In the context of the development of transplant oncology, it is of great clinical significance to find a drug with both antitumor and immunosuppressive effects for liver transplantation patients with hepatocellular carcinoma (HCC). The antitumor effect of ginkgolic acid (GA) has been confirmed, and some studies suggest that GA may also have an immunosuppressive effect. The immunosuppressive effect of GA was evaluated by histopathology, T-cell subpopulation, and cytokine detection in rat liver transplantation and mouse cardiac transplantation models, and transcriptomic and metabolomic analysis was used to explore the underlying mechanism of the GA immunosuppressive effect. Metabolites, activation, and ferroptosis markers of CD8⁺ T cells were detected in vivo and in vitro. Based on rat liver transplantation and mouse cardiac transplantation models, the immunosuppressive effect of GA was first confirmed by histopathology, T-cell subpopulation, and cytokine detection. In the mouse cardiac transplantation model, transcriptomics combined with metabolomics demonstrated for the first time that GA inhibited lactate dehydrogenase A (LDHA) expression and pyruvate metabolism in CD8⁺ T cells. It was confirmed in vivo and in vitro that GA inhibited pyruvate metabolism of CD8⁺ T cells through LDHA, inhibiting their activation and inducing ferroptosis. Overexpression of LDHA partially reversed the effect of GA on the metabolism, activation, and ferroptosis of CD8⁺ T cells in vitro. GA mediates metabolic reprogramming through LDHA to inhibit the activation and induce ferroptosis of CD8⁺ T cells to exert an immunosuppressive effect, which lays an experimental foundation for the future clinical application of its immunosuppressive effect.

Objective:To compare ultrasound (US) guided versus computed tomography (CT) guided radiofrequency ablation (RFA) in treatment of early hepatocellular carcinoma (HCC).Methods:The data of 133 patients with early HCC treated by RFA in the Department of Hepatobiliary Surgery of Shandong Provincial Hospital from February 1, 2015, to January 31, 2017, was analyzed retrospectively. These patients were divided into two groups: the US-guided group and the CT-guided group. The clinical data was collected and the factors affecting prognosis were analyzed.Results:Compared with the CT-guided group, the operation time of the US-guided group was significantly shorter [(29.0±12.0)min vs. (55.0±19.0)min, P<0.05], but the number of ablation sessions per tumor was significantly less [(1.1±0.3) vs. (2.0±0.6), P<0.05]. There was no significant difference in the complete ablation rates, postoperative complication rates and postoperative length of hospital stay between the two groups ( P>0.05). The CT-guided group was superior to the US-guided group in the local tumor recurrence and progression-free survival rates ( P<0.05). On multivariate analysis, CT-guided RFA was an independent protective factor for local tumor recurrence ( HR=0.266, 95% CI: 0.073-0.967, P<0.05) and progression-free survival ( HR=0.415. 95% CI: 0.213-0.806, P<0.05), while AFP >20 ng/ml ( HR=4.821, 95% CI: 1.714-13.560, P<0.05) was an independent risk factor for progression-free survival. Conclusion:CT-guided percutaneous RFA was superior to US-guided RFA in local treatment of early HCC, probably related to more needle placements and longer ablation time under CT guidance.