Objective:To investigate, for multi-sensitized allergic rhinitis (AR) patients allergic to dust mites combined with other allergens (pollen, mold, animal dander, etc.), whether the single dust mite subcutaneous immunotherapy (SCIT) can improve the specific symptoms caused by other allergens in the patients, and to analyze the relationship between the effectiveness of symptom improvement in these patients and the type, quantity and severity of the allergens.Methods:A multicenter retrospective study was conducted to collect mul-sensitized AR patients from allergy or respiratory departments of 5 hospitals who received house dust mite allergen preparation SCIT for 12 to 36 months and met other inclusion and exclusion criteria from February to July 2024. General clinical data were collected and the perennial or seasonal symptoms before and after treatment were evaluated with visual analogue scale (VAS) to assess whether there was an perennial or allergen-specific symptom improvement (VAS score decrease ≥30%), by which the patients were divided into effective group and ineffective. R software was used to analyze the differences between groups by using Fisher′s exact test and Mann-Whitney U test. Results:A total of 62 patients were enrolled, and the treatment were effective in 39 of them, with an effective rate of 62.9%. For allergen-specific symptoms, the median age of the effective group was higher than that of the ineffective group (12 years old vs. 8 years old, P=0.039), and the effective rate in dust mite specific immunoglobin E (sIgE) grade ≤5 group was higher than that in sIgE grade >5 group (81.6% vs. 45.5%, P=0.008), and the effective rate of mold sIgE grade ≤2 group was higher than that of sIgE grade >2 group (83.3% vs. 28.6%, P=0.045), and there was no statistically significant correlation between the other allergen grades and the effective rate ( P>0.05). For perennial symptoms, the effective rate in the mold grade ≤2 group was higher than that in the sIgE grade >2 group (91.3% vs. 28.6%, P=0.010), and there was no statistically significant correlation between the other allergen grades and the effective rate ( P>0.05). There was no significant correlation between the treatment effectiveness of perennial or allergen-specific symptoms and the number of combined allergens, the grade of skin test, and the difference between the grade of combined allergens and that of dust mites ( P>0.05). Conclusion:Among the patients with multi-sensitized AR allergic to dust mites included in this study, single dust mite SCIT is effective in some of them, and for allergen-specific symptoms, the effective group was elder, and dust mite sIgE grade 6 and mold sIgE grade ≥2 was related to the low effective rate of SCIT. The present results are insufficient for selecting single or multiple AIT in any type of multi-sensitized patients.

The role and clinical significance of allergen-specific immunoglobulin G4 (IgG4) in allergic diseases are complex and multifaceted. IgG4, a subclass of IgG antibodies, is capable of Fab-arm exchange, allowing it to bind to double-specific antigens in a monovalent manner. IgG4 has a low binding affinity for C1q and fragment crystallizable γ, typically exhibiting non-inflammatory characteristics. The role of IgG4 in allergic diseases is controversial, but in allergen immunotherapy, IgG4 acts as a tolerance-inducing agent blocking IgE activity by competing with allergen binding, playing a protective role. However, food-specific IgG4 is considered a bystander in food allergy and should not be used as a clinical diagnostic tool. Moreover, the pathogenic role of IgG4 in diseases such as eosinophilic esophagitis has also been noted. This review summarizes the structure, function, and role of IgG4 in allergic diseases, aiming to deepen the understanding of the value of IgG4 among clinical medical workers and provide guidance for the correct application of IgG4 in clinical practice.

The role and clinical significance of allergen-specific immunoglobulin G4 (IgG4) in allergic diseases are complex and multifaceted. IgG4, a subclass of IgG antibodies, is capable of Fab-arm exchange, allowing it to bind to double-specific antigens in a monovalent manner. IgG4 has a low binding affinity for C1q and fragment crystallizable γ, typically exhibiting non-inflammatory characteristics. The role of IgG4 in allergic diseases is controversial, but in allergen immunotherapy, IgG4 acts as a tolerance-inducing agent blocking IgE activity by competing with allergen binding, playing a protective role. However, food-specific IgG4 is considered a bystander in food allergy and should not be used as a clinical diagnostic tool. Moreover, the pathogenic role of IgG4 in diseases such as eosinophilic esophagitis has also been noted. This review summarizes the structure, function, and role of IgG4 in allergic diseases, aiming to deepen the understanding of the value of IgG4 among clinical medical workers and provide guidance for the correct application of IgG4 in clinical practice.

Objective:To investigate, for multi-sensitized allergic rhinitis (AR) patients allergic to dust mites combined with other allergens (pollen, mold, animal dander, etc.), whether the single dust mite subcutaneous immunotherapy (SCIT) can improve the specific symptoms caused by other allergens in the patients, and to analyze the relationship between the effectiveness of symptom improvement in these patients and the type, quantity and severity of the allergens.Methods:A multicenter retrospective study was conducted to collect mul-sensitized AR patients from allergy or respiratory departments of 5 hospitals who received house dust mite allergen preparation SCIT for 12 to 36 months and met other inclusion and exclusion criteria from February to July 2024. General clinical data were collected and the perennial or seasonal symptoms before and after treatment were evaluated with visual analogue scale (VAS) to assess whether there was an perennial or allergen-specific symptom improvement (VAS score decrease ≥30%), by which the patients were divided into effective group and ineffective. R software was used to analyze the differences between groups by using Fisher′s exact test and Mann-Whitney U test. Results:A total of 62 patients were enrolled, and the treatment were effective in 39 of them, with an effective rate of 62.9%. For allergen-specific symptoms, the median age of the effective group was higher than that of the ineffective group (12 years old vs. 8 years old, P=0.039), and the effective rate in dust mite specific immunoglobin E (sIgE) grade ≤5 group was higher than that in sIgE grade >5 group (81.6% vs. 45.5%, P=0.008), and the effective rate of mold sIgE grade ≤2 group was higher than that of sIgE grade >2 group (83.3% vs. 28.6%, P=0.045), and there was no statistically significant correlation between the other allergen grades and the effective rate ( P>0.05). For perennial symptoms, the effective rate in the mold grade ≤2 group was higher than that in the sIgE grade >2 group (91.3% vs. 28.6%, P=0.010), and there was no statistically significant correlation between the other allergen grades and the effective rate ( P>0.05). There was no significant correlation between the treatment effectiveness of perennial or allergen-specific symptoms and the number of combined allergens, the grade of skin test, and the difference between the grade of combined allergens and that of dust mites ( P>0.05). Conclusion:Among the patients with multi-sensitized AR allergic to dust mites included in this study, single dust mite SCIT is effective in some of them, and for allergen-specific symptoms, the effective group was elder, and dust mite sIgE grade 6 and mold sIgE grade ≥2 was related to the low effective rate of SCIT. The present results are insufficient for selecting single or multiple AIT in any type of multi-sensitized patients.

Objective:To explore the association between insulin resistance (IR) and genome-wide DNA methylation based on Shanghai twin study.Methods:Monozygotic twins (MZ) from Shanghai were recruited during 2012-2013, 2017-2018, and 2022-2023. Data were collected by questionnaire survey, physical examination and laboratory tests. Genome-wide DNA methylation was quantified. Generalized linear mixed effect model was applied to analyze the association between methylation level at each site and homeostatic model assessment 2-insulin resistance (HOMA2-IR). Non-paired and paired designs were used to assess the association between DNA methylation and phenotype of IR. Cluster analysis was conducted to identify the clusters of top significant sites. Generalized linear regression was performed to examine the differential methylation patterns from clusters.Results:A total of 100 MZ pairs were included in this study. Hypermethylated cg10535199-2q23.1 ( β=0.74%, P=1.51×10 -7, OR=1.06, 95% CI: 1.03-1.09) and ch.17.49619327- SPOP ( β=0.23%, P=7.54×10 -7, OR=1.17, 95% CI: 1.08-1.28) were identified with suggestive significance. After correcting for multiple testing, no sites reached genome-wide significance. There was no statistical significance in the paired analysis. Two clusters with hypomethylated ( β=-0.39%, P<0.001) and hypermethylated ( β=0.47%, P<0.001) patterns were observed for HOMA2-IR. Conclusions:IR was significantly associated with DNA methylation, and genetic factors might contribute to the association.

Objective:To investigate the characteristics of allergen component in dust mite（DM） -induced allergic rhinitis（AR） patients, and provide reference for the diagnosis and treatment of AR. Methods:DM-induced AR patients with or without allergic asthma（AA） who visited the Allergy Department of Tongji Hospital, Huazhong University of Science and Technology between 2021 and 2022 were enrolled. Patients'age, gender, and visual analog scale（VAS） for symptoms were recorded. sIgE and sIgG4 levels of allergen components such as Der f1, Der f2, Der p1, Der p2, Der p7, Der p10, Der p21, and Der p23 were detected using a protein chip method. The sensitization characteristics of the allergen components in the patients were observed, and the correlation between sIgE, sIgG of each component and VAS as well as the component differences between AR and AR with AA（AR&AA） were evaluated. Results:A total of 87 DM-induced AR patients were enrolled, with 42.5% of them were AR&AA, their VAS scores were significantly higher than those of AR patients（6.38±1.95 vs 5.25±1.85, P=0.009 8）. The order of sensitization rates for DM components was as follows: Der p2（82.8%）, Der f2（81.6%）, Der p1（74.7%）, Der f1（70.1%）, and Der p23（35.6%）. The order of positive rates for sIgG4 was: Der p2（21.8%）, Der f2（13.8%）, Der p21（8.0%）, and Der p7（6.9%）. There were no correlation between the sIgE, sIgG4 levels or positive numbers of components and VAS scores, but there were positive correlations between sIgE, sIgG4 concentrations of components. Compared with AR patients, AR&AA patients had higher levels of sIgE for Der p（60.5[7.2-91.1]vs 14.0[4.8-45.1], P=0.02）, Der f（49.8[15.7-81.6]vs 21.3[7.0-50.2], P=0.04）, Der p1（27.2[0.7-51.5]vs 2.6[0.2-24.9], P=0.02）, Der p2（20.0[1.4-60.6]vs 5.5[0.6-19.1], P=0.004）, and Der f2（58.9[16.0-89.2]vs 23.4[0.9-56.8], P=0.009）, and a higher proportion of AR with AA patients had sIgE levels of Der p1（70.3% vs 48.0%, P=0.038） and Der p23（27.0% vs 14.0%, P=0.039） that were ≥3 grades. Conclusion:Der p1/f1, Der p2/f3, and Der p23 are the major components of DM sensitized AR patients. Multiple component sensitization and sIgE, sIgG4 levels of each component are not correlated with the severity of AR. The sIgE levels of the Der p1/f1, Der p2/f3, and Der p23 components in AR&AA patients are higher than AR.
Animals ; Humans ; Allergens ; Pyridinolcarbamate ; Rhinitis, Allergic/therapy* ; Pyroglyphidae ; Asthma ; Antigens, Dermatophagoides

OBJECTIVE To study the effects of Shenfu yixin granule on mitochondrial autophagy of cardiomyocytes in rats with heart failure after acute myocardial infarction. METHODS The model of heart failure after acute myocardial infarction was established by ligaturing the anterior descending branch of the left coronary artery in rats. The model rats were divided into model group，Shenfu yixin granule low-dose and high-dose groups （1.76，8.8 g/kg），Fosinopril sodium tablets group （positive control ，4 mg/kg），sham operation group was set up （only threading without ligation at the same position ），with 8 rats in each group. After 4 weeks of drug intervention ，the hemodynamic indexes of rats in each group were measured by physiological recorder. The pathological changes of myocardial tissue were observed in each group. The level of oxidative stress in cardiomyocytes ， mitochondrial membrane potential ，protein expression of PTEN-induced putative kinase 1（PINK1），E3 ubiquitin ligase Parkin and ubiquitin binding protein P 62 in myocardial tissue of rats in each group were detected. RESULTS Compared with sham operation group ，the pathological injuries such as myocardial fiber morphology disorder and inflammatory cell infiltration were serious. The left ventricular end systolic pressure （LVESP），maximum rate of rise of left ventricular internal pressure （+dp/dtmax）， maximun rate of decrease of left ventricular internal pressure （－dp/dtmax），total antioxidant capacity ，mitochondrial membrane potential，PINK1，Parkin and P 62 protein expression were significantly decreased in model group （P＜0.01）. The left ventricular end diastolic pressure （LVEDP），the level of reactive oxygen species and the activity of reduced nicotinamide adenine dinucleotide phosphate in left ventricular ischemic cardiomyocytes were significantly increased （P＜0.01）. Compared with model group ，the pathological injuries of myocardial tissue in intervention groups were alleviated ，and above indexes were improved in varying degrees（P＜0.01 or P＜0.05）. CONCLUSIONS Shenfu y ixin granule can reduce the level of oxidative stress and alleviate heart failure after acute myocardial infarction ，which may be related to the activation of Parkin-dependent pathway to strengthen mitochondrial autophagy and reduce mitochondrial dysfunction.

To detect the expression of galectin-13 in allergic diseases and provide a new way for the diagnosis and treatment of allergic diseases. A retrospective analysis method was used to screen 216 patients with allergic diseases with house dust mites or aspergillus as allergens who visited the Department of Allergy and Department of Respiratory of Tongji Hospital attached Tongji Medical College, Huazhong University of Science and Technology from March 2018 to May 2021. These allergic diseases included allergic asthma, allergic bronchopulmonary aspergillosis, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, allergic urticaria. 25 subjects without underlying diseases were selected as healthy controls. The galectin-13 content in serum in each group were detected, and the Pearson correlation was used to determine the correlation between the galectin-13 content in serum in each group and blood eosinophil count, blood specific IgE, the score scale of allergic disease. The expression of Galectin-13 was increased in allergic asthma group (71.44±39.44) pg/ml, allergic bronchopulmonary aspergillosis group (100.10±47.62) pg/ml, allergic rhinitis group (54.11±24.81) pg/ml and dermatitis group (44.12±19.51) pg/ml. The expression of galectin-13 was not significantly increased in allergic urticaria group (32.75±10.29) pg/ml and the allergic conjunctivitis group (30.55±9.87) pg/ml. The galectin-13 content in serum, was positively correlated with blood eosinophil count( r s=0.54, P<0.001) and house dust mite specific IgE ( r s=0.51, P<0.001) in allergic asthma group, and was positively correlated with blood eosinophil count( r s=0.63, P=0.025) and aspergillus fumigatus specific IgE ( r s=0.58, P=0.046) in allergic bronchopulmonary aspergillosis group. It was positively correlated with blood eosinophil count ( r s=0.52, P=0.000 2) and house dust mite specific IgE ( r s=0.41, P=0.005) in allergic rhinitis group. In allergic conjunctivitis group, the expression of galectin-13 was positively correlated with conjunctivitis symptom score ( r s=0.47, P=0.048). In atopic dermatitis group, the expression of galectin-13 was positively correlated with blood eosinophil count ( r s=0.58, P<0.001) and house dust mite specificity IgE ( r s=0.47, P=0.002). In allergic urticaria group, the expression of galectin-13 was not significantly correlated with blood eosinophil count or house dust mite specific IgE. Galectin-13 may be related to the occurrence and progress of allergic diseases and may be involved in the occurrence of eosinophilic inflammation.

To detect the expression of galectin-13 in allergic diseases and provide a new way for the diagnosis and treatment of allergic diseases. A retrospective analysis method was used to screen 216 patients with allergic diseases with house dust mites or aspergillus as allergens who visited the Department of Allergy and Department of Respiratory of Tongji Hospital attached Tongji Medical College, Huazhong University of Science and Technology from March 2018 to May 2021. These allergic diseases included allergic asthma, allergic bronchopulmonary aspergillosis, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, allergic urticaria. 25 subjects without underlying diseases were selected as healthy controls. The galectin-13 content in serum in each group were detected, and the Pearson correlation was used to determine the correlation between the galectin-13 content in serum in each group and blood eosinophil count, blood specific IgE, the score scale of allergic disease. The expression of Galectin-13 was increased in allergic asthma group (71.44±39.44) pg/ml, allergic bronchopulmonary aspergillosis group (100.10±47.62) pg/ml, allergic rhinitis group (54.11±24.81) pg/ml and dermatitis group (44.12±19.51) pg/ml. The expression of galectin-13 was not significantly increased in allergic urticaria group (32.75±10.29) pg/ml and the allergic conjunctivitis group (30.55±9.87) pg/ml. The galectin-13 content in serum, was positively correlated with blood eosinophil count( r s=0.54, P<0.001) and house dust mite specific IgE ( r s=0.51, P<0.001) in allergic asthma group, and was positively correlated with blood eosinophil count( r s=0.63, P=0.025) and aspergillus fumigatus specific IgE ( r s=0.58, P=0.046) in allergic bronchopulmonary aspergillosis group. It was positively correlated with blood eosinophil count ( r s=0.52, P=0.000 2) and house dust mite specific IgE ( r s=0.41, P=0.005) in allergic rhinitis group. In allergic conjunctivitis group, the expression of galectin-13 was positively correlated with conjunctivitis symptom score ( r s=0.47, P=0.048). In atopic dermatitis group, the expression of galectin-13 was positively correlated with blood eosinophil count ( r s=0.58, P<0.001) and house dust mite specificity IgE ( r s=0.47, P=0.002). In allergic urticaria group, the expression of galectin-13 was not significantly correlated with blood eosinophil count or house dust mite specific IgE. Galectin-13 may be related to the occurrence and progress of allergic diseases and may be involved in the occurrence of eosinophilic inflammation.

Allergic diseases have serious influence on human health and quality of life. Cytokines secreted by T-helper cell type 2 (Th2), such as interleukin (IL)-4 and IL-13, play a pivotal role in the pathogenesis of allergic diseases. By recognizing and binding to IL-4 and IL-13 receptors, dupilumab can block the signal transduction pathways of IL-4 and IL-13, inhibit Th2 inflammatory reaction, and thus play a therapeutic role in allergic diseases. At present, dupilumab has been on the market in many countries and regions around the world, yet with different indications approved, mainly including atopic dermatitis, moderate-to-severe eosinophilic asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, etc. In addition, this drug may also have better curative effect on IgE-mediated allergic reactions and other dermal diseases. Meanwhile, the safety profile of dupilumab is generally good and the common adverse reactions mainly include injection site reactions (pain, ecchymosis and swelling at the injection site), ocular diseases (conjunctivitis, keratitis, itchiness of eyes and dry eyes), oral herpes, headache, and other herpes simplex virus infections. In China, dupilumab has been approved for the treatment of moderate-to-severe atopic dermatitis in patients aged ≥6 years, showing good efficacy and no obvious safety problems.