Objective:To investigate the expression of the proinflammatory factor IL-18-mediated NOD-like receptor thermal protein domain associated protein 3/nuclear factor κB(NLRP3/NF-κB)signaling pathway in penile tissues of rats with high-fat diet-in-duced erectile dysfunction(ED),and to explore the intervention effect of sildenafil.Methods:Fifty-five sexually normal male SD rats were randomly divided into 10 cases as the normal control group,and the rest of the rats were fed with high-fat chow to establish the ED rat model,and the successfully screened ED rats were randomly divided into the ED group,the Sil group,the IL-18 group,and the IL-18+Sil group,with 8 rats in each group.Following 14 days of nonstop treatment,the morphological alterations in the penile tis-sue were observed by HE staining.Using immunohistochemistry,the amount and distribution of NF-κB p65 and Adropin in penile tis-sues were found.RT-qPCR was used to identify the expression of NLRP3 and NF-κB p65 mRNA in penile tissues.Western blot exami-nation showed the expression of the proteins NLRP3,pro-IL-18,p-NF-κB p65,NF-κB p65,and Adropin in penile tissues.Results:The ED group showed altered penis tissue morphology,destroyed muscle fibers,enlarged sinus cavity,increased mRNA and protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and pro-IL-18(all P<0.05),and decreased Adropin protein expression(P<0.05).While the protein expression of Adropin was increased(P<0.05),the mRNA and protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and pro-IL-18 in the penis tissues were decreased(all P<0.05)when compared to the ED group.The muscle fibers and sinus cav-ities of the penis were recovered to varying degrees in the Sil group.The IL-18 group experienced the destruction of muscle fibers,an enlargement of the sinus cavity,an increase in the mRNA and protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and pro-IL-18 in the penile tissues(all P<0.05),as well as a decrease in the protein expression of Adropin(P<0.05).The rat penile tissues in the IL-18+Sil group showed variable degrees of recovery in the muscle fibers and sinus cavities when compared to the IL-18 group.Ad-ditionally,there was a drop(all P<0.05)in the expressions of NLRP3,pro-IL-18 m RNA and protein,p-NF-κB p65/NF-κB p65,and p-NF-κB p65 in the penile tissues.The expression of the Adropin protein was elevated(P<0.05).Conclusion:Significant changes have been observed in the NLRP3/NF-κB signaling pathway,which is regulated by IL-18,in the hyperlipidemia ED rat model.In ED rats,sildenafil can increase erectile function by promoting the production of Adropin and blocking the activation of this pathway.

Objective:To investigate the expression of the proinflammatory factor IL-18-mediated NOD-like receptor thermal protein domain associated protein 3/nuclear factor κB(NLRP3/NF-κB)signaling pathway in penile tissues of rats with high-fat diet-in-duced erectile dysfunction(ED),and to explore the intervention effect of sildenafil.Methods:Fifty-five sexually normal male SD rats were randomly divided into 10 cases as the normal control group,and the rest of the rats were fed with high-fat chow to establish the ED rat model,and the successfully screened ED rats were randomly divided into the ED group,the Sil group,the IL-18 group,and the IL-18+Sil group,with 8 rats in each group.Following 14 days of nonstop treatment,the morphological alterations in the penile tis-sue were observed by HE staining.Using immunohistochemistry,the amount and distribution of NF-κB p65 and Adropin in penile tis-sues were found.RT-qPCR was used to identify the expression of NLRP3 and NF-κB p65 mRNA in penile tissues.Western blot exami-nation showed the expression of the proteins NLRP3,pro-IL-18,p-NF-κB p65,NF-κB p65,and Adropin in penile tissues.Results:The ED group showed altered penis tissue morphology,destroyed muscle fibers,enlarged sinus cavity,increased mRNA and protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and pro-IL-18(all P<0.05),and decreased Adropin protein expression(P<0.05).While the protein expression of Adropin was increased(P<0.05),the mRNA and protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and pro-IL-18 in the penis tissues were decreased(all P<0.05)when compared to the ED group.The muscle fibers and sinus cav-ities of the penis were recovered to varying degrees in the Sil group.The IL-18 group experienced the destruction of muscle fibers,an enlargement of the sinus cavity,an increase in the mRNA and protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and pro-IL-18 in the penile tissues(all P<0.05),as well as a decrease in the protein expression of Adropin(P<0.05).The rat penile tissues in the IL-18+Sil group showed variable degrees of recovery in the muscle fibers and sinus cavities when compared to the IL-18 group.Ad-ditionally,there was a drop(all P<0.05)in the expressions of NLRP3,pro-IL-18 m RNA and protein,p-NF-κB p65/NF-κB p65,and p-NF-κB p65 in the penile tissues.The expression of the Adropin protein was elevated(P<0.05).Conclusion:Significant changes have been observed in the NLRP3/NF-κB signaling pathway,which is regulated by IL-18,in the hyperlipidemia ED rat model.In ED rats,sildenafil can increase erectile function by promoting the production of Adropin and blocking the activation of this pathway.

Objective:To investigate the independent correlation between serum IL-6 level and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) and to evaluate its predictive value for DCI.Methods:Consecutive patients with aSAH admitted to the Affiliated Hospital of Jining Medical University from June 2017 to June 2019 were enrolled retrospectively. They were divided into DCI group and non-DCI group according to the diagnostic criteria of DCI. Multivariate logistic regression analysis was used to determine the independent correlation between serum IL-6 and DCI. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum IL-6 level for DCI. Results:A total of 160 patients with aSAH were enrolled. They aged 66.1±8.1 years, and 98 were males (61.3%); 76 patients (47.5%) had DCI. Multivariate logistic analysis showed that after adjusting for smoking, hypertension, systolic blood pressure, hyperlipidemia, and drug treatment, serum IL-6 (the first quartile as a reference, and the third quartile: odds ratio[ OR] 3.885, 95% confidence interval [ CI]1.361-7.189; the fourth quartile: OR 9.706, 95% CI 3.412-18.344), Glasgow Coma Scale score ( OR 2.174, 95% CI 1.325-4.538) and Fisher grade ( OR 3.267, 95% CI 1.638-6.725) were independently associated with DCI. The ROC curve showed that the area under the curve of serum IL-6 for predicting DCI was 0.777 (95% CI 0.706-0.849), and the optimal cut-off value was 13.01 ng/L. The sensitivity and specificity of predicting DCI were 72.4% and 71.4%, respectively. Conclusions:Serum IL-6 is an independent risk factor for DCI after aSAH, and has certain predictive value for DCI.

Objective To study effects of bivalirudin and heparin plus tirofiban on plasma P-selectin in patients with ST-segment elevation acute myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI) and compare the clinical effects on bleeding and thrombosis.Methods 260 hospitalized patients with acute STEMI who accepted emergency PCI were enrolled in the study.They were randomly divided into the bivalirudin group (129 cases) and the heparin plus tirofiban group (131 cases).Blood samples were taken before operation,during operation (about 20 minutes after medicacion injection) and after operation (three hours after the end of operation).Serum P-selectin levels were measured.All patients were followed-up for 30 days.The main events included hemorrhage within 30 days,acquired thrombocytopenia and stent thrombosis.Results The level of P-selectin increased significantly in the heparin group during operation compared to the preoperative level and remained statistically higher at three hours after the end of operation than preoperative level (P ＜ 0.05).Compared with preoperative level,the P-selectin level of the bivalirudin group was significantly lower than that of heparin group (P ＜ 0.05).After 30 days of follow-up,bivalirudin had lower rates bleeding events compared to the heparin group(5.4％ vs.15.3％,P =0.009).The need of medical intervention for bleeding events (BRAC2-5 hemorrhage) was less in the bivalirudin group(0.8％ vs.5.3％,P =0.029).There was no significant difference in the major bleeding events between the 2 groups (BRAC3-5 hemorrhage) (0 vs.0.8％,P =0.32).No significant difference found between the two groups in acquired thrombocytopenia (P ＞ 0.05).Conclusion Bivalirudin may reduce P-selectin levels in STEMI patients undergone emergency PCI during perioperative period.Heparin increases perioperative P-selectin.Bivalirudin may reduce the bleeding events.