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 effectiveness and safety of autologous fat granule transplantation for facial rejuvenation.Methods:Databases including PubMed, Cochrane Library, Google Scholar, Web of Science, China Biology Medicine Database, Wanfang Database, and CNKI were searched. The search time range was from 2013 to 2023. Search key words included autologous fat transplantation, facial rejuvenation, efficacy, effectiveness, safety, complications, etc. Meta-analysis was used. Literature search was conducted by using tool method and forward search method. OR (95% CI) was used as the statistical measure for efficacy analysis. Heterogeneity of literature was tested by I2 test. Publication bias was tested by Begg′ s test. Results:A total of 23 literatures were included, covering 2 852 beauty seekers. There was no significant publication bias. The satisfactory rate of beauty seekers after autologous granular fat transplantation was relatively high ( OR=0.95, 95% CI: 0.91-0.97). The success rate of one-time injection was relatively high ( OR=0.79, 95% CI: 0.73-0.84). The incidence of postoperative complications was relatively low ( OR=0.02, 95% CI: 0.01-0.04). Conclusion:Autologous fat granule transplantation surgery has good effectiveness and safety for facial rejuvenation.

Objective:To investigate the efficacy of neostigmine combined with raw rhubarb enema on severe acute pancreatitis (SAP) patients with intra-abdominal hypertension (IAH).Methods:The clinical data of 89 SAP patients, who were admitted and underwent continuous renal replacement treatment (CRRT) in intensive care unit (ICU) department of the First Affiliated Hospital of Hebei North University from January 2018 to June 2022, were retrospectively analyzed. Patients were divided into control group ( n=44) and experimental group ( n=45) according to the treatment mode. Raw rhubarb enema plus sodium sulfate topical application were administrated twice a day for 7 days in control group; besides the treatment above, intramuscular injection of neostigmine 0.5 mg twice a day for 7 days was given in experimental group. Intra-abdominal pressure was monitored, acute physiology and chronic health evaluation (APACHE)Ⅱ, kidney disease: improving global outcome stage (KDIGO), lung injury score (LIS) were recorded, and serum leukocyte, CRP, procalcitonin (PCT), IL-6, IL-8 and tumor necrosis factor (TNF)-ɑ level were examined before and after treatment in both groups. The primary endpoint was the amount change of intra-abdominal pressure within 24 hours, and secondary endpoints included increased fecal volume within 7 days after treatment, new abdominal compartment syndrome (ACS), new organ dysfunction, vascular complications, length of ICU stay, total length of stay, survival rate and treatment intervention and occurrence of complications within 6 months after the end of treatment. Results:Intra-abdominal pressure began to decrease at 9 hours after treatment both in control group and experimental group. Compared with that before treatment, the intra-abdominal pressure of the two groups decreased significantly after 7 days of treatment, and the decrease rate of the experimental group within 7 days was obviously higher than that of the control group, with statistical significance (all P values <0.05). Compared with those before treatment, APACHEⅡ, KDIGO and LIS in both groups were significantly decreased, but the decreases in experimental group were more remarkable than those in control group (all P values <0.05). After treatment, the serum WBC count and the levels of inflammatory factors CRP, PCT, IL-6, IL-8, TNF-ɑ in experimental group were obviously lower than those in control group with statistical significance (all P values <0.05). Compared with control group, the change of intra-abdominal pressure in experimental group was significantly increased after 24-hour treatment, and the fecal volume was also obviously increased on day 1, 2, 3, 5 and 7 after treatment (all P values <0.05). However, there were no significantly statistical differences on the severity of intra-abdominal pressure, new occurrence of ACS and organ failure, vascular complication, ICU hospitalization and total length of stay and survival rate between two groups. After 6-month follow-up, the recurrence of pancreatitis and its treatment intervention between two groups were not statistically significant. Conclusions:The adjuvant treatment of neostigmine could reduce intra-abdominal pressure, increase defecation volume in SAP patients and alleviate SAP condition, which might be related to reducing the release of inflammatory cytokines.

Objective To establish the model of goat intervertebral disc degeneration （IDD） induced by controllable axial compressive stress and evaluate its imaging and pathological characteristics. Methods Twenty goats were randomly divided into 4 groups (control group, 4-week pressure group, 8-week pressure group, 12-week pressure group, n=5, 40 N pressure). Disc height index (DHI) was used to evaluate the change of intervertebral disc height by X-ray, Pfirrmann classification method was used to observe the degree of intervertebral disc degeneration by magnetic resonance imaging (MRI), and histopathological observation and evaluation for intervertebral disc were conducted by HE staining and immunohistochemistry. Results DHI in control group showed no significant changes with the extension of pressure time, while DHI in the experimental group gradually decreased. There was no significant change in Pfirrmann classification in control group. In experimental group, with the extension of time, the higher the degeneration aggravated with the Pfirrmann classification increasing. In experimental group, HE staining showed that the disc nucleus pulposus decreased in volume and nucleus pulposus cells, which were gradually replaced by fibrous tissues. Immunohistochemical staining showed that type I collagen in the nucleus pulposus gradually increased, type Ⅱ collagen gradually decreased, and intervertebral disc degeneration occurred. Conclusions A certain axial compressive stress can lead to degeneration of goat lumbar intervertebral disc, and the degree of degeneration is gradually increased with the extension of time.

OBJECTIVE: To explore the effect of clinical pathway of emergency respiratory and cardiac arrest on management of patients with sudden respiratory and cardiac arrest. METHODS: The clinical data of patients with sudden respiratory and cardiac arrest admitted to Huashan North Hospital Affiliated to Fudan University from 1 year before to 1 year (started in July 2017) after the implementation of clinical pathway of emergency respiratory and cardiac arrest were retrospectively analyzed. The patients who managed by clinical pathway of emergency respiratory and cardiac arrest (from July 2017 to June 2018) were served as observational group, and those manually managed by 2015 American Heart Association cardiopulmonary resuscitation and cardiovascular emergency guide update and the procession in the management of emergency key diseases (from July 2016 to June 2017) were set as control group. The gender, age, underlying disease, the initiation time of cardiopulmonary resuscitation (CPR), the first time of defibrillation, the completion time of endotracheal intubation, the time of venous access, the usage time of the first dose of adrenaline, the usage time of vasoactive drugs, the completion rate of high quality CPR, the success rate of return of spontaneous circulation (ROSC) and the table procedure of clinical pathway were compared between the two groups. RESULTS: There was no statistically significant difference in gender, age or underlying disease between the two groups. Compared with the control group, the clinical pathway could effectively guide the decision-making of the emergency medical staffs, significantly reduce the variation in the procession of the resuscitation, the first time of defibrillation, the completion time of the deep vein catheterization, the usage time of norepinephrine and the completion time of the blood specimen delivery were significantly shortened [the first time of defibrillation (minutes): 1.28±0.86 vs. 2.93±1.61, the completion time of deep vein catheter (minutes): 15.13±2.73 vs. 17.25±3.02, the usage time of norepinephrine (minutes): 15.43±2.80 vs. 17.88±1.67, the completion time of blood specimen delivery (minutes): 7.81±1.42 vs. 9.00±1.03, all P < 0.05]. There was no statistically significant difference in the initiation time of CPR, the completion time of tracheal intubation, the time of peripheral venous access, the usage time of the first dose of adrenaline or sodium bicarbonate, or the success rate of ROSC between the two groups. However, the usage time of the first dose of adrenaline and sodium bicarbonate was shortened in the observation group [the usage time of the first dose of adrenaline (minutes): 3.81±1.22 vs. 4.00±1.32, the usage time of the first does of sodium bicarbonate (minutes): 8.94±3.49 vs. 11.19±3.54, both P > 0.05], and the success rate of ROSC was relatively increased as compared with those in the control group [15.04% (17/113) vs. 12.50% (12/96), P > 0.05]. CONCLUSIONS The clinical pathway of emergency respiratory and cardiac arrest could effectively guide the clinical decision-making of the emergency medical staffs, significantly reduce the variation in the procession of the resuscitation, improve the quality of the resuscitation, and ensure medical safety of emergency department.
Cardiopulmonary Resuscitation ; Case-Control Studies ; Critical Pathways ; Electric Countershock ; Emergency Service, Hospital ; Female ; Health Services Research ; Heart Arrest/therapy* ; Humans ; Male ; Retrospective Studies

Objective To observe the accuracy of the five-level adult emergency triage system (FLAETS) in determining the severity of critically ill patients,and to analyze the factors that influenced the accuracy of the triage.Methods The triage information of patients admitted to Huashan North Hospital Affiliated to Fudan University between 1 year before and 1 year (started in July 2014) after the implementation of the FLAETS were retrospective analyzed.The patients who triaged by FLAETS (from September 2014 to August 2015) were served as observational group,and those manual triaged by modified early warning score (MEWS,from July 2013 to June 2014) were set as control group.The patients with triage of Ⅰ,Ⅱ,and Ⅲ levels were enrolled (fatal,critical,urgent),and the triage results of emergency physicians-in-chief on duty were set as gold standard.The gender,age,triage level,the proportion of over-triage,the proportion of under-triage,and mortality were compared between two groups.The reasons for the overtriage and under-triage were analyzed.The accuracy of FLAETS in determining severity of critically ill patients was calculated.Results 18449 patients were enrolled in observational group,and 720,1641 and 16088 patients were triaged as level Ⅰ,level ⅡⅡ,level Ⅲ respectively;17 378 patients were triaged as critically ill patients according to gold standard,and level Ⅰ,level Ⅱ,level Ⅲ were 637,1476 and 15 265 patients respectively.6 352 patients were enrolled in control group,and level Ⅰ,level Ⅱ,level Ⅲ were 204,771 and 5 377 patients respectively;6002 patients were triaged as critically ill patients according to gold standard,and level Ⅰ,level Ⅱ,level Ⅲ were 308,836 and 4 858 patients respectively.There were no statistically significant differences in gender and age between two groups (both P ＞ 0.05).Compared with the control group,the proportion of over-triage of level Ⅲ was significantly lowered [8.3％ (1 329/16088) vs.12.5％ (674/5 377),P ＜ 0.01],the proportion of under-triage of level Ⅱ and level Ⅲ was significantly lowered [level Ⅱ:0.6％ (9/1 641) vs.7.0％ (54/771),level Ⅲ:0.4％ (63/16088) vs.4.7％ (254/5 377),both P ＜ 0.01].The success rate of resuscitation in observation group was significantly higher than that of control group [80.70％ (619/767) vs.75.23％ (410/545),P =0.020],and the mortality was significantly lowered [1.11％ (193/17 378) vs.2.35％ (141/6002),P =0.037].Over-triages were mainly found in patients with chronic obstructive pulmonary disease (COPD),hypertension and the main complaint of chest tightness,shortness of breath,and under-triages were mainly found in patients with the multiple organ dysfunction in the elder,atypical heart disease and pneumothorax.The accuracy rates of level Ⅰ,level Ⅱ and level Ⅲ in observation group (99.37％,97.42％ and 89.58％) were significantly higher than those of the control group (97.51％,92.54％,and 80.16％,all P ＜ 0.01).Conclusion The FLAETS in determining severity of critically ill patients were objective and reliable,which enable the nurse to better handle the relationship of the emergency and the ordinary,the severe and the mild,the priority and the non-priority,which made the patients received timely and effective treatment.