Multi-petawatt laser facility fully based on optical parametric chirped-pulse amplification.

We report on a multi-petawatt 3-cascaded all-optical parametric chirped-pulse amplification laser facility. The experimental results demonstrate that the maximum energy after the final amplifier and after the compressor is 168.7 J and 91.1 J, respectively. The pulse width (FWHM) is 18.6 fs in full width at half maximum after optimization of pulse compression. Therefore, 4.9 PW peak power has been achieved for the laser facility. To the best of our knowledge, this is the highest peak power reported so far for an all-optical parametric chirped-pulse amplification facility, and a compressed pulse shorter than 20 fs is achieved in a PW-class laser facility for the first time.

The Efficacy of Imrecoxib and Celecoxib in Axial Spondyloarthritis and Their Influence on Serum Dickopff-Related Protein 1 (DKK-1) Levels.

BACKGROUND To observe and demonstrate therapeutic effects and side effects of two selective COX-2 inhibitors, imrecoxib and celecoxib, on patients with axial spondyloarthritis (axSpA) and observe the correlation between imaging scores and serum DKK-1 levels. MATERIAL AND METHODS Sixty patients with axSpA were randomly assigned to receive 200 mg imrecoxib or 200 mg celecoxib twice daily. Fifty-one patients who completed follow-up were included in the study. At baseline, week 4, and week 12, the clinical parameters, inflammatory markers (ESR, CRP), and adverse reactions were recorded. Serum DKK-1 levels were investigated by enzyme-linked immunosorbent assay. Radiographic scores were calculated by sacroiliac joint SPARCC (Spondyloarthritis Research Consortium of Canada) score method at baseline serum DKK-1 levels and week 12. RESULTS Patients in the imrecoxib group (n=25) and patients in the celecoxib group (n=26) were improved at week 4. At week 12, all clinical parameters and inflammatory markers were improved in the two groups and the differences was not statistically significant. Serum DKK-1 levels were decreased and the differences were not statistically significant. Serum DKK-1 levels in patients in the imrecoxib group at baseline were negatively correlated with all study parameters, while those in the celecoxib group had correlations with BASFI (r=-0.048, p=0.027) and Schober test (r=0.437, p=0.048), without any correlation with other clinical parameters or inflammatory markers. CONCLUSIONS Patients experienced significant improvement in disease activity, functional parameters, and inflammatory markers when treated with selective COX-2 inhibitors for 12 weeks, and the efficacy of imrecoxib was not inferior to celecoxib. Selective COX-2 inhibitors imrecoxib and celecoxib had no obvious effects on serum DKK-1 levels.

Design and optimization of the seed pulse generation scheme for precise beam synchronization in the Xingguang-III laser.

Xingguang-III is a large hybrid optical parametric amplification/chirped pulse amplification laser that outputs synchronized femtosecond, picosecond, and nanosecond beams with three different wavelengths, i.e., 800, 1053, and 527 nm, respectively. We present here an in-house front-end system design that generates the 1053 nm seed laser for the ps/ns beam directly from the 800 nm femtosecond laser, which enables the three beams to have intrinsic synchronization. The results show that a seed laser of 140 µJ energy and 1053 nm central wavelength with 34 nm spectral width (FWHM) is generated and the shot-to-shot timing jitter (peak-to-valley) between the fs and the ps beam is less than 1.32 ps.

Dynamic monitoring of UBA1 somatic mutations in patients with relapsing polychondritis.

BACKGROUND: Commonly clinically diagnosed with relapsing polychondritis (RP), vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS) is a recently identified autoinflammatory disease caused by UBA1 somatic mutations. The low frequency and dynamic changes challenge the accurate detection of somatic mutations. The present study monitored these mutations in Chinese patients with RP. We included 44 patients with RP. Sanger sequencing of UBA1 was performed using genomic DNA from peripheral blood. Droplet digital polymerase chain reaction (ddPCR) was performed to screen low-prevalence somatic variants. RESULTS: Multiple ddPCR detections were performed using available blood samples collected at different follow-up time points. Three male patients were UBA1 somatic mutation carriers. Sanger sequencing detected the somatic UBA1 variant c.122T > C (p.Met41Thr) in two male patients. Initial ddPCR confirmed the variant in the two patients, with allele fractions of 73.75% and 88.46%, respectively, while yielding negative results in other patients. Subsequent ddPCR detected the somatic variant (c.122T > C) with low prevalence (1.02%) in another male patient from blood samples collected at a different time point, and confirmed dynamically fractional abundance in one patient with VEXAS, with allele fractions of 73.75%, 61.28%, 65.01%, and 73.75%. Nine patients assessed by ddPCR at different time points remained negative. CONCLUSION: We report UBA1 variants in patients with RP in the Chinese population for the first time. Multiple ddPCR detections from samples collected at different time points can enhance sensitivity and should be considered for patients with initial negative ddPCR results.

Imrecoxib and celecoxib affect sacroiliac joint inflammation in axSpA by regulating bone metabolism and angiogenesis.

OBJECTIVE: To analyze the changes in the levels of bone metabolism markers related to sacroiliac joint (SIJ) inflammation in patients with axial spondyloarthritis (axSpA) after treatment with imrecoxib and celecoxib and evaluate their relationship with clinical efficacy. METHODS: A total of 120 patients with axSpA with at least 2 magnetic resonance imaging (MRI) SIJ scans during a 12-week follow-up were enrolled. The levels of bone metabolism markers, including dickkopf-1(DKK-1), sclerostin, vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2), osteoprotegerin (OPG), noggin, ß-catenin, and RUNX2, were measured twice, and their association with disease activity and the Spondyloarthritis Research Consortium of Canada (SPARCC) score for SIJ were analyzed by univariate analysis of covariance. RESULTS: A total of 116 patients completed the follow-up. The levels of sclerostin, OPG, noggin, DKK-1, and RUNX2 were increased, whereas those of VEGF and ß-catenin were decreased. The levels of sclerostin and OPG were negatively correlated with disease duration. The levels of VEGF and ß-catenin were significantly decreased (F = 7.866, P = 0.003; F = 4.106, P = 0.047) in patients with disease remission. A decrease in ESR was significantly correlated with decreased levels of Runx2 and SPARCC scores, with the levels of sclerostin being significantly elevated in the SPARCC-reduced group. There were no statistically significant differences between the imrecoxib and celecoxib groups (P> 0.05). CONCLUSION: Imrecoxib and celecoxib affect SIJ inflammation, disease activity, and the course of disease by regulating bone metabolism and angiogenesis in axSpA. Key Points •After treatment with imrecoxib and celecoxib, the levels of sclerostin, OPG, noggin, DKK-1, and RUNX2 were increased, whereas those of VEGF and ß-catenin were decreased, correlating with the course of disease, disease activity, and SIJ inflammation. • A decrease in ESR was significantly correlated with a decrease in the levels of RUNX2 and SIJ inflammation.. • The levels of sclerostin were more significantly elevated in SIJ inflammation remission group.. •Imrecoxib and celecoxib affect SIJ inflammation by regulating bone metabolism and angiogenesis in axSpA..

Evaluation of red blood cell distribution width-platelet ratio as a predictor of adverse pregnancy outcomes and disease severity in systemic lupus erythematosus.

OBJECTIVE: The red blood cell distribution width to platelet ratio (RPR) is known to reflect systemic inflammation. This study aimed to explore the predictive value of RPR for disease activity and adverse pregnancy outcomes (APOs) in pregnant women with systemic lupus erythematosus (SLE). METHODS: We retrospectively evaluated case data of all pregnant women with SLE managed at the First Affiliated Hospital of Zhengzhou University from January 2014 to March 2017. Correlations between RPR and SLE clinical disease activity, organ involvement, and maternal complications were analysed. Changes in the RPR and erythrocyte sedimentation rate (ESR) were observed before and after treatment. A receiver operating characteristic (ROC) curve was used to predict disease activity and APOs based on RPR. RESULTS: A total of 118 patients were enrolled, including 77 in the disease-active group and 41 in the disease-inactive group. The live birth rate was significantly higher in the disease-inactive group than in the disease-active group (P < 0.001). Compared to the disease-inactive group, the number of patients with elevated RPR, anti-dsDNA antibody level, and ESR was significantly higher in the disease-active group, whereas their platelet-lymphocyte ratios and complement 3 and 4 levels were significantly lower. The disease-active group was more likely to experience APOs (P < 0.001), mainly due to premature birth, low birth weight, and pregnancy loss. The ROC curve indicated that RPR had an effect on disease activity and APOs. CONCLUSION: RPR can be used as a predictor of disease severity and APOs in pregnant women with SLE. Key Points • RPR positively correlated with SLEDAI; patients with elevated RPR have higher disease activity, more organ, and more maternal complications. • Monitoring RPR could better predict disease activity in pregnant patients with SLE and reduce the incidence of maternal complications and APOs.

Clinical features of new-onset systemic lupus erythematosus during pregnancy in Central China: a retrospective study of 68 pregnancies.

The aim of this study is to explore the clinical features and pregnancy outcomes of Chinese patients with new-onset systemic lupus erythematosus (SLE) during pregnancy or puerperium. We retrospectively evaluated the data of all pregnant women with SLE managed at the First Affiliated Hospital of Zhengzhou University between April 2013 and March 2017. Clinical characteristics, laboratory features, medication use, and pregnancy outcomes were compared between pregnant women with new-onset SLE and pregnant women with pre-existing SLE. Risk factors for adverse pregnancy outcomes were determined using binary regression analyses. Overall, 223 pregnancies in 216 patients were included; 148 (69.6%) patients had a history of SLE, and 68 (30.4%) were diagnosed with SLE during pregnancy or puerperium. Most cases of new-onset SLE (72.1%) occurred during the first and second trimesters. Thrombocytopaenia (especially severe thrombocytopaenia) (76.5% vs 54.2%, P = 0.008; 39.7% vs 15.5%, P = 0.001) and anaemia (especially moderate anaemia) (73.5% vs 56.9%, P = 0.007; 52.9% vs 35.2%, P = 0.035) were more common in women with new-onset SLE than in women with pre-existing SLE and active disease during pregnancy. Additionally, patients with new-onset SLE experienced higher rates of moderate-to-severe disease activity than patients with pre-existing SLE (P < 0.01); disease activity occurred mostly during the first and second trimesters (75.4%). Compared with pre-existing SLE patients, disease activity in new-onset SLE patients occurred mostly in the first trimester (33.3% vs 15.3%, P = 0.043) and less in the third trimester (21.1% vs 47.2%, P < 0.001). Pregnancy loss was significantly higher in patients with new-onset SLE than in patients with pre-existing SLE (62.4% vs 27.1%, P < 0.001), with most cases occurring during the first and second trimesters (95.3%). However, there were no significant differences in neonatal outcomes between new-onset and pre-existing SLE patients with active disease. Within the new-onset SLE group, active disease was an independent risk factor for pregnancy loss (odds ratio [OR] = 16.185, confidence interval [CI] = 1.895-138.232, P = 0.011), whereas disease onset at late gestation was a protective factor against pregnancy loss (OR = 0.589, CI = 0.435-0.796, P = 0.013). Patients with new-onset SLE suffered greater haematological involvement (mainly thrombocytopaenia and anaemia) and higher rates of moderate-to-severe disease activity and pregnancy loss than patients with pre-existing SLE. Controlling disease activity and extending gestational age may improve pregnancy outcomes in women with new-onset SLE. Key Points • The clinical features of new-onset SLE during pregnancy and its impact on pregnancy outcomes have rarely been reported, especially in Chinese patients. • New-onset SLE during pregnancy in Chinese women occurred primarily during the first and second trimesters and was characterised by haematological disorders, including thrombocytopaenia and anaemia. • Women with new-onset SLE during pregnancy had significantly higher disease activity scores and pregnancy loss rates than women with pre-existing SLE, especially during the first and second trimesters; controlling disease activity and prolonging gestational age may improve pregnancy outcomes in this setting.

Blau syndrome with good Reponses to Tocilizumab: A case report and focused literature review.

OBJECTIVES: Blau syndrome (BS), a rare auto-inflammatory granulomatous disease, is a progressive disorder. Usually the maintenance dose of glucocorticoid may not be tapered below 15 mg per day while immunosuppressives is used. There has been some experience with biologic agents in refractory BS patients. The objective of this study is to describe the case of a BS patient benefiting from Tocilizumab, a humanized monoclonal antibody against interleukin 6 receptor. METHODS: We report the first Chinese patient with BS who was resistant to currently available therapies but had rapid quiescence after using Tocilizumab. We also conducted a systematic literature review about the current treatments of BS. RESULTS: A 13-year-old Chinese boy with BS, whose uveitis got worsened when treated with Infliximab, was well-controlled after taking Tocilizumab and prednisone was tapered off to a dose of 8mg per day. We identified 29 manuscripts providing 45 BS cases. Among these patients, 24 underwent biological treatments and 22 of them recovered. In these 29 manuscripts, the biological agents used to treat refractory BS included Etanercept, Infliximab, Adalimumab, Canakinumab and Anakinra. CONCLUSIONS: Case reports on the use of biological agents have yielded mixed results. The diversity of the symptoms may be due to functional differences in NOD2 mutations. For BS patients with fever, lymphadenopathy and hepatosplenomegaly, Tocilizumab may be a better choice.