Epidemic Characteristics and Spatio-Temporal Patterns of HFRS in Qingdao City,China,2010-2022

Objective This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome(HFRS)in Qingdao City,China.Methods Information was collected on HFRS cases in Qingdao City from 2010 to 2022.Descriptive epidemiologic,seasonal decomposition,spatial autocorrelation,and spatio-temporal cluster analyses were performed.Results A total of 2,220 patients with HFRS were reported over the study period,with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52%.The male:female ratio was 2.8:1.75.3%of patients were aged between 16 and 60 years old,75.3%of patients were farmers,and 11.6%had both“three red”and“three pain”symptoms.The HFRS epidemic showed two-peak seasonality:the primary fall-winter peak and the minor spring peak.The HFRS epidemic presented highly spatially heterogeneous,street/township-level hot spots that were mostly distributed in Huangdao,Pingdu,and Jiaozhou.The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak.Conclusion The distribution of HFRS in Qingdao exhibited periodic,seasonal,and regional characteristics,with high spatial clustering heterogeneity.The typical symptoms of“three red”and“three pain”in patients with HFRS were not obvious.

Risk of Developing Non-Alcoholic Fatty Liver Disease Over Time in a Cohort of the Elderly in Qingdao,China

Nonalcoholic fatty liver disease(NAFLD)is characterized by fat accumulation in the liver in the absence of alcohol consumption and comprises a variety of conditions such as simple steatosis,nonalcoholic steatohepatitis,fibrosis,and cirrhosis^([1]).More than one-quarter of the world’s population experience NAFLD^([2]).The prevalence of NAFLD in China increased from 23.8%in 2001 to 32.9%in 2018,indicating that hepatitis B virus is the primary cause of chronic liver disease^([3]).

The Ability of Baseline Triglycerides and Total Cholesterol Concentrations to Predict Incidence of Type 2 Diabetes Mellitus in Chinese Men and Women:A Longitudinal Study in Qingdao, China

Objectives The purpose of this study was to assess the association between triglycerides(TG),total cholesterol(TC)at baseline,and type 2 diabetes mellitus(T2DM)incidence in a general Chinese population.Further,it aimed to evaluate the ability of TG and TC to predict T2DM incidence.Methods Qingdao Diabetes Prevention Program participants recruited between 2006 and 2009 were followed up in 2012–2015.TG,TC,and T2DM status were measured.Cox proportional hazards models were used to estimate the association between TG,TC,and T2DM incidence.The receiver operating characteristic(ROC)curve was used to evaluate the ability of TG and TC to identify T2DM participants.Results The incidence of T2DM significantly increased with TG in women and TC in both men and women(Ptrend<0.05).Univariate Cox regression indicated that higher TG{borderline high TG[hazards ratio(HR):2.05;95%confidence interval(CI):1.40,3.00]and hypertriglyceridemia[HR:2.64;95%CI:1.68,4.15]}and TC[hypercholesterolemia(HR:2.05;95%CI:1.43,2.95)]were significantly associated with increased risk of T2DM incidence in women but not in men.Multivariate Cox regression showed that hypertriglyceridemia in women(HR:1.78,95%CI:1.07,2.97),borderline high TC in men(HR:1.61,95%CI:1.04,2.48),and hypercholesterolemia in women(HR:1.68,95%CI:1.81,2.61)had a higher significant risk of T2DM incidence.The optimal cutoff values of TG were>1.15 and>1.23 mmol/L in men and women,respectively.For TC,they were>5.17 and>5.77 mmol/L in men and women,respectively.The area under the ROCs of TG and TC were 0.54(0.51–0.57)and 0.55(0.52–0.58),respectively,in men,and 0.60(0.58–0.62)and 0.59(0.56–0.61),respectively,in women.Conclusion Elevated TG and TC were risk factors for T2DM incidence.However,no predictive capacity was found for both factors to identify T2DM incidence in Chinese men and women.Hence,TG and TC levels in both Chinese men and women might be used for decreasing the incidence of T2DM but no clinical predictive capacity for T2DM.

Genome-wide identification and spatiotemporal expression profiling of zinc finger SWIM domain-containing protein family genes

The biological function of the novel zinc-finger SWIM domain-containing protein family(ZSWIM)during embryonic development remains elusive.Here,we conducted a genome-wide analysis to explore the evolutionary processes of the ZSWIM gene family members in mice,Xenopus tropicalis,zebrafish,and humans.We identified nine putative ZSWIM genes in the human and mouse genome,eight in the Xenopus genome,and five in the zebrafish genome.Based on multiple sequence alignment,three members,ZSWIM5,ZSWIM6,and ZSWIM8,demonstrated the highest homology across all four species.Using available RNA sequencing(RNAseq)data,ZSWIM genes were found to be widely expressed across different tissues,with distinct tissuespecific properties.To identify the functions of the ZSWIM protein family during embryogenesis,we examined temporal and spatial expression patterns of zswim family genes in Xenopus embryos.Quantitative real-time polymerase chain reaction(qRT-PCR)revealed that each member had a distinct expression profile.Whole-mount in situ hybridization showed that both zswim1 and zswim3 were maternally expressed genes;zswim5 and zswim6were expressed throughout embryogenesis and displayed dynamic expression in the brain,eyes,somite,and bronchial arch at the late tailbud stages;zswim7 was detected in the eye area;zswim8 showed a dynamic expression pattern during the tailbud stages,with expression detected in the brain,eyes,and somite;zswim9 was faintly expressed throughout embryonic development.This study provides a foundation for future research to delineate the functions of ZSWIM gene members.

Changes in the Non-targeted Metabolomic Profile of Three-year-old Toddlers with Elevated Exposure to Polycyclic Aromatic Hydrocarbons

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota.Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq.Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336–0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34–0.55),which were mainly involved in neurodevelopment.Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

A Case of Psittacosis-Qingdao City,Shandong Province,China,May 2023

A case of psittacosis was identified in Qingdao City,Shandong Province on May 4,2023.The patient,a 69-year-old retired male,was admitted to a medical facility on April 22,2023.His symptoms,which had persisted for two days prior to his admission,included a fever(reaching 38.4°C at its peak),an escalating cough,and wheezing,none of which had been previously treated.

Rodent Ecology and Etiological Investigation in China:Results from Vector Biology Surveillance—Shandong Province,China,2012–2022

Introduction:Rodents are hosts of a wide range of zoonotic disease pathogens which threaten human health.However,comprehensive investigations of rodent ecology and etiology in Shandong are lacking.Thus,we aimed to analyze rodent ecology and infection with relevant pathogens in Shandong Province,China.Methods:Rodent survey data collected from 2012 to 2022 in Shandong Province were used in this study.Rodents captured from 2020 to 2022 were identified to species and tested for pathogens.Results:From 2012 to 2022,4,145 rodents were captured,with an average capture rate of 0.70%.High capture rates were observed in rural residential areas and other habitats,such as farmland and forestland.Rattus norvegicus(R.norvegicus)was the dominant species,followed by Mus musculus(M.musculus).The regions with the highest capture rates of R.norvegicus were Dongying(0.82%)and Heze(0.63%),while M.musculus was more prevalent in Dongying(0.81%)and Weihai(0.56%).Rodent capture rates were highest between March and September.The positive detection rates of Hantavirus(HV),Leptospira interrogans(L.interrogans),Rickettsia typhi(R.typhi),Anaplasma phagocytophilum(A.phagocytophilum),and Francisella tularensis(F.tularensis)in rodents were 2.58%,1.10%,0.94%,0.16%,and 0.19%,respectively.Conclusions:The rodent capture rate in human habitation environments has trended downward in Shandong Province,with R.norvegicus and M.musculus being the dominant species.Rodent infection risk from HV,L.interrogans,and R.typhi showed seasonal variation.Strengthening rodent surveillance and maintaining a low capture rate of host animals could be pivotal for preventing and controlling relevant rodent-borne diseases in high-risk areas.

Long Distance Transmission of SARS-CoV-2 from Contaminated Cold Chain Products to Humans——Qingdao City,Shandong Province,China,September 2020

Summary What is already known about this topic?Though coronavirus disease 2019(COVID-19)has largely been controlled in China,several outbreaks of COVID-19 have occurred from importation of cases or of suspected virus-contaminated products.Though several outbreaks have been traced to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)isolated on the outer packaging of cold chain products,live virus has not been obtained.

A Nosocomial COVID-19 Outbreak Initiated by an Infected Dockworker at Qingdao City Port-Shandong Province, China, October, 2020

On October 10,2020,3 cases of coronavirus disease 2019(COVID-19)were detected via routine preadmission nucleic acid screening of inpatients and their visitors at Qingdao Central Hospital.The 3 cases were all related to the Qingdao Chest Hospital.An additional 9 cases were discovered and confirmed through tracing and testing contacts of the 3 initial cases.Viral isolates from all 12 cases were found to have high degrees of genetic homology with the viral isolate from a dockworker at Qingdao Port,referred to as Patient A in this report.A joint investigation team was formed to determine the source of infection and the scale of the outbreak,and to prevent further spread of the virus.

Effect of Human Cytomegalovirus Infection on Nerve Growth Factor Expression in Human Glioma U251 Cells

Objective To explore the change of endogenic nerve growth factor （NGF） expression in human glioma cells infected with human cytomegalovirus （HCMV）. Methods U251 cells were cultured in RPMI 1640 culture medium and infected with HCMV AD 169 strain in vitro to establish a cell model of viral infection. Morphologic changes of U251 cells were observed under inverted microscope before and after infection with HCMV. Expression of NGF gene and protein of cells was detected by RT-PCR and Western blotting before and after infection with HCMV. Results The cytopathic effects of HCMV-infected cells appeared on day 5 after infection. However, differential NGF expression was evident on day 7. NGF expression was decreased significantly in U251 cells on day 7 after infection in comparison with control group （P〈0.05）. Conclusion HCMV can down-regulate endogenous NGF levels in human glioma cell line U251.

Twin-Based DNA Methylation Analysis Takes the Center Stage of Studies of Human Complex Diseases

The etiology of complex diseases is characterized by the interaction between the genome and environmental conditions and the interface of epigenetics may be a central mechanism. Current technologies already allow us high-throughput profiling of epigenetic patterns at genome level. However, our understanding of the epigenetic processes remains limited. Twins are special samples in genetic studies due to their genetic similarity and rearing-environment sharing. In the past decades, twins have made a great contribution in dissecting the genetic and environmental contributions to human diseases and complex traits. In the era of functional genomics, the valuable samples of twins are helping to bridge the gap between gene activity and environmental conditions through epigenetic mech- anisms unlimited to DNA sequence variations. We review the recent progresses in using twins to study disease-related molecular epigenetic pbenotypes and link them with environmental exposures especially early life events. Various study designs and application issues will be highlighted and discussed with aim at making uses of twins in assessing the environmental impact on epigenetic changes during the development of complex diseases.

HCMV Infection Depress NGF Expression in Human Glioma Cells

Human cytomegalovirus （HCMV） is the most common cause of congenital infection, resulting in birth defects such as microcephaly. In this study, RT-PCR and Western Blotting were performed to quantify the regulation of endogenic nerve growth factor expression in neuroglia ceils by HCMV infection. The results showed that basal, endogenous NGF expression in U251 was unchanged during early HCMV infection. NGF expression is strongly down-regulated during the latent phase of infection. These results suggest that HCMV can depress the NGF expression in U251 cells.

A Hospital Superspreading Event of COVID-19--Qingdao City,Shandong Province,China,2020

Superspreaders were defined as the minority of individuals who infect disproportionately more susceptible contacts,especially when compared to the majority of individuals who infect few or no others.Superspreading events,i.e.events involving superspreaders,highlight the limitations of basic reproduction number(R0),which represented the average dynamics of transmission.

Emergence of Zika Virus in Culex tritaeniorhynchus and Anopheles sinensis Mosquitoes in China

Zika virus(ZIKV)has been isolated from mosquitoes such as Aedes,Mansonia uniformis,and Culex perfuscus;However,the isolation of ZIKV from Anopheles sinensis and Culex tritaeniorhynchus has not yet been reported.In June and July2018,22,985 mosquitoes and 57,500 midges were collected in Jiangxi Province in southeastern China.Among them,six strains of ZIKV were isolated from mosquitoes:four from An.sinensis and two from Cx.tritaeniorhynchus.Molecular genetic analysis showed that the ZIKV isolated from An.sinensis and Cx.tritaeniorhynchus belonged to genotype 2 in the Asian evolutionary branch of ZIKV.In addition,the ZIKV strains isolated from An.sinensis and Cx.tritaeniorhynchus had amino acid substitutions identical to ZIKV strains prevalent in South America since 2015.This study is the first to isolate ZIKV from mosquito specimens collected in the wild of Jiangxi Province,China;This is also the first time that ZIKV has been isolated from An.sinensis and Cx.tritaeniorhynchus.Given that An.sinensis and Cx.tritaeniorhynchus have a very wide geographical distribution in China and even in eastern and southern Asia,the isolation of several strains of ZIKV from these two mosquitoes poses new challenges for the prevention and control of ZIKV infection in the mainland of China and countries and regions with the same distribution of mosquitoes.

Profiles of SARS-CoV-2 RNA and Antibodies in Inpatients with COVID-19 not Related with Clinical Manifestation: A Single Centre Study

Dear Editor,A novel coronavirus disease(COVID-19)caused by acute respiratory syndrome coronavirus 2(SARS-Co V-2)first broke out in Wuhan,Hubei Province,China,in 2019.More than 50 million cases of COVID-19 have been confirmed globally with 1,280,868 deaths reported as of November12,2020(https://covid19.who.int/).

A Limited Spreading Event of COVID-19 Caused by Delta Variant in a Cosmetic Hospital—Yantai City,Shandong Province,China,2021

Summary What is already known about this topic?Coronavirus disease 2019(COVID-19)outbreaks in the past were mostly caused by overseas transmission,but if control measures are not appropriately applied,domestic transmission could also cause large-scale local epidemics.What is added by this report?This report covers all information of epidemic investigation processes,epidemiological characteristics and exposure history,transmission chains,sequencing results as well as public health measures taken for the COVID-19 cluster epidemic caused by the Delta variant in a cosmetic hospital in Yantai City in August 2021.What are the implications for public health practice?The information provided in this report,including active case finding,community management,and mass testing,may assist public health professionals in dealing with local COVID-19 epidemics caused by domestic transmission.

Co-Exposure to Multiple Pollutants and Its Cardiovascular Effects in a Subway System-Beijing Municipality,China,2017

Summary What is already known on this topic?With rapid urbanization,traffic-related air pollution has become a global concern.However,its association with cardiovascular health has not been fully elucidated.What is added by this report?This study provided novel evidence of the joint cardiovascular effect of multiple pollutants in subway cabins,further identified two pollutants that played dominant roles,and validated the effectiveness of targeted interventions.

Reactivation of Epstein-Barr virus in SFTSV infected patients

Background:Severe fever with thrombocytopenia syndrome(SFTS)is an emerging hemorrhagic fever caused by a tick-borne bunyavirus SFTSV with case fatality up to 30%.The reactivation of Epstein-Barr virus(EBV)has been proven to occur in individuals with various immune suppression conditions.Methods:Here,we diagnosed 22 SFTSV infected patients with PCR in a hospital in Shandong Province,China in 2020.To understand the consequences of SFTSV infection leading to EBV reactivation,we examined EBV reactivation in SFTSV-infected patients with PCR and RT-PCR.Results:We found that EBV was reactivated in 18.2%(4/22)of SFTS patients,suggesting that EBV reactivation is common in SFTS patients.Compared with SFTS patients without EBV reactivation,SFTS patients with EBV-reactivation had a significantly lower median level of serum albumin(32.45 g/L vs.26.95 g/L,p=0.03)and a significantly higher median number of urine red blood cells(0 cells/μL vs.9 cells/μL,p=0.04).Conclusion:SFTS infection can reactivate EBV in patients,which may make the clinical condition of patients worsen.

CD59 Silencing via Retrovirus-Mediated RNA Interference Enhanced Complement-Mediated Cell Damage in Ovary Cancer

CD59, belonging to membrane complement regulatory proteins （mCRPs）, inhibits the cytolytic activity of complement and is over-expressed in solid cancers, including ovary cancer. The aim of the present study was to construct recombinant retrovirus encoding shRNA targeted human CD59 and infect A2780 cells in order to investigate the relationship between decreased CD59 expression and tumorigenesis of ovary cancer, siCD59 and siCD59-C were successfully constructed and identified by PCR, restriction endonuclease analyses and DNA sequencing, respectively. The siCD59 was able to efficiently infect A2780 cells, which was confirmed by Western blotting. When incubated with fresh normal human serum （8%, v/v） for 1 h at 37℃, the cell viability was decreased and cell damage was increased in siCD59 infected A2780 cells compared to siCD59-C infected cells. This led to the activation of caspase-3. The apoptosis in siCD59 infected cells was shown with hypercondensed nuclei using Hoechst staining. Meanwhile, the weight of ovary tumor graft in nude mice was significantly decreased in siCD59 group compared to that of siCD59-C group. And the expression of CD59 protein in tumor tissue in siCD59 group was significantly decreased. These results suggested that CD59 silencing in ovary cancer cells v/a retrovirusmediated RNAi can enhance complement-mediated cell damage, inhibiting growth of ovary cancer. CD59 might be a potential target for gene therapy in ovary cancer. Cellular ＆ Molecular Immunology.

Cold-chain transportation in the frozen food industry may have caused a recurrence of COVID-19 cases in destination:Successful isolation of SARS-CoV-2 virus from the imported frozen cod package surface

Coronavirus disease 2019(COVID-19)pandemic has spread in 220 countries/regions towreak havoc to human beings around theworld.At present,the second wave of COVID-19 has begun in many European countries.The complete control of COVID-19 is very urgent.Although China quickly brought the virus under control,there have been eight sporadic outbreaks in China since then.Both in Xinfadi of Beijing and Dalian outbreak of COVID-19,environmental swab samples related to imported cold chain food were tested nucleic acid positive for SARS-CoV-2.In this outbreak in Qingdao,we directly isolated SARS-CoV-2 from the cod outer package's surface swab samples.This is the first time worldwide,SARS-CoV-2 were isolated from the imported frozen cod outer package's surface,which showed that imported frozen food industry could import SARS-CoV-2 virus.