Identification of Fangjihuangqi Decoction as a late-stage autophagy inhibitor with an adjuvant anti-tumor effect against non-small cell lung cancer.

BACKGROUND: Clinically, although chemotherapy is one of the most commonly used methods of treating tumors, chemotherapeutic drugs can induce autophagic flux and increase tumor cell resistance, leading to drug tolerance. Therefore, theoretically, inhibiting autophagy may improve the efficacy of chemotherapy. The discovery of autophagy regulators and their potential application as adjuvant anti-cancer drugs is of substantial importance. In this study, we clarified that Fangjihuangqi Decoction (FJHQ, traditional Chinese medicine) is an autophagy inhibitor, which can synergistically enhance the effect of cisplatin and paclitaxel on non-small cell lung cancer (NSCLC) cells. METHODS: We observed the changes of autophagy level in NSCLC cells under the effect of FJHQ, and verified the level of the autophagy marker protein and cathepsin. Apoptosis was detected after the combination of FJHQ with cisplatin or paclitaxel, and NAC (ROS scavenger) was further used to verify the activation of ROS-MAPK pathway by FJHQ. RESULTS: We observed that FJHQ induced autophagosomes in NSCLC cells and increased the levels of P62 and LC3-II protein expression in a concentration- and time-gradient-dependent manner, indicating that autophagic flux was inhibited. Co-localization experiments further showed that while FJHQ did not inhibit autophagosome and lysosome fusion, it affected the maturation of cathepsin and thus inhibited the autophagic pathway. Finally, we found that the combination of FJHQ with cisplatin or paclitaxel increased the apoptosis rate of NSCLC cells, due to increased ROS accumulation and further activation of the ROS-MAPK pathway. This synergistic effect could be reversed by NAC. CONCLUSION: Collectively, these results demonstrate that FJHQ is a novel late-stage autophagy inhibitor that can amplify the anti-tumor effect of cisplatin and paclitaxel against NSCLC cells.

Ideal cardiovascular health and mortality: pooled results of three prospective cohorts in Chinese adults.

BACKGROUND: Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps. METHODS: A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis. RESULTS: During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed. CONCLUSIONS: ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.

Blood Pressure Classification of 2017 Associated With Cardiovascular Disease and Mortality in Young Chinese Adults.

The American College of Cardiology/American Heart Association introduced new guidelines for blood pressure (BP) classification in 2017. We explored associations between the newly defined categories and eventual cardiovascular disease (CVD) events, stroke, and all-cause mortality in young Chinese adults. In the community-based Kailuan Study, 16 006 participants aged 18 to 40 years and examined at baseline in 2006/2007 underwent 2-yearly follow-up examinations up to 2016 to 2017. Taking the highest BP reading recorded by manual sphygmomanometry at baseline in 2006 to 2007, we categorized the BP according to the new guidelines. Outcome parameters were CVD events, stroke, and all-cause mortality. During follow-up (mean: 10.9±0.63 years), we observed 458 events (CVD, 167; stroke, 119; and all-cause death, 172). After multivariable adjustment, hazard ratios for CVD events were for elevated BP 0.80 (95% CI, 0.28-2.30), stage 1 hypertension 1.82 (95% CI, 1.12-2.94), and stage 2 hypertension 3.54 (95% CI, 2.18-5.77) versus normal BP. Similar results were obtained for stroke and all-cause death. In Cox regression analysis with BP category entered as time-dependent covariate, stage 1 hypertension was not associated with increased risk (P>0.10). In the subgroup of individuals taking antihypertensive medication during follow-up, none of the BP categories was significantly associated with the incidence of CVD events. During a mean follow-up of 10.9 years, the newly defined category of stage 1 hypertension in young untreated Chinese adults aged <40 years at baseline was associated with an increased risk for CVD, stroke, and all-cause mortality. This increased risk occurred, however, after progression to stage 2 hypertension. The data may help validating the new BP classification system for young adult Chinese.