[Regional disparities in trends of global gastric cancer incidence and mortality from 1990 to 2019].

Objective: To depict gastric cancer burden trends globally and analyze geographical and socioeconomic disparities among different countries and territories. Methods: We extracted the data from Global Burden of Disease 2019 Database. We conducted the Joinpoint regression and calculated the average annual percent change (AAPC) and corresponding 95% confidence interval (CI) for age-standardized gastric cancer incidence and mortality from 1990 to 2019. Linear regression was performed to measure the association of sociodemographic index (SDI) with each country's gastric cancer incidence and mortality AAPC. We applied the age-period-cohort analysis to assess the cohort effect on gastric cancer incidence and mortality. Results: The AAPCs for gastric cancer age-standardized incidence and mortality rates from 1990 to 2019 were -1.27% (95% CI: -1.43%, -1.11%) and -1.87% (95% CI: -2.01%, -1.72%), respectively. SDI levels were negatively associated with AAPCs, which means that countries with higher SDI had higher AAPC (P<0.001). The decrease of gastric cancer burden in countries with low or medium SDI levels was slower than that globally. The age-period-cohort analysis indicated that countries with higher SDI levels had more apparent decline in birth cohort effects from 1900 to 1999. Conclusions: Countries with different socioeconomic levels have various decreasing rates for gastric cancer incidence and deaths. Countries with higher SDI levels have higher declining rates for gastric cancer burden.

[A comparative analysis of the distribution of the high-risk population of upper gastrointestinal cancer and endoscopic screening compliance in two urban areas and two rural areas in China].

Objective: To analyze and compare the distribution of the high-risk population of upper gastrointestinal (UGI) cancer and the factors influencing the compliance rate of endoscopic screening in urban China and rural China. Methods: From 2015 to 2017, an epidemiological survey was conducted on residents aged 40-69 in two rural areas (Luoshan county of Henan province, Sheyang county of Jiangsu province) and two urban areas (Changsha city of Hunan province, Harbin city of Heilongjiang province). As a result, high-risk individuals were recommended for endoscopic screening. Chi-square χ(2) test was used to compare the high-risk rate of UGI cancer between urban and rural residents. In addition, the multivariate logistic regression model was used to analyze the factors influencing the compliance rate of endoscopic screening. Results: A total of 48, 310 residents aged 40-69 were enrolled in this study, including 22 870 (47.34%) residents from rural areas and 25 440 (52.66%) residents from urban areas. A total of 23 532 individuals were assessed with a high risk of UGI cancer, with an overall risk rate of 48.71%. A higher proportion of participants with high risk was observed in rural China (56.17%, 12 845/22 870) than in urban China (42.01%, 10 687/25 440). A total of 10 971 high-risk individuals with UGI cancer participated in endoscopic screening, with an overall compliance rate of 46.62% (10 971/23 532), 45.15% (5 799/12 845) in rural China, and 48.40% (5 172/10 687) in urban China. In rural population, the compliance rate of endoscopic screening was higher in those of females, aged 50-69 years, primary school education or above, high income, a family history of UGI cancer, history of gastric and duodenal ulcer, history of reflux esophagitis, and history of superficial gastritis, but lower in smokers (P<0.05). Among the urban population, the compliance rate of endoscopic screening was higher in those aged 40-49 years, uneducated, low income, family history of UGI cancer, history of reflux esophagitis, history of superficial gastritis, but lower in smokers (P<0.05). Conclusions: The proportion of participants with high risk of UGI cancer in rural areas is higher than that of urban areas. The compliance rates of endoscopic screening in urban and rural areas are low, and influencing factors of endoscopic screening exhibit some differences in rural China and urban China.

[Access to liver cancer screening and surveillance in populations in China: an exploratory analysis].

Objective: To systematically quantify the access to screening and surveillance service of liver cancer in populations in China, especially a series of sub-indicators of the availability. Methods: Following the specific indicators applied by the International Agency for Research on Cancer in the session of availability and use of screening practices in several cancer screening handbooks, information about the access/availability of liver cancer screening and surveillance in population in China were collected; the indicators included local policies and guidelines, procedures most commonly used or recommended, population coverage and participation rate, compliance and related factors, treatment rate, acceptability, equity and others. Systematic review approach was used, combined with searching core literatures/monograph, websites of governments and available program reports, for a systematic analysis on the access to liver cancer screening and surveillance in populations in China. Results: A total of 34 journal articles were included from the systematic review and most of which were about the participation of secondary liver screening or surveillance compliance; additional information were mainly obtained from the other sources. Overall, there were clearly recommended screening and surveillance procedures for liver cancer in the three major cancer screening programs funded by the central government of China. It was estimated that 0.09% of the population aged 35-74 years were covered by liver cancer screening in 2019 in China. The overall participation rates of secondary screening ranged from 37.5% to 62.3% in three major programs, the median compliance rate of surveillance was reported as 26.9% (Q1,Q3: 23.5%, 41.0%) in the 6 included studies. Two studies reported the factors affecting the participation and compliance. A large-scale multicenter analysis showed that the subject acceptability to alpha fetoprotein test combined with ultrasound screening was as high as 99.3% in high-risk population in urban area. The treatment rate of liver cancer founded by screening, surveillance or follow-up was estimated to be >90% in rural population. No studies of equity were obtained via the systematic review. Conclusions: The public health service programs in China all recommend specific procedures for liver cancer screening in general population and surveillance for high-risk individuals. However, the overall availability needs to be improved, particularly in the indicator of population coverage. Participation rates of screening and compliance rates of surveillance varied among the included programs and the studies, suggesting that the influencing factors need to be further identified. The relatively high subject acceptability suggests the potential demands for screening service. More efforts are needed to address the access to screening and surveillance of liver cancer in populations in China.

[DALYs for breast cancer in China, 2000-2050: trend analysis and prediction based on GBD 2019].

Objective: Based on the data of Global Burden of Disease 2019 data, to analyze the past, current, and future burden of disability-adjusted life years (DALYs) in China and compare with the international status. Methods: The total number of DALYs, age-standardized DALY rate, and the composition of different subgroups were extracted and described to analyze the time trend in 2000-2019 and the current situation in 2019 for Chinese female breast cancer. The burden of DALYs in 2050 was predicted by Joinpoint using average annual percent change (AAPC). Results: In 2000-2019, the ranking of DALYs caused by female breast cancer in China rose from the fourth to the second in all female cancers. The total DALYs increased by 48.4%, of which the years lived with disability increased from 4.8% to 8.8%. The age-standardized DALY rate only slightly decreased (AAPC=-0.3%; which increased during 2016-2019, AAPC=1.6%). In 2019, the age-standardized DALY rate for breast cancer in China was 278.0/100 000. The DALYs were 2.88 million (accounting for 14.2% of the global burden and 12.1% of all female cancers burden in China), 26.5% of which attributed known risk factors (overweight and obesity were the largest: 0.34 million DALYs, but some common breast cancer risk factors were not available on the platform, such as menstruation and fertility). In 2050, the prediction suggests that the total DALYs caused by female breast cancer in China will reach 3.80 million person-years-5.16 million person-years, increasing 32.1%-79.4% over 2019. From 2000 to 2019, the peak age of DALYs and DALY rate became older, and the DALYs among females aged 65 years and above increased faster than those younger than 65 years (AAPC were 4.8% and 1.3%, respectively). In 2019, females aged 45-74 (the starting age recommended by local guidelines for breast cancer screening) contributed 74.3% of the total DALYs. Conclusions: Over the past 20 years, the age-standardized DALY rate for breast cancer in female populations in China has not changed obviously. Without the continuous expansion of effective intervention and population aging, the burden of DALYs for female breast cancer in China will increase. DALYs for breast cancer attributed leading risk factors were still limited.

[Gender differences in cardiovascular risk factors in patients with acute myocardial infarction in China].

Objective: To understand gender differences of cardiovascular risk factors in patients with acute myocardial infarction (AMI) in China. Methods: A total of 26 592 patients with AMI from 107 hospitals in 31 provinces in China from January 1, 2013 to September 30, 2014 were included. Self-designed questionnaire was used to collect patients' age, gender, height, weight, type of AMI, medical history of cardiovascular and cerebrovascular diseases, medication history, lifestyle and AMI risk factors, including high blood pressure, diabetes, dyslipidemia, overweight and/or obesity, smoking history and family history of early onset coronary artery disease. A total of 24 394 patients with complete clinical data were included in the analysis, and gender differences in cardiovascular risk factors were analyzed in all and subgroups with different characteristics. Results: The patients were (62.2±13.8) years old, including 18 162 (74.5%) males and 18 209 (74.6%) ST-segment elevation myocardial infarction (STEMI). The age of male patients was (60.2±13.7) years, which was younger than that of female patients [(68.2±12.3) years]. The body mass index of male patients was (24.2±3.0) kg/m2, which was higher than that of female patients [(23.8±3.4) kg/m2]. The proportions of patients with overweight and/or obesity, smoking history, dyslipidemia, family history of early onset coronary heart disease, fatty diet and history of AMI were 51.8%, 55.2%, 7.2%, 3.8%, 80.4% and 7.7%, which were higher than those of females (45.9%, 9.9%, 5.8%, 2.3%, 65.0% and 5.9%, respectively]. The proportions of hypertension, diabetes, physical inactivity and stroke history were 46.5%, 17.2%, 77.8% and 8.5%, respectively, which were lower than those in female patients [61.4% (3 829 cases), 24.8%, 81.7% and 11.1%, respectively] (all P values<0.05).The proportions of peripheral vascular diseases history in male and female patients were 0.6% and 0.7%, respectively, with no statistical significance in difference (P>0.05). Subgroup analysis showed inconsistent results comparing to analysis of all patients: there were no statistical significance in gender differences as for the proportion of dyslipidemia in the non-ST-segment elevation MI group, the proportion of family history of early onset coronary heart disease in the young and middle aged groups, the proportion of overweight and/or obesity, and the proportion of physical inactivity in the elderly group (all P values>0.05). Conclusions: There are gender differences in cardiovascular risk factors among Chinese patients with acute myocardial infarction. Hypertension and diabetes are more common in women, and overweight and/or obesity, fatty diet and smoking are more common in men.

[Disease burden of colorectal cancer in China: any changes in recent years?]

Objective: To update the disease burden of colorectal cancer (CRC) in Chinese population by integrating the latest multi-source evidences. Methods: Groups of data from GLOBOCAN, series of Chinese Cancer Registry Annual Report (annual report), Cancer Incidence in Five Continents (CI5), Global Burden of Disease Project 2017 (GBD), China Death Cause Surveillance Datasets and China Health Statistical Yearbooks (yearbook) were used to extract the information. Data on incidence, mortality, disability-adjusted life year (DALY) and percentage distribution of sub-location of CRC were used to analyze the latest disease burden in China, and age-standardized rates by world standard population were mainly used. Joinpoint Trend Analysis Software 4.7.0.0 was applied for time trend analysis. Data related to the economic burden of CRC in China were gathered by literature review. Results: (1) Current status: according to the latest annual report, the incidence and mortality rates of CRC were 17.1 per 100 000 and 7.9 per 100 000, respectively among the covered registration sites in 2015. The incidence ratios of male to female and that of urban to rural were 1.5 and 1.4, with the mortality ratios were 1.6 and 1.4, respectively. Similar to data from the annual report, the mortality rate was reported as 6.9 per 100 000 in 2017 by the surveillance data sets. Data from the GBD project showed that, the DALYs caused by CRC in China in 2017 was 4.254 million person years (doubled compared with that of 1990), accounting for 22.4% of the global burden of CRC. (2) Time trends: according to the annual reports, from 2009 to 2015, the incidence rate and mortality rate of CRC in China decreased by 10.2% and 9.5%, respectively. The same trend was also observed in urban sites, but was opposite in rural areas (increased 20.0% in incidence and 15.2% in mortality). Results from the Joinpoint analysis showed that the averaged annual percentage change (AAPC) was estimated as -1.6% (P<0.05) in the national mortality rate. Similarly, in the incidence and mortality rates of urban sites appeared as AAPC=-1.5% and -1.4% (all P<0.05), but inversely in the incidence rate from the rural sites as AAPC=3.3% (P<0.05). The yearbook data showed a 9.8% increase in urban and 20.6% increase in rural on the mortality in 2017 when compared with 2004, but the Joinpoint analysis showed no statistical significance (P<0.05). (3) Distribution of sub-location of CRC: the annual report showed that among all the new CRC cases in China in 2015, colon, rectal and anal cancer accounted for 49.6%, 49.2% and 1.2%, respectively, while the proportions were 51.3%, 47.6% and 1.1%, respectively in 2009. The proportion of colon cancer was continuously higher in the urban (>52%) than that in the rural areas (<44%). The CI5 Ⅺ data showed that ascending and sigmoid colons were more commonly seen among all the colon cancers. (4) Economic burden: the average annual growth rate of the medical expenditure per CRC patient in China ranged from 6.9% to 9.2%, and the 1-year out-of-pocket expenditure of a newly diagnosed patient accounted for about 60% of their previous-year household income. Conclusions: In China, the overall disease burden of CRC might have been decreased slightly but generally remained stable in the last several years, however, the rising burden appeared in the rural areas should not be ignored. In consistent with findings from a previous review, men and people from the urban areas are considered the target populations for CRC. The finding of higher proportion of colon cancer in urban areas suggests the impact of development of socioeconomic and medical technologies on CRC development and detection. The economic burden of CRC continued to grow.

[Disease burden of liver cancer in China: an updated and integrated analysis on multi-data source evidence].

Objective: To analyze the disease burden of liver cancer in China. Methods: Based on eight data sources, including the series of Chinese Cancer Registry Annual Report, three national death cause surveys in China, China Health Statistical Yearbook, China Death Cause Surveillance Datasets, GLOBOCAN, Cancer Incidence in Five Continents (CI5), WHO Mortality Database and the Global Burden of Disease (GBD), the information on incidence, mortality and disability-adjusted life year (DALY) of liver cancer, were extracted for the analysis on the past, current and future disease burden caused by liver cancer in China. Results: 1) Past situation: The long-term data from 1973 to 2012 reported by the CI5 showed that in urban populations in China (taking Shanghai as an example), the incidence rate of liver cancer in males and females decreased by 41.3% and 36.3%, respectively, and that in rural areas (taking Qidong as an example) decreased by 32.3% and 12.2%, respectively. The Chinese Cancer Registry Annual Reports showed that the national incidence and mortality rates of liver cancer decreased by 8.1% and 12.8% respectively from 2005 to 2015. The Joinpoint analysis based on the data from the China Health Statistics Yearbook also showed a declining trend: the average annual percentage change of liver cancer mortality in China from 2002 to 2017 was -3.0% (P<0.05), and that in rural areas was -3.1% (P<0.05). 2) Current status: GLOBOCAN estimates that the rates of incidence, mortality and prevalence of liver cancer in China in 2018 were 18.3 per 100 000, 17.1 per 100 000 and 10.8 per 100 000, respectively. According to the latest annual report, the incidence and mortality rates of liver cancer in cancer registration areas in 2015 were 17.6 per 100 000 and 15.3 per 100 000, respectively, and both increased with age. The mortality rate was similar to that reported in 2017 (16.7 per 100 000) by the China Death Cause Surveillance Datasets, and the male to female ratio of live cancer deaths was estimated as 3.1. The GBD 2017 reports that the DALYs caused by liver cancer in China reached 11 153.0 thousand in 2017 (accounting for 53.7% of the global DALYs) and hepatitis B virus infection was always the leading cause. 3) Prediction: The GLOBOCAN 2018 predicts that, by 2040, the number of liver cancer cases and deaths in China would reach 591 000 and 572 000 (with an increase of 50.5% and 54.9%, respectively, compared with those in 2018), with a more significant increase in people over 70 years old. 4) Economic burden: According to the literature review of economic burden data on liver cancer, the direct medical expenditure per patient with liver cancer generally showed a rising trend. Conclusions: Multiple data sources indicate that the incidence and mortality rates of liver cancer in populations in China decreased in the past decades, indicating the effect of population interventions. However, the population-level disease burden are still substantial, and comprehensive intervention strategies need to be continually strengthened and optimized, especially the primary and secondary prevention.

[Population's acceptance and attitude toward a novel fecal immunochemical test for colorectal cancer screening: a multi-center survey in China].

Objective: To investigate the acceptance and attitude toward a novel fecal immunochemical test (FIT) in colorectal cancer screening among populations in China. Methods: From May 2018 to May 2019, 2 474 people aged 50-74 years were recruited from five provinces of China (Zhejiang, Anhui, Jiangsu, Hunan and Yunnan). The general demographic characteristics, acceptance of the new FIT technology and operational difficulties through the whole screening process were obtained through questionnaire survey. Multivariate logistic regression model was used to analyze the factors related to difficulties encountered in sampling stool, reading and uploading results. Results: The subjects were (60.0±6.4) years old, and female, high school of above educated, unemployed/retired/other, married and with medical insurance status of "new rural cooperative medical care (NRCMC)" accounted for 61.7% (1 526), 29.0%(718), 34.3% (849), 92.7% (2 293) and 31.3%(775), respectively. The population's acceptance of the FIT technology was 94.8%. In the process of FIT screening, the percentage of occurred difficulties in sampling stool, reading and uploading results were 33.1% (819), 46.4% (1 147) and 62.9% (1 557), respectively. The main difficulties were the uncertainty about whether the sampling operation was standard (28.0%), the inability to accurately judge the result displayed (32.5%) and the need for help without using a smartphone (44.2%). The results of multivariate logistic regression model analysis showed that people aged 65-74 years old and with medical insurance status of "NRCMC" were more likely to encounter difficulties in sampling, and those who were unemployed/retired/other and living with 3 or more family members were less likely to encounter difficulties in sampling. Those aged 65-74 years old, farmers or migrant workers, and those with "NRCMC" were more likely to encounter difficulties in readingresults, and those with 3 or more family members were less likely to encounter difficulties in reading result. Those with "NRCMC" were more likely to encounter difficulties in uploading results, and those with education level of high school or above, living with more than 3 family members were less likely to encounter difficulties in uploading results. Conclusion: The acceptance of the new FIT technology is relatively high among the subjects. Age, education level, occupation, number of family members living together and medical insurance status might be related to difficulties encountered in sampling stool, reading and uploading results, and it can be further strengthened in terms of the technology and characteristics of sub-populations.

[Health economic evidence for colorectal cancer screening programs in China: an update from 2009-2018].

Objective: This study was to systematically update the economic evaluation evidence of colorectal cancer screening in mainland China. Methods: Based on a systematic review published in 2015, we expanded the scope of retrieval database (PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, CBM) and extended it to December 2018. Focusing on the evidence for nearly 10 years (2009-2018), basic characteristics and main results were extracted. Costs were discounted to 2017 using the consumer price index of medical and health care being provided to the residents, and the ratio of incremental cost-effectiveness ratio (ICER) to per capita GDP in corresponding years were calculated. Results: A total of 12 articles (8 new ones) were included, of which 9 were population-based (all cross-sectional studies) and 3 were model-based. Most of the initial screening age was 40 years (7 articles), and most of the frequency was once in a lifetime (11 articles). Technologies used for primary screening included: questionnaire assessment, immunological fecal occult blood test (iFOBT) and endoscopy. The most commonly used indicator was the cost per colorectal cancer detected, and the median (range) of the 20 screening schemes was 52 307 Chinese Yuan (12 967-3 769 801, n=20). The cost per adenoma detected was 9 220 Yuan (1 859-40 535, n=10). In 3 articles, the cost per life year saved (compared with noscreening) was mentioned and the ratio of ICER to GDP was 0.673 (-0.013-2.459, n=11), which was considered by WHO as "very cost-effective" ; The range of ratios overlapped greatly among different technologies and screening frequencies, but the initial age for screening seemed more cost-effective at the age of 50 years (0.002, -0.013-0.015, n=3), than at the 40 year-olds (0.781, 0.321-2.459, n=8). Conclusions: Results from the population-based studies showed that the cost per adenoma detected was only 1/6 of the cost per colorectal cancer detected, and limited ICER evidence suggested that screening for colorectal cancer was generally cost-effective in Chinese population. Despite the inconclusiveness of the optimal screening technology, the findings suggested that the initial screening might be more cost-effective at older age. No high-level evidence such as randomized controlled trial evaluation was found.

[Priority setting in scaled-up cancer screening in China: an systematic review of economic evaluation evidences].

Objective: The existed economic evaluations of cancer screening in Chinese population are almost all single-cancer focused, evidence on parallel comparison among multiple cancers is lacking. Thus, the aim of this study was, from a priority setting perspective, to compare the cost-effectiveness of six common cancers(colorectal cancer, breast cancer, liver cancer, lung cancer, esophageal cancer and stomach cancer) to facilitate policy making in future scaled-up screening in populations in China. Methods: Partially based on our previous single-cancer systematic reviews (colorectal cancer, breast cancer, liver cancer, and lung cancer), evidence of economic evaluations of cancer screening in populations in mainland China were systematically updated and integrated. The main updates include: 1) Stomach cancer and esophageal cancer were newly added to the current analysis. 2) The literature searching was extended to 8 literature databases, including PubMed, EMbase, The Cochrane Library, Web of Science, CBM, CNKI, Wanfang Data, and VIP. 3) The period of publication year was updated to the recent 10 years: January 1, 2009 to December 31, 2018. 4) The study focused on populations in mainland China. Following the standard processes of literature searching, inclusion and exclusion from previous systematic reviews, the basic characteristics, evaluation indicators and main results of the included studies were extracted. All the costs were discounted to 2017 value using the by-year consumer price index of medical and health care residents in China and presented in the Chinese Yuan (CNY). The ratios of incremental cost-effectiveness ratio (ICER) to China's per capita GDP in 2017 were calculated (<1 means very cost-effective, 1-3 means cost-effective, >3 means not cost-effective). Given a specific indicator, the median value among all reported screening strategies for each cancer was calculated, based on which priority ranking was then conducted among all cancers when data available. Results: A total of 45 studies were included, 22 for breast cancer, 12 for colorectal cancer, 6 for stomach cancer, 4 for esophageal cancer (all conducted in high-risk areas), 1 for liver cancer and none for lung cancer (was not then considered for next ranking due to limited numbers of studies). When based on the indicator, the median ratio of cost per life-year saved to China's per capita GDP (reported in 12 studies), the lowest ratio (-0.015) was observed in esophageal cancer among 16 strategies of 2 studies (N=2, n=16), followed by 0.297 for colorectal cancer (N=3, n=12), 0.356 for stomach cancer (N=1, n=4) and 0.896 for breast cancer (N=6, n=52, P(75)=3.602). When based on another commonly used ICER indicator, the median ratio of cost per quality-adjusted life-year gained to China's per capita GDP (reported in 13 studies), the least cost was found in stomach cancer (0.495, N=3, n=8, P(75)=3.126), followed by esophageal cancer (0.960, N=1, n=4, P(75)=1.762) and breast cancer (2.056, N=9, n=64, P(75)=4.217). Data was not found for colorectal cancer. In addition, cost per cancer case detected was the most adopted indicator (32 studies). The median cost among all screening strategies for each cancer was 14 759 CNY for stomach cancer (N=5, n=7), 49 680 CNY for colorectal cancer (N=12, n=25) and 171 930 CNY for breast cancer (N=13, n=24), respectively. Data was not available for esophageal cancer and rare for precancer cases detected. Evidence related to cost per disability-adjusted life-year gained was not available. Conclusions: At China's national level and limited to the six cancers covered by the current study, the preliminary analysis suggests that stomach cancer and colorectal cancer were the most cost-effective target cancers and could be given priority in the future scaled-up screening in general populations. Esophageal cancer screening should be prioritized in high-risk areas. Breast cancer was also cost-effective in general but some of the intensive screening strategies were marginal. Data on liver cancer and lung cancer were too limited to conclude, and more well-designed studies and high-quality research evidence should be required. This priority ranking might be changed if other common cancers were involved analyses.

[B7-H3 silencing inhibits human hematological malignancy xenograft tumor tumorigenesis and metastasis in nude mice].

OBJECTIVE: To investigate the effect and mechanism of targeted B7-H3 gene silencing on the tumorigenesis and metastasis of human hematological malignancy xenograft tumor in nude mice. METHODS: Real-time fluorogentic quantitative PCR (qPCR) and flow cytometry (FCM) were used to detect the expression of B7-H3 in 13 strains of malignant hematologic cells. Then, U937, Maver and Z138 cells which expressed high level of B7-H3 were screened out. Targeted B7-H3 knockdown in U937, Maver and Z138 was performed by lentivirus transduction and the effect of B7-H3 silencing in stable cell lines was tested by qPCR and FCM. Injecting the nine groups subcutaneously into the nude mice to establish xenograft models after dividing the U937, Maver and Z138 into non-infected control group (CON), B7-H3 knockdown group (KD) and negative non-targeted control infected group (NC),respectively, for detecting the tumorigenicity and metastasis in vivo. Furthermore, the expression of Ki-67 in xenograft tumors was detected by immunohistochemistry (IHC). The expression of metalloproteinase 2 (MMP-2) was detected by western blot. RESULTS: The stable B7-H3 silencing cell lines of U937, Maver and Z138 were successfully established. Compared with the NC group, the KD groups of U937, Maver and Z138 had an obviously slower tumor growth. The average tumor inhibition rates at the end of observation period were 61.83% (F=43.78, P<0.05), 59.12% (F=36.51, P<0.05) and 67.37% (F=40.29, P<0.05); there was no significant difference in tumor volume growth between the NC group and the CON group (P>0.05). The liver distant metastasis of all the xenograft tumor models in nude mice was the most common and the rates of distant metastasis in KD groups were significantly lower than that of the corresponding NC groups. The Ki-67 indexes of the KD groups were significantly lower than those of the relative NC groups in three cell lines (U937: 40.3%±5.2% vs. 79.1%±6.3%, q=30.31, P<0.05, Maver: 35.2%±6.4% vs. 69.6%±5.1%, q=24.82, P<0.05; Z138: 38.4%±7.1% vs. 75.7%±4.8%, q=28.07, P<0.05); there was no significant difference in the expression of Ki-67 between the NC group and the CON group (P>0.05). The expressions of MMP-2 were also significantly lower in the KD groups than in the NC groups (U937: q=14.59, P<0.05; Maver: q=9.25, P<0.05; Z138: q=11.04, P<0.05); there was no significant difference in the expression of MMP-2 between the NC group and the CON group (P>0.05). CONCLUSION: Targeted B7-H3 gene silencing could inhibit the tumorigenesis and metastasis of human hematological malignancy xenograft tumor in nude mice. The mechanism may be related to the down-regulation of Ki-67 and MMP-2.

Functional polymorphisms of the cyclooxygenase-2 gene and prognosis of hepatocellular carcinoma - a cohort study in Chinese people.

Cyclooxygenase-2 (COX-2) influences carcinogenesis through regulation of angiogenesis, apoptosis, cytokine expression, and immune response suppression. It has been well established that COX-2 is overexpressed in a variety of human cancers, such as hepatocellular carcinoma (HCC). In this study, we aimed to evaluate the association between COX-2 polymorphisms and prognosis of HCC. We genotyped 200 HCC patients of Chinese Han descent for COX-2 gene polymorphisms (-765G>C and -1195G>A) using PCR-RFLP. Data were statistically analyzed using the Kaplan-Meier method and the Cox's proportional hazard regression model. We found that patients with the COX-2 -1195AG and -1195AG + AA genotypes demonstrated significantly decreased disease-free survival (DFS) as compared with those carrying the -1195GG genotype (P < 0.05). However, the COX-2 -765G>C polymorphism was not associated with DFS (P > 0.05). Moreover, by Cox regression analysis, blood alpha fetoprotein ≤400 ng/mL before the operation and the -1195G>A polymorphism were found to be of prognostic significance (P < 0.05), while the -765G>C polymorphism was not (P > 0.05). In summary, post-operation progression of HCC is more likely to occur in patients with the -1195AG genotype and the A allele. On the other hand, the -765G>C polymorphism is not an independent influence factor of HCC prognosis.

CARD9 mutation linked to Corynespora cassiicola infection in a Chinese patient.

Corynespora cassiicola is a plant pathogen associated with leaf-spotting disease. The fungus has been found on diverse substrates: leaves, stems and roots of plants; nematode cysts and human skin. It rarely causes human infections. Here we report one case of subcutaneous phaeohyphomycosis caused by C. cassiicola with prominent tissue necrosis in a woman. All of her clinical features pointed towards a genetic linkage. Hence, whole-exome sequencing and Sanger sequencing were performed on this patient. One mutation of CARD9 was detected.

Olfactory experience modulates immature neuron development in postnatal and adult guinea pig piriform cortex.

Immature neurons expressing doublecortin (DCX+) are present around cortical layer II in various mammals including guinea pigs and humans, especially enriched in the paleocortex. However, little is known whether and how functional experience affects the development of this population of neurons. We attempted to explore a modulation by experience to layer II DCX+ cells in the primary olfactory cortex in postnatal and adult guinea pigs. Neonatal and 1-year-old guinea pigs were subjected to unilateral naris-occlusion, followed 1 and 2months later by morphometry of DCX+ cells in the piriform cortex. DCX+ somata and processes were reduced in the deprived relative to the non-deprived piriform cortex in both age groups at the two surviving time points. The number of DCX+ cells was decreased in the deprived side relative to internal control at 1 and 2months in the youths and at 2months in the adults post-occlusion. The mean somal area of DCX+ cells showed a trend of decrease in the deprived side relative to the internal control in the youths. In addition, DCX+ cells in the deprived side exhibited a lower frequency of colocalization with the neuron-specific nuclear antigen (NeuN) relative to counterparts. These results suggest that normal olfactory experience is required for the maintenance and development of DCX+ immature neurons in postnatal and adult guinea pig piriform cortex.

An age-related axon terminal pathology around the first olfactory relay that involves amyloidogenic protein overexpression without plaque formation.

The glomeruli are the first synaptic relay on the olfactory pathway and play a basic role in smell perception. Glomerular degeneration occurs in humans with age and in Alzheimer's disease (AD). The glomeruli heavily express ß-amyloid precursor protein (APP), ß-secretase (BACE1) and γ-secretase complex. However, extracellular ß-amyloid peptide (Aß) deposition occurs fairly rarely at this location in postmortem pathological studies. We sought to explore age-related glomerular changes that might link to alteration in amyloidogenic proteins and/or plaque pathogenesis in transgenic models of AD and humans. Focally increased BACE1 immunoreactivity (IR) in the glomerular layer was identified in several transgenic models, and characterized systematically in transgenic mice harboring five familiar AD-related mutations (5XFAD). These elements were co-labeled with antibodies against APP N-terminal (22C11) and Aß N-terminal (3D6, 6E10) and mid-sequence (4G8). They were not co-labeled with two Aß C-terminal antibodies (Ter40, Ter42), nor associated with extracellular amyloidosis. These profiles were further characterized to be most likely abnormal olfactory nerve terminals. Reduced glomerular area was detected in 6-12-month-old 5XFAD mice relative to non-transgenic controls, and in aged humans relative to young/adult controls, more robust in AD than aged subjects without cerebral amyloid and tau pathologies. The results suggest that olfactory nerve terminals may undergo age-related dystrophic and degenerative changes in AD model mice and humans, which are associated with increased labeling for amyloidogenic proteins but not local extracellular Aß deposition. The identified axon terminal pathology might affect neuronal signal transmission and integration at the first olfactory synaptic relay.

Identification of two novel splice mutations of the ADAR1 gene in two Chinese families with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is a rare, autosomal dominant dermatosis, characterized by a mixture of hyperpigmented and hypopigmented macules on the dorsa of the hands and feet. The DSH locus has been mapped to chromosome 1q21, and in 2003, pathogenic mutations were identified in the ADAR1 (adenosine deaminase acting on RNA1) gene. In this study, we performed mutation detection of the ADAR1 gene in two Chinese families with DSH. PCR and direct sequencing of the ADAR1 gene were used to identify and confirm the mutations in the two families. Furthermore, we analysed the RNA transcripts by reverse transcriptase (RT)-PCR. Two aberrant splice products were confirmed with RT-PCR and DNA direct sequence analysis. These novel findings further extend our understanding of the role of ADAR1 in DSH.

Alteration of GABA transporter expression in the rat cerebral cortex following needle puncture and colchicine injection.

In the adult cerebral cortex, GABA transporters (GATs) are expressed by both neurons and astrocytes. GAT-1 immunoreactivity is found in axon terminals of GABAergic neurons and astrocytes, while GAT-3 immunolabeling occurs only in the latter. The present study was designed to determine whether the expression of GAT-1 and GAT-3 in the adult rat cerebrum changes after needle lesion and colchicine infusion. Following a needle puncture or a saline injection, immunolabeling for GAT-1 and GAT-3 was slightly increased in an area around the needle track. Not only was the neuropil labeling for both GATs increased, but also a few neuronal somata were found to be immunoreactive for GAT-1. Colchicine injections induced a striking increase in immunolabeling for both GATs in the neuropil in an area adjacent to the needle path and surrounding it. A homologous region of the contralateral hemisphere also showed a moderate increase of immunoreactivity in the neuropil for both GATs. Furthermore, this contralateral site showed many neuronal somata immunolabeled for GAT-1. These changes were mainly detected during the first 5 days following intracortical lesions. These results indicate that (1) the upregulation of GAT-1 and GAT-3 in cortical interneurons and astrocytes is caused by both mechanical and chemical factors associated with the injections; (2) increased GAT-1 and GAT-3 expression contralateral to the site of colchicine injection is mediated by transcellular signaling across the corpus callosum; and (3) the lesion-induced GAT expression may play a protective role by helping to balance excitatory and inhibitory neuronal activities.

Developmental expression of gamma-aminobutyric acid transporters (GAT-1 and GAT-3) in the rat cerebellum: evidence for a transient presence of GAT-1 in Purkinje cells.

The cerebellar cortex contains several classes of GABAergic neurons. Previous studies have shown that most GABAergic neurons in this region possess the capacity for gamma-aminobutyric acid (GABA) uptake. The present study determined the postnatal expression of two GABA transporters, GAT-1 and GAT-3, in the cerebellar cortex and deep nuclei of the rat by using immunocytochemistry. Immunoreactivity for GAT-1 and GAT-3 appears at postnatal day 7 (P7), emerges centroperipherally across the cerebellum during the following 2 weeks and reaches an adult-like pattern by P30. The mature patterns are fully established by P45, which for GAT-1 is characterized by immunolabeled profiles localized exclusively to neuropil, mostly in the molecular layer and the pinceaux deep to the Purkinje cell bodies, and for GAT-3 as immunoreactivity distributed in the neuropil of mainly the granular layer. Before the adult patterns are completed, GAT-1 immunoreactivity is present in the somata of Purkinje, Golgi, basket and stellate cells between P7 and P21, while GAT-3 immunoreactivity is distinct in astrocytic somata which are organized in regularly spaced clusters. During this period, there is also a banding pattern in the sagittal plane of GAT-1 immunoreactivity in developing Purkinje cells. The postnatal development of GAT-1 and GAT-3 in the rat cerebellar cortex shares a similar spatiotemporal pattern with other GABAergic parameters, including the GABA synthesizing enzyme, GABA content and uptake. Specifically, the transient expression of GAT-1 in the somata and dendrites of cerebellar GABAergic neurons appears to correlate with the supra-adult levels of whole-tissue GABA uptake capability during development. Further, GAT-1 expression in immature Purkinje cells may play a unique role in regulating GABA's function during development, since mature Purkinje cells do not express GAT-1 or take up GABA.

Increased expression of GABA transporters, GAT-1 and GAT-3, in the deafferented superior colliculus of the rat.

GABA transporters (GATs) play a critical role in the translemmal transport of GABA in neurons and glial cells. Two major brain GATs, GAT-1 and GAT-3, are found in astrocytes in the adult brain. Astroglia demonstrate morphological and molecular changes in response to brain injury and deafferentation. The present study was designed to determine whether the expression of GATs changes after nerve deafferentation using the rat superior colliculus (SC) as a model. The immunoreactivity for GAT-1 and GAT-3, as well as GABA and glutamic acid decarboxylase (GAD)-65 and GAD-67, was studied in the SC of control rats and rats with unilateral optic nerve transections. Immunolabeling for both GAT-1 and GAT-3 was increased in the neuropil of the denervated SC as compared to that for the SC of control rats or for the unaffected SC of experimental rats. In contrast, immunoreactivity for GABA, GAD-65 and GAD-67 was not altered. The change in the immunolabeling of GAT-1 and GAT-3 was detectable at 1 day postlesion and became more evident between 3-30 days postlesion. At the electron microscopic level, immunoreactivity for both GAT-1 and GAT-3 in the unaffected SC was localized to astrocytic processes, whereas GAT-1 immunolabeling was also present in synaptic terminals. In the deafferented SC, immunolabeling for both GATs was elevated in the somata and processes of hypertrophied astrocytes as compared to that in the unaffected SC, whereas GAT-1 labeling in neuronal profiles was largely unchanged. A substantial increase of GAT-1 and GAT-3 in astrocytes following optic nerve transection suggests that these cells play a role in modulating GABA's action in the deafferented SC.