RESUMO
Macrophage activation syndrome (MAS) is a potentially fatal consequence of adult-onset Still's disease (AOSD), driven by a cytokine storm. Efficient early diagnosis of AOSD-associated MAS requires a sensitive and specific biomarker. In this study, we demonstrated that pentraxin 3 (PTX3), an acute phase protein, was associated with AOSD disease activity and served as a biomarker for AOSD-MAS. PTX3 levels were significantly increased in AOSD patients compared to other autoimmune diseases and healthy controls. Plasma PTX3 levels showed positive correlations with inflammatory markers, the systemic score and the HScore. In active AOSD with MAS, PTX3 levels were higher compared to those in non-AOSD haemophagocytic lymphohistiocytosis (HLH) patients. Moreover, the PTX3's area under the curve value for distinguishing AOSD with MAS exceeded that of soluble interleukin-2 receptor, ferritin and C-reactive protein. Furthermore, plasma levels of PTX3 were associated with circulating NET-DNA levels. To fully understand the underlying mechanism of PTX3 prompting AOSD and AOSD-MAS progression, we discovered that neutrophils exhibited enhanced NET formation and mitogen-activated protein kinases (MAPK) pathway activation upon PTX3 stimulation. More importantly, PTX3-induced NET formation was effectively dampened by MAPK pathway inhibitors. These findings collectively revealed that PTX3 has a favorable correlation with disease activity and may serve as a potential biomarker to differentiate AOSD patients with MAS. Additionally, PTX3 induces NET release via the MAPK pathway, suggesting a pathogenic role in AOSD-MAS.
Assuntos
Síndrome de Ativação Macrofágica , Componente Amiloide P Sérico , Doença de Still de Início Tardio , Adulto , Humanos , Biomarcadores , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Síndrome de Ativação Macrofágica/diagnóstico , Ativação de Neutrófilo , Componente Amiloide P Sérico/metabolismo , Doença de Still de Início Tardio/sangue , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/imunologiaRESUMO
BACKGROUND: Complex interactions between the immune system and the brain may affect neural development, survival, and function, with etiological and therapeutic implications for neurodegenerative diseases. However, previous studies investigating the association between immune inflammation and Alzheimer's disease (AD) have yielded inconsistent results. METHODS: We applied Mendelian randomization (MR) to examine the causal relationship between immune cell traits and AD risk using genetic variants as instrumental variables. MR is an epidemiological study design based on genetic information that reduces the effects of confounding and reverse causation. We analyzed the causal associations between 731 immune cell traits and AD risk based on publicly available genetic data. RESULTS: We observed that 5 immune cell traits conferred protection against AD, while 7 immune cell traits increased the risk of AD. These immune cell traits mainly involved T cell regulation, monocyte activation and B cell differentiation. Our findings suggest that immune regulation may influence the development of AD and provide new insights into potential targets for AD prevention and treatment. We also conducted various sensitivity analyses to test the validity and robustness of our results, which revealed no evidence of pleiotropy or heterogeneity. CONCLUSION: Our research shows that immune regulation is important for AD and provides new information on potential targets for AD prevention and treatment. However, this study has limitations, including the possibility of reverse causality, lack of validation in independent cohorts, and potential confounding by population stratification. Further research is needed to validate and amplify these results and to elucidate the potential mechanisms of the immune cell-AD association.
Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/genética , Análise da Randomização Mendeliana , Encéfalo , Causalidade , Inflamação , Estudo de Associação Genômica AmplaRESUMO
BACKGROUND: Myopia is the most prevalent refractive error and a growing global health concern that significantly affects visual function. Researchers have recently emphasized considerably on the influence of lifestyle on myopia incidence and development. This study investigates the relationship between leisure sedentary behaviors (LSB)/physical activity (PA)/sleep traits and myopia. METHODS: LSB, PA, and sleep trait-associated genetic variants were used as instrument variables in a Mendelian randomization (MR) study to examine their causal effects on myopia. Summary genome-wide association studies (GWASs) statistical data for LSB and PA were obtained from UK Biobank, and the data of sleep traits was obtained from UK Biobank, UK Biobank and 23andMe, and FinnGen. We used summary statistics data for myopia from MRC IEU. The MR analyses was performed using the inverse variance-weighted (IVW), MR-Egger, weighted median, and MR Pleiotropy RESidual Sum and Outlier methods. RESULTS: Computer use was genetically predicted to increase the myopia risk [IVW odds ratio (OR) = 1.057; 95% confidence interval (CI), 1.038-1.078; P = 7.04 × 10- 9]. The self-reported moderate-to-vigorous physical activity (MVPA) (IVW OR = 0.962; 95% CI, 0.932-0.993; P = 1.57 × 10- 2) and television watching (IVW OR = 0.973; 95% CI, 0.961-0.985, P = 1.93 × 10- 5) were significantly associated with a lower myopia risk. However, genetically predicted sleep traits or accelerometer-measured physical activity had no significant associations with myopia. CONCLUSION: Our results indicated that computer use is a risk factor for myopia, whereas television watching and MVPA may protect against myopia. These findings shed new light on possible strategies for reducing the prevalence of myopia.
Assuntos
Miopia , Comportamento Sedentário , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Miopia/epidemiologia , Miopia/genética , Exercício Físico , Sono , Atividades de LazerRESUMO
OBJECTIVE: Post-stroke dysphagia is a common swallowing disorder that occurs after a stroke, leading to an increased risk of aspiration pneumonia and malnutrition. There is a pressing need for effective and safe interventions for its rehabilitation. This review aims to answer two key scientific questions: (1) What is the efficacy of repetitive transcranial magnetic stimulation in the rehabilitation of post-stroke dysphagia? (2) Is repetitive transcranial magnetic stimulation a safe intervention for post-stroke dysphagia? DATA SOURCES: A comprehensive search was conducted across four electronic databases: PubMed, Cochrane Library, Web of Science, and Embase. The search aimed to identify relevant studies concerning our topic of interest and was completed on 28 May 2024. REVIEW METHODS: In accordance with the PRISMA checklist, a comprehensive search of four databases was conducted, which identified 13 relevant systematic reviews. The inclusion criteria were systematic reviews that evaluated the efficacy and safety of repetitive transcranial magnetic stimulation for post-stroke dysphagia. Exclusion criteria were reviews that did not focus on post-stroke dysphagia or did not evaluate repetitive transcranial magnetic stimulation as a therapeutic intervention. The quality, bias, reporting, and overall evidence quality of these reviews were assessed using validated tools, including the AMSTAR 2 tool for assessing the methodological quality of systematic reviews, the ROBIS tool for assessing the risk of bias, and the GRADE approach for evaluating the overall quality of evidence. This rigorous approach ensures that our review provides a comprehensive and reliable overview of the current state of knowledge on the use of repetitive transcranial magnetic stimulation for post-stroke dysphagia. RESULTS: The sample sizes for the individual studies included in the systematic reviews/meta-analyses ranged from 66 to 555. The total number of participants across all studies included in the overall analyses was 752. The evidence was limited by the methodological flaws and heterogeneity of the systematic reviews. The quality of the evidence varied from high to low, with most outcomes having moderate quality. Future research should adopt more rigorous, standardized, and comprehensive designs to confirm the efficacy and safety of repetitive transcranial magnetic stimulation for post-stroke dysphagia. The main reason for downgrading the evidence quality was the small sample size and high heterogeneity of the primary studies. CONCLUSION: This overview synthesized research on repetitive transcranial magnetic stimulation for dysphagia, aiming to inform clinical and policy decisions. However, the current evidence does not conclusively establish the safety and efficacy of repetitive transcranial magnetic stimulation for post-stroke dysphagia rehabilitation. The studies reviewed varied in quality, and many were of poor quality. Therefore, while some studies suggest potential benefits of repetitive transcranial magnetic stimulation, these findings should be interpreted with caution. There is a pressing need for more rigorous, high-quality research to validate the use of repetitive transcranial magnetic stimulation for post-stroke dysphagia rehabilitation. The implications of these findings for clinical practice and policy will be clearer once we have more robust, evidence-based recommendations.
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This study aimed to investigate the causal relationship between inflammatory cytokines and the risk of varicose veins. The data were sourced from genome-wide association studies (GWAS) of European individuals. Multiple Mendelian randomization (MR) methods were used to evaluate the association between inflammatory cytokines and varicose veins. The study found significant associations between elevated levels of certain inflammatory biomarkers (e.g., CASP-8, Vascular endothelial growth factor A levels (VEGF_A)) and an increased risk of varicose veins, while others (e.g., 4EBP1, MMP-10) showed a protective effect. The MR-Egger Intercept and heterogeneity tests indicated no significant pleiotropy or heterogeneity. This comprehensive MR analysis identifies several cytokines as potential contributors to the pathogenesis of varicose veins, offering insights into novel therapeutic targets. Our findings underscore the importance of inflammation in varicose veins and suggest that targeting specific cytokines could be a promising strategy for the treatment and prevention of varicose veins.
Assuntos
Estudo de Associação Genômica Ampla , Varizes , Humanos , Análise da Randomização Mendeliana , Fator A de Crescimento do Endotélio Vascular , Varizes/genética , Citocinas/genéticaRESUMO
BACKGROUND: Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disease characterized by innate immune system activation, with a high risk for macrophage activation syndrome (MAS). MAS development is associated with monocyte/macrophage activation and cytokine storm. Monocytes consist of three different subsets, classical monocytes (CMs, CD14brightCD16 -), intermediate monocytes (IMs, CD14brightCD16 +), and non-classical monocytes (NCMs, CD14dimCD16 +), each has distinct roles in inflammatory regulation. However, the frequencies and regulatory mechanism of monocyte subsets in AOSD patients have not been identified. METHODS: We performed flow cytometry, RNA sequencing, phagocytosis analysis, and enzyme-linked immunosorbent assay to evaluate monocyte subsets, cell functions, and potential biomarkers. The effect of neutrophil extracellular traps (NETs) on monocytes was determined by evaluating mRNA levels of DNA sensors, surface CD16 expression, and inflammasome pathway activation. RESULTS: Higher proportions of intermediate monocytes (IMs) were identified in active AOSD patients. IMs displayed higher expression of CD80, CD86, HLA-DR, and CD163 than CMs and NCMs. CD163 upregulation was noted on AOSD IMs, accompanied by increased phagocytic activity and elevated cytokine/chemokine production, including IL-1ß, IL-6, CCL8, and CXCL10. The frequencies of IMs were correlated with disease activity and higher in AOSD patients with MAS (AOSD-MAS). CCL8 and CXCL10 were highly expressed in RNA sequencing of monocytes from AOSD-MAS patients and plasma CXCL10 level could serve as a potential biomarker for AOSD-MAS. Moreover, DNA-sensing pathway was activated in monocytes from AOSD-MAS patients. Stimulation with NETs derived from AOSD induced DNA sensor expression, the expansion of IMs, and inflammasome pathway activation. These effects can be abrogated by DNase I treatment. CONCLUSIONS: Our results demonstrated that the proportions of IMs were elevated in AOSD and associated with MAS. The DNA component in NETs from AOSD plays an important role in the formation of IMs, shedding new light for the therapeutic target.
Assuntos
Armadilhas Extracelulares , Síndrome de Ativação Macrofágica , Doença de Still de Início Tardio , Adulto , Humanos , Doença de Still de Início Tardio/complicações , Doença de Still de Início Tardio/tratamento farmacológico , Monócitos/metabolismo , Armadilhas Extracelulares/metabolismo , Síndrome de Ativação Macrofágica/complicações , Inflamassomos/metabolismo , Biomarcadores , DNA/metabolismo , DNA/uso terapêuticoRESUMO
DNA methylation plays an important role in gene regulation and genomic stability. However, large DNA hypomethylated regions known as DNA methylation valleys (DMVs) or canyons have also been suggested to serve unique regulatory functions, largely unknown in rice (Oryza sativa). Here, we describe the DMVs in rice seedlings, which were highly enriched with developmental and transcription regulatory genes. Further detailed analysis indicated that grand DMVs (gDMVs) might be derived from nuclear integrants of organelle DNA (NORGs). Furthermore, Domains Rearranged Methylase 2 (OsDRM2) maintained DNA methylation at short DMV (sDMV) shores. Epigenetic maps indicated that sDMVs were marked with H3K4me3 and/or H3K27me3, although the loss of DNA methylation had a negligible effect on histone modification within these regions. In addition, we constructed H3K27me3-associated interaction maps for homozygous T-DNA insertion mutant of the gene (osdrm2) and wild type (WT). From a global perspective, most (90%) compartments were stable between osdrm2 and WT plants. At a high resolution, we observed a dramatic loss of long-range chromatin loops in osdrm2, which suffered an extensive loss of non-CG (CHG and CHH, H = A, T, or C) methylation. From another viewpoint, the loss of non-CG methylation at sDMV shores in osdrm2 could disrupt H3K27me3-mediated chromatin interaction networks. Overall, our results demonstrated that DMVs are a key genomic feature in rice and are precisely regulated by epigenetic modifications, including DNA methylation and histone modifications. OsDRM2 maintained DNA methylation at sDMV shores, while OsDRM2 deficiency strongly affected three-dimensional (3D) genome architectures.
Assuntos
Metilação de DNA , Oryza , Metilação de DNA/genética , Cromatina/genética , Histonas/genética , Histonas/metabolismo , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Metiltransferases/genética , DNA , Regulação da Expressão Gênica de Plantas/genéticaRESUMO
OBJECTIVE: A succession of cases have reported flares of adult-onset Still's disease (AOSD) after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising concerns. We aimed to investigate the impact of inactivated SARS-CoV-2 vaccines on disease activity in patients with AOSD. METHODS: We prospectively enrolled clinically inactive AOSD patients visiting the outpatient clinics of our department. The patients received SARS-CoV-2 vaccines (BBIBP-CorV, Sinopharm, Beijing, China) voluntarily. The occurrence of relapse in the participants was recorded during the follow-up period, and a propensity score matching (PSM) method was used to compare the relapse rates between vaccinated and unvaccinated patients. Localized and systemic symptoms were assessed in the vaccinated patients. RESULTS: A total of 122 patients with inactive AOSD were included, of which 49.2% (n = 60) voluntarily received the inactivated SARS-CoV-2 vaccine. The relapse rate did not increase significantly in vaccinated patients in comparison with unvaccinated patients (after PSM: 6.8% vs 6.8%), and no relapse occurred within 1 month after vaccination. No obvious adverse reactions were reported in 75.0% of the participants, and none of the patients reported severe reactions. CONCLUSION: Increased disease activity or relapse following vaccination with inactivated SARS-CoV-2 was rare in patients with inactive AOSD. Local and systemic adverse reactions were found to be mild and self-limiting. These safety profiles of inactivated SARS-CoV-2 vaccines in patients with AOSD may assist in eliminating vaccine hesitancy and increase the vaccination rate against SARS-CoV-2.
Assuntos
COVID-19 , Doença de Still de Início Tardio , Adulto , Humanos , Vacinas contra COVID-19/efeitos adversos , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Doença de Still de Início Tardio/diagnósticoRESUMO
OBJECTIVE: To explore whether inactivated coronavirus disease 2019 vaccine influences the profile of prothrombotic autoantibodies and induces thrombotic events in primary APS patients. METHODS: We enrolled 39 primary APS patients who received two doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (BBIBPCorV, Sinopharm, Beijing, China) voluntarily in this prospective cohort. Prothrombotic autoantibodies were determined before vaccination and 4 weeks after the second dose of vaccination. Thrombotic disorders were evaluated via hospital site visits and assessments. RESULTS: There was no significant difference in the presence of all 11 autoantibodies detected before and 4 weeks after vaccination: for aCL, IgG (14 vs 16, P = 0.64), IgM (13 vs 19, P = 0.34), IgA (2 vs 3, P = 0.64); anti-ß2GP1, IgG (12 vs 12, P = 1.00), IgM (5 vs 8, P = 0.36), IgA (4 vs 3, P = 0.69); anti-PS/PT IgG (13 vs 16, P = 0.48), IgM (17 vs 22, P = 0.26); LAC (22 vs 28, P = 0.16); aPF4-heparin (0 vs 0, P = 1.00) and ANA (23 vs 26, P = 0.48). Notably, the distribution of the aPL profile in the pre- and post-vaccination cohorts was not affected by SARS-CoV-2 vaccination: for patients with a low-risk aPL profile (11 vs 10, P = 0.799) and patients with a high-risk aPL profile (28 vs 29, P = 0.799), respectively. Furthermore, no case exhibited symptoms of the thrombotic disorder during a minimum follow-up period of 12 weeks. There was no adjustment to the ongoing treatment regimens following SARS-CoV-2 vaccination. CONCLUSION: Inactivated SARS-CoV-2 vaccine does not influence the profile of anti-phospholipid antibodies and anti-PF4-heparin antibodies nor induces thrombotic events in primary APS patients.
Assuntos
Síndrome Antifosfolipídica , COVID-19 , Trombose , Humanos , Vacinas contra COVID-19 , Estudos Prospectivos , COVID-19/prevenção & controle , SARS-CoV-2 , Trombose/etiologia , Autoanticorpos , Imunoglobulina G , Imunoglobulina M , Imunoglobulina A , HeparinaRESUMO
OBJECTIVE: Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disorder. The understanding of the changes in adaptive immune cells and the crosstalk between innate and adaptive immune systems in AOSD is limited. This study aimed to examine the peripheral immune cell composition and inflammatory protein levels in AOSD patients. METHODS: Twenty-nine active AOSD patients were enrolled. Flow cytometry was used to analyze the cell populations in peripheral blood. Antibody chips were utilized to detect the protein expression profile in serum. RESULTS: In active AOSD patients, there was an increase in the percentage of classical and non-classical monocytes among peripheral blood mononuclear cells. The proportion of natural killer (NK) cells decreased, with an increase in CD56dim NK1 cells and a decrease in CD56bright NK2 cells compared with healthy controls (HC). The percentage of naïve central memory T cells was decreased, while the percentage of effector and effector memory T cells was increased among adaptive lymphocytes. The proportion of naïve B and memory B cells was decreased, while plasma cells were increased in AOSD patients, indicating activation of the adaptive immune system. Additionally, the serum levels of 40 proteins were elevated in AOSD patients, primarily involved in cytokine-cytokine receptor interaction, inflammatory response, and regulation of MAPK cascade. CONCLUSION: Our findings showed the activation of the innate and adaptive immune system in AOSD. The protein-protein interaction analysis suggested potential communication between innate and adaptive cell subsets. These findings provide new insights into the pathogenesis of the disease and the development of targeted therapies.
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Halogenated methanesulfonic acids (HMSAs) are an important new class of organic compounds as they were universal in the water cycle and drinking water sources. However, no study has investigated the presence of HMSAs in surface water and sediment from China. The present study reports the occurrence and spatiotemporal distribution of seven HMSAs in water and sediment samples from Hangzhou Bay, China. Trifluoromethanesulfonic acid (TFMSA) was the main contributor to the concentrations of HMSAs in water and sediment samples from spring, summer, autumn and winter which were 30.8-541 ng/L, n. d.-86.6 ng/L, 4.22-70.9 ng/L and 8.86-192 ng/L, separately, while in sediment samples were n. d.-11.1 ng/g, n. d.-12.9 ng/g, n. d.-22.5 ng/g, n. d.-4.60 ng/g, respectively. The levels of HMSAs in water from winter and spring were higher than those in summer and autumn, and the concentrations of the target HMSAs in water presents a seasonal pattern affected by the temperature, the precipitation and river flow variations. Nevertheless, the levels of HMSAs in sediment were highest in the area near the industrial area and the confluences of rivers. Correlation analysis revealed that the concentrations of TFMSA were significantly positively correlated with total organic carbon (TOC) in water samples. Although TFMSA is regarded as low toxic based on the EC50 value of acute toxicity, the potential risks to aquatic ecology should be paid more attention due to its high concentrations in the aquatic system and the environmental persistency.
Assuntos
Água Potável , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Baías , Monitoramento Ambiental , Água Potável/análise , China , Rios , Sedimentos Geológicos/análiseRESUMO
Adult-onset Still's disease (AOSD) is a rare but clinically well-known auto-inflammatory disorder. Cytokine storm, the hallmark of AOSD, is mediated by neutrophil hyperactivation and enhanced neutrophil extracellular trap (NET) formation. Type I interferons (IFNs), having a primary role in the initiation of proinflammation responses, can induce subsequent inflammatory cytokine production. However, the role of type I IFNs in AOSD is unclear. Indeed, high levels of IFN-α and IFN-ß expression are presented by AOSD patients. In this investigation, hierarchical unsupervised clustering was performed on IFN-α and IFN-ß data to identify a cluster of AOSD patients who had a serious condition. Neutrophils from treatment-naïve active AOSD patients showed very strong enrichment in their IFN-α response, as shown by RNA-seq and confirmed by the IFN score. Whether IFN-α stimulates NET formation was also tested. IFN-α had the ability to form NETs that contained oxidized mitochondrial DNA (ox-mtDNA). Moreover, the JAK inhibitor could be used to dampen type I IFN-induced NET formation and eventually control ox-mtDNA release. Our results demonstrated the important roles of type I IFNs in the pathogenesis of AOSD through their promotion of NET formation, as characterized by the enhanced level of ox-mtDNA. The findings open up new avenues of research into therapeutic approaches for AOSD.
Assuntos
Armadilhas Extracelulares , Interferon Tipo I , Doença de Still de Início Tardio , Adulto , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Armadilhas Extracelulares/metabolismo , Humanos , Interferon Tipo I/metabolismo , Neutrófilos/metabolismo , Doença de Still de Início Tardio/tratamento farmacológicoRESUMO
Developing multifunctional hydrogels with stretchability, self-healing ability, adhesiveness, and conductivity into flexible strain sensors for human motion and health monitoring has attracted great attention and is highly desired. However, the present motion detectors mainly focus on stretching, bending, and twisting of different body parts while the expansion-contraction motion has been rarely investigated. In this study, along with carbon nanotubes (CNTs) as conductive components, sodium alginate (Alg) modified with 3-aminophenylboronic acid (PBA) and dopamine (DA) were synthesized and employed as precursors to prepare a multifunctional Alg-CNT hydrogel. The formed dynamic covalent bonds between PBA and DA endowed the hydrogel with a rapid self-healing property (30 s) while the introduction of CNTs remarkably enhanced the mechanical strength and electrical conductivity of the hydrogel. Moreover, the as-prepared hydrogel displayed a satisfactory stretchability (500%) and self-adhesiveness to various substrates. When used as a strain sensor, the Alg-CNT hydrogel that exhibited a fast response (150 ms) and ultra-durability (over 30 000 cycles) was demonstrated to be capable of monitoring subtle expansion-contraction motions (e.g., human breathing and mouse heart beating) via periodic and repeatable electrical signals. Therefore, this multifunctional hydrogel is highly suitable for monitoring expansion-contraction motions, indicating its potential applications in personal health monitoring.
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Nanotubos de Carbono , Dispositivos Eletrônicos Vestíveis , Adesivos , Alginatos , Animais , Condutividade Elétrica , Hidrogéis/química , Camundongos , Nanotubos de Carbono/químicaRESUMO
Making a hydrogel-based first-aid bandage with green resources, desirable biocompatibility, universal adhesive properties, low cost and simple production is a long-standing research aspiration. Considering this, three naturally existing organic acids, namely tannic acid, thioctic acid and phytic acid, were used to construct a novel adhesive gel (TATAPA hydrogel) for epidermal tissue bandage applications. This hydrogel could be synthesized under mild conditions with no need for a freeze-thawing shaping procedure, and was transparent, moldable and stretchable with good stability under continuous water immersion. In lap-shear tests, the TATAPA hydrogel could adhere to various hydrophilic and hydrophobic surfaces. Moreover, in the case of skin tissue adhesion, the hydrogel could be easily peeled off from the skin, meeting wearability requirements. Rheological tests showed that the hydrogel possessed thermal sensitive properties derived from multi-supramolecular interactions. The methicillin-resistant Staphylococcus aureus (MRSA)-infected burn wound test demonstrated that the hydrogel had desirable antibacterial activity and was beneficial for wound healing. A femoral artery bleeding assay was also used to reveal that the TATAPA hydrogel could be directly pasted onto the bleeding site for hemostasis. Overall, this hydrogel demonstrates potential as a surgical bioadhesive for a broad range of medical applications.
Assuntos
Bandagens , Hidrogéis , Staphylococcus aureus Resistente à Meticilina , Adesivos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Hidrogéis/química , Ácido Fítico , Taninos , Ácido TiócticoRESUMO
Time in range (TIR) is a novel indicator of glycaemic control that has been reported to have an association with diabetic complications. The objective of the study was to explore the association of TIR with postoperative wound healing in patients with diabetic foot ulcers (DFUs). We retrospectively analysed the data of DFU patients who had undergone surgical treatment from 2015 to 2019. A 1:1 ratio in propensity score matching (PSM) was adopted to compare patients with TIR ≥50% with those <50%. Data were summarised using chi-squared, Fisher's exact, and Mann-Whitney U tests. Patients with TIR <50% underwent a higher rate of secondary surgery within a month (P = .032) and had a longer hospital stay (P = .045) with greater hospital charges (P < .001) than the TIR ≥50% group. Multivariate analysis revealed that TIR (P = .034), Wagner score (P = .009), diabetes treatment (P = .006), and type of surgery (P = .013) were independent risk factors for secondary surgery. Additionally, patient subgroups with TIR <50% and baseline HbA1c < 7.5% (P = .025), albumin level ≥ 30 g/L (P = .039), HDL < 1.16 (P = .021), or Wagner score ≥ 3 (P = .048) also experienced a higher incidence of secondary surgery. TIR was correlated with postoperative wound healing in patients with DFUs. Strict glycaemic targets should be established for surgical patients.
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Diabetes Mellitus , Pé Diabético , Albuminas , Pé Diabético/etiologia , Hemoglobinas Glicadas , Humanos , Estudos Retrospectivos , CicatrizaçãoRESUMO
Adult-onset Still's disease (AOSD) is a rare, but characteristic non-familial, multi-genic systemic auto-inflammatory disorder, characterized by high spiking fever, salmon-like evanescent skin rash, polyarthritis, sore throat, hyperferritinemia and leucocytosis. The hallmark of AOSD is a cytokine storm triggered by dysregulation of inflammation. Nowadays, with advances in anti-cytokine biologic agents, the treatment of AOSD is no longer limited to NSAIDs, glucocorticoids or conventional synthetic DMARDs. In this review, we focussed on the roles of these cytokines in the pathogenesis of AOSD and summarized the current and emerging biological therapy.
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Terapia Biológica/métodos , Doença de Still de Início Tardio/terapia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/terapia , Humanos , Doença de Still de Início Tardio/imunologiaRESUMO
OBJECTIVES: To describe the detailed characteristics and explore the potential risk factors of relapses in patients with adult-onset Still's disease (AOSD). METHODS: We enrolled patients with AOSD admitted to the Department of Rheumatology and Immunology, Ruijin Hospital from August 2016 to September 2019. Kaplan-Meier curves and the log rank test were used to estimate the cumulative relapse probability and persistent remission rate before the first occurrence of relapse. The multivariate Cox proportional hazard method was utilized to identify risk factors associated with relapses of AOSD. RESULTS: A total of 122 patients with AOSD were enrolled with a median follow-up of 12.6 months. Among them, 26 (21.3%) patients had at least one relapse. The cumulative relapse rates of AOSD patients were 14.42%, 21.79%, 24.81% and 28.57% at 6, 12, 18 and 36 months, respectively. According to the multivariate analysis, intensive treatment (odds ratio: 6.848; 95% CI: 2.441, 19.211) and macrophage activation syndrome (odds ratio: 4.020, 95% CI: 1.564, 10.322) were associated with increased risk of relapse. CONCLUSION: Our study indicated that relapses occurred in at least one-fifth of patients with AOSD, and patients with high disease severity at initial attack may have an increased risk of relapse, which needs more intensive therapy and close follow-up.
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Índice de Gravidade de Doença , Doença de Still de Início Tardio/patologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recidiva , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: Liver damage is a common manifestation and can be life-threatening in adult-onset Still's disease (AOSD), an autoinflammatory disease. The hallmark of AOSD is activation of neutrophils, whose infiltration in liver is suspected to promote tissue injury. Here we aimed to identify a candidate biomarker and to validate its association with liver damage in AOSD. METHODS: Transcriptome analysis of neutrophils from treatment-naïve active AOSD patients and healthy donors was performed. Lipocalin-2 (LCN2) expression was assessed in neutrophils, plasma and liver biopsies of AOSD. The correlations of LCN2 with different variables and its ability to identify liver damage from AOSD patients were analysed. RESULTS: LCN2, a novel biomarker in hepatic inflammation, was found to be upregulated in AOSD neutrophils by RNA sequencing and confirmed at the mRNA and protein levels. Plasma levels of LCN2 were significantly higher in AOSD patients than healthy controls, RA and SLE patients. Plasma LCN2 levels were closely correlated with inflammatory markers, systemic score, HScore and cytokines. Moreover, LCN2 levels were increased in active AOSD with liver involvement and independently associated with liver dysfunction. Enhanced expression of LCN2 was detected in liver biopsies from three patients with ongoing liver injury. Furthermore, the area under the curve value of LCN2 for identifying AOSD with liver injury from other liver diseases was 0.9694. CONCLUSION: Our results reveal that neutrophils-derived LCN2 is higher in plasma and liver tissue in AOSD patients than in healthy controls, and it could serve as a potent biomarker for identifying AOSD with systemic inflammation, especially liver damage caused by hyperinflammation.
Assuntos
Lipocalina-2/metabolismo , Fígado/metabolismo , Doença de Still de Início Tardio/metabolismo , Adulto , Biomarcadores/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Lipocalina-2/sangue , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Índice de Gravidade de Doença , Doença de Still de Início Tardio/sangue , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/patologiaRESUMO
In the last decades, there has been an increasing concern about the human exposure to indoor dust. Therefore, it is imperative to assess the toxicity of indoor dust and associated dust extracts. In this study, the acute toxicity assessment of indoor dust was performed using a bioluminescence test, with Photobacterium phosphoreum T3 (PPT3) chosen as the test bacterium. The different indoor dust samples were collected from residences, offices, dormitories and laboratories in Shanghai, China. Our data reveal that PPT3 is more active to water-soluble ions and organic contaminants at low concentrations, while extract solutions elicit increased bacterial toxicity at high concentrations. The results of a bioluminescence assay by PPT3 indicated that the dust organic extracts exhibited increased toxicity compared with the water exacts. Dust extracts from the laboratory exhibited the greatest bacterial toxicity when compared with office, dormitory and residence samples. Moreover, office dust exhibited higher bacterial toxicity than residence dust. Furthermore, the comprehensive toxicity of dust on PPT3 was assessed by extracts toxicity -addition (i.e. IRaddition). The calculated values were close to the corresponding experimental data. The bioluminescence test showed the indoor dust samples are weakly toxic to PPT3, which are equivalent to 0.046-0.123 mg Hgâ¢L-1. Different dust extracts among the different sampling sites showed varying toxicity to PPT3. This study provides some important information to understand the potential health risk from different indoor environment using a rapid bioluminescence assay.
Assuntos
Poluição do Ar em Ambientes Fechados , Poeira , Poluição do Ar em Ambientes Fechados/análise , China , Poeira/análise , Humanos , Photobacterium , Extratos VegetaisRESUMO
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorder among females of reproductive age. Many emerging contaminants in personal care products have been confirmed with endocrine disruptive effects. We performed a case-control study to explore the association between the concentrations of certain emerging contaminants (organic UV filters, bisphenol A, and triclosan) and the risk of PCOS. Urine samples were collected from 40 women with PCOS (case group) and 83 healthy women (control group). No significant differences were found in detection rate or total concentrations of analytes in women with PCOS and controls (pâ¯>â¯0.05). In addition, no association was found between certain emerging contaminants and PCOS either in an unadjusted binary logistic regression model or in a model adjusted for potential confounders. However, with stratification according to body mass index, one organic UV filter - octocrylene(OC) was significantly associated with PCOS in women with BMI ≥â¯24 (adjusted OR = 1.512, 95% CI: 1.043, 2.191). It's the first time to investigate the association between exposure of organic UV filters and PCOS risk. We conclude that there is positive association between OC and PCOS risk in obese and overweight women.