Evaluation of efficacy and safety of Qiangzhu-qinggan formula as an adjunctive therapy in adult patients with severe influenza: study protocol for a randomized parallel placebo-controlled double-blind multicenter trial.

BACKGROUND: Influenza can fall into three categories according to severity: mild influenza, severe influenza, and critical influenza. Severe influenza can result in critical illness and sometimes death particularly in patients with comorbidities, advanced age, or pregnancy. Neuraminidase inhibitors (NAIs) are the only antiviral drugs in widespread use for influenza. However, the effectiveness of NAIs against severe influenza is uncertain. New effective drugs or regimens are therefore urgently needed. Qiangzhu-qinggan (QZQG) formula has been found to be effective against influenza virus infection during long-term application in China, which lacks support of evidence-based clinical trial till now. This study is designed to assess the efficacy and safety of QZQG formula as an adjuvant therapy in adult patients with severe influenza. METHODS: This protocol is drawn up in accordance with the SPIRIT guidelines and CONSORT Extension for Chinese herbal medicine formulas. This is a randomized, placebo-controlled, double-blind, multicenter trial. Two hundred twenty-eight adults with severe influenza are randomly assigned in a 1:1 ratio to QZQG or placebo for 7 days. All participants need to receive 1 day of screening before randomization, 7 days of intervention, and 21 days of observation after randomization. The primary outcome is the proportion of clinical improvement, defined as the proportion of patients who met the criteria of 3 points or less in the seven-category ordinal scale or 2 points or less in National Early Warning Score 2 within 7 days after randomization. DISCUSSION: This is the first randomized, controlled, parallel, double-blind clinical trial to evaluate the efficacy and safety of traditional Chinese herbal formula granules as an adjuvant therapy in adult patients with severe influenza. This study aims to redefine the value of traditional Chinese herbal medicines in the treatment of virus-related respiratory infectious diseases and serves as an example of evidence-based clinical trials of other Chinese herbal medicines.

Proteomic screening identifies RPLp2 as a specific regulator for the translation of coronavirus.

Viral mRNA of coronavirus translates in an eIF4E-dependent manner, and the phosphorylation of eIF4E can modulate this process, but the role of p-eIF4E in coronavirus infection is not yet entirely evident. p-eIF4E favors the translation of selected mRNAs, specifically the mRNAs that encode proteins associated with cell proliferation, inflammation, the extracellular matrix, and tumor formation and metastasis. In the present work, two rounds of TMT relative quantitative proteomics were used to screen 77 cellular factors that are upregulated upon infection by coronavirus PEDV and are potentially susceptible to a high level of p-eIF4E. PEDV infection increased the translation level of ribosomal protein lateral stalk subunit RPLp2 (but not subunit RPLp0/1) in a p-eIF4E-dependent manner. The bicistronic dual-reporter assay and polysome profile showed that RPLp2 is essential for translating the viral mRNA of PEDV. RNA binding protein and immunoprecipitation assay showed that RPLp2 interacted with PEDV 5'UTR via association with eIF4E. Moreover, the cap pull-down assay showed that the viral nucleocapsid protein is recruited in m7GTP-precipitated complexes with the assistance of RPLp2. The heterogeneous ribosomes, which are different in composition, regulate the selective translation of specific mRNAs. Our study proves that viral mRNA and protein utilize translation factors and heterogeneous ribosomes for preferential translation initiation. This previously uncharacterized process may be involved in the selective translation of coronavirus.

Small-Molecule RAF265 as an Antiviral Therapy Acts against PEDV Infection.

Porcine epidemic diarrhea virus (PEDV), a member of the family Coronaviridae, causes acute diarrhea, vomiting, dehydration, and high mortality in newborn piglets, and has caused significant economic losses in the pig industry. There are currently no specific drugs available to treat PEDV. Viruses depend exclusively on the cellular machinery to ensure an efficient replication cycle. In the present study, we found that small-molecule RAF265, an anticancer drug that has been shown to be a potent inhibitor of RAF, reduced viral loads of PEDV by 4 orders of magnitude in Vero cells, and protected piglets from virus challenge. RAF265 reduced PEDV production by mediating cytoskeleton arrangement and targeting the host cell's translation machinery. Treatment with RAF265 inhibited viral entry of PEDV S-glycoprotein pseudotyped viral vector particle (PEDV-pp), at half maximal effective concentrations (EC50) of 79.1 nM. RAF265 also presented potent inhibitory activity against viral infection by SARS-CoV-2-pp and SARS-CoV-pp. The present work may provide a starting point for further progress toward the development of antiviral strategies effective against coronavirus PEDV.

The Effects of the Coronavirus Disease Pandemicon Intravenous Thrombolytic Therapy in Patients with Acute Ischemic Stroke in Dalian, China (preprint)

Objective: We investigated the influence of the coronavirus disease (COVID-19) pandemic on the number of patients with acute ischemic stroke who received intravenous thrombolytic therapy (ITT) in Dalian, China, in 2020.  Methods: This retrospective descriptive study examined 13 stroke emergency map-participating hospitals in Dalian from February 1, 2020, to August 31, 2020. In this “stroke emergency map” of China, patients follow the official WeChat “Stroke Map” account and dial 120 for emergency medical services. We analyzed the number of patients with acute ischemic stroke who underwent ITT. In particular, we examined the onset-to-door time, door-to-needle time (DNT), onset-to-needle time, modes of transportation to the hospital, and National Institutes of Health Stroke Scale (NIHSS) scores before and after ITT. Data were collected for the aforementioned period and compared with the 2021 baseline data from the same period. The Mann‒Whitney U test was performed for data analysis.  Results: Compared with the data from 2020, the number of patients with acute ischemic stroke who underwent ITT increased (from 739 to 1719 cases) in 2021, as did the DNT (from 59 to 45 minutes; P=0.002). Moreover, 83.9% of patients presented to the hospital without ambulance transport versus 81.1% of patients in the 2021 non-COVID-19 pandemic period. Patients with NIHSS scores of 6-14 were more likely to call an ambulance for transport to the hospital than to self-admit to the emergency department.  Conclusions: During the 2020 COVID-19 pandemic, the DNT increased owing to increased surveillance of fever. Furthermore, the number of patients with acute ischemic stroke who underwent ITT also increased in 2021. However, these increases benefited from both the “stroke emergency map” of China and the “green channel,” a novel treatment approach that focuses on the rational design of the rescue process.

Inclusive leadership and emotional labor strategies of frontline medical staff: Regulatory focus as a mediator

In this study we examined inclusive leadership as an important factor in promoting the emotional labor strategies of frontline medical staff, and investigated the role of work regulatory focus as a mediator in this relationship. Data were collected from 52 supervisors and 231 frontline medical staff employed at 15 hospitals in China. We found that inclusive leadership inspired frontline medical staff to engage more in deep acting than in surface acting. Further, work regulatory focus played a mediating role in the relationship between inclusive leadership and subordinates' emotional labor strategy. Promotion focus positively affected deep acting and negatively affected surface acting, and prevention focus positively affected both surface acting and deep acting. Theoretical and practical management implications are discussed.

Immunocapture Magnetic Beads Enhanced the LAMP-CRISPR/Cas12a Method for the Sensitive, Specific, and Visual Detection of Campylobacter jejuni.

Campylobacter jejuni is one of the most important causes of food-borne infectious disease, and poses challenges to food safety and public health. Establishing a rapid, accurate, sensitive, and simple detection method for C. jejuni enables early diagnosis, early intervention, and prevention of pathogen transmission. In this study, an immunocapture magnetic bead (ICB)-enhanced loop-mediated isothermal amplification (LAMP) CRISPR/Cas12a method (ICB-LAMP-CRISPR/Cas12a) was developed for the rapid and visual detection of C. jejuni. Using the ICB-LAMP-CRISPR/Cas12a method, C. jejuni was first captured by ICB, and the bacterial genomic DNA was then released by heating and used in the LAMP reaction. After the LAMP reaction, LAMP products were mixed and detected by the CRISPR/Cas12a cleavage mixture. This ICB-LAMP-CRISPR/Cas12a method could detect a minimum of 8 CFU/mL of C. jejuni within 70 min. Additionally, the method was performed in a closed tube in addition to ICB capture, which eliminates the need to separate preamplification and transfer of amplified products to avoid aerosol pollution. The ICB-LAMP-CRISPR/Cas12a method was further validated by testing 31 C. jejuni-positive fecal samples from different layer farms. This method is an all-in-one, simple, rapid, ultrasensitive, ultraspecific, visual detection method for instrument-free diagnosis of C. jejuni, and has wide application potential in future work.

The Power of Sustainability in the 'Black Swan';Event: Entrepreneurial Cognition of Top Management Team and Dual Business Model Innovation

In the dynamic environment where 'Black Swan';events occur frequently, the dual business model innovation (DBMI) which has both proactive and reactive characteristics is the core force for the enterprises to turn crises into opportunities and achieve their survival and sustainability. However, prevailing views do not clearly explain how to drive dual business model innovation. Based on the upper echelon theory, this study developed a multiple mediation model, which links entrepreneurial cognition of the top management team (TMT), knowledge search with dual business model innovation. By taking the data of 217 TMTs, the hypotheses are verified. The results show that TMT's configuration cognition, willing cognition, and ability cognition all have a positive effect on both proactive and reactive business model innovation. Knowledge search acts as a 'bridge';between TMT's entrepreneurial cognition and DBMI. Greater entrepreneurial cognition can guide exploratory and exploitative knowledge searches and promote the DBMI. The results also show the mediating effect between different entrepreneurial cognition and DBMI is not completely consistent, and a partial mediation effect exists associating configuration cognition with DBMI, but a full mediation effect is present between other cognitions and DBMI. These results provide more understanding to the formation of dual business model innovation under the impact of COVID-19.

Coronavirus GenBrowser for monitoring the transmission and evolution of SARS-CoV-2.

Genomic epidemiology is important to study the COVID-19 pandemic, and more than two million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences were deposited into public databases. However, the exponential increase of sequences invokes unprecedented bioinformatic challenges. Here, we present the Coronavirus GenBrowser (CGB) based on a highly efficient analysis framework and a node-picking rendering strategy. In total, 1,002,739 high-quality genomic sequences with the transmission-related metadata were analyzed and visualized. The size of the core data file is only 12.20 MB, highly efficient for clean data sharing. Quick visualization modules and rich interactive operations are provided to explore the annotated SARS-CoV-2 evolutionary tree. CGB binary nomenclature is proposed to name each internal lineage. The pre-analyzed data can be filtered out according to the user-defined criteria to explore the transmission of SARS-CoV-2. Different evolutionary analyses can also be easily performed, such as the detection of accelerated evolution and ongoing positive selection. Moreover, the 75 genomic spots conserved in SARS-CoV-2 but non-conserved in other coronaviruses were identified, which may indicate the functional elements specifically important for SARS-CoV-2. The CGB was written in Java and JavaScript. It not only enables users who have no programming skills to analyze millions of genomic sequences, but also offers a panoramic vision of the transmission and evolution of SARS-CoV-2.

Current state of research about acupuncture for the treatment of COVID-19: A scoping review.

BACKGROUND: Since the outbreak of coronavirus disease (COVID-19), acupuncture has been widely used in the treatment of COVID-19. The research community has responded rapidly and has already published many research articles about this topic. METHODS: We searched PubMed, Embase, Cochrane Library as well as CNKI, Wanfang and VIP from January 1, 2020 to July 31, 2021. The dates of publication, language of publication, methodological characteristics and the key findings were analyzed separately. The data are presented as bar graphs, structured tables and figures. RESULTS: In this scoping review, 16 research articles were included: 7 case reports, 6 observational studies, 1 review, 1 RCT and 1 nonrandomized clinical trial. The majority of the articles (81.3%) were published by Chinese scholars, 12.5% articles were by scholars in the United States, and 6.3% articles were by scholars in Iran. The included studies reported that acupuncture could alleviate the symptoms of COVID-19 patients, shorten their hospitalization days, and is effective for the elderly. There were no side effects reported. The most frequent acupoints used were LI4, PC6, ST36 and KI3. They reported many obstacles in implementing acupuncture therapy for treating COVID-19 patients. CONCLUSION: Acupuncture has a good effect for the treatment of COVID-19, but high-quality evidence support is still lacking. Coupled with the difficulties that acupuncturists experienced during the process of treatment, the promotion of acupuncture treatment for COVID-19 faces many obstacles.

Lung Function In Discharged Patients After Coronavirus Infection (SARS, MERS, COVID-19): A Systemic Review And Meta-Analysis (preprint)

Background: To date, coronaviruses have caused three pandemics. Fewer studies concentrated on the prognosis of lung function.Objective: To summarize the lung function of the discharged after coronavirus infection.Methods: We systematically searched PubMed, Cochrane Library, Web of Science, and EMBASE. Two authors independently screened articles and extracted data. On average, predicted values and damage rates of seven lung function indices were pooled by single-arm meta-analysis. And, in severe/critical vs. non-severe/critical and one-year follow-up, they were pooled by two-arm meta-analysis. The source of high heterogeneity was explored by meta-regression or subgroup analysis. Results: Of the 7798 articles identified, 34 studies were included. On average, the pooled predicted values of the seven indices were within normal except for DLCO (79.2, 95% CI (76.2－82.2 )). Damage of lung function indices accounted for 6.2－35.2% of the discharged with DLCO most, and 83－100% of the damage was mild. Meta-regression showed that different viruses, countries, disease settings, and measurement times were not the source of high heterogeneities. In severe/critical illness vs. non-severe/critical, predicted values of seven indices were significantly lower (largest gap in DLCO (WMD -11.60, 95% CI -14.23－-8.98)). However, damage rates got rises only in DLCO (RR 1.74, 95% CI 1.46－2.07) and TLC, having no differences in the other indices. In one-year follow-up, predicted values were significantly improved in the severe/critical subgroup, while having no change in the non-severe/critical subgroup. Damage rates got no improvement in all indices.Interpretation: A single predicted value or damage rate can't give a clear description of lung function after coronavirus infection, and the trends of the two are sometimes inconsistent. We suggest more prospective cohort or follow-up studies in the future to lessen the influence of differences in lung function measurements across studies.Registration: PROSPERO (CRD42020192843)

An online coronavirus analysis platform from the National Genomics Data Center.

Since the first reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic, spreading to more than 200 countries and regions worldwide. With continued research progress and virus detection, SARS-CoV-2 genomes and sequencing data have been reported and accumulated at an unprecedented rate. To meet the need for fast analysis of these genome sequences, the National Genomics Data Center (NGDC) of the China National Center for Bioinformation (CNCB) has established an online coronavirus analysis platform, which includes de novoassembly, BLAST alignment, genome annotation, variant identification, and variant annotation modules. The online analysis platform can be freely accessed at the 2019 Novel Coronavirus Resource (2019nCoVR) (https://bigd.big.ac.cn/ncov/online/tools).

Medical waste management practice during the 2019-2020 novel coronavirus pandemic: Experience in a general hospital.

It is currently a critical period for the prevention and control of the COVID-19 pandemic. Since the medical waste disposal could be an important way to control the source of infection, standardization, and strict implementation of the management of COVID-19 related medical waste should be with careful consideration to reduce the risk of epidemic within hospitals. This study illustrates the practice of medical waste disposal responding to the 2019-2020 novel coronavirus pandemic.

Three kinds of treatment with Homoharringtonine, Hydroxychloroquine or shRNA and their combination against coronavirus PEDV in vitro.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) of the family Coronaviridae has caused substantial economic losses in the swine husbandry industry. There's currently no specific drug available for treatment of coronaviruses or PEDV. METHOD: In the current study, we use coronavirus PEDV as a model to study antiviral agents. Briefly, a fusion inhibitor tHR2, recombinant lentivirus-delivered shRNAs targeted to conserved M and N sequences, homoharringtonine (HHT), and hydroxychloroquine (HCQ) were surveyed for their antiviral effects. RESULTS: Treatment with HCQ at 50 µM and HHT at 150 nM reduced virus titer in TCID50 by 30 and 3.5 fold respectively, and the combination reduced virus titer in TCID50 by 200 fold. CONCLUSION: Our report demonstrates that the combination of HHT and HCQ exhibited higher antiviral activity than either HHT or HCQ exhibited. The information may contribute to the development of antiviral strategies effective in controlling PEDV infection.

Viral Sepsis, No Neglecting Complication Following Novel Corona Virus Disease (COVID-19) (preprint)

Background Until 24:00 of April 26th 2020, 2,918,268 laboratory-confirmed cases of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection have been reported worldwide, including 203,528 deaths. Bacterial infection is the main cause of sepsis, however, sepsis caused by virus is often ignored. Increased awareness, early recognition of viral sepsis, rapid administration of appropriate antiviral drugs, and urgent treatment can significantly reduce deaths of viral sepsis.Objectives Given the rapid global spread of novel Corona Virus Disease (COVID-19), coupled with the high rate of missed diagnosis of viral sepsis caused by SARS-CoV-2 infection, it is urgent to evaluate the multiple organ failure score and viral sepsis in COVID-19 patients, so as to determine the clinical characteristics of viral sepsis more accurately and reveal the risk factors related to mortality.Methods Here we provide a full description of three cases of viral sepsis and subsequent multiple organ dysfunction (MODS) caused by SARS-CoV-2 infection imported to Guiyang from Wuhan.Results Complete laboratory examination, imaging data and treatment methods for the patients are analyzed. Sepsis-related Organ Failure Assessment score (SOFA score) and Multiple organ dysfunction scores (MOD score) were daily assessed, aim to elucidate the clinical feature of viral sepsis and MODS and to attract enough attention by clinicians.Conclusions Therefore, we strongly suggest to daily evaluate SOFA score and MOD score in severe and critically-ill COVID-19 patients, so as to early diagnose and prevention of sepsis and MODS.

The 2019 novel coronavirus resource.

An ongoing outbreak of a novel coronavirus infection in Wuhan, China since December 2019 has led to 31,516 infected persons and 638 deaths across 25 countries (till 16:00 on February 7, 2020). The virus causing this pneumonia was then named as the 2019 novel coronavirus (2019-nCoV) by the World Health Organization. To promote the data sharing and make all relevant information of 2019-nCoV publicly available, we construct the 2019 Novel Coronavirus Resource (2019nCoVR, https://bigd.big.ac.cn/ncov). 2019nCoVR features comprehensive integration of genomic and proteomic sequences as well as their metadata information from the Global Initiative on Sharing All Influenza Data, National Center for Biotechnology Information, China National GeneBank, National Microbiology Data Center and China National Center for Bioinformation (CNCB)/National Genomics Data Center (NGDC). It also incorporates a wide range of relevant information including scientific literatures, news, and popular articles for science dissemination, and provides visualization functionalities for genome variation analysis results based on all collected 2019-nCoV strains. Moreover, by linking seamlessly with related databases in CNCB/NGDC, 2019nCoVR offers virus data submission and sharing services for raw sequence reads and assembled sequences. In this report, we provide comprehensive descriptions on data deposition, management, release and utility in 2019nCoVR, laying important foundations in aid of studies on virus classification and origin, genome variation and evolution, fast detection, drug development and pneumonia precision prevention and therapy.