In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. ...For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.
Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern ...globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.
We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.
Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.
A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Idiopathic pulmonary fibrosis (IPF) is a chronic and usually progressive lung disease and the epithelial-mesenchymal transition (EMT) may play an important role in the pathogenesis of pulmonary ...fibrosis. IL-17 is a proinflammatory cytokine which promotes EMT profiles in lung inflammatory diseases. In this study, we investigated the effect of IL-17 on EMT in alveolar epithelial cell line A549 and the role of TGFβ1-Smad and ERK signaling pathways in the process. Morphological observation on the cells was performed under inverted microscope. The mRNA and protein expressions of E-cad and α-SMA were detected by quantitative RT-PCR and western blotting. The mRNA and protein expressions of TGF-β1 were analyzed via quantitative RT-PCR and ELISA. Expressions of Smad2/3, p-Smad2/3, ERK1/2, p-ERK1/2 and p-JNK were examined by western blotting. The results indicated that IL-17 can induce A549 cells to undergo morphological changes and phenotypic markers changes, such as down-regulated E-cad expression and up-regulated α-SMA expression. Additionally, IL-17 enhanced TGF-β1 expression and stimulated Smad2/3 and ERK1/2 phosphorylation in A549 cells. However, there were no significant differences in the expression of phosphorylated JNK in A549 cells with or without IL-17 treatment. SB431542 or U0126 treated cells showed inhibited morphological changes and phenotypic markers expression, such as up-regulated E-cad expression and down-regulated α-SMA expression. In summary, our results suggest that IL-17 can induce A549 alveolar epithelial cells to undergo EMT via the TGF-β1 mediated Smad2/3 and ERK1/2 activation.
Many healthcare workers were infected by coronavirus disease 2019 (COVID-19) early in the epidemic posing a big challenge for epidemic control. Hence, this study aims to explore perceived infection ...routes, influencing factors, psychosocial changes, and management procedures for COVID-19 infected healthcare workers.
This is a cross-sectional, single hospital-based study. We recruited all 105 confirmed COVID-19 healthcare workers in the Zhongnan Hospital of Wuhan University from February 15 to 29, 2020. All participants completed a validated questionnaire. Electronic consent was obtained from all participants. Perceived causes of infection, infection prevention, control knowledge and behaviour, psychological changes, symptoms and treatment were measured.
Finally, 103 professional staff with COVID-19 finished the questionnaire and was included (response rate: 98.1%). Of them, 87 cases (84.5%) thought they were infected in working environment in hospital, one (1.0%) thought their infection was due to the laboratory environment, and 5 (4.9%) thought they were infected in daily life or community environment. Swab of throat collection and physical examination were the procedures perceived as most likely causing their infection by nurses and doctors respectively. Forty-three (41.8%) thought their infection was related to protective equipment, utilization of common equipment (masks and gloves). The top three first symptoms displayed before diagnosis were fever (41.8%), lethargy (33.0%) and muscle aches (30.1%). After diagnosis, 88.3% staff experienced psychological stress or emotional changes during their isolation period, only 11.7% had almost no emotional changes. Arbidol (Umifenovir; an anti-influza drug; 69.2%) was the drug most commonly used to target infection in mild and moderate symptoms.
The main perceived mode of transmission was not maintaining protection when working at a close distance and having intimate contact with infected cases. Positive psychological intervention is necessary.
Backgrounds/Aims: Epithelial-to-mesenchymal transition (EMT) has been proven to be involved in development and progression of pulmonary fibrosis. This study aims to investigate the role of ...transforming growth factor β1 (TGFβ1)-smad signaling pathway in the interleukin-33 (IL-33) induced EMT. Methods: The human type II alveolar epithelial cell line, A549, and small airway epithelial cells (SAEC) were cultured and divided into 4 groups including Control, LY-2109761 (TGFβ receptor inhibitor), IL-33 and IL-33+LY-2109761 group. Expression of TGFβ1, E-cadherin (E-cad) and α-smooth muscle actin (α-SMA) were examined by using real-time PCR (RT-PCR) and western blot assay, respectively. The smad3 signaling pathway factors, including smad3 and phosphorylated smad3 (p-smad3), were also detected by using western blot assay. Results: IL-33 significantly activated T1/ST2 expression in A549 cells (P< 0.05). TGFβ1 receptor inhibitor significantly suppressed the IL-33 caused down-expression of E-cad compared to IL-33 alone (P< 0.05). IL-33 significantly increased the α-SMA levels compared to Control group (P< 0.05) and TGFβ1 receptor inhibitor inhibited the other effects of IL-33. IL-33 significantly enhanced the levels of TGFβ1 compared to Control group (P< 0.05). TGFβ1 receptor inhibitor suppressed the IL-33 induced up-expression of p-smad3. Conclusion: The TGFβ1-smad signaling pathway participates in the IL-33 induced epithelial-to-mesenchymal transition of A549 cells.
The natural products, metabolites, of gut microbes are crucial effect factors on diseases. Comprehensive identification and annotation of relationships among disease, metabolites, and microbes can ...provide efficient and targeted solutions towards understanding the mechanism of complex disease and development of new markers and drugs. We developed Gut Microbial Metabolite Association with Disease (GMMAD), a manually curated database of associations among human diseases, gut microbes, and metabolites of gut microbes. Here, this initial release (i) contains 3,836 disease-microbe associations and 879,263 microbe-metabolite associations, which were extracted from literatures and available resources and then experienced our manual curation; (ii) defines an association strength score and a confidence score. With these two scores, GMMAD predicted 220,690 disease-metabolite associations, where the metabolites all belong to the gut microbes. We think that the positive effective (with both scores higher than suggested thresholds) associations will help identify disease marker and understand the pathogenic mechanism from the sense of gut microbes. The negative effective associations would be taken as biomarkers and have the potential as drug candidates. Literature proofs supported our proposal with experimental consistence; (iii) provides a user-friendly web interface that allows users to browse, search, and download information on associations among diseases, metabolites, and microbes. The resource is freely available at http://guolab.whu.edu.cn/GMMAD. As the online-available unique resource for gut microbial metabolite-disease associations, GMMAD is helpful for researchers to explore mechanisms of disease- metabolite-microbe and screen the drug and marker candidates for different diseases.
Calpains are intracellular calcium-dependent cysteine proteases, which cleave several substrates proteins, have been proven to play important roles in lung fibrosis. The aim of this study was to ...investigate the effects of calpain on bleomycin (BLM)-induced pulmonary fibrosis. A lung fibrosis mice model was established successfully by intraperitoneal injection of bleomycin. Calpeptin, a highly selective inhibitor of calpain activation, was administered three times weekly after bleomycin injection. Histological examination was used to assess the fibrosis. Quantitative-PCR and Western blotting were used to assess the development of epithelial-mesenchymal transition (EMT). We found calpeptin treatment decreased the BLM-induced EMT-associated markers, such as muscle actin (α-SMA) and collagen-I, while increased E-cadherin (E-cad). Calpeptin also suppressed the activation of transforming growth factor β1 (TGFβ1)-Smad2/3 signaling pathway, which plays crucial role in lung fibrosis and EMT. Furthermore, we found differentiated embryonic chondrocyte-expressed gene 1 (DEC1), an important transcription factor, was upregulated in both patients with idiopathic pulmonary fibrosis and in bleomycin-induced lung fibrosis. DEC1 was suppressed by calpeptin in bleomycin-induced mice model. Collectively, these findings indicated that calpeptin had a potential anti-fibrosis effect, which focus on the development of EMT.
...current evidence and clinical guideline10 do not recommend NPPV for treating acute hypoxic respiratory failure and pandemic viral illness. ...we believe that NPPV should currently not be used as a ...first-line treatment to correct respiratory failure in patients with COVID-19 pneumonia. ...early-stage identification of high-risk factors (shock, metabolic acidosis; multiple organ failure; PaO2/FiO2 ≤175 mmHg at 1 h after NPPV treatment; severe hypoxemia with PaO2/FiO2 ≤147 mmHg; Simplified Acute Physiology Score II >34; tidal volume >9.5 mL/kg; elevated partial pressure of arterial carbon dioxide (PaCO2); respiratory rate >30 breaths/min) for NPPV failure in the treatment of hypoxic respiratory failure can improve the safety of NPPV treatment. 18 Nosocomial Infection Prevention and Control During HFNC Therapy To prevent and control the nosocomial infection during HFNC therapy, we provide the following suggestions based on our experience: (1) disposable, single-use high-flow nasal plugs and tubing should be used during HFNC treatment; (2) patients should be instructed to breathe with the mouth closed as much as possible while wearing surgical masks or oxygen mask; (3) condensation in the circuit should be cleaned in a timely manner to avoid production of aerosols caused by high flow gas and condensed water entering the nasal cavity, stimulating coughing in patients; (4) recent evidence shows that the dispersion distance of exhaled gases during HFNC treatment is limited, and the risk of airborne transmission is low.
...Tan et al4 revealed that lymphopenia could happen to moderately, severely, and critically ill COVID-19 patients in the initial stage of disease. Lymphocytes increased later in recovery patients, ...whereas, continued to decrease in dead patients. ...it is the lymphocyte-time curve that is important for prognosis prediction. ...viral loads (Ct values) were not recorded in our study. ...viral clearance occurred after temperature recovery in a significant proportion of COVID-19 patients.
There are two minimally invasive ways of treating cholecystolithiasis combined with choledocholithiasis, but there remains some controversy regarding which technique is better, since they both have ...advantages and disadvantages. The one-step method involves laparoscopic cholecystectomy, laparoscopic common bile duct exploration, and primary close (LC + LCBDE + PC), while the two-step procedure consists of endoscopic retrograde cholangiopancreatography, endoscopic sphincterotomy, and laparoscopic cholecystectomy (ERCP + EST + LC).
This multicenter retrospective study aimed to analyze and compare the effects of the two techniques.
The data of patients who underwent either one-step LCBDE + LC + PC or two-step ERCP + EST + LC treatment for gallstones in the gallbladder and bile duct at the Shanghai Tenth People's Hospital, Shanghai Tongren Hospital, and Taizhou Fourth People's Hospital between January 1, 2015 and December 31, 2019 were collected, and the preoperative indicators of the two groups were compared.
The surgical success rate of the one-step laparoscopic group was 96.23% (664/690), the transit abdominal opening rate was 2.03% (14/690), and there were 21 cases of postoperative bile leakage. The success rate of the two-step endolaparoscopic surgery was 78.95% (225/285), the transit opening rate was 2.46% (7/285), and there were 43 postoperative cases of pancreatitis and five of cholangitis. Postoperative cholangitis, pancreatitis, postoperative stone recurrence, postoperative hospitalization, and treatment costs were significantly lower (P< 0.05) in the one-step laparoscopic group than in the two-step endolaparoscopic group. However, the amount of intraoperative bleeding, the postoperative extraction time of the abdominal drainage tube, and the incidence of bile leakage were higher (P< 0.05) in the one-step laparoscopic group than in the two-step endolaparoscopic group.
The two methods of treating choledocholithiasis combined with choledocholithiasis that were analyzed in this study were safe and effective, and each method had its own advantages.
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