1.Expression and clinical significance of FoxM1 and Cep55 protein in basal-like breast carcinoma
Qiushuang MA ; Jinku ZHANG ; Bingjuan ZHOU ; Wenming ZHAO ; Yafei ZHAO
Chinese Journal of Postgraduates of Medicine 2013;(20):7-10
Objective To study the expression and clinical significance of FoxM1 and Cep55 protein in basal-like breast carcinoma (BLBC).Methods The expression of FoxM1 and Cep55 protein in 66 cases of BLBC,70 cases of non-BLBC and 66 cases of normal adjacent breast tissue were detected by immunohistochemistry.Their relationship with the clinical pathological factors was analyzed.Results The positive rate of FoxM1 protein in BLBC,non-BLBC and normal adjacent breast tissue was 77.3% (51/66),60.0%(42/70) and 13.6%(9/66),Cep55 protein was 74.2%(49/66),57.1%(40/70) and 16.7%(11/66),respectively.BLBC and non-BLBC tissue were higher than normal adjacent breast tissue,and BLBC tissue was higher than non-BLBC,there was significant difference (P <0.05).In BLBC tissue,the positive expression of FoxM1 and Cep55 protein correlated with lymph nodes metastasis and TNM staging (P <0.05),while did not correlate with age,menopause,tumor size (P > 0.05).There was direct correlation between the positive expression of FoxM1 and Cep55 protein (r =0.259,P < 0.05).Conclusion FoxM1 and Cep55 protein may play an important role in the carcinogenesis and development of BLBC,and both of them have the synergistic effect.
2.Study on the correlation of extracellular matrix metalloproteinase inducer and atherosclerosis in patients with systemic lupus erythematosus
Qiushuang ZHANG ; Xiuqing YAN ; Fengmei GE ; Zhao LI ; Min ZHAO ; Xue WU ; Xuebin WANG
Chinese Journal of Rheumatology 2021;25(4):236-240
Objective:To Studythe extracellular matrix metalloproteinase inducer (CD147) changes in patients with systemic lupus erythematosus (SLE), and to study thecorrelation of CD147 level and athero-sclerosis in SLE.Methods:Eighty patients with SLE in total were divided into intimal thickening group, (24 cases, group A) and normal intimal group (56 cases, group B) according to carotid intimamedia thickness (IMT) checked by carotid ultrasonography. In addition, their age, bodymass index, blood pressure, seral total cholesterol (TC), high density liptein cholestero (HDL-C), low density lipoprotein cholestero (LDL-C), triglyceride (TG), urinary protein quantitative test(24 h), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anticardiolipin antibody, serum creatinine level, course of the disease, and treatment regimens were collected. Thirty-five healthy people were set as the control group (group C). The levels of serum CD147 were measured by enzyme-linked immuno sorbent assay (ELISA) in 3 groups. The correlation between the serum CD147 level of SLE patients and atherosclerosis was analyzed. The statistical analysis was carried out with independent t-test, chi-square test, analysis of variance, Spearman correlation and Logistic regression. Results:① Levels of serum CD147 in group A [ (238±30) pg/ml] were significantly higher than those in group B [(198±30) pg/ml] and group C [(150±26) pg/ml, F=67.908, P<0.01]. ② Body mass index, hypertensive ratio,total blood cholesterol,urine protein quantitative test (24 h), systemic lupus erythematosus disease activity index (SLEDAI), serum CD147 index in group A were significantly higher than those in group B ( P<0.05). ③ In Logistic regression analysis, serum CD147 [ OR (95% CI)=1.039(1.014, 1.065), P<0.05], urine protein quantitative (24 h) [ OR (95% CI)=2.598(1.033, 6.534), P<0.05] were independently relevant factors affecting carotid artery IMT. Conclusion:Serum CD147 is an independent risk factor for carotid intimamedia thickness in SLE patients.
3.Expressions and significances of apoptosis related protein Bcl-2 and Bax in basal-like breast carcinoma
Bingxin ZHANG ; Xia ZHAO ; Xihua JIA ; Xue CHEN ; Hong CHEN ; Qiushuang MA ; Jinku. ZHANG
Journal of International Oncology 2015;(8):569-572
Objective To investigate the expressions and significances of Bcl-2 and Bax in basal-like breast carcinoma (BLBC).Methods The expressions of Bcl-2 and Bax were detected in 43 cases of BLBC, 57 cases of non-BLBC and 60 cases of normal breast tissues by immunohistochemistry,and their relationships with physiological and pathological characteristics of patients were analysized.Results The positive rate of Bcl-2 in BLBC was 69.77%,higher than 43.86% in non-BLBC (χ2 =6.647,P =0.01 0)and 21 .67% in normal breast tissues (χ2 =23.831 ,P =0.001 ).The positive rate of Bax in BLBC was 20.93%,lower than 45.61 % in non-BLBC (χ2 =6.564,P =0.01 0)and 76.67% in normal breast tissues (χ2 =31 .270,P =0.001 ).The expressions of Bcl-2 and Bax were correlated with lymphnode metastasis (χ2 =6.927,P =0.008;χ2 =6.203,P =0.01 3)and pTNMstaging of BLBC (χ2 =6.331 ,P =0.01 2;χ2 =5.972,P =0.01 5).There was negative correlation between the expression of Bcl-2 and Bax in BLBC (r = -0.408,P <0.01 0). Conclusion High expression of Bcl-2 and low expression of Bax interact with each other leading to unbalance of cell deferation and apoptosis,resulting in promoting genesis and progress of BLBC.
4.Association of Fcgamma receptor ⅢB gene polymorphism with susceptibility and clinical phenotypes of systemic lupus erythematosus
Xin DONG ; Xuebin WANG ; Xiuqing YAN ; Fengmei GE ; Zhao LI ; Qiushuang ZHANG ; Min ZHAO
Chinese Journal of Rheumatology 2020;24(1):37-44
Objective:To study the distribution of FC γ receptor ⅢB gene polymorphism in the Han population in the Yellow River Delta, and to explore the correlation between the gene polymorphism of multiple loci and the susceptibility and clinical phenotypes of systemic lupus erythematosus (SLE).Methods:From January 2017 to December 2017, 144 SLE patients in the Affiliated Hospital of Binzhou Medical College of Shandong Province were selected as the experimental group and 150 healthy people as the control group. Whole blood samples, clinical data and laboratory examination test data were collected. Genomic DNA was extracted by single base extension polymerase chain reaction (PCR) technology and single nucleoside was extracted by mass spectrometry. The relationship between the polymorphism of each point of FC γ receptor ⅢB gene and the susceptibility and clinical phenotypes of SLE was analyzed by χ2 test with SPSS 25.0 software. Results:① The frequencies of CT and TT genotype at rs115878669 were 50.7%, 64.0%, 23.6% and 10.0% respectively in the test group and the control group, the difference was statistically significant ( χ2=5.3, P=0.021; χ2=9.8, P=0.002); The frequencies of TT genotype at rs147574249 were 17.4% and 8.0% respectively in the test group and the control group, the difference was statistically significant ( χ2=5.9, P=0.016); The frequencies of GG and GA genotype at rs199705513 were 20.8%, 10.0%, 59.0%, 70.0%, the difference was statistically significant ( χ2=6.7, P=0.010; χ2=3.9, P=0.049); The frequency of CA genotype at rs77717968 was 30.6% and 46.0% in the test group and the control group, respectively, the difference was statistically significant ( χ2=7.4, P=0.007). ② In the experimental group, the frequencies of heterozygous CT genotypes at rs115878669 were 37.2% and 56.4% in the blood system affected group and the unaffected group, respectively, the difference was statistically significant ( χ2=4.5, P=0.035). In the thrombocytopenia group and the normal platelet normal count group, the frequencies of AG genotypes at rs114531649 were 79.2% and 50.0%, respectively, the difference was statistically significant ( χ2=6.8, P=0.009) and GG genotypes were 4.2% and 25.8%. The difference was statistically significant ( χ2=4.3, P=0.039). The frequency of CC genotype at rs147574249 was 4.2%, 25.8% respectively. The difference was statistically significant ( χ2=5.4, P=0.020). The frequency of CT genotype was 79.2%, 56.7% respectively. The difference was statistically significant ( χ2=4.2, P=0.040). The frequency of CT geno-type at rs115878669 was 70.8%, 46.7%, respectively. The difference was statistically significant ( χ2=4.7, P=0.031). The frequency of AA genotype at rs199705513 was 4.2%, and 23.3%, the difference was statistically significant ( χ2=4.6, P=0.033), the frequency of AA genotype at rs77717968 was 4.2%, 26.7%, and the difference was statistically significant ( χ2= 4.5, P=0.033), the frequency of TT genotype was 25.0%, 9.2%, the difference was statistically significant ( χ2=4.8, P=0.028). There was no statistical significance difference in other comparisons ( P>0.05). The GG genotype frequencies of rs114531649 and the CC genotype frequencies of rs147574249 were 31.2% and 15.7%, respectively. The differences were statistically significant ( χ2=4.9, P=0.027). The AA geno- type frequencies of rs199705513 were 29.5% and 13.2%, the difference was statistically significant ( χ2=5.8, P=0.016), the CC genotype frequency of homozygote at rs61803007 was 32.8%, 16.9%, the difference was statistically significant ( χ2=4.9, P=0.026), the TC genotype frequency of heterozygote was 67.2%, 83.1%, the difference was statistically significant ( χ2=4.9, P=0.026), the AA genotype frequency of homozygote at rs77717968 was 31.2%, 16.9%, respectively, the difference was statistically significant ( χ2=4.1, P=0.044), and there was no significant difference in other comparisons ( P>0.05). The frequency of TC genotype in rs146653557 was 39.4% in serositis group and 75.0% in non serositis group, the difference was statistically significant ( χ2=4.3, P=0.037), the other differences were not statistically significant ( P>0.05). The frequency of CG genotype in rs428194 group and rs61803004 group was 53.8% and 22.9% respectively, the difference was statistically significant ( χ2=12.7, P=0.000 4). The frequency of GG genotype in rs428194 group was 46.2% and 77.1%, 46.2% and 78.1% in rs61803004 group respectively, the difference was statistically significant ( χ2=12.7, P=0.000 4; χ2=13.7, P=0.000 2). The frequencies of GT genotype were 46.2% and 21.0%. The differences were statistically significant ( χ2=9.0, P=0.002 7). The frequency of TT genotypes was 7.7% and 1.0%, the difference was statistically significant ( χ2=4.8, P=0.029). The frequencies of CT genotypes at rs61803008 were 46.2% and 23.8% respectively, the difference was statistically significant ( χ2=6.8, P=0.009 2). The frequencies of TT genotypes were 46.2% and 74.3%. The difference was statistically significant ( χ2=10.1, P=0.001 5). Conclusion:There is a significant correlation between Fc gamma receptor ⅢB gene related loci and SLE susceptibility and clinical phenotypes.
5.Study on the correlation of integr in associated protein and disease activity and bone destruction in patients with rheumatoid arthritis
Xue WU ; Fang SHI ; Xiuqing YAN ; Fengmei GE ; Zhao LI ; Qiushuang ZHANG ; Qu CHEN ; Qi CHEN ; Xuebin WANG
Chinese Journal of Rheumatology 2022;26(9):603-607
Objective:To analyze the serum levels of integrin-associated proteins (CD47) in patients with rheumatoid arthritis (RA), and to explore its association with disease activity and bone destruction in RA.Methods:Serum and clinical data were collected from 65 RA patients and 25 healthy subjects. RA patients were grouped into low, moderate, and high bone erosion groups according to 7-joint ultrasonography score (US7). The levels of serum CD47, thrombospondin-1 (TSP-1) and receptor activator of nuclear factor-κB ligand (RANKL) were measured by enzyme-linked immunosorbnent assay (ELISA) in patients with RA and healthy subjects. The statistical analysis was carried out with independent t-test, analysis of variance, nonparametric rank sum test, pearson or Spearman correlation and logistic regression. Results:① The Serum levels of CD47, TSP-1, and RANKL were higher in the RA group than in the healthy controls ( P<0.01). ② In RA patients, serum CD47 level was positively correlated with disease course ( r=0.301, P<0.05), C-reactionprotein (CRP)( r=0.316, P<0.05), number of tender joints (TJC) ( r=0.254, P<0.05), number of swollen joints (SJC) ( r=0.316, P<0.05), disease activity score in 28 joints (DAS28) ( r=0.255, P<0.05), RANKL ( r=0.252, P<0.05) and TSP-1 ( r=0.260, P<0.05). Serum TSP-1 level was positively correlated with CRP ( r=0.299, P<0.05), TJC ( r=0.335, P<0.01), DAS28 ( r=0.315, P<0.05), RANKL ( r=0.305, P<0.05). ③ The disease course [ OR(95% CI)=1.048(1.033, 1.017)] and TSP-1 [ OR(95% CI)=1.013(1.000, 1.026)] were independently relevant factors affecting bone destruction. Conclusion:CD47 levels is significantly higher in RA patients than in healthy controls, and is associated with disease activity and bone destruction. CD47 may be involved in the bone destruction process of RA by acting on TSP-1.
6.Expressions of cyclin D2 and bcl-2 in diffuse large B-cell lymphoma and their clinical significances
Qiushuang MA ; Ling LI ; Yafei ZHAO ; Jirui SUN ; Bingjuan ZHOU ; Huijuan GENG ; Jinku ZHANG
Journal of Leukemia & Lymphoma 2021;30(7):407-410
Objective:To investigate the expressions and significance of cyclin D2 and bcl-2 in diffuse large B-cell lymphoma (DLBCL) and their clinical significances.Methods:The tissues of 87 DLBCL patients undergoing resection and 23 patients with lymphoid tissue reactive hyperplasia (RLH) in the First Central Hospital of Baoding from January 2015 to March 2020 were collected. Immunohistochemistry method was used to detect the expressions of cyclin D2 and bcl-2 in tissues of DLBCL and RLH, and the relationship between the expressions of cyclin D2 and bcl-2 as well as the association with the clinicopathological features of DLBCL patients.Results:The positive rates of cyclin D2 protein in DLBCL and RLH were 33.3% (29/87) and 2.0% (1/23), the positive rates of bcl-2 protein in DLBCL and RLH were 60.9% (54/87) and 7.0% (3/23); the positive rates of cyclin D2 and bcl-2 in DLBCL were higher than those in RLH, and the differences were statistically significant( χ2=7.566, P=0.006; χ2=17.512, P < 0.01). The expressions of cyclin D2 and bcl-2 proteins were related to the Ann Arbor staging and immunophenotype of DLBCL patients (all P < 0.05), while not related to age, gender, cancer location, tissue type (all P > 0.05). There was a positive correlation between the expressions of cyclin D2 and bcl-2 protein in DLBCL ( r=1.000, P < 0.01). Conclusions:cyclin D2 and bcl-2 may be related to the development and progression of DLBCL, and both may have some synergies.
7.Dosimetry advantage of respiratory gating in the treatment of hepatocellular carcinoma with large segmentation
Ziyin CHEN ; Yanchun BAI ; Yangsen CAO ; Jian LI ; Lili XU ; Qiushuang ZHAO ; Yang WANG
Practical Oncology Journal 2019;33(6):536-539
Objective The aim of this study was to investigate the dosimetric advantages of Gating in the treatment of prima-ry hepatic cancer with large segmentation. Methods A retrospective analysis of 10 patients with primary liver cancer from August 2017 to November 2018 after interventional therapy was performed using three consecutive phases of end-tidal phase to achieve pa-tient-controlled large-segment radiotherapy. Ten patients underwent 4DCT localization scan,and 10 respiratory phase sequences were reconstructed by respiratory wave-form,and the images were transmitted to the MIM6. 7. 6 workstation. In the MIM workstation, full-time phase maximum density projection(MIP-10),full-time phase average density projection(Mean-10),end-expiration 3 phase maximum density projection(MIP-3) and end-expiration 3 phase average density projection( Mean-3) were generated re-spectively,where MIP was used for target delineation and Mean for dose calculation. The radiotherapy doctor delineated IGTV-10 and IGTV-3 on the MIM workstation,and released CTV-10,CTV-3,PTV-10 and PTV-3 to compare the volume differences of the target area. After the target area was drawn,the image was transmitted from the MIM workstation to the Eclipse treatment planning sys-tem,and the full-time phase plan(Plan-10)with the same conditions and three consecutive phase-phase gating plans(Plan-3) were prepared. The prescriptive dosage was given at 50 Gy/10 f/2weeks. Comparing the HI and CI of the target area,the comparison of organs at risk included: the average dose of liver Dmean,the irradiation volume of liver less than 15Gy,the Dmax of small intestine, the Dmax of colon, the Dmax of stomach, the average dose of the kidney Dmean, the heart Dmax, and the spinal cord Dmax. Results The volume of the target area delineated at the end of expiratory phase was less than that of the target area outlined by the full-time phase in IGTV,CTV and PTV,and the difference was statistically significant(P<0. 05). In the two groups of seven field coplanar lage-segment radiotherapy plans,the 3-phase respiratory gating plan significantly reduced the dose of the organs at risk, and the difference was statistically significant(P<0. 05). At the same time,there was no statistically difference in the HI and CI be-tween of the two groups(P>0. 05). Conclusion The gated target area delineation and planning design of the three consecutive pha-ses of end-tidal phase reduce the volume of IGTV,CTV and PTV target regions compared with the selection of full-time phase,and have obvious advantages in the planned dosimetry. The irradiation dose that threatens the organs is worthy of being promoted and ap-plied in the large-scale radiotherapy of liver cancer.
8.The role of tofacitinib in early atherosclerosis in mice with systemic lupus erythematosus
Qu CHEN ; Fengmei GE ; Zhao LI ; Qiushuang ZHANG ; Xue WU ; Qi CHEN ; Saiqi LI ; Xuebin WANG ; Xiuqing YAN
Chinese Journal of Rheumatology 2024;28(2):106-112
Objective:To investigate the effect of tofacitinib on early atherosclerosis of patients with systemic lupus erythematosus and explore the possible relationship between lupus nephritis and early atherosclerosis of systemic lupus erythematosus.Methods:Sixteen 8-week-old female MRL/lpr mice with a body weight of 20~25 g were selected and randomly divided into the treatment group and placebo group, with 8 mice in each group. The treatment group diluted tofacitinib by normal saline, and given at a dose of 10 mg·kg -1·d -1, and the placebo group (starch tablets) administered the medication in the same way as the treatment group for a total of 8 weeks. The ELISA method was applied to detect serum anti-dsDNA antibody levels in the two groups of mice. Bradford method protein concentration was used to determine the level of urine protein in mice. Automatic biochemical analyzer was used to detect blood lipids, urea nitrogen, serum creatinine, complement C3, complement C4 levels. Western blotting was used to determine the protein expression levels of monocyte chemoattractant protein-1 (MCP-1), non-receptor protein tyrosine kinase family 1 (JAK1), signal transducer and activator of transcription 1 (STAT1) and signal transducer and activator of transcription 2 (STAT2) in aortic and kidney tissues. After the aortic arch section were prepared, oil red O was used to stain the sections, and the vascular plaque area and intimal thickness were evaluated by ImageJ software. The kidneys were dissected and stained with HE, and the active lesions of lupus nephritis were evaluated using the glomerular activity scoring system. SPSS 23.0 software was used for statistical analysis, in which the between-group comparison was performed using two independent samples t-test, and the correlation analysis was performed using the Spearman method. Results:①The serum anti-dsDNA antibody expression level in the treatment group [(5.2±1.0) U/ml] was lower than that in the placebo group [(6.9±1.2) U/ml], ( Z=-3.07, P=0.008), and the levels of complement C3 and complement C4 were higher than those in the placebo group [(293±10) mg/L vs. (260±19) mg/L, Z=2.72, P=0.017]; (16±6) mg/L vs. (8±9) mg/L, Z=3.78, P=0.006]. There was no significant difference in serum BUN and Scr between the treatment group and the placebo group [(10.6±0.7) mmol/L vs. (11.5±1.1) mmol/L, Z=-1.96, P=0.071; (17±5) μmol/L vs. (22±6) μmol/L, Z=-1.79, P=0.095]. ② Compared with the placebo group, the levels of LDL, TC and TG in the treatment group decreased [(0.83±0.15) mmol/L vs. (1.08±1.05) mmol/L, Z=-3.95, P=0.001; (2.90±0.08) mmol/L vs. (1.81±0.97) mmol/L, Z=-5.17, P=0.001; (1.10±0.08) mmol/L vs. (1.60±0.42) mmol/L, Z=-3.23, P=0.013], and HDL level increased [(2.02±0.99) mmol/L vs. (1.81±0.97) mmol/L, Z=4.42, P=0.001]. ③ Compared with the placebo group, the levels of aortic MCP-1, JAK1, STAT1 and STAT2 in the treatment group were reduced [(0.17±0.30) vs. (0.23±0.05), Z=-3.06, P=0.009; (0.83±0.09) vs. (1.05±0.19), Z=-3.07, P=0.008; (0.77±0.07) vs. (0.94±0.13), Z=-2.83, P=0.014; (0.70±0.07) vs. (0.82±0.09), Z=-2.83, P=0.013], the aortic plaque area and aortic intimal thickness were lower than those in the placebo group [(12±31) μm 2vs. (1 242±1 101) μm 2, Z=-3.12, P=0.016; (63±7) μm vs. (82.10±8.06) μm, Z=-5.13, P<0.001]. ④ Compared with the placebo group, the urine protein level and glomerulonephritis activity score in the treatment group were decreased [(0.08±0.03) mg/mL vs. (0.20±0.11) mg/mL, Z=-3.08, P=0.015; (1.79±0.38) vs. (2.79±0.14) points, Z=-7.08, P<0.001)], and renal tissue MCP-1, JAK1, STAT1.Compared with the placebo group, STAT2 levels were reduced [(0.364±0.040) vs. (0.425±0.021), Z=-3.85, P=0.003; (0.689±0.074) vs. (0.838±0.068), Z=-4.19, P=0.001; (0.508±0.070) vs. (0.646±0.019), Z=-2.85, P=0.015; (0.618±0.062) vs. (0.740±0.101), Z=-2.94, P=0.013. ⑤ The glomerular mobility scores of the two groups were positively correlated with LDL, TCHO, TG, aortic plaque area and aortic intimal thickness ( r=0.51, P=0.043; r=0.79, P<0.001; r=0.64, P=0.008; r=0.82, P<0.001; r=0.74, P=0.001), and negatively correlated with HDL ( r=-0.53, P=0.036). The urine protein levels in the two groups were positively correlated with LDL, TC, TG, aortic plaque area and aortic intimal thickness ( r=0.67, P=0.004; r=0.68, P=0.004; r=0.53, P=0.033; r=0.80, P<0.001; r=0.74, P=0.001), and negatively correlated with HDL ( r=-0.57, P=0.021). Conclusion:The severity of lupus nephritis is correlated with atherosclerosis and dyslipidemia in the early stage of systemic lupus erythematosus. Tofacitinib may reduce the degree of early arteriosclerosis and lupus nephritis in MRL/LPR mice, and reduce blood lipid levels, which may be effective in improving the prognosis of SLE and improving the survival rate of patients.