Study on Serum WWP1 and NLRP3 Expression Levels and Their Clinical Value in Patients with Heart Failure with Preserved Ejection Fraction / 现代检验医学杂志

Objective To investigate the expression level and clinical significance of WW domain-containing E3 ubiquitin protein ligase 1(WWP1)and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)in patients with heart failure with preserved ejection fraction(HFpEF).Methods A total of 153 patients with HFpEF admitted to Fengfeng General Hospital of North China Medical and Health Group from January 2021 to September 2022 were collected as the observation group.According to the New York Heart Association(NYHA)cardiac function grading of patients,they were grouped into cardiac function grading Ⅰ～Ⅱ group(n=64)and cardiac function grading Ⅲ～Ⅳ group(n=89),while 148 healthy volunteers were collected as the control group.The correlation between serum WWP1 and NLRP3 levels and cardiac function indexes of patients was explored by Pearson analysis.The diagnostic value of serum WWP1 and NLRP3 levels on the severity of heart failure in HFpEF patients was analyzed by the receiver operating characteristic(ROC)curve.Results Compared with the control group,the expression levels of WWP1(1.68±0.35 vs 1.04±0.19)and NLRP3(6.72±1.26 ng/ml vs 4.57±0.84 ng/ml)in the observation group were significantly increased,and the differences were statistically significant(t=19.623,17.359,all P<0.05).Compared with grade Ⅰ to Ⅱ groups,WWP1(1.87±0.39 vs 1.42±0.32)and NLRP3(7.53±1.40 ng/ml vs 5.59±1.18 ng/ml)expression levels in grade Ⅲ to Ⅳ groups were significantly increased and the differences were statistically significant(t=7.744,9.017,all P<0.05).The differences of heart rate,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD),left ventricular end-diastolic diameter(LVEDD),left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD),left ventricular end-diastolic posterior wall thickness(LVPWT),left ventricular ejection fraction(LVPWT),left ventricular ejection fraction(LVEF),peak mitral early diastolic velocity(E)/peak late diastolic velocity(A)and the incidence of atrial fibrillation between the cardiac function grade Ⅰ to Ⅱ groups and the grade Ⅲ to Ⅳ groups were significant(t/χ2=2.757～7.069,all P<0.05).Serum WWP1 level in HFpEF patients was positively correlated with LAD,LVEDD and LVPWT(r=0.547,0.471,0.536,all P<0.05),and negatively correlated with LVEF and E/A(r=-0.485,-0.417,all P<0.05).Serum NLRP3 level was positively correlated with LAD,LVEDD and LVPWT(r=0.534,0.494,0.520,all P<0.05),and negatively correlated with LVEF and E/A(r=-0.462,-0.523,all P<0.05).ROC results showed that the area under the curve(AUC)of serum WWP1 and NLRP3 levels alone for diagnosing the severity of heart failure in HFpEF patients was 0.825 and 0.855,respectively,and the AUC(0.924)diagnosed by the combination of the two was significantly greater than that diagnosed by the serum WWP1 alone and the AUC diagnosed by the NLRP3 alone(Z=3.600,P<0.001;Z=3.053,P=0.002).Conclusion The levels of serum WWP1 and NLRP3 were increased in patients with HFpEF,which were closely related to the cardiac function of patients.Serum WWP1 and NLRP3 have certain diagnostic value for the severity of heart failure in patients with HFpEF.

Role of ovarian tumor stem-like cells sorted from human epithelial ovarian cancer SKOV3 cells in vasculogenic mimicry formation / 南方医科大学学报

OBJECTIVE@#To isolate tumor stem-like cells from human epithelial ovarian cancer SKOV3 cells and explore their role in the formation of vascularization mimicry (VM).@*METHODS@#SKOV3 cells were passaged to the 7th generation by suspension culture in serum-free medium, and the percentages of CD133- and CD117-positive cells in the 1st, 3rd, 5th and 7th generations were analyzed using flow cytometry. The proliferative activity of the cells sorted from the 7th generation SKOV3 cells was assessed with colony formation assay. A three-dimensional cell culture model was established to compare the ability of VM formation between the sorted cells and the parental SKOV3 cells. The expression levels of matrix metalloproteinases-2 (MMP-2) and MMP-9 in the two groups were detected using real-time PCR and Western blotting.@*RESULTS@#Some SKOV3 cells formed typical cell spheres with suspension growth in serum-free medium and were passaged to the 7th generation. Flow cytometry revealed that the percentage of CD133-positive cells increased with cell passaging. The cloning efficiency of the sorted cells was significantly higher than that of the parental SKOV3 cells (50.33% 5.33%, < 0.001). The VM formation ability of the sorted cells was stronger than that of the parental SKOV3 cells in the three-dimensional cell culture system. RT-PCR and Western blotting showed that the expression levels of MMP-2 and MMP-9 were significantly higher in the 7th passage cells than in the parental cells ( < 0.05).@*CONCLUSIONS@#The sorted cells from SKOV3 cells cultured in serum-free medium exhibit biological properties of tumor stem cells with strong VM formation ability, suggesting their role in VM formation.

Expression and significance of vasculogenic mimicry in endometrial carcinoma tissues / 中国肿瘤临床

Objective: To investigate the expression of vasculogenic mimicry (VM) in endometrial carcinoma tissues and its rela-tionship with the clinicopathologic features and prognosis of the disease. Methods: A total of 267 paraffin-embedded endometrial carci-noma specimens of patients with complete follow-up data were collected from the Shijiazhuang Bethune International Peace Hospital between January 2005 and June 2014. CD31-PAS dual staining was performed to identify the VM structure. Tissue samples were then divided into VM-positive and VM-negative groups. CD133 expression was detected by immunohistochemical streptavidin peroxidase method. Results: Among the 267 endometrial carcinoma patients, 65 cases (24.3%) were VM positive. VM formation was closely corre-lated with the International Federation of Gynecology and Obstetrics Staging (χ2=9.987, P=0.002), histodifferentiation grade (χ2=11.795, P=0.001), myometrial invasion depth (χ2=5.499, P=0.019), vascular cancer embolus (χ2=22.599, P<0.001), and lymph node me-tastasis (χ2=7.848, P=0.005). Kaplan-Meier survival curve analysis showed that survival time was significantly shorter in the VM-posi-tive group (median survival time was 51 months) than in the VM-negative group (median survival time was 100 months) (χ2=70.973, P<0.001). Moreover, CD133 expression was significantly higher in the VM-positive group [75.4% (49/65)] than in the VM-negative group [58.9% (119/202)] (χ2=5.720, P=0.017). Conclusion: VM is closely correlated with the pathogenesis, development, and malignancy of endometrial carcinoma. Furthermore, VM is one of the important indexes influencing the prognosis of this disease. Therefore, CD133-positive cells may contribute to VM formation.