Background: Intestinal-type gastric adenocarcinoma, representing 95 % of gastric malignancies, originates from the malignant transformation of gastric gland cells. Despite its prevalence, existing methods for prognosis evaluation of this cancer subtype are inadequate. This study aims to enhance patient-specific prognosis evaluation by analyzing the clinicopathological characteristics and prognostic risk factors of intestinal-type gastric adenocarcinoma patients using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI). Methods: We extracted clinical data for patients diagnosed with intestinal-type gastric adenocarcinoma between 2010 and 2015 from the SEER database, selecting 257 cases based on predefined inclusion and exclusion criteria. Independent risk factors for overall survival (OS) and cancer-specific survival (CSS) were identified using a Cox regression model. A nomogram model for predicting OS or CSS was developed from the Cox risk regression analysis and validated through the consistency index (C-index), ROC curve, and calibration curve. Results: Age, primary tumor resection, chemotherapy, lymph node metastasis, and tumor size were identified as independent prognostic factors for OS and CSS (P < 0.05). The nomogram model, constructed from these indicators, demonstrated superior predictive consistency for OS and CSS compared to the AJCC-TNM staging system. ROC curve analysis confirmed the model's higher accuracy, and calibration curve analysis indicated good agreement between the nomogram's predictions and actual observed outcomes. Conclusion: The nomogram model derived from SEER database analyses accurately predicts OS and CSS for patients with intestinal-type gastric adenocarcinoma. This model promises to facilitate more tailored treatments in clinical practice.
Multiple regulatory mechanisms are in place to ensure the normal processes of bone metabolism, encompassing both bone formation and absorption. This study has identified chaperone-mediated autophagy (CMA) as a critical regulator that safeguards bone formation from the detrimental effects of excessive inflammation. By silencing LAMP2A or HSCA8, we observed a hindrance in the osteoblast differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. To further elucidate the role of LAMP2A, we generated LAMP2A gene knockdown and overexpression of mouse BMSCs (mBMSCs) using adenovirus. Our results showed that LAMP2A knockdown led to a decrease in osteogenic-specific proteins, while LAMP2A overexpression favored the osteogenesis of mBMSCs. Notably, active-ß-catenin levels were upregulated by LAMP2A overexpression. Furthermore, we found that LAMP2A overexpression effectively protected the osteogenesis of mBMSCs from TNF-α, through the PI3K/AKT/GSK3ß/ß-catenin pathway. Additionally, LAMP2A overexpression significantly inhibited osteoclast hyperactivity induced by TNF-α. Finally, in a murine bone defect model, we demonstrated that controlled release of LAMP2A overexpression adenovirus by alginate sodium capsule efficiently protected bone healing from inflammation, as confirmed by imaging and histological analyses. Collectively, our findings suggest that enhancing CMA has the potential to safeguard bone formation while mitigating hyperactivity in bone absorption.
Chaperone-Mediated Autophagy , Glycogen Synthase Kinase 3 beta , Inflammation , Lysosomal-Associated Membrane Protein 2 , Mesenchymal Stem Cells , Osteogenesis , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , beta Catenin , Animals , Osteogenesis/physiology , Glycogen Synthase Kinase 3 beta/metabolism , Glycogen Synthase Kinase 3 beta/genetics , Proto-Oncogene Proteins c-akt/metabolism , Mice , Phosphatidylinositol 3-Kinases/metabolism , beta Catenin/metabolism , Humans , Mesenchymal Stem Cells/metabolism , Inflammation/metabolism , Lysosomal-Associated Membrane Protein 2/metabolism , Lysosomal-Associated Membrane Protein 2/genetics , Signal Transduction , Male , Mice, Inbred C57BL , Osteoblasts/metabolism , Cell Differentiation , Osteoclasts/metabolism
OBJECTIVES: In clinical practice, the majority of α-thalassaemia cases arise from deletions of the α-globin genes. However, a subset of cases is attributed to rare haemoglobin variants, which can manifest with borderline or normal screening results, potentially leading to missed diagnoses in clinical practice. METHODS: Blood samples were collected from family members and underwent haematological, DNA and RNA analysis. RESULTS: The five-month-old proband presented a haematological phenotype consistent with Hb H disease. The mother's haematology profile was consistent with an α-thalassaemia carrier, while the father exhibited a borderline reduction in MCV and MCH. MALDI-TOF identified an abnormal α-chain in the proband. DNA analysis revealed a novel α-globin variant (HBA2:c.175C>A, α58His>Asn, Hb DG-Nancheng) affecting the distal histidine in the family. The father and the mother had α-genotype of --SEA/αα and αDG-Nanchengα/αα, respectively; while the proband inherited both mutant alleles (--SEA/αDG-Nanchengα). Sequencing of cDNA from HBA2 gene identified an equal ratio of normal and mutant alleles. CONCLUSION: This rare case highlighted the importance of identifying rare haemoglobin variant during prenatal screening. The clinical and genetic data provides useful information on the pathogenicity of this variant and further insight into the role of distal histidine residue of α-globin.
Hemoglobins, Abnormal , alpha-Thalassemia , Female , Humans , Infant , Pregnancy , alpha-Globins/genetics , alpha-Thalassemia/diagnosis , alpha-Thalassemia/genetics , China , Hemoglobins, Abnormal/genetics , Histidine/genetics , Mutation
