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1.
Risk Manag Healthc Policy ; 17: 623-631, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38524758

RESUMEN

Objective: To investigate the current nursing practice environment in Jinan, Shandong Province, and to identify the factors influencing the practice environment. Methods: This study is a cross-sectional study for nurses. From October to December 2022, using the clustering and stratified sampling methods, 2426 nurses from internal Medicine, Surgery, Obstetrics and Gynecology, Outpatient Department and Intensive Care Department of the Provincial Hospital of Shandong Medical University were selected and then investigated and analyzed using the revised Nurse Practice Environment Assessment Scale. Results: The overall mean evaluation of the practice environment scored 75.13±19.87, with a minimum value of 59.74 and a maximum value of 95.82. The items with higher scores were "the hospital has systematic training for new nurses", "the work system is perfect", and "the hospital can provide continuing education for nurses in accordance with the needs of their positions". The items with lower scores were "nurses enjoy legal benefits", "nurses have the opportunity to participate in hospital management decisions", and "nurses have the opportunity to participate in hospital internal management". The results of the multiple linear regression analysis of the factors influencing nurses' practice environment showed that gender, education, position, and years of work were independent influences on nurses' practice environment scores (p < 0.05), and they explained 48.127% of the variation in the total scores of the nurses' practice environment scale. The estimated values (ß) of sex, education, cheif nurse, nurses staff, work experience (year), and whether the only child variables were 3.141, 3.237, 2.713, 5.471, 2.074 and 0.732, respectively. Conclusion: The nurse practice environment still needs to be improved, mainly in terms of hospital management participation, human resource allocation and salary distribution system.

2.
Anal Chem ; 96(8): 3679-3685, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38353671

RESUMEN

Recently, organic photoelectrochemical transistor (OPECT) bioanalysis has become a prominent technique for the high-performance detection of biomolecules. However, as a sensitive index of the OPECT, the dynamic regulation transconductance (gm) is still severely deficient. Herein, this work reports a new photosensitive metal-organic framework (MOF-on-MOF) heterostructure for the effective modulation of maximum gm and natural bienzyme interfacing toward choline detection. Specifically, the bidentate ligand MOF (b-MOF) was assembled onto the UiO-66 MOF (u-MOF) by a modular assembly method, which could facilitate the charge separation and generate enhanced photocurrents and offer a biophilic environment for the immobilization of choline oxidase (ChOx) and horseradish peroxidase (HRP) through hydrogen-bonded bridges. The transconductance of the OPECT could be flexibly altered by increased light intensity to maximal value at zero gate bias, and sensitive choline detection was achieved with a detection limit of 0.2 µM. This work reveals the potential of MOF-on-MOF heterostructures for futuristic optobioelectronics.


Asunto(s)
Técnicas Biosensibles , Estructuras Metalorgánicas , Estructuras Metalorgánicas/química , Peroxidasa de Rábano Silvestre/química , Colina , Técnicas Biosensibles/métodos
3.
Brain Res ; 1826: 148740, 2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38142723

RESUMEN

INTRODUCTION: Catechol-O-methyltransferase (COMT) is a crucial enzyme involved in dopamine metabolism and has been implicated in the etiology of tardive dyskinesia (TD). We aimed to investigate the associations between COMT gene polymorphisms and the occurrence and severity of TD in a Chinese population, as well as the impact on the psychiatric symptoms and cognitive impairments observed in TD patients. METHODS: A total of 216 chronic schizophrenia patients, including 59 TD patients and 157 NTD patients, were recruited for this study. Three SNPs of the COMT gene (rs4680, rs165599 and rs4818) were selected and genotyped using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). TD severity, psychopathology and cognitive functioning were assessed using the Abnormal Involuntary Movement Scale (AIMS), the Positive and Negative Syndrome Scale (PANSS) and the Repeated Battery for Assessment of Neuropsychological Status (RBANS), respectively. RESULTS: In TD patients, total AIMs scores were higher in carriers of the rs4680 AA genotype than in carriers of the AG and GG genotypes (p = 0.01, 0.006), carriers of the rs4818 GC and CC genotypes had higher orofacial scores than in GG genotypes (p = 0.032, 0.002). In male TD patients, carriers of the rs165599 GA genotype scored lower in the extremities and trunk scores than AA genotype carriers (p = 0.015). Moreover, in male TD patients, COMT rs4818 was associated with cognition, since the C allele carriers had significantly higher immediate memory (p = 0.043) and verbal function (p = 0.040) scores than the G allele carriers. In addition, rs165599 genotype interacted with TD diagnosis on depressed factor (p = 0.031). CONCLUSION: Within the Chinese population, COMT gene polymorphisms could potentially serve as biomarkers for the symptoms and prognosis of TD patients.


Asunto(s)
Disfunción Cognitiva , Esquizofrenia , Discinesia Tardía , Humanos , Masculino , Discinesia Tardía/genética , Catecol O-Metiltransferasa/genética , Catecol O-Metiltransferasa/metabolismo , Genotipo , Polimorfismo de Nucleótido Simple/genética , Disfunción Cognitiva/genética
4.
Neuropsychiatr Dis Treat ; 19: 2499-2509, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38029048

RESUMEN

Objective: Tardive dyskinesia (TD) is a severe rhythmic movement disorder caused by long-term antipsychotic medication in chronic patients with schizophrenia (SCZ). We aimed to investigate the association between polymorphisms in oxidative stress-related genes (GSTM1, SOD2, NOS1, and NOS3) and adenosine receptor gene (ADORA2A), as well as their interactions, with the occurrence and severity of TD, and cognitive impairments in a Chinese Han population of SCZ patients. Methods: Two hundred and sixteen SCZ patients were recruited and divided into TD group (n=157) and non-TD group (n=59). DNA extraction was performed by a high-salt method, followed by SNP genotyping using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The severity of TD, psychopathology and cognitive functioning were assessed using the Abnormal Involuntary Movement Scale (AIMS), the Positive and Negative Syndrome Scale (PANSS) and the Repeated Battery for Assessment of Neuropsychological Status (RBANS), respectively. Results: The combination of GSTM1-rs738491, NOS1-rs738409 and ADORA2A-rs229883 was identified as the best three-point model to predict TD occurrence (p=0.01). Additionally, GSTM-rs738491 CC or NOS3-rs1800779 AG genotypes may be protective factors for psychiatric symptoms in TD patients. TD patients carrying the NOS1-rs738409 AG or ADORA2A-rs229883 TT genotypes exhibited poorer cognitive performance. Conclusion: Our findings suggest that the interaction of oxidative stress-related genes and adenosine receptor gene may play a role in the susceptibility and severity of TD in Chinese Han SCZ patient. Furthermore, these genes may also affect the psychiatric symptoms and cognitive function of TD patients.

5.
Brain Res ; 1821: 148579, 2023 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-37739333

RESUMEN

OBJECTIVE: Tardive dyskinesia (TD) is a medically induced movement disorder that occurs as a result of long-term use of antipsychotic medications, commonly seen in patients with schizophrenia (SCZ). The study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) of the CNR1 gene, TD and cognitive impairments in a Chinese population with SCZ. METHODS: A total of 216 SCZ patients were recruited. The participants were divided into TD and without TD (WTD) groups using the Schooler-Kane International Diagnostic Criteria. The severity of TD was assessed using the Abnormal Involuntary Movement Scale (AIMS). Cognitive function was assessed using the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) scale. Hardy-Weinberg equilibrium tests, chained disequilibrium analyses and haplotype analyses were performed using SHE-sis software. To explore the main effects of TD diagnosis, genotype and cognitive function, as well as interaction effects, analysis of covariance (ANCOVA) was employed. RESULTS: The prevalence of TD was approximately 27.3%. Significant differences were observed in the rs806368 CT genotype and rs806370 TC genotype within the hypercongenic pattern between the male TD and WTD groups (OR = 2.508, 95% CI: 1.055-5.961, p = 0.037; OR = 2.552, 95% CI: 1.073-6.069, p = 0.034). Among TD patients, those carrying the rs806368 CC genotype exhibited higher limb trunk scores (p < 0.05). Moreover, there was a statistically significant difference in visuospatial/construction between the TD and WTD groups (p = 0.04), and a borderline significant difference in visuospatial/construction when considering the interaction between TD diagnosis and genotype at the rs806368 locus (p = 0.05). CONCLUSION: CNR1 rs806368 and rs806370 polymorphisms may play a role in TD susceptibility. Additionally, CNR1 gene polymorphisms were associated with the severity of involuntary movements and cognitive impairments in TD patients.


Asunto(s)
Antipsicóticos , Disfunción Cognitiva , Receptor Cannabinoide CB1 , Esquizofrenia , Discinesia Tardía , Humanos , Masculino , Disfunción Cognitiva/tratamiento farmacológico , Pueblos del Este de Asia , Polimorfismo de Nucleótido Simple , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genética , Discinesia Tardía/genética , Discinesia Tardía/complicaciones , Discinesia Tardía/tratamiento farmacológico , Receptor Cannabinoide CB1/genética
6.
Ann Med ; 55(1): 2215539, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37243546

RESUMEN

OBJECTIVES: To evaluate the clinical utility of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in foetuses with oligohydramnios. METHODS: In this retrospective study, 126 fetuses with oligohydramnios at our centre from 2018 to 2021 were reviewed. The results of CMA and WES were analysed. RESULTS: One hundred and twenty-four cases underwent CMA and 32 cases underwent WES. The detection rate of pathogenic/likely pathogenic (P/LP) copy number variant (CNV) by CMA was 1.6% (2/124). WES revealed P/LP variants in 21.8% (7/32) of the foetuses. Six (85.7%, 6/7) foetuses showed an autosomal recessive inheritance pattern. Three (42.9%, 3/7) variants were involved in the renin-angiotensin-aldosterone system (RAAS), which are the known genetic causes of autosomal recessive renal tubular dysgenesis (ARRTD). CONCLUSION: CMA has low diagnostic utility for oligohydramnios, while WES offers obvious advantages in improving the detection rate. WES should be recommended for fetuses with oligohydramnios.


CMA has low diagnostic utility for oligohydramnios.WES offers obvious advantages for improving the detection over CMA, which improves pregnancy management, prenatal counselling and recurrence risk assessment for future pregnancies.


Asunto(s)
Oligohidramnios , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Secuenciación del Exoma , Oligohidramnios/genética , Análisis por Micromatrices , Feto , Diagnóstico Prenatal
7.
Biosens Bioelectron ; 236: 115417, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37244084

RESUMEN

Total antioxidant capacity (TAC) has become an important index to evaluate the food quality. Effective antioxidant detection has been the research hotspot of scientists. In this work, a novel three-channel colorimetric sensor array founded on Au2Pt bimetallic nanozymes for the discrimination of antioxidants in food was constructed. Benefiting from the unique bimetallic doping structure, Au2Pt nanospheres exhibited the excellent peroxidase-like activity with Km of 0.044 mM and Vmax of 19.37 × 10-8 M s-1 toward TMB. The density functional theory (DFT) calculation revealed that Pt atom in the doping system was active sites and there was no energy barrier in catalytic reaction which made Au2Pt nanospheres had excellent catalytic activity. Accordingly, a multifunctional colorimetric sensor array was constructed based on Au2Pt bimetallic nanozymes for rapid and sensitive detection of five antioxidants. Based on the different reduction ability of antioxidants, oxidized TMB could be reduced in different degrees. In the presence of H2O2, the colorimetric sensor array could generate differential colorimetric signals (fingerprints) by using TMB as the chromogenic substrate, which could be accurately discriminated through linear discriminant analysis (LDA) with a detection limit of <0.2 µM. The sensor array was able to the evaluate TAC in three actual samples (milk, green tea and orange juice). Furthermore, we prepared a rapid detection strip to meet the needs of practical application, making a positive contribution to food quality evaluation.


Asunto(s)
Antioxidantes , Técnicas Biosensibles , Antioxidantes/análisis , Colorimetría , Peróxido de Hidrógeno/análisis ,
8.
Angew Chem Int Ed Engl ; 62(29): e202302930, 2023 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-37189290

RESUMEN

Single-cell epigenetics is envisioned to decipher manifold epigenetic phenomena and to contribute to our accurate knowledge about basic epigenetic mechanisms. Engineered nanopipette technology has gained momentum in single-cell studies; however, solutions to epigenetic questions remain unachieved. This study addresses the challenge by exploring N6-methyladenine (m6 A)-bearing deoxyribozyme (DNAzyme) confined within a nanopipette for profiling a representative m6 A-modifying enzyme, fat mass and obesity-associated protein (FTO). Electroosmotic intracellular extraction of FTO could remove the m6 A and cause DNAzyme cleavage, leading to the altered ionic current signal. Because the cleavage can release a DNA sequence, we simultaneously program it as an antisense strand against FTO-mRNA, intracellular injection of which has been shown to induce early stage apoptosis. This nanotool thus features the dual functions of studying single-cell epigenetics and programmable gene regulation.


Asunto(s)
ADN Catalítico , ADN Catalítico/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Regulación de la Expresión Génica , Epigénesis Genética , ARN Mensajero/metabolismo
9.
Brain Behav ; 13(5): e3002, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37062964

RESUMEN

OBJECTIVE: Facial expressions have been served as clinical symptoms to convey mental conditions in psychiatry. This paper proposes to recognize patients with schizophrenia (SCZ) using their facial images based on deep learning algorithm, and to investigate objective differences in facial expressions between SCZ patients and healthy controls using deep learning algorithm and statistical analyses. METHODS: The study consists of two parts. The first part recruited 106 SCZ patients and 101 healthy controls, and videotaped their facial expressions through a fixed experimental paradigm. The video data were randomly divided into two sets, one for training a convolutional neural network (CNN) with the classification of "healthy control" or "SCZ patient" as output and the other for evaluating the classification result of the trained CNN. In the second part, all facial images of the recruited participants were put into another CNN separately, which was priorly trained with a facial expression database and will output the most likely facial expressions of the recruited participants. Statistical analyses were performed on the obtained facial expressions to find out the objective differences in facial expressions between the two recruited groups. RESULTS: The trained CNN achieved an overall accuracy of 95.18% for classifying "healthy control" or "SCZ patient." Statistical results on the obtained facial expressions demonstrated that the objective differences between the two recruited groups were statistically significant (p < .05). CONCLUSIONS: Facial expressions hold great promise as SCZ clues with the help of deep learning algorithm. The proposed approach would be potentially applied to mobile devices for autorecognizing SCZ in the context of clinical and daily life.


Asunto(s)
Expresión Facial , Esquizofrenia , Humanos , Algoritmos , Bases de Datos Factuales , Redes Neurales de la Computación , Esquizofrenia/diagnóstico , Estudios de Casos y Controles
10.
Front Genet ; 14: 1032346, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36923788

RESUMEN

Background: Prenatal diagnosis of fetal short long bones (SLBs) was reported to be associated with skeletal dysplasias, chromosomal abnormalities, and genetic syndromes. This study aims to identify the genetic causes for fetal short long bones, and retrospectively evaluate the additional diagnostic yield of exome sequencing (ES) for short long bones following the use of conventional genetic testing. Methods: A cohort of ninety-four fetuses with sonographically identified short long bones was analyzed by trio-exome sequencing between January 2016 and June 2021. Fetuses with abnormal results of karyotype or chromosomal microarray analysis were excluded. Variants were interpreted based on ACMG/AMP guidelines. All diagnostic de novo variants were validated by Sanger sequencing. Results: Of the 94 fetuses, 38 (40.4%) were found to carry causal genetic variants (pathogenic or likely pathogenic) in sixteen genes with 38 variants. Five fetuses (5.3%) had variant(s) of uncertain significance. Thirty-five cases (37.2%) were diagnosed as genetic skeletal dysplasias including 14 different diseases that were classified into 10 groups according to the Nosology and Classification of Genetic Skeletal Disorders. The most common disease in the cohort was achondroplasia (28.9%), followed by osteogenesis imperfecta (18.4%), thanatophoric dysplasia (10.5%), chondrogenesis (7.9%), and 3-M syndrome (5.3%). The diagnostic yield in fetuses with isolated short long bones was lower than the fetuses with non-isolated short long bones, but not reached statistical significance (27.3% vs. 44.4%; p = 0.151). Whereas, the rate in the fetuses with other skeletal abnormalities was significantly higher than those with non-skeletal abnormalities (59.4% vs. 32.5%, p = 0.023), and the diagnostic rate was significantly higher in femur length (FL) below -4SDs group compared with FL 2-4SDs below GA group (72.5% vs. 16.7%; p < 0.001). A long-term follow-up showed that outcomes for fetuses with FL 2-4SDs below GA were significantly better than those with FL below -4SDs. Additionally, fourteen (36.8%) novel short long bones-related variants were identified in the present study. Conclusion: The findings suggest that in fetuses with short long bones routine genetic tests failed to determine the underlying causes, exome sequencing could add clinically relevant information that could assist the clinical management of pregnancies. Novel pathogenic variants identified may broaden the mutation spectrum for the disorders and contributes to clinical consultation and subsequent pregnancy examination.

11.
Matern Child Health J ; 27(3): 548-555, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36732464

RESUMEN

OBJECTIVES: Joyuus is a culturally diverse, comprehensive online tool designed to address the self-care needs of underserved postpartum women. The tool provides actionable self-care information, knowledge, and skills to improve postpartum health and identifies red flags for when self-care shifts to seeking care. METHODS: We employed a mixed-methods multiphase design to evaluate the Joyuus prototype, including a pre-post evaluation (N = 87) to assess behavioral health outcomes before and after using the tool for a one-month period. 91% completed the post-test (N = 79). The analysis focused on estimation of treatment effect (via 95% confidence intervals) and fitness of instruments in this population. RESULTS: Participants were between 6 months pregnant and one year postpartum, a mean age of 30 years, 100% female, 99% Black, with nearly equal distribution of married (55%) and not married (44%), and above (47%) and below (46%) annual income of $60 K. Key measures saw significant improvement from pre- (mean = 26.44, SD = 5.39) to post (mean = 28.29, SD = 5.26) on the Connor-Davidson Resilience Scale (p < 0.001) Trends toward improvement (not statistically significant) were noted for Depression (EPDS) (p = 0.624) and Anxiety (STAI) (p = 0.286), and no meaningful change on MOS Social Support or COVID-19 Mental Health Impacts Measures. CONCLUSIONS FOR PRACTICE: This pilot study demonstrates that a self-care mobile tool has the potential to address significant health outcomes related to maternal morbidity and mortality. By providing a continuously available companion addressing physical, mental, and real-life questions, it creates value during postpartum for mothers who can often feel overwhelmed or isolated.


Asunto(s)
COVID-19 , Depresión Posparto , Embarazo , Humanos , Femenino , Adulto , Masculino , Proyectos Piloto , Autocuidado , Periodo Posparto , Internet , Depresión Posparto/terapia
12.
Angew Chem Int Ed Engl ; 62(9): e202215801, 2023 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-36550087

RESUMEN

Single-cell protein therapeutics is expected to promote our in-depth understanding of how a specific protein with a therapeutic dosage treats the cell without population averaging. However, it has not yet been tackled by current single-cell nanotools. We address this challenge by the use of a double-barrel nanopipette, in which one lumen was used for electroosmotic cytosolic protein delivery and the other was customized for ionic evaluation of the consequence. Upon injection of protein DJ-1 through the delivery lumen, upregulation of the antioxidant protein could protect neural PC-12 cells against oxidative stress from phorbol myristate acetate exposure, as deduced by targeting of the cytosolic hydrogen peroxide by the detecting lumen. The nanotool developed in this study for single-cell protein therapeutics provides a perspective for future single-cell therapeutics involving different therapeutic modalities, such as peptides, enzymes and nucleic acids.


Asunto(s)
Tratamiento Basado en Trasplante de Células y Tejidos , Proteína Desglicasa DJ-1 , Iones , Péptidos , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Sistema de Administración de Fármacos con Nanopartículas , Proteína Desglicasa DJ-1/farmacología , Proteína Desglicasa DJ-1/uso terapéutico , Estrés Oxidativo , Acetato de Tetradecanoilforbol
13.
Clin Rheumatol ; 42(2): 539-548, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36374433

RESUMEN

OBJECTIVE: This study screened out the key genes associated with the occurrence and development of lupus nephritis (LN) using bioinformatics methods, and then explored the expression of key genes in LN and the inhibitory effect of triptolide. METHODS: The GEO2R online tool in the GEO database was used to perform differential analysis of gene expression in LN tissues and normal kidney tissues. The GO function and KEGG pathway enrichment analysis of differentially expressed genes (DEGs), STRING, and Cytoscape software were used to build a protein-protein interaction network (PPI) to screen out the Hub gene. Mouse glomerular mesangial cells (MMC) were randomly divided into a control group, an interferon-γ (IFN-γ) stimulation group, and a triptolide intervention group. The relative expression of CXCL10 mRNA in each group was detected by real-time fluorescent quantitative PCR (RT-PCR). CXCL10 secretion was detected by enzyme-linked immunosorbent assay (ELISA), and Western blot was used to detect the expression of the JAK/STAT1 signaling pathway-related proteins STAT1 and p-STAT1 in each group. RESULTS: Bioinformatics showed that there were 22 DEGs expression differences in the GEO database. The GO enrichment analysis showed that biological process (BP) such as the type I interferon signaling pathway, innate immune response, IFN-γ-mediated signaling pathway, virus defense response, and immune response were significantly regulated by DEGs. Through the combination of String database analysis and cytoscape software, it was found that STAT1 and CXCL10 are closely related to LN. Experimental results showed that IFN-γ induces the expression of CXCL10 mRNA and protein by activating the JAK/STAT1 signaling pathway, while triptolide inhibits the expression of CXCL10 mRNA and protein by inhibiting the JAK/STAT1 signaling pathway. CONCLUSION: STAT1 and CXCL10 are the key genes in the occurrence and development of LN. IFN-γ induces the expression of CXCL10 by activating the JAK/STAT1 signaling pathway, while triptolide inhibits the expression of CXCL10 by blocking the JAK/STAT1 signaling pathway. Inhibition of the JAK/STAT1 signaling pathway and CXCL10 expression is expected to become a potential target for the treatment of LN. Key Points • Bioinformatics showed that there were 22 DEGs expression differences in the GEO database. • Through the combination of String database analysis and Cytoscape software, it was found that STAT1 and CXCL10 are closely related to LN. • Experimental results showed that IFN-γ induces the expression of CXCL10 mRNA and protein by activating the JAK/STAT1 signaling pathway, while triptolide inhibits the expression of CXCL10 mRNA and protein by inhibiting the JAK/STAT1 signaling pathway.


Asunto(s)
Quimiocina CXCL10 , Nefritis Lúpica , Factor de Transcripción STAT1 , Animales , Ratones , Biología Computacional , Interferón gamma , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/genética , ARN Mensajero/genética , Transducción de Señal , Factor de Transcripción STAT1/genética , Quimiocina CXCL10/genética , Antiinflamatorios no Esteroideos/farmacología
14.
Front Pharmacol ; 13: 950571, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36210843

RESUMEN

BRAF inhibitors are commonly used in targeted therapies for melanoma patients harboring BRAFV600E mutant. Despite the benefit of vemurafenib therapy, acquired resistance during or after treatment remains a major obstacle in BRAFV600E mutant melanoma. Here we found that RSK2 is overexpressed in melanoma cells and the high expression of RSK2 indicates poor overall survival (OS) in melanoma patients. Overexpression of RSK2 leads to vemurafenib resistance, and the deletion of RSK2 inhibits cell proliferation and sensitizes melanoma cells to vemurafenib. Mechanistically, RSK2 enhances the phosphorylation of FOXO1 by interacting with FOXO1 and promoting its subsequent degradation, leading to upregulation of cyclin D1 in melanoma cells. These results not only reveal the presence of a RSK2-FOXO1-cyclin D1 signaling pathway in melanoma, but also provide a potential therapeutic strategy to enhance the efficacy of vemurafenib against cancer.

15.
Angew Chem Int Ed Engl ; 61(47): e202212752, 2022 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-36173932

RESUMEN

Rational utilization of the rich light-bio-matter interplay taking place in single-cell analysis represents a new technological direction in the field. The light-fueled operation is expected to achieve advanced photoelectrochemical (PEC) single-cell analysis with unknown possibilities. Here, a PEC nanoreactor capable of single-cell sampling and near zero-background Faradaic detection of intracellular microRNA (miR) is devised by the construction of a small reaction chamber accommodating the target-triggered hybridization chain reaction for binding the metallointercalator of [Ru(bpy)2 (dppz)]2+ as the signal reporter. Light stimulation of the dsDNA/metallointercalator adduct will induce the generation of photocurrents, underpinning a zero-biased and near zero-background PEC method toward Faradaic detection of non-electrogenic miR at the single-cell level. Using this nanotool, lower miR concentration in the near-nucleus region than that in the main cytosol was revealed.


Asunto(s)
Técnicas Biosensibles , MicroARNs , MicroARNs/análisis , ADN/metabolismo , Hibridación de Ácido Nucleico , Nanotecnología , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Límite de Detección
16.
Ann Med ; 54(1): 1297-1302, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35506821

RESUMEN

OBJECTIVES: To evaluate the efficiency of chromosomal microarray analysis (CMA) in the prenatal diagnosis of foetuses with isolated absent or hypoplastic nasal bone (NB) in the first and second trimester. METHODS: From January 2015 to April 2021, foetuses with isolated absent or hypoplastic NB who received invasive prenatal diagnosis were enrolled. The results of CMA were analysed. RESULTS: There were 221 foetuses, including 166 cases with isolated absent NB and 55 cases with isolated hypoplastic NB. Twenty-four foetuses (10.9%, 24/221) had an ultrasonic diagnosis in the first trimester and 197 (89.1%, 197/221) had a ultrasonic diagnosis in the second trimester. The overall diagnostic yield of CMA was 9.0% (20/221). Aneuploidies were detected in 13 (5.9%, 13/221) foetuses, including 10 Down syndrome, 2 Klinefelter's syndrome and 1 trisomy 18. Pathogenic copy number variations (CNVs) were detected in seven foetuses (3.2%, 7/221). In addition, variants of unknown significance (VOUS) were detected in four foetuses. The foetuses with isolated absent NB had a higher detection rate of chromosome abnormality than the isolated hypoplastic NB, but the difference was not significant in the statistical analysis (10.2% vs. 5.5%, χ2 =0.642, p = .423). No significant difference was observed in the detection rate between the first trimester and the second trimester (16.6% vs. 8.1%, χ2 = 1.002, p = .317, Chi-square test). CONCLUSION: CMA can increase the diagnostic yield of chromosome abnormality, especially pathogenic CNVs for foetuses with isolated absent or hypoplastic NB. CMA should be recommended when isolated absent or hypoplastic NB is suspected antenatally.7.


Asunto(s)
Variaciones en el Número de Copia de ADN , Hueso Nasal , Aberraciones Cromosómicas , Femenino , Feto , Humanos , Análisis por Micromatrices/métodos , Hueso Nasal/diagnóstico por imagen , Embarazo , Diagnóstico Prenatal/métodos
17.
Front Microbiol ; 13: 819654, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35401442

RESUMEN

Low detection rates of Mycobacterium tuberculosis (MTB) by culture and smear microscopy prevent early diagnosis of tuberculosis (TB) in children. Therefore, developing rapid and accurate diagnostic techniques are critical to achieving the global aim of minimizing childhood TB. The present study was performed to evaluate the diagnostic effectiveness of the novel cross-priming amplification-based EasyNAT MTB complex assay (EasyNAT) in childhood TB. Five hundred and six children with suspected TB were enrolled from January 2018 to October 2021. Gastric aspirate (GA) samples were tested by bacterial culture, acid-fast bacillus microscopy, EasyNAT, Xpert MTB/RIF (Xpert), or Xpert MTB/RIF Ultra (Xpert Ultra). Among 239 children simultaneously tested by EasyNAT and Xpert methods, both assays showed similar sensitivities in total active TB cases [22.6% (31/137) vs. 26.3% (36/137), p = 0.441] and in bacteriologically confirmed TB cases [both 60.0% (9/15)]. The two assays presented similar specificities of 98.0% (100/102) and 99.0% (101/102), respectively (p = 1.000). Among 267 children who were simultaneously tested with EasyNAT and Xpert Ultra, Xpert Ultra demonstrated higher sensitivity than EasyNAT in total active TB cases [50.9% (89/175) vs. 30.3% (53/175), p < 0.001]. EasyNAT and Xpert Ultra yielded similar specificities, at 97.8% (90/92) and 100.0% (92/92), respectively (p = 0.155). These findings indicated that Xpert Ultra was superior to EasyNAT despite its higher cost and EasyNAT was not inferior to Xpert in the diagnosis of childhood TB using GA samples. EasyNAT may therefore be a suitable alternative diagnostic method for childhood TB based on its cost-effectiveness, speed, and accuracy.

18.
Anal Chim Acta ; 1199: 339560, 2022 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-35227381

RESUMEN

Target biomarker detection with high accuracy in biological sample is necessary for the constructed immunoassays. Herein, a novel and enhanced cathodic immunosensor supported by photoanode was designed for sensitive and specific detection of human chorionic gonadotropin (HCG). Specifically, the electrode of TiO2 nanotube with N doping (TiO2:N) was fabricated and assembled with AgInS2 quantum dots (QDs) to acquire the TiO2:N/AgInS2 photoanode. For the sensing cathode, Pt nanoparticles (NPs) were decorated on carbon nanotubes (CNTs) to prepare the CNT/Pt cathodic matrix and was used to modify capture HCG antibody (Ab). In this photoelectrochemical (PEC) sensing system, the TiO2:N/AgInS2 photoanode served as the signal-converting element to produce prominent current signal, while the immune recognition events occurred on the sensing cathode to evidently change the initial current signal from steric hindrance effect. Profiting by excellent photoelectric property and good anti-interference ability of this featured PEC system, the developed cathodic immunosensor demonstrated high sensitivity and specificity for the detection of target HCG antigen (Ag). This photoanode-supported cathodic sensing strategy provided a potential path forward to exploit other enhanced PEC immunosensors in the application of biological samples.


Asunto(s)
Técnicas Biosensibles , Nanotubos de Carbono , Gonadotropina Coriónica , Técnicas Electroquímicas , Electrodos , Humanos , Inmunoensayo , Límite de Detección , Titanio/química
19.
J Matern Fetal Neonatal Med ; 35(16): 3152-3157, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32907415

RESUMEN

OBJECTIVE: To compare prenatal and perinatal outcomes of twin pregnancies in which one twin the nuchal translucency (NT) was above the 95th percentile in dichorionic twins (DCT) and monochorionic twins (MCT). METHOD: In this retrospective study, 93 twin pregnancies (186 fetuses) in which one twin the NT was above the 95th percentile and the co-twin had normal NT were analyzed. Results of of G-banding and Chromosomal microarray (CMA), ultrasound findings and pregnancy outcomes were reviewed. RESULTS: Totally, 57 pregnancies (114 fetuses) were DCT and 36 pregnancies (72 fetuses) were MCT. Karyotyping and CMA results shown that clinically significant chromosomal abnormalities were found in 16 fetuses, including 13 aneuploidies, 2 chromosomal mosaic and 1 pathological Copy number variations (CNVs) (14 were DCT and 2 were MCT). Overall, the incidence of fetal chromosomal abnormalities was 12.3% (14/114) in DCT and 2.8%(2/72) in MCT (χ2 = 3.932, p = 0.047). Among the cases with normal prenatal diagnosis result, structural abnormalities were found in four fetuses (4.0%, 4/100) in DCT and two fetuses (2.9%, 2/70) in MCT (p > 0.999). There were one intrauterine fetal demises (IUFD) and two miscarry in DCT. One IUFD, three subsequently developed Twin-to-Twin Transfusion Syndrome (TTTS) and four developed selective intrauterine growth restriction (sIUGR) in MCT. Totally, the overall fetal survival rate was 85.1% (97/114) in DCT and 80.6% (58/72) in MCT (χ2 = 0.653, p = 0.419). CONCLUSION: Compared to MCT, the incidence of chromosomal abnormalities in DCT discordant for one fetus with NT above the 95th percentile was higher. The risk of structural abnormalities and the rate of fetal survival for both MCT and DCT was similar.


Asunto(s)
Medida de Translucencia Nucal , Embarazo Gemelar , Aberraciones Cromosómicas , Variaciones en el Número de Copia de ADN , Femenino , Feto/diagnóstico por imagen , Humanos , Medida de Translucencia Nucal/métodos , Embarazo , Estudios Retrospectivos , Gemelos Dicigóticos , Ultrasonografía Prenatal
20.
Eur J Clin Microbiol Infect Dis ; 41(2): 235-243, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34734347

RESUMEN

Microbiological confirmation is rare in children with active tuberculosis; therefore, a more accurate test is needed to detect pulmonary tuberculosis in children. In this multicenter study, we evaluated the utility of the Xpert MTB/RIF Ultra (Ultra) on sputum, an assay recommended by the World Health Organization to test for childhood tuberculosis in high-burden settings. Children with symptoms suggestive of tuberculosis were enrolled at three hospitals in China and categorized as having active tuberculosis or nontuberculosis. The sensitivity and specificity of Ultra were 42.1% (48/114) and 99.0% (208/210), respectively. Using three MTB culture results as the reference, the sensitivity of Ultra in the subset of 38 children with culture-positive and 76 children with culture-negative was 68.4% (26/38) and 28.9% (22/76), respectively(p < 0.001). A single MTB culture combined with a single Ultra could detect 54 (54/114,47.4%) cases with active TB, while repeated MTB culture combined with a single Ultra detected 60 (60/114, 52.6%) cases with active TB(p = 0.427). Among 155 children (58 with TB and 97 with RTIs) simultaneously tested with the Ultra and Xpert MTB/RIF (Xpert), the sensitivity of the Xpert (24.1%, 14/58) was lower than that of the Ultra (41.4%, 24/58; p = 0.048). Eight children were found to have rifampin-resistant MTB strains. The Xpert MTB/RIF Ultra assay should be implemented to test for pulmonary tuberculosis in children to achieve higher confirmation rates.


Asunto(s)
Antibióticos Antituberculosos/farmacología , Rifampin/farmacología , Esputo/microbiología , Tuberculosis Pulmonar/diagnóstico , Adolescente , Niño , Preescolar , China , Pruebas Diagnósticas de Rutina , Farmacorresistencia Bacteriana/efectos de los fármacos , Humanos , Lactante , Recién Nacido , Mycobacterium tuberculosis/efectos de los fármacos , Estudios Retrospectivos , Sensibilidad y Especificidad , Tuberculosis/diagnóstico
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