The human UGT2B17 gene varies in copy number from zero to two per individual and also differs in mean number between populations from Africa, Europe, and East Asia. We show that such a high degree of geographical variation is unusual and investigate its evolutionary history. This required first reinterpreting the reference sequence in this region of the genome, which is misassembled from the two different alleles separated by an artifactual gap. A corrected assembly identifies the polymorphism as a 117 kb deletion arising by nonallelic homologous recombination between approximately 4.9 kb segmental duplications and allows the deletion breakpoint to be identified. We resequenced approximately 12 kb of DNA spanning the breakpoint in 91 humans from three HapMap and one extended HapMap populations and one chimpanzee. Diversity was unusually high and the time to the most recent common ancestor was estimated at approximately 2.4 or approximately 3.0 million years by two different methods, with evidence of balancing selection in Europe. In contrast, diversity was low in East Asia where a single haplotype predominated, suggesting positive selection for the deletion in this part of the world.

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BackgroundHemostasis in thyroid surgery is of utmost importance for a successful surgery and an uneventful postoperative course. Our aim was to evaluate the effectiveness of the FOCUS Harmonic Scalpel in patients undergoing open total thyroidectomy.MethodsIn this study, 778 patients were randomized into 2 groups based on the surgical technique used: group I comprised the conventional clamp-and-tie technique, group II comprised patients in whom the FOCUS Harmonic Scalpel was used exclusively. The groups were compared in regard to surgical time, complications, and hospital stay.ResultsSurgical time was significantly lower in group II compared with group I (79 ± 21.5 min vs.125 ± 30.4, respectively, P < 0.001). Twenty-seven patients (6.94%) in group I experienced symptomatic hypocalcemia requiring calcium and/or vitamin D therapy versus 14 patients (3.6%) in group II, with statistically significant difference (P < 0.05). Mean post-operative hospital stay was significantly lower in group II compared with group I (2.6 ± 0.9 vs. 2.9 ± 1.0; P < 0.001).ConclusionsThe FOCUS Harmonic Scalpel can shorten operative time and hospital stay, reduce incidence of symptomatic hypocalcemia but not transient hypoparathyroidism, and show no significance on recurrent nerve injury. FOCUS Harmonic Scalpel is supposed to be a more reliable and safe instrument that can take place of the clamp-and-tie technique in total thyroidectomy.

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Laparoscopic primary closure of the CBD is safe and successful for the management of CBD stones. Application of IOC and choledochoscopy to ensure clearance of the CBD and careful suturing are essential for primary closure.

Sorafenib resistance is one of the major obstacles towards achieving a better outcome in patients with advanced hepatocellular carcinoma (HCC), in which aberrant activation of the hepatocyte growth factor (HGF)/mesenchymal‐epithelial transition pathway is frequently observed. Here, we report that HCC cells develop sorafenib resistance following HGF stimulation. Furthermore, HGF activates the downstream extracellular signal‐related kinase (ERK) and signal transducer and activator of transcription 3 (STAT3) pathway and induces epithelial–mesenchymal transition (EMT) by up‐regulating Snail in HCC cells. Inhibition of ERK and STAT3 abolished the rescue effect of HGF by down‐regulating Snail and EMT. Moreover, phosphoinositide 3‐kinase/Akt was also activated in HGF‐treated HCC cells, although it had no effect on Snail expression. Notably, we also found that regorafenib reversed HGF‐induced sorafenib resistance by inhibiting ERK and STAT3, and subsequently down‐regulating Snail and EMT. Taken together, our results indicate that HGF induces sorafenib resistance by activating phosporylated (P)‐ERK/Snail/EMT and P‐STAT3/Snail/EMT pathways. Inhibition of P‐ERK and P‐STAT3 by regorafenib can block HGF‐induced EMT, thereby reversing HGF‐induced sorafenib resistance.

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