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Abstract Chronic rhinosinusitis (CRS) is a prevalent inflammatory airway disease affecting over 10% of the global population, leading to considerable socio-economic impacts, especially in developing countries. The pathogenesis of CRS is multifactorial, involving potential contributions from both genetic and environmental factors. While the influence of allergic and autoimmune diseases on CRS has been observed, the causal relationships between these diseases and CRS remain unclear. We extracted data from large-scale genome-wide association studies (GWAS) and utilized a bidirectional two-sample Mendelian randomization (MR) analysis to explore the causal relationships between CRS and ten autoimmune and allergic diseases, including asthma, allergic rhinitis (AR), atopic dermatitis (AD), psoriasis, type 1 diabetes (T1D), hypothyroidism, celiac disease (CeD), multiple sclerosis (MS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Additionally, we conducted colocalization analysis to determine whether the allergic/autoimmune diseases showing statistical causal relationships with CRS are driven by the same genetic variants. The MR analysis identified that AR (OR = 1.30; 95% CI = 1.21–1.40; P = 3.26E−13), asthma (OR = 1.35; 95% CI = 1.25–1.45; P = 1.35E−14), and AD (OR = 1.17; 95% CI = 1.06–1.30; P = 0.003) were significantly associated with an increased risk of developing CRS. Interestingly, psoriasis (OR = 0.05; 95% CI = 0.01–0.37; P = 0.004) appeared to have a protective effect against CRS. Associations for T1D and hypothyroidism were also suggestive as potential risk factors for CRS. No significant associations in the reverse MR analysis, suggesting a one-directional relationship. Colocalization analysis indicated that asthma (PP.H4 = 0.99) shared the same genetic variant (IL-33 rs3939286) with CRS. In conclusion, our study confirmed the causal relationships between allergic and autoimmune diseases (AR, asthma, AD, and psoriasis) and CRS. Notably, we identified a shared genetic variant, rs3939286 in the IL-33 gene, between asthma and CRS, suggesting that targeting the IL-33 pathway may provide a therapeutic strategy for both diseases.

Abstract Background Allergic diseases exert a considerable impact on global health, thus necessitating investigations into their etiology and pathophysiology for devising effective prevention and treatment strategies. This study employs a Mendelian randomization (MR) analysis and meta-analysis to identify metabolite targets potentially associated with allergic diseases. Methods A two-sample MR analysis was conducted to explore potential causal relationships between circulating and urinary metabolites and allergic diseases. Exposures were derived from a genome-wide association study (GWAS) of 486 circulating metabolites and a GWAS of 55 targeted urinary metabolites. Outcome data for allergic diseases, including atopic dermatitis (AD), allergic rhinitis (AR), and asthma, were obtained from the FinnGen biobank in Europe (cohort 1) and the Biobank Japan in Asia (cohort 2). MR results from both cohorts were combined using a meta-analysis. Results MR analysis identified 50 circulating metabolites and 6 urinary metabolites in cohort 1 and 54 circulating metabolites and 2 urinary metabolites in cohort 2 as potentially causally related to allergic diseases. A meta-analysis of the MR results revealed stearoylcarnitine (OR 8.654; 95% CI 4.399−17.025; P = 4.06E-10) and 1-arachidonoylglycerophosphoinositol (OR 2.178; 95% CI 1.388−3.419; P = 7.15E-04) as the most reliable causal circulating metabolites for asthma and AR, respectively. Further, histidine (OR 0.734; 95% CI: 0.594−0.907; P = 0.004), tyrosine (OR 0.601; 95% CI: 0.380−0.952; P = 0.030), and alanine (OR 0.280; 95% CI: 0.125−0.628; P = 0.002) emerged as urinary metabolites with the greatest protective effects against asthma, AD, and AR, respectively. Conclusions Imbalances in numerous circulating and urinary metabolites may be implicated in the development and progression of allergic diseases. These findings have significant implications for the development of targeted strategies for the prevention and treatment of allergic diseases.

ObjectivesThe aim of this study was to assess the brain functional changes of patients with chronic rhinosinusitis with olfactory dysfunction (CRSwOD) using regional homogeneity (ReHo) of resting-state functional magnetic resonance imaging (MRI) scans, and to better explain the occurrence and development of olfactory decline in patients with chronic sinusitis provides a new idea for the study of more advanced olfactory therapy modalities.MethodsA total of 28 CRSwOD patients, 24 patients with CRS without olfactory dysfunction (CRSsOD), and 25 healthy controls (HCs) were recruited. All subjects underwent olfactory testing, clinical and brief psychological assessments, and MRI scans. A two-sided two-sample t test with AlphaSim correction (voxel-p 54 voxels) was used to detect differences between CRSwOD, CRSsOD, and HC groups.ResultsCompared with HCs, the ReHo values in traditional olfactory regions (e.g., parahippocampal gyrus (PHG), hippocampal, olfactory cortex) were increased, and ReHo values in the frontal gyrus, middle temporal gyrus, precuneus, and posterior cingulate gyrus were decreased in CRSwOD patients. The ReHo values in the precuneus and posterior cingulate gyrus of CRSwOD patients were negatively correlated with Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) scores. Compared with CRSsOD patients, the ReHo values in cerebellar regions were increased and those in the inferior temporal gyrus, precuneus, postcentral, and paracentral gyrus were decreased in CRSwOD patients. The receiver operating characteristic (ROC) curve showed that the mean ReHo values significantly differed between the CRSwOD and CRSsOD groups.ConclusionSynchronization of regional brain activity in the regions of the secondary olfactory cortex orbitofrontal cortex (OFC), temporal gyrus, precuneus, and cerebellum may be closely related to the development of olfactory dysfunction. Precuneus and posterior cingulate gyrus may be critical brain areas of action for emotional dysfunction in CRSwOD patients.

BackgroundStudies providing more evidence to guide adjuvant chemotherapy decisions in elderly colon cancer patients are expected. MethodsWe obtained data from the Surveillance, Epidemiology and End Results (SEER) database between 2004 and 2012. Kaplan-Meier survival curves were constructed to calculate the cancer-specific survival (CSS) rate, and comparisons of survival difference between different subgroups were performed using the log-rank test. Multivariate Cox proportional hazards regression models were carried out to estimate hazard ratio (HR) and 95% confidence intervals (CIs) of different clinicopathological characteristics.ResultsIn stage II colon cancer patients aged 70 years or older, the Kaplan-Meier survival analysis showed that the 5-year CSS rates of no chemotherapy and chemotherapy groups were 82.0% and 72.4%, respectively (P < 0.001). In stage III colon cancer patients aged 70 years or older, the Kaplan-Meier survival analysis showed that the 5-year CSS rates of no chemotherapy and chemotherapy groups were 50.7% and 61.3%, respectively (P < 0.001). Patients with chemotherapy receipt were independently associated with a 35.8% lower cancer-specific mortality rate (HR = 0.642, 95% CI: 0.620-0.665, P < 0.001) compared with those who did not receive chemotherapy.ConclusionsAdjuvant chemotherapy should be considered during the treatment of stage III colon cancer patients aged 70 years or older, but the chemotherapy benefit in elderly stage II colon cancer is suboptimal.

PurposeTo validate the prognostic value and evaluate the predictive value of response to adjuvant chemotherapy of perineural invasion (PNI) in node-negative colon cancer using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) 18 tumor registry database.MethodsPatients diagnosed with colon cancer from the SEER database between January 1, 2010 and December 31, 2015 were identified. Chi-square analysis was performed to evaluate different demographic and clinical features of patients between PNI-negative (PNI (−)) and PNI-positive (PNI (+)) groups. Univariate and multivariate Cox proportional hazard regression models were built to examine the relationship of demographic and clinical features and survival outcomes with the hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsIn total, 57,255 node-negative colon cancer patients were extracted from the SEER database. The receipt of chemotherapy was not an independent prognostic factor for CSS in T3 colon cancer with or without the presence of PNI (P >0.05). The receipt of chemotherapy was independently associated with 34.0% decreased risk of cancer-specific mortality compared with those without the receipt of chemotherapy in T4 colon cancer without the presence of PNI (HR = 0.660, 95%CI = 0.559–0.779, P

Intensive wave reflection occurs when the wavelengths of the incident waves and bottom undulations are in a 2:1 ratio. Existing studies have included the Bragg resonance phenomenon of waves passing over a continuous undulating bottom parallel to and oblique to the shoreline. More generally, the Bragg resonance mechanism is used as a means of coastal protection, rather than wave power generation. To focus the wave energy in a specific area, here, we propose sinusoidal sandbars of a horizontal V-shaped pattern, which is formed by two continuous undulating bottoms inclined at an angle to each other and the center axis of the angle is perpendicular to the shoreline. Based on the high-order spectral (HOS) numerical model, both the characteristics of Bragg resonance induced by the regular waves and random waves are investigated. In the scenario of regular waves, it shows that the wave-focusing effect is related to the angle of the V-shaped undulating bottom, and the optimal angle of inclination for the V-shaped undulating bottom is 162.24°. On that basis, considering the interactions between the random waves and the V-shaped undulating bottom of 162.24°, the Bragg resonance characteristics of random waves are studied. The BFI factor combining wave steepness and spectrum width can evaluate the focusing intensity of the Bragg resonance of the random waves. For BFI, in the range of 0.15–1.0, the values of Hsmax/Hs0 linearly increase with the increase of BFI.