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Tian Y.,Shenyang University | Xu Y.,Shenyang University | Xue T.,Shenyang University | Chen L.,Shenyang University | And 7 more authors.
Cell Death and Disease | Year: 2017

Our previous studies have confirmed the therapeutic effects of mesenchymal stem cell (MSC) monolayer sheet transplantation on allograft repair. A limiting factor in their application is the loss of MSC multi-potency as a result of high density sheet culture-induced senescence. In the study reported in this article, we tested whether Notch activation could be used to prevent or delay sheet culture-induced cell aging. Our results showed that, during in vitro long-term (5-day) cell sheet culture, MSCs progressively lose their progenitor characteristics. In contrast, Notch activation by Jagged1 in MSC sheet culture showed reduced cellular senescence and cell cycle arrest compared with control MSCs without Notch activation. Importantly, knockdown of Notch target gene Hes1 totally blocked the inhibition effect of Jagged1 on cellular senescence. Finally, the in vivo allograft transplantation data showed a significant enhanced callus formation and biomechanical properties in Notch activation cultured long-term sheet groups when compared with long-term cultured sheet without Notch activation. Our results suggest that Notch activation by Jagged1 could be used to overcome the stem cell aging caused by high density sheet culture, thereby increasing the therapeutic potential of MSC sheets for tissue regeneration. © The Author(s) 2017.


Guo H.,Longhua Hospital | Liu J.X.,Longhua Hospital | Xu L.,Longhua Hospital | Madebo T.,University of Stavanger | And 2 more authors.
Integrative Cancer Therapies | Year: 2011

Background: Targeted therapy (TT), chemotherapy, and traditional Chinese medicine herbal treatment (TCM) can improve the prognosis of advanced pulmonary adenocarcinoma patients. Their independent prognostic value is unknown. Objective: To study whether TCM improves survival in stage IV pulmonary adenocarcinoma patients with platinum-based chemotherapy (PBT), or combined PBT and second-line TT. Methods: Retrospective analysis of 133 fully ambulant clinical outpatients treated with PBT alone or PBT with/without second-line TT, with/without TCM. Univariate (Kaplan-Meier) and multivariable (Cox model) survival analysis were performed, using disease-specific mortality as an endpoint. Results: Gender (P =.002), TT (P <.0001), and TCM (P <.0001) had univariate prognostic value but not age, radiotherapy, or TCM syndrome differentiation (P >.10). TCM herbal treatment (P <.0001) and TT (P =.03) had multivariable independent prognostic value. TCM-treated patients (n = 103, PBT+TT+TCM+ = 62; PBT+TT-TCM+ =41) had 88% 1-year overall survival rate with median survival time (MST) of 27 months, contrasting 27% 1-year overall survival and MST of 5.0 months for non-TCM-treated (n = 30) patients. Patients with chemotherapy/TT/TCM (PBT+TT+TCM+, n = 62), TCM without TT (PBT+TT-TCM+, n = 41), or chemotherapy only (PBT+TT-TCM-, n = 30), had 1-year survival rates of 94%, 78%, and 27% respectively; for these 3 groups, respectively, MST was not reached (MST of 30.9 months), 22.6, and 5.0 months (P <.0001). Conclusions: TCM herbal treatment may improve survival of stage IV pulmonary adenocarcinoma patients treated with chemotherapy without or with second-line TT. This warrants formal phase 1 and 2 trials and ultimately properly designed prospective clinical validation trials with adequate methodology developed for data collection. © The Author(s) 2011.


PubMed | The PLA 452nd Hospital, Changzheng Hospital and Longhua Hospital
Type: Journal Article | Journal: The Annals of otology, rhinology, and laryngology | Year: 2015

Some studies have suggested that semicircular canal occlusion is effective and safe for treating intractable posterior semicircular benign paroxysmal positional vertigo (PSC-BPPV), and adverse effects of canal occlusions for intractable horizontal semicircular BPPV (HSC-BPPV) were rarely reported. The aim of this study was to retrospectively discuss the efficacy of semicircular canal occlusion for intractable HSC-BPPV with at least 2 years of follow-up.From 2000 to 2011, 3 female patients (average age=606.9 years), with a diagnosis of HSC-BPPV refractory to head-shake and barbecue roll maneuver, underwent semicircular canal occlusion treatment in our hospital. The supine roll test was performed to diagnose HSC-BPPV and evaluate the treatment efficacy.All patients with intractable HSC-BPPV had complete resolution of their positional vertigo after semicircular canal occlusion with a negative supine roll test. All patients reported transient postoperative disequilibrium, nausea, and vomiting, which resolved within 2 weeks. In addition, 1 patient (33.3%) had transient tinnitus, which resolved after 4 months. There were no other significant long-term complications.Semicircular canal occlusion appears to be a safe and well-tolerated treatment modality for intractable HSC-BPPV. However, further studies with large sample sizes are needed to confirm our conclusion.


PubMed | Guangzhou Women and Childrens Medical Center, Guangzhou University, University of Pisa and Longhua Hospital
Type: Journal Article | Journal: Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology | Year: 2016

2-Methoxyestradiol (2-ME) reduces atherosclerotic lesion formation. However, the underlying mechanisms remain largely unknown. In this work, we investigated the effect of 2-ME on monocyte adhesion to vascular endothelial cells. Lipopolysaccharides (LPS) greatly increased the attachment of monocyte onto cultured human umbilical vascular endothelial cells (HUVECs), which was inhibited by 2-ME in a dose- and time-dependent manner, or by the vascular cell adhesion protein-1 (VCAM-1) neutralizing antibody, suggesting that a functional releationship between 2-ME and VCAM-1 may exist. In accordance with this, treatment with 2-ME (10(-)(7)-10(-)(5) M) for 6-48h downregulated VCAM-1 protein expression. Meanwhile, the nuclear factor B (NF-B) p65 subunit activity and its nuclear translocation was inhibited by 2-ME in HUVECs. The PI3K inhibitor wortmannin or the specific Akt siRNA both inhibited the effects of 2-ME, suggesting that 2-ME inhibited p65 activity via PI3K/Akt signaling. In conclusion, 2-ME inhibits VCAM-1 expression and thus prevents monocyte adhesion to vascular endothelial cells via regulation of PI3K/Akt and NF-B signaling. These findings will be helpful for better understanding the mechanisms through which 2-ME improves endothelial function.


PubMed | Fudan University, Aurora University and Longhua Hospital
Type: Journal Article | Journal: Current oncology (Toronto, Ont.) | Year: 2016

Traditional Chinese Medicine (tcm) is used in China as part of the treatment for non-small-cell lung cancer (nsclc) and often includes prescription of herbal therapy based on syndrome differentiation. Studies of various Astragalus-based Chinese medicines combined with platinum-based chemotherapy in the treatment of lung cancer are popular in East Asia, particularly in China. The aim of the present study was to perform a systematic review and meta-analysis comparing platinum-based chemotherapy alone with platinum-based chemotherapy plus Astragalus-based Chinese botanicals, with and without prescription based on syndrome differentiation, as first-line treatment for advanced nsclc.We searched the Chinese Biomedical Literature database, the China National Knowledge Internet, the VIP Chinese Science and Technology Periodicals Database, PubMed, embase, the Cochrane databases, and abstracts presented at meetings of the American Society of Clinical Oncology, the World Conference on Lung Cancer, the European Society for Medical Oncology, and the Chinese Society of Clinical Oncology for all eligible studies. Endpoints were overall survival; 1-year, 2-year, and 3-year survival rates; performance status; overall response rate; and grade 3 or 4 adverse events. Subgroup analyses based on herbal formulae individualized using syndrome differentiation or on oral or injection patent medicines were performed using the Stata software application (version 11.0: StataCorp LP, College Station, TX, U.S.A.) and a fixed-effects or random-effects model in case of heterogeneity. Results are expressed as a hazard ratio (hr) or relative risk (rr), with corresponding 95% confidence intervals (cis).Seventeen randomized studies with scores on the Jadad quality scale of 2 or more, representing 1552 patients, met the inclusion criteria. Compared with platinum-based chemotherapy alone, the addition of Astragalus-based tcm to chemotherapy was associated with significantly increased overall survival (hr: 0.61; 95% ci: 0.42 to 0.89; p = 0.011); 1-year (rr: 0.73; 95% ci: 0.65 to 0.82; p < 0.001), 2-year (rr: 0.3344; 95% ci: 0.237 to 0.4773; p < 0.001), and 3-year survival rates (rr: 0.30; 95% ci: 0.17 to 0.53; p < 0.001); performance status (rr: 0.43; 95% ci: 0.34 to 0.55; p < 0.001); and tumour overall response rate (rr: 0.7982; 95% ci: 0.715 to 0.89; p < 0.001). Subgroup analyses indicated that Astragalus herbal formulae given based on syndrome differentiation were more effective than Astragalus-based oral and injection patent medicines. Side effects-including anemia, neutropenia, thrombocytopenia, fatigue, poor appetite, nausea, and vomiting-were significantly more frequent with platinum-based chemotherapy alone than when platinum-based chemotherapy was combined with Astragalus-based tcm.Astragalus-based Chinese botanical therapy, especially when based on syndrome differentiation, is associated with increased efficacy of platinum-based chemotherapy and decreased platinum-derived toxicities for patients with advanced nsclc.


Zhao Q.-H.,Longhua Hospital | Zhou X.,Longhua Hospital | Xie R.-F.,Longhua Hospital | Li Z.-C.,Nanhui Central Hospital
Journal of Liquid Chromatography and Related Technologies | Year: 2011

Three weighing methodological approaches, including Analytic Hierarchy Process (AHP), Criteria Importance Through Intercriteria Correlation (CRITIC), and synthetic method (AHP combined with CRITIC), were proposed to handle the relative importance of different constituents in the HPLC fingerprints of cortex fraxini. The consistency and rationale of the three methods have been analyzed and compared. Results showed satisfying consistency in all three methods; the synthetic method reflected both the analyst's subjective judgments and the objective data itself and was, therefore, more representative than either of the other two methods alone. We conclude that the synthetic method is a reliable and appropriate method to evaluate the HPLC fingerprint of Traditional Chinese Medicine (TCM). Copyright © Taylor & Francis Group, LLC.


Zhu Q.,Changzheng Hospital | Liu C.H.A.N.G.,Longhua Hospital | Lin C.,PLA 452nd Hospital | Chen X.I.A.N.,PLA 452nd Hospital | And 3 more authors.
Annals of Otology, Rhinology and Laryngology | Year: 2015

Background: Some studies have suggested that semicircular canal occlusion is effective and safe for treating intractable posterior semicircular benign paroxysmal positional vertigo (PSC-BPPV), and adverse effects of canal occlusions for intractable horizontal semicircular BPPV (HSC-BPPV) were rarely reported. The aim of this study was to retrospectively discuss the efficacy of semicircular canal occlusion for intractable HSC-BPPV with at least 2 years of follow-up. Methods: From 2000 to 2011, 3 female patients (average age = 60 ± 6.9 years), with a diagnosis of HSC-BPPV refractory to head-shake and barbecue roll maneuver, underwent semicircular canal occlusion treatment in our hospital. The supine roll test was performed to diagnose HSC-BPPV and evaluate the treatment efficacy. Results: All patients with intractable HSC-BPPV had complete resolution of their positional vertigo after semicircular canal occlusion with a negative supine roll test. All patients reported transient postoperative disequilibrium, nausea, and vomiting, which resolved within 2 weeks. In addition, 1 patient (33.3%) had transient tinnitus, which resolved after 4 months. There were no other significant long-term complications. Conclusion: Semicircular canal occlusion appears to be a safe and well-tolerated treatment modality for intractable HSC-BPPV. However, further studies with large sample sizes are needed to confirm our conclusion. © The Author(s) 2014.


Ye Y.,Longhua Hospital | Han X.,Longhua Hospital | Guo B.,Longhua Hospital | Sun Z.,Longhua Hospital | Liu S.,Longhua Hospital
Environmental Toxicology and Pharmacology | Year: 2013

In this study, two invasive mammary carcinoma cells (MDA-MB-231 and 4T1) were utilized to evaluate the inhibitory activities of platycodin D, osthole, and the two in combination. The anti-proliferative effect was tested using the MTT and BrdU assay, and the combination of 15. μM osthole and 75. μM platycodin D was used for subsequent analyses. The anti-invasive effect was evaluated by the transwell assay. The results showed that the combination treatment reduced both cell proliferation and invasion. Western blot and real-time PCR revealed that the platycodin D-osthole combination significantly decreased TβRII, Smad2, Smad3 and Smad4 gene or protein expressions, as well as effectively blocked TGF-β-induced phosphorylation of Smad2 and Smad3. Thus, this study demonstrates that the anti-cancer effects of the platycodin D-osthole combination in breast cancer cells involve proliferation inhibition and invasion blockade, both of which may be mediated by perturbations in the TGF-β/Smads pathway. © 2013 Elsevier B.V.


Ye Y.,Longhua Hospital | Liu S.,Longhua Hospital | Wu C.,Longhua Hospital | Sun Z.,Longhua Hospital
Journal of Molecular Histology | Year: 2015

The formation of tumor-promoting premetastatic microenvironment plays a pivotal role on metastatic progression. Understanding how the primary tumor can promote the formation of premetastatic microenvironment in the lung will aid discovery of a final cure for metastatic breast cancer. The murine 4T1 mammary carcinoma cells were injected into the mammary fat pads of the BALB/c mice. Days 0–14 were considered the premetastatic phase. Lung tissues were examined using hematoxylin-eosin staining and transmission electron microscopy. After intravenous injection of TGFβ1 pretreated 4T1 cells, the relative pulmonary vascular permeability was quantified, the extravasation, survival, and proliferation of tumor cells in premetastatic lungs were evaluated, and the levels of S100A8, S100A9, VEGF, and Angpt2 were detected in tumor-bearing mice. The results showed that during the premetastatic phase, an inflammatory response and inflammation-induced vascular hyperpermeability were established, leading to an abnormal pulmonary microenvironment, which facilitated extravasation of circulating tumor cells, and subsequent survival and proliferation of metastatic tumor cells in a TGFβ-dependent manner. Moreover, the expressions of S100A8, S100A9, VEGF, and Angpt2 were increased, and an induction of these genes by TGFβ was further observed in premetastatic lungs. Thus, this study demonstrated that TGFβ promoted the creation of premetastatic microenvironment by modulating certain crucial inflammatory cytokines and growth factors, and finally enhanced the ability of circulating cells to seed the lung. © 2015, Springer Science+Business Media Dordrecht.


PubMed | Longhua Hospital
Type: Journal Article | Journal: Environmental toxicology and pharmacology | Year: 2013

In this study, two invasive mammary carcinoma cells (MDA-MB-231 and 4T1) were utilized to evaluate the inhibitory activities of platycodin D, osthole, and the two in combination. The anti-proliferative effect was tested using the MTT and BrdU assay, and the combination of 15M osthole and 75M platycodin D was used for subsequent analyses. The anti-invasive effect was evaluated by the transwell assay. The results showed that the combination treatment reduced both cell proliferation and invasion. Western blot and real-time PCR revealed that the platycodin D-osthole combination significantly decreased TRII, Smad2, Smad3 and Smad4 gene or protein expressions, as well as effectively blocked TGF--induced phosphorylation of Smad2 and Smad3. Thus, this study demonstrates that the anti-cancer effects of the platycodin D-osthole combination in breast cancer cells involve proliferation inhibition and invasion blockade, both of which may be mediated by perturbations in the TGF-/Smads pathway.

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