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 study and design one kind of flash radiotherapy(Flash-RT)equipment with ultra-high dose rate,which can be used in the mechanism research of Flash-RT with ultra-high dose rate.Methods:Based on the technique roadmap of high-power petal accelerator,the Flash-RT equipment can realize the requirement of Flash-RT for ultra-high dose rate and multiple irradiation angles.The corresponding design and research work were carried out on the basis of the overall design of the equipment,the main components and characteristics,the dynamics design of beam,the construction of movable and preliminary experimental platform,etc.Result:The dose rate of the designed equipment can reach to 100 Gy/s at a distance of 0.8 meters from the target point,which is easy to realize the radiotherapy method with multi angles.Conclusion:The designed X-ray equipment based on the technique roadmap of high-power petal accelerator can realize the research for the mechanism of medical Flash-RT equipment with ultra-high dose rate.

The establishment of an economic operating mechanisms for hospitals is a key factor in advancing the growth of public hospitals in the modern age.At present,the due value of key factors such as medical resources and labor value of medical personnel in public hospitals in China has not been fully reflected,which not only restricts the overall operation efficiency of hospitals,but also makes it difficult to realize the marginal value of hospital operation and management.The economic operating mechanisms of public hospitals is in urgent need of reform.Large public hospitals in Henan Province has established an economic operating mechanisms of public hospitals based on intelli-gent finance,comprehensive budget management as the core,and cost control and performance management as the major tools to realize the interconnection of various systems and promote the high-quality development of hospi-tals with the three major supports of industry and finance integration,financial integration and financial integration.

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.

BACKGROUND:Abnormal extracellular matrix accumulation and excessive proliferation of fibroblasts are the main manifestations of pathological scars.Excessive proliferation of fibroblasts leads to the production of large amounts of collagen-based extracellular matrix.Therefore,to investigate the role of fibroblast fibrosis in the formation of pathological scar will provide a new idea for revealing the mechanism of pathological scar and biological therapy. OBJECTIVE:To investigate the effect of RAS-selective lethal small molecule 3(RSL3)on the fibrosis of human pathological scar fibroblasts. METHODS:Then cases of pathological scar tissue and normal skin tissue samples from the same individuals,provided by the Department of Burn Plastic Surgery,General Hospital of Ningxia Medical University,were collected.Fibroblasts of human pathological scar and human normal skin were extracted and used in the following experiments.The general condition of the pathological scar tissue and the normal skin tissue was detected by hematoxylin-eosin staining.The appearance of fibroblasts from pathological scar and normal skin were observed by inverted microscope.The fibroblasts were verified by immunofluorescence assay.The cells were treated with different concentrations of RSL3(1,3,5,7,9,11,13 μmol/L).The inhibitory concentration of RSL3 on fibroblasts was detected by cell counting kit-8.Control group(without treatment)and RSL3 intervention group(treated with 7 μmol/L RSL3 for 24 hours)were set up.The mRNA and protein expressions of glutathione peroxidase 4,type Ⅰ collagen,type Ⅲ collagen and α-smooth muscle actin were detected by Qrt-PCR and western blot,respectively.Level of malondialdehyde in cells was detected.The residual scratch area was measured by cell scratch test after 24 hours to calculate the percentage of residual scratch area. RESULTS AND CONCLUSION:The expression of glutathione peroxidase 4 in the pathological scar group was higher than that in the normal skin group(Mrna:t=3.252,P<0.01;protein:t=5.075,P<0.01).The expression of glutathione peroxidase 4 in the pathological scar fibroblast group was higher than that in the normal skin fibroblast group(Mrna:t=10.32,P<0.01;protein:t=26.22,P<0.01).Compared with the control group,the expression of glutathione peroxidase 4 was decreased(Mrna:t=2.798,P<0.05;protein:t=4.643,P<0.01),the content of malondialdehyde was increased(t=2.917,P<0.05),the expression of type Ⅰ collagen(Mrna:t=15.84,P<0.01;protein:t=4.610,P<0.01),type Ⅲ collagen(Mrna:t=28.86,P<0.01;protein:t=7.713,P<0.01)and α-smooth muscle actin(Mrna:t=2.671,P<0.05;protein:t=7.417,P<0.01)were decreased in the RSL3 intervention group.Compared with the control group,the migration ability was weakened in the RSL3 intervention group(t=14.06,P<0.01).To conclude,RSL3 can inhibit the expression of glutathione peroxidase 4 and then inhibit the ability of fibrosis and migration of pathological scar fibroblasts.

Multiple primary lung cancer(MPLC)refers to patients with two or more primary lesions of lung cancer.It can be divided into synchronous MPLC(sMPLC)and metachronous MPLC(mMPLC)based on the timing of occurrence.In recent years,the detection rate of MPLC has gradually increased.However,considerable controversy exists in distinguishing MPLC from intrapulmonary metastasis(IM),especially when the histopathological types are identical.Given the significant differences in treatment strategies and prognosis in clinical practice currently,accurate diagnosis of MPLC is cru-cial for personalized precision therapy.Molecular genetics and sequencing technologies offer effective strategies for assessing the clonal origin of tumors.There have been reports of coexisting mutations in the epidermal growth factor receptor(EGFR)and anaplastic lymphoma kinase(ALK)fusion genes in non-small cell lung cancer,but case of EGFR mutation following an ALK mutation has not been mentioned.This article accurately diagnoses and retrospectively analyzes the clinical data of a case of ALK mutant adenocarcinoma in a male patient who developed an EGFR mutation with multiple metastases four years after surgery,and reviews the relevant literature.This paper aims to deepen the understanding of mMPLC and provide clinical refer-ences for the diagnosis and treatment of such patients.

The clinical and genetic characteristics of the family reported with neurodevelopmental syndrome caused by the SPTBN1 gene mutation were analyzed for clinical diagnosis.The proband was a boy, 2 years and 3 months old, admitted to the Department of Neurology, Guangzhou Women and Children′s Medical Center in June 2022 with comprehensive developmental delays as the main manifestation.The boy was backward in development since childhood.He was able to raise his head at the age of 3 months and sit alone at the age of 11 months.He could stand up with support but was unable to climb.He occasionally spoke polysyllabic words.The proband′s elder brother, 3 years and 1 month old, was able to walk at the age of 1 year and 6 months, and could speak " Mom and Dad" consciously and understand some instructions.He liked to play with other children.The mother of the proband was mentally retarded, while the father and grandparents of the proband had no symptoms.The proband was found to have a heterozygous mutation of the SPTBN1 gene (NM_003128.3), c.811G>A (p.Val271Met).The proband′s mother and elder brother also had a heterozygous mutation, which, however, was not detected in the proband′s father.The neurodevelopmental syndrome caused by the SPTBN1 gene mutation is rare in China, which can be manifested as language and motor delays and intellectual disabilities from early childhood, and individuals with the same genetic variation show different clinical phenotypes.

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.

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.