Publications by authors named "Baoying Chen"

22 Publications

  • Page 1 of 1

Integrative Proteomic and Metabolomic Analysis Reveals Metabolic Phenotype in Mice With Cardiac-Specific Deletion of Natriuretic Peptide Receptor A.

Mol Cell Proteomics 2021 Mar 31;20:100072. Epub 2021 Mar 31.

Clinical Experimental Center, Xi'an International Medical Center Hospital, Xi'an, P.R. China. Electronic address:

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are important biological markers and cardiac function regulators. Natriuretic peptide receptor A (NPRA) binds to an ANP or BNP ligand and induces transmembrane signal transduction by elevating the intracellular cyclic guanosine monophosphate (cGMP) levels. However, the metabolic phenotype and related mechanisms induced by NPRA deletion remain ambiguous. Here, we constructed myocardial-specific NPRA deletion mice and detected the heart functional and morphological characteristics by histological analysis and explored the altered metabolic pattern and the expression patterns of proteins by liquid chromatography-mass spectrometry (LC-MS)-based omics technology. NPRA deficiency unexpectedly did not result in significant cardiac remodeling or dysfunction. However, compared with the matched littermates, NPRA-deficient mice had significant metabolic differences. Metabolomic analysis showed that the metabolite levels varied in cardiac tissues and plasma. In total, 33 metabolites were identified in cardiac tissues and 54 were identified in plasma. Compared with control mice, NPRA-deficient mice had 20 upregulated and six downregulated metabolites in cardiac tissues and 25 upregulated and 23 downregulated metabolites in plasma. Together, NPRA deficiency resulted in increased nucleotide biosynthesis and histidine metabolism only in heart tissues and decreased creatine metabolism only in plasma. Further proteomic analysis identified 136 differentially abundant proteins in cardiac tissues, including 54 proteins with higher abundance and 82 proteins with lower abundance. Among them, cytochrome c oxidase subunit 7c and 7b (Cox7c, Cox7b), ATP synthase, H+ transporting, mitochondrial Fo complex subunit F2 (ATP5J2), ubiquinol-cytochrome c reductase, complex III subunit X (Uqcr10), and myosin heavy chain 7 (Myh7) were mainly involved in related metabolic pathways. These results revealed the essential role of NPRA in metabolic profiles and may elucidate new underlying pathophysiological mechanisms of NPRA in cardiovascular diseases.
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http://dx.doi.org/10.1016/j.mcpro.2021.100072DOI Listing
March 2021

Endoscopic Endonasal Transsphenoidal Approach for Third Ventriculostomy in the Management of Obstructive Hydrocephalus.

J Craniofac Surg 2021 Mar 5. Epub 2021 Mar 5.

Department of Neurosurgery, Xi'an International Medical Center Department of Neurosurgery, Xi'an Fengcheng Hospital Department of Radiology, Xi'an International Medical Center Department of Anesthesiology and Operation Center, Xi'an International Medical Center, Xi'an, Shaanxi Province, China.

Abstract: Endoscopic third ventriculostomy (ETV) is a safe and effective method for the management of obstructive hydrocephalus. Traditional approach is a transfrontal trajectory through the foramen of Monro to access and open the third ventricle floor. Though endoscopic endonasal transsphenoidal approach (EETA) for pituitary and skull base tumors has become increasingly popular, no published literature has explored its utility in performing an ETV. Here, the authors reported a successful ETV for obstructive hydrocephalus through the EETA. A 57-year-old male presenting with progressive headache and gait disturbance for 3 months was diagnosed with obstructive hydrocephalus. Brain MRI revealed an obstruction of cerebrospinal fluid (CSF) flow at the cerebral aqueduct and supratentorial hydrocephalus, accompanied with dilatation and downward herniation of the third ventricle floor. Considering the displacement of the third ventricle floor and the indication for surgery, an ETV was successfully performed through the EETA. No postoperative complication was observed. Both radiological and clinical evaluation postoperatively confirmed ETV success with decreased ventricular size, increased CSF flow across the floor of the third ventricle, and improved clinical signs. EETA is a feasible approach for ETV in selected cases of obstructive hydrocephalus. This approach provides a short trajectory to directly visualize and open the Liliequist's membrane and the displaced floor of the third ventricle, while minimizes damage to normal brain tissue. Skull base repair with nasoseptal flap ensures the success rate by preventing postoperative CSF leak and infection.
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http://dx.doi.org/10.1097/SCS.0000000000007613DOI Listing
March 2021

Metabonomics Analysis of Myocardial Metabolic Dysfunction in Patients with Cardiac Natriuretic Peptide Resistance.

Cardiol Res Pract 2020 9;2020:1416945. Epub 2020 Dec 9.

Clinical Experimental Center, Xi'an International Medical Center Hospital, Xi'an 710100, China.

Brain natriuretic peptide (BNP) is an important biological marker and regulator of cardiac function. BNP resistance is characterized by high concentrations of less functionally effective BNP and common in heart failure (HF) patients. However, the roles and consequences of BNP resistance remain poorly understood. Investigate the effects of cardiac BNP resistance and identify potential metabolic biomarkers for screening and diagnosis. Thirty patients and thirty healthy subjects were enrolled in this study. Cardiac functions were evaluated by echocardiography. The plasma levels of cyclic guanosine monophosphate (cGMP) and BNP were measured by enzyme-linked immunosorbent assay (ELISA) and the cGMP/BNP ratio is calculated to determine cardiac natriuretic peptide resistance. Liquid chromatograph tandem mass spectrometry (LC-MS) based untargeted metabolomics analysis was applied to screen metabolic changes. The cGMP/BNP ratio was markedly lower in HF patients than controls. The cGMP/BNP ratio and ejection fraction (EF) were strongly correlated (  = 0.676, < 0.05). Importantly, metabolic profiles were substantially different between HF patients and healthy controls. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the differentially expressed metabolites are involved in signaling pathways that regulate cardiac functions. In HF patients, BNP resistance develops in association with a reduction in heart function and metabolic remodeling. It suggests possible functional roles of BNP resistance in the regulation of cardiac metabolism.
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http://dx.doi.org/10.1155/2020/1416945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744244PMC
December 2020

Cardiac‑specific deletion of natriuretic peptide receptor A induces differential myocardial expression of circular RNA and mRNA molecules involved in metabolism in mice.

Mol Med Rep 2021 01 17;23(1). Epub 2020 Nov 17.

Clinical Experimental Centre, Xi'an International Medical Centre Hospital, Xi'an, Shaanxi 710100, P.R. China.

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are important biological markers and regulators of cardiac function. The natriuretic peptide receptor A (NPRA), also known as NPR1 or guanylyl cyclase A, binds ANP and BNP to initiate transmembrane signal transduction by elevating the intracellular levels of cyclic guanosine monophosphate. However, the effects and mechanisms downstream of NPRA are largely unknown. The aim of the present study was to evaluate the changes in the global pattern of mRNA and circular RNA (circRNA) expression in NPRA‑/‑ and NPRA+/+ myocardium. Differentially expressed mRNA molecules were characterised using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis and were found to be primarily related to metabolic processes. Moreover, circRNA expression was also examined, and a possible competing endogenous RNA network consisting of circRNA, microRNA (miRNA), and mRNA molecules was constructed. The results of this study indicated that NPRA may play a role in cardiac metabolism, which could be mediated by circRNA through endogenous competition mechanisms. These findings may provide insight into future characterisation of various ceRNA network pathways.
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http://dx.doi.org/10.3892/mmr.2020.11688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706000PMC
January 2021

Reconstruction of the chest wall in locally advanced breast cancer with multi-disciplinary cooperation: a case report of mesh repair plus TRAM combined with DIEP chest wall reconstruction.

Gland Surg 2020 Aug;9(4):1048-1055

Department of Breast Surgery, Oncology, Chest Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.

Locally advanced breast cancer, which is defined as a malignant breast tumor that invades or adheres to the surrounding tissue, is characterized by the invasion of the chest wall and the skin surface by the tumor. Multiple lymph nodes are invaded and fuse into a mass, causing extensive axillary lymph node metastasis. However, locally advanced breast cancer does not exhibit distant metastasis. At present, in most hospitals in China and the rest of the world, this type of breast cancer is primarily managed through systematic and local treatments. However, a consensus concerning the optimal surgical method for chest wall reconstruction, which for many surgeons is a difficult and confusing procedure, has not been reached. In the past, many breast centers had used skin flap combined with hard mesh titanium alloy plate to repair the large chest wall defects. Although titanium alloy plate can maintain the stability of the chest wall, it may have a negative effect on the follow-up radiotherapy of breast cancer patients, which is a controversial method. In addition, titanium alloy mesh also has the risk of deformation and fracture. These factors will cause some hidden dangers to patient safety. According to the research, the soft mesh not only has the characteristics of satisfactory compatibility and robustness for maintaining the stability of chest wall, but also does not affect the postoperative radiotherapy of patients. Combined with the advantages of soft mesh, Our department treated a case of locally advanced breast cancer with chest wall invasion. Through cooperation between the breast surgery and thoracic surgery departments, a mesh repair plus transverse rectus abdominis myocutaneous (TRAM) combined with deep inferior epigastric perforator (DIEP) procedure was performed to remove the breast tumor and repair the large area of skin defect after surgery, and a relatively satisfactory therapeutic effect was achieved. In this case, we took two novel approaches: first, a 4-layer high-density polyethylene mesh was used to repair the defect; secondly, the inferior epigastric artery perforation was anastomosed with the thoracoacromial artery (end-to-end anastomosis) and the inferior epigastric vein perforation was anastomosed with the axillary vein (end-to-side anastomosis).
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http://dx.doi.org/10.21037/gs-20-436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475378PMC
August 2020

A knowledge-driven feature learning and integration method for breast cancer diagnosis on multi-sequence MRI.

Magn Reson Imaging 2020 06 12;69:40-48. Epub 2020 Mar 12.

Imaging Diagnosis and Treatment Center, Xi'an International Medical Center Hospital, Xi'an, 710100, P.R. China. Electronic address:

Background: The classification of benign versus malignant breast lesions on multi-sequence Magnetic Resonance Imaging (MRI) is a challenging task since breast lesions are heterogeneous and complex. Recently, deep learning methods have been used for breast lesion diagnosis with raw image input. However, without the guidance of domain knowledge, these data-driven methods cannot ensure that the features extracted from images are comprehensive for breast cancer diagnosis. Specifically, these features are difficult to relate to clinically relevant phenomena.

Purpose: Inspired by the cognition process of radiologists, we propose a Knowledge-driven Feature Learning and Integration (KFLI) framework, to discriminate between benign and malignant breast lesions using Multi-sequences MRI.

Methods: Starting from sequence division based on characteristics, we use domain knowledge to guide the feature learning process so that the feature vectors of sub-sequence are constrained to lie in characteristic-related semantic space. Then, different deep networks are designed to extract various sub-sequence features. Furthermore, a weighting module is employed for the integration of the features extracted from different sub-sequence images adaptively.

Results: The KFLI is a domain knowledge and deep network ensemble, which can extract sufficient and effective features from each sub-sequence for a comprehensive diagnosis of breast cancer. Experiments on 100 MRI studies have demonstrated that the KFLI achieves sensitivity, specificity, and accuracy of 84.6%, 85.7% and 85.0%, respectively, which outperforms other state-of-the-art algorithms.
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http://dx.doi.org/10.1016/j.mri.2020.03.001DOI Listing
June 2020

Swimming exercise inhibits myocardial ER stress in the hearts of aged mice by enhancing cGMP‑PKG signaling.

Mol Med Rep 2020 Feb 5;21(2):549-556. Epub 2019 Dec 5.

Department of Physiology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

The purpose of the present study was to explore aging‑associated cardiac dysfunction and the possible mechanism by which swimming exercise modulates cardiac dysfunction in aged mice. Aged mice were divided into two groups: i) Aged mice; and ii) aged mice subjected to swimming exercises. Another cohort of 4‑month‑old male mice served as the control group. Cardiac structure and function in mice were analyzed using hematoxylin and eosin staining, and echocardiography. The levels of oxidative stress were determined by measuring the levels of superoxide dismutase, malondialdehyde and reactive oxygen species (ROS). Levels of the endoplasmic reticulum (ER) stress‑related protein PKR‑like ER kinase, glucose‑regulated protein 78 and C/EBP homologous protein were determined to evaluate the level of ER stress. The aged group exhibited an abnormal cardiac structure and decreased cardiac function, both of which were ameliorated by swimming exercise. The hearts of the aged mice exhibited pronounced oxidative and ER stress, which were ameliorated by exercise, and was accompanied by the reactivation of myocardial cGMP and suppression of cGMP‑specific phosphodiesterase type 5 (PDE5). The inhibition of PDE5 attenuated age‑induced cardiac dysfunction, blocked ROS production and suppressed ER stress. An ER stress inducer abolished the beneficial effects of the swimming exercise on cardiac function and increased ROS production. The present study suggested that exercise restored cardiac function in mice with age‑induced cardiac dysfunction by inhibiting oxidative stress and ER stress, and increasing cGMP‑protein kinase G signaling.
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http://dx.doi.org/10.3892/mmr.2019.10864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947875PMC
February 2020

Occurrence of antibiotic resistance genes in extracellular and intracellular DNA from sediments collected from two types of aquaculture farms.

Chemosphere 2019 Nov 15;234:520-527. Epub 2019 Jun 15.

Southern Marine Science and Engineering Guangdong Laboratory, School of Marine Sciences, Sun Yat-Sen University, Zhuhai, 519082, China; Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-Sen University, Guangzhou, 510275, China. Electronic address:

The occurrence and quantities of ARGs in extracellular and intracellular DNA (eARGs and iARGs) from sediments collected in two different types of aquaculture farms were investigated. A total of 20 ARG subtypes associated with 7 categories of commonly used antibiotics (e.g., aminoglycosides, beta-lactams, sulfonamides, tetracyclines) were identified, and some of these subtypes were not related to the antibiotics used. ARGs are mainly present in the iDNA form with the ratio of the total iARGs to eARGs being in the range of 7.9-45.5. The ratio of eARG to iARGs varies greatly with ARG subtypes, probably due to their differences in persistence as a part of eDNA. Significant correlation between int1 and ARGs was observed for both eDNA and iDNA in sediments from the aquaculture farms. Moreover, ARG pollution was more serious in bullfrog ponds than polyculture ponds due to the more frequent use of antibiotics in bullfrog rearing operations.
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http://dx.doi.org/10.1016/j.chemosphere.2019.06.085DOI Listing
November 2019

B-type natriuretic peptide attenuates endoplasmic reticulum stress in H9c2 cardiomyocytes underwent hypoxia/reoxygenation injury under high glucose/high fat conditions.

Peptides 2019 01 22;111:103-111. Epub 2018 Apr 22.

Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Xi'an Medical University, Xi'an, China; Department of Cardiology, Second Affiliated Hospital, Xi'an Medical University, Xi'an, China. Electronic address:

Exogenously administered B-type natriuretic peptide (BNP) has been shown to provide cardioprotection against various heart diseases. However, the underlying mechanisms remain elusive. This study explores whether BNP exerts its cardioprotection against hypoxia/reoxygenation (H/R) injury under high glucose/high fat (HG/HF) conditions in cardiac H9c2 cells and uncovers the underlying mechanisms. Our data revealed that BNP significantly increased the cell viability and decreased the release of lactate dehydrogenase (LDH) and creatine kinase (CK), with a maximal effect at the BNP concentration of 10 mol/L. In addition, by analyzing the activation of cleaved caspase-3 and by Annexin V-FITC/PI staining, we showed that BNP attenuated H/R-induced cell apoptosis in HG/HF conditions. Western blot analysis showed enhanced phosphorylation of protein kinase RNA (PKR)-like endoplastmic reticulum (ER) kinase (PERK) and eukaryotic initiation factor 2α (eIF2α)(one of the three main signaling pathways in endoplastmic reticulum (ER) stress), and increased expression of GRP78 and CHOP proteins (ER stress-related proteins) in H9c2 cells which underwent H/R in HG/HF conditions. Treatment with BNP or 8-Br-cGMP (an analog of cGMP) reversed this activation. However, this effect was significantly weakened by KT-5823, a selective cGMP-dependent protein kinase G (PKG) inhibitor. In addition, similar to BNP, treatment with a specific inhibitor of ER stress tauroursodeoxycholic acid (TUDCA) protected the cells against H/R injury exposed to HG/HF conditions. In conclusion, these findings demonstrated that BNP effectively protected cells against H/R injury under HG/HF conditions by inhibiting the ER stress via activation of the cGMP-PKG signaling pathway.
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http://dx.doi.org/10.1016/j.peptides.2018.04.016DOI Listing
January 2019

MiR-204/ZEB2 axis functions as key mediator for MALAT1-induced epithelial-mesenchymal transition in breast cancer.

Tumour Biol 2017 Jul;39(7):1010428317690998

Oncology Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.

Long non-coding RNAs recently were identified as key mediators of cancer metastasis. This study provided evidence that long non-coding RNA MALAT1 was up-regulated in breast cancer tissues and cell lines. MALAT1 promoted cancer cell invasion through inducing epithelial-mesenchymal transition. Interestingly, we revealed there was a reciprocal repression between MALAT1 and miR-204. ZEB2 was identified as a downstream target of miR-204 and MALAT1 exerted its function mainly through the miR-204/ZEB2 axis. Our findings suggested that MALAT1 may serve as a new diagnostic biomarker and therapy target for breast cancer.
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http://dx.doi.org/10.1177/1010428317690998DOI Listing
July 2017

Down-regulation of miR-133a as a poor prognosticator in non-small cell lung cancer.

Gene 2016 Oct 6;591(2):333-7. Epub 2016 Jun 6.

Oncology Center, Affiliated Hospital of Guangdong Medical University, No. 57 Peoples Avenue South, Zhanjiang, Guangdong 524001, People's Republic of China. Electronic address:

miR-133a has been demonstrated to play an important role in tumor progression. The aim of present study was to analyze the correlation between miR-133a expression level and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). The expression of miR-133a in 104 pairs of human lung cancer tissues and adjacent normal lung tissues were analyzed by qRT-PCR. Here we show that miR-133a was down-regulated in NSCLC. The levels of miR-133a were negatively correlated with the status of N classification (N0-N1 vs. N2-N3, P=0.000), clinical stage (I-II vs. III-IV, P=0.010) and MMP-14 expression (High vs. Low, P=0.012). The patients with low miR-133a expression had shorter survival time than those with high miR-133a expression. Multivariate analysis indicated that the level of miR-133a expression was an independent prognostic indicator (P=0.012) for the survival of patients with NSCLC. In conclusion, decreased expression of miR-133a might be a potential unfavorable prognostic factor for patients with NSCLC, and further studies would be needed to prove our findings.
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http://dx.doi.org/10.1016/j.gene.2016.06.001DOI Listing
October 2016

A retrospective survey of quality of reporting on randomized controlled trials of metformin for polycystic ovary syndrome.

Trials 2014 Apr 17;15:128. Epub 2014 Apr 17.

Department of Traditional Chinese Medicine, The First People's Hospital of Shunde, Foshan, PR China.

Background: From previous reviews, there still have been controversies over the effect of metformin (MET) on reproductive function in PCOS patients. The reasons for the inconsistent findings especially lie in the transparency and accuracy of randomized controlled trials (RCTs) reports. However, we could find no data about the quality of RCTs reporting in MET for PCOS. Thus, a retrospective survey related to the quality of reporting in MET for PCOS was conducted.

Methods: A retrospective survey was conducted by two investigators. Two investigators assessed the quality of overall reporting and key methodological factors reporting using items from the CONSORT 2010 statement.

Results: A total of 39 RCTs were included in full text. The median overall quality score was 9, with a minimum of 2 and a maximum of 13. Good or general reporting existed in 11 items with positive rate of more than or equal to 50%. The median score of key methodological items was 4 with a minimum of 0 and a maximum of 5. Randomization, allocation concealment, blinding, baseline characteristics and intention-to-treat (ITT) analysis were reported in 26 (67%), 19 (49%), 20 (51%), 38 (97%) and 17 (44%) of the 39 RCTs, respectively. After adjustment, the mean overall score increased by about 1.71 for manuscripts with funding source (95% CI, 0.18 to 3.24), while it increased by about 3.51 for manuscripts published in one year increment (95% CI, 1.82 to 5.19). There was a relatively close, significant correlation (r = 0.589, P < 0.001) between the score of overall reporting quality and year of publication.

Conclusion: Although the overall reporting quality of RCTs in MET for PCOS has improved over time, reporting of key methodological items remains poor. Reporting of RCTs on MET for PCOS should keep up with the standards of the CONSORT statement.
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http://dx.doi.org/10.1186/1745-6215-15-128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021668PMC
April 2014

The role of vascular epithelial growth factor receptor-tyrosine kinase inhibitors in the treatment of advanced breast cancer: a meta-analysis of 12 randomized controlled trials.

Curr Med Res Opin 2013 Dec 23;29(12):1691-9. Epub 2013 Sep 23.

Department of Breast Surgery, Affiliated Hospital of Guangdong Medical College , Zhanjiang, Guangdong , China.

Aim: To perform a systematic review and meta-analysis of randomized controlled trials to determine the efficacy and toxicity of approved vascular epithelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) in advanced breast cancer.

Methods: A comprehensive literature search for studies published up to August 2013 was performed. The endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3 or 4 adverse event (AEs). The pooled hazard ratio (HR) or relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials.

Results: Twelve randomized controlled trials involved 3256 patients were ultimately identified. The intention to treatment (ITT) analysis demonstrated that VEGFR-TKI therapy significantly improved ORR (RR 1.14, 95% CI: 1.03-1.28, p = 0.016), but it did not translate into benefits in PFS (HR 0.99, 95% CI: 0.81-1.22, p = 0.93) and OS (HR 1.11, 95% CI 0.99-1.24, p = 0.084) when compared to non-VEGFR-TKI therapy. Additionally, a higher incidence of grade 3 or 4 anemia, neutropenia, thrombocytopenia, diarrhea, hand-foot syndrome and fatigue was observed in VEGFR-TKI-based therapy.

Conclusions: The VEGFR-TKI-based therapy offered a significant improvement in ORR in patients with advanced breast cancer but did not benefit PFS and OS. With present available data from randomized clinical trials, we were still unable to clearly set the role of VEGFR-TKIs in the treatment of metastatic breast cancer (MBC).
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http://dx.doi.org/10.1185/03007995.2013.836080DOI Listing
December 2013

Role of glycogen synthase kinase 3β in protective effect of propofol against hepatic ischemia-reperfusion injury.

J Surg Res 2013 Nov 24;185(1):388-98. Epub 2013 May 24.

Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.

Background: It was previously reported that propofol, an intravenously administered hypnotic and anesthetic agent, protects organs from ischemia-reperfusion (I/R) injury. However, the underlying mechanisms are largely unknown. Glycogen synthase kinase 3β (GSK-3β) is known to play an important role in the oxidative stress-induced apoptosis. In this study, we investigated the role of GSK-3β and mitochondrial permeability transition pore (MPTP) in the protective effects of propofol against hepatic I/R injury.

Materials And Methods: The left and median hepatic artery and the portal vein branches were blocked by no-damage artery clips to create the model of partial ischemia (70%), and liver lobes were subjected to warm ischemia for 30, 60, 90 min, respectively. Reperfusion of 120 min was then initiated by the removal of clamp. The MPTP opening was assessed by measuring mitochondrial large amplitude swelling and mitochondrial membrane potential.

Results: Pretreatment with propofol in conditions of hepatic I/R inhibits the apoptosis of hepatocytes as evidenced by decreased terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Importantly, propofol suppressed the mitochondrial GSK-3β by promoting or preserving its phosphorylation at Ser9, thus restraining the opening of MPTP and preventing the mitochondrial swell and mitochondrial membrane potential collapse.

Conclusions: Propofol protects liver from I/R injury by sustaining the mitochondrial function, which is possibly involved with the modulation of MPTP and GSK-3β.
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http://dx.doi.org/10.1016/j.jss.2013.05.004DOI Listing
November 2013

Catalpol decreases peroxynitrite formation and consequently exerts cardioprotective effects against ischemia/reperfusion insult.

Pharm Biol 2013 Apr 22;51(4):463-73. Epub 2013 Jan 22.

Heart Center, First Hospital, Tsinghua University, Beijing, China.

Context: Peroxynitrite (ONOO(-)) formation triggers oxidative/nitrative stress and contributes to exacerbated myocardial ischemia/reperfusion (MI/R) injury. Catalpol, an iridoid glycoside, abundantly found in the roots of Rehmannia glutinosa L. that is included in the family Phrymaceae in the order Lamiales, endemic to China, was found to have neuroprotective effects. However, the effect of catalpol on MI/R injury has not been identified.

Objective: This study investigated whether catalpol attenuates oxidative/nitrative stress in acute MI/R.

Materials And Methods: Adult male rats were subjected to 30 min of myocardial ischemia and 3 h of reperfusion and were treated with saline, catalpol (5 mg/kg, i.p., 5 min before reperfusion) or catalpol plus wortmannin (15 µg/kg intraperitoneally injected 15 min before reperfusion).

Results: Pretreatment with catalpol significantly improved cardiac functions, reduced myocardial infarction, apoptosis and necrosis of cardiomyocytes after MI/R (all p < 0.05). Meanwhile, ONOO(-) formation was markedly reduced after catalpol treatment (3.01 ± 0.22 vs. 4.66 ± 0.53 pmol/mg protein in vehicle, p < 0.05). In addition, catalpol increased Akt and endothelial nitric oxide synthase phosphorylation, nitric oxide (NO) production, anti-oxidant capacity and reduced MI/R-induced inducible nitric oxide synthase expression and superoxide anion (·O(2)(-)) production in I/R hearts. PI3K inhibitor wortmannin not only blocked catalpol-induced Akt activation, but also attenuated all the beneficial effects of catalpol. Suppression of ONOO(-) formation by either catalpol or an ONOO(-) scavenger uric acid (5 mg/kg) reduced myocardial infarct size in MI/R rats.

Discussion And Conclusion: In conclusion, catalpol affords cardioprotection against MI/R insult by attenuating ONOO(-) formation, which is attributable to increased physiological NO and decreased ·O(2)(-) production.
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http://dx.doi.org/10.3109/13880209.2012.740052DOI Listing
April 2013

Effective inhibition of irradiation on human gliomas growth in vitro and in vivo after epidermal growth factor receptor silencing with RNA interference.

Neuroreport 2011 Oct;22(15):773-7

Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Xinsi Road, Xi'an, Shaan'xi, P.R. China.

In this study, we found that irradiation in the presence of small interfering RNA-epidermal growth factor receptor (EGFR) arrested U373 glioma cells in G₀ and G₁ phases, delayed cell cycle progression, and effectively inhibited cell proliferation compared with cells that received only radiotherapy. In addition, combined therapy enhanced the percent of apoptotic U373 cells in vitro and also reduced the tumor size and increased the survival rate in tumor xenograft studies. This study demonstrates the antitumor activity of ionizing radiation therapy in combination with small interfering RNA-EGFR in gliomas both in vitro and in vivo and provides a scientific rationale for targeting EGFR to enhance the sensitivity to radiotherapy in patients with glioblastoma multiforme.
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http://dx.doi.org/10.1097/WNR.0b013e32834af64fDOI Listing
October 2011

Analysis of patient dose in full field digital mammography.

Eur J Radiol 2012 May 11;81(5):868-72. Epub 2011 Mar 11.

Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Xinsi Road 1, 710038 Xi'an, Shaanxi, China.

Now, full field digital mammography (FFDM) is widely used in diagnosis of breast cancer. With the development of FFDM, the radiation dose delivered to the patients involved in an imaging protocol is of utmost concern. Here, we analyzed the average glandular dose (AGD) and entrance surface exposure (ESE) of 1397 patients (6008 images) who underwent mammographic examinations by FFDM in three modes with automatic optimization of parameters (AOP), namely STD for standard mode, CNT for contrast mode and DOSE for dose mode. In addition, exposure factors including kVp, tube loading (mAs), and target/filter combination were evaluated. As a result, the patient dose was sorted as CNT>STD>DOSE. The dose difference among the three AOP modes was mainly attributed to the selection of mAs. The AGD and breast compressed thickness were well correlated in STD and DOSE modes. However, the correlation between CNT-delivered AGD and breast compressed thickness was dependent on the range of the breast thickness and patient age. The findings on dose and exposure characteristics of the three AOP modes get useful message of patient dose in the acquisition of FFDM.
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http://dx.doi.org/10.1016/j.ejrad.2011.02.027DOI Listing
May 2012

Identification of signaling pathways involved in aberrant production of adipokines in adipocytes undergoing oxidative stress.

Arch Med Res 2009 May 21;40(4):241-8. Epub 2009 May 21.

Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Shaanxi, China.

Background And Aims: In obesity, oxidative stress is responsible for the aberrant production of adipokines such as adiponectin, plasminogen activator inhibitor (PAI)-1 and interleukin-6 (IL-6), which is causally associated with obesity-related inflammation, insulin resistance and cardiovascular disease. However, the signaling transduction pathways participating in adipokine dysregulation induced by oxidative stress are largely unknown. Thus, the aim of the present study was to identify possible involved signaling pathways.

Methods: 3T3-L1 cells were differentiated into adipocytes and underwent oxidative stress by exposure to extraneous H(2)O(2). Quantitative PCR and immunoassays were performed to determine mRNA and protein levels of adipokines (adiponectin, PAI-1 and IL-6), respectively. Possible signaling pathways involved were high-throughout identified by Bioplex phosphoprotein assays and subsequently confirmed by inhibition of the targeted protein kinases such as Akt, ERK1/2, JAK/STAT, JNK, and p70 S6K, respectively.

Results: H(2)O(2) markedly suppressed adiponectin mRNA expression as well as protein secretion; however, it enhanced PAI-1 and IL-6 production in mature adipocytes. Akt,JAK/STAT and ERK1/2 participated in the H(2)O(2)-induced increase of PAI-1 and IL-6 expression, whereas adiponectin expression was reduced by H(2)O(2) via Akt and JAK/STAT.

Conclusions: Akt and JAK/STAT are congenerous pathways through which oxidative stress downregulates adiponectin and upregulates PAI-1 and IL-6 expression. ERK1/2 participates not in H(2)O(2)-induced decrease of adiponectin expression, but in the increase of PAI-1 and IL-6.
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http://dx.doi.org/10.1016/j.arcmed.2009.03.007DOI Listing
May 2009

Comparison of tissue equalization, and premium view post-processing methods in full field digital mammography.

Eur J Radiol 2010 Oct 31;76(1):73-80. Epub 2009 May 31.

Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.

Objective: To retrospectively evaluate the diagnostic abilities of 2 post-processing methods provided by GE Senographe DS system, tissue equalization (TE) and premium view (PV) in full field digital mammography (FFDM).

Materials And Methods: In accordance with the ethical standards of the World Medical Association, this study was approved by regional ethics committee and signed informed patient consents were obtained. We retrospectively reviewed digital mammograms from 101 women (mean age, 47 years; range, 23-81 years) in the modes of TE and PV, respectively. Three radiologists, fully blinded to the post-processing methods, all patient clinical information and histologic results, read images by using objective image interpretation criteria for diagnostic information end points such as lesion border delineation, definition of disease extent, visualization of internal and surrounding morphologic features of the lesions. Also, overall diagnostic impression in terms of lesion conspicuity, detectability and diagnostic confidence was assessed. Between-group comparisons were performed with Wilcoxon signed rank test.

Results: Readers 1, 2, and 3 demonstrated significant overall better impression of PV in 29, 27, and 24 patients, compared with that for TE in 12, 13, and 11 patients, respectively (p<0.05). Significant (p<0.05) better impression of PV was also demonstrated for diagnostic information end points. Importantly, PV proved to be more sensitive than TE while detecting malignant lesions in dense breast rather than benign lesions and malignancy in non-dense breast (p<0.01).

Conclusion: PV compared with TE provides marked better diagnostic information in FFDM, particularly for patients with malignancy in dense breast.
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http://dx.doi.org/10.1016/j.ejrad.2009.05.010DOI Listing
October 2010

Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes.

Biochem Biophys Res Commun 2006 Mar 13;341(2):549-56. Epub 2006 Jan 13.

Department of Medicine, University of Hong Kong, Hong Kong, China.

Low plasma levels of adiponectin (hypoadiponectinemia) and elevated circulating concentrations of plasminogen activator inhibitor (PAI)-1 are causally associated with obesity-related insulin resistance and cardiovascular disease. However, the mechanism that mediates the aberrant production of these two adipokines in obesity remains poorly understood. In this study, we investigated the effects of hypoxia and reactive oxygen species (ROS) on production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Quantitative PCR and immunoassays showed that ambient hypoxia markedly suppressed adiponectin mRNA expression and its protein secretion, and increased PAI-1 production in mature adipocytes. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1alpha (HIF-1alpha), mimicked the hypoxia-mediated modulations of these two adipokines. Hypoxia caused a modest elevation of ROS in adipocytes. However, ablation of intracellular ROS by antioxidants failed to alleviate hypoxia-induced aberrant production of adiponectin and PAI-1. On the other hand, the antioxidants could reverse hydrogen peroxide (H2O2)-induced dysregulation of adiponectin and PAI-1 production. H2O2 treatment decreased the expression levels of peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer binding protein (C/EBPalpha), but had no effect on HIF-1alpha, whereas hypoxia stabilized HIF-1alpha and decreased expression of C/EBPalpha, but not PPARgamma. Taken together, these data suggest that hypoxia and ROS decrease adiponectin production and augment PAI-1 expression in adipocytes via distinct signaling pathways. These effects may contribute to hypoadiponectinemia and elevated PAI-1 levels in obesity, type 2 diabetes, and cardiovascular diseases.
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http://dx.doi.org/10.1016/j.bbrc.2006.01.004DOI Listing
March 2006

Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice.

Proc Natl Acad Sci U S A 2005 Apr 18;102(17):6086-91. Epub 2005 Apr 18.

Department of Medicine, Research Center of Heart, Brain, Hormone, and Healthy Aging, and Genome Research Center, University of Hong Kong, Hong Kong, China.

Angiopoietin-like protein 4 (ANGPTL4) is a circulating protein predominantly expressed in adipose tissue and liver. Several recent studies demonstrated that ANGPTL4 is the target gene of peroxisome proliferation activators, the agonists of which are widely used as the antidiabetic and lipid-lowering drugs. Here we provide evidence that ANGPTL4 is a blood-borne hormone directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity. Adenovirus-mediated expression of ANGPTL4 potently decreased blood glucose and improved glucose tolerance, whereas it induced hyperlipidemia, fatty liver, and hepatomegaly in C57 mice. In db/db diabetic mice, ANGPTL4 treatment reduced hyperglycemia to a normal level, and markedly alleviated glucose intolerance and hyperinsulinemia. Ex vivo studies on primary rat hepatocytes revealed that ANGPTL4 significantly decreased hepatic glucose production and enhanced insulin-mediated inhibition of gluconeogenesis. Serum levels of ANGPTL4 in human subjects inversely correlated with plasma glucose concentrations and HOMA IR, the homeostasis model assessment of insulin resistance. In patients with type 2 diabetes, serum levels of ANGPTL4 were significantly lower than those in healthy subjects, suggesting that the decreased ANGPTL4 could be a causative factor of this disease. These results collectively indicate that ANGPTL4 exerts distinct effects on glucose and lipid metabolism, and that its beneficial effect on glucose homeostasis might be useful for the treatment of diabetes.
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http://dx.doi.org/10.1073/pnas.0408452102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1087912PMC
April 2005

Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes.

J Biol Chem 2005 May 9;280(18):18073-80. Epub 2005 Mar 9.

Department of Medicine and Research Center of Heart, Brain, Hormone, and Healthy Aging, University of Hong Kong, Hong Kong, China.

The antidiabetic hormone adiponectin circulates in blood as several oligomeric complexes, and the ratios between them are critical in determining insulin sensitivity. In this study we investigated the role of testosterone in regulating the oligomeric complex distribution of adiponectin. Gel filtration analysis revealed that circulating adiponectin existed as the forms of high molecular weight (HMW), middle molecular weight, and low molecular weight complexes in both human and mice. The concentration of HMW adiponectin in female was significantly higher than that in male, whereas there were no gender differences for the other two forms. Castration induced a dramatic elevation of the HMW form but had no effect on either the middle molecular weight or the low molecular weight form in mice. Testosterone treatment, on the other hand, caused a specific reduction of HMW adiponectin in the circulation. Pulse-chase labeling experiments in rat adipocytes revealed that the three oligomeric forms of adiponectin were secreted into the culture medium at different rates and that testosterone selectively impeded the secretion of HMW adiponectin but not the other two forms. The inhibitory effect of testosterone on secretion of HMW adiponectin was largely restored by the transcription inhibitor actinomycin D, suggesting the involvement of a transcriptional event in this process. The selective inhibition of HMW adiponectin by testosterone might contribute to the sex dimorphism of adiponectin in terms of its oligomeric complex distribution and could partly explain why men have higher risk to insulin resistance and atherosclerosis than women.
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http://dx.doi.org/10.1074/jbc.M414231200DOI Listing
May 2005