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Bilateral diffuse metastatic lung adenocarcinoma (BLDM-LUAD) is a special imaging pattern of lung adenocarcinoma (LUAD). We retrospectively assessed survival outcomes and co-mutation characteristics of BLDM-LUAD patients harboring epidermal growth factor receptor (EGFR) mutations who were treated with EGFR-yrosine kinase inhibitors (TKIs). From May 2016 to May 2021, among 458 patients who submitted samples for next generation sequencing (NGS) detection in 1125 patients with non-small-cell lung cancer (NSCLC), and 44 patients were diagnosed as BLDM-LUAD. In order to analyze the survival outcomes of BLDM-LUAD patients harboring EGFR mutations who were treated with EGFR-TKIs, the factors age, gender, smoking history, hydrothorax, site of EGFR mutations and EGFR-TKIs treatment were adjusted using propensity score-matching (PSM). The Kaplan-Meier survival curves and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The co-mutation characteristics of BLDM-LUAD patients harboring EGFR mutations were analyzed by NGS panels. 64 patients with advanced lung adenocarcinoma harboring EGFR mutations and first-line treatment of EGFR-TKIs were successfully matched. BLDM-LUAD (n = 32) have significantly longer median PFS than control group (n = 32) (mPFS: 14 vs 6.2 months; p = .002) and insignificantly longer median OS than control group (mOS: 45 vs 25 months; p = .052). The patients with BLDM-LUAD have the higher frequency of EGFR mutation than control group (84.1% vs 62.0%) before PSM. The co-mutation genes kirsten rat sarcoma viral oncogene homolog (KRAS) (9.4%), ataxia telangiectasia-mutated (ATM) (7.4%) and mesenchymal-epithelial transition (MET) (3.1%) only appeared in the control group after PSM. The BLDM-LUAD harboring EGFR mutations was associated with a favorable prognosis to EGFR-TKI.
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Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutação , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Estudos RetrospectivosRESUMO
Cervical cancer is a common malignancy among women worldwide. Long non-coding RNAs (lncRNAs) are frequently involved in the pathogenesis of cervical cancer. Therefore, the present study aimed to investigate the potentials of lncRNA799 in cervical cancer. mRNA and protein expression were detected by reverse transcription-quantitative polymerase chain reaction and Western blot analysis, respectively. Cellular functions were assessed using CCK-8, wound healing and transwell analysis. The binding potential of zinc finger E-box-binding homeobox 1 (ZEB1) on the promoter of lncRNA799 was predicted utilizing the JASPAR database, and was then verified by luciferase and chromatin immunoprecipitation (ChIP) assays. Furthermore, the gene interactions were assessed using RNA immunoprecipitation and co-immunoprecipitation assays. The results demonstrated that lncRNA799 was upregulated in cervical cancer cells. However, lncRNA799 deficiency suppressed the proliferation and epithelial-mesenchymal transition of cervical cancer cells. Furthermore, lncRNA799 could interact with eukaryotic translation initiation factor 4A3 to maintain the mRNA stability of transducin (ß)-like 1 X-linked receptor 1 (TBL1XR1) and promote the interaction between ZEB1 and TBL1XR1. Additionally, the results showed that ZEB1 could transcriptionally activate lncRNA799. Taken together, the present study suggested that the lncRNA799/TBL1XR1/ZEB1 axis could form a positive feedback loop in cervical cancer and could be, therefore, considered as a potential therapeutic strategy for cervical cancer.
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MicroRNAs , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , MicroRNAs/genética , Retroalimentação , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Repressoras/genética , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismoRESUMO
(Z)-alkenes are useful synthons but thermodynamically less stable than their (E)-isomers and typically more difficult to prepare. The synthesis of 1,4-hetero-bifunctionalized (Z)-alkenes is particularly challenging due to the inherent regio- and stereoselectivity issues. Herein we demonstrate a general, chemoselective and direct synthesis of (Z)-2-butene-1,4-diol monoesters. The protocol operates within a Pd-catalyzed decarboxylative acyloxylation regime involving vinyl ethylene carbonates (VECs) and various carboxylic acids as the reaction partners under mild and operationally attractive conditions. The newly developed process allows access to a structurally diverse pool of (Z)-2-butene-1,4-diol monoesters in good yields and with excellent regio- and stereoselectivity. Various synthetic transformations of the obtained (Z)-2-butene-1,4-diol monoesters demonstrate how these synthons are of great use to rapidly diversify the portfolio of these formal desymmetrized (Z)-alkenes.
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The fabrication of molecular crystalline materials with fast, multistimuli-responsive behavior and the construction of the corresponding structure-activity relationship are of extraordinary significance for the development of smart materials. In this context, three multistimuli-responsive functional metal-organic polyhedra (MOP), {[Dy2(bcbp)3(NO3)1.5(H2O)7]·Cl4.2·(NO3)0.3·H2O}n (1), {[Dy2(bcbp)4(H2O)8]Cl6}n (2), and {[Eu2(bcbp)4(H2O)10]Cl6·H2O}n (3; bcbp = 1,1'-bis(4-carboxyphenyl)-4,4'-bipyridinium), were successfully prepared and characterized. All of the compounds exhibit rapid and reversible photochromic and electrochromic dual-responsive behaviors. Furthermore, benefiting from the well-defined crystal structure and different responsive behaviors, the photoinduced electron transfer (PIET) process and structure-activity relationship were explored. In addition, considering the excellent photochromic performance, function filter paper and smart organic glass were successfully prepared and used for ink-free printing and UV light detection.
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Anthocyanin is one important nutrition composition in Tartary buckwheat (Fagopyrum tataricum) sprouts, a component missing in its seeds. Although anthocyanin biosynthesis requires light, the mechanism of light-induced anthocyanin accumulation in Tartary buckwheat is unclear. Here, comparative transcriptome analysis of Tartary buckwheat sprouts under light and dark treatments and biochemical approaches were performed to identify the roles of one B-box protein BBX22 and ELONGATED HYPOCOTYL 5 (HY5). The overexpression assay showed that FtHY5 and FtBBX22 could both promote anthocyanin synthesis in red-flower tobacco. Additionally, FtBBX22 associated with FtHY5 to form a complex that activates the transcription of MYB transcription factor genes FtMYB42 and FtDFR, leading to anthocyanin accumulation. These findings revealed the regulation mechanism of light-induced anthocyanin synthesis and provide excellent gene resources for breeding high-quality Tartary buckwheat.
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Antocianinas , Fagopyrum , Regulação da Expressão Gênica de Plantas , Luz , Proteínas de Plantas , Fatores de Transcrição , Fagopyrum/genética , Fagopyrum/metabolismo , Fagopyrum/crescimento & desenvolvimento , Fagopyrum/efeitos da radiação , Antocianinas/biossíntese , Antocianinas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Perfilação da Expressão Gênica , Nicotiana/genética , Nicotiana/metabolismo , Nicotiana/crescimento & desenvolvimentoRESUMO
Watersheds are an important ecological security barrier and social and economic development area. In order to evaluate the ecological environment quality of arid and semi-arid watersheds more objectively and accurately, based on the remote sensing ecological index (RSEI), the salinity index was introduced to construct a remote sensing ecological index (AWRSEI) suitable for arid and semi-arid watersheds, and the Daihai watershed was taken as an example to analyze its applicability. Based on the AWRSEI model, four phases of Landsat TM/OLI composite images were used to quantitatively evaluate the ecological and environmental quality of the Daihai Basin from 2001 to 2020. The spatio-temporal evolution of the ecological and environmental quality of the Daihai Basin was analyzed using the coefficient of variation and spatial autocorrelation, and the cause analysis and driving factor explanation power analysis were carried out using geographic detectors. The results showed that:â the average correlation coefficient between AWRSEI and various ecological factors was 0.860, which was more representative than that of a single index component. The load positive and negative values and ranking of the first principal component were consistent with those of RSEI, the contribution rate of eigenvalues was 3.69% higher than those of RSEI, and the evaluation results were closer to the real surface conditions, which is suitable for the ecological environment quality assessment of arid watersheds. â¡ The annual average of the AWRSEI index in the Daihai Basin from 2001 to 2020 was 0.427, which indicated a poor ecological environment quality basis. During the study period, the average of AWRSEI showed a fluctuating trend and reached the highest value of 0.502 in 2020. The overall ecological environment quality improved significantly, the deterioration area decreased by 20.51%, and the improvement area increased by 12.71%. In terms of spatial distribution, the ecological environment quality of forest land in the southern and northwestern high-altitude areas of the Daihai Basin was good, whereas that in the northern and southern mid-altitude areas was poor, and that in the northern area was better than that in the southern area. ⢠The average variation coefficient of AWRSEI in the Daihai Basin was 0.280, the ecological environment quality was stable, and the overall change fluctuation was small; the high fluctuation was mainly concentrated in the southern part of the lake and the residential area. There was a significant spatial autocorrelation in the ecological environment quality of the Daihai Basin, and the high-high agglomeration area was mainly distributed in the forest area at high altitude and the cultivated land area at low altitude. Low-low concentration areas were scattered in the middle altitude area. ⣠The improvement of the ecological environment in Daihai Basin from 2001 to 2020 was mainly due to the increase in NDVI and the decrease in NDBSI and NDSI. NDVI and NDBSI were the combination with the strongest interaction and the strongest interpretation of the ecological environment. Land use was the dominant factor of AWRSEI and had the strongest explanatory power. The combination of land use and meteorological factors was the strongest interaction, and the relationship between each driving factor was enhanced.
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The number of patents increases quickly, while more and more low-quality patents are emerging. It's important to identify high-quality patents from massive data quickly and accurately for organizational R&D decision-making and patent layout. However, due to low percentage of high-quality patents, it is challenging to identify them efficiently. In order to solve above problem, we reconstruct the existing index system for identifying high-quality patents by adding 4 features from technological strength of patentees. Furthermore, we propose an improved model by integrating resampling technique and ensemble learning algorithm. First, generative adversarial networks (GAN) are used to expand minority samples. Second, Extreme Gradient Boosting algorithm (XGBoost) with Bayesian optimization (BO) is used to identify high-quality patents. For clarity, this model is called a GAN-BO-XGBoost model. To test the effectiveness of above model, we use patent data in field of lithography technology. Tenfold cross-validation is carried out to evaluate the performance between our proposed model and other models. The results show that GAN-BO-XGBoost model performs better and it's more stable than other models.
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Tartary buckwheat (Fagopyrum tataricum) is frequently employed as a resource to develop health foods, owing to its abundant flavonoids such as rutin. However, the consumption of Tartary buckwheat (TB) is limited in food products due to the strong bitterness induced by the hydrolysis of rutin into quercetin. This transformation is facilitated by the degrading enzyme (RDE). While multiple RDE isoenzymes exist in TB, the superior coding gene of FtRDEs has not been fully explored, which hinders the breeding of TB varieties with minimal bitterness. Here, we found that FtRDE2 is the most abundant enzyme in RDE crude extracts, and its corresponding gene is specifically expressed in TB seeds. Results showed that FtRDE2 has strong rutin hydrolysis activity. Overexpression of FtRDE2 not only significantly promoted rutin hydrolysis and quercetin accumulation but also dramatically upregulated genes involved in the early phase of flavonoid synthesis (FtPAL1ãFtC4H1ãFt4CL1, FtCHI1) and anthocyanin metabolism (FtDFR1). These findings elucidate the role of FtRDE2, emphasizing it as an endogenous factor contributing to the bitterness in TB and its involvement in the metabolic regulatory network. Moreover, correlation analysis revealed a positive relationship between the catalytic activity of RDE extracts and the expression level of FtRDE2 during seed germination. In summary, our results suggest that FtRDE2 can serve as a promising candidate for the molecular breeding of a TB variety with minimal bitterness.
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Fagopyrum , Quercetina , Quercetina/metabolismo , Fagopyrum/genética , Fagopyrum/metabolismo , Melhoramento Vegetal , Rutina/metabolismo , Sementes/metabolismoRESUMO
Rutin is a significant flavonoid with strong antioxidant property and various therapeutic effects. It plays a crucial role in disease prevention and human health maintenance, especially in anti-inflammatory, antidiabetic, hepatoprotective and cardiovascular effects. While many plants can synthesize and accumulate rutin, tartary buckwheat is the only food crop possessing high levels of rutin. At present, the rutin content (RC) is regarded as the key index for evaluating the nutritional quality of tartary buckwheat. Consequently, rutin has become the focus for tartary buckwheat breeders and has made considerable progress. Here, we summarize research on the rutin in tartary buckwheat in the past two decades, including its accumulation, biosynthesis and breakdown pathways, and regulatory mechanisms. Furthermore, we propose several strategies to increase the RC in tartary buckwheat seeds based on current knowledge. This review aims to provide valuable references for elevating the quality of tartary buckwheat in the future.
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Fagopyrum , Rutina , Humanos , Rutina/metabolismo , Fagopyrum/metabolismo , Biofortificação , Flavonoides/metabolismo , Redes e Vias MetabólicasRESUMO
Ginseng is a perennial herb of the genus Panax in the family Araliaceae as one of the most important traditional medicine. Genomic studies of ginseng assist in the systematic discovery of genes related to bioactive ginsenosides biosynthesis and resistance to stress, which are of great significance in the conservation of genetic resources and variety improvement. The transcriptome reflects the difference and consistency of gene expression, and transcriptomics studies of ginseng assist in screening ginseng differentially expressed genes to further explore the powerful gene source of ginseng. Protein is the ultimate bearer of ginseng life activities, and proteomic studies of ginseng assist in exploring the biosynthesis and regulation of secondary metabolites like ginsenosides and the molecular mechanism of ginseng adversity adaptation at the overall level. In this review, we summarize the current status of ginseng research in genomics, transcriptomics and proteomics, respectively. We also discuss and look forward to the development of ginseng genome allele mapping, ginseng spatiotemporal, single-cell transcriptome, as well as ginseng post-translational modification proteome. We hope that this review will contribute to the in-depth study of ginseng and provide a reference for future analysis of ginseng from a systems biology perspective.
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Ginsenosídeos , Panax , Panax/genética , Proteômica , Perfilação da Expressão Gênica , Genoma de Planta , Raízes de Plantas/metabolismoRESUMO
Tartary buckwheat is highly valued for its abundant rutin (quercetin 3-O-rutinoside). As a flavonoid glycoside, rutin is synthesized with the crucial involvement of UDP-dependent glycosyltransferases (UGTs). However, the functions and transcriptional regulation of the UGT-encoded genes remain poorly understood. This study identified a key gene, FtUFGT163, potentially encoding flavonol 3-O-glucoside (1 â 6) rhamnosyltransferase in Tartary buckwheat through omics analysis and molecular docking methods. The recombinant FtUFGT163 expressed in Escherichia coli demonstrated the capacity to glycosylate isoquercetin into rutin. Overexpression of FtUFGT163 significantly enhanced the rutin content in Tartary buckwheat. Further investigation identified a novel bZIP transcription factor, FtGBF1, that enhances FtUFGT163 expression by binding to the G-box element within its promoter, thereby augmenting rutin biosynthesis. Additional molecular biology experiments indicated that the specific positive regulator of rutin, FtMYB5/6, could directly activate the FtGBF1 promoter. Collectively, this study elucidates a novel regulatory module, termed "FtMYB5/6-FtGBF1-FtUFGT163", which effectively coordinates the biosynthesis of rutin in Tartary buckwheat, offering insights into the genetic enhancement of nutraceutical components in crops.
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Fagopyrum , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Rutina , Fagopyrum/genética , Fagopyrum/metabolismo , Fagopyrum/química , Rutina/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas , Simulação de Acoplamento MolecularRESUMO
CD52 is an important functional regulator involved in the development of human cancer. In this study, the clinical significance and biological function of CD52 in the malignant behavior of non-small cell lung cancer (NSCLC) were explored. In this study, immunohistochemical (IHC) staining was performed to determine the expression pattern of CD52 in NSCLC. Loss of function assays were used to evaluate the biological functions of CD52 in NSCLC cells in vitro and in vivo. Our data indicated that the expression of CD52 was significantly elevated in NSCLC and correlated with the patient prognosis. Functionally, downregulation of CD52 expression significantly suppressed the proliferation, migration, aerobic glycolysis and tumorigenesis of NSCLC cells. Moreover, CD52 regulated aerobic glycolysis of NSCLC cells through the AKT pathway. Furthermore, aerobic glycolysis induced by 2-DG inhibited the proliferation of NSCLC cells. In conclusion, CD52 knockdown inhibited aerobic glycolysis and malignant behavior of NSCLC cells through AKT signaling pathway, which may be employed in an alternative therapeutic target for NSCLC.
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Tartary buckwheat (Fagopyrum tataricum) is an annual coarse cereal from the Polygonaceae family, known for its high content of flavonoid compounds, particularly rutin. But so far, the mechanisms of the flavonoid transport and storage in Tartary buckwheat (TB) remain largely unexplored. This study focuses on ATP-binding cassette transporters subfamily C (ABCC) members, which are crucial for the biosynthesis and transport of flavonoids in plants. The evolutionary and expression pattern analyses of the ABCC genes in TB identified an ABCC protein gene, FtABCC2, that is highly correlated with rutin synthesis. Subcellular localization analysis revealed that FtABCC2 protein is specifically localized to the vacuole membrane. Heterologous expression of FtABCC2 in Saccharomyces cerevisiae confirmed that its transport ability of flavonoid glycosides such as rutin and isoquercetin, but not the aglycones such as quercetin and dihydroquercetin. Overexpression of FtABCC2 in TB hairy root lines resulted in a significant increase in total flavonoid and rutin content (P < 0.01). Analysis of the FtABCC2 promoter revealed potential cis-acting elements responsive to hormones, cold stress, mechanical injury and light stress. Overall, this study demonstrates that FtABCC2 can efficiently facilitate the transport of rutin into vacuoles, thereby enhancing flavonoids accumulation. These findings suggest that FtABCC2 is a promising candidate for molecular-assisted breeding aimed at developing high-flavonoid TB varieties.
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Fagopyrum , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Rutina , Rutina/metabolismo , Fagopyrum/genética , Fagopyrum/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Transporte Biológico , Flavonoides/metabolismo , Filogenia , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genéticaRESUMO
Based on the polynomial theory, the error propagation characteristics of the widely used N-step discrete Fourier transform (N-DFT) phase-shift algorithm were analyzed via theoretical analysis, under the effect of Gamma distortion and phase detuning. The results showed that the N-DFT algorithm could not simultaneously suppress both types of error. A robust linear phase-shift (RLPS) algorithm was designed, the performance of the RLPS and 8-DFT algorithms in terms of spectral response, detuning robustness, and G S / N was briefly analysis by Manuel Servin method. The Simulation analysis and comparison of the results show that the RLPS algorithm could suppress both types of error simultaneously, which exhibited better stability and accuracy than N-DFT and exponential algorithms, particularly in gradient measurement stability, peak-to-valley (PV) and root-mean-square (RMS) error suppression. Moreover, a physical experiment apparatus was built to test unidirectionally inclined plane mirror and concave mirror using the RLPS, N-DFT, and exponential algorithms. The results showed that the RLPS algorithm could significantly improve the measurement stability and accuracy in the presence of detuning and without screen Gamma calibration.
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SUMMARY OBJECTIVE To investigate the relations of T lymphocytes, cytokines, immunoglobulin E, and nitric oxide with otitis media with effusion (OME) in children and their clinical significances. METHODS Fifty children with OME treated in our hospital were enrolled in the study (observation group). Fifty healthy children were selected as control. The percentages of CD4+ and CD8+ T lymphocyte and CD4+/CD8+ ratio in peripheral blood, and the levels of cytokine (IL)-2, IL-4, IL-6, immunoglobulin E (IgE) and nitric oxide (NO) in peripheral blood and middle ear effusion (MEE) in both groups were detected. The correlations of these indexes with OME were analyzed. RESULTS The percentage of peripheral blood CD4+ and CD8+ levels, CD4+/CD8 ratio, IgE, and NO levels in the observation group were significantly higher than those in the control group (P < 0.01). In the observation group, the IL-2 and IL-6 levels, and IgE and NO levels in the MEE were significantly higher than those in peripheral blood (P < 0.01). In addition, in the observation group, the MEE IL-2 and IL-6 levels were positively correlated with peripheral blood CD4+/CD8+ ratio, respectively r = 0.366, P = 0.009; r = 0.334, P = 0.018. CONCLUSIONS The levels of peripheral blood CD4+ and CD8+ lymphocytes and MEE IL-2, IL-6, IgE, and NO levels are increased in children with OME. These indexes have provided significant clues for the diagnosis of OME in children.
RESUMO OBJETIVO Investigar as relações entre linfócitos T, citocinas, imunoglobulina E e óxido nítrico e a otite média com efusão (OME) em crianças e sua significância clínica. MÉTODOS Cinquenta crianças com OME tratadas em nosso hospital foram incluídas no estudo (grupo de observação). Selecionamos também 50 crianças saudáveis como controle. As porcentagens de linfócitos T CD4 + e CD8 + e a razão CD4+/CD8+ no sangue periférico, além dos níveis das citocinas IL-2, IL-4, IL-6, imunoglobulina E (IgE) e óxido nítrico (NO) no sangue periférico e de efusão no ouvido médio (MEE) de ambos os grupos foram medidos. A correlação desses índices com a OME foi analisada. RESULTADOS A porcentagem dos níveis de CD4+ e CD8 +, da razão CD4+/CD8+, de IgE e NO no sangue periférico do grupo de observação foram significativamente maiores do que no grupo controle (P < 0,01). No grupo de observação, os níveis de IL-2 e IL-6, IgE e NO em MEE foram significativamente maiores do que no sangue periférico (P < 0,01). Além disso, no grupo de observação, foi encontrada uma correlação positiva entre os níveis de IL-2 e IL-6 em MEE e a razão de CD4+/CD8+no sangue periférico, respectivamente, r = 0,366, P = 0,009; r = 0,334, P = 0,018. CONCLUSÃO Os níveis de linfócitos CD4 + e CD8 + no sangue periférico e IL-2, IL-6, IgE e NO em MEE são mais altos em crianças com OME. Esses índices forneceram evidências valiosas para o diagnóstico de OME em crianças.