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The aim of this study is to investigate certain genetic features of intrahepatic cholangiocarcinoma (ICCA). A total of 12 eligible ICCA patients were enrolled, and tumor tissues from the patients were subjected to next-generation sequencing of a multi-genes panel. Tumor mutation burden (TMB), mutated genes, copy number variants (CNVs), and pathway enrichment analysis were performed. The median TMB was 2.76 Mutation/Mb (range, 0-36.62 Mutation/Mb) in ICCA patients. The top two most commonly mutated genes in ICCA were KRAS (33%) and TP53 (25%). The co-mutations of KRAS and TP53 were 16.7% (2/12) in ICCA patients. Notably, patient P6 with the highest TMB did not have KRAS and TP53 mutations. Additionally, TP53 and/or KRAS alterations were significantly associated with poor progression-free survival than those with wild type (1.4 months vs 18 months). DNA damage repair and homologs recombinant repair deficiencies were significantly associated with high TMB in ICCA cases. In conclusion, we found that certain genetic mutations of TP53 and KRAS could predict poor prognosis in ICCA patients.

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Background: Intrahepatic biliary cystadenoma (IBC) is a rare benign cystic tumor of the liver. So far, it has not been comprehensively understood, which causes incorrect diagnosis, treatment confusion, and even inappropriate treatment. Here, we reviewed clinical data of IBC patients in our center, shared our experiences and lessons learned, and improved the level of diagnosis and treatment. Methods: The clinical data of 10 patients with pathologically diagnosed IBC, admitted to the Department of Hepatobiliary Surgery of the Affiliated Hospital of Guangdong Medical University from January, 2007, to January, 2022 were retrospectively analyzed. Results: 10 patients underwent surgery and were discharged successfully. Cyst morphology: multiple cysts: 6 cases (6/10), monocular cyst: four cases(4/10). Six patients (6/10) were diagnosed as IBC preoperatively and received hepatectomy. Four patients with monocular cyst IBC underwent intraoperative frozen section examination, except one case showed IBC; the rest were misdiagnosed as simple liver cyst. In three misdiagnosed patients, one underwent open left hepatectomy seven days after the initial operation. The other patient refused to undergo reoperation and required follow-up observation. The last patient could not tolerate hepatectomy due to insufficient residual liver volume and chose follow-up observation. Conclusion: For IBC, especially monocular IBC, it is easy to be misdiagnosed as simple hepatic cyst, which brings great confusion to clinical treatment. We propose strengthening communication with pathologists to deepen understanding of IBC. Attention should be paid to the cyst wall's shape and the cyst fluid's properties during the operation to avoid the missed diagnosis, misdiagnosis, or even improper operation. For suspicious cases, directly choose hepatectomy to avoid reoperation after thoroughly evaluating the patient's condition.

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Hepatic disease negatively impacts liver function and metabolism. Primary human hepatocytes are the gold standard for the prediction and successful treatment of liver disease. However, the sources of hepatocytes for drug toxicity testing and disease modeling are limited. To overcome this issue, pluripotent stem cells (PSCs) have emerged as an alternative strategy for liver disease therapy. Human PSCs, including embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) can self-renew and give rise to all cells of the body. Human PSCs are attractive cell sources for regenerative medicine, tissue engineering, drug discovery, and developmental studies. Several recent studies have shown that mesenchymal stem cells (MSCs) can also differentiate (or trans-differentiate) into hepatocytes. Differentiation of human PSCs and MSCs into functional hepatocytelike cells (HLCs) opens new strategies to study genetic diseases, hepatotoxicity, infection of hepatotropic viruses, and analyze hepatic biology. Numerous in vitro and in vivo differentiation protocols have been established to obtain human PSCs/MSCs-derived HLCs and mimic their characteristics. It was recently discovered that microRNAs (miRNAs) play a critical role in controlling the ectopic expression of transcription factors and governing the hepatocyte differentiation of human PSCs and MSCs. In this review, we focused on the role of miRNAs in the differentiation of human PSCs and MSCs into hepatocytes.

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BACKGROUND: Hepatocellular carcinoma (HCC) represents a serious public health problem worldwide and has high morbidity and mortality. Dihydromyricetin (DHM) exhibits anticancer effect on a variety of malignancies, but its anticancer function of DHM in HCC has been unclear. The aim of this study was designed to investigate the anticancer effect of DHM on cell apoptosis, proliferation, migration and invasion of hepatoma carcinoma cells. METHODS: Cultured Hep3B cells were treated with different DHM concentrations, followed by cell apoptosis, proliferation, migration and invasion were examined by CCK-8, colony formation assay, wound healing, Transwell and flow cytometry, respectively. The mRNA and protein expression of BCL-2, Cleaved-caspase 3, Cleaved-caspase 9, BAK, BAX and BAD were validated by western blot. RESULTS: DHM markedly suppressed proliferation, migration, invasion and facilitated apoptosis in Hep3B cells. Mechanistically, DHM significantly downregulated the Bcl-2 expression, and upregulated the mRNA and protein levels of Cleaved-Caspase 3, Cleaved- Caspase 9, Bak, Bax and Bad. Furthermore, in the nude mice tumorigenic model, DHM treatment greatly decreased the weight of the HCC cancers compared to the weights in control and NDP group. CONCLUSIONS: DHM could suppress cell proliferation, migration, invasion, and facilitated apoptosis in Hep3B cells. These findings could provide novel insights to develop potential therapeutic strategy for the clinical treatment of HCC.

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