Chen X.,Sichuan Academy of Medical science
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2016
OBJECTIVES: By combining the metabolomics and computational biology, to explore the relationship between metabolic phenotype and pathological stage in esophageal cancer patients, to find the mechanism of metabolic network disturbance and develop a new method for fast preoperative clinical staging.METHODS: A prospective cohort study (from April 2013 to January 2016) was conducted. The preoperative patients from Sichuan Provincial People's Hospital, who were diagnosed with esophageal cancer from May 2013 to April 2014 were included, and their serum samples were collected to detect (1)H-nuclear magnetic resonance (NMR) metabolomics for the purpose of drawing the metabolic fingerprinting in different stages of patients with esophageal cancer. The data were processed with these methods-principal components analysis: partial least squares regression and support vector machine, for the exploration of the enzyme-gene network regulatory mechanism in abnormal esophageal cancer metabolic network regulation and to build the quantitative prediction model of esophageal cancer staging in the end. All data were processed on high-performance computing platforms Matalab. The comparison of data had used Wilcoxon test, variance analysis, χ(2) test and Fisher exact test.RESULTS: Twenty patients with different stages of esophageal cancer were included; and their serum metabolic fingerprinting could differentiate different tumor stages. There were no difference among the five teams in the age (F=1.086, P>0.05), the body mass index (F=1.035, P>0.05), the distance from the incisors to tumor (F=1.078, P>0.05). Among the patients with different TNM stages, there was a significant difference in plasma metabolome. Compared to ⅡB, ⅢA, Ⅳstage patients, increased levels of butanone, ethanol amine, homocysteine, hydroxy acids and estriol, together with decreased levels of glycoprotein, creatine, choline, isobutyricacid, alanine, leucine, valine, were observed inⅠB, ⅡA stage patients. Four metabolic markers (ethanol amine, hydroxy-propionic acid, homocysteine and estriol) were eventually selected. gene ontology analysis showed that 54 enzymes and genes regulated the 4 key metabolic markers. The quantitative prediction model of esophageal cancer staging based on esophageal cancer NMR spectrum were established. Cross-validation results showed that the predicted effect was good (root mean square error=5.3, R(2)=0.47, P=0.036).CONCLUSIONS: The systems biology approaches based on metabolomics and enzyme-gene regulatory network analysis can be used to quantify the metabolic network disturbance of patients with advanced esophageal cancer, and to predict preoperative clinical staging of esophageal cancer patients by plasma NMR metabolomics.
Yu Y.,Mayo Medical School |
Yu Y.,Sichuan Academy of Medical science |
Villarraga H.R.,Mayo Medical School |
Saleh H.K.,Mayo Medical School |
And 2 more authors.
International Journal of Cardiovascular Imaging | Year: 2013
Strain and strain rate (SR) measured with 2-dimensional speckle tracking echocardiography (2-D STE) can quantitatively assess myocardial function. Our aim was to evaluate whether we could detect abnormalities in strain, strain rate, and dyssynchrony by applying 2-D STE in patients with severe coronary artery disease during early stages of dobutamine stress echocardiography. Thirty-four patients with angiographically documented severe 3-vessel coronary artery disease and preserved left ventricular ejection fraction were compared with 42 control patients without evidence of coronary artery disease. Circumferential and longitudinal strain, SR, and left ventricular synchrony using standard deviation (SD) of time to systolic peak strain and SR were analyzed with 2-D STE at rest and at intermediate doses of dobutamine stress echocardiography. Compared with control subjects, patients with coronary artery disease showed lower circumferential SR [-1.42 (0.34) s-1 vs -1.64 (0.34) s-1; P <.02] and significantly lower longitudinal strain [-15.41 % (3.52 %) vs -19.37 % (3.21 %); P <.001] and SR [-0.91 (0.18) s -1 vs -1.19 (0.24) s-1; P <.001] at intermediate doses; these values were also compromised at peak dose. The SD of longitudinal time to systolic peak strain at intermediate dose was significantly greater in patients with coronary artery disease than in control patients [37.89 (12.32) vs 27.21 (10.86); P <.001]. The 2-D STE-derived strain and SR detected myocardial dysfunction and asynchrony in patients with coronary artery disease during intermediate doses of dobutamine stress, with minimal changes in regional wall motion abnormalities at this stage. © 2012 Springer Science+Business Media, B.V.
Huang R.,Wenzhou Central Hospital |
Zhong T.,Sichuan Academy of Medical science |
Wu H.,Wenzhou Central Hospital
Archives of Medical Science | Year: 2015
Introduction: Acute lung injury (ALI) is an acute inflammatory disease characterized by excess production of inflammatory factors in lung tissue. Quercetin, a herbal flavonoid, exhibits anti-inflammatory and anti-oxidative properties. This study was performed to assess the effects of quercetin on lipopolysaccharide (LPS)-induced ALI. Material and methods: Sprague-Dawley rats were randomly divided into 3 groups: the control group (saline alone), the LPS group challenged with LPS (Escherichia coli 026:B6; 100 μg/kg), and the quercetin group pretreated with quercetin (50 mg/kg, by gavage) 1 h before LPS challenge. Bronchoalveolar lavage fluid (BALF) samples and lung tissues were collected 6 h after LPS administration. Histopathological and biochemical parameters were measured. Results: The LPS treatment led to increased alveolar wall thickening and cellular infiltration in the lung, which was markedly prevented by quercetin pretreatment. Moreover, quercetin significantly (p < 0.05) attenuated the increase in the BALF protein level and neutrophil count and lung wet/dry weight ratio and myeloperoxidase activity in LPS-challenged rats. The LPS exposure evoked a 4- to 5-fold rise in BALF levels of tumor necrosis factor-α and interleukin-6, which was significantly (p < 0.05) counteracted by quercetin pretreatment. Additionally, quercetin significantly (p < 0.05) suppressed the malondialdehyde level and increased the activities of superoxide dismutase, catalase, and glutathione peroxidase in the lung of LPS-treated rats. Conclusions: Quercetin pretreatment effectively ameliorates LPS-induced ALI, largely through suppression of inflammation and oxidative stress, and may thus have therapeutic potential in the prevention of this disease. Copyright © 2015 Termedia & Banach.
Ma H.,Soochow University of China |
Liu J.,Sichuan Academy of Medical science |
Ali M.M.,University of California at Irvine |
Mahmood M.A.I.,University of Texas at Arlington |
And 8 more authors.
Chemical Society Reviews | Year: 2015
Aptamers are single-stranded DNA or RNA oligomers, identified from a random sequence pool, with the ability to form unique and versatile tertiary structures that bind to cognate molecules with superior specificity. Their small size, excellent chemical stability and low immunogenicity enable them to rival antibodies in cancer imaging and therapy applications. Their facile chemical synthesis, versatility in structural design and engineering, and the ability for site-specific modifications with functional moieties make aptamers excellent recognition motifs for cancer biomarker discovery and detection. Moreover, aptamers can be selected or engineered to regulate cancer protein functions, as well as to guide anti-cancer drug design or screening. This review summarizes their applications in cancer, including cancer biomarker discovery and detection, cancer imaging, cancer therapy, and anti-cancer drug discovery. Although relevant applications are relatively new, the significant progress achieved has demonstrated that aptamers can be promising players in cancer research. This journal is © The Royal Society of Chemistry.
Xiong F.,Sichuan Academy of Medical science
PLoS ONE | Year: 2015
Hepatocellular carcinoma is one of the most common malignancies worldwide, with a high risk of portal vein tumor thrombus (PVTT). Some promising results have been achieved for venous metastases of hepatocellular carcinoma; however, the etiology of PVTT is largely unknown, and it is unclear why the incidence of PVTT is not proportional to its distance from the carcinoma. We attempted to address this issue using physical concepts and mathematical tools. Finally, we discuss the relationship between the probability of a collision event and the microenvironment of the PVTT. Our formulae suggest that the collision probability can alter the tumor microenvironment by increasing the number of tumor cells. © 2015 Fei Xiong. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Xiao H.T.,Sichuan Academy of Medical science
European review for medical and pharmacological sciences | Year: 2012
Asthma is a major epidemic affecting up to one third people in developed countries over the last decades, and making a crucial impact on morbidity rates. The classical characters of asthma in human are airway inflammation, airway hyperreactivity, and airway remodeling. Hygiene hypothesis, inflammation cells and signaling pathway in asthma were involved in Toll-like receptors (TLRs). TLRs are a kind of pattern recognition receptors, which are important in recognition of various pathogens. TLRs have been seen as a key target for asthma treatment, so a promising approach for asthma treatment was adopted to the multiwayly modulating toll-like receptors way.
Hu J.,Sichuan Academy of Medical science
Advances in Experimental Medicine and Biology | Year: 2010
Objective: To investigate protamine sulfate inhibition of expression of the vascular endothelial growth factor (VEGF) and VEGF-VEGFR binding in vitro and to find a new drug that inhibits neovascularization, which can potentially be used to treat angiogenic eye diseases such as diabetic retinopathy and age-related macular degeneration (AMD). Methods: Monkey retinal vascular endothelial cells (RF/6A) were cultured in vitro and different concentrations of protamine sulfate were added to the vascular endothelial cells after three passages. VEGF expression level was examined by ELISA and immunohistochemistry after the cells were treated with protamine sulfate. Results: VEGF expression decreased in a dose-dependent pattern in 10-80 μg/ml of protamine sulfate. We also found that protamine sulfate could inhibit VEGF to bind to its receptor, VEGFR. Conclusion: Protamine sulfate could inhibit VEGF expression and VEGF-VEGFR binding in vitro. Protamine sulfate may be used for inhibiting neovascularization in angiogenic eye diseases. © Springer Science+Business Media, LLC 2010.
Zhang L.,Peking University |
Wang F.,Peking University |
Wang L.,Sichuan Academy of Medical science |
Wang W.,Chifeng Second Hospital |
And 20 more authors.
The Lancet | Year: 2012
Background: The prevalence of chronic kidney disease is high in developing countries. However, no national survey of chronic kidney disease has been done incorporating both estimated glomerular filtration rate (eGFR) and albuminuria in a developing country with the economic diversity of China. We aimed to measure the prevalence of chronic kidney disease in China with such a survey. Methods: We did a cross-sectional survey of a nationally representative sample of Chinese adults. Chronic kidney disease was defined as eGFR less than 60 mL/min per 1·73 m2 or the presence of albuminuria. Participants completed a lifestyle and medical history questionnaire and had their blood pressure measured, and blood and urine samples taken. Serum creatinine was measured and used to estimate glomerular filtration rate. Urinary albumin and creatinine were tested to assess albuminuria. The crude and adjusted prevalence of indicators of kidney damage were calculated and factors associated with the presence of chronic kidney disease analysed by logistic regression. Findings: 50 550 people were invited to participate, of whom 47 204 agreed. The adjusted prevalence of eGFR less than 60 mL/min per 1·73 m2 was 1·7 (95 CI 1·5-1·9) and of albuminuria was 9·4 (8·9-10·0). The overall prevalence of chronic kidney disease was 10·8 (10·2-11·3); therefore the number of patients with chronic kidney disease in China is estimated to be about 119·5 million (112·9-125·0 million). In rural areas, economic development was independently associated with the presence of albuminuria. The prevalence of chronic kidney disease was high in north (16·9 [15·1-18·7]) and southwest (18·3 [16·4-20·4]) regions compared with other regions. Other factors independently associated with kidney damage were age, sex, hypertension, diabetes, history of cardiovascular disease, hyperuricaemia, area of residence, and economic status. Interpretation: Chronic kidney disease has become an important public health problem in China. Special attention should be paid to residents in economically improving rural areas and specific geographical regions in China. Funding: The Ministry of Science and Technology (China); the Science and Technology Commission of Shanghai; the National Natural Science Foundation of China; the Department of Health, Jiangsu Province; the Sichuan Science and Technology Department; the Ministry of Education (China); the International Society of Nephrology Research Committee; and the China Health and Medical Development Foundation. © 2012 Elsevier Ltd.
Wen H.-L.,Central South University |
Wen H.-L.,Sichuan Academy of Medical science |
Liang Z.-S.,Central South University |
Zhang R.,The Seventh Peoples Hospital of Chengdu |
Yang K.,Central South University
Cardiovascular Diabetology | Year: 2013
Aims: Given the importance of inflammation in the onset and progression of diabetic cardiomyopathy, we investigated the potential protective effects of triptolide, an anti-inflammatory agent, in streptozotocin-induced diabetic rat model and in H9c2 rat cardiac cells exposed to high glucose. Methods and results: Diabetic rats were treated with triptolide (100, 200, or 400 μg/kg/day respectively) for 6 weeks. At the end of this study, after cardiac function measurements were performed, rats were sacrificed and their hearts were harvested for further histologic and molecular biologic analysis. Enhanced activity and expression of nuclear factor-kappaB (NF-κB) p65 in diabetic hearts were associated with increased inflammatory response, as demonstrated by increased pro-inflammatory cytokines, cell adhesion molecules and invading inflammatory cells, as well as increased fibrosis, in line with impaired left ventricular function. Triptolide attenuated these morpho-functional alterations. Furthermore, triptolide (20 ng/ml) also attenuated high glucose-induced inflammation in H9c2 rat cardiac cells. Conclusion: Our data demonstrate that anti-inflammatory effects of triptolide involving the NF-κB signaling pathway can improve left ventricular function under diabetic conditions, suggesting triptolide treatment might be beneficial in diabetic cardiomyopathy. © 2013 Wen et al.; licensee BioMed Central Ltd.
Fan Y.,Sichuan Academy of Medical science
Advances in Experimental Medicine and Biology | Year: 2010
Background: A project originally developed for NASA plant growth experiments in space demonstrating the Light-Emitting Diode (LED) could promote the wound healing. Further study showed that the LED's could protect cells by stimulating the basic energy processes in the mitochondria of each cell. Objective: The purpose of this study was to assess the effects of 670 nm LED to protect the photoreceptor from the light-induced damage in a rodent model. Methods: SD rats were randomly assigned to one of eight groups: untreated control group, the LED-treated control group, three light-induced damage groups, and three LED-protected groups. The rats were exposed to constant light for 3 h of different illuminations of 900, 1,800 and 2,700 lux, respectively. The LED treatment (50mW) were done for 30 min, 3 h before the light damage and 0, 24 and 48 h after the light damage. Using the electroretinogram as a sensitive indicator of retinal function, and the histopathologic change was showed as a proof of the protective effect of LED treatment. Results: The 900 lux illumination for 3 h did not cause damage to the retina of rats, however, the 1,800 lux illumination for 3 h caused significant damage to ONL of an approximate half retina, which caused the swing of ERG b wave to be 431 μV. With the LED protection: the damage of ONL was near 1/6 of retina, which was significantly reduced than the ones without LED protection (P < 0.01); and the swing of ERG b wave was recorded to be 1,011 μV, which was increased significantly than the ones without LED protection (P < 0.01). The illumination of 2,700 lux for 3 h caused severe damage to the rats' retinas and the LED could not protect them significantly in both of morphology and function (P > 0.05, P > 0.05). Conclusions: 670 nm LED treatment has an evident protective effect on retinal cells against light-induced damage, which may be an innovative and non-invasive therapeutic approach to prevent or to delay age-related macular degeneration. © Springer Science+Business Media, LLC 2010.