Objective:To investigate the effect of nuclear factor E2-related factor 2 (Nrf2) protein on ferroptosis in mice with sepsis-associated liver injury (SALI).Methods:The male Sprague-Dawley (SD) mice were divided into 6 groups according to the random number table method, with 6 mice in each group. The SALI model of mice was established by cecal ligation and puncture (CLP), and the Sham group was only treated with laparotomy. CLP+Fer-1 group, CLP+Erastin group, CLP+ML385 group and CLP+Curcumin group were intraperitoneally injected with iron death inhibitor Ferrostatin-1 (Fer-1) 10 mg·kg -1·d -1, iron death activator Erastin 20 mg·kg -1·d -1, Nrf2 inhibitor ML385 30 mg·kg -1·d -1 and Nrf2 activator Curcumin 100 mg·kg -1·d -1 after CLP, respectively; Sham group and CLP group were given normal saline 10 mg·kg -1·d -1, each group was administered continuously for 10 days. Ten days after operation, the serum and liver tissues of mice were collected to detect the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, and the levels of malondialdehyde (MDA), glutathione (GSH) and Fe 2+ in liver homogenate. The pathological changes of liver tissue were observed under light microscope after hematoxylin-eosin (HE) staining. The shape and length of mitochondria in liver cells were observed under transmission electron microscope. The protein expressions of Nrf2, glutathione peroxidase 4 (GPX4) and prostaglandin-endoperoxide synthase 2 (PTGS2) in liver tissue were detected by Western blotting. Results:Compared with Sham group, the serum levels of ALT and AST in the CLP group were significantly increased; histologically, the hepatic cord was disordered, the cells were swollen and necrotic, and the length of mitochondria was significantly shortened; the levels of MDA and Fe 2+ in liver tissue increased significantly, and the content of GSH decreased significantly; the protein expressions of Nrf2 and GPX4 in liver tissue decreased, and the protein expression of PTGS2 increased significantly. Compared with CLP group, the serum levels of ALT and AST in CLP+Fer-1 group and CLP+Curcumin group were significantly decreased [ALT (U/L): 80.65±19.44, 103.45±20.52 vs. 283.50±37.12, AST (U/L): 103.33±11.90, 127.33±15.79 vs. 288.67±36.82, all P < 0.05]; microscopically, the hepatic cord was irregular, the cells were slightly swollen, and the mitochondrial length was significantly increased (μm: 1.42±0.09, 1.43±0.21 vs. 1.07±0.25, both P < 0.05); the levels of MDA and Fe 2+ in liver tissue decreased significantly, and the content of GSH increased significantly [MDA (mol/g): 0.87±0.23, 1.85±0.43 vs. 4.47±0.95, Fe 2+ (μg/g): 63.80±7.15, 67.48±6.28 vs. 134.52±14.32, GSH (mol/g): 1.95±0.29, 1.95±0.45 vs. 0.55±0.29, all P < 0.05]; the protein expressions of Nrf2 and GPX4 in liver tissue were significantly increased, and the protein expression of PTGS2 was significantly decreased (Nrf2/GAPDH: 1.80±0.28, 2.10±0.43 vs. 0.70±0.24, GPX4/GAPDH: 0.80±0.06, 0.93±0.07 vs. 0.48±0.02, PTGS2/GAPDH: 0.76±0.05, 0.84±0.01 vs. 1.02±0.09, all P < 0.05). However, the results of the above indexes in the CLP+Erastin group and CLP+ML385 group were opposite, and the serum levels of ALT and AST were significantly increased [ALT (U/L): 344.52±40.79, 321.70±21.10 vs. 283.50±37.12, AST (U/L): 333.50±27.90, 333.00±16.67 vs. 288.67±36.82, all P < 0.05]; microscopically, the arrangement of hepatic cords was disordered, the cells were obviously swollen and necrotic, and the length of mitochondria was significantly shortened (μm: 0.78±0.13, 0.67±0.07 vs. 1.07±0.25, both P < 0.05); the levels of MDA and Fe 2+ in liver tissue increased significantly, and the content of GSH decreased significantly [MDA (mol/g): 5.92±1.06, 5.62±0.56 vs. 4.47±0.95, Fe 2+ (μg/g): 151.40±8.03, 151.88±8.68 vs. 134.52±14.32, GSH (mol/g): 0.25±0.08, 0.23±0.11 vs. 0.55±0.29, all P < 0.05]; the protein expressions of Nrf2 and GPX4 in liver tissue were significantly decreased, and the protein expression of PTGS2 was significantly increased (Nrf2/GAPDH: 0.46±0.09, 0.46±0.11 vs. 0.70±0.24, GPX4/GAPDH: 0.34±0.05, 0.40±0.01 vs. 0.48±0.02, PTGS2/GAPDH: 1.24±0.13, 1.16±0.11 vs. 1.02±0.09, all P < 0.05). Conclusion:CLP-induced SALI can lead to ferroptosis in mice hepatocytes, and Nrf2 protein in liver tissue can mediate SALI by regulating ferroptosis.

Objective:To explore whether esketamine (ESK) can inhibit the proliferation and induce apoptosis of breast cancer cells, and explore the mechanism.Methods:CCK-8 assay was used to detect the inhibitory effect of ESK on the proliferation of breast cancer cells. Annexin V/PI staining was used to detect the morphological changes of cells; Apoptosis and reactive oxygen species were detected by flow cytometry. Western blot was used to detect apoptosis and pathway expression.Results:CCK-8 experiment results proved that ESK could inhibit the proliferation of breast cancer cells in a time-dependent manner. The survival rate of MDA-MB-468 cells treated with ESK at 20 μM was (35.47±2.61) %, which was statistically different from that treated with vinorelbine at the same concentration ( P<0.05). The IC50 value of ESK on MDA-MB-468 cells was (14.54±2.12) μM. After treatment with ESK, the mitochondrial membrane potential was significantly reduced. In the protein level, the expression of Cytochrome C, Bax and Caspase-3 was up-regulated, and the expression of Bcl-2 was down regulated, which induced the mitochondrial dependent apoptosis of MDA-MB-468 cells. ESK could up regulate the level of reactive oxygen species in MDA-MB-468 cells and regulate the expression of PI3K/AKT signaling pathway. Conclusions:ESK can inhibit the proliferation and migration of breast cancer cells and induce them to play a mitochondrial dependent apoptosis. Its mechanism is achieved by up regulating the level of ROS in breast cancer cells, thereby regulating the PI3K/AKT signaling pathway, which provides a theoretical basis for the development and utilization of Aln.

Objective:In order to discuss the ovulation induction effect and clinical significance of human menopausal gonadotropin (hMG) and follicle-stimulating hormone (FSH) on progestin primed ovarian stimulation (PPOS) protocol in patients with diminished ovarian reserve during in vitro fertilization (IVF) cycle. Methods:Using retrospective cohort study method, the patients with diminished ovarian reserve who received PPOS in IVF assisted reproduction in the Reproductive Medicine Center of the First Affiliated Hospital of Fujian Medical University from November 2018 to June 2020 were included, 110 cycles met requirements and were divided into FSH group (63 cycles) and hMG group (47 cycles) according to the different gonadotropin (Gn) used. General information and the outcome of IVF between the two groups were compared.Results:The total number of retrieved oocytes, M Ⅱ oocytes, fertilized oocytes, cleaved oocytes, day 3 (D3) embryos, all freezing embryo, two pronucleus (2PN) fertilization rate, the blastocyst formation rate, day 5 (D5) blastocyst rate and the utilization rate of oocytes, the biochemical pregnancy rate and the miscarriage rate had no statistical differences (all P>0.05). The rate of D3 high-quality embryos, the clinical pregnancy rate and the embryo implantation rate of FSH group were higher than those of hMG group [64.2% (111/173) vs. 50.0% (48/96), P=0.024; 45.8% (22/48) vs. 21.2% (7/33), P=0.023; 36.5% (27/74) vs. 16.7% (8/48), P=0.018] with statistical significances. Conclusion:For patients with diminished ovarian reserve, the rate of D3 high-quality embryos, the clinical pregnancy rate and the embryo implantation rate of FSH group are higher.

Objective:In order to discuss the ovulation induction effect and clinical significance of human menopausal gonadotropin (hMG) and follicle-stimulating hormone (FSH) on progestin primed ovarian stimulation (PPOS) protocol in patients with diminished ovarian reserve during in vitro fertilization (IVF) cycle. Methods:Using retrospective cohort study method, the patients with diminished ovarian reserve who received PPOS in IVF assisted reproduction in the Reproductive Medicine Center of the First Affiliated Hospital of Fujian Medical University from November 2018 to June 2020 were included, 110 cycles met requirements and were divided into FSH group (63 cycles) and hMG group (47 cycles) according to the different gonadotropin (Gn) used. General information and the outcome of IVF between the two groups were compared.Results:The total number of retrieved oocytes, M Ⅱ oocytes, fertilized oocytes, cleaved oocytes, day 3 (D3) embryos, all freezing embryo, two pronucleus (2PN) fertilization rate, the blastocyst formation rate, day 5 (D5) blastocyst rate and the utilization rate of oocytes, the biochemical pregnancy rate and the miscarriage rate had no statistical differences (all P>0.05). The rate of D3 high-quality embryos, the clinical pregnancy rate and the embryo implantation rate of FSH group were higher than those of hMG group [64.2% (111/173) vs. 50.0% (48/96), P=0.024; 45.8% (22/48) vs. 21.2% (7/33), P=0.023; 36.5% (27/74) vs. 16.7% (8/48), P=0.018] with statistical significances. Conclusion:For patients with diminished ovarian reserve, the rate of D3 high-quality embryos, the clinical pregnancy rate and the embryo implantation rate of FSH group are higher.