Objective: To examine the relation between mobile phone addiction and high school students’ depression, and its inner mechanism—the sequential mediating roles of the cyberbullying victimization and the cyberbullying perpetration in this relationship.Methods: 1297 high school students were recruited to complete the Smartphone Addiction Scale, European Cyberbullying Intervention Project Questionnaire and the Center for Epidemiological Studies Depression Scale.Results: (1) Mobile phone addiction was positively correlated with and high school students’ depression; (2) cyberbullying victimization and the cyberbullying perpetration significantly mediated the relation between mobile phone addiction and high school students’ depression, which contained tow mediating paths—the independent mediating effects of cyberbullying victimization and the sequential mediating effect of cyberbullying victimization and the cyberbullying perpetration; (3) there are gender differences in the sequential mediation model, and boys who are victims of cyberbullying are more likely to develop into cyberbullying perpetrators than girls.Conclusion: The results of this study indicate that depression among high school students with mobile phone addiction can be eliminated through the development of cyberbullying victimization and the cyberbullying perpetration.

Acquired drug resistance represents a major obstacle to using sunitinib for the treatment of solid tumors. Here, we examined the cellular and molecular alterations in tumors that are associated with acquired brain tumor resistance to sunitinib by using an in vivo model. U87MG tumors obtained from nude mice that received sunitinib (40 mg/kg/day) for 30 days were classified into sunitinib-sensitive and -resistant groups based on tumor volume and underwent targeted gene microarray and protein array analyses. The expression of several angiogenesis-associated genes was significantly modulated in sunitinib-treated tumors compared with those in control tumors (p < 0.05), whereas no significant differences were observed between sunitinib-sensitive and -resistant tumors (p > 0.05). Tumor vasculature based on microvessel density, neurogenin 2 chondroitin sulfate proteoglycan density, and α-smooth muscle actin density was also similar in sunitinib-treatment groups (p > 0.05). The moderate increase in unbound sunitinib tumor-to-plasma area-under-the-curve ratio in sunitinib-resistant mice was accompanied by up-regulated ATP-binding cassette G2 expression in tumor. The most profound difference between the sunitinib-sensitive and -resistant groups was found in the expression of several phosphorylated proteins involved in intracellular signaling. In particular, phospholipase C-γ1 phosphorylation in sunitinib-resistant tumors was up-regulated by 2.6-fold compared with that in sunitinib-sensitive tumors (p < 0.05). In conclusion, acquired sunitinib resistance in U87MG tumors is not associated with revascularization in tumors, but rather with the activation of alternate prosurvival pathways involved in an escape mechanism facilitating tumor growth and possibly insufficient drug uptake in tumor cells caused by an up-regulated membrane efflux transporter.

Background/Objectives: Ropivacaine is primarily metabolized by the liver. High doses of ropivacaine, combined with altered pharmacokinetics due to hepatectomy, raise concerns about potential drug toxicity. We investigated the impact of LMH (laparoscopic major hepatectomy) on the pharmacokinetics of high-dose ropivacaine. Methods: Ten patients undergoing LMH received a BD-TAP (bilateral dual transversus abdominis plane) block with a high dose of ropivacaine (3 mg·kg⁻¹ in 60 mL). Plasma concentrations of total and free ropivacaine and AAG (alpha-1 acid glycoprotein) levels were measured. Liver volumes were calculated using three-dimensional liver reconstruction technology. Results: The peak total ropivacaine concentration occurred 45 min after the block, reaching 2031.5 (876.0) ng·mL⁻¹, with a tendency to exceed the toxicity threshold in patients with a CFLV (cut functional liver volume) exceeding 199.24 mL or a CFLV/TFLV (total functional liver volume) ratio surpassing 18.61%. The peak free ropivacaine concentration, 111.5 (31.3) ng·mL⁻¹, was observed 90 min after the block, potentially exceeding the toxicity threshold when CFLV exceeded 452.33 mL or the CFLV/TFLV ratio was greater than 42.16%. Plasma AAG levels increased approximately 1.5 times within 24 h, from 1519.7 (422.6) μg·mL⁻¹ preoperatively to 2253.6 (460.4) μg·mL⁻¹ postoperatively, effectively reducing the toxicity risk associated with free ropivacaine. Conclusions: Preoperative administration of high-dose ropivacaine can be safely utilized in patients undergoing major hepatectomy. The increased plasma AAG concentration due to surgical stress reduces free ropivacaine levels, enhancing patient tolerance to the drug. The CFLV and CFLV/TFLV ratio may be supplementary indicators for predicting ropivacaine toxicity.