CD44 is associated with muscle inflammation in polymyositis and skin damage in idiopathic inflammatory myopathy.

OBJECTIVES: Idiopathic inflammatory myopathy (IIM) is a group of systemic autoimmune diseases characterised by muscle involvement. This study aims to reveal the characteristics of IIM subtypes and explore the molecular mechanisms underlying IIM. METHODS: The STRING database was utilised to construct a protein-protein interaction network of differentially expressed genes obtained from the GSE128470, GSE3112, and GSE39454 datasets. The immune cell infiltration level was assessed by CIBERSORT in polymyositis (PM). Experimental autoimmune myositis (EAM) model mice were constructed for experimental verification. Serum levels of soluble CD44 (sCD44) were measured using enzyme-linked immunosorbent assay. RESULTS: The upregulated hub gene CD44 was highly expressed in inflammatory cells infiltrating the skeletal muscle of patients with PM and in EAM mice. CD44 was correlated with both M1 macrophages (r=0.57, p<0.0001) and M2 macrophages (r=0.57, p<0.0001) in PM. Additionally, CD44+F4/80+ macrophages in skeletal muscle were increased (p<0.0001) and CD44 showed a stronger association with markers of M1 macrophage in EAM mice. Moreover, serum sCD44 levels were elevated in patients with IIM (p=0.0024), PM (p=0.0332) and dermatomyositis (p=0.0001) notably in the anti-melanoma differentiation-associated gene 5 antibody positive subtype (p=0.0007). sCD44 levels also positively correlated with visual analogue score (r=0.4424, p=0.0013), myositis intention to treat activity index (r=0.3938, p=0.0047), skin damage score (r=0.3796, p=0.0101) and skin activity score (r=0.4625, p=0.0014) in patients with IIM. CONCLUSIONS: This study suggests that macrophages expressing CD44 may be involved in the pathogenesis of PM, and sCD44 could serve as a potential marker for skin damage and activity in IIM.

Influence of Anesthetic Techniques on Perioperative Outcomes after Endovascular Aneurysm Repair.

BACKGROUND: The purpose of the study was to explore the influence of anesthetic techniques on perioperative outcomes after endovascular aneurysm repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA) in a Chinese population. METHODS: A retrospective review was performed in patients after elective EVAR for infrarenal AAA at our single center. Patients were classified into general anesthesia (GA), regional anesthesia (RA), and local anesthesia (LA) groups. The primary outcomes (30-day mortality and morbidity) and secondary outcomes [procedure time, mean arterial pressure (MAP), and length of hospital stay (LOS)] were collected and analyzed. RESULTS: From January 2006 to December 2015, 486 consecutive patients underwent elective EVAR at our center. GA was used in 155 patients (31.9%), RA in 56 (11.5%), and LA in 275 (56.6%). The GA patients had fewer respiratory comorbidities, shorter and more angulated proximal necks, and more concomitant iliac aneurysms. LA during EVAR was significantly associated with a shorter procedure time (GA, P < 0.001; RA, P < 0.001) and shorter LOS (GA, P = 0.002; RA, P = 0.001), but a higher MAP (GA, P < 0.001; RA, P < 0.001) compared with GA and RA. LA was associated with a significantly lower risk of cardiac (odds ratio (OR) 4.27, 95% confidence interval (CI) 1.21-15.04), pulmonary (OR 5.37, 95% CI 1.58-18.23), and systemic complications (OR 4.15, 95% CI 1.85-9.33) compared with GA. RA was also associated with a decreased risk of systemic complications (OR 4.74, 95% CI 1.19-18.92) compared with GA. There was no difference in the 30-day mortality, neurologic complications, renal complications, and intraoperative extra procedures among the 3 groups. CONCLUSIONS: Anesthetic techniques for EVAR have no influence on the 30-day mortality. LA for EVAR appears to be beneficial concerning the procedure time, LOS, and 30-day systemic complications for patients after elective EVAR for infrarenal AAA in the Chinese population.

Systematic Review and Meta-analysis of Current Literature on Isolated Abdominal Aortic Dissection.

OBJECTIVE: To present the pooled quantitative evidence of basic profiles, initial treatment strategies, and clinical outcomes in patients with isolated abdominal aortic dissection (IAAD). METHODS: A comprehensive systematic review and meta-analysis was performed of all available studies reporting IAAD, retrieved from the MEDLINE, Embase, and Cochrane Databases. The logistic normal random effect model was fitted using the generalised linear mixed model with random intercepts to calculate the pooled proportion estimates. RESULTS: Seventeen studies with 482 patients were included in this meta-analysis. Male smokers with hyperlipidaemia and hypertension were the most prominent basic profile. IAADs were predominantly spontaneous and infrarenal, and roughly half were acute and symptomatic. Approximately 67% [95% confidence interval (CI) 42-86%] of patients were managed initially conservatively. In the overall population, the 30 day all cause mortality was 3% (95% CI 1-5%) and the long term mortality during follow up was 8% (95% CI 5-14%). Re-intervention during follow up occurred in 8% (95% CI 5-15%) of patients. In the subgroup analysis, patients with conservative treatment had a 30 day mortality of 1% (95% CI 0-8%), a long term mortality of 5% (95% CI 1-29%), and a re-intervention rate of 18% (95% CI 10-29%). Patients with open surgery had a 30 day mortality of 9% (95% CI 0-82%), a long term mortality of 12% (95% CI 4-31%), and a re-intervention rate of 9% (95% CI 1-44%). Patients with endovascular repair had a 30 day mortality of 2% (95% CI 0-10%), a long term mortality of 5% (95% CI 2-13%), a re-intervention rate of 6% (95% CI 3-13%), and a persistent endoleak rate of 4% (95% CI 2-10%). CONCLUSION: Appropriate initial treatment strategies can be used to obtain acceptable clinical outcomes in patients with IAAD. Invasive intervention is necessary if patients match certain indications for intervention. Regular imaging surveillance should be provided for all patients, especially those treated conservatively.

What Factors Contribute to Reading in ADHD: Examining Reading-Related Skills in Children With ADHD Only/Comorbid Developmental Dyslexia.

BACKGROUND: ADHD and developmental dyslexia (DD) frequently co-occur. However, it is unclear why some children with ADHD acquire DD while others do not. METHODS: A total of 830 children (including typically developing controls, ADHD only, DD only, and ADHD + DD groups) of two ages (younger: first-third grade; older: fourth-sixth grade) were assessed on measures of reading ability and reading-related skills. RESULTS: The clinical groups had different degrees of impairment in each reading-related skill. Regression results found that the four groups had different skills in predicting reading ability in younger and older grades. Especially, rapid automatized naming (RAN) was the only predictor of reading ability in children with ADHD only. CONCLUSIONS: The study highlights that RAN plays an important role in the reading development of children with ADHD only, reflecting the possible protective role of RAN in reading development.

Adenosine A2B receptor activation regulates the balance between T helper 17 cells and regulatory T cells, and inhibits regulatory T cells exhaustion in experimental autoimmune myositis.

BACKGROUND: Idiopathic inflammatory myopathy (IIM) is a systemic autoimmune disease characterized by skeletal muscle involvement. This study aimed to investigate the role of adenosine receptor signalling pathways in the development of experimental autoimmune myositis (EAM). METHODS: An ecto-5'-nucleotidase (CD73) inhibitor, adenosine receptor agonists, a hypoxia-inducible factor-1α (HIF-1α) inhibitor or a vehicle were administered to control and EAM mice. Murine splenic CD4+ or regulatory T cells (Tregs) were isolated using magnetic beads and subsequently stimulated with an adenosine A2B receptor agonist, a HIF-1α inhibitor, or vehicle in vitro. In cross-sectional studies, we collected 64 serum samples (69% female, 49 ± 9 years), 63 peripheral blood samples (70% female, 50 ± 11 years), and 34 skeletal muscle samples (71% female, 63 ± 6 years) from patients with IIM. Additionally, 35 serum samples and 30 peripheral blood samples were obtained from age- and sex-matched healthy controls, and six quadriceps muscle samples were collected from patients with osteoarthritis to serve as the normal group. RESULTS: Patients with IIM exhibited increased CD73 [dermatomyositis (DM), polymyositis (PM): P < 0.01; immune-mediated necrotizing myopathy (IMNM): P < 0.0001] and adenosine deaminase (ADA) expression (DM: P < 0.001; PM, IMNM: P < 0.0001) in the skeletal muscles, and serum ADA levels [56.7 (95% CI: 53.7, 58.7) vs. 198.8 (95% CI: 186.2, 237.3) ng/µL, P < 0.0001]. Intervention with a CD73 inhibitor exacerbated (P = 0.0461), whereas adenosine receptor agonists (A1: P = 0.0009; A2B: P < 0.0001; A3: P = 0.0001) and the HIF-1α inhibitor (P = 0.0044) alleviated skeletal muscle injury in EAM mice. Elevated expression of programmed cell death protein-1 (PD1: P = 0.0023) and T-cell immunoglobulin and mucin-domain containing-3 (TIM3: P < 0.0001) in skeletal muscles of patients with IIM were correlated with creatine kinase levels (PD1, r = 0.7072, P < 0.0001; TIM3, r = 0.4808, P = 0.0046). PD1+CD4+ (r = 0.3243, P = 0.0115) and PD1+CD8+ (r = 0.3959, P = 0.0017) T cells were correlated with Myositis Disease Activity Assessment Visual Analogue Scale scores (muscle) in IIM. The exhausted Tregs were identified in the skeletal muscles of patients with IIM. Activation of the A2B adenosine receptor downregulated HIF-1α (protein or mRNA level, P < 0.01), resulting in decreased T helper cell 17 (Th17) (13.58% vs. 5.43%, P = 0.0201) and phosphorylated-signal transducer and activator of transcription 3 (p-STAT3)+ Th17 (16.32% vs. 6.73%, P = 0.0029), decreased exhausted Tregs (PD1+ Tregs: 53.55% vs. 40.28%, P = 0.0005; TIM3+ Tregs: 3.93% vs. 3.11%, P = 0.0029), and increased Tregs (0.45% vs. 2.89%, P = 0.0006) in EAM mice. CONCLUSIONS: The exhausted T cells may be pathogenic in IIM, and the activation of adenosine A2B receptor signalling pathway can regulate Th17/Treg balance and inhibit Tregs exhaustion, thereby slowing EAM disease progression.

Systematic review and meta-analysis of the current literature on tocilizumab in patients with refractory Takayasu arteritis.

Objective: To present the pooled quantitative evidence of baseline characteristics and clinical outcomes of tocilizumab (TCZ) in patients with refractory Takayasu arteritis (TAK). Methods: A comprehensive systematic review and meta-analysis was performed on all available studies retrieved from the MEDLINE, Embase, and Cochrane databases, using TCZ in patients with refractory TAK. We applied the commands metan and metaprop_one in Stata Software to pool overall estimates of continuous data and binomial data, respectively. A random-effects model was recruited for analysis. Results: Nineteen studies with 466 patients were included in this meta-analysis. The mean age at implementation of TCZ was 34.32 years. Female sex and Numano Type V were the most prominent baseline characteristics. During the 12-month follow-up when receiving TCZ treatment, pooled CRP was 1.17 mg/L (95% confidence interval [CI] -0.18-2.52), pooled ESR was 3.54 mm/h (95% CI 0.51-6.58), and pooled glucocorticoid dose was 6.26 mg/d (95% CI 4.24-8.27). Approximately 76% (95% CI 58-87%) of patients achieved a decrease in glucocorticoid dosage. Meanwhile, patients with TAK had a remission rate of 79% (95% CI 69-86%), a relapse rate of 17% (95% CI 5-45%), an imaging progress rate of 16% (95% CI 9-27%), and a retention rate of 68% (95% CI 50-82%). Adverse events occurred in 16% (95% CI 5-39%) of patients, and infection was the most common adverse event, with a rate of 12% (95% CI 5-28%). Conclusion: TCZ treatment can provide favorable outcomes in terms of inflammatory markers, steroid-sparing effects, clinical response, drug retention and minimizing adverse effects for patients with refractory TAK.

Stretch Formability of an AZ61 Alloy Plate Prepared by Multi-Pass Friction Stir Processing.

The stretch formability behavior of an AZ61 magnesium alloy plate produced by multi-pass friction stir processing (M-FSP) was investigated, with the applied load vs. displacement curves recorded during Erichsen cupping tests at different punching speeds at room temperature. The stretch formability of M-FSP AZ61 magnesium alloy was significantly enhanced, compared with that of its cast counterpart. The highest Erichsen index of 3.7 mm was obtained at a punching speed of 0.1 mm/min. The improved stretch formability was mainly attributed to the grain refinement stemming from the M-FSP and the presence of extension twinning to accommodate deformation during Erichsen cupping testing.

[Separation strategy of affinity chromatography for mixed antibodies].

A mammary gland bioreactor can efficiently express human recombinant monoclonal antibody. However, the target products are similar to the bovine antibody in the raw emulsion material in properties and structures. Thus it is difficult to achieve effective separation of the target products. In this work, the species differences between bovine antibody and recombinant human antibody were analyzed and a new separation strategy was raised based on it. We employed two kinds of affinity chromatography to separate these two antibodies from each other and studied the effect of elution mode upon separation. The results demonstrated that Protein A affinity chromatography could get hybrid antibodies using gradient elution mode, but hardly separate the recombinant human antibody and bovine antibody from each other. In contrast, the combination of Protein A affinity chromatography and displacement chromatography could separate the hybrid antibodies effectively and finally give recombinant human IgG (rHGG) product with the purity of 95% and the yield of more than 95%. Immuno-affinity chromatography could also effectively purify recombinant monoclonal antibodies and owned better generality, which could be used in purification of recombinant antibody expressed by any animal mammary gland. -

[Separation of coagulation factor VIII with high activity using gigaporous anion exchange chromatography].

A purification process to obtain coagulation factor VIII (F VIII) with high activity from human plasma was established. Based on the analysis of the size ratio between F VIII and matrix porous medium and its effect on the protein activity, a novel purification process designed was superporous ion exchange chromatography (IEC). The operating conditions of gigaporous and traditional anion exchange chromatography were optimized separately. The chromogenic substrate, gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were used to monitor the bioactivity and purity of the chromatographic products. The results showed that the superporous medium could not only protect structure of macro-protein but also enhance its mass transfer, finally giving FVIII product with high activity. The yield of F VIII in superporous chromatography was about five times of commercially agarose chromatography and the specific activity was up to 154 IU/mg protein. Furthermore, we studied the regeneration process of the superporous medium, washing the column with 5 column volumes of 1 mol/L NaOH at a low flow rate, to ensure the chromatographic stability. This purification process is simple, reproducible and suitable for large-scale production.