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

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.

Postoperative delirium(POD),a common surgical complication,refers to the acute and fluctuating disturbance in attention and awareness after surgery,which seriously affects the recovery and is one of the predictors of poor prognosis of patients.At present,preoperative anxiety is common in periopera-tive patients.As the independent risk factors for POD,preoperative anxiety plays an important role in the occurrence and development of POD.Taking active and reasonable intervention measures for patients with preoperative anxiety may effectively reduce the occurrence of POD.This paper reviews the effects of preoper-ative anxiety on POD,focusing on its mechanism and prevention methods,in order to explore the relation-ship between preoperative anxiety and POD,which might provide new ideas for the clinic.

Recent advancement in natural language processing (NLP) and medical imaging empowers the wide applicability of deep learning models. These developments have increased not only data understanding, but also knowledge of state-of-the-art architectures and their real-world potentials. Medical imaging researchers have recognized the limitations of only targeting images, as well as the importance of integrating multimodal inputs into medical image analysis. The lack of comprehensive surveys of the current literature, however, impedes the progress of this domain. Existing research perspectives, as well as the architectures, tasks, datasets, and performance measures examined in the present literature, are reviewed in this work, and we also provide a brief description of possible future directions in the field, aiming to provide researchers and healthcare professionals with a detailed summary of existing academic research and to provide rational insights to facilitate future research.
Humans ; Natural Language Processing ; Surveys and Questionnaires

Objective:To investigate the expression levels and clinical significance of collagen typeⅠ α1 chain (COL1A1) and collagen type Ⅰ α2 chain (COL1A2) in malignant pleural mesothelioma (MPM) tissues.Methods:In January 2020, MPM tissues and adjacent normal pleural tissues were collected from 26 MPM patients, and the expression levels of COL1A1 and COL1A2 genes in the tissues were determined by quantitative reverse transcription PCR, and the efficacy of both levels in diagnosing MPM was assessed using receiver operating characteristic (ROC) curves. The relationship between COL1A1 and COL1A2 gene expression and clinicopathological features was analyzed by the Cancer Genome Atlas (TCGA) database, and the relationship between the expression levels of both and overall survival (OS) and disease-free progression survival (DFS) of MPM patients was dynamically analyzed by gene expression profiling, and the factors affecting the prognosis of MPM patients were explored by Cox proportional risk regression model. The TIMER 2.0 platform was used to explore the relationship between COL1A1 and COL1A2 gene expression in MPM and tumor immune infiltrative cells.Results:Compared with normal pleural tissues, the expression of COL1A1 and COL1A2 genes was significantly increased in MPM tissues ( P<0.01) , and their expression was positively correlated ( P<0.001) . The ROC curves showed that the area under the curve for COL1A1 and COL1A2 expression levels diagnostic of MPM was 0.900 and 0.897, respectively. The expression of COL1A1 gene was correlated with tumor type in MPM patients ( P<0.05) , and COL1A2 gene expression was correlated with T stage in MPM patients ( P<0.05) . Both COL1A1 and COL1A2 gene expression were associated with OS in MPM patients (Logrank P<0.05) , but there was no significant correlation with DFS (Logrank P>0.05) . Cox multivariate analysis showed that patients with high COL1A1 and COL1A2 gene expression and biphasic mixed MPM had a higher risk of death ( P<0.05) . TIMER 2.0 platform analysis showed that COL1A1 and COL1A2 gene expression in MPM patients was positively correlated with macrophages, COL1A2 gene expression in MPM was negatively correlated with neutrophils ( P<0.05) . Conclusion:High expression of COL1A1 and COL1A2 genes in MPM tissues is valuable for diagnosis, disease prediction and prognostic assessment of MPM, and both may jointly contribute to the development of MPM.

Objective:To combine micro-course and flipped classroom, integrate the application of online WeChat group and teaching video, build a new teaching framework, and seek the application of flipped classroom based on "micro-course" in clinical skills training of general anesthesia and tracheal intubation for medical students.Methods:A total of 82 clinical medicine intern students of Batch 2015 and 2016 from Nnajing Drum Tower Hospital were selected as the research subjects to complete the internship (for two weeks). The teaching reform group (44 people) adopted the flipped classroom based on "micro-course"; the traditional group (38 people) adopted traditional teaching. Organized by the undergraduate teaching and research department, the number of tracheal intubation cases and the number of excellent scores were recorded during the two-week internship in anesthesia. After the rotation, a questionnaire survey was conducted to evaluate the mastery of endotracheal intubation operation and satisfaction with the teaching and training arranged by the department. SPSS 23.0 was used to conduct t test and non-parametric test. Results:The number of outstanding cases of tracheal intubation in the teaching reform group was higher than that in the traditional group, and the number of outstanding cases of tracheal intubation in girls was higher than that in boys, and the difference was statistically significant ( P<0.05). The self-assessed scores of the students' mastery of tracheal intubation and the satisfaction with clinical practice training in the teaching reform group were higher than those in the traditional group, and the difference was statistically significant ( P<0.05). Conclusion:Compared with traditional teaching, the flipped classroom based on "micro-course" has more advantages in the clinical skills training of medical tracheal intubation.

Objective:To investigate the expression levels and clinical significance of collagen typeⅠ α1 chain (COL1A1) and collagen type Ⅰ α2 chain (COL1A2) in malignant pleural mesothelioma (MPM) tissues.Methods:In January 2020, MPM tissues and adjacent normal pleural tissues were collected from 26 MPM patients, and the expression levels of COL1A1 and COL1A2 genes in the tissues were determined by quantitative reverse transcription PCR, and the efficacy of both levels in diagnosing MPM was assessed using receiver operating characteristic (ROC) curves. The relationship between COL1A1 and COL1A2 gene expression and clinicopathological features was analyzed by the Cancer Genome Atlas (TCGA) database, and the relationship between the expression levels of both and overall survival (OS) and disease-free progression survival (DFS) of MPM patients was dynamically analyzed by gene expression profiling, and the factors affecting the prognosis of MPM patients were explored by Cox proportional risk regression model. The TIMER 2.0 platform was used to explore the relationship between COL1A1 and COL1A2 gene expression in MPM and tumor immune infiltrative cells.Results:Compared with normal pleural tissues, the expression of COL1A1 and COL1A2 genes was significantly increased in MPM tissues ( P<0.01) , and their expression was positively correlated ( P<0.001) . The ROC curves showed that the area under the curve for COL1A1 and COL1A2 expression levels diagnostic of MPM was 0.900 and 0.897, respectively. The expression of COL1A1 gene was correlated with tumor type in MPM patients ( P<0.05) , and COL1A2 gene expression was correlated with T stage in MPM patients ( P<0.05) . Both COL1A1 and COL1A2 gene expression were associated with OS in MPM patients (Logrank P<0.05) , but there was no significant correlation with DFS (Logrank P>0.05) . Cox multivariate analysis showed that patients with high COL1A1 and COL1A2 gene expression and biphasic mixed MPM had a higher risk of death ( P<0.05) . TIMER 2.0 platform analysis showed that COL1A1 and COL1A2 gene expression in MPM patients was positively correlated with macrophages, COL1A2 gene expression in MPM was negatively correlated with neutrophils ( P<0.05) . Conclusion:High expression of COL1A1 and COL1A2 genes in MPM tissues is valuable for diagnosis, disease prediction and prognostic assessment of MPM, and both may jointly contribute to the development of MPM.

Objective:To evaluate the effect of α-ketoglutarate (AKG) on postoperative delirium (POD) in aged mice.Methods:Eighty male C57BL/6N mice, aged 18 months, weighing 30-35 g, were divided into 4 groups ( n=20 each) using a random number table method: control+ solvent group (group C), control+ AKG group (group C+ AKG), surgery+ solvent group (group S) and surgery+ AKG group (group S+ AKG). Dimethyl 2-oxoglutarate 0.6 mg/kg was injected intraperitoneally for 3 consecutive days before surgery in C+ AKG and S+ AKG groups, while the equal volume of normal saline was given in C and S groups.Exploratory laparotomy was performed under anesthesia with isoflurane to establish POD model.The behaviors of mice in each group were tested at 24 h before surgery and 6, 9 and 24 h after surgery using buried food test (the latency to eat food), open field test (total distance, latency to the center, time and freezing time spent in the center) and Y maze test (duration in the novel arm and the number of entries into the novel arm), respectively.Then the animals were sacrificed at 6 h after operation, hippocampal tissues were removed for determination of the expression of microglia-specific marker ionized calcium binding adaptor molecule-1 (Iba-1), the number of Iba-1 positive cells (using immunofluorescence staining), and the expression of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in hippocamapus (by Western blot). Results:Compared with group C, the latency to eat food at eath time point was significantly prolonged, latency to the center at 6 and 9 h after surgery was prolonged, time spent in the center at 6 and 9 h after surgery was shortened, freezing time at 6, 9 and 24 h after surgery was shortened, the number of entries into the novel arm at 6 and 9 h after surgery was decreased, duration in the novel arm at 6 h after surgery was shortened, the expression of Iba-1 was up-regulated, the number of Iba-1 positive cells was increased, and the expression of IL-1β and TNF-α in hippocampus was up-regulated in group S ( P<0.05), and no significant change was found in the behaviors indexes in group C+ AKG ( P>0.05). Compared with group S, the latency to eat food at each time point was significantly shortened, latency to the center at 9 h after surgery was shortened, time spent in the center at 6 and 9 h after surgery was prolonged, freezing time at 9 and 24 h after surgery was prolonged, the number of entries in the novel arm at 9 h after surgery was increased, the expression of Iba-1was down-regulated, the number of Iba-1 positive cells was decreased, and the expression of IL-1β and TNF-α in hippocampus was down-regulated in group S+ AKG ( P<0.05). Conclusion:AKG can alleviate POD, and the mechanism may be related to inhibiting the activation of microglia and and thus reducing inflammatory responses in aged mice.

BACKGROUND: Lung cancer is one of the malignant tumors. Gene mutations associated with cellular immune function and regulating the activation and proliferation of immune cells. Several publications have explored the relationship between cytotoxic T lymphocyte antigen-4 (CTLA-4) +49 adenine (A)/guanine (G) polymorphism and susceptibility of lung cancer, but the results remain controversial. Thus, we performed this meta-analysis to derive a more comprehensive estimation of the relationship. METHODS: All articles addressed lung cancer and polymorphisms of CTLA-4 were searched from the PubMed, EMBASE databases published up to June 29, 2019. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Publication bias of relevant studies was examined via Begg's test and funnel plots. RESULTS: The meta-analysis included 8 case-control studies covering 4,430 lung cancer patients and 5,198 healthy controls from September 2008 to April 2020. The overall eligible data indicated that CTLA-4 +49A/G polymorphisms did not correlate with the elevated lung cancer risk in all genetic comparison models (dominant model: OR=1.037, 95%CI: 0.925-1.161; recessive model: OR=0.968, 95%CI: 0.888-1.055; allele model: OR=0.992, 95%CI: 0.933-1.054; homozygous model: OR=0.980, 95%CI: 0.857-1.121; heterozygous model: OR=1.023, 95%CI: 0.906-1.154). In further stratified analyses, CTLA-4 +49A/G polymorphism was found to be significantly associated with susceptibility to NSCLC in these models (dominant model: OR=1.404, 95%CI: 1.074-1.836; allele model: OR=1.273, 95%CI: 1.034-1.565; homozygous model: OR=1.553, 95%CI: 1.044-2.310; heterozygous model: OR=1.308, 95%CI: 1.062-1.611). CONCLUSIONS CTLA-4 +49A/G polymorphism were not associated with the risk of lung cancer but might be a risk factor only in NSCLC.

Objective:To investigate the current situation of clinical nurses' anxiety about obtaining information and analyze the influencing factors of information anxiety degree.Methods:The convenient sampling method was used to conduct a cross-sectional survey, and 339 clinical nurses from 4 general hospitals in Nanjing from April to June 2020 were selected as the research objects. The general information questionnaires and Information Anxiety Scale were used for the investigation. In this study, a total of 339 questionnaires were issued and 324 valid questionnaires were returned, with an effective recovery rate of 95.58%.Results:The total score of Information Anxiety Scale of 324 clinical nurses was (100.96±19.83) and the average score of items was (2.69±0.25) . The average scores of each dimension item from high to low were information demand, information utilization ability, retrieval system quality, information retrieval ability, cognitive type and knowledge structure. The results of multiple linear regression analysis showed that age, professional title, education level and hospital grade were the main factors affecting the degree of information anxiety of clinical nurses ( P<0.05) . Conclusions:Age, professional title, education level and hospital grade are the main influencing factors of information anxiety degree of clinical nurses. Nursing managers should cultivate the awareness of information acquisition of clinical nurses and enhance their ability to acquire information independently, so as to reduce their anxiety about acquiring information.