ObjectiveTo investigate the protective effect of genistein （Gen） on etoposide-induced chondrocyte senescence and its underlying mechanism. MethodsThe C28/I2 cell line was treated with different concentrations of Gen and etoposide， and the cell viability was detected by the CCK-8 assay. The senescence model of C28/I2 chondrocytes was induced by etoposide， with Gen intervention. Senescence-associated β-galactosidase （SA-β-gal） staining was performed to detect the senescence-positive rate and staining characteristics of chondrocytes. The expressions of peroxiredoxin 6 （Prdx6）， cyclin-dependent kinaseto clarify the functional necessity of Prdx6. ResultsCompared with the etoposide group， the C28/I2 chondrocyte viability significantly increased （P<0.01）， the expression ofsenescence-associated proteins p21 and p16 decreased （P<0.01， P<0.05）， the expression of senescence-associated genes p21 and p16 reduced （both P<0.01）， the fluorescence intensity of senescence-associated proteins p21 and p16 was diminished （P<0.05， P<0.01）， and the proportion of SA-β-gal-positive cells decreased （P<0.01） in the Gen+etoposide group. Compared with the Control group， the expression of Prdx6 was downregulated in the etoposide group （P<0.05）. Compared with the etoposide group， the expression of Prdx6 was upregulated in the Gen+etoposide group （P<0.01）. Compared with the Control group， the GPx activity significantly decreased in the si-Prdx6 group （P<0.01）. Furthermore， compared with the si-Prdx6 group， the GPx activity increased in the si-Prdx6+Gen group （P<0.05）. Molecular docking results revealed that Gen formed hydrogen bond interactions with the active site of Prdx6. After Prdx6 knockdown， the expression of senescence-associated genes p21 and p16 and the fluorescence intensity of senescence-associated proteins p21 and p16 both increased in the Gen+etoposide+si-Prdx6 group （both P<0.01）. ConclusionGen can inhibit etoposide-induced senescence of C28/I2 chondrocytes by upregulating the expression of Prdx6. This study provides potential drug targets and experimental basis for the prevention and treatment of chondrocyte senescence-related diseases.

ObjectiveTo investigate the effects and mechanisms of pulchinenoside A （PSA） on tumor necrosis factor-α （TNF-α） -induced abnormal proliferation， migration， and invasion of synovial fibroblasts. MethodsA synovitis model was established by stimulating SW982 synovial cells with TNF-α. The low-density lipoprotein receptor-related protein 1 （LRP1） was knocked down using LRP1-specific siRNA or inhibited by the receptor-associated protein （RAP）. Cells were treated with various concentrations of PSA， and cell viability was assessed by CCK-8 assay. Protein levels of LRP1， matrix metalloproteinase-3 （MMP3）， and N-cadherin were measured by Western blotting. Proliferation was evaluated using an EdU incorporation assay. Migration and invasion capacities were examined by Transwell and wound-healing assays. mRNA expression of LRP1， MMP3， N-cadherin， IL-1β， IL-6， and TNF-α was detected by reverse transcription quantitative real-time PCR （RT-qPCR）. Immunofluorescence staining was used to visualize the expression of MMP3 and N-cadherin. The involvement of LRP1 was further verified with the inhibitor RAP. ResultsCompared with the TNF-α-treated model group， PSA treatment significantly reduced SW982 cell viability （P<0.05）， downregulated MMP3 and N-cadherin expression （both P<0.01）， and decreased the proportion of EdU-positive cells （P<0.05）. Moreover， TNF-α stimulation upregulated LRP1 expression compared with normal controls （P<0.01）， whereas PSA treatment reversed this increase （P<0.05）. LRP1 knockdown or inhibition markedly decreased MMP3 and N-cadherin levels compared with the model group （both P<0.01）. Similarly， the combination of PSA and RAP led to significant reductions in MMP3 and N-cadherin expression compared with the model group （both P<0.01）. ConclusionPSA inhibits TNF-α-induced abnormal proliferation， migration， and invasion of synovial， at least in part， by downregulating LRP1 expression.

Objective : To explore the effects and mechanisms of Kobophenol A ( KPA) on lipopolysaccharide ( LPS) -induced M1 macrophage polarization，and to provide a theoretical basis for the treatment of inflammatory immune diseases and the development of new drugs． Methods: The M1 macrophage polarization model of RAW264. 7 was established by LPS induction，and the peroxiredoxin 6 ( Prdx6) knockdown model was constructed using the Prdx6 inhibitor MJ33 and Prdx6-siRNA．RAW264. 7 cells，a mouse macrophage cell line，were treated with various concentrations of KPA． Cell viability was assessed using the CCK-8 assay．The expression levels of Prdx6 and M1 macrophage polarization-related proteins，including inducible nitric oxide synthase ( iNOS) and cyclooxygenase-2 ( COX-2) ，were detected by Western blot and immunofluorescence staining．The expression levels of Prdx6 and M1 macrophage polarization-related genes iNOS，interleukin-6 ( IL-6) ，and tumor necrosis factor α ( TNF-α) ，were measured by RT-qPCR. Flow cytometry was employed to detect the expression of cluster of differentiation 86 ( CD86) ，a marker of M1 macrophages． Results: Compared with the LPS-induced M1 macrophage polarization model ， KPA significantly reversed the morphological changes of M1 macrophage polarization in RAW264. 7 macrophages and decreased the expression of M1 macrophage polarization-related proteins iNOS，COX- 2，CD86 and related genes iNOS，IL-6，TNF-α ( all P＜0. 05) ．In addition，LPS significantly downregulated the expression of Prdx6 in RAW264. 7 macrophages，while KPA upregulated the expression of Prdx6．Moreover，treatment with the Prdx6 inhibitor MJ33 significantly upregulated the expression of iNOS，a marker of M1 macrophage polarization，in RAW264. 7 macrophages，whereas treatment with KPA significantly downregulated the expression of iNOS ( all P＜0. 05) ． Conclusion KPA inhibits LPS-induced M1 polarization of RAW264. 7 macrophages by upregulating the expression of Prdx6．

Objective : To identify autophagy-related genes involved in pulmonary infection caused by the highly drug-resistant and virulent methicillin-resistant Staphylococcus aureus strain USA300 ( USA300) ，and to explore the underlying molecular mechanisms ， thereby providing potential targets for immunotherapy． Methods: The GSE220943 dataset of a USA300-induced pulmonary infection mouse model was obtained from the GEO database． Differentially expressed genes ( DEGs ) were identified using the DESeq2 package． Autophagy-related genes ( ARGs) were retrieved from the MSigDB and Autophagy databases．Weighted gene co-expression network analysis ( WGCNA) was performed to construct gene co-expression modules．Genes overlapping among DEGs，ARGs，and WGCNA modules were identified as autophagy-related DEGs．Gene Ontology ( GO) enrichment analysis was con- ducted using the clusterProfiler R package，while Kyoto Encyclopedia of Genes and Genomes ( KEGG) pathway en- richment analysis was performed via the Metascape platform．Immune cell infiltration was analyzed using the Immu- CellAI-mouse website．A protein - protein interaction ( PPI) network was constructed using the STRING database， and hub genes were identified through topological analysis in Cytoscape． Receiver operating characteristic curve ( ROC) curves were plotted via the website https: / /www．bioinformatics．com．cn． Finally，key gene expression was validated in mouse lung tissues by real-time quantitative reverse transcription PCR ( RT-qPCR) ． Results: A total of 6 135，4 075，3 680，and 2 342 differentially expressed genes ( DEGs) were identified at 12，24，48，and 96 hours post-infection，respectively．By integrating DEGs，autophagy-related genes ( ARGs) ，and WGCNA mod- ules，19 autophagy-related DEGs were identified． GO and KEGG enrichment analyses indicated that these genes were mainly involved in CD4 + T cell activation and regulation，innate immune responses，and autophagosome mem- brane formation．Immune infiltration analysis revealed that innate immune cells such as neutrophils and dendritic cells predominated during the early phase of infection，while γδ T cells and M2 macrophages became more promi- nent in the later stages．PPI network analysis identified 12 hub autophagy-related genes，among which three upreg- ulated key genes ( Eif2ak2，Ikbke，and Nfkbiz) were further confirmed．The area under the ROC curve for all three genes was 1. 000．RT-qPCR validation demonstrated significantly elevated expression of these three genes in lung tissues at 24 hours post-infection ( all P＜0. 05) ． Conclusion Eif2ak2，Ikbke，and Nfkbiz may be involved in the pulmonary infection caused by USA300 by promoting autophagy and hold promise as potential targets for immuno- therapy．

Objective::To examine the impact of hypertensive disorders of pregnancy (HDP) on offspring metabolomics.Methods::We searched five databases: PubMed, Ovid Embase, MEDLINE, Web of Science, and China National Knowledge Infrastructure, and included studies that reported metabolomics among human offspring born to HDP-complicated pregnancies.Results::Database search yielded 4054 articles, and after full-text screening, ten observational studies met inclusion criteria. Half of the studies had a sample size of less than 100 and were all observational studies in preeclampsia (PE) and gestational hypertension.Neonates were the most focused group in all included studies. Offspring born to HDP-complicated pregnancies exhibited statistically significant variations in blood metabolomics compared to their counterparts, characterized by amino acids, lipids, carnitine, and others (e.g., 1α,25-(OH) 2-D). Most studies reported a significant increase in differential metabolites of offspring born to HDP-complicated pregnancies. Four studies ( n = 1109) measured lipids-related metabolites, and all consistently showed that offspring born to PE-complicated pregnancies had significantly higher concentrations than non-PE exposed offspring. Conclusion::The existing evidence suggests an intergenerational effect of HDP on offspring metabolomics. Long-term follow-up studies are needed to advance the health effects of related adverse health outcomes and inform the prevention of offspring’s health.

Objective::To examine the impact of hypertensive disorders of pregnancy (HDP) on offspring metabolomics.Methods::We searched five databases: PubMed, Ovid Embase, MEDLINE, Web of Science, and China National Knowledge Infrastructure, and included studies that reported metabolomics among human offspring born to HDP-complicated pregnancies.Results::Database search yielded 4054 articles, and after full-text screening, ten observational studies met inclusion criteria. Half of the studies had a sample size of less than 100 and were all observational studies in preeclampsia (PE) and gestational hypertension.Neonates were the most focused group in all included studies. Offspring born to HDP-complicated pregnancies exhibited statistically significant variations in blood metabolomics compared to their counterparts, characterized by amino acids, lipids, carnitine, and others (e.g., 1α,25-(OH) 2-D). Most studies reported a significant increase in differential metabolites of offspring born to HDP-complicated pregnancies. Four studies ( n = 1109) measured lipids-related metabolites, and all consistently showed that offspring born to PE-complicated pregnancies had significantly higher concentrations than non-PE exposed offspring. Conclusion::The existing evidence suggests an intergenerational effect of HDP on offspring metabolomics. Long-term follow-up studies are needed to advance the health effects of related adverse health outcomes and inform the prevention of offspring’s health.

Objective·To explore the correlation between the genetic variations rs7305526 and rs11615756 of nitric oxide synthase 1(NOS1)and the human sleep traits,including insomnia,sleep duration,and clinical quantitative traits related to obstructive sleep apnea(OSA).Methods·The NOS1 gene expression pattern at the whole-brain level using the Allen Human Brain Atlas dataset was analyzed.Subsequently,we performed expression quantitative trait locus(eQTL)analysis to investigate the impact of rs7305526 and rs11615756 on NOS1 gene expression.Regression analysis was conducted to assess the associations between rs7305526 and rs11615756 with insomnia and sleep duration based on the United Kingdom Biobank(UKB)Genome-Wide Association Study(GWAS)dataset.Furthermore,we explored the relationships between rs7305526 and rs11615756 with clinical quantitative traits of OSA,such as respiratory events,oxygen levels,and sleep traits,using clinical monitoring data from the Shanghai Sleep Health Study Cohort(SSHS)based on standard polysomnography(PSG).Results·The NOS1 gene demonstrated elevated levels of expression in various brain regions crucial for regulating sleep,namely the amygdala,basal forebrain,striatum,and thalamus,as well as in the respiratory center,including the mesencephalon and pontine tegmentum.In contrast,the expression level of NOS1 gene was significantly reduced or absent in areas such as the cerebral cortex and cerebellum.Variants rs7305526 and rs11615756 were significantly negatively correlated with the expression levels of NOS1 in the cerebral cortex.Additionally,rs11615756 was also significantly negatively correlated with the expression level of NOS1 in the amygdala.Analysis of the UKB GWAS data revealed that the variant rs7305526 was not significantly associated with either insomnia or sleep duration,while rs11615756 demonstrated a noteworthy negative correlation specifically with sleep duration.Data obtained from the SSHS indicated a significant association between rs7305526 and alterations in clinical quantitative traits of OSA,including lowest pulse blood oxygen saturation(LSpO2),apnea-hypopnea index(AHI),and the ratio of non-rapid eye movement(NREM)stage 2 sleep duration.Although rs11615756 showed a notable negative correlation solely with the quantity of NREM stages 2 and 3,both rs11615756 and rs7305526 showed significant correlations with some respiratory events and oxygen traits after stratification according to the severity of OSA.Conclusion·Genetic variants of NOS1 gene are respectively associated with human sleep duration traits and OSA-related variables,suggesting that NOS1 gene plays a crucial regulatory role in human sleep and clinical quantitative traits of OSA.The regulation of sleep traits by rs7305526(C>A)is independent of its regulation of respiratory events and oxygen traits.

Objective·To explore the correlation between the genetic variations rs7305526 and rs11615756 of nitric oxide synthase 1(NOS1)and the human sleep traits,including insomnia,sleep duration,and clinical quantitative traits related to obstructive sleep apnea(OSA).Methods·The NOS1 gene expression pattern at the whole-brain level using the Allen Human Brain Atlas dataset was analyzed.Subsequently,we performed expression quantitative trait locus(eQTL)analysis to investigate the impact of rs7305526 and rs11615756 on NOS1 gene expression.Regression analysis was conducted to assess the associations between rs7305526 and rs11615756 with insomnia and sleep duration based on the United Kingdom Biobank(UKB)Genome-Wide Association Study(GWAS)dataset.Furthermore,we explored the relationships between rs7305526 and rs11615756 with clinical quantitative traits of OSA,such as respiratory events,oxygen levels,and sleep traits,using clinical monitoring data from the Shanghai Sleep Health Study Cohort(SSHS)based on standard polysomnography(PSG).Results·The NOS1 gene demonstrated elevated levels of expression in various brain regions crucial for regulating sleep,namely the amygdala,basal forebrain,striatum,and thalamus,as well as in the respiratory center,including the mesencephalon and pontine tegmentum.In contrast,the expression level of NOS1 gene was significantly reduced or absent in areas such as the cerebral cortex and cerebellum.Variants rs7305526 and rs11615756 were significantly negatively correlated with the expression levels of NOS1 in the cerebral cortex.Additionally,rs11615756 was also significantly negatively correlated with the expression level of NOS1 in the amygdala.Analysis of the UKB GWAS data revealed that the variant rs7305526 was not significantly associated with either insomnia or sleep duration,while rs11615756 demonstrated a noteworthy negative correlation specifically with sleep duration.Data obtained from the SSHS indicated a significant association between rs7305526 and alterations in clinical quantitative traits of OSA,including lowest pulse blood oxygen saturation(LSpO2),apnea-hypopnea index(AHI),and the ratio of non-rapid eye movement(NREM)stage 2 sleep duration.Although rs11615756 showed a notable negative correlation solely with the quantity of NREM stages 2 and 3,both rs11615756 and rs7305526 showed significant correlations with some respiratory events and oxygen traits after stratification according to the severity of OSA.Conclusion·Genetic variants of NOS1 gene are respectively associated with human sleep duration traits and OSA-related variables,suggesting that NOS1 gene plays a crucial regulatory role in human sleep and clinical quantitative traits of OSA.The regulation of sleep traits by rs7305526(C>A)is independent of its regulation of respiratory events and oxygen traits.

The skin is the first barrier to maintain the stability of internal environment of the body and resist harmful factors of external environment, and is easily damaged because of various external factors. When full-thickness skin defects reach a certain level, it is difficult for the skin to repair itself, so wound dressings are needed to promote wound healing. Seeking an ideal dressing that can promote wound healing has long been a hot research topic. Chitosan is a unique biopolysaccharide polymer with good biocompatibility, biodegradability, antibacterial activity, and thermal stability, which has great potential in the development and application of wound dressings. Based on the introduction of properties of chitosan, this article reviews the role and mechanism of chitosan-based wound dressings in wound healing, and summarizes the hemostatic effect, antibacterial effect, delivery effect, and tissue regeneration promotion effect of chitosan, aiming to provide a certain reference for the research and development of new chitosan-based wound dressings in the future.

Objective:To understand the psychological status and nursing needs of maintenance hemodialysis (MHD) patients and provide reference for clinical targeted nursing.Methods:Using the phenomenological research method, a total of 15 patients with MHD in the First Affiliated Hospital of Zhengzhou University were selected as the research objects by the purposive sampling method, and they were given semi-structured individualized interviews. The Colaizzi 7-step analysis method was used to organize the data, extract the inductive themes and analyze the results.Results:The psychological status of MHD patients was repressed fear, despair and helplessness and acceptance. The nursing needs of MHD patients included disease-related knowledge needs, social support needs and health guidance needs.Conclusions:MHD patients have negative psychology. Medical staff need to understand the psychological status and nursing needs of patients and formulate targeted nursing interventions to meet the actual needs of patients and improve the quality of life of them.