To address the constrains imposed by insufficient hydrogen peroxide (H2O2) and high glutathione (GSH) expression in tumor cells on the efficacy of chemodynamic therapy (CDT), zeolitic imidazolate framework-8 (ZIF-8) loaded with disulfiram (DSF) and 3-amino-1,2,4-triazole (3-AT) was synthesized via a one-pot approach. Subsequently, hyaluronic acid (HA)-modified cupric peroxide (CuO2) was in-situ grown on its surface through biomineralization to construct a multifunctional copper-based nanozyme ADZCH (3-AT/DSF@ZIF-8@CuO2-HA). This nanoplatform disrupts the intratumoral H2O2 homeostasis, depletes GSH, and synchronously delivers DSF and Cu2+ via cascade catalysis, thereby enhancing CDT and sensitizing tumors to DSF-based chemotherapy. The results of physicochemical characterization indicated that ADZCH presented a uniform core-shell structure with favorable dispersibility. Its particle size and Zeta potential were 196.5 nm and −19.5 mV, respectively. It possessed a microporous structure with a specific surface area of 81.8600 m2/g, and demonstrated efficient loading capacity for DSF and 3-AT, achieving drug loading efficiencies of 5.91% and 45.07%, respectively. Moreover, ADZCH can continuously and slowly release drugs in an acidic environment and maintain good stability under diverse physiological conditions. In vitro functional assays verified that ADZCH catalytically generated H2O2 and hydroxyl radicals while concurrently depleting GSH in a concentration- and incubation time-dependent manner. Cellular uptake experiments showed that HA modification significantly improved the uptake of nanoparticles by 4T1 cells. Cytotoxicity tests showed that 80 μg/mL ADZCH had a significant cytotoxic effect on 4T1 cells but no significant toxicity on L929 cells. DCFH-DA probe detection indicated that ADZCH could significantly induce intracellular reactive oxygen species (ROS) generation, thereby enhancing CDT efficacy. Live/dead staining experiments showed that ADZCH efficiently induced apoptosis, with the proportion of dead cells reaching 94.74%, demonstrating its promising potential for anti-tumor applications.This study provides new research ideas and experimental basis for overcoming the tumor microenvironment barrier and enhancing the anti-tumor effect of CDT combined with chemotherapy.

Objective·To investigate the changes in transcriptome and chromatin accessibility during the differentiation of human embryonic stem cells(hESCs)into neural progenitor cells(NPCs)using in vitro differentiation models and high-throughput multi-omics sequencing technologies.Methods·hESCs were first induced to differentiate into NPCs in vitro using the embryoid body formation method,and cells at both stages were collected.The cell phenotypes were identified by reverse transcription-quantitative real-time PCR(RT-qPCR)and immunofluorescence(IF)staining.Transcriptome sequencing(RNA-seq)was conducted to detect and analyze the differentially expressed genes(DEGs)between hESCs and NPCs.The assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)was employed to assess chromatin accessibility changes between hESCs and NPCs.Motif enrichment analysis was performed on differentially accessible chromatin regions to discover potential regulatory transcription factors.Finally,an integrated analysis of RNA-seq and ATAC-seq data and the protein-protein interaction(PPI)network were performed to identify key genes and regulatory pathways involved in the early stages of neural differentiation in vitro.Results·Both RT-qPCR and IF results indicated that the expression levels of pluripotency markers(NANOG and POU5F1)were high at the hESC stage but significantly decreased at the NPC stage,while early neural differentiation markers(PAX6,SOX1,and NES)were minimally expressed at the hESC stage but markedly upregulated at the NPC stage.RNA-seq analysis revealed that compared to the hESC stage,there were 5 597 genes upregulated and 3 654 genes downregulated at the NPC stage.Gene function enrichment analysis showed that the upregulated genes at the NPC stage were enriched in the functions related to neural development.ATAC-seq analysis demonstrated a total of 27 491 genomic regions had significant changes in chromatin accessibility during the differentiation from hESC to NPC,with 12 381 regions showing increased accessibility and 15 110 regions showing decreased accessibility.Motif enrichment analysis revealed that transcription factor genes such as DLX1 and LHX2 might play an important role in the differentiation process from hESCs into NPCs.Integrated analysis of RNA-seq and ATAC-seq data revealed that overlapping genes with high expression at the NPC stage were mainly enriched in axon guidance,forebrain development,and neuron migration.After neural differentiation,the expression levels of CTNND2 and LHX2 genes increased,and the chromatin accessibility of related genomic regions also increased.PPI network analysis indentified candidate downstream genes including PRKACA,CDH2,and ERBB4.Conclusion·The in vitro differentiation model of hESCs combined with high-throughput multi-omics sequencing technologies can be used to depict the changes in transcriptome and chromatin accessibility during the differentiation of hESCs into NPCs.In this process,the expression levels of genes related to axon guidance,forebrain development,and neuronal migration pathways increase and related chromatin accessibility is enhanced.

Objective To explore the feasibility of spectral CT material decomposition technique Ca(Iodine)for opportunistic osteoporo-sis screening in enhanced scanning.Methods A total of 314 patients who underwent abdominal enhancement were selected.They were divided into group A and group B according to gender,and the groups were divided into three subgroups according to age(18-45 years,46-60 years,>60 years).The bone mineral density(BMD)values of L1-L3 vertebral were measured in the unenhanced images using quan-titative computed tomography(QCT)software,and Ca(Iodine)values were measured on three enhancement phases Ca(Iodine)based substance images.Pearson correlation analysis was performed between iodine intake and Ca(Iodine)values in three enhancement phases,Ca(Iodine)values and quantitative computed tomography bone mineral density(BMDQCT),and the diagnostic efficacy was analyzed.Results There was no significant difference in the Ca(Iodine)values of L1-L3 vertebral in three enhancement phases(F=0.001-0.018,P>0.05);there was no correlation between the Ca(Iodine)values of L1-L3 vertebral in three enhancement phases and iodine intake(r=0.073-0.105,P>0.05).Six groups of measured Ca(Iodine)values and BMDQCT both had a strong positive correlation(r=0.901-0.954,P<0.05).The Ca(Iodine)cutoff values for the diagnosis of osteoporosis and osteopenia were 830.41(2 mg/cm3)and 849.32(2 mg/cm3)respectively,with corresponding area under the curve(AUC)of 0.969[95%confidence interval(CI)0.943-0.985]and 0.973(95%CI 0.944-0.989),respectively.There were statistically significant differences in Ca(Iodine)values and BMDQCT in the>60 years age group between different genders(t=3.081-3.091,P<0.05).Conclusion Spectral CT material decomposition technique can be used for oppor-tunistic osteoporosis screening in enhanced scanning,with good diagnostic performance,which provides a new perspective for the clin-ical diagnosis of osteoporosis.

Objective·To investigate the changes in transcriptome and chromatin accessibility during the differentiation of human embryonic stem cells(hESCs)into neural progenitor cells(NPCs)using in vitro differentiation models and high-throughput multi-omics sequencing technologies.Methods·hESCs were first induced to differentiate into NPCs in vitro using the embryoid body formation method,and cells at both stages were collected.The cell phenotypes were identified by reverse transcription-quantitative real-time PCR(RT-qPCR)and immunofluorescence(IF)staining.Transcriptome sequencing(RNA-seq)was conducted to detect and analyze the differentially expressed genes(DEGs)between hESCs and NPCs.The assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)was employed to assess chromatin accessibility changes between hESCs and NPCs.Motif enrichment analysis was performed on differentially accessible chromatin regions to discover potential regulatory transcription factors.Finally,an integrated analysis of RNA-seq and ATAC-seq data and the protein-protein interaction(PPI)network were performed to identify key genes and regulatory pathways involved in the early stages of neural differentiation in vitro.Results·Both RT-qPCR and IF results indicated that the expression levels of pluripotency markers(NANOG and POU5F1)were high at the hESC stage but significantly decreased at the NPC stage,while early neural differentiation markers(PAX6,SOX1,and NES)were minimally expressed at the hESC stage but markedly upregulated at the NPC stage.RNA-seq analysis revealed that compared to the hESC stage,there were 5 597 genes upregulated and 3 654 genes downregulated at the NPC stage.Gene function enrichment analysis showed that the upregulated genes at the NPC stage were enriched in the functions related to neural development.ATAC-seq analysis demonstrated a total of 27 491 genomic regions had significant changes in chromatin accessibility during the differentiation from hESC to NPC,with 12 381 regions showing increased accessibility and 15 110 regions showing decreased accessibility.Motif enrichment analysis revealed that transcription factor genes such as DLX1 and LHX2 might play an important role in the differentiation process from hESCs into NPCs.Integrated analysis of RNA-seq and ATAC-seq data revealed that overlapping genes with high expression at the NPC stage were mainly enriched in axon guidance,forebrain development,and neuron migration.After neural differentiation,the expression levels of CTNND2 and LHX2 genes increased,and the chromatin accessibility of related genomic regions also increased.PPI network analysis indentified candidate downstream genes including PRKACA,CDH2,and ERBB4.Conclusion·The in vitro differentiation model of hESCs combined with high-throughput multi-omics sequencing technologies can be used to depict the changes in transcriptome and chromatin accessibility during the differentiation of hESCs into NPCs.In this process,the expression levels of genes related to axon guidance,forebrain development,and neuronal migration pathways increase and related chromatin accessibility is enhanced.

Objective To develop an automated bone mineral density(BMD)assessment model based on proximal femur images from abdomen-pelvic CT scans and to analyze its application value in opportunistic osteoporosis(OP)screening.Methods A retrospective selection was conducted on 351 patients who underwent abdomen-pelvic plain CT examination.The patients were randomly divided into training set(n=245)and test set(n=106)in a ratio of 7∶3.All images were transferred to a quantitative computed tomography(QCT)post-processing workstation to measure the BMD of the left proximal femur.According to the QCT BMD T-score,the patients were divided into osteoporosis(T-score-2.5),osteopenia(-2.5＜T-score＜-1)and normal bone density(T-score≥-1).The left proximal femur was dissected using an automatic segmentation model,and two three-class BMD assessment radiomics models were constructed using random forest(RF)and logistic regression(LR)classifiers,respectively.The receiver operating characteristic(ROC)curves were generated,and the area under the curve(AUC),sensitivity,specificity and other metrics were calculated to evaluate the diagnostic performance of the two models.The DeLong test was used to compare differences between the models.Results In the test set,the AUC of the RF and LR models for identifying osteoporosis were 0.953 and 0.954,respectively.The AUC for identifying osteopenia were 0.894 and 0.870,and the AUC for identifying normal bone density were 0.975 and 0.982,respectively.The comparison of model performance showed no statistically significant differences between the RF and LR models in identifying the three bone states in both the training and test sets(P＞0.05).Conclusion Both the RF and LR radiomics models,constructed based on abdomen-pelvic plain CT scans,can be used for opportunistic BMD screening with high diagnostic efficiency.

Objective To explore the feasibility of constructing a three-classification bone status screening radiomics model on chest CT images.Methods A total of 371 patients who underwent both chest and abdominal plain CT examinations were retrospec-tively selected and randomly divided into training set(296 cases)and test set(75 cases)in a ratio of 8︰2.Additionally,110 patients were included as external validation set using the same criteria.The 120 kVp abdominal images were transmitted to a quantitative compu-ted tomography(QCT)post-processing workstation to measure the bone mineral density(BMD)of the L1-L2 vertebral bodies.Patients were classified into osteoporosis(OP)group(BMD<80 mg/cm3),osteopenia group(80 mg/cm3≤BMD≤120 mg/cm3)and normal bone mass group(BMD>120 mg/cm3)based on QCT BMD results.The automatic segmentation model was used to segment T10-T12 vertebral trabecular bone on chest CT images and the radiomics models based on random forest(RF)and logistic regres-sion(LR)was established to evaluate BMD,enabling it to simultaneously distinguish OP,osteopenia,and normal bone mass.The diag-nostic performance of the two models were evaluated using metrics such as the area under the curve(AUC),sensitivity and specificity.The DeLong test was used to compare the differences between the two models.Results In the test set,the AUC for differentiating normal bone mass were 0.948 and 0.877 for the RF and LR models,respectively;the AUC for differentiating OP were 0.942 and 0.836,respectively;and the AUC for differentiating osteopenia were 0.871 and 0.688,respectively.The performance comparison results of the models showed that there was no statistically significant difference in AUC(0.966 vs 0.907,P>0.05)between RF model and LR model in the external validation set for distinguishing OP,while there was a statistically significant difference in AUC for distinguishing osteopenia(0.895 vs 0.749,P=0.009)and normal bone mass(0.975 vs 0.906,P=0.023).The RF model performance was superior to the LR model.Conclusion The radiomics model developed based on chest plain CT can be used for opportunistic OP screening with good diagnostic efficacy,and the the model based on the RF classifier outperforms the LR model.

Objective To explore the feasibility of constructing a three-classification bone status screening radiomics model on chest CT images.Methods A total of 371 patients who underwent both chest and abdominal plain CT examinations were retrospec-tively selected and randomly divided into training set(296 cases)and test set(75 cases)in a ratio of 8︰2.Additionally,110 patients were included as external validation set using the same criteria.The 120 kVp abdominal images were transmitted to a quantitative compu-ted tomography(QCT)post-processing workstation to measure the bone mineral density(BMD)of the L1-L2 vertebral bodies.Patients were classified into osteoporosis(OP)group(BMD<80 mg/cm3),osteopenia group(80 mg/cm3≤BMD≤120 mg/cm3)and normal bone mass group(BMD>120 mg/cm3)based on QCT BMD results.The automatic segmentation model was used to segment T10-T12 vertebral trabecular bone on chest CT images and the radiomics models based on random forest(RF)and logistic regres-sion(LR)was established to evaluate BMD,enabling it to simultaneously distinguish OP,osteopenia,and normal bone mass.The diag-nostic performance of the two models were evaluated using metrics such as the area under the curve(AUC),sensitivity and specificity.The DeLong test was used to compare the differences between the two models.Results In the test set,the AUC for differentiating normal bone mass were 0.948 and 0.877 for the RF and LR models,respectively;the AUC for differentiating OP were 0.942 and 0.836,respectively;and the AUC for differentiating osteopenia were 0.871 and 0.688,respectively.The performance comparison results of the models showed that there was no statistically significant difference in AUC(0.966 vs 0.907,P>0.05)between RF model and LR model in the external validation set for distinguishing OP,while there was a statistically significant difference in AUC for distinguishing osteopenia(0.895 vs 0.749,P=0.009)and normal bone mass(0.975 vs 0.906,P=0.023).The RF model performance was superior to the LR model.Conclusion The radiomics model developed based on chest plain CT can be used for opportunistic OP screening with good diagnostic efficacy,and the the model based on the RF classifier outperforms the LR model.

Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

Prostaglandin E2(PGE2)regulates a variety of cells in tumor microenvironment(TME)and plays an important role in tumor growth,metastasis and immunity.PGE2 activates different downstream signaling pathways through its key receptor prostaglandin E receptor(EP4),regulating inflammation,immune cell function and angiogenesis to promote or inhibit tumor development.EP4 shows potential application values in adjuvant chemotherapy and immunotherapy as an emerging anti-tumor target.However,future studies on the roles of EP4 in tumor microenvironment,develo-pment of safer and more effective EP4 drugs,and its application in personalized immunotherapy are needed.

Objective: This study employs metabolomics to analyze the characteristic biomarkers and metabolic pathways in the serum of pregnant women with positive thyroid peroxidase antibodies(TPOAb) during early pregnancy. The objective is to explore the relationship between thyroid dysfunction and maternal-fetal health. Methods : Early-pregnancy women undergoing antenatal check-ups for thyroid function and antibody testing at our hospital were selected. According to the TPOAb results, participants were categorized into a TPOAb-positive group and a TPOAb-negative group. The serum metabolic profiles were analyzed using liquid chromatography-tandem mass spectrometry(LC-MS/MS) technology to identify differences between the two groups. The Kyoto Encyclopedia of Genes and Genomes(KEGG) database was utilized for metabolic pathway enrichment analysis of differential metabolites. Results : A total of 79 significantly different metabolites were identified in the serum of TPOAb-positive pregnant women compared to the control group, including 20 upregulated and 59 downregulated metabolites. KEGG enrichment analysis indicated that these differential metabolites were mainly involved in 21 key metabolic pathways. Among the metabolites associated with TPOAb, 31 were identified, with 6 showing positive correlation and 25 showing negative correlation. Metabolic pathway enrichment analysis revealed that these differential metabolites were closely related to Glycerophospholipid metabolism, Valine, leucine and isoleucine biosynthesis, Glycosylphosphatidylinositol(GPI)-anchor biosynthesis, and Glycerolipid metabolism pathways. Conclusion Significant differences in metabolites and their associated metabolic pathways are identified in the serum of TPOAb-positive pregnant women during early gestation, indicating that these metabolite alterations are closely linked to thyroid dysfunction and maternal-fetal health.