House dust mites (HDMs), particularly Dermatophagoides farinae, are commonly found in household dust and play a key role in allergic diseases such as asthma and allergic rhinitis. Beyond clinical management, allergen removal strategies are crucial for improving quality of life. Hence, this study investigated the effects of ozone exposure on D. farinae, focusing on changes in protein expression, surface bacterial composition, mortality, and mobility. Mites were exposed to ozone concentrations of 0.05, 0.5, and 1 ppm for 24, 48, and 72 h in a controlled chamber, with non-exposed mites serving as controls. Western blotting using anti-Der f 1 and anti-Blo t 5 antibodies assessed changes in allergen profiles, while 16 S rRNA sequencing characterised changes in surface bacterial communities. Mortality was evaluated using 100 mites per group under varying exposure durations. To assess behavioural responses, a three-chamber mobility assay was conducted, where mites were placed in a central compartment flanked by no-ozone and low-ozone chambers, and their distribution was recorded after 72 h. Ozone exposure resulted in a concentration- and time-dependent reduction of Der f 1 protein intensity, suggesting allergen degradation. Surface bacterial profiling revealed distinct compositional shifts following ozone exposure. Mortality increased proportionally with ozone concentration and duration. In the mobility assay, mites predominantly remained in the no-ozone chamber, indicating avoidance of ozone. Collectively, these findings demonstrate that ozone exposure affects D. farinae at molecular, microbial, and behavioural levels, highlighting ozone's potential role in modulating mite allergenicity and ecology.
To evaluate the accuracy of maxillary canine and anchorage tooth movement in first premolar extraction cases at final canine retraction, using In-house clear aligners (IHCA), by comparing the palatal power arm (PA) to control (C). A single-center randomized controlled trial with a split-mouth design was used. University. Eighteen adults requiring extraction of maxillary first premolars were recruited and received multi-stage IHCA treatment. Outcomes include 3 linear (mesio-distal, bucco-lingual, extrusion-intrusion) and 3 angular (tipping, rotation, torque) measurements. The primary outcome was canine distalization. Sequence generation: Patients were assigned to the PA and control sides using sequence-based randomization (Research-Randomizer website). Allocation concealment and blinding were not feasible. Pretreatment and canine final aligner virtual and actual digital models were superimposed using the 3D GOM-Inspect-Suite software to assess 6 types of tooth movement. Equivalence testing with Holm-Bonferroni correction was used to compare mean differences and 90% confidence intervals (CI) between PA and control sides for maxillary canines and anchorage teeth. For canine linear movements, the mean differences ranged from -0.19 to 0.09 mm, with corresponding 90% confidence intervals entirely within the predefined equivalence margins of ± 0.5 mm, indicating practical equivalence. In contrast, canine rotation was not equivalent, with a mean difference of 5.22° and a 90% CI of (1.48, 8.95), which exceeded the predefined equivalence bounds of ± 1.5°. Similarly, canine distal crown tipping failed to demonstrate equivalence, with a mean difference of 1.67° and a 90% CI of (- 0.44, 3.78). For anchorage movements, most linear outcomes met the equivalence criteria, except for premolar mesialization and molar buccalization, whereas angular outcomes generally did not, as their confidence intervals were not fully contained within the equivalence region. These findings suggest loss of anchorage on both sides, characterized by mesial crown tipping and relative intrusion, indicating that the PA may not significantly preserve anchorage. Linear movements were equivalent between the PA and control, whereas canine angular movements did not demonstrate equivalence. Potential benefit of PA in angulation and rotation control should be interpreted with caution. These findings may have limited generalizability, especially to commercial aligners. Trial Registration Current Controlled Trials ISRCTN 14020146 of the International Standard Randomized Controlled Trial.
To analyze the allergenicity spectrum characteristics of house dust mite (HDM) components (Der p 1, Der p 2, Der p 10, Der p 23) in HDM-allergic children from the Beijing area, and explore the associations between sensitization to these components and allergic rhinitis (AR) with comorbid allergic asthma (AA) or atopic dermatitis (AD). Using a cross-sectional study design, 221 children (140 males and 81 females) aged 4-16 years with positive serum HDM-specific immunoglobulin E (sIgE) who attended Beijing Civil Aviation General Hospital from March 2024 to May 2025 were included. AR, AA and AD were diagnosed and grouped according to established guidelines. Serum total IgE and component-specific sIgE levels(Der p 1, Der p 2, Der p 10, Der p 23) were measured using chemiluminescence. The results showed that Der p 2 and Der p 1 were the predominant sensitizing components, with sensitization rates of 62.0% (137/221) and 58.8% (130/221) respectively, followed by Der p 23 (17.2%, 38/221), and Der p 10 (9.0%, 20/221), among the 221 children. The median concentration of Der p 2-sIgE (1.41 kUA/L) was significantly higher than that of Der p 1 (0.27 kUA/L). Co-sensitization to Der p 1 and Der p 2 was the most common pattern (29.0%, 64/221). The sensitization rates to Der p 1 were significantly higher in the AR with AA group compared to the AR without AA group (χ2=5.157,P<0.05). After adjusting for age, sex, total IgE, and the number of sensitized inhalant allergens in multivariate logistic regression and using a more stringent sIgE positivity threshold (≥0.70 kUA/L), Der p 1 sensitization remained independently associated with an increased risk of asthma co-morbidity (aOR=2.22, 95%CI: 1.137-4.316, P<0.05). In the subgroup analysis of children with asthma co-morbidity, Der p 1-sIgE concentration showed a significant positive correlation with asthma severity (aOR=1.16, 95%CI: 1.020-1.310, P<0.05). No significant associations were found between component sensitizations and AD comorbidity(χ2=1.534, 0.299, 1.243, 0.316, P>0.05). In conclusion,among the children with dust mite allergy in Beijing area studied Der p 1 sensitization demonstrates a robust and independent association with asthma comorbidity and correlates with asthma severity, whereas the highly immunogenic component Der p 2 does not have an independent association with asthma. These provides a reference for component-resolved diagnosis, individualized risk assessment, and precision immunotherapy for pediatric HDM-allergic diseases in the Beijing area. 本研究分析北京地区屋尘螨过敏儿童组分致敏谱特征，并探讨主要组分（Der p 1、Der p 2、Der p 10、Der p 23）致敏与过敏性鼻炎（AR）共患过敏性哮喘（AA）和特应性皮炎（AD）的相关性。本研究采用横断面研究设计，纳入2024年3月至2025年5月于民航总医院就诊的4~16岁、血清屋尘螨特异性免疫球蛋白E抗体（sIgE）阳性的儿童221例（男性140例，女性81例）。依据指南标准诊断AR、AA和AD并进行分组。采用磁微粒化学发光法检测血清总IgE（tIgE）及组分sIgE水平（Der p 1、Der p 2、Der p 10、Der p 23）。结果显示，221例患儿中，Der p 2与Der p 1为主要致敏组分，致敏率分别为62.0%（137/221）与58.8%（130/221），Der p 23为17.2%（38/221），Der p 10最低（9.0%，20/221）。Der p 2-sIgE浓度中位数（1.41 kUA/L）显著高于Der p 1（0.27 kUA/L）。Der p 1与Der p 2共致敏最常见（29.0%，64/221）。AR伴AA组Der p 1致敏率高于AR不伴AA组（χ2=5.157，P<0.05）。调整年龄、性别、tIgE及吸入物致敏种类，sIgE采用≥0.70 kUA/L阳性阈值后，多因素logistic回归模型分析结果显示，Der p 1致敏仍与哮喘共病风险独立相关（aOR=2.22，95%CI：1.137~4.316，P<0.05）。在哮喘共病亚组分析中Der p 1-sIgE浓度与哮喘严重程度呈正向关联（aOR=1.16，95%CI：1.020~1.310，P<0.05）。各组分致敏与AD共病无显著关联（χ2=1.534、0.299、1.243、0.316，P>0.05）。综上，本研究的屋尘螨过敏儿童中，Der p 1致敏与哮喘共病存在稳健的显著独立关联。而高免疫原性组分（Der p 2）与哮喘无独立关联。这为北京地区儿童尘螨过敏性疾病的组分解析诊断、个体化风险评估及精准免疫治疗提供了参考依据。.
ObjectivesOur aim was to evaluate clinical and renal histopathological variables associated with the diagnosis of Systemic Lupus Erythematosus (SLE) in a South American cohort with Full-House (FH) glomerulonephritis (GN) in order to distinguish it from other causes of FHGN.MethodsObservational retrospective study. Kidney biopsies performed in our hospital between 2000 and 2019 were reviewed, identifying those with a FH pattern. Clinical, analytical, and histopathological data were collected. Patients were classified as SLE with Lupus - FHGN (if they met ACR 1997 and/or SLICC 2012 and/or ACR-EULAR 2019 SLE criteria) and as non-Lupus FH GN (idiopathic or secondary). Descriptive statistics, univariate and multivariate logistic regression analysis were performed to identify factors associated with Lupus- FHGN, and Kaplan-Meier survival curves were used to compare renal survival between both groups.Results181 patients with FHGN were included, 124 women (68.5%), with a mean age of 41.1 years (SD 16.0) and a median post-biopsy follow-up time of 2.9 years (IQR 0.4-6.8 years). 116 patients (64.1%) met SLE criteria (103 with extrarenal manifestations and 13 with renal-limited lupus), 52 patients presented identifiable secondary causes of FHGN and 13 remained idiopathic FHGN. Renal biopsies in Lupus - FHGN presented more frequently 3 or 4 crosses of IgG, C3 and C1q deposits (p < 0.001) and had less moderate/severe involvement of the tubulointerstitial compartment (p < 0.001), when compared with non-Lupus FHGN. In the multivariate analysis, the factors that remained associated with Lupus - FHGN were: female sex, younger age, positive ANA, anti-DNA, and 3 or 4 crosses of C1q deposits. Lupus - FHGN showed a protective effect for the development of End-Stage Renal Disease (ESRD) in the univariate analysis (HR 0.34, 95% CI 0.13-0.89) but this association was not significant in the multivariate analysis.ConclusionsIn this South American cohort, 35.9% of FHGN were not associated with SLE diagnosis. Female sex, younger age, positive ANA or anti-DNA antibodies and marked C1q deposits at renal biopsy were associated with SLE diagnosis.
Despite known confounds of social isolation on rodent behavior, many investigators rely on singly housing mice to assess alcohol preference in preclinical models of alcohol use disorder (AUD). This protocol describes a social alcohol drinking task that allows for high-throughput, automated assessment of alcohol drinking behaviors in mice without the confounding impacts of stress induced by social isolation. The IntelliCage testing system enables investigators to simultaneously assess operant alcohol drinking behavior in up to 16 same-sex mice, each uniquely identified with a subcutaneously implanted radiofrequency identification (RFID) transponder. Access to sipper bottles is software-controlled and can be adjusted individually for each mouse. In this chronic, intermittent alcohol drinking paradigm, mice voluntarily engage in operant nosepokes to access sipper bottles containing 20% alcohol for six consecutive weeks. Alcohol bottles are only accessible every other day for 24 h at a time and can be optionally adulterated with quinine to assess punishment-insensitive drinking. Visits to each operant corner, nosepokes, and lick data are automatically recorded for each mouse. Detailed experimental methods and the open-source code to analyze the recorded data will allow investigators to assess alcohol drinking behaviors relevant to AUD in an increasingly efficient and ethologically relevant manner.
Accurate kidney ultrasound segmentation is fundamental for clinical measurement and computer-aided diagnosis. However, domain shifts across devices and centers-manifested as differences in grayscale intensity, contrast, and speckle texture statistics-can substantially degrade model generalization, while acquiring new pixel-level annotations is costly. To address this, we propose a statistical spectral-similarity-guided ultrasound-to-ultrasound translation method to improve kidney segmentation performance without target-domain annotations. Motivated by frequency-domain analysis of renal ultrasound data, we observe that mid-to-low frequency components, which encode global organ structure, exhibit high consistency across domains, whereas mid-to-high frequency components, dominated by device-dependent speckle and texture statistics, vary substantially. Based on dataset-level frequency statistics, our method automatically identifies spectrally similar frequency bands shared by the source and target domains and derives structural guidance from them. This guidance is injected as a soft condition throughout a diffusion-based image generation process, enabling translation to target-device appearance while preserving anatomical structure. The translated images, paired with source-domain labels, are then used to train a segmentation network without requiring any target-domain annotations. Experiments on two public renal ultrasound datasets (OKUS and UNK) and an in-house multi-center dataset demonstrate superior structural preservation in image translation and consistently improved downstream segmentation performance, with particularly large reductions in boundary error. In the challenging OKUS to UNK adaptation scenario, our method boosts the mean Dice score by up to 20.52% (from 56.05% to 76.57%) and drastically reduces the 95% Hausdorff Distance (HD95) boundary error by 71.96 mm compared to the direct transfer baseline. Furthermore, consistent performance gains are achieved across the in-house multi-center dataset. These results indicate that the proposed spectral-similarity-based guidance effectively handles ultrasound domain shifts, substantially improving robustness and generalization for kidney segmentation under zero-shot and cross-center settings.
Bladder cancer is one of the most common malignancies worldwide, and only a subset of patients derives durable benefit from immune checkpoint blockade. An immune-cold tumor microenvironment, characterized by limited immune infiltration and impaired antitumor activity, is a major barrier to immunotherapy efficacy. However, the tumor-intrinsic factors that contribute to immune exclusion in bladder cancer remain incompletely understood. This study aimed to investigate the role of VSIG2 in shaping the immune microenvironment and immunotherapy response in bladder cancer. Integrative analyses were performed using bulk transcriptomic data, a Xiangya validation cohort, public single-cell RNA-seq datasets, and a Xiangya single-cell immunotherapy cohort. Immune-related transcriptional programs, immune cell infiltration, and cancer immunity cycle activity were evaluated by differential expression, enrichment, and immune deconvolution analyses. The cellular source and biological features of VSIG2 were further characterized at single-cell resolution. Clinical relevance was assessed by immunohistochemistry and response-associated analyses in immunotherapy-treated samples. Functional validation was performed in an MB49 syngeneic mouse model with VSIG2 knockdown combined with anti-PD-1 treatment. VSIG2 was associated with an immune-cold phenotype in bladder cancer across multiple independent cohorts. In bulk transcriptomic analyses, VSIG2-high tumors exhibited reduced activity across several steps of the cancer immunity cycle, decreased infiltration of T cells, cytotoxic lymphocytes, and NK cells, and suppression of inflammatory, chemokine-related, and antigen-presentation programs. These findings were independently validated in the in-house cohort. Single-cell analyses showed that VSIG2 was predominantly enriched in malignant epithelial cells and marked tumor cell states characterized by weaker antigen-presentation, interferon-response, and immune interaction programs. In the in-house single-cell immunotherapy cohort, lower VSIG2 expression was associated with immunotherapy response and a more inflamed immune contexture. In vivo, VSIG2 silencing inhibited tumor growth, increased CD8-positive T-cell infiltration, and enhanced the antitumor efficacy of PD-1 blockade. VSIG2 is a tumor-associated molecule linked to immune exclusion and reduced responsiveness to PD-1 blockade in bladder cancer. Elevated VSIG2 expression marks malignant cell states with impaired immune engagement, whereas targeting VSIG2 enhances antitumor immunity and improves immunotherapy efficacy in vivo. These findings identify VSIG2 as a potential biomarker and therapeutic target for overcoming immunotherapy resistance in bladder cancer.
Allergic asthma is characterized by chronic airway inflammation and heightened type 2 immune responses. Although inhaled corticosteroids are the mainstay of therapy, a subset of patients exhibits suboptimal responses, underscoring the need for new therapeutic targets. In this study, we investigated the role of novel B cell-related interleukin-40 (IL-40) in allergic asthma using patient samples and a house dust mite (HDM)-induced mouse model. Through transcriptomic and immunological profiling, our findings revealed that IL-40 expression was significantly upregulated in both patients with allergic asthma and murine model. Elevated IL-40 levels exacerbated airway hyperresponsiveness (AHR), promoted inflammatory cell infiltration, and increased the production of type 2 cytokines, indicating a key role in amplifying allergic airway inflammation. Importantly, treatment with a neutralizing antibody against IL-40 or genetic deletion of IL-40 significantly alleviated airway inflammation, suggesting its therapeutic potential. Mechanistically, these pro-inflammatory effects of IL-40 were closely associated with alterations in macrophage polarization and B cell development. Macrophages exhibited the highest induction of IL-40 secretion following allergen exposure and responded most strongly to IL-40 stimulation. This response involved the activation of the JAK/STAT1 and p38-MAPK signaling pathways, driving their polarization toward a pro-inflammatory phenotype while inhibiting the differentiation of a specific Arg1+ macrophage subset. Although T cells did not display a direct response to IL-40 stimulation, IL-40 was found to be essential for normal B cell development. IL-40-/- mice showed a marked reduction in pre-B cells in the bone marrow and impaired B cell maturation in the spleen, characterized by decreased follicular B cell populations. Genes involved in B cell receptor synthesis and complement activation were notably downregulated in IL-40-/- mice. These findings position IL-40 as a key regulator of allergic asthma pathogenesis and suggest its potential as a novel biomarker and therapeutic target for airway inflammation.
High-altitude hypobaric conditions may cause prolonged wound hypoxia and impaired healing, yet standardized models remain scarce. In this study, we developed a wound delayed healing model and preliminarily validated it by simulating high-altitude hypoxia using a controlled hypobaric system. Rats were housed at simulated altitudes of 3000 m (air pressure: 70.1 kPa, partial oxygen pressure: 14.7 kPa) to 8000 m (air pressure: 35.6 kPa, partial oxygen pressure: 7.5 kPa) to determine safety thresholds, with oxidative stress and skin hypoxia assessed. Results showed increased mortality risk at simulated 6000 m altitude, with tolerance observed below 5000 m. Elevated altitudes were associated with worsening oxidative stress and increased skin hypoxia; exhibited altitude-dependent delays in wound healing, reduced perfusion, suppressed collagen remodeling, and exacerbated inflammatory responses. Despite upregulation of vascular regenerative factors, microvascular density decreased. Overall, this study developed and preliminarily validated a rat model suitable for investigating mechanisms and interventions in high-altitude hypoxia-induced chronic wounds.
Background: Asthma involves chronic inflammation linked to metabolic reprogramming, but how metabolites reshape epigenetics through posttranslational modifications remains unclear. Methods: We used house dust mite (HDM)-induced asthmatic mice with multiomics analyses (metabolomics, posttranslational modification-proteomics, and chromatin immunoprecipitation sequencing) and validated findings through gene editing and adeno-associated virus interventions. Results: Asthmatic airways showed lactate-driven glutaminolysis, causing lactate/succinate accumulation. Phosphoenolpyruvate carboxykinase 2 (PCK2) succinylation at K100 enhanced stability by antagonizing ubiquitination, creating a lactate-generating feedback loop. Accumulated lactate triggered polyglutamine-binding protein 1 (PQBP1) lactylation at K223, enabling protein arginine methyltransferase 5 (PRMT5)/WD repeat domain 77 complex inhibition. This erased H4R3me2s repressive marks from proinflammatory gene promoters, particularly mitogen-activated protein kinase pathway genes, causing transcriptional derepression. Airway epithelium-specific Pqbp1 knockout reduced inflammation, goblet cell hyperplasia, and T helper 2 responses. Pck2-short hairpin RNA or oxamate treatment ameliorated asthmatic pathology. Conclusion: We identified a PCK2-lactate-PQBP1-PRMT5 axis linking metabolic reprogramming to epigenetic dysregulation in asthma. PCK2-K100 succinylation drives lactate accumulation, inducing PQBP1-K223 lactylation that inhibits PRMT5 and activates inflammatory genes, representing a therapeutic target for asthma.
Dairy calves are typically reared in environments that differ greatly from naturalistic conditions: separated from their dam after birth, housed without peer contact, and unable to graze or have outdoor access. An improved understanding of the effect of the farming environment on calves' affective states may help refine management practices to improve dairy calf welfare. In this narrative review, we examine how characteristics of dairy calf rearing systems relate to both short- and long-term affective states. Affective states are commonly inferred from behavioral proxy measures (e.g., changes in time budgets, play, etc.) or conditioned responses to affective-state paradigms. We categorized environmental elements through physical, social, and temporal components and discuss the current knowledge on their effects on indicators of affective states. Consistent evidence supports that physical features such as adequate milk allowance, different sources of solid food (e.g., concentrate and forage), soft and dry lying surfaces; and a social environment allowing full contact with conspecifics appear important for promoting positive affective states and reducing negative ones in dairy calves. Although the temporal characteristics of environmental features remain comparatively underexplored, available evidence suggests factors such as timing, predictability, and control can modulate how physical and social components are experienced. Overall, knowledge regarding longer-lasting mood states in dairy calves remains limited. Addressing these gaps through future research could help refine rearing practices that support not only the reduction of negative states, but also the promotion of positive welfare in dairy calves.
Porphyromonas gingivalis and Prevotella intermedia are key oral pathogens implicated in periodontal disease and have been associated with rheumatoid arthritis and specific categories of juvenile idiopathic arthritis. Whether oral dysbiosis involving Porphyromonas gingivalis or Prevotella intermedia contributes to axial spondyloarthritis pathogenesis remains unclear. We evaluated Porphyromonas gingivalis- and Prevotella intermedia-specific IgG titres across early axial spondyloarthritis phenotypes within the DESIR cohort and assessed the potential influence of smoking status. Serum samples from 554 participants in the DESIR cohort were analyzed. Anti-Porphyromonas gingivalis and anti-Prevotella intermedia IgG titres were measured using a validated in-house enzyme-linked immunosorbent assay. Patients were classified into axial spondyloarthritis, axial spondyloarthritis with psoriasis, axial spondyloarthritis with inflammatory bowel disease, undifferentiated axial spondyloarthritis, or chronic low back pain controls. Antibody titres were compared using non-parametric tests. In addition, multivariable logistic and linear regression analyses were performed adjusting for age, sex, BMI and smoking status. Anti-Porphyromonas gingivalis and anti-Prevotella intermedia IgG titres did not differ significantly across axial spondyloarthritis phenotypes or between axial spondyloarthritis subgroups and chronic low back pain controls (Porphyromonas gingivalis: p = 0.622; Prevotella intermedia: p = 0.491). These findings remained unchanged after multivariable adjustment for age, sex, BMI, and smoking status (all p > 0.1). Smoking status did not influence serological patterns in any group. Distributional analyses confirmed strong overlap in antibody titres across all phenotypes, with no subgroup showing a distinct P. gingivalis or P. intermedia serological signature. In this large early axial spondyloarthritis cohort, antibody responses to Porphyromonas gingivalis and Prevotella intermedia did not differ across phenotypes and showed no detectable serological association with axSpA. These findings did not support a major role of Porphyromonas gingivalis - or Prevotella intermedia-related systemic humoral responses in early axial spondyloarthritis, although they did not exclude a broader role of mucosal dysbiosis in disease pathogenesis.
Dust mites (DM) are important allergens for allergic rhinitis (AR) and allergic asthma (AA). This study aims to analyze the component characteristics of dust mite-sensitized patients in Shenzhen and to explore the association between specific IgE (sIgE) levels of particular components and AR as well as AR combined with AA. A retrospective cross-sectional cohort study was conducted to analyze patients who visited the Department of Allergy, Nanshan District People's Hospital of Shenzhen from December 2023 to December 2024 and were diagnosed with allergic rhinitis (AR) with or without concurrent allergic asthma (AA). Serum samples were collected from these patients during their outpatient visits.DM recombinant protein component reagents and the DiXun DX-Blot 45II high-throughput fully automatic immunoblotting instrument were used to detect sIgE levels of dust mite (Dermatophagoides farinae, Der f) component Der f 1, Der f 2 and house dust mite (Dermatophagoides pteronyssinus, Der p) component Der p 1, Der p 2, Der p 5, Der p 7, Der p 10, Der p 21, Der p 23 by protein chip method. The aim was to examine the relationship between sIgE levels and AR and AA, as well as to identify the sensitizing components and multiple sensitizing components in AR patients. The Mann-Whitney U test was used to compare the differences in the sIgE levels of each component between the AR group and the AR complicated with AA group.The results showed that A total of 124 patients with AR induced by DM were included, including 66 (53.2%) with simple allergic rhinitis (AR) and 58 (46.8%) with AR combined with AA. The sensitization rates for DM components, from highest to lowest, were:Der p 2 (84.7%), Der f 2(84.7%), Der f 1(81.5%), Der p 1(74.2%), Der p 23(58.9%), Der p 21(33.1%), Der p 7 (24.2%), Der p 5 (22.6%), Der p 10(6.5%). The proportions of grade≥4 for Der p 2 (χ²=4.617, P=0.032) and Der f 2 (χ²=6.260, P=0.012). In the AR combined with AA group, the proportion of cases with grade 4 or higher was significantly higher than in the AR group (P<0.05), the difference was statistically significant. However, there were no significant differences among other components(P>0.05). The sIgE levels of Der p 1, Der f 1, Der p 2, and Der f 2 were significantly higher in the AR combined with AA group than in the AR group (P<0.05), with a small to moderate effect size.Among these, the difference in Der p 2, Der f 2 was the most significant (P<0.001). The higher sIgE levels in the AR combined with AA group may suggest a stronger correlation between comorbidities and immune responses.The sensitization of house dust mite components was characterized by multi-component sensitization (positive for more than 2 house dust mite component proteins), among which AR group was 79.1%, AR combined with AA group was 81.1%, and the multi-component sensitization of AR combined with AA group was slightly higher than that of AR group, without significant difference.(P>0.05) In conclusion, The main sensitization components of DM are component 1 (Der p 1 and Der f 1), component 2 (Der p 2 and Der f 2) and Der p 23 in Shenzhen region. The sIgE levels of dust mite components were higher in the AR with AA group than in the AR alone group. Component 2 (Der p 2 and Der f 2) is more likely to induce allergic reactionswith higher sIgE levels in patients of the AR combined with AA group. In this study, no significant difference was found in the sensitization rate to multiple components between the allergic rhinitis (AR) group and the AR combined with allergic asthma (AA) group. 尘螨（DM）是变应性鼻炎（AR）和变应性哮喘（AA）的重要致敏原。本研究旨在分析深圳市尘螨致敏患者的组分特征，并探讨特定组分特异性IgE（sIgE）水平与AR及AR伴AA之间的关联。本研究采用横断面研究方法，分析2023年12月至2024年12月就诊于深圳市南山区人民医院过敏反应科且诊断为AR伴或不伴AA的患者，门诊收集患者的血清样本，采用蛋白芯片法检测粉尘螨（Der f）组分Der f 1、Der f 2以及屋尘螨（Der p）组分Der p 1、Der p 2、Der p 5、Der p 7、Der p 10、Der p 21、Der p 23的sIgE，观察sIgE数值与AR和AR伴AA的关系特征，观察AR和AR伴AA患者的致敏组分特征及多组分致敏的特征。利用Mann-Whitney U比较AR和AR伴AA组间各组分sIgE水平差异。结果显示，纳入124例DM诱发的AR患者，其中单纯性变应性鼻炎（AR）的患者66例（53.2%），AR伴AA的患者58例（46.8%）。DM组分致敏率由高到低排列依次为：Der p 2（84.7%）、Der f 2（84.7%）、Der f 1（81.5%）、Der p 1（74.2%）、Der p 23（58.9%）、Der p 21（33.1%）、Der p 7（24.2%）、Der p 5（22.6%）、Der p 10（6.5%）。Der p 2（χ²=4.617，P=0.032）和Der f 2（χ²=6.260，P=0.012）在AR伴AA组中≥4级的比例显著高于AR组（P<0.05），差异具有统计学意义，而其他组分无显著差异（P>0.05）。Der p 1、Der f 1、Der p 2、Der f 2的sIgE水平在AR伴AA组中显著高于AR组（P<0.05），效应量为小到中等。其中Der p 2、Der f 2的差异最显著（P<0.001），AR伴AA组sIgE更高可能提示合并症与免疫应答之间的关联性更强。屋尘螨组分致敏表现为多组分致敏（≥2种屋尘螨组分蛋白阳性）的特点，其中AR组为79.1%，AR伴AA组为81.1%，AR伴AA组多组分致敏略高于AR组，差异无统计学意义（P>0.05）。综上，深圳地区DM的主要致敏组分为组分1（Der p 1和Der f 1）、组分2（Der p 2和Der f 2）和Der p 23。AR伴AA组的患者组分sIgE数值高于AR组的患者。组分2（Der p 2和Der f 2）在AR伴AA组的患者中可能更易引发更高sIgE等级的过敏反应。本研究未发现多组分致敏比例在AR与AR伴AA组间存在显著差异。.
Objective: To investigate the changes in the positive rate of specific immunoglobulin E (sIgE) for inhalant and ingestive allergens in children at a certain children's hospital in Wuhan City from 2019 to 2024, and to analyze the characteristics of allergen sensitization in different age groups, genders, and seasons, as well as the trend of allergen changes over different years. Methods: A cross-sectional retrospective study was conducted. Clinical data of 64 116 children aged 0-16 years who visited Wuhan Children's Hospital and underwent sIgE testing for 20 common inhalant and ingestive allergens from January 2019 to December 2024 were collected. The patients were divided into the infant group (25 955 cases, 0-3 years old), the preschool group (22 167 cases, 4-6 years old), the school-age group (15 061 cases, 7-12 years old), and the adolescent group (767 cases, 13-16 years old). Non-parametric rank sum test and χ2 were used for analysis and comparison. Results: A total of 64 116 children with suspected allergic diseases from 2019 to 2024 were included. Among them, the overall positive rate of allergen sIgE was 33.2% (21 258/64 116 cases). Comparison of the positive rate of allergens between different years showed statistically significant differences (χ2=987.392, P<0.05), and a significant upward trend was observed after 2020-2022, with 35.8% (5 416/15 122 cases) and 39.2% (4 872/12 433 cases) in 2023 and 2024, respectively. The top 4 inhalant allergens with the highest positive rate of sIgE in suspected allergic disease children from 2019 to 2024 were Dermatophagoides farinae, house dust, Alternaria alternata, and cat epithelium. Milk, eggs, wheat flour, and soybeans were the main top 4 ingestive allergens. The positive rate of allergens in male children was higher than that in female children for house dust mites, house dust, Alternaria alternata, peanuts, soybeans, milk, crabs, shrimp, eggs, codfish, and wheat flour, with statistically significant differences (P<0.05). There were statistically significant differences in the positive rate of inhalant and ingestive allergens among different age groups (except for common ragweed, mugwort, cockroach, crabs, beef, and mutton), and the positive rate of multiple allergens was higher in the preschool group, such as 33.5% (7 437/22 167 cases) for eggs, 33.1% (6 903/22 167 cases) for Dermatophagoides farinae, and 26.5% (5 876/22 167 cases) for milk. The detection rate of multiple sensitizations increased year by year (The χ2 trend test value is 2 796.539 7, P<0.05), and the proportion of quadruple or more (i.e., detection of 4 or more positive allergens) sensitization reached 12.1% (1 504/12 433 cases) in 2024. The comparison of the positive rate of inhalant and ingestive allergens between seasons showed statistically significant differences (P<0.05). Conclusion: There are distinct gender, age and seasonal distribution characteristics of allergens in children in Wuhan area. 目的： 探讨2019—2024年武汉市某儿童医院儿童吸入性与食入性过敏原特异性免疫球蛋白E（sIgE）的阳性率变化，分析不同年龄、性别、季节过敏原致敏特点以及不同年份间过敏原的变化趋势。 方法： 采用横断面研究方法，收集2019年1月至2024年12月在武汉儿童医院就诊并接受20种常见吸入与食入性过敏原sIgE检测的0~16岁疑似过敏性疾病患儿临床资料，共纳入64 116例。分为婴幼儿组25 955例（0~3岁）、学龄前期组22 167例（4~6岁）、学龄期组15 061例（7~12岁）和青少年组767例（13~16岁）。采用χ2检验进行分析比较。 结果： 共纳入2019—2024年门诊和住院共64 116例疑似过敏性疾病患儿，64 116例患儿中，过敏原sIgE总体阳性率为33.2%（21 258/64 116例）。不同年份间过敏原阳性率比较，差异具有统计学意义（χ2=987.392，P<0.05），且在2020—2022年后呈明显上升趋势，2023年及2024年分别为35.8%（5 416/15 122例）和39.2%（4 872/12 433例）。2019—2024年疑似过敏性疾病患儿sIgE阳性率最高的前4位吸入性过敏原为粉尘螨、屋尘、交链孢霉和猫上皮，牛奶、鸡蛋、小麦面粉以及大豆为主要的前4位食入性过敏原。屋尘螨、屋尘、交链孢霉、花生、大豆、牛奶、螃蟹、虾、鸡蛋、鳕鱼、小麦面粉在男性患儿中检测过敏原阳性率高于女性，差异有统计学意义（P<0.05）；各年龄组间吸入性和食入性过敏原（除了普通豚草、艾蒿、蟑螂、螃蟹、牛肉、羊肉）sIgE阳性率差异均有统计学意义（P<0.05），学龄前期组多种过敏原阳性率较高，如鸡蛋阳性率为33.5%（7 437/22 167例）、粉尘螨阳性率为33.1%（6 903/22 167例）、牛奶阳性率为26.5%（5 876/22 167例）。多重致敏检出率逐年上升（χ2趋势值为2 796.539 7，P<0.05），2024年四重及以上（即检出4种及以上过敏原阳性）致敏占比达12.1%（1 504/12 433例）。季节间吸入性与食入性过敏原阳性率比较，差异均有统计学意义（P<0.05）。 结论： 武汉地区儿童过敏原存在明显的性别、年龄及季节分布特征。.
A 4-year-old spayed female mixed breed dog presented for chronic upper airway noises and dysphagia. The dog presented for inspiratory stridor and expiratory stertor. Serum creatine kinase activity was 3,296 IU/L, and cholesterol and triglyceride levels were elevated at 353 mg/dL and 201 mg/dL, respectively. In-house thyroxine levels were below the reference range, prompting the submission of a comprehensive thyroid profile to an outside reference laboratory. Head and cervical CT with contrast showed perivertebral/perilaryngeal muscle thickening and contrast enhancement. Electrodiagnostics of the pelvic limbs and head showed diffuse spontaneous activity with normal motor nerve conduction velocity. Muscle biopsies revealed an inflammatory myopathy in both masticatory muscles and pelvic limb muscles. The serum 2M antibody titer was positive. Comprehensive infectious PCR and serology testing were negative. The constellation of findings is compatible with an overlap syndrome of masticatory myositis and immune-mediated polymyositis. A comprehensive thyroid panel consisting of total thyroxine, total triiodothyronine, free thyroxine by dialysis, T4 and T3 autoantibodies, thyroid-stimulating hormone, and thyroglobulin autoantibodies later returned supported results for lymphocytic thyroiditis. Treatment with immunosuppressive doses of prednisone was effective in reducing, but not eliminating, the respiratory noises and dysphagia, with improved quality of life 763 days after initial presentation. This is a clinical description of an overlap syndrome of masticatory myositis and polymyositis, further complicated by lymphocytic thyroiditis. This case report highlights the importance of differentiating euthyroid sick syndrome and lymphocytic thyroiditis in dogs with chronic immune-mediated illness.
Dietary polyphenols, including proanthocyanidins, have emerged as potential modulators of metabolic health. Evidence supports benefits on glucose and hepatic metabolism in diet-induced obesity. However, reported effects vary widely across polyphenol sources and experimental design, and the key physiological mediators of benefit in established obesity remain incompletely defined. Moreover, ambient temperature, a key determinant of metabolic phenotype that may influence therapeutic responses, is rarely considered. Here we aim to determine the metabolic effects and mechanisms of action of a proanthocyanidin-rich cranberry extract (PRCE) in established diet-induced obesity under cold (10°C) and thermoneutral (30°C) housing conditions. Male mice with established obesity were supplemented with PRCE or vehicle while housed at 10°C or 30°C. Metabolic phenotyping included body composition, glucose homeostasis, intestinal carbohydrate digestion and glucose absorption, circadian profiling of peripheral and central clocks, and gut microbiota analysis. PRCE supplementation significantly improved glycemia and glucose tolerance independently of temperature, without altering body weight, adiposity, thermogenic gene expression, or circadian expression of clock genes centrally and peripherally. Mechanistically, PRCE inhibited α-amylase activity and delayed early intestinal glucose absorption. These effects were accompanied by selective remodeling of the gut microbiota, including increased abundance of Akkermansia muciniphila. We conclude that PRCE improves glucose homeostasis in established obesity through intestinal mechanisms involving reduced carbohydrate digestion, delayed glucose absorption, and selective remodeling of the gut microbiota.
Reverse transcriptase (RT)-associated RNase H (RNH) remains the only virally encoded enzymatic function of HIV-1 yet to be targeted by any drugs approved or in the development pipeline. We have previously developed 1,4-dihydroxy-1,8-napthyridinone (DHN) analogs as potent inhibitors of orthopoxvirus resolvases which belong to the RNase H-like (RNHL) nuclease family featuring a two-metal-dependent catalytic mechanism. In this work, we have enriched the in-house DHN collection to 82 analogs and tested them in HIV-1 in vitro and antiviral assays. In biochemical assays against RT, most analogs inhibited RT RNH activity with low nM to sub-μM potencies without appreciable inhibition against RT polymerase (pol) activity. Structure-activity relationship (SAR) analysis reveals that analogs bearing a phenyl at C-3 with various substitutions at C-5 position are particularly potent. Removing the N-1 hydroxyl group largely abrogated the RNH inhibition, consistent with a two-metal-chelating pharmacophore. In a cell-based antiviral assay against HIV-1 virus, many analogs exhibited sub-μM antiviral activity without significant cytotoxicity. Finally, most analogs were tested against HIV-1 integrase strand transfer (INST) activity which also belongs to the RNHL family. Although some inhibited INST with IC50 values in the low to mid μM range, the antiviral activity appears to correlate better with RT RNH inhibition.
To make adaptive decisions, it is often necessary to retrieve episodic memories, for example, about whether an item was previously associated with reward. Compared to young adults, older adults are impaired at making adaptive episodic memory-based choices. There are substantial individual differences across older adults, however. In this study, we examined whether hippocampal volume or extrahippocampal cortical thickness in the medial temporal lobe (MTL) is associated with better episodic memory-based decision making in cognitively unimpaired older adults. Older adults (n = 87; aged 61-88) completed a decision-making task and a T1-weighted anatomical MRI scan. In the task, they studied images of houses paired with arbitrary reward values ($5 or $0). Later, they made incentivized approach/avoid decisions about these items. Finally, their memory for the items and their values was assessed. MTL structural data were segmented with the ASHS-T1 pipeline to obtain volume measures for anterior and posterior hippocampus, and cortical thickness measures in entorhinal cortex, parahippocampal cortex, and perirhinal cortex Brodmann areas (BAs) 35 and 36. BA35 cortical thickness was associated with better performance in the decision-making task. This effect persisted after adjusting for memory performance, suggesting that BA35 thickness is specifically linked to the retrieval and use of episodic memories at the time of choice. Although this study is cross-sectional, it suggests that atrophy in BA35 may contribute to subtle changes in the ability to use memory to make reward-maximizing choices, even in individuals who do not yet show evident cognitive impairment.
Chronic obstructive pulmonary disease (COPD) represents a major global health burden, largely attributable to tobacco exposure, including emerging patterns such as early initiation and dual use with electronic cigarettes. Early detection through spirometry in primary care remains suboptimal, potentially limiting timely identification of early disease stages, including Pre-COPD and Preserved Ratio Impaired Spirometry (PRISm). This study aimed to assess whether the implementation of a structured, spirometry-based COPD clinic within primary care networks (Aggregazioni Funzionali Territoriali, AFTs) may be associated with improved diagnostic appropriateness, more consistent therapeutic management, and more efficient use of healthcare resources. We conducted a retrospective observational analysis of routinely collected clinical data from approximately 30,000 patients across three AFTs in the Campania Region (Italy), each including about 10,000 individuals. One AFT was equipped with a dedicated respiratory clinic providing in-house spirometry performed by trained personnel, while the other two followed standard care pathways without structured respiratory services. Key variables included spirometry utilization, diagnostic confirmation of COPD, patterns of care, and selected indicators of healthcare use. In the two standard AFTs, COPD diagnoses were not supported by spirometric confirmation in approximately 65% and 70% of cases, respectively. In contrast, the AFT with a dedicated clinic showed a substantially higher use of spirometry (approximately 80% vs. 30-35%), predominantly performed within the primary care setting. This organizational model was associated with improved alignment between diagnosis and objective testing, and with indicators suggestive of better therapeutic adherence and more appropriate use of secondary care services. The integration of structured, spirometry-enabled respiratory services within primary care networks may contribute to more appropriate COPD diagnosis and management. While the availability of spirometry alone is insufficient, organizational models that incorporate trained personnel, standardized procedures, and coordinated care pathways could represent a potentially effective approach to addressing under- and misdiagnosis in COPD.
Polyvinyl alcohol (PVA) phantoms are typically isotropic and are widely used to validate ultrasound elastography techniques for soft-tissue evaluation. However, some biological soft tissues (e.g., skeletal muscle) exhibit distinct mechanical anisotropy, which necessitates the use of anisotropic PVA phantoms for the rigorous testing of elastography methods targeting these tissues. While prior studies have noted that in-house anisotropic PVA phantoms can be fabricated via stretch-integrated freeze/thaw cycles (FTCs), critical technical details (e.g., fabrication process, quality control) remain insufficiently documented. This work presents a visually detailed, reproducible protocol for fabricating anisotropic PVA phantoms, focusing on key materials, stepwise processes, and quality controls to induce stable, uniform anisotropy. Key materials include PVA as the phantom matrix, potassium sorbate as a preservative, graphite particles as acoustic scatterers, and pure water (or deionized water) as the solvent. The fabrication process comprises three core stages: 1) Preparation of a homogeneous PVA-based solution through controlled thermal conditions to ensure complete PVA dissolution; 2) Solidification via FTCs: the cooled solution is poured into 3D-printed molds, followed by stretch-free FTCs to form a preliminary structure; 3) Inducing anisotropy via stretched FTCs: additional FTCs are performed under controlled stretching to induce directional anisotropy. Quality-control measures (e.g., avoiding air bubbles during PVA dissolution) are described in detail. After fabrication, ultrasound shear wave imaging (SWI) and uniaxial tensile testing are employed to confirm the phantom's mechanical anisotropy. This paper provides a standardized approach for fabricating anisotropic tissue-mimicking phantoms to validate ultrasound elastography techniques with enhanced accuracy and consistency.