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 analyze the risk of re-displacement after external fixation treatment for distal radius fractures in older adult patients and establish a nomogram model.Methods:A retrospective analysis was conducted on the clinical data of 96 older adult patients with distal radius fractures who were treated with external fixation at Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from January to December 2022. Based on whether re-displacement of the fracture occurred, the patients were divided into an observation group (re-displacement occurred, n = 15) and a control group (no re-displacement occurred, n = 81). Univariate and logistic regression analyses were used to identify risk factors, and a nomogram model was established. Results:There were statistically significant differences between the two groups in terms of age ( t = 2.13, P = 0.036), sex ( χ2 = 4.17, P = 0.041), presence of comminution ( χ2 = 14.18, P < 0.001), fracture type ( χ2 = 49.59, P < 0.001), body mass index ( t = 3.01, P = 0.003), number of adjustments to external fixation ( χ2 = 4.17, P = 0.041), presence of bone resorption or necrosis ( χ2 = 13.96, P < 0.001), appropriateness of external fixation management ( χ2 = 21.43, P < 0.001), and reasonableness of functional exercise ( χ2 =23.67, P < 0.001). Independent risk factors for the occurrence of re-displacement after external fixation treatment for distal radius fractures in older adult patients included age ( OR = 3.07, P = 0.002), sex ( OR = 3.11, P = 0.007), presence of comminution ( OR = 2.56, P = 0.039), presence of bone resorption or necrosis ( OR = 5.70, P < 0.001), and reasonableness of functional exercise ( OR = 3.04, P < 0.001). The discrimination analysis of the nomogram model showed an area under the curve of 0.855, with a 95% CI of 0.853 to 0.927, and a critical value of 31.25% ( P < 0.001). The GiViTI calibration curve showed that the 80%-90% confidence intervals did not cross the 45° bisector in the graph ( P > 0.05). The Hosmer-Lemeshow goodness-of-fit test showed no statistically significant difference ( χ2 = 5.29, P = 0.582). The decision curve analysis indicated that when the risk of re-displacement exceeded 33.64% in older adult patients undergoing external fixation for distal radius fractures, the net benefit of intervening in these patients was maximized. Conclusions:Age, sex, presence of comminution, presence of bone resorption or necrosis, and the reasonableness of functional exercise are independent risk factors for re-displacement after external fixation treatment of distal radius fractures in older adult patients. The higher the score on the nomogram model, the greater the risk of fracture re-displacement in the patient.

Objective:To analyze the risk of re-displacement after external fixation treatment for distal radius fractures in older adult patients and establish a nomogram model.Methods:A retrospective analysis was conducted on the clinical data of 96 older adult patients with distal radius fractures who were treated with external fixation at Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from January to December 2022. Based on whether re-displacement of the fracture occurred, the patients were divided into an observation group (re-displacement occurred, n = 15) and a control group (no re-displacement occurred, n = 81). Univariate and logistic regression analyses were used to identify risk factors, and a nomogram model was established. Results:There were statistically significant differences between the two groups in terms of age ( t = 2.13, P = 0.036), sex ( χ2 = 4.17, P = 0.041), presence of comminution ( χ2 = 14.18, P < 0.001), fracture type ( χ2 = 49.59, P < 0.001), body mass index ( t = 3.01, P = 0.003), number of adjustments to external fixation ( χ2 = 4.17, P = 0.041), presence of bone resorption or necrosis ( χ2 = 13.96, P < 0.001), appropriateness of external fixation management ( χ2 = 21.43, P < 0.001), and reasonableness of functional exercise ( χ2 =23.67, P < 0.001). Independent risk factors for the occurrence of re-displacement after external fixation treatment for distal radius fractures in older adult patients included age ( OR = 3.07, P = 0.002), sex ( OR = 3.11, P = 0.007), presence of comminution ( OR = 2.56, P = 0.039), presence of bone resorption or necrosis ( OR = 5.70, P < 0.001), and reasonableness of functional exercise ( OR = 3.04, P < 0.001). The discrimination analysis of the nomogram model showed an area under the curve of 0.855, with a 95% CI of 0.853 to 0.927, and a critical value of 31.25% ( P < 0.001). The GiViTI calibration curve showed that the 80%-90% confidence intervals did not cross the 45° bisector in the graph ( P > 0.05). The Hosmer-Lemeshow goodness-of-fit test showed no statistically significant difference ( χ2 = 5.29, P = 0.582). The decision curve analysis indicated that when the risk of re-displacement exceeded 33.64% in older adult patients undergoing external fixation for distal radius fractures, the net benefit of intervening in these patients was maximized. Conclusions:Age, sex, presence of comminution, presence of bone resorption or necrosis, and the reasonableness of functional exercise are independent risk factors for re-displacement after external fixation treatment of distal radius fractures in older adult patients. The higher the score on the nomogram model, the greater the risk of fracture re-displacement in the patient.

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.

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.

[Abstract] Objective: To investigate the pathogenesis of prostate cancer by analyzing the associated hub gene modules of prostate cancer and identifying key transcription factors and genes that affect these modules. Methods: WGCNA (weighted gene co-expressed network analysis) was used to identify hub gene modules associated with important clinicopathological features of prostate cancer, such as pathological staging, Gleason grading etc. The OPOSSUM online tool was used to analyze the transcription factors enriching and regulating those genes. Pathway enrichment analysis and protein-protein interaction network analysis were used to identify key genes in prostate cancer. Finally, the effects of these genes on clinical features and disease-free survival (DFS) of prostate cancer patients were analyzed. Results: Three hub modules were identified, and they were highly associated with pathologic T stage, pathologic N stage and Gleason grading of prostate cancer, respectively. Further screening revealed 13 key dysregulated transcription factors that participated in the regulation of these three hub modules. The differentially expressed genes regulated by the 13 key transcription factors were significantly enriched in Calcium signaling pathway, cGMP-PKG signaling pathway and cAMP signaling pathway. 14 key genes (PRKG1, PRKG2, CYSLTR2, GRPR, CHRM3, ADCY5, ADRA1D, EDNRA, EDNRB, CYSLTR2, AGTR1, GRPR, GRIA1 and OXT) were at important nodes in the gene network. Among them, the high expression of ADRA1A, PRKG2, CHRM3, ADRA1D and EDN3 significantly extended the DFS of patients with prostate cancer (all P<0.01). Conclusion: ADRA1A, PRKG2, CHRM3, ADRA1D and EDN3 are regulated by key dysregulated transcription factors and highly associated with clinical features of prostate cancer. Their high expressions will significantly prolong the DFS of prostate cancer patients, which may shed light to the discovery of mechanism in prostate adenocarcinoma.

OBJECTIVETo optimize the condition of callus of Cinnamonum camphora induced.

METHODGC and plant tissue culture method were applied in the study.

RESULTThe effect of callus induced and the growth of callus were different in MS medium with different proportion of hormone. The ration of callus induced was the highest and the growth of callus was the most prosperous in the MS medium with 4 mg x L(-1) 2,4-D and 0.2 mg x L(-1) 6-BA. It is found that callus induced by young leaf contained borneol, but callus induced by young stem not.

CONCLUSIONThe optimization of callus of C. camphora induced is using the MS medium with 4 mg x L(-1) 2,4-D + 0.2 mg x L(-1) 6-BA. Callus induced by young leaf can generate borneol.

Bornanes ; metabolism ; Cinnamomum camphora ; growth & development ; metabolism ; Culture Media ; Tissue Culture Techniques