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Zhang H.,PLA Fourth Military Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2016

OBJECTIVE: To investigate the survival benefit of cytoreductive surgery in gastric cancer patients with peritoneal metastasis.METHODS: Clinicopathological data of 151 advanced gastric adenocarcinoma patients with extensive peritoneal metastasis who were identified by surgical exploration between May 2008 and April 2015 in Xijing Hospital of Digestive Diseases were analyzed retrospectively. Of all the patients, 32 cases were treated by cytoreductive surgery with local radical tumor resection and regional lymph node cleaning, combined with fluorouracil-based adjuvant chemotherapy after surgery (cytoreductive surgery combined with chemotherapy group); 39 caseswere only treated by cytoreductive surgery group(cytoreductive surgery group);23 caseswere treated bysurgical exploration combined with fluorouracil-based adjuvant chemotherapy after surgery(surgical exploration combined with chemotherapy group) and 57 cases were only treated bysurgical exploration (surgical exploration group). The overall survival of four groups were analyzed and compared.RESULTS: Among the 151 patients, 148 (98.0%) patients were followed up. The median follow up time was 7.2 months (range 1.4-61.2). The median survival of cytoreductive surgery combined with chemotherapy group, cytoreductive surgery group, surgical exploration combined with chemotherapy group and surgical exploration group was 11.9(95% CI: 8.8-15.1) months, 7.1(95% CI: 3.2-11.1) months, 8.2(95% CI:4.6-11.8) and 5.4(95% CI:4.4-6.4) months, respectively(P < 0.01).CONCLUSIONS: Cytoreductive surgery can prolong the survival of gastric adenocarcinoma patients with extensive peritoneal metastasis. Cytoreductive surgery combined with chemotherapy may provide more benefit for patients, and can be used as a choice of treatment in these patients.


Zhu H.,State University of New York at Stony Brook | Fan Y.,State University of New York at Stony Brook | Lu H.,PLA Fourth Military Medical University | Liang Z.,State University of New York at Stony Brook
Physics in Medicine and Biology | Year: 2010

Reducing the number of false positives (FPs) as much as possible is a challenging task for computer-aided detection (CAD) of colonic polyps. As part of a typical CAD pipeline, an accurate and robust process for segmenting initial polyp candidates (IPCs) will significantly benefit the successive FP reduction procedures, such as feature-based classification of false and true positives (TPs). In this study, we introduce an improved scheme for segmenting IPCs. It consists of two main components. One is geodesic distance-based merging, which merges suspicious patches (SPs) for IPCs. Based on the merged SPs, another component, called convex dilation, grows each SP beyond the inner surface of the colon wall to form a volume of interest (VOI) for that IPC, so that the inner border of the VOI beyond the colon inner surface could be segmented as convex, as expected. The IPC segmentation strategy was evaluated using a database of 50 patient studies, which include 100 scans at supine and prone positions with 84 polyps and masses sized from 6 to 35 mm. The presented IPC segmentation strategy (or VOI extraction method) demonstrated improvements, in terms of having no undesirably merged true polyp and providing more helpful mean and variance of the image intensities rooted from the extracted VOI for classification of the TPs and FPs, over two other VOI extraction methods (i.e. the conventional method of Nappi and Yoshida (2003 Med. Phys. 30 1592-601) and our previous method (Zhu et al 2009 Cancer Manag. Res. 1 1-13). At a by-polyp sensitivity of 0.90, these three methods generated the FP rate (number of FPs per scan) of 4.78 (new method), 6.37 (Nappi) and 7.01 (Zhu) respectively. © 2010 Institute of Physics and Engineering in Medicine.


Traditional Chinese medicinal herbs Cortex Moutan and Radix Salviae Milthiorrhizaeare are prescribed together for their putative cardioprotective effects in clinical practice. However, the rationale of the combined use remains unclear. The present study was designed to investigate the cardioprotective effects of paeonol and danshensu (representative active ingredient of Cortex Moutan and Radix Salviae Milthiorrhizae, respectively) on isoproterenol-induced myocardial infarction in rats and its underlying mechanisms. Paeonol (80 mg kg(-1)) and danshensu (160 mg kg(-1)) were administered orally to Sprague Dawley rats in individual or in combination for 21 days. At the end of this period, rats were administered isoproterenol (85 mg kg(-1)) subcutaneously to induce myocardial injury. After induction, rats were anaesthetized with pentobarbital sodium (35 mg kg(-1)) to record electrocardiogram, then sacrificed and biochemical assays of the heart tissues were performed. Induction of rats with isoproterenol resulted in a marked (P<0.001) elevation in ST-segment, infarct size, level of serum marker enzymes (CK-MB, LDH, AST and ALT), cTnI, TBARS, protein expression of Bax and Caspase-3 and a significant decrease in the activities of endogenous antioxidants (SOD, CAT, GPx, GR, and GST) and protein expression of Bcl-2. Pretreatment with paeonol and danshensu combination showed a significant (P<0.001) decrease in ST-segment elevation, infarct size, cTnI, TBARS, protein expression of Bax and Caspase-3 and a significant increase in the activities of endogenous antioxidants and protein expression of Bcl-2 and Nrf2 when compared with individual treated groups. This study demonstrates the cardioprotective effect of paeonol and danshensu combination on isoproterenol-induced myocardial infarction in rats. The mechanism might be associated with the enhancement of antioxidant defense system through activating of Nrf2 signaling and anti-apoptosis through regulating Bax, Bcl-2 and Caspase-3. It could provide experimental evidence to support the rationality of combinatorial use of traditional Chinese medicine in clinical practice.


Zhang H.,PLA Fourth Military Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2016

OBJECTIVE: To compare the survival rate of proximal gastrectomy and total gastrectomy in the treatment of esophagogastric junction (EGJ) adenocarcinoma (Siewert II( types), and to provide reference for clinical choice.METHODS: A total of 533 patients with Siewet II( type EGJ adenocarcinoma were screened. All the patients underwent radical operations and were pathologically diagnosed as Siewet II( type EGJ adenocarcinoma in Xijing Hospital of Digestive Diseases from May 2008 to March 2014. These patients all had complete followed-up data. Finally, 234 patients were enrolled into the retrospective study, and divided into proximal gastrectomy group(117 patients) and total gastrectomy group (117 patients) based on the matching of age, sex, tumor size, TNM staging, and differentiation. The survival rate was compared between the two groups.RESULTS: In proximal gastrectomy and total gastrectomy group, the overall 3-year survival rate was 65.6% and 62.6% respectively, and the overall 5-year survival rate was 53.8% and 44.5% respectively. No significant difference was found between the two groups (P=0.768). In subgroup analyses of 3-year survival rate between proximal gastrectomy group and total gastrectomy group, the results were as follows: 72.8% and 80.4% respectively (P=0.423) for tumor diameter ≤4 cm, 57.9% and 46.5% (P=0.239) for tumor diameter >4 cm, 83.3% and 83.3% (P=0.998) for high differentiated EGJ adenocarcinoma, 68.2% and 53.3% (P=0.270) for moderate differentiated EGJ adenocarcinoma, 56.1% and 69.6% (P=0.280) for poorly differentiated EGJ adenocarcinoma, 64.8% and 56.0% (P=0.451) for mucinous EGJ adenocarcinoma, 80.0% and 76.9% (P=0.912) for T1-2 stage EGJ adenocarcinoma, 64.3% and 60.4% (P=0.610) for T3 stage, 50.0% and 62.5% (P=0.953) for T4a stage, 92.3% and 100% (P=0.380) for stage I( EGJ adenocarcinoma, 79.6% and 66.3%(P=0.172) for stage II(, 42.6% and 49.5% (P=0.626) for stage I I(. All above differences between the two groups were not significant(all P>0.05).CONCLUSION: Proximal gastrectomy and total gastrectomy are comparable in terms of 3-year and 5-year survival rates.


Zhao Q.,PLA Fourth Military Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2016

Enhanced recovery after surgery (ERAS), a new model of perioperative management developed in recent years, can shorten hospital stay, reduce medical cost and postoperative discomfort. However, some of these measures under the strategy are negation of the traditional recommendation and many surgeons are concerned about the medical tangle by the complications coming with the ERAS strategy. In this paper, ERAS strategy is evaluated from an ethical standpoint and the assessment factors of medical behavior are introduced based on medical virtues and medical ethnics. It is also analyzed that how to deal with the conflicts between the textbooks and the ERAS strategy, and elaborated that the medical ethics should be observed if the ERAS strategy is implemented. The scientific principles must be followed, the rights and interests of the patients need to be protected, and the informed consent should be guaranteed.


Vascular invasion and admixture of the nude mouse cells with seeded cells make it difficult to reapply the regenerated tissues to the restoration of host tissue defects. Therefore, a device that is capable of allowing for autologous or allogenic tissue growth while preventing host tissue invasion will be a valuable tool for in vivo tissue engineering. We have previously fabricated a novel silicon-perforated chamber. The aim of this study was to evaluate whether this chamber, after being implanted subcutaneously in experimental animals, would hinder host tissue ingrowth while providing an environment inside its cavity for in vivo growth of either autologous or allogenic implant cells. We found that the chamber did not induce severe foreign body reaction, and the chambers with perforated pores of 1-3 mm in diameter effectively inhibited the host granulation tissue or vascular invasion for as long as 3 months. In addition, the exudates rich in vascular endothelial growth factor, basic fibroblast growth factor, transforming growth factor-β, insulin-like growth factor-1, and platelet-derived growth factor-BB were steadily generated and collected in the chambers. In vitro cell culture studies revealed that the exudates were able to support the viability and proliferation of rabbit chondrocytes, rat mesenchymal stem cells, and human fibroblasts. The results indicate that this novel chamber could potentially provide an environment favorable for in vivo tissue engineering while effectively preventing host tissue or vascular invasion.


Wang J.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2012

To isolate and identify single chain Fv (scFv) antibodies against breast cancer from a constructed human phage display library. Recombinant phages specific for breast cancer cells were enriched after four-round screening with MCF-7 cells. We selected the antigen-positive ones from the enriched clones by phage ELISA. The positive clones were used to infect E.coli HB2151 to express soluble scFv antibody. The antigen binding activity of the soluble antibodies was detected by Western blotting. The specific antibodies against MCF-7 cells were enriched after four rounds of affinity selection. SDS-PAGE and Western blotting showed a band at relative molecular mass 30 000 Da, which indicated soluble antibodies were present. ELISA analysis revealed that soluble antibodies had the affinity to a human breast cancer cell line MCF-7 but not to other cancer cell line, which demonstrated scFv could react specifically with breast cancer cells. We constructed a scFv phage library against human breast cancer with high capacity by phage display technology. The scfv was demonstrated successfully to be expressed in E.coli HB215 and have a specificity to breast cancer. Our findings may provide an alternative approach, and a basis for further studies on diagnosis and therapy of breast cancer.


Zhang J.,University of Houston | Zhang J.,PLA Fourth Military Medical University | Guo X.,University of Houston | Guo X.,Shihezi University | And 5 more authors.
Modern Pathology | Year: 2012

As a putative marker for cancer stem cells in human malignant tumors, including ovarian cancer, CD133 expression may define a tumor-initiating subpopulation of cells and is associated with the clinical outcome of patients. However, at this time its clinical significance in ovarian cancer remains uncertain. The aim of this study was to clarify the clinical role of CD133 expression in human ovarian cancer. Immunohistochemical staining of CD133 expression was performed in 400 ovarian carcinoma samples using tissue microarray. The associations among CD133 expression and clinical factors (diagnosis, tumor grade, cancer stage, and clinical response to chemotherapy), overall survival and disease-free survival time were analyzed. CD133 expression was found in 31% of ovarian carcinoma samples. Fisher's exact test and one-way analysis of variance suggested that CD133 expression was associated with high-grade serous carcinoma (P=0.035), late-stage disease (P<0.001), ascites level (P=0.010), and non-response to chemotherapy (P=0.023). CD133 expression was also associated with shorter overall survival time (P=0.007) and shorter disease-free survival time (P<0.001) by log-rank test. Moreover, CD133 expression was an independent predictor of shorter disease-free survival time in an unconditional logistic regression analysis with multiple covariates (P=0.024). Our results thus show that CD133 expression is a predictor of poor clinical outcome for patients with ovarian cancer, supporting the proposed link between CD133 and cancer stem cells. © 2012 USCAP, Inc. All rights reserved.


Wang C.H.,PLA Fourth Military Medical University
Zhonghua er ke za zhi. Chinese journal of pediatrics | Year: 2010

To investigate the effect of interstitial cells of Cajal (ICC) on contraction of intestinal tract smooth muscle induced by motilin receptor agonist. Two kinds of smooth muscle segments were isolated from the duodenum and colon of rabbit. Both kinds of smooth muscle were divided into two groups: group a (normal ICC group of duodenum); group c (impaired ICC group of duodenum); group b (normal ICC group of colon); group d (impaired ICC group of colon), each group contained 20 segments. The impairment of ICC was induced by selectively destroying ICC in the smooth muscle via treatment with methylene blue plus light. Then the frequency and amplitude of contraction of group a and c, group b and d was compared. Then motilin receptor agonist (ABT-229) was added into the Krebs solution, the frequency and amplitude of smooth muscle contraction before and after adding ABT-229 were recorded and compared. The electron microscopy demonstrated that ICC in methylene blue plus light group were destroyed; the smooth muscle cells and neuron scattered close to ICC were normal. In group a, the contraction frequency, (17.89 +/- 1.88) times/min, was significantly lower as compared with that measured after ABT-229 was added [(18.76 +/- 1.18) times/min (P > 0.05)]; the amplitude of group a was (343 +/- 28) mg, which was lower as compared with that after adding ABT-229 [(597 +/- 68) mg (P < 0.001)]; in group b, the frequency was (5.89 +/- 1.03) times/min, the amplitude was (724 +/- 85) mg, after ABT-229 was added, the construction frequency increased to (8.45 +/- 0.69) times/min (P < 0.001), and the amplitude was (897 +/- 89) mg (P < 0.05), which was not affected by pretreatment with TTX, however it could be weakened by nifedipine significantly. In group c and d, the rhythmic contraction almost disappeared: in group c the contraction frequency was (1.06 +/- 0.24) times/min, and the amplitude were (50 +/- 10) mg. In group d, the amplitude and frequency significantly decreased as compared with the normal group (P < 0.001), in group c, and d, no significant difference in amplitude and frequency was found between the values measured before and after adding ABT-229 (P > 0.05). After Ach (100 micromol/L) was added, both group c and d could generate contraction. ICC may play an important role in the rhythmic contraction of intestinal tract. The promoting effect of motilin receptor agonist on intestinal tract may be mediated by ICC. ICC deficiency may cause functional impairment of gastrointestinal tract motivation. The medication may become ineffective when the number of ICC is reduced to a certain extent or the network of ICC is incomplete.


Gao F.,PLA Fourth Military Medical University
Sheng li xue bao : [Acta physiologica Sinica] | Year: 2012

The aim of the present study was to evaluate the active and passive mechanical properties and wall collagen and elastin contents of mesenteric small arteries (MSAs) isolated from rats of 28-day simulated microgravity (SUS), countermeasure [S + D: SUS plus 1 h/d -G(x) to simulate intermittent artificial gravity (IAG)] and control (CON) groups. Three mechanical parameters were calculated: the overall stiffness (β), circumferential stress (σ(θ))-strain (ε(θ)) relationship and pressure-dependent incremental elastic modulus (E(inc,p)). Vessel wall collagen and elastin percentage were quantified by electron microscopy. The results demonstrate that the active mechanical behavior of MSAs differs noticeably among the three groups: the active stress-strain curve of SUS vessels is very close to the passive curve, whereas the active σ(θ)-ε(θ) curves of CON and S + D vessels are shifted leftward and display a parabolic shape, indicating that for MSAs isolated from S + D, but not those from SUS rats, the pressure-induced myogenic constriction can effectively stiffen the vessel wall as the CON vessels. The passive mechanical behavior of MSAs does not show significant differences among the three groups. However, the percentage of collagen is decreased in the wall of SUS and S + D compared with CON vessels in the following order: SUS < S + D < CON. Thus, the relationship between passive mechanical behavior and compositional changes may be complex and yet depends on factors other than the quantity of collagen and elastin. These findings have provided biomechanical data for the understanding of the mechanism of postflight orthostatic intolerance and its gravity-based countermeasure.


Li X.,PLA Fourth Military Medical University | Chen J.,Xian Jiaotong University
Journal of Convergence Information Technology | Year: 2012

To improve the accuracy and efficiency of pathological diagnosis, this paper analyzes and presents knowledge acquisition, notation and reasoning mechanism of pathologic diagnosis expert system. Methods and steps of knowledge acquisition are particularly analyzed. The existing knowledge notations and reasoning mechanism are studied on the base. The pathologic system has the characters of huge information and coupling, so this paper uses production rules to note knowledge and introduced reliability to deduce imprecisely and finally generates the diagnosis report and treatment scheme. The method is of highly feasibility and effectiveness.


Shen H.,Chinese PLA General Hospital | Tang G.,First Affiliated Hospital of the General Hospital of the Peoples Liberation Army | Zeng G.,PLA Fourth Military Medical University | Yang Y.,Chinese PLA General Hospital | And 4 more authors.
Carbohydrate Polymers | Year: 2013

In the present study, we purified a unique polysaccharide component (POP) from Portulaca oleracea and found that it had pronounced anti-tumor effects in vivo model. Tumor weight, immune organ index and T lymphocyte subsets were employed to detect the immunoregulatory and antitumor effects of POP after administration. Hematological and biochemical analyses were also investigated in order to evaluate the toxicological aspects related to POP treatment. POP could significantly inhibit the growth of transplantable sarcoma 180 and potentiate the animal's immune responses including an increase in the number of white blood cell (WBC) and CD4+ T-lymphocytes, as well as the ratio of CD4 +/CD8+. Furthermore the serum aspartate transanimase (AST), alanine transaminase (ALT), urea nitrogen (BUN), and creatinine levels in S180-bearing mice were significantly reversed by POP. Considering all these results, it is suggested that the anti-tumor effect elicited by POP could be associated with its immunostimulating properties. © 2012 Elsevier Ltd.


The present study was designed to test the hypothesis that a medium-term simulated microgravity can induce region-specific remodeling in large elastic arteries with their innermost smooth muscle (SM) layers being most profoundly affected. The second purpose was to examine whether these changes can be prevented by a simulated intermittent artificial gravity (IAG). The third purpose was to elucidate whether vascular local renin-angiotensin system (L-RAS) plays an important role in the regional vascular remodeling and its prevention by the gravity-based countermeasure. This study consisted of two interconnected series of in-vivo and ex-vivo experiments. In the in-vivo experiments, the tail-suspended, hindlimb unloaded rat model was used to simulate microgravity-induced cardiovascular deconditioning for 28 days (SUS group); and during the simulation period, another group was subjected to daily 1-hour dorso-ventral (-G(x)) gravitation provided by restoring to normal standing posture (S + D group). The activity of vascular L-RAS was evaluated by examining the gene and protein expression of angiotensinogen (Ao) and angiotensin II receptor type 1 (AT1R) in the arterial wall tissue. The results showed that SUS induced an increase in the media thickness of the common carotid artery due to hypertrophy of the four SM layers and a decrease in the total cross-sectional area of the nine SM layers of the abdominal aorta without significant change in its media thickness. And for both arteries, the most prominent changes were in the innermost SM layers. Immunohistochemistry and in situ hybridization revealed that SUS induced an up- and down-regulation of Ao and AT1R expression in the vessel wall of common carotid artery and abdominal aorta, respectively, which was further confirmed by Western blot analysis and real time PCR analysis. Daily 1-hour restoring to normal standing posture over 28 days fully prevented these remodeling and L-RAS changes in the large elastic arteries that might occur due to SUS alone. In the ex-vivo experiments, to elucidate the important role of transmural pressure in vascular regional remodeling and differential regulation of L-RAS activity, we established an organ culture system in which rat common carotid artery, held at in-vivo length, can be perfused and pressurized at varied flow and pressure for 7 days. In arteries perfused at a flow rate of 7.9 mL/min and pressurized at 150 mmHg, but not at 0 or 80 mmHg, for 3 days led to an augmentation of c-fibronectin (c-FN) expression, which was also more markedly expressed in the innermost SM layers, and an increase in Ang II production detected in the perfusion fluid. However, the enhanced c-FN expression and increased Ang II production that might occur due to a sustained high perfusion pressure alone were fully prevented by daily restoration to 0 or 80 mmHg for a short duration. These findings from in-vivo and ex-vivo experiments have provided evidence supporting our hypothesis that redistribution of transmural pressures might be the primary factor that initiates region-specific remodeling of arteries during microgravity and the mechanism of IAG is associated with an intermittent restoration of the transmural pressures to their normal distribution. And they also provide support to the hypothesis that L-RAS plays an important role in vascular adaptation to microgravity and its prevention by the IAG countermeasure.


Koga K.,University of Toronto | Koga K.,University of Science and Technology of China | Liu M.-G.,University of Toronto | Liu M.-G.,Shanghai JiaoTong University | And 10 more authors.
Journal of Neuroscience | Year: 2015

Fragile X syndrome is a common inherited form of mental impairment. Fragile X mental retardation protein (FMRP) plays important roles in the regulation of synaptic protein synthesis, and loss of FMRP leads to deficits in learning-related synaptic plasticity and behavioral disability. Previous studies mostly focus on postsynaptic long-term potentiation (LTP) in Fmr1 knock-out (KO) mice. Here,we investigate the role ofFMRPin presynapticLTP(pre-LTP) in the adultmouseanterior cingulate cortex (ACC). Low-frequency stimulation induced LTP in layer II/III pyramidal neurons under the voltage-clamp mode. Paired-pulse ratio, which is a parameter for presynaptic changes, was decreased after the low-frequency stimulation in Fmr1 wild-type (WT) mice. Cingulate pre-LTP was abolished in Fmr1 KO mice. We also used a 64-electrode array system for field EPSP recording and found that the combination of low-frequency stimulation paired with a GluK1-containing kainate receptor agonist induced NMDA receptor-independent and metabotropic glutamate receptordependent pre-LTP in theWTmice. This potentiation was blocked in Fmr1KOmice. Biochemical experiments showed that Fmr1KOmice displayed altered translocation of protein kinase A subunits in the ACC. Our results demonstrate that FMRP plays an important role in pre-LTP in the adult mouse ACC, and loss of this pre-LTP may explain some of the behavioral deficits in Fmr1 KO mice. © 2015 the authors.


Tachykinins such as SP (substance P) may be involved in the progression of gastric adenocarcinoma through binding to NK-1 receptor. However, the existence and relationship between SP and gastric cancer progression and differentiation remained unknown. We have studied the NK-1 receptor in human gastric cancer tissue and MKN45 cell line and found SP-containing nerve fibres in human gastric cancer and found that the amounts of SP-positive nerves were related to gastric cancer differentiation. SP could promote proliferation, adhesion, migration and invasion of MKN45 cells in vitro. In addition, the intracellular calcium level of MKN45 cells was elevated after SP stimulation, and administration of CRACs (calcium release-activated calcium channels) inhibitor SKF-96365 could partially abolish these effects induced by SP. These results demonstrated that NK-1 receptor and SP-containing nerves existed in human gastric cancer; SP positive nerves may play an important role in human gastric cancer progression, and calcium is critically significant among SP-induced biological effects.


Zhou X.,PLA Fourth Military Medical University | Liu J.,China University of Petroleum - East China
Physica E: Low-Dimensional Systems and Nanostructures | Year: 2013

The stability of short DNA ring is phenomenologically analyzed by discussing the second variation of its elastic free energy. Through expanding the perturbation functions as Fourier series, the DNA ring's stability condition is obtained in a general case. This result is also suitable for other structures which can be taken as one-dimensional (1D) curvature elastomers, such as ribbons and filaments. Stability analysis in a typical model provides some useful results which are consistent with the experimental observations in a wide parameter range. © 2012 Elsevier B.V. All rights reserved.


Fournier P.,German Cancer Research Center | Bian H.,PLA Fourth Military Medical University | Szeberenyi J.,University of Pecs | Schirrmacher V.,German Cancer Research Center
Methods in Molecular Biology | Year: 2012

Newcastle disease virus (NDV), a bird paramyxovirus, is an antitumor agent which has shown benefits to cancer patients. Its antineoplastic efficacy appears to be associated with three properties of the virus: 1. Selective replication in tumor cells. This feature can be studied at the RNA level, for example by RT-PCR, and at the protein level by immunochemistry. 2. Oncolytic properties (of some strains). The use of cultures of tumor cell lines represents a selective model to study direct viral oncolysis at the cellular level. The capacity of NDV to lyse tumor cells can be analyzed in vitro using cytotoxic assays based on the WST1 chemical reagent. The endoplasmic reticulum stress, which is induced by infection with the oncolytic NDV strain MTH-68/H and which plays an important role in the viral oncolytic effects, can be analyzed by Western blotting using specific monoclonal antibodies. Such stress appears as a key component of NDV cytotoxicity. 3. Immunostimulatory capacity. We describe an in vitro test called "Tumor Neutralisation Assay" which allows the analysis of bystander antitumor immune effects induced in human peripheral blood mononuclear cells by NDV. There are two variants, one for oncolytic NDV strains and the other one for nonlytic NDV strains. NDV may use several mechanisms to exert its tumor-killing action: direct cytotoxicity against cancer cells but also nonspecific as well as active-specific antitumor immune responses from the host organism. All the methods described here allow to evaluate the different oncolytic and immunostimulatory capacities of various strains of NDV. They are crucial to harness optimal antitumor activity by appropriate combinations of virus strains and application regimens. © 2012 Springer Science+Business Media, LLC.


Qu T.,Texas A&M University | Qu T.,PLA Fourth Military Medical University | Liu X.,Texas A&M University
Journal of Materials Chemistry B | Year: 2013

Tooth decay is one of the most common chronic disorders throughout the world. Regenerating decayed dentin/pulp structure requires the design of novel scaffolding materials that mimic the architecture of a natural dental extracellular matrix (ECM) and provide suitable environments for the attachment, proliferation, differentiation, and biomineralization of dental pulp stem cells (DPSCs). In this work, we developed an approach to prepare three-dimensional (3D) nano-fibrous gelatin/silica bioactive glass (NF-gelatin/SBG) hybrid scaffolds that mimic the nano-structured architecture and chemical composition of a natural dental ECM. This approach involved the combination of a thermally induced phase separation, sol-gel, and porogen leaching process, and synthesized hybrid scaffolds possessing natural ECM-like architecture, high porosity, well-defined pore size and interconnectivity, and improved mechanical strength. An in vitro cell culture study showed that human DPSCs had a significantly higher proliferation rate on NF-gelatin/SBG scaffolds compared to NF-gelatin scaffolds under the same conditions. Furthermore, the integration of SBG into the hybrid scaffold significantly promoted the differentiation and biomineralization of the human DPSCs. The alkaline phosphatase (ALP) activity and expressions of marker genes for odontogenic differentiation (Col I, ALP, OCN, DSPP and DMP-1) were all significantly higher in the NF-gelatin/SBG than in the NF-gelatin group. Those results were further confirmed by hematoxylin and eosin (H&E) and von Kossa staining, as evidenced by greater ECM secretion and mineral deposition in the hybrid scaffold. In summary, the biomimetic NF-gelatin/SBG hybrid scaffolds provide an excellent environment for the growth and differentiation of human DPSCs and are promising candidates for dentin/pulp tissue regeneration. © 2013 The Royal Society of Chemistry.


Wang H.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2013

To establish mouse models of membranous nephropathy (MN), and identify the physiological and histological characteristics of the models. BALB/c mice (6 weeks old) were randomly divided into 2 groups: an experimental group and a control group. Animals in the experimental group were immunized subcutaneously with 0.2 mg cationized bovine serum albumin (C-BSA) emulsified in an equal volume of complete Freunds adjuvant (CFA), and those in the control group were immunized with CFA and normal saline. Two weeks later, these mice in the experimental group received C-BSA via tail vein every other day, 3 times per week, and the control group received normal saline alone in the same way. The establishment of models was verified by serum, urine tests and pathological examinations (PASM staining, IgG immunofluorescence and transmission electron microscopy). Eight weeks later, 12 animals developed hypoalbuminemia, hypercholesterolemia and severe proteinuria in the experimental group. The PASM staining showed similar as the early stage of MN in morphology. Immunofluorescence staining for the experimental group exhibited granular deposition of IgG along the capillary wall, and ultrastructurally, the basement membrance showed fusion and effacement of podocyte foot processes and the deposits under a transmission electron microscope. We established successfully a murine model of MN induced by C-BSA.


Jia D.,PLA Fourth Military Medical University | Han B.,Xian Medical University | Yang S.,First Peoples Hospital of Xianyang | Zhao J.,Xian Medical University
Journal of Molecular Neuroscience | Year: 2014

In the present study, we aimed at evaluating the potential neuroprotective effect and the underlying mechanism of anemonin against cerebral ischemia and reperfusion (I/R) injury. Anemonin was administered to rats by the intraperitoneally (i.p.) route once daily for 7 days before middle cerebral artery occlusion (MCAO). Focal cerebral ischemia was induced by 90 min of MCAO followed by 24 h of reperfusion. After that, animals were sacrificed by decapitation, brain was removed, and various biochemical estimations, neurological status, and assessment of cerebral infarct size were carried out. MCAO followed by 24 h of reperfusion caused a significant increase in infarct size, neurological deficit score, malondialdehyde (MDA) content, reactive oxygen species (ROS) level, and DNA fragmentation, as well as a decrease in the activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and Na+, K+-ATPase in the brain. Furthermore, elevated Bax expression, increased caspase-3 cleavage, and decreased Bcl-2 expression were observed in nontreated rats in response to focal cerebral I/R injury. However, pretreatment with anemonin significantly reversed these levels of biochemical parameters, reduced cerebral infarct size, and improved the neurologic score in cerebral ischemic animals. Additionally, a wide distribution of anemonin in plasma and brain tissues and the brain-to-plasma partition coefficient (Ri) ratio of 0.7 at 90 min indicated that this compound could penetrate the blood-brain barrier (BBB). These results showed that pretreatment with anemonin provided a significant protection against cerebral I/R injury in rats by, at least in part, its antioxidant action and consequent inhibition of apoptosis. © 2014 Springer Science+Business Media.


Du T.,Tongji Medical College | Sun X.,PLA Fourth Military Medical University | Huo R.,Tongji Medical College | Yu X.,Tongji Medical College
International Journal of Obesity | Year: 2014

Background: The visceral adiposity index (VAI) and hypertriglyceridemic waist phenotype (the simultaneous presence of waist circumference (WC)≥90/80 cm for men/women and plasma triglyceride (TG) concentration≥1.7 mmol l -1 for both genders) have been identified as good indicators of visceral adiposity, which is an independent risk factor for diabetes. The Chinese population is characterized by a predominance of visceral fat accumulation despite having comparatively low weight. These two surrogate markers of visceral adiposity might effectively identify Chinese adults who are at risk of getting diabetes. We aimed to examine the association between VAI and risk of diabetes or between the hypertriglyceridemic waist phenotype and diabetes risk. Methods: We conducted a cross-sectional analysis of 7639 Chinese men and women aged ≥18 years using data from the China Health and Nutrition Survey 2009. Logistic regression was used to evaluate the associations. Results: For men, compared with participants in the lowest quartile of VAI scores, the multivariable-adjusted odds ratios (ORs) (with 95% confidence intervals) for diagnosed diabetes were 1.1 (0.7-1.7), 1.9 (1.3-2.8) and 3.6 (2.5-5.3) for those in the second, third, and top quartile of VAI scores, respectively. For women, the corresponding figures were 0.9 (0.5-1.4), 1.7 (1.1-2.6) and 2.8 (1.9-4.2), respectively. The multivariate-adjusted ORs (with 95% confidence intervals) for diabetes in men with the hypertriglyceridemic waist phenotype compared with men with both WC and TG measurements below the defined cut points were 3.7 (2.6-5.4). For women, the corresponding figure was 3.7 (2.4-5.5). For both men and women, the associations between the 4th quartile of VAI scores and risk of diabetes or between the hypertriglyceridemic waist phenotype and risk of diabetes were consistently seen in various subgroups. Conclusion: Among Chinese adults, high VAI scores and the hypertriglyceridemic waist phenotype are strongly associated with diabetes risk. © 2014 Macmillan Publishers Limited All rights reserved.


Shi X.,Shaanxi Normal University | Zhao Y.,PLA Fourth Military Medical University | Jiao Y.,Shaanxi Normal University | Shi T.,Shaanxi Normal University | Yang X.,Shaanxi Normal University
PLoS ONE | Year: 2013

Background:A greater reduction in cancer risk associated with mushroom diet rich in fungus polysaccharides is generally accepted. Meanwhile, edible Pleurotus abalonus as a member of Abalone mushroom family is a popular nutritional supplement that purportedly prevents cancer occurrence. However, these anecdotal claims are supported by limited studies describing tumor-inhibitory responses to the promising polysaccharides, and the molecular mechanisms underlying these properties have not yet been elucidated.Methodology/Principal Findings:We here fractionated the crude polysaccharide preparation from the fruiting bodies of P. abalonus into three fractions, namely PAP-1, PAP-2 and PAP-3, and tested these fractions for antiproliferative activity in human breast cancer MCF-7 cells. The largest PAP-3, an acidic polysaccharide fraction with a molecular mass of 3.68×105Da, was the most active in inhibiting MCF-7 cancer cells with an IC50 of 193 μg/mL. The changes in cell normal morphology were observed by DAPI staining and the PAP-3-induced apoptosis was confirmed by annexin V/propidium iodide staining. The apoptosis was involved in mitochondria-mediated pathway including the loss of mitochondrial membrane potential (Δψm), the increase of Bax/Bcl-2 ratio, caspase-9/3 activation, and poly(ADP-ribose) polymerase (PARP) degradation, as well as intracellular ROS production. PAP-3 also induced up-regulation of p53, and cell cycle arrest at the S phase. The incubation of MCF-7 cells with antioxidant superoxide dismutase (SOD) and N-acetylcysteine (NAC) significantly attenuated the ROS generation and apoptosis caused by PAP-3, indicating that intracellular ROS plays a pivotal role in cell death.Conclusions/Significance:These findings suggest that the polysaccharides, especially acidic PAP-3, are very important nutritional ingredients responsible for, at least in part, the anticancer health benefits of P. abalonus via ROS-mediated mitochondrial apoptotic pathway. It is a major breakthrough bringing new insight of the potential use of the polysaccharides as health-care food or medicine to provide significant natural defense against human cancer. © 2013 Shi et al.


Zhao X.Y.,PLA Fourth Military Medical University
Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology | Year: 2013

To evaluate the efficacy of flowable composite resin(FCR) as stress-absorbing liners in Class I cavity restorations in vitro. Thirty Class I cavities of 4 mm in diameter and 2 mm in depth were prepared in polycarbonate (PC) plates and divided into three groups, ten each. After application of an adhesive, cavities in each group were restored using one of the following methods: A: restored with Charisma without any lining of FCR; B: lined with Revolution Formula 2 twice before restoration with Charisma; C: lined with Teric Flow twice before restoration with Charisma. All cavities were observed under a photoelastic microscope and photoelastic images were recorded at 3 min and 24 h after curing and the shrinkage stresses on the cavity wall were calculated. The polymerization shrinkage(v%) of the three composite resins was measured using bonded discs method and their elastic moduli were measured according to ISO standard. The shrinkage stresses at 3 min and 24 h of the three methods were as follows,A: (4.93 ± 0.28), (5.87 ± 0.40) MPa, B: (4.90 ± 0.30), (5.84 ± 0.33) MPa, and C: (4.76 ± 0.28),(5.83 ± 0.37) MPa.No significant difference was found in results among different groups. The polymerization shrinkage(v%) in group A,B, and C were (2.63 ± 0.04)%, (4.56 ± 0.06)%, and (3.98 ± 0.02)%. The elastic modulus in group A, B, and C were (9.59 ± 0.65), (4.25 ± 0.51), and (5.41 ± 0.79) GPa. Under present study condition, using a FCR as stress-absorbing liner under composite resin restoration does not significantly decrease the polymerization shrinkage stresses at the cavity wall.


Li Y.,PLA Fourth Military Medical University
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2013

To investigate the biomechanical properties of porous bioactive bone cement (PBC) in vivo and to observe the degradation of PBC and new bone formation histologically. According to the weight percentage (W/W, %) of polymethylmethacrylate (PMMA) to bioglass to chitosan, 3 kinds of PBS powders were obtained: PBC I (50: 40:10), PBC II (40:50:10), and PBC III (30:60:10). The bilateral femoral condylar defect model (4 mm in diameter and 10 mm in depth) was established in 32 10-month-old New Zealand white rabbits (male or female, weighing 4.0-4.5 kg), which were randomly divided into 4 groups (n = 8); pure PMMA (group A), PBC I (group B), PBC II (group C), and PBC III (group D) were implanted in the bilateral femoral condylar defects, respectively. Gross observation were done after operation. X-ray films were taken after 1 week. At 3 and 6 months after operation, the bone cement specimens were harvested for mechanical test and histological examination. Four kinds of unplanted cement were also used for biomechanical test as control. All rabbits survived to the end of experiment. The X-ray films revealed the location of bone cement was at the right position after 1 week. Before implantation, at 3 months and 6 months after operation, the compressive strength and elastic modulus of groups C and D decreased significantly when compared with those of group A (P < 0.05), but no significant difference was found between groups C and D (P > 0.05); the compressive strength at each time point and elastic modulus at 3 and 6 months of group B decreased significantly when compared with those of group A (P < 0.05). Before implantation and at 3 months after operation, the compressive strength and elastic modulus of groups C and D decreased significantly when compared with those of group B (P < 0.05); at 6 months after operation, the compressive strength of group C and the elastic modulus of group D were significantly lower than those of group B (P < 0.05). The compressive strength and elastic modulus at 3 and 6 months after operation significantly decreased when compared with those before implantation in groups B, C, and D (P < 0.05), but no significant difference was found in group A (P < 0.05). At 3 months after operation, histological observation showed that a fibrous tissue layer formed between the PMMA cement and bone in group A, while chitosan particles degraded with different levels in groups B, C, and D, especially in group D. At 6 months after operation, chitosan particles partly degraded in groups B, C, and D with an amount of new bone ingrowth, and groups C and D was better than group B in bone growth; group A had no obvious change. Quantitative analysis results showed that the bone tissue percentage was gradually increased in the group A to group D, and the bone tissue percentage at 6 months after operation was significantly higher than that at 3 months within the group. According to the weight percentage (W/W, %) of PMMA to bioglass to chitosan, PBCs made by the composition of 40:50:10 and 30:60:10 have better biocompatibility and biomechanical properties than PMMA cement, it may reduce the fracture risk of the adjacent vertebrae after vertebroplasty.


Zhang X.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2011

To construct recombinant plasmid and adenovirus harboring MDA-7 gene, and to investigate its biological function on the proliferation of human hepatocellular carcinoma cells. The MDA-7 fragments from the T vectors were inserted into pCDNA-3 vector to construct expression plasmids named pCDNA3-MDA-7. To determine its effects on the proliferation of HCC cells, transfected the expression vector into cells and tested the ability of colony formation in cancer cells. Simultaneously, constructed recombinant adenovirus expressing MDA-7, and detected its effect on the proliferation of HCC cells by using MTT assay. Successfully constructed plasmid- and adenovirus-based system to express MDA-7. The data of colony formation assay and M'T test showed that MDA-7 can obviously suppress cell growth in HCC cells. MDA-7 may function as tumor suppressor in HCC cells, and the adenovirus-mediated MDA-7 can be a novel strategy for the anti-HCC therapy. Our study established the foundation for future research on the effect of MDA-7 in HCC.


Lau J.Y.W.,Chinese University of Hong Kong | Barkun A.,McGill University | Fan D.-M.,PLA Fourth Military Medical University | Kuipers E.J.,Erasmus University Rotterdam | And 2 more authors.
The Lancet | Year: 2013

Acute upper gastrointestinal bleeding is a common medical emergency worldwide, a major cause of which are bleeding peptic ulcers. Endoscopic treatment and acid suppression with proton-pump inhibitors are cornerstones in the management of the disease, and both treatments have been shown to reduce mortality. The role of emergency surgery continues to diminish. In specialised centres, radiological intervention is increasingly used in patients with severe and recurrent bleeding who do not respond to endoscopic treatment. Despite these advances, mortality from the disorder has remained at around 10%. The disease often occurs in elderly patients with frequent comorbidities who use antiplatelet agents, non-steroidal anti-inflammatory drugs, and anticoagulants. The management of such patients, especially those at high cardiothrombotic risk who are on anticoagulants, is a challenge for clinicians. We summarise the published scientific literature about the management of patients with bleeding peptic ulcers, identify directions for future clinical research, and suggest how mortality can be reduced.


Nie X.W.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2011

To synthesize the minimal and artificial HRE, and to insert it into the anterior extremity of CMV promoter of a AAV plasmid, and then to construct the AAV regulated by hypoxic-responsive element which was introduced into 293 cell by method of Ca3(PO4)2 using three plasmids. Thus obtaining the adenoassociated virus vector regulated by hypoxic-responsive element was possibly used for gene therapy in ischemia angiocardiopathy and cerebrovascular disease. Artificially synthesize the 36 bp nucleotide sequences of four connection in series HIF-binding sites A/GCGTG(4×HBS)and a 35 bp nucleotide sequences spacing inserted into anterior extremity of CMV promoter TATA Box, then amplified by PCR. The cDNA fragment was confirmed to be right by DNA sequencing. Molecular biology routine method was used to construct a AAV vector regulated by minimal hypoxic-responsive element after the normal CMV promoter in AAV vector was replaced by the CMV promoter included minimal hypoxic-responsive element. Then, NT4-6His-PR39 fusogenic peptide was inserted into MCS of the plasmid, the recombinant AAV vector was obtained by three plasmid co-transfection in 293 cells, in which we can also investigate the expression of 6×His using immunochemistry in hypoxia environment. Artificial HRE was inserted into anterior extremity of CMV promoter and there was a correct spacing between the HRE and the TATA-box. The DNA sequencing and restriction enzyme digestion results indicated that the AAV regulated by hypoxic-responsive element was successfully constructed. Compared to the control group, the expressions of 6×His was significantly increased in the experimental groups in hypoxia environment, which confirmed that the AAV effectually regulated by the minimal HRE was inserted into anterior extremity of CMV promoter. The HRE is inserted into anterior extremity of CMV promoter to lack incision enzyme recognition site by PCR. And eukaryotic expression vector regulated by hypoxic-responsive is constructed. The AAV effectually regulated by the minimal HRE inserted into anterior extremity of CMV promoter. The vector is successfully constructed and it has important theoretical and practical value in the synteresis and therapy of ischemia angiocardiopathy and cerebrovascular disease.


Zhang L.-F.,PLA Fourth Military Medical University
European Journal of Applied Physiology | Year: 2013

Evidence from recent ground and spaceflight studies with animals and humans supports the notion that microgravity-induced vascular remodeling contributes to postflight orthostatic intolerance. In the vascular beds of lower body, such as in splanchnic and lower limb circulation, resistance vessels would undergo hypotrophy and decrement in myogenic tone and vasoreactivity. Thus, despite the concurrent sympathetic activation, the increase in peripheral vascular resistance would still be compromised while astronauts were re-exposed to Earth's 1-G gravity, since ∼75 % of the total vascular conductance lies below the heart. On the contrary, cerebral arteries would undergo hypertrophy and vasoreactivity enhancement due to adaptation to cerebral hypertension, which protects the down-stream microcirculation in the brain during spaceflight. However, the enhanced vasoreactivity of cerebral vessels might also aggravate postflight orthostatic intolerance, particularly after long-duration spaceflight. Animal studies have indicated that the underlying mechanisms may involve ion-channel remodeling in vascular smooth muscle cells and vascular NO-NOS and local renin-angiotensin system (L-RAS). Furthermore, vascular remodeling and associated ion-channel and L-RAS changes can be prevented by a countermeasure of daily short-duration restoring to normal standing posture. These findings substantiate in general the hypothesis that redistribution of transmural pressure along the arterial vasculature due to the removal of gravity might be the primary factor that initiates vascular remodeling in microgravity, and daily short-duration restoring its normal distribution by intermittent artificial gravity (IAG) can effectively prevent the vascular adaptation and hence postflight cardiovascular deconditioning. IAG might also be beneficial in maintaining vascular health during future long-duration space flight. © 2013 Springer-Verlag Berlin Heidelberg.


Ji G.,PLA Fourth Military Medical University
International Journal of Obesity | Year: 2016

Background/Objectives:Obesity-related brain structural abnormalities have been reported extensively, and bariatric surgery (BS) is currently the most effective intervention to produce sustained weight reduction in overtly obese (OB) people. It is unknown whether BS can repair the brain circuitry abnormalities concomitantly with long-term weight loss.Subjects/Methods:In order to investigate whether BS promotes neuroplastic structural recovery in morbidly OB patients, we quantified fractional anisotropy (FA), mean diffusivity (MD) and gray (GM) and white (WM) matter densities in 15 morbidly OB patients and in 18 normal weight (NW) individuals. OB patients were studied at baseline and also 1 month after laparoscopic sleeve gastrectomy surgery.Results:Two-sample t-test between OB (baseline) and NW groups showed decreased FA values, GM/WM densities and increased MD value in brain regions associated with food intake control (that is, caudate, orbitofrontal cortex, body and genu of corpus callosum) and cognitive-emotion regulation (that is, inferior frontal gyrus, hippocampus, insula, external capsule) (P<0.05, family-wise error correction). Paired t-test in the OB group between before and after surgery showed that BS generated partial neuroplastic structural recovery in the OB group, but the differences had relative less strength and smaller volume (P<0.001).Conclusions:This study provides the first anatomical evidence for BS-induced acute neuroplastic recovery that might in part mediate the long-term benefit of BS in weight reduction. It also highlights the importance of this line of gut–brain axis research employing the combined BS and neuroimaging model for identifying longitudinal changes in brain structure that correlated with obesity status.International Journal of Obesity advance online publication, 21 June 2016; doi:10.1038/ijo.2016.98. © 2016 Macmillan Publishers Limited


Wang L.,PLA Fourth Military Medical University
The American Journal of dermatopathology | Year: 2010

Spindle cell B-cell lymphoma is a rare morphologic variant of B-cell lymphoma that is generally associated with follicle center cell origin. It is typically found on the skin and presents as single nodule or plaque with a diameter of several centimeters. It is also characterized by abnormal spindle cells with elongated or spindle-shaped nuclei, and usually stained positive for Bcl-6 and negative for multiple myeloma oncogene 1 (MUM-1). In this report, we describe a giant primary cutaneous spindle cell B-cell lymphoma measured 20 cm × 25 cm, substantially larger than all the previously reported cases. Histologic examination revealed that the neoplasm was mainly located in the dermis and subcutaneous fat, and had infiltrated into striated muscles of the patient's back. The neoplasm cells contained elongated or spindle-shaped nuclei. Immunohistochemistry results demonstrated that the neoplasm cells were stained positive for CD20, CD79, and Bcl-6, negative for Bcl-2 and MUM-1, and focally positive for CD5, CD10, CD31, and CD43. These results collectively indicated that the neoplasm was of follicle center cell origin. The neoplasm was excised and the patient was still alive without systemic involvement after 4 years of follow-up.


Li F.,PLA Fourth Military Medical University | Li F.,University of Maryland, Baltimore | Weir M.D.,University of Maryland, Baltimore | Fouad A.F.,University of Maryland, Baltimore | And 2 more authors.
Dental Materials | Year: 2014

Objectives Antibacterial primer and adhesive are promising to inhibit biofilms and caries. Since restorations in vivo are exposed to saliva, one concern is the attenuation of antibacterial activity due to salivary pellicles. The objective of this study was to investigate the effects of salivary pellicles on bonding agents containing a new monomer dimethylaminododecyl methacrylate (DMADDM) or nanoparticles of silver (NAg) against biofilms for the first time. Methods DMADDM and NAg were synthesized and incorporated into Scotchbond Multi-Purpose adhesive and primer. Specimens were either coated or not coated with salivary pellicles. A microcosm biofilm model was used with mixed saliva from ten donors. Two types of culture medium were used: an artificial saliva medium (McBain), and Brain Heart Infusion (BHI) medium without salivary proteins. Metabolic activity, colony-forming units (CFU), and lactic acid production of plaque microcosm biofilms were measured (n = 6). Results Bonding agents containing DMADDM and NAg greatly inhibited biofilm activities, even with salivary pellicles. When using BHI, the pre-coating of salivary pellicles on resin surfaces significantly decreased the antibacterial effect (p < 0.05). When using artificial saliva medium, pre-coating of salivary pellicles on resin did not decrease the antibacterial effect. These results suggest that artificial saliva yielded medium-derived pellicles on resin surfaces, which provided attenuating effects on biofilms similar to salivary pellicles. Compared with the commercial control, the DMADDM-containing bonding agent reduced biofilm CFU by about two orders of magnitude. Significance Novel DMADDM- and NAg-containing bonding agents substantially reduced biofilm growth even with salivary pellicle coating on surfaces, indicating a promising usage in saliva-rich environment. DMADDM and NAg may be useful in a wide range of primers, adhesives and other restoratives to achieve antibacterial and anti-caries capabilities. © 2013 Academy of Dental Materials.


Deng J.,Tianjin Medical University | Liang H.,Tianjin Medical University | Ying G.,Tianjin Medical University | Zhang R.,Tianjin Medical University | And 4 more authors.
Oncotarget | Year: 2014

RNF 180, a novel tumor suppressor, has been implicated in the carcinogenesis and progress of gastric cancer. At present study, we found that lower expression of RNA180 was specific in gastric cancer tissues, and the inconsistently methylated levels of RNF180 promoter were identified in the gastric cancer tissues. Importantly, we demonstrated that the methylated CpG site count and four hypermethylated CpG sites (-116, -80, +97, and +102) were significantly associated with the survival of 400 gastric cancer patients, respectively. With multivariate survival analyses, we demonstrated that both the methylation of combined CpG (-116, -80, +97, and +102) sites and N stage were the independent indictor of prognosis of gastric cancer patients. Eventually, the methylation of combined CpG (-116, -80, +97, and +102) sites was identified to have smaller AIC value than N stage by mean of AIC calculation with the Cox proportional hazards model. These findings indicated that the quantitative detection of RNF180 promoter methylation had the intensive feasibility for evaluation the prognosis of gastric cancer patients in clinic. © 2008-2014 Impact Journals, LLC.


Bai M.,Xijing University | Qi X.-S.,Xijing University | Yang Z.-P.,Xijing University | Yang M.,Xijing University | And 2 more authors.
World Journal of Gastroenterology | Year: 2014

AIM: To compare the liver transplantation-free (LTF) survival rates between patients who underwent transjugular intrahepatic portosystemic shunts (TIPS) and those who underwent paracentesis by an updated meta-analysis that pools the effects of both number of deaths and time to death. METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched from the inception to October 2012. LTF survival, liver transplantation, liver diseaserelated death, non-liver disease-related death, recurrent ascites, hepatic encephalopathy (HE) and severe HE, and hepatorenal syndrome were assessed as outcomes. LTF survival was estimated using a HR with a 95%CI. Other outcomes were estimated using OR with 95%CIs. Sensitivity analyses were performed to assess the effects of potential outliers in the studies according to the risk of bias and the study characteristics. RESULTS: Six randomized controlled trials with 390 patients were included. In comparison to paracentesis, TIPS significantly improved LTF survival (HR = 0.61, 95%CI: 0.46-0.82, P < 0.001). TIPS also significantly decreased liver disease-related death (OR = 0.62, 95%CI: 0.39-0.98, P = 0.04), recurrent ascites (OR = 0.15, 95%CI: 0.09-0.24, P < 0.001) and hepatorenal syndrome (OR = 0.32, 95%CI: 0.12-0.86, P = 0.02). However, TIPS increased the risk of HE (OR = 2.95, 95%CI: 1.87-4.66, P = 0.02) and severe HE (OR = 2.18, 95%CI: 1.27-3.76, P = 0.005). CONCLUSION: TIPS significantly improved the LTF survival of cirrhotic patients with refractory ascites and decreased the risk of recurrent ascites and hepatorenal syndrome with the cost of increased risk of HE compared with paracentesis. Further studies are warranted to validate the survival benefit of TIPS in clinical practice settings. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.


Yao Q.,PLA Fourth Military Medical University
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2011

The purpose of this study was to detect the expression of autophagy-related gene Beclin1 and apoptosis-related genes Bcl-2 and Bax in breast cancer tissues, to investigate their relationship and significance to the occurrence and development of breast cancer, and to provide an experimental basis for the biological treatment of breast cancer in the future. Human breast cancer tissues and relatively healthy breast tissue adjacent to the tumor were collected during surgical resection. By using RT-PCR and western blot, the mRNA and protein expressions of Beclin1, Bcl-2, and Bax were detected in the breast cancer tissues and the relatively healthy, adjacent tissues. The correlations of these expressions with the occurrence, development, and clinicopathology of breast cancer were analyzed. The mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues were significantly lower than those in the relatively healthy, adjacent breast tissues (p < 0.05); the lower the degree of tumor differentiation, the lower the mRNA and protein expressions of Beclin1 and Bcl-2 (p < 0.05); the mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues from patients positive for lymph node metastasis were significantly lower than those negative for lymph node metastasis (p < 0.05); the mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues from patients positive for distant metastasis were significantly lower than those negative for distant metastasis (p < 0.05); the mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues from patients positive for ki67 were significantly lower than those negative for ki67 (p < 0.05). The mRNA and protein expressions of Bax were different from those of Beclin1 and Bcl-2. In breast cancer tissues, the mRNA and protein expressions of Bax were up-regulated (p < 0.05); the lower the degree of tumor differentiation, the higher the mRNA and protein expressions of Bax (p < 0.05); the mRNA and protein expressions of Bax in breast cancer tissues from patients positive for lymph node metastasis were significantly higher than those negative for lymph node metastasis (p < 0.05); and the mRNA and protein expressions of Bax in breast cancer tissues from patients positive for distant metastasis were significantly higher than those in patients negative for distant metastasis (p < 0.05). However, the mRNA and protein expressions of these three genes were not correlated with patient age, tumor size, progesterone receptor positivity, or human epidermal growth factor positivity (p > 0.05). The correlation of Bcl-2 and Bax mRNA with Beclin1 mRNA expressed in breast cancer tissues were both statistically significant (p < 0.05). The activity change of autophagy and apoptosis is associated with the tumorigenesis and tumor progression of breast cancer. The joint detection of these three genes (Beclin1, Bcl-2, and Bax) contributes to the early diagnosis of and predicts prognosis for breast cancer, and this also provides an experimental basis for the biological therapy of breast cancer.


Zhao Y.-Y.,Northwest University, China | Shen X.,PLA Fourth Military Medical University | Cheng X.-L.,National Institutes for Food and Drug Control | Wei F.,National Institutes for Food and Drug Control | And 2 more authors.
Process Biochemistry | Year: 2012

Ergosta-4,6,8(14),22-tetraen-3-one (ergone), isolated from the medicinal fungus Polyporus umbellatus, has been proven to prevent the progression of renal injury and the subsequent renal fibrosis. UPLC Q-TOF/MS was employed to investigate the metabonomic characteristics of adenine-induced chronic renal failure (CRF) and the proactive effects of ergone. The significant difference of the metabolic profiling was observed from ergone-treated group compared with the CRF model group during the 10-day and 20-day study periods by using the principal components analysis (PCA). The significant difference of the ergone-treated group in metabolic profiling was also observed between 10-day and 20-day study periods. The time-dependent tendency in ergone-treated group from day 10 to 20 was obtained, indicating the time-dependent recovery effect of ergone on CRF rats. Some significantly changed metabolites like creatinine, proline, adrenosterone, taurine, creatine, phenylalanine, ornithine, dopamine, kynurenine, kynurenic acid and 3-O-methyldopa have been identified during the 20-day study period. These biochemical changes are related to the disturbance in energy metabolism and amino acid metabolism, which are helpful to further understand the CRF and the therapeutic mechanism of ergone. This work suggests that this metabonomic approach could be used as a potentially powerful tool to investigate the biochemical changes of certain physiopathological conditions, such as metabolic syndrome, as an early diagnostic measure. © 2012 Elsevier Ltd.


Xing H.,PLA Fourth Military Medical University | Taguchi Y.,Osaka Dental University | Sekino T.,Tohoku University
International Journal of Nanomedicine | Year: 2014

Background: Titanium surfaces play an important role in affecting osseointegration of dental implants. Previous studies have shown that the titania nanotube promotes osseointegration by enhancing osteogenic differentiation. Only relatively recently have the effects of titanium surfaces with other nanostructures on osteogenic differentiation been investigated. Methods: In this study, we used NaOH solutions with concentrations of 2.5, 5.0, 7.5, 10.0, and 12.5 M to develop a simple and useful titanium surface modification that introduces the nanonetwork structures with titania nanosheet (TNS) nanofeatures to the surface of titanium disks. The effects of such a modified nanonetwork structure, with different alkaline concentrations on the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMMSCs), were evaluated. Results: The nanonetwork structures with TNS nanofeatures induced by alkali etching markedly enhanced BMMSC functions of cell adhesion and osteogenesis-related gene expression, and other cell behaviors such as proliferation, alkaline phosphatase activity, extracellular matrix deposition, and mineralization were also significantly increased. These effects were most pronounced when the concentration of NaOH was 10.0 M. Conclusion: The results suggest that nanonetwork structures with TNS nanofeatures improved BMMSC proliferation and induced BMMSC osteogenic differentiation. In addition, the surfaces formed with 10.0 M NaOH suggest the potential to improve the clinical performance of dental implants. © 2014 Xing et al.


Pan Z.J.,PLA Fourth Military Medical University
Zhongguo gu shang = China journal of orthopaedics and traumatology | Year: 2013

To research many clinical data of nonunion cases and discover the reasons for low capacity of bone growth. From October 1999 to April 2009,the source material of 280 nonunion cases were conducted and followed up. The data of the study included 230 males and 50 females,with an average age of 39.4 years old ranging from 19 to 62 years. The fracture position was femur in 129 cases,tibia in 83 cases,humerus in 47 cases, feet radius bone in 21 cases, the ratio was 46:29.6:16.8:7.5. The survey included primary injury process,damage degree and the effect of first treatment,hospital level of first treatment,timing of surgery for the first time, the early callus growth conditions and whether there were obvious technical errors. There were 129 femoral nonunion cases with complete data,121 cases derived from closed fractures, 8 cases from open fractures; 111 cases was aseptic nonunion. 90% of femoral aseptic nonunion had no obvious callus growth, 80% of first treatment performed intraday surgical internal fixation, 10% were undergone operation within three days and 90% was early surgery totally. Low quality of bone callus growth is the main reason for current nonunion and the early surgical fixation has much to do with low quality of bone callus growth.


Zhou X.-H.,PLA Fourth Military Medical University
Modern Physics Letters B | Year: 2010

The shapes of DNA, carbon nanotube (CNT) and vesicle are determined by the minimum of their elastic energy. Two central results about the low-dimensional elastic structure are reported here. Firstly, if the energy density of a one-dimensional structure is only related to its curvature, we generally find that a helix solution with the helix angle θ = ±π/4 will have zero total energy. Secondly, with the fixed length and radii, the helical multi-walled carbon nanotubes (MWNTs) and DNA will have the lowest energy when the helix angle θ = ±π/3. © 2010 World Scientific Publishing Company.


Ye R.,Xijing Hospital | Yang Q.,Xijing Hospital | Kong X.,PLA Fourth Military Medical University | Li N.,Xijing Hospital | And 5 more authors.
Critical Care Medicine | Year: 2012

Objective: Anesthetic preconditioning appears to be a viable strategy to treat ischemic cerebral injury. Here we investigated 1) whether the protection conferred by sevoflurane preconditioning sustains in time; 2) whether sevoflurane preconditioning diminishes mitochondrial dysfunction following cerebral ischemia; and 3) whether mitochondrial permeability transition pore plays a crucial role in the sevoflurane preconditioning. Design: Laboratory investigation. Setting: University research laboratory. Subjects: Sprague-Dawley rats. Interventions: Rats underwent 2 hrs of focal cerebral ischemia induced by middle cerebral artery occlusion. Preconditioning was elicited with sevoflurane (2.3%) for 60 mins at 24 hrs before ischemia. The involvement of mitochondrial permeability transition pore was determined with a mitochondrial permeability transition pore opener atractyloside and a specific mitochondrial permeability transition pore inhibitor cyclosporin A. In vitro study was performed on acutely isolated mitochondria subjected to calcium overload. Measurements and Main Results: Sevoflurane preconditioning significantly decreased the infarct size by 35.9% (95% confidence interval 6.5-28.4, p < .001). This reduction of injury volume was associated with a long-term improvement of neurological function according to modified neurological severity score (F = 13.6, p = .001) and sticky-tape test (F = 29.1, p < .001) for 42 days after ischemia. Furthermore, sevoflurane preconditioning markedly protected mitochondria, as indicated by preserved respiratory chain complex activities and membrane potential, lowered mitochondrial hydrogen-peroxide production, and attenuated mitochondrial permeability transition pore opening. Isolated mitochondria also demonstrated a reduced sensitivity to Ca-induced mitochondrial permeability transition pore opening after pre-exposure to sevoflurane in vitro (95% confidence interval 24.2-196.5,p = .006). Inhibiting mitochondrial permeability transition pore using cyclosporin A resulted in protective effects similar to those seen with sevoflurane preconditioning, whereas pharmacologically opening the mitochondrial permeability transition pore with atractyloside abrogated all the positive effects of sevoflurane preconditioning and cyclosporin A, including suppression of mitochondrial permeability transition pore opening, counteraction of mitochondria-dependent apoptotic pathway, and subsequent histological and behavioral improvements. Conclusions: Sevoflurane preconditioning protects mitochondria from cerebral ischemia/reperfusion injury and ameliorates long-term neurological deficits. Inhibition of mitochondrial permeability transition pore opening is a crucial step in mediating the neuroprotection of sevoflurane preconditioning. © 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.


Gibson S.A.,University of Aberdeen | Gao G.-D.,PLA Fourth Military Medical University | McDonagh K.,National University of Ireland | Shen S.,National University of Ireland
Stem Cell Research and Therapy | Year: 2012

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive accumulation of Lewy body inclusions along with selective destruction of dopaminergic (DA) neurons in the nigrostriatal tract of the brain. Genetic studies have revealed much about the pathophysiology of PD, enabling the identification of both biomarkers for diagnosis and genetic targets for therapeutic treatment, which are evolved in tandem with the development of stem cell technologies. The discovery of induced pluripotent stem (iPS) cells facilitates the derivation of stem cells from adult somatic cells for personalized treatment and thus overcomes not only the limited availability of human embryonic stem cells but also ethical concerns surrounding their use. Non-viral, non-integration, or non-DNA-mediated reprogramming technologies are being developed. Protocols for generating midbrain DA neurons are undergoing constant refinement. The iPS cell-derived DA neurons provide cellular models for investigating disease progression in vitro and for screening molecules of novel therapeutic potential and have beneficial effects on improving the behavior of parkinsonian animals. Further progress in the development of safer non-viral/non-biased reprogramming strategies and the subsequent generation of homogenous midbrain DA neurons shall pave the way for clinical trials. A combined approach of drugs, cell replacement, and gene therapy to stop disease progression and to improve treatment may soon be within our reach. © 2012 BioMed Central Ltd.


Liu Y.,Jiujiang University | Wang L.,PLA Fourth Military Medical University
Journal of Cutaneous Pathology | Year: 2012

Subungual melanoma commonly presents with solitary longitudinal melanonychia. Herein, we report the case of a patient with subungual melanoma who developed involvement of three digits by three independent primary melanomas. A 98-year-old male patient presented with a two-year history of longitudinal melanonychia on three different fingernails. Histopathologically, all three lesions were proved to be melanoma. To our knowledge, this is the first reported case in which three subungual melanomas developed in one patient. Our case indicates that that not all examples of multiple longitudinal melanonychia represent benign lesions. Copyright © 2012 John Wiley & Sons A/S.


Xu P.T.,PLA Fourth Military Medical University
Sheng li xue bao : [Acta physiologica Sinica] | Year: 2010

The aim of the present study was to investigate the expressions of calpain and calpastatin in the myocardium of simulated weightlessness rats, and to elucidate the underlying mechanism of cardiac troponin I (cTnI) degradations. Tail-suspended (SUS) rats were used as a simulated weightlessness model on the ground. The myocardium of rats was homogenized, and the expressions of calpain-1, calpain-2, calpastatin and cTnI were analyzed by Western blotting technique. Calpastatin expression was significantly decreased in 2- and 4-week SUS groups compared with that in the synchronous controls (P<0.05). Calpain-2 expression was slightly decreased, whereas calpain-1 expression was unaltered in SUS groups. However, calpain-1/calpastatin and calpain-2/calpastatin ratios were increased after tail-suspension, being significantly higher in 2- and 4-week SUS groups than those in the synchronous controls (P<0.05, P<0.01). Cardiac TnI degradation was significantly increased after tail-suspension (P<0.01), but cTnI degradation in both SUS and control groups was significantly inhibited by a non-specific inhibitor of calpain, PD150606 (P<0.01). These results suggest that an increase in calpain activity may enhance cTnI degradation in the myocardium of tail-suspended rats.


Zhou X.-H.,PLA Fourth Military Medical University
International Journal of Modern Physics B | Year: 2010

DNA's shape mostly lies on its total energy F. Its corresponding equilibrium shape equations can be obtained by classical variation method: letting the first energy variation δ(1)F = 0. Here, we not only provide the first variation δ(1)F but also give the second variation δ(2)F in planar case. Moreover, the general shape equations of DNA are abstained and a mistake in Zhang et al., [Phys. Rev. E 70, 051902 (2004)] is pointed out. © 2010 World Scientific Publishing Company.


Wang Y.C.,PLA Fourth Military Medical University
Biochemistry and cell biology = Biochimie et biologie cellulaire | Year: 2013

Individuals exposed to extended periods of spaceflight or prolonged 6° head-down-tilt bed rest often suffer from health hazards represented by cardiovascular deconditioning. Many studies have reported that alterations in vascular endothelial cells contribute to cardiovascular dysfunction induced by microgravity. Autophagy, a lysosomal degradation pathway, serves an adaptive role for survival, differentiation, and development in cellular homeostasis, and can be triggered by various environmental stimuli. However, whether autophagy can be induced in endothelial cells by real or simulated microgravity remains to be determined. This study was designed to investigate the effects of simulated microgravity on the activation of autophagy in human umbilical vein endothelial cells (HUVECs). We report here that clinorotation, a simulated model of microgravity, enhances autophagosome formation, increases LC3 and beclin-1 expression, and promotes the conversion of LC3-I to LC3-II in HUVECs. These results demonstrate that simulated microgravity for 48 h activates autophagy of vascular endothelial cells.


Zhang J.,University of Houston | Zhang J.,PLA Fourth Military Medical University | Chang B.,University of Houston | Chang B.,Fudan University | And 2 more authors.
Human Pathology | Year: 2013

Single-chain glycoprotein CD44 is a major cell surface receptor for hyaluronan and mediates epithelial cell adhesion by its involvement in cell-cell and cell-matrix interactions. Recently, CD44 has been identified as a biomarker of cancer stem cells in many malignancies including ovarian carcinoma. However, its clinical significance in human ovarian carcinoma has been controversial until recently. The aim of our current study was to clarify the clinical role of CD44 expression in human ovarian carcinoma. Immunohistochemical staining of 483 primary ovarian carcinoma and 27 paired primary and recurrent ovarian carcinoma samples for CD44 standard form (CD44s) was performed using tissue microarray. The associations between CD44s expression and clinical factors (histologic types, tumor grade, International Federation of Gynecology and Obstetrics stage, and response to chemotherapy), and overall or disease-free survivals were analyzed. We observed CD44s expression in 38% of the ovarian carcinoma samples. Results of the Fisher exact test suggested that CD44s expression was associated with high-grade carcinoma (P =.013), advanced International Federation of Gynecology and Obstetrics stage (III-IV; P <.001), age at diagnosis less than 60 years (P =.011), and transitional cell carcinoma (P =.039). However, CD44s expression was not associated with overall survival (P =.529) or disease-free survival (P =.218) by the log-rank test. Moreover, there was no statistical difference in CD44s expression between the primary and recurrent ovarian carcinomas. Our results showed that CD44s expression is not a prognostic predictor in ovarian cancer. © 2013 Elsevier Inc.


Wang K.,Xian Jiaotong University | Fu Q.,Xian Jiaotong University | Chen X.,PLA Fourth Military Medical University | Gao Y.,Xian Jiaotong University | Dong K.,Xian Jiaotong University
RSC Advances | Year: 2012

In this paper, a new kind of pH-sensitive hydrogel based on poly(lactic acid) (PLA), methoxyl poly(ethylene glycol) (MPEG) and itaconic acid (IA) was prepared by heat-initiated free radical polymerization method without any organic solvent. The obtained macromonomers and hydrogels were characterized by 1H NMR and FTIR. Detailed swelling behavior of hydrogels under variational pH-conditions revealed that the dynamic sensitivity of P(MPEG-PLA-co-IA-MEGMA) hydrogels [P(LE-IA-MEG) hydrogels] as well as the diffusional mechanisms might be causing the network expansion and collapse. In vitro drug release behavior was investigated using VB 12 and paclitaxel (PTX) as model drugs, revealing that the P(LE-IA-MEG) hydrogel could control the diffusion of the drug. The prepared new kind of pH-sensitive hydrogel with great pH-responsiveness and good properties for drug delivery might have great potential application in smart drug delivery systems. This journal is © 2012 The Royal Society of Chemistry.


The proliferation, migration, and adhesion of vascular smooth muscle cells (VSMCs) and their interactions with extracellular matrix are key features of atherosclerosis and restenosis. Recently, there has been evidence that magnetic fields exert multiple effects on the biological performance of cells and may aid in the treatment of vascular disease. However, the effect of a static magnetic field (SMF) on human VSMCs still remains unknown. In this study, we aimed to determine the effects of low strength SMF on human VSMCs in an in vitro restenosis model. A SMF was established using neodymium-yttrium-iron permanent magnet. Human umbilical artery smooth muscle cells (hUASMCs) were isolated and seeded to a fibronectin-coated plate to form an in vitro restenosis model and then exposed to a vertically oriented field of 5 militesla (mT). MTT, transwell, and adhesion assays were used to demonstrate that the proliferation, migration, and adhesion potential of hUASMCs were significantly decreased after exposure to 5 mT SMF for 48 h compared with a non-treated group. Meanwhile, confocal microscopy analysis was used to demonstrate that integrin β(1) clustering was inhibited by exposure to 5 mT SMF. Furthermore, the phosphorylation of focal adhesion kinase (FAK) was markedly inhibited, and the upregulated cytosolic free calcium had been reversed (p < 0.05). However, the biological effects of low strength SMF on hUASMCs could be blocked by the administration of GRGDSP-the blockade of integrins. In conclusion, a low strength SMF can influence the proliferation, migration, and adhesion of VSMCs by inhibiting the clustering of integrin β1, decreasing cytosolic free calcium concentration, and inactivating FAK. With further validation, SMFs may aid in attenuating abnormal VSMCs biological performance and has potential to block atherogenesis and prevent restenosis.


To examine the effect of decreased estrogen level and altered diet hardness on condylar cartilage morphology of the rat temporomandibular joint (TMJ) and on the expression of condylar cartilage estrogen receptor alpha (ERa) and matrix metalloproteinase-8 (MMP-8). A total of 36 female rats was divided into four groups: ovariectomized rats fed a normal diet, non-ovariectomized controls fed a normal diet, ovariectomized rats fed a soft diet, and non-ovariectomized controls fed a soft diet. Ovariectomy was performed at the age of 60 days. Seven days after the operation, the rats were sacrificed. Repeated measures ANOVA and Duncan's multiple comparison tests were used for statistical analysis. The ovariectomized rats had thicker cartilage layers than the controls, both in the normal diet and soft diet groups. The thinnest cartilage layers were found in the control rats fed with the soft diet. The thickness of the chondroblastic layer was significantly higher (P < .001) in the normal-diet rats than in the soft-diet rats in both ovariectomized and non-ovariectomized groups. The thickness of the proliferative layer was significantly higher (P < .001) in the ovariectomized soft-diet rats than in the soft-diet control rats. The proportional amount of ERa was statistically significantly higher (P < .001) in the condylar cartilage of the ovariectomized rats than in the non-ovariectomized control rats both in the normal- and soft-diet groups. The proportional amount of ERa was statistically significantly higher (P < .001) in the ovariectomized normal-diet rats than in the ovariectomized soft-diet rats. The proportional number of MMP-8-positive cells was statistically significantly higher (P < .001) in the condylar cartilage of ovariectomized rats fed the soft diet than in non-ovariectomized control rats fed the soft diet. Control rats fed with the normal diet had a higher proportional amount of MMP-8 positive cells than control rats fed with the soft diet (P < .05). The rat TMJ condylar cartilage is sensitive to changes in estrogen levels and altered diet hardness.


Wang L.,PLA Fourth Military Medical University
European journal of histochemistry : EJH | Year: 2012

The polarized molecules predominately distributing at hepatocyte canalicular surface play a vital role in disclosing the process of bile formation and etiopathogenisis of cholestatic live diseases. Therefore, it is important to find novel polarized molecules on hepatocyte canalicular membrane. In the present study, canalicular membrane vesicles (CMVs) isolated from rat hepatocyte by density gradient centrifugation were used as immunogens to produce hybridoma and 46 strains of monoclonal antibodies (mAb) against CMVs were obtained. With a series of morphological assay methods, including immunohistochemistry, immunofluorescence and immuno-electron microscope, the antigens recognized by canalicular mAb1 (CM1) and canalicular mAb2 (CM2) were confirmed to predominately distribute at hepatocyte canalicular membrane. Transport activity assay revealed that CM2 could inhibit ATP-dependent E217βG uptake of rat hepatocyte CMVs. Meanwhile, Western blotting analysis showed that the molecular mass of CM2 antigen was approximately 110kDa, which was much less than Mr 180kDa of multidrug resistance-associated protein 2 (MRP2) involved in glucuronide transport. These data indicated that CM2 antigen might be a potential novel molecule participating in glucuronide transport on the hepatocyte canalicular membrane.


Zhou H.,University of Maryland, Baltimore | Zhou H.,PLA Fourth Military Medical University | Chen W.,University of Maryland, Baltimore | Weir M.D.,University of Maryland, Baltimore | And 2 more authors.
Tissue Engineering - Part A | Year: 2012

Stem cell-encapsulating microbeads could be mixed into a paste such as calcium phosphate cement (CPC), where the microbeads could protect the cells from the mixing and injection forces. After being placed, the microbeads could quickly degrade to release the cells throughout the scaffold, while creating macropores. The objectives of this study were to (1) construct alginate-fibrin microbeads encapsulating human umbilical cord mesenchymal stem cells (hUCMSCs) embedded in the surface of novel biofunctionalized CPC and (2) investigate microbead degradation, cell release, and osteodifferentiation on CPC. Hydrogel microbeads were fabricated that encapsulated hUCMSCs at 1×106 cells/mL. CPC was biofunctionalized with fibronectin (Fn) and Arg-Gly-Asp (RGD). Four scaffolds were tested: CPC control, CPC mixed with Fn, CPC mixed with RGD, and CPC grafted with RGD. The degradable microbeads released hUCMSCs at 7 days, which attached to CPC. Adding Fn or RGD to CPC greatly improved cell attachment. CPC grafted with RGD showed the fastest cell proliferation, with cell density being ninefold that on CPC control. The released hUCMSCs underwent osteodifferentiation. Alkaline phosphatase, osteocalcin, collagen 1, and runt-related transcription factor 2 (Runx2) gene expression increased by 10 to 30 fold at 7-21 days, compared with day 1. The released cells on CPC synthesized bone minerals, with the mineralization amount at 21 days being two orders of magnitude higher than that at 7 days. In conclusion, alginate-fibrin microbeads embedded in CPC surface were able to quickly release the hUCMSCs that attached to biofunctionalized CPC. Incorporating Fn and RGD into CPC greatly improved cell function, and CPC grafted with RGD had the fastest cell proliferation. The released cells on CPC differentiated into the osteogenic lineage and synthesized bone minerals. The new biofunctionalized CPC with hUCMSC-encapsulating microbeads is promising for bone regeneration applications. © 2012 Copyright, Mary Ann Liebert, Inc.


Yu Y.,PLA Fourth Military Medical University | Wang W.,Xian Jiaotong University | Zhai S.,Xian Jiaotong University | Dang S.,Xian Jiaotong University | Sun M.,Xian Jiaotong University
Molecular Biology Reports | Year: 2012

A number of case-control studies were conducted to investigate the association of IL6 gene polymorphisms with colorectal cancer (CRC). However, the results were not always consistent. We performed a systematic review and meta-analysis to examine the association between the IL6 gene polymorphisms and CRC. Data were collected from the following electronic databases: PubMed, EMBASE, Web of Science, BIOSIS Previews, HuGENet, and Chinese Biomedical Literature Database, with the last report up to July 2011. A total of 17 studies involving 4 SNPs were included (16 for rs1800795, 2 for rs1800796, 2 for rs1800797, and 1 for rs13306435). Overall, no significant association of these polymorphisms with CRC was found in heterozygote comparisons as well as homozygote comparison, dominant genetic model and recessive model. In subgroup analysis, among studies using population-based controls, fulfilling Hardy-Weinberg equilibrium, or using Taqman genotyping method, we did not find any significant association. However, the rs1800795 C allele was significantly associated with reduced risk for CRC among persons who regularly or currently took NSAIDs (four studies, OR = 0.750; 95 % CI, 0.64-0.88; P = 0.474 for heterogeneity test), and with increased risk for CRC among persons who drank (one study, OR = 1.97; 95 % CI, 1.32-2.94). Individuals with the rs1800795 C allele in the IL6 gene have a significantly lower risk of CRC, but in the setting of NSAIDs use. Further studies are merited to assess the association between the IL6 gene polymorphisms and CRC risk among persons who take NSAIDs, drink or smoke, etc. © 2012 Springer Science+Business Media B.V.


Hui Y.-N.,PLA Fourth Military Medical University
Ophthalmology in China | Year: 2013

Macular holes are one of main reasons for visual loss and primarily occur in eyes with high myopia and otherwise healthy eyes of aging people. In the latter situation, it has been recognized as "idiopathic senile macular hole". In recent years, spectral-domain optical coherence tomography (OCT) has revealed the relationship of development of macular hole with perifoveal posterior vitreous detachment (PVD). It can be reasonably convinced that vitreous liquefaction and incomplete PVD on the maculae is the primary cause in pathogenesis of macular hole. It is therefore suggested that these two common types of macular holes can be defined as "myopic and senile macular holes, respectively. It should be recommended that routine examination with OCT applied on the corresponding eyes may benefit to prevent and treat macular hole. (Ophthalmol CHN, 2013, 22: 217-219). Copyright © 2013 by the Editorial Board of OPHTHALMOLOGY IN CHINA.


Liu Y.,PLA Fourth Military Medical University | Liu Y.,Emory University | Sun S.-Y.,Emory University | Owonikoko T.K.,Emory University | And 4 more authors.
Molecular Cancer Therapeutics | Year: 2012

Inhibition of mTOR signaling by rapamycin has been shown to activate extracellular signal-regulated kinase 1 or 2 (ERK1/2) and Akt in various types of cancer cells, which contributes to rapamycin resistance. However, the downstream effect of rapamycin-activated ERKs and Akt on survival or death substrate(s) remains unclear. We discovered that treatment of human lung cancer cells with rapamycin results in enhanced phosphorylation of Bad at serine (S) 112 and S136 but not S155 in association with activation of ERK1/2 and Akt. A higher level of Bad phosphorylation was observed in rapamycin-resistant cells compared with parental rapamycin-sensitive cells. Thus, Bad phosphorylation may contribute to rapamycin resistance. Mechanistically, rapamycin promotes Bad accumulation in the cytosol, enhances Bad/14-3-3 interaction, and reduces Bad/Bcl-XL binding. Rapamycin-induced Bad phosphorylation promotes its ubiquitination and degradation, with a significant reduction of its half-life (i.e., from 53.3-37.5 hours). Inhibition of MEK/ERK by PD98059 or depletion of Akt by RNA interference blocks rapamycin-induced Bad phosphorylation at S112 or S136, respectively. Simultaneous blockage of S112 and S136 phosphorylation of Bad by PD98059 and silencing of Akt significantly enhances rapamycin-induced growth inhibition in vitro and synergistically increases the antitumor efficacy of rapamycin in lung cancer xenografts. Intriguingly, either suppression of Bad phosphorylation at S112 and S136 sites or expression of the nonphosphorylatable Bad mutant (S112A/S136A) can reverse rapamycin resistance. These findings uncover a novel mechanism of rapamycin resistance, which may promote the development of new strategies for overcoming rapamycin resistance by manipulating Bad phosphorylation at S112 and S136 in human lung cancer. ©2011 AACR.


Liu J.,China University of Petroleum - East China | Xia R.,Wuhan University | Zhou X.,PLA Fourth Military Medical University
Science China: Physics, Mechanics and Astronomy | Year: 2012

In this study, we considered the wetting phenomenon on a general substrate from a new viewpoint of continuum mechanics. The analyses first show how the Wenzel and the Cassie models deviate the practical results in some special substrates, and then elucidate the mechanism of the triple contact line (TCL) moving. Based upon variational theory of the total free functional dealing with the movable boundary condition, we show that the macroscopic contact angle (MCA) expression is the corresponding transversality condition. It manifests that the MCA depends only on the chemical and geometric property at the TCL, and is not affected by the gravity of the droplet and the contact area beneath the liquid. Our continuum model also shows the exploration of the pinning effect on a sharp wedge or the interface between two different phases. This investigation will help designing super-hydrophobic materials for novel micro-fluidic devices. © Science China Press and Springer-Verlag Berlin Heidelberg 2012.


Dysregulation of transcription factors (TFs) is associated with tumor progression, but little is known about TF expression patterns in the context of gastric cancer (GC) metastasis. Using array-based profile analysis, we found that 22 TFs showed differential activities between GC cell lines with low- and high-metastatic potential. Of this group of TFs, serum response factor (SRF) was significantly upregulated in metastatic GC cells. SRF expression was frequently elevated in a panel of metastatic GC cells and tissues, and high-level expression of SRF was significantly associated with a more aggressive phenotype and poor prognosis in patients with GC. In GC cell lines, overexpression of SRF potently promoted cell migration and invasion in vitro as well as the formation of intrahepatic and pulmonary metastases in vivo, whereas loss of SRF inhibited GC cell invasion and metastasis. We also performed a microRNA microarray to screen for transcriptional targets of SRF and found that SRF transactivates miR-199a-5p and miR-199a-3p by directly binding to their promoters. We further determined that overexpression of miR-199a-5p, but not miR-199a-3p, increased GC cell invasion and metastasis. In contrast, inhibition of miR-199a-5p impaired the metastatic potential of GC cells in vitro and in vivo, and E-cadherin was identified as a direct and functional target of miR-199a-5p in GC cells. Specifically, our results showed that SRF promotes GC metastasis and the epithelial to mesenchymal transition (EMT) though miR-199a-5p-mediated downregulation of E-cadherin. The present study thus provides insight into the specific biological behavior of SRF in GC metastasis. As increased activity of the SRF/miR-199a-5p/E-cadherin pathway appears to promote GC cell EMT and metastasis, these regulators may therefore be developed as therapeutic targets or biomarkers for GC progression.Cell Death and Differentiation advance online publication, 1 August 2014; doi:10.1038/cdd.2014.109.


Lu X.,Shaanxi Normal University | Zhao Y.,PLA Fourth Military Medical University | Sun Y.,Shaanxi Normal University | Yang S.,Shaanxi Normal University | Yang X.,Shaanxi Normal University
Food Chemistry | Year: 2013

This study was to examine the hepatoprotective effects of polysaccharides from green tea of Huangshan Maofeng (HMTP) against CCl4-induced oxidative damage in mice. HMTP is an acidic heteropolysaccharide with galactose (35.0%, mol.%), arabinose (28.9%) and galacturonic acid (11.3%) being the main monosaccharide components. HMTP (400 and 800 mg/kg·bw) administered orally daily for 14 days before CCl4 administration significantly reduced the impact of CCl4 toxicity on the serum markers of liver damage, alanine aminotransferase, aspartate aminotransferase, total-cholesterol and triglycerides. This method of HMTP administration also markedly restrained hepatic lipid peroxidation formation of malondialdehyde and 15-F2t isoprostanes, and elevated the antioxidant levels of hepatic glutathione and superoxide dismutase. These results together with liver histopathology indicated that HMTP exhibited hepatoprotection against CCl4-induced injury, which was found to be comparable to that of biphenyldicarboxylate. The hepatoprotective effects of HMTP may be due to both the inhibition of lipid peroxidation and the increase of antioxidant activity. © 2013 Elsevier Ltd. All rights reserved.


Mani S.,Lakehead University | Cao W.,Lakehead University | Cao W.,Thunder Bay Regional Research Institute | Cao W.,PLA Fourth Military Medical University | And 3 more authors.
Nitric Oxide - Biology and Chemistry | Year: 2014

Hydrogen sulfide (H2S) is a gasotransmitter that regulates numerous physiological and pathophysiological processes in our body. Enzymatic production of H2S is catalyzed by cystathionine c-lyase (CSE), cystathionine b-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MST). All these three enzymes present in the liver and via H2S production regulate liver functions. The liver is the hub for metabolism of glucose and lipids, and maintains the level of circulatory lipids through lipoprotein metabolism. Hepatic H2S metabolism affects glucose metabolism, insulin sensitivity, lipoprotein synthesis, mitochondrial biogenetics and biogenesis. Malfunction of hepatic H2S metabolism may be involved in many liver diseases, such as hepatic fibrosis and hepatic cirrhosis. © 2014 Elsevier Inc. All rights reserved.


Yang X.,Shaanxi Normal University | Yang S.,Shaanxi Normal University | Guo Y.,Shaanxi Normal University | Jiao Y.,Shaanxi Normal University | Zhao Y.,PLA Fourth Military Medical University
Food Chemistry | Year: 2013

Water-soluble apple peel polysaccharides (APP) and apple flesh polysaccharides (AFP) were isolated from Pink Lady fruits, and their in vitro antioxidant capacities were characterised by DPPH, HO, and O2 - systems, and ferric-reducing antioxidant power assay. Oral administration of APP at 250 and 500 mg/kg bw in mice was shown to be as effective as AFP in lowering the CCl4-caused increases of serum alanine aminotransferase, aspartate aminotransferase and lactic dehydrogenase activities, and hepatic malondialdehyde level, and antagonising the decreases in antioxidant superoxide dismutase and glutathione peroxidase activities caused by CCl4 (p < 0.05). Histopathological examinations further confirmed that both APP and AFP could protect the liver from CCl 4-induced histological alteration. HPLC analysis also showed similar profiles of monosaccharide composition for APP and AFP with arabinose, galactose and galacturonic acid being main component monosaccharides. All of these findings demonstrate that the extracts of both APP and AFP possess antioxidant and hepatoprotective potential. © 2012 Elsevier Ltd. All rights reserved.


Wang D.,Shaanxi Normal University | Zhao Y.,PLA Fourth Military Medical University | Jiao Y.,Shaanxi Normal University | Yu L.,Shaanxi Normal University | And 2 more authors.
Carbohydrate Polymers | Year: 2012

This study was designed to characterize the chemical composition, antioxidant activity and hepatoprotective effect of the polysaccharides from Zizyphus jujube cv. Shaanbeitanzao (ZSP). HPLC analysis showed that ZSP was the heteropolysaccharides with l-arabinose being the main component monosaccharide (50.2%, molar percentage). ZSP displayed strong antioxidant activity in vitro, and the effect was further verified by suppressing CCl 4-induced oxidative stress in liver at three tested doses of ZSP (100, 200, and 400 mg/kg BW) in mice. Administration of ZSP (400 mg/kg) significantly (p < 0.01) reduced the activities of CCl 4-elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactic dehydrogenase (LDH) in serum, and hepatic malondialdehyde (MDA) level. Mice treated with ZSP showed a better profile of hepatosomatic index (HI) and antioxidant system with normal glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities in liver. These results suggest that ZSP exerts an effective protection against CCl 4-induced hepatic injury by mediating antioxidative and free radical scavenging activities. © 2012 Elsevier Ltd. All rights reserved.


Zhou Y.,PLA Fourth Military Medical University
Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology | Year: 2010

To observe the effects of repeated + Gz exposures on the apoptosis of myocyte in rats. Twelve male Sprague-Dawley rats were randomly divided into three groups: Control group, + 6Gz group and + 10Gz group. The rats of + Gz groups were exposed to + 6Gz for 3 min, + 10Gz for 3 min respectively, 1 b/d, 1 week. Four control rats were kept at the Earth gravity (1G) in the room with the centrifuge. All animals were anaesthetized and anatomies 1 day after the last exposure. Ventricular myocardium was studied by electron microscopy and terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) method. The apoptosis of myocyte in control group and + 6Gz group were scarcely observed by electron microscopy, while heterochromatin concentration and margination were observed in + 10Gz group. The apoptotic index of myocardium increased significantly in + 6Gz and + 10Gz group compared with that of the control group (P < 0.05) and showed the largest value in the + 10Gz group (P < 0.05). Repeated + Gz exposures may induce apoptosis in myocyte, and the number of apoptosis in myocyte increases gradually with the increase of G value.


Zhang S.J.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2010

AIM: To examine the expression of IL-1beta, IL-1ra and IL-1R mRNA in the dentate gyrus of adult rats after lithium-pilocarpine (Li-PILO)-induced seizures. METHODS: Seizure epilepticus (SE) was induced using Li-PILO intraperitoneally (i.p.) injection. Lithium chloride was injected 18-20 h prior to PILO. The rats in the control group were given physiological saline instead of pilocarpine. We observed the behavior of rats and examined the expression of cytokines mRNA in dentate gyrus by RT-PCR. RESULTS: Rats had seizure epilepticus in 30 min after administrated of pilocarpine. Cytokines (IL-1beta, IL-1ra and IL-1R) began to increase significantly (P<0.05) at 1 h after SE, and the peak was at 6-12 h. Expression of all cytokines declined on 48 h after SE. CONCLUSION: Our findings suggested that SE lead to increased expression of IL-1, IL-1ra and IL-1R1 after lithium-pilocarpine-induced seizures, indicating that cytokines involved in SE and brain impairment after seizure.


Chen Y.R.,PLA Fourth Military Medical University
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2010

The aim of this study was to investigate the role of Delta-like 1 (Dll1) in differentiation and antigen pre-sensation of mouse bone marrow-derived dendritic cells (DCs). In the presence of granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin 4 (IL-4), mouse bone marrow cells were co-cultured with OP9-Dll1 and OP9-GFP cell lines respectively. After 8 days, the immature DCs were stimulated with tumor antigen. The surface molecules of the activated DCs including MHC II, CD80 and CD86 were analyzed by flow cytometry. Levels of IL-12 and IL-10 in the culture supernatant were detected by ELISA. In addition, the proliferation of T-cells co-cultured with DCs was analyzed by FACS through mixed T-lymphocyte reaction. The results showed that compared with OP9-GFP, the bone marrow cells co-cultured with OP9-Dll1 produced significantly more CD11c(+) DCs (p < 0.05), and possessed higher levels of surface molecule expression including MHC II, CD80 and CD86 after tumor antigen stimulation. The DCs secreted higher level of IL-12 (p < 0.05) and less IL-10 (p < 0.01). They also resulted in significantly stronger T-cell proliferation response. It is concluded that Dll1 can promote the differentiation of DCs from mouse bone marrow cells and enhance their antigen presentation capacity.


Dai X.,University of Sichuan | Wang H.,PLA Fourth Military Medical University | Jing Z.,University of Sichuan | Fu P.,University of Sichuan
Current Medical Research and Opinion | Year: 2014

Objective: As an ever widening array of anti-hyperglycemic agents are now available, the effect of these drugs on lipids is increasingly complex and controversial. The present meta-analysis was designed to clarify the effect of a dual combination of noninsulin anti-hyperglycemic agents on lipids in type 2 diabetes. Methods: Randomized controlled trials comparing different dual combinations of antidiabetic drugs were identified by searching PubMed, Cochrane Library, and Embase. Study selection, data abstraction and quality assessment were carried out by two reviewers independently. Change in low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride and total cholesterol were pooled by both traditional meta-analysis and network meta-analysis. Results: Eighteen studies with a total of 10,222 patients were included. Network meta-analysis suggested that metformin+dipeptidyl peptidase-4 inhibitors (DPP-4) (LDL cholesterol:-0.19mmol/L; HDL cholesterol: 0.06mmol/L; triglycerides:-0.73mmol/L; total cholesterol:-0.4mmol/L) and metformin+glucagon-like peptide-1 (GLP-1) agonist (LDL cholesterol:-0.3mmol/L; HDL cholesterol: 0.06mmol/L; triglycerides:-0.64mmol/L; total cholesterol:-0.5mmol/L) were associated with relatively larger beneficial effects on the lipid profile among all combinations. Compared with metformin+thiazolidinedione, metformin+GLP-1 agonist (mean difference:-0.38; 95% confidence interval [CI]:-0.66 to-0.10) significantly decreased LDL cholesterol. Metformin+thiazolidinedione showed a larger increase than metformin+sulfonylurea in HDL cholesterol (mean difference: 0.1; 95% CI: 0.01 to 0.21). Conclusions: The effect of a dual combination of noninsulin anti-hyperglycemic agents on lipids is moderate to small, with metformin+DPP-4 inhibitor and metformin+GLP-1 agonist showing consistent beneficial effects on LDL cholesterol, HDL cholesterol, triglycerides and total cholesterol. Future trials are needed to confirm these findings. © 2014 Informa UK Ltd.


Wang Y.,PLA Fourth Military Medical University
Cell biology international | Year: 2011

Ghrelin is thought to directly exert a protective effect on the cardiovascular system, specifically by promoting vascular endothelial cell function. Our study demonstrates the ability of ghrelin to promote rat CMEC (cardiac microvascular endothelial cell) proliferation, migration and NO (nitric oxide) secretion. CMECs were isolated from left ventricle of adult male Sprague-Dawley rat by enzyme digestion and maintained in endothelial cell medium. Dil-ac-LDL (1,1'-dioctadecyl-3,3,3',3'- tetramethylindocarbocyanine-labelled acetylated low-density lipoprotein) intake assays were used to identify CMECs. Cells were split into five groups and treated with varying concentrations of ghrelin as follows: one control non-treated group; three ghrelin dosage groups (1×10-9, 1×10-8, 1×10-7 mol/l) and one ghrelin+PI3K inhibitor group (1×10-7 mol/l ghrelin+20 μmol/l LY294002). After 24 h treatment, cell proliferation capability was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay and Western blot for PCNA (proliferating cell nuclear antigen) protein expression. Migration of CMECs was detected by transwell assays, and NO secretion of CMECs was measured via nitrate reduction. Protein expression of AKT and phosphorylated AKT in CMECs was measured by Western blot after exposure to various concentrations of ghrelin and the PI3K inhibitor LY294002. Our results indicate that ghrelin significantly enhanced cell growth at concentrations of 10-8 mol/l (0.271±0.041 compared with 0.199±0.021, P = 0.03) and 10-7 mol/l (0.296±0.039 compared with 0.199±0.021, P<0.01). However, addition of the PI3K/AKT inhibitor LY294002 inhibited the ghrelin-mediated enhancement in cell proliferation (0.227±0.042 compared with 0.199±0.021, P = 0.15). At a concentration between 10-8 and 10-7 mol/l, ghrelin caused a significant increase in the number of migrated cells compared with the control group (126±9 compared with 98±7, P = 0.02; 142±6 compared with 98±7, P<0.01), whereas no such change could be observed in the presence of 20 μmol/l of the PI3K/Akt inhibitor LY294002 (103±7 compared with 98±7, P = 0.32). Ghrelin treatment significantly enhanced NO production in a dose-dependent fashion compared with the untreated control group [(39.93±2.12) μmol/l compared with (30.27±2.71) μmol/l, P = 0.02; (56.80±1.98) μmol/l compared with (30.27±2.71) μmol/l, P<0.01]. However, pretreatment with 20 μmol/l LY294002 inhibited the ghrelin-stimulated increase in NO secretion [(28.97±1.64) μmol/l compared with (30.27±2.71) μmol/l, P = 0.37]. In summary, we have found that ghrelin treatment promotes the proliferation, migration and NO secretion of CMECs through activation of PI3K/AKT signalling pathway.


Imtiyaz H.Z.,University of Pennsylvania | Imtiyaz H.Z.,Howard Hughes Medical Institute | Williams E.P.,Howard Hughes Medical Institute | Williams E.P.,University of Pennsylvania | And 11 more authors.
Journal of Clinical Investigation | Year: 2010

Hypoxia-inducible factor 1α (HIF-1α) and HIF-2α display unique and sometimes opposing activities in regulating cellular energy homeostasis, cell fate decisions, and oncogenesis. Macrophages exposed to hypoxia accumulate both HIF-1α and HIF-2α, and overexpression of HIF-2α in tumor-associated macrophages (TAMs) is specifically correlated with high-grade human tumors and poor prognosis. However, the precise role of HIF-2α during macrophage-mediated inflammatory responses remains unclear. To fully characterize cellular hypoxic adaptations, distinct functions of HIF-1α versus HIF-2α must be elucidated. We demonstrate here that mice lacking HIF-2α in myeloid cells (Hif2aΔ/Δ mice) are resistant to lipopolysaccharide-induced endotoxemia and display a marked inability to mount inflammatory responses to cutaneous and peritoneal irritants. Furthermore, HIF-2α directly regulated proinflammatory cytokine/chemokine expression in macrophages activated in vitro. Hif2a Δ/Δ mice displayed reduced TAM infiltration in independent murine hepatocellular and colitisassociated colon carcinoma models, and this was associated with reduced tumor cell proliferation and progression. Notably, HIF-2α modulated macrophage migration by regulating the expression of the cytokine receptor M-CSFR and the chemokine receptor CXCR4, without altering intracellular ATP levels. Collectively, our data identify HIF-2α as an important regulator of innate immunity, suggesting it may be a useful therapeutic target for treating inflammatory disorders and cancer.


Li G.H.,PLA Fourth Military Medical University
Zhonghua zheng xing wai ke za zhi = Zhonghua zhengxing waike zazhi = Chinese journal of plastic surgery | Year: 2010

To evaluate the aesthetic effect of Millard' s method in patients with unilateral cleft lip by three dimensional sensing system. 19 patients with unilateral cleft lip (class II: 7 cases, class III: 12 cases) were randomly selected. The pre- and postoperative 3-D facial profiles were recorded using a 3 DSS scanner. Then 3D geometric models were established by Geomagic Studio 10.0. In the software, columella length, nostril floor width, alar base-subnasale distance, alar length, upper lip height, lateral upper lip height and lip length were measured before and after lip repair respectively. Paired-samples T test and one-sample T test were used for statistical analysis with SPSS 12. 0 software package. There were significant differences in the nostril floor width, alar base-subnasale distance, alar length and lip length before and after operation (P < 0.05, P < 0.01). The ratio of asymmetry in normal people was no more than 0.1. There was significant difference in the asymmetry ratio of columella length and lateral upper lip height between postoperative class II patients and normal people (P < 0.05). There was significant difference in the asymmetry ratio of columella length, nostril floor width, alar base-suhnasale distance, lateral upper lip height and lip length between postoperative class III patients and normal people (P < 0.05 or P < 0.01). Millard's technique is useful for repairing unilateral cleft lip in rebuilding nasal floor, the Cupid' bow and in correction of the columella deviation, except for a relatively insufficient lip height and columella length at the operated side. Besides, the nostril floor width at the operated side in class III patients is still wider than that at the opposite side.


Bai Y.,Albany Medical College | Bai Y.,PLA Fourth Military Medical University | Yang J.,Albany Medical College | Eisele L.E.,New York State Department of Health | And 5 more authors.
Journal of Bacteriology | Year: 2013

Cyclic di-AMP (c-di-AMP) and cyclic di-GMP (c-di-GMP) are signaling molecules that play important roles in bacterial biology and pathogenesis. However, these nucleotides have not been explored in Streptococcus pneumoniae, an important bacterial pathogen. In this study, we characterized the c-di-AMP-associated genes of S. pneumoniae. The results showed that SPD_1392 (DacA) is a diadenylate cyclase that converts ATP to c-di-AMP. Both SPD_2032 (Pde1) and SPD_1153 (Pde2), which belong to the DHH subfamily 1 proteins, displayed c-di-AMP phosphodiesterase activity. Pde1 cleaved c-di-AMP into phosphoadenylyl adenosine (pApA), whereas Pde2 directly hydrolyzed c-di-AMP into AMP. Additionally, Pde2, but not Pde1, degraded pApA into AMP. Our results also demonstrated that both Pde1 and Pde2 played roles in bacterial growth, resistance to UV treatment, and virulence in a mouse pneumonia model. These results indicate that c-di-AMP homeostasis is essential for pneumococcal biology and disease. © 2013, American Society for Microbiology.


Li F.,PLA Fourth Military Medical University | Li F.,University of Maryland, Baltimore | Weir M.D.,University of Maryland, Baltimore | Fouad A.F.,University of Maryland, Baltimore | And 2 more authors.
Journal of Dentistry | Year: 2013

Objectives The objectives of this study were to investigate: (1) the antibacterial activity of two antibacterial monomers, dimethylaminododecyl methacrylate (DMADDM) and dimethylammoniumethyl dimethacrylate (DMAEDM), against eight different species of oral pathogens for the first time; (2) the cytotoxicity of DMAEDM and DMADDM. Methods DMAEDM and DMADDM were synthesized by reacting a tertiary amine group with an organo-halide. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against eight species of bacteria were tested. Time-kill determinations were performed to examine the bactericidal kinetics. Cytotoxicity of monomers on human gingival fibroblasts (HGF) was assessed using a methyl thiazolyltetrazolium assay and live/dead viability assay. Results DMADDM showed strong bactericidal activity against all bacteria, with MIC of 1.2-9.8 μg/mL. DMAEDM had MIC of 20-80 mg/mL. Time-kill determinations indicated that DMADDM and DMAEDM had rapid killing effects against eight species of bacteria, and eliminated all bacteria in 30 min at the concentration of 4-fold MBC. Median lethal concentration for DMADDM and DMAEDM was between 20 and 40 μg/mL, which was 20-fold higher than 1-2 μg/mL for BisGMA control. Conclusions DMAEDM and DMADDM were tested in time-kill assay against eight species of oral bacteria for the first time. Both were effective in bacteria-inhibition, but DMADDM had a higher potency than DMAEDM. Different killing efficacy was found against different bacteria species. DMAEDM and DMADDM had much lower cytotoxicity than BisGMA. Therefore, DMADDM and DMAEDM are promising for use in bonding agents and other restorative/preventive materials to combat a variety of oral pathogens.


Zhu H.,State University of New York at Stony Brook | Fan Y.,State University of New York at Stony Brook | Lu H.,PLA Fourth Military Medical University | Liang Z.,State University of New York at Stony Brook
Academic Radiology | Year: 2011

Rationale and Objectives: Current schemes for computer-aided detection (CAD) of colon polyps usually use kernel methods to perform curvature-based shape analysis. However, kernel methods may deliver spurious curvature estimations if the kernel contains two surfaces, because of the vanished gradient magnitudes. The aim of this study was to use the Knutsson mapping method to deal with the difficulty of providing better curvature estimations and to assess the impact of improved curvature estimation on the performance of CAD schemes. Materials and Methods: The new method was compared to two widely used kernel methods in terms of the performance of two stages of CAD: initial detection and true-positive and false-positive classification. The evaluation was conducted on a database of 130 computed tomographic scans from 67 patients. In these patient scans, there were 104 clinically significant polyps and masses >5 mm. Results: In the initial detection stage, the detection sensitivity of the three methods was comparable. In the classification stage, at a 90% sensitivity level on the basis of the input of this step, the new technique yielded 3.15 false-positive results per scan, demonstrating reductions in false-positive findings of 30.2% (P < .01) and 27.9% (P < .01) compared to the two kernel methods. Conclusions: The new method can benefit CAD schemes with reduced false-positive rates, without sacrificing detection sensitivity. © 2011 AUR.


Zhang R.,Shaanxi Normal University | Zhao Y.,PLA Fourth Military Medical University | Sun Y.,Shaanxi Normal University | Lu X.,Shaanxi Normal University | Yang X.,Shaanxi Normal University
Journal of Agricultural and Food Chemistry | Year: 2013

This study was aimed to isolate and characterize the raffinose family oligosaccharides (RGOs) from a novel plant source of Rehmannia glutinosa Libosch, and further evaluate whether RGOs can attenuate CCl4-induced oxidative stress and hepatopathy in mice. HPLC analysis showed that RGOs were mainly composed of stachyose (61.7%, w/w), followed by 23.7% raffinose and 7.1% sucrose. Administration of RGOs orally daily in mice for 21 days significantly reduced the impact of CCl4 toxicity on the serum markers of liver damage, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total-cholesterol (TC), and triglycerides (TG). RGOs also increased antioxidant levels of hepatic glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), and ameliorated the elevated hepatic formation of malonaldehyde (MDA) induced by CCl4 in mice, which coincided with the histological alteration. These findings exhibited the potential prospect of RGOs as functional ingredients to prevent ROS-related liver damage. © 2013 American Chemical Society.


Guo T.,PLA Fourth Military Medical University
Shanghai kou qiang yi xue = Shanghai journal of stomatology | Year: 2013

As an editor of dental journals, the author found that some inappropriate writing and mistakes existed in many articles, which reduced the quality of the published papers. The problems can be divided into three categories: irregular terminology; not concise, inaccurate description; improper use of punctuation and title code. They were illustrated respectively in this article for readers to avoid these mistakes in the future.


Zhou H.,University of Sichuan | Zhou H.,University of Maryland, Baltimore | Li F.,University of Maryland, Baltimore | Li F.,PLA Fourth Military Medical University | And 3 more authors.
Journal of Dentistry | Year: 2013

Objectives Antibacterial bonding agents are promising to combat bacteria and caries at tooth-restoration margins. The objectives of this study were to incorporate new quaternary ammonium methacrylates (QAMs) to bonding agent and determine the effects of alkyl chain length (CL) and quaternary amine charge density on dental plaque microcosm bacteria response for the first time. Methods Six QAMs were synthesized with CL = 3, 6, 9, 12, 16, 18. Each QAM was incorporated into Scotchbond multi-purpose (SBMP). To determine the charge density effect, dimethylaminododecyl methacrylate (DMAHDM, CL = 16) was mixed into SBMP at mass fraction = 0%, 2.5%, 5%, 7.5%, 10%. Charge density was measured using a fluorescein dye method. Dental plaque microcosm using saliva from ten donors was tested. Bacteria were inoculated on resins. Early-attachment was tested at 4 h. Biofilm colony-forming units (CFU) were measured at 2 days. Results Incorporating QAMs into SBMP reduced bacteria early-attachment. Microcosm biofilm CFU for CL = 16 was 4 log lower than SBMP control. Charge density of bonding agent increased with DMAHDM content. Bacteria early-attachment decreased with increasing charge density. Biofilm CFU at 10% DMAHDM was reduced by 4 log. The killing effect was similarly-strong against total microorganisms, total streptococci, and mutans streptococci. Conclusions Increasing alkyl chain length and charge density of bonding agent was shown for the first time to decrease microcosm bacteria attachment and reduce biofilm CFU by 4 orders of magnitude. Novel antibacterial resins with tailored chain length and charge density are promising for wide applications in bonding, cements, sealants and composites to inhibit biofilms and caries. © 2013 Elsevier Ltd.


Yang M.,Institute of Orthopaedics and Traumatology of PLA of China | Yan M.,Institute of Orthopaedics and Traumatology of PLA of China | Zhang R.,PLA Fourth Military Medical University | Li J.,Institute of Orthopaedics and Traumatology of PLA of China | Luo Z.,Institute of Orthopaedics and Traumatology of PLA of China
Cancer Science | Year: 2011

It has been proven that "side population (SP)" cells that exclude Hoechst 33342 dye are enriched with cancer stem cells in several tumors. In the present study we aimed to isolate and characterize SP cells from human primary osteosarcoma. Side population cells were detected in osteosarcoma samples. In vitro, SP cells regenerated both SP and non-SP and the clonogenicity of SP cells was higher than that of non-SP cells, just like stem cells. In vivo, SP cells exhibited heightened tumorigenicity and only the SP fraction had the capacity to self- renew both in vitro and in vivo. Furthermore, SP cells exhibited increased multidrug resistance and the RNA expression of ATP-binding cassette protein transporters was increased in the SP group. In addition, "stemness" genes Oct-4 and Nanog were also upregulated in the SP group. However, the expression of other putative stem cell markers (CD44, CD117 and CD133) had no significant difference between SP and non-SP for each individual marker. These findings suggest that SP cells derived from osteosarcoma are enriched with tumorigenic cells with stem-like properties and might be an ideal target for clinical therapy. © 2011 Japanese Cancer Association.


The efficacy of ursodeoxycholic acid (UDCA) on long-term outcome of primary biliary cirrhosis (PBC) has been less documented in Chinese cohort. We aimed to assess the therapeutic effect of UDCA on Chinese patients with PBC. In the present study, 67 patients with PBC were treated with UDCA (13-15 mg·kg(-1)·day(-1)) and followed up for 2 years to evaluate the changes of symptoms, laboratory values and histological features. As the results indicated, fatigue and pruritus were obviously improved by UDCA, particularly in patients with mild or moderate symptoms. The alkaline phosphatase and γ-glutamyl transpetidase levels significantly declined at year 2 comparing to baseline values, with the most profound effects achieved in patients at stage 2. The levels of alanine aminotransferase and aspartate aminotransferase significantly decreased whereas serum bilirubin and immunoglobulin M levels exhibited no significant change. Histological feature was stable in patients at stages 1-2 but still progressed in patients at stages 3-4. The biochemical response of patients at stage 2 was much better than that of patients at stages 3-4. These data suggest that, when treated in earlier stage, patients in long-term administration of UDCA can gain favorable results not only on symptoms and biochemical responses but also on histology. It is also indicated that later histological stage, bad biochemical response and severe symptom may be indicators of poor prognosis for UDCA therapy.


Zhang J.,University of Houston | Zhang J.,PLA Fourth Military Medical University | Chang D.Y.,University of Houston | Mercado-Uribe I.,University of Houston | Liu J.,University of Houston
Human Pathology | Year: 2012

Sex-determining region Y-box 2 is proposed to be a key transcription factor in embryonic stem cells. The known roles of sex-determining region Y-box 2 in development and cell differentiation suggest that it is relevant to the aberrant growth of tumor cells. Thus, sex-determining region Y-box 2 may play an important role in tumor progression. However, its clinical significance in human ovarian carcinoma has been uncertain until recently. The aim of the present study was to clarify the clinical role of sex-determining region Y-box 2 expression in ovarian carcinoma. Immunohistochemical staining of 540 human ovarian carcinoma samples for sex-determining region Y-box 2 was performed using tissue microarray. The associations among sex-determining region Y-box 2 expression and clinical factors (diagnosis, tumor grade, International Federation of Gynecology and Obstetrics stage, and response to chemotherapy), overall survival, and disease-free survival were analyzed. We observed sex-determining region Y-box 2 expression in 15% of the ovarian carcinoma samples. Use of the Fisher exact test suggested that sex-determining region Y-box 2 expression was associated with high-grade carcinoma (P =.009), especially high-grade serous carcinoma (P =.048); International Federation of Gynecology and Obstetrics stage (II-IV; P =.005); and malignant mixed müllerian tumors (P =.048). Sex-determining region Y-box 2 expression was also associated with decreased disease-free survival durations (P =.035; log-rank test). Our results showed that sex-determining region Y-box 2 expression may be a potential marker related to tumor recurrence, as implicated by its role in cancer stem cells. © 2012 Elsevier Inc. All rights reserved.


Tian L.,Shaanxi Normal University | Zhao Y.,PLA Fourth Military Medical University | Guo C.,Shaanxi Normal University | Yang X.,Shaanxi Normal University
Carbohydrate Polymers | Year: 2011

This study is designed to compare the antioxidant potential of a water-soluble polysaccharide (HCP) with solvent extracts (water, ethanol, ethyl acetate and chloroform) from Houttuynia cordata Thunb. The results showed that polar water extract exhibited the highest reducing power and scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, superoxide radical and hydroxyl radical, which were correlated with its high level of biopolymer HCP. Furthermore, the active HCP was identified as an acid hetero-polysaccharide by a rapid HPLC technology within 20 min, and galacturonic acid (29.4%) and galactose (24.0%) were approved as the prominent components of HCP, followed by rhamnose (17.2%), arabinose (13.5%), glucuronic acid (6.8%), glucose (5.3%), xylose (2.1%) and mannose (1.8%) in the molar percentages. This finding suggests that HCP is one of the main active ingredients responsible for antioxidant effect of H. cordata, which might be valuable as a natural antioxidant source applied in both healthy medicine and food industry. © 2010 Elsevier Ltd. All rights reserved.


Wang Y.,PLA Fourth Military Medical University | Wang Y.,Tulane University | Zheng Y.,Fujian Medical University | Zheng Y.,Tulane University | And 2 more authors.
Developmental Biology | Year: 2013

Meckel's cartilage is a transient supporting tissue of the embryonic mandible in mammals, and disappears by taking different ultimate cell fate along the distal-proximal axis, with the majority (middle portion) undergoing degeneration and chondroclastic resorption. While a number of factors have been implicated in the degeneration and resorption processes, signaling pathways that trigger this degradation are currently unknown. BMP signaling has been implicated in almost every step of chondrogenesis. In this study, we used Noggin mutant mice as a model for gain-of-BMP signaling function to investigate the function of BMP signaling in Meckel's cartilage development, with a focus on the middle portion. We showed that Bmp2 and Bmp7 are expressed in early developing Meckels' cartilage, but their expression disappears thereafter. In contrast, Noggin is expressed constantly in Meckel's cartilage throughout the entire gestation period. In the absence of Noggin, Meckel's cartilage is significantly thickened attributing to dramatically elevated cell proliferation rate associated with enhanced phosphorylated Smad1/5/8 expression. Interestingly, instead of taking a degeneration fate, the middle portion of Meckel's cartilage in Noggin mutants undergoes chondrogenic differentiation and endochondral ossification contributing to the forming mandible. Chondrocyte-specific expression of a constitutively active form of BMPRIa but not BMPRIb leads to enlargement of Meckel's cartilage, phenocopying the consequence of Noggin deficiency. Our results demonstrate that elevated BMP signaling prevents degeneration and leads to endochondral ossification of Meckel's cartilage, and support the idea that withdrawal of BMP signaling is required for normal Meckel's cartilage development and ultimate cell fate. © 2013 Elsevier Inc.


Tang Y.,Xian University of Science and Technology | Mi C.,Shaanxi Normal University | Mi C.,Xian University of Science and Technology | Liu J.,Xian University of Science and Technology | And 2 more authors.
Cardiovascular Pathology | Year: 2014

Background Hypertension leads to cardiac hypertrophy as an adaptive response to increased workload. While initial development of hypertrophy is compensatory when contractile function is maintained, persistent stress on heart leads to deteriorated cardiac function and onset of heart failure. Mitochondrial dysfunction develops in the failing heart; however, whether it presents in compensatory cardiac hypertrophy is controversial. Methods Spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar Kyoto rats were used in the study. Mitochondrial function and remodeling-related mechanisms in the left ventricles were measured by enzyme activity tests, Western blots, and reverse transcriptase polymerase chain reaction. Results Compensatory cardiac hypertrophy in SHR was indicated by higher heart/weigh ratio, left ventricular systolic pressure and ±dp/dtmax (P<.001, P<.05, and P<.01, respectively). Enzyme activities of mitochondrial complex I and II were significantly reduced (P<.05 and P<.01) in SHR in concert with decreased expression of complex subunits (P<.01 for NDUFS3, P=.068 for SDHB, and P<.05 for ATP5A1). Mitochondrial fission protein Drp1 was decreased (P<.05), while fusion protein OPA1 was increased (P<.01). Parkin and SirT1/AMPK-PGC-1α signaling, responsible for mitochondrial elimination and biogenesis respectively, were decreased in SHR (P<.01 for Parkin, P<.001 for SirT1 and p-AMPK). Conclusion Our results implicated that mitochondrial function and remodeling, indicated by mitochondrial enzyme activities and remodeling-related molecules, were compromised in compensatory hypertrophied myocardium of the SHR hypertensive model. Summary Mitochondrial function in compensatory hypertrophied myocardium is controversial. Our present study found mitochondrial dysfunction in the left ventricle of spontaneously hypertensive rats, which was possibly a result of compromised mitochondrial remodeling including mitochondrial dynamics, elimination, and biogenesis. © 2014 Elsevier Inc.


Li X.,Samuel Oschin Comprehensive Cancer Institute | Chen Y.-T.,Samuel Oschin Comprehensive Cancer Institute | Hu P.,Samuel Oschin Comprehensive Cancer Institute | Hu P.,PLA Fourth Military Medical University | Huang W.-C.,Samuel Oschin Comprehensive Cancer Institute
Molecular Cancer Therapeutics | Year: 2014

Current research links aberrant lipogenesis and cholesterogenesis with prostate cancer development and progression. Sterol regulatory element-binding proteins (SREBP; SREBP-1 and SREBP-2) are key transcription factors controlling lipogenesis and cholesterogenesis via the regulation of genes related to fatty acid and cholesterol biosynthesis. Overexpression of SREBPs has been reported to be significantly associated with aggressive pathologic features in human prostate cancer. Our previous results showed that SREBP-1 promoted prostate cancer growth and castration resistance through induction of lipogenesis and androgen receptor (AR) activity. In the present study, we evaluated the anti-prostate tumor activity of a novel SREBP inhibitor, fatostatin.Wefound that fatostatin suppressed cell proliferation and anchorage-independent colony formation in both androgen-responsive LNCaP and androgen-insensitive C4-2B prostate cancer cells. Fatostatin also reduced in vitro invasion and migration in both the cell lines. Further, fatostatin caused G2-M cell-cycle arrest and induced apoptosis by increasing caspase-3/7 activity and the cleavages of caspase-3 and PARP. The in vivo animal results demonstrated that fatostatin significantly inhibited subcutaneous C4-2B tumor growth and markedly decreased serum prostate-specific antigen (PSA) level compared with the control group. The in vitro and in vivo effects of fatostatin treatment were due to blockade of SREBP-regulated metabolic pathways and the AR signaling network. Our findings identify SREBP inhibition as a potential new therapeutic approach for the treatment of prostate cancer. Mol Cancer Ther; 13(4); 855-66. © 2014 AACR.


Liang R.,PLA Fourth Military Medical University
Journal of Leukemia and Lymphoma | Year: 2013

Objective To improve the understanding of clinical and pathological features of extranodal NK/T cell lymphoma, nasal type (NKTL) with poor prognosis and provide experiential references via a retrospective analysis. Methods 117 NKTL cases in a single center were retrospectively analyzed of their pathologic diagnoses and clinical manifestations, especially primary sites. Pathological examinations were mainly depended on morphology, immunohistochemisty for immunophenotype, and in situ hybridization for Epstein-Barr virus (EBV) encoded small RNA (EBER). Polymerase chain reaction (PCR) for whole-blood EBV DNA and T-cell receptor (TCR) gene rearrangement was performed. Chemotherapy and radiotherapy were the main treatments. International prognostic index, Ki-67, 2 years overall survival (OS) rate and progressive free survival (PFS) rate according to the clinical characteristics were included in the univariable analysis. Results The positive rate for CD3 was 90.6 %, 94.0 % for CD56, 92.9 % for CD45RO, 97.9 % for TIA, 97.7 % for Granzyme B and 100.0 % for EBER, respectively. The median age was 43.2 (14-77) years old. The primary nasal NKTL was 95 cases (81.2 %) and their average Ki-67 was (48.3±2.6) %. Other primary extranodal NKTL was 22 cases (18.8 %), including primary posterior pharyngeal wall, tongue, tonsil, laryngeal, lymph nodes, skin, liver, intestinal, central nervous system and testis. Patients with primary liver or intestinal NKTL or Ki-67 greater than 80 % died in the first year. Patients with primary liver and intestinal NKTL had higher Ki-67 than patients with primary nasal. Compared to the 2 years OS rate 60.0 % and PFS rate 36.0 % of patients with Ki-67 from 60 % to 80 %, the OS rate (86.3 %) and PFS rate (57.5 %) of patients with Ki-67 from 30 % to 60 % were higher (P = 0.047,0.070), and the OS rate (100.0 %) and PFS rate (78.0 %) of patients with Ki-67 less than 30 % were also higher (P = 0.01, 0.02). 2 years OS rate of 8 CD56 negative patients whose T cell rearrangement was positive and primary sites were nasal was higher than that of 109 CD56 positive patients (P = 0.03, 0.02). Among the 13 EBV DNA samples detected, 8 samples were normal and OS rate was 100.0 %. 5 samples had more than 6.1x107 copies/ml and OS rate was 60.0 %. Conclusion It is implied that Ki-67, CD56, EBER, EBV-DNA and primary site are related with the prognosis of NKTL.


Ma X.,Xian Jiaotong University | Wang Y.,PLA Fourth Military Medical University | Guo H.,Changzhou Institute of Technology | Wang J.,Xian Jiaotong University
Journal of Bioactive and Compatible Polymers | Year: 2011

A three-dimensional porous nano-hydroxyapatite (nHA)/chitosan (CS) biocomposite was synthesized. The rod-like nHA grains of 15-30 × 5-10 nm in size were observed by TEM and confirmed by characteristic XRD patterns. The diameters of the interconnecting pores of the nHA/CS biocomposite, determined by SEM, were 120-300 μm. Standard critical-sized calvarial bone defect ( Ø = 6.5 mm) was created in Sprague-Dawley (SD) rats. In group 1, nHA/CS was implanted and in group 2, no implant was made in the defect. After 1 week, the histological assessment of group 1 clearly showed that a large number of living cells were anchored in the pores of the nHA/CS implants. New bone formation, both at the edge and in the center of implants, was found as early as 2 weeks. Histological assays confirmed that the newly formed bone tissue was bioactive and neovascularized. After 5 weeks, the mineral content and volume of the newly formed bone tissue in the defects were significantly greater in group 1 than in group 2 (p < 0.01). These results indicate that implantation of the nHA/CS enhanced the repair of bone defect and confirm the potential of this biocomposite as a bioactive bone grafting substitute. © 2011 The Author(s).


Ren D.,Shaanxi Normal University | Zhao Y.,PLA Fourth Military Medical University | Nie Y.,Shaanxi Normal University | Yang N.,Shaanxi Normal University | Yang X.,Shaanxi Normal University
International Journal of Biological Macromolecules | Year: 2014

Intake of dietary high fructose (HF) exerts a number of adverse metabolic effects. The present study was to investigate whether Artemisia sphaerocephala Krasch seed polysaccharides (ASKP) alleviated hyperglycemia, hepatic steatosis and oxidative injury in mice fed HF water. After 8 weeks of the experiment, administration of ASKP at 400 and 800. mg/kg. bw significantly reduced the fasting serum glucose, insulin concentrations and the homeostasis model assessment of basal insulin resistance (HOMA-IR) of the mice fed 20% HF water. In the oral glucose tolerance test, the administration of ASKP at 400 and 800. mg/kg. bw had a reduced plasma glucose concentrations after 15. min of glucose loading in HF-fed mice, indicating that ASKP improved glucose intolerance. ASKP also remarkably ameliorated the HF-induced elevation of liver lipid contents and oxidative injury in mice, and caused the reduction of liver lipid peroxidation and the elevation of hepatic antioxidant system. Histopathology of the liver by conventional H&E and Oil Red O staining confirmed the liver steatosis and oxidative injury induced by HF diet and the hepatoprotective effect of ASKP. This is the first report showing that ASKP can ameliorate the high fructose-induced hyperglycemia, hepatic steatosis and oxidative injury. © 2014 Elsevier B.V.


Zhao Y.,PLA Fourth Military Medical University
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2013

To learn the anatomical structure of the parapharyngeal space and to analyze the pathological type, preoperative evaluation and choice of surgical approach of parapharyngeal space tumors. To conduct a retrospective analysis of the clinical data of 43 patients who receive surgery in our department from March 2002 to January 2011. All patients undergo enhanced CT and MRI before surgery and enhanced CT reconstruction was also adopted in the cases after the year 2009. All 43 cases of surgeries were performed under general anesthesia. Of all the cases, the lateral neck path were chosen for 38 cases, lateral neck parotid path for 3 and lateral neck path combined with mandibular split operation for 2, 1 of which tracheotomy was conducted. Suction drainage was placed in the surgical cavity of all cases. And patients without contraindications were treated with glucocorticoids. In 42 of all 43 cases, the tumor was removed completely during the first operation while tumor reoccurred after 3 years and was cured by reoperation in the other one case. Parapharyngeal space is deep and the anatomy structure is complicated. Cancer incidence rate is low and mostly benign in this regional. Surgical resection is the preferred treatment and lateral neck approach is most commonly used. CT and MRI is an effective preoperative examination and enhanced CT reconstruction can provide a more intuitive spatial conformation.


Zhang X.G.,PLA Fourth Military Medical University
Sheng li ke xue jin zhan [Progress in physiology] | Year: 2011

The antimicrobial peptide is a class of small molecule peptide derived from a variety of creatures, able to kill the pathogens efficiently and has the potential of broad-spectrum activity, rapid and strong bactericidal activity, low propensity for resistance development, and many other advantages. As a new generation of anti-infective drug candidates, the mechanism of antimicrobial peptides has not yet entirely clear, but now there are two views have been widely recognized that the destruction of permeation through the membrane structural integrity and through the different intracellular target to affect bacterium growth and metabolic balance. In this paper, the physical and chemical properties, secondary structure, mechanism, and the relationship between the latter two to make a conclusion, in order to better understand the structure-activity relationships and to provide a theoretical basis for rational design of antimicrobial peptides.


Ji G.,Texas Tech University Health Sciences Center | Li Z.,PLA Fourth Military Medical University | Neugebauer V.,Texas Tech University Health Sciences Center
Pain | Year: 2015

Accumulating evidence suggests an important contribution of reactive oxygen species (ROS) to pain and neuropsychiatric disorders, but their role in pain-related plasticity in the brain is largely unknown. Neuroplasticity in the central nucleus of the amygdala (CeA) correlates positively with pain behaviors in different models. Little is known, however, about mechanisms of visceral pain-related amygdala changes. The electrophysiological and behavioral studies reported here addressed the role of ROS in the CeA in a visceral pain model induced by intracolonic zymosan. Vocalizations to colorectal distension and anxiety-like behavior increased after intracolonic zymosan and were inhibited by intra-CeA application of a ROS scavenger (tempol, a superoxide dismutase mimetic). Tempol also induced a place preference in zymosan-treated rats but not in controls. Single-unit recordings of CeA neurons in anesthetized rats showed increases of background activity and responses to visceral stimuli after intracolonic zymosan. Intra-CeA application of tempol inhibited the increased activity but had no effect under normal conditions. Whole-cell patch-clamp recordings of CeA neurons in brain slices from zymosan-treated rats showed that tempol decreased neuronal excitability and excitatory synaptic transmission of presumed nociceptive inputs from the brainstem (parabrachial area) through a combination of presynaptic and postsynaptic actions. Tempol had no effect in brain slices from sham controls. The results suggest that ROS contribute to visceral pain-related hyperactivity of amygdala neurons and amygdala-dependent behaviors through a mechanism that involves increased excitatory transmission and excitability of CeA neurons. © 2015 International Association for the Study of Pain.


To study the extent and severity of macrovasculopathy in systemic sclerosis (SSc; scleroderma) patients by comparing both local and regional arterial stiffness parameters. The local arterial stiffness indices of the right common carotid artery, right brachial artery, right radial artery, right superficial femoral artery, and right posterior tibial artery were measured in 25 SSc patients and strictly matched healthy controls. The regional pulse wave velocity (PWV) of each arterial segment was also calculated from wave intensity analysis. There were no differences between the two groups in the stiffness index (β), Peterson's pressure modulus, arterial compliance, and local PWV derived from β (PWVβ) of all vessels except the right brachial artery, of which β, Peterson's pressure modulus, and PWVβ were markedly lower and arterial compliance was higher in SSc patients compared with controls (P<0.05). The forearm (brachial-radial) and arm (carotid-radial) PWVs were significantly higher in SSc patients than in controls (mean±SD 12.1±7.1 meters/second versus 8.3±3.5 meters/second and mean±SD 7.9±1.9 meters/second versus 6.9±1.5 meters/second, respectively; P<0.05), whereas the upper arm (carotid-brachial), aortic (carotid-femoral), and leg (femoral-ankle) PWVs were not different between groups. The aortic PWV was also higher in the diffuse cutaneous SSc subgroup than in controls (mean 6.2, 95% confidence interval [95% CI] 5.4-6.9 meters/second versus mean 5.1, 95% CI 4.7-5.6 meters/second; P<0.05) after adjusting for potentially influential variables. The macrovasculopathy occurs preferentially at the forearm and aorta in SSc, which can be sensitively and reliably detected by regional PWVs rather than commonly used local arterial stiffness indices. Copyright © 2011 by the American College of Rheumatology.


Ma Z.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2013

To detect cell frequency and surface markers of peripheral blood CD4+;CXCR5+;follicular helper T cells (Tfh cells) and analyze the correlation between CD4+;CXCR5+;Tfh cells and hyperglobulinemia of patients with chronic hepatitis B. We collected blood samples of 20 HBV infected patients with hyperglobulinemia, 10 chronic HBV infected patients and 10 health volunteers and isolated plasma and peripheral blood mononuclear cells (PBMCs). The percentage of CD4+;CXCR5+;Tfh cells and the expressions of PD-1, ICOS and CD40L on CD4+;CXCR5+;Tfh cells were detected by flow cytometry. The levels of CXCL13, IFN-γ and IL-21 in plasma were measured by ELISA. Compared with the percentage of CD4+;CXCR5+;Tfh cells in chronic HBV infected patients (11.9 ± 3.9) and health controls (6.8 ± 3.9), it was higher in HBV infected patients with hyperglobulinemia (22.6 ± 4.7, P<0.05). And in the hyperglobulinemia patients, the expressions of PD-1 and CD40L on CD4+;CXCR5+;Tfh cells and the levels of CXCL13 and IL-21 in plasma increased, whereas the level of IFN-γ significantly declined (P<0.05). The results suggest that CD4+;CXCR5+;Tfh cells may participate in the pathogenesis of hyperglobulinemia during HBV infection.


DU J.J.,PLA Fourth Military Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2011

To evaluate the safety and feasibility of hand-sewn anastomosis in totally laparoscopic colectomy. Clinical data of 19 consecutive patients with benign(n=5) or malignant colonic diseases(n=14, 4 ascending colon cancers, 2 transverse colon cancers, and 8 sigmoid colon cancers) treated with totally laparoscopic colectomy with a hand-sewn anastomosis were reviewed. All the procedures were performed by the same surgeon team including totally laparoscopic resection and hand-sewn anastomosis, ileocolic anastomosis after right hemicolectomy, and hand-sewn purse-string sutures in the colon. Hand-sewn anastomosis was performed for 11 patients and circular-stapled anastomosis with hand-sewn purse-string sutures was performed for other 8 patients. The mean hand-sewn anastomosis time was (49.5 ± 29.4) min, and the mean hand-sewn purse-string sutures time was (13.3 ± 5.5) min. No patients required conversion to laparoscopy-assisted or open surgery, and there were no postoperative complications related to anastomosis. One patient with transverse colon lipoma developed mild intra-abdominal infection after surgery and recovered after conservative treatment. Totally laparoscopic intracorporeal hand-sewn anastomosis or hand-sewn purse-string sutures for colectomy is feasible and safe when performed by experienced laparoscopic surgeons.


Wang J.-W.,Peoples Hospital of Zhengzhou | Tang C.,Xian Electricity Hospital | Pan B.-R.,PLA Fourth Military Medical University
International Journal of Ophthalmology | Year: 2012

AIM: To explore the optim al low dose of MSCT in orbital trauma examination. METHODS: Sixty transv erse images of the fracture layer were selected. Low-dose images acquired at 30, 70, 100, 140, 170, and 200 milliam pere (mA) were simulated by adding noise to the image space using software. After assessing the images according to the conditions of image quality and fracture, we found the optimal tube current that met diagnostic requirements and then applied it to clinical use. The CT Dose Index volume (CTDIvol), dose length product (DLP) and effective dose (ED) were recorded. The image quality was classified as good, fairly good, ordinary, poor, or very poor according to image level, noise, anatomic structure and whether the diagnostic requirem ents were met or not. The rank-sum test was used to perform statistical analysis on the ranked data. The Chi-square test was used for the num erical data. RESULTS: Under the scan conditions of a conv entional dose of 300mA, 60 cases of orbital fracture, 38 cases of orbital em phy sem a, 25 cases of ocular dam age, and 3 cases of intraorbital foreign body were dem onstrated in the images of the 60 orbital traum a patients. Among the low dose simulated images, the image quality difference of the different doses was of statistical significance (χ2=15.678, P=0.016). When the dose was lowered to 70mA, the above mentioned clinical signs were still clear and diagnostic, however the image quality assessment results indicated that 2 cases were good, 16 cases were fairly good, and 42 cases were ordinary, poor or very poor. When the simulated dose tube current was 100m A, the image quality assessment results were 18 cases good, 34 cases fairly good, and 8 cases ordinary, poor and very poor; compared with the conventional dose, there was no statistical significance (P>0.05). When using a 100m A tube current to examine 40 cases of orbital traum a patients in the clinic, the acquired image quality was 10 cases good, 26 cases fairly good and 4 cases ordinary, without any cases of poor or very poor. The CTDIvol, DLP and ED were 20.72m Gy, 124.97 mGy·cm and 0.26m Sv, respectively, while the CTDIvol, DLP and ED were 62.53m Gy, 375.18 mGy·GTtl and 0.86m Sv, respectively, when using a conv entional dose of 300m A. Compared with the tube current of 100m A for scanning, the ED declined 70%. CONCLUSION: When conducting an MSCT scan for orbital trauma, the acquired images using the 100m A tube current can meet the clinical diagnostic requirements, and the radiation dose to the patients can be decreased. Copyright International Journal of Ophthalmology Press.


Cellular plasticity has an important role in the progression of hepatocellular carcinoma (HCC). In this study, the involvement of a TGF-β1-CD147 self-sustaining network in the regulation of the dedifferentiation progress was fully explored in HCC cell lines, hepatocyte-specific basigin/CD147-knockout mice and human HCC tissues. We demonstrated that TGF-β1 stimulation upregulated CD147 expression and mediated the dedifferentiation of HCC cells, whereas all-trans-retinoic acid induced the downregulation of CD147 and promoted differentiation in HCC cells. Overexpression of CD147 induced the dedifferentiation and enhanced the malignancy of HCC cells, and increased the transcriptional expression of TGF-β1 by activating β-catenin. CD147-induced matrix metalloproteinase (MMP) production activated pro-TGF-β1. The activated TGF-β1 signaling subsequently repressed the HNF4α expression via Smad-Snail1 signaling and enhanced the dedifferentiation progress. Hepatocyte-specific basigin/CD147-knockout mice decreased the susceptibility to N-nitrosodiethylamine-induced tumorigenesis by suppressing TGF-β1-CD147 signaling and inhibiting dedifferentiation in hepatocytes during tumor progression. CD147 was positively correlated with TGF-β1 and negatively correlated with HNF4α in human HCC tissues. Positive CD147 staining and lower HNF4α levels in tumor tissues were significantly associated with poor survival of patients with HCC. The overexpression of HNF4α and Smad7 and the deletion of CD147 by lentiviral vectors jointly reprogrammed the expression profile of hepatocyte markers and attenuated malignant properties including proliferation, cell survival and tumor growth of HCC cells. Our results highlight the important role of the TGF-β1-CD147 self-sustaining network in driving HCC development by regulating differentiation plasticity, which provides a strong basis for further investigations of the differentiation therapy of HCC targeting TGF-β1 and CD147.Oncogene advance online publication, 4 April 2016; doi:10.1038/onc.2016.89. © 2016 Macmillan Publishers Limited


Li Y.X.,PLA Fourth Military Medical University
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2011

This study was aimed to investigate the expression of cdx2 gene in pediatric patients with acute leukemia and its clinical implication. The bone marrow and peripheral blood were collected from 33 newly diagnosed pediatric patients with acute leukemia, the cdx2 gene expression in each AL subtypes and normal controls was detected by RT-PCR, the relationship between cdx2 expression and response to treatment was observed. The results showed that the expression of cdx2 was positive in 25 out of 30 AL cases (83.3%), to be exact, in 20 of 21 ALL cases (95.2%) and in 5 of 9 AML cases (55.6%), which showed statistical difference (p < 0.05). The cdx2 mRNA could be detected also in 1 of 3 CML cases. However, no expression of cdx2 was observed in all normal control which revealed significant difference between patient group and normal control group. 21 AL patients with cdx2 positive expression (17 ALL and 4 AML patients) and 4 AL patients with cxd2 negative expression (1 ALL and 3 AML patients) all reached complete remission (CR) after treatment, which showed no correlation with CR rate. 8 patients with positive cdx2 expression were followed up. As a result, the cdx2 positive expression at initial diagnosis of patients remained positive at reaching CR, but it gradually turned to negative along with prolonging of CR, while the cdx2 negative expression at initial diagnosis of patients remained negative at CR in bone marrow level. It is concluded that cdx2 positive expression is observed in the majority of pediatric AL patients, even positive rate in ALL patients is higher than that in AML patients, while the cdx2 expression also can be observed in CML patients. The cdx2 positive expression is not related to the CR rate in AL patients.


He F.,Northwest University, China | Cao R.,Northwest University, China | Feng Z.,Beijing Normal University | Guan H.,Xijing Hospital | Peng J.,PLA Fourth Military Medical University
PLoS ONE | Year: 2013

Burn wounds are severely stressful events that can have a significant impact on the mental health of patients. However, the impact of burns on individuals with different personality traits can be different. The present study aimed to investigate the impact of dispositional optimism on the subjective well-being of burn patients, and mainly focused on the confirmation of the mediator role of psychological resilience. 410 burn patients from five general hospitals in Xi'an accomplished the revised Life Orientation Test, Connor-Davidson Resilience Scale, and Subjective Well-Being (SWB) scale. The results revealed that both dispositional optimism and psychological resilience were significantly correlated with SWB. Structural equation modelling indicated that psychological resilience partially mediated the relationship between dispositional optimism and SWB. The current findings extended prior reports and shed some light on how dispositional optimism influenced SWB. Limitations of the study were considered and suggestions for future studies were also discussed.


Shu M.M.,PLA Fourth Military Medical University
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2010

In order to profoundly understand the clinical and laboratorial characteristics and inducing factors of hemophagocytic lymphohistiocytosis syndrome (HLH), 28 HLH patients received from 2004 to 2009 years in our hospital were analyzed retrospectively. The results indicated that all of the patients had a history with prolonged fever (more than 1 week), pancytopenia, hepatosplenomegaly, elevated ferritin level, hypofibrinogen, and hemophagocytosis in bone marrow. HLH was the first characteristic sign of malignant lymphoma in 9 patients; 1 patient had a clinical manifestation similar to fulminant hepatic failure; severe psycho-abnormality occurred in 1 HLH patient and pronounced hemophagocytosis were detected in his cerebrospinal fluid; 1 patient was eventually diagnosed as having HLH by the findings in a lymph node biopsy showing obvious hemophagocytosis. Additionally, the analysis of underlying factors in 28 patients with HLH indicated 11 patients with EB virus-associated HLH, 11 with lymphoma-associated HLH, 2 with Leishmania-associated HLH, and 3 with autoimmune disease-associated HLH. It is concluded that HLH disease is characterised with high heterogenicity in both clinical features and inducing factors; in addition, the patients from a pasturing area should be paid attention to parasite infection such as leishmania.


Shi Z.,Xian Jiaotong University | Wei Q.,University of Toronto | Zhang M.,PLA Fourth Military Medical University | She J.,Xian Jiaotong University
Critical Reviews in Eukaryotic Gene Expression | Year: 2014

Bladder cancer (UBC) is a common cancer worldwide and has a high rate of recurrence and progression despite systemic therapy. The molecular mechanisms of UBC are not completely understood. MicroRNAs are noncoding RNA molecules of approximately 23 nucleotides that play important roles in multiple steps during the progression of UBC. Here, we review the expression profiles of miRNAs and their biological functions, regulation, and clinical implications in UBC. Either down-regulation or up-regulation of miRNAs occurs in UBC through epigenetic changes or defects of the biogenesis apparatus. Deregulation of miRNAs is involved in cell-cycle arrest, apoptosis, proliferation, metastasis, drug resistance, and other functions in UBC. A number of miRNAs, including urine miRNAs, have been associated with tumor type, stage, or patient survival, and miRNAs might be developed as diagnostic or prognostic markers. Better understanding of the roles of miRNAs in UBC will shed light on the molecular mechanisms of UBC. © 2014 Begell House, Inc.


Fu H.J.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2011

To explore the clinical significance and mechanism of soluble CD40 Ligand (sCD40L) and high sensitive C-reactive protein (hs-CRP) in patients with acute coronary syndrome(ACS). A total of 86 consecutive patients with ACS were included in the study, according to the selection criteria for diagnosis of acute coronary syndrome (ACS), 86 patients were divided into two groups: normal and the ACS, In all patients, sCD40L and CRP levels were evaluated within 12 h. the incidence of acute cardiovascular events were observed after two months follow-up. The ACS group was obviously higher than control group (P<0.01), AMI group slightly higher than the UA group but had no significant difference (P>0.05). sCD40L and hs-CRP group of cardiovascular events increased more than the normal group. Acute coronary syndrome patients with early peripheral serum levels of sCD40L and hs-CRP were significantly increased, suggesting that CD40/CD40L system participate the occurrence of ACS, and the inflammatory factors such as C-reactive protein in collaboration, plays an important role on atherosclerotic plaque instability.


Li Y.,PLA Fourth Military Medical University
The Journal of international medical research | Year: 2012

To investigate the role of vascular endothelial growth factor (VEGF) in haemorrhagic fever with renal syndrome (HFRS). VEGF, soluble VEGF receptor (sVEGFR)-2, angiopoietin (Ang)-1, tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels were measured in serum samples from 68 patients with HFRS. Cultured human umbilical vein endothelial cells (HUEVCs) were infected by Hantaan virus (HTNV) and/or stimulated with recombinant VEGF; dextran permeability of the cells was determined. Claudin-1 and vascular endothelial (VE)-cadherin levels were determined by real-time reverse transcription-polymerase chain reaction and Western blot analyses. Serum VEGF, TNF-α and IFN-γ levels were significantly elevated, whereas sVEGFR2 and Ang-1 levels were reduced, during the acute phase of HFRS. In vitro cell permeability was unaffected by HTNV infection or VEGF stimulation alone, but the combination of HTNV infection and VEGF treatment significantly increased the permeability of endothelial cell monolayers in a time-dependent manner. Claudin-1 and VE-cadherin were downregulated at both the mRNA and protein level by combined HTNV infection and VEGF stimulation. Elevated VEGF induced by HTNV infection may play an important role in the vascular hyperpermeability that is characteristic of HFRS.


Liang L.,University of Pennsylvania | Liang L.,PLA Fourth Military Medical University | Wei H.,University of Pennsylvania
Alzheimer Disease and Associated Disorders | Year: 2015

Alzheimer disease (AD) is a fatal progressive disease and the most common form of dementia without effective treatments. Previous studies support that the disruption of endoplasmic reticulum Ca2+ through overactivation of ryanodine receptors plays an important role in the pathogenesis of AD. Normalization of intracellular Ca2+ homeostasis could be an effective strategy for AD therapies. Dantrolene, an antagonist of ryanodine receptors and an FDA-approved drug for clinical treatment of malignant hyperthermia and muscle spasms, exhibits neuroprotective effects in multiple models of neurodegenerative disorders. Recent preclinical studies consistently support the therapeutic effects of dantrolene in various types of AD animal models and were summarized in the current review. © 2014 Wolters Kluwer Health, Inc. All rights reserved.


Guo S.,PLA Fourth Military Medical University
Leukemia | Year: 2015

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation. We have identified recurrent mutations in CD28 in PTCLs. Two residues—D124 and T195—were recurrently mutated in 11.3% of cases of AITL and in one case of PTCL, not otherwise specified (PTCL-NOS). Surface plasmon resonance analysis of mutations at these residues with predicted differential partner interactions showed increased affinity for ligand CD86 (residue D124) and increased affinity for intracellular adaptor proteins GRB2 and GADS/GRAP2 (residue T195). Molecular modeling studies on each of these mutations suggested how these mutants result in increased affinities. We found increased transcription of the CD28-responsive genes CD226 and TNFA in cells expressing the T195P mutant in response to CD3 and CD86 co-stimulation and increased downstream activation of NF-κB by both D124V and T195P mutants, suggesting a potential therapeutic target in CD28-mutated PTCLs.Leukemia advance online publication, 22 January 2016; doi:10.1038/leu.2015.357. © 2015 Macmillan Publishers Limited


Tian Y.,University of Pennsylvania | Tian Y.,Temple University | Liu Y.,University of Pennsylvania | Wang T.,University of Pennsylvania | And 15 more authors.
Science Translational Medicine | Year: 2015

In contrast to lower vertebrates, the mammalian heart has limited capacity to regenerate after injury in part due to ineffective reactivation of cardiomyocyte proliferation. We show that the microRNA cluster miR302-367 is important for cardiomyocyte proliferation during development and is sufficient to induce cardiomyocyte proliferation in the adult and promote cardiac regeneration. In mice, loss of miR302-367 led to decreased cardiomyocyte proliferation during development. In contrast, increased miR302-367 expression led to a profound increase in cardiomyocyte proliferation, in part through repression of the Hippo signal transduction pathway. Postnatal reexpression of miR302-367 reactivated the cell cycle in cardiomyocytes, resulting in reduced scar formation after experimental myocardial infarction. However, long-term expression of miR302-367 induced cardiomyocyte dedifferentiation and dysfunction, suggesting that persistent reactivation of the cell cycle in postnatal cardiomyocytes is not desirable. This limitation can be overcome by transient systemic application of miR302-367 mimics, leading to increased cardiomyocyte proliferation and mass, decreased fibrosis, and improved function after injury. Our data demonstrate the ability of microRNA-based therapeutic approaches to promote mammalian cardiac repair and regeneration through the transient activation of cardiomyocyte proliferation. © 2015, American Association for the Advancement of Science. All rights reserved.


Li Y.-N.,Xian Jiaotong University | Pan R.,University of New Mexico | Qin X.-J.,PLA Fourth Military Medical University | Yang W.-L.,Xian Jiaotong University | And 5 more authors.
Journal of Neurochemistry | Year: 2014

Blood-brain barrier (BBB) disruption occurring within the first few hours of ischemic stroke onset is closely associated with hemorrhagic transformation following thrombolytic therapy. However, the mechanism of this acute BBB disruption remains unclear. In the neurovascular unit, neurons do not have direct contact with the endothelial barrier; however, they are highly sensitive and vulnerable to ischemic injury, and may act as the initiator for disrupting BBB when cerebral ischemia occurs. Herein, we employed oxygen-glucose deprivation (OGD) and an in vitro BBB system consisting of brain microvascular cells and astrocytes to test this hypothesis. Neurons (CATH.a cells) were exposed to OGD for 3-h before co-culturing with endothelial monolayer (bEnd 3 cells), or endothelial cells plus astrocytes (C8-D1A cells). Incubation of OGD-treated neurons with endothelial monolayer alone did not increase endothelial permeability. However, when astrocytes were present, the endothelial permeability was significantly increased, which was accompanied by loss of occludin and claudin-5 proteins as well as increased vascular endothelial growth factor (VEGF) secretion into the conditioned medium. Importantly, all these changes were abolished when VEGF was knocked down in astrocytes by siRNA. Our findings suggest that ischemic neurons activate astrocytes to increase VEGF production, which in turn induces endothelial barrier disruption. © 2013 International Society for Neurochemistry.


Guo H.,Thomas Jefferson University | Guo H.,PLA Fourth Military Medical University | Li Q.,Thomas Jefferson University | Chou D.W.,Thomas Jefferson University | Uitto J.,Thomas Jefferson University
Journal of Molecular Medicine | Year: 2013

Pseudoxanthoma elasticum (PXE), a multisystem heritable disorder with aberrant mineralization of arterial blood vessels, is caused by mutations in the ABCC6 gene. Previous studies have suggested that carriers of the ABCC6 mutations, particularly of p.R1141X, are at increased risk for coronary artery disease. In this study, we used Abcc6 tm1Jfk knock-out mice to determine the serum lipid profiles and examine the effects of atorvastatin on the aberrant mineralization in this model of PXE. First, serum lipid profiles at 12 weeks of age, after overnight fasting, revealed a statistically significant increase in total cholesterol and triglyceride levels in Abcc6 tm1Jfk mice compared to their wild-type littermates. Placing these mice at 4 weeks of age for 20 weeks on atorvastatin, either 0.01 % or 0.04 % of the diet (low statin and high statin groups, respectively), reduced the total triglyceride and cholesterol levels, which was accompanied with significantly reduced mineralization of the dermal sheath of vibrissae, a biomarker of the aberrant mineralization process in these mice. However, if the mice were placed on atorvastatin for 12 weeks at 12 weeks of age, at which time point significant mineralization had already taken place, no difference in the amount of mineralization was noted. These observations suggest that statins, particularly atorvastatin, can prevent, but not reverse, aberrant mineralization in this mouse model of PXE. For a clinical perspective, a survey of 1,747 patients with PXE was conducted regarding their present or past use of statins. The results indicated that about one third of all PXE patients are currently or have previously been on cholesterol-lowering drugs. Thus, a sizable number of patients with PXE could be subject to modulation of their mineralization processes by concomitant statin treatment. Key message: The Abcc6 -/- mice serve as a model system for PXE, an ectopic mineralization disorder Abcc6 -/- mice were shown to have elevated serum cholesterol and triglyceride levels Feeding of the Abcc6 -/- mice with atorvastatin prevented connective tissue mineralization A third of patients with PXE was found to be on cholesterol-lowering therapy Atorvastatin may potentially be beneficial for patients with PXE © 2013 Springer-Verlag Berlin Heidelberg.


Zhang B.,Chinese Peoples Liberation Army | Liu T.,PLA Fourth Military Medical University | Wu T.,Chinese Peoples Liberation Army | Wang Z.,Chinese Peoples Liberation Army | And 2 more authors.
International Journal of Biological Macromolecules | Year: 2015

Our previous study demonstrated that the overexpression of solute carrier family 22 member 18 (SLC22A18) in human non-small cell lung cancer (NSCLC) tissues might be associated with tumor progression and patients' prognosis. The aim of this study was to investigate the molecular mechanisms underlying its roles in NSCLC. As a result, bioinformatics analysis and luciferase reporter assay showed that microRNA (miRNA)-137 directly targeted SLC22A18 in NSCLC cells. Then, functional studies indicated that the ectopic expression of miR-137 significantly inhibited NSCLC cell proliferation, invasion and migration by targeting SLC22A18. More importantly, the decreased expression of miR-137 in clinical NSCLC tissues was correlated with advanced TNM stage, positive metastasis and poor prognosis of patients with this malignancy. In conclusion, these findings offer the convincing evidence that the roles of SLC22A18 in NSCLC progression may be partially caused by the regulatory effects of miR-137, which may function as a tumor suppressor. Our clinical data further indicated that miR-137 may be an independent favorable prognostic factor in NSCLC patients. © 2014 Elsevier B.V.


Yang J.,Albany Medical College | Yang J.,PLA Fourth Military Medical University | Bai Y.,Albany Medical College | Zhang Y.,Albany Medical College | And 3 more authors.
Molecular Microbiology | Year: 2014

Summary: Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide. The pathogenesis by the causative agent, Mycobacterium tuberculosis, is still not fully understood. We have previously reported that M. tuberculosisRv3586 (disA) encodes a diadenylate cyclase, which converts ATP to cyclic di-AMP (c-di-AMP). In this study, we demonstrated that a protein encoded by Rv2837c (cnpB) possesses c-di-AMP phosphodiesterase activity and cleaves c-di-AMP exclusively to AMP. Our results showed that in M. tuberculosis, deletion of disA abolished bacterial c-di-AMP production, whereas deletion of cnpB significantly enhanced the bacterial c-di-AMP accumulation and secretion. The c-di-AMP levels in both mutants could be corrected by expressing the respective gene. We also found that macrophages infected with ΔcnpB secreted much higher levels of IFN-β than those infected with the wild type (WT) or the complemented mutant. Interestingly, mice infected with M. tuberculosis ΔcnpB displayed significantly reduced inflammation, less bacterial burden in the lungs and spleens, and extended survival compared with those infected with the WT or the complemented mutant. These results indicate that deletion of cnpB results in attenuated virulence, which is correlated with elevated c-di-AMP levels. © 2014 John Wiley & Sons Ltd.


Lu L.,PLA Fourth Military Medical University
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2010

To retrospectively analysis the clinical data of facial nerve defects repair with greater auricular nerve graft. The transmastoid approach was adopted to repair the facial nerve defects by means of nerve grafting. Preoperative and postoperative facial nerve functions were graded according to the House-Brackmann scale. The patterns of temporal bone fracture in the 8 patients were longitudinal, most lesions occurred in the region of the second genu and its surrounding, preoperatively, all patients had Grade VI function. In 3 patients of facial nerve tumors, the tumors involved multiple nerve segments, and histologic results were all schwannomas, preoperatively, 1 case had Grade III function, 2 cases had Grade V function. In 2 patients of iatrogenic trauma of the facial nerve, the primary disease was chronic otitis media with cholesteatoma, the lesions were localized at the mastoid segment and the second genu respectively. In 1 patient of molten steel burn, the lesions was localized at the tympanic segment, preoperative facial nerve function was Grade VI. In addition to 3 cases lost to follow-up, the remaining patients, 4 recovered to a Grade III, 3 to a Grade VI, 2 to a Grade V and 2 remained at Grade VI. In present study, the most common cause of facial nerve transection was temporal bone fracture. Facial nerve reconstruction by means of greater auricular nerve grafting was a practical and effective method, the best postoperative recovery of facial nerve function was Grade III.


Ma X.J.,PLA Fourth Military Medical University
Zhonghua zheng xing wai ke za zhi = Zhonghua zhengxing waike zazhi = Chinese journal of plastic surgery | Year: 2010

OBJECTIVE: To investigate the application of expanded deltopectoral flaps for treatment of cervical cicatricial contracture. METHODS: The cervical cicatricial contracture was corrected in 18 cases with unilateral expanded deltopectoral flaps and 2 cases with bilateral expanded deltopectoral flaps. The size of scar ranged from 8 cm x 5 cm to 12 cm x 13 cm. The size of the unilateral expanded deltopectoral flaps ranged from 9 cm x 16 cm to 12 cm x 18 cm. The defects in donor sites were closed directly. The infraclavicula incision was designed. The flaps were delayed 3 weeks after flap transfer. The pedicle was cut off 4 weeks later. RESULTS: From 2007 to 2009, 20 cases with cervical cicatricial contracture were treated with expanded deltopectoral flaps. All the flaps were survived. 6 cases were followed up for 6 months with satisfactory results in 5 cases and conspicuous scar in 1 case. CONCLUSIONS: Expanded deltopectoral flap is very suitable for large size of cervical cicatricial contracture.


Wang Y.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2012

To construct and express a trichosanthin (TCS) gene mutant and purify the expressed product in E.coli. The potential antigenic determinant was predicted on TCS molecule by computer modeling and induced for site-directed mutation. The gene mutant TCS(FYY163-165CSA); was amplified by PCR using the genomic DNA of Trichosanthes kirilowii as a template and cloned into expression vector pRSET-A, then transfected into E.coli BL21 (DE3) for expression by inducing with IPTG. The expressed product was identified by Western blotting and purified by Ni-NTA affinity column chromatography. The soluble target protein was successfully expressed in E.coli. Homogenous TCS mutant protein was obtained after purification of expressed product. The site-directed mutagenesis, expression and purification of TCS provide a new approach for reconstructing TCS.


Wu J.,PLA Fourth Military Medical University
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2010

To investigate the clinical and diagnostic characteristics of audiometric findings and vestibular-evoked myogenic potentials in patients with large vestibular aqueduct syndrome (LVAS). Thirty LVAS subjects (60 ears) recruited received pure tone audiometry, acoustic immittance, auditory brain stem responses (ABRs), distortion-product otoacoustic emission (DPOAE), Vestibular evoked myogenic potentials (VEMP) and caloric test, and the diagnostic significance of the results was analyzed. All 30 cases (60 ears) showed progressive and fluctuating hearing loss, while 16 cases experienced dizziness when hearing fluctuated. Most of our cases showed sensorineural hearing loss, and 47 ears (94.0%) showed air-bone gap in the low frequencies, with mean gaps of (43 +/- 17) dB HL at 250 Hz, (33 +/- 18) dB HL at 500 Hz, in which the middle ear function showed normal. The acoustically evoked short latency negative response (ASNR) with medium latency (3.06 +/- 0.52) ms was elicited from 18 ears (64.3%). The mean amplitude of vestibular evoked myogenic potentials (VEMP) of 42 ears was (147.10 +/- 107.55) microv, and the threshold of VEMP of 19 ears was 75 dB nHL, of 7 ears was 65 dB nHL. Characteristics of hearing performance, such as progressive and fluctuating hearing loss, air-bone gap at the low frequencies with normal middle ears, the ASNR, and increased amplitude and decreased threshold of the VEMPs, will help clinicians make initial diagnosis of LVAS, and provide a reference for further imaging examination.


Tang L.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2011

To establish a ubiquitously expressed PD-L1 transgenic mouse model and evaluate its recovery of motor function after spinal cord injury. Clone and sequence the complete mouse PD-L1 cDNA and construct the pCAG-PD-L1 transgenic vector by inserting the PD-L1 cDNA into the pCAGGS vector. The PD-L1 transgenic (TgPD-L1) mice were established by pronuclear micro-injection with fertilized eggs from C57BL/6 mice and the genotypes were confirmed by PCR with tail genomic DNA. The expression of PD-L1 on T and B lymphocytes from mouse spleen were detected by flow cytometry. The expression of PD-L1 in peripheral tissues was displayed by immunohistochemistry. The expression level of PD-L1 in spinal tissue was evaluated by RT-PCR. The recovery of motor function was analyzed by Basso-Beattie-Bresnahan(BBB) locomotion testing system at 3, 7, 14, 21, 28 and 35 day after spinal severe crush with forceps in mice. Three lines of TgPD-L1 mice in C57BL/6 background were generated and the exogenous PD-L1 gene can be heritable steadily to offsprings. PD-L1 was highly exppressed in spinal tissue, peripheral tissues, T and B lymphocytes using RT-PCR, immunohistochemistry and flow cytometry respectively in TgPD-L1 mice. The BBB scores were obviously higher at 21 day post-injury in TgPD-L1 than those of in WT mice (P<0.05). The TgPD-L1 mice whose background are C57BL/6 were established successfully and high expression level of PD-L1 in tissues promotes locomotion recovery after spinal cord injury in TgPD-L1 mice.


Li C.,Northwestern Polytechnical University | Li Q.,PLA Fourth Military Medical University | Mei Q.,Northwestern Polytechnical University | Lu T.,Northwestern Polytechnical University
Life Sciences | Year: 2015

Herba Epimedii is an important medicinal plant which has been used in various traditional Chinese formulations for thousands of years as well as in modern proprietary traditional Chinese medicine products. It has extensive clinical indications, especially for the treatment of sexual dysfunction and osteoporosis. There have been more than 260 chemical moieties identified in the genus Epimedium most of which belong to flavonoids. Icariin is the most abundant constituent in Herba Epimedii. Icariin is pharmacologically bioactive and demonstrates extensive therapeutic capacities such as osteoprotective effect, neuroprotective effect, cardiovascular protective effect, anti-cancer effect, anti-inflammation effect, immunoprotective effect and reproductive function. Particularly, the significant osteogenic effect of icariin made it a promising drug candidate in bone tissue engineering. The current review paper aims to summarize the literatures reporting the pharmacological effects of icariin. The pharmacokinetic properties of bioactive ingredients in Herba Epimedii have also been discussed. © 2015 Elsevier Inc.


Shang F.J.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2011

To investigate the role of p38 mitogen-activated protein kinase(MAPK) in lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) expression in neonatal rat cardiomyocytes and to determine the relationship between reactive oxygen species (ROS) and p38 MAPK activation. Cardiomyocytes were isolated from neonatal Sprague-Dawley rats and cultured by differential adhesion. Expression of TNF-α was determined in culture medium by ELISA. Activation of p38 MAPK was determined by Western blot analysis with phospho-specific antibody. ROS generation in cardiomyocytes was determined by peroxide specific probe 2', 7'-dichlorofluorescin diacetate (DCF-DA). In cardiomyocytes stimulated with LPS, the content of TNF-α in culture medium correlated with the activity of p38 MAPK in a time-dependent manner. The activation of p38 was observed after stimulation of 1 mg/L LPS for 1 h. TNF-α accumulated significantly in culture medium at 3 h after stimulation of LPS (P<0.05), which was remarkably attenuated by pretreatment with p38 MAPK specific inhibitor SB203580 (P<0.01). Furthermore, the production of ROS in cardiomyocytes stimulated with LPS was also increased at 1 h after stimulation of LPS, consistent with p38 MAPK activity. Pretreatment with antioxidants such as N-acetylcysteine and diphenyleneiodonium significantly inhibited the activation of p38 MAPK compared with LPS control (P<0.05). There was no significance in the activity of p38 MAPK among antioxidants pretreatment and non-LPS control groups. The activation of p38 MAPK plays an important role in TNF-α expression in LPS-stimulated cardiomyocytes and the increase of ROS production is prerequisite for the activation of p38 MAPK.


Su J.,PLA Fourth Military Medical University | Liu Y.-C.,La Jolla Institute for Allergy and Immunology
Seminars in Immunopathology | Year: 2010

Regulatory T cells (Tregs) play a critical role in maintaining immune tolerance to self-antigens, whose development and activation is controlled by the master regulator and transcription factor Foxp3. Foxp3 acts as transcription repressor and exerts its suppressing function via directly associating with and inhibiting the function of other transcriptional regulators. The gene transcription of Foxp3 is regulated by diverse mechanisms at the cellular and molecular levels including the pleiotropic cytokine transforming growth factor-β (TGF-β). Itch is an E3 ubiquitin ligase whose deficiency is linked to excessive immune responses, abnormal T helper cell differentiation, and failed T cell anergy induction. Recent evidence indicates that Itch is involved in TGF-β-induced Foxp3 expression and Treg-regulated airway inflammation, thus identifying a ubiquitin-dependent pathway in modulating Tregs. © 2010 Springer-Verlag.


Li Z.,PLA Fourth Military Medical University
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2010

To investigate the prevalence of vertigo and related risk factors in middle school students in the city of Xi'an. A cross-section study was used to investigate on vertigo among middle school students. Questionnaire ,ear examination and auditory tests were carried out by the staff who received special training. Multiple Logistic regression models were used to analyze the relative influential factors about vertigo. There were 1567 middle school students who underwent a complete investigation. The participants comprised 793 males (50.6%) and 774 females (49.4%). The overall prevalence of vertigo was 5.6%. No significant difference of the prevalence was found between males (4.7%) and females (6.5%) (P > 0.05). The use of MP3 or MP4, insomnia and history of middle ear infections or ototoxic drugs ingestion were the main risk factors for vertigo (odds ratio: 2.837, 5.582, 2.808 and 1.695, respectively). Vertigo has an influence on the study and living of the students. More researches are urgently needed on prevention and treatment of vertigo.


Zhang J.,PLA Fourth Military Medical University | Zhang J.,University of Houston | Liu J.,University of Houston
Pharmacology and Therapeutics | Year: 2013

Cancer is not only composed malignant epithelial component but also stromal components such as fibroblasts, endothelial cells, and inflammatory cells, by which an appropriate tumor microenvironment (TME) is formed to promote tumorigenesis, progression, and metastasis. As the most abundant component in the TME, cancer-associated fibroblasts (CAFs) are involved in multifaceted mechanistic details including remodeling the extracellular matrix, suppressing immune responses, and secreting growth factors and cytokines that mediate signaling pathways to extensively affect tumor cell growth and invasiveness, differentiation, angiogenesis, and chronic inflammatory milieu. Today, more and more therapeutic strategies are purposefully designed to target the TME as well as tumor cells. This review will focus on the role of CAFs in tumor development and the novel strategies to target this component to inhibit the tumor growth. © 2012 Elsevier Inc. All rights reserved.


Xiang-qiang L.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2011

To investigate the expression and clinical significance of FOXO4 in colorectal cancer tissues. Immunohistochemistry assay was performed to detect the FOXO4 expression in 80 colorectal cancer and matched noncancerous tissues (18 cases in stage I, 32 in stage II, 24 in stage III and 6 in stage IV). The relationship between FOXO4 expression and the patients' clinicopathologic features including gender, differentiation and TNM staging was also analyzed. The positive expression rate of FOXO4 protein in colorectal cancer tissues was 47.50%, which was significantly lower than that in matched noncancerous tissues (91.25%, P0.05) . however, there were significant differences of FOXO4 expression in tumor differentiation, TNM stage and lymph node metastasis (P<0.05). The expression of FOXO4 was significantly decreased or deleted in colorectal cancer, indicating that FOXO4 may function as a tumor suppressor in the development and progression of colorectal cancer.


Liu H.,Beihang University | Li X.,Beihang University | Zhou G.,Beihang University | Fan H.,PLA Fourth Military Medical University | Fan Y.,Beihang University
Biomaterials | Year: 2011

One of the major downfalls of tissue-engineered small-diameter vascular grafts is the inability to obtain a confluent endothelium on the lumenal surface. Loosely attached endothelial cells (ECs) are easily separated from the vessel wall when exposed to the in vivo vascular system. Thus any denuded areas on the lumenal surface of vascular grafts may lead to thrombus formation via platelet deposition and activation. If the denuded areas could express anticoagulant activity until the endothelial cell lining is fully achieved, it may greatly improve the chances of successful vascular reconstruction. In this study, we fabricate sulfated silk fibroin nanofibrous scaffolds (S-silk scaffolds) and assess the anticoagulant activity and cytocompatibility of S-silk scaffolds in vitro in order to improve the antithrombogenicity and get some insights into its potential use for vascular tissue engineering. Sulfated silk fibroin was prepared by reaction with chlorosulphonic acid in pyridine, and then was developed to form an S-silk scaffold by electrospinning technique. FTIR analyses identified the successful incorporation of sulfate groups in silk fibroin molecules. It was found that the anticoagulant activity of S-silk scaffolds was significantly enhanced compared with silk fibroin nanofibrous scaffolds (Silk scaffolds). Vascular cells, including ECs and smooth muscle cells (SMCs), demonstrated strong attachment to S-silk scaffolds and proliferated well with higher expression of some phenotype-related marker genes and proteins. Overall, the data in this study suggest the suitability of S-silk scaffolds used along with vascular cells for the development of tissue-engineered vascular grafts. © 2011 Elsevier Ltd.


Wang Q.,CAS Lanzhou Institute of Chemical Physics | Wang Q.,PLA Fourth Military Medical University | Su Y.,CAS Lanzhou Institute of Chemical Physics | Li L.,CAS Lanzhou Institute of Chemical Physics | Huang H.,CAS Lanzhou Institute of Chemical Physics
Chemical Society Reviews | Year: 2016

Transition-metal catalysed C-N bond activation has attracted much attention and become one of the most promising bond disconnection and formation strategies that encompass a broad spectrum of applications in many reactions. In this tutorial review, efficient strategies for catalytic cleavage of C(sp)-N, C(sp2)-N and C(sp3)-N bonds and their applications in new C-C and C-N bond formation reactions are summarized. © The Royal Society of Chemistry 2016.


Chen F.-Q.,Medical University of South Carolina | Chen F.-Q.,PLA Fourth Military Medical University | Zheng H.-W.,Medical University of South Carolina | Schacht J.,University of Michigan | Sha S.-H.,Medical University of South Carolina
PLoS ONE | Year: 2013

This study delineates the role of peroxiredoxin 3 (Prx3) in hair cell death induced by several etiologies of acquired hearing loss (noise trauma, aminoglycoside treatment, age). In vivo, Prx3 transiently increased in mouse cochlear hair cells after traumatic noise exposure, kanamycin treatment, or with progressing age before any cell loss occurred; when Prx3 declined, hair cell loss began. Maintenance of high Prx3 levels via treatment with the radical scavenger 2,3-dihydroxybenzoate prevented kanamycin-induced hair cell death. Conversely, reducing Prx3 levels with Prx3 siRNA increased the severity of noise-induced trauma. In mouse organ of Corti explants, reactive oxygen species and levels of Prx3 mRNA and protein increased concomitantly at early times of drug challenge. When Prx3 levels declined after prolonged treatment, hair cells began to die. The radical scavenger p-phenylenediamine maintained Prx3 levels and attenuated gentamicin-induced hair cell death. Our results suggest that Prx3 is up-regulated in response to oxidative stress and that maintenance of Prx3 levels in hair cells is a critical factor in their susceptibility to acquired hearing loss. © 2013 Chen et al.


Ma Y.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2010

To establish ELISA method for quantitate the concentration of cystatin C (cys C) and to monitor the renal function of patients before and after renal transplantation. Hybridomas secreting monoclonal antibodies (mAbs) against human cys C were produced and sandwich ELISA kit for quantitatively detecting cys C was established. Then the concentrations of serum cystatin C (Scys C) and urine cystatin C (Ucys C) from normal controls and 23 patients undergoing renal transplantation were detected and their relationship with serum creatinine (SCR) was analyzed. Seven hybridomas secreting anti-cys C mAbs were obtained. The sensitivity of the established ELISA kit reached 0.1 μg/L. The concentrations of Scys C and Ucys C of normal healthy controls were in accordance with other report. High correlations between Scys C or Ucys C and the level of SCR were observed (P<0.01). Rapid decline of Scys C and Ucys C concentrations was consistent with the decrease of SCR in the patients with normal course (NC) recovery after renal transplantation. However, Ucys C kept higher level within two weeks after the operation in patients with AR until the day 21. In patients with DGF, higher levels of Scys C, Ucys C and SCR were sustained within four weeks after renal transplantation. The sensitive ELISA kit for detection of cys C has been established. Importantly, there are the persistently high levels of Scys C and Ucys C in patients with AR or DGF, which can be used as a novel indicator for monitoring renal function after renal transplantation.


Zhou J.,Urumqi General Hospital of PLA | Zeng P.,Urumqi General Hospital of PLA | Tu H.H.,Institute for Drug and Instrument of Xinjing Miltary Command | Wang F.Q.,PLA Fourth Military Medical University
Journal of Separation Science | Year: 2011

A simple, rapid and specific method based on cloud-point extraction (CPE) was developed to determine ampelopsin in rat plasma after oral administration by reversed-phase high-performance liquid chromatography. The non-ionic surfactant Genapol X-080 was chosen as the extract solvent. Some important parameters affecting the CPE efficiency, such as the nature and concentration of surfactant, extraction temperature and time, centrifuge time and salt effect, were investigated and optimized. Separation was accomplished using a C 18 column by gradient elution with a acetonitrile-phosphate buffer solution as the mobile phase. The detection wavelength was set at 290 nm. Under optimum conditions, the linear range of ampelopsin in rat plasma was 20-2000 ng/mL (r2=0.9996). The limit of detection was 6 ng/mL (S/N=3) with the limit of quantification being 20 ng/mL (S/N=10). The proposed method has been successfully applied for pharmacokinetic studies of ampelopsin from rat plasma after oral administration. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Yang Z.X.,U.S. National Institutes of Health | Yang Z.X.,PLA Fourth Military Medical University | Zhou Y.N.,U.S. National Institutes of Health | Yang Y.,U.S. National Institutes of Health | And 2 more authors.
Molecular Microbiology | Year: 2010

Helicobacter pylori persists deep in the human gastric mucus layer in a harsh, nutrient-poor environment. Survival under these conditions depends on the ability of this human pathogen to invoke starvation/stress responses when needed. Unlike many bacteria, H. pylori lacks starvation/stress-responding alternative sigma factors, suggesting an additional mechanism might have evolved in this bacterium. Helicobacter pylori produces polyphosphate; however, the role and target of polyphosphate during starvation/stress have not been identified. Here we show that polyphosphate accumulated during nutrient starvation directly targets transcriptional machinery by binding to the principal sigma factor in H. pylori, uncovering a novel mechanism in microbial stress response. A positively charged Lys-rich region at the N-terminal domain of the major sigma factor is identified as the binding region for polyphosphate (region P) in vivo and in vitro, revealing a new element in sigma 70 family proteins. This interaction is biologically significant because mutant strains defective in the interaction undergo premature cell death during starvation. We suggested that polyphosphate is a second messenger employed by H. pylori to mediate gene expression during starvation/stress. The putative 'region P' is present in sigma factors of other human pathogens, suggesting that the uncovered interaction might be a general strategy employed by other pathogens. © Published 2010. This article is a US Government work and is in the public domain in the USA.


Hann H.-W.,Thomas Jefferson University | Wan S.,Thomas Jefferson University | Myers R.E.,Thomas Jefferson University | Hann R.S.,Thomas Jefferson University | And 3 more authors.
PLoS ONE | Year: 2012

Background: Serum liver enzymes are frequently tested in clinics to aid disease diagnosis. Large observational studies indicated that these enzymes might predict cancer risk and mortality. However, no prospective study has reported on their relationships with the risk of HBV-related hepatocellular carcinoma (HCC). Methodology/Principal Findings: We evaluated the predictive values of four routinely tested liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and gamma-glutamyltransferase [GGT]) in HCC risk in a prospectively enrolled clinical cohort of 588 Korean American HBV patients. For all four enzymes, the baseline level as well as the average and maximum levels during the first 1 or 2 years of follow-up were analyzed using multivariate Cox proportional hazards model. Patients were categorized into a normal or an elevated group based on the clinical cut-off of each enzyme. During a median follow-up of 7.5 years, 52 patients (incidence rate, 8.8%) developed HCC. The incidence rates were higher in the elevated groups for all four enzymes. The most significant finding was for GGT, with the highest incidence rate of 16.4% in the elevated group compared to 4.6% in the normal group (P<0.001). Compared to patients with normal baseline GGT, those with elevated GGT exhibited a significantly increased HCC risk with a hazards ratio (HR) of 2.60 (95% confidence interval [CI], 1.41-4.77, P = 0.002). Further analyses revealed a cumulative effect between baseline GGT and ALP (HR = 3.41, 95% CI 1.54-7.56, P = 0.003). Conclusions Significance: Serum GGT might predict HCC risk in HBV patients individually or jointly with other enzymes. © 2012 Hann et al.


Li X.B.,PLA Fourth Military Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2010

OBJECTIVE: To investigate the risk factors for the prognosis in patients with gastric cancer undergoing surgery. METHODS: Clinical data of 1031 cases who underwent gastric cancer resection from January 2003 to December 2007 were studied using univariable analysis and multivariable regression analysis. RESULTS: In 1031 cases,95 (9.2%) cases were early-stage gastric cancer. The other 936 (90.8%) cases were advanced gastric cancer. The tumor was resectable in 980 (95.1%) cases, of which 874 (84.8%) were curative resection,106 (10.3%) were palliative, and 51 (4.9%) were bypass procedures or laparotomy alone. The stage-specific 5-year survival rates were 93.2% (stage IA), 65.1%(stage IB), 52.3% (stage II), 41.4% (stage IIIA), 16.6% (stage IIIB) and 10.6% (stage IV), respectively. The 1-, 3- and 5-year survival rates were 80.2%, 58.0% and 48.2%, respectively. The independent risk factors associated with the prognosis of these patients were tumor size, serum albumin, curative resection, TNM staging and multidisciplinary treatment in both univariable and multivariable analyses. CONCLUSIONS: Early curative resection is the most important treatment for the patients with gastric cancer. Individualized surgical procedure combined with multidisciplinary treatment can improve the outcome. Tumor size, serum albumin level and TNM staging are important predictors of survival in patients with gastric cancer.


Gadani S.P.,University of Virginia | Walsh J.T.,University of Virginia | Smirnov I.,University of Virginia | Zheng J.,University of Virginia | And 2 more authors.
Neuron | Year: 2015

Inflammation is a prominent feature of CNS injury that heavily influences neuronal survival, yet the signals that initiate and control it remain poorly understood. Here we identify the nuclear alarmin, interleukin (IL)-33, as an important regulator of theinnate immune response after CNS injury. IL-33 is expressed widely throughout the healthy brain and is concentrated in white mater due to predominant expression in post-mitotic oligodendrocytes. IL-33 is released immediately after CNS injury fromdamaged oligodendrocytes, acting on local astrocytes and microglia to induce chemokines critical for monocyte recruitment. Mice lacking IL-33 haveimpaired recovery after CNS injury, which isassociated with reduced myeloid cell infiltrates anddecreased induction of M2 genes at the injury site. These results demonstrate a novel molecular mediator contributing to immune cell recruitment tothe injured CNS and may lead to new therapeuticinsights in CNS injury and neurodegenerative diseases. © 2015 Elsevier Inc.


Wang P.C.,PLA Fourth Military Medical University
Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology | Year: 2013

To evaluate the effect of subgingival scaling/root planning (SRP) and occlusal adjustment on clinical and occlusal parameters in teeth with chronic periodontitis and secondary occlusal trauma. Eighteen patients with chronic periodontitis and occlusal trauma were included and randomly divided into group A and group B. On day 0, group A was treated by full-mouth subgingival scaling and root planning, and group B was treated by occlusal adjustment in occlusal trauma site. On day 28, group A was treated by occlusal adjustment in occlusal trauma site, and group B was treated by full-mouth subgingival scaling and root planning. Probing depth (PD), attachment loss (AL), bleeding index (BI) were evaluated on 0, 28 and 56 d, and the occlusal time (OT) and the percentage of occlusal force were evaluated on 0, 28 and 56 d in occlusal trauma site. The data was statistically analyzed. In baseline, the PD[(4.42 ± 1.41) mm vs (4.36 ± 1.38) mm], AL [(2.75 ± 1.32) mm vs (2.63 ± 1.37) mm] and BI [(2.20 ± 0.81) vs (2.24 ± 0.89)] of the full-mouth showed no significant difference between the two groups (P > 0.05). There was no significant difference in PD [(5.21 ± 1.21) mm vs (5.08 ± 1.12) mm], AL [(4.94 ± 1.47) mm vs (4.89 ± 1.32) mm], BI [(2.61 ± 0.92) vs 2.50 ± 0.79)], OT [(1.29 ± 0.39) s vs (1.34 ± 0.35) s] and the percentage of occlusal force [(6.8 ± 2.1)% vs (7.4 ± 1.7)%] in occlusal trauma site between the two groups(P > 0.05). After SRP therapy, the PD,AL,BI and OT were significantly decreased (P < 0.05).The clinical parameters exhibited no significant difference after only occlusal adjustment(P > 0.05).On 56 d, the reduction in clinical parameters was not significantly different between the two groups(P > 0.05),however the reduction of OT and the change of the percentage of occlusal force in group A [(0.85 ± 0.41) s, (2.2 ± 2.2)%] were more significant than those in group B [(0.70 ± 0.38) s; (1.5 ± 1.6)%] (P < 0.05). After occlusal adjustment, the increase of OT in group A [(0.21 ± 0.11) s] was lower than that in group B [(0.67 ± 0.37) s]through the 28-day observation period (P < 0.05). Occlusal adjustment alone is inadequate for control and management of periodontitis.SRP therapy can eliminate the inflammation and decrease the OT of tooth with occlusal trauma.The combination of SRP and occlusal adjustment may achieve more stable results.


Wang P.,PLA Fourth Military Medical University
The Chinese journal of dental research : the official journal of the Scientific Section of the Chinese Stomatological Association (CSA) | Year: 2010

OBJECTIVE: To evaluate the application of cone-beam computed tomography (CBCT) in the detection of dental root fractures and to analyse the demographic profile of these fractures. METHODS: The study group comprised 398 teeth that were examined by CBCT for determining whether they had a root fracture. Patient characteristics were recorded, and the location, fractured roots, fracture types and three-dimensional images of the related skeletal structures were analysed. Two experienced oral radiologists independently analysed each case and reached a consensus, and the diagnosis was graded in one of the following three categories: fracture definitely present (FDP), fracture probably present (FPP) and no visible fracture (NVF). RESULTS: Among these teeth, 155 (39.0%) were diagnosed as FDP, 14 (3.5%) as FPP and 229 (57.5%) as NVF in the consensus reading. During follow-up, all teeth diagnosed as FDP and 4 of the 14 teeth diagnosed as FPP were intra-operatively demonstrated to be fractured. In FDP cases, 60.0% of the patients were aged from 50 to 69 years. In total, 107 FDP teeth were non-endodontically treated, and the remaining were endodontically treated with (n = 16) or without (n = 32) crown placement. The maxillary and mandibular molars were most frequently affected (81.9%). The fractured roots were mostly palatal (65.7%) in maxillary molars and mesial (84.2%) in mandibular molars. The fractures were characterised as vertical (n = 84), horizontal (n = 34), oblique (n = 5) and complicated (n = 32) fractures. CONCLUSION: The application of CBCT is valuable for the diagnosis of root fracture.


Fan Y.Z.,PLA Fourth Military Medical University
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2010

To study the effects of genistein on the proliferation, apoptosis induction and expression of related gene proteins of human colon cancer cells in vitro and in vivo, and its mechanisms of action. MTT colorimetric assay was used to detect the effects of genistein on the proliferation of human colon adenocarcinoma SW480 cells. Light and transmission electron microscopy were used to study the histological and ultrastructural changes. Flow cytometry was used to determine the effects of genistein on cell cycle and apoptosis. Flow cytometry and immunohistochemistry were used to determine the effects of genistein on apoptosis induction and expression of related gene proteins of colon cancer cells. The MTT colorimetric assay showed that genistein inhibited the proliferation of SW480 cells in a dose-dependent and time-dependent manner, and the highest inhibition rate was 60.2% after 80 microg/ml genistein treatment for 72 h. The light microscopy revealed that many genistein-treated cancer cells were shrunken, disrupted, or showing cytoplasmic vacuolization. The electron microscopic examination showed cell shrinkage, nuclear fragmentation and pronounced chromatin condensation, sometimes formed crescent chromatin condensation attached to the nuclear membrane. The results of flow cytometry showed that: after SW480 cells were treated with 0, 20, 40, 80 microg/ml genistein for 48 h, the FI values of PCNA were 1.49 +/- 0.02, 1.28 +/- 0.04, 1.14 +/- 0.03, and 0.93 +/- 0.08; the FI values of VEGF were 1.75 +/- 0.02, 1.34 +/- 0.06, 1.32 +/- 0.04, and 1.23 +/- 0.04; the fluorescence index (FI) values of p21 were 1.26 +/- 0.05, 1.36 +/- 0.06, 1.61 +/- 0.03, and 1.73 +/- 0.03, respectively. There were statistically significant differences between the control group and each treatment group (P < 0.05 or P < 0.01). The scores of immunohistochemical staining of PCNA and VEGF proteins were decreased, while p21 increased. There were statistically significant differences between the control group and each treatment group (P < 0.05 or P < 0.01). Genistein can inhibit the growth of colon cancer cells via apoptosis induction and cell cycle arrest at G(2)/M phase. The anti-tumor mechanisms of genistein may be related with the down-regulation of expression of VEGF and PCNA, and up-regulation of the expression of p21.


Sun B.,Beihua University | Pu B.,222nd Hospital of PLA | Chu D.,PLA Fourth Military Medical University | Chu X.,Beihua University | And 2 more authors.
Journal of Neuro-Oncology | Year: 2013

MicroRNAs are known as non-coding RNAs that regulate the expression of target mRNA. Accumulating evidence has indicated that microRNA expression in human malignancies can be utilized as a prognostic marker for patients. However, the prognostic value of miR-650 in human glioma has not been investigated yet. In the present investigation, we have recruited 168 cases glioma specimens and 21 normal control brain specimens. Quantitative real-time PCR was carried out to investigate the expression of miR-650. Kaplan-Meier analysis and Cox's proportional hazards model was used to evaluate the association of miR-650 with prognosis of glioma patients. Results showed that miR-650 expression was increased in glioma compared with normal control specimens (P < 0.001). It was also found that miR-650 expression was related to World Health Organization grade and Karnofsky performance score (KPS) for high expression was more frequently detected in glioma of high grade or low KPS score (P < 0.001). The prognosis of glioma with high miR-650 expression was significantly worse compared with that of glioma with low miR-650 expression. These results proved that miR-650 expression was a significant prognostic indicator in glioma, which may suggest new management of human glioma. © 2013 Springer Science+Business Media New York.


Meng Z.-J.,Zhengzhou Peoples Hospital | Tao K.,PLA Fourth Military Medical University
Oncology Research | Year: 2016

Reports show that the stathmin gene may have a close relationship with tumor chemotherapeutic sensitivity. However, the effect of stathmin-1 on the chemosensitivity of gastric cancer to docetaxel has not been clearly determined. siRNA targeting stathmin-1 was introduced. The cell growth inhibition, expression of associated proteins, cell cycle, and apoptosis were evaluated by MTT, Western blot, and flow cytometric assays, respectively. The influence of silencing stathmin-1 was detected in situ and in vivo. SGC7901/docetaxel cells are the drug-resistant cells. After silencing stathmin-1, the resistance index (RI) reduced to 3.41, the expressions of STMN-1, MDR1, and ERCC1 were downregulated, but caspase 3 was upregulated. Stathmin-1 siRNA could improve the chemosensitivity of gastric cancer cells to docetaxel, making the percentage of cells at the sub-G1 stage increase and promote apoptosis. The growth of transplantation tumor was significantly suppressed. Therefore, stathmin-1 might be a potential target for enhancing the chemosensitivity of gastric cancer. Copyright © 2016 Cognizant, LLC.


Shu F.,PLA Fourth Military Medical University
Chinese Journal of Biologicals | Year: 2015

Objective: To prepare, purify and identify the chimeric vims-like particles (VLPs) of HCV neutralizing epitopes and HBV S antigen. Methods: Four recombinant plasmids for chimeric expression of HCV neutralizing epitopes and HBV S antigen, pCI-HBSEl, pCI-HBSE2, pCI-HBSE3 and pCI-HBSE4, were transfected to HEK293T cells in mediation of liposome respectively, and the culture supernatants were collected 48 h later. The obtained self-assembled HBV VLPs chimerized with HCV neutralizing epitopes, named as VLPs-SEl, VLPs-SE2, VLPs-SE3 and VLPs-SE4 respectively, were purified by sucrose density gradient centrifugation, concentrated by dialysis, observed by electron microscopy, determined for HBsAg content by electrochemical luminescence assay, and tested for reactions with the sera of patients infected with HCV by ELISA. Results: Four kinds of chimeric VLPs were observed by electron microscopy, each at an size of about 22 nm. The HBsAg content in VLPs-SE2 with the highest concentration reached 5. 51 x 103 ng/ml, which met the needs for further study. The serum neutralizing antibody levels of patients infected with HCV. determined using pooled VLPs as coating antigen were slightly higher than those using single VLPs. Conclusion: The chimeric VLPs of HCV neutralizing epitopes and HBV S antigen was prepared successfully, which laid a foundation of further evaluation of the neutralizing antibody and its protective effect induced by VLPs in vivo.


Liu Y.,PLA Fourth Military Medical University
Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology | Year: 2013

To evaluate new bone formation and preliminary clinical outcomes following maxillary sinus floor augmentation with Bio-Oss alone. Nine patients were treated with ten maxillary sinus floor augmentations using Bio-Oss alone, and eighteen Straumann implants were placed. After five to eleven-month healing period at implant placement, cylindrical specimens were biopsied from the augmented area. The new bone formation of specimens was analyzed by histology and micro-computed tomography. Cone beam computed tomography (CBCT) scans were performed for measurements of residual crestal bone height under the sinus, the amount of increased height immediate after the augmentation and before implant insertion. To monitor stability changes, resonance frequency analysis was performed and implant stability quotient (ISQ) values were collected at implant placements (baseline,0 month), one month, three months and six months after placements. All implants were loaded six months after insertion and no failures were recorded. Compared to adjacent native bone, no significant differences of bone volume fraction were found in augmented area (P > 0.05), together with lower trabecular number (P < 0.05) and trabecular thickness (P < 0.01) as well as higher trabecular separation (P < 0.01) by microradiographic analysis.Histomorphometrically, there was no significant difference in the amount of new bone formation between the adjacent native bone and augmented area (P > 0.05). CBCT showed a bone height gain of (14.19 ± 2.02) mm immediate after augmentation, which stabilized at (13.68 ± 1.95) mm after bone healing period. Mean ISQ value was 71.94 ± 6.51 at baseline, decreased to 70.19 ± 6.38 at 1 month, and increased to 78.17 ± 3.83 at 3 month and 82.56 ± 3.20 at 6 month. The use of Bio-Oss as the sole graft is reliable and can lead to satisfactory bone formation and clinical outcome.


Lu Q.,PLA Fourth Military Medical University
The Chinese journal of dental research : the official journal of the Scientific Section of the Chinese Stomatological Association (CSA) | Year: 2013

The mandibular first molars mostly have two mesial canals. In this report, two cases of mandibular first molars with three mesial canals are presented. The middle mesial canal was detected under endodontic microscope and further confirmed by cone-beam computed tomography and angled radiography, respectively. The purpose of this paper was to highlight the possibility of an aberrant root canal in a mandibular first molar and to help reduce the failure rates of the dental pulp treatment of the mandibular first molar.


Zheng L.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2013

To investigate the immunoregulatory effect of autologous peripheral blood stem cells (PBSCs) transplantation on T lymphocytes and cytokines in patients with HBV-related end-stage liver disease. Flow cytometry was used to measure the percentages of Th1, Th2 and regulatory T cells (Treg) in peripheral blood. Enzyme-linked immunosorbent assay (ELISA) was performed to analyze the levels of serum IFN-γ, IL-6 and IL-10. Patients with HBV-related end-stage liver disease displayed significantly improved liver function after PBSCs transplantation. Statistically, after PBSCs transplantation, the percentages of Th2 and Treg in peripheral blood markedly increased, but serum IL-6 and IL-10 declined significantly. No significant differences were observed in the changes of Th1 and its cytokine, IFN-γ after transplantation. Autologous PBSCs transplantation can depress inflammation in liver by regulating immune microenvironment, which at least in part delineates the mechanism of stem cells-mediated therapeutic benefit on end-stage liver disease.


Fu J.F.,PLA Fourth Military Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To investigate the association of urinary albumin excretion rate (UAER) and hyperuricemia with macrovascular atherosclerosis in type 2 diabetic patients. Ninety-seven type 2 diabetic patients were divided into two groups according to the UAER, namely group A with UAER between 20 and 200 microg/min (n=63) and group B with UAER > or = 200 microg/min (n=34); the patients were also classified into hyperuricemia group (group C, n=59) and normal blood uric acid (BUA) group (group D, n=38). The disease course, BUA, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoproteins (HDL), UAER and arteria carotis intima-media thickness (IMT) were determined in these patients. The relationship of UAER and hyperuricemia with carotid arterial IMT was analyzed statistically. The levels of TG, TC, LDL and HDL showed no significant differences between the 4 groups (P>0.05). The disease course, BUA, UAER, and FBG levels and IMT in groups A and C were significantly higher than those in groups C and D (P<0.05), but no such differences were found between groups A and C or between groups B and D (P>0.05). Arotid arterial IMT was independently correlated to the disease course, BUA and UAER (r=0.201, 0.1999, 0.211, respectively, P<0.05), and a significant positive correlation was noted between BUA and UAER (r=0.221, P<0.05). Macrovascular atherosclerosis in type 2 diabetic patients is significantly correlated to the disease course, BUA and UAER levels, which can be used to evaluate and predict macrovascular atherosclerosis in type 2 diabetic patients.


Bao H.-G.,PLA Fourth Military Medical University
Chinese Journal of Cardiology | Year: 2013

Objective: To explore the effects of glutamine (Gln) induced heat shock protein 70 (Hsp70) overexpression on atrial fibrosis and connexin43 remodeling in isoprenaline (ISO) treated rats and related mechanisms. Methods: Forty male SD rats were randomly divided into five groups (n = 8 each group): control group, DMSO group, ISO 5 mg · kg-1 · d-1 group (Fibrosis group), ISO 5 mg · kg-1 · d-1 + Ala-Gin 0.75 mg · kg-1 · d-1 group (Intervention group) and ISO 5 mg · kg-1 · d-1+ QUE 100 mg · kg-1 · d-1 + Ala-Gin 0.75 mg · kg-1 · d-1 + DMSO group (QUE group). Rats were killed after 7 d. The Angll expression in myocardial tissue was detected by radioimmunoassay; myocardial fibrosis was observed by HE staining. Collagen volume fractions were quantified by Masson staining and as the indicators of atrial fibrosis. The expressions of Hsp70, p-JNK1/2/3, c-Jun and Cx43 were determined with immunohistochemical method. Results: Ang II content was similar between the control group [(68.51 ± 10.76) pg/L] and DMSO [(71.47 ±11.49) pg/L] group (P > 0.05), and significantly increased in fibrosis group [(211.25 ± 49.49)pg/L], intervention group[(185.32 ± 54.85) pg/L] and QUE[(189.90 ± 42.12) pg/L] group (P < 0.01 vs. control group). Atrial fibrosis was significantly higher in the fibrosis group [(29.485 ± 9.966)%] and QUE group[(25.060 ±8.581)%] but not in the intervention group[(7.861 ± 1.867)%] compared to control group [(6.842 ± 1.674)%] and DMSO group [(7.108 ± 1.343)%]. The expression of Hsp70 was similar among the control group (0.160 ± 0.023), DMSO group (0.163 ± 0.022), fibrosis group (0.166 ± 0.028) and QUE(0.168 ± 0.027) group (P > 0.05) while significantly upregulated in the intervention group (0.215 ± 0.018) (P < 0.01 vs. control group). The expressions of p-JNK1/2/3 and c-Jun were similar between control group(0.151 ± 0.016; 0.163 ± 0.022) and DMSO group(0.154 ±0.021; 0.164 ± 0.024) (P > 0.05), while significantly upregulated in fibrosis group (0.202 ± 0.025; 0.254 ± 0.044) and QUE group(0.196 ± 0.024; 0.251 ± 0.027) (P < 0.01 vs. control group)but not in intervention group(0.160 ± 0.025; 0.168 ± 0.024) were not changed obviously(P > 0.05 vs. control group). The content of Cx43 was similar between control group and DMSO group(0.231 ± 0.035 vs. 0.220 ± 0.032, P > 0.05), and was linearly distributed in intercalated disc of the cardiomyocytes, however, the content of Cx43 was significantly reduced (P < 0.01) and the Cx43 distribution was disordered in fibrosis group (0.163 ± 0.013) and QUE group (0.165 ± 0.024), while these changes were not found in intervention group. Conclusion: Glutamine could reduce the atrial fibrosis and Cx43 remodeling in isoprenaline-treated rats by up-regulating Hsp70 and inhibiting JNK signaling pathway activation through down-regulating p-JNK1/2/3 and c-Jun expression. Copyright © 2013 by the Chinese Medical Association.


Zhao Z.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2014

To investigate the expression and clinical significance of gastric dramatic down-related gene (GDDR) in gastric cancer and precancerous lesion tissues. Immunohistochemical staining was performed to detect the expression of GDDR in 240 cases of gastric tissues, including 40 cases of normal gastric mucosa (NGM), 40 cases of chronic superficial gastritis (CSG), 40 cases of chronic atrophic gastritis (CAG), 40 cases of intestinal metaplasia (IM), 20 cases of mild dysplasia (MD), 20 cases of severe dysplasia (SD) and 40 cases of gastric cancer (GC). The mean rank order of GDDR were 190.70, 182.70, 146.24, 104.40, 70.33, 47.20 and 40.20 in NGM, CSG, CAG, IM, MD, SD and GC, respectively. The expression of GDDR significantly decreased in CAG, IM, MD, SD and GC as compared with normal controls and CSG (P<0.01). The gradually down-regulated expression of GDDR is an early molecular event in the development of gastric cancer. GDDR may play an important role in the early diagnosis of gastric cancer and may be utilized as a molecular diagnostic marker and a new target of anti-tumor molecular therapy in early stage of gastric cancer.


Bai Y.,Albany Medical College | Bai Y.,PLA Fourth Military Medical University | Yang J.,Albany Medical College | Zarrella T.M.,Albany Medical College | And 3 more authors.
Journal of Bacteriology | Year: 2014

Cyclic di-AMP (c-di-AMP) has been shown to play important roles as a second messenger in bacterial physiology and infections. However, understanding of how the signal is transduced is still limited. Previously, we have characterized a diadenylate cyclase and two c-di-AMP phosphodiesterases in Streptococcus pneumoniae, a Gram-positive pathogen. In this study, we identified a c-di-AMP binding protein (CabP) in S. pneumoniae using c-di-AMP affinity chromatography. We demonstrated that CabP specifically bound c-di-AMP and that this interaction could not be interrupted by competition with other nucleotides, including ATP, cAMP, AMP, phosphoadenylyl adenosine (pApA), and cyclic di-GMP (c-di-GMP). By using a bacterial two-hybrid system and genetic mutagenesis, we showed that CabP directly interacted with a potassium transporter (SPD_0076) and that both proteins were required for pneumococcal growth in media with low concentrations of potassium. Interestingly, the interaction between CabP and SPD_0076 and the efficiency of potassium uptake were impaired by elevated c-di-AMP in pneumococci. These results establish a direct c-di-AMP-mediated signaling pathway that regulates pneumococcal potassium uptake. © 2014, American Society for Microbiology.


Yan Z.,PLA Fourth Military Medical University | Mas E.,University of Western Australia | Mori T.A.,University of Western Australia | Croft K.D.,University of Western Australia | Barden A.E.,University of Western Australia
Analytical Biochemistry | Year: 2010

The measurement of urinary F2-isoprostanes is noninvasive and widely used to assess in vivo oxidative stress in humans. Most studies measure urinary F2-isoprostanes in the free form; however, many eicosanoids are excreted as urine glucuronide conjugates. Using gas chromatography-mass spectrometry, we examined the extent of glucuronide conjugation of F2-isoprostanes in urine collected from healthy men (n=20) and women (n=15). Incubation of urine with exogenous glucuronidase led to F2-isoprostane concentrations that were approximately 40% higher than untreated samples (P<0.001). We conclude that a significant proportion of F2-isoprostanes in urine are conjugated as glucuronides. © 2010 Elsevier Inc.


Liu Y.,Chongqing Medical University | Zhao T.,PLA Fourth Military Medical University | Yang Z.,Chongqing Medical University | Li Q.,Chongqing Medical University
International Journal of Experimental Pathology | Year: 2014

Summary: There is accumulating evidence which demonstrates that chronic cerebral ischaemia can induce white matter lesions (WMLs), and microglia-activation-mediated cytokines and proteases releasing during the ischaemia might play a vital role in pathogenesis. In addition, hypoxia-induced upregulated expression of fractalkine promotes the activation of microglia and their migration to the lesions through interaction with its receptor CX3CR1. However, the specific mechanisms involved in fractalkine/CX3CR1-mediated microglial activation have not been fully identified. In the present study, we constructed lentivirus encoding shRNA against CX3CR1 and transduced into microglial cells in under hypoxic conditions. Moreover, we analysed the proliferation, cytokine secretion and signal-pathway activation of the microglia. We found that CX3CR1 RNAi-mediated gene downregulation could attenuate hypoxic-induced microglial proliferation, cytokine secretion [including tumuor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)] and matrix metalloproteinase-2 (MMP-2) synthesis. These effects were shown to be nediated through p38MAPK/PKC activation. Therefore, our results reveal a novel mechanism of fractalkine/CX3CR1 involvement in activation of microglia. Thus CX3CR1 RNAi might provide a therapeutic strategy which could be useful in chronic cerebral ischaemia. © 2014 International Journal of Experimental Pathology.


Wang W.,Tsinghua University | Lv N.,Tsinghua University | Zhang S.,Tsinghua University | Shui G.,National University of Singapore | And 8 more authors.
Nature Medicine | Year: 2012

Adequate lipid secretion by mammary glands during lactation is essential for the survival of mammalian offspring. However, the mechanism governing this process is poorly understood. Here we show that Cidea is expressed at high levels in lactating mammary glands and its deficiency leads to premature pup death as a result of severely reduced milk lipids. Furthermore, the expression of xanthine oxidoreductase (XOR), an essential factor for milk lipid secretion, is markedly lower in Cidea-deficient mammary glands. Conversely, ectopic Cidea expression induces the expression of XOR and enhances lipid secretion in vivo. Unexpectedly, as Cidea has heretofore been thought of as a cytoplasmic protein, we detected it in the nucleus and found it to physically interact with transcription factor CCAAT/enhancer-binding protein Î 2 (C/EBPβ) in mammary epithelial cells. We also observed that Cidea induces XOR expression by promoting the association of C/EBPβ onto, and the dissociation of HDAC1 from, the promoter of the Xdh gene encoding XOR. Finally, we found that Fsp27, another CIDE family protein, is detected in the nucleus and interacts with C/EBPβ to regulate expression of a subset of C/EBPβ downstream genes in adipocytes. Thus, Cidea acts as a previously unknown transcriptional coactivator of C/EBPβ in mammary glands to control lipid secretion and pup survival. © 2012 Nature America, Inc. All rights reserved.


Idiopathic pulmonary fibrosis (IPF) is a lethal human disease with short survival time and few treatment options. Herein, we demonstrated that discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase that predominantly transduces signals from fibrillar collagens, plays a critical role in the induction of fibrosis and angiogenesis in the lung. In vitro cell studies showed that DDR2 can synergize the actions of both transforming growth factor (TGF)-β and fibrillar collagen to stimulate lung fibroblasts to undergo myofibroblastic changes and vascular endothelial growth factor (VEGF) expression. In addition, we confirmed that late treatment of the injured mice with specific siRNA against DDR2 or its kinase inhibitor exhibited therapeutic efficacy against lung fibrosis. Thus, this study not only elucidated novel mechanisms by which DDR2 controls the development of pulmonary fibrosis, but also provided candidate target for the intervention of this stubborn disease.Molecular Therapy (2016); doi:10.1038/mt.2016.109. © 2016 American Society of Gene & Cell Therapy


Li B.,PLA Fourth Military Medical University
Cell Death and Differentiation | Year: 2016

The association between inflammation and endoplasmic reticulum (ER) stress has been described in many diseases. However, if and how chronic inflammation governs the unfolded protein response (UPR) and promotes ER homeostasis of chronic inflammatory disease remains elusive. In this study, chronic inflammation resulted in ER stress in mesenchymal stem cells in the setting of periodontitis. Long-term proinflammatory cytokines induced prolonged ER stress and decreased the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Interestingly, we showed that chronic inflammation decreases the expression of lysine acetyltransferase 6B (KAT6B, also called MORF), a histone acetyltransferase, and causes the upregulation of a key UPR sensor, PERK, which lead to the persistent activation of the UPR in PDLSCs. Furthermore, we found that the activation of UPR mediated by MORF in chronic inflammation contributes to the PERK-related deterioration of the osteogenic differentiation of PDLSCs both in vivo and in vitro. Taken together, our results suggest that chronic inflammation compromises UPR function through MORF-mediated-PERK transcription, which is a previously unrecognized mechanism that contributes to impaired ER function, prolonged ER stress and defective osteogenic differentiation of PDLSCs in periodontitis.Cell Death and Differentiation advance online publication, 22 July 2016; doi:10.1038/cdd.2016.74. © 2016 Macmillan Publishers Limited


Luo C.,PLA Fourth Military Medical University | Kuner T.,University of Heidelberg | Kuner R.,University of Heidelberg
Trends in Neurosciences | Year: 2014

Chronic pain represents a major challenge to clinical practice and basic science. Excitatory neurotransmission in somatosensory nociceptive pathways is predominantly mediated by glutamatergic synapses. A key feature of these synapses is their ability to adapt synaptic strength in an activity-dependent manner. Such disease-induced synaptic plasticity is paramount to alterations in synaptic function and structure. Recent work has recognized that synaptic plasticity at both excitatory and inhibitory synapses can function as a prime mechanism underlying pathological pain. In this review, cellular and molecular mechanisms underlying synaptic plasticity in nociceptive pathways will be reviewed and discussed. New insights derived from these advances are expected to expedite development of novel interventional approaches for treatment of pathological pain. © 2014 Elsevier Ltd.


Liu L.,PLA Fourth Military Medical University
International heart journal | Year: 2012

Atrial fibrillation (AF) is a common disease with a poorly understood pathophysiological mechanism. Increasing evidence indicates that AF may be associated with immunologic inflammation responses, but it remains unclear whether activation of peripheral blood CD3(+) T-lymphocytes plays a role in the pathogenesis of AF. The aim of this study was to evaluate this phenomenon. Fifty paroxysmal AF patients and 56 persistent AF patients who underwent successful electrical cardioversion were enrolled. The percentages of CD69 and human leukocyte antigen DR (HLA-DR) positive peripheral blood CD3(+) T-lymphocytes, which indicate T-lymphocyte activation, were examined by flow cytometric analysis in the patients and 51 healthy controls. The patient groups had higher levels of CD69 and HLA-DR than the healthy controls. During the 3-month follow-up, 37 patients had recurrence of AF (recurrence group) and 50 patients remained in sinus (sinus group). The CD69 and HLA-DR levels in the sinus group were all significantly down-regulated at follow-up compared with before cardioversion. However, there were no statistically significant differences between the CD69 and HLA-DR levels in the recurrence group at follow-up and before cardioversion. Our findings suggest that activation of peripheral blood CD3(+) T-lymphocytes was associated with AF, and might be a diagnostic or therapeutic marker.


Pan W.,Xian Physical Education University | Wei Y.,Xian Physical Education University | Zhou L.,Xian Physical Education University | Li D.,PLA Fourth Military Medical University
Journal of Orthopaedic Research | Year: 2011

This study was to compare effect of osteointegration of grafted tendon in bone tunnels between injected calcium phosphate cement (ICPC) and injected fibrin sealant (IFS) combined with bone morphogenetic protein (BMP) after anterior cruciate ligament (ACL) reconstruction. ACL reconstruction was performed bilaterally in 51 rabbits. ICPC-BMP composite was injected into one knee, with the contralateral knee IFS-BMP composite. The rabbits were killed at postoperative weeks 2, 6, and 12 for testing. Histological observations showed the ICPC composite gradually increased the new bone formation during the whole healing process, while the IFS composite had a burst effect on enhancing the healing of tendon-to-bone at 2 and 6 weeks. By 12 weeks, there was more new cartilage and new bone in the interface in the ICPC-bBMP group. Micro-CT showed that the values of BMD in the ICPC-bBMP group were lower than those in the IFS-bBMP group at 6 weeks, while the values in the ICPC-bBMP group were higher than those in the IFS-bBMP group at 12 weeks (p > 0.05). Fluorescent labels showed that the rate of new bone formation of IFS-BMP composite was significantly higher than that of ICPC composite at 6 weeks (3.45±0.62 μm/day vs. 2.93±0.51 μm/day), but the rate was decreased compared with ICPC composite at 12 weeks (2.58±0.72 μm/day vs. 3.05±0.68 μm/day; p < 0.05). Biomechanically, the ultimate failure load in the ICPC-BMP group was always higher than that in the IFS-BMP group. It is evident that the ICPC composite achieved a more prolonged osteogenic effect than that by IFS composite. © 2011 Orthopaedic Research Society Published by Wiley Periodicals.


Wang G.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2013

To investigate the expression levels of enhancer of zeste homolog 2 (EZH2) and human runt-related transcription factor 3 (RUNX3) in renal cell carcinoma (RCC), and analyze their clinical significance and expression correlation. Expressions of EZH2 and RUNX3 proteins were analyzed by immunohistochemistry in 56 RCC tissues and corresponding adjacent normal renal tissues, respectively. Statistic analysis was conducted using SPSS17.0 software. Immunohistochemistry revealed that the positive rates of EZH2 and RUNX3 expressions were 67.9% and 37.5% in RCC tissues, respectively, and they were 28.6% and 67.3% in adjacent normal renal tissues. The expressions of EZHZ and RUNX3 between RCC and normal renal tissues were significantly different (P<0.05). High expression of EZH2 and low expression of RUNX3 in RCC were associated with the clinical stage (P<0.05), but not associated with pathological differentiation, age or gender (P>0.05). No statistically significant negative correlation was observed in the expressions of EZH2 and RUNX3 in RCC (P>0.05). Both EZH2 and RUNX3 may play important roles in the development and progression of RCC, and the detection on EZH2 and RUNX3 expressions will be helpful for early diagnosis and prognosis prediction of RCC.


Pan L.,Shanghai JiaoTong University | He M.,Shanghai JiaoTong University | Ma J.,Shanghai JiaoTong University | Tang W.,East China University of Science and Technology | And 4 more authors.
Theranostics | Year: 2013

Upconversion nanocrystals with small size and strong fluorescent signals own great potential in applications such as biomolecule-labeling, in vivo tracking and molecular imaging. Herein we reported that NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals with small size and strong fluorescent signals were controllably synthesized by oleic acid (OA)/ ionic liquid (IL) two-phase system for targeted fluorescent imaging of gastric cancer in vivo. The optimal synthesis condition of NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals by OA/IL two-phase system was established, adding more metal ion such as Na+ ion could facilitate the size control and crystal-phase transition, more importantly, markedly enhancing fluorescent intensity of beta-phase nanocrystals compared with traditional methods. Alpha-phase NaYbF4, 2%Tm upconversion nanocrystals with less than 10nm in diameter and beta-phase NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals with 30 nm or so in diameter and strong fluorescent signals were obtained, these synthesized nanocrystals exhibited very low cytotoxicity. Folic acid-conjugated silica-modified beta-phase NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals were prepared, could actively target gastric cancer tissues implanted into nude mice in vivo, and realized targeted fluorescent imaging. Folic acid-conjugated silica-modified NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals show great potential in applications such as targeted near infared radiation fluorescent imaging, magnetic resonance imaging and targeted therapy of gastric cancer in the near future. © Ivyspring International Publisher.


Zhao W.,Chinese PLA General Hospital | Bao P.,Chinese PLA General Hospital | Qi H.,PLA Fourth Military Medical University | You H.,North Sichuan Medical College
Oncology Reports | Year: 2010

We studied the effect of resveratrol treatment on multidrug-resistant human non-small cell lung cancer cells. Human multidrug-resistant SPC-A-1/CDDP cells were treated with resveratrol at a concentration of 25, 50, or 100 μM in in vitro studies and nude mice were implanted with multidrug-resistant SPC-A-1/and fed a special diet that included resveratrol at a dose of either 1 g/kg/day or 3 g/kg/ day in in vivo studies. No adverse toxicological effects of resveratrol treatment were observed. The rate of cell proliferation, apoptosis ratio, cell cycle phase distribution, IC 50values of cisplatin, gefitinib, and paclitaxel, implanted tumour volume, and expression of survivin in resveratrol-treated and control mice were then determined. Resveratrol significantly inhibited the proliferation of SPC-A-1/CDDP cells, induced apoptosis, arrested the cell cycle phase between G 0-G 1 and S phase or at the G 2/M phase, decreased the IC 50 values of multiple chemotherapeutic drugs, and showed anti-tumour effects in nude mice that had been implanted with SPC-A-1/ CDDP cells. In additional, resveratrol affected the proliferation of SPC-A-1/CDDP cells in a dose- and time-dependent manner. Expression of survivin in SPC-A-1/CDDP cells decreased after they were treated with all concentrations of resveratrol and resveratrol was also found to have a dose-dependent effect on survivin expression. Resveratrol can induce apoptosis in multidrug-resistant human NSCLC SPC-A-1/ CDDP cells by down-regulating the expression of survivin.


Zheng G.,PLA Fourth Military Medical University
Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology | Year: 2011

To study the effect of chronic multiple stress on learning and memory, and the expression and activation of cerebral extracellular signal-regulated protein kinase (ERK) 1/2 of rats in vivo. Ninety male SD rats were divided randomly into control group and stress group. Rats in stress group were stressed everyday by one of the seven stressors including cold exposure, foot shock, white noise, restraint, tail hung up, sleep deprivation, and level shake, and then the ability of learning and memory was determined by Morris water maze test. Serum corticosterone (CORT) level was determined by radioimmunoassay kit. Western blot was performed to determine the expression and phosphorylation of ERK in hippocampus and prefrontal cortex of the brain. The escape latencies of stressed rats were substantially longer than those of the controls in the water maze test (P < 0.01) except a transient recovery at the end of the third week after the stress. The stress also resulted in significantly higher serum CORT level and decreased P-ERK level in hippocampus and prefrontal cortex (PFC) (P < 0.01). Similarly, transient elevation of both CORT and P-ERK levels were observed at the end of the third week. Chronic multiple stress can lead to impaired learning and memory by decreasing the phosphorylation of ERK in the hippocampus and PFC. The partial recovery of learning and memory, CORT and P-ERK levels at the end of the third week may due to the adaptation of the rats to stressors.


Yang X.,Shaanxi Normal University | Lv Y.,Shaanxi Normal University | Lv Y.,Lund University | Tian L.,Shaanxi Normal University | Zhao Y.,PLA Fourth Military Medical University
Journal of Agricultural and Food Chemistry | Year: 2010

This study was undertaken to characterize the water-soluble polysaccharides isolated from an herbal tea, the leaves of L. lucidus Turcz. HPLC analysis showed that L. lucidus polysaccharides (LLPs) were mainly composed of galactose (50.1 mol %), followed by galacturonic acid (14.2 mol %), accounting for 64.3 mol % of all quantitative nine monosaccharides. Furthermore, we evaluated the systemic immunological efficacy of LLPs in mice. Mice were intragastrically administered once daily with low-dose (50 mg/kg), intermediate-dose (100 mg/kg), and high-dose (300 mg/kg) of LLPs, respectively, for 30 consecutive days. In comparison with vehicle, LLPs significantly enhanced the plaque-forming cells (PFCs), and serum hemolysin level, and delayed-type hypersensitivity (DTH) in response to sheep red blood cells (SRBC) in a dose-dependent manner (p < 0.01). In LLPs-treated mice, phagocytosis capacity and concanavalin A-induced spleenocyte proliferation were remarkably increased (p < 0.05). The intermediate- and high-dose of LLPs also caused a significant increase in the indices of thymus and spleen organs of mice (p < 0.05). This suggests that the polysaccharides derived from the tea leaves of L. lucidus improves the immune system and might be regarded as a biological response modifier. © 2010 American Chemical Society.


Chen W.,Solvias AG | Chen W.,PLA Fourth Military Medical University | Spindler F.,Solvias AG | Pugin B.,Solvias AG | Nettekoven U.,Solvias AG
Angewandte Chemie - International Edition | Year: 2013

These cats are purrfectionists: The ChenPhos ligands (see structure) showed dramatically higher catalytic activity in the title reaction than their C 2-symmetric predecessor with two dimethylaminoethyl-substituted ferrocenyl(phenyl)phosphanyl groups. The ready accessibility, extreme air stability, and high enantioselectivity, activity, and productivity of these ligands make them very promising for a wide range of practical applications. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Zhang Y.,University of Pennsylvania | Li S.,University of Pennsylvania | Yuan L.,University of Pennsylvania | Yuan L.,PLA Fourth Military Medical University | And 6 more authors.
Genes and Development | Year: 2010

Cardiomyocyte proliferation is high in early development and decreases progressively with gestation, resulting in the lack of a robust cardiomyocyte proliferative response in the adult heart after injury. Little is understood about how both cell-autonomous and nonautonomous signals are integrated to regulate the balance of cardiomyocyte proliferation during development. In this study, we show that a single transcription factor, Foxp1, can control the balance of cardiomyocyte proliferation during development by targeting different pathways in the endocardium and myocardium. Endocardial loss of Foxp1 results in decreased Fgf3/Fgf16/Fgf17/Fgf20 expression in the heart, leading to reduced cardiomyocyte proliferation. This loss of myocardial proliferation can be rescued by exogenous Fgf20, and is mediated, in part, by Foxp1 repression of Sox17. In contrast, myocardial-specific loss of Foxp1 results in increased cardiomyocyte proliferation and decreased differentiation, leading to increased myocardial mass and neonatal demise. We show that Nkx2.5 is a direct target of Foxp1 repression, and Nkx2.5 expression is increased in Foxp1-deficient myocardium. Moreover, transgenic overexpression of Nkx2.5 leads to increased cardiomyocyte proliferation and increased ventricular mass, similar to the myocardial-specific loss of Foxp1. These data show that Foxp1 coordinates the balance of cardiomyocyte proliferation and differentiation through cell lineage-specific regulation of Fgf ligand and Nkx2.5 expression. © 2010 by Cold Spring Harbor Laboratory Press.


Zhang H.,Shaanxi Normal University | Zhang M.,Shaanxi Normal University | Yu L.,Shaanxi Normal University | Zhao Y.,PLA Fourth Military Medical University | And 2 more authors.
Food and Chemical Toxicology | Year: 2012

This study is designed to compare the anticancer effects of quercetin and its water-soluble sulfated derivative, quercetin-5',8-disulfonate (QS), in human colon cancer LoVo cells and breast cancer MCF-7 cells. It was found that both quercetin and QS can inhibit the growth of cancer cells in a dose-dependent manner, with the IC 50 values of 40.2 and 28.0μM for LoVo cells and 30.8 and 19.9μM for MCF-7 cells, respectively, suggesting QS was more effective against the cancer cells than quercetin. Moreover, flow cytometric assay revealed that quercetin and QS could mediate the cell-cycle arrest principally in the S phase after 24h of treatment with the two tumor cells. It was also found that 69.6% of LoVo cells and 90.6% of MCF-7 cells entered the early phase of apoptosis when treated with 100μM QS for 48h. Furthermore, we firstly found the generation of ROS is a critical mediator in QS-induced cell growth inhibition. Taken together, the novel sulfated derivative of quercetin possesses strong antitumor activity via a ROS-dependent apoptosis pathway, and has the excellent potential to be developed into an antitumor precursor compound. © 2012 Elsevier Ltd.


Baskys A.,Alzheimers Disease Prevention and Treatment Center | Cheng J.-X.,PLA Fourth Military Medical University | Cheng J.-X.,University of California at Los Angeles
Experimental Gerontology | Year: 2012

Vascular dementia (VaD) is a common dementing illness. There are no pharmacological agents with a regulatory approval for its treatment or prevention. Review of published clinical trial reports indicates that early treatment of hypertension, a risk factor for stroke, reduces VaD risk and slows progression. However, unlike stroke, treatment of hyperlipidemia with statin class drugs or treatment of blood clotting abnormalities with acetylsalicylic acid do not appear to have an effect on VaD incidence or progression. Pharmacological agents for treatment of Alzheimer's dementia (AD) such as memantine or acetylcholinesterase inhibitors have small positive effects on cognition in VaD, which are likely due to their action on co-existing AD-related neuropathology. Drug development efforts using novel approaches such as patient stratification by their genotype are needed in order to address the increasing need for effective VaD therapeutics. © 2012 Elsevier Inc.


Tian Y.,University of Pennsylvania | Yuan L.,University of Pennsylvania | Yuan L.,PLA Fourth Military Medical University | Goss A.M.,University of Pennsylvania | And 8 more authors.
Developmental Cell | Year: 2010

Little is understood about the molecular mechanisms underlying the morphogenesis of the posterior pole of the heart. Here we show that Wnt2 is expressed specifically in the developing inflow tract mesoderm, which generates portions of the atria and atrio-ventricular canal. Loss of Wnt2 results in defective development of the posterior pole of the heart, resulting in a phenotype resembling the human congenital heart syndrome complete common atrio-ventricular canal. The number and proliferation of posterior second heart field progenitors is reduced in Wnt2-/- mutants. Moreover, these defects can be rescued in a temporally restricted manner through pharmacological inhibition of Gsk-3β. We also show that Wnt2 works in a feedforward transcriptional loop with Gata6 to regulate posterior cardiac development. These data reveal a molecular pathway regulating the posterior cardiac mesoderm and demonstrate that cardiovascular defects caused by loss of Wnt signaling can be rescued pharmacologically in vivo. © 2010 Elsevier Inc. All rights reserved.


Zang Y.,PLA Fourth Military Medical University
Menopause | Year: 2016

OBJECTIVE:: Osteoporosis and hypertension are age-related chronic diseases with increased morbidity rates among postmenopausal women. Clinical epidemiological investigations have demonstrated that hypertensive patients treated with β1-selective β-blockers have a higher bone mineral density (BMD) and lower fracture risk. Nevertheless, no fundamental studies have examined the relationships between β1-selective β-blockers and these effects. The present study explored the effects and mechanisms of metoprolol in the in vitro treatment of osteoblasts and the in vivo treatment of ovariectomy-induced osteoporosis in rats. METHODS:: Primary osteoblasts were obtained by digestion of the cranial bones of 24-hour-old Sprague-Dawley rats. After metoprolol treatment, cell proliferation and differentiation capacities were assessed at the corresponding time points. In addition, 3-month-old female Sprague-Dawley rats (200-220?g) were divided into a sham-operated group (n?=?8) and three ovariectomized (OVX) (bilateral removal of ovaries) groups as follows: vehicle (OVX; n?=?8), low-dose metoprolol (L-M, oral, 120?mg/kg/d; n?=?8), and high-dose metoprolol (H-M, oral, 240?mg/kg/d; n?=?8). After 12 weeks of metoprolol treatment, BMD, microarchitecture, and biomechanical properties were evaluated. RESULTS:: The results indicated that the treatments with 0.01 to 0.1?μM metoprolol increased osteoblast proliferation, alkaline phosphatase activity, and calcium mineralization, and promoted the expression of osteogenic genes. The in vivo study indicated that administration of metoprolol to OVX rats resulted in maintenance of the BMDs of the L4 vertebrae. Moreover, amelioration of trabecular microarchitecture deterioration and preservation of bone biomechanical properties were detected in the trabecular bones of the OVX rats. CONCLUSIONS:: Our findings indicate that metoprolol prevents estrogen deficiency-induced bone loss by increasing the number and enhancing the biological functions of osteoblasts, implying its potential use as an alternative treatment for postmenopausal osteoporosis in hypertensive patients. © 2016 by The North American Menopause Society.


Liang J.,PLA Fourth Military Medical University
Journal of gastroenterology | Year: 2011

Recent studies proved that inflammatory bowel disease (IBD) patients had a higher risk of thromboembolism and a Factor V Leiden mutation that prevents the efficient inactivation of factor V, which leads to thromboembolism and thus contributes to a high potential risk of IBD. However, the relationship between Factor V Leiden mutation and IBD remains controversial. We conducted a systematic review with meta-analysis of studies assessing the association of Factor V Leiden mutation with the risk of IBD in humans. We extracted the number of IBD and control subjects with or without Factor V Leiden mutation from each study and conducted this analysis using a fixed-effects model. Nineteen studies met the inclusion criteria and were included in the meta-analysis. No significant heterogeneity was found in results across the 19 studies (I (2) = 18.8%, P = 0.23), which showed a slight but not significant increase in the risk of IBD with Factor V Leiden mutation in the general population (summary odds ratio [OR] 1.13, 95% confidence interval [CI] 0.87-1.46). Taking into account ethnic differences, further study exhibited a slight but not significant increase in risk of IBD with Factor V Leiden mutation in Europeans (summary OR 1.20, 95% CI 0.88-1.64). However, Factor V Leiden mutation was significantly associated with a higher risk of thromboembolism in IBD patients (summary OR 5.30, 95% CI 2.25-12.48). No publication bias was found in this study. This meta-analysis indicated that although Factor V Leiden mutation was not significantly associated with the risk of IBD, it was significantly associated with a higher risk of thromboembolism in IBD patients.


Wu X.,PLA Fourth Military Medical University
Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi | Year: 2010

This research was carried out to investigate the effect of basic fibrous growth factor (bFGF) controlled release hydrogel nanoparticles on the proliferation and differentiation of mesenchymal stem cells. The dex-GMA-bFGF-NPs were prepared by an improved emulsion polymerization method; their morphology, size and encapsulated ratio were assessed by routine procedure. Dynamic dialysis method was used to determine the release characteristics of dex-GMA-bFGF-NPs in vitro. The secondary culture MSCs were divided into four groups according the different ingredients being added into the DMEM culture medium: free bFGF group (A), blank dex-GMA nanoparticles group (B), dex-GMA-bFGF nanoparticles group (C), nothing group (D). The proliferation of cultured MSCs was measured by using cell counting method, MTT method and flow cytometry. ALP kit was used to evaluate the ALP activity of the MSCs to show the differentiation of the cells by adding the dex-GMA-bFGF-NPs to the DMEM culture medium (C group) or bFGF only (A group). B group and D group were taken as the controls. The results were analyzed by statistical analysis software (SPSS11.0). All results showed that the shape of dex-GMA-bFGF-NPs was spherical. The encapsulated ratio was 88% and more than 85% of the encapsulated bFGF could be released during 14 days. The in vitro cellular study showed the control release of bFGF from nanoparticles could promote the proliferation of MSCs. After 12 days, the cell number in groups A, B and C was (21.97 +/- 0.25) x 10(4) cells/ml, (12.43 +/- 0.13) x 10(4) cells/ml, (27.45 +/- 0.78) x 10(4) cells/ml and (12.03 +/- 0.43) x 10(4) cells/ml, with the difference being statistically significant among them (P < 0.05). The flow cytometry revealed that the G2/M+S percentage in group C was the highest at 4-8 days after plate culture(P < 0.05). During the first 3 days, the proliferation and differentiation of BMSCs between group A and group B were of no significance (P > 0.05), but were much faster than those of group C and D. After 7 days, dex-GMA-bFGF-NPs could enhance BMSCs proliferation and differentiation continually, but bFGF had no enhancement any more, the difference between group A and group B became more significant (P < 0.05). So we made the conclusions the bFGF loading dex-GMA hydrogel nanoparticles can release bFGF more than 21 days and can promote the proliferation and differentiation of the BMSCs through a long period of controlled release of bFGF. Dex-GMA-bFGF-NPs may be an ideal controlled release carrier for bioactive growth factors.


Mi Y.-J.,Shanghai JiaoTong University | Hou B.,Beijing Institute of Radiation Medicine | Liao Q.-M.,Shanghai JiaoTong University | Ma Y.,Shanghai JiaoTong University | And 5 more authors.
Cell Death and Differentiation | Year: 2012

Nogo-A is originally identified as an inhibitor of axon regeneration from the CNS myelin. Nogo-A is mainly expressed by oligodendrocytes, and also by some neuronal subpopulations, particularly in the developing nervous system. Although extensive studies have uncovered regulatory roles of Nogo-A in neurite outgrowth inhibition, precursor migration, neuronal homeostasis, plasticity and neurodegeneration, its cell-autonomous functions in neurons are largely uncharacterized. Here, we show that HIV-1 trans-activating-mediated amino-Nogo-A protein transduction into cultured primary cortical neurons achieves an almost complete neuroprotection against oxidative stress induced by exogenous hydrogen peroxide (H 2O 2). Endogenously expressed neuronal Nogo-A is significantly downregulated upon H 2O 2 treatment. Furthermore, knockdown of Nogo-A results in more susceptibility to acute oxidative insults and markedly increases neuronal death. Interacting with peroxiredoxin 2 (Prdx2), amino-Nogo-A reduces reactive oxygen species (ROS) generation and extracellular signal-regulated kinase phosphorylation to exert neuroprotective effects. Structure-function mapping experiments reveal that, out of NiG-Δ20, a novel region comprising residues 290-562 of amino-Nogo-A is indispensable for preventing oxidative neuronal death. Moreover, mutagenesis analysis confirms that cysteine residues 424, 464 and 559 are involved in the inhibition of ROS generation and neuroprotective role of amino-Nogo-A. Our data suggest that neuronal Nogo-A might play a cell-autonomous role in improving neuronal survival against oxidative insult through interacting with Prdx2 and scavenging of ROS. © 2012 Macmillan Publishers Limited All rights reserved.


Li W.-L.,PLA Fourth Military Medical University | Pauluhn J.,Bayer AG
Toxicology | Year: 2010

Young adult male Wistar rats, a species commonly used in inhalation toxicity studies, and OF1 mice, a species often used in sensory irritation studies, were simultaneously nose-only exposed for 45-min to ammonia in concentrations from 92 to 1243mg/m3. This study examined airway reflexes by the changes in respiratory patterns elicited by ammonia in either dry, steam-humidified (approximately 95% relative humidity) or aqueous aerosol containing atmospheres. This served the objective to explore whether high concentrations of anhydrous ammonia and/or high humidity and aqueous aerosol change the predominant nasal deposition site to more distal locations in the lung. Animals from all groups tolerated the exposure without evidence of respiratory tract irritation, changes in body and lung weights. The evoked changes on breathing patterns resembled those known to occur following exposure to 'upper respiratory tract sensory irritants', rapid in onset and reversibility. Reflex stimulation from the lower airways was not observed in any group. While mice showed some adaption during the 45-min exposure period, rats displayed more stable changes in respiratory patterns. In this species humidity- or aqueous aerosol-related changes in sensory irritation potency did not occur to any appreciable extent. The respiratory decrease 50%, RD50, was 972 and 905mg/m3 in dry and wet air, respectively. In contrast, mice appeared to more susceptible to ammonia in presence of dry air (the RD50, was 582 and 732mg/m3 in dry and wet air, respectively). In summary, it was shown that the sensory irritation potency of ammonia does not increase when inhaling wet atmospheres nor penetrates this gas into the lower airways up to 1243mg/m3×45-min. The mild-to-moderate sensory irritation-related effects observed at ≈400mg/m3 (571ppm)×45-min do not appear to be offensive enough to impair escape as a result of upper airway sensations. Interestingly, this rat-based estimate matches almost exactly the experienced-based RAM TRAC recommendations of 696 and 492ppm for 30 and 60min, respectively. © 2010 Elsevier Ireland Ltd.


Wang L.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2010

AIM: To observe the difference in the expression of glucagon in normal and in diet-induced hyperlipidemic gestational rats. METHODS: Thirty-two female SD rats were divided into control group, hyperlipidemia group, gestation group and hyperlipidemic-gestation group. Fourteen days after gestation, real-time quantitative PCR was performed to detect the expression of preglucagon mRNA and Western blot was employed to detect the expression of glucagon in pancreas in different groups. RESULTS: The glucose peak of OGTT was 30 minutes after glucose load in all the rats. The insulin peak of OGTT was 15 minutes after glucose load in controls, while the insulin peak was 30 minutes after glucose load in other groups. Fasting insulin in both gestation rats and hyperlipidemic-gestation rats was higher than that in controls(21.68+/-2.55 vs 14.35+/-0.86 mIU/L, P<0.05; 25.76+/-3.31 vs 14.35+/-0.86 mIU/L, P<0.01). Insulin AUC in both hyperlipidemic-gestation rats and hyperlipidemia rats was also higher than that in controls(204.60+/-79.06 vs 129.71+/-11.33 mIU/L, P<0.05; 230.25+/-13.19 vs 129.71+/-11.33 mIU/L, P<0.05). PG relative mRNA levels in gestation rats and in hyperlipidemic-gestation rats were respectively 1.46 fold and 1.77 fold higher than that in controls (P<0.05 and P<0.01)and 1.54 fold higher than that in hyperlipidemia rats (P=0.01). Glucagon in gestation rats and hyperlipidemic-gestation rats was respectively 2.57 fold and 3.44 fold higher than that in controls (both P<0.01)and 2.9 fold higher than that in hyperlipidemia rats(P<0.01). CONCLUSION: Both hyperlipidemia and gestation may delay the releasing peak of insulin after glucose load. In normal gestation it is mainly reflected by fasting insulin resistance and in hyperlipidemic-gestation it is reflected by both fasting and glucose load insulin resistance. The rising pancreatic glucagons may partly lead to the increased gestational insulin resistance.


Wei B.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2010

AIM: To observe the expression of nuclear factor-kappaB (NF-kappaB) and glucose transporter-4 (GLUT-4) in uteru of rats with gestational diabetes mellitus (GDM) and to explore the relationship between inhibition of NF-kappaB and insulin resistance. METHODS: Thirty Sprague-Dawley rats were randomly divided into 3 groups: normal pregnant control (NC) group, GDM group and PDTC group, 10 rats each group. GDM rat model was established by intraperitoneal (ip) injection of streptozotocin (STZ). PDTC (40 mg/kg) was ip injected in PDTC group.The rats were sacrificed on the 20-day of pregnancy before delivery. The uterus were taken to observe the pathological changes. The expressions of GLUT-4 and NF-kappaB in uteru tissue were detected by immunohistochemical staining and Western blot. RESULTS: The renal NF-kappaB activity in GDM group was higher significantly than that in NC group (P<0.01); and NF-kappaB activity in PDTC group was lower than that in GDM group (P<0.01). The expression of GLUT-4 in GDM group was significantly lower than that in NC group (P<0.01). However, compared with GDM group, the expression of GLUT-4 in PDTC group was increased (P<0.01). CONCLUSION: The inhibition of NF-kappaB activity can increase the expression of GLUT-4 in uterus of GDM rats, indicating that the occurrence of GDM in rats with uteru insulin resistance may be related with the intervention of NF-kappaB activity on the down regulation of the expression of GLUT-4.


Shang L.,PLA Fourth Military Medical University | O'Loughlin J.,University of Montreal | Tremblay A.,Laval University | Gray-Donald K.,McGill University
Applied Physiology, Nutrition and Metabolism | Year: 2014

Identifying food patterns related to obesity can provide information for health promotion in nutrition. Food patterns and their relation with obesity among Canadian children have not been reported to date. Our aim was to identify and describe food patterns associated with obesity in children at risk of overweight. Caucasian children (n = 630) with at least 1 obese biological parent recruited into the Quebec Adiposity and Lifestyle Investigation in Youth (QUALITY) cohort were studied in cross-sectional analyses. Measures of adiposity (body mass index (BMI), waist circumference, body fat mass percentage measured by dual-energy X-ray absorptiometry), screen time, physical activity (accelerometer over 7 days), and dietary intake (three 24-h food recalls) were collected. Factor analysis was used to identify food patterns. The relationships between food patterns and overweight were investigated in logistic and multiple linear regression models. Three food patterns were retained for analysis: traditional food (red meats, main dishes-soups, high-fat dairy products, tomato products, dressings, etc.); healthy food (low-fat dairy products, whole grains, legumes-nuts-seeds, fruits, vegetables); and fast food (sugar-sweetened beverages, fried potatoes, fried chicken, hamburgers-hot dogs-pizza, salty snacks). Higher scores on the fast food pattern were associated with overweight (BMI ≥ 85th percentile), and other measures of adiposity (BMI, waist circumference, body fat mass percentage) after adjustment for age, sex, physical activity, screen time, sleep time, family income, and mother's obesity (p < 0.05). Controlling for energy intake did not change these relationships. Our results provide further evidence of a link between fast food intake and obesity in children.


He N.-W.,Shaanxi Normal University | Zhao Y.,PLA Fourth Military Medical University | Guo L.,Shaanxi Normal University | Shang J.,Shaanxi Normal University | Yang X.-B.,Shaanxi Normal University
Journal of Medicinal Food | Year: 2012

Dietary and medicinal uses of Panax notoginseng have been associated with reduced risk of cancer. This study was designed to investigate the profiles of P. notoginseng saponin extract (PNSE), the major bioactive ingredients in P. notoginseng (Burk.) F.H. Chen, by high-performance liquid chromatography, and, for the first time, the anticancer effect of PNSE in the human colon cancer cell line LoVo was further evaluated. The major saponins present in PNSE were ginsenosides Rg1 (31.1%) and Rb1 (34.4%), and the total content of the eight saponins identified (notoginsenoside R1, ginsenosides Rg1, Re, Rb1, Rc, and Rd, and isomeric ginsenosides Rb2 and Rb3) was 81.7%, indicating that it was a highly purified standardized saponin extract. Furthermore, PNSE was found to have a markedly cytotoxic effect and antiproliferative activity against the LoVo cell line in a dose- and time-dependent manner. Flow cytometry analysis demonstrated that PNSE caused cell cycle arrest at S phase. Moreover, PNSE was found to possess antioxidative capacities in the 1,1-diphenyl-2-picrylhydrazyl free radical scavenging assay and hydroxyl radical scavenging assay in vitro. Taken together, the present results suggest that naturally occurring PNSE may provide significant natural defense against human colon cancer. © Copyright 2012, Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition.


He N.,Shaanxi Normal University | Yang X.,Shaanxi Normal University | Jiao Y.,Shaanxi Normal University | Tian L.,Wageningen University | Zhao Y.,PLA Fourth Military Medical University
Food Chemistry | Year: 2012

Wolfberry fruit polysaccharides (WFPs) were isolated by hot-water extraction and ethanol precipitation. With HPLC analysis, WFPs were for the first time identified as acidic polysaccharides with galacturonic acid being the main component monosaccharide (24.9%), followed by galactose (21.3%), arabinose (18.5%), and glucose (15.9%), accounting for up to 80.6% of the molar percentage. WFPs exhibited a high antioxidant activity and a dose-dependent antiproliferative effect, with IC 50 values of 134.9, 70.1 and 138.4 μg/mL against A549, MCF-7 and LoVo cancer cells after 48 h of incubation as estimated by MTT assay, respectively. Flow cytometry analysis showed that WFPs exerted a stimulatory effect on apoptosis of MCF-7 cells, and induced the cell-cycle arrest at the G0/G1 phase, with the observation of intracellular ROS production and DNA damage. The present study demonstrated that these polysaccharides might have the potential to provide significant natural defence against human cancer. © 2012 Elsevier Ltd. All rights reserved.


Chen F.M.,PLA Fourth Military Medical University
Tissue engineering. Part B, Reviews | Year: 2010

The management of periodontal tissue defects that result from periodontitis represents a medical and socioeconomic challenge. Concerted efforts have been and still are being made to accelerate and augment periodontal tissue and bone regeneration, including a range of regenerative surgical procedures, the development of a variety of grafting materials, and the use of recombinant growth factors. More recently, tissue-engineering strategies, including new cell- and/or matrix-based dimensions, are also being developed, analyzed, and employed for periodontal regenerative therapies. Tissue engineering in periodontology applies the principles of engineering and life sciences toward the development of biological techniques that can restore lost alveolar bone, periodontal ligament, and root cementum. It is based on an understanding of the role of periodontal formation and aims to grow new functional tissues rather than to build new replacements of periodontium. Although tissue engineering has merged to create more opportunities for predictable and optimal periodontal tissue regeneration, the technique and design for preclinical and clinical studies remain in their early stages. To date, the reconstruction of small- to moderate-sized periodontal bone defects using engineered cell-scaffold constructs is technically feasible, and some of the currently developed concepts may represent alternatives for certain ideal clinical scenarios. However, the predictable reconstruction of the normal structure and functionality of a tooth-supporting apparatus remains challenging. This review summarizes current regenerative procedures for periodontal healing and regeneration and explores their progress and difficulties in clinical practice, with particular emphasis placed upon current challenges and future possibilities associated with tissue-engineering strategies in periodontal regenerative medicine.


Chen Y.Y.,PLA Fourth Military Medical University
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2011

This study was purposed to optimize the culture conditions of the human amniotic epithelium cells (hAEC) in vitro, and detect the expression of hAEC pluripotent markers. Amnion tissues were separated from the underlying chorion through the spongy layer immediately after elective cesarean section of healthy pregnancy women at term. After the subsequent exposure to trypsin digestion, hAEC were cultured in DMEM with different supplements. The growth and proliferation potential of hAEC was evaluated, and the expression of cultured hAEC pluripotent markers was detected by using flow cytometry and immunohistochemistry methods. The results indicated that when being cultured in the mediums similar to that of embryonic stem cell culture supplemented with 10 ng/ml EGF, the hAEC grew better and the time for passage was shortened. In addition, compared to other culture conditions, under this condition, the cells could be passaged up to 5 times as much without obvious morphological changes, and the pluripotent marker SSEA-4 was detected in the cultured cells by flow cytometry. Meanwhile, the detection of immunofluorescence showed the expression of vimentin in cultured hAEC was strengthened as compared with primary cells. It is concluded that the culture condition similar to that for embryonic stem cells supplemented with EGF facilitates the proliferation and passage of hAEC in vitro.


Chu C.,Chinese PLA General Hospital | Xu B.,Chinese PLA General Hospital | Huang W.,PLA Fourth Military Medical University
Journal of Molecular Histology | Year: 2010

The expression and new functions of reproductive hormones in organs beyond hypothalamus-pituitary-gonad axis have been reported. So far, there is no report about the protective effects of GnRH analogue to hippocampal neurons suffering from ischemia-reperfusion injury. Middle cerebral artery occlusion model together with TUNEL staining were made in vivo and oxygen-glucose deprivation model together with double staining of Annexin V/PI with flow cytometer were made in vitro to observe the anti-apoptotic effects of GnRH analogue to hippocampal neurons after ischemia-reperfusion injury. The results found that the number of TUNEL positive pyramidal neurons in CA1 region in GnRH analogue experiment group was less than that in control group in vivo; the percentage of apoptotic neurons in GnRH analogue experiment group was less than that in control group in vitro. These findings suggested that pretreatment with certain concentration of GnRH analogue could attenuate apoptosis of hippocampal neurons. GnRH analogue has the protective effects to neurons. © 2010 Springer Science+Business Media B.V.


Zhu Y.-S.,University of Texas Southwestern Medical Center | Zhu Y.-S.,PLA Fourth Military Medical University | Tarumi T.,University of Texas Southwestern Medical Center | Tseng B.Y.,University of Texas Southwestern Medical Center | And 3 more authors.
Journal of Cerebral Blood Flow and Metabolism | Year: 2013

Physical activity may influence cerebrovascular function. The objective of this study was to determine the impact of life-long aerobic exercise training on cerebral vasomotor reactivity (CVMR) to changes in end-tidal CO2 (EtCO2) in older adults. Eleven sedentary young (SY, 27±5 years), 10 sedentary elderly (SE, 72±4 years), and 11 Masters athletes (MA, 72±6 years) underwent the measurements of cerebral blood flow velocity (CBFV), arterial blood pressure, and EtCO2 during hypocapnic hyperventilation and hypercapnic rebreathing. Baseline CBFV was lower in SE and MA than in SY while no difference was observed between SE and MA. During hypocapnia, CVMR was lower in SE and MA compared with SY (1.87±0.42 and 1.47±0.21 vs. 2.18±0.28 CBFV%/mm Hg, P<0.05) while being lowest in MA among all groups (P<0.05). In response to hypercapnia, SE and MA exhibited greater CVMR than SY (6.00±0.94 and 6.67±1.09 vs. 3.70±1.08 CBFV1%/mm Hg, P<0.05) while no difference was observed between SE and MA. A negative linear correlation between hypo-and hypercapnic CVMR (R 2 =0.37, P<0.001) was observed across all groups. Advanced age was associated with lower resting CBFV and lower hypocapnic but greater hypercapnic CVMR. However, life-long aerobic exercise training appears to have minimal effects on these age-related differences in cerebral hemodynamics. © 2013 ISCBFM.


Wu H.,Northeastern University | Wu H.,PLA Fourth Military Medical University | Zhu L.,Northeastern University | Torchilin V.P.,Northeastern University
Biomaterials | Year: 2013

To introduce pH sensitivity into the DSPE-PEG-based micellar system and achieve the quick intracellular drug release in response to the acidity in endosomes, a mixed polymeric micelle was developed based on three grafted copolymers, including 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000(DSPE-PEG2000), antinucleosome antibody (mAb 2C5)-modified DSPE-PEG3400 (DSPE-PEG3400-2C5), and poly(ethylene glycol)-coupled poly(l-histidine) (PHIS-PEG2000). The structure of PHIS-PEG2000 was confirmed by 1H NMR spectroscopy. The mixed micelles with the diameter ranging from 110 to 135 nm were prepared using a dialysis method against pH 7.6 PBS. Paclitaxel (PCT) was used as a model drug, the encapsulation efficiency and loading content of PCT were 88% and 5%, respectively. The mixed micelles composed with 50wt% of PHIS-PEG2000 showed the desired pH-dependent drug release property with much faster drug release than micelles without PHIS-PEG2000. At pH around 5.5, about 75-95% of the loaded drug was released within 2 h. The MTT assay showed PCT-loaded mixed micelles had higher cytotoxicity at pH 5.8 than that at pH 7.4. Further modification of the mixed micelles with anti-cancer nucleosome-specific monoclonal antibody 2C5 significantly increased their cellular uptake efficiency and cytotoxicity. Thus, the low pH in endosomes could trigger the PCT release from the pH-sensitive mixed micelles after 2C5-mediated endocytosis. The results of this study suggest that the mixed micelles (DSPE-PEG2000/DSPE-PEG3400-2C5/PHIS-PEG2000) could enhance the tumor cell-specific internalization and trigger the quick drug release, resulting in the improved anti-cancer efficacy. © 2012 Elsevier Ltd.


Shi C.H.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2011

To investisate the inhibition of Hsp-16.3 on the autophagosomes formation of macrophages. Mouse RAW264.7 macrophages were induced by rapamycin (50 ng/μL) following infection with M.tuberculosis H37Rv strains, thereafter, co-incubated with Hsp16.3 protein (25 μg/mL). The effects of Hsp16.3 protein on the autophagosomes formation was observed with transmission electron microscope. The expression of autophagy-related genes (atg8) for macrophages was detected by Western blotting. It was found that rapamycin-induced autophagy of macrophages infected with M.tuberculosis H37Rv enhanced localization of mycobacteria with autophagosomes. Hsp16.3 protein inhibits autophagosome formation and affects M.tuberculosis survival inside infected macrophages. Furthermore, Hsp16.3 protein significantly increased M.tuberculosis colony forming units (CFU), and decreased the expression of microtubule-associated protein light chain-3 (LC3) expression level (P<0.05). The results showed that Hsp16.3 protein inhibits the formation of autophagosomes by regulating the expression of LC3 protein.


Liu Y.,State University of New York at Stony Brook | Liang Z.,State University of New York at Stony Brook | Ma J.,Southern Medical University | Lu H.,PLA Fourth Military Medical University | And 3 more authors.
IEEE Transactions on Medical Imaging | Year: 2014

Previous studies have shown that by minimizing the total variation (TV) of the to-be-estimated image with some data and/or other constraints, a piecewise-smooth X-ray computed tomography image can be reconstructed from sparse-view projection data. However, due to the piecewise constant assumption for the TV model, the reconstructed images are frequently reported to suffer from the blocky or patchy artifacts. To eliminate this drawback, we present a total variation-stokes-projection onto convex sets (TVS-POCS) reconstruction method in this paper. The TVS model is derived by introducing isophote directions for the purpose of recovering possible missing information in the sparse-view data situation. Thus the desired consistencies along both the normal and the tangent directions are preserved in the resulting images. Compared to the previous TV-based image reconstruction algorithms, the preserved consistencies by the TVS-POCS method are expected to generate noticeable gains in terms of eliminating the patchy artifacts and preserving subtle structures. To evaluate the presented TVS-POCS method, both qualitative and quantitative studies were performed using digital phantom, physical phantom and clinical data experiments. The results reveal that the presented method can yield images with several noticeable gains, measured by the universal quality index and the full-width-at-half-maximum merit, as compared to its corresponding TV-based algorithms. In addition, the results further indicate that the TVS-POCS method approaches to the gold standard result of the filtered back-projection reconstruction in the full-view data case as theoretically expected, while most previous iterative methods may fail in the full-view case because of their artificial textures in the results. © 1982-2012 IEEE.


Zhang L.-F.,PLA Fourth Military Medical University | Hargens A.R.,University of California at San Diego
Aviation Space and Environmental Medicine | Year: 2014

Visual imp airment intracranial pressure syndrome (VIIP) is considered a major risk for future human spaceflight. Loss of hydrostatic pressure gradients in vascular and cerebrospinal fluid systems due to the removal of gravity associated with subsequent intracranial and intraocular fluid shifts and the resulting intraocular/intracranial pressure mismatch might be important etiology factors causing VIIP syndrome. Acclimation changes in the ocular and cerebral circulation and the two fluid systems during chronic microgravity exposure and their underlying mechanisms need further elucidation. Relevant findings may help to validate the pressure differential hypothesis for VIIP syndrome and to evaluate whether a gravity based countermeasure is needed. © by the Aerospace Medical Association, Alexandria, VA.


Feng B.,PLA Fourth Military Medical University
Biomedical materials (Bristol, England) | Year: 2011

The purpose of this study was to investigate the role of pore size on tissue ingrowth and neovascularization in porous bioceramics under the accurate control of the pore parameters. For that purpose, β-tricalcium phosphate (β-TCP) cylinders with four different macropore sizes (300-400, 400-500, 500-600 and 600-700 μm) but the same interconnection size (120 μm) and unchangeable porosity were implanted into fascia lumbodorsalis in rabbits. The fibrous tissues and blood vessels formed in scaffolds were observed histologically and histomorphometrically. The vascularization of the porous bioceramics was analyzed by single-photon emission computed tomography (SPECT). It is found that pore size as an important parameter of a porous structure plays an important role in tissue infiltration into porous biomaterial scaffolds. The amount of fibrous tissue ingrowth increases with the decrease of the pore size. In four kinds of scaffolds with different macropore sizes (300-400, 400-500, 500-600 and 600-700 μm) and a constant interconnection size of 120 μm, the areas of fibrous tissue (%) were 60.5%, 52.2%, 41.3% and 37.3%, respectively, representing a significant decrease at 4 weeks (P < 0.01). The pore size of a scaffold is closely related to neovascularization of macroporous biomaterials implanted in vivo. A large pore size is beneficial for the growth of blood vessels, and the diameter of a pore smaller than 400 μm limits the growth of blood vessels and results in a smaller blood vessel diameter.


Xu L.,PLA Fourth Military Medical University
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery | Year: 2011

To evaluate the biomechanical characteristics of the decellularized laryngeal scaffold. Ten Chinese adult dogs were randomly divided into two groups: perfusion group (n = 5) and control group (n = 5). The acellular larynx scaffold was obtained from dogs through cranial thyroid arteries perfusion with detergents. Comparative examinations were performed by the macroscopic view, histological view (hematoxylin and eosin stain, Alcian blue stain and Masson stain), scanning electron microscope (SEM) and biomechanical properties between perfusion group and control group. Macroscopic view showed that the decellularized laryngeal scaffold appeared pale asphyxia. HE stain indicated that there were little acellular traces of muscle and mucosa. Alcian blue stain, Masson stain and scanning electron microscope (SEM) suggested that there were no obvious changes about glycosaminoglycan and collagen. The compressive modulus of thyroid cartilage was (1.06 ± 0.07) MPa (x(-) ± s) in experimental groups and (1.15 ± 0.11) MPa in control group, showing no significant difference (t = 1.424, P > 0.05), neither in compressive modulus of annular cartilage (1.68 ± 0.11) MPa in experimental groups and (1.67 ± 0.09) MPa in control group (t = 0.185, P > 0.05). The tensile strength of thyroid cartilage between experimental (5.74 ± 0.88) MPa and control groups (6.18 ± 1.33) MPa did not have the statistical significance (t = 0.627, P > 0.05). These results indicate that perfusion method can construct a perfect biomechanical acellular larynx scaffold which could be a better selection for laryngeal reconstruction with tissue engineering method.


Xu W.D.,PLA Fourth Military Medical University
Zhonghua er ke za zhi. Chinese journal of pediatrics | Year: 2011

To look for the evidences of motilin receptor expression on interstitial cells of Cajal (ICC) of the rabbit. Smooth muscle segments with ICC were isolated from the small intestine of 10-day old rabbits. The tissue segments equilibrated in Ca(2+)-free Hanks' solution were dispersed with an enzyme solution containing collagenase type II and then Ficoll density centrifugation was used to dissociate ICC. The cells were suspended and cultured in the M199 medium. The c-kit antibody was applied to distinguish the cultured ICC. The motilin receptor was identified by immunocytochemical assay with GPR38 antibody, c-kit antibody and hoechst 33342 combined to label ICC. Cells cultured for a few days were sorted for ICC with c-kit stained green fluorescent through flow cytometry. The total RNA and proteins extracted from the sorted ICC were respectively used to verify motilin receptor on the ICC by reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blotting. We had successfully dissociated and cultured ICC of rabbit small intestine in vitro. Fluorescent staining with c-kit antibody confirmed that the culture ICC was successful. Triple-labeled immunofluorescent staining had detected the motilin receptor on membrane of ICC. Flow cytometry analysis showed that the ratio of c-kit positive cell in the cultured cells was 64.3%. The number of sorted ICC was 6.7 × 10(5) and 5.6 × 10(6). The results of RT-PCR and Western blot confirmed that the ICC had motilin receptor expression. Our study demonstrated presence of motilin receptor on ICC of the rabbit. The present results may suggest that ICC play an important role in gastrointestinal movement induced by motilin.


Liu S.,CAS Institute of Biophysics | Zhang H.,CAS Institute of Biophysics | Li M.,CAS Institute of Biophysics | Hu D.,CAS Institute of Biophysics | And 4 more authors.
Cell Death and Differentiation | Year: 2013

Activating and inhibitory receptors control natural killer (NK) cell activity. T-cell immunoglobulin and ITIM (immunoreceptor tyrosine-based inhibition motif) domain (TIGIT) was recently identified as a new inhibitory receptor on T and NK cells that suppressed their effector functions. TIGIT harbors the immunoreceptor tail tyrosine (ITT)-like and ITIM motifs in its cytoplasmic tail. However, how its ITT-like motif functions in TIGIT-mediated negative signaling is still unclear. Here, we show that TIGIT/PVR (poliovirus receptor) engagement disrupts granule polarization leading to loss of killing activity of NK cells. The ITT-like motif of TIGIT has a major role in its negative signaling. After TIGIT/PVR ligation, the ITT-like motif is phosphorylated at Tyr225 and binds to cytosolic adapter Grb2, which can recruit SHIP1 to prematurely terminate phosphatidylinositol 3-kinase (PI3K) and MAPK signaling, leading to downregulation of NK cell function. In support of this, Tyr225 or Asn227 mutation leads to restoration of TIGIT/PVR-mediated cytotoxicity, and SHIP1 silencing can dramatically abolish TIGIT/PVR-mediated killing inhibition. © 2013 Macmillan Publishers Limited All rights reserved.


Wang S.-J.,Chinese Academy of Sciences | Yang H.-Y.,Capital Medical University | Xu G.-S.,PLA Fourth Military Medical University
Evidence-based Complementary and Alternative Medicine | Year: 2012

Here we used a mouse model of zymosan-induced colorectal hypersensitivity, a similar model of IBS in our previous work, to evaluate the effectiveness of the different number of times of acupuncture and elucidate its potential mechanism of EA treatment. Colorectal distension (CRD) tests show that intracolonic zymosan injection does, while saline injection does not, induce a typical colorectal hypersensitivity. EA treatment at classical acupoints Zusanli (ST36) and Shangjuxu (ST37) in both hind limbs for 15 min slightly attenuated and significantly blunted the hypersensitive responses after first and fifth acupunctures, respectively, to colorectal distention in zymosan treatment mice, but not in saline treatment mice. Western blot results indicated that ion channel and TrpV1 expression in colorectum as well as ERK1/2 MAPK pathway activation in peripheral and central nerve system might be involved in this process. Hence, we conclude that EA is a potential therapeutic tool in the treatment and alleviation of chronic abdominal pain, and the effectiveness of acupuncture analgesia is accumulative with increased number of times of acupuncture when compared to that of a single time of acupuncture. © 2012 Shao-Jun Wang et al.


Sun J.,U.S. National Institutes of Health | Aponte A.M.,U.S. National Institutes of Health | Kohr M.J.,U.S. National Institutes of Health | Kohr M.J.,Johns Hopkins Medical Institutions | And 4 more authors.
Free Radical Biology and Medicine | Year: 2013

Nitric oxide (NO) plays an important role in acute ischemic preconditioning (IPC). In addition to activating soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signaling pathways, NO-mediated protein S-nitros(yl)ation (SNO) has been recently shown to play an essential role in cardioprotection against ischemia-reperfusion (I/R) injury. In our previous studies, we have shown that IPC-induced cardioprotection could be blocked by treatment with either N-nitro-L-arginine methyl ester (L-NAME, a constitutive NO synthase inhibitor) or ascorbate (a reducing agent to decompose SNO). To clarify NO-mediated sGC/cGMP/PKG-dependent or -independent (i.e., SNO) signaling involved in IPC-induced cardioprotection, mouse hearts were Langendorff-perfused in the dark to prevent SNO decomposition by light exposure. Treatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, a highly selective inhibitor of sGC) or KT5823 (a potent and selective inhibitor of PKG) did not abolish IPC-induced acute protection, suggesting that the sGC/cGMP/PKG signaling pathway does not play an important role in NO-mediated cardioprotective signaling during acute IPC. In addition, treatment with ODQ in IPC hearts provided an additional protective effect on functional recovery, in parallel with a higher SNO level in these ODQ+IPC hearts. In conclusion, these results suggest that the protective effect of NO is not related primarily to activation of the sGC/cGMP/PKG signaling pathway, but rather through SNO signaling in IPC-induced acute cardioprotection.


Dong W.,260th Hospital of the PLA | Zhu P.,PLA Fourth Military Medical University
Autoimmunity Reviews | Year: 2012

Th17 cells selectively produce the signature cytokines such as IL-17, IL-21 and IL-22, and play a critical role for the chronic inflammatory response and subsequent tissue damage in synovial joints of patients with rheumatoid arthritis (RA). The preliminary clinical study indicates that IL-17 neutralizing therapy can ameliorate inflammatory cascades within peripheral synovial joints in the major population of patients with active RA. Multiple cellular and molecular modulations for the Th17-cell-polarized responses could exist, however, in the inflamed synovium, possibly resulting in a functional niche for the generation and activation of pathogenic Th17 cells. This might establish a vicious cycle culminating in the striking marginal erosions of cartilage and bone in the RA joints, and at least partially abrogate the potential therapeutic benefits related to IL-17 antagonizing or Th17-cell depleting therapy. This article is aimed to discuss the cellular and molecular pathways critically involved in the expansion and activation of pathogenic Th17 cells in RA synovium, with emphasis on the potential therapeutic implications for targeting these pathways to the present and future RA clinics. © 2012 Elsevier B.V.


Wang Y.,PLA Fourth Military Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2011

To construct and express a trichosanthin(TCS)gene mutant and purify the expressed product. Predict the potential antigenic determinant on TCS molecule by computer modeling and induce site-directed mutation. Amplify gene mutant TCS(RL28-29CG); by PCR using the genomic DNA of Trichosanthes kirilowii as a template and insert into expression vector pRSET-A, then transform to E.coli BL21(DE3)for expression under induction of IPTG. Purify the expressed product by Ni-NTA afinity column chromatography. The target protein in a soluble form was successfully expressed in E.coli. Homogenous TCS mutant protein was obtained after purification of expressed product. TCS mutant gene TCS(RL28-29CG); is succ-essfully constructed and expressed.


Zhuang Y.,PLA Fourth Military Medical University
AIDS research and human retroviruses | Year: 2012

Regulatory T cell (Treg) is a subset of CD4(+) T cells that play a critical role in regulating the immune responses. Human immunodeficiency virus (HIV) infection is associated with T cell abnormalities and alters effector T cell function. There are a large number of patients coinfected with HIV and hepatitis C virus (HCV). Here, we evaluated the proportion of CD4(+) Treg cells expressing CD25 and FOXP3, and the status of immune activation of CD8(+) T cells in 60 Chinese patients chronically infected with HIV and/or HCV. Furthermore, we investigated the influence of highly active antiretroviral therapy (HAART) on the level of Treg cells and immune activated CD8(+) T cells. We observed that the Treg level was upregulated in HIV infection and HCV infection could not enhance this kind of upregulation significantly. The level of Treg cells was negatively correlated with CD4(+) T cell counts and positively correlated with HIV viral loads. We observed considerably elevated CD38 and HLA-DR expression in CD8(+) T cells in HIV-infected subjects but not in HCV-infected patients in comparison to that in healthy controls. There is no significant difference concerning the proportion of CD8(+) T cells expressing CD38 or HLA-DR between HIV-1-monoinfected and HIV/HCV-coinfected patients. After 12-week HAART, the proportion of Treg cells dropped, but still more than the level in healthy controls. HAART could reverse the abnormal immune activation of CD8(+) T cells. The decrease of Tregs did not alter the downregulation of HIV-1-specific CTL responses in these HIV-infected patients after HAART therapy. The level of HIV virus might be the key point for the decline of CTL responses.


Munir K.M.,University of Maryland Baltimore County | Chandrasekaran S.,University of Maryland Baltimore County | Gao F.,PLA Fourth Military Medical University | Quon M.J.,University of Maryland Baltimore County
American Journal of Physiology - Endocrinology and Metabolism | Year: 2013

The rising epidemic of diabetes is a pressing issue in clinical medicine worldwide from both healthcare and economic perspectives. This is fueled by overwhelming increases in the incidence and prevalence of obesity. Obesity and diabetes are characterized by both insulin resistance and endothelial dysfunction that lead to substantial increases in cardiovascular morbidity and mortality. Reciprocal relationships between insulin resistance and endothelial dysfunction tightly link metabolic diseases including obesity and diabetes with their cardiovascular complications. Therefore, therapeutic approaches that target either insulin resistance or endothelial dysfunction alone are likely to simultaneously improve both metabolic and cardiovascular pathophysiology and disease outcomes. Moreover, combination therapies with agents targeting distinct mechanisms are likely to have additive or synergistic benefits. Conventional therapies for diabetes and its cardiovascular complications that are both safe and effective are insufficient to meet rising demand. Large, robust, epidemiologic studies demonstrate beneficial metabolic and cardiovascular health effects for many functional foods containing various polyphenols. However, precise molecular mechanisms of action for food polyphenols are largely unknown. Moreover, translation of these insights into effective clinical therapies has not been fully realized. Nevertheless, some functional foods are likely sources for safe and effective therapies and preventative strategies for metabolic diseases and their cardiovascular complications. In this review, we emphasize recent progress in elucidating molecular, cellular, and physiological actions of polyphenols from green tea (EGCG), cocoa (ECG), and citrus fruits (hesperedin) that are related to improving metabolic and cardiovascular pathophysiology. We also discuss a rigorous comprehensive approach to studying functional foods that is essential for developing novel, effective, and safe medications derived from functional foods that will complement existing conventional drugs. © 2013 the American Physiological Society.


Liu Y.,PLA Fourth Military Medical University
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery | Year: 2011

To investigate the presence of mesenchymal stem cells (MSC) in laryngeal mucosa, and to seek for the method to isolate, cultivate and identify these cells. Normal laryngeal mucosa was obtained from patients with laryngeal carcinoma during surgery, and the generating mesenchymal cells was obtained by digestive method. The cell growth curve was evaluated by 3-(4.5-methylthiazol-2yl)-2.5-diphenyltetrazolium bromide (MTT) assay. Colony forming cell assay was used to screen different morphologic colonies and evaluate clone formation ability. Flow cytometry was performed for the expression of the cells of the 4th passage surface marker profiles. Multiple differentiation potentials were confirmed by adipogenic, osteogenic and neural lineages induction. MTT assay and colony forming cell assay showed that laryngeal mucosa MSC had a relatively rapid proliferation capacity and a relatively high clone formation capacity (clone formation rate 7.1%). Flow cytometry analysis revealed that the laryngeal mucosa MSC were positive for CD29 (16.9%), CD44 (97.4%), CD90 (89.5%), CD105 (85.9%), CD146 (2.5%) and stro-1 (20.4%), but negative for CD34 (1.2%) and CD45 (0.8%). Laryngeal mucosa MSC undergone adipogenic, osteogenic and neural lineages induction were positive for oil red staining, alizarin red staining and S100 staining respectively, which suggested that laryngeal mucosa MSC could differentiate into adipogenic, osteogenic and neural lineages. This study demonstrated that MSC with rapid proliferative capacity and multiple differentiation potential could be obtained from lamina propria of laryngeal mucosa.


Liu H.,PLA Fourth Military Medical University
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2013

To review and summarize the surgical techniques and their outcomes for the treatment of lumbar spondylolysis in young patients by direct surgical repair. Both home and abroad literature on the surgical techniques and their outcomes respectively for the treatment of lumbar spondylolysis in young patients by direct surgical repair was reviewed extensively and summarized. Direct surgical repair of lumbar spondylolysis can offer a simple reduction and fixation for the injured vertebra, which is also in accord with normal anatomy and physiology. In this way, normal anatomy of vertebra can be sustained. As reported surgical techniques of direct repair, such as single lag screw, hook screw, cerclage wire, pedicle screw cable, pedicle screw rod, and pedicle screw hook system, they all can provide acceptable results for lumbar spondylolysis in young patients. Furthermore, to comply strictly with the inclusion criteria of surgical management and select the appropriate internal fixation can also contribute to a good effectiveness. Within the various methods of internal fixation, pedicle screw hook system has been widely recognized. Pedicle screw hook system fixation is simple and safe clinically. With the gradual improvement of this method and the development of minimally invasive technologies, it will have broad application prospects.


Chen R.,Shaanxi Normal University | Wang J.-B.,Shaanxi Normal University | Zhang X.-Q.,PLA Fourth Military Medical University | Ren J.,Shaanxi Normal University | Zeng C.-M.,Shaanxi Normal University
Archives of Biochemistry and Biophysics | Year: 2011

Increasing evidence has demonstrated that EGCG possesses prooxidant potential in biological systems, including modifying proteins, breaking DNA strands and inducing the generation of reactive oxygen species. In the present study, the prooxidant effect of EGCG on erythrocyte membranes was investigated. SDS-PAGE and NBT-staining assay were utilized to detect the catechol-protein adducts that generated upon treating the membranes with EGCG. The results indicated that EGCG was able to bind covalently to sulfhydryl groups of membrane proteins, leading to the formation of protein aggregates with intermolecular cross-linking. We suggested that the catechol-quinone originated from the oxidation of EGCG acted as a cross-linker on which peptide chains were combined through thiol-S-alkylation at the C2- and C6-sites of the gallyl ring. EGC showed similar effects as EGCG on the ghost membranes, whereas ECG and EC did not, suggesting that a structure with a gallyl moiety is a prerequisite for a catechin to induce the aggregation of membrane proteins and to deplete membrane sulfhydryls. EDTA and ascorbic acid inhibited the EGCG-induced aggregation of membrane proteins by blocking the formation of catechol-quinone. The information of the present study may provide a fresh insight into the prooxidant effect and cytotoxicity of tea catechins. © 2011 Elsevier Inc. All rights reserved.


Tan H.,University of South Carolina | Biechler S.,University of South Carolina | Junor L.,University of South Carolina | Yost M.J.,University of South Carolina | And 4 more authors.
Developmental Biology | Year: 2013

Fibrous development of the extracellular matrix (ECM) of cardiac valves is necessary for proper heart function. Pathological remodeling of valve ECM is observed in both pediatric and adult cardiac disorders. It is well established that intracardiac hemodynamics play a significant role in the morphogenesis of cardiovascular tissues. However, the mechanisms that transduce mechanical forces into morphogenetic processes are not well understood. Here, we report the development of a three-dimensional, in vitro culture system that allows for culture of embryonic valve tissue under specific pulsatile flow conditions. This system was used to investigate the role that fluid flow plays in fibrous ECM expression during valve formation and to test the underlying cellular mechanisms that regulate this mechanotransduction. When cultured under pulsatile flow, developing valve tissues upregulated fibrous ECM expression at both the transcript and protein levels in comparison to no-flow controls. Flow-cultured valve tissues also underwent morphological development, as cushions elongated into leaflet-like structures that were absent in no-flow controls. Furthermore, rhoA, a member of the cytoskeletal actin-regulating GTPase family of proteins, was upregulated and activated by flow culture. Inhibition of the downstream rhoA effector kinase, ROCK, blocked flow-driven fibrous ECM accumulation and tissue stiffening, while the addition of lysophosphatidic acid (LPA), a rhoA activator, stimulated fibrous ECM deposition and tissue stiffening. These results support a prominent role for the rhoA pathway in the mechanotransduction of hemodynamic forces during fibrous remodeling of developing valve tissue. Our results also point to a potential link between regulation of the actinomyosin cytoskeleton and fibrous ECM synthesis in cardiovascular tissues. © 2012 Elsevier Inc.


Hu S.-J.,PLA Fourth Military Medical University
Cancer Research and Clinic | Year: 2013

Objective: To construct and identify the recombinant adenovirus carrying with MAGE-D4a gene. Methods: The MAGE-D4a sequencing was performed by reverse transcription RNA (RT-PCR) from Glioma cell line U251, and inserted the adenoviral shuttle vector-pTracer-GFP. Then it was linearized with PmeI and cotransformed with El-deleted adenoviral backbone AdEasy-1 into the competent bacterial strain BJ5183, which allows efficient recombination to occur. After screening, recombinants for adenoviruses Ad/MAGE-D4a and Ad-GFP, which contains no insert sequence as a control, were generated. The recombinant DNA was identified by restriction endonuclease PacI and transfected into HEK 293 cells after linearization. The cells were harvested when a cytopathic effect appeared, and the generated recombinant adenoviruses were isolated. Results: According to the result of RT-PCR, the MAGE-D4a gene was expressed by the recombinant adenovirus and the titers were 2×108 pfu/ml. Conclusions: The recombinant adenovirus Ad/MAGE-D4a was successfully constructed, and the establishment of stably transfected HEK293 cell lines provided an original method for oncotherapy with MAGE-D4a gene.


Qian N.-S.,Chinese PLA General Hospital | Liao Y.-H.,PLA Fourth Military Medical University | Cai S.-W.,Chinese PLA General Hospital | Raut V.,Kyoto University | Dong J.-H.,Chinese PLA General Hospital
Hepatobiliary and Pancreatic Diseases International | Year: 2013

BACKGROUND: Liver surgery has gone through the phases of wedge liver resection, regular resection of hepatic lobes, irregular and local resection, extracorporeal hepatectomy, hemi-extracorporeal hepatectomy and Da Vinci surgical system-assisted hepatectomy. Taking advantage of modern technologies, liver surgery is stepping into an age of precise liver resection. This review aimed to analyze the comprehensive application of modern technologies in precise liver resection. DATA SOURCE: PubMed search was carried out for English-language articles relevant to precise liver resection, liver anatomy, hepatic blood inflow blockage, parenchyma transection, and down-staging treatment. RESULTS: The 3D image system can imitate the liver operation procedures, conduct risk assessment, help to identify the operation feasibility and confirm the operation scheme. In addition, some techniques including puncture and injection of methylene blue into the target Glisson sheath help to precisely determine the resection. Alternative methods such as Pringle maneuver are helpful for hepatic blood inflow blockage in precise liver resection. Moreover, the use of exquisite equipment for liver parenchyma transection, such as cavitron ultrasonic surgical aspirator, ultrasonic scalpel, Ligasure and Tissue Link is also helpful to reduce hemorrhage in liver resection, or even operate exsanguinous liver resection without blocking hepatic blood flow. Furthermore, various down-staging therapies including transcatheter arterial chemoembolization and radio-frequency ablation were appropriate for unrespectable cancer, which reverse the advanced tumor back to early phase by local or systemic treatment so that hepatectomy or liver transplantation is possible. CONCLUSIONS: Modern technologies mentioned in this paper are the key tool for achieving precise liver resection and can effectively lead to maximum preservation of anatomical structural integrity and functions of the remnant liver. In addition, large randomized trials are needed to evaluate the usefulness of these technologies in patients with hepatocellular carcinoma who have undergone precise liver resection. © 2013, Hepatobiliary Pancreat Dis Int. All rights reserved.


A novel single isomer of positively charged β-cyclodextrin, mono-6-deoxy-6-((2S,3S)-(+)-2,3-O-isopropylidene-1,4-tetramethylenediamine)-β-CD (MIPTACD) was designed and synthesized in seven steps starting from commercially available (2R,3R)-tartaric acid. The chiral resolution abilities of the new cationic chiral selector were studied by capillary electrophoresis using 10 different dansyl (Dns)-amino acids and N-acetylphenylalanine (N-Ac-Phe) as model analytes. The effects of running buffer pH and chiral selector concentration on the separation selectivity, resolutions, and migration times of analytes were studied in detail. MIPTACD shows a very good chiral recognition ability even at very low concentrations at the investigated pH values, as shown by the very large values of selectivity and resolution towards amino acids enantiomers to be assessed. © 2010 Wiley-Liss, Inc.


Zhang H.-M.,PLA Fourth Military Medical University | Zhang Y.,University of Texas Health Science Center at San Antonio
Journal of Pineal Research | Year: 2014

Melatonin (N-acetyl-5-methoxytryptamine), an indoleamine produced in many organs including the pineal gland, was initially characterized as a hormone primarily involved in circadian regulation of physiological and neuroendocrine function. Subsequent studies found that melatonin and its metabolic derivatives possess strong free radical scavenging properties. These metabolites are potent antioxidants against both ROS (reactive oxygen species) and RNS (reactive nitrogen species). The mechanisms by which melatonin and its metabolites protect against free radicals and oxidative stress include direct scavenging of radicals and radical products, induction of the expression of antioxidant enzymes, reduction of the activation of pro-oxidant enzymes, and maintenance of mitochondrial homeostasis. In both in vitro and in vivo studies, melatonin has been shown to reduce oxidative damage to lipids, proteins and DNA under a very wide set of conditions where toxic derivatives of oxygen are known to be produced. Although the vast majority of studies proved the antioxidant capacity of melatonin and its derivatives, a few studies using cultured cells found that melatonin promoted the generation of ROS at pharmacological concentrations (μm to mm range) in several tumor and nontumor cells; thus, melatonin functioned as a conditional pro-oxidant. Mechanistically, melatonin may stimulate ROS production through its interaction with calmodulin. Also, melatonin may interact with mitochondrial complex III or mitochondrial transition pore to promote ROS production. Whether melatonin functions as a pro-oxidant under in vivo conditions is not well documented; thus, whether the reported in vitro pro-oxidant actions come into play in live organisms remains to be established. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Zhang Z.-M.,PLA Fourth Military Medical University
Chinese Journal of Ophthalmology | Year: 2013

Visual evoked potential testing items depend on stimuli and recording parameters. There is great variation in flash visual evoked potential (FVEP), while the pattern visual evoked potential (PVEP) is stable. The later is taken as the main objective assessment of visual function indicators in clinical. Only when PVEP cannot be recorded or the waves are hard to be recognized, the FVEP will be a reference indicator. There is less clinical meaning to do FVEP testing alone. Recommended visual evoked potential and electroretinogram in combination will be more comprehensive response visual function. If it is necessary, electrooculogram, multifocal electroretinogram, pattern electroretinogram should apply to test together in some case. Multifocal visual evoked potential (mfVEP) were developed to record local field response, such as the early field change in glaucoma. The mfVEP is not a small version of the conventional visual evoked potential, since the generated source in both is different. The waves of mfVEP are related to the stimulation (spatial, temporary and contrast), recording channel (single, double or four), and method for signal extracting and signal nose ration. It is a potential Objective: assessment method for retinal ganglion cell or optic nerve and still needs further improvement. There will be variable and fluctuation in any visual electrophysiological testing results, the explanation for the Results: should be relay on complains, symptom, signs and other laboratory examination results. Copyright © 2013 by the Chinese Medical Association.


Yuan T.-F.,Nanjing Normal University | Li J.,PLA Fourth Military Medical University | Ding F.,Nanjing Normal University
Cell and Tissue Research | Year: 2014

Adult neurogenesis in rodents has been extensively studied. Here, we briefly summarize the studies of adult neurogenesis based on non-human primate brains and human postmortem brain samples in recent decades. The differences between rodent, primate and human neurogenesis are discussed. We conclude that these differences may contribute to distinct physiological roles and the self-repair mechanisms in the brain across species. © 2014, Springer-Verlag Berlin Heidelberg.


Wang H.-Q.,PLA Fourth Military Medical University | Samartzis D.,University of Hong Kong
International Journal of Clinical and Experimental Pathology | Year: 2014

As a significant determinant of low back pain, intervertebral disc degeneration (IDD) has attracted more and more attention of both investigators and physicians. Disc herniation, termed as intervertebral disc displacement, is amongst the most prevalent spinal diseases closely linked with IDD. Due to the same origins and similar pathophysiology, the ambiguity regarding the similarity and difference of IDD and intervertebral disc displacement thus remains. The aim of this study was to clarify the nomenclature of IDD and disc herniation in terms of molecular etiology, pathophysiology, nature history and clinical outcomes. Collectively, IDD is a type of multifaceted, progressive spinal disease with or without clinical symptoms as back pain, characterized by extracellular matrix and the integrity of NP and AF lost, fissures formation. Disc herniation (termed as intervertebral disc displacement) is a type of spinal disease based on IDD or not, with local pain and/or sciatica due to mechanical compression and autoimmune cascades upon the corresponding nerve roots. Clarifying the nomenclature of intervertebral disc degeneration and displacement has important implications both for investigators and for physicians.


Zhang Y.,University of Michigan | Yan W.,University of Michigan | Collins M.A.,University of