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

In the era of precision medicine,integrating radionuclide-based molecular imaging with targeted internal radiotherapy,integrated theranostics of nuclear medicine emerged as a promising and rapidly advancing field to achieve both visualization and precise treatment of tumors.The advances of commonly used and emerging radiotheranostic agents in oncology were systematically reviewed in this article.

Objective:To explore the feasibility and advantages of applying visualized thermosensitive color-changing bolus in postmastectomy radiotherapy (PMRT) for breast cancer.Methods:Forty patients with breast cancer treated with PMRT in the Second Affiliated Hospital of Soochow University from June 2023 to June 2024 were prospectively selected. They were randomly divided into test and control groups (also referred to as groups A and B, respectively), with 20 patients in each group. Group A, underwent two CT scans: the first scan without bolus (image A1) and the second scan with visualized thermosensitive color-changing bolus (image A2). They were treated with visualized thermosensitive color-changing bolus. Group B also underwent two CT scans: the first scan without bolus (image B1) and the second scan with conventional commercial bolus (image B2), and then were treated with conventional commercial bolus. In the radiotherapy planning, images A1 and A2 were designed as A1-Plan and A2-Plan, and A3-Plan was created by transferring the A1-Plan onto image A2. Images B1 and B2 were designed as B1-Plan and B2-Plan, and B3-Plan was created by transferring the B1-Plan onto image B2. The radiation fields and target optimization functions were identical. The dosimetric differences and skin toxicity reactions between different plans were compared.Results:In Group A, A1-Plan and A2-Plan manifested no statistically significant differences ( P > 0.05) in the doses to organs at risk (OARs), including the ipsilateral lung ( V5 Gy, V10 Gy, V20 Gy), heart ( Dmean), contralateral breast ( Dmean), and skin ( Dmax and Dmean), target homogeneity index (HI), conformity index (CI), prescription dose volume ( V50 Gy), depth of maximum dose ( Dmax), and monitor unit (MU). In Group B, B3-Plan compared to B1-Plan showed reduced V50 Gy (89.9% vs. 95%), HI (0.153 vs. 0.136), and CI (0.817 vs. 0.810), while the two plans displayed no statistically significant differences in doses to OARs. In contrast, A3-Plan and B3-Plan exhibited statistically significant differences ( t = 2.78, 2.29, -0.47, 0.51, 3.13, P < 0.05) in V50 Gy (94.05% vs. 89.90%), Dmax (5 665.4 cGy vs. 5 632.7 cGy), HI (0.148 vs. 0.163), CI (0.83 vs. 0.82), and skin Dmean (5 153.6 cGy vs. 5 048.2 cGy). Compared to the conventional commercial bolus of the same thickness, the visualized thermosensitive color-changing bolus yielded a significantly reduced air cavity volume (3 833 mm 3vs. 21 498 mm 3,t = -9.65, P < 0.05). Both groups experienced only grade I skin toxicity reactions. Conclusions:Compared to the conventional commercial bolus of the same thickness, the visualized thermosensitive color-changing bolus shows a more effective dosimetric distribution in terms of target coverage, HI, and CI, a higher fit to the skin, highly visualized air cavity, and higher positional repeatability in fractionated radiotherapy, demonstrating high practicality and safety.

Objective:To observe the clinical efficacy of subcutaneous row needling at the Foot Motor Sensory Area combined with point application therapy and its influence on defecation-related symptoms.Methods:Seventy eligible patients with poststroke constipation were assigned to an observation group or a control group using the random number table method,with 35 patients in each group.The observation group received subcutaneous row needling at the Foot Motor Sensory Area combined with point application therapy,whereas the control group received lactulose oral solution.After treatment,the total effective rate and safety were compared between the two groups,and changes in the patient assessment of constipation symptom(PAC-SYM),stool form,and constipation symptom scores were observed.Results:The total effective rate was 87.9%in the observation group and 69.7%in the control group,and the difference was statistically significant(P<0.05).No obvious adverse reactions occurred in either group.After treatment,PAC-SYM and constipation symptom scores in both groups were lower than before treatment(P<0.05),with the observation group scoring lower than the control group(P<0.05).After treatment,the Bristol stool form scale(BSFS)score in both groups increased(P<0.05)and approached the score of normal stool form;the difference in the BSFS score between the two groups was not statistically significant(P>0.05).Conclusion:Compared to oral lactulose,subcutaneous insertion with row needling at the scalp Foot Motor Sensory Area combined with point application therapy can better improve poststroke constipation symptoms,shorten both the interval between bowel movements and the duration of each bowel movement,and reduce rectal and abdominal discomfort,with fewer adverse reactions and good safety.

Objective:To evaluate the outcomes of intensive conservative treatment compared to conventional conservative treatment in patients with acute aortic syndrome(AAS).Methods:The study prospectively enrolled consecutive patients with AAS who were admitted to Beijing Anzhen Hospital, affiliated with Capital Medical University, and Beijing Dawanglu Emergency Rescue Hospital from January 2024 to December 2024. These patients with surgical contraindications or refused surgery for various reasons opted for conservative treatment. A total of 282 patients were included, and 15 patients with missing data or those who died without any treatment were excluded. Finally, 267 patients were enrolled, of whom 94 received intensive conservative treatment, and 173 received conventional conservative treatment, the inverse probability of treatment weighting (IPTW) was used to reduce the influence of confoundings. After adjusting of baseline datas via IPTW, the survival outcomes of the two groups were compared at 14 days, 30 days, and at the end of follow-up.Results:The results showed significant differences in acute phase survival rates between the enhanced conservative treatment group and the conventional conservative treatment group at 14 days(82.40%vs.53.20%, P<0.0001). Significant survival differences were also observed at 30 days and at 276-day mid-term follow-up (96.29% vs.51.60%, P<0.0001; 78.50% vs.48.50%, P<0.0001). In the subgroup analysis, for type A aortic dissection, the enhanced conservative treatment group had higher survival rates compared to the conventional conservative treatment group at 14, 30 and 276 days (63.46% vs.41.35%, P<0.05; 52.17% vs.37.90%, P<0.05; 50.00% vs. 31.97%, P<0.05). However, for type B aortic dissection, although the enhanced conservative treatment group had higher survival rates than the conventional conservative treatment group, no statistically significant differences were observed (96.29% vs. 80.00%, P=0.054; 95.65% vs.78.37%, P=0.067; 94.12% vs.74.20%, P=0.088). Conclusion:For patients diagnosed with AAS are forced to choose conservative treatment if emergency surgery is not possible in the first place, intensive conservative treatment strategies can significantly reduce the mortality in the acute phase compared with conventional conservative treatment. Mid-term follow-up, intensive conservative treatment still has a significant survival advantage.

Objective:To investigate the value of carotid，radial and podalic artery intima thickness（CIT，RIT，PIT）combined with monocyte to high-density lipoprotein ratio（MHR）in predicting the severity of coronary artery stenosis in patients with premature coronary artery disease（PCAD）.Methods:A total of 80 patients with PCAD who received treatment in Henan Provincial People's Hospital from October 2023 to May 2024 were prospectively recruited，and they were divided into high group（≥41 score，40 cases）and low group（＜41 score，40 cases）according to the median dichotomy of Gensini score. Thirty-four gender，age and body mass index（BMI）-matched healthy volunteers were selected as the control group. The CIT，RIT，PIT，media and intima media thickness of carotid，radial artery and podalic artery（CMT，RMT，PMT，CIMT，RIMT，PIMT）were measured using 24 MHz ultra-high frequency ultrasound probe，and the ratio of intima to media thickness（CIT/CMT，RIT/RMT，PIT/PMT）was calculated. The differences of general clinical data，laboratory indexes and ultrasonic parameters among the three groups were compared. Risk factors affecting the severity of coronary stenosis in PCAD patients were explored by binary logistic regression. Subject working characteristic curves were plotted，area under the curve（AUC）was calculated，and the values of each ultrasound parameter and MHR in the independent and combined diagnosis of the severity of coronary artery stenosis in PCAD patients were evaluated.Results:①There were no statistically significant differences in age，gender，BMI，total cholesterol，CMT，RMT and PMT among the three groups（all P＞0.05）. There were no statistically significant differences in the comparison of smoking，hypertension，diabetes mellitus，systolic blood pressure，diastolic blood pressure，low-density lipoprotein cholesterol，total cholesterol，and triglycerides between the two subgroups of the PCAD（all P>0.05）. ②CIT，CIMT，CIT/CMT，RIT，RIMT，RIT/RMT，PIT，PIMT，PIT/PMT were thickened in the high group compared with the low group，and MHR was higher than in the low group（all P<0.05），the differences in the above parameters remained statistically significant when comparing the PCAD group with the control group（all P<0.05）. ③The AUC values for MHR，CIT，RIT and PIT alone to predict the severity of coronary stenosis in patients with PCAD were 0.781，0.767，0.780 and 0.722，respectively. The combined diagnostic efficiency of the four parameters was better than the independent diagnostic efficiency（AUC = 0.885）. Conclusions:CIT，RIT and PIT are thicker in PCAD patients with high Gensini score and the combination of artery intima thickness and MHR has good efficacy in predicting the severity of coronary artery stenosis in PCAD patients.

Objective:To evaluate the changes of carotid intima thickness（CIT）and stiffness parameters in ankylosing spondylitis（AS）patients by 24 MHz ultra-high frequency ultrasound probe and RF-data based quantitative analysis on vessel stiffness（R-VQS），and to explore its influencing factors.Methods:Sixty patients with AS who underwent consultation at Henan Provincial People's Hospital from November 2023 to May 2024 were prospectively collected as AS group，54 healthy volunteers matched for sex，age，and body mass index were collected as control group. CIT were measured using a 24 MHz ultra-high frequency ultrasound probe，hardness coefficien（HC）and pulse wave velocity（PWV）were measured by R-VQS，the differences of the parameters between the two groups were compared. The changes of carotid artery elasticity and intima thickness and their influencing factors in patients with AS were explored by univariate and multivariate linear regression analysis.Results:①C-reactiveprotein，erythrocyte sedimentation rate（ESR），neutrophil count and neutrophil to lymphocyte ratio（NLR）were elevated in the AS group compared with the control group，and the differences were statistically significant（all P < 0.05）. ②CIT，carotid intima-media thickness（CIMT），HC，PWV and epicardial adipose tissue thickness（EATT）were all increased in the AS group compared with the control group，and the differences were statistically significant（all P < 0.05）. ③Multifactorial linear regression analysis showed that EATT，ESR were the main influencing factors of HC，PWV and CIT（ β=2.192，0.031；1.792，0.002；0.097，0.001；all P＜0.05）. Conclusions:Carotid CIT，CIMT，HC，PWV and EATT are all higher in the AS patients，and ESR and EATT are the main influencing factors of HC，PWV，and CIT，suggesting that more attention should be paid to the detection of ESR and EATT in patients with AS when interventions are performed clinically.

With the full implementation of the Diagnosis Related Groups(DRG)payment model,its institutional advantages in optimizing resource allocation and controlling medical costs through fixed disease payment standards have gradually emerged.However,it has also triggered structural value conflicts in the doctor-patient relationship.Based on the four principles of medical ethics,this paper constructed an analytical framework for the value conflicts in doctor-patient relationships under the DRG payment model.Starting from the manifestations of value conflicts,the inducements creating them were analyzed in depth.On these foundations,multi-dimensional optimization paths were proposed,including repairing respect-related conflicts through information transparency and decision-making co-governance;constructing a refined cost management system and embedding an ethical review mechanism to resolve non-harm conflicts;implementing a phased payment mechanism for innovative technologies and an ethical review exemption mechanism to alleviate benefit conflicts;as well as designing dynamic payment rules,unifying payment standards for insurance participation types,and strengthening dynamic monitoring to address justice conflicts.Under this framework,this paper aimed to promote the gradual transformation of DRG from a cost-control tool to a governance tool.While ensuring the security of the fund,it was necessary to maintain the bottom line of quality,stimulate technological innovation,and return to the patient-centered concept,thereby promoting the doctor-patient relationship to shift from a zero-sum game to a symbiotic and win-win situation.

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.