The Third Hospital of Jinan

Jinan, China

The Third Hospital of Jinan

Jinan, China
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Yang A.-Q.,The Third Hospital of Jinan | Chai Y.-Z.,The Third Hospital of Jinan | Song M.,Jinan Maternity and Child Care Hospital
Chinese Journal of Tissue Engineering Research | Year: 2016

BACKGROUND: Intrauterine device (IUD), widely used for contraception, achieves contraceptive effect by mechanical stimulation or chemical interference. Biological industry has been reported to have good performance and biocompatibility, but its effect used for IUD is rarely reported. OBJECTIVE: To explore the Contraceptive effect of biological ceramic IUDS. METHODS: Totally 90 female rats were randomly divided into three groups (n=30 per group). The biological ceramic IUD and the bare copper IUD were followed implanted into the middle of rat uterus, and blank control group received no intervention. One month later, according to the male and female ratio of 3: 1, 30 male mice were selected to mate With female rats in the three groups. At 14 days after mating, 10 female rats were randomly selected from each group to detect the number of embryos in the implanted side and the number of pregnant rats, and the contraceptive rate was calculated. Ten rats among The remaining rats in each group underwent removal surgery of IUD, and mated with male rats again. After 60 days, the remaining rats were sacrificed to observe the morphology of liver, kidney and uterus. RESULTS in the groups of biological ceramic and bare copper IUD was significantly lower than that in the blank control group (P < 0.05), and the contraceptive rate reached 100% in the former two groups. The number of uterine embryos of implanted side and pregnant rats, and fertility recovery rate in the blank control and biological ceramic IUD groups were significantly higher than those in the bare copper IUD group (P <0.05), but no significant differences were found between Blank culture and biological ceramic groups (P> 0.05). In the biological ceramic IUD group, there have mild Mland expansion, and visible some neutrophils both inside and outside the uterine cavity, but these buildings were milder compared with the bare copper IUD group. No abnormal changes occurred in the rat kidney and liver. These results show that the biological ceramic IUD and bare copper IUD both can obtain the desired contraceptive effect but Make no damage to the rat kidney and liver. Especially biological pump IUD holding excellent reversible recovery of fertility ability with less endometrial stimulation. © 2016, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.


Li Y.,The Third Hospital of Jinan | Ma X.,The Third Hospital of Jinan | Wang Y.,The Third Hospital of Jinan | Li G.,The Third Hospital of Jinan
Biomedicine and Pharmacotherapy | Year: 2017

microRNA-489 (miR-489), a newly identified tumor-related miRNA, functions as an oncogene or tumor suppressor via regulating growth and metastasis of human cancers. But, the clinical significance, biological function and underlying mechanisms of miR-489 in glioma remain rarely known. Here, we showed that the levels of miR-489 in glioma tissues were notably underexpressed compared to corresponding non-tumor tissues. In accordance, the relative levels of miR-489 were decreased in glioma cell lines compared with NHA cells. Kaplan-Meier plots indicated that miR-489 low expressing glioma patients showed a prominent shorter overall survival. In addition, miR-489 overexpression prohibited proliferation and cell cycle progression, and promoted apoptosis in U251 cells. While, miR-489 knockdown showed opposite effects on these cellular processes of U87 cells. In vivo experiments demonstrated that miR-489 restoration reduced the tumor volume and weight of subcutaneous glioma xenografts in nude mice. Notably, Spindlin 1 (SPIN1) was inversely and directly regulated by miR-489 in glioma cells. A negative correlation between the expression of miR-489 and SPIN1 mRNA was confirmed in glioma tissues. Interestingly, miR-489 inversely modulated activation of PI3K/AKT pathway and expression of downstream targets including p-mTOR, Cyclin D1 and BCL-XL. SPIN1 re-expression abolished the effects of miR-489 on U251 cells with enhanced activation of PI3K/AKT pathway and malignant phenotype. Meanwhile, AKT inhibitor MK-2206 blocked activation of PI3K/AKT pathway and resulted in reduced proliferation, cell cycle arrest and increased apoptosis in miR-489 down-regulating U87 cells. Altogether, our data support that miR-489 loss facilitates malignant phenotype of glioma cells probably via SPIN1-mediated PI3K/AKT pathway. © 2017 Elsevier Masson SAS


PubMed | Shanghai Fire Corps Hospital, The Third Hospital of Jinan, Shanghai JiaoTong University and Soochow University of China
Type: | Journal: Materials science & engineering. C, Materials for biological applications | Year: 2016

Posttraumatic tendon adhesion limits the motion of the limbs greatly. Biomimetic tendon sheaths have been developed to promote tendon healing and gliding. However, after introduction of these biomaterials, the associated inflammatory responses can decrease the anti-adhesion effect. Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) that can decrease inflammation responses. We blended hyaluronic acid and poly(l-lactic acid)-polyethylene glycol (PELA) with microgel electrospinning technology to form an inner layer of a bi-layer biomimetic sheath using sequential electrospinning of an outer celecoxib-PELA layer. Electrospun bi-layer fibrous membranes were mechanically tested and characterized by morphology, surface wettability, and drug release. The tensile strength showed a decreased trend and water contact angles were 114.7 3.9, 103.6 4.4, 116.3 5.1, 122.8 4.7, and 126.5 4.2 for the surface of PELA, hyaluronic acid-PELA, 2, 6, and 10% celecoxib-PELA electrospun fibrous membranes, respectively. In vitro drug release studies confirmed burst release and then sustained release from the fibrous membranes containing celecoxib for 20 days. In a chicken model of flexor digitorum profundus tendon surgery, the outer celecoxib/PELA layer offered advanced anti-adhesion roles compared to the outer PELA layer and the inner hyaluronic acid-loaded PELA layer still offered tendon healing and gliding. Thus, celecoxib-loaded anti-adhesive tendon sheaths can continuously offer bi-layer biomimetic tendon sheath effects with celecoxib release from the outer layer to prevent tendon adhesion.


PubMed | Guangzhou University of Chinese Medicine, the Third Hospital of Jinan and the First Peoples Hospital of Shangqiu
Type: | Journal: Drug design, development and therapy | Year: 2016

Estrogen receptors (ERs) are nuclear transcription factors that are involved in the regulation of many complex physiological processes in humans. ERs have been validated as important drug targets for the treatment of various diseases, including breast cancer, ovarian cancer, osteoporosis, and cardiovascular disease. ERs have two subtypes, ER- and ER-. Emerging data suggest that the development of subtype-selective ligands that specifically target ER- could be a more optimal approach to elicit beneficial estrogen-like activities and reduce side effects.Herein, we focused on ER- and developed its in silico quantitative structure-activity relationship models using machine learning (ML) methods.The chemical structures and ER- bioactivity data were extracted from public chemogenomics databases. Four types of popular fingerprint generation methods including MACCS fingerprint, PubChem fingerprint, 2D atom pairs, and Chemistry Development Kit extended fingerprint were used as descriptors. Four ML methods including Nave Bayesian classifier, k-nearest neighbor, random forest, and support vector machine were used to train the models. The range of classification accuracies was 77.10% to 88.34%, and the range of area under the ROC (receiver operating characteristic) curve values was 0.8151 to 0.9475, evaluated by the 5-fold cross-validation. Comparison analysis suggests that both the random forest and the support vector machine are superior for the classification of selective ER- agonists. Chemistry Development Kit extended fingerprints and MACCS fingerprint performed better in structural representation between active and inactive agonists.These results demonstrate that combining the fingerprint and ML approaches leads to robust ER- agonist prediction models, which are potentially applicable to the identification of selective ER- agonists.


PubMed | Affiliated Hospital of Jining Medical College, The Third Hospital of Jinan and Shandong University
Type: Journal Article | Journal: Oncotarget | Year: 2016

Prohibitin (PHB) is a highly conserved protein implicated in various cellular functions including proliferation, apoptosis, tumor suppression, transcription, and mitochondrial protein folding. However, its function in diabetic cardiomyopathy (DCM) is still unclear. In vivo, type 2 diabetic rat model was induced by using a high-fat diet and low-dose streptozotocin. Overexpression of the PHB protein in the model rats was achieved by injecting lentivirus carrying PHB cDNA via the jugular vein. Characteristics of type 2 DCM were evaluated by metabolic tests, echocardiography and histopathology. Rats with DCM showed severe insulin resistance, left ventricular dysfunction, fibrosis and apoptosis. PHB overexpression ameliorated the disease. Cardiofibroblasts (CFs) and H9c2 cardiomyoblasts were used in vitro to investigate the mechanism of PHB in altered function. In CFs treated with HG, PHB overexpression decreased expression of collagen, matrix metalloproteinase activity, and proliferation. In H9c2 cardiomyoblasts, PHB overexpression inhibited apoptosis induced by HG. Furthermore, the increased phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was significantly decreased and the inhibited phosphorylation of Akt was restored in DCM. Therefore, PHB may be a new therapeutic target for human DCM.


PubMed | The Third Hospital of Jinan and Shandong Provincial Hospital
Type: Journal Article | Journal: Genetics and molecular research : GMR | Year: 2016

The objective of this study was to identify hub genes and pathways associated with acute respiratory infection (ARI) in infants based on gene expression profiles. Differentially expressed genes (DEGs) between ARI and normal (controls) infants were identified based on linear modeling of the microarray data using Limma package. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/proteins and clusters were obtained by employing the molecular complex detection algorithm. Topological centrality was applied to characterize the biological importance of genes in the network. Functional enrichment analysis of the genes was performed based on the expression analysis systematic explore test. In total, 116 DEGs between ARI and controls were identified. Of the 61 nodes and 189 edges in the PPI network generated with the DEGs, three clusters were mined. Six hub genes namely RPL6, RPL3, EEF1B2, RPL15, EEF1A1, and RPS2, which were identified based on the topological centrality measures, were evaluated further. Functional enrichment analysis revealed that DEGs were significantly enriched in terms of Gene Ontology translational elongation, structural constituent of ribosome, and cytosol. The most significant term of pathway analysis was ribosome. In summary, this study suggests RPL6, RPL3, and RPL15 as hub genes and the ribosome pathway to be significantly associated with viral ARI in infants, which might also be used as potential markers for the viral etiology.


PubMed | The Third Hospital of Jinan
Type: Journal Article | Journal: World journal of gastroenterology | Year: 2016

To determine the association of p53, carcinoembryonic antigen (CEA) and CA19-9 protein expression with esophageal carcinogenesis.An iodine staining endoscopic screening program of esophageal lesions was carried out in the high-incidence area of Feicheng County, China. Seventy-seven patients with basal cell hyperplasia (BCH), 247 with low-grade dysplasia (LGD), 51 with high-grade dysplasia (HGD), 134 with invasive cancer, and 80 normal controls diagnosed by mucous membrane biopsy pathology were enrolled. Immunohistochemical detection of p53, CEA and CA19-9 proteins was performed. In the ROC curve analysis, the expression of a single biomarker and the expression of a combination of biomarkers were used to predict the risk of these four esophageal lesions.The positive rates of p53 protein expression in invasive cancer, HGD, LGD, BCH and the normal control groups were 53.0%, 52.9%, 35.6%, 27.3% and 20.0%, respectively; the positive rates of CA19-9 protein expression were 44.0%, 33.3%, 16.5%, 9.2% and 6.2%, respectively; the positive rates of CEA protein expression were 74.6%, 60.8%, 23.3%, 23.7% and 16.2%, respectively. The positive rates of the combined expression of the three biomarkers were 84.3%, 76.5%, 47.6%, 42.9% and 27.5%, respectively. In the receiver operating characteristic curves of the combination of the three biomarkers, the specificity was 88.8% for the normal controls, and the sensitivity was 58.2% for invasive cancer, 25.5% for HGD, 11.2% for LGD, and 6.5% for BCH.p53, CEA and CA19-9 protein expression was correlated with esophageal carcinogenesis, and testing for the combination of these biomarkers is useful for identifying high-risk patients with precancerous lesions.


PubMed | The Third Hospital of Jinan and Shandong University
Type: Journal Article | Journal: Molecular medicine reports | Year: 2016

The aim of the present study was to identify the genetic defect responsible for familial coronary artery disease/myocardial infarction (CAD/MI), which exhibited an autosomal dominant pattern of inheritance, in an extended Chinese Han pedigree containing 34 members. Using exome and Sanger sequencing, a novel 6base pair (bp) CAGCCG deletion in exon11 of the myocyte enhancer factor 2A (MEF2A) gene was identified, which cosegregated with CAD/MI cases in this family. This 6bp deletion was not detected in 311sporadic cases of premature CAD/MI or in 323unrelated healthy controls. Determination of a genetic risk profile has a key role in understanding the pathogenesis of CAD and MI. Among the reported riskconferring genes and their variants, mutations in MEF2A have been reported to segregate with CAD/MI in Caucasian families. Causative missense mutations have also been detected in sporadic CAD/MI cases. However, this suggested genetic linkage is controversial, since it could not be confirmed by ensuing studies. The discovery of a novel MEF2A mutation in a Chinese family with premature CAD/MI suggests that MEF2A may have a significant role in the pathogenesis of premature CAD/MI. To better understand this association, further invitro and invivo studies are required.


PubMed | The Third Hospital of Jinan
Type: Journal Article | Journal: Journal of B.U.ON. : official journal of the Balkan Union of Oncology | Year: 2016

To evaluate the cytotoxic and apoptotic effects of bishydroxycoumarin (BHC) against human glioma cells and to study their mode of action.Three cells were used in the experiments. MTT and LDH assays were used to assess the cytotoxic effects of BHC while an in vitro wound healing assay was used to study the effect of BHC on cell migration. Fluorescence microscopy and annexin V-FITC assay were used to study the cellular morphology and apoptotic effects while flow cytometry in combination with propidium iodide (PI) were used to study cell cycle arrest induced by BHC.BHC induced substantial and dose-dependent cytotoxic effects against all three cell lines with U87MG cell line being most susceptible. BHC also inhibited cell migration and induced characteristic morphological changes including chromatin condensation, nuclear shrinkage which increased with increasing dose of BHC. The apoptotic cell population (both early and late apoptotic cells) increased with increasing dose of BHC which also induced substantial G0/G1 cell cycle growth arrest in U87MG cells.This study provides help to elucidate the translational potential of the in vitro results to be used for further in vivo studies on human glioma using animal or human subjects. The mechanistic pathway studied in this report could be helpful in explaining the mode of action of these classes of natural products.


PubMed | The Third Hospital of Jinan and Shandong University
Type: Journal Article | Journal: Genetics and molecular research : GMR | Year: 2016

Despite recent advances in osteosarcoma diagnosis and therapy, much remains unclear about the molecular mechanisms involved in the disorder, and the discovery of novel drug-targeted genes is essential. We explored the potential molecular mechanisms and target genes involved in the development and progression of osteosarcoma. First, we identified the differentially expressed genes in osteosarcoma patients and matching normal controls. We then constructed a differential expression network based on differential and non-differential interactions. Pathway-enrichment analysis was performed based on the nodes contained in the main differential expression network. Centrality analysis was used to select hub genes that may play vital roles in the progression of human osteosarcoma. Our research revealed a total of 176 differentially expressed genes including 82 upregulated and 94 downregulated genes. A differential expression network was constructed that included 992 gene pairs (1043 nodes). Pathway-enrichment analysis indicated that the nodes in the differential expression network were mainly enriched in several pathways such as those involved in cancer, cell cycle, ubiquitin-mediated proteolysis, DNA replication, ribosomes, T-cell receptor signaling, spliceosomes, neurotrophin signaling, oxidative phosphorylation, and tight junctions. Six hub genes (APP, UBC, CAND1, RPA, YWHAG, and NEDD8) were discovered; of these, two genes (UBC and RPA) were also found to be disease genes. Our study predicted that UBC and RPA had potential as target genes for the diagnosis and treatment of osteosarcoma.

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