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1.
Cancer Med ; 13(7): e7092, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38581123

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) accounts for the majority of gastric cancer (GC) cases globally. The present study found that H. pylori promoted GC stem cell (CSC)-like properties, therefore, the regulatory mechanism of how H. pylori promotes GC stemness was explored. METHODS: Spheroid-formation experiments were performed to explore the self-renewal capacity of GC cells. The expression of R-spondin 3 (RSPO3), Nanog homeobox, organic cation/carnitine transporter-4 (OCT-4), SRY-box transcription factor 2 (SOX-2), CD44, Akt, glycogen synthase kinase-3ß (GSK-3ß), p-Akt, p-GSK-3ß, ß-catenin, and G protein subunit gamma 7 (GNG7) were detected by RT-qPCR, western blotting, immunohistochemistry (IHC), and immunofluorescence. Co-immunoprecipitation (CoIP) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) were performed to identify proteins interacting with RSPO3. Lentivirus-based RNA interference constructed short hairpin (sh)-RSPO3 GC cells. Small interfering RNA transfection was performed to inhibit GNG7. The in vivo mechanism was verified using a tumor peritoneal seeding model in nude mice. RESULTS: H. pylori extracts promoted a CSC-like phenotype in GC cells and elevated the expression of RSPO3. RSPO3 knockdown significantly reduced the CSC-like properties induced by H. pylori. Previous studies have demonstrated that RSPO3 potentiates the Wnt/ß-catenin signaling pathway, but the inhibitor of Wnt cannot diminish the RSPO3-induced activation of ß-catenin. CoIP and LC-MS/MS revealed that GNG7 is one of the transmembrane proteins interacting with RSPO3, and it was confirmed that RSPO3 directly interacted with GNG7. Recombinant RSPO3 protein increased the phosphorylation level of Akt and GSK-3ß, and the expression of ß-catenin in GC cells, but this regulatory effect of RSPO3 could be blocked by GNG7 knockdown. Of note, GNG7 suppression could diminish the promoting effect of RSPO3 to CSC-like properties. In addition, RSPO3 suppression inhibited MKN45 tumor peritoneal seeding in vivo. IHC staining also showed that RSPO3, CD44, OCT-4, and SOX-2 were elevated in H. pylori GC tissues. CONCLUSION: RSPO3 enhanced the stemness of H. pylori extracts-infected GC cells through the GNG7/ß-catenin signaling pathway.


Assuntos
Helicobacter pylori , Neoplasias Gástricas , Animais , Camundongos , Helicobacter pylori/fisiologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Camundongos Nus , Cromatografia Líquida , Linhagem Celular Tumoral , Espectrometria de Massas em Tandem , Via de Sinalização Wnt , Neoplasias Gástricas/patologia , Células-Tronco Neoplásicas/metabolismo , Proliferação de Células
2.
Nat Commun ; 15(1): 3247, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622169

RESUMO

Photo-crosslinking polymerization stands as a fundamental pillar in the domains of chemistry, biology, and medicine. Yet, prevailing strategies heavily rely on ultraviolet/visible (UV/Vis) light to elicit in situ crosslinking. The inherent perils associated with UV radiation, namely the potential for DNA damage, coupled with the limited depth of tissue penetration exhibited by UV/Vis light, severely restrict the scope of photo-crosslinking within living organisms. Although near-infrared light has been explored as an external excitation source, enabling partial mitigation of these constraints, its penetration depth remains insufficient, particularly within bone tissues. In this study, we introduce an approach employing X-ray activation for deep-tissue hydrogel formation, surpassing all previous boundaries. Our approach harnesses a low-dose X-ray-activated persistent luminescent phosphor, triggering on demand in situ photo-crosslinking reactions and enabling the formation of hydrogels in male rats. A breakthrough of our method lies in its capability to penetrate deep even within thick bovine bone, demonstrating unmatched potential for bone penetration. By extending the reach of hydrogel formation within such formidable depths, our study represents an advancement in the field. This application of X-ray-activated polymerization enables precise and safe deep-tissue photo-crosslinking hydrogel formation, with profound implications for a multitude of disciplines.


Assuntos
Hidrogéis , Raios Ultravioleta , Masculino , Animais , Bovinos , Ratos , Hidrogéis/química , Raios X , Polimerização , Raios Infravermelhos
3.
Comput Biol Med ; 174: 108489, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38640633

RESUMO

Deep neural networks (DNNs) involve advanced image processing but depend on large quantities of high-quality labeled data. The presence of noisy data significantly degrades the DNN model performance. In the medical field, where model accuracy is crucial and labels for pathological images are scarce and expensive to obtain, the need to handle noisy data is even more urgent. Deep networks exhibit a memorization effect, they tend to prioritize remembering clean labels initially. Therefore, early stopping is highly effective in managing learning with noisy labels. Previous research has often concentrated on developing robust loss functions or implementing training constraints to mitigate the impact of noisy labels; however, such approaches have frequently resulted in underfitting. We propose using knowledge distillation to slow the learning process of the target network rather than preventing late-stage training from being affected by noisy labels. In this paper, we introduce a data sample self-selection strategy based on early stopping to filter out most of the noisy data. Additionally, we employ the distillation training method with dual teacher networks to ensure the steady learning of the student network. The experimental results show that our method outperforms current state-of-the-art methods for handling noisy labels on both synthetic and real-world noisy datasets. In particular, on the real-world pathological image dataset Chaoyang, the highest classification accuracy increased by 2.39 %. Our method leverages the model's predictions based on training history to select cleaner datasets and retrains them using these cleaner datasets, significantly mitigating the impact of noisy labels on model performance.

4.
Nat Rev Chem ; 8(4): 238-255, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38514833

RESUMO

Photon upconversion is a method for harnessing high-energy excited states from low-energy photons. Such photons, particularly in the red and near-infrared wavelength ranges, can penetrate tissue deeply and undergo less competitive absorption in coloured reaction media, enhancing the efficiency of large-scale reactions and in vivo phototherapy. Among various upconversion methodologies, the organic-based triplet-triplet annihilation upconversion (TTA-UC) stands out - demonstrating high upconversion efficiencies, requiring low excitation power densities and featuring tunable absorption and emission wavelengths. These factors contribute to improved photochemical reactions for fields such as photoredox catalysis, photoactivation, 3D printing and immunotherapy. In this Review, we explore concepts and design principles of organic TTA-UC-mediated photochemical reactions, highlighting notable advancements in the field, as well as identify challenges and propose potential solutions. This Review sheds light on the potential of organic TTA-UC to advance beyond the traditional photochemical reactions and paves the way for research in various fields and clinical applications.

5.
J Alzheimers Dis ; 98(3): 941-955, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38489185

RESUMO

Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina. Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study. Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk. Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants. Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Disfunção Cognitiva , Demência , Masculino , Feminino , Humanos , Idoso , Estudos de Coortes , Estudos de Casos e Controles , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Disfunção Cognitiva/epidemiologia , China/epidemiologia , Material Particulado/efeitos adversos , Material Particulado/análise
6.
EMBO Mol Med ; 16(4): 1027-1045, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38448545

RESUMO

Clinical deployment of oligonucleotides requires delivery technologies that improve stability, target tissue accumulation and cellular internalization. Exosomes show potential as ideal delivery vehicles. However, an affordable generalizable system for efficient loading of oligonucleotides on exosomes remain lacking. Here, we identified an Exosomal Anchor DNA Aptamer (EAA) via SELEX against exosomes immobilized with our proprietary CP05 peptides. EAA shows high binding affinity to different exosomes and enables efficient loading of nucleic acid drugs on exosomes. Serum stability of thrombin inhibitor NU172 was prolonged by exosome-loading, resulting in increased blood flow after injury in vivo. Importantly, Duchenne Muscular Dystrophy PMO can be readily loaded on exosomes via EAA (EXOEAA-PMO). EXOEAA-PMO elicited significantly greater muscle cell uptake, tissue accumulation and dystrophin expression than PMO in vitro and in vivo. Systemic administration of EXOEAA-PMO elicited therapeutic levels of dystrophin restoration and functional improvements in mdx mice. Altogether, our study demonstrates that EAA enables efficient loading of different nucleic acid drugs on exosomes, thus providing an easy and generalizable strategy for loading nucleic acid therapeutics on exosomes.


Assuntos
Exossomos , Distrofia Muscular de Duchenne , Animais , Camundongos , Distrofina/genética , Camundongos Endogâmicos mdx , Exossomos/metabolismo , Morfolinos/metabolismo , Morfolinos/farmacologia , Morfolinos/uso terapêutico , Distrofia Muscular de Duchenne/tratamento farmacológico , Distrofia Muscular de Duchenne/genética , Oligonucleotídeos/metabolismo , Oligonucleotídeos/uso terapêutico
8.
Chin J Traumatol ; 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38262890

RESUMO

PURPOSE: To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis. METHODS: A total of 282 healthy young male volunteers aged 18 - 20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conforms to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q1, Q3) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy. RESULTS: Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4 % (66 cases). These patients showed higher percentages of lean body mass (p = 0.001), total body water (TBW, p = 0.006), extracellular water (p = 0.020) and intracellular water (p = 0.010) as well as a larger ratio of basal metabolic rate/total weight (p = 0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat (p = 0.001) and body fat mass index (p = 0.002) was lower. Logistic regression analysis showed that TBW percentage > 65.35% (p = 0.050, OR = 3.114) and 3rd space water > 0.95% (p = 0.045, OR = 2.342) were independent risk factors for lower extremity muscle injuries. CONCLUSION: TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training.

9.
Sci Rep ; 14(1): 770, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191602

RESUMO

The characteristics of floor failure and stress changes during the mining process of protective layers are crucial for determining the effectiveness of pressure relief. Three boreholes were designed in the 21104 fully mechanized mining face of Hulusu Coal Mine to implant optical fibers into the floor of the working face. A fiber optic monitoring system was established to monitor the dynamic evolution of stress in the floor rock mass at different mining distances. Based on the information entropy in information theory, the monitoring results in the fiber optic monitoring system are calculated to obtain the stress information entropy at different mining distances. A quantitative dynamic analysis is conducted on the stress change process of the mining floor rock layer, and the stress change law of the protective layer after mining is verified through numerical calculation and similar simulation experiments. The results indicate that the evolution of stress information entropy can be divided into four stages, namely the original rock stress stage, stress concentration stage, stress release stage, and stress recovery stage. The stress information entropy shows a fluctuating upward trend, indicating that coal seam mining leads to a decrease in the orderliness of the overlying rock system and an increase in disorder. In different spatial evolution processes, there are also significant differences in stress information entropy. In the vertical direction, the entropy value of shallow rock layers changes greatly, while the entropy value of deep rock layers changes slightly. Mining leads to a decrease in the orderliness of the entire overlying rock system, an increase in stress information entropy, and a fluctuating upward trend in stress information entropy. The information entropy of overlying rock deformation and re compaction increases, but the degree of change of the former is greater than that of the latter. The Brillouin fiber optic sensing technology provides a new method for monitoring the stress changes in the protective layer mining floor, achieving quantitative analysis of floor rock failure.

10.
Adv Sci (Weinh) ; 11(7): e2306143, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38083984

RESUMO

Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti-inflammatory macrophages, there are few researches on targeting pro-inflammatory macrophages, which is partially attributed to their non-s pecificity phagocytosis of extracellular substances. In this study, a novel recombinant protein is constructed that can be anchored on an exosome membrane with the purpose of targeting pro-inflammatory macrophages via antigen recognition, which is named AnCar-ExoLaIMTS . The data indicate that the phagocytosis efficiencies of pro-inflammatory macrophages for different AnCar-ExoLaIMTS show obvious differences. The AnCar-ExoLaIMTS3 has the best targeting ability for pro-inflammatory macrophages in vitro and in vivo. Mechanically, AnCar-ExoLaIMTS3 can specifically recognize the leucine-rich repeat domain of the TLR4 receptor, and then enter into pro-inflammatory macrophages via the TLR4-mediated receptor endocytosis pathway. Moreover, AnCar-ExoLaIMTS3 can efficiently deliver therapeutic cargo to pro-inflammatory macrophages and inhibit the synovial inflammatory response via downregulation of HIF-1α level, thus ameliorating the severity of arthritis in vivo. Collectively, the work established a novel gene/drug delivery system that can specifically target pro-inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases.


Assuntos
Artrite , Macrófagos , Humanos , Macrófagos/metabolismo , Artrite/tratamento farmacológico , Fagocitose , Anti-Inflamatórios/uso terapêutico , Comunicação Celular
11.
Methods Mol Biol ; 2748: 267-278, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38070119

RESUMO

Chimeric antigen receptor (CAR)-T cell immunotherapy emerges as an effective cancer treatment. However, significant safety concerns remain, such as cytokine release syndrome (CRS) and "on-target, off-tumor" cytotoxicity, due to a lack of precise control over conventional CAR-T cell activity. To address this issue, a nano-optogenetic approach has been developed to enable spatiotemporal control of CAR-T cell activity. This system is comprised of synthetic light-sensitive CAR-T cells and upconversion nanoparticles acting as an in situ nanotransducer, allowing near-infrared light to wirelessly control CAR-T cell immunotherapy.


Assuntos
Neoplasias , Receptores de Antígenos de Linfócitos T , Humanos , Receptores de Antígenos de Linfócitos T/genética , Imunoterapia , Neoplasias/terapia , Optogenética , Linfócitos T , Imunoterapia Adotiva
12.
Artigo em Inglês | MEDLINE | ID: mdl-37931132

RESUMO

Poor interfacial compatibility remains a pressing challenge in the fabrication of high-performance polymer-MOF composites. In response, introducing compatible chemistries such as a carboxylic acid moiety has emerged as a compelling strategy to increase polymer-MOF interactions. In this work, we leveraged compatible functionalities in UiO-66-NH2 and a carboxylic acid-functionalized PIM-1 to fabricate mixed-matrix membranes (MMMs) with improved separation performance compared to PIM-1-based MMMs in industrially relevant conditions. Under pure-gas conditions, PIM-COOH-based MMMs retained selectivity with increasing MOF loading and showed increased permeability due to increased diffusion. The composites were further investigated under industrially relevant conditions, including CO2/N2, CO2/CH4, and H2S/CO2/CH4 mixtures, to elucidate the effects of competitive sorption and plasticization. Incorporation of UiO-66-NH2 in PIM-COOH and PIM-1 mitigated the effects of CO2- and H2S-induced plasticization typically observed in linear polymers. In CO2-based binary mixed-gas tests, all samples showed similar performance as that in pure-gas tests, with minimal competitive sorption contributions associated with the amine functional groups of the MOF. In ternary mixed-gas tests, improved plasticization resistance and interfacial compatibility resulted in PIM-COOH-based MMMs having the highest H2S/CH4 and CO2/CH4 selectivity combinations among the films tested in this study. These findings demonstrate that selecting MOFs and polymers with compatible functional groups is a useful strategy in developing high-performing microporous MMMs that require stability under complex and industrially relevant conditions.

13.
Nano Lett ; 23(23): 11019-11025, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-37988451

RESUMO

The demand for high-speed and low-loss interconnects in modern computer architectures is difficult to satisfy by using traditional Si-based electronics. Although optical interconnects offer a promising solution owing to their high bandwidth, low energy dissipation, and high-speed processing, integrating elements such as a light source, detector, and modulator, comprising different materials with optical waveguides, presents many challenges in an integrated platform. Two-dimensional (2D) van der Waals (vdW) semiconductors have attracted considerable attention in vertically stackable optoelectronics and advanced flexible photonics. In this study, optoelectronic components for exciton-based photonic circuits are demonstrated by integrating lithographically patterned poly(methyl methacrylate) (PMMA) waveguides on 2D vdW devices. The excitonic signals generated from the 2D materials by using laser excitation were transmitted through patterned PMMA waveguides. By introducing an external electric field and combining vdW heterostructures, an excitonic switch, phototransistor, and guided-light photovoltaic device on SiO2/Si substrates were demonstrated.

14.
Bioengineering (Basel) ; 10(10)2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37892925

RESUMO

The liver is one of the key organs for exogenous and endogenous metabolism and is often a target for drug- and chemical-driven toxicity. A wide range of experimental approaches has been established to model and characterize the mechanisms of drug- and chemical-induced hepatotoxicity. A number of microfluidics-enabled in vitro models of the liver have been developed, but the unclear translatability of these platforms has hindered their adoption by the pharmaceutical industry; to achieve wide use for drug and chemical safety evaluation, demonstration of reproducibility and robustness under various contexts of use is required. One of these commercially available platforms is the PhysioMimix LC12, a microfluidic device where cells are seeded into a 3D scaffold that is continuously perfused with recirculating cell culture media to mimic liver sinusoids. Previous studies demonstrated this model's functionality and potential applicability to preclinical drug development. However, to gain confidence in PhysioMimix LC12's robustness and reproducibility, supplementary characterization steps are needed, including the assessment of various human hepatocyte sources, contribution of non-parenchymal cells (NPCs), and comparison to other models. In this study, we performed replicate studies averaging 14 days with either primary human hepatocytes (PHHs) or induced pluripotent stem cell (iPSC)-derived hepatocytes, with and without NPCs. Albumin and urea secretion, lactate dehydrogenase, CYP3A4 activity, and metabolism were evaluated to assess basal function and metabolic capacity. Model performance was characterized by different cell combinations under intra- and inter-experimental replication and compared to multi-well plates and other liver platforms. PhysioMimix LC12 demonstrated the highest metabolic function with PHHs, with or without THP-1 or Kupffer cells, for up to 10-14 days. iPSC-derived hepatocytes and PHHs co-cultured with additional NPCs demonstrated sub-optimal performance. Power analyses based on replicate experiments and different contexts of use will inform future study designs due to the limited throughput and high cell demand. Overall, this study describes a workflow for independent testing of a complex microphysiological system for specific contexts of use, which may increase end-user adoption in drug development.

15.
Res Sq ; 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37886581

RESUMO

Background: Single cell RNA sequencing technology (scRNA-seq) has been proven useful in understanding cell-specific disease mechanisms. However, identifying genes of interest remains a key challenge. Pseudo-bulk methods that pool scRNA-seq counts in the same biological replicates have been commonly used to identify differentially expressed genes. However, such methods may lack power due to the limited sample size of scRNA-seq datasets, which can be prohibitively expensive. Results: Motivated by this, we proposed to use the Bayesian-frequentist hybrid (BFH) framework to increase the power. Conclusion: In our idiopathic pulmonary fibrosis (IPF) case study, we demonstrated that with a proper informative prior, the BFH approach identified more genes of interest. Furthermore, these genes were reasonable based on the current knowledge of IPF. Thus, the BFH offers a unique and flexible framework for future scRNA-seq analyses.

16.
BMC Health Serv Res ; 23(1): 1116, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37853393

RESUMO

BACKGROUND: The trend of Type 2 diabetes-related costs over 4 years could be classified into different groups. Patient demographics, clinical factors (e.g., A1C, short- and long-term complications), and rurality could be associated with different trends of cost. Study objectives are to: (1) understand the trajectories of cost in different groups; (2) investigate the relationship between cost and key factors in each cost trajectory group; and (3) assess significant factors associated with different cost trajectories. METHODS: Commercial claims data in Texas from 2016 to 2019 were provided by a large commercial insurer and were analyzed using group-based trajectory analysis, longitudinal analysis of cost, and logistic regression analyses of different trends of cost. RESULTS: Five groups of distinct trends of Type 2 diabetes-related cost were identified. Close to 20% of patients had an increasing cost trend over the 4 years. High A1C values, diabetes complications, and other comorbidities were significantly associated with higher Type 2 diabetes costs and higher chances of increasing trend over time. Rurality was significantly associated with higher chances of increasing trend over time. CONCLUSIONS: Group-based trajectory analysis revealed distinct patient groups with increased cost and stable cost at low, medium, and high levels in the 4-year period. The significant associations found between the trend of cost and A1C, complications, and rurality have important policy and program implications for potentially improving health outcomes and constraining healthcare costs.


Assuntos
Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Seguro , Humanos , Texas/epidemiologia , Hemoglobinas Glicadas
17.
Oncol Nurs Forum ; 50(6): 679-691, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37874753

RESUMO

OBJECTIVES: To examine associations between a history of adverse childhood experiences (ACEs) and receiving preventive cervical cancer screening and to investigate whether number and type of ACE exposures were predictive of cervical cancer screening uptake. SAMPLE & SETTING: Data were from 11,042 adults who completed the 2020 Texas Behavioral Risk Factor Surveillance System survey. The U.S. Preventive Services Task Force guidelines were used to indicate whether individuals had received cervical cancer screening at recommended intervals. METHODS & VARIABLES: Multiple logistic regression analysis was used to predict the likelihood of not having received the recommended preventive cancer screening by number and type of ACE exposures. Chi-square analysis was used to determine associations among demographic characteristics, cancer screening uptake, and ACE number and type. RESULTS: Individuals with one to three ACEs and those with six or more ACEs were statistically more likely not to have received the recommended cervical cancer screenings compared to those with zero ACEs. A history of physical ACEs was associated with 3.88 times the likelihood of not having received the recommended cervical cancer screening. IMPLICATIONS FOR NURSING: To promote timely cervical cancer screening and prevent retraumatization of patients with a history of ACEs, providers should implement trauma-informed care principles in their healthcare settings.


Assuntos
Experiências Adversas da Infância , Neoplasias do Colo do Útero , Adulto , Feminino , Humanos , Detecção Precoce de Câncer , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Inquéritos e Questionários , Sistema de Vigilância de Fator de Risco Comportamental
18.
BMC Health Serv Res ; 23(1): 1083, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821934

RESUMO

BACKGROUND: Pembrolizumab is superior to chemotherapy as a first-line treatment for patients with mismatch-repair-deficient (dMMR) or microsatellite-instability-high (MSI-H) advanced or metastatic colorectal cancer (CRC), with a significant long-term survival benefit according to the KEYNOTE-177 trial. The current study aimed to determine whether pembrolizumab is a cost-effective treatment for patients with dMMR/MSI-H advanced or metastatic CRC in China. METHODS: A partitioned survival model (PSM) was developed to simulate patients with dMMR/MSI-H advanced or metastatic CRC based on progression-free survival (PFS), progressive disease (PD) and death. The model was designed using a lifetime horizon, a 6-week cycle, and a 5% discount rate. The patients in the model had metastatic dMMR/MSI-H CRC and had not previously received treatment; these characteristics were similar to those of patients in KEYNOTE-177, a phase 3, open-label randomized clinical trial. The health outcomes and utilities were based on the KEYNOTE-177 trial and published data, respectively. Costs were calculated based on local charges (2022) and published literature. A treatment was deemed cost-effective in China if the incremental cost-effectiveness ratio (ICER) value was less than U.S.$38,142.56 per quality-adjusted life-year (QALY). The robustness of the results was assessed via one-way deterministic and probabilistic sensitivity analyses. RESULTS: Baseline analysis revealed that pembrolizumab provided an additional 2.58 QALYs (3.00 life-year) at an incremental cost of U.S.$78,286.04, resulting in an ICER of U.S.$30,330.15 per QALY, which was below the willingness-to-pay threshold of U.S.$38,142.56 per QALY. When the patient assistance program (PAP) was considered, the ICER became U.S.$1,730.67 per QALY, manifesting absolute cost-effectiveness. The results of sensitivity analyses demonstrated that pembrolizumab was cost-effective in most cases. CONCLUSIONS: Pembrolizumab is a cost-effective first-line treatment for dMMR/MSI-H advanced or metastatic CRC patients in China, especially considering the PAP.


Assuntos
Antineoplásicos Imunológicos , Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Análise de Custo-Efetividade , Antineoplásicos Imunológicos/uso terapêutico , Análise Custo-Benefício , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Repetições de Microssatélites , Anos de Vida Ajustados por Qualidade de Vida
19.
Science ; 382(6667): 202-206, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37824644

RESUMO

Existing polyamide (PA) membrane synthesis protocols are underpinned by controlling diffusion-dominant liquid-phase reactions that yield subpar spatial architectures and ionization behavior. We report an ice-confined interfacial polymerization strategy to enable the effective kinetic control of the interfacial reaction and thermodynamic manipulation of the hexagonal polytype (Ih) ice phase containing monomers to rationally synthesize a three-dimensional quasilayered PA membrane for nanofiltration. Experiments and molecular simulations confirmed the underlying membrane formation mechanism. Our ice-confined PA nanofiltration membrane features high-density ionized structure and exceptional transport channels, realizing superior water permeance and excellent ion selectivity.

20.
World J Surg Oncol ; 21(1): 306, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37749564

RESUMO

OBJECTIVE: To investigate the relationship between dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) measurements and the potential composition of rectal carcinoma. METHODS: Twenty-four patients provided informed consent for this study. DCE-MRI was performed before total mesorectal excision. Quantitative parameters were calculated based on a modified Tofts model. Whole-mount immunohistochemistry and Masson staining sections were generated and digitized at histological resolution. The percentage of tissue components area was measured. Pearson correlation analysis was used to evaluate the correlations between pathological parameters and DCE-MRI parameters. RESULTS: On the World Health Organization (WHO) grading scale, there were significant differences in extracellular extravascular space (Ktrans) (F = 9.890, P = 0.001), mean transit time (MTT) (F = 9.890, P = 0.038), CDX-2 (F = 4.935, P = 0.018), and Ki-67 (F = 4.131, P = 0.031) among G1, G2, and G3. ECV showed significant differences in extramural venous invasion (t = - 2.113, P = 0.046). Ktrans was strongly positively correlated with CD34 (r = 0.708, P = 0.000) and moderately positively correlated with vimentin (r = 0.450, P = 0.027). Interstitial volume (Ve) was moderately positively correlated with Masson's (r = 0.548, P = 0.006) and vimentin (r = 0.417, P = 0.043). There was a moderate negative correlation between Ve and CDX-2 (r = - 0.441, P = 0.031). The rate constant from extracellular extravascular space to blood plasma (Kep) showed a strong positive correlation with CD34 expression (r = 0.622, P = 0.001). ECV showed a moderate negative correlation with CDX-2 (r = - 0.472, P = 0.020) and a moderate positive correlation with collagen fibers (r = 0.558, P = 0.005). CONCLUSION: The dynamic contrast-enhanced MRI-derived parameters measured in rectal cancer were significantly correlated with the proportion of histological components. This may serve as an optimal imaging biomarker to identify tumor tissue components.


Assuntos
Carcinoma , Neoplasias Retais , Humanos , Vimentina , Meios de Contraste , Imageamento por Ressonância Magnética/métodos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/cirurgia
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