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OBJECTIVES: The aim of this study was to explore the relationship between the EAT-Lancet diet (ELD) and head and neck cancers (HNCs) in 101,755 Americans enrolled in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. STUDY DESIGN: Prospective cohort study. METHODS: ELD score was calculated to assess participant's adherence to ELD. Cox hazard regression models were utilised to evaluate the association of ELD and dietary components with HNC risk. Restricted cubic spline (RCS) plots were employed to explore the linearity of the relationships. Predefined subgroup analyses and sensitivity analyses were performed to identify potential effect modifiers and to assess the stability of the findings, respectively. RESULTS: After a mean follow-up of 8.84 years, 279 cases of HNCs, including 169 cases of oral cavity and pharyngeal cancers and 110 cases of laryngeal cancer were recorded. This study observed a dose-response negative correlation between ELD and HNCs (hazard ratio [HR]Q4 vs Q1: 0.52; 95% confidence interval [CI]: 0.34, 0.80; P-trend = 0.003; HRper SD increment: 0.80; 95% CI: 0.71, 0.91), and oral cavity and pharyngeal cancers (HRQ4 vs Q1: 0.52; 95% CI: 0.31, 0.88; P-trend = 0.008; HRper SD increment: 0.78; 95% CI: 0.66, 0.92). Analysis using RCS plots indicated a significant linear association between adherence to the ELD and reduced risk of HNCs and oral cavity and pharyngeal cancers (P-nonlinearity > 0.05). Subgroup analysis did not reveal significant interaction factors (P-interaction > 0.05), and sensitivity analysis confirmed the robustness of this study. Additionally, negative correlations were found between the consumption of fruits and whole grains and HNCs (fruits: HRQ4 vs Q1: 0.58; 95% CI: 0.40, 0.84; P-trend = 0.010; whole grains: HRQ4 vs Q1: 0.51; 95% CI: 0.26, 0.97; P-trend = 0.004). CONCLUSION: Adherence to ELD contributes to the prevention of HNCs.
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OBJECTIVE: To explore the therapeutic mechanism of compound Yuye Decoction against diabetic cardiomyopathy (DCM). METHODS: Drugbank, Gene Cards, OMIM and PharmGKb databases were used to obtain DCM-related targets, and the core targets were identified and functionally annotated by protein-protein interaction network analysis followed by GO and KEGG enrichment analysis. The "Traditional Chinese Medicine-Key Component-Key Target-Key Pathway" network was constructed using Cytoscape 3.9.1, and molecular docking was carried out for the key components and the core targets. In the animal experiment, Wistar rat models of DCM were treated with normal saline or Yuye Decoction by gavage at low (0.29 g/kg) and high (1.15 g/kg) doses for 8 weeks, and the changes in cardiac electrophysiology and histopathology were evaluated. The changes in serum levels of LDH, CK, and CK-MB were examined, and myocardial expressions of PI3K, P-PI3K, Akt, P-AKT, BAX, IL-6, and TNF-α were detected using Western blotting. RESULTS: We identified 61 active compounds in Yuye Decoction with 1057 targets, 3682 DCM-related disease targets, and 551 common targets between them. Enrichment of the core targets suggested that apoptosis, inflammation and the PI3K/Akt pathways were the key signaling pathways for DCM treatment. Molecular docking studies showed that the active components in Yuye Decoction including gold amidohydroxyethyl ester and kaempferol had strong binding activities with AKT1 and PIK3R1. In DCM rat models, treatment with Yuye Decoction significantly alleviated myocardial pathologies, reduced serum levels of LDH, CK and CK-MB, lowered myocardial expressions of BAX, IL-6 and TNF-α, and increased the expressions of P-PI3K and P-AKT. CONCLUSION: The therapeutic effect of compound Yuye Decoction against DCM is mediated by its multiple active components that act on multiple targets and pathways to inhibit cardiomyocyte apoptosis and inflammatory response by regulating the PI3K/Akt signaling pathway.
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Apoptose , Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Medicamentos de Ervas Chinesas , Inflamação , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Ratos Wistar , Transdução de Sinais , Animais , Ratos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Inflamação/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Masculino , Interleucina-6/metabolismoRESUMO
Echinococcosis poses a significant threat to public health. The Chinese government has implemented prevention and control measures to mitigate the impact of the disease. By analyzing data from the Chinese Center for Disease Control and Prevention and the State Council of the People's Republic of China, we found that implementation of these measures has reduced the infection rate by nearly 50% between 2004 to 2022 (from 0.3975 to 0.1944 per 100,000 person-years). Nonetheless, some regions still bear a significant disease burden, and lack of detailed information limites further evaluation of the effects on both alveolar and cystic echinococcosis. Our analysis supports the continuing implementation of these measures and suggests that enhanced wildlife management, case-based strategies, and surveillance systems will facilitate disease control.
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Equinococose , Humanos , Animais , Estudos Retrospectivos , China/epidemiologia , Equinococose/epidemiologia , Equinococose/prevenção & controle , Animais SelvagensRESUMO
OBJECTIVE: Network pharmacology is a bioinformatics-based research strategy for identifying the mechanisms of drugs and promoting drug development. This study used network pharmacology to investigate the mechanism of the Loulu-Cremastrae Pseudobulbus drug pair treating breast cancer (BC). MATERIALS AND METHODS: The ingredients and potential targets of the drug pair were searched with Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCSMP). National Center for Biotechnology Information (NCBI) and gene cards were used to search the targets of BC. Networks of "drugs-components-targets" and protein-protein interaction were constructed through Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out through common targets. Using AutoDock tool, molecular docking was performed to verify the binding between key targets and compounds. RESULTS: Finally, we selected 6 active compounds from the drug pair. A total of 61 targets were associated with the drug pair, and 15,295 targets were related to BC. 55 common targets were obtained after the intersection. The key targets included Transcription factor Jun (JUN), Heat shock protein HSP 90-alpha (HSP90AA1), and Caspase-3(CASP3). 327 terms were obtained by GO analysis. 78 pathways (p < 0.05) were identified through KEGG analysis. Molecular docking indicated that important compounds combined well with key targets. CONCLUSIONS: Various active compounds, including beta-sitosterol, 2-methoxy-9,10-dihydrophenanthrene-4,5-diol, and stigmasterol, can regulate multiple signaling pathways related to BC, such as the estrogen and prolactin signaling pathways, playing therapeutic roles in BC.
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Neoplasias , Farmacologia em Rede , Simulação de Acoplamento Molecular , Estrogênios , Biologia Computacional , Bases de Dados FactuaisRESUMO
Objective: To establish a patient-derived xenograft (PDX) humanized mouse model for hepatoblastoma in children. In addition, compare the biological consistency between successfully modeled PDX tumors and primary tumors in children while comparing and analyzing the influence of PDX model modeling success as a key factor. Methods: A PDX tumor model was constructed from fresh tumor tissue samples from 39 children with hepatoblastoma. The tumor growth time and volume size were recorded in detail. Simultaneously, 39 children's data were collected for experimental and clinical analysis. The difference in tumorigenesis rate between different parameters was analyzed by χ (2) test (categorical variable). Continuous variables with a normal distribution were compared using the t-test. Results: After cell passage and pathological diagnosis, 21 cases of hepatoblastoma PDX models were successfully constructed, with a success rate of 53.8% (21/39). Tumor samples from each generation of successfully modeled PDX models had pathology results that were consistent with those of the corresponding primary tumors. The analysis of the key factors affecting the tumor formation rate of PDX revealed that the metastasis rate was more successful in primary tumors than in liver in situ tumors (7/8 vs. 14/31, P = 0.049). However, there was no significant difference between tumor formation rates and pathological subtypes. According to the PDX tumor formation group comparison between the primary tumor and the metastatic tumor, there was no statistically significant difference between the two groups in terms of tumor formation time and tumor volume. Hematoxylin-eosin staining in hepatoblastoma's PDX mouse was consistent with the primary tumor. Immunohistochemistry positivity rates of four proteins, namely hepatocyte antigen (Hepatocyte), phosphatidylinositol glycan 3, ß-catenin, and alpha-fetoprotein, in primary tumor tissues and PDX mouse models were 100% vs. 100%, 100% vs. 95.24%, 100% vs. 100%, and 95.24% vs. 85.71%, respectively. Conclusion: A PDX mouse model for hepatoblastoma has been successfully established in children. The tumor formation rate is high, with metastatic tumors having a higher tumor formation rate than primary tumors and transplanted tumors retaining the biological characteristics of primary tumors.
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Hepatoblastoma , Neoplasias Hepáticas , Humanos , Criança , Animais , Camundongos , Xenoenxertos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVES: Dietary Approaches to Stop Hypertension (DASH) pattern has been found to aid in the reduction of obesity, oxidative stress, and chronic inflammation, which are all strongly linked to the development of head and neck cancer (HNC). Nevertheless, no epidemiological studies have investigated the association between this dietary pattern and HNC risk. This study was conducted with the purpose of bridging this gap in knowledge. DESIGN: A prospective cohort study involving 98,459 American adults aged 55 years and older. SETTING AND PARTICIPANTS: Data were drawn from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Trial. In the present study, participants with dependable energy intake data who furnished baseline and dietary history information were identified as the study population. METHODS: Diet was assessed by food frequency questionnaires and the DASH score was calculated to assess each participant's adherence to DASH eating pattern. Cox proportional hazards models were used to calculate multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the occurrence of HNC. To visualize the variation in cancer risk for HNC and its subtypes across the entire spectrum of DASH scores, restricted cubic spline plots were utilized. Additionally, a series of predefined subgroup analyses were performed to identify potential effect modifiers, and several sensitivity analyses were conducted to assess the stability of the findings. RESULTS: During a follow-up period of 871,879.6 person-years, 268 cases of HNC were identified, comprising 161 cases pertaining to oral cavity and pharynx cancers, as well as 96 cases of larynx cancer. In the fully adjusted model, adherence to the DASH diet was associated with a remarkable 57% reduction in the risk of HNC when comparing extreme quartiles (HR quartile 4 vs 1: 0.43; 95% CI: 0.28, 0.66; P for trend < 0.001). The restricted cubic spline plots demonstrated a linear dose-response relationship between the DASH score and the risk of HNC as well as its subtypes. Subgroup analysis revealed that the protective effect of the DASH diet against HNC was particularly pronounced in individuals with lower daily energy intake. The primary association remained robust in the sensitivity analysis. CONCLUSIONS: In American middle-aged and older population, adherence to the DASH diet may help prevent HNC, particularly for individuals with lower daily energy intake.
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Abordagens Dietéticas para Conter a Hipertensão , Neoplasias de Cabeça e Pescoço , Hipertensão , Masculino , Humanos , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Dieta , Neoplasias de Cabeça e Pescoço/prevenção & controle , Hipertensão/prevenção & controle , Fatores de RiscoRESUMO
Objective: To use metagenomic sequencing to compare the differences in intestinal microbiota species and metabolic pathways in patients with hepatitis B cirrhosis with or without ascites and further explore the correlation between the differential microbiota and clinical indicators and metabolic pathways. Methods: 20 hepatitis B cirrhosis cases [10 without ascites (HBLC-WOA), 10 with ascites (HBLC-WA), and 5 healthy controls (HC)] were selected from the previously studied 16S rRNA samples. Metagenome sequencing was performed on the intestinal microbiota samples. The Kruskal-Wallis rank sum test and Spearman test were used to identify and analyse differential intestinal microbiota populations, metabolic pathways, and their correlations. Results: (1) The overall structure of the intestinal microbiota differed significantly among the three groups (R = 0.19, P = 0.018). The HC group had the largest abundance of Firmicutes and the lowest abundance of Proteobacteria at the genus level. Firmicutes abundance was significantly decreased (P(fdr) < 0.01), while Proteobacteria abundance was significantly increased (P(fdr) < 0.01) in patients with cirrhosis accompanied by ascites; (2) LEfSe analysis revealed that 29 intestinal microbiota (18 in the HBLC-WA group and 11 in the HBLC-WOA group) played a significant role in the disease group. The unclassified Enterobacteriaceae and Klebsiella species in the HBLC-WA group and Enterobacteriaceae in the HBLC-WOA group were positively correlated with the Child-Turcotte-Pugh (CTP) score, prothrombin time, and international normalized ratio score and negatively correlated with albumin and hemoglobin levels (P < 0.05). Escherichia and Shigella in the HBLC-WA group were positively correlated with CTP scores (P < 0.05); (3) The correlation analysis results between the KEGG pathway and 29 specific intestinal microbiota revealed that Enterobacteriaceae and arachidonic acid, α-linolenic acid, glycerolipid metabolism, and fatty acid degradation were positively correlated in the lipid metabolism pathway, while most Enterobacteriaceae were positively correlated with branched-chain amino acid degradation and negatively correlated with aromatic amino acid biosynthesis in the amino acid metabolic pathway. Conclusion: A significant increment of Enterobacteriaceae in the intestines of HBLC-WA patients influenced hepatic reserve function and was associated with amino acid and lipid metabolic pathways. Therefore, attention should be paid to controlling the intestinal microbiota to prevent complications and improve the prognosis in patients with hepatitis B cirrhosis, especially in those with ascites.
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Microbioma Gastrointestinal , Hepatite B , Humanos , Ascite/complicações , RNA Ribossômico 16S/genética , Cirrose Hepática/complicações , Hepatite B/complicações , AminoácidosRESUMO
Objective: To investigate the value of qualitative and quantitative PET/MRI in the evaluation of axillary lymph node metastasis in patients with breast cancer. Methods: A total of 33 patients with breast cancer underwent preoperative PET/MRI examinations in Jingling Hospital from February to August in 2022 were retrospectively collected. All these patients were female, aged from 34 to 73 (51.4±11.3) years. Histopathological results and follow-up data were deemed as the referent standard, and the images were independently evaluated by two experienced breast imaging radiologists. The qualitative PET/MRI evaluation procedures were designed to evaluated the MRI alone to classify the axillary lymph nodes firstly, and then, the axillary lymph nodes status was reclassified by combining MRI and PET images. The net reclassification improvement index (NRI) was calculated using the R Programming Language (RStudio). The quantitative PET/MRI evaluation of the maximum standard uptake value (SUVmax) of axillary lymph nodes were measured by two radiologists, respectively, and the average value was compared with the referent standard to conduct a receiver operating characteristic (ROC) curve to select the optimal cutoff value of SUVmax. Based on the cutoff value and MRI classification results, axillary lymph nodes status was divided into quantitative PET/MRI positive or negative. The sensitivity, specificity and accuracy of MRI and quantitative PET/MRI in evaluating axillary lymph node metastasis were compared, and the area under the ROC curve (AUC) was compared. Results: There was no significant difference in sensitivity, specificity and accuracy between MRI and quantitative PET/MRI in evaluating lymph node metastasis of breast cancer (81.82% vs 95.46%; 81.82% vs 100%; 81.82% vs 96.97%) (all P>0.05). The AUC had a statistically significant difference [0.82 (0.65 to 0.93) vs 0.98 (0.85 to 1.00), P=0.026)]. According to the referent standard, in the 11 cases without ipsilateral axillary lymph node metastasis, the SUVmax was 0.83±0.18, while in the 22 cases with ipsilateral axillary lymph node metastasis, the SUVmax was [4.36 (1.77, 5.85)]. Compared with MRI alone, the NRI of qualitative PET/MRI in evaluating lymph node metastasis was 36.36% (P=0.021). Conclusion: Compared with MRI alone, quantitative PET/MRI has a higher AUC for evaluating axillary lymph node metastasis in patients with breast cancer, and qualitative PET/MRI had a better reclassification power in the evaluation of axillary lymph node metastasis.
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Neoplasias da Mama , Humanos , Feminino , Masculino , Metástase Linfática , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , LinfonodosRESUMO
Objective: To investigate the effect of different respiratory motion correction methods on PET images during chest PET/MRI scans. Methods: The data of 35 patients (24 males and 11 females, aged from 29 to 84 year) of pulmonary lesions with significantly high uptake in thoracic PET/MRI scan were retrospective collected from Jingling Hospital. Four different methods were used to reconstruct the PET data. Group A was the full-time 20 min without respiratory motion correction static acquisition (Static) as a control, group B was the end-expiration static collection (Q.Static), and group C was the multi-bins respiratory gating (Gated-Respiratory). In addition, the influence of the time being considered, group D was added for reconstruction in the first 1/3 period (6 min 40 s) of group A. Then, the maximum value (L-SUVmax) and the mean value (L-SUVmean) of the SUV of the lesion, the mean value (B-SUVmean) and the standard deviation (B-SUVsd) of the SUV of the background under each reconstruction results were measured, and for each lesion the signal-to-noise ratio (L-SNR) was calculated. In order to exclude the interference of the background, the mean of the relative SUV (L-dSUVmean) of the L-SUVmean relative to the B-SUVmean was also calculated. Finally, One-Way Repeated Measures ANOVA was used, and the post-hoc pairwise comparison between groups was tested by Bonferroni's modified test. Results: There was statistically significant difference among group B or group C compared to group A and group D in L-SUVmax, L-SUVmean and L-dSUVmean [L-SUVmax:group B vs group A or group D was 8.06±3.57 vs 7.73±3.45 or 7.61±3.50, group C vs group A or group D was 8.04±3.56 vs 7.73±3.45 or 7.61±3.50 (all P<0.05); L-SUVmean: group B vs group A or group D was 4.12±1.78 vs 3.98±1.72 or 3.91±1.71, group C vs group A or group D was 4.13±1.78 vs 3.98±1.72 or 3.91±1.71 (all P<0.05); L-dSUVmean: group B vs group A or group D was 3.52±0.16 vs 3.39±0.18 or 3.31±0.18, group C vs group A or group D was 3.53±0.18 vs 3.39±0.18 or 3.31±0.18 (all P<0.05)], but there was no statistically significant difference between group B and group C (all P>0.05). There were statistically significant differences between group D and group A in B-SUVsd (0.07±0.00 vs 0.07±0.00, P=0.023) and L-SNR (69.80±44.57 vs 85.35±68.98, P=0.001). There was no statistically significant difference between group D and group A in L-SUVmax, L-SUVmean, B-SUVmean and L-dSUVmean (all P>0.05). Conclusions: There was no significant difference in PET image quality between the Q.static and Gated-Respiratory group, both of the two groups were better than the Static group which with no Gated-Respiratory motion correction. If non-respiratory gated Static is used, the PET acquisition time is recommended to be 6 min 40 s.
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Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Feminino , Masculino , Humanos , Estudos Retrospectivos , Radiografia , TóraxRESUMO
Objective: To compare the point-of-care assays for tear matrix metalloproteinase 9 (MMP-9) using domestic and InflammaDry kits, and to evaluate the feasibility of diagnosing dry eye with the domestic kit. Methods: It was a cross-sectional study. Thirty dry eye patients and 30 age-and sex-matched normal volunteers were continuously enrolled in this cross-sectional study from June 2022 to July 2022. Both domestic and InflammaDry kits were used to detect the tear MMP-9 levels. The positive rates were recorded for qualitative analysis, and the gray ratios of bands (the gray value of detection bands to that of control bands) were collected for quantitative analysis. The correlations of MMP-9 levels with age, ocular surface disease index, fluorescence tear break-up time, tear meniscus height, Schirmer's â test score, corneal fluorescein staining score, and meibomian gland dropout were analyzed. The Mann-Whitney U test, paired Chi-square test, Kappa test, and Spearman's correlation coefficient were used for statistical analysis. Results: There were 14 males and 16 females (30 eyes) in the control group, and their age was (39.37±19.55) years. In the dry eye group, 11 males and 19 females (30 eyes), aged (46.87±17.85) years, had moderate to severe dry eye. The positive rates of MMP-9 in tear fluid were significantly different between dry eye patients (InflammaDry: 86.67%; domestic kit: 70.00%) and controls (InflammaDry: 16.67%, P<0.001; domestic kit: 6.67%, P<0.001). Although the sensitivity of the domestic kit was lower than that of the InflammaDry kit (70.0% vs. 86.7%, P=0.001), the specificity was higher (93.3% vs. 83.3%, P=0.001). In dry eye patients, the positive coincidence rate was 80.7% (21/26), the negative coincidence rate was 100% (4/4), and the total coincidence rate was 83.3% (25/30), with no significant difference between the two kits (McNemar test: χ2=3.20, P>0.05), and the results of both kits were consistent (Kappa=0.53, P=0.001). The Spearman's correlation coefficient showed the gray ratios using both kits were positively correlated with the corneal fluorescein staining score (InflammaDry: ρ=0.48, P<0.05; domestic kit: ρ=0.52, P=0.003). Conclusion: The performances of the domestic and InflammaDry kits are consistent in the point-of-care assay for tear MMP-9, and the domestic kit has lower sensitivity but higher specificity.
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Síndromes do Olho Seco , Metaloproteinase 9 da Matriz , Feminino , Humanos , Masculino , Estudos Transversais , Síndromes do Olho Seco/diagnóstico , Fluoresceína , Metaloproteinase 9 da Matriz/análise , Glândulas Tarsais , Sistemas Automatizados de Assistência Junto ao Leito , Lágrimas/química , Adulto Jovem , Adulto , Pessoa de Meia-IdadeRESUMO
Objective: To explore whether hsa_circ_0000670 promotes the progression of gastric cancer by regulating the miR-515-5p/SIX1 molecular axis. Methods: The gastric cancer and adjacent normal tissues of 35 gastric cancer patients admitted to Rugao Hospital Affiliated to Nantong University from 2014 to 2015 were collected. The expression levels of circ_0000670, miR-515-5p and Sine oculis homeobox 1 (SIX1) in gastric cancer tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The correlations between circ_0000670 and miR-515-5p, miR-515-5p and SIX1, circ_0000670 and SIX1 were analyzed by the Pearson method. Patients were divided into low circ_0000670 expression group (17 cases) and high circ_0000670 expression group (18 cases) based on the median of circ_0000670 expression level, and Kaplan-Meier was used to analyze the 5-year survival of patients. Cell proliferation was assessed via clone formation assay. Cell cycle and apoptosis were detected by flow cytometry. Wound healing and Transwell assays were used to detect cell migration and invasion ability. The targeting relationship between miR-515-5p and circ_0000670 or SIX1 was confirmed by the dual luciferase reporter assay. Nude mice were injected into HGC-27 cells transfected with sh-NC or sh-circ_0000670, and the volume and weight of the transplanted tumor were measured, also, the levels of circ_0000670, miR-515-5p and SIX1 in the transplanted tumor tissue were detected. Results: The expression levels of circ_0000670 and SIX1 in gastric cancer tissues and cell lines were significantly increased (P<0.05), while the expression levels of miR-515-5p were significantly decreased (P<0.05). The survival rate of patients in the low circ_0000670 expression group (82.4%) was significantly higher than that in the high circ_0000670 expression group (28.7%, P=0.034). Circ_0000670 was negatively correlated with miR-515-5p (r=-0.846, P<0.001), and miR-515-5p was negatively correlated with SIX1 (r=-0.615, P<0.001), but circ_0000670 was positively correlated with SIX1 (r=0.814, P<0.001). Transfection of si-circ_0000670 or miR-515-5p mimic could significantly reduce the number of clone-forming cells, migration distance, migration and invasion cells (P<0.05), and increase the ratio of G(0)/G(1) phase cells, apoptosis rate and the protein level of E-cadherin (P<0.05), decreased the proportion of S-phase cells and the protein level of Vimentin (P<0.05). The dual luciferase report assay confirmed that circ_0000670 could target miR-515-5p, and miR-515-5p could bind to SIX1. Co-transfection of si-circ_0000670 and miR-515-5p inhibitor could significantly attenuate the effects of si-circ_0000670 on cell proliferation, migration, invasion, cell cycle and apoptosis (P<0.05). Co-transfection of miR-515-5p mimic and pcDNA-SIX1 could significantly reduce the effects of miR-515-5p mimic on cell proliferation, migration, invasion, cell cycle and apoptosis (P<0.05). Compared with the sh-NC group [volume=(596.20±125.46) mm(3) and weight=(538.00±114.39) g], the volume and weight of transplanted tumors in the sh-circ_0000670 group [volume=(299.20±47.58) mm 3 and weight=(289.80±48.73 g)] were significantly reduced (P<0.05), the expression levels of circ_0000670 and SIX1 were significantly reduced (P<0.05), and the expression level of miR-515-5p was significantly increased (P<0.05). Conclusion: Knockdown of circ_0000670 could inhibit cell proliferation, migration, invasion of gastric cancer cells, induce cell cycle arrest in G(0)/G(1) phase and promote cell apoptosis by regulating the miR-515-5p/SIX1 axis.
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MicroRNAs , Neoplasias Gástricas , Animais , Camundongos , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Camundongos Nus , MicroRNAs/genética , Neoplasias Gástricas/genéticaRESUMO
Objective: To examine the association of body mass index (BMI) and waist circumference (WC) with frailty among oldest-old adults in China. Methods: A total of 7 987 people aged 80 years and older (oldest-old) who participated in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2017-2018 were included. Information on demographic characteristics, behavior pattern, diet, activities of daily living, cognitive function, health status, disease condition were collected by questionnaire and physical examination. Generalized linear mixed model and restricted cubic splines (RCS) were used to analyze the association of BMI and WC with frailty. Results: The mean age of all participants was 91.7 years, and their mean BMI and WC were (21.3±3.5) kg/m2 and (82.9±10.5) cm, respectively. The proportion of male was 42.3% (3 377/7 987), and the proportion of people with frailty was 33.7% (2 664/7 987). After controlling confounding factors, compared with T2 (19.1-22.1 kg/m2) of BMI, the OR (95%CI) of the female T1 (<19.1 kg/m2) and T3 (≥22.2 kg/m2) group was 1.39 (1.17-1.65) and 1.27 (1.07-1.52), respectively. Compared with T2 (77-85 cm) of WC, the OR (95%CI) of female T1 (<77 cm) and T3 (≥86 cm) group was 1.20 (1.01-1.42) and 1.10 (0.93-1.31), respectively. The results of multiple linear regression model with restrictive cubic spline showed that there was a non-linear association of BMI and WC with frailty in female. Conclusion: There is a U-shaped association of BMI and WC with frailty in female participants.
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Fragilidade , Adulto , Masculino , Feminino , Humanos , Idoso de 80 Anos ou mais , Circunferência da Cintura , Índice de Massa Corporal , Fragilidade/epidemiologia , Atividades Cotidianas , China/epidemiologia , Fatores de RiscoRESUMO
OBJECTIVE: Stomach adenocarcinoma (STAD) is the major cancer worldwide with high morbidity and mortality rate. Late diagnosis and limited treatment options of STAD lead to disease progression, spread, and metastasis. Therefore, finding a new biomarker to diagnosis and treatment is very important for STAD in clinical practice. MATERIALS AND METHODS: The clinical data, transcriptome data and CCLE data were downloaded from TCGA database and CCLE database, respectively. TIMER website, TISIDB website and CIBERSORT methodology were used to analyse immune infiltration. R software and R package were used to analyse gene difference expression, determine co-expression genes, conduct gene enrichment analyses, construct a prognostic signature and establish nomogram. RESULTS: MASP1 was decreased in STAD compared with normal tissue at the mRNA level (p < 0.001). The enrichment analysis showed that mismatch repair (MMR) was related to the MASP1 gene. Up-regulation of MAPS1 expression was positively associated with dendritic cells (p < 0.01), neutrophils (p < 0.05), macrophages (p < 0.001), CD4+ T cells (p < 0.001) and B cells (p < 0.05). A four-gene prognostic signature was determined based on MASP1-related immunomodulators. The prognostic signature was an independent prognostic predictor in STAD. Finally, we established a nomogram to forecast survival and the nomogram has a good prediction accuracy. CONCLUSIONS: In STAD, MASP1 is closely related to immunity. MASP1 has the potential to positively regulate the abundance of immune cells. The MASP1-related prognosis signature and nomogram can accurately predict the survival of patients with STAD. Therefore, MASP1 is likely to be a diagnosis and promising immunotherapy target spot in STAD clinical practice.
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Adenocarcinoma , Serina Proteases Associadas a Proteína de Ligação a Manose , Neoplasias Gástricas , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Humanos , Serina Proteases Associadas a Proteína de Ligação a Manose/genética , Serina Proteases Associadas a Proteína de Ligação a Manose/metabolismo , Prognóstico , RNA Mensageiro/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismoRESUMO
OBJECTIVE: Our review aims at comparing the morbidity and mortality-related risks associated with the pre-injury administration of VK-antagonists or DOACs in elderly patients with TBI. MATERIALS AND METHODS: We performed a systematic search of the academic literature across five databases (Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE), following PRISMA guidelines. We conducted a random-effect meta-analysis to compare the influence of pre-injury VK-antagonists or DOACs administration on the overall intensive care unit and hospital stays of patients with TBI. We also evaluated the overall risks associated with VK-antagonists and with DOACs for intracranial hemorrhage progression, surgical intervention, and overall mortality in patients with TBI. RESULTS: From 973 studies, we found 11 eligible with 4,991 patients with traumatic brain injury (mean age, 77.82 ± 6.76 years). Our meta-analysis revealed insignificantly higher odds of surgical intervention (OR=1.72) and mortality (OR=1.07) associated with VK-antagonists administration than with DOACs administration. Similarly, we found that the intensive care unit (Hedge's g, 0.13) and hospital (g, 0.26) stays were insignificantly longer for individuals on VK-antagonists than for those on DOAC. Moreover, we observed insignificantly higher intracranial hemorrhage progression risks (OR=1.22) for individuals receiving DOACs than for those receiving VK-antagonists. CONCLUSIONS: This study provides evidence on the morbidity and mortality-related outcomes associated with the pre-injury administration of VK-antagonists or DOACs in patients with TBI. We found no significant differences between VK-antagonists and DOACs on the overall morbidity (hospital and intensive care unit stays, intracranial hemorrhage, and surgical intervention frequency) and mortality outcomes in elderly patients with TBI.
Assuntos
Anticoagulantes , Lesões Encefálicas Traumáticas , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Fibrinolíticos/efeitos adversos , Humanos , Hemorragias Intracranianas , Tempo de InternaçãoRESUMO
Objective: To explore the impact of composite clinical worsening (cCW) events and its components on the prognosis of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH). Methods: This is a retrospective study. Patients who were diagnosed with CHD-PAH in Beijing Anzhen Hospital between January 2007 and July 2018, were included, and their baseline clinical data including demographic, clinical manifestations and New York Heart Association (NYHA) classification were collected retrospectively. All-cause deaths and clinical worsening events were recorded, which included syncope, PAH related hospitalization, NYHA classification deterioration and ≥ 2 PAH related clinical symptoms (dyspnea, hemoptysis, edema, chest pain, palpitations, cyanosis) appearance/progress. Three kinds of cCW events were defined: cCW1 (included PAH related hospitalization, NYHA classification deterioration), cCW2 (increased syncope on the basis of cCW1) and cCW3 (increased ≥ 2 PAH related clinical symptoms appearance/progress on the basis of cCW2). The Kaplan-Meier survival curve was used to analyze the long-term survival of the included patients. Univariate and multivariate Cox regression models were used to evaluate the impact of cCW events and their components on the risk of all-cause mortality. Results: A total of 525 patients with CHD-PAH were included in this study. The median age at diagnosis was 20.7 (11.2, 30.3) years. There were 43.8% children (<18 years), and 68.8% female patients. There were 431 patients (82.1%) with NYHA classification II. A total of 180 patients had PAH symptoms at diagnosis. The median follow-up time was 4.5 (2.6, 6.7) years. Forty-seven patients (9.0%) died during the follow-up period. Survival rates at 1, 5 and 10 years after diagnosis of PAH were 98.0%, 89.9% and 84.4%, respectively. Cox multivariate analysis showed that NYHA classification deterioration (HR=3.901, 95%CI 1.863-8.169, P<0.001), ≥2 PAH symptoms appearance/progress (HR=4.458, 95%CI 1.870-10.625, P<0.001), PAH-related hospitalization (HR=4.058, 95%CI 1.851-8.896, P<0.001) and syncope (HR=11.313, 95%CI 4.860-26.332, P<0.001) were independent predictors of increased risk of death. All 3 kinds of cCW events were significantly associated with the significantly increased risk of death, and cCW2 was highly predictive to increased risk of death (HR=15.476, 95%CI 4.346-37.576, P<0.001). Conclusions: The overall long-term prognosis of CHD-PAH patients in this study is relatively good. cCW events and its components (NYHA classification deterioration, ≥2 PAH symptoms occurrence/worsening, PAH-related hospitalization and syncope) have adverse influence on all-cause death in this patient cohort.
Assuntos
Cardiopatias Congênitas , Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Criança , Hipertensão Pulmonar Primária Familiar/complicações , Feminino , Cardiopatias Congênitas/complicações , Humanos , Hipertensão Pulmonar/complicações , Masculino , Estudos RetrospectivosRESUMO
The aim of this study was to analyse the impact of postoperative positron emission tomography-computed tomography (PET-CT) before adjuvant treatment in oral squamous cell carcinoma (OSCC) patients. Patients with OSCC requiring adjuvant treatment following surgery were divided retrospectively into two groups based on the implementation of PET-CT. The study endpoints were disease-specific survival (DSS) and overall survival (OS). A total of 123 patients underwent PET-CT examination; 28 had abnormal images, but only seven were confirmed to be pathologically positive. A total of 145 patients underwent computed tomography/magnetic resonance imaging (CT/MRI) examination; 20 had abnormal images, but only one was confirmed to be pathologically positive. The median OS time was 5.4 years in the PET-CT group and 4.3 years in the CT/MRI group, demonstrating a significant difference (P = 0.024). Findings were similar for the median DSS time. In patients with positive PET-CT results, the median DSS was 4.3 years and median OS was 3.5 years, and in those with negative PET-CT results, the median survival time could not be calculated as fewer than 50% of patients reached these endpoints; both differences were significant (P = 0.007 and P < 0.001). Although the false-positive rate of postoperative PET-CT is high, it improves the chance of survival through early and more frequent detection of recurrence.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/terapia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Radioterapia Adjuvante , Estudos Retrospectivos , Quimiorradioterapia , Fluordesoxiglucose F18 , Tomografia por Emissão de PósitronsRESUMO
Objective: To observe the effects of estradiol on expression of plasma membrane Ca2+-ATPase isoform 2 in inner ear of rats. Methods: Twenty-five Three-months-old female Sprague-Dawley rats were randomly and equally divided into five groups by random number table mathod,with five rats in each group. Animals in Sham group were sham-operated while others were bilateral ovariactmized. One month after modeling, the OVX groups were supplemented with estradiol (E2 group), progesterone (P group), estradiol and progesterone (E2+P group)and vehicle sesame oil (Veh group), while the Sham operation group (Sham group) was supplemented with vehicle sesame oil.All rats were sacrificed and otocysts were obtained immediately. Enzyme-linked immunosorbent assay was used to detect the changes in serum estradiol and progesterone levels of each group of rats before operation, before treatment and before sacrifice. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of total PMCA2 protein and mRNA in the inner ear of each group. Results: There was no significant difference in serum estradiol and progesterone levels among the five groups before operated(P>0.05). Before treatment, the serum estradiol and progesterone levels of rats in each group were significantly lower than those in Sham group (P<0.05). The serum estradiol level in E2 group and E2+P group was not significantly different from that in Sham group (P>0.05), while the serum estradiol level in P group and Veh group was significantly different from that in Sham group (P<0.05). The level of progesterone in P group and E2+P group was higher than that in Sham group (P<0.05), while the level of progesterone in Veh group and E2 group was lower than that in Sham group (P<0.05). Protein and mRNA expression of PMCA2 in P and Veh groups were significantly decreased compared with that of Sham group (P<0.05) while the expression levels underwent no significantly change in E2 and E2+P groups (P<0.05). Conclusion: The decrease of serum estradiol level can reduce the expression of otolith regulatory protein PMCA2 in rats, and then affect otolith metabolism, which may be an important link of estrogen affecting otolith metabolism.
Assuntos
Orelha Interna , Estradiol , Animais , Feminino , Ratos , Adenosina Trifosfatases , Orelha Interna/metabolismo , Estradiol/farmacologia , Progesterona/farmacologia , Isoformas de Proteínas , Ratos Sprague-Dawley , RNA Mensageiro/metabolismo , Óleo de GergelimRESUMO
The feasibility of submandibular gland (SMG) preservation during neck dissection has been described. The aim of this study was to analyse the functional outcomes in patients undergoing SMG preservation during neck dissection for cT1-2N0 oral squamous cell carcinoma. Consecutive patients were divided into two groups based on the management of the SMG, and underwent a saliva flow test before surgery, 7 days after surgery, and at 3, 6, 9, and 12 months after surgery. All enrolled patients completed the fourth version of the University of Washington Quality of Life (UWQOL) questionnaire at 12 months after surgery. In patients who underwent SMG preservation during neck dissection, the flow rate at 7 days after surgery was significantly lower than that preoperative; however, it gradually returned to baseline at 9 months after surgery. The saliva flow rate at 9 months after surgery was similar to that at 12 months after surgery. Further, patients with SMG preservation had higher scores for the activity, swallowing, chewing, and saliva domains than patients without SMG preservation. The results of the study suggest that saliva secretion ability can be preserved following SMG-sparing neck dissection, and that SMG preservation improves postoperative quality of life.