Expression of LINC00638 in rheumatoid arthritis patients with damp-heat obstruction syndrome and the regulatory mechanisms for inflammation and oxidative stress / 中南大学学报(医学版)

OBJECTIVES@#Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and joint destruction. Both inflammatory response and oxidative stress contribute to the pathogenesis of RA. Oxidative damage can induce and aggravate the imbalance of immune inflammation and promote cell and tissue damage. In this study, the expression of long non-coding RNA (lncRNA) LINC00638 in peripheral blood of patients with RA damp-heat arthralgia syndrome was observed, and the correlation between LINC00638 and disease activity, immune inflammation and oxidative stress indicator was investigated. Subsequently, the mechanisms for LINC00638 in regulating the inflammatory response and oxidative stress in RA fibroblast-like synoviocyte (FLS) under the condition of overexpression and interference were further explored.@*METHODS@#In this study, 48 RA patients with damp-heat arthralgia syndrome and 27 normal healthy subjects, who came from Department of Rheumatology, First Affiliated Hospital of Anhui University of Chinese Medicine, were included; and they were divided into a RA group and a control group. The expression of LINC00638 in peripheral blood mononuclear cells (PBMC) from the subjects was detected by real-time PCR. Enzyme linked immunosorbent assay (ELISA) was used to detect serum interleukin (IL)-10, IL-17, tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2) expression. Spearman method was used to study the relationship between LINC00638 and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP), and to observe the relation between LINC00638 and the Disease Activity Score of 28 Joint (DAS28), Quantitative Score of Damp Heat Syndrome, Visual Analogue Scale (VAS), Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS). RA-FLS was induced by RA-PBMC, and the RA in vitro cell experimental model was established. LINC00638 overexpression plasmid and small interfering RNA (siRNA) were constructed and transfected into RA-FLS. The cell experiments were divided into 4 groups: a pcDNA3. 1- control group, a pcDNA3.1-LINC00638 group, a siRNA-control group, and a siRNA-LINC00638 group. The transfection efficiency of overexpression plasmid and siRNA was detected by real-time PCR, the expression of TNF-α and IL-10 was detected by ELISA, and the expression of antioxidant proteins HO-1 and SOD2 was detected by immunofluorescence.@*RESULTS@#Compared with the control group, the expression of LINC00638 in the RA group was lower (P<0.01). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of LINC00638 was 0.9271. The DAS28 in RA group was 5.70 (5.40-6.50), the Quantitative Score of Damp-heat Syndrome was 20.0 (17.0-23.0), and the VAS score was 7.0 (6.3-8.0). Compared with the control group, the ESR, CRP, RF, anti-CCP, SAS and SDS scores in the RA group were significantly increased (all P<0.01). Spearman correlation analysis showed that: LINC00638 was negatively correlated with ESR (r=-0.532, P<0.01), CRP (r=-0.367, P<0.05), TNF-α (r=-0.375, P<0.01), MDA (r= -0.295, P<0.05), DAS28 (r=-0.450, P<0.01), and which was positively correlated with SOD2 (r=0.370, P<0.05). After the induction of RA-FLS, the expression level of LINC00638 was significantly decreased (P<0.01), indicating that the stimulation of PBMC could effectively reduce the expression of LINC00638 in RA-FLS, so the experimental model of RA-FLS-induced by PBMC was utilized. Compared with the pcDNA3.1-control group, the expressions of LINC00638, IL-10, SOD2, and HO-1 in the pcDNA3.1-LINC00638 group were significantly increased (all P<0.01), and the expression of TNF-α was decreased (P<0.01). Compared with siRNA-control group, LINC00638, IL-10, SOD2 and HO-1 in the siRNA-LINC00638 group were significantly decreased (all P<0.01), and TNF-α was significantly increased (P<0.01).@*CONCLUSIONS@#LINC00638 is down-regulated in the peripheral blood of RA patients with damp-heat arthralgia syndrome, which is correlated with disease activity, immune inflammation and oxidative stress. Overexpression of LINC00638 can down-regulate pro-inflammatory factors, up-regulate anti-inflammatory factors, and increase antioxidant enzyme activity, thereby improving inflammation and oxidative stress in RA. LINC00638 is the differential lncRNA obtained by the research group's previous high-throughput sequencing of the whole transcriptome of peripheral blood PBMCs in RA patients and validation of clinical samples. In order to deepen the molecular biology research of this gene, the microRNA and mRNA targeted by LINC00638 can be further studied from the perspective of competing endogenous RNAs.

Clinical Efficacy of Modified Zhenwutang Combined with Zhengji Technique on Cold-dampness Arthralgia Syndrome Caused by Knee Osteoarthritis at Episode / 中国实验方剂学杂志

Objective: To study the clinical efficacy of modified Zhenwutang combined with Zhengji technique on cold-dampness arthralgia syndrome caused by knee osteoarthritis (KOA) at episode and the effect on inflammatory factors of joint fluid. Method: One hundred and forty-eight patients were randomly divided into control group and observation group by random number table. Patients in control group got celecoxib capsules, 0.2 g/time, 1 time/day, and Zhengji technique with lumbar positioning oblique pulling and finger pressing for 12 times, 1 time for every two days, 3 times/week. Patients in observation group got modified Zhenwutang, 1 dose/day, and the same Zhengji technique. The course of treatment was 4 weeks. Before and after treatment, western Ontario and McMaster University Osteoarthritis index (WOMAC), pain and swelling, index of severity of osteoarthritis (ISOA), local signs of knee joint and cold-dampness obstruction syndrome were scored, and the score of quality of life were discussed by arthritis impact measurement scale 2 (AIMS2-SF). And levels of interleukin-1 beta (IL-1β), IL-17, tumor necrosis factor-alpha (TNF-α), substance P (SP) and calcitonin gene-related peptide (CGRP) were detected. Result: The clinical efficacy in observation group was better than that in control group (Z=2.131, PPPβ, IL-17, TNF-α, SP and CGRP were higher than those in control group (PConclusion: Modified Zhenwutang combined with Zhengji technique can relieve clinical symptoms of patients with cold-dampness arthralgia syndrome caused by knee osteoarthritis (KOA) at episode, ameliorate joint function to improve patients' quality of life, reduce the expression of proinflammatory factors and neuropeptides in synovial fluid, so as to inhibit the inflammatory response and controlling clinical symptoms.

Clinical observation on 42 cases of arthralgia syndrome treated by TCM syndrome differentiation and treatment / 国际中医中药杂志

Objective To observe clinical effect of treating arthralgia syndrome by syndrome differentiation and treatment of TCM.Methods 42 patients with arthralgia syndrome were randomly recruited into a control group and a treatment group.The control group was treated with routine western medicine,and the treatment group was treated with syndrome difierentiation and treatment of TCM.The clinical effect was observed in both groups after the treatment.Results The total effective rate of the treatment group and the control group was 85.7%and 66.7%respectively.The clinical effect in the treatment group was significantly higher than that of the control group(χ~2=3.126,P＜0.05).Conclusion The treatment of syndrome differentiation and treatment of TCM on arthralgia syndrome is better than routine western medicine.

Analysis of Huangqi Guizhi Wuwu Decoction in treatment of cervicalspondylotic radiculopathy with numbness / 中华中医药杂志

Numbness is a common symptom in many diseases.In terms of cognition about numbness in past dynasties,and based on clinic observation and practice,the research of Guizhi Huangqi Wuwu Decoction is necessary.As a classic prescription,it is important for doctors to concern about combination of disease and syndrome,but also attaches importance to correspondence of prescription and syndrome.