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// Ying-Chen Xu 1 , Chao-Jie Liang 1 , Dong-Xin Zhang 1 , Guan-Qun Li 1 , Xia Gao 1 , Jian-Zhu Fu 1 , Feng Xia 1 , Jia-Jun Ji 1 , Li-Jun Zhang 1 , Guang-Ming Li 1 and Ji-Xiang Wu 1 1 Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China Correspondence to: Ji-Xiang Wu, email: sflian2001@163.com Guang-Ming Li, email: cya_wl556@163.com Keywords: HCC, lncSHRG, SATB1, HES6, proliferation Received: March 21, 2017 Accepted: July 12, 2017 Published: August 03, 2017 ABSTRACT Hepatocellular carcinoma, one of the most common cancers, leads to mass mortality worldwide currently. However, the underlying mechanism of its oncogenesis remains to be elucidated. Here we identified that a long noncoding RNA, lncSHRG , was greatly upregulated in human hepatocellular carcinoma samples. We found that lncSHRG was essential for liver cancer cell proliferation and tumor propagation in mice. In mechanism, lncSHRG recruits SATB1 to bind to HES6 promoter and initiates HES6 expression. HES6, which is highly expressed in hepatocellular carcinoma, promotes tumor cell proliferation. High expression level of HES6 is positively correlated with clinical severity and poor prognosis of people with hepatocellular carcinoma. Altogether, our research provides a new insight on the mechanism of hepatocellular carcinoma progression.

Introduction: Choledocholithiasis is usually treated with endoscopic sphincterotomy (EST), laparoscopic common bile duct exploration (CBDE) (LCBDE), or laparoscopic transcystic CBDE (LTCBDE). However, the comparative long-term prognosis of these methods in terms of adverse outcomes remains uncertain. Methods: In an ambispective, multicenter, observational, open cohort study, patients with cholecystocholedocholithiasis underwent one of three treatments (EST+laparoscopic cholecystectomy (LC), LCBDE+LC, and LTCBDE+LC).The primary outcome was adverse outcomes. Results: At a median follow-up period of 2.72 years among 2708 patients, the adverse outcome rate is 9.3%. Compared with LCBDE and LTCBDE groups, EST group displayed an increased risk for adverse outcomes (HR 1.25, 95% CI 0.93-1.69, P=0.146; HR 1.77, 95% CI 1.30-2.43, P

Angiogenesis and JAK2 V617F mutation are common in BCR-ABL1 negative myeloproliferative neoplasms (MPNs). Ruxolitinib, a JAK inhibitor, is an effective treatment for some MPNs. However, the relationship between angiogenesis and JAK2 V617F and the effects of ruxolitinib on angiogenesis are still unknown. Here, we observed the correlation of JAK2 V617F mutation burden with VEGF, HIF-1a and microvascular density (MVD) in MPNs. We investigate the effect of ruxolitinib on the expression of VEGF and HIF-1α in JAK2 V617F positive cells. We found the expression levels of p-JAK2, VEGF, HIF-1a and MVD in the newly diagnosed MPNs were significantly increased and were related to the JAK2 V617F burden. Ruxolitinib can inhibit p-JAK2, VEGF, HIF-1a expression and suppress blood vessels’ formation in chick embryo choriallantoic membrane. Our findings indicated that angiogenesis is related to JAK2 V617F burden and ruxolitinib could decrease VEGF and HIF-1a expression in JAK2 V617F positive cells.

To research the suppressive effect of interferon α2b (IFN-α2b) on angiogenesis of JAK2 tyrosine kinase gene point mutation (JAK2V617F) positive myeloproliferative neoplasm (MPN) and its anti-angiogenic mechanisms.(1) A total of 42 cases of JAK2V617F positive MPN patients in the No.1 Hospital of Baoding were selected between January 2012 and October 2014, including the newly diagnosed group before treatment (n=25) and the IFN-α2b treatment group (n=17). Ten cases of idiopathic immune thrombocytopenic purpura (ITP) patients were enrolled as controls. JAK2V617F/JAK2 ratio was detected by real-time fluorescent quantitative PCR to measure mutation; the expression levels of phosphorylated JAK2 (p-JAK2), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α) and CD105 marked microvascular density (MVD) in bone marrow were detected by immunohistochemistry. The correlations were analyzed among JAK2V617F mutation burden and VEGF, HIF-1α, and MVD. (2) Human erythroleukemia cell line HEL cells were treated with different concentrations of IFN-α2b. The apoptosis was detected by Hoechst staining method. The cell viability was detected by CCK-8 test. Cell migration ability was tested by transwell chambers. The protein expression levels of p-JAK2, VEGF, and HIF-1α were detected by Western blot.(1)The ratio of JAK2V617F/JAK2 in the IFN-α2b treatment group (22.69% ± 12.64%) was significantly lower than that in the newly diagnosed group (46.17% ± 19.32%) (P0.01). The expression levels of p-JAK2, VEGF, and HIF-1α in the newly diagnosed group (82.41% ± 11.65%, 64.72% ± 25.01%, 45.12% ± 20.28%) were significantly higher than those in the IFN-α2b treatment group (60.93% ± 20.57%, 36.58% ± 15.95%, 32.15% ± 14.27%) and the control group (43.05% ± 12.59%, 25.69%± 1 3.75%, 25.07% ± 15.49%) (all P0.01). MVD in the newly diagnosed group (26.58% ± 5.93%) was significantly higher than that in the treatment group (15.86%± 4.27%) and the control group (10.76% ± 4.01%) (P0.01). Spearman correlation analysis showed positive correlation of JAK2V617F mutation with VEGF and MVD (r=0.589, P0.05; r=0.577, P0.05). (2)The apoptosis of HEL cells were increased after treated with 30 000 U/L of IFN-α2b in HEL cells after 24 h. The proliferation of HEL cell were inhibited by different concentrations of IFN-α2b in time- and dose-dependent manner. The number of membrane-permeating HEL cells after treated with 5 000 U/L of IFN-α2b in HEL cells after 24 h was significantly lower than that in the untreated cells (52.9 ± 7.5 vs 77.3 ± 6.1) (P0.05). The expression levels of p-JAK2, VEGF, and HIF-1α were decreased in a dose-dependent manner.IFN-α2b may exert an anti-angiogenic effect by inhibiting the VEGF, HIF-1α, and MVD expression in MPN via JAK2 signal pathway.

Ischemic preconditioning (IPC) protects liver graft function following ischemia in liver transplantation and liver resection. The aim of this study was to assess the advantages and any potential disadvantages of liver IPC prior to isolation for rat hepatocytes during isolation and cryopreservation. After isolating and thawing the cryopreserved hepatocytes after 14 and 28 d, cell viability, efficiency, and lactate dehydrogenase (LDH) levels in preserve solution were examined for every group. Groups treated with IPC had better cell viability determination, assessment of plating efficiency and lactate dehydrogenase (LDH) assay than Group without IPC, suggesting that IPC prior to isolation may have a significant protective effect on hepatocytes subjected to isolation and short period cryopreservation.