[ ABSTRACT] AIM:To observe the inhibitory effect of madecassoside on the LPS-stimulated microglia and to inves-tigate its possible mechanism.METHODS:Microglia cells of neonatal Sprague-Dawley ( SD) rats were cultured, isolated and purified.Microglia cells were activated with lipopolysaccharide ( LPS) .The inhibitory effect of madecassoside on micro-glia was measured by MTT assay.Tumor necrosis factor alpha (TNF-α), interleukin 1β(IL-1β) were detected by ELISA. Cell cycle and apoptotic rate were evaluated by flow cytometry.The expression of TLR4 was detected by Western blotting. The expression of NF-κB was detected by RT-PCR.RESULTS: LPS induced the proliferation of microglia and release in-flammatory cytokines significantly.Compared with LPS group, madecassoside inhibited the proliferation of microglia induced by LPS in a dose dependent manner.The IC50 value of madecassoside was 10.97 nmol/L to microglia after incubation for 48 h.Madecassoside also decreased the levels of TNF-αand IL-6, increased the ratios of microglia at the G2 phase and the ap-optotic rate, decreased the expression of TLR4 and NF-κB significantly (P<0.05).CONCLUSION:Madecassoside has in-hibitory effects on the proliferation of LPS-stimulated microglia, by which the mechanism may be related to inhibition of the expression of TLR4 and NF-κB, change of cell cycle distribution and induction of microglia apoptosis.

Objective: To investigate the etiology, diagnosis and treatment principles of inherited permanent tooth embryo necrosis caused by alveolar bone resorption due to severe periapical periodontitis of deciduous teeth, in order to provide a reference for clinical diagnosis and treatment Methods: The clinical data and related literature of a rare case of permanent tooth embryo necrosis were analyzed retrospectively. Results : This case was a 5-year-old girl. Physical examination and X-ray examination revealed chronic periapical inflammation in 75. X-ray showed that the periodontal bone of tooth 75 was extensively destroyed; additionally, the permanent tooth germ of tooth 35 was incomplete and the development was delayed compared to that of tooth 45 because of severe periapical periodontitis in the primary teeth. The initial diagnosis was that-- the embryo of tooth 35 stopped developing due to inflammation and was necrotic after tooth 75 was extracted. The postoperative pathological examination report showed that most bone around the embryos of tooth 35 was sequestrated. Through literature review and analysis, it was found that the degree of periapical lesions in the primary teeth and the developmental stage of the tooth embryo have a great impact on the formation of permanent tooth embryos. Conservative methods such as root canal therapy are usually adopted as treatment. Permanent tooth embryo necrosis caused by periapical periodontitis of deciduous teeth is rare in the clinic, so it is necessary to judge the degree of inflammatory infiltration and of tooth embryo damage as soon as possible according to the clinical symptoms and imaging manifestations; and to make a correct treatment plan. Conclusion There are no objective and clear diagnostic and treatment criteria for the clinical diagnosis of the pathological state of permanent tooth embryo, thus, methods such as etiology elimination and follow-up observation are usually adopted for abnormal permanent tooth embryo development. Future research should focus on prevention and finding addtional effective methods for diagnosis and treatment.

Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.