Investigation of Pb-B Bonding in PbB2(BO)n- (n = 0-2): Transformation from Aromatic PbB2- to Pb[B2(BO)2]-/0 Complexes with BB Triple Bonds.

Boron has been found to be able to form multiple bonds with lead. To probe Pb-B bonding, here we report an investigation of three Pb-doped boron clusters, PbB2-, PbB3O-, and PbB4O2-, which are produced by a laser ablation cluster source and characterized by photoelectron spectroscopy and ab initio calculations. The most stable structures of PbB2-, PbB3O-, and PbB4O2- are found to follow the formula, [PbB2(BO)n]- (n = 0-2), with zero, one, and two boronyl ligands coordinated to a triangular and aromatic PbB2 core, respectively. The PbB2- cluster contains a BB double bond and two Pb-B single bonds. The coordination of BO is observed to weaken Pb-B bonding but strengthen the BB bond in [PbB2(BO)n]- (n = 1, 2). The anionic [PbB2(BO)2]- and its corresponding neutral closed-shell [PbB2(BO)2] contain a BB triple bond. A low-lying Y-shaped isomer is also observed for PbB4O2-, consisting of a central sp2 hybridized B atom bonded to two boronyl ligands and a PbB unit.

Interventions to reduce burnout and improve the mental health of nurses during the COVID-19 pandemic: A systematic review of randomised controlled trials with meta-analysis.

This systematic review aims to investigate and determine the effectiveness of interventions on improving mental health (anxiety, depression, stress or mental well-being) and/or reducing burnout of nurses working in hospitals during the COVID-19 pandemic. A search was conducted on studies from conception to December 2022 in databases: PubMed, Embase, Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, Scopus and Web of Science and in ProQuest Thesis & Dissertations Global Database, Google Scholar and ClinicalTrials.gov. A total of 17 randomised controlled trials that evaluated different interventions were included. The outcomes were anxiety (n = 11), depression (n = 5), stress (n = 13) mental well-being (n = 7) and burnout (n = 7). Not all interventions led to positive outcomes. Grading of Recommendations Assessment, Development and Evaluation (GRADE) appraisal and risk of bias assessment using the Cochrane tool for randomised controlled trials (RoB 2.0) revealed poor quality of currently available literature, with low to very low certainty. Meta-analysis showed high heterogeneity among the five different outcomes, with subgroup analysis showing greater success in interventions conducted on nurses involved in the care of COVID-19 patients. More well-designed trials are necessary to reinforce current evidence to improve the mental health of nurses, to not only protect their quality of life but also to ensure the quality of patient care.

One-step photodeposition of spatially separated CuOx and MnOx dual cocatalysts on g-C3N4 for enhanced CO2 photoreduction.

The rapid recombination of photogenerated carriers of photocatalysts greatly limits their actual application in CO2 conversion into valuable chemicals. Herein, dual CuOx and MnOx cocatalysts are decorated on g-C3N4 nanosheets via a one-step photodeposition strategy. Benefiting from the repulsion between Cu2+ and Mn2+ cations, a novel g-C3N4-based heterostructure loaded with spatially separated CuOx and MnOx nanoparticle dual cocatalysts has been successfully fabricated. Cu favors the trapping of electrons, while MnOx tends to collect holes. Moreover, the Cu2O/g-C3N4 p-n heterojunction also accelerates the charge separation. As a result, the photogenerated holes and electrons flow into and out of the photocatalyst, respectively, resulting in enhanced charge separation for achieving efficient CO2 photoreduction over CuOx/g-C3N4/MnOx. Accordingly, the optimized CuOx/g-C3N4/MnOx exhibits an improved CO production rate of 5.49 µmol g-1 h-1, which is 27.5 times higher than that of bare g-C3N4.

Preparation of Gd-doped AuNBP@mSiO2 nanocomposites for the MR imaging, drug delivery and chemo-photothermal synergistic killing of breast cancer cells.

Under near-infrared (NIR) light, gold nanobipyramids (AuNBPs) exhibit a high photothermal conversion rate and photothermal stability, making them ideal mediators for photothermal therapy (PTT). In this study, highly purified AuNBPs are prepared, followed by coating their surfaces with mesoporous silica (mSiO2). The obtained AuNBP@mSiO2 nanocomplex exhibits an ellipsoidal shape with a relatively large specific surface, pore diameter and pore volume. To achieve MRI guided chemo-photothermal therapy of breast cancer cells, the nanocomplex is further coupled with the MRI contrast agent Gd-DTTA and the chemotherapeutic drug doxorubicin (DOX). The results indicated that under NIR light irradiation, AuNBPs exhibited promising PTT effects, while the cumulative release rate of DOX was significantly enhanced to 81.40%. Moreover, the chemo-photothermal therapy approach effectively eradicated 4T1 breast cancer cells. This work successfully confirms that chemo-photothermal synergistic therapy is an effective tumor treatment strategy and demonstrates the potential application of AuNBP@mSiO2 as a nano-drug delivery platform. Additionally, it introduces new ideas for the integrated study of breast cancer diagnosis and treatment.

Impact of COVID-19 on health of menopausal women: A scoping review.

OBJECTIVE: This scoping review aims to map and summarize the direct impact of contracting COVID-19, and the indirect consequences of the pandemic on the health of peri- and postmenopausal women. METHODS: Searches for published studies were conducted in CINAHL, Cochrane, EMBASE, PubMed, Scopus, Web of Science, PsycINFO and ProQuest from inception to 26 Oct, 2022. Grey literature and reference lists of included studies were searched. Results are presented as a narrative synthesis and tables. RESULTS: Thirty-eight studies were selected in this review. Overall, a majority of studies (n = 31) suggest that menopausal women were negatively impacted, while lesser studies (n = 21) concluded that they were not and some studies (n = 14) produced both negative and neutral results. Twenty-three studies presented on the direct health impact of COVID-19 infections on menopausal women. Eleven studies focused on the indirect impact of COVID-19 in terms of contact restriction measures on menopausal health during the pandemic compared to before the pandemic. Six studies described the different indirect impact of COVID-19 on health of menopausal women with various characteristics or lifestyles. CONCLUSION: The direct and indirect impacts of COVID-19 on menopausal women on physical, mental health and social wellbeing are largely negative.

[Mechanism of Xuebijing Injection in treatment of sepsis-associated ARDS based on network pharmacology and in vitro experiment].

The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1ß), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1ß, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.

Metal-free visible-induced C(sp2)-C(sp2) coupling of quinoxalin-2(H)-ones via oxidative cleavage of the C-N bond.

A C(sp2)-C(sp2) reaction between aromatic hydrazines and quinoxalines has been developed through a photocatalytic system. The protocol is established for C(sp2)-N bond cleavage and direct C(sp2)-H functionalization for the coupling of C(sp2)-C(sp2) via photocatalysis under mild and ideal air conditions without the presence of a strong base and metal. The mechanistic studies reveal that the generation of a benzene radical via the oxidative cleavage of aromatic hydrazines for the cross-coupling of C(sp2)-C(sp2) with the assistance of a photocatalyst is essential. The process exhibits excellent compatibility with functional groups and provides convenient access to various 3-arylquinoxalin-2(1H)-ones in good to excellent yields.

Asymmetric stem-loop-mediated isothermal amplification of nucleic acids for DNA diagnostic assays by simple modification of canonical PCR primers.

Nucleic acid-based assays have been adopted as mainstream tools for clinical diagnostics, food safety, and environment monitoring with the merits of accuracy, rapidity, and sensitivity. Loop-mediated isothermal amplification (LAMP) is a well-established method to rapidly identify nucleic acids and has gained recognition and been developed for clinical applications in resource-limited areas. However, the needs for specifically designed primer sets and non-specific amplification hinder the development of LAMP-based nucleic acid tests. Here, a promoted method, termed asymmetric stem-loop-mediated isothermal amplification (ASLAMP) by simple modification of canonical PCR primers, was developed to attempt to overcome those drawbacks. The two primers in the ASLAMP reaction can be easily obtained by adding a stem-loop sequence part to one PCR primer at 5'-ends to get the folding primer (FP), then adding the same primer to the counter canonical PCR primer at 5'-ends to get the turn-back primer (TP). The ASLAMP method was demonstrated in detecting the H1N1 gene fragment with merits of simple primer design, short target sequence, and high amplification efficiency. In addition, the ASLAMP method showed similar efficacy compared with LAMP targeting at the same H1N1 gene sequence. Furthermore, Shigella detection monitored by real-time fluorescence and endpoint colorimetric approaches were taken as examples for evaluation of the practical application of the ASLAMP method, both offered 100% sensitivity and specificity. In conclusion, the novel ASLAMP method with simplicity of primer design, low requirement of equipment, efficiency, and rapidity has exhibited its great prospect for establishment of DNA isothermal amplification in point of care application.

Closed dumbbell mediated isothermal amplification of nucleic acids for DNA diagnostic assays.

Nucleic acid amplification tests have been widely applied in clinical diagnostics, food safety monitoring, and molecular biology. As a well-established isothermal amplification method, Loop-mediated isothermal amplification (LAMP) has gained recognition. However, the need for specifically designed four to six primers and non-specific amplification pose challenges for further application of LAMP based detection methods. Here, a novel isothermal amplification method, termed closed dumbbell mediated isothermal amplification (CDA) of nucleic acids, was developed. The primers are easily designed by adding two different parts of middle sequence to the canonical PCR primers at 5'-ends. CDA method was demonstrated in detecting MERS-CoV orf1a gene and H1N1 gene fragments with merits of short core primer, simple primer design process and high amplification efficiency. In addition, CDA showed excellent amplification efficacy over LAMP and competitive annealing mediated isothermal amplification (CAMP) by slight modification of primers targeting at same sequence. Furthermore, real-time and HNB based colorimetric CDA detection of Shigella were developed for practical application, both exhibited 100% success. In all, the developed CDA method with high specificity, simplicity, efficiency and rapidity has shown its great potential for point of care nucleic acids diagnostic.

Serum VEGF-C as an evaluation marker of disease activity in adult-onset Still's disease.

In view of the possible involvement of vascular endothelial growth factor-C (VEGF-C) in pathogenesis of adult-onset Still's disease (AOSD) based on our previous genome-wide association study (GWAS) results, the primary objective of this study, therefore, was to investigate the correlations between the content of VEGF-C in serum and clinical and biochemical markers of AOSD. Blood samples were collected from 80 patients with AOSD, 26 with rheumatoid arthritis (RA), 30 with systemic lupus erythematosus (SLE) and 31 healthy control subjects. The serum VEGF-C levels were determined using an enzyme-linked immunosorbent assay (ELISA). Statistical analysis and comparisons were conducted. A significantly higher serum VEGF-C level was observed in patients with AOSD than in HC. Serum VEGF-C levels had high AUC value of 0.8145 for distinguishing AOSD group from healthy group with sensitivity of 0.7097 and specificity of 0.8250. It also showed good diagnostic value to differentiate AOSD from other autoinflammatory diseases with sensitivity of 0.7500 and specificity of 0.5500. AOSD patients with fever, arthralgia, skin rash, sore throat, lymphadenopathy, splenomegaly hepatomegaly and pleuritis, had a higher level than those who did not have these symptoms (p = 0.0012, p = 0.0092, p = 0.0056, p = 0.0123, p = 0.0068, p = 0.0030, p = 0.0020, and p = 0.0018, respectively). The serum VEGF-C levels were also positively correlated with laboratory features and several cytokines related to AOSD disease activity. In conclusion, our study unveiled a close association between serum VEGF-C levels and AOSD including disease activity and clinical hematological manifestations, suggesting the potential utility of VEGF-C as a candidate biomarker to assess disease activity in AOSD.

Prevalence and risk factors of sexual dysfunction in patients with inflammatory bowel disease: systematic review and meta-analysis.

PURPOSE: Sexual dysfunction (SD) is increasingly identified in patients with inflammatory bowel disease (IBD), but there are few systematic reviews and meta-analyses of the studies of SD in IBD patients. The purpose of the study is to further quantify the association between IBD and SD. METHODS: MEDLINE (OVID), EMBASE (OVID), and the Cochrane Library (OVID) were searched (until August 2020) to identify observational studies that reported the prevalence and risk factors of SD in IBD patients. Pooled prevalence, odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. RESULTS: Of the 945 citations evaluated, 18 studies (including 36,676 subjects) reporting the prevalence of SD in the IBD population were included for analysis. The overall pooled prevalence was 39% (95% CI 37-40%, P < 0.001). The prevalence of SD in women was 53% (95% CI 50-55%, P < 0.001), and it was 27% (95% CI 25-29%, P < 0.001) in men. The prevalence was higher in conjunction with operation (OR, 1.33, 95% CI 1.22-1.45, P < 0.001), depression (OR 6.14, 95% CI 3.51-10.76, P < 0.001), disease activity (OR 2.73, 95% CI 1.32-5.64, P = 0.007), comorbidities (OR 3.21, 95% CI 2.06-5.00, P < 0.001), age < 50 years (OR 3.85, 95% CI 2.41-6.14, P < 0.001), and the need for corticosteroids (OR 2.62, 95% CI 1.48-4.66, P = 0.001). CONCLUSION: SD occurred frequently in the IBD population. Operation, depression, disease activity, comorbidities, age < 50 years, and the need for corticosteroids were risk factors for SD in IBD patients. SD screening might be recommended in IBD patients with the aforementioned factors.

Characteristics and risk factors of relapses in patients with adult-onset Still's disease: a long-term cohort study.

OBJECTIVES: To describe the detailed characteristics and explore the potential risk factors of relapses in patients with adult-onset Still's disease (AOSD). METHODS: We enrolled patients with AOSD admitted to the Department of Rheumatology and Immunology, Ruijin Hospital from August 2016 to September 2019. Kaplan-Meier curves and the log rank test were used to estimate the cumulative relapse probability and persistent remission rate before the first occurrence of relapse. The multivariate Cox proportional hazard method was utilized to identify risk factors associated with relapses of AOSD. RESULTS: A total of 122 patients with AOSD were enrolled with a median follow-up of 12.6 months. Among them, 26 (21.3%) patients had at least one relapse. The cumulative relapse rates of AOSD patients were 14.42%, 21.79%, 24.81% and 28.57% at 6, 12, 18 and 36 months, respectively. According to the multivariate analysis, intensive treatment (odds ratio: 6.848; 95% CI: 2.441, 19.211) and macrophage activation syndrome (odds ratio: 4.020, 95% CI: 1.564, 10.322) were associated with increased risk of relapse. CONCLUSION: Our study indicated that relapses occurred in at least one-fifth of patients with AOSD, and patients with high disease severity at initial attack may have an increased risk of relapse, which needs more intensive therapy and close follow-up.

Pregnancy Outcomes in Patients With Adult-Onset Still's Disease: A Cohort Study From China.

Objective: Adult-onset Still's disease (AOSD) is an autoinflammatory disease with a higher prevalence rate in young females. The purpose of this study is to investigate whether AOSD has an adverse impact on pregnancy outcomes, or conversely exacerbated by pregnancy. Methods: The outcomes of 191 pregnancies were evaluated in 86 female patients with AOSD. The generalized linear mixed model and propensity score matching method were conducted to evaluate the influence of AOSD on pregnancy outcomes. A dependent sample sign test was applied to assess the impact of pregnancy on the relapse of AOSD. Results: The results showed that the post-AOSD group had a lower proportion of normal delivery (25.0 vs. 52.4%, p = 0.036) and a higher proportion of spontaneous abortion (STA) (18.8 vs. 0.6%, p = 0.002) compared with the pre-AOSD group. Moreover, pregnancy after being diagnosed with AOSD was a significant high risk factor of STA (adjusted OR = 4.577, 95% CI: 4.166-845.119; p = 0.003). Disease flare upon conception was observed in one of 16 post-AOSD pregnancies (p = 1.000). There were 11 patients with new-onset AOSD during gestation or postpartum, among which five (45.4%) evolved into the polycyclic course. Conclusions: AOSD patients might suffer from a higher risk of STA, however, pregnancy might not be related with the exacerbation of diagnosed AOSD. New-onset AOSD during gestation or postpartum tend to evolve into the polycyclic course.

Clinical features of Epstein-Barr virus in the intestinal mucosa and blood of patients with inflammatory bowel disease.

BACKGROUND: The role of Epstein-Barr virus (EBV) in inflammatory bowel disease (IBD) remains to be elucidated. The aim of this study was to investigate the presence of EBV in the blood and intestinal mucosa of patients with IBD and evaluate the association between EBV positivity and IBD. METHODS: Patients with IBD, hospitalized between January 2015 and April 2018, were enrolled. The EBV-DNA load in blood samples from each subject was analyzed by quantitative real-time polymerase chain reaction. EBV-encoded small-RNA 1 (EBER-1) was detected by in-situ hybridization in intestinal mucosa tissue sections of patients with IBD. RESULT: EBV-DNA was detected in 48 out of 568 patients with IBD (8.4%), and EBER-1 positivity was detected in 27 of these patients (56.3%). Refractory IBD and severe mucosal inflammation were more common in patients with detectable levels of EBER-1 than in those without; the number of EBER-1-positive cells positively correlated with mucosal inflammation (P value < 0.05). Age (≥60 years old) and use of azathioprine were risk factors for EBV infection. There was no significant difference in clinical remission rate and surgical rate between the EBER-1 positive group and EBER-1 negative group, antiviral group and the non-antiviral group, among IBD patients who tested positive for EBV-DNA. CONCLUSION: Elderly patients with IBD, treated with azathioprine, are more susceptible to EBV positivity. Further, EBV mucosal detection correlated with the severity of mucosal damage and refractoriness, but not prognosis.

Anxiety and depression in adult-onset Still's disease patients and associations with health-related quality of life.

OBJECTIVE: Adult-onset Still's disease (AOSD) is an autoinflammatory disorder leading to multiorgan involvements. We sought to investigate mood status and the health-related quality of life (HRQoL) in these patients. METHODS: In this study, 82 AOSD patients and 82 age- and sex-matched healthy controls were included. Demographic and clinical data of recruited patients were collected. The Hospital Anxiety and Depression Scale (HADS) and Medical Outcomes Survey Short Form-36 (SF-36) were used to evaluate the mood status and quality of life, respectively. Spearman correlation and multivariable linear regression analyses were used to assess the disease-related risk factors associated with anxiety and depression. RESULTS: Forty-four active and thirty-eight relieved patients were enrolled. We found that scores of both HADS anxiety (HADS-A) and depression (HADS-D) subscales in active AOSD were significantly higher than inactive patients, which were significantly higher than controls. Moreover, the HADS-A was positively correlated to the patient's global assessment (PGA), pain, and dosage of prednisone, and the HADS-D was positively correlated to systemic score, PGA, and pain. Female, high dosage of corticosteroids, and PGA more than 50 had a significant association with HADS-A score, while the sore throat and PGA more than 50 had a significant association with HADS-D score. Furthermore, AOSD patients' anxiety and depression had a negative impact on HRQoL. CONCLUSION: Active AOSD patients tended to be anxious and depressed, suffering from poorer HRQoL compared to patients in remission. Therefore, the evaluation of mental health and HRQoL should be included in AOSD patients' long-term management. Key Points • Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder leading to multiorgan involvement. This study was so far the first published research focuses on AOSD patients' mental involvement and health-related quality of life (HRQoL). • Active AOSD patients were more tended to be anxious and depressive and suffered from poorer HRQoL compared to inactive patients. • Patients' anxiety and depression were associated with impaired HRQoL.

Clinical performance of automated chemiluminescent methods for anticardiolipin and anti-ß2-glycoprotein I antibodies detection in a large cohort of Chinese patients with antiphospholipid syndrome.

INTRODUCTION: To assess the clinical performance and correlations of automated chemiluminescence assay (CIA) and enzyme-linked immunosorbent assay (ELISA) for detecting antiphospholipid (aPL) antibodies in the diagnosis of antiphospholipid syndrome (APS). METHODS: The study recruited 505 subjects, including 192 with APS, 193 with connective tissue diseases other than APS, and 120 healthy donors. We measured anticardiolipin (aCL) and anti-ß2-glycoprotein I (anti-ß2GPI) antibodies IgG, IgM, and IgA in all the samples using both CIA and ELISA. RESULTS: Total agreement between the two methods ranged from 83.50% for anti-ß2GPI IgG antibodies to 92.76% for anti-ß2GPI IgM antibodies in all the groups. Anti-ß2GPI and aCL IgG assays showed the highest Spearman's rho coefficients (anti-ß2GPI IgG = 0.742, aCL IgG = 0.715). Anti-ß2GPI IgG CIA showed the highest sensitivity for diagnosis of APS at 80.21%, which was significantly higher than the sensitivity of anti-ß2GPI IgG ELISA (52.08%). For diagnosis of APS, anti-ß2GPI IgG CIA had the best discrimination power with the area under the curves (AUC) of 0.922, followed by aCL IgG CIA (AUC of 0.905). While the CIA AUC was slightly higher in all cases, the difference was not statistically significant. CONCLUSION: CIA measurements had a good agreement and correlation with comparative ELISA assays. The CIA anti-ß2GPI IgG however was significantly more sensitive for APS diagnosis. The two assay methodologies showed comparable predictive powers and support the value of the CIA method for improved diagnosis and management of patients with APS.

A Cohort Study of Liver Involvement in Patients With Adult-Onset Still's Disease: Prevalence, Characteristics and Impact on Prognosis.

Objective: Adult-onset Still's disease (AOSD) is a systemic disorder commonly accompanied by liver involvement. This study aims to illustrate the detailed information of liver abnormalities in patients with AOSD and evaluate the impact on the prognosis. Methods: A total number of 128 hospitalized patients, who met the Yamaguchi criteria of AOSD in the Department of Rheumatology and Immunology, Ruijin Hospital from July 2016 to August 2019 were consecutively enrolled and followed up. The demographic characteristics, clinical features, laboratory tests, treatments and prognosis were recorded. Correlations of liver function tests (LFTs) with disease activity and laboratory parameters were analyzed by the Spearman test. Risk factors of the refractory AOSD were evaluated by multivariate logistic regression analysis. Results: Liver involvement was presented in 104 (81.3%) patients with AOSD. We observed that 34 (32.7%) patients were with mild elevation, 32 (30.8%) patients were with moderate elevation, and 38 (36.5%) patients were with severe elevation. The majority of elevated ALT, AST and ALP decreased to normal within the range of 2 months, except for GGT. Furthermore, the LFTs were found significantly correlated with disease activity. Besides, we found patients with higher levels of LFTs tended to require more intensive treatments and suffered from poorer prognosis. Multivariate logistic regression analysis showed ALP ≥ 141 IU/L and GGT ≥ 132 IU/L are independent risk factors of refractory AOSD. Conclusion: Liver involvement is common in patients with AOSD, the levels of LFTs are associated with disease activity and related to the treatment strategies and prognosis.

Increased neutrophil extracellular traps activate NLRP3 and inflammatory macrophages in adult-onset Still's disease.

BACKGROUND: Adult-onset Still's disease (AOSD) is a systemic inflammatory disease characterized by neutrophilia and NLRP3 inflammasome and macrophage activation. We investigated the role of neutrophil extracellular traps (NETs) in the pathogenesis of AOSD, and explored the effect of NETs on activating NLRP3 inflammasome and proinflammatory macrophages. METHODS: The sera of 73 AOSD patients and 40 healthy controls were used to detect the level of cell-free DNA and NET-DNA complexes. NET formation ex vivo was analyzed using immunofluorescence and flow plates. The activation of NLRP3 inflammasome in THP-1 cells and proinflammatory macrophages stimulated with DNA purified from NETs was measured using RT-PCR, ELISA, Western blotting and flow cytometry. RESULTS: The levels of cell-free DNA and NET-DNA complexes were significantly increased in the circulation of patients with AOSD compared with healthy controls, and freshly isolated neutrophils from patients with AOSD were predisposed to high levels of spontaneous NET release. Interestingly, enhanced NET release was abrogated with NADPH oxidase inhibitors and a mitochondrial scavenger. Furthermore, DNA purified from AOSD NETs activated NLRP3 inflammasomes. NET DNA from AOSD also exerted a potent capacity to accelerate the activation of CD68+CD86+ macrophages and increased the expression of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α. Finally, the copy number of mitochondrial DNA (mtDNA) in NETs and plasma was significantly increased in AOSD patients, suggesting that mtDNA may be involved in the activation of NLRP3 and inflammatory macrophages. CONCLUSIONS: These findings implicate accelerated NET formation in AOSD pathogenesis through activation of NLRP3 and proinflammatory macrophages, and identify a novel link between neutrophils and macrophages by NET formation in AOSD.

Causes of death in hospitalized patients with systemic lupus erythematosus: a 10-year multicenter nationwide Chinese cohort.

To estimate the mortality and describe the causes of death in a large multicenter cohort of hospitalized patients with SLE in China. This was a retrospective study of a nationwide SLE cohort (10 centers, 29,510 hospitalized patients) from 2005 to 2014 in China. Standardized mortality ratios (SMRs) were calculated for all death and were stratified by sex and age. Chi-square test was used to determine whether the major causes of death vary in age, sex, duration of SLE, disease activity, or medications. Comparison between dead patients and survival controls was used to identify the risk factors for mortality. Logistic regression analysis was used to evaluate the risk factors for mortality. A total of 360 patients died during the study period, accounting for 1.22%. The overall SMR was 2.13 (95% CI 1.96, 2.30), with a particularly high SMR seen in subgroups characterized by younger age. Infection (65.8%) was the most common cause of death, followed by lupus nephritis (48.6%), hematological abnormality (18.1%), neuropsychiatric lupus/NPSLE (15.8%), and interstitial pneumonia (13.1%). Cardiovascular disease and malignancy contributed little to the causes of death. Infection, in particular severe pulmonary infection, emerged as the foremost risk factor for mortality, followed by lupus encephalopathy. However, lupus nephritis and hematological abnormalities occurred more frequently in survival patients. SLE patients at a younger age of diagnosis have a poorer prognosis. Infection dominated the causes of death in recent China. Ethnicity and medications might account for the differences in causes of death compared with western populations.