Accurate prediction of drug-target interactions (DTIs) plays a pivotal role in drug discovery, facilitating optimization of lead compounds, drug repurposing and elucidation of drug side effects. However, traditional DTI prediction methods are often limited by incomplete biological data and insufficient representation of protein features. In this study, we proposed KG-CNNDTI, a novel knowledge graph-enhanced framework for DTI prediction, which integrates heterogeneous biological information to improve model generalizability and predictive performance. The proposed model utilized protein embeddings derived from a biomedical knowledge graph via the Node2Vec algorithm, which were further enriched with contextualized sequence representations obtained from ProteinBERT. For compound representation, multiple molecular fingerprint schemes alongside the Uni-Mol pre-trained model were evaluated. The fused representations served as inputs to both classical machine learning models and a convolutional neural network-based predictor. Experimental evaluations across benchmark datasets demonstrated that KG-CNNDTI achieved superior performance compared to state-of-the-art methods, particularly in terms of Precision, Recall, F1-Score and area under the precision-recall curve (AUPR). Ablation analysis highlighted the substantial contribution of knowledge graph-derived features. Moreover, KG-CNNDTI was employed for virtual screening of natural products against Alzheimer's disease, resulting in 40 candidate compounds. 5 were supported by literature evidence, among which 3 were further validated in vitro assays.
Alzheimer Disease/drug therapy* ; Biological Products/therapeutic use* ; Humans ; Neural Networks, Computer ; Machine Learning ; Drug Discovery/methods* ; Algorithms ; Drug Evaluation, Preclinical/methods*

Objective:To compare and discuss the mid-to-long-term outcomes of mitral valve repair (MVP) versus biological mitral valve replacement (bMVR) in patients aged 60 years and above with rheumatic mitral valve disease.Methods:This is a retrospective cohort study. A total of 765 patients aged 60 years and older, diagnosed with rheumatic mitral valve disease and who underwent MVP or bMVR at Beijing Anzhen Hospital from January 2010 to January 2023, were retrospectively included. Among them, 186 were male and 579 were female, with an age of (66.1±4.5) years (range: 60 to 82 years). Patients were divided into two groups based on the surgical method: the mitral valve repair group (MVP group, n=256) and the bioprosthetic mitral valve replacement group (bMVR group, n=509). A 1∶1 propensity score matching was performed using a caliper value of 0.2 based on preoperative data. Paired sample t-tests, χ2 tests, or Fisher′s exact tests were used for intergroup comparisons. Kaplan-Meier method was employed to plot survival curves and valve-related reoperation rate curves for both groups before and after matching, and Log-rank tests were used to compare the mid-to long-term survival rates and valve-related reoperation rates between the two groups. Results:A total of 765 patients who completed follow-up were ultimately included, with a follow-up period ( M(IQR)) of 5.1(5.0) years (range: 1.0 to 12.9 years). After matching, each group consisted of 256 patients. The incidence of early postoperative atrial fibrillation (39.1% vs. 49.2%, χ2=4.95, P=0.026) and early mortality rates (2.0% vs. 6.2%, χ2=4.97, P=0.026) were lower in the MVP group. Unadjusted Kaplan-Meier analysis showed significantly higher 5-year and 10-year survival rates for the MVP group (92.54% vs. 83.02%, 86.22% vs. 70.19%, Log-rank: P=0.001). After adjustment with propensity scores, the Kaplan-Meier analysis still indicated higher 5-year and 10-year survival rates in the MVP group compared to the bMVR group (92.54% vs. 85.89%, 86.22% vs. 74.83%, Log-rank: P=0.024). There were no significant differences in the rates of valve-related reoperation between the two groups before and after matching (5-year and 10-year reoperation rates pre-matching: 1.75% vs. 0.57%, 5.39% vs. 7.54%, Log-rank: P=0.207; post-matching: 1.75% vs. 0, 5.39% vs. 9.27%, Log-rank: P=0.157). Conclusion:For patients aged 60 years and above with rheumatic mitral valve disease, mitral valve repair offers better mid-to-long-term survival compared to biological valve replacement.

Objective:To compare and discuss the mid-to-long-term outcomes of mitral valve repair (MVP) versus biological mitral valve replacement (bMVR) in patients aged 60 years and above with rheumatic mitral valve disease.Methods:This is a retrospective cohort study. A total of 765 patients aged 60 years and older, diagnosed with rheumatic mitral valve disease and who underwent MVP or bMVR at Beijing Anzhen Hospital from January 2010 to January 2023, were retrospectively included. Among them, 186 were male and 579 were female, with an age of (66.1±4.5) years (range: 60 to 82 years). Patients were divided into two groups based on the surgical method: the mitral valve repair group (MVP group, n=256) and the bioprosthetic mitral valve replacement group (bMVR group, n=509). A 1∶1 propensity score matching was performed using a caliper value of 0.2 based on preoperative data. Paired sample t-tests, χ2 tests, or Fisher′s exact tests were used for intergroup comparisons. Kaplan-Meier method was employed to plot survival curves and valve-related reoperation rate curves for both groups before and after matching, and Log-rank tests were used to compare the mid-to long-term survival rates and valve-related reoperation rates between the two groups. Results:A total of 765 patients who completed follow-up were ultimately included, with a follow-up period ( M(IQR)) of 5.1(5.0) years (range: 1.0 to 12.9 years). After matching, each group consisted of 256 patients. The incidence of early postoperative atrial fibrillation (39.1% vs. 49.2%, χ2=4.95, P=0.026) and early mortality rates (2.0% vs. 6.2%, χ2=4.97, P=0.026) were lower in the MVP group. Unadjusted Kaplan-Meier analysis showed significantly higher 5-year and 10-year survival rates for the MVP group (92.54% vs. 83.02%, 86.22% vs. 70.19%, Log-rank: P=0.001). After adjustment with propensity scores, the Kaplan-Meier analysis still indicated higher 5-year and 10-year survival rates in the MVP group compared to the bMVR group (92.54% vs. 85.89%, 86.22% vs. 74.83%, Log-rank: P=0.024). There were no significant differences in the rates of valve-related reoperation between the two groups before and after matching (5-year and 10-year reoperation rates pre-matching: 1.75% vs. 0.57%, 5.39% vs. 7.54%, Log-rank: P=0.207; post-matching: 1.75% vs. 0, 5.39% vs. 9.27%, Log-rank: P=0.157). Conclusion:For patients aged 60 years and above with rheumatic mitral valve disease, mitral valve repair offers better mid-to-long-term survival compared to biological valve replacement.

Objective:To evaluate and analyze the health status of the elderly from physical health, mental health and social health, so as to understand the health status and health service needs of rural elderly.Methods:A total of 263 elderly people aged 60 years and over(mean aged 70.9±7.9 years, 113 males and 150 females, 125 aged 60-69 years, 98 aged 70-79 years and 40 aged 80 years and over)in Nanwangkong Village, Shaozhuang Town, Qingzhou City, Weifang City, Shandong Province were selected by cluster sampling method.The physical, mental, social and overall health status of the elderly were comprehensively evaluated and analyzed by self-designed questionnaire.Results:The overall health rate was 30%(79 cases), and the physical health, mental health and social health rates were 73.8%(194 cases), 84.0%(221 cases)and 34.6%(91 cases), respectively, in rural elderly in this area.The physical health was better in males than in females in 80~ years old groups( χ2=5.736, P<0.05). The overall health was better in males than in females in the total age group and the 60~69 years old groups( χ2=7.468 and 11.116, both P<0.01). The proportions of unhealthy, basic healthy and healthy people in the overall and the dimensions of physical health, mental health and social health had significant differences in the 60~69, 70~79 and 80~ years old groups( χ2=40.590, 29.342, 18.503 and 27.615, all P<0.01), and the Chi-square test for trend showed that there was a statistically significant downward trend of overall health grade distribution with age( χ2=21.994, 12.831, 16.570 and 22.595, both P<0.01). Conclusions:In this study, 30.0% of the rural elderly were considered healthy, 48.3% were basically healthy, and 21.7% were unhealthy.The health status of the elderly gradually deteriorates with age.The government should strengthen the multidimensional health assessment of the rural elderly and provide the comprehensive health guidance services and targeted interventions for the elderly in terms of disease control, psychological counseling and social participation.

Objective:To develop a set of indexes for the assessment of healthy older adults in China, in order to provide a reference and basis for developing aging-related national policies, standardizing and guiding health management services for the elderly.Methods:A set of indexes for the assessment of healthy older adults in China was established based on a literature review, expert discussions, 2 rounds of Delphi surveys, expert consultations and a cross-sectional study assessing the indexes.Results:The positive coefficients for 2 rounds of expert consultations were 86.25%(69/80)and 94.52%(69/73), respectively.All surveyed experts(100%)specialized in the area of geriatric health and came from 22 provincial-level administrative regions in China.In the two rounds of consultations, the familiarity degree coefficients were 0.706-0.915 and 0.835-0.922, and the authority coefficients were 0.762-0.921 and 0.863-0.932, respectively.The mean importance scores of each index were 6.10-9.74 scores and 7.87-9.56 scores, with perfect score rates of 43%-99% and 75%-99%, respectively.The mean coefficients of variation(CV)were 0.19±0.05(0.07-0.34)and 0.16±0.03(0.10-0.21), respectively.The set of indexes for the assessment of healthy older Chinese adults covered multi-dimensions including physical health, mental health and social health, with 3 primary indexes, 11 secondary indexes and 17 tertiary indexes.Conclusions:The construction process of the set of indexes for the assessment of healthy Chinese adults was scientific and rigorous, and the panelists had a high level of agreement, strong authority and active participation.The set of indexes has comprehensive coverage and an inclusive framework, and indexes at each level are scientific and feasible.It can serve as a reference for the comprehensive assessment of health status of the elderly and for aging-related government policy formulation in the future.

Objective:To evaluate and analyze elderly health on the physical, psychological and social dimensions, so as to understand the health status and care needs of community-dwelling elderly residents.Methods:A cross-sectional study was carried out in the Meiyuan community, Malianwa Street, Haidian District of Beijing during July 22 to August 26, 2021.A total of 404 people aged 60 and above(70.6±8.6 years old)including 169 men and 235 women were enrolled through cluster sampling.All information about community-dwelling elderly residents was collected with face-to-face interviews and a standardized structured questionnaire for the evaluation and analysis of their physical, mental, social and overall health.Results:The rate of overall healthy residents was 21.3%(86), and the rates of physically, mentally and socially healthy residents were 66.8%(270), 86.6%(350) and 24.3%(98), respectively, in this community.There was a sex difference in social health in the whole group( χ2=9.008, P=0.011)and a higher proportion of men than women were considered generally healthy( χ2=8.963, P=0.003). People in the three age groups(224 in the 60-69 group, 109 in the 70-79 group and 71 in the ≥80 group)showed statistically significant differences in overall, physical, mental and social health( χ2=18.473, 61.186, 43.026 and 18.310, P<0.001), which declined with increasing age( χ2=13.172, 23.515, 26.806 and 10.068, P<0.001 or 0.01). Conclusions:s The overall healthy rate is not high among community-dwelling elderly residents in Beijing.The health status of the elderly gradually deteriorates with age.Health assessment for the elderly should be emphasized and targeted health education and prevention should be provided to promote disease prevention and mental health.

Objective:To analyze the process of Chinese expert consensus on the core information on prevention of sarcopenia in the elderly(2021)in China, so as to realize the early diagnosis and treatment of sarcopenia and to improve the quality of life in the elderly.Methods:The index system framework was established by literature review and expert questionnaire discussion, and Delphi expert consultation method was adopted to construct the index system.Results:A total of 109 experts(128 person-times)in Geriatrics from various fields participated in Delphi expert consultation.Positive coefficient for four rounds of expert consultation were 88.9%, 100.0%, 100.0% and 100.0% respectively, with expert authority factors being concentrated on 0.78~0.90.Through 4 rounds of Delphi expert surveys, the core information index system for sarcopenia prevention in the elderly has been definitive: Chinese Expert Consensus(2021)consists of nine indicators including "enhancing public scientific awareness of myosis, and so on."Conclusions:The core information index system for sarcopenia prevention in the elderly has high levels of overall convergence, comprehensive coverage, strong authority, stability, comprehensiveness and popularity.

To summarize the clinical characteristics and chest CT findings of coronavirus disease 2019(COVID-19)patients in Peking Union Medical College Hospital(PUMCH). A total of 13 patients with COVID-19 confirmed at PUMCH from January 20 to February 6,2020 were selected as the research subjects.Their epidemiological histories,clinical characteristics,laboratory tests,and chest CT findings were analyzed retrospectively.The location,distribution,density,and other accompanying signs of abnormal lung CT lesions were recorded,and the clinical types of these patients were assessed. The clinical type was "common type" in all these 13 patients aged(46.8±14.7)years(range:27-68 years).Ten patients had a travel history to Wuhan or direct contact with patients from Wuhan,2 cases had recent travel histories,and 1 case had a travel history to Beijing suburb.The white blood cell(WBC)count was normal or decreased in 92.3% of the patients and the lymphocyte count decreased in 15.4% of the patients.Twelve patients(92.3%)had a fever,among whom 11 patients were admitted due to fever and 2 patients(15.4%)had low fever.Eight patients(61.5%)had dry cough.The CT findings in these 13 patients were all abnormal.The lesions were mainly distributed along the bronchi and under the pleura.The lesions were relatively limited in 8 patients(affecting 1-3 lobes,predominantly in the right or left lower lobe),and diffuse multiple lesions of bilateral lungs were seen in 5 patients.The CT findings mainly included ground glass opacities(GGOs)(=10,76.9%),focal consolidation within GGOs(=7,53.8%),thickened vascular bundle passing through the lesions(=10,76.9%),bronchial wall thickening(=12,92.3%),air bronchogram(=10,76.9%),vacuole signs in the lesions(=7,53.8%),fine reticulation and interlobular septal thickening(=3,23.1%),reversed halo-sign(=2,15.4%),crazy-paving pattern(=2,15.4%),and pleural effusion(=2,15.4%). Most of our patients diagnosed with COVID-19 at PUMCH had a travel history to Wuhan or direct contact with patients from Wuhan.The first symptoms of COVID-19 mainly include fever and dry cough,along with normal or reduced counts of WBC and lymphocytes.CT may reveal that the lesions distribute along the bronchi and under the pleura;they are typically localized GGOs in the early stage but can become multiple GGOs and infiltrative consolidation in both lungs in the advanced stage.Scattered vacuole signs may be visible inside the lesions in some patients.
Adult ; Aged ; Betacoronavirus ; Coronavirus Infections ; diagnostic imaging ; Humans ; Lung ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnostic imaging ; Retrospective Studies ; Tomography, X-Ray Computed

Objective:To investigate the role of multimodal neuronavigation intraoperative and sodium fluorescein-guided techniques in microsurgery for intracranial malignant neoplasm.Methods:A retrospective analysis was conducted on 50 patients with intracranial malignant tumors treated by microsurgery from 2016 to 2019 in Inner Mongolia People′s Hospital. Preoperative imaging included computed tomography (CT), computed tomographic angiography (CTA), magnetic resonance imaging (MRI), MRI: MRA, MRV, DWI, PWI, DTI, DTI, MRS sequence scan, and before the operation, they were fused with the functional nervous system navigation workstation of Bo Yilai to make the navigation plan. During the operation, the functional navigation was combined with low dose fluorescein sodium (2 mg/kg) for operation. Intraoperative neuronavigation was used to determine the location of the tumor and its spatial relationship with the pyramidal tract of the main fiber conduction tract and the large blood vessels, and intraoperative yellow fluorescence mode of pentero900 Zeiss microscope showed the boundary between the tumor and normal brain tissue for tumor resection.Results:There were 38 cases of glioma, 10 cases of brain metastasis of lung cancer, 1 case of brain metastasis of renal clear cell carcinoma and 1 case of spindle cell tumor. The accuracy of preoperative neuronavigation was 95%. Compared with the preoperative lesions, MRI of the head was reexamined 3 days after operation to judge the degree of tumor resection. In this group, 38 cases (76%) were totally resected and 12 cases (24%) were subtotal resected. The 6-month survival rate was 85.9%, the 12-month survival rate was 53.1%, the 18-month survival rate was 24.5%, and the survival time was (15.0 ± 3.2) months.Conclusion:Multimodal functional neuronavigation combined with fluorescein sodium staining can locate and label tumors in real time, improve tumor resection rate, and improve the prognosis of brain cancer patients.

Objective To investigate the effect of CC chemokine receptor 4(CCR4) on sorafenib radiosensitivity and tumorigenesis of hepatocellular carcinoma cells in nude mouse models.Methods Western blot was used to detect the expression of CCR4 in hepatocellular carcinoma cell line.Lentivirus was utilized to construct PLC/PRF/5 and SMMC-7721 cell lines stably overexpressing and silencing CCR4,which were verified by Western blot.The influence of CCR4 on the radiosensitivity of hepatocellular carcinoma cells was assessed by plate clone formation assay.The effect of CCR4 on the tumorigenesis in hepatocellular carcinoma cells in vivo was evaluated by tumorigenesis assay in nude mice.Results CCR4 was highly expressed in highly-metastatic hepatocellular carcinoma cells and lowly expressed in hepatocellular carcinoma cells with low metastases.The PLC/PRF/5 and SMMC-7721 cells,which stably overexpressed and silenced CCR4,were successfully established.Overexpression of CCR4 reversed the inhibitory effect of sorafenib radiotherapy on PLC/PEF/5,whereas knockdown of CCR4 could increase the radiosensitivity of SMMC-7721 to sorafenib.Overexpressing CCR4 could promote the tumorigenicity of PLC/PEF/5,whereas knockdown of CCR4 could inhibit the tumorigenicity of SMMC-7721 in nude mice.Conclusion CCR4 overexpression significantly reduces the radiosensitivity of PLC/PRF/5 and increases the tumorigenicity in nude mice,whereas knockdown of CCR4 considerably increases the chemosensitivity and radiosensitivity of SMMC-7721 and suppresses the tumorigenicity in nude mice.