Network pharmacology-based strategy to investigate the mechanisms of artemisinin in treating primary Sjögren's syndrome.

OBJECTIVE: The study aimed to explore the mechanism of artemisinin in treating primary Sjögren's syndrome (pSS) based on network pharmacology and experimental validation. METHODS: Relevant targets of the artemisinin and pSS-related targets were integrated by public databases online. An artemisinin-pSS network was constructed by Cytoscape. The genes of artemisinin regulating pSS were imported into STRING database to construct a protein-protein interaction (PPI) network in order to predict the key targets. The enrichment analyses were performed to predict the crucial mechanism and pathway of artemisinin against pSS. The active component of artemisinin underwent molecular docking with the key proteins. Artemisinin was administered intragastrically to SS-like NOD/Ltj mice to validate the efficacy and critical mechanisms. RESULTS: Network Pharmacology analysis revealed that artemisinin corresponded to 412 targets, and pSS related to 1495 genes. There were 40 intersection genes between artemisinin and pSS. KEGG indicated that therapeutic effects of artemisinin on pSS involves IL-17 signaling pathway, HIF-1 signaling pathway, apoptosis signaling pathway, Th17 cell differentiation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Molecular docking results further showed that the artemisinin molecule had higher binding energy by combining with the key nodes in IL-17 signaling pathway. In vivo experiments suggested artemisinin can restored salivary gland secretory function and improve the level of glandular damage of NOD/Ltj mice. It contributed to the increase of regulatory T cells (Tregs) and the downregulated secretion of IL-17 in NOD/Ltj model. CONCLUSION: The treatment of pSS with artemisinin is closely related to modulating the balance of Tregs and Th17 cells via T cell differentiation.

Disease Duration Affects the Clinical Phenotype of Primary Sjögren Syndrome: A Medical Records Review Study of 952 Cases.

OBJECTIVES: To investigate the impact of disease duration on clinical phenotypes in Chinese patients with primary Sjögren syndrome (pSS) and examine the correlation between clinical phenotypes and onset age, age at diagnosis, and disease duration. METHODS: Data from 952 patients diagnosed with pSS in China between January 2013 and March 2022 were analyzed based on medical records. Patients were categorized into 3 groups based on disease duration: short (<5 years), moderate (≥5 and <10 years), and long (≥10 years) group. Clinical characteristics were compared among the 3 groups, and pSS patients with a long disease duration were compared with the other patients after matching age at diagnosis and age at onset. RESULTS: Among the patients, 20.4% had a disease duration over 10 years. After matching for age at onset and age at diagnosis, pSS patients with a long disease duration exhibited a significantly higher prevalence of dry mouth ( p <0.001), dry eyes ( p <0.001), fatigue ( p <0.001), arthralgia ( p <0.001), and dental caries ( p <0.001) and higher rates of anti-Sjögren syndrome A ( p < 0.05), anti-Ro52 ( p < 0.05), and anti-SSB ( p < 0.05) positivity than their control groups, with prevalence increasing with disease duration ( ptrend < 0.001). However, no differences were noted in the prevalence of interstitial lung disease and leukopenia between different disease duration groups after matching for age at onset, although differences were shown when matching for age at diagnosis. CONCLUSION: Longer disease duration in pSS patients correlates with increased prevalence of sicca symptoms, fatigue, and arthralgia and higher positivity of autoantibodies associated with pSS. However, the prevalence of interstitial lung disease and leukopenia did not correlate with disease duration after matching for age at onset.

Sex Difference in Primary Sjögren Syndrome: A Medical Records Review Study.

OBJECTIVES: The aim of this study was to study clinical and biological differences between men and women with primary Sjögren syndrome (pSS) in China and perform a literature review to confirm if the clinical phenotypes are affected by sex in patients with pSS. METHODS: Data from 961 patients with pSS treated at a tertiary hospital in China between January 2013 and March 2022 were analyzed based on medical records. Clinical characteristics, including disease manifestations and serological parameters of the disease, were compared between men and women with pSS using the Mann-Whitney U test and χ 2 test. RESULTS: This study included 140 (14.6%) men and 821 (85.4%) women with pSS. Women with pSS demonstrated a higher prevalence of dry mouth, dry eyes, arthralgia, and dental caries ( p < 0.05); higher erythrocyte sedimentation rate and immunoglobulin M levels ( p < 0.05); higher prevalence of leukopenia, neutropenia, anemia, low complement 3, and low complement 4 ( p < 0.05); and higher titers of antinuclear antibody, anti-Sjögren syndrome A, anti-Ro52, and rheumatoid factor positivity ( p < 0.05) than men, whereas men with pSS had a higher prevalence of parotid enlargement and interstitial lung disease ( p < 0.05). CONCLUSIONS: Women with pSS are associated with more dryness, cytopenia, hypocomplementemia, and autoantibody positivity. Although men with pSS probably have lighter sicca symptoms and lower immunoactivity and serologic responses, regular monitoring of interstitial lung disease in men is vital.

Factors associated with secondary immune thrombocytopenia in patients with primary Sjögren's syndrome: a retrospective study of 639 cases.

OBJECTIVES: To investigate the clinical characteristics and relevant factors of secondary immune thrombocytopenia (ITP) in patients with primary Sjögren's syndrome (pSS). METHODS: Patients with pSS being treated between 2013 and 2020 in China-Japan Friendship Hospital were retrospectively analysed. Clinical characteristics were compared between pSS patients with and without secondary ITP. Logistic regression analysis was performed to identify factors associated with secondary ITP in patients with pSS. RESULTS: 639 patients with pSS were included in this study, among which 566 (88.6%) were women. The prevalence of secondary ITP in patients with pSS were 12.4%. Among pSS patients with secondary ITP, 55.7% had mucocutaneous bleeding and 8.9% experienced visceral bleeding. Lymphopenia (OR=3.154, 95% CI 1.185-8.395, p=0.021), anaemia (OR=2.416, 95% CI 1.250-4.668, p=0.009), low C4 (OR=2.904, 95% CI 1.563-5.394, p=0.001), and positive anti-RNP (OR=2.777, 95% CI 1.070-7.202, p=0.036) were significantly related to secondary ITP, while interstitial lung disease (ILD, OR=0.429, 95% CI 0.203-0.907, p=0.027), ANA ≥1:320 (OR=0.469, 95% CI 0.221-0.996, p=0.049) and positive anti-SSB (OR=0.288, 95% CI 0.126-0.685, p=0.003) were negatively associated with secondary ITP in patients with pSS. CONCLUSIONS: Over 10% of patients with pSS had secondary ITP, among whom visceral bleeding was comparatively rare. Lymphopenia and anaemia were positively related to secondary ITP, while ILD was negatively associated with secondary ITP. Low C4 and positive anti-RNP seem to be two potential risk factors for secondary ITP in patients with pSS, while ANA ≥1:320 and positive anti-SSB may be two potential protective factors.

Distinct clinical phenotypes of primary Sjögren's syndrome differ by onset age: a retrospective study of 742 cases and review of the literature.

OBJECTIVES: To study the clinical characteristics of primary Sjögren's syndrome (pSS) with different onset age, and perform a review of the literature to confirm if the clinical phenotypes are affected by onset age in patients with pSS. METHODS: Data of 742 patients with pSS were retrospectively analysed. Patients were divided into three groups according to onset age: young-onset pSS (YopSS, <35 years), adult-onset pSS (AopSS, ≥35 and ≤65 years), and elderly-onset pSS (EopSS, >65 years). Clinical characteristics were compared among three groups and further multiple comparisons were conducted by Bonferroni adjustment. The Chi-squared test for linear-by-linear association was used to explore variation tendency. RESULTS: This study included 105 (14.2%), 533 (71.8%), and 104 (14.0%) cases of YopSS, AopSS, and EopSS, respectively. YopSS demonstrated lower prevalence of dry mouth, abnormal Schirmer I tests, and interstitial lung disease (ILD), but higher proportions of low C3 and C4 levels, and ANA, anti-SSA, anti-SSB, and rheumatoid factor (RF) positivity than AopSS and EopSS. The proportions of dry mouth (p=0.004), abnormal Schirmer I tests (p=0.002), and ILD (p<0.001) tended to increase with the increase of onset age, while the prevalence of leukopenia (p=0.011), low C3 (p=0.001), low C4 (p=0.001), and ANA (p<0.001), anti-SSA (p<0.001), anti-SSB (p<0.001) and RF (p<0.001) positivity tended to decrease with an increase in onset age. CONCLUSIONS: YopSS demonstrated less dryness and ILD, but more immunologic disorders. ILD prevalence were directly proportional to onset age of pSS; however, leukopenia, hypocomplementaemia, and autoantibody positivity showed opposite trends.

The validity and reliability of quality of life questionnaires in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a systematic review and meta-analysis.

BACKGROUND: Patients who suffered from ankylosing spondylitis (AS) or non-radiographic axial spondyloarthritis (nr-axSpA) often have poor quality of life (QoL) and there has been a substantial increase in research on acceptable questionnaires for assessment of QoL. This systematic review aims at examining the validity and reliability of QoL questionnaires in patients with AS/nr-axSpA. METHODS: Randomized controlled trials (RCTs), cohort trials, and cross-sectional trails were retrieved by searching seven databases. Primary outcomes included test-retest reliability and construct validity. Secondary outcomes included internal consistency, structural validity, responsiveness and so on. Data extraction and analyses were conducted according to the Cochrane standards. The Agency for Healthcare Research and Quality (AHRQ) checklists was used to assess the risk of bias for each included study. We used the Consensus-based Standards for the Selection of Health Status Measurement Instruments (COSMIN) to assess the methodological quality and measurement property of included instruments. The quality of evidence on pre-specified outcomes were assessed by the Grades of Recommendations, Development and Evaluation (GRADE) approach. RESULTS: 22 publications containing 10 self-rating instruments were included in this study. Most studies were cross-sectional in design and a total of 3,085 participants were enrolled. 19 studies had moderate to high test-retest reliability. Cronbach's alpha (α) Coefficients were generally high (0.79-0.97) for overall scales. The ankylosing spondylitis quality of life (ASQOL) and evaluation of ankylosing spondylitis quality of life (EASi-QoL) questionnaires showed the strongest measurement properties in high-quality studies. The correlation coefficient for test-retest reliability of the ASQOL questionnaire was 0.85 (95% CI 0.80 to 0.89). The pooled Cronbach's α coefficients of the ASQOL questionnaire and the EASi-QoL questionnaire were high. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were considered as two validity criteria. For the ASQOL and EASi-QoL questionnaire, pooled convergent validity associations with BASDAI and BASFI were low to strong (0.24-0.81). CONCLUSIONS: This study indicated acceptable reliability and stability of included QoL questionnaires. The ASQOL and the EASi-QoL questionnaires are validated and reliable disease-specific questionnaires for the assessment of QoL in patients with AS/nr-axSpA.

Predictive value of the TyG index and rheumatoid factor for cardiovascular disease risk in a rheumatoid arthritis population: data from a survey of 418 patients.

OBJECTIVE: To investigate the correlation between the triglyceride-glucose (TyG) index and rheumatoid factor levels and the existence of cardiovascular disease in patients in the rheumatoid arthritis population and to analyze their potential value in predicting the risk of cardiovascular disease. METHODS: Patients with rheumatoid arthritis treated by the Traditional Chinese Medicine Department of Rheumatism of the China-Japan Friendship Hospital from 2019-01 to 2021-12 were included in this retrospective study. Regression analysis was performed with multifactor-corrected multimodal logistic models to observe the correlation between the TyG index and rheumatoid factor and cardiovascular disease risk, construct predictive models and assess the potential predictive value of the variables on cardiovascular disease risk with receiver operating characteristic curves. The results were further corrected by sensitivity analysis and trend tests. RESULTS: A total of 418 patients with rheumatoid arthritis were included in the study. In the rheumatoid arthritis population, high rheumatoid factor (OR = 1.002, 95% CI = 1.001-1.002, P < 0.001), high TyG index (OR = 1.057, 95% CI = 1.008-1.109, P = 0.022), advanced age (OR = 1.080, 95% CI = 1.050-1.112, P < 0.001), and low physical activity (OR = 2.848, 95% CI = 1.195-6.785, P = 0.018) were independent risk factors for the existence of cardiovascular disease in patients. The combined coefficient calculated on the basis of the TyG index and rheumatoid factor was used to plot the receiver operating characteristic curve with an area under the curve of 0.791, which can be used to predict the potential risk of cardiovascular disease in patients with rheumatoid arthritis. Further sensitivity analysis found that the marker of focus remained associated with cardiovascular disease risk in a high-physical activity population with rheumatoid arthritis. The final trend test found a linear trend between the TyG index, rheumatoid factor levels and the risk of cardiovascular disease. CONCLUSION: In the rheumatoid arthritis population, the TyG index and rheumatoid factor have some potential predictive value in determining the risk of cardiovascular disease, and the predictive efficacy is better when the two tests are combined.

Research on primary Sjögren's syndrome in 2004-2021: a Web of Science-based cross-sectional bibliometric analysis.

The extent, range, and nature of available research in the field of primary Sjögren's syndrome (pSS) have not been understood fully. This study aimed to map the literature available on pSS, and identify global hotspots and trends in the research. Papers on pSS published between 2004 and 2021 were searched from Web of Science Core Collection. The quantity and citations of publications, and the research hotspots and trends in the field of pSS were analyzed and presented visually by Microsoft Excel and Citespace software. A total of 3606 papers mainly from 526 institutions in 83 countries/regions were included for analysis. The number of publications presented an overall upward trend in the field of pSS from 2004 to 2021. The USA ranked first in the number of publications (n = 661), followed by China (n = 491), Italy (n = 405), France (n = 351), and Japan (n = 292). Moreover, seven of the top ten countries by the number of publications on pSS were from Europe. The University of Groningen (n = 661), Xavier Mariette (n = 95), and Clinical and Experimental Rheumatology (n = 184) were the most prolific affiliation, author, and journal, respectively. Vitali C (n = 2009) and Arthritis and Rheumatism (n = 3918) held the record for the most cited papers by an author and journal, respectively. At present, the hot keywords in the field of pSS include disease activity, ultrasonography, management, consensus, and data-driven. Lymphoid organization, clinical phenotypes outcome, salivary gland ultrasonography, and Toll-like receptor are the emerging research trends in pSS. Research on pSS is flourishing. Current research of pSS mainly focuses on disease activity, ultrasonography, and management. While, the emerging research trends in pSS are lymphoid organization, clinical phenotypes outcome, salivary gland ultrasonography, and Toll-like receptor.

Risk Factors for Spinal Structural Damage in a Chinese Cohort With Ankylosing Spondylitis.

OBJECTIVES: A cross-sectional study was conducted in 270 Chinese patients with ankylosing spondylitis (AS) in order to identify potential risk factors for severity of spinal structural damage. METHODS: Two hundred seventy AS patients fulfilled the Modified New York Criteria. Computed tomography (CT) was used to scan sacroiliac and hip joints, and radiography was used to scan anteroposterior and lateral lumbar spine, as well as lateral cervical spine. Bath Ankylosing Spondylitis Radiology Index and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) were scored in duplicate. RESULTS: One hundred eighty-three patients had low mSASSS (mSASSS, <10), and 87 patients had high mSASSS (mSASSS, ≥10). Univariate analysis revealed that AS age of onset, body mass index (BMI), smoking duration, duration of symptoms, diagnostic delay, hip involvement, and sacroiliitis grade were significantly associated with the risk of having high mSASSS after adjustment (all p's < 0.05). Hip involvement interacted significantly with BMI and smoking duration in a graded manner. Particularly, relative to patients with low BMI-negative hip involvement, those with high BMI-negative hip involvement, low BMI-positive hip involvement, and high BMI-positive hip involvement had a 1.94-fold, 3.29-fold, and 5.07-fold increased risk of high mSASSS (95% confidence interval, 0.84-4.47, 1.37-7.89, and 1.97-13.06, p = 0.118, 0.008, and 0.001, respectively). Finally, a nomogram graph based on 7 significant risk factors was generated with substantial prediction accuracy (concordance index, 0.906). CONCLUSIONS: We have identified 7 potential risk factors for the severity of spinal structural damage in Chinese AS patients. Importantly, positive hip involvement, combined with high BMI or long smoking duration, was associated with a remarkably increased risk of having severe spinal structural damage.

Predisposition of six well-characterized microRNAs to syndesmophytes among Chinese patients with ankylosing spondylitis.

OBJECTIVES: We quantified the expression of six well-characterized microRNAs (miRNAs) in peripheral blood mononuclear cells to see whether they can predispose to syndesmophytes in ankylosing spondylitis (AS) patients. METHODS: This is a cross-sectional study involving 46 AS patients (23/23 with/without syndesmophytes) and 22 healthy controls. miRNAs expression was quantified by real-time PCR. RESULTS: Six examined miRNAs were comparably expressed between AS patients without syndesmophytes and healthy controls (p > .05). Relative to AS patients without syndesmophytes, patients with syndesmophytes had significantly higher levels of miR-29a, miR-335-5p, miR-27a and let-7i (p = .001, .002, .013 and .029, respectively). Nine significant contributors associated with syndesmophytes in AS, including smoking, AS duration, human leukocyte antigen B27, erythrocyte sedimentation rate, C-reactive protein, miR-335-5p, miR-27a, miR-218 and sacroiliitis, were identified. The addition of miR-335-5p, miR-27a and miR-218 can significantly improve the accuracy of baseline risk factors. Based on the nine significant contributors, a nomogram was constructed, with good prediction accuracy (C-index: 0.86, p < .001). CONCLUSION: We provide evidence for the predisposition of miR-335-5p, miR-27a and miR-218 to syndesmophytes in AS patients, indicating a contributory role of miRNAs in the pathogenesis of syndesmophytes. Further validation is warranted.

[Effect of Bushen Qiangdu Recipe on Histomorphology and Wnt Pathway of DBA/1 Mice].

Objective To observe the effect of Bushen Qiangdu Recipe (BQR) on the entheses ossification histomorphology of articular ligament of DBA/1 mice with spontaneous ankylosing spondylitis (AS) , and to study its mechanism for prevention and treatment of AS. Methods Thirty 12-week old male DBA/1 mice were randomly divided into the model group, the positive drug group, low, medium, high dose BQR groups, 6 in each group. Another 6 C57BLE mice of the same age were recruited as a blank control group. BQR containing 11. 25, 22. 50, 45.00 g/kg crude drugs was respectively adminis- tered to mice in low, medium, high dose BQR groups by gastrogavage, 0. 2 mL for each mouse, once per day. Celecoxib Capsule (0. 2 mL/0. 8 mg for each mouse, once per day) was administered to mice in the positive drug group by gastrogavage. Equal volume of normal saline was administered to mice in the model group and the blank control group by gastrogavage. All mice were fed and intragastically adminis- tered for 12 successive weeks. Body weight, diet, stools, and hair were routinely observed. Signs of ar- thritis were evaluated once per two weeks. Mice were sacrifice, and then general observation of achilles tendon was performed. The achilles tendon tissue was HE stained. Protein expressions of alkaline phos- phatase (ALP) , bone gamma-carboxyglutamic-acid-containing proteins (BGP) , Dickkopfl (DKK1) , and Wnt5a in the achilles tendon were detected using immunohistochemical method. Results Compared with the blank control group, the scoring of arthritis obviously increased in the model group (P <0. 05). But the scoring of arthritis was obviously lower in the 3 BQR groups and the positive drug group than in the model group (P <0. 05). Histopathological results of achilles tendon tissue showed that no infiltration of inflammatory cells or fibroblasts occurred in the normal group. Their histomorphological structures were normal. Cartilage formation and bone formation at various degrees occurred in the model group. Filtration of fibroblast-like cells occurred in inflammatory cells and attachment points. Scattered lymphocyte infiltra- tion was often seen in the achilles tendon tissue of each medicated group. Cartilage formation and bone formation were rarely seen. Compared with the blank control group, the scoring of arthritis increased in the model group (P <0. 05). Compared with the model group, the scoring of arthritis was decreased in the 3 BQR groups and the positive drug group (P <0. 05). Compared with the blank control group, protein expression of DKK1 decreased and protein expression of Wnt5a increased in the model group (P <0. 05). Compared with the model group, protein expression of DKK1 increased and protein expression of Wnt5a decreased in middle and high dose BQR groups (P <0. 05). Conclusion BQR could delay the occur- rence and development of arthritis and ossification in DBA/1 mice of spontaneous AS model possibly by inhibiting classical Wnt pathway.

PREDICTIVE PHARMACOKINETICS OF TRAMADOL HYDROCHLORIDE FLOATING TABLETS.

The purpose of this study was to propose the effectiveness of convolution approach to predict pharmacokinetics of tramadol hydrochloride floating tablets, prepared by using various ratios of carbopol, HPMC K100M, and Hibiscus rosa Sinensis as excipient. The in vitro dissolution test was conducted using paddle method in 900 mL of HCl buffer with pH 1.2 to simulate the gastric condition. The stirring speed of paddles was set at 70 rpm. Temperature of dissolution medium was adjusted at 37 ± 5 °C. At predetermined time points, 5 mL of dissolution samples were taken with a replacement of same volume using fresh medium. The obtained samples were analyzed at 271 nm using UV visible spectrophotometer. The values of predicted pharmacokinetic parameters like Cmax (maximum blood drug level), Tmax (time required to attain maximum blood drug level), and AUC (area under blood drug concentration curve) ranged between 80.8 ± 3.2-119.6 ± 4.7 ng/mL, 11.4 ± 0.2-12.2 ± 0.2 h, and 1430.5 ± 209.5-1970.6 ± 287.4 ng.h/mL, respectively. This certainly is a desired feature required at the formulation development step, where the formulator requires the development of a formulation using desired in vivo features on the basis of only accessible in vitro data. It can be concluded from the results that convolution method is a practical method for the prediction of drug concentration in blood and for quality control.

[Efficacy and Safety Evaluation of Bushen Shuji Granule in Treating Ankylosing Spondylitis Patients: a Clinical Study].

OBJECTIVE: To evaluate the short-term efficacy and safety of Bushen Shuji Granule (BSG) in treating ankylosing spondylitis (AS) patients. METHODS: A prospective randomized controlled clinical trial was carried out in 62 active stage AS patients with Shen deficiency Du-channel cold syndrome (SDDCS), who were randomly assigned to the BSG group (treated with BSG) and the control group (treated with Celecoxib Capsule). Twelve weeks consisted of one therapeutic course. Therapeutic effects were evaluated by ASAS20 and ASAS40 (set by Assessments in Ankylosing Spondylitis working group) , BASDA150, Chinese medical (CM) syndrome efficacy evaluation standards. BASDAI, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath AS Metrology Index (BASMI), scores for spine pain, scores for pain at night, patient global assessment (PGA) , erythrocyte sedimentation rate (ESR) , and C reactive protein (CRP) were observed before and after treatment. RESULTS: After three-month treatment by BSG, ASAS20 standard rate was 63. 33% (19/30 cases) in the BSG group and 66.67% (20/30 cases) in the control group with no significant difference between the two groups (χ2 = 0.073, P > 0.05). The efficacy for CM syndromes was 70.00% (21/30 cases) in the BSG group, higher than that in the control group [40.00% (12/30 cases), χ2 = 5.455, P < 0.05]. Scores for CM syndromes, BASDAI, night pain index, spinal pain index, PGA, CRP were improved in the BSG group (P < 0.05, P < 0.01). The incidence of adverse events in the BSG group was lower than that of the control group. CONCLUSION: BSG based on Shen supplementing, Du-channel strengthening, blood activating, and channels dredging method had good short-term clinical efficacy and safety in treating AS.

[Manifestations of rheumatoid arthritis patients of cold syndrome and heat syndrome using wrist ultrasound].

OBJECTIVE: To explore distinctive manifestations of rheumatoid arthritis (RA) patients of cold syndrome and heat syndrome using wrist joints ultrasound. METHOD: s Totally 65 RA patients were syndrome typed as cold syndrome (29 cases, cold-damp blockage syndrome) and heat syndrome (36 cases, damp-heat obstruction syndrome). Grey-scale synovitis, power doppler (PD) signals, tenosynovitis, and bone erosion were observed using wrist ultrasound. Distinctive manifestations of cold syndrome and heat syndrome were analyzed using wrist ultrasound. RESULTS: In RA patients of cold syndrome, the positive rate of synovitis, PD, tenosynovitis, and bone erosion was 51.72%, 20.68%, 51.72%, and 37.93%, respectively, while they were 97.22%, 91.67%, 75.0%, and 63.89%, respectively in RA patients of heat syndrome. Compared with patients of cold syndrome, the positive rate of synovitis, PD, and bone erosion increased in patients of heat syndrome (P < 0.01, P < 0.01, P < 0.05). There was no statistical difference in the positive rate of tenosynovitis between the two groups (P > 0.05). Compared with the cold syndrome group, there was statistical difference in the constituent ratio of synovitis, PD, and bone erosion in the heat syndrome group (P < 0.01, P < 0.01, P < 0.05), but with no statistical difference in the constituent ratio of tenosynovitis (P > 0.05). Results of the ROC curve showed that the sensitivity was 86.1% and the specificity was 62.1% in judging heat syndrome, when the total score of synovitis in two wrists was more than 1.5; the sensitivity was 80.0% and the specificity was 93.1% in judging heat syndrome, when the total score of PD in two wrists was more than 1.5. CONCLUSIONS: Positive rates of synovitis, PD, and bone erosion were significantly higher in RA patients of heat syndrome than those of cold syndrome. Especially serious manifestations were more often seen in RA patients of heat syndrome. The total score of synovitis or PD in the two wrist joints higher than 1.5 was characteristic manifestations of heat syndrome using wrist ultrasound.

Hierarchically spherical assembly of carbon nanorods derived from metal-organic framework as solid-phase microextraction coating for nitrated polycyclic aromatic hydrocarbon analysis.

Nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) are pervasive contaminants in aquatic environments. They are characterized by persistence, toxicity, bioaccumulation, and long-range transport, significantly threatening human health. The development of sensitive methods for nitro-PAH analysis in environmental samples is in great need. This study developed a novel carbonaceous SPME coating derived from metal-organic framework (MOF), namely a spherical assembly consisting of carbon nanorods with hierarchical porosity (HP-MOF-C), for the extraction and determination of nitro-PAHs in waters. The HP-MOF-C coated fiber demonstrated superior nitro-PAH extraction efficiencies, with enrichment factors 2∼70 times higher than commercial fibers. This enhancement was due to the strong hydrophobic, π-π electron coupling/stacking, and π-π electron donor-acceptor interactions between the carbonaceous framework of HP-MOF-C and the nitro-PAHs. Moreover, the unique hierarchical porous structure of HP-MOF-C accelerated the diffusion of nitro-PAHs, further facilitating their enrichment. The fiber also exhibited good thermal stability, remarkable chemical stabilities against common acid, base, and polar/non-polar solvents, and long service life (> 150 SPME cycles). The nitro-PAH determination method based on HP-MOF-C coating yielded wide linear ranges, low detection limits (0.4∼5.0 ng L-1), satisfactory repeatability and reproducibility, and good recoveries in real water samples. The proposed method was considered to be green according to the Analytical GREEnness assessment. The present study not only offers an efficient SPME coating for the enrichment of nitro-PAHs, but also provides insights into the design of porous coating materials.

Efficacy and safety of the modified Zhiwang decoction combined with methotrexate in early rheumatoid arthritis: study protocol for a randomised controlled trial.

INTRODUCTION: Rheumatoid arthritis (RA) is a progressive inflammatory autoimmune disease characterised by chronic systemic inflammation, which can cause swelling, stiffening and destruction of articular cartilage and bone. Early diagnosis and treatment of RA can improve outcomes and slow the progression of joint damage. Preliminary exploratory research had hinted an expected effect of modified Zhiwang decoction (MZWD) in treating early RA. However, few randomised clinical trials have evaluated the effectiveness of MZWD in early RA. Therefore, a parallel-group randomised controlled trial was designed to evaluate the efficacy and safety of MZWD combined with methotrexate (MTX) on early RA. METHODS AND ANALYSIS: This is a prospective, parallel-group, single-centre randomised controlled clinical study. A total of 150 patients will be randomly assigned to either the treatment (n=75) or control group (n=75). The treatment group will receive MZWD and MTX, and the control group will receive MTX for 12 weeks. The primary outcome of this study is Disease Activity Score-28, and the secondary outcomes are Fatigue Scale-14, Visual Analogue Scale pain scores and traditional Chinese medicine symptom scores. Safety outcomes, including adverse events and results of ECG and laboratory tests, will be monitored. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Clinical Research Ethics Committee of the China-Japan Friendship Hospital (no. 2022-KY-124) on 8 July 2022. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05508815).

Jolkinolide B ameliorates rheumatoid arthritis by regulating the JAK2/STAT3 signaling pathway.

BACKGROUND: Jolkinolide B (JB), an ent­abietane-type diterpenoid in Euphorbia plants, has various pharmacological activities, including anticancer, anti-inflammatory, and anti-tuberculosis activities. However, no previous studies have proven whether JB can be regarded as a targeted drug for the treatment of rheumatoid arthritis (RA). PURPOSE: This study aimed to evaluate the anti-RA effects of JB and explore the potential mechanisms. METHODS: Components and targets of JB and RA were identified in different databases, and potential targets and pathways were predicted by protein-protein interaction (PPI) network analysis and pathway enrichment analysis. Then, molecular docking and surface-plasmon resonance (SPR) were used to confirm the predict. The anti-arthritic effects of JB were studied in vivo with collagen-induced arthritis (CIA) rat model and in vitro with lipopolysaccharide (LPS) and interleukin-6 (IL-6)-induced RAW264.7 macrophage. Potential mechanisms were further verified by in vivo and in vitro experiments. RESULTS: The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that Th17 cell differentiation, prolactin signaling pathway, and JAK/STAT signaling pathway might be associated with anti-RA effects of JB. Molecular docking and SPR results showed that JB bound effectively to JAK2. JB significantly decreased body weight loss, arthritis index, paw thickness, and synovial thickness in CIA rats. Histomorphological results suggested the protective effects of JB on CIA rats with ankle joint injury. Molecular biology analysis indicated that JB suppressed the mRNA expression of inflammatory factors in ankle joints for CIA rats and reduced the concentration of these factors in LPS- induced RAW264.7 macrophage. The protein expression level of the JAK2/STAT3 pathway was also significantly decreased by JB. CONCLUSION: JB had a novel inhibitory effect on inflammation and bone destruction in CIA rats, and the mechanism might be related to the JAK2/STAT3 signaling pathway.

Integrated phytochemistry and network pharmacology analysis to reveal effective substances and mechanisms of Bushen Quhan Zhiwang decoction in the treatment of rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Quhan Zhiwang decoction (BQZD), a formula in traditional Chinese medicine (TCM), effectively delays bone destruction in rheumatoid arthritis (RA) patients. However, its chemical constituents, absorbed components, and metabolites remain unrevealed, and its mechanism in treating bone destruction in RA needs further investigation. AIM OF THE STUDY: Our objective is to identify the chemical constituents, absorbed components, and metabolites of BQZD and explore the potential mechanisms of BQZD in treating bone destruction in RA. MATERIALS AND METHODS: This study systematically identified the chemical constituents, absorbed components, and metabolites of BQZD using ultra-performance liquid chromatography with Q-Exactive Orbitrap mass spectrometry combined with parallel reaction monitoring. The absorbed components and metabolites were subjected to network pharmacology analysis to predict the potential mechanisms of BQZD in treating bone destruction in RA. The in vivo anti-osteoclastogenic and underlying mechanism were further verified in collagen-induced arthritis (CIA) rats. RESULTS: A total of 182 compounds were identified in BQZD, 27 of which were absorbed into plasma and organs and 42 metabolites were identified in plasma and organs. The KEGG analysis revealed that MAPK signaling pathway was highly prioritized. BQZD treatment attenuated paw swelling and the arthritis index; suppressed synovial hyperplasia, bone destruction, and osteoclast differentiation; and inhibited the levels of TNF-α, IL-1ß, and IL-6 in CIA rats. Mechanically, BQZD significantly decreased the protein expression levels of TRAF6, NFATc1, p-JNK, and p-p38, which might be related to 9 absorbed components and 1 metabolite. CONCLUSION: This study revealed the key active components and metabolites of BQZD. BQZD exhibits bone-protective effects via TRAF6/p38/JNK MAPK pathway, which may be associated with 9 absorbed components and 1 metabolite.

Methylation of T and B Lymphocytes in Autoimmune Rheumatic Diseases.

The role of abnormal epigenetic modifications, particularly DNA methylation, in the pathogenesis of autoimmune rheumatic diseases (ARDs) has garnered increasing attention. Lymphocyte dysfunction is a significant contributor to the pathogenesis of ARDs. Methylation is crucial for maintaining normal immune system function, and aberrant methylation can hinder lymphocyte differentiation, resulting in functional abnormalities that disrupt immune tolerance, leading to the excessive expression of inflammatory cytokines, thereby exacerbating the onset and progression of ARDs. Recent studies suggest that methylation-related factors have the potential to serve as biomarkers for monitoring the activity of ARDs. This review summarizes the current state of research on the impact of DNA and RNA methylation on the development, differentiation, and function of T and B cells and examines the progress of these epigenetic modifications in studies of six specific ARDs: systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, juvenile idiopathic arthritis, and ankylosing spondylitis. Additionally, we propose that exploring the interplay between RNA methylation and DNA methylation may represent a novel direction for understanding the pathogenesis of ARDs and developing novel treatment strategies.

Chemokines and lymphocyte homing in Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic systemic autoimmune disease that typically presents with lymphocyte, dendritic cell, and macrophage infiltration of exocrine gland ducts and the formation of ectopic germinal centers. The interactions of lymphocyte homing receptors and addressins and chemokines and their receptors, such as α4ß7/MAdCAM-1, LFA-1/ICAM-1, CXCL13/CXCR5, CCL25/CCR9, CX3CL1/CX3CR1, play important roles in the migration of inflammatory cells to the focal glands and the promotion of ectopic germinal center formation in SS. A variety of molecules have been shown to be involved in lymphocyte homing, including tumor necrosis factor-α, interferon (IFN)-α, IFN-ß, and B cell activating factor. This process mainly involves the Janus kinase-signal transducer and activator of transcription signaling pathway, lymphotoxin-ß receptor pathway, and nuclear factor-κB signaling pathway. These findings have led to the development of antibodies to cell adhesion molecules, antagonists of chemokines and their receptors, compounds interfering with chemokine receptor signaling, and gene therapies targeting chemokines and their receptors, providing new targets for the treatment of SS in humans. The aim of this study was to explore the relationship between lymphocyte homing and the pathogenesis of SS, and to provide a review of recent studies addressing lymphocyte homing in targeted therapy for SS.