Coffee consumption might be associated with lower potential risk and severity of metabolic syndrome: national health and nutrition examination survey 2003-2018.

BACKGROUND: Metabolic syndrome (MetS) is a clinical syndrome characterized by multiple metabolic disorders and is a serious global health problem. The coffee effect, acting as one of the most prevalent beverages on metabolic syndrome, is debatable. METHODS: We included patients from the National Health and Nutrition Examination Survey 2003-2018 and used a comprehensive evaluation called the MetS z-score to assess the severity of metabolic syndrome. The relationship between coffee, decaffeinated coffee, tea, and MetS z-scores was explored using a weighted linear regression. We also divided the participants into metabolic and non-metabolic syndrome groups according to the NCEP/ATP III criteria for the subgroup analysis. RESULTS: A total of 14,504 participants were included in this study. The results demonstrated that drinking more than three cups of coffee daily was significantly linked to lower MetS z-scores (p < 0.001). Daily coffee consumption was also associated with lower BMI (p = 0.02), systolic blood pressure (p < 0.001), Homeostatic Model Assessment for Insulin Resistance (p < 0.001), and triglycerides (p < 0.001), while it was positively correlated with HDL-C (p = 0.001). Participants who consumed more than three cups of coffee daily had a lower MetS z-score in the MetS (p < 0.001) and non-MetS (p = 0.04) groups. CONCLUSION: This research indicates that coffee consumption is linked to MetS severity. However, decaffeinated coffee and tea intake were unrelated to MetS severity.

Exploration of the association between new "Life's Essential 8" with hyperuricemia and gout among US adults.

BACKGROUND: Previous researches have reported the relationship between uric acid and cardiovascular disease. We aimed to investigate the association of Life's Essential 8, a recently updated measurement of cardiovascular health, with the prevalence of hyperuricemia (HUA) and gout among US adults. Additionally, we also explored the relationship between LE8 and all-cause mortality among patients with HUA or gout. METHODS: Participants from the National Health and Nutrition Examination Survey in 2007-2016 were involved in this study. LE8 score was categorized into low, moderate, high CVH groups according to American Heart Association definitions. Multivariable logistic regression and cox regression analyses, restricted cubic spline models, subgroup analysis and sensitivity analysis were used to explore the associations. RESULTS: A total of 23,619 adult participants were included in this study, which included 4,775 hyperuricemia patients and 1,055 gout patients. Among all participants, the overall median LE8 score was 65.62 (21.25) and the prevalence of hyperuricemia and gout of were 20.2% and 4.5%, respectively. After fully adjusted the potential confounders, participants in high CVH group had a lower prevalence of hyperuricemia and gout compared with the low CVH group, with a OR (95%CI) of 0.50 (0.39-0.63) and 0.50 (0.30-0.82), respectively. The restricted cubic spline showed a significantly inverse relationship between LE8 and hyperuricemia and gout. Similar patterns were also identified in the association between LE8 scores and all-cause mortality in HUA and gout patients. CONCLUSIONS: Higher LE8 scores are associated with lower risk and lower all-cause mortality of HUA and gout among US adults. Adherence to optimal CVH metrics may be an appropriate prevention and management strategy for reducing the socioeconomic burden of hyperuricemia and gout.

Micro-inflammation related gene signatures are associated with clinical features and immune status of fibromyalgia.

BACKGROUND: Fibromyalgia (FM) is a multifaceted disease. Along with the genetic, environmental and neuro-hormonal factors, inflammation has been assumed to have role in the pathogenesis of FM. The aim of the present study was to explore the differences in clinical features and pathophysiology of FM patients under different inflammatory status. METHODS: The peripheral blood gene expression profile of FM patients in the Gene Expression Omnibus database was downloaded. Differentially expressed inflammatory genes were identified, and two molecular subtypes were constructed according to these genes used unsupervised clustering analysis. The clinical characteristics, immune features and pathways activities were compared further between the two subtypes. Then machine learning was used to perform the feature selection and construct a classification model. RESULTS: The patients with FM were divided into micro-inflammation and non-inflammation subtypes according to 54 differentially expressed inflammatory genes. The micro-inflammation group was characterized by more major depression (p = 0.049), higher BMI (p = 0.021), more active dendritic cells (p = 0.010) and neutrophils. Functional enrichment analysis showed that innate immune response and antibacterial response were significantly enriched in micro-inflammation subtype (p < 0.050). Then 5 hub genes (MMP8, ENPP3, MAP2K3, HGF, YES1) were screened thought three feature selection algorithms, an accurate classifier based on the 5 hub DEIGs and 2 clinical parameters were constructed using support vector machine model. Model scoring indicators such as AUC (0.945), accuracy (0.936), F1 score (0.941), Brier score (0.079) and Hosmer-Lemeshow goodness-of-fit test (χ2 = 4.274, p = 0.832) proved that this SVM-based classifier was highly reliable. CONCLUSION: Micro-inflammation status in FM was significantly associated with the occurrence of depression and activated innate immune response. Our study calls attention to the pathogenesis of different subtypes of FM.

On-chip ytterbium-doped lithium niobate waveguide amplifiers with high net internal gain.

Integrated optical systems based on lithium niobate on insulator (LNOI) have shown great potential in recent years. However, the LNOI platform is facing a shortage of active devices. Considering the significant progress made in rare-earth-doped LNOI lasers and amplifiers, the fabrication of on-chip ytterbium-doped LNOI waveguide amplifiers based on electron-beam lithography and inductively coupled plasma reactive ion etching was investigated. The signal amplification at lower pump power (<1 mW) was achieved by the fabricated waveguide amplifiers. A net internal gain of ∼18 dB/cm in the 1064 nm band was also achieved in the waveguide amplifiers under a pump power of 10 mW at 974 nm. This work proposes a new, to the best of our knowledge, active device for the LNOI integrated optical system. It may become an important basic component for lithium niobate thin-film integrated photonics in the future.

[Utility of thromboelastography in the treatment of acquired hemophilia A].

Acquired hemophilia A (AHA) is a bleeding disorder caused by the spontaneous development of inhibitory autoantibodies to factor VIII. Thromboelastography (TEG) is a clinical examination that assesses clot formation in the whole blood. However, its utility in the hemostatic management of AHA is unexplored. A 35-year-old man who developed AHA after abdominal surgery was treated for hemostasis with bypassing agents. The TEG R value, which was prolonged as bleeding worsened, was improved by switching to bypassing agents. We report this impressive case, which suggests that TEG can monitor hemostatic effects and is useful for the management of a bypassing agent regimen in addition to its previously acknowledged utility in clinical evaluation.

Clinical characteristics, outcome and prognostic factors in critically ill patients with lupus nephritis.

OBJECTIVES: To describe the clinical characteristics and outcome of patients with lupus nephritis (LN) in intensive care unit (ICU), identify prognostic factors and construct a predictive model of in-ICU survival. METHODS: A total of 505 ICU admissions of lupus patients were screened and LN patients confirmed by renal biopsy were enrolled. Clinical characteristics and outcome of patients in ICU were collected. A logistic regression analysis was performed to identify independent prognostic factors and a nomogram was plotted to construct a predictive model. RESULTS: A total of 70 patients with LN were enrolled. The median age of the patients was 28.5 years, and the median course of LN was two months. Renal pathology classes indicated that 38 patients were class IV, 11 were class IV+V, and 10 were class III. The most common primary cause of ICU admission was infection in 40 patients, followed by LN in 11 patients. Forty-one patients died in ICU. The multivariate analyses revealed that lactic acid (OR 1.682 [2.130-17.944], p=0.001), gamma-glutamyl transpeptidase (OR 1.057 [1.009-1.107], p=0.020), APACHE II (OR 3.852 [1.176-12.618], p=0.026), vasopressor (OR 10.571 [1.615-69.199], p=0.014) and platelet count (OR 0.967 [0.941-0.993], p=0.013) were independently associated with ICU survival of critical LN patients. A predictive model was constructed and validated. CONCLUSIONS: This study is the first to elucidate the features and identify prognostic factors in critically ill patients with LN. These findings could help clinicians to early identify high-risk patients of mortality, which consequently may reduce the mortality of critically ill patients with LN.

Decisional control preference among Chinese patients with advanced kidney disease: the role of mastery, perceived social support and self-efficacy.

Although previous studies have shown a correlation between mastery, self-efficacy, and perceived social support among Chinese patients with advanced kidney disease, few studies have examined their relationship pathways. This study aimed to examine decisional control preference and the relationship between mastery, perceived social support, and self-efficacy among patients with advanced chronic kidney disease. A cross-sectional survey was conducted, and 350 participants were investigated using Control Preference Scale, Personal Mastery Scale, Perceived Social Support Scale, and Self-efficacy Scale. The mediating relationships were determined via structural equation modeling. Results showed that education and economic status were demographic factors influencing patients' decisional control preference. The model showed that mastery and self-efficacy had a direct effect on decisional control preference while perceived social support had an indirect effect mediated via mastery and self-efficacy. Therefore, improving self-efficacy can increase patient willingness to involve in medical decision-making. This study provides new interventions and future directions for promoting decisional control preference.

Harnessing Reversible Wetting Transition to Sweep Contaminated Superhydrophobic Surfaces.

Sweeping deposited particles is absolutely essential in order to maintain the excellent functionality of superhydrophobic surfaces. Many methods have been proposed to sweep microparticles deposited on tips of micro/nanostructures. However, how to sweep nanoparticles trapped in cavities of superhydrophobic surfaces has remained an outstanding issue. Here, we show that harnessing the reversible wetting transition provides a feasible way to sweep such nanoparticles. Using molecular dynamics simulations, we demonstrate that the electrically induced CB-W wetting transition makes liquid intrude into a groove and wet a trapped hydrophilic nanoparticle; however, once the electric field is removed, a spontaneous W-CB dewetting transition happens, and the extruded liquid transports the hydrophilic nanoparticle to the groove top, successfully picking up the trapped hydrophilic nanoparticle. We further find that the adhesion between the nanoparticle and groove bottom wall hinders the successful pickup, and picking up such a nanoparticle requires a stronger particle hydrophilicity. With the introduction of amphiphilic Janus particles into a liquid, we exhibit that the electrically induced reversible wetting transition can also successfully pick up a trapped hydrophobic nanoparticle. By means of calculations of the potential of mean force (PMF), we reveal pathways of both the CB-W wetting transition and the W-CB dewetting transition and hence answer why and how a hydrophilic or a hydrophobic nanoparticle is picked up successfully.

Effects of Nanodroplet Sizes on Wettability, Electrowetting Transition, and Spontaneous Dewetting Transition on Nanopillar-Arrayed Surfaces.

In this study, the wetting and dewetting behaviors of water nanodroplets containing various molecule numbers on nanopillar-arrayed surfaces in the presence or absence of an external electric field are investigated via molecular dynamics (MD) simulations, aiming to examine whether there is a scale effect. The results show that, in the absence of an electric field, nanodroplets on coexisting Cassie/Wenzel surfaces may be in the Cassie or the Wenzel state depending on their initial states, and apparent contact angles of the Cassie or Wenzel nanodroplets increase monotonously with increasing the droplet size. Energy analysis shows that on the same coexisting Cassie/Wenzel surface, when an electric field is imposed, a small nanodroplet possesses a lower energy barrier separating the Cassie state from the Wenzel state. Therefore, the small nanodroplet is easier to collapse into the Wenzel state. Moreover, the spontaneous Wenzel-to-Cassie dewetting transition is not observed for the nanodroplets after the removal of the electric field because the Wenzel state is a globally stable energetic state. With the same pillar geometry, both the wetting transition and the dewetting transition are significantly modified for liquids with higher intrinsic contact angles. The energy barrier of the wetting transition increases for both the large and small nanodroplets, meaning that the Cassie state becomes more robust. The energy curve shows that the Wenzel state of the large nanodroplet has higher energy so that the droplet can return to the Cassie state when removing the electric field. Intriguingly, although the small Wenzel nanodroplet has lower energy in the presence of the electric field, the dewetting transition still occurs. The increased solid-liquid interfacial tension when removing the electric field is responsible for this abnormal result. The wetting and dewetting transitions follow different energy pathways, leading to a hysteresis energy loop. There exists a critical water molecule number separating the unstable/stable Wenzel configurations, above which the Cassie state is energetically favorable and the dewetting transition can occur spontaneously after removing the electric field.

Wetting Transition from the Cassie-Baxter State to the Wenzel State on Regularly Nanostructured Surfaces Induced by an Electric Field.

When droplets are placed on hydrophobic textured surfaces, different wetting states Cassie-Baxter (CB) state or Wenzel (W) state may occur depending on materials and structures of surfaces, types and sizes of droplets, thermal fluctuations, and external stimuli. The wetting transition from the CB to the W state and the opposite process have attracted a great deal of attention because of their primary importance for designing and fabricating textured surfaces. In this work, molecular dynamics (MD) simulations are employed to understand the mechanism behind the CB-to-W transition for a nanoscale water film placed on a surface decorated with a single nanogroove when an external electric field is applied. The free energy variation during the transition process is computed on the basis of the restrained MD simulations. Water intrusion into the groove is observed by simulation snapshots, which provides direct evidence for the electric field-induced CB-to-W transition. In the previous experiments, however, only a sharp reduction in the apparent contact angle is employed to judge whether the transition takes place. The free energy curves reveal that there are two energy barriers separating the CB and W states (Δ E1) as well as separating the W and CB states (Δ E2). Owing to the presence of Δ E1, although the CB state has a higher free energy than the W state, it cannot spontaneously convert to the W state. When the external energy input exceeds Δ E1, the CB-to-W transition can be triggered, otherwise the transition will stop, and the water film will return to the CB state. Moreover, it is found that the maximum of free energy always occurs after the film touches the groove bottom. Thus, the requirement that the film should touch the groove bottom is responsible for the presence of the energy barrier Δ E1. Finally, the dependence of the two energy barriers on the electric field strength, groove aspect ratio, and intrinsic contact angle of the groove is also discussed.

Lower Serum Uric Acid Levels May Lower the Incidence of Diabetic Chronic Complications in U.S. Adults Aged 40 and Over.

Previous studies have generally reported the association between serum uric acid (SUA) and diabetic complications, but large-scale research exploring the above association in U.S. adults with diabetes is limited. To explore the association between SUA and chronic complications of diabetes among U.S. patients aged ≥40, we used data from the National Health and Nutrition Examination Survey 1999−2008. SUA was divided into three levels: T1 (SUA ≥ 420 µmol/L), T2 (300 ≤ SUA < 420 µmol/L), and T3 (SUA < 300 µmol/L). Binary logistic regression and restricted cubic spline analysis were applied to evaluate the association between SUA and chronic complications of diabetes. A trend test was performed as the SUA increased substantially. After full-adjusted confounding factors, patients in the T3 group had a lower risk of diabetic kidney disease, cardiovascular disease, and peripheral neuropathy compared with the T1 group, with a OR (95% CIs) of 0.33 (0.21−0.52), 0.56 (0.36−0.87), and 0.49 (0.27−0.89), respectively. The restricted cubic spline showed a significant positive relationship between SUA and cardiovascular disease and diabetic kidney disease in diabetes patients, but not peripheral neuropathy. Maintaining a SUA of less than 300 µmol/L might be protective against the risk of cardiovascular disease, diabetic kidney disease, and peripheral neuropathy other than diabetic retinopathy compared with a SUA of more than 420 µmol/L in U.S. diabetes patients aged 40 and over.

Association between Coffee Consumption, Caffeine Intake, and Metabolic Syndrome Severity in Patients with Self-Reported Rheumatoid Arthritis: National Health and Nutrition Examination Survey 2003-2018.

Rheumatoid arthritis (RA) is chronic inflammatory disease. Although coffee impacts metabolism, no evidence has shown an association between coffee consumption and decreased risk for developing metabolic syndrome (MetS) among RA patients. Hence, we examined the association between coffee consumption and metabolic syndrome severity among 1094 participants with self-reported RA. Accordingly, patients with MetS z-scores of <0 and ≥0 were designated as low- and high-risk groups, respectively. In the fully adjusted model, drinking over two cups of coffee daily was associated with a decrease in the MetS z-score (p = 0.04). Subgroup analysis showed that in the low-risk group, daily intake of <2 cups of coffee was associated with low MetS z-scores (p = 0.003), scores (p = 0.03). Coffee intake was associated with low body mass index (p = 0.03 for 0−2 cups per day; p = 0.02 for >2 cups per day) and low HOMA-IR (ß, −2.62; 95%CI, −5.13 to −0.11; p = 0.04). Our study suggests that coffee, but not decaffeinated coffee consumption and total caffeine intake, is associated with MetS severity in RA.

QRISK3-based analysis of cardiovascular risk factors in patients with long-term but well-controlled systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem inflammatory disease of unknown etiology. Corticosteroids and immunosuppressive agents are the principal forms of treatment for this condition. While cardiovascular disease (CVD) is known to be a major cause of death in patients with SLE, there has been no improvement over the last few decades with regard to diagnosis, treatment, or prognosis. The QRISK3 algorithm is a new algorithm that includes SLE-related risk factors; this tool can predict the risk of CVD over a ten-year period. In this study, involving 180 patients, we compared the performance of the Framingham risk score, the recalibrated risk prediction SCORE, and QRISK3 for the assessment of CVD in patients with a long course of disease and low disease activity. Then, we used a more efficient algorithm, QRISK3 to identify the risk factors for CVD. This was a prospective and cross-sectional study involving 116 patients. All patients fulfilled the ACR criteria. The systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) is widely used to assess disease activity in SLE patients; patients with a SLEDAI-2K less than or equal to 4 are considered to be stable. Thus, we defined well-controlled patients as those with a SLEDAI-2K score less than or equal to 4. The dose of glucocorticoid (GC) that patients received was less or equal to 10 mg per day. We recorded and assessed a range of traditional risk factors, current treatments, comorbidities, data at the time of onset, and SLE-related evaluations. The QRISK3 score, and the relative risk (RR) that this score defined, were used to estimate the risk of CVD in patients with SLE. According to these relative risks, the patients were divided into low- (n=28), intermediate- (n=46), and high-relative risk (n=31) groups for subgroup analysis. Of the 116 patients enrolled, 105 were eligible to be assessed for the risk of CVD. By univariate analyses, the RR was significantly related with age at the time of enrolment (p<0.001), age at onset (p<0.001), resting heart rate (RHR) (p<0.001), present dose of GCs (p<0.001), present SLEDAI-2K (p=0.015), aerobic exercise (p<0.001), initial SLEDAI-2K (p<0.001), and initial dose of GCs (p=0.048). In the multiple linear regression model, the RR of CVD was significantly correlated with the initial SLEDAI-2K score (ß=2.112, p<0.001), initial dose of GCs (ß=-0.009, p=0.041), resting heart rate (ß=0.241, p=0.003) and age at onset (ß=-0.208, p=0.004). Pearson's correlation showed that RHR was significantly associated with aerobic exercise (r=-0.322, p=0.001). Subgroup analysis further identified a positive correlation between the history of nephritis, metabolic syndrome (MetS), aerobic exercise, present dose of GCs, and the RR of CVD. Patients with long-term but well-controlled SLE had a high relative risk of CVD and that this was associated with resting heart rate (P=0.003), history of lupus nephritis (P<0.001), initial SLEDAI-2K score (P<0.001), and metabolic syndrome (P=0.017). However, age at onset (P<0.001), use of hydroxychloroquine (P=0.30) and Mycophenolate mofetil (P=0.01), and the initial dose of glucocorticoid (P=0.049), were protective factors. Younger SLE patients had a significantly higher relative risk of CVD than older patients (p<0.001). QRISK3 detected more SLE patients at high risk of CVD when compared to the Framingham and recalibrate SCORE. To reduce the risk of CVD in SLE patients, measures should be taken both during the initial stages of disease and for long-term management.

One-step high-yield preparation of nitrogen- and sulfur-codoped carbon dots with applications in chromium(vi) and ascorbic acid detection.

In this research, a nitrogen- (N) and sulfur- (S) codoped carbon dot (CDs-IPM)-based sensor was synthesized using a single-step hydrothermal method. Specifically, microcrystalline cellulose (MCC) was the main raw material, which was extracted from banana pseudo-stem-based waste, while autonomous sulfonic acid-functionalized ionic liquid (SO3H-IL) and polyethylene glycol 400 (PEG 400) acted as the N, S dopant, and surface modifier, respectively. Comprehensive spectroscopic characterization of the synthesized CDs-IPM revealed the introduction of S, N atoms in the matrix with existence of surface oxygenic functional groups. The CDs-IPM possessed enhanced photoluminescence (PL) intensity, synthetic yield, and PL quantum yield (PLQY). Additionally, electron transfer between the CDs-IPM, hexavalent chromium (Cr(vi)), and subsequent ascorbic acid (AA) succeeded in turning the fluorescence on and off. The detection limit was 17 nM for Cr(vi), while it was 103 nM for AA. Our study data can simplify the process of synthesis of CDs utilizing biodegradable starting materials. The probe reported in this study may serve as a valuable addition to the field of environment monitoring by virtue of its enhanced detection sensitivity, high selectivity, and stability.

Identification of prognostic factors and construction of a nomogram for patients with relapse/refractory adult-onset Still's disease.

OBJECTIVES: This study aimed to identify the risk factors for relapse/refractory adult-onset Still's disease (AOSD) and to construct and validate a prognostic nomogram for predicting the individual risk of relapse/refractory disease. METHOD: A total of 174 patients were included in our study. Univariate and multivariate logistic regression analyses were used to identify relapse/refractory-associated factors, which were used to construct nomograms. Receiver operating characteristic (ROC) curve analysis, calibration curves, and decision curve analysis (DCA) were used to assess the predictive ability of the nomograms. RESULTS: Univariate and multivariate logistic analyses showed that age, fever, disease duration, platelet count, serum ferritin level, and erythrocyte sedimentation rate were independent unfavourable factors for relapse/refractory AOSD (p < 0.05). We constructed a 6-factor nomogram based on univariate and multivariate logistic analyses. ROC analysis indicated that the area under the curve of the 6-factor nomogram in the training set and test set was 0.765 and 0.714, respectively. In addition, the calibration curves showed excellent prediction accuracy, and DCA showed superior net benefit in the 6-factor nomograms. Moreover, we evaluated the predictive effectiveness of our nomogram in females and young adults. The results showed that our 6-factor nomogram has the same predictive ability in both subgroups. CONCLUSIONS: Novel nomograms based on clinical characteristics were developed and may be applied to help predict the individual risk of poor prognosis of patients. Key Points • Logistic regression was used to identify risk factors for relapse/refractory adult-onset Still's disease. • We then constructed a nomogram for predicting disease risk. • ROC analysis, calibration curves, and DCA all showed that the nomogram exerted good prediction ability in both the training set and test set. • The nomogram has the same predictive ability in both female and young adult subgroups.

The pathogenesis and treatment in antineutrophil cytoplasmic antibody associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a systemic autoimmune disease characterized by leukocytoclastic inflammation of small blood vessels. Commonly detected autoantibodies include anti-protease 3 (PR3) and anti-myeloperoxidase (MPO). Although cell necrosis plays an important role in the production of autoantibodies and the pathogenesis of AAV, the correlation between their titers and disease activity remains elusive. As improved detection techniques facilitate early diagnosis, a satisfactory efficacy can be achieved in patients with mild to medium severe AAV treated with glucocorticoids and immunosuppressants. However, resistant and relapsing AAV, sometimes life-threatening, do exist in clinical practice. In-depth understanding of pathogenesis of AAV may lend novel insight into the mechanism responsible for its formation and help find effective targeted therapies for refractory patients.

Fabrication and Characteristics of Heavily Fe-Doped LiNbO3/Si Heterojunction.

A series of heavily Fe-doped LiNbO3 (LN:Fe) crystals were grown via the Czochralski method. The dark- and photo-conductivity of the 5.0 wt.% Fe-doped LiNbO3 crystal reached 3.30 × 10-8 Ω-1 cm-1 and 1.46 × 10-7 Ω-1 cm-1 at 473 nm, which are about 7 and 5 orders of magnitude higher than that of congruent LiNbO3, respectively. Then, a p-n heterojunction was fabricated by depositing the heavily Fe-doped LiNbO3 on a p-type Si substrate using the pulsed laser deposition. The current-voltage curve of the LN:Fe/Si heterojunction presents a well-defined behavior with a turn-on voltage of 2.9 V. This LN:Fe/Si heterojunction gives an excellent prototype device for integrated optics and electro-photonics.

FoxO3a inhibiting expression of EPS8 to prevent progression of NSCLC: A new negative loop of EGFR signaling.

BACKGROUND: The resistance to EGF receptor (EGFR) tyrosine kinase inhibitors (TKI) is a major challenge in the treatment of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms behind resistance is therefore an important issue. Here we assessed the role of EGFR pathway substrate 8 (EPS8) and Forkhead box O 3a (FoxO3a) as potentially valuable targets in the resistance of NSCLC . METHODS: The expression levels of EPS8 and FoxO3a in patients with NSCLC (n = 75) were examined by immunohistochemistry staining, while in cells were detected by qPCR and western blot. The effects of EPS8 and FoxO3a on resistance, migration and invasion, cell cycle arrest were detected by MTT, transwell and flow cytometry, respectively. Chromatin immunoprecipitation and luciferase reporter assays were performed to determine the mechanisms of EPS8 expression and FoxO3a regulation. FINDINGS: We observed that the expression of EPS8 inversely correlated with FoxO3a in NSCLC cell lines and NSCLC patients. FoxO3a levels were significantly decreased in tumor tissues compared with para-carcinoma tissues, while EPS8 is opposite. Besides, they play reverse roles in the resistance to gefitinib, the migration and invasion abilities, the cell cycle arrest in vitro and the tumor growth in vivo. Mechanistically, FoxO3a inhibits EPS8 levels by directly binding its gene promoter and they form a negative loop in EGFR pathway. INTERPRETATION: Targeting FoxO3a and EPS8 in EGFR signaling pathway prevents the progression of NSCLC, which implied that the negative loop they formed could served as a therapeutic target for overcoming resistance in NSCLC. FUNDS: National Natural Science Foundation of China, Science and Technology Project of Henan, Outstanding Young Talent Research Fund of Zhengzhou University and the National Scholarship Fund.