Objective:To investigate the effect of cumulative serum uric acid (cumSUA) on early-onset ischemic stroke in young adults.Methods:A prospective cohort study was conducted. A total of 15 607 Kailuan workers who participated in at least two physical check-ups in 2006 and 2008 and at the time of the last physical check-up before 2014 were selected as subjects. Cumulative uric acid exposure during the follow-up period was calculated. The subjects were divided into three groups according to the quantile of cumSUA: the first quantile group was cumSUA<1 563 μmol/L·year, the second quantile group was: 1 563 μmol/L·year≤cumSUA<1 996 μmol/L·year, the third group was cumSUA≥1 996 μmol/L·year. The time of the last physical check-up was regarded as the starting point of follow-up, and early-onset ischemic stroke was regarded as the end event. Kaplan-Meier was used to calculate the incidence of early-onset ischemic stroke in different groups, and Log-rank method was used to calculate the differences in the incidence of early-onset ischemic stroke among different groups. Multivariate Cox regression model was used to analyze the risk of early-onset ischemic stroke in different groups. A four-node (5th, 25th, 75th, 95th percentile) restricted cubic spline plot was used to assess the dose-response relationship between cumSUA and early-onset ischemic stroke.Results:A total of 15 607 subjects were followed up for (7.3±1.1) years. 100 cases with early-onset ischemic stroke were observed with an average age of (46±4) years old. The number of events in the first, second, and third quartile groups was 18, 35, and 47, respectively, and the cumulative incidence rates in the first, second, and third quartile groups were 0.40%, 0.77%, and 1.07%, respectively. The difference in cumulative incidence of endpoint events between the groups was statistically significant by Log-rank test ( χ2=14.96, P=0.003). The results of Cox regression analysis showed that after correcting for confounders, the HR(95% CI) for early-onset ischemic stroke in the second and third quartile groups was [1.67(0.92,3.00), P=0.090; 2.05(1.48,3.69), P=0.020]. Restricted cubic spline results showed a nonlinear correlation between cumSUA and early-onset ischemic stroke after adjysted for confounders. Conclusion:Cumulative serum uric acid is positively correlated with the risk of early-onset ischemic stroke in young adults.

Tumors still perform glycolysis in the aerobic environment to accelerate the uptake of glucose and produce a large amount of lactic acid in tumor microenvironment, provide biomolecular precursors of nucleotides, lipids, and proteins for tumor cell proliferation, and inhibit the function of immune cells and promote the metastasis of tumor cells in acidic environment. Gluconeogenesis, as the reverse reaction of glycolysis, is inhibited in hepatocellular carcinoma, especially the downregulated expression of the four key rate-limiting enzymes pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1, 6-diphosphate 1, and glucose-6-phosphatase 4, which promotes the growth and proliferation of hepatocellular carcinoma by promoting aerobic glycolysis and its branched pathways, and meanwhile, it is also associated with the overall survival time and prognosis of patients with hepatocellular carcinoma and is considered an inhibitor for hepatocellular carcinoma. Therefore, this review summarizes the changes and mechanism of action of the key enzymes of gluconeogenesis in the development and progression of hepatocellular carcinoma and analyzes the shortcomings and future directions of related research in hepatocellular carcinoma, so as to provide new ideas for the treatment of hepatocellular carcinoma.

ObjectiveTo investigate the influence of triglyceride （TG）/high-density lipoprotein cholesterol （HDL-C） ratio on the onset of primary liver cancer. MethodsA prospective cohort study was conducted. Physical examination data were collected from 99 750 cases of on-the-job and retired employees of Kailuan Group who participated health examination from July 2006 to December 2007， and they were followed up till December 31， 2021 to observe the onset of primary liver cancer. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between multiple groups； the chi-square test was used for comparison of categorical data between groups. According to the tertiles of TG/HDL-C ratio， the subjects were divided into Q1， Q2， and Q3 groups， and the incidence density of primary liver cancer was calculated for each group. The Kaplan-Meier method was used to calculate the cumulative incidence rate of primary liver cancer in each group， and the log-rank test was used to compare the difference in cumulative incidence rate between groups. The Cox proportional hazards model was used to analyze the influence of TG/HDL-C ratio on the onset of primary liver cancer. ResultsThere were significant differences between the three groups in age， proportion of male subjects， waist circumference， body mass index， fasting blood glucose， systolic pressure， diastolic pressure， triglyceride， total cholesterol， HDL-C， low-density lipoprotein cholesterol， alanine aminotransferase， high-sensitivity C-reactive protein， chronic liver diseases， hypertension， diabetes， the family history of malignant tumor， drinking， smoking， physical exercise， and educational level （P<0.05）. During the mean follow-up time of 14.06±2.71 years， there were 484 cases of new-onset liver cancer， among whom there were 446 male subjects and 38 female subjects. The incidence density of primary liver cancer was 0.39/1 000 person-years in the Q1 group， 0.35/1 000 person-years in the Q2 group， and 0.30/1 000 person-years in the Q3 group， and the cumulative incidence rates of primary liver cancer in the three groups were 6.03‰， 5.28‰， and 4.49‰， respectively， with a significant difference between the three groups based on the long-rank test （χ²=6.06， P=0.048）. After adjustment for the confounding factors considered， the Cox proportional hazards model showed that compared with the Q3 group， the Q1 group had a hazard ratio of 2.04 （95% confidence interval ［CI］： 1.61‍ ‍—‍ ‍2.58， P_{for trend}<0.05）， and the Q2 group had a hazard ratio of 1.53 （95%CI： 1.21‍ ‍—‍ ‍1.92， P_{for trend}<0.05）. ConclusionThe reduction in TG/HDL-C ratio is associated with an increase in the rask of primary liver cancer， especially in people with chronic liver diseases.