IGF2BP1 and cancer / 国际肿瘤学杂志

The insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is a key regulator of mRNA metabolism and transport during development. Recent studies indicate that IGF2BP1 is aberrantly expressed in liver cancer, lung cancer, colon cancer, ovarion cancer, breast cancer, etc.. IGF2BP1 expression is found to promote tumor cell proliferation, migration, invasion, and correlate with poor prognosis. Further understanding of the mechanism of IGF2BP1 in malignancy may provide new targeted therapy strategies.

miR-885-5p inhibits proliferation and metastasis by targeting IGF2BP1 and GALNT3 in human intrahepatic cholangiocarcinoma.

The incidence of intrahepatic cholangiocarcinoma (iCCA) continues to increase worldwide, however its molecular pathogenesis remains poorly understood. Recent studies have implicated microRNAs in iCCA progression. In this study, we demonstrated that miR-885-5p was significantly decreased in iCCA tissues. Downregulation of miR-885-5p was correlated with vascular invasion, lymph node metastasis, unfavorable overall survival, and shorter disease-free survival. Silencing or overexpressing miR-885-5p by lentiviral approaches significantly influenced iCCA cell proliferation and metastasis in vitro and in vivo. Mechanistically, overexpression of miR-885-5p inhibited iCCA metastasis and proliferation by directly inhibiting GALNT3 as well as by indirectly promoting the downregulation of insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1). Furthermore, miR-885-5p inhibited iCCA metastasis by downregulating the PI3K/AKT/MMPs signaling pathway via targeting GALNT3. Collectively, we demonstrated that miR-885-5p was an important mediator of iCCA proliferation and metastasis by regulating GALNT3 and IGF2BP1, thus offering a potential target for iCCA treatment.

Dysregulation of the miR-148a-GLUT1 axis promotes the progression and chemoresistance of human intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a highly fatal malignant cancer worldwide. Elucidating the underlying molecular mechanism of iCCA progression is critical for the identification of new therapeutic targets. The present study explored the role of the miR-148a-GLUT1 axis in the progression of iCCA. The expression of GLUT1 was detected by using immunohistochemistry, western blot assays, and real-time polymerase chain reaction. The effects of GLUT1 on cell proliferation, invasion, and chemoresistance were investigated both in vitro and in vivo. A luciferase reporter assay was used to explore the effect of miR-148a on GLUT1 expression. GLUT1 was overexpressed in iCCA tissues. GLUT1 overexpression was associated with shorter overall and disease-free survival. Knockdown of GLUT1 reduced, while overexpression of GLUT1 promoted, the proliferation, motility, and invasiveness of iCCA cells in vitro and in vivo. Silencing GLUT1 significantly sensitized iCCA cells to gemcitabine in vitro and in vivo. GLUT1 was directly regulated by miR-148a, whose downregulation was associated with the proliferation, migration, and invasion of iCCA cells. WZB117, a GLUT1 inhibitor, inhibited tumor growth in an iCCA patient-derived xenograft model. These results indicate that downregulation of miR-148a levels results in GLUT1 overexpression in iCCA, leading to iCCA progression and gemcitabine resistance.

MUC13 promotes intrahepatic cholangiocarcinoma progression via EGFR/PI3K/AKT pathways.

BACKGROUND & AIMS: Mucin 13 (MUC13) is reportedly overexpressed in human malignancies. However, the clinicopathological and biological significance of MUC13 in human intrahepatic cholangiocarcinoma (iCCA) remain unclear. The aim of this study was to define the role of MUC13 in the progression of iCCA. METHODS: Expression levels of MUC13 in human iCCA samples were evaluated by immunohistochemistry, western blot, and real-time PCR. In vitro and in vivo experiments were used to assess the effect of MUC13 on iCCA cell growth and metastasis. Crosstalk between MUC13 and EGFR/PI3K/AKT signaling was analyzed by molecular methods. The upstream regulatory effects of MUC13 were evaluated by Luciferase and DNA methylation assays. RESULTS: MUC13 was overexpressed in human iCCA specimens and iCCA cells. MUC13 overexpression positively correlated with clinicopathological characteristics of iCCA, such as vascular invasion and lymph node metastasis, and was independently associated with poor survival. Results from loss-of-function and gain-of-function experiments suggested that knockdown of MUC13 attenuated, while overexpression of MUC13 enhanced, the proliferation, motility, and invasiveness of iCCA cells in vitro and in vivo. Mechanistically, we found that the phosphatidylinositol 3-kinase-AKT signal pathway and its downstream effectors, such as tissue inhibitor of metalloproteinases 1 and matrix metallopeptidase 9, were required for MUC13-mediated tumor metastasis of iCCA. MUC13 interacted with epidermal growth factor receptor (EGFR) and subsequently activated the EGFR/PI3K/AKT signaling pathway by promoting EGFR dimerization and preventing EGFR internalization. We also found that MUC13 was directly regulated by miR-212-3p, whose downregulation was related to aberrant CpG hypermethylation in the promoter area. CONCLUSIONS: These findings suggest that aberrant hypermethylation-induced downregulation of miR-212-3p results in overexpression of MUC13 in iCCA, leading to metastasis via activation of the EGFR/PI3K/AKT signaling pathway. LAY SUMMARY: Mucin 13 overexpression has been implicated in the development of malignancies, although its role in intrahepatic cholangiocarcinoma has not been studied. Herein, we show that mucin 13 plays a critical role in intrahepatic cholangiocarcinoma. Mucin 13 could have therapeutic value both as a prognostic marker and as a treatment target.

Exploration of SPOC-based mixed teaching mode in the teaching of general surgery / 中华医学教育探索杂志

In response to the teaching requirements under the new situation of medical education reform, the Department of General Surgery of the First Affiliated Hospital of Harbin Medical University has actively carried out the SPOC (small private online course). Through special seminars, online platform exchanges and skill operation exercises, students can accurately grasp the learning focus and learn the subject knowledge efficiently, which has realized the teaching goals of situational, problematic, multi-dimensional and task-based teaching and learning. It is a new type of online and offline interactive teaching model, which is worth further promotion.

Application of medical virtual simulation experimental teaching platform in general surgery teaching / 中华医学教育探索杂志

Medical virtual simulation experimental teaching platform has the characteristics of high openness and sharing, overcoming resource constraints, diversified teaching methods and so on. Applying the virtual simulation platform to general surgery teaching, students can break through the constraints of the textbooks, and perform immersive practical operations on the network by watching experimental videos, and simulating virtual instrument, and experimental materials online, so as to improve their hands-on skills and increase their interest in learning.

Practical exploration of MOOC teaching in general surgery teaching / 中华医学教育探索杂志

This study apply MOOC graduate student in general surgery teaching , with the help of the teaching video quality , flexible learning time , video miniaturization unique advantages , such as students can choose the time and place, through online resource sharing, test evaluation and simulation of the virtual patient, positive interaction with teachers classmates on the Internet, so that the students can study more efficiently and master course knowledge . Studies have shown that students' average scores have improved and their overall scores have also improved . In future teaching , MOOC can be combined with traditional teaching to complement each other's advantages .

Ertapenem for the treatment of bacterial liver abscess / 中华普通外科杂志

ObjectiveTo explore the efficacy of an antibiotic ertapenem for the treatment of bacterial liver abscess. MethodThe clinical data of 134 hospitalized bacterial liver abscess patients were retrospectively analyzed to evaluate the clinical and bacteriological efficacy of ertapenem from March 2009-2011in our hospital. ResultFever was present in 122 (91％)cases,abdominal pain was complained in 70 (52.2％ ) cases and rigor in 66 (49.3％ ) cases.In 92(68.7％ ) cases the abscess was located in the right lobe of the liver.Leukocytosis and liver dysfunction were found in 73 cases(54.8％ ) and 84 cases (62.7％ ),respectively.Ultrasonography was the most effective diagnostic means for liver abscess.Fortyone cases(30.6％ )were treated conservatively with ertapenem and 82(61.2％ )were treated with ertapenem associated with percutaneous liver puncture aspiration and 11cases (8.2％ )were treated with ertapenem associated with surgery.The clinical success rate was respectively 89％,87.8％,90.9％.The average duration of medication and length of stay were respectively ( 7.0 ± 2.4 ) d and 14.2 d.Ninety-seven pathogens were isolated from samples and predominant strains were Klebsiella species.Bacterial eradication rate was 92.8％.The sensitivities of isolated bacteria to ertapenem were 94.8％.ConclusionsErtapenem administration is effective therapy for bacterial liver abscess.

A multi-centric randomized controlled trial of sequential intravenous moxifloxacin in comparison to cefoperazone-sulbactam for the treatment of acute biliary tract infection / 中华普通外科杂志

ObjectiveTo compare the efficacy and safety of sequential intravenous moxifloxacin treatment against cefoperazone/sulbactam in patients with acute biliary tract infection. MethodsA prospective, randomized, non-blind, multi-centric study was performed to compare the efficacy and safety of moxifloxacin 400 mg Ⅳ once daily to cefoperazone-sulbactam (2 g q12 hours) and metronidazole 250 ml once daily to treat patients, from March- December 2009 in 13 hospitals, with acute biliary tract infection.The primary efficacy variable was clinical cure rate after the end of a 5 - 14 day treatment period,bacteriologic outcomes and adverse reaction effects were also determined.ResultsA total of 319 subjects were enrolled, 282 of whom were eligible for protocol efficacy analyses ( 138 moxifloxacin, 144 comparator).Demographic and baseline medical characteristics were similar between the 2 groups. Clinical success rates were 86.2％ for moxifloxacin and 84. 7％ for the comparator(P =0. 7192). Pathogens (55 moxifloxacin, 61 comparator) were isolated from bile or blood cultures and the predominant strains were E. coli, Klebsiella species and Enterococcus species. Bacterial eradication rates were 85.4％ ( 37 of 55 ) with moxifloxacin versus 82. 0％ (50 of 61 ) in the comparator group ( x2 = 0. 2568, P = 0. 6123 ). Both treatments were safe and well tolerated. ConclusionsE. coli, Klebsiella species and Enterococcus species were the most common bacteria isolated from bile or blood from patients with acute biliary tract infection. Moxifloxacin monotherapy has high clinical and bacteriological efficacies and safety for the treatment of acute biliary tract infection.