Comparing the prognosis of esophageal adenocarcinoma with bone and liver metastases: A competing risk analysis.

BACKGROUND: About half of the patients with esophageal cancer are presenting with metastasis at initial diagnosis. However, few studies have concerned on the prognostic factors of metastatic esophageal adenocarcinoma (mEAC). This research aimed to investigate the effects of single bone metastasis (BM) and single liver metastasis (LM) on prognosis of mEAC patients. METHODS: Data were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program database. We compared the effects of LM and BM on overall survival (OS), EAC-specific survival (CSS), and EAC-specific death (EASD) by multivariate Cox regression, Kaplan-Meier analysis, and competing risk regression models. RESULTS: A total of 1,278 EAC patients were recruited in this study. Of which 78.95% (1009/1278) were EASD, and 12.68% (162/1278) were non-EAC-specific death (non-EASD). In multivariate Cox regression analysis, surgery, chemotherapy, and AJCC.T2 (vs. T1) were identified as protective factors for OS&CSS, while divorced/separated, single/unmarried (vs. married), grade III-IV (vs. grade I-II) and BM (vs. LM) were identified as risk factors. Competing risk regression analysis further confirmed that surgery and chemotherapy were beneficial to the patients with mEAC, and BM (vs. LM) was a risk factor for mEAC patients when considering the existence of the competitive risk events. CONCLUSION: Our study indicated that mEAC patients with BM face a worse prognosis compared to those with LM. Additionally, surgery and chemotherapy emerge as protective factors for mEAC patients. These findings offer evidence-based insights for clinical management and contribute to the field.

Associations of essential metals with the risk of aortic arch calcification: a cross-sectional study in a mid-aged and older population of Shenzhen, China.

Vascular calcification is a strong predictor of cardiovascular events. Essential metals play critical roles in maintaining human health. However, the association of essential metal levels with risk of aortic arch calcification (AoAC) remains unclear. We measured the plasma concentrations of nine essential metals in a cross-sectional population and evaluated their individual and combined effects on AoAC risk using multiple statistical methods. We also explored the mediating role of fasting glucose. In the logistic regression model, higher quartiles of magnesium and copper were associated with the decreased AoAC risk, while higher quartile of manganese was associated with higher AoAC risk. The least absolute shrinkage and selection operator penalized regression analysis identified magnesium, manganese, calcium, cobalt, and copper as key metals associated with AoAC risk. The weighted quantile sum regression suggested a combined effect of metal mixture. A linear and positive dose-response relationship was found between manganese and AoAC in males. Moreover, blood glucose might mediate a proportion of 9.38% of the association between manganese exposure and AoAC risk. In summary, five essential metal levels were associated with AoAC and showed combined effect. Fasting glucose might play a significant role in mediating manganese exposure-associated AoAC risk.

Inhibition of RIPK1 alleviating vascular smooth muscle cells osteogenic transdifferentiation via Runx2.

Vascular calcification (VC) is recognized as a crucial risk factor for cardiovascular diseases. Our previous report revealed that the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) plays a role in this process. However, the underlying molecular mechanisms remain elusive. Notably, receptor-interacting protein kinase 1 (RIPK1) has been implicated in the development of cardiovascular diseases, yet its role and mechanisms in VC remain unexplored. To address this gap, we established models using chronic kidney disease mice and calcifying VSMCs to investigate the impact of RIPK1 on VC. Subsequently, a RIPK1-specific inhibitor (NEC-1) was applied in both in vitro and in vivo models. Our findings indicate significant activation of RIPK1 in calcified human arterial tissue, as well as in animal and cellular models. RIPK1 activation promotes the osteogenic transdifferentiation of VSMCs. Treatment with the NEC-1 substantially reduced VC. These results demonstrate that RIPK1 is a target for preventing VC.

The mediation effect of HDL-C: Non-HDL-C on the association between inflammatory score and recurrent coronary events.

Background: Inflammation and lipids are both involved in the pathogenesis of coronary heart disease (CHD). However, the mediation effect of lipoproteins on the association between inflammation and recurrent coronary events in CHD patients remains unclear. Methods: This was a retrospective study including CHD patients hospitalized in the Department of Cardiovascular Medicine in Sun Yat-sen Memorial Hospital between January 2011 and December 2012 with the endpoint of recurrent coronary events. The study calculated inflammatory score based on six serum inflammatory markers, including complement C3, complement C4, hyper-sensitive CRP, fibrinogen, D-dimer, and white blood cell count. Logistic regression analysis, subgroup analysis and mediation analysis were performed to assess the associations between inflammatory score and recurrent coronary events in different subpopulations and the identification of mediators. Inflammatory cytokine expression, cholesterol efflux capacity, and hepatic cholesterol influx were performed in additional CHD patients and healthy controls. Results: There were 191 CHD patients included in the analysis with a median inflammatory score of -0.78 (-2.17, 1.35) and 63 cases of recurrent coronary events. Subgroup logistic regression analysis demonstrated that inflammatory score was positively associated with recurrent coronary events only in the diabetic subgroup [OR: 1.241 (1.004, 1.534), P < 0.046]. HDL-cholesterol (HDL-C): non-HDL-C performed 46.74 % of negative mediation effect on this association. CHD patients had lower cholesterol efflux capacity than healthy controls, which was mediated by HDL: non-HDL ratio of 0.4. No difference was found in hepatic cholesterol influx between the two groups. Conclusion: Inflammatory score was associated with recurrent coronary events mediated by HDL-C: non-HDL-C ratio in diabetic CHD patients, indicating that lipoproteins might aggravate the inflammatory effect on atherosclerosis under hyperglycemia. Our findings suggested that anti-inflammatory and lipid-lowering therapies might be beneficial for this population.