Prostaglandin E2(PGE2)regulates a variety of cells in tumor microenvironment(TME)and plays an important role in tumor growth,metastasis and immunity.PGE2 activates different downstream signaling pathways through its key receptor prostaglandin E receptor(EP4),regulating inflammation,immune cell function and angiogenesis to promote or inhibit tumor development.EP4 shows potential application values in adjuvant chemotherapy and immunotherapy as an emerging anti-tumor target.However,future studies on the roles of EP4 in tumor microenvironment,develo-pment of safer and more effective EP4 drugs,and its application in personalized immunotherapy are needed.

[Purpose]To analyze cancer incidence and mortality in Anhui cancer registration areas in 2019 and the trends from 2015 to 2019.[Methods]Data from 42 cancer registration areas in Anhui Province in 2019 meeting quality control requirements were collected.The incidence,mor-tality,age-standardized rates by Chinese standard population and world standard population,age-specific rate,accumulation rate(0～74 years old)and the top 10 cancers of high incidence and mortality were calculated by urban and rural areas,sexes and age groups.The standard population of China in 2000 was used for age-standardized incidence or mortality rate(ASIRC or ASMRC),and the Segi world standard population was used for age-standardized incidence or mortality rate(ASIRW or ASMRW),respectively.Joinpoint was used to analyze the incidence and mortality trends from 2015 to 2019,and the annual percentage change(APC)was estimated.[Results]In 2019,the reported incidence rate(crude rate)in Anhui cancer registration areas was 282.87/105(313.24/105 for male,251.19/105 for female),ASIRC and ASIRW were 183.85/105 and 178.94/105,respectively,with the cumulative incidence rate of 20.35％.There was no significant change in the incidence of malignant tumors from 2015 to 2019(APC=-1.00％,P＞0.05).The reported mortality rate(crude rate)was 167.20/105(214.67/105 for male,117.67/105 for female),ASMRC and ASMRW were 98.41/105 and 97.15/105,and the cumulative mortality rate was 10.68％.There was no significant change in the mortality rate of malignant tumors from 2015 to 2019(APC=-3.44％,P＞0.05).The incidence and mortality rate of lung cancer ranked the first in urban and rural popu-lations of all genders.The incidence rate of female breast cancer ranked the third and the mortali-ty rate ranked the sixth of all malignancies.The incidence and mortality of malignant tumors in men were higher than those in women,and higher in rural areas than those in urban areas,and the main cancer types of rural and urban areas tended to be the same.[Conclusion]From 2015 to 2019,there was no significant change in the incidence and mortality of malignant tumors in the cancer registration areas of Anhui Province,but it is still necessary to prevent and treat lung can-cer and female breast cancer.

[Purpose]To analyze the trends of cervical cancer incidence in Qidong City of Jiangsu Province from 1977 to 2021.[Methods]Based on the cervical cancer registration database in Qi-dong City from 1977 to 2021,the crude incidence rate,the age-standardized rate by the standard Chinese standard population and the world standard population(ASRC and ASRW),the truncated rate of 35～64 years old,the cumulative rate of 0～74 years old,and the cumulative risk were cal-culated;the incidence rates of birth cohorts were analyzed.Joinpoint regression analysis was per-formed with Joinpoint 4.9.0.0 software to calculate the annual percentage change(APC)and the average annual percentage change(AAPC)of cervical cancer incidence.[Results]A total of 2 253 new cases of cervical cancer registered in Qidong City from 1977 to 2021,accounting for 1.62％of the total case numbers of cancer in the whole population,and for 4.03％of the total number of cancers in women.The crude incidence rate was 8.75/105,the ASRC was 4.54/105,the ASRW was 6.01/105,the truncated rate(35～64 years old)was 15.09/105,the cumulative rate(0～74 years old)was 0.63％,and the cumulative risk was 0.63％.The incidence of cervical cancer increased with age from 1977 to 2021.The average incident age was 55.36 years old,with the lowest age of 47.51 years old in 2010.Secular trend analysis showed that the AAPC of the crude incidence of cervical cancer was 6.010％(95％CI:4.951％～7.081％)(P＜0.001),among which the trend decreased from 1977 to 1999,with an APC of-2.507％;and then the trend increased from 1999 to 2017,with an APC of 14.436％(P＜0.001).The rising and falling trend curves of the AS-RC and ASRW were similar to that of the crude incidence.The age group and time period analysis showed that the peak incidence was in the older age groups before 2006,while the peak inci-dence appeared in the age groups of 45～54 years old from 2007 to 2021.The AAPCs in age groups of 25～64 years old demonstrated upward trends(all P＜0.05).The birth cohort analysis showed that the cervical cancer incidence in the 1937-1941 birth cohort was the lowest,and the birth cohort-specific rates in all age groups showed"V-shape"trends.[Conclusion]Long-term monitoring of cervical cancer incidence in Qidong has shown a trend of initially slow decline fol-lowed by a rapid increase,with the peak incident shifting towards younger ages.The rising trends of cervical cancer incidence in last two decades may be associated with the increased HPV infection,suggesting that measures to reduce HPV infection and enhance vaccination should be strengthened.

In order to achieve the quality homogenization of medical services among regions,Chi-na actively explores and promotes the construction of regional national medical centers.This paper illustrates the substantive cooperation during the integration period of the establishment of the re-gional center between output hospital(Sun Yat-Sen University Cancer Center)and the input hospi-tal(Gansu Cancer Hospital).During the integration period a collaborative management model with vertical and horizontal linkages was formed,and the cross-regional long-distance cooperation bar-riers were effectively overcome.Based on the patients-oriented medical service,the two hospitals have achieved remarkable results in the construction and development of clinical service,teach-ing,research and management of Gansu Hospital,which would provide a practical reference for the construction and management of regional national medical center.

In recent years,viral vector-mediated chimeric antigen receptor(CAR)cell therapy has emerged as a prominent topic in the field of cancer treatment and has demonstrated significant clinical efficacy in patients with hematological malignancies.However,the permanent expression of CAR induced by this therapy may give rise to severe adverse reactions.In contrast,messenger RNA(mRNA)chimeric antigen receptor therapy is anticipated to become a new generation of safer and more effective treatments due to its lack of insertional mutagenesis and minimal risk of off-tar-get toxicity.This therapeutic approach involves transfecting effector immune cells with CAR-en-coding mRNA to elicit an immune response within the body.It has been employed for treating B-cell malignancies,lymphoma,acute myelogenous leukemia(AML),and other cancers.The continuous optimization of mRNA purification,modification,and transfection technology enhances CAR ex-pression durability,while increasing killing efficiency and expanding the range of action.This pa-per reviews the research advances on CAR-encoding mRNA delivery,its application and advan-tages in cancer therapies.

[Purpose]To analyze the trends of incidence and age at onset of leukemia in Jiangsu cancer registration areas from 2009 to 2019.[Methods]The continuous monitoring data of leukemia from 2009 to 2019 were collected from 16 cancer registries in Jiangsu Province.All datasets were checked and evaluated based on data quality control criteria and were included in the analysis.Crude incidence rate(CIR),age-standardized incidence rate by Chinese standard population(ASIRC),the average annual percentage change(AAPC),the standardized average age at onset,the changes in the age structure of incidence and the changes in the birth cohort by year were calculated.[Results]The incidence rate of leukemia significantly increased from 5.22/105 in 2009 to 7.88/105 in 2019,with a significant upward trend(for CIR,AAPC=4.95％,95％CI:3.82％～6.09％;for ASIRC,AAPC=2.97％,95％CI:1.52％～4.43％).The incidence rates were in-creased in all age groups and increased with the birth cohort by years.There was a tendency of backward shift for the age composition of the population,with the increasing of composition for those over 60 years old.The mean age at onset increased from 48.62 years old in 2009 to 57.96 years old in 2019,with a backward shift in the mean age(β=0.773,P＜0.001),and the mean age at onset increased with the year only in rural areas after standardization(β=0.428,P=0.017).[Conclusion]Leukemia incidence rate in Jiangsu Province increased from 2009 to 2019,and the age at onset has shifted backwards.It's important to strengthen the early prevention and control of leukemia.

[Purpose]To analyze the cost-effectiveness and cost-utility conducted on the lung can-cer screening project in urban areas of Anhui Province,and to provide suggestions for the formu-lation of lung cancer screening policies in Anhui Province.[Methods]A Markov decision model for low-dose computed tomography(LDCT)lung cancer screening intervention was established based on on-site survey data and literature data.The development of the population under different interventions was simulated,using saved life years(LYS)and quality-adjusted life years(QALY)as effectiveness indicators,to conduct cost-effectiveness and cost-utility analyses of different screening strategies.Cost data were discounted at a 3％discount rate.[Results]The screening schemes of once a year,once every two years,once every three years,and once every five years all meet the cost-effectiveness principle for saving one LYS or QALY.Among them,the best screening strategy in terms of cost-effectiveness and cost-utility was the LDCT lung cancer screening strategy once every two years,with costs of 72 441.54 CNY and 71 050.24 CNY,respectively.[Conclusion]The LDCT lung cancer screening program demonstrates good cost-effectiveness,with strategies of dif-ferent screening frequencies being viable options.The optimal screening strategy is screening once every two years.

[Purpose]To analyze the incidence,mortality and disease burden of malignant tumors in the cancer registration areas of Hebei Province in 2020.[Methods]The incidence and mortality data of cancer in 2020 were collected from the cancer registries of Hebei Province,and the quality of data was evaluated.The crude incidence(mortality)rate,age-specific incidence(mortality)rates and age-standardized incidence(mortality)rates by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW)were calculated and analyzed.The disability-ad-justed life years(DALY)were calculated and analyzed according to the Excel disease burden cal-culation template recommended by the World Health Organization(WHO).[Results]In 2020,the crude incidence rate,ASIRC,ASIRW of malignant tumors in the cancer registration areas of Hebei Province were 229.36/105,147.06/105 and 143.74/105,respectively.The incidence rate in men was higher than that in women.The incidence rates in urban and rural areas were 230.26/105 and 228.84/105,and the age-standardized incidence rates reached a peak in the age group of 80～84 years old.The crude mortality rate,ASMRC,ASMRW were 146.38/105,85.33/105 and 84.79/105,respectively.The mortality rate in men was higher than that in women.The age-standardized mor-tality rate rose with age,reaching a peak in the age group of 85+years old,and the crude mortality rates in urban and rural areas were 143.82/105 and 147.84/105,respectively.The DALY of ma-lignant tumors in the cancer registration areas of Hebei Province were 345 030 person-years,reaching a maximum in the age group of 45～59 years old,with a DALY rate of 15.00/103,and the highest in the age group of 70～79 years old.Lung cancer had the heaviest disease burden,with DALY of 83 684 person-years,accounting for 24.25％of all malignant tumors,followed by stomach,liver,female breast,and colorectal cancers.The DALY in urban and rural areas were 122 062 and 222 993 person-years,respectively,and the trends in DALY rates were basically stable.[Conclusion]The disease burden of malignant tumors in Hebei Province is relatively heavy,cancer prevention and control should be further strengthened and focused on urban men and the elderly to reduce disease burden of malignant tumors in the future.

[Purpose]To analyze the lifetime risk of developing and dying from lung cancer at global and regional levels.[Methods]Data of lung cancer incidence and mortality were obtained from GLOBOCAN 2022 and the population and all-cause mortality data were obtained from the United Nations.The lifetime risk of developing and dying from lung cancer globally and across different regions was estimated by multiple primary adjustment method.[Results]The global lifetime risk of developing lung cancer was 3.59％[95％confidence interval(CI):3.58％～3.59％],ranking third among all cancer types.There were significant gender and regional differences in lifetime risk values.The risk for male was 4.43％(95％CI:4.42％～4.44％),which was higher than that for female(2.71％,95％CI:2.70％～2.72％),with a male-to-female ratio of 1.63.Among regions with varying human development index(HDI)levels,the risk increased with HDI levels,in very high HDI re-gions risk was 5.36％(95％CI:5.34％～5.37％),while in low HDI regions the risk was 0.34％(95％CI:0.33％～0.34％).Among the 20 global regions,East Asia had the highest lifetime risk of 7.53％(95％CI:7.52％～7.55％),while West Africa had the lowest risk of 0.16％(95％CI:0.16％～0.17％).The global lifetime risk of dying from lung cancer was 2.78％(95％CI:2.78％～2.78％),ranking the first among all cancer types.There were significant sex and regional differ-ences in lifetime death risk values.The risk for male was 3.64％(95％CI:3.63％～3.64％),which was higher than that for female(1.89％,95％CI:1.89％～1.90％),with a male-to-female ratio of 1.93.Among regions with varying HDI levels,the risk increased with HDI levels,in very high HDI re-gions the risk was 3.98％(95％CI:3.97％～3.99％),while in low HDI regions the risk was 0.31％(95％CI:0.31％～0.31％).Among the 20 global regions,the Federated States of Micronesia/Poly-nesia had the highest death risk of 5.80％(95％CI:4.98％～6.62％),while West Africa had the lowest risk of 0.15％(95％CI:0.15％～0.16％).The lifetime risk of developing and dying from lung cancer in China was 7.54％(95％CI:7.52％～7.56％)and 5.88％(95％CI:5.87％～5.90％),respec-tively,both ranking the first among all cancer types.[Conclusion]The lifetime risk of developing and dying from lung cancer remains high globally and across different regions,with a particularly heavy burden in high-HDI areas.In China,both the lifetime risk of developing and dying from lung cancer are higher than the global average.This highlights the need for continued enhance-ment of comprehensive prevention and control measures,including addressing lung cancer-related risk factors,as well as improving screening,early diagnosis,and treatment efforts to reduce the lung cancer burden.

[Purpose]To investigate the acceptance and willingness-to-pay(WTP)of combined can-cer screening among rural residents in Shandong Province,and to analyze its influencing factors.[Methods]A face-to-face questionnaire survey was conducted among rural residents aged 40～70 in villages setected by cluster sampling from three counties(county level city or district)in Shan-dong Province.The questionnaire was developed using the method of double-bound dichotomous choice combined with open-ended questions in contingent valuation.The factors influencing inten-sity of WTP was analyzed with using single-factor and ordinary least squares regression models.[Results]A total of 962 subjects were surveyed.89.19％of the respondents were willing to accept cancer combined screening,and 62.00％were willing to pay part of the costs.The average of WTP was 963.67 CNY,which accounted for 32.12％of the total cost.The proportion of respon-dents who were willing to pay between 0～1 500 CNY was the highest(76.49％).In the multivariate analysis,age,sex and income had significant effects on the maximum payment of multi-cancer screening.[Conclusion]The acceptance of multi-cancer screening among rural residents in the study sites is high,but the willingness-to-pay is limited.The out-of-pocket payment for multi-can-cer screening should be controlled,and a co-payment mechanism among government,enterprises,social organizations and individuals should be explored.