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In order to meet the requirements of tertiary oil recovery technology in a low-permeability, dense, and high-salt reservoir, gaseous SiO2 nanoparticles were modified with trichloro(octyl)silane and aminopropyl triethoxysilane by interface protection modification, and amphiphilic Janus-SiO2 nanoparticles with hydrophobic carbon chain and hydrophilic amino group were prepared. The basic properties of amphiphilic nanoparticle dispersion were evaluated by surface interfacial tension and wettability tests, and the oil displacement effect of amphiphilic nanoparticle dispersion was investigated. The results show that the size distribution of Janus-SiO2 nanoparticles with n-octyl as the hydrophobic carbon chain and amino group as the hydrophilic headgroup is uniform, and they have good dispersion in mineralized water. The change of salinity has little effect on the interfacial activity. The interfacial tension between the amphiphilic nanoparticle dispersion and crude oil is always on the order of 10-2 mN/m, and the amphiphilic nanoparticle dispersion has good interfacial activity. Amphiphilic nanoparticles adsorbed on the rock surface can enhance the hydrophilicity of the rock surface. Amphiphilic nanoparticle dispersion liquid has a certain effect of improving oil recovery in the environment of high-salt and low-permeability reservoir. Under the condition of 65 °C and salinity of 8000 mg/L, injection of 0.5 PV 0.05% amphiphilic nanoparticle dispersion can enhance oil recovery by 14.6% on the basis of water flooding. The mechanism of amphiphilic nanoparticles to improve the recovery efficiency of low-permeability tight high-salt reservoir mainly includes reducing the oil-water interfacial tension, changing the rock wettability, and enhancing the shear viscosity of oil and water interface and the interfacial film strength, which has excellent potential application prospect in the development of low-permeability tight high-salt reservoir.
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CO2 flooding has been successfully used in numerous oil fields as a strategy to improve oil recovery. However, several issues, including gas channeling, profile control, CO2 sweep efficiency, oil displacement efficiency, etc., have been revealed in the development of CO2 flooding, particularly in a fractured reservoir. In this paper, in view of the focus issues, a novel multistage plugging system is investigated, mainly including the polymer-gel system. The static and dynamic polymer-gel system performances are comprehensively evaluated. Based on the features of a fractured reservoir, a multiscale fracture model is built, and the applicable limits of the polymer-gel system are proposed. When the fracture width is greater than 0.65 mm, the plugging effect of the polymer gel becomes worse. However, the plugging effect is clearly strengthened by the use of polymer gel, foam, and bulk particles, which also significantly improves the injection-production profile. The experimental results show that CO2 flooding could increase the ultimate recovery by 7.67%.
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Produced gas re-injection is an effective and eco-friendly approach for enhancing oil recovery from shale oil reservoirs. However, the interactions between different gas phase components, and the oil phase and rocks are still unclear during the re-injection process. This study aims to investigate the potential of produced gas re-injection, particularly focusing on the effects of methane (CH4) content in the produced gas on shale oil displacement. Molecular dynamics simulations were employed to analyze the interactions between gas, oil, and matrix phases with different CH4 proportions (0%, 25%, 50%, and 100%), alkanes and under various burial depth. Results show that a 25% CH4 content in the produced gas achieves almost the same displacement effect as pure carbon dioxide (CO2) injection. However, when the CH4 content increases to 50% and 100%, the interaction between gas and quartz becomes insufficient to effectively isolate oil from quartz, causing only expansion and slight dispersion. Interestingly, the presence of CH4 has a synergistic effect on CO2, facilitating the diffusion of CO2 into the oil film. During the gas stripping process, CO2 is the main factor separating oil from quartz, while CH4 mainly contributes to oil expansion. In addition, for crude oil containing a large amount of light alkanes, extracting light components through mixed gas may be more effective than pure CO2. This study offers valuable insights for applications of produced gas re-injection to promote shale oil recovery.
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Due to the small pore throat characteristics of tight oil reservoirs, their strong capillary pressure makes imbibition replacement an effective development method. Field data has indicated that only a little fracture fluid can flow back and that there is an enhancement in oil recovery with shut-in periods after volume fracturing. A large number of scholars have carried out core-scale experiments on imbibition characteristics, but there has been limited research on the quantitative characterization of the differential pressure and imbibition replacement during counter-current imbibition. At the same time, there was also controversy on the calculation method of the optimal soaking time. In this paper, a mathematical model of oil-water two-phase flow is first established. Then, a mathematical model representing differential pressure and imbibition replacement in tight reservoirs is derived with a diversion function. Based on the saturation equation, Corey relative-permeability curve, and J function, the model is simplified to a mathematical model of spontaneous imbibition in the shut-in periods after volume fracturing. Second, based on the finite difference method, a dynamic solution method for the flow field considering the dynamic capillary force was established, and the variation law of the pressure field and the water saturation field during the soaking time was revealed. The simulation results show that imbibition characteristics are the core of flow field reconstruction, and the differential pressure action can ensure the advancing distance of the fracturing fluid; both of them are not a linear superposition on tight oil development but complement each other and promote each other. Third, according to the growth rate of the imbibition replacement between fractures and the matrix during the soaking time, the calculation method of optimal soaking time was established. Taking the development parameters of the volume fracturing development case in the Ordos Basin into account, a reasonable soaking time was optimized. Finally, we analyzed the optimal soaking time under different conditions, and a chart of optimal soaking time for different initializations was plotted. Such a chart has profound reference significance for engineers, and they can make quick and accurate decisions regarding development and adjustment.
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Prediabetes is a transitional state between normal blood glucose levels and diabetes, but it is also a reversible process. At the same time, as one of the most important tissues in the human body, the metabolic disorder of skeletal muscle is closely related to prediabetes. Huidouba (HDB) is a clinically proven traditional Chinese medicine with significant effects in regulating disorders of glucose and lipid metabolism. Our study aimed to investigate the efficacy and mechanism of HDB in prediabetic model mice from the perspective of skeletal muscle. C57BL/6J mice (6 weeks old) were fed a high-fat diet (HFD) for 12 weeks to replicate the prediabetic model. Three concentrations of HDB were treated with metformin as a positive control. After administration, fasting blood glucose was measured as an indicator of glucose metabolism, as well as lipid metabolism indicators such as total triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), free fatty acid (FFA), and lactate dehydrogenase (LDH). Muscle fat accumulation and glycogen accumulation were observed. The protein expression levels of p-AMPK, AMPK, PGC-1α, PPAR-α, and GLUT-4 were detected. After HDB treatment, fasting blood glucose was significantly improved, and TG, LDL-C, FFA, and LDH in serum and lipid accumulation in muscle tissue were significantly reduced. In addition, HDB significantly upregulated the expression levels of p-AMPK/AMPK, PGC-1α, PPAR-α, and GLUT-4 in muscle tissue. In conclusion, HDB can alleviate the symptoms of prediabetic model mice by promoting the AMPK/PGC-1α/PPARα pathway and upregulating the expression of GLUT-4 protein.
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CO2 injection and water alternating gas (WAG) injection are crucial to improve the oil recovery method and have optimized development in numerous oil fields. Many issues, such as gas channeling, water clogging, and a shortage of gas injection capacity, are addressed in the studies. Considering these conflicts, we suggest in this work a unique method of surfactant alternating gas (SAG) injection. Additionally, axisymmetric drop shape analysis and other approaches are utilized to explore the interface properties of a variety of systems, including CO2/carbonated water/water/surfactant/oil systems. SAG injection combines the advantages of surfactant and WAG injection. Although CO2 molecules have an effect on surfactant aggregation at the oil-water interface in the SAG system, carbonated water has little effect on surfactant performance in lowering oil-water interface tension. Pilot studies reveal that a SAG ratio of 3:2 at 74 °C and 0.5 wt% concentration significantly improves oil recovery.
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Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.
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Mastitis Granulomatosa , Mama/patología , Consenso , Femenino , Mastitis Granulomatosa/diagnóstico , Mastitis Granulomatosa/patología , Mastitis Granulomatosa/terapia , Humanos , RecurrenciaRESUMEN
Chemical flooding technology has been widely applied in medium- and high-permeability reservoirs. However, it is rarely applied in low-permeability reservoirs, which is mainly limited by reservoir physical properties, chemical agents, injection capacity, and so forth. In this paper, a novel chemical formula used in low-permeability reservoirs was developed. In response to the low-permeability reservoir geological characteristics, fluid properties, and water flooding development of the target block, some experimental studies and field project studies of polymer-surfactant flooding were carried out. The surfactant structure and polymer molecular weight were determined from laboratory experiments. The polymer-surfactant binary system was synthesized. It had good injectivity in low-permeability reservoirs, and its oil recovery efficiency increased over 10% in the laboratory experiment. The result was higher than that of single chemical flooding. After field implementation, initial results have been achieved with an increase in injection pressure. The chemical formula can effectively alleviate intra-layer and inter-layer contradictions in the reservoir. The project has increased oil output by 77,700 t and the recovery factor by 3.5%. The experience and lessons were of great significance for the development of chemical flooding in high-temperature, high-salinity, and low-permeability reservoirs.
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We studied the lipid-regulating effect and molecular mechanism of the medical components of Alisma orientalis: alisol A, alisol B, 23-acetyl alisol C (23C) and the 3 (alisol A): 1(alisol B):1(23C) and 2(alisol A):2(alisol B):1(23C) mixtures designed based on the ratio of them in Alisma orientalis from Fujian, Guangxi Province, China. The animal experiment and network pharmacology showed that ACAT was one of its lipid-regulating targets and alisols may reduce the level of TC by inhibiting ACAT activity. The molecular simulation and homologous modeling results suggested that the binding of alisol mixtures with ACAT was stronger than that of monomers because alisol monomers acted on different active regions of ACAT resulting in the superposition effect and caused the synergistic effect. The lipid-regulating effect of Fujian mixture was stronger than that of Guangxi mixture showing that 3:1:1 was a better ratio. The N-terminal lipid-regulating activity of ACAT was stronger than that of transmembrane domain 1.
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INTRODUCTION: Lonicera japonica Thunb. is an economically important species of honeysuckle belonging to the Caprifoliaceae family. All aerial parts of L. japonica (leaf, flower bud, flower, and caulis) are used as herbal remedies in traditional Chinese medicine. The application of plant metabolomics to the study of L. japonica provides the potential for identifying the phytochemical composition and useful chemical markers of the plant. OBJECTIVE: To develop a strategy integrating metabolic profiling and partial least squares discriminant analysis (PLS-DA) to separate the aerial parts of L. japonica based on the occurrence of chemical markers. METHODOLOGY: The two-part strategy consisted of (1) ultra-fast liquid chromatography coupled with triple quadrupole-time of flight tandem mass spectrometry (UFLC-triple TOF-MS/MS), (2) PLS-DA, which was applied to distinguish between the different aerial parts and reveal their differential characteristic metabolites. RESULTS: A total of 71 metabolites were identified from samples, and eight candidate compounds were identified (lonicerin, kaempferol-3-O-rutinoside, loganin, isochlorogenic acid B, isochlorogenic acid C, secologanic acid, luteoloside, astragalin) as optimal chemical markers based on variable importance in projection (VIP) and p-value. The relative contents of eight candidate compounds were compared based on their peak intensities. CONCLUSION: This study established an efficient strategy for exploring metabolite profiling and defining chemical markers among the different aerial parts of L. japonica, and laid the foundation for elucidating the phytochemical differences in efficacy between Lonicerae Japonicae Flos (LJF) and Lonicerae Japonicae Caulis (LJC). Our findings also indicate that the leaves of L. japonica leaf could be used as an alternative medicinal resource for LJF and provide a reference for comprehensive exploitation and utilisation of L. japonica resources.
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Lonicera , Cromatografía Líquida de Alta Presión , Análisis Discriminante , Análisis de los Mínimos Cuadrados , Espectrometría de Masas en TándemRESUMEN
OBJECTIVE: Despite of previous report regarding the aberrant overexpression of hsa_circ_0011290 in thyroid cancer, the regulatory mechanism and mechanistic involvements of which were still elusive currently in papillary thyroid cancer (PTC). Here we set out to characterize expression status and functional contributions of hsa_circ_0011290 in this disease especially through mode-of-action of sponging RNA. METHODS: Relative expression of hsa_circ_0011290, microRNA (miR)-1252 and FSTL1 was quantified by real-time polymerase chain reaction. Glucose metabolism was determined by examination of glucose uptake, lactate production and ATP contents. The regulatory effects of miR-1252 on both hsa_circ_0011290 and Follistatin Like 1 (FSTL1) were interrogated by luciferase reporter assay. Direct binding between miR-1252 with hsa_circ_0011290 and FSTL1 transcripts were analyzed by RNA pulldown assay. Protein levels of FSTL1 was examined by Western blots. RESULTS: Aberrant over-expression of hsa_circ_0011290 was associated with advanced stage and unfavorable prognosis of PTC. Knockdown of hsa_circ_0011290 greatly inhibited cell viability, proliferation and stimulated cell apoptosis in PTC cells. Meanwhile, glucose metabolism was significantly switched with decreased glucose uptake and lactate production, and increased ATP contents. We identified miR-1252 as target miR of hsa_circ_0011290, and miR-1252 evidently inhibited expressions of both luciferase reporter and endogenous hsa_circ_0011290, and miR-1252 was negatively regulated by hsa_circ_0011290 vice versa. We further suggested that FSTL1 as direct target of miR-1252, and provided direct evidences in support of binding between miR-1252 with both hsa_circ_0011290 and FSTL1. Through sponging miR-1252, hsa_circ_0011290 was capable of positively modulate FSTL1 expression. Notably, inhibition of miR-1252 completely reversed phenotypic effects of hsa_circ_0011290 knockdown including cell viability, proliferation, apoptosis and glucose metabolisms. CONCLUSION: Our study uncovered the oncogenic contributions of hsa_circ_0011290-miR-1252-FSTL1 in PTCs.
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Apoptosis/fisiología , Proliferación Celular/fisiología , ARN Circular/metabolismo , Transducción de Señal/fisiología , Cáncer Papilar Tiroideo/metabolismo , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Proteínas Relacionadas con la Folistatina/metabolismo , Técnicas de Silenciamiento del Gen , Glucólisis/fisiología , Humanos , MicroARNs/metabolismo , Pronóstico , ARN Circular/análisis , ARN Circular/genética , Transducción de Señal/genética , Cáncer Papilar Tiroideo/diagnósticoRESUMEN
We prepared extracts of Alisma orientalis from Sichuan and Fujian Province, China. Based on the ratio of alisol B 23-acetate (23B) to alisol A 24-acetate (24A) in two Alisma orientalis extracts, we prepared two mixtures of 24A and 23B (24A:23B = 1:3 or 1:10). The antitumor molecular mechanism of the monomers 24A and 23B, the two mixtures and the effective components of Alisma orientalis from different habitats were studied. The MTT assay suggested that the difference in the antitumor activity of Alisma orientalis from different habitats was correlated to the ratio of 24A to 23B. The multi-spectroscopic analysis suggested that the effective components, the monomers and mixtures interacted with c-myc DNA in a partial intercalation manner. The binding strength of the alisol acetates to c-myc DNA was consistent with the anticancer activity, indicating that c-myc DNA was the anticancer target. The molecular simulation indicated that the mixtures were all directly bound to different base pairs of c-myc DNA for a superimposed effect, which led to the binding strength of the mixtures to c-myc DNA was stronger than that of the monomers. The molecules in the 1:3 mixture were all bound to different base pairs of c-myc DNA. However, for the 1:10 mixture, seven molecules of 23B bound to the side chain of 24A, resulting in the mixture with a long chain structure which increased the steric hindrance of 24A. As a result, affinity between 24A and c-myc DNA in the 1:10 mixture was weaker than that in the 1:3 mixture. [Formula: see text] The antitumor molecular mechanism of the alisol monomers 24A and 23B, the mixtures with different proportions and the effective components of Alisma orientalis from different habitats were studied. The order of the antitumor activity was as follows: Sichuan > Fujian, 24A-23B (1:3) > 24A-23B (1:10) > 23B > 24A. The antitumor activity of Alisma orientalis from different habitats was consistent with the mixtures which were designed according to the contents of the active ingredients of the medicinal materials, indicating that the antitumor activity of Alisma orientalis from Sichuan is better than that from Fujian which is related to the contents of 24A and 23B and the proportion of 1:3 is better than 1:10. The binding strength of the mixtures to c-myc DNA was consistent with the anticancer activity. The mixtures were all directly bound to different base pairs of c-myc DNA for a superimposed effect, which led to the strength of the interaction of the mixtures to c-myc DNA was stronger than that of the monomers. For the 24A-23B (1:3) mixture, the four small molecules bound to c-myc DNA directly and interacted with different base pairs of c-myc DNA. While for the 24A-23B (1:10) mixture, 24A and three 23B molecules interacted with c-myc DNA, the remaining seven 23B molecules bound to the side chain of 24A, which increased the steric hindrance. The binding of the mixture to c-myc DNA was decreased. Communicated by Ramaswamy H. Sarma.
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Alisma , ADN/genética , Extractos VegetalesRESUMEN
BACKGROUND: The association between obesity and depression has been documented in previous systematic studies but remains controversial. Many prospective studies have focused on children and youth, and several studies have examined this relationship among older populations. This study of the changes in obesity status aimed to examine the association between depression and obesity among middle-aged and elderly adults in China. METHODS: The data originated from the follow-up survey (2011 and 2013-2015) of the China Health and Retirement Longitudinal Study (CHARLS) and included 3337 residents aged at least 45 years who completed a physical examination and were evaluated with the Center for Epidemiological Studies Depression Scale (CES-D-10), which assessed depressive symptoms. Obesity status was defined by body mass index (BMI) and waist circumference (WC) according to Chinese criteria. A time-dependent Cox proportional hazards model was used to estimate the relationship between obesity status and depressive symptoms. RESULTS: The rate of depression in men and women was 26.67 and 38.37%, respectively. Based on BMI, the proportion of the population that was overweight and obese was 28.07 and 9.26%, respectively, in males and 35.03 and 16.84%, respectively, in females. Males with obesity were less likely to suffer from depressive symptoms than males with a normal weight (ORHR = 0.506, 95% CI = 0.347~ 0.736). Based on WC, the proportion of abdominal obesity was 49.35% in males and 73.65% in females. Males with abdominal obesity were less likely to suffer from depressive symptoms than males without abdominal obesity (ORHR = 0.775, 95% CI = 0.644~ 0.933). CONCLUSION: Obesity is more likely to be associated with the onset of depression in males than in females. However, regardless of underweight or overweight status, the relationship between weight and depressive symptoms is negatively associated among females and males. In conclusion, both BMI and WC can be used as tools for examining the association between obesity and depression.
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Índice de Masa Corporal , Depresión/epidemiología , Obesidad/epidemiología , Circunferencia de la Cintura , Anciano , Pueblo Asiatico , China/epidemiología , Estudios de Cohortes , Depresión/complicaciones , Trastorno Depresivo/complicaciones , Trastorno Depresivo/epidemiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad Abdominal/complicaciones , Obesidad Abdominal/epidemiología , Sobrepeso , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Jubilación/psicología , Factores Sexuales , Encuestas y Cuestionarios , DelgadezRESUMEN
HUWE1 (the HECT, UBA, and WWE domain-containing protein 1) is an ubiquitin E3 ligase which plays an important role in coordinating diverse cellular processes. It has been found to be dysregulated in various cancer type and its functions in tumorigenesis remain controversial. The potential tumour suppressive role of HUWE1 in thyroid cancer development was investigated by knocking down HUWE1 in three authentic thyroid cancer cell lines, WRO, FTC133 and BCPAP, followed by various functional assays, including cell proliferation, scratch wound healing and invasion assays. Xenograft experiment was performed to examine in vivo tumour suppressive properties of HUWE1. Small-interfering RNA mediated knockdown of HUWE1 promoted cell proliferation, cell migration and invasion in thyroid cancer cells. Overexpression of HUWE1 conferred partial sensitivity to chemo drugs interfering with DNA replication in these cells. Moreover, HUWE1 was found to be down-regulated in human thyroid cancer tissues compared with matched normal thyroid tissues. In addition, overexpression of HUWE1 significantly inhibited tumour growth in vivo using xenograft mouse models. Mechanistic investigation revealed that HUWE1 can regulate p53 protein level through its stabilization. HUWE1 functions as a tumour suppressor in thyroid cancer progression, which may represent a novel therapeutic target for prevention or intervention of thyroid cancer.
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Biomarcadores de Tumor/biosíntesis , Carcinogénesis/genética , Neoplasias de la Tiroides/genética , Proteína p53 Supresora de Tumor/genética , Ubiquitina-Proteína Ligasas/biosíntesis , Animales , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Ratones , Invasividad Neoplásica/genética , Neoplasias de la Tiroides/patología , Proteínas Supresoras de Tumor , Ubiquitina-Proteína Ligasas/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Vascular adhesion protein-1 (VAP-1) is a glycoprotein that mediates tissue-selective lymphocyte adhesion. The prognostic value of VAP-1 has been determined in gastric cancer. The aim of this study was to evaluate the changes and the predictive value of serum VAP-1 in patients with thyroid cancer. A total of 126 patients with thyroid nodules and 53 healthy controls participated in this study. The patients were further divided into subgroup 1 (69 cases with benign thyroid nodules) and subgroup 2 (57 cases with thyroid cancer). Serum VAP-1 was measured by time-resolved immunofluorometric assay. Diagnostic value of presurgical VAP-1 for thyroid cancer was conducted by receiver operating characteristic (ROC) curves. Serum levels of VAP-1 were significantly lower in thyroid cancer group than in healthy control and benign thyroid nodule groups. VAP-1 concentrations negatively correlated with serum thyroglobulin (Tg) levels in thyroid cancer patients (r = -0.81; p < 0.001). The optimum cut-off value of VAP-1 was 456.6 ng/mL with a 77.4% specificity and 66.7% sensitivity for thyroid cancer diagnosis. Serum VAP-1 decreased in thyroid cancer patients and VAP-1 could be a potential useful adjunct biomarker in the diagnosis of thyroid cancer.
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Burkitt lymphoma is a fast growing non-Hodgkin lymphoma that occurs primarily in young males. The causes of Burkitt lymphoma include chromosome rearrangement and virus infection, but accurate and complete reasons remain to be discovered. The available treatment for Burkitt lymphoma is chemotherapy and radiation therapy. It is a highly aggressive B-cell neoplasm with not all patients cured, in spite of current therapies. This study evaluated the effects of traditional Chinese medicine Marsdenia tenacssima (MTE) and its component compound Tenacigenoside A (TGTA) and 11α-O-benzoyl-12ß-O-acetyltenacigenin B (TGTB) on human Burkitt lymphoma growth. It was observed that MTE, TGTA or TGTB inhibited cell growth and induced apoptosis of Burkitt lymphoma cells in culture. In lymphoma bearing NOD/SCID nude mice, both TGTA and TGTB inhibited tumor growth and improved animal survival. TGTA and TGTB significantly increased tumor cell apoptosis on lymphoma bearing mice, primarily through down-regulation of BCL2 and BCL-XL and up-regulation of BID.
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OBJECTIVE: To investigate the relationship of the mutational status of the ND4 gene and the clinical features of acute myelogenous leukemia (AML) patients with ND4 mutations. METHODS: Using PCR combined with directly sequencing, we identified somatic mutations of ND4 in 121 primary AML patients to couple with their clinical features. RESULTS: There were 58 male patients and 63 female patients (median age 49 years, 10-86 years). Eight of 121 patients (6.6%) with de novo AML were found harboring missense mutation of ND4 gene, including 3 patients with A131V (3/8, 37.5%), 2 patients with A404T (2/8, 25%), 1 patient with F149L (1/8, 12.5%), 1 patient with G242D (1/8, 12.5%) and 1 patient with Y409H (1/8, 12.5%), respectively. Patients with ND4 mutations were associated with good karyotype (P=0.049), regardless of gender, age, white blood cell, hemoglobin, platelet, blast cells of bone marrow or immunophenotype (P>0.05). There were no statistical significance in mutations of FLT3-ITD, NPM1, CEBPA, c-KIT and DNMT3A between patients with ND4 mutation and wild-type (wt) ND4 (P>0.05). The median overall survival of patients with ND4 mutations and wt ND4 were all not reached. The median relapse-free survival were not reached and 29(2-53) months, respectively (P>0.05). There was no significance in the ratio of CR and RR patients between wt ND4 and ND4 mutated groups (P>0.05). CONCLUSION: It was concluded that novel ND4 mutations could be found in de novo AML patients, especially in patients with good karyotype. Thus, ND4 mutations might play an important role in AML prognosis. However, whether the mitochondria dysfunction contribute to leukemogenesis needs to be further investigated.