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 relevant factors affecting the accuracy of scanning glucose monitoring (FGM) technology in critically ill patients.Methods:A total of 53 patients who were admitted to the Intensive Care Unit (ICU) of the Second Affiliated Hospital of Soochow University and used FGM glucose monitoring from September 2022 to December 2023 were selected by means of a convenience sampling method. The paired data of arterial blood glucose and FGM glucose were analysed. The accuracy of FGM blood glucose measurement in critically ill patients was evaluated using Bland-Altman analysis. The blood glucose data were divided into two groups: the FGM monitoring accuracy group and the FGM monitoring non-accuracy group.. The t-test and χ2 test were used for the comparison of one-way analysis of arterial versus FGM accuracy among critically ill patients with different demographic characteristics. Logistic regression analysis was used to analyze the factors influencing the accuracy of FGM. Results:The results of Bland-Altman analysis of the 53 patients indicated that the mean bias value of FGM blood glucose was elevated at 1.215 mmol/L in comparison with arterial-blood gas analysis blood glucose values. An incidence of exceeding the upper and lower limits of the range was observed, amounting to 6.349%. The discrepancy between the studies was found to be statistically significant (95% CI:1.0394~1.3908, P<0.001). The effects of the changes in height ( OR=0.877, 95% CI:0.780~0.987, P=0.029), changes in leukocyte counts( OR=0.917, 95% CI:0.868~0.969, P=0.002), changes in C-reactive protein( OR=1.009, 95% CI:1.002~1.017, P=0.016), changes in albumin counts( OR=0.986, 95% CI:0.974~0.999, P=0.031), and whether or not sepsis ( OR=3.937, 95% CI:1.192~13.008, P=0.025) on the accuracy of FGM had a statistically significant. Conclusion:The mean bias value of the accuracy of FGM was relatively higher compared with that of arterial blood gas analysis blood glucose values, and the influencing factors involved height, white blood cells, C-reactive protein, albumin, and whether or not sepsis was present. With the development of science and technology, applying the FGM system to critically ill patients has an absolute advantage in determining the overall glycemic trend, and the application value of FGM technology deserves further study.

Objective:To evaluate the utility of ultrasonographic monitoring of the rectus femoris muscle—specifically, the rates of change in thickness and cross-sectional area (CSA)—in assessing nutritional status and long-term functional outcomes in patients with sepsis.Methods:In this prospective observational study, sepsis patients admitted to the ICU of the Second Affiliated Hospital of Soochow University between October 2023 and October 2024 were classified by nutritional status at discharge using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Differences in serial ultrasound-measured rectus femoris thickness and CSA on days 1, 3, 5, and 7 were compared between malnourished and non-malnourished groups. The predictive value of these ultrasound parameters for malnutrition was analyzed. Functional prognosis was assessed using the Sarcopenia Assessment Scale, Short Physical Performance Battery, and Manual Muscle Testing, with correlations to muscle changes examined.Results:Of the 71 enrolled patients (median age 73.00 [ IQR: 61.00–80.00]; 47.89% female, 52.11% male), those with malnutrition showed significantly greater variation rates in rectus femoris thickness and CSA on days 3, 5, and 7 compared to the non-malnourished group ( P < 0.05). ROC analysis revealed that the day-7 CSA variation rate had the highest predictive value for malnutrition (AUC = 0.817, 95% CI: 0.713-0.930). These muscle variation rates also correlated strongly with conventional nutritional markers such as BMI, albumin, and urea. Similarly, patients with impaired functional outcomes exhibited higher variation rates in muscle parameters on days 3, 5, and 7 ( P < 0.05), with the day-7 CSA variation rate being most predictive of functional prognosis (AUC = 0.749, 95% CI: 0.632-0.867). Conclusions:Ultrasonographic assessment of rectus femoris thickness and CSA variation rates provides a valuable tool for evaluating nutritional status and predicting functional prognosis in sepsis patients, outperforming traditional biomarkers. This method shows promise for guiding individualized nutrition support and rehabilitation strategies to improve long-term outcomes.

Objective To compare the image quality of carotid contrast-enhanced magnetic resonance angiography(ceMRA)under different flow rates using high relaxation rate contrast agent named Gadobutrol,and to find the best flow rate for carotid ceMRA.Methods Total of 117 patients,who were scheduled to perform carotid ceMRA examination using Gadobutrol with a dosage of 0.1 mL/kg body weight on a 1.5T MR platform,were enrolled in the study.They were divided into four groups according to four kinds of flow rates,which were 1.0 mL/s(n=29),1.5 mL/s(n=30),2.0 mL/s(n=30)and 3.0 mL/s(n=28).The signal-to-noise ratio(SNR)of bilateral carotid initiation and bilateral carotid bifurcation were calculated.The SNR of carotid initiation or carotid bifurca-tion between different flow rates were compared.And the scores of image quality among different flow rates were also compared.Results For bilateral carotid bifurcations and carotid initiations,the SNR under 1.5 mL/s were highest,which were significantly higher than those under 1.0 mL/s,while there were no significant differences between each two other flow rates.For the bilateral carotid bifurca-tions,the SNR under 1.0 mL/s were lower than those under other flow rates,and were significantly lower than those under 1.5 mL/s and 3.0 mL/s.The score of the image quality at 1.0 mL/s was significantly lower than that under other flow rates.The score of the image quality at 1.5 mL/s was the highest,but no significant difference was found compared to that at 2.0 mL/s or 3.0 mL/s.Conclusion The rate of 1.5 mL/s is recommended as the best flow rate for carotid ceMRA with Gadobutrol based on 1.5T MR.

Objective:To compare the clinical efficacy of fluorescent laparoscopy versus conventional laparoscopy for living-donor hepatectomy and explore the application value of fluorescent cholangiography in pediatric living donor liver transplantation (LT) using left lateral lobe.Methods:From October 2016 to August 2023, retrospective analysis was conducted for the relevant clinical data from 302 recipients of laparoscopic left lateral lobe donor hepatectomy. There were 90 cases in conventional laparoscopy group and 212 cases in fluorescent laparoscopy group. After propensity score matching (PSM), 88 patients were enrolled into each group. The perioperative data such as operative duration, donor liver thermal ischemic time, number of graft bile duct openings, liver function parameters and complication rates at Day 1/3 postoperation of donors and recipients were compared between two groups. SPSS 27.0 statistical software was utilized for analysis. Independent sample t, Mann-Whitney U and chisquare tests were utilized for examining the inter-group differences. Results:In fluorescent laparoscopy group, the proportion of grafts with a single open left hepatic duct was 84.1 %(74/88) versus 70.5% (62/88) in conventional laparoscopy group with statistically significant difference ( P=0.031). No statistically significant inter-group differences existed in postoperative liver function recovery or short-term postoperative complications ( P>0.05 ). No statistically significant inter-group differences existed in short-term postoperative liver function recovery or hospitalization length ( P> 0.05). In terms of biliary complications, fluorescent laparoscopy group had no biliary complications while the incidence of biliary complications was 3.4% (3/88) in conventional laparoscopy group. However, inter-group difference was statistically insignificant ( P>0.05 ) . Conclusions:Living-donor LT using left lateral lobe under fluorescent laparoscopy may enhance the surgical safety for both donors and recipients.

In November 2023, the seventh National Nucleic Acid Vaccine Conference was held to deeply discuss the immune mechanism, safety risks, advantages, and disadvantages of nucleic acid vaccines, and review the safety and effectiveness of COVID-19 vaccines developed by nucleic acid vaccine technology. Some prospectives were formed in the meeting that in the post-pandemic era, nucleic acid vaccine technology will play a role in the following areas: dealing with pathogens that are difficult to be prevented by traditional vaccines, promoting the upgrading of traditional live attenuated vaccines, contributing to the development of multivalent and combined vaccines, and rapid response to emerging and re-emerging infectious diseases. These views point out the direction for the future development of nucleic acid vaccine technology.

Objectives:To identify the risk factors associated with delirium in intensive care unit (ICU) hospitalization of sepsis patients and construct a clinical prediction model to to provide a reference for the prevention and control of delirium in sepsis patients.Methods:Data were collected of sepsis patients admitted in the Intensive Care Unit in the Second Affiliated Hospital of Soochow University from September 2020 to August 2022.The patients were divided into delirium group and non-delirium group according to whether delirium occurred or not. Comparing of the differences in general and clinical data between the two groups, the independent risk factors for delirium were screened by backward stepwise regression method, and the delirium risk prediction model was constructed and evaluated. An independent risk factor analysis for delirium was conducted using a backward stepwise regression approach to identify significant predictors. A delirium risk prediction model was constructed based on the identified risk factors, followed by a comprehensive evaluation of the model's performance.Results:A total of 381 sepsis patients were included in the study, 114 patients (29.9%) developed delirium during the ICU hospitalization. Univariate analysis revealed statistically significant differences ( P< 0.05) between the delirium and non-delirium groups for several factors including age ≥ 65 years, blood transfusion, use of midazolam, use of adrenaline, APACHEⅡ score>15, SOFA score>4, metabolic acidosis, urea>7.1 mmol/L, coagulation disorders, lactate levels, and platelet count. Multivariate analysis identified age ≥ 65 years, use of midazolam, APACHEⅡ score>15, metabolic acidosis, urea>7.1 mmol/L, and coagulation disorders as independent risk factors for delirium in sepsis patients during ICU hospitalization.The predictive model was evaluated with an area under the ROC curve of 0.813, a non-significant Hosmer-Lemeshow goodness-of-fit test ( P=0.957>0.05), and a Brier score of 0.149 (<0.25), indicating good predictive performance and calibration. Clinical decision and impact curves demonstrated the model's favorable clinical applicability. Conclusions:The occurrence of delirium in ICU sepsis patients closely associate with six factors: age ≥ 65 years, use of midazolam, APACHEⅡ score>15, metabolic acidosis, urea>7.1 mmol/L, and coagulation disorders. This sepsis delirium prediction model has good clinical predictive ability and clinical applicability.

Purpose To evaluate the carotid artery elasticity and the influencing factors in the offspring of early-onset type 2 diabetes mellitus by RF-data based quantitative analysis on vessel stiffness.Materials and Methods We continuously encrolled 63 offspring of type 2 diabetes mellitus,depending on the parental diagnostic age of diabetes they were divided into two groups:32 cases of early-onset offspring group,31 cases of late-onset offspring group.32 healthy volunteers who were matched for age,gender and body mass index,were selected as controls.Real-time intima-media thickness and RF-data based quantitative analysis on vessel stiffness were employed to evaluate common carotid intima-media thickness,displacement,diameter,hardness coefficient and pulse wave velocity.The differences among the groups were compared.Results The intima-media thickness,pulse wave velocity and hardness coefficient in early-onset offspring group were higher than late-onset offspring group(t=0.054-1.228,P＜0.05),and displacement was lower than late-onset offspring group(t=0.048,0.109,both P＜0.05).Conclusion Carotid artery stiffness in the offspring of diabetes mellitus patients is significantly higher than the control group.And the carotid elasticity of early-onset offspring group decreased more obviously than late-onset group.

Objective To investigate the efficacy of transcranial direct current stimulation(tDCS)on sleep disorder in patients with Parkinson's disease(PD).Methods From July 2021 to July 2023,patients with PD and sleep disorders in the Department of Neurosurgery of the Second People's Hospital of Guangdong Province were selected.The enrolled patients were divided into sham stimulation group(n=28)and true stimulation group(tDCS)(n=29)according to the inclusion and exclusion criteria.MDS-UPDRS,PDSS and other rating scales were used to evaluate the patients.Before and after tDCS treatment,MS-11 was used for intelligent sleep monitor-ing.The baseline and improvement of sleep disorders in the two groups before and after treatment were analyzed.Results Before tDCS treatment,there was no significant difference in general conditions and scale scores between the two groups(P＞0.05).There was no significant difference in polysomnographic monitoring results between the two groups before treatment(P＞0.05).Compared with pre-treatment,there was no significant difference in sleep monitoring results in the sham stimulation group(P＞0.05),while the sleep duration and sleep efficiency signifi-cantly increased,the nighttime awakening duration,nighttime awakening frequency,MDS-UPDRS-Ⅲ score,and LEDD dose significantly decreased in the true stimulation group,with statistical significance(P＜0.05).Conclusion Pharmacological treatment combined with tDCS treatment is effective for sleep disorders and motor function in patients with PD,which could increase the sleep duration and sleep efficiency of PD patients with sleep disorders to a certain extent,reduce the nighttime awakening duration and frequency,thereby improving the fatigue symp-toms during the daytime,and improving the efficacy of conventional pharmacological treatment for PD.