Association of vaccine policy with virus infection and awareness of hepatitis B in Fujian, China.

China has regulated its hepatitis B vaccination policy. However, data on the prevalence of hepatitis B virus (HBV) infection have not been updated since 2014. In addition, the impact of the policy on awareness of hepatitis B is limited, especially in Fujian Province where HBV infection is highly prevalent. We conducted a sero-epidemiological survey in five national monitoring counties to address these concerns. A total of 5,873 subjects were included and classified into four birth cohorts according to the policy time nodes (1981, 1992, and 2002). The HBsAg carrier rate for the general population was 8.6% (95% confidence interval [CI]: 7.9-9.3). Compared with those born before 1981, adjusted odds ratios (OR) for HBV infection were 0.51 (95% CI: 0.43-0.62), 0.10 (0.08-0.12), and 0.015 (0.01-0.023) among the 1981-1991, 1992-2001, and ≥2002 birth cohorts, respectively; while the OR was 1.26 (1.00-1.57), 0.39 (0.26-0.58), and 0.019 (0.006-0.06) for HBsAg carriage, respectively. Among the 4865 residents aged ≥15 years, hepatitis B awareness has been declining since the introduction of the hepatitis B vaccine into the immunization program (ß = -0.25, SE = 0.08, P = .001, and ß = -0.20, SE = 0.08, P = .017 for 1992-2001 and ≥2002 birth cohort, respectively). This decline was obvious for the initiation time of the first dose of the hepatitis B vaccine. Although the hepatitis B vaccination policies have helped reduce the infection, the awareness has declined. More measures on the target population are warranted to improve the public's awareness of hepatitis B vaccination in the context of great achievements.

Mumps serological surveillance following 10 years of a one-dose mumps-containing-vaccine policy in Fujian Province, China.

BACKGROUND: Since 2008, Fujian province provided measles-rubella (MR) vaccine at 8 months followed by measles-mumps-rubella (MMR) vaccine at 18 months a one-dose mumps-containing-vaccine (MuCV) schedule. Several mumps outbreaks have occurred recently in Fujian. Serological surveillance can assess population immunity to mumps and identify risk factors for mumps. METHODS: We conducted a cross-sectional serosurvey of mumps IgG antibodies in the general population of Fujian Province in 2018 and compare results with a similar study conducted in 2009, when the routine schedule had no MuCV. We analyzed changes in mumps epidemiology after implementation of a one-dose MuCV vaccination strategy. RESULTS: Mumps seroprevalence was 78.6% (95% CI: 77.4-79.8), and the geometric mean concentration (GMC) of mumps antibodies was 245.8 IU/ml (95% CI:237.3-255.1). MuCV vaccination at 18 months resulted in increased seroprevalence and GMCs. Seroprevalence and GMCs varied by age, gender, and number of doses received. Except for children under 18 months, seroprevalence and GMCs were lowest among 10-15-year-olds. Each year after introduction of the one-dose MuCV vaccination policy, the highest incidence of mumps was among 4-6-year-olds and 9-15-year-olds, gradually shifting to older age groups. CONCLUSION: A one-dose mumps-containing vaccine schedule does not provide sustained and stable mumps immunity in Fujian. To reduce the risk of mumps, we recommend supplementary vaccination of children without a history of receiving at least one MuCV dose or who are seronegative at 10-15 years of age.

Melatonin Attenuates Cardiac Ischemia-Reperfusion Injury through Modulation of IP3R-Mediated Mitochondria-ER Contact.

Although the interplay between mitochondria and ER has been identified as a crucial regulator of cellular homeostasis, the pathogenic impact of alterations in mitochondria-ER contact sites (MERCS) during myocardial postischemic reperfusion (I/R) injury remains incompletely understood. Therefore, in our study, we explored the beneficial role played by melatonin in protecting cardiomyocytes against reperfusion injury via stabilizing mitochondria-ER interaction. In vitro exposure of H9C2 rat cardiomyocytes to hypoxia/reoxygenation (H/R) augmented mitochondrial ROS synthesis, suppressed both mitochondrial potential and ATP generation, and increased the mitochondrial permeability transition pore (mPTP) opening rate. Furthermore, H/R exposure upregulated the protein content of CHOP and caspase-12, two markers of ER stress, and enhanced the transcription of main MERCS tethering proteins, namely, Fis1, BAP31, Mfn2, and IP3R. Interestingly, all the above changes could be attenuated or reversed by melatonin treatment. Suggesting that melatonin-induced cardioprotection works through normalization of mitochondria-ER interaction, overexpression of IP3R abolished the protective actions offered by melatonin on mitochondria-ER fitness. These results expand our knowledge on the cardioprotective actions of melatonin during myocardial postischemic reperfusion damage and suggest that novel, more effective treatments for acute myocardial reperfusion injury might be achieved through modulation of mitochondria-ER interaction in cardiac cells.

Transmission Dynamics of the Rubella Virus Circulating in China During 2010-2019: 2 Lineage Switches Between Genotypes 1E and 2B.

BACKGROUND: To provide a better understanding of the progress on rubella control and elimination in China, a genetic analysis was conducted to examine the transmission pattern of the endemic rubella virus in China during 2010-2019. METHODS: A total of 4895 strains were obtained from 29 of the 31 provinces in mainland China during 2010-2019. The genotyping regions of the strains were amplified, determined, and assembled. Genotyping analysis and lineage division were performed by comparisons with the World Health Organization reference strains and reported lineage reference strains, respectively. Further phylogenetic analyses were performed to compare the genetic relationship. RESULTS: During 2010-2019, the domestic lineage 1E-L1 and multiple imported lineages of rubella viruses including 2B-L1, 1E-L2, and 2B-L2c were identified. Further analysis of the circulation trend of the different lineages indicated that 2 switches occurred among the lineages. The first shift was from lineage 1E-L1 to 2B-L1, which occurred around 2015-2016, followed by the lowest rubella incidence in 2017. The second shift was from lineage 2B-L1 to 1E-L2 and 2B-L2c, which occurred around 2018-2019, coinciding with rubella resurgence and the subsequent nationwide epidemic during 2018-2019. Insufficient genomic information worldwide made it impossible to trace the origin of the imported viruses. CONCLUSIONS: China was moving toward rubella elimination, as evidenced by the fact that previous endemic lineages were not detected. However, rubella reemerged in 2018 2019 due to the newly imported rubella viruses. Therefore, to realize the rubella elimination goal, joint efforts are required for all countries worldwide.

MicroRNA-140-5p aggravates hypertension and oxidative stress of atherosclerosis via targeting Nrf2 and Sirt2.

In the present study, the function of microRNA (miR)­140­5p on oxidative stress in mice with atherosclerosis was investigated. A reverse transcription­quantitative polymerase chain reaction assay was used to determine the expression of miR­140­5p. Oxidative stress kits and reactive oxygen species (ROS) kits were used to analyze alterations in oxidative stress and ROS levels. The alterations in protein expression were determined using western blot analysis and an immunofluorescence assay. miR­140­5p expression was increased in mice with atherosclerosis with hypertension. Consistently, miR­140­5p expression was also increased in mice with atherosclerosis. Upregulation of miR­140­5p increased oxidative stress and ROS levels by suppressing the protein expression of nuclear factor erythroid 2­related factor 2 (Nrf2), sirtuin 2 (Sirt2), Kelch­like enoyl­CoA hydratase­associated protein 1 (Keap1) and heme oxygenase 1 (HO­1) in vitro. By contrast, downregulation of miR­140­5p decreased oxidative stress and ROS levels by activating the protein expression of Nrf2, Sirt2, Keap1 and HO­1 in vitro. Sirt2 agonist or Nrf2 agonist inhibited the effects of miR­140­5p on oxidative stress in vitro. Collectively, these results suggested that miR­140­5p aggravated hypertension and oxidative stress of mice with atherosclerosis by targeting Nrf2 and Sirt2.

Comparison of Limus-Eluting and Paclitaxel-Eluting Stents for Coronary Intervention in Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) patients have worse adverse cardiovascular outcomes after percutaneous coronary intervention (PCI). Clinical outcomes comparing a limus-eluting stent (LES) to a paclitaxel-eluting stent (PES) in patients with CKD remain controversial.A systematic search was conducted using PubMed, EMBASE, and Cochrane Library. A pooled odds ratio (OR) and 95% confidence interval (CI) were used to calculate original data. We conducted heterogeneity, quality assessment, and publication bias analyses.A total of 17 trials involving 10,724 patients were included. No significant differences were found regarding target vessel revascularization, target lesion revascularization (TLR), stent thrombosis (ST), myocardial infarction (MI), all-cause mortality, and major adverse cardiac events (MACE) between first-generation LES implantation and PES implantation. Second-generation LES implantation was associated with lower rates of all-cause mortality (OR, 0.56; 95% CI, 0.39-0.82; P = 0.003), MACE (OR, 0.61; 95% CI, 0.38-0.97; P = 0.04), and ST (OR, 0.45; 95% CI, 0.26-0.77; P = 0.004) compared with PES implantation. In all, the long-term all-cause mortality rate was significantly lower after LES implantation than after PES implantation in patients with CKD (OR, 0.78; 95% CI, 0.66-0.93; P = 0.004). However, second-generation LES implantation resulted in a higher rate of TLR (OR, 2.23; 95% CI, 1.53-3.25; P < 0.001) than PES implantation in dialysis patients.In patients with CKD, first-generation LES and PES implantation had comparable mortality and morbidity. Second-generation LES implantation was superior to PES in reducing long-term mortality, MACE, and ST. However, PES may be more effective than LES in dialysis patients.

Immunomagnetic enrichment to evaluate the role of home environment specimens in transmission of enterovirus 71.

Enterovirus 71 (EV71) immunomagnetic enrichment technique and routine detection methods were combined to detect swab environmental specimens to elucidate the role of environmental specimens in the spread of EV71. Immunomagnetic beads with specific enrichment of EV71 virus were prepared, then the beads were used to absorb the EV71 virus from environmental samples. Obtained immunomagnetic bead-virus complexes were detected by RT-PCR, RT-qPCR and cell culture. Isolated virus were subjected to VP1 full-length amplification and homology analysis was performed. A total of 4 µg of EV71 monoclonal antibody was mixed with 50 µl magnetic beads, and the highest coating efficiency was reached after incubating at room temperature for 2 h. Satisfactory enrichment effect was achieved by adding 50 µl immunomagnetic beads to 1.5 ml sample and shaking at room temperature for 2 h. The method of EV71 enrichment has high sensitivity and specificity. A total of 346 specimens after enrichment by immunomagnetic beads, the positive rates of RT-qPCR, RT-PCR and cell culture were 20.52, 5.78, and 9.25%, respectively, which were also significantly higher than those before enrichment (15.90, 3.47 and 4.05%; P<0.05). After enrichment with immunomagnetic beads, isolation rate of EV71 virus from case specimens and home environment specimens increased from 27.45 to 43.14% and from 0 to 5.29%, respectively. In home environment-positive specimens, positive rate of toys and stationery was high (52.00 and 24.00%, respectively). In kindergarten environmental samples, the positive rate of RT-qPCR was 6.12%, and EV71 virus was not isolated. Sequence analysis showed that the nucleotide homology of case isolates and home environment isolates was 98.0-100%.

[Molecular Epidemiology of Echovirus 30 in Longyan City, Fujian, China, 2011～2014].

We studied the molecular epidemiology of echovirus 30 in sporadic cases of viral encephalitis in Longyan City, Fujian, China, from 2011 to 2014.Specimens of cerebrospinal fluid from patients diagnosed with viral encephalitis or infection of the central nervous system were collected. Viruses were isolated by cell culture. Identification of the echovirus 30 serotype and genetic analyses were undertaken. Amplification of virus protein(VP)-1gene sequences was done by reverse transcription-polymerase chain reaction. A total of 168 strains of enterovirus were isolated in 608 cases from 2011 to 2014,of which 60 strains were echovirus 30.The epidemic "peak" of echovirus 30 was from June to August. The age range of patients was wide, with 65% of cases under 10 years of age. Clinical manifestations were pyrexia, headache and vomiting.Cerebrospinal fluid was clear, and the number of cells and protein was increased. The epidemic strains in Longyan City from 2011 to 2014belonged to the "h" genotype, and there were two transmission chains. Compared with the viral encephalitis strains from the outbreak in Fujian Province in 2011,they were highly homologous, but a new amino-acid variation of VP1 protein I 120 V was found in Longyan City strains from 2014.The viral encephalitis strains from the outbreak in Fujian Province in 2011 were present in Longyan City strains, and two transmission chains are still circulating,but there were new mutations in the virus strains from 2014.Continuous monitoring will aid:(i)early detection of viral variants that may accumulate;(ii)assessment of the risk of epidemics.

[Molecular epidemiology of HFMD-associated pathogen coxsackievirus A6 in Fujian Province, 2011-2013].

In order to characterize the molecular epidemiology of HFMD-associated Coxsackievirus A6 (CVA6) in Fujian Province, a total of 1340 specimens from non-EV71 non-CVA16 HFMD patients were collected during 2011-2013. Isolated virus strains were identified and subtyped. Full-length coding regions for the VP1 gene of the predominant serotype CVA6 isolates were amplified and sequenced. Among the 375 non-EV71 non-CVA16 HFMD cases confirmed by virus isolation and molecular subtyping, 182 (48.5%) were found to be caused by CVA6, accounting for 7.9%, 16.2% and 39.6% HFMD-associated enteroviruses in FujianProvince during 2011, 2012, and 2013, respectively. Compared with general features observed in the HFMD epidemic, no difference in CVA6-specificity or severity rates was observed between geographical origins, gender, or age groups. Nucleotide sequence analyses of VP1 genes revealed high diversity levels of 16.2%-18.6% among CVA6 strains from Fujian Province, in contrast to the prototype CVA6 strain, and showed low levels of diversity in the amino acid sequences (4.3%-6.2%). Phylogenetic analysis also indicated that CVA6 isolates from Fujian Province were distinct from the prototype strain and other isolates from abroad; however, it was homologous to domestic strains, although the Fujian isolates clustered into multiple branches. These results suggested that significant changes in the pathogenic spectrum of HFMD in Fujian Province occurred during 2011-2013, as CVA6 was one of the predominant serotypes of HFMD. CVA6 isolates from Fujian Province were co-circulating and co-evolving with other domestic strains as multiple closely related CVA6 transmission chains were observed in Fujian Province overall and within each prefecture.

Genetic characterization of the hemagglutinin genes of wild-type measles virus circulating in china, 1993-2009.

BACKGROUND: China experienced several large measles outbreaks in the past two decades, and a series of enhanced control measures were implemented to achieve the goal of measles elimination. Molecular epidemiologic surveillance of wild-type measles viruses (MeV) provides valuable information about the viral transmission patterns. Since 1993, virologic surveillnace has confirmed that a single endemic genotype H1 viruses have been predominantly circulating in China. A component of molecular surveillance is to monitor the genetic characteristics of the hemagglutinin (H) gene of MeV, the major target for virus neutralizing antibodies. PRINCIPAL FINDINGS: Analysis of the sequences of the complete H gene from 56 representative wild-type MeV strains circulating in China during 1993-2009 showed that the H gene sequences were clustered into 2 groups, cluster 1 and cluster 2. Cluster1 strains were the most frequently detected cluster and had a widespread distribution in China after 2000. The predicted amino acid sequences of the H protein were relatively conserved at most of the functionally significant amino acid positions. However, most of the genotype H1 cluster1 viruses had an amino acid substitution (Ser240Asn), which removed a predicted N-linked glycosylation site. In addition, the substitution of Pro397Leu in the hemagglutinin noose epitope (HNE) was identified in 23 of 56 strains. The evolutionary rate of the H gene of the genotype H1 viruses was estimated to be approximately 0.76×10(-3) substitutions per site per year, and the ratio of dN to dS (dN/dS) was <1 indicating the absence of selective pressure. CONCLUSIONS: Although H genes of the genotype H1 strains were conserved and not subjected to selective pressure, several amino acid substitutions were observed in functionally important positions. Therefore the antigenic and genetic properties of H genes of wild-type MeVs should be monitored as part of routine molecular surveillance for measles in China.

Molecular epidemiology of Echovirus 30 in Fujian, China between 2001 and 2011.

Echovirus 30 (E-30) was responsible for an outbreak of aseptic meningitis between April 1 and June 2, 2011 in Fujian Province, China. A molecular epidemiology study of 115 E-30 strains was performed to characterize the genetic features of the etiologic agent of the 2011 aseptic meningitis outbreak. The phylogenetic trees of the complete VP1 gene (876 bp) from 74 of 115 isolates and 50 reference sequences were analyzed. Three lineages (E-30_h, i, and j) were detected that had co-circulated in Fujian in the last decade, of which E-30_j was new. The other 72 Fujian strains and 16 representative strains from other provinces of China all belong to E-30_h and E-30_i. Two distinct E-30 clusters including virus isolates obtained during adult surveillance were associated with the 2011 outbreak and differed from Fujian isolates prior to 2011, suggesting that the viruses may vary and adult infections play an important role in viral transmission. Thus, the multiple lineages of E-30 in Fujian and variant viruses enhanced transmissibility, which may be related to the epidemic activity of E-30.

Molecular epidemiology of hepatitis C virus among different groups of people in the province of Fujian, China.

Genotyping of hepatitis C virus (HCV) can provide valuable information for prognosis and treatment duration prediction. To explore the genetic diversity of HCV in Fujian Province, China, 112, 104 and 48 anti-HCV-positive serum samples were collected from volunteer blood donors, IDUs and patients, respectively, from Jan 2008 to Dec 2008 and were genotyped through sequence analysis, followed by phylogenetic analysis in the C/E1 and NS5B regions. Genotypes could be determined for 85.61 and 84.85 % of samples in the C/E1 and NS5B region, respectively. 6a was the most prevalent subtype, which accounted for 42.04 and 43.75 % in the C/E1 and NS5B region, respectively. Mixed infection and potential recombination were detected in this study. Kappa tests indicated that similar results were obtained by two genotyping methods targeting the C/E1 and NS5B regions. The differences in the main prevalent subtype between the three target groups suggest diversity of HCV prevalence in different populations.

Emergence and continuous evolution of genotype 1E rubella viruses in China.

In China, rubella vaccination was introduced into the national immunization program in 2008, and a rubella epidemic occurred in the same year. In order to know whether changes in the genotypic distribution of rubella viruses have occurred in the postvaccination era, we investigate in detail the epidemiological profile of rubella in China and estimate the evolutionary rate, molecular clock phylogeny, and demographic history of the predominant rubella virus genotypes circulating in China using Bayesian Markov chain Monte Carlo phylodynamic analyses. 1E was found to be the predominant rubella virus genotype since its initial isolation in China in 2001, and no genotypic shift has occurred since then. The results suggest that the global 1E genotype may have diverged in 1995 and that it has evolved at a mutation rate of 1.65 × 10(-3) per site per year. The Chinese 1E rubella virus isolates were grouped into either cluster 1 or cluster 2, which likely originated in 1997 and 2006, respectively. Cluster 1 viruses were found in all provinces examined in this study and had a mutation rate of 1.90 × 10(-3) per site per year. The effective number of infections remained constant until 2007, and along with the introduction of rubella vaccine into the national immunization program, although the circulation of cluster 1 viruses has not been interrupted, some viral lineages have disappeared, and the epidemic started a decline that led to a decrease in the effective population size. Cluster 2 viruses were found only in Hainan Province, likely because of importation.

[Analysis of neutralized antibody level of the poliomyelitis in healthy population in Fujian province].

OBJECTIVE: To understand the neutralized antibody level of the poliomyelitis among healthy people and provide scientific evidence for the immunization strategy since routine and intensified immunization with oral polio vaccine (OPV) in Fujian province. METHODS: The poliomyelitis antibody level of healthy people were detected by neutralization test of the micro cells. RESULTS: The neutralizing antibody positive rates were 99.0%, 99.3%, 97.5% and GMTs were 1:79.1, 1:31.2, 1:24.7 for polio I, II, III respectively in 400 serum specimens from 1-59 years old. GMTs present a trend of decreasing as age's increasing. CONCLUSION: A protective barrier had been built against poliomyelitis in healthy people in Fujian province through routine and intensified immunization with OPV.

[Analysis of the chemical constituents of essential oil from Magnolia biondii by GC-MS].

OBJECTIVE: The chemical components of essential oil from Magnolia biondii were analyzed by GC-MS. METHODS: Essential oil was extracted by steam distillation (SD). The chemical components of essential oil were analyzed by GC-MS. RESULTS: The chemical components in the oil were qualitatively and quantitatively analyzed by GC-MS. 63 components were separated and 50 components were identified. The main components were Eucalyptol (28.92%), P-pinene (12.39%), alpha-Terpineol (8.28%). CONCLUSION: This is the first time to adopt GC-MS to analyze the chemical components of volatile oil of Magnolia biondii, and this study can provide science basis for further research development of Magnolia biondii.

Molecular epidemiology of measles viruses in China, 1995-2003.

This report describes the genetic characterization of 297 wild-type measles viruses that were isolated in 24 provinces of China between 1995 and 2003. Phylogenetic analysis of the N gene sequences showed that all of the isolates belonged to genotype H1 except 3 isolates, which were genotype A. The nucleotide sequence and predicted amino acid homologies of the 294-genotype H1 strains were 94.7%-100% and 93.3%-100%, respectively. The genotype H1 isolates were divided into 2 clusters, which differed by approximately 2.9% at the nucleotide level. Viruses from both clusters were distributed throughout China with no apparent geographic restriction and multiple co-circulating lineages were present in many provinces. Even though other measles genotypes have been detected in countries that border China, this report shows that genotype H1 is widely distributed throughout the country and that China has a single, endemic genotype. This important baseline data will help to monitor the progress of measles control in China.

[Molecular identification and genetic analysis of an echovirus 19-associated epidemic of aseptic encephalitis].

OBJECTIVE: To ascertain the pathogen of aseptic encephalitis epidemic in Long-Yan city in Fujian, and to find out the genetic characteristics of the virus. METHODS: Rapid detection of enteroviral RNA by reverse transcription polymerasechain reaction (RT-PCR) was directly carried out in cerebrospinal fluid(CSF) to isolate and identify the viruses from CSF at the same time, and to detect the neutralization antibody in two serum specimens collected in acute and convalescence phase. Nucleotides of VP1 region was also analyzed by constructing phylogenetic tree. RESULTS: ECHO 19 infection was rapidly diagnosed and sequence analysed by RT-PCR, and then echovirus type 19 from 16 of 30 CSF samples (53.33%) was isolated and detected using RD and Hep-2 cells simultaneity. The titer of ECHO 19 neutralization antibody became positive or increased by 4 times from acute to convalescence phase in 4 of the 5 patients. Phylogenetic analyses of the VP1 genes of these isolates showed that their nucleotides identity were 98.9% -100.0% which were different from those ECHO 19 from GeneBank database by 13.0%-22.4%. CONCLUSION: The etiology of the epidemic of aseptic encephalitis was attributed to ECHO 19. The method of molecular identification not only provided rapid diagnosis of enterovirus infections, but also information about the genetic character of the viruses.