[Current status and treatment strategies for liver injury before targeted immunotherapy for liver cancer].

The occurrence rate of primary liver cancer in malignant tumors ranks sixth in the world, and the mortality rate ranks third, with a poor prognosis and a five-year survival rate of less than 5%. Most patients with liver cancer in China are found to be in the intermediate and advanced stages, and a targeted immunotherapy combination has become the main treatment option. However, many patients have underlying liver lesions, and their liver function cannot meet the requirements of targeted immunotherapy, which directly affects the treatment of liver cancer patients. Therefore, it is very important to optimize the patient's liver function in a timely manner so as to obtain the opportunity for anti-tumor therapy. This article reviews the current status and response strategies before liver injury related to targeted immune therapy in patients with primary liver cancer.

[Preclinical evaluation of a veno-venous bypass device for liver transplantation based on the principle of magnetic levitation drive].

Objective: To explore the performance of a self-made venous-venous bypass (VVB) device for liver transplantation based on the principle of magnetic levitation drive. Methods: Experimental study was conducted from August 2020 to January 2022. Eight Bama minipigs underwent VVB of hepatic portal vein-femoral vein-internal jugular vein after occlusion of hepatic portal vein and inferior vena cava. The animals were divided into two groups according to the VVB devices used during VVB. A self-made VVB device was used in group A(n=5),and an imported VVB device was used in group B(n=3). The hemodynamic changes of the two groups of animals were compared at 6 time points including before vascular occlusion, during vascular occlusion, 30 minutes, 60 minutes, 90 minutes after the start of VVB, and 30 minutes after vascular opening. In addition,the changes of blood compatibility indexes,intestinal injury indexes,kidney injury indexes and internal environment indexes of the two groups of animals at each time point were compared. The independent samples t test was used for the quantitative data between the two groups with non-repeated measures,and the repeated measures analysis of variance was used for the quantitative data between the two groups with repeated measures. Results: During the VVB of the two devices,the venous drainage was sufficient,and the main manifestations were that the color of the intestine of the Bama miniature pig was ruddy, the peristalsis was normal, and the urine output was normal. There were no significant differences in hemodynamics,blood injure indexes,intestinal injury indexes,kidney injury indexes,neutropil gelatinase-associated lipocalin,and internal environment indexes(all P>0.05).The indexes at 30 minutes after vascular opening in the group A and the group B were as follows:mean arterial pressure were (71.0±7.7)mmHg(1 mmHg=0.133 kPa) and (74.0±8.7)mmHg,central venous pressure were (7.0±1.4)cmH2O(1 cmH2O=0.098 kPa) and (7.7±0.6)cmH2O,heart rate were (131±10) beats/minutes and (132±8)beats/minutes; red blood cell count were (6.43±0.89)×1012/L and (6.32±0.58)×1012/L,hemoglobin were (108.4±5.9)g/L and (110.0±3.5)g/L,free hemoglobin were (78.28±3.96)mg/L and (78.08±4.54)mg/L; intestinal fatty acid binding protein were (2.27±0.49)µg/L and (2.40±0.78)µg/L;creatinine were (68.30±9.77)µmol/L and (79.90±26.91)µmol/L,blood urea nitrogen were (3.94±1.39)mmol/L and (3.45±0.65)mmol/L;neutropil gelatinase-associated lipocalin were (4.02±0.53) µg/L and (3.86±0.23)µg/L;pH value were 7.27±0.04 and 7.23±0.03,lactic acid were (6.18±2.62)mmol/L and (4.30±0.50)mmol/L,concentrations of Na+ were (136.3±3.0)mmol/L and (137.6±1.6) mmol/L,concentrations of K+ were (3.89±0.42) mmol/L and (3.98±0.17)mmol/L,concentrations of Ca2+ were (1.40±0.03)mmol/L and(1.40±0.04)mmol/L;all indexes in the two group had no differences(all P>0.05). Conclusion: The self-made venous bypass device can be safely and effectively applied to VVB of Bama minipigs,and achieves the same performance as the imported venous bypass device.

[China guideline for the screening, early detection and early treatment of gastric cancer (2022, Beijing)].

Gastric cancer (GC) is a major digestive tract malignancy in China, which seriously threatens the health of Chinese population. A large number of researches have demons-trated that screening, early detection and early treatment are effective in reducing the incidence and mortality of GC. The development of the guideline for GC screening, early detection and early treatment in line with epidemic characteristics of GC in China will greatly promote the homogeneity and standardization, and improve the effect of GC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. Following the World Health Organization Handbook for Guideline Development, this guideline combined the most up-to-date evidence of GC screening, China's national conditions, and practical experience in cancer screening. This guideline provided evidence-based recommendations with respect to the screening population, technology and procedure management, aiming to improve the effect of GC screening and provide scientific evidence for the GC prevention and control in China.

[China guideline for the screening, early detection and early treatment of esophageal cancer (2022, Beijing)].

Esophageal cancer (EC) is a major digestive tract malignancy in China, which seriously threatens the health of Chinese population. A large number of researches have demonstrated that screening and early detection are effective in reducing the incidence and mortality of EC. The development of the guideline for EC screening and early detection in line with epidemic characteristics of EC in China will greatly promote the homogeneity and standardization, and improve the effect of EC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. Following the World Health Organization Handbook for Guideline Development, this guideline combined the most up-to-date evidence of EC screening, China's national conditions, and practical experience in cancer screening. This guideline provided evidence-based recommendations with respect to the screening population, technology and procedure management, aiming to improve the effect of EC screening and provide scientific evidence for the EC prevention and control in China.

[Analysis of low-dose computed tomography compliance and related factors among high-risk population of lung cancer in three provinces participating in the cancer screening program in urban China].

Objective: To analyze the compliance and related factors of low-dose computed tomography (LDCT) screening among the high-risk population of lung cancer in three provinces participating in the cancer early diagnosis and early treatment program in urban areas of China. Methods: From October 2017 to October 2018, 17 983 people aged between 40 and 74 years old at high risk of lung cancer were recruited from Zhejiang, Anhui and Liaoning provinces. The basic demographic characteristics, living habits, history of the disease and family history of cancer were collected by using a cancer risk assessment questionnaire, and the data of participants examined by LDCT were obtained from the hospitals participating in the program. The screening compliance was quantified by the screening participation rate, and it was calculated as the proportion of participants completing LDCT scan among high-risk population. The related factors of LDCT screening compliance were analyzed by using a multivariate logistic regression model. Results: The age of 17 983 participants was (56.52±8.22) years old. Males accounted for 51.9% (N=9 332), and 69.5% (N=12 495) had ever smoked, including former smokers and current smokers. A total of 6 269 participants were screened by LDCT, and the screening participation rate was 34.86%. The results of multivariate logistic regression analysis showed that the age group of 50 to 69 years old, female, passive smokers, alcohol consumption, family history of lung cancer and history of chronic respiratory diseases were more likely to be screened by LDCT, while the compliance of LDCT screening in current smokers was low. Conclusions: The LDCT screening compliance of the high-risk population of lung cancer in urban areas of China still needs to be improved. Age, sex, smoking, drinking, family history of lung cancer and history of chronic respiratory disease are associated with screening compliance.

[Diagnostic performance of quantitative fecal immunochemical test in detection of advanced colorectal neoplasia].

Objective: To evaluate the diagnostic performance of quantitative fecal immunochemical testing (FIT) and to provide reference for designing effective colorectal cancer (CRC) screening strategy in China. Methods: Based on an ongoing randomized controlled trial comparing the colorectal cancer screening strategies, this current study involved 3 407 participants aged 50-74 years who had undergone colonoscopies. All the feces samples were collected from the participants prior to receiving the colonoscopy. Fecal hemoglobin (Hb) was tested by FIT following a standardized operation process. Diagnosis-related indicators of FIT were calculated using the colonoscopy results as the gold standard. Results: Among the 3 407 participants, the mean age (SD) as 60.5 (6.3) years and 1 753 (51.5%) were males. The participants involved 28 (0.8%) CRCs, 255 (7.5%) advanced adenomas, 677 (19.9%) nonadvanced adenomas, and 2 447 (71.8%) benign or negative findings. With an overall positivity rate of 2.8% (96/3 407) at the recommended cutoff value of 20 µg Hb/g, the sensitivities of FIT for both CRC and advanced adenoma were 57.1% (95%CI: 37.2%-75.5%) and 11.0% (95%CI: 7.4%-15.5%), respectively, with the corresponding specificity as 98.4% (95%CI: 97.8%-98.8%). At a decreased cut-off value of 5 µg Hb/g, the sensitivities for detecting CRC and advanced adenoma increased to 64.3% (95%CI: 44.1%-81.4%) and 16.5% (95%CI: 12.1%-21.6%), respectively, but the specificity reduced to 95.2% (95%CI: 94.4%-95.9%). The areas under the ROC curve for CRC and advanced adenoma were 0.908 (95%CI: 0.842-0.973) and 0.657 (95%CI: 0.621-0.692), respectively. Of the diagnostic performance, there were no significant differences noticed by different sex and age groups. Conclusions: In our study, the quantitative FIT showed modest sensitivity in detecting CRC but limited sensitivity in detecting advanced adenoma. In population-based CRC screening programs, the quantitative FIT had the advantage of adjusting the positive threshold based on the targeted detection rate and available resource load of colonoscopy.

[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.

[Rates on the acceptance of colonoscopy, fecal immunochemical test and a novel risk-adapted screening approach in the screening programs of colorectal cancer as well as related associated factors].

Objective: To compare the rates of acceptance of colonoscopy, fecal immunochemical test (FIT), or a novel risk-adapted screening approach in the colorectal cancer (CRC) screening program. Related risk factors were also studied. Methods: The study has been based on an ongoing randomized controlled trial on colorectal cancer screening programs in six centers of research since May 2018. The involved participants were those who presented at the baseline screening phase. All the participants were randomly allocated into one of the following three intervention arms in a 1∶2∶2 ratio: colonoscopy group, FIT group, and a novel risk-adapted screening group. All the participants underwent risk assessment on CRC by an established risk score system. The subjects with high-risk were recommended to undertake the colonoscopy while the low-risk ones were receiving the FIT. Detailed epidemiological data was collected through questionnaires and clinical examinations. Rates of participation and compliance in all three groups were calculated. Multivariate logistic regression models were used to explore the potential associated factors related to the acceptance of screening. Results: There were 19 546 eligible participants involved in the study, including 3 916 in the colonoscopy group, 7 854 in the FIT group, and 7 776 in the novel risk-adapted screening group, respectively. Among the 19 546 participants, the mean age was 60.5 years (SD=6.5), and 8 154 (41.7%) were males. The rates of participation in the colonoscopy, FIT and the novel risk-adapted screening groups were 42.5%, 94.0% and 85.2%, respectively. In the novel risk-adapted screening group, the participation rate was 49.2% for the high-risk participants who need to undertake colonoscopy and was 94.0% for the low-risk ones who need to undertake FIT. Results from the multivariate logistic regression models demonstrated that there were several factors associated with the rates of participation in CRC screening, including age, background of education, history of smoking cigarettes, previous history of bowel examination, chronic inflammatory bowel disease and family history of CRC among the 1(st)-degree relatives. Conclusions: FIT and the novel risk-adapted screening approach showed superior participation rates to the colonoscopy. Further efforts including health promotion campaign for specific target population are needed to improve the engagement which ensures the effectiveness of CRC screening programs.

[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.

[Exploratory research on developing lung cancer risk prediction model in female non-smokers].

Objective: To develop a lung cancer risk prediction model for female non-smokers. Methods: Based on the Kailuan prospective dynamic cohort (2006.05-2015.12), a nested case-control study was conducted. Participants diagnosed with primary pathologically confirmed lung cancer during follow-up were identified as the case group, and others were identified as the control group. A total of 24 701 subjects were included in the study, including 86 lung cancer cases and 24 615 control population, respectively. Questionnaires, physical examinations, and laboratory tests were conducted to collect relevant information. Multivariable-adjusted logistic regressions were conducted to develop a lung cancer risk prediction model. Area Under the Curve (AUC) and Hosmer-Lemeshow tests were used to evaluate discrimination and calibration, respectively. Ten-fold cross-validation was used for internal validation. Results: Two sets of models were developed: the simple model (including age and monthly income) and the metabolic index model [including age, monthly income, fasting blood glucose (FBG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C)].The AUC (95%CI) [0.745 (0.719-0.771)] of the metabolic index model was higher than that of the simple prediction model [0.688 (0.660-0.716)] (P=0.004). Both the simple model (PHL=0.287) and the metabolic index model (PHL=0.134) were well-calibrated. The results of ten-fold cross-validation indicated sufficient stability, with an average AUC of 0.699 and a standard error (SD) of 0.010. Conclusion: By incorporating metabolic markers, accurate and reliable lung cancer risk prediction model for female non smokers could be developed.

[Metabolic syndrome components and renal cell cancer risk in Chinese males: a population-based prospective study].

Objective: To investigate the association between metabolic syndrome (MS) components and renal cell cancer in Chinese males. Methods: All male employees and retirees of the Kailuan Group were recruited in the Chinese Kailuan Male Cohort Study. They had been experienced routine physical examinations ever two years since May 2006. A total of 104 274 males were prospectively observed by 31 December 2015. Information on demographics, height, weight, blood glucose, blood lipid, blood pressure, as well as the information of incident renal cell cancer cases were collected at the baseline investigation by questionnaire, physical measurement and laboratory test. Cox proportional hazards regression models were used to evaluate the association between baseline MS and MS components (body mass index, blood glucose, blood lipid, blood pressure) and the risk of renal cell cancer in males. Results: A total of 104 274 males were recruited in our study with a age of (51.21±13.46) years, with 823 892.96 person-years follow-up and the median follow-up time was 8.88 years. A total of 131 new renal cell cancer cases were identified in the Kailuan male cohort study, and the crude incidence density was 15.90 per 100,000 person-years. Compared with no MS, the hazard ratios (HR) (95% CI) of MS was 1.97 (1.32-2.94).When compared with normal level, the HR (95%CI) of obesity or overweight, hypertension, and dyslipidemia was 1.49 (1.04-2.14), 1.56 (1.06-2.29), and 1.77(1.23-2.54), after adjusting for potential confounding factors (i.e., age, education, income, smoke, and alcohol drink), respectively. In addition, a statistically significant trend (P for trend<0.001) of increased renal cell cancer risk with an increasing number of abnormal MS components was observed. Conclusion: Obesity or overweight, hypertension, dyslipidemia and MS may increase the risk of renal cell cancer for Chinese males.

[Total cholesterol and the risk of primary liver cancer in Chinese males: a prospective cohort study].

Objective: To investigate the association between total cholesterol (TC) and primary liver cancer in Chinese males. Methods: Since May 2006, all the male workers, including the employees and the retirees in Kailuan Group were recruited in the Kailuan male dynamic cohort study. Information about demographics, medical history and TC levels was collected at the baseline interview, as well as information on newly-diagnosed primary liver cancer cases during the follow-up period. A total of 110 612 males were recruited in the cohort by 31 December 2015. TC levels were divided into four categories by quartile (<4.27, 4.27-4.90, 4.90-5.56 and ≥5.56 mmol/L), with the first quartile group serving as the referent category. Cox proportional hazards regression model was used to evaluate the association between TC levels and primary liver cancer risk. Results: By December 31, 2015, a follow-up of 861 711.45 person-years was made with a median follow-up period of 8.83 years. During the follow-up, 355 primary liver cancer cases were identified. Compared with the first quartile, the HR of incident primary liver cancer among participants with the second, third and highest quartile TC levels were 0.76 (95%CI: 0.58-1.01), 0.59 (95%CI: 0.43-0.79), and 0.36 (95%CI: 0.25-0.52), respectively after adjusting for age, educational level, income level, smoking status, drinking status, body mass index, and HBsAg status (Pfor trend<0.001). Subgroup analyses found that the association between TC levels and primary liver cancer was robust (all Pfor trend<0.05). The results didn't change significantly after exclusion of newly-diagnosed cases within the first 2 years, males with history of cirrhosis or subjects who took antihyperlipidemic drugs, participants with higher TC levels had a lower risk of primary liver cancer (all Pfor trend<0.05) and HR(95%CI) of incident primary liver cancer among participants with the highest quartile TC levels were 0.41 (0.28-0.61), 0.36 (0.25-0.53) and 0.38 (0.26-0.54), respectively. Conslusion: In this large prospective study, we found that baseline TC levels were inversely associated with primary liver cancer risk, and low TC level might increase the risk of primary liver cancer.

[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.

[The development and validation of risk prediction model for lung cancer: a systematic review].

Objective: To systematically understand the global research progress in the construction and validation of lung cancer risk prediction models. Methods: "lung neoplasms" , "lung cancer" , "lung carcinoma" , "lung tumor" , "risk" , "malignancy" , "carcinogenesis" , "prediction" , "assessment" , "model" , "tool" , "score" , "paradigm" , and "algorithm" were used as search keywords. Original articles were systematically searched from Chinese databases (CNKI, and Wanfang) and English databases (PubMed, Embase, Cochrane, and Web of Science) published prior to December 2018. The language of studies was restricted to Chinese and English. The inclusion criteria were human oriented studies with complete information for model development, validation and evaluation. The exclusion criteria were informal publications such as conference abstracts, Chinese dissertation papers, and research materials such as reviews, letters, and news reports. A total of 33 papers involving 27 models were included. The population characteristics of all included studies, study design, predicting factors and the performance of models were analyzed and compared. Results: Among 27 models, the number of American-based, European-based and Asian-based model studies was 12, 6 and 9, respectively. In addition, there were 6 Chinese-based model studies. According to the factors fitted into the models, these studies could be divided into traditional epidemiological models (11 studies), clinical index models (6 studies), and genetic index models (10 studies). 15 models were not validated after construction or were cross-validated only in the internal population, and the extrapolation effect of models was not effectively evaluated; 8 models were validated in single external population; only 4 models were verified in multiple external populations (3-7); the area under the curve (AUC) of models ranged from 0.57 to 0.90. Conclusion: Research on risk prediction models for lung cancer is in development stage. In addition to the lack of external validation of existing models, the exploration of potential clinical indicators was also limited.

[Compound matrine injection reduces morphine tolerance of the mice with lung cancer by inhibiting expression of multidrug resistance gene 1 and P-glycoprotein].

Objective: To investigate the effect of compound matrine injection on morphine tolerance in mice with lung cancer in situ and the expressions of multidrug resistance gene 1 (MDR1) and P-glycoprotein (P-gp). Methods: A mouse model of lung cancer in situ and morphine tolerance mode was established. The mice were injected with gradient concentration of compound matrine. The pain thresholds under different conditions were measured by thermal radiation tail-flick method. The mRNA level of MDR1 was tested by reverse transcription polymerase chain reaction (RT-PCR) and the protein level of P-gp was detected by western blot. The DNA binding activity of cyclophosphoadenosine response element binding protein (CREB) to the promoter of MDR1 gene was detected by electrophoretic mobility shift assay (EMSA). Results: The maximum analgesic percentage (MPE) of the mice in the morphine group was (85.21±6.53)% on the 8th day, and decreased to (38.45±5.52)% and (28.14±4.52)% on the 10th and 12th day, respectively, which indicated the morphine tolerance of mice with lung cancer in situ.The MPE of the mice in the group treated with morphine and compound matrine injection (300 mg/kg) was (79.34±6.50)% on the 8th day, and decreased to (62.16±5.53)% and (40.20±4.50)% on the 10th and 12th day, respectively.The results of RT-PCR assay showed that the relative expression levels of MDR1 mRNA in the brain tissues of mice in the morphine group, saline group, morphine combined with compound matrine injection (300 mg/kg) group and compound matrine injection (200 mg/kg) group were 2.33±0.79, 1.04±0.38, 1.37±0.38, and 1.43±0.53, respectively. There were statistically significant differences between the morphine group and the normal saline group, the morphine group and the morphine combined with compound matrine injection (300 mg/kg) group (P<0.05). There was no significant difference between the normal saline group and the compound matrine injection (200 mg/kg) group (P=0.05). The results of western blot showed that the relative expression levels of P-gp protein in the brain tissue of mice in the morphine group, saline group, and morphine combined with compound matrine injection (300 mg/kg) group were 1.86±0.40, 1.00±0.23, and 1.27±0.27, respectively. The expression of P-gp protein in the morphine group was significantly higher than those of the normal saline group and the morphine combined with compound matrine injection (300 mg/kg) group (P<0.05). The DNA-binding activity of CREB in the saline group was (0.23±0.07) Pu, significantly lower than (0.89±0.23) Pu of morphine combined with naloxone group and (0.80±0.23) Pu of morphine group (P<0.05). While the CREB DNA binding activity of morphine combined with compound matrine injection (300 mg/kg) group was (0.79±0.21) Pu, implicated that compound matrine had marginal effect on the DNA-binding activity of CREB (P>0.05). Conclusion: Compound matrine injection can significantly improve morphine tolerance and drug resistance of lung cancer through inhibiting the upregulations of MDR1 and P-gp induced by morphine.

[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.

[Systematic review of methodological quality and reporting quality in gastric cancer screening guidelines].

Objective: To systematically evaluate the quality of gastric cancer screening guidelines/recommendations, and provide a reference for the update of gastric cancer screening guidelines/recommendations in China. Methods: "guidelines/consensus/specifications/standards" , "stomach/gastric tumors" , "screening/diagnosis" , "guideline/recommendation" , "gastric cancer/gastric tumor," "early detection of cancer/screening" were searched as keywords in PubMed, Embase, Web of knowledge, China Knowledge Network, Wanfang, China Biomedical Literature Database, and Cochrane Library, as well as the US Preventive Services Working Group, the American Cancer Society, the International Agency for Research on Cancer, the Australia Cancer Council and the International Guide Collaboration Network at the end of July 2018. The inclusion criteria were independent guidelines/recommendation documents for gastric cancer screening. The exclusion criteria were guideline abstracts, interpretation and evaluation literature, duplicate publications, updated original guidelines, and clinical treatment or practice guidelines for gastric cancer. The language was limited to Chinese and English. The European Guide to Research and Evaluation Tools (AGREE Ⅱ) and Practice Guideline Reporting Standard (RIGHT) for Gastric Cancer Screening Guidelines/Recommendations were used to compare and evaluate the quality and reporting standard of gastric cancer screening guidelines/recommendations. Results: A total of five guides/recommendations were included. The results of the AGREE Ⅱ quality evaluation showed that the overall quality of five guides/recommendations was different, including one recommended for "A", one for "B", and three for "C". Each guide/recommendation scored higher in the scope and purpose, clarity, and scores were more significant in the areas of rigor and independence. In the participants, the application field scores were generally low. The RIGHT evaluation results showed that the quality of five guides/recommendations should be improved. The six items with poor report quality were background, evidence, recommendations, review and quality assurance, funding and conflict of interest statement and management, and other aspects. Conclusion: The quality of the included gastric cancer screening guidelines/recommendations is generally low, and the standardization should be strengthened.

[Study on the health literacy and related factors of the cancer prevention consciousness among urban residents in China from 2015 to 2017].

Objective: To understand the health literacy and relevant factors of cancer prevention consciousness in Chinese urban residents from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The self-designed questionnaire was used to collect the information of demographic characteristics and cancer prevention consciousness focusing on nine common risk factors, including smoking, alcohol, fiber food, food in hot temperature or pickled food, chewing betel nut, helicobacter pylori, moldy food, hepatitis B infection, estrogen, and exercise. The logistic regression model was adopted to identify the influencing factors. Results: The overall health literacy of the cancer prevention consciousness was 77.4% (24 980 participants), with 77.4% (12 018 participants), 79.9% (6 406 participants), 77.2% (1 766 participants) and 74.5% (4 709 participants) in each group (P<0.001). The correct response rates for nine risk factors ranged from 55.2% to 93.0%. The multivariate logistic regression analysis showed that compared with community residents, people with primary school level education or below, and the number of people living together in the family <3, the cancer risk assessment/screening intervention population, cancer patients, those with junior high school level educationor above and the number of people living in the family ≥3 had better health literacy of the cancer prevention consciousness (all P values <0.05). Compared with females, 39 years old and below, government-affiliated institutions or civil servants, from the eastern region, males, older than 40 years, company or enterprise employees, and from the middle or western region had worse health literacy of the cancer prevention consciousness (all P values <0.05). Conclusion: The health literacy of the cancer prevention consciousness in Chinese urban residents should be improved. The cancer screening intervention, gender, age, education, occupation, the number of people co-living in the family, and residential region were associated with the health literacy of the cancer prevention consciousness.

[Analysis on the consciousness of the cancer early detection and its influencing factors among urban residents in China from 2015 to 2017].

Objective: To understand the consciousness of the cancer early detection among urban residents and identify the influencing factors from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. Self-designed questionnaires were used to collect population, socioeconomic indicators, self-cancer risk assessment, regular participation in physical examination and other information. The multivariate logistic regression model was used to identify the factors of people who had not regularly participated in the regular physical examination in the past five years. Results: The self-assessment results of 32 357 residents showed that there were 27.54% (8 882) of total study population with self-reported cancer risk, 45.48% (14 671) without cancer risk and 26.98% (8 704) with unclear judgement on their own cancer risk. Among population with cancer risk, 79.84% (7 091) considered physical examination accounted. In the past five years, there were 21 105 (65.43%) residents participated in regular physical examination and 11 148 (34.56%) participated in non-scheduled one, respectively. The multivariate logistic regression analysis showed that compared with unmarried and western region residents, divorced, middle and eastern region residents had a stronger consciousness to participate in the regular physical examination (P<0.05). Compare with residents with annual household income less than 20 000 CNY in 2014, cancer risk assessment/screening intervention population, and self-assessment with cancer risk, residents with annual household income between 20 000 CNY and 59 000 CNY in 2014, occupational population, community residents, cancer patients, self-reported cancer-free risk, and self-assessment with unclear judgement of cancer risk were less likely to participate in the regular physical examination (all P values <0.05). Conclusion: From 2015 to 2017, the Chinese urban residents had a acceptable consciousness of the cancer early detection. The marital status, annual household income, population group and self-assessment of cancer risk were related to the consciousness of the cancer early detection of people who had not participated in the regular physical examination in the past five years.