Tangdu Hospital

Xi’an, China

Tangdu Hospital

Xi’an, China

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(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.

Wang Q.,Tangdu Hospital | Zhao H.,Tangdu Hospital | Chen W.,First Peoples Hospital | Li N.,First Peoples Hospital | Wan Y.,PLA Fourth Military Medical University
Blood Pressure Monitoring | Year: 2014

OBJECTIVE: The aim of this study was to validate the iHealth BP7 wireless wrist blood pressure monitor according to the European Society of Hypertension International Protocol (ESH-IP) revision 2010. MATERIALS AND METHODS: A total of 99 pairs of test device and reference blood pressure measurements (three pairs for each of the 33 participants) were obtained for validation. The ESH-IP revision 2010 for the validation of blood pressure measuring devices in adults was followed precisely. RESULTS: The device produced 66, 87, and 97 measurements within 5, 10, and 15 mmHg for systolic blood pressure (SBP) and 72, 93, and 99 mmHg for diastolic blood pressure (DBP), respectively. The mean±SD device-observer difference was -0.7±6.9 mmHg for SBP and -1.0±5.1 mmHg for DBP. The number of participants with two or three device-observer differences within 5 mmHg was 25 for SBP and 26 for DBP; furthermore, there were three participants for SBP and one participant for DBP, with none of the device-observer differences within 5 mmHg. CONCLUSION: On the basis of the validation results, the iHealth BP7 wireless wrist blood pressure monitor can be recommended for self-measurement in an adult population. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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.

Cui G.-B.,Tangdu Hospital | An J.-Z.,PLA Fourth Military Medical University | Zhang N.,PLA Fourth Military Medical University | Zhao M.-G.,PLA Fourth Military Medical University | And 2 more authors.
Molecular Pain | Year: 2012

Background: Interleukin-8 (IL-8) is known for its roles in inflammation and plays critical roles in the development of pain. Its expression increases in the brain after peripheral inflammation. Prefrontal cortex, including the anterior cingulate cortex (ACC), is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission, however, little is known about the expression of IL-8 and its role in the enhanced ACC synaptic transmission in animals with persistent inflammatory pain.Findings: In the present study, we examined IL-8 expression in the ACC, somatosensory cortex (SSC), and the dorsal horn of lumbar spinal cord following hind-paw administration of complete Freund's adjuvant (CFA) in mice and its effects on the ACC synaptic transmission. Quantification of IL-8 at protein level (by ELISA) revealed enhanced expression in the ACC and spinal cord during the chronic phases of CFA-induced peripheral inflammation. In vitro whole-cell patch-clamp recordings revealed that IL-8 significantly enhanced synaptic transmission through increased probability of neurotransmitter release in the ACC slice. ACC local infusion of repertaxin, a non-competitive allosteric blocker of IL-8 receptors, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in mice.Conclusions: Our findings suggest that up-regulation of IL-8 in the ACC partly attributable to the enhanced prefrontal synaptic transmission in the mice with persistent inflammatory pain. © 2012 Cui et al; licensee BioMed Central Ltd.

Jiang K.,Tangdu Hospital
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2011

To construct, express and purify a human fusion protein, which is composed of a single-chain antibody fragment scFv that recognizes HER2 protein and an oligo-9-arginine, and to analyze the binding activity of the expressed fusion protein. Pairs of oligonucleotide primers were designed and used to amplify the scFv-9R. The fusion protein gene scFv-9R was then cloned into expression vector pQE30 and expressed in E.coli M15.Expressed protein was detected by SDS-PAGE and Western blot and purified by Ni-NTA chelating agarose. Then, the purified protein was refolded by dialysis and concentrated by ultrafiltration. The antigen-binding activity of the scFv-9R fusion protein was confirmed by ELISA, and the siRNA binding ability was confirmed by electrophoretic mobility shift assay (EMSA). HER2 scFv-9R encoding sequence was correctly cloned into the expression vector. The recombinant protein was insolubly expressed in E.coli M15 induced by IPTG. ELISA confirmed that it had specific antigen binding activity; EMSA assured that it had siRNA binding activity. The scFv-9R fusion protein can specially bind with both HER2 antigen and siRNA.

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.

Wang H.-T.,Tangdu Hospital | Li Z.-L.,Tangdu Hospital | Fan B.-Y.,Tangdu Hospital | Su F.-F.,Tangdu Hospital | And 3 more authors.
Journal of Thoracic and Cardiovascular Surgery | Year: 2014

Objective The major atrial ganglionated plexi (GP) can initiate atrial fibrillation alone without any contribution from the extrinsic cardiac nervous system. However, if stimulation of the ventricular GP, especially the aortic root GP, can provoke atrial fibrillation (AF) alone is unknown. Our study was designed to investigate the independent role of aortic root GP activity in the initiation of AF. Methods In 10 Langendorff-perfused canine hearts, the atrial effective refractory period, pulmonary vein effective refractory period, and percentage of AF induced were measured at baseline and during aortic root GP stimulation. Results Stimulation of the aortic root GP shortened the atrial effective refractory period from 128 ± 10 ms at baseline to 103 ± 15 ms (P <.05) and shortened the pulmonary vein effective refractory period from 139 ± 14 ms to 114 ± 15 ms (P <.05). Furthermore, the percentage of AF induced in the 10 isolated hearts increased from 10% at baseline to 90% during aortic root GP stimulation (P <.05). Conclusions In Langendorff-perfused canine hearts, stimulation of the aortic root GP provokes AF in the absence of any extrinsic cardiac nerve activity. The aortic root GP is an important element in the intrinsic neuronal loop that can increase the risk of AF in isolated heart models. © 2014 by The American Association for Thoracic Surgery.

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