OBJECTIVES: To investigate the therapeutic effects and mechanisms of 2,6-dimethoxy-1,4-benzoquinone (2,6-DMBQ) in a mouse model of asthma. METHODS: SPF-grade BALB/c mice were randomly divided into 7 groups (n=8 each group): normal control group, ovalbumin (OVA) group, dimethyl sulfoxide+corn oil group, budesonide (BUD) group, and low, medium, and high dose 2,6-DMBQ groups. An asthma mouse model was established by OVA induction, followed by corresponding drug interventions. Non-invasive lung function tests were performed to measure airway hyperresponsiveness, and enzyme-linked immunosorbent assay was used to determine levels of interleukin (IL)-17, IL-10, and serum immunoglobulin E in bronchoalveolar lavage fluid. A cell counter was employed to detect eosinophil counts in bronchoalveolar lavage fluid, while hematoxylin-eosin staining and periodic acid-Schiff staining were used to assess lung tissue pathological changes. Western blot was conducted to examine the expression of proteins related to the mammalian target of rapamycin pathway (p-AKT/AKT and p-p70S6K/p70S6K), and a fully automated biochemical analyzer was used to evaluate liver and kidney functions. RESULTS: Compared with the normal control group, the OVA group showed increased enhanced pause values, inflammation scores from hematoxylin-eosin staining, positive area from periodic acid-Schiff staining, percentage of eosinophils, IL-17/IL-10 ratio, serum immunoglobulin E levels, and relative expression levels of p-AKT/AKT and p-p70S6K/p70S6K (P<0.05). The BUD group and the medium and high dose 2,6-DMBQ groups exhibited decreased values for these indicators compared to the OVA group (P<0.05). CONCLUSIONS 2,6-DMBQ can inhibit the mTOR pathway to alleviate airway inflammation in asthmatic mice, possibly by mitigating the imbalance between Th17 and regulatory T cells.
Animals ; Asthma/pathology* ; Mice, Inbred BALB C ; Signal Transduction/drug effects* ; Mice ; TOR Serine-Threonine Kinases/physiology* ; Female ; Benzoquinones/pharmacology* ; Immunoglobulin E/blood* ; Interleukin-10/analysis* ; Interleukin-17/analysis* ; Bronchoalveolar Lavage Fluid ; Lung/pathology*

OBJECTIVES: To explore the lipidomic characteristics of children with bronchial asthma (hereafter referred to as asthma) and identify potential biomarkers for asthma. METHODS: A total of 26 asthmatic children were prospectively enrolled as the asthma group, and 20 healthy children served as the healthy control group. The asthma group was further divided into atopic (n=13) and non-atopic (n=13) subgroups based on IgE levels. Serum lipid metabolites were analyzed using liquid chromatography-mass spectrometry, followed by statistical analysis and data visualization. RESULTS: A total of 1 435 lipids were detected in the 46 children, primarily glycerophospholipids (625/1 435, 43.55%). Significant differences were observed in serum lipid profiles between the asthma and control groups. Twelve significantly differential lipids were identified, with receiver operating characteristic curve analysis showing that phosphatidylserine (PS)(18:0/20:4) and ceramide (Cer)(c16:0) exhibited the highest diagnostic value for asthma. The relative abundances of PS(18:0/20:4) and PS(18:0/22:6) were higher in the atopic subgroup than in the non-atopic subgroup (P<0.05) and positively correlated with total IgE levels in asthmatic children (r=0.675 and 0.740, respectively; P<0.05). CONCLUSIONS Asthmatic children exhibit significant lipid metabolic disturbances, primarily characterized by abnormal glycerophospholipid metabolism. Among these, PS(18:0/20:4) and Cer(c16:0) demonstrate specific alterations and may serve as potential diagnostic biomarkers for asthma. Furthermore, the positive correlation between PS(18:0/20:4) and PS(18:0/22:6) levels and serum total IgE suggests their possible involvement in immune regulation in asthma.
Humans ; Asthma/metabolism* ; Male ; Child ; Female ; Prospective Studies ; Mass Spectrometry/methods* ; Lipids/blood* ; Chromatography, Liquid/methods* ; Child, Preschool ; Immunoglobulin E/blood* ; Biomarkers/blood* ; Adolescent ; Liquid Chromatography-Mass Spectrometry

OBJECTIVES: To investigate the clinical and immunological features of children with primary immune thrombocytopenia (pITP) or connective tissue disease (CTD) with thrombocytopenia as the initial manifestation at initial diagnosis, and to provide a basis for early differentiation. METHODS: A retrospective study was performed on 236 children with pITP (pITP group) or CTD with thrombocytopenia as the initial manifestation (CTD-TP group) who were admitted from January 2019 to August 2024. Clinical and immunological indicators were compared between the two groups to identify potential influencing factors for early differentiation and their discriminative validity. RESULTS: Compared with the pITP group, the CTD-TP group had a significantly older age of onset and significantly lower leukocyte count, eosinophil count, lymphocyte count, and complement C4 level (P<0.05), as well as significantly higher levels of C-reactive protein, IgE, and IgM (P<0.05). The logistic regression analysis showed that age, IgE, IgM, total B cells, and complement C4 were predictive factors for early differentiation between pITP and CTD-TP (P<0.05). The receiver operating characteristic curve analysis showed that a combination of these five factors had a good discriminative validity, with an area under the curve of 0.944. The correlation analysis showed a negative correlation between IgG and platelet count in the pITP group (r_s=-0.363, P<0.05) and a positive correlation between NK cells and platelet count in the CTD-TP group (r_s=0.713, P<0.05). CONCLUSIONS There is heterogeneity in the clinical and immunological indicators between children with pITP and CTD-TP at initial diagnosis, and these research findings can help with the early differentiation between the two diseases.
Purpura, Thrombocytopenic, Idiopathic/immunology* ; Diagnosis, Differential ; Connective Tissue Diseases/immunology* ; Retrospective Studies ; Early Diagnosis ; Age of Onset ; Leukocyte Count ; Complement C4/immunology* ; C-Reactive Protein/immunology* ; Immunoglobulin E/immunology* ; Immunoglobulin M/immunology* ; Humans ; Male ; Female ; Infant ; Child, Preschool ; Child ; Adolescent ; Biomarkers/blood*

OBJECTIVES: This study aimed to explore the therapeutic effect and mechanism of ginsenoside Rb3 on experimental periodontitis and bone resorption in rats. METHODS: Male SD rats were randomly divided into a control group, a ligation group, an Rb3 group, and a doxycycline (Dox) group for in vivo experiments. A periodontitis model was established by ligating the maxillary second molar, and samples were collected after 3 weeks of drug treatment. Micro-CT assessment of alveolar bone resorption was performed, and hematoxylin-eosin (HE) staining was used to observe pathological changes in periodontal and visceral tissues. Tartrate resistant acid phosphatase (TRAP) staining was applied to detect the formation of osteoclasts in periodontal tissues, and enzyme-linked immunosorbent assay (ELISA) was adopted to detect the serum levels of interleukin (IL)-6, IL-8, immunoglobulin (Ig)M, and IgG. Quantitative polymerase chain reaction (qPCR) was employed to detect the expression of factors related to gingival inflammation and osteoclast formation. Immunofluorescence staining was used to detect phospho-extracellular signal-regulated kinase (p-ERK) expression. In vitro experiments were conducted by pretreating RAW264.7 cells with drugs and adding lipopolysaccharides (LPS) stimulation from Porphyromonas gingivalis (P. gingivalis). IL-1β and IL-6 mRNA expression was detected by qPCR, and Western blot was used to detect the effect of Rb3 on the mitogen-activated protein kinases (MAPKs) signaling pathway. RESULTS: Compared with the control group, the ligation group showed significant periodontitis and bone resorption. Compared with the ligation group, the Rb3 group showed a decrease in alveolar bone resorption and osteoclast formation; p-ERK/ERK ratio, IL-1β, IL-6, and nuclear factor of activated T cells (NFATc1) mRNA levels and downstream gene expression in periodontal tissues; serum IL-6, IL-8, IgG, and IgM levels. Rb3 reduced IL-8 and IL-1β mRNA expression levels and p-ERK/ERK and p-p38 MAPK/p38 MAPK ratios in RAW264.7 cells induced by P. gingivalis LPS stimulation. CONCLUSIONS Rb3 inhibits inflammation and bone resorption in experimental periodontitis in rats. Compared with Dox, Rb3 has better effects in inhibiting pro-inflammatory factors and osteoclast gene expression and may exert anti-inflammatory effects by activating the MAPK signaling pathway.
Animals ; Ginsenosides/therapeutic use* ; Rats, Sprague-Dawley ; Male ; Periodontitis/pathology* ; Rats ; Osteoclasts/drug effects* ; Interleukin-1beta/metabolism* ; Interleukin-6/blood* ; Mice ; Alveolar Bone Loss ; Interleukin-8/blood* ; Immunoglobulin G/blood* ; RAW 264.7 Cells ; Transcription Factors

In this study, we constructed a series of recombinant Fc variants of immunoglobulin G4 (IgG4), screened the fragment crystallizable (Fc) variants with significantly prolonged serum half-lives, and analyzed the relationship between mutation site and half-life, aiming to provide a theoretical basis for the development of IgG4 antibodies and Fc fusion protein-based drugs. Nine gene sites were selected for mutation, and different mutation sites were combined. The variant expression plasmids pET24b-Fc were constructed by molecular cloning and point mutation. The plasmids were transformed into Escherichia coli BL21(DE3) for the expression of different recombinant proteins of Fc. Fc2 and Fc3 variants had slightly lower recombinant protein yields, and the expression of other variants was not affected. The toxicity of different Fc variants was determined by cell counting kit-8 (CCK-8) and calcein acetoxymethyl ester/ propidium iodide (calcein AM/PI) in vitro and enzyme-linked immuno sorbent assay (ELISA) in vivo. The results showed that the recombinant Fc variants had good biocompatibility and safety. Finally, the Fc variants were labeled with fluorescent markers, and the effects of different mutations on their serum half-lives were investigated by in vivo experiments. The Fc5 variant with prolonged serum half-life was successfully screened out, which provided a theoretical and practical basis for the optimal design of IgG4 subtype antibody and Fc fusion protein drugs.
Immunoglobulin G/blood* ; Immunoglobulin Fc Fragments/biosynthesis* ; Half-Life ; Animals ; Escherichia coli/metabolism* ; Humans ; Recombinant Fusion Proteins/biosynthesis* ; Recombinant Proteins/biosynthesis* ; Mice

OBJECTIVE: To analyze the origin and influencing factors the titer of ABO blood group antibody in neonates. METHODS: A total of 303 newborn blood samples collected in our hospital from August 2023 to March 2024 were selected for the detection of ABO blood group settings and the determination of the total titers of IgG and IgM blood group antibodies in plasma. IgM antibodies were treated with dithithreitol (DTT) to determine the titers of IgG antibodies. The total titer of the blood group antibody was compared with that of the IgG antibody. The clinical data of mothers and newborns were collected, and the correlation between the antibody titer and these clinical data was analyzed. RESULTS: Among the 303 newborn specimens, 14 cases (4.62%) were identified to possess blood group antibodies. The influence of the maternal ABO blood group on the generation of high-potency blood group antibodies in newborns was observed to follow the order of O>B>A>AB, with a significant statistical difference ( P < 0.01). Of the 123 (40.59%) newborns born to mothers of type O, 121 (98.37%) had blood group antibody titers > 2. Of the 20 (6.60%) newborns born to mothers of type AB, all 20 (100.00%) had blood group antibody titers < 2. Among 89 (29.37%) mothers of type A and 71 (23.43%) mothers of type B, the titer of 100% newborn blood group antibody was less than 2, when the newborn blood group was incompatible with the mother's blood group; the titer of the newborn blood type antibody was higher or lower, when the newborn blood type was compatible with the mother's blood type. The titer of the newborn blood group antibodies is related to the number of pregnancies of the mothers and has no association with other clinical data (such as the mother's number of obortions), the number of production, fetal gestation age. CONCLUSION The majority of ABO blood group antibodies in neonates are IgG antibodies from the mothers, and few are produced by the neonates themselves. In some neonates, IgG anti-A and/or anti-B can agglutinate with anti-stereotyped cells at room temperature. The maternal ABO blood type is the primary factor influencing the titer of the newborn blood type. The number of maternal pregnancies is a factor affecting the high titer ABO blood group antibodies in newborns.
Humans ; Infant, Newborn ; ABO Blood-Group System/immunology* ; Female ; Immunoglobulin G/blood* ; Immunoglobulin M/blood* ; Pregnancy ; Blood Grouping and Crossmatching

OBJECTIVE: To investigate the serological prevalence of high-titer IgG antibodies against 2019-nCoV among voluntary blood donors in Zunyi. METHODS: The blood plasma specimens were diluted at 1∶160 or 1∶320, then tested for the presence of 2019-nCoV IgG antibodies by using an indirect enzyme-linked immunosorbent assay(ELISA). The differences of antibody reactive rate among different genders, ages, and blood types were analyzed. RESULTS: 1 523 reactive specimens were identified in 5 378 specimens which were diluted at a ratio of 1∶160. Similarly, 329 reactive specimens were identified in 2 988 diluted at 1∶320. The overall reactive rate for antibodies was 22.1%. It was observed that females, individuals over the age of 40, and those with blood type AB exhibited higher high-titer antibody reactive rate. CONCLUSION After entering a new stage of 2019-nCoV infection prevention and control, there is a relatively high detection rate of high-titer 2019-nCoV IgG antibodies among voluntary blood donors in Zunyi. The reactive rate of antibodies varies among different genders, ages, and blood types.
Humans ; Blood Donors ; Immunoglobulin G/blood* ; Antibodies, Viral/blood* ; SARS-CoV-2/immunology* ; COVID-19 ; Female ; Enzyme-Linked Immunosorbent Assay ; Adult ; China ; Male ; Middle Aged

BACKGROUND: Epstein-Barr (EB) virus infection stimulates the production of vascular endothelial growth factor (VEGF), which contributes to the progression of angiogenesis. Angiogenesis plays an important role in the development of atherosclerosis. Since serum anti-early antigen EB virus IgG (EBV EA-IgG) titer is a sign of active EB virus infection, EBV EA-IgG titer could be associated with atherosclerosis. The number of minor (T) alleles in VEGF polymorphism rs3025039 has been reported to be inversely associated with serum VEGF concentration, suggesting that rs3025039 might have a strong influence on the association between EBV EA-IgG titer and atherosclerosis. By focusing on the role of VEGF in the development of atherosclerosis, this study aimed to investigate the association between active EB virus infection and atherosclerosis. METHODS: A cross-sectional study of 2,661 older Japanese individuals aged 60-89 years who participated in annual health check-ups during 2017-2019 was conducted. Logistic regression was used to evaluate the association between EBV EA-IgG titer and atherosclerosis in relation to rs3025039 genotype. The influence of rs3025039 (T) allele carrier status on the association between EBV EA-IgG titer and atherosclerosis was also evaluated by using logistic regression. RESULTS: Among rs3025039 CC-homozygotes, with the lowest EBV EA-IgG titer tertile as the reference, the multivariable odds ratio (95% confidence interval) was 1.11 (0.82, 1.50) for the medium tertile and 1.07 (0.78, 1.47) for the high tertile. Among rs3025039 (T) allele carriers, the corresponding values were 1.44 (0.88, 2.36) and 1.88 (1.15, 3.05), respectively. There was a significant interaction between rs3025039 (T) allele carrier status and the association between EBV EA-IgG titer and atherosclerosis (adjusted p = 0.0497). CONCLUSION EBV EA-IgG titer was significantly positively associated with atherosclerosis only among participants who are genetically less likely to have progressive angiogenesis. An angiogenesis-related genetic factor was revealed as a determinant of the association between EBV EA-IgG titer and atherosclerosis. These findings introduce a novel concept that could explain the association between viral infection and atherosclerosis.
Humans ; Aged ; Male ; Middle Aged ; Female ; Japan/epidemiology* ; Atherosclerosis/virology* ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/genetics* ; Epstein-Barr Virus Infections/virology* ; Polymorphism, Single Nucleotide ; Cross-Sectional Studies ; Herpesvirus 4, Human ; Antigens, Viral/immunology* ; Antibodies, Viral/blood* ; Immunoglobulin G/blood* ; Genotype ; East Asian People

Objective:To investigate the clinical characteristics and major allergens of patients with pollen-food allergy syndrome（PFAS） and their correlation with the severity of symptoms, and to provide a basis for identifying high-risk patients, optimizing the allergen testing process and developing individualized dietary management strategies. Methods:The clinical data of 166 patients with PFAS admitted to our hospital from January 2021 to July 2023 were retrospectively analyzed. The clinical symptoms, pollen types and food allergy of the patients were analyzed by questionnaire survey and serum specific IgE detection. phi coefficient, Apriori algorithm modeling and multivariate logistic regression analysis were used to evaluate the association between allergen and symptom severity. Results:Artemisia pollen was the most common allergen in this area, with a positive rate of 96.39%. Peach and mango were the most common food allergens, which caused allergic reactions in 24.10% and 22.89% of patients, respectively. Oral mucosal symptoms were the main symptoms. Correlation analysis showed that there was a correlation between pollen allergens and allergenic food. Association rule analysis showed that when the patient was allergic to the combination of peanuts and trees, the probability of high severity of symptoms was 82.35%. Multivariate analysis showed that ragweed allergy was significantly positively correlated with the severity of PFAS symptoms. Conclusion:Artemisia pollen and related food allergens play an important role in the pathogenesis of PFAS. Association rule mining and network map analysis revealed direct associations between peanut and tree combination allergy and symptom severity, as well as potential links between other inhaled allergens and specific food allergies. Ragweed and peach allergy are independent risk factors for the aggravation of PFAS symptoms, which can be used as early warning indicators. These results help to improve the screening of high-risk patients and the construction of regional allergen databases.
Humans ; Food Hypersensitivity/immunology* ; Allergens/immunology* ; Retrospective Studies ; Pollen/immunology* ; Cross Reactions ; Immunoglobulin E/blood* ; Rhinitis, Allergic, Seasonal/immunology* ; Artemisia/immunology* ; Male ; Female ; Adult ; Prunus persica/immunology* ; Arachis/immunology* ; Middle Aged ; Surveys and Questionnaires ; Oral Allergy Syndrome

OBJECTIVE: To observe the clinical efficacy of combination therapy of wheat-grained sized cone moxibustion and point-to-point needle insertion with medical ozone penetrating injection for allergic rhinitis (AR) and its effect on inflammation-related indexes. METHODS: Thirty-one patients with persistent AR were enrolled. The patients received medical ozone injection at bilateral Yingxiang (LI20)-to-Shangyingxiang (EX-HN8), and wheat-grained sized cone moxibustion at Dazhui (GV14), twice a week (with a 3-day interval) for 4 consecutive weeks. The total nasal symptoms score (TNSS), total non-nasal symptom score (TNNSS), rhinoconjunctivitis quality of life questionnaire (RQLQ), and rhinitis control assessment test (RCAT) scores were evaluated before treatment, after treatment, and at the 8-week follow-up. Levels of eosinophil (EOS) count, immunoglobulin E (IgE), interleukin (IL)-4, IL-6, and IL-17 were measured before and after treatment. Clinical efficacy was evaluated after treatment, and the recurrence rate was assessed at follow-up. RESULTS: Compared with those before treatment, the TNSS, TNNSS, and RQLQ scores were decreased (P<0.05), while the RCAT score was increased (P<0.05) after treatment and at follow-up. There were no statistically significant differences in above indexes between the post-treatment and follow-up (P>0.05). After treatment, the whole blood EOS count and serum levels of IgE, IL-4, IL-6, and IL-17 were decreased compared with those before treatment (P<0.05). After treatment, 17 cases were markedly effective, 12 cases were effective, and 2 cases were ineffective, resulting in a total effective rate of 93.5%. At follow-up, 2 cases relapsed, and the recurrence rate was 6.9%. CONCLUSION Combination therapy of wheat-grained sized cone moxibustion and point-to-point needle insertion with medical ozone injection can improve AR symptoms, reduce the recurrence rate, and enhance the quality of life. The mechanism may be associated with the regulation of immune-related indexes.
Humans ; Female ; Male ; Moxibustion ; Adult ; Ozone/administration & dosage* ; Middle Aged ; Young Adult ; Acupuncture Points ; Adolescent ; Combined Modality Therapy ; Treatment Outcome ; Immunoglobulin E/blood* ; Rhinitis, Allergic/immunology* ; Interleukin-4/immunology*