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BACKGROUND: Chikungunya virus (CHIKV) and Dengue virus (DENV) have similar clinical symptoms, which often induce misdiagnoses. Therefore, an antigen detection diagnostic system that can clearly identify these two viruses is desirable. METHODS: In this study, we developed a novel peptide with high affinity and specificity to CHIKV, and further constructed peptide aptamer-based TRFIA assay to efficiently detect CHIKV. Peptide aptamer B2 (ITPQSSTTEAEL) and B3 (DTQGSNWI) were obtained through computer-aided design and selected as CHIKV-specific peptide aptamers based on their high binding affinity, strong hydrogen bonding, and RMSD of molecular docking. Then, a sandwich-Time-Resolved Fluoroimmunoassay (TRFIA) was successfully constructed for the detection of the interaction between peptide aptamers and viruses. RESULTS: When using B2 as the detection element, highly specific detection of CHIKV E2 was achieved with detection limits of 8.5 ng/ml in PBS solution. Variation coefficient between inter-assay showed the disturbances received from the detection of clinical fluid specimens (including serum and urine), were also within acceptable limits. The detection limits for 10-fold dilution serum and urine were 57.8 ng/mL and 147.3 ng/mL, respectively. The fluorescent signal intensity exhibited a good linear correlation with E2 protein concentration in the range of 0-1000 ng/mL, indicating the potential for quantitative detection of E2 protein. CONCLUSIONS: These results demonstrate that the construction of peptide aptamers with high affinity and specificity provides an excellent method for rapid diagnostic element screening, and the developed peptide aptamer B2 contributed to better detection of CHIKV viral particles compared to traditional antibodies.
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Aptámeros de Péptidos , Fiebre Chikungunya , Virus Chikungunya , Dengue , Humanos , Fiebre Chikungunya/diagnóstico , Simulación del Acoplamiento Molecular , FluoroinmunoensayoRESUMEN
BACKGROUND: During laparoscopic resection for colorectal cancer, there is controversy regarding whether the left colic artery (LCA) should be preserved at its origin. AIM: To investigate the prognostic significance of preservation of the LCA in colorectal cancer surgery. METHODS: Patients were divided into two groups. The high ligation (H-L) technique (refers to ligation performed 1 cm from the beginning of the inferior mesenteric artery) group consisted of 46 patients, and the low ligation (L-L) technique (refers to ligation performed below the initiation of the LCA) group consisted of 148 patients. Operative time, blood loss, lymph nodes with tumor invasion, postoperative complications and recovery time, recurrence rate, and 5-year survival rate were compared between the two groups. RESULTS: The average number of lymph nodes detected in postoperative pathological specimens was 17.4/person in the H-L group and 15.9/person in the L-L group. There were 20 patients (43%) with positive lymph nodes (lymph node metastasis) in the H-L group and 60 patients (41%) in the L-L group. No statistical differences were found between the groups. Complications occurred in 12 cases (26%) in the H-L group and in 26 cases (18%) in the L-L group. The incidences of postoperative anastomotic complications and functional urinary complications were significantly lower in the L-L group. The 5-year survival rates in H-L and L-L groups were 81.7% and 81.6%, respectively, and relapse-free survival rates were 74.3% and 77.1%, respectively. The two groups were similar statistically. CONCLUSION: Complete mesenteric resection combined with lymph node dissection around the inferior mesenteric artery root while preserving the LCA is a beneficial surgical approach during laparoscopic resection for colorectal cancer.
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Rationale: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver that is the leading cause of cancer-related mortality worldwide. However, genetic alterations and mechanisms underlying HCC development remain unclear. Methods: Tissue specimens were used to evaluate the expression of DEAD-Box 56 (DDX56) to determine its prognostic value. Colony formation, CCK8, and EdU-labelling assays were performed to assess the effects of DDX56 on HCC proliferation. The in vivo role of DDX56 was evaluated using mouse orthotopic liver xenograft and subcutaneous xenograft tumor models. Dual-luciferase reporter, chromatin immunoprecipitation, and electrophoretic mobility shift assays were performed to examine the effect of DDX56 on the MIST1 promoter. Results: DDX56 expression in HCC tissues was elevated and this increase was strongly correlated with poor prognoses for HCC patients. Functionally, DDX56 promoted HCC cell proliferation both in vitro and in vivo, while mechanistically interacting with MECOM to promote HCC proliferation by mono-methylating H3K9 (H3K9me1) on the MIST1 promoter, leading to enhanced MIST1 transcription and subsequent regulation of the PTEN/AKT signaling pathway, which promotes HCC proliferation. More importantly, the PTEN agonist, Oroxin B (OB), blocked the DDX56-mediated PTEN-AKT signaling pathway, suggesting that treating HCC patients with OB may be beneficial as a therapeutic intervention. Furthermore, we observed that ZEB1 bound to DDX56 and transcriptionally activated DDX56, leading to HCC tumorigenesis. Conclusions: Our results indicated that the ZEB1-DDX56-MIST1 axis played a vital role in sustaining the malignant progression of HCC and identified DDX56 as a potential therapeutic target in HCC tumorigenesis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Carcinogénesis/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/genética , Transformación Celular Neoplásica/genética , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/patología , Ratones , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/genéticaRESUMEN
There is a significant difference in prognosis among different risk groups. Therefore, it is of great significance to correctly identify the risk grouping of children. Using the genomic data of neuroblastoma samples in public databases, we used GSE49710 as the training set data to calculate the feature genes of the high-risk group and non-high-risk group samples based on the random forest (RF) algorithm and artificial neural network (ANN) algorithm. The screening results of RF showed that EPS8L1, PLCD4, CHD5, NTRK1, and SLC22A4 were the feature differentially expressed genes (DEGs) of high-risk neuroblastoma. The prediction model based on gene expression data in this study showed high overall accuracy and precision in both the training set and the test set (AUC = 0.998 in GSE49710 and AUC = 0.858 in GSE73517). Kaplan-Meier plotter showed that the overall survival and progression-free survival of patients in the low-risk subgroup were significantly better than those in the high-risk subgroup [HR: 3.86 (95% CI: 2.44-6.10) and HR: 3.03 (95% CI: 2.03-4.52), respectively]. Our ANN-based model has better classification performance than the SVM-based model and XGboost-based model. Nevertheless, more convincing data sets and machine learning algorithms will be needed to build diagnostic models for individual organization types in the future.
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A problematic feature of many human cancers is a lack of understanding of mechanisms controlling organ-specific patterns of metastasis, despite recent progress in identifying many mutations and transcriptional programs shown to confer this potential. To address this gap, we developed a methodology that enables different aspects of the metastatic process to be comprehensively characterized at a clonal resolution. Our approach exploits the application of a computational pipeline to analyze and visualize clonal data obtained from transplant experiments in which a cellular DNA barcoding strategy is used to distinguish the separate clonal contributions of two or more competing cell populations. To illustrate the power of this methodology, we demonstrate its ability to discriminate the metastatic behavior in immunodeficient mice of a well-established human metastatic cancer cell line and its co-transplanted LRRC15 knockdown derivative. We also show how the use of machine learning to quantify clone-initiating cell (CIC) numbers and their subsequent metastatic progeny generated in different sites can reveal previously unknown relationships between different cellular genotypes and their initial sites of implantation with their subsequent respective dissemination patterns. These findings underscore the potential of such combined genomic and computational methodologies to identify new clonally-relevant drivers of site-specific patterns of metastasis.
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Regenerative medicine holds promise to cure radiation-induced salivary hypofunction, a chronic side effect in patients with head and neck cancers, therefore reliable preclinical models for salivary regenerative outcome will promote progress towards therapies. In this study, our objective was to develop a cone beam computed tomography-guided precision ionizing radiation-induced preclinical model of chronic hyposalivation using immunodeficient NSGSGM3 mice. Using a Schirmer's test based sialagogue-stimulated saliva flow kinetic measurement method, we demonstrated significant differences in hyposalivation specific to age, sex, precision-radiation dose over a chronic (6 months) timeline. NSG-SMG3 mice tolerated doses from 2.5 Gy up to 7.5 Gy. Interestingly, 5-7.5 Gy had similar effects on stimulated-saliva flow (â¼50% reduction in young female at 6 months after precision irradiation over sham-treated controls), however, >5 Gy led to chronic alopecia. Different groups demonstrated characteristic saliva fluctuations early on, but after 5 months all groups nearly stabilized stimulated-saliva flow with low-inter-mouse variation within each group. Further characterization revealed precision-radiation-induced glandular shrinkage, hypocellularization, gland-specific loss of functional acinar and glandular cells in all major salivary glands replicating features of human salivary hypofunction. This model will aid investigation of human cell-based salivary regenerative therapies.
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Neoplasias de Cabeza y Cuello , Xerostomía , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Lactante , Ratones , Ratones Transgénicos , Saliva , Glándulas Salivales/efectos de la radiación , Xerostomía/etiologíaRESUMEN
INTRODUCTION: Breast cancer is the most prevalent cancer and the leading cause of cancer-related death in women. Conventional open mastectomy (C-OM) is one of the most common procedures for breast cancer, which involves the removal of the nipple-areola complex and a large proportion of the breast skin, leading to poor cosmetic effect and restriction of upper extremity function. Single-port insufflation endoscopic nipple-sparing mastectomy (SIE-NSM) could conceal the incision along the wrinkles in the axilla, preserve all the breast skin and nipple-areola complex and provide a better cosmetic outcome and quality of life. This trial aims to investigate the oncological safety between SIE-NSM and C-OM in early breast cancer patients. METHODS AND ANALYSIS: This is a single centre, non-blinded, randomised controlled trial (RCT) and will be conducted at Beijing Friendship Hospital. Patients will be enrolled in the inpatient ward. Breast surgeons will notify patients who meet the inclusion and exclusion criteria with the instruction of this RCT. Patients will be randomly assigned to C-OM or SIE-NSM with a 3:1 allocation as per a computer-generated randomisation schedule. Patients will be followed-up for 12 months for analysing surgical outcomes. The primary outcome is the local recurrence rate at a 12-month follow-up. The secondary outcome is the distant metastasis rate, cosmetic satisfaction score and psychosocial well-being score after a 12-month follow-up. To ensure the accuracy of the cosmetic satisfaction score and psychosocial well-being score, the standard scale, Breast-Q score, will be applied. ETHICS AND DISSEMINATION: This study will be conducted according to the medical ethics committee of the Beijing Friendship Hospital and according to the principles of the Declaration of Helsinki. All patients will receive clear instruction of their disease and treatment plan. Informed consent will be obtained from all patients when they agree to comply with our research plan. The results will be disseminated at academic presentations and publications in peer-reviewed journals. The raw data will be confidentially stored in our electronic data capture database. Data will not be shared unless an appropriate data request is submitted after the trial completion and peer-review journal publication. TRIAL REGISTRATION NUMBER: NCT04461847.
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Neoplasias de la Mama , Insuflación , Neoplasias de la Mama/cirugía , Endoscopía , Femenino , Humanos , Mastectomía/métodos , Pezones/cirugía , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Several treatments are available for treatment of early and very early-stage Hepatocellular Carcinoma, also known as small Hepatocellular Carcinoma (SHCC). However, there is no consensus with regards to the efficacies of these methods. We aimed at identifying the most effective initial treatment strategy for SHCC through Bayesian network meta-analyses. METHODS: Studies published between January, 2010, and February, 2021 were searched in EMBASE, Cochrane Library, PubMed and Web of science databases, and conference proceedings for trials. The included studies reported the survival outcomes of very early and early Hepatocellular Carcinoma patients subjected to radiofrequency ablation (RFA), microwave ablation (MWA), surgical resection (SR), transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), minimally invasive liver surgery (MIS), stereotactic body radiotherapy (SBRT) and cryoablation (CA). Then, data were extracted from studies that met the inclusion criteria. Patient survival data were retrieved from the published Kaplan-Meier curves and pooled. A Bayesian random-effects model was used to combine direct and indirect evidence. RESULTS: A total of 2058 articles were retrieved and screened, from which 45 studies assessing the efficacies of 8 different treatments in 11,364 patients were selected. The included studies had high methodological quality. Recurrence free survival* (progression/recurrence/relapse/disease/tumor-free survival were combined and redefined as RFS*) and overall survival (OS) outcomes were highest in MIS-treated patients (HR 0·57, 95% confidence intervals [CI] 0·38-0·85; HR 0.48,95% CI 0.36-0.64, respectively), followed by SR-treated patients (HR 0.60, 95% CI 0.50-0.74; HR 0.62, 95% CI 0.55-0.72, respectively). TACE was highly efficacious (58.9%) at decreasing the rates of major complications. Similar findings were obtained through sensitivity analysis, and in most of the prognostic subgroups. CONCLUSIONS: MIS and SR exhibited the highest clinical efficacies, however, they were associated with higher rates of complications. Ablation is effective in small tumors, whereas SBRT is a relatively promising treatment option for SHCC. More well-designed, large-scale randomized controlled trials should be performed to validate our findings.
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Objective: To evaluate the influence of the abdominal incision length on the gastrointestinal function recovery post-operatively. Background: Gut motility recovers more quickly after the minimally invasive laparoscopic surgery compared than after the traditional open surgery; however, whether the minimal abdominal incision contributes to the faster gut motility recovery is controversial and lacks solid clinical evidence. Methods: A registry-based secondary cohort analysis was conducted to evaluate the association between the abdominal incision length and gut motility recovery post-operatively based on a multicenter, prospective, and observational study of the prolonged post-operative ileus (PPOI) incidence and the risk factors in the patients with the major abdominal surgery. The incision length, in the centimeters, was the exposure. The primary outcome measures were the PPOI incidence and its association with the incision length. The secondary outcome included the days to the first passage of flatus and the days to the first passage of stool. Results: Overall, 1,840 patients, including 287 (15.7%) patients with the PPOI, were recruited. The PPOI incidence was 17.6% and 13.3% in the long-incision (>18 cm) and short-incision patients ( ≤ 18 cm), respectively. The incidence of the PPOI increased by 1.1% (1.0-1.1) by each centimeter increment of the incision length after adjusting for the confounding factors. In comparison to the short-incision patients, the long-incision patients had prolonged passage of stool (4.46 vs. 4.95 days, p < 0.001). Each centimeter increment of the incision length contributed to a 2% increased risk of delay in the first bowel movement [hazard ratio (HR) 0.980 (0.967, 0.994)]. Conclusion: A long abdominal incision length independently contributed to the prolonged gut function recovery post-operatively mainly by delaying the time to the first bowel movement, but not influencing the time to first passage of flatus.
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Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Although progress has been made in diagnosis and treatment, morbidity and mortality continue to rise. Chronic liver disease and liver cirrhosis are still the most important risk factors for liver cancer. Although there are many treatments, it can only be cured by orthotopic liver transplantation (OLT) or surgical resection. And the worse the degree of differentiation, the worse the prognosis of patients with liver cancer. Then it can be considered that restoring a better state of differentiation may improve the prognosis. The differentiation treatment of liver cancer is to reverse the dedifferentiation process of hepatocytes to liver cancer cells by means of drugs, improve the differentiation state of the tumor, and restore the normal liver characteristics, so as to improve the prognosis. Understanding the mechanism of dedifferentiation of liver cancer can provide ideas for drug design. Liver enrichment of transcription factors, imbalance of signal pathway and changes of tumor microenvironment can promote the occurrence and development of liver cancer, and restoring its normal level can inhibit the malignant behavior of tumor. At present, some drugs have been proved to be effective, but more clinical data are needed to support the effectiveness and reliability of drugs. The differentiation treatment of liver cancer is expected to become an important part of the treatment of liver cancer in the future.
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Hilar cholangiocarcinoma (HC) has a poor outcome in terms of survival. Forkhead box K1 (FOXK1) dysregulation is critical in solid tumors, which serves a pivotal role in the biological characteristics, such as invasion and migration, but its expression and functions in HC are unclear. The present study investigated the clinical significance and biological functions of FOXK1 in HC. Tumor microarrays and immunohistochemistry were used to evaluate FOXK1 in HC and its expression was modulated to determine its effects on chemoresistance and tumorigenesis. FOXK1 was highly expressed in HC and cell lines, which was associated with tumor invasion, regional lymph node metastasis, tumor recurrence and poor prognosis. Silencing FOXK1 in HC cells inhibited invasion and migration, upregulated E-cadherin, and downregulated vimentin, matrix metallopeptidase 9 and Twist in HC cells. Sensitivity to 5-fluorouracil and cisplatin was increased, and glutathione S-transferase π, multidrug resistance mutation 1 and P-glycoprotein expression levels were downregulated in RBE cells in vitro following FOXK1 knockdown. These results indicated that FOXK1 plays an oncogenic role in HC progression and can serve as a novel therapeutic target for HC.
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Neoplasias de los Conductos Biliares/metabolismo , Factores de Transcripción Forkhead/metabolismo , Tumor de Klatskin/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Adulto , Anciano , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Línea Celular Tumoral , Femenino , Factores de Transcripción Forkhead/genética , Humanos , Tumor de Klatskin/genética , Tumor de Klatskin/patología , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas/genéticaRESUMEN
OBJECTIVE: Anastomotic leakage (AL) is a frequent complication after laparoscopic rectal cancer resection (LRCR). The main objective of the present study was to identify accurate indicators of AL after LRCR. METHODS: A retrospective case-control study was performed of 185 patients who underwent laparoscopic surgery for rectal cancer between March 2012 and February 2017 at Beijing Friendship Hospital. Potential indicators of AL were examined via univariate and multivariate analyses. The performance of multivariate analysis was evaluated using receiver operating characteristic (ROC) curves. RESULTS: The overall AL rate was 17.84%. Multivariate analysis identified drainage smell (odds ratio [OR = 35.318, 95% confidence interval [CI] = 7.114 to 175.338) and peritonitis [OR = 17.475, 95% CI = 1.540 to 198.318) as independent indicators of AL. The area under the ROC curve was 0.720 (95% CI = 0.606 to 0.835). CONCLUSION: Drainage smell and peritonitis could be reliable and accurate indicators of AL after LRCR.
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Laparoscopía , Peritonitis , Neoplasias del Recto , Fuga Anastomótica/diagnóstico , Fuga Anastomótica/etiología , Estudios de Casos y Controles , Drenaje , Humanos , Laparoscopía/efectos adversos , Peritonitis/etiología , Peritonitis/cirugía , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Factores de Riesgo , OlfatoRESUMEN
OBJECTIVE: This study was performed to identify risk factors for anastomotic leakage (AL) and combine these factors to create a prediction model for the risk of AL after laparoscopic rectal cancer resection. METHODS: This retrospective study involved 185 patients with rectal cancer who underwent laparoscopic resection from March 2012 to February 2017. Five risk factors were analyzed by multivariate analysis. A prediction model was established by combining the risk factors from the multivariate analysis, and the accuracy of the model was evaluated by a receiver operating characteristic curve. RESULTS: The overall AL rate was 17.84%. The multivariate analysis identified the following independent risk factors for AL: high body mass index (odds ratio [OR], 3.009; 95% confidence interval [CI], 1.127-7.125), preoperative radiochemotherapy (OR, 3.778; 95% CI, 1.168-12.219), larger tumor size (OR, 2.710; 95% CI, 1.119-6.562), and longer surgical time (OR, 2.476; 95% CI, 1.033-5.932). We established a prediction model that can evaluate the risk of AL by determining the predictive probability. The area under the curve for the model's predictive performance was 0.70 (95% CI, 0.598-0.795). CONCLUSION: A prediction model was created to predict the risk of AL after laparoscopic rectal cancer resection.
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Laparoscopía , Neoplasias del Recto , Fuga Anastomótica/etiología , Humanos , Laparoscopía/efectos adversos , Neoplasias del Recto/cirugía , Recto , Estudios Retrospectivos , Factores de RiesgoRESUMEN
RATIONALE: Complete small intestinal volvulus is a rare entity in adults, unlike partial intestinal volvulus. Although prompt surgical intervention is the mainstay of treatment, attention should also be paid to recovery of intestinal function postoperatively. Ignoring this issue during the postoperative recovery process can have serious consequences. We report the case of an 82-year-old woman with complete small intestinal volvulus at the root of the superior mesenteric vessel. PATIENTS CONCERNS: The patient was admitted for acute onset (22âhours) of abdominal pain and distention. Nausea and vomiting also developed during this period. DIAGNOSES: Abdominal physical examination was suspicious for peritoneal irritation. Computed tomography scan showed anticlockwise swirl of the mesenteric vessels at the lower margin of the pancreas with distension of the entire small intestine. A complete small intestinal volvulus was diagnosed. INTERVENTIONS: Laparotomy and detorsion of the volvulus were performed after early diagnosis. OUTCOMES: The patient developed intestinal wall edema because of ischemic-reperfusion damage. She exhibited severe abdominal distention and absent intestinal motility. Two days later, she went into septic shock; she died 19 days after surgical intervention. LESSONS: Because complete small intestinal volvulus involves the entire intestine, ischemic-reperfusion intestinal damage after detorsion may be severe and can predict prognosis.
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Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Motilidad Gastrointestinal , Vólvulo Intestinal/cirugía , Complicaciones Posoperatorias , Choque Séptico , Anciano de 80 o más Años , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Resultado Fatal , Femenino , Humanos , Vólvulo Intestinal/diagnóstico , Vólvulo Intestinal/fisiopatología , Intestino Delgado/fisiopatología , Intestino Delgado/cirugía , Laparotomía/efectos adversos , Laparotomía/métodos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/fisiopatología , Choque Séptico/diagnóstico , Choque Séptico/etiologíaRESUMEN
Uranium can be immobilized as nanoscale minerals by biomineralization under aerobic conditions. Current researches on nonreductive biomineralization of U(VI) mainly focus on revealing the mechanisms associated with functional groups and enzymes. However, studies on the effect of initial uranium concentration on the uranium bio-immobilization are relatively rare. This paper researched the immobilization of U(VI) at different concentrations by Bacillus cereus 12-2. Adsorption experiments showed that the adsorption equilibrium was rapidly reached within 10 min when U(VI) concentration was 25 mg/L while over 2 h when U(VI) concentration was 200 mg/L. The biological adsorption capacity improved gradually from 24.68 to 163.17 mg/g (dry weight) as U(VI) concentration increased, but the removal rate of uranium decreased from about 100% to 80%. X-ray diffraction (XRD) showed that nanoscale uramphite ((NH4)(UO2)PO4·3H2O) formation time was 4, 4, 12 and 24 h, respectively when initial U(VI) concentration was 25, 50, 75 and 100 mg/L. No mineral was formed after reaction for 24 h when U(VI) concentration was 200 mg/L. Uramphite had better peaks in spectrum after 50 mg/L U(VI) had interacted with Bacillus cereus 12-2 for 4 h. XRD, SEM (scanning electron microscopy) and TEM (transmission electron microscopy) indicated that a large number of amorphous uranium-containing particles appeared extracellularly after 10 min and nanoscale uramphite formed intracellularly after 4 h when uranium concentration was 50 mg/L. This study showed that the time required for adsorption equilibrium and mineralization by Bacillus cereus 12-2 was shorter when the initial U(VI) concentration was lower within a certain range. This phenomenon could be attributed to the increase of relative content of functional groups and the decrease of cytotoxicity of uranium at low concentrations. This work had certain guiding significance for further understanding the mechanism of uranium biomineralization and the application of Bacillus cereus 12-2 under actual uranium-contaminated environments.
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Uranio , Adsorción , Bacillus cereus , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Rastreo , Difracción de Rayos XRESUMEN
BACKGROUND/AIM: Although the advent of Helicobacter pylori eradication and global societal changes are widely assumed to impact on gastric cancer (GC)-related mortality, there is remarkable little quantitative and qualitative insight into the nature of its effects. Here, we exploited a nationwide reporting system to investigate the epidemiological features of GC-related mortality in China between 2006 and 2013. PATIENTS AND METHODS: GC mortality data between 2006 and 2013 were obtained from the National Disease Surveillance System published by the China Center for Disease Control and Prevention (CDC). RESULTS: GC mortality increased by 8.2% (from 18.87/100,000 to 20.41/100,000), while GC mortality standardized by the age scale of the population in 2010 decreased by 17.8% (from 21.87/100,000 to 17.98/100,000). Standardized GC mortality in males (25.66/100,000 to 33.89/100,000) was higher compared to females (10.72/100,000 to 14.79/100,000), while standardized GC mortality in rural areas (19.17/100,000 to 26.46/100,000) was higher than in urban areas (15.48/100,000 to 20.04/100,000). Both crude and standardized rates in the 0- to 29-year-old group increased by 22.3% and 16.2%, respectively; while these rates declined in the 30- to 59-year-old group and over 60-year-old group. The proportion of GC deaths that accounts for all cancer deaths declined from 15.99% (2006) to 13.6% (2013); however, the proportion in the 0- to 29-year-old group revealed an increasing trend from 2006 (3.20%) to 2013 (3.87%). CONCLUSION: Our results reveal a remarkable increase in GC-related mortality in subjects under the age of 30 calling for further measures to prevent the increase in the incidence of GC in young patients.
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Vigilancia de la Población , Neoplasias Gástricas/mortalidad , Factores de Edad , China/epidemiología , Femenino , Humanos , Incidencia , Masculino , Sistema de Registros , Factores de Riesgo , Población Rural , Factores Sexuales , Población UrbanaRESUMEN
BACKGROUND AND AIM: Adjuvant chemotherapy is an important component in the treatment of gastric cancer (GC) patients; however, some patients do not respond to the drugs. We aimed to develop a practical profile based on serum microRNAs (miRNAs) that can be used to predict patients likely to respond to treatment. METHODS: Microarrays were used to screen cisplatin-resistant SGC7901/DDP GC cells and the parental SGC7901 cell lines for miRNAs related to chemotherapy sensitivity. The correlation between the expression patterns of identified serum miRNAs and overall survival was confirmed in 68 GC patients. Furthermore, we also validated the signature of the serum miRNAs in an independent cohort of 50 GC patients. RESULTS: From the screening microarrays, we focused on miR-15a, miR-15b and miR-93 as downregulated miRNAs in the SGC7901/DDP cells and miR-27a, miR-106a and miR-664 as upregulated miRNAs. Only serum miR-106, miR-15a, miR-93 and miR-664 were useful in predicting the prognosis of patients who received adjuvant chemotherapy. We identified a signature of four serum miRNAs (miR-106, miR-15a, miR-93 and miR-664) that, when combined, can be used as a risk score for overall survival. Patients with a higher risk score had worse prognosis (p < 0.05). For the independent cohort of patients, the signature of the four miRNAs predicted prognosis well. CONCLUSION: Our data showed that the risk score derived from the four serum miRNAs was closely associated with the overall survival in GC patients who received adjuvant chemotherapy.
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Antineoplásicos/uso terapéutico , Cisplatino/uso terapéutico , Perfilación de la Expresión Génica , MicroARNs/sangre , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Anciano , Línea Celular Tumoral , Quimioterapia Adyuvante , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias Gástricas/metabolismoRESUMEN
As several epidemiological studies on the association of coffee consumption with gastric cancer risk have produced inconsistent results, this meta-analysis was designed to synthesize current evidence of this potential relationship. We searched PubMed, EMBASE, and the Cochrane Library up to September 2014 to retrieve relevant articles. Prospective cohort studies were included if the relative risks (RRs) or hazard ratios and 95% confidence intervals (CIs) for gastric cancer according to coffee consumption were reported. Fixed- or random-effects models were used based on heterogeneity. The search yielded 13 eligible cohort studies of 3484 incident gastric cancer patients from among 1,324,559 participants. A significantly increased risk was found between gastric cardia cancer and coffee consumption (RR = 1.50, 95% CI: 1.09-2.07). Compared with Europeans (RR = 1.12, 95% CI: 0.86-1.46) and Asians (RR = 0.96, 95% CI: 0.72-1.27), Americans (RR = 1.36, 95% CI: 1.06-1.74) demonstrated a significantly positive association. However, the significant differences of the pooled results vanished after adjusting for smoking or body mass index. Our meta-analysis results suggest that a high level of coffee consumption is a risk factor for gastric cancer. However, these results should not be overinterpreted because residual confounding effects of other factors could exist.
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Café/efectos adversos , Neoplasias Gástricas/etiología , Estudios de Cohortes , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Humanos , Estudios Prospectivos , Sesgo de Publicación , Factores de RiesgoRESUMEN
OBJECTIVE: MicroRNAs (miRNAs) have potential as diagnostic biomarkers in cancer. Evaluation of the association between miRNA expression patterns and early detection of liver metastasis in colorectal cancer (CRC) has not been reported. METHODS: We investigated the expression of metastasis-associated miRs-31, 335, 206, 141, 126, 200b, 200c, 21, Let7a, Let7b and Let7c in localized, liver-metastatic and other organ-metastatic CRC (OM-CRC). Expressions of target miRNAs in serum were evaluated in 116 consecutive localized CRC (L-CRC), 72 synchronous liver-metastatic CRC (SLM-CRC) and 36 other OM-CRC by quantitative real-time PCR. RESULTS: Seven of 11 tested miRNAs could be detected from serum. Four miRNAs, miR-126, Let-7a, miR-141 and miR-21 were identified as metastasis-associated miRNAs. Compared with L-CRC, significant up-regulated expression was observed for miR-141 and miR-21 in SLM-CRC and OM-CRC, down-regulated expression was observed for miR-126 in SLM-CRC and OM-CRC, and up-regulated expression of Let-7a in OM-CRC. The receiver operating characteristic (ROC) curve showed serum miR-126 had a cut-off [log10 relative quantity (log10 (RQ))=-0.2005] with 77.78% sensitivity and 68.97% specificity with an area under curve (AUC) of 0.7564, miR-141 had a cut-off (log10 (RQ)=-0.2285) with 86.11% sensitivity and 76.11% specificity with an AUC of 0.8279, and miR-21 had a cut-off (log10 (RQ)=-0.1310) with 73.61% sensitivity and 66.38% specificity with an AUC of 0.7479. CONCLUSIONS: We identified liver metastasis-associated miRNAs, suggesting serum miR-126, miR-141 and miR-21 may be novel biomarkers for clinical diagnosis of early stage liver-metastatic CRC.
RESUMEN
OBJECTIVE: Gastric cancer is a genetically heterogeneous disease that progresses via different oncogenes. MicroRNA (miRNA) can regulate oncogene expression at the post-translational level. In this review, we summarize the most commonly altered miRNAs and their possible roles in cancer initiation and progression in gastric cancer. DATA SOURCES: Most articles were identified by searching PubMed online resources using the key terms of microRNA and gastric cancer. STUDY SELECTION: Mainly original milestone articles and critical reviews written by major pioneer investigators in the field were selected, and the 69 most important articles were cited finally. RESULTS: A set of miRNAs are consistently deregulated in gastric cancer, although there is no clear miRNA expression profiles, such as miR-21 and miR-17 (â¼92 clusters). These deregulated miRNAs play important roles in promoting cell proliferation, tumor metastasis, and chemotherapeutic resistance in gastric cancer by targeting different oncogenes. Clinical relevance of these deregulated miRNAs is proved to be associated with TNM stages, metastasis, and prognosis of gastric cancer patients. In addition, circulating miRNAs are promising noninvasive biomarkers for gastric cancer. CONCLUSIONS: miRNAs have produced a novel paradigm in research in gastric cancer. These small molecules play macroroles in gastric cancer initiation and progression. These results will help us improve management of gastric cancer in future.