DNA Methylation of KLRC1 and KLRC3 in Autoimmune Thyroiditis:Perspective of Different Water Iodine Exposure

Objective This study aimed to identify differentially methylated genes(DMGs) associated with natural killer cells in patients with autoimmune thyroiditis(AIT), focusing on the influence of varying water iodine exposure levels.Methods Participants were divided into categories based on median water iodine(MWI)concentrations: iodine-fortified areas(IFA, MWI < 10 μg/L), iodine-adequate areas(IAA, 40 ≤ MWI ≤ 100μg/L), and iodine-excessive areas(IEA, MWI > 300 μg/L). A total of 176 matched AIT cases and controls were recruited and divided into 89, 40, and 47 pairs for IFA, IAA, and IEA, respectively. DMGs were identified using 850K Bead Chip analysis for 10/10 paired samples. Validation of DNA methylation and m RNA expression levels of the DMGs was conducted using Methyl Target^(TM) and QRT-PCR for 176/176paired samples.Results KLRC1, KLRC3, and SH2D1B were identified as significant DMGs. Validation revealed that KLRC1 was hypomethylated and highly expressed, whereas KLRC3 was hypermethylated and highly expressed in individuals with AIT. Furthermore, KLRC1 was hypomethylated and highly expressed in both IFA and IEA.Conclusion The DNA methylation status of KLRC1 and KLRC3 may play crucial roles in AIT pathogenesis. Additionally, DNA methylation of KLRC1 seems to be influenced by different iodine concentrations in water.

Time Series and Spatial Epidemiological Analysis of the Prevalence of Iodine Deficiency Disorders in China

Objective To recognize the spatial and temporal characteristics of iodine deficiency disorders(IDD),China national IDD surveillance data for the years of 1995–2018 were analyzed.Methods Time series analysis was used to describe and predict the IDD related indicators,and spatial analysis was used to analyze the spatial distribution of salt iodine levels.Results In China,the median urinary iodine concentration increased in 1995–1997,then decreased to adequate levels,and are expected to remain appropriate in 2019–2022.The goiter rate continually decreased and is expected to be maintained at a low level.Since 2002,the coverage rates of iodized salt and the consumption rates of qualified iodized salt(the percentage of qualified iodized salt in all tested salt) increased and began to decline in 2012;they are expected to continue to decrease.Spatial epidemiological analysis indicated a positive spatial correlation in 2016–2018 and revealed feature regarding the spatial distribution of salt related indicators in coastal areas and areas near iodine-excess areas.Conclusions Iodine nutrition in China showed gradual improvements.However,a recent decline has been observed in some areas following changes in the iodized salt supply in China.In the future,more regulations regarding salt management should be issued to strengthen IDD control and prevention measures,and avoid the recurrence of IDD.

Murine model of acute myocarditis and cerebral cortical neuron edema induced by coxsackievirus B4

Globally, coxsackievirus B4 （CV-B4） has been continuously isolated and evidence suggests an association with the development of pancreatitis and type I diabetes. In addition, CV-B4 is also associated with myocarditis and severe central nervous system （CNS） complications, which remain poorly studied and understood. In the present study, we established an institute for Cancer Research （ICR） mouse model of CV-B4 infection and examined whether CV-B4 infection resulted in a predisposition to myocarditis and CNS infection. We found high survival in both the treatment and control group, with no significant differences in clinical outcomes observed. However, pathological lesions were evident in both brain and heart tissue of the CV-B4-infected mice. in addition, high viral loads were found in the neural and cardiac tissues as early as 2 days post infection. Expressions of IFN-y and IL-6 in sera were significantly higher in CV-B4-infected mice compared to uninfected negative controls, suggesting the involvement of these cytokines in the development of histopathological lesions. Our murine model successfully reproduced the acute myocarditis and cerebral cortical neuron edema induced by CV-B4, and may be useful for the evaluation of vaccine candidates and potential antivirals against CV-B4 infection.

Summary Analysis of National Surveillance on Kashin-Beck Disease from 1990 to 2023

Objective To analyze the epidemiological characteristics and epidemic situation of children with Kashin-Beck disease(KBD)in China,and provide the basis for formulating prevention and control measures.Methods Fixed-point monitoring,moving-point monitoring,and full coverage of monitoring were promoted successively from 1990 to 2023.Some children(7-12 years old)underwent clinical and right-hand X-ray examinations every year.According to the KBD diagnosis criteria,clinical and X-ray assessments were used to confirm the diagnosis.Results In 1990,the national KBD detectable rate was 21.01%.X-ray detection decreased to below 10%in 2003 and below 5%in 2007.Between 2010 and 2018,the prevalence of KBD in children was less than 0.4%,which fluctuated at a low level,and has decreased to 0%since 2019.Spatial epidemiological analysis indicated a spatial clustering of adult patients prevalence rate in the KBD areas.Conclusion The evaluation results of the elimination of KBD in China over the last 5 years showed that all villages in the monitored areas have reached the elimination standard.While the adult KBD patients still need for policy consideration and care.

Low Selenium and Low Protein Exacerbate Myocardial Damage in Keshan Disease by Affecting the PINK1/Parkin-mediated Mitochondrial Autophagy Pathway

Objective Keshan disease(KD)is a myocardial mitochondrial disease closely related to insufficient selenium(Se)and protein intake.PTEN induced putative kinase 1(PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the body.This study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial injury.Methods A low Se and low protein animal model was established.One hundred Wistar rats were randomly divided into 5 groups(control group,low Se group,low protein group,low Se+low protein group,and corn from KD area group).The JC-1 method was used to detect the mitochondrial membrane potential(MMP).ELISA was used to detect serum creatine kinase MB(CK-MB),cardiac troponin I(cTnI),and mitochondrial-glutamicoxalacetic transaminase(M-GOT)levels.RT-PCR and Western blot analysis were used to detect the expression of PINK1,Parkin,sequestome 1(P62),and microtubule-associated proteins1A/1B light chain 3B(MAP1LC3B).Results The MMP was significantly decreased and the activity of CK-MB,cTnI,and M-GOT significantly increased in each experimental group(low Se group,low protein group,low Se+low protein group and corn from KD area group)compared with the control group(P<0.05 for all).The mRNA and protein expression levels of PINK1,Parkin and MAP1LC3B were profoundly increased,and those of P62 markedly decreased in the experimental groups compared with the control group(P<0.05 for all).Conclusion Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.

A brief procedure for big data analysis of gene expression

There are a lot of biological and experimental data from genomics, proteomics, drug screening, medicinal chemistry, etc. A large amount of data must be analyzed by special methods of statistics, bioinformatics, and computer science. Big data analysis is an effective way to build scientific hypothesis and explore internal mechanism.Here, gene expression is taken as an example to illustrate the basic procedure of the big data analysis.

Novel astrovirus and paramyxovirus in Mongolian gerbils(Meriones unguiculatus)from China

DEAR EDITOR,Mongolian gerbils(Meriones unguiculatus)are small rodents belonging to the family Muridae and widely inhabit typical steppes and desert grasslands across northern China.Yet,few viruses in wild M.unguiculatus have been reported.Using meta-transcriptomic sequencing we identified two novel RNA viruses:an astrovirus,denoted Gerbil astrovirus(GeAstV).

Cold weather and Kashin-Beck disease

Kashin-Beck disease(KBD)is an endemic osteoarthropathy.Its distribution region covers a long and narrow belt on the Pacific side and belongs to continental climate with short summer,long frost period,and large temperature differences between day and night.In particular,KBD patients are typically scattered in the rural areas with seasonal features such as cold winters and rainy autumns.Etiological studies have demonstrated that the carrier of pathogenic factors is the grains produced in endemic areas.Risk factors for KBD include fungal contamination of grains due to poor storage conditions associated with cold weather.The epidemiological characteristics of KBD include agricultural area,early age of onset,gender equality,family aggregation,regional differences,and annual fluctuations.A series of preventive measures have been successfully taken in the past decades.National surveillance data indicate that the annual incidence of KBD is gradually declining.

Disease and Economic Burden of Kashin-Beck Disease—China,2021

What is already known about this topic?Kashin-Beck disease(KBD)is a chronic and degenerative osteoarthropathy characterized by cartilage degeneration.It is an endemic disease that is highly prevalent among the Chinese population and poses a significant health risk.What is added by this report?This is the first national report on the economic burden of KBD in China.According to the data from 2021,KBD has caused significant disease and economic burdens.The most substantial reduction in healthy life expectancy was observed among patients with degree II severity and those aged 60 years and older,resulting in a total indirect economic burden of 112.74 million Chinese Yuan(CNY).What are the implications for public health practice?The results of this study will contribute to informing the development of tailored prevention and control strategies by the government.These strategies will include targeted policies and recommendations for appropriate healthcare and financial subsidies,which will be based on the demographic characteristics of the endemic areas.

Pathogen genomic surveillance elucidates the origins, transmission and evolution of emerging viral agents in China

In the past twenty years, numerous novel zoonotic viral agents with pandemic potential have emerged in China, such as the severe acute respiratory syndrome(SARS) coronavirus and, more recently, the avian-origin influenza A/H7N9 virus, which have caused outbreaks among humans with high morbidity and mortality. In addition, several emerging and re-emerging viral pathogens have also been imported into China from travelers, e.g. the Middle East respiratory syndrome(MERS) coronavirus and Zika virus(ZIKV). Herein, we review these emerging viral pathogens in China and focus on how surveillance by pathogen genomics has been employed to discover and annotate novel pathogenic agents, identify natural reservoirs, monitor the transmission events and delineate their evolution and adaption to the human host. We also highlight the application of genomic sequencing in the recent Ebola epidemics in Western Africa. In summary, genomic sequencing has become a standard research tool in the field of emerging infectious diseases which has been proven invaluable in containing these viral infections and reducing burden of disease in humans and animals. Genomic surveillance of pathogenic agents will serve as a key epidemiological and research tool in the modern era of precision infectious diseases and in the future studies of virosphere.

The Asian Lineage of Zika Virus: Transmission and Evolution in Asia and the Americas

Since first isolation in 1947 from the Zika forest in Uganda, Zika virus(ZIKV) has been principally known as a benign agent associated with sporadic human infections in a restricted number of African countries. However, during 2015–2016,an Asian lineage of ZIKV caused an unprecedentedly large outbreak in the Americas and sizeable numbers of exported cases across the globe. In this review, we critically appraise the recent advances in molecular epidemiological studies of ZIKV performed to date, and we highlight the pivotal role played by genomic surveillance in elucidating the origins,dissemination and evolution of the Asian lineage of ZIKV in Asia and in the Americas.

Co-existence and co-infection of influenza A viruses and coronaviruses: Public health challenges

Since the 20th century,humans have lived through five pandemics caused by influenza A viruses(IAVs)(H1N1/1918,H2N2/1957,H3N2/1968,and H1N1/2009)and the coronavirus(CoV)severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).IAVs and CoVs both have broad host ranges and share multiple hosts.Virus co-circulation and even co-infections facilitate genetic reassortment among IAVs and recombination among CoVs,further altering virus evolution dynamics and generating novel variants with increased cross-species transmission risk.Moreover,SARS-CoV-2 may maintain longterm circulation in humans as seasonal IAVs.Co-existence and co-infection of both viruses in humans could alter disease transmission patterns and aggravate disease burden.Herein,we demonstrate how virus-host ecology correlates with the co-existence and co-infection of IAVs and/or CoVs,further affecting virus evolution and disease dynamics and burden,calling for active virus surveillance and countermeasures for future public health challenges.

Seroprevalence of influenza viruses in Shandong,Northern China during the COVID-19 pandemic

Nonpharmaceutical interventions(NPIs)have been commonly deployed to prevent and control the spread of the coronavirus disease 2019(COVID-19),resulting in a worldwide decline in influenza prevalence.However,the influenza risk in China warrants cautious assessment.We conducted a cross-sectional,seroepidemiological study in Shandong Province,Northern China in mid-2021.Hemagglutination inhibition was performed to test antibodies against four influenza vaccine strains.A combination of descriptive and meta-analyses was adopted to compare the seroprevalence of influenza antibodies before and during the COVID-19 pandemic.The overall seroprevalence values against A/H1N1pdm09,A/H3N2,B/Victoria,and B/Yamagata were 17.8%(95%CI 16.2%–19.5%),23.5%(95%CI 21.7%–25.4%),7.6%(95%CI 6.6%–8.7%),and 15.0(95%CI 13.5%–16.5%),respectively,in the study period.The overall vaccination rate was extremely low(2.6%).Our results revealed that antibody titers in vaccinated participants were significantly higher than those in unvaccinated individuals(P<0.001).Notably,the meta-analysis showed that antibodies against A/H1N1pdm09 and A/H3N2 were significantly low in adults after the COVID-19 pandemic(P<0.01).Increasing vaccination rates and maintaining NPIs are recommended to prevent an elevated influenza risk in China.

Ecology of avian influenza viruses in migratory birds wintering within the Yangtze River wetlands

Migratory birds are considered natural reservoirs of avian influenza A viruses(AIVs).To further our viral ecology knowledge and understand the subsequent risk posed by wild birds,we conducted a 4-year surveillance study of AIVs in the bird wintering wetlands of the Yangtze River,China.We collected over8000 samples and isolated 122 AIV strains.Analyses were then carried out with 108 novel sequenced genomes and data were deposited in GISAID and other public databases.The results showed that the Yangtze River wintering wetlands functioned as a mixing ground,where various subtypes of AIVs were detected harboring a high diversity of nucleotide sequences;moreover,a portion of AIV gene segments were persistent inter-seasonally.Phylogenetic incongruence presented complex reassortment events and distinct patterns among various subtypes.In addition,we observed that viral gene segments in wintering wetlands were closely related to known North American isolates,indicating that intercontinental gene flow occurred.Notably,highly pathogenic H5 and low pathogenic H9 viruses,which usually circulate in poultry,were found to have crossed the poultry/wild bird interface,with the viruses introduced to wintering birds.Overall,this study represented the largest AIV surveillance effort of wild birds within the Yangtze River wintering wetlands.Surveillance data highlighted the important role of wintering wild birds in the ecology of AIVs and may enable future early warnings of novel AIV emergence.

Genomic characterizations of H4 subtype avian influenza viruses from live poultry markets in Sichuan province of China, 2014–2015

Dear Editor,Avian influenza viruses （AIVs） have posed a serious threat to poultry production and public health. To date, more than fourteen AIV subtypes that are able to infect human beings have been documented. Also, it is suggested that new subtypes may be reported in the future, owing to the migration of wild birds and live poultry transportation （Gao, 2018）.Poultry may act as a potential incubator for novel subtypes of avian influenza virus （Bi et al., 2016a; Bi et al., 2016b; Liu et al., 2014a; Su et al., 2017）. Up to date.

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.

A Reemergent Case of COVID-19—Harbin City,Heilongjiang Province,China,April 9,2020

As of February 22,a total of 198 confirmed COVID-19 cases were reported in Harbin,Heilongjiang Province,and no new local cases were reported in Harbin over the next 54 days(1).However,on April 9,a newly confirmed COVID-19 case was reported with an unknown source of infection(2).The patient,a 54-year-old male,developed a fever on March 28 with the highest recorded temperature at 37.5℃.On April 7,the symptoms worsened and included dyspnea,cough,sputum,chest pain,and other symptoms,though he did not experience chest distress,heart palpitations,nausea and vomiting,abdominal pain or diarrhea.He went to the fever clinic of the Harbin Second Hospital and was admitted to the isolation ward with a temperature of 37.2°C.The patient also had a history of diabetes.

Genomic characterization of SARS-CoV-2 identified in a reemerging COVID-19 outbreak in Beijing's Xinfadi market in 2020

After 56 days without coronavirus disease 2019(COVID-19)cases,reemergent cases were reported in Beijing,China on June 11,2020.Here,we report the genetic characteristics of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)sequenced from the clinical specimens of 4 human cases and 2 environmental samples.The nucleotide similarity among six SARS-CoV-2 genomes ranged from 99.98%to 99.99%.Compared with the reference strain of SARS-CoV-2(GenBank No.NC_045512),all six genome sequences shared the same substitutions at nt241(C→T),nt3037(C→T),nt14408(C→T),nt23403(A→G),nt28881(G→A),nt28882(G→A),and nt28883(G→C),which are the characteristic nucleotide substitutions of L-lineage European branch I.This was also proved by themaximum likelihood phylogenetic tree based on the full-length genome of SARS-CoV-2.They also have a unique shared nucleotide substitution,nt6026(C→T),which is the characteristic nucleotide substitution of SARS-CoV-2 in Beijing's Xinfadi outbreak.It is noteworthy that there is an amino acid D614Gmutation caused by nt23403 substitution in all six genomes,which may enhance the virus's infectivity in humans and help it become the leading strain of the virus to spread around the world today.It is necessary to continuously monitor the genetic variation of SARS-CoV-2,focusing on the influence of key mutation sites of SARS-CoV-2 on viral transmission,clinical manifestations,severity,and course of disease.

Identification of a novel hepacivirus in Mongolian gerbil(Meriones unguiculatus)from Shaanxi,China

Dear Editor,Hepaciviruses,members of the family Flaviviridae,are enveloped viruses containing a single-stranded positive-sense RNA genome of approximately 8.9-10.5 kb in size(Simmonds et al.,2017).To date,15species(Hepacivirus A-N,and P)have been documented within the Hepacivirus genus that show distinct host ranges,including primates,bats,horses,donkeys,cows,and various rodents(Hartlage et al.,2016).

CASCIRE surveillance network and work on avian influenza viruses

Studies on influenza virus by Chinese Academy of Sciences(CAS)could be traced back as early as 2005 by the CAS Key Laboratory of Pathogenic Microbiology and Immunology(CASPMI),who discovered that Qinghai-like Clade 2.2H5N1 subtype highly pathogenic avian influenza virus(HPAIV)first caused severe outbreak in wild birds in Qinghai Lake(Liu et al.,2005).