Objective To identify key genes and potential therapeutic drugs associated with Alzheimer's disease(AD)based on microglial senescence using bioinformatics analysis,providing new targets and insights for AD diagnosis and treatment.Methods Gene expression datasets related to microglial senescence and AD,specifically GSE62420 and GSE74615,were downloaded from the Gene Expression Omnibus(GEO)database.Differential Expressed Genes(DEGs)were identified using R software.Functional enrichment analysis,including gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,was performed using the DAVID online tool.The STRING database was used to construct the protein-protein interaction(PPI)network,and the CytoHubba plugin in Cytoscape software was applied to identify hub genes.The differential expression of hub genes was validated using the GSE129296 and GSE208386 datasets.Potential therapeutic drugs targeting these genes were predicted using the DSigDB database.Results A total of 35 DEGs,including 34 upregulated and 1 downregulated gene,were identified from the intersection of the GSE74615 and GSE62420 datasets.GO and KEGG enrichment analyses indicated that these DEGs were significantly involved in gene expression regulation,protein binding,metal ion binding,and the hypoxia-inducible factor 1(HIF-1)signaling pathway.PPI network analysis and CytoHubba screening identified ten hub genes:HIF1A,secreted phosphoprotein 1(SPP1),integrin alpha X(ITGAX),triggering receptor expressed on myeloid cells(TREM2),glycoprotein non-metastatic melanoma protein B(GPNMB),anexelekto receptor tyrosine kinase(AXL),Cystatin F(CST7),interleukin-12B(IL12B)、lipoprteinlipase(LPL)and fatty acid-binding protein 5(FABP5).Validation using the GSE129296 dataset showed that HIF1A,SPP1,ITGAX,TREM2,GPNMB,AXL,CST7 and FABP5 were significantly upregulated in microglia of AD mice,and the differences were statistically significant(t=8.411～29.49,all P<0.05).Further validation using the GSE208386 dataset indicated that LPL,SPP1,AXL and CST7 were significantly upregulated during microglial senescence,and the differences were statistically significant(t=4.755～5.964,all P<0.05).Based on these validation results,SPP1,AXL and CST7 were identified as key genes in AD.Drug prediction analysis using DSigDB revealed that potential therapeutic compounds targeting these genes exhibit anti-aging,anti-tumor,anti-inflammatory and DNA damage repair effects.Conclusion The key genes SPP1,AXL and CST7,identified based on microglial senescence,may serve as potential biomarkers for AD.Furthermore,multiple potential therapeutic drugs were predicted,offering new targets and strategies for AD diagnosis and treatment.

Objective To identify key genes and potential therapeutic drugs associated with Alzheimer's disease(AD)based on microglial senescence using bioinformatics analysis,providing new targets and insights for AD diagnosis and treatment.Methods Gene expression datasets related to microglial senescence and AD,specifically GSE62420 and GSE74615,were downloaded from the Gene Expression Omnibus(GEO)database.Differential Expressed Genes(DEGs)were identified using R software.Functional enrichment analysis,including gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,was performed using the DAVID online tool.The STRING database was used to construct the protein-protein interaction(PPI)network,and the CytoHubba plugin in Cytoscape software was applied to identify hub genes.The differential expression of hub genes was validated using the GSE129296 and GSE208386 datasets.Potential therapeutic drugs targeting these genes were predicted using the DSigDB database.Results A total of 35 DEGs,including 34 upregulated and 1 downregulated gene,were identified from the intersection of the GSE74615 and GSE62420 datasets.GO and KEGG enrichment analyses indicated that these DEGs were significantly involved in gene expression regulation,protein binding,metal ion binding,and the hypoxia-inducible factor 1(HIF-1)signaling pathway.PPI network analysis and CytoHubba screening identified ten hub genes:HIF1A,secreted phosphoprotein 1(SPP1),integrin alpha X(ITGAX),triggering receptor expressed on myeloid cells(TREM2),glycoprotein non-metastatic melanoma protein B(GPNMB),anexelekto receptor tyrosine kinase(AXL),Cystatin F(CST7),interleukin-12B(IL12B)、lipoprteinlipase(LPL)and fatty acid-binding protein 5(FABP5).Validation using the GSE129296 dataset showed that HIF1A,SPP1,ITGAX,TREM2,GPNMB,AXL,CST7 and FABP5 were significantly upregulated in microglia of AD mice,and the differences were statistically significant(t=8.411～29.49,all P<0.05).Further validation using the GSE208386 dataset indicated that LPL,SPP1,AXL and CST7 were significantly upregulated during microglial senescence,and the differences were statistically significant(t=4.755～5.964,all P<0.05).Based on these validation results,SPP1,AXL and CST7 were identified as key genes in AD.Drug prediction analysis using DSigDB revealed that potential therapeutic compounds targeting these genes exhibit anti-aging,anti-tumor,anti-inflammatory and DNA damage repair effects.Conclusion The key genes SPP1,AXL and CST7,identified based on microglial senescence,may serve as potential biomarkers for AD.Furthermore,multiple potential therapeutic drugs were predicted,offering new targets and strategies for AD diagnosis and treatment.

Objective To investigate the distribution of virulence genes of Klebsiella pneumoniae(KPN)and to evaluate the diagnostic efficacy of peg-344 for hypervirulent strains.Methods KPN isolates were col-lected from January to December in 2023 in Xuanwu Hospital,Capital Medical University.Whonet5.6 was used to analyze the distribution and drug resistance of bacterial strains.Toxicity testing included wire string test,PCR amplification of virulence genes(peg-344,rmpA,iutA,iroB),K1 and K2 capsule serotypes,serum resistance test,and diagnostic efficacy of detection was analyzed by using receiver operating characteristic curve.Results A total of 122 KPN isolates were collected,including 45(36.9%)sensitive strains,20(16.4%)extended-spectrum β-lactamase positive strains,and 57(46.7%)carbapenem-resistant Klebsiella pneumoniae strains.The specimens were mainly isolated from sputum,urine,and blood,and mainly came from Department of Urology,Department of Neurology,Intensive Care Unit,and Department of Neurosurgery.The positive rate of string test was 27.9%.PCR detected K1(12.3%),K2(8.2%),peg-344(62.3%),rmpA(60.7%),and iutA(73.8%),but the iroB result was negative,and strains with multiple virulence genes accounted for 63.1%.The results of the serum resistance test showed that 43.5%,31.1%,and 25.4%of the samples were at levels 1-2,3-4,and 5-6,respectively.peg-344 had the largest area under the curve for diagnosing the hy-pervirulent strains,followed by peg-344+iutA and peg-344+rmpA.Conclusion KPN is widely distributed in the hospital,and there are a variety of virulence genes.peg-344 has clinical value in distinguishing low viru-lence from high virulence in KPN.

Objective To investigate the expression level and diagnostic value of serum DNA polymerase α(DNA pol α)in Alzheimer's disease(AD),and analyze its diagnostic efficacy in AD.Methods A total of 100 patients of dementia of Alzheimer's type(DAT)and 43 patients of mild cognitive impairment(MCI)from Xuanwu Hospital Capital Medical University from March 2019 to April 2023 were included in this study,and 68 healthy individuals of the same age group were collected as the HC group.The expression level of DNA pol α was detected in each group,and the diagnostic value of DNA pol α in AD was analyzed by receiver oper-ating characteristic(ROC)curve.Results The expression level of DNA pol α in DAT group was higher than those in the MCI group(P＜0.05)and the HC group(P＜0.001).The expression level of DNA pol α showed an increasing trend as AD progressed.The expression level of DNA pol α was negatively correlated with Mini Intelligent Mental State Examination Scale(MMSE)score and Montreal Cognitive Assessment Scale(MoCA)score(r=-0.155 3,-0.203 7,P＜0.05).The area under the curve(AUC)of DNA pol α for diagnosing DAT was 0.682,and the sensitivity was 0.900.The AUC for diagnosing MCI was 0.546,and the sensitivity was 0.977.The AUC for differential diagnosis of MCI and DAT was 0.664,the sensitivity was 0.780,and the specificity was 0.535.Conclusion The expression level of DNA pol α is significantly increased in AD patients with DAT,and its expression level is related to the progression of AD,suggesting that DNA pol α has the pos-sibility to be a potential blood biomarker for the diagnosis of AD.

Alzheimer's disease(AD)is one of the most common types of dementia in clinical practice.The increased permeability of the gut and blood-brain barrier caused by intestinal microecological dysbiosis may be an important incentive to affect the incidence of AD.Gut microbiota regulates the central nervous system through the gut microbiota-gut-brain axis(gut-brain axis),and plays an important role in the cognitive func-tion,occurrence and development of clinical symptoms in AD patients.This review comprehensively reviewed the current literature on the relationship between gut microbiota dysregulation and inflammatory cytokine changes in AD,and the treatment of AD targeting with gut microbiota,so as to clarify the new progress in the influence of intestinal microecology changes on the cognitive function of AD patients,the potential diagnosis in the early onset of AD,and the potential mechanism of gut microbiota participating in the regulation of AD.It provides a new idea for the treatment strategy of AD.

Stroke is an acute cerebrovascular disease, and a group of diseases that cause brain tissue damage due to sudden rupture of brain blood vessels or blockage of blood vessels, mainly including ischemic stroke and hemorrhagic stroke. In recent years, although some progresses have been achieved, there are still few biomarkers that can be used for effective warning and monitoring for people at high risk of stroke. Omics research is an important research strategy for discovering differential genes, molecules, and epigenetic markers in the process of disease occurrence and development. A systematic summary of progress made in recent years, in stroke genomics, transcriptomics, proteomics, and metabolomics in recent years, as well as their potential applications in stroke warning, diagnosis, and monitoring, was systematically discussed in the presence review, in order to provide reference for future research on stroke biomarkers.

Objective To investigate the risk factors for the formation of infectious stones among residents in western Fujian Province and construct a nomogram model for preoperative prediction of the risk of infectious stones. Methods Clinical data of 204 patients who received treatment for urinary tract stones at Longyan People′s Hospital Affiliated to Xiamen Medical University from October 2021 to November 2023 were analyzed. All patients underwent stone composition analysis. Univariate and multivariate Logistic regression analysis were used to screen independent risk factors for infectious stones, construct a nomogram model for predicting the risk of infectious stones, and the discriminative power and accuracy of the model was evaluated. Results Based on the results of stone composition analysis, 204 patients were divided into infectious stone group(56 cases) and non-infectious stone group(148 cases). Univariate and multivariate Logistic regression analysis showed that female (OR=2.602, 95%CI, 0.766 to 8.842, P=0.039), diabetes (OR=9.751, 95%CI, 2.547 to 17.332, P=0.001), long diameter of stones (OR=1.123, 95%CI, 1.046 to 4.207, P=0.031), moderate to severe hydronephrosis (OR=4.173, 95%CI, 1.256 to 13.865, P=0.020), high urine pH value (OR=6.078, 95%CI, 1.922 to 19.216, P=0.002), and positive urine culture (OR=6.060, 95%CI, 1.398 to 16.262, P=0.016) were independent risk factors for infectious stones. A nomogram model for predicting the risk of infectious stones was constructed based on independent risk factors. The area under the curve of this model for predicting infectious stones was 0.860, which was significantly larger than the area under the curve predicted by gender, diabetes, stone long diameter, degree of hydronephrosis, urine pH value, and urine culture results (P < 0.05). The model was validated by 1 000 internal resampling, with an average absolute error of 1.8%, indicating a high consistency between the predicted risk of infectious stones and the actual situation. Conclusion Female, diabetes, long diameter of stones, moderate to severe hydronephrosis, high urine pH value, and positive urine culture are independent risk factors for infectious stones among residents in western Fujian Province. The nomogram model constructed based on these factors can predict the risk of infectious stones preoperatively with high predictive efficiency.

Alzheimer disease (AD) is the most common cause of dementia, and its early diagnosis is of great importance to delay the disease and improve the prognosis. Compared with cerebrospinal fluid, blood tests have the advantages of being less invasive and easier to obtain. In recent years, with the application of ultrasensitive detection technology, the diagnostic value of blood markers for AD has been continuously explored, which is expected to provide more direct and effective evidence for early diagnosis and early intervention of AD.

Alzheimer disease (AD) is a neurodegenerative disease in the elderly. Early intervention is the only reliable means to delay the progress of the disease. Referring to the diagnostic criteria of AD, this paper summarizes and analyzes the representative literatures of various AD biomarkers derived from cerebrospinal fluid in recent years, and reviews the efficacy of various cerebrospinal fluid biomarkers in the diagnosis and differential diagnosis of AD. Results show that CSF Aβ42, Aβ42/Aβ40, T-tau, p-tau, Aβ42/p-tau, growth-associated protein 43, synaptosomal-associated protein 25, neurogranin and visinin-like protein-1 are of great value in the diagnosis and differential diagnosis of AD. The above CSF biomarkers can be used in the diagnosis and differential diagnosis of AD. The laboratory should select appropriate AD CSF biomarkers according to its own conditions in daily laboratory works.

Objective:To explore the age-related changes of Pole2 expression levels in peripheral blood lymphocytes of healthy people, and analyze the differences of Pole2 expression levels in peripheral blood lymphocytes of four common senile disease patients between normal peers.Methods:Healthy people and patients in the physical examination center of Xuanwu Hospital of Capital Medical University from December 2018 to December 2019 were selected as the research objects, the mRNA and protein level of Pole2 in heathy individual as 20-29,30-39,40-49,50-59,60-69,70-79 y were checked by RT-PCR and Western blot,and the age-related curve was drew. The mRNA and protein expression levels of Pole2 were also detected in the peripheral blood lymphocytes of patients of DM,CHD,AD,CVD. And the deviation with healthy people of the same age was analyzed from one way ANOVA and repeated measurement were used to compare the mean of multiple groups.Results:The mRNA and protein levels of Pole2 increased in the lymphocytes of healthy people at 20-29 y and 50-59 y grouy, and decreased after 60-69 y and 70-79 y ( P<0.001). The Pole2 levels of mRNA and protein in the lymphocytes of patients of CHD,AD,DM and CVD cerebral atherosclerosis were significantly higher than that of healthy people of the same age. Moreover, the Pole2 level of lymphocytes of AD patients was significantly higher than that of other patient groups ( P<0.001). Conclusion:The expression level of Pole2 in peripheral blood lymphocytes increases with age before the age of 60 years old and decreases with age after 60 years old ;and the expression in four common senile diseases was higher than that in normal people.