Gastric cancer (GC) is still a serious threat to human health worldwide. As a natural compound, resveratrol has been proven to have anti-tumor activity, and the nano-delivery carrier has shown its excellent ability to retain and control drug release. Res@ZIF-90 underwent synthesis via a one-pot method and subsequent characterization encompassing Dynamic Light Scattering, Scanning Electron Microscope, Transmission Electron Microscope, and UV–vis absorption spectroscope. The release of resveratrol from Res@ZIF-90 across varied pH environments were delineated employing High Performance Liquid Chromatography. The mitochondrial targeting of Res@ZIF-90 was scrutinized utilizing Fluorescent Inverted Microscopy. The cytotoxic impact of Res@ZIF-90 on HGC-27 cells was evaluated through CCK-8 assay, Live/Dead staining, scratch test, and JC-1 assay. Furthermore, the HGC-27 tumor-bearing mice model was established to explore the anti-tumor effect of Res@ZIF-90. ZIF-90 can effectively release resveratrol under acidic (pH = 5.5) conditions. In addition, Res@ZIF-90 could be taken up by cells and localized into mitochondria. ZIF-90 has no obvious cytotoxicity at the experimental concentration, while Res@ZIF-90 was more cytotoxic to HGC-27 cells than free resveratrol at the same concentration. Res@ZIF-90 significantly reduced the expressions of PGCS 1α, TFAM, PINK1, and COX IV, which together induced mitochondrial homeostasis disorders and inhibited the tumor growth of HGC-27 tumor-bearing mice in vivo. Res@ZIF-90 can inhibit the progression of gastric cancer by targeting the mitochondria of gastric cancer cells and disrupting mitochondrial homeostasis to produce cytotoxic effects. Res@ZIF-90 may be a promising antitumor drug with potential application value.

Intestinal ischemia-reperfusion injury (IRI) is a critical condition often requiring emergency intervention. Ferroptosis, a form of regulated cell death driven by phospholipid peroxidation, plays a central role in its pathogenesis. This study aimed to explore whether CoQ10 could mitigate intestinal IRI by suppressing ferroptosis. We analyzed serum CoQ10 levels and inflammatory cytokines in patients with mesenteric artery embolism. In mice, intestinal IRI was induced by transient superior mesenteric artery ligation following two weeks of CoQ10 pretreatment. Histology, ELISA, immunoblotting, and RNA sequencing were used to assess therapeutic effects. To explore mechanisms, we used CRISPR/Cas9 to generate FSP1 and COQ2 knockouts in enterocytes, along with targeted metabolomics and co-autoxidation assays. In vivo loss of FSP1 function was induced by AAV9 to evaluate its role in CoQ10-mediated protection. Utilizing both our own and publicly available intestinal IRI cohorts, we identified a correlation between elevated CoQ10 levels and reduced systemic inflammation, along with decreased oxidized lipid accumulation in ischemia-reperfusion-affected small intestines. Transcriptomic enrichment analyses and biochemical assays demonstrated that CoQ10 supplementation effectively mitigates IRI by modulating lipid metabolism and inhibiting lipid peroxidation and ferroptosis. To elucidate the mechanism of action of CoQ10 against lipid peroxidation and ferroptosis, we established an in vitro ferroptosis-associated intestinal IRI model using enterocytes, which revealed that the CoQ10-mediated suppression of ferroptosis is dependent on FSP1. Targeted metabolomics analyses and co-autoxidation assays indicated that FSP1 suppresses ferroptosis by reducing CoQ10, thereby preventing phospholipid peroxidation. Loss of function FSP1 generated by genetic and pharmacological mechanisms in enterocytes or mouse intestines led to a decrease in the levels of reduced CoQ10, negating the therapeutic effects of CoQ10 on intestinal IRI. Our study reveals a crucial role of CoQ10 in ferroptosis and highlights the potential of CoQ10 as a promising target for intestinal IRI treatment.

Aim: The reconstruction methods after proximal gastrectomy (PG) are varied but not standardized. This study was performed to evaluate the short‐term clinical outcomes between double tract reconstruction (DTR) and double flap technique (DFT).Methods: We retrospectively reviewed and collected data of patients who underwent DTR and DFT after laparoscopic proximal gastrectomy (LPG), respectively, between January 2020 and March 2023. Propensity score matching (PSM) was used to balance the baseline data of the two groups, then we compared their short‐term clinical outcomes.Results: A total of 72 patients (48 and 24 patients in the DTR and DFT groups, respectively) were included. The anastomosis time was significantly longer in the DFT group than that in the DTR group (70.1 vs. 52.7 min, p < 0.001). DFT was associated with shorter times of gas‐passing, start of diet, and postoperative length of hospital stay (p < 0.001). There were no significant differences between the two groups in terms of early and late postoperative complications (p = 0.710, p = 1.000, respectively). DFT was superior to DTR in maintaining body weight (p < 0.001), total protein (p = 0.011) and albumin levels (p = 0.018). As for QOL, DTR showed better results in the meal‐related distress subscale (p < 0.001). However, DFT was superior to DTR in terms of reducing diarrhea, constipation, and dumping related symptoms (p < 0.05).Conclusion: Double flap technique emerged as a superior alternative to DTR in terms of facilitating early postoperative recovery, sustaining nutritional status, and improving QOL. DFT could potentially be the preferred reconstruction method following laparoscopic proximal gastrectomy.

Introduction: The role of prophylactic ileostomy (PI) and its potential to reduce the risk of postoperative complications such as anastomotic leakage remains unclear. Methods: The PILLAR study (2018–2020, China, 17 centers) prospectively compared PI versus nonprophylactic ileostomy (NPI) in patients undergoing laparoscopic low anterior resection for rectal cancer. The primary endpoint was the anastomotic leakage rate. Secondary endpoints included postoperative complications, leakage management/outcomes, and leakage-associated risk factors. Results: A prospective study was conducted to gather data from 728 patients who underwent laparoscopic low anterior resection for rectal cancer, 192 (26.4%) of whom underwent PI. Seven cases of anastomotic leakage were observed in the PI group (3.6%) and 25 cases were observed in the NPI group (4.7%). Statistical analysis revealed no significant difference in the incidence of anastomotic leakage between the two groups. Moreover, the total complication rates were 17.2% in the PI group and 10.3% in the NPI group ( P = 0.012). However, the patients with anastomotic leakage in the NPI group had more severe abdominal infections, as evidenced by the C-reactive protein (CRP) values on postoperative day 5 (184.1 ± 72.2 and 77.2 ± 17.0 mg/L in the NPI and PI groups, respectively) ( P < 0.001). Patients’ postoperative procalcitonin (PCT) values similarly support this conclusion. Notably, despite this difference in infection severity, there was no statistically significant difference in the treatment or outcomes of patients with anastomotic leakage in either group. Furthermore, male sex and CRP levels on the fifth postoperative day are identified as independent risk factors for anastomotic leakage. Conclusions: PI may have failed to decrease the incidence of anastomotic leakage in patients who underwent laparoscopic low anterior resection for rectal cancer. Given the higher complication rate associated with PI, its use as a preventive measure for patients at risk of anastomotic leakage should be carefully considered.