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Abstract Metaphor processing has been the subject of extensive research over the past five decades. A systematic review of metaphor processing publications through bibliometric tools can provide a clear overview of research on metaphor processing. In this study, we used the CiteSpace bibliometric tool to conduct a systematic review of publications related to metaphor processing. A total of 3271 works published and indexed in the Web of Science (WoS) were gathered. These works had been published between 1970 and 2022. We analyzed the co-citations of these works by CiteSpace to identify the most influential publications in metaphor processing research. A co-occurrence term analysis was done to identify dominant topics in this area of research. The results of this analysis showed that Language, comprehension, metaphor, figurative language, and context were the most frequent keywords. The most prominent clusters were students, figurative language, right hemisphere, embodied cognition, comprehension, N400, and anger. Based on the results of this analysis, we suggest that task properties such as response format and linguistic features should be carefully taken into account in future studies on metaphor processing.

Abstract Background Mild hand, foot and mouth disease (HFMD) cases make up a relatively high proportion of HFMD while have often been overlooked. This study aimed to investigate the epidemiological and etiological characteristics of mild HFMD in Nanjing. Methods Data on mild HFMD cases, during 2010–2019 in Nanjing, were collected from the China Information System for Disease Control and Prevention. This study mainly focused on mild cases aged

Previous studies have examined WATER metaphors in different discourses, yet there has been limited focus on understanding the functions of these metaphors in constructing discourses. To address this research gap, the present paper utilised the metaphor identification procedure developed by the Pragglejaz Group and the Weak Differentiating Model to investigate WATER metaphors in the Coronavirus Corpus. The study reveals that WATER metaphors can be used flexibly for multiple purposes. These include explaining the many pandemic stages, describing the occurrence and performance of the pandemic, explaining how COVID-19 affects human life, rallying the public to take precautions against contagion, and communicating risk. This research highlights the diverse functions that WATER metaphors served in conveying intricate information and influencing public perceptions throughout the COVID-19 pandemic.

BackgroundGlycolysis and cholesterol synthesis are crucial in cancer metabolic reprogramming. The aim of this study was to identify a glycolysis and cholesterol synthesis-related genes (GCSRGs) signature for effective prognostic assessments of osteosarcoma patients.MethodsGene expression data and clinical information were obtained from GSE21257 and TARGET-OS datasets. Consistent clustering method was used to identify the GCSRGs-related subtypes. Univariate Cox regression and LASSO Cox regression analyses were used to construct the GCSRGs signature. The ssGSEA method was used to analyze the differences in immune cells infiltration. The pRRophetic R package was utilized to assess the drug sensitivity of different groups. Western blotting, cell viability assay, scratch assay and Transwell assay were used to perform cytological validation.ResultsThrough bioinformatics analysis, patients diagnosed with osteosarcoma were classified into one of 4 subtypes (quiescent, glycolysis, cholesterol, and mixed subtypes), which differed significantly in terms of prognosis and tumor microenvironment. Weighted gene co-expression network analysis revealed that the modules strongly correlated with glycolysis and cholesterol synthesis were the midnight blue and the yellow modules, respectively. Both univariate and LASSO Cox regression analyses were conducted on screened module genes to identify 5 GCSRGs (RPS28, MCAM, EN1, TRAM2, and VEGFA) constituting a prognostic signature for osteosarcoma patients. The signature was an effective prognostic predictor, independent of clinical characteristics, as verified further via Kaplan-Meier analysis, ROC curve analysis, univariate and multivariate Cox regression analysis. Additionally, GCSRGs signature had strong correlation with drug sensitivity, immune checkpoints and immune cells infiltration. In cytological experiments, we selected TRAM2 as a representative gene to validate the validity of GCSRGs signature, which found that TRAM2 promoted the progression of osteosarcoma cells. Finally, at the pan-cancer level, TRAM2 had been correlated with overall survival, progression free survival, disease specific survival, tumor mutational burden, microsatellite instability, immune checkpoints and immune cells infiltration.ConclusionTherefore, we constructed a GCSRGs signature that efficiently predicted osteosarcoma patient prognosis and guided therapy.

Existing research on syntactic complexity tends to examine diversity and complexity embedded in grammatical employments which may well be witnessed in formulations of different syntactic structures. Conceivably, the subject syntactic complexity seems to be exercised mostly by non-native speakers and writers. The present study employs pseudo-longitudinal data: essays written by undergraduate students in different levels collected at the same time. Hence, it aims at investigating the mechanism involved in the L2 production of L2 learners in terms of syntactic complexity by analyzing a corpus of non-native English-speaking learners. The research inquiry is mainly focused on investigation of significant differences in terms of syntactic complexity between writing of Japanese university students and that of native speakers, probing further into the particular dimension and level of difference. The study also traces marked variations in syntactic complexity employed by Japanese university students in different grades. Nagoya Interlanguage Corpus of English (NICE) developed by Sugiura in 2015 was employed to conduct the entire research proceedings. The corpus of the subject study comprises 339 essays written by L2 EFL learners studying in a Japanese university employing a judicious selection of quantitative measures of syntactic complexity. The results exhibited a considerable statistical difference between the writing of Japanese learners and native English writers. The findings of this study provide meaningful pedagogical implications for English teachers and textbook compilers. Japanese university students in higher grades are found to be employing more complicated and diverse syntactic structures. Conforming to the already conducted research studies with almost similar objectives, this study demonstrates the significance of using both general and more particular complexity metrics to assess syntactic development in L2.

Research on metaphor has gained increasing attention of world’s scholars since the publication of Lakoff and Johnson’s collaborated book Metaphors We Live By in 1980. The present study comprises a pioneering review of publications on Conceptual Metaphor Theory (CMT). It aimed to use the CiteSpace software to provide a clear overview of international research in relation to CMT. In total, 4,458 bibliometric recordings ranging from 1980 to 2022 were collected from the Web of Science (WOS) Core Collection. The descriptive analysis presents the trend of annual publications, the top 10 most prolific journals and the top 10 most productive authors. A document co-citation analysis was conducted via CiteSpace to navigate the key documents in this field. A visualization of keywords and its cluster analysis were conducted to show the research fields and dominant topics. The top 5 keywords with high frequency were language, comprehension, conceptual metaphor, discourse, and figurative language. The most prominent 5 clusters are labeled as right hemisphere, self, time, teacher education, and corpus linguistics. The present review through CiteSpace flags the need for more investigations of CMT from more aspects or interdisciplinary studies, such as metaphor translation, metaphor in literature, metaphor and corpus linguistics, etc.

Research on COVID-19 has drawn the attention of scholars around the world since the outbreak of the pandemic. Several literature reviews of research topics and themes based on scientometric indicators or bibliometric analyses have already been conducted. However, topics and themes in linguistic-specific research on COVID-19 remain under-studied. With the help of the CiteSpace software, the present study reviewed linguistic research published in SSCI and A&HCI journals to address the identified gap in the literature. The overall performance of the documents was described and document co-citations, keyword co-occurrence, and keyword clusters were visualized via CiteSpace. The main topic areas identified in the reviewed studies ranged from the influences of COVID-19 on language education, and speech-language pathology to crisis communication. The results of the study indicate not only that COVID-19-related linguistic research is topically limited but also that insufficient attention has been accorded by linguistic researchers to Conceptual Metaphor Theory, Critical Discourse Analysis, Pragmatics, and Corpus-based discourse analysis in exploring pandemic discourses and texts.

To understand influenza vaccination and its correlates among health-careworkers (HCWs) during the 2019/2020 season in China, we used a self-administeredelectronic questionnaire to collect information on demographics, occupational characteristics, influenza vaccination status and access to free vaccination on the “Breath Circles”, a Chinese media platform for respiratory medical professionals. The reported influenza vaccine coverage among HCWs during this season was 67%, with more HCWs in a workplace with free vaccination than those with no free vaccination (79% vs.34%,p < .001). The influenza vaccine coverage among HCWs who were required or encouraged to get vaccinated by the workplace was significantly higher than that without any intervention measures (80% & 70 vs.39%,p < .001). The vaccine coverage in the workplaces with free and required vaccination simultaneously was highest compared to that with neither free vaccination nor any intervention measures (OR = 14.86, 95% CI: 10.93–20.20). The influenza vaccination coverage of HCWs in high-riskdepartments was significantly higher than that of other departments (70% vs.58%,p =.023). HCWs’ vaccine coverage was related to personal opinions and attitudes toward influenza or influenza vaccines, as well as other constraints such as availability of influenza vaccines, workplace regulations, and access to free vaccines.

Background: The standard treatment for osteosarcoma comprises complete surgical resection and neoadjuvant chemotherapy, which may cause serious side effects and partial or total limb loss. Therefore, to avoid the disadvantages of traditional treatment, we developed self-assembling imageable silk hydrogels for osteosarcoma.Methods: We analysed whether iodine induced apoptosis in MG-63 and Saos-2 cells by using CCK-8 and flow cytometry assays and transmission electron microscopy. Western blotting was used to analyse the pathway of iodine-induced apoptosis in osteosarcoma cells. PEG400, silk fibroin solution, polyvinylpyrrolidone iodine (PVP-I), and meglumine diatrizoate (MD) were mixed to produce an imageable hydrogel. A nude mouse model of osteosarcoma was established, and the hydrogel was injected locally into the interior of the osteosarcoma with X-ray guidance. The therapeutic effect and biosafety of the hydrogel were evaluated.Results: Iodine treatment at 18 and 20 µM for 12 h resulted in cell survival rate reduced to 50 ± 2.1% and 50.5 ± 2.7% for MG-63 and Sao-2 cells, respectively (p < 0.01). The proportion of apoptotic cells was significantly higher in the iodine-treatment group than in the control group (p < 0.05), and apoptotic bodies were observed by transmission electron microscopy. Iodine could regulate the death receptor pathway and induce MG-63 and Saos-2 cell apoptosis. The hydrogels were simple to assemble, and gels could be formed within 38 min. A force of less than 50 N was required to inject the gels with a syringe. The hydrogels were readily loaded and led to sustained iodine release over 1 week. The osteosarcoma volume in the PEG-iodine-silk/MD hydrogel group was significantly smaller than that in the other three groups (p < 0.001). Caspase-3 and poly (ADP-ribose) polymerase (PARP) expression levels were significantly higher in the PEG-iodine-silk/MD hydrogel group than in the other three groups (p < 0.001). Haematoxylin and eosin (H&E) staining showed no abnormalities in the heart, liver, spleen, lung, kidney, pancreas or thyroid in any group.Conclusions: Self-assembling imageable silk hydrogels could be injected locally into osteosarcoma tissues with X-ray assistance. With the advantages of good biosafety, low systemic toxicity and minimal invasiveness, self-assembling imageable silk hydrogels provide a promising approach for improving the locoregional control of osteosarcoma.

Non-pharmaceutical interventions (NPIs) implemented to interrupt COVID-19 transmission may also impact the spread of other infectious diseases. Here, the authors estimate that influenza activity in China and the United States reduced by up to 80% when NPIs were in place in the 2019–2020 season.

Biomass-based carbon dots (Bio-CDs) were prepared from dehydroabietic acid using a one-step hydrothermal process. Characterization by TEM, XPS and FTIR spectroscopy showed that the Bio-CDs are spherical nanoparticles containing mainly C, N and O elements, with functional groups such as amino and carbonyl groups on their surface. The optical properties of the Bio-CDs were studied in detail. A solution of Bio-CDs exhibited excitation-dependent blue fluorescence emission. The solution showed excellent photostability under ultraviolet light and the fluorescence intensity could be enhanced by decreasing the temperature. The intensity of fluorescence emission of the solution was essentially unchanged over the pH range 3.91–8.69, and in the presence of different anions and cations, other than Fe3+ and Pb2+. Fe3+ and Pb2+ ions, respectively, quenched and enhanced the intensity of the fluorescence emission of the solution, allowing sensitive and selective detection of Fe3+ (LOD = 2.33 μM, Em = 437 nm) and of Pb2+ (LOD = 0.27 μM, Em = 437 nm and LOD = 0.33 μM, Em = 500 nm). As a further demonstration of potential applications, the Bio-CDs were shown to have low cytotoxicity and to stain cell nuclei as effectively as the commonly used nuclear stain 4′,6-diamino-2-phenylindole (DAPI), demonstrating their promise in the field of cell imaging.

Traditional haemostatic materials generally have slow hemostasis rate and poor biocompatibility. This paper reports on the haemostatic properties and mechanism of silk fibroin (SF). SF-PEG sponge that could be solubilised and changed to gel form by blood was fabricated through mixing SF and polyethylene glycol (PEG, 1500 Da) followed by lyophilisation of the mixed solution. SF-PEG sponge, together with control samples of SF sponge (no PEG) and a commercially available haemostatic material, gelatine sponge, were subjected to the hemostasis tests using a liver trauma model of rabbit. The results showed that SF was superior to gelatine sponge in hemostasis time (136.17 ± 62.27 s and 249.83 ± 29.18 s) and blood loss (2.16 ± 1.27 g vs. 4.97 ± 1.44 g). Furthermore, in vitro experiments indicated SF-PEG sol-gel transition promoted platelet adhesion and aggregation, as well as platelet-fibrinogen interaction. Therefore, except for the physical blocking of bleeding port due to PEG-induced SF fast gelation, SF might also have an impact on blood coagulation process, a phenomenon that has not been reported before. In conclusion, SF is a new type of haemostatic material that might be able to meet the requirements of speed, efficiency and biosafety in a variety of clinical applications.

Senile osteoporosis is closely related to the loss of function of stem cells. In this study, we tried to investigate the potential of secretome from human umbilical cord-derived mesenchymal stem cells (hUCMSCs) in recovering stem cell ability from senescence and then delaying bone loss. We first harvested bone marrow-derived mesenchymal stem cells (BMSCs) from young and old rats and then compared their cellular characteristics such as cell growth, anti-senescence and differentiation. The results showed that these abilities were negatively affected by animal aging. Subsequently, aged BMSCs were exposed to secretome from hUCMSCs, and we found that this loss of cell potential can be modified by secretome treatment. Thereafter, the secretome was loaded into silk fibroin-based hydrogels and used for an in vivo animal study. The results showed that compared to the old untreated group, the bone formation capacity of aged rats was improved by local treatment of secretome-loaded silk fibroin hydrogels. In conclusion, these findings demonstrated that secretome from hUCMSCs has the capacity to recover stem cell potential and delay local bone loss in age-related osteoporosis, which could potentially be applied in osteoporosis therapy in the future.

BackgroundInfluenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings.Methods and findingsWe aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996-31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle-Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20-64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%-16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000-46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000-9,432,000) LRI hospitalizations occur each year among adults. While adults ConclusionsIn this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.

Abstract Background Increasing reports demonstrated that dysregulated expression of microRNAs (miRNAs) leads to the progression of various tumors. Previous studies revealed that miR-328-3p exhibited dysregulated expression in various types of tumors. However, its function and underlying mechanism in osteosarcoma (OS) are still unexplored. Methods The expression of miR-328-3p in the tissues and OS cell lines was detected by qRT-PCR analysis. The effects of miR-328-3p in the proliferation were analyzed by MTT assay. The proliferation and apoptosis of OS cells were examined by colony formation assay and TUNEL staining respectively. The migration and tumor formation ability of OS cells were measured by wound healing assay and xenograft in vivo mice assay. Furthermore, the regulatory roles of miR-328-3p/MMP16 were determined by western blot and luciferase reporter assay. Results The expression of miR-328-3p was significantly decreased in OS tissues and cell lines. Furthermore, overexpression of miR-328-3p inhibited the cell proliferation and migration, but promoted the apoptosis of OS cells in vitro. Moreover, the analysis in vivo showed that miR-328-3p effectively suppressed the formation of tumors. According to the results of western blot analysis and luciferase reporter assay, we identified matrix metalloproteinase-16 (MMP-16) acted as a direct target of miR-328-3p. Moreover, the expression level of MMP-16, which participates in the occurrence and development of many cancers, was negatively correlated with the miR-328-3p expression in OS cells. Conclusion miR-328-3p inhibited the proliferation, migration but accelerated the apoptosis of OS by directly inhibiting MMP-16. And miR-328-3p/MMP-16 axis may be one of the mechanisms of OS development and a novel potential method for the treatment of OS in clinic.

Polymeric nanoparticles, which show aggregation-induced luminescence emission, have been successfully prepared from larch bark, a natural renewable biomass resource, in a simple, rapid ultrasonic fragmentation method. The structure, element, particle size and molecular weight distribution of larch bark extracts (LBE) were studied by FTIR, XPS, TEM, XRD and linear mode mass spectrometry, respectively. LBE was found containing large numbers of aromatic rings, displaying an average particle size of about 4.5 nm and mainly presenting tetramers proanthocyanidins. High concentration, poor solvent, low temperature and high viscosity restricted the rotation and vibration of the aromatic rings in LBE, leading to the formation of J-aggregates and enhancing the aggregation-induced fluorescence emission. LBE possessed good resistance to photobleaching under ultraviolet light (200 mW/m2). Cytotoxicity experiments for 24 h and flow cytometry experiments for 3 days proved that even the concentrations of LBE as high as 1 mg/mL displayed non-toxic to MG-63 cells. Therefore, LBE could be employed for MG-63 cell imaging, with similar nuclear staining to the DAPI. The effects of different metal ions on the fluorescence emission intensity of LBE were analyzed and exhibited that Fe3+ owned obvious fluorescence quenching effect on LBE, while other metal ions possessed little or weak effect. Furthermore, the limit of detection (LOD) of Fe3+ was evaluated as 0.17 μM.

We used national sentinel surveillance data in China for 2005–2016 to examine the lineage-specific epidemiology of influenza B. Influenza B viruses circulated every year with relatively lower activity than influenza A. B/Yamagata was more frequently detected in adults than in children.

Abstract Background Influenza disease burden varies by age and this has important public health implications. We compared the proportional distribution of different influenza virus types within age strata using surveillance data from twenty-nine countries during 1999-2014 (N=358,796 influenza cases). Methods For each virus, we calculated a Relative Illness Ratio (defined as the ratio of the percentage of cases in an age group to the percentage of the country population in the same age group) for young children (0-4 years), older children (5-17 years), young adults (18-39 years), older adults (40-64 years), and the elderly (65+ years). We used random-effects meta-analysis models to obtain summary relative illness ratios (sRIRs), and conducted meta-regression and sub-group analyses to explore causes of between-estimates heterogeneity. Results The influenza virus with highest sRIR was A(H1N1) for young children, B for older children, A(H1N1)pdm2009 for adults, and (A(H3N2) for the elderly. As expected, considering the diverse nature of the national surveillance datasets included in our analysis, between-estimates heterogeneity was high (I2>90%) for most sRIRs. The variations of countries’ geographic, demographic and economic characteristics and the proportion of outpatients among reported influenza cases explained only part of the heterogeneity, suggesting that multiple factors were at play. Conclusions These results highlight the importance of presenting burden of disease estimates by age group and virus (sub)type.

Summary: Background: The estimation of influenza-associated excess mortality in countries can help to improve estimates of the global mortality burden attributable to influenza virus infections. We did a study to estimate the influenza-associated excess respiratory mortality in mainland China for the 2010–11 through 2014–15 seasons. Methods: We obtained provincial weekly influenza surveillance data and population mortality data for 161 disease surveillance points in 31 provinces in mainland China from the Chinese Center for Disease Control and Prevention for the years 2005–15. Disease surveillance points with an annual average mortality rate of less than 0·4% between 2005 and 2015 or an annual mortality rate of less than 0·3% in any given years were excluded. We extracted data for respiratory deaths based on codes J00-J99 under the tenth edition of the International Classification of Diseases. Data on respiratory mortality and population were stratified by age group (age

The fifth epidemic wave of avian influenza A(H7N9) virus in China during 2016–2017 demonstrated a geographic range expansion and caused more human cases than any previous wave. The factors that may explain the recent range expansion and surge in incidence remain unknown. We investigated the effect of anthropogenic, poultry, and wetland variables on all epidemic waves. Poultry predictor variables became much more important in the last 2 epidemic waves than they were previously, supporting the assumption of much wider H7N9 transmission in the chicken reservoir. We show that the future range expansion of H7N9 to northern China may increase the risk of H7N9 epidemic peaks coinciding in time and space with those of seasonal influenza, leading to a higher risk of reassortments than before, although the risk is still low so far.

Myeloid derived suppressor cells (MDSC) are very important in tumor immune evasion and they dramatically increased in peripheral blood of patients with osteosarcoma cancer. The association between MDSC and various cytokines has been studied in the peripheral blood. However, little is known about the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and interleukin 18 (IL-18) level in osteosarcoma tumor model and its effect on the immunotherapy. MDSC were isolated from the blood and parenchyma and analyzed in the osteosarcoma tumor model. IL-18 levels were detected by enzyme-linked immunosorbent assay (ELISA) assay, real-time PCR, western blot and flow cytometry. Moreover, combination treatment with IL-18 inhibition and anti-PD1 was conducted to assess the therapeutic effects of IL-18 blockade. Results showed MDSC levels had a positive correlation with IL-18, suggesting IL-18 may attract MDSC into the parenchyma. IL-18 gene and protein expression significantly increased in blood and tumor lysates of tumor-bearing mice. Anti-IL-18 treatment significantly decreased G-MDSC and M-MDSC in the peripheral blood and tumor. Furthermore, combination therapy decreased the tumor burden and increased CD4+ and CD8+ T cell infiltration, as well as the production of interferon gamma (IFNγ) and granzyme B. Our study revealed a possible correlation between MDSC subsets and IL-18 inducing MDSC migration into the tumor tissue, in addition to provide the potential target to enhance the efficacy of immunotherapy in patients with osteosarcoma. Keywords: Osteosarcoma, Myeloid derived suppressor cells, Anti-PD1, IL-18

Objective This study aimed to understand the knowledge, attitudes and practices (KAP) on seasonal influenza among medical college students in a low-income multiethnic society. Methods A cross-sectional questionnaire survey collected information of KAP related to influenza. A knowledge score was calculated according to the total number of correct points out of 9 questions. Logistic regression was used to identify factors associated with influenza vaccine uptake. Results 856 valid questionnaires were obtained. The average knowledge score was 14.8 ± 3.1 out of 22 correct points. Han Chinese got higher score than minorities (p < 0.001). Knowledge score increased with grade (p < 0.001). Students majoring in pharmacy had lower score than others. Questions on mode of transmission, symptoms, precautions, high risk groups and vaccination schedule had a correct rate lower than 50%. Hand hygiene was practiced by less than 40% of students after touching objects in public areas or sneezing. The proportion of participants received influenza vaccine in the past 3 y was 4.1%, 9.2% and 6.1% respectively. Willingness to receive free vaccine (OR = 2.49, 95% CI 1.31∼4.28), and awareness of the vaccine effectiveness (OR = 1.67, 95% CI 1.08∼2.56) were significantly associated with vaccine uptake, while the general knowledge about influenza, perceived susceptibility and severity, and demographic factors were not. The top 3 reasons for not being vaccinated were poor knowledge of the vaccine (46%), no perceived need due to good health (45%) and worry about adverse reactions (33%). Conclusion Health education is needed to improve the awareness of basic facts about influenza and vaccine, and more attention should be paid to minority groups. The coverage of seasonal influenza vaccine is quite low. Besides individual level behavior change, social and structural factors should be considered to increase the uptake of influenza vaccine.

We describe the epidemiological characteristics, pattern of circulation, and geographical distribution of influenza B viruses and its lineages using data from the Global Influenza B Study. We included over 1.8 million influenza cases occurred in thirty-one countries during 2000-2018. We calculated the proportion of cases caused by influenza B and its lineages; determined the timing of influenza A and B epidemics; compared the age distribution of B/Victoria and B/Yamagata cases; and evaluated the frequency of lineage-level mismatch for the trivalent vaccine. The median proportion of influenza cases caused by influenza B virus was 23.4%, with a tendency (borderline statistical significance, p = 0.060) to be higher in tropical vs. temperate countries. Influenza B was the dominant virus type in about one every seven seasons. In temperate countries, influenza B epidemics occurred on average three weeks later than influenza A epidemics; no consistent pattern emerged in the tropics. The two B lineages caused a comparable proportion of influenza B cases globally, however the B/Yamagata was more frequent in temperate countries, and the B/Victoria in the tropics (p = 0.048). B/Yamagata patients were significantly older than B/Victoria patients in almost all countries. A lineage-level vaccine mismatch was observed in over 40% of seasons in temperate countries and in 30% of seasons in the tropics. The type B virus caused a substantial proportion of influenza infections globally in the 21st century, and its two virus lineages differed in terms of age and geographical distribution of patients. These findings will help inform health policy decisions aiming to reduce disease burden associated with seasonal influenza.

Influenza endangers human health but can be prevented in part by vaccination. Assessing influenza vaccine effectiveness (VE) provides scientific evidence for developing influenza vaccination policy. We conducted a systematic review and meta-analysis of studies that evaluated influenza VE in mainland China. We searched six relevant databases as of 30 August 2019 to identify studies and used Review Manager 5.3 software to analyze the included studies. The Newcastle–Ottawa scale was used to assess the risk of publication bias. We identified 1408 publications, and after removing duplicates and screening full texts, we included 21 studies in the analyses. Studies were conducted in Beijing, Guangzhou, Suzhou, and Zhejiang province from the 2010/11 influenza season through the 2017/18 influenza season. Overall influenza VE for laboratory confirmed influenza was 36% (95% CI: 25–46%). In the subgroup analysis, VE was 45% (95% CI: 18–64%) for children 6–35 months who received one dose of influenza vaccine, and 57% (95% CI: 50–64%) who received two doses. VE was 47% (95% CI: 39–54%) for children 6 months to 8 years, and 18% (95% CI: 0–33%) for adults ≥60 years. For inpatients, VE was 21% (95% CI: −11–44%). We conclude that influenza vaccines that were used in mainland China had a moderate effectiveness, with VE being higher among children than the elderly. Influenza VE should be continuously monitored in mainland China to provide evidence for policy making and improving uptake of the influenza vaccine.

Since March 2013, a novel influenza A(H7N9) virus has caused 3 epidemic waves of human infection in mainland China. We analyzed data from patients with laboratory-confirmed influenza A(H7N9) virus infection to estimate the risks for severe outcomes after hospitalization across the 3 waves. We found that hospitalized patients with confirmed infections in waves 2 and 3 were younger and more likely to be residing in small cities and rural areas than were patients in wave 1; they also had a higher risk for death, after adjustment for age and underlying medical conditions. Risk for death among hospitalized patients during waves 2 and 3 was lower in Jiangxi and Fujian Provinces than in eastern and southern provinces. The variation in risk for death among hospitalized case-patients in different areas across 3 epidemic waves might be associated with differences in case ascertainment, changes in clinical management, or virus genetic diversity.

Background: The disease burden of seasonal influenza is substantial in China, while the vaccination rate is extremely low, and most people have to pay 100% for vaccination. This study aims to examine willingness to pay (WTP) and recommended financing sources for influenza vaccination among children, chronic disease patients, and the elderly in China and determine feasible measures to expand vaccination coverage. Methods: From August to October 2019, 6668 children’s caregivers, 1735 chronic disease patients, and 3849 elderly people were recruited from 10 provinces in China. An on-site survey was conducted via a especially designed PAD system. Tobit regression was adopted to predict the influencing factors of WTP. Results: The average WTP was 127.5 yuan (USD18.0) for children, 96.5 yuan (USD13.7) for chronic disease patients, and 88.1 yuan (USD12.5) for the elderly. Most participants in the three groups thought government subsidies (94.8%, 95.8%, and 95.5%) or health insurance (94.3%, 95.3%, and 94.5%) should cover part of the cost, and nearly four-fifths (80.1%, 79.5%, and 76.8%) believed that individuals should also pay for part. Tobit regression showed that a higher perceived importance of vaccination, knowing about priority groups, and considering that individuals should co-pay were promoters of WTP, while considering price as a hindrance lowered WTP. Conclusions: The WTP for influenza vaccination among children, chronic disease patients, and the elderly in China is fairly high, suggesting that price is not the primary hindrance and there is room to expand immunization. Most participants expected the government and/or health insurance to pay part of the cost, and such supportive funding could act as a promotive policy “signal” to improve vaccine uptake. Influenza-related health education is also needed to expand vaccine coverage.

Seasonal influenza vaccination for healthcare workers (HCWs) is critical to the protection of HCWs and their patients. This study examined whether the separation of public health workers and general practitioners could affect the influenza vaccine uptake and recommendation behaviors among HCWs in China. A survey was conducted from August to October 2019, and HCWs from 10 provinces in China were recruited. A self-administered and anonymous questionnaire was used to assess HCWs’ demographic information, knowledge, and attitudes toward influenza vaccination, as well as vaccine uptake and recommendation behaviors. The primary outcome was HCWs’ vaccination and recommendation status of seasonal influenza vaccine. Multivariate logistic regression models were used to identify the influence factors of influenza vaccine uptake and recommendation among HCWs. Of the 1159 HCWs in this study, 25.3% were vaccinated against influenza in the previous season. “No need to get vaccinated” was the primary reason for both unvaccinated public health workers and general practitioners. Multivariate logistic regression showed that public health workers were more likely to get vaccinated against influenza (OR = 2.20, 95% CI 1.59–3.05) and recommend influenza vaccination to children (OR = 2.10, 95% CI 1.57–2.80) and the elderly (OR = 1.69, 95% CI 1.26–2.25) than general practitioners. Besides, the knowledge and perceived risk of influenza can give rise to HCWs’ vaccination and recommendation behaviors, and HCWs who got vaccinated in the past year were more likely to recommend it to children and the elderly in their work. The influenza vaccine coverage and recommendation among HCWs are still relatively low in China, especially for general practitioners. Further efforts are needed to improve the knowledge and attitudes toward influenza and influenza vaccination among HCWs, and coherent training on immunization for both public health workers and general practitioners might be effective in the face of separated public health and clinical services in China.

Objectives: To evaluate a policy-based intervention to increase seasonal-influenza-vaccination coverage in healthcare workers in Xining, a city in Western China. Methods: From October 2018 to March 2019, we implemented a free vaccination policy in healthcare workers in Xining. A face-to-face interview with the head of the infection control department and an online survey for medical staff in four tertiary medical facilities was conducted to understand both the implementation of the free policy and influenza vaccination coverage. Possible factors for influenza vaccination among healthcare workers (physician, nurses working on the front-line, HCWs) were investigated by multivariate-logistic regression. Results: Coverage in two hospitals that implemented the free vaccination policy was 30.5% and 25.9%, respectively, which was statistically different to hospitals that did not implement the free policy (7.2% and 8.7%, respectively) (χ2 = 332.56, p < 0.0001). Among vaccinated healthcare workers, 65.5% and 48.6% reported their main reasons for vaccination were a convenient vaccination service and awareness of the free vaccination policy. The reasons for not being vaccinated among the 3389 unvaccinated healthcare workers included: the inconvenient vaccination service (33.8%), believing vaccination was unnecessary (29.7%), concerns about adverse reactions to the vaccine (28.8%), and having to pay for the vaccine (25.6%). Conclusions: Implementing the free vaccination policy, combined with improving the accessibility of the vaccination service, increased seasonal-influenza vaccination-coverage in healthcare workers in Xining.

Influenza vaccination coverage was low among healthcare workers (HCWs) in China. In October 2018, the National Health Commission of China began to require all hospitals to provide free influenza vaccination for HCWs to increase vaccine uptake, and no study on vaccine coverage among HCWs at the national level after the announcement of new policy. This evaluation aims to investigate self-reported influenza vaccination coverage among HCWs and factors that may affect vaccine receipt during the 2018/2019 influenza season. We delivered an opt-in internet panel survey among registered HCWs of DXY forum (the biggest online forum for HCWs in China). The survey was self-administered using a standard questionnaire to collect information on demographics, occupational characteristics, policy implementation, influenza vaccination and influence factors. We conducted multivariate logistic regression analysis to assess factors associated with receipt of influenza vaccine. The response rate of this online survey was 3.6%. The seasonal influenza vaccine coverage reported among HCWs surveyed during the 2018/2019 season was 11.6% (472/4078). Only 19.0% (774/4078) of HCWs surveyed reported free policy in their workplace. Combing free policy and workplace requirement proved to be effective to improve influenza vaccination coverage in HCWs (PR = 6.90, 95% CI: 6.03−7.65). The influenza vaccination coverage among surveyed HCWs in China was low during the 2018/2019 season. To increase future vaccination uptake, we recommend a multi-faceted strategy that include free policy, workplace requirement and promotion, on-site vaccination, and monitoring.

BACKGROUND:Streptococcus pneumoniae (Sp) is a leading cause of bacterial pneumonia, meningitis, and sepsis and a major source of morbidity and mortality worldwide. Invasive pneumococcal disease (IPD) is defined as isolation of Sp from a normally sterile site, including blood or cerebrospinal fluid. The aim of this study is to describe outcomes as well as clinical and epidemiological characteristics of hospitalized IPD case patients in central China. METHODS:We conducted surveillance for IPD among children and adults from April 5, 2010 to September 30, 2012, in four major hospitals in Jingzhou City, Hubei Province. We collected demographic, clinical, and outcome data for all enrolled hospitalized patients with severe acute respiratory infection (SARI) or meningitis, and collected blood, urine, and cerebrospinal fluid (CSF) for laboratory testing for Sp infections. Collected data were entered into Epidata software and imported into SPSS for analysis. RESULTS:We enrolled 22,375 patients, including 22,202 (99%) with SARI and 173 (1%) with meningitis. One hundred and eighteen (118, 3%) with either SARI or meningitis were Sp positive, 32 (0.8%) from blood/CSF culture, and 87 (5%) from urine antigen testing. Of those 118 patients, 57% were aged ≥65 years and nearly 100% received antibiotics during hospitalization. None were previously vaccinated with 7-valent pneumococcal conjugate vaccine (PCV 7), 23-valent pneumococcal polysaccharide vaccine, or seasonal influenza vaccine. The main serotypes identified were 14, 12, 3, 1, 19F, 4, 5, 9V, 15 and 18C, corresponding to serotype coverage rates of 42%, 63%, and 77% for PCV7, PCV10, and PCV13, respectively. CONCLUSIONS:Further work is needed to expand access to pneumococcal vaccination in China, both among children and potentially among the elderly, and inappropriate use of antibiotics is a widespread and serious problem in China.

In response to several influenza A(H1N1)pdm09 infections that developed in passengers after they traveled on the same 2 flights from New York, New York, USA, to Hong Kong, China, to Fuzhou, China, we assessed transmission of influenza A(H1N1)pdm09 virus on these flights. We defined a case of infection as onset of fever and respiratory symptoms and detection of virus by PCR in a passenger or crew member of either flight. Illness developed only in passengers who traveled on the New York to Hong Kong flight. We compared exposures of 9 case-passengers with those of 32 asymptomatic control-passengers. None of the 9 case-passengers, compared with 47% (15/32) of control-passengers, wore a face mask for the entire flight (odds ratio 0, 95% CI 0–0.71). The source case-passenger was not identified. Wearing a face mask was a protective factor against influenza infection. We recommend a more comprehensive intervention study to accurately estimate this effect.

BACKGROUND:After the 2009 influenza A (H1N1) pandemic, we conducted hospital-based severe acute respiratory infection (SARI) surveillance in one central Chinese city to assess disease burden attributable to influenza among adults and adolescents. METHODS:We defined an adult SARI case as a hospitalized patient aged ≥ 15 years with temperature ≥38.0°C and at least one of the following: cough, sore throat, tachypnea, difficulty breathing, abnormal breath sounds on auscultation, sputum production, hemoptysis, chest pain, or chest radiograph consistent with pneumonia. For each enrolled SARI case-patient, we completed a standardized case report form, and collected a nasopharyngeal swab within 24 hours of admission. Specimens were tested for influenza viruses by real-time reverse transcription polymerase chain reaction (rRT-PCR). We analyzed data from adult SARI cases in four hospitals in Jingzhou, China from April 2010 to April 2012. RESULTS:Of 1,790 adult SARI patients enrolled, 40% were aged ≥ 65 years old. The median duration of hospitalization was 9 days. Nearly all were prescribed antibiotics during their hospitalization, less than 1% were prescribed oseltamivir, and 28% were prescribed corticosteroids. Only 0.1% reported receiving influenza vaccination in the past year. Of 1,704 samples tested, 16% were positive for influenza. Influenza activity in all age groups showed winter-spring and summer peaks. Influenza-positive patients had a longer duration from illness onset to hospitalization and a shorter duration from hospital admission to discharge or death compared to influenza negative SARI patients. CONCLUSIONS:There is substantial burden of influenza-associated SARI hospitalizations in Jingzhou, China, especially among older adults. More effective promotion of annual seasonal influenza vaccination and timely oseltamivir treatment among high risk groups may improve influenza prevention and control in China.

BACKGROUND:In early 2013, a novel avian-origin influenza A(H7N9) virus emerged in China, and has caused sporadic human infections. The incubation period is the delay from infection until onset of symptoms, and varies from person to person. Few previous studies have examined whether the duration of the incubation period correlates with subsequent disease severity. METHODS AND FINDINGS:We analyzed data of period of exposure on 395 human cases of laboratory-confirmed influenza A(H7N9) virus infection in China in a Bayesian framework using a Weibull distribution. We found a longer incubation period for the 173 fatal cases with a mean of 3.7 days (95% credibility interval, CrI: 3.4-4.1), compared to a mean of 3.3 days (95% CrI: 2.9-3.6) for the 222 non-fatal cases, and the difference in means was marginally significant at 0.47 days (95% CrI: -0.04, 0.99). There was a statistically significant correlation between a longer incubation period and an increased risk of death after adjustment for age, sex, geographical location and underlying medical conditions (adjusted odds ratio 1.70 per day increase in incubation period; 95% credibility interval 1.47-1.97). CONCLUSIONS:We found a significant association between a longer incubation period and a greater risk of death among human H7N9 cases. The underlying biological mechanisms leading to this association deserve further exploration.

Pandemic influenza A (H1N1) 2009 virus spread rapidly around the world in 2009. We used multiple data sources from surveillance systems and specific investigations to characterize the transmission patterns of this virus in China during May–November 2009 and analyze the effectiveness of border entry screening and holiday-related school closures on transmission. In China, age distribution and transmission dynamic characteristics were similar to those in Northern Hemisphere temperate countries. The epidemic was focused in children, with an effective reproduction number of ≈1.2–1.3. The 8 days of national holidays in October reduced the effective reproduction number by 37% (95% credible interval 28%–45%) and increased underreporting by ≈20%–30%. Border entry screening detected at most 37% of international travel–related cases, with most (89%) persons identified as having fever at time of entry. These findings suggest that border entry screening was unlikely to have delayed spread in China by >4 days.

Patterns of poultry exposure in rural and urban areas in China have not been systematically evaluated and compared. The objective of our study is to investigate patterns in human exposure to poultry in rural and urban China. We conducted a two-stage household-based clustered survey on population exposure to live/sick/dead poultry in Xiuning and Shenzhen. Half of the rural households (51%) in Xiuning raised poultry, mostly (78%) free-range. Around half of those households (40%) allowed poultry to stay in their living areas. One quarter of villagers reported having contact with sick or dead poultry. In Shenzhen, 37% urban residents visited live poultry markets. Among these, 40% purchased live poultry and 16% touched the poultry or cages during purchase. Our findings indicated that human exposure to poultry was different in rural and urban areas in China. This discrepancy could contribute to the observed differences in epidemiologic characteristics between urban and rural cases of influenza A(H7N9) and A(H5N1) virus infection.

The spread of infectious disease epidemics is mediated by human travel. Yet human mobility patterns vary substantially between countries and regions. Quantifying the frequency of travel and length of journeys in well-defined population is therefore critical for predicting the likely speed and pattern of spread of emerging infectious diseases, such as a new influenza pandemic. Here we present the results of a large population survey undertaken in 2007 in two areas of China: Shenzhen city in Guangdong province, and Huangshan city in Anhui province. In each area, 10,000 randomly selected individuals were interviewed, and data on regular and occasional journeys collected. Travel behaviour was examined as a function of age, sex, economic status and home location. Women and children were generally found to travel shorter distances than men. Travel patterns in the economically developed Shenzhen region are shown to resemble those in developed and economically advanced middle income countries with a significant fraction of the population commuting over distances in excess of 50 km. Conversely, in the less developed rural region of Anhui, travel was much more local, with very few journeys over 30 km. Travel patterns in both populations were well-fitted by a gravity model with a lognormal kernel function. The results provide the first quantitative information on human travel patterns in modern China, and suggest that a pandemic emerging in a less developed area of rural China might spread geographically sufficiently slowly for containment to be feasible, while spatial spread in the more economically developed areas might be expected to be much more rapid, making containment more difficult.

BACKGROUND: While human cases of highly pathogenic avian influenza A (H5N1) virus infection continue to increase globally, available clinical data on H5N1 cases are limited. We conducted a retrospective study of 26 confirmed human H5N1 cases identified through surveillance in China from October 2005 through April 2008. METHODOLOGY/PRINCIPAL FINDINGS: Data were collected from hospital medical records of H5N1 cases and analyzed. The median age was 29 years (range 6-62) and 58% were female. Many H5N1 cases reported fever (92%) and cough (58%) at illness onset, and had lower respiratory findings of tachypnea and dyspnea at admission. All cases progressed rapidly to bilateral pneumonia. Clinical complications included acute respiratory distress syndrome (ARDS, 81%), cardiac failure (50%), elevated aminotransaminases (43%), and renal dysfunction (17%). Fatal cases had a lower median nadir platelet count (64.5 x 10(9) cells/L vs 93.0 x 10(9) cells/L, p = 0.02), higher median peak lactic dehydrogenase (LDH) level (1982.5 U/L vs 1230.0 U/L, p = 0.001), higher percentage of ARDS (94% [n = 16] vs 56% [n = 5], p = 0.034) and more frequent cardiac failure (71% [n = 12] vs 11% [n = 1], p = 0.011) than nonfatal cases. A higher proportion of patients who received antiviral drugs survived compared to untreated (67% [8/12] vs 7% [1/14], p = 0.003). CONCLUSIONS/SIGNIFICANCE: The clinical course of Chinese H5N1 cases is characterized by fever and cough initially, with rapid progression to lower respiratory disease. Decreased platelet count, elevated LDH level, ARDS and cardiac failure were associated with fatal outcomes. Clinical management of H5N1 cases should be standardized in China to include early antiviral treatment for suspected H5N1 cases.