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Background: Non-small cell lung cancer (NSCLC), including the lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) subtypes, is a malignant tumor type with a poor 5-year survival rate. The identification of new powerful diagnostic biomarkers, prognostic biomarkers, and potential therapeutic targets in NSCLC is urgently required. Methods: The UCSC Xena, UALCAN, and GEO databases were used to screen and analyze differentially expressed genes, regulatory modes, and genetic/epigenetic alterations in NSCLC. The UCSC Xena database, GEO database, tissue microarray, and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values. Gain-of-function assays were performed to examine the roles. The ESTIMATE, TIMER, Linked Omics, STRING, and DAVID algorithms were used to analyze potential molecular mechanisms. Results: NR3C2 was identified as a potentially important molecule in NSCLC. NR3C2 is expressed at low levels in NSCLC, LUAD, and LUSC tissues, which is significantly related to the clinical indexes of these patients. Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC, LUAD, and especially LUSC patients. Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients. These results have been confirmed both with database analysis and real-world clinical samples on a tissue microarray. Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD, while promoter DNA methylation is involved in its downregulation in LUSC. Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential. NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration. NR3C2 co-expressed genes are involved in many cancer-related signaling pathways, further supporting a potentially significant role of NR3C2 in NSCLC. Conclusions: NR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.
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BACKGROUND: This study aimed to quantify the global stroke burden attributable to low physical activity and high body mass index in adults aged ≥55 years using data from the Global Burden of Disease 2019 study. METHODS: We extracted data on stroke mortality, disability-adjusted life years, and risk factor exposure from the Global Burden of Disease 2019 study for people aged ≥55 years. We calculated the population-attributable fraction and absolute number of stroke cases and disability-adjusted life years attributable to low physical activity and high body mass index by location, age group, sex, and year. RESULTS: Globally, body mass index and physical inactivity-attributable stroke burden have declined modestly since 1990, but with diverging escalatory regional trajectories. Population growth and aging drive this rising burden. CONCLUSIONS: Multidimensional, context-specific strategies focused on modifiable lifestyle risks are imperative to address the modest declines and escalatory regional trajectories in body mass index and physical inactivity-attributable stroke burden.
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Índice de Massa Corporal , Exercício Físico , Acidente Vascular Cerebral , Humanos , Masculino , Idoso , Feminino , Acidente Vascular Cerebral/epidemiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Carga Global da Doença , Fatores de Risco , Anos de Vida Ajustados por Deficiência , Comportamento SedentárioRESUMO
BACKGROUND: Accumulating evidence suggests a pivotal role of vitamin B2 in the pathogenesis and progression of prostate cancer (PCa). Vitamin B2 intake has been postulated to modulate the screening rate for PCa by altering the concentration of prostate-specific antigen(PSA). However, the relationship between vitamin B2 and PSA remains indeterminate. Hence, we conducted a comprehensive evaluation of the association between vitamin B2 intake and PSA levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: From a pool of 20,371 participants in the NHANES survey conducted between 2003 and 2010, a cohort of 2,323 participants was selected for the present study. The male participants were classified into four distinct groups based on their levels of vitamin B2 intake. We employed a multiple linear regression model and a non-parametric regression method to investigate the relationship between vitamin B2 and PSA levels. RESULTS: The study cohort comprised of 2,323 participants with a mean age of 54.95 years (± 11.73). Our findings revealed a statistically significant inverse correlation between vitamin B2 intake (mg) and PSA levels, with a reduction of 0.13 ng/ml PSA concentration for every unit increase in vitamin B2 intake. Furthermore, we employed a fully adjusted model to construct a smooth curve to explore the possible linear relationship between vitamin B2 intake and PSA concentration. CONCLUSIONS: Our study in American men has unveiled a notable inverse association between vitamin B2 intake and PSA levels, potentially posing a challenge for the identification of asymptomatic prostate cancer. Specifically, our findings suggest that individuals with higher vitamin B2 intake may be at a greater risk of being diagnosed with advanced prostate cancer in the future, possibly indicating a detection bias. These results may offer a novel explanation for the observed positive correlation between vitamin B2 intake and prostate cancer.
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Inquéritos Nutricionais , Antígeno Prostático Específico , Neoplasias da Próstata , Riboflavina , Humanos , Masculino , Antígeno Prostático Específico/sangue , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Idoso , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Riboflavina/administração & dosagem , AdultoRESUMO
OBJECTIVE: This modelling study aimed to estimate the burden for allergic diseases in children during a period of 30 years. DESIGN: Population-based observational study. MAIN OUTCOMES AND MEASURES: The data on the incidence, mortality and disability-adjusted life years (DALYs) for childhood allergic diseases, such as atopic dermatitis (AD) and asthma, were retrieved from the Global Burden of Disease study 2019 online database. This data set spans various groups, including different regions, ages, genders and Socio-Demographic Indices (SDI), covering the period from 1990 to 2019. RESULTS: In 2019, there were approximately 81 million children with asthma and 5.6 million children with AD worldwide. The global incidence of asthma in children was 20 million. Age-standardised incidence rates showed a decrease of 4.17% for asthma, from 1075.14 (95% uncertainty intervals (UI), 724.63 to 1504.93) per 100 000 population in 1990 to 1030.33 (95% UI, 683.66 to 1449.53) in 2019. Similarly, the rates for AD decreased by 5.46%, from 594.05 (95% UI, 547.98 to 642.88) per 100 000 population in 1990 to 561.61 (95% UI, 519.03 to 608.29) in 2019. The incidence of both asthma and AD was highest in children under 5 years of age, gradually decreasing with age. Interestingly, an increase in SDI was associated with a rise in the incidence of both conditions. However, the mortality rate and DALYs for asthma showed a contrasting trend. CONCLUSIONS: Over the past three decades, there has been a worldwide increase in new asthma and AD cases, even though mortality rates have significantly declined. However, the prevalence of these allergic diseases among children varies considerably across regions, countries and age groups. This variation highlights the need for precise prevalence assessments. These assessments are vital in formulating effective strategies for prevention and treatment.
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Asma , Dermatite Atópica , Criança , Humanos , Masculino , Feminino , Pré-Escolar , Carga Global da Doença , Anos de Vida Ajustados por Qualidade de Vida , Prevalência , Incidência , Asma/epidemiologia , Dermatite Atópica/epidemiologia , Saúde Global , Fatores de RiscoRESUMO
Epilepsy is a profound disorder, accounting for roughly 1% of the global disease burden. It can result in premature death and significant disability. To comprehensively understand the current dynamics and trends of idiopathic epilepsy, a deep insight into its epidemiological attributes is vital. We evaluated the incidence, prevalence, mortality, and disability-adjusted life years associated with idiopathic epilepsy from 1990 to 2019 using data and methodologies from the Global Burden of Disease Study. In 2019, there were approximately 2,898,222 individuals diagnosed with idiopathic epilepsy. Intriguingly, from 1990 to 2019, the age-standardized incidence rate of idiopathic epilepsy was consistently lower in women compared to men. Over these three decades, global mortality connected to idiopathic epilepsy increased by 13.95%. However, within the same period, age-standardized death rates for idiopathic epilepsy decreased from 1.94 per 100,000 population to 1.46 per 100,000 population. Predictions indicate an increase in the incidence of idiopathic epilepsy across all age brackets through 2035, especially among the elderly aged 80 and above. Mortality rates are projected to climb for those aged 80 and above while remaining relatively unchanged in other age demographics. Idiopathic epilepsy continues to be a significant contributor to both disability and death. The findings of our study underscore the critical importance of incorporating idiopathic epilepsy management into modern healthcare frameworks. Such strategic inclusion can enhance public awareness of relevant risk factors and the range of available therapeutic interventions.
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BACKGROUND: Hydrocephalus following dural tear after spinal surgery is rare. Although a few cases of obstructive hydrocephalus caused by subdural fluid collection and communicating hydrocephalus associated with meningitis have been reported, the mechanism remains uncertain. Herein we describe a patient complicated with hydrocephalus after cervical laminoplasty in whom subdural fluid collection in the cervical spine and posterior cranial fossa rather than chronic meningitis was the main mechanism. CASE SUMMARY: A 45-year-old man underwent cervical laminoplasty for cervical spondylotic myelopathy at a local hospital. Ten days postoperatively, a high fever occurred and magnetic resonance imaging (MRI) showed cerebrospinal fluid (CSF) leakage. Pseudomeningocele liquid test showed high levels of protein and white blood cell (WBC) count with negative bacterial culture. The patient was treated with short-term intravenous antibiotic and discharged with normal body temperature. The patient was uneventful during the first 8 mo follow-up although repeated MRI showed persistent pseudomeningocele. At the 9th mo postoperatively, the patient gradually presented with dizziness and headache accompanied by recurrent weakness of his left arm. Imaging examinations demonstrated hydrocephalus and a cystic lesion around the cervical spinal cord. CSF test from lumbar puncture indicated chronic meningitis. MRI on 1 d after pseudomeningocele drainage showed a significant decrease in the cystic volume, suggesting that the cystic lesion would be subdural fluid collection rather than adhesive arachnoiditis. After dural defect repair, the patient's symptoms completely resolved and hydrocephalus gradually disappeared. CSF analysis at the 21-mo follow-up revealed significantly decreased protein level and WBC count. CONCLUSION: Subdural fluid collection rather than meningitis contributes to the hydrocephalus formation after cervical laminoplasty.
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OBJECTIVE: To explore the relationship among the serum D- two polymer, fibrinogen, C reactive protein and interleukin 6 and thrombus dissolution volume in acute iliac femoral venous thrombosis model rats. METHODS: A total of 60 rats were randomly divided into 3 groups: deep venous thrombosis group (DVT group), sham operation group and normal control group. In DVT group the single side of the iliofemoral vein incomplete with micro vessel was cliped under chloral hydrate anesthesia; in sham operation group the single side of the iliofemoral vein should be explored without using micro vessel clip under chloral hydrate anesthesia; the and normal control group only experienced chloral hydrate anesthesia. A positive correlation was showed between the 2 time points of D-dimer and the corresponding thrombolytic volume, and the Pearson coefficient was 0.307, and R2 was 0.412 (P<0.05). RESULTS: The D-dimer, fibrinogen, C reactive protein and interleukin-6 levels before and after treatment of 60 rats were shown to be significantly different (P<0.05) between DVT group, sham operation group and normal control group. The D-dimer and fibrinogen level was first rised and then decreased in DVT group, sham operation group. There was a positive correlation between C reactive protein/interleukin-6 and the level of D-dimer /fibrinogen from T1 to T3 time point (P<0.05). There was a negative correlation between C reactive protein/interleukin-6 and the level of D-dimer /fibrinogen from T4 to T6 time point (P<0.05). CONCLUSION: The changes of serum D-dimer, fibrinogen, C reactive protein and interleukin 6 in the acute iliac femoral vein thrombosis model firstly increase and then decrease. These changes can reflect the process of blood coagulation and fibrin dissolution in the course of venous thrombosis of iliac vein.
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Veia Femoral , Doença Aguda , Animais , Coagulação Sanguínea , Proteína C-Reativa , Produtos de Degradação da Fibrina e do Fibrinogênio , Fibrinogênio , Hemostáticos , Interleucina-6 , Ratos , Solubilidade , Trombose VenosaRESUMO
Tectorigenin (Tec) is an effective component of the traditional Chinese medicine Belamcanda chinensis, which has been reported to exert beneficial effects in various types of cancer. However, the activity and mechanism of Tec in osteosarcoma (OS) have not been investigated to date. The aim of the present study was to examine the inhibitory effect of Tec on OS and its underlying mechanism of action. OS cells (Saos2 and U2OS) were treated with various concentrations of Tec for 24, 48, and 72 h. Cell proliferation was evaluated using an CCK-8 assay. Cell migration and invasion ability were measured using the Transwell assay. The expressions of MMP1, MMP2, MMP9, and cleaved caspase3 were measured using real-time PCR and/or western blot analysis. We found that Tec inhibited the proliferation of OS cells (Saos2 and U2OS) in a dose-dependent and time-dependent manner. In addition, Tec significantly inhibited migration and invasion in OS cells (P<0.05). Tec upregulated the expression of cleaved caspase3, while downregulating the expression of MMP1, MMP2, and MMP9. Taken together, the present study provided fundamental evidence for the application of Tec in chemotherapy against OS.
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Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Isoflavonas/farmacologia , Metaloproteinases da Matriz/metabolismo , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Inibidores de Metaloproteinases de Matriz/farmacologia , Osteossarcoma/genética , Osteossarcoma/patologiaRESUMO
OBJECTIVE: This study was to explore the effects of RNA interference mediated vascular endothelial growth factor (VEGF) gene silencing on biological behavior of renal cell carcinoma (RCC), transplanted renal tumor and angiogenesis in nude mice. METHODS: The specific siRNA sequence targeting VEGF were designed and synthesized to construct hVEGF-siRNA plasmid which was transfected into RCC 786-O cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the detection of VEGF gene expression and western blot was adopted for the examination of VEGF protein expression. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell growth as well as cell migration and invasion. The transplanted renal tumor models in nude mice were established, and the growth condition of nude mice, and VEGF protein expression in transplanted tumor slices and the microvessel density (MVD) were detected. RESULTS: The expression level of VEGF mRNA in VEGF-siRNA group was significant lower than that in the control group and negative group, suggesting that establishment of plasmid specifically inhibited the expression of VEGF gene The expression level of VEGF protein in VEGF-siRNA group was significant lower than that in the control group and negative group. VEGF gene silencing has the significant inhibition effects on proliferation, migration and invasion of RCC 786-O cells. The tumor weight, VEGF protein positive rate and MVD in VEGF-siRNA group were significant lower than those in negative group and blank group. CONCLUSION: The VEGF gene silencing could inhibit the cell proliferation, migration and invasion of RCC 786-O cells; inhibition of VEGF protein expression could prevent transplanted RCC growth and tumor angiogenesis.
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Carcinoma de Células Renais/genética , Inativação Gênica , Neoplasias Renais/genética , Interferência de RNA , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Modelos Animais de Doenças , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Camundongos , Camundongos Nus , Neovascularização Patológica/genética , RNA Interferente Pequeno/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: We aimed to discover potential gene biomarkers for gastric cancer (GC) diagnosis. MATERIALS AND METHODS: Genechips of 10 GC tissues and 10 gastric mucosa (GM, para-carcinoma tissue, normal control) tissues were generated using an exon array of Affymetrix containing 30,000 genes. The differentially expressed genes (DEGs) between GC tissues and normal control were identified by the Limma package and analyzed by hierarchical clustering analysis. Gene ontology (GO) and pathway enrichment analyses were performed for investigating the functions of DEGs. Receiver operating characteristics (ROC) analysis was performed to measure the effects of biomarker candidates for diagnosis of GC. RESULTS: Totals of 896 up-regulated and 60 down-regulated DEGs were identified to be differentially expressed between GC samples and normal control. Hierarchical clustering analysis showed that DEGs were highly differentially expressed and most DEGs were up-regulated. The most significantly enriched GO-BP term was revealed to be mitotic cell cycle and the most significantly enriched pathway was cell cycle. The intersection analysis showed that most significant DEGs were cyclin B1 (CCNB1) and cyclin B2 (CCNB2). The sensitivities and specificities of CCNB1 and CCNB2 were both high (p<0.0001). Areas under the ROC curve for CCNB1 and CCNB2 were both greater than 0.9 (p<0.0001). CONCLUSIONS: CCNB1 and CCNB2, which were involved in cell cycle, played significant roles in the progression and development of GC and these genes may be potential biomarkers for diagnosis and prognosis of GC.
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Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/classificaçãoRESUMO
Spa2 is an important component of the multiprotein complex polarisome, which is involved in the establishment, maintenance, termination of polarized cell growth and is important for defining tip growth of filamentous fungi. In this study, we isolated an insertional mutant of the rice blast fungus Magnaporthe oryzae that formed smaller colony and conidia compared with the wild type. In the mutant, a spindle pole antigen gene MoSPA2 was disrupted by the integration of an exogenous plasmid. Targeted gene deletion and complementation assays demonstrated the gene disruption was responsible for the defects of the insertional mutant. Interestingly, the MoSpa2-GFP fusion protein was found to accumulate as a spot at hyphal tips, septa of hyphae and conidial tip cells where germ tubes are usually produced, but not in appressoria, infection hyphae or at the septa of conidia. Furthermore, the deletion mutants of MoSPA2 exhibited slower hyphal tip growth, more hyphal branches, and smaller size of conidial tip cells. However, MoSPA2 is not required for plant infection. These results indicate that MoSPA2 is required for vegetative hyphal growth and maintaining conidium morphology and that spotted accumulation of MoSpa2 is important for its functions during cell polar growth.