Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective A cross-sectional survey on the postoperative home care status and barriers was conducted among elderly patients with osteoporotic fractures nationwide,in order to provide a basis for promoting the improvement of standardized home care for elderly patients with osteoporotic fractures.Methods From October to November 2023,a survey on the current situation and barriers of home environment protection was conducted among elderly patients with osteoporotic fractures in the orthopedic wards of 594 hospitals across 31 provinces(autonomous regions/municipalities directly under the central government)using a convenience sampling method.Results A total of 14,349 questionnaires were distributed,and 12,496 valid questionnaires were collected,resulting in an effective response rate of 87.09％.Among the patients,5,502 cases(44.03％)had implemented home-based prevention and treatment of osteoporosis before the fracture.2 095(16.77％)of the patients experienced a subsequent fracture,of which 65.11％of the patients who experienced a subsequent fracture received medication intervention after the initial fracture,while 19.86％of the patients who experienced a subsequent fracture did not comply with the treatment for osteoporosis after the initial fracture.Additionally,77.66％(n=1 627/2 095)of the patients received community medical services after the initial fracture.Barriers to care factors in the home environment after fracture from the patient's perspective presented the complexity of the social-ecological system model in 6 dimensions at 2 levels:micro(basic personal situation,physiological factors,psychological factors,and behavioural factors),and meso(social support factors,and healthcare worker factors).Conclusion In the vast majority of elderly patients in China,before osteoporotic fracture,home-based measures to prevent osteoporosis have not been adequately implemented;after the initial osteoporotic fracture,the pathway of re-fracture prevention and management in the patient's home environment is not yet complete and its popularity needs to be improved;the barriers to home care faced by elderly patients with osteoporotic fracture are complex.It is recommended to promote effective linkages among hospitals,community health centres and families to strengthen the closed-loop management of re-fracture prevention and management.

Objective:To investigate the impact of early invasive arterial blood pressure (IBP) monitoring on survival and neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR).Methods:This retrospective cohort study analyzed 44 OHCA patients receiving ECPR between January 2021 and January 2023. Patients were divided into: Early intervention group : IBP established within 3 min of ECMO initiation; Late intervention group : IBP established after ICU admission. Baseline characteristics, ECMO parameters, and clinical outcomes were compared. Multivariable logistic regression (adjusted for age, initial rhythm, etc.) and Spearman's correlation were used.Results:This study included a total of 44 patients treated with OHCA and ECPR, divided into an early intervention group of 23 cases and a late intervention group of 21 cases. The early intervention group showed significantly higher: Survival to discharge (43.5% vs. 9.5%, P<0.05), Good neurological recovery (CPC 1-2: 34.8% vs. 9.5%, P<0.05).Early intervention independently predicted survival (adjusted OR=18.84, 95% CI:1.97-179.98, P=0.01). Stratified analysis by pH (cutoff 7.0) demonstrated consistent benefits in both pH>7.0 ( aOR=0.392, 95% CI:0.106-0.678) and pH≤7.0 subgroups ( aOR=0.385, 95% CI: 0.075-0.695; interaction P=0.183). Early IBP positively correlated with CPC scores ( ρ=0.40, P=0.007). Conclusions:Early IBP monitoring significantly improves survival and neurological outcomes in OHCA-ECPR patients, supporting its integration into standardized protocols.

Ivonescimab is a humanized bispecific antibody targeting human vascular endothelial growth factor-A(VEGF-A)and programmed death protein-1(PD-1).It was approved by National Medi-cal Products Administration on May 24th,2024,and can be used in combination with pemetrexed and carboplatin for locally advanced or positive EG-FR gene mutation after treatment with epidermal growth factor receptor(EGFR)tyrosine kinase inhib-itor.This paper mainly introduces the research progress of the world's first PD-1/VEGF bispecific antibody ivonescimab,and summarizes the mecha-nism of action,pharmacokinetics,phase Ⅰ-Ⅲ clinical trials and drug safety.

Objective:To develop a Knowledge-Attitude-Practice (KAP) Scale for Dietary Management During Hemodialysis and to test its reliability and validity.Methods:Based on the KAP theoretical framework, an initial version of the scale was developed through a literature review and expert consultations. A convenience sampling method was used to recruit hemodialysis patients from four hospitals in Suzhou in March 2024. Questionnaire item analysis and reliability and validity tests were conducted.Results:A total of 460 questionnaires were distributed and 438 valid responses were collected, with an effective response rate of 95.22%. The final scale included three dimensions (knowledge, attitude, and practice) with 34 items. Content validity at the scale level was 0.910, and the item level ranged from 0.800 to 1.000. Exploratory factor analysis extracted three common factors, with a cumulative variance contribution rate of 74.520%. Confirmatory factor analysis showed a good model fit. The total Cronbach's α coefficient of the scale was 0.971, and the Cronbach's αcoefficients for the three dimensions were 0.963, 0.933, and 0.934, respectively. The test-retest reliability coefficient was 0.839.Conclusions:The Knowledge-Attitude-Practice Scale for Dietary Management During Hemodialysis demonstrates good reliability and validity, making it a valuable tool for assessing the KAP level of dietary management in hemodialysis patients.

Objective:To investigate the predictive value and risk relationship of preoperative serum high-density lipoprotein cholesterol (HDL-C), milk fat globule-epidermal growth factor 8 (MFG-E8), and 24-hour postoperative lactate load in acute kidney injury (AKI) following cardiac valve surgery.Methods:A retrospective analysis was conducted on 60 patients who underwent cardiac valve surgery at the Cardiovascular Surgery Department of Yan′an University Affiliated Hospital from January 2020 to December 2023 and developed postoperative AKI (AKI group). Another 60 patients who underwent the same surgery during the same period but did not develop AKI were selected as the control group. Preoperative and postoperative laboratory results and general clinical data were compared between the two groups. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of preoperative serum HDL-C, MFG-E8, and 24-hour postoperative lactate load for AKI. A logistic regression model was employed to analyze the risk relationship between these three indicators and AKI.Results:The AKI group had significantly lower preoperative serum HDL-C [(1.06±0.13)mmol/L] and MFG-E8 [(413.6±73.0)ng/L] compared with the control group [HDL-C (1.15±0.18)mmol/L, MFG-E8 (461.8±85.7)ng/L], while the 24-hour postoperative lactate load [(155.8±29.0)mmol/L] was significantly higher than that of the control group [(128.1±25.0)mmol/L] (all P<0.05). The area under the ROC curve (AUC) values for preoperative HDL-C, MFG-E8, and 24-hour postoperative lactate load in predicting AKI following cardiac valve surgery were 0.642, 0.611, and 0.818, respectively. Logistic regression analysis revealed that decreased preoperative HDL-C ( OR=0.822), decreased preoperative MFG-E8 ( OR=0.674), increased 24-hour postoperative lactate load ( OR=1.781), prolonged cardiopulmonary bypass time ( OR=1.848), prolonged aortic cross-clamp time ( OR=1.470), elevated preoperative serum creatinine (Scr) ( OR=1.941), and increased 24-hour postoperative fluid balance ( OR=1.775) were independent risk factors for AKI following cardiac valve surgery (all P<0.05). Conclusions:Patients who developed AKI after cardiac valve surgery had lower preoperative serum HDL-C and MFG-E8 levels and higher 24-hour postoperativelactate load. Among these, the 24-hour postoperative lactate load demonstrated significant predictive value for AKI, and all three indicators were closely associated with AKI occurrence.

Objective:To investigate the predictive value and risk relationship of preoperative serum high-density lipoprotein cholesterol (HDL-C), milk fat globule-epidermal growth factor 8 (MFG-E8), and 24-hour postoperative lactate load in acute kidney injury (AKI) following cardiac valve surgery.Methods:A retrospective analysis was conducted on 60 patients who underwent cardiac valve surgery at the Cardiovascular Surgery Department of Yan′an University Affiliated Hospital from January 2020 to December 2023 and developed postoperative AKI (AKI group). Another 60 patients who underwent the same surgery during the same period but did not develop AKI were selected as the control group. Preoperative and postoperative laboratory results and general clinical data were compared between the two groups. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of preoperative serum HDL-C, MFG-E8, and 24-hour postoperative lactate load for AKI. A logistic regression model was employed to analyze the risk relationship between these three indicators and AKI.Results:The AKI group had significantly lower preoperative serum HDL-C [(1.06±0.13)mmol/L] and MFG-E8 [(413.6±73.0)ng/L] compared with the control group [HDL-C (1.15±0.18)mmol/L, MFG-E8 (461.8±85.7)ng/L], while the 24-hour postoperative lactate load [(155.8±29.0)mmol/L] was significantly higher than that of the control group [(128.1±25.0)mmol/L] (all P<0.05). The area under the ROC curve (AUC) values for preoperative HDL-C, MFG-E8, and 24-hour postoperative lactate load in predicting AKI following cardiac valve surgery were 0.642, 0.611, and 0.818, respectively. Logistic regression analysis revealed that decreased preoperative HDL-C ( OR=0.822), decreased preoperative MFG-E8 ( OR=0.674), increased 24-hour postoperative lactate load ( OR=1.781), prolonged cardiopulmonary bypass time ( OR=1.848), prolonged aortic cross-clamp time ( OR=1.470), elevated preoperative serum creatinine (Scr) ( OR=1.941), and increased 24-hour postoperative fluid balance ( OR=1.775) were independent risk factors for AKI following cardiac valve surgery (all P<0.05). Conclusions:Patients who developed AKI after cardiac valve surgery had lower preoperative serum HDL-C and MFG-E8 levels and higher 24-hour postoperativelactate load. Among these, the 24-hour postoperative lactate load demonstrated significant predictive value for AKI, and all three indicators were closely associated with AKI occurrence.

Objective A cross-sectional survey on the postoperative home care status and barriers was conducted among elderly patients with osteoporotic fractures nationwide,in order to provide a basis for promoting the improvement of standardized home care for elderly patients with osteoporotic fractures.Methods From October to November 2023,a survey on the current situation and barriers of home environment protection was conducted among elderly patients with osteoporotic fractures in the orthopedic wards of 594 hospitals across 31 provinces(autonomous regions/municipalities directly under the central government)using a convenience sampling method.Results A total of 14,349 questionnaires were distributed,and 12,496 valid questionnaires were collected,resulting in an effective response rate of 87.09％.Among the patients,5,502 cases(44.03％)had implemented home-based prevention and treatment of osteoporosis before the fracture.2 095(16.77％)of the patients experienced a subsequent fracture,of which 65.11％of the patients who experienced a subsequent fracture received medication intervention after the initial fracture,while 19.86％of the patients who experienced a subsequent fracture did not comply with the treatment for osteoporosis after the initial fracture.Additionally,77.66％(n=1 627/2 095)of the patients received community medical services after the initial fracture.Barriers to care factors in the home environment after fracture from the patient's perspective presented the complexity of the social-ecological system model in 6 dimensions at 2 levels:micro(basic personal situation,physiological factors,psychological factors,and behavioural factors),and meso(social support factors,and healthcare worker factors).Conclusion In the vast majority of elderly patients in China,before osteoporotic fracture,home-based measures to prevent osteoporosis have not been adequately implemented;after the initial osteoporotic fracture,the pathway of re-fracture prevention and management in the patient's home environment is not yet complete and its popularity needs to be improved;the barriers to home care faced by elderly patients with osteoporotic fracture are complex.It is recommended to promote effective linkages among hospitals,community health centres and families to strengthen the closed-loop management of re-fracture prevention and management.

Ivonescimab is a humanized bispecific antibody targeting human vascular endothelial growth factor-A(VEGF-A)and programmed death protein-1(PD-1).It was approved by National Medi-cal Products Administration on May 24th,2024,and can be used in combination with pemetrexed and carboplatin for locally advanced or positive EG-FR gene mutation after treatment with epidermal growth factor receptor(EGFR)tyrosine kinase inhib-itor.This paper mainly introduces the research progress of the world's first PD-1/VEGF bispecific antibody ivonescimab,and summarizes the mecha-nism of action,pharmacokinetics,phase Ⅰ-Ⅲ clinical trials and drug safety.

Objective:To develop a Knowledge-Attitude-Practice (KAP) Scale for Dietary Management During Hemodialysis and to test its reliability and validity.Methods:Based on the KAP theoretical framework, an initial version of the scale was developed through a literature review and expert consultations. A convenience sampling method was used to recruit hemodialysis patients from four hospitals in Suzhou in March 2024. Questionnaire item analysis and reliability and validity tests were conducted.Results:A total of 460 questionnaires were distributed and 438 valid responses were collected, with an effective response rate of 95.22%. The final scale included three dimensions (knowledge, attitude, and practice) with 34 items. Content validity at the scale level was 0.910, and the item level ranged from 0.800 to 1.000. Exploratory factor analysis extracted three common factors, with a cumulative variance contribution rate of 74.520%. Confirmatory factor analysis showed a good model fit. The total Cronbach's α coefficient of the scale was 0.971, and the Cronbach's αcoefficients for the three dimensions were 0.963, 0.933, and 0.934, respectively. The test-retest reliability coefficient was 0.839.Conclusions:The Knowledge-Attitude-Practice Scale for Dietary Management During Hemodialysis demonstrates good reliability and validity, making it a valuable tool for assessing the KAP level of dietary management in hemodialysis patients.