Icotinib has been widely used in patients with non-small cell lung cancer (NSCLC), and have significantly enhanced the overall survival rate of NSCLC patients. However, acquired drug resistance ...limits its clinical efficacy. Tumor cell-derived exosomes have been reported to participate in various biological processes, including tumor invasion, metastasis and drug resistance.
In the present study, drug resistance was measured by MTT assay. Exosomes were extracted from the cell supernatant using ultracentrifugation and identified by exosomal marker. HCC827 cells were treated with exosomes derived from icotinib-resistant (IR) HCC827 to observe the invasion and migration of parent cells. The expression of exo-mRNA was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-PCR). In addition, 10 exo-mRNAs detecting from the plasma and bronchoalveolar lavage fluid (BALF) of NSCLC patients with icotinib treatment were used to establish a new drug resistant-warning formula.
The oncogene MET into exosomes was identified from icotinib-resistant lung cancer cells, and this was also presented in exosomes in NSCLC patients diagnosed with cancer metastasis after icotinib treatment. The knockdown of MET in exosomes significantly decreased the ability of invasion and migration in HCC827 cells.
It was suggested that MET might be specifically package and transferred by exosomes to modify the invasion and migration ability of the surrounding icotinib-sensitive cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tobacco smoking is the main risk factor for many diseases such as chronic obstructive pulmonary disease as well as lung cancer and cigarettes. Smokers usually keep continuing to smoke during their ...mental activities in the evening between dinner and sleep time on work days. So it is critical to elucidate the relationship between cigarettes daily consumption and mental activities after dinner. A survey designed by ourselves was finished among 369 patients who came to our clinic for smoking cessation. Age, gender, BMI, cigarettes consumption were recorded and analyzed. Statistically, Pearson correlation test and general linear model test were used. Compared to ≤ 40 years' group, patients with mental activities after dinner consumed more cigarettes than those without mental activities (22.80 ± 10.86 vs. 30.88 ± 18.69, P value < 0.001). The Pearson correlation test showed no interact effects on age and BMI, and general linear model test showed that the cigarettes numbers between smokers with mental activities after dinner and smokers without mental activities after dinner are different (P value < 0.001). Mental activities from dinner finish to sleep time increase cigarettes consumption. It provides evidence that mental thinking activities after dinner is a risk factor of tobacco using.
There is growing evidence for the importance of 3' untranslated region (3'UTR) dependent regulatory processes. However, our current human 3'UTR catalogue is incomplete. Here, we develop a machine ...learning-based framework, leveraging both genomic and tissue-specific transcriptomic features to predict previously unannotated 3'UTRs. We identify unannotated 3'UTRs associated with 1,563 genes across 39 human tissues, with the greatest abundance found in the brain. These unannotated 3'UTRs are significantly enriched for RNA binding protein (RBP) motifs and exhibit high human lineage-specificity. We find that brain-specific unannotated 3'UTRs are enriched for the binding motifs of important neuronal RBPs such as TARDBP and RBFOX1, and their associated genes are involved in synaptic function. Our data is shared through an online resource F3UTER ( https://astx.shinyapps.io/F3UTER/ ). Overall, our data improves 3'UTR annotation and provides additional insights into the mRNA-RBP interactome in the human brain, with implications for our understanding of neurological and neurodevelopmental diseases.
Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease for which the genetic contribution is incompletely understood.
We conducted a joint analysis of 5,523,934 imputed SNPs in two ...newly-genotyped progressive supranuclear palsy cohorts, primarily derived from two clinical trials (Allon davunetide and NNIPPS riluzole trials in PSP) and a previously published genome-wide association study (GWAS), in total comprising 1646 cases and 10,662 controls of European ancestry.
We identified 5 associated loci at a genome-wide significance threshold P < 5 × 10
, including replication of 3 loci from previous studies and 2 novel loci at 6p21.1 and 12p12.1 (near RUNX2 and SLCO1A2, respectively). At the 17q21.31 locus, stepwise regression analysis confirmed the presence of multiple independent loci (localized near MAPT and KANSL1). An additional 4 loci were highly suggestive of association (P < 1 × 10
). We analyzed the genetic correlation with multiple neurodegenerative diseases, and found that PSP had shared polygenic heritability with Parkinson's disease and amyotrophic lateral sclerosis.
In total, we identified 6 additional significant or suggestive SNP associations with PSP, and discovered genetic overlap with other neurodegenerative diseases. These findings clarify the pathogenesis and genetic architecture of PSP.
Gene set enrichment analysis (detecting phenotypic terms that emerge as significant in a set of genes) plays an important role in bioinformatics focused on diseases of genetic basis. To facilitate ...phenotype-oriented gene set analysis, we developed PhenoExam, a freely available R package for tool developers and a web interface for users, which performs: (1) phenotype and disease enrichment analysis on a gene set; (2) measures statistically significant phenotype similarities between gene sets and (3) detects significant differential phenotypes or disease terms across different databases.
PhenoExam generates sensitive and accurate phenotype enrichment analyses. It is also effective in segregating gene sets or Mendelian diseases with very similar phenotypes. We tested the tool with two similar diseases (Parkinson and dystonia), to show phenotype-level similarities but also potentially interesting differences. Moreover, we used PhenoExam to validate computationally predicted new genes potentially associated with epilepsy.
We developed PhenoExam, a freely available R package and Web application, which performs phenotype enrichment and disease enrichment analysis on gene set G, measures statistically significant phenotype similarities between pairs of gene sets G and G' and detects statistically significant exclusive phenotypes or disease terms, across different databases. We proved with simulations and real cases that it is useful to distinguish between gene sets or diseases with very similar phenotypes. Github R package URL is https://github.com/alexcis95/PhenoExam . Shiny App URL is https://alejandrocisterna.shinyapps.io/phenoexamweb/ .
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Antiphospholipid syndrome (APS) is an autoimmune disease mainly characterised by vascular thrombosis and pregnancy morbidity. APS has broad spectrum of clinical manifestations. The digestive system ...involvement of antiphospholipid syndrome is a critical but under-recognised condition. Digestive system involvement may be the result of direct (autoimmune-mediated) or indirect (thrombotic) mechanisms. Liver is the most commonly involved organ, followed by intestines, oesophagus, stomach, pancreas and spleen. This review describes possible digestive system manifestations in APS patients, and illustrates the epidemiology and possible pathophysiology of APS. The role of different treatment strategies in the management of digestive system manifestations of APS were also discussed.
Key messages
Antiphospholipid syndrome is a multi-organ, multi-system disease and its clinical manifestation spectrum is gradually expanding. Since the first diagnosis of APS, the clinical manifestations of digestive system have been reported successively. This narrative review describes the major digestive system manifestations of APS and illustrates the epidemiology, pathophysiology and the role of therapeutic strategies of these patients.
INTRODUCTIONCigarette and tobacco use is a leading cause of chronic obstructive pulmonary disease, lung cancer, and other malignant tumors. In China, people prefer to engage in mental activities ...(gambling, overtime work, playing video games, or other mental activities) on the weekends or during spare time, especially in the evening before they prepare for bed. In China, smokers frequently consume tea while smoking. The relationship between smokers who consume tea, engage in mental activities after dinner, or both (drinking tea and engaging in cognitive activities after dinner together), and daily cigarette smoking or nicotine addiction must be clarified. METHODSA total of 438 smokers were included in the study. Age, gender, body mass index (BMI), smoking habits, Fagerström test for nicotine dependence scores, and behaviors, were recorded. The study excluded smokers with a Fagerström score <1 or with a mental disorder diagnosis. The smokers were divided into four groups based on their behaviors: those who did not drink tea, did not engage in mental activities after dinner, those who drank tea only, those who engaged in mental activities only, and those who engaged in both. RESULTSOnly drinking tea or doing mental activities after dinner cannot increase cigarettes per day (22.20 ± 10.143 vs 23.49 ± 11.966, p=0.362; 22.20 ± 10.143 vs 22.66 ± 1.192, p=0.750) or FTND scores 6.0 (4.0; 7.0) vs 6.0 (4.0; 7.75), p=0.941; 6.0 (4.0; 7.0) vs 6.0 (4.25; 7.75), p=0.980. People who drink tea and engage in mental activities after dinner smoke more (22.20 ± 10.143 vs 30.75 ± 17.264, p<0.0001) and have higher nicotine dependence levels 6.0 (4.0; 7.0) vs 7.0 (5.0; 8.0), p=0.015. CONCLUSIONSThe consumption of tea or a mental activity after dinner is not associated with daily smoking or nicotine dependence. There is an association between the combined behaviors (tea drinking and mental activity after dinner) and the daily consumption of cigarettes, and the degree of nicotine dependence.
Introduction: Nicotine dependence (ND) is a maladaptive pattern of tobacco smoking with withdrawal symptoms similar to other drug addictive disorders. It is very common in clinical practice that ...smokers always have different degrees of nicotine dependence with the same amount of tobacco consumption. Behaviors may influence daily cigarette consumption or smoking status. Hence it is critical to ascertain the association between concurrent behaviors and high nicotine dependence among smokers. Methods: A total of 343 patients who attended a clinic for smoking cessation were recruited, and the information on concurrent behaviors were recorded. Factors associated and not associated with nicotine dependence were recorded. Nicotine dependence was determined by Fagerström test for nicotine dependence (FTND). Results: High ND patients (FTND > 5) showed significant behaviors distribution compared with mild and moderate ND patients (FTND ≤ 5). There is no single behavior that was significantly different between high ND and mild and moderate ND smokers. However, the combined effects of nicotine dependence influencing behaviors of caffeine drinking and mental activities after dinner have an association with high ND (OR=1.939; 95% CI: 1.154 – 3.258, p=0.012). In addition, the combined effects of inadequate sleep time (< 8 hours), caffeine drinking and mental activities after dinner significantly distinguished patients of high ND from those of low ND (OR=2.208; 95% CI: 1.032 – 4.737, p=0.042). Conclusions: Interaction effects of mental activities after dinner and caffeine drinking have an association with high nicotine dependence. Sleep of less than 8 hours with behaviors of mental activities after dinner and caffeine drinking have the same effect.
In recent years, various biomarkers have been gradually applied on bronchoalveolar lavage (BAL) fluid for the diagnosis of invasive pulmonary aspergillosis (IPA). The objective of this study is to ...assess the value of the liquid-based cytopathology test (LCT) for improving the identification of IPA in BAL fluid from possible IPA patients, following special staining with periodic acid-Schiff staining (PAS) or Grocott’s methenamine silver (GMS). A total of 47 consecutive possible IPA patients who underwent bronchoscopy with BAL fluid from January 2017 to December 2018 were included. 45 people had a pair of BAL fluid specimens and 2 patients had two BAL fluid specimens. The 49 pairs of BAL fluid specimens were processed for culture, tuberculosis acid fast staining smear, direct microbial smear, and LCT with special staining (PAS and GMS), respectively. Then, we compared the sensitivity and specificity of PAS and GMS in BAL fluid in high-risk patients. Among 47 possible IPA patients, 25 patients had proven/probable IPA, and 11 patients had other invasive fungal diseases. The sensitivity of GMS was higher than that of PAS (92.11% versus 81.58%; P=0.175). The specificity of GMS was 81.82%, which was higher than that of PAS (81.82% versus 72.73%; P=0.611). The negative predictive value (NPV) for PAS and GMS were 53.33% and 75.00%, respectively. The positive predictive value (PPV) for PAS and GMS were 91.18% and 94.59%, respectively. This study showed that special staining of LCT in BAL fluid may be a novel method for the diagnosis of IPA, and the GMS of LCT had higher sensitivity and specificity, which was superior to PAS.
Patients with anti-CV2/collapsin response mediator protein (CRMP)5 antibodies present with more frequent chorea, cerebellar ataxia, uveo/retinal symptoms, and Lambert–Eaton myasthenic syndrome or ...myasthenia gravis. Chronic intestinal pseudo-obstruction (CIPO) is an intestinal motility dysfunction disease dysmotility that is caused by a neuromuscular disease with recurrent or persistent intestinal obstruction in the absence of mechanical obstruction. We report the case of a patient with CRMP5 antibody-positive paraneoplastic neurological syndrome (PNS) that is associated with autonomic dysfunction (presenting most remarkably as CIPO). CIPO is one of the rarest forms of PNS. Some PNS patients who are positive for anti-CV2/CRMP5 antibodies may have fatal complications such as CIPO. To detect if PNS patients are at risk for CIPO, a timely diagnosis and appropriate treatment are required.
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