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 detect the single nucleotide polymorphism (SNP) at locus 1 165 of β1-adrenoceptor (β1-AR) and to investigate the association between the SNP and the infection by enterovirus A71(EV-A71). Methods: Polymerase chain reaction (PCR) amplification technique was used to detect the SNP at locus 1 165 of β1-AR between hand, foot and mouth disease (HFMD) and healthy controls by sanger sequencing method . Results: There was a G1165C SNP and three kinds of genotypes (GG, GC, CC) in β1-AR gene in the 77 cases of EV-A71 HFMD patients and 66 cases of healthy controls. For HFMD patients, frequencies of GG, GC and CC genotypes of the G1165C locus were 10%, 47% and 43%, respectively, and alleles frequency of G and C were 34% and 66%, respectively. But in healthy children, GG, GC, CC genotype frequencies were 7%, 41% and 52%, respectively, and G and C allele frequencies were 28% and 72% respectively. Chi-square analysis showed that there were no significant differences in distribution of genotypes (χ²=1.154, df=2, P=0.562) and alleles frequency (χ²=1.091, df=2, P=0.296) between the EV-A71-infected group and the healthy control group. Between mild and severe EV-A71-infected group, there were no significant differences in distribution of genotypes (χ²=3.945, df=2, P=0.139) and alleles frequency (χ²=3.763, df=2, P=0.052). Conclusions The 1 165 SNP in the coding region of β1-AR was not associated with EV-A71 infection and its severity.

Objective To investigate the predictive value of symmetrical ambulatory arterial stiffness index (S-AASI) in detecting early renal impairment of patients with essential hypertension.Methods Totally 245 consecutive out-patients were confirmed with essential hypertension,and were divided into group A (56 cases),group B (64 cases),group C (72 cases),and group D (53 cases) according to the quartile of S-AASI.The combination testing of serum cystatin C,serum β2-microglobulin as well as urine microalbumin to creatinine ratio were implemented as laboratory diagnosis index of renal impairment in early stage and 109 essential hypertension patients were diagnosed with early renal impairment.The parameters were compared among 4 groups.Pearson correlation analysis and partial correlation analysis were performed to confirm the relationship between the markers of early renal impairment and S-AASI.The predictive value of S-AASI to detect early renal injury was evaluated by analyzing Receiver Operating Characteristic (ROC) curve.Results With the rising of S-AASI,age as well as 24 hours mean systolic blood pressure (24 h SBP),serum cystatin C,serum β2-microglobulin,urine microalbumin to creatinine ratio and the incidence rate of early renal injury went notably higher while estimated glomerular filtration rate (eGFR) decreased significantly.After controlling for age,correlation test showed S-AASI was positively correlated with24hSBP,serum cystatin C,serumβ2-microglobulin,urine microalbumin to creatinine ratio(r =0.392,0.627,0.514 and 0.643 respectively,P ＜ 0.05) and negatively correlated with eGFR(r =-0.312,P ＜ 0.05).The 24 hours mean diastolic blood pressure (24 h DBP) was uncorrelated with S-AASI.Area under ROC curve of S-AASI for diagnosis of hypertensive renal impairment was 0.885.The critical value of S-AA-SI was 0.17,the sensitivity,specificity,positive predictive value,and negative predictive value were 92.7％,65.2％,68.5％,and 91.7％,respectively.Conclusions When S-AASI was detected above 0.17,patients with hypertension had a higher risk of renal impairment.Higher S-AASI was correlated with worse early renal impairment laboratory indexes.The predictive accuracy of S-AASI for early hypertensive renal impairment was medium.