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Yuzhong Chengguanzhen, China

Chongqing Medical University , previously referred to as the Chongqing University of Medical science , was established in 1956 in Chongqing, China. It was originally a branch of the Shanghai First Medical College . Wikipedia.

Duan F.-T.,Sun Yat Sen University | Qian F.,Chongqing Medical University | Fang K.,Sun Yat Sen University | Lin K.-Y.,Sun Yat Sen University | And 2 more authors.
Molecular Cancer | Year: 2013

Background: MicroRNA-133b (miR-133b), which is a muscle-specific microRNA, has been reported to be downregulated in human colorectal carcinoma (CRC) when compared to adjacent non-tumor tissue. However, its diagnostic value and role in CRC have yet to be described. CXC chemokine receptor-4 (CXCR4), which participates in multiple cell processes such as cell invasion-related signaling pathways, was predicted to be a potential target of miR-133b. The aim of this study was to investigate the associations and functions of miR-133b and CXCR4 in CRC initiation and invasion.Methods: Mature miR-133b and CXCR4 expression levels were detected in 31 tumor samples and their adjacent, non-tumor tissues from patients with CRC, as well as in 6 CRC cell lines, using real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays and Western blots were used to validate CXCR4 as a putative target gene of miR-133b. Regulation of CXCR4 expression by miR-133b was assessed using qRT-PCR and Western blot analysis, and the effects of exogenous miR-133b and CXCR4 on cell invasion and migration were evaluated in vitro using the SW-480 and SW-620 CRC cell lines.Results: A significant downregulation of miR-133b was observed in 93.55% of CRC tissues, and the expression of miR-133b was much lower in metastatic tumors (stage C and D, stratified by the Modified Dukes Staging System) than in primary tumors (stage A and B). In contrast, CXCR4 protein expression significantly increased in 52.63% of CRC samples, and increased CXCR4 expression in CRC was associated with advanced tumor stage. CXCR4 was shown to be a direct target of miR-133b by luciferase reporter assays, and transfection of miR-133b mimics inhibited invasion and stimulated apoptosis of SW-480 and SW-620 CRC cells.Conclusions: Our study demonstrated that downregulated miR-133b contributed to increased cell invasion and migration in CRC by negatively regulating CXCR4. These findings may be significant for the development of therapy target for CRC. © 2013 Duan et al.; licensee BioMed Central Ltd.

Sun Y.,University of California at Davis | Do H.,University of California at Davis | Gao J.,University of California at Davis | Gao J.,Yunnan Normal University | And 4 more authors.
Current Biology | Year: 2013

Sensing of an electric field (EF) by cells - galvanotaxis - is important in wound healing [1], development [2], cell division, nerve growth, and angiogenesis [3]. Different cell types migrate in opposite directions in EFs [4], and the same cell can switch the directionality depending on conditions [5]. A tug-of-war mechanism between multiple signaling pathways [6] can direct Dictyostelium cells to either cathode or anode. Mechanics of motility is simplest in fish keratocytes, so we turned to keratocytes to investigate their migration in EFs. Keratocytes sense electric fields and migrate to the cathode [7, 8]. Keratocyte fragments [9, 10] are the simplest motile units. Cell fragments from leukocytes are able to respond to chemotactic signals [11], but whether cell fragments are galvanotactic was unknown. We found that keratocyte fragments are the smallest motile electric field-sensing unit: they migrate to the anode, in the opposite direction of whole cells. Myosin II was essential for the direction sensing of fragments but not for parental cells, while PI3 kinase was essential for the direction sensing of whole cells but not for fragments. Thus, two signal transduction pathways, one depending on PI3K, another on myosin, compete to orient motile cells in the electric field. Galvanotaxis is not due to EF force and does not depend on cell or fragment size. We propose a "compass" model according to which protrusive and contractile actomyosin networks self-polarize to the front and rear of the motile cell, respectively, and the electric signal orients both networks toward cathode with different strengths. © 2013 Elsevier Ltd.

Wang L.,Chongqing Medical University
Medical science monitor basic research | Year: 2013

The integrin β1 subunit and its downstream molecules such as integrin-linked kinase (ILK) and focal adhesion kinase (FAK) are indispensable to the inhibition of postinfarction cardiac remodeling, ischemic cardiomyopathy, and heart failure. As a component of the integrin pathway, C3G (Crk SH3-domain-binding guanine nucleotide exchange factor) protein may also participate in postinfarction cardiac remodeling, ischemic cardiomyopathy, and heart failure. Experimental myocardial infarction (MI) and sham-operation (sham) models were set up in Sprague-Dawley rats. C3G protein expression in the myocardium in the sham group and in the non-infarcted myocardium of the peri-infarct zones in the MI group was examined by Western blot. The C3G protein expression in the myocardium was 0.22±0.06, n=8 in the post-sham 24-hour group; 0.29±0.10, n=8 in the post-MI 24-hour group; 0.22±0.07, n=8 in the post-sham 12-week group; and 0.56±0.14, n=8 in the post-MI 12-week group. The C3G protein expression in the myocardium in the post-MI 12-week group was significantly elevated compared to that in the post-sham 12-week group (p=0.0002), in the post-sham 24-hour group (p=0.0002), and in the post-MI 24-hour group (p=0.0006). C3G protein expression exhibits in the myocardium of rats. Furthermore, C3G protein expression is significantly elevated in the non-infarcted myocardium of the peri-infarct zones. The elevated C3G protein expression could participate in postinfarction cardiac remodeling, ischemic cardiomyopathy, and heart failure.

Zeng Y.-Q.,Kunming Medical University | Wang Y.-J.,Chongqing Medical University | Zhou X.-F.,Kunming Medical University | Zhou X.-F.,University of South Australia
Frontiers in Neurology | Year: 2014

Background: Alzheimer's disease (AD) is a multifactorial disorder characterized by the progressive deterioration of neuronal networks. The clearance of Aß from the brain and anti-inflammation are potential important strategies to prevent and treat disease. In a previous study, we demonstrated the grape seed extract (GSE) could reduce brain Aß burden and microglia activation, but which polyphenol plays a major role in these events is not known. Here, we tested pharmacological effects of (-)epicatechin, one principle polyphenol compound in GSE, on transgenic AD mice. Methods: APP/PS1 transgenic mice were fed with (-)epicatechin diet (40 mg/kg/day) and curcumin diet (47 mg/kg/day) at 3 months of age for 9 months, the function of liver, Aß levels in the brain and serum, AD-type neuropathology, plasma levels of inflammatory cytokines were measured. Results: Toward the end of the experiment, we found long-term feeding of (-)epicatechin diet was well tolerated without fatality, changes in food consumption, body weight, or liver function. (-)Epicatechin significantly reduced total Aß in brain and serum by 39 and 40%, respectively, compared with control diet. Microgliosis and astrocytosis in the brain of Alzheimer's mice were also reduced by 38 and 35%, respectively. The (-)epicatechin diet did not alter learning and memory behaviors in AD mice. Conclusion: This study has provided evidence on the beneficial role of (-)epicatechin in ameliorating amyloid-induced AD-like pathology in AD mice, but the impact of (-)epicatechin on tau pathology is not clear, also the mechanism needs further research. © 2014 Zeng, Wang and Zhou.

Guo F.,Chongqing Medical University | Lai Y.,New York University | Tian Q.,New York University | Lin E.A.,New York University | And 2 more authors.
Arthritis and Rheumatism | Year: 2010

Objective. To determine 1) whether a protein interaction network exists between granulin-epithelin precursor (GEP), ADAMTS-7/ADAMTS-12, and cartilage oligomeric matrix protein (COMP); 2) whether GEP interferes with the interactions between ADAMTS-7/ADAMTS-12 metalloproteinases and COMP substrate, including the cleavage of COMP; 3) whether GEP affects tumor necrosis factor α (TNFα)-mediated induction of ADAMTS-7/ADAMTS-12 expression and COMP degradation; and 4) whether GEP levels are altered during the progression of arthritis. Methods. Yeast two-hybrid, in vitro glutathione S-transferase pull-down, and coimmunoprecipitation assays were used to 1) examine the interactions between GEP, ADAMTS-7/ADAMTS-12, and COMP, and 2) map the binding sites required for the interactions between GEP and ADAMTS-7/ADAMTS-12. Immunofluorescence cell staining was performed to visualize the subcellular localization of GEP and ADAMTS-7/ADAMTS-12. An in vitro digestion assay was employed to determine whether GEP inhibits ADAMTS-7/ADAMTS-12-mediated digestion of COMP. The role of GEP in inhibiting TNFα-induced ADAMTS-7/ADAMTS-12 expression and COMP degradation in cartilage explants was also analyzed. Results. GEP bound directly to ADAMTS-7 and ADAMTS-12 in vitro and in chondrocytes, and the 4 C-terminal thrombospondin motifs of ADAMTS-7/ADAMTS-12 and each granulin unit of GEP mediated their interactions. Additionally, GEP colocalized with ADAMTS-7 and ADAMTS-12 on the cell surface of chondrocytes. More importantly, GEP inhibited COMP degradation by ADAMTS-7/ADAMTS-12 in a dose-dependent manner through 1) competitive inhibition through direct protein-protein interactions with ADAMTS-7/ADAMTS-12 and COMP, and 2) inhibition of TNFα-induced ADAMTS-7/ADAMTS-12 expression. Furthermore, GEP levels were significantly elevated in patients with either osteoarthritis or rheumatoid arthritis. Conclusion. Our observations demonstrate a novel protein-protein interaction network between GEP, ADAMTS-7/ADAMTS-12, and COMP. Furthermore, GEP is a novel specific inhibitor of ADAMTS-7/ADAMTS-12-mediated COMP degradation and may play a significant role in preventing the destruction of joint cartilage in arthritis. © 2010, American College of Rheumatology.

Ma J.,Chongqing Medical University
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2013

To investigate the effects of naringenin on the learning and memory ability of Alzheimer disease (AD) rats. 30 male SD rats were randomly divided into control group (sham operation group), model group and naringenin group. AD model was established by injecting strepoztocin (3 mg/kg) twice into each of two intracerebroventriculas. Naringenin group were given intragastric administration of naringenin once a day for 3 weeks and the other two groups were given intragadtric administration of normal saline with the same dosage and time period. After 3 weeks, learning and memory ability in all the three groups were analyzed by Morris water maze, the activity of superoxide dismutase(SOD) and the content of malondialdehyde (MDA) of the rats' brain tissue was detected by chemical colorimetric determination. Observed the expressions of Abeta42 and Abeta40 by immunohistochemical method. The expression and degree of phosphorylation of tau protein was assayed by western blotting. 1. Compared with the sham operation group, the mean escape latency of the model group was significantly prolonged (P < 0.05) and the time that rats were in the platform quadrant was significantly shortened (P < 0.0.5). On the contrary, compared with the model group, the mean escape latency of naringenin group was significantly shortened (P < 0.05) and the time that rats were in the platform quadrant was significantly extended (P < 0.005). 2. The level of MDA in the model group, compared with the sham operation group group, was significantly increased (P < 0.05). Whereas, that of naringenin group, compared with the model group, was significantly decreased compared with the sham operation group (P < 0.05). The activity of SOD in the naringenin group was significantly increased comparing with the model group (P < 0.05). 3. The expressions of Abeta40 and Abeta42 in model group were obviously up-regulated. Instead, the expressions of Abeta40 and Abeta42 in the naringenin group were significantly down regulated. 4. There was no significant difference in the expression of tau protein among each groups. Nevertheless, the phosphorylation of tau protein in the model group was significantly enhanced than that in the control group (P < 0.05), and the phosphorylation of tau protein in the naringenin group was significantly reduced than that in the model group (P < 0.05). Naringenin can improve learning and memory ability of model rats with Alzheimer disease through the approach of oxidative stress.

Equine rotavirus (ERV) strain L338 (G13P[18]) has a unique G and P genotype. However, the evolutionary relationship of L338 with other ERVs is still unknown. Here whole genome analysis of the L338 ERV strain was independently performed. Its genotype constellations were determined as G13-P[18]-I6-R9-C9-M6-A6-N9-T12-E14-H11, confirming previous genotype assignments. The L338 strain only shared the P[18] and I6 genotypes with other ERVs. The nucleotide sequences of the other 9 RNA segments were different from those of cogent genes of all other group A rotavirus (RVA) strains including ERVs and formed unique phylogenetic lineages. The L338 evolutionary footprints were tentatively identified in both VP7 and VP4 amino acid sequences: two regions were found in VP7 and twelve in VP4. The conserved regions shared between L338 and other group A rotavirus strains (RVAs) indicated that L338 was more closely related genomically to animal and human RVAs other than ERVs, suggesting that L338 may not be an endogenous equine RV but have emerged as an interspecies reassortant with other RVA strains. Furthermore, genotype-specific motifs of all 27 G and 37 P types were identified in regions 7-1a (aa 91-100) of VP7 and regions 8-1 (aa146-151) and 8-3 (aa113-118 and 125-135) of VP4 (VP8*). © 2015 Elsevier B.V..

Huang Y.,Chongqing Medical University
The Tohoku journal of experimental medicine | Year: 2010

Interstitial cells of Cajal (ICC) are distributed throughout the gastrointestinal (GI) tract and have important functions in the control of GI motility. Loss of ICC is associated with several GI motility disorders; yet, the mechanisms modulating ICC survival and proliferation are not fully understood. Hydrogen sulfide (H(2)S) has been reported to be a gaseous transmitter that regulates cellular proliferation. This study aims to establish whether H(2)S participates in regulation of ICC proliferation. The effect of H(2)S was studied in primary cultures of ICC, prepared from the mouse small intestine. To determine the extent of ICC proliferation, we used immunofluorescent staining to study alterations in the number of cells expressing c-Kit(+) and CD44(+), markers for mature ICC. Phosphorylation of Akt was measured by Western blot analysis. Treatment with low concentrations of NaHS (H(2)S donor, 1-30 microM) showed no apparent toxicity, as judged from cell numbers. Importantly, treatment with NaHS (15 microM) for 24 hours increased the numbers of c-Kit(+)/CD44(+) ICC by 23.3 +/- 1.4% (P < 0.05). Moreover, NaHS increased Akt phosphorylation, which was prevented with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (5 microM). LY294002 also blocked the NaHS-mediated increase in the number of ICC. In addition, H(2)S enhanced the proliferation of mature ICC in the in vitro culture system used here in a concentration-dependent manner. The present study suggests that H(2)S may be a critical factor in maintaining ICC numbers and may have a novel, Akt-dependent role in proliferation of mature ICC.

Feng C.,Chongqing Medical University
Cellular Physiology and Biochemistry | Year: 2015

Intervertebral disc degeneration (IDD) is a widely recognized contributor to low back pain (LBP). The Prevention or reversal of IDD is a potential treatment for LBP. Unfortunately, current treatments for IDD are aimed at relieving symptoms rather than regenerating disc structure or function. Recently, the injection of growth factors and mesenchymal stem cell (MSC) transplantation have been shown to be promising biological therapies for IDD. Growth factors stimulate the proliferation of and matrix synthesis by intervertebral disc (IVD) cells, leading to the regeneration of degenerative discs. Growth factors, hypoxia and co-culture with nucleus pulposus (NP) cells induce MSCs to differentiate toward an NP-like phenotype, which can increase the number of functional cells in the IVD or enhance the function of endogenous disc cells to facilitate IVD regeneration. Therefore, the emerging roles of growth factors in IVD regeneration have piqued the interest of researchers. Growth factors including transforming growth factor-β (TGF-β), fibroblast growth factor (FGF), insulin-like growth factor-1 (IGF-1) and growth and differentiation factor-5 (GDF-5), among others, have been demonstrated to enhance anabolism in IVD cells and to induce NP-like differentiation of MSCs. However, the injection of TGF, IGF and FGF into human IVDs may induce unwanted blood vessel ingrowth, which accelerates the process of IDD, the injection of GDF-5 may not have the same effect. This finding suggests that GDF-5 is a preferable growth factor for use in IDD treatment compared with TGF, IGF and FGF. The GDF-5 gene is one of the few growth factor genes that have been found to be associated with IDD thus far; moreover, the GDF-5 gene defects lead to collagen and proteoglycan abnormalities in discs in mice, suggesting that GDF-5 contributes to the structural and functional maintenance of the IVD. This review is focused on the functions of GDF-5 in the IVD and on the association between GDF-5 and a genetic predisposition to IDD. The effects of GDF-5 on IVD regeneration and on MSC differentiation are also discussed. GDF-5 plays a crucial role in the pathogenesis of IDD and is a promising therapeutic agent for IDD. Additionally, stem cell transplantation has been shown to be a promising biological therapy for IDD. © 2015 S. Karger AG, Basel Copyright © 2015, S. Karger AG. All rights reserved.

Zhao H.,Imperial College London | Perez J.S.,Imperial College London | Lu K.,Chongqing Medical University | George A.J.T.,Imperial College London | Ma D.,Imperial College London
American Journal of Physiology - Renal Physiology | Year: 2014

Toll-like receptor-4 (TLR-4) has been increasingly recognized as playing a critical role in the pathogenesis of ischemia-reperfusion injury (IRI) of renal grafts. This review provides a detailed overview of the new understanding of the involvement of TLR-4 in ischemia-reperfusion injury of renal grafts and its clinical significance in renal transplantation. TLR-4 not only responds to exogenous microbial motifs but can also recognize molecules which are released by stressed and necrotic cells, as well as degraded products of endogenous macromolecules. Upregulation of TLR-4 is found in tubular epithelial cells, vascular endothelial cells, and infiltrating leukocytes during renal ischemia-reperfusion injury, which is induced by massive release of endogenous damage-associated molecular pattern molecules such as high-mobility group box chromosomal protein 1. Activation of TLR-4 promotes the release of proinflammatory mediators, facilitates leukocyte migration and infiltration, activates the innate and adaptive immune system, and potentiates renal fibrosis. TLR-4 inhibition serves as the target of pharmacological agents, which could attenuate ischemia-reperfusion injury and associated delayed graft function and allograft rejection. There is evidence in the literature showing that targeting TLR-4 could improve long-term transplantation outcomes. Given the pivotal role of TLR-4 in ischemia-reperfusion injury and associated delayed graft function and allograft rejection, inhibition of TLR-4 using pharmacological agents could be beneficial for long-term graft survival. © 2014 the American Physiological Society.

Li Y.,Chongqing Medical University
Nutrition | Year: 2014

Objective: Epidemiologic studies evaluating the association between the intake of vegetables and fruit and the risk for glioma have produced inconsistent results. Therefore, the aim of this study was to test the hypothesis that higher vegetable and fruit intake may have a protective effect on risk for glioma. Methods: Pertinent studies were identified by a search in PubMed, Web of Knowledge, and Wan Fang Med Online up to January 2014. Random-effect model was used to combine study-specific results. Publication bias was estimated using Begg's funnel plot and Egger's regression asymmetry test. Results: Fifteen studies involving 5562 cases focusing on vegetable intake and 17 studies involving 3994 cases of fruit intake compared with the risk for glioma were included in this meta-analysis. The combined relative risk (RR) of glioma associated with vegetable intake was 0.775 (95% confidence interval [CI], 0.688-0.872) overall, and the association for subgroup analysis by study design, sources of control, ethnicity, and number of cases was consistent with overall data. For fruit intake and glioma risk, significant protective associations were found in an Asian population (RR, 0.573; 95% CI, 0.346-0.947), but not in a white population. No publication bias was found. Conclusions: This analysis indicated that intake of vegetables might have a protective effect on glioma. The intake of fruit might have a protective effect on glioma in the Asian population; however, the results need to be confirmed. © 2014 Elsevier Inc.

Jiang T.,University of Arizona | Jiang T.,Fudan University | Tian F.,Shanghai JiaoTong University | Zheng H.,Chongqing Medical University | And 5 more authors.
Kidney International | Year: 2014

The generation of reactive oxygen species has a pivotal role in both acute and chronic glomerular injuries in patients with lupus nephritis. As the transcription factor Nrf2 is a major regulator of the antioxidant response and is a primary cellular defense mechanism, we sought to determine a role of Nrf2 in the progression of lupus nephritis. Pathological analyses of renal biopsies from patients with different types of lupus nephritis showed oxidative damage in the glomeruli, accompanied by an active Nrf2 antioxidant response. A murine lupus nephritis model using Nrf2 +/+ and Nrf2 -/- mice was established using pristine injection. In this model, Nrf2 -/- mice suffered from greater renal damage and had more severe pathological alterations in the kidney. In addition, Nrf2 +/+ mice showed ameliorative renal function when treated with sulforaphane, an Nrf2 inducer. Nrf2 -/- mice had higher expression of transforming growth factor β1 (TGFβ1), fibronectin, and iNOS. In primary mouse mesangial cells, the nephritogenic monoclonal antibody R4A activated the nuclear factor-kappa B (NF-κB) pathway and increased the level of reactive oxygen species, iNOS, TGFβ1, and fibronectin. Knockdown of Nrf2 expression aggravated all aforementioned responses induced by R4A. Thus, these results suggest that Nrf2 improves lupus nephritis by neutralizing reactive oxygen species and by negatively regulating the NF-κB and TGFβ1 signaling pathways. © 2013 International Society of Nephrology.

The stress neuropeptide, corticotropin-releasing hormone (CRH) is expressed in peripheral tissues and inflammatory sites and is implicated in the modulation of the inflammatory response in a paracrine/ autocrine manner. However, the mechanisms by which CRH expression is regulated in peripheral immune cells are unclear. In this article, we address this question by employing primary rat peritoneal macrophages treated with lipopolysaccharide (LPS). Our results showed that CRH could be detected at the mRNA and protein levels in normal peritoneal macrophages and the levels increased significantly and reached a peak at 4 h after stimulation with 100 ng/ml LPS. Furthermore, LPS-induced CRH expression was inhibited by pretreatment with PD98059, a specific MAP kinase inhibitor, in a dose-dependent fashion in which the mRNA and protein levels of CRH was decreased by 90% and 95%, respectively. In addition, pretreatment with 50 μM SB203580, a p38 MAPK inhibitor, led to the decrease of CRH mRNA level by about 41%. Altogether, these results demonstrate that LPS significantly upregulates CRH expression through MAP kinase signaling pathway in rat peritoneal macrophages.

Song S.,Chongqing Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2013

To investigate the role of nuclear factor-κB (NF-κB) activation in bilirubin-induced apoptosis of rat hippocampal neurons and the effect of TAT-NBD intervention on bilirubin neurotoxicity. Primary-cultured rat hippocampal neurons were treated with TAT-NBD in the initial 6 or 24 h or in the latter 6 h during a 24-h bilirubin exposure of the cells (early, continuous and late intervention groups, respectively). Immunocytochemistry was performed to detect NF-κB p65 protein expression, and the cell survival and apoptosis were assessed with a modified MTT assay, Annexin V-FITC/PI and TUNEL assay. IL-1β concentration in the supernatant was determined with ELISA. Compared with the control cells, bilirubin-treated cells showed a significantly increased NF-κB p65 protein expression (P<0.01), which reached the peak level at 6 and 24 h (P<0.01). The cell survival rate in early TAT-NBD intervention group was (80.784∓9.767)%, significantly lower than that of the control group (P<0.01) but higher than that of bilirubin group (P<0.01); the apoptotic rate in early TAT-NBD intervention group was significantly higher than that of control group (P<0.01) but lower than that of bilirubin group (P<0.01). IL-1β concentration was significantly lower in early TAT-NBD intervention group (15.348∓0.812 pg/ml) than in bilirubin group (P<0.05). The continuous and late TAT-NBD intervention groups showed comparable cell survival rate, apoptotic rate and IL-1β concentration with bilirubin group (P>0.05). NF-κB bidirectionally regulates bilirubin-induced apoptosis of rat hippocampal neurons. Selective inhibition of the early peak of NF-κB by TAT-NBD offers neuroprotective effect. TAT-NBD can be potentially used for prophylaxis of bilirubin-induced brain injury.

Wang P.,Chongqing Medical University
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban | Year: 2011

To explore the effects of toosendanin in inducing apoptosis of human hepatocarcinoma cell line SMMC-7721 and Hep3B, and its influence on the related genes, Bcl-2, Bax and Fas. The inhibitory rate of cell proliferation and cell growth curve were detected by MTT assay; morphological changes of cells were observed by inverted microscope; early stage apoptosis rate were detected by Annexin V-FITC/PI assay; relative activities of Caspase-3,-8 and-9 were analyzed by spectrophotometry; and the expressions of Bcl-2, Bax and Fas were detected using immunohistochemistry assay. Toosendanin presented significant inhibitory effect on proliferation of hepatocarcinoma cells in a time- and dose-dependent manner. After toosendanin treatment, the amount of cells was significantly reduced, shrunk in size and rounded in shape, with decreased adhesion ability. The apoptosis rates of SMMC-7721 cells and Hep3B cells treated with 0.5 micromol/L toosendanin for 72 h were 21.55% and 18.35% respectively, which were reduced after z-VAD-fmk (inhibitor of Caspase) treatment. The activities of Caspase-3,-8 and -9 all markedly enhanced after treatment in SMMC-7721 cells, while in Hep3B cells, activities of Caspase-3 and -9 enhanced, but that of Caspase-8 unchanged. As compared with the control group, after toosendanin treatment, expression of Bcl-2 decreased, and that of Bax and Fas increased in SMMC-7721 cells; but in Hep3B cells the expression of Bcl-2 decreased, that of Bax increased, and expression of Fas unchanged. Toosendanin could inhibit the proliferation and induce the apoptosis of both P53 and P53 human hepatocarcinoma cells, which involved the participation of mitochondria-dependent pathway. So it may be a kind of natural anti-cancer drug, playing its effect through P53 independent pathway.

Mao H.Y.,Chongqing Medical University
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology | Year: 2011

To compare the efficacy of interferon and thymosin alpha-1 combination therapy with interferon monotherapy for HBeAg positive chronic hepatitis B. The relevant randomized controlled trials were searched throughout PubMed, EBSCO, Cochrane Library, CBMdisc, VIP, WanFang since Janurary 1990. Studies were included if patients were followed up for at least 6 months after cessation of treatment. Meta-analysis was carried out with RevMan5.0 software. Subgroup analyses were used at different time of observation. Seven randomized controlled trials were included(535 patients in total). According to the results of meta-analysis, the combination therapy was remarkably more effective than monotherapy both at the end of the treatment and the follow-up in terms of HBV-DNA negative rate (54.9% vs 36.3%, OR=2.39, 95% CI=1.64-3.49, P value is less than 0.01; 58.6% vs 30.7%, OR=3.68, 95% CI=2.51-5.41, P value is less than 0.01, respectively), ALT normalization rate (74.5% vs 60.9%, OR=1.94, 95% CI=1.26-3.00, P value is less than 0.01; 74.0% vs 55.6%, OR=2.36, 95% CI=1.54-3.62, P value is less than 0.01, respectively), HBeAg loss rate (56.9% vs 36.7%, OR=2.38, 95% CI=1.61-3.51, P value is less than 0.01; 62.2% vs 33.2%, OR=3.42, 95% CI=2.31-5.06, P value is less than 0.01, respectively) , and HBeAg seroconversion rate (40.1% vs 29.0%, OR=1.65, 95% CI=1.10-2.47, P value is less than 0.05; 47.0% vs 29.5%, OR=2.13, 95% CI=1.43-3.16, P value is less than 0.01, respectively); the HBsAg loss rate of the combination therapy group was significantly higher than that of the monotherapy group only at the end of the follow-up (9.8% vs 3.7%, OR=2.92, 95% CI=1.09-7.76, P value is less than 0.05). Interferon and thymosin alpha-1 combination therapy achieves superior effect with no increase in the adverse effects as compared to interferon monotherapy for HBeAg positive chronic hepatitis B.

Zhong Y.,Chongqing Medical University
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2012

To understand the children neglect situation of left-behind children (children who do not grow up with their parents) and non-left-behind children in China's western rural and its influencing factors. Scales and evaluation methods in the "Chinese rural child neglected evaluation model" were used in this study. The investigation was conducted by using multistage stratified cluster sampling method; three countries were sampled randomly in Shanxi and Chongqing in November 2010, respectively. And, in every county, children from rural area aged from zero to six were randomly selected, with neglect rate and degree to describe their neglected status, using logistic regression analysis to analyze factors affecting the neglect rate. Among 1568 subjects (859 left-behind and 709 living-with-parents), the total neglect rates were 29.78% (467/1568), and the total neglect degrees were 48.51 ± 6.49; the neglect rates for left-behind ones and living-with parents ones were 34.34% (295/859) and 24.26% (172/709) (P < 0.05); the neglect degree were 49.59 ± 6.54 and 47.19 ± 6.18 (P < 0.05). The neglect degree among left-behind ones and living-with parents ones between 0 to 2 years old were 48.59 ± 6.33 and 45.78 ± 5.94 (P < 0.05); in 3 to 6 years old group, which were 50.43 ± 6.60 and 48.25 ± 6.16(P < 0.05). The degrees in boy's group of these two kinds of children were 49.83 ± 6.67, 47.36 ± 6.28(P < 0.05) and girl's were 49.32 ± 6.38, 47.01 ± 6.08 (P < 0.05). On the other side, the neglect rate of left-behind and non-left-behind children between 0 to 2 years old were 39.33% (153/389) and 18.54% (56/302) (P < 0.05). The rates of boy's group were 34.91% (162/464) and 25.13% (94/374) (P < 0.05), and girl's were 33.67% (133/395) and 23.28% (78/335) (P < 0.05). Results showed that if the left-behind child's father was with lower education background, and the child and his mother feel stranger to each other, which led to the conclusion there was more chance for them to be neglected (OR values were 1.29 and 1.55, P < 0.05). If the non-neglected child's father was farmer or migrant worker and the relationship between the mother and father was poor, then there was more chance for them to be neglected (OR values were 0.85 and 1.92, P < 0.05). The situation of children neglect in the western rural regions in China is serious. Both the neglect rate and degree among left-behind children are higher than those living-with-parents children. The influencing factors of neglect rate are different in the two groups.

Yao L.,Chongqing Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2013

To investigate the protective effect of hydrogen against hyperoxia-induced oxidative stress injury in premature rat type II alveolar epithelial cells (AECs). The type II AECs isolated from premature rats were randomly divided into air (21% oxygen) control group, hyperoxia (95% oxygen) control group, air + hydrogen group, and hyperoxia+ hydrogen group. The cells with hydrogen treatment were cultured in the presence of rich hydrogen. After the corresponding exposure for 24 h, the cell morphology was observed microscopically. MTT assay was used to evaluated the cell proliferation ability, and JC-1 fluorescence probe was used to detect the mitochondrial membrane potential (δφ) changes of the type II AECs. The concentration of maleic dialdehyde (MDA) and superoxide dismutase (SOD) activity in the cell supernatant were detected using colorimetric method. No significant differences were found in cell growth or measurements between air control and air + hydrogen groups. Compared with air control group, the cells exposed to hyperoxia showed significantly suppressed proliferation, reduced mitochondrial membrane potential, increased MDA content, and decreased SOD activity. Intervention with hydrogen resulted in significantly increased cell proliferation and SOD activity and lowered MDA content, and restored the mitochondrial membrane potential in the cells with hyperoxia exposure (P<0.05). Hydrogen can significantly reduce hyperoxia-induced oxidative stress injury in premature rat type II AECs, improve the cellular antioxidant capacity, stabilize the mitochondrial membrane potential, and reduce the inhibitory effect of hyperoxia on cell proliferation.

Bai Y.-C.,Chongqing Medical University
Chinese Journal of Oncology | Year: 2011

Objective: To explore the expression of connective tissue growth factor (CTGF) in pancreatic cancer and its influence on the proliferation and migration of cancer cells. Methods: The expression of CTGF in pancreatic cell line PANC-1 cells was analyzed by real-time PCR and in pancreatic carcinoma (50 cases) tissues by immunohistochemistry. The ability of proliferation and migration in vitro of PANC-1 cells was tested by MTT assay, scratch test and Boyden chamber test after the CTGF gene was overexpressed by Ad5-CTGF or silenced with Ad5-siCTGF transfection. Results: CTGF was overexpressed in both pancreatic cancer cells and tissues. Overxpression of CTGF leads to increased proliferation and migration of PANC-1 cells. The CTGF-transfected PANC-1 cells showed apparent stronger proliferation ability and scratch-repair ability than that of empty vector controls. The results of Boyden chamber test showed that there were 34 cells/field (200 x magnificantion) of the CTGF-transfected overexpressing cells, much more than the 11 cells/field of the empty vector control cells; and 6 cells/microscopic field of the Ad5-siCTGF-transfected silenced cells, much less than the 15 cells/field of the control cells. Conclusions: CTGF is overexpressed in both pancreatic cancer cells in vitro and in vivo, indicating that it may play an important role in the cell proliferation and migration in pancreatic cancer.

Zhuo X.,Chongqing Medical University
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2012

Cytochrome P450 (CYP) 1A1 Ile462Val (exon7) polymorphism has been suggested to be a risk factor for several cancers. Published data on its association with oral cancer risk have generated conflicting results. Our previous meta-analysis containing data from prior to Jan 2008 regarding this issue failed to find a significant association between CYP1A1 Ile462Val variation and oral cancer susceptibility. An updated meta-analysis with eligible studies for the period up to May 2012 was conducted. Separate analyses on ethnicity and source of controls were also performed. A total of 13 case-control studies comprising 1,515 cases and 2,233 controls were lastly selected for analysis. Compared with the previous meta-analysis, the overall data also failed to indicate a significant association of CYP1A1 Ile462Val polymorphism with oral cancer risk (Val/Val vs. Ile/Ile--OR = 1.46; 95 % CI = 0.96-2.24; dominant model--OR = 1.01; 95 % CI = 0.81-1.25; and recessive model--OR = 1.46; 95 % CI = 0.96-2.23). However, in the subgroup analysis by ethnicity, increased cancer risk was observed among Asians under the additive and recessive models (Val/Val vs. Ile/Ile--OR = 1.74; 95 % CI = 1.04-2.90 and recessive model-OR = 1.73; 95 % CI = 1.04-2.87), inconsistent with the previous meta-analysis. Collectively, the data of the present study suggest that CYP1A1 variant Val/Val alleles might modify the susceptibility to oral cancer among Asians. Further well-designed investigations with large sample sizes are required to confirm this conclusion.

Zou S.,Chongqing 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 compare the difference of traumatic related index in serum and its significance between minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and open TLIF. Sixty patients were enrolled by the entry criteria between May and November 2012, and were divided into MIS-TLIF group (n = 30) and open TLIF group (n = 30). There was no significant difference in gender, age, type of lesions, disease segment, and disease duration between 2 groups (P > 0.05). The operation time, intraoperative blood loss, and postoperative hospitalization time were recorded, and the pain severity of incision was evaluated by visual analog scale (VAS). The serum levels of C-reactive protein (CRP) and creatine kinase (CK) were measured at preoperation and at 24 hours postoperatively. The levels of interleukin 6 (IL-6), IL-10, and tumor necrosis factor alpha (TNF-alpha) in serum were measured at preoperation and at 2, 4, 8, and 24 hours after operation. The operation time, intraoperative blood loss, and postoperative hospitalization time of MIS-TLIF group were significantly smaller than those of open TLIF group (P < 0.05), and the VAS score for incision pain in MIS-TLIF group was significantly lower than that of open TLIF group at 1, 2, and 3 days after operation (P < 0.05). The levels of CRP, CK, IL-6, and IL-10 in MIS-TLIF group were significantly lower than those in open TLIF group at 24 hours after operation (P < 0.05), but there was no significant difference between 2 groups before operation (P > 0.05). No significant difference was found in TNF-alpha level between 2 groups at pre- and post-operation (P > 0.05). Compared with the open-TLIF, MIS-TLIF may significantly reduce tissue injury and systemic inflammatory reactions during the early postoperative period.

Objective: To compare the predictive value of anatomic scoring system, physiological scoring system, and the combination of two systems in death prediction of patients with severe trauma in intensive care unit (ICU). Methods: A retrospective analysis of patients with severe trauma admitted to department of critical care medicine of Daping Hospital, the Third Military Medical University, and Zunyi Medical University from January 2011 to December 2014 was conducted. The patients meeting the following criteria were enrolled: over 16 years old, admitted to hospital shorter than 24 hours after trauma, length of ICU stay ≥ 48 hours, and injury severity score (ISS) ≥ 16. Patients were divided into two groups: survivors and non-survivors. The data of anatomic scoring system, including ISS and new injury severity score (NISS), and physiological scoring system, including acute physiology and chronic health evaluation II (APACHE II) score were collected. The predictive power for death of the scoring system alone or combination in patients with severe trauma was evaluated. Results: A total of 614 patients with severe trauma were enrolled, and there were 153 deaths with a mortality rate of 24.9%. ISS, NISS, APACHE II, ISS + APACHE II, NISS + APACHE II of non-survivors were significantly higher than those of survivors (ISS: 29.15 ± 7.75 vs. 24.31 ± 6.50, NISS: 41.96 ± 12.01 vs. 29.64 ± 8.19, APACHE II : 23.71 ± 6.58 vs. 17.02 ± 5.49, ISS + APACHE II : 52.86 ± 10.00 vs. 41.33 ± 8.70, NISS + APACHE II : 65.67 ± 13.46 vs. 46.66 ± 10.43, all P < 0.01). The area under receiver operating characteristic curve (AUC) of ISS, NISS, APACHE II, ISS + APACHE II, NISS + APACHE II was 0.687, 0.792, 0.782, 0.809, and 0.860, respectively. Both of ISS + APACHE II and NISS + APACHE II had higher AUC than that of ISS, NISS or APACHE II alone; and the AUC of NISS + APACHE II was significantly larger than that of ISS + APACHE II (all P < 0.05). NISS + APACHE II showed the largest AUC in death prediction of severe trauma patients. The cut-off value, sensitivity, specificity, positive predict value (+PV), negative predict value (-PV), positive likelihood ratio (+LR), negative likelihood ratio (-LR), and Youden index of NISS + APACHE II, which had the greatest AUC, were 56, 75.2%, 82.0%, 58.1%, 90.9%, 4.17, 0.30, and 0.572, respectively. Conclusion: The combination of anatomic scoring system and physiological scoring system is better than single scoring system for death prediction in patients with severe trauma in ICU, and it may be considered to be a new method for early identification of death risk in patients with severe trauma. © 2015 Chin Crit Care Med.

Xu H.,Chongqing Medical University
Molecular neurobiology | Year: 2013

Granule cell migration influences the laminar structure of the cerebellum and thereby affects cerebellum function. Bergmann glia are derived from radial glial cells and aid in granule cell radial migration by providing a scaffold for migration and by mediating interactions between Bergmann glia and granule cells. In this review, we summarize Bergmann glia characteristics and the mechanisms underlying the effect of Bergmann glia on the radial migration of granule neurons in the cerebellum. Furthermore, we will focus our discussion on the important factors involved in glia-mediated radial migration so that we may elucidate the possible mechanistic pathways used by Bergmann glia to influence granule cell migration during cerebellum development.

Cao N.,Chongqing Medical University
Molecular neurobiology | Year: 2013

Myelination by oligodendrocytes facilitates rapid nerve conduction. Loss of oligodendrocytes and failure of myelination lead to nerve degeneration and numerous demyelinating white matter diseases. N-methyl-D-aspartate (NMDA) receptors, which are key regulators on neuron survival and functions, have been recently identified to express in oligodendrocytes, especially in the myelin sheath. NMDA receptor signaling in oligodendrocytes plays crucial roles in energy metabolism and myelination. In the present review, we highlight the subcellular location-specific impairment of excessive NMDA receptor signaling on oligodendrocyte energy metabolism in soma and myelin, and the mechanisms including Ca(2+) overload, acidotoxicity, mitochondria dysfunction, and impairment of respiratory chains. Conversely, physiological NMDA receptor signaling regulates differentiation and migration of oligodendrocytes. How can we use above knowledge to treat excitotoxic oligodendrocyte loss, congenital myelination deficiency, or postnatal demyelination? A thorough understanding of NMDA receptor signaling-mediated cellular events in oligodendrocytes at the pathophysiological level will no doubt aid in exploring effective therapeutic strategies for demyelinating white matter diseases.

Asavarut P.,Imperial College London | Zhao H.,Imperial College London | Gu J.,Chongqing Medical University | Ma D.,Imperial College London
Acta Anaesthesiologica Taiwanica | Year: 2013

HMGB1 is a chromosome-binding protein that also acts as a damage-associated molecular pattern molecule. It has potent proinflammatory effects and is one of key mediators of organ injury. Evidence from research has revealed its involvement in the signaling mechanisms of Toll-like receptors and the receptor for advanced glycation end-products in organ injury. HMGB1-mediated organ injuries are acute damage including ischemic, mechanical, allograft rejection and toxicity, and chronic diseases of the heart, kidneys, lungs, and brain. Strategies against HMGB1 and its associated cellular signal pathways need to be developed and may have preventive and therapeutic potentials in organ injury. Copyright © 2013, Taiwan Society of Anesthesiologists. Published by Elsevier Taiwan LLC. All rights reserved.

Zhang B.,Chinese University of Hong Kong | Chen J.,Chongqing Medical University | Cheng A.S.L.,Chinese University of Hong Kong | Ko B.C.B.,Hong Kong Polytechnic University
PLoS ONE | Year: 2014

Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase that is implicated in plethora of biological processes, including metabolism, aging, stress response, and tumorigenesis. Telomerase (TERT) is essential for telomere maintenance. Activation of TERT is considered a crucial step in tumorigenesis, and therefore it is a potential therapeutic target against cancer. We have recently found that SIRT1 expression is highly elevated in hepatocellular carcinoma, and the depletion of SIRT1 leads to substantial reduction in TERT mRNA and protein expression. However, the underlying molecular mechanism of SIRT1-dependent TERT expression remains uncharacterized. Here, we elucidated if SIRT1 regulates TERT expression via transcriptional, epigenetic and post-transcriptional mechanisms. We report that depletion of SIRT1 does not lead to significant change in transcriptional activity and CpG methylation patterns of the TERT promoter, nor does it affect mRNA stability or 3′-UTR regulation of TERT. Intriguingly, depletion of SIRT1 is associated with substantial induction of acetylated histone H3-K9 and reduction of trimethyl H3-K9 at the TERT gene, which are known to be associated with gene activation. Our data revealed that SIRT1 regulates histone acetylation and methylation at the TERT promoter. We postulated that SIRT1 may regulate TERT expression via long-range interaction, or via yet unidentified histone modifications. © 2014 Zhang et al.

Zhuo L.S.,Chongqing Medical University
Zhongguo zhen jiu = Chinese acupuncture & moxibustion | Year: 2011

The theory, methods and ideas of "experiment of progated sensation along meridians (PSM)" were examined in the article through retrieval of ancient medical books, excavating the theory of meridians, the qi of meridians, ying (nutrient) qi, wei (defensive) qi and the related acupuncture techniques. The result shows that PSM is not the reaction of the meridian qi, but the reflection of wei (defensive) qi. Therefore, whether the experiment of PSM revealed with the phenomenon of meridian and all hypothesis based on it or not are still remained as a question. However, although PSM is considered to be related with the wei (defensive) qi, it can not be concluded that the experiment of PSM revealed the function of the wei (defensive) qi.

Yang F.F.,Chongqing Medical University
Genetics and molecular research : GMR | Year: 2012

Single nucleotide polymorphism (SNP)-based genome-wide association studies have revealed that polymorphisms of the ORM1-like 3 (ORMDL3) gene are associated with childhood asthma. We investigated genetic associations of SNPs in and around the ORMDL3 gene with childhood asthma in a Chinese population. Genomic DNA was extracted from peripheral venous blood drawn from 152 subjects with childhood asthma and from 190 control subjects. SNP genotyping was performed with the MassARRAY system (Sequenom) by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Among the six SNPs, only the genotype frequencies of rs7216389 were significantly different between asthmatic children and controls. Asthmatic children had a significantly higher frequency of T alleles [odds ratio (OR) = 1.653, 95% confidence interval (95%CI) = 1.170-2.333] in rs7216389, than controls. The TT genotype of rs7216389 was found to be a significant risk factor for childhood asthma by logistic regression analysis (OR = 1.704, 95%CI = 1.105-2.628). There was no significant association between the TT genotype of rs7216389 and clinical features of childhood asthma. We conclude that the ORMDL3 gene influences childhood asthma and that the TT genotype of the rs7216389 polymorphism is associated with childhood asthma in the Chinese population.

Liu Z.S.,Chongqing Medical University
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2011

To invest the effect and mechanism of matrine on apoptosis of human Burkitt's lymphoma Raji cells. Raji cells were cultured in vitro and treated by different final concentrations (0.4, 0.8, 1.6 mg/mL) of matrine or combined with SB203580 (p38 MAPK inhibitor) before matrine was added, then cocultured for 48 h, cell apoptosis rate was detected by Annexin V-FITC/PI double staining method and the P-p38 MAPK, Fas, FasL protein expresssion of Raji cells were evaluated by Western blot. After cells were treated by matrine (0.4, 0.8, 1.6 mg/mL), the corresponding total apoptosis rate (15.77 +/- 0.53)%, (27.88 +/- 1.52)%, (48.08 +/- 2.87)%, had statistical significance compared with SB203580 groups (11. 48 +/- 0.64)%, (19.34 +/- 0.91)%, (33.98 +/- 1.26)% (P < 0.05 or P < 0.01), and control group (8.78 +/- 0.66)% (P < 0.05 or P < 0.01). As the concentration of matrine gradually increased,the protein expresssion levels of P-p38MAPK, Fas, FasL increased, and decreased after SB203580 were added, the correlation of P-p38MAPK and Fas, FasL was obvious. Matrine can upregulation of Fas and FasL to promote the apoptosis of Raji cells, it may be related to p38MAPK Activation.

Shi J.,Chongqing Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To construct a recombinant adenovirus vector for SH2-DED fusion gene and assess its inhibitory effect on the proliferation of K562 cells. SH2-DED fusion gene and its mutant SH2mt-DED were amplified by splicing PCR and cloned into pAdTrack-CMV plasmid separately to construct the shuttle plasmids pAdT-SD-EGFP and pAdT-SmD-EGFP, respectively. After Pme I digestion, the shuttle plasmids were transformed into ultra-competent pAd5F35-BJ5183 cells to generate defective adenovirus vectors pAd5F35-SD-EGFP and pAd5F35- SmD-EGFP by homologous recombination. The vectors, linearized by Pac I digestion, were further transfected into AD293 cells for packaging and amplified by infecting AD293 cells repeatedly. K562 cells were then infected by the recombinant adenoviruses and the expression of SD was detected by Western blotting. MTT assay and flow cytometry were used to investigate the effect of Ad5F35-SD-EGFP and Ad5F35-SmD-EGFP on the proliferation of K562 cells. The recombinant adenovirus vectors pAd5F35-SD-EGFP and pAd5F35-SmD-EGFP were constructed correctly, with a titer reaching 1.5×10(12) pfu/ml after amplification. Western blotting demonstrated that the target proteins were effectively expressed in transfected K562 cells. MTT assay and flow cytometry showed that transfection with pAd5F35-SD-EGFP resulted in growth inhibition rate of 55.21% in K562 cells, significantly higher than the inhibition rate of 17.95% following transfection with pAd5F35- SmD-EGFP and 7.33% following PBS treatment (P<0.05). The recombinant adenovirus vector Ad5F35-SD-EGFP we constructed can significantly inhibit the proliferation of K562 cells in vitro.

Zhu Z.,Chongqing Medical University
Frontiers of medicine | Year: 2013

Hypertension is a serious public health problem worldwide. More than 60% of the risk factors for hypertension are associated with metabolic disturbances. Metabolic abnormalities increase the risk for hypertension and cause high blood pressure. Improving metabolic disturbances is beneficial for hypertension treatment. Due to the importance of metabolic abnormalities in the pathogenesis of hypertension, we propose a concept of metabolic hypertension. In this review, we discuss and review the clinical types, pathogenesis, risk evaluation and management of metabolic hypertension. Elucidation of the mechanism of metabolic hypertension should facilitate the design of novel pharmacotherapeutics and dedicated antihypertensive manipulations.

Chen G.Q.,Chongqing Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2012

To investigate the effects and possible molecular mechanisms of inhibiting FOXM1 expression on SKOV3 cells by lentiviral vector targeting FOXM1 shRNA. SKOV3 cells were infected by lentiviral vector targeting FOXM1 shRNA with a multiplicity of infection (MOI) of 20, then growth curve of SKOV3 cells was determined by MTT assay, cell cycle was analysed by flow cytometry(FCM), and the expression of mRNA and protein of FOXM1, Cyclin D1, PLK1 by Real time PCR and Western blot. Lentiviral vector targeting FOXM1 shRNA with a multiplicity of infection (MOI) of 20 could significantly inhibit the growth of SKOV3 cells. After infected by lentiviral vector targeting FOXM1 shRNA, the G(0);/G(1); phase cells increased and the S-phase cells decreased, and the expression of mRNA and protein of FOXM1, Cyclin D1, PLK1 of SKOV3 cells were significantly down-regulated. Inhibiting FOXM1 expression has a significantly effect of inhibiting proliferation on SKOV3 cells. Blocking SKOV3 cells in the G(0);/G(1); phase by down-regulating the expression of Cyclin D1, PLK1 protein may be its mechanism.

Luo N.,Chongqing Medical University
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology | Year: 2011

To investigate the relationship between activation of nuclear factor-K-gene binding (NF-κB) and apoptosis induced by matrine(MT) in transplanted tumor of human hepatocellular carcinoma in nude mouse. Tumors were established by injection of hepatocellular carcinoma cell line HepG2 into the back of nude mice. The mice were divided randomly into four groups: Control group, MT group (35 mg/kg), PDTC group (120 mg/kg) and Combination group: PDTC + MT group (120 mg/kg + 35 mg/kg), the reagents were injected peritoneally. The tumor growth curve of nude mice bearing transplanted tumor were observed and the inhibition ratios were evaluated. Apoptosis of carcinoma cells was analyzed by TUNEL. The DNA-binding activity of NF-κB was determined by electrophoretic mobility shift assay (EMSA). Expression of bcl-2 and bax in carcinoma tissue were detected by immunohistochemical method. NF-κB mRNA, bcl-2 mRNA and bax mRNA in carcinoma tissue were detected by RT-PCR. Pyrrolidine dithiocarbamate (PDTC) could enhance the inhibition of matrine on carcinoma proliferation (P < 0.05). The apoptosis and activation of NF-κB in carcinoma cells could be induced by matrine. PDTC significantly suppressed NF-κB activation induced by matrine in carcinoma cells from 93.64 ± 2.95 to 65.78 ± 5.65 (F = 124.754, P < 0.01). Meanwhile, PDTC increased the apoptosis induced by matrine from 55.9% ± 2.8% to 74.3% ± 4.8% (P < 0.05).A positive correlation observed between the expressions of NF-κB and of bcl-2 (Pearson correlation coefficient = 0.983, P < 0.01). Matrine could induce apoptosis and activation of NF-κB in transplanted tumor. PDTC could increase apoptosis in hepatocellular carcinoma cells might be due to the suppression of NF-κB activation and the enhancement of bcl-2 expression.

Liu Y.,Chongqing Medical University
Acta biochimica et biophysica Sinica | Year: 2012

Epithelial-mesenchymal transition (EMT) is an important mechanism of cardiac fibrosis after myocardial infarction (MI). However, it remains unclear whether Snail1, an important regulator of EMT, is involved in cardiac fibrosis. In this study, we explored the expression patterns of Snail1 and a cardiac fibrosis marker-periostin-after MI in mice and then investigated the co-expression between Snail1 and periostin after MI in mice. Our results showed that the mRNA and protein levels of Snail1 and periostin were significantly increased in the infarct area. The Snail1 expression pattern appeared to be parabolic within 14 days after MI. In addition, after MI, all Snail1-positive cells were able to express periostin. These results indicate that Snail1 is mainly activated in the infarct area and is involved in de novo cardiac fibrosis after MI in mice. Thus, it is a potential molecular target in the development of drug interventions for ventricular remodeling after MI.

Hao X.,Chongqing Medical University
Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi | Year: 2013

With the rapid development of biotechnology, we can change the trait of organism using transgenetic technology. In recent years, there are growing interests in the establishment of sperm mediated gene transfer (SMGT) technology as an effective and convenient method to produce transgenic animals. SMGT technology is a transgenetic method, which is easy in operation and does little harm to the cell compared with the other transgenetic methods. In this review, we expound the background, development, mechanism, operation and application of SMGT.

In this study a novel sensitive nanogold particle sensor enhancement based on mixed self-assembled monolayers was explored and used to construct a Surface Plasmon Resonance (SPR) immunosensor to detect Ischemia Modified Albumin (IMA). Compared with a direct binding SPR assay at a limit of detection (LOD) of 100 ng/L, gold nanoparticles (AuNPs) of 10 nm dramatically improved the LOD of IMA to 10 ng/L. Meanwhile, no interfering substance that may lead to false positive results was identified. These results suggested that the SPR biosensor presented superior properties, and provided a simple label-free strategy to increase assay sensitivity for further acute coronary syndrome (ACS) diagnosis.

Ye Y.J.,Chongqing Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2010

To investigate the immune responses and the protection induced by the transgenic Alfalfa (Medicago sativa) containing Eg95-EgA31 fusion gene of Echinococcus granulosus against Eg protoscoleces. The leaf protein was extracted from the transgenic alfalfa by heat-coagulation method, its concentration was prepared for 20 g/L. BALB/c mice were immunized intranasally or orally with the leaf protein once per 3 days for 2 months.At the same time, the leaf protein transfected with pBI-121 blank vector and the normal leaf protein without foreign antigen was served as control. The mice were then challenged intraperitoneally with Eg protoscoleces (50 protoscoleces per mouce)on week 8 after the last vaccination and sacrified on week 24 postinfection to count the rate of reduced hydatid cyst. The specific antibody (IgE, IgG and its subclasses)in the sera collected from the eyeballs was evaluated by ELISA. Splenocytes were separated and cultured in vitro with EgAg, ConA or LPS stimulus.The substes of CD4(+); and CD8(+); T cells were measured by FCM. The splenocytes' proliferation was determined by MTT method.Then the cells were collected, stained by PI and Annexin V-FITC, and analyzed by FCM to get the splenocytes' apoptotic rate.The supernatant was collected to measure the level of IL-12, IL-10, IFN-gamma and TNF-alpha by ELISA. Compared with the control group, The hydatid cyst weight in the oral immunization group decreased by 64.1%; the splenocytes' apoptotic rate got obviously lower than that in the control group; the splenocytes' proliferation increased significantly, the CD4(+); subsets and the ratio of the CD4(+);/CD8(+); did so, and the similar trend about the specific antibody titer and the level of cytokines could be seen in this group. Apoptosis of splenocytes may be inhibited in mice by immunization with the transgenic alfalfa, splenocytes' proliferation and Th1 response can be induced in the mice against the challenge of Eg protoscoleces. CD4(+); T cell and the specific antibody(IgG, IgG2b and IgE) may play important roles in the protection induced by the transgenic alfalfa vaccine.

Zeng C.,Chongqing Medical University | Zeng C.,Shantou Medical College
Clinical Science | Year: 2010

Dual antiplatelet therapy with aspirin and clopidogrel, a P2Y12 antagonist, is a cornerstone for treatment of patients with stroke, peripheral arterial disease and acute coronary artery disease, followed with or without percutaneous coronary intervention. In the present issue of Clinical Science, Giachini and co-workers found that clopidogrel could normalize the increased phenylephrine-induced vascular contraction and the impaired acetylcholine-induced vasodilation in mesenteric arteries from AngII (angiotensin II)-infused Sprague-Dawley rats. This might develop a new area for clopidogrel application; however, whether clopidogrel can improve arterial function in patients with hypertension or diabetes, or if clopidogrel outweighs the beneficial effect of aspirin in those patients, remains an open field for future inquiry. © The Authors Journal compilation © 2010 Biochemical Society.

Bian S.Z.,Chongqing Medical University
The journal of headache and pain | Year: 2013

This prospective and observational study aimed to identify demographic, physiological and psychological risk factors associated with high-altitude headache (HAH) upon acute high-altitude exposure. Eight hundred fifty subjects ascended by plane to 3700 m above Chengdu (500 m) over a period of two hours. Structured Case Report Form (CRF) questionnaires were used to record demographic information, physiological examinations, psychological scale, and symptoms including headache and insomnia a week before ascending and within 24 hours after arrival at 3700 m. Binary logistic regression models were used to analyze the risk factors for HAH. The incidence of HAH was 73.3%. Age (p =0.011), physical labor intensity (PLI) (p =0.044), primary headache history (p <0.001), insomnia (p <0.001), arterial oxygen saturation (SaO2) (p =0.001), heart rate (HR) (p =0.002), the Self-Rating Anxiety Scale (SAS) (p <0.001), and the Epworth Sleepiness Scale (ESS) (p <0.001) were significantly different between HAH and non-HAH groups. Logistic regression models identified primary headache history, insomnia, low SaO2, high HR and SAS as independent risk factors for HAH. Insomnia, primary headache history, low SaO2, high HR, and high SAS score are the risk factors for HAH. Our findings will provide novel avenues for the study, prevention and treatment of HAH.

Wang W.,Wenzhou University | Cai Y.,Wenzhou University | Wu M.,Wenzhou University | Wang K.,Chongqing Medical University | Li Z.,CAS Institute of Botany
Nonlinear Analysis: Real World Applications | Year: 2012

In this paper, we investigate the complex dynamics of a reactiondiffusion S-I model incorporating demographic and epidemiological processes with zero-flux boundary conditions. By the method of Lyapunov function, the global stability of the disease free equilibrium and the epidemic equilibrium was established. In addition, the conditions of Turing instability were obtained and the Turing space in the parameters space were given. Based on these results, we present the evolutionary processes that involves organism distribution and their interaction of spatially distributed population with local diffusion, and find that the model dynamics exhibits a diffusion-controlled formation growth to "holes, holesstripes, stripes, spotsstripes and spots" pattern replication. Furthermore, we indicate that the diseases' spread is getting smaller with R 0 increasing, and the increasing the diffusion of infectious will increase the speed of diseases spreading. Our results indicate that the diffusion has a great influence on the spread of the epidemic and extend well the finding of spatiotemporal dynamics in the epidemic model. © 2012 Elsevier Ltd. All rights reserved.

Riahi R.,University of Arizona | Wang S.,University of Arizona | Long M.,University of Arizona | Long M.,Chongqing Medical University | And 4 more authors.
ACS Nano | Year: 2014

The photothermal effect of plasmonic nanostructures has numerous applications, such as cancer therapy, photonic gene circuit, large cargo delivery, and nanostructure-enhanced laser tweezers. The photothermal operation can also induce unwanted physical and biochemical effects, which potentially alter the cell behaviors. However, there is a lack of techniques for characterizing the dynamic cell responses near the site of photothermal operation with high spatiotemporal resolution. In this work, we show that the incorporation of locked nucleic acid probes with gold nanorods allows photothermal manipulation and real-time monitoring of gene expression near the area of irradiation in living cells and animal tissues. The multimodal gold nanorod serves as an endocytic delivery reagent to transport the probes into the cells, a fluorescence quencher and a binding competitor to detect intracellular mRNA, and a plasmonic photothermal transducer to induce cell ablation. We demonstrate the ability of the gold nanorod-locked nucleic acid complex for detecting the spatiotemporal gene expression in viable cells and tissues and inducing photothermal ablation of single cells. Using the gold nanorod-locked nucleic acid complex, we systematically characterize the dynamic cellular heat shock responses near the site of photothermal operation. The gold nanorod-locked nucleic acid complex enables mapping of intracellular gene expressions and analyzes the photothermal effects of nanostructures toward various biomedical applications. © 2014 American Chemical Society.

Yang P.,Chongqing Medical University
Chinese Journal of Ophthalmology | Year: 2015

Uveitis, as one of the major cause of blindness worldwide, seriously harms patients' vision and quality of life. The social and economic burden caused by uveitis cannot be ignored. Remarkable achievements in basic and clinical uveitis research were gained after decades of unremitting efforts by Chinese ophthalmologists. A number of original results and breakthroughs were achieved in researches on Behcet's disease, VKH syndrome and other important types of disease that lead to blindness. We are integrating the power of the Chinese Ocular Immunology Association, conducting multi-center collaborative research, and establishing the uveitis sample bank of Chinese. We need to train more uveitis specialists in the future, establish diagnostic and treatment practices of different types of uveitis, accelerate the research on main diseases which lead to blindness, further enhance the overall level of uveitis study, and enhance China's research position in international uveitis. Copyright © 2015 by the Chinese Medical Association.

Zhang J.,University of Michigan | Zhang J.,Chongqing Medical University | Ellsworth K.,University of Michigan | Ma P.X.,University of Michigan
Macromolecular Rapid Communications | Year: 2012

We report the synthesis of a hydrophilic copolymer with one polyethylene glycol (PEG) block and one β-cyclodextrin (β-CD) containing block by a "click" reaction between azido-substituted β-CD and propargyl flanking copolymer. 1H NMR study suggested a highly efficient conjugation of β-CD units by this approach. The obtained copolymer was used as a host macromolecule to construct assemblies in the presence of hydrophobic guests. For assemblies containing a hydrophobic polymer, their size can be simply adjusted by simply changing the content of hydrophobic component. By serving as a guest molecule, hydrophobic drugs can also be loaded accompanying the formation of nanoparticles, and the drug payload is releasable. Therefore, the copolymer synthesized herein can be employed as a carrier for drug delivery. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interaction between pneumococcal virulence factors and innate immune receptors triggers host responses via specific signaling pathways after infection. By generating a deficient mutant, we show here that, compared with the wild-type parent strain, glycosyl hydrolase 25 relating to invasion protein (GHIP) mutant strain was impaired in rapid dissemination into vessels and caused less severe inflammation in mice lungs. Further study demonstrated that the lack of this protein in Streptococcus pneumoniae caused an increased susceptibility to whole blood or neutrophils, while this impairment could be recovered by supplementing recombinant GHIP (rGHIP). Additionally, secreted GHIP could be detected in culture medium, and purified protein was able to induce the release of tumor necrosis factor α and interleukin 6 from peritoneal macrophages. Further investigations revealed that the induction of interleukin 6 by this virulence factor depended on the phosphorylation of c-Jun N-terminal kinase and p38 mitogen activated protein kinase and Toll-like receptor 2. Taken together, GHIP, a novel pneumococcal virulence factor, appeared to play a critical role in bacterial survival and the induction of host innate immune response during pneumococcal infection. © 2014 FEBS.

Yi Y.,Chongqing Medical University
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban | Year: 2011

To explore the mechanism of depression treatment by needling at Taichong (LV3) and the correlation between the liver meridian and the frontal lobe. Forty-two patients with moderate depression at the first attack in line with Diagnostic and Statistical Manual of Mental Disorders (4th ed) by American Psychiatric Association were assigned to the fluoxetine group, the needling + fluoxetine group, and the needling group, 14 in each. The therapeutic course for them all was one month. Resting fMRI scanning was performed before and after treatment using 3.0 T magnetic resonance. Data were analyzed using fractional amplitude of low frequency fluctuations (fALFF). Paired t-test was used for comparison. Correlation analysis was performed in the fALFF images after treatment and Hamilton's depression scale. Compared with before treatment, fALFF values in the left frontal lobe (BA6, BA9, BA48), the right frontal lobe (BA4, BA46), the bilateral inferior parietal lobules (BA40, BA48), the precuneus (BA7), the posterior cingutate (BA31), the left occipital lobe (BA17), and the right occipital lobe (BA18) of the needling +fluoxetine group were lowered (P<0.05). fALFF values in the right inferior parietal lobule (BA40) and the right occipital lobe (BA17) of the fluoxetine group were lowered (P<0.05). fALFF values in the left frontal lobe (BA10), the right frontal lobe (BA45), the left occipital lobe (BA19), the right occipital lobe (BA17), the left precuneus (BA7), and the posterior cingutate (BA31) were lowered in the needling group (P<0.05). Hamilton's depression scale was positively correlated with the fALFF value in the left frontal lobe of the needling +fluoxetine group and the needling group, while Hamilton's depression scale was positively correlated with the fALFF value in the left middle frontal gyrus, the left parietal lobe, and the left occipital lobe in the fluoxetine group. Combination of needling and antidepressive agents was superior to needling or antidepressive agents alone. Changes of the frontal lobe functions were correlated with the severity of depression. More extensive correlation existed between the liver meridian and the frontal lobe, which might be the antidepressive mechanism of needling Taichong (LV3).

Objective: To evaluate the efficacy of intermittent pneumatic compression (IPC) in the prevention of venous thromboembolism (VTE) in medical critically ill patients. Methods: A prospective, randomized, controlled study was conducted. One hundred and sixty-two medical critically ill patients were randomly assigned to IPC group and control group by random number table after admitted to intensive care unit (ICU) from June 2008 to June 2010. Patients under anticoagulation medicine therapy were excluded. Patients in the IPC group were treated with IPC to prevent VTE after ICU admission. No measures were taken to prevent VTE in the control group. The rate of VTE Cdeep vein thrombosis (DVT) and pulmonary embolism (PE)], duration of mechanical ventilation (MV), the length of stay in ICU, rate of non-sudden cardiac death and ICU mortality rate and related side-effects of IPC were compared during the subsequent 28 days between two groups. Results: Compared with control group, IPC group was shown to have a significantly lower rate of DVT [3.80% (3/79) vs. 19.28% (16/83), P < 0.01], lower rate of PE [0 (0/79) vs. 9.64% (8/83), P<0.01] and lower rate of non-sudden cardiac death [1.26% (1/79) vs. 7.23% (6/83), P<0.01]. Compared with control group, duration of MV (days: 8±6 vs. 9±8) and length of stay in ICU (days: 9±7 vs. 10±7) were shorter, and the ICU mortality rate of 28 days (24.05% vs. 31.32%) was lower in the IPC group, but they were not statistically significant (all P>0.05). No related side-effects were found in the IPC group. Conclusion: IPC can prevent VTE, and lower the rate of non-sudden cardiac death, and it is safe in medical critically ill patients.

Xiang L.,Chongqing Medical University
Journal of biomedicine & biotechnology | Year: 2012

Efficient osteogenetic differentiation and bone formation from muscle-derived stem cells (MDSCs) should have potential clinical applications in treating nonunion fracture healing or bone defects. Here, we investigate osteogenetic differentiation ability of MDSCs induced by bone morphogenetic protein 9 (BMP9) in vitro and bone formation ability in rabbit radius defects repairing model. Rabbit's MDSCs were extracted by type I collagenase and trypsin methods, and BMP9 was introduced into MDSCs by infection with recombinant adenovirus. Effects of BMP9-induced osteogenetic differentiation of MDSCs were identified with alkaline phosphatase (ALP) activity and expression of later marker. In stem-cell implantation assay, MDSCs have also shown valuable potential bone formation ability induced by BMP9 in rabbit radius defects repairing test. Taken together, our findings suggest that MDSCs are potentiated osteogenetic stem cells which can be induced by BMP9 to treat large segmental bone defects, nonunion fracture, and/or osteoporotic fracture.

Respiratory syncytial virus (RSV) is the most common pathogen responsible for lower respiratory diseases in children. So far, there is no effective treatment or preventative vaccine available for RSV infection, although ribavirin and dexamethasone are commonly prescribed. Resveratrol has been shown to inhibit the replication of several other viruses, thus the effect of resveratrol on RSV-induced inflammatory mediators in 9HTEo cell cultures was evaluated, and possible mechanisms of action were explored and compared with dexamethasone and ribavirin. Incubation with resveratrol resulted in decreased IL-6 production and partial inhibition of RSV replication. Resveratrol treatment also inhibited virus-induced TIR-domain-containing adapter-inducing interferon-β (TRIF) and TANK binding kinase 1 (TBK1) protein expression. These data demonstrate the ability of resveratrol to inhibit cytokine production by RSV in airway epithelial cells, indicating that it might be a therapeutic agent with both anti-inflammatory and antiviral potential for the treatment of RSV infection.

Hou C.L.,Chongqing Medical University
Genetics and molecular research : GMR | Year: 2012

We constructed a plasmid containing a protein transduction domain (PTD) and a human A20 (hA20) gene fragment; the fusion protein was obtained by highly expressing this plasmid in the yeast Pichia pastoris GS115. The plasmid was obtained by adding 9xArg and EcoRI recognition sites to the end of the primer, and 6xHis-Tag and NotI recognition sites to its end. After sequencing, the hA20 gene fragment was inserted into plasmid pPIC9k to construct expression vector pPIC9k-PTD-hA20; then, we transfected GS115 with the vector and induced PTD-hA20 protein expression. We purified protein from the yeast fermentation supernatant using a nickel column. Human umbilical vein endothelial cells (HUVECs) were cultured in high glucose medium (30 mM glucose) and in high glucose medium containing different concentrations of protein. Apoptosis of HUVECs was assayed by TUNEL 72 h later. The biological activity tests indicated that the fusion protein not only passed through the cell membrane freely, but also inhibited apoptosis of HUVECs induced by high glucose levels. We conclude that the fusion protein PTD-hA20 has potential for clinical use.

Wang Z.,Chongqing Medical University
Ultrasonics Sonochemistry | Year: 2015

This perspective, for the first time, proposed the theoretical basis for the minimally-invasive and non-invasive medicine. It sets the goal of medical treatment that is to minimize harm to patients and to maximize the natural self-healing power for fighting against the disease. It took a historical review on the technological developments shaped by the minimally-invasive and non-invasive ideology with a focus on the course of research, development and clinical deployment of the high-intensity focused ultrasound (HIFU) ablation therapy by the Chinese research team. It also summarized the highlights of the "1st Yangtze International Summit of Minimally-invasive and Non-invasive Medicine 2013" and the mandate of the newly inaugurated International Society of the Minimally-invasive and Noninvasive Medicine (ISMINIM). It provides a perspective on the future development of this emerging field and its impact on human civilization. © 2015 Elsevier B.V. All rights reserved.

Hao Y.,Chongqing Medical University
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2012

To analyze the influencing factors of no-reflow phenomenon after reperfusion in patients with chronic limb ischemia associated with acute thrombosis. Between January 2009 and December 2010, 59 patients (67 limbs) with chronic limb ischemia associated with acute thrombosis were treated. According to whether the no-reflow phenomenon occurred or not, the patients were divided into no-reflow group (19 patients, 21 limbs) and reflow group (40 patients, 46 limbs). Logistic regression was used to analyze the roles of ischemia time, ischemia extent, smoking, hypertension, cardiovascular and cerebrovascular disease, diabetes, surgical procedure, platelet count, fibrinogen (FBG), prostaglandin 12 (PGI2), and thromboxane A2 (TXA2) on no-reflow phenomenon after reperfusion. The results of the logistic regression analysis indicated that ischemia time (OR =7.196; 95%CI: 1.679-27.960), ischemia extent (OR = 5.116; 95% CI: 1.399-109.338), smoking (OR = 6.893; 95% CI: 3.704-2 291.003), diabetes (OR = 3.864; 95% CI: 1.009-421.702), PGI2 (OR = 7.985; 95% CI: 1.001-1.043), and TXA2 (OR = 7.643; 95% CI: 1.011-1.065) were the high risk factors of no-reflow phenomenon. The levels of TXA2 and FBG in no-reflow group were significantly increased and the level of PGI2 was decreased, showing significant differences when compared with the reflow group (P < 0.05). However, no significant difference was found in the platelet count between 2 groups (P > 0.05). Ischemia extent and ischemia time are the main influencing factors of no-reflow phenomenon after reperfusion in patients with chronic limb ischemia associated with acute thrombosis, and the patients combined with smoking or diabetes are high risk population of the no-reflow phenomenon. Postoperative patients with no-reflow phenomenon are at a hypercoagulable state in vivo, in which prostacyclin plays an important role.

BACKGROUND:: Dopamine receptors induce natriuresis in kidney. Previous studies have shown interactions between different subtypes of dopamine receptors in renal proximal tubule (RPT) cells. We hypothesize that D3 receptors have an interaction with D4 receptors in RPT cells from normotensive rats (Wistar-Kyoto, WKY) and spontaneously hypertensive rats (SHRs). METHODS:: Immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to examine the expression of D3 and D4 receptors. Na–K-ATPase activity was used to measure the function of receptors. The distribution and colocalization of D3 and D4 receptors were detected by confocal microscopy and co-immunoprecipitation. RESULTS:: D3 receptor agonist PD128907 increased the mRNA and protein expression of D4 receptors in RPT cells from WKY rats, but decreased that from SHRs. In the presence of PLC blocker (U73122, 10−mol/l) or PKC inhibitor 19 -31 (10−mol/l), the up-regulation of D3 receptor on D4 receptor was lost in WKY cells. Moreover, stimulation with PD128907 for 30 minutes decreased D4 receptor degradation in WKY cells, not in SHR cells. D3 and D4 receptors colocalized and co-immunoprecipitated in RPT cells. PD128907 increased co-immunoprecipitation of D3 and D4 receptors in WKY RPT cells, but not in SHR RPT cells. Pre-treatment with D3 receptor agonist also increases D4 receptor mediated inhibitory effect on Na–K-ATPase activity in WKY cells, but not in SHR cells. CONCLUSION:: Renal D3 receptor regulates the expression and function of D4 receptor in RPT cells via PLC /PKC signaling pathway, the loss of this interaction might be involved in the pathogenesis of hypertension. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Tang Z.,Chongqing Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2012

To explore the role of P38 signaling pathway in neonatal rat astrocyte swelling and the expression of aquaporin-4 (AQP4) after oxygen-glucose deprivation (OGD) and recovery (OGD/R). Primarily cultured neonatal rat astrocytes were subject to OGD for 5 h followed by oxygen-glucose recovery in the presence or absence of the P38 inhibitor SB203580 (10 μmol/L). The astrocytes were investigated at 0.5, 2, 8 and 24 h after oxygen-glucose recovery for morphological changes and cell injuries using lactate dehydrogenase (LDH) assay. The expressions of P38, P-P38, and AQP4 mRNAs and proteins in the astrocytes were detected using RT-PCR and Western blotting. OGD/R caused significantly enhanced expression of P-P38 protein, and this effect was blocked by SB203580. AQP4 mRNA and protein expression declined transiently at 0.5 h after OGD and increased gradually to reach the peak level at 8 h (P<0.05). Application of the SB203580 significantly lowered OGD-induced AQP4 mRNA and protein up-regulation (P<0.05). Astrocyte swelling occurred after OGD/R but was obviously lessened by SB203580. LDH release increased markedly after OGD/R, and was attenuated by treatment with SB203580 (P<0.01). P38 signaling pathway participates in astrocyte swelling after OGD/R, and blocking this pathway can attenuate AQP4 up-regulation and ameliorate the cell swelling.

Zhou Q.,Chongqing Medical University
Pulmonary Medicine | Year: 2011

High-altitude pulmonary edema (HAPE) is a life-threatening disease of high altitude that often affects nonacclimatized apparently healthy individuals who rapidly ascend to high altitude. Early detection, early diagnosis, and early treatment are essential to maintain the safety of people who ascend to high altitude, such as construction workers and tourists. In this paper, I discuss various methods and criteria that can be used for the early diagnosis and prediction of HAPE. I also discuss the preventive strategies and options for on-site treatment. My objective is to improve the understanding of HAPE and to highlight the need for prevention, early diagnosis, and early treatment of HAPE to improve the safety of individuals ascending to high altitude. © 2011 Qiquan Zhou.

Sun Y.C.,Chongqing Medical University
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology | Year: 2012

To investigate the changes in Smad 2, 3, 4 and 7 of the transforming growth factor-beta 1 (TGF-b1)/Smad signaling pathways in carbon tetrachloride (CCL4)-induced hepatic fibrosis rats treated with TGF-b1 small interfering (si)RNA. Rats were randomly divided among five groups: non-fibrotic (normal); fibrosis-induced (model); fibrotic treated with 0.125 mg/kg TGF-b1 siRNA; fibrotic treated with 0.250 mg/kg TGF-b1 siRNA; and fibrotic treated with negative control TGF-b1 siRNA. The expression of Smad 2, 3, 4 and 7 was detected by real-time polymerase chain reaction (for mRNA), immunohistochemistry and Western blotting (for protein). The mRNA and protein levels of Smad 2, 3 and 4 were significantly lower in the the fibrotic rats treated with either 0.250 mg/kg or 0.125 mg/kg TGF-b1 siRNA than in the fibrotic model or the negative control TGF-b1 siRNA rats (P less than 0.01). Moreover, the mRNA and protein expression levels of Smad 2, 3 and 4 were significantly lower in the 0.250 mg/kg TGF-b1 siRNA group than in the 0.125 mg/kg group (P less than 0.05). Comparing the 0.250 mg/kg and 0.125 mg/kg TGF-b1 siRNA groups to the model group and the TGF-b1 siRNA negative control group showed significantly increased levels of mRNA and protein expression of Smad 7 (P less than 0.01). In addition, the expression levels of Smad 7 were significantly higher in the 0.250 mg/kg TGF-b1 siRNA group than in the 0.125 mg/kg group (P less than 0.05). siRNA-mediated silencing of TGF-b1 in rats led to significantly reduced expression of Smad 2, 3 and 4, but significantly increased expression of Smad 7. TGF-b1 regulation of Smad signaling molecules may contribute to hepatic fibrosis in rats and represent a target of future therapeutic intervention.

Chen J.,Chongqing Medical University
Annals of biomedical engineering | Year: 2012

Chondrocytes have been widely used as tissue engineered seed cells for repair of focal cartilage lesions in clinic. However, in vivo behaviors of delivered chondrocytes are still poorly understood. In this study, the feasibility of in vivo tracking of superparamagnetic iron oxide nanoparticle (SPIO)-labeled chondrocytes by magnetic resonance imaging (MRI) for articular cartilage repair in minipig model was investigated. Results showed that chondrocytes were efficiently labeled by SPIO at optimal low dosages while maintaining essential cell properties. MRI SET2WI sequence revealed that marked hypointense signal void areas representing the transplanted labeled chondrocytes could be observed for at least 12 weeks. Histochemical staining confirmed the presence of Prussian blue-positive cells and GFP-positive cells at the hypointense signal void areas. These findings provide knowledge on the in vivo tracking of SPIO labeled chondrocytes on cartilage repair following transplantation in minipigs.

He M.,Chongqing Medical University
Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji | Year: 2011

RNA interference (RNAi) is an important topic of epigenetics research in post-genome period. RNAi works as a post-DNA replication regulator for gene expression, and it is related to the occurrence and development of malignant tumors. The most usual participators of RNAi are MicroRNA (miRNA) and small interference RNA (siRNA). This review summarizes the basic theory of miRNA and siRNA, and provides recent progresses of RNAi research on gastric cancer. RNAi analysis and technique not only act as powerful tools for studying gene function and action mechanism, but also have diagnostic and therapeutic potential in gastric cancer, even in all kinds of tumors.

Li L.M.,Chongqing Medical University
Zhen ci yan jiu = Acupuncture research / [Zhongguo yi xue ke xue yuan Yi xue qing bao yan jiu suo bian ji] | Year: 2013

To observe the synchronism difference of brain region activities in response to acupuncture stimulation of Zusanli (ST 36) in healthy volunteer subjects with different acupuncture analgesia sensitivity, so as to study the central factors influencing acupuncture intervention outcomes. Forty-five healthy volunteer subjects with different constitutions (different sensitivities in response to needling stimulation) were divided into insensitive group, normal group and sensitive group (n = 15). The pressure pain threshold (PPT) of the Zusanli (ST 36) region before and after acupuncture stimulation of ST36 was assessed using visual analog scale (VAS). Two weeks later after acupuncture stimulation of ST 36, resting-state fMRI images were acquired by using a nuclear magnetic resonance imaging system and analyzed by using DPARSFV 2.1 software package, software SPM 8 and REST 1.7. The cerebral regional homogeneity (ReHo) of the subjects was then calculated by Resting-State fMRI Data Analysis Toolkit (REST). Compared with pre-acupuncture, PPT levels of the normal and sensitive groups were significantly increased after acupuncture of ST 36 (P < 0.05), and that of the insensitive group had no significant change (P > 0.05). Following acupuncture stimulation of ST 36, the insensitive group only showed a significant decreased ReHo in the left fusiform gyrus, left inferior temporal gyrus, bilateral postcentral gyrus, and left anterior central gyrus. In the normal group, a significantly increased ReHo was found in left brainstem, the right cerebellum posterior lobe, right parahippocampa gyrus, right fusiform gyrus, left angular gyrus, temporal lobe and the left frontal lobe; and a significantly decreased ReHo in the occipital lobes and the right superior temporal gyrus after acupuncture stimulation of ST 36. In the sensitive group, a markedly increased ReHo was found in the left brainstem, bilateral cerebellum posterior lobes, left inferior temporal gyrus, basal ganglia, the left insular lobe, anterior cingutate, frontal lobe, inferior parietal lobule, and the right supplementary motor area, and an obviously decreased ReHo found in the bilateral occipital lobes, fusiform gyrus, posterior central gyrus, the right posterior cingutate, the left temporal lobe and the left paracentral lobule, etc. after acupuncture of ST 36. Constitution-associated needling sensation may be an important influential factor for acupuncture analgesia in normal subjects. The change of ReHo in different cerebral areas is probably responsible for the difference of acupuncture analgesia in different constitution people.

Hu R.-Z.,Chongqing Medical University
Chinese Journal of Biologicals | Year: 2012

Objective: To investigate the effect of over-expression of BRIT1 gene on apoptosis of cervical cancer HeLa cells. Methods: Eukaryotic expression plasmid pcDNA3. 1(-)/BRIT1 was identified by restriction analysis and sequencing and transfected to HeLa cells, using the cells transfected with empty plasmid and those untransfected as control. Forty-eight hours after transfection, the cells were determined for transcription and expression of BRIT1 mRNA by RT-PCR and real-time PCR, for expression of BRIT1 protein by Western blot, and for apoptosis by flow cytometry. Results: Restriction analysis and sequencing proved that recombinant plasmid pcDNA3. 1(-)/BRIT1 was constructed correctly. Both the expressions of BRIT1 mRNA and protein were up-regulated effectively in HeLa cells 48 h after transfection with the constructed plasmid. However, the apoptosis rate of HeLa cells transfected with plasmid pcDNA3. 1(-)/BRIT1[(12.37 ± 0.19)%] was significantly higher than those transfected with empty plasmid[(1.81 ± 0.22)%] and those untransfected [(2.06 ± 0.10)%] (P < 0.05). Conclusion: Over-expression of BRIT1 gene induced the apoptosis of HeLa cells in vitro, which laid a foundation of further study on the role of BRIT1 gene in apoptosis of cervical cancer cells and the relevant mechanism.

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

To investigate the levels and functions of Th17 cells and CD4(+); CD25(+); Foxp3(+); regulate cells(Treg) and explore their role in pathogenesis of primary nephrotic syndrome (PNS) in children. Children with PNS were divided into simple type nephritic syndrome group (SNS) (n = 20), and nephritic type nephritic syndrome group (NNS) (n = 15). 20 healthy subjects were selected as control group. The circulating frequencies of Th17 cells and Treg were measured by FCM. Real-time PCR were used to analyze the mRNA expressions of RORC, IL-23p19 and Foxp3 in peripheral blood mononuclear cells. The serum of IL-1, IL-6, TGF-1 were measured by ELISA. Circulating frequencies of Th17 cells, the mRNA levels of RORC, IL-23p19 and the serum of IL-1, IL-6 were higher in SNS and NNS groups than control group (P < 0.05), and they were higher in NNS group than SNS group (P < 0.05). Compared with control group, the circulating frencencies of Treg cells, the Foxp3mRNA levels and the serum levels of TGF-1 were lower in NNS and SNS groups (P < 0.05), and the circulating frencencies of Treg cells, the Foxp3mRNA levels were lower in NNS group than SNS group (P < 0.05), but NNS and SNS group had no statistical difference in the serum levels of TGF-1 (P > 0.05). Imbalance of Th17 and Treg cells might contribute to the pathogenesis of PNS in children and have associated with clinical presentation, pathological type, glucocorticoid sensitivity and prognosis of the disease.

Zhang Q.,Chongqing Medical University
Chinese Journal of Biologicals | Year: 2012

Objective: To construct the shRNA eukaryotic expression vector for HBx gene of hepatitis B virus (HBV) and screen the interference sequence inhibiting HBx expression effectively. Methods: Three siRNA expression vectors specific for HBx gene were designed and constructed, then identified by restriction analysis and sequencing. HepG2. 2. 15 cells were transfected with the constructed plasmid, then observed for transfection efficacy by fluorescent microscopy and determined for transcription level of HBx mRNA by RT-PCR and expression level of HBx protein by Western blot. Results: The results of restriction analysis and sequencing showed that the plasmids were constructed correctly, and the sequence of inserted gene fragments were consistent with those designed. Both the transcription level of HBx mRNA and expression level of HBx protein in transfected HepG2. 2. 15 cells decreased significantly (each P < 0. 01), indicating that all the three plasmids inhibited the expression of HBx protein in HepG2 .2. 15 cells. However, the inhibiting ability of plasmid shRNA-HBx3 was higher than those of the other two plasmids. Conclusion: The shRNA eukaryotic expression vectors for HBx gene were successfully constructed, of which the one effectively silencing HBx gene was screened. It laid a foundation of further study on onset and progress of HBx infection complicated with fatty degeneration in liver cells.

Zhou W.,Chongqing Medical University
Chinese Journal of Biologicals | Year: 2012

Objective: To investigate the effect of bone marrow mesenchymal stem cells (BMSCs) transplanted on experimental liver fibrosis in rats as well as the relevant mechanism. Methods: BMSCs were isolated and purified from male SD rats by direct adherence method. Thirty female SD rats were divided into normal control, liver model and BMSC groups. The rats in model and BMSC groups were injected s. c. with 40% carbon tetrachloride, 3 times a week, to copy liver fibrosis model. Eight weeks after starting copy of the model, the rats in BMSC group were transplanted twice with 2 × 10 6 BMSCs, at an interval of 3 d. The rats in various groups were killed 12 after starting copy of the model, of which the alanine amiotransferase (ALT), asparatate aminotransferase (AST) and albumin (ALB) content in sera were determined, the pathological change of liver was observed by HE and VG staining, the expressions of type I collagen (Col I ) and glial fibrillary acidic protein (GFAP) in liver were determined by immunohistochemical assay and fluorescent quantitative PCR, and those of transformation growth factor (TGF)β1 and Smad3 mRNAs by fluorescent quantitative PCR. Results: The liver fibrosis of rats was severer in BMSC group than in model group. Compared with those in model group, the ALT and AST levels in BMSC group increased significantly (P < 0. 05), while ALB level decreased significantly (P < 0. 05). Col I and GFAP were expressed in a large quantity in fibers of rats in BMSC group, of which the mRNA and protein levels were significantly higher in BMSC group than in model group (P < 0. 05). The expression levels of TGFβ1 and Smad3 mRNAs were significantly higher in model and BMSC groups than in normal group (P < 0. 05), and in BMSC group than in model group (P < 0.05). Conclusion: The transplantation with BMSCs aggravated the liver fibrosis of rats by up-regulating the expressions of TGFβ1 and Smad3 in TGFβ/Smad signal transduction pathway.

Zhang L.-Y.,Chongqing Medical University
Medical Journal of Chinese People's Liberation Army | Year: 2015

Disastrous blast injury is a rare type injury, but an increasing incidence happened worldwide due to various reasons, often causing mass casualties incidents (MCIs). However, most clinicians have no treatment experience in managing blast injury. The present paper introduces the classification and severity prediction, as well as systematically describes medical rescue strategies for blast injuries, including on-site triage and in-hospital trauma emergency treatments such as trauma emergency care, and emergency care for lung and gastrointestinal tract blast injuries. © 2015 People's Military Medical Press. All rights reserved.

Lu M.,Chongqing Medical University
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2010

Titania and Ag containing nano-hydroxyapatite/polyamide 66 (TiO2-Ag-nHA/PA66) composite bone filling material has good biocompatibility and biological safety. To investigate the antibacterial effect and Ag+ release characteristics of TiO2-Ag-nHA/PA66 composite bone filling material containing different concentrations of Ag+ in vitro. The n-HA/PA66 composite bone filling material A1 (material A1) was prepared by co-polymerization method, and TiO2-Ag-nHA/PA66 composite bone filling materials A2 and A3 (materials A2 and A3) were prepared by the same way containing Ag+ of 0.22wt% and 0.64wt%, respectively, and the TiO2 content was 2.35wt%. The materials A2 and A3 were respectively immersed in 50 mL simulated body fluid (SBF), and Ag+ concentration was measured by atomic absorption spectrometry at 1, 3, 7, 14, 21, and 49 days. The inhibition ring test and colony count method were used to evaluate antibiotic effect against Staphylococcus aureus and Escherichia coli, the anti-adhesion capacity of Staphylococcus aureus and Escherichia coli was observed by scanning electron microscope (SEM). There was no significant difference in the Ag+ concentration between materials A2 and A3 at 1 day and 3 days (P > 0.05); and there were significant differences in the Ag+ concentration between materials A2 and A3 after 7 days (P < 0.05). The inhibition ring diameters of materials A2 and A3 to Staphylococcus aureus and Escherichia coli reached the maximum at 1 day, which were (13.40 +/- 2.88), (9.40 +/- 1.14) mm and (23.60 +/- 1.14), (18.80 +/- 0.84) mm, showing significant difference (P < 0.05) between materials A2 and A3 respectively; and then, the diameter of inhibition ring reduced with the time. The antibacterial effect of materials A2 and A3 against Staphylococcus aureus and Escherichia coli lasted 15, 33 days and 9, 24 days, respectively. No inhibition ring was observed around material A1 all the time. And the inhibitory rates of materials A2 and A3 were 89.74% +/- 3.62%, 94.18% +/- 2.05% and 78.65% +/- 5.64%, 85.96% +/- 2.50%; showing significant differences (P < 0.05) among materials A1, A2, and A3. SEM showed that bacterial adhesion of materials A2 and A3 was obviously fewer than that of material A1. TiO2-Ag-nHA/PA66 composite bone filling material has antibacterial property against Staphylococcus aureus and Escherichia coli, and it has a good release effect in SBF.

Xu Y.,Chongqing Medical University
Cell biology international | Year: 2011

Human LCSCs (lung cancer stem cells) were first isolated from lung cancer patients and cultured using serum-free culture methods. To recreate the intratumoural microenvironment to sustain LCSC growth, autologous intratumoral fibroblasts were used as feeder cells. In this study, we investigated the growth and maintenance of pluripotency in prolonged LCSCs culture on autologous intratumoural fibroblasts. LCSCs isolated from three clinical samples all showed vigorous growth on feeder cells for 16 weeks of continuous cultures with a doubling time of 41-47 h. The cells continued expressing stem cell marker CD133 and remained undifferentiated. Pluripotency was demonstrated by tumour formation in immunodeficient mice. In a feeder-free culture system, growth of LCSCs spheres was retarded and would cease when the diameter reached 100 μm if immediate passage was not performed. Moreover, spontaneous differentiation was more frequently seen in a serum-free culture system. In conclusion, we have successfully established a culture system using autologous intratumoural fibroblast cells as feeder cells for prolonged culture of undifferentiated LCSCs in vitro.

Chen H.,Chinese University of Hong Kong | Ruan Y.C.,Chinese University of Hong Kong | Xu W.M.,Chinese University of Hong Kong | Chen J.,Chinese University of Hong Kong | And 2 more authors.
Human Reproduction Update | Year: 2012

Background: The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated Cl. - and HCO. 3 - conducting channel, mutations of which are known to be associated with male infertility. However, the underlying mechanisms remain elusive. Methods: Literature databases were searched for papers on the topics related to CFTR and male fertility and infertility with relevant keywords. Unpublished data from authors' laboratory were also included for analysis. Results: Clinical evidence shows increased mutation frequency or reduced CFTR expression in men with congenital bilateral absence of vas deferens (CBAVD) or sperm abnormalities, such as azoospermia teratospermia and oligoasthenospermia. Studies on primary rodent Sertoli cells and germ cells, as well as testes from CFTR knockout mice or a cryptorchidism model, yield findings indicating the involvement of CFTR in spermatogensis through the HCO. 3 -/sAC/cAMP/CREB(CREM) pathway and the NF-κB/COX-2/PGE. 2 pathway. Evidence also reveals a critical role of CFTR in sperm capacitation by directly or indirectly mediating HCO. 3 - entry that is essential for capacitation. CFTR is emerging as a versatile player with roles in mediating different signaling pathways pertinent to various reproductive processes, in addition to its long-recognized role in electrolyte and fluid transport that regulates the luminal microenvironment of the male reproductive tract. CONCLUSIONS: CFTR is a key regulator of male fertility, a defect of which may result in different forms of male infertility other than CBAVD. It would be worthwhile to further investigate the potential of developing novel diagnostic and contraceptive methods targeting CFTR. © The Author 2012. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

Zhang L.-Y.,Chongqing Medical University
Chinese Journal of Traumatology - English Edition | Year: 2016

Explosion has become one of the most common causes of death of the combat casualties. I made a comment on one case of autopsy whose cause of death was the accidental denotation of a 355 g rifle grenade and reviewed the clinical approaches and strategies of the blast injury. © 2016 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V.

Long F.-Y.,Chongqing Medical University
Chinese Journal of Biologicals | Year: 2012

Objective: To investigate the expressions of hypoxia-inducible factor-1α (HIF-1α), Twist (a zinc finger transcription inhibitor) and E-cadherin in human breast cancer tissue and their significance. Methods: The expressions of HIF-1α, Twist and E-cadherin in breast cancer tissue specimens from 69 patients receiving no radiotherapy, chemotherapy or hormone therapy before surgery were determined by immunohistochemical assay with SP staining, between which the relationship was analyzed. Results: The positive rates of HIF-1α, Twist and E-cadherin in the breast cancer tissue specimens were 71.01%(49/69), 57.97%(40/69) and 50.72%(35/69) respectively, which were related to the TNM stage and axillary lymph node metastasis (P < 0.05 or P < 0.01), but unrelated to the age of patient as well as size and pathological type of tumor (P > 0.05). The expression of HIF-1α was positively related to that of Twist (r = 0.286, P < 0.05). However, the expression of Twist was negatively related to that of E-cadherin (r = -0.371, P < 0.01). Conclusion: The expressions of HIF-1α, Twist and E-cadherin might be used as markers for monitoring the progress of breast cancer.

Qin Y.,Chongqing Medical University
The Cochrane database of systematic reviews | Year: 2013

Hypercholesterolaemia is a significant risk factor for cardiovascular diseases. Isoflavones may be effective in improving hypercholesterolaemia. To assess the effects of isoflavones for hypercholesterolaemia. We searched the following databases: The Cochrane Library (Issue 9, 2012), MEDLINE, EMBASE, Chinese BioMedical Database and China National Knowledge Infrastructure (all to September 2012). We considered randomized controlled clinical trials in hypercholesterolaemic participants comparing isoflavones versus placebo, or soy isolated protein added with isoflavones versus soy isolated protein alone. Two review authors independently abstracted relevant population and intervention characteristics. We resolved any disagreements through discussion, or if required by a third party. We assessed the risk of bias of trials against key criteria: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting and other sources of bias. We included five randomized trials (208 participants, 104 in the intervention group and 104 in the control group). Interventions ranged from three to six months. Four trials reported results in non-Asian populations published in English. One trial reported results in Chinese people published in Chinese. Overall, the risk of bias of included trials was high or unclear. There were no outcome data on death from any cause, morbidity, complications, health-related quality of life and costs. Two trials reported adverse effects, including gastrointestinal discomfort (bloating and constipation) and an increased number of hot flushes. None of the trials found serious adverse events. There was a slight significant effect on triglycerides in favour of isoflavones when compared with placebo (mean difference (MD) -0.46 mmol/L (95% confidence interval (CI) -0.84 to -0.09; P = 0.02; 52 participants; 2 trials). No statistically significant effects on total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol were shown in favour of isoflavones. We found no evidence for effects of isoflavones on patient-important outcomes or lowering of cholesterol levels in people with hypercholesterolaemia. Our findings have to be interpreted with caution due to high or unclear risk of bias in several risk of bias domains, and low number of participants in trials.

Chang T.,Chongqing Medical University
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2010

To compare the clinical outcomes of the core decompression combined with autologous bone marrow mesenchymal stem cells (BMSCs) transplantation with the isolated core decompression for the treatment of early avascular necrosis of the femoral head (ANFH). From May 2006 to October 2008, 8 patients (16 hips) with early ANFH were treated. There were 7 males and 1 female with an average age of 35.7 years (range, 19-43 years). According to the system of the Association Research Circulation Osseous (ARCO): 4 hips were classified as stage II a, 2 as stage II b, 1 as stage II c, and 1 as stage III a in group A; 2 hips were classified as stage II a, 2 as stage II b, 3 as stage II c, and 1 as stage III a in group B. The average disease course was 1.1 years (range, 4 months to 2 years). The patients were randomly divided into 2 groups according to left or right side: group A, only the core decompression was used; group B, both the core decompression and autologous BMSCs transplantation were used. The Harris score and visual analogue scale (VAS) score were determined, imaging evaluation was carried out by X-rays and MRI pre- and post-operatively. The erythrocyte sedimentation rate, C-reactive protein, liver function, renal function, and immunoglobulin were detected for safety evaluation. All incisions healed by first intention. Eight patients were followed up 12-42 months (23.5 months on average). The clinical symptoms of pain and claudication were gradually improved. The Harris scores and VAS scores of all patients were increased significantly at 3, 6, and 12 months after operation (P < 0.05). There was no significant difference between groups A and B 3 and 6 months after operation (P > 0.05), but there was significant difference between groups A and B 12 months after operation (P < 0.05). The necrosis area of femoral head in groups A and B were 18.13% +/- 2.59% and 13.25% +/- 2.12%, respectively, showing significant difference (P < 0.05). In group A, femoral head collapsed 12 months after operation in 1 case of stage III. No complication of fever, local infection The core decompression and the core decompression combined with BMSCs transplantation are both occurred. effective for the treatment of early ANFH. The core decompression combined with BMSCs transplantation is better than core decompression in the relief of pain and postponing head collapse.

Li H.,Chongqing Medical University
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2012

Prostaglandin E2 (PGE2) production increases in human tendon fibroblasts after the tendon injuries and repetitive mechanical loading in vitro. To analyze the relations between PGE2 and tendinopathy by observing the changes of collagen content and proportion after the Achilles tendon of rabbits is repeatedly exposed to PGE2. Twenty-four Japanese rabbits (aged 3-4 months, weighing 2.0-2.5 kg, and male or female) were equally randomized into 2 groups according to injection dose of PGE2: low dose group (50 ng) and high dose group (500 ng). Corresponding PGE2 (0.2 mL) was injected into the middle segment of the Achilles tendon of hindlimb, the same dose saline into the same site of the other side as controls once a week for 4 weeks or 8 weeks. The Achilles tendons were harvested at 4 and 8 weeks after injection. HE staining was used to observe the cell structure and matrix, and picric acid-sirius red staining to observe the distribution and types of collagen fibers, and transmission electron microscopy was used to measure the density of the unit area and diameter of collagen fibers. HE staining showed that collagen structural damage was observed in low dose and high dose groups. Picric acid-sirius red staining showed that the content of type I collagen significantly decreased while the content of type III collagen significantly increased in experimental side of 2 groups at 4 and 8 weeks after injection when compared with control sides (P < 0.05). The content of type I collagen was significantly lower and the content of type III collagen and ratio of type III to type I were significantly higher in high dose group than in low dose group (P < 0.05). Transmission electron microscopy showed that the collagen fibers density of unit area was significantly lower and the diameter was significantly smaller in high dose and low dose groups than in the controls (P < 0.05), and in high dose group than in low dose group (P < 0.05). Repeat exposure of the Achilles tendon of rabbit to PGE2 can cause the decrease of type I collagen, the increase of type III collagen, the reverse ratio of type I to type III, reduced unit density of collagen fibers, and thinner collagen fibers diameter, which is related with tendinopathy.

Zhang S.,Chongqing Medical University
Proceedings - 2010 International Conference on Computational and Information Sciences, ICCIS 2010 | Year: 2010

This paper discusses the method to find stem resolutions in fuzzy systems in a quick way. Also, this paper explores the application of the method in online fuzzy control systems and at the same time demonstrates the design method to quickly construct economical dynamic fuzzy controller. © 2010 IEEE.

Song K.,Chongqing Medical University
Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi | Year: 2011

Respiration-induced displacements of organs greatly affect the safety and efficiency of high intensity focused ultrasound (HIFU) tumor therapy system. The key to solve this problem is accurate, real-time detection of respiratory signals. The present study gives a new design of an interface compatible non-contacting respiratory signal detection system using the method of irradiating the laser beam onto certain region of the surface of human body that is intensely influenced by the breathing movements (mostly the breast or the dorsum) at a certain angle, and meanwhile using a camera to acquire information from the location of the laser projection. Then we can draw a curve of the location of laser projection versus time base, that is the respiration curve. This respiratory signal detection method is non-contacting, interface compatible and easy to be integrated into the treatment system.

Gong J.,Chongqing Medical University
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2011

To investigate the key parameters of three-dimensional anatomy of the proximal humerus and compare the differences between male and female, and between left and right sides in Chinese by volume rendering technique with multi-slice spiral CT (MSCT) so as to provide a reference for a new prosthesis of the proximal humerus which can adjust to the anatomical characteristics of Chinese. A total of 100 healthy volunteers were collected from Chongqing of China, including 59 males and 41 females with an average age of 40.4 years (range, 21-57 years). The humeral retroversion angle (RA), neck-shaft angle (NSA), medial offset (MO), and posterior offset (PO) were measured by volume rendering technique with MSCT. The average values were compared between male and female and between left and right sides, the correlation of these parameters was also analysed. In 100 volunteers (200 sides), the RA was (19.9 +/- 10.6)degrees, the NSA was (134.7 +/- 3.8)degrees, the MO was (4.0 +/- 1.1) mm, and the PO was (2.6 +/- 1.3) mm. There were significant differences in RA and MO between left and right sides (P < 0.05); there was no significant difference in NSA and PO between left and right sides (P > 0.05). The PO and RA of both sides in male were significantly larger than those in female (P < 0.05); the NSA and MO in male were similar to those in female (P > 0.05). PO was correlated positively with RA (r = 0.617, P = 0.000); MO was not correlated with NSA (r = - 0.124, P = 0.081). Because of significant side differences in RA and MO, and significant gender differences in RA and PO, the differences should be considered in the design of new proximal humeral prosthesis and proximal humerus reconstruction.

Duan W.,City University of Hong Kong | Guo P.,Luzhou Medical College | Gan P.,Chongqing Medical University
PLoS ONE | Year: 2015

The present study aims to examine the relationship between trait resilience and virtues in the context of trauma. A total of 537 participants who attended the preliminary investigation and completed the Life Events Checklist were screened. Of these participants, 142 suffered from personal traumatic experiences in the past year; these individuals were qualified and invited to respond to online questionnaires to assess trait resilience, virtues (i.e., Conscientiousness, Vitality, and Relationship), post-traumatic stress disorder (PTSD) symptoms, and post-traumatic growth (PTG). The following questionnaires were used: Connor-Davidson Resilience Scale-Revised, Chinese Virtues Questionnaire, PTSD Checklist-Specific, and Post-traumatic Growth Inventory-Chinese. Only 95 participants who manifested self-reported PTSD symptoms and PTG were involved in the current analyses. Trauma was positively and significantly correlated with PTSD in the current sample. Results indicated that trait resilience was positively associated with virtues and PTG; by contrast, PTSD scores were negatively but not significantly related to most of these factors. The three virtues contributed to PTG to a greater extent than trait resilience in non-PTSD and PTSD groups. However, trait resilience remained a significant predictor in the PTSD group even when the three virtues were controlled. The relationship between trait resilience and PTG was moderated by PTSD type (non-PTSD group vs. PTSD group). Our results further suggested that trait resilience and virtues were conceptually related but functionally different constructs. Trait resilience and virtues are positively related; thus, these factors contributed variances to PTG in the context of trauma; however, trait resilience is only manifested when virtues are controlled and when individuals are diagnosed as PTSD. Furthermore, implications and limitations of this study are discussed. © 2015 Duan et al.

Zhang Z.,Chongqing Medical University
Journal of Spinal Disorders and Techniques | Year: 2015

STUDY DESIGN:: A retrospective study. OBJECTIVE:: The goal of this retrospective study was to describe the uncommon presentation of neurological deficits in patients with congenital kyphosis of the upper thoracic spine (T1–T4). SUMMARY OF BACKGROUND DATA:: Congenital kyphosis is an uncommon deformity but can potentially lead to spinal cord compression and paraplegia, particularly in type I (failure of formation) deformities. Few reports have described compressive myelopathy associated with congenital kyphosis of the upper thoracic spine. METHODS:: Six patients with congenital kyphosis of the upper thoracic spine, including 2 adults and 4 pediatric patients, developed progressive or sudden onset of paraplegia. Angles of kyphosis ranged from 75 to 120 degrees. Magnetic resonance imaging demonstrated spinal cord thinning and compression at the kyphotic apex in all patients. All patients underwent decompressive and correctional surgery by single-stage posterior vertebral column resection or 2-stage anterior corpectomy fusion and posterior fixation. Neurological status was evaluated using the ASIA impairment classification and the motor score. RESULTS:: Postoperatively, all patients had 25%–80% correction of kyphosis. All patients improved neurologically between 0 and 2 ASIA scales after surgery. Among them, an adolescent patient presenting as acute ASIA A improved to ASIA E within 1 year after surgery. Another adolescent patient deteriorated from preoperative ASIA C to ASIA A in the immediate postoperative period but improved to ASIA D within 1 year after surgery. CONCLUSIONS:: Congenital kyphosis of the upper thoracic spine has a high incidence of compressive myelopathy. Duration from onset of paraplegia to surgical intervention and severity of preoperative paraplegia are 2 key factors in determining neurological prognosis after surgery. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Jiang P.,Chongqing Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2012

To observe the effect of normobaric hyperoxia exposure on the functions of N9 microglia and explore the underlying mechanism of hyperoxia-induced immature brain injury. N9 microglial cells were exposed to 900 ml/L O(2) for 2, 6, 12, 24 or 48 h, and the cell apoptotic rate was assessed using flow cytometry. The intracellular oxidative stress was measured using a fluorescent DCFH-DA probe, and the expression of Toll-like receptor 4 (TLR4) mRNA was detected using RT-PCR. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) concentrations in the supernatant of the cell cultures were tested with ELISA following the exposures. TLR4 protein expression was observed using immunofluorescence staining. Significant cell apoptosis was detected after oxygen exposures for 12-24 h. Accumulation of reactive oxygen species (ROS) were detected after a 2-h exposure. After prolonged hyperoxia exposure, TLR4 expression and IL-1β and TNF-α levels significantly increased in the cells. Hyperoxia exposure activates TLR4 signaling pathway in N9 microglial cells in vitro, leading to massive production of ROS, IL-1β, and TNF-α and thus triggering cell apoptosis.

To identify new genetic risk factors for Vogt-Koyanagi-Harada (VKH) syndrome, we conducted a genome-wide association study of 2,208,258 SNPs in 774 cases and 2,009 controls with follow-up in a collection of 415 cases and 2,006 controls and a further collection of 349 cases and 1,588 controls from a Han Chinese population. We identified three loci associated with VKH syndrome susceptibility (IL23R-C1orf141, rs117633859, Pcombined = 3.42 × 10-21, odds ratio (OR) = 1.82; ADO-ZNF365-EGR2, rs442309, Pcombined = 2.97 × 10-11, OR = 1.37; and HLA-DRB1/DQA1, rs3021304, Pcombined = 1.26 × 10-118, OR = 2.97). The five non-HLA genes were all expressed in human iris tissue. IL23R was also expressed in the ciliary body, and EGR2 was expressed in the ciliary body and choroid. The risk G allele of rs117633859 in the promoter region of IL23R exhibited low transcriptional activation in a cell-based reporter assay and was associated with diminished IL23R mRNA expression in human peripheral blood mononuclear cells.

Fang K.,Sun Yat Sen University | Qian F.,Chongqing Medical University | Chen Y.-Q.,Sun Yat Sen University
Current Molecular Medicine | Year: 2012

Relapse after current treatment is one of the main limitations to the complete cure of leukemia, and a concept that leukemia stem cell (LSC) is the major cause of relapse has been proposed. LSCs are derived from normal hematopoietic stem cells (HSCs), residing at the apex of leukemia cells and hiding in the bone marrow (BM) niche to evade chemotherapy. Novel therapy is strongly needed based on the unique features of LSCs to directly target these cells. MicroRNAs (miRNAs), a class of small non-coding RNAs, are now known to play important roles on cancer stem cell maintenance and differentiation. Because of the ability of miRNAs to inactivate either specific genes or entire gene families, strategies based on differential expression levels of miRNAs in LSCs as dominant activators or suppressors of gene activity have emerged as promising new candidate approaches for eradicating LSCs. In this review, we highlight new findings regarding the roles of miRNAs in LSC maintenance of quiescence repression, self-renewal, surface marker targeting, and the LSCBM niche interaction. We also discuss recent advances and future challenges to use LSC specific miRNAs as potential therapeutic molecules in eradicating LSCs. © 2012 Bentham Science Publishers.

He X.Y.,Chongqing Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To elucidate the role of let-7a-mediated gene regulation in the pathogenesis of lung cancer. Two template DNA sequences were designed based on hsa-let-7a sequence in miRBase database. The let-7a expression construct and a control plasmid, namely pGenesil-let-7a and pGenesil-control, respectively, were generated by cloning the annealed oligonucleotides into pGenesil-1 and then transfected into A549 cells, which were selected by G418 to establish the lung cancer cell lines stably expressing let-7a-GFP and control-GFP. The living cells were counted by MTT assay and cell growth curves were drawn to analyze the cell proliferation. The k-Ras mRNA level was assessed by semi-quantitative RT-PCR, and the expression of k-Ras protein was determined by Western blotting and immunocytochemistry. The recombinant vectors were verified by sequencing. The cell growth curves indicated that the proliferation of the cells transfected with pGenesil- let-7a were inhibited significantly compared with that of cells transfected with pGenesil-control and A549 cells. Semi- quantitative RT-PCR analysis showed that the levels of k-Ras mRNA almost remained unchanged in cells with or without the treatments. Western blotting and immunocytochemistry demonstrated a significant decrease of k-Ras protein levels in cells transfected with pGenesil-let-7a, but not in cells transfected with pGenesil-control, when compared to A549 cells. let-7a over-expression represses the expression of k-Ras protein and significantly inhibits the growth of lung cancer cells.

Yi B.,Chongqing Medical University
Zhonghua nei ke za zhi [Chinese journal of internal medicine] | Year: 2010

To observe the proliferation and phenotype-switching of pulmonary arterial smooth muscle cell (PASMC) induced by hypoxia and interfered by Ad-PKGIα. And to investigate the potential regulative role of PKGIα gene in the molecule mechanism of hypoxia pulmonary vessel remodeling (HPVR). To establish the pure PASMC cultured by tissue-sticking methods. Semi-quantitative reverse transcription and polymerase chain reaction (RT-PCR) and Western blot were used to examine the PKGIα mRNA and protein expression after PASMC were transfected by Ad-PKG. The mRNA and protein expressive change of smooth muscle alpha actin (SM-alpha-actin) determined the degree of cell phenotype-switching. The changes of PASMC proliferation were determined by flow cytometry and 3H-TdR incorporated way. Ad-PKGIα could transfect into PASMC and highly express. Hypoxia down-regulated the expression of SM-alpha-actin protein (44.25 ± 5.34 in normoxia, 32.18 ± 4.19 in 12 h hypoxia condition, 21.90 ± 2.44 in 24 h hypoxia condition, P < 0.05), that could be blocked by the transfection of Ad-PKGIα. Hypoxia could push PASMC mitosis and proliferating (3H-TdR incorporated way: 7570 ± 371 in normoxia, 12,020 ± 831 in 12 h hypoxia condition, 14,924 ± 1491 in 24 h hypoxia condition, P < 0.05), that could be blocked by the transfection of Ad-PKGIα, too. The results suggested that PKGIα signaling pathway might play an important role in the molecule mechanism of HPVR. And PKGIα gene might be a target point of gene therapy.

Xu J.H.,Chongqing Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2010

To investigate the regulatory role of JAK2/STAT3/vimentin signaling pathway on the proliferation and migration of human colon cancer cells. The human colon cancer cell Lovo was treated with Janus kinase inhibitor AG490. The proliferation of Lovo cells was quantified by MTT assay. The migration of Lovo cells was measured with scratch assay. The intracellular phosphorylation STAT3 (P-STAT3) and vimentin protein was detected by Western blot and immunofluorescence. After AG490 treatment, the proliferative ability of Lovo cells decreased as compared with control group (P<0.05). This suppression was dose-independent and time-independent. At 24 hrs after scratching, scratch width in the AG490 group recovered to 20%, lower than that in the control group (60%, P<0.05). After AG490 treatment, the expression of P-STAT3 and vimentin in Lovo cells decreased significantly (P<0.05). JAK2/STAT3/vimentin signaling pathway participates in regulating the proliferation and migration of human colon cancer cells.

Zheng F.,Sun Yat Sen University | Liao Y.-J.,Sun Yat Sen University | Cai M.-Y.,Sun Yat Sen University | Liu Y.-H.,Guangdong Provincial Peoples Hospital | And 9 more authors.
Gut | Year: 2012

Background: Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-124) in hepatocellular carcinoma (HCC). Objective: To determine the status of miR-124 expression and its underlying mechanisms in the pathogenesis of HCC. Methods: The expression levels of miR-124 were first examined in HCC cell lines and tumour tissues by real-time PCR. The in vitro and in vivo functional effect of miR-124 was examined further. A luciferase reporter assay was conducted to confirm target associations. Results: The expression levels of miR-124 were frequently reduced in HCC cells and tissues, and low-level expression of miR-124 was significantly associated with a more aggressive and/or poor prognostic phenotype of patients with HCC (p<0.05). In HCC cell lines, stable overexpression of miR-124 was sufficient to inhibit cell motility and invasion in vitro, and suppress intrahepatic and pulmonary metastasis in vivo. In addition, ectopic overexpression of miR-124 in HCC cells inhibited epithelialemesenchymal cell transition, formation of stress fibres, filopodia and lamellipodia. Further studies showed that miR-124 could directly target the 3′-untranslated region (3′-UTR) of both ROCK2 and EZH2 mRNAs, and suppress their mRNA and protein expressions. These findings suggest that miR-124 plays a critical role in regulating cytoskeletal events and epithelialemesenchymal cell transition and, ultimately, inhibits the invasive and/or metastatic potential of HCC, probably by its direct target on ROCK2 and EZH2 genes. These results provide functional and mechanistic links between the tumour suppressor miRNA-124 and the two oncogenes ROCK2 and EZH2 on the aggressive nature of HCC. Conclusion: These data highlight an important role for miR-124 in the regulation of invasion and metastasis in the molecular aetiology of HCC, and suggest a potential application of miR-124 in prognosis prediction and cancer treatment.

Ji C.Y.,Chongqing Medical University
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery | Year: 2010

The proto-oncogene c-Met was found to express on human laryngeal carcinoma Hep-2 cell line in previous research. In the present study, the author further examined whether inhibition of c-Met by RNA interference (RNAi) might inhibit biologic activity of Hep-2 cell line in vitro and proliferation using a murine laryngeal carcinoma model. RNAi plasmid that can express small interfering RNA targeting c-Met or siRNA that did not match any known human coding mRNA(control siRNA plasmid)was designed, constructed, and transfected into Hep-2 cell line by using cationic liposome Lipofectamine2000 as transfecting agent. In vitro, the transfection efficacy was tested by RT-PCR and Western Blot method, then elected the most inhibitive c-Met-siRNA sequence. Cell proliferation, movement and invasion were studied using MTT, cell migration assay and cell invasion assay, respectively. The Hep-2 cells were transplanted into nude mice, then the time of tumor formation and growth were observed. After tumor formation, c-Met-siRNA was given as the anti-tumor therapy. Expression of c-Met, MMP-9 and VEGF were detected by Western Blot method. After the pSilencer2.0/c-Met-shRNA recombinant plasmid transfection into laryngeal carcinoma Hep-2 cells, the expression of mRNA and protein of c-Met decreased significantly in Hep-2 cells. On the 35th day after tumor vaccination, the tumor volume was (138 ± 27) mm 3 in c-Met-siRNA transfection group, Which was diminished significantly in contrast with control group (P < 0.01). The expression of c-Met, MMP-9 and VEGF in the tumor of experiment group was decreased significantly, respectively (P < 0.05). The results indicated that c-Met-siRNA can down-regulate the expression of c-Met and markedly inhibit laryngeal carcinoma Hep-2 cell proliferation, movement and invasion and the growth of transplantation tumor of nude mice. The siRNA expressing plasmid mediated gene therapy might be a new strategy in targeting molecular therapy of cancer of larynx.

Liu H.,Chongqing Medical University
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology | Year: 2010

To explore the effects of insulin on the expression and the regulatory pathway of AQP9 in normal human liver cells. Normal human liver cells L02 were cultured and treated with PI3K inhibitor LY294002, AKT inhibitor A-443654, MAPK inhibitors SB2030580 and insulin at different concentrations respectively. The AQP9 mRNA and protein expressions were detected with semi-quantitative RT-PCR and Western blot respectively. The insulin (100 nmol/L approximately 500 nmol/L) treatment decreased the expression of AQP9 in normal human liver cells (P less than 0.05) concentration dependently, and the expression of AQP9 began to reduce from 3 hours of insulin stimulation (P less than 0.05), especially at insulin treatment for 12 hours (P less than 0.05); Incubated with the selective inhibitor of PI3K (LY294002) and AKT (A-443654), the inhibitory effects of insulin on AQP9 expression decreased (P less than 0.05); but it did not change significantly by blocking the MAPK signaling pathway. The insulin treatment inhibited the expression of AQP9 and the PI3K/akt signal transduction pathway was involved in the mechanism.

Jiang S.,Duke University | Li C.,Duke University | McRae G.,Duke University | Lykken E.,Duke University | And 4 more authors.
Science Signaling | Year: 2014

Methyl CpG binding protein 2 (MeCP2) is an X-linked, multifunctional epigenetic regulator that is best known for its role in the neurological disorder Rett syndrome; however, it is also linked to multiple auto-immune disorders. We examined a potential role for MeCP2 in regulating the responses of CD4+ T cells to stimulation with antigen. MeCP2 was indispensable for the differentiation of naïve CD4+ T cells into T helper type 1 (TH1) and TH17 cells and for TH1- or T H17-mediated pathologies in vitro and in vivo. Loss of MeCP2 in CD4+ T cells impaired the expression of the microRNA (miR) miR-124 and consequently relieved miR-124-mediated repression of the translation of suppressor of cytokine signaling 5 (Socs5) mRNA. The resulting accumulation of SOCS5 inhibited the cytokine-dependent activation of signal transducer and activator of transcription 1 (STAT1) and STAT3, which are necessary for the differentiation of TH1 and TH17 cells, respectively. Upon silencing of MeCP2, primary neurons and astrocytes also failed to respond properly to STAT3-dependent signaling stimulated by neurotrophic factors. Together, these findings suggest that the regulation of STAT3 signaling may represent a common etiology underpinning the roles of MeCP2 in both the nervous and immune systems.

Yang P.F.,Chongqing Medical University
Orthopaedic surgery | Year: 2011

To investigate the effect of ultrasound in the treatment of osteoarthritis of the knee. Methods: Eighty-seven out- and in-patients with osteoarthritis of the knee (15 men and 72 women) underwent ultrasonic therapy from February to October 2010. The patients were randomly assigned to an ultrasound group (Group A) and a placebo group (Group B). Group A was offered ultrasonic therapy while Group B underwent mock treatment. The visual analogue scale (VAS) and Lequesne scores of the two groups before and after treatment were compared. The data were analyzed by normal distribution, Student's t-test and the rank sum test. The means during and after treatment of the VAS and Lequesne efficacy index of the treatment group were calculated and plotted on a bar graph. Single sample analysis of Groups A and B showed VAS efficacy index: mean = 0.3640, P= 0.000; Lequesne efficacy index, median = 0.3080, P= 0.000, and mean = 0.1000, P= 0.000; Lequesne efficacy index, mean = 0.0364, P= 0.024, respectively. Independent samples t test and rank sum test showed significant differences between the two groups, namely P= 0.000 for both the VAS and Lequesne curative effect indexes. The means of the VAS efficacy index of the treatment group increased during and after treatment. The means of the Lequesne efficacy index of the treatment group showed no apparent decrease by 28 days after treatment. Ultrasound treatment significantly alleviates joint symptoms, relieving joint swelling, increasing joint mobility and reducing inflammation, in osteoarthritis patients. © 2011 Tianjin Hospital and Blackwell Publishing Asia Pty Ltd.

Dou L.,Chongqing Medical University
Quintessence international (Berlin, Germany : 1985) | Year: 2013

The aim of this systematic review is to investigate the effect of an additional lingual infiltration on the pulpal anesthesia of mandibular teeth. Prospective clinical trials were searched from Medline, EMBASE, Cochrane Library, Pubmed, SCI, and the China National Knowledge Infrastructure. Papers that met the inclusion criteria were accepted. Data was extracted by two investigators using a designed extraction form. The anesthetic efficacy of an additional lingual infiltration on the pulpal anesthesia of mandibular teeth was analyzed. Seven prospective randomized controlled trials were included. All subjects of these studies were volunteers with healthy pulps, without patients with pulpitis. Compared to buccal infiltration alone, an additional lingual infiltration following buccal infiltration is more likely to achieve a successful pulpal anesthesia in the mandibular incisor area, with a relative risk for success of 2.00 [1.08, 3.72] for 2% lidocaine and 1.32 [1.15, 1.51] for 4% articaine. For mandibular canines and premolars, the additional lingual infiltration following inferior alveolar nerve block did not enhance the anesthetic efficacy. In the mandibular molar area, no significant difference was found after an additional lingual infiltration with either 2% lidocaine or 4% articaine. An additional lingual infiltration following buccal infiltration can enhance the anesthetic efficacy compared with buccal infiltration alone in the mandibular incisor area. For mandibular canines, premolars, and molars, an additional lingual infiltration is not recommended, since no data exist to support such usage. Lingual infiltration of articaine in the mandibular teeth with pulpitis should be studied further.

Xu L.,Chongqing Medical University | Sun F.-Q.,Shanxi Medical University | Wang Z.-H.,Shanxi Medical University
Acta Obstetricia et Gynecologica Scandinavica | Year: 2011

Objective. To assess the efficacy and safety of radical trachelectomy (RT) and radical hysterectomy (RH) for patients with early cervical cancer. Design. Systematic review with meta-analysis. Population. Women who had early cervical cancer. Methods. Prospective controlled clinical trials comparing RT with RH were identified using a predefined search strategy. Recurrence, five-year recurrence-free survival rate, five-year overall survival rate, postoperative mortality, intraoperative and postoperative complications between the two operations were compared by using the methods provided by the Cochrane Handbook for Systematic Reviews of Interventions. Results. Three controlled clinical trials involving 587 participants were included. Meta-analysis showed that there was no significant difference between the two groups in recurrence rate [1.38; 95% confidence interval (CI) 0.58-3.28, p=0.47], five-year recurrence-free survival rate (1.17; 95% CI 0.54-2.53, p=0.69), five-year overall survival rate (0.86; 95% CI 0.30-2.43, p=0.78), postoperative mortality (1.14; 95% CI 0.42-3.11, p=0.80), intraoperative complications (1.66; 95% CI 0.11-25.28, p=0.72), postoperative complications (0.52; 95% CI 0.11-2.48, p=0.41), blood transfusion (0.29; 95% CI 0.06-1.36, p=0.12) and number of harvested lymph nodes. However, RT, compared with RH, reduced blood loss and shortened duration to normal urine residual volume and postoperative hospital stay. Moreover, RT may achieve to normal conception rates, while RH makes patients sterile. Conclusions. Radical trachelectomy has similar efficacy and safety to RH as the surgical treatment for early cervical cancer. Moreover, it reduced blood loss and shortened the duration to normal urine residual volumes and postoperative hospital stay. Radical trachelectomy can be used to treat early stage cervical cancer as an alternative operation for patients who wish to preserve fertility. © 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

Yang X.F.,Chongqing Medical University
Zhonghua er ke za zhi. Chinese journal of pediatrics | Year: 2010

To explore mutation of Cited2 gene coding strand in Chinese patients with congenital heart disease (CHD). DNA was extracted from the blood samples of 120 nonhomologous and various CHD patients and 100 healthy children. The sequence of coding regions of Cited2 was amplified by PCR and compared to those in the GeneBank after sequencing to identify the mutations. The family of the samples who have Cited2 mutations were investigated as well. Clustal W software was applied for conservative analysis of the altered amino acids. Three new mutations of Cited2 coding strand were found in 4 CHD patients. Two point mutations were first identified respectively in two patients, one patient with mirror image dextrocardia and tetralogy of Fallot (c.550 G > A), another with aortic stenosis (c.574 A > G). Apart from this, the same deletion (c.573-578del6) was first detected in another two patients, one with ventricular septal defect and atrial septal defect, the other with aortic stenosis and pulmonary stenosis. All the mutations resulted in the protein changes (p.Gly184Ser; p.Ser192Gly; p.Ser192fs). None of these changes were detected in the control group. This study showed that there are 3 brand-new gene mutations as demonstrated by sequencing of Cited2 gene in Chinese CHD patients with a broad phenotype spectrum. Serine-glycine rich junction (SGJ) is considered as the mutation hot spot. Cited2 mutations may be one of the causes of the development of CHD in human.

Zheng Q.-Y.,The Military General Hospital of Beijing PLA | Jin F.-S.,Chongqing Medical University | Yao C.,Nanjing Medical University | Zhang T.,The Military General Hospital of Beijing PLA | And 2 more authors.
Biochemical and Biophysical Research Communications | Year: 2012

Ursolic acid (UA) has shown the anti-tumor properties against a number of human cancers both in vivo and in vitro, however, its effect in bladder cancer and the corresponding mechanisms of action remain largely unknown. Here we found that UA dose-dependently induced growth inhibition and apoptosis in human bladder cancer T24 cells, and activation of AMP-activated protein kinase (AMPK) may contribute to the process. Our Western-blot results demonstrated a significant AMPK activation after UA treatment in T24 cells. Notably, knockdown of AMPKα by the targeted shRNA largely inhibited UA-induced T24 cell growth inhibition and apoptosis, while an AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) or a constitutively active form of AMPK mimic UA's effect. We found the ceramide level was increased after UA treatment in T24 cells, and UA-induced AMPK activation and T24 cell apoptosis were inhibited by ceramide synthase inhibitor fumonisin B1, and was enhanced by exogenously adding cell permeable short-chain ceramide (C6), suggesting that ceramide might serve as an upstream signal for AMPK activation. Further, activation of AMPK by UA promoted c-Jun N-terminal kinase (JNK) activation, but inhibited mTOR complex 1 (mTORC1) signaling to cause survivin down-regulation. Our study suggests that activation of AMPK by UA contributes to growth inhibition and apoptosis in human bladder cancer cells. © 2012 Elsevier Inc.

Highly charged hydrophilic superparamagnetic Fe3O4 colloidal nanocrystal clusters with an average diameter of 195 nm have been successfully synthesized using a modified one-step solvothermal method. Anionic polyelectrolyte poly(4-styrenesulfonic acid-co-maleic acid) sodium salt containing both sulfonate and carboxylate groups was used as the stabilizer. The clusters synthesized under different experimental conditions were characterized with transmission electron microscopy and dynamic light scattering; it was found that the size distribution and water dispersity were significantly affected by the concentration of the polyelectrolyte stabilizer and iron sources in the reaction mixtures. A possible mechanism involving novel gel-like large molecular networks that confined the nucleation and aggregation process was proposed and discussed. The colloidal nanocrystal clusters remained negatively charged in the experimental pH ranges from 2 to 11, and also showed high colloidal stability in phosphate buffered saline (PBS) and ethanol. These highly colloidal stable superparamagnetic Fe3O4 clusters could find potential applications in bioseparation, targeted drug delivery, and photonics.

Li A.,Chongqing University of Technology | Wang J.,Chongqing University of Technology | Wu M.,Chongqing Medical University | Zhang X.,Chongqing University of Technology | Zhang H.,Chongqing University of Technology
European Journal of Pharmacology | Year: 2015

Proliferation of hepatic stellate cells (HSCs) is vital for the development of fibrosis during liver injury. In this study, we describe that arctigenin (ATG), a major bioactive component of Fructus Arctii, exhibited selective cytotoxic activity via inhibiting platelet-derived growth factor-BB (PDGF-BB)-activated HSCs proliferation and arrested cell cycle at G0/G1 phase, which could not be observed in normal human hepatocytes in vitro. The cyclin-dependent kinase (CDK) 4/6 activities could be strongly inhibited by ATG through down-regulation of cyclin D1 and CDK4/6 expression in early G1 phase arrest. In the ATG-treated HSCs, the expression level of p27Kip1 and the formation of CDK2-p27Kip1 complex were also increased. p27Kip1 silencing significantly attenuated the effect of ATG, including cell cycle arrest and suppression of proliferation in activated HSCs. We also found that ATG suppressed PDGF-BB-induced phosphorylation of Akt and its downstream transcription factor Forkhead box O 3a (FOXO3a), decreased binding of FOXO3a to 14-3-3 protein, and stimulated nuclear translocation of FOXO3a in activated HSCs. Furthermore, knockdown of FOXO3a expression by FOXO3a siRNA attenuated ATG-induced up-regulation of p27Kip1 in activated HSCs. All the above findings suggested that ATG could increase the levels of p27Kip1 protein through inhibition of Akt and improvement of FOXO3a activity, in turn inhibited the CDK2 kinase activity, and eventually caused an overall inhibition of HSCs proliferation. © 2014 Elsevier B.V. All rights reserved.

Schwedt T.J.,Mayo Medical School | Zhou J.,Chongqing Medical University | Dodick D.W.,Mayo Medical School
Headache | Year: 2014

By definition, the neurologic impairments of hemiplegic migraine are reversible. However, a few cases of permanent neurologic deficits associated with hemiplegic migraine have been reported. Herein, we present the case of a patient with permanent impairments because of hemiplegic migraine despite normalization of associated brain magnetic resonance imaging abnormalities. Cases like these suggest the need to consider aggressive prophylactic therapy for patients with recurrent hemiplegic migraine attacks. © 2013 American Headache Society.

Hao M.,Chongqing Medical University
Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi | Year: 2011

In order to find microRNA associated with HBV infection and to explore the mechanism of the infection, first of all, we found in our preliminary study that in HepG2 cells transfected with HBV expression plasmid, miR-122 expression was up-regulated, suggesting that miR-122 was related to the HBV infection. On this basis, in the present study, miR-122 and pCH9-HBV1.1 plasmid were cotransfected into HepG2 cells. Southern blot detection result showed that miR-122 can inhibit HBV replication. Using MiRanda computer software, HBx was predicted to be the target sequence of miR-122; Luciferase reporter gene system and Western blot detection of HBx protein expression changes were further used to verify the HBx expression regulated by miR-122. And finally, it can be speculated that miR-122 may affected HBV replication by regulating the expression of HBx.

Gu W.-J.,Nanjing University | Wu X.-D.,Chongqing Medical University | Wang F.,General Hospital of Shenyang Military Command | Ma Z.-L.,Nanjing University | Gu X.-P.,Nanjing University
Chest | Year: 2016

BACKGROUND: Potential benefits and possible risks associated with ultrasound guidance compared with traditional palpation for radial artery catheterization are not fully understood. METHODS: We searched PubMed, Embase, and the Cochrane Library through July 2015 to identify randomized controlled trials that evaluated ultrasound guidance compared with traditional palpation for radial artery catheterization. Primary outcome was first-Attempt failure. Secondary outcomes included mean attempts to success, mean time to success, and hematoma complications. A random-effects model was used to estimate relative risks (RRs) with 95% CIs. RESULTS: Twelve trials used dynamic two-dimensional (2-D) ultrasound guidance (N = 1,992) and two used Doppler ultrasound guidance (N = 666). Compared with traditional palpation, dynamic 2-D ultrasound guidance was associated with a reduced first-Attempt failure (RR, 0.68; 95% CI, 0.52-0.87). Trial sequential analysis showed that the cumulative z curve crossed the trial sequential monitoring boundary for benefit establishing sufficient and conclusive evidence. Dynamic 2-D ultrasound guidance further reduced mean attempts to success, mean time to success, and hematoma complications. No evidence of publication bias was detected. Compared with traditional palpation, Doppler ultrasound guidance had no benefit on first-Attempt failure (RR, 1.00; 95% CI, 0.87-1.15), which was confirmed by trial sequential analysis as the cumulative z curve entered the futility area. CONCLUSIONS: The use of dynamic 2-D ultrasound guidance for radial artery catheterization decreases first-Attempt failure, mean attempts to success, mean time to success, and the occurrence of hematoma complications. Dynamic 2-D ultrasound guidance is recommended as an adjunct to aid radial arterial catheterization. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Fang J.,Chongqing Medical University
Investigative ophthalmology & visual science | Year: 2013

TLR2, TLR4, TLR8, and TLR9 have been reported to be associated with several autoimmune diseases. The current study aimed to explore whether singe nucleotide polymorphisms (SNPs) of these four genes were associated with ocular Behçet's disease (BD), Vogt-Koyanagi-Harada (VKH) syndrome, acute anterior uveitis (AAU) with or without ankylosing spondylitis (AS), or pediatric uveitis in Han Chinese. Genotyping was performed by PCR-restriction fragment length polymorphism. The first stage study comprised 400 ocular BD patients, 400 VKH syndrome patients, 400 AAU ± AS patients, 400 pediatric uveitis patients and 600 healthy subjects. The second stage included 438 ocular BD patients and 1000 healthy subjects. Allele and genotype frequencies were compared between patients and controls using the χ(2) test. Real-time PCR was used to detect mRNA expression from PBMCs obtained from healthy controls. Levels of TNF-α, IL-6, IL-10, and IL-1beta in culture supernatants were measured by ELISA. In the first stage study, only the frequencies of the rs2289318/TLR2 genotype A and C allele and rs3804099/TLR2 genotype CT were significantly higher in ocular BD patients (Pc = 0.048; Pc = 0.008; Pc = 0.005, respectively) compared with controls. The second stage and combined studies confirmed the association (Pc = 0.001; Pc = 6.89E-06, Pc = 2.426E-06, respectively). TLR2 mRNA expression in PBMCs was increased in healthy carriers of the CC genotype of rs2289318/TLR2 and TT genotype of rs3804099/TLR2 following stimulation with peptidoglycan (PGN; P = 0.028; P = 0.004, respectively). No effect of the various TLR2 rs2289318 and rs3804099 genotypes on the release of TNF-α, IL-6, IL-10, and IL-1beta could be detected. This study provides evidence that the TLR2 gene is involved in the susceptibility to ocular BD.

Zhang D.,Chongqing Medical University | Wang Y.,National Center for Tuberculosis Control and Prevention | Lu J.,Capital Medical University | Pang Y.,National Center for Tuberculosis Control and Prevention
Antimicrobial Agents and Chemotherapy | Year: 2016

The combination of β-lactams and β-lactamase inhibitors has been shown to have potent in vitro activity against multidrug-resistant tuberculosis (MDR-TB) isolates. In order to identify the most potent β-lactam-β-lactamase inhibitor combination against MDR-TB, we selected nine β-lactams and three β-lactamase inhibitors, which belong to different subgroups. A total of 121 MDR-TB strains were included in this study. Out of the β-lactams used herein, biapenem was the most effective against MDR-TB and had an MIC50 value of 8 μg/ml. However, after the addition of clavulanate or sulbactam, meropenem exhibited the most potent anti-MDR-TB activity with an MIC50 value of 4 μg/ml. For meropenem, 76 (62.8%), 41 (33.9%), and 22 (18.2%) of the 121 MDR-TB strains were subjected to a synergistic effect when the drug was combined with sulbactam, tazobactam, or clavulanate, respectively. Further statistical analysis revealed that significantly more strains experienced a synergistic effect when exposed to the combination of meropenem with sulbactam than when exposed to meropenem in combination with tazobactam or clavulanate, respectively (P < 0.01). In addition, a total of 10.7% (13/121) of isolates harbored mutations in the blaC gene, with two different nucleotide substitutions: AGT333AGG and ATC786ATT. For the strains with a Ser111Arg substitution in BlaC, a better synergistic effect was observed in the meropenem-clavulanate and in the amoxicillin-clavulanate combinations than that in a synonymous single nucleotide polymorphism (SNP) group. In conclusion, our findings demonstrate that the combination of meropenem and sulbactam shows the most potent activity against MDR-TB isolates. In addition, the Ser111Arg substitution of BlaC may be associated with an increased susceptibility of MDR-TB isolates to meropenem and amoxicillin in the presence of clavulanate. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Xiao L.,Chongqing Medical University
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2011

To investigate the clinical features of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis (EBV-HLH), to analysis the outcome of HLH-2004 protocol, and to explore the prognostic factors in EBV-HLH patients. The clinical features at onset and outcome of HLH-2004 protocol from 83 pediatric patients with EBV-HLH enrolled from January 2006 to December 2009 in our hospital were analyzed retrospectively. Univariate and multivariate COX regression analysis were used to identify statistically significant prognostic factors. (1) Among the 83 patients, 45 were males and 38 were females. The age of onset ranged from 6 months to 14 years 4 months. 44 patients were treated with HLH-2004, and 3-year overall survival (OS) was (55.8 ± 7.9)%. (2) The most common clinical features of EBV-HLH included high fever, cytopenia, hepatosplenomegaly, and coagulopathy; The respiratory symptoms, angina phlogistic, skin rashes, neurologic abnormality were rare. 97.3% of patients showed an elevation of serum ferritin, liver dysfunction and lipid metabolism disorders was found in most of EBV-HLH patients. 89.0% of patient had hemophagocytosis in bone marrow at diagnosis of EBV-HLH. (3) COX regression analysis revealed that anemia degree, serum albumin < 30 g/L, CD4:CD8 abnormity, NK cell < 3%, treatment protocol were related with the prognosis significantly (P < 0.05). EBV-HLH in pediatric patients has severe clinical feature and poor prognosis. HLH-2004 protocol is an effective treatment for patients with EBV-HLH. Symptomatic treatment can't rescue the patients of EBV-HLH.

Wu X.J.,Chongqing Medical University
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2011

To investigate the relationship between moderate-severe asthma and development in children. A total of 389 children in the state of moderate-severe persistent asthma were enrolled, which were divided into moderate (226 cases) and severe group (163 cases). According to age, each group was divided into three groups: 3-year-old (85 cases and 63 cases), 5-year-old (76 cases and 52 cases) and 7 to 10 year-old (65 cases and 48 cases). Meanwhile, 298 healthy children in the same age group were enrolled as control, of which 3-year-old were 96 cases, 5-year-old were 92 cases and 7 to 10 year-old were 110 cases. Height, weight and lung function were measured respectively. 3-year-old of severe group, the value of height, the value of weight, the percentage of height, the percentage of weight, the SDS of height, the SDS of weight [(98.54 ± 7.75) cm, (14.87 ± 2.46) kg, 50.30% ± 16.31%, 50.27% ± 18.29%, 0.11 ± 0.66, 0.06 ± 0.49, respectively] were lower than the moderate group of the same age group ((103.58 ± 5.48) cm, (16.60 ± 2.21) kg, 65.80% ± 18.54%, 65.10% ± 18.92%, 0.46 ± 0.53, 0.45 ± 0.54, respectively) and the control group ((105.60 ± 6.29) cm, (17.82 ± 2.82) kg, 72.37% ± 11.37%, 71.92% ± 2.82%, 0.66 ± 0.62, 0.66 ± 0.52), the difference was significant (F values were 7.295, 8.034, 15.246, 10.745, 8.026, 10.864, respectively, P < 0.05).5-years of severe group, the value of height, the value of weight, the percentage of height, the percentage of weight, the SDS of height, the SDS of weight ((110.10 ± 7.36) cm, (18.76 ± 3.20) kg, 45.86% ± 18.92%, 41.69% ± 12.50%, -0.95 ± 0.42, -0.23 ± 0.34, respectively) were lower than the moderate group of the same age group ((117.76 ± 6.35) cm, (21.63 ± 2.75) kg, 61.81% ± 20.75%, 61.79% ± 18.92%, 0.36 ± 0.62, 0.38 ± 0.56) and the control group ((119.90 ± 5.78) cm, (22.80 ± 3.07) kg, 68.97% ± 18.59%, 66.27% ± 18.35%, 0.57 ± 0.65, 0.48 ± 0.63), the difference was significant (F values were 8.351, 7.864, 15.037, 13.921, 12.116, 11.725, respectively, P < 0.05).7 to 10 years-old of severe group, the value of height, the value of weight, the percentage of height, the percentage of weight, the SDS of height, the SDS of weight ((123.50 ± 9.52) cm, (23.82 ± 5.72) kg, 45.81% ± 15.51%, 42.63% ± 14.91%, -0.06 ± 0.48, -0.02 ± 0.61, respectively) were lower than the moderate group of the same age group ((129.1 ± 8.41) cm, (26.70 ± 5.72) kg, 66.84% ± 16.09%, 64.07% ± 18.58%, 0.48 ± 0.46, 0.42 ± 0.49) and the control group ((131.87 ± 7.71) cm, (28.06 ± 6.01) kg, 71.44% ± 12.70%, 69.64% ± 16.20%, 0.60 ± 0.43, 0.60 ± 0.51), the difference was significant(F values were 6.136, 6.678, 57.316, 37.893, 37.210, 34.152, respectively, P < 0.05). 3-, 5-, 7 to 10 year-old of moderate group, the value of height, the value of weight, the percentage of height, the percentage of weight, the SDS of height, the SDS of weight dropped compared to the control group of the same age, but no significant difference was found (t values were -2.008, -1.988, -1.810, -1.879, -1.713, -1.844, -1.904, -2.019, -1.605, -1.017, -1.411, -0.713, -1.881, -1.896, -1.746, -1.906, -1.523, -1.864, respectively, P > 0.05). The height and weight of children with severe asthma were lower than those of normal children or with moderate asthma.

Xu X.,University of Pittsburgh | Xu X.,Chongqing Medical University | Vatsyayan J.,University of Pittsburgh | Gao C.,University of Pittsburgh | And 2 more authors.
EMBO Reports | Year: 2010

Eukaryotic translation initiation factor 4E (eIF4E) is the cap-binding protein that binds the 5′ cap structure of cellular messenger RNAs (mRNAs). Despite the obligatory role of eIF4E in cap-dependent mRNA translation, how the translation activity of eIF4E is controlled remains largely undefined. Here, we report that mammalian eIF4E is regulated by SUMO1 (small ubiquitin-related modifier 1) conjugation. eIF4E sumoylation promotes the formation of the active eIF4F translation initiation complex and induces the translation of a subset of proteins that are essential for cell proliferation and preventing apoptosis. Furthermore, disruption of eIF4E sumoylation inhibits eIF4E-dependent protein translation and abrogates the oncogenic and antiapoptotic functions associated with eIF4E. These data indicate that sumoylation is a new fundamental regulatory mechanism of protein synthesis. Our findings suggest further that eIF4E sumoylation might be important in promoting human cancers. © 2010 European molecular biology organization.

Wong C.K.,Chinese University of Hong Kong | Cao J.,Chinese University of Hong Kong | Yin Y.B.,Chongqing Medical University | Lam C.W.K.,Chinese University of Hong Kong | Lam C.W.K.,Macau University of Science and Technology
European Respiratory Journal | Year: 2010

Basophils are the accessory cell type for T-helper (Th)2 induction and initiators in immunoglobulin E-mediated chronic allergic inflammation. Basophils and Th17 cells accumulate at the inflammatory sites, such as the airways of allergic asthmatic patients. We investigated the activation of interleukin (IL)-17A on the primary human basophils/KU812 basophilic cells and primary human bronchial epithelial cells/BEAS-2B bronchial epithelial cells. Cytokines, chemokines, adhesion molecules and intracellular signalling molecules were assayed by ELISA or flow cytometry. Co-culture of bronchial epithelial cells and basophils could significantly induce the release of IL-6, an epithelial inflammatory cytokine, and CCL2, a chemokine for basophils, esosinophils and monocytes. Such induction was synergistically enhanced by IL-17A, and direct interaction between these two cells was necessary for IL-17A-induced IL-6 and CCL2 release. Surface expression of intercellular adhesion molecule-1 on bronchial epithelial cells was also upregulated upon their interaction. The interaction of basophils and bronchial epithelial cells under IL-17A stimulation was differentially regulated by extracellular signal-regulated kinase, c-Jun N-terminal protein kinase, p38 mitogen-activated protein kinase and nuclear factor-κB pathways. These findings suggest a novel immunopathological role of Th17 cells and basophils in allergic asthma through the activation of granulocyte-mediated inflammation initiated by the direct interaction between basophils and bronchial epithelial cells. Copyright©ERS Journals Ltd 2010.

The correct management of multiple-ligament injured knees (MLIKs) remains controversial. This study aimed to summarize the epidemiological features and short-term results of patients treated in our department. Sixty-six patients diagnosed with MLIKs from 2009 to 2011 were enrolled. Relevant patient characteristics and clinical variables were analyzed to characterize the epidemiology. A surgical algorithm based on a knee dislocation classification system and postoperative rating scales, including Lysholm and Tegner rating, as well as joint mobility, stability and radiography were collected for functional evaluation at 2.5-year follow-up. The epidemiological profile demonstrated that 30- to 50-year-old men were at the highest risk. The primary causes were vehicle accidents and falls and most common injury type cruciate combined collateral ligament injuries. Final follow-up analysis comparing operative versus conservative management and surgically treated mild versus severe MLIKs showed significant differences in Lysholm and Tegner scale scores, as well as knee mobility and stability. The therapeutic outcome of MLIKs depends on various clinical variables and a surgical algorithm. Satisfactory restoration of function was acquired in the majority of our surgically treated MLIK cases; however, most patients had not achieved their pre-injury activity levels by the follow-up endpoint. © 2013 Chinese Orthopaedic Association and Wiley Publishing Asia Pty Ltd.

OBJECTIVE:: Intermedin (IMD) is a calcitonin gene-related peptide shown to have a protective effect on myocardial function in ischemia–reperfusion injury. Whether IMD has beneficial effect in severe sepsis and septic shock (and its underlying mechanisms) is not known. METHODS:: We induced septic shock using cecal ligation and puncture (CLP). We focused on the potential beneficial effect of IMD1–53 on cardiac papillary muscle and cardiomyocytes against septic shock and its relationship with protection of cardiac function. RESULTS:: Early (immediately after CLP) and late (12?h after CLP) administration of IMD1–53 (0.5?μg/kg) improved animal survival significantly, increased cardiac contractility and function, and improved tissue perfusion and oxygen delivery. The effect of early administration of IMD1–53 was better than that for late administration. The Rho kinase/TnI and BKCa pathways participated in the protective effect of IMD1–53 on cardiac function in septic rats. An inhibitor of Rho kinase (Y-27632) or a BKCa opener (NS1619) abolished the protective effect of IMD1–53 on cardiac function. IMD1–53 increased expression of Rho kinase in cardiac muscle and inhibited TnI phosphorylation. IMD1–53 inhibited currents in BKCa channels and intracellular calcium concentration in cardiomyocytes. CONCLUSION:: IMD1–53 is beneficial against severe sepsis/septic shock. IMD1–53 can improve cardiac contractility and cardiac function significantly, and then improve tissue perfusion and oxygen delivery. Rho kinase and the BKCa pathway have important roles in these effects. These findings provide a new treatment strategy for severe sepsis with cardiac dysfunction. © 2016 by the Shock Society

OBJECTIVE: To investigate the effect of statins on plaque regression after acute coronary syndrome (ACS). METHODS: We carried out a meta-analysis to assess the change in plaque and plaque components in patients with ACS under statin therapy. This meta-analysis combined data of 1623 participants from eight randomized-controlled trials and seven observational studies. RESULTS: The benefits of high-intensity statin therapy on plaque regression occurred after 6 months [standardized mean difference (SMD): −0.27; 95% confidence interval (CI): −0.43 to −0.12; P=0.0006] and were sustained over 12 months (SMD: −0.14; 95% CI: −0.25 to −0.03; P=0.01). No significant decrease was observed in the plaque volume and percent plaque volume under low-dose statin treatment. After 6 months of intensive statin treatment, the plaque volume reduced significantly in patients whose follow-up LDL cholesterol levels did (SMD: −0.16; 95% CI: −0.29 to −0.03; P=0.02) or did not (SMD: −0.21; 95% CI: −0.32 to −0.09; P=0.0007) decrease to 70 mg/dl or less. There was no significant change in plaque composition volumes, but an increase was found in the percent dense calcium volume of 1.31% (95% CI: 0.55–2.07%; P=0.0007). CONCLUSION: Intensive statin therapy duration over 6 months may be as important as achieved LDL-C of less than or equal to 70 mg/dl in plaque regression following ACS. Intensive statin treatment may lead to an earlier regression compared with low-dose statin therapy. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Zhang C.,Chongqing Medical University
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2012

To investigate the changes of Treg/Th17 cells related transcription factors (FOXP3, RORC) and cytokines (TGF-beta, IL-17) in the peripheral blood in patients with allergic rhinitis. Use visual analogue scale (VAS) to assess the allergic rhinitis severity of patients. Eighteen patients with allergic rhinitis and 12 healthy control subjects were consecutively enrolled. Peripheral blood samples were obtained from all patients and healthy control subjects (after prick test). The mRNA expressions of key transcription factors (RORC, FOXP3) in PBMCs were measured by RT-PCR, and the concentrations of TGF-beta, IL-17 in plasma were measured by ELISA. Patients with moderate/severe persistent rhinitis have a VAS of 8.5 +/- 0.8, and total patients have a VAS of 6.2 +/- 1.6. Compared with healthy control subjects, the mRNA expressions of FOXP3 and the concentrations of TGF-beta in plasma were significantly lower in patients with allergic rhinitis (P < 0.01) while the mRNA expressions of RORC and the concentrations of IL-17 in plasma were significantly higher in allergic rhinitis group (P < 0.01). The imbalance of Treg/Th17 cells existed in allergic rhinitis patients, which may contribute to the proceeding of allergic rhinitis.

Zhu S.J.,Chongqing Medical University
Biochemical and biophysical research communications | Year: 2013

Aquaporin8 (AQP8), a member of the aquaporin (AQP) protein family, is weakly distributed in mammalian brains. Previous studies on AQP8 have focused mainly on the digestive and the reproductive systems. AQP8 has a pivotal role in keeping the fluid and electrolyte balance. In this study, we investigated the expression changes of AQP8 in 75 cases of human brain astrocytic tumors using immunohistochemistry, Western blotting, and reverse transcription polymerase chain reaction. The results demonstrated that AQP8 was mainly distributed in the cytoplasm of astrocytoma cells. The expression levels and immunoreactive score of AQP8 protein and mRNA increased in low-grade astrocytomas, and further increased in high-grade astrocytomas, especially in glioblastoma. Therefore, AQP8 may contribute to the proliferation of astrocytomas, and may be a biomarker and candidate therapy target for patients with astrocytomas. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Liu Y.C.,Chongqing Medical University
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology | Year: 2010

To establish a method for simultaneous detection of HBV resistant mutations associated with three kinds of nucleoside analogues. According to 981 HBV complete sequences in GenBank, two pairs of conserved primers labeled with digoxigenin were synthesized to amplify the region of HBV reverse transcriptase. To detect non-synonymous amino acid substitutions associated with lamivudine, adefovir and entecavir, 26 specific oligonucleotide probes covering ten different codon positions, I169T, V173L/G, L180M, A181T/V, T184G, S202I/G, M204V/I, Q215S, N236T and M250V/I/L were synthesized and immobilized on nylon membranes charged positively. The oligonucleotide probes immobilized on nylon membranes were then hybridized with PCR products labeled with digoxigenin to detect three drug-resistant mutations. In order to observe specificity and accuracy of probes, HBV wild-type, resistant reference strains and patients serums were assayed by reverse hybridization technique, respectively. The specific probes of 10 codon positions related to HBV wild-type and resistant reference strains, including I169T, V173L, L180M, A181T, T184G, S202I, M204V, Q215S, N236T, M250V, were distinguished effectively by reverse hybridization method. The results results of 37 samples applicated the method were in accordance with that Of DNA sequencing. Reverse hybridization technique can be applied to detect HBV resistant mutations associated with Lamivudine, Adefovir and Entecavir rapidly and accurately.

Chen K.,Chongqing Medical University
Zhonghua er ke za zhi. Chinese journal of pediatrics | Year: 2011

To evaluate the effect of vitamin A, vitamin A plus iron and "7 + 1" multiple micronutrient-fortified seasoning powder on iron metabolic homeostasis in preschool children. This was a randomized, controlled and blinded interventional field trial. A total of 226 2 - 7 years old preschool children were recruited from three nurseries in the area, and they were randomly assigned into three different fortified diet groups for 6 months. The subjects in Group I were fortified with vitamin A; those in Group II and III were fortified with vitamin A plus iron and vitamin A plus iron, thiamine, riboflavin, folic acid, niacinamide, zinc and calcium (7 + 1), respectively. The concentration of serum vitamin A was measured by high-performance liquid chromatography (HPLC), serum ferritin (SF) was measured by enzyme-linked immunosorbent assay (ELISA), soluble transferrin receptor (sTfR) was measured by microparticle-enhanced, and hemoglobin (HB) by hemiglobincyanide, the sTfR-SF index (TFR-F index) and total body iron content were computed respectively before and after intervention. Simultaneously, children's demographic data, socio-economic status and eating habits, etc. were investigated by questionnaires. A total of 226 preschool children were included in the study with age ranged from 2 to 7 years with average age (4.0 ± 0.85) (means ± standard deviation). The prevalence of anemia, deficient iron storage, vitamin A deficiency (VAD) and suspect sub-clinical vitamin A deficiency (SSVAD) were 23.5%, 15.0%, 6.3% and 25.9%, respectively. The levels of SF and sTfR significantly decreased after intervention in all groups (χ(2) = 8.3298, χ(2) = 16.1471, χ(2) = 15.1371, χ(2) = 15.1171, χ(2) = 5.2617, χ(2) = 4.8844, P < 0.05) especially in group II and group III for SF (χ(2) = 16.1471, χ(2) = 15.1371, P < 0.05) and group I for sTfR (χ(2) = 15.1171, P < 0.05). No marked change of TFR-F index and total body iron contents was observed in group I (t = 0.1817, t = 1.7736, P > 0.05), while TFR-F index decreased and total body iron contents increased in group II and group III (t = 5.3561, t = 6.5979, t = 11.1663, t = 8.7306, P < 0.05) after intervention. Vitamin A intervention has significant effect on iron storage and mobilization but seldom effect on iron absorption in small intestine. The combination of vitamin A and other micronutrients might be a better intervention for the improvement of iron deficiency for preschool-children.

Hu J.,Fudan University | Qian G.-S.,Chongqing Medical University | Bai C.-X.,Fudan University | Bai C.-X.,Guangzhou University
Cancer | Year: 2015

The incidence and mortality of lung cancer in China have rapidly increased. Lung cancer is the leading cause of cancer death in China, possibly because of the inadequate early diagnosis of lung cancer. Reaching a consensus on early diagnostic strategies for lung cancer in China is an unmet needed. Recently, much progress has been made in lung cancer diagnosis, such as screening in high-risk populations, the application of novel imaging technologies, and the use of minimally invasive techniques for diagnosis. However, systemic reviews of disease history, risk assessment, and patients' willingness to undergo invasive diagnostic procedures also need to be considered. A diagnostic strategy for lung cancer should be proposed and developed by a multidisciplinary group. A comprehensive evaluation of patient factors and clinical findings should be completed before treatment. © 2015 American Cancer Society.

Bo L.,Chongqing Medical University
Zhonghua Shiyan Yanke Zazhi/Chinese Journal of Experimental Ophthalmology | Year: 2016

Retinal anatomic structure and physiology function are very complex. Electroretinogram (ERG) is currently the only objective assessment for retinal function. There are groups of devastating diseases characterized by affecting the inner retinal functions. However, compared with its advantages in evaluating the outer retina function, ERG is less sensitive in judging the inner retinal function. The decrease of sensitivity is mainly associated with the crosstalk between the rod and cone systems in the longer visual signal pathways. In the past twenty years, new recording techniques in ERG analysis including oscillatory potentials, ON-OFF responses, photopic negative responses and scotopic threshold response have been developed. These ERG components are generated from the bipolar cells, amacrine cells or retinal ganglion cells and are becoming novel tools to assess the function of the inner retina. Ophthalmologists should fully understand the clinical significance of these ERG components in assessing inner retinal function to better guide the diagnosis and treatment of retinal diseases. Copyright © 2016 by the Chinese Medical Association.

Yang T.,Chongqing Medical University
Chinese Journal of Biologicals | Year: 2012

Objective: To investigate the method for establishment of neonatal BALB / c mouse model of non-lethal Streptococcus pneumonia infection. Methods: SPF neonatal BALB / c mice were randomly divided into two test and two control groups, 20 for each. The mice in test group 1 were infected once with 10 μl of S. pneumonia by intranasal drip on day 7 after birth at dosages of 10 7, 10 8, 10 9, and 10 10 CFU respectively, while those in control group 1 with 10 μl PBS. However, the mice in test group 2 were infected twice with 10 μl of S. pneumonia by intranasal drip on days 6 and 7 after birth at dosages of 10 7, 10 8, 10 9, and 10 10 CFU respectively, while those in control group 2 with 10 μl PBS. Ten mice in each group were killed 24 h after the last infection, of which the lung tissues were homogenized for bacterial culture and identification, and observed for pathological change by HE staining. The other 10 mice in each group were observed for change of bodyweights within 5 d after infection and survival. Results: The mice infected twice with 10 9 CFU S. pneumonia were quiet, of which the skins were pale and the increases of bodyweights decreased. Pathological examination showed inflammatory change in lung, thickening of alveolar septum and a certain inflammatory cell infiltration around blood vessels and bronchus, most of which were neutrophils. Conclusion: Infection with 10 9 CFU S. pneumonia on days 6 and 7 after birth might be an effective method for establishment of neonatal BALB / c mouse model of non-lethal S. pneumonia infection.

Duan X.,Chongqing Medical University | Kadakia A.R.,University of Michigan
Archives of Orthopaedic and Trauma Surgery | Year: 2012

Recurrence of the deformity is unfortunately a common occurrence following surgical treatment of hallux valgus. The underlying reason for recurrence is multifactorial and includes surgeon's factor, patient's factor, and deformity components that were not addressed at the index procedure. Salvage of recurrence can be challenging for both the patient and the surgeon. Successful treatment requires understanding the underlying reason for the failure of initial treatment and correcting bony alignment, restoring the joint congruity, and balancing soft tissues. We present an algorithmic approach to revision hallux valgus surgery. © 2011 Springer-Verlag.

Liu X.,Duke University | He Y.,Chongqing Medical University | Li F.,Duke University | Huang Q.,Shanghai JiaoTong University | And 3 more authors.
Molecular Cell | Year: 2015

Apoptosis is typically considered an anti-oncogenic process since caspase activation can promote the elimination of genetically unstable or damaged cells. We report that a central effector of apoptosis, caspase-3, facilitates rather than suppresses chemical- and radiation-induced genetic instability and carcinogenesis. We found that a significant fraction of mammalian cells treated with ionizing radiation can survive despite caspase-3 activation. Moreover, this sublethal activation of caspase-3 promoted persistent DNA damage and oncogenic transformation. In addition, chemically induced skin carcinogenesis was significantly reduced in mice genetically deficient in caspase-3. Furthermore, attenuation ofEndoG activity significantly reduced radiation-induced DNA damage and oncogenic transformation, identifying EndoG as a downstream effector of caspase-3 in this pathway. Our findings suggest that rather than acting as a broad inhibitor of carcinogenesis, caspase-3 activation may contribute to genome instability and play a pivotal role in tumor formation following damage. © 2015 Elsevier Inc.

Yang Y.Y.,Chongqing Medical University
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica | Year: 2012

To systematically summarize the monitoring over adverse reactions of proprietary Chinese medicines, in order to provide reference for safe clinical medication. By using Excel and SPSS 17.0 were adopted for summarizing ADR monitoring over Chinese patent medicines and comparatively evaluating the non-proprietary Chinese medicines. There were significant differences in data of different state reports of proprietary Chinese medicines and non-proprietary Chinese medicines (P<0.05). The ratio between the serious ADR of proprietary Chinese medicines and the safety risk of non-proprietary Chinese medicines was 1.057 (95% CI:0.915, 1. 221), suggesting that the safety of proprietary Chinese medicines was not higher than the non-proprietary Chinese; as such medicines as Qingkailing, Xuesaitong and Xiangdan have ranked top five for years in terms of ADR and serious ADR, the drug administration and hygiene system shall take more effective control measures for strengthening the monitoring over rational use of drugs; clinical manifestations of severe ADR of proprietary Chinese medicines were dominated by allergic shock, which could not be effectively prevented and monitored by such means as skin test, therefore, pre-clinical treatment risk-benefit evaluation shall be improved.

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

To observe the distribution of Th17 cells and Foxp3(+);CD4(+);CD25(+); regulatory T cells in peripheral blood of patients with nasal polyposis(NP) and their correlation with clinical patients' condition, and to explore the role of Th17/Treg cell ratio imbalance in pathogenesis of nasal polyposis and significance. The frequencies of Th17 cells and Treg cells were determined in 46 patients with NP and 10 controls by flow cytometry. The 46 patients were divided into two groups according to endoscopy score and CT score: the 1 group (endoscopy score: 2-8 scores; CT score: 3-10 scores, n=23) and the 2 group (endoscopy score: 8-12 scores; CT score: 10-19 scores, n=23). Th17 cells were significantly higher in the blood of patients with NP compared with the control group (P<0.01), and the percentage was higher in the 2 group than the 1 group (P<0.05). The frequency of Treg cells was significantly decreased in patients with NP compared to the control group (P<0.01), whereas the difference between two groups was not significant. The ratio of Th17/Treg cells was highest in the 2 group (P<0.01), lower in the 1 group (P<0.01) and lowest in control subjects, and the differences were also significant between two groups (P<0.05). Furthermore, it was confirmed that the ratio of Th17/Treg positively correlated with endoscopy score and CT score (P<0.01). The imbalance of Th17/Treg cell ratio characterized by increased Th17 cells and decreased Treg cells exists in peripheral blood of NP patients and may play an important role in the onset and development of NP. The degree of Th17/Treg cell imbalance may associate with clinical presentation.

Santamaria M.,University of Navarra | Pardo-Saganta A.,University of Navarra | Alvarez-Asiain L.,University of Navarra | Di Scala M.,University of Navarra | And 3 more authors.
Gastroenterology | Year: 2013

Background & Aims: α1-Antichymotrypsin (α1-ACT), a member of the serpin family (SERPINA3), is an acute-phase protein secreted by hepatocytes in response to cytokines such as oncostatin M. α1-ACT is a protease inhibitor thought to limit tissue damage produced by excessive inflammation-associated proteolysis. However, α1-ACT also is detected in the nuclei of cells, where its activities are unknown. Expression of α1-ACT is down-regulated in human hepatocellular carcinoma (HCC) tissues and cells; we examined its roles in liver regeneration and HCC proliferation. Methods: We measured levels of α1-ACT messenger RNA in human HCC samples and healthy liver tissue. We reduced levels of α1-ACT using targeted RNA interference in human HCC (HepG2) and mouse hepatocyte (AML12) cell lines, and overexpressed α1-ACT from lentiviral vectors in Huh7 (HCC) cells and adeno-associated viral vectors in livers of mice. We assessed proliferation, differentiation, and chromatin compaction in cultured cells, and liver regeneration and tumor formation in mice. Results: Reducing levels of α1-ACT promoted proliferation of HCC cells in vitro. Oncostatin M up-regulated α1-ACT expression and nuclear translocation, which inhibited HCC cell proliferation and activated differentiation of mouse hepatocytes. We identified amino acids required for α1-ACT nuclear localization, and found that α1-ACT inhibits cell-cycle progression and anchorage-independent proliferation of HCC cells. HCC cells that overexpressed α1-ACT formed smaller tumors in mice than HCC cells that did not express the protein. α1-ACT was observed to self-associate and polymerize in the nuclei of cells; nuclear α1-ACT strongly bound chromatin to promote a condensed state that could prevent cell proliferation. Conclusions: α1-ACT localizes to the nuclei of hepatic cells to control chromatin condensation and proliferation. Overexpression of α1-ACT slows the growth of HCC xenograft tumors in nude mice. © 2013 AGA Institute.

Ma B.,Marshall University | Xie J.,Marshall University | Jiang J.,Marshall University | Wu J.,Chongqing Medical University
Biomaterials | Year: 2014

The paper reports the fabrication of sandwich-type scaffolds consisting of radially-aligned nanofibers at the bottom, nanofiber membranes with square arrayed microwells and nanostructured cues at the top, and microskin tissues in between as microskin grafts for use in skin regeneration. This class of nanofiber scaffolds was able to confine the microskin tissues in the square arrayed wells and simultaneously present nanotopographic cues to the cultured NIH 3T3 fibroblasts and primary rat skin cells, guiding and facilitating their migration invitro. More importantly, we demonstrated that the sandwich-type transplants exhibited an even distribution of microskin grafts, greatly improved the 'take' rate of microskin tissues, and promoted re-epithelialization on wound invivo. In addition, the void area in the scaffolds was well suitable for exudate drainage in wound. The sandwich-type scaffolds show great potential as microskin grafts for repairing extensive burn injuries and may provide a good solution for the treatment of acute skin defects and chronic wounds including diabetic ulcer, pressure ulcer, and venous stasis ulcer. © 2013 Elsevier Ltd.

Yang X.-C.,University of Massachusetts Amherst | Yang X.-C.,Chongqing Medical University | Samanta B.,University of Massachusetts Amherst | Agasti S.S.,University of Massachusetts Amherst | And 5 more authors.
Angewandte Chemie - International Edition | Year: 2011

Small but mighty: Current methods for generating oil-in-water emulsions provide nanoparticle-stabilized capsules (NPSCs) that are too large for efficient delivery. Electrostatic and hydrogen-bonding interactions were combined to create stable NPSCs with diameters of around 100-nm. Their potential as delivery vehicles was demonstrated through dye studies with HeLa cells. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Zhang J.,University of Michigan | Zhang J.,Chongqing Medical University | Ma P.X.,University of Michigan
Polymer | Year: 2011

Double hydrophilic copolymers (PEG-b-PCDs) with one PEG block and another block containing β-cyclodextrin (β-CD) units were synthesized by macromolecular substitution reaction. Via a dialysis procedure, complex assemblies with a core-shell structure were prepared using PEG-b-PCDs in the presence of a hydrophobic homopolymer poly(β-benzyl l-aspartate) (PBLA). The hydrophobic PBLA resided preferably in the cores of assemblies, while the extending PEG chains acted as the outer shell. Host-guest interaction between β-CD and hydrophobic benzyl group was found to mediate the formation of the assemblies, where PEG-b-PCD and PBLA served as the host and guest macromolecules, respectively. The particle size of the assemblies could be modulated by the composition of the host PEG-b-PCD copolymer. The molecular weight of the guest polymer also had a significant effect on the size of the assemblies. The assemblies prepared from the host and guest polymer pair were stable during a long-term storage. These assemblies could also be successfully reconstituted after freeze-drying. The assemblies may therefore be used as novel nanocarriers for the delivery of hydrophobic drugs. © 2011 Elsevier Ltd. All rights reserved.

Li J.,University of California at San Francisco | Li J.,Chongqing Medical University | Huang N.F.,Stanford University | Zou J.,University of California at San Francisco | And 5 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2013

Objective-Transdifferentiation of fibroblasts to endothelial cells (ECs) may provide a novel therapeutic avenue for diseases, including ischemia and fibrosis. Here, we demonstrate that human fibroblasts can be transdifferentiated into functional ECs by using only 2 factors, Oct4 and Klf4, under inductive signaling conditions. Approach and Results-To determine whether human fibroblasts could be converted into ECs by transient expression of pluripotency factors, human neonatal fibroblasts were transduced with lentiviruses encoding Oct4 and Klf4 in the presence of soluble factors that promote the induction of an endothelial program. After 28 days, clusters of induced endothelial (iEnd) cells seemed and were isolated for further propagation and subsequent characterization. The iEnd cells resembled primary human ECs in their transcriptional signature by expressing endothelial phenotypic markers, such as CD31, vascular endothelial-cadherin, and von Willebrand Factor. Furthermore, the iEnd cells could incorporate acetylated low-density lipoprotein and form vascular structures in vitro and in vivo. When injected into the ischemic limb of mice, the iEnd cells engrafted, increased capillary density, and enhanced tissue perfusion. During the transdifferentiation process, the endogenous pluripotency network was not activated, suggesting that this process bypassed a pluripotent intermediate step. Conclusions-Pluripotent factor-induced transdifferentiation can be successfully applied for generating functional autologous ECs for therapeutic applications. © 2013 American Heart Association, Inc.

Wu F.,Chongqing Medical University
Journal of the Acoustical Society of America | Year: 2013

The ideal cancer therapy not only induces the death of all localized tumor cells without damage to surrounding normal tissue, but also activates a systemic antitumor immunity. High intensity focused ultrasound (HIFU) has the potential to be such a treatment, as it can non-invasively ablate a targeted tumor below the skin surface, and may subsequently augment host antitumor immunity. This paper is to review increasing pre-clinical and clinical evidence linking antitumor immune response to HIFU ablation, and to discuss the potential mechanisms involved in HIFU-enhanced host antitumor immunity. The seminal studies performed so far indicate that although it is not possible to conclude definitively on the connection between HIFU treatment and antitumor immune response, it is nonetheless important to conduct extensive studies on the subject in order to elucidate the processes involved. © 2013 Acoustical Society of America.

Wang D.,Chongqing Medical University
Annals of the Academy of Medicine Singapore | Year: 2010

Introduction: We prospectively evaluated the staging of benign prostate hyperplasia (BPH) to decide transurethral resection of prostate (TURP) therapeutic modality and the fi nal outcomes in patients with lower urinary tract symptoms (LUTS) suggestive of BPH. Materials and Methods: Male patients above 50 years old presented with LUTS suggestive of BPH were included in this study. The initial assessment included the International Prostatic Symptoms Score (IPSS) and the Quality of Life (QOL) index, digital rectal examination (DRE). Transabdominal ultrasound was done to measure the prostate volume, intravesical prostatic protrusion (IPP) and the post void residual (PVR) urine. BPH was classifi ed according to the degree of IPP using grades 1 to 3. The staging of BPH was performed according to the presence or absence of bothersome symptoms (QOL ≥3) and signifi cant obstruction (PVR >100ml). Patients with stage I BPH with no bothersome symptoms and no signifi cant obstruction were generally observed. Those with stage II BPH, bothersome symptoms but no signifi cant obstruction, received pharmacotherapy in the fi rst instance, and were offered TURP if symptoms persisted or worsened. Patients with signifi cant obstruction, persistent PVR >100ml, irrespective of symptoms would be classifi ed as stage III, and were advised to undergo TURP as an option. Lastly, those with stage IV (complications of BPH) were strongly recommended to undergo TURP. Results: A total of 408 patients were recruited in this study and after a mean follow-up of 30 months (range, 6 to 84), 96 (24%) eventually had TURP. Sixteen(13%), 50(21%), 28(64%) and 2(100%) patients who underwent TURP were initially diagnosed as stage I, II, III and IV, respectively. Eighty-seven (91%) of the 96 patients signifi cantly improved to stage I BPH post TURP. Conclusions: These results showed that the staging of BPH can assist in the tailoring of treatment for patients with LUTS suggestive of BPH, with good outcome in 91% post TURP.

Yang K.,Chongqing Medical University
International journal of nanomedicine | Year: 2011

The purpose of this study was to investigate in-vivo visible imaging of oral squamous cell carcinoma (OSCC) by targeting epidermal growth factor receptor (EGFR) with near-infrared quantum dots. Quantum dots with an emission wavelength of 800 nm (QD800) were conjugated to monoclonal antibodies against EGFR, resulting in the probe designated as QD800-EGFR Ab. OSCC cell line (BcaCD885) expressing high levels of EGFR was transplanted subcutaneously into nude mice cheeks to develop an OSCC animal model. QD800-EGFR Ab containing 100 pmol equivalent of QD800 was intravenously injected into the animal model, and in-situ and in-vivo imaging of cheek squamous cell carcinoma was analyzed at 10 different time points. In-vivo imaging and immunohistochemical examination of the tumors showed that intravenously injected QD800-EGFR Ab probe could bind EGFR expressed on BcaCD885 cells. Fluorescence signals of BcaCD885 cells labeled with QD800-EGFR Ab probe could be clearly detected, and these fluorescence signals lasted for 24 hours. The most complete tumor images with maximal signal-to-noise ratio were observed from 15 minutes to 6 hours after injection of the probe. To the best of the authors' knowledge, this is the first study that has obtained clear in-situ and in-vivo imaging of head and neck cancer by using QD800-EGFR Ab probe. The authors conclude that the combination of near-infrared quantum dots that are highly penetrating for tissues with EGFR monoclonal antibody has promising prospects in in-vivo imaging of OSCC and development of personalized surgical therapies.

Long S.,University of Sichuan | Yang X.,Chongqing Medical University | Liu X.,University of Sichuan | Yang P.,University of Sichuan
PLoS ONE | Year: 2012

Background: The association between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and the susceptibility to cervical lesions was unclear. This study was designed to investigate their precise association using a large-scale meta-analysis. Methods: The previous 16 studies were identified by searching PubMed, Embase and CBM databases. The crude odds ratios and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the MTHFR C677T/A1298C polymorphisms and the susceptibility to the cervical lesions. The subgroup analyses were made on the following: pathological history, geographic region, ethnicity, source of controls and source of DNA for genotyping. Results: Neither of the polymorphisms had a significant association with the susceptibility to the cervical lesions in all genetic models. Similar results were found in the subgroup analyses. No association was found between the MTHFR C677T polymorphism and the cervical lesions in the Asia or the America populations though a significant inverse association was found in the Europe population (additive model: P = 0.006, OR = 0.83, 95% CI = 0.72-0.95; CT vs. CC: P = 0.05, OR = 0.83, 95% CI = 0.69-1.00; TT vs. CC: P = 0.05, OR = 0.73, 95% CI = 0.53-1.00). Interestingly, women with the MTHFR A1298C polymorphisms had a marginally increased susceptibility to invasive cancer (ICC) when compared with no carriers but no statistically significant difference in the dominant model (P = 0.06, OR = 1.21, 95% CI = 0.99-1.49) and AC vs. AA (P = 0.09, OR = 1.21, 95% CI = 0.97-1.51). Conclusions: The MTHFR C677T and A1298C polymorphisms may not increase the susceptibility to cervical lesions. However, the meta-analysis reveals a negative association between the MTHFR C677T polymorphisms and the cervical lesions, especially in the European populations. The marginal association between the MTHFR A1298C polymorphisms and the susceptibility to cervical cancer requires a further study. © 2012 Long et al.

Xiong G.,Chongqing Medical University
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2010

Decoy receptor 3 (DcR3) is a soluble receptor without transmembrane and intracellular sequences in its peptide. It can bind to and inactivate the apoptosis-inducing ligand FasL, LIGHT, and TL1A. The aims of this study are to genotype the two polymorphisms in the promotor of DcR3 in esophageal squamous cell cancer patients and controls and analyze the association between individual genetic variation and susceptibility to esophageal squamous cell carcinoma (ESCC). A total of 444 Chinese ESCC patients and 468 matched cancer-free controls were evaluated for the two single nucleotide polymorphisms (SNPs) in DCR3. Polymorphisms were genotyped using the SNPShot technique. The expression of DCR3 in cancer tissues was detected by reverse transcription-polymerase chain reaction. There were significant differences in the allele's distribution of the two SNPs among ESCC cases and controls (P < 0.01). Compared with the 147TT genotype, the 147CC genotype was associated with significant elevated risk of ESCC (odds ratio, 1.89; 95% confidence interval, 1.30-2.96). The risk of 147CC genotype was more notable (odds ratio, 2.19; 95% confidence interval, 1.32-3.64) in the smokers than in the nonsmokers (odds ratio, 1.25; 95% confidence interval, 0.59-2.69). In the stratification analyses, we also found there was a strong correlation between 147 CC and the clinical TNM stage (P < 0.01). Furthermore, significant difference in DCR3 expression in ESCC tissues was found between subgroups with different 147C/T variant. Our finding suggested that DcR3 promoter polymorphism 147C/T might influence the susceptibility to ESCC in the Chinese Han population, maybe by influencing DcR3 expression.

BACKGROUND:: Non-shockable rhythms represent an increasing proportion of reported cases of out-of-hospital cardiac arrest but with an associated poor prognosis. In the present study, we investigated the effects of hydrogen inhalation on cardiac and neurological function after cardiopulmonary resuscitation and compared the therapeutic benefit with hypothermia in an asphyxial rat model of cardiac arrest. METHODS:: Cardiopulmonary resuscitation was initiated after 5 minutes of untreated asphyxial cardiac arrest. Animals were randomly assigned to three experimental groups immediately following successful resuscitation: ventilation with 2% hydrogen/98% oxygen under normothermia (H2 inhalation), ventilation with 2% nitrogen/98% oxygen under normothermia (Control) and ventilation with 2% nitrogen/98% oxygen under hypothermia (TH). Mixed gas inhalation continued for 1 hour while hypothermia continued for 2?hours. Animals were observed up to 96?hours for assessment of survival and neurologic recovery. RESULTS:: No statistical differences in baseline measurements were observed among groups and all the animals were successfully resuscitated. Serum cardiac troponin T and S100B measured during earlier post-resuscitation period were markedly reduced in both H2 inhalation and hypothermic groups. However, significantly better left ventricular ejection fraction, cardiac work and neurological deficit score were observed in the H2 inhalation group. Ninety-six hours survival rate was significantly higher in H2 inhalation group (75.0%), either compared with TH (45.8%) or compared with Control (33.3%). But there was no statistical difference between TH and Control. CONCLUSIONS:: Small amounts of inhaled hydrogen was superior to mild hypothermia in improving cardiac function and neurological outcome in this asphyxial rat model of cardiac arrest. © 2016 by the Shock Society

Jiang S.,Duke University | Li C.,Duke University | Olive V.,University of California at Berkeley | Lykken E.,Duke University | And 5 more authors.
Blood | Year: 2011

Mir-17-92 encodes 6 miRNAs inside a single polycistronic transcript, the proper expression of which is critical for early B-cell development and lymphocyte homeostasis. However, during the T-cell antigen response, the physiologic function of endogenous miR-17-92 and the roles of the individual miRNAs remain elusive. In the present study, we functionally dissected the miR-17-92 cluster and revealed that miR-17 and miR-19b are the key players controlling Th1 responses through multiple coordinated biologic processes. These include: promoting proliferation, protecting cells from activationinduced cell death, supporting IFN-γ production, and suppressing inducible regulatory T-cell differentiation. Mechanistically, we identified Pten (phosphatase and tensin homolog) as the functionally important target of miR-19b, whereas the function of miR-17 is mediated by TGFβRII and the novel target CREB1. Because of its vigorous control over the Th1 cell-inducible regulatory T cell balance, the loss of miR-17-92 in CD4 T cells results in tumor evasion. Our results suggest that miR-19b and miR-17 could be harnessed to enhance the efficacy of T cell-based tumor therapy. © 2011 by The American Society of Hematology.

Yang C.-X.,Chongqing Medical University
Chinese Journal of Biologicals | Year: 2011

Objective: To investigate the effect of overexpression of intracellular domain of Notch2 gene on proliferation of chronic myeloid leukemia (CML) K562 cells as well as the relevant mechanism. Methods: K562 cells were transfected with plasmid carrying the intracellular domain of Notch2 gene (ICN2), then determined for proliferation level by MTT method, and for cell cycle distribution by flow cytometry. The transcription of full-length mRNA of Notch2 gene was determined by RT-PCR, and the expression of Notch2 protein by Western blot. The transcription levels of mRNAs of downstream target genes Hes1 and Hey1 as well as cell proliferation and apoptosis-associated numb, Bcl-2, NF-κ1 and TGF-β1 were determined by RT-PCR. Results: Compared with those of untransfected K562 cells, the count of transfected cells decreased, while the proliferation was inhibited significantly (P < 0.01); the percentage of K562 cells at G 1 stage 48 h after transfection increased (P < 0.01), while that at S stage decreased (P < 0.01); the transcription levels of Notch2, Hes1 and Hey1 mRNAs (P < 0.01) as well as expression level of Notch2 protein (P < 0.01) increased significantly, while the transcription level of numb mRNA showed no significant change; the expression of Bcl-2 was down-regulated, while those of NF-κB and TGF-β1 were up-regulated. Conclusion: The overexpression of intracellular domain of Notch2 gene inhibited the proliferation of K562 cells by a potential mechanism of up-regulating the expressions of TGF-β1 and NF-κB genes, down-regulating that of Bcl-2 gene, and arresting the cells at G 1 stage.

Zhang L.,University of Miami | Lubin A.,University of Miami | Chen H.,University of Miami | Sun Z.,Chongqing Medical University | Gong F.,University of Miami
Cell Cycle | Year: 2012

Damage-specific DNA-binding protein 2 (DDB2) was first isolated as a subunit of the UV-DDB heterodimeric complex that is involved in DNA damage recognition in the nucleotide excision repair pathway (NER). DDB2 is required for efficient repair of CPDs in chromatin and is a component of the CRL4 DDB2 E3 ligase that targets XPC, histones and DDB2 itself for ubiquitination. In this study, a yeast two-hybrid screening of a human cDNA library was performed to identify potential DDB2 cellular partners. We identified a deubiquitinating enzyme, USP24, as a likely DDB2-interacting partner. Interaction between DDB2 and USP24 was confirmed by co-precipitation. Importantly, knockdown of USP24 in two human cell lines decreased the steady-state levels of DDB2, indicating that USP24-mediated DDB2 deubiquitination prevents DDB2 degradation. In addition, we demonstrated that USP24 can cleave an ubiquitinated form of DDB2 in vitro. Taken together, our results suggest that the ubiquitin-specific protease USP24 is a novel regulator of DDB2 stability. © 2012 Landes Bioscience.

Li Y.,Chongqing Medical University | Li Y.,University of Arizona | Marshall C.M.,University of Arizona | Rees H.C.,University of Arizona | And 3 more authors.
Journal of the International AIDS Society | Year: 2014

Introduction: To assess evidence of an association between intimate partner violence (IPV) and HIV infection among women. Methods: Medline/PubMed, Embase, Web of Science, EBSCO, Ovid, Cochrane HIV/AIDS Group's Specialized Register and Cochrane Central Register of Controlled Trials were searched up to 20 May 2013 to identify studies that examined the association between IPV and HIV infection in women. We included studies on women aged ≥15 years, in any form of sexually intimate relationship with a male partner. Results: Twenty-eight studies [(19 cross-sectional, 5 cohorts and 4 case-control studies) involving 331,468 individuals in 16 countries - the US (eight studies), South Africa (four studies), East Africa (10 studies), India (three studies), Brazil (one study) and multiple low-income countries (two studies)] were included. Results were pooled using RevMan 5.0. To moderate effect estimates, we analyzed all data using the random effects model, irrespective of heterogeneity level. Pooled results of cohort studies indicated that physical IPV [pooled RR (95% CI): 1.22 (1.01, 1.46)] and any type of IPV [pooled RR (95% CI): 1.28 (1.00, 1.64)] were significantly associated with HIV infection among women. Results of cross-sectional studies demonstrated significant associations of physical IPV with HIV infection among women [pooled OR (95% CI): 1.44 (1.10, 1.87)]. Similarly, results of crosssectional studies indicated that combination of physical and sexual IPV [pooled OR (95% CI): 2.00 (1.24, 3.22) and any type of IPV [pooled OR (95% CI): 1.41 (1.16, 1.73)] were significantly associated with HIV infection among women. Conclusions: Available evidence suggests a moderate statistically significant association between IPV and HIV infection among women. To further elucidate the strength of the association between IPV and HIV infection among women, there is a need for high-quality follow-up studies conducted in different geographical regions of the world, and among individuals of diverse racial/cultural backgrounds and varying levels of HIV risks. © 2014 Li Y et al; licensee International AIDS Society.

Kang N.,Chongqing Medical University
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2011

To investigate the correlation of the nuclear factor (NF-kappaB) and laryngocarcinoma circulating tumor cells (CTC), observe nuclear factor inhibitor PDTC on laryngeal cancer CTC and its possible mechanism. In order to establish of laryngocarcinoma nude mice model ,The nude mice inoculated with laryngo carcinoma Hep-2 cells. To 50 nude mice were randomly divided into experimental group (PDTC pretreatment group), the control group (saline group), and Sham group (not inoculated carcinoma cells), tumor inoculated mice were labeled with CK-19 CTC markers, and sacrificed after 8 weeks, then RT-PCR detect CK-19mRNA expression in peripheral blood as to understand the expression of laryngocarcinoma CTC; removed tumor to determine its size, immunohistochemical expression of NF-kappaB in laryngocarcinoma, real-time fluorescence Quantitative PCR detection of laryngocarcinoma VEGF and MMP-9mRNA expression. CTC occurrence and the expression of NF-kappaB was not obviously associated, expression in the CTC-positive laryngeal carcinoma, NF-kappaB-positive rate was 90%, while the expression of negative CTC laryngocarcinoma, NF-kappaB-positive rate was 56.7% (P>0.05), but connected with the activity of NF-kappaB; PDTC can inhibit NF-kappaB activation, reduce the incidence of CTC in laryngocarcinoma nude mice model, PDTC group CTC positive rate of 5%, significantly lower than the control group CTC positive rate of 45% (P<0.01). PDTC can reduce the incidence of CTC in the laryngocarcinoma nude mouse model, its role may benefit from PDTC reduced the ability of laryngocarcinoma metastasis, which may be as PDTC inhibit NF-kappaB activity, thus make VEGF-C and the expression of MMP-9 down, reducing angiogenesis and reduce tumor invasion of the larynx.

Luo C.,Chongqing Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2011

To compare the inflammation between wild BALB/c mice and mice with severe combined immunodeficiency (SCID) with endotoxemia induced by lipopolysaccharide (LPS). Endotoxemia models of wild and SCID mice were established by injecting LPS intraperitoneally. Serum was taken before and 3 h, 6 h, 12 h after injecting LPS, liver and lung were taken 12 h after injecting LPS. Alanine transarninase (ALT), aspartate aminotransferase (AST) and blood urea nitrogen (BUN) levels were measured by automatic biochemical analyzer. Liver and lung inflammation injury were observed by H.E staining. TNF-α, IFN-γ, IL-6 and MCP-1 levels in serum were detected by Cytometric Bead Array (CBA). (1) All of SCID mice (8/8) were dead at 12-24 h after injecting LPS, and only one BALB/c mouse (1/8) was dead. (2) ALT and AST levels of SCID mice 12 h after injecting LPS were higer than those of BALB/c mice(P<0.05), but there was no difference of BUN levels between them. (3) The blind liver and lung pathology scores of SCID mice were higher than those of BALB/c mice (P<0.05). (4) TNF-α, IFN-γ, IL-6 and MCP-1 levels in serum at 3 h, 6 h, 12 h after injecting LPS increased significantly, and the cytokine levels of SCID mice were higher than those of BALB/c mice(P<0.05). SCID mice don't only excessively secrete inflammatory cytokines after injecting LPS, but also lead to more severe endotoxemia and inflammation injury of organs, which are the important cause of mouse death. The above results also show that the adjustment deficiency of adaptive immunoresponse, abnormal augmentation of innate immunoresponse may be an important cause of severe SIRS of endangering life.

Zeng C.H.,Chongqing Medical University
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology | Year: 2011

To observe the effects of curcumin derivative on non-alcoholic steatohepatitis (NASH). 60 SD male rats were randomly divided into 5 groups. The NASH model was induced by high fat diet combined with carbon tetrachloride. These rats were then treated with curcumin and curcumin derivative, saline treating group as control. The serum biochemical parameters and liver histological examinations were observed. The TNF alpha, NF-kappa B and HMG-CoA reductase mRNA transcriptions of liver tissue were detected with RT-PCR. The protein expressions of TNF alpha and NF-kappa B were detected by western blot. Compared with the saline group, A remarkable reduction was observed in serum ALT (U/L), AST (U/L) and TC (mmol/L) in rats treated with curcumin derivatives [(69.20 +/- 27.58) vs (102.43 +/- 47.29), (158.00 +/- 39.15) vs (229.50 +/- 105.20) and (2.08 +/- 0.30) vs (2.58 +/- 1.02), P < 0.05]. The degrees of fibrosis were significantly alleviated; Compared with curcumin group, liver index and serum ALT, AST of curcumin derivative group were also significantly decreased [(4.88 +/- 0.62) vs (5.16 +/- 0.61); (69.20 +/- 27.58) vs (82.5 +/- 33.23); (158.00 +/- 39.15) vs (211.75 +/- 106.30), P < 0.05]; The liver steatosis and inflammation grade were also significantly improved .The gene transcriptions of TNF alpha, NF-kappa B and HMG-CoA reductase in curcumin derivative group were significantly lower than those in curcumin and saline group (P < 0.05). These results indicate that the water-soluble curcumin derivative displays superior bioavailability to the parent curcumin, which can effectively improve the lipid metabolism and delay the progression of hepatic fibrosis in rats with steatohepatitis.

Fang B.,Southwest University | Zhou C.-H.,Southwest University | Rao X.-C.,Chongqing Medical University
European Journal of Medicinal Chemistry | Year: 2010

A series of novel amine-derived bis-azole compounds were designed by the systematical structural modification of Fluconazole and synthesized by a convenient and efficient method, and the antimicrobial activities for all prepared compounds were evaluated in vitro against six representative bacterial strains and two fungal strains. Bioactive results indicated that some synthesized compounds exhibited moderate or even better activities in comparison with the reference drugs. Especially, bis-imidazole 5b and its salts gave significant antibacterial efficacy against all tested bacteria strains including MRSA, while bis-triazoles 4b-c and their corresponding salts exhibited better activities against Candida albicans, Bacillus proteus than standard drugs Fluconazole and Norfloxacin respectively. Unexpectedly, bis-bromides 3a-f presented excellent activities against all tested microbial strains. A series of novel amine-derived bis-azoles were synthesized and evaluated for antibacterial and antifungal activities. Some synthesized compounds exhibited better antibacterial and antifungal efficacy than clinical drugs Fluconazole, Norfloxacin and Chloramphenicol. © 2010 Elsevier Masson SAS. All rights reserved.

Lei B.,Chongqing Medical University
Advances in Experimental Medicine and Biology | Year: 2010

Due to its high ocular transduction, low immune clearance and capability to bypass the brain blood barrier, adeno-associated virus-9 (AAV9) has been regarded as a promising vector for retinal disease gene therapy.We recently demonstrated that AAV9 efficiently transduces the retinal outer plexiform layer (OPL). The OPL consists of synapses formed between axons of the rod and cone photoreceptors (cell bodies in the outer nuclear layer, ONL) and dendrites of bipolar and horizontal cells (cell bodies in the inner nuclear layer, INL). It is not clear whether AAV9 transduces the OPL through the photoreceptors in the ONL or through bipolar and horizontal cells in the INL. To map the subcelluar pathway(s) involved in AAV9-mediated OPL transduction, we delivered subretinally AAV9.CMV.eGFP, an AAV vector carrying the enhanced green fluorescent protein gene (eGFP, 1 × 1010 viral genome particles in microliter), to young (21-day-old) and adult (2- to 3-month-old) C57BL/6 mice. Four weeks after subretinal injection, eGFP expression was examined on retinal cryosections. PSD95 (postsynaptic density protein, a marker for photoreceptor terminals), CtBP2 (C-terminal binding protein 2, a marker for the photoreceptor synaptic ribbon), PKCalpha (protein kinase Ca, a marker for rod bipolar cells), and calbindin (a marker for horizontal cells) were localized by immunofluorescence staining. In AAV9 infected retina, eGFP expression was seen in the retinal pigment epithelia, photoreceptor inner segments, ONL, OPL, Müller cells in the INL, inner plexiform layer and ganglion cell layer. Interestingly, eGFP expression co-localized with PSD95 and CtBP2, but not with PKCalpha and calbindin. Our results suggest that AAV9 transduces the photoreceptor side of the synapses in the OPL rather than the dendrites of bipolar and horizontal cells. © Springer Science+Business Media, LLC 2010.

Feng X.,University of Sichuan | Zhou Z.,University of Sichuan | Ma C.,University of Sichuan | Yin X.,University of Sichuan | And 4 more authors.
Angewandte Chemie - International Edition | Year: 2013

Newly framed: The δ,ε Cï£C bond of an interrupted cyclic 2,5-dienone induces the formation of a linear trienamine in the presence of a chiral primary amine, thus enabling the δ,ε-Cï£C bond to participate in a highly asymmetric inverse-electron-demand aza-Diels-Alder (DA) reaction with electron-deficient 1-azadienes. The DA reaction can be coupled with a Michael addition to produce a polycyclic framework with complete stereocontrol. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Yin Z.Q.,Chongqing Medical University
Advances in Experimental Medicine and Biology | Year: 2010

Müller cells can be activated and included in different functions under many kinds of pathological conditions, however, the status of Müller cells in retinitis pigmentosa are still unknown. Using immunohistochemisty, Western blots and co-culture, we found that Müller cells RCS rats, a classic model of RP, could be activated during the progression of retinal degeneration. After being activated at early stage, Müller cells began to proliferate and hypertrophy, while at later stages, they formed a local 'glial seal' in the subretinal space. As markers of Müller cells activation, the expression of GFAP and ERK increased significantly with progression of retinal degeneration. Co-cultures of normal rat Müller cells and mixed RCS rat retinal cells show that Müller cells significantly increase GFAP and ERK in response to diffusable factors from the degenerting retina, which implies that Müller cells activation is a secondary response to retinal degeneration. © Springer Science+Business Media, LLC 2010.

Ma C.,University of Sichuan | Jia Z.-J.,University of Sichuan | Liu J.-X.,University of Sichuan | Zhou Q.-Q.,University of Sichuan | And 3 more authors.
Angewandte Chemie - International Edition | Year: 2013

Ideal relay catalysis: A γ,δ-regioselective anomalous exo-Diels-Alder reaction with electron-deficient β-substituted 2,4-dienes and 2,4-dienals has been developed by using trienamine activation. The resulting multifunctional cycloadducts contain perfectly positioned functional groups, thereby facilitating a 1,5-hydride transfer from the C-H group of an aldehyde to an activated alkene under sequential catalysis of a carbene (see scheme). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recent studies on the association between CD14-159C/T polymorphism and sepsis showed inconclusive results. Accordingly, we conducted a comprehensive literature search and a meta-analysis to determine whether the CD14-159C/T polymorphism conferred susceptibility to sepsis or was associated with increased risk of death from sepsis. Data were collected from the following electronic databases: PubMed, Embase, Medline, Web of Knowledge, and HuGE Navigator, with the last report up to June 15, 2012. The odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of association. We summarized the data on the association between CD14-159C/T polymorphism and sepsis in the overall population and subgroup by ethnicity and sepsis subtype. A total of 16 studies on sepsis morbidity (1369 cases and 2382 controls) and 4 studies on sepsis mortality (731 sepsis patients) met the inclusion criteria for meta-analysis. Overall analysis showed no strong evidences of association with sepsis susceptibility under any genetic model. However, slight associations were found in Asian populations (dominant model: OR = 1.38, 95%CI = 0.96-1.98, P = 0.08) and septic shock patients (dominant model: OR = 1.72, 95%CI 1.05-2.83, P = 0.03; allelic model: OR = 1.52, 95%CI 1.09-2.12, P = 0.01) in the stratified analysis. Moreover, there was borderline association between CD14-159C/T and sepsis mortality under the dominant genetic model (OR = 1.44, 95%CI = 0.98-2.11, P = 0.06). This meta-analysis suggests that the CD14-159C/T polymorphism may not be a significant susceptibility factor in the risk of sepsis and mortality. Only weak associations were observed in Asian populations and septic shock patients. More studies based on larger sample sizes and homogeneous sepsis patients are needed to confirm these findings.

Chen S.,Zhejiang University | Yang Q.,Chongqing Medical University | Chen G.,Soochow University of China | Zhang J.H.,Loma Linda University
Translational Stroke Research | Year: 2014

Intracerebral hemorrhage (ICH) is a common and severe neurological disorder, which is associated with high rates of mortality and morbidity. Despite extensive research into the pathology of ICH, there are still no clinically approved neuroprotective treatments. Currently, increasing evidence has shown that inflammatory responses participate in the pathophysiological processes of brain injury following ICH. In this editorial, we summarized some promising advances in the field of inflammation and ICH, which contained animal and human investigations; discussed the role of neuroinflammation, systemic inflammatory responses, and some potential targets; and focused on the challenges of translation between pre-clinical and clinical studies and potential anti-inflammatory therapeutic approaches after ICH. © 2014, Springer Science+Business Media New York.

Xia L.-J.,Chongqing Medical University
Chinese Journal of Biologicals | Year: 2011

Objective: To study the preventive effect of HpaA-VacA IgY on the intragastric colonization of Helicobacter pylori and the subsequent inflammation in mice, and lay a foundation of developing IgY-related drugs for both prevention and therapy of H. pylori infection. Methods: BALB/c mice were randomly divided into positive control, negative control, infection-preventing and inflammation-preventing groups. The mice in positive control group were administered with 108 cfu/ml H. pylori liquid by intragastric infusion, while those in negative control group with Brucella broth. The mice in infection-preventing group were administered with IgY at various dosages, then with 108 cfu/ml H. pylori liquid. However, the mice in inflammation-preventing group were administered with 108 cfu/ml H. pylori liquid, then with IgY at various dosages. The colonization of H. pylori and severity of inflammatory reaction were observed by culture of intragastric H. pylori and microscopy of stained histological sections. Results: The prevention rate of H. pylori infection by HpaA-VacA IgY at a dosage of 6 mg was 88.9%. However, the HpaA-VacA IgY at a dosage of 8 mg completely protected the mice against H. pylori infection and the subsequent inflammation. Conclusion: Oral administration with HapA-VacA IgY showed both preventive and curative effects on H. pylori infection in mice, indicating that the IgY might be used for preparation of oral drug for H. pyhri infection.

Zhang X.,Chongqing Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2013

To investigate the effect of low-intensity pulsed ultrasound (LIPUS) on the extracellular matrix synthesis of human degenerative nucleus pulposus cells and explore the underlying mechanism. The nucleus pulposus cells acquired from human degenerative lumbar intervertebral discs were cultured by monolayer culture and identified. After three passages, the cells were cultured in calcium alginate beads. Experimental groups were stimulated by LIPUS (LIPUS group) for 1 week (20 min/d) or treated with LY294002 simultaneously (LY294002 group), and control group was treated in the same way without LIPUS stimulation. The concentrations of aggrecan and Col2α1 in culture supernatant were detected by ELISA. The expression levels of aggrecan and Col2α1 mRNA were dertermined by RT-PCR. The expression levels of aggrecan, Col2α1, Akt and p-Akt proteins were examined by Western blotting. The concentrations of aggrecan and Col2α1 in the LIPUS group group was significantly higher than those in the control group (P<0.05). The expressions of aggrecan and Col2α1 at both mRNA and protein levels and p-Akt protein significantly increased in the LIPUS group as compared with the control group (P<0.05), but there was no significant difference in the expression of Akt protein between the two groups(P>0.05). The levels of aggrecan and Col2α1 proteins were significantly lower in the LY294002 group than in the LIPUS group (P<0.05). The LIPUS can stimulate the extracellular matrix synthesis of degenerative human nucleus pulposus cells cultured in calcium alginate beads via activating PI3K/Akt pathway.

Cheng H.,Chongqing Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2013

glucagonoma is a rare islet alpha-cell tumor. We report a case of glucagonoma in a 55-year-old male patient with such clinical findings of necrolytic migratory erythema, diabetes mellitus, body weight loss, and anemia. CT examination found a space-occupying lesion in the pancreas, and an elevated serum glucagon level indicate the diagnosis of glucagonoma, which was confirmed postoperatively by pathological examination of the tumor tissue. A definite diagnosis of glucagonoma relies on pathological report, and so far no standard treatment strategy has been available for this tumor. Surgical resection is an effective means for treatment of glucagonoma.

Zhang S.-J.,University of Sichuan | Zhang J.,University of Sichuan | Zhou Q.-Q.,University of Sichuan | Dong L.,University of Sichuan | And 2 more authors.
Organic Letters | Year: 2013

An asymmetric exo-Diels-Alder reaction of α-methylene carbonyl compounds, generated in situ from stable methiodide salts of Mannich bases, with 2,4-dienals, has been developed through trienamine activation of a chiral secondary amine. A spectrum of spirocyclanes with high molecular complexity was efficiently constructed in moderate to excellent diastereo- and enantioselectivity. © 2013 American Chemical Society.

Nan Y.,University of Maryland University College | Nan G.,University of Maryland University College | Nan G.,Chongqing Medical University | Zhang Y.-J.,University of Maryland University College
Viruses | Year: 2014

Interferons are a group of small proteins that play key roles in host antiviral innate immunity. Their induction mainly relies on host pattern recognition receptors (PRR). Host PRR for RNA viruses include Toll-like receptors (TLR) and retinoic acid-inducible gene I (RIG-I) like receptors (RLR). Activation of both TLR and RLR pathways can eventually lead to the secretion of type I IFNs, which can modulate both innate and adaptive immune responses against viral pathogens. Because of the important roles of interferons, viruses have evolved multiple strategies to evade host TLR and RLR mediated signaling. This review focuses on the mechanisms of interferon induction and antagonism of the antiviral strategy by RNA viruses. © 2014 by the authors; licensee MDPI, Basel, Switzerland.

Zhu Q.,Chongqing Medical University
Journal of molecular neuroscience : MN | Year: 2012

DNA methylation is a key epigenetic modification of DNA that is catalyzed by DNA methyltransferase (DNMT). Increasing evidence suggests that DNA methylation in neurons regulates synaptic plasticity as well as neuronal network activity. Here, we evaluated DNA methyltransferase 1 (Dnmt1) and Dnmt3a expression in brain tissues of epileptic patients to explore their possible role in epileptogenesis. Tissue samples from temporal neocortices of 25 patients with intractable temporal lobe epilepsy (TLE) and ten histologically normal temporal lobes from control patients were used to detect Dnmt1 and Dnmt3a expression through immunohistochemistry, immunofluorescence, and Western blotting analysis. We found that both Dnmt1 and Dnmt3a expression were principally expressed in the nucleus and the cytoplasm of NeuN-positive neurons, but not in GFAP-positive astrocytes. Levels of the two DNMT proteins were significantly increased in patients with TLE. Our study suggests that DNMT1 and DNMT3a may play a role in the pathogenesis of TLE.

Li Z.H.,Chongqing Medical University
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban | Year: 2011

To study the brain protection of baicalin on rats with Alzheimer's disease (AD) and its probable mechanism of action. Thirty-six male healthy Wistar rats were randomly divided into the sham-operative group, the AD group, and the baicalin group, twelve in each. beta-amyloid protein 1-40 was injected to the bilateral hippocampus of rats in the AD group and the baicalin group to establish the AD rat model. The sham operation was performed to rats of the sham-operative group in the same way. Equal volume of 0.9% sodium chloride solution was injected to the bilateral hippocampus of rats in the sham-operative group. Baicalin was intraperitoneally injected at the daily dose of 40 mg/kg to rats in the baicalin group before and after operation, once daily for 7 successive days. Equal volume of buffer solution was intraperitoneally injected to rats in the sham-operative group and the AD group in the same procedures at the same time points. The expression of hippocampal cyclooxygenase-2 (COX-2) was determined by Western blot. The spatial learning memory capacities was observed using T-morris test. Histological changes were observed using hematoxylin-eosin (HE) staining. Results of the T-morris test showed the spontaneous alternation selective ratio decreased in the AD group (28.33% +/- 7.50%) and the baicalin group (38.33% +/- 7.50%) (both P < 0.05) when compared with the sham-operative group (61.67% +/- 7.50%). There was significant difference between the AD group and the baicalin group (P < 0.05). Results of HE staining showed degeneration and necrosis of cortical and hippocampal neurons in the AD group and the baicalin group. Changes in the AD group were more obvious. Results of Western blot showed the expression of hippocampal cyclooxygenase (COX-2) obviously increased in the AD group, while it obviously decreased in the baicalin group (P < 0.05). Baicalin could alleviate beta-amyloid protein induced brain injury, which might be associated with its inhibition on the COX-2 expression.

Chen G.-J.,Chongqing Medical University | Xiong Z.,State University of New York at Buffalo | Yan Z.,State University of New York at Buffalo
Molecular Neurodegeneration | Year: 2013

Background: Accumulation of β-amyloid (Aβ) and cholinergic deficiency are two prominent features of Alzheimer's disease (AD). To understand how Aβ-induced dysfunction of the nicotinic system may contribute to cognitive impairment in AD, we examined the effect of Aβ on nicotinic regulation of synaptic transmission and neuronal excitability in prefrontal cortex (PFC), a brain region critical for cognitive processes. Results: We found that activation of nicotinic acetylcholine receptors (nAChRs) with nicotine increased the inhibitory postsynaptic currents recorded in PFC pyramidal neurons, which was associated with the nicotine-induced increase in the excitability of PFC layer I GABAergic interneurons. Both effects of nicotine were disrupted by Aβ. However, Aβ did not impair nicotinic regulation of excitatory neurotransmission in PFC interneurons. The nicotinic effect on synaptic inhibition was also lost in transgenic mice with five familial Alzheimer's disease mutations. Inhibiting PKC attenuated nicotinic regulation of inhibitory, but not excitatory, neurotransmission. Conclusions: Our study suggests that Aβ selectively impairs nicotinic regulation of inhibitory inputs to PFC pyramidal neurons, which might be due to its interference with PKC activation. Thus, in the PFC circuits of AD, the balance between inhibition and excitation under the control of nAChRs may be disturbed by Aβ. © 2013 Chen et al.; licensee BioMed Central Ltd.

Objective: To observe the regulatory effect of amlodipine on expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in murine melanoma B16 and investigate the mechanism of amlodipine in inhibiting the metastasis of tumors. Methods: The effect of amlodipine on proliferation of B16 cells was determined by MTT method. C57BL/6 mouse model of spontaneous pulmonary metastasis of melanoma B16 was established. The model mice were randomly divided into negative control(physiological saline), positive control[cytoxan(CTX) 20 mg/kg] and amlodipine at high [10 mg/(kg·d)], moderate [3 mg/(kg·d)] and low [1 mg/(kg·d)] groups. The MMP-9 activity in tumor tissue was determined by gelatin zymography, while the expressions of MMP-9 and TIMP-1 mRNAs by RT-PCR, and expressions of MMP-9 and TIMP-1 proteins by immunohistochemical assay with SP staining. Results: Amlodipine showed time- and dose-dependent inhibitory effect on the growth of B16 cells, of which the IC 50 48 h after treatment was 11.56 μmol/L. Results Amlodipine down-regulated the MMP-9 activity as well as expressions of MMP-9 mRNA and protein in tumor tissue, while up-regulated the expressions of TIMP-1 mRNA and protein. Conclusion: Amlodipine inhibited the metastasis of tumor by regulating the expressions of MMP-9 and TIMP-1 genes.

Dai Z.Y.,Chongqing Medical University
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology | Year: 2011

To investigate the relationship of NOR-1 with the inhibition of inflammatory reaction in mice Kupffer cells (KCs) induced by lipopolysaccharide (LPS) via liver X receptor alpha (LXR alpha). KCs from male KM mice were isolated by density gradient centrifugation, incubated and then randomly assigned to three groups: control group, LPS treated group and LPS+T0901317 treated group. The mRNA and protein expressions of LXR alpha and NOR-1 in each group were determined by RT-PCR, immunofluorescent assay and western blot, respectively. The densities of TNF alpha and IL-10 in supernatants were evaluated by enzyme linked immunosorbent assay (ELISA). The mRNA and protein expression levels of LXR alpha in LPS + T0901317 group were the highest as compared to the other two groups (0.748+/-0.072 and 1.217+/-0.133 respectively), The mRNA and protein expression levels of NOR-1 in LPS+ T0901317 group were the highest as compared to the other two groups (2.726+/-0.065 and 0.842+/-0.058 respectively). The densities of supernatant TNF alpha in LPS group and IL-10 in LPS+T0901317 group were the highest [(450.89+/-78.52) ng/L and (537.41+/-36.41) ng/L respectively]. Promoting the expression of LXR alpha in KCs can elevate the NOR-1 expression and then inhibit inflammatory reaction.

Yu M.,Chongqing Medical University
Zhen ci yan jiu = Acupuncture research / [Zhongguo yi xue ke xue yuan Yi xue qing bao yan jiu suo bian ji] | Year: 2011

To observe the effect of different intensities of electroacupuncture (EA) on adipose tissue inflammatory cytokines in rats with simple obesity so as to investigate its mechanism underlying body weight reduction. Forty SD male rats were randomly divided into normal, model, strong EA and weak EA groups (n = 10/group). Obesity model was established by feeding the rats with high fat diet. EA (20 Hz, strong EA: 5 V, weak EA: 2. 5 V) was applied to "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) for 15 min, once everyday and for 14 days. Body weight and Lee's index (= body weight(1/3) x 10(3) / body length) were detected. The fasting blood glucose was detected by hexokinase method, serum triglyceride (TG) was detected by glycerol-phosphoric acid oxidase peroxydase (GPO-POD)method, total cholesterol (TC) was detected by cholesterol oxidase method, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-O) were measured by using one-step method, respectively. The expression of monocyte chemoattractant protein-1 (MOP-1) mRNA and tumor necrosis factor (TNF)-alpha mRNA in the epididymis adipose tissue was detected by reverse transcription-polymerase chain reaction (RT-POR). In comparison with the normal group, the body weight, Lee's index, blood lipid (TG, TC, LDL-C), fasting blood glucose levels, and expression of MOP-1 mRNA and TNF-alpha mRNA were significantly higher in the model group (P < 0.01), and HDL-C was significantly lower (P < 0.01). After EA,compared with the model group, the body weight, Lee's index, TG, TC, LDL-C, fasting blood glucose levels, and expression of MCP-1 mRNA and TNF-a mRNA in both strong and weak EA groups were significantly decreased (P < 0.01, P < 0.05), and HDL-C was significantly increased (P < 0.01, P < 0.05). The effects of strong EA group were obviously superior to those of weak EA group (P < 0.05, P < 0.01). No statistical significance was observed between the two EA groups in fasting blood glucose levels (P > 0.05). EA of "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) has a beneficial weight-reduction effect on rats with simple obesity, and moreover, the effect of strong EA stimulation is evidently superior to weak EA stimulation.

Gao-Yu C.,Chongqing Medical University
Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, Inc | Year: 2011

This study aimed to evaluate the effect of hyperbaric oxygen preconditioning (HBO2P) on ischemic metabolites and the glutamate level after permanent middle cerebral artery occlusion (MCAO). HBO2P was administered: five treatments, one treatment per day. The permanent rabbit MCAO models were induced by a modified transorbital approach. The microdialysis procedures were performanced in the right peri-infarct area and contralateral area. MCAO decreased glucose levels while increasing lactate, pyruvate and lactate/pyruvate ratios. Early increase of glycerol and glutamate were also shown. HBO2P stabilized the glucose level and decreased the lactate/pyruvate ratios and glycerol in the peri-infarct area. In addition, it inhibited the increase of the glutamate level. Our study demonstrated that MCAO led to the imbalance of brain energy metabolites and excitatory amino acids. The modulation of energy metabolism and glutamate may be one of the factors contributing to the neuroprotective property of HBO2P.

Liu Y.,Xiamen University | Wang D.,Molecular Biology Research Center | Li F.,Chongqing Medical University | Shi G.,Xiamen University
Immunology and Cell Biology | Year: 2015

Gαq, the α-subunit of Gq protein, is ubiquitously expressed in mammalian cells. It initially attracted attention for its physiological significance in cardiovascular system. In recent years, studies have also indicated the important roles of Gαq in regulating immunity, supplying us a new insight into the mechanism of immune regulation. T helper type 17 (Th17) cells are potent inducers of tissue inflammation. Many studies have shown that Th17 cells are major effector cells in the pathogenesis of many experimental autoimmune diseases and human inflammatory conditions such as rheumatoid arthritis (RA). One of our previous studies has shown that Gαq negatively controls the disease activity of RA. However, how Gαq controls the pathogenesis of autoimmune disease is not clear. Whether this effect is via the regulation of Th17 differentiation is still not known. We aimed to find out the role of Gαq in control of Th17 differentiation. We investigated the relationship between Gαq and Th17 in RA patients. We then investigated the mechanism of how Gαq regulated Th17 differentiation by using Gnaq-/- mice. We observed that the expression of Gαq was negatively associated with interleukin-17A expression in RA patients, indicating that Gαq negatively controlled the differentiation of Th17 cells. By using Gnaq-/- mice, we demonstrated that Gαq inhibited the differentiation of Th17 cell via regulating the activity of extracellular signal-regulated kinase-1/2 to control the expression of STAT3 (signal transducer and activator of transcription 3) and RORα (RAR-related orphan receptor-α). These data suggest the possibility of targeting Gαq to develop a novel therapeutic regimen for autoimmune disease.

Huang Q.,Chongqing Medical University
The journal of headache and pain | Year: 2013

Many studies have reported that hypertension is common in chronic daily headache (CDH) and its subtype chronic migraine (CM), but the reason is still poorly understood. Our clinical literature review suggested that analgesic overuse may be associated with elevated blood pressure (BP), so we performed the present study to investigate the frequency of elevated BP and its link with analgesic overuse in CDH and its subtypes. A cross-sectional study was conducted in neurology outpatients with a diagnosis of CDH according to International Headache Society criteria. CDH patients were classified into CM and non-CM groups, and subclassified with or without analgesic overuse. Elevated BP was present in 27.96% of CDH patients. Compared with non-CM patients, patients with CM had a longer duration of headache and more severe pain intensity, and a family history of headache and analgesic overuse were also more common, but the elevated BP frequency was not different between the two groups. Almost one-third of the patients had analgesic overuse; 96.8% of which comprised acetaminophen-containing agents. Those with analgesic overuse had a higher frequency of headache than those without analgesic overuse in both the CM and non-CM groups. Although the CM patients had a longer duration of headache, more severe intensity, the frequency of elevated BP wasn't higher than non-CM group. Analgesic overuses maybe the reason of higher frequency of elevated BP in CDH and its subtypes. This may have predictive value for clinicians to improve CDH management.

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

To construct the prokaryotic expression plasmid pEGX-6P-1-SAK-HC, express it in E.coli, and identify its biological activity. The fusion gene (SAK-HC) was obtained by overlap-extension PCR and then inserted into prokaryotic soluble pEGX-6P-1 vector with GST tag to construct expression plasmid (pEGX-6P-1-SAK-HC). GST-SAK-HC was expressed by E.coli B834 (DE3) under the induction of IPTG and purified by Glutathion-Sepharose 4B (GST) affinity chromatography and negative-ion exchange column (DEAE) chromatography. PreScission protease was used to remove the GST tag. The purity of the fusion protein was analyzed by SDS-PAGE and the fibrinolytic activity of SAK-HC in vitro was characterized by soluble fibrin plate method. PCR, sequencing and restriction enzyme digestion analysis demonstrated that the recombinant plasmid was constructed successfully. The fusion protein was expressed in E.coli B834 (DE3), M(r); being 36 000 as shown by SDS-PAGE. After purified by GST affinity and DEAE chromatography, SAK-HC fusion protein of high purity was obtained from the cell supernantants. In vitro experiments showed that the fibrinolytic activity of the recombinant SAK-HC was about 9.4×10();4 IU/mg. The SAK-HC fusion protein we obtained was successfully expressed in E.coli and exhibited a fibrinolytic activity as high as the urokinase standard, which offers a base for the identification of immunogenicity of the fusion protein.

Jin L.,Chongqing Medical University
Wei sheng wu xue bao = Acta microbiologica Sinica | Year: 2012

Riboflavin, called generally vitamin B12, is the precursor of cofactor flavin adenine dinucleotide (FAD) and flavin mononucleotide, which plays crucial roles in the biosynthesis of organisms. Bacteria need to synthesize riboflavin to maintain their survival and proliferation if they cannot obtain flavin from the surroundings. 3,4-Dihydroxy-2-butanone4-phosphate synthase (DHBPs) is one of the key enzymes in biosynthesis of riboflavin. In the presence of Mg2+, DHBPs can degrade ribulose-5-phosphate (Ru5P) into formate and 3,4-dihydroxy-2-butanone-4-phosphate (DHBP). Potentially, these enzymes related to biosynthesis and metabolism of riboflavin, including DHBPs, may serve as the target for new antibacterial drug. In order to determine the three-dimensional structure and screen small molecule of inhibitor of DHBPs, we expressed and purified DHBPs from Streptococcus pneumonia (S. pn), and characterized the activity of this enzyme. DHBPs gene was amplified by PCR, and over-expression plasmid pW28-DHBPs was constructed. pW28-DHBPs was transformed into Escherichia coli BL21 (DE3) to express DHBPs; the recombinant protein was purified by nickel column and ion-exchange column. The enzymatic activity was tested using spectroscopy. The plasmid of pW28-DHBPs was verified by restrictive enzyme digestion and sequencing. Soluble DHBPs was expressed in E. coli BL21, and purified with 95% purity. The result of size exclusion chromatography indicates that DHBPs was dimer in solution. Additionally, the recombinant protein has activity to hydrolyze Ru5P into formate and DHBP in the conditions of pH 7.5 and 25 degrees C and in the presence of Mg2+. DHBPs could be highly expressed in soluble form in E. coli BL21 strain, and the recombinant protein has activity to hydrolyze Ru5P.

Ma C.,Chongqing Medical University
Zhonghua nan ke xue = National journal of andrology | Year: 2011

To observe the effects of flutamide (Flu) on the development of testicular germocytes in SD rats, and to establish a rat model for further researches on the maldevelopment of cryptorchidism gonocytes (Go). Pregnant SD rats were subcutaneously injected with Flu from gestational day (GD) 12 to 21 to establish a model of cryptorchidism. The testes of the newborns were harvested on postnatal day (PD) 1, 10, 20 and 80 for observation of their morphological and histological changes by HE staining and detection of the expression of neural cell adhesion molecules (NCAM) by immunohistochemistry and RT-PCR. Flu induced 43.9% (29/66) of cryptorchidism in the exposed rats. Significant differences were found in the testicular weight and organ coefficient between the Flu and the control groups on PD 20 and 80. Gos remained in the center of seminiferous tubules of the Flu-induced testis on PD 10, and in the center of seminiferous tubules in the cryptorchids' testicular tissues on PD 20 and 80. Immunohistochemistry showed the expression of NCAM on the membrane of the remaining Gos, and RT-PCR revealed significantly up-regulated expression of NCAM mRNA in the Flu-induced testes on PD 10 and 20 as compared with the controls (P < 0.05). A rat model of Flu-induced cryptorchidism with remaining Gos was successfully established, which could be used to study the mechanism and management of the maldevelopment of cryptorchidism gonocytes.

Liao Y.,Huazhong University of Science and Technology | Liu P.,Huazhong University of Science and Technology | Guo F.,Huazhong University of Science and Technology | Zhang Z.-Y.,University of Tubingen | Zhang Z.,Chongqing Medical University
PLoS ONE | Year: 2013

Besides secondary injury at the lesional site, Traumatic brain injury (TBI) can cause a systemic inflammatory response, which may cause damage to initially unaffected organs and potentially further exacerbate the original injury. Here we investigated plasma levels of important inflammatory mediators, oxidative activity of circulating leukocytes, particularly focusing on neutrophils, from TBI subjects and control subjects with general trauma from 6 hours to 2 weeks following injury, comparing with values from uninjured subjects. We observed increased plasma level of inflammatory cytokines/molecules TNF-α, IL-6 and CRP, dramatically increased circulating leukocyte counts and elevated expression of TNF-α and iNOS in circulating leukocytes from TBI patients, which suggests a systemic inflammatory response following TBI. Our data further showed increased free radical production in leukocyte homogenates and elevated expression of key oxidative enzymes iNOS, COX-2 and NADPH oxidase (gp91phox) in circulating leukocytes, indicating an intense induction of oxidative burst following TBI, which is significantly greater than that in control subjects with general trauma. Furthermore, flow cytometry assay proved neutrophils as the largest population in circulation after TBI and showed significantly up-regulated oxidative activity and suppressed phagocytosis rate for circulating neutrophils following brain trauma. It suggests that the highly activated neutrophils might play an important role in the secondary damage, even outside the injured brain. Taken together, the potent systemic inflammatory response induced by TBI, especially the intensively increase oxidative activity of circulating leukocytes, mainly neutrophils, may lead to a systemic damage, dysfunction/damage of bystander tissues/organs and even further exacerbate secondary local damage. Controlling these pathophysiological processes may be a promising therapeutic strategy and will protect unaffected organs and the injured brain from the secondary damage. © 2013 Liao et al.

Chen Y.,Chongqing Medical University | Chen Y.,Stem Cell Institute Leuven | Verfaillie C.M.,Stem Cell Institute Leuven
Liver International | Year: 2014

MicroRNAs are a class of small non-coding RNAs involved in the transcriptional and post-transcriptional regulation of gene expression. The function of miRNAs in liver disease including hepatocellular carcinoma (HCC), hepatitis, and alcoholic liver disease, have been widely studied and extensively reviewed. Increasing evidence demonstrates that miRNAs also play a critical role in normal liver development and in the fine-tuning of fundamental biological liver processes. In this review, we highlight the most recent findings on the role of miRNAs in liver specification and differentiation, liver cell development, as well as in the many metabolic functions of the liver, including glucose, lipid, iron and drug metabolism. These findings demonstrate an important role of miRNAs in normal liver development and function. Further researches will be needed to fully understand how miRNAs regulate liver generation and metabolic function, which should then lead to greater insights in liver biology and perhaps open up the possibility to correct errors that cause liver diseases or metabolic disorders. © 2014 John Wiley and Sons A/S.

Liu X.,Chongqing Medical University
Wei sheng wu xue bao = Acta microbiologica Sinica | Year: 2012

We used a minicircle DNA vector system to express small interfering RNA (siRNA) and studied the inhibition of hepatitis B virus (HBV) replication and gene expression in vitro. siRNA targeting HBV S gene (siHBS) was designed , synthesized and cloned into a minicircle DNA vector pMC. BESPX-MCS2. After sequencing, we transformed the recombinant pMC-H1-siHBS-U6 into E. coli ZYCY10P3S2T, and induced the degradation of its bacterial backbone by adding L-arabinose into the bacterial growth medium. As expected, a minicircle RNA interference (RNAi) vector pmc-H1-siHBS-U6 was generated only consisting of gene expression cassette. Then pmc-H1-siHBS-U6 was co-transfected into Huh-7 cells with HBV expression vector pHBV1.3. ELISA and Real-time PCR were performed to evaluate the inhibition effect of the secretion of HBsAg and HBeAg and the levels of HBV DNA and mRNA in Huh-7 cells. We Successfully established the minicircle-based RNAi vector pmc-H1-siHBS-U6, which can significantly inhibit the secretion of HBsAg and HBeAg in Huh-7 cells for two to three weeks. Real-time PCR results show that HBV DNA and mRNA levels were also down-regulated about 71% and 80%. The minicircle DNA-based RNAi vector pmc-H1-siHBS-U6 can suppress HBV replication and gene expression specifically, efficiently and steadily. Thus, this study provided us a new siRNA delivery system and a new gene therapy strategy of HBV infection.

Duan H.,Chongqing Medical University
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2010

To study the effect of the Zichong Granules (ZG) on follicular development by rectal administration. Underage rats and ovariectomized mice were administered with ZG by clyster perfusion. Diethylstilbestrol and Nvjindan (NJD) were taken as control. Ovarian follicle, corpus luteum of rats were counted. Uterus index and histomorphology of uterus of rats and mice were observed. In addition, E2 in blood of mice were determined by enzyme immunoassay (EIA). The effects of ZG, Diethylstilbestrol and NJD were similar. They all increased ovarian preantral follicles and total follicles of the rats (P < 0.01 or P < 0.05), uterus index and the thickness of endometrium of the rats (P < 0.05), and increased uterus index (P < 0.01),the thickness of endometrium (P < 0.05) and E2 level in blood (P < 0.05) of the mice. ZG administered by clyster perfusion can improve follicular development of underage rats, increase E2 level of ovariectomized mice, and present the estrogen-like effect. The effect of ZG for improving follicular development may be related to improving the level of E2. Rectal administration may be one of the effective ways to stimulate the follicular development.

Guo L.,Chongqing Medical University
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2011

To investigate the surgical technique and short-term effectiveness of anterior cruciate ligament (ACL) reconstruction with LARS artificial ligament. Between November 2008 and April 2010, eighty patients with ACL injury were treated with LARS artificial ligament under arthroscope and successfully followed up. There were 51 males and 29 females, aged from 17 to 43 years with an average of 29.2 years. The injuries were caused by sport in 63 cases, traffic accident in 14 cases, and bruise in 3 cases. There were 43 left knees and 37 right knees. The disease duration ranged from 10 days to 11 months. The anterior drawer test, Lachman test, and pivot shift test for all cases were rated as positive. The preoperative Lysholm score was 55.4 +/- 5.7, Irgang score was 48.3 +/- 6.2, and Larson score was 54.8 +/- 7.4; and the International Knee Documentation Committee (IKDC) score was lower than normal level in all cases. Oblique coronal MRI showed ACL injury in all cases. Residual ACL and synovium were preserved during surgery. All incisions healed by first intention without complication of infection or deep venous thrombosis. All patients were followed up 7 to 24 months with an average of 16.8 months. There were 3 cases of screws exposure toward femoral cortical bone, 2 cases of loosening tibial screw, and 1 case of knee extension limitation, and they were cured after symptomatic treatment. No LARS artificial ligament rupture and joint fibrosis occurred during follow-up. At last follow-up, the results of anterior drawer test, Lachman test, and pivot shift test were positive in 2, 3, and 3 patients, respectively. There were significant differences in Lysholm, Irgang, and Larson scores of affected knees between preoperation and 6 weeks postoperatively, last follow-up, respectively (P < 0.05). The normal rate of IKDC score were 43.75% (35/80) and 97.50% (78/80) at 6 weeks postoperatively and last follow-up, respectively. The viscoelastic properties of LARS artificial ligament is different from that of biological materials. The graft should be fixed at a relatively extension position to avoid knee extension limitation and slight loosening of graft tension is permitted at flexion position. Good clinical result could be achieved if the technique is well applied.

Ye Y.J.,Chongqing Medical University
Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases | Year: 2010

To investigate the weight reduction of hydatid cyst and the changes of cytokine secretion in mice immunized by leaf protein extracted from Echinococcus granulosus (Eg) Eg95-EgA31 transgenic alfalfa and challenged by Eg protoscoleces. Leaf protein was extracted from E. granulosus Eg95-EgA31 transgenic alfalfa by heat coagulation method. Meanwhile, leaf protein extracted from transgenic alfalfa containing pBI121 and normal alfalfa served as control. 32 female BALB/c mice were randomly divided into 4 groups. Groups A and B were immunized intragastrically (100 p1) and intranasally (10 microl) respectively by leaf protein containing Eg95-EgA31 fusion antigen, group C was vaccinated intranasally by 10 microl. leaf protein with pBI121, group D was given intragastrically 100 microl normal leaf protein. All mice were immunized once per 3 days for 2 months. Mice in all groups were challenged with 50 Eg protoscoleces on the 8th week after vaccination and sacrificed on the 24th week after infection. The weight of hydatid cysts was measured and weight-reduction rate was calculated. Spleens were collected to prepare splenocytes which were cultured under stimulation with EgAg, concanavalin A (ConA) or lipopolysaccharide (LPS). The supernatant was collected to measure Objective To investigate the weight reduction of hydatid cyst and the changes of cytokine secretion in mice immunized by leaf protein extracted from Echinococcus granulosus (Eg) Eg95-EgA31 transgenic alfalfa and challenged by Eg protoscoleces. Leaf protein was extracted from E. granulosus Eg95-EgA31 transgenic alfalfa by heat coagulation method. Meanwhile, leaf protein extracted from transgenic alfalfa containing pBI121 and normal alfalfa served as control. 32 female BALB/c mice were randomly divided into 4 groups. Groups A and B were immunized intragastrically (100 microl) and intranasally (10 microl) respectively by leaf protein containing Eg95-EgA31 fusion antigen, group C was vaccinated intranasally by 10 microl. leaf protein with pBI121, group D was given intragastrically 100 microl normal leaf protein. All mice were immunized once per 3 days for 2 months. Mice in all groups were challenged with 50 Eg protoscoleces on the 8th week after vaccination and sacrificed on the 24th week after infection. The weight of hydatid cysts was measured and weight-reduction rate was calculated. Spleens were collected to prepare splenocytes which were cultured under stimulation with EgAg, concanavalin A (ConA) or lipopolysaccharide (LPS). The supernatant was collected to measure the level of IL-12, IL-10, IFN-gamma and TNF-alpha by ELISA. The average weight of hydatid cysts in groups A, B, C, and D was (28.0 +/- 36.0), (41.0 +/- 33.0), (72.0 +/- 36.0) and (78.0 +/- 57.0) mg, respectively, the cyst weight of group A was lower than that of group D (P < 0.05), decreased by 64.1%. The levels of IFN-gamma, IL-12 and TNF-alpha in group A [(925.0 +/- 88.6), (22.5 +/- 2.7) and (82.5 +/- 11.7) pg/ml] were higher than those of group D (P < 0.01), while the IL-10 level in group A [(125.0 +/- 26.7) pg/ml] was significantly lower than that of group D (P < 0.01). The level of IFN-gamma [(750.0 +/- 100.0) pg/ml] and TNF-alpha [(80.0 +/- 13.1) pg/ml] in group B was significantly higher than those of group D (P < 0.01); but there was no significant difference in the level of IL-12 and IL-10 between the two groups (P > 0.05). No considerable difference in the cytokines was found between group C and group D (P > 0.05). The levels of the 4 cytokines in groups stimulated by EgAg, ConA or LPS were higher than those without stimulation (P < 0.05 or < 0.01), and those in groups stimulated by ConA or LPS were higher than groups stimulated by EgAg (P < 0.05 or < 0.01). Th1 response may be induced in mice by immunization with the leaf protein extracted from Echinococcus granulosus Eg95-EgA31 transgenic alfalfa to resist the challenge of Eg protoscoleces.

Liu C.,Chongqing Medical University
Journal of experimental & clinical cancer research : CR | Year: 2010

BACKGROUND AND AIM: in recent years, Livin, a new member of IAPs family, is found to be a key molecule in cancers. Researchers consider Livin may become a new target for tumor therapy; however, the role of it in bladder cancer is still unclear. The purpose of this article is to investigate Antisense Oligonucleotide (ASODN) of Livin on treating bladder cancer cell and underlying mechanisms. METHODS: Phosphorathioate modifying was used to synthesize antisense oligonucleotides targeting Livin, followed by transfection into human bladder cancer cell 5637. After transfection, Livin mRNA and protein level, cell proliferation and apoptosis changes, caspase3 level and its effect on human bladder cancer transplantable tumor in nude mice were measured. RESULT: results showed Livin ASODN effectively inhibited Livin expression and tumor cell proliferation, and these effects probably through enhanced caspase3 activity and apoptosis of tumor cells. In nude mice transplantable tumor model, Livin expressions were inhibited meanwhile caspase3 expression was increased. Tumor growth slowed down and apoptosis was enhanced. CONCLUSION: Our data suggest that Livin plays an important role in inhibiting apoptosis of bladder cancer cells. Livin ASODN may promote cell apoptosis, inhibit bladder cancer growth, and become one of the methods of gene therapy for bladder cancer.

Lu J.-Y.,General Hospital of Beijing Military Region | Sheng J.-Q.,Chongqing Medical University
World Journal of Gastroenterology | Year: 2015

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is an autosomal dominant genetic condition that has a high risk of colon cancer as well as other cancers due to inherited mutations in mismatch repair (MMR) genes. During the last decades, there have been great advances in research on Chinese Lynch syndrome. This review mainly focuses on the genetic basis, clinicopathologic features, diagnosis, intervention, chemoprevention, and surveillance of Lynch syndrome in China. In addition to frequently altered MMR genes, such as MLH1 , MSH2 , MSH6 , and MLH3 , other MMR-associated genes, such as those encoding human exonuclease 1, transforming growth factor β receptor 2, and alanine aminopeptidase, metastasisassociated protein 2, adenomatosis polyposis coli down-regulated 1, and hepatic and glial cell adhesion molecule have also been implicated in Chinese Lynch syndrome. Most Chinese researchers focused on the clinicopathologic features of Lynch syndrome, and it is noticeable that the most frequent extracolonic tumor in northeast China is lung cancer, which is different from other areas in China. The Chinese diagnostic criteria for Lynch syndrome have been established to identify gene mutation or methylation. With regard to chemoprevention, celecoxib may be effective to prevent polyps relapse in Lynch syndrome carriers. Additionally, a colonoscopy-based surveillance strategy for the prevention and early detection of neoplasms in Lynchsyndrome carriers has been proposed. © 2015 Baishideng Publishing Group Inc. All rights reserved.

Zhang Y.-Y.,Southwest University | Mi J.-L.,Peoples Hospital of Suining | Zhou C.-H.,Southwest University | Zhou X.-D.,Chongqing Medical University
European Journal of Medicinal Chemistry | Year: 2011

A series of novel fluconazoliums were synthesized and their bioactive evaluation as potential antibacterial and antifungal agents were described. Some target compounds displayed good and broad-spectrum antimicrobial activities with low MIC values ranging from 0.25 to 64 μg/mL against all the tested strains, including three Gram-positive bacteria (Staphylococcus aureus, MRSA and Bacillus subtilis), three Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa and Bacillus proteus) as well as two fungi (Candida albicans and Aspergillus fumigatus). Among all tested title compounds, the octyl, dichlorobenzyl, naphthyl and naphthalimino derivatives gave comparable or even better antibacterial and antifungal efficiency in comparison with the reference drugs Fluconazole, Chloromycin and Norfloxacin. © 2011 Elsevier Masson SAS. All rights reserved.

Chen A.,Rothman Institute | Fei J.,Chongqing Medical University | Deirmegian C.,Rothman Institute
The journal of knee surgery | Year: 2014

The diagnosis of periprosthetic joint infections (PJIs) has traditionally been performed by obtaining a history and physical exam, measuring serology, and performing microbiology analysis of synovial fluid and tissue samples. The measurement of serum biomarkers, such as the erythrocyte sedimentation rate and the C-reactive protein (CRP), is routinely used to diagnose PJI. However, these markers are elevated in all inflammatory conditions, necessitating the need for more specific biomarkers to diagnose PJI. Serum biomarkers such as procalcitonin, interleukin (IL)-6, tumor necrosis factor (TNF)-α, short-chain exocellular lipoteichoic acid, soluble intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 may be more specific to PJI. Synovial fluid biomarkers elevated in PJI include cytokines such as IL-1β, IL-6, IL-8, IL-17, TNF-α, interferon-δ, and vascular endothelial growth factor. More specific synovial fluid biomarkers include synovial CRP, α-defensin, human β-defensin-2 (HBD-2) and HBD-3, leukocyte esterase, and cathelicidin LL-37. These biomarkers are the future for sensitive and specific diagnosis of PJI. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Han T.,Shanghai University | Han P.,U.S. Center for Disease Control and Prevention | Peng W.,Chongqing Medical University | Wang X.-R.,Shandong University
Pharmaceutical Biology | Year: 2013

Context: Depression is one of the most common psychiatric diseases. Acorus tatarinowii Schott (Araceae) has shown many bioactivities in treatment of senile dementia and epilepsy. However, there is no report on antidepressant-like effects of the essential oil (EO) and its major components on animals under standardized experimental procedures. Objective: This study was designed to investigate the antidepressant properties of EO and asarones from the rhizomes of A. tatarinowii. Materials and methods: Gas chromatography-mass spectrometry (GC/MS) was used to determine the composition of EO. The forced swimming test (FST), tail suspension test (TST) and open-field test (OFT) were used to evaluate the antidepressant-like effects of EO and asarones. EO [30, 60, 120 or 240 mg/kg, per os (p.o.)], asarones (α-asarone and β-asarone) [5, 10 and 20mg/kg, intraperitoneal (i.p.)] and imipramine (15mg/kg, i.p.) were administered at 1h, 30min and 30min before the test, respectively. Results: From the results of GC/MS, it was found that the main components of the EO were α-asarone (9.18%) and β-asarone (68.9%). From the results of FST and TST, the immobility time can be reduced to 166±17s (p<0.01) and 146±15s (p<0.05) by EO at the dose of 120mg/kg. Moreover, significant antidepressant-like effects were shown by α-asarone with the immobility time of 178±15s (p<0.05) and 159±17s (p<0.01) in FST, or 147±12 (p<0.05) and 134±12s (p<0.01) in TST at the dose of 10 and 20mg/kg. β-Asarone also displayed antidepressant-like effects with an immobility time of 179±18s (p<0.05) in FST or 142±14 (p<0.05) in TST at 20mg/kg. However, no change in ambulation was observed in the OFT. Conclusion: The results obtained indicate that the EO and asarones from the rhizomes of A. tatarinowii can be considered as a new therapeutic agent for curing depression. © 2013 Informa Healthcare USA, Inc.

Hou C.,Chongqing Medical University
Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi | Year: 2013

This investigation was aimed to explore whether over-expression of 27heme oxygenase-1 (HO-1) could protect bone marrow mesenchymal stem cells(BMSCs)against injury induced by high-concentration glucose. We cultured BMSCs in high-concentration glucose medium, and up-regulated or inhibited HO-1 expression in BMSCs through its agonist or inhibitor. We detected the ability of BMSCs proliferation and secretion respectively by MTT and enzyme-linked immunosorbnent assay (ELISA). Then we detected the effect of BMSCs conditions medium on proliferation and migration of human umbilical vein endothelial cells (HUVECs) through scratch experiments and transwell assay. It was found that HO-1 over-expression could not only promote BMSCs proliferation, but also promote secretion of vascular endothelial growth factor (VEGF), and could further accelerate the proliferation and migration of HUVECs. It could be well concluded that HO-1-over-expressing BMSCs can not only inhibit damage induced by high-concentration glucose, but can promote the proliferation and migration of vascular endothelial cells through paracrine as well. The result indicated that HO-1-over-expressing BMSCs played an important role in the treatment of diabetic vascular complication.

Shi C.,Chongqing Medical University
Science Translational Medicine | Year: 2012

A recent report from Urano et al. described the development of near-infrared (NIR) probes for cancer detection using chemical bioconjugation of targeting agents. Here, I highlight an alternative strategy to develop cancerselective NIR imaging and theranostic agents without chemical conjugation.

Shi Y.,Chongqing Medical University
Zhonghua fu chan ke za zhi | Year: 2010

To investigate the influence of intrahepatic cholestasis of pregnancy (ICP) on the pulmonary morphologic changes of fetal rats. Twenty pregnant SD rats at 15 days of gestations were randomly divided into ICP and control group. Rats in the ICP group were subcutaneously injected with 17-alpha-ethinylestradiol and progesterone for 5 consecutive days to establish the rat ICP model, and those of the control group received subcutaneous injection of sirasimeyu also for 5 days. The levels of serum alanine aminotransferases (ALT), aspartate transamlnase (AST), and total bile salt (TBA) were measured before and after the treatment, respectively. Maternal rats were sacrificed on 21 days of gestations and hysterotomies were performed immediately. Histopathologic changes of maternal rats' livers and fetal lungs were observed under light and electron microscopes. (1) The maternal serum levels of ALT, AST, and TBA showed no significant difference between the ICP and control group [ALT: (55+/-15) vs (49+/-12) U/L; AST: (146+/-16) vs (145+/-20) U/L; TBA: (13+/-4) vs (14+/-4) micromol/L, P>0.05, respectively] before the ICP models were established, but higher levels were shown in the ICP group after [ALT: (94+/-12) vs (59+/-17) U/L; AST: (245+/-26) vs (163+/-27) U/L; TBA: (44+/-16) vs (17+/-3) micromol/L, P<0.05, respectively]. (2) The livers of maternal rats' in the ICP group were gloomy with blurred margins, however those of the control group were normal. Microscopic observed swollen and degenerated hepatocytes with narrowed hepatic sinusoid, dilated bile duct and necrosis of hepatocytes occasionally in the ICP group, while the morphology of hepatocytes and structures of lobuli hepatis in the control group were normal. (3) The fetal pulmonary tissues in the ICP group were dark, and normal in the control group. Histopathologic examination showed matured fetal pulmonary tissues with dilated and congested interstitial lung capillaries, thickened alveolar septum, mild focal inflammatory exudation and focal hemorrhage in alveolus. Furthermore, reduced microvilli, mitochondrion vacuolization, cytoplasm disintegration and increased lamellar body evacuation were observed in type II pneumonocytes in ICP group under light and electron microscopes. While fetal pulmonary tissues of the control group did not show any significant lesions. Rat model of ICP can be established with the combination of estrogen and progestin. Hyperbileacidemia in ICP rat may lead to pathological changes in fetal pulmonary tissues.

Lei B.,Chongqing Medical University | Lei B.,University of Missouri
PLoS ONE | Year: 2012

Purpose: The rodent retina does not exhibit a positive OFF-response in the electroretinogram (ERG), which makes it difficult to evaluate its OFF-pathway functions in vivo. We studied the rod-driven OFF pathway responses by using a dark-adapted 10-Hz flicker ERG procedure in mouse. Materials and Methods: Conventional ERGs and 10-Hz dark-adapted flicker ERGs were obtained in wild-type mice (C57BL/6), in mice with pure rod (cpfl1) or pure cone (rho-/-) function, and in nob1 mice which have a selective ON-pathway defect. To isolate the response from ON or OFF pathway, glutamate analogs 2-amino-4-phosphobutyric acid (APB, an ON pathway blocker) and cis-2, 3-piperidine-dicarboxylic acid (PDA, an OFF pathway blocker), were injected intravitreally. Results: The amplitude-intensity profile of the dark-adapted 10-Hz flicker ERG in the wild-type mice exhibits two peaks at middle and high light intensities. The two peaks represent rod- and cone-driven responses respectively. In APB-treated C57BL/6 mice and in nob1 mice, the dark-adapted ERG b-waves were absent. However, both rod- and cone-driven OFF pathway responses were evident with flicker ERG recording. At middle light intensities that activate only rod system, the flicker ERG responses in saline-injected nob1 mice were similar to those in APB-injected cpfl1 mice and wild-type mice. These responses are sensitive to PDA. The amplitudes of these rod-driven OFF pathway responses were approximately 20% of the total rod-driven flicker ERG responses. Conclusion: We demonstrate that the rod-OFF bipolar cell pathway is functional in the outer retina. The dark-adapted flicker ERG is practical for the evaluation of rod- and cone-driven responses, and the residual OFF pathway signals in subjects with ON pathway defects. © 2012 Bo Lei.

Wang Y.,Chongqing Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To test the effect of recombinant interleukin-4 (IL-4) and recombinant osteoprotegerin (OPG) in suppressing bone resorption induced by polyethylene wear particles.. A cranial bone allograft was introduced into the air pouches induced on the back of BALB/c mice, followed by injection of 1 ml suspension of polyethylene particles into the pouches. The mouse models were then divided into 3 groups to receive injections of saline (control), IL-4 alone, or IL-4 and OPG into the pouches. The tissues were harvested 21 days after bone implantation for molecular and histological analyses. Polyethylene wear particles-stimulated inflammatory responses (increased cellular infiltration and IL-1 and TNF production) were markedly reduced by IL-4 treatment either alone or combined with OPG (P<0.05). Polyethylene particles significantly increased tartrate-resistant acid phosphatase (TRAP) staining and bone absorption of the implanted bone graft, and IL-4 treatment, either alone or combined with OPG, obviously reduced the osteolysis induced by polyethylene particles (P<0.05). IL-4 offers protection against polyethylene wear debris-induced inflammation and bone resorption in this mouse model. IL-4 combined with OPG can be a feasible and effective therapeutic approach to the treatment and prevention of polyethylene wear debris-associated osteolysis and aseptic loosening of the prosthetic components.

Zhang C.,Umea University | Zhang C.,National University of Singapore | Liu Y.,Chongqing Medical University | Gilthorpe J.,Umea University | van der Maarel J.R.C.,National University of Singapore
PLoS ONE | Year: 2012

Increasing evidence supports the contribution of local inflammation to the development of Alzheimer's disease (AD) pathology, although the precise mechanisms are not clear. In this study, we demonstrate that the pro-inflammatory protein S100A9 interacts with the Aβ1-40 peptide and promotes the formation of fibrillar β-amyloid structures. This interaction also results in reduced S100A9 cytotoxicity by the binding of S100A9 toxic species to Aβ1-40 amyloid structures. These results suggest that secretion of S100A9 during inflammation promotes the formation of amyloid plaques. By acting as a sink for toxic species, plaque formation may be the result of a protective response within the brain of AD patients, in part mediated by S100A9. © 2012 Zhang et al.

Zhu J.-M.,Jinan Military General Hospital | Yu P.-W.,Chongqing Medical University
Molecular Medicine Reports | Year: 2013

T-cell lymphoma invasion and metastasis-inducing factor 1 (Tiam-1) is an important member of the diffuse B-cell lymphoma (Dbl) oncogene family. In a previous study, the overexpression of Tiam-1 protein was identified by immunohistochemistry in human gastric cancer tissues, indicating that Tiam-1 may represent a candidate biomarker of the invasive and metastatic capacity of gastric cancer and for patient prognosis. In the present study, in vitro adhesion selection was used to separate two subpopulations with high (MH) or low (ML) invasive and metastatic potential from the MKN-45 human gastric cancer cell line (M0). A positive correlation was observed between Tiam-l mRNA and protein expression levels and the invasive capacity of the cells using RT-PCR and quantitative cellular-ELISA, respectively. To determine the mechanism by which Tiam-1 affects the invasive capacities of gastric cancer cells, Tiam-1 expression was downregulated in the MH subclone by liposomal transfection of antisense oligodeoxynucleotides (ASODNs). Following 48 h of treatment with ASODNs (0.43 μM), Tiam-1 mRNA transcription and protein expression levels in MH cells was decreased by 80 and 24%, respectively, compared with untreated controls. In addition, the in vitro invasive potential of MH cells was suppressed by 60%. Morphological and ultrastructural observations also demonstrated that ASODN-treated MH cells exhibited a smooth surface with markedly reduced filopodia and microspikes, which resembled M0 and ML cells. In addition, cytoskeletal distribution was markedly altered from disordered to regular with reduced long filament-like structures, projections, pseudopodia on the cell surface and decreased actin bodies in the cytoplasm. Results of the current study indicate that the overexpression of Tiam-1 contributes to the invasive phenotypes of gastric cancer cells. These observations are likely to provide an improved insight into the biological mechanisms of Tiam-1 and promote the development of novel treatment strategies in gastric cancer.

Purpose: This study investigated the role of death receptor 3 (DR3) in experimental autoimmune uveitis (EAU). Methods: EAU was induced in B10.RIII mice by subcutaneous injection of interphotoreceptor retinoid-binding protein (IRBP) 161-180 emulsified with complete Freund's adjuvant and evaluated with clinical and histopathologic observation. Total protein of draining lymph nodes (DLNs) was extracted from the control, EAU, or recovery phase mice. CD4 + T cells were separated from lymphocytes with magnetic-assisted cell sorting. At the same time, some of the CD4 + T cells were cultured with or without recombinant TL1A (rTL1A, the DR3 ligand) for three days, and the supernatants were collected for the interleukin-17 (IL-17) test. DR3 mRNA and protein levels in CD4 + T cells and the endogenous concentration of TL1A in mice DLNs were assessed with real-time PCR or western blotting. Levels of IL-17 in the supernatants were determined with enzyme-linked immunosorbent assay. Results: Histopathological and clinical data revealed severe intraocular inflammation in the immunized mice. The inflammation reached its peak on day 14 in EAU and had resolved in the recovery phase (weeks 4-5 or more after IRBP immunization). CD4 + T cells obtained from EAU (day 7 or 14) had higher levels of DR3 mRNA and protein expression compared with the control group treated with complete Freund's adjuvant alone and the recovery group. However, the DR3 mRNA and protein levels on day 21 in EAU were similar to those observed in the control and recovery groups. The endogenous levels of TL1A were upregulated in EAU, and decreased in the recovery phase mice. Adding rTL1A increased the production of IL-17 by CD4 + T cells isolated from mice DLNs. Moreover, the increased IL-17 levels in the culture supernatant of CD4 + T cells from EAU were much higher than those from the control and recovery phase mice. However, the effects on promoting IL-17 production in TL1A-stimulated CD4 + T cells were similar between the controland recovery groups. Conclusions: Our data suggest that DR3 expression is induced during EAU and may be involved in the development of this disease, possibly by promoting IL-17 secretion. © 2011 Molecular Vision.

Xia Y.,Baylor College of Medicine | Xia Y.,Chongqing Medical University | Jin X.,Baylor College of Medicine | Yan J.,Baylor College of Medicine | And 3 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2014

OBJECTIVE - Recent studies have shown that angiotensin II (Ang II) plays a critical role in the pathogenesis and progression of hypertensive kidney disease. However, the signaling mechanisms are poorly understood. In this study, we investigated the role of CXCR6 in Ang II-induced renal injury and fibrosis. APPROACH AND RESULTS - Wild-type and CXCR6-green fluorescent protein (GFP) knockin mice were treated with Ang II via subcutaneous osmotic minipumps at 1500 ng/kg per minute after unilateral nephrectomy for ≤4 weeks. Wild-type and CXCR6-GFP knockin mice had virtually identical blood pressure at baseline. Ang II treatment led to an increase in blood pressure that was similar between wild-type and CXCR6-GFP knockin mice. CXCR6-GFP knockin mice were protected from Ang II-induced renal dysfunction, proteinuria, and fibrosis. CXCR6-GFP knockin mice accumulated fewer bone marrow-derived fibroblasts and myofibroblasts and produced less extracellular matrix protein in the kidneys after Ang II treatment. Furthermore, CXCR6-GFP knockin mice exhibited fewer F4/80+ macrophages and CD3+ T cells and expressed less proinflammatory cytokines in the kidneys after Ang II treatment. Finally, wild-type mice engrafted with CXCR6+/+ bone marrow cells displayed fewer bone marrow-derived fibroblasts, macrophages, and T cells in the kidney after Ang II treatment when compared with wild-type mice engrafted with CXCR6 bone marrow cells. CONCLUSIONS - Our results indicate that CXCR6 plays a pivotal role in the development of Ang II-induced renal injury and fibrosis through regulation of macrophage and T-cell infiltration and bone marrow-derived fibroblast accumulation. © 2014 American Heart Association, Inc.

Shen J.L.,Chongqing Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2012

To study the impact of resveratrol (RES) on the synthesis of extracellular matrix (ECM) in degenerative nucleus pulposus cells (DNPCs). Human degenerative nucleus pulposus tissues were isolated, identified through monolayer culture, and cultivated in alginate. Primary alginate-cultured DNPCs were irritated by 0, 12.5, 25, 50, 100 and 200 μmol/L RES for 12, 24 and 48 h, respectively. The protein expressions of silent mating type information regulation 2 homolog 1 (SIRT1), Colla2α1 and aggrecan were examined by Western blotting, and the expression level of SIRT1 mRNA was measured through real-time fluorescence quantitative PCR. The cells were transfected by SIRT1-siRNA and cultured in 100 μmol/L RES for 24 h. Then the protein expressions of Colla2α1 and aggrecan were observed. RES up-regulated the expressions of SIRT1 at mRNA and protein levels, and promoted the expression of DNPCs-synthesized ECM, which were significantly different from the control group (P<0.05). After the expression of SIRT1 was silenced by siRNA, RES was added for irritation. The protein expressions of Colla2α1 and aggrecan were significantly reduced in comparison with the control group (P<0.05). RES can stimulate the synthesis of ECM in DNPCs, which exhibits a dose-effect relationship. This regulating effect is related to the activity of SIRT1.

Liu M.,Chongqing Medical University
PloS one | Year: 2014

Wound healing is a multi-phased pathophysiological process requiring chemoattractant receptor-dependent accumulation of myeloid cells in the lesion. Two G protein-coupled formylpeptide receptors Fpr1 and Fpr2 mediate rapid neutrophil infiltration in the liver of Listeria-infected mice by sensing pathogen-derived chemotactic ligands. These receptors also recognize host-derived chemotactic peptides in inflammation and injury. Here we report the capacity of Fprs to promote the healing of sterile skin wound in mice by initiating neutrophil infiltration. We found that in normal miceneutrophils rapidly infiltrated the dermis in the wound before the production of neutrophil-specific chemokines by the injured tissue. In contrast, rapid neutrophil infiltration was markedly reduced with delayed wound closure in mice deficient in both Fprs. In addition, we detected Fpr ligand activity that chemoattracted neutrophils into the wound tissue. Our study thus demonstrates that Fprs are critical for normal healing of the sterile skin wound by mediating the first wave of neutrophil infiltration.

Yan A.,Chongqing Medical University
Medical science monitor basic research | Year: 2013

Integrin â1 subunit and its downstream molecule, focal adhesion kinase (FAK), have been demonstrated to be indispensible to the promotion of cell proliferation and survival and anti-apoptosis in cardiomyocytes via activation of their downstream pro-survival signaling molecule, AKT. As a component of the integrin pathway, Dock180 (dedicator of cytokinesis 1) protein is also thought to be involved in the promotion of cell proliferation and survival and anti-apoptosis in the H9C2 cardiomyocytes. Rat-derived H9C2 cardiomyocytes were transfected with pCXN2-flag-hDock180, a human Dock180 overexpression eukaryotic recombinant plasmid. The rat and human Dock180 mRNA and protein expression, apoptosis and cell proliferation and survival were analyzed in the H9C2 cardiomyocytes treated with either hypoxia/reoxygenation (H/R) or not, respectively. Human Dock180 mRNA overexpression could significantly increase the Dock180 protein expression in the H9C2 cardiomyocytes, no matter whether treated with H/R or not. Dock180 overexpression could promote the cell proliferation and survival and anti-apoptosis, and relieve the cell proliferative and survival inhibition and apoptosis induced by H/R in the H9C2 cardiomyocytes via activation of its downstream pro-survival signaling molecule AKT. Dock180 could act as a pro-survival molecule in H9C2 cardiomyocytes via activation of its downstream pro-survival signaling molecule, AKT.

Cai H.,South China University of Technology | Yang Z.,Chongqing Medical University | Cao X.,Childrens Hospital Boston | Xia W.,VA hospital | Xu X.,Harvard University
IEEE Transactions on Image Processing | Year: 2014

We present a new method in image segmentation that is based on Otsu's method but iteratively searches for subregions of the image for segmentation, instead of treating the full image as a whole region for processing. The iterative method starts with Otsu's threshold and computes the mean values of the two classes as separated by the threshold. Based on the Otsu's threshold and the two mean values, the method separates the image into three classes instead of two as the standard Otsu's method does. The first two classes are determined as the foreground and background and they will not be processed further. The third class is denoted as a to-be-determined (TBD) region that is processed at next iteration. At the succeeding iteration, Otsu's method is applied on the TBD region to calculate a new threshold and two class means and the TBD region is again separated into three classes, namely, foreground, background, and a new TBD region, which by definition is smaller than the previous TBD regions. Then, the new TBD region is processed in the similar manner. The process stops when the Otsu's thresholds calculated between two iterations is less than a preset threshold. Then, all the intermediate foreground and background regions are, respectively, combined to create the final segmentation result. Tests on synthetic and real images showed that the new iterative method can achieve better performance than the standard Otsu's method in many challenging cases, such as identifying weak objects and revealing fine structures of complex objects while the added computational cost is minimal. © 2014 IEEE.

Li J.-X.,Chongqing Medical University | Li J.-X.,U.S. Center for Disease Control and Prevention | Mao Q.-Y.,National Institute for Food and Drug Control | Liang Z.-L.,National Institute for Food and Drug Control | And 2 more authors.
Expert Review of Vaccines | Year: 2014

The widespread epidemics of enterovirus 71 (EV71) seriously affected the Western Pacific Region. Young children, especially those younger than 3 years are the most susceptible population to the EV71-associated diseases. Several Asian countries have begun to focus on the research and development of EV71 vaccines. Five inactivated whole-virus EV71 candidate vaccines (three were manufactured in mainland China based on a C4 genotype strain, one in Taiwan based on a B4 genotype strain and one in Singapore based on a B2 genotype strain) have been assessed in clinical trials. Three candidate vaccines developed in mainland China have already completed Phase III clinical trials recently. The tested EV71 vaccine could provide good efficacy, satisfactory safety, and high immunogenicity. Thus, inactivated EV71 vaccines are expected to become the first available vaccines against EV71 in the near future. © 2014 Informa UK, Ltd.

Gu W.-J.,Guangxi Medical University | Tie H.-T.,Chongqing Medical University | Liu J.-C.,Guangxi Medical University | Zeng X.-T.,Hubei University of Medicine
Critical Care | Year: 2014

Introduction: Ultrasound guidance has emerged as an adjunct for central vein catheterization in both adults and children. However, the use of ultrasound guidance for radial arterial catheterization has not been well established. We conducted a systematic review and meta-analysis to evaluate the efficacy of ultrasound guidance for radial artery catheterization.Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched. Randomized controlled trials (RCTs) comparing ultrasound guidance with other techniques (palpation or Doppler) in adult or pediatric patients requiring radial artery catheterization were included. The primary outcome was first-attempt success.Results: Seven RCTs enrolling 546 patients met the inclusion criteria, and all the selected trials were considered as at high risk of bias. Ultrasound-guided radial artery catheterization was associated with an increased first-attempt success (relative risk (RR) 1.55, 95% confidence interval (CI) 1.02 to 2.35). There was significant heterogeneity among the studies (I2 = 74%). Ultrasound-guided radial artery catheterization in small children and infants also provided an increased chance for first-attempt success (RR 1.94, 95% CI 1.31 to 2.88). Ultrasound guidance further significantly reduced mean attempts to success (weighted mean difference (WMD) -1.13, 95% CI -1.58 to -0.69), mean time to success (WMD -72.97 seconds, 95% CI -134.41 to -11.52), and incidence of the complication of hematoma (RR 0.17, 95% CI 0.07 to 0.41).Conclusions: Ultrasound guidance is an effective and safe technique for radial artery catheterization, even in small children and infants. However, the results should be interpreted cautiously due to the heterogeneity among the studies. © 2014 Gu et al.; licensee BioMed Central Ltd.

Chen J.-F.,University of North Carolina at Chapel Hill | Tao Y.,University of North Carolina at Chapel Hill | Li J.,University of North Carolina at Chapel Hill | Deng Z.,University of North Carolina at Chapel Hill | And 5 more authors.
Journal of Cell Biology | Year: 2010

Skeletal muscle satellite cells are adult stem cells responsible for postnatal skeletal muscle growth and regeneration. Paired-box transcription factor Pax7 plays a central role in satellite cell survival, self-renewal, and proliferation. However, how Pax7 is regulated during the transition from proliferating satellite cells to differentiating myogenic progenitor cells is largely unknown. In this study, we find that miR-1 and miR-206 are sharply upregulated during satellite cell differentiation and downregulated after muscle injury. We show that miR-1 and miR-206 facilitate satellite cell differentiation by restricting their proliferative potential. We identify Pax7 as one of the direct regulatory targets of miR-1 and miR-206. Inhibition of miR-1 and miR-206 substantially enhances satellite cell proliferation and increases Pax7 protein level in vivo. Conversely, sustained Pax7 expression as a result of the loss of miR-1 and miR-206 repression elements at its 3′ untranslated region significantly inhibits myoblast differentiation. Therefore, our experiments suggest that microRNAs participate in a regulatory circuit that allows rapid gene program transitions from proliferation to differentiation. © 2010 Chen et al.

Li B.,Chongqing Medical University
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2011

To evaluate the effectiveness of Confidence high viscosity bone cement system and postural reduction in treating acute severe osteoporotic vertebral compression fracture (OVCF). Between June 2004 and June 2009, 34 patients with acute severe OVCF were treated with Confidence high viscosity bone cement system and postural reduction. There were 14 males and 20 females with an average age of 72.6 years (range, 62-88 years). All patients had single thoracolumbar fracture, including 4 cases of T11, 10 of T12, 15 of L1, 4 of L2, and 1 of L3. The bone density measurement showed that T value was less than -2.5. The time from injury to admission was 2-72 hours. All cases were treated with postural reduction preoperatively. The time of reduction in over-extending position was 7-14 days. All patients were injected unilaterally. The injected volume of high viscosity bone cement was 2-6 mL (mean, 3.2 mL). Cement leakage was found in 3 cases (8.8%) during operation, including leakage into intervertebral space in 2 cases and into adjacent paravertebral soft tissue in 1 case. No clinical symptom was observed and no treatment was performed. No pulmonary embolism, infection, nerve injury, or other complications occurred in all patients. All patients were followed up 12-38 months (mean, 18.5 months). Postoperatively, complete pain relief was achieved in 31 cases and partial pain relief in 3 cases; no re-fracture or loosening at the interface occurred. At 3 days after operation and last follow-up, the anterior and middle vertebral column height, Cobb angle, and visual analogue scale (VAS) score were improved significantly when compared with those before operation (P < 0.05); and there was no significant difference between 3 days and last follow-up (P > 0.05). Confidence high viscosity bone cement system and postural reduction can be employed safely in treating acute severe OVCF, which has many merits of high viscosity, long time for injection, and easy-to-control directionally.

Liu X.,Chongqing Medical University
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology | Year: 2012

To evaluate the changes induced in tumor tissue, the feeding artery, and neovascularization upon pingyangmycin-lipiodol emulsion treatment via transcatheter arterial chemoembolization (TACE) using the rabbit VX2 liver cancer model. The VX2 liver tumor model was established in 28 rabbits, and baseline tumor volume (V1, in mm3) was measured by spiral scan computed tomography (CT). Then, the rabbits were randomly divided into four groups (n = 7 each) and administered intraarterial therapies of: ultrafluid lipoidol embolization (group A); pingyangmycin (group B); pingyangmycin-lipiodol emulsion (group C); or saline (group D). All rabbits were sacrificed seven days later, and the response to therapy was determined by measuring the tumor volume (V2, in mm3), calculating the tumor growth rate, detecting expression of the vascular endothelial growth factor (VEGF) tumor biomarker, and performing histological analysis of the microvessel density (MVD) in the liver. Prior to therapy, the average V1 of the groups was statistically similar (A: 389.8+/-167.3, B: 404.1+/-184.9, C: 355.1+/-158.3, D: 378.1+/-189.0; (F = 0.257, P more than 0.05). In contrast, after therapy the average V2 of the groups was significantly different (A: 922.6+/-32.9, B: 665.9+/-99.9, C: 349.5+/-177.8, D: 1403.5+/-411.2; F = 26.23, P less than 0.05), as was the tumor growth ratio (A: 1.4, B: 0.6, C: -0.02, D: 2.7) and the mean positive ratio of VEGF (A: 57.1%, B: 42.9%, C: 28.6%, D: 100%; F = 8.407, P less than 0.05). MVD was highest in group D and lowest in group C (all, P less than 0.05). Bivariate correlation analysis revealed a positive correlation between VEGF expression and MVD (r = 0.743, P less than 0.01). Pingyangmycin exerts anti-tumor effects in the rabbit VX2 liver cancer model, but is more effective when administered as the combination therapy of pingyangmycin-lipiodol emulsion with TACE.

Wu T.,Chongqing Medical University
Zhonghua er ke za zhi. Chinese journal of pediatrics | Year: 2012

To study the development of anterior fontanel(AF) in children less than 2 years of age. The size of AF of the children under 2 years of age was measured. The criteria were: (1) All the children were singletons and term (37 weeks ≤ gestational age ≤ 40 weeks) at birth, birth weight > 2500 g. (3) Those with intracranial diseases (included trauma and asphyxia) and scalp hematoma were ruled out. (3) Healthy children (without intracranial disease, growth retardation, congenital syndrome or bone metabolic diseases such as rickets). (1) The mean value of AF in neonates was 1.5 (0.3 - 2.5) cm, and the average of the AF at 1 month after birth was 2.2 cm, which was the largest one. The size of AF was 1.0 (0.3 - 2.0) cm at age 12 months, and 0.5 (0.3 - 0.7) cm at 24 months. (2) The percentage for the closure of the AF was 3% at 6 months, 26.5% at 12 months, and 93.0% at 24 months. (3) There were no gender differences in the size of the AF (P > 0.05). And the size of AF was not correlated with the development levels of weight, length, and head circumference (P > 0.05). (1) The size of AF at 1 month was maximum (2.2 cm), and then decreased by years. The AF was almost closed (93%) at 24 months. (2) There were no gender differences in anterior fontanel (P > 0.05). The size of AF was not correlated with the growth of weight, length, and head circumferences (P > 0.05). (3) The fontanel dimensions should be represented by oblique diameters of the fontanel in clinical pediatrics. (4) The AF closure time needs to be further evaluated in normal children.

Zhao J.S.,Chongqing Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2012

Slow transit constipation(STC)is the common type of chronic idiopathic constipation. Due to failure of routine conservative treatment, laxatives abuse is the most choice for majority of the patients, which could damage the enteric nervous system and result in aggravation of constipation. Resection of the slow transit colon is the ultimate option for some patients. It is hard to prevent and treat STC clinically because of the unknown pathophysiologic mechanism. Abnormalities of enteric neurotransmitters such as VIP, SP, NOS and decreased number of interstitial cells of Cajal have been described in the colon of the patients with STC. However, long term application of stimulant laxatives can also result in the almost same changes in the colon. Exploration of the potential relationship among the above reported abnormalities is the direction of future study.

Chen L.Z.,Chongqing Medical University
Zhonghua nei ke za zhi | Year: 2013

To investigate the prevalence, awareness, control status and associated risk factors of hypertension in a rural population in Xianghe county in North China. A total of 830 adults (aged ≥ 35) from Xianghe county were examined during July to August, 2011. Blood pressure was obtained using a standardized sphygmomanometer after a 5-minute sitting rest. Information on gender, age, education level, marital status, smoking, drinking, income, family history of hypertension and use of antihypertensive medications was obtained. A total of 42.4% of all subjects had hypertension. Among those with hypertension, the awareness rate was 54.8% and 50.0% of the patients were taking antihypertensive medication with the control rate of 11.9% [BP < 140/90 mm Hg (1 mm Hg = 0.133 kPa)]. Lower age and education level, lower body mass index, negative family history of hypertension were associated with poor awareness of hypertension and worse compliance with the treatment. Older age, positive family history and alcohol consumption were associated with poor blood pressure control. Hypertension is highly prevalent in Xianghe rural area. The awareness, treatment and control rate are all low. There is an urgent need for comprehensive strategies to improve prevention, screening, and treatment of hypertension in rural China.

Lihua P.,Chongqing Medical University
Cochrane database of systematic reviews (Online) | Year: 2013

Cancer-related pain places a heavy burden on public health with related high expenditure. Severe pain is associated with a decreased quality of life in patients with cancer. A significant proportion of patients with cancer-related pain are under-treated.There is a need for more effective control of cancer-related pain. Spinal cord stimulation (SCS) may have a role in pain management. The effectiveness and safety of SCS for patients with cancer-related pain is currently unknown. This systematic review evaluated the effectiveness of SCS for cancer-related pain compared with standard care using conventional analgesic medication. We also appraised risk and potential adverse events associated with the use of SCS. We searched the following bibliographic databases in order to identify relevant studies: the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Libary (from inception to 2012, Issue 6); MEDLINE; EMBASE; and CBM (Chinese Biomedical Database) (from inception to July, 2012). We also handsearched relevant journals. We planned to include randomised controlled trials (RCTs) that directly compared SCS with other interventions with regards to the effectiveness of pain management. We also planned to include cross-over trials that compared SCS with another treatment. We planned to identify non-randomised controlled trials but these would only be included if no RCTs could be found. The initial search strategy yielded 430 articles. By scrutinising titles and abstracts, we found 412 articles irrelevant to the analytical purpose of this systematic review due to different scopes of diseases or different methods of intervention (intrathecal infusion system; oral medication) or aims other than pain control (spinal cord function monitoring, bladder function restoration or amelioration of organ metabolism). The remaining 18 trials were reviewed as full manuscripts. No RCTs were identified. Fourteen sporadic case reports and review articles were excluded and four before-and-after case series studies (92 participants) were included. Two review authors independently selected the studies to be included in the review according to the pre-specified eligibility criteria. A checklist for methodological quality of non-randomised controlled trials was used (STROBE checklist) and all review authors discussed and agreed on the inclusion of trials and the results of the quality assessment. Four before-and-after case series studies (a total of 92 participants) met our criteria for inclusion. All included trials adopted a visual analogue scale (VAS) to evaluate pain relief. Heterogeneity existed in terms of baseline characteristics, electrode and stimulator parameters, level of implantation and route of implantation; data reporting was different among all trials. In two trials, pain relief was achieved in 76% (48/63) of patients at the end of the follow-up period. In the third trial, pre-procedure VAS was 6 to 9 (mean 7.43 ); the one-month post-implant VAS was 2 to 4 (mean 3.07); the 12-month post-implant VAS was 1 to 3 (mean 2.67). In the fourth trial, the pre-procedure VAS was 6 to 9 (mean 7.07); 1 to 4 (mean 2.67) at one-month; 1 to 4 (mean 1.87) at 12 months. Analgesic use was largely reduced. The main adverse events were infection of sites of implantation, cerebrospinal fluid (CSF) leakage, pain at the sites of electrodes, dislodgement of the electrodes and system failure, however, the incidence in patients with cancer could not be calculated. Since all trials were non-randomised controlled trials, they carried risk of all types of bias. Current evidence is insufficient to establish the role of SCS in treating refractory cancer-related pain. Future randomised studies should focus on the implantation of SCS in patients with cancer-related pain.

Luo Z.,Nanyang Technological University | Ding X.,Chongqing University | Hu Y.,Chongqing University | Wu S.,Nanyang Technological University | And 10 more authors.
ACS Nano | Year: 2013

In order to selectively target malignant cells and eliminate severe side effects of conventional chemotherapy, biocompatible and redox-responsive hollow nanocontainers with tumor specificity were fabricated. The mechanized nanocontainers were achieved by anchoring mechanically interlocked molecules, i.e., [2]rotaxanes, onto the orifices of hollow mesoporous silica nanoparticles via disulfide bonds as intermediate linkers for intracellular glutathione-triggered drug release. The [2]rotaxane employed was mainly composed of U.S. Food and Drug Administration approved tetraethylene glycol chains, α-cyclodextrin, and folic acid. In this study, folate groups on the mechanized hollow nanocontainers act as both the tumor-targeting agents and stoppers of the [2]rotaxanes. Detailed investigations showed that anticancer drug doxorubicin loaded mechanized nanocontainers could selectively induce the apoptosis and death of tumor cells. The drug-loaded nanocontainers enhanced the targeting capability to tumor tissues in vitro and inhibited the tumor growth with minimal side effects in vivo. The present controlled and targeted drug delivery system paves the way for developing the next generation of nanotherapeutics toward efficient cancer treatment. © 2013 American Chemical Society.

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

To infect human umbilical cord mesenchymal stem cells (hUCMSCs) with lentivirus carrying green fluorescence protein (GFP) and observe its effect on octamer binding transcription factor 4 (Oct4) expression. Mesenchymal stem cells isolated from human umbilical cord by tissue adherence method were cultured and detected for the the surface markers by flow cytometry. HUCMSCs were infected with lentivirus carrying GFP at different multiplicity of infection (MOI). GFP expression efficiency was observed using the fluorescence microscope and flow cytometry to obtain optimal MOI value. The experiment included non-transfection group and the GFP transfection group. The effect of GFP lentivirus on cell proliferation was evaluated by MTT. Oct4 expression in hUCMSCs cultured in vitro continuously for 2 and 8 weeks was measured by quantitative reverse transcriptase PCR (qRT-PCR) and immunofluorescence staining. HUCMSCs displayed fusiform shape as fibroblasts in vitro. Flow cytometry revealed that the third-passage cells highly expressed CD29, CD105 and CD90, and lowly expressed CD34 and CD45. At 96 h after infection with GFP lentivirus (MOI=20), GFP positive rate of hUCMSCs was more than 75%, the highest level. MTT showed nearly no change in cell proliferation in the transfected group in comparison with the non-transfection group (P>0.05). The relative expression of Oct4 detected by qRT-PCR in cells cultured for 2 and 8 weeks were 0.9075±0.0124 and 0.8600±0.0135, respectively. Immunofluorescence staining showed that Oct4 expression was localized in the nucleus of cells. Lentivirus-mediated GFP gene can be expressed in hUCMSCs and has no significant effect on the expression of Oct4.

Yu Y.,Chongqing Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2013

To investigate the difference in the therapeutic effects of bone marrow-derived mesenchymal stem cells (BMSCs) of mice from ovariectomy (OVX) group and sham group in treating colitis, and then further study the differences of Fas/FasL expression and downstream T cell migration and apoptosis between the two groups. The osteoporosis animal models were set up by ovariectomy in C57BL6 mice. Meanwhile, 3% dextran sulfate sodium (DSS) was administered for inducing colitis. We compared the therapeutic effects of BMSCs from OVX and sham groups in treating colitis, in addition, detected the expression of Fas/FasL in BMSCsby means of RT-PCR and Western blotting. The ability of BMSCs from the two groups of inducing T cell migaration and apoptosis was also detected. Compared with the sham group, BMSCs from OVX mice expressed a lower level of Fas/FasL and displayed a decreased ability of inducing T cell migration and apoptosis, thus leading to an inferior therapeutic effect in treating colitis in animal models. Fas/FasL expression of BMSCs from the OVX mice is down regulated, thus leading to a decrease of the migration and apoptosis for T cells from mouse colitis.

Sun D.,Chongqing Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2013

To observe the effect of intestinal microflora imbalance caused by antibiotics on the maturity of dendritic cells (DCs) and the expressions of Toll-like receptor 2 (TLR2), TLR4 on DCs in the lung of ovalbumin (OVA)-induced asthma mice. Sixty-four 3-week-old female BALB/c mice were divided randomly into 4 groups, i.e. microbiota imbalance group, microbiota imbalamce combined with OVA challenge group, OVA challenge group and control group, with sixteen mice in each group. On day 14, flow cytometry was adopted to measure the DC subtypes and maturity (MHC-II molecules), and the expressions of TLR2, TLR4 on DCs. The expressions of transforming growth factor-β1 (TGF-β1) and interleukin-6 (IL-6) in situ in lung were detected by immunohistochemical staining. The levels of TGF-β1 and IL-6 in bronchoalveolar lavage fluid (BALF) were examined by ELISA. Compared with control group and OVA challenge group, MHC-II molecules and TLR2, TLR4 expressions on DCs in the lung increased in both microbiota imbalance combined with OVA challenge group and microbiota imbalance group, but they were not significantly different between the two groups (P>0.05). Compared with the other three groups, microbiota imbalance combined with OVA challenge group showed the up-regulated expressions of TGF-β1 and IL-6 proteins in lung and BALF. The alterations in intestinal microflora balance promoted the maturity of DCs and raised the expressions of TLR2 and TLR4 on DCs in mouse lung.

Yu Y.,Chongqing Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2013

To investigate the therapeutic effects of bone marrow-derived mesenchymal stem cells (BMSCs) from C57BL/6 mice on estrogen deficiency induced osteoporosis. Mouse models of estrogen deficiency induced osteoporosis were set up through ovariectomy (OVX) operation and sham operation group was set up as controls. BMSCs were injected via caudal veins. Micro-CT scanning of the femurs was conducted to detect the therapeutic effects of BMSCs. ELISA was used to test the expression level of TNF-α in serum before and after the injection of BMSCs. In the meantime, T cell apoptosis was also tested by flow cytometry combined with FITC-annexin V/7-amino actimycin D staining. Compared with the sham operation group, the trabecular volume (BV/TV), bone mineral density (BMD) and trabecular number (Tb.N/mm) of osteoporosis mice set up by OVX were reduced significantly, and serum TNF-α was up-regulated a little. After the injection of BMSCs, the BV/TV, Tb.Th, Tb.N and T cell apoptosis in the osteoporosis mice increased, and the level of TNF-α decreased. With the ability of immunoregulation, BMSCs might play a critical role in treating estrogen deficiency induced osteoporosis.

Shao B.,Chongqing 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 of receptor activator of nuclear factor-kappa B lig (RANKL), osteoprotegerin (OPG) in bone marrow mesenchymal stem cells (BMSCs) and its impact on osteoclast formation and function in the ovariectomied mice. An animal model of osteoporosis was established by ovariectomy (OVX bilateral ovarian resection) in 8-week-old healthy female mice. The sham group was the 8-week-old healthy female mice with bilateral resection. Macrophages from mice were inducted by M-CSF and RANKL, and co-cultured with the BMSCs collected from mice in the OVX group and sham group, respectively. The osteoclast numbers of the two groups were compared by TRAP staining. The resorption pits were measured by toluidine blue staining. The level of RANKL/OPG expression was detected by RT-PCR and Western blotting. TRAP assay and toluidine blue staining showed that the numbers of osteoclasts and resorption pits in OVX group were more than that in the sham group. The expression of RANKL in BMSC was lower in sham group than that of the OVX group. On the contrary, the expression of OPG in BMSCs was higher in the shame group than that of the OVX group. Expression of RANKL/OPG are regulated by estrogen in BMSCs. RANKL and OPG expression promotes osteoclast development and enhances its function under the condition of estrogen deficiency.

Li W.,Shantou University | Li Q.,Chongqing Medical University
Endocrine Journal | Year: 2012

To clarify the necessity of improving glucose metabolism in polycystic ovary syndrome (PCOS) women as early as possible, 111 PCOS women with normal glucose tolerance and 92 healthy age-matched controls were recruited to investigate glucose levels distribution, insulin sensitivity and β cell function. 91 PCOS women and 33 controls underwent hyperinsulinemic-euglycemic clamp to assess their insulin sensitivity, which was expressed as M value. β cell function was estimated by homeostatic model assessment (HOMA)-β index after adjusting insulin sensitivity (HOMA-βad index). Compared with lean controls, lean PCOS women had similar fasting plasma glucose (FPG), higher postprandial plasma glucose (PPG) (6.03±1.05 vs. 5.44±0.97 mmol/L, P<0.05), lower M value but similar HOMA-βad index, while overweight/ obese PCOS women had higher levels of both FPG (5.24±0.58 vs. 4.90±0.39, P<0.05) and PPG (6.15±0.84 vs. 5.44±0.97 mmol/L, P<0.05), and lower levels of both M value and HOMA-βad index. Linear regression and ROC analysis found BMI was independently associated with M value and HOMA-βad index in PCOS women separately, and the cutoff of BMI indicating impaired β cell function of PCOS women was 25.545kg/m2. In conclusion, insulin resistance and dysregulation of glucose metabolism were common in Chinese PCOS women with normal glucose tolerance. BMI ≥ 25.545kg/m2 indicated impaired β cell function in PCOS women with normal glucose tolerance. © The Japan Endocrine Society.

Grienberger C.,TU Munich | Chen X.,TU Munich | Chen X.,Chongqing Medical University | Konnerth A.,TU Munich
Neuron | Year: 2014

High-frequency bursts of action potentials (APs) are a distinctive form of signaling in various types of mammalian central neurons. In CA1 hippocampal pyramidal neurons invivo, such complex spike bursts (CSs) are detected during various behaviors and are considered to be particularly important for learning- and memory-related synaptic plasticity. Here, we combined whole-cell recordings and two-photon imaging in mouse CA1 pyramidal neurons to investigate the cellular mechanisms underlying CSs invivo. Our results demonstrate that CSs are of synaptic origin, as they require N-methyl-D-aspartate (NMDA) receptor activation. We identify voltage-gated Ca2+ channel-dependent, spike-like depolarizations as integral components of the CSs. These Ca2+ spikes were invariably associated with widespread large-amplitude Ca2+ transients in basal and apical dendrites. Together, our results reveal a type of NMDA receptor-dependent multidendrite Ca2+ spike required for high-frequency bursting invivo. © 2014 Elsevier Inc.

Zhang L.,Leiden University | Zhou F.,Leiden University | Drabsch Y.,Leiden University | Gao R.,Xiamen University | And 7 more authors.
Nature Cell Biology | Year: 2012

The stability and membrane localization of the transforming growth factor-β (TGF-β) type I receptor (TβRI) determines the levels of TGF-β signalling. TβRI is targeted for ubiquitylation-mediated degradation by the SMAD7-SMURF2 complex. Here we performed a genome-wide gain-of-function screen and identified ubiquitin-specific protease (USP) 4 as a strong inducer of TGF-β signalling. USP4 was found to directly interact with TβRI and act as a deubiquitylating enzyme, thereby controlling TβRI levels at the plasma membrane. Depletion of USP4 mitigates TGF-β-induced epithelial to mesenchymal transition and metastasis. Importantly, AKT (also known as protein kinase B), which has been associated with poor prognosis in breast cancer, directly associates with and phosphorylates USP4. AKT-mediated phosphorylation relocates nuclear USP4 to the cytoplasm and membrane and is required for maintaining its protein stability. Moreover, AKT-induced breast cancer cell migration was inhibited by USP4 depletion and TβRI kinase inhibition. Our results uncover USP4 as an important determinant for crosstalk between TGF-β and AKT signalling pathways. © 2012 Macmillan Publishers Limited. All rights reserved.

Guo C.,Chongqing University | Chen C.,Chongqing University | Luo Z.,Chongqing Medical University
International Journal of Electrochemical Science | Year: 2013

There is a growing interest in oxygen electrochemistry as conversions between O2 and H2O play an important role in a variety of new energy technologies. Here we design the nitrogen-containing carbon material by using two-step carbonization of hemolymph protein to study the process of oxygen reduction catalysis in alkaline media. The structural and chemical properties of carbon material was studied using the X-ray diffraction, scanning electron microscopy and X-ray photoelectron spectroscopy, and its catalytic activity for the oxygen reduction reaction (ORR), methanol-tolerant performance and long-term stability were evaluated by linear sweeping voltammetry and amperometric I-t curve. The results indicate that the ORR onset potential for carbon material is approximately 0.05 V (vs. Hg/HgO) being close to the commercial Pt/C catalyst. An important finding is the methanol-tolerant performance and stability of carbon material has outperformed the Pt/C catalyst. We also propose the pyrrolic- and pyridinic-nitrogen groups may be the catalytic active sites for the ORR. This work would stimulate ones to develop the activated carbon materials by using native proteins. © 2013 by ESG.

Objective: To construct and express the recombinant plasmid pET28α-Sj26GST-Sj32 of Schistosoma japonicum (Sj) in Escherichia coli BL21 (DE3). Methods: Total RNA was extracted from Sj adult worms by ultrasound-breaking, SJ26GST and Sj32 antigen gene was respectively amplified by RT-PCR from the total RNA; Sj26GST-Sj32 fusion gene obtained with gene splicing by overlap extension(SOEing) was cloned into prokaryotic expression plasmid pET28α and transformed into Escherichia coli BL2 (DE3) to construct pET28α-Sj26GST-Sj32; BL21 (pET28α-Sj26GST-Sj32) was induced with isopropyl-β-D-thiogalactopyranosid (IPTG), and the expressed products were analyzed and identified by sodium dodecyl sulfate Polyacrylamide gel electropheresis (SDS-PAGE) and Western blotting. Results: The 1991 bp Sj26GST-Sj32 fusion gene was successfully amplified by gene SOEing and cloned into pET28α by restriction analysis and PCR identification, the recombinant plasmid pET28α-Sj26GST-Sj32 was successfully constructed; the relative molecular mass of the expressed recombinant protein was approximately 69 × 103 by SDS-PAGE, and the amount of the expressed protein was 25% of the total bacterial proteins; the fusion protein could be recognized by sera from rabbits infected with Sj by Western blotting. Conclusions: The recombinant plasmid pET28α-Sj26GST-Sj32 is successfully constructed and highly expressed in Escherichia coli in fused form with His-tag, and the expressed fusion protein shows specific antigenicity.

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

To elucidate the mechanism of ethyl pyruvate (EP) inhabit high mobility group protein B1 (HMGB1)expression and releasing in macrophage induced by lipopolysaccharide(LPS). The murine macrophage-like cell line RAW264.7 cultured in vitro divided into LPS group and LPS+EP group. The expression of HMGB1 mRNA in cultured cell was determined by RT-PCR. The cytoplasmic and nuclear HMGB1 levels were detected by Western blot. The contents of HMGB1 and TNF-α and IL-6 protein in cultured cells supernatant were detected by ELISA. Immunocytochemistry and confocal laser-scanning microscopy were used to confirm the relocation and distribution of intracellular HMGB1 protein in RAW264.7 cells. HMGB1 mRNA expression in the LPS+EP group was significantly lower than in LPS alone, at 24, 36 and 48 hours. In the LPS+EP stimulation group, the cytoplasm stained weakly while the nuclear stain was stronger than that of the LPS group at the same time points. Both TNF-α and IL-6 levels in LPS+EP group were significantly lower than those in the LPS group at the same time points. EP also effectively prevented the release of HMGB1 protein. EP inhibits HMGB1 expression and release from LPS-stimulated macrophages.

Yin J.P.,Chongqing Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To characterize dark-adapted and light-adapted oscillatory potentials (OPs) in human electroretinogram (EGR) elicited by flashing light stimulation of the same intensity. Dark- and light-adapted ERGs of normal eyes were studied. The frequency spectra of the extracted dark-adapted OPs and light-adapted OPs were analyzed by a fast Fourier transform. The peak frequency, latency and total power of the OPs were determined. The averaged peak frequency, latency, and power of the dark-adapted OPs was 125.3∓9.93 Hz, 41.7∓3.56 ms, and 9.25∓5.55 (V·s)(2), as compared with 79.5∓6.79 Hz, 50.8∓5.36 ms, and 3.56∓2.18 (V·s)(2) for light-adapted Ops, respectively, showing significant differences in the parameters between dark- and light-adapted Ops (P<0.001). Compared with dark-adapted OPs, light-adapted Ops is characterized by a lower peak frequency and a lower power with a prolonged latency.

Yan J.M.,Chongqing Medical University
Zhonghua er ke za zhi. Chinese journal of pediatrics | Year: 2011

To compare the growth and symptom remission of infants with cow's milk protein allergy, who were fed with an amino acid formula, an extensively hydrolyzed formula or soy formula. Infants who were diagnosed as cow's milk protein allergy and can not be breastfed were enrolled in the intervention group, and were assigned to three special formulae (amino acid formula, extensively hydrolyzed formula or soy formula ) according to the will of parents from March 2009 to March 2010 (n = 74). A non-randomized control group was made up of age-matched healthy children (n = 21). Anthropometric measurements and symptoms were evaluated after 30, 60, 90, and 180 days. The differences of physical growth and the therapeutic effects among each group were calculated by SPSS 13.0 package. After 180 days follow-up, the weight for age Z score and length for weight Z score were -0.43 +/- 0.88 and -0.31 +/- 0.78 in patients fed with soy formula substitute, which were significantly lower than those of patients fed with amino acid formula (0.11 +/- 0.77, 0.20 +/- 0.69) , extensively hydrolyzed formula (0.10 +/- 0.62, 0.18 +/- 0.70) and control group (0.22 +/- 0.54, 0.22 +/- 0.64) (P<0.05). However, there were no significant differences in physical growth among patients fed with amino acid formula, extensively hydrolyzed formula and control group (P>0.05). Moreover, no significant difference was found in length for age and head circumference for age among four groups (P>0.05). All hypoallergenic formulae were much helpful in remission of the symptoms of eczema (P<0.05). However, amino acid formula and extensively hydrolyzed formula were more effective and rapid in relieving symptoms than soy formula (1 mo vs 2 mo) (P = 0.003). Both amino acid formula and extensively hydrolyzed formula can maintain the normal growth of infants with cow's milk protein allergy. While, the growth of patients fed with soy formula was significantly slower than that of the other three groups. All hypoallergenic formulae can be effective in relieving allergy symptoms, and amino acid formula or extensively hydrolyzed formula seems to be superior to soy formula.

Dal Pra I.,University of Verona | Chiarini A.,University of Verona | Gui L.,Chongqing Medical University | Chakravarthy B.,National Research Council Canada | And 4 more authors.
Neuroscientist | Year: 2015

Evidence has begun emerging for the "contagious" and destructive Aβ42 (amyloid-beta42) oligomers and phosphorylated Tau oligomers as drivers of sporadic Alzheimer's disease (AD), which advances along a pathway starting from the brainstem or entorhinal cortex and leading to cognition-related upper cerebral cortex regions. Seemingly, Aβ42 oligomers trigger the events generating the neurotoxic Tau oligomers, which may even by themselves spread the characteristic AD neuropathology. It has been assumed that only neurons make and spread these toxic drivers, whereas their associated astrocytes are just janitorial bystanders/scavengers. But this view is likely to radically change since normal human astrocytes freshly isolated from adult cerebral cortex can be induced by exogenous Aβ25-35, an Aβ42 proxy, to make and secrete increased amounts of endogenous Aβ42. Thus, it would seem that the steady slow progression of AD neuropathology along specific cognition-relevant brain networks is driven by both Aβ42 and phosphorylated Tau oligomers that are variously released from increasing numbers of "contagion-stricken" members of tightly coupled neuron-astrocyte teams. Hence, we surmise that stopping the oversecretion and spread of the two kinds of "contagious" oligomers by such team members, perhaps via a specific CaSR (Ca2+-sensing receptor) antagonist like NPS 2143, might effectively treat AD. © The Author(s) 2014.

Zhou L.,Chongqing Medical University
Zhonghua fu chan ke za zhi | Year: 2013

To analyze the clinical characteristics and perinatal outcome of early-onset intrahepatic cholestasis of pregnancy (ICP). A total of 305 ICP cases were collected in the First Affiliated Hospital of Chongqing Medical University between June 2006 and May 2012. According to the onset time of ICP, patients were divided into early-onset ICP group (onset time < 28 gestational weeks) and late-onset ICP group (onset time ≥ 28 gestational weeks). The late-onset ICP group was further divided into 28 - 31(+6) gestational weeks and ≥ 32 gestational weeks according to the onset time. The biochemical indices and perinatal outcome of each group were assessed. (1) When the diagnosis was made for the first time, the maternal serum concentrations of total bile acid (TBA) and total bilirubin (TBIL) in early-onset ICP group were (41 ± 9) and (32 ± 9) μmol/L, respectively; while TBA and TBIL in late-onset ICP group were (32 ± 6) and (22 ± 9) μmol/L, and the difference between the two groups was statistically significant (P < 0.05). (2) There was no significant difference in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between early-onset ICP group and late-onset ICP group (P > 0.05). The ALT of early-onset ICP group and late-onset ICP group were (159 ± 50) and (145 ± 52) U/L, respectively; and AST were (151 ± 49) and (138 ± 44) U/L, respectively. (3) The early-onset ICP group had significant higher (P < 0.05) incidence of meconium staining (18.8% vs. 7.4%), fetal distress (22.9% vs. 8.9%), newborn asphyxia (14.6% vs. 5.4%), premature delivery (33.3% vs. 15.6%), developing into severe ICP (41.7% vs. 25.3%) and cesarean section (91.7% vs. 78.6%) when compared to the late-onset ICP group. No significant difference in the incidence of premature delivery, developing into severe ICP and cesarean section was found between the two types of late-onset ICP. (4) There was significant differences in average birth weight and gestational weeks at delivery between the two groups [early-onset ICP group: (3113 ± 443) g and (36.3 ± 2.6) weeks]; late-onset ICP group: [(3513 ± 450) g and (37.7 ± 1.6) weeks]. The early-onset ICP patients presented worse clinical manifestations than late-onset ICP patients, and early-onset ICP is more likely to lead to premature delivery and fetal distress.

He L.,Chongqing University | Bai Q.,Chongqing Medical University | Tang L.,Chongqing University
Current Stem Cell Research and Therapy | Year: 2015

Alternative splicing (AS) generates multiple mature mRNAs from a single pre-mRNA, so AS is the main contributor for the diversity of the proteins, participating in most of the cellular processes. For pluripotent stem cells (PSCs), great effort has been made to search for pluripotency-related genes and their regulatory mechanisms. However, the sophisticated regulation still remains to be clear. Recent studies indicate that stem cells undergo a unique AS pattern and have a different protein expression profile from differentiated cells, giving a new clue that AS switching or AS itself may play a significant role in the processes of differentiation and somatic reprogramming. Indeed, accumulating evidences prove that AS plays critical roles in maintaining pluripotent homeostasis in PSCs. In this review, we summarized recent researches on AS in ESCs and iPSCs, including some distinct AS events in pluripotent cells, and then discussed the new progress on mechanisms for AS in ESCs and iPSCs differentiation and somatic reprogramming. © 2015 Bentham Science Publishers.

Tian Z.,Chongqing Medical University
Current cancer drug targets | Year: 2010

Pokemon gene has crucial but versatile functions in cell differentiation, proliferation and tumorigenesis. It is a master regulator of the ARF-HDM2-p53 and Rb-E2F pathways. The facts that the expression of Pokemon is essential for tumor formation and many kinds of tumors over-express the Pokemon gene make it an attractive target for therapeutic intervention for cancer treatment. In this study, we used an RNAi strategy to silence the Pokemon gene in a cervical cancer model. To address the issues involving tumor specific delivery and durable expression of siRNA, we applied the Arg-Gly-Asp (RGD) peptide ligand and polylysine (K(18)) fusion peptide to encapsulate a recombinant retrovirus plasmid expressing a siRNA targeting the Pokemon gene and produced the 'mimoretrovirus'. At charge ratio 2.0 of fusion peptide/plasmid, the mimoretrovirus formed stable and homogenous nanoparticles, and provided complete DNase I protection and complete gel retardation. This nanoparticle inhibited SiHa cell proliferation and invasion, while it promoted SiHa cell apoptosis. The binding of the nanoparticle to SiHa cells was mediated via the RGD-integrin α(v)β(3) interaction, as evidenced by the finding that unconjugated RGD peptide inhibited this binding significantly. This tumor-targeting mimoretrovirus exhibited excellent anti-tumor capacity in vivo in a nude mouse model. Moreover, the mimoretrovirus inhibited tumor growth with a much higher efficiency than recombinant retrovirus expressing siRNA or the K(18)/P4 nanoparticle lacking the RGD peptide. Results suggest that the RNAi/RGD-based mimoretrovirus developed in this study represents a novel anti-tumor strategy that may be applicable to most research involving cancer therapy and, thus, has promising potential as a cervical cancer treatment.

Samanta D.,Johns Hopkins University | Gilkesa D.M.,Johns Hopkins University | Chaturvedia P.,Johns Hopkins University | Xiang L.,Johns Hopkins University | And 2 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

Triple negative breast cancers (TNBCs) are defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 expression, and are treated with cytotoxic chemotherapy such as paclitaxel or gemcitabine, with a durable response rate of less than 20%. TNBCs are enriched for the basal subtype gene expression profile and the presence of breast cancer stem cells, which are endowed with self-renewing and tumor-initiating properties and resistance to chemotherapy. Hypoxia-inducible factors (HIFs) and their target gene products are highly active in TNBCs. Here, we demonstrate that HIF expression and transcriptional activity are induced by treatment of MDA-MB-231, SUM-149, and SUM-159, which are human TNBC cell lines, as well as MCF-7, which is an ER+/PR+ breast cancer line, with paclitaxel or gemcitabine. Chemotherapy-induced HIF activity enriched the breast cancer stem cell population through interleukin-6 and interleukin-8 signaling and increased expression of multidrug resistance1. Coadministration of HIF inhibitors overcame the resistance of