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 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.

Neuroplastin 65(NP65) is a glycoprotein class with selective expression in neurons. It is extensively expressed in the synaptic membrane of the central nervous system, and plays a fundamental role in cell adhesion and intercellular communication. In comparison to other cell adhesion molecules, the discovery of NP65 is relatively late and researches about this molecule are still in development. Further exploration and study of the pathophysiological mechanism involved in NP65 are needed. It has been confirmed that NP65 plays a pivotal role in neural activities, including regulation of synaptic formation and maintenance, modulation of synaptic plasticity, facilitation of neuronal development, and contribution to the pathogenesis of various diseases. Thus, NP65 could potentially serve as a crucial target for modulating the growth and operation of the nervous system. This paper provides a comprehensive review of the structure, distribution, function, and involvement in both physiological and pathological processes of NP65. Additionally, the future research direction for NP65 is proposed, with the aim of enhancing our understanding of its function, revealing its mechanism of action in diseases, and providing a theoretical basis for the development of related clinical applications.

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 compare the efficacies of 3D printed guide plate assisted positioning and C-arm X-ray machine fluoroscopic positioning for femoral tunnel reconstruction of medial patellofemoral ligament in treating recurrent patellofemoral dislocation.Methods:A retrospective cohort study was performed on the clinical data of 60 patients with recurrent patellar dislocation admitted to the First Affiliated Hospital of Kunming Medical University from January 2018 to December 2022. The patients included 29 males and 31 females, with age range of 14-40 years [(28.6±7.6)years]. The 3D printed guide plate was used to locate the femoral tunnel in 30 patients for medial patellofemoral ligament reconstruction (3D guide group), and C-arm X-ray machine was used for another 30 patients (conventional group). (1) CT data of the knee joint were collected before surgery and at 7 days after surgery. Mimics 19.0 software was introduced to measure the distance between the center of femoral tunnel and Sch?ttle point after surgery. (2) Knee Lysholm score and Kujala score were used to evaluate the knee function before and at 3, 6, 9 and 12 months after surgery. (3) At the same time points, Opti-Knee TM 3D knee kinematics analysis system was used to collect the forward and backward displacement, up and down displacement, internal and external displacement, internal and external flipping angle, internal and external rotation angle, and flexion and extension angle of the affected knee joint. The range of each freedom degree was calculated and 6 freedom degree items of 30 healthy people were subjected to knee kinematics analysis. Results:All patients were followed up for 12-15 months [(12.3±0.7)months]. (1) The distance between the center of femoral tunnel and Sch?ttle point in the 3D guide group was (5.5±2.3)mm, smaller than that in the conventional group [(7.6±2.5)mm] ( P<0.01). (2) The Lysholm score and Kujala score of the 3D guide group and conventional gruop gradually increased after surgery (all P<0.01). There were no significant differences in the Lysholm score or Kujala score between the 3D guide group and conventional gruop before surgery and at 12 months after surgery (all P>0.05). At 3, 6 and 9 months after surgery, the Lysholm score of the 3D guide group [(70.4±4.5)points, (86.4±3.1)points, (91.2±3.2)points] and Kujala score [(74.2±5.3)points, (80.9±3.5)points, (85.2±3.2)points] were higher than those of the conventional group [Lysholm score: (67.3±5.2)points, (81.8±2.5)points, (86.2±1.9)points; Kujala score: (69.8±5.2)points, (77.6±2.1)points, (82.7±2.6)points] ( P<0.05 or 0.01). (3) Before surgery, the forward and backward displacement in the 3D guide group and conventional group [(0.6±0.1)cm, (0.6±0.2)cm], up and down displacement [(0.5±0.1)cm, (0.6±0.0)cm], internal and external displacement [(0.7±0.1)cm, (0.6±0.2)cm], and flexion and extension angle [(50.6±10.3)°, (51.6±8.5)°] were less than those in the healthy controls [(1.6±0.3)cm, (1.7±0.5)cm, (1.0±0.4)cm, (63.2±5.1)°] (all P<0.05), while the internal and external flipping angle [(17.5±4.0)°, (17.1±3.8)°] and internal and external rotation angle [(17.9±1.9)°, (17.5±1.5)°] were greater than those in the healthy controls [(11.8±3.6)°, (15.8±4.9)°] (all P<0.05). At other time points, the results of front and back displacement, up and down displacement, internal and external displacement, internal and external rotation angle in the 3D guide group and conventional group were not significantly different compared with the healthy controls (all P>0.05). The flexion and extension angle in the 3D guide group and conventional gruop were smaller than those in the healthy controls at 3 months after surgery (all P<0.05). At 6 and 9 months after surgery, the flexion and extension angle in the conventional group [(55.0±3.7)°, (57.7±4.8)°] were smaller than those in the healthy controls [(63.2±5.1)°, (63.2±5.1)°] (all P<0.05), but no significant difference was found between the 3D guide group [(61.0±4.8)°, (61.8±4.9)°] and the healthy controls (all P>0.05). The flexion and extension angle in the 3D guide group and conventional gruop was similar with that in the healthy controls at 12 months after surgery (all P>0.05). Conclusions:Compared with the C-arm X-ray machine, the 3D printed guide plate assisted positioning of femoral tunnel is more simple and accurate for the medial patellofemoral ligament reconstruction in treating recurrent patellofemoral dislocation, together with better early knee function recovery, better satisfaction of the patients, and better and faster restoration of the flexion and extension angle of knee joint kinematic function.

Postoperative delirium(POD),a common surgical complication,refers to the acute and fluctuating disturbance in attention and awareness after surgery,which seriously affects the recovery and is one of the predictors of poor prognosis of patients.At present,preoperative anxiety is common in periopera-tive patients.As the independent risk factors for POD,preoperative anxiety plays an important role in the occurrence and development of POD.Taking active and reasonable intervention measures for patients with preoperative anxiety may effectively reduce the occurrence of POD.This paper reviews the effects of preoper-ative anxiety on POD,focusing on its mechanism and prevention methods,in order to explore the relation-ship between preoperative anxiety and POD,which might provide new ideas for the clinic.

Objective:To explore the nursing work items and the technical difficulty in post anesthesia care unit, so as to provide the basis for accurate calculation of anesthesia nursing workload and reasonable matching of human resources.Methods:The primary and secondary indicators of the nursing working system in post anesthesia care unit were determined through the literature review and group discussion. Delphi method was used to revise the indicators and evaluate the importance and difficulty degree of the indicators. Finally, analytic hierarchy process and linear weighted sum method were used to calculate the weight value and difficulty coefficient of each index.Results:The positive coefficients of the experts in the two rounds were 100.00%, the authority coefficients of the experts were 0.90 and 0.96, the variation coefficients ranged from 0.000 to 0.342 and 0.042 to 0.307, and the Kendall coefficients were 0.239 and 0.273 (both P<0.01). The evaluation index system of the difficulty of nursing work in post anesthesia care unit was finally composed of 10 primary indicators and 85 secondary indicators. The weight of the primary index ranged from 0.016 4 to 0.186 4, and the weight of the secondary index ranged from 0.000 8 to 0.064 3. The standardized difficulty coefficient of the secondary index ranged from 1.02 to 1.59. Conclusions:The evaluation index system of the difficulty of nursing work items in post anesthesia care unit was comprehensive and the difficulty coefficient was in line with the actual clinical work in this study, which provides reference for the follow-up scientific calculation of nursing workload and human resources matching in post anesthesia care unit.