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.
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.
Abnormal angiogenesis and dysfunction of macrophage polarization in diabetic skin ulcers leads to non-healing wound. Huiyang Shengji Extract (HSE)is a traditional Chinese medicine prescribed for the treatment of chronic wounds. This study aims to investigate the effect and molecular mechanism of HSE on wound healing of diabetic mice. Diabetic db/db mice were operated with full-thickness excision, with wound treated externally by HSE. The results showed that HSE reduces the wound area on days 7 and 14; Compared with the model group on day 10, the local blood flow of the wound of HSE group was significantly increased according to Doppler ultrasound imaging. More neovascularization was seen in the wounds of HSE group through histological observation on day 14; VEGFR2 mRNA and protein levels could be increased on day 14. It is suggested that HSE promotes angiogenesis during granulation tissue formation. Compared with the model group, HSE increased the expression of CD68 and CD206 (M2 marker) in the wounds, decreased the expression of iNOS(M1 marker) on day 3, decreased the mRNA level of IL-6, IL-12A and TNF-a(M1 marker) in the wound on day 7 (P<0.01). It is suggested that HSE promote M1 macrophages polarize to M2 cells in wounds. In conclusion, HSE promoted angiogenesis and regulated the macrophage polarization to transit the wound from inflammatory phase to proliferative phase, a potential therapeutic mechanism of HSE for the chronic diabetic wound.
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