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

Biotechnological pharmaceutics is an important course for pharmacy undergraduates , however there are many problems in current curriculum design and teaching methods. With the advantage of our platform National Engineering Research Center of Immunological Products, we tried to carry out the teaching reformation based on Excellent Engineer Education and Training Plan. We optimized the curriculum standards and teaching design, highlighted the combination ofBiotechnological pharmaceuticsand Engineering, strengthened the experiment teaching, tried the reformation of teaching method such as flipped classroom and PBL, strengthened the cultivation of innovative thinking and scientific research ability. Our teaching reformation is beneficial to cultivating the compound talents in the field of biotechnological pharmaceutics.

Objective To investigate the characteristics of IL-22 in Helicobacter pylori (H.pylori)infection.Methods Thirty H.pyloripositive and fifteen H.pylori negative gastric biopsy specimens were enrolled,IL-22 mRNA expression was detected by real-time PCR and the protein level of IL-22 was determined by ELISA in gastric tissue.The H.pyloriand cell coculture system was established and IL-22 expression was measured by real-time PCR to investigate the main source of IL-22 in gastric tissue.The IL-22-producing T cell was examined by FCM in the gastric mucosa tissue.Results Gastric mucosal IL-22 mRNA and protein levels were significantly higher in H.pylori-positive patients than uninfected patients (P＜0.05).A H.pyloriand cell coculture system was established successfully and gastric epithelial cell and T cell were the main source of IL-22 in gastric tissue.IL-22 was produced by CD4+ and CD8+ T cells and these T cells were increased in H.pylori-infected gastric mucosa (P＜0.05).Conclusion IL-22 took part in H.pyloriinfection induced immune response and increased IL-22-producing T cells was the important feature of H.pyloriinfection.

This paper analyzed innovative education management system,innovative education resources,innovative education mode and innovative education evaluation standard through practicing‘integration of production,study and research’ teaching platform. Meanwhile,this paper explored the optimization system of innovative education in medical undergraduate teaching.

Objective To prepare high-titer monoclonal antibodies against STX2A1 subunit of enterohemorrhagic E.coli(EHEC) O157∶H7.Methods BALB/c mice were immunized with GST-STX2A1 fusion protein and the spleen cells of BALB/c mice which were not immunized were used as feeder cells.Hybridoma technique,natural STX2A protein and ELISA test were used to prepare and screen the hybridoma cell lines of monoclonal antibodies against STX2A1.The ascites developed by injecting the hybridoma cells into abdominal cavity of the BALB/c mice and was purified with Protein A-Sepharose.The subclasses and isotypes were identified by mouse monoclonal antibody isotyping kit.The antigenic epitopes that can be recognized by STX2-1A3,STX2-1E10 and STX2-3A7 were analyzed by the ELISA additivity test.Results Three hybridoma cell strains were obtained and named as STX2-1A3,STX2-1E10 and STX2-3A7,respectively,all of which produced monoclonal antibodies specifically against STX2A1.The isotypes of the monoclonal antibodies were IgG1?,IgG1?,and IgG3? and the affinity constant was 5.76 ?109,1.21 ?109 and 3.97 ?108,respectively.Conclusion We have successfully prepared three hybridoma cell strains which secrete high-titer and highly specific monoclonal antibodies against STX2A1.Our study provides a basis for researching the early diagnosis,prevention and cure of the disease induced by EHEC O157∶H7.

Objective　To recombine and express a component of urease B subunit transmembrane protein of helicobacter pylori. Methods　A 732 bp gene fragment of urease B subunit of helicobacter pylori was cloned into pET11C and transformed into BL21（DE3）E.coli. The positive clone was induced with IPTG. The expression of target protein was analysed by SDS-PAGE and Western blot. Results　It is successful to construct the recombinant plasmid pET-UreB0.7 containing urease B subunit 0.7 kb gene fragment. A protein （MW≈28 000 u） with immunoreactivity， was expressed by 19.8％ in BL21（DE3）E.coli induced with IPTG. Conclusions　The recombinant component of urease B subunit transmembrane protein may play a role in the research of its biological function and might be used as the vaccine against helicobacter pylori.

Objective To explore the method of endovascular therapy for complicated aortic dissections.(Methods) The clinical data of 25 patients with complicated aortic dissections were analysed retrospectively.Results The patients′ ages ranged from 31-72 years with a mean of 50.2 years.Among the 25 cases,6 cases had severe ischemia of mesenteric artery,5 cases had renal artery ischemia,4 cases had severe(ischemia) of both legs,3 cases had renal arteries ischemia combined with superior mesenteric artery ischemia,2 had complicated aortic dissection combined with AAA,and in 5 cases the true aortic lumen was totally(compressed) by the false aneurysmal lumen.All patients underwent endovascular therapy,and the instant(technique) was successfully performed in all patients.Endoleak occurred in 3 cases after the stent-graft(deployment),it stopped spontaneously in 2 of them 7 days later,and 1 case with endoleak waiting for(treatment).In the other 22 patients,angiography after the operation showed that all the diseased area were sealed completely,and the viscera arterial blood supply was restored mainly via the true lumen.All the(patients) were cured and discharged.Conclusions In the management of complicated aortic dissections,(endoluminal) technique is simple,less traumatic,safe and has less complications as compared to the traditional operation.Improvement of the endoluminal technique is essential for successful treatment of these complicated cases.

Objective To study the character of transformation of H.pylori into coccoid form under oxidative stress, and the changes in the biological charasteristics after transformation. Methods The coccoid form of H.pylori was studied with bacteriological, enymological, and genetical methods to identify its differences from the original form. Animal experiment was conducted to determine its implantation capacity. Results Morphological transformation from spiral to coccoid form occurred with the prolongation of culture under oxygen stress. The metabolic activity was reduced gradually, finally maintained at a lower level. The activities of urease, alkaline phosphatase and acid phosphatase were decreased markedly. The mRNA levels of main virulence factors were declined. Both mRNA and activities of enzyme of Sod B and Kat retained high levels. A part of the coccoid forms showed reversion to helical form, and colonization in mice stomach could be found after being inoculated to mice. Conclusions The metabolism and virulence of H.pylori were all lowered under oxidative stress, but a part of the coccoid form may be viable. Sod B and Kat may play an important role in the oxygen metabolism of H.pylori.