Single-Cell Sequencing of Malignant Ascites Reveals Transcriptomic Remodeling of the Tumor Microenvironment during the Progression of Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) is the main cause of mortality among gynecological malignancies worldwide. Although patients with EOC undergo aggregate treatment, the prognosis is often poor. Peritoneal malignant ascites is a distinguishable clinical feature in EOC patients and plays a pivotal role in tumor progression and recurrence. The mechanisms of the tumor microenvironment (TME) in ascites in the regulation of tumor progression need to be explored. We comprehensively analyzed the transcriptomes of 4680 single cells from five EOC patients (three diagnostic samples and two recurrent samples) derived from Gene Expression Omnibus (GEO) databases. Batch effects between different samples were removed using an unsupervised deep embedding single-cell cluster algorithm. Subcluster analysis identified the different phenotypes of cells. The transition of a malignant cell state was confirmed using pseudotime analysis. The landscape of TME in malignant ascites was profiled during EOC progression. The transformation of epithelial cancer cells into mesenchymal cells was observed to lead to the emergence of related anti-chemotherapy and immune escape phenotypes. We found the activation of multiple biological pathways with the transition of tumor-associated macrophages and fibroblasts, and we identified the infiltration of CD4+CD25+ T regulatory cells in recurrent samples. The cell adhesion molecules mediated by integrin might be associated with the formation of the tumorsphere. Our study provides novel insights into the remodeling of the TME heterogeneity in malignant ascites during EOC progression, which provides evidence for identifying novel therapeutic targets and promotes the development of ovarian cancer treatment.

Impacts of six potential HONO sources on HOx budgets and SOA formation during a wintertime heavy haze period in the North China Plain.

The Weather Research and Forecasting/Chemistry (WRF-Chem) model updated with six potential HONO sources (i.e., traffic, soil, biomass burning and indoor emissions, and heterogeneous reactions on aerosol and ground surfaces) was used to quantify the impact of the six potential HONO sources on the production and loss rates of OH and HO2 radicals and the concentrations of secondary organic aerosol (SOA) in the Beijing-Tianjin-Heibei (BTH) region of China during a winter heavy haze period of Nov. 29-Dec. 3, 2017. The updated WRF-Chem model well simulated the observed HONO concentrations at the Wangdu site, especially in the daytime, and well reproduced the observed diurnal variations of regional-mean O3 in the BTH region. The traffic emission source was an important HONO source during nighttime but not significant during daytime, heterogeneous reactions on ground/aerosol surfaces were important during nighttime and daytime. We found that the six potential HONO sources led to a significant enhancement in the dominant production and loss rates of HOx on the wintertime heavy haze and nonhaze days (particularly on the heavy haze day), an enhancement of 5-25 µg m-3 (75-200%) in the ground SOA in the studied heavy haze event, and an enhancement of 2-15 µg m-3 in the meridional-mean SOA on the heavy haze day, demonstrating that the six potential HONO sources accelerate the HOx cycles and aggravate haze events. HONO was the key precursor of primary OH in the BTH region in the studied wintertime period, and the photolysis of HONO produced a daytime mean OH production rate of 2.59 ppb h-1 on the heavy haze day, much higher than that of 0.58 ppb h-1 on the nonhaze day. Anthropogenic SOA dominated in the BTH region in the studied wintertime period, and its main precursors were xylenes (42%), BIGENE (31%) and toluene (21%).

Primary small-cell neuroendocrine carcinoma of the urinary bladder: A rare case and a review of the literature.

Primary small-cell neuroendocrine carcinoma (SCNEC) of the urinary bladder is a rare tumor characterized by poor differentiation and high aggressiveness. Only ~150 cases have been reported in the literature to date. We herein present a case of an 87-year-old man who presented with hematuria and was found to have an ill-defined mass in the urinary bladder on computed tomography and cystoscopic examination. On pathological examination following tumor biopsy, the mucosa of the bladder wall was found to be extensively infiltrated by neuroendocrine carcinoma, positive for CD56 and synaptophysin and negative for epithelial membrane antigen, consistent with SCNEC of the urinary bladder. The patient refused further surgical treatment and succumbed to the disease 2 months after the diagnosis. In the present study, this rare case of primary SCNEC of the urinary bladder is presented, along with a discussion on the clinical presentation, immunohistochemical and cytomorphological characteristics, management, biological behavior and prognosis of this disease.

Correlation between epidermal growth factor receptor mutation and histologic subtypes or characteristics of computed tomography findings in patients with resected pulmonary adenocarcinoma.

OBJECTIVE: To investigate the correlation between epidermal growth factor receptor (EGFR) mutation and the histologic subtypes features or computed tomography (CT) findings in patients with resected pulmonary adenocarcinoma. MATERIALS AND METHODS: We retrospectively reviewed 153 patients underwent surgical resected pulmonary adenocarcinoma. EGFR mutations were detected using the amplification refractory mutation system. Histologic subtype was classified according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society pulmonary adenocarcinoma classification. Characteristics of CT in the tumor were retrospectively analyzed, and compared to mutation-negative cohort. RESULTS: EGFR mutations were found in 67 (43.79%) cases. The prevalent histologic subtypes of invasive adenocarcinoma were acinar predominant adenocarcinoma (33.99%), papillary predominant adenocarcinoma (24.18%), micropapillary predominant adenocarcinoma (MPA; 18.95%), solid predominant adenocarcinoma (11.76%), and lepidic predominant adenocarcinoma (LPA; 11.11%). EGFR mutations were correlated with the MPA and LPA subtypes (P = 0.009 and P = 0.018) and was correlated with the air bronchograms (P = 0.008). EGFR mutations were independently associated with other CT characteristics including ground-glass opacity/tumor ratio (P = 0.054). CONCLUSIONS: Correlation exists between EGFR mutations and histologic subtypes of invasive adenocarcinoma or air bronchograms on CT images, which could use to predict EGFR mutation status in patients with pulmonary adenocarcinoma.