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1.
Int J Clin Pharm ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39276261

RESUMO

BACKGROUND: Tislelizumab combined with chemotherapy has shown significant clinical benefits in improving overall survival compared to chemotherapy alone for patients with extensive-stage small-cell lung cancer (ES-SCLC). AIM: This study aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy versus standard chemotherapy as a first-line treatment for ES-SCLC from the US payer perspective and the perspective of the Chinese healthcare system. METHOD: We conducted an economic evaluation using a Markov state-transition model, reflecting the US payer perspective and the perspective of the Chinese healthcare system. Baseline patient characteristics and essential clinical data were obtained from the RATIONALE-312 trial. The costs and utilities were derived from open-access databases and published literature. The primary outcomes measured included quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB). Uncertainties in the model were addressed by probabilistic sensitivity analysis (PSA) and one-way sensitivity analysis (OWSA). RESULTS: In the base-case analysis, the addition of tislelizumab to chemotherapy provided an incremental gain of 0.16 QALYs at an additional cost of $7430.73, resulting in an ICER of $46,132.33 per QALY. Although above the willingness-to-pay (WTP) threshold of China of $38,042.49 per QALY, the cost-effectiveness was marginal, with an INHB of - 0.03 QALYs and an INMB of $- 1303.06. In the US, despite a slightly higher effectiveness gain of 0.28 QALYs, the increased cost of $45,157.35 resulted in an unfavorable ICER of $163,885.06 per QALY, exceeding the US WTP threshold of $150,000.00. PSA showed probabilities of cost-effectiveness of tislelizumab plus chemotherapy at 17.18% in China and 40.41% in the US. CONCLUSION: Tislelizumab combined with chemotherapy was not a cost-effective first-line treatment option for ES-SCLC in China or the US; however, the margin of cost-effectiveness was narrow.

2.
Int J Biol Macromol ; 279(Pt 2): 135250, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39222778

RESUMO

Artemisia argyi Levl. et Vant. (A. argyi) is an important member of Asteraceae (Compositae) family, which has good medicinal potential and edible value. Phytochemical studies have shown that the A. argyi has a variety of bioactive components, mainly including polysaccharides, flavonoids, alkaloids, and volatile oil. More and more evidences show that A. argyi polysaccharide is a kind of representative pharmacological and biological active macromolecules, which has a variety of pharmacological activities in vitro and in vivo, such as estrogen-like effect, anti-bacterial, anti-tumor, anti-oxidant and immune regulation effect. As far as we know, there are few comprehensively reviews on A. argyi polysaccharide. This review aims to comprehensively and systematically review the research progress on the extractions and purifications, structural characteristics, pharmacological activities, structure-activity relationships, existing and potential applications of A. argyi polysaccharides in the past 12 years, in order to support their therapeutic potential and health functions. Finally, prospects were made for the further development and utilization of A. argyi polysaccharides in four fields: food, medicine, packaging materials, and daily chemicals.

3.
Diagnostics (Basel) ; 14(17)2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39272733

RESUMO

Automated tooth segmentation and identification on dental radiographs are crucial steps in establishing digital dental workflows. While deep learning networks have been developed for these tasks, their performance has been inferior in partially edentulous individuals. This study proposes a novel semi-supervised Transformer-based framework (SemiTNet), specifically designed to improve tooth segmentation and identification performance on panoramic radiographs, particularly in partially edentulous cases, and establish an open-source dataset to serve as a unified benchmark. A total of 16,317 panoramic radiographs (1589 labeled and 14,728 unlabeled images) were collected from various datasets to create a large-scale dataset (TSI15k). The labeled images were divided into training and test sets at a 7:1 ratio, while the unlabeled images were used for semi-supervised learning. The SemiTNet was developed using a semi-supervised learning method with a label-guided teacher-student knowledge distillation strategy, incorporating a Transformer-based architecture. The performance of SemiTNet was evaluated on the test set using the intersection over union (IoU), Dice coefficient, precision, recall, and F1 score, and compared with five state-of-the-art networks. Paired t-tests were performed to compare the evaluation metrics between SemiTNet and the other networks. SemiTNet outperformed other networks, achieving the highest accuracy for tooth segmentation and identification, while requiring minimal model size. SemiTNet's performance was near-perfect for fully dentate individuals (all metrics over 99.69%) and excellent for partially edentulous individuals (all metrics over 93%). In edentulous cases, SemiTNet obtained statistically significantly higher tooth identification performance than all other networks. The proposed SemiTNet outperformed previous high-complexity, state-of-the-art networks, particularly in partially edentulous cases. The established open-source TSI15k dataset could serve as a unified benchmark for future studies.

4.
Int J Biol Macromol ; 278(Pt 3): 134919, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39179070

RESUMO

Chrysanthemum morifolium Ramat. (C. morifolium), as a traditional ornamental plant, it has multiple values, including edible, economic, nutritional and even medicinal values, which is used as herbal medicine and a new food resource in the world. Polysaccharides are one of the main bioactive components in C. morifolium, which have various health benefits such as improving functional constipation, improving colitis, anti-glycosylation, antioxidant, anti-angiogenesis, immunomodulation, prebiotic, and α-glucosidase inhibitory activities. This paper describes the extraction, purification, structural characteristics, health benefits, structural-activity relationships, applications, and analyses the shortcomings of the major relevant studies exist on C. morifolium polysaccharides. In addition, the potential mechanisms of the health benefits of C. morifolium polysaccharides were summarized. This study can provide reference and direction for further research and development of C. morifolium polysaccharides.

5.
Eur Radiol ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39191996

RESUMO

OBJECTIVES: To investigate the potential of T1rho, a new quantitative imaging sequence for cancer, for pre and early intra-treatment prediction of treatment response in nasopharyngeal carcinoma (NPC) and compare the results with those of diffusion-weighted imaging (DWI). MATERIALS AND METHODS: T1rho and DWI imaging of primary NPCs were performed pre- and early intra-treatment in 41 prospectively recruited patients. The mean preT1rho, preADC, intraT1rho, intraADC, and % changes in T1rho (ΔT1rho%) and ADC (ΔADC%) were compared between residual and non-residual groups based on biopsy in all patients after chemoradiotherapy (CRT) with (n = 29) or without (n = 12) induction chemotherapy (IC), and between responders and non-responders to IC in the subgroup who received IC, using Mann-Whitney U-test. A p-value of < 0.05 indicated statistical significance. RESULTS: Significant early intra-treatment changes in mean T1rho (p = 0.049) and mean ADC (p < 0.01) were detected (using paired t-test), most showing a decrease in T1rho (63.4%) and an increase in ADC (95.1%). Responders to IC (n = 17), compared to non-responders (n = 12), showed higher preT1rho (64.0 ms vs 66.5 ms) and a greater decrease in ΔT1rho% (- 7.5% vs 1.3%) (p < 0.05). The non-residual group after CRT (n = 35), compared to the residual group (n = 6), showed higher intraADC (0.96 vs 1.09 × 10-3 mm2/s) and greater increase in ΔADC% (11.7% vs 27.0%) (p = 0.02). CONCLUSION: Early intra-treatment changes are detectable on T1rho and show potential to predict tumour shrinkage after IC. T1rho may be complementary to DWI, which, unlike T1rho, did not predict response to IC but did predict non-residual disease after CRT. CLINICAL RELEVANCE STATEMENT: T1rho has the potential to complement DWI in the prediction of treatment response. Unlike DWI, it predicted shrinkage of the primary NPC after IC but not residual disease after CRT. KEY POINTS: Changes in T1rho were detected early during cancer treatment for NPC. Pre-treatment and early intra-treatment change in T1rho predicted response to IC, but not residual disease after CRT. T1rho can be used to complement DWI with DWI predicting residual disease after CRT.

6.
Curr Issues Mol Biol ; 46(8): 7862-7876, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39194683

RESUMO

Water pollution remains a major environmental concern, with increased toxic by-products being released into water bodies. Many of these chemical contaminants persist in the environment and bio-accumulate in aquatic organisms. At present, toxicological tests are mostly based on laboratory tests, and effective methods for monitoring wild aquatic environments remain lacking. In the present study, we used a well-characterized toxic chemical, 3,3',4,4',5-polychlorinated biphenyl (PCB126), as an example to try to identify common biomarker genes to be used for predictive toxicity of this toxic substance. First, we used two laboratory fish models, the zebrafish (Danio rerio) and medaka (Oryzias latipes), to expose PCB126 to obtain liver transcriptomic data by RNA-seq. Comparative transcriptomic analyses indicated generally conserved and concerted changes from the two species, thus validating the transcriptomic data for biomarker gene selection. Based on the common up- and downregulated genes in the two species, we selected nine biomarker genes to further test in other fish species. The first validation experiment was carried out using the third fish species, Mozambique tilapia (Oreochromis mossambicus), and essentially, all these biomarker genes were validated for consistent responses with the two laboratory fish models. Finally, to develop universal PCR primers suitable for potentially all teleost fish species, we designed degenerate primers and tested them in the three fish species as well as in another fish species without a genomic sequence available: guppy (Poecilia reticulata). We found all the biomarker genes showed consistent response to PCB126 exposure in at least 50% of the species. Thus, our study provides a promising strategy to identify common biomarker genes to be used for teleost fish analyses. By using degenerate PCR primers and analyzing multiple biomarker genes, it is possible to develop diagnostic PCR arrays to predict water contamination from any wild fish species sampled in different water bodies.

7.
Anal Chem ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023238

RESUMO

The adjustment of the emission wavelengths and cell permeability of the perylene diimides (PDI) for multicolor cell imaging is a great challenge. Herein, based on a bay-region substituent engineering strategy, multicolor perylene diimides (MCPDI) were rationally designed and synthesized by introducing azetidine substituents on the bay region of PDIs. With the fine-tuned electron-donating ability of the azetidine substituents, these MCPDI showed high brightness, orange, red, and near infrared (NIR) fluorescence along with Stokes shifts increasing from 35 to 110 nm. Interestingly, azetidine substituents distorted to the plane of the MCPDI dyes, and the twist angle of monosubstituted MCPDI was larger than that of disubstituted MCPDI, which might efficiently decrease their π-π stacking. Moreover, all of these MCPDI dyes were cell-permeable and selectively stained various organelles for multicolor imaging of multiple organelles in living cells. Two-color imaging of lipid droplets (LDs) and other organelles stained with MCPDI dyes was performed to reveal the interaction between the LDs and other organelles in living cells. Furthermore, a NIR-emitting MCPDI dye with a mitochondria-targeted characteristic was successfully applied for tumor-specific imaging. The facile synthesis, excellent stability, high brightness, tunable fluorescence emission, and Stokes shifts make these MCPDI promising fluorescent probes for biological applications.

8.
Int J Antimicrob Agents ; 64(2): 107258, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38914142

RESUMO

Tandem amplification of carbapenemase genes increases gene copy number and enhances carbapenem resistance. These amplifications are often heterogeneous, transient, and located on plasmids, which also contribute to heteroresistance. Amplification of encoding genes is especially important for enzymes with low hydrolysis activity, which are often overlooked. Here, we reported an intrinsic oxacillinase oxaAb amplification flanked by ISAba1. The amplification is in the chromosome and contains up to 25 repeats. We provided genomic, transcriptomic, and proteomic evidence that the amplification resulted in oxacillinase overproduction. Notably, no point mutations of oxaAb were found during the amplification process. Strains of Acinetobacter baumannii with intrinsic amplified or external transformed ISAba1-oxaAb exhibited higher meropenem hydrolysis activity. Furthermore, the number of repeats in the amplification decreased gradually over a period of 21 d cultured with carbapenem withdrawal. However, upon re-exposure to meropenem, the ISAba1 flanked oxaAb responded rapidly, with repeat numbers reaching or exceeding pre-carbapenem withdrawal levels within 24 h. Taken together, these findings suggest that ISAba1-mediated gene amplification and overproduction of intrinsic low-activity oxacillinase oxaAb resulted in carbapenem resistance.


Assuntos
Acinetobacter baumannii , Antibacterianos , Carbapenêmicos , beta-Lactamases , Acinetobacter baumannii/genética , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/enzimologia , beta-Lactamases/genética , Carbapenêmicos/farmacologia , Antibacterianos/farmacologia , Amplificação de Genes , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Cromossomos Bacterianos/genética , Humanos , Meropeném/farmacologia , Elementos de DNA Transponíveis/genética
9.
Pflugers Arch ; 476(8): 1249-1261, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38940824

RESUMO

Chronic cerebral ischemia (CCI) is a common neurological disorder, characterized by progressive cognitive impairment. Acupoint catgut embedding (ACE) represents a modern acupuncture form that has shown neuroprotective effects; nevertheless, its effects on CCI and the mechanisms remain largely unknown. Here, we aimed to explore the therapeutic action of ACE in CCI-induced cognitive impairment and its mechanisms. The cognitive function of CCI rats was determined using Morris water maze test, and histopathological changes in the brain were assessed through hematoxylin-eosin (HE) staining. To further explore the molecular mechanisms, the expression levels of oxidative stress markers and the Ang II/AT1R/NOX axis-associated molecules in the hippocampus were evaluated using enzyme-linked immunosorbent assay (ELISA), western blotting, and immunohistochemistry. Here, we observed that ACE treatment alleviated cognitive dysfunction and histopathological injury in CCI rats. Intriguingly, candesartan (an AT1R blocker) enhanced the beneficial effects of ACE on ameliorating cognitive impairment in CCI rats. Mechanistically, ACE treatment blocked the Ang II/AT1R/NOX pathway and subsequently suppressed oxidative stress, thus mitigating cognitive impairment in CCI. Our findings first reveal that ACE treatment could suppress cognitive impairment in CCI, which might be partly due to the suppression of Ang II/AT1R/NOX axis.


Assuntos
Pontos de Acupuntura , Angiotensina II , Isquemia Encefálica , Disfunção Cognitiva , Estresse Oxidativo , Receptor Tipo 1 de Angiotensina , Animais , Masculino , Ratos , Terapia por Acupuntura/métodos , Angiotensina II/metabolismo , Isquemia Encefálica/metabolismo , Categute , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/etiologia , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/metabolismo
11.
Oral Oncol ; 152: 106796, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38615586

RESUMO

OBJECTIVES: Parotid gland tumors (PGTs) often occur as incidental findings on magnetic resonance images (MRI) that may be overlooked. This study aimed to construct and validate a deep learning model to automatically identify parotid glands (PGs) with a PGT from normal PGs, and in those with a PGT to segment the tumor. MATERIALS AND METHODS: The nnUNet combined with a PG-specific post-processing procedure was used to develop the deep learning model trained on T1-weighed images (T1WI) in 311 patients (180 PGs with tumors and 442 normal PGs) and fat-suppressed (FS)-T2WI in 257 patients (125 PGs with tumors and 389 normal PGs), for detecting and segmenting PGTs with five-fold cross-validation. Additional validation set separated by time, comprising T1WI in 34 and FS-T2WI in 41 patients, was used to validate the model performance. RESULTS AND CONCLUSION: To identify PGs with tumors from normal PGs, using combined T1WI and FS-T2WI, the deep learning model achieved an accuracy, sensitivity and specificity of 98.2% (497/506), 100% (119/119) and 97.7% (378/387), respectively, in the cross-validation set and 98.5% (67/68), 100% (20/20) and 97.9% (47/48), respectively, in the validation set. For patients with PGTs, automatic segmentation of PGTs on T1WI and FS-T2WI achieved mean dice coefficients of 86.1% and 84.2%, respectively, in the cross-validation set, and of 85.9% and 81.0%, respectively, in the validation set. The proposed deep learning model may assist the detection and segmentation of PGTs and, by acting as a second pair of eyes, ensure that incidentally detected PGTs on MRI are not missed.


Assuntos
Aprendizado Profundo , Imageamento por Ressonância Magnética , Neoplasias Parotídeas , Humanos , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/patologia , Imageamento por Ressonância Magnética/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/patologia , Adulto Jovem , Adolescente , Processamento de Imagem Assistida por Computador/métodos , Idoso de 80 Anos ou mais
13.
Int J Biol Macromol ; 267(Pt 1): 131499, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38614164

RESUMO

The genus Lilium (Lilium) has been widely used in East Asia for over 2000 years due to its rich nutritional and medicinal value, serving as both food and medicinal ingredient. Polysaccharides, as one of the most important bioactive components in Lilium, offer various health benefits. Recently, polysaccharides from Lilium plants have garnered significant attention from researchers due to their diverse biological properties including immunomodulatory, anti-oxidant, anti-diabetic, anti-tumor, anti-bacterial, anti-aging and anti-radiation effects. However, the limited comprehensive understanding of polysaccharides from Lilium plants has hindered their development and utilization. This review focuses on the extraction, purification, structural characteristics, biological activities, structure-activity relationships, applications, and relevant bibliometrics of polysaccharides from Lilium plants. Additionally, it delves into the potential development and future research directions. The aim of this article is to provide a comprehensive understanding of polysaccharides from Lilium plants and to serve as a basis for further research and development as therapeutic agents and multifunctional biomaterials.


Assuntos
Lilium , Polissacarídeos , Lilium/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/isolamento & purificação , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Relação Estrutura-Atividade , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação
15.
Diabetes Metab ; 50(3): 101526, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38458351

RESUMO

AIM: This study aimed to investigate the association of social isolation, loneliness, and their trajectory with the risk of developing type 2 diabetes mellitus (T2DM) across genetic risk. METHODS: We included 439,337 participants (mean age 56.3 ± 8.1 years) enrolled in the UK Biobank study who were followed up until May 31, 2021. Social isolation and loneliness were self-reported and were further categorized into never, transient, incident, and persistent patterns. RESULTS: During a median follow-up of 12.7 years, 15,258 incident T2DM cases were documented. Social isolation (versus no social isolation: hazard ratio (HR) 95 % confidence interval (CI) 1.04 [1.00;1.09]) and loneliness (versus no loneliness: 1.26 [1.19;1.34]) were associated with an increased T2DM risk, independent of the genetic risk for T2DM. The interactions existed between social isolation and loneliness (Pinteraction < 0.05); the increased T2DM risk associated with social isolation was only significant among participants without loneliness. In the longitudinal analysis, only persistent social isolation (versus never social isolation: 1.22 [1.02;1.45]) was associated with an increased T2DM risk, whereas incident loneliness (versus never loneliness: 1.95 [1.40;2.71]) and persistent loneliness (2.00 [1.31;3.04]) were associated with higher T2DM risks. CONCLUSION: Social isolation and loneliness, especially their persistent pattern, were independently associated with an increased incident T2DM risk, irrespective of an individual's genetic risk. Loneliness modified the association between social isolation and incident T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Solidão , Isolamento Social , Humanos , Diabetes Mellitus Tipo 2/psicologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Solidão/psicologia , Isolamento Social/psicologia , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Incidência , Fatores de Risco , Predisposição Genética para Doença , Reino Unido/epidemiologia , Adulto , Estratificação de Risco Genético
16.
Abdom Radiol (NY) ; 49(6): 1805-1815, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38462557

RESUMO

OBJECTIVE: We aim to construct a magnetic resonance imaging (MRI)-based multi-sequence multi-regional radiomics model that will improve the preoperative prediction ability of lymph node metastasis (LNM) in T3 rectal cancer. METHODS: Multi-sequence MRI data from 190 patients with T3 rectal cancer were retrospectively analyzed, with 94 patients in the LNM group and 96 patients in the non-LNM group. The clinical factors, subjective imaging features, and the radiomic features of tumor and peritumoral mesorectum region of patients were extracted from T2WI and ADC images. Spearman's rank correlation coefficient, Mann-Whitney's U test, and the least absolute shrinkage and selection operator were used for feature selection and dimensionality reduction. Logistic regression was used to construct six models. The predictive performance of each model was evaluated by the receiver operating characteristic curve (ROC). The differences of each model were characterized by area under the curve (AUC) via the DeLong test. RESULTS: The AUCs of T2WI, ADC single-sequence radiomics model and multi-sequence radiomics model were 0.73, 0.75, and 0.78, respectively. The multi-sequence multi-regional radiomics model with improved performance was created by combining the radiomics characteristics of the peritumoral mesorectum region with the multi-sequence radiomics model (AUC, 0.87; p < 0.01). The AUC of the clinical model was 0.68, and the MRI-clinical composite evaluation model was obtained by incorporating the clinical data with the multi-sequence multi-regional radiomics features, with an AUC of 0.89. CONCLUSION: The MRI-based multi-sequence multi-regional radiomics model significantly improved the prediction ability of LNM for T3 rectal cancer and could be applied to guide surgical decision-making in patients with T3 rectal cancer.


Assuntos
Metástase Linfática , Imageamento por Ressonância Magnética , Neoplasias Retais , Humanos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Metástase Linfática/diagnóstico por imagem , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Idoso , Valor Preditivo dos Testes , Adulto , Estadiamento de Neoplasias , Radiômica
17.
Diagnostics (Basel) ; 14(5)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38473016

RESUMO

Skeletal Class III malocclusion is one type of dentofacial deformity that significantly affects patients' facial aesthetics and oral health. The orthodontic treatment of skeletal Class III malocclusion presents challenges due to uncertainties surrounding mandibular growth patterns and treatment outcomes. In recent years, disease-specific radiographic features have garnered interest from researchers in various fields including orthodontics, for their exceptional performance in enhancing diagnostic precision and treatment effect predictability. The aim of this narrative review is to provide an overview of the valuable radiographic features in the diagnosis and management of skeletal Class III malocclusion. Based on the existing literature, a series of analyses on lateral cephalograms have been concluded to identify the significant variables related to facial type classification, growth prediction, and decision-making for tooth extractions and orthognathic surgery in patients with skeletal Class III malocclusion. Furthermore, we summarize the parameters regarding the inter-maxillary relationship, as well as different anatomical structures including the maxilla, mandible, craniofacial base, and soft tissues from conventional and machine learning statistical models. Several distinct radiographic features for Class III malocclusion have also been preliminarily observed using cone beam computed tomography (CBCT) and magnetic resonance imaging (MRI).

18.
Eur J Pharmacol ; 968: 176404, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38382804

RESUMO

ß-thalassemia, a globally prevalent genetic disorder, urgently requires innovative treatment options. Fetal hemoglobin (HbF) induction stands as a key therapeutic approach. This investigation focused on Ginsenoside Rg1 from the Panax genus for HbF induction. Employing K562 cells and human erythroid precursor cells (ErPCs) derived from neonatal cord blood, the study tested Rg1 at different concentrations. We measured its effects on γ-globin mRNA levels and HbF expression, alongside assessments of cell proliferation and differentiation. In K562 cells, Rg1 at 400 µM significantly increased γ-globin mRNA expression by 4.24 ± 1.08-fold compared to the control. In ErPCs, the 800 µM concentration was most effective, leading to an over 80% increase in F-cells and a marked upregulation in HbF expression. Notably, Rg1 did not adversely affect cell proliferation or differentiation, with the 200 µM concentration showing an increase in γ-globin mRNA by 2.33 ± 0.58-fold, and the 800 µM concentration enhancing HbF expression by 2.59 ± 0.03-fold in K562 cells. Our results underscore Rg1's potential as an effective and safer alternative for ß-thalassemia treatment. By significantly enhancing HbF levels without cytotoxicity, Rg1 offers a notable advantage over traditional treatments like Hydroxyurea. While promising, these in vitro findings warrant further in vivo exploration to confirm Rg1's therapeutic efficacy and to unravel its underlying mechanistic pathways.


Assuntos
Ginsenosídeos , Talassemia beta , Recém-Nascido , Humanos , Talassemia beta/genética , Hemoglobina Fetal , gama-Globinas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
19.
J Natl Cancer Inst ; 116(5): 665-672, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38171488

RESUMO

BACKGROUND: Although contrast-enhanced magnetic resonance imaging (MRI) detects early-stage nasopharyngeal carcinoma (NPC) not detected by endoscopic-guided biopsy (EGB), a short contrast-free screening MRI would be desirable for NPC screening programs. This study evaluated a screening MRI in a plasma Epstein-Barr virus (EBV)-DNA NPC screening program. METHODS: EBV-DNA-screen-positive patients underwent endoscopy, and endoscopy-positive patients underwent EGB. EGB was negative if the biopsy was negative or was not performed. Patients also underwent a screening MRI. Diagnostic performance was based on histologic confirmation of NPC in the initial study or during a follow-up period of at least 2 years. RESULTS: The study prospectively recruited 354 patients for MRI and endoscopy; 40/354 (11.3%) endoscopy-positive patients underwent EGB. Eighteen had NPC (5.1%), and 336 without NPC (94.9%) were followed up for a median of 44.8 months. MRI detected additional NPCs in 3/18 (16.7%) endoscopy-negative and 2/18 (11.1%) EGB-negative patients (stage I/II, n = 4; stage III, n = 1). None of the 24 EGB-negative patients who were MRI-negative had NPC. MRI missed NPC in 2/18 (11.1%), one of which was also endoscopy-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI, endoscopy, and EGB were 88.9%, 91.1%, 34.8%, 99.4%, and 91.0%; 77.8%, 92.3%, 35.0%, 98.7%, and 91.5%; and 66.7%, 92.3%, 31.6%, 98.1%, and 91.0%, respectively. CONCLUSION: A quick contrast-free screening MRI complements endoscopy in NPC screening programs. In EBV-screen-positive patients, MRI enables early detection of NPC that is endoscopically occult or negative on EGB and increases confidence that NPC has not been missed.


Assuntos
Detecção Precoce de Câncer , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Imageamento por Ressonância Magnética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/virologia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Imageamento por Ressonância Magnética/métodos , Detecção Precoce de Câncer/métodos , Adulto , Herpesvirus Humano 4/isolamento & purificação , Carcinoma Nasofaríngeo/virologia , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/patologia , Estudos Prospectivos , Idoso , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , DNA Viral/sangue , Carcinoma/diagnóstico por imagem , Carcinoma/virologia , Carcinoma/diagnóstico , Carcinoma/patologia , Sensibilidade e Especificidade , Endoscopia/métodos , Estadiamento de Neoplasias , Programas de Rastreamento/métodos , Meios de Contraste/administração & dosagem
20.
Int J Clin Pharm ; 46(1): 158-165, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37991664

RESUMO

BACKGROUND: Although nivolumab has shown clinical benefits for relapsed malignant mesothelioma, its cost-effectiveness requires further investigation. AIM: This study aimed to evaluate the cost-effectiveness of nivolumab compared to placebo for relapsed malignant mesotheliomas from the perspective of the Chinese healthcare system. METHOD: A three-state Markov model was developed based on data from the phase 3 randomized CONFIRM clinical trial. The drug cost and utility values for the health state were obtained from the relevant literature. The measured outcomes included quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). Probabilistic and one-way sensitivity analyses (OWSA) were performed to assess the uncertainty of the model. RESULTS: Patients receiving nivolumab gained more health benefits (0.65 QALYs vs. 0.43 QALYs). The cost was higher ($25,806.08 vs. $9,310.74) than for patients in the placebo group, resulting in an ICER of $75,805.11/QALY, which was above the willingness-to-pay (WTP) threshold of three times per capita GDP ($35,864.61) in China. The result of OWSA indicated that the cost of nivolumab, the utility of the disease progression, and the discount rate were the most significant factors. Probabilistic sensitivity analysis suggested that the probability that nivolumab was not cost-effective as was 100.00% above the specified WTP threshold. CONCLUSION: From the perspective of the Chinese healthcare system, nivolumab was not as cost-effective as placebo for relapsed malignant mesothelioma.


Assuntos
Mesotelioma Maligno , Nivolumabe , Humanos , Nivolumabe/uso terapêutico , Mesotelioma Maligno/tratamento farmacológico , Análise de Custo-Efetividade , Análise Custo-Benefício , Recidiva Local de Neoplasia/tratamento farmacológico
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