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BACKGROUND: Numerous studies have documented significant alterations in the bodily fluids of Chronic Obstructive Pulmonary Disease (COPD) patients. However, existing literature lacks causal inference due to residual confounding and reverse causality. METHODS: Summary-level data for COPD were obtained from two national biobanks: the UK Biobank, comprising 1,605 cases and 461,328 controls, and FinnGen, with 6,915 cases and 186,723 controls. We also validated our findings using clinical data from 2,690 COPD patients and 3,357 healthy controls from the First Affiliated Hospital of Guangzhou Medical University. A total of 44 bodily fluid biomarkers were selected as candidate risk factors. Mendelian randomization (MR) and meta-analyses were used to evaluate the causal effects of these bodily fluids on COPD and lung function (FEV1/FVC). RESULTS: Mendelian randomization (MR) and meta-analyses, by integrating data from the UK Biobank and FinnGen cohort, found that 3 bodily fluids indicators (HDLC, EOS, and TP) were causally associated with the risk of COPD, two (EOS and TP) of which is consistent with our observational findings. Moreover, we noticed EOS and TP were causally associated with the risk of lung function (FEV1/FVC). CONCLUSIONS: The MR findings and clinical data highlight the independent and significant roles of EOS and TP in the development of COPD and lung function (FEV1/FVC), which might provide a deeper insight into COPD risk factors and supply potential preventative strategies.
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Líquidos Corporales , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Pulmón , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/genética , Factores de Riesgo , Estudio de Asociación del Genoma CompletoRESUMEN
Childhood leukemia is a prevalent form of pediatric cancer, with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) being the primary manifestations. Timely treatment has significantly enhanced survival rates for children with acute leukemia. This study aimed to develop an early and comprehensive predictor for hematologic malignancies in children by analyzing nutritional biomarkers, key leukemia indicators, and granulocytes in their blood. Using a machine learning algorithm and ten indices, the blood samples of 826 children with ALL and 255 children with AML were compared to a control group of 200 healthy children. The study revealed notable differences, including higher indicators in boys compared to girls and significant variations in most biochemical indicators between leukemia patients and healthy children. Employing a random forest model resulted in an area under the curve (AUC) of 0.950 for predicting leukemia subtypes and an AUC of 0.909 for forecasting AML. This research introduces an efficient diagnostic tool for early screening of childhood blood cancers and underscores the potential of artificial intelligence in modern healthcare.
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Inteligencia Artificial , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Niño , Masculino , Femenino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/diagnóstico , Preescolar , Adolescente , Lactante , Aprendizaje Automático , Pronóstico , Biomarcadores de Tumor/sangre , Estudios de Casos y ControlesRESUMEN
BACKGROUND: Our study aims to explore the relationship, shared gene signature, and the underlying mechanisms that connect rheumatoid arthritis (RA) to colorectal cancer (CRC). METHODS: Mendelian randomization (MR) analysis was conducted to assess the causality between RA and CRC. Summary statistic data-based Mendelian randomization (SMR) leveraging eQTL data was employed to identify the CRC-related causal genes. Integrated analyses of single-cell RNA sequencing and bulk RNA sequencing were employed to comprehensively investigate the shared gene signature and potential mechanisms underlying the pathogenesis of both RA and CRC. Predictive analysis of the shared hub gene in CRC immunotherapy response was performed. Pan-cancer analyses were conducted to explore the potential role of MYO9A in 33 types of human tumors. RESULTS: MR analysis suggested that RA might be associated with a slight increased risk of CRC (Odds Ratio = 1.04, 95% Confidence Interval = 1.01-1.07, P = 0.005). SMR analysis combining transcriptome analyses identified MYO9A as a causal gene in CRC and a shared gene signature in both RA and CRC. MYO9A may contribute to tumor suppression, while downregulation of MYO9A may impact CRC tumorigenesis by disrupting epithelial polarity and architecture, resulting in a worse prognosis in CRC. Additionally, MYO9A shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Pan-cancer analyses demonstrated MYO9A may have a protective role in the occurrence and progression of various human cancers. CONCLUSION: RA might be associated with a slight increased risk of CRC. MYO9A is a shared gene signature and a potential immune-related therapeutic target for both CRC and RA. Targeting the MYO9A-mediated loss of polarity and epithelial architecture could be a novel therapeutic approach for CRC.
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Artritis Reumatoide , Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Artritis Reumatoide/genética , Artritis Reumatoide/inmunología , Análisis de la Aleatorización Mendeliana , Miosinas/genética , Perfilación de la Expresión Génica , Transcriptoma , Sitios de Carácter Cuantitativo , Pronóstico , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , MultiómicaRESUMEN
The COVID-19 pandemic represents an unparalleled global public health crisis. Despite concerted research endeavours, the repertoire of effective treatment options remains limited. However, neutralising-antibody-based therapies hold promise across an array of practices, encompassing the prophylaxis and management of acute infectious diseases. Presently, numerous investigations into COVID-19-neutralising antibodies are underway around the world, with some studies reaching clinical application stages. The advent of COVID-19-neutralising antibodies signifies the dawn of an innovative and promising strategy for treatment against SARS-CoV-2 variants. Comprehensively, our objective is to amalgamate contemporary understanding concerning antibodies targeting various regions, including receptor-binding domain (RBD), non-RBD, host cell targets, and cross-neutralising antibodies. Furthermore, we critically examine the prevailing scientific literature supporting neutralising antibody-based interventions, and also delve into the functional evaluation of antibodies, with a particular focus on in vitro (vivo) assays. Lastly, we identify and consider several pertinent challenges inherent to the realm of COVID-19-neutralising antibody-based treatments, offering insights into potential future directions for research and development.
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COVID-19 , SARS-CoV-2 , Humanos , Anticuerpos Neutralizantes/uso terapéutico , COVID-19/terapia , Pandemias , Anticuerpos Antivirales/uso terapéuticoRESUMEN
INTRODUCTION: Chicken eggs and cow's milk are two of the most common foods that cause allergic reactions in infants and young children, and there is a lack of precise diagnostic methods to identify the allergic state of these patients. The recently developed food allergen component-resolved diagnosis (CRD) may be a more accurate diagnosis method for food allergies. METHODS: One hundred children sensitized to egg white and milk crude extracts and diagnosed with or suspected allergic disease were included. The specific immunoglobulin E (sIgE) (s) of animal food allergen crude extracts (egg yolk, milk, shrimp, crab, cod, beef) and the main components of egg white and milk were tested. The sensitization characteristics, cross-reactivity, and clinical relevance were analyzed. RESULTS: The results of egg white-sensitized patients showed that ovalbumin (Gal d 2) had the highest positive rate of 100%. Compared with other pairwise combinations of egg allergens, the combination of egg white and Gal d 2 had higher diagnostic accuracy, with an AUC of 0.876 (95% CI: 0.801-0.951), a sensitivity of 88.9%, and a specificity of 75.9%. The positive rates of beta-lactoglobulin (Bos d 5) and alpha-lactoglobulin (Bos d 4) in the milk-sensitized children were comparable, 92% and 91%, respectively. The combination of crude milk extract and Bos d 4 had the highest diagnostic accuracy, with an AUC of 0.969 (95% CI: 0.938-0.999), a sensitivity of 100%, and a specificity of 82.7%. CONCLUSION: Among these subjects, our study found the main allergenic component of egg white was Gal d 2, and the main allergenic components of milk were Bos d 4 and Bos d 5. CRD may help identify egg/milk allergies and non-allergies.
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Hipersensibilidad al Huevo , Hipersensibilidad a los Alimentos , Hipersensibilidad a la Leche , Animales , Femenino , Bovinos , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad al Huevo/diagnóstico , Hipersensibilidad a la Leche/diagnóstico , Alérgenos , China/epidemiologíaRESUMEN
Background: SARS-CoV-2 induces apoptosis and amplifies the immune response by continuously stressing the endoplasmic reticulum (ER) after invading cells. This study aimed to establish a protein-metabolic pathway associated with ER dysfunction based on the invasion mechanism of SARS-CoV-2. Methods: This study included 17 healthy people and 46 COVID-19 patients, including 38 mild patients and 8 severe patients. Proteomics and metabolomics were measured in the patient plasma collected at admission and one week after admission. The patients were further divided into the aggravation and remission groups based on disease progression within one week of admission. Results: Cross-sectional comparison showed that endoplasmic reticulum molecular chaperone-binding immunoglobulin protein (ERC-BiP), angiotensinogen (AGT), ceramide acid (Cer), and C-reactive protein (CRP) levels were significantly increased in COVID-19 patients, while the sphingomyelin (SM) level was significantly decreased (P < 0.05). In addition, longitudinal comparative analysis found that the temporal fold changes of ERC-BiP, AGT, Cer, CRP, and SM were significantly different between the patients in the aggravation and remission groups (P < 0.05). ERC-BiP, AGT, and Cer levels were significantly increased in aggravation patients, while SM was significantly decreased (P < 0.05). Meanwhile, ERC-BiP was significantly correlated with AGT (r = 0.439; P < 0.001). Conclusions: ERC-BiP can be used as a core index to reflect the degree of ER stress in COVID-19 patients, which is of great value for evaluating the functional state of cells. A functional pathway for AGT/ERC-BiP/glycolysis can directly assess the activation of unfolded protein reactions. The ERC-BiP pathway is closer to the intracellular replication pathway of SARS-CoV-2 and may help in the development of predictive protocols for COVID-19 exacerbation.
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With the global prevalence of COVID-19 and the constant emergence of viral variants, boosters for COVID-19 vaccines to enhance antibody titers in human bodies will become an inevitable trend. However, there is a lack of data on antibody levels and the protective effects of booster injections. This study monitored and analyzed the antibody potency and the antibody responses induced by the booster injection in the subjects who received three vaccine doses. The study was conducted in a multicenter collaboration and recruited 360 healthy adults aged 20-74. Participants received the first, second, and booster doses of inactivated Sinopharm/BBIBP COVID-19 vaccine at 0, 1, and 7 months. Vaccine-induced virus-specific antibody levels (SARS-COV-2-IgA/IgM/IgG) were monitored at multiple time points, surrogate virus neutralization test (sVNT), and the spatial distribution and proportion of immune cells and markers were analyzed using the CyTOF method before vaccination and a month after the second dose. The titers of SARS-CoV-2-IgA/IgM/IgG and neutralizing antibodies increased to a high level in the first month after receiving the second dose of vaccine and declined slowly after that. The antibody levels of SARS-CoV-2-IgG and sVNT were significantly increased at 0.5 months after the induction of the booster (p < 0.05). Despite a downward trend, the antibody levels were still high in the following 6 months. The B cell concentration (in humoral sample) a month after the second injection was significantly reduced compared to that before the vaccine injection (p < 0.05). The proportion of the C01 cell cluster was significantly decreased compared with that before vaccine injection (p < 0.05). Individual cell surface markers showed distinctions in spatial distribution but were not significantly different. This study has shown that serum antibody titer levels will decrease with time by monitoring and analyzing the antibody efficacy and the antibody reaction caused by the booster injection of healthy people who received the whole vaccination (completed three injections). Still, the significant peak of the antibody titer levels after booster highlights the recall immune response. It can maintain a high concentration of antibody levels for a long time, which signifies that the protection ability has been enhanced following the injection of booster immunization. Additionally, CyTOF data shows the active production of antibodies and the change in the immunity environment.
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COVID-19 , Vacunas , Adulto , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Inmunoensayo , Inmunoglobulina A , Inmunoglobulina G , Inmunoglobulina M , SARS-CoV-2RESUMEN
BACKGROUND: The inactivated Sinopharm/BBIBP COVID-19 vaccine has been widely used in the world and has joined the COVAX vaccine supply program for developing countries. It is also well adapted for usage in low- and middle-income nations due to their low storage requirements. OBJECTIVE: This study aims to report on the kinetics, durability, and neutralizing ability of the induced immunity of the BBIBP vaccine, and the intensified antibody response elicited by the booster. METHODS: A total of 353 healthy adult participants, aged 20-74 years, were recruited in this multicenter study. A standard dose of the BBIBP vaccine was administered (Month 0), followed by a second standard dose (Month 1), and a booster dose (after Month 7). Vaccine-induced virus-specific antibody levels (SARS-CoV-2-IgA/IgM/IgG), conventional virus neutralization test (cVNT), pseudovirus neutralization test (pVNT), and surrogate virus neutralization test (sVNT) were monitored over multiple time points. RESULTS: Neutralizing titers induced by the two doses of inactivated vaccine for COVID-19 peaked at Month 2 and declined to 33.89% at Month 6. Following the booster dose, elevated levels of antibodies were induced for IgA, IgG, and neutralizing antibodies, with neutralizing titer reaching 13.2 times that of before the booster. CONCLUSION: By monitoring the antibody titer levels postvaccination, this study has shown that serum antibody levels will decrease over time, but a notable spike in antibody levels postbooster highlights the anamnestic immune response. This signifies that the protection capability has increased following the injection of booster immunization.
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Vacunas contra la COVID-19 , COVID-19 , Adulto , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Humanos , Inmunidad Humoral , Inmunización Secundaria , Inmunoglobulina A , Inmunoglobulina G , SARS-CoV-2 , VacunaciónRESUMEN
The newly identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a global health emergency (COVID-19) because of its rapid spread and high mortality. Since the virus epidemic, many pathogenic mechanisms have been revealed, and virus-related vaccines have been successfully developed and applied in clinical practice. However, the pandemic is still developing, and new mutations are still emerging. Virus pathogenicity is closely related to the immune status of the host. As innate immunity is the body's first defense against viruses, understanding the inhibitory effect of SARS-CoV-2 on innate immunity is of great significance for determining the target of antiviral intervention. This review summarizes the molecular mechanism by which SARS-CoV-2 escapes the host immune system, including suppressing innate immune production and blocking adaptive immune priming. Here, on the one hand, we devoted ourselves to summarizing the combined action of innate immune cells, cytokines, and chemokines to fine-tune the outcome of SARS-CoV-2 infection and the related immunopathogenesis. On the other hand, we focused on the effects of the SARS-CoV-2 on innate immunity, including enhancing viral adhesion, increasing the rate of virus invasion, inhibiting the transcription and translation of immune-related mRNA, increasing cellular mRNA degradation, and inhibiting protein transmembrane transport. This review on the underlying mechanism should provide theoretical support for developing future molecular targeted drugs against SARS-CoV-2. Nevertheless, SARS-CoV-2 is a completely new virus, and people's understanding of it is in the process of rapid growth, and various new studies are also being carried out. Although we strive to make our review as inclusive as possible, there may still be incompleteness.
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COVID-19 , SARS-CoV-2 , Antivirales/farmacología , Citocinas/metabolismo , Humanos , Inmunidad InnataRESUMEN
The sudden emergence of the SARS-CoV-2 Omicron variant is causing major global concern due to its high number of mutations compared to previous variants, which is a relatively rare but significant event that can change the course of viral evolution, the occurrence of which might have huge consequences for the natural evolution of species in general, prompting us to rethink our knowledge on evolution.
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COVID-19 , SARS-CoV-2 , Humanos , Mutación , SARS-CoV-2/genéticaRESUMEN
BACKGROUND: Higher detection of interstitial pneumonia with autoimmune features (IPAF), and idiopathic pulmonary fibrosis (IPF), has significant diagnostic and therapeutic implications. Some matrix metalloproteinases (MMPs) have become reliable diagnostic biomarkers in IPAF and IPF in previous studies, yet relevant reliability remains to be recognized. MATERIALS AND METHODS: In this study, 36 ILDs patients, including 31 IPAF patients (Mean ± SD, 50.20 ± 5.10 years; 16 [51.6%] females) and five IPF patients (Mean ± SD, 61.20 ± 6.73 years; one [20.0%] females) were retrospectively enrolled. Serial serum samples were collected from patients with IPAF and IPF between January 2019 and December 2020. Notably, Serum MMPs levels were measured by U-PLEX Biomarker Group 1(Human) Multiplex Assays (MSD, USA). RESULTS: A combination of MMPs and combinatorial biomarkers was strongly associated with clinical subjects in this study (AUC, 0.597 for Stability vs. Improvement and 0.756 for Stability vs. Exacerbation). Importantly, the AUC of MMP-12 reaches 0.730 (p < 0.05, Stability AUC vs. Improvement AUC) while MMP-13 reaches 0.741 (p < 0.05, Stability AUC vs. Exacerbation AUC) showed better performance than other MMPs in two comparisons. CONCLUSIONS: Clinical risk factors and MMPs are strongly associated with either stratification of the disease of progression of IPAF or in two IPAF and IPF independent cohorts. To our knowledge, this is the first to illustrate that MMP-12 and MMP-13 may be expected to become typical promising biomarkers in Improvement - IPAF and Exacerbation - IPAF, respectively.
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Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales , Femenino , Humanos , Masculino , Biomarcadores , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/complicaciones , Metaloproteinasa 12 de la Matriz , Metaloproteinasa 13 de la Matriz , Reproducibilidad de los Resultados , Estudios Retrospectivos , Persona de Mediana Edad , AncianoRESUMEN
There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.
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Betacoronavirus/clasificación , Betacoronavirus/fisiología , Infecciones por Coronavirus/epidemiología , Pandemias/estadística & datos numéricos , Neumonía Viral/epidemiología , Animales , COVID-19 , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Manejo de la Enfermedad , Guías como Asunto/normas , Humanos , Pandemias/prevención & control , Neumonía Viral/patología , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , SARS-CoV-2 , Organización Mundial de la SaludRESUMEN
The metallic fixations used in surgical procedures to support the spine mechani-cally usually consist of high-density materials. Radiation therapy to palliate spinal cord compression can include prophylactic inclusion of potential tumor around the site of such fixation devices. Determination of the correct density and shape of the spine fixation device has a direct effect on the dose calculation of the radiation field. Even with the application of modern computed tomography (CT), under- or overestimation of dose, both immediately next to the device and in the surround-ing tissues, can occur due to inaccuracies in the dose prediction algorithm. In this study, two commercially available dose prediction algorithms (Eclipse AAA and ACUROS), EGSnrc Monte Carlo, and GAFchromic film measurements were com-pared for a clinical spine SBRT case to determine their accuracy. An open six-field plan and a clinical nine-field IMRT plan were applied to a phantom containing a metal spine fixation device. Dose difference and gamma analysis were performed in and around the tumor region adjacent to the fixation device. Dose calculation inconsistency was observed in the open field plan. However, in the IMRT plan, the dose perturbation effect was not observed beyond 5 mm. Our results suggest that the dose effect of the metal fixation device to the spinal cord and the tumor volume is not observable, and all dose calculation algorithms evaluated can provide clinically acceptable accuracy in the case of spinal SBRT, with the tolerance of 95% for gamma criteria of 3%/3 mm.
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Algoritmos , Metales/química , Fantasmas de Imagen , Radiocirugia/instrumentación , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Neoplasias de la Columna Vertebral/cirugía , Simulación por Computador , Humanos , Método de Montecarlo , Radiocirugia/métodos , Dosificación Radioterapéutica , Tomografía Computarizada por Rayos XRESUMEN
Our research aimed to identify new therapeutic targets for Lung adenocarcinoma (LUAD), a major subtype of non-small cell lung cancer known for its low 5-year survival rate of 22%. By employing a comprehensive methodological approach, we analyzed bulk RNA sequencing data from 513 LUAD and 59 non-tumorous tissues, identifying 2,688 differentially expressed genes. Using Mendelian randomization (MR), we identified 74 genes with strong evidence for a causal effect on risk of LUAD. Survival analysis on these genes revealed significant differences in survival rates for 13 of them. Our pathway enrichment analysis highlighted their roles in immune response and cell communication, deepening our understanding. We also utilized single-cell RNA sequencing (scRNA-seq) to uncover cell type-specific gene expression patterns within LUAD, emphasizing the tumor microenvironment's heterogeneity. Pseudotime analysis further assisted in assessing the heterogeneity of tumor cell populations. Additionally, protein-protein interaction (PPI) network analysis was conducted to evaluate the potential druggability of these identified genes. The culmination of our efforts led to the identification of five genes (tier 1) with the most compelling evidence, including SECISBP2L, PRCD, SMAD9, C2orf91, and HSD17B13, and eight genes (tier 2) with convincing evidence for their potential as therapeutic targets.
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Background: Sepsis is a major contributor to global morbidity and mortality, affecting millions each year. Notwithstanding the decline in sepsis incidence and mortality over decades, gender disparities in sepsis outcomes persist, with research suggesting higher mortality rates in males. Methods: This retrospective study aims to delineate gender-specific clinical biomarker profiles impacting sepsis progression and mortality by examining sepsis cases and related clinical data from the past three years. Propensity score matching was used to select age-matched healthy controls for comparison. Results: Among 265 sepsis patients, a significantly higher proportion were male (60.8%, P<0.001). While mortality did not significantly differ by gender, deceased patients were significantly older (mean 69 vs 43 years, P=0.003), more likely to have hypertension (54% vs 25%, P=0.019), and had higher SOFA scores (mean ~10 vs 4, P<0.01) compared to survivors. Principal Component Analysis (PCA) showed clear separation between sepsis patients and healthy controls. 48 serum biomarkers were significantly altered in sepsis, with Triiodothyronine, Apolipoprotein A, and Serum cystatin C having the highest diagnostic value by ROC analysis. Gender-stratified comparisons identified male-specific (e.g. AFP, HDLC) and female-specific (e.g. Rheumatoid factor, Interleukin-6) diagnostic biomarkers. Deceased patients significantly differed from survivors, with 22 differentially expressed markers; Antithrombin, Prealbumin, HDL cholesterol, Urea nitrogen and Hydroxybutyrate had the highest diagnostic efficiency for mortality. Conclusion: These findings enhance our understanding of gender disparities in sepsis and may guide future therapeutic strategies. Further research is warranted to validate these biomarker profiles and investigate the molecular mechanisms underlying these gender differences in sepsis outcomes.
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Biomarcadores , Sepsis , Humanos , Sepsis/mortalidad , Sepsis/sangre , Sepsis/diagnóstico , Masculino , Femenino , Biomarcadores/sangre , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Factores Sexuales , Adulto , Anciano de 80 o más AñosRESUMEN
During the persistent COVID-19 pandemic, the swift progression of acute myocarditis has emerged as a profound concern due to its augmented mortality, underscoring the urgency of prompt diagnosis. This study analyzed blood samples from 5,230 COVID-19 individuals, identifying key blood and myocardial markers that illuminate the relationship between COVID-19 severity and myocarditis. A predictive model, applying Bayesian and random forest methodologies, was constructed for myocarditis' early identification, unveiling a balanced gender distribution in myocarditis cases contrary to a male predominance in COVID-19 occurrences. Particularly, older men exhibited heightened vulnerability to severe COVID-19 strains. The analysis revealed myocarditis was notably prevalent in younger demographics, and two subvariants COVID-19 progression paths were identified, characterized by symptom intensity and specific blood indicators. The enhanced myocardial marker model displayed remarkable diagnostic accuracy, advocating its valuable application in future myocarditis detection and treatment strategies amidst the COVID-19 crisis.
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Background: Recent studies have linked atopic dermatitis (AD) to colorectal cancer (CRC) risk. Their causality and potential molecular mechanisms remain unclear. Methods: We performed Mendelian randomization (MR) analysis to evaluate the causality between AD and CRC. Summary statistic data-based Mendelian randomization (SMR) analysis was used to identify CRC-related causal genes. Transcriptome analyses and immunohistochemical methods were applied to investigate the shared gene signature and potential mechanisms that contribute to the pathogenesis of both AD and CRC. A predictive analysis was performed to examine the shared gene signature associated with immunotherapy response in CRC. Results: MR analysis indicated a causal association between AD and a decreased risk of CRC. SMR analysis uncovered TET2 as a CRC-related causal gene, showing an inverse relationship with the risk of CRC. Transcriptome analyses identified TET2 as a shared gene signature between AD and CRC. Decreased TET2 expression is associated with impaired demethylation and worse prognosis in CRC patients. We observed ten pathways related to the inflammatory response and immune regulation that may be shared mechanisms underlying both AD and CRC. These findings were validated through single-cell analysis. TET2 shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Conclusion: There is a causal association between AD and a decreased risk of CRC. AD may influence the occurrence of CRC by modulating immune and inflammatory responses. TET2 could serve as a potential biomarker for prognosis and may be considered a novel therapeutic target for methylation and immune-related interventions.