Spatiotemporal characteristics and driving forces of terrorist attacks in Belt and Road regions.

To achieve the strategic goals of the Belt and Road Initiative (BRI), it is necessary to deepen our understanding of terrorist attacks in BRI countries. First, we selected data for terrorist attacks in BRI regions from 1998 to 2017 from the Global Terrorism Database and analyzed their time distribution using trend analysis and wavelet analysis. Then, we used honeycomb hexagons to present the spatial distribution characteristics. Finally, based on the Fragile States Index, we used GeoDetector to analyze the driving forces of the terrorist attacks. The following conclusions were obtained: (1) During 1998-2017, the number of events was the highest on Mondays and the lowest on Fridays. In addition, the incidence of events was high between Monday and Thursday but was the lowest on Fridays and Saturdays. The number of events was the largest in January, May, July, and November and was the lowest in June and September; the incidence of terrorist attacks from April to May and July to August was high. (2) Terrorist attacks showed a 10-year cycle during the study period. Terrorist attacks in the last 10 years of the study period were broader in scope and higher in number compared with the previous 10 years. In addition, China, Russia, Saudi Arabia, and northeastern Europe saw many new terrorist attacks during the latter 10 years. (3) The number of terrorist attacks by bombing/explosion was the largest, followed by armed attack; assassination, kidnapping, and infrastructure attacks were the least frequent. The core areas of the terrorist attacks were Iraq, Israel, Afghanistan, Pakistan, and India. (4) The driving force analysis revealed that the indicators "security apparatus," "human flight and brain drain," and "external intervention" contributed the most to BRI terrorist attacks.

Novel biomarkers containing citrullinated peptides for diagnosis of systemic lupus erythematosus using protein microarrays.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterised by autoantibody production. This study aims to identify biomarkers involving citrullinated peptides that can be used for SLE diagnosis. METHODS: After a negative selection step with serum from healthy controls (HCs), a phage library of 12 peptides was used for three rounds of screening with sera from 30 SLE patients. After four rounds of biopanning, 21 positive peptides were sequenced. We produced 37-feature arrays containing 16 recombinant citrullinated peptides. The microarrays were tested with an independent validation set of serum samples from 50 HCs, 60 SLE patients, and 60 rheumatoid arthritis (RA) patients. RESULTS: Microarray analysis showed that the positive rates of 13S1212Cit3-IgM (60.0%), 13S1210-IgG (43.33%), and 13S1212Cit3-IgG (41.67%) were increased in SLE patients compared with HCs and RA patients. The area under the receiver operating characteristic curve (AUC) was 0.770, 0.687 and 0.698, respectively. The combination of 13S1212Cit3-IgM and 13S1210-IgG (termed COPSLE, for combination of peptides for SLE) was more efficient for SLE diagnosis, with a larger AUC (0.830) and a positive rate of 73.33%. COPSLE could be used to identify 80.0% of SLE patients who were negative for anti-Smith (Sm), anti-double-stranded DNA (ds-DNA), and anticardiolipin (ACA). The Spearman rank correlation indicated that COPSLE increased with albumin, serum level of C3 and platelet distribution width, but had negative correlations with decreased C3 and discoid lupus. CONCLUSIONS: A citrullinated/non-citrullinated peptide panel is a valuable diagnostic marker of SLE, even for patients who are negative for anti-Sm, anti-ds-DNA and ACA.

Anti-ß2GPI/ß2GPI induces human neutrophils to generate NETs by relying on ROS.

Neutrophils participate in the regulation of pathogens by phagocytosis as well as by generating neutrophil extracellular traps (NETs). Antiphospholipid antibodies, particularly those targeting beta-2-glycoprotein I (ß2GPI), stimulate monocytes, platelets, and endothelial cells with prothrombotic participation. This study aimed to explore NET generation in response to anti-ß2GPI/ß2GPI. A series of experiments involving the separation of primary human leukocytes, NETosis quantification using propidium iodide, exploration of NETosis by fluorescence microscopy, western blotting, examination of free Zn2+ using FluoZin-3, and reactive oxygen species (ROS) examination with dihydrorhodamine 123 were performed in this study. We found that anti-ß2GPI/ß2GPI triggered NETosis, resembling phorbol 12-myristate 13-acetate (PMA)-induced NETosis in magnitude and morphology. The anti-ß2 GPI/ß2 GPI complex in isolation stimulated NETs without relying on p38, protein kinase B (AKT), extracellular signal-related kinase (ERK) 1/2, and zinc signals. NET generation was unaffected by the NADPH oxidase suppressor DP1. The anti-ß2 GPI/ß2 GPI complex stimulated ROS generation without relying on NADPH oxidase, which may participate in NET generation triggered via the anti-ß2 GPI/ß2 GPI complex. In summary, our results indicate that the anti-ß2 GPI/ß2 GPI complex reinforced NET generation by relying on ROS. THE SIGNIFICANCE OF THE PAPER IN THE CONTEXT OF CURRENT KNOWLEDGE: Neutrophils as one of the first lines of defence and essential in the response to pathogen invasion. They eradicate bacteria via phagocytosis or by releasing antimicrobial proteins in degranulation. In this study, we explored the capability of anti-ß2 GPI/ß2 GPI to stimulate NETosis, demonstrating that anti-ß2 GPI/ß2 GPI is a promising method for triggering NET. Anti-ß2 GPI/ß2 GPI induced ROS generation without relying on NADPH oxidase, which contributes to NETosis independently of ERK1/2, Zn2+ , or AKT. Our results showed that anti-ß2GPI/ß2GPI triggered NETosis, resembling PMA-induced NETosis in magnitude as well as morphology. The anti-ß2 GPI/ß2 GPI complex in isolation stimulated NETs without relying on p38, AKT, ERK1/2, or zinc signals. The anti-ß2 GPI/ß2 GPI complex stimulated ROS generation without relying on NADPH oxidase, which may participate in NET generation triggered via the anti-ß2 GPI/ß2 GPI complex.

Modeling using clinical examination indicators predicts interstitial lung disease among patients with rheumatoid arthritis.

Interstitial lung disease (ILD) is a severe extra-articular manifestation of rheumatoid arthritis (RA) that is well-defined as a chronic systemic autoimmune disease. A proportion of patients with RA-associated ILD (RA-ILD) develop pulmonary fibrosis (PF), resulting in poor prognosis and increased lifetime risk. We investigated whether routine clinical examination indicators (CEIs) could be used to identify RA patients with high PF risk. A total of 533 patients with established RA were recruited in this study for model building and 32 CEIs were measured for each of them. To identify PF risk, a new artificial neural network (ANN) was built, in which inputs were generated by calculating Euclidean distance of CEIs between patients. Receiver operating characteristic curve analysis indicated that the ANN performed well in predicting the PF risk (Youden index = 0.436) by only incorporating four CEIs including age, eosinophil count, platelet count, and white blood cell count. A set of 218 RA patients with healthy lungs or suffering from ILD and a set of 87 RA patients suffering from PF were used for independent validation. Results showed that the model successfully identified ILD and PF with a true positive rate of 84.9% and 82.8%, respectively. The present study suggests that model integration of multiple routine CEIs contributes to identification of potential PF risk among patients with RA.

Diagnostic value of anti-cyclic citrullinated peptide antibody for rheumatoid arthritis in a Chinese population: a meta-analysis.

To use meta-analysis to determine the accuracy of anti-cyclic citrullinated peptide (CCP) antibody in diagnosis of patients with rheumatoid arthritis (RA) in a Chinese population, we searched MEDLINE and CNKI databases for studies published in English or Chinese between January 2000 and June 2010. Two investigators independently evaluated studies for inclusion, data extraction, and quality assessment. We used a random-effects model to combine estimates of sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR). One hundred and eighteen studies met our inclusion criteria. All studies were of high quality. The summary estimates for anti-CCP antibody in the diagnosis of RA in a Chinese population were as follows: sensitivity 0.65 (95% confidence interval (CI) 0.65-0.66), specificity 0.95 (95% CI 0.95-0.96), positive likelihood ratio (LR+) 15.84 (95% CI 13.55-18.54), negative likelihood ratio (LR-) 0.33 (95% CI 0.31-0.35), and diagnostic odds ratio (DOR) 51.60 (95% CI 43.64-61.01). With high specificity and moderate sensitivity, anti-CCP antibody tests play an important role in conforming the diagnosis of RA in a Chinese population.

Anti-C1q antibodies are associated with systemic lupus erythematosus disease activity and lupus nephritis in northeast of China.

This study aimed to investigate the associations of anti-C1q antibodies with systemic lupus erythematosus (SLE) disease activity and lupus nephritis (LN) in northeast of China. Ninety patients with SLE, 37 patients with other autoimmune diseases, and 40 healthy donors in northeast of China were enrolled. Serum anti-C1q antibodies were measured by ELISA with 20 RU/ml as the threshold of positive results. The prevalence and levels of anti-C1q antibodies in SLE group (50%, 20.54 ± 34.67 RU/ml) were significantly higher than those in autoimmune disease and healthy control groups (P < 0.05), yet no significant difference between LN patients and non-LN lupus patients (57.14% vs 41.46%, P > 0.05; 25.92 ± 39.94 vs 13.07 ± 27.39 RU/ml, P > 0.05). Anti-C1q antibody levels were positively correlated with levels of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, anti-dsDNA, and anti-cardiolipin and negatively correlated with serum C3 and C4 (P < 0.05). The prevalence of anti-Sm and anti-nucleosome increased in anti-C1q-positive lupus patients (P < 0.05). Compared with anti-C1q-negative lupus patients, patients with 20-40 RU/ml anti-C1q antibodies had comparable disease activity (P > 0.05); patients with 40-80 RU/ml anti-C1q antibodies had significantly lower levels of serum complement (P < 0.05); patients with above 80 RU/ml anti-C1q antibodies had much more severe hypocomplementemia, increased SLEDAI scores, and higher incidence of hematuria and proteinuria (P < 0.05). Furthermore, the specificity and positive predictive value of 80 RU/ml anti-C1q antibodies for LN was 97.56% and 87.50%, respectively. In conclusion, anti-C1q antibodies are associated with SLE and LN disease activity, and the contribution hinges on the titers. Moreover, high-level anti-C1q antibodies are valuable for diagnosing LN.

Diagnostic value of anti-cyclic citrullinated peptide antibodies in northern Chinese Han patients with rheumatoid arthritis and its correlation with disease activity.

This study was to evaluate the diagnostic value of anti-cyclic citrullinated peptide (CCP) antibodies in northern Chinese Han patients with rheumatoid arthritis (RA) and its correlation with disease activity. Clinical data and serum samples were collected from 112 RA patients and 55 non-RA patients. Statistical analyses of the correlations among anti-CCP antibodies, other serological markers, and the RA patients' clinical characteristics were performed using SPSS 11.5 software. Anti-CCP antibodies were detected in 77.7% of all RA patients and 80.4% of the RA patients with a disease duration of 3 years or less. The combined diagnosis using high titer anti-CCP antibodies (>or=100 RU/ml) with a concomitant positive rheumatoid factor (RF) test exhibited the greatest diagnostic specificity; it achieved 87.9% for all RA patients and 90.1% for the patients with disease duration of three years or less. Moreover, anti-CCP antibodies showed medium correlations to the RA patient's serum RF titer (r = 0.560, P < 0.001) and disease activity (DAS28 score; r = 0.404, P < 0.001). Compared with the patients with low anti-CCP antibody titers (<100 RU/ml), patients with high anti-CCP antibody titers showed higher RF titers, worse DAS28 scores, and severe morning stiffness (P < 0.01). This study suggests that anti-CCP antibodies can be used for RA diagnosis and disease activity evaluation for northern Han Chinese patients. A combined diagnosis using both high titers of anti-CCP antibodies (>or=100 RU/ml) and a positive RF test markedly improves RA diagnostic specificity. Patients' DAS28 scores rise and morning stiffness intensifies with increasing anti-CCP antibody titers.