FEN1-aided recombinase polymerase amplification (FARPA) for one-pot and multiplex detection of nucleic acids with an ultra-high specificity and sensitivity.

Recombinase polymerase amplification (RPA) running at 37-42 °C is fast, efficient and less-implemented; however, the existing technologies of nucleic acid testing based on RPA have some limitations in specificity of single-base recognition and multiplexing capability. Herein, we report a highly specific and multiplex RPA-based nucleic acid detection platform by combining flap endonuclease 1 (FEN1)-catalysed invasive reactions with RPA, termed as FEN1-aided RPA (FARPA). The optimal conditions enable RPA and FEN1-based fluorescence detection to occur automatically and sequentially within a 25-min turnaround time and FARPA exhibits sensitivity to 5 target molecules. Due to the ability of invasive reactions in discriminating single-base variation, this one-pot FARPA is much more specific than the Exo probe-based or CRISPR-based RPA methods. Using a universal primer pair derived from tags in reverse transcription primers, multiplex FARPA was successfully demonstrated by the 3-plex assay for the detection of SARS-CoV-2 pathogen (the ORF1ab, the N gene, and the human RNase P gene as the internal control), the 2-plex assay for the discrimination of SARS-CoV-2 wild-type from variants (Alpha, Beta, Epsilon, Delta, or Omicrons), and the 4-plex assay for the screening of arboviruses (zika virus, tick-borne encephalitis virus, yellow fever virus, and chikungunya virus). We have validated multiplex FARPA with 103 nasopharyngeal swabs for SARS-CoV-2 detection. The results showed a 100% agreement with RT-qPCR assays. Moreover, a hand-held FARPA analyser was constructed for the visualized FARPA due to the switch-like endpoint read-out. This FARPA is very suitable for pathogen screening and discrimination of viral variants, greatly facilitating point-of-care diagnostics.

Occupational Risk Factors for Physical and Mental Health in Primary Healthcare Providers: A National Cross-Sectional Survey from 62 Urban Communities in China.

Purpose: To understand the physical and mental health status of primary healthcare providers (PHPs) including physicians, nurses and other staff and the workplace risk factors for depression, anxiety and intention-to-leave. Patients and Methods: In December 2021, a national cross-sectional survey was conducted from 62 urban communities in China, and all PHPs were invited to complete a standardized questionnaire. Information on demographic, health-related lifestyle, cardiovascular risk factors and physical health status, occupational stress and intention-to-leave was collected. Depression and anxiety were assessed using the Zung Self-Rating Anxiety/Depression Scale (SAS/SDS). Results: A total of 4901 PHPs were included. 67.0% males currently drank alcohol vs 25.3% in females; 36.0% males currently smoked cigarettes vs 1.4% in females. Notably, more than half males were overweight or obese, but this proportion was 24.2% in females. The prevalence of chronic diseases, including hypertension, diabetes, dyslipidemia, non-alcoholic fatty liver disease, gout, and disease clustering were higher in males than in females. The prevalence of depression and anxiety were high, 50% had depression, of whom 15.6% had moderate/severe depression. Over 15% participants had varied levels of anxiety, and approximately 4% had moderate/severe anxiety. PHPs who aged 18-29 (OR: 1.31, 95% CI: 1.05-1.64), were males (OR: 1.34, 95% CI: 1.14-1.57), with lower professional title (comparing with staff with senior title, the ORs of the intermedium, junior and none were 1.83, 2.18 and 2.49, respectively), took charge in nursing (OR: 1.41, 95% CI: 1.20-1.65), with higher perceived stress level (OR: 1.82, 95% CI: 1.41-2.34), and suffering from severe fatigue (OR: 2.55, 95% CI: 1.99-3.27) were more likely to have depression. Likewise, PHPs who were younger, with intermedium professional title, had higher perceived pressure level, and higher fatigue levels were more likely to have anxiety. Conclusion: The mental health of PHPs is worrisome, with a high burden of chronic diseases and occupational risk factors. Younger PHPs, nurses, and those with higher levels of work pressure and fatigue are more vulnerable to psychological problems. The high prevalence of intention-to-leave calls for strategies that relieve the workplace stress and enhance the human resource capability.

Guardian Angels

FEATURES On December 28, 2022, Peking University Third Hospital (PUTH) received a thank you letter from the daughter of a patient they had treated four days earlier. In December last year, its outpatient department received more than 260,000 patient visits, with the average daily number of fever outpatients exceeding 1,200. In December last year, with a rapidly rising number of patients pouring in with COVID-19 symptoms, hospitals across China were swamped, their emergency departments in particular. [Extracted from the article] Copyright of Beijing Review is the property of Beijing Review and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Altered gut microbiota composition in children and their caregivers infected with the SARS-CoV-2 Omicron variant.

BACKGROUND: Gut microbiota alterations have been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19). This study aimed to explore gut microbiota changes in a prospective cohort of COVID-19 children and their asymptomatic caregivers infected with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) Omicron variant. METHODS: A total of 186 participants, including 59 COVID-19 children, 50 asymptomatic adult caregivers, 52 healthy children (HC), and 25 healthy adults (HA), were recruited between 15 April and 31 May 2022. The gut microbiota composition was determined by 16S rRNA gene sequencing in fecal samples collected from the participants. Gut microbiota functional profiling was performed by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software. RESULTS: The gut microbiota analysis of beta diversity revealed that the fecal microbial community of COVID-19 children remained far distantly related to HC. The relative abundances of the phyla Actinobacteria and Firmicutes were decreased, whereas Bacteroidetes, Proteobacteria, and Verrucomicrobiota were increased in COVID-19 children. Feces from COVID-19 children exhibited notably lower abundances of the genera Blautia, Bifidobacterium, Fusicatenibacter, Streptococcus, and Romboutsia and higher abundances of the genera Prevotella, Lachnoclostridium, Escherichia-Shigella, and Bacteroides than those from HC. The enterotype distributions of COVID-19 children were characterized by a high prevalence of enterotype Bacteroides. Similar changes in gut microbiota compositions were observed in asymptomatic caregivers. Furthermore, the microbial metabolic activities of KEGG (Kyoto Encyclopedia of Genes and Genomes) and COG (cluster of orthologous groups of proteins) pathways were perturbed in feces from subjects infected with the SARS-CoV-2 Omicron variant. CONCLUSION: Our data reveal altered gut microbiota compositions in both COVID-19 children and their asymptomatic caregivers infected with the SARS-CoV-2 Omicron variant, which further implicates the critical role of gut microbiota in COVID-19 pathogenesis.

Association of Workplace Bullying with Suicide Ideation and Attempt Among Chinese Nurses During the COVID-19 Pandemic.

Nurses experience a high incidence of workplace bullying and are at a higher risk of suicide than the general population. However, there is no empirical evidence on how exposure to workplace bullying is associated with suicide ideation and attempts among nurses. Nurses were recruited from tertiary hospitals in Shandong Province, China, using stratified cluster sampling. Suicide ideation and attempts were assessed using two items, and the Workplace Psychologically Violent Behaviors Instrument was used to measure subtypes of workplace bullying. The prevalence of workplace bullying, suicide ideation, and suicide attempts was 30.6%, 16.8%, and 10.8%, respectively. After adjusting for covariates, victims of workplace bullying were at a high risk of suicide ideation and attempts. Among workplace bullying subtypes, individuals' isolation from work and direct negative behaviors were predictors of both suicide ideation and attempts; attack on personality only predicted suicide attempts. The more bullying subtypes experienced by nurses, the greater their likelihood of suicide ideation and attempts. These findings suggested that workplace bullying was associated with an increased risk of suicide ideation and attempts in nurses, with both independent and cumulative risks. Interventions should focus on prevention and managing the effects of workplace bullying among nurses.

Strategies for screening, occupational prevention, and management of COVID-19 in outpatient clinics in Shandong

Objective We hope to analyze the information of outpatients in a tertiary care hospital during the epidemic of COVID-19, so as to formulate effective regulations for the prevention and control of COVID-19. Methods We collected information from outpatients from January 28, 2020 to March 2, 2020 and performed the statistical analysis. Results During the study period, there were more than 60,000 outpatients. Among them, 404 patients with a body temperature above 37.3°C who had not been to Wuhan and had no contact with people from Wuhan. There were 8 people who had contact with people from Wuhan, such as 4 people with fever, 3 people with normal body temperature but cough symptoms, and 1 person with normal body temperature and no other discomfort. There were 2 patients with high body temperature from the epidemic area in Wuhan, and one novel Coronavirus patient was confirmed as the final result. Conclusion During the COVID-19 pandemic, outpatient medical staff should enhance their awareness of protection, hospitals should standardize the outpatient COVID-19 prevention and control system, improve the prevention and emergency system, and reduce occupational exposure hazards and the occurrence of post-exposure infections.

Implementation and challenges to preventing the re-establishment of malaria in China in the COVID-19 era.

BACKGROUND: The rapid emergence and global spread of COVID-19 have caused substantial global disruptions that have impacted malaria programs worldwide. Innovative strategies to enable countries aiming to eliminate malaria as well as those that are already certified as malaria-free, are needed to address malaria importation in the context of the COVID-19 pandemic. China was certified as malaria-free in 2021 and now aims to prevent the malaria re-establishment. Nonpharmaceutical interventions such as entry screening, quarantining, and health education for individuals returning from international travel during the COVID-19 pandemic present both opportunities and challenges to the management of imported malaria. This study aimed to describe and analyze the operational challenges associated with an integrated surveillance and case management program in which malaria re-establishment prevention measures were incorporated into the COVID-19 program in China. METHODS: After the integration of malaria re-establishment prevention activities into the COVID-19 program for 10 months in Jiangsu Province, China, a focus-group discussion of public health workers working on preventing malaria re-establishment and controlling COVID-19 was held in June 2021, aiming to explore the operational challenges and lessons learned from the integrated approach. RESULTS: From 01 August 2020 to 31 May 2021, 8,947 overseas travelers with Yangzhou as the final destination underwent 14-day managed quarantine and 14-day home isolation. Of these travelers, 5,562 were from malaria-endemic regions. A total of 26,026 education booklets and materials were distributed to expand malaria-related knowledge. Twenty-two patients with unknown fever were screened for malaria with rapid diagnostic tests, and one patient was confirmed to have imported malaria. The challenges associated with the implementation of the integrated malaria surveillance and case management program include neglect of malaria due to COVID-19, lack of a standard operating procedure for malaria screening, mobility of public health providers, and difficulties in respecting the timeline of the "1-3-7" surveillance strategy. CONCLUSIONS: China's experience highlights the feasibility of integrated case surveillance and management of existing infectious diseases and new emerging infections. It also demonstrates the importance of a sound public health infrastructure with adequate, trained field staff for screening, testing, contact tracing, and providing health education, all of which are crucial for the success of both malaria re-establishment prevention program and the effective control of COVID-19.

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The global pandemic of coronavirus disease 2019 (COVID-19) has brought great challenges to the traditional medical model. During the outbreak of COVID-19 in Shanghai, China, from March to May, 2022, there was a significant increase in the number of pediatric cases due to high transmissibility, immune escape, and vaccine breakthrough capacity of Omicron variants. The designated hospitals for children with COVID-19 served as a connecting link between children's specialized hospitals and mobile cabin hospitals. From April 7 to June 2, 2022, a total of 871 children with COVID-19 were admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine (South Branch), a designated hospital for children with COVID-19. Among these patients, 568 (65.2%) were children under 3 years old, 870 (99.9%) were mild or moderate, and 1 was severe. This article reports the experience in the management of pediatric cases in this designated hospital, which included the following aspects: establishing an optimal case-admission process; strengthening multidisciplinary standardized diagnosis and treatment; optimizing the management, warning, and rescue system for severe COVID-19; implementing family-centered nursing care; formulating an individualized traditional Chinese medicine treatment regimen; optimizing the discharge process and strengthening bed turnover; implementing strict whole-process control to reduce the risk of nosocomial infection; constructing a structured medical record system and using information platforms to adapt to the work mode of large-volume cases; conducting scientific research and sharing the experience in diagnosis and treatment.

Emerging trends of research on mRNA vaccines: A co-citation analysis.

This study was designed to evaluate the emerging trends of research on mRNA vaccines. Altogether 3056 research articles related to mRNA vaccines published since 2010 were retrieved from the Web of Science database, based on which a co-citation analysis was conducted using CiteSpace. A total of 12 clusters were derived, all of which were classified into three periods according to the content and publication time of articles: (1) The preliminary exploratory period before early 2010s, when the potential of mRNA to induce immune response was evaluated; (2) the growing up period from early 2010s to 2019, when the stability and immunogenicity of mRNA vaccines were improved and the clinical development of products were pushed forward; (3) the rapid maturity period after the outbreak of COVID-19, when two products for COVID-19 were authorized for the first time. The approval of COVID-19 vaccines is an encouraging start, while the enormous potential of mRNA vaccines remains to be explored. Future research on mRNA-based infectious disease vaccines will focus on further optimizing mRNA modification and delivery, solving problems of the approved vaccines in real world, investigating mRNA vaccines for other infectious indications, and developing self-amplifying or thermostable vaccines. Future research on mRNA-based therapeutic cancer vaccines will focus on screening proper neoantigens, enhancing the delivery of mRNA into antigen-presenting cells and overcoming suppressive tumor microenvironment.

SARS-CoV-2 impacts the transcriptome and epigenome at the maternal-fetal interface in pregnancy (preprint)

During pregnancy, the maternal-fetal interface plays vital roles in fetal development. Its disruption is frequently found in pregnancy complications. Recent works show increased incidences of adverse pregnancy outcomes in COVID-19 patients; however, the mechanism remains unclear. Here, we analyzed the molecular impacts of SARS-CoV-2 infection on the maternal-fetal interface. Generating bulk and single-nucleus transcriptomic and epigenomic profiles from COVID-19 patients and control samples, we discovered aberrant immune activation and angiogenesis patterns in patients. Surprisingly, retrotransposons were dysregulated in specific cell types. Notably, reduced enhancer activities of LTR8B elements were functionally linked to the downregulation of Pregnancy-Specific Glycoprotein genes in syncytiotrophoblasts. Our findings revealed that SARS-CoV-2 infection induced significant changes to the epigenome and transcriptome at the maternal-fetal interface, which may be associated with pregnancy complications.

In vivo antiviral effect of plant essential oils against avian infectious bronchitis virus.

BACKGROUND: Infectious bronchitis virus (IBV) leads to huge economic losses in the poultry industry worldwide. The high levels of mutations of IBV render vaccines partially protective. Therefore, it is urgent to explore an effective antiviral drug or agent. The present study aimed to investigate the in vivo anti-IBV activity of a mixture of plant essential oils (PEO) of cinnamaldehyde (CA) and glycerol monolaurate (GML), designated as Jin-Jing-Zi. RESULTS: The antiviral effects were evaluated by clinical signs, viral loads, immune organ indices, antibody levels, and cytokine levels. The infection rates in the PEO-M (middle dose) and PEO-H (high dose) groups were significantly lower than those in the prevention, positive drug, and PEO-L (low dose) groups. The cure rates in the PEO-M and PEO-H groups were significantly higher than those in the prevention, positive drug, and PEO-L groups, and the PEO-M group had the highest cure rate of 92.31%. The symptom scores and IBV mRNA expression levels were significantly reduced in the PEO-M group. PEO significantly improved the immune organ indices and IBV-specific antibody titers of infected chickens. The anti-inflammatory factor levels of IL-4 and IFN-γ in the PEO-M group maintained high concentrations for a long time. The IL-6 levels in the PEO-M group were lower than those in prevention, positive drug, and PEO-L groups. CONCLUSION: The PEO had remarkable inhibition against IBV and the PEO acts by inhibiting virus multiplication and promoting immune function, suggesting that the PEO has great potential as a novel anti-IBV agent for inhibiting IBV infection.

Construction of Influenza Early Warning Model Based on Combinatorial Judgment Classifier: A Case Study of Seasonal Influenza in Hong Kong.

OBJECTIVE: The annual influenza epidemic is a heavy burden on the health care system, and has increasingly become a major public health problem in some areas, such as Hong Kong (China). Therefore, based on a variety of machine learning methods, and considering the seasonal influenza in Hong Kong, the study aims to establish a Combinatorial Judgment Classifier (CJC) model to classify the epidemic trend and improve the accuracy of influenza epidemic early warning. METHODS: The characteristic variables were selected using the single-factor statistical method to establish the influencing factor system of an influenza outbreak. On this basis, the CJC model was proposed to provide an early warning for an influenza outbreak. The characteristic variables in the final model included atmospheric pressure, absolute maximum temperature, mean temperature, absolute minimum temperature, mean dew point temperature, the number of positive detections of seasonal influenza viruses, the positive percentage among all respiratory specimens, and the admission rates in public hospitals with a principal diagnosis of influenza. RESULTS: The accuracy of the CJC model for the influenza outbreak trend reached 96.47%, the sensitivity and specificity change rates of this model were lower than those of other models. Hence, the CJC model has a more stable prediction performance. In the present study, the epidemic situation and meteorological data of Hong Kong in recent years were used as the research objects for the construction of the model index system, and a lag correlation was found between the influencing factors and influenza outbreak. However, some potential risk factors, such as geographical nature and human factors, were not incorporated, which ideally affected the prediction performance to some extent. CONCLUSION: In general, the CJC model exhibits a statistically better performance, when compared to some classical early warning algorithms, such as Support Vector Machine, Discriminant Analysis, and Ensemble Classfiers, which improves the performance of the early warning of seasonal influenza.

COVIDSum: A linguistically enriched SciBERT-based summarization model for COVID-19 scientific papers.

The coronavirus disease (COVID-19) has claimed the lives of over 350,000 people and infected more than 173 million people worldwide, it triggers researchers from diverse fields are accelerating their research to help diagnostics, therapies, and vaccines. Researchers also publish their recent research progress through scientific papers. However, manually writing the abstract of a paper is time-consuming, and it increases the writing burden of the researchers. Abstractive summarization technique which automatically provides researchers reliable draft abstracts, can alleviate this problem. In this work, we propose a linguistically enriched SciBERT-based summarization model for COVID-19 scientific papers, named COVIDSum. Specifically, we first extract salient sentences from source papers and construct word co-occurrence graphs. Then, we adopt a SciBERT-based sequence encoder and a Graph Attention Networks-based graph encoder to encode sentences and word co-occurrence graphs, respectively. Finally, we fuse the above two encodings and generate an abstractive summary of each scientific paper. When evaluated on the publicly available COVID-19 open research dataset, the performance of our proposed model achieves significant improvement compared with other document summarization models.

Colloidal dispersion of poly(ionic liquid)/Cu composite particles for protective surface coating against SAR-CoV-2.

Herein, we report a waterproof anti-SARS-CoV-2 protective film prepared by spray-coating of an aqueous colloidal dispersion of poly(ionic liquid)/copper (PIL/Cu) composite nanoparticles onto a substrate. The PIL dispersion was prepared by suspension polymerization of 3-dodecyl-1-vinylimdiazolium bromide in water at 70°C. The copper acetate salt was added into the PIL nanoparticle dispersion and in situ reduced into copper nanoparticles anchoring onto the PIL nanoparticles. Despite being waterborne, the PIL in bulk is intrinsically insoluble in water and the formed coating is stable in water. The formed surface coating by PIL/copper composite nanoparticles was able to deactivate SARS-CoV-2 virions by 90.0% in 30 minutes and thus may effectively prevent the spread of SARS-CoV-2 through surface contact. This method may provide waterborne dispersions for a broad range of antivirus protective surface coatings for both outdoor and indoor applications.

Safety, tolerability, pharmacokinetic characteristics, and immunogenicity of MW33: a Phase 1 clinical study of the SARS-CoV-2 RBD-targeting monoclonal antibody.

MW33 is a fully humanized IgG1κ monoclonal neutralizing antibody, and may be used for the prevention and treatment of coronavirus disease 2019 (COVID-19). We conducted a randomized, double-blind, placebo-controlled, single-dose, dose-escalation Phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of MW33. Healthy adults aged 18-45 years were sequentially enrolled into the 4, 10, 20, 40, and 60 mg/kg dose groups and infused with MW33 over 60 ± 15 min and followed for 85 days. All 42 enrolled participants completed the MW33 infusion, and 40 participants completed the 85-day follow-up period. 34 participants received a single infusion of 4 (n = 2), 10 (n = 8), 20 (n = 8), 40 (n = 8), and 60 mg/kg (n = 8) of MW33. 27 subjects in the test groups experienced 78 adverse events (AEs) post-dose, with an incidence of 79.4% (27/34). The most common AEs included abnormal laboratory test results, vascular and lymphatic disorders, and infectious diseases. The severity of AEs was mainly Grade 1 (92 AEs), and three Grade 2 and one Grade 4. The main PK parameters, maximum concentration (Cmax), and area under the concentration-time curve (AUC0-t, and AUC0-∞) in 34 subjects showed a linear kinetic relationship in the range of 10-60 mg/kg. The plasma half-life was approximately 25 days. The positive rates of serum ADAs and antibody titres were low with no evidence of an impact on safety or PK. In conclusion, MW33 was well-tolerated, demonstrated linear PK, with a lower positive rate of serum ADAs and antibody titres in healthy subjects.Trial registration: ClinicalTrials.gov identifier: NCT04427501.Trial registration: ClinicalTrials.gov identifier: NCT04533048.Trial registration: ClinicalTrials.gov identifier: NCT04627584.

Analysis of the comprehensive non-pharmaceutical interventions and measures in containing the COVID-19 epidemic in Shenzhen: a retrospective study.

OBJECTIVE: To analyse the epidemiological characteristics of family clusters of COVID-19 and the three stages of the comprehensive non-pharmaceutical interventions and measures implemented in Shenzhen. METHODS: The epidemic curve of COVID-19 was drawn and the impact of the comprehensive non-pharmaceutical interventions and measures was analysed by the different periods of the epidemic. RESULTS: A total of 427 cases (417 confirmed cases and 10 asymptomatic infectious cases) were reported in Shenzhen, of which 259 (60.7%) were clustered cases. 97 cluster events were drawn and most cluster events (97.3%) occurred in families. There were three stages of the COVID-19 epidemic in Shenzhen. The epidemic increased rapidly, but the peak lasted for a short time, while the decline in incidence was rapid and large. CONCLUSIONS: Family clusters were the main feature of the COVID-19 outbreak in Shenzhen in 2020, and the Shenzhen government rolled out a quick response to the epidemic. Non-pharmaceutical interventions and measures were proven to have effectively contained community transmission, limit the transmission to aggregation and reduce the scale of transmission within a household.