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Huafeng Wang,1,* Benyan Zhang,1,* Xue Wang,1,* Jianhua Mao,2 Weiguang Li,3 Yunwei Sun,3 Yaozong Yuan,3 Qiwen Ben,3 Li Hua,4 Aihua Qian3 1Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Gastroenterology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Aihua Qian; Li Hua Email qianaihua1981@126.com; seyhuali@163.comPurpose: Transient receptor potential vanilloid 4 (TRPV4) has been reported to be involved in the progression of several human tumors. Nevertheless, clinical significance and molecular mechanism of TRPV4 in gastric cancer (GC) remain poorly defined.Patients and Methods: Immunohistochemistry assays were used to investigate the correlation between the expression of TRPV4 and epithelial–mesenchymal transition (EMT) markers in human GC tissues. The correlations between TRPV4 expression and clinicopathological features and between TRPV4 expression and survival rates were also examined. TRPV4 knockdown was performed by using small interfering RNAs. In vitro, Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and transwell assay were employed to further explore the biological functions of TRPV4, and Western blotting was used to evaluate the changes in the expression of TRPV4 protein and EMT-related proteins in HGC-27 and MGC-803 human GC cell lines.Results: TRPV4 expression was upregulated in GC tissues and cell lines. TRPV4 overexpression was associated with greater depth of tumor invasion, lymph node metastasis, higher TNM stage, poor overall survival, and worse disease-free survival. TRPV4 expression was inversely correlated with E-cadherin expression and positively correlated with vimentin expression. In vitro, knockdown of TRPV4 inhibited GC cell proliferation, colony formation, and invasion. Furthermore, the knockdown of TRPV4 modulated EMT by upregulating E-cadherin expression and downregulating the expression of N-cadherin and vimentin. In addition, the EMT-related transcription factor Snail was downregulated, whereas the expression levels of other transcription factors such as Slug and Twist did not change.Conclusion: TRPV4 was upregulated in human GC and the overexpression of TRPV4 could promote GC progression, partially through Snail-mediated EMT.Keywords: TRPV4, gastric cancer, epithelial–mesenchymal transition, metastasis, prognosis

Aim A world-wide recognised and accepted definition and classification of gastroesophageal reflux disease (GERD) would be highly desirable for research and clinical practice. The purpose of this project was to develop such a generally accepted definition and classification that could be used equally by patients, physicians, and supervisory bodies. Methods In order to ensure a consensus among the participating experts a modified delphi process with a step-wise selection modality was employed. For this the working group of five persons formulated a series of statements on the basis of a systematic search of the literature using three databases (Embase, Cochrane-Study register, Medline). Then these statements were developed further for two years, revised and finally passed as consensus. The consensus group consisted of 44 experts from 18 countries. Each key vote was held on the basis of a six-point scale. A "consensus" was considered to have been reached when two-thirds of the participants voted in favour of the respective statement. Results The level of agreement between the experts increased in the course of the multistep decision process, in the individual voting steps requiring at least two-thirds of the participants, the results were at first 86%, then 88% through to 94% and finally 100% in favour of the chosen statement. In the final voting, 94% of the final 51 statements were accepted by 90% of the consensus group. 90% of all statements were accepted unanimously or with only minor reservations. GERD was defined as a disease that is associated with troublesome symptoms and/or complications on account of reflux of stomach contents into the esophagus. The complaints are divided into esophageal and extra-esophageal syndromes. Among the novel aspects of this definition are the patient-orientated approach that is independent of endoscopic findings, the classification of the ailment into independent syndromes as well as the consideration of laryngitis, cough, asthma and dental problems as possible GERD syndromes. Furthermore, a new definition of suspected or demonstrated Barrett's esophagus is proposed. Conclusion Irrespective of country-specific differences in terminology, language, prevalence and manifestations of this disease, evidence-based, world-wide valid consensus definitions are possible. A global consensus definition of GERD will simplify disease management, make mutual research possible and help in the design of generally valid studies. This will not only help the patient but also the physician and supervisory bodies.