Objective: To establish a hydrogen peroxide (H₂O₂) induced injury model of pulmonary artery endothelial cells (PAECs) and explore the molecular mechanisms of oxidative stress on the structure and function of PAECs in this model. Methods: Human PAECs were treated with H₂O₂ at different concentrations (25, 50, 100, 200, 400, 800, 1 600, 3 200, 6 400 μmol/L) for 4 and 24 h, respectively. The PAECs survival curve was obtained according to the cell viability measured by CCK-8 assay. The cell apoptosis of PAECs was detected by flow cytometry. The reactive oxygen species (ROS) generation and mitochondrial activity were measured using small molecule fluorescent probes. Proteins were extracted and the phosphorylation levels of signal molecules in PAECs were detected by Western blot assays. Results: (1) The effect of H₂O₂ at various concentrations on cell viability of PAECs: cell viability of PAECs decreased in proportion to increasing concentration of H₂O₂ after incubation for 4 h. The half maximal inhibitory concentration (IC₅₀) of PAECs exposed to H₂O₂ for 4 and 24 h were 397.00 and 488.77 μmol/L, respectively. (2) The effect of H₂O₂ on cell apoptosis of PAECs: After H₂O₂ incubation for 4 h, proportions of PAECs at late-apoptosis ((22.58±3.69) %) and necrotic stage( (11.86±4.27)%) were significantly higher than those of control PAECs at late-apoptosis stage( (3.41±1.44)%, P<0.01) and at necrotic stage ((1.94±1.15) % , P<0.05). The survival rate of PAECs post H₂O₂ was dramatically lower than that of control PAECs ((7.98±3.21)% vs. (48.89±8.08)%, P<0.01). However, there is no statistical difference between both groups regarding to the early apoptosis. (3) The effect of H₂O₂ on mitochondrial activity and ROS production of PAECs: the mitochondrial activity and ROS generation of PAECs treated by H₂O₂ were significantly increased compared to those in control PAECs (P<0.01). (4) The effect of H₂O₂ on signaling molecules in PAECs: there was a significant increase in phosphorylation level of Akt in PAECs incubated with H₂O₂ for 30 minutes compared to that in control PAECs (P<0.01), while there was no significant difference in levels of Akt between H₂O₂ treated PAECs and control PAECs. Phosphorylation level of JNK as well as p38 were also significantly upregulated in H₂O₂ treated PAECs (P<0.01). Conclusion H₂O₂ at the concentration of 400 μmol/L could induce human PAECs injuries via the regulation of Akt and MAPK signaling pathways.

Hepatocellular carcinoma （HCC） is a major cause of cancer-related death， and surgical resection remains an important method for radical treatment， but it is urgently needed to solve the problem of high postoperative recurrence rate. Neoadjuvant therapy can reduce the high recurrence rate after surgery， and there are little benefits from neoadjuvant therapy for HCC due to a lack of effective treatment methods in the past. At present， combination therapy based on immune checkpoint inhibitors has a relatively high response rate and has thus changed the treatment landscape for patients with advanced HCC. This urges investigators to reexamine the neoadjuvant treatment strategies for HCC， and it is expected that neoadjuvant therapy can provide new opportunities， reduce the postoperative recurrence rate， and improve the survival rate after treatment. This article discusses the current status and prospects of neoadjuvant therapy for HCC and related hot topics， so as to provide more ideas for exploring neoadjuvant therapy for HCC.