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BACKGROUNDThe level of nasal spike-specific secretory IgA (sIgA) is inversely correlated with the risk of SARS-CoV-2 Omicron infection. This study aimed to evaluate the safety and immunogenicity of intranasal vaccination using Ad5-S-Omicron (NB2155), a replication-incompetent human type 5 adenovirus carrying Omicron BA.1 spike.METHODSAn open-label, single-center, investigator-initiated trial was carried out on 128 health care workers who had never been infected with SARS-CoV-2 and had previously received 2 or 3 injections of inactivated whole-virus vaccines, with the last dose given 3-19 months previously (median 387 days, IQR 333-404 days). Participants received 2 intranasal sprays of NB2155 at 28-day intervals between November 30 and December 30, 2022. Safety was evaluated by solicited adverse events and laboratory tests. The elevation of nasal mucosal spike-specific sIgA and serum neutralizing activities were assessed. All participants were monitored for infection by antigen tests, disease symptoms, and the elevation of nucleocapsid-specific sIgA in the nasal passage.RESULTSThe vaccine-related solicited adverse events were mild. Nasal spike-specific sIgA against 10 strains had a mean geometric mean fold increase of 4.5 after the first dose, but it increased much higher to 51.5 after the second dose. Serum neutralizing titers also increased modestly to 128.1 (95% CI 74.4-220.4) against authentic BA.1 and 76.9 (95% CI 45.4-130.2) against BA.5 at 14 days after the second dose. Due to the lifting of the zero-COVID policy in China on December 7, 2022, 57.3% of participants were infected with BA.5 between days 15 and 28 after the first dose, whereas no participants reported having any symptomatic infections between day 3 and day 90 after the second dose. The elevation of nasal nucleocapsid-specific sIgA on days 0, 14, 42, and 118 after the first dose was assessed to verify that these 2-dose participants had no asymptomatic infections.CONCLUSIONA 2-dose intranasal vaccination regimen using NB2155 was safe, was well tolerated, and could dramatically induce broad-spectrum spike-specific sIgA in the nasal passage. Preliminary data suggested that the intranasal vaccination may establish an effective mucosal immune barrier against infection and warranted further clinical studies.TRIAL REGISTRATIONChinese Clinical Trial Registry (ChiCTR2300070346).FUNDINGNatural Science Foundation of China, Guangzhou Laboratory, The First Affiliated Hospital of Guangzhou Medical University.
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Vacinas contra COVID-19 , COVID-19 , Imunidade nas Mucosas , Imunoglobulina A Secretora , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenoviridae , Administração Intranasal , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , COVID-19/prevenção & controle , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Vetores Genéticos/administração & dosagem , Imunoglobulina A Secretora/imunologia , Mucosa Nasal/imunologia , Mucosa Nasal/virologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação/métodosRESUMO
Background: While serum periostin and Krebs von den Lungen-6 (KL-6) have been acknowledged as independent markers in idiopathic pulmonary fibrosis (IPF) diagnosis, the clinical combinatory potential of these biomarkers combined with high-resolution computed tomography (HRCT) has yet to be fully explored. Methods: This retrospective study involved 78 participants, comprising 51 UIP-IPF patients and 27 healthy controls. All subjects underwent clinical and laboratory examinations, particularly the detection of periostin and KL-6 using ELISA with innovative HRCT fibrosis score evaluations at admission and discharge during hospitalization in UIP-IPF patients. Results: In our cohort of patients with IPF, predominantly male, over an average follow-up period of 195.27 days. Serum levels of periostin and KL-6 were significantly elevated in IPF patients compared to healthy controls (*p < 0.05). Post-treatment, KL-6 levels decreased significantly, while periostin levels increased. Notably, periostin exhibited superior prognostic accuracy over KL-6, with a higher AUC of 0.875 than 0.639 in ROC analysis. An increase in periostin levels correlated with disease progression, as evidenced by worsened HRCT fibrotic scores and decreased survival probability. These findings underscore periostin's potential as a reliable biomarker for assessing IPF severity and therapeutic response. Conclusion: Our findings underscore the preeminence of serum periostin over KL-6 in UIP-IPF diagnosis, particularly when conjoined with HRCT fibrosis score.
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BACKGROUND: Lung cancer (LC), a paramount global life-threatening condition causing significant mortality, is most commonly characterized by its subtype, lung adenocarcinoma (LUAD). Concomitant with LC, pulmonary fibrosis (PF) and interstitial lung disease (ILD) contribute to an intricate landscape of respiratory diseases. Idiopathic pulmonary fibrosis (IPF) in association with LC has been explored. However, other fibrotic interrelations remain underrepresented, especially for LUAD-PF and LUAD-ILD. METHODS: We analysed data with statistical analysis from 7,137 healthy individuals, 7,762 LUAD patients, 7,955 ILD patients, and 2,124 complex PF patients collected over ten years. Furthermore, to identify blood indicators related to lung disease and its complications and compare the relationships between different indicators and lung diseases, we successfully applied the naive Bayes model for a biomarker-based prediction of diagnosis and development into complex PF. RESULTS: Males predominantly marked their presence in all categories, save for complex PF where females took precedence. Biomarkers, specifically AGR, MLR, NLR, and PLR emerged as pivotal in discerning lung diseases. A machine-learning-driven predictive model underscored the efficacy of these markers in early detection and diagnosis, with NLR exhibiting unparalleled accuracy. CONCLUSIONS: Our study elucidates the gender disparities in lung diseases and illuminates the profound potential of serum biomarkers, including AGR, MLR, NLR, and PLR in early lung cancer detection. With NLR as a standout, therefore, this study advances the exploration of indicator changes and predictions in patients with pulmonary disease and fibrosis, thereby improving early diagnosis, treatment, survival rate, and patient prognosis.
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Adenocarcinoma de Pulmão , Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Feminino , Masculino , Detecção Precoce de Câncer/métodos , Adenocarcinoma de Pulmão/sangue , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Pessoa de Meia-Idade , Idoso , Fibrose Pulmonar/sangue , Fibrose Pulmonar/diagnóstico , Aprendizado de Máquina , Prognóstico , Biomarcadores Tumorais/sangue , Teorema de Bayes , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/diagnóstico , Fibrose Pulmonar Idiopática/sangue , Fibrose Pulmonar Idiopática/diagnóstico , AdultoRESUMO
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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Inteligência Artificial , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Criança , Masculino , Feminino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/diagnóstico , Pré-Escolar , Adolescente , Lactente , Aprendizado de Máquina , Prognóstico , Biomarcadores Tumorais/sangue , Estudos de Casos e ControlesRESUMO
Background: Water, sanitation, and hygiene (WaSH) are crucial determinants of human health. However, the spatio-temporal trends in the global burden of disease attributable to unsafe WaSH remain poorly understood. This study aimed to estimate the disease burden attributable to unsafe WaSH from 1990 to 2019 using data from the Global Burden of Disease (GBD) Study 2019, providing new insights into the associated health conditions. Methods: We extracted data on deaths and disability-adjusted life years (DALYs) attributable to unsafe WaSH from 1990 to 2019 from the GBD 2019. The disease burden was evaluated by region, sociodemographic index (SDI), sex, age, risk factor, and specific disease. Results: Globally, unsafe WaSH was responsible for 1 656 887.37 (95% uncertainty interval (UI) = 1 198 864.94, 2 312 688.33) deaths in 2019, a 49% decrease from 1990. The global age-standardised DALY rate due to unsafe WaSH was 1244.29 (95% UI = 993.20, 1544.13) per 100 000 in 2019, a 66% reduction since 1990. Western sub-Saharan Africa had the highest age-standardised death rate (ASDR) and age-standardised DALY rate in both 1990 and 2019. Among the 21 regions studied, only high-income North America witnessed an increasing ASDR from 1990 to 2019. Countries and territories in low SDI regions had higher ASDRs and age-standardised DALY rates. U-shaped associations were observed between the estimated annual percentage change (EAPC) of ASDR, EAPC of age-standardised DALY rate, and SDI. Both rates were slightly lower in females, with the burden concentrated in those under five and over 80 years old. In 2019, unsafe water source and diarrhoeal diseases remained the leading risk factor and cause of unsafe WaSH-related disease burden, respectively. Conclusions: Despite substantial improvements in hygiene awareness and health education, unsafe WaSH persists as a significant global health risk and a major contributor to the burden of diarrhoeal diseases. Disparities across regions and age groups remain evident. Increased efforts are needed to raise awareness and strengthen water and sanitation infrastructure, particularly in low SDI settings, to mitigate the health risks associated with unsafe WaSH.
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Carga Global da Doença , Saúde Global , Desinfecção das Mãos , Saneamento , Humanos , Saúde Global/estatística & dados numéricos , Feminino , Masculino , Adulto , Abastecimento de Água , Pessoa de Meia-Idade , Pré-Escolar , Lactente , Adolescente , Criança , Idoso , Adulto Jovem , Higiene , Anos de Vida Ajustados por DeficiênciaRESUMO
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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In this editorial, we comment on an article by Alhammad et al that was published in a recent issue of the World Journal of Clinical Cases (Manuscript No.: 91134). We specifically focus on the mental health problems caused by coronavirus disease 2019 (COVID-19), their mechanisms, and targeted rehabilitation strategies. Severe acute respiratory syndrome coronavirus 2, via its spike protein, binds to angiotensin-converting enzyme 2 and other receptors prior to infiltrating diverse cells within the central nervous system, including endothelial cells, neurons, astrocytes, and oligodendrocytes, thereby contributing to the development of mental illnesses. Epidemiological data from 2020 underscored the global upsurge in major depressive and anxiety disorders by 27.6% and 25.6%, respectively, during the pandemic. The commented research show that 30% of post-intensive care unit discharge patients with COVID-19 in the Arabic region exhibited Hospital Anxiety and Depression Scale scores that were indicative of anxiety and depression. While acknowledging psychosocial factors, such as grief and loss, it is crucial to recognize the potential neurological impact of the virus through various mechanisms. Accordingly, interventions that encompass dietary measures, health supplements, and traditional Chinese medicine with neuroprotective properties are necessary. This editorial underscores the urgency to implement comprehensive rehabilitation approaches to address the intricate interplay between COVID-19 and mental well-being.
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Evidence on the link of long-term exposure to ozone (O3) with childhood asthma, rhinitis, conjunctivitis and eczema is inconclusive. We did a population-based cross-sectional survey, including 177,888 children from 173 primary and middle schools in 14 Chinese cities. A satellite-based spatiotemporal model was employed to assess four-year average O3 exposure at both residential and school locations. Information on asthma, allergic rhinitis, eczema and conjunctivitis was collected by a standard questionnaire developed by the American Thoracic Society. We used generalized non-linear and linear mixed models to test the associations. We observed linear exposure-response associations between O3 and all outcomes. The odds ratios of doctor-diagnosed asthma, rhinitis, eczema, and conjunctivitis associated with per interquartile increment in home-school O3 concentration were 1.31 (95 % confidence interval [CI]: 1.28, 1.34), 1.25 (95 %CI: 1.23, 1.28), 1.19 (95 %CI: 1.16, 1.21), and 1.28 (95 %CI: 1.21, 1.34), respectively. Similar associations were observed for asthma-related outcomes including current asthma, wheeze, current wheeze, persistent phlegm, and persistent cough. Moreover, stronger associations were observed among children who were aged > 12 years, physically inactive, and exposed to higher temperature. In conclusion, long-term O3 exposure was associated with higher risks of asthma, allergic rhinitis, conjunctivitis and eczema in children.
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Poluentes Atmosféricos , Asma , Cidades , Conjuntivite , Eczema , Ozônio , Rinite , Humanos , Ozônio/análise , Ozônio/toxicidade , Criança , China/epidemiologia , Asma/epidemiologia , Asma/induzido quimicamente , Eczema/epidemiologia , Eczema/induzido quimicamente , Masculino , Feminino , Rinite/epidemiologia , Rinite/induzido quimicamente , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Conjuntivite/induzido quimicamente , Conjuntivite/epidemiologia , Estudos Transversais , Exposição Ambiental/efeitos adversos , AdolescenteRESUMO
Background: Invasive fungal disease (IFD) has become a serious threat to human health in China and around the world, with high mortality and morbidity. Currently, the misdiagnosis rate of IFD is extremely high, compounded with the low quality of prescription antifungals and the high incidence of adverse events associated with IFD treatment, resulting in lengthy hospitalization, low clinical response, and high disease burden, which have become serious challenges in clinical practice. Antifungal stewardship (AFS) can not only significantly increase the early diagnosis rate of IFD, reduce inappropriate utilization of antifungal drugs, improve patient prognosis, but can also improve therapeutic safety and reduce healthcare expenses. Thus, it is urgent to identify key AFS metrics suitable for China's current situation. Methods: Based on metrics recommended by international AFS consensuses, combined with the current situation of China and the clinical experience of authoritative experts in various fields, several metrics were selected, and experts in the fields of respiratory diseases, hematology, intensive care units (ICUs), dermatology, infectious diseases, microbiology laboratory and pharmacy were invited to assess AFS metrics by the Delphi method. Consensus was considered to be reached with an agreement level of ≥80% for the metric. Results: Consensus was reached for 24 metrics, including right patient metrics (n=4), right time metrics (n=3), and right use metrics (n=17). Right use metrics were further subdivided into drug choice (n=8), drug dosage (n=4), drug de-escalation (n=1), drug duration (n=2), and drug consumption (n=2) metrics. Forty-six authoritative experts assessed and reviewed the above metrics, and a consensus was reached with a final agreement level of ≥80% for 22 metrics. Conclusions: This consensus is the first to propose a set of AFS metrics suitable for China, which helps to establish AFS standards in China and is also the first AFS consensus in Asia, and may improve the standard of clinical diagnosis and treatment of IFD, and guide hospitals to implement AFS, ultimately promoting the rational use of antifungal drugs and improving patient prognosis.
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BACKGROUND: Recent studies have demonstrated the relevance of circulating factors in the occurrence and development of colorectal cancer (CRC); however, the causal relationship remains unclear. METHODS: Summary-level data for CRC were obtained from the UK Biobank (5,657 cases and 372,016 controls), FinnGen cohort (3,022 cases and 215,770 controls), and BioBank Japan Project (BBJ, 7,062 cases and 195,745 controls). Thirty-two peripheral markers with consistent definitions were collected from the three biobanks. Mendelian randomization (MR) was used to evaluate the causal effect of circulating factors on CRC. The effects from the three consortiums were combined using trans-ancestry meta-analysis methods. RESULTS: Our analysis provided compelling evidence for the causal association of higher genetically predicted eosinophil cell count (EOS, odds ratio [OR], 0.8639; 95% confidence interval [CI] 0.7922-0.9421) and red cell distribution width (RDW, OR, 0.9981; 95% CI, 0.9972-0.9989) levels with a decreased risk of CRC. Additionally, we found suggestive evidence indicating that higher levels of total cholesterol (TC, OR, 1.0022; 95% CI, 1.0002-1.0042) may increase the risk of CRC. Conversely, higher levels of platelet count (PLT, OR, 0.9984; 95% CI, 0.9972-0.9996), total protein (TP, OR, 0.9445; 95% CI, 0.9037-0.9872), and C-reactive protein (CRP, OR, 0.9991; 95% CI, 0.9983-0.9999) may confer a protective effect against CRC. Moreover, we identified six ancestry-specific causal factors, indicating the necessity of considering patients' ancestry backgrounds before formulating prevention strategies. CONCLUSIONS: MR findings support the independent causal roles of circulating factors in CRC, which might provide a deeper insight into early detection of CRC and supply potential preventative strategies.
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Neoplasias Colorretais , Análise da Randomização Mendeliana , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/epidemiologia , Predisposição Genética para Doença , Masculino , Feminino , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Japão/epidemiologia , Fatores de RiscoRESUMO
Recent experimental and epidemiological studies underscore the vital interaction between the intestinal microbiota and the lungs, an interplay known as the "gut-lung axis". The significance of this axis has been further illuminated following the identification of intestinal microbial metabolites, such as short-chain fatty acids (SCFA), as key mediators in setting the tone of the immune system. Through the gut-lung axis, the gut microbiota and its metabolites, or allergens, are directly or indirectly involved in the immunomodulation of pulmonary diseases, thereby increasing susceptibility to allergic airway diseases such as asthma. Asthma is a complex outcome of the interplay between environmental factors and genetic predispositions. The concept of the gut-lung axis may offer new targets for the prevention and treatment of asthma. This review outlines the relationships between asthma and the respiratory microbiome, gut microbiome, and environmental microbiome. It also discusses the current advancements and applications of microbiomics, offering novel perspectives and strategies for the clinical management of chronic respiratory diseases like asthma.
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BACKGROUND: Patients with diabetes mellitus (DM) are vulnerable to community-acquired pneumonia (CAP), which have a high mortality rate. We aimed to investigate the value of heparin-binding protein (HBP) as a prognostic marker of mortality in patients with DM and CAP. METHODS: This retrospective study included CAP patients who were tested for HBP at intensive care unit (ICU) admission from January 2019 to April 2020. Patients were allocated to the DM or non-DM group and paired with propensity score matching. Baseline characteristics and clinical outcomes up to 90 days were evaluated. The primary outcome was the 10-day mortality. Receiver operating characteristic (ROC) curves, Kaplan-Meier analysis, and Cox regression were used for statistical analysis. RESULTS: Among 152 enrolled patients, 60 pairs were successfully matched. There was no significant difference in 10-day mortality, while more patients in the DM group died within 28 d (P=0.024) and 90 d (P=0.008). In the DM group, HBP levels at ICU admission were higher in 10-day non-survivors than in 10-day survivors (median 182.21 [IQR: 55.43-300] ng/ml vs. median 66.40 [IQR: 34.13-107.85] ng/mL, P=0.019), and HBP levels could predict the 10-day mortality with an area under the ROC curve of 0.747. The cut-off value, sensitivity, and specificity were 160.6 ng/mL, 66.7%, and 90.2%, respectively. Multivariate Cox regression analysis indicated that HBP was an independent prognostic factor for 10-day (HR 7.196, 95%CI: 1.596-32.455, P=0.01), 28-day (HR 4.381, 95%CI: 1.449-13.245, P=0.009), and 90-day mortality (HR 4.581, 95%CI: 1.637-12.819, P=0.004) in patients with DM. CONCLUSION: Plasma HBP at ICU admission was associated with the 10-day, 28-day, and 90-day mortality, and might be a prognostic factor in patients with DM and CAP.
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The upper respiratory tract is the initial site of SARS-CoV-2 infection. Nasal spike-specific secretory immunoglobulin A (sIgA) correlates with protection against Omicron breakthrough infection. We report that intranasal vaccination using human adenovirus serotype 5 (Ad5) vectored Omicron spike in people who previously vaccinated with ancestral vaccine could induce robust neutralizing sIgA in the nasal passage. Nasal sIgA was predominantly present in dimeric and multimeric forms and accounted for nearly 40% of total proteins in nasal mucosal lining fluids (NMLFs). A low-level IgG could also be detected in NMLFs but not IgM, IgD, and IgE. After a complete nasal wash, sIgA in the nasal passage could be replenished rapidly within a few hours. A comparison of purified paired serum IgA, serum IgG, and nasal sIgA from the same individuals showed that sIgA was up to 3-logs more potent than serum antibodies in binding to spikes and in neutralizing Omicron subvariants. Serum IgG and IgA failed to neutralize XBB and BA.2.86, while nasal sIgA retained potent neutralization against these newly emerged variants. Further analysis showed that sIgA was more effective than IgG or IgA in blocking spike-mediated cell-to-cell transmission and protecting hACE2 mice from XBB challenge. Using a sIgA monoclonal antibody as a reference, we estimated that the total nasal sIgA contains about 2.6-3.9% spike-specific sIgA in NMLFs collected approximately one month after intranasal vaccination. Our study provided insights for developing intranasal vaccines that can induce sIgA to build an effective and mutation-resistant first-line immune barrier against constantly emerging variants.
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Administração Intranasal , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , SARS-CoV-2/imunologia , SARS-CoV-2/genética , COVID-19/prevenção & controle , COVID-19/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Animais , Camundongos , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/genética , Vacinas contra COVID-19/administração & dosagem , Imunoglobulina A/imunologia , Imunoglobulina A/sangue , Imunoglobulina A/genética , Mucosa Nasal/imunologia , Mucosa Nasal/virologia , Feminino , Vetores Genéticos/imunologia , Vetores Genéticos/genética , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia , Imunoglobulina A Secretora/imunologia , Adenoviridae/genética , Adenoviridae/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , MasculinoRESUMO
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 , Sepse , Humanos , Sepse/mortalidade , Sepse/sangue , Sepse/diagnóstico , Masculino , Feminino , Biomarcadores/sangue , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Adulto , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Serum allergen-specific IgE (sIgE) detection is an important tool in the diagnosis of allergic diseases. However, the absence of international standards for sIgE detection systems raises questions about the comparability of different systems. OBJECTIVE: This study aims to evaluate three common allergen sIgE detection systems, with a primary focus on detecting dust mite allergens. METHODS: We recruited 85 children with rhinitis and 15 healthy control children. The subjects underwent testing with three different sIgE detection systems, including magnetic particle flow fluorescence, magnetic particle chemiluminescence, and protein chip, to detect sIgE levels to HDM extracts. In addition, skin prick testing (SPT) was conducted, and protein chip technology was performed to measure sIgE levels to component proteins. RESULTS: Our findings reveal strong consistency between SPT and the three in vitro detection systems, with consistency exceeding 71.76% for dust mite allergens. Moreover, there was excellent consistency and RAST class consistency among the three in vitro detection systems, with scores exceeding 94.12% and 89.00%, respectively. And for the 13 additional allergens crude extracts sIgE simultaneously detected by systems 1 and 2, the results showed that the consistency of both systems was above 87.00%, and the RAST class consistency was above 82.00%. CONCLUSION: The three serum sIgE detection systems exhibited an approximate 80% concordance rate with SPT in identifying dust mite allergens. Furthermore, these systems demonstrated excellent consistency and RAST class consistency among themselves. These findings suggest that the three assays introduced in this study are interchangeable in allergen diagnosis.
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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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Artrite Reumatoide , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Análise da Randomização Mendeliana , Miosinas/genética , Perfilação da Expressão Gênica , Transcriptoma , Locos de Características Quantitativas , Prognóstico , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , MultiômicaRESUMO
BACKGROUND: Monocyte-derived alveolar macrophages (Mo_AMs) are increasingly recognised as potential pathogenic factors for idiopathic pulmonary fibrosis (IPF). While scRNAseq analysis has proven valuable in the transcriptome profiling of Mo_AMs, the integration analysis of multi-omics may provide additional dimensions of understanding of these cellular populations. METHODS: We performed multi-omics analysis on 116 scRNAseq, 119 bulkseq and five scATACseq lung tissue samples from IPF. We built a large-scale IPF scRNAseq atlas and conducted the Monocle 2/3 as well as the Cellchat to explore the developmental path and intercellular communication on Mo_AMs. We also reported the difference in metabolisms, tissue repair and phagocytosis between Mo_AMs and tissue-resident alveolar macrophages (TRMs). To determine whether Mo_AMs affected pulmonary function, we projected clinical phenotypes (FVC%pred) from the bulkseq dataset onto the scRNAseq atlas. Finally, we used scATATCseq to uncover the upstream regulatory mechanisms and determine key drivers in Mo_AMs. RESULTS: We identified three Mo_AMs clusters and the trajectory analysis further validated the origin of these clusters. Moreover, via the Cellchat analysis, the CXCL12/CXCR4 axis was found to be involved in the molecular basis of reciprocal interactions between Mo_AMs and fibroblasts through the activation of the ERK pathway in Mo_AMs. SPP1_RecMacs (RecMacs, recruited macrophages) were higher in the low-FVC group than in the high-FVC group. Specifically, compared with TRMs, the functions of lipid and energetic metabolism as well as tissue repair were higher in Mo_AMs than TRMs. But, TRMs may have higher level of phagocytosis than TRMs. SPIB (PU.1), JUNB, JUND, BACH2, FOSL2, and SMARCC1 showed stronger association with open chromatin of Mo_AMs than TRMs. Significant upregulated expression and deep chromatin accessibility of APOE were observed in both SPP1_RecMacs and TRMs. CONCLUSION: Through trajectory analysis, it was confirmed that SPP1_RecMacs derived from Monocytes. Besides, Mo_AMs may influence FVC% pred and aggravate pulmonary fibrosis through the communication with fibroblasts. Furthermore, distinctive transcriptional regulators between Mo_AMs and TRMs implied that they may depend on different upstream regulatory mechanisms. Overall, this work provides a global overview of how Mo_AMs govern IPF and also helps determine better approaches and intervention therapies.
Assuntos
Fibrose Pulmonar Idiopática , Macrófagos Alveolares , Monócitos , Humanos , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/genética , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Monócitos/metabolismo , Masculino , Perfilação da Expressão Gênica , Feminino , Receptores CXCR4/metabolismo , Receptores CXCR4/genética , Pessoa de Meia-Idade , Fenótipo , Pulmão/patologia , Pulmão/metabolismo , Regulação da Expressão GênicaRESUMO
Introduction: Infection with SARS-CoV-2 begins in the upper respiratory tract and can trigger the production of mucosal spike-specific secretory IgA (sIgA), which provides protection against reinfection. It has been recognized that individuals with high level of nasal spike-specific IgA have a lower risk of reinfection. However, mucosal spike-specific sIgA wanes over time, and different individuals may have various level of spike-specific sIgA and descending kinetics, leading to individual differences in susceptibility to reinfection. A method for detecting spike-specific sIgA in the nasal passage would be valuable for predicting the risk of reinfection so that people at risk can have better preparedness. Methods: In this study, we describe the development of a colloidal gold-based immunochromatographic (ICT) strip for detecting SARS-CoV-2 Omicron spike-specific sIgA in nasal mucosal lining fluids (NMLFs). Results: The ICT strip was designed to detect 0.125 µg or more spike-specific sIgA in 80 µL of NMLFs collected using a nasal swab. Purified nasal sIgA samples from individuals who recently recovered from an Omicron BA.5 infection were used to demonstrate that this ICT strip can specifically detect spike-specific sIgA. The signal levels positively correlated with neutralizing activities against XBB. Subsequent analysis revealed that people with low or undetectable levels of spike-specific sIgA in the nasal passage were more susceptible to SARS-CoV-2 reinfection. Conclusions: This nasal spike-specific sIgA ICT strip provides a non-invasive, rapid, and convenient method to assess the risk of reinfection for achieving precision preparedness.
RESUMO
Near-infrared (NIR) hyperspectral imaging is a powerful technique that enables the capture of three-dimensional (3D) spectra-spatial information within the NIR spectral range, offering a wide array of applications. However, the high cost associated with InGaAs focal plane array (FPA) has impeded the widespread adoption of NIR hyperspectral imaging. Addressing this challenge, in this study, we adopt an alternative approach-single-pixel detection for NIR hyperspectral imaging. Our investigation reveals that single-pixel detection outperforms conventional FPA, delivering a superior signal-to-noise ratio (SNR) for both spectral and imaging reconstruction. To implement this strategy, we leverage self-assembled colloidal quantum dots (CQDs) and a digital micromirror device (DMD) for NIR spectral and spatial information multiplexing, complemented by single-pixel detection for simultaneous spectral and image reconstruction. Our experimental results demonstrate successful NIR hyperspectral imaging with a detection window about 600 nm and an average spectral resolution of 8.6 nm with a pixel resolution of 128 × 128. The resulting spectral and spatial data align well with reference instruments, which validates the effectiveness of our approach. By circumventing the need for expensive and bulky FPA and wavelength selection components, our solution shows promise in advancing affordable and accessible NIR hyperspectral imaging technologies, thereby expanding the range of potential applications.
RESUMO
Fine particulate matter (PM2.5) has been extensively implicated in the pathogenesis of neurodevelopmental disorders, but the underlying mechanism remains unclear. Recent studies have revealed that PM2.5 plays a role in regulating iron metabolism and redox homeostasis in the brain, which is closely associated with ferroptosis. In this study, the role and underlying mechanism of ferroptosis in PM2.5-induced neurotoxicity were investigated in mice, primary hippocampal neurons, and HT22 cells. Our findings demonstrated that exposure to PM2.5 could induce abnormal behaviors, neuroinflammation, and neuronal loss in the hippocampus of mice. These effects may be attributed to ferroptosis induced by PM2.5 exposure in hippocampal neurons. RNA-seq analysis revealed that the upregulation of iron metabolism-related protein Heme Oxygenase 1 (HO-1) and the activation of mitophagy might play key roles in PM2.5-induced ferroptosis in HT22 cells. Subsequent in vitro experiments showed that PM2.5 exposure significantly upregulated HO-1 in primary hippocampal neurons and HT22 cells. Moreover, PM2.5 exposure activated mitophagy in HT22 cells, leading to the loss of mitochondrial membrane potential, alterations in the expression of autophagy-related proteins LC3, P62, and mTOR, as well as an increase in mitophagy-related protein PINK1 and PARKIN. As a heme-degradation enzyme, the upregulation of HO-1 promotes the release of excess iron, genetically inhibiting the upregulation of HO-1 in HT22 cells could prevent both PM2.5-induced mitophagy and ferroptosis. Furthermore, pharmacological inhibition of mitophagy in HT22 cells reduced levels of ferrous ions and lipid peroxides, thereby preventing ferroptosis. Collectively, this study demonstrates that HO-1 mediates PM2.5-induced mitophagy-dependent ferroptosis in hippocampal neurons, and inhibiting mitophagy or ferroptosis may be a key therapeutic target to ameliorate neurotoxicity following PM2.5 exposure.