Background: The prognostic significance of tumor burden score (TBS) on patients who underwent curative-intent resection of intrahepatic cholangiocarcinoma (ICC) has not been evaluated. The present study aimed to investigate the impact of TBS and its synergistic effect with CA19-9 (combination of TBS and CA19-9, CTC grade) on long-term outcomes.Methods: Patients who underwent radical resection of ICC between 2009 and 2017 were retrospectively identified from a multi-center database. The overall survival (OS) and recurrence-free survival (RFS) were examined in relation to TBS, serum preoperative CA19-9, and CTC grade.Results: A total of 650 patients were included in our study (509 in the derivation cohort and 141 in the validation cohort). Kaplan–Meier curves showed that both TBS and CA19-9 levels were strong predictors of survival outcomes. Patients with elevated TBS grade or elevated CA19-9 were associated with worse OS and RFS (both p < 0.001). As expected, CTC grade also performed well in predicting long-term outcomes. Patients with low TBS/low CA19-9 (CTC grade 1) were associated with the best OS as well as RFS, while high TBS/high CA19-9 (CTC grade 3) correlated to the worst outcomes. In the validation cohort, TBS grade, preoperative CA19-9, and CTC grade also stratified prognosis among patients (p < 0.001 for each).Conclusions: Both tumor morphology (tumor burden) and tumor-specific biomarker (serum CA19-9) were important when evaluating prognosis of patients with resectable ICC. Serum CA19-9 and TBS showed a synergistic effect on prognostic evaluation. CTC grade was a promising tool in stratifying prognosis of ICC patients after curative resection.

Background: Hepatic ischemia/reperfusion (I/R) injury is one of the major pathological processes associated with various liver surgeries. However, there is still a lack of strategies to protect against hepatic I/R injury because of the unknown underlying mechanism. The present study aimed to identify a potential strategy and provide a fundamental experimental basis for treating hepatic I/R injury. Method: A classic 70% ischemia/reperfusion injury was established. Immunoprecipitation was used to identify direct interactions between proteins. The expression of proteins from different subcellular localizations was detected by Western blotting. Cell translocation was directly observed by immunofluorescence. HE, TUNEL and ELISA were performed for function tests. Result: We report that tripartite motif containing 37 (TRIM37) aggravates hepatic I/R injury through the reinforcement of IKK-induced inflammation following dual patterns. Mechanistically, TRIM37 directly interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6), inducing K63 ubiquitination and eventually leading to the phosphorylation of IKKβ. TRIM37 enhances the translocation of IKKγ, a regulatory subunit of the IKK complex, from the nucleus to the cytoplasm, thereby stabilizing the cytoplasmic IKK complex and prolonging the duration of inflammation. Inhibition of IKK rescued the function of TRIM37 in vivo and in vitro. Conclusion: Collectively, the present study discloses some potential function of TRIM37 in hepatic I/R injury. Targeting TRIM37 might be potential for treatment against hepatic I/R injury.Targeting TRIM37 might be a potential treatment strategy against hepatic I/R injury. Graphical