OTULIN allies with LUBAC to govern angiogenesis by editing ALK1 linear polyubiquitin.

OTULIN coordinates with LUBAC to edit linear polyubiquitin chains in embryonic development, autoimmunity, and inflammatory diseases. However, the mechanism by which angiogenesis, especially that of endothelial cells (ECs), is regulated by linear ubiquitination remains unclear. Here, we reveal that constitutive or EC-specific deletion of Otulin resulted in arteriovenous malformations and embryonic lethality. LUBAC conjugates linear ubiquitin chains onto Activin receptor-like kinase 1 (ALK1), which is responsible for angiogenesis defects, inhibiting ALK1 enzyme activity and Smad1/5 activation. Conversely, OTULIN deubiquitinates ALK1 to promote Smad1/5 activation. Consistently, embryonic survival of Otulin-deficient mice was prolonged by BMP9 pretreatment or EC-specific ALK1Q200D (constitutively active) knockin. Moreover, mutant ALK1 from type 2 hereditary hemorrhagic telangiectasia (HHT2) patients exhibited excessive linear ubiquitination and increased HOIP binding. As such, a HOIP inhibitor restricted the excessive angiogenesis of ECs derived from ALK1G309S-expressing HHT2 patients. These results show that OTULIN and LUBAC govern ALK1 activity to balance EC angiogenesis.

Associations between Proton-Pump Inhibitor Usage, Allergy, and Asthma: An Analysis of NHANES 2005-2006.

INTRODUCTION: Acid suppression medications, such as proton-pump inhibitors (PPIs) and histamine-2 receptor antagonists, are commonly prescribed for the treatment of gastroesophageal reflux disease and other gastrointestinal disorders. However, concerns regarding potential long-term side effects are brought up by the overuse of PPIs. This study aimed to investigate the relationship between PPI usage, allergy, and asthma in the general US population. METHODS: Data of individuals aged ≥20 years who had information on PPI use and questionnaires on allergy and asthma in the US National Health and Nutrition Examination Survey (NHANES) 2005-2006 were analyzed. Univariate and multivariable logistic regression analyses were performed to determine the associations between PPI use, prevalent allergy, and asthma. RESULTS: A total of 4,481 participants (representing 198,543,007 US individuals after weighting) were included in the analyses. PPI use was not significantly associated with the presence of allergy or asthma in the general study population after adjustment. However, in females without steroid exposure, PPI use was significantly associated with increased odds of allergy (adjusted odds ratio [aOR] = 1.69, 95% confidence interval [CI]: 1.002-2.86), among which esomeprazole use was significantly associated with increased odds of allergy (aOR = 2.68, 95% CI: 1.30-5.54) and lansoprazole with increased odds of asthma (aOR = 3.44, 95% CI: 1.50-7.87) as compared to no PPI use. Duration of PPI use was not significantly associated with allergy or asthma. CONCLUSIONS: In US women without steroid exposure, PPI use is associated with increased likelihood of prevalent allergy and asthma.

The impact of climate policy uncertainty on corporate pollution Emissions--Evidence from China.

Climate change is considered one of the major systemic risks facing the world in the 21st century. To address climate change, China has adopted a series of climate policies, but the uncertainty brought about by frequent climate policy issuance has increased pressure on enterprises, which may not be conducive to enterprises reducing emissions. This paper uses data on 1211 listed companies on the A-share market in China from 2012 to 2022 to study the impact of climate policy uncertainty on enterprise pollutant emissions. The research findings show that climate policy uncertainty increases corporate pollution emissions; climate policy uncertainty mainly generates negative impacts on enterprise environmental regulation, social responsibility, and R&D investment, thereby negatively affecting enterprise emissions reduction. Further heterogeneity analysis shows that climate policy uncertainty in China has a more significant impact on non-state-owned enterprises, technology-intensive enterprises, lightly polluting enterprises, and enterprises in western regions. These findings emphasize the importance of enterprise social responsibility, environmental regulation, and R&D investment in enterprise emissions reduction and provide policy implications for Chinese enterprises to optimize their energy-saving and emission reduction strategies in the face of climate policy uncertainty.

Evaluation of Safety, Efficacy, and Compliance of Intralymphatic Immunotherapy for Allergic Rhinoconjunctivitis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Intralymphatic immunotherapy (ILIT) is an emerging type of allergen immunotherapy with fewer injections and shorter course for allergic rhinoconjunctivitis (ARC). The efficacy and safety have not been confirmed by informative and powerful evidence yet. METHODS: A systematic review and meta-analysis were conducted through electronic searching with PubMed, Web of Science, Embase, Scopus, and China National Knowledge Infrastructure (CNKI). The safety (incidence of adverse events [AEs]), compliance (percent of patients completing treatment), and clinical efficacy of ILIT were evaluated. Clinical efficacy could be assessed by improvement of subjective symptom and rescue medication use or the nasal tolerance to specific allergen. This study is registered with PROSPERO (CRD42022353562). RESULTS: 12 randomized controlled trials (RCTs) comparing ILIT with placebo and 3 trials (2 RCTs and one case-control study) comparing ILIT and SCIT were included in this review. Totally, 582 patients diagnosed as AR or ARC were enrolled. Almost all the AEs were mild-to-moderate reactions except 2 patients developed anaphylactic reactions at the intralymphatic injection dose 5,000 SQ-U in one study. ILIT got higher incidence of local AEs than placebo, but their incidence of systemic AEs was similar. ILIT was safer than SCIT (p < 0.05). Almost all the patients could complete ILIT treatment, and the most common reason for discontinuation of ILIT was AEs. The compliance of patients receiving ILIT seemed higher than patients receiving SCIT. ILIT could significantly ameliorate subjective allergic symptoms, especially for seasonal ARC, and increase nasal tolerance, similar to SCIT. CONCLUSION: ILIT was a safe and effective treatment for ARC and could achieve comparable clinical improvement with SCIT with shorter duration and higher compliance. Moreover, ILIT was safer than SCIT.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

The Role of Epithelial-Mesenchymal Transition in Chronic Rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common condition in otorhinolaryngology. It is characterized by chronic inflammation of the nasal cavity and the sinus mucosa. However, its specific pathogenesis remains unclear. Epithelial dysfunction is closely related to inflammatory airway diseases. Various evidences support that epithelial-mesenchymal transition (EMT) plays a key role in the development of CRS. OBJECTIVE: The study aimed to explore our understanding of how EMT contributes to the pathogenesis of CRS and to examine the role of several signaling pathways in EMT. METHODS: PubMed database was used to review the literature related to EMT in CRS pathogenesis. The following key words were used for the search strategy: CRS, sinusitis, nasal polyps, epithelial cells, EMT, dysfunction, cytokines, signaling pathways, pathogenesis, and therapy. RESULTS: EMT is widely present in the nasal mucosa of CRSwNP patients and contributes to the pathogenesis of the disease. However, there is no sufficient evidence for the existence of EMT in CRSsNP. Multiple signaling pathways and molecules, such as transforming growth factor-ß signaling, Wnt signaling, and hypoxia-inducible factor-1α signaling, have been found to be involved in the EMT process and promote CRSwNP. CONCLUSION: EMT is closely associated with CRS pathogenesis. Our study supports further research on epithelial EMT changes in CRS patients and provides a basis for revealing its pathogenesis and exploring new treatments.

Fibrinogen links podocyte injury with Toll-like receptor 4 and is associated with disease activity in FSGS patients.

AIM: Fibrinogen (Fg) is reported to participate in inflammation through Toll-like receptor 4 (TLR4). However, it remains unknown whether Fg might induce podocyte damage through TLR4 and be related to disease activity in patients with focal segmental glomerulosclerosis (FSGS). METHODS: We observed Fg-induced alterations in actin and apoptosis in cultured human podocytes transfected with or without TLR4 siRNA. Expression of TLR4, phospho-p38 MAPK and phospho-NF-κB p65 was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blotting, and we analysed urinary Fg levels in adriamycin-treated mice and double immunofluorescence staining for TLR4, Fg and podocin. Urinary Fg changes were also analyzed in FSGS patients under prednisone treatment. RESULTS: First, Fg dose-dependently induced actin damage and apoptosis in cultured human podocytes, with an Fg-induced increase in TLR4 expression, and TLR4 siRNA transfection prevented these effects. TLR4 knockdown inhibited activation of p38 MAPK and NF-κB p65 in podocytes. Elevated urinary Fg levels were positively correlated with albuminuria in adriamycin-treated mice, in which Fg and TLR4 colocalized and exhibited increased expression in podocytes. Additionally, elevated urinary Fg levels were positively correlated with 24-h proteinuria and foot process width in FSGS patients. Urinary Fg levels were significantly decreased in patients with complete remission but not in those without remission. CONCLUSIONS: Fg induced podocytes injury via the TLR4-p38 MAPK-NF-κB p65 pathway. In FSGS patients, urinary Fg levels reflect therapeutic response to prednisone and disease activity.

Increased expression of transcription factor Bcl-6 in chronic rhinosinusitis with nasal polyps.

B cell activation and excessive immunoglobulin (Ig) production were suggested as the key molecular events of chronic rhinosinusitis with nasal polyp (CRSwNP). However, whether T follicular cells (Tfh cells) were involved in this process has not been documented. In this study, 22 CRSwNP patients and 12 normal controls were enrolled, Bcl-6 (the key transcription factor for Tfh cell differentiation) immunoreactivity was examined by immunohistochemical staining, and the mRNA and protein expression of Bcl-6 and IL-21 was examined using qPCR, ELISA and Western blot, respectively. Moreover, the frequencies of Bcl-6(+)CD4(+) cells (Tfh cells) in polyp tissues and normal controls were measured by flow cytometry. We found that Bcl-6 mRNA and protein levels, as well as the frequencies of Bcl-6(+)CD4(+) cells were significantly increased in polyp tissues compared with normal controls. The frequencies of Bcl-6(+)CD4(+) cells were found to be significantly associated with B cell cluster formation, tissue eosinophilia, asthma comorbidity and polyp recurrence. These findings thus added a new insight into the molecular mechanisms underlying CRSwNP and raise the possibility that Tfh cells could be a novel therapeutic target for difficult-to-treat CRSwNP.

A novel mutation of DNAH5 in chronic rhinosinusitis and primary ciliary dyskinesia in a Chinese family.

The genetic factors underlying the pathogenesis of chronic rhinosinusitis (CRS) remains unclear. We herein identified four related subjects with CRS and primary ciliary dyskinesia (PCD) from geographically disperse Chinese Han communities and performed exome capture and sequencing of one affected individual and unaffected parents. We found a novel mutation in DNAH5 (c. 8030G>A) in CRS and PCD which was different from those attributed to cystic fibrosis and a defect of cilia motility in a Chinese family through exome capture and sequencing. Our findings showed that c. 8030G>A of DNAH5 may be implicated as the disease-causing gene of CRS and PCD in this Chinese family, which may expand the understanding of clinicians on the pathogenesis of CRS. Moreover, the identification of this novel mutation in DNAH5 indirectly indicates that exome capture and sequencing are beneficial in the genetic research of midget consanguinity families.

Profiles of apple allergen components and its diagnostic value in Northern China.

Background: Limited is known on the profiles of apple allergy in China. Objective: To explore the clinical significance of apple allergen components in northern China. Methods: This study recruited 40 participants and categorized into apple tolerance (n = 19) and allergy (n = 21) group. The latter was categorized into oral allergy symptoms (OAS, n = 14) and generalized symptoms (GS, n = 7). All participants underwent ImmunoCAP screening to assess sIgE levels of birch, apple, and their components. Results: The sensitization rates were 90% for Bet v 1, 85% for Mal d 1, 35% for Bet v 2, and 20% for Mal d 3. The overall positive rate for apple allergens was 97.5%, with half demonstrating mono-sensitization to Mal d 1. Birch, Bet v 1 and Mal d 1 sIgE levels had consistent areas under the curve (AUC 0.747, p = 0.037; AUC 0.799, p = 0.012; AUC 0.902, p < 0.001 respectively) in diagnosing apple allergy. The optimal cut-off values were determined to be 22.85 kUA/L (63.6% sensitivity, 85.7% specificity), 6.84 kUA/L (81.8% sensitivity, 71.4% specificity) and 1.61 kUA/L (93.8% sensitivity, 75.0% specificity), respectively. No allergens or components demonstrated diagnostic value in distinguishing between OAS and GS. Mal d 3 sensitization was correlated with mugwort allergy and higher risk of peach, nuts or legumes generalized allergy. Conclusion: Mal d 1 was major allergen and the best for diagnosing apple allergy. Mal d 3 does not necessarily indicate severe allergic reaction to apples in northern China but may indicate mugwort sensitization and an increased risk of peach, nuts or legumes allergy.

[Study on allergen components of birch pollen in Beijing area].

Objective:To explore the allergen components of birch pollen in the Beijing area and interpret its clinical significance. Methods:A total of 58 patients with birch pollen allergy were included in the cross-sectional study and divided into allergic rhinitis（AR） and allergic asthma（AA） groups according to clinical manifestations. Concentration of birch pollen allergen sIgE, as well as Bet v 1, Bet v 2, Bet v 4 and Bet v 6 sIgE were detected by ImmunoCAP immunolinked immunoassay. Differences of sIgE concentration of birch pollen allergen component in AR and AA were analyzed. Results:There were 44（75.9%） cases of AR and 14（24.1%） cases of AA were enrolled. All the 18 patients with spring pollen allergy were AR patients without AA. There were 40 cases with both spring and autumn pollen allergy, of which 26 cases（65%） were AR and 14 cases（35%） were AA. The sIgE of birch pollen allergen was level 2 or above in all subjects. 94.8% were positive for any four allergen components. 77.6% were mono-sensitized to any allergen component while 17.2% were dual-sensitized. The positive rate of Bet v 1 and/or Bet v 2 was 93.1%. The positive rates of four protein components were: Bet v 1（82.8%）, Bet v 2（29.3%）, Bet v 6（1.7%）, Bet v 4（0%）. sIgE of birch pollen was positively correlated with sIgE level of Betv 1（r=0.898, P<0.001）. The sIgE concentration of Bet v2 in AA group was significantly higher than that in AR group（[4.34±14.35] kUA/L vs [1.56±3.26] kUA/L, P<0.05）. There was no significant difference in other components. Conclusion:Bet v 1 is the main allergen component of birch pollen in the Beijing area, and Bet v 1 plus Bet v 2 can diagnose more than 90% of birch pollen allergy.

[Expert consensus on the diagnosis and treatment of respiratory diseases exacerbated by nonsteroidal anti-inflammatory drugs （2024, Chengdu）].

Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease （N-ERD） is a chronic respiratory disease characterized by eosinophilic inflammation, featuring chronic rhinosinusitis （CRS）, asthma, and intolerance to cyclooxygenase 1 （COX-1） inhibitors. The use of these medications can lead to an acute worsening of rhinitis and asthma symptoms. This condition has not yet received sufficient attention in China, with a high rate of misdiagnosis and a lack of related research. The Chinese Rhinology Research Group convened a group of leading young experts in otolaryngology from across the country, based on the latest domestic and international evidence-based medical practices to formulate this consensus.The consensus covers the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies for N-ERD, including pharmacotherapy, surgery, biologic treatments, and desensitization therapy. The goal is to improve recognition of N-ERD, reduce misdiagnosis, and enhance treatment outcomes.

Interleukin-17A contributes to the expression of serum amyloid A in chronic rhinosinusitis with nasal polyps.

The expression and regulation of serum amyloid A (SAA) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have not been well documented. This study enrolled 24 CRSwNP patients and 19 controls to evaluate the expression of SAA in polyp tissues in Chinese adult patients and investigate underlying mechanism. The levels of SAA and interleukin (IL)-17A and myeloperoxidase (MPO) in nasal tissues were detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. In addition, the mRNA expression of SAA was examined in cultured polyp epithelial cells (PECs) in the presence of various cytokines (IFN-γ, IL-4, IL-5 and IL-17A) using qRT-PCR, and the role of extracellular signal-related kinase (ERK) signalling in SAA expression was evaluated by western blot analysis. We found the levels of SAA, IL-17A and MPO were significantly upregulated in polyp tissues compared with the controls (p < 0.05), and significant correlations between SAA and IL-17A mRNA levels, as well as between SAA and MPO protein levels, were observed in polyp tissues (p < 0.05). In the in vitro culture system, IL-17A was found to significantly increase SAA mRNA expression in PECs via ERK signaling pathway, in a time- and dose-dependent manner (p < 0.05). Our results suggested a regulatory mechanism underlying excessive SAA production in polyp tissues, which might gain more insights into the pathophysiology of CRSwNP in Chinese adult patients.

Increased neutrophilia in nasal polyps reduces the response to oral corticosteroid therapy.

BACKGROUND: Nasal polyps (NPs) are characterized by eosinophilic inflammation, which is generally considered sensitive to corticosteroid treatment. OBJECTIVES: We evaluated levels of neutrophilia in NPs and investigated whether increased neutrophilia in polyp tissue affected the response to corticosteroid treatment. METHODS: We studied 3 independent cross-sectional groups of patients with NPs. Levels of infiltration by different types of inflammatory cells were determined by using immunohistochemical analyses and compared with those seen in control nasal tissues from subjects without NPs. Levels of inflammatory mediators were measured by using real-time PCR, ELISA, and FlowCytomix analyses. Patients with NPs received oral corticosteroid therapy (30 mg of prednisone once daily for 7 days); clinical parameters of efficacy were associated with NP phenotypes. RESULTS: Among patients with NPs, 76.5% had an eosinophilic phenotype, 46.0% had a neutrophilic phenotype, and 35.8% had a mixed phenotype (indicated by double staining). Overall, patients' symptoms improved after corticosteroid treatment; numbers of eosinophils and levels of their mediators (IL-4 and IL-5), but not numbers of neutrophils or levels of their mediators (IL-8 and interferon-inducible protein 10), were reduced (P< .05). After corticosteroid treatment, patients with the nonneutrophilic phenotype (neutrophil negative) had significantly greater reductions in bilateral polyp size scores, nasal congestion scores, total nasal symptom scores, and nasal resistance than patients with the neutrophilic phenotype (neutrophil positive, P< .05). CONCLUSIONS: There are different phenotypes of NPs based on the type of immune cell infiltrate and cytokines produced (eosinophilic or neutrophilic). Patients with the neutrophilic phenotype have less response to treatment with corticosteroids based on symptom scores.

[Sensitization characteristics of ragweed pollen in Beijing area].

Objective:To investigate the sensitization characteristics of ragweed pollen in patients with allergic rhinitis（AR） and（or） allergic asthma in Beijing area, and to provide basis for the prevention and treatment of ragweed pollen sensitized population. Methods:Patients with allergic rhinitis and/or asthma from January 2017 to December 2019 in the outpatient department of Allergy Department of Beijing Shijitan Hospital were retrospectively analyzed in this study. Skin prick test（SPT） was performed with ragweed pollen allergen reagents to compare different ages, genders and respiratory diseases allergen distribution, and to observe the sensitization characteristics of its population. All of the analyses were performed using SAS software version 9.4. Results:A total of 9 727 patients were enrolled in the end. The total positive rate of ragweed pollen SPT was 45.50%（4 426/9 727）, the highest positive rate was 65.54% in 13-17 years old group; The positive rate of ragweed pollen SPT was 49.79% in allergic rhinitis combined with asthma patients, followed by 46.46% in allergic rhinitis patients, and the lowest rate was 19.42% in single allergic asthma patients. There were more females than males in both ragweed pollen sensitized and non-ragweed pollen sensitized groups（P<0.05）, and the proportion was higher in 30-39 years old than in other age groups（P<0.05）. Ragweed pollen sensitization was higher than non-ragweed pollen sensitization in the allergic rhinitis group（98.49% vs 94.76%, P<0.05）. Ragweed pollen with other summer and autumn pollen allergens in patients with positive SPT, the top three were Chenopodium pollen, Humulus pollen and Artemisia grandis pollen, with positive rates of 90.42%, 89.63% and 85.40%, respectively. Ragweed combined with other pollen sensitization accounted for 99.57%（4 407/4 426）. Allergic rhinitis was the main disease in patients sensitized with ragweed pollen alone or combined with other pollens, and there was no significant difference between the two groups（94.97% vs 98.50%, P>0.05）. Conclusion:Ragweed pollen is highly sensitized in Beijing area, single ragweed pollen sensitization is rare, often combined with multiple pollen sensitization, and allergic rhinitis is the main disease.

Profiles of Birch Allergen Component Sensitization and Its Association with Pollen Food Allergy Syndrome in Northern China.

Purpose: To investigate the major allergen components associated with birch pollen allergy in northern China and elucidate clinical relevance to pollen food allergy syndrome (PFAS). Methods: Fifty-eight patients were recruited for a cross-sectional study and categorized into two groups: PFAS group and non-PFAS group, as well as apple allergy group and non-apple allergy group. The sIgE levels of birch pollen and its components, namely Bet v 1, Bet v 2, Bet v 4, and Bet v 6, were analyzed. Results: Among 58 participants, 44 individuals (75.9%) reported PFAS. 32 out of 44 (72.7%) participants reported apple allergy. Bet v 1 exhibited the highest sensitization rate at 82.8%, followed by Bet v 2 (29.3%) and Bet v 6 (1.7%). The combined sensitization rate for Bet v 1 and/or Bet v 2 was 93.1%. A total of 77.6% of the subjects demonstrated sensitization to single component, while 19.0% exhibited sensitization to two components. The sIgE levels of birch pollen and Bet v 1 were significantly elevated in PFAS group compared to non-PFAS group (p=0.001, p<0.001, respectively), as well as in apple-allergic and non-apple-allergic group (p<0.001, p<0.001, respectively). The optimal cut-off values for birch pollen and Bet v 1 sIgE were determined to be 7.09 kUA/L (with a sensitivity of 84.1% and specificity of 78.6%) and 5.11 kUA/L (with a sensitivity of 75.0% and specificity of 85.7%) when diagnosing PFAS. In terms of apple allergy, the optimal cut-off value were 9.40 kUA/L (with a sensitivity of 81.3% and specificity of 76.9%) and 6.53 kUA/L (with a sensitivity of 84.4% and specificity of 84.6%), respectively. Conclusion: The predominant sensitization pattern is mono-sensitization to Bet v 1, but when considering immunotherapy, Bet v 2 should also be taken into account. Bet v 1 serves as a valuable biomarker for diagnosing PFAS and apple allergy.

Management of allergic rhinitis improves clinical outcomes of difficult-to-treat tic disorders or attention-deficit/hyperactivity disorders.

AIMS: This case series aimed to evaluate the effects of treatment for allergic rhinitis (AR) in AR-diagnosed children with previous diagnosis of tic disorders/attention-deficit/hyperactivity disorders (TD/ADHD) but unresponsive to behavioral or medical treatment. MATERIALS AND METHODS: Between July 2016 and June 2021, children diagnosed with AR in our hospital were enrolled. All were diagnosed with TD/ADHD refractory to behavioral or medical treatment. The demography and clinical information were collected from medical records. The outcomes were visual analogue scale (VAS) for AR severity, Yale Comprehensive Tic Severity Scale (YGTSS) for TD symptoms, and Attention-Deficit Hyperactivity Screening Scale (SNAP-IV) for ADHD symptoms. RESULTS: A total of 27 children (18 boys, 9 girls) were included, with a mean age 7.4 ± 2.9 years (3 - 17 years). They had undergone behavioral or medical treatment of TD/ADHD for 3.6 ± 1.9 years but without significant improvement in TD/ADHD symptoms. After 2-6 months of systematic treatment for AR, VAS was decreased to 0.4 ± 0.1 from 0.8 ± 0.2, YGTSS to 3.5 ± 0.7 from 6.8 ± 1.4, and SNAP-IV to 0.4 ± 0.1 from 0.6 ± 0.2 (all p < 0.001). No recurrence of TD/ADHD symptoms was reported during a mean follow-up of 2.4 ± 1.1 years (0.5 - 5 years). CONCLUSION: AR treatment improves TD/ADHD outcomes in children with difficult-to-treat TD/ADHD. In TD/ADHD children who are unresponsive to behavioral or drug treatment and have AR-related symptoms, AR examination and treatment are recommended for better prognosis.

Dissolved Oxygen and Water Temperature Drive Vertical Spatiotemporal Variation of Phytoplankton Community: Evidence from the Largest Diversion Water Source Area.

In order to study the vertical distribution characteristics of phytoplankton in the Danjiangkou Reservoir, the water source of the Middle Route Project of the South-North Water Diversion, seven sampling sites were set up in the Reservoir for quarterly sampling from 2017 to 2019, and water environment surveys were conducted simultaneously. The results showed that 157 species (including varieties) were identified, belonging to 9 phyla and 88 genera. In terms of species richness, Chlorophyta had the largest number of species, accounting for 39.49% of the total species. The Bacillariophyta and Cyanobacteria accounted for 28.03% and 13.38% of the total species, respectively. From the whole Danjiangkou Reservoir, the total phytoplankton abundance varied from 0.09 × 102 to 20.01 × 106 cells/L. In the vertical distribution, phytoplankton were mainly observed in the surface-thermospheric layer (I-II layer) and the bottom layer, while the Shannon-Wiener index showed a trend of gradually decreasing from the I-V layer. The Surfer model analysis showed that there was no significant stratification in the Q site's water temperature (WT) and dissolved oxygen (DO) levels in the water diversion area during the dynamic water diversion process. A canonical correspondence analysis (CCA) showed that DO, WT, pH, electrical conductivity (Cond), chemical oxygen demand (CODMn), total phosphorus (TP), ammonia nitrogen (NH4+-N), and total nitrogen (TN) had significant effects on the vertical distribution of phytoplankton (p < 0.05). A partial Mantel analysis showed that the vertical distribution of the phytoplankton community was related to WT, and the phytoplankton community structure at the other sites, except for Heijizui (H) and Langhekou (L), was affected by DO. This study has positive significance for exploring the vertical distribution characteristics of a phytoplankton community in a deep-water dynamic water diversion reservoir.

Self-Reported Allergic Rhinitis Prevalence and Risk Factors in Employees of the China National Railway.

BACKGROUND: Allergic rhinitis (AR) is a common allergic disease globally and its prevalence is increasing year by year. This study aimed to analyze the prevalence and risk factors of self-reported AR among the Chinese National Railway train crew in the China Railway Beijing Group.METHODS: This prospective questionnaire study surveyed 1511 randomly recruited train crewmembers from 20 cities in the China National Railway network, and 494 reported having AR. A structured questionnaire was tailored, designed, and delivered electronically to all subjects. Prevalence of and risk factors for AR were analyzed based on self-reported results.RESULTS: The prevalence of self-reported AR among train crewmembers was 32.6%. Among respondents, 86.03% worked in passenger cars and 64.6% reported having worse AR symptoms while on trains. AR frequencies were 40.15% perennially and 59.85% seasonally. Among the Total Nasal Symptoms Scores (TNSS), significant differences were found between rhinorrhea and sneezing and between nasal itching and sneezing. The Rhino-Conjunctivitis Quality of Life Questionnaire (RQLQ) showed significant correlations between all seven sections. TNSS was significantly associated with the RQLQ. Scores of both the TNSS and RQLQ showed that the severity of AR symptoms (rp = 0.103) and the impact on quality of life (rp = 0.113) correlated significantly with seniority.CONCLUSIONS: The prevalence of self-reported AR among train crew working in passenger cars is higher than that of the general Chinese population. The severity of AR symptoms and the impact on quality of life are associated with seniority, meaning the number of years working on trains.Yu R-L, Ning H-Y, Lan T-F, He H, Zheng C-B, Wang X-Y, Wang H-T, Wang X-Y. Self-reported allergic rhinitis prevalence and risk factors in employees of the China National Railway. Aerosp Med Hum Perform. 2023; 94(11):821-826.

[Clinical features and screening of ACVRL1 gene in II hereditary hemorrhagic telangiectasia].

OBJECTIVE: To analyze the clinical features and pathogenic gene of the patients with hereditary hemorrhagic telangiectasia (HHT). METHODS: The clinical features of 3 HHT families were collected. And the patients were diagnosed according to clinical diagnostic analyzed criteria of HHT, the ACVRL1 gene screened and the conservation of mutation protein. RESULTS: Three probands and 1 patient were diagnostic for HHT and 2 patients were suspected. In family I, there was a missense mutation of ACVRL1 gene in c.287A > G on 2 patients, leading to the transferal of amino acids from Asn to Ser at 96(th) place. In family II, there was a missense mutation of c.1271C > T on ACVRL1 in 2 patients, leading to the transfer of amino acids from Pro to Leu at 424(th) place. In family III, there was a deletion mutation of c.147delC on ACVRL1 so as to produce only the former 53 amino acids of ALK1 protein. Through an analysis of multi-species conservation, the mutations were conserved between multiple species. By querying the National Center for Biotechnology Information (NCBI) database, we confirmed that the mutation was not of a single nucleotide polymorphism (SNP). CONCLUSION: The genetic screening of HHT patients may identify their virulence gene. And genetic screening of their offspring is helpful for the early diagnosis and prevention before disease onset.