Aberrant FcγRIIb and FcγRIII expression on monocytes from patients with Behçet's disease.

Behçet's disease (BD) patients have abnormal FcγR polymorphisms, the implication of which remains elusive. We examined FcγRIIb expression on neutrophils, monocytes, B cells, natural killer cells, dendritic cells and T cells, and FcγRI and FcγRIII expression on monocytes in BD patients and healthy controls using flow cytometry. We further stimulated monocytes with IgG and (or) lipopolysaccharide (LPS) and measured IL-6 and TNF-α production by enzyme-linked immunosorbent assay. We found that BD monocytes expressed a lower level of FcγRIIb and a higher level of FcγRIII, which were correlated with erythrocyte sedimentation rate and C-reactive protein and were rescued after treatment. Furthermore, LPS- and IgG-stimulated BD monocytes produced higher levels of IL-6 and TNF-α than HC monocytes. In summary, we found that BD monocytes downregulated FcγRIIb expression and upregulated FcγRIII expression, which were correlated with disease activity and potentially contributed to monocyte hyperactivation in BD.

Factors associated with health-related quality of life among family caregivers of people with Alzheimer's disease.

AIM: Based on the ageing population and the inadequate healthcare system in China, the majority of care for patients with Alzheimer's disease (AD) is provided by family caregivers. Caregivers suffer a long-term heavy care burden and pressure, which affects their physical and mental health. The present study aims at investigating health-related quality of life (HRQOL) among family caregivers of AD patients and exploring its influencing factors. METHODS: This study included 206 family caregivers (76 male, 130 female) of AD patients recruited from one Tier 3 hospital, one psychiatric hospital, two gerocomiums and three communities in Ganzhou city, Jiangxi Province, China. Measures included the World Health Organization (WHO) Quality of Life (WHO/ QOL-BREF) questionnaire, Zarit burden of care scale (ZBI), and social support rating scale (SSRS).We performed face-to-face or telephone interviews with patients and caregivers. The association between possible factors and changes in HRQOL was examined through stepwise multiple regression analysis. RESULTS: The majority of family caregivers felt moderate to severe level of burden. The average HRQOL score was 54.24 ± 10.36. The mean SSRS score was 30.4 ± 10.9. The average ZBI score was 41.2 ± 12.8. The HRQOL of family caregivers of AD patients was negatively correlated with the neuropsychiatric questionnaire score, ZBI score, and chronic diseases of caregivers (P < 0.05), and positively correlated with the SSRS score (P < 0.05). CONCLUSION: Reduced QOL was highly prevalent among AD patient family caregivers, and the level of burden, neuropsychiatric symptoms of patients, social support, and chronic diseases of caregivers were factors associated with HRQOL, and the effect of care burden is greatest. Interventions aimed at reducing the level of burden should focus not only on the patient but also on the caregiver.

T cell receptor ß repertoires as novel diagnostic markers for systemic lupus erythematosus and rheumatoid arthritis.

OBJECTIVE: T cell receptor (TCR) diversity determines the autoimmune responses in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and is closely associated with autoimmune diseases prognosis and prevention. However, the characteristics of variations in TCR diversity and their clinical significance is still unknown. Large series of patients must be studied in order to elucidate the effects of these variations. METHODS: Peripheral blood from 877 SLE patients, 206 RA patients and 439 healthy controls (HC) were amplified for the TCR repertoire and sequenced using a high-throughput sequencer. We have developed a statistical model to identify disease-associated TCR clones and diagnose autoimmune diseases. RESULTS: Significant differences were identified in variable (V), joining (J) and V-J pairing between the SLE or RA and HC groups. These differences can be utilised to discriminate the three groups with perfect accuracy (V: area under receiver operating curve > 0.99). One hundred ninety-eight SLE-associated and 53 RA-associated TCRs were identified and used for diseases classification by cross validation with high specificity and sensitivity. Disease-associated clones showed common features and high similarity between both autoimmune diseases. SLE displayed higher TCR heterogeneity than RA with several organ specific properties. Furthermore, the association between clonal expansion and the concentration of disease-associated clones with disease severity were identified, and pathogen-related TCRs were enriched in both diseases. CONCLUSIONS: These characteristics of the TCR repertoire, particularly the disease-associated clones, can potentially serve as biomarkers and provide novel insights for disease status and therapeutical targets in autoimmune diseases.

Evaluation of the Influence of Etiological Factors on the Economic Burden of Ischemic Stroke in Younger Patients in China Using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) Classification.

BACKGROUND Worldwide, stroke results in healthcare costs and economic costs, particularly in patients aged <45 years. This study aimed to evaluate the factors influencing the economic burden of ischemic stroke in younger patients in China based on the Trial of Org 10172 in Acute Stroke Treatment (TOAST) etiological classification. MATERIAL AND METHODS Retrospective review of the medical records of 961 patients aged between 18-45 years, diagnosed with acute ischemic stroke, was performed to identify healthcare costs for one year. Stroke severity was assessed using the modified Rankin Scale (mRS) score and the National Institutes of Health Stroke Scale (NIHSS) score. Stroke was categorized according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification as being due to large artery atherosclerosis (LAA), cardioembolism (CE), small artery occlusion (SAO), other determined causes (OC), and undetermined etiology (UND). RESULTS Total direct medical costs at one-year follow-up were US$10,954.14, including inpatient cost of US$5,958.44, and outpatient cost of US$3,397.60. Inpatient and total costs at one year were significantly increased in the CE subtype (P<0.001), and were significantly less in the UND subtype (P<0.001). Multivariable logistic regression analysis showed that mRS score, TOAST category, NIHSS score, and the presence of atrial fibrillation were the significant factors influencing cost at one-year follow-up and total cost in younger patients with ischemic stroke. Overall, patient costs in China were less than those in high-income countries. CONCLUSIONS In the younger patient population in China, etiological factors influenced the economic burden of ischemic stroke.

IFI44L promoter methylation as a blood biomarker for systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease with limited reliable diagnostic biomarkers. We investigated whether gene methylation could meet sensitivity and specificity criteria for a robust biomarker. METHODS: IFI44L promoter methylation was examined using DNA samples from a discovery set including 377 patients with SLE, 358 healthy controls (HCs) and 353 patients with rheumatoid arthritis (RA). Two independent sets including 1144 patients with SLE, 1350 HCs, 429 patients with RA and 199 patients with primary Sjögren's syndrome (pSS) were used for validation. RESULTS: Significant hypomethylation of two CpG sites within IFI44L promoter, Site1 (Chr1: 79 085 222) and Site2 (Chr1: 79 085 250; cg06872964), was identified in patients with SLE compared with HCs, patients with RA and patients with pSS. In a comparison between patients with SLE and HCs included in the first validation cohort, Site1 methylation had a sensitivity of 93.6% and a specificity of 96.8% at a cut-off methylation level of 75.5% and Site2 methylation had a sensitivity of 94.1% and a specificity of 98.2% at a cut-off methylation level of 25.5%. The IFI44L promoter methylation marker was also validated in an European-derived cohort. In addition, the methylation levels of Site1 and Site2 within IFI44L promoter were significantly lower in patients with SLE with renal damage than those without renal damage. Patients with SLE showed significantly increased methylation levels of Site1 and Site2 during remission compared with active stage. CONCLUSIONS: The methylation level of IFI44L promoter can distinguish patients with SLE from healthy persons and other autoimmune diseases, and is a highly sensitive and specific diagnostic marker for SLE.

Global burden, trends, and cross-country inequalities of urinary tract infections in adolescents and young adults, 1990-2019.

BACKGROUND: Limited studies have evaluated the global burden, trends, and cross-country inequalities for urinary tract infections (UTIs) in adolescents and young adults (AYAs). METHODS: Age-standardized rates (ASRs) of incidence (ASIR), mortality (ASMR) and Disability-Adjusted Life Years (DALYs) (ASDR) were used to describe the UTI burden. The estimated annual percentage changes (EAPCs) were calculated to evaluate the temporal trends from 1990 to 2019. The slope index of inequality and concentration index were utilized to quantify the distributive inequalities in the burden of UTIs. RESULTS: From 1990 to 2019, a significant increase in ASIR (EAPC=0.22%, 95% CI 0.19% to 0.26%) was found for UTIs in AYAs, and the increasing trend was more pronounced in males than females. Significant decreases in ASMR and ASDR were found for UTIs in females but not in males. The slope index of inequality changed from 21.80 DALYs per 100,000 in 1990 to 20.91 DALYs per 100,000 in 2019 for UTIs in AYAs. Moreover, the concentration index showed -0.23 in 1990 and -0.14 in 2019 for UTIs in AYAs. DISCUSSION: Countries with lower sociodemographic development levels shouldered a disproportionately higher burden of UTIs and should be targeted for strengthening their national programmes. CONCLUSIONS: UTIs remain an ongoing health burden for AYAs globally, with a substantial heterogeneity found across countries, sex, and age groups.

Imperatorin exerts antioxidant effects in vascular dementia via the Nrf2 signaling pathway.

Imperatorin, an active ingredient extracted from Angelica and Qianghuo, has anti-inflammatory, anti-oxidative stress damage, blocking calcium channels, and other properties. Our preliminary findings revealed the protective role of imperatorin in the treatment of vascular dementia, we further explored the underlying mechanisms concerning the neuroprotection function of imperatorin in vascular dementia. The cobalt chloride (COCl2)-induced chemical hypoxia and hypoglycemia of hippocampal neuronal cells was applied as in vitro vascular dementia model. Primary neuronal cells was isolated from the hippocampal tissue of SD suckling rats within 24 h of birth. Hippocampal neurons were identified by immunofluorescence staining of microtubule-associated protein 2. Silencing or overexpression of Nrf2 was conducted by transfection of corresponding plasmids in hippocampal neuronal cells. Cell viability was detected by MTT assay to determine the optimal modeling concentration of CoCl2. Mitochondrial membrane potential, intracellular reactive oxygen species and apoptosis rate was measured by flow cytometry. The expression of anti-oxidative proteins was detected by quantitative real-time PCR and western blot, including Nrf2, NQO-1 and HO-1. Nrf2 nuclear translocation was detected using laser confocal microscopy. The modeling concentration of CoCl2 was 150umol/l, and the best interventional concentration of imperatorin was 7.5umol/l. Significantly, imperatorin facilitated the nuclear localization of Nrf2, promoted the expressions of Nrf2, NQO-1, and HO-1 relative to the model-control group. Moreover, imperatorin reduced the mitochondrial membrane potential and ameliorated CoCl2-induced hypoxic apoptosis in hippocampal neurons. On the contrary, silencing Nrf2 completely abrogated the protective effects of imperatorin. Imperatorin might be an effective drug for preventing and treating vascular dementia.

A taxonomic revision of the subfamily Myzininae from China, with a key to the Chinese species (Hymenoptera: Tiphiidae).

In this study, a total of 11 species belonging to four genera of Myzininae are recorded from China, among which a new species, namely Hylomesa punctata sp. nov. is described from Tibet and Yunnan, and four species are newly recorded. All the species are illustrated and a key to them is provided in this paper.

Efficacy and safety of HLX01 in patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy: a phase 3 study.

BACKGROUND: To evaluate the efficacy and safety of HLX01, a rituximab biosimilar, as combination therapy with methotrexate in Chinese patients with active rheumatoid arthritis who had inadequate responses to methotrexate. METHODS: In this double-blind, placebo-controlled phase 3 trial, biologic-naïve patients with moderate-to-severe active rheumatoid arthritis and inadequate responses to methotrexate were randomized 2:1 to receive 1000 mg HLX01 or placebo intravenously on days 1 and 15. On the first day of weeks 24 and 26, patients in both groups received 1000 mg HLX01 via intravenous infusion. The primary endpoint was the American College of Rheumatology (ACR) 20 response rate at week 24. Secondary endpoints including efficacy, safety, immunogenicity, pharmacokinetics and pharmacodynamics were assessed up to week 48. RESULTS: Between 28 May 2018 and 11 September 2020, 275 patients were randomized to the HLX01 group (n = 183) or the placebo group (n = 92). At week 24, the proportion of patients achieving ACR20 response was significantly greater in the HLX01 group compared with the placebo group in the intention-to-treat population (60.7% vs 35.9%; P < 0.001) and per-protocol set (60.3% vs 37.1%; P < 0.001). Most secondary efficacy endpoints favoured HLX01 when assessed at weeks 12, 24, 36 and 48. Incidences of treatment-emergent adverse events were similar between groups. Infusion-related reactions occurred more frequently following the initial two doses of HLX01 than the subsequent doses. CONCLUSIONS: HLX01 plus methotrexate improved clinical outcomes compared with placebo in Chinese patients with rheumatoid arthritis who had inadequate responses to methotrexate. This treatment regimen was well tolerated, showing comparable safety profiles to placebo. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03522415 . Registered on 11 May 2018.

Effects of imperatorin on apoptosis and synaptic plasticity in vascular dementia rats.

In view of the complicated pathophysiological process of vascular dementia (VD), drugs for the clinical treatment of VD mainly target related risk factors, while drugs with excellent efficacy in cognitive function are still relatively lacking. Imperatorin (IMP), an active constituent extracted from angelica dahuricae and notopterygium Notopterygii, which has anti-inflammatory, vasodilator, anticoagulant, block calcium channel, anticonvulsant, and anti oxygen free radical injury properties. Therefore,the present study examined its effects on VD rats and the underlying molecular mechanisms, in order to provide promising therapeutic methods. VD was established by modified ligation of perpetual two-vessel occlusion (2VO). After 2VO surgery, IMP (2.5, 5, and 10 mg/kg) was administered by intraperitoneal injection for 12 consecutive weeks to evaluate therapeutic effects. Cognitive function was verified by the Morris water maze. The neuronal morphological changes were examined via Hematoxylin-Eosin staining. Real-Time PCR and Western blot were used for detecting pro- and antiapoptotic biomarkers, and the hippocampus synaptic damage was examined by Transmission electron microscope. We revealed that 2VO-induced cognitive impairment, hippocampus CA1 neuron damage, apoptosis and synaptic damage. IMP-treatment significantly improved 2VO-induced cognitive deficits and hippocampus neuron damage. Molecular analysis revealed that IMP inhibited apoptosis through the down regulation of Bax, Caspase-3 and upregulation of Bcl-2. Meanwhile, IMP-treatment markedly improved synaptic ultrastructure morphology, increased the SAZ length, PSD thickness and up-regulated PSD-95 expression. Collectively, our findings demonstrated that IMP was effective in the treatment of 2VO-induced VD via inhibiting apoptosis of hippocampus neurons and reducing the synaptic plasticity destroy.

Expression of circular RNAs in the vascular dementia rats.

PURPOSE: Circular RNAs (circRNAs) are a class of endogenous noncoding RNA molecules that lack free 5' and a 3' end poly(A) tail. CircRNAs are enriched in neural tissues, and have been found to be associated with various diseases of the central nervous system. This study aimed to examine key circRNAs involved in vascular dementia(VD) model rats. METHODS: Total RNA-seq profiles of hippocampus samples from normal and vascular dementia rats were extracted and high throughput sequencing was performed. Quantitative real-time polymerase chain reaction (qPCR) was used to confirm the circRNA expression profiles. Differential expression of circRNA has been used for analysis via the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The circRNA-miRNA-mRNA network was then constructed. RESULTS: The data of high-throughput sequencing showed that there were 425 circRNAs differentially expressed between VD and normal rats (fold change (FC)≥2.0 and p-value< 0.05). In the VD group, a total of 237 were significantly upwardly revised, while the other 188 were downwardly revised. Eleven of these expressed more than 10 times in the VD model rats. The Expression levels of 10 circRNAs (circ_Map2k5, circ_Ulk2, circ_Plekha5, circ_Plcl1, circ_Sntg1, circ_Morc3, circ_Rims1, circ_ Stxbp5l, circ_ Agtpbp1, circ_Lrrc28) were verified by qPCR, which were persistent with RNA-seq data(P < 0.05). GO analysis indicated that majority of predicted target genes were involved in biological processes, such as cellular processes, nervous system development, etc. Cellular component, such as cellular parts, intracellular parts, cytoplasm and molecular function, such as binding, catalytic activity, etc. Moreover, KEGG analysis showed that many genes were enriched in cholinergic synapses, the MAPK signaling pathways, GABAergic synapses, metabolic pathways, the mTOR signaling pathways, and so on. CONCLUSIONS: Our results suggest the involvement of different ncRNA expression patterns in the pathogenesis (are associated with the pathogenesis of VD. Our findings provide a novel perspective for further research into potential mechanisms of VD and might facilitate the development of novel therapeutics targeting ncRNAs.

Malus hupehensis leaves extract attenuates obesity, inflammation, and dyslipidemia by modulating lipid metabolism and oxidative stress in high-fat diet-induced obese mice.

Malus hupehensis leaves (MHL) are used to make traditional Chinese tea. In this study, MHL extract was shown to improve metabolic disorders and inflammatory response in high-fat diet-induced obese mice. MHL extract could reduce body weight, and significantly alleviate liver damage and fat accumulation. MHL extract caused a decrease in the levels of ALT, AST, AKP, TC, TG, LDL-C, and an increase in the level of HDL-C. It also caused a decrease in inflammatory cytokines, including TNF-α, IFN-γ, IL-1ß, IL-6, and an increase in the anti-inflammatory cytokine IL-10 and IL-4. MHL extract could upregulate mRNA expression of PPAR-α, LPL, CPT1, CYP7A1, SOD1, SOD2, CAT, GSH1, and GSH-Px and downregulate that of PPAR-γ and C/EBP-α in the liver of obese mice. In conclusion, our work represents the first study demonstrating that MHL extract possesses an anti-obesity effect and alleviates obesity-related symptoms, including dyslipidemia, chronic low-grade inflammatory, and liver damage. PRACTICAL APPLICATIONS: The research may contribute to the development and application of MHL as functional foods or dietary supplement to fight against obesity.

Anti-fibrotic effects of pirfenidone by interference with the hedgehog signalling pathway in patients with systemic sclerosis-associated interstitial lung disease.

AIM: To determine whether pirfenidone attenuates lung fibrosis by interfering with the hedgehog (Hh) signalling pathway in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). METHODS: Twenty-five SSc-ILD patients (20 first visit, five who underwent pirfenidone treatment for 6 months) and 10 healthy controls were recruited. Lung tissues were obtained by open-chest surgery, and primary lung fibroblasts were isolated, cultured and stimulated with pirfenidone. The levels of the proteins glioma-associated oncogene 1 (GLI1), suppressor of fused (Sufu), α-smooth muscle actin, and fibronectin in lung tissues or fibroblasts were determined by Western blotting. The messenger RNA levels of GLI1, glioma-associated oncogene 2, protein patched homolog 1, and Sufu in lung tissues or fibroblasts were determined by quantitative reverse-transcription polymerase chain reaction. Meanwhile, the levels of phosphorylation glycogen synthase kinasep-3ß (pGSK-3ß), phosphorylation SMAD2 (pSMAD2), and phosphorylation c-Jun N-terminal kinase (pJNK) in fibroblasts were determined by Western blotting. RESULTS: Hh pathway activation was increased in the lung tissue of SSc-ILD patients and was decreased by pirfenidone, Sufu was upregulated in lung fibroblasts isolated from SSc-ILD patients after pirfenidone challenge, and pirfenidone inhibited the phosphorylation of GSK-3ß signalling. CONCLUSION: Pirfenidone has anti-fibrotic effects in SSc-ILD patients by interfering with both the Hh signalling pathway and the GSK-3ß signalling pathway via the regulation of Sufu expression. These results might promote its use in other Hh driven lung diseases such as idiopathic pulmonary fibrosis and especially the interstitial lung disease associated with connective tissue diseases.

Comparison of the impact of Tripterygium wilfordii Hook F and Methotrexate treatment on radiological progression in active rheumatoid arthritis: 2-year follow up of a randomized, non-blinded, controlled study.

BACKGROUND: Tripterygium wilfordii Hook F (TwHF) alone or in combination with methotrexate (MTX) has been shown to be more effective than MTX monotherapy in controlling the manifestations in subjects with disease-modifying antirheumatic drug (DMARD)-naïve active rheumatoid arthritis (RA) over a 6-month period. The long-term impact of these therapies on disease activity and radiographic progression in RA has not been examined. METHODS: Patients with DMARD-naïve RA enrolled in the "Comparison of Tripterygium wilfordii Hook F with methotrexate in the Treatment of Active Rheumatoid Arthritis" (TRIFRA) study were randomly allocated into three arms with TwHF or MTX or the two in combination. Clinical indexes and radiographic data at baseline and year 2 was collected and compared using an intent-to-treat (ITT) and a per-protocol (PP) analysis. Two radiologists blinded to the treatment scored the images independently. RESULTS: Of 207 subjects 109 completed the 2-year follow up. The number of subjects withdrawing from the study and the number adhering to the initial regimens were similar among the three groups (p > = 0.05). In the ITT analysis, proportions of patients reaching American College of Rheumatology 50% (ACR50) response criteria were 46.4%, 58.0% and 50.7% in the MTX, TwHF and MTX + TwHF groups (TwHF vs MTX monotherapy, p = 0.004). Similar patterns were found in ACR20, ACR70, Clinical Disease Activity Index good responses, European League Against Rheumatism good response, remission rate and low disease activity rate at year 2. The results of the PP analysis agreed with those in the ITT analysis. The changes in total Sharp scores and joint erosion and joint space narrowing during the 2 years were associated with changes in disease activity measured by the 28-joint count Disease Activity Score and were comparable among the three groups (p > 0.05). Adverse events were similar in the three treatment groups. CONCLUSIONS: During the 2-year therapy period, TwHF monotherapy was not inferior to MTX monotherapy in controlling disease activity and retarding radiological progression in patients with active RA. TRIAL REGISTRATION: This is a follow-up study. Original trial registration: ClinicalTrials.gov , NCT01613079 . Registered on 4 June 2012.

Metabolic status and personality affect the prognosis of patients with continuous ambulatory peritoneal dialysis.

Continuous ambulatory peritoneal dialysis (CAPD) is recognized as an effective and economical therapy for end-stage renal disease (ESRD). However, the drop-out and mortality rates of this treatment remain high. The aim of the present study was to investigate the potential effects of metabolic status and personality on the prognosis of ESRD patients receiving CAPD. A total of 835 patients (455 men and 380 women) were enrolled in the cross-sectional survey. Analysis of variance and Spearman correlations were used to analyze variables in two groups of ESRD patients: group L (dialysis duration < 3 years) and group H (dialysis duration ≥ 3 years). The variables included gender, age, duration of dialysis, primary diseases, blood pressure, body mass index (BMI), hemoglobin (Hb), serum albumin, Subjective Global Assessment (SGA), blood lipids, fasting blood glucose, renal function, immunoreactive parathyroid hormone (iPTH), serum phosphorus and calcium, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Kt/V, and Life Orientation Test-Revised (LOT-R) scores. Levels of DBP, BUN, glucose, CRP, SBP, SGA, TG, LDL, creatinine, iPTH, ESR, and LOT-R scores were significantly higher in group H than in Group L, whereas Hb and Kt/V were significantly lower in group H. The dialysis duration was positively correlated with the blood pressure, SGA scores, TG, LDL, PTH, CRP, and LOT-R scores, but negatively correlated with Kt/V. Our results suggest that hypertension, anemia, hypoproteinemia, SGA, TG, LDL, iPTH, CRP, Kt/V, and personalities are potentially important factors affecting the prognosis of ERSD patients with CAPD.

Value of ultrasonography for diagnosis of synovitis associated with rheumatoid arthritis.

AIM: To investigate the value of ultrasonography (US) for diagnosing synovitis associated with rheumatoid arthritis (RA). METHOD: Bilateral metacarpophalangeal (MCP), proximal interphalangeal (PIP) II-V and wrist joints of 46 RA patients and 35 healthy controls were evaluated by quantitative and semiquantitative US. Wrists on more severely affected sides of 20 of the 46 patients also underwent magnetic resonance imaging (MRI). The MRI and US results were compared. The US cutoff to distinguish pathology was calculated. The two US methods were compared and the correlation between quantitative methods and clinical serologic markers was analyzed. RESULTS: The imaging techniques (US and MRI) for detecting synovitis produced consistent results (γ = 0.70-0.77, P < 0.001). When the cutoffs for the MCP and PIP joints were 2.5 and 2.6 mm, respectively; the sensitivities/specificities were 82.8%/85.8% and 98.2%/84.8%, respectively. When the cutoff for the wrist was 5.2 mm, the sensitivity/specificity was 93.4%/93.4%. The average synovial membrane thickness was positively related to biochemical markers erythrocyte sedimentation rate, C-reactive protein, anticyclic citrullinated peptide antibody, and Disease Activity Index of 28 joints (γ = 0.307-0.614; P = 0.020, 0.038, 0.01, < 0.001, respectively) but was poorly related to rheumatoid factor immunoglobulin A (RF-IgA), RF-IgM, and RF-IgG (γ = 0.06-0.115; P = 0.45, 0.45, 0.62, respectively). CONCLUSIONS: US is a valid method for diagnosing early-stage synovitis, with high-accuracy cutoffs for MCP, PIP and wrist joints set at 2.5, 2.6 and 5.2 mm. The mean synovial thicknesses of the bilateral wrist, MCP II-IV and PIP II-IV joints can be used to assess disease activity.