Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-alpha or polyethylene glycol (PEG)-interferon-alpha alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been advanced to clinical trials in human beings for the treatment of hepatitis C viral infections is described. X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed.

Out of the breast cancer subtypes, triple-negative breast cancer (TNBC) has the poorest prognosis without effective targeted therapies. Metformin, a first-line drug for type 2 diabetes mellitus, was demonstrated to target breast cancer stem cells selectively. However, the efficiency and the mechanism of action of metformin in TNBC are unclear. In this study, we demonstrated that metformin decreased the percentage of TNBC stem cells partially through the downregulation of the expression of the stem cell transcription factor Krüppel-like factor 5 (KLF5) and its downstream target genes, such as Nanog and FGF-BP1, in TNBC cell lines. Metformin induced glycogen synthase kinase-3β (GSK3β)-mediated KLF5 protein phosphorylation and degradation through the inhibition of protein kinase A (PKA) activity in TNBC cells. Consistently, PKA activators increased the expression levels of KLF5. We observed a positive correlation between p-CREB, p-GSK3β, KLF5 and FGF-BP1 protein levels in human TNBC samples. These findings suggest that metformin suppresses TNBC stem cells partially through the PKA-GSK3β-KLF5 signaling pathway.

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RPD is more efficient and secure process than LPD among properly selected patients. RPD is therefore a feasible alternative to the laparoscopic procedure. Further studies are needed to evaluate the cost effectiveness of the robotic approach for PD.

RDP is associated with less rate of conversion to laparotomy, shorter PHS, and improved SP and SVP rates in selected patients than LDP.

Simultaneously acquiring chemical and topographical information within asingle cell at nanoscale resolutions is vital to cellular biology,yet it remains agreat challenge due to limited lateral resolutions and detection sensitivities.H erein, the development of near-field desorption mass spectrometry for correlated chemical and topographical imaging is reported, therebyb ridging the gap between laser-based mass spectrometry (MS) methods and multimodal single-cell imaging.Using this integrated platform, an imaging resolution of 250 nm and 3D topographically reconstructed chemical single-cell imaging were achieved.T his technique offers more in-depth cellular information than micrometer-range laser-based MS imaging methods.C onsidering the simplicity and compact sizeo ft he near-field device,this techniquecan be introduced to MALDI-MS,e xpanding the multimodal abilities of MS at nanoscale resolutions.

Background: Robotic surgery is increasingly being used in hepatectomy. Previous studies comparing the robotic and laparoscopic minor hepatectomy have been documented, but comparative studies on robotic and laparoscopic hemihepatectomy (LH) involving a large patient cohort are rare. The objective of this study was to compare perioperative outcomes between robotic and LH.Methods: Data on the demographics, clinicopathologic characteristics, and perioperative outcomes of consecutive patients who underwent robotic or LH in a single center between November 2011 and July 2017 were analyzed.Results: A total of 92 patients underwent robotic and 48 LH. Multiple linear regression analysis showed no significant difference in perioperative outcomes including operative time, postoperative hospital stay, postoperative complications, and mortality between the groups. Compared to the laparoscopic cohort, the robotic cohort had a significantly less estimated blood loss (120.24 mL; 95% confidence interval, 53.72-186.76) and a significantly lower conversation rate (1.09% vs 10.42%; P = .034). Stratified and interaction analyses demonstrated that disease type had an interaction effect on the association between the operative approach and the estimated blood loss.Conclusions: Robotic hemihepatectomy was safe and feasible in selected patients.It had similar perioperative outcomes as LH and was better than LH regarding estimated blood loss and open conversion.

Laparoscopic surgery is a safe procedure for patients with benign insulinomas. The complication rates are comparable with those for laparotomy procedures. Relative to open operations, laparoscopic pancreas operations are associated with a more rapid postoperative recovery.