OBJECTIVES: To develop a heterogeneous graph prediction method based on the fusion of multi-layer semantics and topological information for addressing the challenges in drug-target interaction prediction, including insufficient modeling of high-order semantic dependencies, lack of adaptive fusion of semantic paths, and over-smoothing of node features. METHODS: A heterogeneous graph network with multiple types of entities such as drugs, proteins, side effects, and diseases was constructed, and graph embedding techniques were used to obtain low-dimensional feature representations. An adaptive metapath search module was introduced to automatically discover semantic path combinations for guiding the propagation of high-order semantic information. A semantic aggregation mechanism integrating multi-head attention was designed to automatically learn the importance of each semantic path based on contextual information and achieve differentiated aggregation and dynamic fusion among paths. A structure-aware gated graph convolutional module was then incorporated to regulate the feature propagation intensity for suppressing redundant information and redcuing over-smoothing. Finally, the potential interactions between drugs and targets were predicted through an inner product operation. RESULTS: Compared with existing drug-target interaction prediction methods, the proposed method achieved an average improvement of 3.4% and 2.4%, 3.0% and 3.8% in terms of the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUPRC) on public datasets, respectively. CONCLUSIONS The drug-target interaction prediction method developed in this study can effectively extract complex high-order semantic and topological information from heterogeneous biological networks, thereby improving the accuracy and stability of drug-target interaction prediction. This method provides technical support and theoretical foundation for precise drug target discovery and targeted treatment of complex diseases.
Semantics ; Humans ; Drug Interactions ; Neural Networks, Computer ; Algorithms

Objective To evaluate the long-term efficacy of transjugular intrahepatic portosystemic shunt(TIPS)with bare stents and Fluency covered stents in the treatment of portal hypertension,and to discuss its clinical value.Methods The clinical data of 29 patients with intractable ascites or esophagogastric fundus varices rupture and hemorrhage caused by cirrhotic portal hypertension,who received TIPS with bare stents and covered stents at the First Affiliated Hospital of Xinjiang Medical University of China(25 patients)and the Lishui Municipal Central Hospital of China(4 patients)between August 2012 and December 2017,were retrospectively analyzed.The patients were regularly followed up to check the survival status.The postoperative cumulative shunt patency rate and cumulative survival rate of the patients were analyzed by Kaplan-Meier method.Results The technical success rate of TIPS was 100％.The mean portal vein pressure was decreased from preoperative(40.21±3.24)cmH2O to postoperative(24.55±3.55)cmH2O(P＜0.05).The patients were followed up for 5.1-10.5 years.The postoperative 1-,3-,5-,7-year primary cumulative patency rates of the shunt were 89.7％,75.9％,75.9％ and 52.5％,respectively.The postoperative 5-,7-,9-and 10-year cumulative survival rates were 100％,66.9％,66.9％ and 33.4％,respectively.The incidence of hepatic encephalopathy was 13.8％(4/29).Conclusion Using bare stents combined with Fluency covered stents for TIPS is clinically safe and effective in the treatment of portal hypertension.This technique carries higher long-term shunt patency rate and low incidence of hepatic encephalopathy.Therefore,it can be used as a substitute for Viatorr stent when necessary.(J Intervent Radiol,2024,33:295-299)

Objective To evaluate the clinical application value of medical tissue glue in the treatment of acute hemoptysis by bronchial arterial embolization(BAE).Methods The clinical data of 78 patients who underwent emergency BAE for hemoptysis were retrospectively collected.Among them,18 patients who underwent embolization with medical tissue glue were selected as a study group,and other 18 patients who underwent embolization with absorbent gelatin sponge particles and spring coil were selected as a control group.The technical success rates,average surgical operation time,average surgical cost,postoperative hemoptysis recur-rence rate,and incidence of adverse reactions of the two groups were compared and analyzed.Results The technical success rates of the two groups were both 100％.There were no statistically significant differences in recurrence rate of postoperative hemoptysis and incidence of adverse reactions between the two groups(P＞0.05).The average surgical operation time of study group and control group were 53.4 min[(53.4±2.2)min]and 65.4 min[(65.4±2.8)min],and the average surgical cost were 3 651 yuan[(3 651±102.7)yuan]and 5 094 yuan[(5 094±136.3)yuan],respectively.Compared with the control group,the average surgical operation time and aver-age surgical cost of the study group were shorter,and the differences were statistically significant(P＜0.05).Conclusion Compared with absorbent gelatin sponge particles combined with spring coil embolization,the use of medical tissue glue for embolization is also safe and effective in the treatment of acute hemoptysis patients by BAE.The average surgical operation time is shorter,and the surgical cost for patients is lower.It is worth promoting in clinical practice.

Objective:Evaluation of ultrasound-guided radiofrequency of hyperthermia combined with recombinant human adenovirus H101 for the treatment of hepatocellular carcinoma (HCC).Methods:In vitro cell therapy experiments, luciferase/red fluorescent protein/lentivirus mediated McA-RH7777 cells were conducted and divided into 4 groups. Each group was repeatedly treated for 6 times: (1) recombinant human adenovirus type 5 H101 [(multiplicity of infection, MOI)=0.2]+ RFH group, heated at 42℃ for 30 min; (2) recombinant human adenovirus type 5 H101 alone (MOI=0.2); (3) RFH alone, heated at 42℃ for 30 min; (4) control group: physiological saline group. Twenty-four nude rats weighing 180-220 g were selected to establish a nude rat model of orthotopic HCC. They were divided into 4 groups with 6 rats in each group: (1) H101+ RFH combined treatment group: RFH electrode needles were punctured to the center of the tumor in the liver of nude rats under ultrasound guidance, and H101 was directly injected through the electrode injection end. RFH was delivered to the tumor at a temperature of 42℃ for 30 min; (2) H101 treatment group: MOI=0.2; (3) RFH treatment group; (4) sham surgery group. Fluorescence microscopy imaging was used to evaluate the viability of cells in vitro experiments. For in vivo validation, ultrasound imaging was used to follow up the tumor size. Tumor gross specimens and pathological changes were also evaluated.Results:Twenty-four hours after treatment, the survival rate of cells in the H101+ RFH group was the lowest under fluorescence microscopy. The results of MTS quantitative analysis showed that the relative absorbance of mezzanine in the H101+ RFH group cells was lower than that in the H101 group alone [(25.00±2.27)% vs. (69.50±4.53)%], the RFH group alone [(25.00±2.27)% vs. (92.83±1.66)%], and the control group [(25.00±2.27)% vs. 100%], with statistical significance (all P<0.001). The number of apoptotic cells in the H101+ RFH group was higher than that in the H101 group alone [(54.5±3.1)% vs. (25.2±1.4)%], the RFH group alone [(54.5±3.1)% vs. (5.7±0.6)%], and the control group [(54.5±3.1)% vs. (3.9±0.5)%], all of which showed statistically significant differences (all P<0.001). The relative tumor volume of nude rats in the H101+ RFH combination treatment group was smaller than that in the H101 treatment group (0.776±0.127 vs. 1.312±0.188), RFH treatment group (0.776±0.127 vs. 1.893±0.571), and sham surgery group (0.776±0.127 vs. 1.977±0.590), all of which had statistical significance (all P<0.001). The number of apoptotic cells in nude rats in the H101+ RFH combination treatment group was higher than that in the H101 treatment group [(49.85±4.00%)% vs. (22.70±0.65)%], the RFH treatment group [(49.85±4.00% vs. (5.36±0.84)%], and the sham surgery group [(49.85±4.00)% vs. (5.96±0.78)%], all of which showed statistically significant differences (all P<0.001). Conclusion:Ultrasound guided RFH combined with recombinant human adenovirus H101 has a promoting effect on the treatment of HCC.

Cardiovascular System ; Heart

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Objective:To assess the safety and effectiveness of amphotericin B cholesteryl sulfate complex for injection in the context of empirical and diagnostic antifungal therapy for patients with hematological malignancies in addition to invasive fungal illness.Methods:This single-arm clinical study enrolled 30 patients who received empirical and diagnostic-driven antifungal therapy for hematological malignancies combined with invasive fungal disease. The primary endpoint was safety. Response rate, fever duration, and treatment completion rate were all considered secondary objectives.Results:30 participants were eventually enrolled in the study, and the treatment completion rate was 80.0% . Most adverse events were in grades 1-2. Infusion response was the most frequent adverse event (24/30, 80% ) . The overall response rate was 80.0% (24/30) . In 24 patients (80.0% ) , the fever persisted for 1 day.Conclusions:Treatment of invasive fungal illness in conjunction with hematological malignancies showed good efficacy and safety with amphotericin B cholesteryl sulfate complex for injection.

Consensus ; Critical Illness ; Humans ; Serum Albumin ; Serum Albumin, Human

Objective:To investigate the clinical pathological and epidemiological characteristics of primary esophageal malignant melanoma (PMME).Methods:The clinical pathology data of 180 PMME patients in the esophageal cancer database of the key laboratory of esophageal cancer research in Henan Province from 1973 to 2016 were collected, of which 136 were male, aged (58.5±9.0) years, 44 were female, aged (56.7±12.2) years. Kaplan-Meier and Log rank test were used for survival analysis, Cox regression scale model was used for risk factor analysis.Results:The incidence of PMME is 0.036% (180/500, 000), mostly were male (about 3∶1 for men: female). The common sites of PMME were the lower part of the esophagus (48.9%, 85/174), followed by the middle section of the esophagus (46.0%, 80/174) and the upper part of the esophagus (5.2%, 9/174). No black particles were seen in the PMME cells of 3 patients under microscope, and strong positive expressions of Melan-A and HMB453 were observed in these 3 patients by immunohistochemical results. Of the 129 patients who had a routine preoperative esophageal biopsy, 69 were undiagnosed with PMME (53.5%). The medium survival time of the whole group was 7.9 months, and the survival rates of 1, 2, 3, 5 years were 25.0%, 7.9%, 6.6% and 1.3%, respectively. The univariate analysis showed that N, M, TNM phase and radiotherapy were related to the overall survival of patients ( P<0.05). Multivariate analysis showed that TNM phase and radiotherapy were the independent risk factors for overall survival of patients ( P<0.05). Conclusions:PMME is more common in men, the common site of the disease is the lower part of the esophagus. The preoperatively missed diagnosis rate of Chinese PMME is high. TNM phase and radiotherapy are the independent risk factors for overall survival of patients.

Objective:To investigate the clinical pathological and epidemiological characteristics of primary esophageal malignant melanoma (PMME).Methods:The clinical pathology data of 180 PMME patients in the esophageal cancer database of the key laboratory of esophageal cancer research in Henan Province from 1973 to 2016 were collected, of which 136 were male, aged (58.5±9.0) years, 44 were female, aged (56.7±12.2) years. Kaplan-Meier and Log rank test were used for survival analysis, Cox regression scale model was used for risk factor analysis.Results:The incidence of PMME is 0.036% (180/500, 000), mostly were male (about 3∶1 for men: female). The common sites of PMME were the lower part of the esophagus (48.9%, 85/174), followed by the middle section of the esophagus (46.0%, 80/174) and the upper part of the esophagus (5.2%, 9/174). No black particles were seen in the PMME cells of 3 patients under microscope, and strong positive expressions of Melan-A and HMB453 were observed in these 3 patients by immunohistochemical results. Of the 129 patients who had a routine preoperative esophageal biopsy, 69 were undiagnosed with PMME (53.5%). The medium survival time of the whole group was 7.9 months, and the survival rates of 1, 2, 3, 5 years were 25.0%, 7.9%, 6.6% and 1.3%, respectively. The univariate analysis showed that N, M, TNM phase and radiotherapy were related to the overall survival of patients ( P<0.05). Multivariate analysis showed that TNM phase and radiotherapy were the independent risk factors for overall survival of patients ( P<0.05). Conclusions:PMME is more common in men, the common site of the disease is the lower part of the esophagus. The preoperatively missed diagnosis rate of Chinese PMME is high. TNM phase and radiotherapy are the independent risk factors for overall survival of patients.