OBJECTIVES: To investigate the associations between Tau protein deposition and brain biochemical metabolites detected by proton magnetic resonance spectroscopy (¹H-MRS) in patients with advanced Alzheimer's disease (AD). METHODS: From April, 2022 to December, 2024, 64 Tau-positive AD patients and 29 healthy individuals underwent ¹⁸F-APN-1607 PET/MR and simultaneously acquired multi-voxel ¹H-MRS in the Department of Nuclear Medicine, Nanjing First Hospital. Visual analysis and voxel-based analysis of PET/MR data were performed to investigate the Tau protein deposition patterns in AD patients. Valid voxels within the ¹H-MRS field of view were selected, and their standardized uptake value ratio (SUVr) in PET and metabolite levels of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), NAA/Cr, and Cho/Cr were recorded. The Tau-positive (Tau⁺) voxels and Tau-negative (Tau^-) voxels of the AD patients were compared for PET and ¹H-MRS parameters, and the correlations between the metabolites and Tau PET SUVr within Tau⁺ voxels were analyzed. RESULTS: Significant Tau protein deposition were observed in the AD patients, involving mainly the bilateral frontal lobes (30.07%), parietal lobes (29.96%), temporal lobes (21.07%), and occipital lobes (15.89%). A total of 1422 valid voxels in AD group (including 994 Tau⁺ and 428 Tau^- voxels) and 814 voxels in the control group were selected. The AD patients showed significantly decreased NAA level and increased SUVr compared with the control group (P<0.05). Subgroup analyses revealed that Tau⁺ voxels had higher SUVr and lower Cr and Cho/Cr than Tau^- voxels (P<0.05). Compared with the control group, Tau⁺ voxels exhibited higher SUVr and lower Cr (P<0.05), while Tau^- voxels showed lower NAA (P=0.004). No significant differences were found in Cho or NAA/Cr among the subgroups (P>0.05). Within Tau⁺ voxels, NAA, Cho, and Cr were negatively correlated with SUVr (P<0.001). CONCLUSIONS The patients with progressive AD have significant Tau protein deposition in the brain, which is correlated with alterations in metabolite levels. Decreased NAA is more prominent in early or pre-tau deposition stages, while Cr changes is more significant in the regions with Tau protein deposition, suggesting the potential of NAA and Cr as biomarkers for Tau protein deposition in AD for disease monitoring and treatment evaluation.
Humans ; Alzheimer Disease/diagnostic imaging* ; Aspartic Acid/metabolism* ; tau Proteins/metabolism* ; Creatine/metabolism* ; Brain/metabolism* ; Biomarkers/metabolism* ; Positron-Emission Tomography ; Male ; Female ; Proton Magnetic Resonance Spectroscopy ; Choline/metabolism* ; Aged ; Middle Aged

Objective:To investigate the mediating effects of medical inquiry ability and attitudes toward aging on the relationship between socioeconomic status and mental health among the elderly.Methods:Utilizing data from the 2021 China General Social Survey(CGSS), a sample of 957 individuals aged 60 years and older was selected for analysis.The influence of each variable was assessed through regression analysis, and the mediating effects were evaluated using the Bootstrap method.Results:The study samples ranged in age from 60 to 95 years, including 479 females and 478 males.Socioeconomic status significantly positively influenced mental health( β=0.208, P<0.001).Additionally, socioeconomic status had a notable positive effect on medical inquiry ability( β=0.244, P<0.001)and attitudes toward aging( β=0.163, P<0.001)among the elderly population.Furthermore, medical inquiry ability positively affected both attitudes toward aging( β=0.158, P<0.001)and mental health( β=0.139, P<0.001).The attitude toward aging also had a significant positive impact on mental health( β=0.216, P<0.001).Notably, both medical inquiry ability and attitudes toward aging served as significant mediators between socioeconomic status and mental health in the elderly, with a total indirect effect value of 0.091(95% CI: 0.063-0.123).The chain mediating effect of medical inquiry ability and pension mentality was also significant, with an effect size of 0.010(95% CI: 0.005-0.017). Conclusions:Enhancing the socioeconomic status of older adults can foster their medical inquiry ability, positively influence their attitudes toward aging, and ultimately contribute to the promotion of their mental health.

Objective:To investigate the effects of 177Lu-prostate specific membrane antigen (PSMA)-I&T combined with poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor (PARPi) fluzoparib on the proliferation and migration of prostate cancer cells and the tumor inhibitory effects. Methods:177Lu-PSMA-I&T was synthesized. Cytotoxicity assay, colony formation assay, 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation assay, Transwell cell migration assay, and terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, flow cytometry were performed to detect apoptosis and cell cycles. 22RV1 tumor-bearing mice models ( n=16) were established, and were randomly divided into 4 groups: control group (no treatment; n=4), fluzoparib monotherapy group (6mg/kg; n=4), 177Lu-PSMA-I&T monotherapy group (14.8MBq; n=4) and combination group (14.8MBq 177Lu-PSMA-I&T+ 6mg/kg fluzoparib; n=4). All mice were treated for 14 d. Tumor volume and body mass changes of tumor-bearing mice were observed and recorded. After the treatment, 18F-FDG PET/CT was performed to evaluate the tumor′s uptake of 18F-FDG. Effects of 177Lu-PSMA-I&T combined with fluzoparib on cell and tumor-bearing mice were observed. One-way analysis of variance and the least significant difference t test were used to analyze the data. Results:At half maximal inhibitory concentrations (IC 50) of 177Lu-PSMA-I&T (13.06MBq/ml) and fluzoparib (72.13μmol/L), compared to the fluzoparib monotherapy group and the 177Lu-PSMA-I&T monotherapy group, the combination treatment significantly enhanced the anti-tumor effect on 22RV1 cells, inhibited the DNA synthesis rate and colony-forming ability of 22RV1 cells, reduced cell migration rate, increased the percentage of DNA damage, resulted in a higher proportion of cells arrested in the G2/M phase and increased the apoptosis rate ( F values: 9.77-162.20, t values: 2.98-21.60, all P<0.05). Compared to the fluzoparib monotherapy group and the 177Lu-PSMA-I&T monotherapy group, the combination treatment resulted in a significant reduction in relative tumor volume (RTV%) 14 d post-administration and markedly decreased 18F-FDG uptake ( F values: 25.28 and 67.42, t values: 4.64-8.61, P values: 0.001-0.009). Conclusion:The combination of 177Lu-PSMA-I&T and fluzoparib can inhibit prostate cancer cell proliferation and migration, suppress tumor growth and metabolism, and demonstrates synergistic effects more effectively.

Objective:This study aims to investigate the impact of socioeconomic status on cognitive function in older adults, while analyzing the mediating role of health-related social determinants.The findings will provide a foundation for the implementation of an active aging strategy.Methods:Utilizing data from the China Health and Retirement Longitudinal Study(CHARLS)2020, this study employed multiple linear regression analysis to investigate the relationship between socioeconomic status and cognitive function among older adults.A multiple mediation model was applied to evaluate the mediating effects of health-related social determinants on the association between socioeconomic status and cognitive function, with these mediation effects assessed using the Bootstrap method.Results:The results of the multiple linear regression analysis indicated that socioeconomic status significantly positively influences cognitive function in older adults.Factors such as younger age, male gender, Han ethnicity, and urban residence were associated with higher cognitive scores.The mediation analysis demonstrated that, of the total effect of socioeconomic status on cognitive function, health status accounted for 1.564%, individual lifestyle for 14.820%, social support networks for 2.719%, living conditions for 1.632%, and other social structural factors for 1.496%.In the multiple mediation model, a total of 17.945% of the effect of socioeconomic status on cognitive function in older adults was jointly mediated by health-related social determinants.Conclusions:Socioeconomic status is a critical determinant of cognitive impairment among older adults in China.To address this issue, comprehensive interventions should be implemented to promote the equitable distribution of economic and social resources, reduce socioeconomic disparities, and mitigate health inequalities, thereby enhancing the overall cognitive function of disadvantaged groups.Preventive measures and strategies aimed at improving health status, encouraging healthy lifestyle choices, strengthening social support networks, enhancing living conditions, and optimizing social structural factors could serve as essential intervention points to improve the cognitive function of older adults with lower socioeconomic status.

Diabetic retinopathy(DR)and diabetic nephropathy(DN)are both microvascular complications associated with diabetes.DR is the most direct pathological manifestation of diabetic microvascular diseases.There is parallelism in the occurrence and progression of DR and DN.The gold standard for diagnosing DN is invasive renal biopsy.DR is a pre-dictor of the occurrence and development of DN,or vice versa.However,the relationship between the two has not yet been clarified.In this article,the correlation between DR and DN was analyzed,aiming to identify common biological markers for both conditions and provide a basis for the prevention,early intervention,and treatment of DN.

Diabetic retinopathy(DR)and diabetic nephropathy(DN)are both microvascular complications associated with diabetes.DR is the most direct pathological manifestation of diabetic microvascular diseases.There is parallelism in the occurrence and progression of DR and DN.The gold standard for diagnosing DN is invasive renal biopsy.DR is a pre-dictor of the occurrence and development of DN,or vice versa.However,the relationship between the two has not yet been clarified.In this article,the correlation between DR and DN was analyzed,aiming to identify common biological markers for both conditions and provide a basis for the prevention,early intervention,and treatment of DN.

Objective:To investigate the mediating effects of medical inquiry ability and attitudes toward aging on the relationship between socioeconomic status and mental health among the elderly.Methods:Utilizing data from the 2021 China General Social Survey(CGSS), a sample of 957 individuals aged 60 years and older was selected for analysis.The influence of each variable was assessed through regression analysis, and the mediating effects were evaluated using the Bootstrap method.Results:The study samples ranged in age from 60 to 95 years, including 479 females and 478 males.Socioeconomic status significantly positively influenced mental health( β=0.208, P<0.001).Additionally, socioeconomic status had a notable positive effect on medical inquiry ability( β=0.244, P<0.001)and attitudes toward aging( β=0.163, P<0.001)among the elderly population.Furthermore, medical inquiry ability positively affected both attitudes toward aging( β=0.158, P<0.001)and mental health( β=0.139, P<0.001).The attitude toward aging also had a significant positive impact on mental health( β=0.216, P<0.001).Notably, both medical inquiry ability and attitudes toward aging served as significant mediators between socioeconomic status and mental health in the elderly, with a total indirect effect value of 0.091(95% CI: 0.063-0.123).The chain mediating effect of medical inquiry ability and pension mentality was also significant, with an effect size of 0.010(95% CI: 0.005-0.017). Conclusions:Enhancing the socioeconomic status of older adults can foster their medical inquiry ability, positively influence their attitudes toward aging, and ultimately contribute to the promotion of their mental health.

Objective:To investigate the effects of 177Lu-prostate specific membrane antigen (PSMA)-I&T combined with poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor (PARPi) fluzoparib on the proliferation and migration of prostate cancer cells and the tumor inhibitory effects. Methods:177Lu-PSMA-I&T was synthesized. Cytotoxicity assay, colony formation assay, 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation assay, Transwell cell migration assay, and terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, flow cytometry were performed to detect apoptosis and cell cycles. 22RV1 tumor-bearing mice models ( n=16) were established, and were randomly divided into 4 groups: control group (no treatment; n=4), fluzoparib monotherapy group (6mg/kg; n=4), 177Lu-PSMA-I&T monotherapy group (14.8MBq; n=4) and combination group (14.8MBq 177Lu-PSMA-I&T+ 6mg/kg fluzoparib; n=4). All mice were treated for 14 d. Tumor volume and body mass changes of tumor-bearing mice were observed and recorded. After the treatment, 18F-FDG PET/CT was performed to evaluate the tumor′s uptake of 18F-FDG. Effects of 177Lu-PSMA-I&T combined with fluzoparib on cell and tumor-bearing mice were observed. One-way analysis of variance and the least significant difference t test were used to analyze the data. Results:At half maximal inhibitory concentrations (IC 50) of 177Lu-PSMA-I&T (13.06MBq/ml) and fluzoparib (72.13μmol/L), compared to the fluzoparib monotherapy group and the 177Lu-PSMA-I&T monotherapy group, the combination treatment significantly enhanced the anti-tumor effect on 22RV1 cells, inhibited the DNA synthesis rate and colony-forming ability of 22RV1 cells, reduced cell migration rate, increased the percentage of DNA damage, resulted in a higher proportion of cells arrested in the G2/M phase and increased the apoptosis rate ( F values: 9.77-162.20, t values: 2.98-21.60, all P<0.05). Compared to the fluzoparib monotherapy group and the 177Lu-PSMA-I&T monotherapy group, the combination treatment resulted in a significant reduction in relative tumor volume (RTV%) 14 d post-administration and markedly decreased 18F-FDG uptake ( F values: 25.28 and 67.42, t values: 4.64-8.61, P values: 0.001-0.009). Conclusion:The combination of 177Lu-PSMA-I&T and fluzoparib can inhibit prostate cancer cell proliferation and migration, suppress tumor growth and metabolism, and demonstrates synergistic effects more effectively.

Objective:This study aims to investigate the impact of socioeconomic status on cognitive function in older adults, while analyzing the mediating role of health-related social determinants.The findings will provide a foundation for the implementation of an active aging strategy.Methods:Utilizing data from the China Health and Retirement Longitudinal Study(CHARLS)2020, this study employed multiple linear regression analysis to investigate the relationship between socioeconomic status and cognitive function among older adults.A multiple mediation model was applied to evaluate the mediating effects of health-related social determinants on the association between socioeconomic status and cognitive function, with these mediation effects assessed using the Bootstrap method.Results:The results of the multiple linear regression analysis indicated that socioeconomic status significantly positively influences cognitive function in older adults.Factors such as younger age, male gender, Han ethnicity, and urban residence were associated with higher cognitive scores.The mediation analysis demonstrated that, of the total effect of socioeconomic status on cognitive function, health status accounted for 1.564%, individual lifestyle for 14.820%, social support networks for 2.719%, living conditions for 1.632%, and other social structural factors for 1.496%.In the multiple mediation model, a total of 17.945% of the effect of socioeconomic status on cognitive function in older adults was jointly mediated by health-related social determinants.Conclusions:Socioeconomic status is a critical determinant of cognitive impairment among older adults in China.To address this issue, comprehensive interventions should be implemented to promote the equitable distribution of economic and social resources, reduce socioeconomic disparities, and mitigate health inequalities, thereby enhancing the overall cognitive function of disadvantaged groups.Preventive measures and strategies aimed at improving health status, encouraging healthy lifestyle choices, strengthening social support networks, enhancing living conditions, and optimizing social structural factors could serve as essential intervention points to improve the cognitive function of older adults with lower socioeconomic status.

Objective:To investigate the mediating effect of social interaction on the relationship between internet use and the health status of the elderly.The findings of this research can potentially contribute new insights into improving the health status of the elderly population.Methods:Based on the data from the Chinese General Social Survey(CGSS)in 2021, a total of 2 675 elderly individuals aged 60 and above were included in the study.The researchers analyzed the linear regression relationship between Internet use, social interaction, and the health status of the elderly using a hierarchical regression model.Additionally, a mediation effect test was conducted using the Bootstrap test.Furthermore, heterogeneity analysis of the mediation effect was performed considering factors such as gender, place of residence, working conditions, and physical exercise among the elderly participants.Results:The total effect value was 0.170.The direct effect of Internet use on the health status of older adults was 0.160(95% CI: 0.078-0.240), accounting for 93.66% of the effect value.The indirect effect of social interaction was 0.011(95% CI: 0.003-0.021), accounting for 6.34% of the effect value.The mediating effect of social interaction on the health status of older adults varied among different groups.Among female elderly, rural elderly, elderly who are currently unemployed, and those who are physically active, the mediating effects were 5.16%, 7.86%, 10.18%, and 9.91%, respectively. Conclusions:The impact of internet use and social interaction on the health status of the elderly is notably positive.Additionally, social interaction partially mediates the relationship between internet use and the health status of the elderly.