1.An inductive learning-based method for predicting drug-gene interactions using a multi-relational drug-disease-gene graph.
Jian HE ; Yanling WU ; Linxi YUAN ; Jiangguo QIU ; Menglong LI ; Xuemei PU ; Yanzhi GUO
Journal of Pharmaceutical Analysis 2025;15(8):101347-101347
Computational analysis can accurately detect drug-gene interactions (DGIs) cost-effectively. However, transductive learning models are the hotspot to reveal the promising performance for unknown DGIs (both drugs and genes are present in the training model), without special attention to the unseen DGIs (both drugs and genes are absent in the training model). In view of this, this study, for the first time, proposed an inductive learning-based model for the precise identification of unseen DGIs. In our study, by integrating disease nodes to avoid data sparsity, a multi-relational drug-disease-gene (DDG) graph was constructed to achieve effective fusion of data on DDG intro-relationships and inter-actions. Following the extraction of graph features by utilizing graph embedding algorithms, our next step was the retrieval of the attributes of individual gene and drug nodes. In this way, a hybrid feature characterization was represented by integrating graph features and node attributes. Machine learning (ML) models were built, enabling the fulfillment of transductive predictions of unknown DGIs. To realize inductive learning, this study generated an innovative idea of transforming known node vectors derived from the DDG graph into representations of unseen nodes using node similarities as weights, enabling inductive predictions for the unseen DGIs. Consequently, the final model was superior to existing models, with significant improvement in predicting both external unknown and unseen DGIs. The practical feasibility of our model was further confirmed through case study and molecular docking. In summary, this study establishes an efficient data-driven approach through the proposed modeling, suggesting its value as a promising tool for accelerating drug discovery and repurposing.
2.Subacute exposure to DEHP leads to impaired decidual reaction and exacerbates the risk of early miscarriage in mice
Qiuju LIU ; Liping TAN ; Liu YUAN ; Xuemei CHEN ; Fangfang LI ; Junlin HE ; Rufei GAO
Journal of Zhejiang University. Medical sciences 2024;53(3):331-341
Objective:To investigate the effect of subacute exposure of Di(2-ethylhexyl)phthalate(DEHP)on endometrial decidualization and early pregnancy miscarriage in mice.Methods:CD1 mice were orally administrated with 300(low-dose group),1000(medium-dose group),or 3000 mg·kg-1·d-1 DEHP(1/10 LD50,high-dose group)for 28 days,respectively.An early natural pregnancy model and an artificially induced decidualization model were established.The uterine tissues were collected on D7 of natural pregnancy and D8 of artificially induced decidualization,respectively.The effects of a subacute exposure to DEHP on the decidualization of mice were detected by HE staining,Masson staining,TUNEL assay,and Western blotting.A model of spontaneous abortion was constructed in mice after subacute exposure to 300 mg·kg-1·d-1 DEHP,and the effect of impaired decidualization on pregnancy was investigated by observing the pregnancy outcome on the 10th day of gestation.Results:Compared with the control group,the conception rate was significantly decreased in the high-dose DEHP subacute exposure group(P<0.05).HE staining showed that,compared with the control group,the decidual stromal cells in the low-and medium-dose exposure groups were disorganized,the nuclei of the cells were irregular,the cytoplasmic staining was uneven,and the number of polymorphonuclear cells was significantly reduced.Masson staining showed that compared with the control group,the collagen fibers in the decidua region of the DEHP low-dose group and the medium-dose group were more distributed,more abundant and more disorderly.TUNEL assay showed increased apoptosis in the decidua area compared to the control group.Western blotting showed that the expression of BMP2,a marker molecule for endometrial decidualization,was significantly reduced(P<0.05 or P<0.01).The abortion rate and embryo resorption rate were increased,and the number of embryos,uterine wet weight,uterine area and placenta wet weight were decreased in DEHP low-dose group compared to the control group stimulated by mifepristone,an abortifacient drug(P<0.05 or P<0.01).Conclusion:Subacute exposure to DEHP leads to impaired endometrial decidualization during early pregnancy and exacerbates the risk of adverse pregnancy outcomes in mice.
3.Application of scenario simulation teaching combined with progressive cases in pediatric nursing teaching
Yuan BAI ; Chunfen WANG ; Xuemei WANG ; Xiaohui WEI ; Jiao LI
Chinese Journal of Medical Education Research 2024;23(11):1545-1549
Objective:To investigate the application effect of scenario simulation teaching combined with progressive cases in pediatric nursing teaching.Methods:A total of 60 nursing students who studied in Department of Pediatric Internal Medicine in Yan'an University Affiliated Hospital from July 2022 to November 2023 were selected as subjects, and according to the order of admission, they were divided into control group and observation group, with 30 students in each group. The students in the control group received traditional teaching, while those in the observation group received scenario simulation teaching combined with progressive case teaching. The two groups were assessed in terms of learning outcomes and degree of satisfaction with teaching. SPSS 22.0 was used to perform the chi-square test and the t-test. Results:There was a significant difference in theoretical assessment score between the control group and the observation group [(83.56±5.29) vs. (87.02±6.08), t=7.56, P=0.006]. Compared with the control group, the observation group had significantly higher scores of nursing operation proficiency, problem-solving ability, communication and coordination ability, emergency response ability, humanistic care, psychological care, and nursing service attitude ( P<0.001). Compared with the control group, the observation group also had a significantly higher total score and significantly higher scores of teaching contents, teaching arrangement, teaching effect, and overall learning gain ( P<0.001). Conclusions:The application of scenario simulation teaching combined with progressive cases in pediatric nursing teaching can effectively improve teaching quality and degree of satisfaction, enhance knowledge reserve and attitude of nursing interns, and promote the development of pediatric nursing.
4.Establishment and verification of reference intervals for blood cell ratios in apparently healthy people
Jingzhu NAN ; Xu ZHANG ; Hui YUAN ; Xuemei WEI ; Shuai ZHANG ; Chen WANG ; Xiujuan LI ; Honghao LU ; Xiaoran SHEN
International Journal of Laboratory Medicine 2024;45(19):2396-2402,2407
Objective To establish the reference intervals of neutrophil to lymphocyte ratio(NLR),mono-cyte to lymphocyte ratio(MLR)and platelet to lymphocyte ratio(PLR)in different genders and age groups in northern Chinese adults.Methods The data were analyzed according to the Clinical and Laboratory Stand-ards Institute C28-A3.Outliers were checked and judged according to the Dixon method.Subgroups were di-vided according to gender or age factors,and reference intervals were established for different subgroups.Ref-erence intervals were expressed as two-sided 95%percentiles.Results The reference intervals of NLR,MLR and PLR were 0.90-3.82,0.09-0.33 and 71.20-246.87,respectively.The results showed that NLR and PLR in men were lower than those in women(P<0.001),while MLR in men was significantly higher than that in women(P<0.001).Linear trend plots showed that NLR,MLR and PLR changed significantly in dif-ferent genders and age groups.In men,NLR and MLR increased with age,while PLR gradually increased and reached the peak before 50 years old,and gradually decreased after 50 years old.In women,NLR and MLR showed the lowest values at 50-<60 years old,while PLR reached the peak at about 50 years old.The refer-ence intervals established by the model set were verified,and the percentages beyond the reference intervals were less than 10%in different genders and age groups.Conclusion The reference intervals of NLR,MLR and PLR in different genders and age groups of healthy adults in northern China are established in the study.
5.Impact of non-alcoholic fatty liver disease on the outcome of patients with acute ischemic stroke
Xiaorong YU ; Cunsheng WEI ; Yuan CHEN ; Tingting YANG ; Xuemei CHEN
International Journal of Cerebrovascular Diseases 2024;32(5):333-337
Objective:To investigate the impact of non-alcoholic fatty liver disease (NAFLD) on the outcome of patients with acute ischemic stroke (AIS).Methods:Patients with AIS visited the Affiliated Jiangning Hospital of Nanjing Medical University between June 2017 and December 2023 were included retrospectively. At 3 months after onset, the modified Rankin Scale was used to evaluate the outcome, with scores of 0-2 defined as good outcome and >2 defined as poor outcome. Multivariate logistic regression analysis was used to determine the impact of NAFLD on the outcome of patients with AIS. Results:A total of 143 patients with AIS were enrolled, including 95 males (66.43%), aged 67.79±11.15 years. Ninety six patients (67.13%) had good outcome, and 47 (32.87%) had poor outcome. Multivariate logistic regression analysis showed that after adjusting for confounding factors, NAFLD was independently associated with the poor outcome in patients with AIS (odds ratio 2.500, 95% confidence interval 1.015-6.161; P=0.046). Conclusion:NAFLD is an independent risk factor for poor outcome in patients with AIS.
6.Application of urinary luteinizing hormone in the prediction of central precocious pu-berty in girls
Jinfang YUAN ; Xinli WANG ; Yunpu CUI ; Xuemei WANG
Journal of Peking University(Health Sciences) 2024;56(5):788-793
Objective:To evaluate the level of first morning voided(FMV)urinary luteinizing hor-mone(LH)in girls with breast development,and to determine the value of FMV urine LH in the evalua-tion of central precocious puberty(CPP).Methods:From September 2018 to April 2021,among the patients who were admitted to the Department of Pediatrics of Peking University Third Hospital for"pre-cocious puberty"and underwent gonadotropin-releasing hormone(GnRH)stimulation test,a total of 108 girls were enrolled.According to CPP diagnostic criteria,they were divided into CPP group(n=45)and non-CPP group(n=63).The clinical characteristics and hormone levels of the two groups were com-pared.Receiver operating characteristic(ROC)curve was used to analyze the cut-off value of FMV uri-nary LH in the diagnosis of CPP in girls.Further analyses were done to evaluate the value of FMV urinary LH in the diagnosis of CPP using correlation analysis between urinary LH level and common clinical cha-racteristics.Results:ROC curve analysis showed that FMV urine LH level was significant for the diagno-sis of CPP.The cut-off value of FMV urine LH was 0.69 IU/L(specificity 56.9%,sensitivity 85.0%,area under curve 0.804,P<0.001).The basic clinical characteristics without GnRH stimulation test were analyzed by binary Logistic regression analysis,indicating that the level of FMV urine LH,uterine volume,ovarian volume and advanced T-bone age had predictive significance for CPP diagnosis in girls(OR values were 2.125,1.961,1.564 and 2.672,respectively).The prediction model was established and the area under the ROC curve was 0.904,P<0.001.The level of FMV urine LH was positively cor-related with the levels of serum LH,FSH and estrogen before GnRH stimulation test,the peak value of blood LH after GnRH stimulation test,T bone age and uterine volume,with r values of 0.462,0.373,0.242,0.360,0.373 and 0.263,respectively,and P values were<0.001,<0.001,0.013,<0.001,<0.001 and 0.007,respectively.Conclusion:FMV urine LH can provide a good indication for the diagnosis of CPP.Combining with bone age advanced level and pelvic ultrasound measurement,the pre-dictive value of FMV urine LH can be further improved for the diagnosis of CPP in girls.
7.Construction of nursing quality evaluation criteria for orthopaedic trauma specialty
Jiahui LI ; Dan KONG ; Yuan GAO ; Wensu WANG ; Yu′e CHEN ; Xuemei CHEN ; Xiaojie FU
Chinese Journal of Practical Nursing 2024;40(9):665-672
Objective:To establish the evaluation criteria for the quality of nursing care in orthopaedic trauma specialties, and to provide a basis for scientific evaluation of the quality of nursing care in orthopaedic trauma specialties.Methods:From February to October 2023, John Hopkinson evidence-based method was used to synthesize the evidence, clinical investigation and semi-structured interview were used to draw up the "quality standard of nursing care in orthopaedic trauma specialty", and two rounds of Delphi method of expert inquiry were used to screen, demonstrate and calibrate the evaluation standard of nursing quality in orthopaedic trauma specialty.Results:The questionnaire recovery rate of 2 rounds of expert consultation was 100.00%, the coefficient of familiarity and authority of 2 rounds of expert consultation were 0.92 and 0.93. Through 2 rounds of expert letter consultation, the quality evaluation criteria of orthopaedic trauma specialist care were established, including 3 first-level indicators (structural quality, process quality and outcome quality), 22 second-level indicators and 85 third-level indicators.Conclusions:The process of constructing the evaluation standard of nursing quality in orthopaedic trauma specialty is scientific and reliable, which can provide standard guidance for clinical practice and is conducive to the development of specialized nursing.
8.Naringenin ameliorates insulin resistance in HepG2 cells by regulating high miR-29b expression
Yuan WANG ; Kaihong ZENG ; Xuemei YU ; Bo DENG
Acta Universitatis Medicinalis Anhui 2024;59(8):1423-1428
Objective To investigate the impact of naringenin(Nar)on insulin resistance(IR)in HepG2 cells and evaluate the role of mircoRNA-29b(miR-29b)expression in mediating this effect,thereby providing a foundation for further exploration into the mechanisms underlying naringenin's potential as a preventative and therapeutic agent for diabetes.Methods Insulin resistant HepG2(IR-HepG2)was established by stimulating HepG2 cells with 100 nmol/L insulin.Nar was treated with different concentrations(0,25,50,100 μg/ml)in IR-HepG2 cells.The effect of Nar on glucose consumption in IR-HepG2 cells was determined with glucose kit.miR-29b mimic and inhib-itor were transfected into IR-HepG2 cells of the 50 μg/ml Nar intervention group,and the expressions of insulin re-ceptor substrate-1(IRS-1),protein kinase B(Akt)/phosphorylated Akt(p-Akt),glucose transporter-4(GLUT4)genes and proteins in the insulin signaling pathway were detected by Real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-qPCR)and Western blot,respectively.Results Compared with IR-HepG2 model group,glucose consumption was increased in Nar intervention group with different concentrations(P<0.01),among which 50 μg/ml Nar intervention group was the most significant(P<0.001),and mRNA ex-pressions of IRS-1 and Akt were increased in Nar intervention group with different concentrations(P<0.05),the mRNA expression of IRS-1 and Akt in 50 μg/ml Nar intervention group was the most significantly increased(P<0.001),and GLUT4 mRNA expression in 50 μg/ml Nar intervention group was increased(P<0.05).The pro-tein expressions of IRS-1 and p-Akt were increased in different Nar concentration groups(P<0.001).Compared with IR-HepG2 model group,mRNA expression of IRS-1,Akt and GLUT4 and protein expression of IRS-1 and p-Akt were decreased in miR-29b mimic transfected cells(P<0.001),mRNA expression of IRS-1,Akt and GLUT4 and protein expression of IRS-1 and p-Akt were not different in miR-29b inhibitor transfection group,Nar interven-tion model group and Nar intervention transfected miR-29b mimic group increased the mRNA expression of IRS-1,Akt and GLUT4(P<0.001),and the protein expression of IRS-1 and p-Akt increased(P<0.05).Compared with Nar intervention model group,Nar transfected miR-29b mimic with Nar intervention did not change the mRNA expressions of IRS-1,Akt and GLUT4,while the protein expressions of IRS-1 and p-Akt were increased(P<0.05),Nar interfered with mRNA expression of IRS-1,Akt and GLUT4 and protein expression of IRS-1 and p-Akt in miR-29b inhibitor group(P<0.001).Conclusion Nar can increase glucose consumption in IR-HepG2 cells,increase the expression of IRS-1,Akt and GLUT4 genes,and increase the expression of IRS-1 and p-Akt proteins in IR-HepG2 cells.Nar increases the expression of IRS-1 and p-Akt in IR-HepG2 cells by inhibiting the overexpres-sion of miR-29b,and improves insulin resistance in HepG2 cells.Nar,as a plant compound,is expected to be a potential drug for the prevention and treatment of diabetes.
9.Correlation between serum beta 2-microglobulin level and cerebral microbleeds in the elderly
Cunsheng WEI ; Xiaorong YU ; Yuan CHEN ; Juan JI ; Xuemei CHEN
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(1):55-58
Objective To explore the correlation between serum beta 2-microglobulin(B2M)level and cerebral microbleeds(CMB)in the elderly.Methods A retrospective analysis of 636 elderly patients with chronic diseases admitted to the Department of Neurology of our hospital from Janu-ary 2020 to November 2022 was made.On the second day after admission,venous blood samples were collected to detect the serum B2M level,and brain magnetic resonance susceptibility weigh-ted imaging was performed.Then these patients were assigned into CMB group(82 cases)and CMB-free group(554 cases).Binary logistic regression analysis was employed to identify the inde-pendent risk factors for CMB.Results Binary logistic regression analysis showed that serum B2M level was an independent risk factor for CMB in elderly patients(Model 1:β=0.179,OR=1.196,95%CI:1.017-1.407,P=0.031;Model 2:β=0.215,OR=1.240,95%CI:1.048-1.468,P=0.012)after adjusting confounding factors.ROC curve analysis indicated that the optimal cutoff value of serum B2M level in diagnosing CMB was 1.805 mg/L,with a sensitivity of 70.7%and a specificity of 52.5%,and an AUC value of 0.657(95%CI:0.595-0.719,P<0.01).Conclusion The increment of serum B2M level is closely related to CMB in the elderly population,so the pro-tein can be used as one of indicators for prediction of CMB in the population.
10.Prediction of cognitive function in patients with cerebral small vessel disease based on morphological brain network connection model
Cunsheng WEI ; Yuan CHEN ; Zhenzhen HE ; Meng CAO ; Yusheng YU ; Xuemei CHEN
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(11):1320-1324
Objective To construct a morphological brain network in patients with cerebral small vessel disease(CSVD)and predict it application for cognitive function.Methods A total of 64 eld-erly CSVD patients admitted in our hospital from January 2020 to February 2024 were retrospec-tively recruited.Cognitive function was assessed with Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA).Their clinical data,and results of cognitive function and multi-modal MRI scanning were collected and analyzed.3D T1-weighted imaging based on Kullback-Leibler divergence similarity was used to construct individual morphological brain net-work,and the connectome-based predictive model was employed to construct a cognitive predic-tion model.Results The network,which is significantly and positively correlated with the MMSE and MoCA scores,was mainly located in the default mode network,and could effectively predict individual MMSE and MoCA scores(r=0.795,P=4.436×10-15;r=0.794,P=4.974×10-15,P<0.01).The connections,which were significantly negatively correlated with MMSE or MoCA scores,were mainly located between the salience/ventral attention network and other networks,and could also effectively predict individual MMSE and MoCA scores(r=0.766,P=1.679× 10-13;r=0.850,P=6.915×10-19,P<0.01).Combined positive correlation and negative correla-tion networks,the model showed further improved predictive performance(r=0.849,P=7.603 × 10-19;r=0.888,P=1.445 × 10-22,P<0.01).Conclusion Individual morphological brain network can effectively predict cognitive function in elderly CSVD patients,and can be used as a convenient tool for early warning of cognitive impairment related to CSVD.


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