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Tumor microenvironment (TME) plays a core role in the genesis and progress of endometrial carcinoma (EC). The immune system, a crucial element of TME, functions in various immune cells. In this paper, we have tried to evaluate the prognosis in EC patients by the status of TME. The ESTIMATE algorithm was implemented to computer the number of immune and stromal components in EC tissues from the Cancer Genome Atlas dataset. The CIBERSORT algorithm was employed to assess the proportion of tumor-infiltrating immune cells in EC tissues, which were quantified as Stromal score and Immune score. After the construction of protein-protein interaction network, cell-cell chemokine receptor 2 (CCR2) was identified as a potential predictive element for EC. Further analysis indicated that a higher expression of CCR2 in EC patients was correlated with a better prognosis and a prolonged disease-free survival. According to the transcript level of CCR2, samples were separated into low- and high-expression groups. Gene Set Enrichment Analysis unveiled that metabolism-related pathways were mostly abundant in groups with high-expression, the other one was primarily correlated to immune-related activities. We figured out that some immune cells were positively related to CCR2, suggesting that CCR2 might serve as the immune-dominant status of TME, which was verified by qRT-PCR and HPA analysis in transcriptome and protein level, respectively. Also, CCR2 showed high correlation with immune modulators and chemokine signaling pathway. Thus, the level of CCR2 might have a prognostic value for EC patients, which provides a novel insight for therapeutic strategies of EC.The present study explored the cooperative effect of both alanine (Ala) and gentamicin (Gent) on metabolic mechanisms by which exogenous Ala potentiates Gent to kill antibiotic-resistant Vibrio alginolyticus. To test this, GC-MS-based metabolomics was used to characterize Ala-, Gent- and both-induced metabolic profiles, identifying nitric oxide (NO) production pathway as the most key clue to understand metabolic mechanisms. Gent, Ala and both led to low, lower and lowest activity of total nitric oxide synthase (tNOS) and level of NO, respectively. NOS promoter L-arginine and inhibitor NG-Monomethyl-L-arginine inhibited and promoted the killing, respectively, with the elevation and decrease of NOS activity and NO level. The present study further showed that CysJ is the enzyme-producing NO in V. alginolyticus. Wnt inhibitor These results indicate that the cooperative effect of Ala and Gent causes the lowest NO, which plays a key role in Ala-potentiated Gent-mediated killing.
Genetic factors have been studied to be associated with diabetic retinopathy (DR). This study aimed to investigate the association between the polymorphisms in the
(
) gene and DR in a Han Chinese population.
There were 475 patients with diabetic retinopathy (DR), 478 type 2 diabetes mellitus without retinopathy (DNR) and 469 healthy controls collected in this study.
single-nucleotide polymorphisms (SNPs) rs2073618 and rs3134069 were genotyped by Mass ARRAY MALDI-TOF system. The genotype and allele frequencies were evaluated using the χ
tests. Odds ratio (OR) and 95% confidence intervals (95% CI) were calculated for the risk of genotype and allele.
There was a statistically significant difference for
SNP rs3134069 between DR cases and healthy controls in the allelic model (
= .036, OR= 1.33, 95% CI=1.02-1.73). The C allele frequency of this polymorphism was 0.154 in the DR cases, whereas it was 0.120 in healthy controls, suggesting a risk effect for DR. SNP rs3134069 had a significant association with DR in the dominant model (
= .038, OR= 1.37, 95% CI=1.02-1.84), indicating that the CC/AC genotype was more likely to suffer from DR. For rs2073618, no significant difference was identified in the allelic model (
= .632, OR= 0.95, 95% CI=0.78-1.16) and the four genetic models.
This study showed that
SNP rs3134069 was associated with DR in the dominant model, suggesting that the
gene variant may be involved in the development of DR.
This study showed that OPG SNP rs3134069 was associated with DR in the dominant model, suggesting that the OPG gene variant may be involved in the development of DR.Background Inflammation and oxidative stress contribute to the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury (ALI). MicroRNA-762 (miR-762) has been implicated in the progression of inflammation and oxidative stress; however, its role in ALI remains unclear. In this study, we aim to investigate the role and underlying mechanisms of miR-762 in LPS-induced ALI. Methods Mice were intravenously injected with miR-762 antagomir, agomir or the negative controls for 3 consecutive days and then received a single intratracheal instillation of LPS (5 mg/kg) for 12 h to establish ALI model. Adenoviral vectors were used to knock down the endogenous SIRT7 expression. Results An increased miR-762 expression was detected in LPS-treated lungs. miR-762 antagomir significantly reduced inflammation, oxidative stress and ALI in mice, while the mice with miR-762 agomir treatment exhibited a deleterious phenotype. Besides, we found that SIRT7 upregulation was essential for the pulmonoprotective effects of miR-762 antagomir, and that SIRT7 silence completely abolished the anti-inflammatory and anti-oxidant capacities of miR-762 antagomir. Conclusion miR-762 is implicated in the pathogenesis of LPS-induced ALI via modulating inflammation and oxidative stress, which depends on its regulation of SIRT7 expression. It might be a valuable therapeutic target for the treatment of ALI.Background Interfacility transfers (IFTs) are an essential component of healthcare systems to allow movement of patients between facilities. It is essential to limit any delays in patients receiving the care they require at the receiving facility. The primary objective of this study was to assess whether IFT response time was reduced after implementation of an AutoLaunch protocol, in which an ambulance is dispatched to the sending facility prior to acceptance of the patient by the receiving facility. The secondary objective was to describe the frequency and amount of time ambulances had to stage outside the sending facility in situations where the ambulance arrived prior to the patient being accepted by the receiving facility. Methods This was a retrospective pre-post analysis of patients undergoing IFT for services not available at the sending facility between October 1, 2018 and September 30, 2019, with the AutoLaunch protocol being implemented on March 25, 2019. IFT response time was defined as the time the transfer request was initially made to the time the ambulance arrived at the sending facility.
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