Background To investigate the recent epidemiological trends of gastric neuroendocrine neoplasms (GNENs) and establish a new tool to estimate the prognosis of gastric neuroendocrine carcinoma (GNEC) and gastric neuroendocrine tumor (GNET). Methods Nomograms were established based on a retrospective study on patients diagnosed with GNENs from 1975 to 2016 in Surveillance, Epidemiology and End Results database. External validation was performed among 246 GNENs patients in Jiangsu province to verify the discrimination and calibration of the nomograms. Results The age-adjusted incidence of GNENs has increased from 0.309 to 6.149 per 1,000,000 persons in the past 4 decades. Multivariate analysis indicated independent prognostic factors for both GNEC and GNET including age, distant metastasis and surgical intervention (P < 0.05). In addition, T, N staging and grade were significantly associated with survival of GNEC, while size was a predictor for GNET (P < 0.05). The C-indexes of the nomograms were 0.840 for GNEC and 0.718 for GNET, which were higher than those of the 8th AJCC staging system (0.773 and 0.599). Excellent discrimination was observed in the validation cohorts (C-index of nomogram vs AJCC staging for GNEC: 0.743 vs 0.714; GNET: 0.945 vs 0.927). Survival rates predicted by nomograms were close to the actual survival rates in the calibration plots in both training and validation sets. Conclusions The incidence of the GNENs is increasing steadily in the past 40 years. We established more excellent nomograms to predict the prognosis of GNENs than traditional staging system, helping clinicians to make tailored decisions.
Stab wounds are the main type of penetrating cardiac injury in China and they have a fairly good prognosis when the patient receives expeditious and appropriate management. The objective of this study is to present the experience of managing the patients with penetrating cardiac injuries. A retrospective study involving 82 cases with penetrating wounds of the heart in the past 16 years was carried out. Stab wounds accounted for 86.58% of this series (71 of 82 patients). All 82 cases were treated operatively. The amount of preoperative infusion as fluid resuscitation for shock was less than 1,000 ml in 65.85% of the present study. Only in three patients was preoperative pericardiocentesis performed, yielding a false-negative result in one. Six patients sustaining cardiac arrest soon after arrival were subjected to emergency room thoracotomy (ERT), and five of them survived. The overall survival rate was 96.34%. One patient died of exsanguination due to injury of multiple chambers; of the remaining 2 deaths after operation 1 was associated with abdominal injuries and the other with failure of cerebral resuscitation. From the experience reported in this study, early establishment of diagnosis and prompt thoracotomy against time are the fundamental factors affecting the outcome of penetrating cardiac injuries. Preoperative massive transfusion and pericardiocentesis are not advocated.
Polymorphisms of IL-1beta/-1470, IL-1beta/-511, IL-1beta/-31, IL-4/-589, IL-6/-572, IL-8/-251, IL-10/-819, and TNFalpha/-308 are susceptibility loci for the development of sepsis and organ dysfunction in major trauma patients.
IntroductionAn excessive inflammatory response is thought to account for the pathogenesis of sepsis and multiple organ dysfunction syndrome (MODS) after severe trauma. The interleukin-10 (IL-10) is a potent anti-inflammatory cytokine. The objectives of this prospective study were to investigate the distribution of IL-10 promoter polymorphisms in a cohort of 308 Chinese Han patients with major trauma, and to identify associations of IL-10 promoter polymorphisms with IL-10 production and incidence of sepsis and MODS.MethodsA total of 308 patients with major trauma were included in this study. The genotypes of polymorphisms -1082, -819 and -592 were determined by polymerase chain reaction-restriction fragment length polymorphism. The IL-10 levels in the supernatants were determined with enzyme-linked immunoabsorbent assay.ResultsThe -1082A and -592A alleles were significantly associated with lower lipopolysaccharide-induced IL-10 production in an allele-dose dependent fashion. There was no significant difference for the -819 polymorphism. Except for the -1082 polymorphism, the -819 and -592 polymorphisms were not significantly associated with sepsis morbidity rate and MOD scores.ConclusionsOur results further confirm the functionality of the IL-10 promoter single nucleotide polymorphisms in relation to IL-10 production. They also suggest that individual difference in IL-10 production in trauma patients might be at least in part related to genetic variations in the IL-10 promoter region.
E-cadherin expressed highly in 95C and lowly in 95D lung cancer cells which were from the same patient, but core-fucosylated E-cadherin highly expressed in 95D cells. Therefore, Fut8 and Fut8-RNAi constructs were transfected into 95C and 95D cells, respectively. In Fut8-transfectants, reduction of nuclear beta-catenin was noted when E-cadherin was core-fucosylated, while accumulation of nuclear beta-catenin was observed in Fut8-RNAi transfectants. In E-cadherin-negative MDA-MB-231 cells either Fut8 or Fut8-RNAi transfection couldn't affect nuclear beta-catenin. However, cotransfection of E-cadherin with Fut8 caused nuclear beta-catenin reduction. Furthermore, enhanced binding of E-cadheirn with beta-catenin as well as alpha-catenin were observed in Fut8-transfectants, and reduction of tyrosine 654 phosphorylation on beta-catenin and its transcriptional activity were also noted at the same time. Overall, the current results suggested that core-fucosylated E-cadherin regulated nuclear beta-catenin accumulation in lung cancer cells.
Highlights d TBP is modified by the nutrient sensor O-GlcNAc d T114-O-GlcNAc-TBP regulates B-TFIID complex formation d Dysregulation of T114-O-GlcNAc-TBP results in large changes in the transcriptome d Lack of T114-O-GlcNAc-TBP results in cellular lipid droplets accumulation
IntroductionThe nucleotide-binding oligomerization domain-like receptor (NLR) family has been recognized as comprising intracellular pattern recognition receptors in which NLRP3 (NLR family, pyrin domain containing 3) plays an important role in the initiation of host immune inflammatory responses. The genetic variants have been recognized to be critical determinants of interindividual differences in both inflammatory responses and clinical outcomes in critical illness. However, little is known about the clinical relevance of NLRP3 gene polymorphisms in critical illness.MethodsA total of 718 patients with major blunt trauma were included in this study. Six tag SNPs (tSNPs) were selected from the entire NLRP3 gene through construction of haplotype bins, and they were genotyped using a pyrosequencing method. They were analyzed in relation to sepsis morbidity rate, multiple organ dysfunction (MOD) scores and IL-1β production. Moreover, the functionality of the rs2027432 polymorphism was assessed by the observation of its effect on transcriptional activities.ResultsAmong the six tSNPs genotyped in this study, two of them (rs2027432 and rs12048215) were significantly associated with sepsis morbidity rate and MOD scores. A significant association was also observed between these two polymorphisms and IL-1β production by peripheral leukocytes in response to ex vivo lipopolysaccharide stimulation. However, no combined effects were found between these two polymorphisms. In addition, the rs2027432 polymorphism could significantly enhance the promoter activities of the NLRP3 gene.Conclusionsrs2027432 and rs12048215 polymorphisms might be used as relevant risk estimates for the development of sepsis and MOD syndrome in patients with major trauma, in which rs2027432 might be a functional SNP.
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