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1.
Neurotoxicology ; 101: 54-67, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38325603

RESUMO

Acute ischemic stroke followed by microglia activation, and the regulation of neuroinflammatory responses after ischemic injury involves microglia polarization. microglia polarization is involved in the regulation of neuroinflammatory responses and ischemic stroke-related brain damage. Thymoquinone (TQ) is an anti-inflammatory agent following ischemic stroke onset. However, the significance of TQ in microglia polarization following acute ischemic stroke is still unclear. We predicted that TQ might have neuroprotective properties by modulating microglia polarization. In this work, we mimicked the clinical signs of acute ischemic stroke using a mouse middle cerebral artery ischemia-reperfusion (I/R) model. It was discovered that TQ treatment decreased I/R-induced infarct volume, cerebral oedema, and promoted neuronal survival, as well as improved the histopathological changes of brain tissue. The sensorimotor function was assessed by the Garica score, foot fault test, and corner test, and it was found that TQ could improve the motor deficits caused by I/R. Secondly, real-time fluorescence quantitative PCR, immuno-fluorescence, ELISA, and western blot were used to detect the expression of M1/M2-specific markers in microglia to explore the role of TQ in the modulation of microglial cell polarization after cerebral ischemia-reperfusion. We found that TQ was able to promote the polarization of microglia with extremely secreted inflammatory factors from M1 type to M2 type. Furthermore, TQ could block the TLR4/NF-κB signaling pathway via Hif-1α activation which subsequently may attenuate microglia differentiation following the cerebral ischemia, establishing a mechanism for the TQ's beneficial effects in the cerebral ischemia-reperfusion model.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38363503

RESUMO

Heterogeneous Fenton oxidation using traditional catalysts with H2O2 for the degradation of 1,4-dioxane (1,4-DX) still presents challenge. In this study, we explored the potential of Fe-ZSM-5 zeolites (Fe-zeolite) with three Si/Al ratios (25, 100, 300) as heterogeneous Fenton catalysts for the removal of 1,4-DX from aqueous solution. Fe2O3 or ZSM-5 alone provided ineffective in degrading 1,4-DX when combined with H2O2. However, the efficient removal of 1,4-DX using H2O2 was observed when Fe2O3 was loaded on ZSM-5. Notably, the Brønsted acid sites of Fe-zeolite played a crucial role during the degradation of 1,4-DX. Fe-zeolites, in combination with H2O2, effectively removed 1,4-DX via a combination of adsorption and oxidation. Initially, Fe-zeolites demonstrated excellent affinity for 1,4-DX, achieving adsorption equilibrium rapidly in about 10 min, followed by effective catalytic oxidative degradation. Among the Fe-ZSM-5 catalysts, Fe-ZSM-5 (25) exhibited the highest catalytic activity and degraded 1,4-DX the fastest. We identified hydroxyl radicals (·OH) and singlet oxygen (1O2) as the primary reactive oxygen species (ROS) responsible for 1,4-DX degradation, with superoxide anions (HO2·/O2·-) mainly converting into 1O2 and ·OH. The degradation primarily occurred at the Fe-zeolite interface, with the degradation rate constants proportional to the amount of Brønsted acid sites on the Fe-zeolite. Fe-zeolites were effective over a wide working pH range, with alkaline pH conditions favoring 1,4-DX degradation. Overall, our study provides valuable insights into the selection of suitable catalysts for effective removal of 1,4-DX using a heterogeneous Fenton technology.

3.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(1): 138-143, 2024 Feb 18.
Artigo em Chinês | MEDLINE | ID: mdl-38318908

RESUMO

OBJECTIVE: To observe the clinical efficacy of pulpotomy in patients of different ages and to explore the occurrence and characteristics of pulpal calcification. METHODS: A total of 77 patients who underwent pulpotomy for mature permanent premolars and molars with caries-derived pulp exposure in the Department of General Dentistry, Peking University School and Hospital of Stomatology from October 2019 to August 2022 were selected. Pulpotomies were performed in a single visit using iRoot BP Plus bioceramic material as pulp capping agent. The patients were divided into three groups according to age: 25 cases in the adolescent group (11-20 years old) with a mean age of (15.88±2.19) years; 27 cases in the middle-aged group (21-50 years old) with a mean age of (34.59±8.67) years; and 25 cases in the elder-aged group (51-83 years old) with a mean age of (63.84±7.40) years. The patients were reviewed 1 year after the operation to evaluate the clinical efficacy and to record the formation of calcified bridge, thickness of calcified bridge, and pulp calcification index (PCI). RESULTS: There was no statistically significant difference between the three groups in terms of gender, dentition, and tooth position (P > 0.05). The 1-year postoperative follow-up rate was 85.71% (66/77), including 88.00% (22/25) in the adolescent group, 85.19% (23/27) in the middle-aged group, and 84.00% (21/25) in the elder-aged group. The 1-year follow-up clinical success rates of the three groups were 95.45% (21/22), 91.30% (21/23), and 95.24% (20/21), respectively, with no statistically significant difference (P>0.05). Among the clinical success cases, calcified bridges appeared in 12 cases (57.14%, 12/21) in the adolescent group, 8 cases (38.10%, 8/21) in the middle-aged group, and 3 cases (15.00%, 3/20) in the elder-aged group, with statistically significant differences (χ2= 7.810, P = 0.020 < 0.05). The difference was statistically significant (F = 4.434, P = 0.020 < 0.05) when comparing the thickness of calcified bridges among the three groups. Calcified bridge thickness was negatively correlated with age (r = -0.516, P < 0.05). The changes in pulpal calcification index ΔPCI were 0.67 ± 0.58, 0.43 ± 0.51, and 0.25 ± 0.52, respectively, with statistically significant differences among the three groups (F = 3.404, P = 0.040 < 0.05). CONCLUSION: Pulpotomy for caries-derived pulp exposure in elderly patients could also achieve a high success rate. The incidence of calcified bri-dges after pulpotomy and the acceleration of pulpal calcification were age-related. The adolescent group was more likely to form calcified bridges and also showed more pronounced accelerated root canal calcification.


Assuntos
Pulpotomia , Radiologia , Pessoa de Meia-Idade , Idoso , Adolescente , Humanos , Adulto , Criança , Adulto Jovem , Idoso de 80 Anos ou mais , Silicatos , Dentição Permanente , Tratamento do Canal Radicular , Resultado do Tratamento , Óxidos , Compostos de Cálcio , Combinação de Medicamentos
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(1): 95-100, 2024 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-38322541

RESUMO

Disease control priority (DCP) is an important public health intervention strategy. Diseases that should be prioritized for prevention and control are first screened with a series of criteria, including the severity of the disease burden, the effectiveness of disease control technologies, the prevention and control capacity of the existing health system, etc. Then, the prevention and control technologies for these diseases undergo qualitative evaluation (eg, face-to-face interviews, expert consultation, workshops, etc) and quantitative evaluation (eg, cost-benefit analysis, multi-criteria decision analysis, etc). Finally, the public health initiatives that should be prioritized are identified. From the conception of the idea, to the formal proposition of the concept, to guidance for practice, DCP has gone through more than 70 years of development. Through DCP, significant contributions has been made to improving the efficiency of health care service systems and promoting the health of populations in developing countries. Herein, we systematically reviewed the background, development history, realization method, and practical applications of DCP, focusing on exploring the application potential of DCP in health governance and providing technical support and decision-making reference for the comprehensive promotion of the Healthy China Initiative.


Assuntos
Prioridades em Saúde , Saúde Pública , Nível de Saúde , China
5.
FASEB J ; 38(4): e23477, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38334424

RESUMO

Liver transplantation (LT) is the only effective method to treat end-stage liver disease. Hepatic ischemia-reperfusion injury (IRI) continues to limit the prognosis of patients receiving LT. Histone deacetylase 6 (HDAC6) is a unique HDAC member involved in inflammation and apoptosis. However, its role and mechanism in hepatic IRI have not yet been reported. We examined HDAC6 levels in liver tissue from LT patients, mice challenged with liver IRI, and hepatocytes subjected to hypoxia/reoxygenation (H/R). In addition, HDAC6 global-knockout (HDAC6-KO) mice, adeno-associated virus-mediated liver-specific HDAC6 overexpressing (HDAC6-LTG) mice, and their corresponding controls were used to construct hepatic IRI models. Hepatic histology, inflammatory responses, and apoptosis were detected to assess liver injury. The molecular mechanisms of HDAC6 in hepatic IRI were explored in vivo and in vitro. Moreover, the HDAC6-selective inhibitor tubastatin A was used to detect the therapeutic effect of HDAC6 on liver IRI. Together, our results showed that HDAC6 expression was significantly upregulated in liver tissue from LT patients, mice subjected to hepatic I/R surgery, and hepatocytes challenged by hypoxia/reoxygenation (H/R) treatment. Compared with control mice, HDAC6 deficiency mitigated liver IRI by inhibiting inflammatory responses and apoptosis, whereas HDAC6-LTG mice displayed the opposite phenotype. Further molecular experiments show that HDAC6 bound to and deacetylated AKT and HDAC6 deficiency improved liver IRI by activating PI3K/AKT/mTOR signaling. In conclusion, HDAC6 is a key mediator of hepatic IRI that functions to promote inflammation and apoptosis via PI3K/AKT/mTOR signaling. Targeting hepatic HDAC6 inhibition may be a promising approach to attenuate liver IRI.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Traumatismo por Reperfusão , Animais , Humanos , Camundongos , Apoptose , Desacetilase 6 de Histona/metabolismo , Hipóxia/metabolismo , Inflamação/metabolismo , Isquemia/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão/metabolismo , Serina-Treonina Quinases TOR/metabolismo
6.
JAMA Netw Open ; 7(2): e2354277, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38300619

RESUMO

Importance: Evidence regarding the effect of dietary niacin intake on the risk of mortality among patients with nonalcoholic fatty liver disease (NAFLD) is scarce. Objective: To examine the association of dietary niacin intake with all-cause mortality and cardiovascular disease (CVD) mortality among individuals with NAFLD. Design, Setting, and Participants: This cohort study used data from the National Health and Nutrition Examination Survey (2003-2018). In total, 4315 adults aged 20 years or older with NAFLD were included, with NAFLD defined using the United States Fatty Liver Index. Exposure: Dietary niacin intake levels. Main Outcomes and Measures: Weighted Cox proportional hazards models and restricted cubic splines were used to estimate hazard ratios and 95% CIs for all-cause and CVD mortality. Data were analyzed March 1 to September 1, 2023. Results: This cohort study included data from 4315 participants in the analysis (mean [SD] age, 52.5 [16.2] years; 1670 participants ≥60 years [weighted, 30.9%]; 2351 men [weighted, 55.0%]). During a median (IQR) follow-up of 8.8 (4.6-11.8) years, 566 deaths were recorded, of which 197 were attributed to CVD. Compared with participants with a niacin intake of 18.4 mg or lower (the lowest tertile), the multivariable-adjusted hazard ratios for participants with a niacin intake of 26.7 mg or higher (the highest tertile) were 0.70 (95% CI, 0.50-0.96) for all-cause mortality (P = .03 for trend) and 0.65 (95% CI, 0.35-1.20) for CVD mortality (P = .16 for trend). Conclusions and Relevance: Findings from this cohort study suggest that higher dietary niacin intake may be associated with lower risk of all-cause mortality among individuals with NAFLD. There was no evident inverse association between dietary niacin intake and the risk of CVD mortality.


Assuntos
Doenças Cardiovasculares , Niacina , Hepatopatia Gordurosa não Alcoólica , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Inquéritos Nutricionais
7.
J Fluoresc ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329605

RESUMO

In this study, a novel dinuclear lanthanide complex, denoted as [Ho2(L)2(acac)2(CH3OH)2]·CH3OH (1) (where H2L is 2-[((4-methyl)-2-(carboxyl)-imino)]methyl]-8-hydroxyquinoline, and Hacac is acetylacetonate), was successfully synthesized and characterized using single-crystal and elemental analysis, with the auxiliary ligand ß-diketonate and the 8-hydroxyquinoline Schiff base derivative serving as the foundation. Through ligand-to-metal charge transfer, Compound 1 demonstrated remarkable green fluorescence properties, showcasing potential applications in green fluorescence materials and fluorescence sensing. Additionally, Hyaluronic Acid (HA)/Carboxymethyl Chitosan (CMCS) hydrogels were synthesized through a chemical method. Utilizing captopril as a drug model, a novel metal gel granule of captopril was developed and assessed for its inhibitory activity against glioma cells. Molecular docking simulations revealed that only the methanol group in the Ho complex could contribute a polar atom for the formation of binding interactions.

8.
BMC Oral Health ; 24(1): 172, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308269

RESUMO

BACKGROUND: The range of mandibular invasion by a tumour needs to be determined accurately to minimize unnecessary damage to the mandible. This study aimed to compare tumour boundary lines on computed tomography/magnetic resonance (CT/MR) images with those from pathological findings during the preoperative assessment of mandibular invasion by oral squamous cell carcinoma (OSCC). By comparing the methods, the potential of CT/MR for this application could be further elucidated. METHODS: Eight patients with OSCC were imaged with CT/MR, mandibular specimens were collected, and the material site was measured. Haematoxylin-eosin staining was used for histopathological assessment. The presence and boundaries of bone invasion were evaluated. The CT/MR and histopathological boundaries of bone invasion were delineated and merged to compare and calculate the deviation of CT/MR and histopathological boundaries using the Fréchet distance. RESULTS: The mean Fréchet distance between the CT and pathological tumour boundaries was 2.69 mm (standard error 0.46 mm), with a minimum of 1.18 mm, maximum of 3.64 mm, median of 3.10 mm, and 95% confidence interval of 1.40-3.97 mm. The mean Fréchet distance between the tumour boundaries on the MR and pathological images was 3.07 mm (standard error 0.56 mm), with a minimum of 1.53 mm, maximum of 4.74 mm, median of 2.90 mm, and 95% confidence interval of 1.53-4.61 mm. CONCLUSIONS: CT/MR imaging can provide an effective preoperative assessment of mandibular invasion of OSCC. Pathology images can be positioned on CT/MR scans with the help of computer software to improve the accuracy of the findings. The introduction of the Fréchet distance to compare tumour boundary lines is conducive to computer image diagnosis of tumour invasion of jaw boundaries.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Sensibilidade e Especificidade , Invasividade Neoplásica/diagnóstico por imagem , Invasividade Neoplásica/patologia , Mandíbula/diagnóstico por imagem , Mandíbula/patologia , Tomografia Computadorizada por Raios X , Imageamento por Ressonância Magnética , Neoplasias de Cabeça e Pescoço/patologia
9.
Biomed Chromatogr ; : e5834, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308389

RESUMO

Parkinson's disease (PD) is inseparable from metabolic disorders but lacks assessment of specific metabolite alteration. To explore the sequential metabolic changes in PD progression, we evenly divided 78 C57BL/6 mice (10 weeks) into six groups (one control group and five experimental groups) and collected the hippocampus tissue of mice after treating with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and probenecid (twice a week) at five periods (1, 2, 3, 4, and 5 weeks) for metabolome analysis. Our study identified 567 differentially abundant metabolites (DAMs) (total 4348 metabolites). Compared with controls, 145, 146, 171, 208, and 213 DAMs were obtained from the five experimental groups, respectively. Notably, 40 shared DAMs were present in five experimental groups, of which 22 shared DAMs formed a new metabolic network based on amino acid metabolism. Compared with group W3, 84 DAMs were identified in group W5, including 12 unique DAMs. DAMs in different stages of PD were significantly enriched in amino acid metabolism pathway, lipid metabolism pathway, and ferroptosis pathway. l-Glutamine, spermidine, and l-tryptophan were the key hubs in the whole metabolic process of PD. N-Formyl-l-methionine gradually increased in abundance with PD progression, whereas 5-methylcytosine gradually decreased. The study emphasized the sequential changes in DAMs in PD progression, stimulating subsequent studies.

10.
Biomater Sci ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38390765

RESUMO

The aggregation of amyloid-ß (Aß) is one of the important pathological markers of Alzheimer's disease. Ruthenium(II) complexes have good stability, low cytotoxicity, a high fluorescence quantum yield, and a good Stokes shift as fluorescent probes. Based on this, we constructed a fluorescent probe for in vivo real-time imaging and inhibition of Aß-fibril formation using a complex of Ru polypyridine with organic fluorophores (N,N-dimethylaniline) and hydrophobic peptides (KLVFF). DLS and TEM studies have shown that Ru-YH has an inhibitory effect on the fibrotic aggregation of Aß. Both in vivo and in vitro studies have shown that Ru-WJ and Ru-YH can quickly cross the blood-brain barrier and successfully detect Aß in early (2.5-month old) transgenic mouse models. In summary, we have explored the potential of Ru complex based biological probes for early diagnosis and inhibition of AD.

11.
BMC Med ; 22(1): 42, 2024 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-38281914

RESUMO

BACKGROUND: Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. METHODS: We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA. RESULTS: Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P < 0.001) and more positive programmed death ligand 1 (PD-L1) expression (37.5% vs. 11.9%, P < 0.001) than those with an MSS status. Among patients receiving PD-1 inhibitor-based therapy, those with MSI-H had a longer median overall survival (OS, hazard ratio (HR) = 0.17, P = 0.001) and progression-free survival (PFS, HR = 0.14, P < 0.001) than patients with MSS. Integrating MSI-H and PD-L1 expression status (combined positive score ≥ 5) could distinguish the efficacy of immunotherapy. CONCLUSIONS: MSI-H status was associated with a higher TMB value and more positive PD-L1 expression in CCA tumors. Moreover, in patients with advanced CCA who received PD-1 inhibitor-based immunotherapy, MSI-H and positive PD-L1 expression were associated with improved both OS and PFS. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov on 07/01/2017 (NCT03892577).


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Instabilidade de Microssatélites , Antígeno B7-H1/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Colangiocarcinoma/genética , Colangiocarcinoma/terapia , Mutação , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Intra-Hepáticos/metabolismo , Imunoterapia , Genômica , Biomarcadores Tumorais/genética
12.
JMIR Med Inform ; 12: e48995, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38289643

RESUMO

BACKGROUND: Inpatient falls are a substantial concern for health care providers and are associated with negative outcomes for patients. Automated detection of falls using machine learning (ML) algorithms may aid in improving patient safety and reducing the occurrence of falls. OBJECTIVE: This study aims to develop and evaluate an ML algorithm for inpatient fall detection using multidisciplinary progress record notes and a pretrained Bidirectional Encoder Representation from Transformers (BERT) language model. METHODS: A cohort of 4323 adult patients admitted to 3 acute care hospitals in Calgary, Alberta, Canada from 2016 to 2021 were randomly sampled. Trained reviewers determined falls from patient charts, which were linked to electronic medical records and administrative data. The BERT-based language model was pretrained on clinical notes, and a fall detection algorithm was developed based on a neural network binary classification architecture. RESULTS: To address various use scenarios, we developed 3 different Alberta hospital notes-specific BERT models: a high sensitivity model (sensitivity 97.7, IQR 87.7-99.9), a high positive predictive value model (positive predictive value 85.7, IQR 57.2-98.2), and the high F1-score model (F1=64.4). Our proposed method outperformed 3 classical ML algorithms and an International Classification of Diseases code-based algorithm for fall detection, showing its potential for improved performance in diverse clinical settings. CONCLUSIONS: The developed algorithm provides an automated and accurate method for inpatient fall detection using multidisciplinary progress record notes and a pretrained BERT language model. This method could be implemented in clinical practice to improve patient safety and reduce the occurrence of falls in hospitals.

13.
Comput Methods Programs Biomed ; 244: 107998, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38176330

RESUMO

BACKGROUND AND OBJECTIVE: Estimating the three-dimensional (3D) deformation of the lung is important for accurate dose delivery in radiotherapy and precise surgical guidance in lung surgery navigation. Additional 4D-CT information is often required to eliminate the effect of individual variations and obtain a more accurate estimation of lung deformation. However, this results in increased radiation dose. Therefore, we propose a novel method that estimates lung tissue deformation from depth maps and two CT phases per patient. METHODS: The method models the 3D motion of each voxel as a linear displacement along a direction vector, with a variable amplitude and phase that depend on the voxel location. The direction vector and amplitude are derived from the registration of the CT images at the end-of-exhale (EOE) and the end-of-inhale (EOI) phases. The voxel phase is estimated by a neural network. Coordinate convolution (CoordConv) is used to fuse multimodal data and embed absolute position information. The network takes the front and side views as well as the previous phase views as inputs to enhance accuracy. RESULTS: We evaluate the proposed method on two datasets: DIR-Lab and 4D-Lung, and obtain average errors of 2.11 mm and 1.36 mm, respectively. The method achieves real-time performance of less than 7 ms per frame on a NVIDIA GeForce 2080Ti GPU. CONCLUSION: Compared with previous methods, our method achieves comparable or even better accuracy with less CT phases.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Pulmão/diagnóstico por imagem , Tomografia Computadorizada Quadridimensional/métodos , Redes Neurais de Computação , Tórax , Respiração
14.
Heliyon ; 10(1): e23720, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38226247

RESUMO

Background: Acral melanoma (AM), an aggressive subtype of melanoma with poor prognosis, has been increasingly studied. The present study aims to discuss the current status, hotspots and future directions of AM studies through visualized analysis with bibliometrics and knowledge graph. Method: Publications related to acral melanoma from January 1999 to May 2023 were searched and retrieved from the Web of Science. Data extraction and visualization of the top 10 publications by year of publication, journal, country and core author were performed using R Studio (Version 4.3.0) and Scimago Graphica (Version 1.0.34). Co-reference graphs regarding country/region, organization, author, and keywords, as well as reference collaborative network, co-occurrence network, and references were plotted using VOSviewer (Version 1.6.19) and CiteSpace (Version 6.2.R3). Results: A total of 1387 articles related to AM published in English from 1999 to 2023 were included in the present study. A total of 7499 authors were from 2092 organizations in 50 countries. The articles were published in 356 journals, involving 4131 keywords and 28,200 references. The 1387 articles related to AM had been cited a total of 10,014 times by the time of this study. The result showed that Journal of the American Academy of Dermatology had the largest number of citations and citation rate, with a total of 60 publications having been cited 2191 times. Having the top three productivity institutions in the world, the US is the most productive country in this field, with a total of 361 publications. The authors with the highest number of publications were Guo Jun (n = 43) and Si Lu (n = 38) from Peking University. The keyword burstiness test found that "ipilimumab", "open label", "efficacy" and "nivolumab" appeared most frequently in recent years. The co-cited reference timeline graph showed that the clustering of "advanced melanoma" and "melanocytic lesion" has been a hotspot since 2016. Conclusions: The number of AM-related studies has been increasing. The clinical characteristics and immunotherapy of AM are still key research directions, with the US playing a leading role in this field. This bibliometric analysis found up to 1387 publications, which not only comprehensively and quantitatively reflected the research trends and hotspots, but also provided a theoretical basis for future studies of AM. Researchers can benefit from choosing the right journals and finding potential collaborators or partner institutions.

15.
Adv Sci (Weinh) ; : e2304342, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38229183

RESUMO

Immunotherapy targeting PD-L1 is still ineffective for a wide variety of tumors with high unpredictability. Deploying combined immunotherapy with alternative targeting is practical to overcome this therapeutic resistance. Here, the deficiency of serine-threonine kinase STK24 is observed in tumor cells causing substantial attenuation of tumor growth in murine syngeneic models, a process relying on cytotoxic CD8+ T and NK cells. Mechanistically, STK24 in tumor cells associates with and directly phosphorylates AKT at Thr21, which promotes AKT activation and subsequent PD-L1 induction. Deletion or inhibition of STK24, by contrast, blocks IFN-γ-mediated PD-L1 expression. Various murine models indicate that in vivo silencing of STK24 can significantly enhance the efficacy of the anti-PD-1 blockade strategy. Elevated STK24 levels are observed in patient specimens in multiple tumor types and inversely correlated with intratumoral infiltration of cytotoxic CD8+ T cells and with patient survival. The study collectively identifies STK24 as a critical modulator of antitumor immunity, which engages in AKT and PD-L1/PD-1 signaling and is a promising target for combined immunotherapy.

16.
Clin Transl Oncol ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38194018

RESUMO

BACKGROUND: Lung adenocarcinoma is a common cause of cancer-related deaths worldwide, and accurate EGFR genotyping is crucial for optimal treatment outcomes. Conventional methods for identifying the EGFR genotype have several limitations. Therefore, we proposed a deep learning model using non-invasive CT images to predict EGFR mutation status with robustness and generalizability. METHODS: A total of 525 patients were enrolled at the local hospital to serve as the internal data set for model training and validation. In addition, a cohort of 30 patients from the publicly available Cancer Imaging Archive Data Set was selected for external testing. All patients underwent plain chest CT, and their EGFR mutation status labels were categorized as either mutant or wild type. The CT images were analyzed using a self-attention-based ViT-B/16 model to predict the EGFR mutation status, and the model's performance was evaluated. To produce an attention map indicating the suspicious locations of EGFR mutations, Grad-CAM was utilized. RESULTS: The ViT deep learning model achieved impressive results, with an accuracy of 0.848, an AUC of 0.868, a sensitivity of 0.924, and a specificity of 0.718 on the validation cohort. Furthermore, in the external test cohort, the model achieved comparable performances, with an accuracy of 0.833, an AUC of 0.885, a sensitivity of 0.900, and a specificity of 0.800. CONCLUSIONS: The ViT model demonstrates a high level of accuracy in predicting the EGFR mutation status of lung adenocarcinoma patients. Moreover, with the aid of attention maps, the model can assist clinicians in making informed clinical decisions.

17.
BMC Med Inform Decis Mak ; 24(1): 3, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167058

RESUMO

BACKGROUND: Precise prediction of esophageal squamous cell carcinoma (ESCC) invasion depth is crucial not only for optimizing treatment plans but also for reducing the need for invasive procedures, consequently lowering complications and costs. Despite this, current techniques, which can be invasive and costly, struggle with achieving the necessary precision, highlighting a pressing need for more effective, non-invasive alternatives. METHOD: We developed ResoLSTM-Depth, a deep learning model to distinguish ESCC stages T1-T2 from T3-T4. It integrates ResNet-18 and Long Short-Term Memory (LSTM) networks, leveraging their strengths in spatial and sequential data processing. This method uses arterial phase CT scans from ESCC patients. The dataset was meticulously segmented by an experienced radiologist for effective training and validation. RESULTS: Upon performing five-fold cross-validation, the ResoLSTM-Depth model exhibited commendable performance with an accuracy of 0.857, an AUC of 0.901, a sensitivity of 0.884, and a specificity of 0.828. These results were superior to the ResNet-18 model alone, where the average accuracy is 0.824 and the AUC is 0.879. Attention maps further highlighted influential features for depth prediction, enhancing model interpretability. CONCLUSION: ResoLSTM-Depth is a promising tool for ESCC invasion depth prediction. It offers potential for improvement in the staging and therapeutic planning of ESCC.


Assuntos
Carcinoma de Células Escamosas , Aprendizado Profundo , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas/patologia , Tomografia Computadorizada por Raios X
18.
Nutr Metab (Lond) ; 21(1): 2, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166933

RESUMO

BACKGROUND: Type 1 diabetes is believed to be an autoimmune condition, characterized by destruction of insulin-producing cells, due to the detrimental inflammation in pancreas. Growing evidences have indicated the important role of type I interferon in the development of type 1 diabetes. METHODS: Trex1-deficient rats were generated by using CRISPR-Cas9. The fasting blood glucose level of rat was measured by a Roche Accuchek blood glucose monitor. The levels of insulin, islet autoantibodies, and interferon-ß were measured using enzyme-linked immunosorbent assay. The inflammatory genes were detected by quantitative PCR and RNA-seq. Hematein-eosin staining was used to detect the pathological changes in pancreas, eye and kidney. The pathological features of kidney were also detected by Masson trichrome and periodic acid-Schiff staining. The distribution of islet cells, immune cells or ssDNA in pancreas was analyzed by immunofluorescent staining. RESULTS: In this study, we established a Trex1-deletion Sprague Dawley rat model, and unexpectedly, we found that the Trex1-/- rats spontaneously develop type 1 diabetes. Similar to human diabetes, the hyperglycemia in rats is accompanied by diabetic complications such as diabetic nephropathy and cataract. Mechanistical investigation revealed the accumulation of ssDNA and the excessive production of proinflammatory cytokines, including IFN-ß, in Trex1 null pancreas. These are likely contributing to the inflammation in pancreas and eventually leading to the decline of pancreatic ß cells. CONCLUSIONS: Our study links the DNA-induced chronic inflammation to the pathogenesis of type 1 diabetes, and also provides an animal model for type 1 diabetes studies.

19.
World Neurosurg ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38199460

RESUMO

OBJECTIVE: This investigation aims to evaluate the effectiveness of the paravertebral injection of recombinant human interferon-α2b in conjunction with high-voltage, long-term, pulsed radiofrequency (PRF) in the dorsal root ganglion for the mitigation of postherpetic neuralgia (PHN). METHODS: This retrospective study included 84 individuals with acute PHN. The participants were divided into 3 groups. Group H was treated with interferon-α2b combined with high-voltage long-term PRF. Group C was treated with a combination of high-voltage, long-term PRF and a paravertebral injection (without recombinant human interferon-α2b), and group I was treated with interferon-α2b only. All the patients in the 3 groups were orally administered a 5-mg morphine hydrochloride quick-release tablet when a burst of pain occurred during treatment. The numerical rating scale for pain score, the interleukin-6 and galectin-3 levels, and the incidence of PHN were documented before and after therapy. RESULTS: The pain intensity of all individuals decreased after therapy. Compared with group C, the numerical rating scale scores for group H were significantly reduced at 4, 8, and 12 weeks following therapy, and the PHN incidence was significantly lower. Compared with prior treatment, the recommended dosage of gabapentin capsules and immediate-release morphine hydrochloride tablets was reduced for group H. Compared with group C, the requirement for orally administrated gabapentin capsules and morphine hydrochloride tablets in group H was reduced significantly after treatment. No serious adverse reactions occurred in any of the 3 groups. CONCLUSIONS: Within the context of treatment of acute PHN, the injection of interferon-α2b in conjunction with high-voltage, long-term application of PRF is more effective than PRF or the injection of interferon-α2b alone.

20.
Int J Nurs Pract ; 30(1): e13234, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38273651

RESUMO

OBJECTIVE: The study aimed to explore the influence of Chinese culture and customs on the beliefs and health-related behaviours of Chinese women with gestational diabetes mellitus (GDM). METHODS: This descriptive qualitative study conducted semi-structured interviews with 15 Chinese women between November 2022 and January 2023. The interview data were analysed using thematic analysis. RESULTS: Three major themes are found: (1) beliefs in health, (2) beliefs in illness and GDM and (3) beliefs in health-related behaviours. They worried about the negative effects of GDM on the infant and family, so they actively sought medical advice to maintain health. However, it is challenging for them to balance adhering to healthcare professionals' advice and avoiding practical difficulties in the impact of the Chinese sociocultural context. CONCLUSION: This study emphasizes the influence of Chinese culture and customs on the beliefs and health-related behaviours of women with GDM. Healthcare providers should recognize the influence of Chinese culture, customs and beliefs on women with GDM and their families, in order to provide individualized education to help them maintain health-related behaviours.


Assuntos
Diabetes Gestacional , Gravidez , Feminino , Humanos , Comportamentos Relacionados com a Saúde , Pesquisa Qualitativa , China
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