Beijing Centers for Disease Control and Prevention

Background Temperature extremes are anticipated to become more frequent and more intense under the context of climate change. While current evidence on health effects of compound extreme temperature event is scarce. Methods This nationwide cross-sectional study collected daily data on weather and mortality for 161 Chinese districts/counties during 2007-2013. A quasi-Poisson generalized linear model was first applied to assess effects of daytime-only, nighttime-only and compound daytime-nighttime heat wave (and cold spell) on cause-specific mortality. Then a random-effect meta-analysis was used to produce pooled estimates at national level. Stratification analyses were performed by relative humidity, individual and regional characteristics. Results Here we show that mortality risks of compound daytime-nighttime temperature extremes are much higher than those occurring only in the daytime or nighttime. Humid weather further exaggerates the mortality risk during heat waves, while dry air enhances the risk during cold weather. People who are elderly, illiterate, and those with ischemic heart disease and respiratory disease are particularly vulnerable to extreme temperature. At the community-level, population size, urbanization rate, proportion of elderly and PM2.5 are positively associated with increased risks associated with heat waves. Temperature, humidity and normalized difference vegetation index are positively associated with the effects of cold weather, with an opposite trend for latitude and diurnal temperature range. Conclusions This nationwide study highlights the importance of incorporating compound daytime-nighttime extreme temperature events and humid conditions into early warning systems and urban design/planning.

Background Traumatic fractures occur frequently worldwide. However, research remains limited on the association between short-term exposure to temperature and traumatic fractures. This study aims to explore the impact of apparent temperature (AT) on emergency visits (EVs) due to traumatic fractures. Methods Based on EVs data for traumatic fractures and the contemporary meteorological data, a generalized Poisson regression model along with a distributed lag nonlinear model (DLNM) were undertaken to determine the impact of AT on traumatic fracture EVs. Subgroup analysis by gender and age and sensitivity analysis were also performed. Results A total of 25,094 EVs for traumatic fractures were included in the study. We observed a wide “J”-shaped relationship between AT and risk of traumatic fractures, with AT above 9.5 °C positively associated with EVs due to traumatic fractures. The heat effects became significant at cumulative lag 0–11 days, and the relative risk (RR) for moderate heat (95th percentile, 35.7 °C) and extreme heat (99.5th percentile, 38.8 °C) effect was 1.311 (95% CI: 1.132–1.518) and 1.418 (95% CI: 1.191–1.688) at cumulative lag 0–14 days, respectively. The cold effects were consistently non-significant on single or cumulative lag days across 0–14 days. The heat effects were higher among male and those aged 18–65 years old. The sensitivity analysis results remained robust. Conclusion Higher AT is associated with cumulative and delayed higher traumatic fracture EVs. The male and those aged 18–65 years are more susceptible to higher AT.

Introduction Due to the high cost and complexity, the oral glucose tolerance test is not adopted as the screening method for identifying diabetes patients, which leads to the misdiagnosis of patients with isolated post‐challenge hyperglycemia (IPH), that is., patients with normal fasting plasma glucose (<7.0 mmoL/L) and abnormal 2‐h postprandial blood glucose (≥11.1 mmoL/L). We aimed to develop a model to differentiate individuals with IPH from the normal population. Methods Data from 54301 eligible participants were obtained from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a longitudinal (REACTION) study in China. Data from 37740 participants were used to develop the diagnostic system. External validation was performed among 16561 participants. Three machine learning algorithms were used to create the predictive models, which were further evaluated by various classification algorithms to establish the best predictive model. Results Ten features were selected to develop an IPH diagnosis system (IPHDS) based on an artificial neural network. In external validation, the AUC of the IPHDS was 0.823 (95% CI 0.811–0.836), which was significantly higher than the AUC of the Taiwan model [0.799 (0.786–0.813)] and that of the Chinese Diabetes Risk Score model [0.648 (0.635–0.662)]. The IPHDS model had a sensitivity of 75.6% and a specificity of 74.6%. This model outperformed the Taiwan and CDRS models in subgroup analyses. An online site with instant predictions was deployed at https://app‐iphds‐e1fc405c8a69.herokuapp.com/ . Conclusions The proposed IPHDS could be a convenient and user‐friendly screening tool for diabetes during health examinations in a large general population.

Chronic hepatitis E mostly occurs in organ transplant recipients and can lead to rapid liver fibrosis and cirrhosis. Previous studies found that the development of chronic hepatitis E virus (HEV) infection is linked to the type of immunosuppressant used. Animal models are crucial for the study of pathogenesis of chronic hepatitis E. We previously established a stable chronic HEV infection rabbit model using cyclosporine A (CsA), a calcineurin inhibitor (CNI)-based immunosuppressant. However, the immunosuppression strategy and timing may be optimized, and how different types of immunosuppressants affect the establishment of chronic HEV infection in this model is still unknown. Here, we showed that chronic HEV infection can be established in 100% of rabbits when CsA treatment was started at HEV challenge or even 4 weeks after. Tacrolimus or prednisolone treatment alone also contributed to chronic HEV infection, resulting in 100% and 77.8% chronicity rates, respectively, while mycophenolate mofetil (MMF) only led to a 28.6% chronicity rate. Chronic HEV infection was accompanied with a persistent activation of innate immune response evidenced by transcriptome analysis. The suppressed adaptive immune response evidenced by low expression of genes related to cytotoxicity (like perforin and FasL ) and low anti-HEV seroconversion rates may play important roles in causing chronic HEV infection. By analyzing HEV antigen concentrations with different infection outcomes, we also found that HEV antigen levels could indicate chronic HEV infection development. This study optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits and highlighted the potential association between the development of chronic HEV infection and immunosuppressants. IMPORTANCE Organ transplant recipients are at high risk of chronic hepatitis E and generally receive a CNI-based immunosuppression regimen containing CNI (tacrolimus or CsA), MMF, and/or corticosteroids. Previously, we established stable chronic HEV infection in a rabbit model by using CsA before HEV challenge. In this study, we further optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits. Chronic HEV infection can also be established when CsA treatment was started at the same time or even 4 weeks after HEV challenge, clearly indicating the risk of progression to chronic infection under these circumstances and the necessity of HEV screening for both the recipient and the donor preoperatively. CsA, tacrolimus, or prednisolone instead of MMF significantly contributed to chronic HEV infection. HEV antigen in acute infection phase indicates the development of chronic infection. Our results have important implications for understanding the potential association between chronic HEV infection and immunosuppressants.

Influenza, a severe respiratory disease caused by the influenza virus, has long been a prominent threat to human health. An increasing number of studies have demonstrated that oral administration with probiotics may increase the immune response to lung infection via the gut-lung axis leading to the alleviation of the pulmonary disease. In this study, we evaluated the effects of oral administration of Pediococcus pentosaceus MIANGUAN2 (MIANGUAN2) on influenza infection in a mouse model. Our results showed that oral administration of MIANGUAN2 significantly improved weight loss, lung index, and lung pathology, and decreased lung viral load of influenza-infected mice. Additionally, MIANGUAN2-treated mice showed significantly lower levels of TNF-α, IL-1β, IFN-γ, and IL-12p70 and higher production of IL-4 in the lung. In accordance with this, the transcriptome analysis of the lung indicated that MIANGUAN2-treated mice had reduced expression of inflammation markers, such as TNF, apoptosis, and the NF-Kappa B pathway. Furthermore, the administration of MIANGUAN2 restored the SCFAs profiles through regulating the gut microbiota. SCFA-producing bacteria, such as p_Firmicutes, f_Lachnospiraceae, and f_Ruminococcaceae, were enriched in the MIANGUAN2-treated group compared with PBS-treated group. Consistently, the concentrations of SCFAs in the MIANGUAN2 group were significantly higher than those in the PBS-treated group. In addition, the concentrations of SCFAs were positively correlated with SCFA-producing bacteria, such as Ruminococcus, while being negatively correlated with the virial titers and proinflammatory cytokines. In conclusion, this animal study suggests that Pediococcus pentosaceus MIANGUAN2 may alleviate the influenza infection by altering the gut microbiota composition and increasing the levels of gut microbiota-derived SCFAs.

What is already known about this topic? Foodborne diseases present a significant public health concern, particularly in China, where they represent a significant food safety challenge. Currently, there is a need for a thorough and systematic analysis of the extended epidemiological patterns of foodborne diseases in Beijing Municipality. What is added by this report? Monitoring results show that Norovirus and diarrheagenic Escherichia coli (DEC) are the most commonly identified foodborne diarrheal pathogens. Individuals aged 19–30 are at a higher risk of foodborne diarrhea in Beijing, with Salmonella infection being associated with fever symptoms. What are the implications for public health practice? This study analyzes 11 years of consecutive monitoring data to enhance understanding of the epidemiological and clinical features of foodborne diarrhea in Beijing. It aims to identify high-risk populations, assist in clinical pathogen identification and treatment, and support the development of tailored preventive strategies.

What is already known about this topic? Foodborne diseases, representing significant food safety and public health challenges globally, are not well-documented in terms of incidence, particularly for cases characterized by acute gastroenteritis (AGI) in China. What is added by this report? This study developed a pyramid model to estimate the incidence of five pathogens, stratified by gender and age. The estimated incidences per 100,000 people with 95% uncertainty intervals (UI) are as follows: Norovirus, 3,188.28 (95% UI: 2,518.03, 7,296.96); Salmonella spp., 1,295.59 (95% UI: 1,002.62, 1,573.11); diarrheagenic E. coli (DEC), 782.62 (95% UI: 651.19, 932.05); Vibrio parahaemolyticus, 404.06 (95% UI: 342.19, 468.93); and Shigella spp., 26.73 (95% UI: 21.05, 33.46). What are the implications for public health practice? This study elucidates the incidence rates across various gender and age groups, thereby identifying priority populations for targeted preventive interventions aimed at reducing disease burden. These insights are crucial for the development of public health policies and management of food safety risks.

Introduction Human prion disease (PrD), a group of fatal and transmissible neurodegenerative diseases, consists of Creutzfeldt–Jakob disease (CJD), kuru, fatal familial insomnia (FFI), Gerstmann-Sträussler-Scheinker disease (GSS), and variably protease-sensitive prionopathy (VPSPr). The emergence of bovine spongiform encephalopathy (BSE) in cattle and variant CJD (vCJD) has greatly threatened public health, both in humans and animals. Since the 1990's, dozens of countries and territories have conducted PrD surveillance programs. Methods In this study, the case numbers and alternative trends of different types of PrD globally and in various countries or territories from 1993 to 2020 were collected and analyzed based on the data from the websites of the international and national PrD surveillance programs, as well as from relevant publications. Results The total numbers of the reported PrD and sporadic CJD (sCJD) cases in 34 countries with accessible annual case numbers were 27,872 and 24,623, respectively. The top seven countries in PrD cases were the USA (n = 5,156), France (n = 3,276), Germany (n = 3,212), Italy (n = 2,995), China (n = 2,662), the UK (n = 2,521), Spain (n = 1,657), and Canada (n = 1,311). The annual PrD case numbers and mortalities, either globally or in the countries, showed an increased trend in the past 27 years. Genetic PrD cases accounted for 10.83% of all reported PrD cases; however, the trend varied largely among the different countries and territories. There have been 485 iatrogenic CJD (iCJD) cases and 232 vCJD cases reported worldwide. Discussion The majority of the countries with PrD surveillance programs were high- and upper-middle-income countries. However, most low- and lower-middle-income countries in the world did not conduct PrD surveillance or even report PrD cases, indicating that the number of human PrD cases worldwide is markedly undervalued. Active international PrD surveillance for both humans and animals is still vital to eliminate the threat of prion disease from a public health perspective.

Background This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1. Methods Humanized fragments, consisting of the endothelial cell‐specific K18 promoter, human ST6GAL1‐encoding gene, and luciferase gene, were microinjected into the fertilized eggs of mice. The manipulated embryos were transferred into the oviducts of pseudopregnant female mice. The offspring were identified using PCR. Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation, and in vivo analysis was performed for screening. Expression of the humanized gene was tested by performing immunohistochemical (IHC) analysis. Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed. Results Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1. Seven mice were identified as carrying copies of the humanized gene, and the in vivo analysis indicated that hST6GAL1 gene expression in positive mice mirrored influenza virus infection characteristics. The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice. Moreover, the hematologic and biochemical parameters of the positive mice were within the normal range. Conclusion A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

Background Flea bites could trigger a series of complex molecular responses in the host. However, our understanding of the responses at the molecular level is still relatively limited. This study quantifies the changes in gene expression in mice after flea bites by RNA sequencing (RNA-seq) from their spleens, revealing the potential biological effects of host response to flea bites. Methods RNA-seq was used for transcriptome analysis to screen for differentially expressed genes (DEGs) between the control mice group and the flea bite mice group. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on DEGs. Protein–protein interaction (PPI) network analysis on DEGs related to immune processes was performed. Finally, we randomly selected several genes from the screened DEGs to validate the results from the transcriptome data by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Results A total of 521 DEGs were identified, including 277 upregulated and 244 downregulated. There were 258 GO terms significantly enriched by upregulated DEGs and 419 GO terms significantly enriched by downregulated DEGs. Among the upregulated DEGs, 22 GO terms were associated with immune cells (e.g., B cells and T cells) and immune regulatory processes, while among the downregulated DEGs, 58 GO terms were associated with immune cells and immune regulatory processes. Through PPI analysis, we found that CD40 molecules with significantly downregulated expression levels after flea bites may play an important role in host immune regulation. Through KEGG pathway enrichment analysis, a total of 26 significantly enriched KEGG pathways were identified. The RT-qPCR analysis results indicated that the transcriptome sequencing results were reliable. Conclusions Through in-depth analysis of transcriptome changes in mice caused by flea bites, we revealed that flea bites could stimulate a series of biological and immunological responses in mice. These findings not only provided a deeper understanding of the impact of flea bites on the host but also provided a basis for further research on the interaction between ectoparasites and the host. We believe that digging deeper into the significance of these transcriptome changes will help reveal more about the adaptive response of the host to ectoparasites. Graphical Abstract

Anthrax is an acute infectious zoonotic disease caused by Bacillus anthracis, a bacterium that is considered a potential biological warfare agent. Bacillus bacteriophages shape the composition and evolution of bacterial communities in nature and therefore have important roles in the ecosystem community. B. anthracis phages are not only used in etiological diagnostics but also have promising prospects in clinical therapeutics or for disinfection in anthrax outbreaks. In this study, two temperate B. anthracis phages, vB_BanS_A16R1 (A16R1) and vB_BanS_A16R4 (A16R4), were isolated and showed siphovirus-like morphological characteristics. Genome sequencing showed that the genomes of phages A16R1 and A16R4 are 36,569 bp and 40,059 bp in length, respectively. A16R1 belongs to the genus Wbetavirus, while A16R4 belongs to the genus Hubeivirus and is the first phage of that genus found to lyse B. anthracis. Because these two phages can comparatively specifically lyse B. anthracis, they could be used as alternative diagnostic tools for identification of B. anthracis infections.

Background Hemorrhagic fever with renal syndrome (HFRS) continues to pose a significant public health threat to the population in China. Previous epidemiological evidence indicates that HFRS is climate sensitive and influenced by meteorological factors. However, past studies either focused on too-narrow geographical regions or investigated time periods that were too early. There is an urgent need for a comprehensive analysis to interpret the epidemiological patterns of meteorological factors affecting the incidence of HFRS across diverse climate zones. Objective In this study, we aimed to describe the overall epidemic characteristics of HFRS and explore the linkage between monthly HFRS cases and meteorological factors at different climate levels in China. Methods The reported HFRS cases and meteorological data were collected from 151 cities in China during the period from 2015 to 2021. We conducted a 3-stage analysis, adopting a distributed lag nonlinear model and a generalized additive model to estimate the interactions and marginal effects of meteorological factors on HFRS. Results This study included a total of 63,180 cases of HFRS; the epidemic trends showed seasonal fluctuations, with patterns varying across different climate zones. Temperature had the greatest impact on the incidence of HFRS, with the maximum hysteresis effects being at 1 month (–19 ºC; relative risk [RR] 1.64, 95% CI 1.24-2.15) in the midtemperate zone, 0 months (28 ºC; RR 3.15, 95% CI 2.13-4.65) in the warm-temperate zone, and 0 months (4 ºC; RR 1.72, 95% CI 1.31-2.25) in the subtropical zone. Interactions were discovered between the average temperature, relative humidity, and precipitation in different temperature zones. Moreover, the influence of precipitation and relative humidity on the incidence of HFRS had different characteristics under different temperature layers. The hysteresis effect of meteorological factors did not end after an epidemic season, but gradually weakened in the following 1 or 2 seasons. Conclusions Weather variability, especially low temperature, plays an important role in epidemics of HFRS in China. A long hysteresis effect indicates the necessity of continuous intervention following an HFRS epidemic. This finding can help public health departments guide the prevention and control of HFRS and develop strategies to cope with the impacts of climate change in specific regions.

Accurate diagnostic techniques and effective therapeutic methods are required to treat H. pylori. The application of chicken single-chain variable fragment (scFv) antibodies may diagnose and treat H. pylori. This study used the phage display technique to construct a chicken-derived immune scFv antibody library against H. pylori. Total RNA was extracted from the spleens of five immunized chickens and reverse transcribed into cDNA. A fragment of scFv was produced by overlap extension PCR and cloned into a pHEN2 phagemid vector. After the package with the M13KO7 helper phage, the recombinant HpaA protein was used as a target antigen to validate the screening ability of our antibody library by bio-panning. The dilution counting results showed that the size of the primary antibody library was estimated to be 1 × 109 cfu/mL. PCR analysis of 47 clones from the library revealed that about 100% of the clones were positive with scFv fragments, and there were no identical sequences, indicating the good diversity of the antibody library. After three rounds of bio-panning, high-affinity antibodies against recombinant HpaA protein were successfully obtained. The selected antibody specifically recognized HpaA protein in nine different H. pylori strains, confirming the screening ability of our library. The chicken immune scFv antibody library against H. pylori was successfully constructed, and the antibody library’s screening ability was validated by selecting specific scFv antibodies against recombinant HpaA and clinical strains. It provided a simple and rapid method to obtain antibodies against H. pylori for diagnosis or treatment.

Debates surrounding the efficacy of influenza vaccination for survival benefits persist, and there is a lack of data regarding its duration of protection. A self‐controlled case series (SCCS) and a 1:4 matched case‐control study were conducted using the National Health Interview Survey (NHIS) and public‐use mortality data from 2005 to 2018 in the United States. The SCCS study identified participants who received influenza vaccination within 12 months before the survey and subsequently died within 1 year of postvaccination. The matched case‐control study paired participants who died during the influenza season at the time of survey with four survivors. Among 1167 participants in the SCCS study, there was a 46% reduction in all‐cause mortality and a 43% reduction in cardiovascular mortality within 29–196 days of postvaccination. The greatest protection was observed during days 29–56 (all‐cause mortality: RI: 0.19; 95% CI: 0.12–0.29; cardiovascular mortality: RI: 0.28; 95% CI: 0.14–0.56). Among 626 cases and 2504 controls included in the matched case‐control study, influenza vaccination was associated with a reduction in all‐cause mortality (OR: 0.74, 95% CI: 0.60–0.92) and cardiovascular mortality (OR: 0.64, 95% CI: 0.44–0.93) during the influenza season. This study highlights the importance of influenza vaccination in reducing the risks of all‐cause and cardiovascular mortality, with effects lasting for approximately 6 months.

Keratinocyte proliferation and differentiation in epidermis are well-controlled and essential for reacting to stimuli such as ultraviolet light. Imbalance between proliferation and differentiation is a characteristic feature of major human skin diseases such as psoriasis and squamous cell carcinoma. However, the effect of keratinocyte metabolism on proliferation and differentiation remains largely elusive. We show here that the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) promotes differentiation while inhibits proliferation of keratinocyte and suppresses psoriasis development. FBP1 is identified among the most upregulated genes induced by UVB using transcriptome sequencing and is elevated especially in upper epidermis. Fbp1 heterozygous mice exhibit aberrant epidermis phenotypes with local hyperplasia and dedifferentiation. Loss of FBP1 promotes proliferation and inhibits differentiation of keratinocytes in vitro. Mechanistically, FBP1 loss facilitates glycolysis-mediated acetyl-CoA production, which increases histone H3 acetylation at lysine 9, resulting in enhanced transcription of proliferation genes. We further find that the expression of FBP1 is dramatically reduced in human psoriatic lesions and in skin of mouse imiquimod psoriasis model. Fbp1 deficiency in mice facilitates psoriasis-like skin lesions development through glycolysis and acetyl-CoA production. Collectively, our findings reveal a previously unrecognized role of FBP1 in epidermal homeostasis and provide evidence for FBP1 as a metabolic psoriasis suppressor.

Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. From 2018 to 2023, a surge in severe neonatal cases and fatalities linked to a novel variant of genotype D5 was documented in China, France, and Italy. However, the prevention and control of E11 variants have been hampered by limited background data on the virus circulation and genetic variance. Therefore, the present study investigated the circulating dynamics of E11 and the genetic variation and molecular evolution of genotype D5 through the collection of strains from the national acute flaccid paralysis (AFP) and hand, foot, and mouth disease (HFMD) surveillance system in China during 2000-2022 and genetic sequences published in the GenBank database. The results of this study revealed a prevalent dynamic of E11 circulation, with D5 being the predominant genotype worldwide. Further phylogenetic analysis of genotype D5 indicated that it could be subdivided into three important geographic clusters (D5-CHN1: 2014-2019, D5-CHN2: 2016-2022, and D5-EUR: 2022-2023). Additionally, variant-specific (144) amino acid mutation sites and positive-selection pressure sites (132, 262) were identified in the VP1 region. Cluster-specific recombination patterns were also identified, with CVB5, E6, and CVB4 as the major recombinant viruses. These findings provide a preliminary landscape of E11 circulation worldwide and basic scientific data for further study of the pathogenicity of E11 variants.

The emerging evidence of human infections with emerging viruses suggests their potential public health importance. A novel taxon of viruses named Statoviruses (for st ool‐ a ssociated To mbus‐like viruses) was recently identified in the gastrointestinal tracts of multiple mammals. Here we report the discovery of re spiratory St atovirus‐like viruses (provisionally named Restviruses) from the respiratory tracts of five patients experiencing acute respiratory disease with Human coronavirus OC43 infection through the retrospective analysis of meta‐transcriptomic data. Restviruses shared 53.1%–98.8% identities of genomic sequences with each other and 39.9%–44.3% identities with Statoviruses. The phylogenetic analysis revealed that Restviruses together with a Stato‐like virus from nasal‐throat swabs of Vietnamese patients with acute respiratory disease, formed a well‐supported clade distinct from the taxon of Statoviruses. However, the consistent genome characteristics of Restviruses and Statoviruses suggested that they might share similar evolutionary trajectories. These findings warrant further studies to elucidate the etiological and epidemiological significance of the emerging Restviruses.