BACKGROUND: The occurrence and development of lung cancer are closely linked to epigenetic modification. Abnormal DNA methylation in the CpG island region of genes has been found in many cancers. Protein kinase C delta binding protein (PRKCDBP) is a potential tumor suppressor and its epigenetic changes are found in many human malignancies. This study investigated the possibility of PRKCDBP methylation as a potential biomarker for non-small cell lung cancer (NSCLC). METHODS: We measured the methylation levels of PRKCDBP in the three groups of NSCLC tissues. Promoter activity was measured by the dual luciferase assay, with 5'-aza-deoxycytidine to examine the effect of demethylation on the expression level of PRKCDBP. RESULTS: The methylation levels of PRKCDBP in tumor tissues and 3 cm para-tumor were higher than those of distant (>10 cm) non-tumor tissues. Receiver operating characteristic (ROC) curve analysis between tumor tissues and distant non-tumor tissues showed that the area under the line (AUC) was 0.717. Dual luciferase experiment confirmed that the promoter region was able to promote gene expression. Meanwhile, in vitro methylation of the fragment (PRKCDBP_Me) could significantly reduce the promoter activity of the fragment. Demethylation of 5'-aza-deoxycytidine in lung cancer cell lines A549 and H1299 showed a significant up-regulation of PRKCDBP mRNA levels. CONCLUSIONS PRKCDBP methylation is a potential and promising candidate biomarker for non-small cell lung cancer.
Biomarkers/metabolism* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Cell Line, Tumor ; DNA Methylation ; Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/genetics* ; Lung Neoplasms/pathology* ; Promoter Regions, Genetic

Objective To explore the safety and long-term results of preoperative imatinib mesylate administration (IM) in patients with locally advanced gastrointestinal stromal tumors (GIST).Methods From Sep 2009 to Nov 2016,locally advanced GIST patients treated in Fujian Medical University Cancer Hospital were analysed retrospectively.Result 34 patients were included.Preoperative median IM treatment was 27 weeks(range 12-71 weeks).65％ patients had a partial response to IM,35％ showed stable disease.All patients underwent surgical R0 resection.The complication rate was 9％ and no death occurred within 30 days post operation.The median follow-up time was 62.2 months (range of 13-89 months).20 patients continued to take imatinib orally,14 patients did not.The 3 year survival rate of patients undergoing surgery was 67％.Univariate analysis showed that tumor location,preoperative imatinib effect,pathology,targeted therapy after surgery were factors affecting prognosis.Multivariate analysis show that the independent risk factors affecting prognosis were tumor location,pathology,targeted therapy after surgery.Conclusion In locally advanced GISTs,preoperative IM is useful and safe that can effectively decrease tumor size,facilitating resection.

Objective: To discuss the application of bedside ultrasound monitoring of gastric residual volume in ICU patients complicated with enteral nutrition support via nasogastric tube. Methods: November 2017 to May 2018, 120 patients with enteral nutrition support via nasogastric tube who admitted in ICU of our hospital were randomly divided into the observation group and the control group. The observation group used bedside ultrasound monitoring to determine the gastric residual volume, while the control group was estimated by withdrawn with 50 ml syringe. Reflux, pulmonary aspiration and the time of enteral nutrition were observed in both groups. Results: Reflux and pulmonary aspiration were present in 2, 3 in the observation group and 10, 11 in the control group, with significant difference between them (χ²=4.53, 3.96, P<0.05). The time of enteral nutrition in the observation group was (13.98±3.20) h, and (15.54±3.54) h in the control group, which had a statistically difference (t=-10.49, P<0.05). Conclusion The application of bedside ultrasound monitoring of gastric residual volume in ICU patients complicated with enteral nutrition support via nasogastric tube can significantly reduce the risk of reflux and pulmonary aspiration which can ensure the safety of enteral nutrition, and decrease time of enteral nutrition.

Yeast cell wall plays an important role in the establishment and maintenance of cell morphology upon the cell wall stress. The cell wall of yeast consists of β-glucans, mannoproteins and chitin. The composition and structure remodel due to cell wall stress. Brewer's yeast cell wall exhibits stress response during long-term acclimation in order to adapt to environmental changes. This paper reviews the composition and structure of yeast cell wall and the molecular mechanisms of cell wall remodeling and signal pathway regulation.
Cell Wall ; Chitin ; Saccharomyces cerevisiae

Objective To explore the application and effectiveness of the combination of bilabial /Φ/and inter-dental /θ/to the training of pronouncing fricatives after cleft palate operations .Methods Seventy children aged four to eight years with abnormal fricatives after cleft palate operations over one month were enrolled in the study . They were randomly allocated into the experimental group (35 cases) and the control group (35 cases) .The chil-dren in the experimental group received the combined training of bilabial /Φ/and inter-dental /θ/while those in the control group received routine rehabilitation training .Results After 6 to 10 times of speech training ,the number of erroneous words of the experimental group decreased to 1 .20 ± 0 .35 from 70 .80 ± 0 .52 before the training .The difference was statistically significant (Z= -5 .215 , P= 0 .001) .The number of incorrect words of the control group decreased to 7 .17 ± 0 .45 from 70 .86 ± 0 .50 of the baseline .The difference was statistically significant (Z=-5 .237 ,P=0 .001) .The number of erroneous words of the two groups had no statistical differences before train-ing (t= -0 .079 ,P=0 .937) .The number of wrong words of the experimental group was significantly lower than the control group after training (Z= -7 .023 ,P=0 .001) .Conclusion The application of the combination of bilabi-al /Φ/and inter-dental /θ/to the training of pronouncing fricatives after cleft palate operations can decrease dis-tinctly the number of erroneous words .

Objective To analyze the risk factors for anastomotic leak after total gastrectomy in gastric cancer patients and its impact on patients survival.Methods A total of 1 547 gastric cancer patients who underwent curative resection between 1999 to 2016 were enrolled.Results The anastomotic leak occurred in 106 of 1 547 patients;and it was happened at a median of (6.0 ± 2.1) day after surgery.The median postoperative hospital stay was (9 ± 3) days for non-anastomotic leak,lower than patients for anastomotic leak with (15 ± 5) days.The anastomotic leak was significantly correlated with age,lung function,BMI,serum albumin,intraoperative blood loss,operative time,smoking and diabetes (P ＜0.05).Multivariable analysis showed that the anastomotic leak was significantly correlated with diabetes,lung function,smoking (P ＜ 0.05).The 30-day mortality with anastomotic leak was lower than patients without leak.The 3'-and 5-year survival rate of patients with anastomotic leak were 53.9％ and 47.7％,significantly lower than those of 69.4％ and 58.5％ without anastomotic leak (P ＜ 0.05).By univariate analysis that BMI,pathological stage,tumor size,serum albumin,anastomotic leak were factors affecting prognosis (P ＜ 0.05).While multivariate analysis showed that anastomotic leakage was independently associated with worse overall survival.Conclusion Anastomotic leakage in patients who underwent total gastrectomy increases the 30-day mortality and associated with poorer 5-year survival.

Objective: To investigate the effect of intracoronary administration of nicorandil prior to primary percutaneous coronary intervention (PPCI) on myocardial perfusion and short-term clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Methods: A total of 158 patients with STEMI undergoing PPCI from January 2014 to December 2015 in Fuzhou General Hospital were enrolled consecutively in this prospective controlled randomized trial. Patients were assigned into three groups with random number table: the nicorandil group (patients received intracoronary administration of 6 mg nicorandil after guide wire or balloon successfully crossed the target lesion, n=53), the nitroglycerin group (patients received intracoronary administration of 300 μg nitroglycerin after after guide wire or balloon successfully crossed the target lesion, n=52) and the control group(patients received routine treatment, n=53). The primary outcomes were myocardial perfusion, including the levels of corrected TIMI frame count (cTFC), and the incidence of no reflow or slow flow after PPCI. The secondary outcomes included the incidence of major adverse cardiovascular events (MACE) during hospitalization (all-cause death, reperfusion arrhythmia within 2 hours after PPCI, angina within 24 hours after PPCI, new heart failure or worsening cardiac function, and repeat revascularization) and within 3 months of follow-up (all-cause death, nonfatal myocardial infarction, repeat revascularization, post-infarction angina, and re-hospitalization for congestive heart failure). Results: The age of enrolled patients was (62.9±11.3) years old, and 130 cases (82.3%) of them were male. The median time of symptom-onset to balloon was 4.50 (3.20, 6.43) hours. There were significantly difference in cTFC immediately after PPCI((21.68±7.43)frames, (24.74±8.66)frames, and(27.06±10.40)frames), incidence of no reflow or slow flow after PPCI(5.7%(3/53), 13.5%(7/52), and 22.6%(12/53)), ST-segment resolution at 2 hours after procedure(90.6%(48/53), 84.6%(44/52), and 74.5%(38/53)), and reperfusion arrhythmia at 2 hours after procedure(15.1%(8/53), 36.6%(19/52), and 34.0%(18/53)) among the 3 groups(P<0.01 or 0.05). In the multivariate logistic regression models, intracoronary administration of nicorandil could lower the cTFC level (OR=0.17, 95%CI 0.10-0.41, P=0.001), acted as a protecting factor on lowering the incidence of no reflow or slow flow (OR=0.13, 95%CI 0.02-0.96, P=0.045) and reperfusion arrhythmia (OR=0.26, 95%CI 0.09-0.74, P=0.012), as well as facilitating the ST-segment resolution at 2 hours after procedure (OR=4.62, 95%CI 1.14-18.82, P=0.033). However, observed parameters were similar between intracoronary administration of nitroglycerin group compared with control group (all P>0.05). MACE within 3 months of follow-up were similar among the 3 groups(all P>0.05). Conclusion Intracoronary administration of nicorandil prior to balloon dilation can significantly improve the myocardial perfusion and reduce the occurrence of reperfusion arrhythmia during PPCI for STEMI, but does not affect the short-term prognosis in STEMI patients.

Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC50 values less than 1 µmol/L in cell-based assays. Here, we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused-ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders.

Objective The aim of this prospective observational study was to analyze the prevalence and the predictive factors of hemorrhagic events after abdominal paracentesis in patients with acute-on-chronic liver failure (ACLF).Methods ACLF patients who received at least one episode of abdominal paracentesis were prospectively enrolled between January 2010 to December 2013. Prevalences of intraperitoneal and abdomen hemorrhage complications were examined. t test was performed for continuous variables and chi-square test was performed for categorical variables.Binary Logistic regression was used to analyze the risk factors of hemorrhage.Results A total of 525 abdominal paracenteses were carried out on 185 ACLF patients within a 4-year period,with 289 (55 .0%)for diagnostic purpose and 236 (45 .0%)for therapeutic purpose.A total of 16 (3.0%)hemorrhagic complications were identified, with 4 cases of abdominal wall hematomas and 12 cases of intraperitoneal hemorrhage.Patients were divided into hemorrhage group and non-hemorrhage group according to this complication.Age,gender, Child-Pugh score,volume of ascitic fluid removed,underlying cirrhosis,platelet count and thrombin time were not significantly different between two groups (all P > 0.05 ).Patients with bleeding events had lower fibrinogen levels and higher prothrombin time,international normalized ratio,activated partial thromboplastin time and model for end-stage liver disease score (all P <0.05).After adjustment of other factors,multivariate regression analysis indicated that low fibrinogen level was the only independent predictor of hemorrhagic complication (OR=0.105,95%CI :0.018-0.608,P =0.012).Conclusion Low fibrinogen level is the independent predictor of severe hemorrhagic complications following paracenteses in patients with ACLF.

Objective To study the expression of interleukin-1β in aortic dissections and aneurysms. Methods Aortic specimens were obtained from patients with type Ⅰ thoracic aortic dissection (11 cases),ascending thoracic aortic aneurysms (10 cases),and healthy organ donors (7 cases).Expression of interleukin-1β,matrix metalloproteinase-9,and signal transduction factors phospho-p38 and phospho-JNK were detected by real time RT-PCR,Western blot,and immunohistochemistry,respectively.TUNEL staining was performed to detect apoptosis of media cells. Results Apoptosis in the media of thoracic aortic dissection and ascending thoracic aortic aneurysms was dramatically higher than control group.Expression of interleukin-1β gradually increased in an order of control group,thoracic aortic dissection to ascending thoracic aortic aneurysms ( P ＜ 0.01,respectively).Expression of matrix metalloproteinase-9significantly increased in the media of thoracic aortic dissection and ascending thoracic aortic aneurysms compared with control group (P ＜ 0.01,respectively).There were positive correlations between interleukin1 β and matrix metalloproteinase-9,interleukin-1β and phospho-p38 in thoracic aortic dissection ( P ＜ 0.01,respectively),interleukin-1β and apoptosis in ascending thoracic aortic aneurysms (P ＜ 0.01 ).Conclusions Interleukin-1β and interferon-γ might effect the formation of thoracic aortic dissection and ascending thoracic aortic aneurysms possibly through the up-regulation of matrix metalloproteinase-9 and apoptosis of media cells in humans.