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Zheyu Yang,Yu Heng,Jianwei Lin,Chenghao Lu,Dingye Yu,Lei Tao,Wei Cai 대한암학회 2020 Cancer Research and Treatment Vol.52 No.4
Purpose Central lymph node metastasis (CNM) are highly prevalent but hard to detect preoperatively in papillary thyroid carcinoma (PTC) patients, while the significance of prophylactic compartment central lymph node dissection (CLND) remains controversial as a treatment option. We aim to establish a nomogram assessing risks of CNM in PTC patients, and explore whether prophylactic CLND should be recommended. Materials and Methods One thousand four hundred thirty-eight patients from two clinical centers that underwent thyroidectomy with CLND for PTC within the period 2016-2019 were retrospectively analyzed. Univariate and multivariate analysis were performed to examine risk factors associated with CNM. A nomogram for predicting CNM was established, thereafter internally and externally validated. Results Seven variables were found to be significantly associated with CNM and were used to construct the model. These were as follows: thyroid capsular invasion, multifocality, creatinine > 70 μmol/L, age < 40, tumor size > 1 cm, body mass index < 22, and carcinoembryonic antigen > 1 ng/mL. The nomogram had good discrimination with a concordance index of 0.854 (95% confidence interval [CI], 0.843 to 0.867), supported by an external validation point estimate of 0.825 (95% CI, 0.793 to 0.857). A decision curve analysis was made to evaluate nomogram and ultrasonography for predicting CNM. Conclusion A validated nomogram utilizing readily available preoperative variables was developed to predict the probability of central lymph node metastases in patients presenting with PTC. This nomogram may help surgeons make appropriate surgical decisions in the management of PTC, especially in terms of whether prophylactic CLND is warranted.
Chen Liang,Liu Yuting,Wang Zheyu,Zhang Leiyang,Xu Yi,Li Yinan,Zhang Lan,Wang Guiming,Yang Shuofei,Xue Guanhua 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Neutrophil extracellular traps (NETs) play an important role in abdominal aortic aneurysm (AAA) formation; however, the underlying molecular mechanisms remain unclear. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) may exert therapeutic effects on AAA through their immunomodulatory and regenerative abilities. This study aimed to examine the role and mechanism of MSC-EVs in regulating the development of NET-mediated AAA. Excessive release of NETs was observed in patients with AAA, and the levels of NET components were associated with the clinical outcomes of the patients. Datasets from the Gene Expression Omnibus database were analyzed and revealed that the PI3K/AKT pathway and ferroptosis were strongly associated with NETosis during AAA formation. Further experiments verified that NETs promoted AAA formation by inducing ferroptosis in smooth muscle cells (SMCs) by inhibiting the PI3K/AKT pathway. The PI3K agonist 740 Y-P, the ferroptosis inhibitor ferrostatin-1, and Padi4 deficiency significantly prevented AAA formation. MSC-EVs attenuated AAA formation by reducing NET release in an angiotensin II-induced AAA mouse model. In vitro experiments revealed that MSC-EVs reduced the release of NETs by shifting NETosis to apoptosis. Our study indicates an important role for NET-induced SMC ferroptosis in AAA formation and provides several potential targets for AAA treatment