Human ; Male ; Child: 6-12 Yrs Old ; Linear Iga Bullous Dermatosis ; Immunoglobulin A ; Skin Diseases

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*

Research on IgG4-related disease (IgG4-RD), an autoimmune condition recognized to be a unique disease entity only two decades ago, has processed from describing patients' symptoms and signs to summarizing its critical pathological features, and further to investigating key pathogenic mechanisms. Challenges in gaining a better understanding of the disease, however, stem from its relative rarity-potentially attributed to underrecognition-and the absence of ideal experimental animal models. Recently, with the development of various high-throughput techniques, "omics" studies at different levels (particularly the single-cell omics) have shown promise in providing detailed molecular features of IgG4-RD. While, the application of omics approaches in IgG4-RD is still at an early stage. In this paper, we review the current progress of omics research in IgG4-RD and discuss the value of machine learning methods in analyzing the data with high dimensionality.
Humans ; Immunoglobulin G4-Related Disease/metabolism* ; Immunoglobulin G/metabolism* ; Machine Learning ; Animals ; Proteomics/methods*

OBJECTIVE: To investigate the effectiveness of tibial transverse transport (TTT) in treating Wagner grade 3-4 type 2 diabetic foot ulcers and analyze dynamic changes in immunoglobulin levels. METHODS: The clinical data of 68 patients with Wagner grade 3-4 type 2 diabetic foot ulcers treated with TTT between May 2022 and September 2023 was retrospectively analyzed. The cohort included 49 males and 19 females, aged 44-91 years (mean, 67.3 years), with 40 Wagner grade 3 and 28 grade 4 ulcers. The duration of type 2 diabetes ranged from 5 to 23 years, with an average of 10 years. The number of wound healing cases, healing time, amputation cases, death cases, and complications were observed and recorded. Serum samples were collected at 6 key time points [1 day before TTT and 3 days, 7 days (the first day of upward transverse transfer), 14 days (the first day of downward transverse transfer), 21 days (the first day after the end of transfer), 36 days (the first day after the removal of the transfer device)], and the serum immunoglobulin levels were detected by flow cytometry including immunoglobulin G (IgG), IgA, IgM, IgE, complement C3 (C3), C4, immunoglobulin light chain κ (KAP), immunoglobulin light chain λ (LAM). RESULTS: All the 68 patients were followed up 6 months. Postoperative pin tract infection occurred in 3 cases and incision infection in 2 cases. Amputation occurred in 5 patients (7.4%) at 59-103 days after operation, and 8 patients (11.8%) died at 49-77 days after operation; the wounds of the remaining 55 patients (80.9%) healed in 48-135 days, with an average of 80 days. There was no recurrence of ulcer, peri-osteotomy fracture, or local skin necrosis during follow-up. The serum immunoglobulin levels of 55 patients with wound healing showed that the levels of IgG and IgM decreased significantly on the 3rd and 7th day after operation compared with those before operation ( P<0.05), and gradually returned to the levels before operation after 14 days, and reached the peak on the 36th day. IgA levels continued to decrease with time, and there were significant differences at all time points when compared with those before operation ( P<0.05). The level of IgE significantly decreased at 21 days after operation compared with that before operation ( P<0.05), while it was higher at other time points than that before operation, but the difference was not significant ( P>0.05). The level of C3 showed a clear treatment-related increase, which was significantly higher on the 7th, 14th, and 21st days after operation than that before operation ( P<0.05), and the peak appeared on the 14th day. The change trend of C4 level was basically synchronous with that of C3, but the amplitude was smaller, and the difference was significant at 7 and 14 days after operation compared with that before operation ( P<0.05). There was no significant difference in KAP/LAM between different time points before and after operation ( P>0.05). CONCLUSION TTT can accelerate wound healing, effectively treat diabetic foot ulcer, and reduce amputation rate, and has definite effectiveness. The potential mechanisms of TTT in the treatment of diabetic foot ulcers include the dynamic regulation of IgG, IgA, IgM, and IgE levels to balance the process of inflammation and repair, and the periodic increase of C3 and C4 levels may promote tissue cleaning, angiogenesis, and anti-infection defense.
Humans ; Male ; Female ; Middle Aged ; Aged ; Diabetic Foot/immunology* ; Wound Healing ; Adult ; Retrospective Studies ; Aged, 80 and over ; Treatment Outcome ; Tibia/transplantation* ; Diabetes Mellitus, Type 2/complications* ; Amputation, Surgical ; Immunoglobulins/blood* ; Immunoglobulin G/blood*

Objective To construct a library of human-derived anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) single-chain variable fragments (scFv) and screen for broad-spectrum neutralizing antibodies to identify candidate molecules for the development of diagnostic and therapeutic agents. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from the peripheral blood of patients who had recovered from novel coronavirus infection. Total RNA was extracted from these PBMCs and reverse transcribed into cDNA, which was used as a template for constructing a human anti-SARS-CoV-2 scFv library. Phage display technology was used to screen for scFv antibodies specific to the SARS-CoV-2 S protein. Full-length IgG antibodies were synthesized through sequence analysis and human IgG expression, and their binding capacity and neutralizing activity against SARS-CoV-2 were evaluated. Results A human-derived scFv antibody library against SARS-CoV-2 with a capacity of 1.56×10⁷ CFU was successfully constructed. Two specific scFv antibodies were screened from this library and expressed as full-length IgG antibodies (IgG-A10 and IgG-G6). IgG-A10 exhibited strong neutralizing activity against both the original SARS-CoV-2 strain (WT) and the XBB subvariant of the Omicron variant. However, the neutralizing activity of this antibody against the JN.1 sub lineage of the Omicron BA.2.86 variant was moderate. Conclusion This study has successfully constructed a human anti-SARS-CoV-2 scFv antibody library from the peripheral blood of recovered patients, and screened and expressed anti-SARS-CoV-2 IgG antibodies with neutralizing activity, laying a foundation for the prevention, diagnosis, and treatment of SARS-CoV-2 infection.
Humans ; Single-Chain Antibodies/genetics* ; SARS-CoV-2/immunology* ; COVID-19/immunology* ; Immunoglobulin G/genetics* ; Antibodies, Viral/genetics* ; Peptide Library ; Spike Glycoprotein, Coronavirus/immunology* ; Antibodies, Neutralizing/immunology* ; Leukocytes, Mononuclear/immunology* ; Broadly Neutralizing Antibodies/immunology*

Objective To explore the effect of Evodiamine (Evo) on the immune function of allergic rhinitis (AR) rats and the regulatory mechanism on C-C motif chemokine ligand 2 (CCL2)/ C-C motif chemokine receptor 2 (CCR2) pathway. Methods The related targets of Evo-AR-immune function were screened by network pharmacology, and the protein interaction network diagram of intersecting targets was constructed. The AR rat model was established by ovalbumin (OVA) combined with aluminium hydroxide, and the rats were divided into six groups: a normal control (NC) group, a model group, a Loratadine (LOR) group, an Evodiamine low dose (Evo-L) group, a Evodiamine high dose (Evo-H) groups, and an Evo-H combined with CCL2 group. After the last administration, the symptoms of rats in each group were scored; ELISA was applied to detect the levels of histamine, immunoglobulin E (IgE), interleukin 4 (IL-4), IL-13 and interferon γ (IFN-γ); Diff-Quick staining solution was applied to detecte the number of cells in the nasal lavage fluid (NALF); hematoxylin eosin (HE) staining was applied to observe the pathological changes of nasal mucosa tissue; real-time quantitative PCR was applied to detect the levels of CCL2 and CCR2 mRNA in tissue; Western blot was applied to detect the expression levels of CCL2, CCR2 and CXC motif chemokine ligand 8 (CXCL8) proteins in nasal mucosa. Results There were eight intersection targets of EVo-AR-immune function, and protein interaction network diagram showed that CXCL8 was the core target. Compared with the NC group, the score of nasal symptoms, the levels of histamine, IgE, IL-4 and IL-13, the numbers of eosinophil, macrophages, neutrophils, lymphocytes and total cells, the mRNA and protein expression levels of CCL2 and CCR2, and the expression of CXCL8 protein in the model group were increased, while the level of IFN-γ was decreased. Compared with the model group, the score of nasal symptoms, the levels of histamine, IgE, IL-4 and IL-13, the numbers of eosinophil, macrophages, neutrophils, lymphocytes and total cells, the mRNA and protein expression levels of CCL2 and CCR2, and the expression of CXCL8 protein in LOR and Evo groups were decreased, while the level of IFN-γ was increased. Further use of CCL2 recombinant protein for compensatory experiments revealed that the improvement effect of Evo on immune function in AR rats was reversed by CCL2. Conclusion Evo can improve the immune function of AR rats, and its mechanism may be related to the inhibition of the CCL2/CCR2 pathway.
Animals ; Receptors, CCR2/immunology* ; Signal Transduction/drug effects* ; Chemokine CCL2/immunology* ; Rats ; Rhinitis, Allergic/metabolism* ; Immunoglobulin E/blood* ; Quinazolines/pharmacology* ; Male ; Interferon-gamma ; Rats, Sprague-Dawley ; Interleukin-13 ; Histamine ; Interleukin-4/immunology* ; Disease Models, Animal

Objective To explore the effects of S100 calcium-binding protein A9 (S100A9) gene knockout on the phenotype of systemic lupus erythematosus (SLE) in mice and to clarify the role of S100A9 in the pathogenesis of SLE. Methods Ten female C57BL/6 wild-type and S100A9 knockout (S100A9-KO ) mice were selected, with five wild-type and five S100A9-KO B6 mice receiving imiquimod (IMQ) cream to establish SLE mouse model. The other five wild-type and five S100A9-KO B6 mice were treated as control groups by wiping the skin of the right ear with a cotton swab. After 8 weeks, the mice were sacrificed. The serum was collected from each mouse to detect the levels of anti-double-stranded DNA (dsDNA) antibodies, immunoglobulin G (IgG), B cell activating factor (BAFF), and interleukin 6 (IL-6) using ELISA. The levels of serum creatinine were determined using a sarcosine oxidase method. Urine was collected to measure urinary protein concentration. Kidneys were collected and stained with hematoxylin and eosin (H&E) for evaluating histological changes. Results After IMQ treatment, the length and weight of spleen, levels of serum creatinine, anti-dsDNA antibodies, IgG, BAFF, IL-6, and urinary protein in the IMQ B6 group and IMQ S100A9-KO B6 group were significantly higher than those of the control groups. Lupus-like changes including increased glomerular volume and tubular epithelial swelling were observed in kidneys from the IMQ and IMQ S100A9-KO groups. However, compared with the IMQ B6 group, the IMQ S100A9-KO B6 group exhibited milder levels of serum and urine indicators as well as the lupus-like symptoms. Conclusion IMQ could induce lupus-like symptoms in both wild-type B6 mice and S100A9-KO B6 mice, but the lesions in S100A9 knockout mice are milder. Theses results suggested that S100A9 is involved in and promotes the pathogenesis of SLE.
Animals ; Lupus Erythematosus, Systemic/chemically induced* ; Female ; Calgranulin B/genetics* ; Mice, Knockout ; Mice, Inbred C57BL ; Phenotype ; Mice ; Interleukin-6/blood* ; Disease Models, Animal ; Antibodies, Antinuclear/blood* ; B-Cell Activating Factor/blood* ; Immunoglobulin G/blood* ; Kidney/pathology*

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*