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Objective:To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities.Methods:Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups.Results:A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)].Conclusions:The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients′ liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.
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Objective@#To explore the effects of long non-coding RNA (LncRNA) MIR22HG on proliferation,apoptosis and inflammatory response of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) and its molecular mechanism.@*Methods@#Synovial tissue samples were collected from 37 RA patients and 30 joint trauma patients in our hospital,and the expression levels of MIR22HG and miR-22-5p in synovial tissue were detected by qRT-PCR. RA-FLSs in human was isolated ,cultured and identified in vitro. MIR22HG siRNA interference plasmid (si-MIR22HG) and its negative control plasmid (si-NC) ,miR-22-5p inhibitor and its negative control (inhibitorNC) were transfected into RA-FLSs respectively or simultaneously.The expression levels of MIR22HG and miR- 22-5p were detected by qRT-PCR. CCK-8 was used to detect the proliferation activity of cells in various groups. Annexin Ⅴ- FITC / PI was used to detect the apoptosis rates of cells in various groups.ELISA was used to detect the levels of TNF-α , IL-1 β and IL-6 in the supernatant of cells in various groups.Western blot was used to detect the protein expression levels of Bcl-2,Bax and Cleaved caspase-3 of cells in various groups.The targeting relationship between MIR22HG and miR-22-5p was verified by dual luciferase reporter gene assay. @*Results @#Compared with joint trauma patients,the expression level of MIR22HG in synovial tissues of RA patients increased (P<0. 05) , while the expression level of miR-22-5p decreased (P<0. 05) .Interference with MIR22HG inhibited the proliferation activity of RA-FLSs,decreased the levels of TNF-α , IL-1 β and IL-6 in cell supernatant and the protein expression level of Bcl-2 in cells (P<0. 05) ,and increased the apoptosis rate,the expression level of miR-22-5p and the protein expression levels of Bax and Cleaved casepase-3 (P <0. 05 ) .However,inhibition of miR-22-5p expression reversed the effects of MIR22HG gene silencing on proliferation,apoptosis and inflammation of RA-FLSs (P<0. 05) .Dual luciferase reporting assay showed that miR-22-5p was a potential downstream miRNA target of MIR22HG.@*Conclusion@# MIR22HG is highly expressed in synovial tissues of RA patients,and it may promote the proliferation and the inflammatory response of RA-FLSs and inhibit cell apoptosis by down regulating the expression of miR-22-5p.
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Osteoarthritis (OA) is the most common form of arthritis and the leading cause of old age disability, affecting an estimated 302 million people worldwide. OA is seriously overlooked in the world. The awareness of OA and the popularization of standardized diagnosis and treatment are all lacking. Knees, hips, and hands are the most commonly affected joints in OA. Based on the experience of diagnosis and treatment, consensus and guidelines, we formulated this diagnosis and treatment standard in order to standardize the diagnosis and treatment of OA. We hope that our standard can reduce misdiagnosis and mistreatment and improve the prognosis of OA.
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Objective To investigate the serum concentration of soluble klotho (s-kl) in systemic lupus erythematosus (SLE) and lupus nephritis (LN) ,and elucidate its role in SLE and LN .Methods A total of 34 patients ,definitely diagnosis as SLE with un-treatment firstly ,were enrolled in this study .The patient were divided into two groups ,those who complicated with LN were assigned to LN group (15 cases) ,the others were distributed to SLE group (19 cases) .At the same time ,17 cases of routine physical examination people were take as control group .24 hours urine of all the cases was collected for examining urinary protein (Upro) .Routine hemocyte analysis ,serum biochemical parameters and ANA and dsDNA were measured by routine method .ELISA was used to detect s-kl ,25-hydroxy vitamin D (25-OH-D) and fibroblast grow th factor-23 (FGF-23) .Systemic lupus erythematosus disease activity index (SLEDAI) was performed in SLE and LN group ,and the creatinine clearance rate(CCr)was calculated accord-ing to the Cockcroft-Gault formula .Pearson′s and linear regression were applied to analyisis the correlation of relevant parameters . Results As compared with the control group ,there were statistically significant differences in mean arterial pressure ,blood rou-tine ,creatine kinase (CK) and lactate dehydrogenase (LDH ) ,complement (C3 and C4 ) and dsDNA in SLE and LN group (P 0 .05) ,but the serum level of s-kl ,25-OH-D and FGF-23 in LN group were showed a statistical significance when compared with SLE or control group(P< 0 .05) .Meanwhile ,the SLEDAI score was higher in LN than in SLE group(P< 0 .05) .Correlation analysis indicted that s-kl exhibited a positive relationship with 25-OH-D ,C3 and C4 ,while showed a negative correlation with FGF-23 ,SLEDAI and dsDNA(all P< 0 .05) .However ,no any corre-lationt was revealed in regression analysis between the s-kl ,25-OH-D ,FGF-23 and the lupus activity .Conclusion The decrease of s-kl maybe one of the pivotal factors that up-regulated the level of FGF-23 in SLE and LN patients ,thus lead to the deficiency of vi-tamin D and lupus activity .
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Objective To determine the role of fosinopril and valsartan intervention in Klotho, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor (PAI-1) gene expression in hypertensive renal interstitial fibrosis (RIF) in the kidney tissue of spontaneously hypertensive rats (SHR). MethodsWe randomly divided 20 male 22-week-old SHR into 4 groups (5 in each group):a hypertension group (SHR group), a fosinopril group [Fos group, 10 mg/( kg·d) gavage], a valsartan group [Val group, 10 mg/( kg·d) gavage], and a fosinopril plus valsartan group [Fos + Val group, fosinopril 10 mg/( kg·d) + valsartan 50 mg/( kg·d) gavage]. Another five 22-week-old male Wistar Kyoto rats (WKY) were used as controls. Through monitoring the weight of the rats, tail artery pressure, 24-hour urine protein by fosinopril and/or valsartan intervention after the 8-week trial. RT-PCR and Western blot were used to detect the mRNA and protein expression of Klotho, MMP-9, TIMP-1, and PAI-1 in the kidneys.Results RT-PCR showed that in the SHR group, Klotho mRNA and protein expression were significantly decreased(P<0.01), while mRNA and protein expression of MMP-9, TIMP-1, and PAI-1 were significantly higher compared with the WKY group(P<0.01). With fosinopril and / or valsartan intervention, Klotho mRNA expression in the Fos group (P<0.01), Fos + Val group (P<0.01), Val group (P<0.05), Klotho protein expression in the Fos group(P<0.05), Fos + Val group (P<0.05), Val group (P<0.01), were significantly increased compared with those in the SHR group. The mRNA and protein expression of MMP-9, TIMP-1, and PAI-1 in the Fos group, Val group, and Fos + Val group were significantly lower than those in the SHR group (P<0.01). The expression of Klotho mRNA had negative correlation with the expression of MMP-9 mRNA (r= -0.864, P<0.01), TIMP-1 mRNA (r=-0.725, P<0.01) and PAI-1 mRNA (r=-0.785, P<0.01). The Klotho protein expression had negative correlation with the expression of MMP-9 protein (r=-0.614, P<0.05), TIMP-1 protein (r=-0.579, P<0.05), and PAI-1 protein (r=-0.552, P<0.05). Conclusion Anti-aging gene Klotho and the genes related with extracellular matrix degradation gene MMP-9, TIMP-1, PAI-1 are involved in hypertensive renal injury. The expression of Klotho and MMP-9, TIMP-1, and PAI-1 is closely correlated. Fosinopril and valsartan which increase the Klotho mRNA and protein expression can alter the expression of Klotho-MMPs/TIMPs, which may be the main mechanism to prevent interstitial fibrosis.
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Objective To observe the effect of Cordceps Sinensis (CS) on the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the kidney of spontaneously hypertensive rats(SHR), and to investigate the mechanism of CS. Methods Male SHRs (23 week old) were randomly divided into 4 groups: a group without any treatment (Group S), a group treated with Cordceps sinensis at 4 F), and a group received daily intragastric administration of CS at 4 male WKY rats were used as normals controls. At the end of 8 weeks, all rats were sacrificed. Serum creatinine(Scr), 24 h urinary protein count, and the expression of ICAM-1 and VCAM-1 were examined by immunohistochemical technique and RT-PCR. Results Compared with the WKY rats, blood pressure, 24 h urinary protein count, Scr,and the expression of ICAM-1 andVCAM-1 in the kidney of SHR significantly increased (P<0.05).Compared with Group S, blood pressure decreased after treatment by fosinopril (P<0.05). Compared with Group S, the levels of Scr, 24 h urinary protein count, and glomerular lesion were significantly reduced in the CS and/or fosinopril treatment group. The expression of ICAM-1 and VCAM-1 was significantly decreased in these groups (P<0.05).Conclusion CS may play a role in the protection and anti-fibrosis in the process of renal injury in SHR through reducing the expression of ICAM-1 and VCAM-1.