Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 226
Filtrar
Más filtros

Intervalo de año de publicación
1.
Cell ; 186(5): 1026-1038.e20, 2023 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-36868208

RESUMEN

Down syndrome (DS) is a neurological disorder with multiple immune-related symptoms; however, crosstalk between the CNS and peripheral immune system remains unexplored. Using parabiosis and plasma infusion, we found that blood-borne factors drive synaptic deficits in DS. Proteomic analysis revealed elevation of ß2-microglobulin (B2M), a major histocompatibility complex class I (MHC-I) component, in human DS plasma. Systemic administration of B2M in wild-type mice led to synaptic and memory defects similar to those observed in DS mice. Moreover, genetic ablation of B2m or systemic administration of an anti-B2M antibody counteracts synaptic impairments in DS mice. Mechanistically, we demonstrate that B2M antagonizes NMDA receptor (NMDAR) function through interactions with the GluN1-S2 loop; blocking B2M-NMDAR interactions using competitive peptides restores NMDAR-dependent synaptic function. Our findings identify B2M as an endogenous NMDAR antagonist and reveal a pathophysiological role for circulating B2M in NMDAR dysfunction in DS and related cognitive disorders.


Asunto(s)
Síndrome de Down , Receptores de N-Metil-D-Aspartato , Microglobulina beta-2 , Animales , Humanos , Ratones , Microglobulina beta-2/metabolismo , Microglobulina beta-2/farmacología , Disfunción Cognitiva/metabolismo , Reacciones Cruzadas , Parabiosis , Proteómica , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Síndrome de Down/sangre , Síndrome de Down/metabolismo
2.
PLoS Pathog ; 19(12): e1011885, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38117848

RESUMEN

Small RNAs act as fungal pathogen effectors that silence host target genes to promote infection, a virulence mechanism termed cross-kingdom RNA interference (RNAi). The essential pathogen factors of cross-kingdom small RNA production are largely unknown. We here characterized the RNA-dependent RNA polymerase (RDR)1 in the fungal plant pathogen Botrytis cinerea that is required for pathogenicity and cross-kingdom RNAi. B. cinerea bcrdr1 knockout (ko) mutants exhibited reduced pathogenicity and loss of cross-kingdom small RNAs. We developed a "switch-on" GFP reporter to study cross-kingdom RNAi in real-time within the living plant tissue which highlighted that bcrdr1 ko mutants were compromised in cross-kingdom RNAi. Moreover, blocking seven pathogen cross-kingdom small RNAs by expressing a short-tandem target mimic RNA in transgenic Arabidopsis thaliana led to reduced infection levels of the fungal pathogen B. cinerea and the oomycete pathogen Hyaloperonospora arabidopsidis. These results demonstrate that cross-kingdom RNAi is significant to promote host infection and making pathogen small RNAs an effective target for crop protection.


Asunto(s)
Arabidopsis , ARN Polimerasa Dependiente del ARN , Interferencia de ARN , ARN Interferente Pequeño/genética , ARN Polimerasa Dependiente del ARN/genética , Arabidopsis/genética , Arabidopsis/microbiología , Virulencia/genética , Plantas/genética , Botrytis/genética , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , ARN de Hongos/genética , ARN de Planta
3.
BMC Biol ; 22(1): 12, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38273307

RESUMEN

BACKGROUND: Many viruses enter host cells by hijacking endosomal trafficking. CapZ, a canonical actin capping protein, participates in endosomal trafficking, yet its precise role in endocytosis and virus infection remains elusive. RESULTS: Here, we showed that CapZ was transiently associated with early endosomes (EEs) and was subsequently released from the matured EEs after the fusion of two EEs, which was facilitated by PI(3)P to PI(3,5)P2 conversion. Vacuolin-1 (a triazine compound) stabilized CapZ at EEs and thus blocked the transition of EEs to late endosomes (LEs). Likewise, artificially tethering CapZ to EEs via a rapamycin-induced protein-protein interaction system blocked the early-to-late endosome transition. Remarkably, CapZ knockout or artificially tethering CapZ to EEs via rapamycin significantly inhibited flaviviruses, e.g., Zika virus (ZIKV) and dengue virus (DENV), or beta-coronavirus, e.g., murine hepatitis virus (MHV), infection by preventing the escape of RNA genome from endocytic vesicles. CONCLUSIONS: These results indicate that the temporal association of CapZ with EEs facilitates early-to-late endosome transition (physiologically) and the release of the viral genome from endocytic vesicles (pathologically).


Asunto(s)
Fosfatos de Fosfatidilinositol , Infección por el Virus Zika , Virus Zika , Animales , Humanos , Ratones , Endocitosis/fisiología , Endosomas/metabolismo , Sirolimus/farmacología , Sirolimus/metabolismo , Vesículas Transportadoras , Internalización del Virus , Infección por el Virus Zika/metabolismo
4.
Phys Rev Lett ; 132(23): 231802, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38905664

RESUMEN

We present the results for the complete next-to-leading order electroweak corrections to pp→HH at the Large Hadron Collider, focusing on the dominant gluon-gluon fusion process. While the corrections at the total cross-section level are approximately -4%, those near the energy of HH production threshold exceed +15%, and corrections at the high-energy region are around -10%, leading to a shape distortion for the differential distributions. Our findings substantially diminish the theoretical uncertainties associated with this pivotal process, providing valuable input for understanding the shape of the Higgs boson potential upon comparison with experimental measurements.

5.
BMC Cancer ; 24(1): 610, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773439

RESUMEN

BACKGROUND: Venous thromboembolism (VTE) is a major complication of breast cancer surgical patients. Assessing VTE awareness enables medical staff to tailor educational programs that improve patient self-management and reduce VTE risk. Therefore, this study aimed to assess VTE awareness among breast cancer surgical patients and identify factors influencing their awareness level. METHODS: A multicenter cross-sectional study was conducted on breast cancer patients scheduled for surgery from May 2023 to November 2023. Data were collected using a general information form and a validated self-assessment questionnaire on VTE awareness for breast cancer surgical patients. Univariate analysis and multiple linear regression analysis were used to analyze the data. RESULTS: Of 1969 patients included, the term awareness rates for deep vein thrombosis and pulmonary embolism were 42.5% and 26.1%, respectively. Information about VTE was primarily obtained from doctors (30.4%), nurses (24.0%), and social media (23.3%). The overall average VTE awareness score was 1.55 ± 0.53, with the dimension of VTE preventive measures scoring highest, and VTE clinical symptoms/signs scoring lowest. Multivariate analysis identified education level, personal VTE history, chemotherapy and surgical history, and the hospital's regional location as significant factors associated with VTE awareness level (p < 0.05). CONCLUSION: This study highlights a critical need for improved VTE awareness among breast cancer surgical patients, particularly regarding clinical symptoms/signs. Health education programs are recommended especially tailored for patients with lower education levels, no history of VTE, or without prior surgery or chemotherapy, to improve their understanding of VTE.


Asunto(s)
Neoplasias de la Mama , Conocimientos, Actitudes y Práctica en Salud , Tromboembolia Venosa , Humanos , Femenino , Estudios Transversales , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/complicaciones , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/epidemiología , Persona de Mediana Edad , Adulto , Factores de Riesgo , Encuestas y Cuestionarios , Anciano , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control
6.
Mol Biol Rep ; 51(1): 351, 2024 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-38400865

RESUMEN

The nervous system possesses the remarkable ability to undergo changes in order to store information; however, it is also susceptible to damage caused by invading pathogens or neurodegenerative processes. As a member of nucleotide-binding oligomerization domain-like receptor (NLR) family, the NLRP6 inflammasome serves as a cytoplasmic innate immune sensor responsible for detecting microbe-associated molecular patterns. Upon activation, NLRP6 can recruit the adapter protein apoptosis-associated speck-like protein (ASC) and the inflammatory factors caspase-1 or caspase-11. Consequently, inflammasomes are formed, facilitating the maturation and secretion of pro-inflammatory cytokines such as inflammatory factors-18 (IL-18) and inflammatory factors-1ß (IL-1ß). Precise regulation of NLRP6 is crucial for maintaining tissue homeostasis, as dysregulated inflammasome activation can contribute to the development of various diseases. Furthermore, NLRP6 may also play a role in the regulation of extraintestinal diseases. In cells of the brain, such as astrocytes and neurons, NLRP6 inflammasome are also present. Here, the assembly and subsequent activation of caspase-1 mediated by NLRP6 contribute to disease progression. This review aims to discuss the structure and function of NLRP6, explain clearly the mechanisms that induce and activate NLRP6, and explore its role within the central and peripheral nervous system.


Asunto(s)
Inflamasomas , Enfermedades del Sistema Nervioso , Humanos , Inflamasomas/metabolismo , Citocinas/metabolismo , Caspasa 1/metabolismo , Apoptosis , Enfermedades del Sistema Nervioso/genética , Caspasas , Péptidos y Proteínas de Señalización Intracelular
7.
Pak J Pharm Sci ; 37(1(Special)): 205-213, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38747271

RESUMEN

In this study, a sensitive high-performance liquid chromatography detector was established and validated for the simultaneous determination of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone in Liuwei Muxiang Capsules. The analysis was achieved on CHANIN 100-5-C18-H column (5µm, 250 mm×4.6 mm) with the temperature of 30oC. Gradient elution was applied using 0.1% phosphoric acid solution-methanol-acetonitrile (50:50) as mobile phase at the flow rate of 1.0 mL/min. The determination was performed at the wavelength of 225 nm (detecting geniposide), 254 nm (detecting ellagic acid), 343 nm (detecting piperine) and 225 nm (detecting costunolide and dehydrocostuslactone) along with the sample volume of 10µL. The linear ranges of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone demonstrated good linear relationships within their respective determination ranges. The average recoveries were 100.04%, 99.86%, 99.79%, 100.17% and 100.41%, respectively. RSD% was 1.3%, 1.2%, 1.2%, 1.2%, 1.5%, respectively. The developed method was proved to be simple, accurate and sensitive, which can provide a quantitative analysis method for the content determination of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone in Liuwei Muxiang capsules.


Asunto(s)
Alcaloides , Benzodioxoles , Cápsulas , Medicamentos Herbarios Chinos , Ácido Elágico , Iridoides , Lactonas , Piperidinas , Alcamidas Poliinsaturadas , Cromatografía Líquida de Alta Presión/métodos , Benzodioxoles/análisis , Alcamidas Poliinsaturadas/análisis , Piperidinas/análisis , Piperidinas/química , Alcaloides/análisis , Lactonas/análisis , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Iridoides/análisis , Ácido Elágico/análisis , Reproducibilidad de los Resultados , Sesquiterpenos/análisis
8.
BMC Bioinformatics ; 24(1): 387, 2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37821827

RESUMEN

BACKGROUND: Metagenomic sequencing is an unbiased approach that can potentially detect all the known and unidentified strains in pathogen detection. Recently, nanopore sequencing has been emerging as a highly potential tool for rapid pathogen detection due to its fast turnaround time. However, identifying pathogen within species is nontrivial for nanopore sequencing data due to the high sequencing error rate. RESULTS: We developed the core gene alleles metagenome strain identification (cgMSI) tool, which uses a two-stage maximum a posteriori probability estimation method to detect pathogens at strain level from nanopore metagenomic sequencing data at low computational cost. The cgMSI tool can accurately identify strains and estimate relative abundance at 1× coverage. CONCLUSIONS: We developed cgMSI for nanopore metagenomic pathogen detection within species. cgMSI is available at https://github.com/ZHU-XU-xmu/cgMSI .


Asunto(s)
Secuenciación de Nanoporos , Nanoporos , Metagenoma , Alelos , Metagenómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
9.
Mol Genet Genomics ; 298(6): 1493-1503, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37845373

RESUMEN

Previous studies have observed relationships between immune cells and systemic lupus erythematosus (SLE), but their causal links remain undetermined. Based on the public available genome-wide association studies (GWAS) summary statistics, we conducted two-sample Mendelian randomization (MR) to evaluate the associations between 731 immune phenotypes and SLE pairs. Pairwise pleiotropy analysis was performed to identify pleiotropic genes for significant immunophenotype-SLE pairs. A comprehensive gene function analysis was undertaken to explore the mechanisms of immune cells in SLE. By using the instrumental variables extracted from GWAS data, we observed that increased levels of five immune phenotypes were causally associated with SLE risk (FDR < 0.05), that were CD20 on IgD+ CD38- naïve, BAFF-R on IgD+ CD38dim, CD39+ secreting Treg AC, CD14- CD16+ monocyte AC, and HLA DR on CD14+ monocyte. Pairwise gene-based analyses identified a total of 38 pleiotropic genes for 5 significant pairs identified and gene set enrichment analysis revealed the involvement of the identified pleiotropic genes in complex pathways (i.e., systemic lupus erythematosus, an integral component of luminal side of endoplasmic reticulum membrane, C-type lectin receptor signaling pathway and regulation of hormone secretion). This study demonstrates that the immune response influences the progression of SLE in a complex pattern. These findings greatly improve our understanding of the interaction between immune response and SLE risk and also aid in the design of therapeutic strategies from an immunological perspective.


Asunto(s)
Lupus Eritematoso Sistémico , Análisis de la Aleatorización Mendeliana , Humanos , Estudio de Asociación del Genoma Completo , Fenotipo , Transducción de Señal/genética , Lupus Eritematoso Sistémico/genética , Polimorfismo de Nucleótido Simple
10.
Brief Bioinform ; 22(5)2021 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-33822895

RESUMEN

Metagenomics data provide rich information for the detection of foodborne pathogens from food and environmental samples that are mixed with complex background bacteria strains. While pathogen detection from metagenomic sequencing data has become an activity of increasing interest, shotgun sequencing of uncultured food samples typically produces data that contain reads from many different organisms, making accurate strain typing a challenging task. Particularly, as many pathogens may contain a common set of genes that are highly similar to those from normal bacteria in food samples, traditional strain-level abundance profiling approaches do not perform well at detecting pathogens of very low abundance levels. To overcome this limitation, we propose an abundance correction method based on species-specific genomic regions to achieve high sensitivity and high specificity in target pathogen detection at low abundance.


Asunto(s)
Bacterias/genética , Bacterias/patogenicidad , Infecciones Bacterianas/diagnóstico , Enfermedades Transmitidas por los Alimentos/microbiología , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Metagenoma , Metagenómica/métodos , Secuenciación Completa del Genoma/métodos , Infecciones Bacterianas/microbiología , Exactitud de los Datos , Genoma Bacteriano , Humanos , Sensibilidad y Especificidad , Especificidad de la Especie
11.
Europace ; 25(2): 441-449, 2023 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-36504017

RESUMEN

OBJECTIVE: This study sought to assess the effect of ethanol infusion into the vein of Marshall (EIVOM) on the acute success of left pulmonary vein (LPV) isolation in persistent atrial fibrillation (PeAF). METHODS AND RESULTS: A total of 313 patients with drug-resistant PeAF were enrolled (135 in Group 1 and 178 in Group 2). In Group 1, EIVOM was firstly performed, followed by radiofrequency ablation (RFA) including bilateral pulmonary vein isolation (PVI) and linear ablation at roofline, cavotricuspid isthmus, and mitral isthmus (MI). In Group 2, PVI and linear ablations were completed with RFA. First-pass isolation of the LPV was achieved in 119 (88.1%) and 132 (74.2%) patients in Groups 1 and 2, respectively (P = 0.002). The rate of acute pulmonary vein reconnection (PVR) was significantly lower in Group 1 (9.6% vs. 22.5%, P = 0.003). About half of acute PVR occurred in the carina with or without EIVOM. CONCLUSION: EIVOM is effective in achieving a higher first-pass isolation and a lower acute PVR of LPV in PeAF.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Ablación por Radiofrecuencia , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Venas Pulmonares/cirugía , Etanol/efectos adversos , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Resultado del Tratamiento , Recurrencia
12.
Europace ; 25(3): 905-913, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-36563053

RESUMEN

AIMS: To describe the role of left atrial (LA) epicardial conduction and targets of ablation in biatrial tachycardias (BiATs). METHODS AND RESULTS: Consecutive patients with BiAT diagnosed by high-density mapping and appropriate entrainment were enrolled. A systematic review of case reports or series was then performed. Biatrial tachycardia was identified in 20 patients aged 63.5 ± 11.1 years. Among them, eight had LA epicardial conduction, including four via the ligament of Marshall, two via myocardial fibres between the great cardiac vein (GCV) and LA, one via septopulmonary bundle, and one via myocardial fibres between the posterior wall and coronary sinus. Ablation was targeted at the anatomical isthmus in 14, including 5 undergoing vein of Marshall ethanol infusion and 2 undergoing ablation in the GCV. Another six underwent ablation at interatrial connections, including one with septopulmonary bundle at the fossa ovalis and five at the atrial insertions of Bachmann's bundle. After a mean follow-up of 8.7 ± 3.8 months, five patients had recurrence of atrial fibrillation/flutter. Systematic review enrolled 87 patients in previous and the present reports, showing a higher risk of impairment in atrial physiology in those targeting interatrial connections (30.4 vs. 5.0%, P < 0.001) but no significant difference in short- and long-term effectiveness. CONCLUSION: Left atrial epicardial conduction is common in BiATs and affects the ablation strategy. Atrial physiology is a major concern in selecting the target of intervention.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Sistema de Conducción Cardíaco , Resultado del Tratamiento , Taquicardia , Atrios Cardíacos/cirugía , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos
13.
J Appl Microbiol ; 134(7)2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37401152

RESUMEN

AIM: This study aimed to investigate the effects of substituting inorganic iron in the diet of weanling piglets with iron-rich Candida utilis on gut morphology, immunity, barrier, and microbiota. METHODS AND RESULTS: Seventy-two healthy 28-day-old Duroc × Landrace × Yorkshire desexed male weanling piglets were randomly assigned to 2 groups (n = 6), with 6 pens per group and 6 piglets in each pen. The control group was fed a basal diet containing ferrous sulfate (104 mg kg-1 iron), while the experimental group was fed a basal diet supplemented with iron-rich C. utilis (104 mg kg-1 iron). The results show that the growth performance of weanling piglets showed no significantly differences (P > 0.05). Iron-rich C. utilis significantly elevated villus height and decreased crypt depth in the duodenum and jejunum (P < 0.05). Additionally, there was a significant increase in SIgA content, a down-regulated of pro-inflammatory factors expression, and an up-regulated of anti-inflammatory factors expression in the jejunum and ileum of piglets fed iron-rich C. utilis (P < 0.05). The mRNA expression levels of ZO-1, Claudin-1, Occludin, and Mucin2 in the jejunum were significantly increased by iron-rich C. utilis, and were significantly increased ZO-1 and Claudin-1 in the ileum (P < 0.05). The colonic microbiota, however, was not significantly affected by iron-rich C. utilis (P > 0.05). CONCLUSION: Iron-rich C. utilis improved intestinal morphology and structure, as well as intestinal immunity and intestinal barrier function.


Asunto(s)
Suplementos Dietéticos , Hierro , Porcinos , Animales , Masculino , Hierro/metabolismo , Claudina-1/metabolismo , Dieta , Mucosa Intestinal/metabolismo
14.
Pacing Clin Electrophysiol ; 46(2): 190-194, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36069105

RESUMEN

The case highlights an available method to minimize the target volume and reduce the radiation dose by using a temporary catheter, to reduce the long-term risk of radiotherapy for ventricular arrhythmias.


Asunto(s)
Ablación por Catéter , Radiocirugia , Taquicardia Ventricular , Complejos Prematuros Ventriculares , Humanos , Complejos Prematuros Ventriculares/radioterapia , Complejos Prematuros Ventriculares/cirugía , Ventrículos Cardíacos , Resultado del Tratamiento
15.
Pacing Clin Electrophysiol ; 46(1): 20-30, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36401609

RESUMEN

BACKGROUND: Perimitral atrial tachycardia (PMAT) is the most frequent type of iatrogenic atrial tachycardia (AT) after atrial fibrillation (AF) ablation. Vein of Marshall ethanol infusion (EIVOM) is a promising technique in mitral isthmus (MI) ablation. METHODS: A total of 165 patients with PMAT were divided into three groups according to ablation strategies, including RF only group (n = 89), RF-EIVOM group (initial RF ablation with adjunctive EIVOM, n = 28), and EIVOM-RF group (first-step EIVOM with touch-up RF ablation, n = 48). Acute and follow-up procedure outcomes were evaluated. RESULTS: PMAT terminated in 89.9%, 89.3%, and 93.7% of patients in RF only, RF-EIVOM and EIVOM-RF groups, respectively (p = .715), with complete MI block achieved in 80.9%, 89.3%, and 95.8% of patients (EIVOM-RF vs. RF only, p = .012). First-step utilization of EIVOM was associated with a significant shortening of RF ablation time at MI (EIVOM-RF 2.1 ± 1.3 min, RF only 7.9 ± 5.9 min, RF-EIVOM 6.8 ± 5.8 min; p < .001) and a decrease in the proportion of patients need ablation within coronary sinus (CS, EIVOM-RF 14.6%, RF only 61.8%, RF-EIVOM 64.3%; p < .001). After a mean follow-up of 12.1 ± 6.2 months, AF/AT recurred in 39 (43.8%), 6 (21.4%), and 12 (25.0%) patients in RF only, RF-EIVOM, and EIVOM-RF group (RF-EIVOM vs. RF only, p = .026; EIVOM-RF vs. RF only, p = .022). CONCLUSIONS: EIVOM was associated with an enhanced acute MI block rate as well as reduced AF/AT recurrence. First-step utilization of EIVOM promises to significantly simplify the RF ablation process. CONDENSED ABSTRACT: PMAT is the most common type of iatrogenic AT after AF ablation procedures. EIVOM contributed to a higher acute MI block rate and lower arrhythmia recurrence risk during follow-up. First-step utilization of EIVOM significantly reduced the need for radiofrequency ablation at MI and inside CS with the advantage of creating a homogenous, transmural lesion and eliminating epicardial connections.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Taquicardia Supraventricular , Humanos , Etanol , Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Enfermedad Iatrogénica , Resultado del Tratamiento , Recurrencia
16.
Support Care Cancer ; 31(5): 303, 2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-37099077

RESUMEN

PURPOSE: The experiences of patients with diffuse large B-cell lymphoma (DLBCL) treated with chimeric antigen receptor (CAR) T-cell therapy have received little attention. This study aimed to explore the treatment experiences of patients with relapsed or refractory (R/R) B-cell lymphoma during CAR T-cell therapy in China. METHODS: This descriptive qualitative study was conducted using face-to-face semi-structured interviews with 21 DLBCL patients 0-2 years after CAR-T infusion. Two researchers independently coded the interviews in MAXQDA 2022, and the original data were analyzed by conventional content analysis. RESULTS: Four themes emerged from the transcripts: (1) physiological distress, (2) functional impacts, (3) psychological experience, and (4) support requirement. Participants expressed 29 short-term or long-term symptoms related to their disease and treatment, influencing their daily life and function in a social setting. The participants expressed different negative emotions, polarized expectations about efficacy, and over-reliance on authoritative medical care. Their major concerns and hopes were achieving life goals, being treated with respect, obtaining more information about CAR T-cell therapy, and receiving government financial sponsorship. CONCLUSIONS: The patients experienced short-term and long-term symptoms of physical distress. Patients who have experienced failure in CAR T-cell therapy also experience strong negative emotions, such as dependency and guilt. They also require authentic spiritual and financial information that is authentic. Our study may guide the development of standardized and comprehensive nursing care for R/R DLBCL patients undergoing CAR T-cell therapy in China.


Asunto(s)
Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Humanos , Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso/terapia , China , Tratamiento Basado en Trasplante de Células y Tejidos
17.
Int J Clin Pharmacol Ther ; 61(10): 445-454, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37548455

RESUMEN

OBJECTIVE: The aim of this study was to identify and characterize all European Medicines Agency (EMA) approvals derived from adaptive designs in clinical trials and to provide an update of the current status of these drugs. MATERIALS AND METHODS: Relevant files were identified in the EMA database for annual reports for the period between 2008 and 2020 using a list of suitable keywords related to adaptive designs. We recorded trial characteristics from drug approvals and used Fisher exact test to compare the characteristics. RESULTS: A total of 1,054 EMA approvals were identified, and the percentage of EMA approvals planned with adaptive trial designs increased from 1.85% in the period 2008 - 2012 to 6.19% in between 2017 - 2020. A total of 41 approvals were identified among 91 original EMA files that contained adaptive designs. The types of adaptive designs used in clinical trials increased after 2017 where the most common type used was the most common (17/41). Most approvals (32/41) comprised pivotal trials, and most assessments had not been accelerated (38/41). Of 32 confirmatory trials planned with adaptive designs, the proportion of those with additional monitoring (AM) increased significantly (p < 0.0001) from 0% in the 2008 - 2012 period to 90.48% in the 2017 - 2020 period. The percentage of approved antitumor drugs in approved drugs in ongoing clinical trials was 82.35%, compared to 20.83% in trials that were completed (p = 0.0001). The proportion of drug approved but where clinical trials were still ongoing in companies requiring post-authorization safety studies (PASSs) or post-authorization efficacy studies (PAESs) or who were granted conditional marketing authorization (CMA) significantly differed from the group of drugs approved where clinical trials were completed (p = 0.0230). CONCLUSION: A trend showing an increased number of EMA approvals related to adaptive designs was observed for the period from 2008 to 2020. Different types of adaptive trial designs could be encouraged for the designation of clinical trials, especially for antitumor drugs; meanwhile, more stringent monitoring regulations seemed to be conducted for ongoing trials of antitumor drugs with adaptive design.


Asunto(s)
Antineoplásicos , Ensayos Clínicos como Asunto , Proyectos de Investigación , Humanos , Antineoplásicos/uso terapéutico , Aprobación de Drogas , Europa (Continente)
18.
BMC Public Health ; 23(1): 2257, 2023 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-37974168

RESUMEN

BACKGROUND: The growing prevalence of smartphone use among college students in China has led to health concerns, including De Quervain's Tenosynovitis (DQT). However, the specific smartphone usage behaviors contributing to DQT remain poorly understood. This study aimed to explore the relationship between smartphone usage behaviors and DQT in college students. METHODS: A cross-sectional study was conducted with 937 students from various majors in Guangxi between September 2021 and April 2022. Participants completed an online questionnaire assessing smartphone usage behaviors and their association with DQT. The Finkelstein test was employed to diagnose DQT. RESULTS: Over half of the college students (52%) tested positive for DQT via Finkelstein's test. Higher levels of smartphone usage time (6-8 h/day: OR = 4.454, 95%CI:1.662-12.229; ≥8 h/day: OR = 4.521, 95%CI:1.596-12.811), phone games (OR = 1.997, 95%CI:1.312-3.040), social media (OR = 2.263, 95%CI:1.795-3.833), and leisure activities (OR = 1.679, 95%CI:1.140-2.475) were significantly associated with an increased risk of DQT. Two specific gestures (Bilateral thumbs, BT: OR = 1.900, 95%CI:1.281-2.817; Bilateral thumbs-horizontal screen, BT-HS: OR = 1.872, 95%CI:1.244-2.818) and two screen sizes (5.0-5.5inch: OR = 2.064, 95%CI:1.108-3.846; 6.0-6.5inch: OR = 2.413, 95%CI:1.125-4.083) also exhibited a higher risk of DQT. Bilateral DQT was observed, with Gesture-BT identified as the primary risk factor. CONCLUSION: Our findings suggest that increased smartphone usage time, phone games, social media, and leisure activities elevate the risk of DQT among college students. Furthermore, two specific gestures and two screen sizes were also linked to a heightened DQT risk. To mitigate DQT development, college students should reduce smartphone usage time and adopt appropriate gestures.


Asunto(s)
Enfermedad de De Quervain , Tenosinovitis , Humanos , Tenosinovitis/complicaciones , Enfermedad de De Quervain/complicaciones , Enfermedad de De Quervain/diagnóstico , Enfermedad de De Quervain/epidemiología , Teléfono Inteligente , Estudios Transversales , China/epidemiología , Estudiantes
19.
World J Surg Oncol ; 21(1): 307, 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37752577

RESUMEN

BACKGROUND: Frailty is considered a characteristic manifestation of physiological decline in multiple organ systems, which significantly increases the vulnerability of elderly individuals with colorectal cancer (CRC) and is associated with a poor prognosis. While studies have demonstrated that the 11-factor Modified Frailty Index (mFI-11) can effectively predict adverse outcomes following radical resection of CRC, there is a lack of research on the applicability of the 5-factor Modified Frailty Index (mFI-5) within this patient population. METHODS: In this retrospective analysis, we examined a cohort of CRC patients aged 65 years and above who had undergone radical resection. For each patient, we calculated their mFI-5 score, considering a score of ≥ 2 as an indication of frailty. We conducted univariate and multivariate analyses to assess the association between the mFI-5 and adverse outcomes as well as postoperative complications. RESULTS: Patients with an mFI-5 score ≥ 2 exhibited a significantly higher incidence of serious postoperative complications (53% vs. 30%; P = 0.001) and experienced a longer hospital stay [19.00 (15.00-24.50) vs. 17.00 (14.00-20.00); P < 0.05]. Notably, an mFI-5 score greater than 2 emerged as an independent risk factor for severe postoperative complications (odds ratio: 2.297; 95% confidence interval: 1.216 to 4.339; P = 0.01). Furthermore, the mFI-5 score displayed predictive capabilities for severe postoperative complications with an area under the receiver operating characteristic (ROC) curve of 0.629 (95% confidence interval: 0.551 to 0.707; P < 0.05). CONCLUSION: The mFI-5 demonstrates a high level of sensitivity in predicting serious complications, prolonged hospital stays, and mortality following radical resection of colorectal carcinoma. As a practical clinical assessment tool, the mFI-5 enables the identification of high-risk patients and facilitates preoperative optimization.


Asunto(s)
Neoplasias Colorrectales , Fragilidad , Anciano , Humanos , Fragilidad/complicaciones , Medición de Riesgo , Estudios Retrospectivos , Factores de Riesgo , Complicaciones Posoperatorias/epidemiología , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/complicaciones
20.
Pak J Pharm Sci ; 36(4(Special)): 1281-1290, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37606017

RESUMEN

A new method for the determination of rebamipide in human heparin sodium plasma by LC-MS was established and its methodology was validated. In this method, protein precipitation method was used to pretreat the samples and the rebamipide-d4 isotope of rebamipide was used as the internal standard. In the multi reaction monitoring mode, the electrospray ion source was used as the ionization technolog and LC-MS was used for detection and analysis. The liquid chromatographic conditions were: 00B-4605-AN (Kinetex® XB-C18 100A 50mm × 2.1mm, 5µm); mobile phase A: 0.1% FA and 1 mM NH4FA aqueous solution, mobile phase B: 0.1% FA and 1mM NH4FA 90% ACN solution, flow rate: 0.300mL/min, injection volume: 10uL, column temperature: 30oC, collection time: 3 min, injector temperature control: 5oC. The retention time of rebamipide and rebamipide-d4 were 1.32min and 1.31min, respectively. The lower limit of quantification was 1ng/mL and the calibration map of rebamipide in the concentration range of 1 to 800ng/mL was linear (R2 >0.990, n=11). The CV% values of the inter and intra batch precision of the method were both less than 15.0%. This method has been successfully applied to pharmacokinetic studies to evaluate the main pharmacokinetic parameters of rebamipide.


Asunto(s)
Heparina , Espectrometría de Masas en Tándem , Humanos , Calibración , Cromatografía Liquida
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA