Objective To investigate the role of Staphylococcus aureus enterotoxin B (SEB) in non-IgE mediated activation of mast cells (MCs) by in vitro co-culture of laboratory of allergic disease 2 (LAD2) cells and SEB.Methods The LAD2 cells were incubated with SEB at different concentrations of 0.01,0.1,1,10 and 100 μg/ml,A23187 positive control and negative control separately for 30 minutes.Then,effects of SEB on the morphology of MCs were observed by using a light microscope,and culture supernatants of the above incubation systems were collected.The concentration of tryptase released from MCs was analyzed by enzymatic activity assay,and the level of histamine was detected by enzyme-linked immunosorbent assay (ELISA).Results After 30-minute co-culture of LAD2 cells and SEB,MCs showed larger size,obscure boundaries,increased number of protuberances on the cell surface and decreased refractivity,with a radial burr fin-like appearance.After 30-minute co-culture of LAD2 cells and SEB at different concentrations of 0.01,0.1,1,10 and 100 μg/ml,the concentrations of tryptase in the culture supematants were 4.116 ± 0.651,5.344 ± 0.874,3.806 ± 0.459,1.309 ± 0.247,0.310 ± 0.199 ng/ml respectively.Additionally,the tryptase levels were significantly higher in the 0.01-,0.1-,1-μg/ml SEB groups than in the negative control group(1.538 ± 0.490,all P ＜ 0.05),and gradually decreased along with the increase of SEB concentrations.The histamine levels in the 0.01-,0.1-,1-,10-and 100-μg/ml SEB groups were 242.409 ± 63.915,522.491 ± 73.466,550.926 ± 84.466,334.397 ± 33.640,226.527 ± 5.678 ng/ml respectively.In the 0.01-,0.1-,1-μg/ml SEB groups,the levels of histamine released from MCs were gradually increased along with the increase of SEB concentrations,and were significantly higher than those in the negative control group (146.436 ± 3.100,all P ＜ 0.05).However,with the continued increase of SEB concentrations,the histamine levels gradually decreased.Conclusion SEB can directly activate MCs by a non-IgE mediated mechanism,followed by morphologic changes of MCs and release of tryptase and histamine.

Chronic spontaneous urticaria (CSU) is characterized by recurrent wheals with severe itching, and greatly affects the life quality of patients. The European guideline on chronic urticaria recommends the anti-IgE monoclonal antibody omalizumab as the only third-line therapy for patients with CSU whose condition can not be controlled by high doses of antihistamines. Although a lot of researches have shown that omalizumab is effective and safe for the treatment of CSU, its therapeutic mechanisms have not yet been fully elucidated. This review summarizes therapeutic mechanisms of omalizumab in the treatment of CSU, and indices for predicting and monitoring its clinical efficacy.

Objective:To investigate the efficacy and safety evaluation of omalizumab in patients with chronic urticaria who are not well treated with antihistamine and have a history of anaphylactic shock.Methods:A retrospective observational real-world study was conducted in which patients with chronic urticaria who were admitted to Peking University First Hospital from November 2018 to January 2024 who were poorly treated with antihistamine drugs and had a history of anaphylactic shock were selected as the study subjects, and 300 mg of omalizumab was injected subcutaneously every 4 weeks, and the occurrence of UCT (urticaria control test), the number of occurrences of anaphylactic shock and other adverse events were recorded during the treatment.Results:Among the 11 patients who started omalizumab treatment for 3 months, 10 patients had complete control of chronic urticaria (UCT=16), 1 patient was partially controlled (UCT=15), and 9 patients did not have anaphylactic shock during follow-up (10 cases after 12 months of follow-up and 1 case after 2 months of follow-up). Two patients developed anaphylactic shock after omalizumab injection. In this study, during the follow-up period (2-38 months), 11 patients were well tolerated with omalizumab, of which 4 continued to use omalizumab for urticaria, 6 stopped using omalizumab due to good urticaria control and no recurrence of anaphylactic shock, and 1 was lost to follow-up.Conclusion:Omalizumab may have good efficacy and safety in patients with chronic urticaria who are poorly treated with antihistamines and have a history of anaphylactic shock, and may have a potential role in preventing anaphylactic shock.

The neuroimmune mechanism of rosacea has not been fully elucidated, and it is believed that the innate immune system, immune cells, immune regulation, neuroimmune system, signaling pathway abnormalities and microbial dysbiosis are involved in the progress of the neuroimmune mechanism of rosacea. This article reviews the neuroimmune mechanism of rosacea.

Objective:To investigate the efficacy and safety evaluation of omalizumab in patients with chronic urticaria who are not well treated with antihistamine and have a history of anaphylactic shock.Methods:A retrospective observational real-world study was conducted in which patients with chronic urticaria who were admitted to Peking University First Hospital from November 2018 to January 2024 who were poorly treated with antihistamine drugs and had a history of anaphylactic shock were selected as the study subjects, and 300 mg of omalizumab was injected subcutaneously every 4 weeks, and the occurrence of UCT (urticaria control test), the number of occurrences of anaphylactic shock and other adverse events were recorded during the treatment.Results:Among the 11 patients who started omalizumab treatment for 3 months, 10 patients had complete control of chronic urticaria (UCT=16), 1 patient was partially controlled (UCT=15), and 9 patients did not have anaphylactic shock during follow-up (10 cases after 12 months of follow-up and 1 case after 2 months of follow-up). Two patients developed anaphylactic shock after omalizumab injection. In this study, during the follow-up period (2-38 months), 11 patients were well tolerated with omalizumab, of which 4 continued to use omalizumab for urticaria, 6 stopped using omalizumab due to good urticaria control and no recurrence of anaphylactic shock, and 1 was lost to follow-up.Conclusion:Omalizumab may have good efficacy and safety in patients with chronic urticaria who are poorly treated with antihistamines and have a history of anaphylactic shock, and may have a potential role in preventing anaphylactic shock.

The neuroimmune mechanism of rosacea has not been fully elucidated, and it is believed that the innate immune system, immune cells, immune regulation, neuroimmune system, signaling pathway abnormalities and microbial dysbiosis are involved in the progress of the neuroimmune mechanism of rosacea. This article reviews the neuroimmune mechanism of rosacea.

Objective:To investigate the pathogenesis and clinical manifestations of anaphylactic shock and to evaluate the effectiveness of existing treatments, so as to improve the understanding of anaphylactic shock and to properly manage patients with anaphylactic shock.Methods:A retrospective observational study was conducted to select 63 patients with anaphylactic shock who were diagnosed and treated in Peking University First Hospital from July 2017 to June 2023 as the study objects, and the clinical data including basic information, present medical history, vital signs, past medical history, emergency treatment measures and prognosis were collected, and the causes, clinical manifestations and emergency treatment measures of anaphylactic shock were descriptively analyzed.Results:The causes of anaphylactic shock in 63 subjects could be divided into drug allergy (50.79%), food allergy (15.87%), blood product allergy (11.11%), others (3.17%), radiotherapy (1.59%), strenuous exercise (1.59%), hemodialysis (1.59%), and the triggers in 9 cases (14.29%) were unclear. The clinical manifestations can be abnormalities of the skin, respiratory system, cardiovascular system, gastrointestinal system and urinary system, among which the most common skin manifestations are wheal rash, itching, redness and swelling (79.37%), the most common manifestation of the respiratory system is dyspnea (30.16%), and the highest proportion of cardiovascular manifestations is blood pressure lower than 90 mmHg or baseline blood pressure drop of 30 mmHg (100.00%). The most commonly used therapeutic drugs were epinephrine (49.2%), glucocorticoids (69.8%), antihistamines (52.4%), vasopressors (12.7%), and others.Conclusion:The causes of anaphylactic shock are different, and the clinical manifestations are complex and diverse, and the condition can be severe and life-threatening. Clinically, attention should be paid to the early and accurate identification of high-risk patients, the prevention of anaphylactic shock, and the timely taking of corresponding measures to protect the life safety of patients once anaphylactic shock occurs. Early diagnosis and prompt treatment are key to managing anaphylactic shock.

Objective:To investigate the pathogenesis and clinical manifestations of anaphylactic shock and to evaluate the effectiveness of existing treatments, so as to improve the understanding of anaphylactic shock and to properly manage patients with anaphylactic shock.Methods:A retrospective observational study was conducted to select 63 patients with anaphylactic shock who were diagnosed and treated in Peking University First Hospital from July 2017 to June 2023 as the study objects, and the clinical data including basic information, present medical history, vital signs, past medical history, emergency treatment measures and prognosis were collected, and the causes, clinical manifestations and emergency treatment measures of anaphylactic shock were descriptively analyzed.Results:The causes of anaphylactic shock in 63 subjects could be divided into drug allergy (50.79%), food allergy (15.87%), blood product allergy (11.11%), others (3.17%), radiotherapy (1.59%), strenuous exercise (1.59%), hemodialysis (1.59%), and the triggers in 9 cases (14.29%) were unclear. The clinical manifestations can be abnormalities of the skin, respiratory system, cardiovascular system, gastrointestinal system and urinary system, among which the most common skin manifestations are wheal rash, itching, redness and swelling (79.37%), the most common manifestation of the respiratory system is dyspnea (30.16%), and the highest proportion of cardiovascular manifestations is blood pressure lower than 90 mmHg or baseline blood pressure drop of 30 mmHg (100.00%). The most commonly used therapeutic drugs were epinephrine (49.2%), glucocorticoids (69.8%), antihistamines (52.4%), vasopressors (12.7%), and others.Conclusion:The causes of anaphylactic shock are different, and the clinical manifestations are complex and diverse, and the condition can be severe and life-threatening. Clinically, attention should be paid to the early and accurate identification of high-risk patients, the prevention of anaphylactic shock, and the timely taking of corresponding measures to protect the life safety of patients once anaphylactic shock occurs. Early diagnosis and prompt treatment are key to managing anaphylactic shock.

Objective To investigate the role of mast cells in Staphylococcus aureus enterotoxin B (SEB)-induced atopic dermatitis (AD)-like skin inflammation in BALB/c mice.Methods A total of 24 BALB/c mice were randomly and equally divided into 4 groups to be topically treated with ovalbumin (OVA group),SEB (SEB group),OVA + SEB (OVA + SEB group) and sodium chloride physiological solution (control group) respectively,so as to establish mouse models of epicutaneously induced AD-like skin inflammation.The AD-like skin lesions were evaluated by clinical observation and eczema area and severity index (EASI).Biopsy specimens were obtained from lesional skin of mice and then subjected to toluidine blue staining and immunohistochemical staining to count the mast cells,observe the morphology and distribution of mast cells,and calculate the percentage of degranulated mast cells.Results After 7-week treatment,the OVA group,SEB group and OVA + SEB group all showed severer local skin inflammation,higher EASI scores and denser infiltration of inflammatory cells compared with the control group.Moreover,the OVA + SEB group showed significantly severer local skin inflammation,skin lesions and degree of infiltration of inflammatory cells compared with the OVA group and SEB group (all P ＜ 0.05).The number of mast cells in the dermis of AD-like skin lesions per high-power field (× 400) was significantly higher in the OVA group (median [quartile range]:10.625 [3.675]),SEB group (11.000 [4.163]) and OVA + SEB group (13.875 [8.813]) than that in the control group (5.925 [2.088],all P ＜ 0.05).The SEB group (71.083％ ± 14.519％) and OVA + SEB group (58.767％ ±.16.978％) both showed significantly higher percentage of degranulated mast cells compared with the OVA group (24.050％ ± 11.161％,both P ＜ 0.05) and control group (23.617％ ± 8.132％,both P ＜ 0.05).Bivariate correlation analysis showed that the number of mast cells in the skin lesions was positively linearly correlated with the EASI scores (P ＜ 0.05).Conclusions Epicutaneous application of SEB can induce AD-like skin lesions in mice,and can exacerbate the severity of OVA-induced AD-like skin lesions.Mast cell proliferation,activation/degranulation and tryptase release may participate in the inflammation.

Objective To compare the efficacy and safety of the long-term intermittent maintenance treatment with tacrolimus 0.03％ ointment versus traditional treatment in reducing relapses and prolonging the recurrence interval in children with moderate to severe atopic dermatitis (AD).Methods A two-phase randomized,open-labelled,controlled clinical trial was conducted from September 2012 to November 2013.In the first phase,a total of 171 children aged 2-15 years with moderate to severe AD were enrolled from 7 hospitals in China,and received conventional treatment with tacrolimus 0.03％ ointment twice a day for 2-6 weeks.At the end of the treatment,the patients who achieved an investigator's global assessment (IGA) score ≤ 2 (n =125) were randomly classified into 2 groups to receive the second-phase treatment:test group (n =62) receiving intermittent maintenance treatment with tacrolimus 0.03％ ointment twice a week (Monday and Thursday),and control group (n =63) receiving no treatment.If the patients in the 2 groups experienced relapse,they received conventional treatment with tacrolimus 0.03％ ointment twice a day.The overall observation period was 6 months.The primary endpoint was the time to the first relapse,which was defined as the number of days from the end of the first-phase treatment to the first relapse.The secondary endpoints included the number of relapses at the second-phase trial,the disease severity at the time of relapse,the duration of relapse,the pruritus score at the time of relapse,the total amount of tacrolimus ointment used,the total response rate at the second-phase trial,and the incidence of adverse events.Results A total of 125 children with AD were enrolled into the second-phase trial,and 121 of them completed the follow-up.Among the 121 patients,the recurrence rate was significantly lower in the test group (25/60,41.7％) than in the control group (46/61,75.4％;x2 =14.20,P ＜ 0.001).The time to the first relapse was significantly longer in the test group (46.9 ± 37.7 d) than in the control group (28.8 ± 32.3 d;Z =1 093.50,P =0.020).The total number of recurrence was 31 and 86 in the test group and control group respectively,and the mean number of recurrence in each patient was significantly lower in the test group (0.52 ± 0.68) than in the control group (1.41 ± 1.23,t =4.96,P ＜ 0.001).There were no significant differences between the two groups regarding disease severity during relapse (eczema area and severity index:Z =971.50,P =0.39),duration of relapse (Z =747.00,P =0.07),and pruritus score during relapse (Z =894.00,P =0.95).The therapeutic drug was tolerated well in all the children,and no tacrolimus-related serious adverse events occurred.Conclusion The intermittent maintenance treatment with tacrolimus 0.03％ ointment twice a week for 6 months can effectively and safely prevent and reduce relapses,and prolong the recurrence interval in children with moderate to severe AD.