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: To develop a comprehensive health economics evaluation model for HIV blood screening using Markov modeling, so as to evaluate the quality-of-life adjustment years (QALYs) gained by transfusion recipients after implementation of blood HIV screening. Methods: Shenzhen Blood Center was selected as the validation case for model development. Based on historical HIV screening data of Shenzhen Blood Center and published literature, the health economics evaluation of donor HIV screening was performed using cost-utility analysis. The single factor sensitivity analysis was performed on parameters in the model. Results: 3.09 QALYs were gained for each transfusion recipient prevented from HIV infection. During 2020-2023, donor HIV screening at Shenzhen Blood Center saved 506.76 QALYs, and each QALY saved 182 900 yuan. Conclusion: From the perspective of long-term benefit of transfusion recipients, HIV screening of blood donors demonstrates high health and economic value.

Objective: To develop a comprehensive health economics evaluation model for HIV blood screening using Markov modeling, so as to evaluate the quality-of-life adjustment years (QALYs) gained by transfusion recipients after implementation of blood HIV screening. Methods: Shenzhen Blood Center was selected as the validation case for model development. Based on historical HIV screening data of Shenzhen Blood Center and published literature, the health economics evaluation of donor HIV screening was performed using cost-utility analysis. The single factor sensitivity analysis was performed on parameters in the model. Results: 3.09 QALYs were gained for each transfusion recipient prevented from HIV infection. During 2020-2023, donor HIV screening at Shenzhen Blood Center saved 506.76 QALYs, and each QALY saved 182 900 yuan. Conclusion: From the perspective of long-term benefit of transfusion recipients, HIV screening of blood donors demonstrates high health and economic value.

Objective To summarise the best evidence on non-pharmacological management in children and to provide evidence-based guidelines for clinical practice.Methods With the 6S evidence pyramid model,a comprehensive and systematic search across multiple databases was conducted,including UpToDate,BMJ Best Practice,Joanna Briggs Institute of Australia's Centre for Evidence-based Health Care Database(JBI),National Guideline Clearing-house(NGC),Guidelines International Network(GIN),The National Institute for Health and Care Excellence(NICE)website,Scottish Intercollegiate Guidelines Network(SIGN),American Dental Association,Canadian Dental Association,Cochrane Library,CINAHL,Embase,PubMed,SinoMed,CNKI and Wanfang Data.The search focused on literature pertaining to the improvement of non-pharmacological strategies for compliance with paediatric oral treatment,encompassing clinical decisions,evidence summaries,clinical guidelines,systematic reviews,expert consensus,best practices,and randomised controlled trials.The literature search encompassed all available publications from the inception of databases up to 5th November,2023.A quality assessment of the literature was independently conducted by four researchers trained by evidence-based nursing courses,while evidence extraction and summarisation were handled by two researchers.Results A total of 16 papers were included,comprising 2 clinical decisions,2 evidence summaries,3 guidelines,5 systematic evaluations,1 best practice,2 expert consensus and 1 randomised controlled trial.Nineteen pieces of evidence were extracted and classified into six categories:outpatient setting,assessment and management of children,pre-treatment non-pharmacological management,in-treatment non-pharmacological management,post-treatment non-pharmacological management and training and assessment.Conclusion This study summarises the best evidences for non-pharmacological management aiming to improve the oral treatment compliance in children.Healthcare providers can facilitate the translation of this evidence into clinical practice by considering the specific clinical context as well as factors such as the age and psychological characteristics of children.

BACKGROUND:Poor prognosis of hip arthroplasty in patients with osteoporosis seriously affects the patients'quality of life.Accurately predicting the risk factors for poor prognosis of hip arthroplasty in patients with osteoporosis remains a major challenge for orthopedic surgeons.OBJECTIVE:To explore risk factors for poor prognosis after hip arthroplasty in patients with osteoporosis and construct a Nomogram prediction model.METHODS:A total of 192 patients with osteoporosis who underwent hip arthroplasty in Nanyang Second People's Hospital from July 2020 to June 2022 were selected as study subjects.Harris hip function scale was performed 6 months after operation.Patients with Harris score ≥ 80 were included in the good prognosis group(n=142),while patients with Harris score＜80 were included in the poor prognosis group(n=50).Clinical data of the two groups were collected and subjected to univariate analysis.Receiver operating characteristic curves were used to analyze the predictive value of the measures for poor prognosis after hip arthroplasty in patients with osteoporosis.Binary logistic regression was used to analyze the risk factors affecting poor prognosis after hip arthroplasty in patients with osteoporosis.The Nomogram prediction model for poor prognosis after hip arthroplasty in patients with osteoporosis was constructed.The calibration curve was internally validated and the concordance index was calculated,and the decision curve was evaluated for clinical predictive efficacy.RESULTS AND CONCLUSION:(1)The differences between the two groups were statistically significant in terms of age,body mass index,operative time,intraoperative bleeding,serum albumin,peripheral blood lymphocyte count,prognostic nutritional index,and complications(P＜0.05).(2)Area under the curve for age,body mass index,operative time,intraoperative bleeding,serum albumin,peripheral blood lymphocyte count,and prognostic nutritional index were 0.813,0.780,0.787,0.764,0.777,0.785,and 0.818.(3)Age,body mass index,intraoperative bleeding,and complications were risk factors for poor prognosis after hip arthroplasty in patients with osteoporosis.(4)The corrected,raw curve of the nomogram prediction model was close to the ideal curve with a concordance index of 0.851(0.815-0.886)and a good model fit,with a threshold of＞0.12 for the Nomogram prediction model to provide a net clinical benefit,and all net clinical benefits were higher than the independent predictors.(5)It is concluded that age,body mass index,intraoperative bleeding,and complications are risk factors affecting the poor prognosis of osteoporotic patients after hip arthroplasty.The Nomogram prediction model constructed based on this can help clinicians assess the prognosis of osteoporotic patients after hip arthroplasty,develop personalized interventions,improve prognosis,and enhance the quality of life.

Objective To summarise the best evidence on non-pharmacological management in children and to provide evidence-based guidelines for clinical practice.Methods With the 6S evidence pyramid model,a comprehensive and systematic search across multiple databases was conducted,including UpToDate,BMJ Best Practice,Joanna Briggs Institute of Australia's Centre for Evidence-based Health Care Database(JBI),National Guideline Clearing-house(NGC),Guidelines International Network(GIN),The National Institute for Health and Care Excellence(NICE)website,Scottish Intercollegiate Guidelines Network(SIGN),American Dental Association,Canadian Dental Association,Cochrane Library,CINAHL,Embase,PubMed,SinoMed,CNKI and Wanfang Data.The search focused on literature pertaining to the improvement of non-pharmacological strategies for compliance with paediatric oral treatment,encompassing clinical decisions,evidence summaries,clinical guidelines,systematic reviews,expert consensus,best practices,and randomised controlled trials.The literature search encompassed all available publications from the inception of databases up to 5th November,2023.A quality assessment of the literature was independently conducted by four researchers trained by evidence-based nursing courses,while evidence extraction and summarisation were handled by two researchers.Results A total of 16 papers were included,comprising 2 clinical decisions,2 evidence summaries,3 guidelines,5 systematic evaluations,1 best practice,2 expert consensus and 1 randomised controlled trial.Nineteen pieces of evidence were extracted and classified into six categories:outpatient setting,assessment and management of children,pre-treatment non-pharmacological management,in-treatment non-pharmacological management,post-treatment non-pharmacological management and training and assessment.Conclusion This study summarises the best evidences for non-pharmacological management aiming to improve the oral treatment compliance in children.Healthcare providers can facilitate the translation of this evidence into clinical practice by considering the specific clinical context as well as factors such as the age and psychological characteristics of children.

Objective:To analyze the clinical application of protocol biopsy (PB) during postoperative follow-up in recipients of allogeneic kidney transplantation.Methods:A prospective observational cohort study was conducted. Recipients who underwent allogeneic kidney transplantation at the Second Affiliated Hospital of Nanjing Medical University between January 2022 and September 2024 and received PB at 3 months (±1 week) and/or 12 months (±4 weeks) post-transplantation in the Department of Nephrology were enrolled. The implementation, complications, and pathological results of PB were summarized. The safety and diagnostic efficacy of PB were analyzed.Results:A total of 143 allogeneic kidney transplant recipients were included, and 200 PB procedures were performed. The overall implementation rate of protocol biopsy (PB) was 84.1% (143/170). Among them, 170 recipients completed 3-month follow-up, and 136 PBs were performed at 3 months (±1 week) post-transplantation, with an implementation rate of 80.0%. Seventy-nine recipients completed 12-month follow-up, and 64 PBs were performed at 12 months (±4 weeks), with an implementation rate of 81.0%. One major PB-related complication occurred (0.5%), presenting as gross hematuria and diagnosed as a transplant renal arteriovenous fistula. At 3 months post-transplantation, 58 biopsies (42.6%) showed pathological abnormalities, including rejection in 12 cases (8.8%), borderline changes in 18 cases (13.2%), BK virus nephropathy (BKVN) in 10 cases (7.4%), calcineurin inhibitor (CNI) nephrotoxicity in 13 cases (9.6%), and recurrent kidney disease in 5 cases (3.7%). At 12 months post-transplantation, 22 biopsies (34.4%) revealed pathological abnormalities, including rejection in 13 cases (20.3%), borderline changes in 4 cases (6.3%), BKVN in 3 cases (4.7%), CNI nephrotoxicity in 1 case (1.6%), and recurrent disease in 1 case (1.6%).Conclusions:Protocol kidney allograft biopsy after allogeneic kidney transplantation is highly safe and feasible in clinical practice. PB provides significant diagnostic value for the early detection of subclinical rejection and BKVN, thereby supporting its clinical utility in postoperative monitoring and management.

BACKGROUND:Poor prognosis of hip arthroplasty in patients with osteoporosis seriously affects the patients'quality of life.Accurately predicting the risk factors for poor prognosis of hip arthroplasty in patients with osteoporosis remains a major challenge for orthopedic surgeons.OBJECTIVE:To explore risk factors for poor prognosis after hip arthroplasty in patients with osteoporosis and construct a Nomogram prediction model.METHODS:A total of 192 patients with osteoporosis who underwent hip arthroplasty in Nanyang Second People's Hospital from July 2020 to June 2022 were selected as study subjects.Harris hip function scale was performed 6 months after operation.Patients with Harris score ≥ 80 were included in the good prognosis group(n=142),while patients with Harris score＜80 were included in the poor prognosis group(n=50).Clinical data of the two groups were collected and subjected to univariate analysis.Receiver operating characteristic curves were used to analyze the predictive value of the measures for poor prognosis after hip arthroplasty in patients with osteoporosis.Binary logistic regression was used to analyze the risk factors affecting poor prognosis after hip arthroplasty in patients with osteoporosis.The Nomogram prediction model for poor prognosis after hip arthroplasty in patients with osteoporosis was constructed.The calibration curve was internally validated and the concordance index was calculated,and the decision curve was evaluated for clinical predictive efficacy.RESULTS AND CONCLUSION:(1)The differences between the two groups were statistically significant in terms of age,body mass index,operative time,intraoperative bleeding,serum albumin,peripheral blood lymphocyte count,prognostic nutritional index,and complications(P＜0.05).(2)Area under the curve for age,body mass index,operative time,intraoperative bleeding,serum albumin,peripheral blood lymphocyte count,and prognostic nutritional index were 0.813,0.780,0.787,0.764,0.777,0.785,and 0.818.(3)Age,body mass index,intraoperative bleeding,and complications were risk factors for poor prognosis after hip arthroplasty in patients with osteoporosis.(4)The corrected,raw curve of the nomogram prediction model was close to the ideal curve with a concordance index of 0.851(0.815-0.886)and a good model fit,with a threshold of＞0.12 for the Nomogram prediction model to provide a net clinical benefit,and all net clinical benefits were higher than the independent predictors.(5)It is concluded that age,body mass index,intraoperative bleeding,and complications are risk factors affecting the poor prognosis of osteoporotic patients after hip arthroplasty.The Nomogram prediction model constructed based on this can help clinicians assess the prognosis of osteoporotic patients after hip arthroplasty,develop personalized interventions,improve prognosis,and enhance the quality of life.

Objective:To analyze the clinical application of protocol biopsy (PB) during postoperative follow-up in recipients of allogeneic kidney transplantation.Methods:A prospective observational cohort study was conducted. Recipients who underwent allogeneic kidney transplantation at the Second Affiliated Hospital of Nanjing Medical University between January 2022 and September 2024 and received PB at 3 months (±1 week) and/or 12 months (±4 weeks) post-transplantation in the Department of Nephrology were enrolled. The implementation, complications, and pathological results of PB were summarized. The safety and diagnostic efficacy of PB were analyzed.Results:A total of 143 allogeneic kidney transplant recipients were included, and 200 PB procedures were performed. The overall implementation rate of protocol biopsy (PB) was 84.1% (143/170). Among them, 170 recipients completed 3-month follow-up, and 136 PBs were performed at 3 months (±1 week) post-transplantation, with an implementation rate of 80.0%. Seventy-nine recipients completed 12-month follow-up, and 64 PBs were performed at 12 months (±4 weeks), with an implementation rate of 81.0%. One major PB-related complication occurred (0.5%), presenting as gross hematuria and diagnosed as a transplant renal arteriovenous fistula. At 3 months post-transplantation, 58 biopsies (42.6%) showed pathological abnormalities, including rejection in 12 cases (8.8%), borderline changes in 18 cases (13.2%), BK virus nephropathy (BKVN) in 10 cases (7.4%), calcineurin inhibitor (CNI) nephrotoxicity in 13 cases (9.6%), and recurrent kidney disease in 5 cases (3.7%). At 12 months post-transplantation, 22 biopsies (34.4%) revealed pathological abnormalities, including rejection in 13 cases (20.3%), borderline changes in 4 cases (6.3%), BKVN in 3 cases (4.7%), CNI nephrotoxicity in 1 case (1.6%), and recurrent disease in 1 case (1.6%).Conclusions:Protocol kidney allograft biopsy after allogeneic kidney transplantation is highly safe and feasible in clinical practice. PB provides significant diagnostic value for the early detection of subclinical rejection and BKVN, thereby supporting its clinical utility in postoperative monitoring and management.

【Objective】 To explore the the potential risks of antiretroviral therapy(ART) drugs on blood safety among blood donors in Shenzhen. 【Methods】 High pressure liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was used to measure ART drugs concentrations in the plasma of regular blood donors (negative control group, n=86) and anti-HIV positive individuals (experimental group, n=98, detected from approximately 440 000 blood donors during 2019—2023). The baseline plasma concentrations of ART drugs in the negative control group were clarified, and the impact of ART drugs on blood safety was analyzed. 【Results】 The baseline concentrations of ART drugs were not detected in 86 samples of negative control group. Four positive ART drugs samples were detected in 1∶2 pooled plasma samples of 98 anti-HIV positive blood donors plasma in the resolution test. The ART positive rate of anti-HIV positive donors was 4.08%, with tenofovir, lamivudine and efavirenz detected in three blood donors and lamivudine, lopinavir, ritonavir and zidovudine detected in one blood donor. 【Conclusion】 ART drugs were found among anti-HIV positive blood donors in Shenzhen. Additional research is needed to investigate the motivation of these specific donors, so as to ascertain the groups most susceptible to potential risks, and guarantee blood safety.