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OBJECTIVE: Abnormalities in the gray matter structure of cerebral small vessel disease (CSVD) have been observed throughout the brain. However, whether cortico-cortical connections exist between regions of gray matter atrophy in patients with CSVD has not been fully elucidated. This question was tested by comparing the gray matter covariance networks in CSVD patients with and without cognitive impairment (CI). METHODS: We performed multivariate modeling of the gray matter volume measurements of 61 patients with CI (CSVD-CI), 85 patients without CI (CSVD-NC), and 108 healthy controls using source-based morphological analysis (SBM) to obtain gray matter structural covariance networks at the population level. Then, correlations between structural covariance networks and cognitive functions were analyzed in CSVD patients. Finally, a support vector machine (SVM) classifier was used with the gray matter covariance network as a classification feature to identify CI among the CSVD population. RESULTS: The results of the analysis of all the subjects showed that compared with healthy controls, the expression of the thalamic covariance network, cerebellum covariance network, and calcarine cortex covariance network was reduced in patients with CSVD. Moreover, CSVD-CI patients showed a significant reduction in the expression of the thalamic covariance network, encompassing the thalamus and the parahippocampal gyrus, relative to CSVD-NC patients, which persisted after excluding CSVD patients with thalamic lacunes. In patients with CSVD, cognitive functions were positively correlated with measures of the thalamic covariance network. More than 80% of CSVD patients with CI were correctly identified by the SVM classifier. INTERPRETATION: Our findings provide new evidence to explain the distribution state of gray matter reduction in CSVD patients, and the thalamic covariance network is the core region for early gray matter reduction during the development of CSVD disease, which is related to cognitive deficits. Reduced expression of thalamic covariance networks may provide a neuroimaging biomarker for the early identification of cognitive impairment in CSVD patients.
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Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Substância Cinzenta , Imageamento por Ressonância Magnética , Tálamo , Humanos , Masculino , Feminino , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/patologia , Doenças de Pequenos Vasos Cerebrais/complicações , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/patologia , Idoso , Pessoa de Meia-Idade , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Tálamo/diagnóstico por imagem , Tálamo/patologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/patologia , Máquina de Vetores de SuporteRESUMO
Gadolinium chelates for tumor magnetic resonance imaging (MRI) face challenges such as inadequate sensitivity, lack of selectivity, and risk of Gd leakage. This study presents a single-atom Gd nano-contrast agent (Gd-SA) that enhances tumor MRI. Isolated Gd atoms coordinated by six N atoms and two O atoms are atomically dispersed on a hollow carbon nanosphere, allowing the maximum utilization of Gd atoms with reduced risk of toxic Gd ion leakage. Owning to the large surface area and fast exchange of relaxed water molecules, Gd-SA shows excellent T1-weighted magnetic resonance enhancement with a r1 value of 11.05 mM-1 s-1 at 7 T, which is 3.6 times that of the commercial gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). In vivo MRI results show that the Gd-SA has a higher spatial resolution and a wider imaging time window for tumors than Gd-DTPA, with low hematological, hepatic, and nephric toxicities. These advantages demonstrate the great potential of single-atom Gd-based nanomaterials as safe, efficient, and long-term MRI contrast agents for cancer diagnosis.
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Gadolínio DTPA , Neoplasias , Humanos , Gadolínio , Imageamento por Ressonância Magnética/métodos , Meios de Contraste , Neoplasias/diagnóstico por imagemRESUMO
Distal gastrectomy (DG) and total gastrectomy (TG) are the most common types of radical surgery for patients with middle-third gastric cancer (MTGC). However, the indications and benefits of the two procedures still remain controversial. The present meta-analysis aimed to compare the surgical and oncological outcomes of DG and TG in the treatment of MTGC. A rigorous literature review was performed in the databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Chinese BioMedical Literature to retrieve studies published up to February 2022. The Newcastle-Ottawa Scale was used to assess the quality of included studies and a meta-analysis was performed using RevMan 5.3 software. A total of 12 retrospective studies performing comparisons of DG and TG were included in the present meta-analysis. For patients who underwent DG, a lower rate of overall post-operative complications, anastomosis leakage and intro-abdominal infection was determined. No significant difference was observed between DG and TG in the 5-year overall survival when the proximal resection margin ranged from 3 to 5 cm. Although DG was associated with a higher 5-year overall survival rate when compared to TG, there was no significant difference in the stratified analyses by TNM stage. In conclusion, the prognosis of MTGC did not depend on the extent of gastrectomy. With lower complications and acceptable oncological outcomes, DG was a safe and feasible surgical procedure for MTGC when a negative proximal margin was confirmed.
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BACKGROUND: Numerous case-control studies have reported associations between interleukin-17 (IL-17) polymorphisms and colorectal cancer; however, the results were inconsistent. The aim of this meta-analysis was to further clarify the effects of IL-17 polymorphisms on colorectal cancer susceptibility. MATERIALS AND METHOD: Relevant studies were extracted from the electronic databases PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CMB) up to April 2021. The odds ratio and 95% confidence interval were used to estimate the strength of the associations. RESULTS: Ten articles including 2599 cases and 2845 controls were enrolled in our research after strict literature screening. Highly significant associations between the IL-17A rs2275913 polymorphism and increased colorectal cancer susceptibility were observed in all five gene models (allelic, dominant, recessive, homozygous, and heterozygous models), and subgroup analysis based on ethnicity revealed that these associations existed not only in the Asian population but also in the Caucasian population. However, the results showed no significantly elevated colorectal cancer risk correlated with the IL-17F rs763780 polymorphism, and a slightly lower colorectal cancer susceptibility for the Caucasian population was discovered in the recessive and homozygous models of this mutation. CONCLUSION: The IL-17A rs2275913 polymorphism may be an independent risk factor contributing to colorectal cancer susceptibility, while the IL-17F rs763780 polymorphism may decrease susceptibility to colorectal cancer. Future studies with large-scale samples are warranted to identify these associations.
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Neoplasias Colorretais , Interleucina-17 , Humanos , Estudos de Casos e Controles , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Interleucina-17/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Chemoimmunotherapy using nanotechnology has shown great potential for cancer therapy in the clinic. However, uncontrolled transportation and synergistic responses remain challenges. Here, a self-assembled selenopeptide nanoparticle that strengthens tumor chemoimmunotherapy through the activation of natural killer (NK) cells by the oxidative metabolite of the selenopeptide is developed. With the advantages of the enzyme-induced size-reduction and the reactive-oxygen-species-driven deselenization, this selenopeptide is able to deliver therapeutics, e.g., doxorubicin (DOX), to solid tumors and further activate the NK cells in a programmed manner. Importantly, in vitro and in vivo results prove the mutual promotion between the DOX-induced chemotherapy and the selenopeptide-induced immunotherapy, which synergistically contribute to the improved antitumor efficacy. It is anticipated that the selenopeptide may provide a type of promising stimuli-responsive immune modulator for versatile biomedical applications.
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Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Humanos , Imunoterapia , Células Matadoras Naturais , Nanomedicina , Neoplasias/tratamento farmacológico , Neoplasias/metabolismoRESUMO
Traditional luminescent liquid crystals (LLCs) suffer from fluorescence quenching caused by aggregation, which greatly limits their further application. In this work, a kind of novel LLCs (named carbonized polymer dot liquid crystals (CPD-LCs)) are designed and successfully synthesized through grafting the rod-shaped liquid crystal (LC) molecules of 4'-cyano-4-(4â³-bromohexyloxy) biphenyl on the surface of CPDs. The peripheral LC molecules not only increase the distance between different CPDs to prevent them from aggregating and reduce intermolecular energy resonance transfer but also make this LLC have an ordered arrangement. Thus, the obtained CPD-LCs show good LC property and excellent high luminous efficiency with an absolute photoluminescence quantum yield of 14.52% in the aggregated state. Furthermore, this kind of CPD-LC is used to fabricate linearly polarized devices. The resultant linearly polarized dichroic ratio (N) and polarization ratio (ρ) are 2.59 and 0.44, respectively. Clearly, this type of CPD-LC shows promising applications for optical devices.
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BACKGROUND: It is not well clear how psychosocial factors like depressive symptoms, social support affect quality of life in rural elderly in China. This study aimed to investigate the mediating role of depressive symptoms in the association between social support and quality of life. METHODS: Cross-sectional data of 420 rural elderly were taken from four villages in Hangzhou City. They were interviewed with a demographic questionnaire, the Patient Health Questionnaire (PHQ-9) for depression, the Medical Outcomes Study Social Support Survey (MOS-SSS) for social support, and the short version of World Health Organization Quality of Life Assessment (WHOQOL-BREF) for quality of life. Mediation was examined by a nonparametric Bootstrapping method, controlling for socioeconomic variables. RESULTS: Poor quality of life was associated with low social support and increased depressive symptoms. A significant indirect effect of social support existed through depression in relation to quality of life (ab = 0.0213, 95% CI [0.0071, 0.0421]), accounting for 9.5% of the effect of social support on quality of life. Approximately 4.8% of the variance in QOL was attributable to the indirect effect of social support through depressive symptoms. CONCLUSIONS: Depressive symptoms mediated the impact of social support on quality of life among rural older adults.
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Depressão/psicologia , Qualidade de Vida , Apoio Social , Inquéritos e Questionários/normas , Idoso , Idoso de 80 Anos ou mais , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População Rural/estatística & dados numéricos , Organização Mundial da SaúdeRESUMO
BACKGROUND: A large number of studies have been conducted to investigate associations between genetic variants and esophageal cancer risk in the past several decades. However, findings from these studies have been generally inconsistent. We aimed to provide a summary of the current understanding of the genetic architecture of esophageal cancer susceptibility. METHODS: We performed a comprehensive field synopsis and meta-analysis to evaluate associations between 95 variants in 70 genes or loci and esophageal cancer risk using data from 304 eligible publications, including 104,904 cases and 159,797 controls, through screening a total of 21,328 citations. We graded levels of cumulative epidemiologic evidence of a significant association with esophageal cancer using the Venice criteria and false-positive report probability tests. We constructed functional annotations for these variants using data from the Encyclopedia of DNA Elements Project and other databases. RESULTS: Thirty variants were nominally significantly associated with esophageal cancer risk. Cumulative epidemiologic evidence of a significant association with overall esophageal cancer, esophageal squamous cell carcinoma, or esophageal adenocarcinoma was strong for 13 variants in or near 13 genes (ADH1B, BARX1, CDKN1A, CHEK2, CLPTM1L, CRTC1, CYP1A1, EGF, LTA, MIR34BC, PLCE1, PTEN, and PTGS2). Bioinformatics analysis suggested that these variants and others correlated with them might fall in putative functional regions. CONCLUSIONS: Our study summarizes the current literature on the genetic architecture of esophageal cancer susceptibility and identifies several potential polymorphisms that could be involved in esophageal cancer susceptibility. IMPACT: These findings provide direction for future studies to identify new genetic factors for esophageal cancer.
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Adenocarcinoma/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Predisposição Genética para Doença , Adenocarcinoma/epidemiologia , Biologia Computacional , Neoplasias Esofágicas/epidemiologia , Carcinoma de Células Escamosas do Esôfago/epidemiologia , Humanos , Polimorfismo Genético , Fatores de RiscoRESUMO
Objectives: To explore the transfer effects of cognitive training on working memory among older Chinese adults with mild cognitive impairment (MCI). Methods: Sixty-two MCI participants aged more than 60 years old were recruited by holding recruitment sessions in communities in China [33 for cognitive training, and 29 for mental leisure activities (MLA) control]. Cognitive functions, including working memory, execution function, reasoning ability, verbal ability, ability of daily living, were measured at three time-points (baseline, post-training and 3 months after training). Results: Compared to the MLA control, the cognitive training group showed significant effects in both the trained (working memory) and untrained (execution function and ability of daily living) domains. The effects of cognitive training on overall cognitive function, working memory and daily life ability of daily living of MCI could be maintained for at least 3 months, even without the cognitive training. Besides, complete mediating effects of cognitive training were found in executive function through working memory and working memory in ability of daily living though executive function, which suggests the presence of transfer effect of cognitive training. Conclusions: The present study supported that cognitive training could effectively improve working memory in elders with MCI. The training effects on working memory could transfer to other untrained areas (such as executive function), which also improved the comprehensive ability (ability of daily living). And the effects of training could largely persist for 3 months.
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OBJECTIVE: Based on eastern philosophy, mindfulness is becoming popular for human being's mental health and well-being in western countries. In this study, we proposed to explore the effectiveness and potential pathway of mindfulness-based training (MBT) on Chinese Non-clinical higher education students' cognition and emotion. METHODS: A paired control design was used. 48 higher education students (24 in MBT group, 24 in control group) were recruited in the study. The MBT group engaged in a 12-week MBT. A package of measurements, including sustained attention tasks (The Continuous Performance Test, CPT), executive function task (Stroop) for cognitive functions, the self-reported mindfulness levels (The Mindful Attention Awareness Scale, MAAS) and emotion (The Profile of Mood States, POMS), were apply for all participants at baseline and every 4 weeks during next 12 weeks. RESULTS: There were no differences in baseline demographic variables between two groups. Over the 12-week training, participants assigned to MBT group had a significantly greater reduction in CPT reaction time (Cohen's d 0.72), significantly greater improvement in positive emotion (Vigor-Activity, VA) (Cohen's d 1.08) and in MAAS (Cohen's d 0.49) than those assigned to control group. And, MAAS at 4th week could significantly predict the CPT RT and VA at 8th week in the MBT group. VA at 4th week could significantly predict the CPT RT at 8th week (B = 4.88, t = 2.21, p = 0.034, R2 = 0.35). CONCLUSION: This study shows the efficiency of 12-week MBT on Chinese Non-clinical students' cognition and emotion. Mindfulness training may impact cognition and emotion through the improvement in mindfulness level, and may impact cognition through the improvement in positive emotion.
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OBJECTIVES: Both depression and hypertension (HTN) are prevalent, costly, and destructive, and frequently coexist among the aging population of China. This study aimed to examine the role that treatment adherence plays in blood pressure control in older adult Chinese with depression. METHODS: Data for these analyses were taken from a randomized control trial of a collaborative depression care management intervention conducted in rural villages of Zhejiang Province, China with older adults who had comorbid depression and HTN. They included baseline assessments of 2362 subjects ages ≥60 years, whose blood pressure and depression were measured using a calibrated manual sphygmomanometer and the Chinese version of the 17-item Hamilton Depression Rating Scale (HDRS-17), respectively. Treatment adherence was identified by a single question asking whether patients on occasion did not take their medicine. RESULTS: Uncontrolled HTN was associated with older age (t = 3.10, P<0.01), higher HDRS-17 score (t = 5.76, P<0.01), and higher rates of non-adherence to HTN treatment (χ2 = 21.34, P<0.01). Logistic regression models indicated that adherence accounted for 39.4% of the total effect between depression and HTN. Specifically, those with poor adherence were at 1.417 greater odds of having their HTN uncontrolled compared with those with good adherence. CONCLUSIONS: Hypertension control in older adults with depression is complicated by nonadherence to treatment. In addition to diagnosing and treating depression in their older adult patients, primary care physicians can optimize blood pressure control by identifying and addressing their patients' adherence to recommendations for HTN management.
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Depressão/epidemiologia , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Cooperação do Paciente , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Pressão Sanguínea , Determinação da Pressão Arterial , China/epidemiologia , Comorbidade , Feminino , Humanos , Hipertensão/fisiopatologia , Modelos Logísticos , Masculino , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , População RuralRESUMO
BACKGROUNDS AND PURPOSE: Robotic surgery has been applied in gastric carcinoma over a decade. Although a series of studies were performed to investigate the short-term outcomes of robot-assisted gastrectomy, few papers were in view of long-term outcomes. The current study was aimed to explore the oncological outcomes of robotic gastrectomy for gastric cancer patients. METHODS: A total of 606 gastric cancer patients who underwent robot-assisted gastrectomy during March 2010 through March 2017, were enrolled in this research. The clinicopathologic characteristics, surgical procedures along with follow-up information and prognostic factors were recorded in detail. The disease-free survival and overall survival rates were tested by Kaplan-Meier analysis. RESULTS: All the patients underwent the robotic surgery including 15 proximal gastrectomies, 403 distal gastrectomies, 169 total gastrectomies and 19 remnant gastrectomies. Fifiy-six (9.24%) patients were lost in the follow-up process (3-87 months, a media of 42 months). There were 119 recurrences observed, including 55 local recurrences, 51 peritoneal metastasis and 13 distant metastasis. The 3-year disease-free survival and overall survival were 73.60% and 74.24%, while the 5-year disease-free survivorship and overall survival rates were 68.73% and 69.33%. The 5-year overall survival rates grouped based on TNM stage were 96.58% for IA, 88.16% for IB, 87.03% for IIA, 80.62% fo IIB, 58.50% for IIIA, 48.62% for IIIB, 45.32% for IIIC and 17.03% for IV. CONCLUSION: Robot-assisted gastrectomy is a valuable procedure for gastric cancer patients. Beside its feasibility and safety, it reveals an acceptable long-term clinical outcome.
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Patient beliefs about depression and its treatment in primary care clinics in China influence the delivery of care. Our objective was to investigate primary care patients' beliefs about depression and its treatment as well as help-seeking preferences regarding depression in China to aid in the development and promotion of interventions that are acceptable to patients with depression. 100 primary care nurses used the Public Knowledge and Beliefs Survey Package (PKBSP) to assess patients in the primary care clinic waiting rooms. Of the 2639 patients, 15.5% were depressed. Patients with higher education level were less likely to be depressed. Differences in beliefs were significantly associated with age, education level and depression status, but no significant differences were found on gender. Help-seeking preferences were also significantly associated with age, education level and depression status. Patients screened with PHQ-9 positive depression were less willing to endorse "take antidepressants" and "consult a non-medical practitioner" than non-depressed patients. However, they were more willing to endorse "consult a psychotherapist". Patient beliefs about depression and its treatment highlight a need for modification of current paradigms, practices, and approaches to improve the acceptability of depression care provision. Efforts to increase collaboration between primary care physicians and mental health professionals are needed.
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Cultura , Depressão/psicologia , Depressão/terapia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Preferência do Paciente/psicologia , Atenção Primária à Saúde , Adolescente , Adulto , Idoso , China/etnologia , Depressão/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Preferência do Paciente/etnologia , Atenção Primária à Saúde/tendências , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVES: This study aimed to examine the reliability and validity of the Six-Item Screener (SIS) in screening cognitive impairment (CI) compared to the Mini-Mental State Examination (MMSE) in primary care settings in China. METHODS: Participants (n = 2556, aged 60 years or older) from 30 primary care settings in Hangzhou, China, were recruited and screened using the SIS. They had a mean age of 71.6 ± 8.7 years, 50% were females, and 73% had education fewer than 5 years. A number of 373 screened participants received the MMSE assessment after the screening. RESULTS: The correlation coefficients between the six items of the SIS and its total score ranged from 0.17 to 0.78. The correlation between the total score of SIS and MMSE was 0.70. The Cronbach's α coefficient of the SIS was 0.70. The receiver operating characteristic analysis using MMSE as the golden standard had the optimal cut-off score of 3, with sensitivity of 0.86 and specificity of 0.87, and the area under the curve (AUC) was 0.93. CONCLUSION: The SIS performs well compared with the MMSE for screening of individuals with CI in primary care settings in China.
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Disfunção Cognitiva/diagnóstico , Testes Neuropsicológicos/normas , Atenção Primária à Saúde/métodos , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência/normas , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
AIM: To perform a meta-analysis to investigate the association between cyclooxygenase-2 (COX-2) -1195G>A gene polymorphism and gastrointestinal cancers. METHODS: Publications related to the COX-2 -1195G>A gene polymorphism and gastrointestinal cancers published before July 2016 were retrieved from PubMed, EMBASE, Web of Science, China Biological Medicine Database, China National Knowledge Infrastructure, and CQVIP Database. Meta-analysis was performed using Stata11.0 software. The strength of the association was evaluated by calculating the combined odds ratios (ORs) and the corresponding 95%CIs. The retrieved publications were excluded or included one by one for sensitivity analysis. In addition, the funnel plot, Begg's rank correlation test, and Egger's linear regression method were applied to analyse whether the included publications had publication bias. RESULTS: A total of 24 publications related to the COX-2 -1195G>A gene polymorphism were included, including 28 studies involving 11043 cases and 18008 controls. The meta-analysis results showed that the COX-2 -1195G>A gene polymorphism significantly correlated with an increased risk of gastrointestinal cancers, particularly gastric cancer (A vs G: OR = 1.35; AA/AG vs GG: OR = 1.54; AA vs GG/AG: OR = 1.43; AA vs GG: OR = 1.80; AG vs GG: OR = 1.35). Compared to the Caucasian population in America and Europe, the COX-2 -1195G>A gene polymorphism in the Asian population (A vs G: OR = 1.30; AA/AG vs GG: OR = 1.50; AA vs GG/AG: OR = 1.35; AA vs GG: OR = 1.71; AG vs GG: OR = 1.37) significantly increased gastrointestinal cancer risk. The sensitivity analysis (P < 0.05) and the false positive report probability (P < 0.2) confirmed the reliability of the results. CONCLUSION: The results showed that the COX-2 -1195G>A gene polymorphism might be a potential risk factor for gastrointestinal cancers. Further validation by a large homogeneous study is warranted.
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Ciclo-Oxigenase 2/genética , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/genética , Polimorfismo de Nucleotídeo Único , Povo Asiático , Reações Falso-Positivas , Neoplasias Gastrointestinais/etnologia , Predisposição Genética para Doença , Genótipo , Humanos , Razão de Chances , Fatores de Risco , Tamanho da AmostraRESUMO
Gastric cancer is the most common cancer and the most frequent cause of cancer death worldwide. Several studies have identified the role of thymidylate synthase (TS) 5'- and 3'-UTR and gastric cancer susceptibility; however, the results still remain inconclusive. The purpose of this meta-analysis was to reinvestigate this correlation. In the present study, online databases were searched to retrieve relevant articles published between January 2000 and 2016. The odds ratio (OR) and 95% confidence interval (CI) were employed to calculate the strength of association. Overall, a total of 13 articles were screened out, including 2382 gastric cancer patients and 3171 healthy controls. We found that polymorphisms of TS 5'-UTR 2R (double repeats)/3R (triple repeats) of a 28-bp sequence (11 articles) and 3'-UTR del6/ins6 (seven articles) were not significantly associated with increased risk of gastric cancer. Subgroup analysis by ethnicity showed that 2R allele and 2R/2R genotype in TS 5'-UTR were associated with gastric cancer susceptibility in Caucasian and African populations; del6 allele, del6/del6 and del6/ins6 genotypes were correlated with gastric cancer in Caucasian population. In conclusion, our result suggested that TS polymorphisms might be the risk factors for gastric cancer risk in Caucasian population, although this association needs further study, and future large-scale researches are still required.
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Regiões 3' não Traduzidas/genética , Regiões 5' não Traduzidas/genética , Predisposição Genética para Doença , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Timidilato Sintase/genética , População Negra/genética , Humanos , Razão de Chances , Polimorfismo Genético , Fatores de Risco , População Branca/genéticaRESUMO
The metastasis of tumor cells to distant organs is an ominous feature of gastric cancer. However, the molecular mechanisms underlying the invasion and metastasis of gastric cancer cells remain elusive. In this study, we found that the expression of ATG4A, an autophagy-regulating molecule, was significantly increased in gastric cancer tissues and was significantlycorrelated with the gastric cancer differentiation degree, tumor invasion and lymph node metastasis. ATG4A over-expression significantly promoted gastric cancer cell migration and invasion in vitro and metastasis in vivo, as well as promoted gastric cancer cell stem-like properties and the epithelial-mesenchymal transition (EMT) phenotype. By contrast, ATG4A knockdown inhibited the migration, invasion and metastasis of cancer cells, as well as the stem-like properties and EMT phenotype. Mechanistically, ATG4A promotes gastric cancer cell stem-like properties and the EMT phenotype through the activation of Notch signaling not via autophagy, and using the Notch signaling inhibitor DAPT attenuated the effects of ATG4A on gastric cancer cells. Taken together, these findings demonstrated that ATG4A promotes the metastasis of gastric cancer cells via the Notch signaling pathway, which is an autophagy-independent mechanism.
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Proteínas Relacionadas à Autofagia/metabolismo , Cisteína Endopeptidases/metabolismo , Transição Epitelial-Mesenquimal , Células-Tronco Neoplásicas/patologia , Neoplasias Gástricas/metabolismo , Idoso , Animais , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Transplante de Neoplasias , Fenótipo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Estômago/patologia , Neoplasias Gástricas/genética , Vimentina/metabolismoRESUMO
INTRODUCTION: mites allergic asthma is caused by exposure to home dust mite (HDM). Der f 3 is believed to be one of the major allergens in mites allergic asthma. The work was to identify the immune characteristics of Der f 3 epitope-based vaccine containing T cell and B cell epitopes. METHODS: T cell lines were generated from peripheral blood mononuclear cells of Der f 3 allergic patients. Three T cell epitopes and five B cell epitopes of Der f 3, which we identified previously, were selected to design a polypeptide (named Der f3-peptides). DNA constructions encoding these Der f 3-peptides were expressed in Escherichia coli. The T cell lines were stimulated with the peptides and tested for proliferative capacity and cytokine production. RESULTS: plasmid pET28a (+)-Der f 3-peptides was constructed and expressed in E. coli BL21, and the Der f3-peptides protein was purified and confirmed by Western blotting. The Der f 3-peptides were recognized by the T cell clones from allergic patients. SI value of Der f 3 group and Der f 3-peptides group were both higher than that of PBS group (P<0.05). The Der f 3 and Der f 3 peptides induced secretions of IL-4 and IL-5 were decreased compared with that of PBS group (P<0.05). The capacity of IgE-binding to Der f 3-peptides (41.25±5.67) µg/ml was decreased dramatically compared with that of Der f 3 (83.60 ± 10.92) µg/ml (P < 0.05). CONCLUSIONS: our results demonstrate that several major T cell epitopes and B cell epitopes of Der f 3 can be valuable for designing the peptide-based immunotherapeutics for the mites allergic asthma.
Introducción: el asma alérgica está causada por la exposición a los ácaros del polvo casero (HDM). Der f 3 se cree que es uno de los principales alérgenos en los ácaros del asma alérgica. El trabajo consistió en identificar las características inmunológicas de la vacuna basada en epítopo-Der f 3 que contienen las células T y las células B. Métodos: se generaron líneas de células T a partir de células mononucleares de sangre periférica de pacientes alérgicos a Der f 3. Tres epítopos de células T y cinco epítopos de células B de Der f 3, que hemos identificado previamente, fueron seleccionados para diseñar un polipéptido (denominados péptidos Der f 3). Construcciones de DNA que codifican estos péptidos Der f 3 se expresaron en Escherichia coli. Las líneas de células T se estimularon con los péptidos y se utilizaron en el ensayo por su capacidad proliferativa y la producción de citoquinas. Resultados: el plásmido pET28a (+) - Der f 3-péptidos se construyó y se expresaron en E. coli BL21, y la proteína de Der f 3-péptidos se purificó y se confirmaron mediante transferencia de Western. Los Der f 3-péptidos fueron reconocidos por los clones de células T procedentes de pacientes alérgicos. Valor SI de Der f 3 grupo y f grupo 3-péptidos Der eran tanto mayor que la del grupo de PBS (P.
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Epitopos de Linfócito T/imunologia , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/prevenção & controle , Vacinas/imunologia , Vacinas/uso terapêutico , Adulto , Sequência de Aminoácidos , Animais , Sequência de Bases , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Citocinas/biossíntese , Feminino , Humanos , Masculino , Linfócitos T/imunologia , Linfócitos T/metabolismo , Vacinas Sintéticas/imunologia , Adulto JovemRESUMO
BACKGROUND: Previous researchers have identified that the chemokine interleukin-17 (IL-17) was associated with survival time of patients with gastric cancer, but the roles of its receptors (IL-17R) in gastric cancer remain unknown. Our studies were designed to clarify the function of IL-17RA and to explore their potential role in gastric cancer. MATERIALS AND METHODS: The expression of IL-17RA was determined in primary gastric cancer tissues (n=101) using Real-time RT-PCR, immunohistochemistry, and western blotting. To investigate the functional significance of IL-17RA expression, IL-17RA expression and clinical parameters, multivariate survival was analyzed in patients with gastric cancer. RESULTS: IL-17RA was overexpression in gastric cancer tissues compared with adjacent normal tissues (P<0.05). The elevated expression level of IL-17RA was observed correlated significantly with tumor progression (P=0.003), Lymphatic invasion (P=0.019), lymphoid nodal status (P=0.001), distant metastasis (P<0.001) of gastric cancer patients, TNM stage (P=0.0013) and was one of the independent prognostic factors for patient's overall survival. CONCLUSIONS: These results demonstrated that the expression of IL-17RA plays an important role in gastric cancer progression, migration and prognosis of gastric cancer. The IL-17-IL-17RA signaling mechanism may be a potential novel target.
Assuntos
Biomarcadores Tumorais/análise , Receptores de Interleucina-17/análise , Neoplasias Gástricas/química , Idoso , Biomarcadores Tumorais/genética , Western Blotting , Movimento Celular , Distribuição de Qui-Quadrado , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Interleucina-17/genética , Fatores de Risco , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Fatores de Tempo , Resultado do Tratamento , Regulação para CimaRESUMO
BACKGROUND: A number of studies have been conducted to investigate associations between genetic polymorphisms in interleukin-17 (IL-17) pathway and the risk of gastrointestinal diseases. Results, however, have been inconclusive. We aimed to evaluate these associations through a meta-analysis. METHODS: We searched electronic databases (PubMed, Embase, Web of Science, CBM and CNKI) to identify papers, published before October 2014, on associations between polymorphisms in the IL-17 pathway genes (rs2275913, rs763780, rs3748067, rs3819025, rs9382084, rs12203582 and rs8193036) and the risk of gastrointestinal diseases. We estimated the strength of candidate associations through calculating pooled odds ratios (ORs) and 95% confidence intervals (CIs). A test of heterogeneity, a false-positive report probability (FPRP) test, sensitivity analyses and examination for bias were further conducted to evaluate cumulative evidence of these associations. RESULTS: We identified 25 eligible case-control studies retrieved from 16 articles involved in a total of 4507 cases and 5733 controls. Of them, IL-17 (-197G/A) polymorphism (rs2275913) was statistically significantly associated with risk of gastrointestinal diseases, especially for gastrointestinal malignancy and gastroduodenal diseases. Based on heterogeneity (P<0.05) and FPRP (P<0.2) identified in this study, we graded cumulative epidemiological evidence of an association with gastrointestinal diseases for this polymorphism. However, IL-17 (7488T/C) polymorphism (rs763780) did not show significant associations with gastrointestinal diseases either individually or overall (P>0.05). CONCLUSION: Our study provides moderate evidence that IL-17 (-197G/A) polymorphism may be a potential risk factor for gastrointestinal diseases, particularly for malignancy. Further validation of this association in a large homogeneous study is warranted.