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2.
J Dermatolog Treat ; 35(1): 2391445, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39191432

RESUMEN

Purpose: Amyopathic dermatomyositis (ADM) is a rare, idiopathic, connective tissue disease and melanoma differentiation-associated protein 5 (MDA5) antibody-positive ADM is more treatment-resistant, especially in patients with interstitial lung disease (ILD). The purpose of this article is to report a case of anti-MDA5-positive ADM successfully treated with JAK inhibitor Upadacitinib.Materials and methods: A 35-year-old Chinese woman presented with recurrent itchy erythema on her face and scalp for 4 years. Upon examination, there were heliotrope erythema and eyelid edema, reddish rash on neck and scalp. Biopsy of the lesions was consistent with DM and a line blot assay confirmed the presence of anti-MDA5 antibodies. This patient was treated with oral Upadacitinib at a dosage of 30 mg daily.Results: After 6 weeks of treatment, she achieved complete clinical remission with no reported side effects or instances of relapse. The antibody titer of anti-MDA5 was also decreased.Conclusions: Upadacitinib may be a potential drug candidate in patients with treatment-resistant ADM, especially in cases with refractory cutaneous conditions.


Asunto(s)
Dermatomiositis , Compuestos Heterocíclicos con 3 Anillos , Helicasa Inducida por Interferón IFIH1 , Humanos , Femenino , Dermatomiositis/tratamiento farmacológico , Dermatomiositis/inmunología , Dermatomiositis/complicaciones , Dermatomiositis/patología , Helicasa Inducida por Interferón IFIH1/inmunología , Adulto , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Resultado del Tratamiento , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/administración & dosificación
3.
4.
Front Oncol ; 14: 1347123, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39184041

RESUMEN

Vessel density within tumor tissues strongly correlates with tumor proliferation and serves as a critical marker for tumor grading. Recognition of vessel density by pathologists is subject to a strong inter-rater bias, thus limiting its prognostic value. There are many challenges in the task of object detection in pathological images, including complex image backgrounds, dense distribution of small targets, and insignificant differences between the features of the target to be detected and the image background. To address these problems and thus help physicians quantify blood vessels in pathology images, we propose Pathological Images-YOLO (PI-YOLO), an enhanced detection network based on YOLOv7. PI-YOLO incorporates the BiFormer attention mechanism, enhancing global feature extraction and accelerating processing for regions with subtle differences. Additionally, it introduces the CARAFE upsampling module, which optimizes feature utilization and information retention for small targets. Furthermore, the GSConv module improves the ELAN module, reducing model parameters and enhancing inference speed while preserving detection accuracy. Experimental results show that our proposed PI-YOLO network has higher detection accuracy compared to Faster-RCNN, SSD, RetinaNet, YOLOv5 network, and the latest YOLOv7 network, with a mAP value of 87.48%, which is 2.83% higher than the original model. We also validated the performance of this network on the ICPR 2012 mitotic dataset with an F1 value of 0.8678, outperforming other methods, demonstrating the advantages of our network in the task of target detection in complex pathology images.

6.
Obesity (Silver Spring) ; 32(8): 1585-1593, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38956411

RESUMEN

OBJECTIVE: Observational studies have suggested associations of birth weight, childhood BMI, and adulthood BMI with thyroid function or diseases. However, the causal relationships remain unclear due to residual confounding inherent in conventional epidemiological studies. METHODS: We performed a two-sample Mendelian randomization (MR) study to investigate causal relationships of genetically predicted birth weight, childhood BMI, and adulthood BMI with a range of clinically relevant thyroid outcomes. Additionally, we conducted a reverse MR analysis on adulthood BMI. Data on exposures and outcomes were obtained from large-scale genome-wide association study meta-analyses predominantly composed of individuals of European ancestry. RESULTS: The MR analysis revealed no evidence of causal associations of birth weight or BMI at different life stages with thyrotropin (TSH) levels, hypothyroidism, hyperthyroidism, autoimmune thyroid disorders, or thyroid cancer. Contrarily, thyroid cancer demonstrated a significant causal relationship with increased adulthood BMI (ß = 0.010, 95% CI: 0.006-0.015; p = 5.21 × 10-6). CONCLUSIONS: Our comprehensive MR did not find causal links of birth weight, childhood BMI, or adulthood BMI with thyroid diseases but provided evidence that thyroid cancer may play a role in weight gain. Our research findings offer valuable insights into the intricate relationship between body weight and thyroid health throughout an individual's life.


Asunto(s)
Peso al Nacer , Índice de Masa Corporal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Enfermedades de la Tiroides , Humanos , Enfermedades de la Tiroides/genética , Enfermedades de la Tiroides/epidemiología , Femenino , Adulto , Masculino , Glándula Tiroides/fisiopatología , Niño , Tirotropina/sangre , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/epidemiología
7.
J Immunother Cancer ; 12(6)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38908858

RESUMEN

BACKGROUND: Previous studies have suggested the potential synergistic antitumor activity when combining immune checkpoint inhibitors with anti-angiogenic agents in various solid tumors. We aimed to assess the efficacy and safety of camrelizumab (a humanized programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) for patients with advanced mucosal melanoma (MM), and explore-related biomarkers. METHODS: We conducted a single-center, open-label, single-arm, phase II study. Patients with unresectable or recurrent/metastatic MM received camrelizumab and apatinib. The primary endpoint was the confirmed objective response rate (ORR). RESULTS: Between April 2019 and June 2022, 32 patients were enrolled, with 50.0% previously received systemic therapy. Among 28 patients with evaluable response, the confirmed ORR was 42.9%, the disease control rate was 82.1%, and the median progression-free survival (PFS) was 8.05 months. The confirmed ORR was 42.9% (6/14) in both treatment-naïve and previously treated patients. Notably, treatment-naïve patients had a median PFS of 11.89 months, and those with prior treatment had a median PFS of 6.47 months. Grade 3 treatment-related adverse events were transaminase elevation, rash, hyperbilirubinemia, proteinuria, hypertension, thrombocytopenia, hand-foot syndrome and diarrhea. No treatment-related deaths were observed. Higher tumor mutation burden (TMB), increased T-cell receptor (TCR) diversity, and altered receptor tyrosine kinase (RTK)/RAS pathway correlated with better tumor response. CONCLUSION: Camrelizumab plus apatinib provided promising antitumor activity with acceptable toxicity in patients with advanced MM. TMB, TCR diversity and RTK/RAS pathway genes were identified as potential predictive biomarkers and warrant further validation. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR1900023277.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Melanoma , Piridinas , Humanos , Masculino , Femenino , Melanoma/tratamiento farmacológico , Melanoma/patología , Piridinas/uso terapéutico , Piridinas/administración & dosificación , Piridinas/farmacología , Piridinas/efectos adversos , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anciano , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Membrana Mucosa/efectos de los fármacos , Membrana Mucosa/patología
8.
Sci Rep ; 14(1): 13733, 2024 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877212

RESUMEN

Although there is an association between abdominal aortic aneurysm (AAA) and circulating immune cell phenotypes, the exact causal relationship remains unclear. This study aimed to explore the causal relationships between immune cell phenotypes and AAA risk using a bidirectional two-sample Mendelian randomization approach. Data from genome-wide association studies pertaining to 731 immune cell traits and AAA were systematically analyzed. Using strict selection criteria, we identified 339 immune traits that are associated with at least 3 single nucleotide polymorphisms. A comprehensive MR analysis was conducted using several methods including Inverse Variance Weighted, Weighted Median Estimator, MR-Egger regression, Weighted Mode, and Simple Median methods. CD24 on switched memory cells (OR = 0.922, 95% CI 0.914-0.929, P = 2.62e-79) at the median fluorescence intensities level, and SSC-A on HLA-DR + natural killer cells (OR = 0.873, 95% CI 0.861-0.885, P = 8.96e-81) at the morphological parameter level, exhibited the strongest causal associations with AAA. In the reverse analysis, no significant causal effects of AAA on immune traits were found. The study elucidates the causal involvement of multiple circulating immune cell phenotypes in AAA development, signifying their potential as diagnostic markers or therapeutic targets. These identified immune traits may be crucial in modulating AAA-related inflammatory pathways.


Asunto(s)
Aneurisma de la Aorta Abdominal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Aneurisma de la Aorta Abdominal/genética , Aneurisma de la Aorta Abdominal/sangre , Aneurisma de la Aorta Abdominal/inmunología , Humanos , Predisposición Genética a la Enfermedad , Fenotipo , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Factores de Riesgo
9.
World J Surg Oncol ; 22(1): 150, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844951

RESUMEN

PURPOSE: To evaluate the predictors for short and long term urinary continence (UC) recovery after laparoscopic radical prostatectomy (LRP) from clinical and oncological variables. METHODS: We retrospectively collected data from 142 prostate cancer patients who underwent LRP between September 2014 and June 2021 at a tumor specialist diagnosis and treatment center in China. The rate of post-prostatectomy incontinence (PPI) was evaluated from immediate and at 3, 6 and 12 mo after LRP, and UC was defined as the use of no or one safety pad. Sixteen clinical and oncological variables were analyzed by univariate and multivariate regression analysis to determine whether they were associated with short (3 mo) or long term (12 mo) UC recovery after LRP. RESULTS: After eliminating patients who were lost to follow-up, 129 patients were eventually included. The mean ± SD age was 68 ± 6.3 years. The UC rates of immediate, 3, 6 and 12 mo after the operation were 27.9%, 54.3%, 75.2% and 88.4%, respectively. Multivariate analyses revealed that membranous urethral length (MUL) was a protective predictor of UC after catheter extraction(P < 0.001), and at 3 mo (P < 0.001), 6 mo (P < 0.001) and 12 mo (P = 0.009) after surgery. CONCLUSION: MUL is a significant independent factor that can contribute to short and long term UC recovery post-LRP, which may assist clinicians and their patients in counseling of treatment.


Asunto(s)
Laparoscopía , Complicaciones Posoperatorias , Prostatectomía , Neoplasias de la Próstata , Incontinencia Urinaria , Humanos , Masculino , Prostatectomía/efectos adversos , Prostatectomía/métodos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Neoplasias de la Próstata/cirugía , Incontinencia Urinaria/etiología , Incontinencia Urinaria/epidemiología , Anciano , Estudios Retrospectivos , China/epidemiología , Complicaciones Posoperatorias/etiología , Estudios de Seguimiento , Pronóstico , Persona de Mediana Edad , Recuperación de la Función
10.
ESC Heart Fail ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38867366

RESUMEN

AIMS: Type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular disease (CVD) risk, but whether T2DM directly causes adverse cardiac remodelling is uncertain. We performed a comprehensive Mendelian randomization (MR) analysis to investigate the causal relevance of T2DM to CVD outcomes and cardiac structure/function. METHODS AND RESULTS: Bidirectional two-sample MR was conducted using summary-level data from European-ancestry genome-wide association studies. The T2DM GWAS data included 80 154 cases and 853 816 controls from the DIAGRAM consortium. Outcomes included coronary artery disease (CAD), myocardial infarction (MI), stroke, heart failure, atrial fibrillation, and various quantitative cardiac imaging traits assessed by magnetic resonance imaging. MR analysis revealed causal associations between genetic predisposition to T2DM and increased risk of CAD (odds ratio [OR] 1.104, 95% confidence interval [CI] 1.078-1.130, P = 2.59e-16), MI (OR 1.129, 95% CI 1.094-1.166, P = 6.02e-14) and stroke (OR 1.086, 95% CI 1.064-1.109, P = 1.02e-14). These associations were validated in the FinnGen cohort (CAD: OR 1.117, 95% CI 1.075-1.158, P = 1.56e-9; MI: OR 1.132, 95% CI 1.083-1.184, P = 4.27e-8; stroke: OR 1.138, 95% CI 1.107-1.170, P = 3.52e-20). Multivariable MR show consistent findings (CAD: OR 1.063, 95% CI 1.031-1.097, P = 1.11e-4; MI: OR 1.088, 95% CI 1.042-1.135, P = 1.12e-4; stroke: OR 1.066, 95% CI 1.032-1.101, P = 1.18e-4) after adjusting for cardiometabolic traits. T2DM was causally associated with higher left ventricular mass index (ß = 0.473, 95% CI 0.193 to 0.752, P = 0.001), lower indexed right atrial minimum (ß = -0.048, 95% CI -0.073 to -0.022, P = 2.1e-5), and maximum (ß = -0.042, 95% CI -0.065 to -0.019, P = 4.12e-5) areas. The effects on right atrial size remained significant after adjusting for risk factors (minimum area: ß = -0.041, 95% CI -0.072 to -0.010, P = 0.009; maximum area: ß = -0.039, 95% CI -0.069 to -0.008, P = 0.012). Both apolipoprotein A1 and SBP are important mediators in the causal relationship between T2DM and left ventricular mass index. No reverse causal associations were identified. CONCLUSIONS: Our MR study demonstrates that genetic liability to T2DM plays causal roles in CAD, MI, stroke, and cardiac structure changes including left ventricular hypertrophy and reduced right atrial dimensions. These findings provide genetic evidence supporting glycaemic control in T2DM to mitigate cardiovascular complications and adverse cardiac remodelling.

11.
Heart Lung ; 67: 70-79, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38714139

RESUMEN

BACKGROUND: Inflammation is implicated in cardiovascular disease (CVD) pathogenesis, but causal roles of specific circulating inflammatory cytokines remain unclear. Mendelian randomization (MR) studies are well-poised to provide etiological insights beyond constraints of conventional research. METHODS: We conducted a large-scale MR study to investigate potential causal relationships of 91 inflammatory proteins with CVD outcomes and cardiac remodeling using summary-level genetic data. Outcomes included coronary artery disease, myocardial infarction, stroke, atrial fibrillation, heart failure, abdominal aortic aneurysm, deep vein thrombosis of lower extremities, pulmonary embolism, cardiac structure and functional parameters. Inverse-variance weighted analysis was undertaken as the primary analysis, with several sensitivity analyses applied. RESULTS: Hepatocyte growth factor (HGF) demonstrated a causal relationship with increased susceptibility to both any stroke (OR 1.111; 95 % CI 1.044 - 1.183; P = 9.50e-04) and ischemic stroke (OR 1.121; 95 % CI 1.047 - 1.200; P = 1.04e-03). Programmed cell death 1 ligand 1 (PD-L1) was negatively associated with atrial fibrillation risk (OR 0.936, 95 % CI 0.901 - 0.973; P = 7.69e-04). CCL20, CDCP1, Flt3L and IL-10RA were identified as causal coronary artery disease risk factors, while LIF and ST1A1 had protective effects. IL-4 and LIF-R demonstrated causal links with right heart functional changes. CONCLUSIONS: Our MR study nominates specific circulating inflammatory cytokines as potential targets for CVD treatment and prevention. Further research into mechanisms and clinical translation are warranted.


Asunto(s)
Citocinas , Análisis de la Aleatorización Mendeliana , Humanos , Citocinas/sangre , Citocinas/metabolismo , Análisis de la Aleatorización Mendeliana/métodos , Cardiopatías/sangre , Cardiopatías/etiología , Cardiopatías/fisiopatología , Inflamación/sangre , Masculino , Femenino
12.
Heart Rhythm ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38750912

RESUMEN

BACKGROUND: Thyroid hormones play a crucial role in cardiovascular physiology. Subclinical thyroid dysfunction has been associated with adverse cardiovascular outcomes, but evidence is mixed regarding causality. OBJECTIVE: The purpose of this study was to investigate the potential causal relationships of thyroid-stimulating hormone (TSH), free thyroxine, hypothyroidism, and hyperthyroidism with cardiovascular outcomes, including atrial fibrillation (AF), coronary artery disease, myocardial infarction, heart failure, and ischemic stroke, as well as their effect on cardiac structure and function assessed by cardiac magnetic resonance imaging. METHODS: A comprehensive 2-sample Mendelian randomization analysis was performed using summary data from large-scale meta-analyses of European ancestry individuals. RESULTS: Genetically determined lower TSH levels (odds ratio 0.928; 95% confidence interval 0.884-0.974; P = .003) and genetic risk of hyperthyroidism (odds ratio 1.049; 95% confidence interval 1.016-1.083; P = .003) were associated with increased AF risk. These associations remained significant even after adjusting for cardiovascular risk factors. Colocalization and multivariable Mendelian randomization revealed height as a key mediator between TSH/hyperthyroidism and AF. These findings were further corroborated in the independent FinnGen cohort. However, no clear evidence was found for relationships between thyroid function and other cardiovascular outcomes and cardiac structure and function. CONCLUSION: Our study shows that reduced TSH levels and hyperthyroidism heighten AF risk, with height serving as an important mediator in these associations. The primary focus of thyroid management in cardiovascular health should be on preventing and treating arrhythmias, particularly AF. Our research highlights the importance of routine screening and timely treatment of thyroid dysfunction to optimize the prevention and management of arrhythmias.

13.
J Neural Eng ; 21(3)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38812288

RESUMEN

Objective. Magnetoencephalography (MEG) shares a comparable time resolution with electroencephalography. However, MEG excels in spatial resolution, enabling it to capture even the subtlest and weakest brain signals for brain-computer interfaces (BCIs). Leveraging MEG's capabilities, specifically with optically pumped magnetometers (OPM-MEG), proves to be a promising avenue for advancing MEG-BCIs, owing to its exceptional sensitivity and portability. This study harnesses the power of high-frequency steady-state visual evoked fields (SSVEFs) to build an MEG-BCI system that is flickering-imperceptible, user-friendly, and highly accurate.Approach.We have constructed a nine-command BCI that operates on high-frequency SSVEF (58-62 Hz with a 0.5 Hz interval) stimulation. We achieved this by placing the light source inside and outside the magnetic shielding room, ensuring compliance with non-magnetic and visual stimulus presentation requirements. Five participants took part in offline experiments, during which we collected six-channel multi-dimensional MEG signals along both the vertical (Z-axis) and tangential (Y-axis) components. Our approach leveraged the ensemble task-related component analysis algorithm for SSVEF identification and system performance evaluation.Main Results.The offline average accuracy of our proposed system reached an impressive 92.98% when considering multi-dimensional conjoint analysis using data from both theZandYaxes. Our method achieved a theoretical average information transfer rate (ITR) of 58.36 bits min-1with a data length of 0.7 s, and the highest individual ITR reached an impressive 63.75 bits min-1.Significance.This study marks the first exploration of high-frequency SSVEF-BCI based on OPM-MEG. These results underscore the potential and feasibility of MEG in detecting subtle brain signals, offering both theoretical insights and practical value in advancing the development and application of MEG in BCI systems.


Asunto(s)
Interfaces Cerebro-Computador , Potenciales Evocados Visuales , Magnetoencefalografía , Estimulación Luminosa , Humanos , Magnetoencefalografía/métodos , Potenciales Evocados Visuales/fisiología , Adulto , Masculino , Femenino , Estimulación Luminosa/métodos , Adulto Joven , Corteza Visual/fisiología
14.
Clin Immunol ; 263: 110219, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38631594

RESUMEN

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two common subtypes of autoimmune bullous disease (AIBD). The key role of circulating autoreactive immune cells contributing to skin damage of AIBD has been widely recognized. Nevertheless, the immune characteristics in cutaneous lesions remain unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell VDJ sequencing (scRNA-seq) to generate transcriptional profiles for cells and T/B cell clonetype in skin lesions of BP and PV. We found that the proportions of NK&T, macrophages/ dendritic cells, B cells, and mast cells increased in BP and PV lesions. Then, BP and PV cells constituted over 75% of all myeloid cell subtypes, CD4+ T cell subtypes and CD8+ T cell subtypes. Strikingly, CD8+ Trm was identified to be expanded in PV, and located in the intermediate state of the pseudotime trajectory from CD8+ Tm to CD8+ Tem. Interestingly, CD8+ Tem and CD4+ Treg highly expressed exhaustion-related genes, especially in BP lesions. Moreover, the enhanced cell communication between stromal cells and immune cells like B cells and macrophages/ dendritic cells was also identified in BP and PV lesions. Finally, clone expansion was observed in T cells of BP and PV compared with HC, while CD8+ Trm represented the highest ratio of hyperexpanded TCR clones among all T cell subtypes. Our study generally depicts a large and comprehensive single-cell landscape of cutaneous lesions and highlights immune cell features in BP and PV. This offers potential research targets for further investigation.


Asunto(s)
Penfigoide Ampolloso , Pénfigo , Análisis de la Célula Individual , Humanos , Penfigoide Ampolloso/inmunología , Penfigoide Ampolloso/genética , Penfigoide Ampolloso/patología , Pénfigo/inmunología , Pénfigo/genética , Pénfigo/patología , Análisis de la Célula Individual/métodos , Piel/inmunología , Piel/patología , Linfocitos T CD8-positivos/inmunología , Femenino , Masculino , Análisis de Secuencia de ARN , Linfocitos T CD4-Positivos/inmunología , Macrófagos/inmunología , Linfocitos B/inmunología , Anciano , Células Dendríticas/inmunología , Persona de Mediana Edad
15.
Exp Dermatol ; 33(4): e15082, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38664884

RESUMEN

As a chronic relapsing disease, psoriasis is characterized by widespread skin lesions. The Psoriasis Area and Severity Index (PASI) is the most frequently utilized tool for evaluating the severity of psoriasis in clinical practice. Nevertheless, long-term monitoring and precise evaluation pose difficulties for dermatologists and patients, which is time-consuming, subjective and prone to evaluation bias. To develop a deep learning system with high accuracy and speed to assist PASI evaluation, we collected 2657 high-quality images from 1486 psoriasis patients, and images were segmented and annotated. Then, we utilized the YOLO-v4 algorithm to establish the model via four modules, we also conducted a human-computer comparison through quadratic weighted Kappa (QWK) coefficients and intra-class correlation coefficients (ICC). The YOLO-v4 algorithm was selected for model training and optimization compared with the YOLOv3, RetinaNet, EfficientDet and Faster_rcnn. The model evaluation results of mean average precision (mAP) for various lesion features were as follows: erythema, mAP = 0.903; scale, mAP = 0.908; and induration, mAP = 0.882. In addition, the results of human-computer comparison also showed a median consistency for the skin lesion severity and an excellent consistency for the area and PASI score. Finally, an intelligent PASI app was established for remote disease assessment and course management, with a pleasurable agreement with dermatologists. Taken together, we proposed an intelligent PASI app based on the image YOLO-v4 algorithm that can assist dermatologists in long-term and objective PASI scoring, shedding light on similar clinical assessments that can be assisted by computers in a time-saving and objective manner.


Asunto(s)
Algoritmos , Aprendizaje Profundo , Psoriasis , Índice de Severidad de la Enfermedad , Psoriasis/patología , Humanos , Procesamiento de Imagen Asistido por Computador/métodos
16.
Cancer Immunol Immunother ; 73(6): 103, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38630135

RESUMEN

As one of the scheduled immunization vaccines worldwide, virtually all individuals have been vaccinated with BCG vaccine. In order to verify the hypothesis that delivering BCG high-affinity peptides to tumor areas could activate the existing BCG memory T cells to attack tumor, we firstly predicted the HLA-A*0201 high-affinity peptides of BCG Ag85A protein (KLIANNTRV, GLPVEYLQV), and then, A375 melanoma cells and HLA-A*0201 PBMCs (from PPD-positive adults) were added to co-incubated with the predicted peptides in vitro. We found that the predicted BCG high-affinity peptides could be directly loaded onto the surface of tumor cells, enhancing the tumor-killing efficacy of PBMCs from PPD-positive volunteer. Then, we constructed PPD-positive mice model bearing B16F10 subcutaneous tumors and found that intratumor injection of BCG Ag85A high-affinity peptides (SGGANSPAL, YHPQQFVYAGAMSGLLD) enhanced the anti-tumor efficacy in PPD-positive melanoma mice. Along with the better anti-tumor efficacy, the expression of PDL1 on tumor cell surface was also increased, and stronger antitumor effects occurred when further combined with anti-PD1 antibody. For microenvironment analysis, the proportion of effector memory T cells was increased and the better treatment efficacy may be attributed to the elevated effector memory CD4 + T cells within the tumor. In conclusion, using the existing immune response of BCG vaccine by delivering high-affinity peptides of BCG to tumor area is a safe and promising therapy for cancer.


Asunto(s)
Melanoma , Humanos , Adulto , Animales , Ratones , Melanoma/tratamiento farmacológico , Vacuna BCG/uso terapéutico , Péptidos , Modelos Animales de Enfermedad , Inmunización , Microambiente Tumoral
17.
Open Life Sci ; 19(1): 20220818, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38465333

RESUMEN

Stroke is a debilitating condition that often leads to disability and death. The increasing prevalence of stroke has drawn worldwide attention. Extensive evidence indicates a crucial role of genetic determinants in the occurrence and perpetuation of stroke. An Icelandic study identified a significant correlation of the phosphodiesterase 4D (PDE4D) single-nucleotide polymorphism (SNP) rs2910829 with stroke susceptibility. However, subsequent studies reported in Chinese populations were contradictory. We implemented a meta-analysis to inspect whether SNP rs2910829 is related to stroke susceptibility in Chinese populations and subsequently performed an in silico analysis to predict its potential functions. Finally, we analysed data from 24 studies comprising 7,484 Chinese stroke patients and 7,962 control individuals. Compared with the CC genotype, the TT genotype was associated with increased susceptibility to stroke (pooled odds ratio [OR] 1.28, 95% confidence interval [CI] 1.13-1.46, P < 0.001), whereas the CT genotype was not. Correspondingly, a significant association was detected under the recessive model (TT vs CT + CC: OR 1.30, 95% CI 1.15-1.47, P < 0.001). Similar results were obtained in large artery atherosclerosis (LAA) stroke but not in small vessel stroke. Bioinformatics analysis also revealed that SNP rs2910829 and its linked SNPs might be implicated in transcriptional regulation. This meta-analysis reveals significant relationships between the PDE4D SNP rs2910829 and susceptibility to stroke and subtype-LAA stroke in Chinese individuals, and further investigations are warranted to evaluate this effect.

18.
Cancer Med ; 13(7): e7137, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38545846

RESUMEN

INTRODUCTION: Acral melanoma (AM) is the most common subtype of malignant melanoma in China, with a very poor prognosis. Despite the frequent reporting of trauma events in AM cases, the precise etiology of AM remains elusive. METHODS: A retrospective analysis was conducted on a cohort of 303 AM patients at Nanjing Drum Tower Hospital. The patients were categorized into four distinct groups based on different patterns of disease onset: trauma type (Type 1), pigmented nevus type (Type 2), pigmented nevi with trauma (Type 3), and pigmented nevi with natural ulceration (Type 4). Differences in clinicopathological features, genetic alterations, and tumor immune microenvironment (TIME) were analyzed. RESULTS: Traumatic events accounted for a large proportion of AM cases. Among these categories, Type 1 patients displayed the least favorable pathological traits and an immunosuppressive TIME. Common copy number variations (CNVs) were observed in CCND1, RB1, FGF19, and IL7R, while CNVs in CDK4 and TERT occurred less frequently in patients with a history of trauma (Type 1 and Type 3). Type 2 patients exhibited the most favorable pathological characteristics and genetic profiles, and demonstrated the lowest incidence of CCDN1 and RB1 CNVs but had the highest CDK4 CNVs. In contrast, the pathological behavior of Type 3 and Type 4 patients was in between Type 1 and Type 2. And patients in Type 3 and Type 4 displayed a more favorable overall microenvironment. CONCLUSION: This study provides a clinical classification of Chinese AM based on diverse clinical onset characteristics and highlights the important role of trauma in AM. These findings may help to guide the diagnosis, treatment, and prognosis of AM patients. Further investigations are imperative to elucidate the underlying mechanisms governing the association between trauma and AM.


Asunto(s)
Melanoma , Nevo Pigmentado , Neoplasias Cutáneas , Humanos , Melanoma/patología , Estudios Retrospectivos , Variaciones en el Número de Copia de ADN , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Nevo Pigmentado/patología , Microambiente Tumoral/genética
19.
Medicine (Baltimore) ; 103(11): e37544, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38489698

RESUMEN

Secondary epilepsy is a common concomitant disease of viral encephalitis (VE) in children. However, the risk factors for secondary epilepsy after VE remain debated. The aim of this study was to perform a 10-year single-center retrospective analysis to investigate the incidence and risk factors of secondary epilepsy after VE in children. A total of 8691 patients suffered from VE in our hospital between December 2011 and February 2022 were included. The patients were divided into control group (Group C) and epilepsy group (Group E) according to whether they followed secondary epilepsy. Information about treatment process was collected from medical records to determine the incidence. Univariate analysis and multivariate logistic regression analysis were performed to identify the independent risk factors. In the current study, the occurrence of secondary epilepsy after VE in pediatric patients was 10.99% (385 of 3503). The results of univariate and multivariate analysis showed that unconsciousness, convulsions, times of epilepsy >2, epileptiform discharge of Electroencephalogram (EEG), and cortical and subcortical damage of magnetic resonance imaging/computer tomography were the significant risk factors for secondary epilepsy after VE. Nearly one tenth of pediatric patients suffered from secondary epilepsy after VE. Interventions for identified risk factors should be used to prevent the occurrence of secondary epilepsy.


Asunto(s)
Encefalitis Viral , Epilepsia , Humanos , Niño , Estudios Retrospectivos , Incidencia , Epilepsia/etiología , Epilepsia/complicaciones , Factores de Riesgo , Encefalitis Viral/complicaciones , Encefalitis Viral/epidemiología , Electroencefalografía/métodos
20.
Acta Biochim Biophys Sin (Shanghai) ; 56(3): 345-355, 2024 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-38419497

RESUMEN

Psoriasis is accepted as a chronic, inflammatory, immune-mediated skin disease triggered by complex environmental and genetic factors. For a long time, disease recurrence, drug rejection, and high treatment costs have remained enormous challenges and burdens to patients and clinicians. Natural products with effective immunomodulatory and anti-inflammatory activities from medicinal plants have the potential to combat psoriasis and complications. Herein, an imiquimod (IMQ)-induced psoriasis-like dermatitis model is established in mice. The model mice are treated with 1% rutaecarpine (RUT) (external use) or the oral administration of RUT at different concentrations. Furthermore, high-throughput 16S rRNA gene sequencing is applied to analyze the changes in the diversity and composition of the gut microbiota. Based on the observation of mouse dorsal skin changes, RUT can protect against inflammation to improve psoriasis-like skin damage in mice. Additionally, RUT could suppress the expression levels of proinflammatory cytokines (IL-23, IL-17A, IL-22, IL-6, and IFN-α) within skin tissue samples. Concerning gut microbiota, we find obvious variations within the composition of gut microflora between IMQ-induced psoriasis mice and RUT-treated psoriasis mice. RUT effectively mediates the recovery of gut microbiota in mice induced by IMQ application. Psoriasis is linked to the production of several inflammatory cytokines and gut microbiome alterations. This research shows that RUT might restore gut microbiota homeostasis, reduce inflammatory cytokine production, and ameliorate psoriasis symptoms. In conclusion, the gut microbiota might be a therapeutic target or biomarker for psoriasis that aids in clinical diagnosis and therapy.


Asunto(s)
Dermatitis , Microbioma Gastrointestinal , Alcaloides Indólicos , Psoriasis , Quinazolinonas , Humanos , Animales , Ratones , Imiquimod/efectos adversos , ARN Ribosómico 16S/genética , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológico , Citocinas/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos BALB C
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