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1.
Abdom Radiol (NY) ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38977489

RESUMO

BACKGROUND: Although systemic therapies are recommended for hepatocellular carcinoma (HCC) patients with main portal vein (MPV) invasion and preserved liver function, the outcome is limited. In the real-world, chemoembolization is a commonly used local treatment for advanced HCC. PURPOSE: To evaluate whether the additional chemoembolization treatment yields survival benefits compared to systemic therapy for HCC patients with MPV invasion and preserved liver function (Child-Pugh score ≤ B7) in a real-world study from multiple centers. PATIENTS AND METHODS: Between January 2020 and December 2022, 91 consecutive HCC patients with MPV invasion who received either systemic medical therapy (i.e., tyrosine kinase inhibitors (TKIs) plus anti-PD-1 immunotherapy, S group, n = 43) or in combination with chemoembolization treatment (S-T group, n = 48) from five centers were enrolled in the study. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and treatment response. Adverse events (AEs) related to treatment were also recorded. Survival curves were constructed with the Kaplan-Meier method and compared using the log-rank test. RESULTS: The baseline characteristics were comparable between the two groups. The mean number of chemoembolization sessions per patient was 2.1 (range 1-3). The median OS was 10.0 months and 8.0 months in the S-T group and S group, respectively (P = 0.254). The median PFS between the two groups was similar (4.0 months vs. 4.0 months, P = 0.404). The disease control rate between the S-T and S groups were comparable (60.4% vs. 62.8%, P = 0.816). Although no chemoembolization-related deaths occurred, 13 grade 3-4 AEs occurred in the S-T group. CONCLUSIONS: The results of the real-world study demonstrated that additional chemoembolization treatment did not yield survival benefits compared to TKIs plus anti-PD-1 immunotherapy for the overall patients with advanced HCC and MPV invasion.

2.
Helicobacter ; 29(4): e13114, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39031966

RESUMO

BACKGROUND: Patient adherence status to the newly introduced family-based Helicobacter pylori (H. pylori) infection control and management strategy remains unclear, so are its influencing factors. We aim to investigate family members' adherence and its influencing factors during the family-based H. pylori infection management practice for related disease prevention. MATERIALS AND METHODS: Based on our previously family-based H. pylori survey in 2021, 282 families including 772 individuals were followed up 2 years after the initial survey to compare if the investigation and education might improve family member's adherence. The participant's adherence to H. pylori infection awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were followed up, and their influencing factors were also analyzed. RESULTS: The overall participant's adherence to recommendations on H. pylori awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were 77% (187/243), 67.3% (138/205), 60.1% (211/351), 46.5% (107/230), 45.6% (159/349), and 39.1% (213/545), respectively; and all showed improvements compared with their prior survey stages. The top reasons for rejection to treatment, retest, and gastroscopy were forgetting or unaware of H. pylori infection (30.3%), busy (32.8%), and asymptomatic (67.9%), respectively. Independent risk factor for low adherence to treatment was occupation (e.g., staff: OR 4.49, 95% CI 1.34-15.10). Independent favorable factors for treatment adherence were individuals at the ages of 18-44 years (OR 0.19, 95% CI 0.04-0.89) and had a large family size (e.g., four family members: OR 0.15, 95% CI 0.06-0.41); for retest adherence, it was individuals at the ages of 60-69 years (OR 0.23, 95% CI 0.06-0.97); for gastroscopy adherence, it was individuals at the age of 60-69 years (OR 0.46, 95% CI 0.28-0.75), and with gastrointestinal symptoms (OR 0.57, 95% CI 0.36-0.90). CONCLUSIONS: Family-based H. pylori management increases individual adherence to treatment, retest, and awareness, and there are also improved adherence to gastroscopy, publicity, and personal hygiene recommendations; further efforts are required to enhance the individual adherence rate for related disease prevention.


Assuntos
Família , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , China/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Cooperação do Paciente/estatística & dados numéricos , Idoso , Inquéritos e Questionários , Controle de Infecções/métodos , Criança
3.
Helicobacter ; 29(3): e13063, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38874128

RESUMO

BACKGROUND: The overall benefits of the newly introduced family-based Helicobacter pylori (H. pylori) infection control and management (FBCM) and screen-and-treat strategies in preventing multiple upper gastrointestinal diseases at national level in China have not been explored. We investigate the cost-effectiveness of these strategies in the whole Chinese population. MATERIALS AND METHODS: Decision trees and Markov models of H. pylori infection-related non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), and gastric cancer (GC) were developed to simulate the cost-effectiveness of these strategies in the whole 494 million households in China. The main outcomes include cost-effectiveness, life years (LY), quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER). RESULTS: When compared with no-screen strategy, both FBCM and screen-and-treat strategies reduced the number of new cases of NUD, PUD, PUD-related deaths, and the prevalence of GC, and cancer-related deaths. The costs saved by these two strategies were $1467 million and $879 million, quality-adjusted life years gained were 227 million and 267 million, and life years gained were 59 million and 69 million, respectively. Cost-effectiveness analysis showed that FBCM strategy costs -$6.46/QALY and -$24.75/LY, and screen-and-treat strategy costs -$3.3/QALY and -$12.71/LY when compared with no-screen strategy. Compared to the FBCM strategy, the screen-and-treat strategy reduced the incidence of H. pylori-related diseases, added 40 million QALYs, and saved 10 million LYs, but at the increased cost of $588 million. Cost-effectiveness analysis showed that screen-and-treat strategy costs $14.88/QALY and $59.5/LY when compared with FBCM strategy. The robustness of the results was also verified. CONCLUSIONS: Both FBCM and screen-and-treat strategies are highly cost-effective in preventing NUD, PUD, and GC than the no-screen strategy in Chinese families at national level. As FBCM strategy is more practical and efficient, it is expected to play a more important role in preventing familial H. pylori infection and also serves as an excellent reference for other highly infected societies.


Assuntos
Análise Custo-Benefício , Infecções por Helicobacter , Humanos , Infecções por Helicobacter/economia , Infecções por Helicobacter/prevenção & controle , Infecções por Helicobacter/diagnóstico , China/epidemiologia , Helicobacter pylori , Anos de Vida Ajustados por Qualidade de Vida , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/prevenção & controle , Neoplasias Gástricas/economia , Feminino , Programas de Rastreamento/economia , Adulto , Gastroenteropatias/microbiologia , Gastroenteropatias/prevenção & controle , Gastroenteropatias/economia , Idoso , Controle de Infecções/economia , Controle de Infecções/métodos , Úlcera Péptica/prevenção & controle , Úlcera Péptica/economia , População do Leste Asiático
4.
J Gastroenterol ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38814335

RESUMO

BACKGROUND: Little information is available regarding global H. pylori recurrence, recrudescence, and re-infection in pediatric patients after successful eradication, nor are their influencing factors clear. We conducted a systematic review and meta-analysis to determine global H. pylori recurrence status and its influencing factors in children and adolescents to improve infection management and disease prevention. METHODS: Published studies on H. pylori recurrence in children and adolescents were collected from major public databases until January 2023. H. pylori recurrences were determined using randomized-effect and fixed-effect models. Stratified analysis was performed based on various regions, countries, publication time, human development indexes (HDIs), and ages. RESULTS: A total of 3310 relevant articles were screened, and 30 articles (1915 participants) were finally enrolled for analysis. The overall H. pylori recurrence rate was 19%, and the annual recurrence rate was 13%. In stratified analysis, H. pylori annual recurrence rate in Asian children was higher than that in Europe (17% vs. 6%) and higher in developing countries than in developed countries (18% vs. 5%). In children aged ≤ 5 years, ≤ 10 years, and 11-18 years, the H. pylori recurrence rates were 30%, 14%, and 8%, respectively. H. pylori recrudescence and re-infection rates were 6% and 10%, respectively, and its recurrence was inversely correlated with HDI. CONCLUSIONS: These results provide insights into global H. pylori recurrence, annual recurrence, recrudescence, and re-infection status in pediatric population. The stratified analysis revealed the pattern and seriousness of infection, which requires further efforts to improve patient care.

6.
Sensors (Basel) ; 24(4)2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38400339

RESUMO

A vehicle detection algorithm is an indispensable component of intelligent traffic management and control systems, influencing the efficiency and functionality of the system. In this paper, we propose a lightweight improvement method for the YOLOv5 algorithm based on integrated perceptual attention, with few parameters and high detection accuracy. First, we propose a lightweight module IPA with a Transformer encoder based on integrated perceptual attention, which leads to a reduction in the number of parameters while capturing global dependencies for richer contextual information. Second, we propose a lightweight and efficient multiscale spatial channel reconstruction (MSCCR) module that does not increase parameter and computational complexity and facilitates representative feature learning. Finally, we incorporate the IPA module and the MSCCR module into the YOLOv5s backbone network to reduce model parameters and improve accuracy. The test results show that, compared with the original model, the model parameters decrease by about 9%, the average accuracy (mAP@50) increases by 3.1%, and the FLOPS does not increase.

7.
Drug Metab Dispos ; 52(3): 210-217, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38195521

RESUMO

Valproic acid (VPA) is a first-line antiepileptic drug with broad efficacy. Due to significant individual differences in its metabolism, therapeutic drug monitoring is commonly used. However, the recommended therapeutic range (50-100 µg/mL) is inadequate for predicting clinical outcomes. Additionally, the relationship between VPA metabolites and clinical outcomes remains unclear. In this retrospective study, 485 Chinese Southern Han epilepsy patients receiving VPA monotherapy were analyzed after reaching steady-state levels. Plasma concentrations of VPA and its five main metabolites were determined by liquid chromatography-mass spectrometry (LC-MS). We assessed the relevance of the recommended therapeutic VPA range for clinical outcomes and explored the association between VPA/metabolites levels and treatment efficacy/adverse effects. Vitro experiments were conducted to assess 4-ene-VPA hepatotoxicity. The therapeutic range of VPA exhibited no significant correlation with clinical outcomes, and plasma concentrations of VPA failed to serve as predictive indicators for treatment response/adverse effects. Treatment responders had higher 2-PGA concentrations (median, 26.39 ng/mL versus 13.68 ng/mL), with a threshold of 36.5 ng/mL for optimal epilepsy treatment. Patients with abnormal liver function had a higher 4-ene-VPA median concentration (6.41 µg/mL versus 4.83 µg/mL), and the ratio of 4-ene-VPA to VPA better predicted VPA-induced hepatotoxicity (area under the curve, 0.718) than 4-ene-VPA concentration. Vitro experiments revealed that 4-ene-VPA was more hepatotoxic than VPA in HepaRG and L02 cell lines. Total plasma VPA concentration does not serve as a predictor of clinical outcomes. 2-PGA concentrations may be associated with efficacy, whereas the ratio of 4-ene-VPA to VPA may be considered a better biomarker (threshold 10.03%) for VPA-induced hepatotoxicity. SIGNIFICANCE STATEMENT: This was the first and largest observational cohort in China to explore the relationship between patients' parent and metabolites concentrations of VPA and clinical outcomes during the maintenance of VPA monotherapy in epileptic patients. This study provided feasible references of VPA for epilepsy clinical treatment with a larger sample of patients compared with previous studies for a more definitive conclusion based on real-world situations. We found two potential biomarkers in predicting efficacy and liver injury, respectively. This breakthrough has the potential to assist in the rational use of VPA.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Epilepsia , Humanos , Anticonvulsivantes/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Monitoramento de Medicamentos , Epilepsia/tratamento farmacológico , Estudos Retrospectivos , Ácido Valproico/efeitos adversos
8.
J Hazard Mater ; 465: 133376, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38159518

RESUMO

Deoxynivalenol contamination in feed and food, pervasive from growth, storage, and processing, poses a significant risk to dairy cows, particularly when exposed to a high-starch diet; however, whether a high-starch diet exacerbates these negative effects remains unclear. Therefore, we investigated the combined impact of deoxynivalenol and dietary starch on the production performance, rumen function, and health of dairy cows using metabolomics and 16 S rRNA sequencing. Our findings suggested that both high- and low-starch diets contaminated with deoxynivalenol significantly reduced the concentration of propionate, isobutyrate, valerate, total volatile fatty acids (TVFA), and microbial crude protein (MCP) concentrations, accompanied by a noteworthy increase in NH3-N concentration in vitro and in vivo (P < 0.05). Deoxynivalenol altered the abundance of microbial communities in vivo, notably affecting Oscillospiraceae, Lachnospiraceae, Desulfovibrionaceae, and Selenomonadaceae. Additionally, it significantly downregulated lecithin, arachidonic acid, valine, leucine, isoleucine, arginine, and proline metabolism (P < 0.05). Furthermore, deoxynivalenol triggered oxidative stress, inflammation, and dysregulation in immune system linkage, ultimately compromising the overall health of dairy cows. Collectively, both high- and low-starch diets contaminated with deoxynivalenol could have detrimental effects on rumen function, posing a potential threat to production performance and the overall health of cows. Notably, the negative effects of deoxynivalenol are more pronounced with a high-starch diet than a low-starch diet.


Assuntos
Microbiota , Leite , Tricotecenos , Feminino , Bovinos , Animais , Leite/metabolismo , Lactação/fisiologia , Rúmen/metabolismo , Dieta/veterinária , Amido/metabolismo , Ração Animal/análise , Fermentação
9.
Bioact Mater ; 33: 483-496, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38125638

RESUMO

Limited by low tumor immunogenicity and the immunosuppressive tumor microenvironment (TME), triple-negative breast cancer (TNBC) has been poorly responsive to immunotherapy so far. Herein, a Ca & Mn dual-ion hybrid nanostimulator (CMS) is constructed to enhance anti-tumor immunity through ferroptosis inducing and innate immunity awakening, which can serve as a ferroptosis inducer and immunoadjuvant for TNBC concurrently. On one hand, glutathione (GSH) depletion and reactive oxygen species (ROS) generation can be achieved due to the mixed valence state of Mn in CMS. On the other hand, as an exotic Ca2+ supplier, CMS causes mitochondrial Ca2+ overload, which further amplifies the oxidative stress. Significantly, tumor cells undergo ferroptosis because of the inactivation of glutathione peroxidase 4 (GPX4) and accumulation of lipid peroxidation (LPO). More impressively, CMS can act as an immunoadjuvant to awaken innate immunity by alleviating intra-tumor hypoxia and Mn2+-induced activation of the STING signaling pathway, which promotes polarization of tumor-associated macrophages (TAMs) and activation of dendritic cells (DCs) for antigen presentation and subsequent infiltration of tumor-specific cytotoxic T lymphocytes (CTLs) into tumor tissues. Taken together, this work demonstrates a novel strategy of simultaneously inducing ferroptosis and awakening innate immunity, offering a new perspective for effective tumor immunotherapy of TNBC.

10.
Artigo em Inglês | MEDLINE | ID: mdl-37819817

RESUMO

Camouflaged object detection (COD) aims to identify object pixels visually embedded in the background environment. Existing deep learning methods fail to utilize the context information around different pixels adequately and efficiently. In order to solve this problem, a novel pixel-centric context perception network (PCPNet) is proposed, the core of which is to customize the personalized context of each pixel based on the automatic estimation of its surroundings. Specifically, PCPNet first employs an elegant encoder equipped with the designed vital component generation (VCG) module to obtain a set of compact features rich in low-level spatial and high-level semantic information across multiple subspaces. Then, we present a parameter-free pixel importance estimation (PIE) function based on multiwindow information fusion. Object pixels with complex backgrounds will be assigned with higher PIE values. Subsequently, PIE is utilized to regularize the optimization loss. In this way, the network can pay more attention to those pixels with higher PIE values in the decoding stage. Finally, a local continuity refinement module (LCRM) is used to refine the detection results. Extensive experiments on four COD benchmarks, five salient object detection (SOD) benchmarks, and five polyp segmentation benchmarks demonstrate the superiority of PCPNet with respect to other state-of-the-art methods.

11.
Sci Total Environ ; 897: 165475, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37442472

RESUMO

Coal spontaneous combustion often wastes resources and causes environmental pollution. Rapid and accurate identification of high temperature areas in coal is essential to reducing such combustion and environmental pollution. The acoustic thermometry method has the benefits of large temperature measurement space, non-contact, and high interference resistance. Determining the attenuation characteristics of acoustic waves in loose coal is the basis and premise for realizing acoustic temperature measurement. Four types of bituminous coal were scanned by computer tomography equipment. A self-designed acoustic attenuation test device was used to test coal samples under different temperatures and particle sizes. The study result demonstrates that the distribution characteristics of loose coal voids are mainly related to the particle size. The smaller the particle size range, the more uniform the void distribution. As the size of the coal particles increases, the voids become larger. The acoustic attenuation coefficients of four coal samples showed an increasing trend as frequency increased. The influence of coal particle size distribution on the acoustic attenuation coefficient was greater than that of temperature and metamorphic degree. The peak values of coal sound attenuation for different particle sizes were around 400, 700, 1100, and 1600 Hz. This indicated that the distribution of voids was the main factor affecting the propagation of acoustic waves. By analysing the attenuation mechanism of the acoustic wave in loose coal, the attenuation of acoustic temperature measurement signal was caused by the combined effect of loose coal on acoustic wave absorption and scattering. The study results provide theoretical support for the realization of acoustic wave detection of high temperature point in loose coal spontaneous combustion.

12.
Sci Rep ; 13(1): 8347, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37221282

RESUMO

The eutopic endometrium provides novel insights into endometriotic pathophysiology and treatment. However, no in vivo models currently available are suitable for eutopic endometrium in endometriosis. In this study, we present new endometriotic in vivo models associated with eutopic endometrium using menstrual blood-derived stromal cells (MenSCs). First, we isolated endometriotic MenSCs (E-MenSCs) and healthy MenSCs (H-MenSCs) from the menstrual blood of patients with endometriosis (n = 6) and healthy volunteers (n = 6). Then, we identified MenSCs' endometrial stromal cell properties using adipogenic and osteogenic differentiation. A cell counting kit-8 and wound healing assay were used to compare the proliferation and migration capability between E-MenSCs and H-MenSCs. Seventy female nude mice were used to prepare endometriotic models related to eutopic endometrium by implanting E-MenSCs relying on three approaches, including surgical implantation using scaffolds seeded with MenSCs, and subcutaneous injection of MenSCs in the abdomen and the back (n = 10). H-MenSCs or scaffolds only were implanted in control groups (n = 10). One month after the surgical implantation and 1 week after the subcutaneous injection, we evaluated modeling by hematoxylin-eosin (H&E) and immunofluorescent staining of human leukocyte antigen α (HLAA). Fibroblast morphology, lipid droplets, and calcium nodules in E-MenSCs and H-MenSCs identified their endometrial stromal cell properties. We noticed that the proliferation and migration of E-MenSCs were considerably enhanced compared to H-MenSCs (P < 0.05). E-MenSCs implanted in nude mice formed ectopic lesions using three approaches (n = 10; lesions formation rate: 90%, 115%, and 80%; average volumes: 123.60, 27.37, and 29.56 mm3), while H-MenSCs in the nude mice shaped nothing at the implantation sites. Endometrial glands, stroma, and HLAA expression in these lesions further verified the success and applicability of the proposed endometriotic modeling. Findings provide in vitro and in vivo models and paired controls associated with eutopic endometrium in women with endometriosis using E-MenSCs and H-MenSCs. The approach of subcutaneous injection of MenSCs in the abdomen is highlighted due to non-invasive, simple, and safe steps, a short modeling period (1 week), and an excellent modeling success rate (115%), which could improve the repeats and success of endometriotic nude mice model and shorten the modeling period. These novel models could nearly intimate human eutopic endometrial mesenchymal stromal cells in the progress of endometriosis, opening a new path for disease pathology and treatment.


Assuntos
Endometriose , Animais , Camundongos , Humanos , Feminino , Camundongos Nus , Osteogênese , Células Estromais , Pacientes
14.
IEEE Trans Image Process ; 32: 2267-2278, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37067971

RESUMO

Camouflaged object detection (COD) aims to discover objects that blend in with the background due to similar colors or textures, etc. Existing deep learning methods do not systematically illustrate the key tasks in COD, which seriously hinders the improvement of its performance. In this paper, we introduce the concept of focus areas that represent some regions containing discernable colors or textures, and develop a two-stage focus scanning network for camouflaged object detection. Specifically, a novel encoder-decoder module is first designed to determine a region where the focus areas may appear. In this process, a multi-layer Swin transformer is deployed to encode global context information between the object and the background, and a novel cross-connection decoder is proposed to fuse cross-layer textures or semantics. Then, we utilize the multi-scale dilated convolution to obtain discriminative features with different scales in focus areas. Meanwhile, the dynamic difficulty aware loss is designed to guide the network paying more attention to structural details. Extensive experimental results on the benchmarks, including CAMO, CHAMELEON, COD10K, and NC4K, illustrate that the proposed method performs favorably against other state-of-the-art methods.

15.
Biomolecules ; 13(3)2023 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-36979415

RESUMO

Aberrant expression of G-protein-coupled receptor 158 (GPR158) has been reported to be inextricably linked to a variety of diseases affecting the central nervous system, including Alzheimer's disease (AD), depression, intraocular pressure, and glioma, but the underlying mechanism remains elusive due to a lack of biological and pharmacological tools to elaborate its preferential cellular distribution and molecular interaction network. To assess the cellular localization, expression, and function of GPR158, we generated an epitope-tagged GPR158 mouse model (GPR158Tag) that exhibited normal motor, cognitive, and social behavior, no deficiencies in social memory, and no anxiety-like behavior compared to C57BL/6J control mice at P60. Using immunofluorescence, we found that GPR158+ cells were distributed in several brain regions including the cerebral cortex, hippocampus, cerebellum, and caudate putamen. Next, using the cerebral cortex of the adult GPR158Tag mice as a representative region, we found that GPR158 was only expressed in neurons, and not in microglia, oligodendrocytes, or astrocytes. Remarkably, the majority of GPR158 was enriched in Camk2a+ neurons whilst limited expression was found in PV+ interneurons. Concomitant 3D co-localization analysis revealed that GPR158 was mainly distributed in the postsynaptic membrane, but with a small portion in the presynaptic membrane. Lastly, via mass spectrometry analysis, we identified proteins that may interact with GPR158, and the relevant enrichment pathways were consistent with the immunofluorescence findings. RNA-seq analysis of the cerebral cortex of the GPR158-/- mice showed that GPR158 and its putative interacting proteins are involved in the chloride channel complex and synaptic vesicle membrane composition. Using these GPR158Tag mice, we were able to accurately label GPR158 and uncover its fundamental function in synaptic vesicle function and memory. Thus, this model will be a useful tool for subsequent biological, pharmacological, and electrophysiological studies related to GPR158.


Assuntos
Encéfalo , Receptores Acoplados a Proteínas G , Camundongos , Animais , Camundongos Transgênicos , Camundongos Endogâmicos C57BL , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Encéfalo/metabolismo , Comunicação Celular
16.
J Pharm Pharmacol ; 75(5): 693-702, 2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-36964741

RESUMO

OBJECTIVES: Nephrotic syndrome (NS) remains a therapeutic challenge for nephrologists. Piceatannol-3'-O-ß-d-glucopyranoside (PG) is a major active ingredient in Quzha. The purpose of the study was to assess the renoprotection of PG. METHODS: In vitro, the podocyte protection of PG was assessed in MPC-5. SD rats were injected with adriamycin to induce nephropathy in vivo. The determination of biochemical changes and inflammatory cytokines was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyse expression levels of proteins. KEY FINDINGS: The results showed that PG improved adriamycin-induced podocyte injury, attenuated nephropathy, improved hypoalbuminemia and hyperlipidaemia, and lowered cytokine levels. The podocyte protection of PG was further verified by reduction of desmin and increasing synaptopodin expression. Furthermore, treatment with PG down-regulated the expression of HMGB1, TLR4 and NF-κB along with its upstream regulator, IKKß and yet up-regulated IκBα expression by western blot analysis. CONCLUSIONS: Overall, our data showed that PG has a favourable renoprotection in experimental nephrosis, apparently by amelioration of podocyte injury. PG might mediate these effects via modulation of the HMGB1/TLR4/NF-κB signalling pathway. The study first provides a promising leading compound for the treatment of NS.


Assuntos
Proteína HMGB1 , NF-kappa B , Transdução de Sinais , Animais , Ratos , Citocinas , Doxorrubicina , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Receptor 4 Toll-Like/metabolismo
17.
Gut ; 72(5): 855-869, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36690433

RESUMO

BACKGROUND AND AIMS: Current practice on Helicobacter pylori infection mostly focuses on individual-based care in the community, but family-based H. pylori management has recently been suggested as a better strategy for infection control. However, the family-based H. pylori infection status, risk factors and transmission pattern remain to be elucidated. METHODS: From September 2021 to December 2021, 10 735 families (31 098 individuals) were enrolled from 29 of 31 provinces in mainland China to examine family-based H. pylori infection, related factors and transmission pattern. All family members were required to answer questionnaires and test for H. pylori infection. RESULTS: Among all participants, the average individual-based H. pylori infection rate was 40.66%, with 43.45% for adults and 20.55% for children and adolescents. Family-based infection rates ranged from 50.27% to 85.06% among the 29 provinces, with an average rate of 71.21%. In 28.87% (3099/10 735) of enrolled families, there were no infections; the remaining 71.13% (7636/10 735) of families had 1-7 infected members, and in 19.70% (1504/7636), all members were infected. Among 7961 enrolled couples, 33.21% had no infection, but in 22.99%, both were infected. Childhood infection was significantly associated with parental infection. Independent risk factors for household infection were infected family members (eg, five infected members: OR 2.72, 95% CI 1.86 to 4.00), living in highly infected areas (eg, northwest China: OR 1.83, 95% CI 1.57 to 2.13), and large families in a household (eg, family of three: OR 1.97, 95% CI 1.76 to 2.21). However, family members with higher education and income levels (OR 0.85, 95% CI 0.79 to 0.91), using serving spoons or chopsticks, more generations in a household (eg, three generations: OR 0.79, 95% CI 0.68 to 0.92), and who were younger (OR 0.57, 95% CI 0.46 to 0.70) had lower infection rates (p<0.05). CONCLUSION: Familial H. pylori infection rate is high in general household in China. Exposure to infected family members is likely the major source of its spread. These results provide supporting evidence for the strategic changes from H. pylori individual-based treatment to family-based management, and the notion has important clinical and public health implications for infection control and related disease prevention.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Criança , Adulto , Adolescente , Humanos , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/prevenção & controle , Família , Fatores de Risco , China/epidemiologia , Estudos Epidemiológicos , Prevalência
18.
Histol Histopathol ; 38(9): 1069-1077, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36562285

RESUMO

Qinba selenium mushroom is a mushroom belonging to the Basidiomycetes family, which is believed to have anti- oxidant, anti-tumoral and anti-mutagenic activities. However, the efficacy of Qinba selenium mushroom against multiple myeloma has not been confirmed. The present study aimed to investigate the apoptotic effect of FA-2-b-ß, the selenium mushroom extract from Qinba on multiple myeloma (MM) cells. The MM RPMI-8226 cells were treated with FA-2-b-ß at different concentrations and time points. MM RPMI-8226 cell proliferation and apoptosis were detected by the Cell Counting Kit-8 (CCK-8) assay and Annexin V/propidium iodide (PI) assay, RT-QPCR and western blotting analyses were performed to determine the proteins and pathways involved. The results of the present study demonstrated that FA-2-b-ß has high anti-proliferative activities and strong pro-apoptotic effects on MM RPMI-8226 cells, and its pharmacological effects on proliferation changes occurred in a dose- and time-dependent manner. In addition, we found that FA-2-b-ß was able to induce cell apoptosis and promote cell cycle arrest at G0/G1 phase. In summary, the results illustrate the involvement of FA-2-b-ß in mediating G0/G1 cell cycle arrest and apoptosis in MM RPMI-8226 cells, which suggested that FA-2-b-ß might have therapeutic potential against multiple myeloma as an effective compound, and may provide useful information for the development of a novel therapeutic target in this area.


Assuntos
Agaricales , Mieloma Múltiplo , Selênio , Humanos , Linhagem Celular Tumoral , Selênio/farmacologia , Selênio/uso terapêutico , Proliferação de Células , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Apoptose
19.
Ann Transl Med ; 10(20): 1146, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36388805

RESUMO

Background: Endovascular treatment of abdominal aortic aneurysm (AAA) has been in use for several decades and has become the main treatment for this disease. Iliac branch occlusion (IBO) is a common complication after endovascular treatment. The diagnosis and guidance of contrast-enhanced ultrasound (CEUS) combined with computed tomography angiography (CTA) in the treatment of recurrent IBO after endovascular aneurysm repair (EVAR) are rarely reported. In this case, CEUS gave important hints on the cause of IBO. Case Description: We present a 67-year-old male patient who was diagnosed with AAA in 2020 and underwent endovascular treatment in the same period. There was no family history of AAA. The operation process was successful. The CTA re-examination one month after operation showed that the aneurysm was well isolated without obvious endoleak. However, the patient developed intermittent claudication of both lower limbs after operation, but did not receive relevant diagnosis and treatment. Four months after surgery, the patient's claudication symptoms of the left lower limb were significantly worse than before, and CTA review revealed left IBO. The left ankle brachial index (ABI) was too low to detect the value. A femoral artery thrombectomy was performed and a stent was extended distal to the left iliac stent. The claudication symptoms improved after surgery. Unfortunately, only two months later, the patient developed rest pain in the left lower limb. CTA examination showed that the left iliac branch was occluded again. The problem in the proximal end of the left iliac branch was observed by CEUS before re-operation, which was also confirmed by digital subtraction angiography (DSA) after thrombectomy. The blood flow was significantly improved after the angle of the proximal iliac branch was adjusted by stent placement. The patient did not show claudication symptoms again during follow-up. Through CEUS, we identified the pathogenic causes which could not be reflected in CTA and formulated the correct treatment plan. Conclusions: The risk factors of IBO after EVAR are mostly hidden in the process of the initial operation. CEUS can provide more information about postoperative hemodynamics than CTA. The role of CEUS in postoperative follow-up of endovascular treatment of AAA needs to be further explored.

20.
Micromachines (Basel) ; 13(10)2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36295916

RESUMO

Indium tin oxide (ITO)-based digital microfluidics (DMF) with unique optical and electrical properties are promising in the development of integrated, automatic and portable analytical systems. The fabrication technique using laser direct etching (LDE) on ITO glass has the advantages of being rapid, low cost and convenient. However, the fabrication resolution of LDE limits the minimum line width for patterns on ITO glasses, leading to a related wider lead wire for the actuating electrodes of DMF compared with photolithography. Therefore, the lead wire of electrodes could affect the droplet motion on the digital microfluidic chip due to the increased contact line with the droplet. Herein, we developed a finite element model of a DMF with improved efficiency to investigate the effect of the lead wire. An optimized electrode pattern was then designed based on a theoretical analysis and validated by a simulation, which significantly decreased the deformation of the droplets down to 0.012 mm. The performance of the optimized electrode was also verified in an experiment. The proposed simulation method could be further extended to other DMF systems or applications to provide an efficient approach for the design and optimization of DMF chips.

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