Objective To investigate the effects and underlying mechanisms of Shexiang Baoxin pill(SBP)on wire injury-induced valvular dysfunction in rats.Methods A rat model of aortic valve injury was established using a standardized wire injury method.Animals were randomly divided into control,sham,model,and SBP low-,medium-,and high-dose(SBP-L,SBP-M,SBP-H)intervention groups.Aortic valve function was evaluated using echocardiography.Histopathological changes were assessed using hematoxylin-eosin(HE)and Masson's staining.Serum levels of lipid peroxides(LPO),malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH),and total iron were measured using biochemical assays.Expression levels of ferroptosis-related proteins(ACSL4,SLC7A11,and GPX4)and osteogenic markers(RUNX2 and BMP2)in valve tissues were detected through Western blot and RT-qPCR.Results The SBP-M and SBP-H groups showed significantly higher aortic valve orifice areas((3.70±0.04)mm2 and(3.90±0.11)mm2 vs(2.25±0.37)mm2,P＜0.0001),lower transvalvular pressure gradients((0.52±0.09)mmHg and(0.49±0.13)mmHg vs(0.90±0.17)mmHg,P＜0.01),and lower aortic valve peak flow velocities((68.83±4.98)cm/s and(63.61±11.43)cm/s vs(87.14±11.22)cm/s,P＜0.05,P＜0.01)than those in the model group.HE and Masson's staining result demonstrated that SBP alleviates valve thickening and fibrosis(fibrotic area:(35.98±5.2)5％vs(53.01±2.44)％,P＜0.01).Biochemical tests showed that SBP reduces serum levels of lipid peroxidation products(LPO and MDA)and total iron ions while increasing SOD and GSH levels(P＜0.001,P＜0.0001).SBP downregulated the ferroptosis-related protein ACSL4(P＜0.01),upregulated the anti-ferroptosis proteins SLC7A11 and GPX4(P＜0.05,P＜0.01),and inhibited the expression of the osteogenic molecules RUNX2 and BMP2(P＜0.05,P＜0.01,P＜0.0001).Conclusions SBP may alleviate mechanical injury-induced valve dysfunction in rats through the modulation of oxidative stress and restoration of iron homeostasis.These findings provide experimental evidence for the role of SBP in the early intervention of valvular disease.The precise active components,molecular targets,and clinical translation of SBP require further investigation.

Objective:To investigate the disease-modifying effect of long-course use of Omalizumab (OMZ) on children and adolescents with allergic asthma.Methods:Retrospective cohort study.The clinical data of 66 children with moderate to severe allergic asthma treated with OMZ in the Department of Pediatrics, the Second Hospital of Tianjin Medical University from April 2019 to June 2024 were analyzed.According to the course of OMZ, the patients were divided into a short course group (33 cases), a medium course group (21 cases), and a long course group (12 cases).The courses of treatment of the 3 groups were 6-<12, 12-<24 and 24 months or more, respectively.Pulmonary ventilation functions [including the percentage of forced expiratory volume in the first second to the expected value (FEV 1%pred), the peak expiratory flow rate to the expected value (PEF%pred), and the maximum mid-expiratory flow to the expected value (MMEF%pred)], fractional exhaled nitric oxide (FeNO) and the absolute value of peripheral blood eosinophils (EOS) were analyzed before and after OMZ treatment.Moreover, whether allergic asthma and comorbidities such as allergic rhinitis (AR), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU) were controlled was explored.Changes in inhaled corticosteroids (ICS) and serum total immunoglobulin E (TIgE) levels were measured.The paired t-test was used for testing measurement data with normal distribution, and the rank sum test for testing non-normally distributed data. Results:(1)Changes of pulmonary ventilation function, FeNO and EOS: the pulmonary ventilation function in the short course group, the FEV 1%pred and MMEF%pred in the medium course group, and the PEF%pred and MMEF%pred in the long course group were improved compared with those at baseline (all P<0.05).FeNO levels in all the 3 groups decreased, compared with those at baseline (all P<0.05).There was no significant difference in peripheral blood EOS between the 3 groups compared with those at baseline (all P>0.05).(2)Control status of allergic asthma and comorbidities: the Asthma Control Test/Childhood Asthma Control Test (ACT/C-ACT), Asthma Control Questionnaire (ACQ) scores and the visual analogue scores (VAS) of rhinitis improved in all 3 groups, compared with those at baseline (all P<0.05).Among 4 patients complicated with AD, 3(75.0%) showed decreased Scoring Atopic Dermatitis Index(SCORAD) scores, compared with those at baseline.Of the 6 children complicated with CSU, 5(83.3%) did not develop rash after injection.(3)Frequency of acute exacerbations of asthma: the number of acute exacerbations of asthma after treatment was lower than that before treatment in all the 3 groups (all P<0.05).The number of attacks in the long course group was decreased in the third year, compared with that in the first year ( P<0.05).(4)The ICS consumption: the ICS consumption in all the 3 groups was significantly decreased, compared with that at baseline (all P<0.05).Six patients (28.6%) in the medium course group had no recurrence within 1 year after stopping ICS therapy.One of the 7 patients (14.3%) in the long course group had stopped ICS for more than 2 years, and 3 patients (42.9%) had stopped ICS for more than 1 year.These 4 children had no recurrence.(5)The change of TIgE: in the short and medium course groups, serum TIgE levels at the end of treatment were higher than those at baseline (all P<0.05).The serum TIgE level in the second year of treatment was higher than that at baseline in the long course group ( P<0.05).The serum TIgE level in the third year of treatment was decreased, compared with that in the second year ( P<0.05). Conclusions:OMZ can improve lung function and FeNO levels, reduce the incidence of acute exacerbations of asthma, and lower ICS usage in children.At the same time, it can also improve the allergic diseases AR, AD and CSU.The prolonged treatment of OMZ can bring long-term sustained benefits to children.The changes in serum TIgE and FeNO levels may suggest that the long-term application of OMZ plays a disease-modifying role in allergic asthma.

Objective To investigate the effects and underlying mechanisms of Shexiang Baoxin pill(SBP)on wire injury-induced valvular dysfunction in rats.Methods A rat model of aortic valve injury was established using a standardized wire injury method.Animals were randomly divided into control,sham,model,and SBP low-,medium-,and high-dose(SBP-L,SBP-M,SBP-H)intervention groups.Aortic valve function was evaluated using echocardiography.Histopathological changes were assessed using hematoxylin-eosin(HE)and Masson's staining.Serum levels of lipid peroxides(LPO),malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH),and total iron were measured using biochemical assays.Expression levels of ferroptosis-related proteins(ACSL4,SLC7A11,and GPX4)and osteogenic markers(RUNX2 and BMP2)in valve tissues were detected through Western blot and RT-qPCR.Results The SBP-M and SBP-H groups showed significantly higher aortic valve orifice areas((3.70±0.04)mm2 and(3.90±0.11)mm2 vs(2.25±0.37)mm2,P＜0.0001),lower transvalvular pressure gradients((0.52±0.09)mmHg and(0.49±0.13)mmHg vs(0.90±0.17)mmHg,P＜0.01),and lower aortic valve peak flow velocities((68.83±4.98)cm/s and(63.61±11.43)cm/s vs(87.14±11.22)cm/s,P＜0.05,P＜0.01)than those in the model group.HE and Masson's staining result demonstrated that SBP alleviates valve thickening and fibrosis(fibrotic area:(35.98±5.2)5％vs(53.01±2.44)％,P＜0.01).Biochemical tests showed that SBP reduces serum levels of lipid peroxidation products(LPO and MDA)and total iron ions while increasing SOD and GSH levels(P＜0.001,P＜0.0001).SBP downregulated the ferroptosis-related protein ACSL4(P＜0.01),upregulated the anti-ferroptosis proteins SLC7A11 and GPX4(P＜0.05,P＜0.01),and inhibited the expression of the osteogenic molecules RUNX2 and BMP2(P＜0.05,P＜0.01,P＜0.0001).Conclusions SBP may alleviate mechanical injury-induced valve dysfunction in rats through the modulation of oxidative stress and restoration of iron homeostasis.These findings provide experimental evidence for the role of SBP in the early intervention of valvular disease.The precise active components,molecular targets,and clinical translation of SBP require further investigation.

Asthma is one of the most common chronic respiratory diseases.Inhaled corticosteroid（ICS）are the first line of asthma maintenance therapy.ICS maintenance therapy combined with short-acting beta-2 agonist（SABA）reliever therapy has been a common treatment in the past few decades.However，there are some problems such as poor patient compliance.In recent years，the Global Initiative for Asthma（GINA）has suggested that low-dose ICS-formoterol is preferred as a reliever therapy to help improve patient compliance and reduce the risk of exacerbation after an acute attack of asthma.This article summarizes the application value of ICS-formoterol in the treatment of asthma maintenance and reliever.

Objective:To investigate the disease-modifying effect of long-course use of Omalizumab (OMZ) on children and adolescents with allergic asthma.Methods:Retrospective cohort study.The clinical data of 66 children with moderate to severe allergic asthma treated with OMZ in the Department of Pediatrics, the Second Hospital of Tianjin Medical University from April 2019 to June 2024 were analyzed.According to the course of OMZ, the patients were divided into a short course group (33 cases), a medium course group (21 cases), and a long course group (12 cases).The courses of treatment of the 3 groups were 6-<12, 12-<24 and 24 months or more, respectively.Pulmonary ventilation functions [including the percentage of forced expiratory volume in the first second to the expected value (FEV 1%pred), the peak expiratory flow rate to the expected value (PEF%pred), and the maximum mid-expiratory flow to the expected value (MMEF%pred)], fractional exhaled nitric oxide (FeNO) and the absolute value of peripheral blood eosinophils (EOS) were analyzed before and after OMZ treatment.Moreover, whether allergic asthma and comorbidities such as allergic rhinitis (AR), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU) were controlled was explored.Changes in inhaled corticosteroids (ICS) and serum total immunoglobulin E (TIgE) levels were measured.The paired t-test was used for testing measurement data with normal distribution, and the rank sum test for testing non-normally distributed data. Results:(1)Changes of pulmonary ventilation function, FeNO and EOS: the pulmonary ventilation function in the short course group, the FEV 1%pred and MMEF%pred in the medium course group, and the PEF%pred and MMEF%pred in the long course group were improved compared with those at baseline (all P<0.05).FeNO levels in all the 3 groups decreased, compared with those at baseline (all P<0.05).There was no significant difference in peripheral blood EOS between the 3 groups compared with those at baseline (all P>0.05).(2)Control status of allergic asthma and comorbidities: the Asthma Control Test/Childhood Asthma Control Test (ACT/C-ACT), Asthma Control Questionnaire (ACQ) scores and the visual analogue scores (VAS) of rhinitis improved in all 3 groups, compared with those at baseline (all P<0.05).Among 4 patients complicated with AD, 3(75.0%) showed decreased Scoring Atopic Dermatitis Index(SCORAD) scores, compared with those at baseline.Of the 6 children complicated with CSU, 5(83.3%) did not develop rash after injection.(3)Frequency of acute exacerbations of asthma: the number of acute exacerbations of asthma after treatment was lower than that before treatment in all the 3 groups (all P<0.05).The number of attacks in the long course group was decreased in the third year, compared with that in the first year ( P<0.05).(4)The ICS consumption: the ICS consumption in all the 3 groups was significantly decreased, compared with that at baseline (all P<0.05).Six patients (28.6%) in the medium course group had no recurrence within 1 year after stopping ICS therapy.One of the 7 patients (14.3%) in the long course group had stopped ICS for more than 2 years, and 3 patients (42.9%) had stopped ICS for more than 1 year.These 4 children had no recurrence.(5)The change of TIgE: in the short and medium course groups, serum TIgE levels at the end of treatment were higher than those at baseline (all P<0.05).The serum TIgE level in the second year of treatment was higher than that at baseline in the long course group ( P<0.05).The serum TIgE level in the third year of treatment was decreased, compared with that in the second year ( P<0.05). Conclusions:OMZ can improve lung function and FeNO levels, reduce the incidence of acute exacerbations of asthma, and lower ICS usage in children.At the same time, it can also improve the allergic diseases AR, AD and CSU.The prolonged treatment of OMZ can bring long-term sustained benefits to children.The changes in serum TIgE and FeNO levels may suggest that the long-term application of OMZ plays a disease-modifying role in allergic asthma.

To investigate the short-term effectiveness and safety of sublingual allergen immunotherapy with allergen sprays (SLIT-sprays) in Chinese patients with allergic rhinitis (AR) with or without asthma using real-world data. The retrospective cohort study included 100 patients who received SLIT-sprays in the ENT departments in Hainan Shulan (Boao) Hospital and Boao Super Hospital between October 2023 and August 2024. A questionnaire survey was conducted to collect clinical data on the effectiveness and safety of SLIT-sprays, examining the types and incidence of adverse events (AEs) during treatment, treatments after the occurrence of AEs, and changes in Visual Analog Scale (VAS) scores before and after SLIT-sprays. Self-reports from 100 patients were collected. The results showed that the average treatment duration for the 100 patients was (90.7±58.9) days, median 78.5 days. Using changes in VAS scores as the effectiveness assessment, the average VAS score increased by 4.2 (95% CI: 4.06-4.34). The incidence of AEs during the SLIT-sprays was 17.0% (17/100), all of which were mild to moderate local reactions, with no serious AEs reported. There were no significant differences in AE incidence among patients with different diseases (AR or AR with asthma and asthma alone) (χ 2=1.831, P>0.05), different age group (χ 2=1.477, P>0.05), different types of allergen extracts (χ 2=1.613, P>0.05), or the number of allergen extracts used (patients using one or two allergen extracts) (Fisher′s exact test, P>0.05). In conclusion, Chinese patients showed good safety and tolerability to SLIT-sprays, with all AEs being mild to moderate local reactions and no serious or systemic AEs occurring. Patients reported positive subjective evaluations of the early treatment effects.

Objective To analyze the clinical characteristics of stiff left atrial syndrome (SLAS) after Mei mini maze procedure for atrial fibrillation (AF), and to explore its risk factors and treatments. Methods We retrospectively analyzed the clinical data of the patients who underwent Mei mini maze procedure in Xinhua Hospital between 2010 and 2020. According to whether SLAS occurred in the early postoperative period, patients were divided into a SLAS group and a non-SLAS group. The basic data, perioperative echocardiogram and laboratory test indexes of the two groups were compared. Results A total of 1 056 patients were collected. There were 672 (63.6%) males with an average age of 63.6±9.3 years, including 489 patients with persistent AF and 567 patients with paroxysmal AF. Fourteen (14/1 056, 1.3%) patients developed SLAS, with an average occurrence time of 2.1±1.1 days after the surgery. The average follow-up time of the whole group was 21.4±7.8 months. Two patients in the SLAS group developed SLAS again after discharge, and the occurrence time was 3 weeks and 4 weeks after the operation, respectively; while no SLAS occurred after discharge in the non-SLAS group. Diabetes and small preoperative left atrial diameter were risk factors for SLAS after surgery. Patients with SLAS had a good prognosis after adequate diuretic therapy. Conclusion The incidence of SLAS after Mei mini maze procedure for AF is low, and it mostly occurs in the early postoperative period. After adequate diuretic treatment, the prognosis is good.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.