Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 319
Filtrar
1.
Heliyon ; 10(16): e35811, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39224309

RESUMO

Objectives: To comprehensively analyze the randomized controlled clinical trials of integrated traditional Chinese medicine (TCM) and western medicine in the treatment of metabolic syndrome (MetS), and to explore the clinical efficacy and safety of different TCM combined with western medicine for MetS. The purpose of this study is to provide specific suggestions for clinical guidance in the treatment of MetS. Methods: A comprehensive literature review was conducted across several databases, including China Knowledge Network, Wanfang Data, VIP Information, China Biomedical Literature Service System, Embase, PubMed, and Web of Science, up to October 2023. The scope of this review was confined to RCTs focusing on the treatment of metabolic syndrome through an integrated approach of TCM and Western medicine. The primary efficacy endpoints analyzed were clinical efficacy, fasting blood glucose (FBG), triglyceride (TG), and high-density lipoprotein (HDL). Data synthesis and analysis were performed using Stata 16 and RevMan 5.4 for both traditional and network meta-analyses. Results: The findings from both traditional and network meta-analyses reveal that the combination of JiangZhiHuoXue pills (JZHX) + Conventional Western Medicine (CWM) significantly reduces FBG levels. Similarly, the AnShenNingXin capsules (ASNX) + CWM combination markedly lowers TG levels, while the FuFangQiMa capsules (FFQM) + CWM combination shows enhanced efficacy in elevating HDL levels. Notably, the combination of KangNing capsules (KNJN) + CWM demonstrates a more pronounced clinical effect compared to CWM/placebo alone. Conclusions: The study concludes that the synergistic combination of TCM and Western medicine exhibits superior therapeutic benefits in treating MetS compared to CWM/Placebo treatments alone. The combinations of JZHX, AXNX, FFQM, and KNJN with CWM emerge as potentially effective treatments.

2.
Immunopharmacol Immunotoxicol ; : 1-11, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138614

RESUMO

Objective: The study aimed to explore the role of the Wnt/ß-catenin signaling pathway in pancreatic cancer progression and chemoresistance, with a focus on identifying specific factors that distinguish between normal and tumor cells, thereby offering potential therapeutic targets.Materials and Methods: We analyzed levels of total and phosphorylated eukaryotic translation initiation factor 4E (eIF4E) and ß-catenin in pancreatic cancer and normal pancreatic tissues. Functional assays were used to assess the impact of eIF4E phosphorylation on ß-catenin signaling, cell proliferation, and chemoresistance, with MNK kinase involvement determined through gene depletion studies. The MNK kinase inhibitor eFT508 was evaluated for its effects on eIF4E phosphorylation, ß-catenin activation, and cell viability in both in vitro and in vivo models of pancreatic cancer.Results: Both total and phosphorylated eIF4E, along with ß-catenin, were significantly elevated in pancreatic cancer tissues compared to normal tissues. Phosphorylation of eIF4E at serine 209 was shown to activate ß-catenin signaling, enhance cell proliferation, and contribute to chemoresistance in pancreatic cancer. Importantly, these effects were dependent on MNK kinase activity. Depletion of eIF4E reduced cell viability in both pancreatic cancer and normal cells, while depletion of MNK selectively decreased viability in pancreatic cancer cells. Treatment with eFT508 effectively inhibited eIF4E phosphorylation, suppressed ß-catenin activation, and reduced pancreatic cancer cell growth and survival in vitro and in vivo, with minimal impact on normal cells.Conclusions: The MNK-eIF4E-ß-catenin axis plays a critical role in pancreatic cancer progression and chemoresistance, distinguishing pancreatic cancer cells from normal cells. Targeting MNK kinases with inhibitors like eFT508 presents a promising therapeutic strategy for pancreatic cancer, with potential for selective efficacy and reduced toxicity.

3.
Cell Commun Signal ; 22(1): 401, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39148095

RESUMO

TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels.


Assuntos
Linfoma Difuso de Grandes Células B , Proteína Supressora de Tumor p53 , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Humanos , Proteína Supressora de Tumor p53/genética , Prognóstico , Mutação de Sentido Incorreto/genética , Mutação/genética , Microambiente Tumoral/genética , Masculino , Feminino , Fatores de Risco , Pessoa de Meia-Idade
4.
Diagn Pathol ; 19(1): 112, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39153970

RESUMO

The occurrence and progression of skin cutaneous melanoma (SKCM) is strongly associated with immune cells infiltrating the tumor microenvironment (TME). This study examined the expression, prognosis, and immune relevance of SIGLEC9 in SKCM using multiple online databases. Analysis of the GEPIA2 and Ualcan databases revealed that SIGLEC9 is highly expressed in SKCM, and patients with high SIGLEC9 expression had improved overall survival (OS). Furthermore, the mutation rate of SIGLEC9 in SKCM patients was found to be 5.41%, the highest observed. The expression of SIGLEC9 was positively correlated with macrophages, neutrophils and B cells, CD8 + T cells, CD4 + T cells, and dendritic cells, according to TIMER. Based on TCGA-SKCM data, we verified that high SIGLEC9 expression is closely associated with a good prognosis for SKCM patients, including overall survival, progression-free interval, and disease-specific survival. This positive prognosis could be due to the infiltration of immune cells into the TME. Additionally, our analysis of single-cell transcriptome data revealed that SIGLEC9 not only played a role in the normal skin immune microenvironment, but is also highly expressed in immune cell subpopulations of SKCM patients, regulating the immune response to tumors. Our findings suggest that the close association between SIGLEC9 and SKCM prognosis is primarily mediated by its effect on the tumor immune microenvironment.


Assuntos
Biomarcadores Tumorais , Melanoma , Neoplasias Cutâneas , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Melanoma/imunologia , Melanoma/genética , Melanoma/mortalidade , Melanoma/patologia , Prognóstico , Biomarcadores Tumorais/genética , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/genética , Melanoma Maligno Cutâneo , Antígenos CD/genética , Antígenos CD/metabolismo , Linfócitos do Interstício Tumoral/imunologia
5.
Nano Lett ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39196295

RESUMO

A major challenge for ultrasensitive analysis is the high-efficiency determination of different target single molecules in parallel with high accuracy. Herein, we developed a quantitative fluoro-electrochemical imaging approach for direct multiplexed single-molecule counting with a SiC-nanofilm-modified indium tin oxide transparent electrode. The nanofilm could control local pH through proton-coupled electron transfer in a lower potential range and further induce direct electrochemical oxidation of the dye molecules with a higher applied potential. The fluoro-electrochemical responses of immobilized single molecules with different pH values and redox behaviors could thus be distinguished within the same fluorescence channels. This method yields nonamplified direct counting of single molecules, as indicated by excellent linear responses in the picomolar range. The successful distinction of seven different randomly mixed dyes underscores the versatility and efficacy of the proposed method in the highly accurate determination of single dye molecules, paving the way for highly parallel single-molecule detection for diverse applications.

6.
Biomed Mater ; 19(5)2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39121891

RESUMO

Polymer nanomicelles have the advantages of small particle size, improved drug solubility, retention effect and enhanced permeability, so they can be used in the treatment of tumour diseases. The aim of this study was to prepare and optimise a nanomicelle which can improve the solubility of insoluble drugs. Firstly, the carboxyl group of cholesterol succinic acid monoester was grafted with the side chain amino group of O-carboxymethyl chitosan-g-cholesterol succinic acid monoester (CCMC), and its structure was characterized by fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H-NMR). Particle size has an important impact on tissue distribution, cell uptake, permeability and inhibition of tumour tissue. In this study, particle size and polydispersity index (PDI) were selected as indexes to optimise the preparation process of CCMC nanomicelles through single factor experiment, Plackett-Burman experiment, the steepest climbing experiment and response surface design experiment. The optimised CCMC nanomicelles showed an average particle size of 173.9 ± 2.3 nm and a PDI of 0.170 ± 0.053. The Cell Counting Kit-8 assay showed no significant effect on cell viability in the range of 0-1000 µg ml-1concentration. Coumarin-6 (C6) was used as a fluorescent probe to investigate the drug-carrying ability of CCMC nanomicelles. C6-CCMC showed 86.35 ± 0.56% encapsulation efficiency with a drug loading of 9.18 ± 0.32%. Both CCMC and C6-CCMC demonstrated excellent stability in different media. Moreover, under the same conditions, the absorption effect of C6 in C6-CCMC nanomicelles was significantly higher than that of free C6 while also exhibiting good sustained-release properties. Therefore, this study demonstrates CCMC nanomicelles as a promising new drug carrier that can significantly improve insoluble drug absorption.


Assuntos
Quitosana , Colesterol , Micelas , Tamanho da Partícula , Quitosana/química , Quitosana/análogos & derivados , Humanos , Colesterol/química , Colesterol/análogos & derivados , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas/química , Solubilidade , Polímeros/química , Portadores de Fármacos/química , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/química , Linhagem Celular Tumoral , Tiazóis/química , Tiazóis/farmacologia
7.
Adv Mater ; : e2407066, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39108048

RESUMO

The assembly and patterning engineering in two-dimensional (2D) materials hold importance for chip-level designs incorporating multifunctional detectors. At present, the patterning and stacking methods of 2D materials inevitably introduce impurity instability and functional limitations. Here, the space-confined chemical vapor deposition method is employed to achieve state-of-the-art kirigami structures of self-assembled WS2, featuring various layer combinations and stacking configurations. With this technique as a foundation, the WS2 nano-kirigami is integrated with metasurface design, achieving a photodetector with bidirectional polarization-sensitive detection capability in the infrared spectrum. Nano-kirigami can eliminate some of the uncontrollable factors in the processing of 2D material devices, providing a freely designed platform for chip-level multifunctional detection across multiple modules.

8.
Lipids Health Dis ; 23(1): 206, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951820

RESUMO

BACKGROUND: An imbalance in lipid metabolism has been linked to the development of AMD, but the causal relationship between AMD and plasma fatty acids (FAs) remains controversial. Using a two-sample Mendelian randomization (MR) approach, we sought to evaluate the impact of specific FA plasma levels on the risk of different AMD subtypes. METHODS: We analysed genome-wide association data of circulating FAs from 115,006 European-descended individuals in the UK Biobank. These data were used in a two-sample MR framework to assess the potential role of circulating FAs in developing wet and dry AMD. Sensitivity analyses were conducted to ensure the robustness of our findings. Additional multivariable and locus-specific MR analyses were conducted to evaluate direct effects of FA on AMD subtypes, minimizing biases from lipoprotein-related traits and triglycerides. RESULTS: Mendelian randomization revealed associations of omega-3 was associated with decreased wet (OR 0.78, 95%CI 0.66-0.92) and dry AMD (0.85, 0.74-0.97) risk, showed a protective effect on AMD. Notably, the omega-6 to omega-3 ratio showed potential causal effects on both wet (1.27, 1.03-1.56) and dry AMD (1.18, 1.02-1.37). Multivariable MR suggested that the causal relationship of omega-3, omega-6 to omega-3 ratio on wet AMD persists after conditioning on HDL, LDL and triglycerides, albeit with slightly diminished evidence strength. Locus-specific MR linked to omega-3(FADS1, 0.89, 0.82-0.98; FADS2, 0.88, 0.81-0.96) and omega-6 to omega-3 ratio (FADS1, 1.10, 1.02-1.20; FADS2, 1.11, 1.03-1.20) suggests causal effects of these factors on wet AMD. CONCLUSIONS: The associations between plasma FA concentrations and AMD, suggest potential causal role of omega-3, and the omega-6 to omega-3 ratio in wet AMD. These results underscore the impact of an imbalanced circulating omega-3 and omega-6 FA ratio on AMD pathophysiology from MR perspective.


Assuntos
Dessaturase de Ácido Graxo Delta-5 , Ácidos Graxos Ômega-3 , Ácidos Graxos Ômega-6 , Estudo de Associação Genômica Ampla , Degeneração Macular , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Humanos , Degeneração Macular/sangue , Degeneração Macular/genética , Ácidos Graxos Ômega-3/sangue , Masculino , Feminino , Ácidos Graxos Ômega-6/sangue , Idoso , Ácidos Graxos Dessaturases/genética , Pessoa de Meia-Idade , Triglicerídeos/sangue , Ácidos Graxos/sangue , Fatores de Risco
9.
Health Inf Sci Syst ; 12(1): 37, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38974364

RESUMO

Obtaining high-quality data sets from raw data is a key step before data exploration and analysis. Nowadays, in the medical domain, a large amount of data is in need of quality improvement before being used to analyze the health condition of patients. There have been many researches in data extraction, data cleaning and data imputation, respectively. However, there are seldom frameworks integrating with these three techniques, making the dataset suffer in accuracy, consistency and integrity. In this paper, a multi-source heterogeneous data enhancement framework based on a lakehouse MHDP is proposed, which includes three steps of data extraction, data cleaning and data imputation. In the data extraction step, a data fusion technique is offered to handle multi-modal and multi-source heterogeneous data. In the data cleaning step, we propose HoloCleanX, which provides a convenient interactive procedure. In the data imputation step, multiple imputation (MI) and the SOTA algorithm SAITS, are applied for different situations. We evaluate our framework via three tasks: clustering, classification and strategy prediction. The experimental results prove the effectiveness of our data enhancement framework.

10.
Virol Sin ; 39(4): 565-573, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38945213

RESUMO

Bats are the natural reservoir hosts for SARS-related coronavirus (SARSr-CoV) and other highly pathogenic microorganisms. Therefore, it is conceivable that an individual bat may harbor multiple microbes. However, there is limited knowledge on the overall co-circulation of microorganisms in bats. Here, we conducted a 16-year monitoring of bat viruses in south and central China and identified 238 SARSr-CoV positive samples across nine bat species from ten provinces or administrative districts. Among these, 76 individual samples were selected for further metagenomics analysis. We found a complex microenvironment characterized by the general co-circulation of microbes from two different sources: mammal-associated viruses or environment-associated microbes. The later includes commensal bacteria, enterobacteria-related phages, and insect or fungal viruses of food origin. Results showed that 25% (19/76) of the samples contained at least one another mammal-associated virus, notably alphacoronaviruses (13/76) such as AlphaCoV/YN2012, HKU2-related CoV and AlphaCoV/Rf-HuB2013, along with viruses from other families. Notably, we observed three viruses co-circulating within a single bat, comprising two coronavirus species and one picornavirus. Our analysis also revealed the potential presence of pathogenic bacteria or fungi in bats. Furthermore, we obtained 25 viral genomes from the 76 bat SARSr-CoV positive samples, some of which formed new evolutionary lineages. Collectively, our study reveals the complex microenvironment of bat microbiome, facilitating deeper investigations into their pathogenic potential and the likelihood of cross-species transmission.


Assuntos
Quirópteros , Coinfecção , Metagenômica , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Viroma , Quirópteros/virologia , Animais , China , Coinfecção/virologia , Coinfecção/veterinária , Coinfecção/microbiologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/genética , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/isolamento & purificação , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/classificação , Filogenia , Genoma Viral/genética , Reservatórios de Doenças/virologia
11.
Ann Hematol ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38886191

RESUMO

Diffuse large B-cell lymphoma (DLBCL), accounts for 30-40% of newly diagnosed lymphomas, has an overall cure rate of approximately 60%. Despite previous reports suggesting a negative prognostic association between CCND3 mutations and Burkitt lymphoma, their prognostic implications in DLBCL remain controversial. To investigate this, we evaluated CCND3 mutation status in 2059 DLBCL patient samples from four database (integrated cohort) and additional 167 DLBCL patient samples in our center (JSPH cohort). The mutation was identified in 5.5% (113/2059) of the cases in the integrated cohort, with 86% (97/113) found in exon 5. Furthermore, P284, R271, I290 and Q276 are described as CCND3 mutation hotspots. CCND3 mutation was associated with decreased overall survival (OS) in the integrated cohort (P = 0.0407). Further subgroup analysis revealed that patients diagnosed as EZB subtype DLBCL by LymphGen algorithm with CCND3 mutations had poorer OS than patients diagnosed as EZB subtype without CCND3 mutations (P = 0.0140). Using the next-generation sequencing (NGS) in the JSPH cohort, it was found that both cell cycle and DNA replication pathways were highly upregulated in patients with CCND3 mutations. Our results suggest that CCND3 mutations can serve as a novel prognostic factor in DLBCL pathogenesis. Consequently, the development of personalized therapeutic strategies for DLBCL patients with CCND3 mutations might enhance their prognosis.

12.
Talanta ; 278: 126432, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38917547

RESUMO

Given the threat to human health posed by the abuse of tetracycline (TC), the development of a portable, on-site methods for highly sensitive and rapid TC detection is crucial. In this work, we initially synthesized europium-doped silicon nanoparticles (SiEuNPs) through a facile one-pot microwave-assisted method. Due to its blue-red dual fluorescence emission (465 nm/621 nm), which was respectively attributed to the silicon nanoparticles and Eu3+, SiEuNPs were designed as a ratiometric fluorescent sensor for TC detection. For the dual-signal reverse response mechanism: TC quenched the blue emission from silicon nanoparticles through inner filter effect (IFE), and enhanced the red emission through "antenna effect" (AE) between TC and Eu3+, the nanoprobe was able to detect TC within a range of 0.2-10 µM with a limit of detection (LOD) of 10.7 nM. Notably, the equilibrium detection time was only 1 min, achieving rapid TC detection. Furthermore, TC was also measured in real samples (tap water, milk and honey) with recoveries ranging from 95.7 % to 117.0 %. More importantly, a portable smartphone-assisted on-site detection platform was developed, enabling real-time qualitative identification and semi-quantitative analysis of TC based on fluorescence color changes. This work not only provided a novel doped silicon nanoparticles strategy, but also constructed a ratiometric sensing platform with dual-signal reverse response for intuitive and real-time TC detection.


Assuntos
Európio , Corantes Fluorescentes , Nanopartículas , Silício , Smartphone , Tetraciclina , Európio/química , Silício/química , Nanopartículas/química , Tetraciclina/análise , Corantes Fluorescentes/química , Leite/química , Animais , Espectrometria de Fluorescência/métodos , Mel/análise , Limite de Detecção , Imagem Óptica , Poluentes Químicos da Água/análise
13.
Exp Eye Res ; 245: 109976, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38897270

RESUMO

This review examines the pivotal role of photoreceptor cells in ocular refraction development, focusing on dopamine (DA) as a key neurotransmitter. Contrary to the earlier view favoring cone cells, recent studies have highlighted the substantial contributions of both rod and cone cells to the visual signaling pathways that influence ocular refractive development. Notably, rod cells appeared to play a central role. Photoreceptor cells interact intricately with circadian rhythms, color vision pathways, and other neurotransmitters, all of which are crucial for the complex mechanisms driving the development of myopia. This review emphasizes that ocular refractive development results from a coordinated interplay between diverse cell types, signaling pathways, and neurotransmitters. This perspective has significant implications for unraveling the complex mechanisms underlying myopia and aiding in the development of more effective prevention and treatment strategies.


Assuntos
Miopia , Refração Ocular , Miopia/fisiopatologia , Miopia/metabolismo , Miopia/etiologia , Humanos , Refração Ocular/fisiologia , Animais , Dopamina/metabolismo , Células Fotorreceptoras Retinianas Cones/fisiologia , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Ritmo Circadiano/fisiologia , Transdução de Sinais/fisiologia , Células Fotorreceptoras de Vertebrados/fisiologia , Células Fotorreceptoras de Vertebrados/patologia
14.
Front Pharmacol ; 15: 1328142, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828454

RESUMO

Purpose: The aim of this study was to evaluate the bioequivalence of two formulations of rupatadine (10-mg tablets) under fasting and fed conditions in healthy Chinese subjects. Methods: A total of 72 subjects were randomly assigned to the fasting cohort (n = 36) and fed cohort (n = 36). Each cohort includes four single-dose observation periods and 7-day washout intervals. Blood samples were collected at several timepoints for up to 72 h post-dose. The plasma concentration of rupatadine and the major active metabolites (desloratadine and 3-hydroxydesloratadine) were analyzed by a validated HPLC-MS/MS method. The non-compartmental analysis method was employed to determine the pharmacokinetic parameters. Based on the within-subject standard deviation of the reference formulation, a reference-scaled average bioequivalence or average bioequivalence method was used to evaluate the bioequivalence of the two formulations. Results: For the fasting status, the reference-scaled average bioequivalence method was used to evaluate the bioequivalence of the maximum observed rupatadine concentration (Cmax; subject standard deviation > 0.294), while the average bioequivalence method was used to evaluate the bioequivalence of the area under the rupatadine concentration-time curve from time 0 to the last detectable concentration (AUC0-t) and from time 0 to infinity (AUC0-∞). The geometric mean ratio (GMR) of the test/reference for Cmax was 95.91%, and the upper bound of the 95% confidence interval was 95.91%. For AUC0-t and AUC0-∞ comparisons, the GMR and 90% confidence interval (CI) were 98.76% (93.88%-103.90%) and 98.71% (93.93%-103.75%), respectively. For the fed status, the subject standard deviation values of Cmax, AUC0-t, and AUC0-∞ were all <0.294; therefore, the average bioequivalence method was used. The GMR and 90% CI for Cmax, AUC0-t, and AUC0-∞ were 101.19% (91.64%-111.74%), 98.80% (94.47%-103.33%), and 98.63% (94.42%-103.03%), respectively. The two-sided 90% CI of the GMR for primary pharmacokinetic endpoints of desloratadine and 3-hydroxydesloratadine was also within 80%-125% for each cohort. These results met the bioequivalence criteria for highly variable drugs. All adverse events (AEs) were mild and transient. Conclusion: The test drug rupatadine fumarate showed a similar safety profile to the reference drug Wystamm® (J. Uriach y Compañía, S.A., Spain), and its pharmacokinetic bioequivalence was confirmed in healthy Chinese subjects based on fasting and postprandial status. Clinical trial registration: http://www.chinadrugtrials.org.cn/index.html, identifier CTR20213217.

15.
Leukemia ; 38(7): 1541-1552, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38750139

RESUMO

The clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma (ND-DLBCL) remains largely unexplored. One hundred ND-DLBCL patients were consecutively enrolled as training cohort and another 26 ND-DLBCL patients were prospectively enrolled in validation cohort. CSF-ctDNA positivity (CSF(+)) was identified in 25 patients (25.0%) in the training cohort and 7 patients (26.9%) in the validation cohort, extremely higher than CNS involvement rate detected by conventional methods. Patients with mutations of CARD11, JAK2, ID3, and PLCG2 were more predominant with CSF(+) while FAT4 mutations were negatively correlated with CSF(+). The downregulation of PI3K-AKT signaling, focal adhesion, actin cytoskeleton, and tight junction pathways were enriched in CSF(+) ND-DLBCL. Furthermore, pretreatment CSF(+) was significantly associated with poor outcomes. Three risk factors, including high CSF protein level, high plasma ctDNA burden, and involvement of high-risk sites were used to predict the risk of CSF(+) in ND-DLBCL. The sensitivity and specificity of pretreatment CSF-ctDNA to predict CNS relapse were 100% and 77.3%. Taken together, we firstly present the prevalence and the genomic and transcriptomic landscape for CSF-ctDNA(+) DLBCL and highlight the importance of CSF-ctDNA as a noninvasive biomarker in detecting and monitoring of CSF infiltration and predicting CNS relapse in DLBCL.


Assuntos
Biomarcadores Tumorais , DNA Tumoral Circulante , Linfoma Difuso de Grandes Células B , Mutação , Humanos , Linfoma Difuso de Grandes Células B/líquido cefalorraquidiano , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/líquido cefalorraquidiano , Biomarcadores Tumorais/genética , Idoso , Adulto , DNA Tumoral Circulante/líquido cefalorraquidiano , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Prognóstico , Idoso de 80 Anos ou mais , Adulto Jovem , Estudos Prospectivos
16.
Gastroenterology Res ; 17(2): 82-89, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38716287

RESUMO

Background: This study investigated the diagnostic efficacy of multi-slice spiral computed tomography (MSCT) perfusion imaging in evaluating peripancreatic infection in elderly patients with severe acute pancreatitis (SAP). Methods: A retrospective analysis was conducted on the clinical data of 110 elderly SAP patients treated at our hospital from March 2018 to August 2019. The study correlated MSCT perfusion imaging characteristics with peripancreatic infection in elderly SAP patients. Additionally, receiver operating characteristic (ROC) curves were constructed to assess the diagnostic performance of MSCT perfusion imaging parameters in evaluating peripancreatic infection in elderly SAP patients. Results: The results indicated that among all 110 elderly SAP patients, the incidence rate of peripancreatic infection was 20.91%, with a mortality rate of 0.91%. MSCT perfusion imaging revealed that after peripancreatic infection in elderly SAP patients, there was a decrease in pancreatic density, local enlargement of the pancreas, blurring of the pancreatic margins, and associated ascites. Compression/narrowing/occlusion of the splenic vein was observed in 22 patients, compression/narrowing/occlusion of the superior mesenteric vein in 17 patients, thickening/thrombosis of the portal vein in 19 patients, and collateral circulation in 21 patients. Compared to elderly SAP patients without peripancreatic infection, those with the infection showed prolonged peak times, reduced peak heights, and decreased blood flow. ROC analysis indicated that the combination of the three parameters (peak time, peak height, and blood flow) had higher specificity and area under the curve (AUC) than single parameters, with no significant difference in sensitivity between the combination and single parameters. Conclusions: In conclusion, combining the three key MSCT perfusion imaging parameters (peak time, peak height, and blood flow) can significantly enhance the predictive efficacy for the risk of peripancreatic infection in elderly SAP patients.

17.
Heliyon ; 10(7): e28520, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38689952

RESUMO

Purpose: The recognition of sepsis as a heterogeneous syndrome necessitates identifying distinct subphenotypes to select targeted treatment. Methods: Patients with sepsis from the MIMIC-IV database (2008-2019) were randomly divided into a development cohort (80%) and an internal validation cohort (20%). Patients with sepsis from the ICU database of Peking University People's Hospital (2008-2022) were included in the external validation cohort. Time-series k-means clustering analysis and dynamic time warping was performed to develop and validate sepsis subphenotypes by analyzing the trends of 21 vital signs and laboratory indicators within 24 h after sepsis onset. Inflammatory biomarkers were compared in the ICU database of Peking University People's Hospital, whereas treatment heterogeneity was compared in the MIMIC-IV database. Findings: Three sub-phenotypes were identified in the development cohort. Type A patients (N = 2525, 47%) exhibited stable vital signs and fair organ function, type B (N = 1552, 29%) was exhibited an obvious inflammatory response and stable organ function, and type C (N = 1251, 24%) exhibited severely impaired organ function with a deteriorating tendency. Type C demonstrated the highest mortality rate (33%) and levels of inflammatory biomarkers, followed by type B (24%), whereas type A exhibited the lowest mortality rate (11%) and levels of inflammatory biomarkers. These subphenotypes were confirmed in both the internal and external cohorts, demonstrating similar features and comparable mortality rates. In type C patients, survivors had significantly lower fluid intake within 24 h after sepsis onset (median 2891 mL, interquartile range (IQR) 1530-5470 mL) than that in non-survivors (median 4342 mL, IQR 2189-7305 mL). For types B and C, survivors showed a higher proportion of indwelling central venous catheters (p < 0.05). Conclusion: Three novel phenotypes of patients with sepsis were identified and validated using time-series data, revealing significant heterogeneity in inflammatory biomarkers, treatments, and consistency across cohorts.

18.
Opt Lett ; 49(9): 2273-2276, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691697

RESUMO

As a complex anisotropic medium, variation in birefringence within biological tissues is closely associated with numerous physiological behaviors and phenomena. In this Letter, we propose a polarization feature fusion method and corresponding polarimetric parameters, which exhibit excellent performance of capturing the birefringence dynamic variation process in complex anisotropic media. By employing the feature fusion method, we combine and transform polarization basis parameters (PBPs) to derive fused polarization feature parameters (FPPs) with explicit expressions. Subsequently, we conduct Monte Carlo (MC) simulation to demonstrate the effectiveness of the proposed FPPs from two variation dimensions of birefringence direction θ and modulus Δn. Leveraging mathematical modeling and linear transformations, we investigate and abstract their response patterns concerning θ and Δn. Finally, the experiments confirm that the FPPs show superior adaptability and interpretability in characterizing the birefringence dynamic process of turbid media. The findings presented in this study provide new, to the best of our knowledge, methodological insights of information extraction for computational polarimetry in biomedical research.

19.
Materials (Basel) ; 17(10)2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38793520

RESUMO

Magnesium matrix composites are essential lightweight metal matrix composites, following aluminum matrix composites, with outstanding application prospects in automotive, aerospace lightweight and biomedical materials because of their high specific strength, low density and specific stiffness, good casting performance and rich resources. However, the inherent low plasticity and poor fatigue resistance of magnesium hamper its further application to a certain extent. Many researchers have tried many strengthening methods to improve the properties of magnesium alloys, while the relationship between wear resistance and plasticity still needs to be further improved. The nanoparticles added exhibit a good strengthening effect, especially the ceramic nanoparticles. Nanoparticle-reinforced magnesium matrix composites not only exhibit a high impact toughness, but also maintain the high strength and wear resistance of ceramic materials, effectively balancing the restriction between the strength and toughness. Therefore, this work aims to provide a review of the state of the art of research on the matrix, reinforcement, design, properties and potential applications of nano-reinforced phase-reinforced magnesium matrix composites (especially ceramic nanoparticle-reinforced ones). The conventional and potential matrices for the fabrication of magnesium matrix composites are introduced. The classification and influence of ceramic reinforcements are assessed, and the factors influencing interface bonding strength between reinforcements and matrix, regulation and design, performance and application are analyzed. Finally, the scope of future research in this field is discussed.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38809722

RESUMO

Recent methods often introduce attention mechanisms into the skip connections of U-shaped networks to capture features. However, these methods usually overlook spatial information extraction in skip connections and exhibit inefficiency in capturing spatial and channel information. This issue prompts us to reevaluate the design of the skip-connection mechanism and propose a new deep-learning network called the Fusing Spatial and Channel Attention Network, abbreviated as FSCA-Net. FSCA-Net is a novel U-shaped network architecture that utilizes the Parallel Attention Transformer (PAT) to enhance the extraction of spatial and channel features in the skip-connection mechanism, further compensating for downsampling losses. We design the Cross-Attention Bridge Layer (CAB) to mitigate excessive feature and resolution loss when downsampling to the lowest level, ensuring meaningful information fusion during upsampling at the lowest level. Finally, we construct the Dual-Path Channel Attention (DPCA) module to guide channel and spatial information filtering for Transformer features, eliminating ambiguities with decoder features and better concatenating features with semantic inconsistencies between the Transformer and the U-Net decoder. FSCA-Net is designed explicitly for fine-grained segmentation tasks of multiple organs and regions. Our approach achieves over 48% reduction in FLOPs and over 32% reduction in parameters compared to the state-of-the-art method. Moreover, FSCA-Net outperforms existing segmentation methods on seven public datasets, demonstrating exceptional performance. The code has been made available on GitHub: https://github.com/Henry991115/FSCA-Net.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA