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 evaluate the development of fetal cerebral sulci and gyrus and the blood perfusion in pregnant women with gestational diabetes mellitus(GDM) by ultrasound.Methods:A total of 1 540 pregnant women with 28-34 weeks of pregnancy who underwent systematic screening in Henan Provincial People′s Hospital from January 2022 to October 2022 were prospectively selected, 100 pregnant women with GDM were selected as the GDM group. According to the effect of blood glucose control, the GDM group was divided into 2 groups: the satisfied control group (GDM group 1), and the dissatisfied control group (GDM group 2), with 50 cases in each group. At the same period, 50 healthy pregnant women at 28-34 weeks of gestation were enrolled as the control group. The differences of the sylvian fissure, parietooccipital sulci, calcarine sulci and cinguli sulci among the 3 groups were statistically analyzed. And the correlations between the deep of the brain cerebral sulci and gyrus and controlled blood glucose levels were evaluated. The umbilical artery pulsation index(UAPI), middle cerebral artery pulsation index(MCAPI) and ductus venosus pulsation index(DVPI) among the 3 groups were compared, and the differences in fetal blood perfusion among the 3 groups were evaluated.Results:There were no significant differences in the depths of the sylvian fissure, parietooccipital sulci, calcarine sulci and cinguli sulci between the control group and the GDM group 1 (all P>0.05), and they were larger than those of the GDM group 2 (all P<0.05). The depths of lateral fissure, parieto-occipital sulcus, cingulate sulcus and calcarine sulcus were negatively correlated with fasting blood glucose, 1 h and 2 h postprandial blood glucose (all P<0.05). There were no significant differences in MCAPI, UAPI and DVPI between the control group and GDM1 group (all P>0.05). The MCAPI in GDM 2 group was lower than that in the control group and GDM 1 group, and the UAPI and DVPI values were higher than those in the control group and GDM1 group(all P<0.05). Conclusions:The maturity of fetal cerebral sulci and gyrus in GDM pregnant women is related to the blood glucose control of pregnant women. The change of blood perfusion caused by persistent hyperglycemia in pregnant women and intrauterine hypoxia may cause the development retardation of cerebral sulci and gyrus.

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.

Ferroptosis is a new programmed cell death dependent on iron ions.Ferroptosis can be induced by endogenous or exogenous pathways,and cells exhibit specific cell morphological signs and are regulated by a variety of molecular mechanisms.In recent years,more and more studies have shown that ferroptosis plays an important role in the treatment of cancer.This article summarizes the mechanism of ferroptosis in bladder cancer and the regulation of cancer cells,as well as the role of ferroptosis-related factors,non-coding RNA regulation,N6-methyladenosine(m6A),amino acid metabolism and autophagy dependent ferroptosis in the growth and proliferation of bladder cancer,with a view to provide new strategies for the treatment of bladder cancer.

Objective To explore the value of one-stop spectral CT scanning of computer tomography pulmonary angiography(CTPA)combined with abdominal-pelvic enhancement in preoperative evaluation for patients with gynecological tumors.Methods Ninety-six patients with gynecological tumors who received both spectral CTPA and abdominal-pelvic enhanced CT examination at Zhongshan Hospital(Xiamen Branch),Fudan University,between January 2022 and December 2023 were collected.The conventional scanning group(n=48)received two independent spectral CT scans with twice contrast injections,while the one-stop scanning group(n=48)received one-stop spectral CTPA and abdominal-pelvic enhancement with once contrast injection.Virtual monochromatic images(VMIs)at 65 keV for CTPA,50 keV VMIs for abdominal-pelvic enhancement,contrast-enhanced iodine maps and effective atomic number images for the two parts were generated for all patients.The scanning parameters such as contrast agent dose,scanning duration,objective parameters of the images(CT values,iodine concentration,effective atomic number,etc.),as well as overall image quality score,the confidence score in diagnosing pulmonary embolization(PE),and the conspicuity of gynecological tumors were compared between the two groups.Results A total of 24 cases(25% )of PE were found in 96 patients.Compared with the conventional scanning group,the one-stop scanning group showed a significant reduction in contrast agent dosage([62.88±3.59]mL vs[98.52±2.63]mL,P＜0.001)and scan duration([95.94±0.38]s vs[108.91±0.35]s,P＜0.001).There was no statistically significant difference in dose length product(DLP),volume CT dose index,and effective dose(ED)between the two groups.There was no statistically significant difference in objective parameters and subjective image scores between the two groups of patients'CTPA images,abdominal and pelvic CT plain scans,and enhanced images.All image scores were≥3 points,meeting the diagnostic requirements.There was no statistically significant difference of confidence score in diagnosing PE and the ability to display tumor lesions between the two groups.Conclusions In comparison to conventional scanning,one-stop spectral scanning provides comparable image quality,confidence in diagnosing PE,and the conspicuity of gynecological tumors under a lower contrast agent dosage,a shorter scanning time,and a less patient waiting time in the preoperative evaluation for patients with gynecologic tumors,which is highly valuable.

Objective:To investigate the clinical effect of jujube core-shaped tissue resection technique in the treatment of alar reduction.Methods:A retrospective analysis was performed for the clinical data of patients who underwent alar reduction from February 2019 to June 2022. A spindle-shaped incision line was designed along the outer edge of the base of the nasal lobule, with a width of 4-5 mm and a length of 8-12 mm. The incision line was 1-2 mm away from the alar groove, and the inner side of the design line was extended to the inside of the nasal vestibule. After the incision was made, the subcutaneous tissue was undermining dissected with curved sharp scissors, and the shape of the extended excision tissue was similar to that of jujube core. After reduction, the incision was closed with vertical mattress suture. The surgical effect and complications were followed up after surgery, and an independent attending plastic surgeon evaluated the outcome and scarring based on photos before and at the last postoperative follow-up using the global aesthetic improvement scale (GAIS) and the Vancouver scar scale (VSS). GAIS is graded as 1, 2, 3, 4, and 5 points, and the lower the score, the better the improvement(≤3 points as effective improvement). VSS includes four parameters: color (0-3 points), thickness (0-4 points), vascular distribution (0-3 points), and softness (0-5 points). The higher the score, the more significant the scar is.Results:A total of 20 patients were enrolled, including 6 males and 14 females, aged 20 to 33 years, with an average age of 24.9 years. Before the operation, there were different degrees of alar flare and alar hypertrophy. After surgery, 13 patients had mild swelling, ecchymosis, which resolved after 3 days. There were no major complications as infection, incision dehiscence, and delayed healing. After 3 to 16 months of postoperative follow-up, 2 patients gradually developed cartilage deformation and affected the appearance of the nostrils 6 to 9 months after surgery due to the combination of rib-based rhinoplasty, and the satisfactory results were obtained after revision surgery. The symmetry of the nostrils was significantly improved. The GAIS score of 20 patients was (1.20±0.41) points, of which, 16 patients were rated as 1 point and 4 patients were rated as 2 points, all of which met the improvement criteria, and the VSS score was (1.45±0.60) points, in which the average score for color, thickness, vasculature and compliance are 0.60, 0.05, 0.55 and 0.30 points respectively.Conclusion:The application of jujube core-shaped tissue resection technique for alar reduction can increase the amount of tissue removal with the same incision width, which can not only fully narrow the alar effectively but also correct the hypertrophy of the alar tissue.

Objective:To investigate the clinical outcome of biplanar botulinum toxin type A injection in alleviating platysmal bands.Methods:From November 2022 to May 2023, the clinical data of patients with platysmal bands treated by botulinum toxin type A injection in Department of Face and Neck Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, and Department of Plastic Surgery, Chengdu Badachu Cosmetic Hospital were retrospectively analyzed. The platysmal bands were marked, while patients were grinning, before injection. Using a 13 mm 30 G needle, 20 U/ml botulinum toxin was injected into the muscle layer along the bands from the clavicle direction. The dose was 1 U at a single point every 1.5 cm. Using a 3 mm 30 G needle, 10 U/ml botulinum toxin was injected into the deep surface of dermis along the bands with a single point dose of 0.5 U. Effects were evaluated by overall subjective satisfaction of patients, which were categorized into 4 grades: very satisfied, satisfied, dissatisfied, very dissatisfied. In addition, accessment by a third-party physician with global aesthetic improvement scale (GAIS) (1-5 points, the lower the score, the more significant the improvement is) and Geister platysmal band scale (0-4 points, the higher the score, the more severe the platysmal band is). Normal distribution data was represented by Mean±SD.Results:A total of 19 patients were included, including 3 males and 16 females, with the average age of 36.1 years. After a mean follow-up of 1.3 months (1-5 months), the overall subjective satisfaction was 100%(19/19). The GAIS score of third-party physicians was 1.12±0.33. 100%(19/19) of patients received a rating over moderate improvement(significant improvement in 17 cases and moderate improvement in 2 cases). The Geister platysmal band score decreased from preoperative 3.65 ± 0.33 to postoperative 0.76 ± 0.44. No serious complications were found except 5 cases of local congestion and 2 cases of injection pain, which were relieved in 1 week and 3 hours respectively. 2 cases felt mild neck weakness, but neck activity was not affected. The adverse symptoms all completely resolved spontaneously within 4 weeks. All patients have no mouth deviation, difficulty speaking, facial paralysis, allergies, or other noticeable complications.Conclusion:The injection of botulinum toxin type A in dual-plane of platysmal intramuscular layer and deep intradermal layer can effectively alleviate platysmal bands and achieve neck rejuvenation.