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Context The role of B-Raf proto-oncogene (BRAF) in papillary thyroid carcinoma (PTC) with Hashimoto thyroiditis (HT) is unknown. Objective We aimed to explore risk factors affecting lymph node (LN) metastasis and interaction effect of BRAF in PTC patients with HT. Methods We retrospectively collected the data of 994 PTC patients with HT who underwent surgery at the West China Hospital. We analyzed the correlations between preoperative characteristics and LN metastasis in overall, and different BRAFV600E -mutation patients. Logistic regression was applied to analyze the risk factors for LN metastasis. Finally, we performed an interaction effect analysis to identify the interaction effect of BRAF. Results The overall LN metastasis rate was 52.71% (524/994); the overall BRAF mutation rate was 26.9% (268/994). BRAF mutation rates were significantly different in LN metastasis and nonmetastasis patients (31.7% vs 21.5%; P <.001). In all 994 patients, age, body mass index (BMI), hypertension, tumor maximum diameter, BRAF mutation, tumor location, aspect ratio, calcification, and extrathyroidal invasion were risk factors for LN metastasis (P <.05). In BRAF -mutant patients, smoking, hypertension, maximum diameter, calcification, and multifocality were risk factors for LN metastasis (P <.05). In BRAF wild-type patients, age, BMI, maximum diameter, tumor location, aspect ratio, tumor shape, calcification, and extrathyroidal invasion were risk factors (P <.05). Additionally, we found statistically significant interactions between BRAF and BMI, hypertension, maximum diameter, and calcification (P <.05), suggesting the potential interaction effect of BRAF. Conclusion BRAF is a risk factor for LN metastasis in PTC with HT. Meanwhile, BRAF can interact with age, BMI, hypertension, and calcification, which together influence LN metastasis. [ABSTRACT FROM AUTHOR]

Uromodulin (Umod, Tamm–Horsfall protein) is the most abundant urinary N-glycoprotein produced exclusively by the kidney. It can form filaments to antagonize the adhesion of uropathogens. However, the site-specific N-glycosylation signatures of Umod in healthy individuals and patients with IgA nephropathy (IgAN) remain poorly understood due to the lack of suitable isolation and analytical methods. In this study, we first presented a simple and fast method based on diatomaceous earth adsorption to isolate Umod. These isolated glycoproteins were digested by trypsin and/or Glu-C. Intact N-glycopeptides with or without HILIC enrichment were analyzed using our developed EThcD-sceHCD-MS/MS. Based on the optimized workflow, we identified a total of 780 unique intact N-glycopeptides (7 N-glycosites and 152 N-glycan compositions) from healthy individuals. As anticipated, these glycosites exhibited glycoform heterogeneity. Almost all N-glycosites were modified completely by the complex type, except for one N-glycosite (N275), which was nearly entirely occupied by the high-mannose type for mediating Umod's antiadhesive activity. Then, we compared the N-glycosylation of Umod between healthy controls (n = 9) and IgAN patients (n = 9). The N-glycosylation of Umod in IgAN patients will drastically decrease and be lost. Finally, we profiled the most comprehensive site-specific N-glycosylation map of Umod and revealed its alterations in IgAN patients. Our method provides a high-throughput workflow for characterizing the N-glycosylation of Umod, which can aid in understanding its roles in physiology and pathology, as well as serving as a potential diagnostic tool for evolution of renal tubular function. [ABSTRACT FROM AUTHOR]