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 evaluate the treatment strategies and outcomes for contracted nasal deformity.Methods:A retrospective review was conducted of the patients with contracted noses who underwent surgery at the Department of Plastic and Aesthetic Surgery, the Second Xiangya Hospital of Central South University, between January 2021 and January 2024. Based on the pathologic-anatomic features and severity of the deformity, patients were categorized as having mild, moderate or severe contraction. Mild cases received extensive subcutaneous dissection and framework reconstruction with various grafts. Moderate cases underwent preoperative nasal-skin distraction and intra-operative reconstruction with lower lateral or septal cartilage. Severe cases, in addition to reconstruction of the lower lateral cartilage and nasal septum, underwent individualized repair, including mucosal or cutaneous defect resurfacing. Postoperative follow-up assessed nasal appearance, complications and recurrence of contraction. Nasal aesthetics were quantified with visual analogue scale (VAS, 0-10 points; higher scores = less deformity), and patient satisfaction with the rhinoplasty outcome evaluation (ROE) questionnaire (0 = very dissatisfied, 100 = very satisfied) before surgery and at final follow-up. Paired t-test was used for VAS and ROE comparisons; categorical variables were analyzed with the χ2 test. A P-value < 0.05 denoted statistical significance. Results:A total of 96 patients were included, comprising 7 males and 89 females, aged (27.4 ± 8.0) years (19-58 years). There were 64 cases of mild, 19 cases of moderate, and 13 cases of severe contracted nose deformities. Postoperative follow-up(14.0 ± 4.6) months (6-19 months). No cases of abnormal nasal appearance, infection, necrosis, scar hyperplasia, or recurrence of contracted nose were observed during follow-up. Significant improvements in nasal aesthetic outcomes were observed. The VAS scores for mild, moderate, and severe contracted noses increased significantly from preoperative values of 4.7 ± 1.0, 3.0 ± 1.2, and 2.2± 1.1 to postoperative values of 8.6 ± 0.7, 8.9 ± 0.7, and 8.2 ± 0.9, respectively (all P < 0.01). Similarly, the ROE scores improved significantly from 59.1 ± 10.0, 34.2 ± 12.1, and 28.5± 6.3 preoperatively to 90.2 ± 9.5, 91.5 ± 7.5, and 93.3 ± 5.8 postoperatively (all P < 0.01). Conclusion:Selecting appropriate surgical methods based on the pathological and anatomical characteristics and severity of contracted nose deformities can achieve favorable outcomes. Postoperative nasal aesthetic appearance is significantly improved, and patient satisfaction is high.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To analyze the occurrence and risk factors of needlestick and sharps injuries(NSIs)among oral health care workers(HCWs).Methods NSIs reported by West China Hospital of Stomatology from 2020 to 2023 were collected,and factors relevant to NSIs were analyzed.Results A total of 391 cases of NSIs were repor-ted.Only one case of injury was caused by a sterile device,while the remaining 390 cases were caused by contamina-ted devices.There were 85,107,113,and 86 cases in 2020,2021,2022,and 2023,respectively.Most NSIs oc-curred among interns(n=235,60.1％).294 cases(75.2％)of NSIs occurred among HCWs who had less than 3 years of clinical experience.The distribution of NSIs among 235 interns in different months showed that NSIs ac-counted for a relatively high proportion from April to June and July to September,and the difference was statistica-lly significant(P＜0.05).The ventral side of the left thumb was the most common site of NSIs(n=53,13.6％),followed by the ventral side of the right index finger(n=45,11.5％)and the ventral side of the left index finger(n=44,11.3％).The most common devices involved in NSIs were various types of syringe needles(n=84,21.5％),followed by various types of dental burs(n=76,19.4％)and suture needles(n=49,12.5％).Injuries mainly oc-curred during the treatment process(n=212,54.2％)and in the department of endodontics(n=86,22.0％).This study didn't find any occupational bloodborne infection case caused by NSIs.Conclusion NSIs mainly occur among inexperienced oral interns,and devices causing NSIs are related to the treatment process.

ObjectiveTo analyze the evolutionary characteristics and genetic variations of the HA (hemagglutinin) and NA (neuraminidase) genes of influenza A(H1N1) viruses in Shanghai during 2024, to investigate their transmission patterns, and to evaluate their potential impact on vaccine effectiveness. MethodsFrom January to October 2024, throat swab specimens were collected from influenza like illness (ILI) patients at 4 hospitals in Shanghai. Real-time fluorescence ploymerase chain reaction (RT-PCR) was used for virus detection and isolation of H1N1 influenza viruses. Forty influenza A(H1N1) virus strains were sequenced using Illumina NovaSeq 6000 platform, followed by phylogenetic analyses, genetic distance analysis, and amino acid variation analyses of HA and NA genes. ResultsPhylogenetic tree of the HA and NA genes revealed that the 40 influenza A(H1N1) virus strains circulating in Shanghai in 2024 exhibited no significant geographic clustering, with a broad origin of strains and complex transmission chains. Genetic distance analyses demonstrated that the average intra-group genetic distances of HA and NA genes among the Shanghai strains were 0.005 1±0.000 6 and 0.004 6±0.000 6, respectively, which were comparable to or higher than those observed in global surveillance strains. Both HA and NA genes displayed frequent mutations. Compared to the 2023‒2024 and 2024‒2025 Northern Hemisphere A(H1N1) vaccine strains (WHO-recommended), the HA proteins of 40 Shanghai strains exhibited amino acid substitutions at positions 120, 137, 142, 169, 216, 223, 260, 277, 356 and 451, with critical mutations at positions 137 and 142 located within the Ca2 antigenic determinant. Furthermore, mutations in the NA protein were observed at positions 13, 50, 200, 257, 264, 339 and 382. ConclusionThe genetic background of the 2024 Shanghai influenza A(H1N1) virus strains is complex and diverse, and antigenic variation may affect vaccine effectiveness. Therefore, it is recommended to enhance genomic surveillance of influenza viruses, evaluate vaccine suitability, and implement more targeted prevention and control strategies against imported influenza viruses.

Objective To explore the effect of PCSK9 inhibitor combined with atorvastatin on carotid atherosclerosis and its anti-inflammatory effect in patients with hypertension complicated with type 2 diabetes mellitus.Methods A total of 100 patients with hypertension complicated with type 2 diabetes mellitus who were treated in Nanchang Third Hospital from October 2022 to August 2023 were selected as the research subjects.They were divided into the control group and the study group by the random number table method,with 50 cases in each group.Both groups of patients received conventional antihypertensive,hypoglycemic,and antiplatelet therapy.The control group took 20 mg of atorvastatin calcium tablets orally,once a night.On the basis of the control group,the study group was additionally given 150 mg of evolocumab injection(a PCSK9 inhibitor)by subcutaneous injection,once every two weeks.Both groups of patients were followed up for 24 weeks.The levels of blood lipids,blood glucose,inflammatory cytokines,carotid intima-media thickness(IMT),atherosclerotic plaque score and adverse reactions of the patients in the two groups before and after treatment were detected and compared.Results The levels of TC,TG and LDL-C in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜0.05).The levels of IL-1,IL-6,TNF-α,hs-CRP,as well as the ca-rotid IMT and atherosclerotic plaque score in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜O.05).During the treatment period,there was no significant difference in the occurrence of adverse reac-tions between the two groups(P＞0.05).Conclusion The combination of PCSK9 inhibitor and atorvastatin can effectively regulate the blood lipid levels of patients with hypertension complicated and type 2 diabetes mellitus,alleviate the inflammatory response,and improve the degree of carotid atherosclerosis in these pa-tients.

Objective To initially explore the possibility of applying the fluorescence micro-optical sectioning tomography(fMOST)high-resolution 3D reconstruction system to the morphological study of the intestinal nervous system and to preliminarily establish a method for studying the morphology of the intestinal nervous system using this system.Methods fMOST high-resolution 3D reconstruction system was used to study the intestinal nervous system of C57BL/6 mice in detail.Based on this method,a new morphological method of the visceral nervous system of small animal models was explored at the single-cell level.Results Compared with the large intestine,the small intestine lacked the typical myenteric plexus(Auerbach),deep mucosal plexus(Henley),and submucosal superficial plexus(Meissner).Conclusion The result of this paper provide a clearer and systematic display of the anatomical structure of the enteric nervous system in C57BL/6 mice,and further clarify the similarities and differences between the enteric nervous system of mice and human,and provide a theoretical basis for its rational application in the study of digestive system diseases.The morphological study of fMOST high-resolution 3D reconstruction system is not limited to the central nervous system,but can be extended to the morphological study of multiple visceral nervous systems.

Lung transplantation is an important means to treat end-stage lung disease and improve the survival rate and quality of life of patients. However, many postoperative complications seriously affect the prognosis of recipients. Accurate identification of key prognostic factors and construction of individualized and accurate prediction models are of great significance for postoperative prognosis evaluation, treatment strategy formulation and clinical decision-making. In recent years, the clinical prediction model of lung transplantation has gradually changed from traditional statistical methods to machine learning-driven. Compared with traditional models such as Cox regression and Logistic regression, machine learning models such as random forest, support vector machine and artificial neural network have certain advantages in postoperative survival rate prediction, early warning of complications and pulmonary function evaluation. However, their application is also affected by insufficient sample size and poor interpretability of models. Under the condition of small samples, the traditional model still has important value in prediction accuracy. The appropriate prediction model should be selected according to the clinical status of lung transplantation in China, considering the factors such as sample size, variable complexity and model interpretability. In the future, a multi-center, large-sample lung transplantation database should be constructed to further optimize and tap the potential of machine learning algorithms to improve the robustness and clinical applicability of the model.

Objective:To explore the clinical efficacy of Wenshen Chushi Decoction combined with low intensity pulsed ultra-sound(LIPUS)on erectile dysfunction(ED)caused by renal deficiency and phlegm-dampness syndrome.Methods:One hundred and twenty ED patients were included from the Department of Andrology in the First Hospital of Hunan University of Traditional Chinese Medicine.The patients in control group were treated with Wenshen Chushi Decoction.While the patients in observation group were trea-ted with Wenshen Chushi Decoction combined with LIPUS for 8 consecutive weeks.After the treatment,the efficacy was evaluated using the International Index of Erectile Function-5(IIEF-5)score,Penile Flow Index(PFI),Traditional Chinese Medicine Syndrome Score,Self-Rating Depression Scale(SDS)score,and Self-Rating Anxiety Scale(SAS)score.Safety was also observed.And the ef-ficacy was followed up 4 weeks after the end of treatment.Results:Fifty-seven cases were enrolled into control group finally with 55 cases in the treatment group.After the treatment,all the patients in both of groups showed an improvement in IIEF-5 scores(P＜0.01).Compared with the control group(19.09±2.22),the IIEF-5 score in observation group(20.42±2.39)increased signifi-cantly(P＜0.01).After the treatment,the scores of PFI,TCM syndrome and SDS in both groups decreased(P＜0.01,P＜0.05,P＜0.01).Compared with the control group([3.77±1.21],[9.91±1.71]and[39.88±2.63]points),the observation group([2.92±1.08],[4.78±1.45],and[34.51±2.09]points)showed a more significant decrease(P＜0.01).There was no significant difference in total effective rate between the two groups(P＞0.05).During follow-up,the IIEF-5 scores of both groups of patients were higher than those before(P＜0.05,P＜0.01),and the observation group score was higher than that in the control group([17.15±3.37]vs[13.63±1.96],P＜0.01).No adverse reaction and abnormality of indicators occurred in both of two groups.Conclusion:Wenshen Chushi Decoction has a significant therapeutic effect on ED caused by renal deficiency and phlegm-dampness syndrome.It can not only improve the quality of erection,but also improve the physical and mental symptoms associated with ED,which makes therapeutic effect lasting longer.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.