Proteomic analysis of neonatal mouse hearts shows PKA functions as a cardiomyocyte replication regulator.

The ability of the adult mammalian heart to regenerate can save the cardiac muscle from a loss of function caused by injury. Cardiomyocyte regeneration is a key aspect of research for the treatment of cardiovascular diseases. The mouse heart shows temporary regeneration in the first week after birth; thus, the newborn mouse heart is an ideal model to study heart muscle regeneration. In this study, proteomic analysis was used to investigate the differences in protein expression in the hearts of neonatal mice at days 1 (P1 group), 4 (P4 group), and 7 (P7 group). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed changes in several groups of proteins, including the protein kinase A (PKA) signaling pathway. Moreover, it was found that PKA inhibitors and agonists regulated cardiomyocyte replication in neonatal mouse hearts. These findings suggest that PKA may be a target for the regulation of the cardiomyocyte cell cycle.

Interstitial lung disease in Primary Sjögren's syndrome.

BACKGROUND: Interstitial lung disease (ILD) may cause life-threatening complications of primary Sjogren's syndrome (pSS), and has a poor prognosis in terms of survival and quality of life. To date, few studies have investigated the risk factors for ILD detected by high-resolution computed tomography (HRCT) in pSS patients with or without respiratory symptoms. METHODS: Data of 333 patients with newly diagnosed pSS were retrospectively analysed. Interstitial lung disease involvement was defined as typical abnormalities on HRCT and/or pulmonary function tests. Multivariate regression model was used to evaluate the association between interstitial lung disease and pSS characteristics. RESULTS: Sixty-six patients (19.82%) were diagnosed with pSS-ILD. Ground glass opacities (87.88%) and septal/sub pleural lines (81.82%) were most frequent. Based on pulmonary high-resolution computed tomography, patients were divided into nonspecific (n = 42), usual (n = 20), lymphocytic interstitial pneumonia (n = 3) and cryptogenic organising pneumonia (n = 1) groups. There was a strong association between erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) and the HRCT-score. Pulmonary function tests revealed impaired diffusion capacity for carbon monoxide and total lung capacity, and coexistence of small airway lesions in pSS-interstitial lung disease. On logistic regression analysis, age, Raynaud's phenomenon, lymphopenia, cough, dyspnoea and rampant dental caries were risk factors associated with pSS-interstitial lung disease. CONCLUSIONS: Interstitial lung disease involvement in pSS is a common clinical occurrence. The clinical manifestation is nonspecific and variable; Raynaud's phenomenon and lymphopenia may predict its onset. pSS patients with advanced age, dry cough and dyspnoea should be systematically evaluated for ILD involvement and managed according to their symptoms.

Targeting NFATc4 attenuates non-alcoholic steatohepatitis in mice.

BACKGROUND & AIMS: The nuclear factor of activated T-cells (NFAT) family was first recognised to play an important role in the differentiation of T cells, but has since been shown to regulate multiple pathophysiological processes. However, whether it is involved in the pathogenesis of non-alcoholic steatohepatitis (NASH) remains unknown. METHODS: Hepatic NFATc expression and localisation were analysed in C57BL/6 mice on a methionine-choline-deficient diet, as well as in samples from non-alcoholic fatty liver disease patients. Gain- or loss-of-function approaches were used to investigate the role of NFATc4 in NASH. RESULTS: NFATc4 translocates from the cytoplasm to the nucleus in hepatocytes of both humans and rodents with NASH. NFATc4 knockdown resulted in decreased hepatic steatosis, inflammation, and fibrosis during NASH progression. Mechanistically, we found that activated NFATc4 directly bound to peroxisome proliferator-activated receptor α (PPARα) in the nucleus and negatively regulated its transcriptional activity, thereby impairing the hepatic fatty acid oxidation pathway and increasing lipid deposition in the liver. Moreover, NFATc4 activation increased the production and secretion of osteopontin (OPN) from hepatocytes, which subsequently enhanced the macrophage-mediated inflammatory response and hepatic stellate cell-mediated fibrosis progression via paracrine signalling. CONCLUSIONS: Hepatic NFATc4 activation accelerates the progression of NASH by suppressing PPARα signalling and increasing OPN expression. Genetic or pharmacological inhibition of NFATc4 may have potential for future therapy of NASH. LAY SUMMARY: NFATc4 is activated in the non-alcoholic steatohepatitis of mice and patients. Inhibition of NFATc4 activation alleviates lipid deposition, inflammatory response, and fibrosis progression in the liver.

Role of adipokine zinc-α2-glycoprotein in coronary heart disease.

Zinc-α2-glycoprotein (AZGP1) is a newly identified adipokine that is associated with lipid metabolism and vascular fibrosis. Although adipokines contribute to lipid dysfunction and its related diseases, including stroke and coronary heart disease (CHD), the role of AZGP1 remains unclear. In this study, the role of AZGP1 in atherosclerosis and CHD was investigated. Serum AZGP1 levels from control (n = 84) and CHD (n = 91) patients were examined by ELISA and its relationship with various clinical parameters was analyzed. Immunohistochemistry and immunofluorescence were used to detect the expression of AZGP1 and its receptor in coronary atherosclerotic arteries. THP-1 and human embryonic kidney 293 cells were used to verify its anti-inflammatory role in atherosclerosis. Serum AZGP1 levels in CHD patients were lower than controls (P < 0.01) and independently associated with CHD prevalence (P = 0.021). AZGP1 levels also inversely correlated with the Gensini score. Immunohistochemistry and immunofluorescence showed that AZGP1 and its receptor ß3-adrenoceptor (ß3-AR) colocalized in lipid-rich areas of atherosclerotic plaques, particularly around macrophages. In vitro, AZGP1 had no effect on foam cell formation but showed anti-inflammatory effects through its regulation of JNK/AP-1 signaling. In summary, AZGP1 is an anti-inflammatory agent that can be targeted for CHD treatment.

Visfatin Level and The Risk of Hypertension and Cerebrovascular Accident: A Systematic Review and Meta-Analysis.

High blood pressure is related with increased cerebrovascular accident. High visfatin / NAMPT(nicotinamide phosphoribosyltransferase) plasma levels may promote vascular inflammation and atherosclerotic plaque destabilization and have been evaluated as a marker for identifying stages of essential hypertension. However, its role in the pathogenesis of hypertension and cerebrovascular accident (CVA) is still uncertain. In order to review and meta-analyze observational studies investigating visfatin concentration and the risk for hypertension or CVA, a systematic search of PubMed, ovid EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) until December 07, 2016 was performed. After data extraction and quality assessment, a meta-analysis was performed using RevMan 5.3 and STATA 14.0. A total of 1693 adults from 8 studies for hypertension (974 with hypertension) and 1696 adults from 7 CVA studies (957 with CVA) were enrolled in the current meta-analysis. Cochran's Q-statistic and I2 test were applied to estimate the heterogeneity of the studies. The fixed-effects were used to compute the weighted mean difference in visfatin levels. Plasma visfatin concentration was much higher in hypertension and CVA patients than in healthy individuals. These evidences suggested the association of hypertension and CVA with higher plasma visfatin level.

Efficacy and safety of iron supplementation in patients with heart failure and iron deficiency: a meta-analysis.

Fe therapy can be effective in heart failure patients both with and without anaemia. However, the role of Fe therapy in such patients is still uncertain. In this review, the aim was to evaluate the efficacy and safety of Fe therapy in adult patients with heart failure who have reduced ejection fraction (HFrEF). Multiple databases (PubMed, Medline, EMBASE, the Cochrane Library and Clinical Trials) were searched up to December 2017 and the reference lists of relevant articles obtained from the search were reviewed. Data extracted from randomised control trials (RCT) selected for the review were pooled using a fixed effects model or a random effects model, according to heterogeneity between trials. Nine RCT were included in this meta-analysis which included a total of 789 patients who received Fe therapy and who in turn were compared with 585 controls. There was significant improvement in the 6-min walk test (19·05 m, 95 % CI 10·48, 27·62) and peak VO2/kg (0·93 ml/kg per min, 95 % CI 0·16, 1·69) in the Fe supplementation arm. With Fe therapy, fewer patients were hospitalised for heart failure (OR: 0·42, 95 % CI 0·27, 0·65), but no relationship was found for total re-hospitalisation (OR: 0·70, 95 % CI 0·32, 1·51) or mortality (OR: 0·70, 95 % CI 0·38, 1·28). Fe therapy has the potential to improve exercise tolerance, reduce re-hospitalisations for patients with HFrEF having Fe deficiency. In addition, Fe supplementation was found to be safe, with no increased rate of adverse events.

PARP1-mediated PPARα poly(ADP-ribosyl)ation suppresses fatty acid oxidation in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: PARP1 is a key mediator of cellular stress responses and critical in multiple physiological and pathophysiological processes of cells. However, whether it is involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) remains elusive. METHODS: We analysed PARP1 activity in the liver of mice on a high fat diet (HFD), and samples from NAFLD patients. Gain- or loss-of-function approaches were used to investigate the roles and mechanisms of hepatic PARP1 in the pathogenesis of NAFLD. RESULTS: PARP1 is activated in fatty liver of HFD-fed mice. Pharmacological or genetic manipulations of PARP1 are sufficient to alter the HFD-induced hepatic steatosis and inflammation. Mechanistically we identified peroxisome proliferator-activated receptor α (PPARα) as a substrate of PARP1-mediated poly(ADP-ribosyl)ation. This poly(ADP-ribosyl)ation of PPARα inhibits its recruitment to target gene promoters and its interaction with SIRT1, a key regulator of PPARα signaling, resulting in suppression of fatty acid oxidation upregulation induced by fatty acids. Moreover, we show that PARP1 is a transcriptional repressor of PPARα gene in human hepatocytes, and its activation suppresses the ligand (fenofibrate)-induced PPARα transactivation and target gene expression. Importantly we demonstrate that liver biopsies of NAFLD patients display robust increases in PARP activity and PPARα poly(ADP-ribosyl)ation levels. CONCLUSIONS: Our data indicate that PARP1 is activated in fatty liver, which prevents maximal activation of fatty acid oxidation by suppressing PPARα signaling. Pharmacological inhibition of PARP1 may alleviate PPARα suppression and therefore have therapeutic potential for NAFLD. LAY SUMMARY: PARP1 is activated in the non-alcoholic fatty liver of mice and patients. Inhibition of PARP1 activation alleviates lipid accumulation and inflammation in fatty liver of mice.

Inhibition of Poly(ADP-Ribose) Polymerase-1 Protects Chronic Alcoholic Liver Injury.

Activation of Kupffer cells (KCs) by gut-derived endotoxin plays a pivotal role in the pathogenesis of alcoholic liver diseases (ALD). Limiting the activation of resident KCs attenuates chronic ethanol-induced liver steatosis and injury. Poly (ADP-ribose) polymerase (PARP)-1 is suggested to play a role in a number of chronic inflammatory diseases. In this study, we found a significant increase of hepatic PARP activity in mice with short-term and long-term ethanol-induced ALD. Male mice on a long-term ethanol diet exhibited severe hepatic steatosis and apoptosis and enhanced KC activation and neutrophil infiltration. However, pharmacologic inhibition of PARP activity or genetic depletion of PARP1 significantly attenuated these detrimental effects in vivo. We found that inhibition of PARP1 effectively reduced hepatic expression of genes involved in lipogenesis and elevated hepatic expression of genes involved in lipolysis. Moreover, limited KC activation and neutrophil infiltration were observed in PARP1 knockout mice or PARP inhibitor-treated mice. Furthermore, in vitro experiments found that LPS-induced macrophage activation was limited by PARP inhibitor, and exposure of ethanol-treated hepatocytes to this conditioned medium further decreased the number of apoptotic and steatotic cells. Taken together, these findings suggest that PARP1 inhibition protects against long-term ethanol-induced liver injury, as indicated by limited hepatocytes steatosis, apoptosis, inflammation levels, and neutrophil infiltration, mainly by limiting KC activation during the initiation of ALD.

The impact of rheumatoid arthritis on work capacity in Chinese patients: a cross-sectional study.

OBJECTIVE: To evaluate the impact of RA on work capacity and identify factors related to work capacity impairment in patients with RA. METHODS: A cross-sectional multicentre study was performed in 21 tertiary care hospitals across China. A consecutive sample of 846 patients with RA was recruited, of which 589 patients of working age at disease onset constituted the study population. Information on the socio-demographic, clinical, working and financial conditions of the patients was collected. Logistic regression analyses were used to identify factors associated with work capacity impairment. RESULTS: The rate of work capacity impairment was 48.0% in RA patients with a mean disease duration of 60 months (interquartile range 14-134 months), including 11.7% leaving the labour force early, 33.6% working reduced hours and 2.7% changing job. Multivariable logistic regression analysis showed that reduced working hours was significantly related to current smoking [odds ratio (OR) 2.07 (95% CI 1.08, 3.97)], no insurance [OR 1.94 (95% CI 1.20, 3.12)], in manual labour [OR 2.66 (95% CI 1.68, 4.20)] and higher HAQ score [OR 2.22 (95% CI 1.36, 3.60)]. There was an association of current smoking [OR 3.75 (95% CI 1.54, 9.15)], in manual labour [OR 2.33 (95% CI 1.17, 4.64)], longer disease duration [OR 1.01 (95% CI 1.00, 1.01)] and lower BMI [OR 0.90 (95% CI 0.82, 0.99)] with leaving the labour force early. CONCLUSION: There is a substantial impact of RA on the work capacity of patients in China. Social-demographic, disease- and work-related factors are all associated with work capacity impairment.

Poly(ADP-ribose) polymerase 1 is a key regulator of estrogen receptor α-dependent gene transcription.

Activation of nuclear receptor estrogen receptor α (ERα) exerts cardiovascular protective effects by modulating the expression of ERα target genes. However, the underlying mechanism remains unclear. PARP1 is a ubiquitous multifunctional nuclear enzyme. In this study, we examined the interplay between PARP1 and ERα, and identified PARP1 as an important regulator of ERα-dependent transcription. We showed that PARP1 could directly bind to ERα, and ERα could be poly(ADP-ribosyl)ated by PARP1. Poly(ADP-ribosyl)ation increased ERα binding to estrogen response element (ERE) present in the promoter of target genes and promoted ERα-mediated gene transcription. Estradiol, the ligand of ERα, increased PARP enzymatic activity and enhanced poly(ADP-ribosyl)ation of ERα. Upon treatment with estradiol, ERα binding to ERE- and ERα-dependent gene expression was dramatically increased in cultured vascular smooth muscle cells (VSMCs). Inhibition of PARP1 by PARP inhibitor or PARP1 siRNA decreased ERα binding to ERE and prevented ERα-dependent gene transcription in VSMCs. Further studies revealed that PARP1 served as an indispensible component for the formation of the ERα-ERE complex by directly interacting with ERα. Thus, our results identify PARP1 as a key regulator of ERα in controlling ERα transactivation.

A randomized, double-blind, and placebo-controlled multicenter clinical trial of a novel cytotoxic T-lymphocyte antigen-4 fusion protein, Leining, in Chinese active rheumatoid arthritis patients with an inadequate response to methotrexate.

To assess the clinical efficacy as well as safety profiles of Leining, a novel cytotoxic T-lymphocyte antigen-4 fusion protein, versus placebo in the treatment of Chinese active rheumatoid arthritis (RA) patients with an inadequate clinical response to methotrexate (MTX). In this 24-week, randomized, double-blind, placebo-controlled multicenter study, a total of 440 Chinese patients with active RA with an inadequate response to MTX were randomly assigned to receive Leining (10 mg/kg) or placebo. Clinical response was assessed using the American College of Rheumatology 20 % improvement criteria ACR20, ACR50, and ACR70, with ACR20 as the primary major endpoints. Disease activity scores in 28 joints with erythrocyte sedimentation rate assessment (DAS28-ESR) were used to evaluate disease activity. After 24 weeks of treatment, significantly more patients in Leining group achieved ACR20 response than those in placebo group (70.61 vs. 46.36 %; p < 0.001). Similarly, ACR50 and ACR70 responses of Leining group were significantly higher than those of placebo group (40.30 vs. 22.73 %; p < 0.001 and 16.67 vs. 7.27 %; p < 0.05, respectively). DAS28-ESR in Leining group was significantly reduced compared to that in placebo group, with greater clinically meaningful (>1.2 unit) improvement (54.85 vs. 29.09 %, p < 0.05). Both the rates of remission (DAS28-ESR < 2.6) and low disease activity (DAS28-ESR < 3.2) were greater in the Leining group than those in the placebo group (12.42 vs. 2.73 %; p < 0.05 and 15.45 vs. 2.73 %; p < 0.05 respectively). The overall incidence of adverse events was similar in both Leining and placebo groups. No neutralizing antibodies were detected. Leining demonstrated clinically meaningful efficacy compared with placebo in Chinese patients with active RA despite MTX therapy. Administration of Leining in combination with MTX for 24 weeks was well tolerated.

Thymic stromal lymphopoietin over-expressed in human atherosclerosis: potential role in Th17 differentiation.

BACKGROUND: Adaptive immunity plays a critical role in atherosclerosis and T helper 17 (Th17) cells, a new T-cell lineage, are recently reported to be involved in atherosclerosis. However, the mechanism underlying Th17 inflammation in atherosclerosis remains largely unknown. Thymic stromal lymphopoietin (TSLP) is a novel IL-7-like cytokine and mainly responsible for Th2 inflammation in many inflammatory diseases. METHODS AND RESULTS: Immunohistochemistry showed that TSLP over-expressed in human atherosclerotic lesion and could be induced by ox-LDL in human vascular smooth muscle cells (HVSMCs) and human umbilical vein endothelial cells (HUVECs). TSLP, in turn, could activate dendritic cells (DCs) to differentiate Th17 inflammation in naive CD4(+) T cells. CONCLUSION: TSLP induced by ox-LDL could promote Th17 immune response in vitro, which may be implicated in Th17 inflammation in atherosclerosis.

Kruppel-like factor 2 regulates dendritic cell activation in patients with acute coronary syndrome.

OBJECTIVE: Dendritic cells (DCs) activation is important in atherosclerosis and coronary heart disease, but the mechanisms regulating activation of dendritic cells remain largely unclear. The aim of this study was to evaluate the effect of transcription factor Kruppel-like factor 2 (KLF2) in the proinflammatory activation of DCs in acute coronary syndrome. METHODS AND RESULTS: In this study, the expression of CD80 and KLF2 was detected in DCs in normal health controls, patients with stable angina (SA), and acute coronary syndrome (ACS). Our study found that compared with normal control and SA, KLF2 expression in DCs is reduced in patients with ACS. Moreover, the surface expression of CD80 was increased in ACS. In vitro experiment, we found that ox-LDL could increase CD80 expression and decrease KLF2 expression. Furthermore, down-regulated KLF2 could in turn increase CD80 expression via NF-κB pathway. CONCLUSIONS: These observations identify KLF2 as a novel negative regulator of DC function and it may play an essential role in DC activation in ACS.

A rare concomitance of Wilson's disease and systemic lupus erythematosus in a teenage girl: a case report and literature review.

Background: Wilson's disease (WD) is an inherited disorder characterized by impaired biliary excretion of copper and excessive copper accumulation in multiple organs, primarily leading to hepatic, neurological, and psychiatric manifestations. The coexistence of WD and systemic lupus erythematosus (SLE) has rarely been reported, posing challenges in accurately diagnosing these two conditions because of overlapping clinical symptoms. Case presentation: We presented the case of a 17-year-old girl initially suspected of having SLE due to positive anti-nuclear antibodies and lupus anticoagulants, decreased platelet count, hypocomplementemia, and pleural effusion. However, the patient also exhibited an unusual manifestation of decompensated liver cirrhosis, which is not typical of SLE. Further investigation revealed low serum ceruloplasmin levels, high 24-h urine copper levels, the presence of Kayser-Fleischer rings, and a compound heterozygous mutation in the ATP7B gene, confirming the diagnosis of WD. Conclusion: The co-occurrence of WD and SLE poses a significant diagnostic challenge, often leading to misdiagnosis and delayed diagnosis. Therefore, in patients with well-controlled SLE presenting with unexplained liver fibrosis, neurological involvement, or psychiatric symptoms, it is crucial to consider the possibility of WD. However, further studies are required to elucidate the underlying pathophysiological mechanisms.

LncRNA Nron deficiency protects mice from diet-induced adiposity and hepatic steatosis.

Obesity, as a worldwide healthcare problem, has attracted more and more attention. Here we identify a long non-coding RNA NRON, which is highly conserved across species, as an important regulator of glucose/lipid metabolism and whole-body energy expenditure. Depletion of Nron leads to metabolic benefits in DIO (diet-induced obesity) mice, including reduced body weight and fat mass, improved insulin sensitivity and serum lipid parameters, attenuated hepatic steatosis and enhanced adipose function. Mechanistically, Nron deletion improves hepatic lipid homeostasis via PER2/Rev-Erbα/FGF21 axis coupled with AMPK activation, and enhances adipose function via activating the process of triacylglycerol hydrolysis and fatty acid re-esterification (TAG/FA cycling) and coupled metabolic network. These interactive and integrative effects cooperatively account for a healthier metabolic phenotype in NKO (Nron knockout) mice. Genetic or pharmacological inhibition of Nron may have potential for future therapy of obesity.

Management of Rheumatoid Arthritis With a Digital Health Application: A Multicenter, Pragmatic Randomized Clinical Trial.

IMPORTANCE: Digital health applications have been shown to be effective in the management of chronic diseases with simple treatment targets. The potential clinical value of digital health applications in rheumatoid arthritis (RA) has not been well studied. OBJECTIVE: To investigate whether assessing patient-reported outcomes using digital health applications could result in disease control for patients with RA. DESIGN, SETTING, AND PARTICIPANTS: This is a multicenter, open-label randomized clinical trial in 22 tertiary hospitals across China. Eligible participants were adult patients with RA. Participants were enrolled from November 1, 2018, to May 28, 2019, with a 12-month follow-up. The statisticians and rheumatologists who assessed disease activity were blinded. Investigators and participants were not blind to group assignment. Analysis was conducted from October 2020 to May 2022. INTERVENTIONS: Participants were randomly assigned at a 1:1 ratio (block size of 4) to a smart system of disease management group (SSDM) or a conventional care control group. Upon the completion of the 6-month parallel comparison, patients in the conventional care control group were instructed to use the SSDM application for an extension of 6 months. MAIN OUTCOMES AND MEASURES: The primary outcome was the rate of patients with disease activity score in 28 joints using the C-reactive protein (DAS28-CRP) of 3.2 or less at month 6. RESULTS: Of 3374 participants screened, 2204 were randomized, and 2197 patients with RA (mean [SD] age, 50.5 [12.4] years; 1812 [82.5%] female) were enrolled. The study included 1099 participants in the SSDM group and 1098 participants in the control group. At month 6, the rate of patients with DAS28-CRP of 3.2 or less was 71.0% (780 of 1099 patients) in the SSDM group vs 64.5% (708 of 1098 patients) in the control group (difference between groups, 6.6%; 95% CI, 2.7% to 10.4%; P = .001). At month 12, the rate of patients with DAS28-CRP of 3.2 or less in the control group increased to a level (77.7%) that was comparable with that (78,2%) in the SSDM group (difference between groups, -0.2%; 95% CI, -3.9% to 3.4%; P = .90). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of RA, the use of a digital health application with patient-reported outcomes was associated with an increase in disease control rate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03715595.

[A multicenter study of coronary artery disease and its risk factors in rheumatoid arthritis in China].

OBJECTIVE: To learn about the prevalence and risk factors of coronary artery disease (CAD) in rheumatoid arthritis (RA). METHODS: Data were obtained from a 12-month retrospective investigation of the patients with RA, randomly selected from Departments of Rheumatology and Immunology in 21 big hospitals in China. The data were collected about their social conditions, clinical conditions, medications associated with RA, such as disease modifying anti-rheumatic drugs (DMARDs), non steroidal anti-inflammatory drugs (NSAIDs), glucocorticoid, biologic agents. A nonparameter test and multivariate logistic regression analysis were performed. RESULTS: In the study, 960 patients were enrolled. The prevalence of CAD was 3.5% in China, which was obviously higher than that of normal people. The prevalence of overweight and obesity, smoking, hypertension, diabetes mellitus, hypercholesterolemia and cerebrovascular disease were 35.1%, 12.3%, 17.0%, 7.7%, 0.4% and 3.0%, respectively. Compared with the control group, the CAD group had higher age [(64.7±9.3) years vs. (52.3±14.0) years,P<0.001], more rheumatoid nodules (14.7% vs. 3.1%,P=0.005), lower rate of hydroxychloroquine (HCQ) use (5.9% vs. 22.6%,P=0.021), higher prevalence rates of lung interstitial disease (17.5% vs. 7.0%,P<0.001), diabetes mellitus and hypertension (29.4% vs. 7.0%,P<0.001; 38.2% vs. 16.2%,P=0.001). There was no obvious correlation of CAD in RA with joint deformity, rheumatoid factor (RF) titer, glucocorticoid use, hypercholesterolemia and body mass index (BMI). Multivariate analysis showed higher age, diabetes mellitus and hypertension were independent predictors of CAD, and the use of HCQ was a protective factor of CAD. CONCLUSION: The prevalence of CAD is 3.5%. Higher age, diabetes mellitus and hypertension are independent predictors of CAD, and the use of HCQ is a protective factor of CAD.

[Survey of tumor necrosis factor inhibitors application in patients with rheumatoid arthritis in China].

OBJECTIVE: To investigate the current status of tumor necrosis factor (TNF) inhibitors application in rheumatoid arthritis (RA) patients in China and to analyze the related factors. METHODS: A retrospective survey was conducted in 21 hospitals from different parts of China. The patients with RA were randomly enrolled. Data of their social backgrounds, clinical conditions, usage and adverse effects of TNF inhibitors were collected. The costs of TNF inhibitors and the indirect costs of the disease were calculated. A multivariate Logistic regression analysis was performed to analyze the factors related to TNF inhibitors application. RESULTS: In the study, 1 095 RA patients from July 2009 to November 2010 were enrolled, of whom 112 had received TNF inhibitors, representing 10.2% of the total patients. The patients who received etanercept and infliximab were 7.4% (86/1 095) of the patients and 2.4% (26/1 095), respectively. There were 0.5% of the patients (5/1 095) who had received both of the TNF inhibitors. The patients who had accepted etanercept and treatment duration for less than 3 months and 3-6 months accounted for 38.5% and 25.0% respectively, while those treated with Infliximab were 38.1%. Their health assessment questionnaire (HAQ) scores were 1.1, 0.5 and 0.1, corresponding to treatment duration of infliximab for less than 3, 3-6 and 6-9 months and those were 1.3, 1.0, 0.3 corresponding to treatment duration of etanercept, respectively. Infliximab costs were RMB 24 525.0, 69 300.0 and 96 800.0 Yuan and etanercept costs were RMB 7 394.8, 9 158.6, 54 910.9 Yuan, respectively. Indirect costs for RA patients who accepted infliximab for less than 3, 3-6 and 6-9 months were RMB 365.6, 0 and 158.9 Yuan and those who accepted etanercept were RMB 2 158.4, 288.5 and 180.1 Yuan, respectively. Allergy and infection were the main side-effects of etanercept and both happened in 3.5% of all the patients. Liver damage happened in 2.3% of all the patients, while allergy and infection happened in 6.5% of all the patients who accepted infliximab. Logistic regression analysis showed that patients with higher education experience increased the odds of entering the TNF inhibitors group (OR: 1.292, 95%CI: 1.132-1.473, P=0.000). CONCLUSION: About one-tenth of RA patients in China have accepted TNF inhibitors. Higher education experience is the key factor for using TNF inhibitors.

[Sulphasalazine in patients with rheumatoid arthritis in China: a cross-sectional study].

OBJECTIVE: To investigate the medication status of rheumatoid arthritis (RA) patients and to analyze the clinical use of sulphasalazine (SSZ) and the adverse effect. METHODS: A total of 1 096 outpatients and inpatients diagnosed with RA were investigated in 21 hospitals all over China from July 2009 to December 2010, including gender, age of onset, clinical manifestations, as well as the clinical characteristics and medication status of 160 RA patients who received SSZ therapy. RESULTS: In the group of 160 patients who received SSZ, the male-to-female ratio was 1:7, The average age at onset was (46.1±15.0) years, while the average course was (9.9±7.8) years. The average dose of sulphasalazine was (1.87±0.52) g/d for a mean duration of (26.3± 14.6) months. Only 17% (27/160) of the patients received SSZ monotherapy. Methotrexate (63.1%), leflunomide (36.2%) and hydroxychloroquine (18.1%) were most commonly used combination drugs. And 36.2% (58/160) of the patients used the two-drug combination of methotrexate plus sulphasalazine .In this group, 41.9% (67/160) once used SSZ but withdrew for adverse events and other reasons, while 17.5% (28/160) withdrew for adverse events, of which the most common were gastrointestinal (8.8%), skin (3.8%) and liver toxicity (3.1%). CONCLUSION: Sulphaszlazine is not a common choice in the RA therapeutics in China, and the average dose of SSZ is lower than the standard dose of 2 to 3 g/d . The adverse events of SSZ are common; however, there are few severe adverse events or threat to life,SSZ is relatively safe in clinical practice.