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The purpose of this study was to assess the relationship between 25-hydroxyvitamin D (25(OH)D), urinary iodine concentration (UIC), and type 2 diabetes mellitus (T2DM) risk and complications and to establish a model to predict T2DM in the general population. A total of 567 adults (389 T2DM patients and 178 controls) were enrolled, and the levels of 25(OH)D, iodine, and blood biochemical parameters were measured. Pearson’s correlation analysis showed an inverse correlation between 25(OH)D level, UIC, and T2DM risk. Low 25(OH)D level was a risk factor for developing T2DM (OR, 0.81; 95% CI, 1.90–2.63; P = 0.043) after adjustment for multiple risk factors. 25(OH)D level and UIC were inversely correlated with short-term and long-term glucose levels. 25(OH)D deficiency was also associated with a high incidence of T2DM complicated with thyroid dysfunction. A prediction model based on 25(OH)D, iodine status, and other risk factors was established and recommended to screen high-risk T2DM in the general population and provide early screening and timely treatment for them.

Accumulating evidence supports the notion that S100A16 exhibits differential expression in many human cancers, affecting cellular functions associated with tumorigenesis through various signaling pathways. While extensive research has been conducted on S100A16 in specific cancer types, a comprehensive evaluation of its role across diverse cancers remains lacking. To explore the prognostic significance, drug sensitivity, and immunomodulatory roles of S100A16, a thorough analysis was conducted at a pan-cancer level using multiple databases. Our findings revealed high expression of S100A16 RNA in various human cancers. Importantly, this elevated expression was linked to disease prognosis and drug sensitivity across a spectrum of cancers. Genetic alterations in S100A16 were characterized across multiple cancer types, and a confirmed correlation was observed in the prognosis of skin cutaneous melanoma (SKCM). Furthermore, our study demonstrated a significant association between S100A16 expression and the infiltrating levels of diverse cell types in the tumor microenvironment (TME), suggesting its potential as a prognosis predictor for immunotherapy. Novel collections of miRNAs, such as has-miR-423-5p, has-miR-769-5p, has-miR-151a-3p, and has-miR-550a-5p, targeting S100A16 at a pan-cancer level were predicted through various databases. These findings contribute to a comprehensive understanding the role of S100A16 in prognosis prediction, chemotherapy, and immunotherapy, providing valuable insights for identifying novel targets in cancer treatment., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The genetic heterogeneity of non-small cell lung cancer (NSCLC) may impact clinical response and outcomes to targeted therapies. In second-line osimertinib treatment for NSCLC, real-world data on genetic biomarkers for treatment efficacy and prognosis remain incomplete. This real-world study involved 68 NSCLC patients receiving first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). All of these patients developed resistance, and 49 of them subsequently underwent second-line osimertinib treatment. A 639-gene DNA panel was employed to assess the impact of molecular alterations on treatment efficacy, clinical outcomes and resistance. The findings showed that the median progression-free survival (PFS) for second-line osimertinib therapy was 13.3 months. Genes alterations such as P21 (RAC1) activated kinase 5 ( PAK5 ), RNA binding motif protein 10 ( RBM10 ), and EPH receptor A3 ( EPHA3 ) mutations were associated with significantly shorter PFS in osimertinib therapy. At multivariate analysis, they were all independent risk predictors of shorter PFS. Additionally, the median overall survival (OS) for osimertinib was 26.2 months. Glutamate ionotropic receptor NMDA type subunit 2A ( GRIN2A ), hepatocyte growth factor ( HGF ), and RBM10 mutations were significantly associated with poorer OS in osimertinib treatment. The multivariate analysis demonstrated that only RBM10 mutation emerged as an independent risk predictor of shorter OS. In vitro experiments showed that RBM10 mutations could promote the proliferation and migration ability of NSCLC cells and reduced cell apoptosis. The resistance mechanisms to osimertinib were heterogeneous. Histone cluster 1 H2B family member D ( HIST1H2BD ) acted as a novel resistance mechanism to osimertinib. Previously unreported HIST1H2BD mutations (p.K25Q and p.E36D) were detected in the NSCLC tissues. In vitro experiments confirmed that HIST1H2BD mutations led to resistance to osimertinib. In summary, we demonstrate that genetic biomarkers, such as PAK5, RBM10 , and EPHA3 , are independent predictors of PFS in second-line osimertinib treatment, with RBM10 emerging as an independent predictor of OS. Additionally, HIST1H2BD represents a novel resistance mutation to osimertinib. All of these findings offer valuable insights for making personalized treatment strategies for NSCLC patients., Competing Interests: WYX, YYH and LD were employed by company Singlera Genomics (Shanghai) Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (AJCR Copyright © 2024.)

Nonsense-mediated mRNA decay (NMD) is a widespread quality control mechanism in eukaryotic cells. It can recognize and degrade aberrant transcripts harbouring a premature translational termination codon (PTC), and thereby prevent the production of C-terminally truncated proteins which might be deleterious. Approximately, 30% of human genetic diseases are caused by transcripts containing PTCs. These transcripts are potential targets of NMD. As for monogenic diseases, NMD has effects on the phenotype or mode of inheritance. Here, we explain the mechanism of this surveillance pathway, and take several neuromuscular disorders as examples to discuss its influence for human monogenic diseases. The deeper understanding for NMD will shed light on the nosogenesis and therapies of monogenic diseases.

Objective: To study the potentiality of osteanagenesis of the hematomas formed around the fractures and that of the marrow stroma cells, evaluate the effect of the combined trans-plantation of the hematoma and the marrow stroma cells, to explore a new method to accelerate the union of fracture., Methods: The bone defect models were made on the tibias of the New-Zealand's rabbits. The hematomas formed around the fracture were taken out 3 days latter after the operation, the marrow stroma cells were abstracted from the femoral marrow simultaneously. And then the mixture of the hematoma and the marrow stroma cells were transplanted to the defects of the tibias in the experiment group, and the hematoma transplanted simply to the same place in the control group. The radio-graph and the histological observation of the osteotylus were carried out regularly post-operation., Results: 1) There was a significant difference in osteotylus quantity between the two groups: more osteotylus and obvious periosteal proliferation were found in the experiment group than that in the control group which accepted the transplantation of the hematomas alone. 2) There was a significant difference in osteoblast number between the two groups: more sclerotomal-like cells were observed under the microscope in the experiment group than that in the control group., Conclusion: Marrow stroma cells have great potentiality of osteoanagenesis. The result of combined transplantation of the marrow stroma cells and the hematomas is more effective than that of simple transplantation of the bone hematoma.