Background: The prognosis of anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+ DM) – associated interstitial lung disease (ILD) is poor and heterogeneity. Objectives: The aim of this study was to evaluate prognostic factors and to develop a simple and generally applicable bedside decision tree model for predicting outcomes in patients with anti-MDA5+ DM and to guide treatment. Methods: We analyzed data for 246 anti-MDA5+ DM patients from Myositis Study Group-Jiangsu, a multicenter cohort across eighteen tertiary hospitals in Jiangsu province, from March 2019 to October 2020. The primary end point was all-cause death, and the secondary end point was occurring of rapidly progressive-ILD (rp-ILD). We used a multivariable Cox proportional hazards model to identify the independent prognostic risk factors of death and rp-ILD respectively. A decision-tree prediction model was developed by using data from 10 hospital of southern region (n=163), with validation by using contemporaneous data from northern region (n=83). Results: To assess the risk of rp-ILD, we developed a combined risk score, the CROSS score, that included the following values and scores: C-reactive protein (≤8mg/L, 0; >8mg/L, 3), anti-Ro52 antibody (negative, 0; positive, 4), Sex (Female, 0; Male, 2) and Short course of disease (More than 3 months, 0; Less than 3 months, 2). The mortality risk was identified by the CAR score, including C-reactive protein (≤8mg/L, 0; >8mg/L, 1), Alanine Transaminase (≤50units/L, 0; >50units/L, 1) and rp-ILD (non-rpILD, 0; rp-ILD, 3). We divided patients into three risk groups according to the CROSS score: low, 0 to 3; medium, 4 to 7; and high 8-11. And then Use of a simple decision tree prediction model permitted stratification into three different outcome prediction groups. High-risk patients had significantly higher mortality rates than low- and medium-risk patients in both discovery and validation cohorts (p < 0.0001). Conclusion: The CROSS-CAR decision tree model is easy to evaluate the poor prognostic risk in MDA5+ DM patients during any follow-up period. Unnecessary lung examination, such as chest CT scan and arterial blood gas analysis was avoided in low- and medium- rpILD risk patients. The special ambulance, with red cross sign tagged on car in China, may help to screen the high risk patients and to guide further treatment. Disclosure of Interests: None declared

过敏性紫癜好发于儿童，发生于成年人的病例非常罕见，不容易确诊，特别是出现消化道出血和穿孔时，诊断更加困难。该文报道1例发生于西藏地区藏族成年男性的过敏性紫癜病例，患者病情危重、复杂，多系统器官受累，以消化道出血为主要表现，临床诊断困难。因发现小肠穿孔行急诊手术切除病变段小肠，经病理检查证实为血管炎并多学科会诊讨论，最终明确诊断为IgA血管炎（过敏性紫癜）。此类病例较少见，总结此类病变的临床病理特征，旨在加深对该疾病的认识，对临床及病理医师有所启发。

Background As the most common arthritis in adults, gout is a painful, inflammatory disease that may cause functional disability and decreased health-related quality of life (HRQoL). However, there are currently no known reported studies related to functional disability and HRQoL of gout patients from China. Objectives This cross-sectional study aims to investigate the effect of demographic variables, disease parameters, and psychological status on functional disability and HRQoL of Chinese gout patients. Methods A self-report survey was administered to 226 gout patients and 232 healthy individuals using the Short Form 36 health survey (SF-36) for HRQoL and the Health Assessment Questionnaire-Disability Index (HAQ-DI) for functional disability. Gout patients were asked to complete the 10 cm Visual Analog Scale (VAS) for total pain, the Patient Health Questionnaire (PHQ-9) for depression, and the Generalized Anxiety Disorder (GAD-7) questionnaire for anxiety. Blood samples were taken to examine the level of uric acid (UA). Independent samples t-tests, Chi square tests, spearman and/or pearson correlation and multiple linear regression were used to analyze the data. Results Our results found that individuals with gout have poorer HRQoL compared to healthy controls and the mean disability score was 0.32 (SD 0.54), representing mild disability. SF-36 and almost all components of the SF-36 score were associated with place of residence, hypertension, DM, cardiovascular disease, disease duration, number of flares/last year, total pain, number of tophi, presence of tender joints, colchicines use, corticosteroids use, depression, and anxiety (p<0.05). This variable was also significantly related to the HAQ-DI score (p<0.05). Additionally, there were significant relationships among age, income/year, allopurinol use and HAQ-DI (p<0.05). Stepwise multiple linear regression identified number of flares/last year, place of residence, depression and DM as predictors of functional disability. Disease status (total pain, number of flares/last year, presence of tender joints, cardiovascular disease, colchicine and corticosteroids use) and psychological disorders (depression and anxiety) were significantly accounted for poor HRQoL. Conclusions Chinese gout patients experienced mild disability and poor HRQoL. Disease status and psychological status were important risk factors linked to functional disability and HRQoL in Chinese gout population. These data suggest medical personnel should pay more attention to functional disability and HRQoL of gout patients and make suitable interventions to relieve their psychological disorders and finally to reduce their functional ability and improve their HRQoL. Acknowledgements This study was supported by Grants from the Chinese National Natural Science Foundation (no. 81671616 and 81471603). Disclosure of Interest None declared

Background Poor sleep quality is common in patients with chronic diseases and may lead to disease aggravation and decreased quality of life. The increasing prevalence of poor sleep in individuals with chronic medical conditions is associated with adverse demographic, clinical, and psychological characteristics. However, there are currently no known reported studies related to the sleep quality of gout patients. Objectives This study aims to evaluate the prevalence of poor sleep quality and investigate the contributors of poor sleep in Chinese gout patients. Methods A self-report survey was administered to 226 gout patients and 232 healthy individuals using the Pittsburgh Sleep Quality Index (PSQI) for sleep quality, the Patient Health Questionnaire (PHQ-9) for depression, and the Generalized Anxiety Disorder (GAD-7) questionnaire for anxiety. Gout patients completed the 10 cm Visual Analog Scale (VAS) for total pain, and the Health Assessment Questionnaire-Disability Index (HAQ-DI) for functional capacity. Blood samples were taken to examine the level of uric acid (UA). Independent samples t-tests, Chi square analyses, and logistic regression were used to analyze the data. Results Our results found that the prevalence of poor sleep (PSQI≥5) was 55.3% and the mean global score of PSQI was 6.69 (SD 3.48) in patients, which were significantly higher than the controls (17.7% and 3.83 (SD 1.88), respectively). There were significant correlations among alcohol use, HAQ-DI, PHQ-9, GAD-7 and sleep quality in gout patients. Patients with yellow rice wine and wine use preferred to have better sleep quality. While, disease stage was associated with hypertension, total pain, number of tophi, presence of tender joints and swollen joints. Meanwhile, logistic regression models identified alcohol use and depression as predictors of poor sleep quality. Conclusions More than half of Chinese gout population suffered from poor sleep, which significantly higher than healthy individuals. These findings suggested medical personnel should pay more attention to the sleep quality of gout patients, especially those with depression. Additionally, it is beneficial for the patients with normal UA level to take moderate yellow rice wine and wine to improve their sleep quality. Acknowledgements This study was supported by Grants from the Chinese National Natural Science Foundation (no. 81671616 and 81471603). Disclosure of Interest None declared

The objective of this study is to evaluate the association of clinical features and prognosis with age at disease onset in patients with systemic lupus erythematosus (SLE) in a large, multicenter Chinese cohort. Medical records of 1898 SLE inpatients from 15 hospitals were reviewed and classified into three groups according to their ages at disease presentation. Categorical data were analyzed by chi-square test and potentially associated factors were tested by multinomial logistic regression. Among the patients studied, 259 (13.6%) were juvenile onset (≤18 years), 1444 (76.1%) were early onset (>18 and ≤45 years) and 195 (10.3%) were late onset (>45 years). Whenever manifestations occurred, most patients (>80%) were diagnosed within two years. Juvenile-onset patients were more likely to be untreated before admission ( p < 0.001) and have mucocutaneous manifestations ( p < 0.001), but musculoskeletal symptoms ( p < 0.05) and leukopenia ( p < 0.05) were less frequent, while comorbidities were much higher in patients with late-onset SLE ( p < 0.001). Neuropsychiatric, cardiopulmonary, renal and gastrointestinal involvement, disease activity index and damage scores were similar among three groups. Anti-Sm antibodies were less prevalent in late-onset patients ( p < 0.05) and antimalarial drugs were more often applied to juvenile-onset patients ( p < 0.001). As expected, mortality was elevated in the late-onset SLE group ( p < 0.05), in which nearly half died of infections, which was much higher than those in the other two groups ( p < 0.001). Logistic regression confirmed that patients with juvenile- and early-onset disease were associated with high incidence of being untreated prior to admission, and with low incidence of comorbidities as well as deaths caused by infection compared to patients with late-onset lupus. Interestingly, our data showed that more patients with late-onset disease had a SLEDAI score change of >7 at discharge. In conclusion, age at onset has an impact on SLE disease status, and infection is the main cause of death in those with late-onset lupus. Considering that the late-onset patients had simultaneously easily controllable diseases and high incidence of comorbidities, a different treatment strategy from younger patients should be considered.

OBJECTIVES To identify the socioeconomic status, disease activity and psychiatric disorders that contribute to the health-related quality of life (HRQOL) in systemic lupus erythematosus (SLE) patients. METHODS Data were collected from 170 SLE patients and 210 healthy individuals. All of the patients fulfilled the criteria for the classification of SLE and underwent disease activity assessment according to the SLE disease activity index (SLEDAI). Self-rated scales for anxiety (SAS) and depression (SDS) were used to evaluate the levels of anxiety and depression. The patients' general health status was measured using the Short Form (SF)-36 questionnaire. To provide greater clarity regarding the determinants of HRQOL, path analysis was used to explore the relationships between the various predictors and the health-related quality of life (HRQoL). RESULTS SLE patients who have depression and anxiety are more likely to have a lower quality of life compared to those who are not depressed (r=-0.735, p<0.01; r=-0.684, p<0.01). All of the variables were significantly correlated with depression except age, gender and marital status. Education was negatively correlated with disease activity (r=-0.272, p<0.05) and anxiety (r=-0.312, p<0.01). Disease activity was positively correlated with anxiety (r=0.198, p<0.05). In addition, work status also correlated with anxiety (r=-0.294, p<0.01). A path-analytic models analysis suggested that the main influencing factors of HRQoL are the following: depression, anxiety, education level, income/family, disease activity, age, and work status. A χ2 test (χ215=17.71, p=0.28>0.05) indicated that the path analysis model had an adequate goodness of fit value. Depression (β=-0.616, p<0.05) contributed the most to HRQOL. Depression, anxiety and disease activity contributed to HRQoL both directly and indirectly through other factors. Socioeconomic factors such as education, income/family and work status, however, did not contribute directly to HRQoL. CONCLUSIONS HRQoL in SLE is influenced by disease activity and psychiatric disorders. Socioeconomic status has no direct influence on the quality of life of lupus patients, while disease activity has a direct impact on the quality of life. Anxiety and depression were significant predictors of poor HRQoL. Understanding how these factors are inter-related may help clinicians focus their assessments and develop strategies to improve the HRQoL of lupus patients.

Abstract Recent studies have shown that autologous and allogeneic transplantation of the BM-MSCs had therapeutic effects on T1DM, whereas the BM-MSCs from the NOD mice itself did not have this therapeutic effect. We previously demonstrated that Bone Marrow (BM) -MSCs from the non-obese diabetic (NOD) mice had the abnormal migration and adhesion. So we hypothesized that the proliferation and apoptosis of the BM-MSCs from the NOD mice were dysregulated. Our team compared the proliferation and apoptosis between NOD mice and imprinting control region (ICR) mice. Then we assessed whether the NF-κB-p53/p21 pathway was involved in the process. The cell proliferation ability of the BM-MSCs from the NOD mice were significantly decreased, while the percent of apoptotic cells was increased compared to those from the ICR mice. The p21 expression was significantly increased in the NOD-MSCs. The p65 level was enhanced in the BM-MSCs from the NOD mice when compared to the ICR mice, coincided with the expression of p21. Expressions of p65 and p21 were significantly decreased in the BM-MSCs treated with p65 inhibitor. The knockdown p21 expression reversed the abnormal proliferation, colony formation and apoptosis of the BM-MSCs from the NOD mice. These data provide important preclinical references supporting the basis for further development of autologous MSC-based therapies for type1 diabetes mellitus (T1DM).

Prolonged warm ischemia (WI) occurring in marginal kidney donors together with reperfusion injury determines allograft survival, in which apoptosis and inflammation play crucial roles. There is no single valid biomarker, so far, to assess the degree of kidney donor injury. To define new biomarkers for detecting initial donor ischemic injury, caspase-3, caspase-7, apoptosis, inflammation, HSP70 and renal histological changes were examined in porcine kidneys subjected to 7- 15- 25- or 40-min WI, two-hour cold storage and six-hour hemoreperfusion. Caspase-3 activity was gradually increased by prolonged reperfusion, with a decrease trend against WI time. This result was verified by raised 17 kDa active caspase-3 in postreperfusion kidneys, with elevated 12 kDa active caspase-3 and lowered precursor at seven-minute WI. Active caspase-7 was also doubled by reperfusion with decreased precursor at seven-minute WI, but declined against prolonged WI. Apoptotic cells in tubular and interstitial areas were greatly increased by reperfusion at seven-minute WI, but decreased against prolonged WI. In addition, myeloperoxidase (MPO)+ cells were dramatically increased by reperfusion and presented as a bell-shape against WI time, while HSP70 was significantly increased at 7-min WI, but decreased at 40-min WI after reperfusion. In postreperfusion kidneys, tubular dilation and cell shedding were observed at 7- and 15-min WI, while tubular vacuolation and cell debris were found in tubular lumens at longer WI times. At 40-min WI, early nuclear pyknosis, tubular epithelia detachment and peri-tubular capillary dilation were detected. Furthermore, caspase-3, caspase-7, apoptosis, but not MPO+ cells or HSP70, were correlated with renal function. In conclusion, caspase-3, caspase-7 and apoptosis appear to be better biomarkers than MPO+ cells or HSP70 for assessing warm ischemic injury in donor kidneys. Hemoreperfusion activates caspase-3 and caspase-7, promotes apoptosis of damaged cells in kidneys only with limited WI, which might be beneficial to renal structural re-modeling and functional recovery.

Introduction: Renal transplantation is the most cost-effective treatment for end-stage renal failure. Allograft survival is improved in 1 year, but falls dramatically in 10 years. To allow timely interventions, there is imperative need to understand choreographed processes in adaptive-immune responses including inflammation, apoptosis and fibrosis, and to define efficient assessments for ischaemia/reperfusion injury, rejection and calcineurin inhibitor nephrotoxicity. However, no single conventional method could fit in with the purpose. Modern screening techniques such as genome have provided opportunities to develop potential novel biomarkers. Herein, transcriptomic signatures were investigated in human transplanted renal tissues. Methods: In Leicester, 80 patients per year in average are transplanted with kidneys, comprising 61% living unrelated/living related donors (LURD/LRD) and 39% cadaveric donors (CAD). Total RNAs were extracted from 24 renal biopsies at 30 minutes and 3 months post-transplantation from both donor groups (n = 6). The quality and quantity of total RNAs were assessed on a bioanalyzer. Whole-geneome expression profiling was examined using Illumina HumanHT-12 Expression BeadChips with 48,000 probes targeting 25,000 annotated genes. Raw data analysis was processed using Illumina Genome studio software. Student's t-test, unsupervised hierarchical clustering and principal component analysis (PCA) were performed using ArrayTrack, an integrated bioinformatics tool for managing, analyzing and interpreting microarray gene expression dada developed by the U.S. Food and Drug Administration National Center for Toxicological Research (NCTR/FDA). Ingenuity software was used for function annotation analysis. The gene profiling was assessed in four comparisons: CAD vs. LURD/LRD at 30 minutes or 3 months; LURD/LRD or CAD at 3 months vs. 30 minutes. Results: Unsupervised hierarchical clustering and PCA analysis revealed that the overall profiles in 3-month samples were clearly different from that in 30-minute samples regardless of donor types. At 30 minutes, 681 genes were differentially expressed in the CAD group compared to that in the LURD/LRD group (p < 0.05, fold change at 1.5), whereas at 3 months differentially expressed genes were reduced to 75. Function annotation analysis showed that many acute phase response genes (C9, FGA, VWF, SERPINA 1 & 3) were up-regulated at 30 minutes, while genes mostly involved in inflammation, tubular toxicity and cell proliferation were up-regulated at 3 months, with highly expressed renal cellular apoptosis associated genes (AGT, CASP1, CDKN1A, DCN, EGF, IGF1, MAFB and LCN2) in the CAD group, but only tubulointerstitial damage related genes (HBEGF, MDK and LCN2) in the LURD/LRD group. More interestingly, in the CAD group the altered gene expression with up-regulated apoptosis and tissue remodeling associated genes (COL3A1, TIMP1 & 4, and MMM9) and down-regulated FGA at 3 months in contrast to 30 minutes was not seen in the LURD/LRD group. Conclusion: There were more differentially expressed genes in transplanted renal tissues between different donors at the early stage than that in the later stage. Transcriptomic signatures were changed by the time post-transplantation and shifted from acute responses to tissue damage and remodeling with divergent profiles in two donor types. These results need to be further validated in long-term follow-up studies with more samples and detailed clinical outcomes.

Subunit vaccines have the potential advantage to boost Mycobacterium bovis Bacillus Calmette-Guerin (BCG)-primed immunity in adults. However, most candidates are antigens highly expressed in replicating bacilli but not in dormant or persisting bacilli, which exist during Mycobacterium tuberculosis infection. We constructed M. tuberculosis fusion protein Ag85B-Mpt64(190-198)-HspX (AMH) and Ag85B-Mpt64(190-198)-Mtb8.4 (AMM), which consist of Ag85B, the 190-198 peptide of Mpt64, HspX (Rv2031c) and Mtb8.4 (Rv1174c), respectively. AMH and/or AMM were mixed with adjuvants composed of dimethyl-dioctyldecyl ammonium bromide and BCG polysaccharide nucleic acid (DDA-BCG PSN) to construct subunit vaccines. Mice were immunized thrice with Ag85B, AMH and AMM vaccines and the immunogenicity of the fusion protein vaccines was determined. Then, mice were primed with BCG and boosted twice with Ag85B, AMH, AMM and AMM + AMH vaccines, respectively, followed by challenging with M. tuberculosis virulent strain H37Rv, and the immune responses and protective effects were measured. It was found that mice immunized with AMH vaccine generated high levels of antigen-specific cell-mediated responses. Compared with the group injected only with BCG, the mice boosted with AMM, AMH and AMM + AMH produced higher levels of Ag85B-specific IgG1 and IgG2a and IFN-gamma-secreting T cells upon Ag85B and Mycobacterium tuberculosis purified protein derivative (PPD) stimulation. It is interesting that only mice boosted with AMM + AMH had significantly lower bacterial count in the lungs than those receiving BCG, whereas mice boosted with AMH or AMM did not. The results suggest that AMH consisting of HspX, the antigen highly expressed in dormant bacilli, could be combined with antigens from replicating bacilli to enhance BCG primed immunity so as to provide better protection against both growing and non-growing bacteria that occur during the infection process.

Mycobacterium bovis bacillus Calmette-Guérin (BCG) priming and subunit vaccine boosting strategies are urgently needed to improve the protective efficacy of BCG in adult population. However, the schedule of subunit vaccine boosting is not well investigated, especially the optimal immune responses and vaccine immunization schedules are still not clear. We have constructed a novel subunit vaccine candidate consisting of fusion protein Ag85B-Mpt64 (190-198)-Mtb8.4 (AMM) in a complex adjuvant composed of dimo-thylidioctyl ammonium bromide (DDA) and BCG polysaccharide nucleic acid (BCG-PSN). In this study, we compared the effect of different boosting schedules of the subunit vaccine in the prime-boost strategies. C57BL/6 mice were primed with BCG first and then boosted with the AMM vaccine once at 10th week, twice at 8th, 10th week, or thrice at 6th, 8th, 10th week, respectively. The immune responses were evaluated at the 14th and 20th weeks, respectively. Twelve weeks after the last immunization, the mice were challenged with virulent Mycobacterium tuberculosis strain H37Rv, and the protective effect was evaluated. The results showed that BCG priming and the AMM vaccine boosting twice induced the strongest antigen-specific IFN-γ and IL-2 production, down-regulated CD4+ CD25+ FoxP3+ regulatory T cells (Tregs) and had the best protective effect among all groups, while boosting thrice induced the strongest IL-4 production and did not improve BCG-primed protection significantly. Boosting BCG with the AMM vaccine twice instead of once or thrice induced strong Th1-type immunity and down-regulated Tregs significantly, which correlated with the best protection against M. tuberculosis infection in mice.

Structure stabilized Y (SSY) zeolite with high rare earth content was prepared by following the RE3+-exchange of NaY with a SiCl4 treatment. Due to RE3+ cation location in the zeolite lattice, migrating direction and presence state could be well controlled in processing, the SSY possesses the following characteristics: initial unit cell constant a(0) = 2.450-2.458nm, equilibrium unit cell size > 2.435nm, RE2O3 content could be adjusted within 6-14wt%, sodium oxide content less than 1.0wt%, and a differential thermal collapsed temperature, DTA > 1000 degrees C. Research results indicate that the SSY with an improved heavy oil conversion, a better coke selectivity and a higher hydrogen transfer activity and stability is suitable as an active component of cracking catalyst for clean gasoline production.

The alkylation of toluene with 1-heptene and 1-dodecene were used as model reactions for the synthesis of long-chain linear alkylbenzenes, the precursors of biodegradable surfactants. The effect of the pore structure of large pore zeolites: HFAU (framework Si/Al=15) and HBEA (framework Si/Al=12.5) on their catalytic properties was determined in liquid phase at 90°C with a toluene/alkene molar ratio of 3. With these large pore zeolites, the main reactions are alkene double bond shift and toluene alkylation. Monoalkyltoluenes are the main reaction products, whereas bimonoalkyltoluenes and alkene dimers appear in low amount from, respectively, HFAU and HBEA. HBEA, despite the small size of its crystallite is practically inactive for the toluene alkylation by 1-dodecene. This low activity can be attributed to the slow desorption of the reaction product from the narrow pore of this zeolite and more particularly the non-desorption of the 3- to 6-monododecyltoluenes. These steric constraints lead to the formation of bulky aromatic compounds in the HBEA micropores. These components formed in larger amount than over HFAU, are responsible to the blockage of the alkenes (dodecene mixture and dimers) in the zeolite pores. However, the limitation effect of diffusion steps observed in the pore of HBEA leads to increase the selectivity to 2-phenylalkanes which are the most biodegradable isomers.

The alkylation of toluene with 1‐dodecene was carried out over a HFAU zeolite (total and framework Si/Al ratio = 25) under the following conditions: fixed‐bed reactor, 90°C, molar toluene/dodecene ratio of 3, WHSV =10 h−. Monododecyltoluenes are selectively formed, bidodecyltoluenes appearing only in low amounts at a complete conversion of dodecene. Tridodecyltoluenes are also formed inside the supercages but cannot desorb from the zeolite. These compounds, mainly located in the outer part of the crystallites are responsible for catalyst deactivation. However, tridodecyltoluenes can be completely removed by treatment under toluene flow, which allows a complete regeneration of the catalyst. This removal occurs by transalkylation between tridodecyltoluenes and toluene molecules with a final formation of monododecyltoluenes. At least, the first transalkylation steps occur between toluene in the liquid phase and tridodecyltoluenes in the zeolite pores (pore mouth catalysis).

The liquid phase alkylation of toluene with 1-heptene was investigated over a HFAU zeolite (Si/Al=6) under the following conditions: batch reactor, 90°C, molar toluene/heptene ratio=3. Monoheptyltoluenes are rapidly formed, whereas biheptyltoluenes appear in low amount at high conversion. A large amount of mono, bi and triheptyltoluenes is shown to be trapped in the zeolite pores, suggesting that alkylation is limited by product desorption. After total consumption of heptene, there is an increase with reaction time in monoheptyltoluenes trapped in the pores and a decrease in bi and triheptyltoluenes. These observations can be explained both by a transalkylation reaction between bi and triheptyltoluenes trapped in the zeolite micropores and toluene molecules and by a slow diffusion of monoheptyltoluenes from the liquid phase to the zeolite micropores.