In multivariate analysis, the primary treatment was identified as an independent prognostic factor in both N1 and N0 patients (HRN1=2.522, 95% CI=1.919-3.054, PN1<0.001; HRN0=1.895, 95% CI=1.689-2.126, PN0<0.001). CONCLUSION: In early cervical cancer stage T1a, T1b1, and T2a1, primary surgery may result in longer OS than primary radiation for patients with and without lymph node metastasis.


Asunto(s)
Ganglios Linfáticos , Neoplasias del Cuello Uterino , Femenino , Humanos , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Estadificación de Neoplasias , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/patología
11.
ACS Appl Mater Interfaces ; 15(12): 15203-15219, 2023 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-36917732

RESUMEN

Radiation-induced brain injury (RIBI) is a severe, irreversible, or even life-threatening cerebral complication of radiotherapy in patients with head and neck tumors, and there is no satisfying prevention and effective treatment available for these patients. Amifostine (AMF) is a well-known free radical scavenger with demonstrated effectiveness in preventing radiation-induced toxicity. However, the limited permeability of AMF across the blood-brain barrier (BBB) when administered intravenously reduces the effectiveness of AMF in preventing RIBI. Herein, we construct a nanoparticle (NP) platform for BBB delivery of AMF. AMF is conjugated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-n-[poly(ethylene glycol)]-hydroxy succinamide [DSPE-PEG-NHS, PEG M 2000], and the product is DSPE-PEG-AMF. Then, the nanoparticles (DAPP NPs) were formed by self-assembly of poly(lactic-co-glycolic acid) (PLGA), DSPE-PEG-AMF, and polysorbate 80 (PS 80). PEG shields the nanoparticles from blood clearance by the reticuloendothelial system and lengthens the drug circulation time. PS 80 is used to encapsulate nanoparticles for medication delivery to the brain. The results of our study showed that DAPP NPs were able to effectively penetrate the blood-brain barrier (BBB) in healthy C57BL/6 mice. Furthermore, in a well-established mouse model of X-knife-induced brain injury, treatment with DAPP NPs (corresponding to 250 mg/kg AMF) was found to significantly reduce the volume of brain necrosis compared to mice treated with AMF (250 mg/kg). Importantly, the use of DAPP NPs was also shown to significantly mitigate the effects of radiation-induced neuronal damage and glial activation. This work presents a convenient brain-targeted AMF delivery system to achieve effective radioprotection for the brain, providing a promising strategy with tremendous clinical translation potential.


Asunto(s)
Amifostina , Lesiones Encefálicas , Nanopartículas , Ratones , Animales , Barrera Hematoencefálica , Amifostina/farmacología , Ratones Endogámicos C57BL , Encéfalo , Polietilenglicoles/farmacología , Polisorbatos , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/prevención & control
12.
Mol Carcinog ; 62(4): 479-492, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36621979

RESUMEN

High grade serous ovarian carcinoma (HGSOC) is lethal with insidious onset, rapid progression, poor prognosis, and limited treatment options. Polycomb repressor complexes (PRC) 1 and 2 are intimately involved in progression of many types of cancer including HGSOC. Unlike the consistent constitution of PRC2, PRC1 consists of diverse components whose clinical significance in HGSOC are not entirely clear. Here, prognosis-associated PRC1 components were identified through data-mining. CBX2 promoted proliferation and reduced apoptosis of HGSOC cell lines OVCAR4, OVCAR3, and CAOV3. Complete loss of CBX2 by CRISPR-cas9 editing (CBX2KO ) destabilized genome stability with increased spontaneous chromosomal breaks and tendency to polyploidy accompanied by disrupted cell cycle especially stalled G2/M transition and caused severe cell death. Wnt/ß-catenin/LEF1/TCF7L1 was activated in surviving OVCAR4-CBX2KO clones to bypass the crisis caused by loss of CBX2. The relieve of TCF7L1 core-promoter region occupied by CBX2 might be one of the possible explanations to TCF7L1 increase in OVCAR4-CBX2KO clones. Subcutaneous tumor model further validated that depletion of CBX2 repressed HGSOC cell line derived tumor growth. High immunohistochemistry score of CBX2 in primary ovarian cancer tissue associated with advanced clinical stage (p = 0.033), poor overall survival (HR = 3.056, 95% CI: 1.024-9.123), and progression free survival (HR = 4.455, 95% CI: 1.513-13.118) in HGSOC. Overall, our results suggested that CBX2 was a promising prognostic factor and therapeutic target in HGSOC.


Asunto(s)
Neoplasias Ováricas , Femenino , Humanos , Neoplasias Ováricas/patología , Apoptosis/genética , Línea Celular Tumoral , Ciclo Celular , Inestabilidad Genómica , Complejo Represivo Polycomb 1/genética
13.
PeerJ ; 11: e14595, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36718446

RESUMEN

Background and Objective: Epidemiological studies report associations between coronavirus disease 2019 (COVID-19) and periodontitis; however, causality has not been proven. The aim of this study is to assess the associations between COVID-19 susceptibility and periodontitis with two-sample Mendelian randomization (MR) analyses. Methods: A two-sample summary MR analysis was performed using data for outcome and exposure from the OpenGWAS database on people of European descent. Periodontal complex traits (PCTs) were chosen as a proxy for the periodontitis phenotype. The causal association between PCT3 (Aggregatibacter actinomycetemcomitans), PCT5 (Porphyromonas gingivalis), and gingival crevicular fluid (GCF) interleukin-1ß (IL-1ß) and COVID-19 were considered. Genome-wide association study (GWAS) data with the two largest sample sizes were selected as COVID-19 outcomes (datasets ebi-a-GCST010776 and ebi-a-GCST010777). Single-nucleotide polymorphisms (SNPs) associated with PCT3, PCT5, and GCF IL-1ß at statistical significance at genome-wide level (P < 5 × 10-8) were identified as genetic instruments. We used two-sample summary MR methods and tested the existence of a pleiotropic effect with MR-Egger. Results: Inverse-variance weighted (IVW) estimates showed that there was a positive association between COVID-19 risk and periodontitis (ebi-a-GCST010776: odds ratio [OR] = 1.02 (95% confidence interval (CI), 1.00-1.05), P = 0.0171; ebi-a-GCST010777: OR = 1.03 (95% CI, 1.00-1.05), P = 0.0397). The weighted median also showed directionally similar estimates. Exploration of the causal associations between other PCTs and COVID-19 identified a slight effect of local inflammatory response (GCF IL-1ß) on COVID-19 risk across the two datasets (ebi-a-GCST010776: IVW OR = 1.02 (95% CI, [1.01-1.03]), P < 0.001; ebi-a-GCST010777: IVW OR = 1.03 (95% CI, [1.02-1.04]), P < 0.001). The intercepts of MR-Egger yielded no proof for significant directional pleiotropy for either dataset (ebi-a-GCST010776: P = 0.7660; ebi-a-GCST010777: P = 0.6017). Conclusions: The findings suggests that periodontitis and the higher GCF IL-1ß levels is causally related to increase susceptibility of COVID-19. However, given the limitations of our study, the well-designed randomized controlled trials are needed to confirm its findings, which may represent a new non-pharmaceutical intervention for preventing COVID-19.


Asunto(s)
COVID-19 , Periodontitis , Humanos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , COVID-19/epidemiología , Periodontitis/epidemiología , Causalidad
15.
Cardiovasc Diabetol ; 21(1): 276, 2022 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-36494812

RESUMEN

BACKGROUND: Coronary heart disease (CHD) and type 2 diabetes (T2D) are two complex diseases with complex interrelationships. However, the genetic architecture of the two diseases is often studied independently by the individual single-nucleotide polymorphism (SNP) approach. Here, we presented a genotypic-phenotypic framework for deciphering the genetic architecture underlying the disease patterns of CHD and T2D. METHOD: A data-driven SNP-set approach was performed in a genome-wide association study consisting of subpopulations with different disease patterns of CHD and T2D (comorbidity, CHD without T2D, T2D without CHD and all none). We applied nonsmooth nonnegative matrix factorization (nsNMF) clustering to generate SNP sets interacting the information of SNP and subject. Relationships between SNP sets and phenotype sets harboring different disease patterns were then assessed, and we further co-clustered the SNP sets into a genetic network to topologically elucidate the genetic architecture composed of SNP sets. RESULTS: We identified 23 non-identical SNP sets with significant association with CHD or T2D (SNP-set based association test, P < 3.70 × [Formula: see text]). Among them, disease patterns involving CHD and T2D were related to distinct SNP sets (Hypergeometric test, P < 2.17 × [Formula: see text]). Accordingly, numerous genes (e.g., KLKs, GRM8, SHANK2) and pathways (e.g., fatty acid metabolism) were diversely implicated in different subtypes and related pathophysiological processes. Finally, we showed that the genetic architecture for disease patterns of CHD and T2D was composed of disjoint genetic networks (heterogeneity), with common genes contributing to it (pleiotropy). CONCLUSION: The SNP-set approach deciphered the complexity of both genotype and phenotype as well as their complex relationships. Different disease patterns of CHD and T2D share distinct genetic architectures, for which lipid metabolism related to fibrosis may be an atherogenic pathway that is specifically activated by diabetes. Our findings provide new insights for exploring new biological pathways.


Asunto(s)
Enfermedad Coronaria , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Estudio de Asociación del Genoma Completo , Predisposición Genética a la Enfermedad , Redes Reguladoras de Genes , Polimorfismo de Nucleótido Simple , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/genética
16.
Front Endocrinol (Lausanne) ; 13: 1009095, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36465637

RESUMEN

Objective: Hyperlipidemia is traditionally considered a risk factor for diabetes. The effect of low-density lipoprotein cholesterol (LDL-C) is counterintuitive to diabetes. We sought to investigate the relationship between LDL-C and diabetes for better lipid management. Methods: We tested the shape of association between LDL-C and diabetes and created polygenic risk scores of LDL-C and generated linear Mendelian randomization (MR) estimates for the effect of LDL-C and diabetes. We evaluated for nonlinearity in the observational and genetic relationship between LDL-C and diabetes. Results: Traditional observational analysis suggested a complex non-linear association between LDL-C and diabetes while nonlinear MR analyses found no evidence for a non-linear association. Under the assumption of linear association, we found a consistently protective effect of LDL-C against diabetes among the females without lipid-lowering drugs use. The ORs were 0.84 (95% CI, 0.72-0.97, P=0.0168) in an observational analysis which was more prominent in MR analysis and suggested increasing the overall distribution of LDL-C in females led to an overall decrease in the risk of diabetes (P=0.0258). Conclusions: We verified the liner protective effect of LDL-C against diabetes among the females without lipid-lowering drug use. Non-linear associations between LDL-C against diabetes in observational analysis are not causal.


Asunto(s)
Diabetes Mellitus , Femenino , Humanos , LDL-Colesterol , Diabetes Mellitus/epidemiología , Diabetes Mellitus/genética , Análisis de la Aleatorización Mendeliana , Factores de Riesgo
17.
Biomedicines ; 10(12)2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36551856

RESUMEN

The aggregation and interaction of metabolic risk factors leads to highly heterogeneous pathogeneses, manifestations, and outcomes, hindering risk stratification and targeted management. To deconstruct the heterogeneity, we used baseline data from phase II of the Fangshan Family-Based Ischemic Stroke Study (FISSIC), and a total of 4632 participants were included. A total of 732 individuals who did not have any component of metabolic syndrome (MetS) were set as a reference group, while 3900 individuals with metabolic abnormalities were clustered into subtypes using multi-trait limited mixed regression (MFMR). Four metabolic subtypes were identified with the dominant characteristics of abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. Multivariate logistic regression showed that the hyperglycemia-dominant subtype had the highest coronary heart disease (CHD) risk (OR: 6.440, 95% CI: 3.177-13.977) and that the dyslipidemia-dominant subtype had the highest stroke risk (OR: 2.450, 95% CI: 1.250-5.265). Exome-wide association studies (EWASs) identified eight SNPs related to the dyslipidemia-dominant subtype with genome-wide significance, which were located in the genes APOA5, BUD13, ZNF259, and WNT4. Functional analysis revealed an enrichment of top genes in metabolism-related biological pathways and expression in the heart, brain, arteries, and kidneys. Our findings provide directions for future attempts at risk stratification and evidence-based management in populations with metabolic abnormalities from a systematic perspective.

18.
Expert Rev Vaccines ; 21(12): 1923-1928, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36328952

RESUMEN

BACKGROUND: Post-vaccination safety is a major public health concern. The genetic predisposition on immune response has not been clearly identified. Clarifying whether individual genetic predisposition plays a role on adverse events (AEs) is critical for the prevention of AEs. METHODS: From July 2019 to June 2020, we performed a case-control study among children aged 3-24 months in seven Chinese provinces. Each child received a combination vaccination against diphtheria, tetanus, acellular pertussis, and Haemophilus influenzae type b (DTaP-Hib). Through daily telephone follow-up, we collected AEs within seven days. Oral swab samples were collected to investigate the effects of single nucleotide polymorphisms (SNPs) on the risk of AEs. RESULTS: 304 participants were included in the study. In univariate analysis, we discovered three protective SNPs (rs452204, OR = 0.67, P = 0.0352; rs9282763 and rs839, OR = 0.64, P = 0.0256) and one risk SNP (rs9610, OR = 2.20, P = 0.0397). In multivariate analysis, the effects of rs452204 and rs839 were found to be stable. The interaction between rs452204 and rs9610 was observed (OR = 7.25, 95% CI: 1.44-36.58, P = 0.0165). CONCLUSION: Genetic predisposition was associated with the risk of AEs after DTaP-Hib vaccination, emphasizing the potential application in the prevention of AEs.


Asunto(s)
Vacunas contra Difteria, Tétanos y Tos Ferina Acelular , Predisposición Genética a la Enfermedad , Vacunas contra Haemophilus , Humanos , Lactante , Antígenos Bacterianos , Antígenos Virales , Estudios de Casos y Controles , China/epidemiología , Difteria/prevención & control , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/efectos adversos , Infecciones por Haemophilus/prevención & control , Haemophilus influenzae tipo b , Vacunas contra Haemophilus/efectos adversos , Tétanos/prevención & control , Vacunación/efectos adversos , Vacunas Combinadas/efectos adversos , Tos Ferina/prevención & control , Preescolar
19.
Front Genet ; 13: 905716, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36105080

RESUMEN

Genome-wide association studies (GWAS) have identified several common variants associated with polycystic ovary syndrome (PCOS). However, the etiology behind PCOS remains incomplete. Available evidence suggests a potential genetic correlation between PCOS and type 2 diabetes (T2D). The publicly available data may provide an opportunity to enhance the understanding of the PCOS etiology. Here, we quantified the polygenic overlap between PCOS and T2D using summary statistics of PCOS and T2D and then identified the novel genetic variants associated with PCOS behind this phenotypic association. A bivariate causal mixture model (MiXeR model) found a moderate genetic overlap between PCOS and T2D (Dice coefficient = 44.1% and after adjusting for body mass index, 32.1%). The conditional/conjunctional false discovery rate method identified 11 potential risk variants of PCOS conditional on associations with T2D, 9 of which were novel and 6 of which were jointly associated with two phenotypes. The functional annotation of these genetic variants supports a significant role for genes involved in lipid metabolism, immune response, and the insulin signaling pathway. An expression quantitative trait locus functionality analysis successfully repeated that 5 loci were significantly associated with the expression of candidate genes in many tissues, including the whole blood, subcutaneous adipose, adrenal gland, and cerebellum. We found that SCN2A gene is co-localized with PCOS in subcutaneous adipose using GWAS-eQTL co-localization analyses. A total of 11 candidate genes were differentially expressed in multiple tissues of the PCOS samples. These findings provide a new understanding of the shared genetic architecture between PCOS and T2D and the underlying molecular genetic mechanism of PCOS.

20.
PLoS One ; 17(6): e0268921, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35679336

RESUMEN

Understanding the temporal and spatial distribution characteristics of the cultural heritage of the Yellow River Basin can effectively improve the scientific understanding of the historical changes, environmental evolution, and cultural and economic development of the Yellow River Basin and thus provide a scientific and reasonable decision-making basis for the protection and development of its cultural heritage. The research object of this paper are the national cultural relic protection units. These are examined using the GIS spatial analysis method to explore the spatial and temporal distribution characteristics and spatial structure of 2,102 national material cultural heritage sites in the Yellow River basin. The results show that the spatial distribution of cultural heritage has a significant spatial agglomeration effect. The whole basin is concentrated in stable high- and low-value areas, and the difference between the high- and low-value areas is clear. Some aspects of the spatial structure heterogeneity are strong, showing a low value dispersion distribution trend. In different periods, the distribution direction and scope of cultural heritage have low ranges of rotation, a clear direction, and a high degree of centripetal distribution. The spatial and temporal distribution of cultural heritage is the result of the combined action of natural geographical environment such as climate change, topography, river hydrology, and human environment such as administrative institutional changes, ideological evolution, and social and economic development.


Asunto(s)
Hidrología , Ríos , China , Cambio Climático , Desarrollo Económico , Humanos , Ríos/química , Análisis Espacial
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