BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.

Objective To evaluate the clinical efficacy and safety of 1aparoscopy-assisted distal gastrectomy (LADG) for patients with advanced gastric cancer. Methods Clinical data of 198 cases with advanced gastric cancer were retrospectively analyzed. Based on the surgical approach, patients were divided into laparotomy group (n = 101) and laparoscopic group (n = 97), and the intraoperative situation, postoperative complications and quality of life were compared. Results There were no statistical differences in operation time [(226.30 ± 36.40) vs (220.50 ± 29.90) min, t = 1.23, P = 0.221)], number of lymph node cleaning [(22.01 ± 4.99) vs (20.69 ± 4.53), t = 1.95, P = 0.053] between the two groups; the blood loss of laparoscopy group was less than the laparotomy group [(114.50 ± 20.30) vs (168.30 ± 40.04) ml, t = 11.77, P = 0.000]; gastrointestinal function recovery time of laparoscopy group was less than laparotomy group [(72.30 ± 7.91) vs (84.05 ± 9.04) h, t = 9.72, P = 0.000); hospital stay of laparoscopy group was less than the laparotomy group [(8.89 ± 1.57) vs (10.36 ± 2.65) d, t = 4.72, P = 0.000]; there were no statistical differences in the tumor proximal cut end [(5.07 ± 2.04) vs (4.85 ± 1.98) cm, t = 0.77, P = 0.442) and margin of distal [(4.33 ± 1.90) vs (3.90 ± 2.02) cm, t = 1.54, P = 0.125] between the two groups; the postoperative complication rate of laparoscopy group and laparotomy group was 9.27% (9 cases ) and 7.92% (8 cases), respectively, the differencewas not statistically significance (χ2=0.01, P = 0.907); KPS score of laparoscopy group in 7 days after surgery were higher than laparotomy group [(79.33 ± 15.54) vs (73.49 ± 13.37), t = 2.84, P = 0.005], and in 30 days after surgery showed no statistical differences. Conclusion The clinical effect of 1aparoscopy-assisted distal gastrectomy for advanced gastric cancer is equivalent to the laparotomy, while with less trauma. Short-term quality of life in 1aparoscopy group is higher than laparotomy group.

Objective To investigate the experience of surgical treatment of primary extraperitoneal pelvic neoplasms,in order to improve tumor resection rate and safety.Methods The clinical data of 29 cases of primary extraperitoneal pelvic neoplasms were retrospectively analyzed from 1995 to 2013.To evaluate tumor resection preoperatively by CT,MRI and three dimensional reconstruction (3 d) medical technology,5 cases of preoperative interventional vascular embolization,intraoperative 2 cases in the iliac artery ligation,2 cases of intraoperative temporary blocking abdominal aorta.Intraoperative combined a variety of surgical approach to remove the tumor.Results Twenty-nine cases of patients,11 underwent tumor resection,5 underwent tumor resection and rectum resection plus sigmoid colostomy,the structure of 4 underwent tumor resection and repair damaged + sigmoid colon rectum temporary colostomy,3 underwent tumor resection and bladder partial nephrectomy,4 underwent tumor resection and uterine ovarian resection,2 underwent tumor resection + tail sacral tumor resection.25 patients recover well after the surgery,complications of 4 cases:intestinal obstruction in 2 cases respectively,pelvic abscess in 1 case,lower limb venous thrombosis in 1 case,cured by conservative and interventional therapy.No operative mortality and incidence of complications was 13.8％ (4/29).Conclusion Pelvic tumor preoperative imaging evaluation,combined incision and multi-visceral resection,fractional resection and recurrence after resection is the effective examination and treatment.