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

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.

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 correlation between hip muscle factors measured with CT imaging and recovery of independent mobility within 1 year after surgery in elderly patients with hip fractures.Methods:A prospective cohort study was conducted on the clinical data of 680 elderly patients with hip fractures admitted to Beijing Jishuitan Hospital of Capital Medical University from November 2018 to December 2019. The patients were assigned to dependent group and assistant group according to whether they regained pre-injury independent mobility within 1 year after surgery. Gender, age, body mass index, personal history, living habits, past diseases, Charlson comorbidity index, laboratory test indicators, fracture types, anesthesia types, surgical methods, rehabilitation training, time from injury to surgery, and hip muscle parameters in both groups were recorded. OsiriX software was employed in the measurement of the hip muscles to measure the muscle area and density of the gluteus maximus and gluteus medius/minimus on CT images, and the average values were calculated as hip muscle area and density. Then the variables of hip muscle area and density were converted seperately to gender-normalized Z-scores, and were divided into high-area group ( Z≥0) and low-area group ( Z<0), and high-density group ( Z≥0) and low-density group ( Z<0) respectively. Observable variables were primarily analyzed using univariate analysis between the independent group and assistant group. Those variables with statistically significant differences in the univariate analysis or would potentially affect mobility recovery according to previous researches although there were no statistical significance were included in a multivariate Logistic regression analysis. Three Logistic regression models were designed (Model 1 uncorrected, Model 2 corrected for gender, age and body mass index, Model 3 corrected for variables in Model 2 and other variables included after above-mentioned analysis) to analyze whether muscle parameters were risk factors for recovery of independent mobility. Additionally, generalized estimating equations were used for repeated measurement to analyze the correlation between hip muscle area and recovery of independent mobility after surgery. Results:Compared to the assistant group, the independent group were younger in age, with lower rate of living alone, being housebound, cognitive impairment, and Charlson comorbidity index, lower level of hemoglobin and albumin, higher rate of femoral neck fractures, lower rate of internal fixation, shorter time from injury to surgery, larger hip muscle area, and higher hip muscle density ( P<0.05 or 0.01). Multivariate Logistic regression analysis showed that, in the fully corrected Model 3, only hip muscle area remained significantly correlated with recovery of independent mobility ( P<0.05), while no significant difference was found between the high-density group and low-density group ( P>0.05). In the repeated measurement, patients in the high-area group were 1.84 times more likely to restore independent mobility than those in the low-area group ( OR=1.84, 95% CI 1.33, 2.53, P<0.01). Conclusions:Hip muscle area measured with CT imaging is closely correlated to the recovery of independent mobility within 1 year after surgery in elderly patients with hip fractures. Moreover, larger hip muscle area indicates a larger likelihood of recovery of independent mobility.

Objective:To investigate the genetic, clinical, and post-treatment characteristics of patients with glycogen storage disease type Ⅲ (GSD Ⅲ).Methods:A retrospective cohort analysis was performed on the genetic and clinical data of 26 cases with GSD Ⅲ who visited the Children's Hospital affiliated with Fudan University from June 2017 to December 2023. The patients were divided into non-missense variation and missense variation groups according to the types of mutation in the AGL gene.The correlation between genotype and phenotype was analyzed. All patients were treated with uncooked cornstarch after diagnosis. The changes before and after treatment were compared in patients who underwent more than twelve months of follow-up. A P value of <0.05 was used to denote statistical significance. Results:Among the 26 cases enrolled, 13 were female and 13 were male, and the median age of diagnosis was 28 (6 to 134) months. A total of thirty-five different types of AGL gene variation were detected, with c.1735+1G＞T (9/52, 17.3%) as the hotspot variation. The common clinical manifestations were elevated aminotransferases (26/26, 100%), hepatomegaly (25/26, 96.2%), fasting hypoglycemia (25/26, 96.2%), hyperketonemia (16/18, 88.9%), hypertriglyceridemia (TG) (20/26, 76.9%), elevated CK (16/25, 64.0%), and an abnormal electrocardiogram (12/16, 75.0%). Four cases (15.4%) had symptoms of myopathy at diagnosis. Liver biopsy was performed in eighteen cases, among whom 83.3% (15/18) had liver fibrosis≥S2. The number of cases with elevated levels of CK ( P＝0.031) and ALT ( P＝0.038)was pronounced in the non-missense variation group compared to that in the missense variation group. There were no statistically significant differences in age, height, liver size, degree of fibrosis, fasting blood glucose (Glu) and TG ( P>0.05). The median follow-up time of 14 cases was 40.5 (20-73) months, with improvement in body stature, reduced liver size, decreased ALT and TG, and improved Glu. However, four (28.6%) cases had new myopathy symptoms with raised CK ( P<0.05) and with advancing age, increased ALT diminished while CK level elevated ( P<0.05). Conclusions:The common clinical manifestations at the early stage of the GSD Ⅲdiagnosis are elevated aminotransferases, hepatomegaly, fasting hypoglycemia, hyperketonemia, high triglycerides, elevated CK, and fibrotic liver in China. Myopathy symptoms may arise following uncooked cornstarch treatment; however, there is significant improvement in height, liver-related, and metabolic parameters.

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.