Objective To investigate the relationship between ischemic time and thrombus types in patients with ST-segment elevation myocardial infarction (STEMI).Methods Eighty-two STEMI patients undergone emergency percutaneous coronary intervention (PCI) and coronary thrombus aspiration (CTA) from Sep.2012 to Apr.2016 were included and divided into 3 groups according to the ischemic time:≤4 hours (n=36),4-7 hours (n=30) and ＞7 hours (n=16).Visible aspirated thrombi were collected and separated into erythrocyte-rich type,platelet/fibrin-rich type and combined type thrombi by HE dying.The percentage difference of the 3 types thrombi was compared among the 3 groups.Results The percentage of platelet/fibrinrich type,erythrocyte-rich type and combined type thrombi in the 3 groups were as follows:in ≤4h group:61.1％(22/36),8.3％(3/36) and 30.6％(11/36),P=0.019;in 4-7h group:23.3％(7/30),10.0％(3/30) and 66.7％(20/30),P=0.012;and in ＞7h group:43.8％(7/16),12.5％(2/16) and 43.8％(7/16),P=0.913.For platelet/fibrin-rich type thrombi,the percentages in 3 periods were 61.1％(22/36),19.4％(7/36) and 19.4％(7/36),P=0.009;For combined type thrombi,the percentages in 3 periods were 28.9％(11/38),52.6％(20/38) and 18.4％(7/38),P=0.013;For erythrocyte-rich type thrombi,the percentages in 3 periods were 37.5％(3/8),37.5％(3/8) and 25.0％(2/8),P=0.895.Conclusions The types of intracoronary aspirated thrombi differ from various periods.Ischemia time may be an important predicted factor.

Objective To examine the influence of gender difference on the reperfusion delay in patients with ST-elevation myocardial infarction (STEMI).Methods A total of consecutive 325 patients with STEMI were analyzed admitted in the 306 Hospital of PLA from Jan.2011 to Dec.2015.Patients were divided into two groups:male group (n=268) and female group (n=57).The clinical data and the time intervals including symptom onset to first medical contact (So-to-FMC),transfer delay (FMC-to-D),FMC to balloon dilatation (FMC-to-B),activation delay and door to balloon (D-to-B) time were compared between different gender groups,and the prognosis was observed.Results The overall median of pre-hospital delay was 125 minutes.The median of prehospital delay time (male 119.5min vs.female 160.0min) and So-to-FMC time (male 69.5min vs.female 100.0min) were longer in female than in male patients,but no statistical difference existed (P＞0.05) between the two groups in pre-hospital delay,So-to-FMC,FMC-to-B,D-to-B and total ischemia time.Compared with male patients,female patients were more likely to have additional comorbidities,such as hypertension and diabetes mellitus,and lower rate of smoking (P＜0.05).However,the incidence of major adverse cardiac and cerebrovascular events (MACCE) showed no significant difference between female and male patients at 30-day (male 5.22％ vs.female 5.26％) and I-year (male 10.82％ vs.female 8.77％) follow-up (P＞0.05).Conclusion The influence of gender on reperfusion delay is gradually weakening.

Objective: To investigate the impact of symptom onset to first medical contact (SO-to-FMC)time on the prognosis of patients with acute ST-segment elevation myocardial infarction(STEMI). Methods: The clinical data of 341 consecutive STEMI patients, who were hospitalized to our hospital and received primary percutaneous coronary intervention(PCI) from August 2011 to April 2016, were retrospectively analyzed. The patients were divided into ≤90 min group (201 cases) and >90 min group (140 cases) according to the SO-to-FMC time. The treatment time, mortality and incidence of major adverse cardiac and cerebro-vascular events(MACCE) were analyzed. The risk factor of 1-year mortality after PCI and 1-year incidence of MACCE during the post-discharge follow-up period were analyzed by binary logistic regression analysis. The predictor of 4.5-year mortality after PCI was analyzed by multivariate Cox regression analysis. Methods The door to balloon time (104(88, 125) min vs. 111(92, 144)min, P=0.023), first medical contact to balloon time(146(119, 197) min vs. 177(125, 237)min, P=0.005), and symptom onset-to-balloon time(200(170, 257) min vs. 338(270, 474)min, P<0.001)were all significantly shorter in the ≤90 min group than in>90 min group. The 30-day mortality (2.99% (6/201) vs. 7.86%(11/140), P=0.042), 1-year mortality (2.89 (5/173) vs. 9.57(11/115), P=0.015), 1-year incidence of MACCE during the post-discharge follow-up period(1.16%(2/173) vs. 6.96%(8/115), P=0.021), and 4.5-year cumulative mortality(3.00% vs. 11.20%, P=0.007) after PCI were significantly lower in the ≤90 min group than in the >90 min group. Moreover, the 4.5-year incidence with free of MACCE (97.20% vs. 88.80%, P=0.025) during the post-discharge follow-up period was significantly higher in the ≤90 min group than in the >90 min group. In-hospital mortality was similar between the two groups (2.49%(5/201) vs. 6.43%(9/140), P=0.071). Results: The door to balloon time (104(88, 125) min vs. 111(92, 144)min, P=0.023) , first medical contact to balloon time(146(119, 197) min vs. 177(125, 237)min, P=0.005), and symptom onset-to-balloon time(200(170, 257) min vs. 338(270, 474)min, P<0.001) were all significantly shorter in the ≤90 min group than in >90 min group. The 30-day mortality(2.99% (6/201) vs. 7.86%(11/140), P=0.042), 1-year mortality (2.89(5/173) vs. 9.57(11/115), P=0.015), 1-year incidence of MACCE during the post-discharge follow-up period (1.16%(2/173) vs. 6.96%(8/115), P=0.021), and 4.5-year cumulative mortality (3.00% vs. 11.20%, P=0.007) after PCI were significantly lower in the ≤90 min group than in the >90 min group. Moreover, the 4.5-year incidence with free of MACCE (97.20% vs. 88.80%, P=0.025) during the post-discharge follow-up period was significantly higher in the ≤90 min group than in the >90 min group. In-hospital mortality was similar between the two groups (2.49%(5/201) vs. 6.43%(9/140), P=0.071). Results of binary logistic regression analysis showed that the SO-to-FMC time >90 min was the risk factor of 1-year mortality(OR=2.90, 95%CI 1.22-6.92, P=0.016) and 1-year incidence of MACCE (OR=5.19, 95%CI 1.21-22.20, P=0.026) during the post-discharge follow-up period. Multivariate Cox regression analysis demonstrated that the SO-to-FMC time >90 min was the risk factor of 4.5-year mortality after PCI in patients with STEMI (HR=2.88, 95%CI 1.10-7.53, P=0.031). Conclusion Shorting the SO-to-FMC time can significantly reduce the treatment time of STEMI patients, short and long-term mortalities and the incidence of MACCE, and improve the prognosis of patients with STEMI.

Objective To investigate the expression of Aspartate Beta-Hydroxylase (ASPH) in retroperitoneal liposarcoma (RL)and evaluate its clinical significances.Methods Relevant clinical data of 69 RL cases after surgical resection were collected.The expression of ASPH in tumor tissues was detected by immunohistochemistry.The CTL epitopes of ASPH protein HLA-A2 were predicted by SYFPEITHI and NetMHCpan software.Results The overall positive rate of ASPH expression for the whole group was 81％,that for well-differentiated liposarcoma was 73％,dedifferentiated liposarcoma was 87％ (P ＜ 0.05).ASPH expression was positively correlated with the postoperative recurrence free survival rate (P ＜ 0.05).Five HLA-A2 restricted CTL epitopes (9 peptides) were screened with the method of motif prediction.Conclusions ASPH expression is positively correlated with the degree of malignancy of RL,and the ASPH expression is an independent risk factor for postoperative recurrence free survival rate of RL.Moreover,ASPH was found to have 5 HLA-A2 restricted CTL epitopes,which are expected to be used for the immunotherapy of RL.

Humans ; Retroperitoneal Neoplasms ; Liposarcoma ; Calcium-Binding Proteins ; Mixed Function Oxygenases ; Membrane Proteins ; Muscle Proteins

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins