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 develop a predictive model for guiding blood transfusion decisions in pediatric patients with traumatic brain injury(TBI)by identifying and analyzing key factors that influence blood transfusion requirements.Methods A retrospective analysis was conducted on the clinical data of 1,535 pediatric patients with TBI admitted to four medical institutions from January 1,2015,to December 31,2022.Patients were divided into two groups:those who received red blood cell transfusions during hospitalization and those who did not.Comparative analyses were performed on demographic,clinical,and laboratory data between these two groups.Logistic regression analysis was used to identify risk factors associated with in-hospital blood transfusion,and a predictive model was developed using a nomogram.The performance of this model was evaluated using a receiver operating characteristic(ROC)curve.Results Significant differences were observed between the blood transfusion and non-blood transfusion groups in terms of baseline demographics,clinical indicators,and laboratory test results(all P<0.05).Patients in the blood transfusion group exhibited significantly higher in-hospital mortality,compli-cation rates,use of mechanical ventilation,ICU admission rates,and length of stay compared to those in the non-blood transfusion group(all P<0.05).Multivariate logistic regression analysis identified heart rate,presence of other fractures,treatment methods,hemoglobin(Hb),platelet count(Plt),activated partial thromboplastin time(APTT),and D-dimer levels as independent risk factors for blood transfusion in TBI patients.The area under the ROC curve for the blood transfusion prediction model,based on these independent risk factors,was 0.95(95%CI:0.94～0.97),indicating excellent predictive accuracy.Calibration and decision curves further validated the robust-ness and reliability of the model's predictive capacity.Conclusions Heart rate,presence of other fractures,treatment methods,Hb,Plt count,APTT,and D-dimer levels serve as independent risk factors for blood transfusion in TBI patients.The prediction model developed based on these factors demonstrates excellent predictive performance,thereby guiding clinicians in making informed blood transfusion decisions and enhancing the success rate of patient outcomes.

Objective:To compare the clinical efficacy of autologous bone grafting or bioceramic bone grafting combined with locking compression plate (LCP) internal fixation in the treatment of Schatzker type II and III tibial plateau fractures.Methods:A retrospective analysis was conducted on 104 patients with Schatzker type II and III tibial plateau fractures who underwent surgical treatment at the Department of Orthopedics, PLA Central Theater Command General Hospital from January 2010 to December 2021. The cohort comprised 55 males and 49 females, with an average age of 49.13±13.80 years (range 18-73 years). All fractures were unilateral: 55 on the left and 49 on the right. According to the Schatzker classification, 59 were Type II and 45 were Type III. Causes of injury included traffic accidents (48 cases), falls from height (3 cases), sprains or falls (45 cases), and other causes (8 cases). During surgery, bioceramic material or allograft bone tissue was implanted into the collapsed tibial plateau region to restore articular surface flatness. Based on graft type, patients were divided into the allograft bone group (63 cases) and the bioceramic group (41 cases). All cases underwent proximal lateral tibial LCP internal fixation. The two groups were compared in terms of operative time, intraoperative blood loss, bone graft volume, length of hospital stay, fracture healing time, and postoperative complications. The Rasmussen radiographic collapse score was used to evaluate fracture reduction, and the Hospital for Special Surgery (HSS) score system was used to assess knee joint function.Results:All patients were followed up for 12(12, 13) months (range 12-16 months). The fracture healing time in the allograft bone group was 13.70±1.36 weeks (range 11-16 weeks), which was significantly shorter than that in the bioceramic group: 14.59±1.73 weeks (range 11-19 weeks) ( t=2.911, P=0.004). The time to full weight-bearing in the allograft group was 15.0(14.0, 17.0) weeks (range 13-23 weeks), which was shorter than the 16.0 (15.5, 18.5) weeks (range 12-24 weeks) in the bioceramic group, showing a statistically significant difference ( Z=-3.019, P=0.002). At 12 months postoperatively, the Rasmussen radiographic collapse score was 1(0, 1) in the bioceramic group, significantly lower than the 1(1, 2) score in the allograft group ( Z=-2.083, P=0.037). No statistically significant differences were observed between the two groups in bone graft volume, surgical duration, intraoperative blood loss, hospitalization duration, or HSS scores at 6 and 12 months postoperatively ( P>0.05). The complication rate was 6.3% (4/63) in the allograft group and 2.4% (1/41) in the bioceramic group, with no statistically significant difference (χ 2=0.830, P=0.362). Conclusions:For Schatzker type II and III tibial plateau fractures, the use of allograft bone or bioceramic combined with LCP internal fixation can achieve good results. Allograft bone has advantages in terms of fracture healing speed and early weight-bearing recovery, while bioceramic is more effective in maintaining joint surface stability.

Objective:To compare the clinical efficacy of autologous bone grafting or bioceramic bone grafting combined with locking compression plate (LCP) internal fixation in the treatment of Schatzker type II and III tibial plateau fractures.Methods:A retrospective analysis was conducted on 104 patients with Schatzker type II and III tibial plateau fractures who underwent surgical treatment at the Department of Orthopedics, PLA Central Theater Command General Hospital from January 2010 to December 2021. The cohort comprised 55 males and 49 females, with an average age of 49.13±13.80 years (range 18-73 years). All fractures were unilateral: 55 on the left and 49 on the right. According to the Schatzker classification, 59 were Type II and 45 were Type III. Causes of injury included traffic accidents (48 cases), falls from height (3 cases), sprains or falls (45 cases), and other causes (8 cases). During surgery, bioceramic material or allograft bone tissue was implanted into the collapsed tibial plateau region to restore articular surface flatness. Based on graft type, patients were divided into the allograft bone group (63 cases) and the bioceramic group (41 cases). All cases underwent proximal lateral tibial LCP internal fixation. The two groups were compared in terms of operative time, intraoperative blood loss, bone graft volume, length of hospital stay, fracture healing time, and postoperative complications. The Rasmussen radiographic collapse score was used to evaluate fracture reduction, and the Hospital for Special Surgery (HSS) score system was used to assess knee joint function.Results:All patients were followed up for 12(12, 13) months (range 12-16 months). The fracture healing time in the allograft bone group was 13.70±1.36 weeks (range 11-16 weeks), which was significantly shorter than that in the bioceramic group: 14.59±1.73 weeks (range 11-19 weeks) ( t=2.911, P=0.004). The time to full weight-bearing in the allograft group was 15.0(14.0, 17.0) weeks (range 13-23 weeks), which was shorter than the 16.0 (15.5, 18.5) weeks (range 12-24 weeks) in the bioceramic group, showing a statistically significant difference ( Z=-3.019, P=0.002). At 12 months postoperatively, the Rasmussen radiographic collapse score was 1(0, 1) in the bioceramic group, significantly lower than the 1(1, 2) score in the allograft group ( Z=-2.083, P=0.037). No statistically significant differences were observed between the two groups in bone graft volume, surgical duration, intraoperative blood loss, hospitalization duration, or HSS scores at 6 and 12 months postoperatively ( P>0.05). The complication rate was 6.3% (4/63) in the allograft group and 2.4% (1/41) in the bioceramic group, with no statistically significant difference (χ 2=0.830, P=0.362). Conclusions:For Schatzker type II and III tibial plateau fractures, the use of allograft bone or bioceramic combined with LCP internal fixation can achieve good results. Allograft bone has advantages in terms of fracture healing speed and early weight-bearing recovery, while bioceramic is more effective in maintaining joint surface stability.

Objective To develop a predictive model for guiding blood transfusion decisions in pediatric patients with traumatic brain injury(TBI)by identifying and analyzing key factors that influence blood transfusion requirements.Methods A retrospective analysis was conducted on the clinical data of 1,535 pediatric patients with TBI admitted to four medical institutions from January 1,2015,to December 31,2022.Patients were divided into two groups:those who received red blood cell transfusions during hospitalization and those who did not.Comparative analyses were performed on demographic,clinical,and laboratory data between these two groups.Logistic regression analysis was used to identify risk factors associated with in-hospital blood transfusion,and a predictive model was developed using a nomogram.The performance of this model was evaluated using a receiver operating characteristic(ROC)curve.Results Significant differences were observed between the blood transfusion and non-blood transfusion groups in terms of baseline demographics,clinical indicators,and laboratory test results(all P<0.05).Patients in the blood transfusion group exhibited significantly higher in-hospital mortality,compli-cation rates,use of mechanical ventilation,ICU admission rates,and length of stay compared to those in the non-blood transfusion group(all P<0.05).Multivariate logistic regression analysis identified heart rate,presence of other fractures,treatment methods,hemoglobin(Hb),platelet count(Plt),activated partial thromboplastin time(APTT),and D-dimer levels as independent risk factors for blood transfusion in TBI patients.The area under the ROC curve for the blood transfusion prediction model,based on these independent risk factors,was 0.95(95%CI:0.94～0.97),indicating excellent predictive accuracy.Calibration and decision curves further validated the robust-ness and reliability of the model's predictive capacity.Conclusions Heart rate,presence of other fractures,treatment methods,Hb,Plt count,APTT,and D-dimer levels serve as independent risk factors for blood transfusion in TBI patients.The prediction model developed based on these factors demonstrates excellent predictive performance,thereby guiding clinicians in making informed blood transfusion decisions and enhancing the success rate of patient outcomes.

Objective:To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia(TDT),and reveal the changes of metabolic pattern in children with TDT.Methods:23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected,and 11 healthy children who underwent physical examination during the same period were selected as the control group.The routine indexes between children with TDT and the control group were compared,and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry.An OPLS-DA model was established to perform differential analysis on the detected metabolites,and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites.Results:The results of routine testing showed that the indexes of ferritin,bilirubin,total bile acid,glucose and triglycerides in children with TDT were significantly higher than those in healthy controls,while hemoglobin and total cholesterol were significantly lower(all P＜0.05).However there was no significant difference in lactate dehydrogenase between the two groups(P＞0.05).Compared with the control group,190 differential metabolites(VIP＞1)were identified in TDT children.Among them,168 compounds such as arginine,proline and glycocholic acid were significantly increased,while the other 22 compounds such as myristic acid,eleostearic acid,palmitic acid and linoleic acid were significantly decreased.The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism.Conclusion:The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group.This finding is helpful to optimize the treatment choice for children with TDT,and provides a new idea for clinical treatment.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To explore the regulatory role of transient receptor potential channel 6(TRPC6)on podocyte autophagy under the influence of homocysteine(Hcy)in mouse kidney.Methods Mouse renal podocytes were divided into control group and Hcy groups(stimulated by Hcy at 40,60,80 and 100 μmol/L for 48 h).The level of TRPC6 mRNA was assessed using quantitative reverse transcription polymerase chain reaction(qRT-PCR)to identify the optimal Hcy concentration for subsequent experiments.Western blotting was employed to evaluate the expression levels of autophagy-related proteins LC3 Ⅱ and p62,as well as the expression levels of podocyte structural proteins Nephrin and Podocin.The expression levels of TRPC6 mRNA and protein in both groups were determined using qRT-PCR,Western blotting and immunofluorescence.Transfections of cells with TRPC6 overexpression or interference were set as follows:(1)control group(untreated),negative control group of TRPC6 overexpression,and TRPC6 overexpression group;(2)control group(untreated),negative control group of TRPC6 interference,and TRPC6 interference group(si-1,si-2,si-3).The expression level of TRPC6 was detected using qRT-PCR.The cells after overexpressing or interfering of TRPC6 were further set as follows:(1)control group(untreated),Hcy group(80 μmol/L Hcy added),TRPC6 overexpression control+Hcy group,TRPC6 overexpression+Hcy group;(2)control group(untreated),Hcy group,TRPC6 interference control+Hcy group,and TRPC6 interference+Hcy group.The expression levels of p62,LC3 Ⅱ,and TRPC6 proteins were detected using Western blotting.Results qRT-PCR detection results showed that compared with control group,the expression level of TRPC6 mRNA in Hcy group increased with the increase of Hcy concentration,with the highest expression level observed at 80 μmol/L Hcy.Therefore,80 μmol/L Hcy was selected as the optimal concentration for intervention.At this time,the expression level of autophagy-related protein LC3 Ⅱ increased,and the expression level of p62 decreased(P<0.05).Western blotting results showed that compared with control group,the expression levels of podocyte-related proteins Nephrin and Podocin in Hcy group were significantly decreased(P<0.05).qRT-PCR results showed that compared with control group,the expression level of TRPC6 mRNA in Hcy group was significantly increased(P<0.05).Compared with negative control group for TRPC6 overexpression,both mRNA and protein expression levels of TRPC6 in TRPC6 overexpression group were significantly higher(P<0.05).Compared with negative control group for TRPC6 interference,both mRNA and protein expression levels of TRPC6 in TRPC6 interference group were significantly decreased(P<0.05).Western blotting results showed that compared with negative control group for TRPC6 overexpression,the expression level of autophagy-related protein LC3 Ⅱ in TRPC6 overexpression+Hcy group was significantly increased,and the expression level of p62 was significantly decreased(P<0.05).Compared with TRPC6 negative control+Hcy group for TRPC6 interference+Hcy,the expression level of autophagy-related protein LC3 Ⅱ in TRPC6 interference+Hcy group was significantly decreased,and the expression level of p62 was significantly increased(P<0.05).Conclusion Hcy can induce autophagy of renal podocytes.Inhibiting the expression of TRPC6 can significantly reduce the autophagy damage to podocytes.