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*

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 clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes.Methods:The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up.Results:Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features.Conclusions:Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.

Objective·To analyze the epidemiological characteristics of risk factors for cardiovascular diseases and malignant tumors based on the Shanghai community elderly cohort.Methods·The study subjects were selected from the Shanghai community elderly cohort established from February to August 2019,with a total of 17 948 people.The study subjects were divided into 4 groups according to self-reported presence or absence of tumors and/or cardiovascular diseases during the baseline survey:tumor-free and non-cardiovascular disease group,single cardiovascular disease group,single tumor group and tumor cardiovascular disease co-occurrence group.The differences among the four groups of subjects were collected and compared in terms of demographic characteristics and physiological indicators,daily living habits(smoking,drinking tea,drinking coffee,drinking carbonated drink,drinking alcohol,sedentary time,physical activity level and sleep quality),past medical history,psychological status(depression and anxiety)and dietary compliance.Results·Among the study subjects,60.1%of tumor patients were complicated with cardiovascular diseases.The differences among the four groups of subjects in age,gender,educational level,pre-retirement occupation,waist circumference,hip circumference and body mass index were statistically significant(all P<0.05).Compared with the tumor-free and non-cardiovascular disease group,the single cardiovascular disease group,single tumor group and tumor cardiovascular disease co-occurrence group all exhibited lower proportions of smoking and high physical activity levels(all P<0.05),and higher proportion of sedentary time exceeding 4 h/d and poor sleep quality(all P<0.05);the proportion of subjects with past medical histories including hyperlipidemia,peripheral vascular disease,endocrine system disease,respiratory system disease,urinary system disease and digestive system disease of the single cardiovascular disease group and the tumor cardiovascular disease co-occurrence group was higher(all P<0.05),and the proportion of subjects with depression and anxiety was also higher(all P<0.05).Furthermore,compared with the tumor-free and non-cardiovascular disease group,the single cardiovascular disease group had lower compliance rates of poultry,fish,fruit and liquid milk(all P<0.05).Among the four groups,only the compliance rate of vegetable intake exceeded 50%,while the compliance rates of poultry,fish,fruit,liquid milk and tubers were all below 20%.Conclusion·In the elderly population of Shanghai communities,over half of malignant tumor patients are concomitant with cardiovascular diseases.Unhealthy daily habits are prevalent among those with cardiovascular diseases,tumors and tumor-cardiovascular disease co-occurrence.The intake of many foods in the elderly of the community do not reach the levels recommended by Chinese Dietary Guidelines.

Objective To investigate the correlation between high-resolution computed tomograohy(HRCT)features and thera-peutic effect in patient with non-tuberculous mycobacteria pulmonary disease(NTM-PD).Methods A total of 225 NTM-PD patients were divided into curative group and non-curative group according to the efficacy criteria,and the clinical and HRCT features between the two groups were compared.Correlation analysis and logistic regression analysis were used to screen the risk factors for potential poor efficacy,and their predictive value was evaluated by the receiver operating characteristic(ROC)curve.Results The proportion of cavities,the number of nodules and bronchiectasis involving lung lobes in the non-curative group were significantly higher than those in the curative group,while the body mass index(BMI)was significantly lower than that in the curative group.The distribution of non-tuberculous mycobacteria(NTM)strains,cavities,the number of nodules involving lung lobes,and the number of bronchiecta-sis involving lung lobes were positively correlated with poor efficacy,while BMI was negatively correlated with poor efficacy(P＜0.05).The distribution of NTM strains,the number of nodules and bronchiectasis involving lung lobes were independent risk factors for poor efficacy(P＜0.05).Cavities,the number of nodules involving lung lobes,and the number of bronchiectasis involving lung lobes alone or in combination had high efficacy in predicting poor efficacy,with the highest prediction value of the three combined model[area under the curve(AUC)=0.819;95％confidence interval(CI)0.762-0.876].Conclusion The combined model based on cavities,the number of nodules involving lung lobes,and the number of bronchiectasis involving lung lobes has the highest effi-ciency in predicting poor efficacy in NTM-PD patients.

【Objective】 To evaluate the predictive value of isoform [-2] proprostate-specific antigen, p2 PSA (p2PSA) and its derived indexes for prostate cancer in a Chinese cohort with PSA 4-20 ng/mL. 【Methods】 A total of 139 males scheduled for biopsy were enrolled in the prospective study from Nov.2021 to Jun.2022. The total PSA (tPSA), free PSA (fPSA), fPSA/tPSA (f/t) and p2PSA were collected, and the percentage of p2PSA(%p2PSA) and prostate health index(PHI) were calculated. The predictive value of p2PSA and its derived indexes were compared with traditional indexes with receiver operating characteristic (ROC) curve and Logistic analysis. 【Results】 Prostate cancer was found in 54 cases (38.8%). There were significant statistical differences in tPSA(10.68 vs.8.14, P=0.021), f/t(0.13 vs.0.16, P=0.006), p2PSA(30.25 vs.19.81, P<0.001), %p2PSA(21.52 vs.13.15, P<0.001) and PHI(64.3vs.38.2, P<0.001) between prostate cancer patients and non-prostate cancer patients. The area under the ROC curve (AUC) of tPSA, fPSA, %fPSA, p2PSA, %p2PSA and PHI were 0.63, 0.51, 0.63, 0.71, 0.73, and 0.80, respectively. The inclusion of %p2PSA and PHI significantly increased the prediction efficiency of the basic prediction model (AUCbase+PHI=0.81, AUCbase+%p2PSA=0.78, AUCbase=0.67). With 35 as the recommended cut-off value of PHI, the incidence of meaningless puncture was reduced by 25.8%(36/139). 【Conclusion】 The application of p2PSA and its derived indexes have good predictive value for patients with PSA 4-20 ng/mL. The combined detection of %p2PSA and PHI can significantly increase the detection efficiency of prostate cancer and reduce the incidence of meaningless prostate puncture by 25.8%.

Objective:To evaluate the application value of patient-based real-time quality control (PBRTQC) algorithms in intralaboratory comparison between various hematology analyzers.Method:From April 1 st 2020 to March 31 th 2021, data of white blood cell (WBC) counts and daily comparison results of fresh venous blood, measured by five hematology analyzers, were collected at the Department of Laboratory Medicine in Hebei Children′s Hospital. First, the professional intelligent PBRTQC software system was applied to conduct the parameter setting, program establishment, and performance verification. Three concentration ranges of WBC were selected, low concentration (2.5-4.5)×10 9/L, medium concentration (6.0-8.0)×10 9/L and high concentration (12.0-14.0)×10 9/L for the comparison. Next, WBC counts were calculated with both of the EWMA and median methods, the results were then analyzed by PBRTQC using the module of"intralaboratory comparison of hematology analyzers". Finally, bias of intralaboratory comparison among various hematology analyzers analyzed by means of EWMA and daily comparison results of fresh venous blood were compared. Based on the standard of WS/T 406-2012,allowable error ±7.50% in WBC counts was set as the relative bias standard among different instruments. Results:(1) A total of 38 313 sample results were included, there were 70 warning results out of these samples based on the EWMA quality control method established on the data of patients with white blood cell count in our laboratory, with an early warning rate of 0.183‰, a probability of error detection of 100%, and a probability of false loss of control of 0. EWMA quality control efficiency met the quality objectives. (2) In the comparison monitoring of the results of 5 blood cell analyzers at high concentrations, the coincidence rate between EWMA and median method were both 100% (46/46) in weekly and monthly comparison, and EWMA could maintain a relatively stable monitoring efficiency in daily comparison. (3) In the selected natural month, the consistency rate between EWMA method and fresh blood comparison method was 95.24% (20/21).Conclusion:PBRTQC can be used as a valuable supplementary tool of IQC to continuously and effectively monitor the consistency of data derived from intralaboratory hematology analyzers with different bands and types, which can not only reduce the risk of quality and operating costs, but also improve the efficiency of laboratory management.