Effect of EIT-guided PEEP titration on prognosis of patients with moderate to severe ARDS: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Acute respiratory syndrome distress (ARDS) is a clinical common syndrome with high mortality. Electrical impedance tomography (EIT)-guided positive end-expiratory pressure (PEEP) titration can achieve the compromise between lung overdistension and collapse which may minimize ventilator-induced lung injury in these patients. However, the effect of EIT-guided PEEP titration on the clinical outcomes remains unknown. The objective of this trial is to investigate the effects of EIT-guided PEEP titration on the clinical outcomes for moderate or severe ARDS, compared to the low fraction of inspired oxygen (FiO2)-PEEP table. METHODS: This is a prospective, multicenter, single-blind, parallel-group, adaptive designed, randomized controlled trial (RCT) with intention-to-treat analysis. Adult patients with moderate to severe ARDS less than 72 h after diagnosis will be included in this study. Participants in the intervention group will receive PEEP titrated by EIT with a stepwise decrease PEEP trial, whereas participants in the control group will select PEEP based on the low FiO2-PEEP table. Other ventilator parameters will be set according to the ARDSNet strategy. Participants will be followed up until 28 days after enrollment. Three hundred seventy-six participants will be recruited based on a 15% decrease of 28-day mortality in the intervention group, with an interim analysis for sample size re-estimation and futility assessment being undertaken once 188 participants have been recruited. The primary outcome is 28-day mortality. The secondary outcomes include ventilator-free days and shock-free days at day 28, length of ICU and hospital stay, the rate of successful weaning, proportion requiring rescue therapies, compilations, respiratory variables, and Sequential Organ Failure Assessment (SOFA). DISCUSSION: As a heterogeneous syndrome, ARDS has different responses to treatment and further results in different clinical outcomes. PEEP selection will depend on the properties of patients and can be individually achieved by EIT. This study will be the largest randomized trial to investigate thoroughly the effect of individual PEEP titrated by EIT in moderate to severe ARDS patients to date. TRIAL REGISTRATION: ClinicalTrial.gov NCT05207202. First published on January 26, 2022.

SARS-COV-2 spike protein promotes RPE cell senescence via the ROS/P53/P21 pathway.

SARS-Cov-2 infection, which has caused the COVID-19 global pandemic, triggers cellular senescence. In this study, we investigate the role of the SARS-COV-2 spike protein (S-protein) in regulating the senescence of RPE cells. The results showed that administration or overexpression of S-protein in ARPE-19 decreased cell proliferation with cell cycle arrest at the G1 phase. S-protein increased SA-ß-Gal positive ARPE-19 cells with high expression of P53 and P21, senescence-associated inflammatory factors (e.g., IL-1ß, IL-6, IL-8, ICAM, and VEGF), and ROS. Elimination of ROS by N-acetyl cysteine (NAC) or knocking down p21 by siRNA diminished S-protein-induced ARPE cell senescence. Both administrated and overexpressed S-protein colocalize with the ER and upregulate ER-stress-associated BIP, CHOP, ATF3, and ATF6 expression. S-protein induced P65 protein nuclear translocation. Inhibition of NF-κB by bay-11-7082 reduced S-protein-mediated expression of senescence-associated factors. Moreover, the intravitreal injection of S-protein upregulates senescence-associated inflammatory factors in the zebrafish retina. In conclusions, the S-protein of SARS-Cov-2 induces cellular senescence of ARPE-19 cells in vitro and the expression of senescence-associated cytokines in zebrafish retina in vivo likely by activating ER stress, ROS, and NF-κb. These results may uncover a potential association between SARS-cov-2 infection and development of AMD.

Whole genome DNA and RNA sequencing of whole blood elucidates the genetic architecture of gene expression underlying a wide range of diseases.

To create a scientific resource of expression quantitative trail loci (eQTL), we conducted a genome-wide association study (GWAS) using genotypes obtained from whole genome sequencing (WGS) of DNA and gene expression levels from RNA sequencing (RNA-seq) of whole blood in 2622 participants in Framingham Heart Study. We identified 6,778,286 cis-eQTL variant-gene transcript (eGene) pairs at p < 5 × 10-8 (2,855,111 unique cis-eQTL variants and 15,982 unique eGenes) and 1,469,754 trans-eQTL variant-eGene pairs at p < 1e-12 (526,056 unique trans-eQTL variants and 7233 unique eGenes). In addition, 442,379 cis-eQTL variants were associated with expression of 1518 long non-protein coding RNAs (lncRNAs). Gene Ontology (GO) analyses revealed that the top GO terms for cis-eGenes are enriched for immune functions (FDR < 0.05). The cis-eQTL variants are enriched for SNPs reported to be associated with 815 traits in prior GWAS, including cardiovascular disease risk factors. As proof of concept, we used this eQTL resource in conjunction with genetic variants from public GWAS databases in causal inference testing (e.g., COVID-19 severity). After Bonferroni correction, Mendelian randomization analyses identified putative causal associations of 60 eGenes with systolic blood pressure, 13 genes with coronary artery disease, and seven genes with COVID-19 severity. This study created a comprehensive eQTL resource via BioData Catalyst that will be made available to the scientific community. This will advance understanding of the genetic architecture of gene expression underlying a wide range of diseases.

COVID-19 and systemic lupus erythematosus genetics: A balance between autoimmune disease risk and protection against infection.

Genome wide association studies show there is a genetic component to severe COVID-19. We find evidence that the genome-wide genetic association signal with severe COVID-19 is correlated with that of systemic lupus erythematosus (SLE), having formally tested this using genetic correlation analysis by LD score regression. To identify the shared associated loci and gain insight into the shared genetic effects, using summary level data we performed meta-analyses, a local genetic correlation analysis and fine-mapping using stepwise regression and functional annotation. This identified multiple loci shared between the two traits, some of which exert opposing effects. The locus with most evidence of shared association is TYK2, a gene critical to the type I interferon pathway, where the local genetic correlation is negative. Another shared locus is CLEC1A, where the direction of effects is aligned, that encodes a lectin involved in cell signaling, and the anti-fungal immune response. Our analyses suggest that several loci with reciprocal effects between the two traits have a role in the defense response pathway, adding to the evidence that SLE risk alleles are protective against infection.

The influence mechanism of psychological contract on primary medical staff's turnover intention in the context of COVID-19 pandemic in China.

OBJECTIVE: This research aims to study the influence mechanism of psychological contract on the turnover intention of primary medical staff in the context of Corona Virus Disease 2019 (COVID-19) fighting. METHODS: Six hundred and fifteen primary medical staff from 13 primary health care institutions in Jianghan District, Wuhan City, Hubei Province, China were selected by random sampling. Psychological contract, emotional exhaustion and turnover intention questionnaires were adjusted appropriately according to research needs, and 5-point Likert scale was used to measure. RESULTS: Normal, interpersonal, and developmental contracts were negatively associated with turnover intention. Emotional exhaustion mediated the effects of interpersonal and developmental contracts on turnover intention. CONCLUSION: The government should establish a long-term incentive mechanism for primary medical staff, fully recognise the work of them in fighting against COVID-19, pay close attention to the psychological state of them, and carry out timely and effective psychological intervention to alleviate their emotional exhaustion and reduce their turnover intention.

Prevention and control mechanism for coronavirus disease 2019 epidemic at the primary level: perspective from China.

After the 2003 SARS epidemic, China started constructing a primary-level emergency response system and focused on strengthening and implementation of policies, resource allocation. After 17 years of restructuring, China's primary-level response capabilities towards public health emergencies have greatly improved. During the coronavirus disease 2019 epidemic, primary-level administrative and medical personnel, social organisations, volunteers, etc. have played a significant role in providing professional services utilising the primary-level emergency response system of 17 years. However, China's organisations did not learn their lesson from the SARS epidemic, and certain problems are exposed in the system. By analysing the experience and shortcomings of China's disease prevention and control system at the primary level, we can focus on the development of disease control systems for major epidemics in the future.

Analysis on the contribution rates of point and area source emissions to wuhan SO2, NO2, PM2.5 concentrations and atmospheric environmental capacity

Knowing the contribution rates and sharing rate of local source emissions to the atmospheric environmental capacity (AEC) is of great significance to the formulation of regional air pollution source control measures. Based on WRF-CALPUFF coupling models and the second pollution source survey data, Wuhan was taken as the research area, and the contribution rates of point and area source emissions to the SO2, NO2 and PM2.5 concentration in national pollutant control points (abbreviated as "national control points"), the AEC and its source emission sharing rate of each region were calculated. The results showed that WRF-CALPUFF had better reproducibility, the contribution rates of different pollution source emissions to the SO2, NO2 and PM2.5 concentration in national control points had obvious spatial distribution characteristics, and the contribution rates of key point sources to the SO2 concentration of each national control point exceeded 40%, while the contribution rates of the main urban area source to the NO2 and PM2.5 concentrations exceed 60%;the AEC of SO2, NO2 and PM2.5 in different regions had obvious seasonal and spatial changes, and the source emissions of NO2 and PM2.5 in the main urban area were 8.7 times and 3 times of its AEC, respectively. The calculation results from source sharing rate of regional AEC showed that the AEC of SO2 was mainly shared by point sources, and the AEC of NO2 and PM2.5 was mainly shared by area sources, but the sharing rate of SO2, NO2 and PM2.5 AEC from different regional source emissions showed different characteristics. The analysis of air quality improvement during the 7th Military World Games in 2019 and the COVID-19 pandemic in 2020 shows that the calculation formula about regional source sharing rate of AEC proposed in this paper is reasonable and the implementation of refined control to regional source emissions with the source sharing rate of regional AEC plays an important role on the continued improvement of Wuhan air quality.

Establishment of a psychological intervention mechanism for healthcare workers facing public health emergencies in the context of the COVID-19 outbreak.

The novel coronavirus disease pandemic is an unprecedented challenge globally. Medical personnel have been playing a leading role by fighting at the forefront against the pandemic and are the backbone of the fight against the epidemic. These frontline medical workers are under enormous psychological pressure and are prone to overwork and stress, as well as depression depletion, anxiety, insomnia, frustration, or self-blame in the face of patient deaths. Active psychological crisis interventions for medical staff fighting the pandemic are important protect and promote to maintain their occupational health. Based on China's experience, this paper describes the importance of organizational leadership, emergency psychological crisis interventions in pandemics, and psychological intervention measures for medical staff. It cites useful explorations from different regions and makes suggestions for establishing a sound psychological intervention mechanism.

The effect of the synchronized multi-dimensional policies on imported COVID-19 curtailment in China.

As countries are lifting restrictions and resuming international travels, the rising risk of COVID-19 importation remains concerning, given that the SARS-CoV-2 virus could be transmitted unintentionally through the global transportation network. To explore and assess the effective strategies for curtailing the epidemic risk from international importation nationwide, we evaluated "the joint prevention and control" mechanism, which made up of 19 containment policies, on how it impacted the change of medical observation and detection time from border arrival to laboratory confirmation of COVID-19 in its burst in China. Based on 1,314 epidemiological-survey cases from February 29 to May 25, 2020, we found that the synchronized approach of implementing multi-dimensional interventional policies, such as a centralized quarantine and nucleic acid testing (NAT), flight service adjustment and border closure, effectively facilitate early identification of infected case. Specifically, the implementation of the international flight service reduction was found to be associated with a reduction of the mean intervals of diagnosis from arrival to lab-confirmation by 0.44 days maximally, and the border closure was associated with a reduction of the diagnosis interval of imported cases by 0.69 days, from arrival to laboratory confirmation. The study suggests that a timely and synchronized implementation of multi-dimensional policies is compelling in preventing domestic spreading from importation.

Investigation of the Potential Mechanism Governing the Effect of the Shen Zhu San on COVID-19 by Network Pharmacology.

BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection has emerged in Wuhan and rapidly spread throughout China and even to other countries. Combined therapy with modern medicine and traditional Chinese medicine has been proposed, in which Shen Zhu San (SZS) was regarded as one of the basic prescriptions. METHODS: Network pharmacological approaches along with candidate compound screening, target prediction, target tissue location, protein-protein interaction network, gene ontology (GO), KEGG enrichment analyses, and gene microarray analyses were applied. RESULTS: A total of 627 targets of the 116 active ingredients of SZS were identified. Targets in immune cells and tissues were much more abundant than those in other tissues. A total of 597 targets were enriched in the GO biological cellular process, while 153 signaling pathways were enriched according to the KEGG analysis. A total of 450 SARS-related targets were integrated and intersected with the targets of SZS to identify 40 common targets that were significantly enriched in five immune function aspects of the immune system process during GO analysis. Several inflammation-related pathways were found to be significantly enriched throughout the study. CONCLUSIONS: The therapeutic mechanisms of the effects of SZS on COVID-19 potentially involve four effects: suppressing cytokine storms, protecting the pulmonary alveolar-capillary barrier, regulating the immune response, and mediating cell death and survival.

Comparison between two types of control strategies for the coronavirus disease 2019 pandemic.

Different countries have employed various strategies for controlling the coronavirus disease (COVID-19) pandemic because there is no consensus regarding effective control measures in the literature. Epidemic control strategies can be classified into two types based on their characteristics. The first type is the "severe acute respiratory syndrome (SARS)-like epidemic control strategy," i.e., containment. The second type is the "influenza pandemic-like epidemic control strategy" (flu pandemic-like strategy), i.e., mitigation. This paper presents a comparative analysis on the prevention and control strategies for COVID-19 in different countries to provide a reference to control the further spread of the pandemic.