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MOTIVATION: Virus mutation is one of the most important research issues which plays a critical role in disease progression and has prompted substantial scientific publications. Mutation extraction from published literature has become an increasingly important task, benefiting many downstream applications such as vaccine design and drug usage. However, most existing approaches have low performances in extracting virus mutation due to both lack of precise virus mutation information and their development based on human gene mutations. RESULTS: We developed ViMRT, a text-mining tool and search engine for automated virus mutation recognition using natural language processing. ViMRT mainly developed 8 optimized rules and 12 regular expressions based on a development dataset comprising 830 papers of 5 human severe disease-related viruses. It achieved higher performance than other tools in a test dataset (1662 papers, 99.17% in F1-score) and has been applied well to two other viruses, influenza virus and severe acute respiratory syndrome coronavirus-2 (212 papers, 96.99% in F1-score). These results indicate that ViMRT is a high-performance method for the extraction of virus mutation from the biomedical literature. Besides, we present a search engine for researchers to quickly find and accurately search virus mutation-related information including virus genes and related diseases. AVAILABILITY AND IMPLEMENTATION: ViMRT software is freely available at http://bmtongji.cn:1225/mutation/index.
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Minería de Datos , Virus , Minería de Datos/métodos , Mutación , Motor de Búsqueda , Virus/genéticaRESUMEN
BACKGROUND: Meteorin-like protein (METRNL)/Interleukin-41 (IL-41) is a novel immune-secreted cytokine/myokine involved in several inflammatory diseases. However, how METRNL exerts its regulatory properties on skin inflammation remains elusive. This study aims to elucidate the functionality and regulatory mechanism of METRNL in atopic dermatitis (AD). METHODS: METRNL levels were determined in skin and serum samples from patients with AD and subsequently verified in the vitamin D3 analogue MC903-induced AD-like mice model. The cellular target of METRNL activity was identified by multiplex immunostaining, single-cell RNA-seq and RNA-seq. RESULTS: METRNL was significantly upregulated in lesions and serum of patients with dermatitis compared to healthy controls (p <.05). Following repeated MC903 exposure, AD model mice displayed elevated levels of METRNL in both ears and serum. Administration of recombinant murine METRNL protein (rmMETRNL) ameliorated allergic skin inflammation and hallmarks of AD in mice, whereas blocking of METRNL signaling led to the opposite. METRNL enhanced ß-Catenin activation, limited the expression of Th2-related molecules that attract the accumulation of Arginase-1 (Arg1)hi macrophages, dendritic cells, and activated mast cells. CONCLUSIONS: METRNL can bind to KIT receptor and subsequently alleviate the allergic inflammation of AD by inhibiting the expansion of immune cells, and downregulating inflammatory gene expression by regulating the level of active WNT pathway molecule ß-Catenin.
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Molecular mechanisms of virus-related diseases involve multiple factors, including viral mutation accumulation and integration of a viral genome into the host DNA. With increasing attention being paid to virus-mediated pathogenesis and the development of many useful technologies to identify virus mutations (VMs) and viral integration sites (VISs), much research on these topics is available in PubMed. However, knowledge of VMs and VISs is widely scattered in numerous published papers which lack standardization, integration and curation. To address these challenges, we built a pilot database of human disease-related Virus Mutations, Integration sites and Cis-effects (ViMIC), which specializes in three features: virus mutation sites, viral integration sites and target genes. In total, the ViMIC provides information on 31 712 VMs entries, 105 624 VISs, 16 310 viral target genes and 1 110 015 virus sequences of eight viruses in 77 human diseases obtained from the public domain. Furthermore, in ViMIC users are allowed to explore the cis-effects of virus-host interactions by surveying 78 histone modifications, binding of 1358 transcription regulators and chromatin accessibility on these VISs. We believe ViMIC will become a valuable resource for the virus research community. The database is available at http://bmtongji.cn/ViMIC/index.php.
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Bases de Datos Factuales , Genoma Viral , Interacciones Huésped-Patógeno/genética , Programas Informáticos , Proteínas Virales/genética , Virosis/genética , Virus/genética , Cromatina/química , Cromatina/metabolismo , Minería de Datos , Regulación de la Expresión Génica , Histonas/genética , Histonas/metabolismo , Humanos , Internet , Mutación , Transducción de Señal , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Virales/metabolismo , Virosis/metabolismo , Virosis/patología , Virosis/virología , Integración Viral/genética , Virus/metabolismo , Virus/patogenicidadRESUMEN
Chronic exposure to harmful pollutants, chemicals, and pathogens from the environment can lead to pathological changes in the epithelial barrier, which increase the risk of developing an allergy. During allergic inflammation, epithelial cells send proinflammatory signals to group 2 innate lymphoid cell (ILC2s) and eosinophils, which require energy and resources to mediate their activation, cytokine/chemokine secretion, and mobilization of other cells. This review aims to provide an overview of the metabolic regulation in allergic asthma, atopic dermatitis (AD), and allergic rhinitis (AR), highlighting its underlying mechanisms and phenotypes, and the potential metabolic regulatory roles of eosinophils and ILC2s. Eosinophils and ILC2s regulate allergic inflammation through lipid mediators, particularly cysteinyl leukotrienes (CysLTs) and prostaglandins (PGs). Arachidonic acid (AA)-derived metabolites and Sphinosine-1-phosphate (S1P) are significant metabolic markers that indicate immune dysfunction and epithelial barrier dysfunction in allergy. Notably, eosinophils are promoters of allergic symptoms and exhibit greater metabolic plasticity compared to ILC2s, directly involved in promoting allergic symptoms. Our findings suggest that metabolomic analysis provides insights into the complex interactions between immune cells, epithelial cells, and environmental factors. Potential therapeutic targets have been highlighted to further understand the metabolic regulation of eosinophils and ILC2s in allergy. Future research in metabolomics can facilitate the development of novel diagnostics and therapeutics for future application.
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Hipersensibilidad , Humanos , Hipersensibilidad/metabolismo , Hipersensibilidad/inmunología , Animales , Eosinófilos/metabolismo , Eosinófilos/inmunología , Células Epiteliales/metabolismo , Células Epiteliales/inmunología , Inmunidad Innata , Dermatitis Atópica/inmunología , Dermatitis Atópica/metabolismo , Dermatitis Atópica/patología , Linfocitos/metabolismo , Linfocitos/inmunología , Rinitis Alérgica/metabolismo , Rinitis Alérgica/inmunologíaRESUMEN
Several traditional observational studies suggested an association between COVID-19 and leukocyte telomere length (LTL), a biomarker for biological age. However, whether there was a causal association between them remained unclear. We aimed to investigate whether genetically predicted COVID-19 is related to the risk of LTL, and vice versa. We performed bidirectional Mendelian randomization (MR) study using summary statistics from the genome-wide association studies of critically ill COVID-19 (n = 1 388 342) and LTL (n = 472 174) of European ancestry. The random-effects inverse-variance weighted estimation method was applied as the primary method with several other estimators as complementary methods. Using six single-nucleotide polymorphisms (SNPs) of genome-wide significance as instrumental variables for critically ill COVID-19, we did not find a significant association of COVID-19 on LTL (ß = 0.0075, 95% confidence interval [CI]: -0.018 to 0.021, p = 0.733). Likewise, using 97 SNPs of genome-wide significance as instrumental variables for LTL, we did not find a significant association of LTL on COVID-19 (odds ratio = 1.00, 95% CI: 0.79-1.28, p = 0.973). Comparable results were obtained using MR-Egger regression, weighted median, and weighted mode approaches. We did not find evidence to support a causal association between COVID-19 and LTL in either direction.
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COVID-19 , Estudio de Asociación del Genoma Completo , COVID-19/genética , Enfermedad Crítica , Humanos , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Telómero/genéticaRESUMEN
Thermohydrogen processing (THP) is an attractive technique that uses hydrogen as a temporary alloying element to modify the microstructure and properties of titanium alloys. However, the hydrogen diffusion behavior during THP is not fully understood owing to limited scope of methods to detect hydrogen distributions. Herein, we introduce neutron tomography as an efficient tool for three-dimensional (3D) hydrogen distribution analysis and quantitative determination in hydrogenated titanium alloys after THP. Thus motivated, a series of calibration samples of Ti-6Al-4V alloys with varying hydrogen contents were prepared and elaborated neutron tomography experiments and image data processing were performed. In this way, the 3D hydrogen distribution of the hydrogenated samples was obtained and the quantitative relationship between the hydrogen contents and the tomographic images was determined. To the best of our knowledge, this enabled for the first time the direct 3D visualization and characterization of the hydrogen distribution and concentration in titanium alloys after THP. It was deduced that hydrogen diffused from the surface to the interior of the hydrogenated sample in all directions during THP. In addition, the feasibility of neutron tomography for 3D quantitative hydrogen distribution was validated using continuous sample segmentation and the traditional heat conductivity method. Consequently, neutron tomography can be efficient for determining the hydrogen distribution and concentration in bulk metals and shed light on the hydrogen diffusion behavior and the mechanism of hydrogen-related materials and processing.
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The preparation and characterization of Al-Zn-Mg-Cu alloys with varying chemical compositions are helpful for rapid screening of the optimal compositions in the research and development of new materials. The traditional testing methods cannot accurately determine the composition gradient in samples because they have a low spatial resolution or are semi-quantitative and time-consuming. The micro X-ray fluorescence (µ-XRF) methodology has been used for the elemental imaging of Al-Zn-Mg-Cu alloys with varying chemical compositions. The experimental conditions, including testing voltages, testing currents and the dwell time for each pixel, were optimized systematically to improve the repeatability and accuracy of the µ-XRF methodology. The quantitative elemental imaging of an Al-Zn-Mg-Cu alloy rod sample using µ-XRF was performed, and the results were validated by conducting spark optical emission spectroscopy. The limits of detection of µ-XRF for Zn, Mg, and Cu were 0.007 wt%, 0.068 wt%, and 0.002 wt%, respectively. This versatile elemental imaging technique provided an effective means for the component analysis and process evaluation of alloy samples with a composition gradient and thus for research and development of new materials.
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BACKGROUND: Diverse studies have revealed discrepant evidence concerning the causal association between Corona Virus Disease 2019 (COVID-19) and COVID-19 vaccination in relation to migraines. Investigating the correlation between the former two factors and migraines can facilitate policymakers in the precise formulation of comprehensive post-pandemic interventions while urging the populace to adopt a judicious perspective on COVID-19 vaccination. METHODS: We undertook a Mendelian randomization (MR) study. The primary assessment of the causal relationship between the three different COVID-19 exposures and migraine was conducted using the standard inverse variance weighted (IVW) approach. In the supplementary analysis, we also employed two methodologies: the weighted median estimator (WME) and the MR-Egger regression. Ultimately, the reliability and stability of the outcomes were assessed via Cochran's Q test, the leave-one-out method, the MR-Egger intercept test, and the MR pleiotropy residual sum and outlier (MR-PRESSO) test. RESULTS: The results indicate an absence of correlation between genetically predicted COVID-19 (â Very severe respiratory confirmed COVID-19: odds ratio [OR], 1.0000881; 95%CI, 0.999748-1.000428; p = 0.6118; â¡Hospitalized COVID-19: OR, 1.000024; 95%CI, 0.9994893-1.000559; p = 0.931;â¢SARS-CoV-2 infection: OR, 1.000358; 95%CI, 0.999023-1.001695; p = 0.5993) and the risk of migraine. Furthermore, the MR-Egger regression and WME also yielded no evidence of COVID-19 elevating the risk of migraine occurrence. Sensitivity analysis affirmed the robustness and consistency of all outcomes. CONCLUSIONS: The results of this study do not offer genetic evidence to substantiate a causal relationship between COVID-19 and migraines. Thus, the deduction drawn from COVID-19 genetic data is that COVID-19 vaccination is unlikely to exert an impact on the occurrence of migraines, though this conclusion warrants further investigation.
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Vacunas contra la COVID-19 , COVID-19 , Trastornos Migrañosos , Vacunación , Humanos , COVID-19/complicaciones , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Análisis de la Aleatorización Mendeliana , Trastornos Migrañosos/etiología , Polimorfismo de Nucleótido Simple , Vacunación/efectos adversosRESUMEN
Psoriasis is an immuno-inflammatory disease characterized by excessive keratinocyte proliferation, requiring extensive lipids. 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1 (HMGCS1) is an essential enzyme in the mevalonate pathway, involved in cholesterol synthesis and the inflammatory response. However, the role of HMGCS1 in psoriasis has remained elusive. This study aims to elucidate the mechanism by which HMGCS1 controls psoriasiform inflammation. We discovered an increased abundance of HMGCS1 in psoriatic lesions when analyzing two Gene Expression Omnibus (GEO) datasets and confirmed this in psoriatic animal models and psoriatic patients by immunohistochemistry. In a TNF-α stimulated psoriatic HaCaT cell line, HMGCS1 was found to be overexpressed. Knockdown of HMGCS1 using siRNA suppressed the migration and proliferation of HaCaT cells. Mechanistically, HMGCS1 downregulation also reduced the expression of IL-23 and the STAT3 phosphorylation level. In imiquimod-induced psoriatic mice, intradermal injection of HMGCS1 siRNA significantly decreased the expression of HMGCS1 in the epidermis, which in turn led to an improvement in the Psoriasis Area and Severity Index score, epidermal thickening, and pathological Baker score. Additionally, expression levels of inflammatory cytokines IL-23, IL1-ß, chemokine CXCL1, and innate immune mediator S100A7-9 were downregulated in the epidermis. In conclusion, HMGCS1 downregulation improved psoriasis in vitro and in vivo through the STAT3/IL-23 axis.
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Hidroximetilglutaril-CoA Sintasa , Interleucina-23 , Queratinocitos , Psoriasis , Factor de Transcripción STAT3 , Animales , Femenino , Humanos , Masculino , Ratones , Línea Celular , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Células HaCaT , Hidroximetilglutaril-CoA Sintasa/metabolismo , Hidroximetilglutaril-CoA Sintasa/genética , Imiquimod , Interleucina-23/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Ratones Endogámicos BALB C , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Transducción de Señal/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genéticaRESUMEN
OBJECTIVE: To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula (4HF) and doxorubicin in triple-negative breast cancer (TNBC). METHODS: Murine-derived triple-negative mammary carcinoma cell line, 4T1 cells, was cultured and inoculated into mouse mammary glands. Sixty-six mice were randomly assigned into 6 groups (n=11 in ench): naïve, control, LD 4HF (low dose 4HF), HD 4HF (high dose 4HF), LD 4HF + D (low dose and doxorubicin), and D (doxorubicin). Apart from the naïve group, each mouse received subcutaneous inoculation with 5 × 105 4T1 cells resuspended in 100 µL of normal saline in the mammary fat pads. Starting from the day of tumor cell inoculation, tumors were grown for 6 days. The LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF, respectively. The LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin (5 mg/kg). The D group received weekly intraperitoneal injections of doxorubicin (5 mg/kg). The treatment naïve mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a week. The control group received daily oral gavage of 0.2 mL double-distilled water. The treatment period was 30 days. At the end of treatment, mice organs were harvested to analyze immunological activities via immunophenotyping, gene and multiplex analysis, histological staining, and gut microbiota analysis. RESULTS: Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens (P<0.05), altered the hypoxia and overall immune lymphocyte landscape, and manipulated gut microbiota to favor the anti-tumor immunological activities. Moreover, immunosuppressive genes, cytokines, and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated (P<0.05). 4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective in activating the anti-tumor immune response (P<0.05). CONCLUSION: The above results provide evidence for evaluating the immune regulating mechanisms of 4HF in breast cancer and support its clinical significance in its potential as an adjunctive therapeutic agent or immune supplement.
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Neoplasias , Solución Salina , Animales , Ratones , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Terapia Combinada , Inmunidad , Agua , Ratones Endogámicos BALB C , Línea Celular Tumoral , Neoplasias/tratamiento farmacológicoRESUMEN
OBJECTIVE: To assess the efficiency and the mechanism of fractional erbium:yttrium aluminum garnet (Er:YAG) laser for the treatment of morphea in mouse model. BACKGROUND: Morphea is a rare autoimmune disease characterized by excessive collagen deposition in skin. Fractional Er:YAG laser treatment is a promising treatment to improve morphea, despite limited studies about the therapeutic effect and underlying mechanism. METHODS: The mouse model of morphea was established by subcutaneously injecting with bleomycin (BLM). A total of 24 mice received fractional Er:YAG laser treatment once a week for 4 weeks. Objective measurement employed was ultrasonic imaging to measure dermal thickness. Subjective measures included scoring according to the adjusted Localized morphea Cutaneous Assessment Tool (LoSCAT); hematoxylin and eosin (H&E) staining to evaluate the histological grade of fibrosis; and quantitative morphometric studies to determine the expression of transforming growth factor-ß1 (TGF-ß1) and matrix metalloproteinase-1 (MMP1) by immunohistochemistry. RESULTS: In this self-controlled study, fractional Er:YAG laser treatment significantly ameliorate the severity of morphea, including lower clinical score (p < 0.01), decreased dermal thickness (p < 0.001), declined histological grade of fibrosis (p < 0.001), increased MMP1 (p < 0.001), and reduced TGF-ß1 (p < 0.01) expression. CONCLUSIONS: We found that fractional Er:YAG laser treatment of morphea has good clinical, ultrasonic, and histopathologic efficacy, which may be a promising treatment in the future.
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Láseres de Estado Sólido , Esclerodermia Localizada , Ratones , Animales , Láseres de Estado Sólido/uso terapéutico , Erbio , Factor de Crecimiento Transformador beta1 , Metaloproteinasa 1 de la Matriz , Fibrosis , AluminioRESUMEN
Cancer is a chronic disease that seriously endangers human health, and studies on its association with greenspace have been published. We aimed to systematically review the epidemiological evidence and obtain the best available evidence. PubMed, Web of Science, Embase, and Cochrane Library were used as search databases, the time limit was September 12, 2022, and the cited articles were manually supplemented. Two researchers independently performed literature screening and data extraction. We performed a meta-analysis of data using a normalized difference vegetation index (NDVI) as the greenspace measure, providing hazard ratio (HR) and corresponding 95% CI. After standardization of the data, we used a random effects model for pooling. We also assessed the risk of bias for each study and the quality of each evidence body. We identified 10,108 items and included 14 studies from 11 institutions in eight countries. All studies had a low risk of bias. Quantitative analysis of 13 studies found a beneficial association of greenspace with the mortality of lung cancer (pooled HR [95% CI]=0.965 [0.947, 0.983]) and prostate cancer (HR [95% CI]=0.939 [0.898, 0.980]) based on 0.1-unit NDVI increment and a potential beneficial association with the incidence of prostate, lung, and breast cancer. Greenspace had opposite associations with cancer mortality for urban and rural populations. Indirect comparisons did not find statistically significant differences in the effects of greenspace on different cancer outcomes. The evidence body assessment was considered to be "very low." This review indicated potential beneficial associations between greenspace for lung, prostate, and breast cancer outcomes. However, there was a lack of mediation analysis to explore the underlying mechanism of a causal association. Meanwhile, the interstudy heterogeneity was large. Therefore, future studies should consider more accurate exposure assessment and more comprehensive covariate coverage, while focusing on mediating analysis. PROSPERO: CRD42022361068.
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Neoplasias de la Mama , Parques Recreativos , Masculino , Humanos , Estudios de Cohortes , Causalidad , Modelos de Riesgos ProporcionalesRESUMEN
Introduction: Coronavirus disease 2019 (COVID-19) is increasing worldwide, with complications due to frequent viral mutations, an intricate pathophysiology, and variable host immune responses. Biomarkers with predictive and prognostic value are crucial but lacking. Methods: Serum samples from authentic and D614G variant (non-Omicron), and Omicron-SARS-CoV-2 infected patients were collected for METRNß detection and longitudinal cytokine/chemokine analysis. Correlation analyses were performed to compare the relationships between serum METRNß levels and cytokines/chemokines, laboratory parameters, and disease severity. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves were used to evaluate the predictive value of METRNß in COVID-19. Results: The serum level of METRNß was highly elevated in non-Omicron-SARS-CoV-2 infected patients compared to healthy individuals, and the non-survivor displayed higher METRNß levels than survivors among the critical ones. METRNß concentration showed positive correlation with viral load in NAPS. ROC curve showed that a baseline METRNß level of 1886.89 pg/ml distinguished COVID-19 patients from non-infected individuals with an AUC of 0.830. Longitudinal analysis of cytokine/chemokine profiles revealed a positive correlation between METRNß and pro-inflammatory cytokines such as IL6, and an inverse correlation with soluble CD40L (sCD40L). Higher METRNß was associated with increased mortality. These findings were validated in a second and third cohort of COVID-19 patients identified in a subsequent wave. Discussion: Our study uncovered the precise role of METRNß in predicting the severity of COVID-19, thus providing a scientific basis for further evaluation of the role of METRNß in triage therapeutic strategies.
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COVID-19 , Humanos , SARS-CoV-2 , Pronóstico , Biomarcadores , Citocinas , QuimiocinasRESUMEN
Functional explication of genes is of great scientific value. However, conventional methods have challenges for those genes that may affect biological processes but are not annotated in public databases. Here, we developed a novel explainable gene ontology fingerprint (XGOF) method to automatically produce knowledge networks on biomedical literature in a given field which quantitatively characterizes the association between genes and ontologies. XGOF provides systematic knowledge for the potential function of genes and ontologically compares similarities and discrepancies in different disease-XGOFs integrating omics data. More importantly, XGOF can not only help to infer major cellular components in a disease microenvironment but also reveal novel gene panels or functions for in-depth experimental research where few explicit connections to diseases have previously been described in the literature. The reliability of XGOF is validated in four application scenarios, indicating a unique perspective of integrating text and data mining, with the potential to accelerate scientific discovery.
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Localized scleroderma (LS) is an autoimmune disease with sclerosis of the skin as the main manifestation. Currently, there is no specific treatment for LS. The effectiveness of ablative fractional laser (AFL) therapy for LS has been demonstrated in several studies. Combining ablative fractional Er:YAG laser therapy with topical methotrexate may yield therapeutic benefits for patients with LS. To compare the efficacy and safety of AFL-assisted delivery of methotrexate in adults with LS, we randomly divided patients into an AFL therapy group and an ablative fractional laser-assisted delivery of methotrexate (AFL+MTX) therapy group. Laser and assisted drug delivery treatment were given every four weeks for four months, and 22 patients completed the trial. Ultrasound measurements of dermal thickness and histological fibrosis degree and the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) score were used to assess therapeutic effects. Treatment results showed that both AFL and AFL-assisted methotrexate delivery were effective in treating LS, and the laser combined with methotrexate therapy was more effective in improving clinical appearance (p value = 0.042) and dermal thickness (p value = 0.016). No serious adverse reaction occurred in either group. In conclusion, AFL and assisted delivery of methotrexate are effective and safe treatments for LS.
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The present work demonstrated the first-ever preparation of block specimens by the microwave sintering of H13 alloy powder. Varying proportions of vanadium powder (1.5%, 2.5%, 3.5%, 4.5%, and 5.5% on a mass basis) were added to H13 mold steel and these mixtures were sintered using microwaves. X-ray fluorescence spectroscopy was employed to determine the compositions of the resulting specimens and vanadium percentages of 1.56%, 2.04%, 3.10%, 4.06%, and 4.20% were determined. These results demonstrate a clear trend, with significantly lower vanadium amounts than expected based on the nominal values at higher vanadium loadings. Different samples were also found to exhibit different degrees of ablation, and this effect was related to the presence of voids in the materials. The surface compositions of these specimens were examined by laser-induced breakdown spectroscopy and were found to be relatively uniform. The microstructures as well as the hardness properties of the materials were assessed. Microwave sintering of 100 g specimens at 1300 °C for 10-min generated samples with hardness values ranging from 205 HV (at the lowest vanadium content) to 175.2 HV (at the highest vanadium content). The wear behavior of samples prepared by microwave sintering H13 die steel with different vanadium contents at room temperature has been studied. The results showed that 1.5% vanadium content is the best mass ratio.
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BACKGROUND: The interferon-inducible transmembrane (IFITM) proteins are localized in the endolysosomal and plasma membranes, conferring cellular immunity to various infections. However, the relationship with carcinogenesis remains poorly elucidated. In the present study, we investigated the role of IFITM in kidney renal clear cell carcinoma (KIRC). METHODS: We utilized the online databases of Oncomine, UALCAN and Human Protein Atlas to analyze the expression of IFITMs and validate their levels in human KIRC cells by qPCR and western blot. Furthermore, we evaluated prognostic significance with the Gene Expression Profiling Interactive Analysis tool (Kaplan-Meier (KM) Plotter) and delineated the immune cell infiltration profile related to IFITMs with the TIMER2.0 database. RESULTS: IFITMs were overexpressed in KIRC and varied in subtypes and tumor grades. High expression of IFITMs indicated a poor prognosis and more immune cell infiltration, especially endothelial cells and cancer-associated fibroblasts. IFITMs were associated with immune genes, which correlated with poor prognosis of renal clear cell carcinoma. We also explored the enriched network of IFITMs co-occurrence genes and their targeted transcription factors and miRNA. The expression of IFITMs correlated with hub mutated genes of KIRC. CONCLUSIONS: IFITMs play a crucial role in the oncogenesis of KIRC and could be a potential surrogate marker for treatment response to targeted therapies.
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The defective MEK/ERK signaling pathway and downstream hypomethylation pattern of lymphocytes are crucial for the pathogenesis of systemic lupus erythematosus (SLE). However, the role that the mesenchymal stem cells play in the MEK/ERK signaling pathway and DNA methylation of peripheral blood mononuclear cells (PBMC) from SLE patients remains unknown. In this study, we found that the MEK/ERK signaling pathway of PBMC from SLE patients was activated after the coculture with bone marrow-derived mesenchymal stem cells (BM-MSC) compared with that from the control group. In addition, the expression level of DNA methyltransferase 1 (DNMT1) increased while the levels of CD70, integrin, alpha L (ITGAL), selectin-l, and IL-13 were reduced in PBMC from SLE patients. However, no obvious effect of BM-MSC on PBMC from healthy controls was observed. These findings revealed that BM-MSC might downregulate the expression of methylation-sensitive genes and then suppress the autoactivated PBMC via the MEK/ERK signaling pathway. And it may be one of the mechanisms that BM-MSC ameliorated SLE.
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ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Metilación de ADN/genética , Leucocitos Mononucleares/metabolismo , Lupus Eritematoso Sistémico/enzimología , Lupus Eritematoso Sistémico/genética , Sistema de Señalización de MAP Quinasas , Células Madre Mesenquimatosas/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Técnicas de Cocultivo , HumanosRESUMEN
BACKGROUND: Healthcare workers are at high risk of developing hand eczema. This study aimed to investigate the association between occupational hygiene and self-reported hand eczema among nurses and doctors in Guangzhou. METHODS: A cross-sectional study using a self-administrated questionnaire sent to 740 health care workers in two tertiary hospitals between 1st April and 1st July 2019 was conducted. RESULTS: In total, 521 healthcare workers responded (70.4%). The prevalence of self-reported hand eczema was 9.6% [95% confidence interval (CI): 7.1-12.1%], with 10.8% in nurses and 6.9% in doctors. According to multivariable logistic regression analysis, the prevalence was higher in those who were excessively exposed to hair dye (OR: 3.871, 95% CI: 1.106-13.549) and those having a history of food allergy were at 3.013 (95% CI: 1.314-6.907) times greater risk of having hand eczema than those who did not. The odds of having hand eczema were 4.863 (95% CI: 1.037-22.803) times greater in those who hand washed more than 50 times daily in comparison to those who washed hands less than 10 times per day. The symptoms of hand eczema were mild during the investigation period. CONCLUSIONS: Hand eczema is common among healthcare workers in Guangzhou. The prevention of hand eczema by educational programs is needed for Chinese healthcare workers.
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Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that occurs between 1 in 6,000 and 1 in 10,000 live births. Additionally, renal angiomyolipoma is the most common form of renal disease in patients affected by TSC. Although a genetic mutation analysis of TSC is not rare, the correlation between the TSC gene mutation and renal angiomyolipoma phenotype is poorly understood. This study aims to analyze the mutation sites in 261 types of selected TSC patients. The results reveal that: (1) female patients develop more renal angiomyolipoma than male patients [p = 0.008, OR = 2.474, 95%CI (1.258-4.864)]; (2). The missense mutation of TSC1 led to a higher risk of renal angiomyolipoma [p < 0.01, OR = 15, 95%CI (2.859-78.691)], and in contrast, showed a reduced risk in patients with frameshift mutation [p = 0.03, OR = 0.252, 95%CI (0.07-0.912)]; (3). Patients with TSC2 mutations in the transcription activation domain 1 coding genes, had increased renal angiomyolipoma [p = 0.019, OR = 3.519, 95%CI (1.226-10.101)]. Therefore, our genotype-phenotype correlation study might shed light on the early monitoring and evaluation of renal angiomyolipoma in TSC patients.