Breast cancer is the second leading cause of cancer death in women. Serum biomarkers such as cancer antigen 15-3 (CA15-3), cancer antigen 125 (CA125), and carcinoembryonic antigen (CEA) can be used as diagnostic and prognostic factors and can also provide valuable information during follow-up. However, serum protein biomarkers show limited diagnostic sensitivity and specificity in stand-alone assays because their levels reflect tumor burden. To validate whether biomarkers in nipple discharge may serve as novel biomarkers for breast cancer, we composed a panel of potential cancer biomarkers, including CA15-3, CA125, CEA, and malignant tumor-specific growth factor (TSGF), and evaluated their expression in both serum and nipple discharge in order to explore the expression and significance of estrogen receptor (ER), progestrone receptor (PR), epidermal growth factor receptor type 2 (HER2/neu), CA15-3, CA125, CEA, and TSGF expression for their combined predictive value for breast cancer and in judging the prognosis of breast cancer. Univariate analysis revealed that combined detection of CA15-3, CA125, CEA, and TSGF in nipple discharge served as novel biomarkers for the diagnosis and prognosis of breast cancer, but in the multivariate analyses the adverse effects of the four biomarkers combination in nipple discharge positivity on overall survival were lost. Multivariate analysis revealed that the positivity of the combined detection of the four biomarkers in both nipple discharge and serum was significantly higher than that of other detection methods. Thus, the combined detection of these four biomarkers both in serum and nipple discharge was retained as an independent prognostic variable in breast cancer patients. Our results indicate that CA15-3, CA125, CEA, and TSGF in nipple discharge can serve as novel biomarkers in the diagnosis and prognosis of breast cancer.

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Objects: Effective psychological function requires that cognition is not affected by task-irrelevant emotional stimuli in emotional conflict. Depression is mainly characterized as an emotional disorder. The object of this study is to reveal the behavioral and electrophysiological signature of emotional conflict processing in major depressive disorder (MDD) using event-related potentials (ERPs) and standardized low-resolution brain electromagnetic tomography (sLORETA) analysis.Method: We used a face–word Stroop task involving emotional faces while recording EEG (electroencephalography) in 20 patients with MDD and 20 healthy controls (HCs). And then ERPs were extracted and the corresponding brain sources were reconstructed using sLORETA.Results: Behaviorally, subjects with MDDs manifested significantly increased Stroop effect when examining the RT difference between happy incongruent trials and happy congruent trials, compared with HC subjects. ERP results exhibited that MDDs were characterized by the attenuated difference between P300 amplitude to sad congruent stimuli and sad incongruent stimuli, as electrophysiological evidence of impaired conflict processing in subjects with MDD. The sLORETA results showed that MDD patients had a higher current density in rostral anterior cingulate cortex (rostral ACC) within N450 time window in response to happy incongruent trials than happy congruent stimuli. Moreover, HC subjects had stronger activity in right inferior frontal gyrus (rIFG) region in response to incongruent stimuli than congruent stimuli, revealing successful inhibition of emotional distraction in HCs, which was absent in MDDs.Conclusion: Our results indicated that rostral ACC was implicated in the processing of negative emotional distraction in MDDs, as well as impaired inhibition of task-irrelevant emotional stimuli, relative to HCs. This work furnishes novel behavioral and neurophysiological evidence that are closely related to emotional conflict among MDD patients.

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