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author:("Wu, liqui")
1.  Restitution characteristics of His bundle and working myocardium in isolated rabbit hearts 
PLoS ONE  2017;12(10):e0186880.
The Purkinje system (PS) and the His bundle have been recently implicated as an important driver of the rapid activation rate after 1–2 minutes of ventricular fibrillation (VF). It is unknown whether activations during VF propagate through the His-Purkinje system to other portions of the the working myocardium (WM). Little is known about restitution characteristic differences between the His bundle and working myocardium at short cycle lengths. In this study, rabbit hearts (n = 9) were isolated, Langendorff-perfused, and electromechanically uncoupled with blebbistatin (10 μM). Pacing pulses were delivered directly to the His bundle. By using standard glass microelectrodes, action potentials duration (APD) from the His bundle and WM were obtained simultaneously over a wide range of stimulation cycle lengths (CL). The global F-test indicated that the two restitution curves of the His bundle and the WM are statistically significantly different (P<0.05). Also, the APD of the His bundle was significantly shorter than that of WM throughout the whole pacing course (P<0.001). The CL at which alternans developed in the His bundle vs. the WM were shorter for the His bundle (134.2±13.1ms vs. 148.3±13.3ms, P<0.01) and 2:1 block developed at a shorter CL in the His bundle than in WM (130.0±10.0 vs. 145.6±14.2ms, P<0.01). The His bundle APD was significantly shorter than that of WM under both slow and rapid pacing rates, which suggest that there may be an excitable gap during VF and that the His bundle may conduct wavefronts from one bundle branch to the other at short cycle lengths and during VF.
doi:10.1371/journal.pone.0186880
PMCID: PMC5658095  PMID: 29073179
2.  Up-regulation of CIT promotes the growth of colon cancer cells 
Oncotarget  2017;8(42):71954-71964.
Colon cancer is one of the major causes of cancer mortality worldwide. However, the underlying mechanism and therapeutic targets of colon cancer have not yet been fully elucidated. In the present study, we demonstrate that citron rho-interacting, serine/threonine kinase 21 (CIT) promotes the growth of human colon cancer cells. CIT is overexpressed in human colon cancer tissues and cell lines. High expression of CIT predicts poor survival for patients with colon cancer. In colon cancer cells, CIT knockdown represses cellular proliferation and colony formation. Our in vivo xenograft experiments showed that CIT knockdown reduces the growth rate of colon cancer cells and the final tumor weight. We found that CIT knockdown induces cell cycle arrest and apoptosis in colon cancer cells. Further microarray and bioinformatics analyses indicated that CIT regulates the p53 signaling pathway, which may account for the effects of CIT on colon cancer cells. Taken together, our findings provide evidence that CIT may promote the development of colon cancer, at least in part, through the p53 signaling pathway. Therefore, CIT may be a potential therapeutic target for colon cancer treatment.
doi:10.18632/oncotarget.18615
PMCID: PMC5641103
CIT; colon cancer; cell growth; apoptosis; p53
3.  World Congress Integrative Medicine & Health 2017: Part one 
Brinkhaus, Benno | Falkenberg, Torkel | Haramati, Aviad | Willich, Stefan N. | Briggs, Josephine P. | Willcox, Merlin | Linde, Klaus | Theorell, Töres | Wong, Lisa M. | Dusek, Jeffrey | Wu, Darong | Eisenberg, David | Haramati, Aviad | Berger, Bettina | Kemper, Kathi | Stock-Schröer, Beate | Sützl-Klein, Hedda | Ferreri, Rosaria | Kaplan, Gary | Matthes, Harald | Rotter, Gabriele | Schiff, Elad | Arnon, Zahi | Hahn, Eckhard | Luberto, Christina M. | Martin, David | Schwarz, Silke | Tauschel, Diethard | Flower, Andrew | Gramminger, Harsha | Gupta, Hedwig H. | Gupta, S. N. | Kerckhoff, Annette | Kessler, Christian S. | Michalsen, Andreas | Kessler, Christian S. | Kim, Eun S. | Jang, Eun H. | Kim, Rana | Jan, Sae B. | Mittwede, Martin | Mohme, Wiebke | Ben-Arye, Eran | Bonucci, Massimo | Saad, Bashar | Breitkreuz, Thomas | Rossi, Elio | Kebudi, Rejin | Daher, Michel | Razaq, Samaher | Gafer, Nahla | Nimri, Omar | Hablas, Mohamed | Kienle, Gunver Sophia | Samuels, Noah | Silbermann, Michael | Bandelin, Lena | Lang, Anna-Lena | Wartner, Eva | Holtermann, Christoph | Binstock, Maxwell | Riebau, Robert | Mujkanovic, Edin | Cramer, Holger | Lauche, Romy | Michalsen, Andres | Ward, Lesley | Cramer, Holger | Irnich, Dominik | Stör, Wolfram | Burnstock, Geoffrey | Schaible, Hans-Georg | Ots, Thomas | Langhorst, Jost | Lauche, Romy | Sundberg, Tobias | Falkenberg, Torkel | Amarell, Catherina | Amarell, Catherina | Anheyer, Melanie | Eckert, Marion | Eckert, Marion | Ogal, Mercedes | Eckert, Marion | Amarell, Catherina | Schönauer, Annette | Reisenberger, Birgit | Brand, Bernhard | Anheyer, Dennis | Dobos, Gustav | Kroez, Matthias | Martin, David | Matthes, Harald | Ammendola, Aldo | Mao, Jun J. | Witt, Claudia | Yang, Yufei | Dobos, Gustav | Oritz, Miriam | Horneber, Markus | Voiß, Petra | Reisenberger, Birgit | von Rosenstiel, Alexandra | Eckert, Marion | Ogal, Mercedes | Amarell, Catharina | Anheyer, Melanie | Schad, Friedemann | Schläppi, Marc | Kröz, Matthias | Büssing, Arndt | Bar-Sela, Gil | Matthes, Harald | Schiff, Elad | Ben-Arye, Eran | Arnon, Zahi | Avshalomov, David | Attias, Samuel | Schönauer, Annette | Haramati, Aviad | Witt, Claudia | Brinkhaus, Benno | Cotton, Sian | Jong, Miek | Jong, Mats | Scheffer, Christian | Haramati, Aviad | Tauschel, Diethard | Edelhäuser, Friedrich | AlBedah, Abdullah | Lee, Myeong Soo | Khalil, Mohamed | Ogawa, Keiko | Motoo, Yoshiharu | Arimitsu, Junsuke | Ogawa, Masao | Shimizu, Genki | Stange, Rainer | Kraft, Karin | Kuchta, Kenny | Watanabe, Kenji | Bonin, D | Büssing, Arndt | Gruber, Harald | Koch, Sabine | Gruber, Harald | Pohlmann, Urs | Caldwell, Christine | Krantz, Barbara | Kortum, Ria | Martin, Lily | Wieland, Lisa S. | Kligler, Ben | Gould-Fogerite, Susan | Zhang, Yuqing | Wieland, Lisa S. | Riva, John J. | Lumpkin, Michael | Ratner, Emily | Ping, Liu | Jian, Pei | Hamme, Gesa-Meyer | Mao, Xiaosong | Chouping, Han | Schröder, Sven | Hummelsberger, Josef | Wullinger, Michael | Brodzky, Marc | Zalpour, Christoff | Langley, Julia | Weber, Wendy | Mudd, Lanay M. | Wayne, Peter | Witt, Clauda | Weidenhammer, Wolfgang | Fønnebø, Vinjar | Boon, Heather | Steel, Amie | Bugarcic, Andrea | Rangitakatu, Melisa | Steel, Amie | Adams, Jon | Sibbritt, David | Wardle, Jon | Leach, Matthew | Schloss, Janet | Dieze, Helene | Boon, Heather | Ijaz, Nadine | Willcox, Merlin | Heinrich, Michael | Lewith, George | Flower, Andrew | Graz, Bertrand | Adam, Daniela | Grabenhenrich, Linus | Ortiz, Miriam | Binting, Sylvia | Reinhold, Thomas | Brinkhaus, Benno | Andermo, Susanne | Sundberg, Tobias | Falkenberg, Torkel | Nordberg, Johanna Hök | Arman, Maria | Bhasin, Manoj | Fan, Xueyi | Libermann, Towia | Fricchione, Gregory | Denninger, John | Benson, Herbert | Berger, Bettina | Stange, Rainer | Michalsen, Andreas | Martin, David D. | Boers, Inge | Vlieger, Arine | Jong, Miek | Brinkhaus, Benno | Teut, Michael | Ullmann, Alexander | Ortiz, Miriam | Rotter, Gabriele | Binting, Sylvia | Lotz, Fabian | Roll, Stephanie | Canella, Claudia | Mikolasek, Michael | Rostock, Matthias | Beyer, Jörg | Guckenberger, Matthias | Jenewein, Josef | Linka, Esther | Six, Claudia | Stoll, Sarah | Stupp, Roger | Witt, Claudia M. | Chuang, Elisabeth | Kligler, Ben | McKee, Melissa D. | Cramer, Holger | Lauche, Romy | Klose, Petra | Lange, Silke | Langhorst, Jost | Dobos, Gustav | Chung, Vincent C. H. | Wong, Hoi L. C. | Wu, Xin Y. | Wen, Grace Y. G. | Ho, Robin S. T. | Ching, Jessica Y. L. | Wu, Justin C. Y. | Coakley, Amanda | Flanagan, Jane | Annese, Christine | Empoliti, Joanne | Gao, Zishan | Liu, Xugang | Yu, Shuguang | Yan, Xianzhong | Liang, Fanrong | Hohmann, Christoph D. | Steckhan, Nico | Ostermann, Thomas | Paetow, Arion | Hoff, Evelyn | Michalsen, Andreas | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Jeitler, Michael | Zillgen, Hannah | Högl, Manuel | Steckhan, Nico | Stöckigt, Barbara | Seifert, Georg | Michalsen, Andreas | Kessler, Christian | Khadivzadeh, Talat | Bashtian, Maryam Hassanzadeh | Aval, Shapour Badiee | Esmaily, Habibollah | Kim, Jihye | Kim, Keun H. | Klocke, Carina | Joos, Stefanie | Koshak, Abdulrahman | Wie, Li | Koshak, Emad | Wali, Siraj | Alamoudi, Omer | Demerdash, Abdulrahman | Qutub, Majdy | Pushparaj, Peter | Heinrich, Michael | Kruse, Sigrid | Fischer, Isabell | Tremel, Nadine | Rosenecker, Joseph | Leung, Brenda | Takeda, Wendy | Liang, Ning | Feng, Xue | Liu, Jian-ping | Cao, Hui-juan | Luberto, Christina M. | Shinday, Nina | Philpotts, Lisa | Park, Elyse | Fricchione, Gregory L. | Yeh, Gloria | Munk, Niki | Zakeresfahani, Arash | Foote, Trevor R. | Ralston, Rick | Boulanger, Karen | Özbe, Dominik | Gräßel, Elmar | Luttenberger, Katharina | Pendergrass, Anna | Pach, Daniel | Bellmann-Strobl, Judit | Chang, Yinhui | Pasura, Laura | Liu, Bin | Jäger, Sven F. | Loerch, Ronny | Jin, Li | Brinkhaus, Benno | Ortiz, Miriam | Reinhold, Thomas | Roll, Stephanie | Binting, Sylvia | Icke, Katja | Shi, Xuemin | Paul, Friedemann | Witt, Claudia M. | Rütz, Michaela | Lynen, Andreas | Schömitz, Meike | Vahle, Maik | Salomon, Nir | Lang, Alon | Lahat, Adi | Kopylov, Uri | Ben-Horin, Shomron | Har-Noi, Ofir | Avidan, Benjamin | Elyakim, Rami | Gamus, Dorit | NG, Siew | Chang, Jessica | Wu, Justin | Kaimiklotis, John | Schumann, Dania | Buttó, Ludovica | Langhorst, Jost | Dobos, Gustav | Haller, Dirk | Cramer, Holger | Smith, Caroline | de Lacey, Sheryl | Chapman, Michael | Ratcliffe, Julie | Johnson, Neil | Lyttleton, Jane | Boothroyd, Clare | Fahey, Paul | Tjaden, Bram | van Vliet, Marja | van Wietmarschen, Herman | Jong, Miek | Tröger, Wilfried | Vuolanto, Pia | Aarva, Paulina | Sorsa, Minna | Helin, Kaija | Wenzel, Claudia | Zoderer, Iris | Pammer, Patricia | Simon, Patrick | Tucek, Gerhard | Wode, Kathrin | Henriksson, Roger | Sharp, Lena | Stoltenberg, Anna | Nordberg, Johanna Hök | Xiao-ying, Yang | Wang, Li-qiong | Li, Jin-gen | Liang, Ning | Wang, Ying | Liu, Jian-ping | Balneaves, Lynda | Capler, Rielle | Bocci, Chiara | Guffi, Marta | Paolini, Marina | Meaglia, Ilaria | Porcu, Patrizia | Ivaldi, Giovanni B. | Dragan, Simona | Bucuras, Petru | Pah, Ana M. | Badalica-Petrescu, Marius | Buleu, Florina | Hogea-Stoichescu, Gheorghe | Christodorescu, Ruxandra | Kao, Lan | Cho, Yumin | Klafke, Nadja | Mahler, Cornelia | von Hagens, Cornelia | Uhlmann, Lorenz | Bentner, Martina | Schneeweiss, Andreas | Mueller, Andreas | Szecsenyi, Joachim | Joos, Stefanie | Neri, Isabella | Ortiz, Miriam | Schnabel, Katharina | Teut, Michael | Rotter, Gabriele | Binting, Sylvia | Cree, Margit | Lotz, Fabian | Suhr, Ralf | Brinkhaus, Benno | Rossi, Elio | Baccetti, Sonia | Firenzuoli, Fabio | Monechi, Maria V. | Di Stefano, Mariella | Amunni, Gianni | Wong, Wendy | Chen, Bingzhong | Wu, Justin | Amri, Hakima | Haramati, Aviad | Kotlyanskaya, Lucy | Anderson, Belinda | Evans, Roni | Kligler, Ben | Marantz, Paul | Bradley, Ryan | Booth-LaForce, Cathryn | Zwickey, Heather | Kligler, Benjamin | Brooks, Audrey | Kreitzer, Mary J. | Lebensohn, Patricia | Goldblatt, Elisabeth | Esmel-Esmel, Neus | Jiménez-Herrera, Maria | Ijaz, Nadine | Boon, Heather | Jocham, Alexandra | Stock-Schröer, Beate | Berberat, Pascal O. | Schneider, Antonius | Linde, Klaus | Masetti, Morgana | Murakozy, Henriette | Van Vliet, Marja | Jong, Mats | Jong, Miek | Agdal, Rita | Atarzadeh, Fatemeh | Jaladat, Amir M. | Hoseini, Leila | Amini, Fatemeh | Bai, Chen | Liu, Tiegang | Zheng, Zian | Wan, Yuxiang | Xu, Jingnan | Wang, Xuan | Yu, He | Gu, Xiaohong | Daneshfard, Babak | Nimrouzi, Majid | Tafazoli, Vahid | Alorizi, Seyed M. Emami | Saghebi, Seyed A. | Fattahi, Mohammad R. | Salehi, Alireza | Rezaeizadeh, Hossein | Zarshenas, Mohammad M. | Nimrouzi, Majid | Fox, Kealoha | Hughes, John | Kostanjsek, Nenad | Espinosa, Stéphane | Lewith, George | Fisher, Peter | Latif, Abdul | Lefeber, Donald | Paske, William | Öztürk, Ali Ö. | Öztürk, Gizemnur | Boers, Inge | Tissing, Wim | Naafs, Marianne | Busch, Martine | Jong, Miek | Daneshfard, Babak | Sanaye, Mohammad R. | Dräger, Kilian | Fisher, Peter | Kreitzer, Mary J. | Evans, Roni | Leininger, Brent | Shafto, Kate | Breen, Jenny | Sanaye, Mohammad R. | Daneshfard, Babak | Simões-Wüst, Ana P. | Moltó-Puigmartí, Carolina | van Dongen, Martien | Dagnelie, Pieter | Thijs, Carel | White, Shelley | Wiesener, Solveig | Salamonsen, Anita | Stub, Trine | Fønnebø, Vinjar | Abanades, Sergio | Blanco, Mar | Masllorens, Laia | Sala, Roser | Al-Ahnoumy, Shafekah | Han, Dongwoon | He, Luzhu | Kim, Ha Yun | In Choi, Da | Alræk, Terje | Stub, Trine | Kristoffersen, Agnete | von Sceidt, Christel | Michalsen, Andreas | Bruset, Stig | Musial, Frauke | Anheyer, Dennis | Cramer, Holger | Lauche, Romy | Saha, Felix J. | Dobos, Gustav | Anheyer, Dennis | Haller, Heidemarie | Lauche, Romy | Dobos, Gustav | Cramer, Holger | Azizi, Hoda | Khadem, Nayereh | Hassanzadeh, Malihe | Estiri, Nazanin | Azizi, Hamideh | Tavassoli, Fatemeh | Lotfalizadeh, Marzieh | Zabihi, Reza | Esmaily, Habibollah | Azizi, Hoda | Shabestari, Mahmoud Mohammadzadeh | Paeizi, Reza | Azari, Masoumeh Alvandi | Bahrami-Taghanaki, Hamidreza | Zabihi, Reza | Azizi, Hamideh | Esmaily, Habibollah | Baars, Erik | De Bruin, Anja | Ponstein, Anne | Baccetti, Sonia | Di Stefano, Mariella | Rossi, Elio | Firenzuoli, Fabio | Segantini, Sergio | Monechi, Maria Valeria | Voller, Fabio | Barth, Jürgen | Kern, Alexandra | Lüthi, Sebastian | Witt, Claudia | Barth, Jürgen | Zieger, Anja | Otto, Fabius | Witt, Claudia | Beccia, Ariel | Dunlap, Corina | Courneene, Brendan | Bedregal, Paula | Passi, Alvaro | Rodríguez, Alfredo | Chang, Mayling | Gutiérrez, Soledad | Beissner, Florian | Beissner, Florian | Preibisch, Christine | Schweizer-Arau, Annemarie | Popovici, Roxana | Meissner, Karin | Beljanski, Sylvie | Belland, Laura | Rivera-Reyes, Laura | Hwang, Ula | Berger, Bettina | Sethe, Dominik | Hilgard, Dörte | Heusser, Peter | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Holmes, Michelle | Lewith, George | Yardley, Lucy | Little, Paul | Cooper, Cyrus | Bogani, Patrizia | Maggini, Valentina | Gallo, Eugenia | Miceli, Elisangela | Biffi, Sauro | Mengoni, Alessio | Fani, Renato | Firenzuoli, Fabio | Brands-Guendling, Nadine | Guendling, Peter W. | Bronfort, Gert | Evans, Roni | Haas, Mitch | Leininger, Brent | Schulz, Craig | Bu, Xiangwei | Wang, J. | Fang, T. | Shen, Z. | He, Y. | Zhang, X. | Zhang, Zhengju | Wang, Dali | Meng, Fengxian | Büssing, Arndt | Baumann, Klaus | Frick, Eckhard | Jacobs, Christoph | Büssing, Arndt | Grünther, Ralph-Achim | Lötzke, Désirée | Büssing, Arndt | Jung, Sonny | Lötzke, Désirée | Recchia, Daniela R. | Robens, Sibylle | Ostermann, Thomas | Berger, Bettina | Stankewitz, Josephin | Kröz, Matthias | Jeitler, Mika | Kessler, Christian | Michalsen, Andreas | Cheon, Chunhoo | Jang, Bo H. | Ko, Seong G. | Huang, Ching W. | Sasaki, Yui | Ko, Youme | Cheshire, Anna | Ridge, Damien | Hughes, John | Peters, David | Panagioti, Maria | Simon, Chantal | Lewith, George | Cho, Hyun J. | Han, Dongwoon | Choi, Soo J. | Jung, Young S. | Im, Hyea B | Cooley, Kieran | Tummon-Simmons, Laura | Cotton, Sian | Luberto, Christina M. | Wasson, Rachel | Kraemer, Kristen | Sears, Richard | Hueber, Carly | Derk, Gwendolyn | Lill, JR | An, Ruopeng | Steinberg, Lois | Rodriguez, Lourdes Diaz | la Fuente, Francisca García-de | De la Vega, Miguel | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Cantarero-Villanueva, Irene | Rodriguez, Lourdes Diaz | García-De la Fuente, Francisca | Jiménez-Guerrero, Fanny | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Galiano-Castillo, Noelia | Diaz-Saez, Gualberto | Torres-Jimenez, José I. | Garcia-Gomez, Olga | Hortal-Muñoz, Luis | Diaz-Diez, Camino | Dicen, Demijon | Diezel, Helene | Adams, Jon | Steel, Amie | Wardle, Jon | Diezel, Helene | Steel, Amie | Frawley, Jane | Wardle, Jon | Broom, Alex | Adams, Jon | Dong, Fei | Yu, He | Liu, Tiegang | Ma, Xueyan | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Gu, Xiaohong | Dong, Fei | Yu, He | Wu, Liqun | Liu, Tiegang | Ma, Xueyan | Ma, Jiaju | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Zhen, Jianhua | Gu, Xiaohong | Dubois, Julie | Rodondi, Pierre-Yves | Edelhäuser, Friedrich | Schwartze, Sophia | Trapp, Barbara | Cysarz, Dirk
doi:10.1186/s12906-017-1782-4
PMCID: PMC5498855
4.  Noninvasive Imaging of High Frequency Drivers and Reconstruction of Global Dominant Frequency Maps in Patients with Paroxysmal and Persistent Atrial Fibrillation 
Objective
Highest dominant-frequency (DF) drivers maintaining atrial fibrillation (AF) activities are effective ablation targets for restoring sinus rhythms in patients. This study aims to investigate whether AF drivers with highest activation rate can be noninvasively localized by means of a frequency-based cardiac electrical imaging (CEI) technique, which may aid in the planning of ablation strategy and the investigation of the underlying mechanisms of AF.
Method
A total of 7 out of 13 patients were recorded with spontaneous paroxysmal or persistent AF and analyzed. The bi-atrial DF maps were reconstructed by coupling 5-second BSPM with CT-determined patient geometry. The CEI results were compared with ablation sites and DFs found from BSPMs.
Results
CEI imaged left-to-right maximal frequency gradient (7.42 ± 0.66 Hz vs. 5.85 ± 1.2 Hz, LA vs. RA, p<0.05) in paroxysmal AF patients. Patients with persistent AF were imaged with a loss of the intra-chamber frequency gradient and a dispersion of the fast sources in both chambers. CEI was able to capture the AF behaviors, which were characterized by short-term stability, dynamic transition, and spatial repetition of the highest DF sites. The imaged highest DF sites were consistent with ablation sites in patients studied.
Conclusions
The frequency-based CEI allows localization of AF drivers with highest DF and characterization of the spatiotemporal frequency behaviors, suggesting the possibility for individualizing treatment strategy and advancing understanding of the underlying AF mechanisms. Significance: The establishment of noninvasive imaging techniques localizing AF drivers would facilitate management of this significant cardiac arrhythmia.
doi:10.1109/TBME.2016.2553641
PMCID: PMC5063686  PMID: 27093312
Atrial fibrillation; Cardiac electrical source imaging; Dominant frequency; Body surface potential mapping; Catheter ablation
5.  Impaired chronotropic response to physical activities in heart failure patients 
Background
While exercise-based cardiac rehabilitation has a beneficial effect on heart failure hospitalization and mortality, it is limited by the presence of chronotropic incompetence (CI) in some patients. This study explored the feasibility of using wearable devices to assess impaired chronotropic response in heart failure patients.
Methods
Forty patients with heart failure (left ventricular ejection fraction, LVEF: 44.6 ± 5.8; age: 54.4 ± 11.7) received ECG Holter and accelerometer to monitor heart rate (HR) and physical activities during symptom-limited treadmill exercise testing, 6-min hall walk (6MHW), and 24-h daily living. CI was defined as maximal HR during peak exercise testing failing to reach 70% of age-predicted maximal HR (APMHR, 220 – age). The correlation between HR and physical activities in Holter-accelerometer recording was analyzed.
Results
Of 40 enrolled patients, 26 were able to perform treadmill exercise testing. Based on exercise test reports, 13 (50%) of 26 patients did not achieve at least 70% of APMHR (CI patients). CI patients achieved a lower % APMHR (62.0 ± 6.3%) than non-CI patients who achieved 72.0 ± 1.2% of APMHR (P < 0.0001). When Holter-accelerometer recording was used to assess chronotropic response, the percent APMHR achieved during 6MHW and physical activities was significantly lower in CI patients than in non-CI patients. CI patients had a significantly shorter 6MHW distance and less physical activity intensity than non-CI patients.
Conclusion
The study found impaired chronotropic response in 50% of heart failure patients who took treadmill exercise testing. The wearable Holter-accelerometer recording could help to identify impaired chronotropic response to physical activities in heart failure patients.
Trial registration
ClinicalTrials.gov ID NCT02358603. Registered 16 May 2014.
doi:10.1186/s12872-017-0571-9
PMCID: PMC5445286  PMID: 28545575
Chronotropic incompetence; Heart rate; Heart failure rehabilitation; Treadmill exercise testing; 6 min hall walk
6.  Global Bi-ventricular endocardial distribution of activation rate during long duration ventricular fibrillation in normal and heart failure canines 
Background
The objective of this study was to detect differences in the distribution of the left and right ventricle (LV & RV) activation rate (AR) during short-duration ventricular fibrillation (SDVF, <1 min) and long-duration ventricular fibrillation VF (LDVF, >1 min) in normal and heart failure (HF) canine hearts.
Methods
Ventricular fibrillation (VF) was electrically induced in six healthy dogs (control group) and six dogs with right ventricular pacing-induced congestive HF (HF group). Two 64-electrode basket catheters deployed in the LV and RV were used for global endocardium electrical mapping. The AR of VF was estimated by fast Fourier transform analysis from each electrode.
Results
In the control group, the LV was activated faster than the RV in the first 20 s, after which there was no detectable difference in the AR between them. When analyzing the distribution of the AR within the bi-ventricles at 3 min of LDVF, the posterior LV was activated fastest, while the anterior was slowest. In the HF group, a detectable AR gradient existed between the two ventricles within 3 min of VF, with the LV activating more quickly than the RV. When analyzing the distribution of the AR within the bi-ventricles at 3 min of LDVF, the septum of the LV was activated fastest, while the anterior was activated slowest.
Conclusions
A global bi-ventricular endocardial AR gradient existed within the first 20 s of VF but disappeared in the LDVF in healthy hearts. However, the AR gradient was always observed in both SDVF and LDVF in HF hearts. The findings of this study suggest that LDVF in HF hearts can be maintained differently from normal hearts, which accordingly should lead to the development of different management strategies for LDVF resuscitation.
doi:10.1186/s12872-017-0530-5
PMCID: PMC5390480  PMID: 28407744
Ventricular Fibrillation; Activation Rate; Heart Failure
7.  Effect of surgical margin in R0 hepatectomy on recurrence-free survival of patients with solitary hepatocellular carcinomas without macroscopic vascular invasion 
Medicine  2016;95(44):e5251.
Abstract
The study aimed to investigate the impact of different surgical margins on recurrence-free survival (RFS) of patients with solitary hepatocellular carcinoma (HCC) without macroscopic vascular invasion.
The data of 586 selected patients who underwent curative hepatectomy for HCC between 2001 and 2012 were analyzed. The patients were divided into the anatomic resection and the nonanatomic resection groups according to the surgical approaches. Each group was further divided into group A (surgical margin <5 mm), group B (5 mm ≤ surgical margin < 10 mm), and group C (surgical margin ≥10 mm). Relationship between surgical margins and RFS in different groups was established by receiver operating characteristic curve and Kaplan–Meier analyses.
The RFS of the anatomic resection group was significantly longer than that of the nonanatomic resection group (P = 0.026). There were no statistical differences in RFS between groups A, B, and C (PA VS B = 0.512, PA VS C = 0.272, PB VS C = 0.822, nA = 38, nB = 43, nC = 80) in the anatomic resection group while in the nonanatomic resection group, RFSs of groups B and C were longer than that of group A (PA VS B = 0.009, PA VS C = 0.000, PB VS C = 0.505, nA = 151, nB = 119, nC = 155).
The analytic results suggest that if the patients with solitary HCC without macroscopic vascular invasion fall in the anatomic resection group, a minimal surgical margin (≥0 mm) is probably appropriate for hepatectomy; however, in cases of the nonanatomic resection, a surgical margin ≥5 mm should be regarded suitable for surgery of HCC.
doi:10.1097/MD.0000000000005251
PMCID: PMC5591133  PMID: 27858885
anatomic resection; hepatocellular carcinoma; nonanatomic resection; prognosis; recurrence; surgical margin
8.  Noninvasive Imaging of Human Atrial Activation during Atrial Flutter and Normal Rhythm from Body Surface Potential Maps 
PLoS ONE  2016;11(10):e0163445.
Background
Knowledge of atrial electrophysiological properties is crucial for clinical intervention of atrial arrhythmias and the investigation of the underlying mechanism. This study aims to evaluate the feasibility of a novel noninvasive cardiac electrical imaging technique in imaging bi-atrial activation sequences from body surface potential maps (BSPMs).
Methods
The study includes 7 subjects, with 3 atrial flutter patients, and 4 healthy subjects with normal atrial activations. The subject-specific heart-torso geometries were obtained from MRI/CT images. The equivalent current densities were reconstructed from 208-channel BSPMs by solving the inverse problem using individual heart-torso geometry models. The activation times were estimated from the time instant corresponding to the highest peak in the time course of the equivalent current densities. To evaluate the performance, a total of 32 cycles of atrial flutter were analyzed. The imaged activation maps obtained from single beats were compared with the average maps and the activation maps measured from CARTO, by using correlation coefficient (CC) and relative error (RE).
Results
The cardiac electrical imaging technique is capable of imaging both focal and reentrant activations. The imaged activation maps for normal atrial activations are consistent with findings from isolated human hearts. Activation maps for isthmus-dependent counterclockwise reentry were reconstructed on three patients with typical atrial flutter. The method was capable of imaging macro counterclockwise reentrant loop in the right atrium and showed inter-atria electrical conduction through coronary sinus. The imaged activation sequences obtained from single beats showed good correlation with both the average activation maps (CC = 0.91±0.03, RE = 0.29±0.05) and the clinical endocardial findings using CARTO (CC = 0.70±0.04, RE = 0.42±0.05).
Conclusions
The noninvasive cardiac electrical imaging technique is able to reconstruct complex atrial reentrant activations and focal activation patterns in good consistency with clinical electrophysiological mapping. It offers the potential to assist in radio-frequency ablation of atrial arrhythmia and help defining the underlying arrhythmic mechanism.
doi:10.1371/journal.pone.0163445
PMCID: PMC5051739  PMID: 27706179
9.  Combined measurements of tumor number and size helps estimate the outcome of resection of Barcelona clinic liver cancer stage B hepatocellular carcinoma 
BMC Surgery  2016;16:22.
Background
Although the Barcelona Clinic Liver Cancer (BCLC) staging system suggests that patients with stage B hepatocellular carcinoma (HCC) should be treated with transcatheter arterial chemoembolization instead of surgical treatment, recent studies indicated that the prognosis of surgical resection for patients with BCLC stage B HCC was better than that of TACE. However, the portion of patients with stage B that will achieve better outcomes from surgical treatment remains unclear. In this study, we identified risk factors that influence the prognosis of BCLC stage B HCC after R0 surgical resection to determine whether some patients with stage B HCC may benefit more from R0 resection than other patients and to provide a guideline to estimate the tendency.
Methods
The clinical data of 78 patients with BCLC stage B HCC after R0 surgical treatment within 11 years were analyzed retrospectively, using relapse or death as the endpoint. Kaplan-Meier survival and Cox regression analyses were used to study prognosis (disease-free survival, DFS and overall survival, OS) and independent risk factors.
Results
For all stage B patients, 1-, 2-, and 5-year DFS rates were 62.5, 36.4, and 16.6 %, respectively. Cumulative tumor size >5.0 cm and tumor number ≥4 were independent prognostic risk factors for DFS. The 1-, 2-, and 5- year DFS rates and OS rates of patients with at least one of these two factors were 49.0, 17.2, and 7.4 % (for DFS), and 78.6, 54.8, and 13.4 % (for OS), respectively, which were significantly lower than patients without these two factors (77.8, 58.3, and 27.2 % for DFS, and 94.4, 83.3,and 51.8 % for OS, respectively, P < 0.01).
Conclusions
The analyses indicated that the outcomes of R0 resection were much better for patients with BCLC stage B HCC with two or three tumors and cumulative tumor sizes of ≤5.0 but >3.0 cm than other patients with stage B.
doi:10.1186/s12893-016-0135-4
PMCID: PMC4837634  PMID: 27094483
BCLC staging; Hepatocellular carcinoma; Prognosis; R0 surgical treatment; Risk factors
10.  Exploring association between gastrointestinal heat retention syndrome and recurrent respiratory tract infections in children: a prospective cohort study 
Background
Recurrent respiratory tract infections (RRTIs) have a negative impact on both children’s health and family wellbeing. Deficiency of ZhengQi used to be an instinct factor driving RRTI in Traditional Chinese Medicine (TCM). Our clinical observations suggest that children with gastrointestinal heat retention syndrome (GHRS) may have a greater risk of catching respiratory tract infections (RTIs). GHRS is a new predisposing factor for RRTI and it is dietary related. This study is aimed to explore association between GHRS and RRTI.
Methods
A prospective cohort study has been conducted in Beijing, China; children aged 1–18 were enrolled. TCM symptoms, demographic and physiological characteristics were recorded by using semi-structured questionnaire. GHRS was considered as a predisposing factor. Children were followed up for next 12 months. We contacted with their parents using a face-to-face questionnaire survey, via email or phone every 3 months. Episodes of RTIs were recorded in detail.
Results
Three hundred thirty four children were enrolled and 307 (91.92 %) followed up for 12 months. The incidence of RTI was 4.32 episodes per child-year (95 % CI 4.03–4.61). 69 (43.13 %) children in the group with GHRS suffered from RRTI; there were 48 (32.65 %) children in group without GHRS. The risk ratio (RR) value of RRTI occurrence was 1.32 (95 % CI 0.91–1.91, P = 0.139), and the attributable risk percent (AR%) was 24.28 %. Dry stool and irritability were positively correlated with RTI episodes, age and BMI were negatively correlated with RTI episodes in a linear regression model. Dry stool (OR = 1.510) was positively correlated with RRTI occurrence, age (OR = 0.889) and BMI (OR = 0.858) were negatively correlated with RRTI occurrence in our logistic regression model.
Conclusions
GHRS is associated with RRTI in this cohort. Dry stool was positively associated with RRTI, and BMI was negatively associated with RRTI. Studies with larger sample size and longer follow up are needed to further evaluate this association. Relieving GHRS should be considered when TCM practitioners treat RRTI children, and this may protect children from suffering RTIs.
Trial registration
Chinese Clinical Trial Registry Number: ChiCTR-CCH-13003756
doi:10.1186/s12906-016-1062-8
PMCID: PMC4769561  PMID: 26921252
Gastrointestinal heat retention syndrome; Recurrent respiratory tract infection; Children; Prospective cohort study
11.  Relationship of different surgical margins with recurrence-free survival in patients with hepatocellular carcinoma 
To investigate the impact of different surgical margin and recurrence-free survival in patients with hepatocellular carcinoma (HCC). The data of 601 patients who underwent curative hepatectomy for HCC between January 1997 and December 2009 were analyzed. Milan group and exceeding Milan group were divided according to the Milan Criteria. Each of them was divided into 3 groups: group A (surgical margin ≤ 1 mm), group B (1 mm < surgical margin ≤ 9 mm) and group C (surgical margin ≥ 10 mm). The relationship between surgical margin and recurrence-free survival in different groups was analyzed. In Milan group recurrence-free survival of group C was more than group B and group B more than group A (P < 0.05). And in the exceeding Milan group recurrence-free surgical of group B was more than group A. There were no statistic differences within groups of B and C. Enlarging surgical margin may increase recurrence-free survival in HCC under Milan criteria.1mm in cases of exceeding Milan criteria may be regarded as the suitable surgical margin for operation of HCC.
PMCID: PMC4440187  PMID: 26045878
Surgical margin; hepatocellular carcinoma; recurrence-free survival; prognosis
12.  Salidroside alleviates paraquat-induced rat acute lung injury by repressing TGF-β1 expression 
Objective: This study was designed to investigate the protective effects of salidroside (SDS) via suppressing the expression of transforming growth factor-β1 (TGF-β1) in rat acute lung injury (ALI) induced by paraquat (PQ) and to explore the potential molecular mechanisms. Methods: A total of 90 male rats (190-210 g) were randomly and evenly divided into 9 groups: control group, PQ groups (4 groups), and PQ + SDS groups (4 groups). The rats in control group were treated with equal volume of saline intraperitoneally. The rats in PQ groups were exposed to PQ solution (20 mg/kg) by gastric gavage for 1, 6, 24, and 72 hours, respectively. The rats in PQ + SDS groups were intraperitoneally injected once with SDS (10 mg/kg) every 12 hours after PQ perfusion. Pulmonary pathological changes were observed by hematoxylin and eosin (HE) staining. The expression of TGF-β1 and the mRNA were evaluated by immunohistochemical (IHC) scoring and real time quantitative reverse transcription polymerase chain reaction (real-time qRT-PCR), respectively. Results: SDS alleviated the symptoms of PQ induced ALI. Moreover, SDS reduced the expression of the inflammatory cytokine TGF-β1 including TGF-β1 IHC scores (at each time point from 6 to 72 hours after PQ perfusion) and mRNA level (at each time point from 1 to 72 hours after PQ perfusion) compared with PQ groups (P < 0.05). Conclusion: SDS alleviated the pulmonary symptoms of PQ-induced ALI, at least partially, by repressing inflammatory cell infiltration and the expression of TGF-β1 resulting in delayed lung fibrosis.
PMCID: PMC4313990  PMID: 25674253
Salidroside; paraquat; acute lung injury; transforming growth factor-β1
13.  Endocardial focal activation originating from Purkinje fibers plays a role in the maintenance of long duration ventricular fibrillation 
Croatian Medical Journal  2014;55(2):121-127.
Aim
To determine the role of repetitive endocardial focal activations and Purkinje fibers in the maintenance of long duration ventricular fibrillation (LDVF, VF>1 minute) in canine hearts in vivo.
Methods
The study was conducted in electrophysiological laboratory of Shanghai Ruijin hospital from July 2010 to August 2012. A 64-electrode basket was introduced through a carotid artery into the left ventricle (LV) of 11 beagle dogs for global endocardial electrical mapping. In the Lugol’s solution group (n = 5), the subendocardium was ablated by washing with Lugol’s solution. In the control group, (n = 6) saline was used for ablation. Before and after saline or Lugol ablation, we determined QRS duration and QT/QTc interval in sinus rhythm (SR). We also measured the activation rates in the first 2 seconds of each minute during 7 minutes of VF for each group. If VF terminated spontaneously in less than 7 minutes, the VF segments used in activation rate analysis were reduced accordingly.
Results
At the beginning of VF there was no difference between the groups in the activation rate. However, after 1 minute of LDVF the Lugol’s solution group had significantly slower activation rate than the control group. In the control group, all episodes of LDVF (6/6) were successfully sustained for 7 minutes, while in the Lugol’s solution group 4/5 episodes of LDVF spontaneously terminated before 7 minutes (4.8 ± 1.4 minutes) (P = 0.015). In the control group, at 5.1 ± 1.3 minutes of LDVF, a successive, highly organized focal LV endocardial activation pattern was observed. During this period, activations partly arose in PF and spread to the working ventricular myocardium. Mapping analysis showed that these events were consistent with repetitive endocardial focal activations. No evidence of similar focal activations was observed in the Lugol’s solution group.
Conclusions
Repetitive endocardial focal activations in the LV endocardium may be associated with activation of subendocardial PFs. This mechanism may play an important role in the maintenance of LDVF.
doi:10.3325/cmj.2014.55.121
PMCID: PMC4009712  PMID: 24778098
14.  Recombinant adenovirus vector-mediated human MDA-7 gene transfection suppresses hepatocellular carcinoma growth in a mouse xenograft model☆ 
Journal of Biomedical Research  2012;26(1):53-58.
Hepatocellular carcinoma is one of the most common tumors in the world. The purpose of the present study was to investigate the inhibitory effects of adenoviral transduction of human melanoma differentiation-associated gene-7 (MDA-7) gene on hepatocellular carcinoma, so as to provide a theoretical basis for gene therapy of the disease. The human MDA-7 gene was cloned into replication-defective adenovirus specific to HepG2 cells using recombinant virus technology. RT-PCR and Western blotting assays were used to determine the expression of human MDA-7 mRNA and MDA-7 protein in HepG2 cells in vitro. Induction of apoptosis by overexpression of the human MDA-7 gene was determined by flow cytometry. In-vivo efficacy of adenoviral delivery of the human MDA-7 gene was assessed in nude mice bearing HepG2 cell lines in vivo by determining inhibition of tumor growth, VEGF and CD34 expression, and microvascular density (MVD). The results showed that AdGFP/MDA-7 induced apoptosis of HepG2 cells in vitro and significantly inhibited tumor growth in vivo (P < 0.05). The intratumoral MVD decreased significantly in the treated tumors (P < 0.05). We conclude the recombination adenovirus AdGFP/MDA-7 can effectively express biologically active human MDA-7, which leads to inhibition of hepatocellular carcinoma growth.
doi:10.1016/S1674-8301(12)60007-4
PMCID: PMC3596080  PMID: 23554730
MDA-7; adenovirus; hepatocellular carcinoma; gene therapy; angiogenesis
15.  Endothelial cells regulate cardiomyocyte development from embryonic stem cells 
Journal of cellular biochemistry  2010;111(1):29-39.
The molecules and environment to direct pluripotent stem cell differentiation into cardiomyocytes are largely unknown. Here, we determined a critical role of receptor tyrosine kinase, EphB4, in regulating cardiomyocyte generation from embryonic stem (ES) cells through endothelial cells. The number of spontaneous contracting cardiomyocytes, and the expression of cardiac-specific genes, including α-MHC and MLC-2V, was significantly decreased in EphB4-null ES cells. The peptide blocking study indicated that EphB4 signaling is critical for cardiomyocyte development in the early phase of ES cell differentiation. EphB4 was expressed in endothelial cells underneath contracting cardiomyocytes, but not in cardiomyocytes. Angiogenic inhibitors, including endostatin and angiostatin, inhibited endothelial cell differentiation and diminished cardiomyogenesis in ES cells. Generation of functional cardiomyocytes and the expression of cardiac-specific genes were significantly enhanced by co-culture of ES cells with human endothelial cells. Furthermore, the defects of cardiomyocyte differentiation in EphB4-deficient ES cells were rescued by human endothelial cells. For the first time, our study demonstrated that endothelial cells play an essential role in facilitating cardiomyocyte differentiation from pluripotent stem cells. EphB4 signaling is a critical component of the endothelial niche to regulate regeneration of cardiomyocytes.
doi:10.1002/jcb.22680
PMCID: PMC2930113  PMID: 20506197
embryonic stem (ES) cells; cardiomyocytes; endothelial cells; EphB4; ephrin
16.  Slug enhances invasion ability of pancreatic cancer cells through upregulation of matrix metalloproteinase-9 and actin cytoskeleton remodeling 
Slug, a member of the Snail family of transcription factors, has a crucial role in the regulation of epithelial-mesenchymal transition (EMT) by suppressing several epithelial markers and adhesion molecules, including E-cadherin. A recent study demonstrated that no relationship exists between Slug and E-cadherin in pancreatic cancer. Another study showed that in malignant mesothelioma effusions Slug was associated with matrix metalloproteinase (MMP) expression, but that there was no association with E-cadherin. F-ascin is an actin-bundling protein involved in filopodia assembly and cancer invasion and metastasis of multiple epithelial cancer types. In this study, we investigated Slug, E-cadherin, and MMP-9 expression using immunohistochemistry in 60 patients with pancreatic cancer and their correlation with carcinoma invasion and metastasis. Additionally, we observed the effects of Slug on invasion and metastasis in the pancreatic cancer cell line PANC-1. Alterations in Slug, MMP-9, and E-cadherin were determined by RT-PCR, western blot, and immunohistochemistry. Alterations in MMP-9 and F-actin cytoskeleton were determined by immunofluorescence staining, flow cytometry (FCM), or gelatin zymography. Slug, E-cadherin, and MMP-9 expression in pancreatic cancer was significantly associated with lymph node metastases and we found a significant correlation between Slug and MMP-9 expression; however, no significant correlation was observed between Slug and E-cadherin expression. Slug transfection significantly increased invasion and metastasis in PANC-1 cells and orthotopic tumor of mouse in vivo, and significantly upregulated and activated MMP-9; however, there was no effect on E-cadherin expression. Slug promoted the formation of lamelliopodia or filopodia in PANC-1 cells. The intracellular F-actin and MMP-9 was increased and relocated to the front of the extending pseudopodia from the perinuclear pool in Slug-transfected PANC-1 cells. These results suggest that Slug promotes migration and invasion of PANC-1 cells, which may correlate with the reorganization of MMP-9 and remodeling of the F-actin cytoskeleton, but not with E-cadherin expression.
doi:10.1038/labinvest.2010.201
PMCID: PMC3125102  PMID: 21283078
E-cadherin; epithelial-mesenchymal transition; F-actin cytoskeleton; matrix metalloproteinase; metastasis; pancreatic carcinoma; Slug

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