Monoclonal protein (M-protein) is a crucial biomarker for diagnosing and monitoring monoclonal gammopathies, including multiple myeloma (MM). Traditionally, electrophoresis (EP)-based methods, such as protein EP and immunofixation EP, have been widely used for M-protein detection. However, these methods can show low sensitivity and inadequate quantification of small amounts of M-protein. To overcome these challenges, EP-based methods are often combined with the quantification of serum free light chains in automated immunoassays. Advances in mass spectrometry (MS) have introduced three main approaches for sample preparation: top-down, middle-down, and bottom-up. Middle-down approaches are commonly used with matrix-assisted laser desorption/ionization time-offlight MS and liquid chromatography–electrospray ionization (LC–ESI) quadrupole time-offlight MS, whereas the bottom-up approach is typically applied with LC–ESI Orbitrap MS. A review of studies, conducted from 2014 to 2024, on plasma cell disorders that utilized MS-based methods demonstrate improvements in the sensitivity and accuracy of M-protein identification and quantification. MM remains the most frequently studied disease, with significant therapeutic advancements leading to improved outcomes. Minimal residual disease has gained attention because of its correlation with better prognoses. Monoclonal gammopathy of undetermined significance and amyloid light-chain amyloidosis are occasionally addressed, while studies on other rare diseases remain limited. This review highlights the clinical applications and advancements in MS-based methods, particularly in assessing M-protein levels for treatment responses, risk factors, and prognostic monitoring. Given their advantages—high sensitivity and specificity, automation, cost-effectiveness, and time efficiency—MS-based methods may eventually replace EP-based methods in clinical laboratories.

Background: Protein methylation has important role in regulating diverse cellular responses, including differentiation, by affecting protein activity, stability, and interactions. AZ505 is an inhibitor of the SET and MYND domain-containing protein 2 lysine methylase. In this study, we investigated the effect of AZ505 on osteoblast and osteoclast differentiation in vitro and evaluated the effect of AZ505 in vivo on the long bones in mice. Methods: Osteoblast differentiation was assessed by alkaline phosphatase (ALP) and Alizarin red staining after culturing calvarial preosteoblasts in an osteogenic medium. Osteoclast differentiation was analyzed by tartrate-resistant acid phosphatase (TRAP) staining in bone marrow-derived macrophages cultured with macrophage-colony stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL). For in vivo experiments, mice were intraperitoneally injected with AZ505 and femurs were examined by micro-computed tomography. Results: AZ505 increased ALP and Alizarin red staining in cultured osteoblasts and the expression of osteoblast marker genes, including Runx2 and osteocalcin. AZ505 resulted in decreased TRAP-staining of osteoclasts and expression of c-Fos and nuclear factor of activated T cells transcription factors and osteoclast marker genes, including cathepsin K and dendritic cell-specific transmembrane protein. Unexpectedly, in vivo administration of AZ505 markedly decreased the trabecular bone mass of femurs. In support of this catabolic result, AZ505 strongly upregulated RANKL expression in osteoblasts. Conclusions The results indicate that AZ505 has a catabolic effect on bone metabolism in vivo despite its anabolic effect in bone cell cultures. The findings indicate that cell culture data should be extrapolated cautiously to in vivo outcomes for studying bone metabolism.

OBJECTIVE: To determine a diagnostic cut-off value for the cross-sectional area (CSA) of the radial nerve using ultrasonography for radial neuropathy located at the spiral groove (SG). METHODS: Seventeen patients with electrodiagnostic evidence of radial neuropathy at the SG and 30 healthy controls underwent ultrasonography of the radial nerve at the SG . The CSAs at the SG were compared in the patient and control groups. The CSA at the SG between the symptomatic and asymptomatic sides (ΔSx–Asx and Sx/Asx, respectively) were analyzed to obtain the optimal cut-off value. The relationship between the electrophysiological severity of radial neuropathy and CSA was also evaluated. RESULTS: Among the variables examined, there were statistically significant differences in the CSA between the patient and control groups, ΔSx–Asx, and Sx/Asx at the SG. In a receiver operating characteristics analysis, the cut-off CSA was 5.75 mm² at the SG (sensitivity 52.9%, specificity 90%), 1.75 mm² for ΔSx–Asx (sensitivity 58.8%, specificity 100%), and 1.22 mm² for Sx/Asx (sensitivity 70.6%, specificity 93.3%) in diagnosing radial neuropathy at the SG. There was no significant correlation between CSA and electrophysiological severity score for either patient group. CONCLUSION: The reference value obtained for CSA of the radial nerve at the SG may facilitate investigation of radial nerve pathologies at the SG.
Diagnostic Imaging ; Humans ; Pathology ; Radial Nerve ; Radial Neuropathy* ; Reference Values ; ROC Curve ; Sensitivity and Specificity ; Ultrasonography*

OBJECTIVE: To establish the diagnostic cutoff value of ultrasonographic measurement for common fibular neuropathy (CFN) at the fibular head (FH). METHODS: Twenty patients with electrodiagnostically diagnosed CFN at the FH and 30 healthy controls were included in the study. The cross-sectional area (CSA) of sciatic nerve at mid-thigh level, common fibular nerve at popliteal fossa (PF), and common fibular (CF) nerve at FH were measured. Additionally, the difference of CF nerve CSA at the FH between symptomatic side and asymptomatic side (ΔSx–Asx), the ratio of CF nerve CSA at FH to at PF (FH/PF), and the ratio of CF nerve CSA at the FH symptomatic side to asymptomatic side (Ratio Sx–Asx) were calculated. RESULTS: CSA at the FH, FH/PF, ΔSx–Asx, and Ratio Sx–Asx showed significant differences between the patient and control groups. The cutoff value for diagnosing CFN at the FH was 11.7 mm² for the CSA at the FH (sensitivity 85.0%, specificity 90.0%), 1.70 mm² for the ΔSx–Asx (sensitivity 83.3%, specificity 97.0%), 1.11 for the FH/PF (sensitivity 47.1%, specificity 93.3%), and 1.24 for the Ratio Sx–Asx (sensitivity 72.2%, specificity 96.7%). CONCLUSION: The ultrasonographic measurement and cutoff value could be a valuable reference in diagnosing CFN at the FH and improving diagnostic reliability and efficacy.
Head* ; Humans ; Peroneal Nerve ; Peroneal Neuropathies* ; Sciatic Nerve ; Sensitivity and Specificity ; Ultrasonography*