Objective:To explore the molecular mechanisms by which miR-101-3p inhibits epithelial-mesenchymal transition(EMT)of gastric cancer cells and M2 polarization of macrophages.Methods:Bioinformatics software was used to analyze the expres-sion of miR-101-3p in gastric cancer and its correlation with survival.Transwell and Western blot were performed to evaluate the effect of miR-101-3p and Anxa2 on the migration,invasion and EMT of gastric cancer cells.Human monocytes(THP-1)were co-cultured with transfected gastric cancer cells.Immunofluorescence and Western blot assays were performed to assess the impact of miR-101-3p and Anxa2 on the expression of M2 macrophage markers CD206 and arginase-1(Arg-1).Immunohistochemistry and Western blot were used to analyze the expression of Anxa2 in gastric cancer tissues and cells.Bioinformatics software,dual-luciferase reporter and West-ern blot were utilized to validate the target relationship between miR-101-3p and Anxa2.Results:Compared with adjacent tissues,the level of miR-101-3p in gastric cancer tissues was significantly reduced and positively correlated with survival.Additionally,the levels of miR-101-3p in gastric cancer cells were significantly lower than those in normal gastric mucosal cells(P<0.01).Overexpression of miR-101-3p in gastric cancer cells significantly reduced their migration and invasion capabilities.This was accompanied by a marked decrease in the expression of N-cadherin and vimentin,and a significant increase in the expression of E-cadherin.In the co-cultured system,overexpression of miR-101-3p in gastric cancer cells significantly inhibited macrophage M2 polarization(P<0.01).Compared with adjacent tissues,the level of Anxa2 was significantly elevated in gastric cancer tissues.Compared with normal gastric mucosal cells,Anxa2 levels were significantly higher in gastric cancer cells(P<0.01).Anxa2 was target gene of miR-101-3p.Overexpression of Anxa2 in gastric cancer cells significantly enhanced their migration and invasion capabilities.In the co-culture system,overexpres-sion of Anxa2 in gastric cancer cells markedly promoted macrophage M2 polarization(P<0.01).Overexpression of Anxa2 could re-verse the inhibitory effects of miR-101-3p on EMT of gastric cancer cells and M2 polarization of macrophages(P<0.01).Conclusion:miR-101-3p regulates Anxa2 to inhibit EMT of gastric cancer cells and M2 polarization of macrophages,thereby suppressing the migra-tion and invasion of gastric cancer cells.

Objective:To develop and validate clinical predictive models for identifying poor short-term response to recombinant human growth hormone(rhGH) treatment in children with short stature.Methods:A retrospective analysis was conducted on 118 children diagnosed with growth hormone deficiency or idiopathic short stature who were treated at the First Affiliated Hospital of Zhengzhou University and two other hospitals between January 1, 2020, and January 1, 2024. A poor response to rhGH was defined as a height increase of less than 0.2 standard deviation score(SDS) after 6 months of rhGH treatment. LASSO regression was used to identify predictive variables from baseline and follow-up data. Two logistic regression models were conducted: Model A(incorporating baseline variables only) and model B(incorporating both baseline and follow-up variables), and nomograms were created for visualization. External data and internal resampling were used for dual validation of the models, and their performance was compared.Results:A total of 118 children with short stature were included. Six baseline predictive variables(diagnosis, initial height SDS, bone age, bone age-chronological age difference, rhGH dose, and gender) and one follow-up variable(height SDS after 3 months of rhGH treatment) were identified. Area under the curve values for Model A and Model B were 0.753(95% CI 0.696-0.811) and 0.930(95% CI 0.891-0.975), respectively. Calibration curves, decision curve analysis, and other evaluation metrics demonstrated good discrimination and clinical utility for both models. Model B, incorporating the 3-month follow-up variable, showed superior predictive performance compared to Model A. Conclusions:The clinical prediction models developed in this study(Model A and Model B) are practical and reliable tools for quantitatively, conveniently, and intuitively identifying children with short stature at risk of poor response to rhGH treatment.

Objective:To investigate the effect of PIK3CA mutations on the tumor immune microenvironment in Luminal breast cancer and evaluate the potential of Alpelisib-loaded pH-responsive polymer micelles in modulating the tumor immune microenvironment.Methods:PIK3CA mutations in breast cancer were analyzed using bioinformatics tools.A mouse xenograft model of Luminal breast cancer harboring a PIK3CA mutation was established,and alterations in the tumor immune microenvironment were examined using mass cytometry(CyTOF).During the period from August 2004 to December 2008 in Tianjin Medical University Cancer Hospital,tissue biopsies of 62 Luminal breast cancer patients in the BRCA cohort were collected Study the relationship between PIK3CA mutations and tumor immune microenvironment at the organizational level.Alpelisib-loaded polymer micelles(Alpelisib@MSPM)were synthesized,characterized,and evaluated for thera-peutic efficacy in Luminal breast cancer with PIK3CA mutations.Results:PIK3CA is one of the most frequently mutated genes in breast can-cer,with the highest prevalence in Luminal subtypes.CyTOF analysis demonstrated that PIK3CA mutations contribute to a tumor immun-osuppressive microenvironment in xenografts.Multiplex fluorescence immunohistochemistry revealed that PIK3CA-mutated tumors exhib-ited more infiltration of myeloid-derived suppressor cells(MDSCs)and less infiltration of CD8? T cells.The synthesized Alpelisib-loaded pH-re-sponsive polymer micelles had an average size of approximately 127 nm.Treatment with Alpelisib and Alpelisib@MSPM reduced tumor growth in mice with PIK3CA-mutated Luminal breast cancer.Notably,the proportion of MDSCs decreased,whereas CD8? T cell infiltration in-creased significantly,with the more pronounced effect observed in the Alpelisib@MSPM treatment group.Conclusions:PIK3CA mutations drive the formation of a tumor immunosuppressive microenvironment in Luminal breast cancer.Targeted Alpelisib delivery via pH-respons-ive polymer micelles significantly enhances therapeutic efficacy in PIK3CA-mutated breast cancer.

Objective:To investigate the effect of PIK3CA mutations on the tumor immune microenvironment in Luminal breast cancer and evaluate the potential of Alpelisib-loaded pH-responsive polymer micelles in modulating the tumor immune microenvironment.Methods:PIK3CA mutations in breast cancer were analyzed using bioinformatics tools.A mouse xenograft model of Luminal breast cancer harboring a PIK3CA mutation was established,and alterations in the tumor immune microenvironment were examined using mass cytometry(CyTOF).During the period from August 2004 to December 2008 in Tianjin Medical University Cancer Hospital,tissue biopsies of 62 Luminal breast cancer patients in the BRCA cohort were collected Study the relationship between PIK3CA mutations and tumor immune microenvironment at the organizational level.Alpelisib-loaded polymer micelles(Alpelisib@MSPM)were synthesized,characterized,and evaluated for thera-peutic efficacy in Luminal breast cancer with PIK3CA mutations.Results:PIK3CA is one of the most frequently mutated genes in breast can-cer,with the highest prevalence in Luminal subtypes.CyTOF analysis demonstrated that PIK3CA mutations contribute to a tumor immun-osuppressive microenvironment in xenografts.Multiplex fluorescence immunohistochemistry revealed that PIK3CA-mutated tumors exhib-ited more infiltration of myeloid-derived suppressor cells(MDSCs)and less infiltration of CD8? T cells.The synthesized Alpelisib-loaded pH-re-sponsive polymer micelles had an average size of approximately 127 nm.Treatment with Alpelisib and Alpelisib@MSPM reduced tumor growth in mice with PIK3CA-mutated Luminal breast cancer.Notably,the proportion of MDSCs decreased,whereas CD8? T cell infiltration in-creased significantly,with the more pronounced effect observed in the Alpelisib@MSPM treatment group.Conclusions:PIK3CA mutations drive the formation of a tumor immunosuppressive microenvironment in Luminal breast cancer.Targeted Alpelisib delivery via pH-respons-ive polymer micelles significantly enhances therapeutic efficacy in PIK3CA-mutated breast cancer.

Objective:To explore the molecular mechanisms by which miR-101-3p inhibits epithelial-mesenchymal transition(EMT)of gastric cancer cells and M2 polarization of macrophages.Methods:Bioinformatics software was used to analyze the expres-sion of miR-101-3p in gastric cancer and its correlation with survival.Transwell and Western blot were performed to evaluate the effect of miR-101-3p and Anxa2 on the migration,invasion and EMT of gastric cancer cells.Human monocytes(THP-1)were co-cultured with transfected gastric cancer cells.Immunofluorescence and Western blot assays were performed to assess the impact of miR-101-3p and Anxa2 on the expression of M2 macrophage markers CD206 and arginase-1(Arg-1).Immunohistochemistry and Western blot were used to analyze the expression of Anxa2 in gastric cancer tissues and cells.Bioinformatics software,dual-luciferase reporter and West-ern blot were utilized to validate the target relationship between miR-101-3p and Anxa2.Results:Compared with adjacent tissues,the level of miR-101-3p in gastric cancer tissues was significantly reduced and positively correlated with survival.Additionally,the levels of miR-101-3p in gastric cancer cells were significantly lower than those in normal gastric mucosal cells(P<0.01).Overexpression of miR-101-3p in gastric cancer cells significantly reduced their migration and invasion capabilities.This was accompanied by a marked decrease in the expression of N-cadherin and vimentin,and a significant increase in the expression of E-cadherin.In the co-cultured system,overexpression of miR-101-3p in gastric cancer cells significantly inhibited macrophage M2 polarization(P<0.01).Compared with adjacent tissues,the level of Anxa2 was significantly elevated in gastric cancer tissues.Compared with normal gastric mucosal cells,Anxa2 levels were significantly higher in gastric cancer cells(P<0.01).Anxa2 was target gene of miR-101-3p.Overexpression of Anxa2 in gastric cancer cells significantly enhanced their migration and invasion capabilities.In the co-culture system,overexpres-sion of Anxa2 in gastric cancer cells markedly promoted macrophage M2 polarization(P<0.01).Overexpression of Anxa2 could re-verse the inhibitory effects of miR-101-3p on EMT of gastric cancer cells and M2 polarization of macrophages(P<0.01).Conclusion:miR-101-3p regulates Anxa2 to inhibit EMT of gastric cancer cells and M2 polarization of macrophages,thereby suppressing the migra-tion and invasion of gastric cancer cells.

Objective:To develop and validate clinical predictive models for identifying poor short-term response to recombinant human growth hormone(rhGH) treatment in children with short stature.Methods:A retrospective analysis was conducted on 118 children diagnosed with growth hormone deficiency or idiopathic short stature who were treated at the First Affiliated Hospital of Zhengzhou University and two other hospitals between January 1, 2020, and January 1, 2024. A poor response to rhGH was defined as a height increase of less than 0.2 standard deviation score(SDS) after 6 months of rhGH treatment. LASSO regression was used to identify predictive variables from baseline and follow-up data. Two logistic regression models were conducted: Model A(incorporating baseline variables only) and model B(incorporating both baseline and follow-up variables), and nomograms were created for visualization. External data and internal resampling were used for dual validation of the models, and their performance was compared.Results:A total of 118 children with short stature were included. Six baseline predictive variables(diagnosis, initial height SDS, bone age, bone age-chronological age difference, rhGH dose, and gender) and one follow-up variable(height SDS after 3 months of rhGH treatment) were identified. Area under the curve values for Model A and Model B were 0.753(95% CI 0.696-0.811) and 0.930(95% CI 0.891-0.975), respectively. Calibration curves, decision curve analysis, and other evaluation metrics demonstrated good discrimination and clinical utility for both models. Model B, incorporating the 3-month follow-up variable, showed superior predictive performance compared to Model A. Conclusions:The clinical prediction models developed in this study(Model A and Model B) are practical and reliable tools for quantitatively, conveniently, and intuitively identifying children with short stature at risk of poor response to rhGH treatment.

Scientific and rigorous selection of theories,models or frameworks is the premise of high-quality nursing research.This work introduces the development process,basic information,application in nursing of T-CaST(Theory Comparison and Selection Tool,T-CaST),and shows the specific application process of this tool through examples,to provide evaluation methods for nursing scholars to choose appropriate guiding theories in the research process,and has guiding significance for developing high-quality nursing research under the guidance of theories,models or frameworks.

BACKGROUND:Autophagy and ferroptosis play important roles in the development of chronic kidney disease,but the molecular mechanisms and gene targets related to autophagy and ferroptosis in renal tissue of chronic kidney disease are still unclear. OBJECTIVE:To screen differentially expressed genes in chronic kidney disease-related datasets based on bioinformatics,and to explore potential key biomarkers suitable for screening renal function progression in patients with chronic kidney disease. METHODS:(1)The GSE137570 dataset was obtained from GEO database to screen the differentially expressed genes by Networkanalyst database analysis.Ferroptosis and autophagy related targets were obtained by OMIM,GENECARD,FerrDb and HAMdb databases.The respective data were intersected to obtain autophagy-ferroptosis related differentially expressed genes in chronic kidney disease for parallel enrichment analysis.The STRING website was used to construct the protein-protein interaction network of differentially expressed genes,which was imported into Cytoscape software and analyzed by MCODE and Cytohubba plug-in to screen potential core targets.Enrichment analysis was performed to obtain the functions of these potential core targets.(2)In the in vitro experiment,mouse renal tubular epithelial cells were divided into two groups:the control group received no intervention,while the model group was stimulated with 5 ng/mL transforming growth factor β1 for 24 hours to induce mesenchymal transformation of renal tubular epithelial cells.Flow cytometry was used to measure the levels of reactive oxygen species and changes in mitochondrial membrane potential in the cells.RT-PCR was employed to assess ferroptosis,autophagy-related markers,and the mRNA expression of potential core targets in the cells. RESULTS AND CONCLUSION:After screening the GSE137570 dataset,a total of 480 differentially expressed genes were obtained,including 104 upregulated genes and 376 downregulated genes(log2|(FC)|>1,P<0.05).There were 562 ferroptosis-related targets and 1 266 autophagy-related targets obtained from the OMIM,GENECARD,FerrDb,and HAMdb databases.Intersection of differentially expressed genes with ferroptosis-and autophagy-related targets yielded 15 ferroptosis-related targets and 18 autophagy-related targets,respectively.The enrichment analysis results indicate that ferroptosis-related differentially expressed genes are primarily involved in biological processes such as sulfur amino acid metabolism,neutrophil degranulation,and ferroptosis signaling pathways.Autophagy-related differentially expressed genes are mainly enriched in biological processes such as platelet degranulation,extracellular matrix degradation,and receptor tyrosine kinase signaling.After screened by MCODE and CytoHubba,key genes were identified in the protein-protein interaction network,including CD44,ALB,TIMP1,PLG,CCL2,and DPP4.Immune infiltration analysis results indicate that immune cells such as B cells,CD4+ T cells,NK cells,and monocytes show significant differential expression in renal tissue after chronic kidney disease,and the core targets are also significantly correlated with these immune cells(P<0.05).The results of receiver operator characteristic curve analysis further demonstrate that the pathological progression of chronic kidney disease can be effectively diagnosed by CD44,ALB,TIMP1,PLG,CCL2,and DPP4.Single-cell sequencing results show that,except for PLG,the expression of target genes in the renal tissue of mice in each model group is generally consistent with the results of this experiment.RT-PCR results demonstrate that,for the validation of autophagy and ferroptosis phenotypes,compared with the control group,the model group shows a significant decrease in mRNA expression of LC3B,Nrf2,and SLC7A11(P<0.05),and a significant increase in P62 mRNA expression(P<0.05).Regarding the validation of potential core targets,compared with the control group,the model group exhibits a significant decrease in mRNA expression of ALB and PLG(P<0.05),and a significant increase in TIMP1 and CCL2 mRNA expression(P<0.05).Overall,these findings indicate that,through bioinformatics analysis and experimental validation,CD44,ALB,TIMP1,PLG,and CCL2 are abnormally expressed in the renal tissue of patients with chronic kidney disease,closely correlated with estimated glomerular filtration rate and tubulointerstitial fibrosis,and maybe play a predictive role in the progression of chronic kidney disease.

Type 1 diabetes mellitus (T1DM) is the main type of diabetes in children, which seriously endangers children′s health.With the development of technology, the emergence of artificial pancreas has brought new progress for the treatment of T1DM.Artificial pancreas can imitate the insulin physiological secretion of pancreas β cells to control glucose, and achieve close-loop management by accurately regulating insulin infusion through continuous glucose monitoring, insulin pump and control algorithms.Here the current clinical studies on the safety, effectiveness and limitations of artificial pancreas in the treatment of T1DM were reviewed.It is expected to provide another choice for children with T1DM.

Objective:To analyze the application effect of the information platform based on the Internet of Things (IoT) in the screening and management of patients with chronic obstructive pulmonary disease (COPD).Methods:In this cross-sectional study, 151 062 residents who participated in the screening in the districts covered by 33 general hospitals and 289 primary medical institutions within the framework of Henan Provincial Center for COPD Prevention and Treatment from November 2021 to October 2022 were included as the subjects. Spirometer based on the IoT was used to conduct pulmonary function tests for subjects who scored 16 points or more with COPD Screening Questionnaire (COPD-SQ), and the subjects were evaluated and managed through the structured electronic data in the information platform. The distribution characteristics and follow-up of the subjects and COPD patients were described and the application effect of this strategy in patients screening and management was analyzed.Results:A total of 151 062 residents with complete basic information in the information platform completed the questionnaire. High-risk population of COPD accounted for 26.5% (40 042/151 062) of the population who received the questionnaire screening, and more than 50% had respiratory symptoms, such as chronic cough (59.4%), or shortness of breath (77.6%). The proportion of high-risk population increased with age, especially after 50 years old. Compared with non-smokers, the proportion of high-risk group was significantly higher (77.1% vs 16.4%) in the group with smoking index over 600. Biofuel exposure (61.3% vs 22.1%) and family history of respiratory diseases (64.2% vs 22.6%) were associated with an increased proportion of high-risk groups, with statistically significant differences ( P<0.001). 5 268 patients were diagnosed with COPD by pulmonary function tests, and the prevalence of COPD in high-risk groups was 27.8% (5 268/18 965), the prevalence rate of male was 34.0% (3 942/11 588), which was higher than that of female 18.0% (1 326/7 377). 2 950 patients (56.0%) completed at least one follow-up of symptom questionnaire and 510 patients (9.7%) completed more than one follow-up of pulmonary function test. Conclusion:The screening and management strategy of COPD based on the IoT and information technology can improve the efficiency of COPD screening, and improve the status quo of under-diagnosis and discontinuous follow-up of COPD.