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The genetic information of plasma total-exosomes originating from tissues have already proven useful to assess the severity of coronary artery diseases (CAD). However, plasma total-exosomes include multiple sub-populations secreted by various tissues. Only analysing the genetic information of plasma total-exosomes is perturbed by exosomes derived from other organs except the heart. We aim to detect early-warning biomarkers associated with heart-exosome genetic-signatures for acute myocardial infarction (AMI) by a source-tracking analysis of plasma exosome. The source-tracking of AMI plasma total-exosomes was implemented by deconvolution algorithm. The final early-warning biomarkers associated with heart-exosome genetic-signatures for AMI was identified by integration with single-cell sequencing, weighted gene correction network and machine learning analyses. The correlation between biomarkers and clinical indicators was validated in impatient cohort. A nomogram was generated using early-warning biomarkers for predicting the CAD progression. The molecular subtypes landscape of AMI was detected by consensus clustering. A higher fraction of exosomes derived from spleen and blood cells was revealed in plasma exosomes, while a lower fraction of heart-exosomes was detected. The gene ontology revealed that heart-exosomes genetic-signatures was associated with the heart development, cardiac function and cardiac response to stress. We ultimately identified three genes associated with heart-exosomes defining early-warning biomarkers for AMI. The early-warning biomarkers mediated molecular clusters presented heterogeneous metabolism preference in AMI. Our study introduced three early-warning biomarkers associated with heart-exosome genetic-signatures, which reflected the genetic information of heart-exosomes carrying AMI signals and provided new insights for exosomes research in CAD progression and prevention.
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Biomarcadores , Exossomos , Infarto do Miocárdio , Exossomos/genética , Exossomos/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/diagnóstico , Humanos , Feminino , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Transcriptoma/genéticaRESUMO
BACKGROUND In China, the most prevalent type of CRKP is ST11, but the high-risk clone ST15 has grown in popularity in recent years, posing a serious public health risk. Therefore, we investigated the molecular prevalence characteristics of ST15 CRKP detected in a tertiary hospital in Ningbo to understand the current potential regional risk of ST15 CRKP outbreak. MATERIAL AND METHODS We collected and evaluated 18 non-duplicated CRKP strains of ST15 type for antibiotic resistance. Their integrons, virulence genes, and resistance genes were identified using polymerase chain reaction (PCR), and their homology was determined using MALDI-TOF MS. RESULTS The predominant serotype of 18 ST15 CRKP strains was K5. ST15 CRKP exhibited the lowest antimicrobial resistance to Cefoperazone/sulbactam (11.1%), followed by trimethoprim/sulfamethoxazole (22.2%). Resistance gene testing revealed that 14 out of 18 ST15 CRKP strains (77.8%) carried Klebsiella pneumoniae carbapenemase 2 (KPC-2), whereas all ST15 CRKP integrons were of the intI1 type. Furthermore, virulence gene testing revealed that all 18 ST15 CRKP strains carried ybtS, kfu, irp-1, and fyuA genes, followed by the irp-2 gene (17 strains) and entB (16 strains). The homology analysis report showed that 2 clusters had closer affinity, which was mainly concentrated in classes C and D. CONCLUSIONS The ST15 CRKP antibiotic resistance rates demonstrate clear geographical differences in Ningbo. Additionally, some strains carried highly virulent genes, indicating a possible evolution towards carbapenem-resistant highly virulent strains. To reduce the spread of ST15 CRKP, we must rationalize the clinical use of antibiotics and strengthen resistance monitoring to control nosocomial infections.
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Antibacterianos , Carbapenêmicos , Infecções por Klebsiella , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Centros de Atenção Terciária , China/epidemiologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Humanos , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Prevalência , Integrons/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , beta-Lactamases/genética , beta-Lactamases/metabolismo , Farmacorresistência Bacteriana/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacosRESUMO
BACKGROUND & AIMS: The Baveno VII consensus recommends that spleen stiffness measurement (SSM) ≤40 kPa is safe for ruling out high-risk varices (HRVs) and avoiding endoscopic screening in patients who do not meet the Baveno VI criteria. This study aimed to validate the performance of the Baveno VII algorithm in individuals with HBV-related cirrhosis. METHODS: Consecutive individuals with HBV-related cirrhosis who underwent liver stiffness measurement (LSM) and SSM - using a 50 Hz shear wave frequency, spleen diameter measurement, and esophagogastroduodenoscopy (EGD) were prospectively enrolled from June 2020. A 100 Hz probe has been adopted for additional SSM assessment since July 2021. RESULTS: From June 2020 to January 2022, 996 patients were screened and 504 were enrolled for analysis. Among the 504 patients in whom SSM was assessed using a 50 Hz probe, the Baveno VII algorithm avoided more EGDs (56.7% vs. 39.1%, p <0.001) than Baveno VI criteria, with a comparable missed HRV rate (3.8% vs. 2.5%). Missed HRV rates were >5% for all other measures: 11.3% for LSM-longitudinal spleen diameter to platelet ratio score, 20.0% for platelet count/longitudinal spleen diameter ratio, and 8.8% for Rete Sicilia Selezione Terapia-hepatitis. SSM@100 Hz was assessed in 232 patients, and the Baveno VII algorithm with SSM@100 Hz spared more EGDs (75.4% vs. 59.5%, p <0.001) than that with SSM@50 Hz, both with a missed HRV rate of 3.0% (1/33). CONCLUSIONS: We validated the Baveno VII algorithm, demonstrating the excellent performance of SSM@50 Hz and SSM@100 Hz in ruling out HRV in individuals with HBV-related cirrhosis. Furthermore, the Baveno VII algorithm with SSM@100 Hz could safely rule out more EGDs than that with SSM@50 Hz. CLINICAL TRIAL NUMBER: NCT04890730. IMPACT AND IMPLICATIONS: The Baveno VII guideline proposed that for patients who do not meet the Baveno VI criteria, SSM ≤40 kPa could avoid further unnecessary endoscopic screening. The current study validated the Baveno VII algorithm using 50 Hz and 100 Hz probes, which both exhibited excellent performance in ruling out HRVs in individuals with HBV-related cirrhosis. Compared with the Baveno VII algorithm with SSM@50 Hz, SSM@100 Hz had a better capability to safely rule out unnecessary EGDs. Baveno VII algorithm will be a practical tool to triage individuals with cirrhosis in future clinical practice.
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Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas , Varizes , Humanos , Vírus da Hepatite B , Cirrose Hepática/diagnóstico , AlgoritmosRESUMO
BACKGROUND: The development of coagulation disorders can be dangerous and fatal in the older people, especially those with multiple medical conditions. Vitamin K-dependent coagulation disorders are easily overlooked when anticoagulant drugs are not used and the patient shows no signs of bleeding. CASE PRESENTATION: We report a case of a 71-year-old male suffering from pulmonary infection with severe coagulation disorder without bleeding symptoms. He also had a history of Parkinson's disease, Alzheimer's disease and cardiac insufficiency. Coagulation tests were normal at the time of admission, prothrombin time (PT) is 13.9 (normal, 9.5-13.1) seconds and the activated partial thromboplastin time (APTT) is 30.2 (normal, 25.1-36.5) seconds. But it turned severely abnormal after 20 days (PT: 136.1 s, APTT: 54.8 s). However, no anticoagulants such as warfarin was used and no bleeding symptoms were observed. Subsequent mixing studies with normal plasma showed a decrease in prothrombin times. Vitamin K deficiency was thought to be the cause of coagulation disorders considering long-term antibiotic therapy, especially cephalosporins, inadequate diet and abnormal liver function. After supplementation with 20 mg of vitamin K, coagulation dysfunction was rescued the next day and serious consequences were effectively prevented. CONCLUSIONS: Overall, timely vitamin K supplementation with antimicrobials that affect vitamin K metabolism requires clinician attention, especially in older patients who are multimorbid, frail or nutritionally compromised, and are admitted to hospital because of an infection that needs antimicrobial therapy are at risk of clotting disorders due to abnormal vitamin K metabolism secondary to altered gut flora, which can exacerbate existing nutritional deficiencies.
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Transtornos da Coagulação Sanguínea , Pneumonia , Deficiência de Vitamina K , Idoso , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Coagulação Sanguínea , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/etiologia , Humanos , Masculino , Pneumonia/complicações , Vitamina K , Deficiência de Vitamina K/complicações , Deficiência de Vitamina K/diagnóstico , Deficiência de Vitamina K/tratamento farmacológicoRESUMO
BACKGROUND & AIMS: There are no data validating the performance of spleen stiffness measurement in ruling out high-risk varices in patients with HBV-related cirrhosis under maintained viral suppression. Thus, we aimed to prospectively validate the performance of spleen stiffness measurement (cut-off 46 kPa) combined with Baveno VI criteria in ruling out high-risk varices in these patients. METHODS: Patients with cirrhosis were enrolled from April to December 2019 at the hepatology unit of the Nanfang Hospital, China. Liver and spleen transient elastography and esophagogastroduodenoscopy were performed at enrollment. Antiviral regimen(s) and virological responses, evaluated every 3-6 months, were recorded. RESULTS: Overall 341 patients with HBV-related cirrhosis under maintained viral suppression were enrolled, and the prevalence of high-risk varices was 20.5% (70/341). Baveno VI criteria spared 37.0% (126/341) esophagogastroduodenoscopies and no high-risk varices were missed (0/70). Eight cases of high-risk varices (8/70, 11.4%) were misclassified in patients (208/341, 61.0%) within the expanded Baveno VI criteria. The spleen stiffness measurement cut-off (≤46.0 kPa) was shown to safely rule out high-risk varices in these patients (the percentage of missed high-risk varices was 4.3%). Over half (61.6%, 210/341) of patients met the combined model (Baveno VI criteria and spleen stiffness measurement cut-off ≤46 kPa) and 4.3% (3/70) of high-risk varices cases were misclassified. This combined model exhibited a sensitivity of 95.71%, specificity of 76.38%, negative predictive value of 98.57%, and negative likelihood ratio of 0.06 for ruling out high-risk varices. CONCLUSIONS: We validated the excellent performance of Baveno VI criteria combined with spleen stiffness measurement (cut-off 46 kPa) for safely ruling out high-risk varices in patients with HBV-related cirrhosis under viral suppression; more than half of esophagogastroduodenoscopy procedures were spared using this combination. CLINICAL TRIAL NUMBER: NCT04123509 LAY SUMMARY: Esophageal varices have important prognostic implications in patients with cirrhosis. Thus, their timely identification is important so that treatment can be initiated early. Herein, we validated the excellent performance of the combination of Baveno VI criteria with spleen stiffness measurement (cut-off 46 kPa) for ruling out high-risk esophageal varices in patients with HBV-related cirrhosis under maintained viral suppression (with antiviral treatment). This combined model was able to safely rule out high-risk varices (missed/total <5%) and over half (61.6%) of esophagogastroduodenoscopy procedures were spared.
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Antivirais/uso terapêutico , Elasticidade , Varizes Esofágicas e Gástricas/epidemiologia , Varizes Esofágicas e Gástricas/etiologia , Vírus da Hepatite B/genética , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Cirrose Hepática/complicações , Baço/patologia , Adulto , China/epidemiologia , DNA Viral/genética , Técnicas de Imagem por Elasticidade , Feminino , Hepatite B/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Resposta Viral SustentadaRESUMO
BACKGROUND & AIMS: The role of cigarette smoking in the development of chronic hepatitis B (CHB) remains poorly understood. We assessed the potential contributions of cigarette smoking to liver fibrosis and its regression after starting antiviral therapy in CHB patients. METHODS: In this cohort study, 2144 consecutive male CHB patients under no antiviral therapy were evaluated and 206 patients with significant liver fibrosis (≥F2) initiating antiviral therapy had longitudinal follow-up. Liver fibrosis was measured by liver stiffness measurement using transient elastography. To adjust for imbalances between smoking history and never smoking groups, propensity score (PS) matching model with 1:1 ratios were performed. Cigarette smoking history and intensity (pack-years) were collected and documented using a standardized questionnaire. RESULTS: Before PS matching, 432/2144 patients had advanced fibrosis in prevalence cohort. Patients with smoking history (n = 1002) had a greater prevalence of advanced fibrosis than those without (n = 1142) (24.4% vs 16.5%, P = 0.001). Multivariate logistic regression analysis demonstrated that smoking contributed to advanced fibrosis (OR, 1.458; 95% CI, 1.114-1.908). In longitudinal cohort, multivariate logistic regression analysis demonstrated retarded fibrosis regression in patients with history of smoking ≥10 pack-years (OR, 0.288; 95% CI, 0.1-0.825). After PS matching, patients with smoking history had higher prevalence of advanced fibrosis (22.8% vs 18%, P = 0.024) than those non-smokers. In post-PS-matching logistic regression, the effect of smoking on advanced fibrosis persisted (OR, 1.415; 95% CI, 1.047-1.912; P = 0.024). CONCLUSIONS: Cigarette smoking in male CHB patients aggravated liver fibrosis prior to and delayed fibrosis regression under antiviral therapy.
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Antivirais/uso terapêutico , Fumar Cigarros/efeitos adversos , Hepatite B Crônica/complicações , Cirrose Hepática/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Progressão da Doença , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Background: Klebsiella pneumoniae (KP) is a common nosocomial pathogen. Capsules are an important component of KP's virulence, among which the K1, K2, K5, K20, K54, and K57 serotypes are predominant and exhibit varying degrees of virulence. Methods: The capsule and virulence genes of 150 carbapenem-resistant Klebsiella pneumoniae (CRKP) and 213 carbapenem-sensitive Klebsiella pneumoniae (CSKP) isolates were examined by polymerase chain reaction (PCR). The isolates were tested for hypermucoviscosity by string tests. Phylogenetic relationships between KP isolates were analyzed using multilocus sequence typing (MLST) and a Galleria mellonella infection model confirmed the differences in virulence. Results: A total of 111 of 363 isolates of KP were detected, the highest detected serotypes were K1, K5, and K2, and CSKP was detected more frequently than CRKP. There was a greater prevalence of K1 and K2 serotypes in CSKP, while in CRKP, K5 serotypes were more prevalent. K1 isolates had the highest detection rates for hypermucoviscosity Klebsiella pneumoniae (hmKP) and hypervirulent Klebsiella pneumoniae (hvKP), and carried the most virulence genes. K54 isolates had the lowest detection rate of hmKP while K5 isolates had the lowest detection rate of hvKP and carried the fewest virulence genes. MLST results for serotypes K1, K20, and K57 showed significant homogeneity, while those for serotypes K2, K5, and K54 showed diversity. The Galleria mellonella infection model showed that the K1 serotype was the most virulent and the K54 serotype was the weakest. Conclusion: CSKP isolates were detected more frequently than CRKP isolates for capsular serotype detection. K1 isolates had the most virulence gene and strongest virulence, K5 isolates carried the fewest virulence genes, and K54 isolates had the weakest virulence. Furthermore, significant homogeneity was observed among K1, K20, and K57 isolates.
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Background: In recent years, Klebsiella pneumoniae has attracted attention because of its increasing drug resistance. At the same time, the migration and pathogenicity caused by its virulence genes also bring many difficulties to the diagnosis and treatment of clinical infections. However, it is currently unclear whether there are differences in virulence and pathogenicity with changes in drug resistance. Objective: To understand the differences in molecular characteristics and expression of virulence genes in carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-sensitive Klebsiella pneumoniae (CSKP). Methods: Using polymerase chain reaction (PCR), we examined capsule polysaccharide-related genes and virulence genes in 150 clinical isolates of CRKP and 213 isolates of CSKP from the local area in Ningbo, China. Multilocus sequence typing (MLST) was used to analyze the phylogenetic relationships of clinical Klebsiella pneumoniae isolates. Furthermore, real-time quantitative PCR (RT-qPCR) was used to analyze the expression differences of common virulence genes in CSKP and CRKP, and the virulence was further verified by the larval model of Galleria mellonella. Results: The study found that the detection rates of genes rmpA, iroB, peg-344, magA, aerobactin, alls, kfu, and entB were significantly higher in CSKP compared to CRKP. The capsule gene types K1 and K2 were more common in CSKP, while K5 was more common in CRKP. Hypervirulent Klebsiella pneumoniae (hvKP) was predominantly from CSKP. CRKP strains exhibited noticeable homogeneity, with ST11 being the predominant sequence type among the strains. CSKP strains showed greater diversity in ST types, but ST23 was still the predominant sequence type. Carbapenem-sensitive hypervirulent Klebsiella pneumoniae (CS-hvKP) had higher expression of rmpA and rmpA2 genes compared to carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP). In the wax moth virulence model, the survival rate of CS-hvKP was significantly lower than that of CR-hvKP. Conclusion: There is a significant difference in the distribution of virulence genes between CSKP and CRKP, with CSKP carrying a significantly greater number of virulence genes. Furthermore, compared to CSKP, CRKP strains exhibit noticeable homogeneity, with ST11 being the predominant sequence type among the strains. Additionally, in terms of virulence gene expression efficiency and virulence, CSKP is significantly higher than CRKP.
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BACKGROUND: Esophagogastroduodenoscopy (EGD) is required to screen for high-risk varices (HRV) in patients with hepatocellular carcinoma (HCC), especially since overall survival rates have dramatically improved with new systemic therapies. AIM: To assess the Baveno VI and Baveno VII algorithms' ability to rule out HRV in hepatitis B virus (HBV)-related HCC METHODS: We prospectively enrolled consecutive patients with HBV related, compensated cirrhosis and newly diagnosed HCC who underwent liver stiffness measurement, spleen stiffness measurement (SSM) using a 100-Hz shear wave frequency, and EGD. RESULTS: From September 2021 to August 2023, we enrolled 219 patients with HCC, with 107 (48.9%) Barcelona Clinic Liver Cancer (BCLC) A, 28 (12.8%) BCLC B and 84 (38.3%) BCLC C, respectively. HRV prevalence was 28.8% (63/219). Baveno VI criteria safely (HRV missing rate, 3.2%) avoided 27.4% unnecessary EGDs, while the Baveno VII algorithm avoided 49.3% with HRV missing rate at 7.9% (5/63). The SSM ≤40 kPa avoided 47.5% of EGDs safely (HRV missing rate, 4.8%), significantly better than the Baveno VI criteria (p < 0.001) and comparable to the Baveno VII algorithm (p = 0.390). The SSM ≤40 kPa safely avoided EGDs in patient subgroups within Milan criteria, with portal vein tumour thrombosis or BCLC B/C or candidates for systemic therapy. CONCLUSIONS: We validated that the SSM ≤40 kPa using a 100-Hz probe could safely eliminate more unnecessary EGDs than the Baveno VI criteria in patients with HBV-related HCC. However, the efficacy of the Baveno VII algorithm in patients with HCC requires further investigation.
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Carcinoma Hepatocelular , Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas , Neoplasias Hepáticas , Varizes , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Vírus da Hepatite B , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Baço/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico , Cirrose Hepática/complicações , Cirrose Hepática/diagnósticoRESUMO
This novel spleen-dedicated FibroScan has high success rate and is easy to operate. The spleen stiffness is correlated with liver stiffness, which reflects the liver fibrosis stage. However, whether SSM is able to reflect the severity of liver disease warrants further observation.
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BACKGROUND: Integrons are the main mode of horizontal transmission of drug-resistance genes and are closely related to drug resistance in clinical bacteria. In this study, the distributions of class 1, 2, and 3 integron gene cassettes were investigated in 150 Proteus mirabilis (P. mirabilis) isolates from patients, and molecular characterization of functional class 2 integrons was further analyzed. METHODS: Class 1, 2, and 3 integrons were screened by polymerase chain reaction (PCR) in 150 clinical P. mirabilis isolates. The variable regions of the integrons were determined by restriction analysis and sequencing. Internal stop codons mutations in class 2 integrons and their common promoters were also determined by sequencing. Enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) was used to analyze the phylogenetic relations of class 2 integron-positive isolates. RESULTS: Class 1 integrons were detected in 69 (46%) of 150 P. mirabilis isolates, and six different gene cassette arrays were detected, with the most prevalent being dfrA32-aadA2. Class 2 integrons were detected in 61 (40.7%) of 150 P. mirabilis isolates, and three different gene cassette arrays were detected, including sat2-aadA1, which was detected for the first time in a class 2 integron. Nearly similar ERIC-PCR fingerprinting patterns were detected in 45 (73.8%) of 61 class 2 integron-positive isolates. The functional class 2 integron was detected in three P. mirabilis isolates having the same gene cassette, dfrA1-sat2-aadA1, in the variable region and four novel open reading frames with unknown functions. Same PintI2 and Pc promoters were detected in these three functional class 2 integron isolates, as was found in other class 2 integron isolates. However, these three strains did not totally show identical homology and drug sensitivity. CONCLUSION: Although functional class 2 integrons have low distribution and relatively conserved molecular characteristics, they can still form clinical dissemination and drug resistance expression.
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Listeria monocytogenes (LM) is a foodborne pathogen, and it can pose a risk of serious diseases to the human health. Hence, the development of an effective method for the detection of LM is very important. In this study, by selecting LM as the template and 3-thiopheneacetic acid as the functional monomer, an LM-imprinted polymer (LIP)-based sensor was proposed for the first time to detect LM by electropolymerizing TPA on the glassy carbon electrode (GCE) surface in the presence of LM. After the removal of the LM template from the electrode surface, the obtained sensor was denoted as LIP/GCE, which could effectively recognize and capture LM cells. By using [Fe(CN)6]4-/3- as the probe, its peak current at LIP/GCE could be restricted when the LM cells were captured into the imprinted cavity of LIP/GCE, and the current value decreased with an increase in the LM concentration. Serious conditions were optimized for achieving highly sensitive detection, and a low detection limit (6 CFU mL-1) coupled with a wide linear range (10 to 106 CFU mL-1) was obtained for LM. Finally, the inter-electrode reproducibility, stability, selectivity, and applicability of LIP/GCE were also investigated, and the obtained results were acceptable.
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Listeria monocytogenes , Impressão Molecular , Técnicas Eletroquímicas , Eletrodos , Humanos , Limite de Detecção , Polímeros , Reprodutibilidade dos TestesRESUMO
Hemoglobin (Hb) plays an important role in oxygen carriage for mammals, which is also a typical biomarker for certain diseases. Although numerous methods had been developed for the detection of Hb in red blood cells, analytical technology for the monitoring of low-abundance Hb in serum or plasma is still a challenge. Herein, persistent luminescence nanoparticles (PLNPs) with strong near-infrared (NIR) emission character behaving as a label-free probe for the highly sensitive and selective detection of Hb were developed. Further studies revealed that the sensing mechanism should be attributed to the Hb-induced dynamic quenching process. Moreover, the nanoprobe showed high selectivity to Hb against the common existing substances in human serum and a linear response to Hb ranging from 1 to 50â¯nM with an extremely high limit of detection (LOD) of 0.13â¯nM. Finally, applicability of the proposed probe for the detection of Hb in human serum samples was validated.
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Hemoglobinas/análise , Substâncias Luminescentes/química , Nanopartículas Metálicas/química , Cromo/química , Gálio/química , Humanos , Limite de Detecção , Luminescência , Medições Luminescentes/métodos , Tamanho da Partícula , Zinco/químicaRESUMO
BACKGROUND: Lung adenocarcinoma (LA) is a most common form of non-small cell lung cancer (NSCLC). To date, there are still no effective early diagnosis methods for patients to be cured in time. Noncoding RNA plays an important role in oncogenesis and tumor development. The expression profile of circular RNA (circRNA) in peripheral whole blood (PWB) of LA has not been systematically investigated. In this study, we identified the differentially expressed (DE) circRNAs in PWB of LA by high-throughput sequencing. METHODS: Five paired LA and normal participants PWB samples were chosen to investigate the expression profile of circRNAs by high-throughput sequencing. Twenty LA and 10 normal controls PWB samples were subjected to reverse-transcription polymerase chain reaction (RT-PCR) for validation of circRNAs expression profile. Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and circRNA-miRNA network analysis was also performed to predict the function of circRNAs in PWB. RESULTS: A total of 10566 circRNAs were identified and annotated, most of the circRNAs were exonic (78.14%). Statistical analysis revealed 4390 DE circRNAs, in which were 3009 upregulated circRNAs and1381downregulated circRNAs in LA. RT-PCR results showed that circRNA expression in LA was higher than that in controls. GO functional analysis, KEGG pathway analysis, and circRNA-miRNA network analysis all showed that circRNAs correlated with tumor development and progression to a certain degree. The current study is the first to systematically characterize and annotate circRNA expression in PWB of LA. Some host genes of the DE circRNAs were involved in tumor signaling pathway and had complicated correlations with tumor related miRNAs, indicating that circRNAs might involve in development and progression of LA. CONCLUSIONS: Our study revealed that circRNAs were abnormally expressed in PWB of LA, which might offer potential targets for the early diagnosis of the disease and new genetic insights into LA.
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Adenocarcinoma de Pulmão/genética , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , RNA/genética , Adenocarcinoma de Pulmão/sangue , Perfilação da Expressão Gênica/métodos , Humanos , RNA/biossíntese , RNA Circular , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Regulação para CimaRESUMO
INTRODUCTION: The role of reproductive factors in the development of chronic hepatitis B (CHB) remains unknown. We assessed the potential contributions of gender, menopausal status, and menarche age to liver fibrosis in CHB. METHODS: A cross-sectional prospective study included 716 women and 716 age-matched men with CHB who were not currently receiving antiviral therapy. Liver stiffness measurement using transient elastography was used to stage liver fibrosis as F0-F1 (<7.2 kPa), F ≥ 2 (7.2 kPa), F ≥ 3 (9.4 kPa), and F = 4 (12.2 kPa). Female patients were asked regarding their age at menarche and menopausal status using a questionnaire. RESULTS: Of the 716 women, 121 (16.9%) were postmenopausal, and 80 (11.2%) had advanced liver fibrosis. Multivariate logistic regression analysis showed that the postmenopausal status compared with the premenopausal status (odds ratio [OR] = 3.65-8.83; P < 0.05) and age at menarche of >14 years compared with <13 years (OR = 2.85-3.95; P < 0.05) were significantly associated with advanced fibrosis. Compared with premenopausal women, age-matched men had a higher OR for advanced fibrosis (P < 0.05). Compared with postmenopausal women, age-matched men did not show a significant difference in the degree of liver fibrosis (P > 0.05). Longitudinal data analysis showed that postmenopausal women (n = 31) were significantly less likely to undergo regression of liver fibrosis after antiviral treatment vs premenopausal women (n = 19) (26.3% vs 74.2%, respectively; P < 0.001). DISCUSSION: Menopause and late menarche aggravated liver fibrosis in untreated CHB, besides menopause delayed fibrosis regression under antiviral therapy. The protective effect of female gender against fibrosis was lost for postmenopausal women. TRANSLATIONAL IMPACT: It is important to consider menopausal status and age at menarche in establishing surveillance strategies among CHB females. Postmenopausal estrogen therapy may be considered for the prevention or treatment of liver fibrosis.
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Hepatite B Crônica/patologia , Cirrose Hepática/epidemiologia , Fígado/patologia , História Reprodutiva , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biópsia , Estudos Transversais , Progressão da Doença , Técnicas de Imagem por Elasticidade , Feminino , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática/diagnóstico , Cirrose Hepática/fisiopatologia , Cirrose Hepática/terapia , Estudos Longitudinais , Masculino , Menarca/fisiologia , Pessoa de Meia-Idade , Pós-Menopausa/fisiologia , Estudos Prospectivos , Curva ROC , Fatores Sexuais , Adulto JovemRESUMO
OBJECTIVE: To explore the diagnostic value of the measurement of serum Golgi protein 73 (GP73) in the diagnosis of hepatocellular carcinoma (HCC). METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum GP73 in the 81 cases of HCC, 71 cases of chronic hepatitis or cirrhosis (CH/LC) and 65 cases of healthy blood donors, and to evaluate the sensitivity and specificity in the diagnosis of HCC through the ROC curves. RESULTS: The average levels of serum GP73 in HCC, CH/LC and Normal groups were (152.67 +/- 33.59) ng/ml, (93.15 +/- 20.02) ng/ml and (58.95 +/- 17.29) ng/ml(o) After calculating through the ROC curves, 120 ng/ml was set as the optimal cut-off point, GP73 has a sensitivity of 77.80% and a specificity of 78.00%. CONCLUSIONS: GP73 as a serum marker in the diagnosis of HCC had a higher sensitivity than AFP, and the combined detection of GP73 and AFP could improve HCC diagnosis.
Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Proteínas de Membrana/sangue , alfa-Fetoproteínas/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Cirrose Hepática/sangue , MasculinoRESUMO
Aims: Diabetes has become a major public health problem in China. Recent advances in genetic studies have identified numerous susceptibility loci for type 2 diabetes (T2D). Current models to detect risk of T2D are largely based on studies from European populations; this study aims to replicate those efforts in a Chinese population from the Ningbo region in order to diversify and fortify risk models. Methodology: We successfully genotyped 11 single nucleotide polymorphisms (SNPs) in 222 subjects with T2D and 140 subjects with normal glucose regulation in a population from the Ningbo region of China. Additive and dominant models were used to analyze the associations between SNPs and T2D. Results: Adjusting for age, triglycerides, total cholesterol, low density lipoprotein, and BMI in the dominant model, we identified three SNPs which were associated T2D: CDKAL1 (OR=2.29 [95%CI=1.25-4.19]), KCNQ1 (4.22 [1.79-9.99]), and IGF2BP2 (1.76 [1.06-2.94]). No significant association was found between T2D and SNPs from KCNJ11, PPARG, TCF7L2, SALC30A8, CDKN2B, HHEX, HNF1β, and WFS1. Conclusion: Our data indicates that in this population, CDKAL1, KCNQ1, and IGF2BP2 are T2D susceptibility genes.