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5 in NMSA. It also suggested that AKAP5 might potentially have biological functions in the development of stomach adenocarcinoma. 2020 Annals of Translational Medicine. All rights reserved.Background The tumor microenvironment (TME) is critical to every aspect of cancer biology. NSC 362856 purchase Organotypic tumor slice cultures (TSCs) preserve the original TME and have demonstrated utility in predicting drug sensitivity, but the association between clinicopathologic parameters and in vitro TSC behavior has not been well-defined. Methods One hundred and eight fresh tumor specimens from liver resections at a tertiary academic center were procured and precisely cut with a Vibratome to create 250 μm × 6 mm slices. These fixed-dimension TSCs were grown on polytetrafluoroethylene inserts, and their metabolic activities were determined by a colorimetric assay. Correlation between baseline activities and clinicopathologic parameters was assessed. Tissue CEA mRNA expression was determined by RNAseq. Results By standardizing the dimensions of a slice, we found that adjacent tumor slices have equivalent metabolic activities, while those derived from different tumors exhibit >30-fold range in baseline MTS absorbances, which correlated significantly with the percentage of tumor necrosis based on histologic assessment. Extending this to individual cancers, we were able to detect intra-tumoral heterogeneity over a span of a few millimeters, which reflects differences in tumor cell density and Ki-67 positivity. For colorectal cancers, tissue CEA expression based on RNAseq of tumor slices was found to correlate with clinical response to chemotherapies. Conclusions We report a standardized method to assess and compare human cancer growth ex vivo across a wide spectrum of tumor samples. TSC reflects the state of tumor behavior and heterogeneity, thus providing a simple approach to study of human cancers with an intact TME. 2020 Annals of Translational Medicine. All rights reserved.Background Growth differentiation factor 15 (GDF15) has already been reported as a novel efficient biomarker in patients with coronary artery diseases (CAD). However, very little is demonstrated about the potential impact of pericardial fluid GDF-15 accumulation on CAD. The aim of this study was to evaluate pericardial fluid and plasma GDF15 levels in patients with ischemic heart disease. Methods In this study, 42 consecutive patients (21 patients with significant CAD; 21 patients without CAD) undergoing open heart surgery were recruited in this study. Pericardial fluid were obtained at the time of surgery, and GDF15 levels in the samples were measured by enzyme-linked immunosorbent assay. Plasma glucose, creatinine, CK-MB, cTnI and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements were performed. Results The plasma GDF15 levels were markedly higher than the pericardial fluid levels both in the CAD group and non-CAD group (1,174.0±148.7 vs. 677.8±77.2 pg/mL, P0.05). An obvious correlation wasonal Medicine. All rights reserved.Background To investigate the etiology of urinary tract and respiratory infections and the rate of drug resistant bacteria in Shanghai from 2015 to 2017, provide the support to the promotion of the correct clinical etiological specimens detection. link2 Methods The retrospective questionnaire survey was conducted to obtain the antibiotic prescription rate, pathogen detection rate, and isolation rate of drug-resistant bacteria of the inpatients in 66 hospitals of Shanghai in 2015 and 2017. Results Although the detection rate of multidrug-resistant bacteria in sputum specimens has decreased, the clinical pathogen detection still relied mainly on sputum specimens in 2017. Among the sputum specis, the detection rates of extended-spectrum β-lactamase-producing Escherichia (ESBL-ESC), extended-spectrum β-lactamase Klebsiella pneumoniae (ESBL-KP), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and methicillin-resistant Staphylococcus aureus (MRSA) in 2017 were 66.67%, 32.46%, 61.74%, 32.01% and 58.55% respectively. The detection rates of ESBL-ESC, ESBL-KP, CRAB, CRPA in 2017 were increased while the MRSA was decreased than 2015 (P less then 0.001). Among the blood samples, the detection rates of ESBL-ESC, ESBL-KP, CRAB, CRPA, MRSA and vancomycin-resistant Enterococcus sp (VRE) in 2017 were 53.71%, 31.43%, 50.80%, 19.43%, 43.87% and 0.55% respectively. The detection rates of ESBL-KP, CRAB, CRPA and MRSA increased while the rates of ESBL-ESC and VRE decreased compared with 2015 (P less then 0.005). The pathogens of multi-drug resistant bacteria were mainly detected from sputum specimens in 2017, which were all higher than detected from the blood specimens (P less then 0.001). Conclusions Most of the multi-drug resistant bacteria in Shanghai, especially in Acinetobacter baumannii or Pseudomonas aeruginosa are mainly detected from sputum specimens, indicating that the actual drug resistance may be overestimated. 2020 Annals of Translational Medicine. All rights reserved.Background With recommendation of surgical management in primary site, both the positive and negative lymph nodes (LNs) retrieved have been emphasized to predict prognosis in stage IV rectum cancer. Therefore, we attempt to compare the prognostic performance of American Joint Committee on Cancer (AJCC) N-stage relative to lymph node ratio (LNR), log odds of metastatic lymph nodes (LODDS), and N-score in stage IV rectal cancer. Methods Total 5,090 patients taken surgical resection of primary site in rectum cancer with distant metastasis were extracted from Surveillance, Epidemiology, and End Results Program (SEER) database. Harrell's C statistic (C-index) and Akaike's Information Criterion (AIC) were used to evaluate the discriminative ability of the different LN staging systems. Results Of the 3,243 patients without radiotherapy, 82.46% (n=2,675) had been found with lymph nodes metastasis with median number of 16 lymph nodes collected (IQR 11-22). Modeled as categorical cutoff variables for further clinical uod discriminative ability and goodness of fit in predicting survival for stage IV rectum cancer patients regardless of radiation therapy status. 2020 Annals of Translational Medicine. All rights reserved.Background Pectus excavatum (PE), one of the most common congenital chest wall deformities, is characterized by posterior depression of the sternum and lower costal cartilages. In this study, we demonstrated the application of flexible three-dimensional printing thoracic models for surgical approach planning of extrapleural Nuss procedure for patients with pectus excavatum. Methods Six patients with pectus excavatum were referred to our hospital for extrapleural Nuss procedure. Each patient's chest was reconstructed based on their computed tomography imaging data, and the three-dimensional (3D) thoracic model was manufactured with flexible material using 3D printing technique. The individual surgical approach and custom-made steel bars were designed and produced using these models. Results The surgical approach was evaluated by using the three-dimensional thoracic model. In all patients received extrapleural Nuss surgery, it has been proven the uniformity of repair efficacy in both models and patients. Moreover, an individualized and well-fitting steel bar can be fabricated once the surgical approach was confirmed. All the steel bars were loaded against the ribs rigorously and seamlessly. Conclusions The flexible three-dimensional thoracic models were very helpful for the preoperative planning of extrapleural Nuss procedure. 2020 Annals of Translational Medicine. All rights reserved.Background Liver metastases are the most common cause of death for patients with colorectal cancer and affect up to half of the patients. Liver resection is an established method that can potentially be curative. For patients with extrahepatic disease (EHD), the role of liver surgery is less established. Methods This is a retrospective study based on data from the national quality registry SweLiv. Data were obtained between 2009 and 2015. SweLiv is a validated registry and has been in use since 2009, with coverage above 95%. Patients with liver metastases and EHD were analyzed and cross-checked against the national death cause registry for survival analysis. Results During the study period, 2,174 patients underwent surgery for colorectal liver metastases (CRLM), and 277 patients with EHD were treated with resection or ablation. The estimated median survival time for the entire cohort from liver resection/ablation was 40 months (95% CI, 32-47). The survival time for patients treated with liver resection was 45 months compared to 26 months for patients treated with ablation (95% CI 38-53, 18-33, P=0.001). A subgroup analysis of resected patients revealed that the group with pulmonary metastases had a significantly longer estimated median survival (50 months; 95% CI, 39-60) than the group with lymph node metastases (32 months; 95% CI, 7-58) or peritoneal carcinomatosis (28 months; 95% CI, 14-41) (P=0.022 and 0.012, respectively). Other negative prognostic factors were major liver resection and nonradical liver resection. Conclusions For patients with liver metastases and limited EHD, liver resection results in prolonged survival compared to what can be expected from chemotherapy alone. 2020 Annals of Translational Medicine. All rights reserved.Background To build the triple-negative breast cancer (TNBC) radiation resistance model in vitro and vivo, and screen the molecular markers that related to radiation resistance. Methods We used X-ray to irradiate MDA-MB-231 cells repeatedly to build radioresistant cell (231-RR), then select one gemcitabine-resistance of MDA-MB-231 cell (231-GEM). We screen differentially expressed genes of these cell lines. Then, we would select 2 genes of them associated with DNA damage repair or cell cycle, and build RNAi lentivirus vector to knock down related gene. We also used X-rays repeatedly exposure TNBC tumor xenograft to build tumor with radioresistance properties, and then verify previously screening differentially expressed genes using IHC. Finally, we used The Cancer Genome Atlas (TCGA) database to validate the relationships between radioresistance related genes and the prognosis of breast cancer. Results We got 161 up-regulated genes and 156 down-regulated genes from three cell lines. Cellular results show the on sensitivity. 2020 Annals of Translational Medicine. All rights reserved.Background Forkhead box K1 (FOXK1) is a transcription factor that contributes to cancer development, but it is unclear how FOXK1 regulates the proliferation and migration of gastric cancer (GC) cells. The purpose of this study was to investigate the clinical significance, biological function, and molecular mechanisms of FOXK1 in GC. link3 Methods We conducted bioinformatics assays and western blotting to assess FOXK1 expression. Then, we performed immunohistochemistry (IHC) with tissue microarrays (TMAs) to assess FOXK1 expression in order to identify an association between FOXK1 expression levels and clinical parameters. We used 5-ethynyl-2'-deoxyuridine (EdU), wound healing and Transwell assays to determine whether FOXK1 promotes malignant behaviors in GC. Furthermore, immunofluorescence staining, transmission electron microscopy and western blotting were used to verify an association between FOXK1 and autophagy. Results We observed high levels of FOXK1 expression in GC tissues, which were associated with the degree of malignancy in GC.