SummaryIncreasing evidence indicates that aberrant neutrophil extracellular trap (NET) formation could contribute to the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Recent research has provided evidence that a novel type of ANCA autoantibody, anti-lysosomal membrane protein-2 (LAMP-2) antibody, may have a pathogenic role in AAV. We have shown previously that anti-LAMP-2 antibody-stimulated NET formation contains autoantigens and antimicrobial peptides. The current study sought to determine whether LAMP-2, as a novel antigen of ANCA, was present on NETs in AAV patients, the influence of the anti-LAMP-2 antibody on the neutrophil apoptosis rate and the role of autophagy in anti-LAMP-2 antibodyinduced NET formation. NET formation was assessed using immunofluorescence microscopy, scanning electron microscopy or live cell imaging. The neutrophil apoptosis rate was analysed using fluorescence activated cell sorting (FACS). Autophagy was detected using LC3B accumulation and transmission electron microscopy. The results showed that enhanced NET formation, which contains LAMP-2, was observed in kidney biopsies and neutrophils from AAV patients. The apoptosis rate decreased significantly in human neutrophils stimulated with anti-LAMP-2 antibody, and this effect was attenuated by the inhibitors of autophagy 3-methyladenine (3MA) and 2-morpholin-4-yl-8-phenylchromen-4-one (LY294002). The anti-LAMP-2 antibody-stimulated NET formation was unaffected by benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethylketone (zVAD-fmk) and necrostatin-1 (Nec-1), which are inhibitors of apoptosis and necrosis, respectively, but was inhibited by 3MA and LY294002. Moreover, the proportion of LC3BI that was converted to LC3BII increased significantly (P 5 0Á0057), and massive vacuolizations that exhibited characteristics typical of autophagy were detected in neutrophils stimulated with anti-LAMP-2 antibody. Our results provide further evidence that autophagy is involved in ANCAinduced NET formation in human neutrophils.

Obesity, a chronic, low-grade inflammatory disease, is associated with alterations of multiple immune-cell components in the visceral adipose tissue (VAT), in which CD4(+) Foxp3(+) regulatory T cells (Tregs) have been suggested to be a critical regulator. This review focuses on the current understanding of VAT-resident Tregs (VAT Tregs) and their intriguing roles in modulating fat tissue inflammation and obesity-associated metabolic disorders. The potential mechanisms for the regulation of VAT Tregs in lean vs. obese individuals are also discussed. Accumulating evidence reveals that the modulation of VAT Tregs may offer a potential novel strategy for treating obesity-related metabolic disorders, such as insulin resistance and type 2 diabetes.

The current study develops a two-factor (communication and emotional distance) IAP, which offers a reliable tool to assess experienced alienation of affection toward parents in children aged between 8 and 19 years old. Our result is the first investigation of experienced alienation and potential influential factors in Chinese left-behind children. The findings that children with absent mother experience higher alienation toward parents, as well as three recognized risk factors for alienation of affection toward parents (poor communication with absent parents, worse left-behind condition, and psychosocial vulnerability), give valuable guidance for parents who intend to leave or who are already leaving as well as for government policymaking.

Background: Pancreatic duct adenocarcinoma (PDAC) remains a devastating disease with little improvement in survival figures over the last decades. Better characterization and identification of high risk groups are needed to tailor their management. Herein we explore the prognostic role of different clinical biomarkers in patients with PDAC treated with FOLFIRINOX.Methods: We retrospectively audited patients with locally advanced inoperable or metastatic PDAC that received FOLFIRINOX as first-line treatment in West Yorkshire, UK, between 09/2010 and 09/2019. Different prognostic clinical biomarkers were evaluated in multivariate models. Results:The study included 138 pts with advanced pancreatic adenocarcinoma. 87 (63%) were males and 51 (37%) females. Median age was 62 years (range, 29-77). 66 (47.8%) had excellent performance status (PS ECOG 0), 71 (51.4%) PS 1 and one pt (0.8%) had PS ECOG 2. Charlson comorbidity index (CCI) was 0 in 66 (47.8%) of pts, 1 in 25 (18.1%), 2 in 16 (11.6%) and !3 in 31 (22.5%) pts. 78 (56.5%) had metastatic and 60 (43.5%) locally advanced disease. Median blood hemoglobin levels were 128 g/L (range, 81-171), median white blood cell (WBC) levels 8.17/uL (3.42-33.50), neutrophil (NEUT) levels 5.68/nL (range, 1.98-22.13), lymphocyte (LYMPH) 1.58/nL (range, 0.31-4.90), monocyte (MONO) 0.51/nL (range, 0.16-1.86), platelet (PLT) 271/nL (range, 90-631) and median serum albumin (ALB) levels 39 g/L (range, 24-51). Median neutrophilto-lymphocyte ratio (NLR) was 3.58 (range, 1.13-25.29), monocyte-to-lymphocyte ratio (MLR) 0.36 (range, 0.10-1.10), platelet-to-lymphocyte ratio (PLR) 176.46 (range, 42.40-678-48), prognostic nutritional index (PNI¼ALB+[5ÂLYMPH]) was 47.08 (range, 28.95-66.55) and systemic inflammation response index (SIRI¼NEUT Â MONO/LYMPH) was 1.89 (range, 0.31-21.75). After a median follow-up of 42.7 months (range, 0.3-64.9), 128 (92.8%) patients died. Median overall survival (OS) was 9.