Clinical and immunologic effects of sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, randomized, placebo-controlled study

Immunotherapy through oral routes is thought to be a valuable therapeutic option for asthma. The clinical and immunologic effects of sublingual immunotherapy (SLIT) in children with asthma caused by mites were evaluated in a double-blind, placebo-controlled study for 6 months. Patients (aged 6-12 yr) with mild-to-moderate asthma, with single sensitization to mite allergen, received either SLIT or placebo with a standardized Dermatophagoides pteronyssinus (D.p.)/D. farinae (D.f.) 50/50 extract. The cumulative dose was around 41824 IR, equivalent to 1.7 mg of D.p. and 3.0 mg of D.f. allergen. Symptom and medication scores were assessed throughout the study. Serum total immunoglobulin (Ig)E, eosinophil count, eosinophil cationic protein, specific IgE, specific IgG4, and skin sensitivity were evaluated before starting the treatment and after the treatment period. Twenty patients completed the study. At the beginning of the treatment, no differences were observed between the groups for symptom and medication scores, skin sensitivity, or immunologic parameters. After 6 months of treatment, there was a significant difference in nighttime asthma symptom scores and specific IgG4 (p < 0.05) in the SLIT group compared with the placebo group. Daytime symptom and medication scores, total IgE, eosinophil count, forced expiratory volume in 1 s, and mean evening peak expiratory flow rate reached significant differences in the SLIT group during the treatment period (p < 0.05). No severe adverse effects were reported. Our results revealed that treatment for 6 months with SLIT is clinically effective in decreasing asthmatic symptoms and medication use in children with mild-to-moderate asthma because of mite sensitivity. The clinical usefulness of this form of immunotherapy and the mechanism underlying its immunologic effects deserve further studies.     

Randomized placebo-controlled trial comparing montelukast and cetirizine for treating perennial allergic rhinitis in children aged 2–6 yr

Leukotriene receptor antagonists (LTRAs) were recently added to the method of treating allergic rhinitis (AR). However, in children under 6 yr old, there has been no study about its efficacy in treating AR. We aim to compare the clinical efficacy of montelukast, cetirizine and placebo in the treatment of children from 2 to 6 yr old with perennial allergic rhinitis (PAR), to see if there are any significant differences. Sixty children were selected and treated with montelukast, or cetirizine, or placebo once daily. The efficacy of the three agents was compared with the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and Total Symptom Score (TSS) by diary. In addition, we also examined serum IgE, serum eosinophil cationic protein (ECP), blood eosinophil counts, nasal airway resistance (NAR) and eosinophil percentage in nasal smears. The results revealed that both montelukast and cetirizine were significantly efficacious compared with placebo in NAR, eosinophil percentage in nasal smears, PRQLQ, TSS and all symptom items except nasal itching, throat itching and tearing. For nasal itching, only cetirizine was significantly efficacious. On the other hand, for night sleep quality, montelukast was significantly superior to cetirizine.     

赖氨酰氧化酶在眼部疾病的研究进展

赖氨酰氧化酶(LOX)是细胞外具有铜结合部位的氨基氧化酶,大量研究已经证实LOX可能参与许多疾病的病理发生过程。目前LOX导致疾病发展的常见变异的潜在机制仍然未知,但潜在的作用可能在于通过组织特异性的可变剪接或表达调控来影响LOX的生物学活性。但无论是在正常或病理情况下,关于眼组织中LOX的信息很少。近年有相关研究发现LOX可能参与许多眼部疾病的发生和发展,现就以近年来LOX参与的眼部疾病的研究进展做一综述。     

Calcified plaque resorptive status as determined by high-resolution ultrasound is predictive of successful conservative management of calcific tendinosis

Objective

In patients with calcific tendinosis, the morphology of calcified plaques is associated with response to conservative management. We aimed to determine changes in pain and morphology of plaques in patients with calcific tendinosis and non-arc-shaped plaques identified by high-resolution ultrasonography who received only conservative treatment.

Methods

A total of 33 patients with a mean age of 63.3 ± 10.3 years were included. Pain scores at the time of first and follow-up ultrasound were recorded, and the degree of plaque resolution was calculated.

Results

At follow-up, 90.9% (30 of 33) of patients reported improvement in pain, and 84.8% (28 of 33) patient had more than 50% elimination of plaques. Most of increased vascularity observed in color Doppler ultrasonography during 1st visit disappeared at follow-up.

Conclusions

In patients with calcific tendinosis, non-arc-shaped plaques determined by high-resolution ultrasonography are likely to resolve and conservative management is warranted.     

ACE gene polymorphism might disclose why some Taiwanese children with allergic rhinitis develop asthma symptoms but others do not

Although allergic asthma and allergic rhinitis have recently been considered to be a single disease, many questions remain unanswered. Why do some atopic patients develop asthma symptoms and others develop allergic rhinitis symptoms? Which factors play a role in the development of different allergic phenotypes? We hypothesized that angiotensin‐converting enzyme (ACE) gene polymorphism might play a role in the development of asthma phenotypes in children with allergic rhinitis. The study sample included 106 children with allergic rhinitis, but no asthma, and 105 age‐ and gender‐matched children with allergic rhinitis and asthma. Subjects of both groups exhibited the same systemic immunologic changes and allergen sensitivities. Controls consisted of 102 healthy children. The ACE genotype was determined by polymerase chain reaction. The serum total immunoglobulin E (IgE) level, allergen‐specific IgE sensitivity, and eosinophil count were also measured. The frequencies of the DD genotype were significantly higher in the children with both allergic rhinitis and asthma than in the children with allergic rhinitis but no asthma [p = 0.018; odds ratio (OR) = 3.257; (1.222–8.680)]. Results of this study suggest that ACE gene polymorphism DD genotype might play a role in the development of the asthma phenotype in children with allergic rhinitis.     

MicroRNA and mRNA profiling of cerebral cortex in a transgenic mouse model of Alzheimer’s disease by RNA sequencing

In a previous study, we found that long non-coding genes in Alzheimer’s disease (AD) are a result of endogenous gene disorders caused by the recruitment of microRNA (miRNA) and mRNA, and that miR-200a-3p and other representative miRNAs can mediate cognitive impairment and thus serve as new biomarkers for AD. In this study, we investigated the abnormal expression of miRNA and mRNA and the pathogenesis of AD at the epigenetic level. To this aim, we performed RNA sequencing and an integrative analysis of the cerebral cortex of the widely used amyloid precursor protein and presenilin-1 double transgenic mouse model of AD. Overall, 129 mRNAs and 68 miRNAs were aberrantly expressed. Among these, eight down-regulated miRNAs and seven up-regulated miRNAs appeared as promising noninvasive biomarkers and therapeutic targets. The main enriched signaling pathways involved mitogen-activated kinase protein, phosphatidylinositol 3-kinase-protein kinase B, mechanistic target of rapamycin kinase, forkhead box O, and autophagy. An miRNA-mRNA network between dysregulated miRNAs and corresponding target genes connected with AD progression was also constructed. These miRNAs and mRNAs are potential biomarkers and therapeutic targets for new treatment strategies, early diagnosis, and prevention of AD. The present results provide a novel perspective on the role of miRNAs and mRNAs in AD. This study was approved by the Experimental Animal Care and Use Committee of Institute of Medicinal Biotechnology of Beijing, China (approval No. IMB-201909-D6) on September 6, 2019.

Chinese Library Classification No. R446.1; R741.04; Q344+.13     

Presence of tumour-infiltrating FOXP3+ lymphocytes correlates with immature tumour angiogenesis in renal cell carcinomas

Background: FOXP3+ regulatory T cells (Tregs) inhibit effector T cell functions and are implicated in tumour progression. However, together with microvessel density (MVD) they remain controversial prognostic predictors for renal cell carcinoma (RCC), and potential associations have yet to be determined. The objective of this study was to determine the prognostic significance of Tregs and MVD and their potential relationship in RCCs. Design: Paraffin-embedded tissues from 62 RCC patients were analysed using immunohistochemistry to detect FOXP3+ lymphocytes, and double immunohistochemistry to detect different microvessel types in the tumour interior, rim and normal kidney tissue, and their correlation with clinicopathological characteristics. Survival analysis was also performed. Results: The presence of FOXP3+ cells in the tumour interior or the rim showed no correlation with death from RCC and other pathological characteristics. Negative correlations were noted between the immature MVD in the tumour interior or the rim and tumour size, tumour stage and overall survival; however, there was no correlation with the nuclear grade or pathological type. A positive correlation between FOXP3+ Tregs and immature MVD (r=0.363, P=0.014) and mature MVD (r=0.383, P=0.009) was confirmed in the tumour interior. However, there was no correlation between FOXP3+ Tregs and mature MVD (r=0.281, P=0.076) or immature MVD (r=0.064, P=0.692) in the tumour rim. Conclusions: In this study, a positive correlation between the presence of FOXP3+ Tregs and immature and mature MVD in RCC was confirmed, which suggests a link between suppression of immunity, tumour angiogenesis and poor prognosis.