Exploring causal relationships between inflammatory cytokines and allergic rhinitis, chronic rhinosinusitis, and nasal polyps: a Mendelian randomization study.

Objectives: Previous research has suggested connections between specific inflammatory cytokines and nasal conditions, including Allergic Rhinitis (AR), Chronic Rhinosinusitis (CRS), and Nasal Polyps (NP). However, a lack of robust research establishing the causal underpinnings of them. This Mendelian Randomization (MR) study aims to evaluate the causal relationships between 41 inflammatory cytokines and the incidence of AR, CRS and NP. Methods: This study employed a two-sample MR design, harnessing genetic variations derived from publicly accessible genome-wide association studies (GWAS) datasets. AR data was sourced from a GWAS with 25,486 cases and 87,097 controls (identifier: ukb-b-7178). CRS data originated from a GWAS encompassing 1,179 cases and 360,015 controls (identifier: ukb-d-J32). NP data was extracted from a GWAS involving 1,637 cases and 335,562 controls (identifier: ukb-a-541). The data for 41 inflammatory cytokines were obtained from an independent GWAS encompassing 8,293 participants. Inverse variance weighted (IVW), MR Egger regression and Weighted median were used to evaluate the causalities of exposures and outcomes. A range of sensitivity analyses were implemented to assess the robustness of the results. Results: The results revealed significant associations between elevated circulating levels of MIP-1α (odds ratio, OR: 1.01798, 95% confidence interval, CI: 1.00217-1.03404, p = 0.02570) and TNF-α (OR: 1.01478, 95% CI: 1.00225-1.02746, p = 0.02067) with an augmented risk of AR in the IVW approach. Heightened levels of circulating IL-2 exhibited a positive correlation with an increased susceptibility to NP in the IVW approach (OR: 1.00129, 95% CI: 1.00017-1.00242, p = 0.02434), whereas elevated levels of circulating PDGF-BB demonstrated a decreased risk of NP (OR: 0.99920, 95% CI: 0.99841-0.99999, p = 0.047610). The MR analysis between levels of 41 inflammatory cytokines and the incidence of CRS yielded no positive outcomes. Conclusion: This investigation proposes a potential causal association between elevated levels of MIP-1α and TNF-α with an elevated risk of AR, as well as an increased risk of NP linked to elevated IL-2 levels. Furthermore, there appears to be a potential association between increased levels of circulating PDGF-BB and a reduced risk of NP.

Potential causal association between aspirin use and the reduced risk of hayfever or allergic rhinitis: a Mendelian randomization study.

Background: The evidence from observational studies on the association between the use of aspirin and the risk of hayfever or allergic rhinitis is conflicting, with a dearth of high-quality randomized controlled trials. Objective: This study aims to investigate the causal relationship between aspirin use and the risk of hayfever or allergic rhinitis. Methods: We conducted a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods. We utilized publicly available summary statistics datasets from genome-wide association studies (GWAS) meta-analyses on aspirin use in individuals of European descent (n = 337,159) as the exposure variable, and a GWAS on doctor-diagnosed hayfever or allergic rhinitis in individuals from the UK Biobank (n = 83,529) as the outcome variable. Results: We identified 7 single nucleotide polymorphisms (SNPs) at genome-wide significance from the GWASs associated with aspirin use as instrumental variables (P<5×10-8; linkage disequilibrium r2 <0.1). The IVW method provided evidence supporting a causal association between aspirin use and reduced risk of hayfever or allergic rhinitis (ß = -0.349, SE = 0.1356, P = 0.01008). MR-Egger regression indicated no causal association between aspirin use and hayfever or allergic rhinitis (ß = -0.3742, SE = 0.3809, P = 0.371), but the weighted median approach yielded evidence of a causal association (ß = -0.4155, SE = 0.1657, P = 0.01216). Cochran's Q test and the funnel plot indicated no evidence of heterogeneity and asymmetry, indicating no directional pleiotropy. Conclusion: The findings of the MR analysis support a potential causal relationship between aspirin use and the reduced risk of hayfever or allergic rhinitis.

Circ0085539 Promotes Osteosarcoma Progression by Suppressing miR-526b-5p and PHLDA1 Axis.

Background: We have previously found that circ0085539/miR-526b-5p axis participated in the progression of osteosarcoma (OS). We have been interested in expanding the networking involving circ0085539 and miR-526-5p. We identified another critical downstream target of this axis, pleckstrin homology-like domain family A member 1 (PHLDA1), thus intending to uncover the interaction between the axis and PHLDA1. Methods: Live imaging of mice tumor xenografts was conducted. Immunohistochemistry (IHC) and H&E staining were performed for our in vivo experiment, while the CCK-8 assay, flow cytometry, wound healing, Transwell invasion, and clone formation were employed to assess cellular biological functions. Results: Circ0085539 was first found to be upregulated in osteosarcoma tissues and cell lines, and circ0085539 knockdown obviously suppressed proliferation and induced apoptosis. Subsequently, miR-526b-5p functionally attenuated the tumor suppressive effects induced by circ0106714 silencing on OS cells. PHLDA1 silencing significantly led to proliferation suppression, apoptosis induction, as well as the inhibition of migration, invasion, and colony formation capabilities in OS cells, which also could be restored by the miR-526b-5p inhibitor. Conclusion: Taken together, circ0085539 effectively promoted progression of osteosarcoma through sponging miR-526b-5p to release PHLDA1, strongly suggesting that in vivo intervention of circ0085539-miR-526b-5p-PHLDA1 axis could function as a promising OS-targeted therapy.

A rare case of bilateral cervical vagal neurofibromas: role of high-resolution ultrasound.

BACKGROUND: Neurofibromas originating from vagus nerves are rarely reported in the literature. In particular, plexiform neurofibromas of the bilateral cervical vagus nerve are extremely rare. CASE PRESENTATION: A 21-year-old female presented with a 2-year history of swelling on the right side of her neck. Physical examination revealed a soft-tissue mass on the right side of her neck. Ultrasonography (US) and magnetic resonance (MR) imaging showed a tumor centered in the right carotid sheath between the internal jugular vein and the common carotid artery. In addition, a similar nodular mass in the left carotid sheath was detected on US. The right mass was surgically resected; histopathological examination revealed a neurofibroma. CONCLUSIONS: US can be a valuable method for preoperative evaluation of cervical mass, as it is capable of displaying the vagus nerve and provides sufficient diagnostic information. The cervical vagal neurofibroma can manifest as solitary or multifocal lesion. Bilateral neurofibromas are usually associated with neurofibromatosis type 1 (NF1). Early diagnosis and prompt surgical treatment should be considered.

[Langerhans cell histiocytosis in children with nasal congestion as chief complain: a case report].

Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder. Here, we report a rare case of multi-system LCH in a 20-month-old children presenting nasal congestion, fever, abnormal liver function, anemia, and skin damage. The radiograph computed tomography showed an osteolytic lesion in the lateral skull base with tumor extension. Pathological biopsy was performed, and the histopathologic diagnosis was LCH. A general review of LCH, including clinical manifestations, diagnosis, treatment, and prgognosis, is presented.

[Microsatellite alternation in laryngeal squamous cell carcinomas].

OBJECTIVE: To examine the microsatellite instability and loss of heterozygosity in the pathogenic mechanism of laryngeal squamous cell carcinomas. METHOD: Forty cases squamous cell carcinomas of larynx were analyzed by comparing tumorous tissues and normal tissues around with 3 microsatellite markers from chromosome 3, 5 and 11, using PCR and PGE-AgNO3 staining. RESULT: Among the 40 cases of laryngeal squamous cell carcinomas, 87.5% (35/40) of samples showed microsatellite instability or loss of heterozygosity in one to three microsatellite markers. High frequent microsatellite abnormal occurred at D5S592, it was 70% (28/40). Then the mutation rate of D3s1228 was 52.5% (21/40). CONCLUSION: Our study revealed that tumor suppressor genes nearby chromosome 3p14 and 5q23 regions related to the pathogenesis of squamous cell carcinomas of larynx. A correlation between microsatellite alternation and stage of the tumor were found in D3s1228 and D5s592 chromosome regions.

[Construction of GJB2 mutations common in Chinese EGFP fusion protein vectors].

OBJECTIVE: To construct GJB2 gene mutations common in Chinese EGFP fusion protein vectors, and to search for better way to study the mechanism of deletion mutations in GJB2 gene. METHOD: Non-fusion protein vectors of 235delC, 299-300 del AT and 176 del 16 bp were first made by point mutation methods in vitro. Then expression part of the upper 3 mutations were amplified by PCR and the PCR products were cloned into TA cloning vector. After cutting by restriction enzymes EcoRI/BamHI, three deletion mutations were inserted into pEGFP-N1 vector. Sequencing was used to verify the validity of the fusion protein vectors. HEK293 cells were transfected with the recombinant DNA samples by the liposome complex method. RESULT: The recombined plasmids were highly expressed in HEK293 cells. Green fluorescence signals were distributed uniformly in cytoplasm. CONCLUSION: GJB2 mutations common in Chinese EGFP fusion protein vectors were constructed successfully. It may provide a better way to explore the reasons of nonsyndromic hearing loss common in Chinese.