Ethanol extract of Evodia lepta Merr. ameliorates cognitive impairment through inhibiting NLRP3 inflammasome in scopolamine-treated mice.

Evodia lepta Merr. (Evodia lepta) is a well-known traditional Chinese medicine, which has been widely used in herbal tea. We previously reported that the coumarin compounds from the root of Evodia lepta exhibited neuroprotective effects. However, whether Evodia lepta could inhibit NLRP3 inflammasome in dementia was still unknown. In this study, the components of the Evodia lepta extract were identified by HPLC-Q-TOF HRMS. We employed a scopolamine-treated mouse model. Evodia lepta extract (10 or 20 mg/kg) and donepezil were treated by gavage once a day for 14 consecutive days. Following the behavioral tests, oxidative stress levels were measured. Then, Western blot and immunofluorescence analysis were used to evaluate the expressions of NLRP3 inflammasome. 14 major components of the Evodia lepta extract were identified by HPLC-Q-TOF HRMS. The results of Morris water maze, object recognition task and open field test indicated that Evodia lepta extract could ameliorate cognitive impairment in scopolamine-treated mice. Evodia lepta extract improved cholinergic system. Moreover, Evodia lepta extract improved the expressions of PSD95 and BDNF. Evodia lepta extract suppressed neuronal oxidative stress and apoptosis. In addition, Evodia lepta extract inhibited NLRP3 inflammasome in the hippocampus of scopolamine-treated mice. Evodia lepta extract could protect against cognitive impairment by inhibiting NLRP3 inflammasome in scopolamine-treated mice.

A randomized comparison of a novel iopromide-based paclitaxel-coated balloon Shenqi versus SeQuent Please for the treatment of in-stent restenosis.

BACKGROUND: Treatment of coronary in-stent restenosis (ISR) remains challenging in contemporary clinical applications. Drug-coated balloon (DCB) angioplasty offers an effective treatment for ISR. Shenqi is a novel iopromide-based paclitaxel-coated balloon and its clinical safety, effectiveness and angiographic efficacy in patients with ISR have not been investigated. METHODS: A total of 216 subjects with the first occurrence of ISR at 11 investigational sites in China were randomly allocated in a 1:1 fashion to treatment with DCB SeQuent Please or Shenqi. Clinical follow-up was planned at 1, 6, 9 and 12 months, and angiographic follow-up was planned at 9 months. The study was powered for the primary endpoint of 9-month in-segment late loss. RESULTS: At 9-month follow-up, the in-segment late loss was 0.29 ± 0.43 mm with Shenqi versus 0.30 ± 0.46 mm with SeQuent Please, and the one-sided 97.5% upper confidence limit of the difference was 0.14 mm, achieving noninferiority of Shenqi compared with SeQuent Please (P = 0.002). In total, 12 patients developed target lesion failure (TLF) in the Shenqi group compared with 16 patients in the SeQuent Please group (10.91% versus 15.09%; P = 0.42) within 1 year. TLF was mainly driven by target lesion revascularization (9.09%) followed by target vessel-related myocardial infarction (1.82%) and cardiovascular death (0.91%) in the Shenqi group. CONCLUSIONS: Shenqi DCB was noninferior to SeQuent Please DCB for the primary endpoint of 9-month in-segment late loss. Shenqi DCB may become an attractive alternative treatment for patients with coronary ISR, withholding the need for additional stent implantation.

Clinical benefits of adjunctive tirofiban therapy in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: There is continued debate as to whether a combined reperfusion regimen with platelet glycoprotein IIb/IIIa inhibitor-tirofiban provides additional benefit in optimal myocardial reperfusion for patients with acute ST-segment elevation myocardial infarction (STEMI). This study was conducted to investigate the clinical benefits of adjunctive tirofiban therapy combined with primary percutaneous coronary intervention (PCI) in patients with STEMI. METHODS: One hundred and seventy-two consecutive patients with STEMI presented within 12 h of symptoms were randomly allocated to primary PCI combined with early (upstream group, n=57) or late administration of tirofiban (downstream group, n=57) or primary PCI treatment alone (control group, n=58). Clinical characteristics, angiographic findings, and in-hospital outcomes were compared between groups, as well as left ventricular ejection fraction (LVEF) and major adverse cardiac events (MACE, including death, reinfarction and target vessel revascularization) at 30-day and 6-month clinical follow-up. RESULTS: Despite comparable baseline clinical features among three groups, angiographic and procedural characteristics and outcomes differed significantly between patients receiving tirofiban treatment and controls, with respect to preprocedural (upstream: 28.1%, downstream: 7.0%, control: 5.2%, P<0.001) and postprocedural thrombolysis in myocardial infarction (TIMI) grade 3 flow of infarct-related artery (98.2, 94.7, 86.2%, P=0.03), TIMI myocardial perfusion grade 3 (75.4, 70.2, 53.4%, P=0.03), corrected TIMI frame count (20.4+/-5.0, 23.1+/-5.3, 32.2+/-6.7, P<0.001), resolution of the sum of ST-segment elevation (6.16+/-1.21, 6.02+/-1.09, 4.53+/-2.65 mm, P<0.001), peak value of creatine kinase-MB (218.0+/-72.5, 224.2+/-69.4, 255.3+/-77.0 ng/ml, P=0.02) and troponin I (76.0+/-21.5, 79.8+/-18.7, 86.4+/-11.0 ng/ml, P=0.007), and average hospital stay (10.6+/-5.4, 12.6+/-4.7, 14.5+/-6.5 days, P=0.001). The MACE rate at 30 days (3.5, 5.3, 15.5%, P=0.04) was reduced and LVEF (0.51+/-0.07, 0.50+/-0.07, 0.47+/-0.08, P=0.008) was higher in upstream and downstream groups than in controls. At 6-month follow-up, the MACE rate was not significantly different among groups (7.0, 8.8, 17.2%, P=0.17), but LVEF in upstream and downstream groups was significantly improved (0.59+/-0.06, 0.57+/-0.07, 0.54+/-0.07, P<0.001). Subgroup analysis demonstrated a statistically significant difference between upstream and downstream groups in preprocedural TIMI grade 3 flow (P=0.003) and postprocedural corrected TIMI frame count (P=0.007), which resulted in a shortened hospital stay (P=0.04), reduction of MACE rate at 30-day and 6-month follow-up by 34 and 20%, respectively. Multivariate logistic analysis revealed that age more than 65 years [odds ratio (OR)=3.42, P<0.01], tirofiban therapy (OR=0.56, P<0.05) and LVEF less than 0.5 during hospitalization (OR=2.56, P<0.01) were major independent predictors of MACE at 6-month clinical follow-up. No significant difference in hemorrhagic complications among three groups was noted (upstream: 10.5%, downstream: 12.3%, control: 6.9%, P=0.61). CONCLUSION: This prospective study indicates that adjunctive tirofiban therapy for patients with STEMI who undergo primary PCI can significantly improve reperfusion level in the infarct area, clinical outcomes at 30-day and 6-month follow-up, especially with upstream tirofiban therapy, and is safe.