BACKGROUND:Titanium surface micro-nano structure modification is a hot research field in titanium implant surface treatment.The diabetic hyperglycemia environment will affect the stable bonding between titanium implant and bone tissue,so it is necessary to explore the surface micro-nano structure modification to improve the osteogenic activity of titanium implant in high glucose environment.OBJECTIVE:To investigate the effect of gold nanoparticle@mesoporous silica nanoparticles(AuNPs@MSNs)coating on osteogenic activity of osteoblasts under high glucose in vitro.METHODS:Gold nanoparticle suspension and mesoporous silica were prepared respectively,and the two were mixed in deionized water in a certain proportion to prepare gold nanoparticle@mesoporous silica suspension.Titanium sheets were taken and divided into three groups for treatment:the smooth group was treated with water sandpaper;the nanotube group was treated with water sandpaper and then anodized to prepare titanium dioxide nanotube coating,and the experimental group prepared titanium dioxide nanotube coating and then immersed in gold nanoparticle@mesoporous silica suspension to prepare gold nanoparticle@mesoporous silica nanoparticles coating.The microscopic morphology and hydrophilicity of the surface of the three groups of titanium sheets were characterized.Rat bone marrow mesenchymal stem cells were inoculated on the surface of the three groups of titanium sheets.Cell proliferation was detected by cell live/dead fluorescence staining and CCK-8 assay.Cell adhesion was detected by DAPI/phalloidin staining.Rat bone marrow mesenchymal stem cells were inoculated on the surface of the three groups of titanium sheets,and high-glucose osteogenic induction medium was added for culture.Osteogenic differentiation was detected by alkaline phosphatase and Alizarin Red S staining.RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of the titanium sheet in the smooth group was uniform and flat.The titanium dioxide nanotube arrays in the nanotube group were closely arranged on the surface,and the titanium sheet in the experimental group was loaded with gold nanoparticle@mesoporous silica on the surface and inside of the titanium dioxide nanotubes.The hydrophilicity of the titanium sheets in the nanotube group and the experimental group was better than that in the smooth group.(2)The results of cell live/dead fluorescence staining exhibited that the cell viability on the surface of the three groups of titanium sheets was higher than 90%.The results of CCK-8 assay show that the cell proliferation rate in the experimental group was higher than that in the smooth group and the nanotube group.The results of DAPI/phalloidin staining showed that the titanium dioxide nanotube coating and the gold nanoparticle@mesoporous silica nanoparticles coating were more conducive to cell adhesion.(3)The results of alkaline phosphatase and Alizarin Red S staining showed that the alkaline phosphatase activity and extracellular matrix mineralization of the cells on the titanium sheet surface in the experimental group were higher than those in the smooth group and the nanotube group.(4)The results show that the gold nanoparticle@mesoporous silica nanoparticles coating can enhance the biological activity of the titanium surface and promote osteogenic differentiation in a high glucose environment.

Objective To investigate the effect of resveratrol on the proliferation,apoptosis,and migration of breast cancer cells and its mechanism and correlation with immune cell infiltration.Methods The network pharmacology and bioinformatics(GEPIA and KM-PLOT databases)were used to predict the target genes of breast cancer regulated by resveratrol,and their expression levels in breast cancer and correlations with immune cell infiltration were verified.The effects of resveratrol on the proliferation,cell cycle and apopto-sis,and migration of breast cancer cells were determined by the CCK-8 assay,flow cytometry,and cell scratch test,respectively.The mRNA expression levels of related target genes were detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Pearson correlation analysis was used to analyze the correlations of the expression levels of related genes with immune cell infiltration.Results The expression levels of TP53 and VEGFA genes in breast cancer tissues were significantly higher than those in normal tissues(Z=-4.181 and-8.763,P＜0.05).In the GEPIA database,the expression level of CDKN1A gene in breast cancer tis-sues was significantly higher than that in normal tissues(Z=-2.135,P＜0.05).In the KMPLOT database,the expression level of HIF1α gene in breast cancer tissues was significantly higher than that in normal tissues(Z=-2.269,P＜0.05).Pearson correlation a-nalysis showed that the expression level of TP53 gene was positively correlated with B cell infiltration(partial.cor=0.102,P＜0.01).The expression level of HIF-1α was positively correlated with the infiltration of CD8+T cells,CD4+T cells,monocytes,neutrophils,and dendritic cells(partial.cor=0.39,0.159,0.284,0.325,and 0.294,P＜0.01).The expression level of VEGFA gene was positive-ly correlated with neutrophil infiltration(partial.cor=0.141,P＜0.01).The expression level of CDKN1A gene was positively correlated with the infiltration of CD8+T cells,monocytes,neutrophils,and dendritic cells(partial.cor=0.081,0.209,0.11,and 0.09,P＜0.01).Resveratrol could inhibit the proliferation of breast cancer cells,and the IC50 and IC25 values of breast cancer cells were 150 μmol/L and 50 μmol/L,respectively,after 48 hours of treatment with resveratrol.In addition,resveratrol could also arrest breast cancer cells in G1 phase,induce their apoptosis,and inhibit their migration.After treating breast cancer cells with resveratrol for 24 hours,with the increase of resveratrol concentration from 50 μmol/L to 150 μmol/L,the mRNA expression levels of TP53 and HIF1α genes increased gradually,with a significant difference between the two groups(P＜0.05).After treating breast cancer cells with res-veratrol for 48 hours,the expression level of VEGFA mRNA was significantly decreased,and there was a significant difference between the two groups(P＜0.05).Conclusion TP53,HIF-1α,VEGFA,and CDKN1A genes are the action targets of resveratrol in breast cancer,which are mainly involved in the regulation of immune cell infiltration in breast cancer.Resveratrol inhibits the proliferation of breast cancer cells,induces cell cycle arrest and apoptosis,and inhibits cell migration by regulating the P53-HIF1α/CDKN1A-VEGFA signaling pathway.

Objective To investigate the effect of resveratrol on the proliferation,apoptosis,and migration of breast cancer cells and its mechanism and correlation with immune cell infiltration.Methods The network pharmacology and bioinformatics(GEPIA and KM-PLOT databases)were used to predict the target genes of breast cancer regulated by resveratrol,and their expression levels in breast cancer and correlations with immune cell infiltration were verified.The effects of resveratrol on the proliferation,cell cycle and apopto-sis,and migration of breast cancer cells were determined by the CCK-8 assay,flow cytometry,and cell scratch test,respectively.The mRNA expression levels of related target genes were detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Pearson correlation analysis was used to analyze the correlations of the expression levels of related genes with immune cell infiltration.Results The expression levels of TP53 and VEGFA genes in breast cancer tissues were significantly higher than those in normal tissues(Z=-4.181 and-8.763,P＜0.05).In the GEPIA database,the expression level of CDKN1A gene in breast cancer tis-sues was significantly higher than that in normal tissues(Z=-2.135,P＜0.05).In the KMPLOT database,the expression level of HIF1α gene in breast cancer tissues was significantly higher than that in normal tissues(Z=-2.269,P＜0.05).Pearson correlation a-nalysis showed that the expression level of TP53 gene was positively correlated with B cell infiltration(partial.cor=0.102,P＜0.01).The expression level of HIF-1α was positively correlated with the infiltration of CD8+T cells,CD4+T cells,monocytes,neutrophils,and dendritic cells(partial.cor=0.39,0.159,0.284,0.325,and 0.294,P＜0.01).The expression level of VEGFA gene was positive-ly correlated with neutrophil infiltration(partial.cor=0.141,P＜0.01).The expression level of CDKN1A gene was positively correlated with the infiltration of CD8+T cells,monocytes,neutrophils,and dendritic cells(partial.cor=0.081,0.209,0.11,and 0.09,P＜0.01).Resveratrol could inhibit the proliferation of breast cancer cells,and the IC50 and IC25 values of breast cancer cells were 150 μmol/L and 50 μmol/L,respectively,after 48 hours of treatment with resveratrol.In addition,resveratrol could also arrest breast cancer cells in G1 phase,induce their apoptosis,and inhibit their migration.After treating breast cancer cells with resveratrol for 24 hours,with the increase of resveratrol concentration from 50 μmol/L to 150 μmol/L,the mRNA expression levels of TP53 and HIF1α genes increased gradually,with a significant difference between the two groups(P＜0.05).After treating breast cancer cells with res-veratrol for 48 hours,the expression level of VEGFA mRNA was significantly decreased,and there was a significant difference between the two groups(P＜0.05).Conclusion TP53,HIF-1α,VEGFA,and CDKN1A genes are the action targets of resveratrol in breast cancer,which are mainly involved in the regulation of immune cell infiltration in breast cancer.Resveratrol inhibits the proliferation of breast cancer cells,induces cell cycle arrest and apoptosis,and inhibits cell migration by regulating the P53-HIF1α/CDKN1A-VEGFA signaling pathway.

BACKGROUND:Titanium surface micro-nano structure modification is a hot research field in titanium implant surface treatment.The diabetic hyperglycemia environment will affect the stable bonding between titanium implant and bone tissue,so it is necessary to explore the surface micro-nano structure modification to improve the osteogenic activity of titanium implant in high glucose environment.OBJECTIVE:To investigate the effect of gold nanoparticle@mesoporous silica nanoparticles(AuNPs@MSNs)coating on osteogenic activity of osteoblasts under high glucose in vitro.METHODS:Gold nanoparticle suspension and mesoporous silica were prepared respectively,and the two were mixed in deionized water in a certain proportion to prepare gold nanoparticle@mesoporous silica suspension.Titanium sheets were taken and divided into three groups for treatment:the smooth group was treated with water sandpaper;the nanotube group was treated with water sandpaper and then anodized to prepare titanium dioxide nanotube coating,and the experimental group prepared titanium dioxide nanotube coating and then immersed in gold nanoparticle@mesoporous silica suspension to prepare gold nanoparticle@mesoporous silica nanoparticles coating.The microscopic morphology and hydrophilicity of the surface of the three groups of titanium sheets were characterized.Rat bone marrow mesenchymal stem cells were inoculated on the surface of the three groups of titanium sheets.Cell proliferation was detected by cell live/dead fluorescence staining and CCK-8 assay.Cell adhesion was detected by DAPI/phalloidin staining.Rat bone marrow mesenchymal stem cells were inoculated on the surface of the three groups of titanium sheets,and high-glucose osteogenic induction medium was added for culture.Osteogenic differentiation was detected by alkaline phosphatase and Alizarin Red S staining.RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of the titanium sheet in the smooth group was uniform and flat.The titanium dioxide nanotube arrays in the nanotube group were closely arranged on the surface,and the titanium sheet in the experimental group was loaded with gold nanoparticle@mesoporous silica on the surface and inside of the titanium dioxide nanotubes.The hydrophilicity of the titanium sheets in the nanotube group and the experimental group was better than that in the smooth group.(2)The results of cell live/dead fluorescence staining exhibited that the cell viability on the surface of the three groups of titanium sheets was higher than 90%.The results of CCK-8 assay show that the cell proliferation rate in the experimental group was higher than that in the smooth group and the nanotube group.The results of DAPI/phalloidin staining showed that the titanium dioxide nanotube coating and the gold nanoparticle@mesoporous silica nanoparticles coating were more conducive to cell adhesion.(3)The results of alkaline phosphatase and Alizarin Red S staining showed that the alkaline phosphatase activity and extracellular matrix mineralization of the cells on the titanium sheet surface in the experimental group were higher than those in the smooth group and the nanotube group.(4)The results show that the gold nanoparticle@mesoporous silica nanoparticles coating can enhance the biological activity of the titanium surface and promote osteogenic differentiation in a high glucose environment.

Objective:To define the concept of proactive health behavior.Methods:Literature related to proactive health behavior was retrieved from China National Knowledge Infrastructure, Wanfang Data, VIP, SinoMed, PubMed, Web of Science, Embase, and Ovid databases, with a retrieval time frame from database inception to March 1, 2025. Walker and Avant's concept analysis method was used to analyze the concept of proactive health behavior.Results:A total of 46 articles related to proactive health behavior were included. Proactive health behavior encompasses five key attributes: self-initiation, long-term persistence, multidimensional integration, future orientation, and overcoming barriers. Antecedents include individual factors, supportive factors, and environmental factors. Outcomes include promoting individual health and improving quality of life, enhancing personal health literacy, reducing disease burden, and fostering a proactive health atmosphere.Conclusions:The concept attributes of proactive health behavior were clarified through concept analysis. Future researchers may develop proactive health behavior assessment tools and construct intervention strategies based on their connotation.

Objective To analyze the influencing factors of health behaviors in stroke patients,and explore the chain mediating effects of self-efficacy and e-health literacy between the perception of stroke recurrence risk and health behaviors in stroke patients,providing a reference for strengthening the health behavior and reducing recurrence risk in stroke patients.Methods 249 stroke patients were selected as the research objects from March to September 2024 in a tertiary hospital in Shanghai,China.Patients were surveyed using General Information Questionnaire,Stroke Recurrence Risk Perception Scale,Stroke Health Behavior Scale(HBS-SP),Chronic Disease Self-Efficacy Scale(CDSES),and the e-health Literacy Scale(e-HEALS).Pearson correlation analysis was used to explore the correlations among various variables,and SPSS 26.0 software macro program Process Model 6 was used to conduct chain mediation model test.Results The scores of Recurrence Risk Perception,HBS-SP,CDSES and e-HEALS of stroke patients were(42.88±6.48)scores,(68.32±14.13)scores,(6.87±1.55)scores and(27.76±6.06)scores,and all the variables were positively correlated(P<0.01).The mediating effect model showed that self-efficacy and e-health literacy played a chain mediating role in the recurrence risk perception and health behavior in stroke patients,with an effect size of 0.488,accounting for 37.22%of the total effect.Conclusions The recurrence risk perception and health behavior of stroke patients are both at a moderate level.In the future,we can establish a mobile management platform to provide comprehensive health management for stroke patients.Further exploration of strategies to enhance stroke patients'self-efficacy and channels for online health education could be pursued to improve their health behaviors.

Programmed cell death is an important defense mechanism of the body, which monitors internal lesions and defends external infections to maintain the stability of the body.In the past, there were two main types of cell death: apoptosis and necrosis.With the development of scientific research, new cell death modes, such as pyroptosis and ferroptosis, have attracted much attention and are involved in the occurrence and development of diabetic retinopathy (DR).Many pathogenic factors, such as oxidative stress, hyperglycemia and inflammation, lead to the death of retinal cells in different ways, such as apoptosis, pyroptosis and ferroptosis.Apoptosis is the earliest pathological response of DR, which occurs at the initial stage of oxidative stress, and the integrity of cell membranes is maintained at the early stage of apoptosis.Apoptotic cells are cleared by phagocytes in the tissue before dissolution, which avoids unnecessary inflammation.Pyroptosis is activated by Caspase-1, then cleaves GSDMD, which can lead to pore formation and osmotic cell lysis, resulting in inflammation and immune response.Ferroptosis involves lipid peroxidation and abnormal iron homeostasis.Lipid peroxidation and glutathione depletion are the main markers of ferroptosis.The three cell death modes are independent and interrelated, and play a role in the occurrence and development of diseases together with other cell death modes.This article reviews the current status of cell apoptosis, pyroptosis and ferroptosis in DR.

Objective:To define the concept of proactive health behavior.Methods:Literature related to proactive health behavior was retrieved from China National Knowledge Infrastructure, Wanfang Data, VIP, SinoMed, PubMed, Web of Science, Embase, and Ovid databases, with a retrieval time frame from database inception to March 1, 2025. Walker and Avant's concept analysis method was used to analyze the concept of proactive health behavior.Results:A total of 46 articles related to proactive health behavior were included. Proactive health behavior encompasses five key attributes: self-initiation, long-term persistence, multidimensional integration, future orientation, and overcoming barriers. Antecedents include individual factors, supportive factors, and environmental factors. Outcomes include promoting individual health and improving quality of life, enhancing personal health literacy, reducing disease burden, and fostering a proactive health atmosphere.Conclusions:The concept attributes of proactive health behavior were clarified through concept analysis. Future researchers may develop proactive health behavior assessment tools and construct intervention strategies based on their connotation.

Programmed cell death is an important defense mechanism of the body, which monitors internal lesions and defends external infections to maintain the stability of the body.In the past, there were two main types of cell death: apoptosis and necrosis.With the development of scientific research, new cell death modes, such as pyroptosis and ferroptosis, have attracted much attention and are involved in the occurrence and development of diabetic retinopathy (DR).Many pathogenic factors, such as oxidative stress, hyperglycemia and inflammation, lead to the death of retinal cells in different ways, such as apoptosis, pyroptosis and ferroptosis.Apoptosis is the earliest pathological response of DR, which occurs at the initial stage of oxidative stress, and the integrity of cell membranes is maintained at the early stage of apoptosis.Apoptotic cells are cleared by phagocytes in the tissue before dissolution, which avoids unnecessary inflammation.Pyroptosis is activated by Caspase-1, then cleaves GSDMD, which can lead to pore formation and osmotic cell lysis, resulting in inflammation and immune response.Ferroptosis involves lipid peroxidation and abnormal iron homeostasis.Lipid peroxidation and glutathione depletion are the main markers of ferroptosis.The three cell death modes are independent and interrelated, and play a role in the occurrence and development of diseases together with other cell death modes.This article reviews the current status of cell apoptosis, pyroptosis and ferroptosis in DR.

Objective:To summarize and analyze the clinical and genetic characteristics of children with nephronophthisis (NPHP) so as to improve clinicians′ understanding of this disease and provide reference for its early diagnosis.Methods:Retrospective case series study.The clinical and genetic data of 15 children with NPHP diagnosed by gene detection in the Department of Nephrology, Beijing Children′s Hospital, Capital Medical University from January 2016 to June 2024 were retrospectively analyzed.Non-normal distribution measurement data were expressed as median (range) and analyzed by rank sum test.Results:There were 10 boys and 5 girls in the 15 patients included, with a median age of onset of 6.85 years (1.16-14.00 years).The initial clinical manifestations were lack of specificity, and most patients presented non-specific symptoms such as fatigue, growth retardation, polydipsia and polyuria initially.At the first visit, 14 children had renal function damage, and 5 of them had end-stage renal disease (ESRD).Another 4 children progressed to ESRD during the follow-up, and 2 children died during the follow-up.The median age of ESRD or death was 12.25 years (1.87-15.00 years).Renal ultrasound changes were observed in all 15 children, including parenchymal echo enhancement in 14 cases, unclear medullary boundary in 10 cases, renal cysts in 7 cases, and renal volume reduction in 2 cases.Renal histopathological examination was performed in 2 cases, and their results were consistent with the pathological manifestations of early and late NPHP, respectively.NPHP can be complicated with renal, intracranial, cardiac and other extrarenal manifestations. NPHP1, NPHP4, NPHP2, NPHP3, NPHP11, NPHP13 and NPHP18 mutations were detected in 5, 4, 2, 1, 1, 1, and 1 patient, respectively.Previously unreported mutation sites were revealed, including c. 594-3C>G, c.1415T>C, c.37553769delTTCGGGGGACACAGA, c.4067A>C, c.1196A>G, c.4140+ 3G>C, c.1196A>G, c.2101-20A>C, c.643C>T and c. 2087T>C. Conclusions:The onset of NPHP is insidious and it often presents with non-specific manifestations.Laboratory and imaging examinations lack specificity.Generally, renal insufficiency is an early symptom of NPHP, and it progresses rapidly, resulting in poor prognosis.Most patients lose the opportunity for kidney biopsy.NPHP should be considered in children with early onset and unexplained renal insufficiency, and genetic testing is helpful for early diagnosis.