RESUMEN
Acute myeloid leukemia (AML) is one of the most common types of blood cancer in adults and is associated with a poor survival rate. NK cells play a crucial role in combating AML, and alterations in immune checkpoint expression can impair NK cell function against AML. Targeting certain checkpoints may restore this function. CD96, an inhibitory immune checkpoint, has unclear expression and roles on NK cells in AML patients. In this study, we initially evaluated CD96 expression and compared CD96+ NK with the inhibitory receptor and stimulatory receptors on NK cells from AML patients at initial diagnosis. We observed increased CD96 expression on NK cells with dysfunctional phenotype. Further analysis revealed that CD96+ NK cells had lower IFN-γ production than CD96- NK cells. Blocking CD96 enhanced the cytotoxicity of primary NK and cord blood-derived NK (CB-NK) cells against leukemia cells. Notably, patients with a high frequency of CD96+ NK cells at initial diagnosis exhibited poorer clinical outcomes. Additionally, TGF-ß1 was found to enhance CD96 expression on NK cells via SMAD3 signaling. These findings suggest that CD96 is invovled in NK dysfunction against AML blast, and might be a potential target for restoring NK cell function in the fight against AML.
RESUMEN
PURPOSE: Idiopathic pulmonary fibrosis (IPF), a chronic and progressively worsening condition characterized by interstitial lung inflammation and fibrosis of unknown etiology, has a grim prognosis. The treatment options for IPF are limited and new therapeutic strategies are urgently needed. Dietary restriction can improve various inflammatory diseases, but its therapeutic effect on bleomycin (BLM)-induced pulmonary fibrosis mouse model remains unclear. This study aims to investigate whether intermittent fasting (IF) can alleviate BLM-induced pulmonary inflammation and fibrosis. METHODS: Pulmonary fibrosis mouse models were induced by BLM. The IF group underwent 24-h fasting cycles for one week prior and three weeks following BLM administration. Meanwhile, the ad libitum feeding group had unrestricted access to food throughout the experiment. The evaluation focused on lung pathology via histological staining, qPCR analysis of collagen markers, and immune cell profiling through flow cytometry. RESULTS: IF group significantly reduced inflammation and fibrosis in lung tissues of BLM-induced mice compared to ad libitum feeding group. qPCR results showed IF remarkably decreased the mRNA expression of Col 1a and Col 3a in the lungs of BLM-induced mouse models. IF also reduced the numbers of regulatory T cells (Tregs), T helper 17 (Th17) cells, monocytes, and monocyte-derived alveolar macrophages (MoAMs) in the lung tissues. CONCLUSIONS: IF may improve BLM-induced pulmonary fibrosis by decreasing numbers of immune cells including Treg cells, Th17 âcells, monocytes, and MoAMs in the lungs. This study offers experimental validation for dietary intervention as a viable treatment modality in IPF management.
RESUMEN
Nanozymes, nanostructured materials emulating natural enzyme activities, exhibit potential in catalyzing reactive oxygen species (ROS) production for cancer treatment. By facilitating oxidative reactions, elevating ROS levels, and influencing the tumor microenvironment (TME), nanozymes foster the eradication of cancer cells. Noteworthy are their superior stability, ease of preservation, and cost-effectiveness compared to natural enzymes, rendering them invaluable for medical applications. This comprehensive review intricately explores the interplay between ROS and tumor therapy, with a focused examination of metal-based nanozyme strategies mitigating tumor hypoxia. It provides nuanced insights into diverse catalytic processes, mechanisms, and surface modifications of various metal nanozymes, shedding light on their role in intra-tumoral ROS generation and applications in antioxidant therapy. The review concludes by delineating specific potential prospects and challenges associated with the burgeoning use of metal nanozymes in future tumor therapies.
Asunto(s)
Neoplasias , Especies Reactivas de Oxígeno , Microambiente Tumoral , Humanos , Especies Reactivas de Oxígeno/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Animales , Microambiente Tumoral/efectos de los fármacos , Nanoestructuras/química , Antioxidantes/farmacología , Antioxidantes/química , Antineoplásicos/farmacología , Antineoplásicos/química , Metales/química , Hipoxia Tumoral/efectos de los fármacosRESUMEN
Quantum heat engines and refrigerators are open quantum systems, whose dynamics can be well understood using a non-Hermitian formalism. A prominent feature of non-Hermiticity is the existence of exceptional points (EPs), which has no counterpart in closed quantum systems. It has been shown in classical systems that dynamical encirclement in the vicinity of an EP, whether the loop includes the EP or not, could lead to chiral mode conversion. Here, we show that this is valid also for quantum systems when dynamical encircling is performed in the vicinity of their Liouvillian EPs (LEPs), which include the effects of quantum jumps and associated noise-an important quantum feature not present in previous works. We demonstrate, using a Paul-trapped ultracold ion, the first chiral quantum heating and refrigeration by dynamically encircling a closed loop in the vicinity of an LEP. We witness the cycling direction to be associated with the chirality and heat release (absorption) of the quantum heat engine (quantum refrigerator). Our experiments have revealed that not only the adiabaticity breakdown but also the Landau-Zener-Stückelberg process play an essential role during dynamic encircling, resulting in chiral thermodynamic cycles. Our observations contribute to further understanding of chiral and topological features in non-Hermitian systems and pave a way to exploring the relation between chirality and quantum thermodynamics.
RESUMEN
Objective: Psoriasis is a common chronic inflammatory disease. However, trace elements are essential to biochemical processes of the skin, it is suspected that the trace elements are vital in the pathogenesis of psoriasis. Our research is aimed to investigate the association between serum levels and dietary intake levels of selenium, zinc, and copper with psoriasis. Methods: In this cross-sectional study, we utilized the National Health and Nutrition Examination Survey data from 2011 to 2014 to examine the association between psoriasis and serum concentration and dietary intake of trace elements including copper, zinc, and selenium in the US individuals. Our research combined two cycles and weighted the data. Student's t-tests and χ2 test were used. Subgroup analyses and interaction tests were conducted by IBM SPSS Statistics 22 and EmpowerStats. Results: This study indicates that the population with psoriasis has a lower dose of dietary intake selenium than the controls, and risk analysis showed that the men with selenium daily intake >150 mcg/day have a decreasing risk for psoriasis compared to those with daily intaking selenium <75 mcg/day. However, there are no differences on daily intake of selenium, zinc, and copper and serum levels of Zinc and Copper between psoriasis and healthy controls. The current study showed that the psoriasis group was significantly older with a bigger waist circumference, a higher education level, a higher ratio of people with smoke every day, and a higher ratio of people in USA and being non-Hispanic White. Conclusion: This cross-section study showed that a high selenium intake may benefit USA adults from psoriasis, especially for males. The social and cultural background and ethnic differences between the two groups influence the eating and living models, including the trace element intake. The national recommended dietary allowances (RDAs) might be considered to be modified with more reliable investigative clinical data and certain considering the social and cultural models.
RESUMEN
Importance: Due to comorbidities and associated safety risks, the management of severe atopic dermatitis (AD) in pediatric and adolescent patients poses significant challenges. Objective: To examine the efficacy and safety of systemic therapies for the treatment of moderate-to-severe atopic dermatitis in children and adolescents. Evidence review: On Feb 29, 2024, a systematic literature search was conducted in Embase, PubMed, and the Cochrane Central Register of Controlled Trials (Central). No date restrictions were applied. Randomized clinical trials, cohort studies, large case series, and meta-analyses were assessed to evaluate the efficacy (or effectiveness) and/or safety of systemic treatments for moderate-to-severe atopic dermatitis in children and adolescents. Findings: A preliminary search yielded 1457 results, from which 19 unique articles with a total of 3741 patients were included in the analysis. Overall, the available data for each systemic medication are limited, and the overall quality of the included studies on conventional systemic treatments is relatively low. When Dupilumab was used as a standalone treatment, 30%-40% of infants and toddlers aged 6 months to 2 years achieved EASI-75, while 50% of patients aged 2 to 6 years achieved EASI-75. In children aged 6 to 12 years, 33.0%-59.0% of atopic dermatitis patients achieved EASI-75, and when combined with topical corticosteroids (TCS), 69.7%-74.6% achieved EASI-75. Long-term data showed EASI-75 rates ranging from 75.0% to 94.0% for this age group. For adolescents aged 12 to 18 years, 40%-71% of patients achieved EASI-75 within 12 to 16 weeks, and by week 52, 80.8% of patients achieved EASI-75.Abrocitinib treatment resulted in 68.5%-72.0% of patients achieving EASI-75. Omalizumab treatment at week 24 showed a percentage change in SCORAD scores of -12.4%. In the Methotrexate treatment group, there was a SCORAD change of -26.25% at week 12, while the Cyclosporine A group had a SCORAD change of -25.01%. Patients treated with IVIG (Intravenous Immunoglobulin) showed a -34.4% change in SCORAD percentage scores at week 4, which further decreased by 47.12% at week 24. Patients receiving 4mg of Baricitinib and TCS had a 52.5% rate of EASI-75 at 16 weeks, and patients receiving different doses of upadacitinib had a 63-75% rate of EASI-75 at 16 weeks. The rate of EASI-75 at 16 weeks was around 28% in patients who received various doses of Tralokinumab.The most common adverse events observed were nasopharyngitis, respiratory events and dermatitis atopic. Conclusions and relevance: Awareness of adverse events and concomitant medications is crucial, and appropriate dosing and frequent laboratory and clinical monitoring are also essential. More real-world evidence and prospective cohort studies analyzing the effectiveness and safety of systemic therapies in children and adolescents are of paramount importance for optimizing personalized, effective, and safe management of the growing population of patients with atopic dermatitis in this age group.
Asunto(s)
Dermatitis Atópica , Humanos , Dermatitis Atópica/tratamiento farmacológico , Niño , Adolescente , Preescolar , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Lactante , Femenino , Masculino , Fármacos Dermatológicos/uso terapéutico , Fármacos Dermatológicos/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversosRESUMEN
Psoriasis is a chronic immune mediated inflammatory skin disease with systemic manifestations. It has been reported that caloric restriction could improve severity of psoriasis patients. However, the mechanism of intermittent fasting effects on psoriasis has not been investigated. Caloric restriction is known to reduce the number of circulating inflammatory monocytes in a CCL2-dependent manner. However, it is still unknown whether caloric restriction can improve psoriasis by regulating monocytes through CCL2. In this study, we used imiquimod (IMQ)-induced psoriasis-like mouse model to explore the effects and the mechanisms of intermittent fasting on psoriasis-like dermatitis. We found that intermittent fasting could significantly improve IMQ-induced psoriasis-like dermatitis, and reduce the number of γδT17 cells and IL-17 production in draining lymph nodes and psoriatic lesion via inhibiting proliferation and increasing death of γδT17 cells. Furthermore, intermittent fasting could significantly decrease monocytes in blood, and this was associated with decreased monocytes, macrophages and DC in psoriasis-like skin inflammation. Reduced monocytes in circulation and increased monocytes in BM of fasting IMQ-induced psoriasis-like mice is through reducing the production of CCL2 from BM to inhibit monocyte egress to the periphery. Our above data shads light on the mechanisms of intermittent fasting on psoriasis.
Asunto(s)
Quimiocina CCL2 , Modelos Animales de Enfermedad , Ayuno , Imiquimod , Monocitos , Psoriasis , Animales , Psoriasis/inmunología , Psoriasis/inducido químicamente , Psoriasis/patología , Monocitos/inmunología , Monocitos/metabolismo , Ratones , Ayuno/sangre , Quimiocina CCL2/metabolismo , Células Th17/inmunología , Interleucina-17/metabolismo , Piel/patología , Piel/inmunología , Humanos , Ratones Endogámicos C57BL , Masculino , Proliferación Celular , Restricción Calórica , Ayuno IntermitenteRESUMEN
BACKGROUND: We recently encountered a Rhnull phenotype proband within one family in the Chinese population. Rhnull is a rare autosomal recessive disorder characterized by the absence of the Rh antigens on the erythrocyte membrane, resulting in chronic hemolytic anemia. This study described the serological and molecular analysis of a Chinese Rhnull proband and his immediate family. METHODS: Red blood cells antigen phenotyping and antibody screening/identification were conducted. RHD, RHCE, and RHAG were analyzed using genomic DNA by polymerase chain reaction and sequence analysis. RESULTS: Serologic tests showed a D-C-E-c-e- phenotype in the proband associated with the suspicion of anti-Rh29 (titer 16). Molecular analyses showed a new mutation (c.406dupA) in exon 3 of RHAG. This duplication introduced a reading frameshift (p.Thr136AsnfsTer21). The RHAG mutation was found in the homozygous state for the proband and heterozygous state for his parents. CONCLUSION: We identified a novel RHAG mutation resulting in the Rhnull phenotype of the regulator type. Inheritance of the novel allele was shown by family study.
Asunto(s)
Mutación del Sistema de Lectura , Fenotipo , Sistema del Grupo Sanguíneo Rh-Hr , Femenino , Humanos , Masculino , Proteínas Sanguíneas , Pueblos del Este de Asia , Glicoproteínas de Membrana/genética , Linaje , Sistema del Grupo Sanguíneo Rh-Hr/genéticaRESUMEN
Outbreaks of viral diseases seriously jeopardize people's health and cause huge economic losses. At the same time, virology provides a new perspective for biology, molecular biology and cancer research, and it is important to study the discovered viruses with potential applications. Therefore, the development of immediate and rapid viral detection methods for the prevention and treatment of viral diseases as well as the study of viruses has attracted extensive attention from scientists. With the continuous progress of science and technology, especially in the field of bioanalysis, a series of new detection techniques have been applied to the on-site rapid detection of viruses, which has become a powerful approach for human beings to fight against viruses. In this paper, the latest research progress of rapid point-of-care detection of viral nucleic acids, antigens and antibodies is presented. In addition, the advantages and disadvantages of these technologies are discussed from the perspective of practical application requirements. Finally, the problems and challenges faced by rapid viral detection methods and their development prospects are discussed.
Asunto(s)
Pruebas en el Punto de Atención , Virus , Humanos , Virus/aislamiento & purificación , Virus/genética , Virosis/diagnóstico , Antígenos Virales/análisis , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/análisis , Técnicas Biosensibles/métodos , Sistemas de Atención de Punto , ARN Viral/análisis , ARN Viral/genéticaRESUMEN
BACKGROUND: There was evidence that significant bidirectional associations between psoriasis and inflammatory bowel diseases (IBDs), which influences management strategy of the patients, so the investigation on the mechanisms by which these two diseases co-occur is important. METHODS: The Gene Expression Omnibus (GEO) database was used to download gene expression profiles of psoriasis and IBD. The differentially expressed genes (DEGs) between disease and health control groups for each data set were calculated, and Venn diagram was used to obtain for intersection. We performed Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on the intersection, followed by developing a protein-protein interaction network and module construction, and identified hub genes by cytoHubba. Thereafter, least absolute shrinkage and selection operator algorithms was used to identify the co-biomarkers of psoriasis and IBD from the top 50 hub genes. The biomarkers were used to construct a screening model, the discriminatory capacity of which was verified by receiver operating characteristic (ROC) curves. CIBERSORT algorithm was utilized to estimate the compositional patterns of immune cell infiltration in biomarkers of psoriasis and IBD. Spearman rank correlation analysis was used to further evaluate the correlation between the identified biomarkers and immune cells. RESULTS: A total of 271 shared DEGs were screened. The GO and KEGG enrichment analysis indicated that the shared DEGs were mainly enriched in response to lipopolysaccharide, secretory granule lumen, cytokine activity, and interleukin (IL)-17 signaling pathway. Fifty genes such as IL1B, IL6, were identified as hub genes, based on which, FOS, IFI44, MMP9, MNDA, PTGS2, S100A9, and STAT1 were identified as biomarkers of psoriasis. CCL20, CD274, CTGF, CXCL1, CXCL10, CXCL2, CXCL9, FCGR3B, FOS, GBP1, GZMB, IFI27, IFI6, IL1RN, ISG15, ISG20, LCN2, LILRB2, MMP12, MMP7, S100A8, TLR8, and TNFSF13B were identified as biomarkers of IBD. FOS was the common biomarker of psoriasis and IBD. Screening models were validated in the validation data set (Psoriasis: area under the curve (AUC) = 1.000, IBD: AUC = 0.870). Immunocyte infiltration analysis showed the macrophages cells, mast cells resting, and T cells CD4 memory activated have the common characteristics in psoriasis and IBD. CONCLUSIONS: FOS may play a key role in the occurrence and development of psoriasis complicated with IBD and macrophages cells may be an entrance for treating this comorbidity.
Asunto(s)
Enfermedades Inflamatorias del Intestino , Psoriasis , Humanos , Comorbilidad , Enfermedades Inflamatorias del Intestino/epidemiología , Psoriasis/epidemiología , Algoritmos , BiomarcadoresRESUMEN
The discovery and utilization of natural products derived from endophytic microorganisms have garnered significant attention in pharmaceutical research. While remarkable progress has been made in this field each year, the absence of dedicated open-access databases for endophytic microorganism natural products research is evident. To address the increasing demand for mining and sharing of data resources related to endophytic microorganism natural products, this study introduces EMNPD, a comprehensive endophytic microorganism natural products database comprising manually curated data. Currently, EMNPD offers 6632 natural products from 1017 endophytic microorganisms, targeting 1286 entities (including 94 proteins, 282 cell lines, and 910 species) with 91 diverse bioactivities. It encompasses the physico-chemical properties of natural products, ADMET information, quantitative activity data with their potency, natural products contents with diverse fermentation conditions, systematic taxonomy, and links to various well-established databases. EMNPD aims to function as an open-access knowledge repository for the study of endophytic microorganisms and their natural products, thereby facilitating drug discovery research and exploration of bioactive substances. The database can be accessed at http://emnpd.idrblab.cn/ without the need for registration, enabling researchers to freely download the data. EMNPD is expected to become a valuable resource in the field of endophytic microorganism natural products and contribute to future drug development endeavors.
RESUMEN
Isotretinoin (ISO) is a powerful vitamin A derivative that offers the potential for treatment of permanent remission of acne; however, its potential side effects on both physiological and psychological aspects limit its application. This article reviews the side effects of ISO from physiological and psychological aspects in detail, to better screen the suitable population of ISO and improve the efficiency of clinical treatment. Our findings indicate that ISO may cause teratogenicity, skin reactions, ocular reactions, changes in blood indicators, and occasional acne fulminans. To optimize clinical treatment, more attention should be paid to identifying the specific conditions under which these reactions occur, how severe they are, and how they subside to alleviate patient concerns. Regarding the controversial issue of psychological side effects caused by ISO, researchers should shift their focus to the psychological problems that acne itself may cause.
RESUMEN
Background: Dengue has become an increasing public health threat around the world, and climate conditions have been identified as important factors affecting the transmission of dengue, so this study was aimed to establish a prediction model of dengue epidemic by meteorological methods. Methods: The dengue case information and meteorological data were collected from Guangdong Provincial Center for Disease Prevention and Control and Guangdong Meteorological Bureau, respectively. We used spatio-temporal analysis to characterize dengue epidemics. Spearman correlation analysis was used to analyze the correlation between lagged meteorological factors and dengue fever cases and determine the maximum lagged correlation coefficient of different meteorological factors. Then, Generalized Additive Models were used to analyze the non-linear influence of lagged meteorological factors on local dengue cases and to predict the number of local dengue cases under different weather conditions. Results: We described the temporal and spatial distribution characteristics of dengue fever cases and found that sporadic single or a small number of imported cases had a very slight influence on the dengue epidemic around. We further created a forecast model based on the comprehensive consideration of influence of lagged 42-day meteorological factors on local dengue cases, and the results showed that the forecast model has a forecast effect of 98.8%, which was verified by the actual incidence of dengue from 2005 to 2016 in Guangzhou. Conclusion: A forecast model for dengue epidemic was established with good forecast effects and may have a potential application in global dengue endemic areas after modification according to local meteorological conditions. High attention should be paid on sites with concentrated patients for the control of a dengue epidemic.
Asunto(s)
Dengue , Meteorología , China/epidemiología , Dengue/epidemiología , Humanos , Conceptos Meteorológicos , Salud PúblicaRESUMEN
Psoriasis is a chronic autoimmune inflammatory disease that remains active for a long period, even for life in most patients. The impact of psoriasis on health is not only limited to the skin, but also influences multiple systems of the body, even mental health. With the increasing of literature on the association between psoriasis and extracutaneous systems, a better understanding of psoriasis as an autoimmune disease with systemic inflammation is created. Except for cardiometabolic diseases, gastrointestinal diseases, chronic kidney diseases, malignancy, and infections that have received much attention, the association between psoriasis and more systemic diseases, including the skin system, reproductive system, and oral and ocular systems has also been revealed, and mental health diseases draw more attention not just because of the negative mental and mood influence caused by skin lesions, but a common immune-inflammatory mechanism identified of the two systemic diseases. This review summarizes the epidemiological evidence supporting the association between psoriasis and important and/or newly reported systemic diseases in the past 5 years, and may help to comprehensively recognize the comorbidity burden related to psoriasis, further to improve the management of people with psoriasis.
Asunto(s)
Psoriasis , Insuficiencia Renal Crónica , Enfermedad Crónica , Comorbilidad , Humanos , Inflamación/epidemiología , Insuficiencia Renal Crónica/epidemiología , Piel/patologíaRESUMEN
This study aimed to investigate the seasonal variation of gonorrhea in China, and to analyze the relationship between the incidence of gonorrhea and meteorological factors. Data from gonorrhea cases were obtained from the Disease Prevention and Control Bureau and the Data-Center for China Public Health Science, Chinese Center for Disease Control and Prevention, and the incidence of gonorrhea in China from 1 January 2006 to 31 December 2019 was analyzed. Meteorological data from the same period were obtained from the South China Meteorological Data Sharing Center, including the average monthly temperature, relative humidity, atmospheric pressure, sunshine hours, number of rainy days, and precipitation. The ratio-to-moving average method and seasonal subseries plots were used to analyze the seasonality of gonorrhea cases. The distributed lag non-linear model and attribution risks were used to investigate the effects of meteorological indexes on gonorrhea cases. The number of gonorrhea cases showed seasonal variation, with a peak in the third quarter and a decline in the first quarter. The Spearman assay showed that the reported number of patients with gonorrhea was positively correlated with the monthly temperature, relative humidity, precipitation, and number of rainy days. The risk of gonorrhea onset was highest at 6-11 °C, and the highest risk occurred when the average monthly temperature was 7 °C (resulting in an increase of 14.5% compared with 13 °C); a similar result was found regarding the cumulative risk of gonorrhea onset in relation to temperature. The attribution score of temperature to the onset of gonorrhea was 5.02% (95% confidence interval: - 3.84%, 13.88%). The study findings suggest that increased emphasis should be placed on screening for gonorrhea during summer and autumn, and that education on safe sexual behavior should be promoted during these times.
Asunto(s)
Gonorrea , China/epidemiología , Clima , Gonorrea/epidemiología , Humanos , Incidencia , Conceptos Meteorológicos , Estudios Retrospectivos , TemperaturaRESUMEN
[This corrects the article DOI: 10.3389/fimmu.2021.670153.].
RESUMEN
The root-associated actinobacteria play important roles in plant growth, nutrient use, and disease resistance due to their functional diversity. Salvia miltiorrhiza is a critical medicinal plant in China. The root actinobacterial community structure has been studied; however, the functions of root-associated actinobacteria of S. miltiorrhiza have not been elucidated. This study aimed to decipher the diversity and function of the culturable root-associated actinobacteria in plant growth using culture-dependent technology and culturable microbe metagenomes. We isolated 369 strains from the root-associated actinobacteria, belonging to four genera, among which Streptomyces was dominant. Besides, the functional prediction revealed some pathways related to plant growth, nitrogen and phosphorus metabolism, and antagonistic pathogens. We systematically described the diversity and functions of the culturable root-associated actinobacteria community. Our results demonstrated that the culturable root-associated actinobacteria of S. miltiorrhiza have rich functionalities, explaining the possible contribution of culturable root-associated actinobacteria to S. miltiorrhiza's growth and development. This study provides new insights into understanding the function of the culturable root-associated actinobacteria and can be used as a knowledge base for plant growth promoters and biological control agent development in agriculture.
RESUMEN
With the development of artificial intelligence, technique improvement of the classification of skin disease is addressed. However, few study concerned on the current classification system of International Classification of Diseases, Tenth Revision (ICD)-10 on Diseases of the skin and subcutaneous tissue, which is now globally used for classification of skin disease. This study was aimed to develop a new taxonomy of skin disease based on cytology and pathology, and test its predictive effect on skin disease compared to ICD-10. A new taxonomy (Taxonomy 2) containing 6 levels (Project 2-4) was developed based on skin cytology and pathology, and represents individual diseases arranged in a tree structure with three root nodes representing: (1) Keratinogenic diseases, (2) Melanogenic diseases, and (3) Diseases related to non-keratinocytes and non-melanocytes. The predictive effects of the new taxonomy including accuracy, precision, recall, F1, and Kappa were compared with those of ICD-10 on Diseases of the skin and subcutaneous tissue (Taxonomy 1, Project 1) by Deep Residual Learning method. For each project, 2/3 of the images were included as training group, and the rest 1/3 of the images acted as test group according to the category (class) as the stratification variable. Both train and test groups in the Projects (2 and 3) from Taxonomy 2 had higher F1 and Kappa scores without statistical significance on the prediction of skin disease than the corresponding groups in the Project 1 from Taxonomy 1, however both train and test groups in Project 4 had a statistically significantly higher F1-score than the corresponding groups in Project 1 (P = 0.025 and 0.005, respectively). The results showed that the new taxonomy developed based on cytology and pathology has an overall better performance on predictive effect of skin disease than the ICD-10 on Diseases of the skin and subcutaneous tissue. The level 5 (Project 4) of Taxonomy 2 is better on extension to unknown data of diagnosis system assisted by AI compared to current used classification system from ICD-10, and may have the potential application value in clinic of dermatology.
Asunto(s)
Inteligencia Artificial , Citodiagnóstico , Enfermedades de la Piel/diagnóstico , Piel/patología , Aprendizaje Profundo , Progresión de la Enfermedad , Humanos , Redes Neurales de la Computación , Piel/ultraestructura , Enfermedades de la Piel/clasificación , Enfermedades de la Piel/patologíaRESUMEN
Background: Myocardial macrophages have key roles in cardiac remodeling and dysfunction. The gamma-aminobutyric acid subtype A (GABAA) receptor was recently found to be distributed in macrophages, allowing regulation of inflammatory responses to various diseases. This study aimed to clarify the role of GABAA receptor-mediated macrophage responses in pressure overload-induced heart failure. Methods and Results: C57BL/6J mice underwent transverse aortic constriction for pressure-overload hypertrophy (POH) and were intraperitoneally treated with a specific GABAA receptor agonist (topiramate) or antagonist (bicuculline). Echocardiography, histology, and flow cytometry were performed to evaluate the causes and effects of myocardial hypertrophy and fibrosis. Activation of the GABAA receptor by topiramate reduced ejection fraction and fractional shortening, enlarged the end-diastolic and end-systolic left ventricular internal diameter, aggravated myocardial hypertrophy and fibrosis, and accelerated heart failure in response to pressure overload. Mechanistically, topiramate increased the number of Ly6Clow macrophages in the heart during POH and circulating Ly6Chigh classic monocyte infiltration in late-phase POH. Further, topiramate drove Ly6Clow macrophages toward MHCIIhigh macrophage polarization. As a result, Ly6Clow macrophages activated the amphiregulin-induced AKT/mTOR signaling pathway, and Ly6ClowMHCIIhigh macrophage polarization increased expression levels of osteopontin and TGF-ß, which led to myocardial hypertrophy and fibrosis. Conversely, GABAA receptor blockage with bicuculline reversed these effects. Conclusions: Control of the GABAA receptor activity in monocytes/macrophages plays an important role in myocardial hypertrophy and fibrosis after POH. Blockade of the GABAA receptor has the potential to improve pressure overload-induced heart failure.