Implementation and Application of Large-Scale Drug Virtual Screening

The molecular docking-based virtual screening technique evaluates the binding abilities between multiple ligand compounds and receptors to screen for the active compounds. In the context of the global spread of the COVID-19 pandemic, large-scale and rapid drug virtual screening is crucial for identifying potential drug molecules from massive datasets of ligand structures. The powerful computing power of supercomputer provides hardware guarantee for drug virtual screening, but the super large-scale drug virtual screening still faces many challenges that affects the effective execution of the calculation. Based on the analysis of the challenges, this paper proposes a centralized task distribution scheme with a central database, and designs a multi-level task distribution framework. The challenges are effectively solved through multi-level intelligent scheduling, multi-level compression processing of massive small molecule files, dynamic load balancing and high error tolerance management technology. An easy-touse"tree”multi-level task distribution system is implemented. A fast, efficient and stable drug virtual screening task distribution, calculation and result analysis function is realized, and the computing efficiency is nearly linear. Then, heterogeneous computing technology is used to complete the drug virtual screening of more than 2 billion compounds, for two different active sites for COVID-19, on the domestic super computing system, which provides a powerful computing guarantee for the super large-scale rapid virtual screening of explosive malignant infectious diseases. © 2023, Journal of Computer Engineering and Applications Beijing Co., Ltd.;Science Press. All rights reserved.

Thoughts on diagnosis and treatment plan of patients infected with severe acute respiratory syndrome coronavirus 2 omicron variant in large shelter hospitals in Shanghai.

The epidemic caused by the infection of severe acute respiratory syndrome coronavirus 2 omicron variant broke out in Shanghai in Mar. 2022. Omicron variant has characteristics such as strong concealment and rapid transmission, resulting in significant differences between the current round of epidemic and that in Wuhan. The number of infected patients (mainly asymptomatic infected patients) increased rapidly in a short term. Based on dynamic zero policy, shelter hospitals were set up in time in Shanghai to treat the patients. It is suggested that medical resources and patient characteristics should be taken into account in the independent cabin of a shelter hospital with more than 10 000 beds, and the clinical medical practice should be divided to 5 modes (universal education and management, community outpatient clinic, ward duty, emergency rescue, and temporary observation and transport) to optimize the allocation of medical resources, so as to further enhance the treatment capacity and efficiency of shelter hospitals.Copyright © 2022, Second Military Medical University Press. All rights reserved.

Mental health status of military healthcare workers in shelter hospitals in Shanghai during the epidemic caused by severe acute respiratory syndrome coronavirus 2 omicron variant and its influencing factors.

Objective To investigate the mental health status of military healthcare workers in shelter hospitals in Shanghai during the epidemic caused by severe acute respiratory syndrome coronavirus 2 omicron variant and its influencing factors. Methods A total of 540 military healthcare workers in shelter hospitals in Shanghai were investigated with patient health questionnaire-9 (PHQ-9), generalized anxiety disorder-7 (GAD-7) and Athens insomnia scale (AIS) to explore their mental health status, and logistic regression was used to analyze the influencing factors. Results A total of 536 valid questionnaires were collected, with an effective rate of 99.3% (536/540). The incidence of depression, anxiety and insomnia among military healthcare workers in shelter hospitals in Shanghai was 45.5% (244/536), 26.1% (140/536) and 59.5% (319/536), respectively. Logistic regression analysis showed that whether people resided in Shanghai, the proportion of negative information in daily browsing information and diet status in shelter hospitals were the influencing factors of depression, anxiety and insomnia (all P<0.05);age and confidence in the future of Shanghai were the influencing factors of depression and insomnia (all P<0.05);and the time spent daily on epidemic-related information was an influencing factor of insomnia (P=0.021). Conclusion The incidence of depressive, anxiety and insomnia among military healthcare workers in shelter hospitals in Shanghai is high during the epidemic caused by severe acute respiratory syndrome coronavirus 2 omicron variant. Psychological consequences of the epidemic should be monitored regularly and continuously to promote the mental health of military healthcare workers.Copyright © 2022, Second Military Medical University Press. All rights reserved.

Modern pandemic crises and R&D investment

This study investigates the impact of crises caused by pandemics on firms' R&D investments. We explore these associations by utilizing a comprehensive cross-country sample of 261,959 firm-year observations collected from 39 countries during five modern health crises (SARS in 2003, H1N1 in 2009, MERS in 2012, Ebola in 2012, and Zika in 2016). The results indicate that pandemics have a positive and significant impact on R&D investment. Furthermore, we show that private firms in civil-law countries were more likely to adopt conservative financial policies than those in common-law countries. We conclude that the difference between the legal origins of private firms influences the impact on R&D investment. Moreover, it promotes conservative policies to reduce private firms' R&D investment in countries with civil law.

Mental health status of military healthcare workers in shelter hospitals in Shanghai during the epidemic caused by severe acute respiratory syndrome coronavirus 2 omicron variant and its influencing factors

Objective To investigate the mental health status of military healthcare workers in shelter hospitals in Shanghai during the epidemic caused by severe acute respiratory syndrome coronavirus 2 omicron variant and its influencing factors. Methods A total of 540 military healthcare workers in shelter hospitals in Shanghai were investigated with patient health questionnaire-9 (PHQ-9), generalized anxiety disorder-7 (GAD-7) and Athens insomnia scale (AIS) to explore their mental health status, and logistic regression was used to analyze the influencing factors. Results A total of 536 valid questionnaires were collected, with an effective rate of 99.3% (536/540). The incidence of depression, anxiety and insomnia among military healthcare workers in shelter hospitals in Shanghai was 45.5% (244/536), 26.1% (140/536) and 59.5% (319/536), respectively. Logistic regression analysis showed that whether people resided in Shanghai, the proportion of negative information in daily browsing information and diet status in shelter hospitals were the influencing factors of depression, anxiety and insomnia (all P<0.05);age and confidence in the future of Shanghai were the influencing factors of depression and insomnia (all P<0.05);and the time spent daily on epidemic-related information was an influencing factor of insomnia (P=0.021). Conclusion The incidence of depressive, anxiety and insomnia among military healthcare workers in shelter hospitals in Shanghai is high during the epidemic caused by severe acute respiratory syndrome coronavirus 2 omicron variant. Psychological consequences of the epidemic should be monitored regularly and continuously to promote the mental health of military healthcare workers.Copyright © 2022, Second Military Medical University Press. All rights reserved.

Thoughts on diagnosis and treatment plan of patients infected with severe acute respiratory syndrome coronavirus 2 omicron variant in large shelter hospitals in Shanghai

The epidemic caused by the infection of severe acute respiratory syndrome coronavirus 2 omicron variant broke out in Shanghai in Mar. 2022. Omicron variant has characteristics such as strong concealment and rapid transmission, resulting in significant differences between the current round of epidemic and that in Wuhan. The number of infected patients (mainly asymptomatic infected patients) increased rapidly in a short term. Based on dynamic zero policy, shelter hospitals were set up in time in Shanghai to treat the patients. It is suggested that medical resources and patient characteristics should be taken into account in the independent cabin of a shelter hospital with more than 10 000 beds, and the clinical medical practice should be divided to 5 modes (universal education and management, community outpatient clinic, ward duty, emergency rescue, and temporary observation and transport) to optimize the allocation of medical resources, so as to further enhance the treatment capacity and efficiency of shelter hospitals.Copyright © 2022, Second Military Medical University Press. All rights reserved.

[Comments on the systemic corticosteroid strategy for the coronavirus disease 2019 (COVID-19)].

Systemic corticosteroid is considered effective in treating severe or critical coronavirus disease 2019 (COVID-19) patients in both Chinese and international consensus and/or guidelines. Dexamethasone (6 mg daily for up to 10 days) is usually recommended. However, based on the outcomes of variable clinical trials and our clinical experience in treating the COVID-19 patients, the starting time, initial dosage and course of corticosteroid might be varied case by case. Individualized administration of corticosteroid is suggested according to the COVID-19 patient's demographic characteristics, underlying disease and immune status, severity and progression rate of COVID-19, inflammatory condition and concomitant use of non-steroidal anti-inflammatory drugs.

Restoration of Humoral Response to Covid-19 Vaccination in Rituximab-Treated Patients

Background: Previous studies had demonstrated that patients with hematologic malignancies had suboptimal antibody response after receiving COVID-19 vaccines, especially among those having previously treated with anti- CD20 monoclonal antibodies. Method(s): Adult patients with non-Hodgkin's lymphoma or chronic lymphocytic leukemia (CLL) were enrolled before receiving the second dose of SARS-CoV-2 vaccine. Determinations of anti-SARS-CoV-2 spike and nucleocapsid IgG titers were performed every 1-3 months, after they received the second and the third dose of SARS-CoV-2 vaccine, respectively. Patients were excluded from analysis if they were diagnosed with COVID-19. All serum samples were tested for anti-nucleocapsid antibody and those tested positive were excluded from subsequent analyses. Result(s): A total of 85 participants were enrolled, including 42 (49.4%) with diffused large B-cell lymphoma, and 13 (15.3) with follicular lymphoma and 9 with CLL. 72 (84.7%) participants had received anti-CD20 monoclonal antibodies, with a median interval of 24 months between last anti-CD20 treatment and the second dose of vaccine, and 21 (24.7%) had HIV infection. Factors associated with failure to achieve an anti-spike IgG titer >141 BAU/ mL within 12 weeks after the second dose of vaccine included HIV infection (adjusted odds ratio [aOR], 0.14;95% CI, 0.04-0.51), active hematologic disease (aOR, 5.50;95% CI 1.42-21.32), receipt of anti-CD20 monoclonal antibodies (aOR, 6.65;95% CI 1.52-29.07), and receipt of two doses of homologous mRNA vaccination (aOR, 0.17;95% CI 0.05-0.56). In the participants having previously treated with anti-CD20 regimen, only 8.6% achieved an antibody response ( >141 BAU/mL) in the first year, while 78.3% achieved anti-spike IgG titer > 141 BAU/mL after two years post B-cell depleting treatment. After the third dose of SARS-CoV-2 vaccine, 53.6% achieved an antispike IgG titer > 141 BAU/mL in the first year post anti-CD20 treatment. Conclusion(s): Our study demonstrated that previous treatment with anti-CD20 monoclonal antibodies was associated a lower antibody response among patients with lymphoproliferative disorders receiving two doses of SARS-CoV-2 vaccine. While two doses of SARS-CoV-2 vaccines might not be sufficient even one year apart from the last dose of rituximab, a third dose of vaccine may boost anti-spike IgG particularly in the subset of recent exposure to rituximab. Anti-spike IgG determined 1-3 months after the second (A) / third (B) dose of COVID-19 vaccine, stratified by the interval between last anti-CD20 regimen and the second / third dose of COVID-19 vaccine. (Figure Presented).

Potential Mechanism of Colchicine against COVID-19 and Non-Small Cell Lung Cancer based on Network Pharmacology and Bioinformatics Analysis

Colchicine is an alkaloid with antitumor effect isolated from Colchicum autumnale plants, it has been reported in multiple studies as a potential treatment for coronavirus disease-19 and this study applied network pharmacology and bioinformatics analysis to explore the potential mechanism of colchicine against non-small cell lung cancer and coronavirus disease-19. The R software was used to determine the differentially expressed genes of non-small cell lung cancer/coronavirus disease-19, and carry out prognostic analysis and clinical analysis of the differentially expressed genes, the targets of colchicine were obtained from various databases, the protein-protein interaction network of intersection targets of colchicine and non-small cell lung cancer/coronavirus disease-19 was constructed, enrichment analysis of gene ontology and kyoto encyclopedia of genes and genomes pathways was performed by Metascape database and the molecular docking and molecular dynamics simulation were completed. We obtained a total of 716 differentially expressed genes and identified 13 potential prognostic genes associated with the clinical characterization of non-small cell lung cancer/coronavirus disease-19 patients. C-C motif chemokine ligand 2, toll like receptor 4, intercellular adhesion molecule 1, peroxisome proliferator activated receptor gamma, interleukin 17A, interferon gamma, angiotensin I converting enzyme, fos proto-oncogene, nuclear factor kappa B inhibitor alpha, TIMP metallopeptidase inhibitor 1 and secreted phosphoprotein 1 were core targets. The intersection targets of colchicine and non-small cell lung cancer/coronavirus disease-19 were mainly enriched in biological processes such as inflammatory response, response to cytokine and response to lipopolysaccharide, as well as signal pathways such as interleukin 17 signaling pathway, hypoxia inducible factor 1 signaling pathway and nucleotide binding oligomerization domain-like receptor signaling pathway. The results of molecular docking showed that the colchicine is better combined with the core targets. Analysis of molecular dynamics simulation showed that the protein and ligand form a stabilizing effect. Based on bioinformatics analysis and network pharmacology, we obtained biomarkers that may be used for the prognosis of non-small cell lung cancer/coronavirus disease-19 patients and revealed that colchicine may play a potential role in the treatment of non-small cell lung cancer/coronavirus disease-19 by regulating multiple targets and multiple signaling pathways and participating in multiple biological processes.

Network analysis of sleep quality and anxiety of first-line medical staff in epidemic prevention

Objective: To explore the network characteristics of sleep quality and anxiety in first-line medical staff fighting against COVID-19, further understand the relationship between sleep quality and anxiety, and provide basis for intervention. Methods: Using the convenient sampling method, this paper used the Pittsburgh Sleep Quality Index (PSQI) and Self Rating Anxiety Scale (SAS) to conduct a questionnaire survey on the front-line medical staff who fought against the epidemic during the CO VID-19. Network analysis was used to construct sleep quality and anxiety network, and R language was used for statistical analysis and visualization. Results ：In the network of sleep quality and anxiety of first-line medical staff fighting against COVID-19 ?”sleep disorder"and usleep quality”, uunfortunate premonition"and uinability to sit still”, "syncope" and "hand and foot tingling"were highly related. "Fatigue”, "dizziness" and "panic” had the highest expected influence. "Sleep quality", "sleep disorder" and "fatigue"had the highest bridge expected influence. The average predictability value of all nodes was 0.778. Conclusion: This paper used network analysis to explore the sleep quality and anxiety of first-line medical staff fighting against COVID-19 and found that there was a unique correlation path between them. Intervention against core symptoms can ameliorate anxiety and sleep problems to the great extent, and provide guidance for improving the physical and mental health. © 2023, Editorial department of Chinese Medical Ethics. All rights reserved.

The Gift of Ancient Times: a Breakthrough in The Tracing of Modern Human Genes

The 2022 Nobel Prize in Physiology or Medicine was awarded to Swedish biologist Svante Pääbo for his decisive contribution to paleoanthropogenomics and human origins. There are various theories about the origin of human beings, and the current mainstream view is: out of the African doctrine. In other words, ancient humans had about three times of migrations. The first time was Homo erectus, the second was Neanderthals and Denisovans, and the third was the ancestors of modern humans. All migrated from Africa to Eurasia. While pioneering a new discipline, paleoanthropogenomics, Svante Pääbo has been refining the "Out of Africa Theory”. With the help of various biological techniques, he delved into the origin of human beings from the perspective of genomics and found that some genetic imprints from ancient humans were retained in our bodies. For example, the STAT2 gene and TLR gene associated with immunity, the EPAS1 gene that contributes to hypoxic respiration and the six genes of chromosome 3 are highly positively correlated with the incidence of COVID-19. This research means that we can go back to the root of certain diseases, rather than limiting our eyes to the genes themselves, and exploring where a gene comes from will be a new way of studying diseases. We summarized his innovations in related biotechnology in the process of research, his exploration of ancient humans based on mitochondrial and nuclear genes and related results, and introduced some genes derived from ancient humans and their related information. © 2022 Institute of Biophysics,Chinese Academy of Sciences. All rights reserved.

Challenges for volatility forecasts of US fossil energy spot markets during the COVID-19 crisis

The outbreak of the COVID-19 pandemic led to a slowdown in the world's energy trade and changes in the use of energy resources. Meanwhile, global conditions are complex and can affect fossil energy spot markets, including crude oil, gasoline, heating oil, and natural gas. In this paper, we conduct comparative research to explore the impact of global conditions on fossil energy spot markets during the COVID-19 crisis based on the GARCH-MIDAS framework. We employ a 2010–2022 sample, which we cut off to investigate the differences before and after COVID-19. In-sample estimation shows that all global indicators are significant for forecasting the volatilities of these fossil energy spot prices. Out-sample forecasts reveal that GEPU and GECON outperform GPR and WIP for forecasting these four markets during the pre-COVID-19 period. After the crisis broke out, these global indicators can provide different forecasting information. Hence, this paper can be helpful for decision-makers to formulate and adjust pertinent policies and investments in the case of extreme emergencies in the future. © 2023

Randomized controlled study protocol: Shensong Yangxin in persistent atrial fibrillation after radiofrequency catheter ablation (SS-ADJUST)

Introduction: Atrial fibrillation (AF) is one of the most common forms of arrhythmia in the clinic. There are about 10 million AF patients in China, of which 1/3 are paroxysmal AF, and the remaining 2/3 are persistent or permanent AF. Long-term AF impairs cardiac function and leads to heart failure and thromboembolism. Moreover, AF increases the risk of mortality and ischemic stroke. Drug therapy and radiofrequency catheter ablation (RFCA) are still the mainstream treatment for AF patients. However, drug therapy has its drawbacks because of the high recurrence rate and side effects. Therefore, the current antiarrhythmic drugs could not meet all the clinical needs of patients with AF. RFCA is superior to antiarrhythmic drugs in maintaining sinus rhythm, improving symptoms and exercise tolerance, and improving quality of life. The role of RFCA in the treatment of persistent AF has gradually been recognized and affirmed. Although RFCA has been progressively used in the treatment of AF, there is still a high recurrence rate of AF after RFCA, especially in patients with persistent AF. Hence, it is meant to solve the high recurrence rate of AF after RFCA. Shensong Yangxin (SSYX) capsule has been proven to treat arrhythmia both in animal studies and clinical research. SSYX capsule could regulate multi-ion channels, improve cardiomyocyte metabolism and regulate autonomic nervous function. In addition, randomized, double-blind, multicenter clinical research indicated that the SSYX capsule exhibited good clinical efficacy in treating ventricular premature beats and paroxysmal AF. However, the effect of SSYX on recurrence after RFCA for patients with persistent AF remains unclear. High-level randomized controlled trials (RCTs) could offer clinicians high-quality evidence regarding the usage of SSYX capsule, especially in persistent AF patients who received RFCA. Hence, the RCTs aim to evaluate the effect of SSYX capsules on the prognosis in patients with persistent AF after RFCA through multicenter, double-blind RCTs. Method(s): This trial will be conducted with a total of 920 participants diagnosed with persistent AF who received RFCA. The participants will be randomized (1:1) into groups receiving either SSYX or Placebo for 1 year. The primary endpoint includes the recurrence of AF within 1 year after RFCA. The secondary outcome measures include changes of AF load at 3 months, 6 months, 9 months, and 1 year after treatment, the time of first atrial flutter/AF, the incidence of cardioversion 1 year after treatment, changes of transthoracic echocardiographic parameters 1 year after treatment, the incidence of stroke and thromboembolism at 6 months and 1 year after treatment, the score of SF-36 within 1 year after treatment. Application: The trial is ongoing. The trial started in September 2019 and recruiting patients. Data collection will be completed after all participants have completed the treatment course and follow-up assessments (expected in 2022, pending COVID-19). Next Steps/Future: The SS-ADJUST study is a randomized control study of TCM in persistent AF after RFCA. It will determine the place of SSYX capsule as a new treatment approach and provide additional and innovative information regarding TCM and the specific use of SSYX in persistent AF after RFCA.

Graggle: A Graph-based Approach to Document Clustering

Document recommendation systems have traditionally relied upon high-dimensional vector representations that scale poorly in corpora with diverse vocabularies. Existing graph-based approaches focus on the metadata of documents and, unfortunately, ignore the content of the papers. In this work, we have designed and implemented a new system we call Graggle, which builds a graph to model a corpus. Nodes are papers, and edges represent significant words shared between them. We then leverage modern graph learning techniques to turn this graph into a highly efficient tool for dimensionality reduction. Documents are represented as low-dimensional vector embeddings generated with a graph autoencoder. Our experiments show that this approach outperforms traditional document vector-based and text autoencoding approaches on labeled data. Additionally, we have applied this technique to a repository of unlabeled research documents about the novel coronavirus to demonstrate its effectiveness as a real-world tool. © 2022 IEEE.

Network analysis of sleep quality and anxiety of first-line medical staff in epidemic prevention

Objective: To explore the network characteristics of sleep quality and anxiety in first-line medical staff fighting against COVID-19, further understand the relationship between sleep quality and anxiety, and provide basis for intervention. Methods: Using the convenient sampling method, this paper used the Pittsburgh Sleep Quality Index (PSQI) and Self Rating Anxiety Scale (SAS) to conduct a questionnaire survey on the front-line medical staff who fought against the epidemic during the CO VID-19. Network analysis was used to construct sleep quality and anxiety network, and R language was used for statistical analysis and visualization. Results ：In the network of sleep quality and anxiety of first-line medical staff fighting against COVID-19 ?”sleep disorder"and usleep quality”, uunfortunate premonition"and uinability to sit still”, "syncope" and "hand and foot tingling"were highly related. "Fatigue”, "dizziness" and "panic” had the highest expected influence. "Sleep quality", "sleep disorder" and "fatigue"had the highest bridge expected influence. The average predictability value of all nodes was 0.778. Conclusion: This paper used network analysis to explore the sleep quality and anxiety of first-line medical staff fighting against COVID-19 and found that there was a unique correlation path between them. Intervention against core symptoms can ameliorate anxiety and sleep problems to the great extent, and provide guidance for improving the physical and mental health. © 2023, Editorial department of Chinese Medical Ethics. All rights reserved.