Objective::Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) filled an important data gap by showing a significant reduction of ischemic cardiovascular events in a ticagrelor plus aspirin cohort compared with placebo plus aspirin cohort among patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) but without a history of myocardial infarction. This study aims to evaluate the applicability of the THEMIS results in a real-world clinical setting in China.Methods::This retrospective, observational cohort study used data from the Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) study which enrolled participants who were hospitalized between November 2012 and December 2013. The 24-month cumulative incidence of major adverse cardiovascular event (MACE), major bleeding, and all-cause death in patients with T2DM and CAD (T2DM-CAD), T2DM and stable CAD (SCAD)(T2DM-SCAD), and T2DM and SCAD without prior myocardial infarction or stroke (THEMIS-like) were analyzed.Results::Data from 13,296 patients with CAD were included; the T2DM-CAD, T2DM-SCAD, and THEMIS-like cohorts comprised 3,344 (25.2%), 949 (7.1%), and 509 (3.8%) patients, respectively. The corresponding 24-month cumulative incidence of major bleeding was 38 (1.1%), 16 (1.7%), and 8 (1.6%), and that of MACEs was 250 (7.5%), 87 (9.2%), and 29 (5.7%), and all-cause death was 181 (5.4%), 84 (8.9%), 29 (5.7%), respectively. The risk of MACE in the THEMIS-like cohort was approximate to that in the THEMIS trial (7.7% vs. 8.5% in ticagrelor and placebo group, respectively). Conclusion::The incidence of MACE was substantial in the THEMIS-like cohort, suggesting that cardiovascular risk for future events correlates with the presence of cardiovascular disease across the CAD risk continuum.

Objective::Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) filled an important data gap by showing a significant reduction of ischemic cardiovascular events in a ticagrelor plus aspirin cohort compared with placebo plus aspirin cohort among patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) but without a history of myocardial infarction. This study aims to evaluate the applicability of the THEMIS results in a real-world clinical setting in China.Methods::This retrospective, observational cohort study used data from the Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) study which enrolled participants who were hospitalized between November 2012 and December 2013. The 24-month cumulative incidence of major adverse cardiovascular event (MACE), major bleeding, and all-cause death in patients with T2DM and CAD (T2DM-CAD), T2DM and stable CAD (SCAD)(T2DM-SCAD), and T2DM and SCAD without prior myocardial infarction or stroke (THEMIS-like) were analyzed.Results::Data from 13,296 patients with CAD were included; the T2DM-CAD, T2DM-SCAD, and THEMIS-like cohorts comprised 3,344 (25.2%), 949 (7.1%), and 509 (3.8%) patients, respectively. The corresponding 24-month cumulative incidence of major bleeding was 38 (1.1%), 16 (1.7%), and 8 (1.6%), and that of MACEs was 250 (7.5%), 87 (9.2%), and 29 (5.7%), and all-cause death was 181 (5.4%), 84 (8.9%), 29 (5.7%), respectively. The risk of MACE in the THEMIS-like cohort was approximate to that in the THEMIS trial (7.7% vs. 8.5% in ticagrelor and placebo group, respectively). Conclusion::The incidence of MACE was substantial in the THEMIS-like cohort, suggesting that cardiovascular risk for future events correlates with the presence of cardiovascular disease across the CAD risk continuum.

Objective: To evaluate the long-term prognosis of coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) by risk stratification with American College of Cardiology (ACC)/American Heart Association (AHA) classification of coronary lesions. Methods: Data used in this study derived from the I-LOVE-IT 2 trial. I-LOVE-IT 2 trial was a prospective, multicenter, randomized, assessor-blinded, noninferiority study. A total of 1 255 patients in I-LOVE-IT 2 trial with only one lesion and underwent biodegradable polymer drug-eluting stent implantation were included and grouped according to ACC/AHA classification of coronary lesions, namely type A/B1 lesion group (n=184), type B2 lesion group (n=457) and type C lesion group (n=614). The primary endpoint was 48-month patient-oriented composite endpoint (PoCE), a composite of all-cause mortality, all myocardial infarction, stroke, and/or any revascularization. The secondary endpoints were target lesion failure (TLF), components of PoCE, major bleeding (bleeding academic research consortium(BARC) type 3-5) and definite/probable stent thrombosis within 48 months. The incidences of endpoint events were compared in the three groups. The multivariable Cox hazard ratio model was used to analyze the independent predictors of PoCE and TLF at 48 months. Results: Incidences of PoCE at 48 months were significantly higher in patients with type C lesion compared with patients with type A/B1 (24.43%(150/614) vs. 14.13%(26/184), P<0.05) or B2 lesion (24.43%(150/614) vs. 15.97%(73/457), P<0.05). The multivariable Cox hazard ratio model showed that the type C lesion were the independent predictors of 48-month PoCE (HR=1.59, 95%CI 1.21-2.08, P<0.001) and TLF (HR=2.31, 95%CI 1.53-3.49, P<0.001). After multivariable adjustment, the HRs of PoCE for patients with type C lesion versus type A/B1 and type B2 were 1.91 (95%CI 1.25-2.92, P=0.003) and 1.64 (95%CI 1.23-2.20, P<0.001), respectively. Meanwhile, the HRs of TLF for patients with type C lesion versus type A/B1 and type B2 were 2.45 (95%CI 1.29-4.64, P=0.006) and 2.55 (95%CI 1.62-4.02, P=0.001), respectively. Conclusions The ACC/AHA classification of coronary lesions has good discrimination with long-term outcomes for CAD patients undergoing PCI. The type C lesion is associated with a worse prognosis, enough attention should be paid in these patients during routine clinical management.

To explore the effect of IL-33 on various tumor types,exogenous injection of recombinant mouse IL-33 protein (mIL-33) was used to study the efficacy of different subcutaneous tumor-bearing mouse models. In this study,mIL-33 has been found to significantly inhibit the growth of liver,lung,gastric,prostate,and colon cancers. However,the inhibition of tumor growth by mIL-33 was not completely consistent in different types of tumor. A lower dose of mIL-33 (10 μg/kg) significantly inhibited tumor growth in subcutaneous tumor-bearing mice of liver,lung,and gastric cancers,while a higher dose of mIL-33 (90 μg/kg) was required to exert the corresponding antitumor effect in subcutaneous tumor-bearing mouse models with prostate and colon cancers. In addition,the growth inhibitory effect of mIL-33 on subcutaneous tumors of colon cancer was also correlated with the duration of administration and the stage of tumor progression. The results of this study indicate that mIL-33 significantly inhibits the growth of a variety of tumors,suggesting that IL-33 might be an effective target for tumor treatment.

Ubiquitination, an essential post-transcriptional modification (PTM), plays a vital role in nearly every biological process, including development and growth. Despite its functions in plant reproductive development, its targets in rice panicles remain unclear. In this study, we used proteome-wide profiling of lysine ubiquitination in rice (O. sativa ssp. indica) young panicles. We created the largest ubiquitinome dataset in rice to date, identifying 1638 lysine ubiquitination sites on 916 unique proteins. We detected three conserved ubiquitination motifs, noting that acidic glutamic acid (E) and aspartic acid (D) were most frequently present around ubiquitinated lysine. Enrichment analysis of Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of these ubiquitinated proteins revealed that ubiquitination plays an important role in fundamental cellular processes in rice young panicles. Interestingly, enrichment analysis of protein domains indicated that ubiquitination was enriched on a variety of receptor-like kinases and cytoplasmic tyrosine and serine-threonine kinases. Furthermore, we analyzed the crosstalk between ubiquitination, acetylation, and succinylation, and constructed a potential protein interaction network within our rice ubiquitinome. Moreover, we identified ubiquitinated proteins related to pollen and grain development, indicating that ubiquitination may play a critical role in the physiological functions in young panicles. Taken together, we reported the most comprehensive lysine ubiquitinome in rice so far, and used it to reveal the functional role of lysine ubiquitination in rice young panicles.
Acetylation ; Lysine/metabolism* ; Oryza/metabolism* ; Plant Proteins/metabolism* ; Protein Interaction Maps ; Protein Processing, Post-Translational ; Proteome/metabolism* ; Ubiquitin/metabolism* ; Ubiquitination

Objective: To evaluate the long-term efficacy of a second generation biodegradable polymer sirolimus-eluting stent (EXCEL2) in treating patients with de novo coronary artery diseases. Methods: CREDIT Ⅱ trial was a prospective, multicenter, randomized, controlled study, conducted at 15 Chinese cardiac centres from November 2013 to December 2014. In this analysis, eligible patients for coronary stenting (n=419) were randomized to receive either the EXCEL2 stent (n=208) or the EXCEL stent (n=211). The primary endpoint was target lesion failure (TLF) at 3 years after PCI defined as a composite endpoints of cardiac death, target vessel myocardial infarction (TVMI), or clinically indicated target lesion revascularization (CI-TLR). Secondary endpoints included patient-oriented composite endpoint (PoCE) including all-cause death, all MI, or any revascularization at 3 years and independent components, and stent thrombosis according to Academic Research Consortium′s (ARC) definition. Results: Among 419 enrolled patients, 413 (98.6%) patients completed 3-year clinical follow-up. Compared with the EXCEL group, 3-year TLF (5.4%(11/204) vs. 11.5% (24/209), P=0.025) and PoCE (9.8% (20/204) vs. 20.1% (42/209), P=0.003) were significantly lower in the EXCEL2 group. The cumulative event rate of CI-TLR (2.0% (4/204) vs. 5.7% (12/209), P=0.042) and any revascularization (4.9% (10/204) vs. 14.4% (30/209), P=0.001) were statistically lower in the EXCEL2 group than in the EXCEL group. There were no significant difference between two groups in terms of all-cause death and all MI. Rates of stent thrombosis were low without significant difference between the two groups (EXCEL2 vs. EXCEL, 1.0% (2/204) vs. 2.9% (6/209), P=0.285). Conclusion 3-year clinical follow-up results demonstrate that EXCEL2 stents are effective and safe in treating CAD patients with de novo coronary lesions.

Objective: To explore the value of SYNTAX revascularization index (SRI) on evaluating the long-term prognosis of coronary artery disease (CAD) patients implanted with biodegradable polymer drug-eluting stents (BP-DES) and define the best threshold of SRI for predicting all-cause mortality in these patients. Methods: Data used in this study derived from the I-LOVE-IT 2 trial (evaluate safety and effectiveness of the Tivoli DES and the Firebird DES for treatment of coronary). I-LOVE-IT 2 trial was a prospective, multicenter, randomized, assessor-blinded, non-inferiority study. A total of 1 829 patients implanted with BP-DES were divided into 3 groups, namely SRI=100% group (n=963), 50%≤SRI<100% group (n=527) and SRI<50% group (n=339). The primary endpoint was 48-month patient-oriented composite endpoint (PoCE), a composite of all-cause mortality, myocardial infarction(MI), stroke, and/or any revascularization. The secondary endpoints were components of PoCE and definite/probable stent thrombosis at 48 months. The receiver operating characteristic curve was used to investigate the best cut-off point of SRI for 48-month all-cause mortality. The Cox regression analysis was used to identify independent predictors of the all-cause death and PoCE at 48 months. Results: Incidence of PoCE at 48 months was significantly lower in SRI=100% group than patients with 50%≤SRI<100%(17.34% (167/963) vs. 22.20% (117/527), P<0.05) and SRI<50% (17.34% (167/963) vs. 24.78% (84/339), P<0.05). Comparing with SRI=100% group, the patients with 50%≤SRI<100% suffered higher rates of all MI (7.78% (41/527) vs. 4.26% (41/963), P<0.05) and target vessel MI (6.45% (34/527) vs. 4.26% (41/963), P<0.05); patients with SRI<50% had higher rates of all-cause mortality (5.90% (20/339) vs. 3.12% (30/963), P<0.05) and any revascularization (14.16% (48/339) vs. 3.12% (30/963), P<0.05). The receiver operating characteristic curve analysis showed that the SRI=65% was the best cut-off point to predict the all-cause mortality at 48 months (area under the curve was 0.58, sensitive was 0.47, specificity was 0.70). Meanwhile, SRI<65% was an independent predictor of 48-month all-cause mortality (HR=2.06, 95%CI 1.25-3.38) and PoCE (HR=1.34, 95%CI 1.09-1.66). Conclusions SRI serves as a good index for predicting long-term prognosis and SRI<65% is an independent predictor of 48-month PoCE and all-cause mortality for CAD patients with BP-DES implantation. Meanwhile, SRI≥65% might be a reasonable threshold of incomplete revascularization.

Motor timing is an important part of sensorimotor control. Previous studies have shown that beta oscillations embody the process of temporal perception in explicit timing tasks. In contrast, studies focusing on beta oscillations in implicit timing tasks are lacking. In this study, we set up an implicit motor timing task and found a modulation pattern of beta oscillations with temporal perception during movement preparation. We trained two macaques in a repetitive visually-guided reach-to-grasp task with different holding intervals. Spikes and local field potentials were recorded from microelectrode arrays in the primary motor cortex, primary somatosensory cortex, and posterior parietal cortex. We analyzed the association between beta oscillations and temporal interval in fixed-duration experiments (500 ms as the Short Group and 1500 ms as the Long Group) and random-duration experiments (500 ms to 1500 ms). The results showed that the peak beta frequencies in both experiments ranged from 15 Hz to 25 Hz. The beta power was higher during the hold period than the movement (reach and grasp) period. Further, in the fixed-duration experiments, the mean power as well as the maximum rate of change of beta power in the first 300 ms were higher in the Short Group than in the Long Group when aligned with the Center Hit event. In contrast, in the random-duration experiments, the corresponding values showed no statistical differences among groups. The peak latency of beta power was shorter in the Short Group than in the Long Group in the fixed-duration experiments, while no consistent modulation pattern was found in the random-duration experiments. These results indicate that beta oscillations can modulate with temporal interval in their power mode. The synchronization period of beta power could reflect the cognitive set maintaining working memory of the temporal structure and attention.

Objective To evaluate the long?term efficacy of a second generation biodegradable polymer sirolimus?eluting stent (EXCEL2) in treating patients with de novo coronary artery diseases. Methods CREDITⅡtrial was a prospective, multicenter, randomized, controlled study, conducted at 15 Chinese cardiac centres from November 2013 to December 2014. In this analysis, eligible patients for coronary stenting (n=419) were randomized to receive either the EXCEL2 stent (n=208) or the EXCEL stent (n=211). The primary endpoint was target lesion failure (TLF) at 3 years after PCI defined as a composite endpoints of cardiac death, target vessel myocardial infarction (TVMI), or clinically indicated target lesion revascularization (CI?TLR). Secondary endpoints included patient?oriented composite endpoint (PoCE) including all?cause death, all MI, or any revascularization at 3 years and independent components, and stent thrombosis according to Academic Research Consortium＇s (ARC) definition. Results Among 419 enrolled patients, 413 (98.6%) patients completed 3?year clinical follow?up. Compared with the EXCEL group, 3?year TLF (5.4%(11/204) vs. 11.5% (24/209), P=0.025) and PoCE (9.8% (20/204) vs. 20.1% (42/209), P=0.003) were significantly lower in the EXCEL2 group. The cumulative event rate of CI?TLR (2.0% (4/204) vs. 5.7% (12/209), P=0.042) and any revascularization (4.9% (10/204) vs. 14.4% (30/209), P=0.001) were statistically lower in the EXCEL2 group than in the EXCEL group. There were no significant difference between two groups in terms of all?cause death and all MI. Rates of stent thrombosis were low without significant difference between the two groups (EXCEL2 vs. EXCEL, 1.0% (2/204) vs. 2.9% (6/209), P=0.285). Conclusion 3?year clinical follow?up results demonstrate that EXCEL2 stents are effective and safe in treating CAD patients with de novo coronary lesions.

Objective To explore the value of SYNTAX revascularization index (SRI) on evaluating the long?term prognosis of coronary artery disease (CAD) patients implanted with biodegradable polymer drug?eluting stents (BP?DES) and define the best threshold of SRI for predicting all?cause mortality in these patients. Methods Data used in this study derived from the I?LOVE?IT 2 trial (evaluate safety and effectiveness of the Tivoli DES and the Firebird DES for treatment of coronary). I?LOVE?IT 2 trial was a prospective, multicenter, randomized, assessor?blinded, non?inferiority study. A total of 1 829 patients implanted with BP?DES were divided into 3 groups, namely SRI=100% group (n=963), 50%≤SRI<100% group (n=527) and SRI<50% group (n=339). The primary endpoint was 48?month patient?oriented composite endpoint (PoCE), a composite of all?cause mortality, myocardial infarction(MI), stroke, and / or any revascularization. The secondary endpoints were components of PoCE and definite/probable stent thrombosis at 48 months. The receiver operating characteristic curve was used to investigate the best cut?off point of SRI for 48?month all?cause mortality. The Cox regression analysis was used to identify independent predictors of the all?cause death and PoCE at 48 months. Results Incidence of PoCE at 48 months was significantly lower in SRI=100% group than patients with 50%≤SRI<100%(17.34% (167/963) vs. 22.20% (117/527), P<0.05) and SRI<50% (17.34% (167/963) vs. 24.78% (84/339), P<0.05). Comparing with SRI=100% group, the patients with 50%≤SRI<100% suffered higher rates of all MI (7.78% (41/527) vs. 4.26% (41/963), P<0.05) and target vessel MI (6.45% (34/527) vs. 4.26% (41/963), P<0.05); patients with SRI<50% had higher rates of all?cause mortality (5.90% (20/339) vs. 3.12% (30/963), P<0.05) and any revascularization (14.16% (48/339) vs. 3.12% (30/963), P<0.05). The receiver operating characteristic curve analysis showed that the SRI=65% was the best cut?off point to predict the all?cause mortality at 48 months (area under the curve was 0.58, sensitive was 0.47, specificity was 0.70). Meanwhile, SRI<65% was an independent predictor of 48?month all?cause mortality ( HR=2.06, 95%CI 1.25-3.38) and PoCE ( HR=1.34, 95%CI 1.09-1.66). Conclusions SRI serves as a good index for predicting long?term prognosis and SRI<65% is an independent predictor of 48?month PoCE and all?cause mortality for CAD patients with BP?DES implantation. Meanwhile, SRI≥65% might be a reasonable threshold of incomplete revascularization.