Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chem...Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.展开更多
近年来,在相关政策的加持下,我国农村电子商务取得了前所未有的发展。然而,受农业生产环境、技术条件、基础设施等限制,农村电子商务的发展仍然面临一些困境。加上经历了网络泡沫的寒冬,电子商务现已进入理性时代,缺乏创新的传统电商模...近年来,在相关政策的加持下,我国农村电子商务取得了前所未有的发展。然而,受农业生产环境、技术条件、基础设施等限制,农村电子商务的发展仍然面临一些困境。加上经历了网络泡沫的寒冬,电子商务现已进入理性时代,缺乏创新的传统电商模式已不能满足消费者需求,将面临被淘汰的境遇。因此,农村电子商务需要寻求新的商业模式和营销模式。F2O (Focus to online)是一种新兴的将焦点事件与电子商务结合的电商模式,对于解决农村电子商务发展困境具有启发性作用。基于此,本文结合4R营销理论从关联策略、反应策略、关系策略、回报策略探讨了F2O模式在农村电子商务中的应用。In recent years, with the support of relevant policies, rural e-commerce in our country has achieved unprecedented development. However, due to the limitations of agricultural production environment, technical conditions, and infrastructure, the development of rural e-commerce still faces some difficulties. Coupled with the cold winter of the Internet bubble, e-commerce has entered the rational era, and the traditional e-commerce model that lacks innovation can no longer meet the needs of consumers and will face the situation of being eliminated. Therefore, rural e-commerce needs to seek new business models and marketing models. F2O (Focus to online) is an emerging e-commerce model that combines focus events with e-commerce, which is enlightening to solve the dilemma of rural e-commerce development. Based on this, this paper discusses the application of F2O model in rural e-commerce from the relevancy strategy, reaction strategy, relation strategy and reward strategy combined with 4R marketing theory.展开更多
基金National Yang Ming Chiao Tung University Far Eastern Memorial Hospital Joint Research Programs(NYCU-FEMH 109DN03,110DN06,111DN04,112DN05).
文摘Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.
文摘近年来,在相关政策的加持下,我国农村电子商务取得了前所未有的发展。然而,受农业生产环境、技术条件、基础设施等限制,农村电子商务的发展仍然面临一些困境。加上经历了网络泡沫的寒冬,电子商务现已进入理性时代,缺乏创新的传统电商模式已不能满足消费者需求,将面临被淘汰的境遇。因此,农村电子商务需要寻求新的商业模式和营销模式。F2O (Focus to online)是一种新兴的将焦点事件与电子商务结合的电商模式,对于解决农村电子商务发展困境具有启发性作用。基于此,本文结合4R营销理论从关联策略、反应策略、关系策略、回报策略探讨了F2O模式在农村电子商务中的应用。In recent years, with the support of relevant policies, rural e-commerce in our country has achieved unprecedented development. However, due to the limitations of agricultural production environment, technical conditions, and infrastructure, the development of rural e-commerce still faces some difficulties. Coupled with the cold winter of the Internet bubble, e-commerce has entered the rational era, and the traditional e-commerce model that lacks innovation can no longer meet the needs of consumers and will face the situation of being eliminated. Therefore, rural e-commerce needs to seek new business models and marketing models. F2O (Focus to online) is an emerging e-commerce model that combines focus events with e-commerce, which is enlightening to solve the dilemma of rural e-commerce development. Based on this, this paper discusses the application of F2O model in rural e-commerce from the relevancy strategy, reaction strategy, relation strategy and reward strategy combined with 4R marketing theory.
