OBJECTIVES: In recent years, the role of remnant cholesterol (RC) in the development and progression of cardiovascular diseases has gained increasing attention. However, evidence on the association between RC and subclinical atherosclerosis is limited. This study aims to examine the relationship between RC and atherosclerotic plaques in single and multiple vascular territories. METHODS: This retrospective cross-sectional study used baseline data from participants enrolled between October 2022 and May 2024 in the National Key Research Program "Study on the Prevention and Control System of Risk Factors for Panvascular Diseases". Color Doppler ultrasonography was performed to detect plaques in 4 vascular territories: Bilateral carotid arteries, bilateral subclavian arteries, abdominal aorta, and iliac-femoral arteries. RC was calculated as total cholesterol minus the sum of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Participants were categorized into quartiles (Q1-Q4) according to RC levels. The proportions of participants with ≥2 plaques in a single vascular territory and with plaques in ≥2 vascular territories were compared across RC quartiles. Multivariate ordinal Logistic regression was used to assess the association between RC and the number of plaques in a single vascular territory, as well as the risk of multiple vascular territory involvement. Additionally, the effects of LDL-C/RC concordance on plaque distribution were analyzed. RESULTS: A total of 3 539 participants were included, of whom 2 169 (61.29%) were male, with a age of (51.94±9.22) years. From Q1 to Q4, the proportion of participants with ≥2 plaques in a single vascular territory (bilateral carotid, subclavian, abdominal aorta, and iliac-femoral arteries), as well as those with plaques in ≥2 vascular territories, increased progressively. Compared with Q1, both Q3 and Q4 were significantly associated with higher plaque numbers in a single vascular territory (both P<0.05). When treated as a continuous variable, higher RC levels were associated with an increased risk of greater plaque numbers within a single vascular territory (all P<0.05). RC levels were also significantly associated with multiple vascular territory involvement: Compared with Q1, Q4 had a 1.015-fold higher risk [odds ratio (OR)=2.015, 95% confidence interval (CI) 1.669 to 2.433], and each 1 mmol/L increase in RC corresponded to a 0.160-fold increased risk (OR=1.160, 95% CI 1.073 to 1.271). In LDL-C/RC coordination analysis, compared with the low LDL-C/low RC group, the low LDL-C/high RC group was significantly associated with multiple vascular territory involvement (OR=1.576, 95% CI 1.220 to 2.036). CONCLUSIONS Elevated RC levels are closely associated with atherosclerotic plaques in both single and multiple vascular territories, even among individuals with normal LDL-C, suggesting that RC should be considered in clinical risk assessment and management of atherosclerosis.
Humans ; Plaque, Atherosclerotic/diagnostic imaging* ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Retrospective Studies ; Cholesterol/blood* ; Cholesterol, LDL/blood* ; Aged ; Cholesterol, HDL/blood* ; Risk Factors ; Atherosclerosis ; Ultrasonography, Doppler, Color ; Femoral Artery/diagnostic imaging*

Background::Liver cancer remains the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide, causing a heavy burden globally. An updated assessment of the global epidemiology of the liver cancer burden that addresses geographical disparities is necessary to better understand and promote healthcare delivery.Methods::Data were extracted from the GLOBOCAN 2022 database, including the number, crude, and age-standardized rates of incidence and mortality at the global, country, continent, and human development index (HDI) regional levels. Age-standardized rates (incidence and mortality) per 100,000 person-years were adjusted based on the Segi-Doll World standard population. The mortality-to-incidence ratios (MIR) for each region and country were calculated. The HDI and gross national income (GNI) for 2022 were obtained, and a Pearson correlation analysis was conducted with the incidence, mortality, and MIR.Results::In 2022, approximately 866,136 new liver cancer cases and 758,725 related deaths were recorded worldwide, with a global MIR of 0.86. Males had a disproportionately higher burden than females across all levels, and the highest burden was observed in the elderly population. Geographically, the regions with the highest incidence rates included Micronesia, Eastern Asia, and Northern Africa, and the regions with the highest mortality rates included Northern Africa, Southeastern Asia, Eastern Asia, and Micronesia. Notably, Mongolia had a strikingly high burden compared to other countries. The highest MIR was observed in North America and the lowest in Africa. Negative associations of HDI and GNI with liver cancer mortality and MIR were identified, irrespective of sex.Conclusions::The current liver cancer burden underscores the presence of remarkable geographic heterogeneity, which is particularly evident across countries with varying HDI levels, highlighting the urgent need to prioritize health accessibility and availability to achieve health inequities.

CRISPR/Cas9 technology has driven the development of various fields in life science.With continuous deepening of its understanding,researchers have made multiple improvements and optimizations to adapt to various application scenarios.The optimization of CRISPR/Cas9 technology has also provided breakthroughs in the establishment of genetically modified mouse models.This article briefly reviews the development process of CRISPR/Cas9 technology and summarizes optimization strategies of CRISPR/Cas9,establishment of conditional knockout/knockin gene-modified mouse models,and delivery systems for CRISPR/Cas9 elements and HDR templates.

BACKGROUND AND AIM: Remnant cholesterol (remnant-C) mediates the progression of major adverse cardiovascular events. It is unclear whether remnant-C, and particularly cumulative exposure to remnant-C, is associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether remnant-C, not only baseline but cumulative exposure, can be used to independently evaluate the risk of NAFLD. METHODS: This study included 1 cohort totaling 21,958 subjects without NAFLD at baseline who underwent at least 2 repeated health checkups and 1 sub-cohort totaling 2,649 subjects restricted to those individuals with at least 4 examinations and no history of NAFLD until Exam 3. Cumulative remnant-C was calculated as a timeweighted model for each examination multiplied by the time between the 2 examinations divided the whole duration. Cox regression models were performed to estimate the association between baseline and cumulative exposure to remnant-C and incident NAFLD. RESULTS: After multivariable adjustment, compared with the quintile 1 of baseline remnant-C, individuals with higher quintiles demonstrated significantly higher risks for NAFLD (hazard ratio [HR] 1.48, 95%CI 1.31-1.67 for quintile 2; HR 2.07, 95%CI 1.85-2.33 for quintile 3; HR 2.55, 95%CI 2.27-2.88 for quintile 4). Similarly, high cumulative remnant-C quintiles were significantly associated with higher risks for NAFLD (HR 3.43, 95%CI 1.95-6.05 for quintile 2; HR 4.25, 95%CI 2.44-7.40 for quintile 3; HR 6.29, 95%CI 3.59-10.99 for quintile 4), compared with the quintile 1. CONCLUSION Elevated levels of baseline and cumulative remnant-C were independently associated with incident NAFLD. Monitoring immediate levels and longitudinal trends of remnant-C may need to be emphasized in adults as part of NAFLD prevention strategy.
Adult ; Humans ; Cohort Studies ; Non-alcoholic Fatty Liver Disease/etiology* ; Cholesterol ; Proportional Hazards Models ; Risk Factors

Objective To overcome the limitations of existing human respiratory syncytial virus(hRSV)animal models,such as semi-permissiveness and short duration of infection,this study established an IL2rg gene knockout(IL2rg-/-)rat model using TALEN gene editing technology.Methods The animal model was infected with hRSV intranasally.Clinical characteristics,body weight,and temperature changes were observed over the infection period(0～35 days).The total viral loads in respiratory organs,such as the nasal tissue,trachea,and lungs,were measured at various time points(4,11,20,and 35 days post-infection).Pathological analysis was conducted on target organs at the endpoint of observation(35 days post-infection).Changes in peripheral blood T,B,NK,and NKT cells and various cytokines were assessed at various time points(4,20,and 35 days post-infection).Results(1)IL2rg/-knockout rats sustained high viral loads in the nasal cavity upon intranasal inoculation with hRSV.The average peak titer rapidly reached 1 × 1010 copies/g in nasal tissue and 1 × 107 copies/g up to 5 weeks post-infection.(2)However,no significant pathological changes were noted in nasal,tracheal,or lung tissues.(3)An increase was observed in the content of peripheral blood B cells in hRSV-infected IL2rg--rats.(4)IL-6 and MCP-1 were increased in the early stage of infection and then decreased at the end of the observation period.Conclusions This study established a new IL2rg-/-rat model using TALEN technology and found that this model effectively supported high-level replication and long-term infection of hRSV,providing a good basis for antiviral drug screening and in vivo efficacy evaluation of anti-hRSV antibodies.

BACKGROUND: Cancer patterns in China are becoming similar to those in the United States (US). Comparing the recent cancer profiles, trends, and determinants in China and the US can provide useful reference data. METHODS: This study used open-source data. We used GLOBOCAN 2022 cancer estimates and United Nations population estimates to calculate cancer cases and deaths in both countries during 2024. Data on cancer incidence and mortality trends were obtained from the Surveillance, Epidemiology, and End Results (SEER) program and National Centre for Health Statistics in the US and cancer registry reports of the National Cancer Center (NCC) of China. Data from the Global Burden of Disease study (GBD) and a decomposition approach were used to estimate the contributions of four determinants to the change in cancer deaths. RESULTS: In 2024, there are an estimated 3,246,625 and 2,510,597 new cancer cases and 1,699,066 and 640,038 cancer deaths in China and the US, respectively. The highest estimated cancer cases are lung cancer in China and breast cancer in the US. The age-standardized incidence rates of lung and colorectal cancer in the US, and stomach, liver, and esophageal cancer in China have decreased, but the incidence rates of liver cancer in the US and colorectal cancer, prostate cancer in men, and cervical cancer in women in China have increased. Increases in the adult population size and population aging are main reasons for the increase in cancer deaths; case fatality rates are a main reason for the decrease in cancer deaths in both countries. CONCLUSIONS China has made progress in cancer control but lags the US. Considering the transformation in China's pattern of cancers epidemiology, it is imperative to develop stronger policies by adopting the cancer prevention and control strategies used in the US to address population aging and curb growing cancer trends.
Humans ; China/epidemiology* ; United States/epidemiology* ; Male ; Neoplasms/mortality* ; Female ; Incidence ; SEER Program ; Middle Aged ; Adult ; Aged ; Lung Neoplasms/mortality*

This study aims to explore optimized teaching mode of cancer epidemiology for undergraduates, and provide scientific ideas and basis for improving teaching quality. Non-randomized concurrent control study was used. Undergraduates, enrolled in 2018, from the department of preventive medicine in A and B medical universities were selected as research objects. Traditional teaching mode was used for cancer epidemiology course in A medical university, and innovative teaching mode named "one core, four dimensions" was adopted in B medical university. After the course, questionnaire method was used to investigate self-cognition of students, teaching satisfaction and class preparation time of teachers in B Medical University. The post-class test method was used to compare the students′ grades of cancer epidemiology in the two universities. The results indicated that among the 58 students of B medical university, 94.83% (55/58) students were familiar with common types of epidemiological studies and 86.21% (50/58) mastered the evaluation indicators of screening research. Among the nine teaching faculties from B medical university, seven reported that the new teaching plan helped students to learn frontier knowledge of cancer epidemiology, and eight reported the new teaching model was conducive to the interaction between teachers and students. The text score of students in B medical university was 50.34±4.90, significantly higher than that in A medical university (46.21±4.91, t=5.20, P<0.001). The optimized teaching mode of cancer epidemiology is highly praised by students and teachers, which has the potential to improve students′ grasp of cancer epidemiology, the ability to combine theory with practice, and the teaching effect of cancer epidemiology.

This study aims to explore optimized teaching mode of cancer epidemiology for undergraduates, and provide scientific ideas and basis for improving teaching quality. Non-randomized concurrent control study was used. Undergraduates, enrolled in 2018, from the department of preventive medicine in A and B medical universities were selected as research objects. Traditional teaching mode was used for cancer epidemiology course in A medical university, and innovative teaching mode named "one core, four dimensions" was adopted in B medical university. After the course, questionnaire method was used to investigate self-cognition of students, teaching satisfaction and class preparation time of teachers in B Medical University. The post-class test method was used to compare the students′ grades of cancer epidemiology in the two universities. The results indicated that among the 58 students of B medical university, 94.83% (55/58) students were familiar with common types of epidemiological studies and 86.21% (50/58) mastered the evaluation indicators of screening research. Among the nine teaching faculties from B medical university, seven reported that the new teaching plan helped students to learn frontier knowledge of cancer epidemiology, and eight reported the new teaching model was conducive to the interaction between teachers and students. The text score of students in B medical university was 50.34±4.90, significantly higher than that in A medical university (46.21±4.91, t=5.20, P<0.001). The optimized teaching mode of cancer epidemiology is highly praised by students and teachers, which has the potential to improve students′ grasp of cancer epidemiology, the ability to combine theory with practice, and the teaching effect of cancer epidemiology.

Plant fungal pathogens secrete numerous proteins into the apoplast at the plant-fungus contact sites to facilitate colonization.However,only a few secretory proteins were functionally characterized in Magnaporthe oryzae,the fungal pathogen causing rice blast disease worldwide.Asparagine-linked glycosylation 3(Alg3)is an a-l,3-mannosyltransferase functioning in the N-glycan synthesis of N-glycosylated secretory proteins.Fungal pathogenicity and cell wall integrity are impaired in Aalg3 mutants,but the secreted proteins affected in Aalg3 mutants are largely unknown.In this study,we compared the secretomes of the wild-type strain and the Aalg3 mutant and identified 51 proteins that require Alg3 for proper secretion.These proteins were predicted to be involved in metabolic processes,interspecies interactions,cell wall organization,and response to chemicals.Nine proteins were selected for further validation.We found that these proteins were localized at the apoplastic region surrounding the fungal infection hyphae.Moreover,the N-glycosylation of these proteins was significantly changed in the Aalg3 mutant,leading to the decreased protein secretion and abnormal protein localization.Furthermore,we tested the biological functions of two genes,INV1(encoding invertase 1,a secreted invertase)and AMCase(encoding acid mammalian chinitase,a secreted chitinase).The fungal virulence was significantly reduced,and the cell wall integrity was altered in the Ainv1 and Aamcase mutant strains.Moreover,the N-glycosylation was essential for the function and secretion of AMCase.Taken together,our study provides new insight into the role of N-glycosylated secretory proteins in fungal virulence and cell wall integrity.