AIM:To investigate the effects of epal-restat(Epa)on the mitochondrial oxidative stress damage of radiation pneumonitis(RP)mice and to explore its possible mechanism.METHODS:C57BL/6 mice were randomly divided into control(CON),Irradiation(IR),IR combined with Epa(10 mg/kg)and IR combined with Epa(20 mg/kg)group,16 mice in each group.Mouse models of RP were es-tablished by whole thorax irradiation at a dose of 15Gy using a 6-MV linear accelerator.Continuous intragastric administration after IR for 6 or 8 weeks.Lung histopathology was analyzed by HE staining.The expression of aldose reductase(AR)was deter-mined by immunohistochemistry.Mitochondrial morphology of lung tissues was observed by trans-mission electron microscopy.The levels of inflam-matory cytokines(IL-6,TNF-α and TGF-β1)in plas-ma were detected by ELISA.The contents of Malo-ndialdehyde(MDA)and 4-hydroxynonenal(4-HNE)in lung tissues were determined by colorimetry.Sin-gle cell suspension of lung tissues was prepared and reactive oxygen species(ROS)levels in the cells was examined using a DCFH-DA fluorescent probe.Real-time quantitative PCR was used to determine the expression of AR,IL-6,TNF-α and TGF-β1.The protein levels of AR,IL-6,TNF-α,TGF-β1,BAX,Bcl2,Cleaved Caspase-3,8-oxoguanine DNA glycosylase 1(OGG1)and silent information regulator 3(SIRT3)were detected by Western blot analysis.RESULTS:Compared with the CON group,the alveolar hyper-plasia,alveolar septum thickening and inflammato-ry cell infiltration were observed in the IR group.Moreover,the content of inflammatory factors such as IL-6,TNF-α and TGF-β1 and the expression of BAX and Cleaved Caspase-3 were significantly in-creased,and the expression of Bcl2 was obviously decreased after irradiation.Compared with the IR group,Epa robustly alleviated RP.Meanwhile,Epa down-regulated inflammatory cells infiltration and the expression of inflammatory cytokines,such as IL-6,TNF-α and TGF-β1.In addition,Epa could down-regulate the expression of BAX and Cleaved Caspase-3,and up-regulate Bcl2 in lung tissues.Compared with the CON group,the expression of AR,the levels of ROS,MDA and 4-HNE were signifi-cantly increased,the expression of OGG1 and SIRT3 were significantly decreased,and mitochon-drial damage was aggravated in the IR group.Com-pared with IR group,the expression of AR was sig-nificantly down-regulated,the levels of ROS,MDA and 4-HNE were significantly decreased,the expres-sions of OGG1 and SIRT3 were significantly in-creased,and the mitochondrial damage was signifi-cantly alleviated in IR group after 6 to 8 weeks of Epa administration.CONCLUSION:Epa has a pro-tective effect on RP,which may be related to the in-hibition of AR expression,the reduction of mito-chondrial oxidative stress injury,and the inhibition of inflammatory response and cell apoptosis.

Background::Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys. Methods::This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models. Results::A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69] vs. 35.0% [28/80] vs. 51.8% [29/56], P <0.001). In the univariable competing risk analysis, the cumulative regression rate was statistically significantly lower ( P = 0.008), while the cumulative progression rate was higher ( P = 0.017) in ESCdys patients with CDKN2A deletion than in those without CDKN2A deletion. CDKN2A deletion was also an independent predictor of prognosis in ESCdys ( P = 0.004) in the multivariable analysis. Conclusion::The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.

Humans ; Esophageal Squamous Cell Carcinoma/pathology* ; Esophageal Neoplasms/pathology* ; Carcinoma, Squamous Cell/pathology* ; Precancerous Conditions/pathology* ; Early Diagnosis

BACKGROUND: Family clustering of esophageal cancer (EC) has been found in high-risk areas of China. However, the relationships between cancer family history and esophageal cancer and precancerous lesions (ECPL) have not been comprehensively reported in recent years. This study aimed to provide evidence for identification of high-risk populations. METHODS: This study was conducted in five high-risk areas in China from 2017 to 2019, based on the National Cohort of Esophageal Cancer. The permanent residents aged 40 to 69 years were examined by endoscopy, and pathological examination was performed for suspicious lesions. Information on demographic characteristics, environmental factors, and cancer family history was collected. Unconditional logistic regression was applied to evaluate odds ratios between family history related factors and ECPL. RESULTS: Among 33,008 participants, 6143 (18.61%) reported positive family history of EC. The proportion of positive family history varied significantly among high-risk areas. After adjusting for risk factors, participants with a family history of positive cancer, gastric and esophageal cancer or EC had 1.49-fold (95% confidence interval [CI]: 1.36-1.62), 1.52-fold (95% CI: 1.38-1.67), or 1.66-fold (95% CI: 1.50-1.84) higher risks of ECPL, respectively. Participants with single or multiple first-degree relatives (FDR) of positive EC history had 1.65-fold (95% CI: 1.47-1.84) or 1.93-fold (95% CI: 1.46-2.54) higher risks of ECPL. Participants with FDRs who developed EC before 35, 45, and 50 years of age had 4.05-fold (95% CI: 1.30-12.65), 2.11-fold (95% CI: 1.37-3.25), and 1.91-fold (95% CI: 1.44-2.54) higher risks of ECPL, respectively. CONCLUSIONS: Participants with positive family history of EC had significantly higher risk of ECPL. This risk increased with the number of EC positive FDRs and EC family history of early onset. Distinctive genetic risk factors of the population in high-risk areas of China require further investigation. TRIAL REGISTRATION ChiCTR-EOC-17010553.
Case-Control Studies ; China/epidemiology* ; Esophageal Neoplasms/pathology* ; Humans ; Precancerous Conditions/pathology* ; Risk Factors ; Stomach Neoplasms

Objective:To investigate the association of WWP2 single nucleotide polymorphism (rs3790088, rs4247109) with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) , and explore the influences of DEACMP genetic predisposition. Methods:From November 2006 to December 2017, 235 DEACMP cases and 429 acute carbon monoxide poisoning (ACMP) cases were selected. All ACMP patients were followed up for more than 90 days without DEACMP. The DNA in all blood samples were extracted with the blood Genome DNA Extraction Kit. The method of Sequenom Mass Array SNP technique was used to detect the genotype and allele of WWP2. All DEACMP patients were assessed every 3 days after hospitalization by the Hasegawa Dementia Scale (HDS) and Activity of Daily Living Scale (ADL) . The distribution of genotypes in conformty with Hardy-Weinderg law was analyzed by goodness-of-fit χ 2 test, and χ 2 test was used for association analysis. Results:For rs3790088, there were 226 DEACMP cases and 414 ACMP cases. For rs4247109, there were 234 DEACMP cases and 428 ACMP cases. For rs3790088 and rs4247109 in WWP2 gene: there were not significant differences in the gene genotype distribution and allele frequency of both DEACMP group and ACMP group ( P>0.05) . According to gender, there were not significant differences in WWP2 gene genotype distribution and allele frequency between two female groups and two male groups ( P>0.05) . After analysis by genetic model, the genotype distributions in both DEACMP group and ACMP group were not significantly differences in three genetic models (codominant genetic model, recessive genetic model and dominant genetic model, P>0.05) . Conclusion:It has not confirmed the genetic correlation between the two gene single nucleotide polymorphisms (rs3790088, rs4247109) of WWP2 gene and the incidence of DEACMP.

Objective:To investigate the association of WWP2 single nucleotide polymorphism (rs3790088, rs4247109) with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) , and explore the influences of DEACMP genetic predisposition. Methods:From November 2006 to December 2017, 235 DEACMP cases and 429 acute carbon monoxide poisoning (ACMP) cases were selected. All ACMP patients were followed up for more than 90 days without DEACMP. The DNA in all blood samples were extracted with the blood Genome DNA Extraction Kit. The method of Sequenom Mass Array SNP technique was used to detect the genotype and allele of WWP2. All DEACMP patients were assessed every 3 days after hospitalization by the Hasegawa Dementia Scale (HDS) and Activity of Daily Living Scale (ADL) . The distribution of genotypes in conformty with Hardy-Weinderg law was analyzed by goodness-of-fit χ 2 test, and χ 2 test was used for association analysis. Results:For rs3790088, there were 226 DEACMP cases and 414 ACMP cases. For rs4247109, there were 234 DEACMP cases and 428 ACMP cases. For rs3790088 and rs4247109 in WWP2 gene: there were not significant differences in the gene genotype distribution and allele frequency of both DEACMP group and ACMP group ( P>0.05) . According to gender, there were not significant differences in WWP2 gene genotype distribution and allele frequency between two female groups and two male groups ( P>0.05) . After analysis by genetic model, the genotype distributions in both DEACMP group and ACMP group were not significantly differences in three genetic models (codominant genetic model, recessive genetic model and dominant genetic model, P>0.05) . Conclusion:It has not confirmed the genetic correlation between the two gene single nucleotide polymorphisms (rs3790088, rs4247109) of WWP2 gene and the incidence of DEACMP.

Objective: To estimate the morbidity and mortality of gastric cancer and its distribution in China in 2015 and provide information for future cancer prevention and control study and policy decision. Methods: In 2018, a total of 501 cancer registry systems reported data to the office of National Central Cancer Registry, and the data from 368 cancer registry systems met the criteria. The overall, gender specific, age specific and area specific morbidity and mortality rates of gastric cancer in China were estimated based on national population data in 2015. Chinese standard population in 2000 and World Segi’s population data were used to calculate the age-standardized rates (ASR) of morbidity and mortality, including ASR of China and the world. Results: In 2015, the qualified 368 cancer registry system covered a total of 309 553 499 population in China, including 156 934 140 males and 152 619 359 females. We estimated that there were 403 000 new gastric cancer cases, with the crude morbidity rate of 29.31 per 100 000, ASR China of 18.68 per 100 000, ASR world of 18.57 per 100 000, and a cumulative rate of 2.29% for 0-74 years. There were 290 900 new gastric cancer deaths, with the crude mortality rate of 21.16 per 100 000, ASR China of 13.08 per 100 000, ASR world of 12.92 per 100 000, and a cumulative rate of 1.5% for 0-74 years. Gastric cancer ranked second as the most common cancers and third as the most common cancer causes of death in China. In general, both the morbidity rate (ASR China, male: 26.54 per 100 000; female: 11.09 per 100 000; rural area: 21.82 per 100 000; urban area: 16.37 per 100 000) and mortality rate (ASR China, male: 18.75 per 100 000; female: 7.72 per 100 000; rural area: 15.84 per 100 000; urban area: 11.05 per 100 000) were higher in males than those in females, and higher in rural area than those in urban area. The morbidity and mortality rates of gastric cancer increased from the age of 40 years and peaked in age group of 80-years. The case number of gastric cancer significantly increased from the age group of 50-years, peaked at 60-70 years, and the majority of cases occured in age group of 55-80 years. There was an overall consistent trend of the age-specific morbidity and mortality rates across different subgroups by sex and geographic areas, with the rates were higher in males than those in females, and higher in rural area than that in urban area. Conclusions The incidence of gastric cancer varied with sex, age and areas (urban area and rural area). The present analysis provides the latest data on the prevalence of gastric cancer in China, which can help optimize the current screening guidelines and the prevention and control strategies of gastric cancer to reduce the disease burden caused by gastric cancer in China.

Objective: To estimate the incidence and mortality rates of esophageal cancer in China in 2015. Methods: Based on the data quality review and assessment, the esophageal cancer data from 368 cancer registries in 31 provinces (autonomous regions and municipalities) in China were included in this study. According to the national population data in 2015, the nationwide incidence and mortality of the esophageal cancer were estimated. Chinese standard population in 2000 and world Segi′s population were used to calculate the age-standardized (ASR) incidence and mortality rates (ASR China and world, respectively). Results: The 368 cancer registries covered a total of 309 553 499 populations in China, accounting for 22.52% of the national population. There were 245 651 new esophageal cancer cases estimated in China in 2015, with a crude incidence rate of 17.87/100 000. The ASR China and ASR world were 11.14/100 000 and 11.28/100 000, respectively. The estimated number of esophageal cancer death was 188 044 in China in 2015, with a crude mortality rate of 13.68/100 000; The ASR China and ASR world mortality rates were 8.33/100 000 and 8.36/100 000, respectively. The ASR China incidence and mortality of esophageal cancer in males were higher in males (16.50/100 000 and 12.66/100 000) than those in females (5.92/100 000 and 4.17/100 000), and they were higher in rural areas (15.95/1100 000 and 11.67/100 000) than those in urban areas (7.59/100 000 and 5.87/100 000). Conclusion The incidence and mortality of esophageal cancer in China are higher than the global average. The disparity of the incidence and mortality rates of esophageal cancer significantly differed in genders and areas.

Objective: Data from local cancer registries were pooled to estimate cancer incidence and mortality in China, 2015. Methods: Data submitted from 501 cancer registries were checked & evaluated according to the criteria of data quality control, and 368 registries′ data were qualified for the final analysis. Data were stratified by area (urban/rural), sex, age group and cancer sites, and combined with national population data to estimate cancer incidence and mortality in China, 2015. Chinese population census in 2000 and Segi′s population were used for age-standardized. Results: Total population covered by 368 cancer registries were 309 553 499 (148 804 626 in urban and 160 748 873 in rural areas). The percentage of morphologically verified cases (MV) and the percentage of death certificate-only cases (DCO) accounted for 69.34% and 2.09%, respectively, and the mortality to incidence ratio was 0.61. About 3 929 000 new cancer cases were reported in 2015 and the crude incidence rate was 285.83 per 100 000 population (males and females were 305.47 and 265.21 per 100 000 population). Age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 190.64 and 186.39 per 100 000 population, respectively, with the cumulative incidence rate (0-74 age years old) of 21.44%. The cancer incidence and ASIRC were 304.96/100 000 and 196.09/100 000 in urban areas and 261.40/100 000 and 182.70/100 000 in rural areas, respectively. About 2 338 000 cancer deaths were reported in 2015 and the cancer mortality was 170.05/100 000 (210.10/100 000 in males and 128.00/100 000 in females). Age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 106.72/100 000 and 105.84/100 000, respectively, with the cumulative incidence rate (0-74 age years old) of 11.94%. The cancer mortality and ASMRC were 172.61/100 000 and 103.65/100 000 in urban areas and 166.79/100 000 and 110.76/100 000 in rural areas, respectively. The most common cancer cases including lung, gastric, colorectal, liver and female breast, the top 10 cancer incidence accounted for about 76.70% of all cancer new cases. The most common cancer deaths including lung, liver, gastric, esophageal and colorectal, the top 10 cancer deaths accounted for about 83.00% of all cancer deaths. Conclusions The burden of cancer showed a continuous upward trend in China. Cancer prevention and control faces the problem of the disparity in different areas and different cancer burden between men and women. The cancer pattern in China presents the coexistence of the cancer patterns in developed and developing countries. The situation of cancer prevention and control is still serious in China.

Objective: Using updated population-based cancer registration (PBCR) data, we estimated nation-wide liver cancer statistics overall, by sex and by areas in China. Methods: Qualified PBCR data of liver cancer in 2015 which met the data quality criteria were stratified by geographical locations, sex, and age groups. Age-specific incidence and mortality rates by sex and area were calculated. The burden of liver cancer was evaluated by multiplying these rates by the year of 2015 population. Chinese standard population in 2000 and World Segi′s population were used for the calculation of age-standardized rates (ASR) of incidence and mortality. Results: Qualified 368 cancer registries covered a total of 309 553 499 populations in China, accounting for 22.52% of the national population. It is estimated that there were 370 000 new cases (274 000 males and 96 000 females) of liver cancer in China. The age-standardized incidence rates by Chinese standard population (ASR China) and World Segi′s population (ASR World) were 17.64 per 100 000 and 17.35 per 100 000, respectively. Rural areas showed higher incidence (ASR China: 20.07 per 100 000, ASR World: 19.67 per 100 000) than urban areas (ASR China: 15.90 per 100 000, ASR world: 15.67 per 100 000). Subgroup analysis showed that western areas of China had highest incidence rate of liver cancer, with the ASR China of 20.65 per 100 000 and 20.22 per 100 000 for ASR world, respectively. For new cases of liver cancer deaths, there were 326 000 new deaths (242 000 males and 84 000 females) in China, with age-standardized mortality rate by Chinese standard population and World Segi′s population of 15.33 per 100 000 and 15.09 per 100 000, respectively. Rural areas showed higher mortality (ASR China: 17.17 per 100 000, ASR world: 16.86 per 100 000) than urban areas (ASR China: 14.00 per 100 000, ASR World: 13.81 per 100 000). Conclusions There is still a heavy burden of liver cancer in China. Rural residents have higher incidence and mortality of liver cancer compared with urban counterparts. It is likely that many factors such as hepatitis virus infection, and aflatoxin exposure play a dominating role. Prevention and control strategies should be enhanced in the future.