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::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.

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.

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.

Objective    To detect the expression of PITX2 and KCNQ1 in the left atrial appendage of patients with atrial fibrillation after modified mini-maze procedure, and to detect the clinical risk factors of different types of atrial fibrillation. Methods    We collected left atrial appendage tissue of 59 atrial fibrillation patients who received modified mini-maze procedure and left atrial appendectomy from February 2017 to August 2018. The expression levels of PITX2 and KCNQ1 of left atrial appendage tissue were quantitatively analyzed by western blotting assay between paroxysmal attial fibrillation and persistent atrial fibrillation groups. The correlation between protein expression and prognosis after surgery was also analyzed based on clinical data. Results    Binary-logistic regression analysis showed that KCNQ1 expression level was an independent risk factor for the progression from paroxysmal atrial fibrillation to persistent atrial fibrillation. Receiver operating characteristic (ROC) curve confirmed that KCNQ1 expression level (the ratio of KCNQ1 to actin in the analysis) was 0.60, which was the best cut-off point for the progression of paroxysmal atrial fibrillation to persistent atrial fibrillation. Conclusion    High expression of KCNQ1 in left atrial appendage is a risk factor for progression from paroxysmal atrial fibrillation to persistent atrial fibrillation.

Objective To summarize the treatment decision-making strategy and its long-term efficacy for advanced elderly patients with severe valvular heart disease and clear indications for surgery.Methods Clinical data of 196 patients aged 75 years and older firmly diagnosed as severe valvular heart diseases were retrospectively analyzed.The patients were divided into the surgical group (a mean age of 77.4±2.0 years,n=126)and the conservative group(a mean age of 80.5±5.0 years,n =70).Factors affecting therapeutic decision-making were analyzed,and the differences in a long-term survival were compared between the two groups.Results The most common reason for choosing conservative treatment was the recommendation of the doctor giving a preliminary diagnosis and worrying about the high-risk surgery for the patients(62.9％,44/70).Only 26(37.1％)patients in the conservative group were evaluated by cardiac surgeons,among whom 12 (17.1％)patients were considered to have surgical contraindications,and 14 (20.0％) patients themselves or their family members chose conservative treatment for the fear of surgical risks.Patients in the operation group were mainly from the outpatient department of cardiac surgery,and only 8 (6.3 ％)cases were referred from department of internal medicine.Logistic regression analysis showed that female,chronic renal insufficiency,advanced age,pneumonia and emergency hospital admissions were independent predictors for the conservative option(P ＜0.01),while patients with isolated aortic valve disease tended to receive surgical treatment.Overall 5-year survival was higher in the surgical group than in the conservative group (76.4％ vs.39.9％,P ＜ 0.01).Cox regression analysis disclosed that the conservative treatment option was the single risk factor for long-term survival in all series.Conclusions Many factors affect the process of therapeutic decision-making for patients with severe valvular heart diseases,and a multidisciplinary collaboration is the best way for the optimal treatment strategy for those patients.

Objective To investigate the effects of Qishen Erlian Decoction on serum MMP-1 and TIMP-1 levels in thioacetamide (TAA) induced liver fibrosis rats; To discuss its mechanism of action. Methods Liver fibrosis model was created by the TAA gavage method. 120 SD male rats were randomly assigned to control group, model group, colchicine group, Qishen Erlian Decoction low-, medium- and high-dose group (20 in each group). Each medication group was given relevant medicine for gavage. Control group and model group were given the same amount of normal saline for gavage, once a day for 5 weeks. HE staining and Masson trichrome staining were used to observe the pathological changes in liver tissue and liver tissue damage. Biochemistry, radioimmunoassay, and ELISA were used to detect the serum liver function, hepatic fibrosis index, MMP-1 and TIMP-1 levels. Results Compared with the model group, serum ALT, AST, TBIL, γ-GGT, HA, LN, Ⅳ-C and PCⅢ levels, MMP-1 and the ratio of MMP-1/TIMP-1 increased significantly and level of TIMP-1 decreased significantly in Qishen Erlian Decoction groups, with statistical significance (P<0.05, P<0.01). And there is a certain dose-effect relationship, with Qishen Erlian Decoction high-dose group the best effect. Conclusion Qishen Erlian Decoction can improve the liver function and liver fibrosis indexes, regulate the level of MMP-1 and TIMP-1, and prevent the progression of liver fibrosis.