An ongoing outbreak of 2019-nCoV pneumonia was first identified in Wuhan, Hubei province, China at the end of 2019. With the spread of the new coronavirus accelerating, person-to-person transmission ...in family homes or hospitals, and intercity spread of 2019-nCoV occurred. At least 40,261 cases confirmed, 23,589 cases suspected, 909 cases death and 3444 cases cured in China and worldwide 24 countries confirmed 383 cases being diagnosed, 1 case death in February 10th, 2020. At present, the mortality of 2019-nCoV in China is 2.3%, compared with 9.6% of SARS and 34.4% of MERS reported by WHO. It seems the new virus is not as fatal as many people thought. Chinese authorities improved surveillance network, made the laboratory be able to recognize the outbreak within a few weeks and announced the virus genome that provide efficient epidemiological control. More comprehensive information is required to understand 2019-nCoV feature, the epidemiology of origin and spreading, and the clinical phenomina. According to the current status, blocking transmission, isolation, protection, and alternative medication are the urgent management strategies against 2019-nCoV.
Tumor neoantigen is the truly foreign protein and entirely absent from normal human organs/tissues. It could be specifically recognized by neoantigen-specific T cell receptors (TCRs) in the context ...of major histocompatibility complexes (MHCs) molecules. Emerging evidence has suggested that neoantigens play a critical role in tumor-specific T cell-mediated antitumor immune response and successful cancer immunotherapies. From a theoretical perspective, neoantigen is an ideal immunotherapy target because they are distinguished from germline and could be recognized as non-self by the host immune system. Neoantigen-based therapeutic personalized vaccines and adoptive T cell transfer have shown promising preliminary results. Furthermore, recent studies suggested the significant role of neoantigen in immune escape, immunoediting, and sensitivity to immune checkpoint inhibitors. In this review, we systematically summarize the recent advances of understanding and identification of tumor-specific neoantigens and its role on current cancer immunotherapies. We also discuss the ongoing development of strategies based on neoantigens and its future clinical applications.
Mesenchymal stem cells secrete paracrine factors that can regulate lung permeability and decrease inflammation, making it a potentially attractive therapy for acute lung injury. However, concerns ...exist whether mesenchymal stem cells' immunomodulatory properties may have detrimental effects if targeted toward infectious causes of lung injury.
Therefore, we tested the effect of mesenchymal stem cells on lung fluid balance, acute inflammation, and bacterial clearance.
We developed an Escherichia coli pneumonia model in our ex vivo perfused human lung to test the therapeutic effects of mesenchymal stem cells on bacterial-induced acute lung injury.
Clinical-grade human mesenchymal stem cells restored alveolar fluid clearance to a normal level, decreased inflammation, and were associated with increased bacterial killing and reduced bacteremia, in part through increased alveolar macrophage phagocytosis and secretion of antimicrobial factors. Keratinocyte growth factor, a soluble factor secreted by mesenchymal stem cells, duplicated most of the antimicrobial effects. In subsequent in vitro studies, we discovered that human monocytes expressed the keratinocyte growth factor receptor, and that keratinocyte growth factor decreased apoptosis of human monocytes through AKT phosphorylation, an effect that increased bacterial clearance. Inhibition of keratinocyte growth factor by a neutralizing antibody reduced the antimicrobial effects of mesenchymal stem cells in the ex vivo perfused human lung and monocytes grown in vitro injured with E. coli bacteria.
In E. coli-injured human lungs, mesenchymal stem cells restored alveolar fluid clearance, reduced inflammation, and exerted antimicrobial activity, in part through keratinocyte growth factor secretion.
Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection is spreading globally and poses a huge threat to human health. Besides ...common respiratory symptoms, some patients with COVID-19 experience gastrointestinal symptoms, such as diarrhea, nausea, vomiting, and loss of appetite. SARS-CoV-2 might infect the gastrointestinal tract through its viral receptor angiotensin-converting enzyme 2 (ACE2) and there is increasing evidence of a possible fecal-oral transmission route. In addition, there exist multiple abnormalities in liver enzymes. COVID-19-related liver injury may be due to drug-induced liver injury, systemic inflammatory reaction, and hypoxia-ischemia reperfusion injury. The direct toxic attack of SARS-CoV-2 on the liver is still questionable. This review highlights the manifestations and potential mechanisms of gastrointestinal and hepatic injuries in COVID-19 to raise awareness of digestive system injury in COVID-19.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which are characterized by excessive inflammation and accompanied by diffuse injury of alveoli, can result in severe ...respiratory failures. The morbidity and mortality of patients remain high because the major treatments for ALI/ARDS are mainly supportive due to the lack of effective therapies. Numerous studies have demonstrated that the aggravation of coronavirus disease 2019 (COVID-19) leads to severe pneumonia and even ARDS. Pyroptosis, a biological process identified as a type of programed cell death, is mainly triggered by inflammatory caspase activation and is directly meditated by the gasdermin protein family, as well as being associated with the secretion and release of pro-inflammatory cytokines. Clinical and experimental evidence corroborates that pyroptosis of various cells in the lung, such as immune cells and structural cells, may play an important role in the pathogenesis of "cytokine storms" in ALI/ARDS, including those induced by COVID-19. Here, with a focus on ALI/ARDS and COVID-19, we summarized the recent advances in this field and proposed the theory of an inflammatory cascade in pyroptosis to identify new targets and pave the way for new approaches to treat these diseases.
Home noninvasive positive pressure ventilation (NIPPV) has become evidence-based care for stable hypercapnic chronic obstructive pulmonary disease (COPD) patients. There are still other challenges ...including appropriate follow-up, telemonitor, and management to ensure treatment effectiveness, compliance, and security and to improve quality of life. The Internet of things (IOT) is the name given to the network of devices and other "things" with built-in sensors, software, electronics, and network connectivity, communicating these objects over wireless networks and sending data to a cloud platform. The study aims to evaluate the effectiveness and safety of the IOT-based management of NIPPV for the COPD patients with hypercapnic chronic respiratory failure.
This multicenter, prospective, randomized controlled trial was conducted with a total of 200 COPD patients with chronic hypercapnic respiratory failure. Using a computer-generated randomization process, patients were randomized (in a 1:1 ratio) into the usual NIPPV (control group) or to receive additional IOT-based management (intervention group) for 12 months. The primary outcome was the Severe Respiratory Insufficiency (SRI) questionnaire. Secondary outcomes included compliance with the ventilator, gas exchange, lung function, health-related quality of life, hospitalization frequency, time to death within 1-year, all-cause mortality, safety analysis, and cost-effectiveness analysis.
This study will be the first and largest randomized trial in China to evaluate the effectiveness and safety of the IOT-based management of NIPPV for COPD patients with chronic hypercapnic respiratory failure. The results will help to understand the current situation of IOT-based home ventilation and may provide new evidence for home NIPPV treatment and management in the future.
Chinese Clinical Trials Registry ChiCTR1800019536 . Registered on 17 November 2018.
Recent in vivo studies indicate that mesenchymal stem cells (MSCs) may have beneficial effects in the treatment of sepsis induced by bacterial infection. Administration of MSCs in these studies ...improved survival and enhanced bacterial clearance. The primary objective of this study was to test the hypothesis that human MSCs possessed intrinsic antimicrobial properties. We studied the effect of human MSCs derived from bone marrow on the bacterial growth of Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. MSCs as well as their conditioned medium (CM) demonstrated marked inhibition of bacterial growth in comparison with control medium or normal human lung fibroblasts (NHLF). Analysis of expression of major antimicrobial peptides indicated that one of the factors responsible for the antimicrobial activity of MSC CM against Gram-negative bacteria was the human cathelicidin antimicrobial peptide, hCAP-18/LL-37. Both m-RNA and protein expression data showed that the expression of LL-37 in MSCs increased after bacterial challenge. Using an in vivo mouse model of E. coli pneumonia, intratracheal administration of MSCs reduced bacterial growth (in colony-forming unit) in the lung homogenates and in the bronchoalveolar lavage (BAL) fluid, and administration of MSCs simultaneously with a neutralizing antibody to LL-37 resulted in a decrease in bacterial clearance. In addition, the BAL itself from MSC-treated mice had a greater antimicrobial activity in comparison with the BAL of phosphate buffered saline (PBS)-treated mice. Human bone marrow-derived MSCs possess direct antimicrobial activity, which is mediated in part by the secretion of human cathelicidin hCAP-18/ LL-37.
Circular RNAs (CircRNAs), as a new class of non-coding RNA molecules that, unlike linear RNAs, have covalently closed loop structures from the ligation of exons, introns, or both. CircRNAs are widely ...expressed in various organisms in a specie-, tissue-, disease- and developmental stage-specific manner, and have been demonstrated to play a vital role in the pathogenesis and progression of human diseases. An increasing number of recent studies has revealed that circRNAs are intensively associated with different respiratory diseases, including lung cancer, acute respiratory distress syndrome, pulmonary hypertension, pulmonary tuberculosis, and silicosis. However, to the best of our knowledge, there has been no systematic review of studies on the role of circRNAs in respiratory diseases. In this review, we elaborate on the biogenesis, functions, and identification of circRNAs and focus particularly on the potential implications of circRNAs in respiratory diseases.
Although exposure to cigarette smoking and air pollution is common, the current prevalence of chronic obstructive pulmonary disease (COPD) is unknown in the Chinese adult population. We conducted the ...China Pulmonary Health (CPH) study to assess the prevalence and risk factors of COPD in China.
The CPH study is a cross-sectional study in a nationally representative sample of adults aged 20 years or older from ten provinces, autonomous regions, and municipalities in mainland China. All participants underwent a post-bronchodilator pulmonary function test. COPD was diagnosed according to 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.
Between June, 2012, and May, 2015, 57 779 individuals were invited to participate, of whom 50 991 (21 446 men and 29 545 women) had reliable post-bronchodilator results and were included in the final analysis. The overall prevalence of spirometry-defined COPD was 8·6% (95% CI 7·5–9·9), accounting for 99·9 (95% CI 76·3–135·7) million people with COPD in China. Prevalence was higher in men (11·9%, 95% CI 10·2–13·8) than in women (5·4%, 4·6–6·2; p<0·0001 for sex difference) and in people aged 40 years or older (13·7%, 12·1–15·5) than in those aged 20–39 years (2·1%, 1·4–3·2; p<0·0001 for age difference). Only 12·0% (95% CI 8·1–17·4) of people with COPD reported a previous pulmonary function test. Risk factors for COPD included smoking exposure of 20 pack-years or more (odds ratio OR 1·95, 95% CI 1·53–2·47), exposure to annual mean particulate matter with a diameter less than 2·5 μm of 50–74 μg/m3 (1·85, 1·23–2·77) or 75 μg/m3 or higher (2·00, 1·36–2·92), underweight (body-mass index <18·5 kg/m2; 1·43, 1·03–1·97), sometimes childhood chronic cough (1·48, 1·14–1·93) or frequent cough (2·57, 2·01–3·29), and parental history of respiratory diseases (1·40, 1·23–1·60). A lower risk of COPD was associated with middle or high school education (OR 0·76, 95% CI 0·64–0·90) and college or higher education (0·47, 0·33–0·66).
Spirometry-defined COPD is highly prevalent in the Chinese adult population. Cigarette smoking, ambient air pollution, underweight, childhood chronic cough, parental history of respiratory diseases, and low education are major risk factors for COPD. Prevention and early detection of COPD using spirometry should be a public health priority in China to reduce COPD-related morbidity and mortality.
Ministry of Health and Ministry of Science and Technology of China.
Despite substantial progress in reducing the global impact of many non-communicable diseases, including heart disease and cancer, morbidity and mortality due to chronic respiratory disease continues ...to increase. Many factors have contributed to what must now be considered a public health emergency: failure to limit the sale and consumption of tobacco products, unchecked exposure to environmental pollutants across the life course, and the ageing of the global population (partly as a result of improved outcomes for other conditions). In particular, we advocate for: broader understanding of risk factors (including the devastating effects of global poverty) and the preventive measures necessary to avoid future cases of COPD, disruptive approaches to diagnosis that are not solely based on spirometric airflow limitation but also involve identification of early pathological changes that are more amenable to reversal, classification of the disease into types that share pathophysiological similarities and could lead to novel preventive and therapeutic approaches, and a new approach to the diagnosis and assessment of exacerbations of COPD that focuses on disease mechanisms. An acute worsening of COPD is termed an exacerbation, and such episodes account for a substantial proportion of the attributable cost of the disease and are associated with accelerated lung function loss, prolonged impairments in quality of life, and similar prognosis to many stage III or IV solid organ malignancies.
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