Neutrophil elastase:From mechanisms to therapeutic potential

Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammatory process.NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling.However,NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction.Additionally,it plays a complex role in various physiological processes and mediates several diseases.Sivelestat,a specific NE inhibitor,has strong potential for clinical application,particularly in the treatment of coronavirus disease 2019(COVID-19).This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.

Ambient Temperature and Years of Life Lost:A National Study in China

Although numerous studies have investigated premature deaths attributable to temperature,effects of temperature on years of life lost(YLL)remain unclear.We estimated the relationship between temperatures and YLL,and quantified the YLL per death caused by temperature in China.We collected daily meteorological and mortality data,and calculated the daily YLL values for 364 locations(2013–2017 in Yunnan,Guangdong,Hunan,Zhejiang,and Jilin provinces,and 2006–2011 in other locations)in China.A time-series design with a distributed lag nonlinear model was first employed to estimate the location-specific associations between temperature and YLL rates(YLL/100,000 population),and a multivariate meta-analysis model was used to pool location-specific associations.Then,YLL per death caused by temperatures was calculated.The temperature and YLL rates consistently showed U-shaped associations.A mean of 1.02(95%confidence interval:0.67,1.37)YLL per death was attributable to temperature.Cold temperature caused 0.98 YLL per death with most from moderate cold(0.84).The mean YLL per death was higher in those with cardiovascular diseases(1.14),males(1.15),younger age categories(1.31 in people aged 65–74 years),and in central China(1.34)than in those with respiratory diseases(0.47),females(0.87),older people(0.85 in people R75 years old),and northern China(0.64)or southern China(1.19).The mortality burden was modified by annual temperature and temperature variability,relative humidity,latitude,longitude,altitude,education attainment,and central heating use.Temperatures caused substantial YLL per death in China,which was modified by demographic and regional characteristics.

When and How to Adjust Non-Pharmacological Interventions Concurrent with Booster Vaccinations Against COVID-19—Guangdong,China,2022

Introduction:With the large-scale roll-out of the coronavirus disease 2019(COVID-19)booster vaccination effort(a vaccine dose given 6 months after completing primary vaccination)in China,we explore when and how China could lift non-pharmacological interventions(NPIs)against COVID-19 in 2022.Methods:Using a modified susceptible-infectiousrecovered(SIR)mathematical model,we projected the COVID-19 epidemic situation and required medical resources in Guangdong Province,China.Results:If the number of people entering from overseas recovers to 20%of the number in 2019,the epidemic in 2022 could be controlled at a low level by a containment(215 local cases)or suppression strategy(1,397 local cases).A mitigation strategy would lead to 21,722 local cases.A coexistence strategy would lead to a large epidemic with 6,850,083 local cases that would overwhelm Guangdong’s medical system.With 50%or 100%recovery of the 2019 level of travelers from overseas,the epidemic could also be controlled with containment or suppression,but enormous resources,including more hotel rooms for border quarantine,will be required.However,coexistence would lead to an uncontrollable epidemic with 12,922,032 local cases.Discussion:With booster vaccinations,the number of travelers from overseas could increase slightly in 2022,but a suppression strategy would need to be maintained to ensure a controllable epidemic.