1.Expression and clinical significance of long non-coding RNA differentially expressed genes, micro RNA-181a-5p and autophagy-related protein 5 in primary gouty arthritis
Jianwei GUO ; Tianyi LEI ; Peng WANG ; Zeng ZHANG ; Guilin JIAN ; Quanbo ZHANG ; Yufeng QING
Chinese Journal of Rheumatology 2024;28(5):303-311
Objective:To explore the expression and clinical significance of long non-coding RNA colorectal neoplasia differentially expressed (lncRNA CRNDE), microRNA-181a-5p (miR-181a-5p) and autophagy related 5 (ATG5) in the peripheral blood of patients with gouty arthritis (GA) patients.Methods:The clinical data, laboratory parameters and peripheral blood samples were collected from 40 patients with acute gout (AG), 40 patients with intermittent gout (IG) and 50 healthy subjects (HC). The expression levels of lncRNA CRNDE, miR-181a-5p and ATG5 mRNA were detected by real-time fluorescence quantification (RT-qPCR) and the expression level of ATG5 protein was detected by Western-blot. The expression levels of lncRNA CRNDE, miR-181a-5p, ATG5 mRNA were compared among the three groups and correlated with clinical indices, and a subject operating characteristic curve (ROC) was constructed to assess the value of lncRNA CRNDE, miR-181a-5p, ATG5 mRNA in the diagnosis of gout. Measurements conforming to normal distribution were analyzed using t test or ANOVA, data with non-normal distribution was analyzed using Mann-Whitney U test or Kruskal-Wallis H test, correlation analysis between variables was analyzed using Spearman's analysis, and the diagnostic value of each indicator was analyzed using ROC curve. Results:① The differences in the expression of lncRNA CRNDE, miR-181a-5p, and ATG5 mRNA between the three groups were statistically significant ( H=32.12, 57.73, 68.32, all P<0.001). Among them, lncRNA CRNDE expression level in the AG group was significantly higher than that in the IG group and healthy control group [61.95(11.39, 108.30)×10 -3, 25.71(15.40, 38.40)×10 -3, 13.80(3.97, 23.99)×10 -3; Z=-3.24, P=0.001; Z=-5.03, P<0.001], and the expression level of IG group was higher than that of healthy control group( Z=-3.56, P<0.001); miR-181a-5p and ATG5 mRNA expression levels in AG group were significantly lower than those in IG group and healthy control group [miR-181a-5p: 39.81(31.22, 69.38)×10 -3, 60.74(44.19, 90.35)×10 -3, 121.30(101.50, 316.90)×10 -3; Z=-3.01, P=0.030; Z=-6.93, P<0.001. ATG5 mRNA: 4.52(2.31, 26.63)×10 -3, 43.63(13.72, 102.70)×10 -3, 153.90(66.62, 365.80)×10 -3; Z=-5.47, -7.36, all P<0.001)], which were expressed at lower levels in the IG group than in the healthy controls ( Z=-5.25, -4.47, all P<0.001). The difference of ATG5 protein expression level among the three groups expressed was statistically significant ( F=6.24, P=0.030), and the AG group was higher than the healthy control group, and the difference was statistically significant [(0.96±0.13) vs.(0.61±0.04), t=4.25, P=0.013], but the difference between the IG group (0.78±0.15) and the AG group and the HC group was not statistically significant ( t=1.51, P=0.206; t=1.85, P=0138). ② Spearman correlation analysis showed that lncRNA CRNDE was negatively correlated with the expression levels of miR-181a-5p and ATG5 mRNA in gout patients ( r=-0.49, P<0.001; r=-0.35, P=0.002); miR-181a-5p was positively correlated with ATG5 mRNA expression levels ( r=0.64, P<0.001); lncRNA CRNDE expression level was positively correlated with ESR and WBC ( r=0.49, P<0.001; r=0.43, P=0.001); miR-181a-5p expression level was negatively correlated with ESR and WBC ( r=-0.29, P=0.009; r=-0.35, P=0.002), and ATG5 mRNA expression levels were negatively correlated with ESR, WBC, and GR ( r=-0.26, P=0.021; r=-0.26, P=0.024; r=-0.27, P=0.021). In the AG group lncRNA CRNDE was positively correlated with ESR and WBC ( r=0.36, P=0.022; r=0.36, P=0.026) and miR-181a-5p was negatively correlated with WBC ( r=-0.34, P=0.038) ③ ROC curve showed that the areas under ROC curve of lncRNA CRNDE, miR-181a-5p and ATG5 mRNA expression levels to predict gout were 0.764, 0.875 and 0.864, respectively. The area under ROC curve of gout predicted by the three combined was 0.928. Conclusion:lncRNA CRNDE, miR-181a-5p, and ATG5 may be involved in the pathoge-nesis of primary gouty arthritis, and are potential biological parameters for studying the pathogenesis of gout.
2.The prevalence and related risk factors of hyperuricemia in Bozidum Kinghiz township of Xinjiang Aksu region
Yan ZHONG ; Nasha GU ; Zhengfang LI ; Xue WU ; Mansuer MIKELAYI· ; Yamei SHI ; Cainan LUO ; Xiaomei CHEN ; Qianqian WANG ; Chaohong YUE ; Yun FENG ; Xinyan MENG ; Guoli ZHANG ; Juan DENG ; Jing LI ; Lijun WU
Chinese Journal of Rheumatology 2024;28(5):312-320
Objective:To investigate the prevalence of hyperuricemia (HUA) in Bozidun Kirghiz township of Xinjiang Aksu region, and to explore the risk factors for the occurrence of HUA in the local area.Methods:A cross-sectional survey study was conducted by randomly selecting 9 villages in Bozidun Kirgiz Township by the whole-group sampling method and questionnaire were distributed to the households. The questionnaire included: demographic information, history of past illness, personal history, and all subjects were measured for height, weight, blood pressure, abdominal circumference, etc. The diagnostic of HUA if the serum uric acid (SUA) level >420 μmol/L in men or >360 μmol/L in women. The incidences of HUA in different age, sex, food type and life style behavior were analyzed. T test, non-parametric test and Chi-square test were used to analyze the differences among the groups, and logistic regression was used to analyze the risk factors. Results:①A total of 2 138 subjects were surveyed, among which 68 patients were with HUA, the prevalence of HUA in Bozidun Kirghiz township, Aksu region in the general population was 3.18%(68/2 138); the prevalence rate in men was 4.60%(45/978), 45 patients were identified; and the prevalence rate in women was 1.98%(23/1 160), 23 patients were identified. The peak age of HUA in male and female patients was 51~60 years old. ②The prevalence of HUA was lower in those who consumed dairy products ( χ2=6.91, P=0.017), nuts ( χ2=8.43, P=0.038) and eggs ( χ2=7.38, P=0.023), and lower in those who consumed more. Different intake of cereals ( χ2=0.87, P=0.647), meat( χ2=0.82, P=0.662), vegetables and fruits( χ2=5.22, P=0.073) had no effect on the prevalence of HUA.③In terms of different life behaviors, the prevalence of HUA in men who had been smoking was higher than those who had never smoked (57.78%, 28.89%, 13.33%, χ2=8.16, P=0.017). In the relationship between drinking and HUA, the prevalence rates of male always drinking, ever drinking and never drinking were 80.00%, 11.11% and 3.89%, respectively, the difference was statistically significant ( χ2=6.67, P=0.038). ④Multi-factor logistic regression analysis showed that high BMI, old age, high TG, increased Cr and increased WBC were risk factors for the occurrence of HUA [ OR(95% CI)=1.13(1.04, 1.23), 1.03(1.00,1.05),1.39(1.00, 1.93), 1.03(1.02, 1.05), 1.27(1.07, 1.49), all P<0.05]. Conclusion:The prevalence of HUA in Bozidun Kirgiz township in Aksu prefecture of Xinjiang is lower than that in other areas with continental climate. High BMI, old age, high TG, increased Cr and increased WBC count are risk factors for the development of HUA .
3.Safety of tocilizumab combined with traditional antirheumatic drugs in the treatment of systemic juve-nile idiopathic arthritis
Mengmeng WANG ; Zhidan FAN ; Lingzhi QIU ; Yong ZHANG ; Wenjing LI ; Haiguo YU
Chinese Journal of Rheumatology 2024;28(5):321-326
Objective:To investigate the safety of tocilizumab (TCZ) in the treatment of children with systemic juvenile idiopathic arthritis (sJIA).Methods:Data of children aged 2 to 18 years with the diagnosis of sJIA and treated with TCZ from June 1, 2017 to June 30, 2022 at our hospital were retrospectively collected. The clinical medication characteristics, incidence, severity and outcome of adverse drug reactions (ADR) were statistically analyzed. Univariate and multivariate analysis were used to analyze the risk factors of TCZ-induced ADR. Univariate comparison between groups were compared to the measured data followed by t test for normal distribution, and the counting data were paired with Chi-square test. Binary logistic regression analysis was used for multivariate analysis. Results:A total of 83 eligible children were enrolled. The age at TCZ initiation was (8.5±3.7) years old. Most of the children received oral glucocorticoid (86.8%) and/or methotrexate (72.3%) prior to TCZ treatment. The mean time of TCZ duration was (1.2±0.9) years, the total TCZ exposure was 92.70 patient years. Fifty-five (66.3%) children reported 123 ADR, with a rate of 132.69/100 patient years. Forty-two (50.6%) children reported 103 general ADR, with a rate of 111.11/100 patient years. Eighteen (21.7%) children reported 20 serious ADR, with a rate of 21.57/100 patient years. The results of univariate analysis showed that the dosage of glucocorticoid in ADR group was higher than that in non-ADR group [(0.76±0.50) mg·kg -1·d -1vs. (0.52±0.41) mg·kg -1·d -1, t=2.27, P=0.026], and the difference was statistically significant. However, there were no significant differences in gender [(male 23, female 32) cases vs. (male 9, female 19) cases, χ2=0.73, P=0.392], age at TCZ initiation [(8.5±3.8) years old vs. (9.0±3.1) years old, t=-0.65, P=0.516], duration of TCZ treatment [(1.24±1.00) years vs. (1.05±0.90) years, t=0.87, P=0.385], methotrexate doses weekly [(8.0±5.2) mg/m 2vs. (7.6±5.1) mg/m 2, t=0.39, P=0.696], and history of drug or food allergy (11 cases vs. 5 cases, χ2=0.06, P=0.815) between the two groups. The results of binary logistic regression analysis showed that the combined use of oral glucocorticoids was an independent risk factor for TCZ-induced ADR [ OR (95% CI) =3.05 (1.11, 8.36), P=0.030]. The risk of ADR was 3.05 times higher in the combined daily dose of glucocorticoids ≥0.76 mg/kg prednisone equivalent than that of < 0.76 mg/kg. Common general ADR to TCZ include infections (38.83/100 patient years) and abnormalities in laboratory parameters (37.76/100 patient years) such as elevated glutamic-pyrupiane transaminase (18.34/100 patient years), dyslipidemia (12.94/100 patient years), and hemocytopenia (5.39/100 patient years). The serious ADR included serious infection (9.71/100 patient years) and serious infusion reaction(7.55/100 patient years). All ADR were improved after drug withdrawal or symptomatic treatment, and no deaths occurred. Conclusion:TCZ has a good safety profile in the treatment of sJIA. Serious infections and severe infusion reactions often lead to discontinuation of the drug. The combination of glucocorticoids≥0.76 mg/kg prednisone equivalent is an independent risk factor for TCZ-induced ADR. Monitoring should be strengthened during the application of TCZ, and ADR should be detected and treated as early as possible to reduce the risk of medication related adverse reactions.
4.The effectiveness and safety of mesenchymal stem cells in the treatment of osteoarthritis: a Meta-analysis of randomized control trials
Wenzheng ZHANG ; Xuefeng LEI ; Yihui TU ; Huaming XUE
Chinese Journal of Rheumatology 2024;28(5):327-332
Objective:To evaluate the effectiveness and safety of mesenchymal stem cells (MSCs) in the treatment of knee osteoarthritis (KOA).Methods:The databases PubMed, OVID, Web of Science, CNKI, Wanfang, were systematically searched from inception to May 2023 to collect randomized control trials(RCTs) of MSCs in the treatment of KOA. The literature was selected according to the inclusion and exclusion criteria, and relevant data was extracted. Meta-analysis was conducted using RevMan 5.4 software. Heterogeneity was assessed using the I2 statistic, with the fixed effects model applied when I2 was less than 50%, and the random effects model utilized otherwise. The combined effect size and 95% confidence interval ( CI) were calculated using the inverse-variance method. Sensitivity analysis and assessment of publication bias were performed using Stata 14.0 software. Results:A total of 29 RCTs involving 1 402 participants were included. The outcomes showed that at the 12 month follow-up, MSCs reduced pain [WOMAC pain: MD(95% CI)=-4.38(-7.22, -1.55), P<0.001; VAS: MD(95% CI)=-2.00(-2.67, -1.33), P<0.001 ]. And WOMAC stiffness[WOMAC stiffness:MD(95% CI)=-1.21(-2.32, -0.10), P<0.001]; moreover, MSCs reduced KOA severity and Restored joint function, [WOMAC: MD(95% CI)=-9.40(-15.87,-2.93), P<0.001; Lequesne: MD(95% CI)=-10.57(-15.89, -5.24), P<0.001 ].And the effect lasted for at least 4 years. MRI analysis showed no significant difference between the MSC group and the control group [MD(95% CI)=-6.68 (-18.45, 5.09), P=0.270]. Subgroup analysis showed that there was no significant difference in the effects of the tissue source and dosage of MSC on osteoarthritis pain and joint function. Using WOMRS for subgroup analysis, we found that adipose tissue was the best MSCs source for cartilage repair in osteoarthritis [MD (95% CI) =-30.94(-43.87, -18.01), P<0.001]. For the occurrence of adverse events, no study had reported the occurrence of serious adverse events. Most of the adverse events were self-limited pain and discomfort, such as transient joint swelling and back pain. Conclusion:Based on current evidence, MSCs may be a safety therapy that have a good effect for OA, and the time to maintain the curative effect is no less than 4 years. There is currently no reliable evidence to address the issue of which tissue source and injection cell dosage yield the best therapeutic effect. High-quality clinical trials are needed.
5.Clinical significance of erythrocyte sedimentation rate levels in patients with systemic sclerosis
Huilin HE ; Jiaxin ZHOU ; Yong HOU ; Dong XU ; Mengtao LI ; Xiaofeng ZENG
Chinese Journal of Rheumatology 2024;28(6):361-366
Objective:To analyze the relationship between the level of erythrocyte sedimentation rate (ESR) and clinical manifestations, and to discuss the clinical significance of ESR in patients with SSc.Methods:Patients with SSc registered in Peking Union Medical College Hospital from January 2009 and May 2022 in the database of National Rheumatism Data Center (CRDC) were included. All patients fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SSc. The clinical features and laboratory tests were analyzed. T test was used for analyzing the mea-surement data with normal distribution, and the results were expressed as mean±SD deviation. Wilcoxon signed-rank test or Wilcoxon rank sum test were used to analyze the measurement data that did not conform to normal distribution. The results were expressed as M ( Q1, Q3). The count data were compared with Chisquare test or Fisher's exact test. Binary logistic regression analysiswas used to analyze independent variables. P val-ue<0.05 was considered to be statistically significant. Results:A total of 308 SSc patients were enrolled in the single center of Peking Union Medical College Hospital, including 280 females (90.9%), with the average age of (47 ±12) years old. SSc patients with elevated ESR combined woth anemia were more common. Compared with normal ESR group, elevated ESR group had higher incidence of pulmonary interstitial disease (80.8% vs. 67.6%, χ2=5.89, P=0.015), pulmonary hypertension (31.7% vs. 21.1%, χ2=4.20, P=0.040) and myositis(26.9% vs. 15.7%, χ2=5.54, P=0.019). In laboratory tests, anemia is highly frequent in SSc patients with increased ESR. The increase in CK, hs-CRP, IgA and IgG were more common, and the val-ues of IgA and IgG were sta-tistically higher. In antibody tests, anti-dsDNA antibody, anti-RNP antibody, anti-SSA and anti-SSB antibodies positivity were higher, and anti-Scl70 antibody positivity was less common ( P<0.05). Multivariate regression analysis indicated elevated IgG [ B=1.733, OR(95% CI)=5.657(2.839, 11.272), P<0.001], anemia [ B=1.083, OR(95% CI)=2.952(1.376, 6.333), P=0.005)], positive anti-SSA antibody [ B=1.665, OR(95% CI)=5.287 (2.367, 11.809), P<0.001] were independent factors for SSc patients with elevated ESR are more common. IgG and positive anti-SSA antibody were strong risk factor for increased ESR. Conclusion:SSc patients with elevated ESR are more commonl with anemia, elevated IgG and positive anti-SSA anti-body, which may be related to disease activity. Long-term follow-up for these patients is helpful to guide clini-cal doctors′ treatment choices.
6.Study on IL-18 level in patients with anti-melanoma differentiation-associated gene 5 antibodies positive dermatomyositis
Tongjun MAO ; Qian HE ; Lanlan JIA ; Xinyue ZHAO ; Yuqi XIN ; Wenfeng TAN
Chinese Journal of Rheumatology 2024;28(6):367-373
Objective:To explore the role of interleukin-18 (IL-18) in the pathogenesis of dermatomyositis (DM) associated with positive anti-melanoma differentiation-associated gene 5 antibodies(MDA5-DM).Methods:Twenty-eight cases of MDA5-DM in the department of rheumatology and immunology, the first hospital of Nanjing medical university and the first affiliated hospital od Wannan medical colledge from August 2018 to December 2011 were included in this study, comprising 15 cases with combined rapidly progressive interstitial pneumonia (RPILD) and 13 cases without RPILD (nonRPILD). Additionally, 28 cases of antisynthetase syndrome (ASS) and 28 healthy volunteers (HC) were included for comparison. Clinical, laboratory, and imaging data were collected for both the DM and ASS groups. Serum IL-18 levels were measured using ELISA. Independent t test, Mann-whitney U test, χ2 test and Fisher′s exact probability method were used for analysis. Results:Significant differences were observed in LDH, hydroxybutyrate dehydrogenase (HBDH), ESR, CRP, serum ferritin (SFE), and IL-18 levels between the MDA5-DM group, the ASS group and the HC group ( F=46.65, 43.19, 31.28, 23.94, 30.94, 49.44, all P<0.001). Additionally, lymphocyte counts and hemoglobin levels differed significantly among the three groups( F=35.26, P<0.001; F=18.59, P<0.001). MDA5-DM patients exhibited higher incidences of Gottron′s sign, helitrope rash, periungual erythema, skin ulcers, and RPILD compared to ASS patients ( χ2=20.96, P<0.001; χ2=5.85, P=0.016; χ2=13.69, P<0.001; χ2=9.16, P=0.002; χ2=4.79, P=0.029). However, the incidence of mechanic′s hand was lower in MDA5-DM patients ( χ2=3.90, P=0.048). The level of IL-18 significantly decreased in MDA5-DM after treatment[(104.28(71.96,151.10)pg/ml vs. 78.30(56.20, 94.80)pg/ml, =2.27, P=0.023)]. Similar reductions were observed in the ASS group[(72.30(61.39, 95.94)pg/ml vs. 45.30(29.00,84.10)pg/ml, Z=2.691, P=0.007]. The IL-18 level changes in the MDA5-DM combined with RPILD group were not statistically significant [99.49 (77.65, 130.87)pg/ml vs. 89.40(54.80, 120.20)pg/ml, Z=0.65, P=0.515]. In the MDA5-DM survival group, IL-18 levels decreased significantly after treatment [59.45(53.58, 81.63)pg/ml vs. 106.37(83.62, 152.07)pg/ml, Z=2.80, P=0.005], while the changes in the IL-18 levels of patients in the MDA5-DM death group were not statistically significant [99.49(56.70, 140.15)pg/ml vs. 94.80(71.40, 155.45)pg/ml, Z=1.75, P=0.080]. Conclusion:MDA5-DM patients are different from the ASS patients in clinical manifestations and indicators involved in laboratory tests. The expression level of IL-18 tends to increase during the active phase of MDA5-DM and ASS, and decrease with remission of the disease. MDA5-DM may play an important role in the pathogenesis, and persistent high level of IL-18 is responsible for RPILD and death of MDA5-DM. Sustained high level of IL-18 can be used as a potential biomarker for the estimating development of MDA5-DM into RPILD.
7.Clinical value of the adjusted global antiphospholipid syndrome score in patients with positive antiphospholipid antibodies
Xiaodan XIE ; Lanlan JI ; Zhuoli ZHANG
Chinese Journal of Rheumatology 2024;28(6):374-378
Objective:To evaluate the clinical value of the adjusted global antiphospholipid syndrome score (aGAPSS) in patients with persistent antiphospholipid antibodies (aPL).Methods:The clinical data of patients who were continuously positive for aPL from May 2012 to August 2022 were retrospectively analyzed, except for patients complicated with connective tissue diseases. Demographic data, traditional cardiovascular thrombosis risk factors, aPL profile, and clinical manifestations included and not included in antiphospholipid syndrome (APS) were collected, and aGAPSS was calculated for all patients according to risk indicators and the correlation with clinical manifestation was analyzed through rank sum test. The diagnostic value of aGAPSS for different clinical manifestations was evaluated by the receiver operator characteristic (ROC) curve.Results:A total of 67 patients with persistent aPL were enrolled, including 15 patients with persistent extra-criteria positive aPL but did not meet the APS classification criteria and 52 patients with a clear diagnosis of primary APS, of which 20 had a history of thrombosis, 36 had a history of pregnancy morbidity, and 24 had extra-criteria clinical manifestations. Patients with history of any thrombosis or arterial thrombosis scored significantly higher than those with no history of thrombosis [any history of thrombosis 11.50 (8.25, 13.00) vs 8.00 (4.00, 13.00), Z=2.33, P=0.020; arterial thrombosis history 11.00 (9.00, 14.00) vs 8.00 (4.00, 13.00), H=6.21, P=0.043]. The aGAPSS score of patients with extra-criteria clinical manifestations was significantly higher than that of patients without corresponding clinical manifestations [13.00 (8.25, 13.00) vs 8.00 (4.00, 11.00), Z=2.81, P=0.005], and the aGAPSS score of patients with thrombocytopenia was significantly higher than that of patients without thrombocytopenia [12.50 (8.00, 13.25) vs 8.00 (4.00, 13.00), Z=2.23, P=0.026]. A subgroup analysis of pregnant women found no statistically significant difference in aGAPSS scores between groups with or without a history of pregnancy morbidity. With thrombosis as the endpoint event, aGAPSS had the highest diagnostic value at 10 points(sensitivity and specificity were 65.00% and 77.78%, respectively). Conclusion:In patients with postivity aPL positivity, aGAPSS score is correlated with thrombosis history and extra-criteria clinical manifestations, especially thrombocytopenia.
8.Clinical evaluation value of CD4 + T lymphocyte subsetsin patients with recurrent uveitis in Beh?et′s disease
Shilin LU ; Na ZHANG ; Sha ZHANG ; Wei LIU ; Xiaoqing LI ; Kunping GUAN ; Jing LUO ; Xiaodong LI ; Lei SHI ; Caihong WANG
Chinese Journal of Rheumatology 2024;28(6):379-385
Objective:To evaluate the clinical value of CD4 + T lymphocyte subsets such as helper Th2 in patients with recurrent uveitis (BU) in Beh?et′s disease (BD). Methods:The clinical data of 153 hospitalized patients diagnosed with Beh?et′s disease from January 1, 2020 to June 30, 2023 in the Second Hospital of Shanxi Medical University were retrospectively analyzed. The subsets of CD4 + T lymphocytes were measured, including helper T cells (Th cells) such as Th1, Th2, Th17 and regulatory T cells (Treg cells), biochemical lipid indexes (TC, TG, etc.), the frequency of oral ulcers in the past 1 year, the frequency of genital ulcers in the past 1 year, and drug use before admission;According to whether there was ocular involvement and uveitis, 153 cases of BD were divided into Beh?et non-uveitis group (non-BU group) and Beh?et uveitis group (BU group). The above indexes and independent correlation factors of recurrent BU were compared between BU group and non-BU group;The above indexes and independent correlation factors of recurrent BU were compared between BU group and non-BU group. The levels of cytokines and ICBD total score, the correlation between ICBD total score and various cytokines, and the diagnostic performance of Th2 cells were compared between BU group and non-BU group.The statistical methods were Mann-Whitney U test, independent sample t test, Chi-square test, multiple logistic regression analysis, Pearson correlation analysis and receiver operating characteristic curve (ROC) analysis. Results:①The levels of Th1, Th2, Th17 cells, TC and TG in BU group were higher than those in non-BU group [133.87 (93.38, 229.87)/μl vs. 102.51(64.25, 149.23)/μl] and [9.43 (5.84, 14.13)/μl vs. 6.78(4.23, 9.44)/μl], [15.53 (9.36, 25.27)/μl vs. 9.83(5.46, 14.76)/μl], [4.21 (3.89, 4.90) mmol/L vs. 3.89(3.37, 4.34)mmol/L)], [1.43(1.00, 2.21)mmol/L vs. 0.96(0.69, 1.38)mmol/L], The differences were statistically significant ( Z=-3.24, Z=-3.05, Z=-3.94, Z=-2.25, Z=-3.47; all P<0.05); There was no statistical significance in Chi-square test between the two groups ( χ2=5.69, P>0.05).②The levels of IL-2, IL-10 and total ICBD score in BU group were higher than those in non-BU group, with statistical significance ( Z=-2.12, Z=-2.29, t=-6.48; all P<0.05). ③ The results of multiple logistic regression analysis showed that Th2 was an independent correlation factor for BU [ OR value (95% CI) was 1.143(1.007, 1.298), P=0.039]. The total score of BU patients was correlated with Th2 and Th17 cells. ROC analysis showed that the sensitivity of Th2 in diagnosing BU was 68.8%, the specificity was 49.5% and the area under the curve (95% CI) was 0.697 (0.585, 0.809) (P=0.001). Conclusion:CD4 + T lymphocyte subsets such as the absolute number of Th2 cells are related to BU, which is an important indicator to observe the severity of disease progression in BU patients, and has certain clinical value in evaluating the recurrence of BU in BD patients.
9.Chip analysis in exploring the pathogenesis of patients with ankylosing spondylitis
Xueting WEI ; Chaoyang LONG ; Fengzhen LI ; Zonghao WU ; Riyan ZHUGE ; Yanyun LI ; Zujie QIN
Chinese Journal of Rheumatology 2024;28(6):386-391
Objective:To explore the gene microarray of patients with ankylosing spondylitis in GEO database by using various bioinformatics methods, and to explore the possible targets and mechanisms of action.Methods:The GEO database was searched with "ankylosing spondylitis" the keyword, and the expression profile of genes related to AS was selected as the research object. Standard difference analysis, weighted co-expression analysis and gene set enrichment analysis were conducted to construct the disease set. GO and KEGG enrichment analysis were performed on the disease sets. The NCC algorithm identifies the first five key genes. THP-1 cells were implanted into RPMI-1640 culture medium containing 10% fetal bovine serum to multiply and construct the cell model of AS in vitro. The expression levels of 5 key genes were detected by qRT-PCR and Western blot. The experimental measurement data were expressed as mean± standard deviation, and the t test was used in comparison between the two groups. Results:One thousand six hundred and sixty seven disease genes were analyzed, functional annotation was mainly concentrated in 689 molecular components of cytoplasmic ribosomes, ribosomal subunits, ribosomes, cytoplasmic large ribosomal subunits, the structural composition of ribosomal REDOX enzyme activity, 1 002 molecular functions of NADH dehydrogenase activity, NADH dehydrogenase activity, and 5 764 molecular processes of mRNA catabolism and RNA catabolism The physical process involved 1 002 signaling pathways involved in Alzheimer′s disease, Prion disease, Parkinson′s disease, and the first 5 key genes were identified as RPS11, RPL4, RPL37A, RPS23, and RPS9. The experimental results were obtained by t test. The results showed that TNF-α mRNA ( t=5.59, P=0.001) and protein ( t=20.14, P<0.001) were significantly increased, indicating that LPS had induced inflammatory response in THP-1 cells, while RPL37AmRNA ( t=5.87, P=0.001), RPS11 mRNA ( t=3.88, P=0.008), RPS23 mRNA ( t=2.64, P=0.038), RPL37A protein ( t=3.18, P=0.030), RPS11 protein ( t=11.26, P<0.001), RPS23 protein ( t=5.64, P<0.001), increased, while RPS9 mRNA ( t=3.16, P=0.020), RPL4 mRNA ( t=2.54, P=0.044), RPS9 protein ( t=5.85, P<0.001) and RPL4 ( t=2.93, P=0.040) protein expressions decreased. RPL23 stimulated the joint synovial tissue to produce effect-T lymphocytes and release a large number of IL-2 and other inflammatory cytokines. RPS9 acts on the early stages of ribosomogenesis, and knocking down RPS9 reduced overall protein synthesis. RPL4 interacted with TTC22 protein to enhance the binding of WTAP mRNA to RPL4, which was associated with immune diseases. The nucleoprotein OGFOD1 catalyzed the hydroxylation of RPS23 and participated in the inflammatory process. The chromosome conformation confirmed the single nucleotide polymorphism function of IL23R genomic locus in AS disease. Conclusion:Ribosomal protein may be an important target for exploring the mechanism of AS inflammation.
10.Clinical characteristics and related factors of elbow joint disease in skeletal fluorosis
Guohua CHEN ; Aiwei HE ; Yanling WANG ; Qinglin LI ; Xiaoyan CHEN ; Xiulan FEI
Chinese Journal of Rheumatology 2024;28(6):392-397
Objective:To explore the distribution characteristics of common clinical manifestations of elbow joint in patients with endemic fluorosis and their correlation with the influencing factors.Methods:A cross-sectional survey was conducted on all permanent adult residents in 13 endemic fluorosis villages in Gaotai and Gaolan counties of Gansu province. The survey included: ① Demographic information, family history, and current medical history. ② Physical examination specifically focued on the orthopedic clinical presentations. ③Taking DR films of the forearm (including elbow joint) and calf (including knee joint), and classify the elbow joint to grade K-L based on X-ray manifestations. ④ Measuring height and weight, and calculating BMI index. ⑤Applying the Mayo elbow joint rating scale to evaluate elbow joint function. Based on the survey results, the distribution characteristics of clinical symptoms and signs of elbow joint in patients with skeletal fluorosis, as well as the distribution characteristics and correlation of factors affecting elbow joint function such as age, gender, disease course, BMI, K-L grade, etc were described. The comparison of counting data and rates were analyzed with χ2 test or Fisher exact probability test. Pearson′s test was used for correlation analysis of continuous data that conforms to normal distribution, and Spearman test was used for non-normal distribution measurement and counting data. The correlation analysis of ordered hierarchical data was conducted using Kendall′s Tau- b test. Results:①Among 501 patients with skeletal fluorosis, a total of 465 cases (92.8%) were diagnosed with elbow joint pain. A total of 185 cases (36.9%) were with elbow joint tenderness, 300 cases (59.9%) were with elbow joint enlargement, 415 cases (82.8%) were with morning stiffness of the elbow joint, 102 cases (20.4%) were with cubital tunnel syndrome, 153 cases (30.5%) were with positive forearm extensor tendon traction test, and 97 cases (19.4%) were with positive forearm flexor tendon traction test. The detection rate of elbow joint rotation limitation was the highest among those with ROM ranging from 30 ° to 70 ° (261/501, 52.1%), and the detection rate of elbow joint extension and flexion limitation was the highest among those with ROM ranging from 50 ° to 90 °(274/501, 54.7%). ②Among 501 patients with skeletal fluorosis, a total of 465 cases were found to have symptoms and positive signs in the elbow joint, with the detection rate in males being lower than that in females, with a significant difference ( χ2=41.19, P<0.001). The majority of patients were between the ages of 50 and 65 (274/501, 58.9%), with a body mass index of <18 (217, 46.67%), K-L arthritis with a radiologic grade of Ⅲ (256/501, 55.0%), and a disease course of >30 years (217/501, 46.67%). ③The correlation between clinical characteristics, the Mayo score, and various influencing factors of skeletal fluorosis found a high correlation between pain and age ( r=0.79, P<0.001) and pain and disease course ( r=0.71, P<0.001). The ROM of extension and flexion was negatively correlated with age ( r=-0.43, P<0.001), K-L grade ( r=-0.67, P<0.001), and disease course ( r=-0.48, P<0.001); Elbow tunnel syndrome was positively correlated with age ( r=0.72, P<0.001). The Mayo functional score was negatively correlated with age ( r=-0.35, P<0.001). Conclusion:Early morning stiffness of the elbow joint (<30 min), limited rotation of the elbow joint, limited extension and flexion of the elbow joint, and cubital tunnel syndrome (degree Ⅰ) have a high detection rate in the population with skeletal fluorosis. Age, course of disease, and degree of joint degeneration have a significant impact on elbow joint function in patients with fluorosis.

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