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AIM: To develop a simple and convenient method based on multiparametric magnetic resonance imaging (MRI) and clinical features to non-invasively predict tumour-infiltrating lymphocytes (TILs) in breast cancer (BC) and to explore the relationship between TIL levels and disease-free survival (DFS). MATERIALS AND METHODS: A total of 172 BC patients were enrolled between November 2017 and June 2021 in this retrospective study. The patients were divided into high (≥10%) and low (<10%) TIL groups. Clinicopathological data were collected. MRI features were reviewed by two radiologists. Predictors associated with TILs were determined by using multivariable logistic regression analyses. Kaplan-Meier survival curves based on TIL levels were used to estimate DFS. RESULTS: A total of 102 patients with low TILs and 70 patients with high TILs were included in the study. Tumour size (odds ratio [OR], 1.040; 95% confidence interval [CI]: 1.006, 1.075; p=0.020), apparent diffusion coefficient (ADC; OR, 1.003; 95% CI: 1.001, 1.005; p=0.015), clinical axillary lymph node status (CALNS; OR, 3.222; 95% CI: 1.372,7.568; p=0.007), and enhancement pattern (OR, 0.284; 95% CI: 0.143, 0.563; p<0.001) were independently associated with TIL levels. These features were used in the ALSE model (where A is ADC, L is CALNS, S is size, and E is enhancement pattern). High TILs were associated with better DFS (p=0.016). CONCLUSION: The ALSE model derived from multiparametric MRI and clinical features could non-invasively predict TIL levels in BC, and high TILs were associated with longer DFS, especially in human epidermal growth factor receptor 2 (HER2)-positive BC and triple-negative BC (TNBC).
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Neoplasias da Mama , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/metabolismo , Estudos Retrospectivos , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Intervalo Livre de Doença , PrognósticoRESUMO
AIM: To develop an integrated model based on preoperative magnetic resonance imaging (MRI) features for predicting early recurrence in patients with triple-negative breast cancer (TNBC). MATERIALS AND METHODS: Women with TNBC who underwent breast MRI and surgery between 2009 and 2019 were evaluated retrospectively. Two breast radiologists reviewed MRI images independently based on the Breast Imaging Reporting and Data System Lexicon (BI-RADS), and classified the breast oedema scores on T2-weighted imaging (WI) as no oedema, peritumoural oedema, prepectoral oedema, or subcutaneous oedema. The relationship between disease-free survival (DFS) and MRI features was analysed by Cox regression, and a nomogram model was generated based on the results. RESULTS: 150 patients with TNBC were included and divided into a training cohort (n=78) and validation cohort (n=72). MRI features including subcutaneous oedema and rim enhancement showed a tendency to worsen DFS in univariate analysis. Multivariate analysis showed that subcutaneous oedema (p=0.049, HR [95% confidence interval {CI} = 8.24 [1.01-67.52]) and rim enhancement (p=0.016, HR [95% CI] = 4.38 [1.32-14.54]) were independent predictors for DFS. In the nomogram, the areas under the curves (AUCs) of the training cohort was 0.808, and that of the validation cohort was 0.875. CONCLUSION: The presence of subcutaneous oedema or rim enhancement on preoperative breast MRI was shown to be a good predictor of poor survival outcomes in patients with TNBC.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Mama , Edema/diagnóstico por imagemRESUMO
In order to explore the mechanism of gefitinib-acquired resistance in lung cancer, a new biomarker has been developed for early clinical diagnosis and intervention; human NSCLC (Non-Small Cell Lung Cancer) cell lines H292 (denoted as H292S) and PC9 (denoted as PC9S) were used to establish gefitinibresistant NSCLC cell lines H292 and PC9 models. CCK-8 (Cell Counting Kit-8) method was used to test the drug resistance of the cells. circRNAs (circular RNAs) that were differentially expressed before and after resistance were screened by RNA sequencing technology. The effects of circSETD3 overexpression and interference on the sensitivity of gefitinib was observed to analyze the nuclear localization of circSETD3 and verify the interaction between circSETD3-miR-520h-ABCG2. The results showed that the most significant change in differential expression of human NSCLC cell lines before and after drug resistance was hsa_circ_0000567, that is, circSETD3, which is mainly present in the cytoplasm. In H292S and PC9S, compared with the negative control group, the cell proliferation ability of the overexpression group was significantly increased, and the apoptosis ability was significantly decreased. In H292R and PC9R, compared with the negative control group, the proliferation ability of the interference group was significantly decreased, and the apoptosis ability was significantly increased. Overexpression of circSETD3 to H292S and PC9S, the expression of ABCG2 increased significantly. Also, the expression of ABCG2 decreased significantly after transfection with miR-520h mimics. H292R and PC9R interfered with circSETD3, the expression of ABCG2 decreased significantly. Moreover, the expression of ABCG2 increased significantly after transfection with miR-520h inhibitor. In conclusion, circSETD3 can be used as a novel biomarker for lung cancer. It relieves miR-520h degradation of the transporter ABCG2 by down-regulating the miR-520h expression, causing gefitinib to be pumped out of the cell.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Pulmonares/genética , MicroRNAs/genética , Músculo Liso Vascular , RNA Circular , Transdução de SinaisRESUMO
AIM: To assess the performance of the apparent diffusion coefficient (ADC) and relative ADC (rADC) to differentiate benign from malignant breast lesions using the plateau pattern of the time-intensity curve (Type II TIC), including the impact of lesions-enhancement subtypes and menopausal status of patients. MATERIALS AND METHODS: Between September 2016 and December 2019, 408 patients with 169 benign and 239 malignant lesions with Type II TIC underwent magnetic resonance imaging (MRI), including diffusion-weighted imaging, with b-values of 50 and 800 s/mm2. ADC and rADC values were calculated by placing regions of interest (ROIs) on the lesion, the parenchyma of the normal breast, and the pectoralis major muscle. A receiver operating characteristic (ROC) curve was generated to compare the diagnostic performance of each parameter in distinguishing between benign and malignant breast lesions. Further classification was undertaken to study the discriminatory performance of each parameter in the different lesions enhancement subtypes (mass-like enhancement [MLE] and non-MLE [NMLE]) and menopausal status of patients (pre-menopausal and post-menopausal). RESULTS: There was a significant difference in the ADC and rADC values between benign and malignant lesions. The sensitivities of lesion ADC, gland rADC, and muscle rADC were 79.29%, 77.51%, and 79.29%, respectively, with specificities of 94.56%, 82.01%, and 94.98%, respectively. The area under the ROC curve (AUC) of muscle rADC was the highest (AUC=0.92), especially in the MLE subtype (AUC=0.96), and was not affected by the menopausal status. CONCLUSION: Muscle rADC and lesion ADC assessment improved the diagnostic performance of breast MRI in distinguishing between benign and malignant breast lesions with Type II TIC, especially muscle rADC in the MLE subtype.
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Neoplasias da Mama/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Mama/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , TempoRESUMO
BACKGROUND: The rampant spread of the novel coronavirus disease (COVID-19) has assumed pandemic proportions across the world. Attempts to contain its spread have entailed varying early screening and triage strategies implemented in different countries and regions. AIM: To share the experience of scientific and standardized management of fever clinics in China, which provide the first effective checkpoint for the prevention and control of COVID-19. INTRODUCTION: A fever clinic was established at our hospital in Tianjin, China, for initially identifying suspected cases of COVID-19 and controlling the spread of the disease. METHODS: The management system covered the following aspects: spatial layout; partitioning of functional zones; a work management system and associated processes; management of personnel, materials and equipment; and patient education. RESULTS: Within two months of introducing these measures, there was a comprehensive reduction in the number of new COVID-19 cases in Tianjin, and zero infections occurred among medical staff at the fever clinic. DISCUSSION: The fever clinic plays an important role in the early detection, isolation and referral of patients presenting with fevers of unknown origin. Broad screening criteria, an adequate warning mechanism, manpower reserves and staff training at the clinic are essential for the early management of epidemics. CONCLUSION: The spread of COVID-19 has been effectively curbed through the establishment of the fever clinic, which merits widespread promotion and application. IMPLICATIONS FOR NURSING AND HEALTH POLICIES: Health managers should be made aware of the important role of fever clinics in the early detection, isolation and referral of patients, and in the treatment of infectious diseases to prevent and control their spread. In the early stage of an epidemic, fever clinics should be established in key areas with concentrated clusters of cases. Simultaneously, the health and safety of health professionals require attention.
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Instituições de Assistência Ambulatorial/organização & administração , COVID-19/enfermagem , Febre de Causa Desconhecida/enfermagem , Pneumonia Viral/enfermagem , COVID-19/epidemiologia , China/epidemiologia , Arquitetura de Instituições de Saúde , Febre de Causa Desconhecida/epidemiologia , Febre de Causa Desconhecida/virologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , SARS-CoV-2RESUMO
Objective: The purpose of this study was to investigate the effects of CYP2C19 gene mutations on clopidogrel antiplatelet activity in the patients with coronary heart disease treated by percutaneous coronary intervention. Methods: Patients with coronary heart disease, who hospitalized in the Second Affiliated Hospital of Nanchang University from March 2011 to June 2019, and healthy individuals with matching genetic background, gender, and age as controls were included in this study. Basic clinical data were analyzed and blood samples of all research subjects were obtained for extraction of DNA, and Sanger first-generation sequencing method was used to detect CYP2C19 gene mutation from full exon and exon and intron junction. CYP2C19 gene variations in patients with coronary heart disease were compared with the 1000 Genomes Browse database and the sequencing results of healthy controls to determine whether the gene variation was a genetic mutation or a genetic polymorphism. After that, PolyPhen-2 prediction software was used to analyze the harmfulness of gene mutations to predict the effect of mutations on protein function. The same dose of CYP2C19 wild-type plasmid and the CYP2C19 gene mutant plasmids were transfected into human normal liver cells HL-7702. After transfection of 24 h, the expression of CYP2C19 protease in each group was detected. The liver S9 protein was incubated with clopidogrel, acted on platelets to detect the platelet aggregation rate and the activity of human vasodilator-activated phosphoprotein (VASP). Results: A total of 1 493 patients with coronary heart disease (59.36%) were enrolled, the average age was (64.5±10.4) years old, of which 1 129 were male (75.62%). Meanwhile, 1 022 healthy physical examination volunteers (40.64%) were enrolled, and the average age was (64.1±11.0) years old, of which 778 were male (76.13%). A total of 5 gene mutations of CYP2C19 gene were identified in 12 patients (0.80%), namely, 4 known mutations T130K (1 case), M136K (6 cases), N277K (3 cases), V472I (1 case) and one new mutation G27V (1 case), no corresponding gene mutation was found in healthy controls. It was found that T130K and M136K were probably damaging, G27V was possibly damaging, and N277K and V472I were benign mutations. In vitro, we demonstrated that the platelet aggregation rate of the M136K gene mutation group was 24.83% lower than that of the wild type (59.58% vs. 34.75%; P<0.05), and the phosphorylated VASP level was 23.0% higher than that of the wild type (1.0 vs. 1.23; P<0.05). However, the platelet aggregation rate and phosphorylated VASP level were similar between of G27V, T130K, N277K, V472I gene mutation groups and wild type group (P>0.05). Conclusions: In this study, 5 gene mutations are defined in patients with coronary heart disease, namely G27V, T130K, M136K, N277K, V472I. In vitro functional studies show that CYP2C19 gene mutation M136K, as a gain-of-function gene mutation, can enhance the activation of CYP2C19 enzyme on clopidogrel, thereby inhibiting the platelet aggregation rate.
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OBJECTIVES: This study determined the rate of secondary infection among contacts of individuals with confirmed coronavirus disease 2019 (COVID-19) in Hangzhou according to the type of contacts, the intensity of contacts, and their relationship with the index patient. STUDY DESIGN: This is a retrospective cohort study. METHODS: The analysis used the data of 2994 contacts of 144 individuals with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The contacts were categorized according to the information source, type of contact, location, intensity of contact, and relationship with the index patient. RESULTS: The incidence of infection differed significantly according to contact type. Of the contacts, 186 (6.2%) developed symptoms, and 71 (2.4%) had confirmed SARS-CoV-2 infection. The main symptoms were cough and fever. Compared with those who had brief contact with the index case, those who had dined with the index case had 2.6 times higher risk of acquiring infection; those who had shared transport with, had visited, or had contact with the index case in a medical institution had 3.6 times higher risk of acquiring infection; and household contacts had 41.7 times higher risk of acquiring infection. Family members had 31.6 times higher risk of acquiring infection than healthcare providers or other patients exposed to an index case. CONCLUSIONS: The form and frequency of contact are the main factors affecting the risk of infection among contacts of individuals with COVID-19. Centralized isolation and observation of close contacts of individuals with confirmed SARS-CoV-2 infection, in addition to population-based control measures, can reduce the risk of secondary infections and curb the spread of the infection.
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Busca de Comunicante , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , COVID-19 , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pandemias , Estudos Retrospectivos , RiscoRESUMO
Hyperuricemia/gout is a common metabolic disease in China, which is a serious threat to people's health. In clinical practice, the standardization of prevention and diagnosis and the rate of treat-to-target need to be improved. There is still a lack of education for the patients about the understanding of clinical guidelines, the disease knowledge and the importance of cooperating with doctors to carry out diagnosis and treatment. From the most concerned issues of the patients, we established the hyperuricemia/gout patient practice guideline working group with multidisciplinary physicians and patients. Seventeen opinions, as the hyperuricemia/gout patient practice guidelines, are proposed in accordance with the relevant principles of the "WHO guidelines development manual" , and with the international normative process, aiming to improve the patients compliance, improve the level of health management of the disease.
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Gota , Hiperuricemia , China , Gota/diagnóstico , Gota/terapia , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/terapia , Guias de Prática Clínica como AssuntoRESUMO
ABSTRACT: Objective To construct a discriminant analysis model based on the differential expression of multiple microRNAs ï¼miRNAsï¼ in two kinds of blood samples ï¼peripheral blood and menstrual bloodï¼ and three non-blood samples ï¼saliva, semen and vaginal secretionï¼, to form an identification solution for peripheral blood and menstrual blood. Methods Six kinds of miRNA ï¼miR-451a, miR-144-3p, miR-144-5p, miR-214-3p, miR-203-3p and miR-205-5pï¼ were selected from literature, the samples of five kinds of body fluids commonly seen in forensic practice ï¼peripheral blood, menstrual blood, saliva, semen, vaginal secretionï¼ were collected, then the samples were divided into training set and testing set and detected by SYBR Green real-time qPCR. A discriminant analysis model was set up based on the expression data of training set and the expression data of testing set was used to examine the accuracy of the model. Results A discriminant analysis statistical model that could distinguish blood samples from non-blood samples and distinguish peripheral blood samples from menstrual blood samples at the same time was successfully constructed. The identification accuracy of the model was over 99%. Conclusion This study provides a scientific and accurate identification strategy for forensic fluid identification of peripheral blood and menstrual blood samples and could be used in forensic practice.
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Líquidos Corporais , MicroRNAs , Análise Discriminante , Feminino , Genética Forense , MicroRNAs/genética , SêmenRESUMO
Using femtosecond resolution X-ray solution scattering at a free electron laser we were able to directly observe metal-metal bond cleavage upon photolysis at 400 nm of Ru3(CO)12, a prototype for the photochemistry of transition metal carbonyls. This leads to the known single intermediate Ru3(CO)11(µ-CO)*, with a bridging ligand (µCO) and where the asterisk indicates an open Ru3-ring. This loses a CO ligand on a picosecond time scale yielding a newly observed triple bridge intermediate, Ru3(CO)8(µ-CO)3*. This loses another CO ligand to form the previously observed Ru3(CO)10, which returns to Ru3(CO)12via the known single-bridge Ru3(CO)10(µ-CO). These results indicate that contrary to long standing hypotheses, metal-metal bond breakage is the only chemical reaction immediately following the photolysis of Ru3(CO)12 at 400 nm. Combined with previous picosecond resolution X-ray scattering data and time resolved infrared spectroscopy these results yield a new mechanism for the photolysis of Ru3(CO)12.
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AIMS: As a natural antimicrobial agent, Melaleuca alternifolia oil (MAO) is generally recognized to be safe and effective in the inhibition of phytopathogenic fungi. Due to lack of comprehensive studies on MAO for controlling postharvest Aspergillus, we investigated the preservative mechanism of MAO and its components against Aspergillus ochraceus in postharvest grapes to evaluate their potential effectiveness as fruit preservatives. METHODS AND RESULTS: In our study, the compositions in MAO were analysed by gas chromatography-mass spectrometry. The inhibitory effects of MAO and its main constituents against A. ochraceus were compared by scanning electron microscopy and transmission electron microscopy observation, and metabolic analysis. Two components of MAO, α-terpineol and terpene-4-alcohol, showed higher antifungal effects than MAO, of which α-terpineol caused the worst leakage of cytoplasm and most serious hyphae distortions and spore disruptions. The downregulation of metabolic pathways of A. ochraceus was strongest with α-terpineol. The best inhibitory efficacy against A. ochraceus in grapes also occurred with α-terpineol. 3-Carene showed little inhibitory effect. CONCLUSIONS: These results demonstrate that not all components in MAO possess antimicrobial effects, and α-terpineol is the main contributor of MAO's A. ochraceus inhibition effect. SIGNIFICANCE AND IMPACT OF THE STUDY: α-Terpineol may be used as an alternative natural preservative for the postharvest storage of grapes and other fruits.
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Antifúngicos/farmacologia , Aspergillus ochraceus/efeitos dos fármacos , Doenças das Plantas/prevenção & controle , Óleo de Melaleuca/farmacologia , Vitis/microbiologia , Antifúngicos/química , Monoterpenos Cicloexânicos , Cicloexenos/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Monoterpenos/farmacologia , Doenças das Plantas/microbiologia , Óleo de Melaleuca/química , Terpenos/farmacologiaRESUMO
Objective: To estimate the immune memory at 12 years after hepatitis B vaccination and its risk factors among adults. Methods: The study was conducted in 20 villages of Qudi town in Jiyang county, Shandong province, China in 2003. Hepatitis B surface antigen (HBsAg), antibody against HBsAg (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were tested for all healthy residents aged 15-40 years in these villages. Those who had no history of hepatitis B vaccination and were negative for all three indicators were divided into two groups randomly. Hepatitis B vaccine (HepB) was administrated to them on 0-6 month schedule or 0-1-6 month schedule respectively. Blood samples were obtained at one month after the last dose for each receipt and were quantitatively detected for anti-HBs. Finally a total of 629 participants completed HepB vaccination and anti-HBs testing, including 288 of two-dose group and 341 of three-dose group respectively. In 2015, an additional dose of HepB (challenge dose) was administrated to those who were negative for anti-HBs at follow-up (anti-HBs <10 mIU/ml) to evaluate the immune memory. A total of 93 blood samples, including 50 of two-dose group and 43 of three-dose group respectively, were drawn at 14 days after the challenge dose and anti-HBs was quantitatively detected. The anti-HBs geometric mean concentrations (GMCs) after the challenge dose were compared between the two groups. Multivariate linear regression model was built to find the independent risk factors associated with immune memory response (anti-HBs GMC after the challenge dose). Results: The challenge dose of HepB and post-challenge anti-HBs detection were completed among 93 participants. Totally 92 (98.92%, 92/93) participants were found holding immune memory (anti-HBs after the challenge dose was ≥10 mIU/ml). The immune memory positive rates were 100% (50/50) and 97.67% (42/43) in the two-dose group and three-dose group respectively and the corresponding anti-HBs GMC after challenge dose were 2 684.30 (95%CI: 1 721.71-4 185.08) mIU/ml and 3 527.48 (95%CI: 2 145.15-5 800.58) mIU/ml (P=0.410). The anti-HBs GMC after the challenge dose were 1 908.33 (95%CI: 1 190.01-3 060.27) mIU/ml, 4 004.20 (95%CI: 2 257.90-7 101.12) mIU/ml and 8 682.16 (95%CI: 5 813.94-12 965.36) mIU/ml among the participants whose anti-HBs titer was<4, 4-6 and 7-9 mIU/ml at follow-up, respectively (P=0.002). There was no correlation between immune schedule and anti-HBs GMC after the challenge dose; ß (95%CI) was -0.07 (-0.34-0.20), P=0.601. Conclusion: The immune memory after primary hepatitis B vaccination lasted for at least 12 years among adults. The immune memory response was independently associated with ant-HBs titer at follow-up, but might be similar between 0-6 month schedule and 0-1-6 month schedule.
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Vacinas contra Hepatite B/imunologia , Hepatite B/imunologia , Memória Imunológica , Adolescente , Adulto , China , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Humanos , Adulto JovemRESUMO
AIM: To discuss the effects and mechanism of microRNA-34a in cell apoptosis induced by osteoarthritis. METHODS: Collection of the normal and osteoarthritis synovial tissues and measurements of the miRNA-34a and TGIF2 gene expression. In the cell experiment, the cells were divided into Control, Blank and miRNA inhibitor group. The cell proliferation and apoptosis of the different groups were measured by MTT and flow cytometry and the TGIF2 protein expression in the different groups was evaluated by WB assay. The correlation between TGIF2 and miRNA-34a was analyzed by Double luciferase experiment. RESULTS: Compared with normal synovial tissues, the miRNA-34a gene expression was significantly up-regulated and TGIF2 gene expression was significantly suppressed in osteoarthritis synovial tissues (p < 0.001, respectively). The cell proliferation was significantly depressed and the cell apoptosis rate was significantly increased in miRNA inhibitor group compared with the Control group (p < 0.001, respectively). Using the WB assay it was shown that the TGIF2 protein expression of miRNA inhibitor group was significantly suppressed compared with that of Control group (p < 0.01). By Double luciferase assay, TGIF2 gene was one target gene of miRNA-34a. CONCLUSION: miRNA-34a could induce osteoarthritis synovial cell apoptosis via regulation of TGIF2 in vitro (Fig. 6, Ref. 29).
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Apoptose , Proteínas de Homeodomínio , MicroRNAs , Osteoartrite , Proteínas Repressoras , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/fisiologia , Humanos , MicroRNAs/fisiologia , Osteoartrite/metabolismo , Proteínas Repressoras/fisiologiaRESUMO
AIMS: Aspergillus aculeatus, a pathogen of peaches, can cause soft rot and lead to economic losses in agricultural production. However, studies on the prevention of soft rot caused by A. aculeatus have rarely been reported. Tricyclazole (TCZ) is a fungicide that has been widely used in disease prevention of various crops but the inhibitory mechanism of TCZ on A. aculeatus is unknown. Our aim was to determine the effects of TCZ on A. aculeatus. METHODS AND RESULTS: In our study, TCZ inhibited the growth of fungal colonies when applied at 0·5-6 mmol l-1 and inhibited the production of melanin at 3 mmol l-1 . Conidia exposed to TCZ were less effective at causing the disease in inoculated samples, and electrical conductivity, divulgation of nucleic acids and proteins rose with increasing concentrations of TCZ. Microscopic results suggest that TCZ damages not only the cell wall but also the cell membrane. Results of qRT-PCR showed that TCZ had no significant effect on the regulation of genes coding for laccase, apoptosis and hypothetical protein; however, it significantly down-regulated genes coding for cellulase, chitinase and sterol. CONCLUSIONS: Tricyclazole can influence the pathogenic ability of A. aculeatus by damaging the cell structure of hyphae and conidia, reducing the melanin production, and altering the expression of pathogenic-related gene. SIGNIFICANCE AND IMPACT OF THE STUDY: The results explained the potential cause and mechanism TCZ produced in A. aculeatus. Our research offers scientific insights into future research interest relative to using TCZ in the treatment of soft rot caused by A. aculeatus.
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Esophageal cancer and its treatment can cause serious morbidity/toxicity. These effects on health-related quality of life (HRQOL) can be measured using disease-specific scales such as FACT-E, generic scales such as EQ-5D-3L, or through symptoms. In a two-year cross-sectional study, we compared HRQOL across esophageal cancer patients treated in an ambulatory clinic and across multiple disease states, among patients with all stages of esophageal cancer. Consenting patients completed FACT-E, EQ-5D, a visual analog scale, and patient reported (PR)-ECOG. Symptom complexes were constructed from FACT-E domains. Responses were categorized by disease state: pre-, during, and post-treatment, surveillance, progression, and palliative chemotherapy. Spearman correlation and multivariable linear regression characterized these associations. In total, 199 patients completed 317 questionnaires. Mean FACT-E and subscale scores dropped from baseline through treatment and recovered during post-treatment surveillance (P < 0.001); EQ-5D health utility scores (HUS) displayed a similar pattern but with smaller differences (P = 0.07), and with evidence of ceiling effect. Among patients with stage II/III esophageal cancer, mean EQ-5D HUS varied across disease states (P < 0.001), along with FACT-E and subscales (P < 0.001). Among patients with advanced disease, there was no significant difference between baseline and on-treatment total scores, but improved esophageal cancer-specific scales were noted (P = 0.003). Strong correlation was observed between EQ-5D and FACT-E (R = 0.73), along with physical and functional subscales. In addition, the association between FACT-E and EQ-5D HUS was maintained in a multivariable model (P < 0.001). We interpret these results to suggest that in a real-world clinic setting, FACT-E, EQ-5D HUS, and symptoms were strongly correlated. Most HRQOL and symptom parameters suggested that patients had worse HRQOL and symptoms during curative therapy, but recovered well afterwards. In contrast, palliative chemotherapy had a neutral to positive impact on HRQOL/symptoms when compared to their baseline pre-treatment state.
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Neoplasias Esofágicas/diagnóstico , Nível de Saúde , Qualidade de Vida , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estatísticas não Paramétricas , Inquéritos e QuestionáriosRESUMO
Objective: In order to study the diagnosis and treatment value of chelating anti-IL-1ß mAb-SPIONs in temporal lobe epilepsy model induced by lithium chlorid and pilocarpine. Methods: Forty-five temporal lobe epilepsy model rats were randomly and equally divided into saline group, plain-SPIONs group, anti-IL-1ß mAb-SPIONs group. Each group was injected with equal particles at day 3 and day 14 after the onset of seizures. MRI were conducteds before and 4 hours after particles injection and T2 values were measured. The distribution of iron particles in the epileptic tissue was observed and the neuronal loss, astrocyte proliferation and microglia activation were detected. The expressions of IL-1ß and NF-κBp65 in each group were detected meanwhile. Results: At day 14 after seizure, the value of T2 was 84±14 after injecting anti-IL-1ß mAb-SPIONs. Compared with the control group, the value of T2 obviously declined. These phenomena of neuron loss, astrocyte proliferation and microglia activation had been improved obviously. IL-1ßand NF-κBp65 expression also significantly reduced. Conclusion: Anti-IL-1ß mAb-SPIONs can penetrate blood brain barrier and plays an important role in targeting positioning and targeting therapy in temporal lobe epilepsy.
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Epilepsia do Lobo Temporal , Animais , Modelos Animais de Doenças , Hipocampo , Interleucina-1beta , Pilocarpina , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: The aim of this study was to evaluate the effects and mechanism of miRNA-31 in synovial cells apoptosis induced by RA. METHODS: The miRNA-31 gene expressions were extracted from synovial tissues of normal and RA patients by RT-PCR and H et E staining. The synovial cells of RA patients were isolated and randomly divided into Control, Blank and miRNA groups. The cell apoptosis of difference groups were measured by flow cytometry; the TNF-α and IL-1ß concentrations of difference groups were measured by Elisa assay; TLR4 and NF-κB proteins expressions were measured by WB assay and the correlation between TLR4 and miRNA-31 were evaluated by double luciferase target experiment. RESULTS: The miRNA-31 gene expression was significantly suppressed in RA tissues (p<0.001); Compared with control group, the cell apoptosis rate of miRNA group was significantly suppressed (p<0.001); TNF-α and IL-1ß concentrations were significantly down-regulation in culture fluid (p<0.001, respectively) and TLR4 and NF-κB proteins expressions were significantly depressed (p<0.001, respectively) in miRNA group. By double luciferase target experiment, the TLR4 was a target gene of miRNA-31. CONCLUSION: miRNA-31 is a key role in synovial cells apoptosis induced by RA (Fig. 7, Ref. 23).
Assuntos
Apoptose/genética , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Expressão Gênica/genética , MicroRNAs/genética , Líquido Sinovial/citologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Interleucina-1beta/metabolismo , NF-kappa B/metabolismo , Estatística como Assunto , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Sperm-mediated gene transfer(SMGT) is a simple method for producing transgenic animals. Due to the lack of repeatability in spermatozoa binding and internalization of exogenous DNA, the efficiency of SMGT is still low. Considering this point, the present work aims to develop a method for evaluating the spermatozoa capacity of binding exogenous DNA after co-incubation with DNA. The main approach is using a Cy5-labelled DNA to trace the exogenous DNA and assess the ability of spermatozoa to take up exogenous DNA. Using this technique, we found that the percentage of spermatozoa that are binding and uptaking DNA is higher at concentration of 10 µg/mL and 100 µg/mL than 5 µg/mL, 1 µg/mL and 0 µg/mL after incubation with Cy5-DNA for 30min at 37oC. After fertilization, the DNA fluorescence signal was also detected in zygotes in groups where spermatozoa were incubated with 10 µg/mL and 100 µg/mL of Cy5-DNA. These results showed a simple and convenient method to trace the exogenous DNA in spermatozoa and zygote when compared to conventional methods of labeling DNA during fertilization, resulting in a real-time observation of the exogenous DNA in spermatozoa and zygote.