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1. Perioperative Changes in Plasma Nitrite and IL-6 Levels Predict Postoperative Atrial Fibrillation (POAF) and Acute Kidney Injury (AKI) after Cardiac Surgery.

Author

Fischer, Matthew, Howard-Quijano, Kimberly, Zong, Nobel, Youn, Ji, Liu, Norika, Scovotti, Jennifer, Grogan, Tristan, Mahajan, Aman, and Cai, Hua

Subjects
ROS, acute kidney injury, atrial fibrillation, nitric oxide (NO), nitrite, post-operative complications
Abstract

Background: Postoperative atrial fibrillation (POAF) and acute kidney injury (AKI) are common yet significant complications after cardiac surgery, with incidences of up to 40% for each. Here, we assessed plasma nitrite and serum interleukin-6 (IL-6) levels before and after cardiac surgery to quantify the extent to which oxidative stress and inflammation contribute to POAF and AKI occurrence. Methods: We prospectively enrolled 206 cardiac surgical patients. Plasma nitrite and serum IL-6 levels were determined preoperatively and at 24 h, 48 h and 72 h postoperatively. The patients had continuous EKG monitoring for occurrence of POAF, while daily serum creatinine was measured for determination of stage 1 + AKI. Results: Postoperatively, 78 (38%) patients experienced AF, and 47 (23%) patients experienced stage 1 + AKI. POAF analysis: Age, ACE-inhibitor use, valve surgery and percent change in baseline plasma nitrite at 24 h postoperatively were associated with POAF in multiple logistic regression analysis. The inclusion of this new biomarker significantly improved the POAF prediction model (AUC 0.77 for clinical risk factors alone, to AUC 0.81). AKI analysis: A history of diabetes mellitus was associated with AKI in multiple logistic regression analysis, and the addition of preoperative IL-6 levels improved the prediction model for AKI occurrence (AUC 0.69 to AUC 0.74). Conclusions: We previously observed selective upregulation of NADPH oxidase isoform 4 (NOX4) in patients with AF, a critical causal role of NOX4 for AF in zebrafish and a robust inhibitory effect of nitric oxide (NO) on NOX4. Our data innovatively demonstrate that a reduction in circulating nitrite levels, likely implicative of elevated NOX4-mediated oxidative stress, independently associates with POAF and improves POAF prediction, whereas the inclusion of circulating IL-6 levels improves the prediction model for AKI. Therefore, therapeutic strategies to mitigate these pathophysiological sequalae of surgical stress may reduce the incidence of severe postoperative complications of POAF and AKI.

Published
2024

2. Correction: CEPC Technical Design Report: Accelerator

Author

Abdallah, Waleed, de Freitas, Tiago CarlosAdorno, Afanaciev, Konstantin, Ahmad, Shakeel, Ahmed, Ijaz, Ai, Xiaocong, Aleem, Abid, Altmannshofer, Wolfgang, Alves, Fabio, An, Weiming, An, Rui, Anderle, Daniele Paolo, Antusch, Stefan, Arai, Yasuo, Arbuzov, Andrej, Arhrib, Abdesslam, Ashry, Mustafa, Bai, Sha, Bai, Yu, Bai, Yang, Bairathi, Vipul, Balazs, Csaba, Bambade, Philip, Ban, Yong, Bandyopadhyay, Triparno, Bao, Shou-Shan, Barber, Desmond P., Bat, Ays¸e, Batozskaya, Varvara, Behera, Subash Chandra, Belyaev, Alexander, Bertucci, Michele, Bi, Xiao-Jun, Bi, Yuanjie, Bian, Tianjian, Bianchi, Fabrizio, Bieko¨tter, Thomas, Biglietti, Michela, Bilanishvili, Shalva, Binglin, Deng, Bodrov, Denis, Bogomyagkov, Anton, Bondarenko, Serge, Boogert, Stewart, Boonekamp, Maarten, Borri, Marcello, Bosotti, Angelo, Boudry, Vincent, Boukidi, Mohammed, Boyko, Igor, Bozovic, Ivanka, Bozzi, Giuseppe, Brient, Jean-Claude, Budzinskaya, Anastasiia, Bukhari, Masroor, Bytev, Vladimir, Cacciapaglia, Giacomo, Cai, Hua, Cai, Wenyong, Cai, Wujun, Cai, Yijian, Cai, Yizhou, Cai, Yuchen, Cai, Haiying, Cai, Huacheng, Calibbi, Lorenzo, Cang, Junsong, Cao, Guofu, Cao, Jianshe, Chance, Antoine, Chang, Xuejun, Chang, Yue, Chang, Zhe, Chang, Xinyuan, Chao, Wei, Chatrabhuti, Auttakit, Che, Yimin, Che, Yuzhi, Chen, Bin, Chen, Danping, Chen, Fuqing, Chen, Fusan, Chen, Gang, Chen, Guoming, Chen, Hua-Xing, Chen, Huirun, Chen, Jinhui, Chen, Ji-Yuan, Chen, Kai, Chen, Mali, Chen, Mingjun, Chen, Mingshui, Chen, Ning, Chen, Shanhong, Chen, Shanzhen, Chen, Shao-Long, Chen, Shaomin, Chen, Shiqiang, Chen, Tianlu, Chen, Wei, Chen, Xiang, Chen, Xiaoyu, Chen, Xin, Chen, Xun, Chen, Xurong, Chen, Ye, Chen, Ying, Chen, Yukai, Chen, Zelin, Chen, Zilin, Chen, Gang, Chen, Boping, Chen, Chunhui, Cheng, Hok Chuen, Cheng, Huajie, Cheng, Shan, Cheng, Tongguang, Chi, Yunlong, Chimenti, Pietro, Chiu, Wen Han, Cho, Guk, Chu, Ming-Chung, Chu, Xiaotong, Chu, Ziliang, Coloretti, Guglielmo, Crivellin, Andreas, Cui, Hanhua, Cui, Xiaohao, Cui, Zhaoyuan, D’Anzi, Brunella, Dai, Ling-Yun, Dai, Xinchen, Dai, Xuwen, De Maria, Antonio, De Filippis, Nicola, De La Taille, Christophe, De Mori, Francesca, De Sio, Chiara, Del Core, Elisa, Deng, Shuangxue, Deng, Wei-Tian, Deng, Zhi, Deng, Ziyan, Dev, Bhupal, Dewen, Tang, Di Micco, Biagio, Ding, Ran, Ding, Siqin, Ding, Yadong, Dong, Haiyi, Dong, Jianing, Dong, Jing, Dong, Lan, Dong, Mingyi, Dong, Xu, Dong, Yipei, Dong, Yubing, Dordevic, Milos, Drewes, Marco, Du, Mingxuan, Du, Mingxuan, Du, Qianqian, Du, Xiaokang, Du, Yanyan, Du, Yong, Du, Yunfei, Duan, Chun-Gui, Duan, Zhe, Dydyshka, Yahor, Egede, Ulrik, Elmetenawee, Walaa, Eo, Yun, Fan, Ka Yan, Fan, Kuanjun, Fan, Yunyun, Fang, Bo, Fang, Shuangshi, Fang, Yuquan, Farilla, Ada, Farinelli, Riccardo, Farooq, Muhammad, Golfe, Angeles Faus, Fazliakhmetov, Almaz, Fei, Rujun, Feng, Bo, Feng, Chong, Feng, Junhua, Feng, Xu, Feng, Zhuoran, ZhuoranFeng, Castillo, Luis Roberto Flores, Forest, Etienne, Fowlie, Andrew, Fox, Harald, Fu, Hai-Bing, Fu, Jinyu, Fuks, Benjamin, Funakoshi, Yoshihiro, Gabrielli, Emidio, Gan, Nan, Gang, Li, Gao, Jie, Gao, Meisen, Gao, Wenbin, Gao, Wenchun, Gao, Yu, Gao, Yuanning, Gao, Zhanxiang, Gao, Yanyan, Ge, Kun, Ge, Shao-Feng, Ge, Zhenwu, Geng, Li-Sheng, Geng, Qinglin, Geng, Chao-Qiang, Ghosh, Swagata, Gioiosa, Antonio, Gladilin, Leonid, Gong, Ti, Gori, Stefania, Gou, Quanbu, Grinstein, Sebastian, Gu, Chenxi, Guillermo, Gerardo, da Costa, Joao Guimaraes, Guo, Dizhou, Guo, Fangyi, Guo, Jiacheng, Guo, Jun, Guo, Lei, Guo, Lei, Guo, Xia, Guo, Xin-Heng, Guo, Xinyang, Guo, Yun, Guo, Yunqiang, Guo, Yuping, Guo, Zhi-Hui, Gutie´rrez-Rodríguez, Alejandro, Ha, Seungkyu, Habib, Noman, Hajer, Jan, Hammer, Francois, Han, Chengcheng, Han, Huayong, Han, Jifeng, Han, Liang, Han, Liangliang, Han, Ruixiong, Han, Yang, Han, Yezi, Han, Yuanying, Han, Tao, Hao, Jiankui, Hao, Xiqing, XiqingHao, He, Chuanqi, He, Dayong, He, Dongbing, He, Guangyuan, He, Hong-Jian, He, Jibo, He, Jun, He, Longyan, He, Xiang, He, Xiao-Gang, He, Zhenqiang, Heinemann, Klaus, Heinemeyer, Sven, Heng, Yuekun, Herna´ndez-Ruíz, María A., Hong, Jiamin, Hor, Yuenkeung, Hou, George W. S., Hou, Xiantao, Hou, Xiaonan, Hou, Zhilong, Hou, Suen, Hu, Caishi, Hu, Chen, Hu, Dake, Hu, Haiming, Hu, Jiagen, Hu, Jun, Hu, Kun, Hu, Shouyang, Hu, Yongcai, Hu, Yu, Hu, Zhen, Hua, Zhehao, Hua, Jianfei, Huang, Chao-Shang, Huang, Fa Peng, Huang, Guangshun, Huang, Jinshu, Huang, Ke, Huang, Liangsheng, Huang, Shuhui, Huang, Xingtao, Huang, Xu-Guang, Huang, Yanping, Huang, Yonggang, Huang, Yongsheng, Huang, Zimiao, Huanyuan, Chen, Huh, Changgi, Hui, Jiaqi, Huo, Lihua, Hussain, Talab, Hwang, Kyuyeong, Ioannisian, Ara, Iqbal, Munawar, Jackson, Paul, Jafarzade, Shahriyar, Jang, Haeun, Jang, Seoyun, Ji, Daheng, Ji, Qingping, Ji, Quan, Ji, Xiaolu, Jia, Jingguang, Jia, Jinsheng, Jia, Xuewei, Jia, Zihang, Jiang, Cailian, Jiang, Han Ren, Jiang, Houbing, Jiang, Jun, Jiang, Xiaowei, Jiang, Xin, Jiang, Xuhui, Jiang, Yongcheng, Jiang, Zhongjian, Jiang, Cheng, Jiao, Ruiqi, Jin, Dapeng, Jin, Shan, Jin, Song, Jin, Yi, Jis, Junji, Jung, Sunghoon, Kacarevic, Goran, Kajfasz, Eric, Kalinovskaya, Lidia, Kampf, Aleksei, Kang, Wen, Kang, Xian-Wei, Kang, Xiaolin, Karmakar, Biswajit, Ke, Zhiyong, Keloth, Rijeesh, Khan, Alamgir, Khanpour, Hamzeh, Khosonthongkee, Khanchai, KhanchaiKhosonthongkee, Kim, Bobae, Kim, Dongwoon, Kim, Mi Ran, Kim, Minsuk, Kim, Sungwon, Kim, On, Klasen, Michael, Ko, Sanghyun, Koop, Ivan, Kornienko, Vitaliy, Kortman, Bryan, Kozlov, Gennady, Kuang, Shiqing, Kumar, Mukesh, Kuo, Chia Ming, Kwok, Tsz Hong, Lagarde, Franc¸ois Sylvain Ren, Lai, Pei-Zhu, Laktineh, Imad, Lan, Xiaofei, Lan, Zuxiu, Lavezzi, Lia, Lee, Justin, Lee, Junghyun, Lee, Sehwook, Lei, Ge, Lemmon, Roy, Leng, Yongxiang, Leung, Sze Ching, Li, Hai Tao, Li, Bingzhi, Li, Bo, Li, Bo, Li, Changhong, Li, Chao, Li, Cheng, Li, Cheng, Li, Chunhua, Li, Cui, Li, Dazhang, Li, Dikai, Li, Fei, Li, Gang, Li, Gang, Li, Gang, Li, Gaosong, Li, Haibo, Li, Haifeng, Li, Hai-Jun, Li, Haotian, Li, Hengne, Li, Honglei, Li, Huijing, Li, Jialin, Li, Jingyi, Li, Jinmian, Li, Jun, Li, Leyi, Li, Liang, Li, Ling, Li, Mei, Li, Meng, 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Liu, Tao, Liu, Tong, Liu, Wei, Liu, Xiang, Liu, Xiao-Hai, Liu, Xiaohui, Liu, Xiaoyu, Liu, Xin, Liu, Xinglin, Liu, Xingquan, Liu, Yang, Liu, Yanlin, Liu, Yao-Bei, Liu, Yi, Liu, Yiming, Liu, Yong, Liu, Yonglu, Liu, Yu, Liu, Yubin, Liu, Yudong, Liu, Yulong, Liu, Zhaofeng, Liu, Zhen, Liu, Zhenchao, Liu, Zhi, Liu, Zhi-Feng, Liu, Zhiqing, Liu, Zhongfu, Liu, Zuowei, Liu, Mia, Liu, Zhen, Liu, Xiaoyang, Lou, Xinchou, Lu, Cai-Dian, Lu, Jun-Xu, Lu, Qiu Zhen, Lu, Shang, Lu, Shang, Lu, Wenxi, Lu, Xiaohan, Lu, Yunpeng, Lu, Zhiyong, Lu, Xianguo, Lu, Wei, Lubsandorzhiev, Bayarto, Lubsandorzhiev, Sultim, Lukanov, Arslan, Luo, Jinliang, Luo, Tao, Luo, xiaoan, Luo, Xiaofeng, Luo, Xiaolan, Lv, Jindong, Lyu, Feng, Lyu, Xiao-Rui, Lyu, Kun-Feng, Ma, Ande, Ma, Hong-Hao, Ma, Jun-Li, Ma, Kai, Ma, Lishuang, Ma, Na, Ma, Renjie, Ma, Weihu, Ma, Xinpeng, Ma, Yanling, Ma, Yan-Qing, Ma, Yongsheng, Ma, Zhonghui, Ma, Zhongjian, Ma, Yang, Maity, Mousam, Mao, Lining, Mao, Yanmin, Mao, Yaxian, Martens, Aure´lien, Maria, Caccia Massimo Luigi, Matsumoto, Shigeki, Mellado, Bruce, Meloni, Davide, Men, Lingling, Meng, Cai, Meng, Lingxin, Mi, Zhenghui, Miao, Yuhui, Migliorati, Mauro, Ming, Lei, Mitsou, Vasiliki A., Monaco, Laura, Moraes, Arthur, Mosala, Karabo, Moursy, Ahmad, Mu, Lichao, Mu, Zhihui, Muchnoi, Nickolai, Muenstermann, Daniel, Muenstermann, Daniel, Munbodh, Pankaj, Murray, William John, Nanni, Jérôme, Nanzanov, Dmitry, Nie, Changshan, Nikitin, Sergei, Ning, Feipeng, Ning, Guozhu, Niu, Jia-Shu, Niu, Juan-Juan, Niu, Yan, Nkadimeng, Edward Khomotso, Ohmi, Kazuhito, Oide, Katsunobu, Okawa, Hideki, Ouchemhou, Mohamed, Ouyang, Qun, Paesani, Daniele, Pagani, Carlo, Paganis, Stathes, Pakuza, Collette, Pan, Jiangyang, Pan, Juntong, Pan, Tong, Pan, Xiang, Panda, Papia, Pandey, Saraswati, Pandurovic, Mila, Paparella, Rocco, Pasechnik, Roman, Passemar, Emilie, Pei, Hua, Peng, Xiaohua, Peng, Xinye, Peng, Yuemei, Ping, Jialun, Ping, Ronggang, Adhya, Souvik Priyam, Qi, Baohua, Qi, Hang, Qi, Huirong, Qi, Ming, Qian, Sen, Qian, Zhuoni, Qiao, Congfeng, Qin, Guangyou, Qin, Jiajia, Qin, Laishun, Qin, Liqing, Qin, Qin, Qin, Xiaoshuai, Qin, Zhonghua, Qu, Guofeng, Racioppi, Antonio, Ramsey-Musolf, Michael, Raza, Shabbar, Rekovic, Vladimir, Ren, Jing, Reuter, Ju¨rgen, Robens, Tania, Rossi, Giancarlo, Ruan, Manqi, Ruan, Manqi, Rumyantsev, Leonid, Ryu, Min Sang, Sadykov, Renat, Sang, Minjing, Sanz-Cillero, Juan Jose´, Saur, Miroslav, Savla, Nishil, Schmidt, Michael A., Sertore, Daniele, Settles, Ron, Sha, Peng, Shao, Ding-Yu, Shao, Ligang, Shao, Hua-Sheng, She, Xin, Shen, Chuang, Shen, Hong-Fei, Shen, Jian-Ming, Shen, Peixun, Shen, Qiuping, Shen, Zhongtao, Sheng, Shuqi, Shi, Haoyu, Shi, Hua, Shi, Qi, Shi, Shusu, Shi, Xiaolei, Shi, Xin, Shi, Yukun, Shi, Zhan, Shipsey, Ian, Shiu, Gary, Shu, Chang, Si, Zong-Guo, Sidorenkov, Andrei, Smiljanić, Ivan, Song, Aodong, Song, Huayang, Song, Jiaojiao, Song, Jinxing, Song, Siyuan, Song, Weimin, Song, Weizheng, Song, Zhi, Sourav, Shashwat, Spruzzola, Paolo, Su, Feng, Su, Shengsen, Su, Wei, Su, Shufang, Sui, Yanfeng, Sui, Zexuan, Sullivan, Michael, Sun, Baiyang, Sun, Guoqiang, Sun, Hao, Sun, Hao-Kai, Sun, Junfeng, Sun, Liang, Sun, Mengcheng, Sun, Pengfei, Sun, Sichun, Sun, Xianjing, Sun, Xiaohu, Sun, Xilei, Sun, Xingyang, Sun, Xin-Yuan, Sun, Yanjun, Sun, Yongzhao, Sun, Yue, Sun, Zheng, Sun, Zheng, Suwonjandee, Narumon, Eldin, Elsayed Tag, Tan, Biao, Tang, Bo, Tang, Chuanxiang, Tang, Gao, Tang, Guangyi, Tang, Jian, Tang, Jingyu, Tang, Liang, Tang, Ying’Ao, Tao, Junquan, Tawfik, Abdel Nasser, Taylor, Geoffrey, Telnov, Valery, Tian, Saike, Torre, Riccardo, Trzaska, Wladyslaw Henryk, Tsybychev, Dmitri, Tu, Yanjun, Tuo, Shengquan, Tytgat, Michael, Islam, Ghalib Ul, Ushakov, Nikita, Valencia, German, Velthuis, Jaap, Vicini, Alessandro, Vickey, Trevor, Vidakovic, Ivana, Videau, Henri, Volkas, Raymond, Voronin, Dmitry, Vukasinovic, Natasa, Wan, Xia, Wan, Xuying, Wang, Xiao, Wang, Anqing, Wang, Bin, Wang, Chengtao, Wang, Chuanye, Wang, Ci, Wang, Dayong, Wang, Dou, Wang, En, Wang, Fei, Wang, Fei, Wang, Guanwen, Wang, Guo-Li, Wang, Haijing, Wang, Haolin, Wang, Jia, Wang, Jian, Wang, Jianchun, Wang, Jianli, Wang, Jiawei, Wang, Jin, Wang, Jin-Wei, Wang, Joseph, Wang, Kechen, Wang, Lechun, Wang, Lei, Wang, Liguo, Wang, Lijiao, Wang, Lu, Wang, Meng, Wang, Na, Wang, Pengcheng, Wang, Qian, Wang, Qun, Wang, Shu Lin, Wang, Shudong, Wang, Taofeng, Wang, Tianhong, Wang, Tianyang, Wang, Tong, Wang, Wei, Wang, Wei, Wang, Xiaolong, Wang, Xiaolong, Wang, Xiaoning, Wang, Xiao-Ping, Wang, Xiongfei, Wang, Xujian, Wang, Yaping, Wang, Yaqian, Wang, Yi, Wang, Yiao, Wang, Yifang, Wang, Yilun, Wang, Yiwei, Wang, You-Kai, Wang, Yuanping, Wang, Yuexin, Wang, Yuhao, Wang, Yu-Ming, Wang, Yuting, Wang, Zhen, Wang, Zhigang, Wang, Weiping, Wang, Zeren Simon, Wang, Biao, Wang, Hui, Wang, Lian-Tao, Wang, Zihui, Wang, Zirui, Wang, Jia, Wang, Tong, Wei, Daihui, Wei, Shujun, Wei, Wei, Wei, Xiaomin, Wei, Yuanyuan, Wei, Yingjie, Wen, Liangjian, Wen, Xuejun, Wen, Yufeng, White, Martin, Williams, Peter, Wolffs, Zef, Womersley, William John, Wu, Baona, Wu, Bobing, Wu, Guanjian, Wu, Jinfei, Wu, Lei, Wu, Lina, Wu, Linghui, Wu, Minlin, Wu, Peiwen, Wu, Qi, Wu, Qun, Wu, Tianya, Wu, Xiang, Wu, Xiaohong, Wu, Xing-Gang, Wu, Xuehui, Wu, Yaru, Wu, Yongcheng, Wu, Yuwen, Wu, Zhi, Wu, Xin, Xia, Lei, Xia, Ligang, Xia, Shang, Xiang, Benhou, Xiang, Dao, Xiang, Zhiyu, Xiao, Bo-Wen, Xiao, Chu-Wen, Xiao, Dong, Xiao, Guangyan, Xiao, Han, Xiao, Meng, Xiao, Ouzheng, Xiao, Rui-Qing, Xiao, Xiang, Xiao, Yichen, Xiao, Ying, Xiao, Yu, Xiao, Yunlong, Xiao, Zhenjun, Xiao, Hengyuan, Xie, Nian, Xie, Yuehong, Xin, Tianmu, Xing, Ye, Xing, Zhizhong, Xu, Da, Xu, Fang, Xu, Fanrong, Xu, Haisheng, Xu, Haocheng, Xu, Ji, Xu, Miaofu, Xu, Qingjin, Xu, Qingnian, Xu, Wei, Xu, Wei, Xu, Weixi, Xu, Xinping, Xu, Zhen, Xu, Zijun, Xu, Zehua, Xu, Yaoyuan, Xue, Feifei, Yan, Baojun, Yan, Bin, Yan, Fen, Yan, Fucheng, Yan, Jiaming, Yan, Liang, Yan, Luping, Yan, Qi-Shu, Yan, Wenbiao, Yan, Yupeng, Yan, Luping, Yan, Haoyue, Yang, Dong, Yang, Fengying, Yang, Guicheng, Yang, Haijun, Yang, Jin Min, Yang, Jing, Yang, Lan, Yang, Li, Yang, Li Lin, Yang, Lili, Yang, Litao, Yang, Mei, Yang, Qiaoli, Yang, Tiansen, Yang, Xiaochen, Yang, Yingjun, Yang, Yueling, Yang, Zhengyong, Yang, Zhenwei, Yang, Youhua, Yang, Xiancong, Yao, De-Liang, Yao, Shi, Ye, Lei, Ye, Lingxi, Ye, Mei, Ye, Rui, Ye, Rui, Ye, Yecheng, Yermolchyk, Vitaly, Yi, Kai, Yi, Li, Yi, Yang, Yin, Di, Yin, Peng-Fei, Yin, Shenghua, Yin, Ze, Yin, Zhongbao, Yinhong, Zhang, Yoo, Hwi Dong, You, Zhengyun, Young, Charles, Yu, Boxiang, Yu, Chenghui, Yu, Fusheng, Yu, Jie-Sheng, Yu, Jinqing, Yu, Lingda, Yu, Zhao-Huan, Yu, Felix, Yu, Bingrong, Yuan, Changzheng, Yuan, Li, Yuan, Xing-Bo, Yuan, Youjin, Yue, Junhui, Yue, Qian, Yue, Baobiao, Zaib, Un Nisa, Zanzottera, Riccardo, Zeng, Hao, Zeng, Ming, Zhai, Jian, Zhai, Jiyuan, Zhai, Xin Zhe, Zhan, Xi-Jie, Zhang, Ben-Wei, Zhang, Bolun, Zhang, Di, Zhang, Guangyi, Zhang, Hao, Zhang, Hong-Hao, Zhang, Huaqiao, Zhang, Hui, Zhang, Jialiang, Zhang, Jianyu, Zhang, Jianzhong, Zhang, Jiehao, Zhang, Jielei, Zhang, Jingru, Zhang, Jinxian, Zhang, Junsong, Zhang, Junxing, Zhang, Lei, Zhang, Lei, Zhang, Liang, Zhang, Licheng, Zhang, Liming, Zhang, Linhao, Zhang, Luyan, Zhang, Mengchao, Zhang, Rao, Zhang, Shulei, Zhang, Wan, Zhang, Wenchao, Zhang, Xiangzhen, Zhang, Xiaomei, Zhang, Xiaoming, Zhang, Xiaoxu, Zhang, Xiaoyu, Zhang, Xuantong, Zhang, Xueyao, Zhang, Yang, Zhang, Yang, Zhang, Yanxi, Zhang, Yao, Zhang, Ying, Zhang, Yixiang, Zhang, Yizhou, Zhang, Yongchao, Zhang, Yu, Zhang, Yuan, Zhang, Yujie, Zhang, Yulei, Zhang, Yumei, Zhang, Yunlong, Zhang, Zhandong, Zhang, Zhaoru, Zhang, Zhen-Hua, Zhang, Zhenyu, Zhang, Zhichao, Zhang, Zhi-Qing, Zhang, Zhuo, Zhang, Zhiqing, Zhang, Cong, Zhang, Tianliang, Zhang, Luyan, Zhao, Guang, Zhao, Hongyun, Zhao, Jie, Zhao, Jingxia, Zhao, Jingyi, Zhao, Ling, Zhao, Luyang, Zhao, Mei, Zhao, Minggang, Zhao, Mingrui, Zhao, Qiang, Zhao, Ruiguang, Zhao, Tongxian, Zhao, Yaliang, Zhao, Ying, Zhao, Yue, Zhao, Zhiyu, Zhao, Zhuo, Zhemchugov, Alexey, Zheng, Hongjuan, Zheng, Jinchao, Zheng, Liang, Zheng, Ran, zheng, shanxi, Zheng, Xu-Chang, Zhile, Wang, Zhong, Weicai, Zhong, Yi-Ming, Zhou, Chen, Zhou, Daicui, Zhou, Jianxin, Zhou, Jing, Zhou, Jing, Zhou, Ning, Zhou, Qi-Dong, Zhou, Shiyu, Zhou, Shun, Zhou, Sihong, Zhou, Xiang, Zhou, Xingyu, Zhou, Yang, Zhou, Yong, Zhou, Yu-Feng, Zhou, Zusheng, Zhou, Demin, Zhu, Dechong, Zhu, Hongbo, Zhu, Huaxing, Zhu, Jingya, Zhu, Kai, Zhu, Pengxuan, Zhu, Ruilin, Zhu, Xianglei, Zhu, Yingshun, Zhu, Yongfeng, Zhuang, Xiao, Zhuang, Xuai, Zobov, Mikhail, Zong, Zhanguo, Zou, Cong, and Zou, Hongying

Published
2024
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3. Muon beamtest results of high-density glass scintillator tiles

Author

Du, Dejing, Liu, Yong, Cai, Hua, Chen, Danping, Hua, Zhehao, Han, Jifeng, Qi, Baohua, Qian, Sen, Ren, Jing, Sun, Xinyuan, Yang, Dong, Yin, Shenghua, and Zhang, Minghui

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment
Abstract

To achieve the physics goal of precisely measure the Higgs, Z, W bosons and the top quark, future electron-positron colliders require that their detector system has excellent jet energy resolution. One feasible technical option is the high granular calorimetery based on the particle flow algorithm (PFA). A new high-granularity hadronic calorimeter with glass scintillator tiles (GSHCAL) has been proposed, which focus on the significant improvement of hadronic energy resolution with a notable increase of the energy sampling fraction by using high-density glass scintillator tiles. The minimum ionizing particle (MIP) response of a glass scintillator tile is crucial to the hadronic calorimeter, so a dedicated beamtest setup was developed for testing the first batch of large-size glass scintillators. The maximum MIP response of the first batch of glass scintillator tiles can reach up to 107 p.e./MIP, which essentially meets the design requirements of the CEPC GSHCAL. An optical simulation model of a single glass scintillator tile has been established, and the simulation results are consistent with the beamtest results.

Published
2024

6. Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives

Author

Zhang, Xian-Bin, Fan, Yi-Bao, Jing, Rui, Getu, Mikiyas Amare, Chen, Wan-Ying, Zhang, Wei, Dong, Hong-Xia, Dakal, Tikam Chand, Hayat, Akhtar, Cai, Hua-Jun, Ashrafizadeh, Milad, Abd El-Aty, A. M., Hacimuftuoglu, Ahmet, Liu, Peng, Li, Tian-Feng, Sethi, Gautam, Ahn, Kwang Seok, Ertas, Yavuz Nuri, Chen, Min-Jiang, Ji, Jian-Song, Ma, Li, and Gong, Peng

Published
2024
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13. Cost-effectiveness analysis of different anesthesia strategies for transperineal MRI/US fusion prostate biopsy

Author

Di Jin, Xiao-Qi Kong, Ya-Juan Zhu, Zong-Xin Chen, Xi-Ming Wang, Cai-Hua Xu, Jin-Xian Pu, Jian-Quan Hou, Yu-Hua Huang, Fu-Hai Ji, and Chen Huang

Subjects
anesthesia strategy, cost-effectiveness analysis, economic evaluation, prostate biopsy, prostate cancer, Diseases of the genitourinary system. Urology, RC870-923
Abstract

This study aims to conduct a cost-effectiveness analysis of three different anesthesia strategies, namely chatting while under local anesthesia (Chat-LA), total intravenous anesthesia (TIVA), and general anesthesia with laryngeal mask airway (GA-LMA), employed in transperineal magnetic resonance imaging (MRI)/ultrasound (US) fusion prostate biopsy (TP-MUF-PB). A retrospective study was conducted involving 1202 patients who underwent TP-MUF-PB from June 2016 to April 2023 at The First Affiliated Hospital of Soochow University (Suzhou, China). Clinical data and outcomes, including total costs, complications, and quality-adjusted life years (QALYs), were compared. Probability sensitivity and subgroup analyses were also performed. Chat-LA was found to be the most cost-effective option, outperforming both TIVA and GA-LMA. However, subgroup analyses revealed that in younger patients (under 65 years old) and those with smaller prostate volumes (

Published
2024
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14. Asymptomatic atrial fibrillation among hospitalized patients: clinical correlates and in-hospital outcomes in Improving Care for Cardiovascular Disease in China-Atrial Fibrillation.

Author

Lin, Jing, Wu, Xue-Ying, Long, De-Yong, Jiang, Chen-Xi, Sang, Cai-Hua, Tang, Ri-Bo, Li, Song-Nan, Wang, Wei, Guo, Xue-Yuan, Ning, Man, Sun, Zhao-Qing, Yang, Na, Hao, Yong-Chen, Liu, Jun, Liu, Jing, Du, Xin, Smith, Sidney, Lip, Gregory, Zhao, Dong, Dong, Jian-Zeng, Ma, Chang-Sheng, and Fonarow, Gregg

Subjects
Acute coronary syndrome, Atrial fibrillation, Hypertension, Stroke, Humans, Male, Female, Atrial Fibrillation, Cardiovascular Diseases, Stroke, Ischemic Attack, Transient, Brain Ischemia, Cross-Sectional Studies, Quality Improvement, Prognosis, Risk Factors, Ischemic Stroke
Abstract

AIMS: The clinical correlates and outcomes of asymptomatic atrial fibrillation (AF) in hospitalized patients are largely unknown. We aimed to investigate the clinical correlates and in-hospital outcomes of asymptomatic AF in hospitalized Chinese patients. METHODS AND RESULTS: We conducted a cross-sectional registry study of inpatients with AF enrolled in the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation Project between February 2015 and December 2019. We investigated the clinical characteristics of asymptomatic AF and the association between the clinical correlates and the in-hospital outcomes of asymptomatic AF. Asymptomatic and symptomatic AF were defined according to the European Heart Rhythm Association score. Asymptomatic patients were more commonly males (56.3%) and had more comorbidities such as hypertension (57.4%), diabetes mellitus (18.6%), peripheral artery disease (PAD; 2.3%), coronary artery disease (55.5%), previous history of stroke/transient ischaemic attack (TIA; 17.9%), and myocardial infarction (MI; 5.4%); however, they had less prevalent heart failure (9.6%) or left ventricular ejection fractions ≤40% (7.3%). Asymptomatic patients were more often hospitalized with a non-AF diagnosis as the main diagnosis and were more commonly first diagnosed with AF (23.9%) and long-standing persistent/permanent AF (17.0%). The independent determinants of asymptomatic presentation were male sex, long-standing persistent AF/permanent AF, previous history of stroke/TIA, MI, PAD, and previous treatment with anti-platelet drugs. The incidence of in-hospital clinical events such as all-cause death, ischaemic stroke/TIA, and acute coronary syndrome (ACS) was higher in asymptomatic patients than in symptomatic patients, and asymptomatic clinical status was an independent risk factor for in-hospital all-cause death, ischaemic stroke/TIA, and ACS. CONCLUSION: Asymptomatic AF is common among hospitalized patients with AF. Asymptomatic clinical status is associated with male sex, comorbidities, and a higher risk of in-hospital outcomes. The adoption of effective management strategies for patients with AF should not be solely based on clinical symptoms.

Published
2023

16. Improving Empathetic Dialogue Generation by Dynamically Infusing Commonsense Knowledge

Author

Cai, Hua, Shen, Xuli, Xu, Qing, Shen, Weilin, Wang, Xiaomei, Ge, Weifeng, Zheng, Xiaoqing, and Xue, Xiangyang

Subjects
Computer Science - Computation and Language, Computer Science - Artificial Intelligence
Abstract

In empathetic conversations, individuals express their empathy towards others. Previous work has mainly focused on generating empathetic responses by utilizing the speaker's emotion. Besides, external commonsense knowledge has been applied to enhance the system's understandings of the speaker's situation. However, given an event, commonsense knowledge base contains various relations, potentially leading to confusion for the dialogue system. Consequently, inconsistencies arise among the emotion, generated response and speaker's contextual information. To this end, we propose a novel approach for empathetic response generation, which incorporates an adaptive module for commonsense knowledge selection to ensure consistency between the generated empathetic responses and the speaker's situation. This selected knowledge is used to refine the commonsense cognition and empathy expression for generated responses. Experimental results show that our approach significantly outperforms baseline models in both automatic and human evaluations, exhibiting the generation of more coherent and empathetic responses. Moreover, case studies highlight the interpretability of knowledge selection in the responses and the effectiveness of adaptive module in our model. Code: https://github.com/Hanscal/DCKS., Comment: Accepted by ACL 2023. arXiv admin note: substantial text overlap with arXiv:2109.05739 by other authors

Published
2023

17. Prokaryotic genome editing based on the subtype I-B-Svi CRISPR-Cas system

Author

Tong, Wang-Yu, Yong, De-Xiang, Xu, Xin, Qiu, Cai-Hua, Zhang, Yan, Yang, Xing-Wang, Xia, Ting-Ting, Liu, Qing-Yang, Cao, Su-Li, Sun, Yan, and Li, Xue

Subjects
Quantitative Biology - Genomics
Abstract

Type I CRISPR-Cas systems are the most common among six types of CRISPR-Cas systems, however, non-self-targeting genome editing based on a single Cas3 of type I CRISPR-Cas systems has not been reported. Here, we present the subtype I-B-Svi CRISPR-Cas system (with three confirmed CRISPRs and a cas gene cluster) and genome editing based on this system found in Streptomyces virginiae IBL14. Importantly, like the animal-derived bacterial protein SpCas9 (1368 amino-acids), the single, compact, non-animal-derived bacterial protein SviCas3 (771 amino-acids) can also direct template-based microbial genome editing through the target cell's own homology-directed repair system, which breaks the view that the genome editing based on type I CRISPR-Cas systems requires a full Cascade. Notably, no off-target changes or indel-formation were detected in the analysis of potential off-target sites. This discovery broadens our understanding of the diversity of type I CRISPR-Cas systems and will facilitate new developments in genome editing tools., Comment: 113 pages, 10 figures, and 6 tables

Published
2023

18. Constructing a model of MHD capacity overload and its clinical effectiveness

Author

Cai-hua Zeng, Ling-Ling Tao, Jing Cheng, Qin Huang, and Mei-rong Fan

Subjects
hemodialysis, ultrasound, routine blood biochemistry, maintenance hemodialysis, capacity overload, early warning model, clinical effectiveness, Internal medicine, RC31-1245
Abstract

ObjectiveTo construct an early warning model of maintenance hemodialysis （MHD） capacity overload based upon basic dialysis data, ultrasound and routine blood biochemistry and examine its clinical effectiveness. Methods From January 2023 to December 2023, 603 patients on MHD were retrospectively reviewed. They were assigned into two sets of modeling （n = 402） and validation （n = 201） according to a ratio of 2:1. The relevant clinical were collected. And the influencing factors of MHD capacity overload in modeling set were analyzed by univariate and LASSO-Logistic regression. The risk prediction nomogram model was constructed. And consistency index, calibration curve, receiver operating characteristic （ROC） curve and decision curve were utilized for verifying the prediction model internally and externally. Results Serum albumin, Kt/V, RRF and left ventricular ejection fraction （LVEF） in overload group were lower than those in normal group. NT-proBNP, ultrasonic lung B-line and right atrial diameter were higher than those in normal group （P＜0.05）. LASSO results indicated that serum albumin, Kt/V, RRF, LVEF, NT-proBNP, ultrasonic lung B-line and right atrial internal diameter were Top 7 characteristic variables of volume overload in MHD. Logistic regression results revealed that Kt/V, serum albumin, RRF and LVEF were the protective factors for MHD volume overload. And NT-proBNP, ultrasonic lung B-line and right atrial diameter were the risk factors for MHD volume overload （P＜0.05）. The risk prediction nomogram model of capacity overload was constructed according to the influencing factors of Logistic regression. Consistency index in modeling and validation sets was 0.860 and 0.814, respectively. Calibration curve showed that the incidence of MHD capacity overload predicted by the model in modeling and validation sets was basically consistent with the actual incidence. ROC curve indicated that the area under the curve as predicted by the model in modeling and validation sets was 0.917（95%CI: 0.886-0.948） and 0.916（95%CI: 0.869-0.962）. Decision curve revealed that when the high-risk threshold of modeling set was 0-0.7 and the high risk threshold of validation set 0-0.7. The model had an excellent clinical net benefit. Conclusion In MHD patients, the occurrence of volume overload is affected by serum albumin, Kt/V, RRF, LVEF, NT-proBNP, ultrasonic lung B-line and right atrial diameter. The early warning model built according to the factors related to volume overload has excellent predictive capability and clinical benefit.

Published
2024
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19. Analysis of special follow-up evaluation of oils and fats in national food safety standards from 2019 to 2021

Author

YANG Jingjin, YUAN Weijia, CAI Hua, XU Biyao, LUO Baozhang, QIN Luxin, SONG Xia, QIU Danping, ZHANG Nan, LIU Hong, and XU Yili

Subjects
national food safety standards, follow-up evaluation, oils and fats, Food processing and manufacture, TP368-456, Nutrition. Foods and food supply, TX341-641
Abstract

ObjectiveTo provide references for the formulation and revision of corresponding food standards and further improvement of China’s national food safety standard system， the implementation of national food safety standards for oils and fats was understood， and the suggestions and opinions in the implementation of food safety standards was collected.MethodsThe standard follow-up evaluation was carried out by means of enterprise background investigation， questionnaire survey， on-site investigation and expert consultation. Food production and marketing enterprises， supervision institutes， inspection and testing institutions， industry associations， and relevant scientific research institutes from Shanghai， Guangdong， Hebei， Jiangxi， Guangxi and Ningxia were selected as the subjects for questionnaire and on-site investigation. Collect the problems encountered in the implementation of product standards， specification， examination method standards， and general standards， as well as suggestions on the revision of standards and system construction.ResultsFrom 2019 to 2021， a total of 3 097 special follow-up evaluation questionnaires were issued， 1 348 valid questionnaires were recovered， the recovery rate was 43.53%. 183 enterprises were surveyed on the spot， and 72 valid opinions and suggestions were collected. Generally speaking， the respondents have a high degree of recognition of the national food safety standards for oils and fats， and the suggestions mainly focus on “improving food classification and definition” and “increasing or improving technical indicators”.ConclusionThe implementation of national food safety standards for oils and fats is satisfactory， but it is necessary to improve the terminology definitions and technical requirements of relevant standards.

Published
2024
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20. Morphology and location of thrombus and sludge in patients with non-valvular atrial fibrillation

Author

Jing Cui, Shi-Jun Xia, Ri-Bo Tang, Liu He, Xue-Yuan Guo, Song-Nan Li, Nian Liu, Cai-Hua Sang, De-Yong Long, Xin Du, Jian-Zeng Dong, and Chang-Sheng Ma

Subjects
Thrombus, Sludge, Morphology, Location, Atrial fibrillation, Transesophageal echocardiography, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Stroke and thromboembolism in nonvalvular atrial fibrillation (NVAF) primarily arise from thrombi or sludge in the left atrial appendage (LAA). Comprehensive insight into the characteristics of these formations is essential for effective risk assessment and management. Methods We conducted a single-center retrospective observational of 176 consecutive NVAF patients with confirmed atrial/appendage thrombus or sludge determined by a pre-ablation transesophageal echocardiogram (TEE) from December 2017 to April 2019. We obtained clinical and echocardiographic characteristics, including left atrial appendage emptying velocity (LAAeV) and filling velocity (LAAfV). Data analysis focused on identifying the morphology and location of thrombus or sludge. Patients were divided into the solid thrombus and sludge groups, and the correlation between clinical and echocardiographic variables and thrombotic status was analyzed. Results Morphological classification: In total, thrombi were identified in 78 patients, including 71 (40.3%) mass and 7 (4.0%) lamellar, while sludge was noted in 98 (55.7%). Location classification: 92.3% (72/78) of patients had thrombus confined to the LAA; 3.8% (3/78) had both LA and LAA involvement; 2.7% (2/78) had LA, LAA and RAA extended into the RA, the remained 1.2%(1/78) was isolated to RAA. 98.0% (96/98) of patients had sludge confined to the LAA; the remaining 2.0% (2/98) were present in the atrial septal aneurysm, which protrusion of interatrial septum into the RA. The thrombus and sludge groups showed low LAAeV (19.43 ± 9.59 cm/s) or LAAfV (17.40 ± 10.09 cm/s). Only LA dimension ≥ 40 mm was independently associated with the thrombus state in the multivariable model. Conclusion This cohort study identified rare thrombus morphology and systematically summarized the classification of thrombus morphology. The distribution of thrombus and sludge outside limited to LAA was updated, including bilateral atrial and appendage involvement and rare atrial septal aneurysm sludge. LAAeV and LAAfV were of limited value in distinguishing solid thrombus from sludge. Clinical Trial Number ChiCTR-OCH-13,003,729.

Published
2024
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21. Network pharmacology, experimental validation and pharmacokinetics integrated strategy to reveal pharmacological mechanism of goutengsan on methamphetamine dependence

Author

Han-Cheng Li, Jie-Yu Li, Xing-Chen Wang, Ming Zeng, Yang-Kai Wu, Yi-Ling Chen, Cai-Hua Kong, Ke-Lin Chen, Jie-Ru Wu, Zhi-Xian Mo, Jia-Xuan Zhang, and Chang-Shun Liu

Subjects
goutengsan, methamphetamine dependence, MAPK pathway, network pharmacology, pharmacokinetics, Therapeutics. Pharmacology, RM1-950
Abstract

BackgroundGoutengsan (GTS) is a traditional Chinese medicine formula that can improve multiple nervous system diseases, such as methamphetamine (MA) dependence. However, the mechanism how GTS treats MA dependence remains unclear. This study was aimed to investigate the action mechanism of GTS on MA dependence using network pharmacology, in vivo/in vitro experimental validation, pharmacokinetics, and tissue distribution in the brain.Materials and MethodsThe bioactive ingredients from GTS and possible targeted genes for treating MA dependence were predicted using network pharmacology. The binding of key components of GTS to the predicted proteins was studied using molecular docking, and the key components were verified by HPLC. The effects of GTS on an MA-induced model in rats and SH-SY5Y cells were studied. The regulatory effects of GTS on the expressions of predicted MAPK pathway-related proteins in rat brain tissues and SH-SY5Y cells were validated. Furthermore, the plasma exposure and brain tissue distribution of GTS ingredients for MA dependence treatment and MAPK pathway regulation were studied in mice.ResultsNetwork pharmacology screened 53 active ingredients, and 287 potential targets of GTS, and showed the MAPK pathway was among the most relevant pathways. Molecular docking showed that key active ingredients (e.g., 6-gingerol, liquiritin and rhynchophylline) bound strongly with MAPK core targets, such as MAPK3, and MAPK8. Five compounds of GTS were detected by HPLC, including 6-gingerol, chlorogenic acid, liquiritin, 5-o-methylviscumaboloside and hesperidin. GTS had a therapeutic effect on MA-dependent rats, and reduced hippocampal CA1 damage and relative expressions of p-MAPK3/MAPK3, p-MAPK8/MAPK8 in brain tissues induced by MA. GTS counteracted aberrant alterations in cAMP, 5-TH and cellular morphology induced by MA induction and exerts therapeutic effects on MA-induced SH-SY5Y cell models. GTS also can antagonize the high expressions of MAPK-related proteins in MA-induced SH-SY5Y cells. Pharmacokinetic experiment revealed the four ingredients of GTS (e.g., chlorogenic acid, 5-o-methylviscumaboloside, hesperidin and rhynchophylline) were exposed in the plasma and brain, which demonstrates its pharmacological effect on MA dependence.ConclusionGTS treats MA dependence by regulating the MAPK pathway via multiple bioactive ingredients. The network pharmacology, experimental validation and pharmacokinetics integrated strategy is efficient in discovering the key pharmacological mechanism of herbal formulae.

Published
2024
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22. Restoration of coronary microvascular function by OGA overexpression in a high-fat diet with low-dose streptozotocin-induced type 2 diabetic mice

Author

Cabrera, Jody Tori, Si, Rui, Tsuji-Hosokawa, Atsumi, Cai, Hua, Yuan, Jason X-J, Dillmann, Wolfgang H, and Makino, Ayako

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Diabetes, Cardiovascular, Nutrition, Heart Disease - Coronary Heart Disease, Heart Disease, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Animals, Mice, Acetylglucosaminidase, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Diet, High-Fat, Endothelial Cells, Streptozocin, cardiovascular disease, endothelial dysfunction, angiogenesis, tube formation, Pharmacology and Pharmaceutical Sciences, Medical Physiology, Endocrinology & Metabolism, Clinical sciences
Abstract

Sustained hyperglycemia results in excess protein O-GlcNAcylation, leading to vascular complications in diabetes. This study aims to investigate the role of O-GlcNAcylation in the progression of coronary microvascular disease (CMD) in inducible type 2 diabetic (T2D) mice generated by a high-fat diet with a single injection of low-dose streptozotocin. Inducible T2D mice exhibited an increase in protein O-GlcNAcylation in cardiac endothelial cells (CECs) and decreases in coronary flow velocity reserve (CFVR, an indicator of coronary microvascular function) and capillary density accompanied by increased endothelial apoptosis in the heart. Endothelial-specific O-GlcNAcase (OGA) overexpression significantly lowered protein O-GlcNAcylation in CECs, increased CFVR and capillary density, and decreased endothelial apoptosis in T2D mice. OGA overexpression also improved cardiac contractility in T2D mice. OGA gene transduction augmented angiogenic capacity in high-glucose treated CECs. PCR array analysis revealed that seven out of 92 genes show significant differences among control, T2D, and T2D + OGA mice, and Sp1 might be a great target for future study, the level of which was significantly increased by OGA in T2D mice. Our data suggest that reducing protein O-GlcNAcylation in CECs has a beneficial effect on coronary microvascular function, and OGA is a promising therapeutic target for CMD in diabetic patients.

Published
2023

25. Combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication

Author

Huang, Kai, Wu, Yusi, Zhang, Yixuan, Youn, Ji Youn, and Cai, Hua

Subjects
Biochemistry and Cell Biology, Medicinal and Biomolecular Chemistry, Chemical Sciences, Biological Sciences, Cardiovascular, Orphan Drug, Rare Diseases, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Animals, Mice, Angiotensin II, Aortic Aneurysm, Aortic Aneurysm, Abdominal, Disease Models, Animal, Folic Acid, Mice, Inbred C57BL, Nifedipine, Mice, Knockout, ApoE, Folic acid, Abdominal aortic aneurysm, Apolipoprotein E null mice, Endothelial nitric oxide synthase, uncoupling, Superoxide, Nitric oxide, Tetrahydrobiopterin(H4B), Oxidative stress, Reactive oxygen species, Vascular remodeling, Elastin degradation, Adventitial hypertrophy, Endothelial nitric oxide synthase (eNOS) uncoupling, Tetrahydrobiopterin (H(4)B), Medical Biochemistry and Metabolomics, Pharmacology and Pharmaceutical Sciences, Biochemistry and cell biology, Medicinal and biomolecular chemistry
Abstract

Aortic aneurysms are prevalent and severe vascular diseases with high mortality from unpredicted ruptures, while the only treatment option is surgical correction of large aneurysms with considerable risk. We have shown that folic acid (FA) is highly effective in alleviating development of aneurysms although not sufficient to completely attenuate aneurysm formation. Here, we examined therapeutic effects on aneurysms of combining FA with Nifedipine as novel and potentially more effective oral medication. Oral administration with FA (15 mg/kg/day) significantly reduced incidence of AAA from 85.71% to 18.75% in Ang II-infused apolipoprotein E (apoE) null mice, while combination of FA with Nifedipine (1.5, 5.0 or 20 mg/kg/day) substantially and completely further reduced incidence of AAA to 12.5%, 11.76% and 0.00% respectively in a dose-dependent manner. The combinatory therapy substantially and completely further alleviated enlargement of abdominal aortas defined by ultrasound, vascular remodeling characterized by elastin degradation and adventitial hypertrophy, as well as aortic superoxide production and eNOS uncoupling activity also in a dose-dependent manner, with combination of FA with 20 mg/kg/day Nifedipine attenuating all of these features by 100% to control levels. Aortic NO and H4B bioavailabilities were also dose-dependently further improved by combining FA with Nifedipine. These data establish entirely innovative and robust therapeutic regime of FA combined with Nifedipine for the treatment of aortic aneurysms. The comminatory therapy can serve as a first-in-class and most effective oral medication for aortic aneurysms, which can be rapidly translated into clinical practice to revolutionize management of the devastating vascular diseases of aortic aneurysms known as silent killers.

Published
2022

26. Longitudinal profiling in patients undergoing cardiac surgery reveals postoperative changes in DNA methylation.

Author

Fischer, Matthew A, Chapski, Douglas J, Soehalim, Elizabeth, Montoya, Dennis J, Grogan, Tristan, Pellegrini, Matteo, Cai, Hua, Shemin, Richard J, and Vondriska, Thomas M

Subjects
Humans, Postoperative Complications, Cardiac Surgical Procedures, Longitudinal Studies, DNA Methylation, Gene Expression Regulation, Atrial fibrillation, Cardiac surgery, DNA methylation, Precision medicine, Clinical Research, Cardiovascular, Heart Disease, Genetics, 2.1 Biological and endogenous factors, Aetiology, Clinical Sciences, Paediatrics and Reproductive Medicine
Abstract

BackgroundCardiac surgery and cardiopulmonary bypass induce a substantial immune and inflammatory response, the overactivation of which is associated with significant pulmonary, cardiovascular, and neurologic complications. Commensurate with the immune and inflammatory response are changes in the heart and vasculature itself, which together drive postoperative complications through mechanisms that are poorly understood. Longitudinal DNA methylation profiling has the potential to identify changes in gene regulatory mechanisms that are secondary to surgery and to identify molecular processes that predict and/or cause postoperative complications. In this study, we measure DNA methylation in preoperative and postoperative whole blood samples from 96 patients undergoing cardiac surgery on cardiopulmonary bypass.ResultsWhile the vast majority of DNA methylation is unchanged by surgery after accounting for changes in cell-type composition, we identify several loci with statistically significant postoperative changes in methylation. Additionally, two of these loci are associated with new-onset postoperative atrial fibrillation, a significant complication after cardiac surgery. Paired statistical analysis, use of FACS data to support sufficient control of cell-type heterogeneity, and measurement of IL6 levels in a subset of patients add rigor to this analysis, allowing us to distinguish cell-type variability from actual changes in methylation.ConclusionsThis study identifies significant changes in DNA methylation that occur immediately after cardiac surgery and demonstrates that these acute alterations in DNA methylation have the granularity to identify processes associated with major postoperative complications. This research also establishes methods for controlling for cell-type variability in a large human cohort that may be useful to deploy in other longitudinal studies of epigenetic marks in the setting of acute and chronic disease.

Published
2022

27. Diagnostic and predictive values of circulating tetrahydrobiopterin levels as a novel biomarker in patients with thoracic and abdominal aortic aneurysms

Author

Zhang, Yixuan, Siu, Kin Lung, Li, Qiang, Howard-Quijano, Kimberly, Scovotti, Jennifer, Mahajan, Aman, and Cai, Hua

Subjects
Biochemistry and Cell Biology, Medicinal and Biomolecular Chemistry, Chemical Sciences, Biological Sciences, Cardiovascular, Prevention, Rare Diseases, Clinical Research, Good Health and Well Being, Animals, Aortic Aneurysm, Abdominal, Aortic Aneurysm, Thoracic, Biomarkers, Biopterin, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Aortic aneurysm, Thoracic aortic aneurysm, Abdominal aortic aneurysm, Tetrahydrobiopterin(H4B), eNOS uncoupling, Human patients, Biomarker, Diagnosis, Prediction, Monitoring, Tetrahydrobiopterin (H(4)B), Medical Biochemistry and Metabolomics, Pharmacology and Pharmaceutical Sciences, Biochemistry and cell biology, Medicinal and biomolecular chemistry
Abstract

We have previously shown that circulating levels of tetrahydrobiopterin (H4B) function as a robust biomarker for aortic aneurysms in several independent animal models. In the present study, we examined diagnostic and predictive values of circulating H4B levels in human patients of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) for the first time, while clinically applicable biomarkers for aortic aneurysms have never been previously available. Ninety-five patients scheduled for TAA repair surgeries and 53 control subjects were recruited at University of California Los Angeles (UCLA) Ronald Regan Medical Center, while 44 control subjects and 29 AAA patients were recruited through National Institute of Health (NIH) National Disease Research Interchange (NDRI) program. We had intriguing observations that circulating H4B levels were substantially lower in TAA and AAA patients, linearly correlated with aortic H4B levels (blood: R = 0.8071, p

Published
2022

29. Optimal timing of anticoagulation after acute ischaemic stroke with atrial fibrillation (OPTIMAS): a multicentre, blinded-endpoint, phase 4, randomised controlled trial

Author

Jelley, Benjamin, Hughes, Tom, Evans, Mim, Esteban, Diego Garcia, Knibbs, Lucy, Broad, Lauren, Price, Rebecca, Griebel, Liz Hamer, Hewson, Sian, Thavanesan, Kamy, Mallon, Louise, Smith, Anna, White, Miranda, Zhang, Liqun, Clarke, Brian, Abousleiman, Youssif, Binnie, Lauren, Sim, Cai Hua, Castanheira, Margarida, Humphries, Fiona, Obarey, Sabaa, Feerick, Shez, Lee, Yee Chin, Lewis, Alex, Muhammad, Riham, Francia, Nina, Atang, Ndifreke, Banaras, Azra, Marinescu, Marilena, Ferdinand, Philip, Varquez, Resti, Ponce, Ida, Saxena, Surabhi, O'Brien, Eoin, Reyes, Juliana Delos, Mitchell-Douglas, Jennifer, Francis, Jobbin, Banerjee, Soma, Dave, Vaishali, Mashate, Sheila, Patel, Tulsi, Sekaran, Lakshmanan, Murad, Wahid, Asaipillai, Asokanathan, Sakthivel, Sethuraman, Tate, Margaret, Angus, Jane, Reid, Lisa, Fornolles, Caroline, Sundayi, Saul, Poolon, Lincy, Justin, Francis, Hunte, Sophy, Bhandari, Mohit, Kho, Jules, Cvoro, Vera, Parakramawansha, Ruwan, Couser, Mandy, Hughes, Hannah, Naqvi, Aaizza, Harkness, Kirsty, Richards, Emma, Howe, Jo, Kamara, Chris, Gardner, Jon, Bains, Harjit, Teal, Rachel, Joseph, Jeethu, Benjamin, Jithen, Al-Hussayni, Samer, Thomas, George, Robinson, Faye, Dixon, Lynn, Krishnan, Manju, Slade, Peter, Anjum, Tal, Storton, Sharon, Adie, Katja, Northcott, Keren, Morgan, Katie, Williams, Emilie, Chanashekar, Harinath, Maguire, Holly, Gabriel, Claire, Maren, Deborah, David, Hannah, Clarke, Sheron, Nagaratnam, Kiruba, Nelatur, Varun, Mannava, Neelima, Blasco, Lara, Devine, Joseph, Bathula, Rajaram, Gopi, Parvathy, Mehta, Niharika, Sreedevi Raj, Sreena, Teo, James, Sztriha, Laszio, Mah, Yee, Ankolekar, Sandeep, Sari, Beatrix, Tibajai, Maria, Morgan, Alicia, Recaman, Maria, Bayhonan, Samantha, Belo, Caroline, Finch, Sharon, Keenan, Samantha, Bowring, Angie, Shetty, Ashit, Chan, Siang, Gray, Lucy, Harrison, Thomas, Spooner, Oliver, Kinsella-Perks, Edward, Erumere, Esther, Sanders, Brittany, Sims, Don, Willmot, Mark, Littleton, Edward, Spruce, Elaine, Moody, Lisa, Sheriden, Christopher, Luxmore-Brown, Scott, Neal, Aoife, Beddows, Sophie, Tuna, Maria Assuncao, Misra, Amulya, Penn, Ruth, Mariampillai, Sonia, Anwar, Ijaz, Annamalai, Arunkumar, Whitehouse, Sarah, Shepherd, Lorna, Siddle, Elaine, Chatterjee, Kausik, Leason, Sandra, Davies, Angela, Marigold, Richard James, Frank, Sarah, Baird, Alix, Hannam-Penfold, Tomas, Inacio, Liliana, Smith, Simon, Eveson, David, Musarrat, Kashif, Khan, Shagufta, Harris, Tracy, Chowdhury, Muhibbur, Alam, Sajid, Jamieson, Elena, Anyankpele, Ebitare, Al Shalchi, Farah, Rivers, Vanessa, Bell, Stephanie, Francis, Rebecca, Beeby, Deborah, Finch, Jenny, Macleod, Mary Joan, Guzman-Gutierrez, German, Carter, Karla, Irvine, Janice, Gbadamoshi, Lukuman, Costa, Telma, Heirons, Sarah, Stoney, Hayley, Shaw, Louise, Choulerton, James, Catibog, Darwin, Sattar, Naweed, Myint, Min, Smith, Andy, Serac, Kwin, Emsley, Hedley, Sultan, Sulaiman, Gregary, Bindu, Brown, Allan, Mahmood, Afzal, Chattha, Navraj, Old, William, Pegg, Claire, Davey, Miriam, Page, Michelle, Sandhu, Banher, Phiri, Emily, Rashed, Khalid, Wilson, Elisabeth, Hindley, Esther, Board, Sarah, Antony, Sherly, Tanate, Alfonso, Davis, Michelle, Holland, Beth, Slater, Victoria, Fawcett, Michelle, England, Tim, Scott, James, Beavan, Jessica, Hedstrom, Amanda, Karunatilake, Dumin, Gillmain, Kimberley, Singh, Nishy, Hallows, Tracy, Barber, Mark, Yates, Luke, Micallef, Clayton, Esson, Derek, Meng Yu, Wai, Ming New, Benjamin Jaa, Matos, Alexandre, Burt, Clare, Cabrelli, Louise, Wilkie, Gillian, Meegada, Madana, Kirthivasan, Ramanathan, Fox, Caroline, Mead, Victoria, Lyle, Amanda, Saksena, Rajesh, Bakshi, Aashima, O'Kelly, Alison, Rehan, Jahanzeb, Ebueka, Osaretin, Cooper, Martin, Wynter, Inez, Smith, Susan, Kumar, Senthil, O'Brien, Linda, Parker, Cerrys, Parker, Emma, Khan, Numan, Patterson, Christopher, Maguire, Stuart, Quinn, Outi, Bellfield, Ruth, Behnam, Yousif, Costa, Janet, Padilla-Harris, Cheryl, Moram, Louise, Raza, Syed Abid, Tench, Helen, Sims, Tanya, McGuinness, Heather, Loosley, Ronda, Wolf-Roberts, Rebecca, Buddha, Sandeep, Salt, Irmak, Lewis, Kerry, Mavinamne, Sunanda, Ditchfield, Coleen, Dealing, Sharon, Shah, Alexander, Crossingham, Ginette, Mwadeyi, Memory, Kenton, Anthony, Omoregie, Faith, Abubakar, Saidu, Warwick, Allison, Hector, Gemma, Hassan, Ahamad, Veraque, Emelda, Farman, Michelle, Makawa, Linetty, Byrne, Anthony, Kirkham, Jackie, Blayney, Gareth, Selwyn, Jey, Kakar, Puneet, Al Khaddour, Mohammed, Dhami, Reena, Baker, Emelda, Esisi, Bernard, Clarkson, Emma, Fellowes, Dominic, Kresmir, Jergovic, Guyler, Paul, Ngo, David, Wijenayake, Indunil, Tysoe, Sharon, Galliford, Joanne, Harman, Paula, Garside, Mark, Badanahatti, Madhava, Riddell, Victoria, Gramizadeh, Gita, Dutta, Dipankar, Bajoriene, Milda, Erdogan, Hulya, Ward, Deborah, Doubal, Fergus, Samarasekera, Neshika, Risbridger, Sarah, MacRaild, Allan, Azim, Abul, Wood, Lisa, Tampset, Ruth, Shekhar, Raj, Rai, Umesh, Fuller, Tracy, Joshy, Aricsa, Nadar, Evelyn, 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Gadapa, Naveen, Choudhary, Sumita, Nisar, Nabeela, Fawehinmi, Grace, Dunne, Karen, King, Sam, Kishore, Amit, Lee, Stephanie, Marsden, Tracy, Slaughter, Melanie, Cawley, Kathryn, Perez, Jane, Anderton, Peter, Soussi, Salem, Walstow, Deborah, Pugh, Rebecca, Manoj, Aravind, Fletcher, Glynn, Lopez, Paula, McCormick, Michael, Magee, Michael, Tallon, Grainne, McFarland, Denise, Cosgrove, Denise, Shinh, Naval, Metcalf, Kneale, Kostyuk, Alina, McDonald, Susan, Sayers, Sophie, Sayed, Walee, Abraham, Sam, Szabo, Gemma, Crosbie, Gareth, McIlmoyle, Jim, Fearon, Patricia, Courtney, Kerry, Tauro, Suzanne, Singh, Arun, Nair, Anand, Duberley, Stephen, Philip, Sheeba, Curley, Cath, Goddard, Wendy, Bridge, Luke, Willcoxson, Paul, Wanklyn, Peter, Owen, Jennifer, France, John, Reed, Bryony, Foulds, Angie, Richard, Bella, Parfitt, Louise, Affley, Brendan, Russo, Cristina, Dsouza, Margaret, Cruddas, Elizabeth, Hargroves, David, Rand, James, Shekar, Som, Bhat, Yaqoob, Marshall, Gail, Nash, Maxine, Ahmad, Nasar, Okoko, Blessing Oduh, Evans, Rachel, Taylor, Tegan, Dawson, Jesse, Colquhoun, Elizabeth, James, Christopher, Aguirre, Carlos, MacPhee, Catherine, Phipps, Janet, Ispoglou, Sissi, Hayes, Anne, Werring, David J, Dehbi, Hakim-Moulay, Ahmed, Norin, Arram, Liz, Best, Jonathan G, Balogun, Maryam, Bennett, Kate, Bordea, Ekaterina, Caverly, Emilia, Chau, Marisa, Cohen, Hannah, Cullen, Mairead, Doré, Caroline J, Engelter, Stefan T, Fenner, Robert, Ford, Gary A, Gill, Aneet, Hunter, Rachael, James, Martin, Jayanthi, Archana, Lip, Gregory Y H, Massingham, Sue, Murray, Macey L, Mazurczak, Iwona, Nash, Philip S, Ndoutoumou, Amalia, Norrving, Bo, Sims, Hannah, Sprigg, Nikola, Vanniyasingam, Tishok, and Freemantle, Nick

Published
2024
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39. Risk assessment of cadmium exposure of Shanghai residents based on different dietary exposure assessment methods

Author

CAI Hua, LUO Baozhang, QIN Luxin, QIU Danping, YANG Jingjin, SONG Xia, XU Biyao, ZHU Zhenni, LIU Hong, and WU Chunfeng

Subjects
cadmium, dietary exposure, total diet study, food frequency questionnaire, risk assessment, Medicine
Abstract

ObjectiveTo conduct comprehensive assessment of internal and external cadmium exposure and health risks for Shanghai residents.MethodsCadmium levels in food samples were calculated by employing two dietary exposure assessment methods， total diet study （TDS） and food frequency questionnaire （FFQ）， to estimate the daily dietary cadmium exposure of Shanghai residents. The provisional tolerable monthly intake （PTMI） of cadmium set by joint food and agriculture organization/WHO expert committee on food additives （JECFA） was applied to evaluate the health risk. Differences in dietary and urinary cadmium were compared by rank-sum test among different regions， age， gender， smoking status， and BMI groups， and the association between internal and external cadmium exposure was investigated by correlation analysis.ResultsThe mean value of urinary cadmium for 1 300 respondents was 0.542 μg·L-1. Urinary cadmium was higher in the population in central urban and urban-rural fringe areas than in the suburban area， higher in the older age group than in the younger age group， and higher in the smoking group than in the non-smoking group （all P

Published
2024
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43. Novel and robust treatment of pulmonary hypertension with netrin-1 and netrin-1-derived small peptides

Author

Murugesan, Priya, Zhang, Yixuan, Youn, Ji Youn, and Cai, Hua

Subjects
Biochemistry and Cell Biology, Medicinal and Biomolecular Chemistry, Chemical Sciences, Biological Sciences, Cardiovascular, Lung, Heart Disease, 2.1 Biological and endogenous factors, Aetiology, Pulmonary hypertension, Netrin-1, Netrin-1 derived small peptides, Hypoxia, Mean pulmonary arterial pressure, Right ventricular systolic pressure, Right ventricular hypertrophy, Pulmonary vascular remodeling, Nitric oxide (NO) bioavailability, Superoxide production, Endothelial nitric oxide synthase (eNOS)&nbsp, uncoupling, Oxidative stress, Endothelial nitric oxide synthase (eNOS) uncoupling, Medical Biochemistry and Metabolomics, Pharmacology and Pharmaceutical Sciences, Biochemistry and cell biology, Medicinal and biomolecular chemistry
Abstract

Limited medical therapies have been implemented for the treatment of the devastating cardiorespiratory disease of pulmonary hypertension (PH) while none of which is sufficiently effective to stop or regress development of PH. We have previously shown that netrin-1, an axon-guiding protein during development, protects against ischemia reperfusion injury induced myocardial infarction via modest and stable production of nitric oxide (NO) and attenuation of oxidative stress. Since NO deficiency and oxidative stress-mediated vascular remodeling play important roles in the pathogenesis of PH, our present study investigated therapeutic effects on PH of netrin-1 and its derived small peptides. Infused into mice for 3 weeks during exposure to hypoxia, netrin-1 and netrin-1 derived small peptides V1, V2 or V3 substantially alleviated pathophysiological and molecular features of PH, as indicated by abrogated increases in mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP), attenuated right ventricular hypertrophy, diminished vascular remodeling of medial thickening and upregulation in smooth muscle alpha-actin (SMA) and proliferative cell nuclear antigen (PCNA), and alleviated perivascular and peribronchial fibrosis reflected by collagen deposition. NO bioavailability was substantially improved by treatment with netrin-1 and netrin-1 derived small peptides, while hypoxia induced increases in total superoxide production and eNOS uncoupling activity were all attenuated. These dual mechanisms of increasing NO bioavailability and decreasing oxidative stress at the same time, underlie robust protective effects on PH of netrin-1 and its derived small peptides, which are different from existing medications that primarily target NO signaling alone. Our data for the first time demonstrate intriguing findings that netrin-1 and netrin-1 derived small peptides can be used as novel and robust therapeutics for the treatment of PH.

Published
2022

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