Proteomic profiling of epicardial fat in heart failure with preserved versus reduced and mildly reduced ejection fraction.

In order to explore the proteomic signatures of epicardial adipose tissue (EAT) related to the mechanism of heart failure with reduced and mildly reduced ejection fraction (HFrEF/HFmrEF) and heart failure (HF) with preserved ejection fraction (HFpEF), a comprehensive proteomic analysis of EAT was made in HFrEF/HFmrEF (n = 5) and HFpEF (n = 5) patients with liquid chromatography-tandem mass spectrometry experiments. The selected differential proteins were verified between HFrEF/HFmrEF (n = 20) and HFpEF (n = 40) by ELISA (enzyme-linked immunosorbent assay). A total of 599 EAT proteins were significantly different in expression between HFrEF/HFmrEF and HFpEF. Among the 599 proteins, 58 proteins increased in HFrEF/HFmrEF compared to HFpEF, whereas 541 proteins decreased in HFrEF/HFmrEF. Of these proteins, TGM2 in EAT was down-regulated in HFrEF/HFmrEF patients and was confirmed to decrease in circulating plasma of the HFrEF/HFmrEF group (p = 0.019). Multivariate logistic regression analysis confirmed plasma TGM2 could be an independent predictor of HFrEF/HFmrEF (p = 0.033). Receiver operating curve analysis indicated that the combination of TGM2 and Gensini score improved the diagnostic value of HFrEF/HFmrEF (p = 0.002). In summary, for the first time, we described the proteome in EAT in both HFpEF and HFrEF/HFmrEF and identified a comprehensive dimension of potential targets for the mechanism behind the EF spectrum. Exploring the role of EAT may offer potential targets for preventive intervention of HF.

Drug-induced liver injury following the use of tocilizumab or sarilumab in patients with coronavirus disease 2019.

BACKGROUNDS: Interleukin-6 (IL-6) blockers including tocilizumab and sarilumab were approved by the U.S. Food and Drug Administration (FDA) in June 2021 for the treatment of patients with moderate to severe COVID-19. The use of sarilumab or tocilizumab in COVID-19 patients has been related to a reduction in mortality compared to standard care. Recent evidence has emerged concerning drug-induced liver injury (DILI) after sarilumab or tocilizumab applications in COVID-19 patients. AIMS: The study aimed to estimate DILI associated with sarilumab or tocilizumab in treating moderate to severe patients infected with SARS-Cov-2. METHODS: We conducted a retrospective pharmacovigilance study by data mining of the FDA's adverse event reporting systems (FAERS) database from the first quarter of 2004 to the fourth quarter of 2021 in confirmed COVID-19 patients. We analyzed DILI cases associated with tocilizumab or sarilumab in treating COVID-19 patients from the FAERS during this period. Disproportionality analysis and Bayesian analysis of COVID-19 patients were utilized for case analysis, and we also next compared the onset time and fatality rates of DILI following tocilizumab or sarilumab. RESULTS: A total of 275 cases of TCZ or SAR-related DILI reports were extracted. A total of 192 AEs cases were related to tocilizumab (TCZ), and 83 were related to sarilumab (SAR). In patients treated with TCZ, most were < 75 years old (51.57%), with more male than female (46.35% vs. 13.02%). The correlation between IL-6 receptor antagonists and DILI was stronger in SAR (ROR = 12.94; 95%CI 9.6-17.44) than in TCZ (ROR = 1.33; 95%CI 1.14-1.55). The onset time of DILI was different between TCZ and SAR, and a significant difference was observed in TCZ than SAR (P < 0.0001). A significant difference was observed in the mortality rate of TCZ and SAR (P = 0.0009). DILI associated with COVID-19 patients treated with TCZ appeared to have earlier onset-time (1(0-46) day) VS. SAR (3.5(0-27) day). CONCLUSION: This study shows strict monitor ought to be paid for TCZ or SAR when used for COVID-19 patients with poor liver function.

Effect of Nucleic Acid Screening Measures on COVID-19 Transmission in Cities of Different Scales and Assessment of Related Testing Resource Demands-Evidence from China.

BACKGROUND: COVID-19 is in its epidemic period, and China is still facing the dual risks of import and domestic rebound. To better control the COVID-19 pandemic under the existing conditions, the focus of this study is to simulate the nucleic acid testing for different population size cities in China to influence the spread of COVID-19, assess the situation under different scenarios, the demand for the laboratory testing personnel, material resources, for the implementation of the nucleic acid screening measures, emergency supplies, and the configuration of human resources to provide decision-making basis. METHODS: According to the transmission characteristics of COVID-19 and the current prevention and control strategies in China, four epidemic scenarios were assumed. Based on the constructed SVEAIiQHR model, the number of people infected with COVID-19 in cities with populations of 10 million, 5 million, and 500,000 was analyzed and predicted under the four scenarios, and the demand for laboratory testing resources was evaluated, respectively. RESULTS: For large, medium, and small cities, whether full or regional nucleic acid screening can significantly reduce the epidemic prevention and control strategy of different scenarios laboratory testing resource demand difference is bigger, implement effective non-pharmaceutical interventions and regional nucleic acid screening measures to significantly reduce laboratory testing related resources demand, but will cause varying degrees of inspection staff shortages. CONCLUSION: There is still an urgent need for laboratory testing manpower in China to implement effective nucleic acid screening measures in the event of an outbreak. Cities or regions with different population sizes and levels of medical resources should flexibly implement prevention and control measures according to specific conditions after the outbreak, assess laboratory testing and human resource need as soon as possible, and prepare and allocate materials and personnel.

Assessment of the Effect on Thromboprophylaxis with Multifaceted Quality Improvement Intervention based on Clinical Decision Support System in Hospitalized Patients: A Pilot Study.

BACKGROUND: To explore the feasibility and effectiveness of multifaceted quality improvement intervention based on the clinical decision support system (CDSS) in VTE prophylaxis in hospitalized patients. METHODS: A randomized, department-based clinical trial was conducted in the department of respiratory and critical care medicine, orthopedic, and general surgery wards. Patients aged ≥18 years, without VTE in admission, were allocated to the intervention group and received regular care combined with multifaceted quality improvement intervention based on CDSS during hospitalization. VTE prophylaxis rate and the occurrence of hospital-associated VTE events were analyzed as primary and secondary outcomes. RESULTS: A total of 3644 eligible residents were enrolled in this trial. With the implementation of the multifaceted quality improvement intervention based on the CDSS, the VTE prophylaxis rate of the intervention group increased from 22.93% to 34.56% (p < 0.001), and the incidence of HA-VTE events increased from 0.49% to 1.00% (p = 0.366). In the nonintervention group, the VTE prophylaxis rate increased from 24.49% to 27.90% (p = 0.091), and the incidence of HA-VTE events increased from 0.47% to 2.02% (p = 0.001). CONCLUSIONS: Multifaceted quality improvement intervention based on the CDSS strategy is feasible and expected to facilitate implementation of the recommended VTE prophylaxis strategies and reduce the incidence of HA-VTE in hospital. However, it is necessary to conduct more multicenter clinical trials in the future to provide more reliable real-world evidence.

Real-time monitoring of isothermal nucleic acid amplification on a smartphone by using a portable electrochemical device for home-testing of SARS-CoV-2.

Home-testing of SARS-CoV-2 is an ideal approach for controlling the pandemic of COVID-19 and alleviating the shortage of medical resource caused by this acute infectious disease. Herein, a portable device that enables real-time monitoring of isothermal nucleic acid amplification tests (INAATs) through the electrochemistry method was fabricated for home-testing of SARS-CoV-2. First, a disposable plug-and-play pH-sensitive potentiometric sensor that matches this electrochemical INAATs (E-INAATs) device was designed to allow the label-free pH sensing detection of nucleic acid. By applying Nafion film on the polyaniline-based working electrode, this sensor exhibited an excellent linear potentiometric response to pH value in the range of 6.0-8.5 with a slope of -37.45 ± 1.96 mV/pH unit. A Bluetooth module was integrated into this device to enable the users real-time monitoring INAATs on their smartphones at home. Moreover, by presetting criteria, the detection results could be automatically judged by the device to avoid human errors. Finally, the utility of this E-INAATs device was demonstrated by detecting the presence of SARS-CoV-2 nucleocapsid protein gene in artificial samples with a sensitivity of 2 × 102 copies/test within 25 min, which was comparable with fluorescence and colorimetric assay. This portable, easy-operated, sensitive, and affordable device is particularly desirable for the full integration of household SARS-CoV-2 detection products and will open a new prospect for the control of infectious diseases via electrochemical NAATs.

Interrelationship between 2019-nCov receptor DPP4 and diabetes mellitus targets based on protein interaction network.

Patients with diabetes are more likely to be infected with Coronavirus disease 2019 (COVID-19), and the risk of death is significantly higher than ordinary patients. Dipeptidyl peptidase-4 (DPP4) is one of the functional receptor of human coronavirus. Exploring the relationship between diabetes mellitus targets and DPP4 is particularly important for the management of patients with diabetes and COVID-19. We intend to study the protein interaction through the protein interaction network in order to find a new clue for the management of patients with diabetes with COVID-19. Diabetes mellitus targets were obtained from GeneCards database. Targets with a relevance score exceeding 20 were included, and DPP4 protein was added manually. The initial protein interaction network was obtained through String. The targets directly related to DPP4 were selected as the final analysis targets. Importing them into String again to obtain the protein interaction network. Module identification, gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were carried out respectively. The impact of DPP4 on the whole network was analyzed by scoring the module where it located. 43 DPP4-related proteins were finally selected from the diabetes mellitus targets and three functional modules were found by the cluster analysis. Module 1 was involved in insulin secretion and glucagon signaling pathway, module 2 and module 3 were involved in signaling receptor binding. The scoring results showed that LEP and apoB in module 1 were the highest, and the scores of INS, IL6 and ALB of cross module associated proteins of module 1 were the highest. DPP4 is widely associated with key proteins in diabetes mellitus. COVID-19 may affect DPP4 in patients with diabetes mellitus, leading to high mortality of diabetes mellitus combined with COVID-19. DPP4 inhibitors and IL-6 antagonists can be considered to reduce the effect of COVID-19 infection on patients with diabetes.

Nomogram for prediction of fatal outcome in patients with severe COVID-19: a multicenter study.

BACKGROUND: To develop an effective model of predicting fatal outcomes in the severe coronavirus disease 2019 (COVID-19) patients. METHODS: Between February 20, 2020 and April 4, 2020, consecutive confirmed 2541 COVID-19 patients from three designated hospitals were enrolled in this study. All patients received chest computed tomography (CT) and serological examinations at admission. Laboratory tests included routine blood tests, liver function, renal function, coagulation profile, C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and arterial blood gas. The SaO2 was measured using pulse oxygen saturation in room air at resting status. Independent high-risk factors associated with death were analyzed using Cox proportional hazard model. A prognostic nomogram was constructed to predict the survival of severe COVID-19 patients. RESULTS: There were 124 severe patients in the training cohort, and there were 71 and 76 severe patients in the two independent validation cohorts, respectively. Multivariate Cox analysis indicated that age ≥ 70 years (HR = 1.184, 95% CI 1.061-1.321), panting (breathing rate ≥ 30/min) (HR = 3.300, 95% CI 2.509-6.286), lymphocyte count < 1.0 × 109/L (HR = 2.283, 95% CI 1.779-3.267), and interleukin-6 (IL-6) >  10 pg/ml (HR = 3.029, 95% CI 1.567-7.116) were independent high-risk factors associated with fatal outcome. We developed the nomogram for identifying survival of severe COVID-19 patients in the training cohort (AUC = 0.900, 95% CI 0.841-0.960, sensitivity 95.5%, specificity 77.5%); in validation cohort 1 (AUC = 0.811, 95% CI 0.763-0.961, sensitivity 77.3%, specificity 73.5%); in validation cohort 2 (AUC = 0.862, 95% CI 0.698-0.924, sensitivity 92.9%, specificity 64.5%). The calibration curve for probability of death indicated a good consistence between prediction by the nomogram and the actual observation. The prognosis of severe COVID-19 patients with high levels of IL-6 receiving tocilizumab were better than that of those patients without tocilizumab both in the training and validation cohorts, but without difference (P = 0.105 for training cohort, P = 0.133 for validation cohort 1, and P = 0.210 for validation cohort 2). CONCLUSIONS: This nomogram could help clinicians to identify severe patients who have high risk of death, and to develop more appropriate treatment strategies to reduce the mortality of severe patients. Tocilizumab may improve the prognosis of severe COVID-19 patients with high levels of IL-6.

Evaluating the Real-Time Impact of COVID-19 on Cities: China as a Case Study

Since the beginning of 2020, the COVID-19 epidemic has dramatically influenced the human socioeconomic system. If we conceive of the city as a complex organism with a metabolism, then the daily flows of people, materials, and information into and out of a city can be regarded as its metabolism. To evaluate the real-time impact of COVID-19 on a city’s economy and society, we construct a health index of cities (HIC) using human mobility big data from Baidu and analyze the temporal and spatial changes of the HIC in China. The results show that both internal and intercity population movements have been significantly affected by the COVID-19 epidemic, and the decline in both was more than 50% at some points. The intercity movement is more affected than the intracity movement, and the impact is more sustained. Compared with the same period before the outbreak, the HIC in China decreased by 28.6% from January 20 to April 21, 2020. The deterioration rate of the HIC was faster than the growth rate of COVID-19 cases, but the improvement in the HIC was much slower than the decline in COVID-19 cases. Although the HIC is highly correlated with COVID-19 in both the spatial and temporal dimensions, the effect of the epidemic on the HIC varied across regions. The HIC fell more significantly in provincial capitals, such as Beijing, Shanghai, Guangzhou, and Zhengzhou, and in urban agglomerations, and these cities’ HICs were lower with a longer-lasting reduction. This study can serve as a frame of reference for studying the real-time impact of the epidemic, helping cities’ policymakers to quickly assess its socioeconomic impact. By extension, this index can be applied to other countries and other public health emergencies.

Clinical Profile of COVID-19 in Children and Research Progress on Angiotensin-converting Enzyme 2: A Mini-review.

The cases of coronavirusdisease 2019 in children have been increasing with the ongoing pandemic.The finding suggests children have mild symptoms and a short course of the disease. Angiotensinconverting enzyme-2 mediates entry of the virus into the cell, the combination of virus and ACE2 leads to an increase in activity of angiotensin II, resulting in acute injury to lungs, myocardium and other organs. The infection causes down-regulation of ACE2 expression. The ACE2 plays an important role in the infection progression and clinical characteristics of COVID-19. Works on ACE2 and virus spike protein have future prospects of strategic information on prevention, management as well as vaccine development. Keywords: children;Coronavirus Disease 2019(COVID-19);SARS-Cov-2;angiotensin-Converting Enzyme 2 (ACE2).

Development and clinical application of a rapid SARS-CoV-2 antibody test strip: A multi-center assessment across China.

BACKGROUND: The ongoing coronavirus disease 19 (COVID-19) is posing a threat to the public health globally. Serological test for SARS-CoV-2 antibody can improve early diagnosis of COVID-19 and serves as a valuable supplement to RNA detection. METHOD: A SARS-CoV-2 IgG/IgM combined antibody test strip based on colloidal gold immunochromatography assay was developed, with both spike protein and nucleocapsid protein of SARS-CoV-2 antigen used for antibody detection. From 3 medical institutions across China, serum or plasma of 170 patients with confirmed COVID-19 diagnosis and 300 normal controls were collected and tested with the strip. Sensitivity, specificity, kappa coefficient, receiver operating characteristic (ROC) curve, and area under the curve (AUC) were analyzed. Positive rates in different medical centers, age group, gender, and different disease course were compared. RESULTS: 158 out 170 samples from confirmed COVID-19 patients had positive results from the test, and 296 out of 300 samples from normal controls had negative results. The kit was 92.9% sensitive and 98.7% specific. The positive rate was 77.3% during the first week after disease onset, but reached 100% since day 9. AUC and kappa coefficient were 0.958 and 0.926, respectively, which showed the consistency of the test results with the standard diagnosis. Age or gender caused little variations in the kit sensitivity. CONCLUSION: The rapid, easy-to-use SARS-CoV-2 IgG/IgM combined antibody test kit has a superior performance, which can help with accurate diagnosis and thus timely treatment and isolation of COVID-19 patients, that contributes to the better control of the global pandemic.