Integrative analysis of bone-formation associated genes and immune cell infiltration in osteoporosis, and the prediction of active ingredients in targeted traditional Chinese medicine

Objective To explore the differential expression and mechanisms of bone formation-related genes in osteoporosis(OP)leveraging bioinformatics and machine learning methodologies;and to predict the active ingredients of targeted traditional Chinese medicine(TCM)herbs.Methods The Gene Expression Omnibus(GEO)and GeneCards databases were employed to conduct a comprehensive screening of genes and disease-associated loci pertinent to the pathogenesis of OP.The R package was utilized as the analytical tool for the identification of differentially expressed genes.Least absolute shrinkage and selection operator(LASSO)logis-tic regression analysis and support vector machine-recursive feature elimination(SVM-RFE)algorithm were employed in defining the genetic signature specific to OP.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses for the selected pivotal genes were conducted.The cell-type identification by estimating rela-tive subsets of RNA transcripts(CIBERSORT)algorithm was leveraged to examine the infiltra-tion patterns of immune cells;with Spearman’s rank correlation analysis utilized to assess the relationship between the expression levels of the genes and the presence of immune cells.Coremine Medical Database was used to screen out potential TCM herbs for the treatment of OP.Comparative Toxicogenomics Database(CTD)was employed for forecasting the TCM ac-tive ingredients targeting the key genes.AutoDock Vina 1.2.2 and GROMACS 2020 softwares were employed to conclude analysis results;facilitating the exploration of binding affinity and conformational dynamics between the TCM active ingredients and their biological targets.Results Ten genes were identified by intersecting the results from the GEO and GeneCards databases.Through the application of LASSO regression and SVM-RFE algorithm;four piv-otal genes were selected:coat protein(CP);kallikrein 3(KLK3);polymeraseγ(POLG);and transient receptor potential vanilloid 4(TRPV4).GO and KEGG pathway enrichment analy-ses revealed that these trait genes were predominantly engaged in the regulation of defense response activation;maintenance of cellular metal ion balance;and the production of chemokine ligand 5.These genes were notably associated with signaling pathways such as ferroptosis;porphyrin metabolism;and base excision repair.Immune infiltration analysis showed that key genes were highly correlated with immune cells.Macrophage M0;M1;M2;and resting dendritic cell were significantly different between groups;and there were signifi-cant differences between different groups(P<0.05).The interaction counts of resveratrol;curcumin;and quercetin with KLK3 were 7;3;and 2;respectively.It shows that the interac-tions of resveratrol;curcumin;and quercetin with KLK3 were substantial.Molecular docking and molecular dynamics simulations further confirmed the robust binding affinity of these bioactive compounds to the target genes.Conclusion Pivotal genes including CP;KLK3;POLG;and TRPV4;exhibited commendable significant prognostic value;and played a crucial role in the diagnostic assessment of OP.Resveratrol;curcumin;and quercetin;natural compounds found in TCM;showed promise in their potential to effectively modulate the bone-forming gene KLK3.This study provides a sci-entific basis for the interpretation of the pathogenesis of OP and the development of clinical drugs.

Dual Role of Wnt5a in the Progression of Inflammatory Diseases

Wnt5a is a secreted Wnt ligand that plays a critical role in cellular pathways and inflammatory diseases.The WNT5A gene encodes two protein isoforms,Wnt5a-long and Wnt5a-short,which differ based on different promoter methylation and have distinct functions.However,the mechanisms of the promoter methylation are unclear.Depending on the extent of promoter methylation,Wnt5a exerts both anti-inflammatory and proinflammatory effects in inflammatory diseases,which may be involved in different Wnt5a isoforms.Therefore,the Wnt5a isoforms may be potential diagnostic markers for inflammatory diseases and the mechanisms of the WNT5A gene promoter methylation need to be further investigated.

疗前FDG PET-CT标准摄取值预测直肠癌术后复发患者放疗疗效的价值

目的探究疗前FDG PET-CT标准摄取值(SUV)预测直肠癌术后复发患者放疗疗效的相关性。方法选取2016年1月~2017年6月在我院收治的直肠癌术后复发患者60例,治疗前对其进行FDG PET-CT检测,分析临床各病理参数与患者疗效和预后的相关性。结果患者3年生存率与年龄、淋巴结转移情况、浸润深度及癌胚抗原(CEA)具有明显相关性(P<0.05),与其性别和分化程度无相关性(P>0.05);经过多因素分析可知,影响患者生存的临床病理参数为淋巴结转移、浸润深度和FDG PET-CT标准摄取值(P<0.05)。结论 FDG PET-CT标准摄取值是影响直肠癌术后复发患者预后的重要因素,SUV值与患者放疗效果呈负相关关系,可以作为临床上对复发性直肠癌患者治疗及预后疗效判断的有效工具。

Extractum trametes robiniophila murr protects murine podocyte via actin cytoskeleton stabilization

The Chinese medicine Extractum trametes robiniophila murr(ETRM)is the extract of a type of fungus.Recent studies have suggested that ETRM efficiently improves the effacement of podocyte foot processes in adriamycin(ADR)-induced nephrotic rats.In the present study,we aimed to assess whether ETRM modulated the actin rearrangements of podocytes and involved signaling molecules,includingα-actinin-4 and nephrin.Podocytes were treated with ADR(0.5μmol/L),ADR(0.5μmol/L)+dexamethasone(Dex)(1μmol/L),ADR(0.5μmol/L)+ETRM(10 mg/mL).The F-actin in the podocytes was stained by fluorescent phallotoxins and observed by confocal microscopy.The expression levels ofα-actinin-4 and nephrin were tested by real-time PCR and Western blotting analysis.The administration of ETRM could significantly prevent ADR-treated podocytes from actin rearrangement.Both ETRM and Dex could stabilize podocyte actin cytoskeletons.Moreover,α-actinin-4 might act as a potential target for ETRM functionality in podocyte actin rearrangements.However,pretreatment with ETRM could not inhibit the up-regulation of nephrin as a result of ADR treatment.ETRM could improve the cytoskeleton stability in ADR-induced actin rearrangement of podocytes via regulatingα-actinin-4 expression.

改良中长导管逆向测量穿刺方法在乳腺癌患者中的应用

比较逆向测量与正向测量穿刺方法留置的改良中长导管留置时长及患者并发症发生情况。方法 本研究用方便抽样法选取了甘肃省某三甲医院乳腺科2021年1 ~ 6月乳腺癌患者80例为对照组,选取2021年7月至12月乳腺癌患者80例为实验组,对照组通过正向测量穿刺方法留置改良中长导管,实验组采用逆向测量方法留置改良中长导管,比较两组置管患者留置时间及导管相关并发症的发生情况。结果 实验组导管留置时间约为175天,对照组导管留置时间125天,差异有统计学意义(t=-7.10,P < 0.05)。实验组并发症发生率为3.75%,显著低于对照组的27.5%(P < 0.05)。结论 采用逆向测量穿刺方法的改良中长导管留置时间更长,能有效减少导管相关并发症的发生率,值得临床推广。