Peripheral arterial disease is associated with coronary artery spasm as assessed by an intracoronary acetylcholine provocation test

Chen, Kang-Yin,Rha, Seung-Woon,Li, Yong-Jian,Poddar, Kanhaiya L,Jin, Zhe,Minami, Yoshiyasu,Wang, Lin,Li, Guang-Ping,Saito, Shigeru,Park, Jae-Hyoung,Na, Jin-Oh,Choi, Cheol Ung,Lim, Hong-Euy,Kim, Jin-Wo Blackwell Publishing Ltd 2009 Clinical and Experimental Pharmacology & Physiolog Vol.36 No.11

<P>Summary</P><P>1. Both peripheral arterial disease (PAD) and coronary artery spasm (CAS) are associated with endothelial dysfunction. Thus, a higher incidence of CAS may be expected in patients with PAD. In the present study, we evaluated the incidence and characteristics of CAS in patients with PAD.</P><P>2. A total of 78 patients with PAD and 241 age- and gender-matched patients without PAD who had chest pain with normal coronary appearance on coronary angiograms underwent intracoronary acetylcholine (ACh) provocation test. Acetylcholine was injected into the left coronary artery in incremental doses of 20, 50 and 100 &mgr;g/min. Significant CAS was defined as a transient > 70% luminal narrowing with concurrent chest pain and/or ST segment changes.</P><P>3. Patients with PAD had a significantly higher incidence of ACh-induced significant CAS than those without PAD (60.3 vs 34.0%, respectively <I>P</I> < 0.001), as well as chest pain and ST segment changes during the ACh provocation test. Patients with PAD were more sensitive to lower doses of ACh and had a higher incidence of multivessel spasm than those without PAD. Multivariable logistic analysis showed that age, current smoking, PAD and myocardial bridge were independent predictors of ACh-induced significant CAS. Moreover, of these factors, PAD was the strongest independent predictor (odds ratio 4.25; confidence interval 1.33–13.54; <I>P</I> = 0.014).</P><P>4. In patients with chest pain, the presence of arterial disease at another site should still push the clinician towards treating the chest pain as angina, even if the coronary anatomy is normal on a coronary angiogram.</P>

Triple versus dual antiplatelet therapy in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Chen, Kang-Yin,Rha, Seung-Woon,Li, Yong-Jian,Poddar, Kanhaiya L,Jin, Zhe,Minami, Yoshiyasu,Wang, Lin,Kim, Eung Ju,Park, Chang Gyu,Seo, Hong Seog,Oh, Dong Joo,Jeong, Myung Ho,Ahn, Young Keun,Hong, Taek American Heart Association, etc.] 2009 CIRCULATION - Vol.119 No.25

<P>BACKGROUND: Whether triple antiplatelet therapy is superior or similar to dual antiplatelet therapy in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention in the era of drug-eluting stents remains unclear. METHODS AND RESULTS: A total of 4203 ST-segment elevation myocardial infarction patients who underwent primary percutaneous coronary intervention with drug-eluting stents were analyzed retrospectively in the Korean Acute Myocardial Infarction Registry (KAMIR). They received either dual (aspirin plus clopidogrel; dual group; n=2569) or triple (aspirin plus clopidogrel plus cilostazol; triple group; n=1634) antiplatelet therapy. The triple group received additional cilostazol at least for 1 month. Various major adverse cardiac events at 8 months were compared between these 2 groups. Compared with the dual group, the triple group had a similar incidence of major bleeding events but a significantly lower incidence of in-hospital mortality. Clinical outcomes at 8 months showed that the triple group had significantly lower incidences of cardiac death (adjusted odds ratio, 0.52; 95% confidence interval, 0.32 to 0.84; P=0.007), total death (adjusted odds ratio, 0.60; 95% confidence interval, 0.41 to 0.89; P=0.010), and total major adverse cardiac events (adjusted odds ratio, 0.74; 95% confidence interval, 0.58 to 0.95; P=0.019) than the dual group. Subgroup analysis showed that older (>65 years old), female, and diabetic patients got more benefits from triple antiplatelet therapy than their counterparts who received dual antiplatelet therapy. CONCLUSIONS: Triple antiplatelet therapy seems to be superior to dual antiplatelet therapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with drug-eluting stents. These results may provide the rationale for the use of triple antiplatelet therapy in these patients.</P>

S100A4 Gene is Crucial for Methionine-Choline-Deficient Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice

Yin-Hua Zhang,De-Ping Ding,De-Qiang Ma,Juan Li,Lin-Li Chen,Kang-Jian Ao,You-You Tian 연세대학교의과대학 2018 Yonsei medical journal Vol.59 No.9

Purpose: To explore the influence of S100 calcium binding protein A4 (S100A4) knockout (KO) on methionine-choline-deficient(MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) in mice. Materials and Methods: S100A4 KO mice (n=20) and their wild-type (WT) counterparts (n=20) were randomly divided into KO/MCD, Ko/methionine-choline-sufficient (MCS), WT/MCD, and WT/MCS groups. After 8 weeks of feeding, blood lipid and liverfunction-related indexes were measured. HE, Oil Red O, and Masson stainings were used to observe the changes of liver histopathology. Additionally, expressions of S100A4 and proinflammatory and profibrogenic cytokines were detected by qRT-PCR andWestern blot, while hepatocyte apoptosis was revealed by TUNEL staining. Results: Serum levels of aminotransferase, aspartate aminotransferase, triglyceride, and total cholesterol in mice were increasedafter 8-week MCD feeding, and hepatocytes performed varying balloon-like changes with increased inflammatory cell infiltrationand collagen fibers; however, these effects were improved in mice of KO/MCD group. Meanwhile, total NAFLD activity scoresand fibrosis were lower compared to WT+MCD group. Compared to WT/MCS group, S100A4 expression in liver tissue of WT/MCD group was enhanced. The expression of proinflammatory (TNF-α, IL-1β, IL-6) and profibrogenic cytokines (TGF-β1, COL1A1,α-SMA) in MCD-induced NAFLD mice were increased, as well as apoptotic index (AI). For MCD group, the expressions ofproinflammatory and profibrogenic cytokines and AI in KO mice were lower than those of WT mice. Conclusion: S100A4 was detected to be upregulated in NAFLD, while S100A4 KO alleviated liver fibrosis and inflammation, inaddition to inhibiting hepatocyte apoptosis.

Impact of Heterogeneous Overlapping Drug-Eluting Stents on the Arterial Responses of Rabbit Iliac Arteries: A Comparison With Overlapping Bare Metal Stents

나승운,Kang-Yin Chen,오동주,Yong-Jian Li,Zhe Jin,Kanhaiya Lal Poddar,Sureshkumar Ramasamy,Yoshiyasu Minami,Amro Elnagar,최병걸,Sang Pyo Hong,Byoung Won Cheon,Sang Ki Moon,Sung Il Im,Sun Won Kim,나진오,홍영준,임홍의,김진원 대한심장학회 2012 Korean Circulation Journal Vol.42 No.6

Background and Objectives: Although the use of heterogeneous overlapping drug-eluting stents (DES) is not uncommon in clinical practice, whether the implantation sequences of heterogeneous DES will influence the endothelialization or arterial responses differently remains unclear. Materials and Methods: Twenty-one rabbits were randomized to receive overlapping stents in the iliac artery for 3 months {distal siroli-mus-eluting stent (SES, Cypher TM )+proximal paclitaxel-eluting stent (PES, Taxus TM ) (C+T, n=7), distal Taxus+proximal Cypher (T+C, n=7) and bare metal stent (BMS)+BMS (B+B, n=7)}. Endothelial function was evaluated by the acetylcholine provocation test during follow-up an-giography. Histopathological changes in proximal, overlapped, and distal stented segments were evaluated. Results: Although the overall angiographic outcomes were comparable, late loss (mm) in the distal stented segment was higher in the B+B (0.39±0.07) and C+T (0.40±0.20) than that in the T+C (0.06±0.02) group (p<0.001). The incidence of acetylcholine-induced spasm was higher in the DES groups compared with BMS, regardless of the implantation sequences (85.7% in C+T vs. 14.3% in B+B vs. 71.4% in T+C,p=0.017). Notably, only the distal Cypher implantation group (C+T) had three cases of stent fracture. A histopathological analysis showed that despite similar arterial injury scores, Taxus and Cypher stents had higher inflammatory reactions at the overlapped and distal segments compared with those of BMS. Conclusion: Despite similar arterial injury, higher inflammatory reactions were observed in overlapping DES segments regardless of the im -plantation sequence compared with that of BMS. Moreover, DES was associated with impaired endothelial function on the adjacent non-stented segments.

Genomic and Transcriptomic Characterization Revealed the High Sensitivity of Targeted Therapy and Immunotherapy in a Subset of Endometrial Stromal Sarcoma

Nan Kang,Yinli Zhang,Shichao Guo,Ran Chen,Fangzhou Kong,Shuchun Wang,Mingming Yuan,Rongrong Chen,Danhua Shen,Jianliu Wang 대한암학회 2023 Cancer Research and Treatment Vol.55 No.3

Purpose The unique chromosomal rearrangements of endometrial stromal sarcoma (ESS) make it possible to distinguish high-grade ESS (HGESS) and low-grade ESS (LGESS) from the molecular perspective. Analysis of ESS at the genomic and transcriptomic levels can help us achieve accurate diagnosis of ESS and provide potential therapy options for ESS patients.Materials and Methods A total of 36 ESS patients who conducted DNA- and/or RNA-based next-generation sequencing were retrospectively enrolled in this study. The molecular characteristics of ESS at genomic and transcriptomic levels, including mutational spectrum, fusion profiles, gene expression and pathway enrichment analysis and features about immune microenvironment were comprehensively explored.Results <i>TP53</i> and <i>DNMT3A</i> mutations were the most frequent mutations. The classical fusions frequently found in <i>HGESS</i> (<i>ZC3H7B-BCOR</i> and <i>NUTM2B-YWHAE</i>) and LGESS (<i>JAZF1-SUZ12</i>) were detected in our cohort. <i>CCND1</i> was significantly up-regulated in HGESS, while the expression of <i>GPER1</i> and <i>PGR</i> encoding estrogen receptor (ER) and progesterone receptor (PR) did not differ significantly between HGESS and LGESS. Actionable mutations enriched in homologous recombination repair, cell cycle, and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways were detected in 60% of HGESS patients. Genes with up-regulated expression in HGESS were significantly enriched in five immune-related pathways. Most HGESS patients (85.7%) had positive predictors of immunotherapy efficacy. Moreover, immune microenvironment analysis showed that HGESS had relatively high immune infiltration. The degree of immune infiltration in HGESS patients with <i>ZC3H7B-BCOR</i> fusion was relatively higher than that of those with <i>NUTM2B-YWHAE</i> fusion.Conclusion This study investigated the molecular characteristics of ESS patients at the genomic and transcriptomic levels and revealed the potentially high sensitivity of targeted therapy and immunotherapy in a subset of HGESS with specific molecular features, providing a basis for guiding decision-making of treatment and the design of future clinical trials on precision therapy.

Analysis of Active Ion‑Leaching Behavior and the Reaction Mechanism During Alkali Activation of Low‑Calcium Fly Ash

Bo Yin,Tianhe Kang,Jianting Kang,Yuejuan Chen 한국콘크리트학회 2018 International Journal of Concrete Structures and M Vol.12 No.5

The dissolution and release of active ions, such as Si<SUP>4+</SUP>, Al<SUP>3+</SUP> and Ca<SUP>2+</SUP>, from fly ash directly affect the rate and extent of reaction product formation, which in turn affect the physical and mechanical properties of fly ash filling materials. In this study, low-calcium fly ash was soaked and activated in NaOH solutions with different concentrations (approximating the optimum dose range) for different lengths of time. The amounts of active ions leached and the changes in the mineral composition, chemical functional groups and surface morphology were tested and analyzed via ICP-OES, XRD, FTIR and SEM/EDS techniques. Based on these analyses, the reaction mechanism of alkali activation of low-calcium fly ash was further investigated. The results showed that the NaOH activation effect can significantly increase the amount of active ions leached from low-calcium fly ash. Notably, the amount of Si<SUP>4+</SUP> and Al<SUP>3+</SUP> leached clearly increased with increases in both NaOH concentration and soaking time. The plausible reaction mechanism is discussed in detail, which is that the alkali activator principally affected the surface of the vitreous particles of lowcalcium fly ash and induced differing surface modifications in the dissolution stage, depolymerization stage, polycondensation and polymer gel stage and diffusion stage. It was observed that the progress of the reaction is controlled by dissolution in the early stages, whereas activation is governed by diffusion when the surfaces of the fly ash particles are covered by precipitates.

A review of rotorcraft Unmanned Aerial Vehicle (UAV) developments and applications in civil engineering

Liu, Peter,Chen, Albert Y.,Huang, Yin-Nan,Han, Jen-Yu,Lai, Jihn-Sung,Kang, Shih-Chung,Wu, Tzong-Hann,Wen, Ming-Chang,Tsai, Meng-Han Techno-Press 2014 Smart Structures and Systems, An International Jou Vol.13 No.6

Civil engineers always face the challenge of uncertainty in planning, building, and maintaining infrastructure. These works rely heavily on a variety of surveying and monitoring techniques. Unmanned aerial vehicles (UAVs) are an effective approach to obtain information from an additional view, and potentially bring significant benefits to civil engineering. This paper gives an overview of the state of UAV developments and their possible applications in civil engineering. The paper begins with an introduction to UAV hardware, software, and control methodologies. It also reviews the latest developments in technologies related to UAVs, such as control theories, navigation methods, and image processing. Finally, the paper concludes with a summary of the potential applications of UAV to seismic risk assessment, transportation, disaster response, construction management, surveying and mapping, and flood monitoring and assessment.

BRD4 Inhibition Is Synthetic Lethal with PARP Inhibitors through the Induction of Homologous Recombination Deficiency

Sun, Chaoyang,Yin, Jun,Fang, Yong,Chen, Jian,Jeong, Kang Jin,Chen, Xiaohua,Vellano, Christopher P.,Ju, Zhenlin,Zhao, Wei,Zhang, Dong,Lu, Yiling,Meric-Bernstam, Funda,Yap, Timothy A.,Hattersley, Mauree Cell Press 2018 CANCER CELL Vol. No.

<P><B>Summary</B></P> <P>Poly(ADP-ribose) polymerase inhibitors (PARPi) are selectively active in cells with homologous recombination (HR) deficiency (HRD) caused by mutations in <I>BRCA1</I>, <I>BRCA2</I>, and other pathway members. We sought small molecules that induce HRD in HR-competent cells to induce synthetic lethality with PARPi and extend the utility of PARPi. We demonstrated that inhibition of bromodomain containing 4 (BRD4) induced HRD and sensitized cells across multiple tumor lineages to PARPi regardless of <I>BRCA1/2</I>, <I>TP53</I>, <I>RAS</I>, or <I>BRAF</I> mutation status through depletion of the DNA double-stand break resection protein CtIP (C-terminal binding protein interacting protein). Importantly, BRD4 inhibitor (BRD4i) treatment reversed multiple mechanisms of resistance to PARPi. Furthermore, PARPi and BRD4i are synergistic in multiple <I>in vivo</I> models.</P> <P><B>Highlights</B></P> <P> <UL> <LI> BRD4 inhibition decreases homologous recombination competency by decreasing CtIP </LI> <LI> PARP and BRD4 inhibitors demonstrate synergy in multiple cancer lineages </LI> <LI> CtIP rescues DNA end resection and HR defect caused by BRD4 inhibition </LI> <LI> BRD4 inhibition resensitizes cells with acquired PARPi resistance to PARPi </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>

A review of rotorcraft Unmanned Aerial Vehicle (UAV) developments and applications in civil engineering

Peter Liu,Albert Y. Chen,Yin-Nan Huang,Jen-Yu Han,Jihn-Sung Lai,Tzong-Hann Wu,Ming-Chang Wen,Meng-Han Tsai,Shih-Chung Kang 국제구조공학회 2014 Smart Structures and Systems, An International Jou Vol.13 No.6

Civil engineers always face the challenge of uncertainty in planning, building, and maintaininginfrastructure. These works rely heavily on a variety of surveying and monitoring techniques. Unmannedaerial vehicles (UAVs) are an effective approach to obtain information from an additional view, andpotentially bring significant benefits to civil engineering. This paper gives an overview of the state of UAVdevelopments and their possible applications in civil engineering. The paper begins with an introduction toUAV hardware, software, and control methodologies. It also reviews the latest developments in technologiesrelated to UAVs, such as control theories, navigation methods, and image processing. Finally, the paperconcludes with a summary of the potential applications of UAV to seismic risk assessment, transportation,disaster response, construction management, surveying and mapping, and flood monitoring and assessment.

Rational combination therapy with PARP and MEK inhibitors capitalizes on therapeutic liabilities in <i>RAS</i> mutant cancers

Sun, Chaoyang,Fang, Yong,Yin, Jun,Chen, Jian,Ju, Zhenlin,Zhang, Dong,Chen, Xiaohua,Vellano, Christopher P.,Jeong, Kang Jin,Ng, Patrick Kwok-Shing,Eterovic, Agda Karina B.,Bhola, Neil H.,Lu, Yiling,Wes American Association for the Advancement of Scienc 2017 Science translational medicine Vol.9 No.392

<P>Mutant <I>RAS</I> has remained recalcitrant to targeted therapy efforts. We demonstrate that combined treatment with poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors and mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitors evokes unanticipated, synergistic cytotoxic effects in vitro and in vivo in multiple <I>RAS</I> mutant tumor models across tumor lineages where <I>RAS</I> mutations are prevalent. The effects of PARP and MEK inhibitor combinations are independent of <I>BRCA1/2</I> and <I>p53</I> mutation status, suggesting that the synergistic activity is likely to be generalizable. Synergistic activity of PARP and MEK inhibitor combinations in <I>RAS</I> mutant tumors is associated with (i) induction of BIM-mediated apoptosis, (ii) decrease in expression of components of the homologous recombination DNA repair pathway, (iii) decrease in homologous recombination DNA damage repair capacity, (iv) decrease in DNA damage checkpoint activity, (v) increase in PARP inhibitor–induced DNA damage, (vi) decrease in vascularity that could increase PARP inhibitor efficacy by inducing hypoxia, and (vii) elevated PARP1 protein, which increases trapping activity of PARP inhibitors. Mechanistically, enforced expression of FOXO3a, which is a target of the RAS/MAPK pathway, was sufficient to recapitulate the functional consequences of MEK inhibitors including synergy with PARP inhibitors. Thus, the ability of mutant <I>RAS</I> to suppress FOXO3a and its reversal by MEK inhibitors accounts, at least in part, for the synergy of PARP and MEK inhibitors in <I>RAS</I> mutant tumors. The rational combination of PARP and MEK inhibitors warrants clinical investigation in patients with <I>RAS</I> mutant tumors where there are few effective therapeutic options.</P>