Objective:To understand spatial aggregation of lung cancer mortality and its changing trends over the past fifty years in different counties and districts of Shandong Province from 1970 to 2021.Methods:The mortality data of lung cancer were obtained from the death registration system of Shandong province and three retrospective surveys of death cause. The mortality rate and age-standardized mortality rate were used to describe the changing trend of lung cancer in different years, and the contribution value of population factors and non-population factors in lung cancer mortality change was calculated by the mortality differential decomposition method. GeoDa 1.20 and ArcGIS 10.8 software were used for spatial autocorrelation analysis and visualization map display.Results:The crude mortality rate of lung cancer in Shandong Province showed a significant upward trend from 1970 to 2021, rising from 7.22 per 100 000 in 1970-1974 to 62.73 per 100 000 in 2020-2021, with an increase of 7.69 times. Meanwhile, the standardized mortality rate of lung cancer exhibited a trend of increasing first and then decreasing. The differential analysis of lung cancer mortality in different years revealed that changes in crude mortality rates were the result of the combined effects of demographic and non-demographic factors. The proportion of population factors (aging population) leading to an increase in lung cancer mortality rate rose from 2.12% in 1990-1992 to 40.20% in 2020-2021. From a spatial distribution perspective, there were significant regional differences in lung cancer mortality rates among counties (cities, districts) in Shandong Province across different eras. Compared to the period of 1970-1974, the lung cancer mortality rates in all counties and districts in 2020-2021 showed a considerable increase, and there were noticeable changes in the areas of high-high and low-low clustering of lung cancer mortality rates across different eras.Conclusion:There have been significant temporal and spatial changes in the mortality rate of lung cancer in Shandong Province from 1970 to 2021. The crude mortality rate has shown an upward trend, while the standardized mortality rate increases first and then decreases. The concentration of lung cancer mortality rates in counties and districts has also undergone significant changes.

Objective:To describe the distribution characteristics and trends of mortality and spatial aggregation of esophageal cancer in Shandong Province from 1970 to 2021.Methods:The mortality data of esophageal cancer were obtained from the death registration system of Shandong Province and three national all-cause mortality retrospective surveys. The crude mortality rate (CMR) and age-standardized mortality rate (ASMR, the Segi′s world standard population) were used to describe the mortality of esophageal cancer. Mortality differential decomposition was applied to quantify the contributions of demographic and non-demographic factors. The death levels of esophageal cancer in different counties (cities and districts) in Shandong Province from 1970 to 1974 and 2020 to 2021 were visualized by the ArcGIS 10.8 software, and global and local autocorrelation analyses were conducted by using the GeoDa 1.12 software.Results:The CMR of esophageal cancer in Shandong Province increased first and then decreased from 1970 to 2021. The CMR of esophageal cancer decreased from 17.59/100 000 in the period of 1970—1974 to 14.32/100 000 in the period of 2020—2021. The ASMR of esophageal cancer decreased from 20.04/100 000 in the period of 1970—1974 to 6.53/100 000 in the period of 2020—2021. Compared with the period of 1970—1974, both demographic and non-demographic factors contributed to the increase in esophageal cancer mortality rate from 1990 to 1992. However, demographic factors continued to contribute to the increase in esophageal cancer mortality rate from 2004 to 2005, 2011 to 2013, and 2020 to 2021, while non-demographic factors contributed to the continuous decrease in esophageal cancer mortality rate. The global autocorrelation analysis results showed that the Moran′s I index of ASMR of esophageal cancer in each county (city, district) of Shandong Province from 1970 to 1974 and from 2020 to 2021 were 0.67 and 0.57, respectively. Local autocorrelation analysis showed that there were 19 and 13 areas of high-high clustering of esophageal cancer in the periods of 1970—1974 and 2020—2021, respectively, with 12 overlapping counties (cities, districts). Conclusion:From 1970 to 2021, the CMR of esophageal cancer increases first and then decreases, while the ASMR of esophageal cancer gradually decreases in Shandong Province. The distribution of esophageal cancer mortality has significant spatial aggregation and changes over time.

SPF chickens were immunized with HN-mRNA vaccine by intramuscular injection.He-magglutination inhibition(HI)test,lymphocyte proliferation test,RT-qPCR and pathological sec-tions were used to evaluate the humoral and cellular immunity and protection against challenge in-duced by the candidate HN-mRNA vaccine.The results showed that 2.5,5.0,and 7.5 μg HN-mR-NA induced HI antibody antibodies in a dose-dependent manner.Among them,the Hi antibody in-duced by 7.5 μg HN-mRNA was slightly higher than that of the weak toxic vaccine(La Sota strain).In addition,in response to the stimulation of inactivated NDV virus,the proliferation and activation of lymphocytes in 2.5,5.0 and 7.5 μg HN-mRNA immunization groups and commercial vaccine group were observed.To further evaluate the antiviral protection provided by HN mRNA immunization,the 105 ELD50 NDV strong strain NA-1 was used to attack the 7.5 μg HN-mRNA immunised group and the commercial weakened vaccine(La Sota strain)and PBS groups using na-sal and ocular drops.The results showed that the survival rate of 7.5 μg HN-mRNA immunization group and commercial vaccine group was 100％,and these vaccines could protect tissues and or-gans from the damage caused by virus infection.At the same time,7.5 μg HN-mRNA and commer-cial vaccine could shorten the time of virus shedding in vitro and the viral load in vivo.This study provides a foundational framework for the clinical application of NDV HN mRNA candidate vac-cines and offers insights for the development of novel mRNA vaccines for poultry.

Objective·To investigate the bidirectional causal relationships between celiac disease(CeD)and Hashimoto thyroiditis(HT)as well as Graves disease(GD),using a two-sample Mendelian randomization(MR)approach.Methods·Single nucleotide polymorphisms(SNPs)related to CeD,HT and GD were extracted from publicly available Genome-Wide Association Studies(GWAS)databases and used as instrumental variables.The inverse-variance weighted(IVW)method served as the primary analytical approach,supplemented by MR-Egger,weighted median(WME)and weighted mode(WMO)methods,to evaluate the causal associations between CeD and both HT and GD.Replication analyses using alternative GWAS datasets were conducted to validate the robustness of the results.Heterogeneity was assessed using Cochran's Q test,and pleiotropy was evaluated via MR-Egger intercept test.Leave-one-out analyses were performed to assess the impact of individual SNPs on the results.Results·The IVW analysis results indicated that genetically predicted CeD significantly increased the risk of HT[discovery group:OR=1.186(95%CI 1.114?1.262),P<0.001;replication group:OR=1.218(95%CI 1.090?1.361),P<0.001]and GD[discovery group:OR=1.214(95%CI 1.155?1.276),P<0.001;replication group:OR=1.273(95%CI 1.161?1.396),P<0.001].However,reverse MR analyses did not provide evidence for a causal relationship between HT and CeD,while genetically predicted GD significantly increased the risk of CeD[discovery group:OR=1.259(95%CI 1.006?1.576),P=0.044;replication group:OR=1.387(95%CI 1.233?1.560),P<0.001].Sensitivity analyses suggested that the results were not influenced by horizontal pleiotropy.Conclusion·CeD may be causally associated with a higher risk of HT and GD,while GD may increase the risk of developing CeD.HT does not appear to have an impact on CeD.

Objective To explore factors affecting blood pressure control in chronic disease patients in China's na-tional basic public health service chronic disease patient management program and to find their relationships with Bayesian network(BN)model,in order to provide a scientific basis for comprehensive hypertension management.Methods 5 577 Hypertensive patients were selected from eight provinces(including autonomous regions)covering eastern,central and western parts of China during a survey from 2021 to 2022.Researchers collected individual and community-management data to screen influencing factors by Logistic regression,and to describe factor dependencies and to identify key determinants of blood pressure control with BN in.blood pressure control.Results Logistic regression revealed that urban/rural status,education,alcohol use,exercise,overweight/obesity and com-munity-doctor advice on salt reduction,smoking cessation were significantly associated with blood pressure control(P＜0.05).The BN model identified 22 directed edges showing that urban residence and good hypertension knowl-edge were more correlated with better control,while community-doctor management and services directly affected patient lifestyle habits but not blood pressure control.Conclusions Research should focus more on urban-rural dis-parities and hypertension education.Additionally,improving patient habits and community-doctor services is essen-tial for better blood pressure control.

Objective:To understand spatial aggregation of lung cancer mortality and its changing trends over the past fifty years in different counties and districts of Shandong Province from 1970 to 2021.Methods:The mortality data of lung cancer were obtained from the death registration system of Shandong province and three retrospective surveys of death cause. The mortality rate and age-standardized mortality rate were used to describe the changing trend of lung cancer in different years, and the contribution value of population factors and non-population factors in lung cancer mortality change was calculated by the mortality differential decomposition method. GeoDa 1.20 and ArcGIS 10.8 software were used for spatial autocorrelation analysis and visualization map display.Results:The crude mortality rate of lung cancer in Shandong Province showed a significant upward trend from 1970 to 2021, rising from 7.22 per 100 000 in 1970-1974 to 62.73 per 100 000 in 2020-2021, with an increase of 7.69 times. Meanwhile, the standardized mortality rate of lung cancer exhibited a trend of increasing first and then decreasing. The differential analysis of lung cancer mortality in different years revealed that changes in crude mortality rates were the result of the combined effects of demographic and non-demographic factors. The proportion of population factors (aging population) leading to an increase in lung cancer mortality rate rose from 2.12% in 1990-1992 to 40.20% in 2020-2021. From a spatial distribution perspective, there were significant regional differences in lung cancer mortality rates among counties (cities, districts) in Shandong Province across different eras. Compared to the period of 1970-1974, the lung cancer mortality rates in all counties and districts in 2020-2021 showed a considerable increase, and there were noticeable changes in the areas of high-high and low-low clustering of lung cancer mortality rates across different eras.Conclusion:There have been significant temporal and spatial changes in the mortality rate of lung cancer in Shandong Province from 1970 to 2021. The crude mortality rate has shown an upward trend, while the standardized mortality rate increases first and then decreases. The concentration of lung cancer mortality rates in counties and districts has also undergone significant changes.

Objective:To describe the distribution characteristics and trends of mortality and spatial aggregation of esophageal cancer in Shandong Province from 1970 to 2021.Methods:The mortality data of esophageal cancer were obtained from the death registration system of Shandong Province and three national all-cause mortality retrospective surveys. The crude mortality rate (CMR) and age-standardized mortality rate (ASMR, the Segi′s world standard population) were used to describe the mortality of esophageal cancer. Mortality differential decomposition was applied to quantify the contributions of demographic and non-demographic factors. The death levels of esophageal cancer in different counties (cities and districts) in Shandong Province from 1970 to 1974 and 2020 to 2021 were visualized by the ArcGIS 10.8 software, and global and local autocorrelation analyses were conducted by using the GeoDa 1.12 software.Results:The CMR of esophageal cancer in Shandong Province increased first and then decreased from 1970 to 2021. The CMR of esophageal cancer decreased from 17.59/100 000 in the period of 1970—1974 to 14.32/100 000 in the period of 2020—2021. The ASMR of esophageal cancer decreased from 20.04/100 000 in the period of 1970—1974 to 6.53/100 000 in the period of 2020—2021. Compared with the period of 1970—1974, both demographic and non-demographic factors contributed to the increase in esophageal cancer mortality rate from 1990 to 1992. However, demographic factors continued to contribute to the increase in esophageal cancer mortality rate from 2004 to 2005, 2011 to 2013, and 2020 to 2021, while non-demographic factors contributed to the continuous decrease in esophageal cancer mortality rate. The global autocorrelation analysis results showed that the Moran′s I index of ASMR of esophageal cancer in each county (city, district) of Shandong Province from 1970 to 1974 and from 2020 to 2021 were 0.67 and 0.57, respectively. Local autocorrelation analysis showed that there were 19 and 13 areas of high-high clustering of esophageal cancer in the periods of 1970—1974 and 2020—2021, respectively, with 12 overlapping counties (cities, districts). Conclusion:From 1970 to 2021, the CMR of esophageal cancer increases first and then decreases, while the ASMR of esophageal cancer gradually decreases in Shandong Province. The distribution of esophageal cancer mortality has significant spatial aggregation and changes over time.

Purpose To explore the clinical and pathological features,differential diagnosis,treatment methods and prognosis of urachal adenocarcinoma.Methods Nineteen cases of urachal adenocarcinoma were collected and an-alyzed by combining clinical symptoms,auxiliary examinations,histology,immunohistochemical,and genetic testing and 11 cases of bladder adenocarcinomas.Results Among the 19 patients(15 males,4 females;age range:33-75 years,mean:55 years),tumors were located at the dome or anterior wall of the bladder.Histological subtypes includ-ed mucinous adenocarcinoma(6 cases),adenocarcinoma not otherwise specified(4 cases),enteric-type adenocarci-noma(6 cases),adenocarcinoma with focal mucinous differentiation(1 case),adenocarcinoma with signet-ring cell carcinoma(1 case),and metastatic urachal adenocarcinoma(1 case).Immunophenotypic analysis revealed membra-nous positivity for β-catenin,diffuse positivity for CK34βE 12,MUC-2,and CK20,focal CK7 positivity in some cases,and rare GATA-3 positivity.Mutations in p53 were observed,while KRAS,NRAS,BRAF,and PIK3CA mutations were absent.In colorectal adenocarcinomas,CK34βE12 positivity was 40％,nuclear β-catenin positivity was 48％,and MUC-2 expression was approximately 50％.In bladder adenocarcinomas,GATA-3 and MUC-2 positivity rates were 45％and 63.6％,respectively.Conclusion Distinguishing urachal adenocarcinoma from colorectal and primary bladder adenocarcinomas remains challenging.Urachal adenocarcinoma should be suspected in patients with anterior bladder wall or dome lesions,gross hematuria,or mucinuria.No definitive diagnostic markers currently exist for ura-chal adenocarcinoma.Immunophenotypic features such as membranous β-catenin,MUC-2,and CK7 positivity may fa-vor urachal adenocarcinoma over colorectal adenocarcinoma.Additional markers(e.g.,GATA-3,CK20,CK34βE12)aid in differential diagnosis,though individual markers lack specificity.Comprehensive evaluation integrating clinical presentation,imaging,and clinicopathological features is essential for accurate diagnosis.

Respiratory syncytial virus (RSV) is one of the most important pathogens causing respiratory infections in children, and a major cause of hospitalization and death.However, current therapeutic measures are based on supportive care and there is a lack of specific antiviral drugs, so prevention of RSV infection is extremely important.Active and passive immunization is the main way to prevent infection, but monoclonal antibodies are not widely applied in clinical practice because they are high-priced and some of them need multiple doses.Therefore, it is important to develop a usable RSV vaccine.Progress of vaccine research was slow previously due to the vaccine-enhanced disease caused by Formalin-inactivated vaccines and the difficult pre-preparation and poor stability of attenuated vaccines.With the gradual clarification of the structural characteristics of RSV fusion proteins, the maturation of biotechnology, and the emergence of component vaccines recently, vaccine research and development has made great progress, and the maternal vaccine Abrysvo has now been approved for the prevention of RSV infections in infants and young children.This review provides an overview of the biological structure of RSV and the current status of research on pediatric RSV vaccine.

Objective:We aimed to analyze the spatio-temporal trend of breast cancer incidence and mortality in Shandong Province from 2012 to 2023 and predict the development trend from 2024 to 2030.Methods:Data on the incidence and mortality of breast cancer in Shandong Province from 2012 to 2023 were obtained from the Shandong Cancer Registry. The incidence, age-specific incidence, mortality, and age-specific mortality in different years, as well as in urban and rural areas, were calculated, and the rates were standardized based on the age composition of the Chinese standard population in 2000. The average annual percent change (AAPC) rate was calculated using Joinpoint 4.8.0.1 software. The global and local spatial autocorrelation analysis were performed using GeoDa 1.12 software. The Bayesian age-period-cohort model was used to predict the trend of breast cancer incidence and mortality from 2024 to 2030.Results:From 2012 to 2023, the breast cancer age-standardized incidence rate (ASIR) showed an increasing trend. The ASIR increased from 30.48/100 000 in 2012 to 39.94/100 000 in 2023 (AAPC=2.59%, P<0.001). The ASIR of urban and rural females also showed an upward trend. Additionally, the ASIR in rural areas (AAPC=3.33%, P<0.001) increased more than that in urban areas (AAPC=1.83%, P=0.002). The incidence peak of breast cancer mainly concentrated in population aged 45-64 years, and with the increase of years, the incidence peak gradually moved forward. The age-standardized mortality rate (ASMR) showed a downward trend. The ASMR decreased from 6.89/100 000 in 2012 to 4.93/100 000 in 2023 (AAPC=-3.12%, P<0.001). The ASMR of urban and rural females also showed a downward trend (urban: AAPC=-3.56%, P=0.007; rural: AAPC=-2.72%, P<0.001). The spatial analysis showed that from 2015 to 2023, the clustering areas of breast cancer incidence and mortality in Shandong had changed significantly. In 2015, the "High-high clusters" of ASIR mainly included Wendeng District in Weihai City, Dongying District, Kenli District, Lijin County, Guangrao County in Dongying City, Tianqiao District, Shizhong District in Jinan City; In 2023, the "High-high clusters" mainly included Jiaxiang County, Liangshan County, Jinxiang County, Wenshang County, Rencheng District in Jining City, Hedong District in Linyi City, Guangrao County in Dongying City. In 2015, the "High-high clusters" of ASMR only included Wenshang County in Jining City. In 2023, the "High-high clusters" mainly included Laizhou County in Yantai City, Junan County and Yishui County in Linyi City, Gaotang County in Liaocheng City, Dongping County and Ningyang County in Taian City. The Bayesian age-period-cohort model predicted that the ASIR trend of breast cancer in Shandong tended to be smooth (AAPC=0.33%, P=0.001). However, the ASMR remained decreasing (AAPC=-4.68%, P<0.001). Conclusions:The breast cancer incidence in Shandong showed an increasing trend, and it is expected to be smooth by 2030. However, the mortality showed a continuous downward trend. The incidence peak was mainly in the population aged 45-64 years, with obvious regional differences. Targeted prevention and control measures should be taken for high-risk groups and areas in Shandong Province.