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Dong B.,Qilu Hospital | Dong B.,Shandong University | Yu Q.T.,Qilu Hospital | Yu Q.T.,Peoples Hospital of Huangpi District | And 16 more authors.
Journal of the American College of Cardiology | Year: 2012

Objectives: The aim of this study was to test the hypothesis that angiotensin (Ang)-converting enzyme-2 (ACE2) overexpression may inhibit myocardial collagen accumulation and improve left ventricular (LV) remodeling and function in diabetic cardiomyopathy. Background: Hyperglycemia activates the renin-Ang system, which promotes the accumulation of extracellular matrix and progression of cardiac remodeling and dysfunction. Methods: Ninety male Wistar rats were divided randomly into treatment (n = 80) and control (n = 10) groups. Diabetes was induced in the treatment group by a single intraperitoneal injection of streptozotocin. Twelve weeks after streptozotocin injection, rats in the treatment group were further divided into adenovirus-ACE2, adenovirusenhanced green fluorescent protein, losartan, and mock groups (n = 20 each). LV volume; LV systolic and diastolic function; extent of myocardial fibrosis; protein expression levels of ACE2, Ang-converting enzyme, and Ang-(1-7); and matrix metalloproteinase2 activity were evaluated. Cardiac myocyte and fibroblast culture was performed to assess Ang-II and collagen protein expression before and after ACE2 gene transfection. Results: Four weeks after ACE2 gene transfer, the adenovirus-ACE2 group showed increased ACE2 expression, matrix metalloproteinase2 activity, and LV ejection fractions and decreased LV volumes, myocardial fibrosis, and ACE, Ang-II, and collagen expression in comparison with the adenovirusenhanced green fluorescent protein and control groups. ACE2 was superior to losartan in improving LV remodeling and function and reducing collagen expression. The putative mechanisms may involve a shift in balance toward an inhibited fibroblast-myocyte cross-talk for collagen and transforming growth factorbeta production and enhanced collagen degradation by matrix metalloproteinase2. Conclusions: ACE2 inhibits myocardial collagen accumulation and improves LV remodeling and function in a rat model of diabetic cardiomyopathy. Thus, ACE2 provides a promising approach to the treatment of patients with diabetic cardiomyopathy. © 2012 American College of Cardiology Foundation.

Feng H.,University of Kentucky | Feng H.,Shandong University | Guo L.,University of Kentucky | Wang D.,Shandong University | And 7 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2011

Objective-: Scavenger receptor BI (SR-BI) is a high-density lipoprotein (HDL) receptor. Recent studies revealed that SR-BI protects against sepsis via modulating innate immunity. However, its role in adaptive immunity is unclear. Methods and Results-: SR-BI-null mice exhibited impaired lymphocyte homeostasis as shown by splenomegaly and imbalanced expansion of T and B lymphocytes in the spleens. Importantly, the activated T and B lymphocytes were increased 3-to 4-fold, indicating a heightened active status of T and B lymphocytes. More importantly, in line with the accumulation of the activated T and B lymphocytes, SR-BI-null mice developed systemic autoimmune disorders characterized by the presence of autoantibodies in circulation, the deposition of immune complexes in glomeruli, and the leukocyte infiltration in kidney. Further analyses revealed that SR-BI deficiency enhanced lymphocyte proliferation, caused imbalanced interferon-γ and interleukin-4 production in lymphocytes, and caused elevated inflammatory cytokine production in macrophages. Furthermore, HDL from SR-BI-null mice exhibited less capability of suppressing lymphocyte proliferation. Conclusion-: SR-BI regulates lymphocyte homeostasis, likely through its roles in modulating the proliferation of lymphocytes, the cytokine production by lymphocytes and macrophages, and the function of HDL. Its deficiency leads to impaired lymphocyte homeostasis and autoimmune disorders. Our findings reveal a previously unrecognized role of SR-BI in adaptive immunity. © 2011 American Heart Association. All rights reserved.

Zhang Y.,QiLu Hospital | Lv Y.,QiLu Hospital | Zhang Y.,Shandong Jining No1 Peoples Hospital | Gao H.,QiLu Hospital
PLoS ONE | Year: 2014

p53 is possibly the most important mammalian tumor suppressor and it is mutated or lost in more than half of all human cancers. The stability of p53 is primarily determined by the RING domain E3 ubiquitin ligase Hdm2, which targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation. UBE4B has been shown to physically interact with p53 and Hdm2 and to negatively regulate p53 stability and function. However, no one has determined whether UBE4B promotes p53 degradation in breast cancer. In this study, UBE4B promoted the degradation and ubiquitination of p53 to inhibit the apoptosis of cancer cells and promote tumorigenesis. Our results indicate that UBE4B regulates p53 in breast cancer and could be a viable target for developing new therapeutic strategies for breast cancer treatment. © 2014 Zhang et al.

Wang L.,Qilu Hospital | Dong Z.,Qilu Hospital | Huang B.,Qilu Hospital | Zhao B.,Shandong University | And 6 more authors.
Autophagy | Year: 2010

Macroautophagy (referred to as autophagy) is an evolutionarily conserved, bulk-destruction process in eukaryotes. During this process, the cytoplasm containing long-lived proteins and organelles is engulfed into double-membrane autophagosomes, and ultimately undergoes enzymatic degradation within lysosomes. Autophagy serves as a prosurvival machinery, or it may contribute to cell death. Accumulating evidence indicates that autophagy is involved in the pathogenesis and intervention of various human diseases. Pharmacological autophagy modulators are arousing interest from biologists and clinical physicians in light of their potential for disease therapy and increasing our understanding of the mechanism of autophagy. In this study, we identified two autophagy enhancers, 6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine (ABO) and 6,8-dichloro-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine (DBO), in human umbilical vein endothelial cells (HUVEC s) by autophagy assays, and demonstrate that ABO and DBO could stimulate autophagy in an mtor-independent and mtor-dependent manner, respectively; ABO-stimulated autophagy was attributed to the elevation of the Ca2+ channel annexin A7 (ANXA7), whereas DBO's effect was due to the level of intracellular reactive oxygen species (ROS). Importantly, we found that ANXA7 was essential for autophagy induction via modulating the intracellular calcium concentration ([Ca2+] i) in HUVEC s. In summary, our work introduced two distinct autophagy enhancers and highlighted the critical role of ANXA7 in endothelial autophagy. © 2010 Landes Bioscience.

Teng Y.,Qilu Hospital | Wang X.,Qilu Hospital | Wang Y.,Qilu Hospital | Ma D.,Qilu Hospital
Biochemical and Biophysical Research Communications | Year: 2010

Wnt/β-catenin signaling plays an important role not only in cancer, but also in cancer stem cells. In this study, we found that β-catenin and OCT-4 was highly expressed in cisplatin (DDP) selected A549 cells. Stimulating A549 cells with lithium chloride (LiCl) resulted in accumulation of β-catenin and up-regulation of a typical Wnt target gene cyclin D1. This stimulation also significantly enhanced proliferation, clone formation, migration and drug resistance abilities in A549 cells. Moreover, the up-regulation of OCT-4, a stem cell marker, was observed through real-time PCR and Western blotting. In a reverse approach, we inhibited Wnt signaling by knocking down the expression of β-catenin using RNA interference technology. This inhibition resulted in down-regulation of the Wnt target gene cyclin D1 as well as the proliferation, clone formation, migration and drug resistance abilities. Meanwhile, the expression of OCT-4 was reduced after the inhibition of Wnt/β-catenin signaling. Taken together, our study provides strong evidence that canonical Wnt signaling plays an important role in lung cancer stem cell properties, and it also regulates OCT-4, a lung cancer stem cell marker. © 2010 Elsevier Inc. All rights reserved.

To evaluate the application of pathological diagnosis by rapid paraffin sections in the diagnosis and treatment of cervical diseases. A total of 176 cases from our hospital between September 2009 and January 2010 with abnormal cervical cancer screening (including abnormal cytology result and high-risk HPV continuous positive) were randomly divided into 2 groups. Eighty-seven cases of them whose biopsy were got by Belinson forceps under the direction of colposcopy with rapid paraffin sections by ultrasonic histopathological rapid processor and BT transparent agents were selected as group A, while 89 cases with conventional paraffin sections were selected as group B. The production time and quality for paraffin sections were analyzed in the two groups. Those diagnosed as cervical intraepithelial neoplasia (CIN) II or even worse and some special patients with CINI in the two groups received surgery, including loop electrosurgical procedure (LEEP), cold knife conization (CKC), hysterectomy or radical hysterectomy. Tissue obtained after surgery was sent for routine pathological examination. If the results of postoperative routine pathological examination were inconsistent with the rapid or routine biopsy pathological examination, the heavier results were regard as the final diagnoses. The pathological results and diagnose accordance rates were recorded and compared between group A and group B. The quality of sections in two groups were all satisfied or basically satisfied to meet the diagnostic requirements. There were statistically significant difference in average production time between group A and B (40 minutes vs 24 hours, P<0.05). Thirty patients in group A and 32 patients in group B received surgery. The coincidence rate of biopsy pathological results and final diagnoses were 93% (28/30) for group A and 91% (29/32) for group B, in which there were not statistically significant difference (P>0.05). Rapid paraffin sections technology is safe, accurate and economical for rapid pathological diagnosis of cervical diseases, which is worthy for being widely used in hospitals.

Fang Q.,Shandong University | Zhao H.,Shandong University | Wang A.,Qilu Hospital | Gong Y.,Shandong University | Liu Q.,Shandong University
BMC Medical Genetics | Year: 2011

Background: Genome-wide association studies of asthma have identified a novel region containing ORMDL3 at chromosome 17q21 that is strongly associated with childhood-onset asthma and significantly linked to ORMDL3 transcript abundance. These results have been successfully replicated in childhood-onset asthma cohorts in several ethnic groups. In this study, we aimed to evaluate the association of polymorphisms in ORMDL3, GSDMB, ZPBP2 and IKZF3 and adult-onset asthma in a Chinese Han population.Methods: We genotyped 5 single nucleotide polymorphisms (SNPs) at chromosome 17q21 in 1,366 Han Chinese people comprising 710 patients with adult-onset asthma and 656 healthy controls. We compared the 2 groups in terms of allele and haplotype frequencies. Transcript levels were measured in leukocytes from 61 asthma patients by quantitative real-time PCR.Results: We found the 5 SNPs significantly associated with asthma (P<0.05), of which 2, rs11557467 and rs9303277, were strongly associated (P<0.001). Subjects carrying the G allele of rs11557467 or the C allele of rs9303277 showed increased risk of asthma (odds ratio [OR] 1.27, 95% confidence interval 1.07-1.51, P = 0.006, and OR 1.27, 1.07-1.49, P = 0.005, respectively), even after adjusting for age and sex. The risk of asthma was lower for carriers of the haplotype CTGTT (OR 0.81, 0.67-0.97, P = 0.02). The risk allele for each SNP was associated with increased expression of ORMDL3 and GSDMB in leukocytes (all p<0.05).Conclusions: Our replication study suggests that variants in 17q21 are significantly associated with risk of adult-onset asthma and gene expression in a Chinese Han population. © 2011 Fang et al; licensee BioMed Central Ltd.

Chen X.,Qilu Hospital | Fan R.,City University of Hong Kong
Journal of Medicine and Philosophy | Year: 2010

This essay illustrates what the Chinese family-based and harmony-oriented model of medical decision making is like as well as how it differs from the modern Western individual-based and autonomy-oriented model in health care practice. The essay discloses the roots of the Chinese model in the Confucian account of the family and the Confucian view of harmony. By responding to a series of questions posed to the Chinese model by modern Western scholars in terms of the basic individualist concerns and values embedded in the modern Western model, we conclude that the Chinese people have justifiable reasons to continue to apply the Chinese model to their contemporary health care and medical practice. © The Author 2010. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved.

Zhang Q.,Qilu Hospital | Jiang F.,Qilu Hospital
BMC neurology | Year: 2014

RESULTS: As compared to normal arteries, we identified 157 microRNAs that were differentially expressed in the aneurysmal tissue (P < 0.05 and fold change ≥ 2), including 72 upregulated and 85 downregulated. The changed microRNAs included endothelium-enriched microRNAs such as members of the let-7 family, miR-17, miR-23b, miR-126, hsa-miR-24-1 and miR-222, and vascular smooth muscle-enriched miRNAs such as miR-143 and miR-145. Moreover, miR-1, miR-10a, miR-125b, and miR-26a, which were implicated in modulating vascular smooth muscle cell functions such as proliferation, apoptosis and shift of phenotype, were also changed. In contrast, microRNAs involved in monocyte and macrophage functions, such as miR-155, miR-146a, miR-223, and miR-124a, were not significantly changed. Bioinformatic analysis revealed that the changed microRNAs were associated with several biological processes related to aneurysm formation, including inflammation, dysregulation of extracellular matrix, smooth muscle cell proliferation, programmed cell death, and response to oxidative stress. Interestingly, we found that a subset of the potential microRNA target genes belonged to the protein translation machinery, including various eukaryotic translation initiation factors and ribosomal proteins, and this finding was highly correlated with our previous transcriptome data showing that multiple genes of the ribosomal proteins and translation initiation and elongation factors were significantly downregulated in human intracranial aneurysms.CONCLUSIONS: Our results support that dysregulated microRNAs may have a pathogenic role in intracranial aneurysms. Disruption of the protein translation process may have a pathogenic role in the development of intracranial aneurysms.METHODS: Genome-wide microRNA screening was performed in 6 intracranial aneurysmal samples and 6 normal superficial temporal arteries. Each case and control pair was individually matched with gender, age (±5 years), and high blood pressure history. Microarray analysis was performed using Agilent Human miRNA arrays.BACKGROUND: Intracranial aneurysms are pathological dilatations of the cerebral artery, while rupture of intracranial aneurysms causes life-threatening subarachnoid hemorrhage. The molecular mechanisms of pathogenesis of intracranial aneurysms are poorly understood. MicroRNAs have fundamental roles in modulating vascular biology and disease. In the present study, we carried out a genome-wide characterization on expressions of microRNAs, and performed integrative analyses in conjunction with changes of the transcriptome in human intracranial aneurysms.

Liu Y.,Qilu Hospital
Zhonghua yi xue za zhi | Year: 2014

OBJECTIVE: To explore the clinical characteristics, efficacy and prognosis of primary extradural meningiomas (PEMs) in head.METHODS: A total of 19 treated surgically case of PEMs at Qilu Hospital, Shandong University between May 1994 and December 2012 were analyzed retrospectively with respects to their demographic features, presenting symptoms & duration, tumor location & type, imaging features, surgical results, pathological grade, histological subtype and follow-up outcomes.RESULTS: PEMs in head accounted for 1.2% of all meningiomas in this group. The male-to-female ratio was 1: 0.7. The mean age was 36.6 years with a bimodal distribution of age. The common presenting symptoms included nasal obstruction and a painless and gradually expanding mass in the region of lesion. The average duration of symptom was 3.07 years. The skull convexities, paranasal sinuses and nasal cavity, orbit and epidural space were common tumor sites. The most common type was typeII. The rate of total tumor removal was 100%. And no perioperative mortality occurred in this series. Benign and atypical meningiomas accounted for 94.7% and 6.3% respectively. Meningothelial and psammomatous meningiomas were common histopathological subtypes. There was one case of tumoral recurrence. And no mortality was reported during a mean follow-up period of 2.43 (0.25-8.5) years.CONCLUSION: PEMs in head have some marked clinical characteristics compared with primary intradural meningiomas. Total tumor removal together with a wide excision of all involved tissue followed by the reconstruction of tissue defects is the best surgical option. The prognosis is excellent in most cases after complete resection.

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