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Surface Enhanced Raman Scattering (SERS) has been extensively utilized in therapeutic drug monitoring (TDM) due to its rapid detection speed, high sensitivity and straightforward sample pretreatment. In this study, Au/AgNPs were obtained through the reduction of AgNO3 on the surface of AuNPs. Subsequently, Au/AgNPs were embedded into the tetrahedral lattice of ZIF-8 MOFs, resulting in the formation of Au/Ag@ZIF-8 nanocomposites. The Au/Ag@ZIF-8 nanocomposites exhibit a robust electromagnetic enhancement of Au/Ag bimetallic nanoparticles and a considerable adsorption capacity of ZIF-8 MOFs. This enables the pre-enrichment of target molecules in the vicinity of the electromagnetic field of the Au/AgNPs, thereby enhancing the sensitivity of SERS detection. The SERS substrate also exhibits high stability and reproducibility, as well as molecular sieving effects, due to the fact that Au/AgNPs are embedded into the tetrahedral lattice of ZIF-8. A TDM method for tacrolimus (FK506) in human serum was developed by using Au/Ag@ZIF-8 nanocomposites as solid phase extraction (SPE) adsorbent and SERS substrates. The results showed that under the optimized conditions, tacrolimus exhibited satisfactory linearity within the concentration range of 10-5-10-11 mol L-1, with a correlation coefficient (R2) of 0.9944, and the limit of detection (LOD) was as low as 6.4 pg mL-1. The recoveries were observed to range between 92 % and 105 %, with an RSD of below 8 %. The method is highly sensitive, exhibiting a sensitivity that is 3-6 orders of magnitude higher than that of existing analytical techniques. It has the potential to be applied in a clinical setting to biological samples.
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Monitoreo de Drogas , Oro , Estructuras Metalorgánicas , Nanocompuestos , Plata , Extracción en Fase Sólida , Espectrometría Raman , Tacrolimus , Humanos , Plata/química , Oro/química , Espectrometría Raman/métodos , Extracción en Fase Sólida/métodos , Nanocompuestos/química , Tacrolimus/sangre , Tacrolimus/química , Adsorción , Monitoreo de Drogas/métodos , Estructuras Metalorgánicas/química , Límite de Detección , Nanopartículas del Metal/química , Zeolitas/química , ImidazolesRESUMEN
Introduction: In the field of agriculture, automated harvesting of Camellia oleifera fruit has become an important research area. However, accurately detecting Camellia oleifera fruit in a natural environment is a challenging task. The task of accurately detecting Camellia oleifera fruit in natural environments is complex due to factors such as shadows, which can impede the performance of traditional detection techniques, highlighting the need for more robust methods. Methods: To overcome these challenges, we propose an efficient deep learning method called YOLO-CFruit, which is specifically designed to accurately detect Camellia oleifera fruits in challenging natural environments. First, we collected images of Camellia oleifera fruits and created a dataset, and then used a data enhancement method to further enhance the diversity of the dataset. Our YOLO-CFruit model combines a CBAM module for identifying regions of interest in landscapes with Camellia oleifera fruit and a CSP module with Transformer for capturing global information. In addition, we improve YOLOCFruit by replacing the CIoU Loss with the EIoU Loss in the original YOLOv5. Results: By testing the training network, we find that the method performs well, achieving an average precision of 98.2%, a recall of 94.5%, an accuracy of 98%, an F1 score of 96.2, and a frame rate of 19.02 ms. The experimental results show that our method improves the average precision by 1.2% and achieves the highest accuracy and higher F1 score among all state-of-the-art networks compared to the conventional YOLOv5s network. Discussion: The robust performance of YOLO-CFruit under different real-world conditions, including different light and shading scenarios, signifies its high reliability and lays a solid foundation for the development of automated picking devices.
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Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of a number of patients with advanced cancer, and while this has resulted in increased survival times, it has also led to the emergence of novel immune-related adverse events (irAEs). In individuals with advanced cancer, sarcopenia is a significant symptom of cachexia and is linked to poor nutritional status and increased mortality. The present study aimed to evaluate sarcopenia and other risk variables that can affect the emergence of irAEs in patients with lung cancer. Methods: A single-center retrospective analysis of 129 patients with advanced lung cancer treated with programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) checkpoint inhibitors was conducted from August 2020 to August 2022. Data on baseline characteristics and adverse events of participants were collected. Computed tomography was used to determine the skeletal muscle index at the third lumbar vertebra (L3-SMI) and whether sarcopenia is present. Results: The median age of all participants was 60 years old (range, 52-66 years), with men accounting for 68.9% of the total patient cohort. The present study showed that 44 (34%) participants presented with any degree of irAEs, and 79 (61.2%) patients presented with sarcopenia. There were no statistically significant differences in baseline characteristics, such as age and sex, between patients who presented with irAEs and those without irAEs. Using logistic regression analysis, individuals with sarcopenia were 2.635-times more likely to experience any grade of irAEs than those without sarcopenia. Discussion: irAEs are prevalent side effects of PD-1/PD-L1 inhibitor therapy for patients with cancer. By diagnosing and treating sarcopenia early, it is possible to lower the potential risk of irAEs in patients with advanced cancer. Furthermore, sarcopenia can be utilized as a predictor of irAEs.
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Objective: This study aimed to discover micro-ribonucleic acids (microRNAs) involved in the degeneration of cartilage endplates through next-generation sequencing and lay the foundation for further research. Methods: The cartilage endplate was obtained from patients who underwent interbody fusion surgery at the Department of Spine Surgery, Shanghai East Hospital Affiliated to Tongji University, from 1 January 2020 to 1 January 2023. Total RNA was extracted from the cartilage endplate tissue. Discover differential genes through NGS. To annotate gene functions, all target genes were aligned against the Kyoto Encyclopedia of Genes (KEGG) and Gene Ontology (GO) databases. The GO enrichment and KEGG enrichment analyses of target genes were performed using phyper, a function of R. The p-value was corrected using the Bonferroni method, and a corrected p-value of ≤0.05 was taken as the threshold. GO terms or KEGG terms fulfilling this condition were defined as significantly enriched terms. The screened miRNAs and their target protein were verified in vitro using quantitative polymerase chain reaction (qPCR) and Western blotting (WB). Results: RNA was extracted from normal and degenerated cartilage endplate tissues for NGS. Eight downregulated differentially expressed genes (DEGs) and 22 upregulated DEGs were found. The KEGG pathway analysis of these target genes revealed that differential microRNAs and target genes were enriched in different signaling pathways, and the regulated signaling pathways were mainly mitochondrial autophagy and autophagy. The qPCR results demonstrated a significant upregulation of miR-25-3p and miR-345-5p in degenerative cartilage endplate tissues (p ≤ 0.001). Western blot analysis revealed that BRD4 exhibited a marked increase in protein expression levels in degenerative cartilage endplate tissues (p ≤ 0.0001), while BECN1 showed a significant decrease in protein expression levels within these samples (p ≤ 0.0001). Conclusion: We found that DEG hsa-miR-25-3p and hsa-miR-345-5p can be used as diagnostic and therapeutic targets for IDD. The significant target proteins of miR-25-3p and miR-345-5p were BRD4 and BECN1, respectively.
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Al-doped Ga2O3microbelts with widths ranging from 20 to 154µm and lengths up to 2 mm were grown using carbothermal reduction. Based on these ultra-wide microbelts, single-microbelt (37µm wide) and double-microbelts(38µm/42µm wide) metal-semiconductor-metal photoconductive ultraviolet (UV) detectors PDs were fabricated and their optoelectronic performances were investigated at Vacuum-UV (VUV) wavelengths of 185 nm. Under irradiation of 185 nm, the Al-doped Ga2O3PD has a very-high photocurrent (Iph) of 192.07µA and extremely low dark current (Id) of 156 fA at 10 V, and presents a ultra-high light-to-dark current ratio of 1.23 × 109. The responsivity (R), external quantum efficiency (EQE), and detectivity (D*) of the double-microbelts detector device were 1920 A W-1, 9.36 × 105%, and 8.6 × 1016Jones, respectively. Since the bandgap of the Al-doped microbelts becomes wider, and the fabricated detector has weaker sensitivity to radiation in the 254/365 nm wavelengths. Compared with the 254 nm and 365 nm UV cases, the devices under 185 nm VUV show the excellent high selectivity ratios of 1.47 × 106and 1.7× 107, respectively. This paper should provide a new insight on the VUV photodetectors utilizing Ga2O3microbelts.
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A simple mono/dialkylation of acrylamide derivatives was achieved, affording diverse mono/dialkylated benzo[4,5]imidazo[2,1-a]isoquinolines or polycyclic coumarins with good substrate scope. This system used common peroxides as alkylating reagents. Meanwhile, a series of scaled-up reactions and mechanistic explorations well demonstrated the application and reaction process of this cascade system.
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The use of harmful halogenated or aromatic solvents such as chloroform (CF), chlorobenzene (CB), and o-xylene (o-XY) is one of the greatest barriers to the industrial-scale manufacturing of high-performance organic solar cells (OSCs). Therefore, it is necessary to eliminate the effects of these solvents to ensure practical feasibility of OSCs. We found that the anthracene-terminated polymer donor and small-molecule acceptor BO-4Cl had good solubility in 3-methylthiophene (3-MeT). There were no toxicity labels in the SDS and exposure control limits for 3-MeT. An overall power conversion efficiency of 16.87% was achieved by using 3-MeT as the solvent for solar cell fabrication, which was higher than that of the cells made from CF (16.18%) and o-XY (15.69%). The best OSC based on PM6:D18:L8-BO and fabricated with 3-MeT exhibited a high PCE of 18.13%, which is one of the highest values for cells fabricated from halogen-free solvents. These results indicate that 3-MeT is an eco-friendly and low-toxicity solvent for the sustainable fabrication of the OSC active layer.
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The surface of calcined kaolinite particles underwent chemical modification using Vinyltriethoxysilane (VTMS) and 3-mercaptopropionic acid (3-MPA). The grafting ratio of VTMS on the calcined kaolinite surface was adjusted by varying its quantity. FT-IR analysis revealed the initial grafting of VTMS onto the kaolinite surface, resulting in the formation of a C=C reactive site on the surface. Subsequently, an olefin click reaction with 3-MPA occurred, leading to the effective grafting of 3-MPA onto the kaolinite surface and the formation of an efficient coating. Thermal analysis indicated that the optimal grafting level was achieved at a modifier content V:K ratio of 0.5. The estimated grafting ratio of the modifier on the kaolinite surface was approximately 40% when V:K was 0.5. Water contact angle and dispersion experiments demonstrated that the surface properties of kaolinite were effectively controlled by this modification approach. At V:K = 0.3, the modified kaolinite particles exhibited good dispersion in both polar and non-polar solvents. In polar solvents, the average particle size of modified kaolinite was below 1100 nm, while in non-polar solvents, it did not exceed 5000 nm. Considering all aspects, a V:K ratio of 0.3 is recommended. Further investigation into the impact of adding 3-MPA on the surface properties of modified kaolinite particles based on V:K = 0.3 revealed that the hydrophilicity of the modified particles could be enhanced. However, it is advised to keep the maximum M:V ratio (3-MPA to kaolinite) at 1.0.
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BACKGROUND: Obesity is often associated with impaired immune responses, including enlarged spleen, increased inflammation, and impaired T-cell-mediated function, which may lead to increased susceptibility to infections. Bioactive compounds found in various fruits and vegetables (F&V) have been shown to have strong anti-inflammatory effects. However, few prospective studies have examined the effects of F&V on preventing obesity-associated dysregulation of immune and inflammatory responses. OBJECTIVE: The objective of this was to determine the impact of different levels of a mixture of F&V incorporated in a high-fat diet (HFD) on immune function changes in a diet-induced obesity animal model. METHODS: Six-wk-old male C57BL/6J mice were randomly assigned to 1 of 5 groups (n = 12/group): matched low-fat control (LF, 10% kcal fat) or HFD (45% kcal fat) supplemented with 0%, 5%, 10%, or 15% (wt/wt) freeze-dried powder of the most consumed F&V (human equivalent of 0, 3, 5-7, 8-9 servings/d, respectively) for 20 wk. Spleen weight was recorded, and the immunophenotype of splenocytes was evaluated by flow cytometry. Ex vivo splenic lymphocyte proliferation was assessed by thymidine incorporation and serum cytokines concentrations were measured by Meso Scale Discovery. RESULTS: Mice fed the HFD exhibited significantly higher spleen weight, decreased splenic CD8+ lymphocytes, suppressed T lymphocyte proliferation, and reduced serum IL-1ß and IFN-γ concentrations compared with those fed the LF diet. Feeding mice with the HFD supplemented with 10% or 15% F&V restored HFD-associated changes of these affected biomarkers compared with those fed HFD only. Furthermore, a significant correlation was found between immunologic markers and F&V level. CONCLUSIONS: These results suggest that increased consumption of F&V has beneficial effects in preventing HFD-associated dysregulation of immune function.
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Dieta Alta en Grasa , Frutas , Inflamación , Ratones Endogámicos C57BL , Obesidad , Verduras , Animales , Masculino , Obesidad/prevención & control , Ratones , Inflamación/prevención & control , Bazo , Ratones Obesos , Citocinas/metabolismo , Citocinas/sangreRESUMEN
The ß-glucosidases known to improve tea aroma are all mesothermal enzymes, limiting their use under brewing conditions. Based on the properties analysis and molecular docking, the thermostable ß-glucosidase (TPG) from Thermotoga petrophlia showed potential to enhance tea aroma. Treatment by recombinant TPG at 90 °C, the floral, sweet and grassy notes of instant Oolong tea were increased, while the roasted, caramel and woody notes were decreased. The improved floral, sweet and grassy notes were related to increase releasing of benzyl alcohol (floral), geraniol (floral), (Z)-3-hexen-1-ol (grassy), benzaldehyde (sweet) and 1-hexanol (grassy) by TPG hydrolyzing of (Z)-3-hexenyl-ß-D-glucopyranoside, hexanyl-ß-D-glucopyranoside (HGP), benzyl-ß-D-glucopyranoside, prunasin and geranyl-ß-D-glucopyranoside (GGP), respectively. Although the catalytic efficiency of TGP to GGP was about twice that to HGP, HPG was more competitive than GGP when they mixed. Combined with microstructure analysis, the structure-function relationship of TPG-influencing tea aroma were understood. This study provided the method of how to mining new function of characterized ß-glucosidases, as well as a theoretical basis for the development of new tea products.
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Estabilidad de Enzimas , Odorantes , Té , beta-Glucosidasa , beta-Glucosidasa/química , beta-Glucosidasa/metabolismo , Té/química , Odorantes/análisis , Camellia sinensis/química , Camellia sinensis/enzimología , Simulación del Acoplamiento Molecular , Aromatizantes/química , Aromatizantes/metabolismo , Compuestos Orgánicos Volátiles/química , Compuestos Orgánicos Volátiles/metabolismo , Calor , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismoRESUMEN
In this study, we aimed to explore the hypoglycemic effects of a hydrolysate on Takifugu bimaculatus skin (TBSH). The effect of the dipeptidyl peptidase-IV (DPP-IV) inhibitory activities from different TBSH fractions was investigated on basic indexes, gut hormones, blood lipid indexes, viscera, and the gut microbiota and its metabolites in rats with type 2 diabetes mellitus (T2DM). The results showed that the <1 kDa peptide fraction from TBSH (TBP) exhibited a more potent DPP-IV inhibitory effect (IC50 = 0.45 ± 0.01 mg/mL). T2DM rats were induced with streptozocin, followed by the administration of TBP. The 200 mg/kg TBP mitigated weight loss, lowered fasting blood glucose levels, and increased insulin secretion by 20.47%, 25.23%, and 34.55%, respectively, rectified irregular hormonal fluctuations, lipid metabolism, and tissue injuries, and effectively remedied gut microbiota imbalance. In conclusion, TBP exerts a hypoglycemic effect in rats with T2DM. This study offers the potential to develop nutritional supplements to treat T2DM and further promote the high-value utilization of processing byproducts from T. bimaculatus. It will provide information for developing nutritional supplements to treat T2DM and further promote the high-value utilization of processing byproducts from T. bimaculatus.
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Glucemia , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Hiperglucemia , Hipoglucemiantes , Péptidos , Piel , Takifugu , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ratas , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Hipoglucemiantes/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Piel/efectos de los fármacos , Piel/metabolismo , Hiperglucemia/tratamiento farmacológico , Glucemia/efectos de los fármacos , Péptidos/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Metaboloma/efectos de los fármacos , Ratas Sprague-Dawley , Insulina/metabolismo , Insulina/sangreRESUMEN
BACKGROUND: Osteoarthritis (OA) is a global public health problem, and limited information is available on the effects of Cd on OA. The purpose of this study is to explore the relationship between Cd and OA. METHOD: Weighted multivariable logistic regression model, trend test, restricted cubic spline, and stratified analysis were used to study the association between BCd and OA. RESULTS: In the two regression models of weighted multivariable logistic regression analysis, the correlation between BCd and OA was positive. Compared with the lowest quartile of BCd exposure, the highest quartile had a 2.03-fold (95% confidence interval, 1.67 to 2.47), displaying a dose-response relationship (P for trend <0.00001). The restrictive cubic spline shows a positive linear relationship between BCd and OA. CONCLUSION: There was a positive linear relationship between BCd and OA and a dose-response relationship.
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Cadmio , Encuestas Nutricionales , Osteoartritis , Humanos , Masculino , Femenino , Osteoartritis/sangre , Osteoartritis/epidemiología , Cadmio/sangre , Persona de Mediana Edad , Estados Unidos/epidemiología , Adulto , Anciano , Modelos Logísticos , Estudios Transversales , Exposición a Riesgos Ambientales/efectos adversosRESUMEN
BACKGROUND: Sleep disturbances are highly prevalent in oncology and often exacerbate symptoms, leading to reduced quality of life, which in turn may further affect the tolerability and efficacy of oncological treatments. Sleep disturbance and cancer have an intimate and complicated relationship, and may be a negative predictor of cancer treatment. The present study aimed to characterize the relationship between sleep disturbance and immune checkpoint inhibitor (ICI) therapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Data from 171 patients with advanced NSCLC, who underwent ICI treatment between December 2020 and October 2022, were analysed in our prospective study. Sleep disturbances were evaluated according to the Pittsburgh Sleep Quality Index (PSQI), with a cut-off value of 5, to investigate the impact of sleep disturbance on the survival of patients with NSCLC and the efficacy of ICI treatment. RESULTS: The median progression-free survival (PFS) was10.4 months (9 5% confidence interval [CI]:9.84-10.97). Univariate and multivariate analyses revealed that sleep disturbance and depressive symptom predicted worse prognosis with shortened PFS. Patients who experienced sleep disturbance exhibited a significant reduction in PFS (9.2 vs. 11.8 months; HR: 1.83 [9 5% CI 1.27-2.6 5]; p = 0.001), as did those with depressive states (HR 1.5 5 [9 5% CI 1.06-2.28]; p = 0.02 5). Additionally, patients with sleep disturbance and depressive symptoms exhibited significantly lower objective response rates and disease control rates. CONCLUSION: Sleep disturbance could be a factor for prognosis in patients with advanced NSCLC undergoing first- or second-line treatment with ICIs, including shorter PFS and reduced efficacy.
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Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Trastornos del Sueño-Vigilia , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Masculino , Femenino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/complicaciones , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Pronóstico , Adulto , Depresión , Calidad de Vida , Supervivencia sin Progresión , Anciano de 80 o más AñosRESUMEN
The present study focuses on the role of family support to young adult children during COVID-19 in ameliorating the negative financial impact of the pandemic. Guided by the Conservation of Resources (COR) Theory of stress and coping, we conceptualize the negative financial impact due to COVID-19 as a source of financial stress that would be associated with lower levels of both financial wellbeing and positive outlook of young adults. We rely on data collected from a multinational sample of young adults (ages 18-30) from six countries (China, Italy, Lithuania, Portugal, Slovenia, US; N = 2102) over a 3-month period (July 2020-September 2020). We tested the potential effects of two types of support (i.e., parental financial support and family emotional support) using path analysis. While we find a consistent positive association between family emotional support and both financial wellbeing and positive outlook, we also find a consistent negative association between parental financial support and financial wellbeing, and a nonsignificant or negative association (Lithuania only) with a positive outlook. The significant interaction between COVID-19 financial impact and family emotional support on young adults' positive outlook reveals that the benefit of family emotional support is more evident when the negative financial impact is low or moderate. We discuss the implications of these findings in assisting young adults to cope with financial disruptions.
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OBJECTIVES: This study aimed to investigate the clinical relevance of antineutrophil cytoplasmic antibody (ANCA) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: Detailed clinical records of rheumatoid arthritis (RA) patients who underwent ANCA screening tests were collected. ANCA measurements were determined by indirect immunofluorescence assay (IIF) and enzyme-linked immunosorbent assay (ELISA). Clinical characteristics were compared between ANCA-positive and ANCA-negative groups, and multivariable logistic models were used to evaluate the independent association of ANCA with ILD in RA patients. RESULTS: The prevalence of ANCA by IIF was significantly higher in RA-ILD patients compared to those with RA without ILD (31.7 % vs. 19.5 %, p < 0.001). RA-ILD patients positive for ANCA exhibited elevated levels of inflammatory markers and greater disease activity, and showed more severe impairment of lung function compared to ANCA-negative RA-ILD patients. Multivariable logistic regression analysis revealed an independent association of ANCA, especially pANCA, with RA-ILD. ANCA specificities for BPI, elastase, and cathepsin-G were found in 15.6 % of RA-ILD patients; the specificities for most others remain unknown. CONCLUSIONS: The findings suggest a potential role for ANCA/pANCA in stratifying the risk of RA and provide supplementary information to the existing clinically available assays. This additional information may be valuable in identifying RA patients who require further investigations for RA-ILD, such as high-resolution computed tomography (HRCT). These results emphasize the potential clinical relevance of ANCA in the context of RA-ILD.
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Anticuerpos Anticitoplasma de Neutrófilos , Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Humanos , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/complicaciones , Artritis Reumatoide/complicaciones , Artritis Reumatoide/inmunología , Artritis Reumatoide/sangre , Masculino , Femenino , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Persona de Mediana Edad , Factores de Riesgo , AncianoRESUMEN
A drug-drug interaction (DDI) trial of cytochrome P450 3A (CYP3A) is a necessary part of early-phase trials of drugs mainly metabolized by this enzyme, but CYP3A DDI clinical trials do not have a standard design, especially for Chinese people. We aimed to offer specific recommendations for CYP3A DDI clinical trial design. This was an open, three-cycle, self-controlled study. Healthy subjects were given different administration strategies of CYP3A4 perpetrators. In each cycle, blood samples were collected before and within 24 h after the administration of midazolam, the CYP3A indicator substrate. The plasma concentrations of midazolam and 1-hydroxymidazolam was obtained using liquid chromatography tandem mass spectrometry assay. For CYP3A inhibition, itraconazole exposure with a loading dose could increase the exposure of midazolam by 3.21-fold based on maximum plasma concentration (Cmax), 8.37-fold based on area under the curve Pharmacology Research & Perspectives for review only from zero to the time point (AUC0-t), and 11.22-fold based on area under the curve from zero to infinity (AUC0-∞). The data were similar for itraconazole pretreatment without a loading dose. For CYP3A induction, the exposure of rifampin for 7 days decreased the plasma concentration of midazolam ~0.27-fold based on Cmax, ~0.18-fold based on AUC0-t, and ~0.18-fold based on AUC0-∞. Midazolam exposure did not significantly change when the pretreatment of rifampin increased to 14 days. This study showed that itraconazole pretreatment for 3 days without a loading dose was enough for CYP3A inhibition, and pretreatment with rifampin for 7 days could induce near-maximal CYP3A levels.
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Inhibidores del Citocromo P-450 CYP3A , Citocromo P-450 CYP3A , Interacciones Farmacológicas , Itraconazol , Midazolam , Humanos , Midazolam/farmacocinética , Midazolam/administración & dosificación , Midazolam/sangre , Midazolam/análogos & derivados , Itraconazol/farmacología , Itraconazol/administración & dosificación , Citocromo P-450 CYP3A/metabolismo , Masculino , Adulto , Inhibidores del Citocromo P-450 CYP3A/farmacología , Inhibidores del Citocromo P-450 CYP3A/administración & dosificación , Adulto Joven , Rifampin/farmacología , Rifampin/administración & dosificación , Voluntarios Sanos , Femenino , Inductores del Citocromo P-450 CYP3A/farmacología , Área Bajo la Curva , Proyectos de Investigación , Ensayos Clínicos como Asunto , Pueblos del Este de AsiaRESUMEN
An H2O/heating or [bis(trifluoroacetoxy)iodo]benzene promoted radical cascade nitro/azide cyclization of 1-acryloyl-2-cyanoindoles with tert-butyl nitrite/azidotrimethylsilane was accomplished, which offered a series of nitro/azide-featuring pyrrolo[1,2-a]indolediones in good yields. Meanwhile, some scale-up experiments and substituent transformations were performed to test the synthetic value. In addition, the corresponding radical intermediates were successfully detected by HRMS to support the possible reaction pathway.
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PURPOSE: Adolescent and young adult (AYA) cancer patients, aged between 15 to 39 years old, suffer from long-term psychological distress, confronting low self-efficacy and various psychological problems. This study constructs a group online-based peer support intervention combined with offline activities to explore its impact on the psychological distress of AYA cancer patients. METHODS: A randomized, two-arm clinical trial was conducted in which 90 AYA cancer patients were recruited. The control group (N = 45) received conventional psychological care and treatment, and the experimental group (N = 45) received 8 weeks of an online peer support intervention. Outcome measures included psychological distress (Distress Thermometer, DT), anxiety and depression (Hospital Anxiety and Depression Scale, HADS), perceived peer support (Cancer Peer Support Scales, CaPSS), and readiness for return to work (Readiness to Return-To-Work Scale, RRTW). RESULTS: Eight-week peer support intervention was effective in improving psychological distress, anxiety, and depressive symptoms in the experimental group with statistically significant differences (P < 0.05). Time affected psychological distress, anxiety, and depressive symptoms in AYA cancer patients (P < 0.05), and there was an interaction with intervention factors (P < 0.05). The intervention has a positive effect on relieving the psychological status of AYA cancer patients. For readiness for return to work, the experimental group was in the preparation for the action-behavioral stage immediately, 1 month and 3 months after the end of the intervention (P < 0.01), supporting AYA cancer patients who have not returned to work to maintain optimal return-to-work readiness. CONCLUSIONS: The group online-based peer support intervention is popular and has good scientificity, effectiveness, and practical significance for AYA cancer patients. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov. (ChiCTR2100053091, registered on 10 November 2021).
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Neoplasias , Grupo Paritario , Distrés Psicológico , Apoyo Social , Humanos , Adolescente , Femenino , Masculino , Adulto Joven , Adulto , Neoplasias/psicología , Neoplasias/terapia , Depresión/terapia , Depresión/etiología , Depresión/psicología , Ansiedad/etiología , Ansiedad/terapia , Estrés Psicológico/etiología , Estrés Psicológico/terapia , Intervención basada en la InternetRESUMEN
Shift work is a recognized work pattern for nurses worldwide. The disruption of shift workers' biological clocks usually leads to sleep disorders and affects their awareness at work. Eveningness and occupational stress might be effective in causing burnout syndrome. Therefore, this study aimed to evaluate the chronotype, job burnout and perceived stress among Chinese tertiary hospital nurses, and understand the predictors of circadian rhythm in this group. Between July and September 2020, 23 hospitals were randomly selected from 113 tertiary hospitals in Hunan Province. Twenty-five percent of the nurses working in each hospital were targeted for selection. 28.1% and 17.6% of nurses reported eveningness type and morningness type, respectively. The scores for emotional exhaustion, depersonalization, and perceived stress of eveningness nurses were higher than those of morningness counterparts. Eveningness nurses also reported a lower sense of personal accomplishment. Risk factors of eveningness included being under 30 years old, never exercising, having the stressors of late-night shifts and career development, higher levels of emotional exhaustion, sleep latency, sleep duration, and hypnotic use. Shifts may be unavoidable for nurses, nevertheless, understanding the predictors and related factors of chronotype for nurses is necessary for nursing educators and managers to develop a reasonable shift system and appropriate measures to assist nurses in adjusting their work.