Study on the Heterogeneous Nucleation Mechanism of SiCp/AZ91 Magnesium Matrix Composites under Pulse Current.

SiCp/AZ91D magnesium matrix composites with 30% SiCp were successfully prepared by pulsed current melting in this work. Then, the influences of the pulse current on the microstructure, phase composition, and heterogeneous nucleation of the experimental materials were analyzed in detail. The results show that the grain size of both the solidification matrix structure and SiC reinforcement are refined by pulse current treatment, and the refining effect is gradually more obvious with an increase in the pulse current peak value. Moreover, the pulse current reduces the chemical potential of the reaction between SiCp and Mg matrix, thus promoting the reaction between SiCp and the alloy melt and stimulating the formation of Al4C3 along the grain boundaries. Furthermore, Al4C3 and MgO, as heterogeneous nucleation substrates, can induce heterogeneous nucleation and refine the solidification matrix structure. Finally, when increasing the peak value of the pulse current, the repulsive force between the particles increases while the agglomeration phenomenon is suppressed, which results in the dispersed distribution of SiC reinforcements.

Spinal and sacroiliac involvement in SAPHO syndrome: A single center study of a cohort of 354 patients.

OBJECTIVE: SAPHO syndrome is a highly heterogeneous disease with distinct treatment response. We report the largest cohort of SAPHO syndrome and explore its clinical classification with special interest in spinal and sacroiliac involvement. METHODS: A total of 354 patients with SAPHO syndrome were recruited in Peking Union Medical College Hospital. The demographic, clinical and imaging data were collected at baseline. Spinal and sacroiliac involvement was determined by the co-existence of related symptoms and imaging evidence of lesions in the spine or sacroiliac joints on either bone scintigraphy, CT or MRI. RESULTS: A total of 197 (55.6%) patients were identified to have spinal or sacroiliac involvement. Compared to those without spinal or sacroiliac lesions, these patients were significantly older at onset (38 ±â€¯12 vs 35 ±â€¯10 years old, p = 0.019) but had comparable duration of disease. Therapeutically, patients with spinal or sacroiliac involvement had been treated more aggressively with more frequently prescribed NSAIDs, glucocorticoids, DMARDs, TNF-α inhibitors, and bisphosphonates (all p ≤ 0.001). Nonetheless, greater disease activity was observed for these patients at baseline, supported by both inflammatory markers (ESR and hs-CRP) and visual analog scale (VAS) for pain (all p < 0.001). CONCLUSIONS: SAPHO patients with spinal or sacroiliac involvement are older at onset and have greater disease activity despite of more aggressive treatments compared to those without. Stratified management is in urgent need for this rare disease.

Efficacy of bisphosphonates in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: a prospective open study.

OBJECTIVES: To evaluate the clinical efficacy of bisphosphonates treatment for spinal bone marrow oedema (BME) in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. METHODS: SAPHO syndrome patients presenting to Peking Union Medical College Hospital from 2015 to 2016 were recruited. Patients were administered pamidronate disodium 1 mg/kg/d intravenously, for 3 days, at baseline and 3 months later. The symptoms were evaluated using the Visual Analog Score (VAS) for pain, and other clinical measures including, spinal BME scores, ß-crosslaps, osteocalcin, and inflammatory factors, were collected. RESULTS: A total of 30 patients (20 women and 10 men) with a median age of 47.2 (interquartile range 8.8) years were recruited. In a short time, the patients showed a significant decrease in VAS (before vs. after; first treatment: 5.70±1.62 vs. 2.30±1.29 cm, second treatment: 4.03±1.88 vs. 2.17±1.23 cm) and ß-crosslaps (first treatment: 0.4441±0.1923 vs. 0.0859±0.0374 pg/ml, second treatment: 0.2891±0.1983 vs. 0.0962±0.0324 pg/ml) (all p<0.05). At 12-month follow-up, compared with the baseline, we noticed a significant drop in the VAS (5.70±1.62 vs. 2.43±1.25 cm), erythrocyte sedimentation rate (28.87±25.26 vs. 18.00±18.65 mm/h), high-sensitivity C-reactive protein level (11.76±10.19 vs. 5.84±5.88 mg/L), osteocalcin (2.30±1.27 vs. 1.65±0.80 ng/ml), and BME (30.50±24.09 vs. 22.13±27.79) (all p<0.05). No one had serious adverse events. CONCLUSIONS: Bisphosphonates can significantly and rapidly relieve symptoms in patients with SAPHO syndrome and have a long-term effect on inflammation and spinal BME. We suggest that bisphosphonates could be used as the first-line therapeutic drug for SAPHO syndrome, especially in patients with spinal BME.

Three patterns of osteoarticular involvement in SAPHO syndrome: a cluster analysis based on whole body bone scintigraphy of 157 patients.

OBJECTIVES: To explore the patterns of osteoarticular involvement in SAPHO syndrome. METHODS: Baseline clinical characteristics and imaging data of 99mTc-MDP whole-body bone scintigraphy (WBBS) were collected from 157 out of 164 patients diagnosed with SAPHO syndrome. The twelve most frequently involved osteoarticular sites were analysed by hierarchical cluster analysis with the Ward minimum-variance method. RESULTS: Three distinctive patterns of osteoarticular involvement were identified: the spinal type (70 patients, 44.6%), with predominantly thoracic, lumbar or sacral vertebral lesions; the costal type (52 patients, 33.1%), with lesions of anterior ribs, particularly the first ribs; and the sternoclavicular type (35 patients, 22.3%), with predominantly sternal and bilateral sternoclavicular lesions, characterized by the typical bullhead sign. Notably, a total of 77 (49%) patients exhibited lesions of ribs on WBBS, of which 61.3% involved the first ribs. Interestingly, patients of spinal type were older at onset of cutaneous manifestations than those of sternoclavicular type (P = 0.036) and costal type (P = 0.035). The disease course was remarkably longer in sternoclavicular type than costal type (P = 0.001) and spinal type (P < 0.001). CONCLUSION: The osteoarticular involvement in SAPHO syndrome can be categorized as three distinct patterns with different corresponding clinical features. The costal involvement in SAPHO syndrome, which was under-recognized previously, may define a distinct sub-type of the disease.

Failure of tocilizumab in treating two patients with refractory SAPHO syndrome: a case report.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoinflammatory disease with no standard treatment. Interleukin (IL)-6 inhibitors represent a novel therapeutic option for rheumatoid arthritis and some autoinflammatory diseases. However, the clinical utility of IL-6 inhibitors in treating SAPHO syndrome has been poorly investigated. In the present report, we describe two patients with SAPHO syndrome that was unresponsive to conventional treatment. Tocilizumab, an anti-IL-6 receptor monoclonal antibody, was putatively administered according to positive IL-6 immunohistochemical staining in biopsied bone tissues. However, the disease continued to progress, and new-onset or worsening skin lesions were noted with transient neutropenia. These cases demonstrate that tocilizumab may not be an ideal option for treating SAPHO syndrome.

Case report: successful treatment of refractory SAPHO syndrome with the JAK inhibitor tofacitinib.

INTRODUCTION: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is an autoinflammatory disorder without standardized treatment. Janus kinase (JAK) inhibitors can block a range of cytokines and might possess significant anti-inflammatory activity. Here, we report the first case of efficacious treatment of refractory SAPHO syndrome with the JAK inhibitor tofacitinib. CASE PRESENTATION: A 44-year-old woman presented with arthralgia in the right wrist and complained of having difficulty in doing housework. Symptoms were unresponsiveness to nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and tumor necrosis factor inhibitors. A diagnosis of SAPHO syndrome was made based on previous dermatological and osteoarticular manifestations and bone scintigraphy findings. Oral treatment with tofacitinib at 5 mg twice daily in combination with the basic methotrexate treatment was initiated. After 4 weeks of using tofacitinib, the patient reported marked improvement of symptoms and also reported being competent in completing housework. CONCLUSIONS: The efficacy of JAK inhibitors in treating refractory SAPHO syndrome should be noted.

Advances in Mouse Models of Sjögren's Syndrome.

Sjögren's syndrome (SS) is a common chronic systemic autoimmune disease;however,its pathogenic mechanisms remain unclear. Proper mouse models of SS are essential for experiments. This article summarizes the recent advances in spontaneous mouse models of SS,genetically engineered mouse models of SS,and experimentally induced mouse models of SS.

[Clinical Observation of Chaihu Guizhi Decoction in Treating SAPHO Syndrome].

Objective To evaluate the clinical efficacy and safety of Modified Chaihu Guizhi De- coction on SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. Methods Totally 40 patients with SAPHO syndrome were randomized to the treatment group(20 cases) and control group(20 cases). The treatment group was treated with Modified Chaihu Guizhi Decoction, and the control group with alendronate sodium 70 mg each week. The therapeutic course for all was 12 weeks. The Visual Analogue Scale (VAS) pain scores, bath ankylosing spondylitis activity index (BASDAI) , bath ankylosing spondylitis functional index(BASFI) , erythrocyte sedimentation rate(ESR) and hypersensitivity C reactive protein (hs-CRP) were measured before and after treatment. Adverse events were observed. Results The VAS, BASDAI, and BASFI score significantly improved compared with baseline in the treatment group (P <0. 01 , P <0. 05). The VAS and BASDAI score of the treatment group improved compared with the control group after treatment (P <0. 05). Three patients in the control group reported adverse events with digestive tract symptoms, while there was no obvious adverse drug reactions in the treatment group. Conclusions Modified Chaihu Guizhi Decoction was superior to alendronate sodium in the treat- ment of SAPHO syndrome without obvious adverse drug reactions.

Health-related quality of life and psychological status of women with primary Sjögren's syndrome: A cross-sectional study of 304 Chinese patients.

Patients with primary Sjögren syndrome (pSS) always suffer from dryness, pain, and fatigue caused by the involvement of multiple different systems or organs. The uncomfortable disease symptoms, the consequent disability, and the side effects of therapeutic drugs decrease the quality of life and lead to emotional problems. We investigated the health-related quality of life and psychological status of a large cohort of women patients with pSS and associated factors.A total of 304 women with pSS referred to Peking Union Medical College Hospital during 2011 and 2014 were included. The internationally recognized Short Form (36) Health Survey (SF-36) was used to assess patients' quality of life; a higher score indicated a better quality of life. Patients' psychological status was assessed by the Hospital Anxiety and Depression Scale (HADS), and higher scores predicted more anxiety or depression.Patients with pSS had remarkably lower SF-36 scores. The Hospital Anxiety Scale (HAS) and Hospital Depression Scale (HDS) scores of the pSS patients (7 [4,10] and 6 [3,10], respectively) were significantly higher than that of patients with other internal diseases (3.37 ± 2.81 and 3.83 ±â€Š3.14; both P < .001). Negative predictors of quality of life were: pain (physical condition, ß = -0.225; P < .001); fatigue (physical condition, ß = -0.298; P < .001; and mental condition, ß = -0.319; P < .001). Risk factors for anxiety were: young age (ß = -0.059; P = .035); pain (ß = 0.025; P = .028); or fatigue (ß = 0.029; P = .004). Risk factors for depression were: xeroderma (ß = 0.030; P = .003); pain (ß = 0.022; P = .047); or fatigue (ß = 0.033; P = .001).Patients with pSS have a low quality of life with anxiety and depression. Pain and fatigue are primary factors for lower quality of life, which cause more anxiety and depression.

A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjögren's syndrome at 7q11.23.

Primary Sjögren's syndrome is one of the most common autoimmune diseases. So far, genetic studies of Sjögren's syndrome have relied mostly on candidate gene approaches. To identify new genetic susceptibility loci for primary Sjögren's syndrome, we performed a three-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 556,134 autosomal SNPs in 542 cases and 1,050 controls. We then validated promising associations in 2 replication stages comprising 1,303 cases and 2,727 controls. The combined analysis identified GTF2I at 7q11.23 (rs117026326: Pcombined = 1.31 × 10(-53), combined odds ratio (ORcombined) = 2.20) as a new susceptibility locus for primary Sjögren's syndrome. Our analysis also confirmed previously reported associations in Europeans in the regions of STAT4, TNFAIP3 and the major histocompatibility complex (MHC). Fine mapping of the region around GTF2I showed that rs117026326 in GTF2I had the most significant association, with associated SNPs extending from GTF2I to GTF2IRD1-GTF2I.