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Background. Intensive therapy with disease modifying anti-rheumatic drugs (DMARDs) has been reported to improve the outcomes of rheumatoid arthritis (RA). However, real-world study on the effect of intensive therapy on RA sustained remission is still lacking. This study aimed to investigate the outcome of sustained intensive DMARD therapy (SUIT) for RA in a real-world 5-year consecutive cohort. Methods. Based on a consecutive cohort of 610 out-patients with RA, remission of RA was assessed in 541 patients from 2012 to 2017, by dividing into SUIT, non-SUIT, and intermittent SUIT (Int-SUIT) groups. Changes in the disease activity scores were evaluated by 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), 28-joint disease activity score based on C-reactive protein (DAS28-CRP), and clinical deep remission criteria (CliDR). Cumulative remission rates between different groups were compared using Kaplan-Meier curves and predictive factors of sustained remission were identified by univariate and multivariate logistic regression analysis. Results. The remission rates of the SUIT group decreased from 12.0% (65/541) to 5.6% (20/359) based on DAS28-ESR, from 14.0% (76/541) to 7.2% (26/359) based on DAS28-CRP, and from 8.5% (46/541) to 3.1% (11/359) based on CliDR, respectively, with a gradually decreasing trend during the 5 years. The SUIT regimen led to a significantly higher cumulative remission rate than non-SUIT regimen based on DAS28-ESR (39.7% vs. 19.5%, P = 0.001), DAS28-CRP (42.0% vs. 19.6%, P = 0.001), and CliDR (24.5% vs. 8.7%, P = 0.001). The cumulative remission rates of patients treated with SUIT regimen were significantly higher than those treated with Int-SUIT regimen based on DAS28-ESR (39.7% vs. 25.7%, P = 0.043) and CliDR (24.5% vs. 14.2%, P = 0.047), but there was no significant difference between the two groups based on DAS28-CRP (42.0% vs. 27.4%, P = 0.066). Multivariate logistic regression analysis showed that the use of SUIT regimen was an independent favorable predictor according to different remission definitions (for DAS28-ESR: odds ratio [OR], 2.215, 95% confidence interval [CI]: 1.271–3.861, P = 0.005; for DAS28-CRP: OR, 1.520, 95% CI: 1.345–1.783, P = 0.002; for CliDR: OR, 1.525, 95% CI: 1.314–1.875, P = 0.013). Conclusion. Sustained intensive treatment of RA is an optimal strategy in daily practice and will lead to an increased remission rate.

Background: Clinically amyopathic dermatomyositis (CADM) is a unique sub-type of idiopathic inflammatory myopathies with a high prevalence of interstitial lung disease (ILD). Poor prognosis of the patients was strongly associated with rapid progressive ILD. The aim of this study was to identify risk factors for prediction of different types of ILD in CADM. Methods: In this study, data of 108 inpatients with CADM were collected, including 87 with ILD. The baseline clinical data and laboratory parameters, including myositis-specific and associated antibodies and tumor-associated antigens were analyzed to identify risk factors for acute or subacute interstitial pneumonitis (A/SIP) and chronic interstitial pneumonitis (CIP). Results: In 87 patients with CADM-ILD, 39 (36.1%) were A/SIP, and 48 (44.4%) were CIP. There were 22 (20.4%) patients with asymptomatic ILD who were detected by routine high resolution computed tomography. Cytokeratin-19 fragment (CYFRA21-1) was significantly higher in CADM-ILD than that in CADM patients without ILD; carcinoembryonic antigen and neuron-specific enolase were significantly elevated in A/SIP than that in CIP. Patients with A/SIP had a higher positive rate of anti-melanoma differentiation-associated gene 5 (MDA5), while patients with CIP had a higher positive rate of anti PL-12 and anti-Ro-52. Logistic regression analysis indicated that elevation of CYFRA21-1 was a risk factor for ILD, higher titer of anti-MDA5 indicated increased likelihood for A/SIP, and higher titer of anti-Ro-52 was also clearly associated with CIP. Conclusions: This study indicated that the prevalence of ILD was high in CADM. Asymptomatic ILD has been previously underestimated. Anti-MDA5 was a risk factor for the presence of A/SIP, and CYFRA21-1 was a risk factor for ILD. Key words: Clinically amyopathic dermatomyositis; Interstitial lung diseases; Myositis autoantibodies; Tumor-associated antigen

Background:. Psoriatic arthritis (PsA) is an inflammatory arthropathy characterized by psoriasis and bone erosion on radiology. Dickkopf-1 (Dkk-1) is considered to be the main inhibitor of the Wnt signaling pathway and results in reduced osteoblast proliferation. The aim of this study was to investigate the serum level of Dkk-1 and its association with bone erosion in PsA patients. Methods:. Serum Dkk-1 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 69 patients with PsA and 60 controls, including 39 rheumatoid arthritis (RA) patients, and 21 healthy controls (HCs). Rheumatoid factor and anti-cyclic citrullinated peptide levels were also determined by ELISA. The association of Dkk-1 level with clinical and laboratory features of PsA was analyzed. Logistic regression analysis was used to analyze the risk factors for bone erosion in PsA. Results:. Dkk-1 was elevated in 68.1% (47/69) of the patients with PsA, 46.2% (18/39) of RA patients, and 9.5% (2/21) of HCs. Serum Dkk-1 concentration was significantly higher in PsA patients compared with that in HCs. The level of serum Dkk-1 was correlated with a swollen joint count, and levels of complement components 3 and 4. Elevated Dkk-1 level (odds ratio = 4.440, 95% confidence interval: 1.246–15.817, P = 0.021) was identified as the risk factor for bone erosion in PsA. Conclusions:. The serum level of Dkk-1 is abnormally elevated in PsA patients. The elevation of Dkk-1 might be involved in the mechanism of bone erosion in patients with PsA.

Background: Clinical remission is the treatment target in rheumatoid arthritis (RA). This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA. Methods: This study composed of 342 patients with RA. Data were collected by face-to-face interview of 1049 patients with RA who visited the Department of Rheumatology of three teaching hospitals from September 2015 to May 2016. The patients with RA were clinically assessed by rheumatologists and a four-page questionnaire was completed on site. Subsequently, patients fulfilled remission criteria were further analyzed. The practicability of different definitions of remission of RA was rated by a panel of rheumatologists. Sustained intensive disease modifying anti-rheumatic drug (DMARD) treatment was defined as a combination treatment with two or more DMARDs for at least 6 months. Results: In this cohort of 342 patients with RA, the proportions of patients achieving remission were 38.0%, 29.5%, 24.9%, 21.1%, 19.0%, 18.1%, and 17.0%, based on criteria of disease activity score in 28 joints (DAS28) using CRP (DAS28-CRP), DAS28 using ESR (DAS28-ESR), routine assessment of patient index data 3 (RAPID-3), Boolean, simplified disease activity index (SDAI), clinical disease activity index, and the newly described clinical deep remission (CliDR), respectively. Boolean and CliDR are the best in practicability scored by rheumatologists (7.5 and 8.0, respectively). Compared with the non-sustained intensive group, sustained intensive treatment with DMARDs yielded higher remission rates of 25.6%, 23.8%, and 21.3% in patients with RA based on Boolean (χ2=3.937, P=0.047), SDAI (χ2=4.666, P=0.031), and CliDR criteria (χ2=4.297, P=0.038). The most commonly prescribed conventional synthesized DMARDs (csDMARDs) in patients with RA was leflunomide, followed by methotrexate, and hydroxychloroquine. Compared with the non-remission group, patients achieving remission had a longer median duration of DMARDs (45.0 [22.8–72.3] months, Z=-2.295, P=0.022). Conclusions: The findings in this study indicated that clinical deep remission is achievable in patients with RA. Sustained intensive DMARD treatment is needed to achieve a better outcome in RA. Key words: Rheumatoid arthritis; Remission; Sustained; Intensive; Disease modifying anti-rheumatic drug

\The development of effective delivery system for peptides targeting to the tumor microenvironment has always been a hot topic in the field of cancer diagnosis and therapy. A multifunctional delivery system by encapsulating superparamagnetic iron oxide nanoparticles (SPIO NPs) with tumor cell membrane obtained by hypotonic lysis followed by mechanical fragmentation was constructed to effectively deliver therapeutic peptides. SPIO nanoparticles were encapsulated with H460 lung cancer cell membranes (SPIO NP@M) and peptides consisted of PD-L1 inhibitory peptide (TPP-1) and MMP2 substrate peptide (PLGLLG) was conjugated to H460 membrane (SPIO NP@M-P). The abilities of homologous targeting, cytotoxicity, pharmacokinetics, and tumor targeting ability of SPIO NP@M-P were evaluated. TPP-1 peptide was delivered and released to the tumor microenvironment through the homotypic effect of tumor cell membrane and specific digestion by the tumor specific enzyme, MMP2. The newly developed delivery system (SPIO NP@M-P) for PD-L1 inhibitory peptide could effectively extend the half-life of the peptides (60 times longer) and meanwhile maintain the ability to re-activate T cell and inhibit the tumor growth in vitro and in vivo. Furthermore, SPIO NPs in the system could be used as a tumor imaging agent and thus indicate the effect of peptide treatment. The SPIO NP@M might provide a promising theranostic platform for therapeutic peptide application in cancer therapy.

Previous studies in other provinces of China (Beijing, Xinjiang, Shanxi, Jiangxi, Shanghai, Guangdong, and Taiwan) suggest that the distributions of lymphoma subtypes differ compared with Western populations. In order to evaluate the characteristics of malignant lymphoma in Sichuan, China, we analyzed case series data from incident lymphoma patients diagnosed in 2008 from three hospitals, including a total of 1629 cases and including only current residents of Sichuan. The median age of diagnosis for cases was 54 years, with a higher proportion of male cases compared with female cases. The most commonly diagnosed subtypes included diffuse large B-cell lymphoma (40.4%), NK/T-cell lymphoma (NKTCL; 11.8%), mixed cellularity Hodgkin lymphoma (7.0%), mantle cell lymphoma (4.8%), and marginal zone B-cell lymphoma (3.9%). Differences in demographic characteristics between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) cases were apparent for median age at diagnosis (HL: 34 years; NHL: 57 years), and NHLs accounted for nearly all (99.3%) of the 931 cases of extranodal lymphoma. These findings indicate a higher proportion of NKTCL cases and a lower proportion of follicular lymphoma cases (2.3%) in these hospitals in Sichuan, relative to reports from some other provinces within China (e.g., Shanghai and Shanxi) and the USA. Copyright © 2015 John Wiley & Sons, Ltd.

1. Elevated serum bilirubin levels are caused mainly by liver diseases, haematolysis, genetic defects and drug intake. Unconjugated bilirubin (UCB) is taken up into hepatocytes by human organic anion transporting polypeptide 1B1 (OATP1B1; encoded for by the SLCO1B1 gene). The present study was performed to determine the association between SLCO1B1 gene polymorphisms and serum bilirubin levels in vivo. Moreover, the effects of administration of low-dose rifampicin on serum bilirubin levels in different SLCO1B1 genotypes was examined. 2. Serum bilirubin levels were examined in 42 healthy volunteers who had been analysed for SLCO1B1 genotype (seven, 13, 14 and eight with SLCO1B1 genotypes *1a/*1a, *1b/*1b, *1b/*15 and *15/*15, respectively). Among them, 24 subjects (seven, seven, eight and two with SLCO1B1 genotypes *1a/*1a, *1b/*1b, *1b/*15 and *15/*15, respectively) were selected to participate in an open-label, two-phase clinical trial. Each was given 450 mg rifampicin orally once daily at 2000 hours for 5 consecutive days. Serum bilirubin concentrations at 0800 hours on the 1st and 6th days were compared between the different SLCO1B1 genotypes. 3. In the 42 volunteers, the mean (+/-SD) serum UCB in both SLCO1B1*1b/*15 and *15/*15 groups was significantly higher than that in the SLCO1B1*1b/*1b group (11.07 +/- 2.31, 13.01 +/- 3.87 and 8.21 +/- 2.68 micromol/L, respectively; P = 0.009 and P < 0.001). Total bilirum (T.BIL) in both the SLCO1B1*1b/*15 and *15/*15 groups was significantly higher than that in the SLCO1B1*1b/*1b group (16.69 +/- 4.09, 20.71 +/- 5.12 and 13.06 +/- 5.12 micromol/L, respectively; P = 0.029 and P < 0.001). The direct bilirubin (D.BIL) in the SLCO1B1*15/*15 group was significantly higher than that in the SLCO1B1*1b/*1b group (7.69 +/- 1.81 vs 4.85 +/- 1.81 micromol/L, respectively; P = 0.001). Rifampicin significantly increased UCB, T.BIL and D.BIL concentrations in 24 healthy volunteers (17.68 +/- 5.96 vs 13.95 +/- 4.44 micromol/L (P = 0.040), 5.72 +/- 2.01 vs 4.35 +/- 1.50 micromol/L (P = 0.028) and 12.00 +/- 4.26 vs 9.61 +/- 3.15 micromol/L (P = 0.035), respectively). However, the extent of the increase in serum bilirubin caused by 450 mg rifampicin for 5 days was not affected by SLCO1B1 genotype. 4. Genetic polymorphism in SLCO1B1 is a major determinant of interindividual variability in the serum bilirubin level. SLCO1B1*15 carriers had higher baseline serum UCB, T.BIL and D.BIL levels compared with subjects with the SLCO1B1*1a/*1a and SLCO1B1*1b/*1b genotypes. SLCO1B1*15/*15 homozygotes are more susceptible to hyperbilirubinaemia. Serum bilirubin levels could be increased by low-dose rifampicin administration, but the extent of the increase was not associated with SLCO1B1 genotype.

A stimuli-responsive porous hydrogel was synthesized from wheat straw hemicellulose using CaCO3 as the porogen, and its application for the removal of methylene blue was studied. The porous structure of the prepared hydrogel was confirmed by SEM analysis. The effects of pH and polyelectrolyte on the swelling of the hydrogels were discussed, and the porous hydrogels showed excellent sensitivity to pH and salt. The deswelling kinetic study indicated that the hydrogels exhibited rapid shrinking in NaCl aqueous solutions. The methylene blue adsorption on the hydrogels was investigated, and the obtained adsorption data was fitted to the pseudo-first-order, pseudo-second-order and intra-particle diffusion kinetics models, and the pseudo-first-order kinetic model could describe the adsorption process, and the adsorption process of methylene blue on the hydrogels was controlled by external film diffusion. This study reported that the hemicellulose-based porous hydrogel is promising for water treatment. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41606.