Objective: To examine the causal association and potential mechanisms between bone mineral density in different age groups and primary malignant bone tumor based on two sample Mendelian randomization (MR), so as to provide a reference for the prevention and treatment of primary malignant bone tumor. Methods: The genome-wide association study (GWAS) of bone mineral density was obtained from the GEFOS database,which included 66 628 subjects divided into five age groups (0-15, 15-30, 30-45, 45-60, and >60 years) based on the phases of human bone development. The GWAS of primary malignant bone tumor was sourced from the FinnGen database, including 648 cases and 378 749 controls. Using bone mineral density of five age groups as the exposure and primary malignant bone tumor as the outcome, an MR analysis was performed with the inverse-variance weighted (IVW) method. Sensitivity analysis were conducted using Cochran's Q test, MR-Egger regression, MR-PRESSO test and MR Steiger test. The potential mechanisms underlying the causal association between bone density and primary malignant bone tumors were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results: The MR analysis results showed that there was a negative causal association between bone density and primary malignant bone tumors in the 30-45 age group (OR=0.301, 95%CI: 0.126-0.721). No statistically significant associations between bone density and primary malignant bone tumors were found in the 0-15, 15-30, 45-60, and >60 age groups (all P>0.05). Sensitivity analysis did not detect heterogeneity, pleiotropy (all P>0.05) and reverse causality. KEGG enrichment analysis revealed that genes highly associated with bone density and primary malignant bone tumors were enriched in the mTOR signaling pathway and the Wnt signaling pathway, among which Low Density lipoprotein Receptor Related protein 5 and Wnt Family Member 16 are key regulatory genes. Conclusion The decrease in bone mineral density among individuals aged 30-45 may increase the risk of primary malignant bone tumors through the mTOR signaling pathway and the Wnt signaling pathway.

The aging microenvironment, as a key driver of tumorigenesis and progression, plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype (SASP). SASP consists of a variety of interleukins, chemokines, proteases, and growth factors. It initially induces surrounding cells to enter a state of senescence through paracrine mechanisms, thereby creating a sustained inflammatory stimulus and signal amplification effect within the tissue microenvironment. Furthermore, these secreted factors activate key signaling pathways such as NF-κB, cGAS-STING, and mTOR, which regulate the expression of immune-related molecules (such as PD-L1) and promote the recruitment of immunosuppressive cells, including regulatory T cells and myeloid-derived suppressor cells. This process ultimately contributes to the formation of an immunosuppressive tumor microenvironment. Furthermore, the article explores potential anti-tumor immunotherapy strategies targeting SASP and its associated molecular mechanisms, including approaches to inhibit SASP secretion or eliminate senescent cells. Although these strategies have shown promise in certain tumor models, the high heterogeneity among tumor types may result in varied responses to SASP-targeted therapies. This highlights the need for further research into adaptive stratification and personalized treatment approaches. Targeting immune regulatory mechanisms in the aging microenvironment-particularly SASP-holds great potential for advancing future anti-tumor therapies.

Dysfunction of the interoceptive system is recognized as an important component of clinical symptoms, including anxiety, depression, psychosis, and other mental disorders. Non-invasive neuromodulation is an emerging clinical intervention approach, and over the past decade, research on non-invasive neuromodulation aimed at regulating interoception has rapidly developed. This review first outlines the pathways of interoceptive signals and assessment methods, then summarizes the interoceptive abnormalities in psychiatric disorders and current studies for non-invasive neuromodulation targeting interoception, including intervention modes, target sites, interoceptive measures, and potential neurobiological mechanisms. Finally, we discuss significant research challenges and future directions.
Humans ; Interoception/physiology* ; Mental Disorders/therapy*

The Occupational Classification Dictionary of the People's Republic of China (2015 Edition) has added a new occupation type, Medical Nursing Assistants, aiming to meet the strong demand for medical care in the context of the aging population in China.In order to standardize the services of medical nursing assistants for the elderly in home and community settings and contribute to healthy aging, the National Health Commission issued the " Service Standards for Medical Nursing Assistants of Older Adults in Home and Community" ( WS/ T 803—2022) on September 28, 2022.The standards regulate the service processes, service items and requirements, as well as service evaluation and improvement for elderly medical nursing assistants.The interpretation of the standard's formulation background, the compilation process, and the standard's content are as follows.

Objective: To investigate the causal association between amino acids and the primary malignant bone tumor and its underlying mechanism. Methods: Genome-wide association study (GWAS) data of glycine, serine, arginine, glutamine, methionine, and leucine was sourced from the IEU OpenGWAS database and the GWAS Catalog. GWAS data of primary malignant bone tumor were obtained from the FinnGen database. Using each of the six amino acids as the exposure and primary malignant bone tumor as the outcome, two-sample Mendelian randomization (MR) analysis was performed with the inverse-variance weighted method as the primary approach. Multivariable MR analysis was employed to control for collinearity among amino acids. Sensitivity analyses were conducted using Cochran's Q test, MR-Egger regression and the MR Steiger test. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction network analysis were explored to explore potential mechanisms and identify key genes. Results: MR analysis results indicated a statistically significant causal association between glycine and primary malignant bone tumor (OR=1.719, 95%CI: 1.083-2.728). No significant causal associations were found for the other five amino acids (all P>0.05). Multivariable MR analysis revealed that, after adjusting for the other five amino acids, confirmed a positive causal association between glycine and primary malignant bone tumor (OR=1.512, 95%CI: 1.125-2.031). Sensitivity analyses revealed no significant heterogeneity, horizontal pleiotropy, or reverse causality (all P>0.05). Genes associated with both glycine metabolism and primary malignant bone tumor were enriched in the JAK-STAT signaling pathway, with serine hydroxymethyltransferase 2 (SHMT2) identified as a key gene. Conclusion Higher glycine levels may increase the risk of primary malignant bone tumor via the SHMT2-JAK-STAT pathway.

Objective:To screen the key genetic,diagnostic and therapeutic targets of chronic obstructive pulmonary disease(COPD)patients by using microarray datasets and Mendelian randomization(MR)method,and to provide the evidence for clinical diagnosis and treatment of COPD.Methods:Four COPD gene expression profile datasets were obtained from the Gene Expression Omnibus(GEO)database.The data were processed and normalized using R software,and differentially expressed genes(DEGs)were screened.MR analysis was performed to explore the causal relationship between COPD and expression quantitative trait loci(eQTL),intersection with DEGs was taken to identify potential key targets.Gene Set Enrichment Analysis(GSEA),Gene Ontology(GO)functional enrichment analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were conducted to investigate the functional roles and pathways of the key targets,external datasets were used to validate their expression.Results:A total of 1 571 DEGs were screened,including 820 upregulated genes and 751 downregulated genes.MR analysis identified 286 COPD-related genes,and intersection with DEGs revealed 3 upregulated genes:diacylglycerol kinase gamma(DGKG),neurofilament heavy polypeptide(NEFH),and Fc receptor like B(FCRLB);and 6 downregulated genes:STEAP4 metalloreductase(STEAP4),pleckstrin homology domain containing family F member 2(PLEKHF2),CD3d molecule(CD3D),transgelin 2(TAGLN2),tripartite motif containing 22(TRIM22),and ribosomal protein L9(RPL9).The biological function analysis results indicated that these genes were mainly involved in pathways such as iron ion transport into the cells,oxidoreductase activity,primary immunodeficiency,and Th1 and Th2 cell differentiation.The MR analysis results confirmed the causal relationship between these targets and COPD.The external validation results showed that compared with healthy controls,the expression level of FCRLB in COPD samples was significantly increased(P<0.01),while the expression levels of CD3D and RPL9 were significantly decreased(P<0.05 or P<0.01),which was consistent with the MR analysis results,highlighting the reliability of this study.Conclusion:DGKG,NEFH,FCRLB,STEAP4,PLEKHF2,CD3D,TAGLN2,TRIM22,and RPL9 may serve as important regulatory factors and clinical diagnostic/therapeutic targets in the pathogenesis of COPD,providing clues for early screening,diagnosis,and targeted treatment of COPD.

Objective:To investigate the factors influencing the delayed onset of intrapartum fever following epidural labor analgesia and their impact on maternal and neonatal outcomes.Methods:Select parturients who experienced intrapartum fever following labor analgesia(T≥38.0℃,age≥18 years,singleton pregnancy,ASA classification Ⅱ)between January 1,2021,and December 31,2023.Group them based on the median time of intra-partum fever onset after labor analgesia:those with onset times less than the median were classified as the ear-ly-onset fever group,and those with onset times greater than the median were classified as the late-onset fever group.Using univariate and multivariate Logistic regression analysis to explore factors influencing the delay in in-trapartum fever onset and the pregnancy outcomes of the mothers and newborns in both groups.Results:A total of 253 parturients were included,and the time range of onset of intrapartum fever following epidural labor analgesi-a was 1.83-28.42 hours,with a median fever onset time of 8.00 hours.There were 126 cases in the early-onset group and 127 in the late-onset group.Multivariate Logistic regression analysis indicated that primiparous women,artificial membrane rupture,and neonatal birth weight were independent risk factors for delayed fever onset(OR＞1,P＜0.05),whereas the administration of oxytocin prior to labor analgesia was found to be a protective factor(OR＜1,P＜0.05).The late-onset group exhibited higher levels of white blood cells(WBC),C-reactive pro-tein,longer hospital stays,higher hospitalization costs,greater diagnosis rates of chorioamnionitis,higher NICU ad-mission rates,as well as a higher incidence of neonatal pneumonia,for newborns compared to the early-onset group(P＜0.05).Conclusions:Primiparous women,artificial membrane rupture,and higher neonatal birth weight may be associated with delayed onset of intrapartum fever,while oxytocin administration prior to labor analgesia may offer some protective benefit.The later the onset of intrapartum fever,the worse the clinical outcomes for both mother and infants.

Objective To investigate the mechanism underlying the effect of intra-articular injection of ozonated water on cartilage repair in knee osteoarthritis(KOA)rats via the miR-214-3p/nuclear factor(NF)-κB signaling pathway,to provide a theoretical basis for the clinical application of ozonated water.Methods Sixty male Sprague-Dawley rats were divided randomly into ozonated and experimental groups.Rats in the experimental group were further divided randomly into model,ozonated water,ozonated water+AAV-NC,and adeno-associated virus with ozonated water+AAV-miR-214-3p inhibitor groups.The articular cartilage repair status was evaluated after the respective treatments,using articular cartilage surface gross scoring,hematoxylin/eosin staining,and modified Mankin's score.Expression levels of interleukin(IL)-1β,tumor necrosis factor(TNF)-α,and matrix metalloproteinase(MMP)-13 were detected by enzyme-linked immunosorbent assay(ELISA).Protein expression levels of IκB kinase(IKK)β,p65,and phospho(p)-IκBα were detected in cartilage tissues by Western blot,and gene expression levels of IKKβ,p65,IκBα,and miR-214-3p were detected by real-time polymerase chain reaction(RT-PCR).Results Rats in all groups showed different degrees of cartilage damage compared with the control group,and the scores were significantly lower in the ozonated water and ozonated water+AAV-NC groups compared with the ozonated water+AAV-miR-214-3p inhibitor group(P＜0.05).IL-1β,TNF-α,and MMP-13 levels detected by ELISA were significantly lower in cartilage tissues from rats in the ozonated water and ozonated water+AAV-NC groups compared with the model and ozonated water+AAV-miR-214-3p inhibitor groups(P＜0.05).According to RT-PCR,IKKβ and p65 mRNA levels were significantly down-regulated while IκBα mRNA was significantly up-regulated in cartilage tissues from rats in the ozonated water and ozonated water+AAV-NC groups compared with the model and ozonated water+AAV-miR-214-3p inhibitor groups(P＜0.05).Similarly,IKKβ,p65,and p-IκBα protein expression levels detected by Western blot were significantly down-regulated while IκBα protein expression levels were up-regulated in cartilage tissues from rats in the ozonated water and ozonated water+AAV-NC groups compared with the model and ozonated water+AAV-miR-214-3p inhibitor groups(P＜0.05).Conclusions Ozone hydrotherapy significantly ameliorated cartilage damage in KOA rats,possibly via inhibiting activation of the NF-κB signaling pathway through up-regulation of miR-214-3p expression and promoting cartilage repair in KOA rats.

Objective·To investigate the longitudinal changes in amygdala and hippocampal subfield volumes before and after transcranial magnetic stimulation(TMS)treatment in patients with major depressive disorder(MDD)and explore their correlation with the antidepressant and anxiolytic efficacy of TMS.Methods·A total of 58 patients diagnosed with MDD at Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,were included in this study between January 2018 and August 2023.Clinical depressive and anxiety symptoms were assessed by using the Hamilton Depression Scale(HAMD),Montgomery-Asberg Depression Rating Scale(MADRS),and Hamilton Anxiety Scale(HAMA)at baseline and post-TMS treatment.Patients underwent a baseline magnetic resonance imaging(MRI)scan followed by TMS treatment targeting the left dorsolateral prefrontal cortex(DLPFC)at a frequency of 10 Hz,totaling 20 sessions.A follow-up MRI scan was conducted on the same day the TMS treatment concluded.Amygdala and hippocampal subfield volumes were segmented and calculated by using FreeSurfer v6.0.0 software.Longitudinal changes in the subfield volumes were analyzed with two-way analysis of variance.Controlling for age,sex,and intracranial volume,partial correlation analysis was conducted between subfield volumes and baseline clinical scores.The association between the rate of volume change in brain regions with significant volume changes and symptom improvement(reduction in HAMD,MADRS,and HAMA scores)was evaluated.Results·Following TMS treatment,a significant increase in the volume of the right amygdala central nucleus was observed(t=-2.441,P=0.018).While the volumes of bilateral hippocampal fimbria decreased,the volumes of most hippocampal subfield and the total hippocampus increased(P<0.05).No significant correlations were found between baseline amygdala or hippocampal subfield volumes and clinical depressive and anxiety symptoms.However,only in patients who responded effectively to TMS treatment,a positive correlation was found between the volume change rate of the left hippocampal tail and reductions in anxiety symptoms(HAMA:r=0.334,P=0.044).Conclusion·High-frequency TMS targeting the left DLPFC may induce volume increases in the right amygdala central nucleus and specific hippocampal subfields.Additionally,the volume change rate of the left hippocampal tail is associated with anti-anxiety effects in TMS responders,suggesting that high-frequency TMS targeting the left DLPFC may induce neuroplastic changes in the central nucleus of the right amygdala and key subfields of the hippocampus.

Objective·To investigate the longitudinal changes in amygdala and hippocampal subfield volumes before and after transcranial magnetic stimulation(TMS)treatment in patients with major depressive disorder(MDD)and explore their correlation with the antidepressant and anxiolytic efficacy of TMS.Methods·A total of 58 patients diagnosed with MDD at Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,were included in this study between January 2018 and August 2023.Clinical depressive and anxiety symptoms were assessed by using the Hamilton Depression Scale(HAMD),Montgomery-Asberg Depression Rating Scale(MADRS),and Hamilton Anxiety Scale(HAMA)at baseline and post-TMS treatment.Patients underwent a baseline magnetic resonance imaging(MRI)scan followed by TMS treatment targeting the left dorsolateral prefrontal cortex(DLPFC)at a frequency of 10 Hz,totaling 20 sessions.A follow-up MRI scan was conducted on the same day the TMS treatment concluded.Amygdala and hippocampal subfield volumes were segmented and calculated by using FreeSurfer v6.0.0 software.Longitudinal changes in the subfield volumes were analyzed with two-way analysis of variance.Controlling for age,sex,and intracranial volume,partial correlation analysis was conducted between subfield volumes and baseline clinical scores.The association between the rate of volume change in brain regions with significant volume changes and symptom improvement(reduction in HAMD,MADRS,and HAMA scores)was evaluated.Results·Following TMS treatment,a significant increase in the volume of the right amygdala central nucleus was observed(t=-2.441,P=0.018).While the volumes of bilateral hippocampal fimbria decreased,the volumes of most hippocampal subfield and the total hippocampus increased(P<0.05).No significant correlations were found between baseline amygdala or hippocampal subfield volumes and clinical depressive and anxiety symptoms.However,only in patients who responded effectively to TMS treatment,a positive correlation was found between the volume change rate of the left hippocampal tail and reductions in anxiety symptoms(HAMA:r=0.334,P=0.044).Conclusion·High-frequency TMS targeting the left DLPFC may induce volume increases in the right amygdala central nucleus and specific hippocampal subfields.Additionally,the volume change rate of the left hippocampal tail is associated with anti-anxiety effects in TMS responders,suggesting that high-frequency TMS targeting the left DLPFC may induce neuroplastic changes in the central nucleus of the right amygdala and key subfields of the hippocampus.