Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

Objective:To analyze the application and funding status of various projects of nuclear medicine and molecular imaging supported by the National Natural Science Foundation of China (NSFC) from 2013 to 2022, and explore the challenges faced by basic research and clinical transformation in this field.Methods:From 2013 to 2022, application and funding information of nuclear medicine and molecular imaging projects (secondary code H2704, H2706) from five departments of Medical Science Department of NSFC were retrospectively collected. The number of applications, number of funding, funding direction, funding intensity, distribution of supporting units and research hotspots of various projects in this field were analyzed.Results:From 2013 to 2022, the total number of applications of various projects in the field of nuclear medicine and molecular imaging reached 5 387, and the total number of grants reached 899. The number of applications and grants showed a steady growth trend. The overall funding intensity increased from 48.935 0 million yuan in 2013 to 59.495 4 million yuan in 2022, with the increase of 21.58%. Among all supporting units, Shanghai Jiao Tong University topped the list for both the number of applications (440) and the number of grants (82), Xiamen University ranked the first in terms of overall funding rate (25.42%, 30/118), and Peking University ranked the first in terms of total funding intensity (41.897 1 million yuan). Research hotspots focused on the construction of tumor targeted molecular probes and precise imaging of tumor internal molecular components.Conclusion:In the past decade, the number of related projects and total funding of nuclear medicine and molecular imaging supported by NSFC have steadily increased, and the types of funded projects are diverse and interdisciplinary, promoting the innovative development of nuclear medicine and molecular imaging disciplines in China.

Objective To investigate the inhibitory effects of oridonin combined with gemcitabine on pancreatic cancer SW1990 cells in vitro, and the potential mechanisms thereof. Methods The pancreatic cancer SW1990 cells were treated with vehicle alone and various concentrations (10,20,40,80 and160μmol/L) of oridonin, followed by 24, 48 and 72 h cell culture. Effects of oridonin on cell proliferation were determined by using a CCK-8 kit. SW1990 cells were treated with oridonin (40μmol/L) and gemcitabine (20μmol/L) alone or together for 48 h, and the untreated cells were used as the con-trol. The cell survival rate was detected by CCK-8 assay. Apoptosis induction was assessed by using Annexin V-FITC kit. Semi-quantitative RT-PCR was used to examine the changes of NF-κB mRNA and XIAP mRNA expressions. Results Oridonin inhibited the growth of pancreatic cancer SW1990 cells in a dose-and time-dependent manner. Compared with the other groups, the cell survival rate was significantly lower in the combination group (P<0.05). Oridonin combined with gemcitabine induced a higher percentage of apoptosis in pancreatic cancer cells than that of oridonin or gemcitabine alone (P<0.05). Moreover, the expressions of NF-κB and XIAP mRNA in pancreatic carcinoma cells were obviously down-regu-lated in combination group (P<0.05). Conclusion Oridonin can enhance the antitumor effect of gemcitabine on pancreatic cancer in vitro, which may be related to through the down-regulation of NF-κB and its downstream of XIAP, and then induc-ing cell apoptosis in pancreatic cancer.