ObjectiveTo investigate the effect and therapeutic role of quercetin on ferroptosis in lipopolysaccharide （LPS）-induced acute kidney injury （AKI） rats based on the Kelch-like epichlorohydrin-related protein-1 （Keap1）/nuclear factor erythroid-2-related factor 2 （Nrf2）/antioxidant response element （ARE） pathway. MethodsSixty male SD rats were randomly divided into normal group， model group， quercetin high-dose （100 mg·kg^-1） and low-dose （10 mg·kg^-1） groups， ferroptosis inhibitor Ferrostatin 1 （FER1） group （5 mg·kg^-1）， and quercetin high-dose + Nrf2 inhibitor group （ML385， 30 mg·kg^-1）. Except for the normal group， the AKI rat model was established in each group by intraperitoneal injection of LPS （10 mg·kg^-1）. Following successful modeling， each treatment group received the corresponding dose of drug intervention， while the normal and model groups were administered an equal volume of normal saline. The intervention lasted for 3 weeks. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were measured biochemically to assess renal function. Serum tumor necrosis factor-α （TNF-α） and interleukin （IL）-1β and IL-6 levels were detected by enzyme-linked immunosorbent assay （ELISA）. The levels of Fe²⁺， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） in renal tissue were detected. Hematoxylin-eosin （HE）， Masson， and periodic acid-Schiff （PAS） staining were employed to observe pathological morphological changes in renal tissue. Mitochondrial morphological changes were observed using transmission electron microscopy. Reactive oxygen species （ROS） levels in renal tissue were detected by immunofluorescence （IF）. The protein and mRNA expression levels of Keap1， Nrf2， heme oxygenase-1 （HO-1）， glutathione peroxidase 4 （GPX4）， transferrin receptor （TFR1）， and kidney injury molecule-1 （KIM-1） were assessed by immunohistochemistry （IHC） and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the normal group， the model group exhibited significantly elevated serum levels of SCr， BUN， TNF-α， IL-1β， IL-6， Fe²⁺ and MDA in renal tissue， and significantly reduced SOD and GSH levels （P<0.01）. Pathological injury in renal tissue was severe， with evident mitochondrial damage characteristic of ferroptosis and a reduced mitochondrial count. ROS levels in renal tissue were significantly increased. The protein and mRNA expression levels of Keap1， TFR1， and KIM-1 in renal tissue were significantly elevated， while those of Nrf2， HO-1， and GPX4 were significantly decreased （P<0.01）. Compared with the model group， serum levels of SCr， BUN， TNF-α， IL-1β， IL-6， Fe²⁺ and MDA in renal tissue in the quercetin dosage groups and FER1 group showed varying degrees of reduction， while SOD and GSH levels were significantly increased （P<0.05）. Pathological injury in renal tissue was markedly alleviated， mitochondrial damage improved， and mitochondrial counts increased. ROS levels in renal tissue were significantly reduced. The protein and mRNA levels of Keap1， TFR1， and KIM-1 in renal tissue were significantly decreased， while those of Nrf2， HO-1， and GPX4 were significantly increased， with the most notable improvement in the high-dose quercetin group （P<0.05）. In comparison to the high-dose quercetin group， the ML385 group significantly weakened the protective effect of quercetin on AKI rats （P<0.05）. ConclusionQuercetin effectively inhibits ferroptosis， improves renal tissue injury， and repairs renal function in AKI rats， and its mechanism may be related to the activation of the Keap1/Nrf2/ARE pathway.

Objective To explore the effects of TRAF6 inhibition on autophagy,myocardial inflammation and cardiac function in septic mice.Methods Twenty-four male Kunming mice were randomly divided into 4 groups:sham,sham + C25-140(sham+C),cecal ligation and puncture(CLP),and cecal ligation and puncture+C25-140(CLP+C)group.Sham+C group and CLP+C group were intraperitoneally injected with C25-140 after operation.LVEF and LVFS were evaluated by ultrasound 24 hours after operation.Serum TNF-α and IL1-β were measured by ELISA.HE staining was used to evaluate myocardial inflammatory response.Autophagosomes and mitochondrial microstructure of cardiomyocytes were observed by transmission electron microscopy.TRAF6 mRNA in myocardial tissue was detected by qPCR.The expression of TRAF6,P62,Beclin-1 and LC3B protein was detected by W-B.The effect of C25-140 on myocardial injury in the septic mice was observed by inhibiting autophagy with 3-MA.Results Compared with the sham group,the levels of TRAF6 mRNA and TRAF6 in the myocardial tissue in the CLP group were significantly increased(P<0.05)and the serum TNF-α and IL1-β concentrations were signifi-cantly increased(P<0.05).Meanwhile,the myocardial tissue HE staining showed inflammatory cell infiltration and the LVEF and LVFS levels were significantly decreased in the CLP group(P<0.05).Compared with CLP group,the CLP+C group showed that the expression of TRAF6 mRNA and TRAF6 protein decreased(P<0.05),serum TNF-α and IL1-β decreased(P<0.05),myocardial histopathological myocardial inflammatory cell infiltration decreased,the LVEF and LVFS levels increased(P<0.05).Electron microscopy showed that the mitochondrial swelling decreased,autophagosomes increased,expression of Beclin-1 and LC3Ⅱ/Ⅰ increased,and P62 expression decreased(P<0.05).As compared with CLP+C group,the CLP+C+3-MA group showed that obvious inflamma-tory cell infiltration in the myocardial pathology and the LVEF and LVFS levels decreased after 3-MA inhibited autophagy(P<0.05).Conclusion Inhibition of TRAF6 can not only ameliorate myocardial inflammatory injury and cardiac dysfunction in septic mice,but promote the involvment of cardiomyocyte autophagy in provention from sepsis-induced myocardial injury.

OBJECTIVE To explore the action mechanism of kushenol F （KSCF） in treating ulcerative colitis （UC） in mice. METHODS The potential targets of KSCF intervening in UC were predicted with network pharmacology and molecular docking. C57BL/6J mice were randomly divided by body weight into model group， positive control group （sulfasalazine， 703 mg/kg）， KSCF group （100 mg/kg）， and normal group， with 6 mice per group. The UC model of mice was induced by dextran sulfate sodium solution. During the modeling period， the mice were given relevant medicine intragastrically， once a day， for 7 consecutive days. After the last administration， the disease activity index （DAI） of the mice was scored； the length of the mice’s colon was measured； pathological changes in the colon tissue of mice were observed； the levels of lipopolysaccharide （LPS） in serum， myeloperoxidase （MPO）， nitric oxide （NO） and superoxide dismutase （SOD） in the colon were detected in mice； the expression levels of occludin and ZO-1 in colon tissue of mice were detected； the proportions of CD3+T， CD4+T， and CD8+T lymphocytes in the spleen and the ratio of CD4+/CD8+ were detected； changes in colonic microbiota were analyzed by 16S rDNA sequencing. RESULTS Results of network pharmacology indicated that KSCF may treat UC by regulating signaling pathways such as phosphatidylinositol-3 kinase/protein kinase B （PI3K/AKT） and nuclear factor kappa B （NF- κB）. Molecular docking results showed that KSCF bound most stably with NF-κB p65 protein. Animal experiment results demonstrated that， compared with the model group， the pathological characteristics of colon tissue in mice were improved in KSCF group. DAI scores， serum levels of LPS， the levels of MPO，NF-κB p65 phosphorylation and NLRP3 protein expression in the colon， and the proportion of CD8+T lymphocytes in the spleen were reduced significantly （P＜0.05）. Body weight， SOD levels， expression levels of occludin and ZO-1 in the colon， proportions of CD3+T and CD4+T lymphocytes， and the CD4+/CD8+ ratio in the spleen were significantly increased （P＜0.05）； the abundance of Firmicutes， Actinobacteria， Akkermansia， and Lactobacillus genera were increased， while Proteobacteria decreased； the microbial community structure tended towards that of the normal group. CONCLUSIONS KSCF alleviates UC by restoring intestinal microbial imbalance， enhancing immune response， and inhibiting colonic inflammatory responses， thereby improving intestinal barrier integrity.

Objective:To investigate the prevalence and influencing factors of mild visual impairment in type 2 diabetic patients aged ≥50 years living in Funing County, Jiangsu Province.Methods:A population-based cross-sectional study was adopted.Cluster sampling was conducted among diabetic patients aged ≥50 years registered in the Chronic Disease Information Center of Funing County Center for Disease Prevention and Control from March 7th to April 20th, 2019.General information of selected patients was collected.Visual and ocular examinations on site were performed by ophthalmologists and technicians.The International Council of Ophthalmology standard for mild visual impairment, 0.3≤best corrected visual acuity<0.8 was adopted.The influencing factors of mild visual impairment were analyzed by logistic regression.This study protocol was approved by the Ethics Committee of Affiliated Hospital of Nantong University (No.2014-071).Results:Among the included 2 067 patients, 1 909 cases completed the investigation, with a response rate of 92.4%.There were 1 146 patients with mild visual impairment in at least one eye, and the prevalence of mild visual impairment was 60.00%.Among the eyes examined, 1 832 eyes were with mild visual impairment, accounting for 47.98%.Cataract (896/1 632), refractive error (515/1 632) and diabetic retinopathy (166/1 632) were the main causes of mild visual impairment in diabetic patients, accounting for 54.90%, 31.61% and 10.19%, respectively.Aging, female gender, low educational attainment, oral hypoglycemic drugs or subcutaneous insulin injection were risk factors for mild visual impairment in both eyes.Higher educational attainment, more sunshine exposure and exercise were protective factors for mild visual impairment in both eyes.Conclusions:The prevalence of mild visual impairment is relatively high in type 2 diabetic patients.Cataract surgery, correction of refractive error may help to improve mild visual impairment.Strengthening blood glucose control, more physical exercise and outdoor activities may slow the progression of mild visual impairment and prevent it from moderate and severe visual impairment.

Objective To determine the specific effect of manual removal of the placenta in the third stage of labor in the prevention of postpartum hemorrhage.Methods We searched PubMed,EMBASE,EBSCOhost databases and Chinese Academic Journal et al(inception to October August 2015).Articles database of all published.Randomized controlled trials comparing manual removal of the placenta with hands-off management inthe third stage of labor were included.Two independent reviewers assessed the included studies and extracted data.RevMan4.2 software was used for Meta-analysis.Results Six randomized controlled trials involving a total of 2 435 participants were eligible.There were five cases of cesarean section,one case of natural childbirth,and four English literatures and two Chinese literatures.Significant difference was found between manual removal of the placenta and handsoff management groups with respect to the incidence of postpartum hemorrhage.Conclusion Routine manual removal of placenta at cesarean section significantly increases perioperative blood loss.However,the effect in vaginal delivery need further research.

OBJECTIVE:To observe the clinical effect and safety of Xuebijing injection in the treatment of moderate and se-vere infection of stage Ⅲ-Ⅳ pressure ulcer. METHODS:A total of 130 cases of moderate and severe infection of stage Ⅲ-Ⅳ pres-sure ulcer admitted to our hospital from Jul. 2011 and Jun. 2016 were randomly divided into observation group and control group, with 65 cases in each group. Control group was treated with 0.5%Iodophor disinfectant to disinfect the sore surface,given wet ster-ile gauze soaked with 0.5% Iodophor disinfectant to compress sore surface for 30 min,and then given Aikangfu absorptive silver ion antibacterial healing dressing to fill wound,changed dressing after 2/3 was soaked. Observation group was additionally given Xuebijing injection 50 mL added into normal saline 100 mL intravenously for 30-40 min,2-3 times a day,for consecutive 7 days,on the basis of control group. Treatment course of both groups lasted for 4 weeks. The clinical efficacy,the score of pres-sure ulcer scale for healing(PUSH),debridement time,the time of local symptom and SIRS disappearance as well as the occur-rence of ADR were compared between 2 groups. RESULTS:The total response rate of observation group(93.85%)was signifi-cantly higher than that of control group (80.00%),and debridement time,the time of local symptom and SIRS disappearance were all significantly shorter than control group,with statistical significance(P<0.05). Before treatment,there was no statisti-cal significance in PUSH score between 2 groups (P>0.05). After 1-4 weeks of treatment,PUSH score of 2 groups was de-creased significantly compared to before treatment,and the score of observation group was significantly lower than that of con-trol group,with statistical significance(P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:For moderate and severe infection of stage Ⅲ-Ⅳ pressure ulcer,Xuebijing injection effectively reduces inflammatory exudation,improves the ab-sorption of necrotic tissue,relieves local symptom and systematic inflammatory reaction,promotes the healing of pressure ulcers and has good clinical effect and safety.

Objective:To examine the effect of penetrating humanistic care educationin to gynecological clinical practice teaching to nursing students′humanistic care ability. Methods:A total of 236 nursing students in the First Affiliated Hospital of Xi′an Jiaotong University were allocated to the experimental group ( n=123 ) with the clinical practice teaching methods, of which the core was training humanistic care ability, while the control group ( n=113) in the Second Affiliated Hospital of Xi′an Jiaotong University with the routine method, which mainly trained the operating skills. The humanistic caring ability between these two group students was compared. Results: Be-fore the internship, there was no statistical significance between the two groups (P>0. 05). After the internship, the rewere no significant difference ( P>0 . 05 ) in the scores of assisting to meet the basic needs,providing a good environment, andhelping to solve the difficulty. For the dimensions ofinfusing faith and hope,health education,humanistic and altruistic value,solving health problems scientifically,promoting emotional com-munication, and the total scale, the scores were significantly higher than those of the control group (P<0. 05). Conclusion:In the clinical practice teaching, permeating humanistic care education helps to improve the nursing students′ability of humanistic care.

Objective To determine the changes of heart structure and function in early stage after lung transplant and to study the relationship between decreased pulmonary artery pressure and changes of heart structure and function.Methods 45 cases of lung transplant recipients were included in the study,their preoperative and postoperative echocardiography data were reviewed,and the postoperative early changes of cardiac structure and function were analysed.Then,the Pearson correlation analysis was used to compare the relationships between the decrease of pulmonary artery pressure and the changes of cardiac structure and function.Results After lung transplant,pulmonary artery systolic pressure(PASP) decreased significantly [(62.3 ± 27.2) vs (36.20 ± 7.8)mm Hg,P ＜0.01],and right ventricular dimensions zoomed down,tricuspid valve and pulmonary valve regurgitation reduced,left atrial diameter (LAD) and left ventricular end-diastolic diameter (LVDD) were enlarged,stroke volume (SV) increased [(43.85 ± 14.78) vs (58.68 ± 13.85)],but left ventricular ejection fraction (LVEF) was decreased [(69.31 ± 7.50)％ vs (62.82 ± 8.12) ％],those differences above were statistically significant (P ＜ 0.05) compared with preoperative echocardiography date.Pearson linear correlation analysis show that after lung transplantation the more decreased PASP,the more increased LAD and LVDD,and the more decreased LVEF (P ＜0.05).Conclusions In early stage after lung transplant,the structure of right ventricular was quickly normalized,the function of right ventricular improved,LAD enlarged,SV increased,but left ventricular function reduced,there were a linear correlation between those changes and PASP reduced.Echocardiography has good reference value for early lung transplant patient.

Apogossypolone (ApoG2), a novel derivative of gossypol, has been shown to be a potent inhibitor of antiapoptotic Bcl-2 family proteins and to have antitumor activity in multiple types of cancer cells. Recent reports suggest that gossypol stimulates the generation of cellular reactive oxygen species (ROS) in leukemia and colorectal carcinoma cells; however, gossypol-mediated cell death in leukemia cells was reported to be ROS-independent. This study was conducted to clarify the effect of ApoG2-induced ROS on mitochondria and cell viability, and to further evaluate its utility as a treatment for nasopharyngeal carcinoma (NPC). We tested the photocytotoxicity of ApoG2 to the poorly differentiated NPC cell line CNE-2 using the ROS-generating TL/10 illumination system. The rapid ApoG2-induced cell death was partially reversed by the antioxidant N-acetyl-L-cysteine (NAC), but the ApoG2-induced reduction of mitochondrial membrane potential (MMP) was not reversed by NAC. In the presence of TL/10 illumination, ApoG2 generated massive amounts of singlet oxygen and was more effective in inhibiting cell growth than in the absence of illumination. We also determined the influence of light on the anti-proliferative activity of ApoG2 using a CNE-2-xenograft mouse model. ApoG2 under TL/10 illumination healed tumor wounds and suppressed tumor growth more effectively than ApoG2 treatment alone. These results indicate that the ApoG2-induced CNE-2 cell death is partly ROS-dependent. ApoG2 may be used with photodynamic therapy (PDT) to treat NPC.
Animals ; Antineoplastic Agents ; pharmacology ; Cell Death ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Gossypol ; analogs & derivatives ; pharmacology ; Humans ; Light ; Membrane Potential, Mitochondrial ; drug effects ; Mice ; Mice, Nude ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Transplantation ; Photochemotherapy ; Reactive Oxygen Species ; metabolism ; Singlet Oxygen ; metabolism ; Tumor Burden ; drug effects

Pancreatic stellate cell (PSC) activation in islet fibrosis of insulin-resistant rats induced by high-fat diet was investigated. After 20 weeks, the glucose infusion rate and glucose-stimulated insulin secretion in high-fat group were significantly decreased while fasting plasma glucose, fasting serum insulin, free fatty acid and the basal glucagon secretion were significantly increased compared with those parameters of the control rats (P< 0.05 or P<0.01). Activated PSC and collagen fiber ( type Ⅰ and Ⅲ) were found in islets of rats fed with high-fat. The result suggests that PSC activation, proliferation and migration to islet may contribute to islet fibrosis in insulin-resistant rats.