1.DHGT-DTI: Advancing drug-target interaction prediction through a dual-view heterogeneous network with GraphSAGE and Graph Transformer.
Mengdi WANG ; Xiujuan LEI ; Ling GUO ; Ming CHEN ; Yi PAN
Journal of Pharmaceutical Analysis 2025;15(10):101336-101336
Computational approaches for predicting drug-target interactions (DTIs) are pivotal in advancing drug discovery. Current methodologies leveraging heterogeneous networks often fall short in fully integrating both local and global network information. To comprehensively consider network information, we propose DHGT-DTI, a novel deep learning-based approach for DTI prediction. Specifically, we capture the local and global structural information of the network from both neighborhood and meta-path perspectives. In the neighborhood perspective, we employ a heterogeneous graph neural network (HGNN), which extends Graph Sample and Aggregate (GraphSAGE) to handle diverse node and edge types, effectively learning local network structures. In the meta-path perspective, we introduce a Graph Transformer with residual connections to model higher-order relationships defined by meta-paths, such as "drug-disease-drug", and use an attention mechanism to fuse information across multiple meta-paths. The learned features from these dual perspectives are synergistically integrated for DTI prediction via a matrix decomposition method. Furthermore, DHGT-DTI reconstructs not only the DTI network but also auxiliary networks to bolster prediction accuracy. Comprehensive experiments on two benchmark datasets validate the superiority of DHGT-DTI over existing baseline methods. Additionally, case studies on six drugs used to treat Parkinson's disease not only validate the practical utility of DHGT-DTI but also highlight its broader potential in accelerating drug discovery for other diseases.
2.Exploration on the Mechanism of Yizhu Wendan Decoction in Treating Eczema Based on GEO Database Combined with Network Pharmacology and Experimental Verification
Yijie WANG ; Tingting GUO ; Yongjun LI ; Ziyi LI ; Meng ZHANG ; Mengdi SHI ; Shengnan GU ; Youpeng WANG ; Zhijun LI
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(4):32-41
Objective To explore the mechanism of Yizhu Wendan Decoction in treating eczema through GEO database combined with network pharmacology and experimental verification.Methods TCMSP,BATMAN-TCM and ETCM databases were used to screen the active components of Yizhu Wendan Decoction.Disease target information related to eczema was collected through GEO database.The drug-component-target network and PPI network were constructed by intersections of active component targets and disease targets.GO and KEGG pathway enrichment analyses were performed using DAVID database.CCK-8 method was used to screen out the optimal intervention concentration of freeze-dried powder of Yizhu Wendan Decoction.HaCaT cells were divided into control group,model group,Yizhu Wendan Decoction low concentration group,Yizhu Wendan Decoction high concentration group,si-IL-17RA group,si-IL-17RA+Yizhu Wendan Decoction low concentration group,si-IL-17RA+Yizhu Wendan Decoction high concentration group,Dexamethasone group,si-IL-17RA+Dexamethasone group.Each group was given relevant intervention.The expressions of chemokines and inflammatory factors were detected by qPCR.EdU and Annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis.Western blot was performed to detect the expressions of proteins related to apoptosis,skin barrier and IL-17 signaling pathway.Results By using databases,180 active components of Yizhu Wendan Decoction were obtained.Combined with GEO database microarrays related to eczema(GSE6012 and GSE57225),8 potential targets of Yizhu Wendan Decoction in the treatment of eczema were obtained.KEGG enrichment pathway mainly involved IL-17 signaling pathway,lipid and atherosclerotic,TNF signaling pathway,fluid shear stress and atherosclerotic,etc.When Yizhu Wendan Decoction freeze-dried powder concentration was 100 μg/mL,cell viability was the strongest.Yizhu Wendan Decoction could significantly inhibit the mRNA expressions of chemokines and inflammatory factors CCL17,CCL22,IL-1β,TNF-α,IL-6,IFN-γ,and increase the mRNA expression of IL-4 in eczema.It promoted the proliferation of HaCaT cells,increased the protein expression of Bcl-2,and reduced the protein expressions of Bad and Cleaved Caspase-3,thus inhibiting HaCaT cells apoptosis;promoted the protein expressions of FLG and LOR,and reduced the expression of MMP9,MMP1,CCL2,FOSL1,IL-17RA proteins in IL-17 signaling pathway.Conclusion Yizhu Wendan Decoction can treat eczema with multiple components,multiple pathways and multiple targets,promote the proliferation of HaCaT cells,inhibit their apoptosis,and restore the skin barrier.Its mechanism may be related to inhibiting the activation of IL-17 signaling pathway.
3.Meta synthesis of communication of diseases between cancer patients and minor children
Xiaoyu GUO ; Yingying LI ; Yuli LI ; Mengdi LIU ; Yanqiu GAO ; Zhenmei ZHANG
Chinese Journal of Modern Nursing 2025;31(34):4691-4698
Objective:To conduct evidence synthesis on disease communication between parents and their minor children from the perspective of parents with cancer, so as to provide information for clinical healthcare providers to deliver improved health education to patients and their children.Methods:Computer retrieval was implemented in PubMed, CINAHL, Embase, Web of Science, PsycINFO, Cochrane Library, ProQuest, China National Knowledge Infrastructure, and Wanfang Data. The search period was from January 1, 2000 to March 6, 2025. The literature was assessed according to the Joanna Briggs Institute (JBI) Center for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research. The JBI aggregative integration method was employed for the Meta-synthesis.Results:A total of nine articles were included. Thirty-two results were extracted, divided into ten categories, and integrated into five results, namely willingness to communicate illness, factors influencing communicating willingness, disease communication strategies, supporting children's coping, and perceptions of illness information.Conclusions:Disease communication between cancer parents and their minor children is influenced by multiple factors and exhibits complex diversity. Healthcare providers should fully understand and accurately recognize the distinct approaches of parents with cancer, offering guidance, advice, and encouragement whenever possible, and should dynamically provide timely medical support and assistance tailored to the evolving needs of patients throughout different stages of their disease treatment.
4.Meta synthesis of communication of diseases between cancer patients and minor children
Xiaoyu GUO ; Yingying LI ; Yuli LI ; Mengdi LIU ; Yanqiu GAO ; Zhenmei ZHANG
Chinese Journal of Modern Nursing 2025;31(34):4691-4698
Objective:To conduct evidence synthesis on disease communication between parents and their minor children from the perspective of parents with cancer, so as to provide information for clinical healthcare providers to deliver improved health education to patients and their children.Methods:Computer retrieval was implemented in PubMed, CINAHL, Embase, Web of Science, PsycINFO, Cochrane Library, ProQuest, China National Knowledge Infrastructure, and Wanfang Data. The search period was from January 1, 2000 to March 6, 2025. The literature was assessed according to the Joanna Briggs Institute (JBI) Center for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research. The JBI aggregative integration method was employed for the Meta-synthesis.Results:A total of nine articles were included. Thirty-two results were extracted, divided into ten categories, and integrated into five results, namely willingness to communicate illness, factors influencing communicating willingness, disease communication strategies, supporting children's coping, and perceptions of illness information.Conclusions:Disease communication between cancer parents and their minor children is influenced by multiple factors and exhibits complex diversity. Healthcare providers should fully understand and accurately recognize the distinct approaches of parents with cancer, offering guidance, advice, and encouragement whenever possible, and should dynamically provide timely medical support and assistance tailored to the evolving needs of patients throughout different stages of their disease treatment.
5.Exploration on the Mechanism of Yizhu Wendan Decoction in Treating Eczema Based on GEO Database Combined with Network Pharmacology and Experimental Verification
Yijie WANG ; Tingting GUO ; Yongjun LI ; Ziyi LI ; Meng ZHANG ; Mengdi SHI ; Shengnan GU ; Youpeng WANG ; Zhijun LI
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(4):32-41
Objective To explore the mechanism of Yizhu Wendan Decoction in treating eczema through GEO database combined with network pharmacology and experimental verification.Methods TCMSP,BATMAN-TCM and ETCM databases were used to screen the active components of Yizhu Wendan Decoction.Disease target information related to eczema was collected through GEO database.The drug-component-target network and PPI network were constructed by intersections of active component targets and disease targets.GO and KEGG pathway enrichment analyses were performed using DAVID database.CCK-8 method was used to screen out the optimal intervention concentration of freeze-dried powder of Yizhu Wendan Decoction.HaCaT cells were divided into control group,model group,Yizhu Wendan Decoction low concentration group,Yizhu Wendan Decoction high concentration group,si-IL-17RA group,si-IL-17RA+Yizhu Wendan Decoction low concentration group,si-IL-17RA+Yizhu Wendan Decoction high concentration group,Dexamethasone group,si-IL-17RA+Dexamethasone group.Each group was given relevant intervention.The expressions of chemokines and inflammatory factors were detected by qPCR.EdU and Annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis.Western blot was performed to detect the expressions of proteins related to apoptosis,skin barrier and IL-17 signaling pathway.Results By using databases,180 active components of Yizhu Wendan Decoction were obtained.Combined with GEO database microarrays related to eczema(GSE6012 and GSE57225),8 potential targets of Yizhu Wendan Decoction in the treatment of eczema were obtained.KEGG enrichment pathway mainly involved IL-17 signaling pathway,lipid and atherosclerotic,TNF signaling pathway,fluid shear stress and atherosclerotic,etc.When Yizhu Wendan Decoction freeze-dried powder concentration was 100 μg/mL,cell viability was the strongest.Yizhu Wendan Decoction could significantly inhibit the mRNA expressions of chemokines and inflammatory factors CCL17,CCL22,IL-1β,TNF-α,IL-6,IFN-γ,and increase the mRNA expression of IL-4 in eczema.It promoted the proliferation of HaCaT cells,increased the protein expression of Bcl-2,and reduced the protein expressions of Bad and Cleaved Caspase-3,thus inhibiting HaCaT cells apoptosis;promoted the protein expressions of FLG and LOR,and reduced the expression of MMP9,MMP1,CCL2,FOSL1,IL-17RA proteins in IL-17 signaling pathway.Conclusion Yizhu Wendan Decoction can treat eczema with multiple components,multiple pathways and multiple targets,promote the proliferation of HaCaT cells,inhibit their apoptosis,and restore the skin barrier.Its mechanism may be related to inhibiting the activation of IL-17 signaling pathway.
6.Fasudil inhibits Aβ1-42-induced microglial inflammatory response by inhibiting activation of NLRP3 inflammasome
Minfang GUO ; Peijun ZHANG ; Jingwen YU ; Tao MENG ; Yanhua LI ; Na LI ; Mengdi LI ; Yulu LI ; Lijuan SONG ; Jiezhong YU ; Cungen MA
Chinese Journal of Immunology 2024;40(9):1833-1837
Objective:To explore mechanism of Fasudil reducing Aβ1-42 induced BV2 cell injury based on NLRP3 inflamma-some.Methods:BV2 cells were divided into:normal control group,Aβ stimulation group,Aβ+Fasudil intervention group,Aβ+MCC950(NLRP3 inhibitor)intervention group.Cell morphology was observed under microscope.Cell activity was determined of by CCK8.NO release was measured by Griess.NLRP3,caspase 1 and IL-18 expressions were detected by immunofluorescence staining.NLRP3,ASC,caspase 1,IL-1β and IL-18 expressions were detected by Western blot.Results:Compared with normal control group,BV2 cells in Aβ stimulation group were activated and showed amoeba-like shape,cell activity was decreased,NO production was increased,NLRP3,ASC,caspase 1,IL-1β and IL-18 expressions were increased.Fasudil intervention and MCC950 intervention inhibited cell injury induced by Aβ1-42 in which BV2 cell morphology tended to be normal,cell activity was increased,while produc-tion of NO was reduced,and NLRP3,ASC,caspase 1,IL-1β and IL-18 expressions were down-regulated,there was no significant difference between Fasudil intervention group and MCC950 intervention group.Conclusion:Fasudil may alleviate Aβ1-42 induced BV2 cell injury and inflammatory reaction by inhibiting NLRP3 inflammasome activation.
7.Establishment of liver-specific Rbp4 knockout mice and analysis of glucose metabolism characteristics
Wanxian LU ; Qi MA ; Li WANG ; Mengdi LIU ; Baoping GUO
Acta Laboratorium Animalis Scientia Sinica 2024;32(4):493-502
Objective To establish a liver-specific Rbp4 gene knockout mouse model and to explore the effect of liver Rbp4 gene deletion on glucose metabolism.Methods Cre-LoxP technology was used to construct a liver-specific Rbp4 gene knockout mouse model using C57/BL6J and Alb-Cre mice.The genotype of the mice was identified by polymerase chain reaction and agarose gel electrophoresis.Ten 18 week old C57/BL6J male mice were included in the WT group,10 flox homozygous and Alb-Cre negative mice of the same age were included in the experimental control group(Rbp4flox/flox:Cre-),and 10 flox homozygous and Alb-Cre positive mice of the same age were included in the experimental group(Rbp4flox/flox:Cre+).Expression levels of RBP4 protein and mRNA in the liver were verified by Western Blot and quantitative reverse transcription-polymerase chain reaction(qRT-PCR),respectively,and expression levels of Rbp4 mRNA in other tissues were detected by qRT-PCR.Morphological changes in liver tissue were detected by hematoxylin and eosin staining.Blood glucose values were detected in mouse tail vein blood samples using a blood glucose meter,and glucose tolerance and insulin tolerance were determined.Expression levels of the liver glucose metabolism genes phosphoenolpyruvate carboxylase(Pepck)and glucose-6-phosphatase(G6pase)were detected by qRT-PCR.Results Liver-specific Rbp4 knockout mice were successfully bred and identified.RBP4 protein and mRNA levels were significantly decreased in the liver of Rbp4flox/flox:Cre+mice(P<0.05),but there was no significant difference in the relative expression levels of Rbp4 mRNA in fat,kidney,pancreas,spleen,heart,or muscle tissues among the three groups(P>0.05).Liver-specific Rbp4 knockout had no significant effect on liver morphology,glucose tolerance,or insulin tolerance(P>0.05).Pepck mRNA levels in the liver differed significantly among the three groups(P<0.05),and pairwise comparison showed that liver Pepck mRNA levels were significantly lower in Rbp4flox/flox:Cre+mice compared with levels in Rbp4flox/flox:Cre-mice(P<0.05).There was no significant difference in liver glucose-6-phosphatase(G6pase)mRNA expression among the three groups(P>0.05).Conclusions We successfully constructed a liver-specific Rbp4 knockout mouse model.Deletion of Rbp4 in the liver inhibited expression of Pepck mRNA in the liver,thus providing a basis for further exploration of the role of this gene in glucose metabolism in mice.
8.Study on molecular marker screening and evaluation of Rubi Fructus and its analogues
Mengdi ZHENG ; Lingling ZHANG ; Qi ZHANG ; Long GUO ; Xingjun WANG
International Journal of Traditional Chinese Medicine 2024;46(6):792-796
Objective:To standardize the origin of Rubi Fructus by using ITS2 and matK molecular markers to identify Rubi Fructus and its analogues. Methods:The ITS and matK sequences of Rubus chingii Hu, Rubus corchorifolius L.f., Rubus hirsutus Thunb., Rubus parvifolius L., Rubus buergeri Miq. and Rubus lambertianus Ser. were amplified and sequenced. The hidden Markov model was used to remove 5.8S and 28S from ITS sequences. A total of 25 ITS2 sequences were obtained. And a total of 22 matK sequences were obtained by proofreading by Glustal software. MEGA software was used for matK and ITS2 sequences analysis, intraspecific and interspecific genetic distances caculation, and neighbor joining (NJ) phylogenetic tree construction. ITS2 secondary structure was predicted by ITS2 database and aligned by 4Sale software. Profile neighbor-joining (PNJ) phylogenetic tree was constructed based on combined ITS2 sequence and its secondary structure by ProfDistS software. Results:An obvious barcoding gap between Rubi Fructus and its analogues was showed. The topological relationship between NJ tree and PNJ tree was consistent, and each taxon exhibits monophyly. The ITS2 secondary structure of Rubi Fructus was significant different from its analogues.Conclusions:It is recommended that both ITS2 and matK markers can serve as DNA barcodes for identifying Rubi Fructus and its analogues. The addition of ITS2 secondary structure information can enrich the identification results and provide theoretical support for resource research and variety selection of Rubi Fructus.
9.Serum free light chain level in patients with diabetic kidney disease and its correlation with renal function indexes
Chinese Journal of Postgraduates of Medicine 2022;45(11):1026-1030
Objective:To explore the correlation between the level of serum free light chain and renal function indexes in patients with diabetic kidney disease (DKD).Methods:The clinical data of 120 patients with DKD (study group) and 80 patients with simple diabetes (diabetes group) in the Beijing Sixth Hospital from October 2017 to October 2020 were retrospectively analyzed. Five ml of fasting peripheral venous blood were collected, the levels of serum uric acid, creatinine, homocysteine (Hcy) and free light chain (including free light chain κ, free light chain λ, ratio of free light chain κ and free light chain λ and total free light chain) were detected, and the estimated glomerular filtration rate (eGFR) was calculated. The correlation between total free light chain and renal function indexes in patients with DKD was analysis by Pearson method.Results:The free light chain κ, free light chain λ, ratio of free light chain κ and free light chain λ, total free light chain, uric acid, creatinine and Hcy in DKD group were significantly higher than those in diabetes group: (33.92 ± 9.06) mg/L vs. (17.65 ± 4.72) mg/L, (17.52 ± 2.83) mg/L vs. (9.81 ± 3.20) mg/L, 1.93 ± 0.23 vs. 1.80 ± 0.25, (51.44 ± 12.31) mg/L vs. (27.46 ± 7.92) mg/L, (383.69 ± 96.11) μmol/L vs. (345.93 ± 93.94) μmol/L, (117.57 ± 22.39) μmol/L vs. (75.06 ± 14.73) μmol/L and (17.64 ± 5.76) μmol/L vs. (11.66 ± 5.46) μmol/L, the eGFR was significantly lower than that in diabetes group: (103.95 ± 22.58) ml/(min·1.73 m 2) vs. (142.65 ± 26.50) ml/(min·1.73 m 2), and there were statistical differences ( P<0.01). Pearson correlation analysis results showed that serum total free light chain in patients with DKD was positively correlated with uric acid, creatinine and Hcy ( r = 0.707, 0.709 and 0.820; P<0.01), and negatively correlated with eGFR ( r = -0.730, P<0.01). Conclusions:The expression level of serum free light chain is obviously increased in patients with DKD, it has a certain correlation with renal function indexes. It can be used as one of the evaluation indicators for disease monitoring.
10.Classification and analysis of three types of blood donors based on local resident population
Chengcheng GUO ; Yuxiang CHEN ; Lin WANG ; Yifei WANG ; Mengdi MA ; Huiling MENG ; Ling HOU ; Wen LIU ; Shuanglin XUE ; Yufeng SUN ; Yang CHEN ; Linghua HOU ; Can HUANG ; Xiaoli CAO ; Xia HUANG
Chinese Journal of Blood Transfusion 2022;35(4):372-376
【Objective】 To provide reference for fine management of blood donors by classifying and analyzing different types of blood donors from domestic blood stations. 【Methods】 The resident population of 15 regions in China from 2016 to 2019 were taken as the research object, among which the blood donors were divided into three categories: age-eligible citizens, registered donors and donated donors. The average value and proportion of the three categories were calculated and statistically analyzed. 【Results】 The resident population of the 15 regions varied greatly. The mean 95% CI of the proportion of age-eligible citizens to resident population from 2016 to 2019 was (60.16%, 67.84%); registered donors to age-eligible citizens and resident population was (2.21%, 2.86%) and (1.41%, 1.79%), respectively; donated donors to registered donors, age-eligible citizens and resident population was (84.63%, 91.68%), (1.93%, 2.55%) and(1.23%, 1.59%), respectively. 【Conclusion】 There were differences in the number and proportion of different types of blood donors in different regions. The fine management of blood donors can help blood stations carry out more effective recruitment and retention strategies.

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