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Context: Osteoarthritis (OA) is a chronic joint disease that can eventually lead to degeneration, fibrosis, fractures, and defects of the articular cartilage. Long non-coding RNA (lncRNA) is a key substance in many processes, such as epigenetic regulation and cell-cycle and cell-differentiation modulation, and its relationship with OA has been repeatedly verified.Objective: The study intended to clarify the influence of lncRNA nuclear enriched abundant transcript 1 (NEAT1), lncRNA NEAT1, on lipopolysaccharide (LPS)-induced OA chondrocytes through sponge adsorption of microRNA-378 (miR-378) and to provide novel insights into future diagnosis and treatment of OA.Design: The research team performed an animal study.Setting: The study took place in the Department of Rehabilitation Medicine at Linyi People's Hospital in Linyi, Shangdong, China.Animals: The study's animals were 10 Sprague Dawley (SD) rats, 3-5 days old and 10-15 g in weight, of the specific-pathogen-free (SPF) grade.Intervention: The rat chondrocytes for the positive control group (the model group) were treated with 500 ng/mL of LPS to induce OA. Chondrocytes treated with the same amount of normal saline were used as the negative control group. The chondrocytes of the LPS-induced rats were into six groups: (1) a positive control group transfected with NEAT1-interfering RNA, the sh-NEAT1 group; (2) a negative control group not transfected with NEAT1-interfering RNA, the NEAT1 empty vector (NC-NEAT1) group; (3) an intervention group co-transfected with NEAT1 interfering RNA and the miR-378 inhibitor sequence (Inh-miR-378 the sh-NEAT1+ Inh-miR-378 group; (4) a negative control group transfected with NEAT1 interfering RNA but not transfected with the miR-378 inhibitor sequence, the sh-NEAT1+ miR-378 negative control (NC-miR-378) group; (5) a negative control group transfected with the miR-378 inhibitor sequence but not transfected with NEAT1 interfering RNA, the NEAT1 empty vector (NC-NEAT1) + Inh-miR-378 group; (6) a negative control group not transfected with either NEAT1 interfering RNA or the miR-378 inhibitor sequence, the NC-NEAT1 + NC-miR-378 group.Outcome Measures: An OA-chondrocyte model was induced by LPS and measurements of NEAT1 and miR-378 expression were made by real-time quantitative reverse transcription (qRT)- polymerase chain reaction (PCR). Then, small NEAT1-interfering RNA (sh-NEAT1), empty vector NEAT1 (NC-NEAT1), inhibitor-sequence-miR-378 (Inh-miR-378), and negative-control-miR-378 (NC-miR-378) were transfected into cells, and cell viability and apoptosis rate were measured. Finally, the study verified the relationship between NEAT1 and miR-378.Results: Compared to the control group, NEAT1 was significantly elevated in the model group, and its miR-378 was significantly decreased. Silencing NEAT1 can enhance OA-chondrocyte activity and decrease apoptosis. When NEAT1 and miR-378 were inhibited together, as shown fort the NC-NEAT1 + NC-miR-378 group, NEAT1 expression, as well as the multiplication and apoptosis ability of the OA-model cells, were the same as those of cells transfected with an empty vector, the NC-NEAT1 group. Also, the NEAT1 + NC-miR-378 group's cell activity was lower than that of the sh-NEAT1+NC-miR-378 group but higher than that of the NC-NEAT1 + Inh-miR-378 group. Finally, higher fluorescence activity occurred for NEAT1-mutant type (MUT) transfected with Inh-miR-378.Conclusions: NEAT1, which is highly expressed in OA, mediates LPS-induced OA-chondrocyte activity through sponge adsorption of miR-378. [ABSTRACT FROM AUTHOR]

Objectives: Arterial wall inflammation and remodelling are the characteristic features of Takayasu's arteritis (TAK). It has been proposed that vascular smooth muscle cells (VSMCs) are the main targeted cells of inflammatory damage and participate in arterial remodelling in TAK. Whether VSMCs are actively involved in arterial wall inflammation has not been elucidated. Studies have shown that cellular senescence in tissue is closely related to local inflammation persistence. We aimed to investigate whether VSMCs senescence contributes to vascular inflammation and the prosenescent factors in TAK., Methods: VSMCs senescence and senescence-associated secretory phenotype were detected by histological examination, bulk RNA-Seq and single-cell RNA-seq conducted on vascular surgery samples of TAK patients. The key prosenescent factors and the downstream signalling pathway were investigated in a series of in vitro and ex vivo experiments., Results: Histological findings, primary cell culture and transcriptomic analyses demonstrated that VSMCs of TAK patients had the features of premature senescence and contributed substantially to vascular inflammation by upregulating the expression of senescence-associated inflammatory cytokines. IL-6 was found to be the critical cytokine that drove VSMCs senescence and senescence-associated mitochondrial dysfunction in TAK. Mechanistically, IL-6-induced non-canonical mitochondrial localisation of phosphorylated STAT3 (Tyr705) prevented mitofusin 2 (MFN2) from proteasomal degradation, and subsequently promoted senescence-associated mitochondrial dysfunction and VSMCs senescence. Mitochondrial STAT3 or MFN2 inhibition ameliorated VSMCs senescence in ex vivo cultured arteries of TAK patients., Conclusions: VSMCs present features of cellular senescence and are actively involved in vascular inflammation in TAK. Vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objective: To investigate the treatment efficacy and safety of baricitinib in patients with refractory Takayasu arteritis (TAK)., Methods: We performed a prospective cohort study in which baricitinib 4 mg daily was prescribed to patients with refractory TAK, combined with oral glucocorticoids (GCs)., Results: 10 patients with refractory TAK were enrolled with a median age of 28 (IQR=22-37) years, median disease duration of 50 (IQR=24-65) months. The median dose of GCs was 10 (IQR=8.1-22.5) mg prednisone or equivalence dosage at baseline. At 6 months of baricitinib treatment, 6/10 (60%) patients had an overall treatment response. During an average follow-up of 15.3 (range 4-31) months, 4/10 (40%) patients maintained overall treatment response. 8/10 (80%) patients tapered or maintained the same dose of GCs with no change of the combined classical synthetic disease-modifying antirheumatic drugs. Two patients discontinued GCs at 18 and 24 months and were in continuous remission till the end of the study. One patient withdrew baricitinib due to liver dysfunction., Conclusion: Baricitinib 4 mg daily is effective for refractory TAK and is well tolerated., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To study the effect and mechanism of acupoint catgut embedding on patients of postmenopausal osteoporosis (PMOP)., Methods: In this prospective study, 90 patients with PMOP who received treatment in our hospital were randomly divided into the drug treatment group (n=45) and drug treatment + catgut embedding group (n=45) according to SPSS random table method. The drug treatment group was given conventional western medicine treatment, and the drug treatment + catgut embedding group was given point embedding therapy. Bone mineral density (BMD), calcium (Ca 2+ ), osteoprotegerin (OPG), estrogen (E 2 ), receptor activator of nuclear factor-kB ligand (RANKL), liver and kidney function and blood lipids were detected before treatment in the two groups, and visual analogue score (VAS) and PMOP symptom score were evaluated. The above-mentioned indexes were detected again 3 months and 6 months after treatment., Results: At 3 and 6 months after treatment, the BMD and the levels of Ca 2+ and E 2 in the two groups were increased, while the levels of OPG and RANKL were decreased, and the improvement in the drug treatment + catgut embedding group was significantly better than that in the drug treatment group (P<0.05). The symptom scores of VAS and PMOP in the drug treatment + catgut embedding group were significantly lower than those in the drug treatment group (all P<0.001). There was no significant difference in the levels of alanine aminotransferase (ALT), total bilirubin (TBil), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr) and serum uric acid (SUA) between the two groups, but the levels of total cholesterol (TC) and triglyceride (TG) in the drug treatment + catgut embedding group were significantly lower than those in the drug treatment group (all P<0.001)., Conclusion: Acupoint catgut embedding has a good effect on PMOP, and it can increase BMO and improve the clinical symptoms of patients, which is worthy of clinical promotion., Competing Interests: None., (AJTR Copyright © 2021.)

Objective To detect the level of serum proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients with systemic lupus erythematosus (SLE) and investigate the correlation between PCSK9 level and disease parameters. Methods Forty-seven SLE patients and 30 age, sex-matched healthy controls (HCs) were included in our research. Traditional cardiovascular disease (CVD) risk factors were compared between the two groups. The level of serum PCSK9 was examined by ELISA. Carotid intima-media thickness (cIMT) was measured by carotid ultrasound. According to the measured value of cIMT, SLE patients were divided into SLE-AS (cIMT≥1.0 mm) and SLE-NonAS (cIMT<1.0 mm) subgroups. Atherogenic factors and PCSK9 levels were compared between the two subgroups. Univariate correlational analysis of PCSK9 levels and disease parameters was conducted in the SLE patients. Results No difference was found in the total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ApoA1, ApoB, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), fasting blood-glucose (FBG), body mass index (BMI) or uric acid (UA) between the SLE patients and HCs. However, the higher ratio of cIMT thickening and the elevation of serum PCSK9 levels were observed in the SLE patients as compared with the HCs. No significant difference in the traditional risk factors for CVD was found, but significant difference in the level of C-reactive protein (CRP) existed between the SLE-AS subgroup and SLE-NonAS subgroup. The level of serum PCSK9 in the SLE-AS subgroup was significantly higher than that in the SLE-NonAS subgroup. PCSK9 concentrations were positively correlated with CRP levels, but not correlated obviously with the age, SLEDAI, lipids parameters (TC, LDL-C, ApoA1, ApoB, TG, HDL-C), BMI or UA levels. This tendency seemed to be more significant in the female patients. Conclusion Elevated level of serum PCSK9 can be observed in SLE patients, especially in those with thickening of cIMT. PCSK9 may be associated with atherogenic inflammation in SLE.