Many people in Beijing perceive that most members of their society have negative beliefs towards people with mental illness. Further efforts are needed to determine if these perceptions are accurate and to reduce the stigma that is reinforced by these perceptions.

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Cyclooxygenase-2 (COX-2) is overexpressed in various types of human malignancies including esophageal squamous cell carcinoma (ESCC). However, a subset of ESCC either do not express COX-2 or show low level of expression. It is well established that promoter methylation is a major mechanism that mediates transcriptional silencing of COX-2 in gastric and colorectal cancer, but the data on ESCC are very limited. In this study, we attempted to determine whether COX-2 expression was also regulated by promoter methylation in human ESCC cell lines. We examined the methylation status of the COX-2 promoter in five human ESCC cell lines (EC109, EC9706, KYSE 410, KYSE 150, TE-1) using bisulfite sequencing analysis. Western blot analysis was used to determine COX-2 expression. Quantitative real-time polymerase chain reaction was used to determine COX-2 mRNA level. Prostaglandin (PG) E(2) was detected by ELISA. The promoter was densely methylated in TE-1 and KYSE 150, which had a low level of COX-2 expression and less methylated in other three cell lines (EC109, EC9706, KYSE 410), with high level of COX-2 expression. Treatment with 5-aza-deoxycytidine (5-aza-DC), a DNA methyltransferase inhibitor, demethylated the promoter and upregulated COX-2 expression, as well as PGE(2) production in TE-1 and KYSE 150. However, no such effects were observed in EC109. COX-2 protein was negative, but mRNA was positive in TE-1. After treatment with 5-aza-DC, both COX-2 mRNA and protein level had increased. These findings suggest that the promoter methylation may be one of the mechanisms that regulate COX-2 expression in ESCC.

Preexisting DM predicts worse patient and graft survivals of LT. Concomitant HCV infection would further deteriorate this unfavorable impact. Given the high heterogeneities and the insufficient evidences, more studies are still warranted to support these observations.

Introduction As the pharmacokinetics (PK) of factor VIII (FVIII) is individualized in children with haemophilia A (HA), PK parameters may be indicators of patients' bleeding phenotype and instruction for their personalized replacement program. Aim The aim of this study was to investigate the possible relationship between PK/FVIII level and bleeding frequency in Chinese paediatric patients with severe (HA). Methods A total of 24 patients were enrolled in Beijing Children's Hospital from February to October 2015, all of whom were given 50 IU/kg of FVIII concentrates after a 72‐hours washout period. Samples' activities (FVIII:C) were tested at 5 time points, using WinNonlin software for PK testing, and then the individual half‐life(t1/2) and the time (h) of FVIII concentrations <1 IU/dL within a week during prophylaxis were calculated. Baseline and the annual bleeding rate (ABR), annual joint bleeding rate (AJBR) were recorded and analyzed. Results The mean t1/2 of FVIII was 10.20 ± 2.72 hours and the mean time of FVIII <1 IU/dL in 1 week was 44.7 hours (−38.56 to 102.33 hours). A significant relationship between t1/2 of FVIII and ABR0/AJBR0 (baseline bleeding) was found (R2 = 0.75 and 0.62, P < .001). Besides, baseline and the annual bleeding rate during prophylactic treatment of haemophilia had a positive correlation with the time (hours) of FVIII <1 IU/dL in 1 week (R2 = 0.67 and 0.52, P < .001). Conclusion t1/2 was an important indicator to prevent bleeding in severe HA; the frequency of bleeding will be reduced with the increased of t1/2 of FVIII. The data also demonstrates that increasing the time with a FVIII<1 IU/dL is associated with an increased rate of bleeding during prophylaxis.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely challenging disease with a high mortality rate and a short overall survival time. The poor prognosis can be explained by aggressive tumor growth, late diagnosis, and therapy resistance. Consistent efforts have been made focusing on early tumor detection and novel drug development. Various strategies aim at increasing target specificity or local enrichment of chemotherapeutics as well as imaging agents in tumor tissue. Aptamers have the potential to provide early detection and permit anti-cancer therapy with significantly reduced side effects. These molecules are in-vitro selected single-stranded oligonucleotides that form stable threedimensional structures. They are capable of binding to a variety of molecular targets with high affinity and specificity. Several properties such as high binding affinity, the in vitro chemical process of selection, a variety of chemical modifications of molecular platforms for diverse function, non-immunoreactivity, modification of bioavailability, and manipulation of pharmacokinetics make aptamers attractive targets compared to conventional cell-specific ligands. To explore the potential of aptamers for early diagnosis and targeted therapy of PDAC-as single agents and in combination with radiotherapy-we summarize the generation process of aptamers and their application as biosensors, biomarker detection tools, targeted imaging tracers, and drug-delivery carriers. We are furthermore discussing the current implementation aptamers in clinical trials, their limitations and possible future utilization.

The maintenance of psoriasis as a skin-confined chronic inflammatory condition requires the abnormal interplay between hyperproliferative epidermal keratinocytes and self-reactive immune cells. In this context, targeting metabolism of keratinocytes is recently reported to be an approach for treating psoriasis, however whether and how the metabolic adaptations of keratinocytes introduce inflammatory cues are unknown. We report that in psoriatic lesions, Protein Phosphatase 6 (PP6) is diminished in the epidermis, and its levels negatively correlate with the disease severity. Mice with genetic deficiency of Pp6 in keratinocytes spontaneously develop psoriasis-like skin phenotype resembling psoriasis clinically, histologically, in its gene expression profile and in its response to therapy. Mechanistically, Pp6-/keratinocytes rely on inordinate urea cycle along with enhanced oxidative phosphorylation (OXPHOS) to hyper-proliferate, mediated by increased Arginase-1 (Arg1) production resulting from the activation of CCAAT/enhancer-binding protein beta (C/EBPb). Single-cell RNA-seq reveals the Arginine biosynthesis rate-limiting enzyme, Argininosuccinate synthetase 1 (ASS1), maintains the pool of Arginine in psoriatic epidermis. Moreover, accumulated polyamines branched from urea cycle promote self-RNA sensing by myeloid dendritic cells with the assistance of an RNA-binding peptide originated from heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), a probable autoantigen in psoriasis, which directly links keratinocyte hyperproliferation to autoimmune responses. Targeting metabolic nodes of urea cycle in imiquimod-induced mouse and non-human primate models of psoriasis markedly improves the skin inflammation. Thus, our data reveal for the first time the molecular basis of an auto-inflammatory condition and the functional significance of target organ-intrinsic metabolic reprogramming in inflammation, bringing forth novel insights into the pathogenesis and therapeutic strategies of chronic inflammatory disorders.

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