Objective:To investigate whether there is an association between the total dose of breast cancer radiotherapy, the mean dose of radiation field involving the heart and its substructures, and the long-term incidence of coronary heart disease (CHD) in patients.Methods:A retrospective analysis was conducted on 1125 patients with breast cancer who received radiotherapy with radiation fields involving the hear at Beijing Hospital from January 2009 to June 2022. The heart and its substructures of 54 patients were manually delineated, trained an automatic delineation model, and applied this model to the original radiotherapy planning images to automatically extract dosimetric parameters for the heart and substructures in the original plan. Based on the follow-up results, 1125 breast cancer patients were categorized into the CHD event group ( n=19) and non-event group ( n=1106). Wilcoxon rank-sum test, Chi-square test and adjustment for confounding factors using inverse probability weighting were used to compare the mean radiation dose received by the heart and its substructures, age at presentation, history of smoking, history of alcohol consumption, history of hypertension, and history of diabetes between two groups. The influencing factors of CHD were analyzed by univariate and multivariate logistic regression models. Results:The mean heart dose ( P=0.035), mean dose of right atrium ( P=0.049), right coronary artery ( P=0.013), septum ( P=0.045), and right ventricle ( P=0.039) of the event group were higher than that of the non-event group, and the differences were statistically significant. History of alcohol consumption was an independent risk factor for long-term CHD events in the breast cancer patients ( OR=7.35,95% CI: 1.56-25.58, P=0.004). After adjusting for confounding factors using inverse probability weighting, age at presentation was an independent risk factor for long-term CHD events ( OR=1.03, 95% CI: 1.01-1.05, P=0.004). Conclusions:In the breast cancer population with traditional high-risk factors of CHD receiving radiotherapy, the possibility of CHD probably remains high even if the dose of radiation field involving the heart and its substructures is low. Compared to traditional risk factors of CHD, the mean dose to the heart and its substructures in the radiation field of breast cancer patients exerts less impact on the occurrence of CHD after radiotherapy.

Objective:To understand the latent categories of apathy in young and middle-aged patients with hemorrhagic stroke and analyze the relationship between these categories and disability acceptance, providing a theoretical basis for targeted interventions.Methods:A convenience sampling method was used to select young and middle-aged patients with hemorrhagic stroke hospitalized at Huai′an First Hospital Affiliated to Nanjing Medical University between September 2020 and September 2023. A general information questionnaire, the Apathy Evaluation Scale-Clinician Administered, and the Acceptance of Disability Scale Revised were used for a cross-sectional survey. Latent profile analysis was conducted using Mplus 8.7 software to categorize apathy in these patients, and differences in disability acceptance among the categories were compared.Results:A total of 210 questionnaires were distributed and 203 valid questionnaires were collected. Among 203 patients were included, with 112 males and 91 females, aged 30-59 (47.60 ± 8.51) years old. The apathy score was (46.66 ± 8.78) points, and three latent categories were identified: "high active ability-low apathy" (26.1%, 53/203), "high social ability-moderate apathy" (28.6%, 58/203), and "generally high apathy" (45.3%, 92/203). The total disability acceptance scores for the three categories were (78.19 ± 13.30), (69.50 ± 11.01), and (60.86 ± 14.00) points, respectively, with statistically significant differences ( F=30.39, P<0.01). Conclusions:Apathy in young and middle-aged patients with hemorrhagic stroke can be categorized into three latent profiles, with differences in disability acceptance among the categories. Targeted management and interventions should be developed based on these homogeneous groups to improve disability acceptance.

Objective:To explore latent categories of trajectories in intrinsic capacity in elderly hemodialysis patients and to analyze their influencing factors.Methods:Elderly hemodialysis patients in the Blood Purification Center of Beijing Tongren Hospital affiliated with Capital Medical University from September 2022 to January 2023, were selected for the study using a convenience sampling method. A baseline survey was conducted using the General Information Questionnaire, Hemodialysis Self-Management Instrument, Social Environmental Factor Scale, and Intrinsic Capacity Scale. The Intrinsic Capacity Scale was used to investigate the intrinsic capacity of patients at 6 and 12 months after baseline. The latent class growth model was used to identify latent categories of intrinsic capacity trajectories of elderly hemodialysis patients. Ordered multiclass Logistic regression was used to analyze the influencing factors of latent categories.Results:A total of 317 elderly hemodialysis patients were investigated at baseline, and finally, 309 completed follow-ups. Among the 309 elderly hemodialysis patients, the trajectory of intrinsic capacity was categorized into a low-level slow-decline group (26.2%, 81/309) , a medium-level smooth-decline group (39.8%, 123/309) , and a high-level slow-decline group (34.0%, 105/309) . Ordered multiclass Logistic regression analysis showed that gender, age, mode of residence, per capita monthly income, type of dialyzer, C-reactive protein, score of hemodialysis self-management scale, housing conditions score, transportation condition score, and environmental condition score were the influencing factors of the latent categories of the trajectory in intrinsic capacity of elderly hemodialysis patients, and the difference was statistically significant ( P<0.05) . Conclusions:There is population heterogeneity in the intrinsic capacity trajectory of elderly hemodialysis patients. Healthcare professionals can provide targeted interventions based on the factors influencing the trajectory.

Objective:To investigate the current status and trajectory of intrinsic capacity in community-dwelling older adults and to analyze its influencing factors.Methods:A longitudinal study was conducted from September 2022 to March 2024. A total of 360 older adults were selected by convenience sampling from the Desheng community, Xicheng District of Beijing City and Liucun Community of Xingtai City, Hebei Province. The Intrinsic Capacity Assessment Scale and the Influencing Factors Questionnaire were administered at three-time points: baseline (T1), 6 months (T2), and 12 months (T3). Binary Logistic regression analysis revealed that age, grip strength, the number of geriatric syndromes, and types of social activities were significant influencing factors of intrinsic capacity trajectories in community-dwelling older adults ( P<0.05) . Results:A total of 360 participants were assessed at T1, with 58 and 30 lost to follow-up at T2 and T3, development respectively. Ultimately, 272 older adults completed the follow-up. The growth mixture modeling identified two trajectory types: a high-score stable group (92.3%, 251/272) and a low-score declining group (7.7%, 21/272). Binary Logistic regression analysis showed that age, grip strength, number of geriatric syndromes, and types of social activities were influencing factors of intrinsic capacity trajectories in community-dwelling older adults ( P<0.05) . Conclusions:Intrinsic capacity development trajectories in community-dwelling older adults are heterogeneous. Healthcare professionals should focus on older adults with advanced age, lower grip strength, more geriatric syndromes, and fewer types of social activities to assess and manage their intrinsic capacity and formulate targeted interventions at an early stage.

Objective:To understand the latent categories of apathy in young and middle-aged patients with hemorrhagic stroke and analyze the relationship between these categories and disability acceptance, providing a theoretical basis for targeted interventions.Methods:A convenience sampling method was used to select young and middle-aged patients with hemorrhagic stroke hospitalized at Huai′an First Hospital Affiliated to Nanjing Medical University between September 2020 and September 2023. A general information questionnaire, the Apathy Evaluation Scale-Clinician Administered, and the Acceptance of Disability Scale Revised were used for a cross-sectional survey. Latent profile analysis was conducted using Mplus 8.7 software to categorize apathy in these patients, and differences in disability acceptance among the categories were compared.Results:A total of 210 questionnaires were distributed and 203 valid questionnaires were collected. Among 203 patients were included, with 112 males and 91 females, aged 30-59 (47.60 ± 8.51) years old. The apathy score was (46.66 ± 8.78) points, and three latent categories were identified: "high active ability-low apathy" (26.1%, 53/203), "high social ability-moderate apathy" (28.6%, 58/203), and "generally high apathy" (45.3%, 92/203). The total disability acceptance scores for the three categories were (78.19 ± 13.30), (69.50 ± 11.01), and (60.86 ± 14.00) points, respectively, with statistically significant differences ( F=30.39, P<0.01). Conclusions:Apathy in young and middle-aged patients with hemorrhagic stroke can be categorized into three latent profiles, with differences in disability acceptance among the categories. Targeted management and interventions should be developed based on these homogeneous groups to improve disability acceptance.

Objective:To explore latent categories of trajectories in intrinsic capacity in elderly hemodialysis patients and to analyze their influencing factors.Methods:Elderly hemodialysis patients in the Blood Purification Center of Beijing Tongren Hospital affiliated with Capital Medical University from September 2022 to January 2023, were selected for the study using a convenience sampling method. A baseline survey was conducted using the General Information Questionnaire, Hemodialysis Self-Management Instrument, Social Environmental Factor Scale, and Intrinsic Capacity Scale. The Intrinsic Capacity Scale was used to investigate the intrinsic capacity of patients at 6 and 12 months after baseline. The latent class growth model was used to identify latent categories of intrinsic capacity trajectories of elderly hemodialysis patients. Ordered multiclass Logistic regression was used to analyze the influencing factors of latent categories.Results:A total of 317 elderly hemodialysis patients were investigated at baseline, and finally, 309 completed follow-ups. Among the 309 elderly hemodialysis patients, the trajectory of intrinsic capacity was categorized into a low-level slow-decline group (26.2%, 81/309) , a medium-level smooth-decline group (39.8%, 123/309) , and a high-level slow-decline group (34.0%, 105/309) . Ordered multiclass Logistic regression analysis showed that gender, age, mode of residence, per capita monthly income, type of dialyzer, C-reactive protein, score of hemodialysis self-management scale, housing conditions score, transportation condition score, and environmental condition score were the influencing factors of the latent categories of the trajectory in intrinsic capacity of elderly hemodialysis patients, and the difference was statistically significant ( P<0.05) . Conclusions:There is population heterogeneity in the intrinsic capacity trajectory of elderly hemodialysis patients. Healthcare professionals can provide targeted interventions based on the factors influencing the trajectory.

Objective:To investigate the current status and trajectory of intrinsic capacity in community-dwelling older adults and to analyze its influencing factors.Methods:A longitudinal study was conducted from September 2022 to March 2024. A total of 360 older adults were selected by convenience sampling from the Desheng community, Xicheng District of Beijing City and Liucun Community of Xingtai City, Hebei Province. The Intrinsic Capacity Assessment Scale and the Influencing Factors Questionnaire were administered at three-time points: baseline (T1), 6 months (T2), and 12 months (T3). Binary Logistic regression analysis revealed that age, grip strength, the number of geriatric syndromes, and types of social activities were significant influencing factors of intrinsic capacity trajectories in community-dwelling older adults ( P<0.05) . Results:A total of 360 participants were assessed at T1, with 58 and 30 lost to follow-up at T2 and T3, development respectively. Ultimately, 272 older adults completed the follow-up. The growth mixture modeling identified two trajectory types: a high-score stable group (92.3%, 251/272) and a low-score declining group (7.7%, 21/272). Binary Logistic regression analysis showed that age, grip strength, number of geriatric syndromes, and types of social activities were influencing factors of intrinsic capacity trajectories in community-dwelling older adults ( P<0.05) . Conclusions:Intrinsic capacity development trajectories in community-dwelling older adults are heterogeneous. Healthcare professionals should focus on older adults with advanced age, lower grip strength, more geriatric syndromes, and fewer types of social activities to assess and manage their intrinsic capacity and formulate targeted interventions at an early stage.

Objective:To investigate whether there is an association between the total dose of breast cancer radiotherapy, the mean dose of radiation field involving the heart and its substructures, and the long-term incidence of coronary heart disease (CHD) in patients.Methods:A retrospective analysis was conducted on 1125 patients with breast cancer who received radiotherapy with radiation fields involving the hear at Beijing Hospital from January 2009 to June 2022. The heart and its substructures of 54 patients were manually delineated, trained an automatic delineation model, and applied this model to the original radiotherapy planning images to automatically extract dosimetric parameters for the heart and substructures in the original plan. Based on the follow-up results, 1125 breast cancer patients were categorized into the CHD event group ( n=19) and non-event group ( n=1106). Wilcoxon rank-sum test, Chi-square test and adjustment for confounding factors using inverse probability weighting were used to compare the mean radiation dose received by the heart and its substructures, age at presentation, history of smoking, history of alcohol consumption, history of hypertension, and history of diabetes between two groups. The influencing factors of CHD were analyzed by univariate and multivariate logistic regression models. Results:The mean heart dose ( P=0.035), mean dose of right atrium ( P=0.049), right coronary artery ( P=0.013), septum ( P=0.045), and right ventricle ( P=0.039) of the event group were higher than that of the non-event group, and the differences were statistically significant. History of alcohol consumption was an independent risk factor for long-term CHD events in the breast cancer patients ( OR=7.35,95% CI: 1.56-25.58, P=0.004). After adjusting for confounding factors using inverse probability weighting, age at presentation was an independent risk factor for long-term CHD events ( OR=1.03, 95% CI: 1.01-1.05, P=0.004). Conclusions:In the breast cancer population with traditional high-risk factors of CHD receiving radiotherapy, the possibility of CHD probably remains high even if the dose of radiation field involving the heart and its substructures is low. Compared to traditional risk factors of CHD, the mean dose to the heart and its substructures in the radiation field of breast cancer patients exerts less impact on the occurrence of CHD after radiotherapy.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.