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 optimize the formulation of ferulic acid ligustrazine (FATM) solid lipid nanoparticles (FATM-SLN),and conduct the quality evaluation. METHODS:Emulsification ultrasonic method was used to prepare FATM-SLN. Using particle size and entrapment efficiency as indexes,amount of glyceryl monostearate,egg yolk lecithin (PC),poloxamer 188 (P188),and sodium stearate as factors,single factor test and orthogonal test were used to optimize the formulation;and verifica-tion test was conducted. The appearance morphology,distribution of particle size,Zeta potential,stability and in vitro release de-gree of prepared FATM-SLN were investigated. RESULTS:The optimal formulation was as follows as FATM of 10 mg,glyceryl monostearate of 300 mg,PC of 200 mg,P188 of 200 mg,sodium stearate of 10 mg,and purified water of 20 mL. The prepared FATM-SLN showed spherical solid particles,appearance morphology was round,distribution of particle size was 40-800 nm,parti-cle size was 106.23 nm,polydispersity index was 0.254,Zeta potential was -34.8 mV,entrapment efficiency was 73.32%,drug loading was 1.20%;the appearance had no obvious changes within 10 d in 4 ℃(RSD<2%). The drug-release in 0.5-1 h was the fastest,the cumulative release degree reached to 60.47%;it tended to be stable after 8 h,the cumulative release degree reached to 93.46%,and drugs were basically released completely. CONCLUSIONS:FATM-SLN formulation is successfully optimized,and the prepared FATM-SLN has small particle size,high entrapment efficiency and good stability.

Objective To study the effects of paeonol on the tyrosinase activity and melanogenesis in co-culture model of human melanocytes and keratinocytes. Methods Melanocytes and the co-culture model of human melanocytes and keratinocytes were cultivated and the proliferation of melanocytes and the co-cultures was measured by MTT colorimetric assay. The tyrosinase activity and melanin level were measured by enzymic method. Results The melanin synthesis and tyrosinase activity were markedly suppressed by paeonol in a dose-dependent manner at the concentrations of 50?mol/L, 100?mol/L, and 200?mol/L in both melanocytes and co-cultures. The significant stronger suppression was observed with 100?mol/L and 200?mol/L of paeonol than that with controls (P