Fabrication of polydopamine-modified cellulose hydrogel for controlled release of α-mangostin.

Hydrogels are notable for their outstanding absorbent qualities, satisfactory compatibility with biological systems, ability to degrade, and inherent safety, all of which contribute to their high demand in the field of biomedicine. This study focuses on the fabrication of hydrogels using environmentally friendly cellulosic material. Cellulose hydrogel beads were prepared by physical cross-linking in a NaOH/urea medium. Furthermore, nano polydopamine was integrated into the hydrogel matrix as functional polymers and α-mangostin was employed as an active pharmaceutical ingredient. The physicochemical properties were comprehensively analyzed using Fourier-transform infrared spectrometer, 13C cross-polarization/magic angle spinning nuclear magnetic resonance, thermogravimetric analysis, and scanning electron microscope. The drug delivery properties, including water content, swelling ratio, and drug release profiles, were evaluated. In vitro cytotoxicity against MC3T3-E1 cells was assessed using sulforhodamine B staining. All test hydrogels exhibited inhibitory activity against the growth of MC3T3-E1 cells. These results indicated the potential use of these hydrogels as a drug delivery carrier for α-mangostin in the treatment of ankylosing spondylitis.

The Use of TNF-α Inhibitors in Active Ankylosing Spondylitis Treatment.

Ankylosing spondylitis (AS) is a challenging disease, characterized by chronic inflammation and structural damage primarily affecting the axial skeleton, while extra-articular manifestations may also appear. This results in the deterioration of patients' quality of life. Over the past few decades, tumor necrosis factor-α (TNF-α) inhibitors have revolutionized the management of AS, offering substantial relief from symptoms and improving patient outcomes. The aim of this review is to assess the efficacy of TNF-α inhibitors in patients with active AS. A search was performed in the PubMed database using the following keywords: ("TNF alpha inhibitors" OR "anti TNF-a" OR "TNF-a inhibitors" OR "anti TNF-alpha" OR "Etanercept " OR "Golimumab" OR "Infliximab" OR "Certolizumab pegol" OR "Adalimumab") AND "ankylosing spondylitis". The search was completed in February 2024, and 35 studies were included in this review following PRISMA guidelines. The findings reveal evidence supporting the efficacy of TNF-α inhibitors in reducing inflammation, preventing structural damage, and enhancing overall well-being in AS patients. Overall, TNF-α inhibitors have emerged as a cornerstone in the therapeutic algorithm against AS with a very satisfactory safety profile.

Effect of disease activity on the clinical outcome of SARS CoV-2 in patients with underlying rheumatic diseases; data from global rheumatology alliance.

Objectives: To determine the effect of disease activity on clinical outcomes of coronavirus disease-2019 in patients with rheumatic diseases. METHODS: The prospective, cohort study was conducted from January 1st to June 30th, 2021, at Rheumatology department, Fauji Foundation Hospital, Rawalpindi. It comprised patients of rheumatic disorders who were affected by coronavirus disease-2019. The patients were categorised according to rheumatic disease activity into remission group I, low disease activity group II, moderate group III and high-activity group IV. Coronavirus disease-2019 outcomes compared included recovered vs death, hospitalisation yes vs no, mechanical ventilation yes vs no. The association of disease activity status with coronavirus disease-2019 outcomes was explored. Data was analysed using SPSS 23. RESULTS: Of the 100 patients, 78(78%) were females and 22(22%) were males. The overall mean age was 45.60±13.7 years. There were 23(23%) patients in group I, 42(42%) patients in group II, 21(21%) patients in group III and 14(14%) patients in group IV. Overall,17(17%) patients died and 83(83%) patients survived. In group III, 7(33.3%) patients died, followed by 6(42.9%) in group IV (p<0.05). In total, 7(7%) patients needed mechanical ventilation, with 3(21.4%) being in group IV (p<0.05). Hospitalisation was needed in 33(33%) cases, and intergroup comparison was non-significant (p>0.05). CONCLUSIONS: Patients with severe rheumatic autoimmune disease affected by coronavirus disease-2019 were more likely to die and require invasive ventilation.

Swimming exercise alleviates pathological bone features in curdlan-injected SKG mice by inducing irisin expression.

This study assessed the therapeutic potential of swimming exercise in the curdlan-injected SKG mouse model and investigated the modulatory effects of irisin on inflammation. Curdlan-injected SKG were randomly assigned to either a home-cage group or a swimming group for 6 weeks. Changes in clinical arthritis scores and ankle thickness were measured weekly. Post-swimming program, mice were anesthetized for collection of vastus lateralis muscle and blood, which was followed by histological analysis, micro-CT imaging of the ankle joints, and the measurement of pro-inflammatory cytokines and irisin levels. Additionally, curdlan-injected SKG mice were intravenously injected with recombinant irisin protein and observed. Finally, serum levels of irisin in healthy control and ankylosing spondylitis (AS) patient groups were measured by ELISA. The swimming group of curdlan-injected SKG mice exhibited significant improvements in arthritis and enthesitis compared to the home-cage group. In particular, micro-CT and histological analyses revealed a notable reduction in pathological bone features in the swimming group compared to the home-cage group. Muscle endurance was also enhanced in the swimming group compared to the home-cage group, as determined by the wire-hanging test. Intriguingly, irisin levels not only were statistically increased in the swimming group but, also, TNF-α, IL-1ß, and IL-6 levels were decreased. Additionally, injection of irisin protein slightly attenuated both arthritis and enthesitis in curdlan-injected SKG mice. Meanwhile, irisin serum levels were declined in AS patients. Overall, we found that swimming exercise attenuated pathological bone features in an AS animal model, potentially mediated by increased irisin serum levels with associated anti-inflammatory effects.

Clinical performance of the ASAS health index in chinese patients with ankylosing spondylitis and its influencing factors.

OBJECTIVE: The aim of this study was to investigate the status of health-related quality of life in Chinese patients with ankylosing spondylitis (AS) and to analyze factors associated with the Assessment of SpondyloArthritis international Society Health Index (ASAS-HI) in AS and its relationship with disease activity and psychological status. METHODS: A cross-sectional study of 484 patients with AS attending 10 hospitals in China from March 2021 to September 2023 was recruited. The ASAS-HI assessed general health and functional status; the Depression Anxiety Stress Scales (DASS-21) assessed psychological disorders such as anxiety, depression, and stress; and the Functional Assessment of Chronic illness Therapy-Fatigue Scale (FACIT-F) assessed patients' fatigue symptoms; the Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Measurement Index (BASMI) were used to assess patients' disease activity and functional impairment. The correlation between ASAS-HI and the ASDAS, poor psychological status, and fatigue symptoms was observed. Univariate and multivariate logistic regression analyses were used to explore the relevant influencing factors of ASAS-HI. RESULTS: A total of 484 patients were included in this study of whom 162 were in poor health, 139 in moderate health, and 183 in good health. On univariate analysis, disease activity is an important factor affecting ASAS-HI. People with extremely high disease activity (ASDAS ≥ 3.5) had a 12 times elevated risk of having poor health status (OR = 12.53; P < 0.001). Other significant covariates included age ≥ 36 (OR = 1.58; P = 0.015), BMI ≥ 24 kg/m2 (OR = 2.93; P = 0.013), smoke (OR = 1.96; P = 0.002), BASFI (OR = 1.49; P < 0.001), BASMI (OR = 1.22; P < 0.001), fatigue (OR = 6.28; P < 0.001), and bad psychological conditions such as depression (OR = 10.86; P < 0.001), anxiety (OR = 3.88; P < 0.001), and stress (OR = 4.65; P < 0.001). The use of bMARDs is inversely associated with the appearance of adverse health status (OR = 0.54; P = 0.012). There was no significant relationship between HLA-B27 and sex. Multivariable logistic regression showed that higher disease activity (ASDAS ≥ 3.5) (OR = 5.14; P = 0.005), higher scores of BASMI (OR = 1.10; P = 0.009), self-reported depression (OR = 3.68; P = 0.007), and fatigue (OR = 2.76; P < 0.001) were factors associated with adverse health status. CONCLUSION: The health status of AS patients is related to age, BMI, smoking, disease activity, poor psychological status, and fatigue and is influenced by a combination of multiple factors such as emotional state, economic level, pain, and dysfunction. Therefore, clinicians should pay attention to the early assessment of ASAS-HI in order to improve the prognosis of the disease. Key Points •Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease with a long course and heavy disease burden, which greatly affects patients' quality of life. Therefore, this study aims to evaluate the health status of ankylosing spondylitis in the Chinese population and its influencing factors. •This is a multi-center cross-sectional study in China, which can better reflect the overall situation of the Chinese population.

Temporomandibular joint ankylosis suspected to be associated with ankylosing spondylitis based on cervical computed tomography images: A pictorial essay.

This report showed a case of temporomandibular joint (TMJ) ankylosis suspected to be associated with ankylosing spondylitis based on the observation of bony ankylosis of the cervical spine on computed tomography (CT) images. A 53-year-old man presented with a chief complaint of difficulty in opening his mouth. His medical history indicated that in his 20s, he became aware of the difficulty in moving his neck. CT revealed marked osteoarthritic changes in the right mandibular condyle, suggesting fibrotic TMJ ankylosis. In addition, bony ankylosis of the cervical vertebral body and facet joints from the axis (C2) to C5 in continuity was observed. CT of the entire spine also showed bony deformity of the sacroiliac joints and bony ankylosis. Based on these findings, ankylosing spondylitis was suspected. The possibility of an ankylosing spondylitis complication should be considered in cases of TMJ ankylosis if bony ankylosis of the cervical spine is observed.

[H3K27me3 Expression Level and Its Epigenetic Regulation Mechanisms in Th17 Cell Differentiation in Patients With Ankylosing Spondylitis]. / å¼ºç›´æ€§è„ŠæŸ±ç‚Žæ‚£è€ H3K27me3è¡¨è¾¾æ°´å¹³åŠå ¶è°ƒæŽ§Th17ç»†èƒžåˆ†åŒ–çš„è¡¨è§‚é—ä¼ æœºåˆ¶.

Objective: To investigate the roles of histone H3K27me3 methylation and its regulatory enzymes JMJD3 and EZH2 in the differentiation of Th17 cells in ankylosing spondylitis (AS), to unveil their potential involvement in the pathogenesis of AS, and to provide new strategies and targets for the clinical treatment of AS by analyzing the methylation state of H3K27me3 and its interactions with Th17-related factors. Methods: A total of 84 AS patients (42 active AS patiens and 42 patients in the stable phase of AS) were enrolled for the study, while 84 healthy volunteers were enrolled as the controls. Blood samples were collected. Peripheral blood mononuclear cells were isolated. ELISA assay was performed to examine Th17 cells and the relevant cytokines IL-21, IL-22, and IL-17. The mRNA expressions of RORc, JAK2, and STAT3 were analyzed by RT-PCR, the protein expressions of RORc, JAK2/STAT3 pathway protein, H3K27me3 and the relevant protease (EZH2 and JMJD3) were determined by Western blot. Correlation between H3K27me3, EZH2 and JMJD3 and the key signaling pathway molecules of Th cell differentiation was analyzed by Pearson correlation analysis. Results: The mRNA expressions of RORc, JAK2, and STAT3 were significantly higher in the active phase group than those in the stable phase group ( P<0.05). The relative grayscale values of H3K27me3 and EZH2 in the active phase group were lower than those of the stable phase group, which were lower than those of the control group, with the differences being statistically significant ( P<0.05). The relative grayscale values of JMJD3, RORc, JAK2, pJAK2, STAT3, and pSTAT3 proteins were significantly higher in the active phase group than those in the stable phase group, which were higher than those in the control group (all P<0.05). The proportion of Th17 and the expression level of inflammatory factors in the active period group were higher than those in the other two groups (P<0.05). H3K27me3 was negatively correlated with RORc, JAK2, STAT3, and IL-17, JMJD3 was positvely correlated with JAK2, STAT3, and IL-17, and EZH2 was negatively correlated with JAK2, STAT3, and IL-17 (all P<0.05). Conclusion: The low expression of H3K27me3 in AS is influenced by the gene loci JMJD3 and EZH2, which can regulate the differentiation of Th17 cells and thus play a role in the pathogenesis and progression of AS.

Itaconate is a metabolic regulator of bone formation in homeostasis and arthritis.

OBJECTIVES: Bone remodelling is a highly dynamic process dependent on the precise coordination of osteoblasts and haematopoietic-cell derived osteoclasts. Changes in core metabolic pathways during osteoclastogenesis, however, are largely unexplored and it is unknown whether and how these processes are involved in bone homeostasis. METHODS: We metabolically and transcriptionally profiled cells during osteoclast and osteoblast generation. Individual gene expression was characterised by quantitative PCR and western blot. Osteoblast function was assessed by Alizarin red staining. immunoresponsive gene 1 (Irg1)-deficient mice were used in various inflammatory or non-inflammatory models of bone loss. Tissue gene expression was analysed by RNA in situ hybridisation. RESULTS: We show that during differentiation preosteoclasts rearrange their tricarboxylic acid cycle, a process crucially depending on both glucose and glutamine. This rearrangement is characterised by the induction of Irg1 and production of itaconate, which accumulates intracellularly and extracellularly. While the IRG1-itaconate axis is dispensable for osteoclast generation in vitro and in vivo, we demonstrate that itaconate stimulates osteoblasts by accelerating osteogenic differentiation in both human and murine cells. This enhanced osteogenic differentiation is accompanied by reduced proliferation and altered metabolism. Additionally, supplementation of itaconate increases bone formation by boosting osteoblast activity in mice. Conversely, Irg1-deficient mice exhibit decreased bone mass and have reduced osteoproliferative lesions in experimental arthritis. CONCLUSION: In summary, we identify itaconate, generated as a result of the metabolic rewiring during osteoclast differentiation, as a previously unrecognised regulator of osteoblasts.

[Effects of Zhoutian moxibustion on pain symptoms and inflammatory factors in patients with ankylosing spondylitis of cold-damp obstruction].

OBJECTIVE: To observe the effects of Zhoutian moxibustion on pain symptoms and serum inflammatory factors in patients with ankylosing spondylitis of cold-damp obstruction. METHODS: Eighty-four patients with ankylosing spondylitis of cold-damp obstruction were randomly divided into a Zhoutian moxibustion group (42 cases, 2 cases dropped out) and a governor vessel moxibustion group (42 cases, 2 cases dropped out, 1 case discontinued). Both groups were given oral administration of sulfasalazine enteric-coated tablets as basic treatment. The governor vessel moxibustion group was treated with moxibustion box from Dazhui (GV 14) to Yaoyangguan (GV 3), one hour per treatment; the Zhoutian moxibustion group was treated with moxibustion box from Tiantu (CV 22) to Zhongji (CV 3) in addition to the governor vessel moxibustion group, two hours per treatment. Both groups were treated once every 3 days, twice a week, for a total of 9 weeks. The pain symptom scores of the two groups were observed before treatment and at the 3rd, 6th, and 9th weeks into treatment. ELISA was used to detect the levels of serum interleukin (IL)-1ß, IL-18, and tumor necrosis factor-α (TNF-α) before and after treatment, and the clinical efficacy of the two groups was evaluated after treatment. RESULTS: Except for the joint pain scores at the 3rd week into treatment, the total scores and the each sub-item score of pain symptom in the two groups were lower than those before treatment at the 3rd, 6th, and 9th weeks into treatment (P<0.05); at the 3rd, 6th, and 9th weeks into treatment, the total scores of pain symptom and the scores of lumbar sacral pain, back pain, joint cold pain, and limited mobility in the Zhoutian moxibustion group were lower than those in the governor vessel moxibustion group (P<0.05). After treatment, the levels of serum IL-1ß, IL-18 and TNF-α in both groups were lower than those before treatment (P<0.05), and the levels of serum IL-1ß, IL-18, and TNF-α in the Zhoutian moxibustion group were lower than those in the governor vessel moxibustion group (P<0.05). The total effective rate was 90.0% (36/40) in the Zhoutian moxibustion group, which was higher than 76.9% (30/39) in the governor vessel moxibustion group (P<0.05). CONCLUSION: Zhoutian moxibustion could effectively improve various pain symptoms in patients with ankylosing spondylitis of cold-damp obstruction, and reduce the expression of inflammatory factors.

Effects of ankylosing spondylitis on cardiovascular disease: aMendelian randomization study.

Objective: Accumulating evidence suggests that patients with ankylosing spondylitis (AS) have an elevated risk for cardiovascular disease (CVD) and cardiovascular death, however, whether AS has causal effects on the risk of CVD is unclear.Two-sample Mendelian randomization (MR) was utilizedto examine the probable causal link between them. Methods: Summary statistics from publicly released genome-wide association studies (GWAS) was used to perform MR analyses. Genetically predicted AS was selected as the exposure variable from published GWAS meta-analyses. CVD was adopted as the outcome variable. The inverse variant weighted method was employed to obtain the casual estimates. The robustness of the results was also examined by evaluating the pleiotropy and heterogeneity of single-nucleotide polymorphisms. Results: According to MR analyses, genetic susceptibility to AS was associated with a high risk of heart failure and ischemic stroke, while negativelygenetic susceptibility was found between AS and peripheral atherosclerosis. No statistical relationship was found between AS and venous thromboembolism, atrial fibrillation, coronary atherosclerosis, and valvular heart disease. Sensitivity analysis showed no evidence of horizontal pleiotropy or heterogeneity. Conclusion: The present study suggests that AS exerts causal effects on the risk of CVD, including heart failure, ischemic stroke, and peripheral atherosclerosis.

Association of ankylosing spondylitis with cardiovascular disease: a bidirectional two-sample mendelian randomization study.

Backgrounds: Current observational investigations hint at a potential linkage between ankylosing spondylitis and cardiovascular wellness. However, the nature of this causality remains to be elucidated. Consequently, this study is designed to evaluate the causal interconnection between ankylosing spondylitis and cardiovascular-related conditions utilizing a bidirectional two-sample Mendelian Randomization (MR) methodology. Methods: In this study, we conducted Mendelian randomization (MR) analyses using genome-wide association study (GWAS) data. The fixed-effects inverse variance weighted (IVW) model was used as the primary analysis method, and MR-Egger regression and the weighted median method were employed as supplementary approaches. Horizontal pleiotropy and heterogeneity were evaluated using various statistical tests, including MR-PRESSO global test, MR-Egger intercept, and Cochran's Q test. Results: The MR result demonstrated an increased risk of heart failure in individuals with ankylosing spondylitis (OR: 1.0132, 95% CI = 1.0043-1.0221, p = 0.003). The MR analysis results did not demonstrate a causal relationship between ankylosing spondylitis and other cardiovascular diseases, such as atrial fibrillation, coronary artery disease, ischemic stroke, myocardial infarction, and valvular heart disease (all p > 0.05). No evidence of reverse causality was found between ankylosing spondylitis and mentioned cardiovascular diseases in reverse MR analyses. Sensitivity analysis verified the reliability of the results. Conclusion: Our MR study indicates a relationship between ankylosing spondylitis and an increased risk of heart failure. Further research is needed to confirm these findings and elucidate the underlying mechanisms involved.

Effects of serum inflammatory factors, health index and disease activity scores on ankylosing spondylitis patients with sleep disorder.

BACKGROUND: Patients with ankylosing spondylitis (AS) frequently suffer from comorbid sleep disorders, exacerbating the burden of the disease and affecting their quality of life. AIM: To investigate the clinical significance of serum inflammatory factors, health index and disease activity scores in patients with AS complicated by sleep disorders. METHODS: A total of 106 AS patients with comorbid sleep disorders were included in the study. The patients were grouped into the desirable and undesirable prognosis groups in accordance with their clinical outcomes. The serum levels of inflammatory factors, including C-reactive protein, erythrocyte sedimentation rate, interleukin (IL)-6, tumour necrosis factor-α and IL-1ß, were measured. Disease activity scores, such as the Bath AS functional index, Bath AS disease activity index, Bath AS metrology index and AS disease activity score, were assessed. The health index was obtained through the Short Form-36 questionnaire. RESULTS: The study found significant associations amongst serum inflammatory factors, health index and disease activity scores in AS patients with comorbid sleep disorders. Positive correlations were found between serum inflammatory factors and disease activity scores, indicating the influence of heightened systemic inflammation on disease severity and functional impairment. Conversely, negative correlations were found between disease activity scores and health index parameters, highlighting the effect of disease activity on various aspects of health-related quality of life. Logistic regression analysis further confirmed the predictive value of these factors on patient outcomes, underscoring their potential utility in risk assessment and prognostication. CONCLUSION: The findings demonstrate the intricate interplay amongst disease activity, systemic inflammation and patient-reported health outcomes in AS patients complicated by sleep disorders. The results emphasise the need for comprehensive care strategies that address the diverse needs and challenges faced by these patients and underscore the potential relevance of serum inflammatory factors, health index and disease activity scores as prognostic markers in this patient population.

Health state utility values in patients with Ankylosing Spondylitis: a systematic review and meta-analysis.

INTRODUCTION: Ankylosing spondylitis (AS) is a chronic condition that requires lifelong treatment and results in a serious disease burden. Health state utility values (HSUVs) are a valuable tool for quantifying this burden and conducting cost-utility analysis. OBJECTIVE: We conducted a systematic review and meta-analysis to obtain estimates of HSUVs in patients with AS, explored potential sources of heterogeneity, and compared pooled patient HSUVs with population norms. METHOD: We searched PubMed, Embase, Web of science, Cochrane database and Scopus until July, 2023 to obtain eligible studies. The methodological quality of the included studies was assessed using the ROBINS-I checklist. RESULTS: Forty-two publications involving 11,354 participants were included in this systematic review. The most commonly used instrument is the EQ-5D (38 studies). The estimated HSUVs for patients with AS from all available studies was pooled as 0.62 (95% CI 0.59 to 0.65). The pooled mean utility estimates from the random effects meta-analysis for SF-6D, EQ-5D-3L, EQ-5D-5L, and HUI3 were 0.65 (95% CI 0.62,0.68), 0.63 (95% CI 0.59,0.66), 0.60 (95% CI 0.42,0.79), and 0.48 (95% CI 0.43,0.53), respectively. For the EQ-5D-3L we conducted stratified meta-analyses and meta-regression based on key subgroups. The pooled estimates of EQ-5D-3L were lower for patients published before 2010, with high disease activity, long duration of disease, and in developed countries. CONCLUSION: Pooled estimates of HSUVs for people with AS were substantially lower than population norms. These estimates provide robust evidence that can inform the economic evaluation of new therapies for individuals with AS.

Is there a connection between spine alignment, chest mobility, shoulder joint and respiratory parameters of patients with ankylosing spondylitis?

INTRODUCTION: Ankylosing spondylitis is chronic progressive disease, which decrease functions of musculoskeletal system including chest area. Those changes influences respiratory mechanics, worsen conditions of proper ventilation of lungs. OBJECTIVES: Rating of functional and respiratory parameters and dependence between them at patients with ankylosing spondylitis. MATERIALS & METHODS: The study included 45 patients with diagnosed ankylosing spondylitis. Chest and upper limbs mobility, resting spinal curvature alignment were assessed, and respiratory parameters were measured in a plethysmographic chamber JAGGER MasterScreen Body. RESULTS: Ankylosing spondylitis patients had lower respiratory parameters especially sReff, and FRC. Restriction of chest and upper limbs mobility was also demonstrated. Forward head extension was observed based on the occipital wall test. Correlations between functional parameters and correlations between functional and respiratory parameters were shown, in particular MIP, MEP, sReff, Rtot, TLC, ERV. CONCLUSIONS: The study confirmed a decrease in functional and respiratory parameters in the examined patients with ankylosing spondylitis compared to the applicable standards. A significant relationship was found between functional parameters in the upper body and respiratory parameters, which worsen with increasing thoracic dysfunction. The obtained results indicate the directions of therapy that should be taken into account to improve respiratory parameters and reduce respiratory dysfunction in these patients. Chest-focused physiotherapy appears to be an important element in improving function in patients with ankylosing spondylitis.

A Case of Hepatic Tuberculosis in a Patient on Adalimumab for Ankylosing Spondylitis.

Hepatic tuberculosis (TB) is an uncommon extrapulmonary manifestation of tuberculosis. Hepatic TB is more common in immunocompromised patients, such as those on immunosuppressive medications or those with a human immunodeficiency virus (HIV) infection. Primary hepatic TB is rare, and liver involvement is often secondary to spreading from the lymphatics, portal vein, or hepatic artery. We report a case of hepatic TB in a patient on adalimumab for ankylosing spondylitis (AS).

Determining the vertebra for pedicle subtraction osteotomy in surgical correction for ankylosing spondylitis with thoracolumbar kyphosis.

OBJECTIVE: This study aimed to provide a method for determining the apical vertebra for pedicle subtraction osteotomy (PSO) in corrective surgery for patients with ankylosing spondylitis (AS) with thoracolumbar kyphosis (TLK). METHODS: The medical records of AS patients with TLK who underwent PSO between May 2009 and August 2022 were retrospectively reviewed, and 235 patients were included in the study. Using the proposed method, choosing the vertebra based on Kim's apex (KA), which is defined as the farthest vertebra from a line drawn from the center of the T10 vertebral body to the midpoint of the S1 upper endplate, the authors analyzed 229 patients with apices at T12, L1, or L2 (excluding L3 because of the small sample size, n = 6). They divided all patients into two groups. Group A (n = 144) underwent PSO at the KA vertebra, while group B (n = 85) underwent PSO at a different level. Demographic and radiological data, including sagittal spinopelvic parameters of the entire spine, were collected. An additional analysis was performed on patients with the same KA vertebra. RESULTS: The vertebra distributions of patients based on KA were T12 (28 [12.2%]), L1 (119 [52.0%]), and L2 (82 [35.8%]). The corrections of sagittal vertical axis (SVA; 101.0 ± 48.5 mm vs 82.0 ± 53.8 mm, p = 0.010), global kyphosis (GK; 31.6° ± 10.0° vs 26.4° ± 10.5°, p = 0.005), and TLK (29.4° ± 10.2° vs 24.2° ± 12.9°, p = 0.012) in group A were significantly greater than those in group B, and there was no difference in the corrections of thoracic kyphosis (TK), lumbar lordosis, and pelvic incidence between the two groups. On further analysis, group A showed greater correction in TK (26.2° ± 13.7° vs 0.1° ± 8.1°, p = 0.013) for patients with T12 as the KA; greater improvements in SVA (101.5 ± 44.2 mm vs 73.4 ± 48.7 mm, p = 0.020), GK (30.6° ± 11.0° vs 25.0° ± 10.4°, p = 0.046), and TLK (32.6° ± 7.8° vs 26.7° ± 9.9°, p = 0.012) for those with L1 as the KA; and significant correction in TLK (30.0° ± 6.3° vs 4.3° ± 19.5°, p = 0.008) for patients with L2 as the KA, compared with group B. CONCLUSIONS: PSO at the apical vertebra provides a greater degree of correction of sagittal imbalance. The proposed method, selecting the vertebra based on KA, is easily reproducible for determining the apex level in AS patients with TLK.

Sex dimorphism of IL-17-secreting peripheral blood mononuclear cells in ankylosing spondylitis based on bioinformatics analysis and machine learning.

BACKGROUND: Ankylosing spondylitis (AS) with radiographic damage is more prevalent in men than in women. IL-17, which is mainly secreted from peripheral blood mononuclear cells (PBMCs), plays an important role in the development of AS. Its expression is different between male and female. However, it is still unclear whether sex dimorphism of IL-17 contribute to sex differences in AS. METHODS: GSE221786, GSE73754, GSE25101, GSE181364 and GSE205812 datasets were collected from the Gene Expression Omnibus (GEO) database. Differential expressed genes (DEGs) were analyzed with the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods. CIBERSORTx and EcoTyper algorithms were used for immune infiltration analyses. Machine learning based on the XGBoost algorithm model was used to identify the impact of DEGs. The Connectivity Map (CMAP) database was used as a drug discovery tool for exploring potential drugs based on the DEGs. RESULTS: According to immune infiltration analyses, T cells accounted for the largest proportion of IL-17-secreting PBMCs, and KEGG analyses suggested an enhanced activation of mast cells among male AS patients, whereas the expression of TNF was higher in female AS patients. Other signaling pathways, including those involving metastasis-associated 1 family member 3 (MAT3) or proteasome, were found to be more activated in male AS patients. Regarding metabolic patterns, oxidative phosphorylation pathways and lipid oxidation were significantly upregulated in male AS patients. In XGBoost algorithm model, DEGs including METRN and TMC4 played important roles in the disease process. we integrated the CMAP database for systematic analyses of polypharmacology and drug repurposing, which indicated that atorvastatin, famciclocir, ATN-161 and taselisib may be applicable to the treatment of AS. CONCLUSIONS: We analyzed the sex dimorphism of IL-17-secreting PBMCs in AS. The results showed that mast cell activation was stronger in males, while the expression of TNF was higher in females. In addition, through machine learning and the CMAP database, we found that genes such as METRN and TMC4 may promote the development of AS, and drugs such as atorvastatin potentially could be used for AS treatment.

Sex-specific impact of inflammation on traditional cardiovascular risk factors and atherosclerosis in axial spondyloarthritis. A multicentre study of 913 patients.

INTRODUCTION: The nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and sex differences in this regard are yet to be assessed. METHODS: Study including 611 men and 302 women from the Spanish multicentre AtheSpAin cohort to assess CV disease in axSpA. Data on CV disease risk factors were collected both at disease diagnosis and at enrolment, and data on disease activity, functional indices and carotid ultrasonography only at enrolment. RESULTS: After a median disease duration of 9 years, patients of both sexes who at disease diagnosis had elevated acute phase reactants (APRs), more frequently had hypertension and obesity. The same occurred with dyslipidaemia in men and with diabetes mellitus in women. At enrolment, CV risk factors were independently associated with APR and with activity and functional indices, with various sex differences. C reactive protein (CRP) values were inversely associated with HDL-cholesterol in men (ß coefficient: -1.2 (95% CI: -0.3 to -0.07) mg/dL, p=0.001), while erythrocyte sedimentation rate values were positively associated with triglycerides in women (ß coefficient: 0.6 (95% CI: 0.04 to 1) mg/dL, p=0.035). Furthermore, only women showed an independent relationship between insulin resistance parameters and APR or disease activity. Both men and women with high-very high CV risk according to the Systematic Assessment of Coronary Risk Evaluation 2 and CRP levels higher than 3 mg/L at diagnosis of the disease presented carotid plaques significantly more frequently than those with normal CRP levels at disease diagnosis. CONCLUSION: Inflammation is associated with atherosclerosis and CV disease in axSpA. A gender-driven effect is observed in this relationship.

Genetic overlap between psoriatic arthritis and ankylosing spondylitis in a Chinese population.

Previous studies reveal that psoriatic arthritis (PsA) and ankylosing spondylitis (AS) share susceptibility genes, such as HLA-B27, demonstrating a degree of genetic overlap between these diseases. Recent studies have identified a number of novel AS and PsA genetic susceptibility loci, but data on these loci in Chinese PsA patients are limited. To identify candidate genes that confer susceptibility to PsA in Chinese patients with PsA, psoriasis vulgaris (PsV), and healthy controls. Sixteen susceptibility loci, reported in a genome-wide association study of AS, and nine susceptibility loci, reported in candidate gene studies of PsA, were examined. Single-nucleotide polymorphisms (SNPs) were genotyped in 503 patients with PsA, 496 patients with PsV, and 979 healthy controls using the SNPscanTM multiplex SNP genotyping platform. PLINK software and logistic regression analysis were used to estimate the statistical significance of associations. PPP2R3C (rs8006884) was shown to significantly associate with PsA+PsV (p = 1.92×10-3, OR = 1.28) and was suggested to associate with PsV (p = 0.03, OR = 1.19). A suggestive association was also observed between IL-23R (rs12141575) and PsA as well as with axial PsA based on subtype analysis, KIF3A (rs2897442) and PsV, and ERN1 (rs196941) or IFIH1 (rs984971) and axial PsA. Our results suggest that PPP2R3C confers susceptibility to PsA and PsV, and that this gene may be related to the pathogenesis of psoriatic lesions and arthritis. Moreover, our results indicate a possible association between IL-23R, ERN1, or IFIH1 and subtypes of PsA, and between KIF3A and PsV.

Evaluation of PD-1 Gene Expression Profile and Methylation of the Regulatory Regions in Patients with Ankylosing Spondylitis.

Background: Ankylosing spondylitis (AS) is a chronic autoimmune disorder characterized by the fusion of vertebral joints and axial arthritis. The programmed death-1 (PD-1) inhibitory receptor has a pivotal role in controlling T cell function and may have a significant impact on the pathogenesis of autoimmune diseases such as AS pathogenesis. Objective: To investigate PD-1 gene expression and its epigenetic regulation by detecting methylated CpG islands in the regulatory sites of the gene. This will provide insight into the mechanisms involved in the disease. Methods: 30 AS patients and 30 healthy individuals were examined to detect the 16 CpG islands in intron 1 using bisulfite conversion and methylation-specific PCR technique. In addition, RNA samples were isolated from fresh peripheral blood mononuclear cells (PBMCs), and after complementary DNA (cDNA) synthesis, the expression level of the PD-1 gene was evaluated using Real-Time PCR. Results: The CpG islands located in the intronic zone of the PD-1 gene were hyper-methylated in both the patients with AS and the healthy controls. The gene expression of PD-1 was significantly downregulated in AS patients compared with the controls (p=0.017). A negative correlation between the Bath Ankylosing Spondylitis Disease Activity Index and PD-1 gene expression was also revealed. Conclusion: The low level of PD-1 gene expression is implicated in the pathogenesis of AS. However, in both groups, the methylation level of the intron 1 CpG islands of the PD-1 gene suggests that other regulatory mechanisms are more relevant to PD-1 gene expression than methylation in the intron.