Searching therapeutic strategy of new coronavirus pneumonia from angiotensin-converting enzyme 2: the target of COVID-19 and SARS-CoV.
从血管紧张素转换酶 2 寻找新型冠状病毒肺炎的治疗策略: 新型冠状病毒肺炎传染性非典型肺炎-CoV的靶点。
- 作者列表："Li SR","Tang ZJ","Li ZH","Liu X
:Since December 2019, the infection of the new coronavirus (COVID-19) caused an outbreak of new coronavirus pneumonia in Wuhan, China, and caused great public concern. Both COVID-19 and SARS-CoV belong to the coronavirus family and both invade target cells through ACE2. An in-depth understanding of ACE2 and a series of physiological and physiological changes caused by the virus invading the human body may help to discover and explain the corresponding clinical phenomena and then deal with them timely. In addition, ACE2 is a potential therapeutic target. This article will summarize the role of ACE2 in multiple organ damage caused by COVID-19 and SARS-CoV, targeted blocking drugs against ACE2, and drugs that inhibit inflammation in order to provide the basis for subsequent related research, diagnosis and treatment, and drug development.
: 2019 年 12 月以来，新型冠状病毒 (新型冠状病毒肺炎) 感染引起中国武汉新型冠状病毒肺炎疫情，引起公众极大关注。两个新型冠状病毒肺炎和传染性非典型肺炎-CoV同属冠状病毒家族都侵入靶细胞通过ACE2.深入了解ACE2 以及病毒侵入人体后引起的一系列生理、生理变化，可能有助于发现和解释相应的临床现象，进而及时处理。此外，ACE2 是潜在的治疗靶点。本文将总结作用ACE2 在所致多脏器损害的新型冠状病毒肺炎和传染性非典型肺炎-CoV，靶向阻断药物ACE2，和抑制炎症的药物，以便为后续的相关研究、诊断和治疗以及药物开发提供依据。
METHODS::The antimicrobial functions of neutrophils are facilitated by a defensive armamentarium of proteins stored in granules, and by the formation of neutrophil extracellular traps (NETs). However, the toxic nature of these structures poses a threat to highly vascularized tissues, such as the lungs. Here, we identified a cell-intrinsic program that modified the neutrophil proteome in the circulation and caused the progressive loss of granule content and reduction of the NET-forming capacity. This program was driven by the receptor CXCR2 and by regulators of circadian cycles. As a consequence, lungs were protected from inflammatory injury at times of day or in mouse mutants in which granule content was low. Changes in the proteome, granule content and NET formation also occurred in human neutrophils, and correlated with the incidence and severity of respiratory distress in pneumonia patients. Our findings unveil a 'disarming' strategy of neutrophils that depletes protein stores to reduce the magnitude of inflammation.
METHODS::Pneumonia is a common respiratory infectious disease that involves the inflammation of the pulmonary parenchyma. Periodontal disease is widespread and correlated with pneumonia. However, the relationship between periodontal treatment and clinical infectious outcomes in patients with pneumonia has remained undetermined. The aim of this study was to investigate the association between periodontal treatment and the risk of pneumonia events in the Taiwanese population. A nationwide population-based cohort study was conducted using data from the Taiwanese National Health Insurance Research Database (NHIRD). A total of 49,400 chronic periodontitis patients who received periodontal treatment from 2001 to 2012 were selected. In addition, 49,400 healthy individuals without periodontal diseases were picked randomly from the general population after propensity score matching according to age, gender, monthly income, urbanization, and comorbidities. The Cox proportional hazard regression analysis was adopted to assess the hazard ratio (HR) of pneumonia between the periodontal treatment cohort and the comparison cohort. The average ages of the periodontal treatment and comparison groups were 44.25 ± 14.82 years and 44.15 ± 14.5 years, respectively. The follow up durations were 7.66 and 7.41 years for the periodontal treatment and comparison groups, respectively. We found 2504 and 1922 patients with newly diagnosed pneumonia in the comparison cohort and the periodontal treatment cohort, respectively. The Kaplan-Meier plot revealed that the cumulative incidence of pneumonia was significantly lower over the 12 year follow-up period in the periodontal treatment group (using the log-rank test, p < 0.001). In conclusion, this nationwide population-based study indicated that the patients with periodontal treatment exhibited a significantly lower risk of pneumonia than the general population.
METHODS:OBJECTIVE:To describe the treatment of community-acquired pneumonia (CAP) in children under five years in Tanzania. METHODS:Between January and December 2017, children aged 2-59 months with chest radiography-confirmed CAP were enrolled. The parents were interviewed to collect information on the patients and home-based medication. Clinical information was derived from the patient files. Nasopharyngeal swab and blood samples were collected for isolation of the causative pathogens. Swab samples were analysed by quantitative PCR whereas blood samples were tested using BacT/Alert 3D. RESULTS:Overall, 109 children with CAP were included in this analysis. Provision of care to most children was delayed (median = 4.6 days). A quarter (26.6%) were given unprescribed/leftover antibiotics at home. Only one child had positive bacterial culture. Referrals were associated with nasopharyngeal carriage of Streptococcus pneumoniae (p = 0.003) and Haemophilus influenzae (p = 0.004). Of all admitted children, more than a quarter (n = 29) did not need to be hospitalised and inappropriately received injectable instead of oral antibiotics. CONCLUSION:We found high rates of home treatment, particularly with antibiotics. Appropriate health care was delayed for most children because of home treatment. Efforts are needed at the community level to improve awareness of antimicrobial resistance.