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 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.

OBJECTIVE: To explore the relationship between serum mannose-binding lectin( MBL) and T helper cell 17( Th17)/regulatory T cells( Treg) balance in patients with silicosis. METHODS: A total of 101 male patients with silicosis were selected in silicosis group and 62 health individuals in control group using the cross-sectional study. The level of serum MBL was measured by enzyme linked immunosorbent assay. The ratio of Th17/Treg was recorded by flow cytometry.The relative expression of retinoid-related orphan nuclear receptor γt( RORγt) and forkhead box 3( Foxp3) mRNA in peripheral blood mononuclear cell were tested by real-time polymerase chain reaction method. RESULTS: The level of serum MBL in silicosis group was higher than that of control group( P < 0. 01). The ratio of Th17 cells and the relative expression of RORγt mRNA increased in silicosis group( P < 0. 05),while the ratio of Treg cells and the relative expression of Foxp3 mRNA decreased in silicosis group( P < 0. 05) compared to the control group. The level of serum MBL had negative correlation with forced expiratory volume in the first second,forced vital capacity and forced expiratory flow( P < 0. 05) in patients with stage Ⅰ and Ⅱ silicosis. Meanwhile,the level of serum MBL had negative correlation with Th17 ratio and RORγt mRNA relative expression( P < 0. 05),and positive correlation with Treg ratio and Foxp3 mRNA relative expression( P < 0. 05). CONCLUSION: MBL might participate in the development of silicosis through regulating the balance of Th17/Treg cells.

Objective:To observe the effect of clinical pharmacists on the pain education in the patients with fracture. Methods:A total of 122 fracture patients with ASAⅠ/Ⅱaged 18-80 years were randomly divided into the intervention group (n=61) and the control group(n=61). The control group received the conventional orthopedic treatment..Flurbiprofen was injected for the postopera-tive analgesia,and if the pain VAS score was above 6,pethidine solution was given at the dose of 50 mg immediately. Based on the conventional treatment,the patients in the intervention group were educated by clinical pharmacist one day before the surgery,and then strengthened education was given after the surgery.The pain VAS score,and sleeping quality at 6h,24h,48h and 72h and satisfaction of pain management were compared between the groups.Results:The VAS score of the intervention group was significantly lower than that of the control group at 6 h,24 h,48 h and 72 h after the operation (P<0.05). The scores of sleeping quality in the intervention group at 6 h and 24 h after the operation were higher than those in the control group (P<0.05). The scores of patients' satisfaction were significantly higher in the intervention group than those of the control group (P<0.05). Conclusion: The clinical pharmacist's pain education can improve the degree of pain control and sleeping quality,increase the patients' satisfaction with pain control to a cer-tain extent.

Objective:To ascertain whether the immune complexes (ICs) formed by Dengue virus 1 non-structure protein 1 (DENV1 NS1)and its IgG antibodies could mediate passive systemic anaphylaxis (PSA) and to explain the pathogenesis of Dengue hemorrhagic fever or Dengue shock syndrome (DHF/DSS).Methods:The monoclonal antibodies (mAbs) or mAb cocktails from 20 IgG mAbs of DENV1 NS1 prepared in this lab were screened to initiate PSA and passive cutaneous anaphylaxis (PCA) in mice.Meanwhile, the effects of GdCl3 and platelet activating factor ( PAF) antagonist CV-3988 on PSA induced by the NS1-IgG ICs were observed.Results:Two groups of monoclonal antibody cocktails with purified NS 1 were proved to be capable of provoking PCA and PSA in mice,whereas the other mAbs or mAb cocktails could be not .The murine PSA initiated by NS1-IgG(5D25+3B1) ICs could be sig-nificantly inhibited by in vivo treatment with GdCl3 or PAF antagonist CV-3988.Conclusion: The NS1-IgG ICs formed with DENV1 NS1 and IgG mAb cocktails can mediate PSA and PCA ,but not all of ICs formed by DENV 1 NS1 mAbs or mAb cocktails with DENV 1 NS1 can induce PSA ,indicating that it may be related to the special epitopes of DENV 1 NS1.The monocyte/macrophages and PAF may be as major effector cells and the major mediator for PSA induced by NS 1-IgG ICs,respectively.

Objective To observe the clinical efficacy of noninvasive ventilation (NIV) on the treatment of acute respiratory distress syndrome (ARDS) caused by severe pneumonia after kidney transplantation. Methods The clinical data of 17 patients who were diagnosed as ARDS caused by severe pneumonia after kidney transplantation and treated with NIV in Sichuan Provincial People's Hospital from January 1st, 2014 to June 1st, 2016 were collected and retrospectively analyzed. According to the result of NIV treatment, the patients were divided into NIV success group (n = 9) and NIV failure group (n = 8). The differences in gender, age, underlying diseases, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, laboratory parameters on the day when ARDS was diagnosed, daily immunosuppressive dosage, NIV support condition and duration, arterial blood gas analysis and adverse reactions between the two groups were compared. Receiver operating characteristic curve (ROC) was plotted, and the predictive value of each parameters for NIV results was evaluated. Results The two groups were similar in gender, age, and underlying diseases. The APACHEⅡ score, serum levels of procalcitonin (PCT) and brain natriuretic peptide (BNP), serum creatinine (SCr), daily tacrolimus dose, and NIV support condition in NIV failure group were significantly higher than those in NIV success group [APACHEⅡscore: 16.7±5.7 vs. 10.3±2.1, PCT (μg/L): 32.8 (1.2, 187.7) vs. 0.3 (0.1, 2.9), BNP (ng/L): 832.4 (263.7, 1 180.2) vs. 157.0 (33.9, 218.5), SCr (μmol/L): 284.8 (90.5, 474.2) vs. 186.6 (76.7, 206.3), daily tacrolimus dose (mg): 3.6 (3.1, 4.0) vs. 2.6 (2.0, 3.5), inspiratory positive airway pressure (IPAP,cmH2O, 1 cmH2O = 0.098 kPa): 14.8±4.1 vs. 9.0±1.1, expiratory positive airway pressure (EPAP, cmH2O): 7.6±1.8 vs. 4.7±0.8, fraction of inspired oxygen (FiO2): 0.75±0.25 vs. 0.43±0.06, all P < 0.05], and the oxygenation index (PaO2/FiO2) after treatment was significantly lower than that of NIV success group [mmHg (1 mmHg = 0.133 kPa):107.4±65.2 vs. 268.7±98.8, P < 0.05]. There was no significant difference in albumin (Alb), white blood cell count (WBC), daily mycophenolate mofetil dose, use of glucocorticold, NIV duration, pH value, arterial partial pressure of carbon dioxide (PaCO2), or the incidence of sputum drainage disorder or pneumothorax between the two groups. ROC curve analysis showed that the predictive value of APACHEⅡ score, serum PCT and BNP levels, tacrolimus daily dosage and PaO2/FiO2changes after NIV treatment for the efficacy of NIV was high, the area under the ROC curve (AUC) was 0.813, 0.778, 0.903, 0.778, 0.764, respectively; when the cut-off value of APACHEⅡ score was 16.0, PCT was 4.1 μg/L, BNP was 180.5 ng/L, tacrolimus daily dosage was 2.5 mg, PaO2/FiO2increased 49.5 mmHg, the sensitivity was 87.5%, 75.2%, 87.5%, 87.5% and 75.0%, respectively, and the specificity was 77.8%, 66.7%, 88.9%, 74.4%, 88.9%, respectively. However, SCr was not sensitive to the NIV effect prediction. Conclusions NIV in the treatment of ARDS caused by severe pneumonia after kidney transplantation has a certain value. The fewer tacrolimus daily dosage, the lower APACHE Ⅱ score and levels of PCT and BNP, the more effective promotion of PaO2/FiO2after NIV treatment, and the better curative effect is suggested.