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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.
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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.
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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.
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Objective To explore the level of serum hypoxia-inducible factor (HIF)-1α and the effect of pantoprazole on HIF-1α in patients with gouty arthritis.Methods Subjects were divided into acute gouty arthritis (group A),intermittent gouty arthritis (group B) and healthy controls (group C).Patients in group A were divided into mild (A1) and severe (A2) subgroups according to the severity of inflammation.Levels of serum HIF-1α in the three groups,and the levels of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in group A1 and group A2 were detected by enzyme-linked immunosorbent assay (ELISA).Patients in group A2 were randomly divided into three groups,saline 100 ml/twice a day,20％ pantoprazole 100 ml,twice a day and 40％ panto-prazole 100 ml,twice a day were administered respectively.After 7 days,the levels of serum HIF-1α were measured by ELISA.One-way analysis of variance (ANOVA) and two independent sample t test were conducted in this study.Results ① Levels of serum HIF-1α in group A [(48±13) ng/L] were significantly higher than those in group B [(40±12) ng/L,P＜0.01] and group C [(28±12) ng/L,F=29.838,P＜0.01].② Levels of serum HIF-1α [(56±10) ng/L],IL-1β [(51 ±13) ng/L] and TNF-α [(161 ±45) ng/L] in the experimental group A2 were higher than those in the experimental group A1 [HIF-1α:(42±11) ng/L,t=4.600,P＜0.01;IL-1β:(42±12) ng/L,t=2.552,P＜0.05;TNF-α:(122±34) ng/L,t=3.432,P＜0.01].③ Levels of HIF-1α [(26±6) ng/L],IL-1β [(23±4) ng/L],TNF-α [(92±6) ng/L] in the 40％ pantoprazole group were lower than those in 20％ pantoprazole 100 ml,twice a day group [HIF-1α:(33±4) ng/L];IL-1β:(30±5) ng/L;TNF-α:(102±7) ng/ L] and saline group [HIF-1α:(37±5) ng/L];IL-1β:(38±5) ng/L];TNF-α:(108±9) ng/L](all P＜0.05);Levels of HIF-1α,IL-1β and TNF-αin the 20％ pantoprazole group were lower than those in saline group (all P＜0.05).Conclusion ① HIF-1α may be one of the indicators of acute inflammation,which may reflect the degree of inflammation in patients with gout.② Pantoprazole can reduce the level of serum HIF-1α,IL-1β and TNF-α in patients with gouty arthritis,with a concentration dependent characterisit.
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Objective To investigate whether B-cell activating factor (BAFF) involved in the patho-genesis of lupus nephritis (LN) by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling. Methods Twenty-eight lupus nephritis patients and 20 controls were included in this study. The clinical data were collected. BAFF levels in plasma were measured by ELISA, and the relationship between systemic lupus erythematosus disease activity index (SLEDAI) and BAFF were analyzed. The mRNA and protein levels of BAFF, phosphorylated-PI3K (p-PI3K), phosphorylated-Akt (p-Akt), phosphorylated-mTOR (p-mTOR) and Bcl-2 in kidney tissues were measured using real-time polymerase chain reaction (RT-PCR) and Western blotting. Data were analyzed using Mann-Whitney U test and Spearman correlation analysis. Results ①Plasma BAFF levels were significantly higher in LN patients [(580 ±45) ng/L] compared with controls [(208 ±30) ng/L](Z=-5.856, P<0.01), and significant positive correlation was found between plasma BAFF levels with SLEDAI (r=0.723, P<0.01). ② Plasma BAFF level in LN patients was positively correlated with 24 h UP and anti-dsDNA titers (r=0.381, 0.461, P<0.05). The protein level of BAFF in kidney tissues was positively correlated with 24 h UP and anti-dsDNA titer (r=0.469, 0.489, P<0.05).③The mRNA levels of BAFF, p-PI3K, p-Akt, p-mTOR and Bcl-2 in kidney tissues were increased in patients compared to controls[5.8±1.8 vs 2.1±0.7, Z=-4.915, P<0.01;6.7±0.9 vs 1.71±0.53, Z=-5.857, P<0.01;5.6±0.9 vs 1.8 ±0.5, Z=-5.751, P<0.01; 5.6 ±1.4 vs 1.6 ±0.4, Z=-5.291, P<0.01; 2.11 ±0.36 vs 1.33 ±0.22, Z=-4.844, P<0.01].④The protein levels of BAFF, p-PI3K, p-Akt, p-mTOR and Bcl-2 in kidney tissues were increased in patients compared to controls [0.72±0.19 vs 0.31±0.05, Z=-4.747, P<0.01;0.73±0.11 vs 0.33±0.09, Z=-5.834, P<0.01;0.77±0.06 vs 0.22±0.07, Z=-5.855, P<0.01;1.18±0.27 vs 0.47±0.13, Z=-5.416, P<0.01;2.08±0.37 vs 1.32±0.18, Z=-4.998, P<0.01]. Conclusion The findings of this study indicate that BAFF may participate in the pathogenesis of LN by regulating PI3K/Akt/mTOR signaling.
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Objective To explore the circadian rhythm of interleukin (IL)-6 in collagen induced arthritis (CIA) rats and investigate the effectiveness and safety of methotrexate (MTX) administered according to IL-6 rhythm.Methods Serum IL-6 concentrations of CIA and normal rats at different time points were measured by enzyme-linked immunosorbent assay (ELISA).CIA rats were randomly divided into the experimental group A,experimental group B and control group.MTX (1/7 mg·kg-1 ·d-1) was administered once a day when the IL-6 level began to increase or decrease in the experimental group,while MTX (1 mg/kg) administered once a week in the control group.Arthritis scores and leukocyte counts were observed.The production of IL-6 and C reactive protein (CRP) levels in the serum were measured.Moreover,histological changes in the ankle joint were examined.One-way analysis of variance (ANOVA),two independent sample t test were used to evaluate the experimental data.Results The plasma IL-6 levels in CIA rats were different at different time points,which began to increase at 18:00 and decrease at 6:00.Arthritis score in the experimental group A (4.8±0.7)was lower than that in the control group (5.8±1.0,t=2.256,P=0.0406) and experimental group B (5.5±0.5,t=2.393,P=0.0313).The levels of TNF-α [(185±21) ng/L],IL-6 [(99±6) ng/L],IL-1β[(20.1±1.6) ng/L] and CRP[(1251±282) μg/L] in the experimental group A were significantly lower than those in control group [TNF-α:(207±10) ng/L,t=2.726,P=0.016 4;IL-6:(100±6) ng/L,t=2.669,P=0.0183;IL-1β:(22.0±1.3) ng/L,t=2.814,P=0.0138;CRP:(1 417±278) μg/L,t=2.369,P=0.0327].The level of IL-6 in the experimental group A[(93±6) ng/L] was lower than that in the experimental group B [(99±6) ng/L,t=2.323,P=0.0358].Compared with the control group [(9650±1062)/μl],the counts of leukocyte in the experimental group A [(4595±603)/μl,t=3.841,P=0.0064] and experimental group B [(3833±585)/μl,t=4.442,P=0.003] were significantly lower.Compared with the control group (9.1 ±2.0),histopathology scores in the experimental group A (6.6±1.3,t=2.606,P=0.015) and experimental group B (7.4±1.3,t=3.857,P=0.0007) were significantly lower.Conclusion The plasma IL-6 levels in CIA rats have shown evident circadian rhythm.There-fore,once a day administration is better than once a week.The therapeutic effect of RA may be improved by administering MTX at the time points according to the circadian rhythm of IL-6.