Human naïve pluripotent stem cells (PSCs) hold great promise for embryonic development studies. Existing induction and culture strategies for these cells, heavily dependent on MEK inhibitors, lead to widespread DNA hypomethylation, aberrant imprinting loss, and genomic instability during extended culture. Here, employing high-content analysis alongside a bifluorescence reporter system indicative of human naïve pluripotency, we screened over 1,600 chemicals and identified seven promising candidates. From these, we developed four optimized media-LAY, LADY, LUDY, and LKPY-that effectively induce and sustain PSCs in the naïve state. Notably, cells reset or cultured in these media, especially in the LAY system, demonstrate improved genome-wide DNA methylation status closely resembling that of pre-implantation counterparts, with partially restored imprinting and significantly enhanced genomic stability. Overall, our study contributes advancements to naïve pluripotency induction and long-term maintenance, providing insights for further applications of naïve PSCs.
Humans ; DNA Methylation/drug effects* ; Genomic Instability ; Pluripotent Stem Cells/metabolism* ; Cell Culture Techniques/methods* ; Cells, Cultured

Objective:To evaluate the feasibility and efficacy of our self-designed intelligent robot-assisted reduction system for fresh subtrochanteric fractures of the femur.Methods:A retrospective cohort study was conducted to include 10 patients with fresh subtrochanteric fracture of the femur who had been admitted to Department of Orthopedic Trauma, Beijing Jishuitan Hospital from January 2024 to July 2024. There were 7 males and 3 females with an age of (45.0±14.3) years and an interval from injury to surgery of (7.9±3.7) d. All the patients were treated by minimally invasive reduction which was assisted by our self-designed intelligent robot, and internal fixation with intramedullary nails. The operation duration, intraoperative reduction duration, intraoperative blood loss, and intraoperative fluoroscopy frequency were recorded. The reduction effect was evaluated by calculating the differences between preoperative planning and postoperative CT reconstruction (i.e., the differences in femoral shaft length and in rotation angle). The hip functional recovery was assessed by Harris hip function Scoring.Results:The mean operation time was 200.0 (161.3, 217.5) min, the reduction time (83.0±35.5) min, the intraoperative blood loss (290.0±110.1) mL, and the intraoperative fluoroscopy 18.5 (9.0, 19.3) times. In all patients, the difference in femoral shaft length was (2.4±1.4) mm, and the difference in rotation angle 5.1°±3.0°. All patients were followed up for (8.2±2.0)months. All the fractures got united at the last follow-up. Their Harris hip function score was (83.3±4.1) points.Conclusion:Our self-designed intelligent robot-assisted reduction system is feasible and effective in the surgery of fresh subtrochanteric fracture of the femur, because the robot system can complete the autonomous planning of reduction approaches before surgery and assist fracture reduction under real-time monitoring with three-dimensional images, leading to fine outcomes.

Objective:To investigate how age and nail-tract volumetric bone mineral density (vBMD) are associated with postoperative mechanical performance of proximal femoral nail anti-rotation (PFNA-Ⅱ) fixation for geriatric intertrochanteric fractures using a finite-element analysis.Methods:Fifteen elderly patients with intertrochanteric fracture of the femur were selected for this study. They were 11 females and 4 males and divided into 5 groups based on their ages ( n=3): 55-year-old, 65-year-old, 75-year-old, 85-year-old, and 95-year-old groups. After three-dimensional models of the proximal femur were constructed using the preoperative CT data of their healthy contralateral hip, 31-A1.2 fractures of the AO/OTA type were created and PFNA-Ⅱ fixations simulated. Two loading schemes were created: graded quasi-static axial loads (700 N, 1,400 N, 2,100 N, and 2,800 N) were applied to compute equivalent plastic strain volumes in the femoral head region; displacement-controlled loading was applied to failure to derive load-displacement curves for stiffness and the maximum failure load. Nail-tract vBMD and regional hip vBMDs were measured by quantitative CT. Pearson correlation analysis was conducted to investigate the associations of age and nail-tract vBMD with the aforementioned mechanical indicators. Results:Under the same load, compared with the 55-year-old, 65-year-old, and 75-year-old groups, the plastic strain unit volumes of the fracture models in the 85-year-old and 95-year-old groups increased significantly. Under a load of 700 N, no plastic strain was observed in the fracture models in the 55-year-old, 65-year-old, and 75-year-old groups, while an average plastic strain of approximately 50 mm 3 was observed in the fracture models in the 85-year-old group. Under a load of 2,800 N, the high strain areas in the fracture models in the 85-year-old and 95-year-old groups were mainly concentrated at the tip of the head nail and the junction between the head nail and the main nail. Load-displacement curves showed a marked reduction in the failure load in patients aged ≥85 years. Under loads of 1,400 N, 2,100 N, and 2,800 N, there was a strong association between the nail-tract vBMD and the volume of the plastic strain unit ( r=-0.82, -0.88, -0.89, respectively), which was stronger than those for total-hip vBMD. Conclusions:Finite-element analysis indicates that age and nail-tract vBMD are closely related to local plastic strain and overall stiffness of the proximal femur after PFNA-Ⅱ fixation for the geriatric intertrochanteric fractures. Patients aged ≥85 years old are more prone to plastic yielding, which compromises fixation stability.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To evaluate the feasibility and efficacy of our self-designed intelligent robot-assisted reduction system for fresh subtrochanteric fractures of the femur.Methods:A retrospective cohort study was conducted to include 10 patients with fresh subtrochanteric fracture of the femur who had been admitted to Department of Orthopedic Trauma, Beijing Jishuitan Hospital from January 2024 to July 2024. There were 7 males and 3 females with an age of (45.0±14.3) years and an interval from injury to surgery of (7.9±3.7) d. All the patients were treated by minimally invasive reduction which was assisted by our self-designed intelligent robot, and internal fixation with intramedullary nails. The operation duration, intraoperative reduction duration, intraoperative blood loss, and intraoperative fluoroscopy frequency were recorded. The reduction effect was evaluated by calculating the differences between preoperative planning and postoperative CT reconstruction (i.e., the differences in femoral shaft length and in rotation angle). The hip functional recovery was assessed by Harris hip function Scoring.Results:The mean operation time was 200.0 (161.3, 217.5) min, the reduction time (83.0±35.5) min, the intraoperative blood loss (290.0±110.1) mL, and the intraoperative fluoroscopy 18.5 (9.0, 19.3) times. In all patients, the difference in femoral shaft length was (2.4±1.4) mm, and the difference in rotation angle 5.1°±3.0°. All patients were followed up for (8.2±2.0)months. All the fractures got united at the last follow-up. Their Harris hip function score was (83.3±4.1) points.Conclusion:Our self-designed intelligent robot-assisted reduction system is feasible and effective in the surgery of fresh subtrochanteric fracture of the femur, because the robot system can complete the autonomous planning of reduction approaches before surgery and assist fracture reduction under real-time monitoring with three-dimensional images, leading to fine outcomes.

Objective:To investigate how age and nail-tract volumetric bone mineral density (vBMD) are associated with postoperative mechanical performance of proximal femoral nail anti-rotation (PFNA-Ⅱ) fixation for geriatric intertrochanteric fractures using a finite-element analysis.Methods:Fifteen elderly patients with intertrochanteric fracture of the femur were selected for this study. They were 11 females and 4 males and divided into 5 groups based on their ages ( n=3): 55-year-old, 65-year-old, 75-year-old, 85-year-old, and 95-year-old groups. After three-dimensional models of the proximal femur were constructed using the preoperative CT data of their healthy contralateral hip, 31-A1.2 fractures of the AO/OTA type were created and PFNA-Ⅱ fixations simulated. Two loading schemes were created: graded quasi-static axial loads (700 N, 1,400 N, 2,100 N, and 2,800 N) were applied to compute equivalent plastic strain volumes in the femoral head region; displacement-controlled loading was applied to failure to derive load-displacement curves for stiffness and the maximum failure load. Nail-tract vBMD and regional hip vBMDs were measured by quantitative CT. Pearson correlation analysis was conducted to investigate the associations of age and nail-tract vBMD with the aforementioned mechanical indicators. Results:Under the same load, compared with the 55-year-old, 65-year-old, and 75-year-old groups, the plastic strain unit volumes of the fracture models in the 85-year-old and 95-year-old groups increased significantly. Under a load of 700 N, no plastic strain was observed in the fracture models in the 55-year-old, 65-year-old, and 75-year-old groups, while an average plastic strain of approximately 50 mm 3 was observed in the fracture models in the 85-year-old group. Under a load of 2,800 N, the high strain areas in the fracture models in the 85-year-old and 95-year-old groups were mainly concentrated at the tip of the head nail and the junction between the head nail and the main nail. Load-displacement curves showed a marked reduction in the failure load in patients aged ≥85 years. Under loads of 1,400 N, 2,100 N, and 2,800 N, there was a strong association between the nail-tract vBMD and the volume of the plastic strain unit ( r=-0.82, -0.88, -0.89, respectively), which was stronger than those for total-hip vBMD. Conclusions:Finite-element analysis indicates that age and nail-tract vBMD are closely related to local plastic strain and overall stiffness of the proximal femur after PFNA-Ⅱ fixation for the geriatric intertrochanteric fractures. Patients aged ≥85 years old are more prone to plastic yielding, which compromises fixation stability.

Objective To explore the therapeutic effect of mesorectal excision in gasless transaxillary endoscopic thyroidectomy.Methods Clinical data of 75 patients who underwent gasless unilateral transaxillary endoscopic thyroidectomy from May 2020 to November 2022 were retrospectively analyzed.A total of 40 cases were treated with mesorectal excision(observation group),and 35 cases were treated with thyroid resection followed with central lymph node resection(control group).The operation time,intraoperative blood loss,postoperative hospital stay,number of lymph nodes dissected,and postoperative complications were compared between the two groups.Results All the patients successfully completed the operation.As compared with the control group,the observation group had shorter operation time[(91.8±19.7)min vs.(110.4±19.3)min,t =-4.133,P =0.000]and more lymph nodes dissected[(6.5±2.5)vs.(4.6±2.0),t = 3.610,P = 0.001].There were no statistically significant differences between the two groups in the amount of intraoperative bleeding,recurrent laryngeal nerve injury,and the postoperative hospital stay.There was no hypoparathyroidism,postoperative bleeding,or wound infection in both groups.Conclusion Mesorectal excision is safe and feasible in endoscopic thyroidectomy via axillary approach,with more thorough lymph node dissection in the central region and better protection of recurrent laryngeal nerve.

Objective To explore the learning curve of endoscopic mesothyroid excision via gasless axillary approach.Methods Clinical data of 44 patients who underwent endoscopic mesothyroid excision via gasless axillary approach between May 2020 and December 2022 by the same surgical team were retrospectively analyzed.Taking operation time as index,the learning curve of the operation was studied with the cumulative sum method(CUSUM).The cut-off value of the learning curve was regarded as the dividing line of different stages.The general data,operation time,intraoperative blood loss,hospital stay,number of lymph node dissection,and postoperative complications were compared between the different phases of the learning curve.Results The operations were successfully completed in all the 44 patients without conversion to open surgery.The cumulative sum fitting curve reached the top at the 21st case,which was used as the boundary to divide the learning curve into learning improvement stage and mature stable period.There was no statistically significant difference between the two stages in general data(P>0.05).The operation time in the learning improvement stage was significantly longer than in the mature stable period[(124.5±9.9)min vs.(82.0±8.8)min,t =15.166,P =0.000].The incidence of postoperative sternocleidomastoid muscle swelling and stiffness in patients in the learning improvement stage was higher than that in the mature stable period,but the difference was not statistically significant[6 cases(28.6%)vs.1 case(4.3%),χ2 =3.174,P =0.075].There was no significant difference between the two groups in terms of intraoperative bleeding,hospital stay,number of lymph node dissection,and other postoperative complications(all P>0.05).Conclusion To proficiently master the endoscopic mesothyroid excision via the gasless axillary approach,21 cases need to be completed.

Radical cystectomy combined with pelvic lymph node dissection is the standard procedure for the treatment of muscle invasive bladder cancer and complex non-muscle invasive bladder cancer.Our department has routinely carried out laparoscopic radical cystectomy(ELRC)through the extraperitoneal approach in 340 cases.This article summarizes the establishment of the peritoneal space,the expansion of the peritoneal space,the operation steps of bladder resection and lymph node dissection through the peritoneal channel,and how to shorten the operation time and reduce the difficulty of the operation.During the surgery,the bladder is removed periperitoneally without destroying the peritoneum to preserve the functions of peritoneum support,secretion,protection and lubrication,which has little impact on the abdominal organs,reduces the incidence of complications,and provides favorable conditions for subsequent treatment.