Zhang T.,Northwestern University |
Zhang T.,University of Georgia |
Guo L.,Northwestern University |
Li K.,Northwestern University |
And 7 more authors.
Cerebral Cortex | Year: 2012
Studying structural and functional connectivities of human cerebral cortex has drawn significant interest and effort recently. A fundamental and challenging problem arises when attempting to measure the structural and/or functional connectivities of specific cortical networks: how to identify and localize the best possible regions of interests (ROIs) on the cortex? In our view, the major challenges come from uncertainties in ROI boundary definition, the remarkable structural and functional variability across individuals and high nonlinearities within and around ROIs. In this paper, we present a novel ROI prediction framework that localizes ROIs in individual brains based on their learned fiber shape models from multimodal task-based functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data. In the training stage, shape models of white matter fibers are learnt from those emanating from the functional ROIs, which are activated brain regions detected from task-based fMRI data. In the prediction stage, functional ROIs are predicted in individual brains based only on DTI data. Our experiment results show that the average ROI prediction error is around 3.94 mm, in comparison with benchmark data provided by working memory and visual task-based fMRI. Our work demonstrated that fiber bundle shape models derived from DTI data are good predictors of functional cortical ROIs. © The Author 2011. Published by Oxford University Press.
Li K.,Northwestern Polytechnical University |
Li K.,University of Georgia |
Guo L.,Northwestern Polytechnical University |
Li G.,Northwestern Polytechnical University |
And 6 more authors.
NeuroImage | Year: 2010
Folding is an essential shape characteristic of the human cerebral cortex. Descriptors of cortical folding patterns have been studied for decades. However, many previous studies are either based on local shape descriptors such as curvature, or based on global descriptors such as gyrification index or spherical wavelets. This paper proposes a gyrus-scale folding pattern analysis technique via cortical surface profiling. Firstly, we sample the cortical surface into 2D profiles and model them using a power function. This step provides both the flexibility of representing arbitrary shape by profiling and the compactness of representing shape by parametric modeling. Secondly, based on the estimated model parameters, we extract affine-invariant features on the cortical surface, and apply the affinity propagation clustering algorithm to parcellate the cortex into cortical regions with strict hierarchy and smooth transitions among them. Finally, a second-round surface profiling is performed on the parcellated cortical surface, and the number of hinges is detected to describe the gyral folding pattern. We have applied the surface profiling method to two normal brain datasets and a schizophrenia patient dataset. The experimental results demonstrate that the proposed method can accurately classify human gyri into 2-hinge, 3-hinge and 4-hinge patterns. The distribution of these folding patterns on brain lobes and the relationship between fiber density and gyral folding patterns are further investigated. Results from the schizophrenia dataset are consistent with commonly found abnormality in former studies by others, which demonstrates the potential clinical applications of the proposed technique. © 2010 Elsevier Inc.
Feng B.,PLA Fourth Military Medical University |
Xing J.-H.,PLA Fourth Military Medical University |
Jia D.,Tangdu Hospital |
Liu S.-B.,PLA Fourth Military Medical University |
And 4 more authors.
Behavioural Brain Research | Year: 2011
Investigating the interaction between nicotinic and opioid receptors is of great interest for both basic mechanistic and clinical reasons. Morphine and nicotine, two common drugs of abuse, share several behavioral and rewarding properties. However, little is known about the subtypes of nicotinic acetylcholine receptors (nAChR) in the reinstatement of morphine-induced conditioned place preference (CPP). In this study, we found that a non-specific nAChR agonist, nicotine (0.5mg/kg), had no effects on the reinstatement of morphine-induced CPP. However, we found that pretreatment with specific α4β2 and α7 nAChR subtype antagonists, dihydroxy-β-erithroidine (DHβE, 5mg/kg) and methyllycaconitine (MLA, 4mg/kg), 20min prior to administration of morphine, inhibited the reinstatement of morphine-induced CPP by drug priming in mice. Furthermore, depression of the reinstatement of morphine-induced CPP by a single DHβE or MLA treatment lasted at least three days later when the reinstatement was induced by morphine priming. The data suggest that specific nAChR subtypes, i.e., α4β2 and α7, may contribute to the reinstatement of morphine-induced CPP by drug priming in mice. © 2011 Elsevier B.V.
Zhao L.,PLA Fourth Military Medical University |
Liu H.,PLA Fourth Military Medical University |
Yue L.,PLA Fourth Military Medical University |
Zhang J.,PLA Fourth Military Medical University |
And 5 more authors.
Molecular Neurobiology | Year: 2017
Melatonin (Mel) has been reported to alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH). The activation of silent information regulator 1 (Sirt1), a histone deacetylase, has been suggested to be beneficial in SAH. However, the precise role of Sirt1 in Mel-mediated protection against EBI following SAH has not been elucidated. The present study aims to evaluate the role of melatonin receptor/Sirt1/nuclear factor-kappa B (NF-κB) in this process. The endovascular perforation SAH model was used in male C57BL/6J mice, and melatonin was administrated intraperitoneally (150 mg/kg). The mortality, SAH grade, neurological score, brain water content, and neuronal apoptosis were evaluated. The expression of Sirt1, acetylated-NF-κB (Ac-NF-κB), Bcl-2, and Bax were detected by western blot. To study the underlying mechanisms, melatonin receptor (MR) antagonist luzindole and Sirt1 small interfering RNA (siRNA) were administrated to different groups. The results suggest that Mel improved the neurological deficits and reduced the brain water content and neuronal apoptosis. In addition, Mel enhanced the expression of Sirt1 and Bcl-2 and decreased the expression of Ac-NF-κB and Bax. However, the protective effects of Mel were abolished by luzindole or Sirt1 siRNA. In conclusion, our results demonstrate that Mel attenuates EBI following SAH via the MR/Sirt1/NF-κB signaling pathway. © 2016, Springer Science+Business Media New York.
News Article | November 17, 2016
(Philadelphia, PA) - The inability of cells to eliminate damaged proteins and organelles following the blockage of a coronary artery and its subsequent re-opening with angioplasty or medications - a sequence known as ischemia/reperfusion - often results in irreparable damage to the heart muscle. To date, attempts to prevent this damage in humans have been unsuccessful. According to a new study by scientists at the Lewis Katz School of Medicine at Temple University (LKSOM), however, it may be possible to substantially limit reperfusion injury by increasing the expression of a protein known as Bcl-2-associated athanogene 3 (BAG3). "We found that BAG3 plays a pivotal role in protecting the heart from damage caused by reperfusion injury," explained the study's lead author, Feifei Su, MD, PhD, a postdoctoral fellow in the laboratory of Arthur M. Feldman, MD, PhD, Professor of Medicine at LKSOM. Ischemia impairs the function of cellular organelles including mitochondria, the cell's energy-producers, resulting in harmful effects that set the stage for a sudden burst in the generation of toxic oxidizing substances when oxygenated blood reenters the heart. The toxins lead to fundamental changes in the biology of the heart. Notably, they activate cell death pathways and decrease autophagy - the process by which cells remove malfunctioning proteins and organelles. Autophagy plays a critical role in removing damaged myocardial cells (the muscular tissue of the heart) and misfolded heart muscle fibers. The new work shows that BAG3 expression both inactivates cell death pathways, helping prevent the loss of heart cells triggered by ischemia, and activates autophagy, thereby enabling cells to clear out impaired components of the heart cell before they inflict extensive damage. The findings, published online November 17 in the journal JCI Insight, open the door to the investigation of BAG3 as a therapeutic target during reperfusion in heart attack patients. In initial work, the research group found that BAG3 promotes autophagy and inhibits programmed cell death (apoptosis) in cultured cardiac myocytes. Subsequently, they found that when heart cells were exposed to the stress of hypoxia/reoxygenation or when living mice were stressed with ischemia/reperfusion, they suffered dramatic reductions in BAG3 expression. Those paradoxical changes in BAG3 levels turned out to be directly associated with increases in biomarkers of autophagy and with decreases in biomarkers of apoptosis. By artificially knocking down BAG3 in mouse heart cells, the researchers were able to produce an apoptosis-autophagy biomarker phenotype nearly identical to that produced by hypoxia/reoxygenation. By contrast, BAG3 overexpression normalized apoptosis and autophagy. In a key experiment, the Temple team further showed that tissue damage sustained following ischemia/reperfusion could be substantially reduced by treating mice with BAG3 prior to vessel re-opening. BAG3 overexpression before the onset of ischemia/reperfusion also resulted in normalization in apoptosis and autophagy biomarkers. According to Dr. Feldman, the senior investigator on the project, his team's interest in the role of BAG3 in the heart has grown in recent years, owing to their discovery of a unique BAG3 mutation in a family with familial dilated cardiomyopathy, a genetic condition characterized by the development of heart failure between early and late adulthood. "After finding that a mutation in BAG3 caused heart failure in a Philadelphia family, we have been trying to figure out what the protein does in the heart," Dr. Feldman said. "Now that we have a better understanding of its role and what happens when its levels are increased, we can investigate the possibility of targeting BAG3 in human patients using gene therapy or a small molecule." Other researchers on the new study include Feifei Su in the Department of Medicine at LKSOM, Temple University, and the Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China; Valerie D. Myers in the Department of Medicine at LKSOM, Temple University; Tijana Knezevic, Farzaneh G. Tahrir, Manish K. Gupta, Jennifer Gordon, and Kamel Khalili in the Department of Neuroscience at LKSOM, Temple University; JuFang Wang, Ehre Gao, Muniswamy Madesh, Joseph Rabinowitz, Douglas G. Tilley, and Joseph Y. Cheung in the Center for Translational Medicine at LKSOM, Temple University; and Frederick V. Ramsey in the Department of Clinical Sciences at LKSOM, Temple University. The research was supported by National Institutes of Health grants P01 HL 091799-01 and R01 HL123093. Temple University Health System (TUHS) is a $1.6 billion academic health system dedicated to providing access to quality patient care and supporting excellence in medical education and research. The Health System consists of Temple University Hospital (TUH), ranked among the "Best Hospitals" in the region by U.S. News & World Report; TUH-Episcopal Campus; TUH-Northeastern Campus; Fox Chase Cancer Center, an NCI-designated comprehensive cancer center; Jeanes Hospital, a community-based hospital offering medical, surgical and emergency services; Temple Transport Team, a ground and air-ambulance company; and Temple Physicians, Inc., a network of community-based specialty and primary-care physician practices. TUHS is affiliated with the Lewis Katz School of Medicine at Temple University. The Lewis Katz School of Medicine (LKSOM), established in 1901, is one of the nation's leading medical schools. Each year, the School of Medicine educates approximately 840 medical students and 140 graduate students. Based on its level of funding from the National Institutes of Health, the Katz School of Medicine is the second-highest ranked medical school in Philadelphia and the third-highest in the Commonwealth of Pennsylvania. According to U.S. News & World Report, LKSOM is among the top 10 most applied-to medical schools in the nation. Temple Health refers to the health, education and research activities carried out by the affiliates of Temple University Health System (TUHS) and by the Katz School of Medicine. TUHS neither provides nor controls the provision of health care. All health care is provided by its member organizations or independent health care providers affiliated with TUHS member organizations. Each TUHS member organization is owned and operated pursuant to its governing documents.
He J.,PLA Fourth Military Medical University |
Huan Y.,PLA Fourth Military Medical University |
Qiao Q.,Tangdu Hospital |
Zhang J.,PLA Fourth Military Medical University |
Zhang J.S.,PLA Fourth Military Medical University
Clinical Radiology | Year: 2014
Aim The purpose of the present study was to summarize the computed tomography (CT) features of renal carcinomas associated with Xp11.2 translocations, and determine whether the diagnosis can be reliably deduced from imaging findings. Materials and methods Radiological studies of six patients (aged from 9-29 years) with renal carcinoma associated with Xp11.2 translocations were retrospectively analysed. Results The tumours varied in size from 3.3-11 cm (mean 5.4 cm). Unenhanced CT and cortical, medullary, and pelvic-phase contrast-enhanced CT imaging was undertaken in all cases. Unenhanced CT revealed that tumours had a relatively increased radiodensity (4/6, ranged from 45-60 HU) and suggested the possibility of diffuse haemorrhage. Three of the six cases showed irregular and boundary calcification of the lesion. Contrast-enhanced CT showed relatively well demarcated tumours with heterogeneous enhancement (6/6). Prolonged enhancement of tumours might be a common sign (6/6) in Xp11.2 translocations. Three out of the six cases were combined with retroperitoneal lymph nodes metastasis. Conclusion Renal carcinomas associated with Xp11.2 translocations should be considered, particularly in children and young patients, when the lesion has calcification and is hyper-dense on unenhanced CT, and has prolonged enhancement on contrast-enhanced images. © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Zhou F.,Tangdu Hospital |
He X.,Tangdu Hospital |
Liu H.,PLA Fourth Military Medical University |
Zhu Y.,Yale University |
And 7 more authors.
Cancer | Year: 2012
Background: Previous studies have demonstrated that circadian genes play a role in the development and progression of many cancers. This study aims to assess the effects of single nucleotide polymorphisms (SNPs) in circadian genes on recurrence and survival of colorectal cancer (CRC) patients. Methods: Nine functional SNPs in 3 genes (CLOCK, NPAS2, and BMAL1) on the circadian positive feedback loop were selected and genotyped using the Sequenom iPLEX genotyping system in a cohort of 411 resected Chinese CRC patients. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. Results: The authors identified 2 SNPs in the CLOCK gene to be significantly associated with CRC overall survival. SNP rs3749474 exhibited a significant association with survival of CRC patients in the additive model (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.37-0.81; P =.003). In addition, patients carrying the heterozygous variant of rs1801260 had significantly increased overall survival compared with those carrying homozygous wild-type genotype (HR, 0.31; 95% CI, 0.11-0.88; P =.03). Findings from functional assay provided further biological support for these significant associations. Stratified analysis found no modifying effect of chemotherapy on the prognostic significance of both SNPs. Moreover, we observed cumulative effects of these 2 SNPs on CRC overall survival (P for trend =.01). Compared with patients carrying no unfavorable genotypes, those carrying 2 unfavorable genotypes had a 2.92-fold increased risk of death (P =.03). Conclusions: The results suggest for the first time that CLOCK gene polymorphisms may serve as an independent prognostic marker for CRC patients. © 2011 American Cancer Society.
Ma R.,PLA Fourth Military Medical University |
Li M.,Tangdu Hospital |
Luo J.,PLA Fourth Military Medical University |
Yu H.,PLA Fourth Military Medical University |
And 3 more authors.
Biomaterials | Year: 2013
Decellularization techniques have been widely used as an alternative strategy for organ reconstruction. However, the compliance of tracheal or laryngeal tissues can be increased during the decellularization process, which might cause postoperative stenosis due to elimination of chondrocytes. The purpose of our study was to construct a decellularized, whole, laryngeal scaffold with preserved chondrocytes using perfusion techniques and to evaluate the immunogenicity of the decellularized scaffold in vitro and in vivo in a rat model. The cellular components and immunogenicity of the scaffold were decellularized after 14 h of perfusion with detergent and 48 h of perfusion with phosphate buffered saline. However, the cartilage was well preserved via histological analysis and a chondrocyte viability test. Compared to the fresh larynx, the decellularized larynx did not show the presence of major histocompatibility complex antigens via immunohistochemical analysis in vitro and no significant immune rejection occurred 12 weeks post-implantation. In conclusion, decellularization via perfusion can achieve a decellularized, whole-laryngeal scaffold with the cell components removed and the cartilage and extra-cellular matrix well preserved. T cell-mediated immune rejection was significantly reduced in decellularized laryngeal cartilaginous scaffolds in vivo. © 2012 Elsevier Ltd.
Yang J.,Tangdu Hospital |
Cao Y.,PLA Fourth Military Medical University |
Sun J.,Tangdu Hospital |
Zhang Y.,PLA Fourth Military Medical University
Medical Oncology | Year: 2010
The medicinal properties of curcumin are well documented in Indian and Chinese systems of medicine, which refer to its wide use in the treatment of some diseases. It has shown to have anti-carcinogenic properties and is known to prevent tumor development in some cancers. In our study, we confirmed that the expression of miR-15a and miR-16 was upregulated and that of Bcl-2 was downregulated in curcumin-treated MCF-7 cells. Silencing miR-15a and miR-16 by specific inhibitors restored the expression of Bcl-2. Thus, we concluded that curcumin can reduce the expression of Bcl-2 by upregulating the expression of miR-15a and miR-16 in MCF-7 cells. © Humana Press Inc. 2009.
Li X.,Tangdu Hospital
BMJ case reports | Year: 2013
Cardiac rupture is a complication of myocardial infarction (MI) with extremely high mortality. Poor prognosis is usually predicted in conservatively treated patients. The treatment for cardiac rupture and thrombosis is in conflict. We reported an MI case of cardiac rupture and cerebral thrombosis using a conservative method. This case indicated that (1) It is noteworthy that patients suffering from the subacute form of rupture may remain haemodynamically stable. This type of patients may benefit from a conservative treatment without anticoagulation or antiplatelet at the onset of cardiac rupture. (2) Thirty days following cardiac rupture, it is safe to use warfarin anticoagulation for cerebral thrombosis treatment. The patient suffered from acute MI, cardiac rupture and subsequently cerebral thrombosis. We treated this patient in a conservative manner and the patient remained alive for 8 years. This case suggested that it may be safe to use warfarin anticoagulation treatment for cerebral thrombosis 30 days following cardiac rupture.