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 explore the perioperative safety of video-assisted thoracic surgery (VATS) in Day Care Unit and the risk factors for delayed discharge under centralized management model. Methods The patients with VATS managed by the Day Care Unit of the Drum Tower Hospital Affiliated to Nanjing University Medical School in 2021 were retrospectively collected. The patients’ postoperative data and risk factors for delayed discharge were analyzed. Results A total of 383 patients were enrolled, including 179 males and 204 females with an average age of 46.09±14.82 years. Eleven (2.87%) patients developed grade 3-4 postoperative complications during the hospitalization. Eighteen (4.70%) patients visited unscheduled outpatient clinic within 7 days, and 6 (1.57%) patients were re-hospitalized within 30 days after discharge. The remaining patients had no significant adverse events during the 30-day follow-up. The average length of hospital stay was 2.27±0.35 d. The length of hospital stay was over 48 h in 48 (12.53%) patients. The independent risk factor for delayed discharge was lobectomy or combined resection (OR=3.015, 95%CI 1.174-7.745, P=0.022). Conclusion VATS can be safely conducted under the centralized management in Day Care Unit. The risk factor for delayed discharge is the extent of surgical resection.

Neuroplastin 65(NP65) is a glycoprotein class with selective expression in neurons. It is extensively expressed in the synaptic membrane of the central nervous system, and plays a fundamental role in cell adhesion and intercellular communication. In comparison to other cell adhesion molecules, the discovery of NP65 is relatively late and researches about this molecule are still in development. Further exploration and study of the pathophysiological mechanism involved in NP65 are needed. It has been confirmed that NP65 plays a pivotal role in neural activities, including regulation of synaptic formation and maintenance, modulation of synaptic plasticity, facilitation of neuronal development, and contribution to the pathogenesis of various diseases. Thus, NP65 could potentially serve as a crucial target for modulating the growth and operation of the nervous system. This paper provides a comprehensive review of the structure, distribution, function, and involvement in both physiological and pathological processes of NP65. Additionally, the future research direction for NP65 is proposed, with the aim of enhancing our understanding of its function, revealing its mechanism of action in diseases, and providing a theoretical basis for the development of related clinical applications.

Objective To determine risk factors of postoperative pulmonary complications within 1 month in patients undergoing thoracic surgery in Day Care Unit.Methods The total of 200 patients routinely scheduled for VATS under centralized management were enrolled in this study.On the postoperative day 1,lung ultrasound(LUS)was conducted by one physician in the ward.The patients received at least once Chest X-ray or CT in outpatient department within 30 days after discharge.The composite of out-of-hospital PPCs,and the value of LUSS in predicting the PPCs was appraised.Furthermore,we identified the perioperative risk factors associated with PPCs in VATS patients.Results Of 200 recruited VATS patients eligible in the Nanjing Drum Tower Hospital,188 participants received LUS examination and finally completed the 30 days follow-up.Of whom,68 patients developed the varied types of PPCs.Multivariable Logistic regression analysis indicated that comorbidity of immune system disease(P = 0.021),lobar resection(P = 0.031)and the postoperative 24 hours LUSS(P = 0.002)were independent risk factors for PPCs within 30 days after VATS.Conclusion Comorbidity of immune system disease,lobar resection and the postoperative 24 h LUSS were independent risk factors for PPCs within 30 days after VATS.

Chronic pain patients are often accompanied with anxiety disorder, which promote the development of each other's disease process to a certain extent and seriously affect the quality of life of patients.However, the mechanism regulating the comorbidity between the two has not been clarified.Synaptic remodeling is the alteration of synaptic structure and function, which affects the transmission of signals between neurons.Synaptic remodeling is a hot topic in the field of chronic pain and anxiety disorders, but only few studies have explored its pathological changes in chronic pain and anxiety disorders.By summarizing the relevant researches in recent years, the occurrence of chronic pain co-anxiety disorder is closely related to changes in synaptic structure, synaptic transmission efficiency and synaptic function in brain regions.Synaptic remodeling could lead to the decline of centra pain regulation ability and aggravate the progression of chronic pain accompanied by anxiety disorder through ionic amino acid receptors, neuronal transmission and interactions between neurons and glial cells.Understanding the latest research progress of the co-morbidity mechanism of chronic pain and anxiety disorder is helpful to provide theoretical basis and potential new targets for its treatment.

The incidence of emotion disability-related diseases in adolescents is increasing year by year, causing great harm to their physical and mental health, even affecting them until adulthood. However, the mechanism of this has not been fully clarified. The default mode network is a brain network composed of brain regions that are still active in the resting state. DMN is a hot pot in the field of resting state brain function research, but few studies have focused on its pathological changes in the adolescents with emotion disability-related diseases. In recent years, a number of articles related to adolescent emotion disorders have provided clues for understanding the characteristics and potential mechanisms of adolescent emotion disorders from the perspective of imaging. This paper summarized the related research over the years and found that the occurrence of emotion disorders is closely related to the activation of the default mode network brain regions, cortical thickness, gray matter volume or density, and changes in functional connections between brain areas.Some changes in brain structure and function can be used as predictive factors. In this paper, by summarizing the changes in brain imaging of these emotion disorders, we hope to explore new neuroimaging landmark changes, which can provide theoretical basis for the prevention, diagnosis and treatment of emotion disorders related diseases in adolescents.

Objective: To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) combined with donepezil on the cognition of persons with post-stroke cognitive impairment (PSCI) and their ability to perform activities of daily living (ADL). Methods: A total of 106 PSCI patients were randomly divided into an observation group and a control group using a random number table. Those in the observation group received 10Hz rTMS (5 seconds on and 25 seconds off for 20 minutes daily) and donepezil daily, 5 days per week for 4 weeks, while those in the control group were provided with donepezil but only sham rTMS on the same schedule. Before and after 4 weeks of treatment, the Montreal cognitive assessment scale (MoCA), the Rivermead behavior memory test (RBMT) and the modified Barthel index (MBI) were used to evaluate the subjects′ cognitive functioning, memory capacity and ADL ability. The latency and amplitude of auditory event-related potential P300 were also assessed using a myoelectric evoked potential apparatus. Results: After the treatment, improvement was observed in all the measurements of both groups. After the treatment, the average MoCA, RBMT and MBI scores, as well as the latency and amplitude of P300 in the observation group were all significantly better than among the control group. Conclusions rTMS can supplement donepezil′s ability to improve the cognition and ADL ability of persons with PSCI. Such therapy is worthy of clinical promotion and application.

This study was a single-center large-sample case-control study.Data of 1 106 elderly patients who underwent unilateral total hip arthroplasty from June 2013 to May 2019 were collected, including items such as patient′s baseline characteristics, comorbidities, perioperative medication, intraoperative blood pressure, and postoperative outcomes.Patients were divided into postoperative nausea and vomiting(PONV)group and non-PONV group according to whether nausea and vomiting occurred within 24 h after operation.Logistic regression analysis was used to determine the risk factors for PONV.The incidence of PONV was 11.03%.Female, intraoperative use of dezocine, and intraoperative hypotension(duration>3 min or cumulative time>6 min)are independent risk factors for PONV, while femoral neck fractures and intraoperative use of dexamethasone are protective factors.

Objective To evaluate the influencing factors and early recovery quality in elderly patients with gastrointestinal tumor resection by the quality of recovery-40 questionnaire (QoR-40 questionnaire). Methods One hundred and forty- two elderly patients who had underwent gastrointestinal tumor resection from February to June 2017 were selected. The patients were over 65 years old. Their body mass index was (22.98 ± 3.20) kg/m2, and American Society of Anesthesilogists (ASA) wasⅡorⅢgrade. The patients were assessed with QoR-40 questionnaire on the first and second day after operation, and the factors affecting the total score of QoR-40 questionnaire on the first and second day after operation were analyzed. Results Compared with those on the first day after operation, the scores of emotional status, physical comfort, psychological support, physical independence, pain and total score of QoR-40 questionnaire on the second day after operation were significantly higher: 42 (39, 43) scores vs. 40 (38, 42) scores, 53 (52, 54) scores vs. 52 (50, 53) scores, 35 (35, 35) scores vs. 35 (34, 35) scores, 15 (13, 15) scores vs. 14 (12, 15) scores, 34 (33, 35) scores vs. 33 (32, 34) scores and 178 (173, 182) scores vs. 174 (169, 177) scores, and there were statistical differences (P<0.01). On the first day after operation, the total score of the QoR-40 questionnaire was related with the type of operation (P<0.05), and it was not related with age, sex and anesthesia (P>0.05);on the second day after operation, the total score of QoR-40 questionnaire was related with age and operation type (P<0.05), and it was not related with sex and anesthesia (P > 0.05). Conclusions The early postoperative period score of QoR-40 questionnaire in patients with colorectal tumor resection and age less than 70 years old is higher, and the recovery quality after operation is relatively good, suggesting that the operation type and age may be an important factor affecting the early recovery quality of the elderly patients with gastrointestinal tumor resection.

Capillary electrophoresis-based STR genotyping is accepted as the gold standard for human individual identification. Next generation sequencing (NGS) allows for the full resolution of STR base composition, and has the potential to be widely used in the field of forensics. Compared with length polymorphism, STR sequencing could provide more information, and quantitatively calculating the forensic parameters is necessary. In this paper, we established simple models for length-based and sequence-based STRs, and calculated the forensic parameters for both models. The results showed that for a single STR locus, compared with length polymorphism, STR sequence polymorphism could provide higher power of discrimination and power of exclusion, indicating sequence-based STR marker have stronger ability for identifying unrelated individuals and exclude non biological father. By combining 15 non-linkage loci for forensic DNA analysis, the cumulative matching probability values for length-based and sequence-based STR models are at 10-18and 10-26levels, respectively. Only 10 non-linkage sequence-based STR is required to reach a cumulative matching probability of as high as 15 length-based STR loci. It is hoped that these simulated models and calculations can provide a reference for the forensic application of NGS-based STR genotyping.