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Yang D.,Nanjing Southeast University | Lu X.,Nanjing Southeast University | Hong Y.,Nanjing Drum Tower Hospital | Xi T.,Peking University
Biomaterials | Year: 2014

The aim of this study is to systematically investigate the molecular mechanism of different effects of nickel titanium (NiTi) alloy surface and titanium nitride (TiN) coating on endothelial cell function. Release of nickel (Ni) ion from bare and TiN-coated NiTi alloys and proliferation of endothelial cells on the two materials were evaluated, and then influence of the two materials on cellular protein expression profiles was investigated by proteomic technology. Subsequently, proteomic data were analyzed with bioinformatics analyses and further validated using a series of biological experiments. Results showed that although the two materials did not affect cell proliferation, the Ni ions released from bare NiTi alloy generated inhibition on pathways associated with actin cytoskeleton, focal adhesion, energy metabolism, inflammation, and amino acid metabolism. In comparison, TiN coating not only effectively prevented release of Ni ions from NiTi alloy, but also promoted actin cytoskeleton and focal adhesion formation, increased energy metabolism, enhanced regulation of inflammation, and promoted amino acid metabolism. Furthermore, the two processes, "the initial mediation of adsorbed serum protein layer to endothelial cell adhesion and growth on the two materials" from our previous study, and "the following action of the two materials on cellular protein expression profile", were linked up and comprehensively analyzed. It was found that in stage of cell adhesion (within 4h), release of Ni ions from bare NiTi alloy was very low, and the activation of adsorbed proteins to cell adhesion and growth related biological pathways (such as regulation of actin cytoskeleton, and focal adhesion pathways) was almost as same as TiN-coated NiTi alloy. This indicated that the released Ni ions did not affect the mediation of adsorbed proteins to endothelial cell adhesion. However, in stage of cell growth and proliferation, the release of Ni ions from bare NiTi alloy increased with time and reached a higher level, which inhibited endothelial cell function at molecular level, whereas TiN coating improved endothelial cell function. © 2014 Elsevier Ltd.


Ji L.,Peking University | Lu J.,Chinese PLA General Hospital | Weng J.,Sun Yat Sen University | Jia W.,Shanghai 6th Hospital | And 4 more authors.
Journal of Diabetes | Year: 2015

Background: The aim of the present study was to investigate the current status of oral anti-diabetic drug (OAD) therapy in patients with type 2 diabetes and influencing factors in a real-world setting in China. Methods: A total of 9872 outpatients with type 2 diabetes, who had received OADs (monotherapy or combination therapy) for at least 3 months were recruited in this study. Current antidiabetic treatment regimen and related clinical data were collected from medical records and analyzed. Results: The most common OADs in use were insulin secretagogues (70.2%) such as sulfonylureas (SUs; 42.7%) or glinides (27.5%), followed by metformin (53.7%), α-glucosidase inhibitors (35.9%), thiazolidinediones (17.2%), and dipeptidyl peptidase-4 (DPP-4) inhibitors (0.8%). Dual-drug combination therapy was more common (45.4%) than monotherapy (35.8%) and combination therapy with at least three drugs (17.0%). Patients on SU or glinide monotherapy were more likely to alter their treatment frequently (odds ratio [OR], 1.7; 95% CI, 1.38-2.08; P<0.001). Conclusions: The status of OAD use in China is varied with a majority of the patients altering their treatment regimen citing poor effectiveness. These observations from a real-world setting may serve as guidance for improving diabetes management in China. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.


Yang D.,Nanjing Southeast University | Lu X.,Nanjing Southeast University | Hong Y.,Nanjing Drum Tower Hospital | Xi T.,Peking University
Biomaterials | Year: 2013

To explore molecular mechanism of mediation of adsorbed proteins to cell adhesion and growth on biomaterials, this study examined endothelial cell adhesion, morphology and viability on bare and titanium nitride (TiN) coated nickel titanium (NiTi) alloys and chitosan film firstly, and then identified the type and amount of serum proteins adsorbed on the three surfaces by proteomic technology. Subsequently, the mediation role of the identified proteins to cell adhesion and growth was investigated with bioinformatics analyses, and further confirmed by a series of cellular and molecular biological experiments. Results showed that the type and amount of adsorbed serum proteins associated with cell adhesion and growth was obviously higher on the alloys than on the chitosan film, and these proteins mediated endothelial cell adhesion and growth on the alloys via four ways. First, proteins such as adiponectin in the adsorbed protein layer bound with cell surface receptors to generate signal transduction, which activated cell surface integrins through increasing intracellular calcium level. Another way, thrombospondin 1 in the adsorbed protein layer promoted TGF-β signaling pathway activation and enhanced integrins expression. The third, RGD sequence containing proteins such as fibronectin 1, vitronectin and thrombospondin 1 in the adsorbed protein layer bound with activated integrins to activate focal adhesion pathway, increased focal adhesion formation and actin cytoskeleton organization and mediated cell adhesion and spreading. In addition, the activated focal adhesion pathway promoted the expression of cell growth related genes and resulted in cell proliferation. The fourth route, coagulation factor II (F2) and fibronectin 1 in the adsorbed protein layer bound with cell surface F2 receptor and integrin, activated regulation of actin cytoskeleton pathway and regulated actin cytoskeleton organization. © 2013 Elsevier Ltd.


Zhao X.,Harvard University | Zhao X.,Nanjing Drum Tower Hospital | Boenisch O.,Harvard University | Yeung M.,Harvard University | And 7 more authors.
American Journal of Transplantation | Year: 2012

The proinflammatory cytokine IL-6 plays an important role in controlling T-cell differentiation, especially the development of Th17 and regulatory T cells. To determine the function of IL-6 in regulating allograft rejection and tolerance, BALB/c cardiac grafts were transplanted into wild-type or IL-6-deficient C57BL/6 mice. We observed that production of IL-6 and IFN-γ was upregulated during allograft rejection in untreated wild-type mice. In IL-6-deficient mice, IFN-γ production was greater than that observed in wild-type controls, suggesting that IL-6 production affects Th1/Th2 balance during allograft rejection. CD28-B7 blockade by CTLA4-Ig inhibited IFN-γ production in C57BL/6 recipients, but had no effect on the production of IL-6. Although wild-type C57BL/6 recipients treated with CTLA4-Ig rejected fully MHC-mismatched BALB/c heart transplants, treatment of IL-6-deficient mice with CTLA4-Ig resulted in graft acceptance. Allograft acceptance appeared to result from the combined effect of costimulatory molecule blockade and IL-6-deficiency, which limited the differentiation of effector cells and promoted the migration of regulatory T cells into the grafts. These data suggest that the blockade of IL-6, or its signaling pathway, when combined with strategies that inhibit Th1 responses, has a synergistic effect on the promotion of allograft acceptance. Thus, targeting the effects of IL-6 production may represent an important part of costimulation blockade-based strategies to promote allograft acceptance and tolerance. © Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.


Huang Q.,Nanjing Drum Tower Hospital | Huang Q.,Harvard University | Fang D.C.,Southwest University | Yu C.G.,Nanjing Drum Tower Hospital | And 2 more authors.
Journal of Digestive Diseases | Year: 2011

Barrett's esophagus (BE)-related esophageal adenocarcinoma (EAC) has shown the fastest rise in incidence in Western countries; however, research data on BE-related diseases from China are inconclusive. We aimed to review and analyze the published results on these diseases in China. We searched PubMed and Chinese medical literature for key words: BE, EAC, Chinese and China. Relevant research papers along with the study results from our own groups were reviewed and analyzed. Using standardized criteria, columnar-lined esophagus (CLE) was found in as many as 29% of resection specimens in Chinese patients with proximal gastric cancer. However, BE with intestinal metaplasia was rare, ranging from 0.06% in the general population to <2% in referral patients. Risk factors included advancing age, hiatal hernia and probably gastroesophageal reflux disease and tobacco or alcohol abuse, but not male gender or obesity. At endoscopy, most CLE/BE were <2cm in length, and appeared tongue-like and island-like. The long-segment BE was rare, especially in women. Population-based studies conducted in Taiwan and Hong Kong SAR, China showed that EAC was not only rare but also stable or had decreased in incidence over the past decade. By histopathology, EAC accounted for only 1% of all distal esophageal cancers and almost all gastroesophageal junction (GEJ) cancers were centered in the proximal stomach. BE-related diseases, except for CLE, are rare in China. The clinical significance and malignant potential of CLE in the Chinese population remain elusive. Further investigation on these diseases is in progress. © 2011 The Authors. Journal of Digestive Diseases © 2011 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.


Chen S.,Wuhan University | Shi H.,Tongji University | Zou X.,Nanjing Drum Tower Hospital | Luo H.,Wuhan University
Pancreas | Year: 2010

Objectives: The role of prophylactic ulinastatin in the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is debated. A meta-analysis of all published randomized clinical trials was performed to evaluate the efficacy of ulinastatin on post-ERCP pancreatitis. Methods: Searches were conducted in multiple databases composed of PubMed, EMBASE, the Cochrane Library, the Science Citation Index Expanded, and the China National Knowledge Infrastructure series full-text database. Primary outcome was post-ERCP pancreatitis, with or without hyperamylasemia. Results: Seven randomized clinical trials fulfilling the inclusion criteria were selected for meta-analysis, 5 comparing ulinastatin with placebo and 2 for ulinastatin versus gabexate. The incidence of post-ERCP pancreatitis was reduced by ulinastatin (odds ratio, 0.53; 95% confidence interval, 0.31-0.89; P = 0.02; test for heterogeneity: I2 = 0%; P = 0.51), so was the event of hyperamylasemia (odds ratio, 0.42; 95% confidence interval, 0.30-0.59; P < 0.00001; test for heterogeneity: I2 = 13%; P = 0.33). Subsequent sensitivity and subgroup analyses produced conflicting results. Conclusions: Ulinastatin shows to be of value on preventing post-ERCP pancreatitis and hyperamylasemia for patients in average risk, when given intravenously at a dose of not less than 150,000 U, just before ERCP. More high-quality trials are needed for further confirmation. © 2010 by Lippincott Williams & Wilkins.


Huang Q.,Nanjing Drum Tower Hospital | Huang Q.,Harvard University
World Journal of Gastroenterology | Year: 2012

Carcinoma of the gastroesophageal junction (GEJ) is defined as carcinoma that crosses the GEJ line, irrespective of where the tumor epicenter is located. This group of cancer is rare but controversial. Based on study results from the majority of epidemiologic and clinicopathologic investigations carried out in Western countries, this cancer is believed to arise from Barrett's esophagus (BE) and includes both distal esophageal and proximal gastric carcinomas because of similar characteristics in epidemiology, clinicopathology, and molecular pathobiology in relation to BE. As such, the most recent American Joint Committee on Cancer staging manual requires staging all GEJ carcinomas with the rule for esophageal adenocarcinoma (EA). This mandate has been challenged recently by the data from several studies carried out mainly in Chinese patients. The emerging evidence derived from those studies suggests: (1) both BE and EA are uncommon in the Chinese population; (2) almost all GEJ cancers in Chinese arise in the proximal stomach and show the features of proximal gastric cancer, not those of EA; (3) application of the new cancer staging rule to GEJ cancer of Chinese patients cannot stratify patients' prognosis effectively; and (4) prognostic factors of GEJ cancer in Chinese are similar, but not identical, to those of EA. In conclusion, the recent evidence suggests that GEJ cancer in Chinese shows distinct clinicopathologic characteristics that are different from EA. Further investigations in molecular pathology may help illustrate the underlying pathogenesis mechanisms of this cancer in Chinese patients and better manage patients with this fatal disease. © 2012 Baishideng. All rights reserved.


Ling T.,Nanjing Drum Tower Hospital | Guo H.,Nanjing Drum Tower Hospital | Zou X.,Nanjing Drum Tower Hospital
Journal of Gastroenterology and Hepatology (Australia) | Year: 2014

Background and Aim: To investigate the effectiveness of peroral endoscopic myotomy (POEM) surgery in achalasia patients with failure of prior pneumatic dilation (PD). Methods: Twenty-one patients with a history of failed PD were prospectively recruited as the case group, and 30 patients with no history of prior treatment for achalasia were included as the control group. Outcome of POEM procedures was evaluated through esophageal manometry, timed barium esophagogram and short form 36 (SF-36) questionnaires, which were performed before surgery, at 5 days after surgery and at the last follow-up, respectively. Relief of patients' symptoms was considered as the primary outcome. Secondary outcomes included lower esophageal sphincter pressure, esophageal emptying, quality of life of the patient, and procedure-related complications. Results: The two groups were matched in terms of age, gender, body mass index, and results of preoperative examinations. For patients with failed PD, it was observed that Eckardt score, lower esophageal sphincter pressure, and height of the barium column were significantly decreased after POEM surgery. Besides, the mean physical component summary and mental component summary of patients at the final follow were significantly higher than those before surgery. Complications that occurred during the surgery included three cases of subcutaneous emphysema (14.3%) and one case of pneumothorax (4.8%). Patients with failed PD were found to have the significantly longer operation time than the control group. There was no significant difference between the two groups in terms of surgical outcome at the final follow-up. Conclusions: POEM is a promising therapeutic modality for achalasia patients who have failed to respond to PD therapy. Previous dilation procedures might have no obvious influence on the efficacy of POEM surgery. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.


Cao B.,Nanjing Drum Tower Hospital | Shi Q.,Nanjing Drum Tower Hospital | Wang W.,Nanjing Drum Tower Hospital
Journal of Thoracic Disease | Year: 2015

Background: High expression of Sirtuin type 1 (SIRT1) exists in some cancer cells. However, it is still unclear whether SIRT1 affects the sensitivity of esophageal cancer cells to cisplatin. This study was designed to explore the relationship between SIRT1 expression and resistance of esophageal squamous cell carcinoma (ESCC) cells to cisplatin and reveal the underlying mechanism. Methods: The tissue samples of 68 ESCC patients were collected from Nanjing Drum Tower Hospital, China. All the patients had undergone cisplatin based combination chemotherapy. The expression of SIRT1and Noxa in tissue samples were analyzed by quantitative real-time reverse PCR (qRT-PCR) and Western blot. Human ESCC cell line (ECa9706 cells) was cultured and a cisplatin-resistant subline (ECa9706-CisR cells) was established by continuous exposure to cisplatin at different concentrations. The expression of SIRT1 and Noxa in both cell lines was analyzed by qRT-PCR and Western blot. siRNA technology was utilized to down-regulate the SIRT1 expression in ECa9706-CisR cells. The influence of SIRT1 silence on sensitivity of ECa9706-CisR cells to cisplatin was confirmed using CCK-8 assay and flow cytometry. Furthermore, the level change of Noxa after SIRT1 silence in ECa9706-CisR cells was determined by qRT-PCR and Western blot. Result: SIRT1 and Noxa expression in chemo-resistant patients was significantly increased and decreased respectively, compared with chemo-sensitive patients. SIRT1 expression in ECa9706-CisR cells was significantly increased with a lower Noxa level, compared with normal ECa9706 cells. Cisplatin 5 μM could cause proliferation inhibition, G2/M phase arrest and apoptosis in ECa9706-CisR cells and these effects could be enhanced dramatically by SIRT1 silencing. Moreover, Noxa expression was increased after treated with SIRT1 siRNA. Conclusions: Over-expression of SIRT1 may cause resistance of ESCC cells to cisplatin through the mechanism involved with Noxa expression. © Journal of Thoracic Disease.


News Article | April 13, 2016
Site: phys.org

Nanozymes are novel nanomaterials with enzyme mimicking activities, which are superior to natural enzymes and even conventional artificial enzymes. They have attracted considerable attention because they offer the possibility of lowered cost, improved stability, and excellent recyclability. However, the specificity and catalytic activity of current nanozymes are still far lower than that of their natural counterparts, which in turn have limited their broad applications. To tackle this challenge, Professor Wei and his team from Nanjing University, Nanjing Drum Tower Hospital, and Emory University now report the design and development of integrated nanozymes by confining two cascade catalysts inside a nanostructured metal-organic framework. A major advantage of this integrated design is that the first enzymatic reaction occurs in nanoscale proximity to the second enzyme, so products of the first reaction can be used immediately as substrates for the second reaction, thus overcoming the problems of diffusion-limited kinetics and product instability. Specifically, a molecular catalyst (e.g., hemin) and a natural enzyme (e.g., glucose oxidase, GOx) have been simultaneously assembled inside a nanoscaled zeolitic imidazolate framework (ZIF-8), and the resulting GOx/hemin@ZIF-8 integrated nanozymes show numerous merits such as enhanced catalytic activity and improved thermal stability. Quantitative enzymatic studies indicate that their integrated nanozymes are able to provide greater than 600 percent enhancement in catalytic activity relative to a simple mixture of hemin@ZIF-8 and GOx@ZIF-8. Their strategy is general and has also been applied to other enzymes (e.g., lactate oxidase/hemin@ZIF-8) and multiple catalysts (e.g., invertase/GOx/hemin@ZIF-8). More excitingly, this dramatic improvement in catalytic activity has allowed them to construct an integrative detection platform by combining the nanozymes with microdialysis and microfluidic techniques. The platform has been successfully employed for the in vivo monitoring of neurochemicals such as striatum glucose in the brains of living rats following ischemia/reperfusion. Considering the vast numbers of combinations of nanozymes with other artificial enzymes and/or natural enzymes, their current strategy and platform might be extended for a wide range of targets associated with many critical diseases in other living animals and even human beings. Explore further: Structures made of polymer chains allow organic catalysts to work in water More information: Hanjun Cheng et al. Integrated nanozymes with nanoscale proximity for neurochemical monitoring in living brains , Analytical Chemistry (2016). DOI: 10.1021/acs.analchem.6b00975

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