Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

Excessive Fructose Intake Impairs Baroreflex Sensitivity and Led to Elevated Blood Pressure in Rats.

Hypertension development with an increased intake of added sugar, especially excessive fructose intake, was shown in the National Health and Nutrition Examination Survey (NHANES) data. However, the mechanism underlying blood pressure (BP) elevation with increased fructose intake is still unclear. First, the present study showed that in rats fed 10% fructose for one week, BP and fructose/glucose levels increased in the central and peripheral nervous system. Furthermore, increased fructose intake resulted in an upregulation of fructose concentration in the cerebrospinal fluid. Second, consumption of excess fructose increased serum triglycerides. However, the inhibition of triglyceride production did not mitigate sympathetic nerve hyperactivity, but contributed to an insignificant decrease in BP. Finally, increased fructose intake reduced nitric oxide (NO) levels in the nucleus tractus solitarii (NTS) and reduced baroreflex sensitivity within a week. Collectively, the data suggested that fructose intake reduced NO levels in the NTS and caused baroreflex dysfunction, which further stimulated sympathetic nerve activity and induced the development of high BP.