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 clinical efficacy of proximal femoral reconstruction osteotomy (PFRO) in hip revision arthroplasty.Methods:A retrospective analysis was conducted of the 92 patients (93 hips) who had undergone PFRO in hip revision arthroplasty at Department of Orthopedics, The First Affiliated Hospital, University of Science and Technology of China from January 2019 to December 2023. The cohort included 50 males (51 hips) and 42 females (42 hips), with an age of (64.5±11.7) years and a body mass index of (23.7±2.9) kg/m 2. Surgical procedures were performed under general anesthesia via a posterolateral approach. Biologic prostheses were used in femoral reconstruction, and PFRO fragments repositioned and fixed using cerclage wires. The data collected were operative time, intraoperative blood loss, length of osteotomy fragments, healing at the osteotomy site, intraoperative and follow-up complications, as well as Harris hip score (HHS) and leg length discrepancy (LLD) at the last follow-up. Results:For this cohort, operative time was (174.9±45.6) minutes, intraoperative blood loss (594.6±206.6) mL, and length of osteotomy fragments (12.3±2.3) mm. The 92 patients were followed up for (35.8±12.3) months. For them, HHS improved from preoperative (38.3±8.5) points to (80.5±12.8) points at the last follow-up, and LLD decreased from preoperative (21.2±13.0) mm to 2.0(0.0, 5.0) mm at the last follow-up, showing significant differences ( P<0.05). The osteotomy sites healed in 89 cases (90 hips), with a displacement of the greater trochanter <5 mm; 3 cases (3 hips) experienced nonunion with wire loosening and a displacement of the greater trochanter >10 mm. The osteotomy fragment of the greater trochanter got fractured in 2 patients (2 hips) and a fracture of the medial cortex of the proximal femur occurred in 11 patients (11 hips), but follow-ups observed healing of all the fractures. One patient (1 hip) developed postoperative posterior dislocation of the hip which was treated conservatively. One patient (1 hip) developed postoperative periprosthetic infection which did not recur after twice of debridement followed by prosthetic revision of the proximal femoral tumor. Conclusion:In hip revision arthroplasty, as PFRO demonstrates a low incidence of fragment fractures of the greater trochanter and a high rate of healing at the osteotomy site, its short-term clinical outcomes are satisfactory.

Objective:To analyze the risk of re-displacement after external fixation treatment for distal radius fractures in older adult patients and establish a nomogram model.Methods:A retrospective analysis was conducted on the clinical data of 96 older adult patients with distal radius fractures who were treated with external fixation at Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from January to December 2022. Based on whether re-displacement of the fracture occurred, the patients were divided into an observation group (re-displacement occurred, n = 15) and a control group (no re-displacement occurred, n = 81). Univariate and logistic regression analyses were used to identify risk factors, and a nomogram model was established. Results:There were statistically significant differences between the two groups in terms of age ( t = 2.13, P = 0.036), sex ( χ2 = 4.17, P = 0.041), presence of comminution ( χ2 = 14.18, P < 0.001), fracture type ( χ2 = 49.59, P < 0.001), body mass index ( t = 3.01, P = 0.003), number of adjustments to external fixation ( χ2 = 4.17, P = 0.041), presence of bone resorption or necrosis ( χ2 = 13.96, P < 0.001), appropriateness of external fixation management ( χ2 = 21.43, P < 0.001), and reasonableness of functional exercise ( χ2 =23.67, P < 0.001). Independent risk factors for the occurrence of re-displacement after external fixation treatment for distal radius fractures in older adult patients included age ( OR = 3.07, P = 0.002), sex ( OR = 3.11, P = 0.007), presence of comminution ( OR = 2.56, P = 0.039), presence of bone resorption or necrosis ( OR = 5.70, P < 0.001), and reasonableness of functional exercise ( OR = 3.04, P < 0.001). The discrimination analysis of the nomogram model showed an area under the curve of 0.855, with a 95% CI of 0.853 to 0.927, and a critical value of 31.25% ( P < 0.001). The GiViTI calibration curve showed that the 80%-90% confidence intervals did not cross the 45° bisector in the graph ( P > 0.05). The Hosmer-Lemeshow goodness-of-fit test showed no statistically significant difference ( χ2 = 5.29, P = 0.582). The decision curve analysis indicated that when the risk of re-displacement exceeded 33.64% in older adult patients undergoing external fixation for distal radius fractures, the net benefit of intervening in these patients was maximized. Conclusions:Age, sex, presence of comminution, presence of bone resorption or necrosis, and the reasonableness of functional exercise are independent risk factors for re-displacement after external fixation treatment of distal radius fractures in older adult patients. The higher the score on the nomogram model, the greater the risk of fracture re-displacement in the patient.

Objective:To analyze the risk of re-displacement after external fixation treatment for distal radius fractures in older adult patients and establish a nomogram model.Methods:A retrospective analysis was conducted on the clinical data of 96 older adult patients with distal radius fractures who were treated with external fixation at Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from January to December 2022. Based on whether re-displacement of the fracture occurred, the patients were divided into an observation group (re-displacement occurred, n = 15) and a control group (no re-displacement occurred, n = 81). Univariate and logistic regression analyses were used to identify risk factors, and a nomogram model was established. Results:There were statistically significant differences between the two groups in terms of age ( t = 2.13, P = 0.036), sex ( χ2 = 4.17, P = 0.041), presence of comminution ( χ2 = 14.18, P < 0.001), fracture type ( χ2 = 49.59, P < 0.001), body mass index ( t = 3.01, P = 0.003), number of adjustments to external fixation ( χ2 = 4.17, P = 0.041), presence of bone resorption or necrosis ( χ2 = 13.96, P < 0.001), appropriateness of external fixation management ( χ2 = 21.43, P < 0.001), and reasonableness of functional exercise ( χ2 =23.67, P < 0.001). Independent risk factors for the occurrence of re-displacement after external fixation treatment for distal radius fractures in older adult patients included age ( OR = 3.07, P = 0.002), sex ( OR = 3.11, P = 0.007), presence of comminution ( OR = 2.56, P = 0.039), presence of bone resorption or necrosis ( OR = 5.70, P < 0.001), and reasonableness of functional exercise ( OR = 3.04, P < 0.001). The discrimination analysis of the nomogram model showed an area under the curve of 0.855, with a 95% CI of 0.853 to 0.927, and a critical value of 31.25% ( P < 0.001). The GiViTI calibration curve showed that the 80%-90% confidence intervals did not cross the 45° bisector in the graph ( P > 0.05). The Hosmer-Lemeshow goodness-of-fit test showed no statistically significant difference ( χ2 = 5.29, P = 0.582). The decision curve analysis indicated that when the risk of re-displacement exceeded 33.64% in older adult patients undergoing external fixation for distal radius fractures, the net benefit of intervening in these patients was maximized. Conclusions:Age, sex, presence of comminution, presence of bone resorption or necrosis, and the reasonableness of functional exercise are independent risk factors for re-displacement after external fixation treatment of distal radius fractures in older adult patients. The higher the score on the nomogram model, the greater the risk of fracture re-displacement in the patient.

Objective:To evaluate the clinical efficacy of proximal femoral reconstruction osteotomy (PFRO) in hip revision arthroplasty.Methods:A retrospective analysis was conducted of the 92 patients (93 hips) who had undergone PFRO in hip revision arthroplasty at Department of Orthopedics, The First Affiliated Hospital, University of Science and Technology of China from January 2019 to December 2023. The cohort included 50 males (51 hips) and 42 females (42 hips), with an age of (64.5±11.7) years and a body mass index of (23.7±2.9) kg/m 2. Surgical procedures were performed under general anesthesia via a posterolateral approach. Biologic prostheses were used in femoral reconstruction, and PFRO fragments repositioned and fixed using cerclage wires. The data collected were operative time, intraoperative blood loss, length of osteotomy fragments, healing at the osteotomy site, intraoperative and follow-up complications, as well as Harris hip score (HHS) and leg length discrepancy (LLD) at the last follow-up. Results:For this cohort, operative time was (174.9±45.6) minutes, intraoperative blood loss (594.6±206.6) mL, and length of osteotomy fragments (12.3±2.3) mm. The 92 patients were followed up for (35.8±12.3) months. For them, HHS improved from preoperative (38.3±8.5) points to (80.5±12.8) points at the last follow-up, and LLD decreased from preoperative (21.2±13.0) mm to 2.0(0.0, 5.0) mm at the last follow-up, showing significant differences ( P<0.05). The osteotomy sites healed in 89 cases (90 hips), with a displacement of the greater trochanter <5 mm; 3 cases (3 hips) experienced nonunion with wire loosening and a displacement of the greater trochanter >10 mm. The osteotomy fragment of the greater trochanter got fractured in 2 patients (2 hips) and a fracture of the medial cortex of the proximal femur occurred in 11 patients (11 hips), but follow-ups observed healing of all the fractures. One patient (1 hip) developed postoperative posterior dislocation of the hip which was treated conservatively. One patient (1 hip) developed postoperative periprosthetic infection which did not recur after twice of debridement followed by prosthetic revision of the proximal femoral tumor. Conclusion:In hip revision arthroplasty, as PFRO demonstrates a low incidence of fragment fractures of the greater trochanter and a high rate of healing at the osteotomy site, its short-term clinical outcomes are satisfactory.

Objective:To evaluate the clinical effect of bispherical augment in acetabular defects reconstruction in hip revision.Methods:This is a retrospective case series study. A retrospective analysis of 119 patients (124 hips) patients who underwent hip revision surgery and reconstructed with bispherical augment for acetabular bone defects from January 2019 to December 2023 was performed. There were 57 males (58 hips) and 62 females (66 hips), aged (65.0±11.8) years (range:40 to 102 years). The body mass index was (23.9±3.5) kg/m 2 (range:16.1 to 32.2 kg/m 2). Acetabular bone defects were typed as follows: 2 hips in Paprosky type ⅡA, 29 hips in type ⅡB, 34 hips in type ⅡC, 31 hips in type ⅢA, and 28 hips in type ⅢB, of which 9 patients (9 hips) were combined with pelvic discontinuity. Differences in Harris hip score (HHS) and lower limb discrepancy (LLD) were compared between preoperatively and final follow-up. The height of the hip center of rotation and the horizontal distance from the center of rotation to the teardrop were measured by radiographs before and after surgery, and prothesis stability and the occurrence of postoperative complications were evaluated. Data were compared using the paired sample t test. Results:All patients successfully completed the operation. The operation time was (167.0±53.4) minutes (range:90 to 380 minutes) and the intraoperative bleeding was (345.3±124.2) ml (range:100 to 1 200 ml). The height of the hip center of rotation decreased from (39.7±13.0) mm preoperatively to (21.8±7.1) mm postoperatively and the horizontal distance from the center of rotation to the teardrop increased from (34.0±10.1) mm preoperatively to (38.5±5.9) mm postoperatively, and the differences were statistically significant ( t=15.859, P<0.01; t=5.266, P<0.01). All the patients were followed up for (26.1±15.4) months (range:6 to 60 months). At the last follow-up, HHS improved from (35.2±10.0) points preoperatively to (85.5±9.5) points, and the difference was statistically significant ( t=50.723, P<0.01). LLD decreased from (2.1±1.1) cm preoperatively to (0.5±0.5) cm, and the difference was statistically significant ( t=13.767, P<0.01). All acetabular components were stable and free of displacement on imaging during follow-up. Three patients suffered dislocation and received closed reduction, all prosthesis were in good position during follow-up. No dislocation, loosening, fracture, recurrence of infection and vascular nerve injury occurred in other patients. Conclusion:Bispherical augment can effectively reconstruct acetabular bone defects, restore the hip center of rotation, and improve hip joint function scores at short and mid-term follow-up.

Objective:To compare the clinical efficacy of the anterior approach versus the posterolateral approach for total hip arthroplasty (THA) in treating residual high dislocation secondary to pyogenic hip arthritis, and to investigate the benefits of proximal femoral reconstruction osteotomy.Methods:A retrospective study was conducted on 45 patients who underwent THA combined with proximal femoral reconstruction osteotomy for high dislocation secondary to pyogenic hip arthritis at the First Affiliated Hospital of the University of Science and Technology of China from January 2017 to September 2022. Patients were categorized into two groups based on the surgical approach: 14 in the anterior approach group and 31 in the posterolateral approach group. We analyzed surgical duration, intraoperative blood loss, postoperative visual analogue scale (VAS) scores for lateral knee pain after knee extension, postoperative limb lengthening, Harris hip scores, and complications. Radiographic assessments included anteversion and abduction angles of the acetabular cup, hip abductor muscle lever arm, hip-knee-ankle (HKA) angle of the affected side, osteotomy site bone healing rate, and prosthesis loosening.Results:The average follow-up period was 3.6±1.8 years (range, 1.0-6.7 years). The anterior approach group had a significantly longer surgical duration (141.4±21.0 min) compared to the posterolateral approach group (121.3±23.1 min). Intraoperative blood loss was significantly less in the anterior approach group (425.2±80.2 ml) compared to the posterolateral approach group (535.1±96.3 ml). The difference was statistically significant ( P<0.05). The VAS score for lateral knee pain after knee extension was significantly lower in the anterior approach group (3.2±0.8) than in the posterolateral approach group (5.7±1.1), the difference was statistically significant ( t=7.300, P<0.001). Postoperative limb lengthening was 5.0±1.5 cm in the anterior approach group and 4.5±1.4 cm in the posterolateral approach group, with no significant difference ( t=1.075, P=0.289). At the final follow-up, the Harris hip score was 86.2±5.0 in the anterior approach group and 82.5±6.8 in the posterolateral approach group, with no significant difference ( t=1.839, P=0.073). The acetabular anteversion angle, abduction angle, and HKA angle in the anterior approach group were 12.9°±5.8°, 42.6°±6.2°, and 179.8°±1.4°, respectively, while in the posterolateral approach group they were 14.5°±7.0°, 44.2°±3.1°, and 178.8°±2.1°, respectively. The differences between the groups were not statistically significant ( P>0.05). The hip abductor muscle lever arm was 5.6±0.7 cm on the surgical side compared to 5.9±0.6 cm on the healthy side, with no significant difference ( t=1.916, P=0.059). All patients achieved bone healing at the osteotomy site by the final follow-up. One patient in the anterior approach group experienced femoral prosthesis subsidence but did not require femoral revision. Two patients in the posterolateral approach group experienced hip dislocation, both of which were managed with intravenous anesthesia and closed reduction. Conclusion:The anterior approach for THA combined with proximal femoral reconstruction osteotomy yields better clinical outcomes compared to the posterolateral approach, including reduced intraoperative blood loss, decreased lateral knee pain, and a lower rate of dislocation. Proximal femoral reconstruction osteotomy effectively restores the hip abductor muscle lever arm with a high rate of osteotomy site healing.

Objective:To evaluate the clinical effect of bispherical augment in acetabular defects reconstruction in hip revision.Methods:This is a retrospective case series study. A retrospective analysis of 119 patients (124 hips) patients who underwent hip revision surgery and reconstructed with bispherical augment for acetabular bone defects from January 2019 to December 2023 was performed. There were 57 males (58 hips) and 62 females (66 hips), aged (65.0±11.8) years (range:40 to 102 years). The body mass index was (23.9±3.5) kg/m 2 (range:16.1 to 32.2 kg/m 2). Acetabular bone defects were typed as follows: 2 hips in Paprosky type ⅡA, 29 hips in type ⅡB, 34 hips in type ⅡC, 31 hips in type ⅢA, and 28 hips in type ⅢB, of which 9 patients (9 hips) were combined with pelvic discontinuity. Differences in Harris hip score (HHS) and lower limb discrepancy (LLD) were compared between preoperatively and final follow-up. The height of the hip center of rotation and the horizontal distance from the center of rotation to the teardrop were measured by radiographs before and after surgery, and prothesis stability and the occurrence of postoperative complications were evaluated. Data were compared using the paired sample t test. Results:All patients successfully completed the operation. The operation time was (167.0±53.4) minutes (range:90 to 380 minutes) and the intraoperative bleeding was (345.3±124.2) ml (range:100 to 1 200 ml). The height of the hip center of rotation decreased from (39.7±13.0) mm preoperatively to (21.8±7.1) mm postoperatively and the horizontal distance from the center of rotation to the teardrop increased from (34.0±10.1) mm preoperatively to (38.5±5.9) mm postoperatively, and the differences were statistically significant ( t=15.859, P<0.01; t=5.266, P<0.01). All the patients were followed up for (26.1±15.4) months (range:6 to 60 months). At the last follow-up, HHS improved from (35.2±10.0) points preoperatively to (85.5±9.5) points, and the difference was statistically significant ( t=50.723, P<0.01). LLD decreased from (2.1±1.1) cm preoperatively to (0.5±0.5) cm, and the difference was statistically significant ( t=13.767, P<0.01). All acetabular components were stable and free of displacement on imaging during follow-up. Three patients suffered dislocation and received closed reduction, all prosthesis were in good position during follow-up. No dislocation, loosening, fracture, recurrence of infection and vascular nerve injury occurred in other patients. Conclusion:Bispherical augment can effectively reconstruct acetabular bone defects, restore the hip center of rotation, and improve hip joint function scores at short and mid-term follow-up.

Objective:To combine micro-course and flipped classroom, integrate the application of online WeChat group and teaching video, build a new teaching framework, and seek the application of flipped classroom based on "micro-course" in clinical skills training of general anesthesia and tracheal intubation for medical students.Methods:A total of 82 clinical medicine intern students of Batch 2015 and 2016 from Nnajing Drum Tower Hospital were selected as the research subjects to complete the internship (for two weeks). The teaching reform group (44 people) adopted the flipped classroom based on "micro-course"; the traditional group (38 people) adopted traditional teaching. Organized by the undergraduate teaching and research department, the number of tracheal intubation cases and the number of excellent scores were recorded during the two-week internship in anesthesia. After the rotation, a questionnaire survey was conducted to evaluate the mastery of endotracheal intubation operation and satisfaction with the teaching and training arranged by the department. SPSS 23.0 was used to conduct t test and non-parametric test. Results:The number of outstanding cases of tracheal intubation in the teaching reform group was higher than that in the traditional group, and the number of outstanding cases of tracheal intubation in girls was higher than that in boys, and the difference was statistically significant ( P<0.05). The self-assessed scores of the students' mastery of tracheal intubation and the satisfaction with clinical practice training in the teaching reform group were higher than those in the traditional group, and the difference was statistically significant ( P<0.05). Conclusion:Compared with traditional teaching, the flipped classroom based on "micro-course" has more advantages in the clinical skills training of medical tracheal intubation.

Psoriasis vulgaris is a recurrent inflammatory skin disease. A variety of factors, such as trauma and infection, can destroy the skin barrier function, thereby breaking the balance of immune homeostasis and tolerance, causing abnormalities in function and/or number of various immune-related cells in local skin, resulting in psoriasis-like skin changes such as abnormal proliferation of keratinocytes and excessive inflammatory reactions in skin lesions. Various immune cells in skin lesions can sense changes in the surrounding environment (autocrine or paracrine) through surface molecules, and then express and secrete a variety of inflammation-related factors; if maintenance mechanisms for immune homeostasis and tolerance become invalid, the positive feedback network of inflammation mediated by inflammation-related factors will be formed locally, leading to the occurrence of psoriasis vulgaris. This review summarizes research progress in the role of immune-related cells in skin lesions in the immunopathological mechanism of psoriasis vulgaris, especially innate immune cells such as γδT cells.