RESUMO
BACKGROUND: Epithelial ovarian cancer (EOC) is one of the deadliest gynaecological malignancies worldwide. The aim of this retrospective study was to create a predictive scoring model based on simple immunological and inflammatory parameters to predict overall survival (OS) and progression-free survival (PFS) in patients with EOC. METHODS: We obtained 576 EOC patients and randomly assigned them to the training set (n = 405) and the validation set (n = 171) in a ratio of 7:3. We retrospectively evaluated the association between PIV and OS and PFS using a novel immunoinflammatory marker, according to the optihmal treshold of PIV, we divided the patients into two different subgroups, high PIV (PIV > 254.9) and low PIV (PIV ≤ 254.9). Pan-immune Inflammatory Value (PIV) was computed as follows: neutrophil count (109/L) × platelet count (109/L) × monocyte count (109/L)/lymphocyte count (109/L). Then developed a simple score prediction model based on several independent prognostic parameters using Cox regression analysis. We used receiver operator characteristic (ROC) curves, calibration plots, and decision analysis (DCA) curves to evaluate the performance of the model. Finally, we used Kaplan-Meier curves to ensure that the model could distinguish well between low- and high-risk groups. RESULTS: There was a significant difference in survival outcomes between high PIV (PIV > 310.2) and low PIV (PIV ≤ PIV310.2) (3-year survival rates of 61.34% and 76.71%, respectively); 5-year OS, 25.21% and 51.14%, respectively; 3-year PFS, 40.90% and 65.30%; 5-year PFS, 19.33% and 39.73%, respectively). Column plots of OS and PFS were constructed using independent prognostic factors. In the training module, the 3-, 5-, and 10-year AUCs for OS and PFS column charts were 0.713, 0.796, 0.839, and 0.730, 0.799, 0.826, respectively.In the validation cohort, the 3-, 5-, and 10-year AUCs for OS and PFS column charts were 0.676, 0.803, 0.685, and 0.700, respectively, 0.754, 0.727. The calibration curves showed good agreement between predicted survival and actual observations. The decision analysis curves also showed that the current model has good accuracy and clinical applicability. 3-year OS was 61.34% and 76.71%, respectively; 5-year OS was 25.21% and 51.14%, respectively; 3-year PFS was 40.90% and 65.30%, respectively; 5-year PFS was 19.33% and 39.73%, respectively. CONCLUSIONS: We constructed and validated a PIV-based nomogram to predict OS and PFS in EOC patients, with a view to helping gynaecologists converge on oncologists in their treatment and follow-up expertise in epithelial ovarian cancer.
Assuntos
Carcinoma Epitelial do Ovário , Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/imunologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Idoso , Inflamação , Neutrófilos/imunologia , Curva ROC , Adulto , Intervalo Livre de Progressão , Biomarcadores Tumorais/sangue , Estimativa de Kaplan-MeierRESUMO
Chronic liver diseases caused by various factors may develop into liver fibrosis (LF). Early stage of LF could be reversible. Tanshinone IIA (Tan IIA), an extract from Salvia miltiorrhiza, has been reported to be hepatoprotective. However, the potential targets and mechanism of Tan IIA in the treatment of LF are still unclear. Our study aims at the anti-LF mechanism of Tan IIA through network pharmacological analysis combined with LF-related experiments. Serum biochemical indicators and histopathological examination showed that Tan IIA could ameliorate the process of LF in the CCl4 -induced mouse model. Western blot and immunohistochemical assays showed that Tan IIA decreased the expression of Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositide 3-kinases/protein kinase B (PI3K/Akt), and nuclear factor erythroid 2-related factor/heme oxygenase-1 (Nrf2/HO-1). Compared with the model group, the Tan IIA groups increased the decreased superoxide dismutase activity and glutathione content, while decreasing the increased malondialdehyde content. These results indicate that Tan IIA may play an antioxidant role by inhibiting the expression of KRAS, PI3K/Akt, and Nrf2/HO-1 to ameliorate the progression of LF, which to some extent explains the pharmacological mechanism of Tan IIA in LF. In conclusion, our study demonstrates that Tan IIA could regulate LF via PI3K/Akt and Nrf2/HO-1 signaling pathways. It may be an effective therapeutic compound for the treatment of LF.
Assuntos
Abietanos , Fator 2 Relacionado a NF-E2 , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Heme Oxigenase (Desciclizante)/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver condition. However, the potential therapeutic benefits and underlying mechanism of nicotinate-curcumin (NC) in the treatment of NASH remain uncertain. METHODS: A rat model of NASH induced by a high-fat and high-fructose diet was treated with nicotinate-curcumin (NC, 20, 40 mg·kg- 1), curcumin (Cur, 40 mg·kg- 1) and metformin (Met, 50 mg·kg- 1) for a duration of 4 weeks. The interaction between NASH, Cur and Aldo-Keto reductase family 1 member B10 (AKR1B10) was filter and analyzed using network pharmacology. The interaction of Cur, NC and AKR1B10 was analyzed using molecular docking techniques, and the binding energy of Cur and NC with AKR1B10 was compared. HepG2 cells were induced by Ox-LDL (25 µg·ml- 1, 24 h) in high glucose medium. NC (20µM, 40µM), Cur (40µM) Met (150µM) and epalrestat (Epa, 75µM) were administered individually. The activities of ALT, AST, ALP and the levels of LDL, HDL, TG, TC and FFA in serum were quantified using a chemiluminescence assay. Based on the changes in the above indicators, score according to NAS standards. The activities of Acetyl-CoA and Malonyl-CoA were measured using an ELISA assay. And the expression and cellular localization of AKR1B10 and Acetyl-CoA carboxylase (ACCα) in HepG2 cells were detected by Western blotting and immunofluorescence. RESULTS: The results of the animal experiments demonstrated that NASH rat model induced by a high-fat and high-fructose diet exhibited pronounced dysfunction in liver function and lipid metabolism. Additionally, there was a significant increase in serum levels of FFA and TG, as well as elevated expression of AKR1B10 and ACCα, and heightened activity of Acetyl-CoA and Malonyl-CoA in liver tissue. The administration of NC showed to enhance liver function in rats with NASH, leading to reductions in ALT, AST and ALP levels, and decrease in blood lipid and significant inhibition of FFA and TG synthesis in the liver. Network pharmacological analysis identified AKR1B10 and ACCα as potential targets for NASH treatment. Molecular docking studies revealed that both Cur and NC are capable of binding to AKR1B10, with NC exhibiting a stronger binding energy to AKR1B10. Western blot analysis demonstrated an upregulation in the expression of AKR1B10 and ACCα in the liver tissue of NASH rats, accompanied by elevated Acetyl-CoA and Malonyl-CoA activity, and increased levels of FFA and TG. The results of the HepG2 cell experiments induced by Ox-LDL suggest that NC significantly inhibited the expression and co-localization of AKR1B10 and ACCα, while also reduced levels of TC and LDL-C and increased level of HDL-C. These effects are accompanied by a decrease in the activities of ACCα and Malonyl-CoA, and levels of FFA and TG. Furthermore, the impact of NC appears to be more pronounced compared to Cur. CONCLUSION: NC could effectively treat NASH and improve liver function and lipid metabolism disorder. The mechanism of NC is related to the inhibition of AKR1B10/ACCα pathway and FFA/TG synthesis of liver.
Assuntos
Aldo-Ceto Redutases , Curcumina , Hepatopatia Gordurosa não Alcoólica , Triglicerídeos , Curcumina/farmacologia , Curcumina/análogos & derivados , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Humanos , Células Hep G2 , Aldo-Ceto Redutases/metabolismo , Ratos , Masculino , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Acetil-CoA Carboxilase/metabolismo , Aldeído Redutase/metabolismo , Aldeído Redutase/antagonistas & inibidores , Dieta Hiperlipídica/efeitos adversos , Simulação de Acoplamento Molecular , Fígado/efeitos dos fármacos , Fígado/metabolismo , Metformina/farmacologia , Ratos Sprague-Dawley , Modelos Animais de Doenças , Rodanina/análogos & derivados , TiazolidinasRESUMO
BACKGROUND: Psychiatric nurses are vulnerable to the menace of negative emotions due to the nature of their work and the closed environment in which they work. In this study, we aimed to investigate the incidence and influencing factors of depression among psychiatric nurses. METHODS: A cross-sectional survey method was adopted to investigate 64 nurses working in the psychiatric department of a hospital from June 2022 to June 2023. The Beck Depression Inventory (BDI) questionnaire was administered to all included respondents, who were divided into depressed group (>4 points) and non-depressed group (≤4 points) according to the BDI scores. General sociological and disease-related characteristics of these two groups were measured, and items with significant differences were analyzed by logistic regression to derive factors that have an impact on the occurrence of depression among psychiatric nurses. RESULTS: Twelve psychiatric nurses in the surveyed hospital exhibited signs of depressive symptoms, with a rate of 18.75%. The univariate analysis unveiled differences between the depressed group and the non-depressed group in terms of daily sleep time, weekly working hours, professional title, working pressure, physical exercise, length of service, and physical condition. Further analysis through logistic regression revealed that daily sleep time, weekly working hours, and physical condition were factors affecting the occurrence of depression among psychiatric nurses. CONCLUSION: The vulnerability of psychiatric nurses to depression, which are potentially influenced by daily sleep hours, weekly working hours, and physical condition, deserves clinical attention so that countermeasures can be developed for early intervention.
Assuntos
Depressão , Recursos Humanos de Enfermagem Hospitalar , Enfermagem Psiquiátrica , Humanos , Estudos Transversais , Feminino , Adulto , Depressão/epidemiologia , Masculino , Recursos Humanos de Enfermagem Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Pessoa de Meia-Idade , Incidência , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To explore the clinical characteristics and genetic etiology of a patient with mental retardation and ejaculatory dysfunction. METHODS: A patient with mental retardation and ejaculatory dysfunction who was admitted to the First Affiliated Hospital of Air Force Military Medical University on November 18, 2021 was selected as the study subject. Clinical data of the patient were collected. Peripheral venous blood samples were collected from the patient and his parents. Whole exome sequencing (WES) was carried out for the patient, and the candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The patient, a 26-year-old male, had manifested atypical mental retardation and ejaculatory dysfunction. WES revealed that he has harbored a heterozygous variant of the ARID1B gene, namely c.5776C>T (p.Arg1926X). Sanger sequencing verified that neither of his parents has carried the same variant. The variant has been recorded in the 1000 Genomes, ExAC, gnomAD and ClinVar databases. A search of the dbSNP database suggested that the variant has a population frequency of 0.000 4%. The variant was predicted as deleterious by online software including Mutation Taster, CADD, and MutPred. Analysis with Cluster Omega online software suggested that the amino acid encoded by the variant site was highly conserved among various species. Analysis with PyMOL software suggested that the variant may affect the function of the encoded protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and ClinGen, the variant was predicted to be pathogenic. CONCLUSION: The c.5776C>T (p.Arg1926X) variant of the ARID1B gene probably underlay the mental retardation and ejaculatory dysfunction in this patient. Above finding has broadened the spectrum of the ARID1B gene variants and provided reference for the diagnosis and treatment of the patient.
Assuntos
Deficiência Intelectual , Masculino , Humanos , Adulto , Deficiência Intelectual/genética , Fatores de Transcrição/genética , Biologia Computacional , Frequência do Gene , Genômica , Proteínas de Ligação a DNA/genéticaRESUMO
BACKGROUND: Worldwide incidence and prevalence of both asthma and type 1 diabetes mellitus (T1DM) in children have been increasing in past decades. Association between the two diseases has been found in some but not in other studies. OBJECTIVE: We conducted a meta-analysis to verify such an association, and bidirectional Mendelian randomization analysis to examine the potential cause-effect relationships. METHODS: Three databases (PubMed, Embase, and Web of Science) were searched from their inception to February 1, 2021. Pooled hazard ratios (HR) or odds ratios (OR), and 95% confidence intervals, were calculated. Associations between single-nucleotide polymorphisms with childhood asthma and T1DM were selected based on genome-wide association studies. The outcome datasets were obtained from FinnGen study. We used the inverse-variance-weighted (IVW), weighted median and MR-Egger methods to estimate causal effects. To assess robustness and horizontal pleiotropy, MR-Egger regression and MR pleiotropy residual sum and outlier test were conducted. RESULTS: In meta-analysis, childhood asthma was associated with an increased risk of T1DM (HR = 1.30, 95% CI 1.05-1.61, P = .014), whereas T1DM was not associated with the risk of asthma (HR = 0.98, 95% CI 0.64-1.51, P = .941; OR = 0.84, 95% CI 0.65-1.08, P = .168). MR analysis indicated increased genetic risk of T1DM in children with asthma (OR = 1.308; 95% CI 1.030-1.661; P = .028). Analysis using the IVW method indicated no association between T1DM and genetic risk of asthma (OR = 1.027, 95%CI 0.970-1.089, P = .358). CONCLUSION: Both meta-analysis and MR study suggested that childhood asthma was a risk factor for T1DM. No epidemiological or genetic evidence was found for an association of T1DM with asthma incidence. Further studies could be carried out to leverage this newfound insight into better clinical and experimental research in asthma and T1DM.
Assuntos
Asma , Diabetes Mellitus Tipo 1 , Criança , Humanos , Asma/epidemiologia , Asma/genética , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Blood cell properties effectively reflect immune status. Basophil and CD8+ CD27+ T cell levels are correlated with narcolepsy, but their causal association is unclear. This study aims to evaluate the causality between blood cell count and narcolepsy risk at the genetic level. METHODS: Two-sample Mendelian randomization (MR) analyses were performed on 35 published blood cell properties, using genome-wide association study (GWAS) datasets and one published GWAS dataset of narcolepsy, to explore causality between blood cell count and narcolepsy risk. Inverse variance weighted, MR-Egger, and weighted median approaches were employed for the MR analysis, odds ratio (OR) calculations, and heterogeneity tests of single nucleotide polymorphisms were conducted with the TwoSampleMR package in R. Multivariable Mendelian randomization (MVMR) was used to adjust the analysis further and eliminate the mediation effect between exposures. RESULTS: Basophil counts, total basophil neutrophil counts, total neutrophil eosinophil counts, granulocyte counts, and myeloid white cell counts showed inverse associations with narcolepsy risk based on the two-sample MR analysis. MVMR confirmed that only basophil counts were significantly associated with narcolepsy risk for the blood cell properties tested (OR = 0.23, 95% confidence interval 0.08-0.62; p = 0.004, power = 99.99%). Each standard deviation increase in basophil count (0.03 per nL), compared to the median level (0.04 per nL), decreased narcolepsy risk by 77%. CONCLUSION: Higher white blood cell counts, especially basophil counts, are protective factors for narcolepsy. Basophil counts has great potential to be used as a new biomarker to shorten diagnostic delay and to monitor the therapeutic effects of treatments for narcolepsy.
Assuntos
Análise da Randomização Mendeliana , Narcolepsia , Basófilos , Diagnóstico Tardio , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
PURPOSE: Many studies have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating macrophages (TIMs) in patients with nasopharyngeal carcinoma (NPC), but the results remain controversial. Here, we performed a meta-analysis to evaluate the prognostic significance of TILs/TIMs in patients with NPC METHODS: The study was registered with PROSPERO (CRD42021234078). PubMed, Embase, and Web of Science databases were searched up to Dec 30, 2020. We reviewed studies that evaluated the relationship between TILs/TIMs and overall survival (OS), disease-free survival (DFS), or progression-free survival (PFS) in NPC. For TILs, CD3, CD4, CD8, and FOXP3 were searched as T-cell markers, CD19 and CD20 as B-cell markers, and CD56 as a natural killer cell marker. For TIMs, CD68 and CD163 were searched as total and M2 macrophage markers, respectively. RESULTS: In total, 19 studies with 3708 NPC were included in this meta-analysis. We found that high total numbers of TILs were significantly associated with favorable OS [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.38-0.57 and PFS (HR 0.48, 95% CI 0.38-0.62)]. In contrast, tumor infiltration by CD3+ T cells (HR 0.55, 95% CI 0.39-0.76), CD4+ T cells (HR 0.40, 95% CI 0.18-0.85), and CD8+ T cells (HR 0.56, 95% CI 0.34-0.93) correlated positively with OS. No significant relationship was found between survival and tumor infiltration by FOXP3+ T cells, CD68+ macrophages, or CD163+ macrophages. CONCLUSION: Our findings revealed that tumor infiltration by CD3+ , CD4+ , and CD8+ T cells could be prognostic biomarkers in NPC.
Assuntos
Linfócitos do Interstício Tumoral , Neoplasias Nasofaríngeas , Humanos , Macrófagos , Carcinoma Nasofaríngeo , PrognósticoRESUMO
BACKGROUND: Patients with nasopharyngeal cancer (NPC) differ in prognosis, even at the same stage; therefore, new biomarkers are urgently required to identify early-stage NPC patients at high risk of poor prognosis. Although Epstein-Barr virus (EBV) DNA has been used for prognosis, the value of many other biomarkers expressed during the infection cycle of EBV remains unclarified. This study aimed to evaluate the prognostic potential of EA-IgA, VCA-IgA and D-dimer in patients with NPC. METHODS: Electronic databases, including PubMed, Embase and Web of Science, were searched up to February 1, 2021. Pooled data were extracted from studies that evaluated the relationship between NPC and overall survival (OS), distant metastasis-free survival (DMFS) or disease-free survival (DFS) and then were subjected to a meta-analysis. RESULTS: Nine studies with 5729 patients were included in this meta-analysis. In patients with NPC, EA-IgA levels significantly predicted OS (HR = 1.63, 95% CI 1.07-2.48). D-Dimer levels significantly predicted OS (HR = 1.75, 95% CI 1.24-2.47) and DMFS (HR = 1.91, 95% CI 1.31-2.79). However, high levels of VCA-IgA were not associated with OS (HR = 1.24, 95% CI 0.95-1.60), DMFS (HR = 1.41, 95% CI 0.92-2.17) or DFS (HR = 2.39, 95% CI 0.78-7.26). CONCLUSIONS: The present findings reveal that EA-IgA and D-dimer, but not VCA-IgA, can be used as prognostic biomarkers in NPC.
RESUMO
BACKGROUND: Numerous individual studies have investigated the diagnostic value of EBV-DNA, EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG detection for nasopharyngeal carcinoma (NPC), but the conclusions remain controversial. This meta-analysis aimed to determine the value of EBV-DNA, EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG detection in the diagnosis of NPC. METHODS: PROSPERO registration number: CRD42019145532. PubMed, EMBASE, Cochrane Library, and Chinese data libraries (Wanfang, CNKI, and CBM) were searched up to January 2019. The pooled sensitivity, specificity, and positive likelihood, negative likelihood, and diagnostic odds ratios were conducted in this meta-analysis. Summary receiver operating characteristic curves evaluated the test-performance global summary. Publication bias was examined by Deek's funnel plot asymmetry test. RESULTS: Forty-seven studies with 8382 NPC patients (NPC group) and 15,089 individuals without NPC (Control group) were included in this meta-analysis. The sensitivity, specificity, positive likelihood (+ LR), negative likelihood (-LR), DOR and AUC of EBV-DNA in diagnosis of NPC were: 0.76 (95% CI 0.73-0.77), 0.96 (95% CI 0.95-0.97), 14.66 (95% CI 9.97-21.55), 0.19 (95% CI 0.13-0.28), 84 (95% CI 50.45-139.88), 0.96 (SE: 0.001), and 0.55 (95% CI 0.54-0.57), 0.96 (95% CI 0.96-0.97), 12.91 (95% CI 9.55-17.45), 0.35 (95% CI 0.29-0.43), 39.57 (95% CI 26.44-59.23), 0.94 (SE: 0.002) for the EA-IgA, and 0.85 (95% CI 0.84-0.85), 0.89 (95% CI 0.88-0.89), 6.73 (95% CI5.38-8.43), 0.17 (95% CI 0.12-0.23), 43.03 (95% CI 31.51-58.76), 0.93 (SE: 0.007) for the VCA-IgA, and 0.86 (95% CI 0.85-0.88), 0.87 (95% CI 0.88-0.90), 7.55 (95% CI 5.79-9.87), 0.16 (95% CI 0.13-0.19), 50.95 (95% CI 34.35-75.57), 0.94 (SE: 0.008) for the EBNA1-IgA, and 0.70 (95% CI 0.69-0.71), 0.94 (95% CI 0.94-0.95), 9.84 (95% CI 8.40-11.54), 0.25 (95% CI 0.21-0.31), 40.59 (95% CI 32.09-51.35), 0.95 (SE: 0.005) for the Rta-IgG. The EBV-DNA had larger AUC compared with other EBV-based antibodies (P < 0.05), while the difference between EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG was not statistically significant (P > 0.05). CONCLUSIONS: EBV-DNA, VCA-IgA, EBNA1-IgA and Rta-IgG detection have high accuracy in early diagnosis NPC. In addition, EBV-DNA detection has the higher diagnosis accuracy in NPC. On the other hand, EA-IgA is suitable for the diagnosis but not NPC screening.
RESUMO
OBJECTIVE: This study aims to investigate the detection rates, common symptoms and risk factors of gastroesophageal reflux disease (GERD), and laryngopharyngeal reflux disease (LPRD) at the digestive endoscopy center. METHODS: A multicenter cross-sectional survey conducted at three hospitals and a total of 565 eligible participants were enrolled. All the patients completed routine ENT examination, gastroscopy, gastroesophageal reflux questionnaire (GerdQ), reflux symptom index (RSI) and a self-designed 25-item symptoms table survey. RESULTS: Among the 565 eligible participants, the detection rates of GERD and LPRD were 18.41% (104/565) and 9.91% (56/565), respectively. The detection rate of GERD combined with LPRD was 3.19% (18/565). Among GERD and LPRD patients, males (vs. females), middle-aged and elderly patients (vs. young people), BMI ≥ 24.0 kg/m2 (vs. BMI < 24.0 kg/m2), with current smoking history (vs. no smoking), and current drinking history (vs. no drinking), lying down immediately after meal (vs. no lying down immediately after meal) were significantly higher (all p < 0.05). The most common extraesophageal symptoms in patients with GERD were dry mouth (66.35%), globus sensation (56.73%), dry throat and pharyngeal itching (55.77%). The most common extraesophageal symptoms in patients with LPRD were globus sensation (91.07%), dry throat and pharyngeal itching (83.93%), and dry mouth (82.14%). CONCLUSION: GERD and LPRD had a high detection rate at the digestive endoscopy center in Guangzhou, China. Older age, BMI ≥ 24.0 kg/m2, smoking and drinking history were risk factors for both GERD and LPRD. Neither GerdQ nor RSI scores included common extraesophageal symptoms.
Assuntos
Refluxo Laringofaríngeo , Adolescente , Idoso , Estudos Transversais , Feminino , Gastroscopia , Humanos , Hipofaringe , Refluxo Laringofaríngeo/diagnóstico , Refluxo Laringofaríngeo/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
The tolerogenic dendritic cell dysfunction is associated with the pathogenesis of immune diseases. Microbial stimulus is required in the maintenance of immune functions. This study aims to elucidate the role of Mal signal in the maintenance of DEC205+ DC (decDC) immune tolerogenic function. In this study, peripheral DCs were collected from allergic rhinitis (AR) patients and healthy control (HC) subjects to assess the functional status of decDCs. An AR murine model was developed to test the role of Mal signals in the maintenance of decDCs' functions. We observed that AR decDCs (decDCs obtained from AR patients) were incompetent in the induction of type 1 regulatory T cells (Tr1 cells). AR decDCs expressed less IL-10 than that in HC decDCs. IL-10 mRNA decayed spontaneously in AR decDCs. Tat-activating regulatory DNA-binding protein-43 (TDP43) protected IL-10 mRNA from decay. AR decDCs expressed lower levels of Mal than that in HC decDCs. Mal depletion resulted in IL-10 mRNA decay in HC decDCs. Reconstitution of Mal in AR decDCs restored the capacity of inducing Tr1 cells and attenuated experimental AR in mice. In conclusion, Mal plays a critical role in the maintenance of decDC's immune tolerogenic function. The absence or insufficient Mal signal impairs decDC's tolerogenic property. Reconstitution of Mal in AR decDCs can restore the immune tolerogenic capacity, which may have translational potential in the treatment of AR and other allergic diseases.
Assuntos
Células Dendríticas/imunologia , Glicoproteínas de Membrana/metabolismo , Receptores de Interleucina-1/metabolismo , Rinite Alérgica/imunologia , Adulto , Animais , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Tolerância Imunológica , Interleucina-10/genética , Interleucina-10/metabolismo , Masculino , Glicoproteínas de Membrana/deficiência , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Knockout , Estabilidade de RNA , RNA Mensageiro/metabolismo , Receptores de Interleucina-1/deficiência , Receptores de Interleucina-1/genética , Linfócitos T Reguladores/imunologia , Receptores Toll-Like/metabolismoRESUMO
YAP signaling has been reported to be dysregulated in numerous cancer types. However, its roles in nasopharyngeal carcinoma (NPC) are poorly understood. Although several studies have shown that FOXC2 promotes the progression of NPC, the underlying molecular mechanism remains largely unknown. Here, we have shown that FOXC2 interacted with YAP and TEAD, and activated YAP signaling. Furthermore, FOXC2-YAP signaling positively regulated the expression of Hexokinase 2 (HK2) and promoted the glycolysis. Moreover, the inhibitor of HK2, 3-BrPA effectively inhibited the tumorigenesis of NPC cells in vitro and in vivo. Collectively, our study demonstrated that FOXC2 promoted the glycolysis in progression of NPC by activating YAP signaling, and suggested that FOXC2 might be promising therapeutic target.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Glicólise/fisiologia , Neoplasias Nasofaríngeas/metabolismo , Fosfoproteínas/metabolismo , Transdução de Sinais , Proteínas Adaptadoras de Transdução de Sinal/genética , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Fatores de Transcrição Forkhead/genética , Humanos , Carcinoma Nasofaríngeo , Fosfoproteínas/genética , Transdução de Sinais/fisiologia , Fatores de Transcrição , Proteínas de Sinalização YAPAssuntos
Pólipos Nasais , Rinite Alérgica , Rinite , Sinusite , Doença Crônica , Humanos , Mucina-1 , Mucosa Nasal , UbiquitinaRESUMO
BackgroundThe biased immune reactions of the adenotonsillar tissues are not always reflected by the serum immunoglobulin E (IgE); thus, we hypothesize that the systemic atopic status may not be changed after the adenotonsillectomy (AT) in children.MethodsTwenty-five children with AT and 23 age-matched healthy children were enrolled into this study, and followed up for ~4 years. Nasal Symptoms Scores (NSS), Quality of Life Scores (QOLS), specific IgE (sIgE), cytokines, and inflammatory cell were documented in all the subjects before and after study.ResultsFourteen patients and three healthy controls had positive serum sIgE levels (>0.35 kU/l) at the study-start that was not changed by the study-end. Two patients and two sIgE-negative healthy controls showed the Dermatophagoidespteronyssinus sensitization at the study-end. NSS and QOLS showed significant improvement after the surgery in the sIgE-positive patients (P<0.05), whereas no significant changes were found in the sIgE-negative patients (P=1.00). In addition, the serum sIgE-negative patients showed significant increases in interleukin (IL)-4, IL-5, and IL-10 levels in the serum (P<0.001), although no significant differences were found post surgery (P=0.667, 0.408, and 0.714, respectively).ConclusionsOur study showed that AT did not affect the pediatric atopic status. The systemic atopy may be independent of the tonsillar and adenoid tissues in children.
Assuntos
Adenoidectomia , Hipersensibilidade/sangue , Imunoglobulina E/sangue , Tonsilectomia , Antígenos de Dermatophagoides/administração & dosagem , Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/administração & dosagem , Proteínas de Artrópodes/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Hipersensibilidade/prevenção & controle , Imunização , Inflamação/sangue , Inflamação/imunologia , Interleucina-10/sangue , Interleucina-4/sangue , Interleucina-5/sangue , Masculino , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: Button batteries have been recognized as one of the dangerous foreign bodies to children for more than 30 years, but few related studies have been published to give more concern in China. METHODS: We reported 6 cases of button battery intake as foreign body in children. The Chinese literature on button battery as foreign body in children was reviewed. RESULTS: The interval between the accidental ingestion and battery removal ranged from 6 hours to 3 days. Two patients had no sequela, 3 patients had tracheoesophageal fistulas, and 1 patient had nasal septal perforation. Twenty-eight articles about button battery as foreign body in children were obtained by Chinese-language literature searches including 25 case reports, 2 health education articles, and 1 imaging article. In total, 172 cases of button battery intake as foreign body in children were identified, 23 and 10 of the 159 cases involving nasal button battery lodgment developed nasal septal perforation and nasal adhesion, respectively. Tracheoesophageal fistula was identified in 4 of the 12 ingestion cases. One case of button battery intake was in external auditory canal. CONCLUSIONS: A small number of children with button battery as foreign body were reported in China, which is 1 of the biggest countries with large population of children.
Assuntos
Corpos Estranhos/epidemiologia , Queimaduras Químicas/etiologia , Criança , Pré-Escolar , China/epidemiologia , Transtornos de Deglutição/etiologia , Meato Acústico Externo , Ingestão de Alimentos , Fontes de Energia Elétrica , Epistaxe/etiologia , Esofagite/etiologia , Feminino , Corpos Estranhos/complicações , Humanos , Lactente , Masculino , Perfuração do Septo Nasal/etiologia , Fístula Traqueoesofágica/etiologiaRESUMO
BACKGROUND: B7-H3 protein is an important regulator of the adaptive immune response in human tumorigenesis. 4-1BB is a co-stimulatory receptor expressed on activated CD8+ T cells, and regulates T cell immunity. Here, we investigated the role of B7-H3 in the growth and invasion of nasopharyngeal carcinoma (NPC) and the effect of its interaction with 4-1BB on tumor immunity. METHODS: Short hairpin (sh) RNA was designed to knock down B7-H3 expression in NPC cells. NPC cells with stable knockdown of B7-H3 were established and injected into nude mice. The effects of B7-H3 on cell proliferation, apoptosis, and epithelial-to-mesenchymal transition (EMT) were detected by the CCK8 assay, flow cytometry, TUNEL assay, and western blot analysis. The migration and invasion abilities were determined using the Transwell assay and scratch assay. Co-immunoprecipitation (Co-IP) assays were performed to study the interaction between B7-H3 and 4-1BB. Anti-4-1BB antibody was used in a co-culture system and xenograft mice to study the effect of 4-1BB on NPC development. RESULTS: NPC cells transfected with sh-B7-H3 showed a higher rate of apoptosis, slower growth rate, impaired migration, and less EMT in vitro. Xenograft mice with stable knockout of B7-H3 had lower tumor burdens, and the stripped tumors had lower rates of cell proliferation, higher rates of apoptosis, and less EMT in vivo. Additionally, decreased B7-H3 expression was positively correlated with interferon-γ, tumor necrosis factor-α, and 4-1BB+CD8+ tumor-infiltrating lymphocytes. Co-IP studies showed that B7-H3 interacts with 4-1BB. Also, the inhibitory effects of sh-B7-H3 on NPC tumor growth, invasion, and tumor immunity could be alleviated by the anti-4-1BB antibody both in vivo and in vitro. CONCLUSION: Our findings suggest that B7-H3 may accelerate tumor growth, tumor cell invasion, and EMT, and interact with 4-1BB to produce CD8+ T cell exhaustion that inhibits tumor immunity. B7-H3 might serve as a novel target for treating NPC.
Assuntos
Antígenos B7 , Linfócitos T CD8-Positivos , Proliferação de Células , Transição Epitelial-Mesenquimal , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Antígenos B7/genética , Antígenos B7/metabolismo , Antígenos B7/imunologia , Animais , Humanos , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Linfócitos T CD8-Positivos/imunologia , Camundongos , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/imunologia , Camundongos Nus , Apoptose , Progressão da Doença , Movimento Celular , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Exaustão das Células TRESUMO
Background: This study used functional near-infrared spectroscopy (fNIRS) to investigate brain activation patterns in children with attention deficit hyperactivity disorder (ADHD) with and without additional comorbidities to identify disease-related biomarkers by the neuroimaging that will facilitate to make a diagnosis decision. Methods: In this study, 165 medication-naive children aged 7 to 15 years were recruited and categorized into four groups: ADHD, ADHD with learning disabilities (ADHD&LD), ADHD with oppositional defiant disorder (ADHD&ODD), and healthy controls. A multichannel fNIRS system was used to monitor hemodynamic changes at rest state in the prefrontal and temporal lobes of the brain. The amplitude of a low-frequency fluctuation (ALFF) matrix was calculated by summation and averaging of the square root of the signal power spectrum. One-way analysis of variance was used to identify statistical differences between channels. Results: All ADHD children presented significantly higher ALFF values in different brain regions when compared with the healthy controls. Patients with ADHD&LD exhibited higher ALFF values in the medial prefrontal cortex (P Ch38 = .01, P Ch48 = .01), temporal cortex (P Ch22 = .04, P Ch41 = .002, P Ch51 = .001), and the left ventrolateral prefrontal cortex (P Ch39 = .0009, P Ch50 = .001), whereas ADHD&ODD children were not significantly different to those diagnosed with ADHD. Conclusions: ADHD with learning disabilities (LD) possessed a different pathogenesis from ADHD, manifested as lower functional brain activity in the medial prefrontal cortex, temporal cortex, and the left ventrolateral prefrontal cortex, while ADHD&ODD did not present significant changes compared with ADHD. ODD-related symptoms may be part of ADHD symptoms rather than being an independent disorder.