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.
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。.
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。.
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.
Therapy-induced senescence (TIS) is a major component of tumor cell response to a variety of anticancer treatments in preclinical models. Most TIS-related literature is derived from 2D-based studies with limited evidence in 3D models. This study aimed to investigate the challenges of developing an in-house (DIY) 3D bioprinted TIS cell model. A conventional thermoplastic extrusion-based 3D printer (Anet A8 kit) was modified to function as a bioprinter, enabling the fabrication of a Caco2 cell model via extrusion-based bioprinting. The printed 3D models were exposed to doxorubicin (DOX, at 1 and 10 μM), a well-established TIS trigger, and then assessed for senescence-associated β-galactosidase (SA-β-gal) activity and gene expression of several senescence regulators and components of the senescence-associated secretory phenotype (SASP) via real-time PCR. Treated cells exhibited increased SA-β-gal staining and increased expression of CDKN2A and CDKN2B (and modestly TP53). Furthermore, the expression of SASP-related genes, including MMP3, MMP9, CXCL8, and TGF-β1 (but not IL-1A), was increased, albeit non-significantly, suggesting a potential opportunity to detect transcriptional SASP changes in 3D bioprinted tumor cell models. This study provides an early attempt to develop a TIS 3D bioprinted tumor cell model, highlighting several challenges, including infrequent nozzle clogging, difficulty of image-based quantification of SA-β-gal staining, and inter-print variation in gene expression profiles. In-house DIY 3D bioprinting for investigating tumor cell senescence is feasible but requires further improvement prior to use in senolytic screening.
This article describes the federal Medicaid Institutions for Mental Diseases (IMD) exclusion and compares legislative proposals introduced in the 119th Congress-House of Representatives Bill (H.R.) 5662 and H.R. 6727-that seek to repeal this policy. A descriptive policy analysis was conducted using publicly available legislative texts, related federal policy documents, and earlier reviews examining potential impacts of the repeal of the IMD exclusion. The analysis summarizes the statutory basis of the IMD exclusion, reviews existing workarounds, and compares the key mechanisms proposed in H.R. 5662 and H.R. 6727. Potential implications for Medicaid financing and inpatient psychiatric capacity are discussed. The IMD exclusion prohibits federal Medicaid reimbursement for most inpatient psychiatric facilities with more than 16 beds for adults aged 21-64 years, contributing to reliance on state financing and temporary waiver programs. Both H.R. 5662 and H.R. 6727 propose repealing this exclusion. H.R. 5662 would repeal the policy without additional requirements, while H.R. 6727 would also require the U.S. Department of Health and Human Services to establish standards for participating facilities. Repeal would expand eligibility for federal Medicaid funding but would not mandate changes in state utilization or capacity. Recent legislative efforts to repeal the IMD exclusion reflect a growing concern regarding inpatient psychiatric bed shortages and mental health system strain. Understanding the differences between proposed repeal strategies is essential for evaluating how changes in Medicaid financing could affect inpatient psychiatric care and broader behavioral health systems.
The sensitization mechanisms driving allergic airway disease progression from allergic rhinitis (AR) to asthma (AS) in children remain incompletely understood. This study investigated age-related patterns and topological network heterogeneity of allergen sensitization between these airway phenotypes. In this retrospective cross-sectional study, 2193 children with AR or AS were enrolled. Propensity score matching (PSM) was utilized to control for age, yielding a 1:1 matched cohort of 1206 patients. The topological architecture of allergen co-sensitization was reconstructed using an Ising probability graphical model. Independent risk factors for lower airway involvement were identified via multivariable logistic regression. House dust mites mix (41%), cat dander (17%), and tree pollen mix (9.5%) dominated inhalant sensitizations. Egg white (22%), cow's milk (20%), and lamb (19%) were the most prevalent food sensitizations. While inhalant sensitization exhibited homogenous age-dependent increases in both groups, foodborne immune tolerance showed profound heterogeneity. By adolescence (≥12 years), the risk of sensitization to milk and egg white was 5.64-fold (OR = 5.64, 95% CI: 1.47-21.69, p = 0.010) and 3.40-fold (OR = 3.40, 95% CI: 1.07-10.07, p = 0.029) higher than in the AR group. Ising network analysis revealed a highly compartmentalized modular structure in AR, whereas the AS network exhibited significant complexity and deep cross-system connectivity, with peanut acting as a topological hub bridging core indoor inhalants. Multivariable regression demonstrated cockroach (aOR: 2.70; 95% CI: 1.11-7.57; p=0.039) and peanut (aOR: 1.86; 95% CI: 1.02-3.47; p=0.046) sensitizations were independent risk factors for lower airway involvement. Children with AS demonstrate a more complex cross-sensitization network than those with AR, rather than simply a higher burden of inhalant allergies. The delayed resolution of food sensitizations serves as a critical differentiator for the AS phenotype, highlighting the necessity of monitoring food allergies in pediatric airway disease management.
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.
In Ethiopia, there are many forms of art in the area of local alcoholic fermentation. Beverages made locally using indigenous knowledge are known as traditional fermented alcoholic beverages. Local fermented alcoholic beverages are consumed by diverse ethnic groups in the country. Different traditional beverages made with fermentation in Ethiopia, such as Shameta, Borde, Imbushbush, Winetej, Tella, Tej, Keribo, Korefe, Buqri, Duka, and distilled spirits such as Katikala or Areke. Traditional Tella and Areke alcoholic beverages are the most popular homemade beverages, made on a small scale and sold by local alcohol vendors from their houses. The process of fermentation is uncontrolled, spontaneous, and natural. The most common microorganisms found during the fermentation of these indigenous alcoholic beverages are lactic acid bacteria and yeasts. Areke is a locally produced distilled alcoholic beverage produced from the results of fermentation that are made almost identically to Tella with the exception of the fermentation mass. The three fundamental steps in the Tella preparation procedure such as "tenses," "difdif," and "Tella." The growing interest in traditional and functional beverages worldwide promises upgrading and commercialization of Areke and Tella by standardizing the processes, which could create local employment, generate income, and promote cultural tourism. However, challenges such as a lack of standardization, inconsistent quality, and insufficient scientific evidence must be addressed. To transition these traditional beverages into industrial production, further research is required. This review summarizes scientific information on indigenous knowledge, processing methods, microbial dynamics, metabolic profiling, functional properties, and the future commercial potential of Areke and Tella, traditional fermented beverages in Ethiopia.
This study evaluated the effects of partially replacing groundnut cake with soaked chickpea (Cicer arietinum L.) seeds, with or without enzyme supplementation, on growth performance, carcass traits, serum biochemical indices, and intestinal histopathology of broiler chickens. A total of 200 day-old unsexed Ross 308 chicks (initial body weight: 39.5 ± 0.17 g) were randomly assigned to five dietary treatments, each with four replicates of ten birds each in a completely randomized design. The experimental diets included a control diet without chickpea seeds and diets in which 45% and 60% of groundnut cake were replaced with soaked chickpea seeds, with or without enzyme supplementation. All birds were fed isocaloric and isonitrogenous diets during the starter (1 to 3 weeks) and finisher (4 to 6 weeks) phases, and reared in an open-sided poultry house. Overall body weight gain and feed intake were not significantly affected (P ≥ 0.05) by the dietary treatments. However, feed conversion ratio (FCR) was significantly (P ≤ 0.05) worsened in birds fed chickpea-based diets compared with the control. Enzyme supplementation did not significantly improve growth performance across all phases. Serum cholesterol was significantly (P ≤ 0.05) reduced in birds fed diets containing 60% chickpea replacement, while enzyme supplementation had no significant (P ≥ 0.05) effect. Histopathological examination revealed mild to moderate alterations in liver and intestinal tissues at higher inclusion levels, particularly in diets without enzyme supplementation. In conclusion, soaked chickpea seeds can replace up to 45% of groundnut cake in broiler diets, however, higher inclusion levels may impair feed efficiency and health status. Higher inclusion levels may compromise feed efficiency and intestinal integrity, even with enzyme supplementation.
Cyclin-dependent kinase 1 (CDK1) has emerged as a compelling target for anticancer drug development due to its essential role in cell cycle regulation. In this study, a series of pyrazolopyrimidine-based inhibitors was investigated through an integrated computational approach that combined molecular docking, three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling, and molecular dynamics simulations. CoMFA and CoMSIA models were established to elucidate the structural features influencing CDK1 inhibition, demonstrating high reliability with q² and r² values of 0.58 and 0.945, respectively. Docking studies using the crystal structure of CDK1 (PDB ID: 4Y72) revealed key interactions and hotspot residues, such as L83, V18, and D86, which contribute significantly to ligand binding. From a library of 100 in-house compounds, compounds 34 and 37 exhibited strong binding affinities (-12.61 and -12.50 kcal/mol) and were further evaluated through molecular dynamics simulations. The stability of these complexes was supported by RMSD analysis and binding free energy calculations (-94.99 kcal/mol for compound 34). Moreover, ADMET profiling indicated favorable pharmacokinetic properties and synthetic accessibility. These findings offer critical insights into the structural determinants of CDK1 inhibition and support the further development of pyrazolopyrimidine scaffolds as potential anticancer agents.
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.
Objective: To investigate predictive indicators for early efficacy of cluster immunotherapy in patients with allergic asthma (AS) in Northeast China. Methods: A single-center self-controlled before-and-after study was conducted to collect data from 93 patients with allergic asthma primarily induced by dust mite allergy. These patients underwent cluster immunotherapy at the Allergy Clinic of Northern Theater Command General Hospital from October 2022 to October 2024. There were 58 males and 35 females, aged 12-60 years (median: 16.00 years; mean: 24.20 years). Relevant clinical scales were collected at baseline (T0) and 6 months post-treatment (T1).Based on GINA(Global Initiative for Asthma) guidelines,the controlled/partially controlled patients were included in the Effective group and uncontrolled patients were included in the ineffective group. Factors potentially influencing early SCIT (subcutaneous immunotherapy) efficacy in dust mite-allergic asthma patients were collected. Internal validation was performed using the Bootstrap sampling method in R software. To ensure the robustness of the findings, sensitivity analyses were conducted to evaluate the stability of the primary conclusions. Results: Among the 93 enrolled patients, significant improvements were observed in ACT, ACQ, VAS, and TMS scores at T1 compared to T0 (all P<0.001). Univariate analysis indicated that gender (χ2=4.468, P=0.035), ACT(asthma control test) score(Z=5.42, P<0.001), VAS(visual analogue scale) score(Z=2.463, P=0.014), TMS(total medicine score) score(Z=3.146, P=0.002), FVC%pred(The percent predicted value of the forced vital capacity)(Z=-2.339, P=0.019), Dp-sIgE(Dermatophagoides pteronyssinus-specific immunoglobulin E) (Z=4.275, P<0.001), Dp-sIgE/tIgE ratio (%) (Z=6.036, P=0.003), and Df-sIgE(Dermatophagoides farinae-specific immunoglobulin E)/tIgE ratio (%) (Z=3.052, P=0.002) were associated with early efficacy (all P<0.05). Multivariate analysis identified gender, ACT score (OR: 0.189, 95%CI: 0.066-0.545) and Dp-sIgE/tIgE ratio (%) (OR: 1.474, 95%CI: 1.234-1.76) as independent predictors (all P<0.05). ROC curve analysis showed that the combined prediction model of the three had the best efficacy(AUC=0.93, 95%CI: 0.89-0.93). Using the Dp-sIgE/tIgE ratio alone, the AUC was 0.86, with an optimal cut-off value of 10.32%, sensitivity of 69%, and specificity of 97%. After internal validation by Bootstrap, the AUC for the Dp-sIgE/tIgE ratio was 0.864±0.035 (95%CI: 0.794-0.930), demonstrating good stability. Validation of the combined model resulted in an AUC of 0.940±0.020 (95%CI: 0.890-0.980), further confirming the model's reliability. Sensitivity analysis, adjusting outcome grouping to complete control versus non-complete control, indicated that the ACT score (OR=0.293, 95%CI: 0.102-0.840) and the Dp-sIgE/tIgE ratio (OR=1.024, 95%CI: 1.001-1.046) remained independent predictors of treatment efficacy (P<0.05). The AUC for univariate prediction was 0.720, whereas the combined prediction AUC increased to 0.800, underscoring the robustness and reliability of the results. Conclusion: Cluster immunotherapy demonstrates favorable short-term efficacy in patients with mild to moderate allergic asthma primarily triggered by house dust mites. Female gender, ACT score, and Dp-sIgE/tIgE ratio (%) are independent predictors of early treatment response in this patient population. The combined predictive model exhibits superior efficacy in predicting treatment outcomes. Additionally, the Dp-sIgE/tIgE ratio alone serves as an effective single-factor predictor, showing stable performance in internal validation. Both methods provide valuable insights for evaluating early treatment outcomes in patients with mild to moderate dust mite-induced allergic asthma undergoing standardized. 目的： 探讨东北地区过敏性哮喘（AS）患者集群免疫治疗早期疗效的预测指标。 方法： 采取单中心治疗前后自身对照研究的方法，收集2022年10月至2024年10月期间北部战区总医院过敏反应门诊确诊为以尘螨过敏为主，并进行集群免疫治疗的过敏性哮喘患者共93例，男性58例，女性35例，年龄范围12~60岁、中位数16.00岁、平均24.20岁，分别于治疗前（T0期）、治疗6个月后（T1期）收集临床量表数据；根据全球哮喘防治创议（GINA）指南的哮喘控制水平，将控制/部分控制患者纳入有效组，未控制患者纳入无效组，收集可能影响皮下特异性免疫治疗（SCIT）早期疗效的相关因素，采用R软件Bootstrap 抽样方法进行内部验证。为进一步验证本研究核心分析结论的稳定性与可信度，评估分组对研究结果的潜在影响，本文引入敏感性分析，以确保研究发现的稳健性。 结果： 入选93例患者中，集群免疫治疗后T1期ACT（哮喘控制测试评分）、ACQ（哮喘控制问卷）、VAS（视觉模拟评分）、TMS（总用药评分）较T0期均显著改善（均P<0.001）；单因素分析显示性别（χ2=4.468，P=0.035）、ACT评分（Z=-5.42，P<0.001）、VAS评分（Z=-2.463，P=0.014）、TMS评分（Z=-3.146，P=0.002）、FVC%pred（用力肺活量占预计值百分比）（Z=-2.339，P=0.019）、Dp-sIgE（屋尘螨特异性免疫球蛋白E）（Z=-4.275，P<0.001）、Dp-sIgE/tIgE比值（%）（Z=-6.036，P=0.003）、Df-sIgE/tIgE比值（%）（Z=-3.052，P=0.002）可能是影响早期疗效的因素（均P<0.05）。二元多因素logistic回归分析显示性别、ACT评分（OR：0.189，95%CI：0.066~0.545）、Dp-sIgE/tIgE比值（%）（OR：1.474，95%CI：1.234~1.76）是临床早期疗效的独立影响因素（均P<0.05）。ROC曲线分析显示，三者联合预测模型效能最佳（AUC=0.93，95%CI：0.89~0.93）；Dp-sIgE/tIgE比值单独预测时，AUC为0.86，其最佳cut-off值为10.32%，敏感度为69%，特异度为97%。经Bootstrap内部验证后，Dp-sIgE/tIgE比值验证后AUC=0.864±0.035，95%CI：0.794~0.930；联合模型验证后AUC=0.940±0.020，95%CI：0.890~0.980，二者均表现出良好的稳定性。敏感度分析（调整结局分组为完全控制 vs. 非完全控制）显示：ACT评分（OR=0.293，95%CI：0.102~0.840）、Dp-sIgE/tIgE比值（OR=1.024，95%CI：1.001~1.046）仍为疗效独立影响因素（P<0.05），相应单独预测AUC=0.720，联合预测AUC=0.800，结果稳健可靠。 结论： 集群免疫治疗对以尘螨过敏为主的轻中度过敏性哮喘患者具有良好的短期疗效；性别、ACT评分、Dp-sIgE/tIgE比值（%）是该类患者早期疗效的独立影响因素。联合预测模型在疗效预测上更具优势，同时Dp-sIgE/tIgE比值作为单因素也可有效预测疗效，且经内部验证稳定性良好，二者可为完成规范集群免疫治疗的轻中度、尘螨致敏过敏性哮喘患者的早期疗效评估提供有效参考。.
Sepsis is caused by a dysregulated host response to infection, characterized by multiorgan failure in which the lung is the primary target. Although matrix metalloproteinase-9 (MMP9), a macrophage-derived protease, is known to degrade extracellular matrix proteins during inflammation, its specific role in sepsis-induced lung injury (SALI) remains to be elucidated. This study elucidates the protective function of MMP9 in SALI and validated its translational potential as an early diagnostic biomarker that integrates coagulation-inflammation crosstalk. First, we integrated human blood bulk RNA-seq data and an in-house LPS-induced murine ALI model to extract coagulation-related sepsis DEGs (Cos-Gs), constructed a PPI network, and applied two-sample Mendelian randomization (MR), which identified MMP9 as a causal protection gene. Additionally, we performed molecular docking using the ZDOCK server and 100 ns molecular dynamics simulations with Gromacs to explore the interaction between MMP9 and fibrinogen. Next, in vivo studies using CLP-operated MMP9-/- and WT mice demonstrated that MMP9 deficiency reduced survival, increased pulmonary fibrinogen accumulation, and elevated IL-6/TNF-α release. Furthermore, in macrophages, fibrinogen synergized with LPS to amplify cytokines via MAPK hyperactivation, a process that was suppressed by rmMMP9 through fibrinogen degradation and subsequent MAPK inhibition. Molecular docking results showed a ZDOCK score of 1845.832 for the interaction between MMP9 and the fibrinogen α-chain, and the 100 ns molecular dynamics simulations confirmed the MMP9-α-chain complex maintained stable RMSD (0.4 to 0.5 nm) in a low-energy state. Finally, The ROC/XGBoost-SHAP models confirmed that MMP9 (AUC = 0.711) was the dominant predictor of SALI, outperforming IL-6 and matching TNF-α/CRP with external nomogram validation. Collectively, our findings indicated that MMP9 protects against SALI by suppressing fibrin-driven MAPK hyperactivation and cytokine release through its fibrinolytic activity, thereby establishing MMMP9 as a mechanistically grounded biomarker for early risk stratification.
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.