Study on the mechanism of Fuzi in the treatment of allergic rhinitis based on network pharmacology and experimental validation

Objective:To study the key target genes and signaling pathways in the treatment of Allergic Rhinitis(AR)with Radix Aconiti Lateralis Preparata(aka Fuzi).Methods:The TCMPS and PubChem databases were used to screen the active ingredients and target genes of Fuzi using oral bioavailability and drug similarity as screening conditions,and the GeneCards database was used to screen the target genes of AR.The online tool Venny2.1 was used to screen the target genes of Fuzi for the treatment of Allergic Rhinitis;the STRING database was used to obtain the protein-protein interaction(PPI)network of drug-disease targets,and the key target genes were identified by the MCC algorithm.The potential biological processes and signaling pathways were identified by GO enrichment and KEGG enrichment analysis.Finally,animal experiments were conducted to demonstrate the therapeutic effect ofFuzi on Allergic Rhinitis.Results:The TCMSP,PubChem and GeneCards databases were used to screen the 21 active compound components of Fuzi and 68 potential therapeutic target genes of Fuzi for Allergic Rhinitis.PPI network analysis identified the top ten key target genes,namely:PTGS2,TNF,IL6,AKT1,ALB,STAT3,CCL2,CXCL8,VEGFA and JUN,GO functional and KEGG pathway enrichment analysis showed that the significantly enriched functions and pathways of Fuzi on Allergic Rhinitis were closely related to Allergic Rhinitis.Finally,animal experiments were conducted to verify that Fuzi is effective in the treatment of Allergic rhinitis.Conclusion:Increased expression of IL-6 and TNF-αin nasal mucosal tissues of patients with Allergic Rhinitis was positively correlated with indicators related to the disease activity of AllergicRhinitis.Fuzi ameliorated the inflammatory changes in mice with Allergic Rhinitis by inhibiting the activation of Toll-like signaling pathway in the nasal mucosa and decreasing the expression activity of IL-6 and TNF-α.

Sublingual immunotherapy for pediatric allergic rhinitis: The clinical evidence

Allergic rhinitis affect 10%-20% of pediatric population and it is caused by the Ig E-sensitization to environmental allergens, most importantly grass pollens and house dust mites. Allergic rhinitis can influence patient's daily activity severely and may precede the development of asthma, especially if it is not diagnosed and treated correctly. In addition to subcutaneous immunotherapy, sublingual immunotherapy(SLIT) represents the only treatment being potentially able to cure allergic respiratory diseases, by modulating the immune system activity. This review clearly summarizes and analyzes the available randomized, double-blinded, placebo-controlled trials, which aimed at evaluating the effectiveness and the safety of grass pollen and house dust mite SLIT for the specific treatment of pediatric allergic rhinitis. Our analysis demonstrates the good evidence supporting the efficacy of SLIT for allergic rhinitis to grass pollens in children, whereas trials regarding pediatric allergic rhinitis to house dust mites present lower quality, although several studies supported its usefulness.

Pediatric allergic conjunctivitis and allergic rhinitis

Objective： To assess the relationship between allergic conjunctivitis（AC） and allergic rhinitis（AR） in pediatric ophthalmology and E.N.T outpatient clinic. Methods：Eight hundred and ninety two patients were enrolled in survey during Mar. 2005-Jan. 2007, 407 allergic conjunctivitis cases were placed in the ophthalmology clinic group and 485 allergic rhinitis cases were from the E.N.T clinic. The comorbid disorders, histories, symptoms, signs of patients were recorded. Type 1 allergy was tested in 479 cases by a specific IgE antibody blood test. Eosinophils were detected in superficial conjunctival scrapings of the superior tarsal conjunctiva and mucosa surface scrapings of middle nasal meatus in 88 cases with both diseases. Results：302（74%）, 374（92%）, 116（29%） in 407 cases with allergic conjunctivitis had concomitant eczema, rhinitis and asthma, respectively; 334（69%）, 430（89%）, 145（30%） in 485 cases with allergic rhinitis had concomitant eczema, allergic conjunctivitis and asthma, respectively. The prevalence of allergic conjunctivitis concomitant allergic rhinitis and allergic rhinitis concomitant allergic conjunctivitis had no significant difference（x2=2,6, P 〉 0.05）. The prevalence of allergic conjunctivitis and allergic rhinitis concomitant eczema and asthma also had no significant difference （x2=3.08; x2=0.21, P 〉 0.05）. The degree of severity of two kinds of disease symptoms is not parallel, in the patients with seasonal allergic conjuctivitis（SAC） and perennial allergic conjunctivitis（PAC）, the clinical signs of AR were always severer（x2=258.2, P 〈 0.05） than those of AC. However, the results coincided with the cases with vernal keratoconjuctivitis（VKC）（x2=66.5, P 〈 0.05）; Eosinophils were revealed in 50（57%） conjunctival scrapings and nasal mucosa scrapings（x2=1.5, P〉 0.05）, 47（53%） cases had positive results in both scrapings. The main aeroallergens were house dust mites, house dust and fungi, and the main food-allergens were fish, crab and shrimp. Conclusion：The two disorders were shown to share more similarities than differences, as suggested that allergic conjunctivitis should be considered in future guidelines on preventing the development of rhinitis and asthma in children.

Nasal airflow of patient with septal deviation and allergy rhinitis

A numerical simulation of a patient’s nasal airflow was developed via computational fluid dynamics.Accordingly,computerized tomography scans of a patient with septal deviation and allergic rhinitis were obtained.The three-dimensional(3D)nasal model was designed using InVesalius 3.0,which was then imported to(computer aided 3D interactive application)CATIA V5 for modification,and finally to analysis system(ANSYS)flow oriented logistics upgrade for enterprise networks(FLUENT)to obtain the numerical solution.The velocity contours of the cross-sectional area were analyzed on four main surfaces:the vestibule,nasal valve,middle turbinate,and nasopharynx.The pressure and velocity characteristics were assessed at both laminar and turbulent mass flow rates for both the standardized and the patient’s model nasal cavity.The developed model of the patient is approximately half the size of the standardized model;hence,its velocity was approximately two times more than that of the standardized model.

A fifteen-year review of skin allergy testing in Irish patients with symptomatic rhinitis

Objective:Our objective was to review skin prick allergy testing(SPAT)results in patients with symptomatic rhinitis in an Irish population.Methods:A fifteen-year retrospective review of our database of symptomatic patients with rhinitis was performed.All patients who had SPAT performed during this interval were included.Data was analysed in terms of demographics and dominant allergens.Results:1158 patients were included.617 Females vs 541 Males.Age range five to eighty-five years old.Mean age thirty-four years.49%of our patients tested positive to at least one aeroallergen.The most common allergens were dust mites(23%)and timothy grass(22%).Patients born during the Irish pollen season(April-July)were between 5 and 7 times more likely to be sensitive to timothy and ryegrass pollens compared to others tested.241 patients had both SPAT and serum allergen specific IgE testing(SASIgET)performed;positive results were consistent between both groups.Conclusion:Results demonstrated that half of our patients with symptomatic rhinitis had allergen sensitisation.Dust mites and grass were the main allergens in our area.Our nurse led clinic has allowed efficient patient education and the development of a unique Irish SPAT database.Retesting a patient with a known allergy test result it is not indicated.

Examination of Homologies between COVID-19 Vaccines and Common Allergens:The Potential for T Cell-mediated Responses for Allergic Rhinitis and Asthma

As the SARS-CoV-2 virus shares relatively large protein sequences homologous to grass pollens,dust mites,and molds,our objective was to assess the potential overlap between the COVID-19mRNA vaccines fromPfizer-BioNtech andModerna and known allergens.We found 7 common allergens with potential for cross-reactivity with the Pfizer vaccine and 19 with theModerna vaccine,including common grasses,molds,and dust mites.T-cell mediated antigen cross-reactivity between viruses and allergens is a relatively new area of study in clinical immunology;a discipline that may be particularly useful regarding the SARS-CoV-2 virus and the allergic response in humans.These results suggest that vaccination with the Pfizer-BioNtech andModerna COVID-19 vaccinesmay contribute to T-cell cross-reactivity with allergens that impact allergic asthma and allergic rhinitis.Further research should assess the clinical implications of COVID-19 vaccination on the severity and symptomatology of the allergic disease,in addition to natural viral infection.

Treatment of 60 Cases of Allergic Rhinitis with Acupuncture and Moxibustion

采用针刺加艾灸治疗过敏性鼻炎60例,临床治愈43例,有效15例,无效2例,总有效率96.7%。

45例尘螨过敏患者冲击免疫治疗的临床安全性分析

目的对45例尘螨过敏患者进行冲击免疫治疗的临床安全性分析,为冲击免疫治疗的临床应用积累临床经验。方法共纳入2021年1月到2022年8月在变态反应门诊采用4日剂量递增方案行冲击免疫治疗的尘螨过敏患者45例,统计分析其人群特征及不良反应发生情况,并比较不同特征人群间(分别根据性别、年龄、总IgE、是否单一尘螨过敏及是否单一呼吸系统过敏进行分组)不良反应发生情况的差异。结果45例患者中男女比例约为1∶1,年龄中位数为9(7.0,17.5)岁,97.8%的患者为过敏性鼻炎,其中75%合并支气管哮喘,绝大多数(86.7%)患者有过敏家族史。95.1%存在血清总IgE的升高(>60 KU/L),其中大部分患者尘螨sIgE均在3级以上(户尘螨80.5%,粉尘螨85.4%),88.9%的患者尘螨皮内试验均为4+。不良反应发生方面,35.6%(16/45)患者出现局部反应,剂量递增阶段次均局部不良反应发生率为7.5%(27/360);其中大部分(12例,占75%)在4天剂量递增过程中仅出现1次局部反应。出现速发型局部反应(主要表现为注射部位风团)发生率为20%(9/45),迟发型局部反应(主要表现为注射部位红肿、硬结)发生率为26.7%(12/45)。8例(17.8%)出现全身不良反应,剂量递增阶段次均全身不良反应发生率为3.3%(12/360);全身反应均为轻中度,其中绝大部分为Ⅰ级(轻度)不良反应(7例,占87.5%),仅1例为Ⅱ级(中度)不良反应,占12.5%,未发生Ⅲ级~Ⅳ级严重全身不良反应。绝大部分全身反应为迟发型(7例,占87.5%),仅出现1例速发型全身反应,考虑不除外与过敏原注入小血管相关。大部分(6例,占75%)在4天剂量递增过程中仅出现1次全身反应。组间不良反应比较结果提示,各组间局部不良反应及全身不良反应的发生率未见明显差异,≥18岁组比18岁以下组发生局部不良反应的风险接近有统计学差异(χ^(2)=3.519,P=0.061)。结论本研究纳入45例接受尘螨变应原冲击免疫治疗的患者,部分发生轻中度全身不良反应,但未发生严重全身过敏反应。该结果将为冲击免疫治疗的临床应用和推广提供临床数据和实践经验。

OBSERVATION ON THE CURATIVE EFFECT OF ACUPUNCTURE ON TYPE I ALLERGIC DISEASES

In a comparative study on treatment of type Ⅰ allergic diseases,acupuncture and desensitizationtherapies were performed in 143 cases.The results showed that acupuncture therapy had an ex-tensive and remarkable action against type Ⅰ allergic reaction.The curative effect was higher inthe acupuncture group than in the desensitization group in allergic asthma,allergic rhinitis andchronic urticaria.

Probiotics and allergic diseases

The prevalence of allergic diseases including atopic dermatitis,asthma,allergic rhinitis(AR)and food allergy is increasing worldwide and they cause a big economic and social burden.Understanding of reasons thatcontribute to the etiology of allergic diseases as well as new treatment approaches are very important for the follow-up and prevention of these diseases.In recent years,probiotics seem to be promising for allergic diseases.The effect of probiotics in the prevention and treatment of eczema is more extensively studied,but little is known about the association of the microbial flora of the host and allergic airway diseases and the efficacy of probiotics in decreasing the symptoms of patients with asthma and rhinitis.Hitherto,there is no strong evidence for use of probiotics in the treatment of eczema;however,administration of probiotics in breastfeeding mothers in the prenatal period and infants in the postnatal period can be accepted as a safe and helpful option in the prevention of eczema.In contrast,there is not yet reliable evidence or recommendations on use of probiotics for the prevention or treatment of asthma,AR,food allergy,and anaphylaxis currently.More standardized studies should be performed with different strains of probiotics to evaluate the protective and therapeutic effects of probiotics on other allergic diseases as well as eczema.In this review,the relationship between allergy and probiotics is handled in the light of current literature.

树突状细胞来源外泌体在变应性鼻炎中的研究进展

变应性鼻炎(AR)是耳鼻喉科常见疾病。尽管其不是一种危及生命的严重疾病,但它是许多并发症的基础,是哮喘控制不佳的主要风险因素。常年性AR对整个社会生产力和生活质量的负面影响并不亚于哮喘。在AR的发病机制中树突状细胞(DC)扮演着重要的角色。DC来源的外泌体(DEX)不仅具有DC的生物学特性,还可以促进T细胞的启动和活化以及2型辅助T(Th2)细胞的成熟和分化。DEX可以呈递过敏原并参与过敏性免疫反应,能通过多个环节来调节AR中的信号转导。DEX携带的抗过敏药能够减轻AR的过敏性气道炎症并有效治疗Th2细胞介导的AR,因此,DEX在AR的发病机制和治疗中具有重要作用。

Allergies in Children: What’s New?—A Cross-Sectional Descriptive Study

Background: The prevalence of respiratory allergies is increasing worldwide, with important consequences especially for little children. Objective: The aim of this study was to assess the prevalence of respiratory allergies, such as rhinitis and asthma, and to point out the risk factors and their relationship with allergic diseases in a specific area of Northern Italy. Methods: 110 children, male and female, from our outpatient service for allergic children, between 3 and 17 years old, were examined. After a skin prick test and a nasal cytology, the written questionnaire of the International Study of Asthma and Allergies in Childhood was filled by parents together with their children. Results: 110 children were examined. 74% of children had rhinitis and 71% asthma. 88 patients were allergic, grass pollen and house dust mite was the most frequent allergens. A family history of atopy, family background, geographic area, active and passive smoking and home pets were associated to allergies. Older children (6 - 15 years old) had more often rhinitis associated with asthma and conjunctivitis as compared to younger. 21 Children were also affected by non allergic rhinitis. Conclusions: Respiratory allergies are widespread and associated to a low quality of life among little children. Sensitization to Ragweed is increasing with important consequences. Rhinitis precedes the onset of asthmatic symptoms. Moreover non allergic rhinitis is increasing and frequently underdiagnosed.

壮医特色优势技术组合治疗过敏性鼻炎临床观察

目的评价以壮医莲花针疗法、壮医药线点灸疗法、壮医刮痧以及壮医刺血疗法联合的壮医特色优势技术组合治疗方法对过敏性鼻炎(AR)患者的临床效果。方法选取广西中医药大学第一附属医院2018年11月—2019年9月收治的80例AR患者,随机分为对照组(40例)与壮医组(40例),对照组采取常规西药治疗,壮医组采取壮医特色优势技术组合治疗。比较两组患者临床治疗情况。结果两组患者治疗前AR症状积分以及血清IgE、白细胞介素-4(IL-4)含量水平对比,差异均无统计学意义(P>0.05);治疗后,壮医组患者AR症状积分明显低于对照组,血清IgE、IL-4含量水平明显低于对照组(P<0.05)。壮医组临床疗效为97.50%(39/40),高于对照组的75.00%(30/40)(P<0.05)。结论壮医特色优势技术组合对AR患者临床疗效显著,能明显降低患者AR症状积分、血清IgE以及IL-4含量水平,具有临床推广价值。

北京丰台地区变应性鼻炎患者变应原血清IgE检测结果分析

目的调查北京丰台地区变应性鼻炎(AR)的主要吸入性变应原。方法回顾分析2016年1月至2019年12月本院收治的1038例北京丰台地区确诊的AR患者的临床资料,按照年龄分为成人组(18~76岁,n=821)和儿童组(5~17岁,n=217),按照性别分为男性组(n=602)与女性组(n=436)。所有患者均行血清特异性IgE检测,分析变应原总体分布情况,比较儿童组与成人组及男性组与女性组的变应原分布情况。结果变应原血清特异性IgE阳性率前5位的变应原分别为屋尘螨、粉尘螨、艾蒿、矮豚草、葎草。儿童组前5位变应原依次为:屋尘螨、粉尘螨、藜/反枝苋、艾蒿、葎草;成人组中前5位的变应原依次为:屋尘螨、粉尘螨、艾蒿、矮豚草、葎草。男性组前5位的变应原依次为:粉尘螨、屋尘螨、艾蒿、矮豚草、葎草;女性组前5位的变应原依次为:屋尘螨、粉尘螨、艾蒿、矮豚草、葎草。结论屋尘螨、粉尘螨、植物花粉是北京丰台地区最重要的变应原。

基于网络药理学和实验验证探讨附子治疗变应性鼻炎的作用机制研究

目的:研究附子治疗变应性鼻炎(allergic rhinitis,AR)的关键作用靶点基因和信号通路。方法:使用TCMPS和PubChem数据库,用口服生物利用度和药物相似度作为筛选条件筛选出附子的活性成分及作用靶点基因,使用GeneCards数据库筛选出AR的靶点基因。利用在线工具Venny2.1筛选出附子治疗AR的作用靶点基因;利用STRING数据库获取药物疾病作用靶点的蛋白互作(Protein-protein interaction,PPI)网络,通过MCC算法找出关键靶点基因。通过GO富集和KEGG富集分析找到潜在的生物学过程和信号通路。最后,进行了动物实验证明附子对AR的治疗作用。结果:使用TCMSP、PubChem和GeneCards数据库筛选出附子中21种活性化合物成分和附子对AR的潜在治疗靶点基因68个。PPI网络分析找出前十个关键靶点基因,分别为:PTGS2、TNF、IL6、AKT1、ALB、STAT3、CCL2、CXCL8、VEGFA和JUN。GO功能和KEGG通路富集分析显示附子对AR的作用靶点显著富集的功能和通路与AR密切相关。最后通过动物实验验证附子对AR的治疗是有效的。结论:AR患者鼻黏膜组织中IL-6和TNF-α的表达增加,与变应性鼻炎疾病活动相关指标呈正相关。附子通过抑制小鼠鼻黏膜中Toll样信号通路的活化,降低IL-6和TNF-α的表达活性,从而改善了AR小鼠的炎症改变。

解读欧洲变态反应与临床免疫学会发表的《儿童鼻炎意见书》

2013年9月《European Journal of Allergy and Clinical Immunology》杂志发表了《儿童鼻炎意见书》。本意见书由欧洲变态反应与临床免疫学会儿童鼻炎工作组Roberts等11位学者共同完成。该意见书在收集分析相关文献的基础上,参考医学专家的意见,对推荐等级进行分级,充分反映所依赖数据的可靠程度。此意见书旨在为儿童鼻炎的诊断与治疗提供循证医学意见,主要针对社区全科医师、实习医师、儿科医师、耳鼻咽喉头颈外科医师和变态反应科医师。我们将该意见书与《变应性鼻炎及其对哮喘的影响》、《欧洲鼻-鼻窦炎和鼻息肉意见书》及我国制定的儿童变应性鼻炎诊断和治疗指南进行比较,借以解读。

重视变应性鼻炎最轻持续性炎症反应的药物治疗

多年来,对变应性鼻炎患者进行药物治疗的目的多以控制症状为主,疗效评价标准也以症状改善程度为主。《变应性鼻炎及其对哮喘的影响》（Allergic Rhinitis and Its Impacton Asthma，ARIA，2001）指南推荐的病情分类和阶梯性治疗方案也多以症状为基础，因此对症状控制的程度也成为评价某一药物疗效的“金标准”，一旦症状得以控制，药物治疗也随之停止。但最近公布的ARIA（2008）”勺虽调，对经过药物控制，症状消失或仍有轻微症状者仍应继续给予与药物治疗。

苍耳子鼻炎滴丸联合正性激励治疗对青少年过敏性鼻炎疗效及其对CRP、过敏测试影响的临床研究

目的观察苍耳子鼻炎滴丸联合正性激励治疗对青少年过敏性鼻炎疗效及其对CRP、过敏测试影响。方法选取本院2022年1-7月收治的60例过敏性鼻炎患者为研究对象,按照双色球随机分组法均分为两组,对照组采取苍耳子鼻炎滴丸治疗,观察组采取苍耳子鼻炎滴丸联合正性激励治疗,比较两组患者临床治疗效果。 结果观察组患者治疗24h后、治疗1周后视觉模拟评分(VAS)以及血清C反应蛋白(CRP)、不良反应发生率均低于对照组,观察组患者治疗后鼻腔通气面积、纤毛运动速率、鼻腔阻力等鼻腔生理功能均优于对照组,数据差异明显(P<0.05)。结论青少年过敏性鼻炎采取苍耳子鼻炎滴丸联合正性激励治疗可显著提升治疗效果。

标准化尘螨变应原疫苗治疗变应性鼻炎一年的疗效和安全性研

目的评价标准化尘螨变应原免疫治疗变应性鼻炎的疗效及安全性。方法60例螨过敏变应性鼻炎患者随机分为免疫治疗组30例和药物治疗组30例。通过症状评分、药物评分、鼻炎相关生活质量评分和不良反应分级评价免疫治疗的疗效和安全性。结果经过1年治疗后,免疫治疗组症状评分和药物评分较治疗前均明显减少(P<0.01),与药物治疗组相比亦有显著性差异(P<0.01)。同时,免疫治疗组患者的鼻炎相关生活质量明显改善。所有免疫治疗病例未出现严重不良反应。结论标准化螨变应原免疫治疗可安全有效地治疗变应性鼻炎。

特异性免疫治疗变应性鼻炎疗效的动态评估及其对哮喘的影响

【目的】探讨变应性鼻炎患者特异性免疫治疗(SIT)效果及其在防治支气管哮喘中的意义。【方法】对167例螨过敏的持续性变应性鼻炎患者,进行免疫治疗,检测各治疗时期患者血清总免疫球蛋白E(TIgE)、特异性免疫球蛋白E(SIgE)和嗜酸性粒细胞阳离子蛋白(ECP)浓度,并评估其过敏症状的变化。【结果】变应性鼻炎特异性免疫治疗后症状改善(P<0.01);儿童变应性鼻炎SIT效果较成人好(P<0.01)。此外,观察期满3年的49例接受系统免疫治疗的患者与未系统治疗患者23例发现,前者继发哮喘的几率低于后者,两者比较差异有统计学意义(P<0.01);对合并有哮喘的AR患者经SIT后,哮喘症状体征有改善;患者血清TIgE、SIgE和ECP在SIT治疗后水平逐渐降低。【结论】对儿童变应性鼻炎患者有明确变应原者,免疫治疗应予以考虑;检测患者血清TIgE、SIgE和ECP可了解SIT的疗效;对变应性鼻炎进行SIT对防治哮喘有重要意义。