The interaction between cancer cells and immune cells plays critical roles in gastric cancer (GC) progression and immune evasion. Forced legumain (LGMN) is one of the characteristics correlated with poor prognosis in gastric cancer patients. However, the role of gastric-cancer-secreted LGMN (sLGMN) in modulating the tumor immune microenvironment and the biological effect on the immune evasion of gastric cancer remains unclear. In this study, we found that forced expression of sLGMN in gastric cancer serum correlates with increased M2 macrophage infiltration in GC tissues and predicted resistance to anti-PD-1 immunotherapy. Mechanistically, gastric cancer cells secrete LGMN via binding to cell surface Integrin αvβ3, then activate Integrin αvβ3/PI3K (Phosphatidylinositol-4,5-bisphosphate3-kinase)/AKT (serine/threonine kinase)/mTORC2 (mammalian target of rapamycin complex 2) signaling, promote metabolic reprogramming, and polarize macrophages from the M1 to the M2 phenotype. Either blocking LGMN, Integrin αv, or knocking out Integrin αv expression and abolishing the LGMN/Integrin αvβ3 interaction significantly inhibits metabolic reprogramming and polarizes macrophages from the M1 to the M2 phenotype. This study reveals a critical molecular crosstalk between gastric cancer cells and macrophages through the sLGMN/Integrinαvβ3/PI3K/AKT/mTORC2 axis in promoting gastric cancer immune evasion and resistance to anti-PD-1 immunotherapy, indicating that the sLGMN/Integrinαvβ3/PI3K/AKT/mTORC2 axis may act as a promising therapeutic target.

Idiopathic pulmonary arterial hypertension (IPAH) is a rare vascular disease with a poor prognosis, and the mechanism of its development remains unclear. Further molecular pathology studies may contribute to a comprehensive understanding of IPAH and provide new insights into diagnostic markers and potential therapeutic targets. Iron deficiency has been reported in 43‐63% of patients with IPAH and is associated with reduced exercise capacity and higher mortality, suggesting that dysregulated iron metabolism may play an unrecognized role in influencing the development of IPAH. In this study, we explored the regulatory mechanisms of iron metabolism in IPAH by bioinformatic analysis. The molecular function of iron metabolism‐related genes (IMRGs) is mainly enriched in active transmembrane transporter activity, and they mainly affect the biological process of response to oxidative stress. Ferroptosis and fluid shear stress and atherosclerosis pathways may be the critical pathways regulating iron metabolism in IPAH. We further identified 7 key genes (BCL2, GCLM, MSMO1, SLC7A11, SRXN1, TSPAN5, and TXNRD1) and 5 of the key genes (BCL2, MSMO1, SLC7A11, TSPAN5, and TXNRD1) as target genes may be regulated by 6 dysregulated miRNAs (miR‐483‐5p, miR‐27a‐3p, miR‐27b‐3p, miR‐26b‐5p, miR‐199a‐5p, and miR‐23b‐3p) in IPAH. In addition, we predicted potential IPAH drugs—celastrol and cinnamaldehyde—that target iron metabolism based on our results. These results provide insights for further definition of the role of dysregulated iron metabolism in IPAH and contribute to a deeper understanding of the molecular mechanisms and potential therapeutic targets of IPAH.

There is an increasing demand for minimally invasive aortic valve replacement. This study aimed to investigate the safety and feasibility of minimally invasive aortic valve replacement through a right parasternal second intercostal transverse incision. This was a retrospective study, and we collected information from 111 patients who underwent isolated aortic valve replacement surgery performed by the same surgeon from January 2018 to December 2019. According to the operative approach, the patients were divided into a sternotomy aortic valve replacement (SAVR) group (n = 62) and a minimally invasive aortic valve replacement (Mini-AVR) group (n = 49). We compared the intraoperative and postoperative data between the two groups. There was no difference in preoperative data between the Mini-AVR and SAVR. The postoperative ventilator-assisted time, CSICU time and postoperative hospital stay of the Mini-AVR were shorter than those of the SAVR [(15.45 ± 5.75) VS (18.51 ± 6.71) h; (1.77 ± 0.31) VS (2.04 ± 0.63) d; (8.69 ± 2.75) VS (10.77 ± 2.94) d], and the difference was statistically significant (P < 0.05). Mini-AVR had lower postoperative drainage and blood transfusion rates in the first 24 h than SAVR [(109.86 ± 125.98) VS (508.84 ± 311.70) ml; 22.4% VS 46.8%], and the differences were statistically significant (P < 0.05). The incidence of postoperative AF in the Mini-AVR group was also lower than that in the SAVR group (10.2% VS 30.6%), and the differences were statistically significant (P < 0.05). Mini-AVR has the advantages of less ventilator time, a reduced need for blood transfusion, less AF and a faster recovery. Mini-AVR is a safe and feasible surgical technique that is worthy of clinical application.