Desarrollo del repositorio de recursos educativos abiertos para la Universidad Virtual de Salud de Santiago de Cuba

La utilización de herramientas tecnológicas en la docencia condiciona el desarrollo de nuevas destrezas intelectuales en los estudiantes, lo que les facilita la aplicación de estrategias de investigación, mejora sus capacidades de una forma integral, les ayuda a enfrentar las dificultades y exigencias del mundo y les permite adquirir un aprendizaje más significativo para poder desenvolverse en el ámbito socioeducativo. Con vistas a cumplir lo anterior, se desarrolló un repositorio institucional de recursos educativos abiertos para la Universidad Virtual de Salud, a partir del empleo de herramientas tecnológicas libres y de código abierto que permiten la estandarización e interoperabilidad entre cada uno de los repositorios establecidos en el Sistema Nacional de Salud, con lo cual se garantizará una lógica de organización académica.

The use of digital technologies in teaching determines the development of new intellectual skills in students, which facilitates the application of investigation strategies, improves their capabilities in an integral way, helps them face the difficulties and demands of the current world and allows them to acquire more significant learning to have a good performance in the socio-educational environment. With a view to fulfilling the above, an institutional repository of open educational resources was developed for the Virtual Health University, based on the use of free and open-source technology tools that allow the standardization and interoperability among each of the repositories established in the National Health System, which will guarantee logic of academic organization.

Mining pharmacovigilance signals for asthma adverse events in underage population based on the FAERS database / 药物流行病学杂志

Objective To conduct data mining of asthma-inducing medications in underage populations based on the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,so as to provide reference for the clinical application of related medications.Methods Adverse drug event(ADE)reports from the first quarter of 2013 to the fourth quarter of 2022 in the FAERS database were collected and screened for reports of asthma adverse events in the this population(under 18 years old),which were categorized into infants,toddlers,children,and adolescents according to different age groups,and were subjected to medication signal mining by using the reporting odds ratio method,the composite standardized method,and the information component method.Results A total of 1 915 reports were obtained after screening,involving 1 042(54.41％)males and 831(43.39％)females;the highest percentage of the reporting population was between 12 and under 18 years old,with a total of 762(39.79％);60.78％of the reports were reported by health professionals;and the results of the clinical referrals showed that serious adverse events occurred in 85.90％of the cases.306 suspected drugs were screened,52 drugs were determined to be valid signals,and 1 044 adverse events were reported,of which 16 drug inserts did not mention the risk of asthma,in order of elosulfatase alpha,canakinumab,tobramycin,vancomycin,ceftriaxone,cetirizine,phenylephrine,imiglucerase,cefuroxime,betamethasone,atropine,tadalafil,riscovastatin,cyclophosphamide,octreotide,and omeprazole.Conclusion The FAERS database was mined for adverse drug event signals and evaluated using the proportional disequilibrium method to identify 16 medicines that may trigger pharmacogenetic asthma and are not documented in the specification,which can be used to provide a good early warning for the clinic.At the same time,focusing on special populations,strengthening the assessment of lung function before medication and monitoring during and after medication,timely interventions were taken to reduce the harm of drug-derived adverse reactions and ensure the safe use of medication.

Association of PPIs use with short-term and long-term mortality risk in patients with severe ischemic stroke:a retrospective cohort study based on the MIMIC-Ⅲ database / 药物流行病学杂志

Objective To investigate the association of proton pump inhibitors(PPIs)use with short-term and long-term mortality risk in patients with severe ischemic stroke.Methods This retrospective study based on the U.S.Medical Information Mark for Intensive Care Ⅲ(MIMIC-Ⅲ)database,ICU patients aged ≥18 years with the first ICU admission and a diagnosis of ischemic stroke were finally included in the study.All enrolled subjects were divided into PPIs group and non-PPIs group according to whether they had used PPIs(pantoprazole,lansoprazole and omeprazole)during hospitalization.Kaplan-Meier survival analyses and Cox regression models were used to analyze the association between the use of PPIs and the risk of ICU death,30 d risk of death,90 d risk of death in patients with severe ischemic stroke.Results A total of 1 015 patients were included,402 cases in the PPIs group and 613 in the non-PPIs group.The ICU-mortality,30 d and 90 d mortality were 15.37％,13.60％and 20.10％,respectively.Kaplan-Meier survival analyses illustrated that the PPIs group survived better than non-PPIs group in ICU mortality analysis(P=0.002).In Cox regression analysis,after adjustment for potential confounders,the hazard ratio(HR)for ICU mortality in the PPIs group relative to the non-PPIs group was 0.671 9(95％CI 0.478 8 to 0.942 8,P=0.021),but there was no significant difference between 30 d and 90 d mortality(P＞0.05).Conclusion In patients with severe ischemic stroke,the use of PPIs may be effective in reducing the risk of ICU death,but does not improve 30 d and 90 d risk of death in patients.

Data mining of hematological adverse events related to antibody-drug conjugate based on FAERS / 药物流行病学杂志

Objective Based on the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,data mining was conducted on hematological adverse events related to antibody drug conjugates(ADC),providing reference for the safe use of ADC drugs in clinical practice.Methods The report data from the third quarter of 2011 to the fourth quarter of 2022 were retrieved from the FAERS database.After data cleaning such as deduplication and name standardization,extract hematological adverse events related to ADC,and use report odds ratio method and the information component method for signal detection.Results A total of 101 610 adverse event reports were extracted,with 8 ADC drugs as the primary suspected drugs,and 5 768 ADC related hematological adverse event reports.Among them,3 423 cases of agranulocytosis were involved,and the signal intensity from strong to weak were sacituzumab govitecan(SG),gemtuzumab ozogamicin(GO),brentuximab vedotin(BV),polatuzumab vedotin(PV),enfortumab vedotin(EV),trastuzumab deruxtecan(TD),inotuzumab ozogamicin(IO)and ado-trastuzumab emtansine(TDM-1).There were 2 327 cases hematopoietic cell deficiency,with signals ranging from strong to weak were IO,SG,BV,EV,PV,TD,TDM-1,and GO.Report with clinical outcome of death of ADC drug related hematological adverse events included BV 179(16.84％),TDM-1 102(13.01％),TD 88(27.08％),GO 12(16.90％),IO 8(11.59％),EV 54(24.32％),PV 22(27.16％),and SG 84(21.05％).Adverse event time analysis showed that the number of events on the first day of TD,IO,and SG medication accounts for ≥ 40％of the total number of cases.The median time of hematological adverse events in TD,GO,IO,EV,PV,and SG was within one treatment course(21 days).Conclusion Attention should be paid to the risk of ADC drug-related hematological adverse event,during the clinical medication process,blood cell count changes should be closely monitored,and any abnormalities should be promptly diagnosed and treated.

Research on signal mining of adverse events of tizanidine based on FAERS database / 药物流行病学杂志

Objective Based on U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,the signal mining of tizanidine adverse drug events(ADEs)was conducted to explore the occurrence characteristics of ADE,hoping to provide references for the safe clinical application of tizanidine.Methods The reporting odds ratio(ROR)and medicines and healthcare products regulatory agency methods(MHRA)were used to analyse the ADE of tizanidine using FAERS registration data from the first quarter of 2004 to the second quarter of 2022.After valid signals were obtained,the MedDRA was used for translation and system organ classification.Results A total of 7 135 reports of tizanidine ADE were obtained,including 1 732 patients,1 304 ADE types were involved.According to the results of 2 ADE signal mining methods,at the preferred term(PT)level,177 signals were detected.There were 32 PT signals not included in the drug instructions,including potassium wasting nephropathy,cardio-respiratory arrest,and foetal growth restriction etc.In 1 732 patients,the number of ADE cases of female was 2.37 times that in male(1 057 vs.446),and the age group between 40 and 64 accounted for a large proportion(36.03％).The highest proportion(32.79％)reported by consumers.The system organ class involved mainly included various neurological diseases and psychosis.The median time to onset of tizanidine-related ADEs was 75 d(interquartile range:28-223 d),but it was necessary to be vigilant that ADE may still occur 1 year after starting the drug(13.38％).Conclusion This study aims to suggest that clinical application of tizanidin-related ADE should be paid full attention to the occurrence of ADE such as potassium-wasting nephropathy and suicidally completed,as well as key populations such as women and patients of 40-64 years old.

Application of Eurorad database in the teaching of radiology in standardized residency training: A case study of teaching film-reading / 中华医学教育探索杂志

The teaching of radiology in standardized residency training needs a large number of case data to strengthen the subjective understanding and awareness of residents. The database built by residency training bases can meet the needs of teaching to a certain extent, but the conditions of training bases vary across regions, which makes it difficult to achieve homogeneity in the teaching of radiology. This article discusses the application of Eurorad database in the teaching of radiology in standardized residency training. This database is free of charge, reliable, and comprehensive and provides a large number of free reliable cases and images for teaching, covering both common and rare diseases. Moreover, it can also be used to cultivate the English ability and comprehensive quality of residents and help to establish a hierarchical training system for radiology and non-radiology residents, thereby promoting the improvement in the quality of standardized residency training. This article shows the potential value of Eurorad database in the teaching of radiology in standardized residency training, and comparative studies are needed in the future to further prove its effectiveness.

Signal Mining Study of Adverse Reaction Associated with Allopurinol and Febuxostat Based on FDA Adverse Events Reporting System(FAERS)Database / 医药导报

Objective To conduct signal mining of adverse events(AEs)of allopurinol and febuxostat based on FAE-RS database,and to explore their potential drug risks and promote rational and safe clinical drug use.Methods The adverse event report data of febuxostat and allopurinol in 22 quarters from the first quarter of 2017 to the second quarter of 2022 were ex-tracted from FAERS database,and the signal mining of febuxostat and allopurinol adverse events(AE)was carried out using ROR method and PRR method.Results There were 5 060 AE reports for allopurinol,concentrated in patients aged≥60 years,in-volving 25 items of system organ classification(SOC),mainly in skin and subcutaneous tissue diseases(40.01%).It was found that 12 SOC categories were not mentioned in the instructions.For febuxostat,there were 905 AE reports,involving 17 SOC items,mainly in cardiac organ diseases(40.17%),and 2 items were not involved in the instructions.Allopurinol and febuxostat were as-sociated with infection and infectious diseases(5.51%,0.49%)and hepatobiliary diseases(5.35%,0.87%),However,these as-sociations were included in the instructions of allopurinol.Allopurinol was associated with the reproductive system and breast dis-eases(0.55%),pregnancy,puerperium and perinatal conditions(0.03%),but febuxostat was not found to be involved in the a-bove SOC.Conclusion The inclusion of adverse reactions in the instructions for allopurinol is relatively inadequate compared to buprostat,and the newly discovered involvement of systemic organs and AE can provide a reference for improving allopurinol in-structions.This study found that allopurinol and febuxostat allopurinol and febuxostat involved system differences,which can pro-vide reference for clinical individualized treatment.

A bibliometric analysis of research status and trends of simulated patients / 中国基层医药

To analyze simulated patient studies and their developmental trajectory, a comprehensive review was conducted using VOS viewer software. PubMed and CNKI databases were searched for 4 164 articles related to simulated patients. By creating keyword clouds and comparison tables, the current status and development trends of simulated patient studies at home and abroad were analyzed, and visual analysis was conducted based on these findings. Additionally, the analysis encompassed various metrics such as the number of published articles, journals, authors, and institutions involved. The findings reveal that the simulated patient studies focus on education, examination, and communication. Chinese studies on simulated patients initially demonstrated an upward trend but followed with a decline, whereas English studies have exhibited a steady upward trajectory. The application of simulated patients spans diverse fields including diagnostics, internal medicine, surgery, and medical practitioner exams, thereby greatly contributing to the advancement of medical education. It is anticipated that the number of simulated patient studies will continue to surge in the upcoming years.

Key genes and related pathways of hepatic fibrosis based on bioinformatics analysis / 局解手术学杂志

Objective By screening key genes and related pathways for hepatic fibrosis treatment through bioinformatics analysis,the differentially expressed genes of hepatic fibrosis patients were mined to predict potential therapeutic targets for liver fibrosis.Methods Gene expression profiles GSE197112 were obtained from GEO database.Differentially expressed genes were screened by Limma.DAVID online database was used to conduct GO enrichment analysis and KEGG signaling pathway enrichment analysis of differentially expressed genes.The protein-protein interaction(PPI)network diagram of differentially expressed genes were obtained from STRING database and visualize by Cytoscape software.At the same time,the plug-in CytoHubba in Cytoscape software was used to screen the target genes of hepatic fibrosis.Results A total of 399 differentially expressed genes were screened(P<0.01,∣log2FC∣>1.5),including 300 down-regulated genes and 99 up-regulated genes.These genes were mainly involved in GO biological processes such as mitosis checkpoint,DNA replication,chromosome segregation,cell division,apoptosis,adaptive immune response and so on,and mainly regulated the intestinal immune network for IgA production,progesterone-mediated oocyte maturation,human T-cell leukemia virus 1 infection,cell cycle,antigen processing and presentation,p53 signaling pathway,cancer transcription disorder,cell adhesion molecules and so on.Five target genes were screened by Cytoscape software:TTK,KIF2C,ASPM,DLGAP5,PBK.Conclusion In this study,399 differentially expressed genes and 5 target genes in hepatic fibrosis were screened by bioinformatics methods,which play key roles in the biological processes related to hepatic fibrosis,and provide a new direction for the pharmacological treatment of liver fibrosis.

lncRNA-mediated ceRNA network molecular mechanisms on ischemic stroke / 中国康复医学杂志

Objective:To construct the regulatory network of competitive endogenous RNA(ceRNA)and explore the mo-lecular mechanism of ischemic stroke(IS)by using bioinformatic analysis to screen the differentially-expressed genes. Method:The expression profiles of miRNA,mRNA and lncRNA in IS were downloaded from the NCBI GEO database.Differentially-expressed miRNAs,lncRNAs,and mRNAs were identified by the limma package in R software.The prediction of the relationship of lncRNA-miRNA and miRNA-mRNA were performed by starBase,miRDB and miRwalk databases.The results of prediction and differential analysis were taken to inter-sect and screened out differentially-expressed target mRNA(DETmRNAs),Kyoto Encyclopedia of Genes and Genomes(KEGG)and gene ontology(GO)enrichment analysis was performed by using the DAVID database.The protein-protein interaction(PPI)network was constructed by using the STRING database and the core tar-get genes in the network were identified by Cytoscape software. Result:A total of 20 differentially-expressed miRNAs,1512 lncRNAs,and 278 mRNAs were identified,and a ceRNA network was successfully constructed with the interactions of 5 lncRNAs-6 miRNAs-102 mRNAs in IS.The 285 DETmRNAs functions are mostly involved in the biological process such as chromatin organization,negative regulation of phosphoprotein phosphatase activity,or cell cycle.KEGG mainly enriched the signaling pathway including leukocyte trans-endothelial migration and platelet activation.The top 10 core genes were CREB1,MAPK1,GSK3B,SP1,PIK3R1,NR3C1,NCOR1,NFATC1,SETD2,and NSD1. Conclusion:The construction of the ceRNA network can help to further understand the molecular mechanism of IS and screen potential biomarkers,providing clues to further define rehabilitation targets and develop reha-bilitation strategies.

Screening and identification of core genes for diabetic nephropathy / 安徽医科大学学报

Objective @#To screen the core genes of diabetic kidney disease ( DKD) based on bioinformatics , ex- plore the therapeutic targets of DKD , and discuss its possible regulatory mechanism .@*Methods @#The expression da- ta matrix of glomerular transcriptome in patients with DKD in GEO database (GSE30528 , GSE47183) was extrac- ted , and the differentially expressed genes ( DEGs) were screened by bioinformatics methods to identify the core differential genes , and then gene expression and enrichment analysis (GSEA) were conducted to predict effective targets . @*Results @#By screening and identifying the mRNA expression matrix of DKD , five core genes were screened out. Among them , C1orf21 and NPHS1 were significantly down regulated , and CD48 , COL1A2 , and TGFBI were up regulated . NPHS1 and CD48 were significantly related to immune differences , intercellular communication , and cell surface interaction . Through receiver operating characteristic curve ( ROC) analysis and GSEA analysis and drug target prediction , it might be of great significance for the treatment of DKD .@*Conclusion @#The core genes screened in this study have significant correlation with DKD , which may be used as effective markers for the treat- ment of diabetes . And then , this study provides a theoretical basis for the treatment and identification of DKD .

A Preliminary Study on the Construction and Visualization of Knowledge Graph for the Ancient Chinese Medical Book Ling Shu / 广州中医药大学学报

Objective To explore the construction and visualization for knowledge graph of Ling Shu(Spiritual Pivot),with a view to providing ideas for the structured storage and display of the theoretical knowledge of the ancient Chinese medical books.Methods Using the professional idea of constructing knowledge graphs for reference,text mining technology was applied to construct the thesaurus,and then word division,entity recognition,and relationship extraction for the original text of Ling Shu were performed to get the elements of knowledge graph construction.The graph database Neo4j was used for the storage and query of the knowledge graph,and then the visual display of the knowledge graph was achieved.Results The 1 216 high-quality words consisting of the thesaurus of Ling Shu were obtained,and the construction of the knowledge graph of the theory of Ling Shu was realized.The constructed knowledge graph basically displayed the traditional Chinese medicine theories such as the correlation of visceral manifestations with essence qi,and the relationship between emotions and the five-zang organs described in Ling Shu,which made the retrieval and utilization of the related entities and relationships possible,and provided ideas for the structured storage and display of the theoretical knowledge of the ancient books of Chinese medicine.Conclusion The knowledge graph construction technology can be used to obtain the Chinese medicine theoretical knowledge graph of Ling Shu,and to display the knowledge connections of yin-yang and the five elements,and the internal organs and meridians expressed in the Ling Shu.The construction of the knowledge graph and its storage in the graph database enable the knowledge graph involved in the text of Ling Shu to be displayed in the form of visualized semantic network graph,and also make the embedding of other search systems such as the semantic search and semantic wiki possible,which will be helpful for the development of Chinese medicine intelligent medical services.

Establishment and application of the clinical case database in vascular surgery teaching / 基础医学与临床

Vascular surgery is an emerging clinical discipline with a wide range of categories and disease types.In theoretical teaching,a large amount of vivid imaging materials and vascular reconstruction photos are needed to effectively display the clinical manifestation.During internship training,there are not enough patients in the ward to cover common or frequently-occurring diseases of vascular surgery.As a result,development of a clinical case data-base is of great significance for the teaching of vascular surgery.This article mainly introduces the establishment and preliminary application of a clinical case database in vascular surgery teaching at Beijing Tiantan Hospital affiliated to Capital Medical University.

Survival prognosis of multiple malignant tumors with secondary primary esophageal cancer:a population-based analysis / 临床外科杂志

Objective To investigate the predisposing factors carried out in patients with secondary primary esophageal cancer and the related factors affecting its prognosis.Methods Patients with pathologically definite esophageal cancer diagnosis from 2000-2019 in the Surveillance/Epidemiology and End Results(SEER)database were selected,from which the data of patients with other malignancies as the first and esophageal cancer as the second primary(Secondary Primary Esophageal cancer-SPE)were screened,and logistic regression was used to analyze the independent risk factors in patients with secondary primary esophageal cancer,and the independent risk factors affecting the prognosis of such patients were analyzed by Cox proportional hazard model.Results A total of 13520 patients with multiple primary malignancies with esophageal cancer,including a total of 8308 patients with secondary primary esophageal cancer.Multiple logistic analysis showed that age,tumor site,tumor differentiation,pathological examines,SEER neoplasm invasiveness and regional lymph node adoption were independent factors influencing the occurrence of SPE,while multiple Cox risk proportion analysis suggested that age,year of diagnosis,race,tumor differentiation,SEER neoplasm invasiveness,surgery,chemotherapy,radiotherapy,and triple therapy were independent risk factors influencing SPE.Conclusion This study identified risk factors for secondary primary esophageal cancer,and surgery may be an effective treatment for SPE,which clinicians can use as a reference for diagnosis and treatment.

Construction of a genomic database for Group A Streptococcus and the analysis of prophage distribution / 中华实用儿科临床杂志

Objective:To illustrate the characteristics of the distribution of prophages among the Group A Streptococcus(GAS) by mining the existing whole genome sequencing of the GAS, performing bioinformatic analyses, extracting data about prophages, and analyzing the state of prophages in the genome and genetic composition of some prophages. Methods:It was a retrospective study.Genome assembly sequences of GAS reported in GenBank till May 2020 were collected, and the important background information of these strains was sorted out to create a local genomic database.A phylogenetic tree of the whole genome of GAS was conducted using the bioinformatics software.The core genome was analyzed, and potential prophages and their integrity in the genome were predicted to obtain the characteristics of the distribution of prophages.Genotype types, number of core genes, and number, length and carrying rate of prophages in the database for GAS were analyzed.Results:A database containing the genome sequence of 2 529 GAS strains was established, involving 140 emm genotypes.These strains were isolated from 19 countries from East Asia, Europe, America and Oceania.Stratified by the disease background, these strains were mainly divided into invasive infection, non-invasive infection and immune sequelae.Prophage analysis of 1 798 genomes showed that at least one complete prophage was detected in 1 366 (76.0%) genomes.The number of complete prophages of each strain ranged from 0 to 6, and the length ranged from 32.8 to 62.6 kb, which was mainly 30-40 kb in length.The phiHKUssa, phiHKUvir and phiHKU488 were the most common prophages present in dominant clones circulated in China in recent years, which mainly carried virulence genes like the speC, spd1 and ssa. Conclusions:Prophages are widely distributed in the genome of GAS, which are of great significance in the evolution and expansion of dominating clones and thus reshape the population structure within the emm genotype.The establishment of a local genome database provides important baseline data for molecular epidemiological surveillance.

Prediction and validation of potential targets for the glucagon-like peptide-1 receptor agonist in the treatment of Alzheimer's disease / 中国组织工程研究

BACKGROUND:In the process of exploring the mechanism of Alzheimer's disease,the important role of bioinformatics for common target screening has been revealed,enabling the use of its screening results as a basis for exploring the therapeutic effects of drugs on the disease. OBJECTIVE:To predict the targets of liraglutide,a glucagon-like peptide-1 receptor agonist,in the treatment of Alzheimer's disease by bioinformatics and molecular biology. METHODS:DisGeNET database and SEA database were used to obtain the common genes of Alzheimer's disease and liraglutide.GO/KEGG enrichment analysis of common targets was conducted using DAVID online database.Protein-protein interaction networks were constructed using STRING database.The optimal dosage of liraglutide was determined using cell counting kit-8 assay.Expression of key proteins was analyzed using immunofluorescence and immunoblotting techniques.The mouse hippocampal neuron HT22 cell line was used for ex vivo experiments,and the cells were randomly divided into three groups:HT22 group,HT22+Aβ group,and HT22+Aβ+Lir group.No special treatment was done in the HT22 group,while Aβ1-42 was used to intervene in the HT22 cell line for 24 hours to construct an Aβ injury cell model in the HT22+Aβ group.In additional to modeling,liraglutide was added to the HT22+Aβ+Lir group for 12 hours. RESULTS AND CONCLUSION:A total of 3 333 genes associated with Alzheimer's disease were screened from DisGeNET database.Then 147 potential targets of liraglutide were obtained from SEA database.Finally,64 common targets of Alzheimer's disease and Liraglutide were determined using R packets.GO/KEGG analysis of common targets using DAVID online database suggested that common targets were mainly enriched in the following biological processes:neuroactive ligand-receptor interaction,renin-angiotensin system,bladder cancer,endopeptidase activity,peptide receptor activity,G protein-coupled peptide receptor activity,and transport vesicles.The obtained 64 common target proteins were imported into SRTING online database for protein-protein interaction network construction,and the top three genes,matrix metalloproteinases 2,9 and interleukin 1β,were obtained.The activity of cultured cells was detected by the cell counting kit-8 kit.Liraglutide at 100 nmol/L was the optimal concentration for antagonizing Aβ1-42.In the western blot and immunofluorescence assays,the expression of matrix metalloproteinases 2,9 and interleukin 1β was significantly increased in the HT22+Aβ group compared with the HT22 group(P＜0.05)but significantly decreased in the HT22+Aβ+Lir group compared with the HT22+Aβ group(P＜0.05).To conclude,the above bioinformatics data and secondary validation of differential genes in the GEO database suggest that both matrix metalloproteinases 2,9 and interleukin 1β could be potential targets of liraglutide in the treatment of Alzheimer's disease.

Silent information regulator 1:A potential target of semaglutide in the treatment of Alzheimer's disease / 中国组织工程研究

BACKGROUND:Studies have found that glucagon-like peptide-1 and its analogues have a significant neuroprotective effect,and some drugs have been applied to the clinical stage Ⅲ study of Alzheimer's disease.However,the mechanism of its neuroprotective effect is still unclear,which needs to be further explored and clarified. OBJECTIVE:To screen out the genes related to the pathogenesis of Alzheimer's disease and the related targets of semaglutide for the treatment of Alzheimer's disease based on bioinformatics and network pharmacology analyses,to identify the potential target genes by comprehensive analysis of the two and to verify them at the cellular level. METHODS:Using DisGeNET database,differentially expressed genes between Alzheimer's disease patients and healthy population were screened out.The chemical structure formula and two-dimensional structure diagram of semaglutide were obtained using PubChem online database.GO/KEGG enrichment analysis was performed using DAVID online database.A protein-protein interaction network was constructed by using the STRING database.The HPA database was used to determine the distribution characteristics of the target proteins in various human tissues.Finally,western blot was used to detect relevant protein expression in HT22 cells after semaglutide intervention. RESULTS AND CONCLUSION:With the dataset in DisGeNET database,3 374 differentially expressed genes between Alzheimer's disease patients and healthy people were obtained,and meanwhile,101 target genes of semaglutide potential drugs were obtained.There were 23 intersection genes between them.Ten key genes were identified based on the protein-protein interaction network,which were silent information regulator 1(SIRT1),CASP9,CCND1,CASP1,KEAP1,DLG4,CASP4,GRB2,GRIA1,and EDNRA.The results of GO gene functional annotation analysis of key genes showed that the positive regulatory activity of cysteine endopeptidase,the positive regulation of proteolysis,and the positive regulation of cysteine endopeptidase involved the cytoplasmic part of the apoptotic activity process;AMPA glutamate receptor complex,inflammatory complex,CARD domain binding,cysteine endopeptidase activity,and cysteine endopeptidase activity were involved in the apoptotic process.The results of KEGG signaling pathway analysis indicated that colorectal cancer,non-small cell carcinoma,and endometrial carcinoma were related to immune infiltration,inflammation and autophagic apoptosis.In addition,according to the association ranking of key genes and their distribution in different tissues of HPA online database,SIRT1 was identified as the most significant differential gene.The expression level of SIRT1 protein was significantly down-regulated in HT22 cells after β-amyloid protein 1-42 treatment,but it could be significantly increased after being treated with semaglutide.To conclude,SIRT1 may be a target gene for semaglutide in the treatment of Alzheimer's disease.

Effects of conditioned medium of acute myeloid leukemia on biology of mesenchymal stem cells / 中国组织工程研究

BACKGROUND:At present,the biological functions and molecular changes of bone marrow mesenchymal stem cells in the tumor microenvironment of acute myeloid leukemia are still unclear. OBJECTIVE:To explore the changes in the biological function of bone marrow mesenchymal stem cells in acute myeloid leukemia and the role of acute myeloid leukemia conditioned medium by bioinformatics and experiment. METHODS:Differential genes were screened from GEO data sets,and enrichment analysis was performed.The protein-protein interaction network was constructed and the Hub gene was obtained.Bone marrow mesenchymal stem cells from patients with acute myeloid leukemia and healthy donors were cultured.Bone marrow mesenchymal stem cells from healthy donors were treated with acute myeloid leukemia conditioned culture solution.Each group was subjected to the adipogenic differentiation,osteogenic differentiation,staining of β-galactosidase,detection of the cell cycle,and validation of Hub genes. RESULTS AND CONCLUSION:(1)Gene expression data of bone marrow mesenchymal stem cells from acute myeloid leukemia patients and healthy donors were obtained from GSE84881,and 184 up-regulated genes and 140 down-regulated genes were screened.(2)The biological functions of enrichment mainly include cell cycle,adipocyte differentiation,cell metabolism,and MYC pathway.According to the Degree algorithm,10 up-regulated Hub genes and 10 down-regulated Hub genes were selected.(3)The cell in vitro experiment found that:compared with the control group,the surface antigen of acute myeloid leukemia mesenchymal stem cells did not change,but it showed enhanced lipid differentiation ability,weakened osteogenic differentiation ability,increased β-galactosidase positive cell number,altered cell morphology,arrested cell cycle,increased LGALS3 expression,and decreased MYC expression.Mesenchymal stem cells from healthy donors showed similar changes after being cultured in acute myeloid leukemia conditioned medium.(4)The results show that biological function of mesenchymal stem cells is altered in the acute myeloid leukemia microenvironment,which provides new insights into the interaction between mesenchymal stem cells and tumor cells.

Autophagy,ferroptosis-related targets and renal function progression in patients with chronic kidney disease:bioinformatics analysis and experimental verification / 中国组织工程研究

BACKGROUND:Autophagy and ferroptosis play important roles in the development of chronic kidney disease,but the molecular mechanisms and gene targets related to autophagy and ferroptosis in renal tissue of chronic kidney disease are still unclear. OBJECTIVE:To screen differentially expressed genes in chronic kidney disease-related datasets based on bioinformatics,and to explore potential key biomarkers suitable for screening renal function progression in patients with chronic kidney disease. METHODS:(1)The GSE137570 dataset was obtained from GEO database to screen the differentially expressed genes by Networkanalyst database analysis.Ferroptosis and autophagy related targets were obtained by OMIM,GENECARD,FerrDb and HAMdb databases.The respective data were intersected to obtain autophagy-ferroptosis related differentially expressed genes in chronic kidney disease for parallel enrichment analysis.The STRING website was used to construct the protein-protein interaction network of differentially expressed genes,which was imported into Cytoscape software and analyzed by MCODE and Cytohubba plug-in to screen potential core targets.Enrichment analysis was performed to obtain the functions of these potential core targets.(2)In the in vitro experiment,mouse renal tubular epithelial cells were divided into two groups:the control group received no intervention,while the model group was stimulated with 5 ng/mL transforming growth factor β1 for 24 hours to induce mesenchymal transformation of renal tubular epithelial cells.Flow cytometry was used to measure the levels of reactive oxygen species and changes in mitochondrial membrane potential in the cells.RT-PCR was employed to assess ferroptosis,autophagy-related markers,and the mRNA expression of potential core targets in the cells. RESULTS AND CONCLUSION:After screening the GSE137570 dataset,a total of 480 differentially expressed genes were obtained,including 104 upregulated genes and 376 downregulated genes(log2|(FC)|>1,P<0.05).There were 562 ferroptosis-related targets and 1 266 autophagy-related targets obtained from the OMIM,GENECARD,FerrDb,and HAMdb databases.Intersection of differentially expressed genes with ferroptosis-and autophagy-related targets yielded 15 ferroptosis-related targets and 18 autophagy-related targets,respectively.The enrichment analysis results indicate that ferroptosis-related differentially expressed genes are primarily involved in biological processes such as sulfur amino acid metabolism,neutrophil degranulation,and ferroptosis signaling pathways.Autophagy-related differentially expressed genes are mainly enriched in biological processes such as platelet degranulation,extracellular matrix degradation,and receptor tyrosine kinase signaling.After screened by MCODE and CytoHubba,key genes were identified in the protein-protein interaction network,including CD44,ALB,TIMP1,PLG,CCL2,and DPP4.Immune infiltration analysis results indicate that immune cells such as B cells,CD4+ T cells,NK cells,and monocytes show significant differential expression in renal tissue after chronic kidney disease,and the core targets are also significantly correlated with these immune cells(P<0.05).The results of receiver operator characteristic curve analysis further demonstrate that the pathological progression of chronic kidney disease can be effectively diagnosed by CD44,ALB,TIMP1,PLG,CCL2,and DPP4.Single-cell sequencing results show that,except for PLG,the expression of target genes in the renal tissue of mice in each model group is generally consistent with the results of this experiment.RT-PCR results demonstrate that,for the validation of autophagy and ferroptosis phenotypes,compared with the control group,the model group shows a significant decrease in mRNA expression of LC3B,Nrf2,and SLC7A11(P<0.05),and a significant increase in P62 mRNA expression(P<0.05).Regarding the validation of potential core targets,compared with the control group,the model group exhibits a significant decrease in mRNA expression of ALB and PLG(P<0.05),and a significant increase in TIMP1 and CCL2 mRNA expression(P<0.05).Overall,these findings indicate that,through bioinformatics analysis and experimental validation,CD44,ALB,TIMP1,PLG,and CCL2 are abnormally expressed in the renal tissue of patients with chronic kidney disease,closely correlated with estimated glomerular filtration rate and tubulointerstitial fibrosis,and maybe play a predictive role in the progression of chronic kidney disease.

Exploration and practice of improving the performance of hospital information systems with database integrated machine / 现代医院

Objective The rapid growth of data exchange and information volume in hospital information systems has brought significant challenges to the operation,maintenance,and service performance of the system.In order to overcome the performance bottleneck of the software and improve the response performance of the hospital information system,our hospital has tentatively introduced the Exadata database machine.Methods The machine was launched through hardware parameter selec-tion,high availability testing,and data migration.The benefits were evaluated by comparing the I/O operation time,SQL state-ment execution time,and business system module loading time before and after the launch.Results After using this machine,the overall waiting time of I/O operations decreased by 83.47% ,the execution time of the same statement decreased by over 22% ,and the average loadingtime of the business system decreased by43.74% .Conclusion The database machine can effec-tively reduce query time,accelerate the running speed of business modules,and help improve the performance of hospital infor-mation systems.