Research progress of radiation nephropathy / 中华放射医学与防护杂志

Radiotherapy is an important treatment for malignant tumors. However, it is also one cause of damage to local normal tissues, such as radiation nephropathy, which is frequently induced during the radiotherapy of abdominal and pelvic tumors. The exact pathogenesis of radiation nephropathy is still unclear and is believed to be related mainly to factors including oxidative stress, cell aging, and gene changes presently. Moreover, there is a lack of effective treatments for radiation nephropathy. With an increase in the survival of tumor patients, radiation nephropathy has received increasing attention. This article mainly reviewed the research progress of radiation nephropathy from the aspects of pathogenesis and treatments, aiming to provide a reference for the research and clinical diagnosis and treatment of radiation nephropathy.

Sleep deprivation aggravates cognitive impairment in septic rats by activating neuronal glycolytic isoenzyme PFKFB3 / 中华危重病急救医学

Objective:To evaluate the effect of sleep deprivation on cognitive function in septic rats and its relationship with neuronal glycolysis isoenzyme phosphofructokinase-2/fructose-2,?6-diphosphatase 3 (PFKFB3).Methods:Fifty-six healthy male Sprague-Dawley (SD) rats were randomly divided into 4 groups ( n = 14): control group (Con group), sepsis group (LPS group), sepsis+sleep deprivation group (LPS+SD group), sepsis+sleep deprivation+glycolysis inhibitor 3-PO treatment group (LPS+SD+3-PO group). The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) 10 mg/kg. Rats in LPS+SD group were treated with sleep deprivation using a sleep deprivation instrument 24 hours after LPS injection. The LPS+SD+3-PO group was intraperitoneally injected with LPS for 24 hours, and then injected with 3-PO 50 mg/kg, followed by sleep deprivation. Novel object recognition experiments were performed 72 hours after LPS injection. Subsequently, blood and brain tissue samples were collected. The contents of lactate (Lac), reactive oxygen species (ROS) and serum tumor necrosis factor-α(TNF-α), neuron-specific enolase (NSE), pyruvate in brain tissue were detected by enzyme-linked immunosorbent assay (ELISA). Then, the lactate/pyruvate ratio was calculated. Na +-K +-ATPase activity in brain tissue was detected by colorimetry. Morphological changes in hippocampus were detected by hematoxylin-eosin (HE) staining. And the protein expression levels of PFKFB3, ZO-1 and cleaved caspase-3 were measured by Western blotting. Results:Compared with Con group, the novel object recognition index of LPS group was decreased, the levels of NSE, TNF-α, lactate/pyruvate ratio in serum and the levels of Lac, ROS and dry-wet weight ratio in brain tissue were significantly increased, Na +-K +-ATPase activity in brain tissue was decreased, the protein expressions of PFKFB3, caspase-3 were up-regulated, ZO-1 expression was down-regulated, and the neurons in hippocampus were slightly degenerated. Compared with LPS group, the novel object recognition index of LPS+SD group was further decreased [(39.4±5.3)% vs. (54.5±7.6)%)], serum NSE, TNF-α, lactate/pyruvate ratio and brain tissue Lac, ROS, dry-wet weight ratio were further increased [NSE (μg/L): 3.21±0.42 vs. 2.55±0.36, TNF-α (ng/L): 139.4±19.7 vs. 92.2±13.5, lactate/pyruvate ratio: 29.7±5.5 vs. 19.2±4.2, Lac (μmol/g): 19.51±2.33 vs. 11.34±1.52, ROS (kU/g): 117.4±18.7 vs. 78.2±11.8, dry-wet weight ratio: (81.3±9.2)% vs. (64.3±6.6)%], and Na +-K +-ATPase activity was further decreased (mmol·L -1·h -1: 1.88±0.34 vs. 2.91±0.39), the protein expressions of PFKFB3, caspase-3 were further up-regulated and ZO-1 expression was further down-regulated (PFKFB3/β-actin: 0.80±0.11 vs. 0.45±0.07, caspase-3/β-actin: 0.71±0.09 vs. 0.37±0.05, ZO-1/β-actin: 0.31±0.05 vs. 0.61±0.08). The differences were statistically significant (all P < 0.05). HE staining showed that the degeneration of neurons in hippocampus was significantly aggravated. Compared with LPS+SD group, the novel object recognition index of LPS+SD+3-PO group was increased [(50.8±5.9)% vs. (39.4±5.3)%], NSE, TNF-α, lactate/pyruvate ratio of serum and Lac, ROS, dry-wet weight ratio of brain tissue were significantly decreased [NSE (μg/L): 2.60±0.33 vs. 3.21±0.42, TNF-α (ng/L): 103.7±18.3 vs. 139.4±19.7, lactate/pyruvate ratio: 17.4±5.1 vs. 29.7±5.5, Lac (μmol/g): 13.68±2.02 vs. 19.51±2.33, ROS (kU/g): 86.9±14.5 vs. 117.4±18.7, dry-wet weight ratio: (67.7±6.9)% vs. (81.3±9.2)%], and Na +-K +-ATPase activity was increased (mmol·L -1·h -1: 2.82±0.44 vs. 1.88±0.34). The protein expressions of PFKFB3, caspase-3 were down-regulated and ZO-1 expression was up-regulated (PFKFB3/β-actin: 0.50±0.06 vs. 0.80±0.11, caspase-3/β-actin: 0.43±0.06 vs. 0.71±0.09, ZO-1/β-actin: 0.52±0.06 vs. 0.31±0.05). The differences were statistically significant (all P < 0.05). HE staining showed that the degeneration of neurons in hippocampus was significantly improved. Conclusions:Sleep deprivation could aggravate neuroinflammation, neuronal degeneration and apoptosis in septic rats, resulting in destruction of blood-brain barrier and cognitive impairment. 3-PO treatment significantly alleviate the injury and degeneration of hippocampal neurons in septic rats, inhibit neuroinflammation and apoptosis, and improve cognitive dysfunction, which may be related to the inhibition of glycolytic isoenzyme PFKFB3.

Electroacupuncture Alleviates Functional Constipation in Mice by Activating Enteric Glial Cell Autophagy via PI3K/AKT/mTOR Signaling / 中国结合医学杂志

OBJECTIVE@#To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC).@*METHODS@#According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy.@*RESULTS@#EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (P<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (P<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (P<0.05 or P<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA.@*CONCLUSION@#EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.

Development and validation of a predictive model for the risk of positive after transperineal ultrasound-guided prostate biopsy / 中华泌尿外科杂志

Objective:To develop a nomogram to predict the probability of prostate cancer after transeperineal prostate biopsy, and verify the diagnostic efficacy and clinical applicable value of the model.Methods:The clinicopathologic data of 475 patients who underwent prostate biopsy at Yijishan Hospital of Wannan Medical College between January 2019 to August 2021 were retrospectively reviewed. Of all the patients, 367 patients from January 2019 to December 2020 were in the development cohort and 108 patients from January 2021 to August 2021 were in the validation cohort. Patients in the development cohort were (68.86±9.00) years old. The tPSA level was 13.6(8.6, 23.3)ng/ml, and Prostate Imaging Reporting and Data System (PI-RADS) score was 4(3, 4) points. Patients in the validation cohort were (68.89±8.67) years old. The tPSA was 13.1(8.7, 25.6)ng/ml, and PI-RADS score was 4 (3, 5) points. Univariate and multivariate logistic regression were used to analyze prostate cancer risk factors in the development cohort. Then the nomogram prediction model was established by the risk factors. The prediction model's performance was evaluated using receiver operating characteristic (ROC) curves, calibration maps, and decision curve (DCA) analysis in the development cohort. The performance of the model was verified in the validation cohort.Results:The pathological results showed 180 patients with prostate cancer and 187 patients without prostate cancer in the development cohort. The validation cohort included 53 patients with and 55 without prostate cancer. Based on the results of the univariate and multivariate logistic regression analysis, this model incorporates factors including age ( OR=1.059, P=0.003), platelet-to-monocyte ratio (PMR) ( OR=0.002, P=0.011), f/tPSA ( OR=0.009, P=0.020), and PI-RADS score ( OR= 3.076, P<0.001). The calibration curve revealed a great agreement. Internal validation of the nomogram showed that the area under the ROC curve was 0.845 (95% CI 0.794-0.895). The Hosmer-Lemeshow test was also performed( χ2=1.476, P=0.224). The validation group with an area under the ROC curve was 0.869 (95% CI 0.797-0.941). The results of the decision curve analysis indicated that the decision curve was located above the positive and negative lines in the threshold range of 10% to 90%, within which the model has clinical application. Conclusions:The nomogram, which combines patient age, PMR, f/t PSA, and PI-RADS scores, has high predictive efficacy for prostate cancer and has clinical application value.

Effects of melatonin preconditioning on hepatic ischemia-reperfusion injury in rats with nonalcoholic fatty liver disease / 中华麻醉学杂志

Objective:To evaluate the effect of melatonin preconditioning on hepatic ischemia-reperfusion (I/R) injury in rats with non-alcoholic fatty liver disease (NAFLD).Methods:Forty-eight SPF male Sprague-Dawley rats, aged 10-12 weeks, weighing 200-230 g, were divided into 4 groups ( n=12 each) using a random number table method: control group (Con group), NAFLD group, NAFLD + hepatic I/R group (NAFLD+ HIR group), and NAFLD + hepatic I/R + melatonin treatment group (NAFLD+ HIR+ MT group). The NAFLD model was developed by a high-fat and high-glucose diet (10% glucose, 10% fat) for 8 consecutive weeks in NAFLD, NAFLD+ HIR and NAFLD+ HIR+ M groups, and rats were fed with common chow and freely drank water in the other groups.Melatonin 10 mg/kg was given intragastrically daily for 2 consecutive weeks before developing the model in group NAFLD+ HIR+ MT.The model of liver I/R injury was developed by clipping the hepatic artery and portal vein for 20 min, opening for 5 min, and re-clamping for 20 min followed by restoration of perfusion.Blood samples from inferior vena cava were collected and liver tissues were obtained at 6 h of reperfusion to detect serum levels of insulin, blood glucose, free fatty acid (FFA), triglyceride (TG), alanine aminotransferase (ALT), aspartate amino transferase (AST) and ferritin, and insulin resistance index was calculated.The levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), reactive oxygen species (ROS) and Fe 2+ in liver tissues were detected by enzyme-linked immunosorbent assay, the pathological changes of liver tissues were examined with a light microscope after hematoxylin-eosin staining.The expression of nuclear factor E2-related factor 2 (Nrf2), lysophosphatidylcholine acyltransferase 3 (LPCAT3), long-chain fatty acyl-CoA synthase 4 (ACSL4) and glutathione peptide peroxidase 4 (GPX4) was detected by Western blot. Results:Compared with Con group, the levels of serum FFA, TG, ALT, AST and ferritin and insulin resistance index were significantly increased, the levels of ROS and Fe 2+ in liver tissues were increased, the levels of GSH-Px and SOD were decreased, the expression of ACSL4 and LPCAT3 was up-regulated, and the expression of Nrf2 and GPX4 was down-regulated in NAFLD group ( P<0.05). Compared with NAFLD group, the serum levels of FFA, TG, ALT, AST and ferritin and insulin resistance index were significantly increased, the levels of ROS and Fe 2+ were decreased, the levels of GSH-Px and SOD were increased, the expression of ACSL4 and LPCAT3 was up-regulated, and the expression of Nrf2 and GPX4 was down-regulated in NAFLD+ HIR group ( P<0.05). Compared with NAFLD+ HIR group, the serum levels of FFA, TG, ALT, AST and ferritin and insulin resistance index were significantly increased, the levels of ROS and Fe 2+ were decreased, the levels of GSH-Px and SOD were increased, the expression of ACSL4 and LPCAT3 was down-regulated, and the expression of Nrf2 and GPX4 was up-regulated in NAFLD+ HIR+ MT group ( P<0.05). Conclusions:Melatonin preconditioning can alleviate hepatic I/R injury in rats with NAFLD, and the mechanism may be related to activation of Nrf2 signaling pathway, reduction of lipid peroxidation and inhibition of ferroptosis.

Differences in organ dysfunction between gram-positive and gram-negative bacteria-induced sepsis in rats / 中华麻醉学杂志

Objective:To evaluate the differences in organ dysfunction between gram-positive and gram-negative bacteria-induced sepsis in rats.Methods:Fifty-two adult male Sprague-Dawley rats, weighing 340-380 g, aged 15-18 weeks, were divided into 3 groups using a random number table method: control group (C group, n=12), G - bacteria group ( n=20), and G + bacteria group ( n=20). The G + and G - septic models were developed by intraperitoneal injection of inactivated Staphylococcus aureus and Escherichia coli suspension in G + and G - bacteria groups, respectively.The survival status within 36 h after injection of inactivated bacteria was recorded.Mean arterial pressure (MAP), platelet count (Plt), oxygenation index (OI) and serum concentrations of tumor necrosis factor α (TNF-α), cardiac troponin T (cTnT), total bilirubin (TBIL), creatinine (Cr), neuron-specific enolase (NSE) and lactic acid (Lac) were measured at 6, 12, 24 and 36 h after injection of inactivated bacteria.Fear conditioning test and open field test were performed at 12 and 36 h after injection of inactivated bacteria.The apoptosis rate of neurons in hippocampal CA1 area was measured by TUNEL, and the permeability of blood-brain barrier was measured by Evans blue method.The histopathological changes of lung, heart, kidney and brain tissues were examined at 36 h after injection of inactivated bacteria. Results:Compared with C group, the number of crossing grids and percentage of time spent freezing were significantly decreased, the apoptosis rate of neurons and permeability of blood-brain barrier were increased, and the survival rate was decreased in G - bacteria group and G + bacteria group ( P<0.05); the serum TNF-α concentration was significantly increased in G + bacteria group, and the serum cocentration of OI was significantly decreased, and the serum concentrations of cTnT, Cr, TNF-α and Lac were increased in G - bacteria group at 6 h after injection of inactivated bacteria ( P<0.05); the serum concentrations of cTnT, Cr, NSE, TNF-α and Lac in G + bacteria group and serum concentrations of cTnT, Cr, TNF-α and Lac in G - bacteria group were increased, and the OI, MAP and Plt were decreased at 12 h after injection of inactivated bacteria in both groups ( P<0.05); the serum concentrations of cTnT, TBIL, Cr, NSE, TNF-α and Lac were increased, and OI, MAP and Plt were decreased at 24 and 36 h after injection of inactivated bacteria in G + bacteria group and G - bacteria group ( P<0.05). Compared with G + bacteria group, the serum concentrations of TNF-α and cTnT and apoptosis rate of neurons were significantly decreased at 12 h after injection ( P<0.05); the serum concentrations of TNF-α and Lac were significantly increased, the serum concentrations of cTnT, OI, MAP and Plt were decreased at 24 h after injection of inactivated bacteria ( P<0.05); the serum concentrations of Cr, NSE, TNF-α and Lac were significantly increased, OI, MAP and Plt were decreased, and the percentage of time spent freezing, apoptosis rate of neurons and permeability of blood-brain barrier were increased at 36 h after injection of inactivated bacteria in G - bacteria group ( P<0.05). Conclusions:Early respiratory dysfunction and multiple organ failure often occur in G - bacteria sepsis, while G + bacteria sepsis is more likely to cause early circulatory and neurological dysfunction, and G - sepsis presents with more serious organ damage and high fatality rate as the disease progresses.

Bioinformatics analysis identifies aging/senescence-induced genes in calcified plaques / 生理学报

Vascular calcification is an important pathophysiological basis of cardiovascular disease with its underlying mechanism unclear. In recent years, studies have shown that aging is one of the risk factors for vascular calcification. The purpose of this study was to investigate the microenvironmental characteristics of vascular calcification, identify aging/senescence-induced genes (ASIGs) closely related to calcified plaques, and explore the evolution trajectory of vascular calcification cell subsets. Based on the bioinformatics method, the single cell transcriptome sequencing data (Gene Expression Omnibus: GSE159677) of carotid artery samples from 3 patients undergoing carotid endarterectomy were grouped and annotated. Vascular calcification-related aging genes were identified by ASIGs data set. The pseudotime trend of ASIGs in cell subsets was analyzed by Monocle 3, and the evolution of vascular calcification cells was revealed. After quality control, all cells were divided into 8 cell types, including B cells, T cells, smooth muscle cells, macrophages, endothelial cells, fibroblasts, mast cells, and progenitor cells. Ten ASIGs related to vascular calcification were screened from the data set of ASIGs, which include genes encoding complement C1qA (C1QA), superoxide dismutase 3 (SOD3), lysozyme (LYZ), insulin-like growth factor binding protein-7 (IGFBP7), complement C1qB (C1QB), complement C1qC (C1QC), Caveolin 1 (CAV1), von Willebrand factor (vWF), clusterin (CLU), and αB-crystallin (CRYAB). Pseudotime analysis showed that all cell subsets were involved in the progression of vascular calcification, and these ASIGs may play an important role in cell evolution. In summary, AGIS plays an important role in the progression of vascular calcification, and these high expression genes may provide ideas for early diagnosis and treatment of vascular calcification.

Effectiveness and safety of acupuncture for treating functional constipation: An overview of systematic reviews / 中西医结合学报

BACKGROUND@#Functional constipation (FC) is one of the most prevalent functional gastrointestinal disorders. Dissatisfaction with medications prescribed to treat FC may lead patients to seek alternative treatments. Numerous systematic reviews (SRs) examining the use of acupuncture to treat FC have reported inconsistent results, and the quality of these studies has not been fully evaluated.@*OBJECTIVE@#In this overview, we evaluated and summarized clinical evidence on the effectiveness and safety of acupuncture for treating FC and evaluated the quality and bias of the SRs we reviewed.@*SEARCH STRATEGY@#The search strategy was structured by medical subject headings and search terms such as "acupuncture therapy" and "functional constipation." Electronic searches were conducted in eight databases from their inception to September 2020.@*INCLUSION CRITERIA@#SRs that investigated the effectiveness and safety of acupuncture for managing FC were included.@*DATA EXTRACTION AND ANALYSIS@#Two authors independently extracted information and appraised the methodology, reporting accuracy, quality of evidence, and risk of bias using the following critical appraisal tools: (1) A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2); (2) Risk of Bias in Systematic Reviews (ROBIS); (3) Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A); and (4) the Grading of Recommendations, Assessment, Development and Evaluations (GRADE). A κ index was used to score the level of agreement between the 2 reviewers.@*RESULTS@#Thirteen SRs that examined the clinical utility of acupuncture for treating FC were identified. Using the AMSTAR 2 tool, we rated 92.3% (12/13) of the SRs as "critically low" confidence and one study as "low" confidence. Using the ROBIS criteria, 38.5% (5/13) of the SRs were considered to have "low risk" of bias. Based on PRISMA-A, 76.9% (10/13) of the SRs had over 70% compliance with reporting standards. The inter-rater agreement was good for AMSTAR 2, ROBIS, and PRISMA-A. Using the GRADE tool, we classified 22.5% (9/40) of the measured outcomes as "moderate" quality, 57.5% (23/40) as "low" quality, and 20.0% (8/40) as "very low" quality. The inter-rater agreement was moderate when using GRADE. Descriptive analyses indicated that acupuncture was more efficacious than sham acupuncture for improving weekly complete spontaneous bowel movements (CSBMs) and for raising the Bristol Stool Form Scale (BSFS) score. Acupuncture appeared to be superior to anti-constipation drugs for improving weekly spontaneous bowel movements, the total effective rate, and the Patient Assessment of Constipation Quality of Life score. Although ten SRs mentioned the occurrence of adverse events, serious adverse events were not associated with acupuncture treatment.@*CONCLUSION@#Acupuncture may be more efficacious than sham acupuncture for improving CSBMs and BSFS scores and may be superior to anti-constipation drugs for improving bowel movement frequency, as well as quality of life. Limitations to current studies and inconsistent evidence suggest a need for more rigorous and methodologically sound SRs to draw definitive conclusions.@*SYSTEMATIC REVIEW REGISTRATION@#PROSPERO CRD42020189173.

Efficacy of bedside gastric ultrasound in guiding enteral nutrition therapy in patients with spontaneous cerebral hemorrhage / 中华麻醉学杂志

Objective:To evaluate the efficacy of bedside gastric ultrasound in guiding enteral nutrition therapy in the patients with spontaneous cerebral hemorrhage.Methods:Sixty-one patients with spontaneous intracerebral hemorrhage in the intensive care unit (ICU) of our hospital, aged 18-60 yr, with the European malnutrition risk screening score in 2002 was ≥ 3, who could not eat orally, were selected.All patients received decompression or aneurysm clipping under general anesthesia.Patients were divided into 2 groups using a random number table method: control group ( n=30) and ultrasound group ( n=31). Nutrient infusion pump was used to infuse standard whole protein formula enteral nutrition continuously through a nasogastric tube.In control group, gastric residual volume, residual traits and bowel sounds were evaluated according to gastric drainage to start or adjust enteral nutrition treatment.In ultrasound group, the antral motility index and gastric residual volume were monitored by the modified antral single section method under ultrasound to start or adjust enteral nutrition treatment.The starting time of enteral nutrition, time to reach the target feeding amount, rate of reaching the target feeding standard within 96 h, interruption of enteral nutrition, duration of hospitalization in ICU, and occurrence of intraperitoneal hypertension, aspiration, diarrhea, gastrointestinal bleeding and new pulmonary infection during enteral nutrition therapy were recorded. Results:Compared with control group, the initiation time of enteral nutrition and time to reach the target feeding amount were significantly shortened, the interruption rate of enteral nutrition was decreased, the rate of reaching the target feeding standard within 96 h was increased, the incidence of aspiration and new pulmonary infection was decreased ( P<0.05), and no significant change was found in the duration of hospitalization in ICU and incidence of intraperitoneal hypertension, diarrhea and upper gastrointestinal bleeding in ultrasound group ( P>0.05). Conclusions:Bedside gastric ultrasound-guided enteral nutrition therapy can improve the therapeutic effect with higher safety in the patients with spontaneous intracerebral hemorrhage.

Effect of chicoric acid on oxidative stress during myocardial injury in sepsis rats and relationship with Nrf2 signaling pathway / 中华麻醉学杂志

Objective:To evaluate the effect of chicoric acid on oxidative stress during myocardial injury in sepsis rats and the relationship with nuclear factor E2-related factor 2 (Nrf2) signaling pathway.Methods:Forty healthy male Sprague-Dawley rats, aged 8-12 weeks, weighing 220-250 g, were divided into 5 groups ( n=8 each) using a random number table method: control group (group C), lipopolysaccharide (LPS) group (group LPS), LPS+ chicoric acid group (group LPS+ CA), LPS+ Nrf2 inhibitor ML385 group (group LPS+ ML) and LPS+ chicoric acid+ ML385 group (group LPS+ CA+ ML). LPS 15 mg/kg was intraperitoneally injected to induce sepsis.Immediately after intraperitoneal injection of LPS, chicoric acid 10 mg/kg or ML385 15 mg/kg (in dimethyl sulfoxide) was intraperitoneally injected in group LPS+ CA and group LPS+ ML, respectively, and ML385 15 mg/kg and chicoric acid 10 mg/kg were intraperitoneally injected in LPS+ CA+ ML group.The equal volume of dimethyl sulfoxide was given instead in group C. At 48 h after establishment of the model, blood samples were collected from the aorta for measurement of concentration of serum interleukin-6 (IL-6) and the activities of lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) (by enzyme-linked immunosorbent assay). The animals were then sacrificed, and myocardial tissues were obtained for microscopic examination of pathological changes (by HE staining), for determination of activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and contents of reactive oxygen species(ROS) and iron (by colorimetry), for calculation of the ratio of oxidized nicotinamide adenine 2 nucleotides to reduced nicotinamide adenine 2 nucleotides (NAD + /NADH), and for detection of the expression of Nrf2, NADPH quinone oxidoreductase 1 (NQO1), glutathione peroxidase 4 (GPX4) and nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1) (by Western blot). Results:Compared with C group, the activities of serum LDH and CK-MB and concentration of IL-6 were significantly increased, the contents of ROS and iron and the ratio of NAD + /NADH were increased, activities of GSH-Px and SOD were decreased, expression of Nrf2, NQO1 and GPX4 was down-regulated, and NOX1 expression was up-regulated in the other four groups ( P<0.05). Compared with group LPS, the activities of serum LDH and CK-MB and concentration of IL-6 were significantly decreased, the contents of ROS and iron and the ratio of NAD + /NADH were decreased, activities of GSH-Px and SOD were increased, expression of Nrf2, NQO1 and GPX4 was up-regulated, NOX1 expression was down-regulated ( P<0.05), and the pathological changes of cardiomyocytes were significantly reduced in group LPS+ CA, and the activities of serum LDH and CK-MB and concentration of IL-6 were significantly increased, the ratio of NAD + /NADH were increased, activities of GSH-Px and SOD were decreased, expression of Nrf2, NQO1 and GPX4 was down-regulated, NOX1 expression was up-regulated ( P<0.05), and the pathological changes of cardiomyocytes were accentuated in group LPS+ ML.Compared with group LPS+ CA, the activities of serum LDH and CK-MB and concentration of IL-6 were significantly increased, the contents of ROS and iron and the ratio of NAD + /NADH were increased, activities of GSH-Px and SOD were decreased, expression of Nrf2, NQO1 and GPX4 was down-regulated, NOX1 expression was up-regulated ( P<0.05), and the pathological changes of cardiomyocytes were accentuated in group LPS+ CA+ ML. Conclusion:The mechanism by which chicoric acid reduces myocardial injury in sepsis rats may be related to activating Nrf2 signaling pathway and inhibiting oxidative stress.

Clinical therapeutic effects of intravitreal injection of Conbercept for macular edema in different types of retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To observe the therapeutic efficacy of intravitreal injection of conbercept for macular edema in different types of retinal vein occlusion(RVO).<p>METHODS: Retrospective cohort study of 79 patients 79 eyes in different types of RVO(BRVO:54; non-ischemic CRVO: 16; ischemic CRVO: 9)received intravitreal injection of conbercept. After 3mo injection of conbercept(IVIC), a pro re nata(PRN)strategy was adopted. The best-corrected visual acuity(BCVA,LogMAR)and central macular thickness(CMT)were recorded at baseline and at 1d, 1, 2, 3, 4, 5, 6mo post-treatment.<p>RESULTS: At 6mo, in different types of RVO, the BCVA were improved significantly than baseline(0.22±0.23 <i>vs</i> 0.70±0.32; 0.24±0.19 <i>vs</i> 0.73±0.27; 1.20±0.37 <i>vs </i>1.92±0.23; all <i>P</i><0.05). CMT were decreased significantly than baseline(199±27 <i>vs </i>422±162μm; 195±16 <i>vs </i>550±158μm; 231±55 <i>vs</i> 583±152μm; all <i>P</i><0.05). In three different treatment time groups, CMT in different types of RVO were decresed than the baselineat different time points after treatment(<i>P</i><0.05), and there was no difference between groups(<i>P</i>>0.05). In three different treatment time groups, BCVA in BRVO and non-iCRVO were improved than the baseline in three groups(<i>P</i><0.05), but in iCRVO there were little improved in >90d group.<p>CONCLUSION: Intravitreal injection of conbercept can effectively treat macular edema caused by RVO. Early and timely treatment of anti-VEGF may help improve and maintain the stability of long-term vision, and delayed anti-VEGF treatment may reduce the space for the improving vision.

Progresses in clinical treatment of multiple rib fractures and flail chest / 中国胸心血管外科临床杂志

@#The incidence of rib fracture in patients with chest trauma is about 70%. Simple rib fractures do not need special treatment. Multiple rib fractures and flail chest are critical cases of blunt trauma, which often cause serious clinical consequences and need to be treated cautiously. Nowadays, there is a controversy about the diagnosis and treatment of multiple rib fractures and flail chest. In the past, most of the patients were treated by non-operative treatment, and only less than 1% of the patients with flail chest underwent surgery. In recent years, studies have confirmed that surgical reduction and internal fixation can shorten the hospital stay, and reduce pain and cost for patients with flail chest, but there is still a lack of relevant clinical consensus and guidelines for diagnosis and treatment, which leads to great differences in clinical diagnosis and treatment plans. This article reviewed the treatment, surgical indications and surgical timing of multiple rib fractures and flail chest.

Effect of ferroptosis on hepatic ischemia reperfusion injury in diabetic rats model / 中华肝胆外科杂志

Objective:To investigate the effect of ferroptosis on hepatic ischemia reperfusion injury in diabetic rats model.Methods:Forty Sprague Dawley rats were randomly divided into four groups: sham operation group (Sham), hepatic ischemia reperfusion group (HIRI), diabetes mellitus group (DM), diabetes mellitus + hepatic ischemia reperfusion group (DM+ HIRI). The diabetic rat model was established by feeding the rats with high-fat and high-sugar feed for four consecutive weeks combined with intraperitoneal injection of 50 mg/kg 1% streptozotocin, and on this basis, the hepatic ischemia reperfusion injury model was established by local hepatic blood flow occlusion. ELISA assay was used to detect insulin content, liver function and serum lipid metabolism biomarkers. Chemiluminescence method was used to detect liver superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), polyunsaturated fatty acids (PUFA) and lipoxygenase (LOX-1) contents. HE staining was used to evaluate the pathological changes of liver tissue structure, and Western blotting was used to detect the ferroptosis-related protein expression of ACSL4 and GPX4.Results:Compared with Sham group, the level of fasting blood glucose, insulin, insulin resistance index, serum TC, TG and liver PUFA content of DM group were increased significantly ( P<0.05), HE staining showed there were a large number of fatty degeneration of hepatocytes in DM group, and extensive ballooning and necrosis of hepatocytes in DM+ HIRI group. Compared with HIRI group, level of serum TC, TG, ALT, AST and the liver PUFA and LOX-1 in DM+ HIRI group were significantly increased [TC (5.87±0.76) vs (1.34±0.2) mmol/L, TG (2.93±0.47) vs (0.71±0.34) mmol/L, ALT (339.5±40.09) vs (155.17±18.53) U/L, AST (325.50±37.52) vs (102.39±22.68) U/L, PUFA (21.58±3.01) vs (8.12±0.94) mg/g, LOX-1 (200.81±26.03) vs (73.34±10.66) U/m ] ( P<0.05). Compared with HIRI group, the protein expression of ACSL4 in DM+ HIRI group was up-regulated [(0.46±0.06) vs (1.02±0.11)], while the expression of GPX4 was down-regulated [(0.43±0.07) vs (0.14±0.02)] significantly ( P<0.05). Conclusion:The tolerance of DM rats to hepatic ischemia reperfusion injury was significantly reduced, which may be related to hepatic abnormal lipid metabolism and ferroptosis.

Effects of noise, bright light and mechanical stimulation on sleep, blood-brain barrier and cognitive function in septic rats / 中华危重病急救医学

Objective:To evaluate the effects of noise, bright light and mechanical stimulation on sleep, blood-brain barrier and cognitive function in septic rats.Methods:Forty male Sprague-Dawley (SD) rats were selected and intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS) was used to establish sepsis model. 0, 30, 45, 60, 75 dB noise stimulation or 0, 50, 100, 200, 400 Lux light stimulation were given to rats (all n = 4). The serum levels of cortisol and melatonin, and the cerebral content of Evans blue (EB) were measured 96 hours after the stimulation to determine the optimal intensity of intervention. The other 40 SD rats were randomly divided into control group (Con group), LPS group, noise intervention group (LPS+60 dB group), 200 Lux light intervention group (LPS+200 Lux group) and mechanical stimulation group (LPS+MS group), with 8 rats in each group. The open fields test and fear conditioning test were used to evaluate the exploratory behavior and cognitive function 96 hours after corresponding stimulation. The enzyme linked immunosorbent assay (ELISA) was used to detect cerebral level of interleukin-6 (IL-6) and serum levels of cortisol and melatonin. The blood-brain barrier integrity was assessed by EB staining. The protein levels of ZO-1, Claudin-5 and caspase-3 in the hippocampus were detected by Western blotting to assess the blood-brain barrier integrity and neuronal apoptosis. Results:Compared with 0 dB group or 0 Lux group, the serum melatonin concentration in 60 dB group and 200 Lux group were significantly reduced, while the serum cortisol concentration and cerebral EB content were significantly increased. Therefore, 60 dB noise and 200 Lux light were selected in the subsequent experiments. Compared with Con group, the horizontal score and vertical score in the open field test in LPS group were significantly decreased. There were no significant differences in the proportion of freezing time, the cerebral contents of EB and IL-6, the serum levels of melatonin and cortisol, and the hippocampal expressions of ZO-1, Claudin-5 and caspase-3. Compared with LPS group, the horizontal score, vertical score and the percentage of freezing time in LPS+60 dB group, LPS+200 Lux group and LPS+MS group were significantly reduced [horizontal score: 73.8±9.7, 80.3±9.4, 64.5±8.3 vs. 103.6±15.5; vertical score: 9.4±1.7, 11.2±1.9, 6.8±0.9 vs. 15.9±2.8; the percentage of freezing time: (45.3±4.7)%, (53.3±5.8)%, (42.1±5.1)% vs. (66.1±6.3)%], the serum level of melatonin was significantly decreased (ng/L: 53.62±6.20, 44.25±6.41, 45.33±5.84 vs. 74.39±7.54), the serum level of cortisol was significantly increased (nmol/L: 818.34±95.53, 710.04±65.41, 989.73±91.63 vs. 398.82±72.59), the levels of EB, IL-6 in the brain tissue were significantly increased [EB (μg/g): 2.80±0.35, 2.38±0.31, 3.24±0.42 vs. 1.59±0.26; IL-6 (ng/g): 31.56±4.11, 26.69±3.75, 37.47±4.56 vs. 16.28±2.69], the expressions of ZO-1 and Claudin-5 were significantly decreased (ZO-1/β-actin: 0.37±0.04, 0.32±0.05, 0.24±0.04 vs. 0.80±0.09; Claudin-5/β-actin: 0.62±0.08, 0.47±0.06, 0.35±0.05 vs. 0.97±0.20), and the expression of cleaved caspase-3 was significantly increased (caspase-3/β-actin: 0.56±0.06, 0.39±0.04, 0.72±0.12 vs. 0.20±0.03), with statistically significant differences (all P < 0.05). Conclusion:60 dB noise, 200 Lux light or mechanical stimulation for 96 hours could inhibit the secretion of serum melatonin, promote the secretion of cortisol, and activate neuroinflammation in septic rats, and lead to neuronal apoptosis in hippocampus and hyper-permeability of blood-brain barrier, which in turn could cause sleep disturbance and cognitive impairment.

Effects of sleep fragmentation on vascular cognitive impairment and relationship with central inflammation and oxidative stress in rats / 中华麻醉学杂志

Objective:To evaluate the effects of sleep fragmentation on vascular cognitive impairment (VCI) and the relationship with central inflammation and oxidative stress in rats.Methods:Forty-eight male Sprague-Dawley rats, aged 8-10 weeks, weighing 210-240 g, were divided into 4 groups ( n=12 each) by a random number table method: sham operation group (group Sham), sham operation + sleep fragmentation group (group Sham+ SF), group VCI and VCI+ sleep fragmentation group (group VCI+ SF). VCI was induced by ligating bilateral common carotid arteries of anesthetized rats.In VCI+ SF and Sham+ SF groups, the sleep fragmentation model was established starting from day 26 after inducing VCI, and the contextual fear conditioning test and open field test were performed on day 29.After the end of the contextual fear conditioning test, the contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-6) were determined by enzyme-linked immunosorbent assay, the hippocampal superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde (MDA) and iron contents were measured using microplate method, and the expression of nuclear factor-kappa B (NF-κB), caspase-3 and glutathione peroxidase 4 (GPX4) was determined using Western blot. Results:Compared with group Sham, the number of crossing lattices and standing on back legs and percentage of time spent freezing were significantly decreased, the contents of SOD and GSH-Px were decreased, the contents of MDA, IL-6, TNF-α and iron were increased, the expression of NF-κB and caspase-3 was up-regulated, and the expression of GPX4 was down-regulated in group VCI ( P<0.05). Compared with Sham+ SF and VCI groups, the number of crossing lattices and standing on back legs and percentage of time spent freezing were significantly decreased, the contents of SOD and GSH-Px were decreased, the contents of MDA, IL-6, TNF-α and iron were increased, the expression of NF-κB and caspase-3 was up-regulated, and the expression of GPX4 was down-regulated in group VCI+ SF ( P<0.05). Conclusion:Sleep fragmentation can aggravate VCI, and the mechanism may be related to the induction of central inflammation and oxidative stress, which leads to increased apoptosis and ferroptosis in hippocampal neurons of rats.

Lipidomics analysis on schisandrol B-induced liver enlargement in mice / 药学学报

Schisandrol B (SolB) is one of the active constituents from a traditional Chinese medicine Schisandra chinensis or Schisandra sphenanthera. Our previous studies found that SolB exerts hepatoprotective effects against drug-induced liver injury and promotes liver regeneration. We further found that SolB significantly induces liver enlargement but the mechanisms remain unclear. The purpose of this study was to investigate the change of lipidome in liver tissues during SolB-induced hepatomegaly. The animal experiment protocol was approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University. Serum and liver samples of male C57BL/6 mice were collected after intraperitoneal injection of SolB (100 mg·kg-1·d-1) for 5 days. Lipidomics analysis was performed using Q Exactive UHPLC-MS/MS system. The results showed that SolB significantly promoted liver enlargement in mice without liver injury and inflammation. Lipid accumulation was observed in the liver tissues after SolB treatment. Thirty-five lipids were identified with significant change and triglycerides (TG) were found to have the most significant increase in SolB-treated group, indicating the increase of energy production during SolB-induced hepatomegaly. This study reveals the impact of SolB on lipid metabolism and provides a potential explanation for liver enlargement induced by SolB.

Cupping therapy for patients with chronic urticaria: A systematic review and meta-analysis / 中西医结合学报

BACKGROUND@#Chronic urticaria (CU) is a common skin disease, which has a negative effect on quality of life. Current treatments do not fully control the symptoms of urticaria for many CU patients, thus effective and safe treatments for CU are still needed.@*OBJECTIVE@#This review aims to evaluate the effectiveness and safety of cupping therapy in patients with CU.@*SEARCH STRATEGY@#The search strategy looked for the presence of related keywords, such as "chronic urticaria" and "cupping therapy," in the title and abstract of research articles indexed in major databases. Randomized controlled trials (RCTs) were selected after querying nine electronic databases from their inception to May 2019 with the above search terms.@*INCLUSION CRITERIA@#RCTs were included if they recruited patients with CU who were intervened with dry or wet cupping. Publications could be written in Chinese or English.@*DATA EXTRACTION AND ANALYSIS@#Data were extracted, and the studies were assessed for the quality of their methodological design and risk of bias. Meta-analyses of the RCT data were conducted to assess the total effective rate of the treatment as the primary outcome. Skin disease quality of life index score, recurrence rate, and adverse events were assessed as secondary outcomes. Subgroup analyses were conducted based on different interventions.@*RESULTS@#Thirteen comparisons from 12 RCTs involving 842 participants were included. There were no significant differences between wet cupping and medications in total effective rate (n = 372; risk ratio [RR] = 1.10, 95% confidence interval [CI] 0.97 to 1.25; P = 0.14) or recurrence rate (n = 240; RR = 0.56, 95% CI 0.23 to 1.36; P = 0.20). Cupping therapy, in combination with antihistamine treatment was more efficacious than antihistamines alone, with a greater total effective rate (n = 342; RR = 1.18, 95% CI 1.01 to 1.39; P = 0.03) and lower recurrence rate (n = 342; RR = 0.52, 95% CI 0.32 to 0.84; P = 0.007). Cupping therapy combined with acupuncture was more effective than acupuncture alone (n = 156; RR = 1.25, 95% CI 1.07 to 1.46; P = 0.006). No serious adverse events were reported.@*CONCLUSION@#Wet cupping may be as effective as treatment with antihistamines. When cupping therapy is used as an adjuvant therapy to antihistamines or acupuncture, it may enhance the efficacy. Results drawn from these studies should be interpreted with caution and applied with care to clinical practice, because of the poor quality among the studies that were reviewed.@*SYSTEMATIC REVIEW REGISTRATION@#PROSPERO, CRD42019137451.

Effect of electroacupuncture on intestinal epithelial mucosal barrier function in rats with diarrhea-predominant irritable bowel syndrome / 针刺研究

OBJECTIVE: To observe the effect of electroacupuncture (EA) on intestinal epithelial mucosal barrier function in diarrhea-predominant irritable bowel syndrome(IBS-D) rats, so as to explore its mechanisms underlying improvement of IBS-D. METHODS: Forty SD rats (half male and half female) were randomly divided into control, model, EA and medication (Pinaverium Bromide, PB) groups, with 10 rats in each group. The IBS-D model was established by chronic unpredictable mild stress combined with gavage of Senna-leaf solution. EA (2 Hz/15 Hz，0.1-1 mA) was applied to unilateral "Zusanli"(ST36),"Tianshu" (ST25), "Sanyinjiao"(SP6) and "Taichong"(LR3) alternatively for 15 min, once daily for 14 days. Rats of the medication group was treated by gavage of PB (10 mL·kg-1·d-1) for 14 days. The visceral sensitivity (pain) was assessed by using the pressure threshold which the inserted rectal balloon catheter air-inflation (connected to a blood pressure gauge) induced stronger abdominal muscular contraction to force the rat's abdomen to lift the experimental stand surface. The diarrhea index was used to evaluate loose stool grade. The expression of Claudin-1 and Occludin (intestinal epithelial tight junction proteins) of colon tissue was detected by immunohistochemistry. The activity of plasma diamine oxidase (DAO) was assayed by using spectrophotometry. RESULTS: Compared with the control group, the diarrhea index and plasma DAO activity in the model group were significantly increased (P0.05). CONCLUSION: Electroacupuncture can significantly improve abdominal pain and diarrhea in IBS-D model rats, which may be closely associated with its effects in up-regulating the expression of intestinal epithelial tight junction proteins Claudin-1 and Occludin to restore the function of intestinal epithelial mucosal barrier.

Dynamic changes of cyclophosphamide-induced liver injury in mice / 药学学报

Cyclophosphamide (CPA) is one of the most commonly used alkylating agents in the treatment of malignant cancer. CPA is metabolized by cytochrome P450 enzymes into 4-hydroxycyclophosphamide in vivo which can exhibit anti-tumor activity. Metabolic activation of CPA can cause adverse reactions such as myelosuppression, cystitis, and liver injury. The aim of this study was to evaluate the dynamic changes of hepatic injury induced by CPA in mice. Male BALB/c mice were injected CPA (200 mg·kg-1) intraperitoneally. Both serum and liver samples were collected at 0, 2, 6, 12 and 24 hours after dosing. The animal experiment protocol was approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University. The results showed that hepatotoxicity was observed at 2 hours after CPA dosing, and the most serious liver injury was measured at 12 hours. The level of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malondialdehyde (MDA) was significantly increased, glutathione (GSH) level was significantly decreased, hepatocyte edema and vacuolar degeneration were widely observed in liver tissue, and began to recover 24 hours after dosing. In addition, due to oxidative stress damage caused by CPA, nuclear factor-erythroid 2-related factor 2 (NRF2) signaling pathway was activated and the mRNA and protein expression of its downstream targets such as quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate cysteine modifier subunit (GCLM) were up-regulated, which alleviated oxidative stress injury. In a summary, this study demonstrate the dynamic change of CPA-induced liver injury and the NRF2-mediated protective mechanisms, providing new insights into the CPA-induced liver injury.

Hippocampal neuronal ferroptosis involved in cognitive dysfunction in rats with sepsis-related encephalopathy through the Nrf 2/GPX4 signaling pathway / 中华危重病急救医学

Objective@#To evaluate the effects of ferroptosis in hippocampal neurons on cognitive dysfunction in rats with sepsis-associated encephalopathy (SAE) and its potential molecular mechanisms.@*Methods@#① Screening experiment of SAE modeling conditions: 42 healthy male Sprague-Dawley (SD) rats were divided into normal saline (NS) control group (n = 6) and lipopolysaccharide (LPS) 5, 15, 30 mg/kg groups (each n = 12) according to the random number table method. The SAE modeling conditions were determined by survival and the changes in mean arterial pressure (MAP) and heart rate (HR) within 72 hours, the percentage of stiffness status, the levels of serum inflammatory factors including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), neuron specific enolase (NSE, a marker of neuronal injury), serum iron and lactic acid (Lac) contents, and the morphological changes in CA1 of hippocampus after 72 hours. ② Deferoxamine (Def) intervention experiment: according to the results of screening experiments, 28 healthy male SD rats were divided into NS control group (n = 8), SAE group (n = 10) and Def+SAE group (n = 10) according to the random number table method. In the Def+SAE group, 100 mg/kg Def was injected intraperitoneally 12 hours before the modeling, once every 12 hours, with a total of 7 times; the rats in the NS control group and SAE group were injected with the same amount of NS. Then the cognitive function of rats was evaluated by fear conditioning test for the percentage of stiffness status; serum IL-6, TNF-α and NSE levels were determined by enzyme-linked immunosorbent assay (ELISA); the levels of serum Lac, serum iron and hippocampal malondialdehyde (MDA) and iron contents were determined by chemical colorimetric; the protein expressions of nuclear factor E2 related factor 2 (Nrf 2), glutathione peroxidase 4 (GPX4) and NAPDH oxidase 1 (NOX1) in hippocampus were determined by Western Blot; morphological changes in hippocampal CA1 were observed after hematoxylin and eosin (HE) staining.@*Results@#① Compared with the NS control group, intraperitoneal injection of 15 mg/kg LPS could significantly reduce the MAP and HR as time prolonged, and the reduction was most significant at 72 hours. The 72-hour survival rate was significantly reduced and cognitive function was impaired. The levels of serum IL-6, TNF-α, Lac and NSE were increased while the serum iron content was decreased significantly. The morphology of vertebral cells in hippocampal CA1 was irregular and some of the cells were obviously vacuolated. In the LPS 5 mg/kg group, there were no significant changes in vital signs, inflammation, organ function or cognitive dysfunction, while the symptoms of septic shock were apparent in the LPS 30 mg/kg group. Therefore, SAE model was reproduced by intraperitoneal injection of 15 mg/kg LPS for 72 hours. ② Compared with the NS control group, the percentage of stiffness in the SAE group was significantly reduced. The levels of serum IL-6, NSE and hippocampal MDA, iron were significantly increased. The serum iron contents and hippocampal Nrf 2 and GPX4 protein expressions were significantly reduced, while the hippocampal NOX1 protein expression was significantly increased. The morphology of vertebral cells in hippocampal CA1 was irregular and the cytoplasm was deeply stained. The results indicated that the level of oxidative stress in the hippocampus of SAE rats was increased, the neuron degenerations were obvious, and the cognitive function of rats were impaired. Compared with the SAE group, the percentage of stiffness in the Def+SAE group was significantly increased [(63.4±6.4)% vs. (47.6±6.0)%, P < 0.05]. The levels of serum IL-6, NSE, iron and hippocampal MDA, iron were significantly reduced [serum IL-6 (ng/L): 73.14±8.31 vs. 99.86±12.37, serum NSE (μg/L): 3.67±0.51 vs. 5.92±0.79, serum iron (mg/L): 68.43±8.12 vs. 134.60±15.63, hippocampal MDA (mol/g): 4.62±0.90 vs. 6.62±0.84, hippocampal iron (μg/g): 155.32±17.86 vs. 221.54±27.54, all P < 0.05]. The hippocampal protein expressions of Nrf 2 and GPX4 were significantly increased [Nrf 2/β-actin: 0.41±0.07 vs. 0.18±0.03, GPX4/β-actin: 0.74±0.09 vs. 0.40±0.06, all P < 0.05] while the hippocampal NOX1 protein expression was significantly reduced (NOX1/β-actin: 0.62±0.08 vs. 1.11±0.16, P < 0.05). The vertebral cells was significantly improved as compared with the SAE group. These findings showed that the oxidative stress level in hippocampus of the Def+SAE group was reduced, neuron degeneration was significantly alleviated, and the cognitive function of the rats was significantly improved.@*Conclusions@#The cognitive function of rats with SAE was significantly impaired, the hippocampal neurons were obviously damaged and ferroptosis was increased. Def pretreatment could significantly reduce iron deposition and ferroptosis in hippocampal neurons of SAE rats and improve cognitive dysfunction, which may be related to activation of Nrf 2/GPX4 signaling pathway.