Objective To investigate the relationship between expression levels of membrane occupation and recognition nexus of linker domain protein 4(MORN4)and cluster differentiation 40 ligand(CD40L)in peripheral blood extracellular vesicles after percutaneous coronary intervention(PCI)and SYNTAX-Ⅱ score and prognosis in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods Retrospective analysis of 268 patients with acute STEMI who underwent PCI in the Department NO 2.of Cardiology,Affiliated Hospital of Shaanxi University of Chinese Medicine from June 2020 to May 2023.Patients were divided into MACE group and non MACE group based on major adverse cardiovascular events(MACE)occurred during the 1-year follow-up period.Quantitative real-time PCR(RT-qPCR)was used to detect the mRNA expression levels of MORN4 and CD40L in circulating extracellular vesicles in peripheral blood of the two groups.The clinical data and expressions of MORN4 and CD40L were compared between the two groups.Pearson correlation analysis of MORN4,CD40L and SYNTAX-Ⅱ scores.Multi-factor Logistics regression model was used to analyze the risk factors of MACE after PCI.The receiver operating characteristic(ROC)curve was plotted,the area under curve(AUC)was calculated,and the value of MORN4 and CD40L expression levels in predicting the occurrence of MACE was analyzed.Results Within 1 year after surgery,75 patients developed MACE.Clinical data comparison showed that the MACE group had higher numbers of diseased vessel branches,stent numbers,and SYNTAX-Ⅱ scores compared to the non MACE group,and the differences were statistically significant(χ2/t=4.451,2.625,11.553,all P<0.05).The expression levels of MORN4 mRNA(2.16±0.54)and CD40L mRNA(1.87±0.25)in the MACE group were higher than those in the non-MACE group(1.24±0.31,1.13±0.19),and the differences were statistically significant(t=17.429,26.092,all P<0.05).Pearson correlation analysis showed,MORN4 and CD40L expression were positively correlated with SYNTAX-Ⅱ score(r=0.548,0.523,all P<0.05).SYNTAX-Ⅱ score,MORN4 and CD40L expression were independent risk factors for MACE after PCI in patients with acute STEMI(Wald χ2=24.426,4.569,3.038,all P<0.05).When the cutoffvalues of MORN4 and CD40L were set to 1.79 and 1.52,respectively,their combined prediction of AUC(95%CI)sensitivity and specificity for MACE occurrence was superior to single indicator prediction(Z=1.972,2.393,all P<0.05).Conclusion The detection of MORN4 and CD40L expression in circulating extracellular vesicles of acute STEMI patients after PCI has a positive significance in evaluating the degree of coronary artery disease and the occurrence of MACE.The combined detection of MORN4 and CD40L has high clinical value in predicting the occurrence of MACE after surgery and can be used as effective molecular markers for evaluating the short-term prognosis of patients.

Objective To evaluate the prognostic predictive capability of a risk scoring model based on allograft rejection-related genes(ARRGS)in patients with hepatocellular carcinoma(HCC)and to validate the expression levels of the key gene Glomulin(GLMN)in HCC.Methods Expression data for HCC were downloaded from The Cancer Genome Atlas(TCGA)database,and ARRGS gene sets were obtained from the Misgdb database to construct ARRGS-related molecular subtypes.A prognostic model was developed using Lasso-Cox regression analysis,and its predictive performance was assessed through Kaplan-Meier survival analysis,time-dependent ROC curves,and internal validation.Twelve pairs of HCC tumor and adjacent non-tumor tissues were collected from patients who underwent radical surgery at Fuyang Minsheng Hospital between January 2020 and December 2023.The expression levels of GLMN in these samples were validated using Western blot(WB),real-time quantitative PCR(RT-qPCR)and immunohisto chemistry(IHC).Additionally,the correlation between GLMN expression and alpha-fetoprotein(AFP)levels in HCC patients were analyzed.Results Two molecular subtypes were identified based on ARRGS,with Cluster 1 demonstrating poorer prognosis and higher levels of immune infiltration.A prognostic model was constructed using ARRGS-related differentially expressed genes,including DYRK3,GLMN,MRPL3 and NME1,which exhibited robust predictive performance for 1-,3-and 5-year patient survival.In clinical samples,GLMN protein(t=4.275,P=0.023)and mRNA(t=8.313,P=0.003)levels were significantly elevated in tumor tissues,as confirmed by WB and RT-qPCR,and were strongly correlated with elevated AFP levels(r=0.688,P=0.028).Conclusion The ARRGS-based risk scoring model effectively predicts the prognosis of HCC patients.Elevated GLMN expression in HCC tumor tissues suggests its potential as a reliable diagnostic biomarker for HCC.

Objective To investigate the effect of atractylenolide Ⅱ regulated Yes associated protein(YAP)signaling pathway on joint function and splenic regulatory T cells(Treg)/helper T cell 17(Th17)expression in rheumatoid arthritis(RA)model rats.Methods The RA rat model was constructed,and SD rats were separated into a control group,a model group,a low-dose atractylenolide Ⅱ group(10 mg/kg/d),a high-dose atractylenolide Ⅱ group(50 mg/kg/d),and a high-dose atractylenolideⅡ+YAP activator(PY60)group.On the 1st,7th and 14th day of the dosing period,rats were weighed and the joint swelling rate was evaluated,the arthritis index was scored after administration;HE staining was applied to observe pathological changes;flow cytometry was applied to detect the proportions of Treg and Th17 cells in splenic tissue;Western blot(WB)was applied to detect the expression levels of phosphorylation(p)in metatarsal tissue-mammalian STE20-like protein kinase 1(p-MST1),MST1,phospho-large tumor suppressor gene 1(p-LATS1),LATS1,phospho-Yes associated protein(p-YAP)and YAP proteins.Results Compared with the control group,rats in the model group suffered from damage to the metatarsal cartilage tissue,resulting in weight loss and increased joint swelling rate during the administration period,during the administration period,the body weight was lower and the joint swelling rate was higher,the arthritis index score,Mankin score,proportion of spleen Th17 cells,and the expression level of metatarsal p-YAP/YAP protein were higher,the proportion of Treg cells and the expression levels of p-MST1/MST1 and p-LATS1/LATS1 proteins were lower,and the differences were statistically significant(t=4.953～38.268,all P<0.05).Compared with the model group,the cartilage tissue damage in the low and high dose atractylenolide Ⅱ groups was reduced,during the administration period,the body weight was higher and the joint swelling rate was lower,the arthritis index score,Mankin score,proportion of spleen Th17 cells,and the expression level of metatarsal p-YAP/YAP protein were lower,the proportion of Treg cells and the expression levels of p-MST1/MST1 and p-LATS1/LATS1 proteins were higher,the differences were statistically significant(tlow dose=4.050～17.013,thigh dose=6.379～32.174,all P<0.05).Compared to the high-dose atractylenolide Ⅱ group,the damage to the cartilage tissue of the metatarsal bone in the high-dose atractylenolideⅡ+PY60 group was worsened,during the administration period,the body weight was lower and the joint swelling rate was higher,the arthritis index score,Mankin score,proportion of spleen Th17 cells,and the expression level of metatarsal p-YAP/YAP protein were higher,the proportion of Treg cells and the expression levels of p-MST1/MST1 and p-LATS1/LATS1 proteins were lower,and the differences were statistically significant(t=5.084～27.703,all P<0.05).Conclusion Atractylenolide Ⅱ inhibits the activation of YAP signaling pathway,regulates splenic Treg/Th17 cell balance and ameliorates disease progression in RA rats.

Objective To investigate the relationship between microRNA(miR)-425-5p/patched homolog 1(PTCH1)axis molecules and clinical pathological parameters and prognosis in cancer tissues of primary laryngeal cancer(PLC)patients.Methods 102 PLC patients admitted to Mianyang Central Hospital from March 2020 to March 2021 were selected.The relative expression level of miR-425-5p and PTCH1 positive expression rate in PLC cancer tissues and adjacent normal tissues were compared,and the relationship between miR-425-5p relative expression level,PTCH1 positive expression rate and PLC clinical pathological parameters was analyzed.Kaplan-Meier curve and Log-Rank were used χ2 tests were conducted to analyze the 3-year cumulative survival rate of miR-425-5p and PTCH1 positive/negative expression groups,and COX regression model was used to analyze the influencing factors of PLC prognosis.Results Compared with normal tissue adjacent to cancer,the relative expression level of miR-425-5p in PLC cancer tissue was significantly increased(2.12±0.52 vs 0.98±0.17),and the positive expression rate of PTCH1 was significantly reduced(27.45%vs 61.76%),with statistical significance(t/χ2=21.045,24.302,all P＜0.05).Compared with patients with T1-T2,N0,and high differentiation of tumors,patients with T3-T4,N1-N3,and low differentiation of tumors showed a significant increase in the relative expression of miR-425-5p(t=3.647,2.900,3.029),and a significant decrease in the positive expression rate of PTCH1(χ2=5.842,4.011,5.136),the differences were statistically significance(all P<0.05).The 3-year cumulative survival rate of the miR-425-5p high expression group was 64.52%(20/31),which was significantly lower than that of the low expression group at 84.06%(58/69).The 3-year cumulative survival rate of the PTCH1 high expression group was 80.00%(28/35),which was significantly higher than that of the low expression group at 64.62%(42/65),and the differences were statistically significant(Log-Rank χ2=4.287,4.548,all P<0.05).Elevated T taging,cervical lymph node recurrence,elevated N staging,pharyngeal recurrence,elevated miR-425-5p,and negative PTCH1 expression were risk factors for poor prognosis of PLC(all P<0.05).Conclusion High expression of miR-425-5p and low expression of PTCH1 in cancer tissues of primary laryngeal cancer patients are significantly correlated with elevated T stage,low tumor differentiation,elevated N stage,and low 3-year cumulative survival rate.

Objective To investigate the value of serum ribosomal biogenesis factor nucleolar protein53(NOP53)mRNA and fibronectin type Ⅲ domain containing 1(FNDC1)mRNA in evaluating the efficacy of neoadjuvant chemoradiotherapy(NACRT)in patients with locally advanced rectal cancer.Methods A total of 140 patients with locally advanced rectal cancer who received NACRT treatment in Yulin Hospital the First Affiliated Hospital of Xi'an Jiaotong University from January 2020 to January 2023 were selected as the study group.According to the efficacy of NACRT treatment,they were divided into good response group(99 cases)and poor response group(41 cases).At the same time,70 healthy people were selected as control group.Real-time fluorescence quantitative PCR was used to detect serum NOP53 mRNA and FNDC1 mRNA levels in the two groups.Logistic regression analysis was used to analyze the factors affecting the efficacy of NACRT.The value of serum NOP53 mRNA and FNDC1 mRNA in evaluating the efficacy of NACRT for rectal cancer was analyzed by receiver operating characteristic analysis.Results The expression of serum NOP53 mRNA(3.21±0.36)and FNDC1 mRNA(2.73±0.34)in the study group was higher than that in the control group(0.61±0.17,0.72±0.18),and the differences were statistically significant(t=57.267,46.287,all P<0.001).The expression of serum NOP53 mRNA(4.08±0.43,4.10±0.40)and FNDC1 mRNA(3.62±0.39,3.40±0.39)in patients with T stage T4 and N stage N1+N2 rectal cancer was higher than that in patients with T stage T3(2.52±0.30,2.02±0.29)and N stage N0(2.21±0.31,1.02±0.30),and the differences were statistically significant(t=25.241～40.106,all P<0.001).The proportion of T stage T4(73.17%),N stage N1+N2(75.61%),serum NOP53 mRNA(5.56±0.39)and FNDC1 mRNA(4.42±0.38)in the poor response group were higher than those in the good response group(32.32%,43.43%,2.24±0.31,2.03±0.29),and the differences were statistically significant(t=12.045～53.337,all P<0.001).T stage T4,N stage N1+N2,high serum NOP53 mRNA,high serum FNDC1 mRNA were risk factors affecting the efficacy of NACRT for rectal cancer(Wald χ2=9.463～15.589,all P<0.001).The AUC of serum NOP53 mRNA combined with FNDC1 mRNA in evaluating the efficacy of NACRT for rectal cancer higher than predicted by serum NOP53 mRNA and FNDC1 mRNA alone,and the differences were statistically significant(Z=4.645,4.321,all P<0.001).Conclusion The levels of serum NOP53 mRNA and FNDC1 mRNA in patients with locally advanced rectal cancer are increased,which are related to the poor clinicopathological features of patients.Combined with serum NOP53 mRNA,FNDC1 mRNA can effectively predict the clinical efficacy of NACRT in patients with rectal cancer.

Objective To investigate the potential mechanism of tumor-derived exosome miR-3173-5p promoting the activation of cancer-associated fibroblasts(CAFs)and regulating the proliferation,invasion and apoptosis of non-small cell lung cancer(NSCLC)cells.Methods Exosome(Exo)of NSCLC cell A549 was extracted,the morphology of Exo was observed by transmission electron microscopy,and the expression of Exo marker protein was detected by Western blot.Real-time quantitative fluorescent PCR(qRT-PCR)was used to detect the expression of miR-3173-5p in A549 cells and Exo.The binding of miR-3173-5p to F-box/WD-40 domain protein11(FBXW11)was predicted by Starbase database,and verified by luciferase reporter gene analysis.Human lung fibroblast cell line(MRC-5)was treated with Exo and Exo inhibitor GW4869 or NC inhibitor/mimic or miR-3173-5p inhibitor/mimic and/or FBXW11 overexpression/empty vector,NC group,Exo group,Exo+GW4869 group,Exo-NC inhibitor group,Exo-miR-3173-5p inhibitor group,Exo-NC mimic group,Exo-miR-3173-5p mimic group,Exo-miR-3173-5p mimic+Vector group and Exo-miR-3173-5p mimic+FBXW11 group were set up respectively.The level of CAFs marker protein[Matrix metalloproteinase-9(MMP-9),α-Smooth muscle aorta(α-SMA),Chemokine(C-X-C motif)ligand 12(CXCL12),Fibronectin,Vimentin,Interleukin-1β(IL-1β),Interleukin-6(IL-6),Interleukin-8(IL-8)]in cells of each group was detected by Western blot analysis,and the influence of exosome miR-3173-5p and FBXW11 expression on CAFs activation was analyzed.Exo and Exo-miR-3173-5P mimic were separated and the supernatant of MRC-5 cells incubated with Exo-FBXW11 was used as conditioned medium(CM)to culture A549 cells.The NC-CM group,Exo-CM group,Exo-miR-3173-5p mimic-CM group and Exo-FBXW11-CM group were set up respectively.MTT assay,Transwell assay and flow cytometry were used to detect the effects of CAFs activation on proliferation,invasion and apoptosis of NSCLC cells.Results Transmission electron microscopy showed that the diameter of exosomal vesicles derived from NSCLC cells was about 30～100 nm.Western blot analysis showed that all exosome labeled proteins were positive.The expression of miR-3173-5p(33.45±3.16)in NSCLC-derived exosomes was significantly higher than that in tumor cells(1.01±0.07),and the difference was statistically significant(t=1.263,P<0.001).MiR-3173-5p targets FBXW11 and inhibits its expression.Compared with NC group,CAFs marker protein levels in Exo group were significantly increased(t=12.214～24.908),the expression of CAFs marker protein in Exo+GW4869 group was significantly inhibited compared with Exo group(t=13.160～25.143),the differences were statistically significant(all P<0.01),respetively.Compared with Exo group,miR-3173-5p inhibitor inhibited EXO-induced CAFs marker protein expression(t=11.059～21.094),and miR-3173-5p mimic promoted the expression of CAFs marker protein(t=12.943～18.671),the differences were statistically significant(all P<0.01),respectively.Overexpression of FBXW11 reversed the induction of CAFs activation by miR-3173-5p mimic.Compared with the NC-CM group,the proliferation activity and invasion rate of A549 cells in the Exo-CM group were significantly enhanced,and the apoptosis rate was significantly inhibited(t=10.207,2.359,3.001),miR-3173-5p mimic enhanced the promoting effect of Exo-CM on proliferation and invasion of A549 cells and the inhibitory effect on apoptosis(t=9.399,3.438,3.208),while overexpression of FBXW11 can antagonize the promotion effect of Exo-CM on proliferation and invasion of A549 cells and the inhibition effect on apoptosis(t=18.868,7.070,9.813),the differences were statistically significant(all P<0.05),respectively.Conclusion Tumor-derived exosome miR-3173-5p promotes CAFs activation through targeted inhibition of FBXW11 expression,further promotes proliferation and invasion of NSCLC cells,inhibits cell apoptosis,and regulates the occurrence and development of NSCLC.

Objective To study the effect of stachydrine on cardiomyocyte damage induced by high glucose(HG)and its regulation of Hippo-Yes-associated protein(YAP)signaling pathway.Methods Rat myocardial cells H9C2 were stimulated by HG with 30 mmol/L glucose to establish the myocardial cell injury model,and then treated with 0.05,0.10,0.15,0.20 mmol/L of stachydrine and their activities were detected by CCK-8 method,and the action concentration of stachycarine was screened.Then H9C2 was grouped into control(ctrl)group,HG group,low concentration stachydrine group,high concentration stachydrine group,and high concentration stachydrine+Hippo-YAP signaling pathway inhibitor(TDI-011536)group.Except for the ctrl group cultured with 5 mmol/L glucose,the other 4 groups were cultured with 30 mmol/L glucose,and the low and high concentration stachydrine groups were cultured with 0.05 and 0.10 mmol/L threonine for 24h,respectively.The high concentration stachydrine+TDI-011536 group were cultured with 0.10 mmol/L stachydrine and 3.00 μmol/L TDI-011536 for 24h.CCK-8 method was applied to detect cell proliferation.Flow cytometry was applied to detect apoptosis.ELISA were applied to detect the level of malondialdehyde(MDA)and superoxide dismutase(SOD).Western blot was applied to detect the level of phosphorylated YAP(p-YAP),YAP,proliferating cell nuclear antigen(PCNA),and B-cell lymphoma-2(Bcl-2)proteins.Results Compared with ctrl group,the survival rate of H9C2 cells induced by HG was significantly increased by 0.05,0.10,0.15,0.20 mmol/L stachydrine treatment,and the differences were statistically significant(t=8.32～29.67,all P<0.01).The 50%inhibitory concentration(IC50)value of stachydrine was about 0.09 mmol/L,and the concentrations of 0.05 mmol/L and 0.10 mmol/L close to and lower than IC50 were selected as the concentrations of hydrostachyine for subsequent experiments.Compared with the ctrl group,the survival rate in HG group was significantly decreased(t=44.32,P<0.01).Compared with HG group,the cell survival rate of low concentration stachydrine group and high concentration stachydrine group was significantly increased(t=10.06,21.66,all P<0.01).Compared with the high concentration stachydrine group,the cell survival rate in the high-concentration stachydrine+TDI-011536 group was significantly decreased(t=9.54,P<0.01),and the differences were statistically significant,respectively.Compared with ctrl group,the apoptosis rate of HG group was significantly increased(t=36.74,P<0.01).Compared with HG group,the apoptosis rate of low concentration stachydrine group and high concentration stachydrine group was significantly decreased(t=11.04,26.78,all P<0.01).Compared with the high concentration threonine group,the apoptosis rate of the high concentration stachydrine+TDI-011536 group was significantly increased(t=9.96,P<0.01),and the differences were statistically significant,respectively.Compared with ctrl group,SOD level in HG group was significantly decreased,MDA levels were significantly increased(t=18.85,29.12,all P<0.01).Compared with HG group,SOD level were significantly increased in low concentration stachydrine groups and high concentration stachydrine groups(t=6.59,9.86,all P<0.01),MDA level were significantly decreased(t=13.45,23.36,all P<0.01).Compared with the high concentration stachydrine group,the SOD level in the high concentration hydrostatin+TDI-011536 group was significantly decreased.MDA levels were significantly increased,and the differences were statistically significant(t=5.30,6.98,all P<0.01),respectively.Compared with ctrl group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein were significantly decreased,and the level of YAP protein was significantly increased(t=15.36～45.00,all P<0.01).Compared with HG group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein were significantly increased in low concentration stachydrine group and high concentration stachydrine group,the level of YAP protein levels were significantly decreased(t=5.51～25.15,all P<0.01).Compared with the high concentration stachydrine group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein in the high concentration hydrothreonine+TDI-011536 group were significantly decreased,the level of YAP protein significantly increased,the differences were statistically significant(t=4.27～11.25,all P<0.05).Conclusion Stachydrine may inhibit oxidative stress and apoptosis by activating Hippo-YAP signaling pathway,thereby ameliorating HG-induced myocardial cell damage.

Objective To investigate the effects of long non coding RNA(lncRNA)metastasis associated lung adenocarcinoma transcript 1(MALAT1)on the proliferation and osteogenic differentiation of human periodontal ligament stem cells(PDLSCs)by regulating the miR-150-5p/X-box binding protein 1(XBP1)axis.Methods Quantitative real-time PCR(qRT-PCR)was used to detect the expression of lncRNA MALAT1,miR-150-5p and XBP1 mRNA in undifferentiated and differentiated PDLSCs.The third generation PDLSCs were divided into control group,pcDNA group,pcDNA-lncRNA MALAT1 group,anti-miR-NC group,anti-miR-150-5p group,pcDNA-lncRNA MALAT1+mimic NC group and pcDNA-lncRNA MALAT1+miR-150-5p mimic group.The expression of lncRNA MALAT1,miR-150-5p and XBP1 mRNA of PDLSCs were detected by qRT-PCR.CCK-8 and the clone formation assay were used to detect the proliferation of PDLSCs.P-nitrophenolphosphate substrate method was used to detect alkaline phosphatase(ALP)activity.Alizarin red staining was applied to detect the formation rate of mineralized nodules.Western blot was used to detect XBP1,Cyclin D1,osteocalcin(OCN),Runt related transcription factor 2(RUNX2)and osteopontin(OPN)proteins.Dual luciferase assay was used to verify the targeting relationship between lncRNA MALAT1 and miR-150-5p,and between miR-150-5p and XBP1 was validated.Results Compared with the undifferentiated group,the expression of lncRNA MALAT1(1.95±0.14 vs 1.00±0.00)and XBP1 mRNA expression(1.63±0.12 vs 1.00±0.00)increased in the differentiated PDLSCs,the expression of miR-150-5p decreased(0.26±0.01 vs 1.00±0.00)in differentiated group,with the differences were statistical significance(t=16.622,12.860,181.262,all P<0.001).Overexpression of lncRNA MALAT1 or down-regulation of miR-150-5p could promote the proliferation and osteogenic differentiation of human PDLSCs(t=13.693～45.518),miR-150-5p mimic reversed the effects of overexpression of lncRNA MALAT1 on proliferation and osteogenic differentiation of PDLSCs(t=9.229～27.854),and the differences were statistically significant(all P<0.05),respectively.Dual luciferase assay confirmed that overexpression of miR-150-5P reduced the luciferase activity in transfected lncRNA MALAT1-WT and XBP1-WT cells(t=56.546,89.826,all P<0.001).Conclusion Overexpression of lncRNA MALAT1 may promote XBP1 expression by downregulating miR-150-5p,thereby promoting proliferation and osteogenic differentiation of human PDLSCs.

Objective To screening and validation of key genes for programmed cell death(PCD)in gout through bioinformatics and machine learning and immunoinfiltration analysis.Methods Gout-related datasets were obtained from the Gene Expression Omnibus(GEO)database,comprising the human gout dataset GSE160170 and murine gout dataset GSE190138,which served as the training cohort.Differentiall expression genes(DEGs)were screened with difference factor>2 and P<0.05.The DEGs of two data sets were intersected to obtain the common DEGs(co-DEGs).The co-DEGs were enriched by GO function and KEGG pathway analysis.The combination of co-DEGs and PCD related gene set was used to obtain PCD related DEGs.A PPI network was built in the STRING database.The key module genes were screened in Cytoscape's MCODE,the hub genes were screened in 12 algorithms built into the Cytohubba plugin,including Degree,MCC,DMNC,MCN,EPC,BottleNeck,EcCentricity,closness,Radiality,Betweeness,Stress and Clusteringcoefficoent,the common genes of the two was as candidate genes.The regression model of least absolute shrinkage and selection operator(LASSO)was used to screen key genes in the GSE160170 and GSE190138 data sets respectively,and the intersection of the two was adopted to obtain key genes.The diagnostic value of key genes in gout was evaluated by receiver operating characteristic(ROC)curve.The expression difference of gout related immune cells was investigated by single sample gene set enrichmemt analysis(ssGSEA)immunoinfiltration analysis.Finally,blood samples from 30 gout patients admitted to the Department of Rheumatology,Xi'an Fifth Hospital from February to April 2024 were collected as the experimental group,while blood samples from 30 healthy subjects were collected as the control group.RNA was extracted from the Peripheral blood mononuclear cell(PBMC).Quantitative real time polymerase chain reaction(RT-qPCR)was used to validate the expression of key genes in clinical samples.Results 53 common DEGs of GSE160170 and GSE190138 were obtained,among which 43 genes were up-regulated and 10 were down-regulated.GO and KEGG indicated that most genes were involved in cell death,apoptosis,interlenkin(IL)-17 signaling pathway,tumor necrosis facter(TNF)signaling pathway and nucleotide-binding oligomerization domain-(NOD)-like receptor signaling pathway.12 co-DEGs of programmed cell death and gout were obtained.A total of 7 candidate genes were screened.LASSO regression model screened 5 genes and 4 genes respectively in two datasets,and 3 key genes were abtained by the intersection of the two datasets,which were IL-6,plasminogen activator urokinase receptor(PLAUR)and NOD-like receptor thermal protein domain associated protein3(NLRP3).Validation within the training set revealed that all three genes attained perfect diagnostic performance for gout,with area under the ROC(AUC-ROC)curve values of 1.00.Immunoinfiltration analysis showed that the changes of activated CD4+T cells,activated CD8+T cells and natural killer cells were closely related to the occurrence and development of gout.In the clinical samples,compared with the control group,PLAUR,NLRP3 and IL-6 were highly expressed in gout patients,and the differences were statistically significant(t=18.852,9.633,8.293,all P＜0.05).Conclusion IL-6,PLAUR and NLRP3 provide potential biomarkers and therapeutic targets for the diagnosis and treatment of gout,offering new directions in this field.

Objective To investigate the relationship between the expression of Osteoglycin(OGN)mRNA and Axis inhibitory protein 1(Axin1)mRNA and Epithelial-mesenchymal transition(EMT)and prognosis in cervical cancer(CC).Methods 142 patients with CC who were treated in Yulin Hospital,the First Affiliated Hospital of Xi'an Jiaotong University from April 2019 to April 2021 were collected.Real time fluorogenic quantitative PCR(RT-qPCR)was used to detect the expression of OGN mRNA,Axin1 mRNA and EMT markers Snail mRNA,N-cadherin(N-cad)mRNA,Vimentin(Vim)mRNA.The expression of OGN and Axin1 protein was detected by immunohistochemistry(IHC).Pearson correlation analysis was used to analyze the correlation between OGN mRNA,Axin1 mRNA and EMT indicators Snail mRNA,N-cad mRNA,Vim mRNA.The effect of OGN and Axin1 protein expression on the survival of CC was analyzed by Kaplan-Meier(K-M)survival curve and COX model.Results Compared with adjacent tissues,the expression of OGN mRNA in CC cancer tissues(0.84±0.22 vs 2.01±0.38)was lower,and the expression of Axin1 mRNA(2.41±0.42 vs 1.02±0.33)was higher,the differences were statistically significant(t=31.752,31.010,all P<0.001).Pearson correlation analysis,the expression of OGN mRNA was negatively correlated with that of Snail mRNA,N-cad mRNA and Vim mRNA(r=-0.765,-0.703,-0.697,all P<0.001).The expression of Axin1 mRNA was positively correlated with that of Snail mRNA,N-cad mRNA and Vim mRNA(r=0.771,0.798,0.690,all P<0.001).Compared with adjacent tissues,the positive rate of OGN protein in CC cancer tissues was lower[28.17%(40/142)vs 88.03%(125/142)],and the positive rate of Axin1 protein was higher[69.01%(98/142)vs 11.27%(16/142)],the differences were statistically significant(χ2=73.185,98.535,all P<0.001).Compared with patients with ⅠA-ⅠB1 and no lymph node metastasis,the positive rate of OGN protein in cancer tissues of patients with International Federation of Gynecology and Obstetrics(FIGO)stage Ⅰ B2-Ⅱ A and lymph node metastasis was lower,and the positive rate of Axin1 protein was higher,and the differences were statistically significant(χ2=4.315～13.252,all P<0.05).The 3-year overall survival rates of OGN positive group and negative group were 90.00%(36/40)and 70.59%(72/102),respectively,and the difference was statistically significant(Log-Rankχ2=7.140,P=0.008).The 3-year overall survival rates of Axin1 positive group and negative group were 69.39%(68/98)and 90.91%(40/44),respectively,and the difference was statistically significant(Log-Rankχ2=9.061,P=0.003).Axin1 positive,FIGO stage IB2～ⅡB,lymph node metastasis were risk factors for poor survival of CC,and OGN positive was a protective factor(Wald χ2=6.250～12.278,all P<0.05).Conclusion OGN is down-regulated and Axin1 is up-regulated in CC,which are related to EMT indicators and adverse survival outcomes of CC patients.