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Chen Li,1,* Jun Hao,2,* Chuangshi Wang,2 Jie Yang,1 Yitian Zheng,1 Kuo Zhang,3 Wen Hui,4 Xiangbin Meng,1 Jun Gao,1 Wei Li,2 Yi-Da Tang1,5 1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, People’s Republic of China; 2Medical Research and Biometrics Center, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Science and Technology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Li; Yi-Da Tang, Email liwei@mrbc-nccd.com; tangyida@bjmu.edu.cnObjective: The incidence rate of thyroid diseases increased worldwide. This study aims to overview the changing landscape of drug clinical trials on thyroid disease during 2009– 2022.Methods: The detailed information of thyroid disease drug trials registered on the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform for Drug Clinical Studies was searched and collected. The thyroid drug clinical trials were analyzed by the characteristics, time trends, indications, and geographical distribution.Results: Sixty-five thyroid disease drug clinical trials were launched from 2009 to 2022 in China, which included 21 trials in nontumorous thyroid disease and 44 trials in thyroid carcinoma. The number of registered trials of thyroid diseases including thyroid carcinoma and nontumorous thyroid disease increased steadily from 2009 to 2020. Bioequivalence studies accounted for the largest proportion (32[49.2%]), while phase I and Phase II studies both only accounted for 18.5% (12/65). A significant difference was observed in the trials phase, and randomization between thyroid carcinoma and nontumorous thyroid disease. In terms of clinical indications and drug mechanisms, the number of trials in multi-target tyrosine kinase inhibitors for thyroid carcinoma (n=35) ranked first, followed by thyroid hormone for hypothyroidism (n=7), thyrotropin for thyroid carcinoma (n=6). Sixty-five trials were led by 36 principal investigator (PI) units, and more than 30% of PI-leading units were located in Shanghai (n=7) and Beijing (n=4).Conclusion: During the past 13 years, the development of thyroid diseases drugs trials has achieved certain progress in thyroid carcinoma, especially the molecular targeted therapy, yet the development of drug trials on nontumorous thyroid disease was very slow.Keywords: thyroid disease, thyroid carcinoma, nontumorous thyroid disease, China, drug clinical trial

Yitian Zheng,1– 3,* Yu Qi,1,* Samuel Seery,4,5 Jie Yang,2,3 Chen Li,2,3 Wenyao Wang,1 Jun Gao,1 Xiangbin Meng,1 Chunli Shao,1 Yi-Da Tang1 1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, People’s Republic of China; 2Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4School of Humanities and Social Sciences, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, People’s Republic of China; 5Faculty of Health and Medicine, Division of Health Research, Lancaster University, Lancaster, UK*These authors contributed equally to this workCorrespondence: Yi-Da Tang, Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, People’s Republic of China, Email tangyida@bjmu.edu.cnObjective: Anti-inflammatory therapies are reported to have additional benefits beyond lipid control for patients with cardiovascular disease. However, no study has focused on the relationship between inflammation status and long-term outcomes for chronic obstructive pulmonary disease (COPD) patients, after percutaneous coronary intervention (PCI).Methods: 277 COPD-PCI patients were divided into two groups according to hsCRP status upon admission. Major adverse cardiac events (MACE) in high hsCRP patients were compared to patients with low hsCRP. Restricted cubic spline (RCS) analysis was performed using MACE hazard ratios (HR) to investigate interrelations with hsCRP, as a continuous variable.Results: Patients in the high hsCRP group incurred more inflammation activation, in terms of higher white blood cell counts, neutrophil, lymphocytes, and had higher smoking rates, compared to those with lower hsCRPs. A significant increase in MACEs was observed in hsCRP high group, compared to the low hsCRP group (HR: 2.47, 95% CI: 1.22– 5.00; p = 0.012). RCS curves suggest that HRs rise beyond 1.0, after the 0.24 juncture for Lg HsCRP (base 10 logarithm with hsCRP), HR per SD: 1.19 (95% CI: 0.96– 1.48). Further subgroup analysis implies that elevated hsCRP is associated with a higher risk of MACEs across the sub-groups tested.Conclusion: HsCRP could be a useful indicator for COPD-CAD patient prognosis, after PCI. This is because hsCRP highlights inflammation activation. More multi-center research, designed for COPD-CAD patients should be conducted to more accurately determine the cut-off value for hsCRP.Keywords: HsCRP, chronic obstructive pulmonary disease, coronary artery disease, percutaneous coronary intervention, outcomes

Wen-Jing Zhu,1 Ying Yan,2 Jiu-Wei Zhang,1 Yan-Dong Tang,3 Bo Han4 1Abdominal Ultrasonic Department, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2Oncology Department, The First Hospital of Harbin, Harbin, Heilongjiang Province, People’s Republic of China; 3Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang Province, People’s Republic of China; 4Oncology Department, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of ChinaCorrespondence: Bo HanOncology Department, The First Affiliated Hospital of Harbin Medical University, 23 Post Street, Harbin 150001, Heilongjiang Province, People’s Republic of ChinaEmail hanbo1964@163.comAim: This study aimed to investigate the effect and mechanism of miR-26a-5p on proliferation and apoptosis of hepatocellular carcinoma (HCC) cells.Methods: RT-PCR was used to analyze the expression of miR-26a-5p in HCC cells and its targeted gene HMGA2 mRNA determined by biological information prediction. The rate of proliferation, invasion, apoptosis, and expression levels of related proteins of HCC cells overexpressing miR-26a-5p or those after knocking down HMGA2 expression were detected by MTT, invasion and apoptosis rate tests. Moreover, the apoptosis-promoting protein bax was upregulated and the anti-apoptosis-related protein Bcl-2 was downregulated.Results: RT-qPCR results showed that the level of miR-26a-5p was downregulated in HCC tissues and cells, and the expression of HMGA2 was upregulated; besides, the expression of miR-26a-5p and HMGA2 was negatively correlated; miR-26a-5p was correlated with tumor diameter, differentiation degree, TNM staging and lymph node metastasis. Cell tests confirmed that miR-26a-5p functioned in tumor suppression, including inhibiting cell proliferation and invasion in two hepatocellular carcinoma cell lines and promoting apoptosis. Bioinformatics prediction and subsequent experiments proved that HMGA2 was the direct target of miR-26a-5p; moreover, after knocking down HMGA2 expression in HCC cells, cell proliferation and invasion ability were significantly inhibited, and apoptosis rate increased significantly.Conclusion: miR-26a-5p can inhibit the proliferation and invasion of HCC cells and promote their apoptosis by directly targeting HMGA2. Abnormal decrease of miR-26a-5p and increase of its target HMGA2 are important factors that may participate in the occurrence and development of HCC. miR-26a-5p may be a new potential target for its treatment.Keywords: miR-26a-5p, hepatocellular carcinoma cells, proliferation, apoptosis, mechanism research

Xiangbin Meng,1,* Wenyao Wang,2,* Kuo Zhang,2,* Yu Qi,2 Shimin An,2 Siyuan Wang,2 Jilin Zheng,2 Joyce Kong,3 Henghui Liu,4 Jing Wu,4 Yong Zhou,5 Chuanyu Gao,1 Yi-Da Tang2 1Department of Cardiology, Zhengzhou University People’s Hospital, Zhengzhou, Henan, China; 2Department of Cardiology Medicine, Coronary Heart Disease Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 3New York Institute of Technology-College of Osteopathic Medicine, Old Westbury, NY, USA; 4Beijing Recdata Technology Co., Ltd., Beijing, China; 5Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vascular Diseases, Beijing, China *These authors contributed equally to this work Background: Epicardial adipose tissue (EAT) is considered an important source of bioactive molecules that can influence coronary arteries directly and is related to the concurrent presence of both obstructive coronary stenosis and myocardial ischemia independently. Non-alcoholic fatty liver disease (NAFLD) has become an emergent health problem worldwide. Aim: This cross-sectional study aimed to address the relationship between the volume of EAT and NAFLD and other cardiovascular risk factors in the general population. Materials and methods: In this study, we selected a total of 2,238 participants aged at least 40 years from the Jidong community in Tangshan, China. The 64-slice CT was used to survey the volume of EAT and liver ultrasonography was used for the diagnosis of NAFLD. The study cohorts were compared according to EAT volume. Results: Cardiovascular risk factors, such as coronary artery calcium score, carotid intima-media thickness, NAFLD, and ideal cardiovascular health metrics were also found to be related to EAT. In multivariate logistic regression analysis, NAFLD groups showed significant association with higher EAT volume, after correcting for main cardiovascular disease risk factors (OR [95% CI], 1.407 [1.117, 1.773]). Conclusion: Our findings in a general community population provide evidence that EAT is strongly associated with NAFLD and other cardiovascular risk factors. Keywords: epicardial adipose tissue, EAT, coronary artery calcium, CAC, carotid intima-media thickness, CIMT, ideal cardiovascular health metrics, CVH