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Background: The atherogenic index of plasma (AIP) and hyperuricemia (HUA) have been shown to be closely associated with morbidity and mortality of coronary artery disease. However, studies targeting predictive value of AIP and HUA for chronic total occlusion (CTO) lesions are still lacking. Methods: In total, 5,238 patients meeting the eligibility criteria were recruited in this analysis. CTO was defined as the condition of lesions without forward blood flow and with over three months of occlusion time. AIP was calculated as log10 [triglycerides (mmol/L)/high-density lipoprotein cholesterol (mmol/L)]. HUA was defined based on sex-specific criteria: serum uric acid 420 and 360â µmol/L for males and females, respectively. Results: CTO lesions were presented in 907 (17.3%) patients. Compared with patients showing lower AIP levels and non-HUA, the CTO lesion risks increased by 5.225 and 2.765 times in patients with higher AIP levels and HUA. Patients with AIP >0.15 and HUA exhibited the greatest CTO incidence (odds ratio 11.491; 95% confidence interval 9.019-14.641, P < 0.001). In addition, AIP combined with HUA had significantly increased effects (a 38.5% increase in CTO risk) relative to the sum of respective effects. Conclusion: Patients having higher AIP levels and HUA exhibited the highest CTO incidence, in comparison with patients who have the increased single index. AIP combined with HUA displayed significant synergistic effect on the prediction of CTO lesion.
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Cancer cells frequently upregulate ribosome production to support tumorigenesis. While small nucleolar RNAs (snoRNAs) are critical for ribosome biogenesis, the roles of other classes of noncoding RNAs in this process remain largely unknown. Here we performed CRISPRi screens to identify essential long noncoding RNAs (lncRNAs) in renal cell carcinoma (RCC) cells. This revealed that an alternatively-spliced isoform of lncRNA Colorectal Neoplasia Differentially Expressed containing an ultraconserved element (UCE), referred to as CRNDE UCE, is required for RCC cell proliferation. CRNDE UCE localizes to the nucleolus and promotes 60S ribosomal subunit biogenesis. The UCE of CRNDE functions as an unprocessed C/D box snoRNA that directly interacts with ribosomal RNA precursors. This facilitates delivery of eIF6, a key 60S biogenesis factor, which binds to CRNDE UCE through a sequence element adjacent to the UCE. These findings highlight the functional versatility of snoRNA sequences and expand the known mechanisms through which noncoding RNAs orchestrate ribosome biogenesis.
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The effect of systemic inflammation, represented by high-sensitivity C-reactive protein (hsCRP), on triglyceride glucose (TyG) index-associated cardiovascular risk in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has not yet been determined. This study was a retrospective analysis of a single-center prospective registry and finally included 1701 patients (age, 60 ± 10 years; male, 76.7%). The primary endpoint was defined as major adverse cardiovascular events (MACE), including cardiovascular mortality, non-fatal stroke, and non-fatal myocardial infarction. In the multivariate COX regression model that included the GRACE risk score, higher TyG index was significantly associated with a greater incidence of MACE in patients with hsCRP levels less than 2 mg/L but not 2 mg/L or more (P for interaction = 0.039). Each unit increase in the TyG index was independently associated with a 52% increased risk of MACE only in patients with hsCRP levels less than 2 mg/L (P = 0.021). After adjustment for other confounding factors, including the GRACE risk score, compared with those in the group of TyG index < 8.62 and hsCRP < 2 mg/L, patients in the group of TyG index ≥ 8.62 and hsCRP ≥ 2 mg/L had a 3.9 times higher hazard ratio for developing MACE. The addition of both TyG index and hsCRP had an incremental effect on the predictive ability of the GRACE risk score-based prognostic model for MACE (C-statistic: increased from 0.631 to 0.661; cNRI: 0.146, P = 0.012; IDI: 0.009, P < 0.001). In conclusion, there was a significant interaction between the TyG index and hsCRP for the risk of MACE, and the TyG index was reliably and independently associated with MACE only when hsCRP levels were less than 2 mg/L. Furthermore, high TyG index and high hsCRP levels synergistically increased the risk of MACE, suggesting that the prognostic value of TyG index combined with hsCRP might be promising in patients with ACS undergoing PCI.
Subject(s)
Acute Coronary Syndrome , C-Reactive Protein , Percutaneous Coronary Intervention , Triglycerides , Humans , Male , Acute Coronary Syndrome/blood , Middle Aged , C-Reactive Protein/metabolism , C-Reactive Protein/analysis , Percutaneous Coronary Intervention/adverse effects , Female , Aged , Triglycerides/blood , Retrospective Studies , Risk Factors , Blood Glucose/analysis , Blood Glucose/metabolism , Biomarkers/bloodABSTRACT
Cellular senescence is an irreversible state of cell-cycle arrest induced by various stresses, including aberrant oncogene activation, telomere shortening, and DNA damage. Through a genome-wide screen, we discovered a conserved small nucleolar RNA (snoRNA), SNORA13, that is required for multiple forms of senescence in human cells and mice. Although SNORA13 guides the pseudouridylation of a conserved nucleotide in the ribosomal decoding center, loss of this snoRNA minimally impacts translation. Instead, we found that SNORA13 negatively regulates ribosome biogenesis. Senescence-inducing stress perturbs ribosome biogenesis, resulting in the accumulation of free ribosomal proteins (RPs) that trigger p53 activation. SNORA13 interacts directly with RPL23, decreasing its incorporation into maturing 60S subunits and, consequently, increasing the pool of free RPs, thereby promoting p53-mediated senescence. Thus, SNORA13 regulates ribosome biogenesis and the p53 pathway through a non-canonical mechanism distinct from its role in guiding RNA modification. These findings expand our understanding of snoRNA functions and their roles in cellular signaling.
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BACKGROUND: Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding transcription factor in eukaryotes, regulates the proliferation of cancer cells by activating downstream target genes and then participates in the formation and progression of tumors, including lung cancer (LC). The expression level of MTF1 is down-regulated in LC, and high expression of MTF1 is associated with a good prognosis of LC. However, the association between MTF1 polymorphism and LC risk has not been explored. METHODS: The genotyping of MTF1 Single nucleotide polymorphisms (SNPs) including rs473279, rs28411034, rs28411352, and rs3748682 was identified by the Agena MassARRAY system among 670 healthy controls and 670 patients with LC. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistics regression to assess the association of these SNPs with LC risk. RESULTS: MTF1 rs28411034 (OR 1.22, 95% CI 1.03-1.45, p = 0.024) and rs3748682 (OR 1.24, 95% CI 1.04-1.47, p = 0.014) were associated with higher LC susceptibility overall. Moreover, the effect of rs28411034 and rs3748682 on LC susceptibility was observed in males, subjects with body mass index (BMI) ≥ 24 kg/m2, smokers, drinkers, and patients with lung squamous carcinoma (OR and 95% CI > 1, p < 0.05). Besides, rs28411352 (OR 0.73, 95% CI 0.55-0.97, p = 0.028,) showed protective effect for reduced LC risk in drinkers. CONCLUSIONS: We were first who reported that rs28411034 and rs3748682 tended to be relevant to increased LC susceptibility among the Chinese Han population. These results of this study could help to recognize the pathogenic mechanisms of the MTF1 gene in LC progress.
Subject(s)
Asian People , DNA-Binding Proteins , Genetic Predisposition to Disease , Lung Neoplasms , Polymorphism, Single Nucleotide , Transcription Factor MTF-1 , Transcription Factors , Humans , Lung Neoplasms/genetics , Male , Female , Middle Aged , Transcription Factors/genetics , Asian People/genetics , DNA-Binding Proteins/genetics , Case-Control Studies , China/epidemiology , Aged , Genotype , Risk Factors , East Asian PeopleABSTRACT
Excessive soil salinity is a major stressor inhibiting crops' growth, development, and yield. Seed germination is a critical stage of crop growth and development, as well as one of the most salt-sensitive stages. Salt stress has a significant inhibitory effect on seed germination. Okra is a nutritious vegetable, but its seed germination percentage (GP) is low, whether under salt stress conditions or suitable conditions. In this study, we used 180 okra accessions and conducted a genome-wide association study (GWAS) on the germination percentage using 20,133,859 single nucleotide polymorphic (SNP) markers under 0 (CK, diluted water), 70 (treatment 1, T1), and 140 mmol/L (treatment 2, T2) NaCl conditions. Using the mixed linear model (MLM) in Efficient Mixed-model Association eXpedated (EMMAX) and Genome-wide Efficient Mixed Model Association (GEMMA) software, 511 SNP loci were significantly associated during germination, of which 167 SNP loci were detected simultaneously by both programs. Among the 167 SNPs, SNP2619493 on chromosome 59 and SNP2692266 on chromosome 44 were detected simultaneously under the CK, T1, and T2 conditions, and were key SNP loci regulating the GP of okra seeds. Linkage disequilibrium block analysis revealed that nsSNP2626294 (C/T) in Ae59G004900 was near SNP2619493, and the amino acid changes caused by nsSNP2626294 led to an increase in the phenotypic values in some okra accessions. There was an nsSNP2688406 (A/G) in Ae44G005470 near SNP2692266, and the amino acid change caused by nsSNP2688406 led to a decrease in phenotypic values in some okra accessions. These results indicate that Ae59G004900 and Ae44G005470 regulate the GP of okra seeds under salt and no-salt stresses. The gene expression analysis further demonstrated these results. The SNP markers and genes that were identified in this study will provide reference for further research on the GP of okra, as well as new genetic markers and candidate genes for cultivating new okra varieties with high GPs under salt and no-salt stress conditions.
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BACKGROUND: Acute Myeloid Leukemia (AML) generally has a relatively low survival rate after treatment. There is an urgent need to find new biomarkers that may improve the survival prognosis of patients. Machine-learning tools are more and more widely used in the screening of biomarkers. METHODS: Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine-Recursive Feature Elimination (SVM-RFE), Random Forest (RF), eXtreme Gradient Boosting (XGBoost), lrFuncs, IdaProfile, caretFuncs, and nbFuncs models were used to screen key genes closely associated with AML. Then, based on the Cancer Genome Atlas (TCGA), pan-cancer analysis was performed to determine the correlation between important genes and AML or other cancers. Finally, the diagnostic value of important genes for AML was verified in different data sets. RESULTS: The survival analysis results of the training set showed 26 genes with survival differences. After the intersection of the results of each machine learning method, DNM1, MEIS1, and SUSD3 were selected as key genes for subsequent analysis. The results of the pan-cancer analysis showed that MEIS1 and DNM1 were significantly highly expressed in AML; MEIS1 and SUSD3 are potential risk factors for the prognosis of AML, and DNM1 is a potential protective factor. Three key genes were significantly associated with AML immune subtypes and multiple immune checkpoints in AML. The results of the verification analysis show that DNM1, MEIS1, and SUSD3 have potential diagnostic value for AML. CONCLUSION: Multiple machine learning methods identified DNM1, MEIS1, and SUSD3 can be regarded as prognostic biomarkers for AML.
Subject(s)
Leukemia, Myeloid, Acute , Humans , Prognosis , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , Machine Learning , Risk Factors , Support Vector MachineABSTRACT
BACKGROUND: Acute lung injury (ALI) is an acute inflammatory respiratory disease. The interaction between growth arrest-specific 6 (Gas6) and tyrosine kinases of the Tyro3, Axl, Mer (TAM) family plays an important role in a variety of physiological and pathological processes, including inflammation. In this study, we mainly clarified the mechanism of the Gas6/TAM signal pathway in lipopolysaccharide (LPS)-induced pulmonary epithelial cells (BEAS-2B cells) injury. METHODS: We cultured BEAS-2B cells in vitro and established a LPS-induced BEAS-2B cells injury model. Then, the siRNA sequence (siGas6-2) was transfected into cells. The expression of Gas6/TAM was measured based on quantitative reverse transcription polymerase chain reaction (qRT-RCR) and western blot (WB). Cell proliferation and apoptosis were measured by cell counting Kit-8 (CCK-8) and flow cytometry. The expression of pro-inflammatory factors was measured by qRT-RCR and WB. RESULTS: Our study showed that when the 40 µg/mL LPS-induced BEAS-2B cells injury model was established, cell viability was significantly reduced, but the Gas6/TAM signal pathway was activated. When transfection with siGas6-2, low expression of Gas6 directly reduced the expression of downstream TAM receptors. Furthermore, the inhibition of the Gas6/TAM signal pathway significantly reduced the occurrence of cell apoptosis and the expression of inflammatory factors, and promoted cell proliferation. CONCLUSION: Our research indicated that Gas6/TAM played an important role in cell proliferation, apoptosis, and inflammatory response in the LPS-induced BEAS-2B cells injury, and Gas6/TAM may be a new target in the treatment of ALI in the future.
Subject(s)
Acute Lung Injury , Lipopolysaccharides , Receptor Protein-Tyrosine Kinases , Signal Transduction , Humans , Acute Lung Injury/chemically induced , Axl Receptor Tyrosine Kinase , Epithelial Cells/metabolism , Intercellular Signaling Peptides and Proteins/genetics , Lipopolysaccharides/pharmacology , Proto-Oncogene Proteins/metabolism , Receptor Protein-Tyrosine Kinases/genetics , Receptor Protein-Tyrosine Kinases/metabolismABSTRACT
Background: Lung cancer is one of the most common human malignant diseases. In this study, we aimed to explore the association between IL1RL1 genetic polymorphisms and lung cancer risk in the Chinese Han population. Methods: We selected and genotyped six SNPs in the IL1RL1 gene using the Agena MassARRAY system in 507 lung cancer patients and 507 healthy controls. The association between IL1RL1 variants and lung cancer risk was assessed using logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Multi-factor dimensionality reduction (MDR) was used to analyze the impact of SNP-SNP interactions on the risk of lung cancer. Results: The results of overall analysis indicated that rs12479210 (T vs. C: OR = 1.42, FDR-p = 0.002; TC vs. CC: OR = 1.70, FDR-p < 0.0001; TT vs. CC: OR = 1.77, FDR-p = 0.032; TT-TC vs. CC: OR = 1.71, FDR-p = 0.001; additive: OR = 1.44, FDR-p = 0.001) and rs1420101 (T vs. C: OR = 1.31, FDR-p = 0.036; TT-TC vs. CC: OR = 1.42, FDR-p = 0.031; additive: OR = 1.30, FDR-p = 0.030) were associated with an increased the risk of lung cancer among the Chinese Han population. Stratified analysis also found the association between these two SNPs and lung cancer risk. However, there were no significant association observed between the other four SNPs (rs3771180, rs3771175, rs10208293, and rs10197862) in IL1RL1 and lung cancer risk. Furthermore, MDR analysis showed that rs12479210 was the best single model with the highest testing accuracy (0.566) and perfect CVC (10/10) for predicting lung cancer risk. The expression level of the IL1RL1 gene is lower in lung cancer tissue than normal tissue, and there are significant differences in the expression levels of IL1RL1 between rs12479210 and rs1420101 genetypes in lung cancer tissue (p < 0.05). Conclusion: Our findings suggest that IL1RL1 genetic variants (rs12479210 and rs1420101) are associated with an increased lung cancer risk in the Chinese Han population. These risk variants may serve as biomarkers for the prevention and treatment of lung cancer.
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Phosphodiesterase 4D interacting protein (PDE4DIP) interacts with cAMP-specific phosphodiesterase 4D and its abnormal expression promotes the development of hematological malignancies, breast cancer, and pineal cell carcinoma. However, there is currently no systematic pan-cancer analysis of the association between PDE4DIP and various cancers. Thus, this study aimed to elucidate the potential functions of PDE4DIP in various cancers. Based on the multiple public databases and online websites, we conducted comprehensive analyses for PDE4DIP in various cancers, including differential expression, prognosis, genetic variation, DNA methylation, and immunity. We thoroughly analyzed the specific role of PDE4DIP in acute myeloid leukemia (LAML). The results indicated that there were differences in PDE4DIP expression in cancers, and in kidney chromophobe, LAML, pheochromocytoma and paraganglioma, thymoma, and uveal melanoma, PDE4DIP had potential prognostic value. PDE4DIP expression was also correlated with genetic variation, DNA methylation, immune cell infiltration, and immune-related genes in cancers. Functional enrichment analysis showed that PDE4DIP was mainly related to immune-related pathways in cancers, and in LAML, PDE4DIP was mainly related to immunoglobulin complexes, T-cell receptor complexes, and immune response regulatory signaling pathways. Our study systematically revealed for the first time the potential prognostic and immunotherapeutic value of PDE4DIP in various cancers, including LAML.
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Both cis- and trans- tetracyclic spiroindolines are the core of many important biologically active indole alkaloids, but the divergent synthesis of these important motifs is largely hampered by the limited stereoselectivity control. A facile stereoinversion protocol is reported here in Michael addition-initiated tandem Mannich cyclizations for constructing tetracyclic spiroindolines, providing an easy access to two diastereoisomeric cores of monoterpene indole alkaloids with high selectivity. The mechanistic studies including in situ NMR experiments, control experiments, and DFT calculations reveal that the reaction undergoes a unique retro-Mannich/re-Mannich rearrangement including a C-C bond cleavage that is very rare for a saturated six-membered carbocycle. Insights into the stereoinversion process have been uncovered, and the major effects were determined to be the electronic properties of N-protecting groups of the indole with the aid of Lewis acid catalysts. By understanding these insights, the stereoselectivity switching strategy is also smoothly applied from enamine substrates to vinyl ether substrates, which are enriched greatly for the divergent synthesis and stereocontrol of monoterpene indole alkaloids. The current reaction also proves to be very practical and was successfully applied to the gram-scale total synthesis of strychnine and deethylibophyllidine in short routes.
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Introduction: This study aimed to investigate the effects of smoking and CYP2C19 gene polymorphism on antiplatelet therapy to specify the most optimized and accurate antiplatelet therapy for different populations. Methods: This study included 6,353 patients with coronary artery disease (CAD). In total, 2,256 (35.5%) were smokers and 4,097 (64.5%) were non-smokers. Patients carrying a CYP2C19*2 or *3 allele were considered loss-of-function (LOF) allele carriers. The medical history of patients who had undergone percutaneous coronary intervention (PCI) at Beijing Anzhen Hospital was recorded. The primary endpoint was major adverse cardiovascular or cerebrovascular events (MACCE) during the 6-month follow-up period. A Cox regression model was used to assess the interactions between antiplatelet efficacy and CYP2C19 LOF allele carrier status, stratified by smoking status. Results: Compared to clopidogrel plus aspirin, ticagrelor plus aspirin reduced the MACCE recurrence risk in non-smokers (carrier: 6.0 vs. 2.0%, hazard ratio 0.298, 95% confidence interval 0.204-0.635, P < 0.0001; non-carrier: 5.8 vs. 2.1%, hazard ratio 0.358, 95% confidence interval 0.189-0.678, P = 0.002), and not in smokers. Similar results were discovered regarding the recurrence rate for hospitalization for ischemic cardiac events in non-smokers. No apparent difference was discovered in the bleeding events in either group. There were no significant associations between antiplatelet medication and CYP2C19 LOF allele carrier status for the MACCE recurrence risk among smokers (P = 0.943, respectively) or non-smokers (P = 0.774, respectively). Conclusion: In patients with CAD after PCI, ticagrelor plus aspirin lowered the MACCE recurrence risk in CYP2C19 LOF allele carriers and non-carriers compared with clopidogrel plus aspirin alone among non-smokers. The efficacy of antiplatelet therapy varies between CYP2C19 LOF allele carrier status. No significant interaction between CYP2C19 LOF allele carrier status and antiplatelet effectiveness was observed. However, caution should be used to interpret our results considering the many limitations of our investigation.
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Background: Peripheral artery disease (PAD) elevates the risk of adverse outcomes. The current work aimed to evaluate the influence of PAD in acute coronary syndrome (ACS) cases administered percutaneous coronary intervention (PCI), and to determine whether PAD adds incremental prognostic value to the global registry of acute coronary events (GRACE) scale. Methods: To retrospectively analyze a single-center, prospective cohort trial, we consecutively included ACS cases administered PCI. Individuals with and without PAD were comparatively examined for clinical outcomes. The primary endpoint was major adverse cardiovascular events (MACEs), a compound item encompassing all-cause death, myocardial infarction (MI), stroke and repeat revascularization. The added value of PAD based on a reference model was examined. Results: PAD was detected in 179 (10.4%) of the 1,770 included patients. The incidence rates of MACEs (40.3% vs. 17.9%), all-cause death (11.2% vs. 1.6%), cardiovascular death (8.9% vs. 1.4%), MI (8.4% vs. 2.2%) and repeat revascularization (30.2% vs. 15.2%) were all markedly elevated in PAD cases in comparison with the non-PAD group (p < 0.001). After adjusting for other confounding variates, PAD independently predicted MACE occurrence (hazard ratio = 1.735, 95% confidence interval: 1.281-2.351). Addition of PAD resulted in remarkably increased predictive performance for MACE compared to the baseline GRACE score (Harrell's C-statistic: 0.610 vs. 0.587, p < 0.001; net reclassification improvement: 0.134, p < 0.001; integrated discrimination improvement: 0.035, p < 0.001). Conclusions: In ACS cases administered PCI, PAD independently worsens clinical outcomes and adds incremental value to the GRACE risk score.
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Background: Estimated glucose disposal rate (eGDR) is highly associated with all-cause mortality in type 2 diabetes mellitus (T2DM) cases undergoing coronary artery bypass grafting (CABG). Nevertheless, eGDR's prognostic value in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) following percutaneous coronary intervention (PCI) remains unknown. Methods: The population of this retrospective cohort study comprised NSTE-ACS patients administered PCI in Beijing Anzhen Hospital between January and December 2015. The primary endpoint was major adverse cardiac and cerebral events (MACCEs). eGDR was calculated based on waist circumference (WC) ( eGDR WC ) or body mass index (BMI) ( eGDR BMI ). Results: Totally 2308 participants were included, and the mean follow-up time was 41.06 months. The incidence of MACCEs was markedly increased with decreasing eGDR. Multivariable analysis showed hazard ratios (HRs) for eGDR WC and eGDR BMI of 1.152 (95% confidence interval [CI] 1.088-1.219; p < 0.001) and 0.998 (95% CI 0.936-1.064; p = 0.957), respectively. Addition of eGDR WC to a model that included currently recognized cardiovascular risk factors markedly enhanced its predictive power compared with the baseline model (Harrell's C-index, eGDR WC versus Baseline model, 0.778 versus 0.768, p = 0.003; continuous net reclassification improvement (continuous-NRI) of 0.125, p < 0.001; integrated discrimination improvement (IDI) of 0.016, p < 0.001). Conclusions: Low eGDR independently predicts low survival of NSTE-ACS cases who underwent PCI.
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BACKGROUND: Lung cancer is the leading cause of cancer death globally. Recent studies have revealed that CYP19A1 gene plays a crucial role in cancer initiation and development. The aim of this study was to assess the association of CYP19A1 genetic polymorphisms with the risk of lung cancer in the Chinese Han population. METHODS: This study randomly recruited 489 lung cancer patients and 467 healthy controls. The genotypes of four single nucleotide polymorphisms (SNPs) of the CYP19A1 gene were identified by the Agena MassARRY technique. Genetic model analysis was used to assess the association between genetic variations and lung cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the effect of four selected SNPs on lung cancer risk. RESULTS: CYP19A1 rs28757157 might contribute to an increased risk of lung cancer (p = 0.025, OR = 1.30, 95% CI 1.03-1.64). In stratified analysis, rs28757157 was associated with an increased cancer risk in the population aged under 60 years, females, smokers, and drinkers. Besides, rs3751592 and rs59429575 were also identified as risk biomarkers in the population under 60 years and drinkers. Meanwhile, a relationship between an enhanced risk of squamous cell carcinoma and rs28757157 was found, while the rs3751592 CC genotype was identified as a risk factor for lung adenocarcinoma development. CONCLUSIONS: This study has identified revealed that the three SNPs (rs28757157, rs3751592, and rs59429575) of CYP19A1 are associated with lung cancer in the Chinese Han population. These findings will provide theoretical support for further functional studies of CYP19A1 in lung cancer.
Subject(s)
Genetic Predisposition to Disease , Lung Neoplasms , Female , Humans , Aged , East Asian People , Case-Control Studies , Polymorphism, Single Nucleotide , Lung Neoplasms/epidemiology , Lung Neoplasms/genetics , Genotype , Risk Factors , China/epidemiology , Aromatase/geneticsABSTRACT
BACKGROUND: Cytochrome P450 (CYP) enzymes are involved in the metabolism of xenobiotic and carcinogen. In the study, we evaluated the association of CYP2J2 and CYP2C9 variants with lung cancer. METHOD: Five polymorphisms in CYP2J2 and four polymorphisms in CYP2C9 were genotyped in 507 lung cancer patients and 505 controls with Agena MassARRAY platform. The linkage of variants with lung cancer risk was evaluated by odds ratio (OR) and 95% confidence interval (CI) in genetic models and haplotype analyses. RESULTS: We found that CYP2C9 rs1934967 alleles were associated with lung cancer risk (P < 0.05). In stratified analysis, rs2280274 (women, non-smoker, non-drinker and lymphatic metastasis), rs11207535 (non-smoker and non-drinker), rs10889159 (non-smoker and non-drinker) of CYP2J2, whereas rs1934967 (age ≤ 60m, BMI > 24, squamous carcinoma) of CYP2C9 decreased lung cancer risk (P < 0.05). In addition, the results of linkage disequilibrium (LD) analysis showed that rs2280274|rs4388726 - TG (with adjustment: P = 0.042) of CYP2J2 and rs10509679|rs1934967|rs1934968|rs9332220 - GTGG (without adjustment: P = 0.044) of CYP2C9 were linked with a significantly decreased lung cancer risk. CONCLUSION: Our results indicated genetic variants in CYP2J2 and CYP2C9 might contribute to the susceptibility of lung cancer in Chinese population.
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Background: Triglyceride-glucose (TyG) index, a novel surrogate marker of insulin resistance, has been demonstrated to be significantly associated with cardiovascular disease. It remains indistinct regarding the association between TyG index and non-culprit coronary plaque characteristics in patients following acute coronary syndrome (ACS). Methods: The present study retrospectively recruited patients who were diagnosed with ACS and underwent non-culprit optical coherence tomography (OCT) examination. The study population was divided into 2 groups based on the median of TyG index, which was calculated as Ln [fasting triglyceride (TG) (mg/dL) × fasting blood glucose (FBG) (mg/dL)/2]. The non-culprit plaque characteristics were determined by interpreting OCT images in accordance with the standard of previous consensus. Results: 110 patients (54.8 ± 12.1 years, 24.5% female) with 284 non-culprit plaques were included in the current analysis. TyG index was closely associated with high-risk plaque characteristics. Elevated TyG index was consistent to be an independent indicator for thin-cap fibroatheroma (TCFA) [odds ratio (OR) for per 1-unit increase 4.940, 95% confidence interval (CI) 1.652-14.767, P = 0.004; OR for taking lower median as reference 2.747, 95% CI 1.234-7.994, P = 0.011] and ruptured plaque (OR for per 1-unit increase 7.065, 95% CI 1.910-26.133, P = 0.003; OR for taking lower median as reference 4.407, 95% CI 1.208-16.047, P = 0.025) in fully adjusted model. The predictive value of TyG index for TCFA and ruptured plaque was moderate-to-high, with the area under the receiver operating characteristic curve (AUC) of 0.754 and 0.699 respectively. The addition of TyG index into a baseline model exhibited an incremental effect on the predictive value for TCFA, manifested as an increased AUC (0.681, 95% CI 0.570-0.793 vs. 0.782, 95% CI 0.688-0.877, P = 0.042), and significant continuous net reclassification improvement (0.346, 95% CI 0.235-0.458, P < 0.001) and integrated discrimination improvement (0.221, 95% CI 0.017-0.425, P = 0.034). TyG index failed to play an incremental effect on predicting ruptured plaque. Conclusion: TyG index, which is simply calculated from fasting TG and FBG, can be served as an important and independent risk predictor for high-risk non-culprit coronary plaques in patients following ACS.
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BACKGROUND: Measurement of estimated glucose disposal rate (eGDR) has been demonstrated to be an indicator of insulin resistance (IR) and a risk sign for long-term outcomes in those with ischemic heart disease and type 2 diabetes mellitus (T2DM) having coronary artery bypass grafting (CABG). After elective percutaneous coronary intervention (PCI), the usefulness of eGDR for prognosis in those with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and non-diabetes is yet unknown. METHODS: 1510 NSTE-ACS patients with non-diabetes who underwent elective PCI in 2015 (Beijing Anzhen Hospital) were included in this study. Major adverse cardio-cerebral events (MACCEs), such as all-cause mortality, non-fatal myocardial infarction, non-fatal ischemic stroke, and also ischemia-driven revascularization, were the main outcome of follow-up. The average number of follow-up months was 41.84. RESULTS: After multivariate Cox regression tests with confounder adjustment, the occurrence of MACCE in the lower eGDR cluster was considerably higher than in the higher eGDR cluster, demonstrating that eGDR is an independent prognostic indicator of MACCEs. In particular, as continuous variate: hazard ratio (HR) of 1.337, 95% confidence interval (CI) of 1.201-1.488, P < 0.001. eGDR improves the predictive power of usual cardiovascular risk factors for the primary endpoint. Specifically, the results for the area under the receiver operating characteristic (ROC) curve, this is AUC, were: baseline model + eGDR 0.699 vs. baseline model 0.588; P for contrast < 0.001; continuous net reclassification improvement (continuous-NRI) = 0.089, P < 0.001; and integrated discrimination improvement (IDI) = 0.017, P < 0.001. CONCLUSION: Low eGDR levels showed a strong correlation with poor NSTE-ACS prognosis for nondiabetic patients undergoing PCI.
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BACKGROUND: Plaque healing may serve a vital function in the natural progression of atherosclerotic disease. This study sought to investigate predictors and morphological characteristics of healed plaque (HP) among angina pectoris (AP) patients. METHODS: Patients who presented with AP and received preintervention optical coherence tomography (OCT) imaging were consecutively selected for this single-center retrospective observational study. Patient's demographic and clinical information was collected from the hospital's electronic medical records. Coronary angiograms and OCT images were compared via offline software. RESULTS: A total of 390 patients were chosen as the final study population. HP was identified in 186 patients (47.7%) and was relatively less in cases of unstable angina pectoris (UAP) than in stable angina pectoris (SAP) (89/233 [38.2%] vs. 97/157[61.8%]). The HP group had greater prevalence rates of previous myocardial infarction and SAP and higher levels of triglycerides and uremia (median, 1.67 vs. 1.31 mmol/L [p = .01] and 364.22 ± 91.80 vs. 341.53 ± 77.64 µmol/L [p = .01], respectively). Using multivariate analysis, SAP and long lesion length were shown to be stand-alone indicators of HP. HP presented with more severe stenosis as well as a longer lesion length and had more vulnerable and more complex features. In HP lesions, UAP patients had more plaque ruptures and thrombosis, whereas SAP patients had lower uric acid levels and more multiple HPs(≥3 HPs). CONCLUSION: Clinical presentation of SAP and long lesion length were strong predictors for HP in patients with AP. Patients with HP presented with more severe stenosis, longer lesion lengths, greater inflammation, and vulnerability.
Subject(s)
Angina, Stable , Coronary Artery Disease , Plaque, Atherosclerotic , Humans , Coronary Artery Disease/diagnosis , Coronary Artery Disease/diagnostic imaging , Constriction, Pathologic/pathology , Angina, Stable/diagnosis , Angina, Stable/epidemiology , Angina, Stable/pathology , Angina, Unstable/diagnostic imaging , Angina, Unstable/epidemiology , Coronary Angiography , Tomography, Optical Coherence/methods , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathologyABSTRACT
Biofilms formed by bacteria are the group of sessile microbial cells that remain encompassed by self-secreted polymeric substances and have resulted in great health-care concern. The extracellular polymeric substances (EPS) prevent the penetration of antibiotics and other drugs, thereby resulting in the development of multi-drug resistance or antibiotic resistance. The biofilm-associated prosthetics being places at the joins of bone injury are the common sites for the development of biofilm-associated infection. This often spreads and results in the development of orthopaedic infections. Most of the infections are associated with musculoskeletal system and originate from non-living surfaces. The biofilm prevents the penetration of drugs, thereby resulting in the development of antibiotic resistance or multi-drug resistance. The minimum inhibitory concentration (MIC) for allicin and quercetin was found to be 80 µg/mL for quercetin and 100 µg/mL for amoxicillin against the sessile communities of Pseudomonas aeruginosa associated with the orthopaedic infection. The role of quercetin and allicin in reduction of protein, carbohydrate and eDNA content of the exopolysaccharides (EPS) was tested. The anti-quorum sensing activity of quercetin and allicin was confirmed both by biochemical and by photomicrographic studies. The antibiofilm and antimicrobial activities of quercetin and allicin were determined both by in vitro and in silico studies on P. aeruginosa bacterial strain from biofilm-associated orthopaedic infection.