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Tianjin, China

Tianjin Medical University was founded in 1951; was the first medical institution approved by the State Council of the People's Republic of China. Hsien-I Chu, a renowned endocrinologist, was the first president of the university. The current president is Yongfeng Shang.In December 1993, with the approval of the State Education Council, the Tianjin Medical College and the Tianjin Second Medical College were integrated into the Tianjin Medical University. In December 1996, the university was accepted into Project 211, so it became one of the 97 key institutions in which there are 9 medical institutions that will be constructed emphatically by the State.In 1981, the university was approved by the Academic Degree Committee of State Council to confer the Doctorate Degree, Master's Degree and Bachelor's Degree and in 1988, was permitted to set up seven-year medical program.It is listed in International Medical Education Directory . Wikipedia.

Li N.,Tianjin Medical University
Clinical Journal of Pain | Year: 2015

BACKGROUND:: Several mechanisms of remifentanil-induced hyperalgesia in spinal cord mainly have been explained such as N-methyl-D-aspartate receptors (NMDAR) activation, but the mechanism in dorsal root ganglion (DRG) is poorly understood. It has been reported that CCL3 may be a regulator in both inflammatory pain and hyperalgesia. So, in this paper we explored whether CCL3 and CCR5, the mainly receptor of CCL3, play a role in the remifentanil-induced hyperalgesia in DRG by using a rat model with remifentanil administration. METHODS:: The von Frey test and hot plate test were performed to measure the different threshold to evaluate mechanical and thermal hyperalgesia. Real time polymerase chain reaction and western blot analysis were used to evaluate time course of CCL3 and CCR5 expression in DRG after remifentanil infusion. The changes of glial cells and the expression of CCL3 and CCR5 were detected by immunofluorescence assay. Lastly, intrathecal injection of CCL3-neutralizing antibody and maraviroc, the CCR5 antagonists, were used sevoflurane to confirm the role of CCL3/CCR5 signaling in the rat model of remifentanil-induce hyperalgesia. RESULTS:: Remifentanil infusion profoundly increased thermal and mechanical hyperalgesia from 2 hours to 48 hours according to paw withdrawal latency (PWL) and paw withdrawal thresholds (PWT) (mean±SD, hyperalgesia vs. control, 17.4±0.91▒s vs. 8.5±1.46▒s; 20.1±0.32▒g vs. 9.6±0.5▒g, n=8). Moreover, the expression of mRNAs and proteins of CCL3 and its receptor CCR5 in DRG were dramatically increased in rats after remifentanil infusion as compared with the normal saline group. We also found that CCL3 and CCR5 were co-localized with glial cells or neurons. Furthermore, intrathecal injection of CCL3-neutralizing antibody (mean±SD, hyperalgesia vs. control, 17.4±0.91▒s vs. 8.5±1.46▒s; 20.1±0.32▒g vs. 9.6±0.5▒g, n=5)and maraviroc(mean±SD, hyperalgesia vs. control, 17.4±0.91▒s vs. 8.5±1.46▒s; 20.1±0.32▒g vs. 9.6±0.5▒g, n=5) were able to suppress remifentanil related thermal and mechanical hyperalgesia according to behavioral test. CONCLUSIONS:: The results highlighted the fact that CCL3 and its receptor CCR5 in DRG might contribute to remifentanil-induced hyperalgesia. Thus CCL3/CCR5 signaling may be further considered in the development of new therapeutic strategies. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Sajjadi S.,Kings College London | Chen Y.,Tianjin Medical University
European Polymer Journal | Year: 2015

Abstract The minimum size achievable by semicontinuous monomer-starved emulsion polymerization has been explored. Styrene was used as the monomer, and potassium persulfate and sodium dodecylsulfate were used as initiator and surfactant, respectively. The rate of monomer addition (Ra), surfactant concentration ([S]) and reaction temperature (T) were varied. The variations in the number of particles (Np) with these variables were confined to the equation Np=k(as[S])RI2/3Ra-2/3, if micelles were fully depleted by the end of monomer addition. However, the particle number approached a plateau at very low Ra and high [S], and a maximum at a high T followed by a sudden fall. These features were attributed to the depletion of either monomer or radical prior to that of micelles. The conditions for achieving the minimum particle size were explored. Using extremely low Ra, particles with diameter close to the size of micelles were detected in the early stage of reactions, which only grew a little with time. Under such conditions, it is possible to supress particle growth so that the average size of particles remains close to that of micelles. © 2015 Elsevier Ltd.

In present work, influences of molar fraction and acyl chain length of lipids on the interaction between cationic nanoparticles (NP) and the lipid bilayer have been investigated via coarse-grained molecular dynamics simulations. It is found that the participation of the anionic lipids improves the NP-membrane interaction; however in the case of PC/PG mixed membrane, the bending of the membrane is merely dependent on the increase of molar fraction of charged lipids in the heterogeneous membrane because of the relatively slow diffusion of lipids in the membrane and the repulsive effect between charged lipids against their further aggregation around the NP. Besides, it is also found that the acyl chain length of lipids plays a crucial role on the NP-induced structural variation and morphology transition of the lipid bilayer. As a charged NP attaches to the membrane, a thin DPPC/POPG membrane is more vulnerable to these extracellular disturbances than a relatively thick DSPC/DOPG membrane. Different from the NP-induced lipid eyelid structure budding from the DSPC/DOPG membrane, the adsorption of a NP disrupts the DPPC/POPG membrane and evokes a water pore in the lipid bilayer, implying the translocation mechanism of a NP across the membrane could be mediated by the acyl chain length of lipids. These results are beneficial for an further understanding in the translocation mechanism of nanocarriers as drug delivery vehicles for cancer therapeutics. © The Royal Society of Chemistry 2015.

Xu Y.,Institute of Cardiovascular | Sharma D.,Tianjin Medical University | Li G.,Institute of Cardiovascular | Liu Y.,Institute of Cardiovascular
Medical Hypotheses | Year: 2013

Atrial fibrillation (AF), the most common sustained arrhythmia associated with substantial cardiovascular morbidity and mortality with stroke being the most critical complication. Most frequently, AF occurs in conjunction with other cardiovascular disease, such as hypertension, ischemic heart disease, valve disease or cardiac failure. Role of atrial remodeling has emerged as the new pathophysiological mechanism of atrial fibrillation. Experimental and clinical studies point at two major mechanisms involved in the intrinsically progressive nature of AF. The first consists of a change in the electrical properties of the atrium, notably a shortening of the AERP and a loss of rate adaptation, and hence was named electrical remodeling. Furthermore, based on data from is experimental models, it has been considered that AF is also associated with elaborate adaptive and maladaptive changes in tissue and cellular architecture. By parallel, this type of change was denominated structural remodeling. Together, these mechanisms will increase the probability of generating multiple atrial wavelets by enabling rapid atrial activation and dispersion of refractoriness. © 2012 Elsevier Ltd.

Li B.,Tianjin Medical University | Urban J.P.G.,University of Oxford | Yu J.,University of Oxford
Journal of Anatomy | Year: 2012

We investigated the distribution of fibrillin-2 and LTBP-2 (latent TGF-β binding protein-2) in the intervertebral disc of the adult bovine tail. The association of fibrillin-2 and of LTBP-2 with fibrillin-1 was examined by dual immunofluorescence staining. Both fibrillin-2 and LTBP-2 were found extensively distributed in all regions of the disc with the organisation of the network varying significantly region to region. In the outer annulus fibrosus (OAF) both fibrillin-2 and LTBP-2 co-localised with fibrillin-1 forming fibres running parallel to the collagen fibres of the lamellae with the microfibrillar network staining densely in between the adjacent lamellae and also at the boundaries of the collagen bundle compartments. In the inner annulus fibrosus (IAF) and nucleus pulposus (NP), co-localised fibrillin-1,2 and LTBP-2 formed a chondron-like structure around the cell. By contrast, the inter-territorial matrix of the IAF and NP contained a dense network of fibrillin-2 but only sparse/filamentous fibres of fibrillin-1 and LTBP-2. Dual immunostaining revealed that in this region, fibrillin-2 was highly colocalised with elastin. The LTBP-2 network co-localised well with that of fibrillin-1 in all regions and indeed is reported to bind strongly to fibrillin-1. However, interestingly LTBP-2 but not fibrillin-1 or fibrillin-2 was removed by hyaluronidase but not collagenase pre-digestion. Our results suggest that fibrillin-2 and LTBP-2 could play an important role in disc function. © 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society.

Liu B.N.,Tianjin Medical University
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2012

To investigate the expressions of STAT5 phosphorylation in CD34(+)CD38(-)CD123(+) bone marrow cells of the patients with myelodysplastic syndromes (MDS), and then evaluate the level of activation of STAT5 associated with cell proliferation in MDS clone cells. The bone marrow mononuclear cells (BMMNC) were extracted from 36 MDS patients and 14 normal controls. The mean fluorescence intensities (MFI) of phosphorylated STAT5(P-STAT5) in CD34(+)CD38(-)CD123(+) and CD34(+)CD38(-)CD123(-)cells, with or without the stimulation of 10 U/ml EPO, were examined by flow cytometry (FCM). Without stimulation, the P-STAT5 MFI in CD34(+)CD38(-)CD123(+) cells of low/high risk MDS patients was 113.71 ± 67.22/173.05 ± 102.78, which was significantly higher than that of CD34(+)CD38(-)CD123(-) cells (58.84 ± 27.51/68.99 ± 50.42, P < 0.01, P < 0.05) and the normal controls CD34(+)CD38(-)CD123(-) cells (63.06 ± 21.06, P < 0.05), there was no significant difference between the CD34(+)CD38(-)CD123(-) cells of MDS patients and the normal control CD34(+)CD38(-)CD123(-) cells; With the EPO stimulation, the P-STAT5 MFI in CD34(+)CD38(-)CD123(+) cells of low/high risk MDS patients was 144.04 ± 58.11/239.45 ± 152.05, which was significantly higher than that of CD34(+)CD38(-)CD123(-) cells (68.41 ± 25, 10/64.21 ± 23.43, P < 0.01) and the normal controls CD34(+)CD38(-)CD123(-) cells (75.21 ± 27.02, P < 0.01), there was no significant difference between the CD34(+)CD38(-)CD123(-) cells of MDS patients and the normal control CD34(+)CD38(-)CD123(-) cells; The P-STAT5 MFI in the CD34(+)CD38(-)CD123(+) cells of low/high risk MDS patients with or without EPO stimulation were 21.80/28.86, which was significantly higher than that of CD34(+)CD38(-)CD123(-) cells (7.42/5.50, P < 0.01, P < 0.05) and the normal controls CD34(+)CD38(-)CD123(-) cells (6.39, P < 0.05), there was no significant difference between the CD34(+)CD38(-)CD123(-) cells of MDS patients and the normal controls CD34(+)CD38(-)CD123(-) cells; There was no significant difference of P-STAT5 MFI with or without EPO stimulation and the increased P-STAT5 MFI between the CD34(+)CD38(-)CD123(+) cells of low and high risk MDS. STAT5 associated with cell proliferation was activated in CD34(+)CD38(-)CD123(+) bone marrow cells in MDS, which had more significant reactions to EPO than CD34(+)CD38(-)CD123(-) cells, indicating that CD34(+)CD38(-)CD123(+) bone marrow cells might be the real malignant MDS clone cells in MDS.

Pu Y.,City University of New York | Chen J.,Tianjin Medical University | Wang W.,City University of New York
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2014

The scattering coefficient, μs, the anisotropy factor, g, the scattering phase function, p(θ), and the angular dependence of scattering intensity distributions of human cancerous and normal prostate tissues were systematically investigated as a function of wavelength, scattering angle and scattering particle size using Mie theory and experimental parameters. The Matlab-based codes using Mie theory for both spherical and cylindrical models were developed and applied for studying the light propagation and the key scattering properties of the prostate tissues. The optical and structural parameters of tissue such as the index of refraction of cytoplasm, size of nuclei, and the diameter of the nucleoli for cancerous and normal human prostate tissues obtained from the previous biological, biomedical and bio-optic studies were used for Mie theory simulation and calculation. The wavelength dependence of scattering coefficient and anisotropy factor were investigated in the wide spectral range from 300 nm to 1200 nm. The scattering particle size dependence of μs, g, and scattering angular distributions were studied for cancerous and normal prostate tissues. The results show that cancerous prostate tissue containing larger size scattering particles has more contribution to the forward scattering in comparison with the normal prostate tissue. In addition to the conventional simulation model that approximately considers the scattering particle as sphere, the cylinder model which is more suitable for fiber-like tissue frame components such as collagen and elastin was used for developing a computation code to study angular dependence of scattering in prostate tissues. To the best of our knowledge, this is the first study to deal with both spherical and cylindrical scattering particles in prostate tissues. © 2014 SPIE.

Zheng Y.-Z.,Tianjin Medical University
Chinese Journal of Ophthalmology | Year: 2013

Uveitis is a group of common sight-threatening intraocular inflammatory diseases. Besides of few patients caused by infectious agents, most of patients caused by the autoimmune reactions. In recent years, the basic and clinical researches in the immunology of uveitis had many advances. The complex immunologic mechanisms in uveitis were explained from the levels of cellular and molecular immunology. And the theoretical basis on the treatment of uveitis was established. But there are some unresolved questions existed in the fields of uveitis researches, such as the mechanisms of body defense system to prevent the intraocular inflammation, the pathogenesis of infection that causes the autoimmune response and the autoimmune uveoretinitis, the susceptible gene of uveitis and the related factors associated with occurrence and chronic in uveitis. The deeper studies on these questions will be benefit to the diagnosis and treatment of human refractory uveitis. Copyright © 2013 by the Chinese Medical Association.

Cai N.,Tianjin Medical University | Li W.,Northeastern University China | Jing Y.,Northeastern University China
Nonlinear Dynamics | Year: 2011

In this paper, the generalized synchronization of chaotic systems with different order is studied. The definition of finite-time generalized synchronization is put forward for the first time. Based on the finite-time stability theory, two control strategies are proposed to realize the generalized synchronization of chaotic systems with different order in finite time. Besides the relation between the parameter β, the initial states of systems and the convergent time were obtained. The corresponding numerical simulations are presented to demonstrate the effectiveness of proposed schemes. © 2010 Springer Science+Business Media B.V.

Hou L.,Northwestern University | Zhang X.,Northwestern University | Wang D.,Northwestern University | Wang D.,Tianjin Medical University | Baccarelli A.,Harvard University
International Journal of Epidemiology | Year: 2012

Every year more than 13 million deaths worldwide are due to environmental pollutants, and approximately 24% of diseases are caused by environmental exposures that might be averted through preventive measures. Rapidly growing evidence has linked environmental pollutants with epigenetic variations, including changes in DNA methylation, histone modifications and microRNAs.Environ mental chemicals and epigenetic changes All of these mechanisms are likely to play important roles in disease aetiology, and their modifications due to environmental pollutants might provide further understanding of disease aetiology, as well as biomarkers reflecting exposures to environmental pollutants and/or predicting the risk of future disease. We summarize the findings on epigenetic alterations related to environmental chemical exposures, and propose mechanisms of action by means of which the exposures may cause such epigenetic changes. We discuss opportunities, challenges and future directions for future epidemiology research in environmental epigenomics. Future investigations are needed to solve methodological and practical challenges, including uncertainties about stability over time of epigenomic changes induced by the environment, tissue specificity of epigenetic alterations, validation of laboratory methods, and adaptation of bioinformatic and biostatistical methods to high-throughput epigenomics. In addition, there are numerous reports of epigenetic modifications arising following exposure to environmental toxicants, but most have not been directly linked to disease endpoints. To complete our discussion, we also briefly summarize the diseases that have been linked to environmental chemicals-related epigenetic changes. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2011; all rights reserved.

Zhang W.,Tianjin Medical University
National Medical Journal of China | Year: 2015

Objective: To evaluate the efficacy of limited margins intensity-modulated radiotherapy (IMRT) with temozolomide chemotherapy in patients with malignant glioma, and explore the prognostic factors of malignant glioma. Methods: A total of 33 whole-resected patients, 14 partial-resected patients and 3 biopsied patients were randomly divided into limited margins group and routine margins group. The patients were treated with IMRT and temozolomide concurrent chemotherapy, subsequently adjuvant chemotherapy. Then all the patients were evaluated 2 months later after concurrent chemoradiotherapy. Progression-free survival in 1 year (PFS-1), progress free survival rate in 1 year (PFSR-1) and 1 year survival rate (SR-1) were recorded. All the possible prognostic factors were analyzed. Results: Routine margins group: complete response (CR) 19, partial response (PR) 2, stable disease (SD) 2, progressive disease (PD) 2; Limited margins group; CR 16, PR 6, SD 1, PD 2. Mean PFS-1 of the two groups were 11.64 and 11.36 months, respectively. PFSR-1 were 84% in routine margins group and 80% in limited margins group. SR-1 of two groups were both 100%. Surgery results and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status were correlated with immediate-term prognosis by either univariate or multivariate analysis. Both surgery results and immediate-term prognosis were relevant factors to PFS-1. Progression sites in two groups had no statistical difference by analysis. Conclusions: Both groups gained favorable results, and limited margins doesn't increase local failures. Surgery results are important prognostic factors to immediate-term prognosis and PFS-1. © 2015, Chinese Medical Association. All rights reserved.

Duan X.-F.,Tianjin Medical University
Cancer Biology and Medicine | Year: 2013

Splenic metastasis is generally not a common clinical event. However, metastasis to the spleen from adrenal pheochromocytoma is extremely rare and has not been reported in literature. This report presents a case of a 58 year-old male patient who developed spleen-only metastases in July 2007. The patient had a previous history of left epinephroectomy for adrenal pheochromocytoma in January 2003. Abdominal computed tomography demonstrated multiple enhancing lesions suggestive of metastases; thus splenectomy was performed. Pathological examinations confirmed the diagnosis of splenic metastases from pheochromocytoma. The patient was alive without recurrence 48 months after splenectomy. This study is the first report on splenic metastasis from previous adrenal pheochromocytoma, and long-term survival was achieved by splenectomy. A history of malignancy indicates a high index of suspicion for splenic metastasis, and long-term survival can be achieved by splenectomy for spleen-only metastasis. Copyright © 2013 by Cancer Biology & Medicine.

Song X.-F.,Tianjin University of Technology | Jin C.-X.,Tianjin Medical University | Yin L.,James Cook University
Journal of the Mechanical Behavior of Biomedical Materials | Year: 2015

Enamel cutting using dental handpieces is a critical process in tooth preparation for dental restorations and treatment but the machinability of enamel is poorly understood. This paper reports on the first quantitative assessment of the enamel machinability using computer-assisted numerical control, high-speed data acquisition, and force sensing systems. The enamel machinability in terms of cutting forces, force ratio, cutting torque, cutting speed and specific cutting energy were characterized in relation to enamel surface orientation, specific material removal rate and diamond bur grit size. The results show that enamel surface orientation, specific material removal rate and diamond bur grit size critically affected the enamel cutting capability. Cutting buccal/lingual surfaces resulted in significantly higher tangential and normal forces, torques and specific energy (p<0.05) but lower cutting speeds than occlusal surfaces (p<0.05). Increasing material removal rate for high cutting efficiencies using coarse burs yielded remarkable rises in cutting forces and torque (p<0.05) but significant reductions in cutting speed and specific cutting energy (p<0.05). In particular, great variations in cutting forces, torques and specific energy were observed at the specific material removal rate of 3mm3/min/mm using coarse burs, indicating the cutting limit. This work provides fundamental data and the scientific understanding of the enamel machinability for clinical dental practice. © 2014 Elsevier Ltd.

Wang Y.,Tianjin Medical University
Zhonghua nan ke xue = National journal of andrology | Year: 2013

To explore the diagnosis and treatment of xanthogranulomatous prostatitis. A 75-year-old man presented with a 3-month history of difficult urination and frequent micturition, which was exacerbated for 2 days. Digital rectal examination indicated an enlarged prostate size of II degrees with hard texture but no tenderness. Serum total PSA was 172.5 microg/L. TRUS revealed 200 ml of post-micturition residual urine, thickened bladder wall, prostate size of 4.3 cm x 3.8 cm x 5.0 cm and no isochrones. MRI showed an enlarged prostate gland, with marked enlargement of the central zones and low-signal intensity of the peripheral gland, part of the prostate gland protruding to the bladder with no clear dividing line. It was diagnosed as prostate cancer initially, and confirmed by needle biopsy. Histopathological examination revealed large numbers of "foamy macrophages" in the lesion, with a few multinucleated giant cells, leukocytes, mononuclear, plasmocytes and fibroplasia. Immunohistochemistry showed CD68 (+) and PSA (-). The patient was treated with oral Tamsulosin and glucocorticoid and by temporary catheterization, and followed up for 20 months. Urination symptoms began to alleviate and serum PSA to decrease at 4 months. The PSA level was 9.2 microg/L at 13 months and 3.6 microg/L at 17 months. Xanthogranulomatous prostatitis is a rare clinically, which can be confirmed by histopathological examination. It is treated mainly by supportive therapy and, for the cases with severe lower urinary tract obstruction, TURP can be employed. Follow-up must be performed by possible examination of PSA and necessary needle biopsy of the prostate.

Objective To investigate the relationship between structural abnormalities with semi-quantitative score of CT and changes of oxygenation function in patients with post primary tuberculosis. Methods 110 in-patients with post primary tuberculosis in Haihe clinical college of Tianjin medical university from January 2014 to August 2014 were enrolled in this study, all patients underwent CT and blood gas analysis. All lesions in lung as a whole and different CT signs of lesions were evaluated by retrospective semi-quantitative score respectively, total scores obtained by adding the scores of different lesions. The correlation between these scores and the results of blood gas analysis were evaluated. CT scores were compared between group 1 (PaO2/FiO2 < 300 mmHg) and group 2 (PaO2/FiO2 ≥300 mmHg) of patients. Results Overall score of lung lesions and total scores which obtained by adding the score of different signs in patients showed correlation with PaO2/FiO,. and the method of overall score of lung lesions was easy to do. Scores of nodules and tree-in-bud pattern, consolidation, bronchial lesions, cavity showed correlation between PaO2/FiO2. There was no correlation between score of ground-glass opacity and PaO2/FiO2. Nodules and tree-in-bud pattern were more common in post primary tuberculosis, 87.3% (96/110) and 70% (77/110) respectively. Lobular consolidation was dominant in consolidation of patients, 83.6% (92/110). Bronchial wall thickening and bronchiectasis had higher incidence in larger airways, 87.3% (96/110) and 75. 5% (83/110) respectively. Cavities were given priority to with thin walled, 53.6% (59/110). Overall score of lung lesions and scores of bronchial lesions, consolidation, cavity in groups 1 were significantly higher than group 2. Conclusions Semi-quantitative score of CT can better quantify structural abnormalities of the lung, sensitively reflect changes of oxygenation, and bronchial lesions play an important role in the process of post primary tuberculosis.

BACKGROUND:: Dysphagia is a common side effect of anticancer treatments in patients with head and neck cancer (HNC) and can worsen patients’ quality of life. A well-established measure is essential to evaluate dysphagia in HNC patients. OBJECTIVES:: The aim of this study is to determine the psychometric properties of the Chinese version of the M.D. Anderson Dysphagia Inventory (MDADI-C) for HNC patients. METHODS:: A total of 220 subjects were included in the study. Reliability was examined by internal consistency (Cronbach’s α) and test-retest reliability (intraclass correlation coefficient). Validity was evaluated with Spearman correlations (r). RESULTS:: The Cronbach’s α and intraclass correlation coefficient of the MDADI-C were .923 and 0.942, respectively. The criterion validity of the MDADI-C was 0.777. The Spearman correlation coefficients of the MDADI-C with the European Organization for Research Into the Treatment of Cancer Quality of Life Questionnaire for Head and Neck Cancer (r = −0.851), Hospital Anxiety and Depression Scale (r = −0.424), radiotherapy dose (r = −0.553), and treatment regimens (r = −0.407) demonstrated good construct validity (all P < .01). CONCLUSIONS:: The MDADI-C demonstrated good psychometric properties and would be a valuable tool for clinicians to screen dysphagia rapidly and evaluate its impact on the quality of life of HNC patients. IMPLICATIONS FOR PRACTICE:: The MDADI-C could be used to document and monitor the dysphagia level of HNC patients for clinicians, nurses, and researchers. This validated questionnaire will help nurses and doctors to improve dysphagia management in HNC patients and will allow researchers to compare the study results across different countries. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved

Hao Y.,Sichuan University | Gu J.,CAS Shanghai Institute of Materia Medica | Guo Y.,Neijiang Normal University | Zhang M.,Tianjin Medical University | And 2 more authors.
Physical Chemistry Chemical Physics | Year: 2014

Using the CCSD(T) method with relativistic correlation consistent basis sets up to cc-pVQZ-PP, the entrance complex, transition state, and exit complex for the endothermic reaction I + H2O → HI + OH have been studied. The vibrational frequencies and the zero-point vibrational energies of the five stationary points for the title reaction are reported and compared with the limited available experimental results. Opposite to the valence isoelectronic F + H2O system, but similar to the Cl + H2O and Br + H2O reactions, the I + H2O reaction is endothermic, in this case by 46 kcal mol-1. After the zero-point vibrational energy and spin-orbit coupling corrections, the endothermic reaction energy is predicted to be 48 kcal mol-1, which agrees well with experimental values. For the reverse reaction HI + OH → I + H2O the transition state lies below the reactants, consistent with the experimental negative temperature dependence for the rate constants. © 2014 the Owner Societies.

Sun L.,Nankai University | Zhang X.,Nankai University | Zheng C.,Nankai University | Wu Z.,Tianjin Medical University | Li C.,Nankai University
Journal of Physical Chemistry B | Year: 2013

This study prepares a kind of core-shell hybrid nanoparticles, which is worm-like, pH gated, and glucose-sensitive. It has a mesoporous silica nanoparticle (MSN) core and polymer shell (cross-linked and non-cross-linked), bearing 3-acrylamidophenylboronic acid (AAPBA) and N-isopropylacrylamide (NIPAM) as sensor moieties. The shell of the nanoparticles has presented a distinct transition from swollen state to collapsed state as the temperature increases, which offers easy access to drug loading. Here, insulin is applied as a model drug and the behaviors of its loading/release are investigated. Insulin loading is up to 15% via mesoporous silica core. In vitro experiment shows that the cumulative release of insulin is dependent on glucose concentration, and the glucose sensitivity could be adjusted simply by different pH values. Simultaneously, compared with the non-cross-linked shell, the cross-linked shell, using dextran-maleic acid (Dex-Ma) as a macromolecule cross-link, enables insulin to release more persistently. Also, cell viability assay indicates that these nanoparticles have good biocompatibility. Consequently, the novel, pH gated, glucose-sensitive core-shell nanoparticles may have potential applications as a vehicle of self-regulated insulin delivery system. © 2013 American Chemical Society.

Thorn D.A.,State University of New York at Buffalo | Jing L.,State University of New York at Buffalo | Jing L.,Tianjin Medical University | Qiu Y.,State University of New York at Buffalo | And 5 more authors.
Neuropsychopharmacology | Year: 2014

Animal knockout studies suggest that trace amine-associated receptor (TAAR) 1 is involved in behavioral effects of psychostimulants such as cocaine. Recently, several highly selective TAAR 1 agonists have been discovered. However, little is known of the impact of TAAR 1 agonists on abuse-related effects of cocaine. Here, we report the effects of a TAAR 1 agonist RO5263397 on several abuse-related behavioral effects of cocaine in rats. RO5263397 was evaluated for its effects on cocaine-induced behavioral sensitization, conditioned place preference (CPP), cue- and cocaine prime-induced reinstatement of cocaine-seeking behavior, and cocaine self-administration using behavioral economic analysis. RO5263397 reduced the expression of cocaine behavioral sensitization, cue- and cocaine prime-induced reinstatement of cocaine seeking, and expression but not development of cocaine CPP. Behavioral economic analysis showed that RO5263397 increased the elasticity of the cocaine demand curve, but did not change cocaine consumption at minimal prices. Taken together, this is the first systematic assessment of a TAAR 1 agonist on a range of behavioral effects of cocaine, showing that RO5263397 was efficacious in reducing cocaine-mediated behaviors. Collectively, these data uncover essential neuromodulatory roles of TAAR 1 on cocaine abuse, and suggest that TAAR 1 may represent a novel drug target for the treatment of cocaine addiction. © 2014 American College of Neuropsychopharmacology.

Singh B.N.,Banaras Hindu University | Zhang G.,Tianjin Medical University | Hwa Y.L.,Mayo Medical School | Li J.,Mercer University | And 2 more authors.
Expert Review of Anticancer Therapy | Year: 2010

Acetylation and deacetylation are counteracting, post-translational modifications that affect a large number of histone and nonhistone proteins. The significance of histone acetylation in the modification of chromatin structure and dynamics, and thereby gene transcription regulation, has been well recognized. A steadily growing number of nonhistone proteins have been identified as acetylation targets and reversible lysine acetylation in these proteins plays an important role(s) in the regulation of mRNA stability, protein localization and degradation, and protein-protein and protein-DNA interactions. The recruitment of histone acetyltransferases (HATs) and histone deacetylases (HDACs) to the transcriptional machinery is a key element in the dynamic regulation of genes controlling cellular proliferation, differentiation and apoptosis. Many nonhistone proteins targeted by acetylation are the products of oncogenes or tumor-suppressor genes and are directly involved in tumorigenesis, tumor progression and metastasis. Aberrant activity of HDACs has been documented in several types of cancers and HDAC inhibitors (HDACi) have been employed for therapeutic purposes. Here we review the published literature in this field and provide updated information on the regulation and function of nonhistone protein acetylation. While concentrating on the molecular mechanism and pathways involved in the addition and removal of the acetyl moiety, therapeutic modalities of HDACi are also discussed. © 2010 Expert Reviews Ltd.

Shumin X.,Central South University | Woo S.M.-L.,Harvard University | Lei Z.,Tianjin Medical University
Patient Preference and Adherence | Year: 2014

In recent decades, the demand for organ transplantation has risen rapidly worldwide, due to an increased incidence of vital organ failure. However, the scarcity of organs appropriate for transplantation has led to an organ shortage crisis. This article retrospectively reviews strategies to change negative public attitudes toward organ donation in the People's Republic of China. We strongly believe that efforts to publicize knowledge of organ donation, promote family discussions, train medical staff and students, establish incentive systems, and implement regulatory oversight may combat unfavorable Chinese public opinion toward organ donation and transplantation, thus potentially increasing the organ donation rate in the People's Republic of China. © 2014 Shumin et al.

Ma X.G.,Tianjin Medical University
Zhonghua fu chan ke za zhi | Year: 2012

To explore the clinical pathological characteristics of Lynch syndrome associated ovarian cancer. Totally 260 cases ovarian cancer patients were admitted to Tianjin Medical University General Hospital during Jan. 2004 and Jan. 2011, among which 10 patients (LS group) belonged to Lynch syndrome associated ovarian cancer according to Amsterdam II criteria. One hundred ovarian cancer patients without any family cancer history were enrolled randomizely as control group (sporadic group). Lynch syndrome associated ovarian cancer accounted for 3.8% (10/260), the incidence rate of ovarian cancer for female family members of Lynch syndrome was 8.7% (10/115). Mean age at time of diagnosis in LS group was (46 ± 7) years, significantly earlier than that in sporadic group [(56 ± 11) years, P < 0.05]. There was no statistical difference between two groups in histological type or International Federation of Gynecology and Obstetrics (FIGO) stage (P > 0.05). Most of the tissue differentiation in LS group were well or moderate differentiated, there was statistical difference between the two groups (9/10 vs. 55%, P < 0.05). The 3-year and 5-year survival rate in LS group were 87.5% and 52.5% respectively, compared with 55.4%and 22.7% in sporadic group (all P < 0.05). Compared with sporadic ovarian cancer, Lynch syndrome associated ovarian cancer is more likely present as the clinical pathological characteristics of early age of onset, serous adenocarcinoma, lower grade and better prognosis.

Hao C.,Tianjin Medical University
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2012

The purpose of this study was to investigate the effect of Raf kinase inhibitor protein (RKIP) on the growth, proliferation, invasion and metastasis of triple-negative breast cancer (TNBC) cells to provide experimental evidence for developing future therapies against human TNBC. The pcDNA3.1-RKIP eukaryotic expression vector was constructed and transfected into the TNBC cell line MDA-MB-231. The alterations of the biological characteristics of RKIP-transfected MDA-MB-231 cells were analyzed using the following approaches: a growth curve, a 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay, bromodeoxyuridine (BrdU) staining and a cell migration assay. The effects of the RKIP gene on MMP-1 and MMP-2 expression were also examined. The pcDNA3.1 empty vector-transfected and mock-transfected MDA-MB-231 cells were used as control groups. Compared with the empty vector-transfected and mock-transfected cells, the cell growth of RKIP-transfected MDA-MB-231 cells was significantly reduced. The empty vector-transfected group was not significantly different compared with the mock-transfected MDA-MB-231 cells. The results of the MTT and BrdU assays demonstrated that the proliferation of pcDNA3.1-RKIP-transfected cells was significantly reduced compared to the control cells (P < 0.05). The result of the cell migration assay suggested that the cross-membrane migration rate of the pcDNA3.1-RKIP-transfected cells was significantly lower than that of the control MDA-MB-231 cells (P < 0.05). We also demonstrated that RKIP may inhibit MMP-1 and MMP-2 expression in MDA-MB-231 cells. The RKIP gene may play a role in inhibiting cellular proliferation. The RKIP gene may also have some inhibitory effects on the invasiveness and metastatic capability of human TNBC cells.

Xing J.,Tianjin Medical University
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology | Year: 2011

To evaluate the efficacy of entecavir (ETV) 1.0 mg/d or ETV plus adefovir dipivoxil (ADV) in adults with chronic hepatitis B virus (HBV) infection who had previously resisted lamivudine (LAM) and failed with rescue treatment of LAM + ADV. 40 patients were enrolled. 14 patients were treated with ETV 1.0 mg/d monotherapy while 26 patients were treated with ETV 1.0 mg/d + ADV 10 mg/d. The HBV DNA level, liver function, HBV serology and renal function were observed. There was no statistically significant difference with baseline situation between group ETV 1.0 mg and group ETV + ADV. HBV DNA level in group ETV 1.0 mg was (5.768 ± 0.709) log10 copies/ml on baseline, and it declined to (4.712 ± 0.846) log10 copies/ml, (3.914 ± 0.996) log10 copies/ml, (3.702 ± 0.934) log10 copies/ml, (3.879 ± 0.913) log10 copies/ml and (3.855 ± 1.070) log10 copies/ml at 4, 8, 12, 24 and 48 weeks. HBV DNA level in group ETV + ADV was (5.703 ± 0.845) log10 copies/ml on baseline, and it declined to (4.476 ± 0.905) log10 copies/ml, (3.590 ± 0.884) log10 copies/ml, (2.987 ± 0.673) log10 copies/ml and (2.933 ± 0.535) log10 copies/ml at 4, 8, 12 and 24 weeks. At 24 weeks, there were 28.6% patients achieved HBV DNA < 500 copies/ml in group ETV 1.0 mg, but there were 80.8% patients in group ETV + ADV achieved this level. Statistically significant difference existed between (x(2) = 8.469, P = 0.004 ). At 48 weeks, there were still 4 patients achieved HBV DNA < 500 copies/ml in group ETV 1.0 mg, but patients in group ETV + ADV all achieved it. At 24 weeks, ALT levels of 42.9% patients in group ETV 1.0 mg were back to normal, but there were 92.3% patients' ALT levels back to normal in group ETV + ADV. There was statistically significant difference (x(2) = 9.337, P = 0.002). At 48 weeks, ALT levels of 57.1% patients in group ETV 1.0 mg were back to normal, but all patients' ALT levels were back to normal in group ETV + ADV. At 48 weeks, there was 1 patient with HBeAg seroconversion in group ETV 1.0 mg while there were 4 patients in group ETV + ADV. As rescue treatment for patients with chronic hepatitis B who had previously resisted LAM and failed with treatment of LAM + ADV, ETV + ADV was more efficient than ETV 1.0 mg monotherapy, and it can achieve better virological and biochemical response.

Fan Y.,Tianjin Medical University
Journal of Exposure Science and Environmental Epidemiology | Year: 2016

Arsenic and prior lung diseases have been shown to increase lung cancer risk; however, little is known about their joint effects. The aim of our study was to analyze the joint effects of inhaled arsenic and prior lung diseases on lung cancer risk within a occupational cohort. The interactions of prior lung diseases and inhaled arsenic were analyzed based on multiplicative and additive scales in the Cox proportional hazards model. Compared with low arsenic exposure and no history of asthma, the hazard ratios (HRs) of high arsenic exposure with asthma, high arsenic exposure without asthma and low arsenic exposure with asthma were 2.61 (95% CI: 1.71–4.00), 2.60 (95% CI: 1.93–3.51) and 2.49 (95% CI: 1.53–4.06), respectively. Based on the multiplicative scale in the Cox proportional hazards model, the HR of the interaction of asthma and arsenic on lung cancer risk was 0.45 (95% CI: 0.25–0.80). Based on the additive scale, the relative excess risk due to interaction between asthma and arsenic was −1.41 (95% CI: −2.81 to −0.02). Our study provides strong evidence that arsenic exposure is associated with lung cancer risk. A significant negative interaction between asthma and arsenic on lung cancer risk is observed.Journal of Exposure Science and Environmental Epidemiology advance online publication, 13 April 2016; doi:10.1038/jes.2016.22. © 2016 Nature America, Inc.

Objective: To evaluate the efficacy of nimotuzumab combined with palitaxel liposome and carboplatin (LP) regimen for treatment of advanced non-small cell lung cancer (NSCLC), and to observe the changes of tumor markers and toxicities in the treatment. Methods: Forty-one patients with advanced NSCLC were randomly divided into 2 groups: 21 patients in the observation group were treated with nimotuzumab (200 mg per week for 6 weeks), palitaxel liposome 160 mg/m 2 and carboplatin (AUC = 6). 20 patients in the control group were given LP regimen. Each group completed two cycles of chemotherapy. The level of tumor markers (CEA, CYFR21-1 and NSE) and toxicities were checked at one week before and after the treatment. Thoracic CT examinations were taken before treatment and at the fourth week and eighth week after treatment. Results: In the observation group, there were 2 cases of CR, 7 cases of PR, 9 cases of SD and 3 cases of PD. The objective response rate (RR) was 42.9% in the observation group. In the control group, there were 1 case of CR, 6 cases of PR, 8 cases of SD and 5 cases of PD, with a RR of 35.0% in this group. There was no significant difference in the RR between the two groups (P = 0.751). The time to progression (TTP) was 6.9 months in the observation group and 5.7 months in the control group, with a significant difference (P = 0.027). The levels of NSE decreased significantly in both groups and showed a significant difference (P = 0.039). The levels of CEA and CYFRA21 in both groups were decreased after treatment, but did not show a significant difference before and after treatment, respectively. Except 3 cases had I-II skin toxicities on the faces in the observation group, there was no significant difference in toxicities between the two groups. Conclusion: Nimotuzmab combined with LP regimen shows a synergistic effect, can increase the efficacy and prolong TTP in advanced NSCLC patients. The toxicities are mild and tolerable.

Li Y.,Tianjin Medical University
Physical Chemistry Chemical Physics | Year: 2014

The recruitment dynamics of lipids in the biomembrane is believed to play an important role in a variety of cellular processes. In this work, we investigate the nanoparticle-induced recruitment dynamics of lipids in the heterogeneous phospholipid bilayers of distearoyl-phosphatidylcholine (DSPC) and dioleoyl-phosphatidylglycerol (DOPG) via coarse-grained molecular dynamics simulations. Three dynamic modes of individual charged DOPG lipid molecules have been taken into account in the recruitment process: lateral diffusion, protrusions, and flip-flops. Based on analysis of the mobility pattern of lipids, structural variations in the membrane as well as activation energy of the structure of lipid eyelids characterized by the potential of mean force, we have concluded that the electrostatic attraction of nanoparticles plays a crucial role in the recruitment process of lipids in phospholipid bilayers. These studies are consistent with experimental observations and to some extent give insight into the origin of some cellular processes such as signaling, formation of lipid rafts, and endocytosis. This journal is © the Partner Organisations 2014.

Feng Q.,Tianjin Medical University | Feng Q.,Weifang Medical University | Ma Z.,Weifang Medical University | Wu J.,Dalian University | Fang W.,Weifang Medical University
European Radiology | Year: 2015

Results: ADC values decreased with increased stages. ADC differences in renal parenchyma at different disease stages were found, with the exception of the control group compared with stage 1 patients; similar results were obtained for FA. ADC values in the cortex and medulla in stage 1-3 patients were both statistically different, similar to the FA values. A significant negative correlation was found between the percentage of glomerulosclerosis and FA in the renal cortex (r = -0.74), similar to the degree of tubulointerstitial fibrosis with FA in the medulla (r = -0.76).Conclusions: ADC and FA values are correlated with the degree of renal impairment, the percentage of glomerulosclerosis, and area of interstitial fibrosis.Key Points: • DTI can be used to assess renal function impairment in patients with chronic glomerulonephritis.• ADC and FA values were correlated with tubulointerstitial fibrosis and glomerulosclerosis.• Identification of renal impairment is helpful for timely treatment.• DTI can be used for non-invasive assessment of renal pathology.Materials and methods: Seventy-five patients and 20 healthy volunteers were enrolled in this study. Renal function and kidney biopsies were evaluated. For DTI, a respiratory-triggered coronal EPI sequence was performed (TR, 1400 ms; TE, 76 ms; diffusion direction, 6; NEX, 4; b values, 0 and 600 s/mm2; slices thickness, 6 mm, with no intersection gap). Renal ADC and FA values were calculated and compared between the groups. Correlations between ADC/FA and histopathology were evaluated.Objectives: To investigate whether DTI allows assessment of renal impairment and pathology in patients with chronic glomerulonephritis. © 2014, European Society of Radiology.

Sun A.,Tianjin Medical University | Liu R.,Tianjin Union Medicine Center | Sun G.,Tianjin Junliangcheng Hospital
Current Medical Research and Opinion | Year: 2014

Objective: An increasing number of studies show that exogenous insulin therapy may promote colorectal carcinogenesis. However, the results of the association between insulin therapy and risk of colorectal cancer (CRC) among type 2 diabetes patients are inconsistent. The purpose of our study is to examine the effect of insulin therapy on CRC risk among patients with type 2 diabetes in an updated meta-analysis. Research design and methods: Medline and Embase were searched for the reference lists of pertinent articles published from January 1970 to April 2013. Two investigators independently extracted the data and reached consensus on the inclusion and exclusion criteria. Pooled relative risks and 95% confidence intervals were calculated with a random-effects model. Results: Analysis of six studies, including 374,950 participants, showed that compared with non-insulin or metformin treatment, insulin treatment was associated with an increase of 37% in the risk of colorectal neoplasm among patients with type 2 diabetes, with moderate heterogeneity (I2= 40%). The sensitivity analysis showed that exclusion of one small case-control study had no appreciable changes on the pooled results. Subgroup analyses suggested that there were significant positive associations between insulin therapy and risk of CRC in some subgroups, rather than all subgroups. Conclusions: Our meta-analysis supports a relationship between insulin therapy and increased risk of CRC in patients with type 2 diabetes. Because of bias and confounding of included studies, caution is needed when interpreting our results. Further investigations are needed. © 2014 Informa UK Ltd.

Bizet A.A.,McGill University | Tran-Khanh N.,Ecole Polytechnique de Montreal | Saksena A.,McGill University | Liu K.,McGill University | And 3 more authors.
Journal of Cellular Biochemistry | Year: 2012

Transforming growth factor-β (TGF-β) is a multifunctional cytokine that regulates a wide variety of cellular processes including proliferation, differentiation, and extracellular matrix deposition. Dysregulation of TGF-β signaling is associated with several diseases such as cancer and tissue fibrosis. TGF-β signals through two transmembrane proteins known as the type I (TGFBR1) and type II (TGFBR2) receptors. The levels of these receptors at the cell surface are tightly regulated by several mechanisms, including degradation following recruitment of the E3 ubiquitin ligase SMAD ubiquitination regulatory factor (Smurf) 2 by SMAD7. In addition, TGF-β co-receptors can modulate TGF-β signaling receptor activity in a cell-specific manner. We have previously identified a novel TGF-β co-receptor, CD109, a glycosyl phosphatidylinositol (GPI)-anchored protein that negatively regulates TGF-β signaling. Despite CD109's potential relevance as a regulator of TGF-β action in vivo, the mechanisms by which CD109 regulates TGF-β signaling are still incompletely understood. Previously, we have shown that CD109 downregulates TGF-β signaling by promoting TGF-β receptor localization into the lipid raft/caveolae compartment and by enhancing TGF-β receptor degradation. Here, we demonstrate that CD109 enhances SMAD7/Smurf2-mediated degradation of TGFBR1 in a ligand-dependent manner. Moreover, we show that CD109 regulates the localization and the association of SMAD7/Smurf2 with TGFBR1. Finally, we demonstrate that CD109's inhibitory effect on TGF-β signaling and responses require SMAD7 expression and Smurf2 ubiquitin ligase activity. Taken together, these results suggest that CD109 is an important regulator of SMAD7/Smurf2-mediated degradation of TGFBR1. Copyright © 2011 Wiley Periodicals, Inc.

Wang Y.-Q.,Tianjin Medical University
World Chinese Journal of Digestology | Year: 2015

AIM: To apply preventive comprehensive intestinal irritation in mechanically ventilated critically ill patients, and observe its impact on patients’ gastrointestinal function. METHODS: One hundred mechanically ventilated critical patients were randomly divided into an intervention group and a control group, with 50 patients in each group. The control group underwent conventional treatment, and the intervention group was additionally given comprehensive intestinal irritation on the basis of convent ional treatment. The incidence of gastrointestinal dysfunction, gastrin levels and intra-abdominal pressure were compared between the two groups. Gastrointestinal dysfunction was classified using the acute gastric injury classification system. RESULTS: The incidence of gastrointestinal dysfunction in the intervention group was 32.0% (16/50), significantly lower than that in the control group [54.0% (27/50); χ2 = 4.937, P = 0.026]. The rates of diarrhea, bloating, toxic intestinal paralysis and stress ulcer bleeding in the intervention group were significantly lower than those in the control group (P < 0.05). Gastrin levels and intra-abdominal pressure in gastrointestinal dysfunction patients of the intervention group were significantly lower than those of the control group (P < 0.05). The rate of grade III acute gastric injury in the intervention group was 6.25% (1/16), significantly lower than that in the control group [33.33% (9/27); P < 0.05]. CONCLUSION: Comprehensive preventive intestinal irritation applied in mechanically ventilated critically ill patients can effectivelyreduce the incidence of gastrointestinal dysfunction and the extent of gastrointestinal injury. © 2015 Baishideng Publishing Group Inc. All rights reserved.

Cai C.,Tianjin Childrens Hospital | Shi O.,Tianjin Medical University
Frontiers of Medicine in China | Year: 2014

Neural tube defects (NTDs) are a group of birth anomalies having a profound physical, emotional, and financial effects on families and communities. Their etiology is complex, involving environmental and genetic factors that interact to modulate the incidence and severity of the developing phenotype. The planar cell polarity (PCP) pathway controls the process of convergent extension (CE) during gastrulation and neural tube closure and has been implicated in the pathogenesis of NTDs in animal models and human cohorts. This review summarizes the cumulative results of recent studies on PCP signaling pathway and human NTDs. These results demonstrate that PCP gene alterations contribute to the etiology of human NTDs. © 2014 Higher Education Press and Springer-Verlag Berlin Heidelberg.

Liu Y.,Tianjin Medical University | Liu Y.,College of Logistics | Wei L.-Q.,College of Logistics | Li G.-Q.,College of Logistics | And 3 more authors.
Critical Care Medicine | Year: 2016

Objectives: 1) To evaluate the ability of pulse pressure variation adjusted by respiratory changes in pleural pressure to predict fluid responsiveness compared with pulse pressure variation alone. 2) To identify factors explaining the poor performance of pulse pressure variation in acute respiratory distress syndrome. Design: Prospective study. Setting: Forty-bed university hospital general ICU. Patients: Ninety-six mechanically ventilated acute respiratory distress syndrome patients requiring fluid challenge. Interventions: Fluid challenge, 500 mL saline over 20 minutes. Measurements and Main Results: Before fluid challenge, esophageal pressure was measured at the end-inspiratory and end-expiratory occlusions. Change in pleural pressure was calculated as the difference between esophageal pressure measured at end-inspiratory and end-expiratory occlusions. Hemodynamic measurements were obtained before and after the fluid challenge. Patients were ventilated with tidal volume 7.0 ± 0.8 mL/kg predicted body weight. The fluids increased cardiac output by greater than 15% in 52 patients (responders). Adjusting pulse pressure variation for changes in pleural pressure (area under the receiver operating characteristic curve, 0.94 [0.88-0.98]) and the ratio of chest wall elastance to total respiratory system elastance (area under the receiver operating characteristic curve, 0.93 [0.88-0.98]) predicted fluid responsiveness better than pulse pressure variation (area under the receiver operating characteristic curve, 0.78 [0.69-0.86]; all p < 0.01). The gray zone approach identified a range of pulse pressure variation/changes in pleural pressure values (1.94-2.1) in 3.1% of patients for whom fluid responsiveness could not be predicted reliably. On logistic regression analysis, two independent factors affected the correct classification of fluid responsiveness at a 12% pulse pressure variation cutoff: tidal volume (adjusted odds ratio 1.57/50 mL; 95% CI, 1.05-2.34; p = 0.027) and chest wall elastance/respiratory system elastance (adjusted odds ratio, 2.035/0.1 unit; 95% CI, 1.36-3.06; p = 0.001). In patients with chest wall elastance/respiratory system elastance above the median (0.28), pulse pressure variation area under the receiver operating characteristic curve was 0.94 (95% CI, 0.84-0.99) compared with 0.76 (95% CI, 0.61-0.87) otherwise (p = 0.02). Conclusions: In acute respiratory distress syndrome patients, pulse pressure variation adjusted by changes in pleural pressure is a reliable fluid responsiveness predictor despite the low tidal volume (< 8 mL/kg). The poor predictive ability of pulse pressure variation in acute respiratory distress syndrome patients is more related to low chest wall elastance/respiratory system elastance ratios than to a low tidal volume. © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Chen Y.,Zhejiang University | Deng Y.,Tianjin Medical University | Zhang B.,Zhejiang University | Gong C.-X.,New York State Institute for Basic Research in Developmental Disabilities
Neuroscience Bulletin | Year: 2014

Contrary to the previous belief that insulin does not act in the brain, studies in the last three decades have demonstrated important roles of insulin and insulin signal transduction in various functions of the central nervous system. Deregulated brain insulin signaling and its role in molecular pathogenesis have recently been reported in Alzheimer's disease (AD). In this article, we review the roles of brain insulin signaling in memory and cognition, the metabolism of amyloid β precursor protein, and tau phosphorylation. We further discuss deficiencies of brain insulin signaling and glucose metabolism, their roles in the development of AD, and recent studies that target the brain insulin signaling pathway for the treatment of AD. It is clear now that deregulation of brain insulin signaling plays an important role in the development of sporadic AD. The brain insulin signaling pathway also offers a promising therapeutic target for treating AD and probably other neurodegenerative disorders. © 2014 Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag.

Occult breast carcinoma presenting axillary metastases is uncommon and accounts for less than 1% of newly diagnosed breast carcinoma. However, it continues to be a challenging diagnostic and therapeutic problem. In this study, we analyzed retrospectively on 51 cases of occult breast cancer from 1990 to 2003 in our hospital. All these patients had a palpable axillary nodule, no dominant breast mass, and no abnormal mammograms and breast ultrasonograph. Histological examination of axillary mass revealed metastasis from breast. The positive rate of estrogen receptor, progesterone receptor and the monoclonal antibody M4G3 against human breast cancer showed 62.7%, 66.7%, and 93.1% positive respectively. Among 51 cases, 38 cases received mastectomy whereas 13 cases had no local treatment of the breast. The primary tumors were detected in 28 of 38 cases having mastectomy by pathology. Seventy-seven percent of patients who had no local treatment of the breast had a tumor recurrence, compared with 26% who had a mastectomy. The mean disease-free survival was 23 months in patients who had no local treatment of the breast, compared with 76 months in patients who had mastectomy. Eight of the 13 patients who had no treatment with breast died whereas seven of the 38 who had local treatment died, with a mean follow-up of 73 months. It was found that patients having mastectomy had a better disease-free survival (p < 0.001) and overall survival (p < 0.001) compared with those having no local treatment of the breast. Once the diagnosis of occult breast carcinoma is clarified, an axillary dissection and the local treatment of breast should be carried out. © 2009 Wiley Periodicals, Inc., 1075-122X/09.

Min K.A.,University of Michigan | Shin M.C.,University of Michigan | Yu F.,Wuhan Institute of Technology | Yang M.,Wuhan Institute of Technology | And 4 more authors.
ACS Nano | Year: 2013

Understanding how a magnetic field affects the interaction of magnetic nanoparticles (MNPs) with cells is fundamental to any potential downstream applications of MNPs as gene and drug delivery vehicles. Here, we present a quantitative analysis of how a pulsed magnetic field influences the manner in which MNPs interact with and penetrate across a cell monolayer. Relative to a constant magnetic field, the rate of MNP uptake and transport across cell monolayers was enhanced by a pulsed magnetic field. MNP transport across cells was significantly inhibited at low temperature under both constant and pulsed magnetic field conditions, consistent with an active mechanism (i.e., endocytosis) mediating MNP transport. Microscopic observations and biochemical analysis indicated that, in a constant magnetic field, transport of MNPs across the cells was inhibited due to the formation of large (>2 μm) magnetically induced MNP aggregates, which exceeded the size of endocytic vesicles. Thus, a pulsed magnetic field enhances the cellular uptake and transport of MNPs across cell barriers relative to a constant magnetic field by promoting accumulation while minimizing magnetically induced MNP aggregation at the cell surface. © 2013 American Chemical Society.

BACKGROUND:: Hyperalgesia is one of the negative consequences following intraoperative analgesia with remifentanil. Peroxynitrite is a critical determinant in nociceptive process. Peroxynitrite inactivates iron-sulfur cluster that results in mitochondrial dysfunction and the release of iron, leading to mitochondrial iron accumulation. Iron accumulation mediated by divalent metal transporter 1 (DMT1) plays a key role in N-methyl-D-aspartate neurotoxicity. This study aims to determine whether peroxynitrite contributes to remifentanil-induced postoperative hyperalgesia via DMT1-mediated iron accumulation.METHODS:: Behavior testing was performed in rat model at different time points. Three-nitrotyrosine, nitrated manganese superoxide dismutase, and DMT1 with/without iron-responsive element [DMT1(+)IRE and DMT1(-)IRE] in spinal cord were detected by Western blot and immunohistochemistry. Spinal iron concentration was measured using the Perl stain and atomic absorption spectrophotometer. Hydrogen-rich saline imparting selectivity for peroxynitrite decomposition and iron chelator was applied in mechanistic study on the roles of peroxynitrite and iron, as well as the prevention of hyperalgesia.RESULTS:: Remifentanil induced thermal and mechanical hyperalgesia at postoperative 48 h. Compared with control, there were higher levels of 3-nitrotyrosine (mean ± SD, hyperalgesia vs. control, 1.22 ± 0.18 vs. 0.25 ± 0.05, n = 4), nitrated manganese superoxide dismutase (1.01 ± 0.1 vs. 0.19 ± 0.03, n = 4), DMT1(-)IRE (1.42 ± 0.19 vs. 0.33 ± 0.06, n = 4), and iron concentration (12.87 ± 1.14 vs. 5.26 ± 0.61 μg/g, n = 6) in remifentanil-induced postoperative hyperalgesia, while DMT1(+)IRE was unaffected. Eliminating peroxynitrite with hydrogen-rich saline protected against hyperalgesia and attenuated DMT1(-)IRE overexpression and iron accumulation. Iron chelator prevented hyperalgesia in a dose-dependent manner.CONCLUSIONS:: Our study identifies that spinal peroxynitrite activates DMT1(-)IRE, leading to abnormal iron accumulation in remifentanil-induced postoperative hyperalgesia, while providing the rationale for the development of molecular hydrogen and “iron-targeted” therapies. © 2014 American Society of Anesthesiologists, Inc.

Liu L.,University of Georgia | Wu S.,Tianjin Medical University | Yu L.,Georgia Southern University
Journal of Systematics and Evolution | Year: 2015

Genome-scale sequence data have become increasingly available in the phylogenetic studies for understanding the evolutionary histories of species. However, it is challenging to develop probabilistic models to account for heterogeneity of phylogenomic data. The multispecies coalescent model describes gene trees as independent random variables generated from a coalescence process occurring along the lineages of the species tree. Since the multispecies coalescent model allows gene trees to vary across genes, coalescent-based methods have been popularly used to account for heterogeneous gene trees in phylogenomic data analysis. In this paper, we summarize and evaluate the performance of coalescent-based methods for estimating species trees from genome-scale sequence data. We investigate the effects of deep coalescence and mutation on the performance of species tree estimation methods. We found that the coalescent-based methods perform well in estimating species trees for a large number of genes, regardless of the degree of deep coalescence and mutation. The performance of the coalescent methods is negatively correlated with the lengths of internal branches of the species tree. © 2015 Institute of Botany, Chinese Academy of Sciences.

Liang Y.X.,Tianjin Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2013

To elucidate the necessity of No.14v lymph node dissection in D2 lymphadenectomy for advanced gastric cancer. Clinicopathological data of 131 cases of advanced gastric cancer receiving D2 or D2+ plus No.14v lymph node dissection were reviewed retrospectively. Clinicopathological factors associated with No.14v lymph node metastasis were analyzed and prognostic value of No.14v lymph node metastasis was evaluated. Of the 131 patients, 24 (18.3%) had positive No.14v lymph node. The incidence of 14v metastasis was associated with tumor location, tumor size, depth of invasion, N staging, TNM staging, No.1, No.6, and No.8a lymph nodes metastasis. Tumor location and N staging were independent risk factors for No.14v metastasis (all P<0.05). The 5-year survival rate was 8.3% and 37.8% in patients with and without No.14v metastasis respectively. The difference was statistically significant (P<0.01). Multivariate analysis revealed that metastasis of No.14v was an independent prognostic factor for advanced gastric cancer after D2 lymphadenectomy (P=0.029, RR=1.807, 95%CI:1.064-3.070). For advanced middle and lower gastric cancers, especially those with larger size, serosa invasion and possibility of No.6 lymph node metastasis, it is necessary and feasible to remove the No.14v lymph node.

Cole A.J.,University of Michigan | David A.E.,University of Michigan | David A.E.,Industrial Science and Technology Network Inc. | Wang J.,University of Michigan | And 4 more authors.
Biomaterials | Year: 2011

Magnetic iron oxide nanoparticles (MNPs) have been studied to circumvent the limitations of status-quo brain tumor therapy and can be targeted by applying an external magnetic field to lesions. To address the pharmacokinetic shortcomings of MNPs that can limit targeting efficiency, we recently reported a long-circulating polyethylene glycol modified, cross-linked starch MNP (PEG-MNP) suitable for magnetic targeting. Using a rat model, this work explores the biodistribution patterns of PEG-MNPs in organs of elimination (liver, spleen, lung, and kidney) and shows proof-of-concept that enhanced magnetic brain tumor targeting can be achieved due to the relatively long circulation lifetime of the nanoparticles. Reductions in liver (∼12-fold) and spleen (∼2.5-fold) PEG-MNP concentrations at 1. h compared to parent starch-coated MNPs (D) confirm plasma pharmacokinetics observed previously. While liver concentrations of PEG-MNPs remained considerably lower than those observed for D at 1. h through 60 h, spleen values continue to increase and are markedly higher at later time points - a trend also observed with histology. Limited to no distribution of PEG-MNPs was visualized in lung or kidney throughout the 60. h course evaluated. Enhanced, selective magnetic brain tumor targeting (t = 1 h) of PEG-MNPs (12 mg Fe/kg) was confirmed in 9L-glioma tumors, with up to 1.0% injected dose/g tissue nanoparticle delivery achieved - a 15-fold improvement over targeted D (0.07% injected dose/g tissue). MRI and histological analyses visually confirmed enhanced targeting and also suggest a limited contribution of passive mechanisms to tissue retention of nanoparticles. Our results are exciting and justify both further development of PEG-MNP as a drug delivery platform and concurrent optimization of the magnetic brain tumor targeting strategy utilized. © 2011 Elsevier Ltd.

Tao Q.,Capital Medical University | Li D.,Capital Medical University | Li D.,Tianjin Medical University | Zhang L.,Capital Medical University | Luo S.,Capital Medical University
PLoS ONE | Year: 2012

The purpose of this paper is to report the noninvasive imaging of hepatic tumors without contrast agents. Both normal tissues and tumor tissues can be detected, and tumor tissues in different stages can be classified quantitatively. We implanted BEL-7402 human hepatocellular carcinoma cells into the livers of nude mice and then imaged the livers using X-ray in-line phase-contrast imaging (ILPCI). The projection images' texture feature based on gray level co-occurrence matrix (GLCM) and dual-tree complex wavelet transforms (DTCWT) were extracted to discriminate normal tissues and tumor tissues. Different stages of hepatic tumors were classified using support vector machines (SVM). Images of livers from nude mice sacrificed 6 days after inoculation with cancer cells show diffuse distribution of the tumor tissue, but images of livers from nude mice sacrificed 9, 12, or 15 days after inoculation with cancer cells show necrotic lumps in the tumor tissue. The results of the principal component analysis (PCA) of the texture features based on GLCM of normal regions were positive, but those of tumor regions were negative. The results of PCA of the texture features based on DTCWT of normal regions were greater than those of tumor regions. The values of the texture features in low-frequency coefficient images increased monotonically with the growth of the tumors. Different stages of liver tumors can be classified using SVM, and the accuracy is 83.33%. Noninvasive and micron-scale imaging can be achieved by X-ray ILPCI. We can observe hepatic tumors and small vessels from the phase-contrast images. This new imaging approach for hepatic cancer is effective and has potential use in the early detection and classification of hepatic tumors. © 2012 Tao et al.

Qian Z.Z.,Tianjin Medical University
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2011

To investigate the in vitro effect of bortezomib (BTZ) alone and in combination with pirarubicin (THP) on the growth inhibition of human cutaneous T-cell lymphoma cell line Hut-78. Hut-78 cells were cultured with different concentrations of BTZ or THP alone and the two drugs combination for 48 h. Cell proliferation, cell cycle and apoptosis were evaluated. The cell cycle inhibitor P21 was determined by Western blot. BTZ or THP alone significantly inhibited the growth of Hut-78 cells in a time- and dose-dependent manner. In the combination groups, the inhibitory effect of BTZ followed by THP was the highest (P < 0.01). When the inhibition rate was more than 50%, the combination index analysis showed significant synergistic if treated with BTZ followed by THP or the two at the same time, but antagonistic if treated with THP followed by BTZ. With the inhibition rate increasing, only the synergistic effect of BTZ followed by THP was further increased. The apoptosis rate of BTZ followed by THP was higher than that of single agent each (P < 0.01). BTZ alone significantly increased the proportion of cells in G(2)/M phase (P < 0.01) in a dose-dependent manner and up-regulated the expression level of P21. Sequential THP notably enhanced BTZ-induced cell cycle arrest and apoptosis. BTZ alone effectively induces growth inhibition and apoptosis of Hut-78 cells in vitro. BTZ followed by THP can synergistically enhance this cytotoxic effect. The mechanism may be that THP enhances BTZ-induced G(2)/M arrest and P21 up-regulation.

Li N.,University of Leicester | Li N.,Tianjin Medical University | Lu J.,University of Leicester | Willars G.B.,University of Leicester
PLoS ONE | Year: 2012

Glucagon-like peptide-1 (GLP-1) released from intestinal L cells in response to nutrients has many physiological effects but particularly enhances glucose-dependent insulin release through the GLP-1 receptor (GLP-1R). GLP-1 7-36 amide, the predominant circulating active form of GLP-1, is rapidly truncated by dipeptidyl peptidase-4 to GLP-1 9-36 amide, which is generally considered inactive. Given its physiological roles, the GLP-1R is targeted for treatment of type 2 diabetes. Recently 'compound 2' has been described as both an agonist and positive allosteric modulator of GLP-1 7-36 amide affinity, but not potency, at the GLP-1R. Importantly, we demonstrated previously that exendin 9-39, generally considered a GLP-1R antagonist, enhances compound 2 efficacy (or vice versa) at the GLP-1R. Given that GLP-1 9-36 amide is the major circulating form of GLP-1 post-prandially and is a low affinity weak partial agonist or antagonist at the GLP-1R, we investigated interaction between this metabolite and compound 2 in a cell line with recombinant expression of the human GLP-1R and the rat insulinoma cell line, INS-1E, with native expression of the GLP-1R. We show compound 2 markedly enhances efficacy and potency of GLP-1 9-36 amide for key cellular responses including AMP generation, Ca2+ signaling and extracellular signal-regulated kinase. Thus, metabolites of peptide hormones including GLP-1 that are often considered inactive may provide a means of manipulating key aspects of receptor function and a novel therapeutic strategy. © 2012 Li et al.

Tao Y.J.,Tianjin Medical University
Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology | Year: 2011

To investigate the effect of micro RNA-21 (miRNA-21) knocking on the Tb3.1 human tongue squamous cell carcinoma growth. Anti-sense miRNA-21 oligonucleotide was delivered with oligofectamine to suppress Tb 3.1 tongue cancer cell growth in vitro. Real-time polymerase chain reaction (PCR) was conducted to detect the miRNA-21 expression after transfection. Methyl thiazolyl tetrazolium (MTT) assay was used to determine Tb 3.1 cell survival rate. Apoptosis were examined by flow-cytometry. Matrigel matrix and transwell assay were used to determine Tb 3.1 cell colony formation and migration ability. Antigen KI-67 (Ki67), B cell lymphoma (Bcl-2), phosphatase and tensin homolog (PTEN), matrirx metalloproteinase 2 (MMP-2, MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) protein expression in Tb 3.1 cell were measured by Western blotting. miRNA-21 expression was decreased in miRNA-21 antisense oligonucleotide (ASODN) group. The survival rate of Tb 3.1 cells with AS-miRNA-21 transfection was significantly suppressed (F = 27.02, P = 0.00) and early phase apoptosis (F = 26.641, P = 0.001) induced in Tb 3.1 cell. Ki67, Bcl-2, MMP-2 and MMP-9 protein were down regulated while PTEN and TIMP-1 protein expression was increased. Blocking miRNA-21 expression in Tb3.1 cell could suppress cancer cell growth in vitro and miRNA-21 can serve as a novel target candidate for human tongue cancer gene therapy.

Doiron B.,University of Texas Health Science Center at San Antonio | Hu W.,University of Texas Health Science Center at San Antonio | Hu W.,Tianjin Medical University | Norton L.,University of Texas Health Science Center at San Antonio | Defronzo R.A.,University of Texas Health Science Center at San Antonio
Diabetologia | Year: 2012

Aims/hypothesis: The physiological significance of growth factor receptor-bound protein-10 (GRB10) in the pancreas is unclear. We hypothesised that GRB10 is involved in pancreatic apoptosis, as GRB10 binds with a family of cell-survival-related proteins implicated in apoptosis. Methods: Lentiviral vector small hairpin RNA (shRNA) targeting Grb10 was injected in vivo via an intraductal pancreatic route to target pancreatic tissues in adult mice, which were studied 2 weeks post-injection. Results: Using the TUNEL assay, we demonstrated for the first time that in vivo injection of lentivirus shRNA Grb10 directly into the adult mouse pancreas induced apoptosis in both exocrine and endocrine (alpha and beta) cells. This effect was more pronounced in alpha cells. Levels of the pro-apoptotic protein BCL2-interacting mediator of cell death (BIM) in islets was higher in lentivirus shRNA Grb10 than in lentivirus shRNA scramble mice. In the apoptotic pathway, BIM initiates apoptosis signalling, leading to activation of the caspase cascade. We propose that, when complexed with GRB10, BIM is inactive. On activation by stress signalling or, in the present study, following injection of lentivirus shRNA Grb10 into pancreas, BIM becomes unbound from GRB10 and activates the caspase cascade. Indeed, caspase-3 activity in islets was higher in the experimental than in the control group. Apoptosis induced by shRNA Grb10 resulted in a 34% decrease in fasting plasma glucagon. Mice injected with shRNA Grb10 had improved glucose tolerance despite reduced insulin secretion compared with shRNA scramble control mice. Conclusions/interpretation: GRB10 is critically involved in alpha cell survival and, as a result, plays an important role in regulating basal glucagon secretion and glucose tolerance in adult mice. © 2012 Springer-Verlag.

Wang G.,Tianjin Medical University
Zhonghua nan ke xue = National journal of andrology | Year: 2010

OBJECTIVE: The purpose of this study was to construct a pathway-based network using differentially expressed genes in prostate cancer (PCa) screened by cDNA microarray chips in domestic research to visualize the relations among the genes obtained from the microarray data, and identify the genes with significant influence on this network by statistical analysis. It also aimed to search for the genes that play key roles in the tumorigenesis of PCa, and probe into the molecular mechanism of PCa pathogenesis in Chinese men. METHODS: The relevant domestic literature of recent years were reviewed to sum up differentially expressed genes in PCa according to the screened microarray data. The OMIM database was used to analyze the relations among these genes and build a network of biological pathway. Furthermore, a statistical method, namely node contraction, was employed to compare the importance of the key genes. RESULTS: According to the gene expression profiling data, there were 113 differentially expressed genes, 51 up-regulated and 62 down-regulated. A pathway-based network including 68 inter-related genes was constructed using the OMIM database. The importance of every key node was calculated using the method of node contraction, and 12 key genes were identified, incuding c-MYC, VEGF, HSPCA, TGFbeta1, RANTES, EGR1, etc, which probably played important roles in the pathogenesis and progression of prostate cancer. CONCLUSION: We applied bioinformatics to the analysis of the gene expression profiling data in China, constructed a network of the differentially expressed genes using the OMIM database and method of node contraction, appraised the importance of the key genes, and established a method for the overall analysis of the gene chip data, which have paved a new ground for further researches on the pathogenesis of prostate cancer in Chinese men.

Xie F.,Tianjin Medical University
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2011

To investigate the in vitro effect of iron overload on the generation of reactive oxygen species (ROS) and of bone marrow (BM) cell function. BM mononuclear cells (BMMNCs) were cultured with ferric citrate (FAC) at different concentrations and for different time to create iron overload and confirmed by the detection of cellular labile iron pool (LIP). The changes of ROS, apoptosis, hematopoietic colony formation (CFU-E, BFU-E, CFU-GM and CFU-mix) and the percentage of the CD34 + cells percentage were analyzed. The differences of these index were tested after the iron overload treated with deferasirox (DFO) or antioxidants (N-acetyl-L-cysteine, NAC). 1) When BMMNCs were cultured with FAC, the LIP was found to increase in a time and concentration dependent manner. The intracellular LIP reached maximum at 400 micromol/L of FAC for 24 hours. 2) The ROS of total cells, leukocytes and erythrocytes increased to 1.77, 1.75 and 2.12 fold respectively compared with that of normal control when cells were cultured at 400 micromol/L of FAC for 24 hours . DFO and NAC could reduce the ROS efficiently (P<0.05). 3) The apoptotic rates of the FAC treated cells [(24.80 +/- 2.99)%] increased significantly compared with that of normal control [(8.90 +/- 0.96)%]. The capacity of hematopoietic colony formation in FAC treated cells decreased markedly compared with that of normal control (P<0.05). The percentage of CD34+ cells of FAC treated cells [(0.39 +/- 0.07)%] also decreased significantly compared with that of normal control [(0.91 +/- 0.12)%]. And these changes could be recovered by addition of NAC or DFO. Iron overload can affect the hematopoiesis by inducing the generation of ROS and this damage could be corrected by removing the excess iron and ROS of the BM cells. These findings might improve the treatment of dyshematopoiesis in patients with iron overload.

Yang P.,Tianjin Medical University
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2013

To explore the feasibility of volume perfusion CT imaging to dynamically monitor and evaluate the response of rabbit VX2 soft-tissue tumor to antiangiogenic treatment. To establish an experimental animal model of VX2 soft tissue tumor on 20 New Zealand white rabbits. Twenty rabbits were randomly divided into 2 groups. The therapy group was treated with recombinant human endostatin (3 mg·kg-1·d-1) for 7 days, and the control group received saline in the same dose only. Four times of CT volume perfusion scan were performed before treatment and on the second, forth, seventh days of treatment, respectively. The value of blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability (PMB) in the VX2 tumors were measured after scanning. The microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in the tumors were determined using immunohistochemical staining. The tumor volume of the therapy group was (1.36 ± 0.73) cm3 on the forth day of treatment and (1.69 ± 0.68) cm3 on the seventh day of the treatment. The tumor volume of the control group was (2.35 ± 0.62) cm3 on the fourth day of treatment and (3.87 ± 0.93) cm3 on the seventh day of the treatment (P < 0.05). On the seventh day of treatment, tumor necrosis ratio of the therapy group and the control group was (25.58 ± 5.51)% and (42.93 ± 4.34)%, respectively (P < 0.05). Comparing the perfusion parameters between the two groups on the same day, and the second, forth, seventh days of treatment, the value of PMB of the therapy group was (70.36 ± 23.46) ml·100 ml-1·min-1, (79.64 ± 13.68) ml·100 ml-1·min-1 and (84.76 ± 3.55) ml·100 ml-1·min-1, respectively, and that in the control group was (26.61 ± 6.47) ml·100 ml-1·min-1, (33.74 ± 16.47) ml·100 ml-1·min-1 and (30.47 ± 10.64) ml·100 ml-1·min-1, respectively (P < 0.05). The value of BF in the therapy group and control group was (71.19 ± 12.21) ml·100 ml-1·min-1 and (43.56 ± 12.21) ml·100 ml-1·min-1, respectively, on the seventh day of treatment (P < 0.05). The parameters on different days in the same group were compared. In the control group, the value of BF on the seventh day of treatment was significantly lower than that before and on the second and forth days of treatment (P < 0.05). However, in the therapy group, the value of PMB on the second, forth, and seventh days of treatment was significantly higher than that before treatment (P < 0.05). MVD of tumor in the control group was increased gradually, whereas increased on the first day and then decreased more in the therapy group. The VEGF expressions did not differ significantly between the experimental and control groups. Volume perfusion CT is helpful to quantify the tumor perfusion and evaluate the functional changes of tumor vasculature, and then evaluate the early therapeutic effect of antiangiogenic treatment.

Yu Z.,Tianjin Medical University
Chinese Journal of Clinical Oncology | Year: 2014

Surgery is one of the first choices in treating esophageal cancer. Anemia, impaired immunity, and infection caused by malnutrition play important roles in the subsequent occurrence of infection, trauma, and organ failure after surgery. Pre-operative nutritional risk assessment and reasonable choice of postoperative nutritional approach can significantly improve the nutritional status and reduce the possibility of the occurrence of infection, electrolyte imbalance, and organ failure. Enteral nutrition is recommended for those who can tolerate nutritional administration through this manner rather than parenteral nutrition because it is simple, economic, secure, and causes significantly few complications. Parenteral nutrition is adapted when enteral nutrition alone cannot meet the need for nutrient supply. In this article, the applications of postoperative nutritional support in esophageal cancer patients are summarized.

Xu Y.L.,Tianjin Medical University
Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology | Year: 2010

To observe the influence of H102 on the expression of amyloid protein and amyloid precursor protein in the hippocampus of APP695 transgenic mice. The 9-month-old APP695 transgenic mice were randomly divided into the model group and the H102 group; C57BL/6J mice were adopted as normal control group. The H102 group were injected with H102 in a dose of 3 microl/per mouse in lateral ventricle, once a day, for ten days; while the model group and the control group were injected with saline. The hippocampus and temporal cortex of the brain sections from transgenic mice and wild type female mice were subjected to immunohistochemistry and Congo red histological staining, and observed the difference of the protein expression under microscope. The expression of the APP protein was detected by Western blot. Abeta and APP immunohistochemistry showed density of positive cell in the CA1 region of hippocampus of control group were less than model group. H102 peptide reduced the area, and density of positive cells. Congo red staining showed there were lots of amyloid plagues in the brains of model mice but not in the brains of normal control. And the Western blot showed the content of the APP protein of the model group was much higher than the H102 group. H102 significantly decreased the amyloid plagues. The expression of APP, Abeta are increased in APP695 transgenic mice, and H102 can decrease the level of APP, Abeta in transgenic mice.

Men J.,Tianjin Medical University
Chinese Journal of Oncology | Year: 2015

Objective: To assess the value of thrombotic biomarkers in estimation of venous thromboembolism (VTE) risk in cancer patients. Methods: A total of 1473 cancer patients treated in the Tianjin Medical University General Hospital from 2009 to 201 were selected, including 845 males and 628 females in the age of 56± 17 years. The activities of von Willebrand factor antigen (vWF: Ag), factor VII (F VII:A), factor VIII (FVIII:A), antithrombin (AT:A), protein C (PC:A) and protein S (PS:A) were assayed using an ACL TOP 700 blood coagulation analyzer. The level of D-dimer (D-D) was assayed using the Biomerieux Mini Vidas Automated Immunoassay Analyzer. Receiver operating characteristic curve (ROC) was used to analyze the diagnostic performance of the parameters. Cox regression analysis model was applied to evaluate the effect on prognosis, and Kaplan-Meier curve was used to implement the survival analysis. Results: The levels of vWF:Ag, D-D, and FVIII:A were significantly higher in all the specified tumor groups (except the other tumor group) than that of the control groups (P < 0.05). F VIII: A was significantly higher than that in the control group in all tumor groups except the renal carcinoma, prostatic cancer, lymphoma groups and the other tumor group (P <0.05). The PC:A level was significantly lower in all tumor patients groups than in the control group, except glioma, breast cancer, gastric carcinoma, renal carcinoma and the other tumors groups (P<0.05). The PS: A level was significantly lower in all tumor groups than in the control group, except the glioma, breast cancer, prostatic cancer, lymphoma and the other tumors groups (P<0.05). The AT:A level was significantly lower in all tumor groups than in the control group (P<0.05). When the optimum cut-off point of vWF:Ag for VTE diagnosis was 192% in the cancer group, the area under ROC curve = 0.828 (95% CI; 0.716 to 0.939). When the optimum cut-off point of D-dimer for VTE diagnosis was 1484 ng/ml in the cancer group, the area under ROC curve = 0.915 (95% confidence interval: 0. 840 to 0.988). When the optimum cut-off point of PC: A for VTE diagnosis was 75.2% in the cancer group, the area under ROC curve = 0.764 (95% confidence interval: 0.630 to 0.898). The Cox analysis showed that age, surgery, chemotherapy and D-dimer were independent risk factors for VTE event within three months in cancer patients. The cumulative probability of VTE was increased significantly in the cancer patients if whose plasma D-dimer level was over the cut-off value. Conclusions: The plasma D-dimer level is obviously increased in cancer patients, and there is a relevance to thrombosis risk stratification and VTE cumulative probability. It is with good diagnostic performance, and may be used as an effective marker in estimation of VTE risk within 3 months in cancer patients.

Li Y.,Tianjin Medical University
Journal of Hard Tissue Biology | Year: 2013

Increasing evidence suggests an association between periodontal disease and low birthweight (LBW). We previously studied the effect of lipopolysaccharide (LPS) from periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) on human trophoblasts, and found that Aa-LPS induces apoptosis via the mitochondria-dependent pathway. This effect may contribute to the pathogenesis of periodontitis-associated LBW. In the present study, we observed the human placental trophoblast-like BeWo cells' response to Aa-LPS. Human placental trophoblast-like BeWo cells were cultured and treated with Aa-LPS. The time-dependant effects of Aa-LPS on cultured BeWo cells were studied using the Affymetrix GeneChipTM system (human; ca. 39500 genes). Reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time PCR analysis of gene expression were also carried out to confirm the DNA microarray results. In BeWo cells, Aa-LPS altered many gene expressions including the alpha subunit of the heterotrimeric G protein that stimulates adenylyl cyclase (GNAS) mRNA level. The reduction of GNAS gene expression by Aa-LPS was successfully confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time PCR. In conclusion, since GNAS was found to be particularly important to placental and fetal growth, the reduction of GNAS gene expression by Aa-LPS may be involved in growth retardation of the fetus, and may be the molecular basis of the mechanism of periodontitis-associated LBW. © 2013 The Hard Tissue Biology Network Association Printed in Japan, All rights reserved.

Dong W.,Tianjin Medical University
Sheng li xue bao : [Acta physiologica Sinica] | Year: 2011

The present study aims to investigate the effects of soluble endoglin (sEng) on invasive ability of cultured cytotrophoblasts of first trimester of pregnancy. Cytotrophoblasts of normal 6 to 8-week pregnancy were cultured by trypsin digestion method, and were incubated with cell culture medium without (control group) and with 10 μg/L sEng (sEng group), respectively for 24 h. The invasive ability was determined by transwell invasion assay, and expressions of MMP-2, MMP-9 mRNA and protein were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. The results showed that the invasive ability of cytotrophoblasts in sEng group was lower than that in control group (P < 0.05). Compared with control group, the expressions of MMP-2 and MMP-9 mRNA and protein of cytotrophoblasts were significantly lower (P < 0.05). In conclusion, sEng may participate in the genesis of preeclampsia by affecting the invasive ability of cytotrophoblasts through regulation of the expression of MMP-2 and MMP-9.

To study dynamic changes in gene expression and protein synthesis of runt-related transcription factor-2 (Runx2), Osterix and AJ18 in the femoral head of steroid-induced osteonecrosis in rats. Forty mature Wistar rats, 250-270 g (mean, 260 g) in weight, were randomly divided into model (30 rats) and control groups (10 rats). An early rat model of femoral head necrosis (FHN) was created by weekly injections of dexamethasone (20 mg/kg) into alternate sides of the gluteus maximus and twice-weekly training on a laboratory animal treadmill for 8 weeks. Hematoxylin and eosin (HE) staining was used to determine whether osteonecrosis had been successfully induced, and the model was then divided into equal 8, 10 and 12 week groups. At the end of the appropriate time period, total RNA and total protein were extracted from the femoral heads, and then real-time quantitative polymerase chain reaction and Western blot were performed to detect dynamic changes in the expression of Runx2, Osterix and AJ18 and protein synthesis in femoral heads with steroid-induced osteonecrosis in rats. At the post-modeling eighth, tenth and twelfth week, expression of Runx2 mRNA, Osterix mRNA and related protein synthesis were significantly down-regulated compared to that of the control group, which showed a downward trend with time; while expression of AJ18 mRNA and protein synthesis in the model group was much higher than in the control group, which showed an upward trend with time. Glucocorticoids may induce femoral head osteonecrosis by down-regulating Runx2/Osterix mRNA and up-regulating AJ18 mRNA. © 2010 Tianjin Hospital and Blackwell Publishing Asia Pty Ltd.

Hernandez S.L.,Harvard University | Gong J.H.,Harvard University | Chen L.,Harvard University | Chen L.,Tianjin Medical University | And 4 more authors.
Diabetes Care | Year: 2014

OBJECTIVE: We characterized and correlated endothelial progenitor cells (EPCs) and circulating progenitor cells (CPCs) with lack of vascular complications in the Joslin Medalist Study in patients with type 1 diabetes for 50 years or longer. RESEARCH DESIGN AND METHODS: EPC and CPC levels were ascertained by flow cytometry and compared among Medalists (n = 172) with or without diabetic retinopathy (DR; n = 84 of 162), neuropathy (n = 94 of 165), diabetic nephropathy (DN; n = 18 of 172), cardiovascular disease (CVD; n = 63 of 168), age-matched controls (n = 83), type 2 diabetic patients (n = 36), and younger type 1 diabetic patients (n = 31). Mitogens, inflammatory cytokines, and oxidative markers were measured in blood or urine. Migration of culture dperipheral blood mononuclear cells (PBMCs) from Medalists and age-matched controls were compared. RESULTS: Medalists' EPC and CPC levels equaled those of their nondiabetic age-matched controls, were 10% higher than those in younger type 1 diabetic patients, and were 20% higher than those in age-matched type 2 diabetic patients. CPC levels were 15% higher in Medalists without CVD and nephropathy than in those affected, whereas EPC levels were significantly higher in those without peripheral vascular disease (PVD) than those with PVD. Stromal-derived factor 1 (SDF-1) levels were higher in Medalists with CVD, DN, and DR than in those not affected and their controls. IGF-I levels were lower in Medalists and correlated inversely with CPC levels. Additionally, cultured PBMCs from Medalists migrated more than those from nondiabetic controls. CONCLUSIONS: Normal levels of EPC and CPC in the Medalists, unlike other groups with diabetes, especially those without CVD, support the idea that endogenous factors exist to neutralize the adverse effects of metabolic abnormalities of diabetes on vascular tissues. © 2014 by the American Diabetes Association.

Liu G.M.,Tianjin Medical University
International journal of surgical pathology | Year: 2012

Multilocular cystic renal cell carcinoma (MCRCC) is an uncommon low-grade renal cell carcinoma with unique morphologic features. The 2004 World Health Organization classification of kidney tumors categorized MCRCC as a separate entity. The authors report the case of a 48-year-old man whose MCRCC originated from the lower portion of the duplex kidney (DK). Because the oncological outcome of MCRCC is favorable, regardless of tumor size and stage, patients with MCRCC might benefit from nephron-sparing surgery. It is important to distinguish larger MCRCCs from other renal cell carcinomas, especially when comorbid with DK, because the characteristic anatomy of DK warrants the nephron-sparing surgery. To the authors' knowledge, MCRCC in DK has not been reported previously in the English literature.

Liu Y.,Tianjin Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2012

To investigate the relationship between the epithelial growth factor receptor (EGFR) mutation status and clinicopathological factors, and to analyze the mutation on the effect in non-small cell lung cancer (NSCLC) after surgery. The NSCLC patients who were resected and detected EGFR gene from March 2009 to March 2011 were retrospectively reviewed. The relationship between EGFR mutation status and clinicopathological factors, tumor markers, prognostic was analyzed. The mutation and the wild group had 169 and 214 patients respectively. EGFR mutation in female, non-smoking, adenocarcinoma and less than 60 years old accounted for 63.91%, 61.54%, 88.76% and 62.13% with statistical significance compared with male (χ(2) = 53.490, P = 0.000), smoking (χ(2) = 48.568, P = 0.000), non-adenocarcinoma (χ(2) = 105.560, P = 0.000) and more than 60 years old (χ(2) = 6.057, P = 0.017). Disease free survival (DFS) of the wild group was better than mutation group (χ(2) = 11.329, P = 0.001). In addition, there were some relations between mutation status and excision repair cross complementing (ERCC1) protein, carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) and Cyfra21-1. ERCC1(+) (χ(2) = 6.739, P = 0.012), SCC(χ(2) = 16.839, P = 0.000) and Cyfra21-1(χ(2) = 6.638, P = 0.013) more than normal value was common in wild group. Increased CEA was common in mutation group (χ(2) = 5.436, P = 0.023). EGFR mutation is commonly found in female, non-smoking, adenocarcinoma and less than 60 years old NSCLC patients. The wild group obtains better DFS than mutation group. Tumor markers may predict the mutation status, which need further research.

Liao Z.,Tianjin University | Liao Z.,China Institute of Technology | Wang H.,Tianjin University | Wang X.,China Institute of Technology | And 4 more authors.
Advanced Functional Materials | Year: 2011

A multifunctional nanoscale platform that is self-assembled from a hydrophobic poly(dl-lactide-coglycolide)(PLGA) core and a hydrophilic paramagnetic-folate-coated PEGylated lipid shell (PFPL; PEG=polyethylene glycol) is designed for simultaneous magnetic resonance imaging (MRI) and targeted therapeutics. The nanocomplex has a well-defined core-shell structure which is studied using confocal laser scanning microscopy (CLSM). The paramagnetic diethylenetriaminepentaacetic acid-gadolinium (DTPA-Gd) chelated to the shell layer exhibits significantly higher spin-lattice relaxivity (r1) than the clinically used small-molecular-weight MRI contrast agent Magnevist®. The PLGA core serves as a nanocontainer to load and release the hydrophobic drugs. From a drug-release study, it is found that the modification of the PLGA core with a polymeric liposome shell can be a useful tool for reducing the drug-release rate. Cellular uptake of folate nanocomplex is found to be higher than that of non-folate-nanocomplex due to the folate-binding effect on the cell membrane. This work indicates that the multifunctional platform with combined characteristics applicable to MRI and drug delivery may have great potential in cancer chemotherapy and diagnosis. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Liu J.,Tianjin Union Medicine Center | Wang F.,Tianjin Medical University | Shi S.,Tianjin Union Medicine Center
Helicobacter | Year: 2015

Background: Myocardial infarction is a fatal cardiovascular disease and one of the most common death causes all around the world. The aim of the meta-analysis was to quantify the risk of myocardial infarction associated with Helicobacter pylori infection. Methods: A literature search was performed to identify studies published before 14 July, 2014, for relevant risk estimates. Fixed and random effect meta-analytical techniques were conducted for myocardial infarction. Results: Twenty-six case-control studies involving 5829 myocardial infarction patients and more than 16,000 controls were included. Helicobacter pylori infection was associated with an increased risk of myocardial infarction (OR: 2.10, 95%CI: 1.75-2.53, p = .06). We also discovered a significant association between the bacteria and risk of myocardial infarction in young people (OR: 1.93, 95% CI: 1.41-2.66, p = .07), in elder people (OR: 2.02, 95% CI: 1.60-2.54, p = .29), in Caucasians (OR: 2.29, 95% CI: 1.99-2.63, p = .12), and in Asians (OR: 1.75, 95% CI: 1.12-2.73, p = .08). Conclusion: Our meta-analyses suggested a possible indication of relationship between Helicobacter pylori infection and the risk of myocardial infarction. The pathogenicity might not be affected by age and race. More researches should be conducted to explore the mechanisms involved. © 2014 John Wiley & Sons Ltd.

Wang F.,Tianjin Union Medicine Center | Liu J.,Tianjin Union Medicine Center | Lv Z.,Tianjin Medical University
Scandinavian Journal of Infectious Diseases | Year: 2013

Background: Helicobacter pylori infects more than half of the world's population. The aim of this study was to quantify the association between H. pylori infection and the risk of diabetes mellitus and diabetic nephropathy, and to detect at which stage the infection might have higher pathogenicity in the disease-free status-diabetes mellitus-diabetic nephropathy process. Methods: A literature search was performed to identify studies published between 1997 and 2012 for relative risk estimates. Fixed and random effects meta-analytical techniques were conducted for diabetes mellitus and diabetic nephropathy. Results: Thirty-seven case-control studies and 2 cohort studies were included. H. pylori was associated with an increased risk of each type of diabetes mellitus (odds ratio (OR) 2.00, 95% confidence interval (CI) 1.82-2.20, p for heterogeneity = 0.07). The infection was also associated with increased risks of type 1 and type 2 diabetes mellitus, separately (OR 1.99, 95% CI 1.52-2.60, p for heterogeneity = 0.15, and OR 2.15, 95% CI 1.81-2.55, p for heterogeneity = 0.24, respectively). In addition, we found a significant association between H. pylori infection and diabetic nephropathy risk (OR 1.60, 95% CI 1.10-2.33, p for heterogeneity = 0.44). Conclusions: Our meta-analyses suggest a relationship between H. pylori infection and the risk of diabetes mellitus and diabetic nephropathy. The bacterium may be able to play its pathogenic role in the whole disease process, and this action may be stronger in type 2 diabetic patients than in type 1 diabetic patients. © 2013 Informa Healthcare.

Zang M.F.,Tianjin Medical University
Zhonghua yi xue za zhi | Year: 2011

To compare the chemosensitivity of pirarubicin (THP) and epirubicin (EPI) in primary breast cancer (PBC) cells so as to examine their differential chemosensitivity to THP and EPI by CD-DST (collagen gel droplet embedded culture-drug sensitivity test) system; To detect the differences in the short-term clinical efficacy and side effects between TAC (docetaxel + pirarubicin + cyclophosphamide) and TEC (docetaxel + epirubicin + cyclophosphamide) as the neoadjuvant chemotherapy regimens and the long-term clinical efficacy of CAF (cyclophosphamide + pirarubicin + fluorouracil) and CEF (cyclophosphamide + epirubicin + fluorouracil) as the chemotherapy regimens in breast cancer; To evaluate the feasibility of THP as an adjuvant chemotherapeutic regimen in the treatment of breast cancer. From January 2008 to January 2009, a total of 129 fresh breast cancer samples were collected. The differential chemosensitivity of cultured PBC cells to THP and EPI was measured by CD-DST test. And 139 cases of PBC patients inIIb-IIIc phase were randomly divided into two groups: TAC and TEC groups. After 4-6 cycles of neoadjuvant chemotherapy, the primary lesion, axillary lymph nodes and side effects were assessed; The clinical data and survival status of 1241 cases of PBC patients treated at our hospital from 2003 to 2006 were collected and divided into CAF and CEF groups according to their chemotherapeutic regimens. Long-term prognosis was compared between two groups. There was no significant difference of chemosensitivity between THP and EPI in PBC cells (P = 0.743); The overall response rate (RR) of neoadjuvant chemotherapy was 87.8%; the clinical objective responses, pathologic complete remission (pCR), clinical complete remission (cCR), clinical partial remission (cPR) and stable disease (SD) of groups TAC and TEC were 88.7%, 11.3%, 28.2%, 60.6%, 11.3% vs 86.8%, 10.3%, 26.5%, 60.3%, 13.2% respectively. There was no significant difference between two groups (P > 0.05). No significant differences existed between two groups in such side effects as leukopenia, thrombocytopenia, constipation, cardiotoxity and hepatorenal dysfunction (P > 0.05). The gastrointestinal reactions of nausea and vomiting was less frequent in the TAC group than that in the TEC group (46.5% vs 66.2%, P = 0.019); There was no significant difference in 5-year disease-free survival rate (79% vs 78%) and overall survival rate between two groups (85% vs 82%, P > 0.05). There were no significant differences in chemosensitivity, clinical efficacy of neoadjuvant chemotherapy, side effects or long-term efficacy between THP and EPI. Both pirarubicin and epirubicin may be used as conventional chemotherapy in breast cancer.

Wang D.,Tianjin Medical University
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2011

To study the expressions of erythropoietin receptor (EPOR) and thrombopoietin receptor (TPOR) on CD34+ CD59- and CD34+ CD59+ bone marrow (BM) cells from patients with paroxysmal nocturnal hemoglobinuria (PNH). (1) The expressions of EPOR and TPOR on CD34+ CD59- and CD34+ CD59- BM cells from 26 PNH patients and 16 normal controls were examined by flow cytometry (FCM). (2) The mRNA expression of the EPOR and the TPOR in BM mononuclear cells (BMMNC) from 25 PNH patients and 13 normal controls were examined by RT-PCR. (1) The percentage of EPOR positive cells in PNH CD34+ CD59+ BMMNC [(30.67 +/- 18.30)%] was significantly higher than that in PNH CD34+ CD59- BMMNC [(8.05 +/- 3.51)%] (P < 0.01) and than that in control CD34+ CD59+ BMMNC [(8.24 +/- 6.51)%] (P < 0.01), but there was no obvious difference between the CD34+ CD59-BMMNC in PNH and CD34+ CD59+ BMMNC in control. (2) The percentage of TPOR positive cells in PNH CD34+ CD59+ BMMNC [(28.15 +/- 17.75)%] was significantly higher than that in PNH CD34+ CD59-BMMNC [(15.65 +/- 14.45)%] (P < 0.05) and than that in control CD34+ CD59+ BMMNC [(10.77 +/- .39)%] (P < 0.01), but there was no obvious difference between the CD34+ CD59- BMMNC in PNH and CD34+ CD59+ BMMNC in control. (3) There was no statistic difference in EPOR mRNA and TPOR mRNA expressions in BMMNCs between PNH patients group [(0.41 +/- 0.37) and (0.32 +/- 0.19), respectively] and control group [(0.47 +/- 0.33) and (0.40 +/- 0.29), respectively]. The expression of EPOR and TPOR of PNH patients on BM CD34+ CD59+ cells are significantly higher than those on BM CD34+ CD59- cells. The difference may be due to abnormal transcription of both receptor coding genes.

Liu Q.,Tianjin Medical University
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2011

To explore the occupational stress factors associated with the prevalence of metabolic syndrome (MS) among male policemen. Using cluster sampling method, we selected four Public Security Bureau within the jurisdiction of the station now in some city. All the male police were included as research objects, and finally 1490 persons were selected, health and occupational stress inventory-revised (OSI-R) questionnaire were used for epidemiological surveys, and anthropometric examination and chemical indicators were also measured at the same time. The analysis methods were chi-square test and unconditional logistical regression. Among the 1490 of research objects, 1483 completed the questionnaire, and 1480 of the eligible questionnaires were available.237 cases were MS, and the prevalence rate was 16.0%(237/1480). The number of cases who were high, moderate and lack of occupational stress in MS group were 8, 39 and 23, that in non-MS were 14, 114 and 131, respectively. The odds of occupational stress with the highest and medium among policemen than who were lack were 4.82 (95%CI: 1.50 - 15.41) and 3.33 (95%CI: 1.62 - 6.79); the average score of role ambiguity, role insufficiency and responsibility in the group of MS were (38.76 ± 6.83), (25.74 ± 7.22), (25.76 ± 6.27); and that in non-MS were (37.55 ± 6.85), (24.50 ± 6.58), (25.05 ± 5.95). The logistical regression analysis showed that: the likely three occupational risk stress factors which influencing the prevalence of MS were role ambiguity, role insufficiency and responsibility, and the OR (95%CI) were 1.06 (1.02 - 1.10), 1.04 (1.02 - 1.07) and 1.03 (1.01 - 1.06), respectively. Role ambiguity, role insufficiency and responsibility were the occupational risk stress factors associated with the prevalence of MS among male policemen.

The protein kinase C (PKC) family has been functionally linked to cancer. It has been suggested that atypical PKCs contribute to cell proliferation and cancer progression. With respect to breast cancer, PKCζ has been found to play a key role in intracellular transduction of mitogenic and apoptotic signals using mammary cell lines. However, little is known about its function in vivo. Here we examined the correlation between PKCζ protein levels and important clinicopathologic factors in breast cancer using patient samples. To conduct the study, 30 invasive ductal carcinoma cases and their paired normal tissues were used for tissue microarray analysis (TMA) and 16 were used for western blot analysis. In addition, the correlation between PKCζ expression levels and clinicopathologic characteristics was determined in 176 cases with relevant clinical data. Finally, the correlation between PKCζ and epithelial growth factor receptor 2 (HER2) expressions was determined using three breast cancer cell lines by western blot analysis. Both TMA and western blot results showed that PKCζ protein was highly expressed in primary tumors but not in paired normal tissue. The correlation study indicated that high PKCζ levels were associated with premenopausal patients (p = 0.019) and worse prognostic factors, such as advanced clinical stage, more lymph node involvement and larger tumor size. Both disease-free survival and overall survival rates were lower in the high PKCζ group than those in the low PKCζ group. No correlation was observed between PKCζ levels and age, histological grade, or estrogen or progesterone receptor expression status. A positive correlation between PKCζ and HER2 levels was observed in both tumor samples and cell lines. Our observations link PKCζ expression with factors pointing to worse prognosis, higher HER2 levels and a lower survival rate. This suggests that PKCζ protein levels may serve as a prognostic marker of breast cancer.

Xie K.L.,Tianjin Medical University
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences | Year: 2010

To investigate the effect of hydrogen gas inhalation on survival rate and serum high mobility group box 1 (HMGB1) levels in severe septic mice. Severe sepsis was induced by cecal ligation and puncture (CLP) operation in mice.A total of 248 mice were randomly divided into four groups: sham operation group (sham), sham operation with hydrogen gas inhalation group (sham+H2), severe CLP group (severe CLP) and severe CLP with hydrogen gas inhalation group (severe CLP+H2). Hydrogen gas inhalation was given for 1 h at 1st and 6th h after CLP or sham operation, respectively. The survival rates and serum HMGB1 levels of all groups at different time points were measured. The 7-d survival rates of severe CLP mice was 0 % (Compared with Sham group, P <0.05), and the serum HMBG1 levels from h2 to h32 after CLP operation were significantly increased in severe CLP mice (Compared with Sham group, P <0.05). Hydrogen gas treatment increased the 7-d survival rate of severe CLP mice to 60 % (Compared with severe sepsis group, P <0.05) and significantly reduced the serum HMGB1 levels at different time points (Compared with severe sepsis group, P <0.05). Hydrogen gas inhalation can decrease the serum HMGB1 levels and increase the survival rate of rats with severe sepsis.

Zhang H.T.,Tianjin Medical University
Zhonghua nan ke xue = National journal of andrology | Year: 2012

To explore the correlation of histologically proven prostatitis with the level of prostate specific antigen (PSA), prostate volume, PSA density (PSAD), international prostate symptom score (IPSS), maximum flow rate (Qmax) and post-void residual volume (PVR) in men with symptoms of benign prostate hyperplasia (BPH). Totally 673 patients surgically treated for BPH were divided into Groups A and B in accordance with histological findings, the former including those with histological prostatitis, and the latter without it. Comparisons were made between the two groups in the PSA level, prostate volume, PSAD, IPSS, Qmax and PVR. The PSA level, prostate volume, IPSS and PVR were significantly higher in Group A ([5.64 +/- 2.48] microg/L, [43.66 +/- 13.11] ml, 24.72 +/- 5.39 and [124.90 +/- 49.80] ml) than in B ([4.97 +/- 1.99] microg/L, [40.41 +/- 11.44] ml, 23.40 +/- 6.21 and [112.73 +/- 50.03] ml) (P<0.05), while Qmax markedly lower in the former ([6.94 +/- 3.23] ml/s) than in the latter ([7.75 +/- 3.52] ml/s) (P<0.05), but PSAD showed no statistically significant difference between the two groups (0.129 +/- 0.048 vs 0.123 +/- 0.034, P>0.05). Histological prostatitis can significantly increase the PSA level, prostate volume, IPSS and PVR, and reduce the Qmax of the patient, but is not correlated with PSAD. It is an important factor influencing the clinical progression of BPH.

Yang X.L.,Chinese University of Hong Kong | Yang X.L.,Tianjin Medical University | Ma R.C.W.,Chinese University of Hong Kong | So W.-Y.,Chinese University of Hong Kong | And 3 more authors.
Diabetes, Obesity and Metabolism | Year: 2012

Motivated by recent reports on associations between diabetes and cancer, many researchers have used administrative databases to examine risk association of cancer with drug use in patients with diabetes. Many of these studies suffered from major biases in study design and data analysis, which can lead to erroneous conclusions if these biases are not adjusted. This article discusses the sources and impacts of these biases and methods for correction of these biases. To avoid erroneous results, this article suggests performing sensitivity and specificity analysis as well as using a drug with a known effect on an outcome to ascertain the validity of the proposed methods. Using the Hong Kong Diabetes Registry, we illustrated the impacts of biases of drug use indication and prevalent user by examining the effects of statins on cardiovascular disease. We further showed that 'immortal time bias' may have a neutral impact on the estimated drug effect if the hazard is assumed to be constant over time. On the contrary, adjustment for 'immortal time bias' using time-dependent models may lead to misleading results biased towards against the treatment. However, artificial inclusion of immortal time in non-drug users to correct for immortal time bias may bias the result in favour of the therapy. In conclusion, drug use indication bias and prevalent user bias but not immortal time bias are major biases in the design and analysis of drug use effects among patients with diabetes in non-clinical trial settings. © 2011 Blackwell Publishing Ltd.

Shi L.,U.S. National Institutes of Health | Shi L.,Tianjin Medical University | Oberdoerffer P.,U.S. National Institutes of Health
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2012

DNA double-strand breaks (DSBs) occur in the context of a highly organized chromatin environment and are, thus, a significant threat to the epigenomic integrity of eukaryotic cells. Changes in break-proximal chromatin structure are thought to be a prerequisite for efficient DNA repair and may help protect the structural integrity of the nucleus. Unlike most bona fide DNA repair factors, chromatin influences the repair process at several levels: the existing chromatin context at the site of damage directly affects the access and kinetics of the repair machinery; DSB induced chromatin modifications influence the choice of repair factors, thereby modulating repair outcome; lastly, DNA damage can have a significant impact on chromatin beyond the site of damage. We will discuss recent findings that highlight both the complexity and importance of dynamic and tightly orchestrated chromatin reorganization to ensure efficient DSB repair and nuclear integrity. This article is part of a Special Issue entitled: Chromatin in time and space. © 2012.

Kong D.-X.,Cancer Chemotherapy Center | Kong D.-X.,Tianjin Medical University | Yamori T.,Cancer Chemotherapy Center
Acta Pharmacologica Sinica | Year: 2010

JFCR39 is an informatic anticancer drug discovery system that utilizes a panel of 39 human cancer cells coupled with a drug-activity database. This system not only provides disease-oriented information but can also predict the mechanism of action of a given antitumor agent. Development of a phosphatidylinositol 3-kinase (PI3K) inhibitor as an anticancer drug candidate has attracted a great deal of attention from both academia and industry because PI3K is known to be closely involved in carcinogenesis. ZSTK474 was identified as a PI3K inhibitor using JFCR39 system in combination with COMPARE analysis program. These findings were based on the similar fingerprint (growth inhibition profiles for JFCR39 human cancer cell line panel) with that of a classical PI3K inhibitor LY294002. Biochemical experiments confirmed ZSTK474 to be a potent pan-class I PI3K inhibitor, with high selectivity over other classes of PI3K and protein kinases. We previously reported the in vitro and in vivo antitumor efficacy of ZSTK474, together with the G 0 /G 1 arrest and antiangiogenic activity. Here, we review the JFCR39 system and summarize recent studies on PI3K biology and the development of PI3K inhibitors before discussing ZSTK474 in some detail. © 2010 CPS and SIMM All rights reserved.

Fu W.,University of Pennsylvania | Fu W.,Tianjin Medical University | Madan E.,University of Pennsylvania | Yee M.,University of Pennsylvania | Zhang H.,University of Pennsylvania
Biochimica et Biophysica Acta - Reviews on Cancer | Year: 2012

Prostate cancer remains the most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in men in the United States. The current standard of care consists of prostatectomy and radiation therapy, which may often be supplemented with hormonal therapies. Recurrence is common, and many develop metastatic prostate cancer for which chemotherapy is only moderately effective. It is clear that novel therapies are needed for the treatment of the malignant forms of prostate cancer that recur after initial therapies, such as hormone refractory (HRPC) or castration resistant prostate cancer (CRPC). With advances in understanding of the molecular mechanisms of cancer, we have witnessed unprecedented progress in developing new forms of targeted therapy. Several targeted therapeutic agents have been developed and clinically used for the treatment of solid tumors such as breast cancer, non-small cell lung cancer, and renal cancer. Some of these reagents modulate growth factors and/or their receptors, which are abundant in cancer cells. Other reagents target the downstream signal transduction, survival pathways, and angiogenesis pathways that are abnormally activated in transformed cells or metastatic tumors. We will review current developments in this field, focusing specifically on treatments that can be applied to prostate cancers. Finally we will describe aspects of the future direction of the field with respect to discovering biomarkers to aid in identifying responsive prostate cancer patients. © 2011 Elsevier B.V.

Cole A.J.,University of Michigan | Yang V.C.,University of Michigan | Yang V.C.,Tianjin Medical University | David A.E.,University of Michigan | David A.E.,Industrial Science and Technology Network Inc.
Trends in Biotechnology | Year: 2011

Interest in utilizing magnetic nanoparticles (MNP) for biomedical applications has increased considerably over the past two decades. This excitement has been driven in large part by the success of MNPs as contrast agents in magnetic resonance imaging. The recent investigative trend with respect to cancer has continued down a diagnostic path, but has also turned toward concurrent therapy, giving rise to the distinction of MNPs as potential " theranostics" Here we review both the key technical principles of MNPs and ongoing advancement toward a cancer theranostic MNP. Recent progress in diagnostics, hyperthermia treatments, and drug delivery are all considered. We conclude by identifying current barriers to clinical translation of MNPs and offer considerations for their future development. © 2011 Elsevier Ltd.

Schernhammer E.S.,Harvard University | Schernhammer E.S.,Ludwig Boltzmann Research Institute | Feskanich D.,Harvard University | Liang G.,Harvard University | And 3 more authors.
American Journal of Epidemiology | Year: 2013

The risk of lung cancer among night-shift workers is unknown. Over 20 years of follow-up (1988-2008), we documented 1,455 incident lung cancers among 78,612 women in the Nurses' Health Study. To examine the relationship between rotating night-shift work and lung cancer risk, we used multivariate Cox proportional hazard models adjusted for detailed smoking characteristics and other risk factors. We observed a 28% increased risk of lung cancer among women with 15 or more years spent working rotating night shifts (multivariate relative risk (RR) = 1.28, 95% confidence interval (CI): 1.07, 1.53; Ptrend = 0.03) compared with women who did not work any night shifts. This association was strongest for small-cell lung carcinomas (multivariate RR = 1.56, 95% CI: 0.99, 2.47; Ptrend = 0.03) and was not observed for adenocarcinomas of the lung (multivariate RR = 0.91, 95% CI: 0.67, 1.24; Ptrend = 0.40). Further, the increased risk associated with 15 or more years of rotating night-shift work was limited to current smokers (RR = 1.61, 95% CI: 1.21, 2.13; Ptrend < 0.001), with no association seen in nonsmokers (P interaction = 0.03). These results suggest that there are modestly increased risks of lung cancer associated with extended periods of night-shift work among smokers but not among nonsmokers. Though it is possible that this observation was residually confounded by smoking, our findings could also provide evidence of circadian disruption as a "second hit" in the etiology of smoking-related lung tumors. © The Author 2013.

Guo X.Y.,Tianjin Medical University
Zhonghua yi xue za zhi | Year: 2010

OBJECTIVE: To assess the anti-tumor immune response of cryoablation for prostate cancer. METHODS: Mouse model of prostate cancer was established. And the tumor-bearing mice were divided into three groups: control group (Group A), surgery group (Group B) and cryoablation group (Group C). Blood samples were withdrawn before and at Days 7, 14, 21 post-treatment. IFN-gamma and IL-4 were analyzed by enzyme-linked immunosorbent assay (ELISA). Th1/Th2 ratio was estimated from the IFN-gamma/IL-4 ratio. Lymphocytes of draining lymph node (DLN) and spleen were isolated. And the post-therapeutical number of tumor-specific IFN-gamma+CD4+ Th cells was measured by the method of enzyme link immunological spot (ELISPOT). And tumor-specific cytolytic activity of CD8+ cytotoxic T lymphocyte (CTL) was measured by LDH assay. The rate of metastasis was assessed. RESULTS: At Day 7 post-treatment in Groups A, B and C, Th1/Th2 ratio was 4.97+/-0.31, 10.07+/-0.62 and 13.71+/-0.57 respectively (P<0.05); the number of IFN-gamma+ cells every 10(6) CD4+ Th cells in DLN 22.3+/-1.0, 24.0+/-1.2 and 243.4+/-46.2 respectively; cytolytic activity of cytotoxic T lymphocyte against prostate cancer cells (14.6+/-1.1)%, (15.2+/-0.8)% and (62.6+/-2.3)% respectively (P<0.05). But for T cells derived from spleen, there were no difference in IFN-gamma+CD4+ Th cells or cytolytic activity of CTL among the groups. At Day 28 post-treatment, the rate of DLN metastasis was 100%, 80% and 40% respectively. And the rates of lung metastasis were all 100%. CONCLUSION: Cryoablation for prostate cancer can induce the Th1 advantage of anti-tumor immunity and generate the tumor-specific immune response in DLN. But the response remains limited. Further studies are warranted.

Wang H.,Tianjin University | Liu Z.,Tianjin University | Wang S.,Tianjin University | Dong C.,Tianjin University | And 3 more authors.
ACS Applied Materials and Interfaces | Year: 2014

In clinic, the application of photodynamic therapy (PDT) in deep tissue is severely constrained by the limited penetration depth of visible light needed for activating the photosensitizer (PS). In this Article, a merocyanine 540 (MC540) and upconverting nanoparticle (UCN) coloaded functional polymeric liposome nanocarrier, (MC540 + UCN)/FPL, was designed and constructed successfully for solving this problem in PDT. Compared with the conventional approaches using UCNs absorbing PSs directly, the combination of UCN and polymeric liposome has unique advantages. The UCN core as a transducer can convert deep-penetrating near-infrared light to visible light for activating MC540. The functional polymeric liposome shell decorated with folate as a nanoshield can keep the UCN and MC540 stable, protect them from being attacked, and help them get into cells. The results show that (MC540 + UCN)/FPL is an individual nanosphere with an average size of 26 nm. MC540 can be activated to produce singlet oxygen successfully by upconverting fluorescence emitted from UCNs. After (MC540 + UCN)/FPL was modified with folate, the cell uptake efficiency increased obviously. More interestingly, in the PDT effect test, the (MC540 + UCN)/FPL nanocarrier further improved the inhibition effect on tumor cells by anchoring targeting folate and transactivating transduction peptide. Our data suggest that the (MC540 + UCN)/FPL nanocarrier may be a useful nanoplatform for future PDT treatment in deep-cancer therapy based on upconversion mechanism. © 2014 American Chemical Society.

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

To investigate the impact of the Artemisia annua plant-derived drug, artesunate, on proliferation of primary rat hepatic stellate cells (HSCs), and to analyze the underlying molecular mechanisms of its anti-fibrogenic effects involving the inhibition of transforming growth factor-beta 1 (TGF-b1) expression and secretion in liver. Isolated, cultured, and activated primary rat HSCs were divided into sixteen groups, including one untreated control group and fifteen artesunate-treated experimental groups with 125, 150, 175, 200 or 225 mumol/L for 24, 48 or 72 hours. The rate of cellular proliferation was measured using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. TGF-b1 mRNA expression was evaluated by reverse transcription-polymerase chain reaction and protein expression was evaluated by Western blotting. Enzyme-linked immunosorbent assay was used to evaluate secreted levels of TGF-b1 protein. Artesunate significantly inhibited proliferation of cultured HSCs in a dose- and time-dependent manner (all, P less than 0.01). After 24 hours of exposure, the inhibition ratios of the various artesunate concentrations were: 6.06%+/-1.44% (125 mumol/L), 21.47%+/-5.57% (150 mumol/L), 42.00%+/-7.36% (175 mumol/L), 67.12%+/-4.55% (200 mumol/L), and 79.83%+/-3.67% (225 mumol/L). Artesunate significantly inhibited the TGF-b1 mRNA expression in HSCs, and the higher the drug concentration, the higher the degree of inhibition (all, P less than 0.01). In addition, artesunate significantly inhibited the expression of intracellular and secreted TGF-b1 protein (all, P less than 0.01). In response to artesunate (mumol/L concentrations), the TGF-b1 levels were (164.24+/-6.88) pg/ml (0μmol/L), (102.68+/-4.45) pg/ml (150μmol/L), (86.54+/-5.56) pg/ml (175μmol/L), and (56.55+/-5.66) pg/ml (200μmol/L). Artesunate exerts anti-fibrogenic effects on HSCs in vitro, possibly by reducing the expression, translation and secretion of TGF-b1.

Zhang J.,Tianjin Medical University
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2012

This study was purposed to establish and identify the model of extramedullary infiltration of CML-NOD/SCID mice. 24 mice were irradiated with 270 cGy of (137)Cs and absorbed dose rate 80 cGy/min, and were randomly divided into test group I, test group II and control group. The mice in test group I and test group II were injected with 5×10(6) and 1×10(7) K562 cells per mouse respectively, the mice in control group were injected with 0.2 ml of normal saline. The general situation and survival time of these mice were monitored, the extramedullary infiltration of leukemia cells was detected by histopathology examination and RT-PCR. The results indicated that at 4 - 8 weeks after injection, all the mice of group I and group II displayed extramedullary infiltration, suggesting that CML/NOD-SCID model was successfully established. It is concluded that the model of extramedullary infiltration of CML/NOD-SCID mice can be established by injection K562 cells into caudal vein, and can be confirmed by histopathologic examination and detection of BCR-ABL fusion gene using RT-PCR.

Ge P.,Tianjin Medical University | Xiao G.,Ningbo University
OncoTargets and Therapy | Year: 2016

Non-small-cell lung cancer (NSCLC) has a multifactorial pathogenesis, and the genetic background may be one of the critical etiologic factors. Interleukin (IL)-27, a novel member of the IL-12 family, plays a vital role in antitumor immunity. The aim of the current study was to determine the association of a single nucleotide polymorphism of the IL-27 gene with the risk of NSCLC. The genotype of the IL-27 rs153109 polymorphism was analyzed in 388 patients with NSCLC and 390 healthy controls by using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. In the patients with NSCLC, the frequencies of the GG, GA, and AA genotypes and the G and A alleles were 14.0%, 56.4%, 29.6%, 42.1%, and 57.9%, respectively. There were no significant differences in the genotype and allele distributions of the IL-27 rs153109 polymorphism between the patients with NSCLC and healthy controls (P.0.05). Furthermore, no association was determined between this polymorphism and different clinical characteristics in patients with NSCLC. Taken together, these findings suggest that the IL-27 gene may not be involved in the development of NSCLC in the Chinese population. © 2016 Ge and Xiao.

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

To construct a retroviral vector containing rat δNδC/VEGFand verify its expression in RAW 264.7 cells. The ddVEGF-C gene was amplified by polymerase chain reaction (PCR) from pSecTag-ddVEGF-C and cloned into pLPCX vector. After the procedure of PCR, double enzyme digestion analysis and DNA sequencing, the recombinant plasmid was transfected into packaging cells PT67 using Lipofectamine(TM); 2000, and the positive clones were collected by means of puromycin selection and detected for the viral titer. The expression of ddVEGF-C mRNA and protein in the RAW264.7 cells was determined by RT-PCR and Western blotting, respectively. PCR and double enzyme digestion analysis demonstrated that the recombinant pLPCX-ddVEGF-C was successfully constructed by displaying two positive bands of 382 bp and 6 191 bp as expected. Viral titer was 2×10(7); CFU/mL. RT-PCR and Western blotting showed the expression of ddVEGF-C at the mRNA and protein levels in RAW 264.7 cells. The recombinant vector pLPCX-ddVEGF-C has been successfully constructed as well as PT67 packaging cells expressing stably ddVEGF-C, which provides a potential tool for further VEGF-C related study.

Pan J.G.,Dong - A University | Zhou X.,Dong - A University | Luo R.,Dong - A University | Han R.F.,Tianjin Medical University
Medical Oncology | Year: 2012

Novel treatment strategies such as gene therapy are warranted in view of the failure of current treatment approaches to cure a high percentage of patients with advanced bladder cancers. The emergence of cancer gene therapy potentially offers a number of exciting treatments. The majority of approaches involve strategies to suppress the function of activated oncogenes to restore the expression of functional tumour suppressor genes or to initiate tumour self-destruction. One gene therapy approach against tumours that holds great promise is suicide gene therapy. Herpes simplex virus thymidine kinase (HSV-TK) phosphorylates ganciclovir (GCV), which in turn interacts with cellular DNA polymerase and interferes with DNA synthesis to cause death of rapidly dividing cells. The development of an effective delivery system is absolutely critical to the usefulness and safety of gene therapy. At present, the adeno-associated virus (AAV) vector has the most promising potential in view of its non-pathogenicity, wide tropisms and long-term transgene expression in vivo. Gene therapy studies using different serotypes of recombinant AAV (rAAV) as delivery vehicles have proved rAAVs to be an effective modality of cancer gene therapy. In the present study, we investigated the suppression effect of AAV-mediated HSV-TK/GCV system on the bladder cancer cells and in mice xenograft models of bladder cancer. Our data demonstrate that rAAV-HSV-TK system controlled tumour cell growth and achieves strong antitumour efficacy in vivo. These findings provide a foundation for the development of potential targeted clinical therapies for bladder cancer in humans. © Springer Science+Business Media, LLC 2011.

Zhang Z.,University of California at Irvine | Zhang Z.,Tianjin Medical University | Takarada S.,University of California at Irvine | Molloi S.,University of California at Irvine
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2012

Coronary flow reserve (CFR) and fractional flow reserve (FFR) are important physiological indexes for coronary disease. The purpose of this study was to validate the CFR and FFR measurement techniques using only angiographic image data. Fifteen swine were instrumented with an ultrasound flow probe on the left anterior descending artery (LAD). Microspheres were gradually injected into the LAD to create microvascular disruption. An occluder was used to produce stenosis. Contrast material injections were made into the left coronary artery during image acquisition. Volumetric blood flow from the flow probe (Q q) was continuously recorded. Angiography-based blood flow (Q a) was calculated by using a time-density curve based on the first-pass analysis technique. Flow probe-based CFR (CFR q) and angiography-based CFR (CFR a) were calculated as the ratio of hyper-emic to baseline flow using Q q and Q a, respectively. Relative angiographic FFR (relative FFR a) was calculated as the ratio of the normalized Q a in LAD to the left circumflex artery (LCX) during hyperemia. Flow probe-based FFR (FFR q) was measured from the ratio of hyperemic flow with and without disease. CFR a showed a strong correlation with the gold standard CFRq (CFR a = 0.91 CFR q + 0.30; r = 0.90; P < 0.0001). Relative FFR a correlated linearly with FFR q (relative FFR a = 0.86 FFR q + 0.05; r = 0.90; P < 0.0001). The quantification of CFR and relative FFR a using angiographic image data was validated in a swine model. This angiographic technique can potentially be used for coronary physiological assessment during routine cardiac catheterization. © 2012 the American Physiological Society.

Li X.S.,Tianjin Medical University
Zhonghua nan ke xue = National journal of andrology | Year: 2013

To study the etiology, clinical manifestation, diagnosis and treatment of giant prostatic calculus with neurogenic bladder disease and prostate diverticulum. We retrospectively analyzed the clinical data of a case of giant prostatic calculus with neurogenic bladder disease and prostate diverticulum and reviewed the relevant literature. The patient was a 37-year-old man, with urinary incontinence for 22 years and intermittent dysuria with frequent micturition for 9 years, aggravated in the past 3 months. He had received surgery for spina bifida and giant vesico-prostatic calculus. The results of preoperative routine urinary examination were as follows: WBC 17 -20/HPF, RBC 12 - 15/HPF. KUB, IVU and pelvic CT revealed spina bifida occulta, neurogenic bladder and giant prostatic calculus. The patient underwent TURP and transurethral lithotripsy with holmium-YAG laser. The prostatic calculus was carbonate apatite in composition. Urinary dynamic images at 2 weeks after surgery exhibited significant improvement in the highest urine flow rate and residual urine volume. Seventeen months of postoperative follow-up showed dramatically improved urinary incontinence and thicker urine stream. Prostate diverticulum with prostatic giant calculus is very rare, and neurogenic bladder may play a role in its etiology. Cystoscopy is an accurate screening method for its diagnosis. For the young patients and those who wish to retain sexual function, TURP combined with holmium laser lithotripsy can be employed, and intraoperative rectal examination should be taken to ensure complete removal of calculi.

Wu M.,University of South China | Chen S.-W.,University of South China | Jiang S.-Y.,Tianjin Medical University
Mediators of Inflammation | Year: 2015

An increase in the prevalence and severity of gingival inflammation during pregnancy has been reported since the 1960s. Though the etiology is not fully known, it is believed that increasing plasma sex steroid hormone levels during pregnancy have a dramatic effect on the periodontium. Current works of research have shown that estrogen and progesterone increasing during pregnancy are supposed to be responsible for gingivitis progression. This review is focused not only on epidemiological studies, but also on the effects of progesterone and estrogen on the change of subgingival microbiota and immunologic physiological mediators in periodontal tissue (gingiva and periodontal ligament), which provides current information about the effects of pregnancy on gingival inflammation. © 2015 Min Wu et al.

Hao Y.-B.,Xian Jiaotong University | Hao Y.-B.,Zhengzhou University | Yi S.-Y.,Zhengzhou University | Ruan J.,Tianjin Medical University | And 2 more authors.
Cancer Letters | Year: 2014

Chemotherapy is the mainstay of treatment in mid-advanced tumors. Considering their toxicity on hematopoietic cells, chemotherapeutics are often considered as immunosuppressive inducers. However, recently accumulating data indicate that some chemotherapeutic agents with specific administration schedules also display some positive immunological effect to contribute to tumor elimination. For instance, metronomic chemotherapy could promote tumor eradication not only by inhibiting tumor angiogenesis but also by selectively eliminating immunosuppressive cells and improving anti-tumor immune responses. In this review, we summarize what is currently known regarding metronomic chemotherapy-induced immunoregulation. Understanding of the molecular mechanisms of metronomic chemotherapy-induced immunoregulation may yield invaluable information for the optimal design of immunochemotherapies. © 2014 Elsevier Ireland Ltd. All rights reserved.

To explore the applications of blood oxygenation level dependent-functional magnetic resonance imaging (BOLD-fMRI), diffusion tensor imaging (DTI) and cortical somatosensory evoked potentials (Co-SEP), motor evoked potentials (MEP) and electrocorticogram (ECoG) in secondary epileptic surgery of primary motor area (M1). In 19 patients, preoperative BOLD-fMRI were performed to display the relationship between active zone, fiber bundle and epileptogenic lesions. Besides, Co-SEP, MEP and ECoG were also carried out intra-operatively to direct the resection of epileptogenic lesion and epileptogenic focus. At the same time, the nervous functions were protected as much as possible. Then fMRI was performed again to ensure that the post-operative nervous function was excellent. In preoperative BOLD-fMRI and DTI examinations, active zone and fiber bundle could be seen at the edge of lesions (n = 12); range reduced, become deformed or removed (n = 6); glioma epileptogenic lesion was close-up with M1 (n = 1). The central sulcus was confirmed by Co-SEP in all cases. And two cases were inconsistent with anatomical location; Stimulating precentral gyrus, MEP were elicited post-operatively from orbicularis oris, muscle of thenar, hypothenar muscle or flexor digitorum brevis. Under the monitoring of ECoG, spike-wave was monitored in all cases. Of these, epileptogenic focus was in M1 (n = 15). After treatment, spike-wave were reduced significantly or disappeared. At a post-operative follow-up of 6 - 12 months, seizure improvement has achieved Engel III level or above (n = 18). On re-examinations of BOLD-fMRI and DTI, active zone became bigger than before and fiber bundle was symmetric with opposite side. Two of 19 cases had transient motor aphasia incompletely or hemiparesis. No permanent neurological dysfunction occurred. There was no relapse in cases of glioma. BOLD-fMRI and Co-SEP, MEP and ECoG are complementary in M1 of secondary epilepsy surgery. It is effective to preserve nervous functions and enhance the quality of life for patients with epilepsy.

Yang F.,Peking University | Yang F.,China Astronaut Research and Training Center | Sun L.,Peking University | Li Q.,Peking University | And 5 more authors.
EMBO Journal | Year: 2012

SET8 is implicated in transcriptional regulation, heterochromatin formation, genomic stability, cell-cycle progression, and development. As such, it is predicted that SET8 might be involved in the development and progression of tumour. However, whether and how SET8 might be implicated in tumourigenesis is currently unknown. Here, we report that SET8 is physically associated with TWIST, a master regulator of epithelial-mesenchymal transition (EMT). We demonstrated that SET8 and TWIST are functionally interdependent in promoting EMT and enhancing the invasive potential of breast cancer cells in vitro and in vivo. We showed that SET8 acts as a dual epigenetic modifier on the promoters of the TWIST target genes E-cadherin and N-cadherin via its H4K20 monomethylation activity. Significantly, in breast carcinoma samples, SET8 expression is positively correlated with metastasis and the expression of TWIST and N-cadherin and negatively correlated with E-cadherin. Together, our experiments revealed a novel role for SET8 in tumour invasion and metastasis and provide a molecular mechanism underlying TWIST-promoted EMT, suggesting SET8 as a potential target for intervention of the metastasis of breast cancer. © 2012 European Molecular Biology Organization | All Rights Reserved.

Xu D.,Tianjin Medical University
Journal of neurosurgery | Year: 2010

The authors evaluated the results they obtained using Gamma Knife surgery (GKS) in patients with orbital tumors. This is a retrospective clinical evaluation of 202 patients with orbital tumors who were treated with GKS between September 1995 and October 2008. The series included 84 men and 118 women with a mean age of 39.5 ± 14.6 years (range 5-85 years). The diagnoses were determined based on pathological analyses in 113 patients and presumed based on characteristic clinical and imaging findings in 89 patients. There were 84 meningiomas, 38 epithelial tumors of the lacrimal gland, 23 schwannomas, 18 malignant choroidal melanomas, 12 optic nerve gliomas, 11 orbital metastases, 10 pseudotumors of the orbit, 3 retinoblastomas, and 3 cases of fibromatosis. The median target volume was 5.4 cm(3) (range 0.04-35.6 cm(3)). The tumor margin dose ranged from 10 to 40 Gy. At a median follow-up period of 34.5 ± 14.7 months (range 12-114 months), tumor shrinkage was observed in 118 patients (58.4%) and stable tumor size in 71 patients (35.1%). Regularly scheduled neuroimaging studies demonstrated evidence of tumor progression in only 13 patients (6.4%): 9 of these patients underwent repeated GKS and 4 received surgical treatment. Visual acuity was preserved in 129 patients. Seventy-two patients experienced some degree of improvement in vision. Severe deterioration of visual acuity was found in 18 of 147 patients who had useful vision before treatment. Nineteen patients (9.4%) experienced transient conjunctival edema; no other serious acute side effect was observed. Gamma Knife surgery provides an effective management strategy in patients with orbital tumors; it achieves excellent preservation of neurological function and is associated with few treatment-related complications.

Zhang T.,Tianjin Medical University
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2010

This study was purposed to investigate the immune state of T cells, the quantity and function of GPI(+) T cells and GPI(-) T cells in patients with paroxysmal nocturnal hemoglobinuria (PNH). 22 cases of PNH and 18 normal controls were enrolled in this study. Their T lymphocyte subsets, Th lymphocyte subsets were assayed by flow cytometry with the monoclonal antibodies concerned. The proportion of GPI(+) T cells or GPI(-) T cells in CD3(+) T cells, CD4(+) T cells, CD8(+) T cells and the expressions of CD69 on these T cells were also respectively assayed. The results showed that the proportion of CD4(+) T cells in CD3(+) T cells in PNH [(47.7670 +/- 13.91139)%] was lower than that in controls [(54.9592 +/- 7.11678)%] (p < 0.05). CD8(+) T cells in CD3(+) T cells of PNH cases [(52.2767 +/- 13.90395)%] were higher than that of controls [(45.2418 +/- 6.75306)%] (p < 0.05). The ratio of CD4(+) T cells to CD8(+) T cells was reverse in PNH. Those were more significantly in PNH-AA (0.77763 +/- 0.409153) (p < 0.05). The proportion of Th1 cells in PNH [(16.9136 +/- 6.78899)%], especially in PNH-AA [(22.8000 +/- 5.45244)%], was significantly higher than that in controls [(4.4600 +/- 1.81879)%] (p < 0.05). The proportion of Th2 cells in PNH [(4.7582 +/- 1.98441)%] had no difference from controls [(3.7960 +/- 1.13810)%]. The number of GPI(-) T cells in CD8(+) T cells and CD4(+) T cells were (14.6797 +/- 11.96718)% and (3.9241 +/- 2.46263)% respectively. The expression of CD69 on GPI(+) T cells or GPI(-) T cells in PNH [CD8(+) GPI(+) T cells (17.67881 +/- 8.562493)%, CD8(+) GPI(-) T cells (15.86575 +/- 7.279743)%, CD4(+) GPI(+) T cells (4.65431 +/- 1.984378)%, CD4(+) GPI(-) T cells (4.93181 +/- 1.730001)%]was significantly higher than that in normal controls [CD8(+) GPI(+) T cells (4.68038 +/- 1.216645)%, CD4(+) GPI(-) T cells (1.77339 +/- 0.645259)%] (p < 0.05), but the expression of CD69 on GPI(+) T cells was not different from that on GPI(-) T cells in PNH. It is concluded that high function of cytoimmunity in PNH may be responsible for bone marrow failure but not relates to the existence of PNH clone in T cell population.

Gao H.P.,Tianjin Medical University
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2013

To investigate the diagnosis and treatment of pancreatic islet cell tumors. Fifty-one patients with islet cell tumors treated in our department from January 1991 to April 2011 were included in this study. The data of clinical features, diagnosis and treatment were retrospectively analyzed. Among the 51 cases, 38 cases showed typical Whipple's triad, and the other 13 cases were non-functional islet cell tumors. In these 13 cases, 5 patients had no specific clinical symptoms, and 8 patients had abdominal distending pain. The positive rates of imaging were: B-ultrasound 43.1%, multi-slice spiral CT 69.8%; MRI 62.5%, endoscopic ultrasonography (EUS) 64.7% (11/17), and intraoperative ultrasound (IOUS) 96.3%, the differences among them were statistically significant (P<0.05). All patients underwent surgical treatment. Postoperative pancreatic leakage happened in 6 cases. Finally all the patients recovered after effective external drainage, anti-infection treatment and nutritional support. Intraoperative ultrasonography (IOUS) has a higher accuracy in the diagnosis of pancreatic islet cell tumors, compared with preoperative B-ultrasonography, CT, MRI, and endoscopic ultrasound (EUS). The most effective treatment of this disease is surgery.

Wang Y.,Tianjin Medical University | Nolan M.,University of Sheffield
Ageing and Society | Year: 2016

Decision-making among older patients with stroke, their families and professionals has been extensively studied in a Western context, but there has been little prior work in China. The study reported here explored how decision-making took place between older people with stroke, their family carers and professionals in an acute care context in mainland China using a constructivist grounded theory approach. Data were collected through semi-structured interviews, participant observation and documentary analysis. Constant comparative analysis of the data was carried out. This paper focuses on the key social process of 'hiding' and its dynamic relationship with the core category 'keeping the peace'. In order to meet the traditional Chinese cultural value of 'maintaining harmony', both family carers and professionals hid essential information from older stroke survivors who, as a consequence, were effectively precluded from playing an active role in major decisions. In understanding 'hiding', the paper draws upon both Chinese cultural values and 'awareness context theory' and in so doing questions the relevance to the Chinese context of key Western notions such as involvement in health-care decision-making. A better understanding of the experiences of decision-making processes between older people with stroke, their family carers and professionals in China will help professionals to provide the best possible support and care whilst promoting informed decision-making amongst all concerned. © 2015 Cambridge University Press.

Li C.Y.,Tianjin Medical University
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2010

To study the chemical constituents from Pachysandra terminalis and their antioxidant activity. Chemical constituents were isolated by repeated column chromatography (silica gel, Toyopearl HW-40C and preparative HPLC). The structures of isolated compounds were elucidated on the basis of spectral data analysis. DPPH method was used to evaluate the free radical scavenging activity of the isolated compounds. Six compounds were isolated and their structures were identified as follow: 2-Phenylethyl-beta-D-glucopyranoside (1), (+)Pinoresinol-4'-O-beta-D-glucopyranoside (2), Pinoresinol (3), cis-Syringin (4), 4-hydroxy-4-(3-oxo-l-butenyl)-3,5,5-trimethylcyclohex-2-en-l-one (5), 3alpha-hydroxy-5,6-epoxy-7-megastigmen-9-one (6). Compounds 2, 4, 5 showed obviously antioxidant activity, their DPPH free radical scavenging rates were 82.50%, 87.36%, and 84.56% on the concentration of 50 micromol/L, respectively. Compounds 1-6 are isolated from this genus for the first time. Compounds 2, 4, and 5 showed significant antioxidant activities.

Bai W.,Tianjin Medical University
Neuroscience bulletin | Year: 2012

Working memory is a key cognitive function in which the prefrontal cortex plays a crucial role. This study aimed to show the firing patterns of a neuronal population in the prefrontal cortex of the rat in a working memory task and to explore how a neuronal ensemble encodes a working memory event. Sprague-Dawley rats were trained in a Y-maze until they reached an 80% correct rate in a working memory task. Then a 16-channel microelectrode array was implanted in the prefrontal cortex. After recovery, neuronal population activity was recorded during the task, using the Cerebus data-acquisition system. Spatio-temporal trains of action potentials were obtained from the original neuronal population signals. During the Y-maze working memory task, some neurons showed significantly increased firing rates and evident neuronal ensemble activity. Moreover, the anticipatory activity was associated with the delayed alternate choice of the upcoming movement. In correct trials, the averaged pre-event firing rate (10.86 ± 1.82 spikes/bin) was higher than the post-event rate (8.17 ± 1.15 spikes/bin) (P<0.05). However, in incorrect trials, the rates did not differ. The results indicate that the anticipatory activity of a neuronal ensemble in the prefrontal cortex may play a role in encoding working memory events.

Zhao L.,Tianjin Medical University
World Chinese Journal of Digestology | Year: 2015

AIM: To investigate the effect of improvement of nutritional diet on the digestive system of intensive care unit (ICU) patients. METHODS: One hundred and twentys ix ICU pat ient s t reated f rom January and December 2014 at our hospital were randomly divided into an observat ion group and a control group, with 63 cases in each group. All cases received early enteral nutrition through a nasogastric tube. Nutrition was used in the control group, while an improved nutritional diet, which mixed Sanku compound nutrition and protein nutrition at 2∶1, was used in the observation group. The incidences of gastrointestinal complications such as diarrhea, constipation, and gastric retention, score of gastrointestinal function and patient’s satisfaction were compared between the two groups. RESULTS: The incidences of diarrhea, constipation, and gastric retention after nasal feeding in the observation group were significantly lower than those in the control group (P < 0.05). The scores of gastrointestinal function on 3 and 7 d after nasal feeding in the observation group were significantly lower than those in the control group (P < 0.05). The patients’ satisfaction and total satisfaction rate in the observation group were significantly better than those in the control group (P < 0.05). CONCLUSION: Nutritional diet improvement in ICU patients could significantly reduce the risk of gastrointestinal dysfunction, promote the recovery of digestive system function, and improve the patients’ satisfaction. © 2015 Baishideng Publishing Group Inc. All rights reserved.

Ma X.-L.,Tianjin Hospital | Sun X.-L.,Tianjin Hospital | Wan C.-Y.,Tianjin Hospital | Ma J.-X.,Tianjin Medical University | Tian P.,Tianjin Hospital
Journal of Orthopaedic Research | Year: 2012

Fracture healing is a complex bone formation process, and neovascularization may contribute to new bone regeneration. The circulating endothelial progenitor cell (EPC) mobilization and homing could involve in neovascularization and vasculogenesis. In this study, we investigate the changes of circulating EPC during bone fracture healing, and the possible contribution of EPCs to increased neovascularization and fracture healing. The number of circulating EPCs was monitored in twenty-four patients with long bone traumatic fracture within the first 48 h and at 3, 5, 10, and 14 days post-fracture. The mononuclear cells which isolated from peripheral blood were analyzed by flow cytometry. Peripheral blood counts of leukocytes and platelets were measured by hematology analyzer. The amount of peripheral EPCs significantly increased in patients with fracture compared to age-matched healthy control subjects within the first 48 h after injury, and peaked at 3 days post-fracture. There was no significant difference in the change trend of early EPCs between male and female, but the number of early EPCs was significantly greater in younger patients compared to older patients. A comparison of the EPCs levels between patients with severe injury (ISS > 16) and patients with mild injury (ISS ≤ 16) revealed no statistically significant difference. The level of early EPCs was inverse correlation with the level of plate after fracture, but no correlation with the level of peripheral leucocytes. These findings suggest traumatic fracture may induce the mobilization of EPCs into the peripheral circulation. The increased EPCs may contribute to neovascularization and involve in fracture healing. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1860-1866, 2012.

Walsh A.S.,University of Oxford | Yin H.,Tianjin Medical University | Yin H.,University of Oxford | Erben C.M.,University of Oxford | And 2 more authors.
ACS Nano | Year: 2011

DNA cages are nanometer-scale polyhedral structures formed by self-assembly from synthetic DNA oligonucleotides. Potential applications include in vivo imaging and the targeted delivery of macromolecules into living cells. We report an investigation of the ability of a model cage, a DNA tetrahedron, to enter live cultured mammalian cells. Cultured human embryonic kidney cells were treated with a range of fluorescently labeled DNA tetrahedra and subsequently examined using confocal microscopy and flow cytometry. Substantial uptake of tetrahedra into cells was observed both when the cells were treated with tetrahedra alone and when the cells were treated with a mixture of tetrahedra and a transfection reagent. Analysis of the subcellular localization of transfected tetrahedra using confocal microscopy and organelle staining indicates that the cages are located in the cytoplasm. FRET experiments indicate that the DNA cages remain substantially intact within the cells for at least 48 h after transfection. This is a first step toward the use of engineered DNA nanostructures to deliver and control the activity of cargoes within cells. © 2011 American Chemical Society.

Wang X.,Tianjin Medical University | Zhang Z.,Dalian Central Hospital | Yao C.,Jilin University
Cancer Investigation | Year: 2011

The pathophysiology of multiple myeloma-induced angiogenesis is complex and involves both direct production of angiogenic cytokines by plasma cells and their induction within the microenvironment. In this research, we investigated whether mesenchymal stem cells participated in inducing the angiogenic response in multiple myeloma, and explored the mechanism by which MSCs influence myeloma angiogenesis. We detected the concentration of angiogenic factors (bFGF, HGF, and VEGF) in the conditioned medium of mesenchymal stem cells and the capillary formation ability of mesenchymal stem cells in vitro. We found that conditioned medium of MSCs derived from MM significantly promoted the proliferation, chemotaxis, and capillary formation of human umbilical vein endothelial cells compared with that from normal donors. ELISA and RT-PCR were used to detect the mRNA and protein levels of angiogenic factors (bFGF, HGF, and VEGF) in the conditioned medium. We found that mRNA and protein levels of angiogenic factors were elevated in MSCs from multiple myeloma compared with normal donors. © 2011 Informa Healthcare USA, Inc.

Fang L.,Nanchang Hangkong University | Wang Y.,Tianjin Medical University | He X.,Nanchang Hangkong University
Journal of Cataract and Refractive Surgery | Year: 2013

Purpose: To analyze the induced wavefront aberrations caused by treatment decentration and transition zone after custom myopic laser refractive surgery. Setting: Refractive Surgery Center, Tianjin Eye Hospital & Eye Institute, Tianjin Medical University, Tianjin, China. Design: Cohort study. Methods: Wavefront aberration data from potential refractive surgery candidates were used. Based on the preoperative wavefront aberrations, the custom ablation profile was computed. Then, the influence of treatment decentration and especially that of the transition zone on induced wavefront aberrations was studied. The impact of angle mismatch on induced aberrations was analyzed. Results: Data from 117 eyes (77 patients) were analyzed. The transition zone played a significant role in the influence of decentration on the induced aberrations in refractive surgery. Induced coma and spherical aberration increased rapidly as the lateral translation increased, and coma was significantly larger than other Zernike aberration terms. The induced aberrations from decentration with oblique incidence in the laser ablation profile were less than in the actual laser ablation process for slight subclinical decentration. The induced aberrations were not closely related to the subclinical unmatched angle from eye cyclotorsion. The induced aberrations from lateral translation were correlated with the position vector. The transition zone was designed to smooth the transition from the optical zone to the untreated cornea, and it mainly dominated induced coma and spherical aberration. Conclusion: To achieve the best postoperative visual performance, the effect of the transition zone in refractive surgery should be taken into account, especially for scotopic pupils. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. © 2013 ASCRS and ESCRS Published by Elsevier Inc.

Sidoli S.,University of Southern Denmark | Schwammle V.,University of Southern Denmark | Ruminowicz C.,University of Southern Denmark | Hansen T.A.,University of Southern Denmark | And 5 more authors.
Proteomics | Year: 2014

We present an integrated middle-down proteomics platform for sensitive mapping and quantification of coexisting PTMs in large polypeptides (5-7 kDa).We combined an RP trap column with subsequent weak cation exchange-hydrophilic interaction LC interfaced directly to high mass accuracy ESI MS/MS using electron transfer dissociation. This enabled automated and efficient separation and sequencing of hypermodified histone N-terminal tails for unambiguous localization of combinatorial PTMs. We present Histone Coder and IsoScale software to extract, filter, and analyze MS/MS data, including quantification of cofragmenting isobaric polypeptide species. We characterized histone tails derived from murine embryonic stem cells knockout in suppressor of zeste12 (Suz12-/-) and quantified 256 combinatorial histone marks in histones H3, H4, and H2A. Furthermore, a total of 713 different combinatorial histone marks were identified in purified histone H3.Wemeasured a seven-fold reduction ofH3K27me2/me3 (where me2 and me3 are dimethylation and trimethylation, respectively) in Suz12-/- cells and detected significant changes of the relative abundance of 16 other single PTMs of histone H3 and other combinatorial marks. We conclude that the inactivation of Suz12 is associated with changes in the abundance of not only H3K27 methylation but also multiple other PTMs in histone H3 tails. © 2014 WILEY-VCH Verlag GmbH & Co.

Jing L.,Tianjin Medical University | Qiu Y.,State University of New York at Buffalo | Zhang Y.,Research Triangle Institute | Li J.-X.,State University of New York at Buffalo
Drug and Alcohol Dependence | Year: 2014

Background: Cannabinoid CB1 receptors play an essential role in drug addiction. Given the side effect profiles of orthosteric CB1 antagonism, new strategies have been attempted to modulate this target, such as CB1 receptor allosteric modulation. However, the effect of CB1 allosteric modulation in drug addiction is unknown. The present study examined the effects of the CB1 receptor allosteric modulator ORG27569 on the reinstatement of cocaine- and methamphetamine-seeking behavior in rats. Methods: Rats were trained to self-administer 0.75 mg/kg cocaine or 0.05 mg/kg methamphetamine in 2-h daily sessions for 14 days which was followed by 7 days of extinction sessions in which rats responded on the levers with no programmed consequences. On reinstatement test sessions, rats were administered ORG27569 (1.0, 3.2, 5.6 mg/kg, i.p.) or SR141716A (3.2 mg/kg, i.p.) 10 min prior to re-exposure to cocaine- or methamphetamine-paired cues or a priming injection of cocaine (10 mg/kg, i.p.) or methamphetamine (1 mg/kg, i.p.). Results: Both cues and a priming injection of cocaine or methamphetamine significantly reinstated the extinguished active lever responding. Pretreatment with ORG27569 resulted in a dose-related attenuation of both cue- and drug-induced reinstatement of cocaine- and methamphetamine-seeking behavior. SR141716A also exhibited similar inhibitory action on reinstatement of drug-seeking behavior. Conclusion: Negative allosteric modulation of CB1 receptors can produce similar functional antagonism as orthosteric CB1 receptor antagonists on reinstatement of drug-seeking behavior. Thus, ORG27569 or other negative allosteric modulators deserve further study as potentially effective pharmacotherapy for drug addiction. © 2014 Elsevier Ireland Ltd. All rights reserved.

Yan H.,Tianjin Medical University
Chinese Journal of Ophthalmology | Year: 2015

Management of ocular trauma is widely carried out in China presently. Quick development of treatment and research of ocular trauma was achieved in the last five years, and the achievement was inspired. However, we expressly see that there are still a lot of further work to do in the field of epidemiology of ocular trauma, criterions and guidelines for ocular trauma treatment, meticulous treatment of ocular trauma and technique innovation, and research of ocular trauma. The level of prevention and treatment of ocular trauma should be increased stably so long as the direction is right and the performance is earnest. Meanwhile, the academic status and impact of Chinese ocular trauma field can be elevated in the world consequently. Copyright © 2015 by the Chinese Medical Association.

Zhu H.-J.,Tianjin University | Liu J.-H.,Tianjin University | Sun L.-F.,Tianjin Medical University | Hu Z.-F.,Tianjin University | Qiao J.-J.,Tianjin University
Bioresource Technology | Year: 2013

Spent mushroom substrate (SMS) was pretreated with alkaline reagents including potassium hydroxide, lime and ammonia to enhance enzymatic saccharification. Under the best pretreatment conditions (1M KOH, 80°C, 90min; 1M lime, 80°C, 120min; 10M ammonia, 70°C, 120min), the total reducing sugar (TRS) yield reached 258.6, 204.2 and 251.2mg/g raw SMS, which were respectively 6.15, 4.86, and 5.98times of untreated SMS. The effects of pretreatment by above alkaline reagents and sulfuric acid on the composition and structure of SMS were evaluated to provide comparative performance data. A new process, combined alkali and acid (CAA) pretreatment followed by enzymatic hydrolysis, was innovatively proposed to improve the cost-effectiveness and avoid environmental problems. The SMS residue after CAA pretreatment-enzymatic hydrolysis process was converted to biofertilizer with Pichia farinose FL7 and a cell density of 3.0×108cfu/g in biomass was attained. © 2013 Elsevier Ltd.

Ma X.,Tianjin 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 investigate the differences in biomechanical properties between fresh and chemically extracted acellular peripheral nerve. Thirty-six sciatic nerves were harvested from 18 adult male Wistar rats of 3 months old and randomly assigned into 3 groups (n = 12 per group): normal control group (group A), the nerve segments received no treatment; Sondell method group (group B), the nerve segments were chemically extracted with the detergents of Triton X-100 and sodium deoxycholate; and improved method group (group C), chemically extracted acellular treatment of nerve was done with the detergents of Triton X-200, Sulfobetaine-10 (SB-10), and SB-16. After the acellularization, the structural changes of nerves in each group were observed by HE staining and field emission scanning electron microscope, then the biomechanical properties of nerves were tested using mechanical apparatus (Endura TEC ELF 3200). HE staining and field emission scanning electron microscope showed that the effect of acellularization of group C was similar to that of group B, but the effects of demyelination and integrity of nerve fiber tube of group C were better than those of group B; the structure of broken nerves was more chaotic than before biomechanical test. The biomechanical test showed that the ultimate load, ultimate stress, ultimate strain, mechanical work to fracture in group A were the largest, the next was group C, the least was group B; the tenacity and elastic modulus in group C were the largest, the next was group B, the least was group A; but the differences were not significant (P > 0.05). Compared with Sondell method, the nerve treated by improved method is more appropriate for use in vivo.

Zhao R.,Tianjin 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 study the effect of chitosan (CS) mediated insulin-like growth factor 1 gene (igf-1) transfection on the repair of articular cartilage defect. Twelve 3-month-old healthy male rabbits weighting 2.0-2.5 kg were randomly divided into 2 primary groups, control and intervention groups (n = 6 per group). Control group was further divided into normal control (left knee) and normal saline (NS) control (right knee) groups. While, intervention group was divided into CS (left knee) and CS/igf-1 intervention (right knee) groups. Cartilage defects were created in the knee joints except normal control. Intra-articular injections of CS/igf-1 complex was administrated 2 times a week for 4 weeks in CS/igf-1 intervention group, 0.5 mL CS in CS intervention group, and 0.5 mL saline solution in normal control and saline control groups. At 28 days after treatments, the cartilage samples were collected for histological observation and collagen type II and aggrecan mRNA evaluation. HE staining and toluidine blue staining revealed that CS/igf-1 and CS intervention could significantly stimulated cartilage regeneration accompanied with fibrosis and inflammatory cell infiltration, however, CS/igf-1 treatment resulted in the best repair of cartilage defect. In contrast, saline control group only showed fibrous tissue proliferation and inflammatory cell infiltration without significant cartilage repairing. In terms of collagen type II and aggrecan gene expression, significant differences were observed in each pairwised comparison among 4 groups in the order of CS/igf-1 > CS > NS > normal control (P < 0.05). In situ CS/ifg-1 complex transfection can enhance the formation of mesochondrium by upregulating collagen type II or aggrecan expression, which might enhance the repair of articular cartilage defect.

The authors sought to evaluate modification of the radiation response of C6 glioma cells in vitro and in vivo by inhibiting the expression of Ku70. To do so they investigated the effect of gene transfer involving a recombinant replication-defective adenovirus containing Ku70 short hairpin RNA (Ad-Ku70shRNA) combined with Gamma Knife treatment (GKT). First, Ad-Ku70shRNA was transfected into C6 glioma cells and the expression of Ku70 was measured using Western blot analysis. In vitro, phenotypical changes in C6 cells, including proliferation, cell cycle modification, invasion ability, and apoptosis were evaluated using the MTT (3'(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) assay, Western blot analysis, and cell flow cytometry. In vivo, parental C6 cells transfected with Ad-Ku70shRNA were implanted stereotactically into the right caudate nucleus in Sprague-Dawley rats. After GKS, apoptosis was analyzed using the TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) method. The inhibitory effects on growth and invasion that were induced by expression of proliferating cell nuclear antigen and matrix metalloproteinase-9 were determined using immunohistochemical analyses. The expression of Ku70 was clearly inhibited in C6 cells after transfection with Ad-Ku70shRNA. In vitro following transfection, the C6 cells showed improved responses to GKT, including suppression of proliferation and invasion as well as an increased apoptosis index. In vivo following transfection of Ad-Ku70shRNA, the therapeutic efficacy of GKT in rats with C6 gliomas was greatly enhanced and survival times in these animals were prolonged. Our data support the potential for downregulation of Ku70 expression in enhancing the radiosensitivity of gliomas. The findings of our study indicate that targeted gene therapy-mediated inactivation of Ku70 may represent a promising strategy in improving the radioresponsiveness of gliomas to GKT.

Zheng R.,Tianjin Medical University | Shu S.,Providence Cancer Center
Journal of Surgical Oncology | Year: 2011

Regional draining lymph nodes (LNs) play a pivotal role in initiating immune responses. However, the presence of metastases may compromise their normal immunological function. Preclinical studies indicate that despite metastases, early tumor-draining LNs are still a rich source of sensitized T cells. Recently, we found that dendritic (DC)-tumor fusion hybrids were capable of stimulating therapeutic T-cell generation in the LN. However, this response is regulated by a tumor-specific suppression mechanism(s). Reversal of these dysfunctions would help the success of immunotherapy. Copyright © 2011 Wiley-Liss, Inc.

Xiong S.,University of Texas M. D. Anderson Cancer Center | Mu T.,Dalian Medical University | Wang G.,Tianjin Medical University | Jiang X.,Sloan Kettering Cancer Center
Protein and Cell | Year: 2014

The mitochondria-mediated caspase activation pathway is a major apoptotic pathway characterized by mitochondrial outer membrane permeabilization (MOMP) and subsequent release of cytochrome c into the cytoplasm to activate caspases. MOMP is regulated by the Bcl-2 family of proteins. This pathway plays important roles not only in normal development, maintenance of tissue homeostasis and the regulation of immune system, but also in human diseases such as immune disorders, neurodegeneration and cancer. In the past decades the molecular basis of this pathway and the regulatory mechanism have been comprehensively studied, yet a great deal of new evidence indicates that cytochrome c release from mitochondria does not always lead to irreversible cell death, and that caspase activation can also have non-death functions. Thus, many unsolved questions and new challenges are still remaining. Furthermore, the dysfunction of this pathway involved in cancer development is obvious, and targeting the pathway as a therapeutic strategy has been extensively explored, but the efficacy of the targeted therapies is still under development. In this review we will discuss the mitochondria-mediated apoptosis pathway and its physiological roles and therapeutic implications. © 2014, The Author(s).

Yu M.,University of Ottawa | Wan Y.,Tianjin Medical University | Zou Q.,China National Petroleum Corporation
Clinica Chimica Acta | Year: 2010

Background: Somatic mutations and germline variations in mitochondrial DNA (mtDNA) have been widely detected in a range of human malignancies including Ewing's sarcoma (EWS). However, it still remains unknown whether quantitative alterations in mtDNA level occur during the initiation and/or progression of EWS. Methods: To test this possibility, we determined mtDNA copy number from 17 cases of EWS tumor tissues and 5 normal bone tissue samples using a quantitative real-time PCR assay. Results: Our results showed that the average mtDNA content was significantly reduced in cancerous specimens as compared to that in normal bone controls. mtDNA copy number was statistically associated with tumor metastasis. There was an over 2-fold decrease in tumors with metastasis than in low-grade ones without metastasis. In addition, change in mtDNA content was related to somatic mutations in the D-loop control region. Tumors harboring D-loop mutations, at the polycytidine stretch between nucleotide positions 303 and 309 or close to the replication origin sites of the heavy strand, exhibited significantly lowered mtDNA levels in comparison with those without D-loop alterations. Conclusions: The mtDNA content reduction may be an important genetic event in the carcinogenesis of EWS. This study provides evidence that somatic D-loop mutation is likely one of the key factors contributing to quantitative changes of mtDNA in EWS. © 2010 Elsevier B.V.

To observe the serum concentration and evaluate clinical efficacy of piperacillin/tazobactam (TZP) prolonged infusion time in treatment of hospital acquired pneumonia (HAP). Fifty HAP patients admitted to intensive care unit (ICU) from March 1 to October 31, 2012 were enrolled. The bacterial drug sensitivity results showed that the minimum inhibitory concentration (MIC) of TZP was 8 mg/L or 16 mg/L. According to completely randomized grouping method, the patients were divided into treatment group (n=25) and control group (n=25). The therapeutic regimen in control group was TZP 4.5 g, in regular infusion every 6 hours and finished in 30 minutes; the treatment group was TZP 4.5 g, in prolonged infusion every 6 hours by using infusion pump for continuous intravenous infusion 3 hours. Acute physiology and chronic health evaluation II(APACHEII) score, clinical pulmonary infection score (CPIS) and procalcitonin (PCT) level were compared between the two groups 3 days after treatment. The treatment success rate, remedial treatment rate, antibiotic costs were recorded in both groups. Blood specimen was collected at 0.5, 1, 2, 3, 4, 6 hours at the beginning of administration, and the blood drug concentration of piperacillin and tazobactam was determined using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The PCT (2.16±0.17 μg/L vs. 4.77±0.25 μg/L), CPIS score(6.21±1.14 μg/L vs. 6.92±1.35 μg/L) and remedial treatment rate (12.0% vs. 52.0%) of the treatment group were significantly lower than those of the control group after administration for 3 days (P<0.05 or P<0.01), and APACHEII score was slightly lower than that in control group (21.38±7.37 vs. 22.15±5.46, P>0.05). After active remedial treatment, there were no significant difference in the treatment success rate (88.0% vs. 80.0%) and relapse rate (4.2% vs. 7.7%) between treatment group and control group (both P>0.05). But the antibiotic costs in treatment group were significantly lower than that of control group (4330.38±1087.24 Yuan vs. 5506.15±1361.73 Yuan, P<0.01). The treatment course of antibacterials in treatment group was significantly shorter than that in control group (6.00±1.05 days vs. 8.20±1.03 days, P<0.01). The infection by Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae was monitored, TZP serum concentration administrated at 0.5-6 hours in the treatment group was higher than MIC, but in the control group, TZP blood concentration was lower than MIC after administration for 2-3 hours. In treatment group, the percentage of duration of blood drug level higher than MIC account for dosing interval (%T>MIC) was 86.82%, while in the control group, the %T>MIC was 42.84%. TZP prolonged the infusion time dosing regimens using in Gram negative bacteria induced by high MIC value of HAP have more stable plasma concentration, curative clinical effect and reduce the cost of treatment.

RESULTS: Cell cycle analyses and transwell assays showed that p21 inhibited the proliferation and migration of RPE cells. Increased expression of p21 was detected in cultured RPE cells and rabbit retinas after transfection with the p21 gene, whereas levels of CDK2 and cyclinE were decreased. The increase in p21 expression effectively suppressed the development of PVR in a rabbit model.CONCLUSIONS: The increase in p21 expression in RPE cells not only inhibits the proliferation and migration of RPE cells in vitro, but also suppresses the development of PVR in vivo, which indicates its therapeutic potential in treating PVR.METHODS: Cell cycle analyses and transwell assays were conducted to assess cell proliferation characteristics and the migration ability of RPE cells after transfection with p21. Western blot and reverse-transcription polymerase chain reaction technologies were used to detect the expression of p21, CDK2 and cyclinE in RPE cells and rabbit retinal tissues. The impact of increasing p21 expression on PVR development was conducted by implantation of an adenovirus vector containing rabbit p21 (rAd-p21) in a PVR rabbit model. The prevalence of PVR and retinal detachment was determined by indirect ophthalmoscopy on days 3, 7, 14, and 21 after the injection of rAd-p21 into the vitreous. B scans and hematoxylin-eosin staining were employed to check rabbit retinas on day 21.BACKGROUND: P21 is one kind of cyclin-dependent kinase inhibitor that can prevent cells from going through the G1/S phase checkpoint and inhibit cell proliferation. Proliferative vitreoretinopathy (PVR) is a proliferative response in the eye. The aim of this study was to determine whether p21Waf1/Cip1 (p21) suppresses the proliferation and migration of retinal pigment epithelial (RPE) cells in vitro and controls PVR development in vivo.

We investigated the effects of telmisartan, the blocker of angiotensin II receptor 1, on the regulation of systolic blood pressure (SBP) and oxidative stress through endothelial nitric oxide (NO) release in spontaneously hypertensive rats (SHRs). SHRs randomly received placebo, oral feeding of telmisartan (5 mg/kg or 10 mg/kg) every day and Wistar-Kyoto rats (WKYs) served as normotensive control. The SBP of rat was measured before and weekly thereafter. After a total of 8-week treatment, rats were killed for experimental measurements. Parameters that subject to measurements in isolated aorta endothelial cells include: NO concentration, protein expression levels of angiotensin II receptor 1, nitrotyrosine, 8-isoprostane, SOD, PI3K, Akt, AMPK and eNOS. In addition, L-NMMA, a general inhibitor of nitric oxide synthase, was also applied to test the inhibition of NO concentration. We found that SBPs were significantly lower in telmisartan therapy group than in placebo treated hypertensive rats and WKYs (p<0.05). The NO concentration was significantly higher in telmisartan-treated group with increased activity of the PI3K/Akt pathway and activated eNOS signaling. Blockade of Akt activity reversed such effects. Activation of AMPK also contributed to the phosphorylation of eNOS. L-NMMA treatment reduced less NO concentration in SHR rats than the telmisartan co-treated groups. Oxidative stress in SHRs was also attenuated by telmisartan administration, shown by reduced formation of nitrotyrosine, 8-isoprostane, and recovered SOD protein level. Telmisartan enhanced NO release by activating the PI3K/Akt system, AMPK phosphorylation and eNOS expression, which attenuated the blood pressure and oxidative stress in SHRs. © 2013 Institute of Physiology v.v.i., Academy of Sciences of the Czech Republic, Prague, Czech Republic.

Zhuang S.-M.,Tianjin Medical University | Chen F.,Tianjin An Kang Psychiatric Hospital
Nursing Research | Year: 2016

Background: Methamphetamine is a commonly used illicit drug that threatens many adolescents and youth in Asian Pacific countries, contributing to the heavy burden of disease and drug-related death. Little is known about the prevalence of associated psychological problems in methamphetamine-dependent adolescents and youth. Purpose: The study sought to estimate the prevalence of psychological problems in adolescents and youth in China with methamphetamine dependence and to identify factors related to co-occurring psychological problems. Methods: A cross-sectional design was used. Methamphetamine-dependent adolescents and youth fromtwo drug rehabilitation centers in Tianjin, China, took part. Each participant was assessed with a sociodemographic questionnaire and Symptom Checklist-90 (SCL-90). Results: A total of 161 adolescents and youth took part. Psychological symptomatology was high, with 59.6% of participants having over 160 points on the SCL-90 total score, indicating significant psychological distress. On the basis of subscale scores, phobic anxiety, depression, and anxiety were common. Male participants, younger adolescents, and those who are addicted to methamphetamine for a longer time with more consumption were more likely to experience psychological problems. Discussion: Nurses should be aware of the type and severity of psychological problems among methamphetamine-dependent adolescents and youth. Nursing care should be designed to relieve psychological problems and improve mental health of the methamphetamine-dependent adolescents and youth. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

BACKGROUND: The small bowel is one of the critical organs involved in gastrointestinal complications in cervical cancer treated with postoperative intensity modulated radiotherapy. Even with modest doses of radiation therapy (45-50Gy), the risk of severe injury from postoperative radiation therapy is between 5% and 15%. Up to now, a predictive model of acute GI complications of the small bowel has been established with the aid of Quantitative Analyses of Normal Tissue Effects in the Clinic. However, the correlation between dose-volume effect and chronic GI complications of the small bowel has not been extensively investigated. In the article, the correlation has been studied preliminarily.METHODS: This study analyzed 84 patients who underwent postoperative IMRT. The organ at risk that was contoured was the small bowel loops. DVH parameters subjected to analysis included maximum and mean dose, the volume of these organs receiving more than 30, 40, and 50 Gy (V30-50 volume) and the volume of V30-50 to total volume (V30-50 ratio). Association between DVH parameters or clinical factors and the incidence of grade 1-2 chronic GI complications were evaluated.RESULTS: Body position and RT total dose are significantly associated with grade 1-2 chronic GI complications after postoperative IMRT in early-stage cervical cancer patients. Maximum dose and V40 ratio of the small bowel loops were significantly associated with chronic GI complications (P < 0.05). The optimal threshold were 5586 cGy (maximum dose) and 28% (V40 ratio) of the small bowel loops.CONCLUSIONS: Maximum dose and V40 ratio of the small bowel loops should be considered synthetically before postoperative IMRT for early-stage cervical cancer.

Lin X.,Nanjing Southeast University | Lin X.,State Key Laboratory of Bioelectronics | Li Y.,Tianjin Medical University | Gu N.,Nanjing Southeast University | Gu N.,State Key Laboratory of Bioelectronics
Soft Matter | Year: 2011

We have performed coarse grained molecular dynamics simulations (CGMD) to investigate the interactions of generation 7, 5 and 3 (G7, G5 and G3) charge-neutral polyamidoamine (PAMAM) dendrimers with a DPPC (dipalmitoylphosphatidylcholine) monolayer at the air-water interface (model pulmonary surfactant) during the end-expiration process. Our results show that different generations of PAMAM dendrimers have different influences on the DPPC monolayer. Generally, G3 PAMAM dendrimers show little influence on the DPPC monolayer's structure and relative properties. While G7 and G5 PAMAM dendrimers tend to induce the formation of largely deformed structures of the DPPC monolayer and inhibit or even reverse the normal phase transition of the interfacial DPPC molecules during the process of compression. Besides, we find that the formation processes of these disrupted structures are energy-favorable based on analyzing van der Waals interaction energy between PAMAM dendrimers and the whole system. © The Royal Society of Chemistry 2011.

Li M.,Temple University | Yu D.,Tianjin Medical University | Jon Williams K.,Temple University | Liu M.-L.,Temple University
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2010

Objective: To investigate whether exposure of human monocytes/macrophages to tobacco smoke induces their release of membrane microvesicles (MVs) that carry tissue factor (TF) released from cells, whether smoke-induced MVs are procoagulant, and what cellular processes might be responsible for their production. Methods and Results: We found that exposure of human THP-1 monocytes and primary human monocyte-derived macrophages to 3.75% tobacco smoke extract (TSE) significantly increased their total and TF-positive MV generation. More importantly, MVs released from TSE-treated human monocytes/macrophages exhibited 3 to 4 times the procoagulant activity of control MVs, as assessed by TF-dependent generation of factor Xa. Exposure to TSE increased TF mRNA and protein expression and cell surface TF display by both THP-1 monocytes and primary human monocyte-derived macrophages. In addition, TSE exposure caused activation of C-Jun-N-terminal kinase (JNK), p38, extracellular signal regulated kinase (ERK) mitogen-activated protein kinases (MAPK), and apoptosis (a major mechanism for MV generation). Treatment of THP-1 cells with inhibitors of ERK, MAP kinase kinase (MEK), Ras, or caspase 3, but not p38 or JNK, significantly blunted TSE-induced apoptosis and MV generation. Surprisingly, neither ERK nor caspase 3 inhibition altered the induction of cell surface TF display by TSE, indicating an effect solely on MV release. Inhibition of ERK or caspase 3 essentially abolished TSE-induced generation of procoagulant MVs from THP-1 monocytes. Conclusion: Tobacco smoke exposure of human monocytes/macrophages induces cell surface TF display, apoptosis, and ERK-and caspase 3-dependent generation of biologically active procoagulant MVs. These processes may be novel contributors to the pathological hypercoagulability of active and secondhand smokers. © 2010 American Heart Association, Inc.

Yang J.,Tianjin Medical University | Zhang W.,University of Houston
Current Opinion in Oncology | Year: 2013

PURPOSE OF REVIEW: Recent translational studies in osteosarcoma are discussed with the purpose to shed light on the new molecular therapeutic targets. RECENT FINDINGS: The genetic aberrations of vascular endothelial growth factor (VEGF), mammalian target of rapamycin, Wnt signaling pathway, the inactivation of p53, Rb, WWOX genes, and amplification of APEX1, c-myc, RECQL4, RPL8, MDM2, VEGFA might be involved in the pathogenesis of osteosarcoma. The promising therapeutic targets for osteosarcoma patients include: integrin, ezrin, statin, NOTCH/HES1, matrix metalloproteinases (MMPs), m-calpain, and Src, which are involved in tumor cell invasion and metastasis; aldolase A, fructose-bisphosphate, sulfotransferase family 3A, member 1, BCL2-associated athanogene 3, heat shock protein 70 (HSP70), B-cell lymphoma 2-interacting mediator (BIM), polo-like kinase 1, hypoxia inducible factor 1, alpha subunit, minibrain-related kinase, Bcl-xl, caspase-3, midkine, high mobility group box 1 protein (HMGB1), and Beclin1, which are involved in tumor proliferation and apoptosis; met proto-oncogene (hepatocyte growth factor receptor), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, insulin-like growth factor (IGF)-1R, fms-related tyrosine kinase 4, platelet-derived growth factor receptor, beta polypeptide, IGF-I/II, and c-kit, which are involved in tumor growth; endosialin, VEGF, thrombin, and MMPs, which are involved in tumor angiogenesis; transforming growth factor-α/β, parathyroid hormone-like hormone, interleukin-6, interleukin-11, receptor activator of nuclear factor-κB ligand, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1, and cathepsin, which are involved in osteoclast function; Myc, HSP90, p-Met, p-Akt, p-STAT3, and cyclin D1, which are transcriptional factors; p-GP, hydroxysteroid (17-beta) dehydrogenase 10, HMGB1, BIM, inorganic phosphate, Bcl-2, PARP, mdm2, p21, Bax, and mitogen-activated protein kinase 1, which are involved in drug sensitivity. Furthermore, microRNAs such as miR-215 are also therapeutic targets. SUMMARY: These translational studies in osteosarcoma have identified new molecular targets for osteosarcoma. Copyright © Lippincott Williams & Wilkins.

Zhang Y.,Tianjin Medical University
Journal of Minimally Invasive Gynecology | Year: 2016

Study Objective: The study objective was to compare transvaginal intervention and laparoscopic repair for correcting the uterine defect in patients with previous cesarean scar defect (PCSD). Design: Retrospective study (Canadian Task Force classification). Setting: Previous studies have reported that transvaginal surgery and laparoscopic surgery are available treatment options for patients with PCSD. However, the two methods have not been compared before. Patients: A total of 124 patients with PCSD were included in the retrospective study between December 2010 and December 2014. Interventions: In the study, 65 patients received transvaginal repair, and 59 patients received laparoscopic repair. Measurements and main results: Operation time, blood loss, hospital stay length and hospitalization expense, clinical syndromes and healing of uterine defect 3 months postoperatively were compared between the two surgical approaches. Patients receiving transvaginal repair exhibited significantly shorter operation time and lower hospitalization expenses than the patients receiving laparoscopic repair. Follow-up data showed that prolonged menstrual bleeding syndrome was obviously improved in 89% of patients undergoing transvaginal intervention and 86% of patients undergoing laparoscopic repair. The uterine defect disappeared or was substantially reduced in 87% of patients undergoing transvaginal intervention and 86% of patients undergoing laparoscopic repair. The differences between the two surgical approaches were insignificant. Conclusion: Transvaginal repair is comparably effective to the laparoscopic repair and may be a more cost-effective and convenient surgical approach in the management of patients with PCSD. © 2016 AAGL.

Wang L.,Tianjin Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2013

To investigate the status of lymph node metastasis (LNM) and to discuss reasonable lymphadenectomy in early gastric cancer (EGC). Between January 1991 and December 2010, 242 EGC patients underwent surgery in the Tianjin Cancer Hospital. Their clinical characteristics, pathologic features, and lymph node metastasis were analyzed retrospectively. LNM was observed in 22 of 242 patients (9.1%), and 10 (5.5%) in 182 mucosal lesions and 12 (20.0%) in 60 submueosal lesions. There were 14 patients had LNM in the first tier alone, 4 patients had skipped metastasis, and 4 patients had LNM in the first, second, and third ties. The LNM was identified in 18 patients at the first tier with groups 7 and 3 being the most common (8 patients in each group), 7 patients at the second tier (4 patients in group 8a and 3 in group 9), and 2 patients at the third tier (one 16b, and one 4sa). Multivariable analysis showed that the depth of invasion (P=0.003, OR=4.386, 95%CI:1.656-11.617), and lymphatic vessel involvement(P=0.002, OR=13.621, 95%CI:2.711-68.447) were independent risk factors for LNM. LNM in EGC is mainly correlated with depth of invasion, and lymphatic vessel involvement. Precise evaluation of LNM pre- and intra-operatively is very important for the reasonable surgery.

Hu W.,Tianjin 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 evaluate the effectiveness of combined posterior decompression with laminoplasty and anterior decompression with fusion for the treatment of cervical spinal canal stenosis with reverse arch. Between May 2009 and February 2012, 13 cases of cervical spinal canal stenosis with reverse arch underwent posterior decompression with laminoplasty surgery in prone position and then anterior decompression with fusion surgery in supine position. There were 7 males and 6 females with an average age of 43.5 years (range, 38-62 years) and an average disease duration of 25 months (range, 18-60 months). All the patients had neck axial symptoms and spinal cord compressed symptoms, and lateral computer radiology (CR) of the neck showed reverse arch of cervical vertebrae. Segments of intervertebral disc protrusion included C3-6 in 4 cases, C4-7 in 4 cases, and C3-7 in 5 cases. After operation, anteroposterior and lateral CR was used to observe the cervical curvature change and fixation loosening, MRI to observe the change of the compression on spinal cord, visual analogue scale (VAS) score to evaluate the improvement of axial symptom, and Japanese Orthopaedic Association (JOA) score to assess the nerve function improvement. All incisions healed by first intention. All patients were followed up 9-32 months (mean, 15.4 months). Internal fixator had good position without loosening or breaking and the compression on spinal cord improved significantly after operation. All the patients obtained bony fusion at 6 months after operation. The axial symptoms and the nerve function at last follow-up were improved. VAS score at last follow-up (3.25 +/- 1.54) was significantly lower than that at preoperation (6.55 +/- 1.52) (P < 0.05); JOA score at last follow-up (10.45 +/- 4.23) was significantly higher than that at preoperation (7.05 +/- 1.32) (P < 0.05); and cervical curvature value at last follow-up [(6.53 + 3.12) mm] was significantly higher than that at preoperation [(3.22 +/- 5.15) mm] (P < 0.05). Combined posterior decompression with laminoplasty and anterior decompression with fusion for the treatment of cervical spinal canal stenosis with reverse arch is a safe and effective surgical method.

Zhang L.,Tianjin Medical University
Chinese Journal of Ophthalmology | Year: 2013

Objective: To investigate the expression of matrix metal proteinase (MMP)-2 and MMP-9 in adenoid cystic carcinoma of lacrimal gland as well as their relation with biological behaviour of adenoid cystic carcinoma. Methods: Experimental study. The research objects were 60 cases of adenoid cystic carcinoma of lacrimal gland which were collected from No. 2 Hospital of Tianjin Medical University from January 1991 to Jule 2011. There were 25 males and 35 females aged from 29 to 42 years. Based on histological revision, there were 36 cases of cribriform-tubular subtype and 24 cases of solid subtype. Forty-five cases were primary lesions and 15 cases were recurrent lesions. Ten samples of normal lacrimal gland around polymorphic adenoma were selected as the control group. The expression of CD105, MMP-2 and MMP-9 were evaluated by immunohistochemistry. The microvessel density (MVD) was defined by expression of CD105.One way ANOVA, χ2-test and spearman correlation test were used to analyzed the data. Results: The number of MVD[(17.71 ± 5.63)/100 folds field of vision] and the positive rates of MMP-2(45.0%, 27/60) and MMP-9 (55.0%, 33/60) in the samples of adenoid cystic carcinoma of lacrimal gland were higher than those in the normal lacrimal gland [the number of MVD was (0.70 ± 0.95)/100 folds field of vision, the expressions of MMP-2 and MMP-9 were negative] (t'= 2.039, P < 0.05; χ2=5.550, P < 0.05; χ2=8.315, P < 0.01), the solid subtypes had more MVD [(26.12 ± 5.32)/100 folds field of vision] and higher positive rates of MMP-2(62.5%, 15/24) and MMP-9(79.2%, 19/24) than the cribriform-tubular subtypes(t'= 2.060, P < 0.05; χ2 = 4.950, P < 0.05; χ2 = 9.439, P < 0.05); the recurrent lesions had more MVD and higher positive rate of MMP-2 and MMP-9 than the primary lesions (t' = 2.129, P < 0.05; χ2 = 9.899, P < 0.05; χ2 = 8.103, P < 0.05). The number of MVD in ACC of lacrimal gland patients was correlated with the positive rate of MMP-2 and MMP-9 respectively (rs=0.636, P < 0.05; rs=0.524, P < 0.05). Conclusions: The number of MVD and the expression of MMP-2 and MMP-9 are higher level in adenoid cystic carcinoma of lacrimal gland and are significantly correlated with pathological type and recurrence. Detecting the number of MVD and the expression of MMP-2 and MMP-9 may become biological indexes for malignancy, recurrence and metastasis of adenoid cystic carcinoma of lacrimal gland. Copyright © 2013 by the Chinese Medical Association.

Liu H.,Tianjin Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2013

To explore the prognostic factors and to compare chemotherapy alone versus surgical resection plus chemotherapy for early stage primary gastric diffuse large B-cell lymphomas (DLBCL). Clinical data of 75 patients who were diagnosed as primary gastric DLBCL between January 1993 and August 2008 in Cancer Institute and Hospital of Tianjin Medical University were reviewed retrospectively. Among these 75 patients, 20 patients received chemotherapy alone and 55 underwent surgical resection plus chemotherapy. Complete remission rates were 65.0% (13/20) and 83.6% (46/55), effective rates were 75.0% (15/20) and 92.7% (51/55), and 5-year survival rates were 86.9% and 78.7% respectively in chemotherapy alone group and resection plus chemotherapy group, while the differences were not statistically significant (all P>0.05). Multivariate Cox regression model showed that international prognosis index (IPI) was the only independent prognostic factor (P<0.05, HR=11.350, 95%CI:1.011-127.371). In early stage of DLBCL, IPI is the only independent prognostic factor. The clinical outcomes are comparable between chemotherapy alone and surgical resection plus chemotherapy.

Cao X.,Tianjin Medical University | Han Z.-B.,Peking Union Medical College | Zhao H.,Tianjin University of Commerce | Liu Q.,Peking Union Medical College
International Journal of Biochemistry and Cell Biology | Year: 2014

Alleviation of hyperglycemia in chemical-induced diabetic mice has been reported after bone marrow transplantation. Nevertheless, the underlying mechanism remains elusive. In the present study, we transplanted genetically labeled primary mouse mesenchymal stem cells into the pancreas of the streptozotocin-treated hyperglycemic isogeneic mice, resulting in a decrease in blood glucose due to a recovery in beta cell mass. Further analysis revealed that the increase in beta cell mass was predominantly attributable to beta cell replication. The grafted mesenchymal stem cells did not transdifferentiate into beta cells themselves but recruited and polarized macrophages in a Stromal cell-derived factor 1-dependent manner, which in turn promoted beta cell replication. Our finding thus suggests that transplantation of autogenic mesenchymal stem cells may increase functional beta cell mass by boosting beta cell replication in diabetes. © 2014 Elsevier Ltd.

Wang P.,Tianjin Medical University
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2013

To evaluate the cardioprotective effects of dexrazoxane (DEX) on breast cancer patients who received anthracycline-containing chemotherapy. A total of 122 breast cancer patients after operation were randomly divided into two groups: The experimental group of 61 cases treated with EPI plus DEX (DEX:EPI = 10:1) as adjuvant chemotherapy regimen, and the control group of 61 cases treated with EPI but without DEX. All patients received four cycles of adjuvant chemotherapy and their changes of specific cardiac functional status and hematology status before and after chemotherapy, as well as non-cardiac toxicity were observed and analyzed. Brain natriuretic peptide (BNP) before chemotherapy and after four cycles of chemotherapy in the control group was (106.78 ± 4.52)×10(-6) μg/ml and (187.19 ± 8.71)×10(-6) μg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (102.34 ± 8.76)×10(-6) μg/ml and (105.29 ± 7.21)×10(-6) μg/ml, respectively, without a significant difference (P > 0.05). Cardiac troponin T (cTnT) before chemotherapy and after four cycles of chemotherapy in the control group was (12.55 ± 2.73)×10(-3) μg/ml and ( 31.05 ± 7.10 )×10(-3) μg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (12.70 ± 2.15)×10(-3) μg/ml and (13.65 ± 7.82)×10(-3) μg/ml, respectively, without a significant difference (P > 0.05). The hart rate (HR) before chemotherapy and after four cycles of chemotherapy in the control group, was 75.32 ± 7.14 bpm and 89.60 ± 9.21 bpm, respectively, with a significant difference (P < 0.05). It in the experimental group was 78.60 ± 6.29 bpm and 83.10 ± 7.56 bpm, respectively, without a significant difference (P > 0.05). The left ventricular ejection fraction (LVEF) before chemotherapy and after four cycles of chemotherapy in the control group was (65.23 ± 7.82)% and (55.21 ± 7.23)%, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (64.12 ± 6.25)% and (59.6 ± 4.72)%, respectively, without a significant difference (P > 0.05). The absolute neutrophil count before chemotherapy and after four cycles of chemotherapy in the control group was (3.95 ± 1.36)×10(9)/L and (3.50 ± 1.52)×10(9)/L, respectively, without a significant difference (P > 0.05). It in the experimental group, was (4.96 ± 1.41)×10(9)/L and (3.10 ± 1.26)×10(9)/L, respectively, with a significant difference (P < 0.05). The incidence of grade I-IV bone marrow suppression in the experimental group was 21.3%, 16.4%, 24.6%, and 4.9%, respectively. It in the control group was 16.4%, 11.5%, 9.8%, and 5.5%, respectively, with a significant difference (P < 0.05). Cardiac toxicity after anthracycline treatment in breast cancer patients may be significantly reduced by DEX, without increase of non-cardiac and and non-hematologic toxicity. DEX combined with anthracycline increases the risk of bone marrow suppression, therefore, peripheral blood picture should be monitored or routine bone marrow support may be needed.

Zhang J.,Tianjin Medical University
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2011

This study was aimed to explore whether the perforin gene 1 (PRF1) mutation is the basis of genetic susceptibility to pathogenesis of acquired severe aplastic anemia (SAA). DNA exon2 and exon3 of PRF1 gene in peripheral blood mononuclear cells in 31 SAA patients and 15 normal controls were amplified by PCR; the sequencing was performed by using ABI pRISM 373OXL sequencer; the mutation loci were sought through checking sequences with GenBank-reported sequences; after the mutation sequences were found, those were cloned into M13 phage vector, then the corresponding sequences of gained 2 chromosomes were sequenced respectively to determine the distribution of different mutations on chromosomes. The results showed that (1) one homozygous mutation (822 C > T, synonymous mutation) and one heterozygous mutation (907 G > A, methionine 303 valine) were found in PRF1 coding region of 2 SAA patients. These mutations were not detected in normal controls. (2) 1 SNP (rs885822) in the coding region was detected in SAA patients and controls, and the heterozygosity rate between the 2 groups was different (p < 0.05). It is concluded that perforin gene mutation may be one risk factor in the aberrant proliferation and activation of cytotoxic T cells in pathogenesis of a part of patients with aplastic anemia.

Zhang D.,Peking Union Medical College | Zhang D.,Shantou University | Sun X.,Peking Union Medical College | Liu J.,Shantou University | And 4 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2015

Objective: Homocysteine can accelerate the senescence of endothelial progenitor cells or endothelial cells (ECs) via telomerase inactivation and length shortening. However, the underlying mechanism is unclear. Here, we investigated whether homocysteine promotes endothelial senescence by reducing the expression and activity of human telomerase reverse transcriptase (hTERT) by DNA methylation to reduce ECs telomerase activity.Approach and Results: When compared with primary human umbilical vein endothelial cells grown under standard conditions, ECs with chronic homocysteine treatment showed accelerated upregulation of p16, p21, and p53, markers of cellular senescence, during 6 to 10 passages. Interestingly, homocysteine-stimulated but not angiotensin II-stimulated ECs senescence could be reversed by hypermethylation induced by folic acid or s-adenosylmethionine supplementation. Meanwhile, homocysteine promoted the shortening of telomere length specifically related to restoration of hTERT transcriptional expression and CCCTC-binding factor binding sites with hTERT promoter hypomethylation, as detected by quantitative real-time polymerase chain reaction, Western blot, methylation-specific polymerase chain reaction, and bisulfite sequencing assay. Electrophoretic mobility shift assay and chromatin immunoprecipitation results showed that homocysteine-reduced telomere activity and homocysteine-induced EC senescence might contribute to hTERT promoter demethylation by increasing CCCTC-binding factor repression and interfering in the SP1 binding to the demethylated hTERT promoter, which might relate with reduced of DNA methyltransferase 1. Furthermore, the CCCTC-binding factor-dependent mechanism of homocysteine-reduced hTERT expression via DNA demethylation was confirmed in aortic endothelia of mice with hyperhomocysteine levels.Conclusions: CCCTC-binding factor and SP1 cross talk may contribute to homocysteine-reduced hTERT DNA methylation and expression in endothelial senescence. © 2014 American Heart Association, Inc.

Fu R.,Tianjin Medical University
Zhonghua yi xue za zhi | Year: 2010

To investigate the quantity and function of regulatory T cells in immune related pancytopenia (IRP) and explore the significance of Treg cells in the pathogenesis of IRP. Sixty-six IRP patients and 24 healthy donors were enrolled. The levels of IL-2 and TGF-β were detected by ELISA. The ratios of CD4(+)CD25(+)/CD4(+) and CD4(+)CD25(+)CD127(low)/CD4(+) in bone marrow were examined with flow cytometry. The expressions of Foxp3 and galectin-10 mRNA in BMMNC were measured by semi-quantitative RT-PCR. The levels of IL-2 and TGF-β in bone marrow of untreated or recovered IRP patients [(5.6 ± 1.7), (6.2 ± 2.5) μg/L, (1.8 ± 0.7), (1.9 ± 0.8) μg/L]were significantly lower than those of healthy controls [(7.9 ± 3.7), (2.5 ± 0.9) μg/L, all P < 0.05]. The ratio of CD4(+)CD25(+)/CD4(+) cells in bone marrow of untreated IRP patients (22.5% ± 9.5%) was significantly lower than that of recovered IRP patients or healthy controls (27.1% ± 7.1%, 30.6% ± 8.6%, both P < 0.05). The ratio of CD4(+)CD25(+)CD127(low)/CD4(+) cells in bone marrow of untreated IRP patients was significantly lower than that of recovered IRP patients or healthy controls (7.2% ± 2.7% vs 9.1% ± 4.7%, 10.4% ± 3.2%, both P < 0.05). The relative mRNA expressions of Foxp3 and galectin-10 were 0.34 ± 0.25, 0.69 ± 0.51, 0.82 ± 0.66 and 0.66 ± 0.11, 0.74 ± 0.11, 0.76 ± 0.09 in three groups respectively. The expressions of two factors in untreated IRP patients were significantly lower than those in recovered IRP patients or normal controls (all P < 0.05). The abnormalities in quantity and function of Treg cells in IRP patients might play an important role in the pathogenesis of IRP.

Liu D.,Tianjin Medical University
Journal of neurosurgery | Year: 2010

The goal of this study was to assess the long-term results of Gamma Knife surgery (GKS) in patients harboring an optic nerve sheath meningioma (ONSM). Thirty patients harboring an ONSM were treated with GKS between 1998 and 2003. Gamma Knife surgery was performed as the sole treatment option in 21 of these patients and resection had been performed previously in 9 patients. The mean volume of the tumor at the time of GKS was 3.6 cm(3) (range 1.4-9.7 cm(3)), and the mean prescription peripheral dose was 13.3 Gy (range 10-17 Gy). The mean number of isocenters used to treat these lesions was 8 (range 5-14 isocenters). At a median follow-up of 56 months, visual acuity improved in 11 patients, remained stable in 13 patients (including 4 patients who were completely blind before GKS), and deteriorated in 6 patients. Follow-up images were available in all patients and showed tumor regression in 20 patients and stable tumor in 8 patients. Persistent imaging evidence of progression was only present in 2 patients. With the exception of reversible conjunctival edema in 4 cases, no other serious acute side effect was observed. Gamma Knife surgery provides long-term tumor control for ONSM. The results of this study add substantial evidence that GKS may definitely become a standard treatment approach in selected cases of ONSM.

Li Y.,Nankai University | Yang X.,Tianjin Medical University | Xu C.,Nankai University | Zhang Y.,Nankai University | Zhang X.,Nankai University
International Journal of Colorectal Disease | Year: 2013

Objectives: The purpose of this study is to evaluate normal values and pressure morphology of three-dimensional high-resolution anorectal manometry (3D-HRM) in asymptomatic volunteers and to determine the relationship between objective measurable values, gender, and age. Patients and methods: Anorectal pressures and rectal sensation were evaluated in 110 asymptomatic volunteers (46 females and 64 males) ranging in age from 18 to 80 years (median age, 52 years) in left lateral position by three-dimensional high-resolution manometry. Results: Maximum squeeze pressure, residual anal pressure, and intrarectal pressure were significantly higher in males compared to females (p < 0.05 each). Duration of sustained squeeze was significantly lower in males compared to females (p < 0.05). Maximum resting pressure, mean resting pressure, and maximum squeeze pressure were inversely correlated (r = -0.310, p < 0.01, r = -0.276, p < 0.01, and r = -0.198, p < 0.05) with age. The value of rectoanal pressure differential was -13.1 ± 5.8 mmHg which was negative during defecation. Overall variation coefficient in anorectal pressures ranged between 0.21 and 0.34. Conclusion: This study establishes normal values for anorectal pressure by 3D-HRM in asymptomatic volunteers. There are significant gender differences concerning squeeze patterns. Increasing age is associated with lower maximum resting pressure, mean resting pressure, and maximum squeeze pressure. Normal characteristic pressure morphology of anorectum can be obtained at rest, during squeeze, and bear down as in defecation by 3D-HRM. © 2013 Springer-Verlag Berlin Heidelberg.

Ye H.,University of Wisconsin - Madison | Gemperline E.,University of Wisconsin - Madison | Venkateshwaran M.,University of Wisconsin - Madison | Chen R.,Tianjin Medical University | And 4 more authors.
Plant Journal | Year: 2013

Symbiotic associations between leguminous plants and nitrogen-fixing rhizobia culminate in the formation of specialized organs called root nodules, in which the rhizobia fix atmospheric nitrogen and transfer it to the plant. Efficient biological nitrogen fixation depends on metabolites produced by and exchanged between both partners. The Medicago truncatula-Sinorhizobium meliloti association is an excellent model for dissecting this nitrogen-fixing symbiosis because of the availability of genetic information for both symbiotic partners. Here, we employed a powerful imaging technique - matrix-assisted laser desorption/ionization (MALDI)/mass spectrometric imaging (MSI) - to study metabolite distribution in roots and root nodules of M. truncatula during nitrogen fixation. The combination of an efficient, novel MALDI matrix [1,8-bis(dimethyl-amino) naphthalene, DMAN] with a conventional matrix 2,5-dihydroxybenzoic acid (DHB) allowed detection of a large array of organic acids, amino acids, sugars, lipids, flavonoids and their conjugates with improved coverage. Ion density maps of representative metabolites are presented and correlated with the nitrogen fixation process. We demonstrate differences in metabolite distribution between roots and nodules, and also between fixing and non-fixing nodules produced by plant and bacterial mutants. Our study highlights the benefits of using MSI for detecting differences in metabolite distributions in plant biology. © 2013 The Authors.

Cai Y.,Tianjin Medical University
Journal of Medicine and Philosophy (United Kingdom) | Year: 2013

This article examines the impact of traditional Chinese culture on organ donation from the perspective of Confucianism, Buddhism, and Taoism. In each of these cultural systems, it appears that there are some particular sayings or remarks that are often taken in modern Chinese society to be contrary to organ donation, especially cadaveric organ donation. However, this article argues that the central concerns of Buddhism, Confucianism, and Taoism are "great love," "ren," and "dao," which can be reasonably interpreted to support organ donation. The author understands that each cultural system, in order to play its cultural function, must have its central concerns as well as relevant ritual practices (li) that incarnate its religious and ethical commitments. That is, each plays a general cultural role, which influences organ donation in particular not merely through abstract or general ethical principles and teachings, but through a combination of ethical teachings and the forming of particular ritual practices. This article contends that the primary reason Chinese individuals fail to donate sufficient cadaveric organs for transplantation is not because particular remarks or sayings from each of these systems appear to conflict with donation. Neither is it that the central concerns of these systems cannot support cadaveric donation. Rather, it is that modern Chinese individuals have failed to develop and secure relevant ritual practices that support the central concerns of organ transplantation. The article concludes that in order to promote more donations, there is a need to form relevant ritual practices supporting organ donation in conformity with the central concerns of these cultural systems. © The Author 2013.

Li Y.,Harbin Medical University | Xu J.,Harbin Medical University | Chen H.,Harbin Medical University | Bai J.,Harbin Medical University | And 7 more authors.
Nucleic Acids Research | Year: 2013

Glioma is the most common and fatal primary brain tumour with poor prognosis; however, the functional roles of miRNAs in glioma malignant progression are insufficiently understood. Here, we used an integrated approach to identify miRNA functional targets during glioma malignant progression by combining the paired expression profiles of miRNAs and mRNAs across 160 Chinese glioma patients, and further constructed the functional miRNA-mRNA regulatory network. As a result, most tumour-suppressive miRNAs in glioma progression were newly discovered, whose functions were widely involved in gliomagenesis. Moreover, three miRNA signatures, with different combinations of hub miRNAs (regulations≥30) were constructed, which could independently predict the survival of patients with all gliomas, high-grade glioma and glioblastoma. Our network-based method increased the ability to identify the prognostic biomarkers, when compared with the traditional method and random conditions. Hsa-miR-524-5p and hsa-miR-628-5p, shared by these three signatures, acted as protective factors and their expression decreased gradually during glioma progression. Functional analysis of these miRNA signatures highlighted their critical roles in cell cycle and cell proliferation in glioblastoma malignant progression, especially hsa-miR-524-5p and hsamiR-628-5p exhibited dominant regulatory activities. Therefore, network-based biomarkers are expected to be more effective and provide deep insights into the molecular mechanism of glioma malignant progression. © 2013 The Author(s).

To explore the effects of CD8(+)CXCR3(+)T cells on autoimmune hemolytic anemia (AIHA). Twenty-two AIHA patients, including 11 untreated and 11 recovered ones, and 23 normal controls were recruited from July 2010 to November 2010. The percentage of CD8(+)CXCR3(+)/CD8(+)T cells in peripheral blood and the expression of interleukin-10 (IL-10) in CD8(+)CXCR3(+)T cells were detected by flow cytometry. Their correlations with the count of CD3(+)CD4(+)cells and the percentage of CD5(+)CD19(+) in CD19(+) B cells were analyzed. The expression level of CXCR3 mRNA in PBMC was determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The percentage of CD8(+)CXCR3(+)/CD8(+) of untreated AIHA patients was (39.80 ± 19.96)%. And it was lower than that of recovered patients [(58.76 ± 14.22)%, P < 0.05] and normal controls [(59.66 ± 12.62)%, P < 0.01]. The percentage of IL-10(+) T cells in CD8(+)CXCR3(+)T cells of untreated patients was (22.98 ± 14.96)% and it was lower than that of normal controls [(38.15 ± 17.03)%, P < 0.05]. The expression level of CXCR3 mRNA for untreated AIHA patients was (0.51 ± 0.19) and it was lower than that of normal controls (1.67 ± 1.17, P < 0.01). The percentage of CD8(+)CXCR3(+)/CD8(+)T cells had a negative correlation with the count of CD3(+)CD4(+) cells and the percentage of CD5(+)CD19(+)/CD19(+) B cells (r = -0.571, -0.583, both P < 0.05). So did the percentage of IL-10(+) T cells in CD8(+)CXCR3(+)T cells (r = -0.524, -0.523, both P < 0.05). The decreased count of CD8(+)CXCR3(+)T cells and the lowered level of IL-10 may disturb the immune tolerance and lead to the occurrence of AIHA.

Cheng J.,Tianjin Medical University
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2012

To investigate the usefulness of (18)F-FDG PET/CT imaging in restaging, evaluating the treatment outcome, monitoring relapse and predicting prognosis of T-cell lymphoma. Retrospective analysis of PET/CT image results of thirty-four patients with T-cell lymphoma, and to evaluate its clinical significance in restaging, treatment efficiency, relapse monitor and prognosis prediction. Clinical restaging among the 20 stage I and II patients, 6 were ascended, 9 descended and 5 unchanged. Restaging among the other 14 stage III and IV patients, 3 were ascended, 4 descended and 7 unchanged. There were 12 patients in complete remission (CR), 11 in partial remission (PR), 2 in stable disease (SD) and 9 in progressive disease (PD) among all the 34 patients. There is obvious statistical difference of the standardized uptake value (SUV) between the efficacy group and the inefficacy group after treatment of 6 courses at least in 25 patients among all the 34 patients (P = 0.009). There is obvious statistical difference of the SUV value before and after treatment in 8 patients among all the 34 patients (P = 0.000). There is obvious statistical difference in the survival time between the efficacy group and the inefficacy group after treatment of 6 courses at least in 25 patients among all the 34 patients (P = 0.015). (18)F-FDG PET/CT imaging plays an very important role in guiding clinical restaging, evaluating the treatment outcome, monitoring relapse and predicting prognosis of T-cell lymphoma. It is helpful to establish personalized treatment planning.

Wang B.S.,Tianjin Medical University
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery | Year: 2012

To observe the effect of dexmedetomidine hydrochloride on stress responses during extubation in patients undergoing uvulopalatopharyngoplasty (UPPP). Eighty-six scheduled for UPPP under general anesthesia were randomly divided into dexmedetomidine group (group D, n = 50) and control group (group C, n = 36). All patients were transported into post anesthesia care unit (PACU) after surgery and maintained sedation and analgesia by infusing propofol and sufentanil. Patients in group D were administrated dexmedetomidine 0.5 μg/kg, group C were administrated equivalent volume of normal saline. Both groups were treated with mechanical ventilation 6 - 24 h before extubation. Recovery time, the dosage of sedative and analgesic drugs and side effects were recorded. There were no significant differences between two groups in recovery time (P > 0.05). The dosage of propofol and sufentanil in group D were respectively (785 ± 65) mg, (176 ± 10) μg, significantly less than that in group C (950 ± 101) mg, (209 ± 14) μg (P < 0.05). side effects in group D were significantly less than that in group C (P < 0.01). Dexmedetomidine hydrochloride could efficiently restrain the stress response around tracheal extubation, reduce postoperative complications in patients undergoing UPPP.

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

Magnolol is one of main active constituents from Magnolia officinalis, a widely used traditional Chinese medicine. Previous studies have proved its multiple pharmacological effects, such as anti-oxidation, anti-microbial and anti-tumor. In recent years, more and more studies have focused on magnolol both at home and abroad. This essay summarizes the advance in the latest studies on the pharmacological effects of magnolol, and briefs main problems in current studies and future development orientation.

Meng J.X.,Tianjin Medical University
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2012

Reactive oxygen species (ROS) is a kind of molecules derived by oxygen in the metabolic process of aerobic cells, which mainly includes superoxide, hydroxyl radicals, alkoxyl, hydrogen peroxide, hypochlorous acid, ozone, etc. They can destroy the structure and function of cells through the damage of biological macromolecules such as DNA, proteins and the lipid peroxidation. ROS also can regulate the proliferation, differentiation and apoptosis of cells through several signaling pathways and participate in fibrogenesis of many organs including hepatic and pulmonary fibrosis. Recent study shows that ROS might have an important effect on the forming of myelofibrosis. Consequently, ROS plays a significant role in the fibrogenesis of tissues and organs. In this review, the relevance between ROS and common tissues and organs fibrosis is summarized.

To assess the efficacy and safety of monoclonal antibody rituximab combined with cyclophosphamide (CTX) in the treatment of refractory and recurrent autoimmune hemolytic anemia. Seven cases with refractory and recurrent autoimmune hemolytic anemia (including 1 case of Evans syndrome) were recruited during January, 2007 to December, 2010. Treatment regimens were as follows: rituximab: 375 mg/m2, 1 time/week, 2-6 courses; CTX:1 g, 1/10 d, 2-7 courses; combined with intravenous immunoglobulin (IVIG) 5 g, 1 time/week, given 1 day after rituximab administration. The efficacy and safety of this regimen were assessed during follow-up. All the patients showed good responses (7/7). Six patients achieved complete remission (6/7) and one achieved partial remission (1/7). Average follow-up time for the patients was 27 months. All patients remained in remission during the 12-month follow-up visits. Two patients showed elevated indirect bilirubin and increased reticulocyte counts within 24 months. One patient achieved complete remission after additional rituximab therapy, and another patient remained partial remission after cyclosporine therapy. At the time of 36-month follow-up visit, the patient relapsed and was retreated with 3 courses of rituximab combined with CTX and eventually achieved partial remission. All patients tolerated the treatment well with few mild side effects. Rituximab combined with CTX is effective and relatively safe in patients with refractory and recurrent autoimmune hemolytic anemia. Additional treatment to relapse patients about 12 - 24 months after drug withdrawal continues to be effective.

Shi F.-D.,Tianjin Medical University | Shi F.-D.,Barrow Neurological Institute | Jia J.-P.,Capital Medical University
Neurology | Year: 2011

In the wake of dramatic economic success during the past 2 decades, the specialized field of neurology has undergone a significant transformation in China. With an increase in life expectancy, the problems of aging and cognition have grown. Lifestyle alterations have been associated with an epidemiologic transition both in the incidence and etiology of stroke. These changes, together with an array of social issues and institution of health care reform, are creating challenges for practicing neurologists throughout China. Notable problems include overcrowded, decrepit facilities, overloaded physician schedules, deteriorating physician-patient relationships, and an insufficient infrastructure to accommodate patients who need specialized neurologic care. Conversely, with the creation of large and sophisticated neurology centers in many cities across the country, tremendous opportunities exist. Developments in neurologic subspecialties enable delivery of high-quality care. Clinical and translational research based on large patient populations as well as highly sophisticated technologies are emerging in many neurologic centers and pharmaceutical companies. Child neurology and neurorehabilitation will be fast-developing subdisciplines. Given China's extensive population, the growth and progress of its neurology complex, and its ever-improving quality control, it is reasonable to anticipate that Chinese neurologists will contribute notably to unraveling the pathogenic factors causing neurologic diseases and to providing new therapeutic solutions. Copyright © 2011 by AAN Enterprises, Inc.

Wang Y.,Nankai University | Li S.J.,Nankai University | Pan J.,Nankai University | Che Y.,Nankai University | And 2 more authors.
Biochemical and Biophysical Research Communications | Year: 2011

The newly discovered human voltage-gated proton channel Hv1 is essential for proton transfer, which contains a voltage sensor domain (VSD) without a pore domain. We report here for the first time that Hv1 is specifically expressed in the highly metastatic human breast tumor tissues, but not in poorly metastatic breast cancer tissues, detected by immunohistochemistry. Meanwhile, real-time RT-PCR and immunocytochemistry showed that the expression levels of Hv1 have significant differences among breast cancer cell lines, MCF-7, MDA-MB-231, MDA-MB-468, MDA-MB-453, T-47D and SK-BR-3, in which Hv1 is expressed at a high level in highly metastatic human breast cancer cell line MDA-MB-231, but at a very low level in poorly metastatic human breast cancer cell line MCF-7. Inhibition of Hv1 expression in the highly metastatic MDA-MB-231 cells by small interfering RNA (siRNA) significantly decreases the invasion and migration of the cells. The intracellular pH of MDA-MB-231 cells down-regulated Hv1 expression by siRNA is obviously decreased compared with MDA-MB-231 with the scrambled siRNA. The expression of matrix metalloproteinase-2 and gelatinase activity in MDA-MB-231 cells suppressed Hv1 by siRNA were reduced. Our results strongly suggest that Hv1 regulates breast cancer intracellular pH and exacerbates the migratory ability of metastatic cells. © 2011 Elsevier Inc.

Nan Z.,Tianjin Medical University
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2013

This study was aimed to investigate the expression level and mechanism of microRNA-223 and LMO2 in acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) cells and the mechanism. MicroRNA-223 mimics was transfected to increase the expression of MicroRNA-223 in the lymphocytes sorted by ficoll separation from the bone marrow mononuclear cells (BMMNC) of ALL and CLL patients. MicroRNA-223 inhibitor was transfected to decrease the expression of the MicroRNA-223 in the lymphocytes of normal controls. Then the expression of the MicroRNA-223 and LMO2 in transfected lymphocytes before and after cultivating for 72 hours were detected by RT-PCR, the apoptosis and cell cycle of these cells were measured by flow cytometery. The results indicated that before the transfection, the expression of MicroRNA-223 in ALL and CLL cells was (433.11 ± 144.88), which was significantly lower than that in the normal lymphocyte (949.59 ± 267.39); the expression of LMO2 was (807.10 ± 238.41), which was significantly higher than that in the normal lymphocytes (455.32 ± 176.83) (P < 0.05); after the transfection, the expression of MicroRNA-223 was (571.86 ± 142.00) in ALL and CLL cells, which was significantly higher than that before transfection (P < 0.05), but the expression of LMO2 was significantly lower than that before transfection (651.97 ± 230.12) (P < 0.05); in the normal control the expression of MicroRNA-223 obviously decreased (646.32 ± 172.93) (P < 0.05), the expression of LMO2 was significantly increased (541.27 ± 158.86.2) (P < 0.05). After transfection, the cell cycle G1/G2 phase and apoptosis changed in ALL and CLL cells. Before transfection the cell ratio in cell cycle G1/G2 phase was (94.75 ± 3.15)%, the cell ratio in S phase was (5.14 ± 3.12)%; after transfection the cell ratio in cell cycle G1/G2 phase was (97.03 ± 2.08)% and obviously increased (P < 0.05), the cell ratio in S phase was (2.97 ± 2.08)% and significantly decreased (P < 0.05). Before transfection the apoptosis rate was (54.47 ± 8.72)%, and obviously was higher than that after transfection (60.48 ± 8.81)%. And in the normal control, the cell ratio in G1/G2 phase was significantly higher than that after transfection [(96.73 ± 2.26)%, (94.55 ± 2.77)%, P < 0.05)], and the cell ratio in S phase was significantly increased [(3.25 ± 2.26)%, (5.45 ± 2.77)% (P < 0.05)]. The apoptotic rate in the ALL and CLL patients was significantly higher than that after the transfection [(54.47 ± 8.72)% vs (60.48 ± 8.81)%, respectively (P < 0.05)]. The apoptotic rate in the normal control was significantly lower than that after the transfection [(59.02 ± 10.20)%, (51.96 ± 10.20)%, respectively (P < 0.05)]. It is concluded that the expression of MicroRNA-223 decreases, and the expression of LMO2 increases in lymphocytic leukemia cells which leads to the lymphocytes over-proliferation and abnormal apoptosis, thus may be one of pathogenesis in lymphocytic leukemia.

Ke B.,Tianjin Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2011

To investigate the risk factors for the prognosis in patients with node-negative gastric cancer. Clinicopathological characteristics of 138 patients with node-negative gastric carcinoma undergoing curative gastrectomy from January 2000 to December 2005 were retrospectively analyzed. The overall 5-year survival rate was 62.4%. The univariate analysis revealed that tumor size, tumor location, cell differentiation, invasive depth, operative type and Lauren histologic type had significant effects on the survival. The independent prognostic factors of these patients were tumor size, cell differentiation, and serosal involvement in multivariate analyses. For node-negative gastric cancer patients, tumor size, poor differentiation and serosal involvement are important markers to evaluate prognosis.

Hu J.L.,Tianjin Medical University
Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology | Year: 2011

To explore the relationship between myeloperoxidase (MPO) 129 A/G promoter polymorphisms and the severity of coronary artery disease (CAD). The study enrolled 267 patients who had been diagnosed as coronary artery diseases by coronary angiography. The serum MPO activity was detected by colorimetric method. PCR-RFLP method was used to decide the genotypes of the patients. The severity of CAD was evaluated by the numbers of stenotic coronary arteries and the Gensini scores respectively. The MPO 129 locus G and A alleles frequency were 0.893 and 0.107, respectively. No significant difference was observed in serum MPO activity between different genotypes (P > 0.05). The distribution of genotypes in different Gensini score groups had no significant difference (P > 0.05). The patients with GG genotypes were prone to develop mutivessel diseases. No significant correlation exists in MPO 129 locus polymorphism and serum MPO activity. The MPO 129 locus polymorphism isn't a reasonable predict factor of CAD severity.

Hao J.,Tianjin Medical University
OncoImmunology | Year: 2015

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal digestive tract malignancies. Hypoxia-inducible factor (HIF-1) is over-expressed in pancreatic cancer and associated with poor prognosis. During the past several years, we focused on identifying the function of HIF-1 and the antitumor effect of HIF-1 inhibitors on PDAC, especially in regards to immunogenic cell death. © 2015 Taylor & Francis Group, LLC.

Yang C.,Tianjin Medical University
International journal of surgical pathology | Year: 2012

St. Gallen 2005 expert consensus guideline modified its criteria for the risk category of breast cancer (BC) patients by integrating a combination of lymph nodes with metastasis (positive lymph nodes [PLNs]) and HER-2/neu status of tumor. Recently, some studies have shown that lymph node ratio (LNR), defined as the ratio of axillary lymph nodes with tumor metastasis to the total lymph nodes dissected, was a better independent prognostic indicator than PLN and should be considered as an alternative to the status of regional lymph nodes in the staging of breast cancer (pN). In the current study, the authors retrospectively reviewed 1095 primary BC patients with PLN and assessed the prognostic effect of LNR measured by relapse-free survival and overall survival to explore the feasibility of LNR and HER-2/neu status in stratifying the risk category of BC. Our results indicate that although by univariate analysis and when assessed as single covariate in multivariate analysis, both PLN and LNR were independent prognostic factors, PLN lost its significance when combined with LNR as covariates. A cutoff value of LNR = 0.30 was identified to show high accuracy in separating patients based on their survivals. The risk categories defined by LNR combined with HER-2/neu status were compatible to those defined by the PLN in combination with HER-2/neu status. LNR was a strong prognostic predictor of node-positive BC patients, superior to PLN. It should be considered as a new factor to couple with HER-2/neu status in defining risk category of BC patients.

Zhang B.-L.,Tianjin Medical University
Chinese Journal of Oncology | Year: 2012

Objective: We have identified a SNP within the seed-binding region for miR-502 in the 3′-UTR of the SET8 gene that codes for a methyltransferase for histone H4. SET8 methylates TP53 and thus regulates cell proliferation and genome stability. This study is to investigate the role for this SNP and its interaction with the TP53 codon 72 SNP in the age of onset of breast cancer. Methods: We conducted a case-only study of 1,110 breast cancer cases. PCR-RFLP was used for SNP genotyping. Ages of onset of breast cancer among different genotypes were analyzed using SAS software. Results: Our analysis revealed that the SET8 CC and TP53 GG genotypes were independently associated with earlier age of onset of breast cancer in an allele-dose dependent manner. Moreover, individuals with both SET8 CC and p53 GG genotypes developed cancer at age of 47.74 years, compared with 54.55 years for individuals with both SET8 TT and TP53 CC genotypes. Conclusions: miR-502-binding SNP in SET8 may modulate SET8 expression and contribute to early development of breast cancer either independently or together with the TP53 codon 72 SNP.

To explore the clinical value of combined detection of serum human epididymal secretory protein E4 (HE4) and CA(125) in the diagnosis of endometrial carcinoma. From Jan 2010 to Apr 2011, the serum specimens were collected from 124 cases of endometrial carcinoma, 97 cases of benign disease of uterus and 109 cases of healthy women. HE4 levels in the serum were detected by ELISA, and CA(125) levels in the serum were detected by the electro-chemiluminescent immunoassay. Those results were shown with median level. Accuracy of the diagnosis was evaluated by the area under the receiver operating characteristic curve (ROC-AUC). The median levels of HE4 and CA(125) were 78.09 pmol/L and 33.43 kU/L in serum of endometrial carcinoma group. The median levels of HE4 and CA(125) were 46.37 pmol/L and 18.26 kU/L in serum of benign disease of uterus group. The median levels of HE4 and CA(125) were 31.75 pmol/L and 12.64 kU/L in serum of healthy women group. The HE4 and CA(125) levels in serum of endometrial carcinoma group were significantly higher than those of benign disease of uterus group or healthy women group (all P < 0.05). Compared with that benign disease of uterus group, the ROC-AUC of HE4 and CA(125) in endometrial carcinoma group were 0.913 and 0.801, respectively. When the specificity was 95.0%, the sensitivities of HE4, CA(125), and combined detection of HE4 and CA(125) in endometrial carcinoma group were 41.1%, 22.6% and 46.0%, respectively. The positive rates of HE4 and CA(125) were 31% (27/86) and 12% (10/86) in stage I-II of endometrial carcinoma, while the positive rates were 63% (24/38) and 47% (18/38) in stage III-IV of endometrial carcinoma, in which there were significant difference between patients in stage III-IV and stage I-II (P < 0.01). The combined detection of serum HE4 and CA(125) is helpful to the diagnosis of endometrial carcinoma. The sensitivity, specificity and early diagnosis of HE4 are better than that of CA(125). The positive rates of HE4 and CA(125) in endometrial carcinoma are related to the clinical staging.

Ge Z.,Tianjin 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 explore the relative prognostic factors of Tile C pelvic injury after iliolumbar fixation. Between March 2007 and March 2010, 60 patients with Tile C pelvic injuries were surgically treated with iliolumbar fixation, including 39 males and 21 females with an average age of 37 years (range, 17-66 years). Of them, 27 cases were classified as Tile C1, 20 as Tile C2, and 13 as Tile C3. The preoperative injury severity score (ISS) was 12-66 (mean, 29.4). The time from injury to surgery was 2-25 days (mean, 8.1 days). Iliolumbar fixation was performed in all patients. Unconditional logistic analysis was used to analyze the relationship between the age, sex, body mass index (BMI), operation opportunity, the preoperative combined injury, classification of fracture, the postoperative complication, reduction outcome, sacral nerve injury, and the time of physical exercise and the prognosis. All 60 patients were followed up 12-56 months (mean, 27.3 months). Infection of incisions occurred in 12 cases and were cured after dressing change; healing of incision by first intention was obtained in the other patients. Delay sacral nerve injury was found in 15 patients, 6 patients underwent nerve decompression, and 9 underwent conservative treatment. Ten patients had nail protrusion of Schanz screws at the posterior superior illac spine, and 3 patients had pain, which was relieved after removal of the internal fixator. One patient had bone-grafting nonunion of sacroiliac joint, which was improved by pressured bone graft. Five patients had the beam breakage without significant effect. Six patients had deep vein thrombosis, among them 4 underwent filter and 2 underwent nonsurgical treatment. The healing time of fracture was 3-6 months (mean, 3.9 months). According to the Matta function score, the results were excellent in 31 cases, good in 24 cases, fair in 3 cases, and poor in 2 cases with an excellent and good rate of 91.7% at last follow-up. Majeed score was 58-100 (mean, 86), 28 were rated as excellent, 12 as good, 16 as fair, and 4 as poor with an excellent and good rate of 66.7%. The logistic analysis showed that the age, sex, BMI, and postoperative complications were not prognostic factors; early operation (within 10 days), early function exercises (within 7 days), the better reduction quality, and the less sacral nerve injury were in favor of prognosis; and the worse preoperative combined injury and pelvic injury were, the worse the prognosis was. Operation opportunity, the preoperative combined injury, reduction outcome, sacral nerve injury, and the time of physical exercise are all significantly prognostic factors of Tile C pelvic injuries.

Fang L.,Nanchang Hangkong University | Wang Y.,Tianjin Medical University | He X.,Nanchang Hangkong University
Optics Express | Year: 2013

The analysis of the change in residual wavefront aberrations after laser refractive surgery is important for the development of visual correction technology. Based on the ablation profile for wavefront-guided refractive surgery including optical zone and transition zone, the effect of pupil size on residual wavefront aberrations was studied. The research revealed that the optical zone to pupil ratio had a significant influence on the residual wavefront aberrations. The residual spherical aberration and coma were obviously larger than other individual Zernike higher-order terms when pupil diameter was larger than the optical zone size, and they increased rapidly as the pupil size increased. In addition, when the ablation zone diameter was kept constant, the residual higher-order aberrations increased rapidly as the blend coefficient increased for a 6mm or 7mm pupil. Furthermore, the residual higher-order aberrations with treatment decentration were distinctly larger than those without decentration. In the achievement of the best postoperative visual performance, the design of ablation profile played a crucial role in decrease of the residual wavefront aberrations after refractive surgery, especially optical zone size and the ablation pattern of transition zone. © 2013 Optical Society of America.

Chalyan D.A.,University of California at Irvine | Chalyan D.A.,University of Iowa | Zhang Z.,University of California at Irvine | Zhang Z.,Tianjin Medical University | And 2 more authors.
Circulation: Cardiovascular Interventions | Year: 2014

Background-Diastolic fractional flow reserve (dFFR) has been shown to be highly sensitive for detection of inducible myocardial ischemia. However, its reliance on measurement of left-ventricular pressure for zero-flow pressure correction, as well as manual extraction of the diastolic interval, has been its major limitation. Given previous reports of minimal zero-flow pressure at end-diastole, we compared instantaneous ECG-gated end-diastolic FFR with conventional fullcardiac cycle FFR and other diastolic indices in the porcine model. Methods and Results-Measurements of FFR in the left anterior descending and left circumflex arteries were performed in an open-chest swine model with an external occluder device on the coronary artery used to produce varying degrees of epicardial stenosis. An ultrasound flow-probe that was placed proximal to the occluder measured absolute blood flow in ml/min, and it was used as a gold standard for FFR measurement. A total of 17 measurements at maximal hyperemia were acquired in 5 animals. Correlation coefficient between conventional mean hyperemic FFR with pressure-wire and directly measured FFR with flow-probe was 0.876 (standard error estimate=0.069; P<0.0001). The hyperemic enddiastolic FFR with pressure-wire correlated better with FFR measured directly with flow-probe (r=0.941, standard error estimate=0.050; P<0.0001). Conclusions-Instantaneous hyperemic ECG-gated FFR acquired at end-diastole, as compared with conventional full-cardiac cycle FFR, has an improved correlation with FFR measured directly with ultrasound flow-probe. © 2014 American Heart Association, Inc.

Wang N.,Capital Medical University | Li H.,Beijing University of Technology | Lu W.,Tianjin Medical University | Li J.,Capital Medical University | And 3 more authors.
Biomaterials | Year: 2011

Titanium dioxide (TiO2) nanotubes can accelerate the adhesion and differentiation of osteoblasts, yet little is known how this nano-modified implant surface affects osseointegration at molecular level in vivo. The aim of this study was to investigate the effects of TiO2 nanotubes with different diameters (30nm, 70nm and 100nm) on biological attachment mechanism of implants to bone in vivo by studying the gene expression and bone formation around the implants. The histological features and fluorochrome labeling changes of bone around implants on the non-decalcified sections (at 3, 5 and 8 weeks after implantation) were investigated by using traditional light- and fluorescent microscopy, and the gene expression of alkaline phosphatase (ALP), osterix (Osx), collagen-I (Col-I) and tartrate-resistant acid phosphatase (TRAP) was examined by using real-time PCR at 1, 2, 3, 4 and 5 weeks after implantation. Comparing with machined titanium implants, a significant increase in bone-implant contact (BIC) and gene expression levels was found in the bone attached to implants with TiO2 nanotubes, especially with 70nm diameter nanotubes. At the same time, the sequential fluorescent labeling images illustrated dynamic bone deposition. In conclusion, TiO2 nanotubes can modulate bone formation events at the bone-implant interface as to reach favorable molecular response and osseointegration; in addition, the diameters of nanotubes can be precisely controlled in order to obtain better bone formation. © 2011 Elsevier Ltd.

Gao J.,Tianjin Medical University
Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas / Sociedade Brasileira de Biofísica ... [et al.] | Year: 2013

The multidrug resistance 1 gene (MDR1) is an important candidate gene for influencing susceptibility to hepatocellular carcinoma (HCC). The objective of the present study was to evaluate the association of MDR1 polymorphisms with the risk of HCC in the Chinese Han population. A total of 353 HCC patients and 335 healthy subjects were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), created restriction site-PCR (CRS-PCR) and DNA sequencing methods were used to identify MDR1 gene polymorphisms. Two allelic variants (c.335T>C and c.3073A>C) were detected. The CC genotype of the c.335T>C polymorphism was associated with an increased risk of developing HCC compared to the TT genotype (OR = 2.161, 95%CI = 1.350-3.459, χ2 = 10.55, P = 0.0011). The risk of HCC was significantly higher for the CC genotype in the c.3073A>C polymorphism compared to the AA genotype in the studied populations (CC vs AA: OR = 2.575, 95%CI = 1.646-4.028, χ2 = 17.64, P < 0.0001). The C allele of the c.335T>C and c.3073A>C variants may contribute to the risk of HCC (C vs T of c.335T>C: OR = 1.512, 95%CI = 1.208-1.893, χ2 = 13.07, P = 0.0003, and C vs A of c.3073A>C: OR = 1.646, 95%CI = 1.322-2.049, χ2 = 20.03, P < 0.0001). The c.335T>C and c.3073A>C polymorphisms of the MDR1 gene were associated with the risk of occurrence of HCC in the Chinese Han population. Further investigations are needed to confirm these results in larger different populations.

Yang J.,Tianjin Medical University
Chinese journal of cancer | Year: 2012

To investigate the clinical characteristics of chondroblastoma with an emphasis on lesions located in the long bone diaphysis, we reviewed the clinical data of 7 patients with histologically proven chondroblastoma treated in Tianjin Medical University Cancer Hospital and Fudan University Cancer Hospital between January 1995 and May 2009. There were two rare cases of chondroblastoma in the long bone diaphysis. One patient with a lesion in the tibial diaphysis underwent intralesional curettage and bone grafting, and the postoperative bone function was measured as excellent according to the Enneking scoring system. The patient was still alive upon follow-up at 60 months. The other patient with a lesion in the humeral diaphysis underwent resection, and the postoperative bone function was excellent at 48 months, at which there was no evidence of recurrence or metastasis. Thus, except for the distinctive site of the long bone diaphysis, which made diagnosis difficult, the patients' ages, symptoms, X-ray and CT images, treatment, and prognosis were in accordance with typical lesions in the epiphysis and metaphysis. The diagnosis of chondroblastoma in the long bone diaphysis significantly depends on histopathologic characteristics.

Wang C.L.,Tianjin Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2011

To study the prognosis and prognostic factors of non-small-cell lung carcinoma (NSCLC) according the new TNM stage system. Clinic data of 1638 inpatient cases admitted from January 2001 to January 2005 were retrospectively reviewed. There were 1083 male and 555 female patients in the study and the average age was 59.5 years. All the patients received surgical procedures. The overall 1, 3, 5-year survival rate was 80.0%, 52.3%, 39.0%. The main prognostic factors were bronchial stump, operation type, T stage, N stage, the number of lymph nodes (LNs) in lymph nodes dissection (1 - 10, 11 - 20, and > 20), overall N stations (< 4 and ≥ 4) and postoperative radiotherapy (all P < 0.05). Cox regression suggested that T stage (P = 0.000), N stage (P = 0.000), operation type (P = 0.001) and LNs (P = 0.013) were independent factors affecting the prognosis. The overall survival rate of NSCLC is poor. T stage, N stage, operation type and LNs are independent factors affecting the prognosis.

Tan T.,Tianjin Medical University
Sheng li xue bao : [Acta physiologica Sinica] | Year: 2011

Synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), is widely considered as one of the major mechanisms underlying learning and memory. This study explored hippocampal synaptic plasticity and spatial memory formation of an Alzheimer's disease (AD) rat model established by intrahippocampal injection of oligomeric Aβ(1-42). Twenty four Sprague-Dawley rats at 2.5 months of age were randomly divided into AD and control groups, and were bilaterally injected with 5 μg oligomeric Aβ(1-42) or normal saline into dentate gyrus (DG) of hippocampus. Morris water maze test was used to observe the capability of learning and memory of two groups, 30 d after injection. To investigate the variations of paired-pulse facilitation (PPF) and range of synaptic plasticity, field potentials were recorded in the DG of the dorsal hippocampus by stimulating the perforant path (PP). The results showed that oligomeric Aβ(1-42) obviously impaired spatial memory formation in rats (P < 0.05). Furthermore, oligomeric Aβ(1-42) reduced the PPF ratio (P < 0.05) and hippocampal LTP formation (P < 0.05), while facilitated the hippocampal LTD formation (P < 0.05). These data suggest that chronic Aβ aggregation impairs synaptic plasticity of hippocampal PP-DG pathway, which may be involved in the spatial memory deficit in AD rats.

Niu Y.,University of Rochester | Niu Y.,Tianjin Medical University | Chang T.-M.,University of Rochester | Yeh S.,University of Rochester | And 4 more authors.
Oncogene | Year: 2010

Prostate cancer is one of the major causes of cancer-related death in the western world. Androgen-deprivation therapy (ADT) for the suppression of androgens binding to the androgen receptor (AR) has been the norm of prostate cancer treatment. Despite early success to suppress prostate tumor growth, ADT eventually fails leading to recurrent tumor growth in a hormone-refractory manner, even though AR remains to function in hormone-refractory prostate cancer. Interestingly, some prostate cancer survivors who received androgen replacement therapy had improved quality of life without adverse effect on their cancer progression. These contrasting clinical data suggest that differential androgen/AR signals in individual cells of prostate tumors can exist in the same or different patients, and may be used to explain why ADT of prostate cancer fails. Such a hypothesis is supported by the results obtained from transgenic mice with selective knockout of AR in prostatic stromal vs epithelial cells and orthotopic transplants of various human prostate cancer cell lines with AR over-expression or knockout. These studies concluded that AR functions as a stimulator for prostate cancer proliferation and metastasis in stromal cells, as a survival factor of prostatic cancer epithelial luminal cells, and as a suppressor for prostate cancer basal intermediate cell growth and metastasis. These dual yet opposite functions of the stromal and epithelial AR may challenge the current ADT to battle prostate cancer and should be taken into consideration when developing new AR-targeting therapies in selective prostate cancer cells. © 2010 Macmillan Publishers Limited All rights reserved.

Lu H.Y.,Tianjin Medical University
Zhonghua yi xue za zhi | Year: 2010

OBJECTIVE: To investigate the clinical features and specific characteristics of magnetic resonance image (MRI) in preeclampsia-eclampsia patients with reversible posterior leukoencephalopathy syndrome (RPLS). METHODS: The investigators analyzed the combined clinical, laboratory and neuroradiographic features of 20 preeclampsia-eclampsia patients with RPLS and 15 preeclampsia-eclampsia controls with normal MRI findings. RESULTS: Patients with RPLS had more tendency to have headache, seizure, visual disturbance, confusion and altered mental status than controls. Neuroimaging showed diffuse edema predominantly in posterior cerebral white matter bilaterally. Clinical features and neuroradiological alterations disappeared after appropriate treatments were started. Twenty RPLS patients had a significantly higher level of uric acid (442 +/- 77 mmol/L) than those without RPLS (350 +/- 88 mmol/L) (P < 0.05). However no difference was observed for other indices. CONCLUSION: Preeclampsia-eclampsia patients with RPLS have typical clinical and imaging findings, and the syndrome is reversible with appropriate treatment. Perhaps endothelial damage is related to the pathogenesis of RPLS. Monitoring the level of uric acid in patients with preeclampsia-eclampsia is of vital significance to discover RPLS in an early stage.

Sun Z.-F.,Tianjin Medical University
Chinese Journal of Oncology | Year: 2012

Objective: To study the expression of Notch1, MMP-2 and MMP-9 in glioma patients and their relationship with progression and prognosis of gliomas. Methods: Sixty-four cases of glioma were included in this study. There were four cases of grade 1 tumor, twenty-five cases of grade 2, nine cases of grade 3, and twenty-six cases of grade 4. Immunohistochemistry (SP staining method) was used to detect the expression of Notch1, MMP-2 and MMP-9 in glioma tissues and adjacent non-tumor tissues, and the patients were followed up. Results: Notch1, MMP-2 and MMP-9 were detected in glioma tissues but not in adjacent non-tumor tissues. The expression of Notch1 was increased with the pathological grade of the gliomas (r = 0.262, P < 0.05). The survival time of patients with strong expression of Notch1 was 31.0 months, significantly shorter than that of patients with non-strong positive (negative, weak and moderately) Notch1 expression (53.0 months, P < 0.05). Significant difference in survival time was observed between patients with negative and positive expression of MMP-9 (P < 0.05). Conclusions: Notch1, MMP-2 and MMP-9 are closely correlated with the progression and prognosis of malignant gliomas. Notch1 may participate in the expression regulation of MMP-2 and MMP-9. Compared with MMP-2, MMP-9 may play a more important role in determining the prognosis of malignant glioma. Notch1 and MMP-9 may become new biological markers for prognosis of patients with malignant glioma.

Li Y.,Tianjin Medical University
Chinese Critical Care Medicine | Year: 2014

Objective: To inevestigate the role of Nrf2 on hydrogen treatment for intestinal injury caused by severe sepsis. Methods: 152 male ICR mice were randomly divided into four groups: sham operation group, hydrogen control group, sepsis group, and hydrogen treatment group, each n=38. Sepsis model was reproduced by cecal ligation and puncture (CLP). The mice in sham operation group and hydrogen control group did not receive CLP, and the operative procedure was the same as follows. The mice in hydrogen control group and hydrogen treatment group received 1-hour inhalation of 2% hydrogen 1 hour and 6 hours after sham operation or CLP. Twenty animals in each group were selected and observed for 7-day survival rate. Eighteen animals in each group were selected and sacrificed at 6, 12 and 24 hours after CLP. The intestinal tissues were obtained to determine the expression of Nrf2 and high mobility group B1 (HMGB1) protein by Western Blot, and the expression of Nrf2 mRNA by reverse transcription-polymerase chain reaction (RT-PCR). The middle portion of jejunum was obtained to evaluate the degree of septic injury by light microscope after hematoxylin and eosin (HE) staining. Results: There was no statistical significance in variables between sham operation group and hydrogen control group. Compared with sham operation group, the 7-day survival rate was significantly decreased in sepsis group (0 vs. 100%, P<0.05); compared with sepsis group, the 7-day survival rate was significantly increased in hydrogen treatment group (55% vs. 0, P<0.05). Compared with sham operation group, the expression of Nrf2 protein (gray value) and Nrf2 mRNA were up-regulated in sepsis group at 6, 12 and 24 hours after CLP (Nrf2 protein 6 hours: 1.973 ± 0.350 vs. 1.000 ± 0.000, t=4.411, P=0.002; 12 hours: 2.367 ± 0.186 vs. 1.000 ± 0.000, t=10.210, P=0.000; 24 hours: 2.517 ± 0.280 vs. 1.000 ± 0.000, t=9.521, P=0.000; Nrf2 mRNA 6 hours: 1.606 ± 0.271 vs. 1.000 ± 0.000, t=3.631, P=0.002; 12 hours: 1.692 ± 0.399 vs. 1.000 ± 0.000, t=3.233, P=0.005; 24 hours: 1.784 ± 0.341 vs. 1.000 ± 0.000, t=3.894, P=0.001), and it was also the expression of HMGB1 (gray value) at 24 hours after CLP operation (1.507 ± 0.220 vs. 1.000 ± 0.000, t=3.948, P=0.004). Compared with sepsis group, the expression of Nrf2 protein and Nrf2 mRNA in intestines were up-regulated at 6, 12 and 24 hours after CLP in hydrogen treatment group (Nrf2 protein 6 hours: 2.583 ± 0.395 vs. 1.973 ±0.350, t=2.165, P= 0.024; 12 hours: 2.725 ± 0.235 vs. 2.367 ±0.186, t=2.674, P=0.028; 24 hours: 2.930 ± 0.212 vs. 2.517 ± 0.280, t=2.595, P=0.032; Nrf2 mRNA 6 hours: 2.008 ± 0.400 vs. 1.606 ± 0.271, t=2.405, P=0.029; 12 hours: 2.188 ± 0.475 vs. 1.692 ± 0.399, t=2.317, P=0.034; 24 hours: 2.333 ± 0.406 vs. 1.784 ± 0.341, t=2.728, P=0.015). Compared with sepsis group, the expression of HMGB1 was down-regulated significantly at 24 hours after CLP in hydrogen treatment group (1.147 ± 0.152 vs. 1.507 ± 0.220, t=2.805, P=0.023). HE staining showed that there was significantly aggravated intestinal pathological injury in the mice of sepsis group; compared with sepsis group, the pathology was significantly less marked in hydrogen treatment group. Conclusion: Through activation of Nrf2-antioxidant response element (ARE) pathway, hydrogen may increase the level of Nrf2, which is a kind of protective protein, in the intestine of mice, thus decreases the level of late pro-inflammatory factor, HMGB1, and it may protect the intestinal tissues in septic mice and increase the survival rate significantly.

Wang X.,Shandong University | Cao X.,Tianjin Medical University
Tumor Biology | Year: 2014

The molecular mechanism underlying metastasis of pediatric multiple myeloma (MM) remains elusive. Here, we showed that the levels of MMP13 are significantly higher in MM from young patients than those from adult patients. Moreover, a strong correlation of the MMP13 and phosphorylated fibroblast growth factor receptor 4 (FGFR4) levels was detected in MM from young patients. To prove a causal link between activation of fibroblast growth factor receptors (FGFR) signaling pathway and MMP13 expression, we used a human MM line, RPMI-8226 (8226), to study the underlying molecular basis. We found that FGF1-induced FGFR4 phosphorylation in 8,226 cells resulted in significant activation of MMP13, and consequently, an increase in cancer invasiveness. FGFR4 inhibition in 8,226 cells abolished FGF1-stimulated MMP13 expression, suggesting that activation of FGFR signaling pathway in MM may promote cancer metastasis by inducing MMP13 expression. To define the signaling cascades downstream of FGFR4 activation for MMP13 activation, we applied specific inhibitors for PI3K, Jun N-terminal kinase (JNK), and ERK/MAPK, respectively, to the FGF1-stimulated 8,226 cells. We found that only inhibition of ERK1/2 significantly decreased the activation of MMP13 in response to FGF stimulation, suggesting that activation of FGFR signaling may activate ERK/MAPK, rather than JNK or PI3K pathway to activate MMP13 expression in 8,226 cells. Our study thus highlights FGFR4 signaling pathway and MMP13 as novel therapeutic targets for MM. © 2014, International Society of Oncology and BioMarkers (ISOBM).

Zhao E.,Nankai University | Liang Y.,Nankai University | Fan H.,Tianjin Medical University
Optics Communications | Year: 2013

Based on the continuity of adjacent slices in a medical image sequence, a slice-based 3-D segmentation framework is constructed to extract the intact kidney by processing all slices automatically in the whole sequence. The framework includes four sections: initial segmentation, selection of the most reliable initial segmentation, location and modification of leakage. The crucial section of the proposed framework is selecting the most reliable initial segmentation image, which will be regarded as the reference image to evaluate the continuity of the following slice. Leakage location is carried out based on the contextual features, and the local iterative thresholding (LIT) is used to modify the leakage. As test examples of the framework, abdominal computed tomography (CT) images in enhanced phases are processed to segment kidney automatically. The total of 392 CT images in 7 sequences from 3 patients are selected as training images to determine the parameters in the database, and other 898 CT images in 21 sequences from 7 patients are used as test images to evaluate the effectiveness of the method. An average of three dimensional Dice similarity coefficient (3-D DSC) of 94.7% and average symmetric surface distance (ASSD) of 0.91 mm are obtained, which indicate that the intact kidney can be perfectly extracted with hardly any leakage automatically. © 2012 Elsevier B.V. All rights reserved.

Li W.-Q.,Harvard University | Li W.-Q.,University of Rhode Island | Qureshi A.A.,Harvard University | Qureshi A.A.,University of Rhode Island | And 5 more authors.
JAMA Internal Medicine | Year: 2014

IMPORTANCE The RAS/RAF/mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK) kinase/ERK cascade plays a crucial role in melanoma cell proliferation and survival. Sildenafil citrate (Viagra) is a phosphodiesterase (PDE) 5A inhibitor commonly used for erectile dysfunction. Recent studies have shown that BRAF activation down-regulates PDE5A levels, and low PDE5A expression by BRAF activation or sildenafil use increases the invasiveness of melanoma cells, which raises the possible adverse effect of sildenafil use on melanoma risk. OBJECTIVE To evaluate the association between sildenafil use and risk of incident melanoma among men in the United States. DESIGN, SETTING, AND PARTICIPANTS Our study is a prospective cohort study. In 2000, participants in the Health Professionals' Follow-up Study were questioned regarding sildenafil use for erectile dysfunction. Participants who reported cancers at baseline were excluded. A total of 25 848 men remained in the analysis. MAIN OUTCOMES AND MEASURES The incidence of skin cancers, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC), was obtained in the self-reported questionnaires biennially. The diagnosis of melanoma and SCC was pathologically confirmed. RESULTS We identified 142 melanoma, 580 SCC, and 3030 BCC cases during follow-up (2000-2010). Recent sildenafil use at baseline was significantly associated with an increased risk of subsequent melanoma with a multivariate-adjusted hazard ratio (HR) of 1.84 (95%CI, 1.04-3.22). In contrast, we did not observe an increase in risk of SCC (HR, 0.84; 95%CI, 0.59-1.20) or BCC (1.08; 0.93-1.25) associated with sildenafil use. Moreover, erectile function itself was not associated with an altered risk of melanoma. Ever use of sildenafil was also associated with a higher risk of melanoma (HR, 1.92; 95%CI, 1.14-3.22). A secondary analysis excluding those reporting major chronic diseases at baseline did not appreciably change the findings; the HR of melanoma was 2.24 (95%CI, 1.05-4.78) for sildenafil use at baseline and 2.77 (1.32-5.85) for ever use. CONCLUSIONS AND RELEVANCE Sildenafil use may be associated with an increased risk of developing melanoma. Although this study is insufficient to alter clinical recommendations, we support a need for continued investigation of this association. Copyright 2014 American Medical Association. All rights reserved.

Zhang X.-H.,Tianjin Medical University
Medical Hypotheses | Year: 2013

Metastasis is so complicated and well organized that there should be a good reason for it to happen. Here a hypothesis is proposed that metastasis of cancer cells is an abnormal form of migration of native stem/progenitor cells since cancer cells derive from stem/progenitor cells and may inherit stemness, including migration ability. This is an intrinsic potential and external cause mode. During metastasis, cancer cells are involved in the stem/progenitor cell recruitment to meet the need of organism for homeostasis, regeneration and repair, mediated by external signals and using inherent mechanisms but leading to catastrophic results. The " seed and soil" hypothesis can be redefined as that the " soil" is formed under certain circumstances and the " seed" is attracted to its particular " soil" Cancer cells in the microenviroment mimicking stem cell niche may have superiority in reactivity to metastatic signals. And very few of migrating cancer cells can form metastases. The conditions suitable for metastasis formation are still waiting to be revealed. The hypothesis tries to explain why cancer cells metastasize. It is hoped that the examination of this hypothesis may lead us to the real answer. © 2013 Elsevier Ltd.

Ba Y.,Tianjin Medical University
Chinese Journal of Clinical Oncology | Year: 2013

Multidisplinary treatment is the mordent means of local-regional gastric cancer therapy, and individualized treatment decisions are dependent on the patient's characteristics. Stage II patients previously treated with standard D2 resection should receive oral administration of S-1 or combination chemotherapy of XELOX. However, patients at stage IIIb or at a more advanced stage should receive combination treatment as priority. Concurrent radiochemotherapy was recommended to treat patients that had been operated by D0 or D1 resection. Perioperative chemotherapy is more reasonable than pure neoadjuvant chemotherapy. No evidence has verified that perioperative or neoadjuvant chemotherapy leads to better survival compared with postoperative adjuvant chemotherapy. The value of chemotherapy before operation is rest with the effect of downstaging and conversion of the unresectable tumor to a resectable one. Concurrent radiochemotherapy prior to an operation needs further investigation to affirm its high efficacy of downstaging and conversion.

Chen P.,Tianjin Medical University | Li L.,CAS Institute of Physics
Chinese Journal of Clinical Oncology | Year: 2013

Lung cancer is the most common cancer worldwide, accounting for approximately 18% of all cancer-related deaths. Circulating tumor cells (CTCs) have the capacity to spread into the blood stream. This capacity of CTCs is one of the most critical factors for unfavorable clinical outcome of patients with NSCLC. Detection of CTCs using a simple blood test may assist in early detection of lung cancer. Researchers have attempted to isolate CTCs from peripheral blood using various techniques. Although reports on CTC detection are abundant, methodological aspects concerning sensitivity, specificity, and reproducibility have prevented a clear appraisal of the clinical impact. This paper gives a brief description of each CTC detection method.

Yang R.,Tianjin Medical University | Yeh A.,Wang Vision Cataract and Center | George M.R.,Tylock Eye Care and Laser Center | Rahman M.,University of Tennessee at Knoxville | And 2 more authors.
Journal of Cataract and Refractive Surgery | Year: 2013

Purpose: To compare the accuracy of intraocular lens (IOL) power calculation methods for post-myopic excimer laser surgery patients without previous refractive surgery data using the Holladay IOL Consultant Program and the American Society of Cataract and Refractive Surgery (ASCRS) IOL Power Calculator. Setting: Wang Vision Cataract and LASIK Center, Nashville, Tennessee, USA. Design: Case series. Methods: Eight methods were used to calculate IOL power: Holladay 2 partial coherence interferometry (PCI)-K, Holladay 2 FlatK, Wang-Koch-Maloney, Shammas No-History, Haigis-L, ASCRS-Average, ASCRS-Min, and ASCRS-Max. The optimum IOL power corresponding to the target refraction was back-calculated using the stable post-cataract surgery refraction and implanted IOL power. Using the optimum IOL power, the predicted IOL power error and the resultant refractive error with each method were calculated and compared. Results: The Holladay 2 FlatK method was most accurate for IOL power calculation, followed by the Holladay 2 PCI-K, ASCRS-Min, Wang-Koch-Maloney, ASCRS-Average, Shammas No-History, Haigis-L, and ASCRS-Max. Statistically significant differences were observed between Holladay 2 FlatK and Holladay 2 PCI-K (P<.05), Wang-Koch-Maloney and ASCRS-Average (P<.05), and Haigis-L and ASCRS-Max (P<.01). No statistically significant differences were observed between the Holladay 2 PCI-K, ASCRS-Min, and Wang-Koch-Maloney or between the ASCRS-Average, Shammas No-History, and Haigis-L (both P>.05). Conclusions: The Holladay 2 FlatK method provided the most accurate IOL power in eyes without previous myopic laser surgery data. If the Holladay IOL Consultant Program is unavailable, the ASCRS methods can be used; the ASCRS-Min represents the most accurate method. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. © 2013 ASCRS and ESCRS Published by Elsevier Inc.

Chen C.G.,Tianjin Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2013

To explore the level of serum high-mobility group box 1 (HMGB1) in patients with esophageal squamous cell carcinoma (ESCC) and the feasibility of HMGB1 as a tumor marker. Serum HMGB1, carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen (Cyfra21-1) and squamous cell carcinoma antigen (SCC) were measured by enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence immunoassay (ECLIA) and microparticle enzyme immunoassay (MEIA) respectively in 78 patients with ESCC preoperatively as well as a month after esophagectomy. At the same time, serum HMGB1, CEA, Cyfra21-1 and SCC of 60 healthy adult volunteers were detected with the same method. The unilateral P95 value of serum HMGB1 (>96 μg/L) was defined as positive. According to the Roche kit diagnostic criteria, CEA>5.0 μg/L, Cyfra21-1>3.3 μg/L and SCC>1.5 μg/L were defined as positive. The preoperative positive ratio of serum HMGB1 in 78 patients with ESCC was 84.6%, and the level of serum HMGB1 was associated with the tumor size, infiltration depth, lymph node metastasis and tumor stage (P<0.01 or P<0.05). One month after esophagectomy, the level of serum HMGB1 in ESCC declined significantly compared with the preoperative level (P<0.01), and the level of serum HMGB1 in T4, N1, stage III was higher compared to corresponding T, N and tumor stage (P<0.01 or P<0.05). The positive ratio of CEA, Cyfra21-1 and SCC was 10.3%, 25.6% and 42.3% respectively in 78 ESCC patients preoperatively, so the sensitivity of these tumor markers was lower. One month after esophagectomy, serum Cyfra21-1 and serum SCC were significantly decreased compared to the preoperative level (P<0.01). However, there was no significant difference of preoperative serum CEA compared to a month after esophagectomy in ESCC (P>0.05). The specificity of HMGB1, CEA, Cyfra21-1 and SCC were 93.3%, 88.3%, 90.0% and 93.3% respectively. Compared to CEA, Cyfra21-1 and SCC, serum HMGB1 in ESCC patients is easier for detection and its sensitivity and specificity are higher, which may be used as a marker in diagnosis, prediction of prognosis and monitor of postoperative recurrence of ESCC.

Huang C.,Tohoku University | Niu K.,Tianjin Medical University | Momma H.,Tohoku University | Kobayashi Y.,Tohoku University | And 2 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2014

Background and aims: Increased levels of circulating adiponectin in the elderly cause a negative impact on physical function and health status, which suggests that circulating adiponectin may be related to skeletal muscle function. However, data on the relationship between circulating adiponectin levels and skeletal muscle function is limited. Our objective was to investigate the association between serum adiponectin levels and muscle strength in adults. Methods and results: This cross-sectional study is a part of the Oroshisho Study of adult employees in Japan from 2008 to 2011. In our study, we used data gathered in 2008-2010 that had included serum adiponectin measurements (n=1378; age, 19-83 years). From this population, 1259 subjects were evaluated for grip strength (949 men, 310 women), and 965 subjects were evaluated for leg extension power (716 men, 249 women). Multivariate linear regression analyses showed that adiponectin was associated significantly and negatively with both grip strength (β and standard error [SE]: men, -0.09 [0.01], p=0.010; women, -0.20 [0.03], kg, p=0.002) and leg extension power (men, -0.09 [0.02], p=0.014; women, -0.14 [0.07], W, p=0.032) after adjusting for age, physical activity, nutrient intake, depressive symptoms, metabolic syndrome, C-reactive protein, body mass index, and other lifestyle-related potential confounders. Conclusion: This population-based cross-sectional study indicates an inverse association between serum adiponectin levels and muscle strength in adults. Further studies are necessary to confirm this association and to clarify causality. © 2013 Elsevier B.V.

Shen X.,Nankai University | Li N.,Nankai University | Li H.,Tianjin Medical University | Zhang T.,University of Texas M. D. Anderson Cancer Center | Wang F.,University of Texas M. D. Anderson Cancer Center
Journal of Cancer Research and Clinical Oncology | Year: 2010

Background and purpose: Few detailed studies about the correlations among the expanded prevalence, elevated function of Treg cells in tumor microenvironment of hepatocellular carcinoma (HCC), and different clinical tumor stage were reported. The purpose of the present study was to examine the presence and functions of CD4+CD25high regulatory T cell (Treg cell) in tumor microenvironment from early and late stages and reveal the potential underlying mechanisms that may be responsible. Method: The prevalence of Treg in peripheral blood and fresh tissue samples from 31 patients with HCC after radical hepatectomy and 9 controls was detected. CD127 was selected as a Treg cell maker to test the cell populations and compared its expressions with ICOS. The expressions of FOXP3 mRNA were analyzed. The migration, proliferation, and suppression functions of Treg cell were observed. IFN-γ., IL-10, TGF-, CCL-17, CCL-22, and SDF-1 in cell supernatant were detected. Among all of the tests, the relations among the different TNM tumor stages, populations, and functions of Treg cells were evaluated. Results: The prevalence of Treg cell was significantly higher in the peripheral blood and in tumor tissue compared with those in normal donors. Increased numbers of Treg cell were showed in peripheral blood as well as in tumor tissue. High levels of IL-10 and TGF-, but little IFN-γ, were detected in the tumor microenvironment. Treg cells potently suppressed the functions and proliferation of CD4+CD25- T cells. High levels of SDF-1 were detected in malignant biopsies compared with those in benign regions, significantly increased in stage III. Plasma from the same patient was able to chemoattract Treg cell but that was lesser extent than those in tumor supernatant. Also, supernatant in advanced stage tumors exhibited powerful chemoattractic activity. SDF-1 played an important role in the recruited functions of Treg cell into tumor microenvironment of early and advanced stages. The expressions of Foxp3 mRNA increased in different TNM stages. The increased prevalence and expanded function of Treg cells in the tumor microenvironment of HCC were correlated with the cancer stage. Conclusion: The increase in frequency of Treg cells might play a role in modulation of the immune response against HCC in different TNM stages. The substance secreted in tumor microenvironment recruited CD4+CD25+ Treg cells to tumor sites to contribute to the prosperity and growth of the tumors. The performance of Treg cells in different TNM stages of tumor microenvironment might be acted as the route to evaluate the immunotherapy-based methods, promote therapy effect, and consequently to increase the survival rate in HCC. © 2010 Springer-Verlag.

Li X.X.,Tianjin Medical University
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2013

To detect the expression of Robo1 in lung cancer tissues, adjacent non-cancerous tissues as well as lung cancer brain metastasis, and explore the correlation of Robo1 expression to lung cancer brain metastasis. SP (streptavidin-peroxidase) staining method was used to examine the Robo1 expression in specimens from 80 cases of NSCLC, 52 cases of adjacent non-cancerous tissues and 72 cases of lung cancer with single brain metastasis (without metastasis in other organs). The Robo1 expression was further examined in 17 self control cases with lung cancer tissues and their brain metastasis tissues. The results were assessed by Kaplan-Meier analysis and log-rank test. The positive expression rate of Robo1 among adjacent non-cancerous tissues, lung cancers tissues and the lung cancer brain metastasis tissues were 1.9% (1/52), 13.8% (11/80) and 40.3% (29/72), respectively, and significant differences were detected among them (P < 0.05). During the 17 self control cases, the positive expression rate of Robo1 in lung cancer tissue and their brain metastasis tissues were 17.6% and 64.7%, respectively, with a significant difference between them (P < 0.01). Among the 72 cases of lung cancer brain metastasis, the median survival time of cases with positive Robo1 expression was 10 months, significantly shorter than that of cases with negative expression of Robo1 (17 months, P < 0.05). The positive expression rate of Robo1 was increased in sequence from the lowest in adjacent non-cancerous tissues, intermediate in the lung cancer tissues to highest in the lung cancer brain metastasis tissues. The expression of Robo1 in lung cancer brain metastasis is negatively correlated with the prognosis of patients with lung cancer brain metastasis. Robo1 may promote the genesis and progression of lung cancer and lung cancer brain metastasis as a cancer-promoting oncogene.

Cheng B.,Nankai University | Hou Y.,Nankai University | Wang L.,Nankai University | Dong L.,Tianjin Medical University | And 2 more authors.
Analytical and Bioanalytical Chemistry | Year: 2012

Traditional Chinese medicine (TCM) preparations have been used as an effective multitarget strategy for the treatment of complex diseases; however, their bioactive constituents are undefined and difficult to identify. In this study, a simple and dual-target method based on ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry combined with dual-bioactive (NF-κB and β2-adrenergic receptor) luciferase reporter assay systems was developed for the rapid determination of various bioactive compounds of TCM preparations. Qingfei Xiaoyan Wan, a TCM preparation used for the clinical therapy of asthma, was analyzed with this method. Potential anti-inflammatory and spasmolytic constituents were screened using NF-κB and β2- adrenergic receptor activity luciferase reporter assay systems and simultaneously identified according to the time-of-flight mass spectrometry data. One β2-adrenergic receptor agonist (ephedrine) and four structural types of NF-κB inhibitors (arctigenin derivatives, cholic acid derivatives, chlorogenic acid, and sinapic acid) were characterized. Tracheloside was considered a new NF-κB inhibitor. Further cytokine and chemokine detection confirmed the anti-inflammatory effects of the potential NF-κB inhibitors. The integration of ultraperformance liquid chromatography/quadrupole time-offlight mass spectrometry and dual-bioactive human cell functional evaluation systems proved to be a simple and effective strategy for the rapid screening of various bioactive compounds in TCM preparations used to treat complex diseases. © Springer-Verlag 2012.

To evaluate the clinical efficacy and safety of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) for patients with locally advanced non-small-cell lung cancer (LANSCLC). 48 patients with LANSCLC treated with SIB-IMRT from January 2010 to April 2012 were retrospectively analysed. A radiation dose of 45-63 Gy (median dose, 51.58 Gy) was delivered to the planning target volume (1.8-2.0 Gy daily fractions) simultaneously with 55.0-74.2 Gy (median dose, 63 Gy) to the planning gross tumour volume (2.00-2.25 Gy daily fractions). 45 patients received concurrent/sequential chemotherapy. The overall survival (OS), locoregional recurrence-free survival (LRFS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Treatment-related pneumonitis and oesophagitis were graded according to the Common Terminology Criteria for Adverse Events v. 4.0. By 1 July 2013, 29 of the 48 patients were dead. The median follow-up time for the survivors was 28 months (19-44 months). The median OS and PFS were 21 and 14 months, respectively. The median LRFS time was not reached. The 2-year LRFS, OS and PFS were 62.5%, 45.1% and 28.0%, respectively. Two patients experienced Grade 3 treatment-related pneumonitis, two patients experienced Grade 5 treatment-related pneumonitis and two patients had ≥Grade 3 oesophagitis. SIB-IMRT appears to be an effective therapeutic option in patients with LANSCLC and warrants further evaluation with increased number of patients in prospective clinical trials. This study explores the feasibility of delivering tumoricidal doses of radiation to primary lesions in non-small-cell lung cancer.

Meng H.M.,Tianjin Medical University
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2013

Pure epithelial breast metaplastic carcinoma is a rare and highly malignant tumor. In this study, our purpose was to analyze the clinical features, treatment method and prognostic factors, so to explore the approach for early diagnosis and appropriate treatment of this cancer. Clinical data of 22 patients with histopathologically confirmed pure epithelial breast metaplastic carcinoma and treated at Tianjin Cancer Hospital from 1974 to 2008, were reviewed retrospectively. Survival rate was calculated by life tables. Kaplan-Meier unvariate analysis and Log-rank test were used to compare the survival rates. Multivariate factors for survival were analyzed by Cox proportional hazards regression model. The median age of the 22 cases of pure epithelial breast metaplastic carcinoma was 52.5 years. Among them 20 cases went to see a doctor for painless mass, and two cases shown as skin inflammation. Clarifying a diagnosis was difficult before operation so that its diagnosis mainly depended on postoperative histopathologic examination. Twelve cases had axillary lymph node metastasis, 7 cases distant metastasis, and the lung was the most common metastatic organ. The 5-year survival rate was 55.6%, with a median follow-up of 46 months. It was found by Kaplan-Meier unvariate analysis that the age (P = 0.044), number of positive axillary lymph nodes (P = 0.011) and therapeutic schedule (P = 0,003) significantly influenced the outcome of the patients, but tumor size (P = 0.194) was not. Cox multivariate analysis results showed that number of positive axillary lymph nodes was independent prognostic factor for pure epithelial breast metaplastic carcinoma (P = 0.038). Pure epithelial breast metaplastic carcinoma is seldom seen. It is easy to cause distant metastasis and has a poor prognosis. ER, PR and HER-2 expressions in most samples are negative. The more axillary lymph nodes have metastasis, the poorer is the prognosis. A reasonable and comprehensive treatment can improve the prognosis obviously.

Qin X.L.,Tianjin Medical University
Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases | Year: 2012

To identify suitable hydroxyl polycyclic aromatic hydrocarbons (OH-PAHs) for co-evaluation of internal exposure level of PAHs by simultaneous determination of a variety of OH-PAHs in urine. The 24-h individual particulate matter and morning urine samples of 112 subjects were collected during June 2011. PAHs carried by individual particulate matter samples and OH-PAHs in urine samples were detected by gas chromatography-mass spectrometry. Seven OH-PAHs were detected in urine samples, among which 1-hydroxy-naphthalene (1-OHNap) concentration was the highest [(20.54 ± 28.94) μmol/mol Cr], while 1-hydroxy-pyrene (1-OHP) concentration was the lowest [(0.73 ± 0.63) μmol/mol Cr]. The concentrations of these seven OH-PAHs decreased in the following order: 1-hydroxy-naphthalene (1-OHNap) > 9-hydroxy-fluorene (9-OHFlu) > 2-hydroxy-naphthalene (2-OHNap) > 3-hydroxy-fluorene (3-OHFlu) > 2-hydroxy-fluorene (2-OHFlu) > 6-hydroxy-chrysene (6-OHChr) > 1-hydroxy-pyrene (1-OHP). The effects of gender and smoking upon the contents of OH-PAHs in urine samples were not significant. There was a good correlation between total hydroxy-naphthalene (ΣOHNap) and 1-OHNap (r = 0.948), and a good correlation was also showed between total hydroxy-fluorene (ΣOHFlu) and 9-OHFlu (r = 0.975). Naphthalene carried by atmospheric particulate matters demonstrated better correlation with 1-OHNap than 2-OHNap, while fluorene carried by atmospheric particulate matters showed better correlation with 9-OHFlu than 3-OHFlu and 2-OHFlu. The correlation coefficients of ΣOHNap, ΣOHFlu and 6-OHChr with 1-OHP were 0.427, 0.543 and 0.655, respectively, and the correlations were not strong. It cannot reflect internal exposure level of PAHs to use 1-OHP as the only biomarker, while 1-OHNap and 9-OHFlu can be well predictive of the exposure levels of corresponding total OH-PAHs, suggesting that simultaneous determination of 1-OHNap, 9-OHFlu and 1-OHP can be more accurate and comprehensive in evaluating the internal exposure level of PAHs.

Jiao X.G.,Tianjin Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2013

To evaluate the clinicopathologic characteristics and prognosis of mixed histological type (MHT) gastric cancer. Clinical and follow-up data of 1108 gastric cancer patients undergoing radical operation in Tianjin Cancer Hospital between 2003 and 2006 were analyzed retrospectively. Clinicopathologic characteristics of MHT gastric cancer were summarized and the prognosis was analyzed by Kaplan-Meier analysis and COX regression. Among the 1108 patients, 144 (13.0%) had mixed histology type of gastric cancer. Compared to the unitary histological type (UHT), MHT gastric cancer had bigger tumor size, higher proportion of T4 tumor, and was easier for lymph node and distant metastasis (all P<0.05). The 3- and 5-year survival rates of patients with MHT were 26.5% and 10.8% respectively, which were lower than those with UHT (58.8% and 35.0%, P<0.01). Univariate and multivariate analyses showed TNM classification was an independent prognostic factor (P<0.01). MHT gastric cancer shows worse prognosis than UHT gastric cancer. There is no difference in prognosis among various combination of MHT gastric cancer. TNM classification is an independent prognostic factor of MHT gastric cancer.

Liu H.G.,Tianjin Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2013

To evaluate the prognostic value of metastatic lymph node ratio (MLR) for gastric cancer patients with less than 15 lymph nodes dissected. Clinical data of 610 gastric cancer patients undergoing operation in Tianjin Cancer Hospictal from January 2003 to July 2007 were analyzed retrospectively. Patients were divided into two groups: <15 lymph nodes dissected group (n=320) and ≥ 15 lymph nodes dissected group (n=290). MLR was classified based on the following intervals: rN1 ≤ 10%, rN2 10%-30%, rN3 30%-60% and rN4 >60%. Survival was determined by Kaplan-Meier method and difference was assessed by Log-rank test. Multivariate analysis was performed using Cox proportional hazard regression model. Survival rates were compared between two groups in pN and rN stages respectively. In <15 nodes group, all the survival differences among various rN stages were not significant (all P>0.05), while in same rN stage, all the survival differences among various pN stages were not significant (all P>0.05). Significant differences of 5-year cumulative survival rates were found between the two groups in pN2 and pN3a stage patients (both P<0.05) while no significant differences were found among different rN stages (all P>0.05). Multivariate analysis demonstrated rN stage was an independent prognostic factor for gastric cancer patients with <15 lymph nodes dissected (P=0.012, RR=1.617, 95%CI:1.111-2.354). The rN staging system based on MLR can predict the prognosis of gastric cancer patients with less than 15 lymph nodes dissected.

Zhang H.,Tianjin Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2013

To investigate the clinicopathological characteristics and prognostic factors of bone metastasis in gastric cancer patients. Clinicopathological data of 66 gastric cancer patients with bone metastasis, who were treated at the Tianjin Medical University Cancer Institute and Hospital from October 1997 to September 2011, were analyzed retrospectively. The clinicopathological characteristics of the primary cancer and bone metastasis were summarized and the prognosis was analyzed. Of 66 patients, 4 underwent operation, 28 chemotherapy, 32 inhibitors of bone resorption,8 local treatment and 23 symptomatic treatment alone. The median survival time of these 66 patients was 5 months (95%CI:3.3-6.7 months). The 1-, 2- and 3-year survival rates were 9.1%, 3.0% and 1.5%, respectively. Univariate Log-rank test indicated that gender, bone metastasis combined with other distant metastasis and chemotherapy were significant prognostic factors (all P<0.05). Multivariate analysis revealed bone metastasis combined with other distant metastasis was an independent prognostic factor (P=0.011, RR=2.067, 95%CI:1.178-3.626). Prognosis of patients with bone metastasis from gastric cancer is poor. Chemotherapy-based comprehensive treatment may improve the prognosis of these patients.

Jiao X.G.,Tianjin Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2013

To evaluate the feasibility and necessity of No.13 lymph node dissection in D2 radical gastrectomy for lower-third advanced gastric cancer (AGC). Data of 379 cases who were diagnosed as TNM II-III stage AGC were collected from January 2001 to June 2007. One hundred cases who undergone No.13 lymph node dissection during D2 gastrectomy for lower-third AGC were selected as study group. Other 279 cases (control group) received only D2 gastrectomy. The differences in clinicopathologic and intraoperative and postoperative parameters and 5-years survival rate were compared using the SPSS 17.0 software. There were no significant differences between the two groups in patients' gender, age, tumor size, histologic type, Borrmann type, duodenum invasion, tumor depth, lymph node metastasis, TNM classification, operative time, blood loss and the incidence of postoperative complications (P > 0.05). In the study group, there were 9 patients with positive No. 13 lymph node, and its 5-year survival rate (46.0%) was higher than the control group (36.5%, χ2 = 4.452, P < 0.05). The Univariate analysis showed that age (χ2 = 7.539), No.13 lymph node dissection (χ2 = 4.452), tumor size (χ2 = 7.100), duodenum invasion (χ2 = 9.106), tumor depth (χ2 = 7.428), lymph node metastasis (χ2 = 45.046), TNM classification (χ2 = 57.008) are associated with prognosis of lower-third AGC (P < 0.05). Multivariate analysis identified age (HR = 0.500, 95% CI: 0.343 - 0.730), tumor size (HR = 0.545, 95%CI: 0.339 - 0.876), duodenum invasion (HR = 5.821, 95%CI: 2.326 - 14.572), and tumor depth (T4: HR = 2.087, 95% CI: 1.283 - 3.394) as independent prognostic factors (P < 0.05). No. 13 lymph node dissection for TNM II-III stage lower-third advanced gastric cancer is feasible and necessary.

Liu D.Y.,Tianjin Medical University
Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi | Year: 2013

Male breast cancer (MBC) is a rare disease, with clinical and prognostic features still controversial. The aim of this study was to discuss the clinical characteristics and prognosis of MBC. Clinical data related to 71 MBC patients was reviewed. The radio of MBC to female breast cancer (FBC) was 42:10 000. Age related to the diagnosis of MBC ranged from 43 to 84 years with the median age as 62 years old, older than the FBC patients (t = 6.355, P = 0.000). The percentage of invasive ductal carcinoma in MBC patients was much higher than in FBC patients (χ(2) = 29.875, P = 0.000). The positive rate of estrogen receptor (ER) was significantly higher than those in FBC patients and the positive rates of human epidermal growth factor receptor-2 (HER-2) were less frequently (χ(2) = 3.741, P = 0.048 and χ(2) = 12.845, P = 0.002) seen. Data from the univariate and multivariate analysis showed that the 3-, 5- and 10-year survival rates of MBC were 82.6%, 74.0% and 47.4% respectively, significantly higher than those in FBC patients (P = 0.004, P = 0.046). Patients with positive HER-2 showed worse prognosis than HER-2 negative patients in MBC patients (χ(2) = 4.219, P = 0.040). There were significant clinic-pathologic and prognostic differences between FBC and MBC patients. The HER-2 positivity seemed to be an important factor for the prognosis and treatment of patients with MBC.

Wang W.,Tianjin Medical University
Journal of experimental & clinical cancer research : CR | Year: 2010

BACKGROUND: Survival of laryngeal squamous cell carcinoma (LSCC) patients has remained unchanged over recent years due to its uncontrolled recurrence and local lymph node metastasis. Vasculogenic mimicry (VM) is an alternative type of blood supplement related to more aggressive tumor biology and increased tumor-related mortality. This study aimed to investigate the unique role of VM in the progression of LSCC. METHODS: We reviewed clinical pathological data of 203 cases of LSCC both prospectively and retrospectively. VM and endothelium-dependent vessel (EDV) were detected by immunohistochemistry and double staining to compare their different clinical pathological significance in LSCC. Survival analyses were performed to assess their prognostic significance as well. RESULTS: Both VM and EDV existed in LSCC type of blood supply. VM is related to pTNM stage, lymph node metastasis and pathology grade. In contrust, EDV related to location, pTNM stage, T stage and distant metastasis. Univariate analysis showed VM, pTNM stage, T classification, nodal status, histopathological grade, tumor size, and radiotherapy to be related to overall survival (OS). While, VM, location, tumor size and radiotherapy were found to relate to disease free survival (DFS). Multivariate analysis indicated that VM, but not EDV, was an adverse predictor for both OS and DFS. CONCLUSIONS: VM existed in LSCC. It contributed to the progression of LSCC by promoting lymph node metastasis. It is an independent predictors of a poor prognosis of LSCC.

To investigate gene mutations of epidermal growth factor receptor (EGFR) and K-ras in Chinese patients with non-small cell lung cancer (NSCLC) and its clinicopathological significance, and to analyze the correlation between these mutations and tumor response to erlotinib treatment. Mutations of exons 18, 19, 20 and 21 of the EGFR and codons 12, 13 of the K-ras in 301 cases of NSCLC were detected by PCR-amplification and gene sequencing. The relationship between the mutations and clinicopathological characteristics of the 301 patients was analyzed. EGFR mutations were present in 32.9% (99/301) of the samples: 3 mutation in exon 18, 59 in exon 19, 2 in exon 20, and 35 in exon 21. Mutations of K-ras were present in 4.7% (14/301) of the samples: 13 in codon 12 and 1 in codon 13. EGFR mutations were never found in tumors with K-ras mutations, suggesting a mutually exclusive relationship. EGFR mutations were more common in adenocarcinomas, non-smokers and females. Seven out of 10 erlotinib-treated patients with disease control carried EGFR mutation. The frequency of EGFR mutation in Chinese NSCLC patients is higher than that in Westerners, but the frequency of K-ras mutation is quite opposite. Combined detection of EGFR gene and K-ras gene mutation may help clinicians to choose patients who may gain benefit from EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment, and to predict their response to erlotinib treatment and prognosis.

Liu H.G.,Tianjin Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2013

To investigate the impact of tumor size in the prognosis of T4a stage gastric cancer. The best cut-off point depending on tumor size was selected by Kaplan-Meier. Compare cliniclópathological characteristics between small size gastric cancer (SSG) and large size gastric cancer (LSG). Univariate analysis was done by Log-rank test and multivariate analysis was performed using the Cox proportional hazard regression model. The independent prognostic factors of patients were performed subgroup analysis. Eight centimetre was the optimal cut-off of tumor size for T4a stage gastric cancer. There were significantly differences between SSG and LSG in tumor location (χ2 = 15.695), histological grade (χ2 = 4.393), macroscopic type (χ2 = 5.629) and early recurrence (χ2 = 4.292). Univariate analysis showed age (χ2 = 4.463), tumor size (χ2 = 9.057), macroscopic type (χ2 = 6.679), histological grade (χ2 = 5.122), location of tumor (χ2 = 8.707) and N stage (χ2 = 132.954) are related to survival (P < 0.05). Among them, tumor size (HR = 1.339), histological grade (HR = 1.169) and N stage (HR = 1.876) were independent risk factor for survival (P = 0.05). For SSG, N stage (HR = 2.014) and histological grade (HR = 1.192) were independent risk factor for survival (P = 0.05), and for LSG, N stage (HR = 1.876) was independent risk factor for survival (P = 0.000). Further stratified analysis indicated that the 5-year survival rate of LSG is significantly lower than that of SSG in T4a stage patients of gastric cancer without lymph nodes metastasis or poorly differentiated (HR = 0.182 and 0.653, P < 0.01). Tumor size is an independent prognostic factor in patients of T4a stage gastric cancer. Tumor size cut-off point of 8 cm can exert significant impact on the prognosis of T4a stage gastric cancer without lymph nodes metastasis or poorly differentiated.

Zhang H.D.,Tianjin Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2013

To compare the prognostic value of AJCC/UICC pN stage with metastatic lymph node ratio (MLR) and the prognostic difference between the tumor-node-metastasis (TNM) stage and tumor-ratio-metastasis (TRM) stage in patients with adenocarcinoma of the gastroesophageal junction. Clinical data of 414 patients with adenocarcinoma of the gastroesophageal junction undergoing curative resection at the Tianjin Medical University Cancer Institute and Hospital from January 2000 to June 2007 were retrospectively reviewed. Spearman correlation analysis was performed to examine the correlations between pN, MLR and retrieved nodes. Univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis were performed to analyze the effects of pN, MLR, TNM and TRM stage on the prognosis of these patients. The area under the ROC curve (AUC) was plotted to compare the value of these stages and to predict the 5-year survival rate. The median number of retrieved nodes was 17 (4-71) per patient, and the median number of positive nodes was 4 (0-67) per patient. The number of metastatic lymph node was positively correlated with that of retrieved nodes (P<0.01), but MLR was not correlated with the number of retrieved nodes (P>0.05). Univariate and multivariate survival analysis showed that either pN or MLR could be used as an independent risk factor for survival (P<0.01) and the hazard ratio of MLR stage was larger than that of pN stage (1.573 vs 1.382). While pN and MLR were entered into the Cox hazard ratio model as covariates at the same time, MLR remained as the independent prognostic factor (P<0.01), but pN lost significance (P>0.05). The AUC of MLR and pN staging was 0.726 and 0.714, and of TRM and TNM staging was 0.747 and 0.736, respectively, however the differences were not statistically significant (all P>0.05). MLR is an independent prognostic factor for patients with adenocarcinoma of the gastroesophageal junction. The value of MLR and TRM staging systems may be superior to pN and TNM staging systems in evaluating the prognosis of these patients.

Choi S.Y.C.,BC Cancer Agency | Choi S.Y.C.,Vancouver Prostate Center | Lin D.,BC Cancer Agency | Lin D.,Vancouver Prostate Center | And 7 more authors.
Advanced Drug Delivery Reviews | Year: 2014

The development of novel cancer therapeutics is often plagued by discrepancies between drug efficacies obtained in preclinical studies and outcomes of clinical trials. The inconsistencies can be attributed to a lack of clinical relevance of the cancer models used for drug testing. While commonly used in vitro culture systems are advantageous for addressing specific experimental questions, they are often gross, fidelity-lacking simplifications that largely ignore the heterogeneity of cancers as well as the complexity of the tumor microenvironment. Factors such as tumor architecture, interactions among cancer cells and between cancer and stromal cells, and an acidic tumor microenvironment are critical characteristics observed in patient-derived cancer xenograft models and in the clinic. By mimicking these crucial in vivo characteristics through use of 3D cultures, co-culture systems and acidic culture conditions, an in vitro cancer model/microenvironment that is more physiologically relevant may be engineered to produce results more readily applicable to the clinic. © 2014 The Authors.

Liu H.G.,Tianjin Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2013

To evaluate the value of negative lymph node count (NLNC) in prediction of prognosis of advanced gastric cancer after radical resection. The 544 cases of radical gastrectomy patients with complete clinical and follow-up data between January 2011 and July 2007 were collected. Survival was determined by the Kaplan-Merier method and univariate analysis was done by Log-rank test, Multivariate analysis was performed using the Cox proportional hazard regression model. Univariate analysis showed age (χ(2) = 4.449), T stage (χ(2) = 30.482), N stage (χ(2) = 205.452), location of tumor (χ(2) = 16.649), tumor size (χ(2) = 35.117), macroscopic type (χ(2) = 4.750), histological grade (χ(2) = 6.130), NLNC stage (χ(2) = 150.369) and type of gastrectomy (χ(2) = 25.605) were related to survival. Among them, T stage, N stage, tumor size and NLNC stage were independent risk factors for survival (P < 0.05). The prognostic factors of patients were performed subgroup analysis, NLNC > 15 group can prolong the survival than NLNC ≤ 15 group in the T2 stage (HR = 0.315), T4 stage (HR = 0.401), the same classification of location of tumor (HR = 0.286-0.493), tumor size (HR = 0.336, 0.465), macroscopic type (HR = 0.306, 0.418), histological grade (HR = 0.411, 0.365) and type of gastrectomy (HR = 0.444, 0.358 and 0.356, all P < 0.05). More NLNC can prolong Disease-Free Survival for patient of early recurrence (χ(2) = 8.648, P = 0.003). Sufficient negative lymph node count can prolong the survival and decrease the risk of early recurrence.

Zhang C.-H.,Tianjin Medical University | Zhang C.-H.,Anhui Medical University | Xu G.-L.,Anhui Medical University | Jia W.-D.,Anhui Medical University | And 3 more authors.
International Journal of Cancer | Year: 2011

Available literature on the effects of interferon (IFN) treatment on development and progression of hepatocellular carcinoma (HCC) in patients with chronic virus infection reports controversial results. The primary objective of this meta-analysis was to evaluate the effect of IFN on HCC risk in patients with chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection; IFN's efficacy on local tumor progression and survival of advanced HCC patients was also assessed. All randomized controlled trials (RCTs) comparing IFN with no antiviral treatment were selected. Finally, we identified 11 RCTs including 1,772 patients, who met our inclusion criteria to perform this meta-analysis. Our analysis results showed that IFN significantly decreased the overall HCC incidence in HCV-infected patients [relative risk (RR) = 0.39; 95% confidence interval (CI) = 0.26-0.59; p = 0.000], subgroup analysis indicated that IFN decreased HCC incidence in HCV-related cirrhotic patients evidently (RR = 0.44; 95% CI = 0.28-0.68; p = 0.000); but HCC incidence in nonresponders to initial antiviral therapy did not reduce by maintenance IFN therapy (RR = 0.96; 95% CI = 0.59-1.56; p = 0.864). Analysis results also demonstrated that IFN did not significantly affect the overall rate of HCC in HBV-infected patients although there was a trend favoring IFN therapy (RR = 0.23; 95% CI = 0.05-1.04; p = 0.056). Besides, IFN did not improve one-year overall survival of advanced HCC patients significantly (RR = 1.61; 95% CI = 0.96-2.69; p = 0.072); however, a quantitative analysis on local tumor progression could not be performed owing to lack of unified definitions among trials included in our study. By this meta-analysis, we conclude that IFN therapy is effective in reducing overall HCC risk in chronic HCV-infected patients; using it in this subpopulation seems promising, but its administration in other subpopulations still requires further exploration. Copyright © 2010 UICC.

Yang D.,Tianjin Medical University | Yang D.,Wuhan University | Jia R.,Wuhan University | Tan J.,Tianjin Medical University
Journal of Nephrology | Year: 2013

Background: Intracellular Ca2+ overload is considered to be a key factor in contrast-induced acute kidney injury (CI-AKI). The Na+/Ca2+ exchanger (NCX) system is one of the main pathways of intracellular Ca2+ overload. We investigated the effects of KB-R7943, an inhibitor of the reverse mode of NCX, on CI-AKI in a rat model. Method: Rats were divided into control group, CI-AKI group and pretreatment groups (with KB-R7943 dose of 5 or 10 mg/kg). CI-AKI was induced by diatrizoate administration in rats with cholesterol-supplemented diet for 8 weeks. Renal function and renal hemodynamics were determined 1 day following contrast medium administration. Renal histopathology was observed by light microscope. Renal tubular apoptosis was examined by TUNEL. Renal endothelin-1 (ET-1) was measured by radioimmunoassay. Renal malondialdehyde (MDA) and catalase (CAT) were measured as oxidative markers. Results: Levels of serum creatinine (Scr), renal ET-1, MDA and CAT, and resistance index (RI) of renal blood vessels increased significantly in CI-AKI rats. The increases in Scr and RI of renal blood vessels induced by diatrizoate were suppressed significantly and dose-dependently by pretreatment with KB-R7943. Histopathological and TUNEL results showed that the contrast medium-induced severe renal tubular necrosis and apoptosis were significantly and dosedependently attenuated by KB-R7943. KB-R7943 significantly suppressed the increment of renal ET-1 content and MDA and CAT level induced by contrast medium administration. Conclusion: Activation of the reverse mode of NCX, followed by ET-1 overproduction and increased oxidative stress, seems to play an important role in the pathogenesis of CI-AKI. The inhibitor of the reverse mode of NCX, KB-R7943, has renoprotective effects on CI-AKI. © 2013 Società Italiana di Nefrologia.

Goudis C.A.,General Hospital of Grevena | Korantzopoulos P.,University of Ioannina | Ntalas I.V.,University of Ioannina | Kallergis E.M.,University of Crete | And 2 more authors.
International Journal of Cardiology | Year: 2015

Diabetes mellitus (DM) represents one of the most important risk factors for atrial fibrillation (AF) while AF is a strong and independent marker of overallmortality and cardiovascularmorbidity in diabetic patients. Autonomic, electrical, electromechanical, and structural remodeling, including oxidative stress, connexin remodeling and glycemic fluctuations seemto be implicated in AF pathophysiology in the setting of DM. The present reviewhighlights the association between DMand AF, provides a comprehensive overview of the responsible pathophysiological mechanisms and briefly discusses potential upstream therapies for DM-related atrial remodeling. © 2015 Elsevier Ireland Ltd. All rights reserved.

Wang X.S.,University of Texas M. D. Anderson Cancer Center | Cleeland C.S.,University of Texas M. D. Anderson Cancer Center | Mendoza T.R.,University of Texas M. D. Anderson Cancer Center | Yun Y.H.,National Cancer Center | And 3 more authors.
Journal of the National Cancer Institute | Year: 2010

Background: Patient reporting of the severity and impact of symptoms is an essential component of cancer symptom management and cancer treatment clinical trials. In multinational clinical trials, cultural and linguistic variations in patient-reported outcomes instruments could confound the interpretation of study results. Methods: The severity and interference of multiple symptoms in 1433 cancer patients with mixed diagnoses and treatment status from the United States, China, Japan, Russia, and Korea were measured with psychometrically validated language versions of the M. D. Anderson Symptom Inventory (MDASI). Mixed-effect ordinal probit regression models were fitted to the pooled data to compare the magnitude of the effect of "country" (nation and linguistic factors) with between-subjects effects on symptom reporting, adjusted for patient and clinical factors (age, sex, performance status, and chemotherapy status). Results: For the pooled sample, fatigue, disturbed sleep, distress, pain, and lack of appetite were the most severe patient-reported MDASI symptoms. The magnitude of the variance of the country random effects was only one-fourth to one-half of the interpatient variation (σ2 = 0.23-0.46) for all symptoms, except nausea and vomiting. Conclusions: Cultural and linguistic variations in symptom reporting among the five language versions of the validated MDASI were limited. Ordinal probit modeling provided a simple mechanism for accounting for cultural and linguistic differences in patient populations. The equivalence among MDASI translations in this study suggests that symptom ratings collected from various cultural and language groups using the MDASI can be interpreted in a similar way in oncology practice, clinical trials, and clinical research. © The Author 2010. Published by Oxford University Press. All rights reserved.

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

To analyze the relationship between hepatitis B virus (HBV) precore (PC) and basal core promoter (BCP) mutations and HBV-related acute-on-chronic liver failure (HB-ACLF). Forty-four patients with HB-ACLF and 28 patients with chronic hepatitis B (CHB; used as controls) were enrolled and venous blood samples were collected from all individuals. The PC and BCP gene fragments were amplified by nested PCR. HBV genotype and BCP/PC mutations were determined by direct sequencing and analysis by BioEdit (version Ten of the HB-ACLF patients were selected for follow-up (range: 2-8 weeks), which included once weekly sera collection to determine the relation of mutations and treatment response. Serum levels of HBV DNA were measured by real-time PCR assay, and alanine aminotransferase, total bilirubin, creatinine and albumin were measured by standard biochemical assay and used to determine the MELD score. All 44 HB-ACLF patients were infected with HBV genotype C. In the CHB group, 26 patients were infected with genotype C and two with genotype B. Single mutations (A1762T, G1764A, T1753V, G1896A, and G1899A) and combined mutations (A1762T + G1764A, G1896A + G1899A, T1753V+ A1762T + G1764A, G1896A + G1899A + A1762T + G1764A, and A1762T + G1764A + G1896A) were more frequently detected in HB-ACLF patients than in CHB patients (P less than 0.05). A significantly higher proportion of PC/BCP wild-type sequences was found in patients with CHB than in patients with HB-ACLF (17.9% vs. 2.3%; x2 = 5.440, P = 0.020). The proportion of patients carrying both PC and BCP mutations was significantly higher in HB-ACLF patients than in CHB patients (79.6% vs. 39.3%; x2 = 12.021, P = 0.001). The proportion of patients carrying only BCP mutation was 42.9% in the CHB group and 20.5% in the HB-ACLF group (x2 = 4.157, P = 0.041). No occurrences of only PC mutation were detected in either the CHB or HB-ACLF group. The combined mutations were present in all 10 of the HB-ACLF follow-up patients. Mutations G1899A, T1753V, and A1846T were correlated with disease recovery. Significant decreases in the MELD score were accompanied by decreases in the A1846T mutation. Significantly more HB-ACLF patients carried HBV with mutations in the PC and BCP than CHB patients. Moreover, more HB-ACLF patients carried HBV with PC + BCP combined mutations and PC mutation only. The G1899A, T1753C, and A1846T mutations were associated with HB-ACLF response to treatment and improvement in liver function.

Zhang L.M.,Tianjin Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2010

To analyze the clinical conditions of postoperative patients with IIIA-N2 non-small cell lung cancer (NSCLC) and the prognostic factors related with survival of NSCLC, and to investigate the influence of operation and therapy on prognosis. Clinical data of 657 inpatient cases with IIIA-N2 NSCLC admitted from January 2000 to December 2005 was retrospectively reviewed. The Kaplan-Meier method was used for survival analysis. The Log-rank law was applied to analyze the relationship between the variables and the prognosis in monovariate analysis, while Cox proportional hazard regression model was used to make multivariate analysis. The 1-, 3-and 5-year accumulative survival rates of the operative patience were 64.4%, 26.0% and 17.9%, respectively. The median survival time was 18 months. In monovariate analysis, the main unfavorable factors that affect life span involve were the diameter of tumor, T stage, skip metastasis of N2 lymph node, the number of metastatic lymph nodes, the metastasis of subcarinal lymph nodes, adjuvant chemotherapy, the cycle of adjuvant chemotherapy, postoperative radiotherapy, and the modality of therapy (the effect of naive surgery was disappointed, while the prognosis of the patients with adjuvant chemoradiotherapy was better than those with chemotherapy alone). A multivariate analysis using Cox regression identified 5 factors of prognosis: the diameter of tumor (P = 0.001), the metastasis of subcarinal lymph nodes (P = 0.019), the number of metastatic lymph nodes (P = 0.006), the cycle of adjuvant chemotherapy (P = 0.007), postoperative radiotherapy (P = 0.055), and adjuvant chemoradiotherapy (P = 0.026). The 5-year survival rate of the patients with IIIA-N2 Non-small cell lung cancer is poor. Tumor size, the metastasis of subcarinal lymph nodes, the number of metastatic LNs, the cycle of adjuvant chemotherapy, and postoperative radiotherapy have an effect on the prognosis. The prognosis of postoperative patients with single-level N2 and multi-level N2 disease is similar, and the key point of survival is the number of nodes involved. The therapeutic effect of patience given adjuvant chemoradiotherapy is superior to those treated with adjuvant chemotherapy.

Wu L.L.,Tianjin Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2010

To explore the pattern of lymph node metastasis(LNM) in advanced proximal gastric cancer in order to guide lymphadenectomy. Between September 2001 and December 2005, a total of 103 patients with advanced proximal gastric cancer underwent radical gastrectomy with D2 or>D2 lymphadenectomy. The clinical characteristics, pathologic features, and LNM were analyzed by univariate and multivariate analysis. LNM was observed in 81 of 103 cases(78.6%). The LNM was identified in 70.8% at N1, 38.3% at N2, 22.3% at N3. LNM frequency was found in groups No.3,No.1,No.2 and No.4Sa,4Sb (from the highest to the lowest) at N1, groups No.7, No.10, No.9, No.11, No.8a and No.4d at N2, and groups No.5, No.6, No.16 and No.12 at N3. Ordinal Logistic regression analysis showed that histopathological type, tumor size, depth of invasion, and distant metastasis were independent factors for lymph node metastasis in advanced proximal gastric cancer. The number of lymph node metastasis in advanced proximal gastric cancer is mainly associated with differentiation, tumor size, depth of invasion, and distant metastasis. It is essential to dissect the lymph nodes according to the risk of lymph node metastasis.

Shen X.,Tianjin 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 summarize the characteristic imaging signs of ossification of the ligamentum flavum (OLF) associated with dural adhesions by analyzing retrospectively the imaging signs of OLF associated with dural adhesions. A retrospective analysis was made on clinical data of 85 patients undergoing OLF surgery between January 2010 and September 2012. The patients were assigned into the study group and the control group according to the preoperative imaging signs. Of 85 patients, 34 had both "tram track sign" and "jagged line sign" as the study group and 51 had either "tram track sign" or "jagged line sign" and neither of them as the control group. Adherence between dura mater and ligamentum flavum was observed during operation as the "gold standard" for the diagnosis of dural adhesion. The imaging information of CT and MRI in sagittal and axial planes was analyzed. The typical characteristics of dural adhesions were found. Then the sensitivity, specificity, and positive likelihood ratio of the preoperative imaging examinations were calculated to estimate the reference value and diagnostic value (> 5 having reference value, and > 10 having diagnostic value). In the study group, dural adhesion was observed in 26 patients (10 males and 16 females), and the other 8 patients (6 males and 2 females) had no dural adhesion. In the control group, dural adhesion was found in 2 female patients who had "jagged line sign", and 49 patients had no dural adhesion (14 males and 35 females). In patients having both "tram track sign" and "jagged line sign", the sensitivity was 92.9%; the specificity was 86.0%; and the positive likelihood ratio was 6.6. In patients having "tram track sign", the sensitivity was 92.9%; the specificity was 64.9%; and the positive likelihood ratio was 2.6. In patients having "jagged line sign", the sensitivity was 100%; the specificity was 77.2%; and the positive likelihood ratio was 4.4. For patients with OLF having both "tram track sign" and "jagged line sign", preoperative CT and MRI have a reference value for diagnoses of the OLF associated with dural adhesions.

to investigate the activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) signaling pathway in the endometrium of women with polycystic ovary syndrome (PCOS) and its effect and significance in the cause of hyperplasia and carcinoma; and investigate the factors which affect the activation of the MAPK/ERK signaling pathway. collected 52 patients diagnosed as PCOS who were taken dilation and curettage of uterus as study, while 32 non-PCOS patients matched as control group. Serum hormonal parameters, fasting blood glucose and insulin were measured in all patients. The PCOS patients were sub-group as insulin resistance group and non-insulin resistance group; all the patients were carried out pathology inspection of endometria, and the PCOS patients were sub-group as endometrial hyperplasia and carcinoma group and normal endometrium group based on the outcome of pathology inspection. Western blot were performed to detect the expressions of ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2), the activation of ERK1/2. (1) the expression of p-ERK1/2 [(61 ± 13)%] in the endometrium in PCOS group was higher than that in the control [(44 ± 10)%, P < 0.01]. (2) The expression of p-ERK1/2 was significantly increased in group of endometrial hyperplasia and carcinoma [(70 ± 11)%] compared to that in group of normal endometrium [(55 ± 10)%, P < 0.01], while there were significant difference between group of insulin resistance [(63 ± 13)%] and group of non-insulin resistance [(55 ± 7)%, P < 0.01]. (3)Fasting insulin level, insulin area under the curve and body mass index were related to the expression of p-ERK1/2 in endometrium with PCOS, the correlation coefficient were 0.447, 0.456 and 0.381, respectively (all P < 0.01). the MAPK/ERK signaling pathway in endometrium with PCOS was overactivation, which was related to the endometrial hyperplasia and carcinoma; while the activation of MAPK/ERK signaling pathway were effected by insulin resistance and hyperinsulinemia.

Liu G.,Shandong University | Su L.,Shandong University | Hao X.,Shandong University | Zhong N.,Shandong University | And 3 more authors.
Journal of Cellular and Molecular Medicine | Year: 2012

Sirtuins (a class III histone deacetylase) have emerged as novel targets for cancer therapy. Salermide, a reverse amide compound that inhibits Sirtuin 1 (Sirt1) and Sirtuin 2 (Sirt2), has been shown to induce apoptosis in human cancer cells. The mechanism underlying cellular apoptotic signalling by salermide remains unclear. In this study, we show that salermide up-regulates the expression of death receptor 5 (DR5) in human non-small cell lung cancer (NSCLC) cells. Blocking DR5 expression by gene silencing technology results in a decrease in activated forms of several pro-apoptotic proteins (caspase-8, caspase-9, caspase-3, PARP). Increasing DR5 protein expression correlates with salermide-induced apoptosis in human NSCLC cells. We discovered that IRE-1α, Bip, activating transcription factor 3 (ATF4), activating transcription factor 3 (ATF3) and C/EBP homologous protein (CHOP) are induced by salermide, which suggests that DR5-dependent apoptosis is induced by endoplasmic reticulum stress. Moreover, knockdown of Sirt1 and Sirt2 expression resulted in up-regulation of ATF4, CHOP and DR5. Transfected NSCLC cells with ATF4, ATF3 or CHOP siRNA results in a decline in pro-apoptotic proteins (such as caspase-8, caspase-9, caspase-3 and PARP) despite salermide treatment. We demonstrate that salermide induces expression of ATF4, and ATF4 up-regulates ATF3 and subsequently modulates CHOP. This suggests that DR5 is modulated by the ATF4-ATF3-CHOP axis in NSCLC after Sirt1/2 inhibition or salermide treatment. This study highlights the importance of DR5 up-regulation in apoptosis induced by Sirt1/2 inhibition and elucidates the underlying mechanism in human NSCLC cells. © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Yang P.,Shaanxi Normal University | Yang P.,Duke University | Zhang X.,Tianjin Medical University
Chemical Communications | Year: 2012

In Nature, certain organisms can perform microbial corrosion on base metals by oxidation of neutral metallic atoms (H. L. Ehrlich, Appl. Microbiol. Biotechnol., 1997). Herein we describe the first discovery of biological nucleic acids able to catalyze and mediate gold oxidation from neutral Au0 to trivalent Au(iii) under certain oxidative environments provided by mild oxidizing reagent N-bromosuccinimide or amino acids. A new biolithography technique for gold patterning is further developed. © 2012 The Royal Society of Chemistry.

Zhang G.Q.,Tianjin Medical University
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2012

To reveal the iodine status of pregnant women and its impact on thyroid function of neonates in high iodine area. A total of 210 pregnant women were chosen from a hospital in Haixing county, Hebei province. Pregnant women's random urinary and neonates' cord blood were collected. The urinary iodine concentration (UIC) was examined by arsenic-cerium catalytic spectrophotometry. The levels of free triiodothyronine (FT3), free thyroxine (FT4) and sensitive thyroid-stimulating hormone (sTSH) in serum were measured by chemiluminescence. The age of 210 pregnant women was (27.69 +/- 4.73) years old, whose urinary iodine median (inter-quartile range ) was 1240.70 (1292.68) microg/L. 84.3% (177/210) of the pregnant women had excessive iodine intake (UIC > or = 500 microg/L), 13.8% (29/210) had more than adequate iodine intake( UIC within 250 - 499 microg/L), 0.5% (1/210) had adequate iodine intake (UIC within 150 - 249 microg/L) and 1.4% (3/210) had insufficient iodine intake (UIC < 150 microg/L). The average serum level of FT3, FT4 in neonates were (2.93 +/- 0.59), (15.03 +/- 1.92) pmol/L, respectively. The median (inter-quartile range) of serum sTSH in neonates were 7.33 (5.59) mU/L 78.1% (164/210) of the neonates' serum TSH were beyond 5 mU/L. There were no correlation between pregnant women's urinary iodine level and neonates' serum FT3 and sTSH level (P > 0.05), but there was a positive correlation between pregnant women's urinary iodine level and neonates' serum FT4 level (P < 0.01). Serum FT4 level of the neonates with whose mothers had insufficient iodine intake ((12.99 +/- 1.10) pmol/L) were statistically lower than those with their mothers had excessive iodine intake (15.16 +/- 1.83) pmol/L) (P < 0.05). Most of the pregnant women in high iodine area were excessive for iodine nutrition, but still a few pregnant women had insufficient iodine nutrition. The level of neonates' serum sTSH were relatively high and monitoring of risk of hypothyroidism and subclinical hypothyroidism should be strengthened.

Liu T.-B.,Rutgers University | Kim J.-C.,University of Kansas Medical Center | Wang Y.,Rutgers University | Wang Y.,Tianjin Medical University | And 5 more authors.
PLoS Pathogens | Year: 2013

Cryptococcus neoformans is the most common cause of fungal meningitis, with high mortality and morbidity. The reason for the frequent occurrence of Cryptococcus infection in the central nervous system (CNS) is poorly understood. The facts that human and animal brains contain abundant inositol and that Cryptococcus has a sophisticated system for the acquisition of inositol from the environment suggests that host inositol utilization may contribute to the development of cryptococcal meningitis. In this study, we found that inositol plays an important role in Cryptococcus traversal across the blood-brain barrier (BBB) both in an in vitro human BBB model and in in vivo animal models. The capacity of inositol to stimulate BBB crossing was dependent upon fungal inositol transporters, indicated by a 70% reduction in transmigration efficiency in mutant strains lacking two major inositol transporters, Itr1a and Itr3c. Upregulation of genes involved in the inositol catabolic pathway was evident in a microarray analysis following inositol treatment. In addition, inositol increased the production of hyaluronic acid in Cryptococcus cells, which is a ligand known to binding host CD44 receptor for their invasion. These studies suggest an inositol-dependent Cryptococcus traversal of the BBB, and support our hypothesis that utilization of host-derived inositol by Cryptococcus contributes to CNS infection. © 2013 Liu et al.

Ma X.M.,Tianjin Medical University
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2013

To compare the difference of receptor expression between primary and locally recurrent breast tumor tissues, and analyze their impact on survival of the patients. The expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) of primary and locally recurrent breast tumor tissues of 70 breast cancer patients were analyzed by immunohistochemistry or fluorescence in situ hybridization. The impact of the differences on overall survival (OS) and post-recurrence survival (PRS) of the patients was analyzed. The effective discrepancy rates between primary and locally recurrent breast cancer tissues were 26.1% (18/69) for ER, 50.0% (34/68) for PR, and 10.3%(4/39) for HER-2 expressions. In the 60 cases who had complete follow-up data, 23 patients (38.3%) died and the median overall survival was 107 months (11-288 months). The 3-, 5- and 10-year overall survival rates were 84.3%, 71.6% and 45.7%, respectively. Kaplan-Meier survival analysis showed that the changes of ER expression had significant impact on the OS (P = 0.001) and PRS (P < 0.001), but PR had no significant effect on OS (P = 0.416) and PRS (P = 0.056). However, the OS and PRS for patients with PR+ locally recurrent tumors were better than that of PR- patients regardless of the primary tumor PR status. The expression of HER-2 had no significant effect on the OS (P = 0.840) and PRS (P = 0.544) of the patients. An expression discrepancy of ER, PR and HER-2 exists between primary and locally recurrent breast cancer tissues, it significantly affects the survival of the patients. Re-evaluation of the expressions of ER, PR and HER-2 receptor in locally recurrent breast tumor tissue is beneficial for their therapy and prognosis.

To assess the changes about numbers and immune functions of splenic DC (dendritic cell) after a combined therapy of cryoablation and GM-CSF (granulocyte macrophage-colony stimulating factor) for prostate cancer. Murine model of prostate cancer was established. And the tumor-bearing mice were divided into 4 groups: control group (Group A), GM-CSF treatment (Group B), cryoablation treatment (Group C) and a combined therapy of cryoablation and GM-CSF (Group D). Spleens were sampled before and 7, 14, 21 days after treatment. Immunohistochemistry of DC was performed. And splenic lymphocytes were isolated and their activated percents analyzed by flow cytometry. The tumor-specific cytolytic activity of cytotoxic T lymphocyte (CTL) was measured by LDH (lactate dehydrogenase) assay. And the lung metastasis rates were calculated. At Day 7 post-treatment, the number of DC per high-power field was 26.4 ± 1.1, 36.6 ± 2.1, 25.8 ± 1.3 and 58.2 ± 1.9 (P < 0.05); the activated percent of DC 13.60% ± 1.67%, 9.50% ± 0.21%, 14.40% ± 1.14% and 32.80% ± 2.39% (P < 0.05); cytolytic activity of CTL against prostate cancer cells 7.76% ± 0.11%, 8.10% ± 0.92%, 9.38% ± 0.45% and 41.68% ± 0.82% in Groups A, B and C respectively (P < 0.05). At Day 21 post-treatment, the rate of lung metastasis was 5/5, 4/5, 4/5 and 1/5 respectively. A combined therapy of cryoablation and GM-CSF may increase the number and activated percent of DC in spleen, enhance the tumor-specific immune responses and decrease lung metastasis rate.

Chang B.C.,Tianjin Medical University
Zhonghua nei ke za zhi [Chinese journal of internal medicine] | Year: 2011

To evaluate the inhibitory effect of statins on glucose-stimulated insulin secretion (GSIS) of pancreatic islet in rat and to explore its mechanisms. According to the average volume, freshly isolated or 24-hour cultured pancreatic islets were randomly divided into control group (incubated with Kreb-Ringer bicarbonate buffer), the atorvastatin group (incubated with 100 μmol/L atorvastatin), the fluvastatin group (incubated with 100 μmol/L fluvastatin) and the pravastatin group (incubated with 100 μmol/L pravastatin). Stimulated by 2.8, 5.5, 11.1, 16.7 mmol/L and 25.0 mmol/L glucose respectively, the effect of 100 μmol/L statins on ATP content and GSIS was compared in the four groups. GSIS was performed by the 37°C bath incubation method and ATP content was measured by chemiluminescence method. Incubated with 100 μmol/L atorvastatin for 30 minutes, in the presence of 16.7 mmol/L glucose, the ATP content [(9.54 ± 1.64) pmol/islet vs (12.33 ± 1.89) pmol/islet] and GSIS (1.60 ± 0.21 vs 2.39 ± 0.30) were significantly reduced in comparison with the control group (P < 0.05). Cultured with 100 μmol/L fluvastatin for 24 hours, the ATP content [(10.24 ± 2.01) pmol/islet vs (12.31 ± 2.16) pmol/islet] and GSIS (3.12 ± 0.32 vs 4.17 ± 0.37) were all significantly decreased at the higher glucose concentration of 16.7 mmol/L (P < 0.05). Atorvastatin and fluvastatin may inhibit GSIS by decreasing ATP content in pancreatic islet and the inhibitory effect is related to the strength of its lipophilicity.

He X.,Tianjin Medical University
Orthopaedic surgery | Year: 2014

An operative approach to the inferior pubic ramus that was utilized in four patients with various bone tumors in the inferior pubic ramus is described here. These patients were successfully managed though a femoribus internus (inner thigh)-perineal approach. Data concerning preoperative and postoperative symptoms, surgical procedures, and outcomes are presented. There was no recurrence in the four cases and the pain associated with an initial pelvic floor had completely resolved except one case. The slight limitation in range of motion of the left hip joint and pain were performed in the same case postoperatively. The Musculoskeletal Tumor Society scores were 28, 15, 25, and 18 at the final follow-up. A typical case is described in full and our experience concerning surgical indications, and intraoperative issues in tumor patients discussed. The purpose of this paper is to recommend that the femoribus internus-perineal approach be used to resect the inferior pubic ramus, whether affected by osteomyelitis, bone tumor, or tuberculosis, but especially in patients with tumors. © 2014 Chinese Orthopaedic Association and Wiley Publishing Asia Pty Ltd.

Li Y.,Tianjin Medical University
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2013