Objective:To study the clinicopathologic characteristics and relevant factors affecting prognosis of patients with synchronous bilateral breast cancer.Methods:The clinical data, pathologic characteristics and immunohistochemical expression characteristics of 151 patients with synchronous bilateral breast cancers diagnosed in Peking Union Medical College Hospital from 2008 to 2018 were collected and analyzed. The factors affecting the prognosis were analyzed by Log rank test, Kaplan-Meier survival analysis, Cox regression and other methods.Results:Synchronous bilateral breast cancer cases accounted for 1.2% (151/12 239) of all breast cancer patients in the same period, and 14.6% (22/151) had a family history. The patients′ age range was 22-88 years, mainly female, with a mean survival of 42.5 months. There were 106 patients with synchronous bilateral invasive breast cancers, 6 patients with synchronous bilateral breast cancer in situ, and 39 patients with unilateral invasive breast cancer and unilateral breast cancer in situ. In synchronous bilateral invasive breast cancers, the histological type was mainly non-specific type (84.9%, 180/212), the histological grade was mainly Grade 2 (60.8%,129/212), the TNM stage was mainly stage Ⅰ (50.5%, 107/212), the tumor size was mainly T1 (68.9%, 146/212), and the regional lymph node was mainly N0 (61.8%, 131/212). The molecular subtypes were mainly Luminal A-like (38.1%, 75/197) and Luminal B-like (43.7%, 86/197); ER (78.2%, 154/197) and PR (72.1%,142/197)were mainly positive, and HER2 was mainly negative (91.9%, 181/197). There were 85 (80.2%) patients and 75 (70.8%) patients with the same histological type and histological grade on both sides, respectively. The concordance of tumor size T stage and the regional lymph nodes N stage were 58.5% (62/106) and 55.7% (59/106), respectively. The concordance of molecular subtype was 54.9% (50/91), and the concordance of ER, PR, HER2 and Ki-67 were 83.5% (76/91), 76.9% (70/91), 89.0% (81/91) and 59.3% (54/91), respectively. The expression of ER and PR in synchronous bilateral invasive breast cancer was significantly correlated with prognosis ( P<0.05). Conclusions:Among patients with synchronous bilateral breast cancers, bilateral invasive breast cancer is the most common, the prognosis is the worst, and the pathologic characteristics of bilateral breast cancer tend to be consistent. The expression of ER and PR in synchronous bilateral invasive breast cancer is significantly correlated with prognosis, that is, best for bilateral ER-positive patients, worst for bilateral ER-negative patients, and intermediate for unilateral ER-positive patients, thus suggesting the importance of ER and PR detection in synchronous bilateral invasive breast cancers.

Objective:To investigate the clinicopathological features and differential diagnosis of metastatic tumors in the lung.Methods:The clinicopathological data of 226 metastatic tumors in the lung were collected at Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, from January 2014 to December 2018, and the pathomorphological characteristics were analyzed.Results:There were 84 males and 142 females, with an age range from 13 to 77 years. There were 122 patients with multiple pulmonary nodules and 104 patients with solitary pulmonary nodule. The tumors of the highest frequencies were colorectal cancer ( n=59), followed by trophoblast tumor ( n=44), kidney cancer ( n=31), breast cancer ( n=20), cervix cancer ( n=14), and urinary urothelium cancer ( n=8). The time from the diagnosis of primary tumors to metastasis and the status of surgical treatment varied by tumor origin. The morphology of metastatic lung tumors overlapped with that of the primary tumors to some extent. The relative specific morphological characteristics and the presence of carcinoma in situ surrounding the tumors should be carefully searched for to confirm the tumor origin. The metastatic tumors of the lung had morphological characteristics, immunohistochemical TTF1 (-) and tumor of various sources, while the primary tumor differentiation had relatively specific antibodies: colorectal cancer CK20 (+), CDX2 (+), CK7 (-); malignant trophoblastic tumor, HCG (+); renal clear cell carcinoma CD10 (+), vimentin (+), CK7 (-); breast cancer, GATA3 and ER (+); cervical cancer, p16 (+); urothelial carcinoma, CK20, p63 and GATA3 (+). Conclusions:There is overlap between pulmonary metastatic tumor and primary tumor in morphology. Therefore, the diagnosis should be made by combining clinical history, pathological morphology and immunophenotypic characteristics.

Classic hypothalamic-pituitary-end-organ feedback loops – the hypothalamic-pituitary-adrenal axis (HPAA), hypothalamic-pituitary-thyroidal axis (HPTA), and hypothalamic-pituitary-gonadal axis (HPGA) – are associated with the neuroendocrine and immune systems in major depressive disorder (MDD). Female patients with MDD present with evident neuroendocrine and immunological changes. Glucocorticoid, thyroid hormone, and reproductive steroid levels fluctuate with menstrual cycles, which might lead to glucocorticoid receptor resistance, impairment of triiodothyronine conversion, and sex hormone secretion disorders. In this review, we summarize the independent and interactive functions of these three axes in female MDD patients. The similar molecular structure of steroids implies an interrelationship between the hypothalamic-pituitary-end-organ axes and the competitive inhibitory effects at the receptor level, especially when considering the HPAA and HPGA.

Neuroimmune system may be involved in the pathological process of bipolar disorder (BD), but the essential association is not fully understood. Accumulating evidence has shown that BD involves the activation of immune cells and the release of inflammatory substances in the central nerve system (CNS). Meanwhile, neuroimmune responses also interact with other hypothesis of the etiology of BD that are widely recognized, such as neurotransmitter systems, neuroendocrine systems, neurotrophic factors, and oxidative stress. Simultaneously, related genes and immune changes in peripheral blood vary with it. Overall, neuroimmunity may play an important role in the pathogenesis of BD, and the inflammatory cytokines, especially interleukin-6 and tumor necrosis factor-alpha, have potential value for the clinical diagnosis and prognosis of BD, as well as predicting the therapeutic effects of drugs. Large-scale studies are needed to extend the evidence on neuroimmunity in BD, and to examine its clinical value for applications such as early prediction and treatment.

Early distinction of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools are available to estimate the risk of BD. In this study, we aimed to develop and validate a model of oxidative stress injury for predicting BD. Data were collected from 1252 BD and 1359 MDD patients, including 64 MDD patients identified as converting to BD from 2009 through 2018. 30 variables from a randomly-selected subsample of 1827 (70%) patients were used to develop the model, including age, sex, oxidative stress markers (uric acid, bilirubin, albumin, and prealbumin), sex hormones, cytokines, thyroid and liver function, and glycolipid metabolism. Univariate analyses and the Least Absolute Shrinkage and Selection Operator were applied for data dimension reduction and variable selection. Multivariable logistic regression was used to construct a model for predicting bipolar disorder by oxidative stress biomarkers (BIOS) on a nomogram. Internal validation was assessed in the remaining 784 patients (30%), and independent external validation was done with data from 3797 matched patients from five other hospitals in China. 10 predictors, mainly oxidative stress markers, were shown on the nomogram. The BIOS model showed good discrimination in the training sample, with an AUC of 75.1% (95% CI: 72.9%-77.3%), sensitivity of 0.66, and specificity of 0.73. The discrimination was good both in internal validation (AUC 72.1%, 68.6%-75.6%) and external validation (AUC 65.7%, 63.9%-67.5%). In this study, we developed a nomogram centered on oxidative stress injury, which could help in the individualized prediction of BD. For better real-world practice, a set of measurements, especially on oxidative stress markers, should be emphasized using big data in psychiatry.
Biomarkers/metabolism* ; Bipolar Disorder/metabolism* ; Depressive Disorder, Major/diagnosis* ; Early Diagnosis ; Humans ; Oxidative Stress