Secular trends of asthma mortality in China and the United States from 1990 to 2019 / 中华医学杂志(英文版)

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.

High frequency of alternative splicing variants of the oncogene Focal Adhesion Kinase in neuroendocrine tumors of the pancreas and breast / 医学前沿

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK6/7 in cells. These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.

Effect of the location and size of region of interest on the measurement of liver fat content by QCT / 中华健康管理学杂志

Objective:To explore the effect of the location and size of region of interest (ROI) on the measurement of liver fat by means of quantitative computed tomography (QCT).Methods:A total of 98 subjects who were examined with QCT for bone mineral density examination from December 25, 2019 to January 17, 2020 were recruited continuously from the Department of Health Management of Henan Provincial People′s Hospital. The liver fat content was measured by QCT workstation. The ROI was located respectively in the left lobe, the right anterior lobe and the right posterior lobe of the liver, and it was measured independently by the A measurer and B measurer. The central position of the ROI was fixed and the diameter was increased, and it was measured by the A measurer. In this study, Friedman test was used to compare the differences of measurement results in different positions or sizes of ROI, and intra-class correlation coefficients (ICC) was used to evaluate the repeatability of inter-measurers.Results:There was a significant difference for liver fat content under different positions of ROI (χ2=62.306, P<0.001), but no difference under different seizes of ROI (χ2=1.088, P=0.581). The ICC values of the inter-measurers repeatability analysis of the A measurer and B measurer in the left lobe, right anterior lobe and right posterior lobe of the liver were 0.847, 0.917 and 0.874, all more than 0.75, and the reproducibility was good. Conclusions:When QCT technique is applied to the measurement of liver fat content, the location conditions of ROI may affect results, so it is necessary to select multiple ROI in the whole liver for measurement. The inter-measurers repeatability of QCT in different parts of the liver is good.

Reproducibility of liver fat content measured using quantitative computed tomography / 中华健康管理学杂志

Objective:To provide support for the clinical application of quantitative computed tomography (QCT) in the measurement of liver fat content, this study evaluated the intra-observer and inter-observer reproducibility of liver fat content measured by QCT in a population receiving physical examinations.Methods:From April to July 2019, 291 people were consecutively selected who underwent QCT examination in the health management department of Henan Provincial People′s Hospital. There were 214 males (73.5%) and 77 females (26.5%), aged 48.7±11.0. We measured liver fat content by QCT workstation. Three observers (A, B, C) measured their liver fat content independently, then observer A performed re-testing two weeks later. The mean value of the two measurements from observer A was taken as the final result. Measurement data were described by mean±SD. Intra-observer and inter-observer reproducibility were assessed using intra-class correlation coefficients ( ICC). Results:The first measurement result for observer A was 10.46±5.55 and the second measurement for observer A was 10.66±5.59, resulting in a final value of 10.56±5.51. The measurement results of observers B and C were 10.70±5.45 and 10.86±5.77, respectively. The ICC value of liver fat content values measured by the three observers was 0.960 (95% CI: 0.951-0.967, P<0.001) and the ICC value of liver fat content values for the two measurements of observer A was 0.953 (95% CI: 0.941-0.962, P<0.001). The ICC values were>0.75, so reproducibility of results was good. Conclusions:If the measurement method is consistent, the results for liver fat content measured by a conventional CT scanner and QCT workstation will have good reproducibility between and within observers, and will also have certain clinical application prospects.

Epigenetic changes in colorectal cancer / 癌症

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.

Clinical analysis of thirty-four blue rubber bleb nevus syndrome cases / 中华消化杂志

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.

The role of hypermethylation in promoter region of ubiquitin carboxyl-terminal hydrolase L1 in human esophageal cancer / 中华内科杂志

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.

Effects of simulated weightlessness on tight junction protein occludin and Zonula Occluden-1 expression levels in the intestinal mucosa of rats / 华中科技大学学报（医学）（英德文版）

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.

Effects of S-ademetionine on proliferation of gastric cancer cell lines and methylation of c-myc and uPA genes / 中华消化杂志

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.

Differential gene analysis and expression of GST-? mRNA in esophageal cancerous and noncancerous tissues / 中华消化杂志

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.