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        Regulatory Mechanism of MicroRNA-145 in the Pathogenesis of Acute Aortic Dissection

        Tianbo Li,Chencheng Liu,Lingchao Liu,Han Xia,Yingbin Xiao,Xuefeng Wang,Yong Wang 연세대학교의과대학 2019 Yonsei medical journal Vol.60 No.4

        Purpose: Previous studies have confirmed that microRNAs play important roles in the pathogenesis of acute aortic dissection(AAD). Here, we aimed to explore the role of miR-145 and its regulatory mechanism in the pathogenesis of AAD. Materials and Methods: AAD tissue samples were harvested from patients with aortic dissection and normal donors. Rat aorticvascular smooth muscle cells (VSMCs) were transfected with miR-145 mimic/inhibitor or negative control mimic/inhibitor. Geneand protein expression was measured in human aortic dissection tissue specimens and VSMCs by qRT-PCR and Western blot. Luciferasereporter assay was applied to verify whether connective tissue growth factor (CTGF) was a direct target of miR-145 inVSMCs. Methyl thiazolyl tetrazolium assay was used to detect VSMC viability. Results: miR-145 expression was downregulated in aortic dissection tissues and was associated with the survival of patients withAAD. Overexpression of miR-145 promoted VSMC proliferation and inhibited cell apoptosis. Moreover, CTGF, which was increasedin aortic dissection tissues, was decreased by miR-145 mimic and increased by miR-145 inhibitor. Furthermore, CTGF wasconfirmed as a target of miR-145 and could reverse the promotion effect of miR-145 on the progression of AAD. Conclusion: miR-145 suppressed the progression of AAD by targeting CTGF, suggesting that a miR-145/CTGF axis may provide apotential therapeutic target for AAD.

      • Single Purse-String Duct to Mucosa Pancreaticogastrostomy: A New Technique after Pancreaticoduodenectomy

        ( Xu’ An Wang ),( Ping Wang ),( Yingbin Liu ),( Shuyou Peng ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

        Aims: We developed a new technique termed the single purse-string duct to mucosa Pancreaticogastrostomy, which reduced the risk of pancreatic stump bleeding caused by gastric acid corrosion and decreased the pancreatic fistula rate than Pancreaticojejunostomy. Methods: Data were collected prospectively on 75 consecutive patients (43 men and 32 women; mean age 65.3 years who underwent pancreaticoduodenectomy using the single-string duct to mucosa Pancreaticogastrostomy. The technique was performed by the same surgeon and the key point is that pancreatic stump was placed between gastric mucosa and seromuscular layer.Pancreatic stump was covered with gastric mucosa and transfixed with it beside the pancreatic duct which was inserted with a silicone tube into the stomach lumen. finally, the gastric seromuscular layer was tied with the pancreas by a purse-string suture. Results: Mean time for PG anastomosis was 19 minutes (range 17 to 32 minutes), and mean blood loss was 380 mL (range 210 to 800 mL). There was no perioperative death. Over- all morbidity rate was 34.7% (26 of 75).Two patients had PF (overall rate was 2.7%) ,No one demonstrated a grade B or C postoperative PF.Postoperative abdominal hemorrhage developed in 2 patients (2.7%), no pancreatic stump bleeding occurs. Conclusions: These results suggest that our technique is effective. In addition to lower complication rates, this technique is easy to perform and mean time of the anastomosis was 19 minutes. This kind anastomosis is a reliable, safe, and easy to perform method. From our experiences, it appears to reduce the risk for pancreatic fistula and intragastric bleeding.

      • ERBB Signaling Pathway Targeted Therapy Is Available in Gallbladder Cancer Patients

        ( Xu’an Wang ),( Maolan Li ),( Xiangsong Wu ),( Ping Dong ),( Wei Gong ),( Yingbin Liu ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

        Aims: To profile the somatic mutation spectrum in gallbladder cancers(GBCs), to determine the oncogenic effects of the ERBB3 and ERBB2 mutations, and to find whether targeted therapy focus on ERBB signaling pathway is available for these kind of GBC patients. Methods: We performed a combination of exome sequencing and ultra-deep sequencing of cancer-related genes on 57 tumor-normal pairs. The mutation pattern is defined by a dominant prevalence of C>T mutations at TCN sites.Three patients with staged IV GBCs and ERBB signaling pathway mutated who were not benefit from traditional chemo-radio therapy, were treated with ERBB signaling pathway targeted therapy. Results: Genes with a significant frequency of non-silent mutations include TP53 (47.1%), KRAS (7.8%) and ERBB3 (11.8%). Moreover, ErbB signaling (including EGFR, ERBB2, ERBB3, ERBB4 and their downstream genes), which have not been described previously in GBC, is the most extensively mutated pathway, affecting 36.8% (21/57) of the GBC samples. Multivariate analyses further show that the mutations have a worse outcome. Over-expression of each ERBB mutant resulted in a significant increase in proliferation in at least one cell line.The tumor maker expression including CA-199 and CA-125 had a different level of decline.The primary or metastasis tumor size also revealed a trend of decrease. And the average survival time have exceeded more than 12months. Conclusions: Our findings provide insight into the somatic mutational landscape in GBC and highlight the key role of the ErbB signaling pathway in GBC pathogenesis.And our results suggest that patients harboring mutations in the ErbB pathway might benefit from targeted therapies.

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