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Tan Q.,Institute of Surgery Research | Zhang L.,Chongqing Medical University | Teng Y.,Chongqing Medical University | Zhang J.,Chongqing Medical University
Chemical and Pharmaceutical Bulletin

Pyridostigmine bromide (PTB) is a highly soluble and extremely bitter drug. Here, an economic complexation technology combined with direct tablet compression method has been developed to meet the requirements of a patient friendly dosage known as taste-masked dispersible tablets loaded PTB (TPDPTs): (1) TPDPTs should have optimal disintegration and good physical resistance (hardness); (2) a low-cost, simple but practical preparation method suitable for industrial production is preferred from a cost perspective. Physicochemical properties of the inclusion complex of PTB with beta-cyclodextrin were investigated by Fourier transformed infrared spectroscopy, differential scanning calorimetry and UV spectroscopy. An orthogonal design was chosen to properly formulate TPDPTs. All volunteers regarded acceptable bitterness of TPDPTs. The properties including disintegration time, weight variation, friability, hardness, dispersible uniformity and drug content of TPDPTs were evaluated. The dissolution profile of TPDPTs in distilled water exhibited a fast rate. Pharmacokinetic results demonstrated that TPDPTs and the commercial tablets were bioequivalent. © 2012 The Pharmaceutical Society of Japan. Source

Proton pump inhibitor (PPI) was the main prescription for gastric ulcer after endoscopic submucosal dissection (ESD). Some randomized controlled trials showed that a combination of rebamipide and PPI appears to be more efficient than PPI alone for the treatment of ESD-induced gastric ulcer. However, the sample sizes in these trials were limited and the conclusions were underpowered.This meta-analysis was conducted with 5 randomized controlled trials using the combination of rebamipide and PPI for healing ESD-induced ulcer compared with PPI monotherapy. Relevant studies were searched via MEDLINE, PubMed, Embase, and Cochrane Library databases by using terms such as "rebamipide," "proton pump inhibitor," "endoscopic submucosal dissection," "drug therapy," and "gastric ulcer or artificial ulcer."Five studies were included in this meta-analysis. The number of total patients was 626, with 317 patients in the combination group and 309 patients in the PPI alone group. The heterogeneity among these 5 studies was low (I = 22%, P = 0.28). All 5 studies considered scarring stage 1 rate as a primary endpoint, and the scarring stage 1 rate in combination group (115/317) was higher than that in PPI alone group (63/309) (odds ratio 2.61, 95% confidence interval [CI] 1.76-3.88). The mean difference of initial ulcer size between 2 groups was -4.46 (95% CI -266.61 to -257.69, P = 0.97), but it enlarged to 68.38 (95% CI 35.72-101.05, P < 0.00001) in the 4th week.This meta-analysis demonstrates that combination therapy is more efficient than PPI monotherapy in healing ESD-induced gastric ulcer. Source

Liu D.,Chongqing Medical University | Liu D.,Institute of Surgery Research | Zhou P.,Chongqing Medical University | Zhang L.,Chongqing Medical University | And 3 more authors.
Tumor Biology

The colony-forming ability of cervical cancer is affected by many factors. Oct4, an important transcription factor, is highly expressed in several tumors and promotes the colony-forming ability of cancer cells. Thus, it is considered a potential target for the treatment of cancer. However, we know little about the expression level of Oct4 and its epigenetic regulatory mechanism in cervical cancer cells. In this study, we are the first to observe that human papillomavirus (HPV)-positive cervical cancer cell lines (HeLa, Caski) have a stronger colony-forming ability than HPV-negative cervical cancer cell lines (C-33A). Moreover, the expression level of Oct4 in both HeLa and Caski cells was also higher than that in C-33A cells. We then confirmed that there was a negative correlation between the expression of Oct4 and DNMT3A in these three types of cervical cancer cells, whereas DNA methyltransferase 1 and 3B had no differences among the cell lines. However, after DNA methylation in both key regulatory regions of the Oct4 gene and the genomic levels were analyzed, we found that DNA methyltransferase 3A could neither regulate the expression of Oct4 nor affect the whole level of genomic DNA methylation. These results suggest three points: (1) Oct4 might be treated as a new target for the treatment of cervical cancer, (2) we could not inhibit the expression of Oct4 by DNA demethylation, and (3) HPV virus might initiate cervical carcinogenesis by upregulation of Oct4 expression. © 2011 International Society of Oncology and BioMarkers (ISOBM). Source

Chen K.-H.,Institute of Surgery Research | Zeng L.,Institute of Surgery Research | Gu W.,Institute of Surgery Research | Zhou J.,Chongqing Medical University | And 2 more authors.
British Journal of Surgery

Background: Toll-like receptor (TLR) 9 is the pattern recognition receptor for microbial DNA. Genetic variation within pattern recognition receptors for bacterial endotoxin and exotoxin has been shown to be associated with the risk of sepsis and organ dysfunction in critical illness. However, little is known about the clinical relevance of TLR9 gene polymorphisms in critical illness. Methods: A total of 557 patients with major blunt trauma were included in the study. Genetic variation data for the entire TLR9 gene were obtained from the HapMap Project. The genotypes of TLR9 gene polymorphisms were determined using a pyrosequencing method. Whole peripheral blood samples obtained immediately after admission were stimulated with bacterial DNA and production of tumour necrosis factor (TNF) α was then determined. Sepsis morbidity rate and multiple organ dysfunction (MOD) scores were assessed. Results: Of five single-nucleotide polymorphisms (SNPs) genotyped, four (rs187084, rs352139, rs352140 and rs352162) existed as common SNPs and were in strong linkage disequilibrium. Both rs187084 and rs352162 were significantly associated with TNF-α production by peripheral blood leucocytes in response to bacterial DNA stimulation and a higher sepsis morbidity rate in patients with major trauma. In addition, the rs352162 polymorphism was significantly associated with MOD scores, whereas rs187084 showed a trend to be associated with MOD score. Conclusion: TLR9 polymorphisms rs187084 and rs352162 might be used to provide relevant risk estimates for the development of sepsis and MOD in patients with major trauma. © 2011 British Journal of Surgery Society Ltd. Published by John Wiley and Sons Ltd. Source

Li Y.,Institute of Surgery Research | Liu L.,Biowave Center | Wang B.,Institute of Surgery Research | Wang J.,Institute of Surgery Research | Chen D.,Institute of Surgery Research
European Journal of Gastroenterology and Hepatology

OBJECTIVES: Hematocrit levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) and related to hypoxia and hyperlipidemia. AIM: This study was conducted to investigate the association between elevated hematocrit and liver histology in patients with NAFLD. PATIENTS AND METHODS: We examined 215 consecutive adults with biopsy-proven NAFLD (108 with steatosis alone, 107 with nonalcoholic steatohepatitis) and 110 controls. The stage of fibrosis was measured using a four-point scale. All underwent anthropometric and metabolic profiling. Hematocrit and related hematologic variables such as blood viscosity and red blood cell count were also measured. RESULTS: NAFLD morbidity was found to be positively correlated with hematocrit levels. After adjusting for age, smoking, diabetes, BMI, homeostasis model assessment of insulin resistance, triglycerides, and obstructive sleep apnea, patients with hematocrit levels in the highest quartile were seen to have had an odds ratio of 3.05 (95% confidence interval 2.12-4.36, P=0.015) for NAFLD in males. Hematocrit levels increased significantly (P<0.001) in steatosis (42.4±4.6%) compared with control groups (38.2±4.2%), and in nonalcoholic steatohepatitis (45.1±5.2%) compared with steatosis patients. On multivariate analysis, hematocrit levels were found to be strongly and independently associated with fibrosis (β=0.205, P=0.030). Moreover, hematocrit levels increased with the severity of hepatic fibrosis (P<0.05). CONCLUSION: Our results indicate that hematocrit levels are significantly increased and independently associated with fibrosis in NAFLD patients. Therefore, hematocrit levels may have potential interest as a clinical marker of NAFLD severity. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

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