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Li Y.,Sun Yat Sen University | Li R.-Q.,Sun Yat Sen University | Ou S.-B.,Sun Yat Sen University | Zhang N.-F.,Sun Yat Sen University | And 4 more authors.
Reproductive Biology and Endocrinology | Year: 2014

Background: Oocyte secreted factors (OSFs), including growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), play an important role in the process of follicular development and oocyte maturation. Since OSFs are expressed in oocytes and cumulus granulosa cells, the aim of the present study was to explore whether the expression levels of GDF9 and BMP15 mRNAs in cumulus granulosa cells can be used as molecular markers for predicting oocyte developmental potential.Methods: Cumulus cells of 2426 cumulus-oocyte complexes were collected from 196 female patients who underwent intracytoplasmic sperm injection (ICSI) and were used for mRNA detection on the egg retrieval day. Pearson correlation analysis was used to analyze the correlation between OSF expression and general physiological parameters. Partial correlation analysis was used to analyze the correlation between OSF expression and oocyte developmental potential. Covariance analysis was used to compare OSF expression among different groups. Receiver operating characteristic curves were used to examine the diagnostic value of GDF9 and BMP15 mRNA for predicting pregnancy.Results: The expression levels of GDF9 and BMP15 mRNAs were significantly associated with age, body mass index (BMI), oocyte maturation, normal fertilization, and cleavage rate (P < 0.05). The expression levels of GDF9 and BMP15 mRNAs in the group with high-quality embryos were significantly higher than those in the group without high-quality embryos (P < 0.05). The expression levels of GDF9 and BMP15 mRNAs in the pregnancy group were significantly higher than those in the nonpregnancy group (P < 0.05). The cut-off value of GDF9 mRNA for predicting pregnancy was 4.82, with a sensitivity of 82% and a specificity of 64%. The cut-off value of BMP15 mRNA for predicting pregnancy was 2.60, with a sensitivity of 78% and a specificity of 52%.Conclusions: The expression levels of GDF9 and BMP15 mRNAs were closely associated with oocyte maturation, fertilization, embryo quality, and pregnancy outcome; therefore, GDF9 and BMP15 mRNAs in cumulus granulosa cells may be considered as new molecular markers for predicting oocyte developmental potential. © 2014 Li et al.; licensee BioMed Central Ltd.


Zhang L.,First Affiliated Hospital of Gannan Medical College | Zhang L.,Nanchang University | Fu F.,Nanchang University
Chinese Journal of Cancer Biotherapy | Year: 2013

Objective: To study the expression and gene mutation of epidermal growth factor receptor (EGFR) in endometrial carcinoma tissues. Methods: 0ne hundred and four paraffin-embedded endometrial tissues were obtained from Tumor Hospital of Jiangxi Province and the Second Affiliated Hospital of Nanchang University from January 2007 to April 2011, including 56 endometrial carcinoma tissues, 18 endometrial atypical hyperplasia tissues, and 30 normal endometrial tissues. Immunohistochemistry was used to detect the expression of EGFR protein in the above tissues. Exon 19 and exon 21 of EFPR gene in endometrial carcinoma or normal endometrial tissues ere amplified by P assay, and the mutations were detected by sequencing. Results: The positive expression rate of EGFR in the endometrial carcinoma tissues was higher than that in the normal endometrial tissues (73. 2% [41/56] vs 30. 0% [9/30], P < 0.01) and that in atypical hyperplasia tissues (73. 2% [41/56] vs 44. 4% [8/18], P < 0.05). Further analysis indicated that, the positive expression rate of EGFR in the G3 endometrial carcinoma tissues was significantly higher than that in G1 (81.8% [9/11] vs 66.7% [12/18], P < 0.01) and G2 tissues (81.8% [9/11] vs 74.1% [20/27], P < 0.05), and the positive expression rate of EGFR in the > 1/2 myometrial invasion group was higher than that in the ≤ 1/2 myometrial invasion group (86.8% [33/38] vs 44.4% [8/18], P < 0.01). However, the expression of EGFR had no correlation with the FIGO stage and the lymph node metastasis of endometrial carcinoma. One endometrial carcinoma case showed the mutation of exon 19 (G2281A) in EGFR gene, whereas, no mutation was found in exon 21. Conclusion: The positive expression rate of F in endometrial carcinoma is correlated with the histological grade and the infiltration depth of muscular layer, and some endometrial carcinoma tissues show the mutation of exon 19 (G2281A) in EGFR gene.


Weng Z.,Huazhong University of Science and Technology | Weng Z.,Nanchang University | Zhou X.,Hubei Zhongshan Hospital | Liu X.,Nanchang University | And 3 more authors.
Journal of Craniofacial Surgery | Year: 2013

Trigeminal neuralgia is the worst pain that human beings have ever experienced. Few researches have illustrated perioperative pain in patients with trigeminal neuralgia undergoing radiofrequency thermocoagulation (RFT) of the gasserian ganglion under local anesthesia. Because there are some undeniable drawbacks of using intravenous short-term anesthesia during the intervention repeatedly, some physicians keep patients awake throughout the puncture procedure, using local anesthesia. The purpose of this investigation was to examine perioperative pain in patients with trigeminal neuralgia undergoing RFT of the gasserian ganglion. Participants were 104 patients with classic trigeminal neuralgia. Worst pain intensity, mean pain intensity, quality of sleep, and analgesia satisfaction were evaluated for 24 hours before admission, 24 hours before operation, and 24 hours after operation. Intraoperative worst pain intensity was determined. Preoperative pain was serious, and preoperative sleep quality significantly and positively correlated with preoperative mean pain (r = 0.52; P = 0.00) and worst pain (r = 0.49; P = 0.00). Few patients (1.9%) responded to preoperative treatment, and the preoperative treatment obtained low analgesia satisfaction scores (3.9 [1.3]). Most patients experienced severe pain during cannulation under local anesthesia. No patients complained of pain during radiofrequency lesioning. The RFT of the gasserian ganglion alleviated pain obviously. Most patients (94.2%) responded to the operation, and the operation got high analgesia satisfaction scores (8.9 [0.7]). The results demonstrate that preoperative pain in patients with trigeminal neuralgia undergoing RFT of the gasserian ganglion is prevalent and undertreated and that intraoperative pain is severe under local anesthesia during cannulation. © 2013 by Mutaz B. Habal, MD.


Li J.-G.,Jiangxi Cancer Hospital | Yuan X.,Jiangxi Cancer Hospital | Zhang L.-L.,Jiangxi Maternity and Child Health Care Hospital | Tang Y.-Q.,Jiangxi Cancer Hospital | And 7 more authors.
Cancer | Year: 2013

Background This study sought to compare the clinical outcomes of upper versus whole-neck prophylactic irradiation in the treatment of patients with node-negative nasopharyngeal carcinoma (NPC). Methods Between November 2005 and June 2012, 301 patients with node-negative NPC were randomly assigned to receive primary plus prophylactic upper neck irradiation (UNI, 153 patients) or primary plus whole-neck irradiation (WNI, 148 patients). Patients in both groups received irradiation to the primary tumor and the upper neck nodal regions, and patients in the WNI group also received irradiation to the lower neck. The main endpoint of the study was to compare the lower neck control rate between the 2 groups. Results With a median follow-up period of 39 months (range, 6-84 months), no patient in either group had a cervical node relapse. The overall survival at 3 years was 89.5% (95% confidence interval [CI] = 84.1%-95.0%) in the UNI group and 87.4% (95% CI = 81.4%-93.5%) in the WNI group (hazard ratio [HR] = 0.866, 95% CI = 0.41-1.82; P =.70). The 3-year relapse-free survival rate was 89.8% and 89.3% (95% CI = 84.2%-95.3% and 83.7%-94.8%, HR = 0.914, 95% CI = 0.42-2.00; P =.82), and the 3-year metastasis-free survival rate was 91.7% and 90.9% (95% CI = 87.0%-96.5% and 85.7%-96.1%) for the UNI and WNI groups, respectively (HR = 1.007, 95% CI = 0.44-2.32; P =.99). Conclusions Prophylactic upper neck irradiation is sufficient for patients with node-negative NPC. © 2013 American Cancer Society.


Pan J.-P.,Huazhong University of Science and Technology | Zhang H.-Q.,First Affiliated Hospital of Gannan Medical College | Wei-Wang,Huazhong University of Science and Technology | Guo Y.-F.,Huazhong University of Science and Technology | And 3 more authors.
Brain Research | Year: 2011

ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) enhances cognitive functions; however, the underlying molecular mechanism remains unclear. Compelling evidence suggests that the endocannabinoid/endovanilloid systems play a pivotal role in regulating cognitive function. Thus, to correlate the effect of DHA on cognitive performance with the expression of endocannabinoid and endovanilloid receptors, we supplemented the diet of rats with DHA and performed in vitro experiments that focused on the endocannabinoid/endovanilloid receptors. We found that in vivo supplementation with an appropriate dose of DHA (150 or 300 mg/kg/d) significantly improved learning and memory but that a higher intake (600 mg/kg/d) increased the risk of memory impairment. In addition, we found that some subtypes of endocannabinoid/endovanilloid receptors (cannabinoid [CB] and transient receptor potential vanilloid [TRPV] receptors) were regulated in vitro by different concentrations of DHA in primary hippocampal neuron culture medium. Real-time polymerase chain reaction and western blot analysis showed that expression of both CB1 and TRPV1 was upregulated in a dose-dependent manner and reached a maximum level at 30 μmol/L (CB1) and 60 μmol/L (TRPV1) DHA. However, TRPV2 expression was downregulated in a dose-dependent fashion, and the peak of TRPV2 suppression was observed at 60 μmol/L. The dose-dependent effects of DHA on the expression of these receptors were well correlated with DHA's effect on spatial memory. Meanwhile, CB2, TRPV3, and TRPV4 expressions were not altered at diverse concentrations of DHA. We concluded that some subtypes of endocannabinoid/endovanilloid receptors might be involved in enhanced spatial memory induced by DHA supplementation. © 2011 Elsevier B.V. All rights reserved.


Wan D.,Soochow University of China | He S.,Soochow University of China | Xie B.,First Affiliated Hospital of Gannan Medical College | Xu G.,Jiangxi Cancer Hospital | And 6 more authors.
Medical Oncology | Year: 2013

Aberrant miR-199a-3p expression has been reported in several cancers. However, the clinical significance of miR-199a-3p in human colorectal cancer has not been addressed. In this study, we detected miR-199a-3p expression in 92 colorectal cancer cases to evaluate its clinicopathologic characteristics in colorectal cancer. We showed that miR-199a-3p expression was significantly upregulated in cancer tissues than NATs. Clinicopathologic analysis revealed that high miR-199a-3p expression contributed to more advanced lymphatic invasion, lymph node metastasis, liver metastases and late TNM stage in colorectal cancer. Kaplan-Meier analysis showed that high expression of miR-199a-3p could lead to a significantly shorter overall survival rate. Cox's proportional hazards model also indicated that the high expression of miR-199a-3p could serve as an independent and significant prognostic factor for survival. We transfected miR-199a-3p inhibitor into SW480 cells and observed that miR-199a-3p inhibitor could markedly inhibit the cell proliferation. Flow cytometry analysis also found that miR-199a-3p inhibitor could cause G0/G1 arrest, decreased percentage of S and G2/M phase and induce more cell apoptosis in SW480 cells. These results suggested that miR-199a-3p may serve as an efficient biomarker for diagnosis and novel prognostic indicator in colorectal cancer. © 2013 Springer Science+Business Media New York.


Liu Y.,University of Pittsburgh | Liu Y.,First Affiliated Hospital of Gannan Medical College | Yan W.,University of Pittsburgh | Yan W.,Huazhong University of Science and Technology | And 7 more authors.
Journal of Hepatology | Year: 2015

Background & Aims The mechanisms of hypoxia-induced tumor growth remain unclear. Hypoxia induces intracellular translocation and release of a variety of damage associated molecular patterns (DAMPs) such as nuclear HMGB1 and mitochondrial DNA (mtDNA). In inflammation, Toll-like receptor (TLR)-9 activation by DNA-containing immune complexes has been shown to be mediated by HMGB1. We thus hypothesize that HMGB1 binds mtDNA in the cytoplasm of hypoxic tumor cells and promotes tumor growth through activating TLR9 signaling pathways. Methods C57BL6 mice were injected with Hepa1-6 cancer cells. TLR9 and HMGB1 were inhibited using shRNA or direct antagonists. HuH7 and Hepa1-6 cancer cells were investigated in vitro to determine how the interaction of HMGB1 and mtDNA activates TLR9 signaling pathways. Results During hypoxia, HMGB1 translocates from the nucleus to the cytosol and binds to mtDNA released from damaged mitochondria. This complex subsequently activates TLR9 signaling pathways to promote tumor cell proliferation. Loss of HMGB1 or mtDNA leads to a defect in TLR9 signaling pathways in response to hypoxia, resulting in decreased tumor cell proliferation. Also, the addition of HMGB1 and mtDNA leads to the activation of TLR9 and subsequent tumor cell proliferation. Moreover, TLR9 is overexpressed in both hypoxic tumor cells in vitro and in human hepatocellular cancer (HCC) specimens; and, injection in mice to knockdown either HMGB1 or TLR9 from HCC cells suppressed tumor growth in vivo. Conclusions Our data reveals a novel mechanism by which the interactions of HMGB1 and mtDNA activate TLR9 signaling during hypoxia to induce tumor growth. © 2015 European Association for the Study of the Liver.


Chen M.,University of Pittsburgh | Chen M.,Huazhong University of Science and Technology | Liu Y.,University of Pittsburgh | Liu Y.,First Affiliated Hospital of Gannan Medical College | And 8 more authors.
Cancer Research | Year: 2015

Liver inflammation plays a critical role in hepatocellular carcinoma (HCC) etiology. Damage-associated molecular patterns (DAMP), such as high-mobility group box 1 (HMGB1), and dysregulated miRNAs involved in inflammatory disease states, such as miR-21, may participate in the link between inflammation and cancer. We sought to determine the role of HMGB1 signaling in HCC tumor progression. We first document the concordant expression increase of HMGB1 and miR-21 in HCC cell lines and primary HCC tumor samples and subsequently show that HMGB1 stimulation results in overexpression of miR-21. These changes were found to be dependent on the IL6/STAT3 signaling axis. Invasion and migration of HCC cells in vitro were inhibited by both STAT3 and miR-21 antagonists, suggesting a role for this pathway in HCC tumor progression. We verified that HMGB1-induced expression of miR-21 in HCC provides a posttranscriptional repression of the matrix metalloproteinase (MMP) inhibitors RECK and TIMP3, which are known to impact HCC progression and metastases. Finally, we found that inhibition of miR-21 in murine HMGB1-overexpressing HCC xenografts led to reduced tumor MMP activity through released repression of the miR-21 targets RECK and TIMP3, which ultimately impeded tumor progression. The prototypical DAMP, HMGB1, is released during liver inflammation and provides a favorable environment for HCC growth. HMGB1 signaling increases miR-21 expression to mediate the enhanced activity of MMPs through RECK and TIMP3. These findings provide a novel mechanism for HMGB1- mediated HCC progression through the IL6/Stat3-miR-21 axis. © 2015 American Association for Cancer Research.


Deng W.,First Affiliated Hospital of Gannan Medical College | Wei C.-P.,First Affiliated Hospital of Gannan Medical College | Liu X.-Z.,First Affiliated Hospital of Gannan Medical College
Chinese Journal of Tissue Engineering Research | Year: 2013

Background: Although the artificial hydroxyapatite is similar as the structure of inorganic composition of human sclerous tissues, its biological property has determinate difference compared to natural tooth and bone tissue. Objective: To analyze the components and crystal characteristics of the synthetic material extracted from dental enamel. Methods: The dental enamel power of clinical orthodontic teeth was collected. The power was treated with acid base, modified by tetracycline and then to form the tetracycline-calcium-phosphorus colloid. There were four groups including Group 1 (the dental enamel power), Group 2 (the dental enamel power+tetracycline), Group 3 (the dental enamel power+tetracycline+chitin) and Group 4 (the dental enamel power+tetracycline+chitin+liquid phase). All of them were detected by X-ray diffraction, infrared spectrum and field emission scan electron microscope. Liquid phase was prepared by 0.125 mol/L NaH2PO4 and 0.125 mol/L Na2HPO4 dissolved in distilled water. Results and Conclusion: The basic phase composition of apatite changed from the single component to multiple phases after the dental enamel was modified by tetracycline. The crystallinity decreased after the dental enamel extraction was modified by tetracycline; however, the adamantine crystallinity obviously increased after the chitin was added. These findings suggest that the main component of the dental enamel extraction is hydroxyapatite; the crystallographic characteristics of apatite, such as the phase, crystallinity and microconstituenis content has obvious modification after the dental enamel is modified by tetracycline; the crystallinity of apatite modified by tetracycline could increase by adding the chitin.


Zhang Z.B.,First Hospital of Changsha | Li Z.G.,First Affiliated Hospital of Gannan Medical College
Neurochemical Research | Year: 2012

Cathepsin B, one of major lysosomal cathepsins, and JNK, a downstream component of Rho kinase (ROCK), are two families of proteases, which play an important role in ischemic cell apoptosis. However, the interrelationship between Cathepsin B and JNK in apotosis has not been examined. In the present study, rats were decapitated at 0, 2, 6, 24, 48 h of reperfusion after 2 h of middle cerebral artery occlusion (MCAO); TUNEL-positive cells appeared in the ipsilateral preoptic region during reperfusion after 2-h MCAO, and gradually increased to a peak of 24 h after reperfusion; Phospho-JNK (p-JNK) immunoreactivity, occurring after Cathepsin B expression, was gradually increased and peaked altogether with Cathepsin B at 6-h reperfusion; Fasudil (5 mg/kg, intraperitoneally), an inhibitor of ROCK, decreased the level of p-JNK and apoptotic neurons, and had no effect on cathepsin B; Immunofluorescent double labeling showed that the colocalization of cathepsin B with p-JNK appeared in the preoptic region at 2, 6, 24, 48 h of reperfusion. These findings indicate that a signal transduction pathway by ischemia-reperfusion is most likely to exist: lysosomal cathepsin B-Rho/Rho kinase pathway-JNK signaling pathway-mitochondrial-dependent intrinsic pathway. © Springer Science+Business Media, LLC 2012.

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