The effect of advanced paternal age on the lifespan of male offspring in an ancient Chinese genealogical data set.

BACKGROUND: Advanced paternal age has been reported to be associated with a variety of short-term outcomes in offspring, but long-term effects are rarely examined. The present study evaluated the impact of advanced paternal age on offspring's longevity. METHODS: We studied the effect of paternal reproductive age on the lifespan of male offspring using a Chinese genealogy data set that spans 226 years of the Qing Dynasty (1683-1909). Multivariable-adjusted Cox regression analyses of 1274 men with survival data were used to calculate hazard ratios (HRs) of advanced parental age at reproduction. We also evaluated whether the lifespan of brothers differed when they were born to the same parents at different ages. RESULTS: In models adjusted for maternal age, advanced paternal age was negatively associated with the lifespan of male offspring. Individuals born to fathers aged >40 years had a 32 % higher HR of a lifespan shorter than those born to fathers aged 25-29 years (adjusted HR 1.320, 95 % CI: 1.066-1.634). The adjusted HR for offspring born to fathers aged 35-39 years was 1.232 (95 % CI: 1.013-1.500). Older brothers born to fathers aged 20-34 years had a significantly lower risk of a reduced lifespan compared with their younger brothers with fathers aged ≥35 years at reproduction (P < 0.01). CONCLUSION: Advanced paternal age at reproduction is a negative factor for male offspring's life expectancy. With the sustained increase in paternal age over the past generation, further investigation is warranted into the impact on birth outcomes and public health.

The Role of Noncoding RNA in Airway Allergic Diseases through Regulation of T Cell Subsets.

Allergic rhinitis and asthma are common airway allergic diseases, the incidence of which has increased annually in recent years. The human body is frequently exposed to allergens and environmental irritants that trigger immune and inflammatory responses, resulting in altered gene expression. Mounting evidence suggested that epigenetic alterations were strongly associated with the progression and severity of allergic diseases. Noncoding RNAs (ncRNAs) are a class of transcribed RNA molecules that cannot be translated into polypeptides and consist of three major categories, microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Previous studies showed that ncRNAs were involved in the physiopathological mechanisms of airway allergic diseases and contributed to their occurrence and development. This article reviews the current state of understanding of the role of noncoding RNAs in airway allergic diseases, highlights the limitations of recent studies, and outlines the prospects for further research to facilitate the clinical translation of noncoding RNAs as therapeutic targets and biomarkers.

Predictive Value of Nasal Nitric Oxide and Serum NOS2 Levels in the Efficacy of Subcutaneous Immunotherapy in Pediatric Patients with Allergic Rhinitis.

Background: Subcutaneous immunotherapy (SCIT) is an effective therapy for allergic rhinitis (AR), but some AR patients still do not benefit from it. Nasal nitric oxide (nNO) and inducible nitric oxide synthase (iNOS/NOS2) act important roles in AR. This study aims to explore the abilities of serum NOS2 and nNO in predicting the clinical efficacy of SCIT in AR patients. Methods: We recruited 40 healthy controls (HCs) and 120 AR patients in this study. Serum NOS2 and nNO levels were compared between the two groups. In the AR group, patients underwent and finished 1-year of SCIT, and divided into the effective and ineffective groups, and the relationships between serum NOS2 and nNO levels and efficacy of SCIT were evaluated. Results: The serum NOS2 and nNO levels were higher in AR patients than HCs. In the effective group, the serum NOS2 and nNO levels were increased than the ineffective group. ROC curves presented that a combination of serum NOS2 and nNO exhibited promising predictive ability in predicting the clinical efficacy of SCIT. Conclusions: Serum NOS2 and nNO levels were enhanced in AR patients and might affect the efficacy of SCIT. The combined use of serum NOS2 and nNO levels could be a reliable and useful method for predicting the clinical efficacy of SCIT.

Subacute dermal toxicity study of bensulfuron-methyl in Sprague-Dawley rats.

Background: Bensulfuron-methyl has recently attracted attention given its widespread use as an herbicide in crops, especially its transdermal safety. However, no dermal toxicity study of this pesticide to mammals has been reported. The present study aims to investigate subacute dermal toxicity of bensulfuron-methyl following repeated doses exposure.Methods: Forty-eight Sprague-Dawley rats were randomly divided into four groups: a normal control group and bensulfuron-methyl groups of different concentrations (250, 500, 1000 mg/kg.bw/day). The rats were topically applied with the substance dermally for 6 h per day for 28 days. At the end of the experiment, all rats were monitored for any changes in their hematological, biochemical parameters, and pathological and histological sections.Results: There were no statistically significant differences (P ≥ 0.05) in the hematological parameters and biochemical parameters. The pathological histological results of rats in the control and the highest concentration group showed no significant abnormalities. The NOAEL of subacute dermal toxicity study was found to be 1000 mg/kg.bw/day in both female and male rats.Conclusion: The result indicated that bensulfuron-methyl is probably safe for humans as a pesticide.

Circulating C-X-C Motif Ligand 13 as a Biomarker for Early Predicting Efficacy of Subcutaneous Immunotherapy in Children With Chronic Allergic Rhinitis.

Background: C-X-C motif ligand 13 (CXCL13) and B cell-activating factor (BAFF) are proven to be involved in inflammatory diseases, but their role in allergic rhinitis (AR) remains unclear. The aim of this study was to investigate the role of serum CXCL13 and BAFF in AR and their clinical values as objective biomarkers to predict the efficacy of subcutaneous immunotherapy (SCIT). Methods: We prospectively recruited 90 children with AR treated with SCIT and collected their serum specimens before SCIT. One-year follow-up was conducted for all patients, and they were categorized into effective and ineffective groups based on efficacy. The serum concentrations of CXCL13 and BAFF were detected and compared between the two groups. A validation cohort of 52 responders and 26 non-responders were further assessed for both cytokines and serum CXCL13 and BAFF levels were assayed by enzyme-linked immunosorbent assay (ELISA). Results: Eighty children completed the follow-up schedule, and 56 children were categorized into the effective group and 24 children into the ineffective group. The serum levels of CXCL13 in the effective group were clearly higher than those in the ineffective group (P < 0.05). Receiver operating characteristic (ROC) curves revealed the potential values of CXCL13 as a biomarker in predicting the response of SCIT. Further, in the validation cohort, ELISA results demonstrated that serum CXCL13 levels were increased in responders than non-responders (P < 0.05). ROC curves showed good accuracy of serum CXCL13 in predicting the efficacy of SCIT. Conclusion: Our discovery-validation study demonstrated that circulating CXCL13 might serve as a novel biomarker to predict the outcome of SCIT in childhood AR. The findings indicated that CXCL13 was involved in the pathological mechanisms of AR and made help to the fundamental therapeutic mechanism of SCIT.

Serum YKL-40 Levels Predict Endotypes and Associate with Postoperative Recurrence in Patients with Chronic Rhinosinusitis with Nasal Polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a global health concern with high heterogeneity and rate of postoperative recidivation. YKL-40 is a pivotal pro-inflammatory mediator to promote Th2 immune response which is involved in many inflammatory diseases. This study aimed to investigate the predictive value of serum YKL-40 in CRSwNP endotypes and postoperative recurrence. METHODS: We recruited 80 primary CRSwNP, 40 recurrent CRSwNP patients and 40 healthy controls (HCs) in this study, and the serum and tissue specimens were collected. The middle turbinate mucosa tissue collected from patients undergoing septoplasty was used as control. Serum YKL-40 concentrations were detected by enzyme-linked immunosorbent assay (ELISA), and tissue YKL-40 mRNA and protein levels were examined using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The difference of YKL-40 expression was compared among different group. Multivariate analysis and receiver operating characteristic (ROC) curve were performed to evaluate the value of serum YKL-40 in discriminating eosinophilic CRSwNP (eCRSwNP) and predicting postoperative recurrence. RESULTS: The serum YKL-40 levels in CRSwNP patients were higher than HCs, especially in eCRSwNP patients (p < 0.05). The elevated YKL-40 levels positively correlated with blood eosinophil percentage, tissue eosinophil counts and percentages (p < 0.05). The serum YKL-40 levels in recurrent CRSwNP patients were markedly enhanced than primary CRSwNP patients (p < 0.05). The YKL-40 mRNA and protein levels were significantly elevated in CRSwNP patients compared to HCs, especially in eCRSwNP and recurrent CRSwNP group. Multivariate analysis and ROC curve exhibited that serum YKL-40 might be a promising indicator in distinguishing CRSwNP endotypes and predicting postoperative recurrence. CONCLUSION: Our data suggested that YKL-40 might be unregulated in CRSwNP and associated with mucosal eosinophilia and recurrence. Serum YKL-40 appeared to a novel biomarker for predicting CRSwNP endotypes and postoperative recurrence of CRSwNP.