Platelets in hemostasis and thrombosis:Novel mechanisms of fibrinogen-independent platelet aggregation and fibronectin-mediated protein wave of hemostasis

Platelets are small anucleate cells generated from megakaryocytes in the bone marrow.Although platelet generation,maturation,and clearance are still not fully understood,significant progress has been made in the last 1-2 decades.In blood circulation,platelets can quickly adhere and aggregate at sites of vascular injury,forming the platelet plug(i.e.the first wave of hemostasis).Activated platelets can also provide negatively charged phosphatidylserinerich membrane surface that enhances cell-based thrombin generation,which facilitates blood coagulation(i.e.the second wave of hemostasis).Platelets therefore play central roles in hemostasis.However,the same process of hemostasis may also cause thrombosis and vessel occlusion,which are the most common mechanisms leading to heart attack and stroke following ruptured atherosclerotic lesions.In this review,we will introduce the classical mechanisms and newly discovered pathways of platelets in hemostasis and thrombosis,including fibrinogen-independent platelet aggregation and thrombosis,and the plasma fibronectin-mediated "protein wave" of hemostasis that precedes the classical first wave of hemostasis.Furthermore,we briefly discuss the roles of platelets in inflammation and atherosclerosis and the potential strategies to control atherothrombosis.

Cumulative Risk Assessment of Exposure to Heavy Metals through Aquatic Products in China

Objective This study aimed to assess the risk of cumulative exposure to Pb,Cd,Hg,and iAs through aquatic products consumed by Chinese people.Methods Heavy metal concentration data were obtained from the national food contamination monitoring program during 2013–2017.Consumption data were derived from the China National Food Consumption Survey in 2014 and the relative potency factor(RPF)method was used to estimate cumulative exposure for neurotoxicity and nephrotoxicity.Results The results demonstrated that the cumulative exposure based on neurotoxicity was below the lower confidence limit on benchmark doses of lead(BMDL01)for nephrotoxicity and the cumulative exposures were all lower than the provisional tolerable monthly intake(PTMI)of Cd.However,the margin of exposure values(MOEs)of the cumulative exposures for neurotoxicity in the 2–6 year-old group was close to 1 and the cumulative exposure level for nephrotoxicity accounted for 90.21%of the PTMI.Conclusion The cumulative exposures of the 2–6 year-old group to the four heavy metals did not reach(but came close to)the corresponding safety threshold for both neurotoxicity and nephrotoxicity.Given that there are still other food sources of these four heavy metals,it is necessary to more closely study their cumulative health effects.

Serological Investigation of Laboratory-Confirmed and Suspected Ebola Virus Disease Patients During the Late Phase of the Ebola Outbreak in Sierra Leone

This study aimed to investigate the serological characteristics of Ebola virus(EBOV) infection during the late phase of the Ebola outbreak in Sierra Leone. In total, 877 blood samples from 694 suspected Ebola virus disease(EVD) cases assessed from March to December 2015, were analyzed via real-time reverse transcription polymerase chain reaction(RT-PCR) for viral RNA and enzyme-linked immunosorbent assay(ELISA) and Luminex to detect antibodies against EBOV. Viral load and EBOV-specific IgM/IgG titers displayed a declining trend during March to December 2015. Viral RNA load decreased rapidly at earlier stages after disease onset, while EBOV-specific IgM and IgG still persisted in 58.1%(18/31) and 93.5%(29/31) of the confirmed EVD patients and in 3.8%(25/663) and 17.8%(118/663) of the RNA-negative suspected patients in the later phase, respectively. Dynamic analysis of longitudinally collected samples from eight EVD patients revealed typically reversed trends of declining viral load and increasing IgM and/or IgG titers in response to the EBOV infection.The present results indicate that certain populations of Sierra Leone developed immunity to an EBOV infection in the late phase of the outbreak, providing novel insights into the risk assessment of EBOV infections among human populations.

Effectiveness of Interventions to Control Transmission of Reemergent Cases of COVID-19--Jilin Province,China,2020

What is already known about this topic?COVID-19 has a high transmissibility calculated by mathematical model.The dynamics of the disease and the effectiveness of intervention to control the transmission remain unclear in Jilin Province,China.What is added by this report?This is the first study to report the dynamic characteristics and to quantify the effectiveness of interventions implemented in the second outbreak of COVID-19 in Jilin Province,China.The effective reproduction number of the disease before and after May 10 was 4.00 and p<0.01,respectively.The combined interventions reduced the transmissibility of COVID-19 by 99% and the number of cases by 98.36%.What are the implications for public health practice?The findings of this study would add data on the transmission of COVID-19 and provide evidence to prepare the second outbreak transmission of the disease in other areas of China even in many other countries.

Transmissibility of tuberculosis among students and non-students:an occupational-specific mathematical modelling

Background: Recently, despite the steady decline in the tuberculosis (TB) epidemic globally, school TB outbreaks have been frequently reported in China. This study aimed to quantify the transmissibility ofMycobacterium tuberculosis (MTB) among students and non-students using a mathematical model to determine characteristics of TB transmission.Methods: We constructed a dataset of reported TB cases from four regions (Jilin Province, Xiamen City, Chuxiong Prefecture, and Wuhan City) in China from 2005 to 2019. We classified the population and the reported cases under student and non-student groups, and developed two mathematical models [nonseasonal model (Model A) and seasonal model (Model B)] based on the natural history and transmission features of TB. The effective reproduction number (R(eff)) of TB between groups were calculated using the collected data.Results: During the study period, data on 456,423 TB cases were collected from four regions: students accounted for 6.1% of cases. The goodness-of-fit analysis showed that Model A had a better fitting effect (P < 0.001). The average R_(eff) of TB estimated from Model A was 1.68 [interquartile range (IQR): 1.20–1.96] in Chuxiong Prefecture, 1.67 (IQR: 1.40–1.93) in Xiamen City, 1.75 (IQR: 1.37–2.02) in Jilin Province, and 1.79 (IQR: 1.56–2.02) in Wuhan City. The average R_(eff) of TB in the non-student population was 23.30 times (1.65/0.07) higher than that in the student population.Conclusions: The transmissibility of MTB remains high in the non-student population of the areas studied, which is still dominant in the spread of TB. TB transmissibility from the non-student-to-student-population had a strong influence on students. Specific interventions, such as TB screening, should be applied rigorously to control and to prevent TB transmission among students.

HIV-Related Knowledge, Attitude, and Practices Research Among College Students-Six Chinese Cities, 2021

Summary What is already known about this topic?The number of newly diagnosed human immunodeficiency virus(HIV)cases among Chinese youth 15–24 years of age shows an upward trend between 2010 and 2019.What is added by this report?This survey is on a larger scale as compared to previous studies.It shows inadequate HIV knowledge—especially on HIV treatment,self-testing,and postexposure prophylaxis—among college students.A significant gap exists between knowledge and behavior as indicated by the low condom use rate despite a high knowledge level.

The Initial Case of COVID-19—Shulan City,Jilin Province,China,May 8,2020

Coronavirus disease 2019(COVID-19)was designated a global pandemic by the World Health Organization(WHO)on March 11,2020(1).After great effort,COVID-19 has been well-controlled in China,but new challenges have emerged due to increasing numbers of imported cases from outside of China.On May 8,the Health Commission of Jilin Province reported a confirmed COVID-19 case of a 45-year-old laundry woman from Shulan City in the northeast of China.This case was suspected to be associated with a possible importation event.

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.

A five-compartment model of age-specific transmissibility of SARS-CoV-2

Background:The novel coronavirus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2,also called 2019-nCoV)causes different morbidity risks to individuals in different age groups.This study attempts to quantify the age-specific transmissibility using a mathematical model.Methods:An epidemiological model with five compartments(susceptible-exposed-symptomatic-asymptomatic-recovered/removed[SEIAR])was developed based on observed transmission features.Coronavirus disease 2019(COVID-19)cases were divided into four age groups:group 1,those≤14years old;group 2,those 15 to 44years old;group 3,those 45 to 64years old;and group 4,those≥65 years old.The model was initially based on cases(including imported cases and secondary cases)collected in Hunan Province from January 5 to February 19,2020.Another dataset,from Jilin Province,was used to test the model.Results:The age-specific SEIAR model fitted the data well in each age group(P<0.001).In Hunan Province,the highest transmissibility was from age group 4 to 3(median:β43=7.71×10-9;SAR43=3.86×10-8),followed by group 3 to 4(median:β34=3.07×10-9;SAR34=1.53×10-8),group 2 to 2(median:β22=1.24×10-9;SAR22=6.21×10-9),and group 3 to 1(median:β31=4.10×10-10;SAR31=2.08×10-9).The lowest transmissibility was from age group 3 to 3(median:β33=1.64×10-19;SAR33=8.19×10-19),followed by group 4 to 4(median:β44=3.66×10-17;SAR44=1.83×10-16),group 3 to 2(median:β32=1.21×10-16;SAR32=6.06×10-16),and group 1 to 4(median:β14=7.20×10-14;SAR14=3.60×10-13).In Jilin Province,the highest transmissibility occurred from age group 4 to 4(median:β43=4.27×10-8;SAR43=2.13×10-7),followed by group 3 to 4(median:β34=1.81×10-8;SAR34=9.03×10-8).Conclusions:SARS-CoV-2 exhibits high transmissibility between middle-aged(45 to 64 years old)and elderly(≥65 years old)people.Children(≤14 years old)have very low susceptibility to COVID-19.This study will improve our understanding of the transmission feature of SARS-CoV-2 in different age groups and suggest the most prevention measures should be applied to middle-aged and elderly people.

The substitution V379I in PA protein attenuates the pathogenicity of influenza A(H1N1)pdm09 viruses in mice

Dear Editor,Since August 2010,the world was in the post-pandemic period and the influenza A(H1N1)pdm09(pdmH1N1)virus co-circulated with H3N2 and B virus seasonally(WHO,2010).The continuous surveillance on the pdmH1N1 virus in the post-pandemic period was recommended by WHO.In order to detect unusual events that might indicate a shift in severity disease,or emergence of a new virus,we collected a total of 312 throat swabs of laboratory-confirmed pdmHlNl patients from Hunan and Jilin provinces in

HIV prevalence in suspected Ebola cases during the 2014-2016 Ebola epidemic in Sierra Leone

Background:The 2014-2016 Ebola virus epidemic in West Africa was the largest outbreak of Ebola virus disease(EVD)in history.Clarifying the influence of other prevalent diseases such as human immunodeficiency virus infection and acquired immune deficiency syndrome(HIV/AIDS)will help improve treatment and supportive care of patients with EVD.Case presentation:We examined HIV and hepatitis C virus(HCV)antibody prevalence among suspected EVD cases from the Sierra Leone-China Friendship Biological Safety Laboratory during the epidemic in Sierra Leone.HIV and HCV antibodies were tested in 678 EVD-negative samples by enzyme-linked immunosorbent assay.A high HIV prevalence(17.6%)and low HCV prevalence(0.22%)were observed among the suspected cases.Notably,we found decreased HIV positive rates among the suspected cases over the course of the epidemic.This suggests a potentially beneficial effect of an improved public health system after assistance from the World Health Organization and other international aid organizations.Conclusions:This EVD epidemic had a considerable impact on the public health system and influenced the prevalence of HIV found among suspected cases in Sierra Leone,but also provided an opportunity to establish a better surveillance network for infectious diseases.

A practical community-based response strategy to interrupt Ebola transmission in sierra Leone, 2014–2015

Background:The Ebola virus disease spread rapidly in West Africa in 2014,leading to the loss of thousands of lives.Community engagement was one of the key strategies to interrupt Ebola transmission,and practical community level measures needed to be explored in the field and tailored to the specific context of communities.Methods:First,community-level education on Ebola virus disease(EVD)prevention was launched for the community’s social mobilizers in six districts in Sierra Leone beginning in November 2014.Then,from January to May of 2015,in three pilot communities,local trained community members were organized to engage in implementation of EVD prevention and transmission interruption measures,by involving them in alert case report,contact tracing,and social mobilization.The epidemiological indicators of transmission interruption in three study communities were evaluated.Results:A total of 6016 community social mobilizers from 185 wards were trained by holding 279 workshops in the six districts,and EVD message reached an estimated 631680 residents.In three pilot communities,72 EVD alert cases were reported,with 70.8%of them detected by trained local community members,and 14 EVD cases were finally identified.Contact tracing detected 64.3%of EVD cases.The median duration of community infectivity for the cases was 1 day.The secondary attack rate was 4.2%,and no third generation of infection was triggered.No health worker was infected,and no unsafe burial and noncompliance to EVD control measures were recorded.The community-based measures were modeled to reduce 77 EVD cases,and the EVD-free goal was achieved four months earlier in study communities than whole country of Sierra Leone.Conclusions: The community-based strategy of social mobilization and community engagement was effective in casedetection and reducing the extent of Ebola transmission in a country with weak health system. The successfullypractical experience to reduce the risk of Ebola transmission in the community with poor resources would potentiallybe helpful for the global community to fight against the EVD and the other diseases in the future.