Pub Date : 2024-05-09eCollection Date: 2024-01-01DOI: 10.2147/JAA.S447093
Sanna Toppila-Salmi, Leif Bjermer, Lars-Olaf Cardell, Anders Cervin, Tuuli Heinikari, Lauri Lehtimäki, Marie Lundberg, Jens C Richter, Saara Sillanpää
Severe chronic rhinosinusitis with nasal polyposis (CRSwNP) is a disabling airway disease that significantly impacts patients' lives through the severity of symptoms, the need for long-term medical treatment and the high risk of recurrence post-surgery. Biological agents targeting type 2 immune responses underlying the pathogenesis of CRSwNP have shown effectiveness in reducing polyp size and eosinophilic infiltrate, and in decreasing the need for additional sinus surgeries. However, despite recent progress in understanding and treating the disease, type 2 inflammation-driven severe CRSwNP continues to pose challenges to clinical management due to several factors such as persistent inflammation, polyp recurrence, heterogeneity of disease, and comorbidities. This article presents the findings of a scientific discussion involving a panel of ear, nose and throat (ENT) specialists and pulmonologists across Sweden and Finland. The discussion aimed to explore current management practices for type 2 inflammation-driven severe CRSwNP in the Nordic region. The main topics examined encompassed screening and referral, measurements of disease control, treatment goals, and future perspectives. The experts emphasized the importance of a collaborative approach in the management of this challenging patient population. The discussion also revealed a need to broaden treatment options for patients with type 2 inflammation-driven CRSwNP and comorbid conditions with shared type 2 pathophysiology. In light of the supporting evidence, a shift in the disease model from the presence of polyps to that of type 2 inflammation may be warranted. Overall, this discussion provides valuable insights for the scientific community and can potentially guide the future management of CRSwNP.
{"title":"Multi-Disciplinary Expert Perspective on the Management of Type 2 Inflammation-Driven Severe CRSwNP: A Brief Overview of Pathophysiology and Recent Clinical Insights.","authors":"Sanna Toppila-Salmi, Leif Bjermer, Lars-Olaf Cardell, Anders Cervin, Tuuli Heinikari, Lauri Lehtimäki, Marie Lundberg, Jens C Richter, Saara Sillanpää","doi":"10.2147/JAA.S447093","DOIUrl":"10.2147/JAA.S447093","url":null,"abstract":"<p><p>Severe chronic rhinosinusitis with nasal polyposis (CRSwNP) is a disabling airway disease that significantly impacts patients' lives through the severity of symptoms, the need for long-term medical treatment and the high risk of recurrence post-surgery. Biological agents targeting type 2 immune responses underlying the pathogenesis of CRSwNP have shown effectiveness in reducing polyp size and eosinophilic infiltrate, and in decreasing the need for additional sinus surgeries. However, despite recent progress in understanding and treating the disease, type 2 inflammation-driven severe CRSwNP continues to pose challenges to clinical management due to several factors such as persistent inflammation, polyp recurrence, heterogeneity of disease, and comorbidities. This article presents the findings of a scientific discussion involving a panel of ear, nose and throat (ENT) specialists and pulmonologists across Sweden and Finland. The discussion aimed to explore current management practices for type 2 inflammation-driven severe CRSwNP in the Nordic region. The main topics examined encompassed screening and referral, measurements of disease control, treatment goals, and future perspectives. The experts emphasized the importance of a collaborative approach in the management of this challenging patient population. The discussion also revealed a need to broaden treatment options for patients with type 2 inflammation-driven CRSwNP and comorbid conditions with shared type 2 pathophysiology. In light of the supporting evidence, a shift in the disease model from the presence of polyps to that of type 2 inflammation may be warranted. Overall, this discussion provides valuable insights for the scientific community and can potentially guide the future management of CRSwNP.</p>","PeriodicalId":15079,"journal":{"name":"Journal of Asthma and Allergy","volume":"17 ","pages":"431-439"},"PeriodicalIF":3.2,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Prediction of asthma in preschool children is challenging and lacks objective indicators. The aim is to observe and analyze the variances between impulse oscillometry (IOS) and fractional expiratory nitric oxide (FeNO) in preschool children with wheezing, establish a joint prediction model, and explore the diagnostic value of combining IOS with FeNO in diagnosing asthma among preschool children.
Patients and methods: This study enrolled children aged 3-6 years with wheezing between June 2021 and June 2022. They were categorized as asthmatic (n=104) or non-asthmatic (n=109) after a 1-year follow-up. Clinical data, along with IOS and FeNO measurements from both groups, underwent univariate regression and multiple regression analyses to identify predictive factors and develop the most accurate model. The prediction model was built using the stepwise (stepAIC) method. The receiver operating characteristic curve (ROC), calibration curve, Hosmer-Lemeshow test, and decision curve analysis (DCA) were employed to validate and assess the model.
Results: During univariate analysis, a history of allergic rhinitis, a history of eczema or atopic dermatitis, and measures including FeNO, R5, X5, R20, Fres, and R5-R20 were found to be associated with asthma diagnosis. Subsequent multivariate analysis revealed elevated FeNO, R5, and X5 as independent risk factors. The stepAIC method selected five factors (history of allergic rhinitis, history of eczema or atopic dermatitis, FeNO, R5, X5) and established a prediction model. The combined model achieved an AUROC of 0.94, with a sensitivity of 0.89 and specificity of 0.88, surpassing that of individual factors. Calibration plots and the HL test confirmed satisfactory accuracy.
Conclusion: This study has developed a prediction model based on five factors, potentially aiding clinicians in early identification of asthma risk among preschool children.
{"title":"Predictive Value of Impulse Oscillometry Combined with Fractional Expiratory Nitric Oxide Test for Asthma in Preschool Children.","authors":"Junsong Chen, Jiying Xiao, Lingyue Liu, Kamran Ali, Suling Wu","doi":"10.2147/JAA.S460193","DOIUrl":"10.2147/JAA.S460193","url":null,"abstract":"<p><strong>Objective: </strong>Prediction of asthma in preschool children is challenging and lacks objective indicators. The aim is to observe and analyze the variances between impulse oscillometry (IOS) and fractional expiratory nitric oxide (FeNO) in preschool children with wheezing, establish a joint prediction model, and explore the diagnostic value of combining IOS with FeNO in diagnosing asthma among preschool children.</p><p><strong>Patients and methods: </strong>This study enrolled children aged 3-6 years with wheezing between June 2021 and June 2022. They were categorized as asthmatic (n=104) or non-asthmatic (n=109) after a 1-year follow-up. Clinical data, along with IOS and FeNO measurements from both groups, underwent univariate regression and multiple regression analyses to identify predictive factors and develop the most accurate model. The prediction model was built using the stepwise (stepAIC) method. The receiver operating characteristic curve (ROC), calibration curve, Hosmer-Lemeshow test, and decision curve analysis (DCA) were employed to validate and assess the model.</p><p><strong>Results: </strong>During univariate analysis, a history of allergic rhinitis, a history of eczema or atopic dermatitis, and measures including FeNO, R5, X5, R20, Fres, and R5-R20 were found to be associated with asthma diagnosis. Subsequent multivariate analysis revealed elevated FeNO, R5, and X5 as independent risk factors. The stepAIC method selected five factors (history of allergic rhinitis, history of eczema or atopic dermatitis, FeNO, R5, X5) and established a prediction model. The combined model achieved an AUROC of 0.94, with a sensitivity of 0.89 and specificity of 0.88, surpassing that of individual factors. Calibration plots and the HL test confirmed satisfactory accuracy.</p><p><strong>Conclusion: </strong>This study has developed a prediction model based on five factors, potentially aiding clinicians in early identification of asthma risk among preschool children.</p>","PeriodicalId":15079,"journal":{"name":"Journal of Asthma and Allergy","volume":"17 ","pages":"421-430"},"PeriodicalIF":3.2,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11088859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140910810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yen-Hsun Huang, Hsien-Chih Chiou, Chun-Hung Pan, I-Shuan Wang, Ya-Tang Liao, Sheng-Siang Su, Chiao-Chicy Chen, Chian-Jue Kuo
Background: Patients with asthma experience more physical, psychological, and financial burdens; a link between asthma and suicidality has been reported in research. Purpose: This study analyzed the medical utilization and comorbidity before their self-injurious behavior in patients with asthma. Methods: We enrolled 186,862 patients newly diagnosed with asthma between 1999 and 2013 from the National Health Insurance Research Database in Taiwan. A total of 500 case subjects had ever conducted self-injurious behaviors during the study period. Based on a nested case-control study, each case was matched with 10 controls derived from the asthma cohort to analyze differences between them and their medical use models. Results: The results indicated that, compared to the control group, the cases presented higher frequencies of outpatient visits and hospitalizations. Regarding comorbidity, the cases had more cardiovascular diseases (adjusted odds ratio [aOR]=1.58; p< 0.001), bipolar disorder (aOR=2.97; p< 0.001), depression (aOR=4.44; p< 0.001), and sleep disorder (aOR=1.83; p< 0.001) than the controls. Conclusion: The evidence-based information serves as a reference for medical staff to reduce the occurrence of self-injurious behavior in patients with asthma.
{"title":"Healthcare Utilization, Physical and Psychiatric Comorbidities Before Self-Injurious Behavior in Patients with Asthma: A Nested Case-Control Study","authors":"Yen-Hsun Huang, Hsien-Chih Chiou, Chun-Hung Pan, I-Shuan Wang, Ya-Tang Liao, Sheng-Siang Su, Chiao-Chicy Chen, Chian-Jue Kuo","doi":"10.2147/jaa.s449337","DOIUrl":"https://doi.org/10.2147/jaa.s449337","url":null,"abstract":"<strong>Background:</strong> Patients with asthma experience more physical, psychological, and financial burdens; a link between asthma and suicidality has been reported in research.<br/><strong>Purpose:</strong> This study analyzed the medical utilization and comorbidity before their self-injurious behavior in patients with asthma.<br/><strong>Methods:</strong> We enrolled 186,862 patients newly diagnosed with asthma between 1999 and 2013 from the National Health Insurance Research Database in Taiwan. A total of 500 case subjects had ever conducted self-injurious behaviors during the study period. Based on a nested case-control study, each case was matched with 10 controls derived from the asthma cohort to analyze differences between them and their medical use models.<br/><strong>Results:</strong> The results indicated that, compared to the control group, the cases presented higher frequencies of outpatient visits and hospitalizations. Regarding comorbidity, the cases had more cardiovascular diseases (adjusted odds ratio [aOR]=1.58; <em>p</em>< 0.001), bipolar disorder (aOR=2.97; <em>p</em>< 0.001), depression (aOR=4.44; <em>p</em>< 0.001), and sleep disorder (aOR=1.83; <em>p</em>< 0.001) than the controls.<br/><strong>Conclusion:</strong> The evidence-based information serves as a reference for medical staff to reduce the occurrence of self-injurious behavior in patients with asthma.<br/><br/>","PeriodicalId":15079,"journal":{"name":"Journal of Asthma and Allergy","volume":"113 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140881733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haijing Sui, Hong Shen, Chi Zhang, Minghui Wang, Zhen Zhen, Junbo Zhang
Objective: This study aimed to explore whether saliva pepsin concentration (SPC) could be regarded as a risk factor for the occurrence and unfavorable control of asthma in children with allergic rhinitis. Methods: A prospective study was conducted on a group of 20 consecutive children newly diagnosed with allergic rhinitis and asthma (referred to as the asthma group). All these children underwent fractional exhaled nitric oxide (FeNO) measurement, lung function tests, and assessment of asthma control using the 7-item Childhood Asthma Control Test (C-ACT) score. Simultaneously, a control group consisting of 20 children with simple allergic rhinitis, matched for baseline characteristics, was included. SPC measurement was performed in the two groups. Results: The SPC value was significantly higher in the asthma group than that in the control group (165.0 ± 82.8 ng/mL vs 68.4 ± 34.5 ng/mL) (P < 0.001). In the asthma group, SPC was independently associated with FeNO, the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC), and forced expiratory flow at 50% and 75% of FVC (FEF50 and FEF75) (all P < 0.05). The severity of nasal symptoms evaluated by the visual analogue scale (N-VAS) was independently associated with FEF75, the maximal mid-expiratory flow (MMEF), and C-ACT score (P < 0.05). Conclusion: Direct pepsin exposure and uncontrolled nasal symptoms may play crucial roles in the pathogenesis and progression of childhood allergic asthma. The SPC value can be considered as a risk factor for asthma in children with allergic rhinitis.
{"title":"Elevated Saliva Pepsin Concentration as a Risk Factor for Asthma in Children with Allergic Rhinitis: A Preliminary Study","authors":"Haijing Sui, Hong Shen, Chi Zhang, Minghui Wang, Zhen Zhen, Junbo Zhang","doi":"10.2147/jaa.s447145","DOIUrl":"https://doi.org/10.2147/jaa.s447145","url":null,"abstract":"<strong>Objective:</strong> This study aimed to explore whether saliva pepsin concentration (SPC) could be regarded as a risk factor for the occurrence and unfavorable control of asthma in children with allergic rhinitis.<br/><strong>Methods:</strong> A prospective study was conducted on a group of 20 consecutive children newly diagnosed with allergic rhinitis and asthma (referred to as the asthma group). All these children underwent fractional exhaled nitric oxide (FeNO) measurement, lung function tests, and assessment of asthma control using the 7-item Childhood Asthma Control Test (C-ACT) score. Simultaneously, a control group consisting of 20 children with simple allergic rhinitis, matched for baseline characteristics, was included. SPC measurement was performed in the two groups.<br/><strong>Results:</strong> The SPC value was significantly higher in the asthma group than that in the control group (165.0 ± 82.8 ng/mL vs 68.4 ± 34.5 ng/mL) (P < 0.001). In the asthma group, SPC was independently associated with FeNO, the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC), and forced expiratory flow at 50% and 75% of FVC (FEF50 and FEF75) (all P < 0.05). The severity of nasal symptoms evaluated by the visual analogue scale (N-VAS) was independently associated with FEF75, the maximal mid-expiratory flow (MMEF), and C-ACT score (P < 0.05).<br/><strong>Conclusion:</strong> Direct pepsin exposure and uncontrolled nasal symptoms may play crucial roles in the pathogenesis and progression of childhood allergic asthma. The SPC value can be considered as a risk factor for asthma in children with allergic rhinitis.<br/><br/><strong>Keywords:</strong> saliva pepsin concentration, asthma, allergic rhinitis, gastroesophageal reflux disease<br/>","PeriodicalId":15079,"journal":{"name":"Journal of Asthma and Allergy","volume":"48 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140635502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chuan T Foo, Graham M Donovan, Francis Thien, David Langton, Peter B Noble
Purpose: Bronchial thermoplasty (BT) is a bronchoscopic intervention for the treatment of severe asthma. Despite demonstrated symptomatic benefit, the underlying mechanisms by which this is achieved remain uncertain. We hypothesize that the effects of BT are driven by improvements in ventilation heterogeneity as assessed using functional respiratory imaging (FRI). Patient and Methods: Eighteen consecutive patients with severe asthma who underwent clinically indicated BT were recruited. Patients were assessed at baseline, 4-week after treatment of the left lung, and 12-month after treatment of the right lung. Data collected included short-acting beta-agonist (SABA) and oral prednisolone (OCS) use, asthma control questionnaire (ACQ-5) and exacerbation history. Patients also underwent lung function tests and chest computed tomography. Ventilation parameters including interquartile distance (IQD; measure of ventilation heterogeneity) were derived using FRI. Results: 12 months after BT, significant improvements were seen in SABA and OCS use, ACQ-5, and number of OCS-requiring exacerbations. Apart from pre-bronchodilator FEV1, no other significant changes were observed in lung function. Ventilation heterogeneity significantly improved after treatment of the left lung (0.18 ± 0.04 vs 0.20 ± 0.04, p=0.045), with treatment effect persisting up to 12 months later (0.18 ± 0.05 vs 0.20 ± 0.04, p=0.028). Ventilation heterogeneity also improved after treatment of the right lung, although this did not reach statistical significance (0.18 ± 0.05 vs 0.19 ± 0.04, p=0.06). Conclusion: Clinical benefits after BT are accompanied by improvements in ventilation heterogeneity, advancing our understanding of its mechanism of action. Beyond BT, FRI has the potential to be expanded into other clinical applications.
{"title":"Bronchial Thermoplasty Improves Ventilation Heterogeneity Measured by Functional Respiratory Imaging in Severe Asthma","authors":"Chuan T Foo, Graham M Donovan, Francis Thien, David Langton, Peter B Noble","doi":"10.2147/jaa.s454951","DOIUrl":"https://doi.org/10.2147/jaa.s454951","url":null,"abstract":"<strong>Purpose:</strong> Bronchial thermoplasty (BT) is a bronchoscopic intervention for the treatment of severe asthma. Despite demonstrated symptomatic benefit, the underlying mechanisms by which this is achieved remain uncertain. We hypothesize that the effects of BT are driven by improvements in ventilation heterogeneity as assessed using functional respiratory imaging (FRI).<br/><strong>Patient and Methods:</strong> Eighteen consecutive patients with severe asthma who underwent clinically indicated BT were recruited. Patients were assessed at baseline, 4-week after treatment of the left lung, and 12-month after treatment of the right lung. Data collected included short-acting beta-agonist (SABA) and oral prednisolone (OCS) use, asthma control questionnaire (ACQ-5) and exacerbation history. Patients also underwent lung function tests and chest computed tomography. Ventilation parameters including interquartile distance (IQD; measure of ventilation heterogeneity) were derived using FRI.<br/><strong>Results:</strong> 12 months after BT, significant improvements were seen in SABA and OCS use, ACQ-5, and number of OCS-requiring exacerbations. Apart from pre-bronchodilator FEV<sub>1</sub>, no other significant changes were observed in lung function. Ventilation heterogeneity significantly improved after treatment of the left lung (0.18 ± 0.04 vs 0.20 ± 0.04, p=0.045), with treatment effect persisting up to 12 months later (0.18 ± 0.05 vs 0.20 ± 0.04, p=0.028). Ventilation heterogeneity also improved after treatment of the right lung, although this did not reach statistical significance (0.18 ± 0.05 vs 0.19 ± 0.04, p=0.06).<br/><strong>Conclusion:</strong> Clinical benefits after BT are accompanied by improvements in ventilation heterogeneity, advancing our understanding of its mechanism of action. Beyond BT, FRI has the potential to be expanded into other clinical applications.<br/><br/><strong>Keywords:</strong> asthma, computed tomography, computational fluid dynamics, imaging, mechanism of action, pathophysiology<br/>","PeriodicalId":15079,"journal":{"name":"Journal of Asthma and Allergy","volume":"302 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140635796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In-Seon Lee, Da-Eun Yoon, Seoyoung Lee, Jae-Hwan Kang, Younbyoung Chae, Hi-Joon Park, Junsuk Kim
Purpose: Only a few studies have focused on the brain mechanisms underlying the itch processing in AD patients, and a neural biomarker has never been studied in AD patients. We aimed to develop a deep learning model-based neural signature which can extract the relevant temporal dynamics, discriminate between AD and healthy control (HC), and between AD patients who responded well to acupuncture treatment and those who did not. Patients and Methods: We recruited 41 AD patients (22 male, age mean ± SD: 24.34 ± 5.29) and 40 HCs (20 male, age mean ± SD: 26.4 ± 5.32), and measured resting-state functional MRI signals. After preprocessing, 38 functional regions of interest were applied to the functional MRI signals. A long short-term memory (LSTM) was used to extract the relevant temporal dynamics for classification and train the prediction model. Bootstrapping and 4-fold cross-validation were used to examine the significance of the models. Results: For the identification of AD patients and HC, we found that the supplementary motor area (SMA), posterior cingulate cortex (PCC), temporal pole, precuneus, and dorsolateral prefrontal cortex showed significantly greater prediction accuracy than the chance level. For the identification of high and low responder to acupuncture treatment, we found that the lingual-parahippocampal-fusiform gyrus, SMA, frontal gyrus, PCC and precuneus, paracentral lobule, and primary motor and somatosensory cortex showed significantly greater prediction accuracy than the chance level. Conclusion: We developed and evaluated a deep learning model-based neural biomarker that can distinguish between AD and HC as well as between AD patients who respond well and those who respond less to acupuncture. Using the intrinsic neurological abnormalities, it is possible to diagnose AD patients and provide personalized treatment regimens.
Keywords: Atopic Dermatitis, deep learning, functional MRI, biomarkers, personalized medicine
目的：只有少数研究关注了AD患者痒感处理的大脑机制，而且从未对AD患者的神经生物标志物进行过研究。我们旨在开发一种基于深度学习模型的神经特征，它可以提取相关的时间动态，区分AD和健康对照（HC），以及对针灸治疗反应良好和反应不佳的AD患者：我们招募了 41 名 AD 患者（22 名男性，平均年龄（±SD）：24.34±5.29）和 40 名 HC（20 名男性，平均年龄（±SD）：26.4±5.32），并测量了静息态功能磁共振成像信号。经过预处理后，38 个感兴趣功能区被应用于功能磁共振成像信号。使用长短期记忆（LSTM）提取相关的时间动态进行分类并训练预测模型。采用引导法和四倍交叉验证来检验模型的显著性：结果：在识别AD患者和HC时，我们发现辅助运动区（SMA）、扣带回后皮层（PCC）、颞极、楔前区和背外侧前额叶皮层的预测准确率明显高于偶然水平。在识别针灸治疗的高响应者和低响应者时，我们发现舌-副海马-纺锤形回、SMA、额回、PCC和楔前皮层、旁中心小叶、初级运动和躯体感觉皮层的预测准确率明显高于偶然水平：我们开发并评估了一种基于深度学习模型的神经生物标志物，它可以区分AD和HC，以及对针灸反应良好和反应较差的AD患者。利用内在的神经异常，可以诊断 AD 患者并提供个性化的治疗方案：特应性皮炎 深度学习 功能磁共振成像 生物标志物 个性化医疗
{"title":"Neural Biomarkers for Identifying Atopic Dermatitis and Assessing Acupuncture Treatment Response Using Resting-State fMRI","authors":"In-Seon Lee, Da-Eun Yoon, Seoyoung Lee, Jae-Hwan Kang, Younbyoung Chae, Hi-Joon Park, Junsuk Kim","doi":"10.2147/jaa.s454807","DOIUrl":"https://doi.org/10.2147/jaa.s454807","url":null,"abstract":"<strong>Purpose:</strong> Only a few studies have focused on the brain mechanisms underlying the itch processing in AD patients, and a neural biomarker has never been studied in AD patients. We aimed to develop a deep learning model-based neural signature which can extract the relevant temporal dynamics, discriminate between AD and healthy control (HC), and between AD patients who responded well to acupuncture treatment and those who did not.<br/><strong>Patients and Methods:</strong> We recruited 41 AD patients (22 male, age mean ± SD: 24.34 ± 5.29) and 40 HCs (20 male, age mean ± SD: 26.4 ± 5.32), and measured resting-state functional MRI signals. After preprocessing, 38 functional regions of interest were applied to the functional MRI signals. A long short-term memory (LSTM) was used to extract the relevant temporal dynamics for classification and train the prediction model. Bootstrapping and 4-fold cross-validation were used to examine the significance of the models.<br/><strong>Results:</strong> For the identification of AD patients and HC, we found that the supplementary motor area (SMA), posterior cingulate cortex (PCC), temporal pole, precuneus, and dorsolateral prefrontal cortex showed significantly greater prediction accuracy than the chance level. For the identification of high and low responder to acupuncture treatment, we found that the lingual-parahippocampal-fusiform gyrus, SMA, frontal gyrus, PCC and precuneus, paracentral lobule, and primary motor and somatosensory cortex showed significantly greater prediction accuracy than the chance level.<br/><strong>Conclusion:</strong> We developed and evaluated a deep learning model-based neural biomarker that can distinguish between AD and HC as well as between AD patients who respond well and those who respond less to acupuncture. Using the intrinsic neurological abnormalities, it is possible to diagnose AD patients and provide personalized treatment regimens.<br/><br/><strong>Keywords:</strong> Atopic Dermatitis, deep learning, functional MRI, biomarkers, personalized medicine<br/>","PeriodicalId":15079,"journal":{"name":"Journal of Asthma and Allergy","volume":"47 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140612856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gilda Zarate-Gonzalez, Paul Brown, Ricardo Cisneros
Introduction: The San Joaquin Valley (SJV) is often recognized as one of the most polluted regions in the US. Periods of pollution exposure are associated with increased health burden related to respiratory inflammation and undermined lung function, which aggravates respiratory diseases such as asthma and leads to symptoms such as coughing, wheezing, or difficulty breathing. Asthma costs US&dollar 82 billion annually in healthcare costs, missed work and school in the US. Methods: Employing a societal perspective, a cost of illness design was combined with environmental epidemiological methods to analyze the economic impact of O3, NO2, and PM2.5-related adverse respiratory health outcomes amongst SJV residents who attended the emergency department (ED) or were hospitalized in 2016. Results: Asthma exacerbations monetized value ranged from US&dollar 3353 to US&dollar 5003 per ED visit and for hospital admissions US&dollar 2584 per inpatient day for adults 65 years and older to US&dollar 3023 per child. The estimated value to society in healthcare costs, productivity losses, school absences, and opportunity costs from air pollution adverse health outcomes totaled US&dollar 498,014,124 in ED visits and US&dollar 223,552,720 in hospital admissions for the SJV population in 2016. The marginal reduction in the background concentrations of pollutants would avert 21,786 ED adverse events and 19,328 hospitalizations from the health burden on the SJV population or US&dollar 8,024,505 cost savings due to O3, US&dollar 82,482,683 from NO2 reductions, and US&dollar 46,214,702 from decreased concentration of PM2.5. Conclusion: This study provides evidence that air pollution is a negative externality that imposes substantial social, environmental, and healthcare costs on the SJV. Furthermore, the region would avert significant adverse health outcomes realizing economic savings by reducing air pollution and exposures.
Keywords: health economics, air pollution, asthma, cost of illness, public health
{"title":"Costs of Air Pollution in California’s San Joaquin Valley: A Societal Perspective of the Burden of Asthma on Emergency Departments and Inpatient Care","authors":"Gilda Zarate-Gonzalez, Paul Brown, Ricardo Cisneros","doi":"10.2147/jaa.s455745","DOIUrl":"https://doi.org/10.2147/jaa.s455745","url":null,"abstract":"<strong>Introduction:</strong> The San Joaquin Valley (SJV) is often recognized as one of the most polluted regions in the US. Periods of pollution exposure are associated with increased health burden related to respiratory inflammation and undermined lung function, which aggravates respiratory diseases such as asthma and leads to symptoms such as coughing, wheezing, or difficulty breathing. Asthma costs US&dollar 82 billion annually in healthcare costs, missed work and school in the US.<br/><strong>Methods:</strong> Employing a societal perspective, a cost of illness design was combined with environmental epidemiological methods to analyze the economic impact of O<sub>3</sub>, NO<sub>2</sub>, and PM<sub>2.5</sub>-related adverse respiratory health outcomes amongst SJV residents who attended the emergency department (ED) or were hospitalized in 2016.<br/><strong>Results:</strong> Asthma exacerbations monetized value ranged from US&dollar 3353 to US&dollar 5003 per ED visit and for hospital admissions US&dollar 2584 per inpatient day for adults 65 years and older to US&dollar 3023 per child. The estimated value to society in healthcare costs, productivity losses, school absences, and opportunity costs from air pollution adverse health outcomes totaled US&dollar 498,014,124 in ED visits and US&dollar 223,552,720 in hospital admissions for the SJV population in 2016. The marginal reduction in the background concentrations of pollutants would avert 21,786 ED adverse events and 19,328 hospitalizations from the health burden on the SJV population or US&dollar 8,024,505 cost savings due to O<sub>3</sub>, US&dollar 82,482,683 from NO<sub>2</sub> reductions, and US&dollar 46,214,702 from decreased concentration of PM<sub>2.5</sub>.<br/><strong>Conclusion:</strong> This study provides evidence that air pollution is a negative externality that imposes substantial social, environmental, and healthcare costs on the SJV. Furthermore, the region would avert significant adverse health outcomes realizing economic savings by reducing air pollution and exposures.<br/><br/><strong>Keywords:</strong> health economics, air pollution, asthma, cost of illness, public health<br/>","PeriodicalId":15079,"journal":{"name":"Journal of Asthma and Allergy","volume":"1 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140612998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Zhao, Hua Wang, Zhengjun Wu, Yunxiang Zhu, Jingsong Wang
Background: Adverse reactions induced by isoosmolar contrast medium (iodixanol) are mostly mild, with rashes and headaches being the most common. Although anaphylactic shock has been reported, no related incidents have been documented on cerebral angiography. Objective: This article reports a serious case of anaphylactic shock possibly induced by iodixanol and provides an overview of the case report. Case Summary: A 65-year-old female with persistent headaches for nearly six months and CTA examination revealed multiple intracranial aneurysms. After two treatments, she returned to the hospital for aneurysm of reexamination a month ago. Following a preoperative assessment, cerebral angiography was performed. Three minutes after the procedure, the patient experienced dizziness, increased heart rate, followed by hypotension (BP 90/43 mm Hg), a sudden drop-in heart rate (HR 68 bpm), and a drop in SpO2 to 92%. Intravenous dexamethasone for anti-allergic were administered immediately, along with therapy through oxygen-inhalation. However, the patient then developed limb convulsions, unresponsiveness, and was urgently given diazepam for sedation and sputum aspiration to maintain airway patency. Blood pressure decrease to 53/29 mm Hg, and SpO2 readings were unavailable. Intravenous dopamine to elevates blood pressure, and assists breathing by intubating in the endotracheal. After 3 minutes, as the blood pressure remained undetectable, intermittent intravenous epinephrine 1mg was administered to raise the blood pressure, gradually restoring it to 126/90 mm Hg, and SpO2 increased to 95%. The patient was diagnosed with iodixanol-induced anaphylactic shock and urgently transferred to the NICU for monitoring and treatment. The patient died despite immediate treatment. Conclusion: A 65-year-old female developed serious anaphylactic shock during cerebral angiography after receiving iodixanol. Although iodixanol is considered one of the safest iodinated contrast mediums (ICM), clinicians should be aware of its the potential for serious hypersensitivity reactions that can lead to fatal and life-threatening events.
{"title":"Case Report: A Rare Case of Iodixanol-Induced Anaphylactic Shock in Cerebral Angiography","authors":"Yang Zhao, Hua Wang, Zhengjun Wu, Yunxiang Zhu, Jingsong Wang","doi":"10.2147/jaa.s460263","DOIUrl":"https://doi.org/10.2147/jaa.s460263","url":null,"abstract":"<strong>Background:</strong> Adverse reactions induced by isoosmolar contrast medium (iodixanol) are mostly mild, with rashes and headaches being the most common. Although anaphylactic shock has been reported, no related incidents have been documented on cerebral angiography.<br/><strong>Objective:</strong> This article reports a serious case of anaphylactic shock possibly induced by iodixanol and provides an overview of the case report.<br/><strong>Case Summary:</strong> A 65-year-old female with persistent headaches for nearly six months and CTA examination revealed multiple intracranial aneurysms. After two treatments, she returned to the hospital for aneurysm of reexamination a month ago. Following a preoperative assessment, cerebral angiography was performed. Three minutes after the procedure, the patient experienced dizziness, increased heart rate, followed by hypotension (BP 90/43 mm Hg), a sudden drop-in heart rate (HR 68 bpm), and a drop in SpO2 to 92%. Intravenous dexamethasone for anti-allergic were administered immediately, along with therapy through oxygen-inhalation. However, the patient then developed limb convulsions, unresponsiveness, and was urgently given diazepam for sedation and sputum aspiration to maintain airway patency. Blood pressure decrease to 53/29 mm Hg, and SpO2 readings were unavailable. Intravenous dopamine to elevates blood pressure, and assists breathing by intubating in the endotracheal. After 3 minutes, as the blood pressure remained undetectable, intermittent intravenous epinephrine 1mg was administered to raise the blood pressure, gradually restoring it to 126/90 mm Hg, and SpO2 increased to 95%. The patient was diagnosed with iodixanol-induced anaphylactic shock and urgently transferred to the NICU for monitoring and treatment. The patient died despite immediate treatment.<br/><strong>Conclusion:</strong> A 65-year-old female developed serious anaphylactic shock during cerebral angiography after receiving iodixanol. Although iodixanol is considered one of the safest iodinated contrast mediums (ICM), clinicians should be aware of its the potential for serious hypersensitivity reactions that can lead to fatal and life-threatening events.<br/><br/>","PeriodicalId":15079,"journal":{"name":"Journal of Asthma and Allergy","volume":"42 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Weiyi Wang, John Gulliver, Sean Beevers, Anna Freni Sterrantino, Bethan Davies, Richard W Atkinson, Daniela Fecht
Background: There is an increasing body of evidence associating short-term ambient nitrogen dioxide (NO2) exposure with asthma-related hospital admissions in children. However, most studies have relied on temporally resolved exposure information, potentially ignoring the spatial variability of NO2. We aimed to investigate how daily NO2 estimates from a highly resolved spatio-temporal model are associated with the risk of emergency hospital admission for asthma in children in England. Methods: We conducted a time-stratified case-crossover study including 111,766 emergency hospital admissions for asthma in children (aged 0– 14 years) between 1st January 2011 and 31st December 2015 in England. Daily NO2 levels were predicted at the patients’ place of residence using spatio-temporal models by combining land use data and chemical transport model estimates. Conditional logistic regression models were used to obtain the odds ratios (OR) and confidence intervals (CI) after adjusting for temperature, relative humidity, bank holidays, and influenza rates. The effect modifications by age, sex, season, area-level income deprivation, and region were explored in stratified analyses. Results: For each 10 μg/m³ increase in NO2 exposure, we observed an 8% increase in asthma-related emergency admissions using a five-day moving NO2 average (mean lag 0– 4) (OR 1.08, 95% CI 1.06– 1.10). In the stratified analysis, we found larger effect sizes for male (OR 1.10, 95% CI 1.07– 1.12) and during the cold season (OR 1.10, 95% CI 1.08– 1.12). The effect estimates varied slightly by age group, area-level income deprivation, and region. Significance: Short-term exposure to NO2 was significantly associated with an increased risk of asthma emergency admissions among children in England. Future guidance and policies need to consider reflecting certain proven modifications, such as using season-specific countermeasures for air pollution control, to protect the at-risk population.
背景：越来越多的证据表明，短期环境二氧化氮（NO2）暴露与儿童因哮喘入院有关。然而，大多数研究都依赖于时间分辨的暴露信息，可能忽略了二氧化氮的空间变异性。我们的目的是调查高度分辨的时空模型得出的每日二氧化氮估计值与英格兰儿童因哮喘而紧急入院的风险有何关联：我们进行了一项时间分层病例交叉研究，研究对象包括 2011 年 1 月 1 日至 2015 年 12 月 31 日期间因哮喘紧急入院的 111,766 名英格兰儿童（0-14 岁）。通过结合土地利用数据和化学迁移模型估计值，使用时空模型预测了患者居住地的每日二氧化氮水平。在对温度、相对湿度、银行假日和流感发病率进行调整后，使用条件逻辑回归模型得出了几率比（OR）和置信区间（CI）。在分层分析中，探讨了年龄、性别、季节、地区收入贫困程度和地区的影响修正：二氧化氮暴露量每增加 10 微克/立方米，使用五天移动二氧化氮平均值（平均滞后 0-4），我们观察到哮喘相关急诊入院率增加了 8%（OR 1.08，95% CI 1.06-1.10）。在分层分析中，我们发现男性（OR 1.10，95% CI 1.07-1.12）和寒冷季节（OR 1.10，95% CI 1.08-1.12）的影响更大。不同年龄组、地区收入水平和地区的效应估计值略有不同：短期暴露于二氧化氮与英格兰儿童哮喘急诊入院风险的增加密切相关。未来的指导意见和政策需要考虑反映某些已被证实的调整措施，如采用针对不同季节的空气污染控制对策，以保护高危人群。
{"title":"Short-Term Nitrogen Dioxide Exposure and Emergency Hospital Admissions for Asthma in Children: A Case-Crossover Analysis in England","authors":"Weiyi Wang, John Gulliver, Sean Beevers, Anna Freni Sterrantino, Bethan Davies, Richard W Atkinson, Daniela Fecht","doi":"10.2147/jaa.s448600","DOIUrl":"https://doi.org/10.2147/jaa.s448600","url":null,"abstract":"<strong>Background:</strong> There is an increasing body of evidence associating short-term ambient nitrogen dioxide (NO<sub>2</sub>) exposure with asthma-related hospital admissions in children. However, most studies have relied on temporally resolved exposure information, potentially ignoring the spatial variability of NO<sub>2</sub>. We aimed to investigate how daily NO<sub>2</sub> estimates from a highly resolved spatio-temporal model are associated with the risk of emergency hospital admission for asthma in children in England.<br/><strong>Methods:</strong> We conducted a time-stratified case-crossover study including 111,766 emergency hospital admissions for asthma in children (aged 0– 14 years) between 1st January 2011 and 31st December 2015 in England. Daily NO<sub>2</sub> levels were predicted at the patients’ place of residence using spatio-temporal models by combining land use data and chemical transport model estimates. Conditional logistic regression models were used to obtain the odds ratios (OR) and confidence intervals (CI) after adjusting for temperature, relative humidity, bank holidays, and influenza rates. The effect modifications by age, sex, season, area-level income deprivation, and region were explored in stratified analyses.<br/><strong>Results:</strong> For each 10 μg/m³ increase in NO<sub>2</sub> exposure, we observed an 8% increase in asthma-related emergency admissions using a five-day moving NO<sub>2</sub> average (mean lag 0– 4) (OR 1.08, 95% CI 1.06– 1.10). In the stratified analysis, we found larger effect sizes for male (OR 1.10, 95% CI 1.07– 1.12) and during the cold season (OR 1.10, 95% CI 1.08– 1.12). The effect estimates varied slightly by age group, area-level income deprivation, and region.<br/><strong>Significance:</strong> Short-term exposure to NO<sub>2</sub> was significantly associated with an increased risk of asthma emergency admissions among children in England. Future guidance and policies need to consider reflecting certain proven modifications, such as using season-specific countermeasures for air pollution control, to protect the at-risk population.<br/><br/>","PeriodicalId":15079,"journal":{"name":"Journal of Asthma and Allergy","volume":"273 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Bronchial thermoplasty (BT) improves clinical outcomes and quality of life for patients with severe asthma and has shown sustained reductions in airway narrowing and air trapping in previous CT studies. However, there is a lack of a comprehensive analysis, including CT evaluation, of clinical outcomes in Japanese patients who have undergone BT for severe asthma. This study aimed to evaluate the impact of BT in Japanese asthma patients, with a focus on the CT metric “WA at Pi10” to assess airway disease. Methods: Twelve patients with severe persistent asthma who underwent BT were assessed using ACQ6, AQLQ, pulmonary function tests, FeNO measurement, blood sampling, and chest CT before BT and one year after the third procedure for the upper lobes. Results: The median age of the patient was 62.0 years, 7/12 (58.3%) were male, 4/12 (33.3%) used regular oral corticosteroids, and 8/12 (66.7%) received biologics. Median FEV1% was 73.6%, and median peripheral eosinophil count was 163.8/μL. After one year of BT, ACQ6 scores improved from 2.4 to 0.8 points (p = 0.007), and AQLQ scores improved from 4.3 to 5.8 points (p < 0.001). Significant improvements were also observed in asthma exacerbations, unscheduled visits due to exacerbations, FeNO, and √WA at Pi10 (p < 0.05). The baseline mucus score on the CT findings was negatively correlated with FEV1 (r = − 0.688, p = 0.013) and with the maximum mid-expiratory flow rate (r = − 0.631, p = 0.028), and positively correlated with the peripheral blood eosinophil count (r = − 0.719, p = 0.008). Changes in √WA at Pi10 after one year were positively correlated with changes in the mucus score (r = 0.742, p = 0.007). Conclusion: This study has limitations, including its single-arm observational design and the small sample size. However, BT led to a symptomatic improvement in patients with severe asthma. The validated “√WA at Pi10” metric on CT effectively evaluated the therapeutic response in Japanese asthma patients after BT.
{"title":"Usefulness of Computed Tomography for Evaluating the Effects of Bronchial Thermoplasty in Japanese Patients with Severe Asthma","authors":"Sumiko Abe, Mina Yasuda, Kazunori Tobino, Sonoko Harada, Hitoshi Sasano, Yuki Tanabe, Yuuki Sandhu, Tomohito Takeshige, Kei Matsuno, Tetsuhiko Asao, Takuto Sueyasu, Saori Nishizawa, Kohei Yoshimine, Yuki Ko, Yuki Yoshimatsu, Kosuke Tsuruno, Hiromi Ide, Haruhi Takagi, Jun Ito, Tetsutaro Nagaoka, Norihiro Harada, Kazuhisa Takahashi","doi":"10.2147/jaa.s452865","DOIUrl":"https://doi.org/10.2147/jaa.s452865","url":null,"abstract":"<strong>Background:</strong> Bronchial thermoplasty (BT) improves clinical outcomes and quality of life for patients with severe asthma and has shown sustained reductions in airway narrowing and air trapping in previous CT studies. However, there is a lack of a comprehensive analysis, including CT evaluation, of clinical outcomes in Japanese patients who have undergone BT for severe asthma. This study aimed to evaluate the impact of BT in Japanese asthma patients, with a focus on the CT metric “WA at Pi10” to assess airway disease.<br/><strong>Methods:</strong> Twelve patients with severe persistent asthma who underwent BT were assessed using ACQ6, AQLQ, pulmonary function tests, FeNO measurement, blood sampling, and chest CT before BT and one year after the third procedure for the upper lobes.<br/><strong>Results:</strong> The median age of the patient was 62.0 years, 7/12 (58.3%) were male, 4/12 (33.3%) used regular oral corticosteroids, and 8/12 (66.7%) received biologics. Median FEV<sub>1</sub>% was 73.6%, and median peripheral eosinophil count was 163.8/μL. After one year of BT, ACQ6 scores improved from 2.4 to 0.8 points (<em>p</em> = 0.007), and AQLQ scores improved from 4.3 to 5.8 points (<em>p</em> < 0.001). Significant improvements were also observed in asthma exacerbations, unscheduled visits due to exacerbations, FeNO, and √WA at Pi10 (<em>p</em> < 0.05). The baseline mucus score on the CT findings was negatively correlated with FEV<sub>1</sub> (r = − 0.688, <em>p</em> = 0.013) and with the maximum mid-expiratory flow rate (r = − 0.631, <em>p</em> = 0.028), and positively correlated with the peripheral blood eosinophil count (r = − 0.719, <em>p</em> = 0.008). Changes in √WA at Pi10 after one year were positively correlated with changes in the mucus score (r = 0.742, <em>p</em> = 0.007).<br/><strong>Conclusion:</strong> This study has limitations, including its single-arm observational design and the small sample size. However, BT led to a symptomatic improvement in patients with severe asthma. The validated “√WA at Pi10” metric on CT effectively evaluated the therapeutic response in Japanese asthma patients after BT.<br/><br/>","PeriodicalId":15079,"journal":{"name":"Journal of Asthma and Allergy","volume":"31 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号