Effect of non-pharmacological interventions on pain in preterm infants in the neonatal intensive care unit: a network meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness of different non-pharmacological interventions for pain management in preterm infants and provide high-quality clinical evidence. METHODS: Randomized controlled trials (RCTs) of various non-pharmacological interventions for pain management in preterm infants were searched from PubMed, Web of Science, Embase, and the Cochrane Library from 2000 to the present (updated March 2023). The primary outcome was pain score reported as standardized mean difference (SMD). The secondary outcomes were oxygen saturation and heart rate reported as the same form. RESULTS: Thirty five RCTs of 2134 preterm infants were included in the meta-analysis, involving 6 interventions: olfactory stimulation, combined oral sucrose and non-nutritive sucking (OS + NNS), facilitated tucking, auditory intervention, tactile relief, and mixed intervention. Based on moderate-quality evidence, OS + NNS (OR: 3.92, 95% CI: 1.72, 6.15, SUCRA score: 0.73), facilitated tucking (OR: 2.51, 95% CI: 1.15, 3.90, SUCRA score: 0.29), auditory intervention (OR: 2.48, 95% CI: 0.91, 4.10, SUCRA score: 0.27), olfactory stimulation (OR: 1.80, 95% CI: 0.51, 3.14, SUCRA score: 0.25), and mixed intervention (OR: 2.26, 95% CI: 0.10, 4.38, SUCRA score: 0.14) were all superior to the control group for pain relief. For oxygen saturation, facilitated tucking (OR: 1.94, 95% CI: 0.66, 3.35, SUCRA score: 0.64) and auditory intervention (OR: 1.04, 95% CI: 0.22, 2.04, SUCRA score: 0.36) were superior to the control. For heart rate, none of the comparisons between the various interventions were statistically significant. CONCLUSION: This study showed that there are notable variations in the effectiveness of different non-pharmacological interventions in terms of pain scores and oxygen saturation. However, there was no evidence of any improvement in heart rate.

Alternative Pathway to Phase Down Coal Power and Achieve Negative Emission in China.

Although widely recognized as the key to climate goals, coal "phase down" has long been argued for its side effects on energy security and social development. Retrofitting coal power units with biomass and coal co-firing with a carbon capture and storage approach provides an alternative way to avoid these side effects and make deep carbon dioxide emission cuts or even achieve negative emission. However, there is a lack of clear answers to how much the maximum emission reduction potential this approach can unlock, which is the key information to promote this technology on a large scale. Here, we focus on helping China's 4536 coal power units make differentiated retrofit choices based on unit-level heterogeneity information and resource spatial matching results. We found that China's coal power units have the potential to achieve 0.4 Gt of negative CO2 emission in 2025, and the cumulative negative CO2 emission would reach 10.32 Gt by 2060. To achieve negative CO2 emission, the biomass resource amount should be 1.65 times the existing agricultural and forestry residues, and the biomass and coal co-firing ratio should exceed 70%. Coal power units should grasp their time window; otherwise, the maximum negative potential would decrease at a rate of 0.35 Gt per year.

Size-segregated particle number concentrations and outpatient-department visits for pediatric respiratory diseases in Shanghai, China.

BACKGROUND: Few studies have simultaneously explored which size of particles has the greatest impact on the risk for pediatric asthma, bronchitis and upper respiratory tract infections (URTIs). OBJECTIVES: To investigate the short-term association between size-segregated particle number concentrations (PNCs) and outpatient-department visits (ODVs) for major pediatric respiratory diseases. METHODS: Daily counts of pediatric ODVs for asthma, bronchitis and URTIs were obtained from 66 hospitals in Shanghai, China, from 2016 to 2018. Pollutant effects were estimated using Poisson generalized additive models combined with polynomial distributed lag models. We also fitted co-pollutant cumulative effects models included six criteria air pollutants and conducted stratifying analyses by gender, age, season and geographic distances. RESULTS: We identified a total of 430,103 patients with asthma, 1,547,013 patients with bronchitis, and 2,155,738 patients with URTIs from the hospitals. Effect estimates increased with decreasing particle size. Ultrafine particle (UFP) and PNCs of 0.10-0.40 µm particles (PNC0.10-0.40) were associated with increased ODVs for asthma, bronchitis and URTIs at cumulative lags up to 3d. Associations tended to appear stable after adjusting for criteria air pollutants. At the cumulative lag 0-2d, each interquartile range increase in UFP was associated with increased ODVs due to asthma (relative risk 1.21, 95% CI: 1.07, 1.38), bronchitis (1.20, 95% CI: 1.07, 1.34) and URTI (1.17, 95% CI: 1.06, 1.30), whereas the associations for PNC0.10-0.40 remained significant but attenuated in magnitude. CONCLUSIONS: UFP may be a leading contributor to the adverse respiratory effects of particulate air pollution and the effects increased with decreasing particle size.

A study of the relationship between human infection with avian influenza a (H5N6) and environmental avian influenza viruses in Fujian, China.

BACKGROUND: Avian influenza A (H5N6) virus poses a great threat to the human health since it is capable to cross the species barrier and infect humans. Although human infections are believed to largely originate from poultry contaminations, the transmissibility is unclear and only limited information was available on poultry environment contaminations, especially in Fujian Province. METHODS: A total of 4901 environmental samples were collected and tested for Avian Influenza Virus (AIV) from six cities in Fujian Province through the Fujian Influenza Surveillance System from 2013 to 2017. Two patient-related samples were taken from Fujian's first confirmed H5N6 human case and his backyard chicken feces in 2017. Chi-square test or Fisher's exact probability test was used to compare the AIV and the viral subtype positive rates among samples from different Surveillance cities, surveillance sites, sample types, and seasons. Phylogenetic tree analysis and molecular analysis were conducted to track the viral transmission route of the human infection and to map out the evolutions of H5N6 in Fujian. RESULTS: The overall positive rate of the H5 subtype AIVs was 4.24% (208/4903). There were distinctive differences (p < 0.05) in the positive rates in samples from different cities, sample sites, sample types and seasons. The viruses from the patient and his backyard chicken feces shared high homologies (99.9-100%) in all the eight gene segments. Phylogenetic trees also showed that these two H5N6 viruses were closely related to each other, and were classified into the same genetic clade 2.3.4.4 with another six H5N6 isolates from the environmental samples. The patient's H5N6 virus carried genes from H6N6, H5N8 and H5N6 viruses originated from different areas. The R294K or N294S substitution was not detected in the neuraminidase (NA). The S31 N substitution in the matrix2 (M2) gene was detected but only in one strain from the environmental samples. CONCLUSIONS: The H5 subtype of AIVs has started circulating in the poultry environments in Fujian Province. The patient's viral strain originated from the chicken feces in his backyard. Genetic reassortment in H5N6 viruses in Fujian Province was indicated. The H5N6 viruses currently circulating in Fujian Province were still commonly sensitive to Oseltamivir and Zanamivir, but the resistance against Amantadine has emerged.

Fragment-wise design of inhibitors to 3C proteinase from enterovirus 71.

BACKGROUND: Enterovirus 71 (EV71) is a causative agent of hand, foot and mouth disease (HFMD), which can spread its infection to central nervous and other systems with severe consequence. A key factor in the replication of EV71 is its 3C proteinase (3C(pro)), a significant drug target. Peptidomimetics were employed as inhibitors of this enzyme for developing antivirals. However, the peptide bonds in these peptidomimetics are a source of low bioavailability due to their susceptibility to protease digestion. To produce non-peptidomimetic inhibitors by replacing these peptide bonds, it would be important to gain better understanding on the contribution of each component to the interaction and potency. METHODS: A series of compounds of different lengths targeting 3C(pro) and having an α,ß-unsaturated ester as the warhead were synthesized and their interactions with the enzyme were evaluated by complex structure analyses and potency assays for a better understanding on the relationship between potency and evolution of interaction. RESULTS: The P2 moiety of the compound would need to be oriented to interact in the S2 site in the substrate binding cleft and the P3-P4 moieties were required to generate sufficient potency. A hydrophobic terminal group will benefit the cellular uptake and improve the activity in vivo. CONCLUSIONS AND GENERAL SIGNIFICANCE: The data presented here provide a basis for designing a new generation of non-peptidomimetics to target EV71 3C(pro).

Epidemiology and etiology of hand, foot, and mouth disease in Fujian province, 2008-2014.

Millions of cases of hand, foot, and mouth disease (HFMD) have been reported annually in mainland China since 2008. In this study, we investigated the epidemiology and etiology of an HFMD epidemic in Fujian province, which is located in subtropical southeastern China. Our study found similar epidemiological features of HFMD in southern areas of China, including seasonality and demographic distribution, as well as correlation between severity of illness and serotype. At least 22 serotypes of other enterovirus co-circulating with enterovirus 71 were found to belong to clade C4a, and those circulating with coxsackievirus A16 were associated with clades B1a and B1b.

Serotyping and Genetic Characterization of Hand, Foot, and Mouth Disease (HFMD)-Associated Enteroviruses of No-EV71 and Non-CVA16 Circulating in Fujian, China, 2011-2015.

BACKGROUND Hand, foot, and mouth disease (HFMD) is a common contagious disease in infants; it is caused by multiple serotypes of human enterovirus (EV), which belongs to the enterovirus genus of the picornavirus family. According to sentinel surveillance, infection with EVs other than EV71 and CVA 16 have become increasingly common in recent years among HFMD patients, posing new challenges for HFMD control. This study aimed to explore the spectrum of serotypes in the other EVs (non-EV71 and non-CVA16) in Fujian province in southeastern China. MATERIAL AND METHODS We investigated 562 samples from EVs-infected HFMD patients with diagnosis confirmed by real-time RT-PCR with other EVs infection between 2011 and 2015. Nucleotide acid detection and the serotyping of the enteroviruses were also performed. The complete VP1 gene was amplified and sequenced. VP1-based phylogenetic analyses of CVA6, CVA10, CVA4, and CVA2 were also performed. RESULTS Among the samples, 22 serotypes of the other EVs, which belong to 4 species of human enterovirus A-D, were identified. Of the 22 serotypes, CVA6 (57.8%) and CVA10 (21.0%) were most common, followed by CVA4 (6.8%) and CVA2 (2.7%). The other 18 serotypes accounted for 11.7% of samples, none of which exceeded 2%. Among 47 (8.4%) samples from patients with severe HFMD, 10 serotypes were identified and most samples belonged to CVA6 (20/47), followed by CVA10 (11/47). Entire VP1 comparison revealed that overall genetic identities were 96.7%, 96.3%, 94.4%, and 94.9% among strains within CVA6, CVA10, CVA4, and CVA2, respectively. CONCLUSIONS VP1-based phylogenetic analysis for the 4 predominant serotypes indicated various clades or sub-clades, which suggests the complex transmissions of other enteroviruses in Fujian.

[Clinical characteristics of hospitalized severe acute respiratory illnesses (SARI) in children and risk factors analysis of severe illness: results from SARI patients under 15-year-old of sentinel surveillance in 10 cities, China].

OBJECTIVE: To investigate clinical and epidemiological characteristics of hospitalized severe acute respiratory illnesses (SARI) patients under 15 years old registered by sentinel hospitals at 10 cities and risk factors analysis of severe illness. METHODS: The objects of this study were 2 937 SARI patients under 15 years old registered by sentinel surveillance in internal wards, pediatrics wards and intensive care units (ICU) of 10 sentinel hospitals in 10 cities during the period from December 2009 to June 2014. We also collected case report form (CRF) of them and their throat swabs for influenza testing. The inclusion criteria was hospitalized patients who were admitted by surveillance departments, registered by SARI surveillance system, under 15 years old, meeting SARI case definition and with complete CRF. Rank-sum test was used to compare the difference of age, the duration including from onset to admission, hospital stay and from onset to discharging/death between mild illness and severe illness. Chi-square test was used to compare the difference of demographic characteristics, influenza psoitive rate, vaccination rate of influenza, chronic medical conditions and clinical characteristics between mild illness and severe illness. Logistic regression was used to analysis risk factors associated with severe illness by two stratifications from SARI surveillance protocol (< 2 years old and ≥ 2 years old). RESULTS: Among 2 937 SARI patients under 15 years old, 97.7% (2 872/2 937) was mild illnesses, and 2.3% (65/2 937) was severe illnesses. 78.8% (2 315/2 937) was under 5 years old. The median ages of severe illness and mild illness were 0.4 and 2.0 years old (U = -6.23, P < 0.001). The proportions of severe illness and mild illness with at least one chronic medical condition were 32.3% (21/65) and 8.4% (240/2 872) (χ² = 45.03, P < 0.001). The positive rate of influenza virus was 6.5% (190/2 937), which was 6.5% (186/2 858) for mild illness and 6.2% (4/65) for severe illness (χ² = 0.08, P = 0.961). The proportion of seasonal influenza vaccination was 1.5% (42/2 853), which was 1.5% (42/2 788) for mild illness and higher than that for severe illness (0) (χ² = 6.09, P = 0.048). For under 2 years old patients, age < 11 months and with at least one chronic medical condition were risk factors for severe SARI illness, and the risk for SARI patients who was 12-23 months and without medical condition was 14.71 (5.35-40.44) and 5.61 (2.96-10.63). For ≥ 2 years old patients, age, with at least one chronic medical condition and seasonal influenza vaccination history have no association with severe illness, OR (95% CI) was 0.92 (0.80-1.05), 0.67 (0.09-5.05) and 0.85 (0.31-2.35), respectively. CONCLUSION: Most of SARI patients registered by 10 urban sentinel hospitals were patients under 5 years old. Age < 11 months and with at least chronic medical conditions were possible risk factors of severe illness of SARI patients.

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.

Genome analysis of human respiratory syncytial virus in Fujian Province, Southeast China.

BACKGROUND: Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. Reports on RSV in China are limited, especially in Fujian Province, and RSV whole-genome sequences in Fujian Province are not reported. This study aimed to explore the genomic characteristics of RSV to provide evidence for the development of vaccines and medicines. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify and obtain the attachment (G) gene and whole-genome fragments from the positive samples. Genetic evolution as well as nucleotide and amino acid homology analyses of the virus sequences were conducted to identify any amino acid mutations. RESULTS: A total of 72 RSV-positive cases were collected, and 53 G gene sequences were obtained using polymerase chain reaction (PCR) amplification. The ON1 and BA11 genotypes were found to be dominant using the Basic Local Alignment Search Tool (BLAST) on the NCBI website. The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. Compared to the ON1 prototype (JN257693) and BA11 prototype (AY333364), the obtained sequences had no nucleotide insertions or deletions, indicating high similarity among the samples. A total of 17 RSV whole genome sequences were obtained, 10 of which were genotype ON1 and seven were genotype BA11. Certain amino acid mutations were found in the antigen site and epitope of the fusion (F) protein but not in the G protein. Glycosylation analyses of specific RSV genes revealed high positive selection rates for the gene, and the N- and O-linked glycosylation sequences in the F gene were relatively conserved. CONCLUSIONS: From July 2018 to January 2020, ON1 and BA11 were the most prevalent RSV genotypes in Fujian Province. A high nucleotide identity and amino acid similarity were observed between the reference strain and the obtained strains, as well as among the sequences of the obtained isotypes. Certain amino acid mutations occur at the antigen site and the epitope of the F protein.

A rule-based method to downscale provincial level power sector projection results to plant level.

Usually, previous studies on the future development pathway of coal power are based on the economic models to provide the administrative pathways, or the coal-fired power plants dataset to provide bottom-up pathways with the multi-scenario hypothesis. However, these two methods above are difficult to be combined: there is a gap between the comprehensive consideration of economic, policy, and environmental factors, with the high spatial resolution of technology and space. This study narrows the gap between regional projection and unit data, and also considers the uncertainty of the operating units with the Monte Carlo Method. Firstly, we evaluate the score of each unit according to its technical parameters and other attribute information, which is based on a sufficient dataset of coal-fired power units with their geographical spatial coordinates. And next, the probability distribution function is built according to the scores of the candidate units. Then, we do sampling from the candidate units until the total capacity reaches the regional projection of the coal power development goal. Based on this method, we could identify the spatial distribution probability of coal-fired power units in the future, and therefore it can help us explore the environmental impacts in high-resolution space.•The method calculates the probability of operating status of candidate units using technical and attribute information-base scores with Monte Carlo method.•This paper describes the uncertainties in determining the spatial distribution of future power plants, and verifies the robustness of the results.•This method narrows the scale gap between regional projection and unit-level data.

Incorporating health co-benefits into technology pathways to achieve China's 2060 carbon neutrality goal: a modelling study.

BACKGROUND: The announcement of China's 2060 carbon neutrality goal has drawn the world's attention to the specific technology pathway needed to achieve this pledge. We aimed to evaluate the health co-benefits of carbon neutrality under different technology pathways, which could help China to achieve the carbon neutrality goal, air quality goal, and Healthy China goal in a synergetic manner that includes health in the decision-making process. METHODS: In this modelling study, we used Shared Socioeconomic Pathway 2 with no climate policy as the reference scenario, and two representative carbon neutrality scenarios with identical emission trajectories and different technology pathways-one was led by renewable energies and the other was led by negative emission technologies. We had three modules to analyse health co-benefits and mitigation costs for each policy scenario. First, we used a computable general equilibrium model that captures the operation of the whole economic system to investigate the carbon mitigation costs and air pollutant emission pathways of different technology portfolios. Second, we used a reduced complexity air quality model to estimate the concentrations of particulate matter in the atmosphere from the air pollutant emission pathways. Finally, we used a health impact evaluation model to estimate premature deaths, morbidity, and the resulting loss of life expectancy, then these health impacts were monetised according to value of a statistical life and cost of illness. We compared the monetised health co-benefits against the corresponding mitigation costs to explore the cost-effectiveness of different technology portfolios. A series of uncertainties embodied in carbon neutrality pathways and models were considered. FINDINGS: In our models, sole dependence on improving end-of-pipe air pollution control measures is not sufficient for all Chinese provinces to meet the 2005 WHO PM2·5 standards (10 µg/m3) by 2060. Only a combination of strong climate and air pollution control policies can lead to substantial improvement of air quality across China. If the carbon neutrality pathway led by developing renewable energies was followed, the air quality of all provinces could meet the WHO guideline by 2060. With the realisation of carbon neutrality goals, the total discounted mitigation costs (discount rate 5%) from 2020-60 would range from 40-125 trillion Chinese yuan (CNY), and 22-50 million cumulative premature deaths could be avoided. China has the potential to increase the associated life expectancy by 0·88-2·80 years per person in 2060 versus the reference scenario. The health benefits are higher in the renewable energies-led scenarios, whereas the mitigation costs are smaller in the negative emission technologies-led scenarios. If the value of a statistical life is set higher than 12·5 million CNY (39% of the Organisation for Economic Co-operation and Development value), the health co-benefits will be higher than mitigation costs, even when considering all included uncertainties, implying the cost-effectiveness of China's carbon neutrality goal. INTERPRETATION: The life expectancy increase from the realisation of China's 2060 carbon neutrality goal could be equivalent to the past 5-10 years of life expectancy growth in China. Choosing an appropriate carbon neutrality pathway affects the health of China's population both today and in the future. Our findings suggest that, if China incorporates health co-benefits into climate policy making and puts a high value on people's health, it should choose a carbon neutrality pathway that relies more on developing renewable energies and avoid over-reliance on negative emission technologies. FUNDING: National Key R&D Program of China, National Natural Science Foundation of China, Tsinghua-Toyota Joint Research Fund, Tsinghua-Rio Tinto Joint Research Centre for Resources, and Global Energy Interconnection Group. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

The epidemiological characteristics of dengue in high-risk areas of China, 2013-2016.

INTRODUCTION: Dengue has become a more serious human health concern in China, with increased incidence and expanded outbreak regions. The knowledge of the cross-sectional and longitudinal epidemiological characteristics and the evolutionary dynamics of dengue in high-risk areas of China is limited. METHODS: Records of dengue cases from 2013 to 2016 were obtained from the China Notifiable Disease Surveillance System. Full envelope gene sequences of dengue viruses detected from the high-risk areas of China were collected. Maximum Likelihood tree and haplotype network analyses were conducted to explore the phylogenetic relationship of viruses from high-risk areas of China. RESULTS: A total of 56,520 cases was reported in China from 2013 to 2016. During this time, Yunnan, Guangdong and Fujian provinces were the high-risk areas. Imported cases occurred almost year-round, and were mainly introduced from Southeast Asia. The first indigenous case usually occurred in June to August, and the last one occurred before December in Yunnan and Fujian provinces but in December in Guangdong Province. Seven genotypes of DENV 1-3 were detected in the high-risk areas, with DENV 1-I the main genotype and DENV 2-Cosmopolitan the secondary one. The Maximum Likelihood trees show that almost all the indigenous viruses separated into different clusters. DENV 1-I viruses were found to be clustered in Guangdong Province, but not in Fujian and Yunnan, from 2013 to 2015. The ancestors of the Guangdong viruses in the cluster in 2013 and 2014 were most closely related to strains from Thailand or Singapore, and the Guangdong virus in 2015 was most closely related to the Guangdong virus of 2014. Based on closest phylogenetic relationships, viruses from Myanmar possibly initiated further indigenous cases in Yunnan, those from Indonesia in Fujian, while viruses from Thailand, Malaysia, Singapore and Indonesia were predominant in Guangdong Province. CONCLUSIONS: Dengue is still an imported disease in China, although some genotypes continued to circulate in successive years. Viral phylogenies based on the envelope gene suggested periodic introductions of dengue strains into China, primarily from Southeast Asia, with occasional sustained, multi-year transmission in some regions of China.

Excretion of SARS-CoV-2 through faecal specimens.

Coronavirus disease 2019 (COVID-19) has become a pandemic with increasing numbers of cases worldwide. SARS-CoV-2, the causative virus of COVID-19, is mainly transmitted through respiratory droplets or through direct and indirect contact with an infected person. The possibility of potential faecal-oral transmission was investigated in this study. We collected 258 faecal specimens from nine provinces in China and detected the nucleic acid of SARS-CoV-2 using real-time RT-PCR. Vero cells were used to isolate the virus from SARS-CoV-2 nucleic acid positive samples, after which sequencing of Spike gene in eight samples was performed. In all, 93 of 258 (36%) stool samples were positive for SARS-CoV-2 RNA. The positive rates of critical, severe, moderate, and mild patients were 54.4%, 56.1%, 30.8%, and 33.3%, respectively. The content of nucleic acid increased within 2 weeks after the onset of the disease. From the perspective of clinical typing, the nucleic acid can be detected in the faeces of critical patients within two weeks and until four to five weeks in the faeces of severe and mild patients. SARS-CoV-2 was isolated from stool specimens of two severe patients. Four non-synonymous mutations in Spike gene were newly detected in three stool samples. A small number of patients had strong faecal detoxification ability. The live virus in faeces could be an important source of contamination, which may lead to infection and further spread in areas with poor sanitary conditions. The findings of this study have public health significance and they should be considered when formulating disease control strategies.

Emergence of waterfowl-originated gene cassettes in HPAI H7N9 viruses caused severe human infection in Fujian, China.

BACKGROUND: Highly pathogenic avian influenza (HPAI) A(H7N9) virus emerged and caused human infections during the 2016-2017 epidemic wave of influenza A(H7N9) viruses in China. We report a human infection with HPAI H7N9 virus and six environmental isolates in Fujian Province, China. METHODS: Environmental surveillance was conducted in live poultry markets and poultry farms in Fujian, China. Clinical and epidemiologic data and samples were collected. Real-time RT-PCRs were conducted for each sample, and H7-positive samples were isolated using embryonated chicken eggs. Full genomes of the isolates were obtained by next-generation sequencing. Phylogenetic analysis and antigenic analysis were conducted. RESULTS: A 59-year-old man who raised about 1000 ducks was identified as HPAI H7N9 infection. Six HPAI H7 viruses were isolated from environmental samples, including five H7N9 viruses and one H7N6 virus. Phylogenetic results showed the human and environmental viruses are highly genetically diverse and containing significantly different gene constellation from that of other HPAI H7N9 previously reported. The internal genes derived from H7N9/H9N2, H5N6, and the Eurasian wild-bird gene pool, indicating waterfowl-originated genotypes, have emerged in HPAI H7N9/N6 viruses and caused human infection. CONCLUSION: The new genotypes raise the concern that these HPAI H7 viruses might transmit back into migratory birds and spread to other countries as the HPAI H5Nx viruses. Considering their capability of causing severe infections in both human and poultry, the HPAI H7 viruses in this study pose a risk to public health and the poultry industry and highlight the importance of sustained surveillance of these viruses.

High-level expression of recombinant dengue virus type 2 envelope domain III protein and induction of neutralizing antibodies in BALB/C mice.

Dengue fever is a growing public health problem in many countries since so far no effective vaccines are available. In this study, the domain III of dengue virus type 2 envelope was expressed in Escherichia coli without fusion of any carrier protein. The recombinant protein was detected in the form of inclusion bodies, which were solubilized in 8M urea and could be purified subsequently by high-performance liquid chromatography (HPLC) on an ion exchange column. After refolding, the recombinant protein inhibited the DEN-2 plaque formation on C6/36 cells, demonstrated its function of receptor-interaction was retained. The recombinant protein was inoculated into BALB/c mice to test its immunogenicity and ability to induce neutralizing antibodies. The mice immunized with the purified protein developed high antibody titers. A neutralizing titer of 1:64 was also obtained by a cytopathogenic effect (CPE) inhibition assay in C6/36 cells. Mice challenged with lethal dose of DEN-2 in combination with sera from immunized mice were protected completely. The results suggested that these expression and purification strategies have the potential for development of an inexpensive vaccine.

Epidemiological and etiological investigation of dengue fever in the Fujian province of China during 2004-2014.

Dengue fever (DF) is a vector-borne disease and a tremendous socioeconomic burden on tropical and subtropical countries worldwide. To explore the characteristics of DF epidemic in the Fujian province, information of DF cases in Fujian during 2004-2014 was collected and analyzed. The complete E genes of 48 viral isolates were amplified and sequenced for phylogenetic analysis. A total of 733 cases was reported, of which 612 (83.5%) occurred during the peak period from August to October. Additionally, 76% (190/250) of imported cases originated from Southeast Asia countries, by the epidemiological investigation. Phylogenetic analysis of the 48 viral isolates revealed that three genotypes (I, IV, V) of DENV1, and one genotype each of DENV2 (cosmopolitan) and DENV3 (I) circulated in Fujian during 2004-2014. Similar to the results of the epidemiological investigations, the source of most of the viral isolates, including imported and indigenous cases, may be Southeast Asia countries; however, importation from adjacent provinces was also observed in recent years. Overall, DF is considered an imported epidemic disease in Fujian. Increasing diversity of the viral source and geographic expansion of the area affected by DF in recent years highlights the necessity for strengthening surveillance of the DF epidemic and developing strategies for DF prevention and control in Fujian.

Epidemiological, clinical, and virologic features of two family clusters of avian influenza A (H7N9) virus infections in Southeast China.

This study aimed to investigate the epidemiological, clinical, and virologic characteristics of avian influenza A (H7N9) confirmed cases from two family clusters in Southeast China. Epidemiological data of the H7N9 confirmed cases and their close contacts were obtained through interviews and reviews of medical records. Of the four patients in these two family clusters, two cases had mild symptoms, one had severe symptoms, and one died. Three of the four patients had a history of exposure to live poultry or contaminated environments. The complete genome sequences of the H7N9 viruses from the same family cluster were highly homologous, and the four isolated viruses from the two family clusters exhibited the virologic features of the H7N9 virus, in terms of transmissibility, pathogenicity, host adaptation, and antiviral drug resistance. In addition, our findings indicated that the A/Fujian/18/2015 viral strain contained an additional hemagglutinin G225D substitution, which preferentially binds α2,6-linked sialic acids. The results of this study demonstrate that one family cluster was infected through common exposure to live poultry or contaminated environments, and the other was more likely to be infected through the human-to-human route.

[Role of syndromic surveillance program in the practice of early detection on disease outbreak].

OBJECTIVE: A Dengue outbreak was reported in Dongfen town Jianou county, Fujian province on September 19, 2014. The goal of this project was to explore the role of syndromic surveillance program in the practice of early detection on disease outbreak through the case mentioned above. METHODS: The authors retrospectively collected data related to Outpatient log and Pharmacy drug use in Dongfen township hospital through the electronic information system of the hospital from August to November, 2014. All the abnormal events were recorded, according to related data on fever and drug use. Description of fever, syndromic characteristics, correlation and Linear regression analyses were conducted, using the surveillance data on fever syndrome and drug use from the pharmacy. RESULTS: A total of 1 102 cases with fever and 2 437 fever-related clinic visits were reported which showing an increased number of 19.6, 10.2 times respectively, when compared to the same period of the previous year in which men accounted for 45.3% (499/1 102) and female accounted for 54.7% (603/1 102). Age groups presented an atypical type " M" type. 5 and 10 year olds groups formed the largest proportion, accounted for 11.5% (127/1 102) of the total number os the patients. The correlation coefficient ranged from 0.85 to 0.97 (P<0.05). Data from the syndromic surveillance program showed an " outbreak" was occured in August 23, 2014. CONCLUSIONS: Compared to routine surveillance program, the syndromic surveillance program could detect the appearence of an outbreak, a month or even more earlier. The role of syndromic surveillance program needs to be further explored.

[Molecular epidemiology of hand-foot-mouth disease associated pathogen Coxsackievirus A10 identified in Fujian province, 2011-2014].

OBJECTIVE: To study the molecular epidemiology of hand-foot-mounth disease (HFMD) associated Coxsackievirus A10 (Cox A10) identified in Fujian province. METHODS: A total of 1 525 specimens from non-EV71 non-Cox A16 HFMD patients were collected during 2011-2014. Isolated virus strains were identified and sub-typed. Full-length coding regions for the VP1 gene of the predominant serotype Cox A10 isolates were amplified and sequenced. RESULTS: Among the 407 non-EV71 non-Cox A16 HFMD cases confirmed by virus isolation and molecular subtyping, 103 (25.3%) were caused by Cox A10, accounting for 11.0%, 6.0%, 18.4% and 9.2% among the HFMD-associated entero-viruses identified in 2011, 2012, 2013 and 2014, respectively, in Fujian province. Compared to the general features observed in the HFMD epidemics, no differences on the Cox A10-specificity rates were observed among factors as geographical origins, gender or age groups, but all with high rates of severity. Data from the nucleotide sequence analyses on VP1 genes showed low homology levels of 76.0%-77.1% among Cox A10 strains from Fujian province, in contrast to the prototype Cox A10 strain, but with high levels of homology in the amino acid sequences (91.9%-93.6%). RESULTS from the Phylogenetic analysis also indicated that Cox A10 isolates from Fujian province were distinct from the prototype strain or other isolates from other countries but was homologous to domestic strains, but the Fujian isolates clustered into multiple branches. CONCLUSIONS: Cox A10 remained one of the predominant serotypes of HFMD in Fujian province. Cox A10 isolates identified in Fujian province were co-circulating and co-evolving with other domestic strains.