Neuroendocrine tumors of the gallbladder(GB-NET) are rare, and it lacks early clinical manifestations and has no specific tumor markers, it is difficult to distinguish GB-NET from gallbladder adenocarcinoma. The diagnosis of GB-NET is based on histopathology of the tumor and the assessment of proliferation fraction, which makes it difficult to achieve early diagnosis. GB-NET has a high degree of malignancy, 32.39% of patients have liver metastases at diagnosis, and 51.60% of patients have lymph node metastases, the median survival time is 9 to 10 months.There are currently no specific guidelines or consensus for the treatment of GB-NET. The treatment strategies are choosen mainly by the principles of gallbladder adenocarcinoma. We reviews the clinical and basic researches of GB-NET and case reports from China and across the world, as well as the data from SEER database, and we discuss the research progress on the classification, clinicopathological features, diagnosis, treatment advances and the prognosis.

Genistein and its monoglucoside derivatives play important roles in food and pharmaceuticals fields, whereas their applications are limited by the low water solubility. Glycosylation is regarded as one of the effective approaches to improve water solubility. In this paper, the glycosylation of sophoricoside (genistein monoglucoside) was investigated using a cyclodextrin glucosyltransferase from Penibacillus macerans (PmCGTase). Saturation mutagenesis of D182 from PmCGTase was carried out. Compared with the wild-type (WT), the variant D182C showed a 13.42% higher conversion ratio. Moreover, the main products sophoricoside monoglucoside, sophoricoside diglucoside, and sophoricoside triglucoside of the variant D182C increased by 39.35%, 56.05% and 64.81% compared with that of the WT, respectively. Enzymatic characterization showed that the enzyme activities (cyclization, hydrolysis, disproportionation) of the variant D182C were higher than that of the WT, and the optimal pH and temperature of the variant D182C were 6 and 40℃, respectively. Kinetics analysis showed the variant D182C has a lower K_m value and a higher k_cat/K_m value than that of the WT, indicating the variant D182C has enhanced affinity to substrate. Structure modeling and docking analysis demonstrated that the improved glycosylation efficiency of the variant D182C may be attributed to the increased interactions between residues and substrate.
Cyclodextrins ; Genistein ; Glucosyltransferases/metabolism* ; Glycosylation ; Kinetics