Objective To study the association of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) promoter region methylation with human esophageal cancer. Methods Promoter region methylation of UCHL1 was dctcctcd by rnethylation specific PCR (MSP) in esophageal cancer cell lines and tissue samples.The expression of UCHL1 was detected by semi-quantitative RT-PCR and Western blot in esophagcal cancer cell lines.5-Aza-2'-deoxycytidine (5-Aza) was applied to reactivate methylated cell lines.ResultsComplete methylation of UCHL1 promoter region was detected in 8 cell lincs (KYSE30,KYSE150,KYSE140,KYSE450,KYSE510,TE3,TE7,TE10).Loss of UCHL1 expression was found in7 cell lines ( KYSE30,KYSE150,KYSE140,KYSE450,KYSE510,TE3,TE7).Reduced expression was found in TE10 cell line. Promoter region hypermethylation was correlated with UCHL1 expression in esophageal cancer cell lines.Re-expression of UCHL1 was induced by 5-Aza treatment in KYSE150 and TE3 cell lines.UCHL1 was frequently methylated in human primary esophageal cancer (74.51％,38/51 ),while no methylation was detected in normal esophageal mucosa (0/10). No association was found between promoter region methylation and age,gender,tumor location,tumor stage or lymph node metastasis.Conclusions UCHL1is silenced by promoter region hypermethylation in human esophageal cancer.Methylation of UCHL1 is frequently happened to primary esophageal cancer and may play an important role in the tumorigenesis.

Objective To investigate the role of GST-? mRNA in the development and pathogenesis of esophageal cancer. Methods Twenty two matched pairs of esophageal cancerous and noncancerous tissues were obtained from 22 patients with esophageal cancer in an endemic region. AP-PCR was used for determining the differential gene fragments and RT-PCR for detecting the expression of GST-? mRNA. Results Differential random amplified fragments were found in 6 cancerous tissues, and none of the noncancerous tissues. The 5T differential gene fragments were of 1.0 kb, and by cloning, sequencing, and sequence homology analysis, no homologous sequence was found in the gene library. The expression rates of GST-? mRNA in cancerous and noncancerous tissues were 54.5%(12/22) and 18.2%(4/22), respectively. Conclusions Whether the 5T differential gene fragment is a new gene candidate or is a marker of oncogene remains to be further studied. The expression of GST-? mRNA in esophageal cancerous tissue was markedly enhanced.

The results of analyzing the managerial characteristics and complexity of product cooperative development suggest that task planning is an important aspect for process management of product cooperative development and the method for planning tasks should be able to model the dependency between tasks and iterations during the development process. In this paper, a DSM-based method and its corresponding optimization algorithms are developed. At first the coupled task sets and uncoupled task setsare identified, and the tasks are then optimized by the corresponding algorithms. The optimal tasks plan will reduce the development time and cost. Considering the practical requirements in real world, a Multilayer DSM is proposed, and its information communication techniques between DSM and traversing principle are described in details.

Objective To investigate the impacts of S-ademetionine (SAM) on cell cycles,apoptosis and invasive capacity of gastric cancer cell lines,and its effects on methylation and expressions of c-myc and uPA.Methods MKN-28,SGC-7901 and MKN-45 cells were treated with gradient concentrations of SAM(0,2 and 4 mmol/L) for 72 hours.The changes of cell cycles and apoptosis were detected by flow eytometry,and invasion was detected by transwell assay.The expressions and methylations of c-myc and uPA were examined by RT-PCR and MSP,respectively.Results The cell apoptosis significantly increased and cell invasive capacity was restrained in three cell lines with increase of SAM concentration (all P values<0.01).In SGC-7901,the cell percentage of G0/G1 phase significantly increased [(74.53±2.49)% vs.(56.67±1.18)%,P<0.053,whereas the cell proliferation index (PI) decreased [(25.50±2.46)% vs.(43.33±1.18)%,P<0.05] in comparison with controls.The expressions of c-myc and uPA mRNA in SGC-7901,uPA mRNA in MKN-45 and in 4 mmol/L SAM treated MKN-28 significantly decreased.The methylations of c-myc gene in SGC-7901 and uPA gene in three cell lines were reversed after treated with SAM.Conclusions SAM reduces expressions of c-myc and uPA by reversing the methylations of c-myc in SGC-7901 and uPA in all three cell lines.However SAM,as methyl donor,can restrain the development and progression of tumor when hypomethylation widely presents in cancer.

Objective To summarize and analyze the clinical characteristic of blue rubber bleb nevus syndrome (BRBNS).Methods The clinical data of four cases treated since 2001 and 30 BRBNS cases reported by domestic literature were retrospectively analyzed.The clinical manifestation,family history,endoscopy and imageology examination,site of lesions,treatment and follow up were analyzed.Results The male to female ratio was 1.8∶1 and median age was 19.5 years.A total of 33 cases (97.1％) presented with gastrointestinal bleeding,median age of gastrointestinal bleeding detected was 9.0 years.Among the 33 cases,anemiawas found as the primary symptom in nine cases (27.3％),and one case complicated with intussusception and intestinal necrosis accompanied with abdominal pain.Two cases have family history.Gastroscopy (85.3 ％) and colonoscopy(73.5 ％) were mainly examinations for detection.Lesions mainly involved skin (100.0％) and digestive tract (97.1％),and the locations of the lesion in digestive tract was stomach (64.7％),small intestine (64.7％),colon (58.8％),esophagus (29.4％).Treatment methods included symptomatic treatment,endoscopic therapy and surgery.Banding ligation and polypectomy resection were common endoscopic therapies.Gastrointestinal bleeding did not recur in six cases with endoscopic therapy and four cases receiving surgery during short-term follow up.Conclusions BRBNS lesions mainly involve skin and digestive tract,mostly complicated with gastrointestinal bleeding.For gastrointestinal bleeding,so far endoscopic therapy and surgery are the effective therapies.

Epigenetic changes frequently occur in human colorectal cancer. Genomic global hypomethylation, gene promoter region hypermethylation, histone modifications, and alteration of miRNA patterns are major epigenetic changes in colorectal cancer. Loss of imprinting(LOI) is associated with colorectal neoplasia. Folate deficiency may cause colorectal carcinogenesis by inducing gene-specific hypermethylation and genomic global hypomethylation. HDAC inhibitors and demethylating agents have been approved by the FDA for myelodysplastic syndrome and leukemia treatment. Non-coding RNA is regarded as another kind of epigenetic marker in colorectal cancer. This review is mainly focused on DNA methylation, histone modification, and microRNA changes in colorectal cancer.
Colorectal Neoplasms ; genetics ; metabolism ; CpG Islands ; genetics ; DNA Methylation ; Epigenesis, Genetic ; Folic Acid Deficiency ; genetics ; Genomic Imprinting ; Histone Deacetylase Inhibitors ; metabolism ; Histone Deacetylases ; metabolism ; Histones ; metabolism ; Humans ; MicroRNAs ; genetics ; metabolism ; Promoter Regions, Genetic ; genetics ; RNA, Untranslated ; genetics ; metabolism

This study investigated the tight junction (TJ) protein expression of the intestinal mucosa in a rat tail-suspension model under simulated weightlessness. Twenty-four Wistar rats were randomly divided into three groups: CON group (n=8), control; SUS-14 d group (n=8), tail-suspension for 14 days; SUS-21 d group (n=8), tail-suspension for 21 days. Occludin and Zonula Occluden-1 (ZO-1) expression levels were determined by immunohistochemical analysis and mRNA fluorescent quantitative PCR. Plasma levels of diamine oxidase (DAO) and d-lactate were determined using enzymatic spectrophotometry. Immunohistochemical results for occludin and ZO-1 showed disruption of the TJs in the intestinal mucosa in SUS-14 d and SUS-21 d groups. The expression levels of occludin and ZO-1 in SUS-21 d group were lower than those in SUS-14 d group, and significantly lower than those in CON group (Occldin: 0.86±0.02 vs 1.01±0.03 vs 1.63±0.03 and ZO-1: 0.82±0.01 vs 1.00±0.02 vs 1.55±0.01, P<0.01). Moreover, the levels of plasma DAO and d-lactate in SUS-21 d group were higher than those in SUS-14 d group, and significantly higher than those in CON group (DAO: 27.58±0.49 vs 20.74±0.49 vs 12.94±0.21 and d-lactate: 37.86±0.74 vs 28.26±1.01 vs 17.76±0.91, P<0.01). There were significant negative correlations between occludin or ZO-1 expression levels and DAO (r (2)=0.9014, r (2)=0.9355, P<0.01) or d-lactate levels (r (2)=0.8989, r (2)=0.9331, P<0.01). Occludin and Zo-1 were reduced in intestinal mucosa both in mRNA and protein levels in the rat tail-suspension model. The significant negative correlations between expression levels of TJs and plasma levels of DAO or d-lactate support the hypothesis that intestinal permeability is increased due to a decrease in TJ protein expression during tail-suspension from 14 days to 21 days.

Background::Asthma imposes a large healthcare burden in China and the United States (US). However, the trends of asthma mortality and the relative risk factors have not been comparatively analyzed between the countries. The aim of this study was to compare the mortality and risk factors between China and the US.Methods::The deaths, and mortality rates of asthma in China and the US during 1990–2019 were obtained from the Global Burden of Disease Study 2019. The age–period–cohort model was used to estimate these mortality rates based on a log-linear scale with additive age, period, and cohort effects. The population attributable fractions of risk factors for asthma were estimated.Results::In 1990–2019, the asthma mortality rate was higher in China than in the US. The crude and age-standardized asthma mortality rates trended downward in both China and the US from 1990 to 2019. The decline in mortality was more obvious in China. Mortality gap between the two countries was narrowing. A sex difference in asthma mortality was observed with higher mortality in males in China and females in the US. The age effects showed that mortality increased with age in adults older than 20 years, particularly in the elderly. Downward trends were generally observed in the period and cohort rate ratios in both countries, with China experiencing a more obvious decrease. Smoking and high body mass index (BMI) were the leading risk factors for asthma mortality in China and the US, respectively. Mortality attributable to occupational asthmagens and smoking decreased the most in China and the US, respectively.Conclusions::In 1990–2019, the asthma mortality rate was higher in China than in the US; however, the mortality gap has narrowed. Mortality increased with age in adults. The improvements in asthma death risk with period and birth cohort were more obvious in China than in the US. Smoking, high BMI, and aging are major health problems associated with asthma control. The role of occupational asthmagens in asthma mortality underscores the importance of management and prevention of occupational asthma.

Objective To construct and evaluate the rat model of thyroid nodule liver-qi depression syndrome with the combination of disease and syndrome,so as to lay a foundation for the exploration of the mechanism and clinical research of traditional Chinese medicine in the treatment of thyroid nodule.Methods 36 rats were randomly divided into three groups.The model was induced by chronic unpredictable mild stress(CUMS)stimulation combined with propylthiouracil(PTU).The rats in the blank group were fed with saline at the dose of 1 mL·100 g-1·d-1,and the rats in the PTU group were fed with 0.1%PTU solution at the dose of 1 mL·100 g-1·d-1.The rats in the CUMS+PTU group were fed with CUMS stimulation in a single cage and intragastric administration of 0.1%PTU solution according to the dose of 1 mL·100 g-1·d-1,and the modeling time lasted for 6 weeks.After the establishment of the model,the model of combination of disease and syndrome was evaluated comprehensively by means of animal behavior detection,ultrasonic image,apparent morphology observation,pathological staining and serum hormone index detection.Results Compared with control group and PTU group,the total distance in the open field was significantly shortened,the sucrose preference rate was significantly decreased,and the swimming suspension time was significantly prolonged in the CUMS+PTU group,showing obvious symptoms of liver qi stagnation.In addition,compared with the other two groups,the thyroid gland of CUMS+PTU group showed obvious enlargement and nodule formation,thyroid index significantly increased,and thyroid follicular epithelial cells showed a high phase of proliferation.In terms of hormone levels,compared with control group,the serum levels of free triiodothyronine(FT3)and free thyroxine(FT4)in CUMS+PTU group were significantly lower,while the level of thyroid stimulating hormone(TSH)was significantly higher,which was in line with the current evaluation criteria of thyroid nodule model.Conclusion The method of CUMS stimulation combined with PTU drug induction can successfully prepare the rat model of thyroid nodule liver-qi depression syndrome,and the comprehensive evaluation method is stable and reliable,which is helpful to improve the scientific nature of the disease-syndrome combination model.

This study investigated the tight junction (TJ) protein expression of the intestinal mucosa in a rat tail-suspension model under simulated weightlessness.Twenty-four Wistar rats were randomly divided into three groups:CON group (n=8),control; SUS-14 d group (n=8),tail-suspension for 14 days;SUS-21 d group (n=8),tail-suspension for 21 days.Occludin and Zonula Occluden-1 (ZO-1) expression levels were determined by immunohistochemical analysis and mRNA fluorescent quantitative PCR.Plasma levels of diamine oxidase (DAO) and d-lactate were determined using enzymatic spectrophotometry.Immunohistochemical results for occludin and ZO-1 showed disruption of the TJs in the intestinal mucosa in SUS-14 d and SUS-21 d groups.The expression levels of occludin and ZO-1 in SUS-21 d group were lower than those in SUS-14 d group,and significantly lower than those in CON group (Occldin:0.86±0.02 vs 1.01±0.03 vs 1.63±0.03 and ZO-1:0.82±0.01 vs 1.00±0.02 vs 1.55±0.01,P＜0.01).Moreover,the levels of plasma DAO and d-lactate in SUS-21 d group were higher than those in SUS-14 d group,and significantly higher than those in CON group (DAO:27.58±0.49 vs 20.74±0.49 vs 12.94±0.21 and d-lactate:37.86±0.74 vs 28.26±1.01 vs 17.76±0.91,P＜0.01).There were significant negative co rrelations between occludin or ZO-1 expression levels and DAO (r2=0.9014,r2=0.9355,P＜0.01) or d-lactate levels (r2=0.8989,r2=0.9331,P＜0.01).Occludin and Zo-1 were reduced in intestinal mucosa both in mRNA and protein levels in the rat tail-suspension model.The significant negative correlations between expression levels of TJs and plasma levels of DAO or d-lactate support the hypothesis that intestinal permeability is increased due to a decrease in TJ protein expression during tail-suspension from 14 days to 21 days.