Objective:To explore the correlation between serum carbohydrate antigen 72-4 (CA72-4) level and pathological differentiation degree of gastric cancer, and to provide reference for early diagnosis, prognosis evaluation and efficacy monitoring of gastric cancer.Methods:A retrospective study was conducted on 136 patients with gastric cancer admitted to Zhejiang Provincial People′s Hospital from April 2022 to December 2024. According to postoperative pathological diagnosis, patients were divided into well-differentiated group ( n=9), moderately differentiated group ( n=36) and poorly/undifferentiated group ( n=91). Preoperative CA72-4 levels and clinical characteristics of patients were collected to analyze the relationship between differentiation degree and CA72-4 level, and to compare the changes of CA72-4 before and after surgery in gastric cancer patients with different differentiation degrees. Results:The preoperative CA72-4 level in the poorly/undifferentiated group was significantly higher than that in the well-differentiated group and moderately differentiated group (all P<0.001). Preoperative CA72-4 level in gastric cancer patients was weakly negatively correlated with differentiation degree ( R=-0.341). After surgery, the CA72-4 level in the poorly/undifferentiated group decreased significantly compared with that before surgery ( P=0.043), while the changes in the well-differentiated group and moderately differentiated group were not significant. Conclusions:There are significant differences in CA72-4 levels among gastric cancer groups with different differentiation degrees. Preoperative CA72-4, as a tumor marker, is of great significance for early diagnosis, prognosis evaluation and postoperative monitoring of gastric cancer. Especially in patients with poorly/undifferentiated gastric cancer, the CA72-4 level is relatively high, which can be used for auxiliary diagnosis and formulation of treatment plans.

OBJECTIVES: To propose a single repetition time (TR) quantitative magnetic susceptibility imaging method for the lumbar spine using bipolar readout gradient, and compare the quantitative magnetic susceptibility measurement using single TR and dual TR methods for the lumbar spine with different bone densities. METHODS: A translation correction method was proposed to correct spatial misalignment along the frequency encoding direction between positive and negative gradient readout images, and the phase difference between the images was eliminated using a phase correction method. The data of lumbar vertebrae L1-L5 were collected using single TR and dual TR methods from 6 normal individuals, 2 patients with osteopenia, and 2 patients with osteoporosis. The magnetic susceptibility map was reconstructed, the quantitative results of single TR before and after correction were compared with those of the dual TR method. RESULTS: The linear regression result of the lumbar spine magnetic susceptibility values obtained by the single TR method before calibration and the dual TR method is Y=0.64*X-11.61. The linear regression result of the lumbar spine magnetic susceptibility values corrected by the single TR method and the dual TR method is Y=1.03*X+0.25. The results of the corrected single TR method were highly consistent with those of the dual TR method, and the calibrated single TR method could effectively distinguish osteopenia and osteoporosis patients from normal individuals. CONCLUSIONS The calibrated single TR bipolar readout gradient method can generate artifact-free lumbar spine quantitative magnetic susceptibility distribution maps and reduce data acquisition time by 50%.
Humans ; Lumbar Vertebrae/pathology* ; Magnetic Resonance Imaging/methods* ; Female ; Middle Aged ; Male ; Osteoporosis/diagnosis* ; Adult ; Bone Density ; Aged ; Bone Diseases, Metabolic/diagnosis*

Objective·To investigate the expression of protein tyrosine phosphatase receptor type N(PTPRN)in lung adenocarcinoma and its potential molecular mechanisms in promoting lung adenocarcinoma metastasis.Methods·A highly bone-metastatic A549-BM cell line was established through multiple rounds of intracardiac injection.RNA sequencing(RNA-seq),combined with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,was performed to identify PTPRN as a key metastasis-related gene.Subsequently,The Cancer Genome Atlas(TCGA)database was utilized to evaluate PTPRN expression in patients with lung adenocarcinoma and its correlation with clinical prognosis.Co-expression analysis based on TCGA data was conducted to identify and analyze key genes co-expressed with PTPRN.Small interfering RNA(siRNA)targeting PTPRN(siPTPRN)was transfected into A549-BM cells,and Transwell assays were performed to assess its effects on cell migration and invasion.Western blotting was used to detect the expression of epithelial-mesenchymal transition(EMT)-related proteins and the activation of the PI3K-AKT signaling pathway.siPTPRN-transfected A549-BM cells were injected into a mouse model via intracardiac injection,and in vivo metastasis was assessed.Additionally,multiple database analyses were integrated to predict BCL6 as an upstream transcription factor of PTPRN,and siBCL6 transfection experiments were performed to validate the regulatory effect of BCL6 on PTPRN expression.Results·RNA-seq and GO/KEGG enrichment analyses demonstrated that PTPRN was significantly upregulated in highly metastatic A549-BM cells and enriched in metastasis-associated pathways,including the PI3K-AKT signaling pathway and extracellular matrix(ECM)-receptor interactions.Analysis of the TCGA database further confirmed that PTPRN was highly expressed in lung adenocarcinoma patients and significantly associated with poor prognosis.Co-expression analysis based on TCGA data,combined with GO/KEGG enrichment analyses,revealed that PTPRN-associated genes were mainly enriched in biological processes such as neural signaling,endocrine regulation,cell communication,and ECM-receptor interactions.In vitro experiments demonstrated that siPTPRN transfection significantly inhibited the migration and invasion of A549-BM cells,accompanied by downregulation of EMT-related proteins and reduced activation of the PI3K-AKT signaling pathway.In vivo experiments further showed that PTPRN knockdown markedly suppressed the metastatic potential of A549-BM cells,confirming its pro-metastatic role.Additionally,siBCL6 transfection experiments demonstrated that BCL6 knockdown upregulated PTPRN expression.Conclusion·PTPRN is highly expressed in lung adenocarcinoma tissues and promotes tumor cell migration and metastasis by enhancing EMT and activating the PI3K-AKT signaling pathway.High PTPRN expression is significantly correlated with poor prognosis in lung adenocarcinoma patients,while PTPRN enhances lung adenocarcinoma cell invasiveness and metastatic potential.BCL6 may act as an upstream transcriptional regulator of PTPRN,influencing its expression levels.

Objective To investigate the possible mechanism by which CID11210285hydrochloride(Wnt agonist 1,AMBMP,BML-284)regulates aluminum-induced neuronal ferroptosis through the Wnt/β-catenin pathway,providing a theoretical basis for fur-ther research on the mechanisms of aluminum-induced neuronal death.Methods Taking rat adrenal pheochromocytoma PC12 cells as the research object,determined exposure concentrations of Al(mal)3 and BML-284 via CCK-8 assay and divided into four groups:con-trol group,Al(mal)3group,BML-284group,and Al(mal)3+BML-284group.The contents of iron,glutathione(GSH),reactive oxy-gen species(ROS),and malondialdehyde(MDA)in PC12 cells were detected by using the kit.The protein expression of glutathione peroxidase 4(GPX4),solute carrier family 7member 11(SLC7A11),glycogen synthase kinase 3β(GSK3β),β-catenin,and tran-scription factor 4(TCF4)was analyzed by Western blot.The mRNA expression of GPX4 and SLC7A11 was determined by real-time flu-orescence quantitative polymerase chain reaction(RT-qPCR).Results Compared with the control group,the iron ion concentration in PC12 cells of the Al(mal)3group increased,while the expression of GPX4 protein decreased.Compared with the Al(mal)3group,the iron ion concentration in PC12 cells of the Al(mal)3+BML-284 group increased(P＜0.05),and the expression of GPX4 protein and mR-NA increased(P＜0.05).Conclusion BML-284 activates the Wnt/β-catenin pathway by promoting the stability and intranuclear accumulation of β-catenin and enhancing the formation of the β-catenin/TCF complex,in which TCF4 serves as a key transcription fac-tor,and the β-catenin/TCF4 complex directly binds to GPX4,which effectively alleviates the Al(mal)3-induced ferroptosis.

Objective·To investigate the expression level of O-GlcNAc transferase(OGT)in non-small cell lung cancer(NSCLC)and its impact on lung cancer proliferation,as well as to explore the underlying mechanisms.Methods·The expression of OGT in NSCLC tumors and adjacent normal tissues was detected by immunohistochemistry(IHC).The dataset(GSE31210)from the GEO database was analyzed to assess the correlation between OGT expression and NSCLC patient prognosis.siRNA transfection was performed to knock down OGT expression in H460 and H1299 cells,followed by total RNA extraction and transcriptome sequencing.Pathway enrichment analysis was conducted on differentially downregulated genes in the knockdown group compared with the control group,and Western blotting was used to validate the enrichment results.The effects of OGT knockdown on cell proliferation and colony formation in H460 and H1299 cells were evaluated using the cell counting kit-8(CCK-8)assay and colony formation assay,respectively.The impact of overexpressing downstream genes was also examined.Stable OGT-knockdown cell lines were generated using shRNA and subcutaneously inoculated into nude mice to monitor tumor growth.Results·IHC revealed that OGT expression was significantly upregulated in NSCLC tumor tissues compared to adjacent normal tissues.Patients with high OGT expression exhibited shorter survival times and poorer prognoses than those with low expression.Transcriptome sequencing demonstrated that genes downregulated after OGT knockdown were primarily enriched in the mitogen-activated protein kinase(MAPK)signaling pathway.Western blotting showed that total extracellular regulated protein kinase 1/2(ERK1/2)levels remained unchanged in H460 and H1299 cells after OGT knockdown,while phosphorylated ERK1/2(p-ERK1/2)and its downstream proto-oncogene JUNB protein were markedly reduced.Suppression of OGT expression attenuated the proliferation rate and colony formation capacity of H460 and H1299 cells,whereas JUNB overexpression rescued the proliferation defects induced by OGT knockdown.Notably,H460 cells with stable OGT knockdown formed significantly smaller tumors in nude mice.Conclusion·OGT is highly expressed in NSCLC and correlates with poor prognosis.Knockdown of OGT inhibits NSCLC cell proliferation and clonogenicity in vitro,and tumor growth in vivo.Mechanistically,OGT appears to promote NSCLC progression by activating the ERK/JUNB signaling axis.

Objective·To investigate the expression of protein tyrosine phosphatase receptor type N(PTPRN)in lung adenocarcinoma and its potential molecular mechanisms in promoting lung adenocarcinoma metastasis.Methods·A highly bone-metastatic A549-BM cell line was established through multiple rounds of intracardiac injection.RNA sequencing(RNA-seq),combined with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,was performed to identify PTPRN as a key metastasis-related gene.Subsequently,The Cancer Genome Atlas(TCGA)database was utilized to evaluate PTPRN expression in patients with lung adenocarcinoma and its correlation with clinical prognosis.Co-expression analysis based on TCGA data was conducted to identify and analyze key genes co-expressed with PTPRN.Small interfering RNA(siRNA)targeting PTPRN(siPTPRN)was transfected into A549-BM cells,and Transwell assays were performed to assess its effects on cell migration and invasion.Western blotting was used to detect the expression of epithelial-mesenchymal transition(EMT)-related proteins and the activation of the PI3K-AKT signaling pathway.siPTPRN-transfected A549-BM cells were injected into a mouse model via intracardiac injection,and in vivo metastasis was assessed.Additionally,multiple database analyses were integrated to predict BCL6 as an upstream transcription factor of PTPRN,and siBCL6 transfection experiments were performed to validate the regulatory effect of BCL6 on PTPRN expression.Results·RNA-seq and GO/KEGG enrichment analyses demonstrated that PTPRN was significantly upregulated in highly metastatic A549-BM cells and enriched in metastasis-associated pathways,including the PI3K-AKT signaling pathway and extracellular matrix(ECM)-receptor interactions.Analysis of the TCGA database further confirmed that PTPRN was highly expressed in lung adenocarcinoma patients and significantly associated with poor prognosis.Co-expression analysis based on TCGA data,combined with GO/KEGG enrichment analyses,revealed that PTPRN-associated genes were mainly enriched in biological processes such as neural signaling,endocrine regulation,cell communication,and ECM-receptor interactions.In vitro experiments demonstrated that siPTPRN transfection significantly inhibited the migration and invasion of A549-BM cells,accompanied by downregulation of EMT-related proteins and reduced activation of the PI3K-AKT signaling pathway.In vivo experiments further showed that PTPRN knockdown markedly suppressed the metastatic potential of A549-BM cells,confirming its pro-metastatic role.Additionally,siBCL6 transfection experiments demonstrated that BCL6 knockdown upregulated PTPRN expression.Conclusion·PTPRN is highly expressed in lung adenocarcinoma tissues and promotes tumor cell migration and metastasis by enhancing EMT and activating the PI3K-AKT signaling pathway.High PTPRN expression is significantly correlated with poor prognosis in lung adenocarcinoma patients,while PTPRN enhances lung adenocarcinoma cell invasiveness and metastatic potential.BCL6 may act as an upstream transcriptional regulator of PTPRN,influencing its expression levels.

Objective·To investigate the expression level of O-GlcNAc transferase(OGT)in non-small cell lung cancer(NSCLC)and its impact on lung cancer proliferation,as well as to explore the underlying mechanisms.Methods·The expression of OGT in NSCLC tumors and adjacent normal tissues was detected by immunohistochemistry(IHC).The dataset(GSE31210)from the GEO database was analyzed to assess the correlation between OGT expression and NSCLC patient prognosis.siRNA transfection was performed to knock down OGT expression in H460 and H1299 cells,followed by total RNA extraction and transcriptome sequencing.Pathway enrichment analysis was conducted on differentially downregulated genes in the knockdown group compared with the control group,and Western blotting was used to validate the enrichment results.The effects of OGT knockdown on cell proliferation and colony formation in H460 and H1299 cells were evaluated using the cell counting kit-8(CCK-8)assay and colony formation assay,respectively.The impact of overexpressing downstream genes was also examined.Stable OGT-knockdown cell lines were generated using shRNA and subcutaneously inoculated into nude mice to monitor tumor growth.Results·IHC revealed that OGT expression was significantly upregulated in NSCLC tumor tissues compared to adjacent normal tissues.Patients with high OGT expression exhibited shorter survival times and poorer prognoses than those with low expression.Transcriptome sequencing demonstrated that genes downregulated after OGT knockdown were primarily enriched in the mitogen-activated protein kinase(MAPK)signaling pathway.Western blotting showed that total extracellular regulated protein kinase 1/2(ERK1/2)levels remained unchanged in H460 and H1299 cells after OGT knockdown,while phosphorylated ERK1/2(p-ERK1/2)and its downstream proto-oncogene JUNB protein were markedly reduced.Suppression of OGT expression attenuated the proliferation rate and colony formation capacity of H460 and H1299 cells,whereas JUNB overexpression rescued the proliferation defects induced by OGT knockdown.Notably,H460 cells with stable OGT knockdown formed significantly smaller tumors in nude mice.Conclusion·OGT is highly expressed in NSCLC and correlates with poor prognosis.Knockdown of OGT inhibits NSCLC cell proliferation and clonogenicity in vitro,and tumor growth in vivo.Mechanistically,OGT appears to promote NSCLC progression by activating the ERK/JUNB signaling axis.

Objective To investigate the possible mechanism by which CID11210285hydrochloride(Wnt agonist 1,AMBMP,BML-284)regulates aluminum-induced neuronal ferroptosis through the Wnt/β-catenin pathway,providing a theoretical basis for fur-ther research on the mechanisms of aluminum-induced neuronal death.Methods Taking rat adrenal pheochromocytoma PC12 cells as the research object,determined exposure concentrations of Al(mal)3 and BML-284 via CCK-8 assay and divided into four groups:con-trol group,Al(mal)3group,BML-284group,and Al(mal)3+BML-284group.The contents of iron,glutathione(GSH),reactive oxy-gen species(ROS),and malondialdehyde(MDA)in PC12 cells were detected by using the kit.The protein expression of glutathione peroxidase 4(GPX4),solute carrier family 7member 11(SLC7A11),glycogen synthase kinase 3β(GSK3β),β-catenin,and tran-scription factor 4(TCF4)was analyzed by Western blot.The mRNA expression of GPX4 and SLC7A11 was determined by real-time flu-orescence quantitative polymerase chain reaction(RT-qPCR).Results Compared with the control group,the iron ion concentration in PC12 cells of the Al(mal)3group increased,while the expression of GPX4 protein decreased.Compared with the Al(mal)3group,the iron ion concentration in PC12 cells of the Al(mal)3+BML-284 group increased(P＜0.05),and the expression of GPX4 protein and mR-NA increased(P＜0.05).Conclusion BML-284 activates the Wnt/β-catenin pathway by promoting the stability and intranuclear accumulation of β-catenin and enhancing the formation of the β-catenin/TCF complex,in which TCF4 serves as a key transcription fac-tor,and the β-catenin/TCF4 complex directly binds to GPX4,which effectively alleviates the Al(mal)3-induced ferroptosis.

Objective:To explore the correlation between serum carbohydrate antigen 72-4 (CA72-4) level and pathological differentiation degree of gastric cancer, and to provide reference for early diagnosis, prognosis evaluation and efficacy monitoring of gastric cancer.Methods:A retrospective study was conducted on 136 patients with gastric cancer admitted to Zhejiang Provincial People′s Hospital from April 2022 to December 2024. According to postoperative pathological diagnosis, patients were divided into well-differentiated group ( n=9), moderately differentiated group ( n=36) and poorly/undifferentiated group ( n=91). Preoperative CA72-4 levels and clinical characteristics of patients were collected to analyze the relationship between differentiation degree and CA72-4 level, and to compare the changes of CA72-4 before and after surgery in gastric cancer patients with different differentiation degrees. Results:The preoperative CA72-4 level in the poorly/undifferentiated group was significantly higher than that in the well-differentiated group and moderately differentiated group (all P<0.001). Preoperative CA72-4 level in gastric cancer patients was weakly negatively correlated with differentiation degree ( R=-0.341). After surgery, the CA72-4 level in the poorly/undifferentiated group decreased significantly compared with that before surgery ( P=0.043), while the changes in the well-differentiated group and moderately differentiated group were not significant. Conclusions:There are significant differences in CA72-4 levels among gastric cancer groups with different differentiation degrees. Preoperative CA72-4, as a tumor marker, is of great significance for early diagnosis, prognosis evaluation and postoperative monitoring of gastric cancer. Especially in patients with poorly/undifferentiated gastric cancer, the CA72-4 level is relatively high, which can be used for auxiliary diagnosis and formulation of treatment plans.

Objective To design and test a device which is capable of accurately measuring and dynamically adjusting the axial pressure at the fracture end in real-time.Methods Upon completion of the design,the pressure measurement and adjustment device was implemented in a canine tibial fracture external fixation model.A pressure sensor was mounted at the fracture end,and the displayed values of the pressure sensor were used as the standard for comparison.The relationship between the displayed values of the measurement and adjustment device and the pressure sensor under identical conditions was examined.Results The device was utilized in external fixation models of tibial fractures in five beagles.A linear correlation was observed between the displayed values of the device and the pressure sensor at the fracture end.The measurement values from the device could be transformed into fracture end pressure through the application of coefficients,thereby facilitating accurate measurement and dynamic adjustment of the fracture end pressure.Conclusion The pressure measurement and adjustment device at the fracture end is easy to operate,enabling precise measurement and dynamic regulation of the pressure at the fracture end.It is well-suited for animal experiments aimed at investigating the impact of axial compression on fracture healing,demonstrating promising potential for experimental applications.