Background: Vitamin D deficiency has been linked to increased risks of fractures and cardiovascular (CV) events, but the clinical relevance of the ‘insufficiency’ range remains unclear. We investigated CV and fracture risks across vitamin D levels, with a focus on the insufficiency range. Methods: Using UK Biobank data, we analyzed 375,044 participants aged 40 to 69 years. Vitamin D status was categorized as deficient (<50 nmol/L), insufficient (≥50 to <75 nmol/L), or sufficient (≥75 nmol/L). Outcomes included three-point major adverse cardiovascular events (3P-MACE; myocardial infarction, stroke, and CV mortality) and major osteoporotic fractures, assessed via hospital records, registries, and death certificates. Results: The vitamin D-deficient group had an increased risk of CV events (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.11 to 1.24) and fractures (aHR, 1.09; 95% CI, 1.01 to 1.18) compared to the vitamin D-sufficient group. Within the deficient group, the severely deficient group (<30 nmol/L) exhibited a markedly higher risk (aHR, 1.29; 95% CI, 1.21 to 1.37 for 3PMACE; and aHR, 1.20; 95% CI, 1.10 to 1.32 for fractures). In contrast, the vitamin D-insufficient group (50 to 75 nmol/L) showed no significant increase in the risk of either outcome, with no clear benefit or harm observed. Spline curve analysis revealed a negative correlation between vitamin D levels and risk, which was observed only within the deficient range and not within the insufficient range. Conclusion Vitamin D deficiency is strongly associated with increased CV disease and fracture risks, whereas the insufficiency range shows no significant risk or benefit, raising questions about its clinical relevance.

Purpose: Lidocaine, a type of local anesthetic, is used widely to suppress pain during intra-articular injections, but many studies have suggested that lidocaine is toxic to the articular cartilage. This study examined the biological changes that occur when chondrocytes are exposed to lidocaine to determine the protective effect of human placenta hydrolysate (HPH) on chondrocytes. Materials and Methods: SW1353 cells, human-derived chondrocytes, were treated with lidocaine and HPH to confirm the changes in cell viability, production of reactive oxygen species, and MMP13 and BNIP3 gene expression levels. In addition, the radical scavenging ability of HPH was evaluated using an ABTS assay. Results: After treating the cells with the test substance for 72 hours, the cell viability increased by up to 28% in the HPH/lidocaine-treated group compared to the lidocaine-treated group. The level of reactive oxygen species, which was increased by lidocaine, was lower in the group treated with HPH/lidocaine. In addition, the expression levels of the MMP13 gene, which damages cartilage tissue, and the BNIP3 gene, which is involved in mitophagy, were also 21% and 69% lower, respectively, in the HPH/lidocaine-treated group than in the lidocainetreated group. Conclusion HPH may alleviate the side effects of an intra-articular injection of lidocaine by suppressing cell death, suppressing free radicals, and alleviating intracellular mitochondrial damage.

Background: Molecular cancer profiling may lead to appropriate trials for molecularly targeted therapies. Cell-free DNA (cfDNA) is a promising diagnostic and/or prognostic biomarker in gastric cancer (GC). We characterized somatic genomic alterations in cfDNA of patients with GC. Methods: Medical records and cfDNA data of 81 patients diagnosed as having GC were reviewed. Forty-nine and 32 patients were tested using the Oncomine Pan-Cancer CellFree Assay on the Ion Torrent platform and AlphaLiquid 100 kit on the Illumina platform, respectively. Results: Tier I or II alterations were detected in 64.2% (52/81) of patients. Biomarkers for potential targeted therapy were detected in 55.6% of patients (45/81), and clinical trials are underway. ERBB2 amplification is actionable and was detected in 4.9% of patients (4/81). Among biomarkers showing potential for possible targeted therapy, TP53 mutation (38.3%, 35 variants in 31 patients, 31/81) and FGFR2 amplification (6.2%, 5/81) were detected the most. Conclusions Next-generation sequencing of cfDNA is a promising technique for the molecular profiling of GC. Evidence suggests that cfDNA analysis can provide accurate and reliable information on somatic genomic alterations in patients with GC, potentially replacing tissue biopsy as a diagnostic and prognostic tool. Through cfDNA analysis for molecular profiling, it may be possible to translate the molecular classification into therapeutic targets and predictive biomarkers, leading to personalized treatment options for patients with GC in the future.

External quality assessment (EQA) trials for newborn screening tests were conducted twice in 2022 and 2023. These included tests for congenital hypothyroidism, adrenal hyperplasia, and galactosemia, as well as tandem mass spectrometry-based screenings for conditions such as phenylketonuria, maple syrup urine disease, homocystinuria. Each trial involved the analysis of six dried blood spot specimens for each test item across 15 laboratories.The mean, standard deviation, median, minimum and maximum values, and cut-offs were determined for each analyte in the newborn screening tests.The proportion of correct answers was 93%–100%. Additionally, EQA trials for the analyses of methylmalonic acid, vanillylmandelic acid, homovanillic acid, catecholamines, metanephrines, amino acids, and organic acids were performed using three specimens per trial. A well-designed EQA program, combined with continuous education, can help improve the performance of newborn screening and metabolite testing.

External quality assessment (EQA) trials for newborn screening tests were conducted twice in 2022 and 2023. These included tests for congenital hypothyroidism, adrenal hyperplasia, and galactosemia, as well as tandem mass spectrometry-based screenings for conditions such as phenylketonuria, maple syrup urine disease, homocystinuria. Each trial involved the analysis of six dried blood spot specimens for each test item across 15 laboratories.The mean, standard deviation, median, minimum and maximum values, and cut-offs were determined for each analyte in the newborn screening tests.The proportion of correct answers was 93%–100%. Additionally, EQA trials for the analyses of methylmalonic acid, vanillylmandelic acid, homovanillic acid, catecholamines, metanephrines, amino acids, and organic acids were performed using three specimens per trial. A well-designed EQA program, combined with continuous education, can help improve the performance of newborn screening and metabolite testing.

External quality assessment (EQA) trials for newborn screening tests were conducted twice in 2022 and 2023. These included tests for congenital hypothyroidism, adrenal hyperplasia, and galactosemia, as well as tandem mass spectrometry-based screenings for conditions such as phenylketonuria, maple syrup urine disease, homocystinuria. Each trial involved the analysis of six dried blood spot specimens for each test item across 15 laboratories.The mean, standard deviation, median, minimum and maximum values, and cut-offs were determined for each analyte in the newborn screening tests.The proportion of correct answers was 93%–100%. Additionally, EQA trials for the analyses of methylmalonic acid, vanillylmandelic acid, homovanillic acid, catecholamines, metanephrines, amino acids, and organic acids were performed using three specimens per trial. A well-designed EQA program, combined with continuous education, can help improve the performance of newborn screening and metabolite testing.

Pinitol (3-O-Methyl-D-chiro-inositol) has been reported to possess insulin-like effects and is known as one of the anti-diabetic agents to improve muscle, liver, and endothelial cells. However, the beneficial effects of pinitol on the skin are not well known.Here, we investigated whether pinitol had effects on human dermal fibroblasts (HDFs), and human dermal equivalents (HDEs) irradiated with ultraviolet A (UVA), which causes various damages including photodamage in the skin. We observed that pinitol enhanced wound healing in UVA-damaged HDFs. We also found that pinitol significantly antagonized the UVA-induced up-regulation of matrix metalloproteinase 1 (MMP1), and the UVA-induced down-regulation of collagen type I and tissue inhibitor of metalloproteinases 1 (TIMP1) in HDEs. Electron microscopy analysis also revealed that pinitol remarkably increased the number of collagen fibrils with regular banding patterns in the dermis of UVA-irradiated human skin equivalents. Pinitol significantly reversed the UVAinduced phosphorylation levels of ERK and JNK but not p38, suggesting that this regulation may be the mechanism underlying the pinitol-mediated effects on UVA-irradiated HDEs. We also observed that pinitol specifically increased Smad3 phosphorylation, which is representative of the TGF-β signaling pathway for collagen synthesis. These data suggest that pinitol exerts several beneficial effects on UVA-induced damaged skin and can be used as a therapeutic agent to improve skin-related diseases.

External quality assessment (EQA) trials for newborn screening tests were conducted twice in 2022 and 2023. These included tests for congenital hypothyroidism, adrenal hyperplasia, and galactosemia, as well as tandem mass spectrometry-based screenings for conditions such as phenylketonuria, maple syrup urine disease, homocystinuria. Each trial involved the analysis of six dried blood spot specimens for each test item across 15 laboratories.The mean, standard deviation, median, minimum and maximum values, and cut-offs were determined for each analyte in the newborn screening tests.The proportion of correct answers was 93%–100%. Additionally, EQA trials for the analyses of methylmalonic acid, vanillylmandelic acid, homovanillic acid, catecholamines, metanephrines, amino acids, and organic acids were performed using three specimens per trial. A well-designed EQA program, combined with continuous education, can help improve the performance of newborn screening and metabolite testing.