Background: Clinical and demographic predictors of intensive care unit (ICU) mortality risk in COVID-have been extensively characterised, yet the role of pre-admission environmental conditions in defining patient subgroups with distinct mortality risks remains unexplored. We used latent class analysis (LCA) to identify environmental subgroups among critically ill COVID-19 patients and examined how mortality risk and its clinical determinants vary across them. Methods: In this retrospective, multicentre cohort study, we analysed data from 1,166 adults admitted with PCR-confirmed COVID-19 to three Birmingham (UK) ICUs between March 2020 and February 2021. LCA was applied to pre-admission ambient temperature, relative humidity, and wind speed to derive discrete environmental profiles. Between-class mortality differences were quantified using relative risk (RR) estimation. Within each class, multivariable logistic regression examined covariate–mortality associations, adjusted for age, sex, ethnicity, deprivation, BMI, frailty, and Intensive Care National Audit Research Centre (ICNARC) Physiology Score. Findings were consistent in three sensitivity analyses addressing temporal confounding. Findings: Four environmentally distinct latent classes were identified. Relative to the reference class (moderate humidity; n=452), mortality was significantly elevated among patients admitted under warm, dry, and windy conditions (RR=1.62, 95% CI 1.14–2.29) and under mild temperatures with moderate-to-strong winds (RR=1.47, 95% CI 1.15–1.89). Associations between established clinical predictors and mortality varied significantly across classes. Interpretation: Pre-admission environmental conditions define distinct patient subgroups with systematically different mortality risks. Class-specific variation in the strength of established clinical predictors suggests that environmental context modifies how patient vulnerability translates into ICU mortality. These findings support further investigation of environmental profiling as a complementary dimension of ICU risk stratification, with potential applications in capacity planning during respiratory surges and pandemic preparedness.

BACKGROUND:The role of human rhinovirus (HRV) in adult lower respiratory tract infections (LRTIs) remains controversial due to limited direct evidence of alveolar tropism and age-specific clinical characterization. OBJECTIVES:To determine HRV's clinical impact, validate its capacity to infect lower respiratory tract cells, and identify predictors for HRV-associated pneumonia in adults. METHODS:In this retrospective study (January 2020-December 2023), all hospitalized adults screened for HRV via RT-PCR were enrolled for analysis. In bronchoalveolar lavage fluid (BALF)-HRV-RNA-positive patients with available transbronchial lung biopsy (TBLB) or transbronchial cryobiopsy (TBCB) specimens, immunofluorescence (IF) staining was used to assess infection of LRT cells. Multivariable logistic regression analyzed demographics, comorbidities, and symptoms. RESULTS:HRV was detected in 4.6% (437/9544) of patients, with bimodal seasonal peaks (February-April and September-November). Co-infection occurred in 49.0% (214/437), predominantly bacteria (34.1%) and viruses (25.7%). Among the 437 HRV-positive patients, 224 cases complicated with pneumonia, but only 34 (7.8%) met the diagnostic criteria for simple viral pneumonia. Multivariate analysis identified male (OR 2.69, 95% CI 1.04-6.99, P = .042), fever (OR 3.79, 95% CI 1.52-9.44, P = .004), and cough (OR 7.33, 95% CI 1.64-32.83, P = .009) as independent predictors of simple rhinovirus pneumonia. IF staining confirmed HRV VP3 protein in TBLB/TBCB specimens in 61.5% (8/13) of cases, resolving debates about HRV's LRT cells tropism. CONCLUSIONS:This study provides the first histological evidence of HRV's LRT cells infection in immunocompetent adults. Despite high co-infection rates, HRV independently drives pneumonia, particularly in males and those with fever or cough.

Respiratory diseases pose a significant threat to the health and lives of people. Although current vaccines targeting the respiratory pathogens can decrease disease severity, they mostly fail to effectively prevent infections and transmissions. Clearly identifying the clinical issues related to respiratory diseases, analyzing the important scientific questions surrounding airway mucosal immunity, and developing vaccines and therapeutic interventions based on the regulation of mucosal immune responses are key to addressing the issues of respiratory diseases. Here, we summarize the clinical pathological features of respiratory diseases and their relationship with pulmonary mucosal immunity. We also outline the immune response processes of respiratory mucosa represented by the pulmonary mucosa. On this basis, we reveiw the AI-based design strategies and mucosal delivery techniques for the respiratory diseases. We hope to summarize important clinical, fundamental, and technical issues in the research of respiratory mucosal immunity, thereby facilitating the exploration of new approaches for disease prevention and treatment.

Background The human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) represent a set of intersecting global health challenges due to the fact that they all involve the same transmission routes. Co-infection with HBV and/or HCV among people living with HIV (PLHIV) has been demonstrated to be associated with accelerated liver disease progression. Methods The present study examined the clinical implications of hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) in Jiangxi, China. A total of 810 HIV-positive individuals were enrolled in the study. Serological testing via ELISA was used to detect HBsAg and anti-HCV antibodies, while HBV DNA, HCV RNA, and HIV RNA levels were measured using quantitative real-time PCR. CD4+ T cell counts were subsequently analyzed using a technique known as flow cytometry. Results The results of the study indicated that the prevalence of HBsAg and anti-HCV antibodies in PLHIV was 12.8% and 8.3%, respectively. The prevalence of anti-HCV positivity was found to be significantly higher in the 31-50 age group compared to other age groups (P < 0.0001). Injection drug use (IDU) was identified as the primary route of HIV transmission among co-infected patients, accounting for 62.7% of HCV co-infections and 6.9% of HBV co-infections. Co-infected individuals exhibited elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and accelerated liver fibrosis progression in comparison to HIV-mono-infected patients evaluated using APRI and FIB-4. Antiretroviral therapy (ART) has been demonstrated to effectively reduce HIV viral load and increase CD4+ counts after a six-month treatment period. In addition, a positive correlation between HIV and HBV viral loads was observed in the ART group (r = 0.324, p = 0.008) rather than in ART-na & iuml;ve patients. Conclusion IDU is the main route for HCV infection in HIV/AIDS patients. Co-infection with HBV and/or HCV significantly promoted hepatic fibrosis, while the present ART regimens were effective for both HIV and HBV. Consequently, it is recommended to monitor the hepatic fibrosis level in PLHIV who are co-infected with HBV and (or) HCV.

Background: Immune checkpoint inhibitor-mediated pneumonitis (CIP) constitutes a major toxicity that limits the clinical application of cancer immunotherapy, whereas its underlying mechanisms remain incompletely understood. Current management relies on nonspecific immunosuppressants, lacking precision therapies. Although single-cell RNA sequencing (scRNA-seq) of bronchoalveolar lavage fluid (BALF) has implicated T cell activation and inflammatory myeloid responses in CIP pathogenesis, critical gaps persist regarding interstitial lung immunity and mechanisms governing monocyte/macrophage–T cell co-enrichment and crosstalk. We aimed to delineate the lung immune circuits that drive CIP and to identify targetable monocyte/macrophage–T cell pathways that could be leveraged for precision intervention. Methods: To elucidate CIP pathogenesis, we performed integrated scRNA-seq analysis of BALF from CIP + and CIP − patients with validation in a prospective cohort using flow cytometry, enzyme-linked immunosorbent assay, Western blotting, and quantitative polymerase chain reaction. Mechanistic studies were performed using an established tumor-bearing forkhead box P3–diphtheria toxin receptor–green fluorescent protein ( Foxp3-DTR-GFP ) mouse model of programmed death-1 inhibitor-induced CIP via micro-computed tomography, histopathology, scRNA-seq, flow cytometry, multiplex immunofluorescence, Western blotting, Transwell migration assays, and pharmacologic interventions. Results: In CIP + patient BALF and mouse lung tissues, CD8 + T cells expressing cytotoxic effectors and C-X-C chemokine receptor 3 (CXCR3) expanded concomitantly with distinct C-C chemokine receptor 2 (CCR2) + monocyte-derived macrophages (MoMΦ) exhibiting a highly inflammatory phenotype, while tissue-resident macrophages were markedly reduced. Mouse models revealed that expanded CCR2 + MoMΦ originating from circulation replenished the depleted niche of lung-resident interstitial macrophages. Mechanistically, integrated in silico prediction and experimental validation demonstrated that CCR2 + MoMΦ recruited CD8 + T cells via the C-X-C motif chemokine ligand 9/10 (CXCL9/10)–CXCR3 axis. Conversely, CD8 + T cells drove CCR2 + MoMΦ expansion and pro-inflammatory phenotype via the interferon-γ (IFN-γ) axis, suggesting the existence of a positive feedback loop between these cell types. Pharmacological targeting of CCR2/CCR5 or CXCR3 signaling attenuated pneumonitis, reduced pulmonary CCR2 + MoMΦ infiltration, diminished pathogenic T cell activation and cytotoxicity, and improved survival without compromising antitumor immunity. Conclusions: Our findings establish CCR2 + MoMΦ and the IFN-γ–CXCL9/10–CXCR3 axis as core drivers of CIP pathogenesis and validate their therapeutic targeting potential. This work provides a scientific foundation for developing CIP-specific prevention and treatment strategies.

ABSTRACT Coxsackievirus A6 (CVA6) has emerged as a predominant causative agent of hand, foot, and mouth disease worldwide. Efficient genomic surveillance is crucial for understanding its evolution and spread. Nanopore sequencing presents a promising platform for rapid and cost-effective viral genome sequencing directly from clinical samples. We developed a tiling amplicon-based nanopore sequencing protocol for CVA6. Eight clinical CVA6-positive samples, spanning a wide range of Ct values (15.54–25.28), were each serially diluted to three concentrations (undiluted, 10⁻¹, and 10⁻²), generating a total of 24 libraries. These libraries were sequenced using a PromethION flow cell and a MinION flow cell on PromethION and GridION platforms, respectively. Sensitivity was assessed across the dilution series, and accuracy was benchmarked against Illumina sequencing. The protocol demonstrated high sensitivity and speed, achieving >10× average sequencing depth within 5 mins using a PromethION flow cell. High genome coverage (≥96.5%) was consistently achieved across all samples, including serial dilutions, with minimal genetic divergence: only one to five single-nucleotide variants were observed between different dilution levels of the same specimen. Complete assembly was obtained from all test samples in the 10−2 dilutions (Ct: 21.73–32.7). Comparative genomic analysis revealed 99.81%–99.98% identity between Nanopore- and Illumina-derived consensus sequences, with sequences from the same sample clustering together phylogenetically. This study establishes a sensitive, accurate, and cost-effective nanopore sequencing workflow for CVA6 genomic surveillance directly from clinical specimens. The workflow delivers clear, data-informed implementation guidance, making it a practical tool for outbreak response and evolutionary tracking.IMPORTANCECoxsackievirus A6 (CVA6) has become a predominant cause of hand, foot, and mouth disease worldwide, necessitating rapid and accessible genomic surveillance. This study establishes a tiling amplicon-based nanopore sequencing protocol that delivers complete CVA6 genomes directly from clinical samples within hours. The workflow demonstrates high sensitivity across a wide range of Ct values, achieves >99.8% consensus accuracy compared to Illumina sequencing, and offers clear, data-driven guidelines for implementation. By enabling same-day, cost-effective genomic analysis, this approach equips public health laboratories with a practical tool for real-time outbreak response and tracking of viral evolution.

BACKGROUND:Nucleic acid testing (NAT) is essential for pathogen identification, disease diagnosis, and biomedical research. Traditional amplification-based methods, while widely used, often face challenges such as long processing times and susceptibility to false positives. Additionally, single-molecule detection approaches are limited by weak signal intensities and rapid photobleaching. To address these limitations, we present an amplification-free biosensing platform for the highly sensitive and specific single-molecule detection of Orientia tsutsugamushi DNA. RESULTS:This platform employs multi-fluorophore nucleic acid probes synthesized via click chemistry to significantly enhance signal intensity and photostability. Specifically, 5-Ethynyl-dUTP (5-EdUTP) was incorporated into PCR amplicons to enable conjugation with Cy5 fluorophores. Stochastic optical reconstruction microscopy (STORM) was employed as the readout method, enabling the localization and quantification of tens of thousands of single-molecule events and thereby achieving substantial signal amplification. The assay achieved a detection limit of 2.74 aM (equivalent to 27.4 ymol in a 10 μL system) with excellent specificity. Clinical validation with 11 samples demonstrated 100% sensitivity and specificity. SIGNIFICANCE:This approach offers a simple, rapid, and robust solution for single-molecule detection, providing an invaluable tool for detecting low-abundance biomarkers and holding great promise for early disease diagnosis.

BACKGROUND:The alveolar sac, which serves as the primary site for gas exchange, comprises alveolar type 1 (AT1) and alveolar type 2 (AT2) cells. These epithelial cells initiate immune responses upon encountering external stimuli. However, the influenza virus infection patterns and antiviral responses exhibited by different types of alveolar epithelial cells remain understudied. This study aimed to investigate the differential susceptibility and antiviral responses of AT1 and AT2 cells during influenza virus infection. METHODS:Immunofluorescence staining was performed to determine the spatial distribution of influenza A virus (IAV; H1N1). Primary murine epithelial in vitro culture models, including an AT2 sphere culture and an AT1 differentiation model, were established to elucidate the mechanisms underlying cellular susceptibility to IAV. Bulk RNA sequencing and quantitative polymerase chain reaction were performed to characterize the cellular responses to viral infection. RESULTS:Mouse AT2 cells exhibited greater susceptibility to H1N1 than did AT1 cells. The in vitro primary epithelial cell culture models mimicked the in vivo cellular phenotype. They further reproduced the in vitro finding of relatively high viral replication in AT2 cells. Mechanistically, no significant difference was observed between AT1 and AT2 cells in the expression of α-2,3 or α-2,6 sialic acid (viral receptors). However, RNA sequencing revealed that gene ontology terms such as the response to viral infection, negative regulation of the viral life cycle, and regulation of type I interferon (IFN) production were enriched in AT1 cells. This finding was validated using quantitative polymerase chain reaction. From 12 to 48 h after infection, the expression levels of types I and III IFNs, chemokines, and IFN-stimulated genes remained lower in AT2 cells than in AT1 cells. CONCLUSION:Our findings indicate the localization of IAV in alveoli and highlight the vulnerability of AT2 cells, which exhibit delayed immune responses, resulting in increased viral replication.

SUMMARYIn recent years, coxsackievirus A6 (CVA6) has become a predominant cause of hand, foot, and mouth disease (HFMD) worldwide, surpassing enterovirus A71 (EV-A71) and CVA16. The rise of CVA6 is of particular public health concern due to its association with atypical and severe clinical presentations, including extensive vesiculobullous eruptions and neurological complications. These diverse and often non-classical manifestations, which also occur in adults, complicate clinical diagnosis and highlight the need for enhanced molecular surveillance. Furthermore, the potential impact of enteroviral infection during pregnancy and on neonatal outcomes remains an important clinical consideration. While both structural and non-structural proteins of CVA6 are known to contribute to viral virulence, the underlying pathogenic mechanisms are not fully understood. Continuous evolution of CVA6 through genetic variation and frequent recombination has led to the emergence of distinct lineages and recombinants, posing substantial challenges to the development of effective antivirals and vaccines. To address these gaps, this review systematically examines the global epidemiology, pathogenic mechanisms, evolutionary dynamics, current diagnostic tools, and antiviral strategies for CVA6. By integrating these perspectives, this work aims to inform public health preparedness and guide future research toward mitigating outbreaks driven by emerging recombinants and novel enterovirus serotypes.

Enterococcus faecalis is a common gut commensal and an opportunistic pathogen causing hospital-acquired infections. Despite its clinical importance, comprehensive global genomic and epidemiological data remain limited. Here, we analyzed 5,895 E. faecalis genomes collected between 2000 and 2020 and identified ST179, a human-derived single-operon variant of the high-risk CC16 clonal complex, as an emerging epidemic clone in China. Spot-killing assays revealed that ST179 strongly inhibited other clinical E. faecalis sequence types. Biochemical purification and proteomic analyses identified BacL1 as a key effector associated with this species-specific antibacterial activity. Functional assays confirmed its inhibitory phenotype, providing ST179 with a lineage-specific, bacteriocin-mediated competitive advantage. The high prevalence of the Bac41 operon likely contributed to the epidemiological success and ecological fitness of ST179. These findings highlight the role of bacteriocin-mediated intraspecies competition in shaping E. faecalis population dynamics and suggest that ST179 might become an emerging high-risk lineage in China.IMPORTANCEEnterococcus faecalis is a common gut bacterium and an opportunistic pathogen. We identify ST179 as an emerging epidemic clone in China and show that it outcompetes other strains via the bacteriocin Bac41. This competitive advantage helps explain its rapid spread. Our findings highlight how bacterial competition shapes population dynamics and provide insights into the emergence of high-risk E. faecalis lineages, informing strategies for monitoring and infection control.

Aim:Metabolic diseases are increasingly prevalent worldwide and often coexist. However, the patterns of metabolic multimorbidity and their long-term associations with mortality remain poorly understood. This study aimed to characterize these patterns and evaluate their associations with all-cause and cause-specific mortality. Methods:This retrospective cohort study included 123,791 adults aged 25-74 years who underwent health examinations at a large medical center in northern China between 2015 and 2022. Five metabolic diseases were assessed: diabetes, hypertension, dyslipidemia, nonalcoholic fatty liver disease, and obesity. Metabolic multimorbidity was defined as the coexistence of two or more of these conditions. Cox proportional hazards models were used to estimate associations with all-cause, cardiovascular, and cancer mortality. Results:Among 123,791 participants (mean [SD] age, 41.3 [11.9] years; 50.8% male), 38,945 (31.5%) had metabolic multimorbidity. Prevalence was higher in men than in women (46.1% vs. 16.4%; P < 0.001). Age-related patterns differed by sex (P for interaction <0.001), with men showing a higher burden at younger ages and women showing a marked rise after midlife. During a median follow-up of 6.1 years (IQR, 4.2-7.6), 724 deaths (0.6%) occurred. Increasing numbers of coexisting diseases were associated with progressively higher risks of all-cause mortality (adjusted hazard ratios [aHRs], 1.38 [95% CI, 1.09-1.76] for one disease to 2.92 [1.82-4.68] for five diseases vs none; P for trend <0.001), cardiovascular mortality (aHRs, 1.78 [1.06-2.99] to 5.13 [2.25-11.7]; P for trend <0.001), and cancer mortality (aHRs, 1.36 [0.91-2.03] to 3.84 [1.90-7.78]; P for trend <0.001). Conclusion:Metabolic multimorbidity was highly prevalent and exhibited distinct age- and sex-related patterns, with a graded association with mortality risk. These findings may reflect shared pathophysiological mechanisms and support integrated, sex-specific strategies to mitigate the growing metabolic burden.

Objectives: This study aimed to elucidate the global epidemic trends and evolutionary characteristics of nine major non-polio enterovirus serotypes (CVA2, CVA4, CVA6, CVA10, CVA16, CVB3, CVB5, EV-A71, and EV-D68) through genomic data mining, focusing on their spatiotemporal distribution and evolutionary dynamics. Design: We employed a data mining framework integrating programming, phylogenetic analysis, Bayesian evolutionary modeling, and selection pressure assessment. Over 40,000 genomic sequences from GenBank were analyzed to reconstruct temporal phylogenies, estimate evolutionary rates, and characterize amino acid variability in the capsid protein VP1. Seasonal decomposition and spatial-temporal trend modeling were applied to evaluate epidemic patterns across the six WHO regions. Results: Key findings include [1]: Distinct biennial or triennial epidemic cycles for EV-D68 and clear seasonal peaks for HFMD-associated serotypes [2]; A preliminary observation termed the “60% Transcendence” phenomenon, where once cumulative VP1 nucleotide mutations reach approximately 60%, the cumulative non-synonymous amino acid mutations begin to exceed this threshold [3]; Evidence of episodic positive selection at critical VP1 codons, suggesting immune-driven evolution [4]; Divergent trends in relative genetic diversity, with EV-A71, CVA16, and CVA6 showing sustained expansion, while the diversity of CVB5 and EV-D68 declined sharply during the COVID-19 pandemic. Conclusions: This study provides valuable insights into the changing landscape of global enterovirus infections and underscores the critical role of genomic epidemiology in tracking their spread. Sustained research in this field is essential for developing effective strategies to prevent and control enterovirus-related diseases worldwide.

Coxsackievirus A6 (CVA6) has emerged as a predominant global pathogen of hand, foot and mouth disease, yet its evolutionary and molecular characteristics remain poorly understood. This study integrated 10 year molecular surveillance data from central China (2013-2024) with global CVA6 sequences to analyse high-entropy codons in the VP1 capsid protein and their co-evolution patterns. Phylogenetic and Bayesian evolutionary analyses indicated that CVA6 strains in China primarily clustered into sub-genotype D3, with an estimated global VP1 substitution rate of 3.62×10⁻³ substitutions/site/year. Shannon entropy analysis identified eight high-Shannon entropy codons in VP1 (sites 5, 29, 30, 97, 137, 174, 242, 283), with site 283 exhibiting the highest variability. A novel 283V variant (n=12) was uniquely detected in China after 2018. Direct-coupling analysis suggested co-evolution between residue pairs, most notably VP1-137 and VP1-242 (Direct information=0.44), where S137N may form new hydrogen bonds with 243 h, potentially contributing to structural changes that could influence immune evasion. Furthermore, S97N formed hydrogen bonds with D99, thereby altering the BC loop region. A spatiotemporal analysis showed that 283A replaced 283T on a global scale after 2017, while minor variants (e.g. 30D, 97I, 174A) exhibited localized circulation. These findings highlight the predominance of high-entropy codons in VP1 surface loops (BC, DE, EF and HI), suggesting ongoing adaptive selection pressure. Continuous genomic surveillance is imperative for tracking emerging variants (e.g. 283V, 97N) and for informing vaccine design against evolving CVA6 strains.

BACKGROUND: Severe influenza virus infection often triggers acute lung injury, and the efficacy of respiratory functional recovery critically depends on timely alveolar regeneration. However, the cellular dynamics and regulatory mechanisms underlying post-infectious alveolar repair remain incompletely understood. METHODS: Utilizing Sftpc-CreER; Rosa26-mTmG lineage-tracing model, we determine the main stem cell population responsible for alveolar regeneration following influenza-induced injury. Through integrated single-cell RNA sequencing (scRNA-seq), immunofluorescence, and electron microscopy approaches, we mapped cellular transcriptional landscapes and spatial interactions. Key macrophage-epithelial crosstalk was further investigated via in vitro co-culture systems and in vivo conditional depletion models using diphtheria toxin receptor-transgenic mice. Putative regulatory factors were predicted through ligand-receptor interaction analysis and functionally validated in ex vivo organoid models. RESULTS: In this study, we revealed that the severely damaged alveolar barrier after influenza virus infection was rebuilt by the proliferation and differentiation of residual type II alveolar epithelial (AT2) cells in an inflammatory niche. In particular, monocyte-derived macrophage (Mo-Macs) expand, displaying intimate spatial proximity with AT2 cells. In addition, the cellular transcriptional status determined by scRNA-seq revealed that Mo-Macs regulate epithelial cell proliferation. Mo-Macs promoted the formation of AT2 spheres in vitro. Moreover, Mo-Mac depletion resulted in delayed repair of the alveolar epithelial structure in vivo. In addition, the mechanism by which Mo-Macs regulate alveolar epithelial repair involves the secretion of oncostatin M (OSM), which stimulates p-STAT3 activation and promotes AT2 cell proliferation. CONCLUSIONS: Our findings revealed that residual AT2 cells act as stem cells in the alveolus and are regulated by Mo-Macs through OSM secretion. These findings increase our understanding of the role of inflammatory signals in regulating tissue repair after severe injury, which may provide a potential avenue for therapeutic intervention in recovered patients.

Scrub typhus is transmitted through vectors and is susceptible to meteorological factors, posing a significant threat to human life and health. Therefore, in this study, the nonlinear relationships between meteorological factors and scrub typhus (ST) and the lag effects of meteorological factors on ST were analyzed, and the explanatory power of these factors on the spatially stratified heterogeneity of ST was evaluated. Monthly data on ST cases and meteorological factors were collected in Jiangxi from 2014 to 2023. A distributed lag nonlinear model (DLNM) was used to analyze the lag effects and nonlinear relationships between meteorological factors and ST. Geodetector was conducted using 2023 spatial data to evaluate the explanatory power of meteorological factors and their interactions on the spatially stratified heterogeneity of ST. A total of 9129 cases of newly diagnosed ST were recorded. The DLNM demonstrated nonlinear relationships between meteorological factors and ST and lag effects of meteorological factors on ST. The influence of temperature, relative humidity, and wind speed on the ST initially increased, peaking at 25.50 °C, 84.80

BACKGROUND:Scrub typhus is an important zoonotic disease with rising incidence globally. Meteorological factors may influence its transmission dynamics. However, inconsistencies across studies and limited quantitative evidence highlight the need for further investigation. OBJECTIVE:To systematically evaluate the linear and nonlinear associations between various meteorological factors and scrub typhus incidence, explore lagged effects and potential sources of heterogeneity, and analyze inconsistencies in existing findings. METHOD:We searched PubMed, Scopus, Web of Science, and Embase for studies published up to February 2025. Relevant articles were identified based on predefined inclusion and exclusion criteria. We conducted linear meta-analyses to assess the effects of unit changes in meteorological factors and dose-response meta-analyses to evaluate cumulative lagged risks across different exposure levels. Subgroup and sensitivity analyses were conducted to explore sources of heterogeneity and assess result robustness. RESULTS:Seventeen studies were included, covering China, Korea, Laos, and India. Eleven studies contributed to linear meta-analyses, and six to dose-response analyses. Ambient temperature (RR 1.08, 95% CI 1.02-1.16), land surface temperature (RR 1.06, 95% CI 1.02-1.09), precipitation (RR 1.01, 95% CI 1.01-1.02), relative humidity (RR 1.07, 95% CI 1.04-1.11), and atmospheric pressure (RR 1.06, 95% CI 0.91-1.23) were positively associated with the risk of scrub typhus. Wind speed (RR 0.59, 95% CI 0.49-0.71) and sunshine duration (RR 0.92, 95% CI 0.77-1.10) exhibited negative associations. Dose-response meta-analysis revealed inverted U-shaped relationships for ambient temperature and relative humidity, and a unimodal pattern for precipitation, with risk increasing continuously at high levels. Significant lag effects were observed: precipitation had the most immediate effect (lag0: RR 1.05), while ambient temperature (lag1: RR 1.18) and relative humidity (lag2: RR 1.28) peaked with a 1- to 2-month delay. Geographic variation was identified as a major source of between-study heterogeneity. CONCLUSION:Although this study has certain limitations, including the small number of included studies, their concentration mainly in China, and the presence of substantial heterogeneity, the results provide evidence of linear and nonlinear associations between meteorological factors and scrub typhus incidence, and highlight the roles of geographical variation and lag effects. These findings offer quantitative evidence and scientific support for disease prevention and control in the context of climate change.

Clinical surveillance for respiratory pathogens has traditionally been challenging in low-resource settings, such as Western China. A low-cost wastewater monitoring network offers an alternative solution. To explore this, we first compared the sensitivity of a MeltArray-based qPCR assay, which detects 25 respiratory pathogens, with singleplex qPCR using both mock and real wastewater samples. We then employed this MeltArray assay to detect these respiratory pathogens in wastewater from a low-income region in Xi’an city from September 2023 to January 2024. Following this, qPCR and MLST were employed to quantify the dynamics of positive respiratory pathogens and confirm their genotypes. Results showed unusual surges in sewage influenza A virus (IAV) and adenovirus levels starting in October 2023, persisting until late December. Additionally, influenza B virus (IBV) outbreaks were identified beginning in late December. These findings matched the positivity rates reported by a sentinel hospital. For coronaviruses, HCoV-229E/OC43 were consistently detected in wastewater, while SARS-CoV-2 was occasionally found. The qPCR assays revealed continuous increases in sewage Mycoplasma pneumoniae and Hemophilus influenzae concentrations since September, both peaking in October. Genotyping confirmed the circulation of specific bacterial genotypes in the region. Therefore, to the best of our knowledge, this study is possibly the first to evaluate the efficacy of qPCR assays for wastewater monitoring of respiratory bacterial pathogens. Thus, these findings provide significant insights into the co-circulation of various respiratory pathogens during the autumn and winter of 2023, thereby suggesting that wastewater surveillance could be a powerful tool for the early warning of respiratory diseases.

This study examined the association between short-term exposure to air pollution and stroke mortality, and identified which types of stroke were most affected. Data on stroke mortality from 2014 to 2022 were extracted from the Population Death Register Information System of China Center for Disease Control and Prevention. Concentrations of air pollutants (PM2.5, PM10, SO2, NO2 and O-3) were obtained from the China Environmental Monitoring Center. Meteorological data (average daily temperature and humidity) were obtained from the China Meteorological Administration. A quasi-Poisson generalized additive model was used to assess the relationship between air pollutant and stroke mortality. Short-term air pollution exposure was positively associated with stroke mortality. Specifically, exposure to particulate matter (PM2.5, PM10) was more closely linked to ischemic stroke than to hemorrhagic stroke.Notably, for per 10 mu g/m(3) increase in PM2.5 (lag 02), PM10 (lag 03), SO2 (lag 04), and NO2 (lag 04), there was a corresponding increase in stroke mortality of 0.948% (95% CI: 0.022, 1.883), 0.697% (95% CI: 0.043, 1.354), 7.419% (95% CI: 3.227, 11.780) and 3.367% (95% CI: 1.398, 5.375), respectively. Stratified analyses indicated that the pollutants effects on stroke mortality varied by gender, age group and season.

Objective:Although AIP is a recognized cardiovascular risk marker, its association with pulmonary function and sex-specific differences remains unclear. This study investigated whether elevated AIP is independently associated with reduced lung function and examined potential sex-specific patterns. Methods:Data from 4,565 participants in the NHANES 2007-2012 dataset were analyzed using a cross-sectional design. AIP served as the exposure variable, with five lung function metrics (including FEV1, FVC, and FEV1/FVC ratio) as outcomes. Weighted multiple linear regression, threshold effect analysis, subgroup comparisons, and XGBoost modeling were performed to assess associations. Results:Multivariable regression showed a significant negative association between AIP and FEV1 (β = -121.3 mL/unit, p < 0.001) and FVC (β = -147.1 mL/unit, p < 0.001), with no significant link to FEV1/FVC ratio. Subgroup analysis revealed a U-shaped non-linear association in females, with inflection points at AIP values of 0.77 (FEV1) and 0.78 (FVC), beyond which declines in lung function plateaued. Males exhibited a consistent negative correlation across all AIP levels. Conclusion:Elevated AIP is independently associated with reduced lung function, particularly non-linear effects in females. These findings support AIP as a potential adjunct marker for pulmonary function assessment in clinical practice.

Antibiotic misuse has escalated globally, posing significant threats to public health. This rampant misuse not only fuels antibiotic resistance but also triggers the formation of anti-antibiotic antibodies, which may cause severe complications such as immune-mediated hemolytic anemia and compromise therapeutic efficacy. This review provides an in-depth analysis of this critical issue, evaluating both theoretical and clinical evidence regarding the emergence of these antibodies and elucidating their impact on clinical pharmacotherapy and severe complications, particularly in immune-mediated hemolytic anemia. Additionally, it underscores the growing challenge of antibiotic resistance and the pressing necessity for effective strategies to address this global health crisis.