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Abstract Background The indications, benefits, and outcomes of percutaneous transluminal renal artery intervention (PTRI) remain controversial. The study purpose was to evaluate the long-term outcomes of PTRI in clinical practice. Methods A retrospective review of 217 subjects (254 renal arteries; mean age, 59.8 years) who underwent PTRI based on medical database. Results The most common cause of renal artery stenosis was atherosclerosis in 217 (85.4%), followed by Takayasu arteritis (TA) in 23 (9.1%), fibromuscular dysplasia in five (2.0%) and others in nine (3.5%). Mean follow-up duration was 5.7 ± 3.7 years. The first restenosis rate was 7.5% (n = 19; highest in TA: n = 9, 47.4%) and second restenosis occurred in six arteries (five TAs, one fibromuscular dysplasia). Follow-up blood pressure improved from 142.0/83.5 to 122.8/73.5 mmHg (P

Abstract The benefits of intravascular ultrasonography (IVUS)-guided percutaneous coronary intervention (PCI) in the clinical context of cardiogenic shock (CS) complicating acute myocardial infarction are lacking. We aimed to investigate the impact of IVUS-guided PCI in patients with AMI and CS. From the pooled data based on a series of Korean AMI registries during 2011–2020, we identified 1418 consecutive patients who underwent PCI with second generation drug-eluting stent (DES) for AMI and CS. The primary endpoint was the 1-year rate of target lesion failure (TLF), defined as the composite of cardiac death, target vessel myocardial infarction, and ischemic-driven target lesion revascularization. In total, 294 (20.7%) and 1124 (79.3%) underwent IVUS-guided and angiography-guided PCI with second generation DES implantation, respectively. The 1-year TLF was not significantly different between groups after IPTW analysis (hazard ratio 0.93, 95% confidence interval 0.65–1.34, p = 0.70). Additionally, the adjusted landmark analysis for TLF at 30 days and between 30 days and 1 year after PCI demonstrated no significant difference between the groups. In conclusion, in patients with AMI and CS who underwent PCI with second-generation DES, IVUS-guided PCI did not improve the 1-year TLF compared with angiography-guided PCI. Registration: URL: http://cris.nih.go.kr . KCT0000863 and KCT0008355.

Abstract The long-term outcome of first-line moderate-intensity statin with ezetimibe combination therapy for secondary prevention after percutaneous coronary intervention in patients with acute coronary syndrome (ACS) compared to high-intensity statin monotherapy remains elusive. The objective of this study was to compare the effectiveness of moderate-intensity statin and ezetimibe combination therapy with high-intensity statin monotherapy. We conducted a nationwide, population-based, retrospective, cohort study of patients with ACS from 2013 to 2019. The patients using combination therapy were matched (1:1) to those using monotherapy. The primary outcome was a composite of myocardial infarction, stroke and all-cause mortality. We estimated the hazard ratios (HR) and 95% confidence intervals (CIs) using the Cox proportional hazards regression. After propensity score matching, 10,723 pairs were selected. Men accounted for 70% of the patients and 37% aged > 70 years. The primary endpoint occurred in 1297 patients (12.1%) in the combination group and in 1426 patients (13.3%) in the monotherapy group, and decreased risk (HR 0.85, 95% CI 0.78–0.92, P

Abstract We aimed to evaluate sex differences in the effects of moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg plus ezetimibe) versus high-intensity statin (rosuvastatin 20 mg) monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD). This was a sex-specific subgroup analysis of the RACING trial that evaluated the interaction between sex and treatment strategies for the primary outcome (composite of cardiovascular death, major cardiovascular events, or nonfatal stroke at 3 years). Of 3780 patients in the RACING trial, 954 (25.2%) were women. Regardless of sex, the effect of moderate-intensity statin with ezetimibe combination therapy on primary outcome compared with high-intensity statin monotherapy was similar (hazard ratio [HR] 0.98 [0.63–1.52] in women; HR 0.90 [0.71–1.14] in men). The rate of discontinuation or dose reduction of study drugs due to intolerance was lower in the ezetimibe combination group than in the high-intensity statin monotherapy group in both women (4.5% vs. 8.6%, P = 0.014) and men (4.8% vs. 8.0%, P

Background/Aims Little attention is paid to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in Korea due to the rarity of the disease. With its rising incidence, we aimed to evaluate recent changes in treatment patterns and survival outcomes of patients with CLL/SLL. Methods A total of 141 patients diagnosed with CLL/SLL between January 2010 and March 2020 who received systemic therapy were analyzed in this multicenter retrospective study. Results The median patient age was 66 years at diagnosis, and 68.1% were male. The median interval from diagnosis to initial treatment was 0.9 months (range: 0–77.6 months), and the most common treatment indication was progressive marrow failure (50.4%). Regarding first-line therapy, 46.8% received fludarabine, cyclophosphamide, plus rituximab (FCR), followed by chlorambucil (19.9%), and obinutuzumab plus chlorambucil (GC) (12.1%). The median progression-free survival (PFS) was 49.3 months (95% confidence interval [CI], 32.7–61.4), and median overall survival was not reached (95% CI, 98.4 mo–not reached). Multivariable analysis revealed younger age (≤ 65 yr) (hazard ratio [HR], 0.46; p < 0.001) and first-line therapy with FCR (HR, 0.64; p = 0.019) were independently associated with improved PFS. TP53 aberrations were observed in 7.0% (4/57) of evaluable patients. Following reimbursement, GC became the most common therapy among patients over 65 years and second in the overall population after 2017. Conclusions Age and reimbursement mainly influenced treatment strategies. Greater effort to apply risk stratifications into practice and clinical trials for novel agents could help improve treatment outcomes in Korean patients.

Abstract Regarding stent expansion indices, previous optical coherence tomography (OCT) studies have shown minimal stent area (MSA) to be most predictive of adverse events. We sought to evaluate the impact of various stent expansion and apposition indices by post-stent OCT on clinical outcomes and find OCT-defined optimal stent implantation criteria. A total of 1071 patients with 1123 native coronary artery lesions treated with new-generation drug-eluting stents with OCT guidance and final post-stent OCT analysis were included. Several stent expansion indices (MSA, MSA/average reference lumen area, MSA/distal reference lumen area, mean stent expansion, and stent expansion by linear model [stent volume/adaptive reference lumen volume]) were evaluated for their association with device-oriented clinical endpoints (DoCE) including cardiac death, target vessel-related myocardial infarction (MI) or stent thrombosis, and target lesion revascularization. MSA was negatively correlated with the risk of DoCE (hazard ratio [HR] 0.80 [0.68‒0.94]). However, stent expansion by linear model representing the overall volumetric stent expansion was associated with greater risk of DoCE (HR 1.02 [1.00‒1.04]). As categorical criteria, MSA

Single-cell C4 (SCC4) plants with bienertioid anatomy carry out photosynthesis in a single cell. Chloroplast movement is the underlying phenomenon, where chloroplast unusual positioning 1 (CHUP1) plays a key role. This study aimed to characterize CHUP1 and CHUP1-like proteins in an SCC4 photosynthetic plant, Bienertia sinuspersici. Also, a comparative analysis of SCC4 CHUP1 was made with C3, C4, and CAM model plants including an extant basal angiosperm, Amborella. The CHUP1 gene exists as a single copy from the basal angiosperms to SCC4 plants. Our analysis identified that Chenopodium quinoa, a recently duplicated allotetraploid, has two copies of CHUP1. In addition, the numbers of CHUP1-like and its associated proteins such as CHUP1-like_a, CHUP1-like_b, HPR, TPR, and ABP varied between the species. Hidden Markov Model analysis showed that the gene size of CHUP1-like_a and CHUP1-like_b of SCC4 species, Bienertia, and Suaeda were enlarged than other plants. Also, we identified that CHUP1-like_a and CHUP1-like_b are absent in Arabidopsis and Amborella, respectively. Motif analysis identified several conserved and variable motifs based on the orders (monocot and dicot) as well as photosynthetic pathways. For instance, CAM plants such as pineapple and cactus shared certain motifs of CHUP1-like_a irrespective of their distant phylogenetic relationship. The free ratio model showed that CHUP1 maintained purifying selection, whereas CHUP1-like_a and CHUP1-like_b have adaptive functions between SCC4 plants and quinoa. Similarly, rice and maize branches displayed functional diversification on CHUP1-like_b. Relative gene expression data showed that during the subcellular compartmentalization process of Bienertia, CHUP1 and actin-binding proteins (ABP) genes showed a similar pattern of expression. Altogether, the results of this study provide insight into the evolutionary and functional details of CHUP1 and its associated proteins in the development of the SCC4 system in comparison with other C3, C4, and CAM model plants.

Abstract Background Recent studies have reported improved diastolic function in patients administered sodium-glucose cotransporter 2 inhibitors (SGLT2i). We aimed to investigate the effect of dapagliflozin on left ventricular (LV) diastolic function in a diabetic animal model and to determine the molecular and cellular mechanisms underlying its function. Methods A total of 30 male New Zealand white rabbits were randomized into control, diabetes, or diabetes+dapagliflozin groups (n = 10/per each group). Diabetes was induced by intravenous alloxan. Cardiac function was evaluated using echocardiography. Myocardial samples were obtained for histologic and molecular evaluation. For cellular evaluation, fibrosis-induced cardiomyoblast (H9C2) cells were obtained, and transfection was performed for mechanism analysis (serum and glucocorticoid-regulated kinase 1 (SGK1) signaling analysis). Results The diabetes+dapagliflozin group showed attenuation of diastolic dysfunction compared with the diabetes group. Dapagliflozin inhibited myocardial fibrosis via inhibition of SGK1 and epithelial sodium channel (ENaC) protein, which was observed both in myocardial tissue and H9C2 cells. In addition, dapagliflozin showed an anti-inflammatory effect and ameliorated mitochondrial disruption. Inhibition of SGK1 expression by siRNA decreased and ENaC and Na+/H+ exchanger isoform 1 (NHE1) expression was confirmed as significantly reduced as siSGK1 in the diabetes+dapagliflozin group. Conclusions Dapagliflozin attenuated left ventricular diastolic dysfunction and cardiac fibrosis via regulation of SGK1 signaling. Dapagliflozin also reduced macrophages and inflammatory proteins and ameliorated mitochondrial disruption.

Abstract The complex structure of the left atrial appendage (LAA) brings limitations to the two-dimensional-based LAA occlusion (LAAO) size prediction system using transesophageal echocardiography. The LAA anatomy can be evaluated more precisely using three-dimensional images from cardiac computed tomography (CT); however, there is lack of data regarding which parameter to choose from CT-based images during pre-procedural planning of LAAO. We aimed to assess the accuracy of measurements derived from cardiac CT images for selecting LAAO devices. We retrospectively reviewed 62 patients with Amplatzer Cardiac Plug and Amulet LAAO devices who underwent implantation from 2017 to 2020. The minimal, maximal, average, area-derived, and perimeter-derived diameters of the LAA landing zone were measured using CT-based images. Predicted device sizes using sizing charts were compared with actual successfully implanted device sizes. The mean size of implanted devices was 27.1 ± 3.7 mm. The perimeter-derived diameter predicted device size most accurately (mean error = − 0.8 ± 2.4 mm). All other parameters showed significantly larger error (mean error; minimal diameter = − 4.9 ± 3.3 mm, maximal diameter = 1.0 ± 2.9 mm, average diameter = − 1.6 ± 2.6 mm, area-derived diameter = − 2.0 ± 2.6 mm) than the perimeter-derived diameter (all p for difference

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare but severe adverse effect that can occur as a result of bisphosphonate treatment. This study aimed to examine the relationship between PPARγ and PPARGC1A polymorphisms and the BRONJ development in female osteoporosis patients undergoing bisphosphonate treatment. We prospectively conducted this nested case–control study at the Ewha Womans University Mokdong Hospital between 2014 and 2018. We assessed five single-nucleotide polymorphisms (SNPs) of PPARγ and six SNPs of PPARGC1A and performed a multivariable logistic regression analysis to determine the independent risk factors for developing BRONJ. There were a total of 123 patients included in this study and 56 patients (45.5%) developed BRONJ. In the univariate analysis, PPARGC1A rs2946385 and rs10020457 polymorphisms were significantly associated with BRONJ (p = 0.034, p = 0.020, respectively), although the results were not statistically significant in the multivariable analysis. Patients with the combined genotypes of GG in both PPARγ rs1151999 and PPARGC1A rs2946385 showed a 3.03-fold higher risk of BRONJ compared to individuals with other genotype combinations after adjusting for confounders (95% confidence interval (CI): 1.01–9.11). Old age (≥70 years) and duration of bisphosphonate use (≥60 months) increased the risk of BRONJ. The area under the receiver operating characteristic curve for the predicted probability was 0.78 (95% CI: 0.69–0.87, p < 0.001), demonstrating a satisfactory level of discriminatory power. Our study elucidated that PPARγ and PPARGC1A polymorphisms were interactively associated with BRONJ development. These results have potential implications for tailoring personalized treatments for females undergoing bisphosphonate therapy for osteoporosis.

Abstract We investigated the impact of pre-percutaneous coronary intervention (pre-PCI) thrombolysis in myocardial infarction (TIMI) flow grade (pre-TIMI) on 3-month (3-mo) and 12-mo of dual antiplatelet therapy (DAPT) in patients with acute myocardial infarction (AMI). This was a post hoc analysis of the TICO trial. A total of 2083 patients with AMI (pre-TIMI 0/1: n = 1143; pre-TIMI 2/3: n = 940) were evaluated. The primary outcome was the occurrence of net adverse clinical events (NACE), defined as a composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events (MACCE) within 12-mo following PCI. The secondary outcomes were the occurrence of the individual components of TIMI bleedings and MACCE. In the pre-TIMI 0/1 group, the primary and second outcomes were not significantly different between the 3-mo and 12-mo DAPT groups. However, in the pre-TIMI 2/3 group, the occurrences of TIMI minor (adjusted hazard ratio [aHR]: 0.294; p = 0.016) and major or minor bleeding (aHR: 0.483; p = 0.014) on intention-to-treat analysis were significantly higher in the 12-mo than in the 3-mo DAPT group. The occurrence of MACCE was similar between the two groups. A higher bleeding tendency in 12-mo DAPT compared with 3-mo DAPT was more obvious in the pre-TIMI 2/3 group than in the pre-TIMI 0/1 group. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02494895.

Abstract We investigated the effects of stent generation on 2-year clinical outcomes between prediabetes and diabetes patients after acute myocardial infarction (AMI). A total of 13,895 AMI patients were classified into normoglycemia (group A: 3673), prediabetes (group B: 5205), and diabetes (group C: 5017). Thereafter, all three groups were further divided into first-generation (1G)-drug-eluting stent (DES) and second-generation (2G)-DES groups. Patient-oriented composite outcomes (POCOs) defined as all-cause death, recurrent myocardial infarction (Re-MI), and any repeat revascularization were the primary outcome. Stent thrombosis (ST) was the secondary outcome. In both prediabetes and diabetes groups, the cumulative incidences of POCOs, any repeat revascularization, and ST were higher in the 1G-DES than that in the 2G-DES. In the diabetes group, all-cause death and cardiac death rates were higher in the 1G-DES than that in the 2G-DES. In both stent generations, the cumulative incidence of POCOs was similar between the prediabetes and diabetes groups. However, in the 2G-DES group, the cumulative incidences of Re-MI and all-cause death or MI were significantly higher in the diabetes group than that in the prediabetes group. To conclude, 2G-DES was more effective than 1G-DES in reducing the primary and secondary outcomes for both prediabetes and diabetes groups.

Background/Aims The prognosis of small cell lung cancer (SCLC) is still poor because of rapid recurrence, despite good response to initial chemotherapy. Additionally, patients’ old ages and comorbidities are often obstacles that make it difficult to apply subsequent treatment after initial treatment. This retrospective study analyzed the correlation of post-progression survival (PPS) with overall survival (OS), and prognostic factors including comorbidities to figure out impact of subsequent chemotherapy on OS in elderly extensive disease SCLC. Methods We analyzed 101 patients of age 65 years or older who were recently diagnosed with extensive disease SCLC (ED-SCLC) in Korea University Medical Center between January 1995 and December 2015. The degree of comorbidity was scored using simplified comorbidity score (SCS). Correlation between PPS, progression-free survival (PFS) and OS was analyzed using a Pearson correlation coefficient. Cox proportional hazards regression was employed to examine the influence of clinical variables on survival. Results Median age of patients was 71 years old (range, 65 to 83). Median OS was 8.7 months (range, 0.3 to 42.7). PPS was a reliable factor on OS than PFS (R2 = 0.852, p < 0.001). Prognostic factors associated with improved survival were SCS < 9, administration > 4 cycles of first line chemotherapy and subsequent second line chemotherapy. Conclusions PPS was more correlated with OS than PFS in elderly patients with ED-SCLC. The most important prognostic factors for PPS and OS included SCS and second line chemotherapy. Patients receiving subsequent treatment had increased OS regardless of degree of comorbidity.

Abstract Machine learning approaches using intravascular optical coherence tomography (OCT) to predict fractional flow reserve (FFR) have not been investigated. Both OCT and FFR data were obtained for left anterior descending artery lesions in 125 patients. Training and testing groups were partitioned in the ratio of 5:1. The OCT-based machine learning-FFR was derived for the testing group and compared with wire-based FFR in terms of ischemia diagnosis (FFR ≤ 0.8). The OCT-based machine learning-FFR showed good correlation (r = 0.853, P

Abstract Background Head and neck cancer (HNCA) survivors have a high risk of developing cardiovascular disease (CVD) or stroke because of sharing risk factors of disease. Therefore, we investigated the risk of CVD or stroke occurrence among HNCA survivors in Korea based on the Health Insurance Review and Assessment (HIRA) Service claims database. Methods We retrieved claims data of patients who were diagnosed with HNCA in 2014‐2015 using ICD‐10 code and followed up data until 2018. Patients with newly diagnosed with CVD or stroke after HNCA diagnosis during the follow‐up period were detected. We analyzed the characteristics of patients with HNCA who were subsequently diagnosed with CVD or stroke. In addition, the risk factors of CVD or stroke occurrence were investigated using Cox proportional hazard regression analysis. Results Among the 8288 patients with HNCA, 477 and 404 patients were diagnosed with new‐onset CVD and stroke, respectively. Patients with hypertension, diabetes mellitus (DM), and hyperlipidemia had a 3.25‐fold higher risk of CVD comparing to patients without any underlying disease (95% confidence index [CI], 2.38‐4.45) Patients with three underlying diseases had a 2.92‐fold higher risk of stroke compared to patients without any underlying disease (95% CI 2.03‐4.21). Conclusions HNCA survivors with hypertension, DM, and hyperlipidemia should be cautious of the risks of CVD and stroke.

Background/Aims Patients with pancreatic cancer (PC) generally have poor clinical outcomes. Early determination of their prognosis is crucial for developing a therapeutic strategy. Recently, various inflammatory markers have been validated as prognostic indicators for many cancers, including PC. However, few studies have evaluated these markers together. Thus, the purpose of this study was to comprehensively evaluate the value of inflammatory markers as prognostic indicators in patients with advanced PC treated with gemcitabine-based chemotherapy as the first line regimen. Methods This was a single-center retrospective study evaluating 302 patients with advanced PC who began first line treatment between November 2004 and August 2016. These patients were monitored until June 2017. Survival rates were assessed with univariate and multivariate analyses. Continuous variables were separated using the normal range or ideal cut-off levels determined by receiver operating curve analyses. Results Among inflammatory markers evaluated, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and C-reactive protein (CRP) to albumin ratio (CRP-albumin ratio) were independent predictors of overall survival (hazard ratio, 1.712, 1.345, and 1.454, respectively). Difference in survival rates was significant (p < 0.001) among three groups divided by the number of marker-related risks. Conclusions Baseline inflammatory markers including NLR, PLR, and CRP-albumin ratio are useful in predicting survival rates in patients with PC. Combining these three markers is proven to be valuable.

BackgroundComplex antithrombotic regimens are recommended for patients with atrial fibrillation (AF) undergoing drug-eluting stent (DES) implantation but carry high bleeding risk.HypothesisWe aimed to evaluate whether left atrial appendage occlusion (LAAO) with dual antiplatelet therapy (DAPT) improve clinical outcomes when compared with multiple antithrombotic therapy (MAT) in patients with AF undergoing DES implantation.MethodsAmong 475 AF patients who underwent DES, 41 patients treated by LAAO with DAPT and 434 patients on MAT were compared. MAT was defined as any combination of warfarin-based antithrombotic therapy. Among the MAT group, 34.8% were on triple antithrombotic therapy. The primary endpoint was a net adverse clinical event (NACE), a composite of cerebrovascular accident (CVA) and major bleeding. Secondary endpoints were CVA, major bleeding, major adverse cardiac and cerebral event (MACCE), MI, cardiovascular death, and all-cause death. Additional analysis between the new oral anticoagulant (NOAC)-based antithrombotic therapy group (n = 45) and the LAAO group was performed for the same endpoints. To adjust the confounding factors, inverse probability of treatment weighting (IPTW) was applied during the endpoint analysis.ResultsThe LAAO group showed higher incidences of diabetes mellitus, prior CVA, higher CHA2DS2-VASc score (4.56±1.55 vs. 2.96±1.60; PConclusionsAmong patients with AF who underwent DES implantation, the LAAO group had better net clinical outcomes for preventing CVA and major bleeding than the MAT group. Further large-scale trials including comparisons with NOACs are warranted.

Background and aimsThe prognosis of stented lesions differs according to in-stent neointimal characteristics on optical coherence tomography (OCT). In particular, patients who show in-stent heterogeneous neointima are associated with a higher incidence of target lesion revascularization (TLR) compared with those who show in-stent non-heterogeneous neointima. However, the relationship between in-stent neointimal characteristics and native coronary atherosclerosis progression has not been clearly elucidated. The study aimed to investigate the relationship between in-stent neointimal characteristics and progression of native atherosclerosis.MethodsThe neointimal characteristics of 377 patients with 377 drug-eluting stents (DESs) were quantitatively and qualitatively assessed using OCT. The OCT-based neointima was categorized as homogeneous (n = 207), heterogeneous (n = 93), and layered (n = 77). The relationship of non-target lesion revascularization (non-TLR) with neointimal characteristics was evaluated after OCT examination of the stents.ResultsAfter a median follow-up duration of 40.0 months, patients with heterogeneous neointima showed significantly higher non-TLR rates than those with homogeneous neointima and tended to have higher non-TLR rates than those with layered neointima (heterogeneous vs. homogeneous:14.0% vs. 8.7%, p = 0.046; heterogeneous vs. layered neointima:14.0% vs. 7.8%, p = 0.152). Multivariate analysis showed that the independent determinants for non-TLR were heterogeneous neointima (HR: 2.237, 95% CI: 1.023-4.890, p = 0.044) and chronic kidney disease (hazard ratio [HR]: 8.730, 95% CI: 2.175-35.036, p = 0.002).ConclusionsThe heterogeneous neointima in DES-treated lesions was associated with a higher incidence of non-TLR and target lesion failure. This finding suggests that the neointimal pattern may reflect the progression of the native lesion.

Background Chrysanthemum boreale Makino (Anthemideae, Asteraceae) is a plant of economic, ornamental and medicinal importance. We characterized and compared the chloroplast genomes of three C. boreale strains. These were collected from different geographic regions of Korea and varied in floral morphology. Methods The chloroplast genomes were obtained by next-generation sequencing techniques, assembled de novo, annotated, and compared with one another. Phylogenetic analysis placed them within the Anthemideae tribe. Results The sizes of the complete chloroplast genomes of the C. boreale strains were 151,012 bp (strain 121002), 151,098 bp (strain IT232531) and 151,010 bp (strain IT301358). Each genome contained 80 unique protein-coding genes, 4 rRNA genes and 29 tRNA genes. Comparative analyses revealed a high degree of conservation in the overall sequence, gene content, gene order and GC content among the strains. We identified 298 single nucleotide polymorphisms (SNPs) and 106 insertions/deletions (indels) in the chloroplast genomes. These variations were more abundant in non-coding regions than in coding regions. Long dispersed repeats and simple sequence repeats were present in both coding and noncoding regions, with greater frequency in the latter. Regardless of their location, these repeats can be used for molecular marker development. Phylogenetic analysis revealed the evolutionary relationship of the species in the Anthemideae tribe. The three complete chloroplast genomes will be valuable genetic resources for studying the population genetics and evolutionary relationships of Asteraceae species.

BackgroundBeta-blockers are often not the preferred treatment for patients with vasospastic angina. However, nebivolol, beta-blocker with nitric oxide-releasing effect, could theoretically improve coronary vasospasm. We compared nebivolol versus diltiazem in improving coronary vasospasm and quality of life in patients with hypertensive vasospastic angina during a 12-week follow-up.MethodsFifty-one hypertensive patients with documented coronary vasospasm were randomly allocated into 3 treatment groups: (1) Nebivolol Group (5mg for 2 weeks/10mg for 10 weeks); (2) Diltiazem Group (90mg for 2 weeks/180mg for 10 weeks); (3) Low-dose Combination Group (2.5mg + 45mg for 2 weeks/5mg + 90mg for 10 weeks). The primary endpoint was to compare the percent changes in coronary vasospasm at 12 weeks from baseline among the 3 groups. The secondary endpoints included changes in quality of life based on the Seattle Angina Questionnaire and changes in blood pressure at 12 weeks from baseline.ResultsSignificant improvements in coronary vasospasm were found in all groups; however, the improvement in percent changes in coronary artery spasm was greatest in the Diltiazem Group (50.4±8.8% vs. 67.8±12.8% vs. 46.8±12.3%, Nebivolol Group vs. Diltiazem Group p = 0.008; Nebivolol Group vs. Low-dose Combination Group p = 0.999; Diltiazem Group vs. Low-dose Combination Group p = 0.017). The overall Seattle Angina Questionnaire scores were significantly elevated at 12 weeks compared to the baseline in entire study population. There were no significant differences between the three groups in the overall Seattle Angina Questionnaire score changes and blood pressure changes.ConclusionsBoth nebivolol and diltiazem showed significant coronary vasospasm reduction effect, but the effect was greater for diltiazem.

Senna tora is an annual herb with rich source of anthraquinones that have tremendous pharmacological properties. However, there is little mention of genetic information for this species, especially regarding the biosynthetic pathways of anthraquinones. To understand the key genes and regulatory mechanism of anthraquinone biosynthesis pathways, we performed spatial and temporal transcriptome sequencing of S. tora using short RNA sequencing (RNA-Seq) and long-read isoform sequencing (Iso-Seq) technologies, and generated two unigene sets composed of 118,635 and 39,364, respectively. A comprehensive functional annotation and classification with multiple public databases identified array of genes involved in major secondary metabolite biosynthesis pathways and important transcription factor (TF) families (MYB, MYB-related, AP2/ERF, C2C2-YABBY, and bHLH). Differential expression analysis indicated that the expression level of genes involved in anthraquinone biosynthetic pathway regulates differently depending on the degree of tissues and seeds development. Furthermore, we identified that the amount of anthraquinone compounds were greater in late seeds than early ones. In conclusion, these results provide a rich resource for understanding the anthraquinone metabolism in S. tora.

AimAlthough the atheroprotective effects of statins and angiotensin II receptor blockers (ARBs) are well-established, little is known about their additive effects, especially during the early period of atherosclerosis. The aim of this study was to investigate whether combination of a statin and an ARB exerts synergistic anti-atherosclerotic effects, and to elucidate the mechanisms of combined effects.MethodsAtherosclerotic plaques were developed in arteries of 23 rabbits using a high-cholesterol diet (HCD) and intra-arterial balloon inflation. Rabbits received one of five different treatment strategies for 4 weeks: positive control [n = 5, HCD]; negative control [n = 3, regular chow diet]; statin [n = 5, HCD and rosuvastatin 10 mg]; ARB [n = 5, HCD and olmesartan 20 mg]; and combination [n = 5, HCD and statin+ARB].ResultsHistological analysis demonstrated that development of atherosclerotic plaques was inhibited more in combination group than in statin group (P = 0.001). Although macrophage infiltration identified by RAM11 staining was not significantly different between combination and individual treatment groups (31.76±4.84% [combination] vs. 38.11±6.53% [statin; P = 0.35] or 35.14±2.87% [ARB; P = 0.62]), the relative proportion of pro-inflammatory M1-macrophages was significantly lower in combination group than in ARB group (3.20±0.47% vs. 5.20±0.78%, P = 0.02). Furthermore, M2-macrophage polarization was higher in combination group than in statin group (17.70±3.04% vs. 7.86±0.68%, P = 0.001).ConclusionCombination treatment with a statin and an ARB produced synergistic protective effects for atherosclerosis initiation and progression, which may be attributed to modulation of macrophage characteristics in the early period of atherosclerosis.

Atherosclerosis is a well-known cause of cardiovascular disease and is associated with a variety of inflammatory reactions. However, an adequate large-animal model of advanced plaques to investigate the pathophysiology of atherosclerosis is lacking. Therefore, we developed and assessed a swine model of advanced atherosclerotic plaques with macrophage polarization.Mini-pigs were fed a 2% high-cholesterol diet for 7 weeks followed by withdrawal periods of 4 weeks. Endothelial denudation was performed using a balloon catheter on 32 coronary and femoral arteries of 8 mini-pigs. Inflammatory proteins (high-mobility group box 1 [HMGB1] or tumor necrosis factor alpha (TNF-α) were injected via a micro-infusion catheter into the vessel wall. All lesions were assessed with angiography and optical coherence tomography and all tissues were harvested for histological evaluation.Intima/plaque area was significantly higher in the HMGB1- and TNF-α-injected groups compared to the saline-injected group (p = 0.002). CD68 antibody detection and polarization of M1 macrophages significantly increased in the inflammatory protein-injected groups (p

BACKGROUND:We evaluated optimal duration of dual antiplatelet therapy (DAPT) after second-generation drug-eluting stent (DES) implantation in acute coronary syndrome (ACS). MATERIAL AND METHODS:From pooled analysis of three randomized clinical trials (EXCELLENT, IVUS-XPL, RESET), a total of 2,216 patient with ACS undergoing second-generation DES implantation were selected. Each study randomized patients to a short-duration DAPT arm (n = 1119; ≤6 months) or a standard-duration DAPT arm (n = 1097; ≥12 months). Two-thirds of patients were male, and their mean age was 63 years. Mean DAPT durations were 164 ±76 and 359 ±68 days, respectively. The primary endpoint was composite of cardiac death, myocardial infarction, stent thrombosis, stroke or major bleeding during the first 12 months after implantation, analyzed according to the intention-to-treat population. RESULTS:Demographic characteristics were balanced between groups. Mean DAPT duration was 164 and 359 days, respectively. Primary endpoint occurred in 22 patients with short-DAPT and 21 patients with standard-DAPT (2.0% versus 1.9%; hazard ratio [HR] 1.03; 95% confidence interval [CI] 0.56-1.86; p = 0.94). Landmark analysis after six-months, no significant difference in primary endpoint between short and standard duration DAPT (1.0% versus 0.8%; HR 1.22; 95% CI 0.51-2.95; p = 0.66). CONCLUSIONS:Short-duration DAPT (≤6 months) demonstrated a similar incidence of net adverse cardiovascular and clinical events at 12 months after second-generation DES in ACS compared with standard duration DAPT (≥12 months). CLINICAL TRIAL REGISTRATION:EXCELLENT (ClinicalTrials.gov, NCT00698607), RESET (ClinicalTrials.gov, NCT01145079), IVUS-XPL (ClinicalTrials.gov, NCT01308281).

OBJECTIVE:Data concerning the effect of current smoking on solely new-generation drug-eluting stents (DES) are limited. We investigated the impact of current smoking on 2-year clinical outcomes between durable-polymer (DP)-coated DES (zotarolimus-eluting [ZES] and everolimus eluting [EES]) and biodegradable-polymer (BP)-coated biolimus-eluting stent (BES) in acute myocardial infarction (AMI) patients after successful percutaneous coronary intervention (PCI). METHODS:Finally, a total of 8357 AMI patients with current smoking underwent successful PCI with new-generation DES (ZES, EES, and BES) were enrolled and divided into three groups as ZES (n = 3199), EES (n = 3987), and BES group (n = 1171). The primary endpoint was the occurrence of major adverse cardiac events (MACE) defined as all-cause death (cardiac death [CD] or non-cardiac death), recurrent AMI (re-MI), any revascularization (target lesion revascularization [TLR], target vessel revascularization [TVR], and non-TVR). The secondary endpoint was the incidence of definite or probable stent thrombosis (ST). RESULTS:The 2-year adjusted hazard ratio (HR) of MACE for ZES vs. EES (1.055; 95% confidence interval [CI], 0.843-1.321; p = 0.638), ZES vs. BES (HR, 0.885; 95% CI, 0.626-1.251; p = 0.488), EES vs. BES (HR, 0.889; 95% CI, 0.633-1.250; p = 0.499), and ZES/EES vs. BES (HR, 0.891; 95% CI, 0.648-1.126; p = 0.480) were similar. The occurrence of ST after adjustment were also comparable. In addition, the 2-year adjusted HR for all-cause death, CD, re-MI, TLR, TVR, and non-TVR were not different. CONCLUSIONS:In this study, DP-DES and BP-DES showed comparable safety and efficacy during 2-year follow-up periods. Therefore, DP-DES or BP-DES are equally acceptable in AMI patients with current smoking undergoing PCI.

Fibrates are used in patients with dyslipidemia and high cardiovascular risk. However, information regarding drug response to fibrate has been highly limited. We investigated treatment results and factors associated with triglyceride reduction after fenofibrate therapy using large-scale real-world data. Patients with one or more cardiovascular risk factors, at low-density lipoprotein-cholesterol goal but with triglyceride level ≥150 mg/dL, and undergoing treatment with fenofibrate 135-160 mg for the first time were included in this retrospective observational study. The outcome variable was the percentage changes of TG levels. The achievement rate of triglyceride