Host metabolism dysregulation and cell tropism identification in human airway and alveolar organoids upon SARS-CoV-2 infection

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs. The infected cells were ciliated, club, and alveolar type 2 (AT2) cells, which were sequentially located from the proximal to the distal airway and terminal alveoli, respectively. Additionally, RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes, especially lipid metabolism, in addition to the well-known upregulation of immune response. Further, Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.

Influence of metoprolol tartrate combined Danhong injection on ECG and serum BNP and sICAM—1 lev— els in patients with UAP of CHD / 心血管康复医学杂志

Objective :To explore therapeutic effect of metoprolol tartrate combined Danhong injection on patients with unstable angina pectoris of coronary heart disease (CHD—UAP) and its influence on serum levels of brain natri—uretic peptide (BNP) and soluble intercellular adhesion molecule—1 (sICAM—1).Methods : A total of 104 CHD—UAP patients treated in our hospital from Mar 2013 to May 2017 were randomly and equally divided into metoprolol group (received metoprolol based on routine treatment ) and combined treatment group (received Danhong injection based on metoprolol group) ,both groups were continuously treated for two weeks .Onset frequency and duration of angina pectoris ,serum BNP and sICAM—1 levels before and two weeks after treatment ,and incidence of adverse reactions were observed and compared between two groups .Results : After two—week ,clinical total effective rate (84. 62%vs.63. 46%) and ECG total effective rate (90.38% vs.69. 23%) of combined treatment group were significantly higher than those of metoprolol group , P＝0. 014 ,0.007. Compared with before treatment ,there were significant reductions in onset frequency and duration of angina pectoris and serum levels of BNP and sICAM—1 after two—week treatment in two groups , P＝0.001 all ;compared with metoprolol group after two—week treatment ,there were sig—nificant reductions in onset frequency [ (6. 03 ± 0.72 ) times／week vs .(2.69 ± 0.54 ) times／week ] and duration [ (4. 82 ± 0.51) min／time vs .(2. 65 ± 0.70) min／time] of angina pectoris ,serum levels of BNP [ (652.43 ± 97. 15) pg／ml vs .(536. 27 ± 95. 40) pg／ml] and sICAM—1 [ (105.27 ± 29.14) ng／L vs.(81.03 ± 26. 43) ng／L] in combined treatment group , P＝0. 001 all.There was no significant difference in incidence rate of adverse reactions between two groups , P＝0.506. Conclusion : Metoprolol tartrate combined Danhong injection possesses significant therapeu—tic effect on CHD—UAP patients .It can effectively reduce serum BNP and sICAM—1 levels ,onset frequency and du—ration of angina pectoris with high safety ,which is worth extending .

Expression of Connective Tissue Growth Factor in Patients With ST-segment Elevation Myocardial Infarction / 中国循环杂志

Objective: To detect the changes of serum level of connective tissue growth factor (CTGF) in patients with ST-segment elevation myocardial infarction (STEMI) and to study the correlation between CTGF level and the maximal activity of creatine kinase-MB (CK-MB). Methods: Our research included 2 groups of patients: STEMI group and unstable angina (UA) group. All patients were treated in our hospital from 2013-07 to 2014-06,n=50 in each group. In STEMI group, the serum levels of CTGF were examined by ELISA at 24h, 2, 7, 14 days of onset, and in UA group, CTGF level was examined at 24h of onset. The CK-MB activity levels were measured in STEMI group at the same time points by immunosuppression method. Results: The serum level of CTGF in UA patients at 24 h of onset was (10.34 ± 2.00) ng/mL, and in STEMI patients were (16.76 ± 3.17) ng/mL at 24h, (29.87 ± 4.90) ng/mL at 2d, (45.02 ± 8.35) ng/mL at 7d and (31.61 ± 4.40) at 14d. The CTGF levels in STEMI group at different time points were all higher than UA group at 24h of onset,P<0.01. In STEMI group, the CTGF levels were increasing from 24h to 7d, then decreasing at 14d, allP<0.01. In STEMI group, the highest protein concentration of CTGF was positively related to the maximal activity of CK-MB at 7 days of onset (r=0.859,P=0.000). Conclusion: CTGF expression has been up-regulated in STEMI patients which might be related to myocardial ifbrosis. The protein level of CTGF is related to MI size, it shows certain predictive value in relevant patients.

Clinical Characteristics of Coronary Slow Flow in Relevant Patients / 中国循环杂志

Objective: To explore the clinical and anatomical characteristics of coronary slow lfow (CSF) in relevant patients. Methods: We summarized the patients without coronary angiography (CAG) proved coronary stenosis (stenosis 27 and Control group,n=55 patients with normal coronary lfow. The related laboratory indexes were examined and relationship between MCV and CSF was studied by multi-logistic regression analysis. Results: In CSF group, MCV 90.4 (87.48, 92.65) fL and RDW-CV 12.5 (12.30, 13.18) % were lower than those in Control group 92.3 (90.1, 94.3) fL and 13(12.7, 13.4) %,P Conclusion: Deformability of red blood cells might be involved in pathogenesis of CSF in relevant patients.