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Dianhui Xiu,1 Lin Liu,1 Min Cheng,1 Xiaosong Sun,2 Xibo Ma3 1Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun 130021, Jilin, People’s Republic of China; 2Department of Thyroid-Head and Neck Surgery, Jilin Cancer Hospital, Changchun 130021, Jilin, People’s Republic of China; 3Department of Otolaryngology, Jilin Provincial People’s Hospital, Changchun 130021, Jilin, People’s Republic of ChinaCorrespondence: Lin Liu; Min ChengDepartment of Radiology, China-Japan Union Hospital of Jilin University, No. 126, Sendai Street, Changchun City, Jilin Province, People’s Republic of ChinaEmail uyigtl@163.com; nrwpne@163.comBackground: Prostate cancer (PCa) is a common malignant tumor of the urinary system in males. LncRNA taurine-upregulated gene 1 (TUG1) has been verified to play a crucial role in progression and prognosis of PCa. However, the functional mechanism of TUG1 remains unclear with radiosensitivity of PCa.Methods: Quantitative real-time PCR (qRT-PCR) was conducted to measure the transcription levels of genes. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis were employed to assess cell proliferation and apoptosis, respectively. Moreover, colony formation assay was used to measure colony survival. Western blot was performed to detect the relative proteins expression. The interaction among variables was predicted by online tool starbase, and then confirmed using the dual luciferase reporter assay. A xenograft mouse model was constructed to investigate the effect of TUG1 on tumor growth in vivo.Results: The levels of lncRNA TUG1 and SMC1A were remarkably increased, while miR-139-5p was downregulated in PCa. Patients with high expression of TUG1 showed a lower survival rate and poor prognosis. Knockdown of TUG1 inhibited PCa cell proliferation and colony survival fraction, and promoted apoptosis. Downregulation of miR-139-5p reversed the effects of TUG1 deletion on proliferation, apoptosis and colony survival fraction in PCa cells treated with 4 Gy of X-ray radiation. Moreover, TUG1 sponged miR-139-5p to regulate SMC1A expression. SMC1A deletion blocked the effects of TUG1 on the progression of PCa cells treated with 4 Gy of X-ray radiation. The tumor volume and weight were illustriously reduced with radiation and TUG1 silencing in xenograft model.Conclusion: Knockdown of lncRNA TUG1 enhanced radiosensitivity in PCa via the TUG1/miR-139-5p/SMC1A axis. It may become a promising target for PCa treatment.Keywords: TUG1, miR-139-5p, SMC1A, prostate cancer, radiosensitivity

Meng Lu,1 Dian-rong Xiu,2 Li-mei Guo,3 Chun-hui Yuan,2 Ling-fu Zhang,2 Lian-yuan Tao2 1Department of Pulmonary Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, People’s Republic of China; 2Department of General Surgery, Peking University Third Hospital, Beijing, People’s Republic of China; 3Department of Pathology, Peking University Third Hospital, Beijing, People’s Republic of ChinaCorrespondence: Dian-rong XiuPeking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, People’s Republic of ChinaTel +86 156 1190 8135Email xiudianrong@163.comBackground: Pancreatic ductal adenocarcinoma has a devastatingly poor prognosis, and most prognostic factors reflected the tumor stage more than the tumors’ biology. The peripheral nerve plexus is densely distributed in the tumor micro-environment, and there are interactions between tumor cells and these nerves. Perineural invasion is an important risk factor for tumor recurrence and metastasis in pancreatic head adenocarcinoma, but the concrete types of extrapancreatic neuropathy and its role in predicting prognosis are still not clear.Objective: To clarify the role of extrapancreatic neuropathy in the early postoperative liver metastasis and tumor-related mortality in pancreatic head adenocarcinoma and to study the mechanism of tumor recurrence and liver metastasis in pancreatic head adenocarcinoma.Methods: We reported a retrospective study of 60 patients with resectable pancreatic head adenocarcinoma, all of whom accepted radical pancreaticoduodenectomy. Plexus pancreaticus capitalis II (PLX-II) was the representation of extrapancreatic plexus in our study, and all of these plexus had immunohistochemical staining. We defined the postoperative tumor recurrence and tumor-related mortality within 6 months as the early prognostic indicators and analyzed the pathological alterations in PLX-II among different prognosis groups.Results: There were 18 patients suffering early postoperative liver metastasis; these two groups differed significantly in the average number of nerve trunks (P

Puxian Tang,1,2,* Lianyuan Tao,1,3,* Chunhui Yuan,1 Lingfu Zhang,1 Dianrong Xiu1 1Department of General Surgery, Peking University Third Hospital, Beijing 100191, People’s Republic of China; 2Department of Intensive Care Unit, Beijing Hospital, Beijing 100730, People’s Republic of China; 3Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dianrong XiuDepartment of General Surgery, Peking University Third Hospital, No. 49, Hua Yuan North Road, Hai Dian District, Beijing 100191, People’s Republic of ChinaTel +86-10-82267320Fax +86-10-62010334Email xiudianrong@hotmail.comBackground: Pancreatic cancer (PC) is one of the most aggressive malignancies and has a poor prognosis despite being extensively researched. The role of serum-derived exosomes in tumorigenesis and the development of PC is still unclear.Method: The present study employed iTRAQ-based proteomic analysis to search for differences between the serum exosomes of PC patients and those from control patients. Then, bioinformatics methods were used to analyze the functions of the identified proteins, and the possible functions were verified through cell culture experiments.Results: A total of 611 proteins were identified from exosomes, and 141 proteins were differentially expressed, with 91 up- and 50 down regulated proteins in PC cancer compared to healthy controls. Further analysis indicated that APOE serves as an important hub in the network. In addition, CRP, VWF, APOA2, NIN, and GSK3B potentially interact with many other proteins. We then tested the effect of patient serum-derived exosomes on pancreatic cancer cells and found that patient serum-derived exosomes, but not those from healthy controls, induced cell proliferation, migration, and EMT, supporting the role of exosomes in metastasis.Conclusion: Our data suggest that exosomes derived from PC patients may promote PC metastasis.Keywords: proteomic analysis, pancreatic cancer, serum exosome, metastasis

Lianyuan Tao,1,2 Li Su,3 Chunhui Yuan,1 Zhaolai Ma,1 Lingfu Zhang,1 Shiping Bo,4 Yunyun Niu,4 Sijia Lu,4 Dianrong Xiu11Department of General Surgery, Peking University Third Hospital, Beijing 100191, People’s Republic of China; 2Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, People’s Republic of China; 3Medical and Health Analytical Center, Peking University Health Science Center, Beijing 100191, People’s Republic of China; 4Department of Clinical Research, Yikon Genomics Co. Ltd., Shanghai, People’s Republic of ChinaPurpose: The aim of this study was to evaluate the value of flow cytometry (FCM) detection of portal vein circulating tumor cells (CTCs) in predicting postoperative metastasis.Methods: Samples of portal venous blood and peripheral blood were collected from 39 patients during surgery, and CTCs were detected by FCM, with confirmation by laser confocal microscopy and single-cell sequencing.Results: Among all patients, a portal EpCAM+CD45- percentage ≥24.5×10−4 (P=0.06), peripheral EpCAM+CD45- count ≥97/5 mL (P=0.034), peripheral EpCAM+CD45- percentage ≥4.4×10−4 (P=0.042), and CA242≥3.5U/mL (P=0.027) were significant predictors of metastasis. Further analysis showed that the portal EpCAM+CD45- ratio ≥24.5×10−4 is a predictor of metastasis (P=0.025) in pancreatic cancer after curative resection.Conclusion: CTCs detected by FCM in portal venous blood are of significant value for the prediction of postoperative metastasis in pancreatic or periampullary tumors.Keywords: circulating tumor cells, flow cytometry, portal vein, pancreatic cancer, metastases &nbsp

Ge Gao,1,* Dianhui Xiu,2,* Bin Yang,3 Daju Sun,1 Xin Wei,4 Youpeng Ding,4 Yanan Ma,4 Zhixin Wang4 1Department of Pathology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China; 2Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China; 3Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China; 4Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China *These authors contributed equally to this work Background: Prostate cancer is one of the most commonly diagnosed diseases in males. Methods: RT-qPCR was used to detect miR-129-5p expression in tumor tissues and adjacent normal tissues from patients with prostate cancer. The cell proliferation assay and colony forming assay were used to study the role of miR-129-5p in mediating prostate cancer cell growth. Bioinformatic analysis and dual luciferase assay were performed to predict and confirm ETV1 as a target gene of miR-129-5p. Results: We found that miR-129-5p levels were decreased significantly in human prostate cancer tissues compared with matched normal tissues from patients with prostate cancer. Overexpression of miR-129-5p suppressed prostate cancer cell growth while antagonist of miR-129-5p promoted cell proliferation in immortal prostate cell line RWPE-1. In addition, elevation of miR-129-5p decreased ETV1 expression in prostate cancer cells while downregulation of miR-129-5p increased ETV1 expression in RWPE-1. Mechanistically, ETV1 is confirmed a direct target of miR-129-5p in prostate cancer cells. Through repression of ETV1 expression, miR-129-5p could inactivate YAP signaling in prostate cancer cells. In addition, overexpression of ETV1 attenuated miR-129-5p induced cell proliferation in prostate cancer cells. Correlation analysis further revealed that there was a negative correlation between miR-129-5p levels and ETV1 mRNA levels in tumor tissues from patients with prostate cancer. Conclusion: Our results identified miR-129-5p as a tumor suppressor in prostate cancer via repression of ETV1. Keywords: microRNA, prostate cancer, ETV1, proliferation

Lingfu Zhang,1 Lianyuan Tao,1 Limei Guo,2 Jun Zhan,3 Chunhui Yuan,1 Zhaolai Ma,1 Bin Jiang,1 Dianrong Xiu1 1Department of General Surgery, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Pathology, Peking University Third Hospital, Beijing, People’s Republic of China; 3Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing, People’s Republic of China Background: Recent studies demonstrated that granulocyte colony-stimulating factor (G-CSF), regularly used for the prevention of neutropenia, is engaged in cancer progression. However, the role of G-CSF in pancreatic ductal adenocarcinoma (PDAC) is not clear. The aim of the present study was to investigate the expression and prognostic value of G-CSF in patients with PDAC.Materials and methods: The localization and expression of G-CSF in PDAC were examined by immunohistochemistry (IHC). The analysis of the levels of G-CSF in plasma was evaluated using ELISA kit. The correlation between G-CSF expression and patients’ survival was assessed by Kaplan–Meier analysis.Results: In IHC specimens, G-CSF was discovered predominantly in the cell cytoplasm and expressed in most of PDAC, while in plasma, the systemic level of G-CSF is no different between normal patients and pancreatic cancer patients. In 100 PDAC cases with IHC, patients with grades 2 and 3 were defined as the high expression group (41 patients, 41%), and those with grades 0 and 1 as the low expression group (59 patients, 59%). Significant correlation was noted between high G-CSF expression and neural invasion (P = 0.042) or early recurrence (P&nbsp

Wendi Li, Lianyuan Tao, Lingfu Zhang, Dianrong Xiu Department of General Surgery, Peking University Third Hospital, Beijing, China Background: Lymphocyte to monocyte ratio (LMR) was recently reported as a prognostic factor of pancreatic cancer (PC). However, the prognostic role of LMR in PC remains inconsistent and inconclusive. The aim of this study was to assess the prognostic value of LMR in patients with PC through meta-analysis.Methods: Eligible studies inquiring into the connection between LMR and survival of patients with PC were collected and extracted by searching PubMed, Embase, Cochrane Library and Web of Science up to May 9, 2017. Pooled hazard ratios (HRs) and the 95% CIs were calculated to assess the prognostic value of LMR on overall survival (OS) and disease-free survival/recurrence-free survival/time to progression (DFS/RFS/TTP).Results: A total of 1,795 patients with PC from 8 studies were included in the meta-analysis. Pooled analysis indicated that elevated LMR predicted a favorable OS (HR=0.56, 95% CI: 0.38–0.83, P=0.004) and DFS/RFS/TTP in PC patients (HR=0.38, 95% CI: 0.15–0.95, P=0.04). Prognostic values of LMR on OS were observed in subgroups with all ethnicities, treatment with surgery, American Joint Committee on Cancer (AJCC) stage of III–IV, and LMR cut-off value ≥3. In addition, low LMR was significantly connected with gender and AJCC stage.Conclusion: An elevated LMR is associated with favorable survival in patients with pancreatic cancer. Keywords: pancreatic cancer, lymphocyte to monocyte ratio (LMR), meta-analysis, prognosis

We report the influence of surface morphology and charge of alginate/chitosan (ACA) microcapsules on both the amount of adsorbed protein and its secondary structural changes during adsorption. Variations in surface morphology and charge were controlled by varying alginate molecular weight and chitosan concentration. Plasma fibrinogen (Fgn) was chosen to model this adsorption to foreign surfaces. The surface of ACA microcapsules exhibited a granular structure after incubating calcium alginate beads with chitosan solution to form membranes. The surface roughness of ACA microcapsule membranes decreased with decreasing alginate molecular weight and chitosan concentration. Zeta potential measurements showed that there was a net negative charge on the surface of ACA microcapsules which decreased with decreasing alginate molecular weight and chitosan concentration. The increase in both surface roughness and zeta potential resulted in an increase in the amount of Fgn adsorbed. Moreover, the higher the zeta potential was, the stronger the protein-surface interaction between fibrinogen and ACA microcapsules was. More protein molecules adsorbed spread and had a greater conformational change on rougher surfaces for more surfaces being available for protein to attach.

Catechol-O-methyltransferase (COMT) Val158Met (rs4680) polymorphism plays a crucial role in regulating brain dopamine level. Converging evidence from Caucasian samples showed that, compared with rs4680 Val allele, the Met allele was linked to lower COMT activity, which in turn was linked to better cognitive performance such as working memory (WM) and to a larger hippocampus (a brain region important for WM). However, some behavioral studies have shown that the function of rs4680 appears to vary across different ethnic groups, with Chinese subjects showing an opposite pattern as that for Caucasians (i.e. the Val allele is linked to better cognitive functions related to WM in Chinese). Using a sample of healthy Han Chinese college students (ages from 19 to 21years), this study investigated the association of COMT Val158Met genotype with behavioral data on a two-back WM task (n = 443, 189M/254F) and T1 MRI data (n=320, 134M/186F). Results showed that, compared to the Met allele, the Val allele was associated with larger hippocampal volume (the right hippocampus: β = -0.118, t = -2.367, P = 0.019, and the left hippocampus: β = -0.099, t = -1.949, P = 0.052) and better WM performance (β = -0.110, t = -2.315, P = 0.021). These results add to the growing literature on differentiated effects of COMT rs4680 polymorphism on WM across populations and offer a brain structural mechanism for such population-specific genetic effects. © 2013 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

The chemical modification of the alginate/chitosan/alginate (ACA) hydrogel microcapsule with methoxy poly(ethylene glycol) (MPEG) was investigated to reduce nonspecific protein adsorption and improve biocompatibility in vivo. The graft copolymer chitosan-g-MPEG (CS-g-MPEG) was synthesized, and then alginate/chitosan/alginate/CS-g-MPEG (ACAC(PEG)) multilayer hydrogel microcapsules were fabricated by the layer-by-layer (LBL) polyelectrolyte self-assembly method. A quantitative study of the modification was carried out by the gel permeation chromatography (GPC) technique, and protein adsorption on the modified microcapsules was also investigated. The results showed that the apparent graft density of the MPEG side chain on the microcapsules decreased with increases in the degree of substitution (DS) and the MPEG chain length. During the binding process, the apparent graft density of CS-g-MPEG showed rapid growth-plateau-rapid growth behavior. CS-g-MPEG was not only bound to the surface but also penetrated a certain depth into the microcapsule membranes. The copolymers that penetrated the microcapsules made a smaller contribution to protein repulsion than did the copolymers on the surfaces of the microcapsules. The protein repulsion ability decreased with the increase in DS from 7 to 29% with the same chain length of MPEG 2K. CS-g-MPEG with MPEG 2K was more effective at protein repulsion than CS-g-MPEG with MPEG 550, having a similar DS below 20%. In this study, the microcapsules modified with CS-g-MPEG2K-DS7% had the lowest IgG adsorption of 3.0 ± 0.6 μg/cm(2), a reduction of 61% compared to that on the chitosan surface.

Contains fulltext : 240328.pdf (Author’s version preprint ) (Open Access) In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in sample estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: non-standard errors. To study them, we let 164 teams test six hypotheses on the same sample. We find that non-standard errors are sizeable, on par with standard errors. Their size (i) co-varies only weakly with team merits, reproducibility, or peer rating, (ii) declines significantly after peer-feedback, and (iii) is underestimated by participants. 31 mei 2023